id
stringlengths 40
40
| source
stringclasses 9
values | title
stringlengths 2
345
| clean_text
stringlengths 35
1.63M
| raw_text
stringlengths 4
1.63M
| url
stringlengths 4
498
| overview
stringlengths 0
10k
|
|---|---|---|---|---|---|---|
bdbf80120ff282d682a8a56a7ccea177c4132e3c | wikidoc | Arkopal | Arkopal
Arkopal is a non-ionic surfactant consisting of a hydrophobic 9-carbon atom alkyl tail connected to a phenol molecule, that is in turn connected to an ethyleneglycol chain. The length of this ethylene glycol chain is given by the code for the amphiphile Arkopal-N60 means, for example, that there are on average 6 ethylene glycol units connected to the phenol. The average means there are molecules with more and with less ethylene glycols, this is due to the chemical synthesis. therefore, it has a polydispersity. It is an industrial surfactant and widely used.
names: ethoxylated nonylphenol; (nonylphenoxy)polyethyleneoxide
CAS-number: 9016-45-9
molecular weight: variable (oligomeric)
Toxicity (LD50, rat, oral) 4 g/kg
# Uses
It is used as additive in crop protection, lowering surface tension and thereby increasing the effectiveness of the pesticide, and it is used as detergent, for example in oil drilling fluids. | Arkopal
Arkopal is a non-ionic surfactant consisting of a hydrophobic 9-carbon atom alkyl tail connected to a phenol molecule, that is in turn connected to an ethyleneglycol chain.[1] The length of this ethylene glycol chain is given by the code for the amphiphile Arkopal-N60 means, for example, that there are on average 6 ethylene glycol units connected to the phenol. The average means there are molecules with more and with less ethylene glycols, this is due to the chemical synthesis. therefore, it has a polydispersity. It is an industrial surfactant and widely used.
names: ethoxylated nonylphenol; (nonylphenoxy)polyethyleneoxide
CAS-number: 9016-45-9
molecular weight: variable (oligomeric)
Toxicity (LD50, rat, oral) 4 g/kg
# Uses
It is used as additive in crop protection, lowering surface tension and thereby increasing the effectiveness of the pesticide, and it is used as detergent, for example in oil drilling fluids. | https://www.wikidoc.org/index.php/Arkopal | |
1170483d90a5621ed4b2875201deb0d2727924c7 | wikidoc | Choline | Choline
# Overview
Choline is an organic compound, classified as an essential nutrient and usually grouped within the Vitamin B complex. This natural amine is found in the lipids that make up cell membranes and in the neurotransmitter acetylcholine. Adequate intakes (AI) for this micronutrient of between 425 to 550 milligrams daily, for adults, have been established by the Food and Nutrition Board of the Institute of Medicine of the National Academy of Sciences.
# History
Choline was discovered by Andreas Strecker in 1864 and chemically synthesized in 1866. In 1998 choline was classified as an essential nutrient by the Food and Nutrition Board of the Institute of Medicine (U.S.A.).
# Chemistry
Choline is a quaternary saturated amine with the chemical formula: (CH3)3N+CH2CH2OHX−.
where X− is a counterion such as chloride (see choline chloride), hydroxide or tartrate.
# Physiology
Choline and its metabolites are needed for three main physiological purposes: structural integrity and signaling roles for cell membranes, cholinergic neurotransmission (acetylcholine synthesis), and as a major source for methyl groups via its metabolite, trimethylglycine (betaine) that participates in the S-adenosylmethionine synthesis pathways.
When choline is metabolized by the body, it may form trimethylamine, a compound with a fishy odor. Hence, when large amounts of choline are taken the person may suffer from a fishy body odor.
# Choline as a supplement
It is well established that supplements of methyl group transfer vitamins B6, B12, folic acid reduce the blood titer of homocysteine and prevent heart disease. Choline is a necessary source of methyl groups for methyl group transfer. Supplements of lecithin/choline by Central Soya scientists reduced heart disease in laboratory studies. The reduction in heart disease with lecithin supplements may however relate more to the cholesterol carrying capacity of lecithin than to the methyl group transfer role of choline.Template:Specify
Choline supplements are often taken as a form of 'smart drug' or nootropic, due to the the role that the neurotransmitter acetylcholine plays in various cognition systems within the brain. Choline is a chemical precursor or "building block" needed to produce the neurotransmitter acetylcholine, and research suggests that memory, intelligence and mood are mediated at least in part by acetylcholine metabolism in the brain. The efficacy, benefits and negative side effects of these supplements is a topic of continuing debate; research in the New England Journal of Medicine has suggested that choline supplements could have a detrimental effect on individuals who suffer from clinical depression or bipolar disorder, who seem to be hypersensitive to acetylcholine.
The Food and Drug Administration (FDA) requires that infant formula be made from cow's milk containing choline.
Due to its role in lipid metabolism, choline has also found its way into nutritional supplements which claim to reduce body fat; but there is little or no evidence to prove that it has any effect on reducing excess body fat or that taking high amounts of choline will increase the rate at which fat is metabolised.
# Sources
The foods richest in phosphatidylcholine — the major delivery form of choline — are egg yolks, soy and cooked beef, chicken, veal and turkey livers. Many foods contain trace amounts of free choline, even iceberg lettuce. To what extent these trace forms are usable by human digestion is still debated. In 2004, the USDA released its first database of the choline content in common foods.
The most often available choline dietary supplement is lecithin, derived from soy or egg yolks, often used as a food additive. Phosphatidylcholine is also available as a supplement, in pill or powder form. Supplementary Choline is also available as Choline Chloride, which comes as a liquid due to its hydrophilic properties. Choline chloride is sometimes preferred as a supplement because phosphatidylcholine can have gastrointestinal side effects.
# Additional images
- Choline chloride
Choline chloride
- Choline hydroxide
Choline hydroxide
- Synthesis
Synthesis | Choline
Template:Chembox new
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
# Overview
Choline is an organic compound, classified as an essential nutrient[1][2][3] and usually grouped within the Vitamin B complex. This natural amine is found in the lipids that make up cell membranes and in the neurotransmitter acetylcholine. Adequate intakes (AI) for this micronutrient of between 425 to 550 milligrams daily, for adults, have been established by the Food and Nutrition Board of the Institute of Medicine of the National Academy of Sciences.
# History
Choline was discovered by Andreas Strecker in 1864 and chemically synthesized in 1866. In 1998 choline was classified as an essential nutrient by the Food and Nutrition Board of the Institute of Medicine (U.S.A.).
# Chemistry
Choline is a quaternary saturated amine with the chemical formula: (CH3)3N+CH2CH2OHX−.
where X− is a counterion such as chloride (see choline chloride), hydroxide or tartrate.
# Physiology
Choline and its metabolites are needed for three main physiological purposes: structural integrity and signaling roles for cell membranes, cholinergic neurotransmission (acetylcholine synthesis), and as a major source for methyl groups via its metabolite, trimethylglycine (betaine) that participates in the S-adenosylmethionine synthesis pathways.
When choline is metabolized by the body, it may form trimethylamine, a compound with a fishy odor. Hence, when large amounts of choline are taken the person may suffer from a fishy body odor.
# Choline as a supplement
It is well established that supplements of methyl group transfer vitamins B6, B12, folic acid reduce the blood titer of homocysteine and prevent heart disease. Choline is a necessary source of methyl groups for methyl group transfer. Supplements of lecithin/choline by Central Soya scientists reduced heart disease in laboratory studies. The reduction in heart disease with lecithin supplements may however relate more to the cholesterol carrying capacity of lecithin than to the methyl group transfer role of choline.Template:Specify
Choline supplements are often taken as a form of 'smart drug' or nootropic, due to the the role that the neurotransmitter acetylcholine plays in various cognition systems within the brain. Choline is a chemical precursor or "building block" needed to produce the neurotransmitter acetylcholine, and research suggests that memory, intelligence and mood are mediated at least in part by acetylcholine metabolism in the brain. The efficacy, benefits and negative side effects of these supplements is a topic of continuing debate; research in the New England Journal of Medicine[citation needed] has suggested that choline supplements could have a detrimental effect on individuals who suffer from clinical depression or bipolar disorder, who seem to be hypersensitive to acetylcholine.
The Food and Drug Administration (FDA) requires that infant formula be made from cow's milk containing choline.[4]
Due to its role in lipid metabolism, choline has also found its way into nutritional supplements which claim to reduce body fat; but there is little or no evidence to prove that it has any effect on reducing excess body fat or that taking high amounts of choline will increase the rate at which fat is metabolised.
# Sources
The foods richest in phosphatidylcholine — the major delivery form of choline — are egg yolks, soy and cooked beef, chicken, veal and turkey livers. Many foods contain trace amounts of free choline, even iceberg lettuce. To what extent these trace forms are usable by human digestion is still debated. In 2004, the USDA released its first database of the choline content in common foods.[5]
The most often available choline dietary supplement is lecithin, derived from soy or egg yolks, often used as a food additive. Phosphatidylcholine is also available as a supplement, in pill or powder form. Supplementary Choline is also available as Choline Chloride, which comes as a liquid due to its hydrophilic properties. Choline chloride is sometimes preferred as a supplement because phosphatidylcholine can have gastrointestinal side effects.
# Additional images
- Choline chloride
Choline chloride
- Choline hydroxide
Choline hydroxide
- Synthesis
Synthesis | https://www.wikidoc.org/index.php/Arthropan | |
00aa517acacc22db85e82368046a03222585627e | wikidoc | Asphalt | Asphalt
Asphalt (Template:Audio-IPA) is a sticky, black and highly viscous liquid or semi-solid that is present in most crude petroleums and in some natural deposits sometimes termed asphaltum. It is most commonly modeled as a colloid, with asphaltenes as the dispersed phase and maltenes as the continuous phase (though there is some disagreement amongst chemists regarding its structure). In U.S. terminology, asphalt (or asphalt cement) is the carefully refined residue from the distillation process of selected crude oils. Outside North America, the product is called bitumen.
The primary use of asphalt (Bitumen) is in road construction, where it is used as the glue or binder for the aggregate particles. The road surfacing material is usually called 'asphalt concrete' in North America or simply 'asphalt' elsewhere. The apparent interchangeability of the words 'asphalt' and 'bitumen' causes confusion outside of the road construction industry despite quite clear definitions within industry circles.
# Background
Asphalt or bitumen can sometimes be confused with tar, which is a similar black thermo-plastic material produced by the destructive distillation of coal. During the early and mid twentieth century when town gas was produced, tar was a readily available product and extensively used as the binder for road aggregates. The addition of tar to macadam roads led to the word tarmac, which is now used in common parlance to refer to road making materials. However, since the 1970s, when natural gas succeeded town gas, asphalt (bitumen) has completely overtaken the use of tar in these applications.
Asphalt can be separated from the other components in crude oil (such as naphtha, gasoline and diesel) by the process of fractional distillation, usually under vacuum conditions. A better separation can be achieved by further processing of the heavier fractions of the crude oil in a de-asphalting unit, which uses either propane or butane in a supercritical phase to dissolve the lighter molecules which are then separated. Further processing is possible by "blowing" the product: namely reacting it with oxygen. This makes the product harder and more viscous.
Natural deposits of asphalt include lake asphalts (primarily from the Pitch Lake in Trinidad and Tobago and Bermudez Lake in Venezuela), Gilsonite, the Dead Sea between Israel & Jordan, and Tar Sands.
Asphalt is typically stored and transported at temperatures around 150 degrees Celsius (300 °F). Sometimes diesel oil or kerosene are mixed in before shipping to retain liquidity; upon delivery, these lighter materials are separated out of the mixture. This mixture is often called bitumen feedstock, or BFS. Some dump trucks route the hot engine exhaust through pipes in the dump body to keep the material warm. The backs of tippers carrying asphalt, as well as some handling equipment, are also commonly sprayed with a releasing agent before filling to aid release. Diesel oil is sometimes used as a release agent, although it can mix with and thereby reduce the quality of the asphalt.
# Known uses
## Ancient times
In the ancient Middle East, natural asphalt deposits were used for mortar between bricks and stones, ship caulking, and waterproofing. The Persian word for asphalt is mumiya, which may be related to the English word mummy. Asphalt was also used by ancient Egyptians to embalm mummies.
In the ancient Far East, natural asphalt was slowly boiled to get rid of the higher fractions, leaving a material of higher molecular weight which is thermoplastic and when layered on objects, became quite hard upon cooling. This was used to cover scabbards and other objects that needed water-proofing. Statuettes of household deities were also cast with this type of material in Japan, and probably also in China.Template:Facts
Poured bitumen has also been used as a damp-proof course in building.
## Rolled asphalt concrete
The largest use of asphalt is for making asphalt concrete for road surfaces and accounts for approximately 80% of the asphalt consumed in the United States. Roofing shingles account for most of the remaining asphalt consumption. Other uses include cattle sprays, fence post treatments, and waterproofing for fabrics.
Asphalt road surface is the most widely recycled material in the US, both by gross tonnage and by percentage. According to a report issued by the Federal Highway Administration and the United States Environmental Protection Agency, 80% of the asphalt from road surfaces' that is removed each year during widening and resurfacing projects is reused as part of new roads, roadbeds, shoulders and embankments.
## Mastic asphalt
Mastic asphalt is a type of asphalt which differs from dense graded asphalt (asphalt concrete) in that it has a higher bitumen (binder) content, usually around 7-10% of the whole aggregate mix, as opposed to roller asphalt, which has only around 5% added bitumen. Another asphalt which is fast gaining global popularity is stone mastic asphalt (SMA). SMA's advantages over rolled asphalt is its high anti skid qualities due to its high aggregate density and the lack of void content (air pockets). Another advantage of SMA is its longer durability over alternative road asphalt surfaces, but its manufacture and application, if not controlled closely, can result in slippery road surfaces due to excess bitumen pooling (bleeding) onto the surface.
## Asphalt emulsion
A number of technologies allow asphalt to be mixed at much lower temperatures. These involve mixing the asphalt with petroleum solvents to form "cutbacks" with reduced melting point or mixtures with water to turn the asphalt into an emulsion. Asphalt emulsions contain up to 70% asphalt and typically less than 1.5% chemical additives. There are two main types of emulsions with different affinity for aggregates, cationic and anionic. Asphalt emulsions are used in a wide variety of applications. Chipseal involves spraying the road surface with asphalt emulsion followed by a layer of crushed rock or gravel. Slurry Seal involves the creation of a mixture of asphalt emulsion and fine crushed aggregate that is spread on the surface of a road. Cold mixed asphalt can also be made from asphalt emulsion to create pavements similar to hot-mixed asphalt, several inches in depth and asphalt emulsions are also blended into recycled hot-mix asphalt to create low cost pavements.
## Mixing with petroleum-contaminated soil
Sometimes asphalt can be mixed with the output from low-temperature thermal desorption.
## Alternatives
The world has become increasingly concerned over the global climate change problem in recent years due to the pollution that is released into the atmosphere. Most of the emissions are derived primarily from burning fossil fuels. This has led to the introduction of bitumen alternatives that are more environmentally friendly and non toxic. Bitumen can now be made from non-petroleum based renewable resources such as sugar, molasses and rice, corn and potato starches etc. To further help the environment bitumen can also be made from the waste material vacuum tower bottoms produced in the process of cleaning used motor oils which helps the recycling industries, this waste is normally disposed by burning or dumping into land fills.
These new non-petroleum based bitumen binders can be colored, which thereby help reduce the temperatures of road surfaces which contribute to the Urban heat island which in turn contributes to global climate change.
For millions of people living in and around cities, heat islands are of growing concern. This phenomenon describes urban and suburban temperatures that are 2 to 10°F (1 to 6°C) hotter than nearby rural areas Elevated temperatures can impact communities by increasing peak energy demand, air conditioning costs, air pollution levels, and heat-related illness and mortality. Fortunately, there are common-sense measures that communities can take to reduce the negative effects of heat islands, such as replacing conventional black asphalt road surfaces with the new pigmentable bitumen that gives lighter colors .
Asphalt made with vegetable oil based binders was patented by Colas SA in France in 2004 (Vegecol), Colas was originally owned by the Royal Dutch Shell .
A number of homeowners seeking an environmentally-friendly alternative to asphalt for paving have experimented with waste vegetable oil as a binder for driveways and parking areas in single-family applications. The earliest known test occurred in 2002 in Ohio, where the homeowner combined waste vegetable oil with dry aggregate to create a low-cost and non-polluting paving material for his 200-foot driveway. After five years, he reports the driveway is performing as well or better than petroleum-based materials.
This movement has led the Shell Oil Company (see also, Controversies surrounding Royal Dutch Shell) to pave two public roads in Norway in 2007 with the Colas vegetable-oil-based asphalt.
Results of this study are still premature.
# Etymology
The word asphalt is derived from the late Middle English : from French asphalte, based on late Latin asphalton, asphaltum, from Greek asphalton, asphaltos (άσφαλτος), ásphaltos, -on, akin to asphalízein to make firm, to secure. | Asphalt
Template:Pp-semi-protected
Asphalt (Template:Audio-IPA) is a sticky, black and highly viscous liquid or semi-solid that is present in most crude petroleums and in some natural deposits sometimes termed asphaltum. It is most commonly modeled as a colloid, with asphaltenes as the dispersed phase and maltenes as the continuous phase (though there is some disagreement amongst chemists regarding its structure). In U.S. terminology, asphalt (or asphalt cement) is the carefully refined residue from the distillation process of selected crude oils. Outside North America, the product is called bitumen.
The primary use of asphalt (Bitumen) is in road construction, where it is used as the glue or binder for the aggregate particles. The road surfacing material is usually called 'asphalt concrete' in North America or simply 'asphalt' elsewhere. The apparent interchangeability of the words 'asphalt' and 'bitumen' causes confusion outside of the road construction industry despite quite clear definitions within industry circles.
# Background
Asphalt or bitumen can sometimes be confused with tar, which is a similar black thermo-plastic material produced by the destructive distillation of coal. During the early and mid twentieth century when town gas was produced, tar was a readily available product and extensively used as the binder for road aggregates. The addition of tar to macadam roads led to the word tarmac, which is now used in common parlance to refer to road making materials. However, since the 1970s, when natural gas succeeded town gas, asphalt (bitumen) has completely overtaken the use of tar in these applications.
Asphalt can be separated from the other components in crude oil (such as naphtha, gasoline and diesel) by the process of fractional distillation, usually under vacuum conditions. A better separation can be achieved by further processing of the heavier fractions of the crude oil in a de-asphalting unit, which uses either propane or butane in a supercritical phase to dissolve the lighter molecules which are then separated. Further processing is possible by "blowing" the product: namely reacting it with oxygen. This makes the product harder and more viscous.
Natural deposits of asphalt include lake asphalts (primarily from the Pitch Lake in Trinidad and Tobago and Bermudez Lake in Venezuela), Gilsonite, the Dead Sea between Israel & Jordan, and Tar Sands.
Asphalt is typically stored and transported at temperatures around 150 degrees Celsius (300 °F). Sometimes diesel oil or kerosene are mixed in before shipping to retain liquidity; upon delivery, these lighter materials are separated out of the mixture. This mixture is often called bitumen feedstock, or BFS. Some dump trucks route the hot engine exhaust through pipes in the dump body to keep the material warm. The backs of tippers carrying asphalt, as well as some handling equipment, are also commonly sprayed with a releasing agent before filling to aid release. Diesel oil is sometimes used as a release agent, although it can mix with and thereby reduce the quality of the asphalt.
# Known uses
## Ancient times
In the ancient Middle East, natural asphalt deposits were used for mortar between bricks and stones, ship caulking, and waterproofing. The Persian word for asphalt is mumiya, which may be related to the English word mummy. Asphalt was also used by ancient Egyptians to embalm mummies.
In the ancient Far East, natural asphalt was slowly boiled to get rid of the higher fractions, leaving a material of higher molecular weight which is thermoplastic and when layered on objects, became quite hard upon cooling. This was used to cover scabbards and other objects that needed water-proofing. Statuettes of household deities were also cast with this type of material in Japan, and probably also in China.Template:Facts
Poured bitumen has also been used as a damp-proof course in building.
## Rolled asphalt concrete
The largest use of asphalt is for making asphalt concrete for road surfaces and accounts for approximately 80% of the asphalt consumed in the United States. Roofing shingles account for most of the remaining asphalt consumption. Other uses include cattle sprays, fence post treatments, and waterproofing for fabrics.
Asphalt road surface is the most widely recycled material in the US, both by gross tonnage and by percentage. According to a report issued by the Federal Highway Administration and the United States Environmental Protection Agency, 80% of the asphalt from road surfaces' that is removed each year during widening and resurfacing projects is reused as part of new roads, roadbeds, shoulders and embankments.
## Mastic asphalt
Mastic asphalt is a type of asphalt which differs from dense graded asphalt (asphalt concrete) in that it has a higher bitumen (binder) content, usually around 7-10% of the whole aggregate mix, as opposed to roller asphalt, which has only around 5% added bitumen. Another asphalt which is fast gaining global popularity is stone mastic asphalt (SMA). SMA's advantages over rolled asphalt is its high anti skid qualities due to its high aggregate density and the lack of void content (air pockets). Another advantage of SMA is its longer durability over alternative road asphalt surfaces, but its manufacture and application, if not controlled closely, can result in slippery road surfaces due to excess bitumen pooling (bleeding) onto the surface.
## Asphalt emulsion
A number of technologies allow asphalt to be mixed at much lower temperatures. These involve mixing the asphalt with petroleum solvents to form "cutbacks" with reduced melting point or mixtures with water to turn the asphalt into an emulsion. Asphalt emulsions contain up to 70% asphalt and typically less than 1.5% chemical additives. There are two main types of emulsions with different affinity for aggregates, cationic and anionic. Asphalt emulsions are used in a wide variety of applications. Chipseal involves spraying the road surface with asphalt emulsion followed by a layer of crushed rock or gravel. Slurry Seal involves the creation of a mixture of asphalt emulsion and fine crushed aggregate that is spread on the surface of a road. Cold mixed asphalt can also be made from asphalt emulsion to create pavements similar to hot-mixed asphalt, several inches in depth and asphalt emulsions are also blended into recycled hot-mix asphalt to create low cost pavements.
## Mixing with petroleum-contaminated soil
Sometimes asphalt can be mixed with the output from low-temperature thermal desorption.
## Alternatives
The world has become increasingly concerned over the global climate change problem in recent years due to the pollution that is released into the atmosphere. Most of the emissions are derived primarily from burning fossil fuels. This has led to the introduction of bitumen alternatives that are more environmentally friendly and non toxic. Bitumen can now be made from non-petroleum based renewable resources such as sugar, molasses and rice, corn and potato starches etc. To further help the environment bitumen can also be made from the waste material vacuum tower bottoms produced in the process of cleaning used motor oils which helps the recycling industries, this waste is normally disposed by burning or dumping into land fills.
These new non-petroleum based bitumen binders can be colored, which thereby help reduce the temperatures of road surfaces which contribute to the Urban heat island which in turn contributes to global climate change.
For millions of people living in and around cities, heat islands are of growing concern. This phenomenon describes urban and suburban temperatures that are 2 to 10°F (1 to 6°C) hotter than nearby rural areas Elevated temperatures can impact communities by increasing peak energy demand, air conditioning costs, air pollution levels, and heat-related illness and mortality. Fortunately, there are common-sense measures that communities can take to reduce the negative effects of heat islands, such as replacing conventional black asphalt road surfaces with the new pigmentable bitumen that gives lighter colors [1] [2].
Asphalt made with vegetable oil based binders was patented by Colas SA in France in 2004 (Vegecol), Colas was originally owned by the Royal Dutch Shell [3]. [4]
A number of homeowners seeking an environmentally-friendly alternative to asphalt for paving have experimented with waste vegetable oil as a binder for driveways and parking areas in single-family applications. The earliest known test occurred in 2002 in Ohio, where the homeowner combined waste vegetable oil with dry aggregate to create a low-cost and non-polluting paving material for his 200-foot driveway. After five years, he reports the driveway is performing as well or better than petroleum-based materials.
This movement has led the Shell Oil Company (see also, Controversies surrounding Royal Dutch Shell) to pave two public roads in Norway in 2007 with the Colas vegetable-oil-based asphalt.
Results of this study are still premature.
# Etymology
The word asphalt is derived from the late Middle English : from French asphalte, based on late Latin asphalton, asphaltum, from Greek asphalton, asphaltos (άσφαλτος), ásphaltos, -on, akin to asphalízein to make firm, to secure. | https://www.wikidoc.org/index.php/Asphalt | |
1a31a097a2ad8b8ccf7a30029e6fa483e7659cff | wikidoc | Atavism | Atavism
An atavism is a real or supposed evolutionary throwback, such as traits reappearing which had disappeared generations ago. Atavisms occur because genes for previously existing phenotypical features are often preserved in DNA, even though the genes are not expressed in some or most of the organisms possessing them.
# Examples
Examples observed include:
- hind legs on whales
- hind fins on dolphins
- extra toes on horses, as in archaic horses
- reemergence of sexual reproduction in Hieracium pilosella and Crotoniidae
Atavisms have been observed in humans as well. For example, babies have been born with a vestigial tail, called "coccygeal process", "coccygeal projection", and "caudal appendage". It can also be evidenced in humans who possess large, ape-like teeth.
# Atavism in history
During the interval between the acceptance of evolution and the rise of modern understanding of genetics, atavism was used to account for the reappearance in an individual of a trait after several generations of absence. Such an individual was sometimes called a "throwback". The term is often used in connection with the unexpected reappearance of primitive traits in organisms.
The notion of atavism was used frequently by social Darwinists, who claimed that inferior races displayed atavistic traits, and represented more primitive traits than their own race. Both the notion of atavism, and Haeckel's recapitulation theory, are saturated with notions of evolution as progress, as a march towards greater complexity and superior ability.
In addition, the concept of atavism as part of an individualistic explanation of the causes of criminal deviance was popularised by the Italian criminologist Cesare Lombroso in the 1870s. He attempted to identify physical characteristics common to criminals and labeled those he found as atavistic, ‘throwback’ traits that determined 'primitive' criminal behavior. His statistical evidence and the notion that physical traits determine inevitable criminality (an idea closely related to the concepts of eugenics) have long since been debunked, but the concept that physical traits may affect the likelihood of criminal behavior in the individual remains popular in some circles.
The notion that somehow, atavisms could be made to accumulate by selective breeding led to breeds such as the Heck cattle. This had been bred from ancient landraces with selected primitive traits, in an attempt of "reviving" the extinct aurochs.
# Cultural references to atavism
The term atavism is sometimes also applied in the discussion of culture. Some social scientists describe the return of older, "more primitive" tendencies (e.g., warlike attitudes, "clan identity," etc. -- anything suggesting the social and political atmosphere of thousands of years ago) as "atavistic." "Resurgent Atavism" is a common name for the belief that people in the modern era are beginning to revert to ways of thinking and acting that are throwbacks to a former time. This is especially used by sociologists in reference to violence. Marxists refer to pre-capitalist classes (such as the peasantry, the aristocracy and the petit-bourgeoisie) as "atavistic" to indicate that they do not fit into the bipolar class division (bourgeoisie/proletariat) of modern capitalist society. Marxists therefore view them as a reactionary force that will try to stop not only socialism, but also bourgeois progress itself.
The neo-pagan subculture also uses this same terminology ("atavism" or "resurgent atavism") to describe how modern, Western countries are experiencing both the decline of Christianity and the rise of religious movements inspired by the pagan religions of centuries past. Some cite the rise of environmentalism, scientific inquiry, and liberalization of society as contributing to an increasingly secular society, one in which religious sentiments are more frequently tied with an appreciation of the physical world rather than set against it. Occasionally, the use of these terms in reference to "alternative" spirituality or in an occult context implies the use of violence to assert these changing religious views--for example, in the book Lords of Chaos a rash of church burnings across Scandinavia has been described as a part of this trend because many of the perpetrators were self-described "pagans" seeking to overthrow what they deemed to be centuries of religious oppression by Christianity.
Atavism is a key term in Joseph Schumpeter's explanation of World War I in 20th Century liberal Europe. He defends the liberal belief in international relations that an international society built on commerce will avoid war because of its destructiveness and comparative cost. His reason for WWI is termed "Atavism," in which he claims the vestigial governments in Europe (the German Empire, Russian Empire, Ottoman Empire, and Austro-Hungarian Empire) pulled the liberal Europe into war, and that the liberal structure of the continent did not cause it. He uses this idea to say that liberalism and commerce will continue to have a soothing effect in international relations, and that war will not arise in nations who are built on commercial ties. | Atavism
An atavism is a real or supposed evolutionary throwback, such as traits reappearing which had disappeared generations ago.[1] Atavisms occur because genes for previously existing phenotypical features are often preserved in DNA, even though the genes are not expressed in some or most of the organisms possessing them.
# Examples
Examples observed include:
- hind legs on whales[1]
- hind fins on dolphins[1][2]
- extra toes on horses, as in archaic horses
- reemergence of sexual reproduction in Hieracium pilosella and Crotoniidae[3]
Atavisms have been observed in humans as well. For example, babies have been born with a vestigial tail, called "coccygeal process", "coccygeal projection", and "caudal appendage".[1] It can also be evidenced in humans who possess large, ape-like teeth.[4]
# Atavism in history
During the interval between the acceptance of evolution and the rise of modern understanding of genetics, atavism was used to account for the reappearance in an individual of a trait after several generations of absence. Such an individual was sometimes called a "throwback". The term is often used in connection with the unexpected reappearance of primitive traits in organisms.
The notion of atavism was used frequently by social Darwinists, who claimed that inferior races displayed atavistic traits, and represented more primitive traits than their own race. Both the notion of atavism, and Haeckel's recapitulation theory, are saturated with notions of evolution as progress, as a march towards greater complexity and superior ability.
In addition, the concept of atavism as part of an individualistic explanation of the causes of criminal deviance was popularised by the Italian criminologist Cesare Lombroso in the 1870s. He attempted to identify physical characteristics common to criminals and labeled those he found as atavistic, ‘throwback’ traits that determined 'primitive' criminal behavior. His statistical evidence and the notion that physical traits determine inevitable criminality (an idea closely related to the concepts of eugenics) have long since been debunked, but the concept that physical traits may affect the likelihood of criminal behavior in the individual remains popular in some circles.
The notion that somehow, atavisms could be made to accumulate by selective breeding led to breeds such as the Heck cattle. This had been bred from ancient landraces with selected primitive traits, in an attempt of "reviving" the extinct aurochs.
# Cultural references to atavism
The term atavism is sometimes also applied in the discussion of culture. Some social scientists describe the return of older, "more primitive" tendencies (e.g., warlike attitudes, "clan identity," etc. -- anything suggesting the social and political atmosphere of thousands of years ago) as "atavistic." "Resurgent Atavism" is a common name for the belief that people in the modern era are beginning to revert to ways of thinking and acting that are throwbacks to a former time. This is especially used by sociologists in reference to violence. Marxists refer to pre-capitalist classes (such as the peasantry, the aristocracy and the petit-bourgeoisie) as "atavistic" to indicate that they do not fit into the bipolar class division (bourgeoisie/proletariat) of modern capitalist society. Marxists therefore view them as a reactionary force that will try to stop not only socialism, but also bourgeois progress itself.
The neo-pagan subculture also uses this same terminology ("atavism" or "resurgent atavism") to describe how modern, Western countries are experiencing both the decline of Christianity and the rise of religious movements inspired by the pagan religions of centuries past. Some cite the rise of environmentalism, scientific inquiry, and liberalization of society as contributing to an increasingly secular society, one in which religious sentiments are more frequently tied with an appreciation of the physical world rather than set against it.[citation needed] Occasionally, the use of these terms in reference to "alternative" spirituality or in an occult context implies the use of violence to assert these changing religious views--for example, in the book Lords of Chaos a rash of church burnings across Scandinavia has been described as a part of this trend because many of the perpetrators were self-described "pagans" seeking to overthrow what they deemed to be centuries of religious oppression by Christianity.
Atavism is a key term in Joseph Schumpeter's explanation of World War I in 20th Century liberal Europe. He defends the liberal belief in international relations that an international society built on commerce will avoid war because of its destructiveness and comparative cost. His reason for WWI is termed "Atavism," in which he claims the vestigial governments in Europe (the German Empire, Russian Empire, Ottoman Empire, and Austro-Hungarian Empire) pulled the liberal Europe into war, and that the liberal structure of the continent did not cause it. He uses this idea to say that liberalism and commerce will continue to have a soothing effect in international relations, and that war will not arise in nations who are built on commercial ties. | https://www.wikidoc.org/index.php/Atavism | |
0140a6b06c574aae59026f519a482df54db68904 | wikidoc | Dieting | Dieting
# Overview
Dieting is the practice of ingesting food in a regulated fashion to achieve a particular objective. In many cases the goal is weight loss, but some athletes aspire to gain weight (usually in the form of muscle) and diets can also be used to maintain a stable body weight.
# Historical Perspective
In the broadest sense, at least some targeted dieting has clearly existed since prehistoric times for various social, religious, and biological reasons.
See Luigi Cornaro for a 16th century treatise on dieting. Throughout the 17th and 18th centuries, physicians and patients regulated their food carefully, in order to prevent disease. In the 19th century, as the scientific classification of foods took shape, doctors and scientists began experimenting with targeted diets.
William Banting is one of the first people known to have successfully lost weight by developing a targeted diet, circa 1863, by targeting carbohydrates. The low carbohydrate diet, sometimes marketed today as the Atkins Diet, remains popular today.
# Classification
There are several kinds of diets:
- Weight-loss diets restrict the intake of specific foods, or food in general, to reduce body weight. What works to reduce body weight for one person will not necessarily work for another, due to metabolic differences and lifestyle factors. Also, for a variety of reasons, most people find it very difficult to maintain significant weight loss over time. There is some thought that losing weight quickly may actually make it more difficult to maintain the loss over time. It is also possible that cutting calorie intake too low slows or prevents weight loss. The National Institutes of Health notes that the commonly recommended program of reduced caloric intake along with increased physical activity has a long-term failure rate of 98%.
- Many professional athletes impose weight-gain diets on themselves. American football players may try to "bulk up" through weight-gain diets in order to gain an advantage on the field with a higher mass.
- Individuals who are underweight, such as those recovering from anorexia nervosa or from starvation, may undergo weight-gain diets which, unlike those of athletes, has the goal of restoring normal levels of body fat, muscle, and stores of essential nutrients.
Many people in the acting industry may choose to lose or gain weight depending on the role they're given.
# Physiology
## In Children and Young Adults
Receiving adequate nutrition through a well-balanced diet is critical during childhood and adolescence. Unless a doctor says otherwise, low-carb, low-fat, or other specialty diets for children who are not heavily obese are unhealthy because they deprive the body of the building blocks of cells (namely energy and lipids in the above examples).
It is especially notable that, as more cultures scrutinize their diets, many improperly educated mothers consider putting their children on restricted diets that actually do more harm than good. This is extremely deleterious to a young child's health because a full and balanced diet (fats, carbohydrates, protein, vitamins, minerals, fiber, etc.) is needed for growth. Vegetarian diets can work for children as long as all needed nutrients are received. A doctor should be consulted before putting any child on a specialized diet.
Research also shows that putting children on diet foods can be harmful. The brain is unable to learn how to correlate taste with nutritional value, which is why such children may consistently overeat later in life despite adequate nutritional intake.
## Thermoregulation
According to the principles of thermoregulation, humans are endotherms. We expend energy to maintain our blood temperature at body temperature, which is about 37 °C (98.6 °F). This is accomplished by metabolism and blood circulation, by shivering to stay warm, and by sweating to stay cool.
In addition to thermoregulation, humans expend energy keeping the vital organs (especially the lungs, heart and brain) functioning. Except when sleeping, our skeletal muscles are working, typically to maintain upright posture. The average work done just to stay alive is the basal metabolic rate, which (for humans) is about 1 watt per kilogram (2.2 lbs) of body mass. Thus, an average man of 75 kilograms (165 lbs) who just rests (or only walks a few steps) burns about 75 watts (continuously), or about 6,500 kilojoules (1,440 Calories) per day or 1 Calorie each minute.
## Physical Exercise
Physical exercise is an important complement to dieting in securing weight loss. Aerobic exercise is also an important part of maintaining normal good health, especially the muscular strength of the heart. To be useful, aerobic exercise requires maintaining a target heart rate of above 50 percent of one's resting heart rate for 30 minutes, at least 3 times a week. Brisk walking can accomplish this.
The ability of a few hours a week of exercise to contribute to weight loss can be somewhat overestimated. To illustrate, consider a 100-kilogram (220 lbs) man who wants to lose 10 kilograms (22 lbs) and assume that he eats just enough to maintain his weight (at rest), so that weight loss can only come from exercise. Those 10 (22 lbs) kilograms converted to work are equivalent to about 350 megajoules. (We use an approximation of the standard 37 kilojoules or 9 Calories per gram of fat.) Now assume that his chosen exercise is stairclimbing and that he is 20 percent efficient at converting chemical energy into mechanical work (this is within measured ranges). To lose the weight, he must ascend 70 kilometers. A man of normal fitness (like him) will be tired after 500 meters of climbing (about 150 flights of stairs), so he needs to exercise every day for 140 days (to reach his target). However, exercise (both aerobic and anaerobic) would increase the Basal Metabolic Rate (BMR) for some time after the workout. This ensures more calorific loss than otherwise estimated.
The minimum safe dietary energy intake (without medical supervision) is 75 percent of that needed to maintain basal metabolism. For our hypothetical 100-kilogram man, that minimum is about 5,700 kilojoules (1,300 calories) per day. By combining daily aerobic exercise with a weight-loss diet, he would be able to lose 10 kilograms in half the time (70 days). Of course, the described regime is more rigorous than would be desirable or advisable for many persons. Therefore, under an effective but more manageable weight-loss program, losing 10 kilograms (about 20 pounds) may take as long as 6 months.
There are also some easy ways for people to exercise, such as walking rather than driving, climbing stairs instead of taking elevators, doing more housework with fewer power tools, or parking their cars farther and walking to school or the office.
## Fat Loss versus Muscle Loss
It is important to understand the difference between weight loss and fat loss. Weight loss typically involves the loss of fat, water and muscle. A dieter can lose weight without losing much fat. Ideally, overweight people should seek to lose fat and preserve muscle, since muscle burns more calories than fat. Generally, the more muscle mass one has, the higher one's metabolism is, resulting in more calories being burned, even at rest. Since muscles are more dense than fat, muscle loss results in little loss of physical bulk compared with fat loss. To determine whether weight loss is due to fat, various methods of measuring body fat percentage have been developed.
Muscle loss during weight loss can be restricted by regularly lifting weights (or doing push-ups and other strength-oriented calisthenics) and by maintaining sufficient protein intake. According to the National Academy of Sciences, the Dietary Reference Intake for protein is "0.8 grams per kilogram of body weight for adults."
Those on low-carbohydrate diets, and those doing particularly strenuous exercise, may wish to increase their protein intake which is necessary. However, there may be risks involved. According to the American Heart Association, excessive protein intake may cause liver and kidney problems and may be a risk factor for heart disease. There is no conclusive evidence that moderately high protein diets in healthy individuals are dangerous, however, it has only been shown that these diets are dangerous in individuals who already have kidney and liver problems.
## How the body gets rid of Fat
All body processes require energy to run properly. When the body is expending more energy than it is taking in (e.g. when exercising), body cells rely on internally stored energy sources, like complex carbohydrates and fats, for energy. The first source the body turns to is glycogen, which is a complex carbohydrate created by the body. When that source is nearly depleted, the body begins lipolysis, the metabolism of fat for energy. In this process, fats, obtained from fat cells, are broken down into glycerol and fatty acids, which can be used to make energy. The primary by-products of metabolism are carbon dioxide and water; carbon dioxide is expelled through the respiratory system.
Fats are also secreted by the sebaceous glands (in the skin).
# Nutrition
## Energy obtained from Food
The energy humans get from food is limited by the efficiency of digestion and the efficiency of utilization. The efficiency of digestion is largely dependent on the type of food being eaten. Poorly chewed seeds are poorly digested. Refined sugars and fats are absorbed almost completely. Chewing does not compensate for the calorie content of a food that is eaten; even celery, which is primarily indigestible cellulose, contains enough sugars to easily compensate for the cost of chewing it.
## Proper Nutrition
Food provides nutrients from six broad classes: proteins, fats, carbohydrates, vitamins, dietary minerals, and water. Carbohydrates are metabolized to provide energy. Proteins provide amino acids, which are required for cell, especially muscle, construction. Essential fatty acids are required for brain and cell membrane construction. Vitamins and trace minerals help maintain proper electrolyte balance and are required for many metabolic processes.
Any diet that fails to meet minimum nutritional requirements can threaten general health (and physical fitness in particular). If a person is not well enough to be active, weight loss and good quality of life will be unlikely.
The National Academy of Sciences and the World Health Organization publish guidelines for dietary intakes of all known essential nutrients.
Sometimes dieters will ingest excessive amounts of vitamin and mineral supplements. While this is usually harmless, some nutrients are dangerous. Men (and women who don't menstruate) need to be wary of iron poisoning. Retinol (oil-soluble vitamin A) is toxic in large doses. As a general rule, most people can get the nutrition they need from foods (there are specific exceptions; vegans often need to supplement vitamin B12). In any event, a multivitamin taken once a day will suffice for the majority of the population.
A sensible weight-loss diet is a normal balanced diet; it just comes with smaller portions and perhaps some substitutions (e.g. low-fat milk, or less salad dressing). Extreme diets may lead to malnutrition, and are less likely to be effective at long-term weight loss in any event.
# Dieting
## Psychological Aspects of Weight-Loss Dieting
Diets affect the energy in component of the energy balance by limiting or altering the distribution of foods. Techniques that affect the appetite can limit energy intake by affecting the desire to overeat.
Consumption of low-energy, fiber-rich foods, such as non-starchy vegetables, is effective in obtaining satiation (the feeling of "fullness"). Exercise is also useful in controlling appetite as is drinking water and sleeping. (Extreme physical fatigue, such as experienced by soldiers and mountain climbers, can make eating a difficult chore.)
The use of drugs to control appetite is also common. Stimulants are often taken as a means to suppress (normal, healthy) hunger by people who are dieting. Ephedrine (through facilitating the release of adrenaline and noradrenaline) stimulates the alpha(1)-adrenoreceptor subtype, which is known to act as an anorectic. L-Phenylalanine, an amino acid found in whey protein powders also has the ability to suppress appetite by increasing the hormone cholecystokinin (CCK) which sends a satiety signal to the brain.
## Weight Loss Groups
There exist both profit-oriented and non-profit weight loss organizations who assist people in their weight loss efforts. An example of the former is Weight Watchers ; examples of the latter include Overeaters Anonymous, as well as a multitude of non-branded support groups run by local churches, hospitals, and like-minded individuals.
These organizations' customs and practices differ widely. Some groups are modeled on twelve-step programs, while others are quite informal. Some groups advocate certain prepared foods or special menus, while others train dieters to make healthy choices from restaurant menus and while grocery-shopping and cooking.
Most groups leverage the power of group meetings to provide counseling, emotional support, problem-solving, and useful information.
## Low-Fat Diets
In a meta-analysis of 11 randomized controlled trials that compared low fat versus low carbohydrate diets, low fat diets achieved greater reduction in low density lipoprotein but less weight loss and less increase in high density lipoprotein. A more recent cohort study comparing low fat versus low carbohydrate diets for mortality concluded "overall low-carbohydrate-diet and low-fat-diet scores were not associated with total mortality. Unhealthy low-carbohydrate-diet and low-fat-diet scores were associated with higher total mortality, whereas healthy low-carbohydrate-diet and low-fat-diet scores were associated with lower total mortality".
The proportion of dietary fat that is unsaturated fat with cis-trans isomerism such as omega-3 fatty acid and monounsaturated fats may be more important than the amount of dietary fat.
## Atkins Diet (low carbohydrate)
The Atkins diet was developed by Dr. Robert Atkins' and intended to control blood sugar by reducing the number of carbohydrates consumed (particularly refined carbohydrates) while replacing them with significant quantities of fat and protein. The Atkins diet was originally designed for diabetes patients who wanted to manage their insulin levels more effectively. The short-term changes experienced by individuals on the Atkins diet include some rapid weight-loss as the body's glycogen stores were depleted, reducing fasting levels of triglycerides and an increasing blood-bound ketones. The diet also causes acidosis and mild fatigue.
## Mediterranean Diet
The Mediterranean diet emphasizes monounsaturated fats and may reduce cardiovascular disease.
## Natural Diets
Since the advent of controversial diets such as Atkins, various diets that stress the eating habits of "natural humans" have been developed. The Paleolithic Diet imitates the way people ate during the Stone Age. These eating plans include basically natural foods (those not processed by humans). Whereas the Paleolithic Diet excludes milk and grain-foods, The Evolution Diet excludes human-made ingredients such as partially hydrogenated oils but allows some processed foods such as whole-grain crackers and dairy products. Anthropologists who focus their research on human evolution, however, are quick to point out that the diet of Paleolithic peoples was most likely opportunistic. That is, these early humans would most likely eat whatever edible foods were available at any given moment in that particular area (e.g. vegetables, termites, meat) and not restrict their intake of any food. Until recent human history, starvation has been a far greater threat than over-consumption.
## Time-Restricted Eating
Time-Restricted Eating may not be effective at weight loss.
## Vegetarian diet
There is a growing body of evidence that vegetarian diets can prevent obesity and lower disease risks.
According to the American Dietetic Association, "Vegetarians have been reported to have lower body mass indices than nonvegetarians, as well as lower rates of death from ischemic heart disease; vegetarians also show lower blood cholesterol levels; lower blood pressure; and lower rates of hypertension, type 2 diabetes, and prostate and colon cancer."
Vegetarians on average weigh 10 percent less than non-vegetarians. And in a year-long study comparing Dean Ornish's vegetarian diet to Weight Watchers, The Zone Diet, and The Atkins Diet, subjects on The Atkins Diet achieved the most weight loss (on average). Strict vegetarian diets like veganism may result in certain vitamin and mineral deficiencies if attention isn't paid to nutrition.
## Weight Watchers
Weight Watchers has two programs. The program offers a wide variety and foods. Each food has a point value. They encourage a well rounded diet, low in fat and high in fruits and vegetables. The core plan focuses more on portion control and natural foods. According to Weight Watchers, the act of keeping track of what one eats is very helpful in reducing overeating or eating for reasons other than hunger.
# Dangers of Dieting
Extreme calorie restriction, medication or unusual patterns of eating (i.e. restricting food consumption to a single fruit or meal) can be dangerous.
## ACC/AHA/ESC 2006 Guidelines for Management of Patients With Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death - Obesity, Dieting, and Anorexia (DO NOT EDIT)
## Medications
Certain medications can be prescribed to assist in weight loss. Some, like amphetamines, are dangerous now banned for casual weight loss. Others, including those containing vitamins and minerals, are not effective for losing weight.
### Diuretics
Diuretics induce weight loss through the excretion of water. These medication or herbs will reduce the amount that a body weighs, but will have no effect on an individual's body fat. Diuretics can thicken the blood, cause cramping, kidney and liver damage.
### Stimulants
Stimulants such as ephedrine (now illegal in the United States due to an FDA ban) or synephrine work to increase the basal metabolic rate and reduce appetite. Stimulants can cause kidney and liver damage, sudden heart attacks, addiction, and ischemic strokes.
In June 2006, the European Union approved the sale of the diet drug rimonabant, marketed under the trade name Acomplia. This new class of diet pills shows some promise in assisting physician-prescribed diets.
## Dangers of Fasting
Lengthy fasting can be dangerous due to the risk of malnutrition and should be carried out under medical supervision. During fasting, low-carbohydrate or very low calorie diets a lack of blood glucose, the preferred energy source of the brain, causes the body to metabolize sugars from protein, which can lead to muscle wasting.
## Side effects
Dieting, especially extreme food-intake reduction and rapid weight loss, can have the following side effects:
- Prolonged hunger
- Depression
- Reduced sex drive
- Fatigue
- Irritability
- Fainting
- Sinus problems (especially post-nasal drip)
- Muscle atrophy
- Rashes
- Acidosis
- Bloodshot eyes
- Gallbladder disease
- Seizures
- Weight gain on discontinuation
- Malnutrition, possibly leading to death
# Related Chapters
- Body image
- Crash diet
- Diet aid
- Dietitian
- Food faddism
- Healthy diet
- List of diets
- National Weight Control Registry
- Nutritional rating systems
- Nutrition scale
- Underweight | Dieting
}
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
# Overview
Dieting is the practice of ingesting food in a regulated fashion to achieve a particular objective. In many cases the goal is weight loss, but some athletes aspire to gain weight (usually in the form of muscle) and diets can also be used to maintain a stable body weight.
# Historical Perspective
In the broadest sense, at least some targeted dieting has clearly existed since prehistoric times for various social, religious, and biological reasons.
See Luigi Cornaro for a 16th century treatise on dieting. Throughout the 17th and 18th centuries, physicians and patients regulated their food carefully, in order to prevent disease. In the 19th century, as the scientific classification of foods took shape, doctors and scientists began experimenting with targeted diets.
William Banting is one of the first people known to have successfully lost weight by developing a targeted diet, circa 1863, by targeting carbohydrates. The low carbohydrate diet, sometimes marketed today as the Atkins Diet, remains popular today.
# Classification
There are several kinds of diets:
- Weight-loss diets restrict the intake of specific foods, or food in general, to reduce body weight. What works to reduce body weight for one person will not necessarily work for another, due to metabolic differences and lifestyle factors. Also, for a variety of reasons, most people find it very difficult to maintain significant weight loss over time. There is some thought that losing weight quickly may actually make it more difficult to maintain the loss over time. It is also possible that cutting calorie intake too low slows or prevents weight loss. The National Institutes of Health notes that the commonly recommended program of reduced caloric intake along with increased physical activity has a long-term failure rate of 98%.
- Many professional athletes impose weight-gain diets on themselves. American football players may try to "bulk up" through weight-gain diets in order to gain an advantage on the field with a higher mass.
- Individuals who are underweight, such as those recovering from anorexia nervosa or from starvation, may undergo weight-gain diets which, unlike those of athletes, has the goal of restoring normal levels of body fat, muscle, and stores of essential nutrients.
Many people in the acting industry may choose to lose or gain weight depending on the role they're given.
# Physiology
## In Children and Young Adults
Receiving adequate nutrition through a well-balanced diet is critical during childhood and adolescence. Unless a doctor says otherwise, low-carb, low-fat, or other specialty diets for children who are not heavily obese are unhealthy because they deprive the body of the building blocks of cells (namely energy and lipids in the above examples).
It is especially notable that, as more cultures scrutinize their diets, many improperly educated mothers consider putting their children on restricted diets that actually do more harm than good. This is extremely deleterious to a young child's health because a full and balanced diet (fats, carbohydrates, protein, vitamins, minerals, fiber, etc.) is needed for growth. Vegetarian diets can work for children as long as all needed nutrients are received. A doctor should be consulted before putting any child on a specialized diet.
Research also shows that putting children on diet foods can be harmful. The brain is unable to learn how to correlate taste with nutritional value, which is why such children may consistently overeat later in life despite adequate nutritional intake. [1]
## Thermoregulation
According to the principles of thermoregulation, humans are endotherms. We expend energy to maintain our blood temperature at body temperature, which is about 37 °C (98.6 °F). This is accomplished by metabolism and blood circulation, by shivering to stay warm, and by sweating to stay cool.[2]
In addition to thermoregulation, humans expend energy keeping the vital organs (especially the lungs, heart and brain) functioning. Except when sleeping, our skeletal muscles are working, typically to maintain upright posture. The average work done just to stay alive is the basal metabolic rate, which (for humans) is about 1 watt per kilogram (2.2 lbs) of body mass. Thus, an average man of 75 kilograms (165 lbs) who just rests (or only walks a few steps) burns about 75 watts (continuously), or about 6,500 kilojoules (1,440 Calories) per day or 1 Calorie each minute.
## Physical Exercise
Physical exercise is an important complement to dieting in securing weight loss. Aerobic exercise is also an important part of maintaining normal good health, especially the muscular strength of the heart. To be useful, aerobic exercise requires maintaining a target heart rate of above 50 percent of one's resting heart rate for 30 minutes, at least 3 times a week. Brisk walking can accomplish this.
The ability of a few hours a week of exercise to contribute to weight loss can be somewhat overestimated. To illustrate, consider a 100-kilogram (220 lbs) man who wants to lose 10 kilograms (22 lbs) and assume that he eats just enough to maintain his weight (at rest), so that weight loss can only come from exercise. Those 10 (22 lbs) kilograms converted to work are equivalent to about 350 megajoules. (We use an approximation of the standard 37 kilojoules or 9 Calories per gram of fat.) Now assume that his chosen exercise is stairclimbing and that he is 20 percent efficient at converting chemical energy into mechanical work (this is within measured ranges). To lose the weight, he must ascend 70 kilometers. A man of normal fitness (like him) will be tired after 500 meters of climbing (about 150 flights of stairs), so he needs to exercise every day for 140 days (to reach his target). However, exercise (both aerobic and anaerobic) would increase the Basal Metabolic Rate (BMR) for some time after the workout. This ensures more calorific loss than otherwise estimated.
The minimum safe dietary energy intake (without medical supervision) is 75 percent of that needed to maintain basal metabolism. For our hypothetical 100-kilogram man, that minimum is about 5,700 kilojoules (1,300 calories) per day. By combining daily aerobic exercise with a weight-loss diet, he would be able to lose 10 kilograms in half the time (70 days). Of course, the described regime is more rigorous than would be desirable or advisable for many persons. Therefore, under an effective but more manageable weight-loss program, losing 10 kilograms (about 20 pounds) may take as long as 6 months.
There are also some easy ways for people to exercise, such as walking rather than driving, climbing stairs instead of taking elevators, doing more housework with fewer power tools, or parking their cars farther and walking to school or the office.
## Fat Loss versus Muscle Loss
It is important to understand the difference between weight loss and fat loss. Weight loss typically involves the loss of fat, water and muscle. A dieter can lose weight without losing much fat. Ideally, overweight people should seek to lose fat and preserve muscle, since muscle burns more calories than fat. Generally, the more muscle mass one has, the higher one's metabolism is, resulting in more calories being burned, even at rest. Since muscles are more dense than fat, muscle loss results in little loss of physical bulk compared with fat loss. To determine whether weight loss is due to fat, various methods of measuring body fat percentage have been developed.
Muscle loss during weight loss can be restricted by regularly lifting weights (or doing push-ups and other strength-oriented calisthenics) and by maintaining sufficient protein intake. According to the National Academy of Sciences, the Dietary Reference Intake for protein is "0.8 grams per kilogram of body weight for adults."
Those on low-carbohydrate diets, and those doing particularly strenuous exercise, may wish to increase their protein intake which is necessary. However, there may be risks involved. According to the American Heart Association, excessive protein intake may cause liver and kidney problems and may be a risk factor for heart disease.[3] There is no conclusive evidence that moderately high protein diets in healthy individuals are dangerous, however, it has only been shown that these diets are dangerous in individuals who already have kidney and liver problems.
## How the body gets rid of Fat
All body processes require energy to run properly. When the body is expending more energy than it is taking in (e.g. when exercising), body cells rely on internally stored energy sources, like complex carbohydrates and fats, for energy. The first source the body turns to is glycogen, which is a complex carbohydrate created by the body. When that source is nearly depleted, the body begins lipolysis, the metabolism of fat for energy. In this process, fats, obtained from fat cells, are broken down into glycerol and fatty acids, which can be used to make energy. The primary by-products of metabolism are carbon dioxide and water; carbon dioxide is expelled through the respiratory system.
Fats are also secreted by the sebaceous glands (in the skin).
# Nutrition
## Energy obtained from Food
The energy humans get from food is limited by the efficiency of digestion and the efficiency of utilization. The efficiency of digestion is largely dependent on the type of food being eaten. Poorly chewed seeds are poorly digested. Refined sugars and fats are absorbed almost completely. Chewing does not compensate for the calorie content of a food that is eaten; even celery, which is primarily indigestible cellulose, contains enough sugars to easily compensate for the cost of chewing it.
## Proper Nutrition
Food provides nutrients from six broad classes: proteins, fats, carbohydrates, vitamins, dietary minerals, and water. Carbohydrates are metabolized to provide energy. Proteins provide amino acids, which are required for cell, especially muscle, construction. Essential fatty acids are required for brain and cell membrane construction. Vitamins and trace minerals help maintain proper electrolyte balance and are required for many metabolic processes.
Any diet that fails to meet minimum nutritional requirements can threaten general health (and physical fitness in particular). If a person is not well enough to be active, weight loss and good quality of life will be unlikely.
The National Academy of Sciences and the World Health Organization publish guidelines for dietary intakes of all known essential nutrients.
Sometimes dieters will ingest excessive amounts of vitamin and mineral supplements. While this is usually harmless, some nutrients are dangerous. Men (and women who don't menstruate) need to be wary of iron poisoning. Retinol (oil-soluble vitamin A) is toxic in large doses. As a general rule, most people can get the nutrition they need from foods (there are specific exceptions; vegans often need to supplement vitamin B12). In any event, a multivitamin taken once a day will suffice for the majority of the population.
A sensible weight-loss diet is a normal balanced diet; it just comes with smaller portions and perhaps some substitutions (e.g. low-fat milk, or less salad dressing). Extreme diets may lead to malnutrition, and are less likely to be effective at long-term weight loss in any event.
# Dieting
## Psychological Aspects of Weight-Loss Dieting
Diets affect the energy in component of the energy balance by limiting or altering the distribution of foods. Techniques that affect the appetite can limit energy intake by affecting the desire to overeat.
Consumption of low-energy, fiber-rich foods, such as non-starchy vegetables, is effective in obtaining satiation (the feeling of "fullness"). Exercise is also useful in controlling appetite as is drinking water and sleeping. (Extreme physical fatigue, such as experienced by soldiers and mountain climbers, can make eating a difficult chore.)
The use of drugs to control appetite is also common. Stimulants are often taken as a means to suppress (normal, healthy) hunger by people who are dieting. Ephedrine (through facilitating the release of adrenaline and noradrenaline) stimulates the alpha(1)-adrenoreceptor subtype, which is known to act as an anorectic. L-Phenylalanine, an amino acid found in whey protein powders also has the ability to suppress appetite by increasing the hormone cholecystokinin (CCK) which sends a satiety signal to the brain.
## Weight Loss Groups
There exist both profit-oriented and non-profit weight loss organizations who assist people in their weight loss efforts. An example of the former is Weight Watchers ; examples of the latter include Overeaters Anonymous, as well as a multitude of non-branded support groups run by local churches, hospitals, and like-minded individuals.
These organizations' customs and practices differ widely. Some groups are modeled on twelve-step programs, while others are quite informal. Some groups advocate certain prepared foods or special menus, while others train dieters to make healthy choices from restaurant menus and while grocery-shopping and cooking.
Most groups leverage the power of group meetings to provide counseling, emotional support, problem-solving, and useful information.
## Low-Fat Diets
In a meta-analysis of 11 randomized controlled trials that compared low fat versus low carbohydrate diets, low fat diets achieved greater reduction in low density lipoprotein but less weight loss and less increase in high density lipoprotein.[4] A more recent cohort study comparing low fat versus low carbohydrate diets for mortality concluded "overall low-carbohydrate-diet and low-fat-diet scores were not associated with total mortality. Unhealthy low-carbohydrate-diet and low-fat-diet scores were associated with higher total mortality, whereas healthy low-carbohydrate-diet and low-fat-diet scores were associated with lower total mortality"[5].
The proportion of dietary fat that is unsaturated fat with cis-trans isomerism such as omega-3 fatty acid and monounsaturated fats may be more important than the amount of dietary fat.[6]
## Atkins Diet (low carbohydrate)
The Atkins diet was developed by Dr. Robert Atkins' and intended to control blood sugar by reducing the number of carbohydrates consumed (particularly refined carbohydrates) while replacing them with significant quantities of fat and protein. The Atkins diet was originally designed for diabetes patients who wanted to manage their insulin levels more effectively. The short-term changes experienced by individuals on the Atkins diet include some rapid weight-loss as the body's glycogen stores were depleted, reducing fasting levels of triglycerides and an increasing blood-bound ketones. The diet also causes acidosis and mild fatigue.
## Mediterranean Diet
The Mediterranean diet emphasizes monounsaturated fats and may reduce cardiovascular disease.[7]
## Natural Diets
Since the advent of controversial diets such as Atkins, various diets that stress the eating habits of "natural humans" have been developed. The Paleolithic Diet imitates the way people ate during the Stone Age. These eating plans include basically natural foods (those not processed by humans). Whereas the Paleolithic Diet excludes milk and grain-foods, The Evolution Diet excludes human-made ingredients such as partially hydrogenated oils but allows some processed foods such as whole-grain crackers and dairy products. Anthropologists who focus their research on human evolution, however, are quick to point out that the diet of Paleolithic peoples was most likely opportunistic. That is, these early humans would most likely eat whatever edible foods were available at any given moment in that particular area (e.g. vegetables, termites, meat) and not restrict their intake of any food. Until recent human history, starvation has been a far greater threat than over-consumption.
## Time-Restricted Eating
Time-Restricted Eating may not be effective at weight loss[8].
## Vegetarian diet
There is a growing body of evidence that vegetarian diets can prevent obesity and lower disease risks.
According to the American Dietetic Association, "Vegetarians have been reported to have lower body mass indices than nonvegetarians, as well as lower rates of death from ischemic heart disease; vegetarians also show lower blood cholesterol levels; lower blood pressure; and lower rates of hypertension, type 2 diabetes, and prostate and colon cancer."
Vegetarians on average weigh 10 percent less than non-vegetarians. And in a year-long study comparing Dean Ornish's vegetarian diet to Weight Watchers, The Zone Diet, and The Atkins Diet, subjects on The Atkins Diet achieved the most weight loss (on average). Strict vegetarian diets like veganism may result in certain vitamin and mineral deficiencies if attention isn't paid to nutrition.
## Weight Watchers
Weight Watchers has two programs. The program offers a wide variety and foods. Each food has a point value. They encourage a well rounded diet, low in fat and high in fruits and vegetables. The core plan focuses more on portion control and natural foods. According to Weight Watchers, the act of keeping track of what one eats is very helpful in reducing overeating or eating for reasons other than hunger.
# Dangers of Dieting
Extreme calorie restriction, medication or unusual patterns of eating (i.e. restricting food consumption to a single fruit or meal) can be dangerous.
## ACC/AHA/ESC 2006 Guidelines for Management of Patients With Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death - Obesity, Dieting, and Anorexia (DO NOT EDIT) [9]
## Medications
Certain medications can be prescribed to assist in weight loss. Some, like amphetamines, are dangerous now banned for casual weight loss. Others, including those containing vitamins and minerals, are not effective for losing weight.
### Diuretics
Diuretics induce weight loss through the excretion of water. These medication or herbs will reduce the amount that a body weighs, but will have no effect on an individual's body fat. Diuretics can thicken the blood, cause cramping, kidney and liver damage.
### Stimulants
Stimulants such as ephedrine (now illegal in the United States due to an FDA ban) or synephrine work to increase the basal metabolic rate and reduce appetite. Stimulants can cause kidney and liver damage, sudden heart attacks, addiction, and ischemic strokes.[dubious – discuss]
In June 2006, the European Union approved the sale of the diet drug rimonabant, marketed under the trade name Acomplia. This new class of diet pills shows some promise in assisting physician-prescribed diets.[citation needed]
## Dangers of Fasting
Lengthy fasting can be dangerous due to the risk of malnutrition and should be carried out under medical supervision. During fasting, low-carbohydrate or very low calorie diets a lack of blood glucose, the preferred energy source of the brain, causes the body to metabolize sugars from protein, which can lead to muscle wasting.
## Side effects
Dieting, especially extreme food-intake reduction and rapid weight loss, can have the following side effects:
- Prolonged hunger
- Depression
- Reduced sex drive
- Fatigue
- Irritability
- Fainting
- Sinus problems (especially post-nasal drip)
- Muscle atrophy
- Rashes
- Acidosis
- Bloodshot eyes
- Gallbladder disease
- Seizures
- Weight gain on discontinuation
- Malnutrition, possibly leading to death
# Related Chapters
Template:Col-start
- Body image
- Crash diet
- Diet aid
- Dietitian
- Food faddism
- Healthy diet
- List of diets
- National Weight Control Registry
- Nutritional rating systems
- Nutrition scale
- Underweight
# External Links
Overeaters Anonymous | https://www.wikidoc.org/index.php/Atkins_diet | |
e51fc7dd9d55d1127058a7d44945918d9bd2f889 | wikidoc | Atresia | Atresia
Atresia is a condition in which a body orifice or passage in the body is abnormally closed or absent.
Examples of atresia include:
- Biliary atresia
- Ovarian follicle atresia, atresia refers to the degeneration and subsequent resorption of one or more immature ovarian follicles.
- Vaginal atresia - congenital occlusion of the vagina or subsequence adhesion (sticking together) of the walls of the vagina occluding it.
- Esophageal atresia - affects the alimentary tract causing the esophagus to end before connecting normally to the stomach.
- Choanal atresia - blockage of the back of the nasal passage, usually by abnormal bony or soft tissue.
- Anorectal atresia - malformation of the opening between the rectum and anus.
- Pulmonary atresia - malformation of the pulmonary valve in which the valve orifice fails to develop.
- Aural atresia (see Microtia) - a congenital deformity of the pinna (outer ear).
- Intestinal atresia - malformation of the intestine | Atresia
Atresia is a condition in which a body orifice or passage in the body is abnormally closed or absent.
Examples of atresia include:
- Biliary atresia
- Ovarian follicle atresia, atresia refers to the degeneration and subsequent resorption of one or more immature ovarian follicles.
- Vaginal atresia - congenital occlusion of the vagina or subsequence adhesion (sticking together) of the walls of the vagina occluding it.
- Esophageal atresia - affects the alimentary tract causing the esophagus to end before connecting normally to the stomach.
- Choanal atresia - blockage of the back of the nasal passage, usually by abnormal bony or soft tissue.
- Anorectal atresia - malformation of the opening between the rectum and anus.
- Pulmonary atresia - malformation of the pulmonary valve in which the valve orifice fails to develop.
- Aural atresia (see Microtia) - a congenital deformity of the pinna (outer ear).
- Intestinal atresia - malformation of the intestine | https://www.wikidoc.org/index.php/Atresia | |
732a647432cca8042c3d2239e6dcb113f5a2e086 | wikidoc | Atrophy | Atrophy
# Overview
Atrophy is the partial or complete wasting away of a part of the body. Causes of atrophy include poor nourishment, poor circulation, loss of hormonal support, loss of nerve supply to the target organ, disuse or lack of exercise or disease intrinsic to the tissue itself. Hormonal and nerve inputs that maintain an organ or body part are referred to as trophic.
Atrophy is a general physiological process of reabsorption and breakdown of tissues, involving apoptosis on a cellular level. When it occurs as a result of disease or loss of trophic support due to other disease, it is termed pathological atrophy, although it can be a part of normal body development and homeostasis as well.
# Types of Atrophy
## Normal Development
Examples of atrophy as part of normal development include shrinkage and involution of the thymus in early childhood and the tonsils in adolescence.
## Breast Atrophy
Atrophy of the breasts can occur with prolonged estrogen reduction, as with anorexia nervosa or menopause. Atrophy of the testes occurs with prolonged use of enough exogenous sex steroid (either androgen or estrogen) to reduce gonadotropin secretion. The adrenal glands atrophy during prolonged use of exogenous glucocorticoids like prednisone.
## Muscle Atrophy
Disuse atrophy of muscles (muscle atrophy) and bones, with loss of mass and strength, can occur after prolonged immobility, such as extended bedrest, or having a body part in a cast (living in darkness for the eye, bedridden for the legs, etc). This type of atrophy can usually be reversed with exercise unless severe. Astronauts must exercise regularly to minimize atrophy of their limb muscles while they are in microgravity.
There are many diseases and conditions which cause atrophy of muscle mass. For example diseases such as cancer and AIDS induce a body wasting syndrome called "cachexia", which is notable for the severe muscle atrophy seen. Other syndromes or conditions which can induce skeletal muscle atrophy are congestive heart failure and liver disease.
During aging, there is a gradual decrease in the ability to maintain skeletal muscle function and mass. This condition is called "sarcopenia", and may be distinct from atrophy in its pathophysiology. While the exact cause of sarcopenia is unknown, it may be induced by a combination of a gradual failure in the "satellite cells" which help to regenerate skeletal muscle fibers, and a decrease in sensitivity to or the availability of critical secreted growth factors which are necessary to maintain muscle mass and satellite cell survival.
## Dystrophies, Myosities, and Motor Neuron Conditions
Pathologic atrophy of muscles can occur due to diseases of the motor nerves, or due to diseases of the muscle tissue itself. Examples of atrophying nerve diseases include CMT (Charcot Marie Tooth syndrome) poliomyelitis, amyotrophic lateral sclerosis (ALS or Lou Gehrig's disease), and Guillain-Barre syndrome. Examples of atrophying muscle diseases include muscular dystrophy, myotonia congenita, and myotonic dystrophy.
## Vaginal Atrophy
In post-menopausal women, the walls of the vagina atrophy and become thinner. The mechanism for the age-related condition is not yet clear, though there are theories that the effect is caused by decreases in estrogen levels.
# Research
It has been reported that Astemizole might prevent 97% of the muscle wasting that occurs in immobile, bedridden patients.Testing upon mice showed that it blocked the activity of a protein present in the muscle that is involved in muscle atrophy. However the concerns for the drug's longterm effects on the heart preclude its routine use in humans for this indication and further alternative drugs are being sought.
# Related Chapters
- Olivopontocerebellar atrophy
- Optic atrophy
- Spinomuscular atrophy
- Testicular atrophy | Atrophy
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
# Overview
Atrophy is the partial or complete wasting away of a part of the body. Causes of atrophy include poor nourishment, poor circulation, loss of hormonal support, loss of nerve supply to the target organ, disuse or lack of exercise or disease intrinsic to the tissue itself. Hormonal and nerve inputs that maintain an organ or body part are referred to as trophic.
Atrophy is a general physiological process of reabsorption and breakdown of tissues, involving apoptosis on a cellular level. When it occurs as a result of disease or loss of trophic support due to other disease, it is termed pathological atrophy, although it can be a part of normal body development and homeostasis as well.
# Types of Atrophy
## Normal Development
Examples of atrophy as part of normal development include shrinkage and involution of the thymus in early childhood and the tonsils in adolescence.
## Breast Atrophy
Atrophy of the breasts can occur with prolonged estrogen reduction, as with anorexia nervosa or menopause. Atrophy of the testes occurs with prolonged use of enough exogenous sex steroid (either androgen or estrogen) to reduce gonadotropin secretion. The adrenal glands atrophy during prolonged use of exogenous glucocorticoids like prednisone.
## Muscle Atrophy
Disuse atrophy of muscles (muscle atrophy) and bones, with loss of mass and strength, can occur after prolonged immobility, such as extended bedrest, or having a body part in a cast (living in darkness for the eye, bedridden for the legs, etc). This type of atrophy can usually be reversed with exercise unless severe. Astronauts must exercise regularly to minimize atrophy of their limb muscles while they are in microgravity.
There are many diseases and conditions which cause atrophy of muscle mass. For example diseases such as cancer and AIDS induce a body wasting syndrome called "cachexia", which is notable for the severe muscle atrophy seen. Other syndromes or conditions which can induce skeletal muscle atrophy are congestive heart failure and liver disease.
During aging, there is a gradual decrease in the ability to maintain skeletal muscle function and mass. This condition is called "sarcopenia", and may be distinct from atrophy in its pathophysiology. While the exact cause of sarcopenia is unknown, it may be induced by a combination of a gradual failure in the "satellite cells" which help to regenerate skeletal muscle fibers, and a decrease in sensitivity to or the availability of critical secreted growth factors which are necessary to maintain muscle mass and satellite cell survival.[1]
## Dystrophies, Myosities, and Motor Neuron Conditions
Pathologic atrophy of muscles can occur due to diseases of the motor nerves, or due to diseases of the muscle tissue itself. Examples of atrophying nerve diseases include CMT (Charcot Marie Tooth syndrome) poliomyelitis, amyotrophic lateral sclerosis (ALS or Lou Gehrig's disease), and Guillain-Barre syndrome. Examples of atrophying muscle diseases include muscular dystrophy, myotonia congenita, and myotonic dystrophy.
## Vaginal Atrophy
In post-menopausal women, the walls of the vagina atrophy and become thinner. The mechanism for the age-related condition is not yet clear, though there are theories that the effect is caused by decreases in estrogen levels.[2]
# Research
It has been reported that Astemizole might prevent 97% of the muscle wasting that occurs in immobile, bedridden patients.[3]Testing upon mice showed that it blocked the activity of a protein present in the muscle that is involved in muscle atrophy.[4] However the concerns for the drug's longterm effects on the heart preclude its routine use in humans for this indication and further alternative drugs are being sought.[3]
# Related Chapters
- Olivopontocerebellar atrophy
- Optic atrophy
- Spinomuscular atrophy
- Testicular atrophy | https://www.wikidoc.org/index.php/Atrophic | |
2d98a2b5d4bd737573a4a61d0a0f8ccf54cadd61 | wikidoc | Autopsy | Autopsy
# Overview
An autopsy, also known as a post-mortem examination, necropsy, or obduction, is a medical procedure that consists of a thorough examination of a corpse to determine the cause and manner of death and to evaluate any disease or injury that may be present. It is usually performed by a specialized medical doctor called a pathologist.
Autopsies are either performed for legal or medical purposes. A forensic autopsy is carried out when the cause of death may be a criminal matter, while a clinical or academic autopsy is performed to find the medical cause of death and is used in cases of unknown or uncertain death, or for research purposes. Autopsies can be further classified into cases where external examination suffices, and those where the body is dissected and an internal examination is conducted. Permission from next of kin may be required for internal autopsy in some cases. Once an internal autopsy is complete the body is reconstituted by sewing it back together.
Necropsy is the term for a post-mortem examination performed on an animal. The prefix 'auto-' means 'self', and so autopsy denotes the human species performing a post-mortem examination on one of its own.
# Value of autopsy in medicine
Autopsies are important in clinical medicine as they often shed light on medical error and can be used to help guide continuous improvement.
A study that focused on myocardial infarction (heart attack) as a cause of death found significant errors of omission and commission, i.e. a sizable number cases ascribed to myocardial infarctions (MIs) were not MIs and a significant number of non-MIs were actually MIs.
A systematic review of studies of the autopsy calculated that in about 25% of autopsies a major diagnostic error will be revealed. However, this rate has decreased over time and the study projects that in a contemporary US institution, 8.4% to 24.4% of autopsies will detect major diagnostic errors.
A large meta-analysis suggested that approximately one third of death certificates are incorrect and that half of the autopsies performed produced findings that were not suspected before the person died. Also, it is thought that over one fifth of unexpected findings can only be diagnosed histologically, i.e. by biopsy or autopsy, and that approximately one quarter of unexpected findings, or 5% of all findings, are major and can similarly only be diagnosed from tissue.
## Value of autopsy in intensive care unit
One study found 32% major diagnositic errors (Class I and Class II) with the leading missed diagnoses being "Autopsies revealed 171 missed diagnoses, including 21 cancers, 12 strokes, 11 myocardial infarctions, 10 pulmonary emboli, and 9 endocarditis, among others".
Focusing intubated patients, one study found "abdominal pathologic conditions--abscesses, bowel perforations, or infarction--were as frequent as pulmonary emboli as a cause of class I errors. While patients with abdominal pathologic conditions generally complained of abdominal pain, results of examination of the abdomen were considered unremarkable in most patients, and the symptom was not pursued".
# General information
The term "autopsy" derives from the Greek for "to see for oneself". "Necropsy" is from the Greek for "seeing a dead body".
There are four main types of autopsies:
- Forensic: This is done for medical-legal purposes, and is the one that is normally seen on television or in the news. This type depict an extensive methodology and tends to be complete and comprehensive. No family permission is required to complete this type of autopsy.
- Clinical/academic: This is usually performed in hospitals to for research and study purposes. For a clinical autopsy to take place a cause of death must have already been established and a death certificate completed. This usually is as comprehensive as it needs to be adequate. To complete this type of autopsy, permission from the deceased's legal next of kin is required.
- Coroner's: In Great Britain this type of autopsy encompasses cases where no medical cause of death is readily available. Cause, manner and mechanism of death are in question. Eventually, the prosectors will identify whether the cases deserve comprehensive forensic autopsy or a routine postmortem. In the United States, each state has a set of guidelines defining a "coroner's case" for autopsy, for example: hospital deaths occurring within 24 hours of admission or within 24 hours of a major surgical procedure, with any history (current or remote) of illegal drug or alcohol abuse by the deceased, patients with certain communicable diseases (HIV, hepatitis C virus, etc.), patients with any previous history of violent injury (e.g., gunshot wound many years before death). These cases may or may not be also considered "forensic" in nature. They may be done by the hospital pathologist with the legal permission of the coroner or medical examiner for that county/parish and do not require permission from the deceased's legal next of kin.
- Virtual Autopsy: This is when the autopsy is performed entirely by medical imaging, primarily CT and MRI
While dissection of human remains for medical reasons has been practised irregularly for millennia, the modern autopsy process derives from the anatomists of the Renaissance. The two great nineteenth-century medical researchers Rudolf Virchow and Carl von Rokitansky built on the Renaissance legacy to derive the two distinct autopsy techniques that still bear their names. Their demonstration of correspondences between pathological conditions in dead bodies and symptoms and illnesses in the living opened the way for a different way of thinking about disease and its treatment. In China, the office of coroner and forensic autopsy have a history nearly two thousand years old.
# Forensic autopsy
A forensic autopsy is used to determine the cause of death. Forensic science involves the application of the sciences to answer questions of interest to the legal system. In United States law, deaths are placed in one of five manners:
- Natural
- Accident
- Homicide
- Suicide
- Undetermined
In some jurisdictions, the Undetermined category may include deaths in absentia, such as deaths at sea and missing persons declared dead in a court of law; in others, such deaths are classified under "Other".
Following an in-depth examination of all the evidence, a medical examiner or coroner will assign a manner of death as one of the five listed above; and detail the evidence on the mechanism of the death.
# Clinical autopsy
Clinical autopsies serve two major purposes. They are performed to gain more insight into pathological processes and determine what factors contributed to a patient's death. More importantly, autopsies are performed to ensure the standard of care at hospitals. Autopsies can yield insight into how patient deaths can be prevented in the future.
Within the United Kingdom, clinical autopsies can only be carried out with the consent of the family of the deceased person as opposed to a medico-legal autopsy instructed by a Coroner (England & Wales) or Procurator Fiscal (Scotland) to which the family cannot object.
# The process
The body is received at a medical examiner's office or hospital in a body bag or evidence sheet. A brand new body bag is used for each body to ensure that only evidence from that body is contained within the bag. Evidence sheets are an alternate way to transport the body. An evidence sheet is a sterile sheet that the body is covered in when it is moved. If it is believed there may be any significant residue on the hands, for instance gunpowder, a separate paper sack is put around each hand and taped shut around the wrist.
There are two parts to the physical examination of the body: the external and internal examination. Toxicology, biochemical tests and/or genetic testing often supplement these and frequently assist the pathologist in assigning the cause or causes of death.
## External examination
The person responsible for handling, cleaning and moving the body is often called a diener, the German word for servant. In the UK this role is performed by an Anatomical Pathology Technologist who will also assist the pathologist in eviscerating the deceased and reconstruction after the autopsy. After the body is received, it is first photographed. The examiner then notes the kind of clothes and their position on the body before they are removed. Next, any evidence such as residue, flakes of paint or other material is collected from the external surfaces of the body. Ultraviolet light may also be used to search body surfaces for any evidence not easily visible to the naked eye. Samples of hair, nails and the like are taken, and the body may also be radiographically imaged.
Once the external evidence is collected, the body is removed from the bag, undressed and any wounds present are examined. The body is then cleaned, weighed and measured in preparation for the internal examination. The scale used to weigh the body is often designed to accommodate the cart that the body is transported on; its weight is then deducted from the total weight shown to give the weight of the body.
If not already within an autopsy room, the body is transported to one and placed on a table. A general description of the body as regards race, sex, age, hair color and length, eye color and other distinguishing features (birthmarks, old scar tissue, moles, etc) is then made. A handheld voice recorder or a standard examination form is normally used to record this information.
In some countries e.g. France, Germany and Canada to name but a few, an autopsy may comprise an external examination only. This concept is sometimes termed a "view and grant". The principles behind this being that the medical records, history of the deceased and circumstances of death have all indicated as to the cause and manner of death without the need for an internal examination.
## Internal examination
If not already in place, a plastic or rubber brick called a "body block" is placed under the back of the body, causing the arms and neck to fall backward whilst stretching and pushing the chest upward to make it easier to cut open. This gives the prosector, a pathologist or assistant, maximum exposure to the trunk. After this is done, the internal examination begins. The internal examination consists of inspecting the internal organs of the body for evidence of trauma or other indications of the cause of death. For the internal examination there are a number of different approaches available:
- a large and deep Y-shaped incision can be made from behind each ear and running down the sides of the neck, meeting at the breastbone. This is the approach most often used in forensic autopsies so as to allow maximum exposure of the neck structures for later detailed examination. This could prove essential in cases of suspected strangulation
- a T-shaped incision made from the tips of both shoulder, in a horizontal line across the region of the collar bones to meet at the sternum (breastbone) in the middle. This initial cut is used more often to produce a more aesthetic finish to the body when it is re-constituted as stitching marks will not be as apparent as with a Y-shaped incision
- a single vertical cut is made from the middle of the neck (in the region of the 'adam's apple' on a male body)
In all of the above cases the cut then extends all the way down to the pubic bone (making a deviation to the left side of the navel).
Bleeding from the cuts is minimal, or non-existent, due to the fact that the pull of gravity is producing the only blood pressure at this point, related directly to the complete lack of cardiac functionality. However, in certain cases there is anecdotal evidence to prove that bleeding can be quite profuse, especially in cases of drowning.
An electric saw dubbed a "Stryker saw" after a common manufacturer of the tool, is most often used to open the chest cavity. However, in some cases, due to the large amount of dust created when the bone is cut by the saw, shears are used to open the chest cavity. It is also possible to utilise a simple scalpel blade. The prosector uses the tool to saw through the ribs on the lateral sides of the chest cavity to allow the sternum and attached ribs to be lifted as one chest plate; this is done so that the heart and lungs can be seen in situ and that the heart, in particular the pericardial sac is not damaged or disturbed from opening. A scalpel is used to remove any soft tissue that is still attached to the posterior side of the chest plate. Now the lungs and the heart are exposed. The chest plate is set aside and will be eventually replaced at the end of the autopsy.
At this stage the organs are exposed. Usually, the organs are removed in a systematic fashion. Making a decision as to what order the organs are to be removed will depend highly on the case in question. Organs can be removed in several ways: The first is the en masse technique of letulle whereby all the organs are removed as one large mass. The second is the en bloc method of Ghon. The most popular in the UK is a modified version of this method which is divided into four groups of organs. Although these are the two predominant evisceration techniques in the UK variations on these are widespread.
One method is described here:
The pericardial sac is opened to view the heart. Blood for chemical analysis may be removed from the inferior vena cava or the pulmonary veins. Before removing the heart, the pulmonary artery is opened in order to search for a blood clot. The heart can then be removed by cutting the inferior vena cava, the pulmonary veins, the aorta and pulmonary artery, and the superior vena cava. This method leaves the aortic arch intact, which will make things easier for the embalmer. The left lung is then easily accessible and can be removed by cutting the bronchus, artery, and vein at the hilum. The right lung can then be similarly removed. The abdominal organs can be removed one by one after first examining their relationships and vessels.
Some pathologists, however, prefer to remove the organs all in one "block". Then a series of cuts, along the vertebral column, are made so that the organs can be detached and pulled out in one piece for further inspection and sampling. During autopsies of infants, this method is used almost all of the time. The various organs are examined, weighed and tissue samples in the form of slices are taken. Even major blood vessels are cut open and inspected at this stage. Next the stomach and intestinal contents are examined and weighed. This could be useful to find the cause and time of death, due to the natural passage of food through the bowel during digestion. The more area empty, the longer the deceased had gone without a meal before death.
The body block that was used earlier to elevate the chest cavity is now used to elevate the head. To examine the brain, a cut is made from behind one ear, over the crown of the head, to a point behind the other ear. When the autopsy is completed, the incision can be neatly sewn up and is not noticed when the head is resting on a pillow in an open casket funeral. The scalp is pulled away from the skull in two flaps with the front flap going over the face and the rear flap over the back of the neck. The skull is then cut with an electric saw to create a "cap" that can be pulled off, exposing the brain. The brain is then observed in situ. Then the brain's connection to the spinal cord is severed, and the brain is then lifted out of the skull for further examination. If the brain needs to be preserved before being inspected, it is contained in a large container of formalin (15 percent solution of formaldehyde gas in buffered water) for at least two but preferably four weeks. This not only preserves the brain, but also makes it firmer allowing easier handling without corrupting the tissue.
# Reconstitution of the body
An important component of the autopsy is the reconstitution of the body such that it can be viewed, if desired, by relatives of the deceased following the procedure. After the examination, the body has an open and empty chest cavity with chest flaps open on both sides, the top of the skull is missing, and the skull flaps are pulled over the face and neck. It is unusual to examine the face, arms, hands or legs internally. In the UK, following the Human Tissue Act 2004 all organs and tissue must be returned to the body unless permission is given by the family to retain any tissue for further investigation. Normally the internal body cavity is lined with cotton wool or an appropriate material, the organs are then placed into a plastic bag to prevent leakage and returned to the body cavity. The chest flaps are then closed and sewn back together and the skull cap is sewed back in place. Then the body may be wrapped in a shroud and it is common for relatives of the deceased to not be able to tell the procedure has been done when the deceased is viewed in a funeral parlor after embalming.
# Other information
The principal aim of an autopsy is to determine the cause of death, the state of health of the person before he or she died, and whether any medical diagnosis and treatment before death was appropriate.
In most Western countries the number of autopsies performed in hospitals has been decreasing every year since 1955. Critics, including pathologist and former JAMA editor George Lundberg, have charged that the reduction in autopsies is negatively affecting the care delivered in hospitals, because when mistakes result in death, they are often not investigated and lessons learned.
When a person has given permission in advance of their death, autopsies may also be carried out for the purposes of teaching or medical research.
An autopsy is frequently performed in cases of sudden death, where a doctor is not able to write a death certificate, or when death is believed to be due to an unnatural cause. These examinations are performed under a legal authority (Medical Examiner or Coroner or Procurator Fiscal) and do not require the consent of relatives of the deceased. The most extreme example is the examination of murder victims, especially when medical examiners are looking for signs of death or the murder method, such as bullet wounds and exit points, signs of strangulation, or traces of poison. | Autopsy
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
# Overview
An autopsy, also known as a post-mortem examination, necropsy, or obduction, is a medical procedure that consists of a thorough examination of a corpse to determine the cause and manner of death and to evaluate any disease or injury that may be present. It is usually performed by a specialized medical doctor called a pathologist.
Autopsies are either performed for legal or medical purposes. A forensic autopsy is carried out when the cause of death may be a criminal matter, while a clinical or academic autopsy is performed to find the medical cause of death and is used in cases of unknown or uncertain death, or for research purposes. Autopsies can be further classified into cases where external examination suffices, and those where the body is dissected and an internal examination is conducted. Permission from next of kin may be required for internal autopsy in some cases. Once an internal autopsy is complete the body is reconstituted by sewing it back together.
Necropsy is the term for a post-mortem examination performed on an animal. The prefix 'auto-' means 'self', and so autopsy denotes the human species performing a post-mortem examination on one of its own.
# Value of autopsy in medicine
Autopsies are important in clinical medicine as they often shed light on medical error and can be used to help guide continuous improvement.
A study that focused on myocardial infarction (heart attack) as a cause of death found significant errors of omission and commission,[1] i.e. a sizable number cases ascribed to myocardial infarctions (MIs) were not MIs and a significant number of non-MIs were actually MIs.
A systematic review of studies of the autopsy calculated that in about 25% of autopsies a major diagnostic error will be revealed.[2] However, this rate has decreased over time and the study projects that in a contemporary US institution, 8.4% to 24.4% of autopsies will detect major diagnostic errors.
A large meta-analysis suggested that approximately one third of death certificates are incorrect and that half of the autopsies performed produced findings that were not suspected before the person died.[3] Also, it is thought that over one fifth of unexpected findings can only be diagnosed histologically, i.e. by biopsy or autopsy, and that approximately one quarter of unexpected findings, or 5% of all findings, are major and can similarly only be diagnosed from tissue.
## Value of autopsy in intensive care unit
One study found 32% major diagnositic errors (Class I and Class II) with the leading missed diagnoses being "Autopsies revealed 171 missed diagnoses, including 21 cancers, 12 strokes, 11 myocardial infarctions, 10 pulmonary emboli, and 9 endocarditis, among others".[4]
Focusing intubated patients, one study found "abdominal pathologic conditions--abscesses, bowel perforations, or infarction--were as frequent as pulmonary emboli as a cause of class I errors. While patients with abdominal pathologic conditions generally complained of abdominal pain, results of examination of the abdomen were considered unremarkable in most patients, and the symptom was not pursued".[5]
# General information
The term "autopsy" derives from the Greek for "to see for oneself". "Necropsy" is from the Greek for "seeing a dead body".
There are four main types of autopsies:
- Forensic: This is done for medical-legal purposes, and is the one that is normally seen on television or in the news. This type depict an extensive methodology and tends to be complete and comprehensive. No family permission is required to complete this type of autopsy.
- Clinical/academic: This is usually performed in hospitals to for research and study purposes. For a clinical autopsy to take place a cause of death must have already been established and a death certificate completed. This usually is as comprehensive as it needs to be adequate. To complete this type of autopsy, permission from the deceased's legal next of kin is required.
- Coroner's: In Great Britain this type of autopsy encompasses cases where no medical cause of death is readily available. Cause, manner and mechanism of death are in question. Eventually, the prosectors will identify whether the cases deserve comprehensive forensic autopsy or a routine postmortem. In the United States, each state has a set of guidelines defining a "coroner's case" for autopsy, for example: hospital deaths occurring within 24 hours of admission or within 24 hours of a major surgical procedure, with any history (current or remote) of illegal drug or alcohol abuse by the deceased, patients with certain communicable diseases (HIV, hepatitis C virus, etc.), patients with any previous history of violent injury (e.g., gunshot wound many years before death). These cases may or may not be also considered "forensic" in nature. They may be done by the hospital pathologist with the legal permission of the coroner or medical examiner for that county/parish and do not require permission from the deceased's legal next of kin.
- Virtual Autopsy: This is when the autopsy is performed entirely by medical imaging, primarily CT and MRI[6]
While dissection of human remains for medical reasons has been practised irregularly for millennia, the modern autopsy process derives from the anatomists of the Renaissance. The two great nineteenth-century medical researchers Rudolf Virchow and Carl von Rokitansky built on the Renaissance legacy to derive the two distinct autopsy techniques that still bear their names. Their demonstration of correspondences between pathological conditions in dead bodies and symptoms and illnesses in the living opened the way for a different way of thinking about disease and its treatment. In China, the office of coroner and forensic autopsy have a history nearly two thousand years old.
# Forensic autopsy
A forensic autopsy is used to determine the cause of death. Forensic science involves the application of the sciences to answer questions of interest to the legal system. In United States law, deaths are placed in one of five manners:
- Natural
- Accident
- Homicide
- Suicide
- Undetermined
In some jurisdictions, the Undetermined category may include deaths in absentia, such as deaths at sea and missing persons declared dead in a court of law; in others, such deaths are classified under "Other".
Following an in-depth examination of all the evidence, a medical examiner or coroner will assign a manner of death as one of the five listed above; and detail the evidence on the mechanism of the death.
# Clinical autopsy
Clinical autopsies serve two major purposes. They are performed to gain more insight into pathological processes and determine what factors contributed to a patient's death. More importantly, autopsies are performed to ensure the standard of care at hospitals. Autopsies can yield insight into how patient deaths can be prevented in the future.
Within the United Kingdom, clinical autopsies can only be carried out with the consent of the family of the deceased person as opposed to a medico-legal autopsy instructed by a Coroner (England & Wales) or Procurator Fiscal (Scotland) to which the family cannot object.
# The process
The body is received at a medical examiner's office or hospital in a body bag or evidence sheet. A brand new body bag is used for each body to ensure that only evidence from that body is contained within the bag. Evidence sheets are an alternate way to transport the body. An evidence sheet is a sterile sheet that the body is covered in when it is moved. If it is believed there may be any significant residue on the hands, for instance gunpowder, a separate paper sack is put around each hand and taped shut around the wrist.
There are two parts to the physical examination of the body: the external and internal examination. Toxicology, biochemical tests and/or genetic testing often supplement these and frequently assist the pathologist in assigning the cause or causes of death.
## External examination
The person responsible for handling, cleaning and moving the body is often called a diener, the German word for servant. In the UK this role is performed by an Anatomical Pathology Technologist who will also assist the pathologist in eviscerating the deceased and reconstruction after the autopsy. After the body is received, it is first photographed. The examiner then notes the kind of clothes and their position on the body before they are removed. Next, any evidence such as residue, flakes of paint or other material is collected from the external surfaces of the body. Ultraviolet light may also be used to search body surfaces for any evidence not easily visible to the naked eye. Samples of hair, nails and the like are taken, and the body may also be radiographically imaged.
Once the external evidence is collected, the body is removed from the bag, undressed and any wounds present are examined. The body is then cleaned, weighed and measured in preparation for the internal examination. The scale used to weigh the body is often designed to accommodate the cart that the body is transported on; its weight is then deducted from the total weight shown to give the weight of the body.
If not already within an autopsy room, the body is transported to one and placed on a table. A general description of the body as regards race, sex, age, hair color and length, eye color and other distinguishing features (birthmarks, old scar tissue, moles, etc) is then made. A handheld voice recorder or a standard examination form is normally used to record this information.
In some countries e.g. France, Germany and Canada to name but a few, an autopsy may comprise an external examination only. This concept is sometimes termed a "view and grant". The principles behind this being that the medical records, history of the deceased and circumstances of death have all indicated as to the cause and manner of death without the need for an internal examination.
## Internal examination
If not already in place, a plastic or rubber brick called a "body block" is placed under the back of the body, causing the arms and neck to fall backward whilst stretching and pushing the chest upward to make it easier to cut open. This gives the prosector, a pathologist or assistant, maximum exposure to the trunk. After this is done, the internal examination begins. The internal examination consists of inspecting the internal organs of the body for evidence of trauma or other indications of the cause of death. For the internal examination there are a number of different approaches available:
- a large and deep Y-shaped incision can be made from behind each ear and running down the sides of the neck, meeting at the breastbone. This is the approach most often used in forensic autopsies so as to allow maximum exposure of the neck structures for later detailed examination. This could prove essential in cases of suspected strangulation
- a T-shaped incision made from the tips of both shoulder, in a horizontal line across the region of the collar bones to meet at the sternum (breastbone) in the middle. This initial cut is used more often to produce a more aesthetic finish to the body when it is re-constituted as stitching marks will not be as apparent as with a Y-shaped incision
- a single vertical cut is made from the middle of the neck (in the region of the 'adam's apple' on a male body)
In all of the above cases the cut then extends all the way down to the pubic bone (making a deviation to the left side of the navel).
Bleeding from the cuts is minimal, or non-existent, due to the fact that the pull of gravity is producing the only blood pressure at this point, related directly to the complete lack of cardiac functionality. However, in certain cases there is anecdotal evidence to prove that bleeding can be quite profuse, especially in cases of drowning.
An electric saw dubbed a "Stryker saw" after a common manufacturer of the tool, is most often used to open the chest cavity. However, in some cases, due to the large amount of dust created when the bone is cut by the saw, shears are used to open the chest cavity. It is also possible to utilise a simple scalpel blade. The prosector uses the tool to saw through the ribs on the lateral sides of the chest cavity to allow the sternum and attached ribs to be lifted as one chest plate; this is done so that the heart and lungs can be seen in situ and that the heart, in particular the pericardial sac is not damaged or disturbed from opening. A scalpel is used to remove any soft tissue that is still attached to the posterior side of the chest plate. Now the lungs and the heart are exposed. The chest plate is set aside and will be eventually replaced at the end of the autopsy.
At this stage the organs are exposed. Usually, the organs are removed in a systematic fashion. Making a decision as to what order the organs are to be removed will depend highly on the case in question. Organs can be removed in several ways: The first is the en masse technique of letulle whereby all the organs are removed as one large mass. The second is the en bloc method of Ghon. The most popular in the UK is a modified version of this method which is divided into four groups of organs. Although these are the two predominant evisceration techniques in the UK variations on these are widespread.
One method is described here:
The pericardial sac is opened to view the heart. Blood for chemical analysis may be removed from the inferior vena cava or the pulmonary veins. Before removing the heart, the pulmonary artery is opened in order to search for a blood clot. The heart can then be removed by cutting the inferior vena cava, the pulmonary veins, the aorta and pulmonary artery, and the superior vena cava. This method leaves the aortic arch intact, which will make things easier for the embalmer. The left lung is then easily accessible and can be removed by cutting the bronchus, artery, and vein at the hilum. The right lung can then be similarly removed. The abdominal organs can be removed one by one after first examining their relationships and vessels.
Some pathologists, however, prefer to remove the organs all in one "block". Then a series of cuts, along the vertebral column, are made so that the organs can be detached and pulled out in one piece for further inspection and sampling. During autopsies of infants, this method is used almost all of the time. The various organs are examined, weighed and tissue samples in the form of slices are taken. Even major blood vessels are cut open and inspected at this stage. Next the stomach and intestinal contents are examined and weighed. This could be useful to find the cause and time of death, due to the natural passage of food through the bowel during digestion. The more area empty, the longer the deceased had gone without a meal before death.
The body block that was used earlier to elevate the chest cavity is now used to elevate the head. To examine the brain, a cut is made from behind one ear, over the crown of the head, to a point behind the other ear. When the autopsy is completed, the incision can be neatly sewn up and is not noticed when the head is resting on a pillow in an open casket funeral. The scalp is pulled away from the skull in two flaps with the front flap going over the face and the rear flap over the back of the neck. The skull is then cut with an electric saw to create a "cap" that can be pulled off, exposing the brain. The brain is then observed in situ. Then the brain's connection to the spinal cord is severed, and the brain is then lifted out of the skull for further examination. If the brain needs to be preserved before being inspected, it is contained in a large container of formalin (15 percent solution of formaldehyde gas in buffered water) for at least two but preferably four weeks. This not only preserves the brain, but also makes it firmer allowing easier handling without corrupting the tissue.
# Reconstitution of the body
An important component of the autopsy is the reconstitution of the body such that it can be viewed, if desired, by relatives of the deceased following the procedure. After the examination, the body has an open and empty chest cavity with chest flaps open on both sides, the top of the skull is missing, and the skull flaps are pulled over the face and neck. It is unusual to examine the face, arms, hands or legs internally. In the UK, following the Human Tissue Act 2004 all organs and tissue must be returned to the body unless permission is given by the family to retain any tissue for further investigation. Normally the internal body cavity is lined with cotton wool or an appropriate material, the organs are then placed into a plastic bag to prevent leakage and returned to the body cavity. The chest flaps are then closed and sewn back together and the skull cap is sewed back in place. Then the body may be wrapped in a shroud and it is common for relatives of the deceased to not be able to tell the procedure has been done when the deceased is viewed in a funeral parlor after embalming.
# Other information
The principal aim of an autopsy is to determine the cause of death, the state of health of the person before he or she died, and whether any medical diagnosis and treatment before death was appropriate.
In most Western countries the number of autopsies performed in hospitals has been decreasing every year since 1955. Critics, including pathologist and former JAMA editor George Lundberg, have charged that the reduction in autopsies is negatively affecting the care delivered in hospitals, because when mistakes result in death, they are often not investigated and lessons learned.
When a person has given permission in advance of their death, autopsies may also be carried out for the purposes of teaching or medical research.
An autopsy is frequently performed in cases of sudden death, where a doctor is not able to write a death certificate, or when death is believed to be due to an unnatural cause. These examinations are performed under a legal authority (Medical Examiner or Coroner or Procurator Fiscal) and do not require the consent of relatives of the deceased. The most extreme example is the examination of murder victims, especially when medical examiners are looking for signs of death or the murder method, such as bullet wounds and exit points, signs of strangulation, or traces of poison. | https://www.wikidoc.org/index.php/Autopsies | |
e060801947abdabc3d5ff801abee0e25703a863a | wikidoc | Auxilin | Auxilin
Putative tyrosine-protein phosphatase auxilin is an enzyme that in humans is encoded by the DNAJC6 gene.
# Function
DNAJC6 belongs to the evolutionarily conserved DNAJ/HSP40 family of proteins, which regulate molecular chaperone activity by stimulating ATPase activity. DNAJ proteins may have up to 3 distinct domains: a conserved 70-amino acid J domain, usually at the N terminus, a glycine/phenylalanine (G/F)-rich region, and a cysteine-rich domain containing 4 motifs resembling a zinc-finger domain (Ohtsuka and Hata, 2000).
# Structure
The protein tyrosine phosphatase domain and C2 domain pair of auxilin, located near the N-terminus of the polypeptide, constitute a superdomain, a tandem arrangement of two or more nominally unrelated domains that form a single heritable unit. The phosphatase domain belongs to the auxilin subfamily of lipid phosphatases and is predicted to be catalytically inactive. | Auxilin
Putative tyrosine-protein phosphatase auxilin is an enzyme that in humans is encoded by the DNAJC6 gene.[1][2][3]
# Function
DNAJC6 belongs to the evolutionarily conserved DNAJ/HSP40 family of proteins, which regulate molecular chaperone activity by stimulating ATPase activity. DNAJ proteins may have up to 3 distinct domains: a conserved 70-amino acid J domain, usually at the N terminus, a glycine/phenylalanine (G/F)-rich region, and a cysteine-rich domain containing 4 motifs resembling a zinc-finger domain (Ohtsuka and Hata, 2000).[3]
# Structure
The protein tyrosine phosphatase domain and C2 domain pair of auxilin, located near the N-terminus of the polypeptide, constitute a superdomain, a tandem arrangement of two or more nominally unrelated domains that form a single heritable unit.[4] The phosphatase domain belongs to the auxilin subfamily of lipid phosphatases and is predicted to be catalytically inactive. [5] | https://www.wikidoc.org/index.php/Auxilin | |
5311b585beaa84002e0b865c68ecc1a80ad75e46 | wikidoc | Average | Average
# Overview
In mathematics, an average, or central tendency of a data set refers to a measure of the "middle" or "expected" value of the data set. There are many different descriptive statistics that can be chosen as a measurement of the central tendency of the data items. The most common method is the arithmetic mean, but there are many other types of averages.
Colloquially, people often use the term average to refer to an intuitive central tendency without having a specific measurement of central tendency in mind, or use terms such as "the average person". However, the phrase "there's no such thing as an average citizen" emphasizes that the average is a number, not a person or some other object. The average is calculated by combining the measurements related to a group of people or objects, to compute a number as being the average of the group.
Please see the table of mathematical symbols for explanations of the symbols used. In statistics, the term central tendency is used in some fields of empirical research to refer to what statisticians sometimes call "location". A "measure of central tendency" is either a location parameter or a statistic used to estimate a location parameter.
# Calculating averages
An average is a representative value of a list. If all the numbers in the list were the same, then this number should be used. What if they are not the same? There are many different possible answers to this question. The average should not depend on the order of the numbers in the list, and it is often useful to also require that it should not be less than the smaller number in the list, nor greater than the greater number in the list (but see the annualiztion of of returns for other than one year in duration).
An easy way to get a representative value from a list is to randomly pick any number from the list. However, the word 'average' is usually reserved for more sophisticated methods that are generally found to be more useful.
The most common type of average is the arithmetic mean, often simply called the mean. The arithmetic mean of two numbers, such as 2 and 8, is obtained by finding a value A such that 2 + 8 = A + A. It is then simple to find that A = (2 + 8)/2 = 5. Switching the order of 2 and 8 to read 8 and 2 does not change the resulting value obtained for A. The mean 5 is not less than the minimum 2 nor greater than the maximum 8. If we increase the number of terms in the list for which we want an average, we get, for example, that the arithmetic mean of 2, 8, and 11 is found by solving for the value of A in the equation 2 + 8 + 11 = A + A + A. It is simple to find that A = (2 + 8 + 11)/3 = 7. Again we see that changing the order of the three members of the list does not change the result: A = (8 + 11 + 2)/3 = 7, and that 7 is between 2 and 11. This summation method is easily generalized for lists with any number of elements. It is also easy to see that the mean of a list of integers is not necessarily an integer. "The average family has 1.7 children" is an unpleasant way of expressing that the average number of children in some list of families is 1.7. The temperature represented by the arithmetic mean of a list of temperatures does not depend on whether the Fahrenheit or the Celcius scale is used, and this is one reason why an 'average temperature' is useful.
There are many other kinds of averages. However, they can all be understood in the same manner. For example, sometimes it is informative to consider the geometric mean. Here, instead of adding numbers we multiply them. Thus, the geometric mean of 2 and 8 is obtained by solving for G in the following equation: 2 - 8 = G - G. Thus, the geometric mean of 2 and 8 is G = sqrt(2 - 8) = 4. And again it is seen that changing the order of the members of the list to be averaged does not change the result: G = sqrt(8 - 2) = 4. In order to make sense of the requirement that the mean must be at least as big as the smallest member of the list and no bigger than the largest, the geometric mean is usually only applied to lists of positive numbers, not to lists that can include negative numbers such as temperatures.
It should now be obvious that it would be easy to come up with many other ways of combining the elements of a list in a manner that does not change when the order of the list is changed. For each of them one can define an average based on that method.
The most frequently occurring number in a list of numbers is called the mode. So the mode of the list (1, 2, 2, 3, 3, 3, 4) is 3. The mode is not necessarily well defined. The list (1, 2, 2, 3, 3, 5) has the two modes 2 and 3. The mode can be subsumed under the general method of defining averages by understanding it as taking the list and setting each member of the list equal to the most common value in the list if there is a most common value. This list is then equated to a the resulting list with all values replaced by the same value. Since they are already all the same, this does not require any change.
Another average worth discussing is the median. Its method is to order the list according to its magnitude and then repeatedly remove the pair consisting of the highest and lowest value till either one or two values are left. If two values are left replace them with their arithmetic mean. This method takes the list 1, 7, 3, 13 and orders it to read 1, 3, 7, 13. Then the 1 and 13 are removed to obtain the list 3, 7. Since there are two elements in this list replace them by their arithmetic mean (3 + 7)/2 = 5. Now do the same for the equal sized list consisting of all the same value M: M, M, M, M. It is already ordered. We remove the two end values to get M, M. We take their arithmetic mean to get M. Finally, set this result equal to our previous result to get M = 5.
In finance people are often interested in the annualized return which is a different kind of average. To begin with an example consider two years in which the return in the first year is minus 10% and the return in the second year is plus 60%. Then the annualized return, R, would be obtained by solving the equation: (1 - 10%) - (1 + 60%) = (1 + R) - (1 + R). The value of R that makes this equation true is R = 12%. It is again to be noted that changing the order to find the annualized return of 60% and -10% gives the same result as the annualized return of -10% and 60%. This method can be generalized to examples where the periods are not all of one-year duration. Annualization of a set of returns is a variation on the geometric average that provides the intensive property of a return per year corresponding to a list of returns. Consider a function that adds one to each return in the list and then takes the T th root of their product, where T is the sum of the periods of all the returns. This function is set equal to the same function for a list with the same number of elements composed of identical single year returns, whose value is the annualized return. For example, consider a period of a half of a year for which the return is minus 20% and a period of two and one half years for which the return is 116%. The annualized return for the combined period is the single year return, R, that is the solution of the following equation:
{(1-20%)*(1+116%)}^{1/(0.5 + 2.5)} = {(1+R)*(1+R)}^{1/(1 + 1)},
giving an annualized return, R, of 20%.
The Heronian mean H, is obtained by taking the sum of the square root of the product of each paired combination of two members of a list. Since the pairs are created by all ways of picking twice from the list while ignoring the order, the pair (a,c) is picked only once since (a,c) is the same as (c,a). However, the same element of the list can be picked twice within a single pair to get (a,a). Also, since it is the element on the list that is picked, not the value, if the same value appears twice on the list, different ways of picking it are included. Therefore, if the list has three members, designated a, b, c, then set sqrt(a*a) + sqrt(a*b) + sqrt(a*c) + sqrt(b*b) + sqrt(b*c) + sqrt(c*c) equal to sqrt(H*H) + sqrt(H*H) + sqrt(H*H) + sqrt(H*H) + sqrt(H*H) + sqrt(H*H) to obtain H. Do this even if the value of b and the value of c are the same. As an example, consider the list 1, 4, 4. We then need to solve the equation:
sqrt(1*1) + sqrt(1*4) + sqrt(1*4) + sqrt(4*4) + sqrt(4*4) + sqrt(4*4) = sqrt(H*H) + sqrt(H*H) + sqrt(H*H) + sqrt(H*H) + sqrt(H*H) + sqrt(H*H). Its solution is H = 17/6.
All averages (including esoteric ones like the Heronian mean) can be thought of as examples of this general method for obtaining averages. A number of averages, including the ones discussed above, that have been found to be useful in some circumstance or other are listed below along with their formal solutions.
# Other averages
Other more sophisticated averages are: trimean, trimedian, and normalized mean. These are usually more representative of the whole data set.
One can create one's own average metric using generalized f-mean:
where f is any invertible function. The harmonic mean is an example of this using f(x) = 1/x, and the geometric mean is another, using f(x) = log x. Another example, expmean (exponential mean) is a mean using the function f(x) = ex, and it is inherently biased towards the higher values. However, this method for generating means is not general enough to capture all averages. The Heronian cannot be put into this form. A more general method for defining an average, y, takes any function of a list g(x1, x2, ..., xn), which is symmetric under permutation of the members of the list, and equates it to the same function with the value of the average replacing each member of the list: g(x1, x2, ..., xn) = g(y, y, ..., y). This most general definition still captures the important property of all averages that the average of a list of identical elements is that element itself.
The function g(x1, x2, ..., xn) =x1+x2+ ...+ xn provides the arithmetic mean.
The function g(x1, x2, ..., xn) =x1·x2· ...· xn provides the geometric mean.
The function g(x1, x2, ..., xn) =x1−1+x2−1+ ...+ xn−1 provides the harmonic mean.
# Average applied to a data stream
The concept of an average can be applied to a stream of data as well as a bounded set, the goal being to find a value about which recent data is in some way clustered. The stream may be distributed in time, as in samples taken by some data acquisition system from which we want to remove noise, or in space, as in pixels in an image from which we want to extract some property. An easy-to-understand and widely used application of average to a stream is the simple moving average in which we compute the arithmetic mean of the most recent N data items in the stream. To advance one position in the stream, we add 1/N times the new data item and subtract 1/N times the data item N places back in the stream.
# Derivation of the name
The original meaning of the word average is "damage sustained at sea": the same word is found in Arabic as awar, in Italian as avaria and in French as avarie. Hence an average adjuster is a person who assesses an insurable loss.
Marine damage is either particular average, which is borne only by the owner of the damaged property, or general average, where the owner can claim a proportional contribution from all the parties to the marine venture. The type of calculations used in adjusting general average gave rise to the use of "average" to mean "arithmetic mean". | Average
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
# Overview
In mathematics, an average, or central tendency of a data set refers to a measure of the "middle" or "expected" value of the data set. There are many different descriptive statistics that can be chosen as a measurement of the central tendency of the data items. The most common method is the arithmetic mean, but there are many other types of averages.
Colloquially, people often use the term average to refer to an intuitive central tendency without having a specific measurement of central tendency in mind, or use terms such as "the average person". However, the phrase "there's no such thing as an average citizen" emphasizes that the average is a number, not a person or some other object. The average is calculated by combining the measurements related to a group of people or objects, to compute a number as being the average of the group.
Please see the table of mathematical symbols for explanations of the symbols used. In statistics, the term central tendency is used in some fields of empirical research to refer to what statisticians sometimes call "location". A "measure of central tendency" is either a location parameter or a statistic used to estimate a location parameter.
# Calculating averages
An average is a representative value of a list. If all the numbers in the list were the same, then this number should be used. What if they are not the same? There are many different possible answers to this question. The average should not depend on the order of the numbers in the list, and it is often useful to also require that it should not be less than the smaller number in the list, nor greater than the greater number in the list (but see the annualiztion of of returns for other than one year in duration).
An easy way to get a representative value from a list is to randomly pick any number from the list. However, the word 'average' is usually reserved for more sophisticated methods that are generally found to be more useful.
The most common type of average is the arithmetic mean, often simply called the mean. The arithmetic mean of two numbers, such as 2 and 8, is obtained by finding a value A such that 2 + 8 = A + A. It is then simple to find that A = (2 + 8)/2 = 5. Switching the order of 2 and 8 to read 8 and 2 does not change the resulting value obtained for A. The mean 5 is not less than the minimum 2 nor greater than the maximum 8. If we increase the number of terms in the list for which we want an average, we get, for example, that the arithmetic mean of 2, 8, and 11 is found by solving for the value of A in the equation 2 + 8 + 11 = A + A + A. It is simple to find that A = (2 + 8 + 11)/3 = 7. Again we see that changing the order of the three members of the list does not change the result: A = (8 + 11 + 2)/3 = 7, and that 7 is between 2 and 11. This summation method is easily generalized for lists with any number of elements. It is also easy to see that the mean of a list of integers is not necessarily an integer. "The average family has 1.7 children" is an unpleasant way of expressing that the average number of children in some list of families is 1.7. The temperature represented by the arithmetic mean of a list of temperatures does not depend on whether the Fahrenheit or the Celcius scale is used, and this is one reason why an 'average temperature' is useful.
There are many other kinds of averages. However, they can all be understood in the same manner. For example, sometimes it is informative to consider the geometric mean. Here, instead of adding numbers we multiply them. Thus, the geometric mean of 2 and 8 is obtained by solving for G in the following equation: 2 * 8 = G * G. Thus, the geometric mean of 2 and 8 is G = sqrt(2 * 8) = 4. And again it is seen that changing the order of the members of the list to be averaged does not change the result: G = sqrt(8 * 2) = 4. In order to make sense of the requirement that the mean must be at least as big as the smallest member of the list and no bigger than the largest, the geometric mean is usually only applied to lists of positive numbers, not to lists that can include negative numbers such as temperatures.
It should now be obvious that it would be easy to come up with many other ways of combining the elements of a list in a manner that does not change when the order of the list is changed. For each of them one can define an average based on that method.
The most frequently occurring number in a list of numbers is called the mode. So the mode of the list (1, 2, 2, 3, 3, 3, 4) is 3. The mode is not necessarily well defined. The list (1, 2, 2, 3, 3, 5) has the two modes 2 and 3. The mode can be subsumed under the general method of defining averages by understanding it as taking the list and setting each member of the list equal to the most common value in the list if there is a most common value. This list is then equated to a the resulting list with all values replaced by the same value. Since they are already all the same, this does not require any change.
Another average worth discussing is the median. Its method is to order the list according to its magnitude and then repeatedly remove the pair consisting of the highest and lowest value till either one or two values are left. If two values are left replace them with their arithmetic mean. This method takes the list 1, 7, 3, 13 and orders it to read 1, 3, 7, 13. Then the 1 and 13 are removed to obtain the list 3, 7. Since there are two elements in this list replace them by their arithmetic mean (3 + 7)/2 = 5. Now do the same for the equal sized list consisting of all the same value M: M, M, M, M. It is already ordered. We remove the two end values to get M, M. We take their arithmetic mean to get M. Finally, set this result equal to our previous result to get M = 5.
In finance people are often interested in the annualized return which is a different kind of average. To begin with an example consider two years in which the return in the first year is minus 10% and the return in the second year is plus 60%. Then the annualized return, R, would be obtained by solving the equation: (1 - 10%) * (1 + 60%) = (1 + R) * (1 + R). The value of R that makes this equation true is R = 12%. It is again to be noted that changing the order to find the annualized return of 60% and -10% gives the same result as the annualized return of -10% and 60%. This method can be generalized to examples where the periods are not all of one-year duration. Annualization of a set of returns is a variation on the geometric average that provides the intensive property of a return per year corresponding to a list of returns. Consider a function that adds one to each return in the list and then takes the T th root of their product, where T is the sum of the periods of all the returns. This function is set equal to the same function for a list with the same number of elements composed of identical single year returns, whose value is the annualized return. For example, consider a period of a half of a year for which the return is minus 20% and a period of two and one half years for which the return is 116%. The annualized return for the combined period is the single year return, R, that is the solution of the following equation:
{(1-20%)*(1+116%)}^{1/(0.5 + 2.5)} = {(1+R)*(1+R)}^{1/(1 + 1)},
giving an annualized return, R, of 20%.
The Heronian mean H, is obtained by taking the sum of the square root of the product of each paired combination of two members of a list. Since the pairs are created by all ways of picking twice from the list while ignoring the order, the pair (a,c) is picked only once since (a,c) is the same as (c,a). However, the same element of the list can be picked twice within a single pair to get (a,a). Also, since it is the element on the list that is picked, not the value, if the same value appears twice on the list, different ways of picking it are included. Therefore, if the list has three members, designated a, b, c, then set sqrt(a*a) + sqrt(a*b) + sqrt(a*c) + sqrt(b*b) + sqrt(b*c) + sqrt(c*c) equal to sqrt(H*H) + sqrt(H*H) + sqrt(H*H) + sqrt(H*H) + sqrt(H*H) + sqrt(H*H) to obtain H. Do this even if the value of b and the value of c are the same. As an example, consider the list 1, 4, 4. We then need to solve the equation:
sqrt(1*1) + sqrt(1*4) + sqrt(1*4) + sqrt(4*4) + sqrt(4*4) + sqrt(4*4) = sqrt(H*H) + sqrt(H*H) + sqrt(H*H) + sqrt(H*H) + sqrt(H*H) + sqrt(H*H). Its solution is H = 17/6.
All averages (including esoteric ones like the Heronian mean) can be thought of as examples of this general method for obtaining averages. A number of averages, including the ones discussed above, that have been found to be useful in some circumstance or other are listed below along with their formal solutions.
# Other averages
Other more sophisticated averages are: trimean, trimedian, and normalized mean. These are usually more representative of the whole data set.
One can create one's own average metric using generalized f-mean:
where f is any invertible function. The harmonic mean is an example of this using f(x) = 1/x, and the geometric mean is another, using f(x) = log x. Another example, expmean (exponential mean) is a mean using the function f(x) = ex, and it is inherently biased towards the higher values. However, this method for generating means is not general enough to capture all averages. The Heronian cannot be put into this form. A more general method for defining an average, y, takes any function of a list g(x1, x2, ..., xn), which is symmetric under permutation of the members of the list, and equates it to the same function with the value of the average replacing each member of the list: g(x1, x2, ..., xn) = g(y, y, ..., y). This most general definition still captures the important property of all averages that the average of a list of identical elements is that element itself.
The function g(x1, x2, ..., xn) =x1+x2+ ...+ xn provides the arithmetic mean.
The function g(x1, x2, ..., xn) =x1·x2· ...· xn provides the geometric mean.
The function g(x1, x2, ..., xn) =x1−1+x2−1+ ...+ xn−1 provides the harmonic mean.
# Average applied to a data stream
The concept of an average can be applied to a stream of data as well as a bounded set, the goal being to find a value about which recent data is in some way clustered. The stream may be distributed in time, as in samples taken by some data acquisition system from which we want to remove noise, or in space, as in pixels in an image from which we want to extract some property. An easy-to-understand and widely used application of average to a stream is the simple moving average in which we compute the arithmetic mean of the most recent N data items in the stream. To advance one position in the stream, we add 1/N times the new data item and subtract 1/N times the data item N places back in the stream.
# Derivation of the name
The original meaning of the word average is "damage sustained at sea": the same word is found in Arabic as awar, in Italian as avaria and in French as avarie. Hence an average adjuster is a person who assesses an insurable loss.
Marine damage is either particular average, which is borne only by the owner of the damaged property, or general average, where the owner can claim a proportional contribution from all the parties to the marine venture. The type of calculations used in adjusting general average gave rise to the use of "average" to mean "arithmetic mean".
# External links
- Median as a weighted arithmetic mean of all Sample Observations
- Calculations and comparison between arithmetic and geometric mean of two values
Template:WikiDoc Sources | https://www.wikidoc.org/index.php/Average | |
bdf0d3e23dc9d4152b56abd0f7d42aaeef60b32e | wikidoc | Azulene | Azulene
Azulene is an organic compound whose molecules contain 10 carbons and 8 hydrogens and consist of a five-membered ring fused to a seven-membered ring. It is a monoterpene. It is an isomer of naphthalene but its physical properties are quite different. Naphthalene is a white crystalline solid whereas azulene, whose name is derived from the Spanish word azul, meaning "blue", is a dark blue crystalline solid used in many cosmetics. Azulene has a long history dating back to the 15th century as the azure-blue distillate obtained by steam distillation of Chamomile. The compound was discovered and named in 1863 by Septimus Piesse in azure-blue distillates from other sources such as yarrow and wormwood. Lavoslav Ružička solved the structure for this compound and the first organic synthesis followed in 1937 by Placidus Plattner.
# Derivatives
Vetivazulene or 4,8-dimethyl-2-isopropylazulene is obtained from vetiver oil. Guaiazulene or 1,4-dimethyl-7-isopropylazulene occurs naturally as a constituent of guaiac wood oil.
# Structure
Azulene consists of a fused cyclopentadiene ring and a cycloheptatriene ring and is an isomer of naphthalene. Azulene is 10 pi electron system just like cyclodecapentaene and does have aromatic properties even though it is not a single ring system like benzene. The peripheral bonds have similar lengths and only the shared bond in the middle is a single bond. The stability gain from aromaticity is half of that of naphthalene. The molecule can be considered a fusion product of a 6 pi electron cyclopentadienyl anion which is aromatic and the likewise aromatic 6 pi electron tropylium cation. The observed dipole moment of 1.0 Debye is consistent with this picture.
# Organic synthesis
For many years not many synthetic routes existed to azulene and the compound was therefore expensive. A recent contribution takes cycloheptatriene as starting material .
In naphthazulenes, a naphthalene ring is condensed with the 1,2-position of an azulene ring. In one such system deformation from planarity is found similar to that of tetrahelicene. | Azulene
Azulene is an organic compound whose molecules contain 10 carbons and 8 hydrogens and consist of a five-membered ring fused to a seven-membered ring. It is a monoterpene. It is an isomer of naphthalene but its physical properties are quite different. Naphthalene is a white crystalline solid whereas azulene, whose name is derived from the Spanish word azul, meaning "blue", is a dark blue crystalline solid used in many cosmetics. Azulene has a long history dating back to the 15th century as the azure-blue distillate obtained by steam distillation of Chamomile. The compound was discovered and named in 1863 by Septimus Piesse in azure-blue distillates from other sources such as yarrow and wormwood. Lavoslav Ružička solved the structure for this compound and the first organic synthesis followed in 1937 by Placidus Plattner.
# Derivatives
Vetivazulene or 4,8-dimethyl-2-isopropylazulene is obtained from vetiver oil. Guaiazulene or 1,4-dimethyl-7-isopropylazulene occurs naturally as a constituent of guaiac wood oil.
# Structure
Azulene consists of a fused cyclopentadiene ring and a cycloheptatriene ring and is an isomer of naphthalene. Azulene is 10 pi electron system just like cyclodecapentaene and does have aromatic properties even though it is not a single ring system like benzene. The peripheral bonds have similar lengths and only the shared bond in the middle is a single bond. The stability gain from aromaticity is half of that of naphthalene. The molecule can be considered a fusion product of a 6 pi electron cyclopentadienyl anion which is aromatic and the likewise aromatic 6 pi electron tropylium cation. The observed dipole moment of 1.0 Debye is consistent with this picture.
# Organic synthesis
For many years not many synthetic routes existed to azulene and the compound was therefore expensive. A recent contribution takes cycloheptatriene as starting material [1].
In naphth[a]azulenes, a naphthalene ring is condensed with the 1,2-position of an azulene ring. In one such system [2] deformation from planarity is found similar to that of tetrahelicene.
# External links
- MSDS Website
- MSDS Website | https://www.wikidoc.org/index.php/Azulene | |
a36c6bbe682bc22b23feb62433554144f9aa4646 | wikidoc | Azurite | Azurite
Azurite is a soft, deep blue copper mineral produced by weathering of copper ore deposits. It is also known as Chessylite after the Chessy-les-Mines near Lyon, France, where striking specimens have been found. The mineral has been known since ancient times, and was mentioned in Pliny the Elder's Natural History under the Greek name kuanos ("deep blue," root of English cyan) and the Latin name caeruleum The blue of azurite is exceptionally deep and clear, and for that reason the mineral has tended to be associated since antiquity with the deep blue color of low-humidity desert and winter skies. The modern English name of the mineral reflects this association, since both azurite and azure are derived via Arabic from the Persian lazhward, an area known for its deposits of another deep blue stone, lapis lazuli ("stone of azure").
# Mineralogy
Azurite crystals are monoclinic, and when large enough to be seen they appear as dark blue prismatic crystals. Azurite specimens are typically massive to nodular, and are often stalactitic in form. Specimens tend to lighten in color over time due to weathering of the specimen surface into malachite. Azurite is soft, with a Mohs hardness of only 3.5 to 4. The specific gravity of azurite is 3.77 to 3.89. Azurite is destroyed by heat, losing carbon dioxide and water to form black, powdery copper(II) oxide. Characteristic of a carbonate, specimens effervece upon treatment with hydrochloric acid.
# Uses
## Pigments
Azurite was used as a blue pigment for centuries. It was formerly known as Azurro Della Magna (from Italian). When mixed with oil it turns slightly green. When mixed with egg yolk it turns green-grey. It is also known by the names Blue Bice and Blue Verditer. Older examples of azurite pigment may show a more greenish tint due to weathering into malachite.
Azurite was distinguished from (the much more expensive) purified natural ultramarine blue by heating (as described by Cennino D'Andrea Cennini). Ultramarine withstands heat, whereas azurite turns black (copper oxide). Gentle heating of azurite produces a deep blue pigment used in Japanese painting techniques.
## Jewelry
Azurite is used occasionally as beads and as jewelry, and also as an ornamental stone. However, its softness and tendency to lose its deep blue color as it weathers limit such uses. Heating destroys azurite easily, so all mounting of azurite specimens must be done at room temperature. When tumbled, azurite takes a fine polish, showing a dazzling display of shades of blue and violet.
## Collecting
The intense color of azurite makes it popular collector's stone. However, bright light, heat, and open air all tend to reduce the intensity of its color over time. To help preserve the deep blue color of a pristine azurite specimen, collectors should use a cool, dark, sealed storage environment similar to that of its original natural setting.
## Prospecting
While not a major ore of copper itself, azurite is a good surface indicator of the presence of weathered copper sulfide ores. It is usually found in association with the chemically very similar malachite, producing a striking color combination of deep blue and bright green that is strongly indicative of the presence of copper ores.
# History
The use of azurite and malachite as copper ore indicators led indirectly to the name of the element nickel in the English language. Nickeline, a principal ore of nickel that is also known as niccolite, weathers at the surface into a green mineral (annabergite) that resembles malachite. This resemblance resulted in occasional attempts to smelt nickeline in the belief that it was copper ore, but such attempts always ended in failure due to high smelting temperatures needed to reduce nickel. In Germany this deceptive mineral came to be known as kupfernickel, literally "copper demon". The Swedish alchemist Baron Axel Fredrik Cronstedt (who had been trained by Georg Brandt, the discoverer of the nickel-like metal cobalt) realized that there was probably a new metal hiding within the kupfernickel ore, and in 1751 he succeeded in smelting kupfernickel to produce a previously unknown (except in certain meteorites) silvery white, iron-like metal. Logically, Cronstedt named his new metal after the nickel part of kupfernickel. An unintended later consequence of his choice is that both Canadian and American coins worth one-twentieth of a dollar are now named after the German word for "demons"—that is, they are called nickels.
# Composition
Azurite is one of two basic copper(II) carbonate minerals, the other being bright green malachite. Simple copper carbonate (CuCO3) is not known to exist in nature. In azurite, copper(II) is linked to two different anions, carbonate and hydroxide, the compound has the formula Cu3(CO3)2(OH)2. The optical properties (color, intensity) of minerals such as azurite and malachite are explained in the context of conventional electronic spectroscopy of coordination complexes. Relatively detailed description are provided by Ligand Field Theory. Blue-colored species akin to the azurite can be obtained by combining solutions of copper sulfate with a saturated solution of sodium carbonate.
## Weathering
Azurite is unstable in open air with respect to malachite, and often is pseudomorphically replaced by malachite. The weathering process effect of the replacement of some the carbon dioxide (CO2) units with water (H2O). This change in the carbonate/hydroxide ratio of azurite into the 1-to-1 ratio of malachite:
From the above equation the conversion of azurite into malachite is attributable to the low partial pressure of carbon dioxide in air. Azurite is also incompatible with aquatic media, such as salt-water aquariums.
## Toxicity
Minerals in general should not be ingested.
## Gallery
- File:Azurite-velvet-beauty.jpg
- File:Azurite-pyramidal-copper-3D-balls.png
- File:Trans-Cu-complex-in-azurite-3D-balls.png | Azurite
Template:Infobox mineral
Azurite is a soft, deep blue copper mineral produced by weathering of copper ore deposits. It is also known as Chessylite after the Chessy-les-Mines[1] near Lyon, France, where striking specimens have been found. The mineral has been known since ancient times, and was mentioned in Pliny the Elder's Natural History under the Greek name kuanos ("deep blue," root of English cyan) and the Latin name caeruleum[2] The blue of azurite is exceptionally deep and clear, and for that reason the mineral has tended to be associated since antiquity with the deep blue color of low-humidity desert and winter skies. The modern English name of the mineral reflects this association, since both azurite and azure are derived via Arabic from the Persian lazhward, an area known for its deposits of another deep blue stone, lapis lazuli ("stone of azure").
# Mineralogy
Azurite[3][4][5] crystals are monoclinic, and when large enough to be seen they appear as dark blue prismatic crystals. Azurite specimens are typically massive to nodular, and are often stalactitic in form. Specimens tend to lighten in color over time due to weathering of the specimen surface into malachite. Azurite is soft, with a Mohs hardness of only 3.5 to 4. The specific gravity of azurite is 3.77 to 3.89. Azurite is destroyed by heat, losing carbon dioxide and water to form black, powdery copper(II) oxide. Characteristic of a carbonate, specimens effervece upon treatment with hydrochloric acid.
# Uses
## Pigments
Azurite was used as a blue pigment for centuries. It was formerly known as Azurro Della Magna (from Italian). When mixed with oil it turns slightly green. When mixed with egg yolk it turns green-grey. It is also known by the names Blue Bice and Blue Verditer. Older examples of azurite pigment may show a more greenish tint due to weathering into malachite.
Azurite was distinguished from (the much more expensive) purified natural ultramarine blue by heating (as described by Cennino D'Andrea Cennini). Ultramarine withstands heat, whereas azurite turns black (copper oxide). Gentle heating of azurite produces a deep blue pigment used in Japanese painting techniques.
## Jewelry
Azurite is used occasionally as beads and as jewelry, and also as an ornamental stone. However, its softness and tendency to lose its deep blue color as it weathers limit such uses. Heating destroys azurite easily, so all mounting of azurite specimens must be done at room temperature. When tumbled, azurite takes a fine polish, showing a dazzling display of shades of blue and violet.
## Collecting
The intense color of azurite makes it popular collector's stone. However, bright light, heat, and open air all tend to reduce the intensity of its color over time. To help preserve the deep blue color of a pristine azurite specimen, collectors should use a cool, dark, sealed storage environment similar to that of its original natural setting.
## Prospecting
While not a major ore of copper itself, azurite is a good surface indicator of the presence of weathered copper sulfide ores. It is usually found in association with the chemically very similar malachite, producing a striking color combination of deep blue and bright green that is strongly indicative of the presence of copper ores.
# History
The use of azurite and malachite as copper ore indicators led indirectly to the name of the element nickel in the English language. Nickeline, a principal ore of nickel that is also known as niccolite, weathers at the surface into a green mineral (annabergite) that resembles malachite. This resemblance resulted in occasional attempts to smelt nickeline in the belief that it was copper ore, but such attempts always ended in failure due to high smelting temperatures needed to reduce nickel. In Germany this deceptive mineral came to be known as kupfernickel, literally "copper demon". The Swedish alchemist Baron Axel Fredrik Cronstedt (who had been trained by Georg Brandt, the discoverer of the nickel-like metal cobalt) realized that there was probably a new metal hiding within the kupfernickel ore, and in 1751 he succeeded in smelting kupfernickel to produce a previously unknown (except in certain meteorites) silvery white, iron-like metal. Logically, Cronstedt named his new metal after the nickel part of kupfernickel. An unintended later consequence of his choice is that both Canadian and American coins worth one-twentieth of a dollar are now named after the German word for "demons"—that is, they are called nickels.
# Composition
Azurite is one of two basic copper(II) carbonate minerals, the other being bright green malachite. Simple copper carbonate (CuCO3) is not known to exist in nature. In azurite, copper(II) is linked to two different anions, carbonate and hydroxide, the compound has the formula Cu3(CO3)2(OH)2. The optical properties (color, intensity) of minerals such as azurite and malachite are explained in the context of conventional electronic spectroscopy of coordination complexes. Relatively detailed description are provided by Ligand Field Theory. Blue-colored species akin to the azurite can be obtained by combining solutions of copper sulfate with a saturated solution of sodium carbonate.
## Weathering
Azurite is unstable in open air with respect to malachite, and often is pseudomorphically replaced by malachite. The weathering process effect of the replacement of some the carbon dioxide (CO2) units with water (H2O). This change in the carbonate/hydroxide ratio of azurite into the 1-to-1 ratio of malachite:
From the above equation the conversion of azurite into malachite is attributable to the low partial pressure of carbon dioxide in air. Azurite is also incompatible with aquatic media, such as salt-water aquariums.
## Toxicity
Minerals in general should not be ingested.
## Gallery
- File:Azurite-velvet-beauty.jpg
- File:Azurite-pyramidal-copper-3D-balls.png
- File:Trans-Cu-complex-in-azurite-3D-balls.png | https://www.wikidoc.org/index.php/Azurite | |
a4ee2e616a4d1d6926ffd765d011726fa8acd88c | wikidoc | B4GALT7 | B4GALT7
Beta-1,4-galactosyltransferase 7 also known as galactosyltransferase I is an enzyme that in humans is encoded by the B4GALT7 gene. Galactosyltransferase I catalyzes the synthesis of the glycosaminoglycan-protein linkage in proteoglycans. Proteoglycans in turn are structural components of the extracellular matrix that is found between cells in connective tissues.
# Function
Galactosyltransferase I is one of seven β-1,4-galactosyltransferase (β4GalT) enzymes. These enzymes are type II membrane-bound glycoproteins that appear to have exclusive specificity for the donor substrate UDP-galactose; all transfer galactose in a β-1,4 linkage to similar acceptor sugars: GlcNAc, Glc, and Xyl. Each beta4GalT has a distinct function in the biosynthesis of different glycoconjugates and saccharide structures. As type II membrane proteins, they have an N-terminal hydrophobic signal sequence that directs the protein to the Golgi apparatus and which then remains uncleaved to function as a transmembrane anchor. By sequence similarity, the beta4GalTs form four groups: β4GalT1 and β4GalT2, β4GalT3 and β4GalT4, β4GalT5 and β4GalT6, and β4GalT7. The enzyme encoded by this gene attaches the first galactose in the common carbohydrate-protein (GlcA-β-1,3-Gal-β-1,3-Gal-β-1,4-Xyl-beta1-O-Ser) linkage found in proteoglycans. Manganese is required as a cofactor. This enzyme differs from the other six beta4GalTs because it lacks the conserved β4GalT1-β4GalT6 Cys residues and it is located in cis-Golgi instead of trans-Golgi.
# Clinical significance
Mutations in the B4GALT7 gene that result in a defective galactosyltransferase I enzyme with reduced or absent activity are associated with progeroid type Ehlers-Danlos syndrome. Since mutations in B4GALT7 impair a glycosylation pathway, the resulting subtype of Ehlers-Danlos syndrome may be considered a congenital disorder of glycosylation (CDG), according to the new CDG nomenclature.
Mutations in B4GALT7 cause Larsen syndrome .Cartault, F; Munier, P; Jacquemont, M. L.; Vellayoudom, J; Doray, B; Payet, C; Randrianaivo, H; Laville, J. M.; Munnich, A; Cormier-Daire, V (2014). "Expanding the clinical spectrum of B4GALT7 deficiency: Homozygous p.R270C mutation with founder effect causes Larsen of Reunion Island syndrome". European Journal of Human Genetics. 23: 49–53. doi:10.1038/ejhg.2014.60. PMC 4266744. PMID 24755949..mw-parser-output cite.citation{font-style:inherit}.mw-parser-output q{quotes:"\"""\"""'""'"}.mw-parser-output code.cs1-code{color:inherit;background:inherit;border:inherit;padding:inherit}.mw-parser-output .cs1-lock-free a{background:url("")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-limited a,.mw-parser-output .cs1-lock-registration a{background:url("")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-subscription a{background:url("")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration{color:#555}.mw-parser-output .cs1-subscription span,.mw-parser-output .cs1-registration span{border-bottom:1px dotted;cursor:help}.mw-parser-output .cs1-hidden-error{display:none;font-size:100%}.mw-parser-output .cs1-visible-error{display:none;font-size:100%}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration,.mw-parser-output .cs1-format{font-size:95%}.mw-parser-output .cs1-kern-left,.mw-parser-output .cs1-kern-wl-left{padding-left:0.2em}.mw-parser-output .cs1-kern-right,.mw-parser-output .cs1-kern-wl-right{padding-right:0.2em} | B4GALT7
Beta-1,4-galactosyltransferase 7 also known as galactosyltransferase I is an enzyme that in humans is encoded by the B4GALT7 gene.[1][1][2][2][3] Galactosyltransferase I catalyzes the synthesis of the glycosaminoglycan-protein linkage in proteoglycans.[4] Proteoglycans in turn are structural components of the extracellular matrix that is found between cells in connective tissues.
# Function
Galactosyltransferase I is one of seven β-1,4-galactosyltransferase (β4GalT) enzymes. These enzymes are type II membrane-bound glycoproteins that appear to have exclusive specificity for the donor substrate UDP-galactose; all transfer galactose in a β-1,4 linkage to similar acceptor sugars: GlcNAc, Glc, and Xyl. Each beta4GalT has a distinct function in the biosynthesis of different glycoconjugates and saccharide structures. As type II membrane proteins, they have an N-terminal hydrophobic signal sequence that directs the protein to the Golgi apparatus and which then remains uncleaved to function as a transmembrane anchor. By sequence similarity, the beta4GalTs form four groups: β4GalT1 and β4GalT2, β4GalT3 and β4GalT4, β4GalT5 and β4GalT6, and β4GalT7. The enzyme encoded by this gene attaches the first galactose in the common carbohydrate-protein (GlcA-β-1,3-Gal-β-1,3-Gal-β-1,4-Xyl-beta1-O-Ser) linkage found in proteoglycans. Manganese is required as a cofactor. This enzyme differs from the other six beta4GalTs because it lacks the conserved β4GalT1-β4GalT6 Cys residues and it is located in cis-Golgi instead of trans-Golgi.[3]
# Clinical significance
Mutations in the B4GALT7 gene that result in a defective galactosyltransferase I enzyme with reduced or absent activity are associated with progeroid type Ehlers-Danlos syndrome.[2][4][5][6] Since mutations in B4GALT7 impair a glycosylation pathway, the resulting subtype of Ehlers-Danlos syndrome may be considered a congenital disorder of glycosylation (CDG), according to the new CDG nomenclature.
Mutations in B4GALT7 cause Larsen syndrome .Cartault, F; Munier, P; Jacquemont, M. L.; Vellayoudom, J; Doray, B; Payet, C; Randrianaivo, H; Laville, J. M.; Munnich, A; Cormier-Daire, V (2014). "Expanding the clinical spectrum of B4GALT7 deficiency: Homozygous p.R270C mutation with founder effect causes Larsen of Reunion Island syndrome". European Journal of Human Genetics. 23: 49–53. doi:10.1038/ejhg.2014.60. PMC 4266744. PMID 24755949..mw-parser-output cite.citation{font-style:inherit}.mw-parser-output q{quotes:"\"""\"""'""'"}.mw-parser-output code.cs1-code{color:inherit;background:inherit;border:inherit;padding:inherit}.mw-parser-output .cs1-lock-free a{background:url("https://upload.wikimedia.org/wikipedia/commons/thumb/6/65/Lock-green.svg/9px-Lock-green.svg.png")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-limited a,.mw-parser-output .cs1-lock-registration a{background:url("https://upload.wikimedia.org/wikipedia/commons/thumb/d/d6/Lock-gray-alt-2.svg/9px-Lock-gray-alt-2.svg.png")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-subscription a{background:url("https://upload.wikimedia.org/wikipedia/commons/thumb/a/aa/Lock-red-alt-2.svg/9px-Lock-red-alt-2.svg.png")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration{color:#555}.mw-parser-output .cs1-subscription span,.mw-parser-output .cs1-registration span{border-bottom:1px dotted;cursor:help}.mw-parser-output .cs1-hidden-error{display:none;font-size:100%}.mw-parser-output .cs1-visible-error{display:none;font-size:100%}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration,.mw-parser-output .cs1-format{font-size:95%}.mw-parser-output .cs1-kern-left,.mw-parser-output .cs1-kern-wl-left{padding-left:0.2em}.mw-parser-output .cs1-kern-right,.mw-parser-output .cs1-kern-wl-right{padding-right:0.2em} | https://www.wikidoc.org/index.php/B4GALT7 | |
f2f57bc1d058ebc4fb028a2b438429651ad6d4e1 | wikidoc | BBR3464 | BBR3464
# Overview
BBR3464 (rINN: triplatin tetranitrate) is a new platinum-based cytotoxic drug that is currently undergoing clinical trials throughout the world for the treatment of human cancer. It is a trinuclear platinum coordination complex, with chloride and amine ligands. The drug acts by forming coordinate covalent adducts with cellular DNA, preventing DNA transcription and replication, and through this inducing apoptosis. BBR3464 is structurally similar to, but in a different family from, the anticancer drugs cisplatin, carboplatin and oxaliplatin.
# History
BBR3464 was invented by Professor Nicholas Farrell at Virginia Commonwealth University in the United States. The development of this drug came from his earlier work looking at dinuclear platinum derivatives of cisplatin, research he began in the late 1980s. Similar work was also being undertaken by Dr John Broomhead at the Australian National University in Australia. BBR3464 was patented in the mid-1990s and was originally licensed to the pharmaceutical company Roche. In preclinical trials, BBR3464 demonstrated cytotoxic activity in cancer cell lines which have either intrinsic or acquired resistance to cisplatin. On this basis it entered Phase I (Toxicity) clinical trials under the auspices of Novuspharma before the rights were transferred to Cell Therapeutics.
This drug is currently undergoing Phase II (Efficacy) trials with mixed results. So far trials of the drug with patients suffering from ovarian cancer, small cell lung cancer and gastric or gastro-oesophageal adenocarcinomas have been reported in the literature.
# Mode of action
The main target of BBR3464 is cellular DNA, similar to cisplatin. Outside of the cell, the concentration of chloride (approx. 100 millimolar) prevents the drugs from hydrolysing, but once inside the cell, where the concentration of chloride drops to between 4 and 20 millimolar, the chloride ligands of BBR3464 come off and the drug is capable of forming coordinate covalent bonds with purine bases on DNA. The novel adducts BBR3464 forms with DNA are though to be the mechanism by which this drug acts; the adducts are able to prevent DNA transcription and replication, thus inducing cell apoptosis.
# Side-effects
All platinum based drugs, and particularly BBR3464, cause large dose limiting side-effects. For BBR3464 these are largely diarrhoea, cramps and vomiting, but are so severe that the maximum tolerated dose (MTD) in humans is between 0.9 to 1.1 milligrams per square metre. This is considerably lower than the MTD for all the platinum based drugs currently used in the clinic, like cisplatin (60–120 mg) and carboplatin (approx. 800 mg). | BBR3464
# Overview
BBR3464 (rINN: triplatin tetranitrate) is a new platinum-based cytotoxic drug that is currently undergoing clinical trials throughout the world for the treatment of human cancer. It is a trinuclear platinum coordination complex, with chloride and amine ligands. The drug acts by forming coordinate covalent adducts with cellular DNA, preventing DNA transcription and replication, and through this inducing apoptosis. BBR3464 is structurally similar to, but in a different family from, the anticancer drugs cisplatin, carboplatin and oxaliplatin.
# History
BBR3464 was invented by Professor Nicholas Farrell at Virginia Commonwealth University in the United States. The development of this drug came from his earlier work looking at dinuclear platinum derivatives of cisplatin, research he began in the late 1980s. Similar work was also being undertaken by Dr John Broomhead at the Australian National University in Australia. BBR3464 was patented in the mid-1990s and was originally licensed to the pharmaceutical company Roche. In preclinical trials, BBR3464 demonstrated cytotoxic activity in cancer cell lines which have either intrinsic or acquired resistance to cisplatin. On this basis it entered Phase I (Toxicity) clinical trials under the auspices of Novuspharma before the rights were transferred to Cell Therapeutics.
This drug is currently undergoing Phase II (Efficacy) trials with mixed results. So far trials of the drug with patients suffering from ovarian cancer, small cell lung cancer and gastric or gastro-oesophageal adenocarcinomas have been reported in the literature.
# Mode of action
The main target of BBR3464 is cellular DNA, similar to cisplatin. Outside of the cell, the concentration of chloride (approx. 100 millimolar) prevents the drugs from hydrolysing, but once inside the cell, where the concentration of chloride drops to between 4 and 20 millimolar, the chloride ligands of BBR3464 come off and the drug is capable of forming coordinate covalent bonds with purine bases on DNA. The novel adducts BBR3464 forms with DNA are though to be the mechanism by which this drug acts; the adducts are able to prevent DNA transcription and replication, thus inducing cell apoptosis.
# Side-effects
All platinum based drugs, and particularly BBR3464, cause large dose limiting side-effects. For BBR3464 these are largely diarrhoea, cramps and vomiting, but are so severe that the maximum tolerated dose (MTD) in humans is between 0.9 to 1.1 milligrams per square metre. This is considerably lower than the MTD for all the platinum based drugs currently used in the clinic, like cisplatin (60–120 mg) and carboplatin (approx. 800 mg). | https://www.wikidoc.org/index.php/BBR3464 | |
8beae85f9903624390cdd99c4e4e2d4750cc4cf5 | wikidoc | BCL2L11 | BCL2L11
Bcl-2-like protein 11, commonly called BIM, is a protein that in humans is encoded by the BCL2L11 gene.
# Function
The protein encoded by this gene belongs to the BCL-2 protein family. BCL-2 family members form hetero- or homodimers and act as anti- or pro-apoptotic regulators that are involved in a wide variety of cellular activities. The protein encoded by this gene contains a Bcl-2 homology domain 3 (BH3). It has been shown to interact with other members of the BCL-2 protein family, including BCL2, BCL2L1/BCL-X(L), and MCL1, and to act as an apoptotic activator. The expression of this gene can be induced by nerve growth factor (NGF), as well as by the forkhead transcription factor FKHR-L1 (FoxO3a), which suggests a role of this gene in neuronal and lymphocyte apoptosis. Transgenic studies of the mouse counterpart suggested that this gene functions as an essential initiator of apoptosis in thymocyte-negative selection. Several alternatively spliced transcript variants of this gene have been identified.
## Regulation of Bim
Bim expression and activity are regulated at the transcriptional, translational and post-translational levels; coordinated expression and activity of Bim shape immune responses, and ensure tissue integrity. Cancer cells develop mechanisms that suppress Bim expression, which allows for tumor progression and metastasis.
# Interactions
BCL2L11 has been shown to interact with:
- BCL2-like 1,
- BCL2L2,
- Bcl-2,
- DYNLL1, and
- MCL1. | BCL2L11
Bcl-2-like protein 11, commonly called BIM, is a protein that in humans is encoded by the BCL2L11 gene.[1][2]
# Function
The protein encoded by this gene belongs to the BCL-2 protein family. BCL-2 family members form hetero- or homodimers and act as anti- or pro-apoptotic regulators that are involved in a wide variety of cellular activities. The protein encoded by this gene contains a Bcl-2 homology domain 3 (BH3). It has been shown to interact with other members of the BCL-2 protein family, including BCL2, BCL2L1/BCL-X(L), and MCL1, and to act as an apoptotic activator. The expression of this gene can be induced by nerve growth factor (NGF), as well as by the forkhead transcription factor FKHR-L1 (FoxO3a), which suggests a role of this gene in neuronal and lymphocyte apoptosis. Transgenic studies of the mouse counterpart suggested that this gene functions as an essential initiator of apoptosis in thymocyte-negative selection. Several alternatively spliced transcript variants of this gene have been identified.[3]
## Regulation of Bim
Bim expression and activity are regulated at the transcriptional, translational and post-translational levels; coordinated expression and activity of Bim shape immune responses, and ensure tissue integrity. Cancer cells develop mechanisms that suppress Bim expression, which allows for tumor progression and metastasis.[4]
# Interactions
BCL2L11 has been shown to interact with:
- BCL2-like 1,[1][2][5][6]
- BCL2L2,[1][2]
- Bcl-2,[1][2][5]
- DYNLL1,[7][8] and
- MCL1.[1][5][9] | https://www.wikidoc.org/index.php/BCL2L11 | |
796d46f25dbc54ae352380a9bf7eaabe630e3d3d | wikidoc | BCL2L12 | BCL2L12
Bcl-2-like protein 12 is a protein that in humans is encoded by the BCL2L12 gene.
The protein encoded by this gene belongs to the Bcl-2 protein family. Bcl-2 family members form hetero- or homodimers and act as anti- or pro-apoptotic regulators that are involved in a wide variety of cellular activities. This protein contains a Bcl-2 homology domain 2 (BH2). The function of this gene has not yet been determined. Two alternatively spliced transcript variants of this gene encoding distinct isoforms have been reported.
Bcl2L12 expression is upregulated in most human glioblastomas. Expression of Bcl2L12 results in resistance to apoptosis. Bcl2L12 directly neutralizes caspase-7 (CASP7) and indirectly neutralizes caspase-3 (CASP3) by an indirect mechanism. Both caspase enzymes are known to play essential roles in the execution phase of apoptosis. | BCL2L12
Bcl-2-like protein 12 is a protein that in humans is encoded by the BCL2L12 gene.[1][2]
The protein encoded by this gene belongs to the Bcl-2 protein family. Bcl-2 family members form hetero- or homodimers and act as anti- or pro-apoptotic regulators that are involved in a wide variety of cellular activities. This protein contains a Bcl-2 homology domain 2 (BH2). The function of this gene has not yet been determined. Two alternatively spliced transcript variants of this gene encoding distinct isoforms have been reported.[1]
Bcl2L12 expression is upregulated in most human glioblastomas. Expression of Bcl2L12 results in resistance to apoptosis. Bcl2L12 directly neutralizes caspase-7 (CASP7) and indirectly neutralizes caspase-3 (CASP3) by an indirect mechanism.[3] Both caspase enzymes are known to play essential roles in the execution phase of apoptosis.[4] | https://www.wikidoc.org/index.php/BCL2L12 | |
d082025ab83f1212d3a798e7d88c43e85e60eeac | wikidoc | BCL2L13 | BCL2L13
BCL2-like 13 (apoptosis facilitator), also known as BCL2L13 or Bcl-rambo, is a protein which in humans is encoded by the BCL2L13 gene on chromosome 22. This gene encodes a mitochondrially-localized protein which is classified under the Bcl-2 protein family. Overexpression of the encoded protein results in apoptosis. As a result, it has been implicated in cancers such as childhood acute lymphoblastic leukemia (ALL) and glioblastoma multiforme (GBM). Alternatively spliced transcript variants have been observed for this gene, such as Bcl-rambo beta.
# Structure
As a member of the Bcl-2 protein family, Bcl-rambo comprises four conserved BH domains and a transmembrane (TM) domain. However, unlike the other members, Bcl-rambo does not require the BH domains for its apoptotic function, relying instead on the mitochondrial localization carried out by the TM domain. In addition to these domains, it has conserved B-cell lymphoma 2 homology motifs, as well as an extension at its c-terminal, termed the BHNo domain, which contains two tandem repeats, RTA and RTB.
An alternatively-spliced protein variant, called Bcl-rambo beta, is composed of only the BH4 domain, completely lacking the BH domains 1 through 3 due to an in-frame stop codon inserted by an Alu element. Without the TM domain, this variant remains in the cytosol and does not localize to the mitochondria. Nonetheless, it still performs proapoptotic activity, mediated by the encoded Alu element, though the exact mechanisms remain to be elucidated.
# Function
Bcl-rambo is a member of the Bcl-2 family of proteins that regulate apoptosis. In cells, Bcl-rambo is localized to the mitochondria, and its overexpression induces apoptosis that is blocked by caspase inhibitors, whereas inhibitors controlling upstream events of either the 'death receptor' (FLIP, FADD-DN) or the 'mitochondrial' pro-apoptotic pathway (Bcl-x(L)) had no effect. Bcl-rambo mediates apoptosis by associating with adenine nucleotide translocator (ANT), a component of the mitochondrial permeability transition pore, to induce its opening. ANT will also facilitate the transfer of ADP and ATP between the cytosol and the matrix.
# Clinical significance
The BCL2L13 gene has been implicated in a wide spectrum of cancers. Previous clinical studies observed in ALL patients that high expression of BCL2L13 correlated to lower event-free and overall survival. Though statistically significant, the observations contradict the accepted pro-apoptotic function of BCL2L13’s gene product, which should have contributed to cancer cell death and, thus, more favorable survival outcomes. Two possible explanations propose that either 1) Bcl-rambo performs a different biological role in childhood, or 2) alternative splicing could have generated an anti-apoptotic variant. More research is necessary to resolve this discrepancy. In another type of cancer, GBM, Bcl-rambo is known to inhibit induced apoptosis in GBM cells by binding two other pro-apoptotic proteins, ceramide synthases 2 (CerS2) and 6 (CerS6), thereby blocking CerS2/6 complex formation and activity. Thus, inhibiting BCL2L13 during cancer treatments may improve survival outcomes.
# Interactions
BCL2L13 has been shown to interact with:
- CerS2 and
- CerS6. | BCL2L13
BCL2-like 13 (apoptosis facilitator), also known as BCL2L13 or Bcl-rambo, is a protein which in humans is encoded by the BCL2L13 gene on chromosome 22. This gene encodes a mitochondrially-localized protein which is classified under the Bcl-2 protein family. Overexpression of the encoded protein results in apoptosis.[1][2] As a result, it has been implicated in cancers such as childhood acute lymphoblastic leukemia (ALL) and glioblastoma multiforme (GBM).[3][4] Alternatively spliced transcript variants have been observed for this gene, such as Bcl-rambo beta.[1][5]
# Structure
As a member of the Bcl-2 protein family, Bcl-rambo comprises four conserved BH domains and a transmembrane (TM) domain. However, unlike the other members, Bcl-rambo does not require the BH domains for its apoptotic function, relying instead on the mitochondrial localization carried out by the TM domain. In addition to these domains, it has conserved B-cell lymphoma 2 homology motifs, as well as an extension at its c-terminal, termed the BHNo domain, which contains two tandem repeats, RTA and RTB.[1][5]
An alternatively-spliced protein variant, called Bcl-rambo beta, is composed of only the BH4 domain, completely lacking the BH domains 1 through 3 due to an in-frame stop codon inserted by an Alu element. Without the TM domain, this variant remains in the cytosol and does not localize to the mitochondria. Nonetheless, it still performs proapoptotic activity, mediated by the encoded Alu element, though the exact mechanisms remain to be elucidated.[6]
# Function
Bcl-rambo is a member of the Bcl-2 family of proteins that regulate apoptosis. In cells, Bcl-rambo is localized to the mitochondria, and its overexpression induces apoptosis that is blocked by caspase inhibitors, whereas inhibitors controlling upstream events of either the 'death receptor' (FLIP, FADD-DN) or the 'mitochondrial' pro-apoptotic pathway (Bcl-x(L)) had no effect.[2] Bcl-rambo mediates apoptosis by associating with adenine nucleotide translocator (ANT), a component of the mitochondrial permeability transition pore, to induce its opening. ANT will also facilitate the transfer of ADP and ATP between the cytosol and the matrix.[5]
# Clinical significance
The BCL2L13 gene has been implicated in a wide spectrum of cancers. Previous clinical studies observed in ALL patients that high expression of BCL2L13 correlated to lower event-free and overall survival. Though statistically significant, the observations contradict the accepted pro-apoptotic function of BCL2L13’s gene product, which should have contributed to cancer cell death and, thus, more favorable survival outcomes. Two possible explanations propose that either 1) Bcl-rambo performs a different biological role in childhood, or 2) alternative splicing could have generated an anti-apoptotic variant. More research is necessary to resolve this discrepancy.[3] In another type of cancer, GBM, Bcl-rambo is known to inhibit induced apoptosis in GBM cells by binding two other pro-apoptotic proteins, ceramide synthases 2 (CerS2) and 6 (CerS6), thereby blocking CerS2/6 complex formation and activity. Thus, inhibiting BCL2L13 during cancer treatments may improve survival outcomes.[4]
# Interactions
BCL2L13 has been shown to interact with:
- CerS2[4] and
- CerS6.[4] | https://www.wikidoc.org/index.php/BCL2L13 | |
94b6d84fdf53b1afeca24801385a7d719007e89a | wikidoc | BHLHE41 | BHLHE41
"Basic helix-loop-helix family, member e41", or BHLHE41, is a gene that encodes a basic helix-loop-helix transcription factor repressor protein in various tissues of both humans and mice. It is also known as DEC2, hDEC2, and SHARP1, and was previously known as "basic helix-loop-helix domain containing, class B, 3", or BHLHB3. BHLHE41 is known for its role in the circadian molecular mechanisms that influence sleep quantity as well as its role in immune function and the maturation of T helper type 2 cell lineages associated with humoral immunity.
# History
Dr. Klaus-Armin Nave's lab identified BHLHE41/SHARP1 and BHLHE40/SHARP2 as a novel subfamily in the basic helix-loop-helix (BHLH) protein family. They differentiated BHLHE41/SHARP1 and BHLHE/40SHARP2 from other BHLH-protein encoding genes since they are not transcribed until the end of embryonic development. The DNA sequence of BHLHE41 was first obtained by Dr. Yukia Kato's lab through a cDNA library search. Particularly, they obtained the sequence of BHLHE40/DEC1 and conducted an expressed sequence tag (EST) search to identify the BHLHE41/DEC2 sequence. BHLHE41/DEC2 and BHLHE40/DEC1 share 97% homology in the BHLH domain. After the identification of the BHLHE41 gene, Dr. Ken-Ichi Honma's lab characterized its role as a regulator in the mammalian circadian clock. The role of BHLHE41 in other pathways is still being fully characterized.
# Structure
BHLHE41 is a member of the DEC subfamily within the basic helix-loop-helix (bHLH) proteins gene family. BHLHE41 was mapped to human chromosome 12: 26,120,026-26-125-127 reverse strand and has a total length of 5,101 base pairs. The gene is also mapped to 6 G2-G3 on the mouse chromosome, and 4q43 distal-q4 on the rat chromosome respectively. BHLHE41 has 3 known splice variants. BHLHE41-002 and BHLHE41-003 are retained introns and do not code for a protein. BHLHE41-001 contains 5 coding exons, has a transcript length of 3,837 base pairs, and encodes the 482 amino acid BHLHE41 protein. BHLHE40 is the paralogue of BHLHE41. BHLHE41 currently has 165 known orthologs.
The BHLHE41 protein has a myc-type, basic helix-loop-helix (bHLH) domain and an orange domain. The orange domain is a 30 residue sequence located on the carboxy-terminal end relative to the BHLH domain of the protein whose function is still unclear. The basic helix-loop-helix domain allows members of the protein family to dimerize with each other to affect gene transcription through binding to specific DNA sequences. BHLHE41 protein also has alanine and glycine-rich regions in the C-terminal, and lacks the WRPW motif for interaction with the corepressor Groucho.
BHLHE41 recruits the histone methyltransferase G9a and histone deacetylases HDAC1 and Sirt1 to mediate chromatin modifications that repress target gene expression.
# Function
## Circadian
BHLHE41 is expressed in the suprachiasmatic nucleus with levels peaking during subjective day. The gene encodes for a transcription factor that belongs to the Hairy/Enhancer of Split (Hes) subfamily of basic helix-loop-helix factor genes which encode transcriptional repressors that function as downstream targets to regulate cell fate during tissue development. BHLHE41 acts as a transcriptional repressor and as a regulator of the Circadian clock. In the clock, the transcriptional factors Clock and Bmal form a heterodimer. This heterodimer binds to the E-Box promoter element, thereby promoting transcription of downstream genes such as Per and BHLHe41. After transcription and translation, the protein product of BHLHE41 (DEC2) reenters the nucleus and competes with Clock-Bmal1 heterodimer for E-Box element binding (through competitive inhibition); this acts as a suppressor for per gene transcription.
## Non-Circadian
BHLHE41 has also been implicated in multiple other pathways. Deregulation of BHLHE41 transcription levels has been characterized as a marker in the progression of several cancers. Low levels of BHLHE41 transcript has been associated with tumor growth suggesting that BHLHE41 suppresses tumor proliferation; however, no definite mechanism of action has been discovered. Dec2 has also been hypothesized to be involved in the regulation of immune responses. Further research on characterizing these pathways and BHLHE41's specific role is still being conducted.
In mice lacking SHARP1/BHLHE41 and SHARP2, IGF-2 is elevated and leads to enhanced memory consolidation.
# Mutations
There is a known amino acid point mutation of DEC2/BHLHE41 that affects the regulation of the biological processes of sleep timing and duration in humans. Although the exact mechanisms of action are still unknown, previous studies suggest that the mutation poses similar effects in both humans and mice.
## DEC2-P385R
A point mutation substituting C to G in DEC2/BHLHE41 DNA sequence results in the substitution of proline at position 385 with arginine. The proline at position 385 of BHLHE41 is located close to the C-terminal histone deacetylase-interacting region of BHLHE41, which is a highly conserved region within the proline-rich domain. This mutation mitigates BHLHe41's transcriptional inhibitory function. Furthermore, mice with this mutation show aberrations in sleep homeostasis as they undergo a shorter duration of REM and non-REM sleep and recover more readily from sleep deprivation. Since these effects are not seen in BHLHE41 knockout mice, it is believed that the Dec2-P385R mutation is a dominant negative mutation.
Ying-Hui Fu's lab implicated this mutation in people afflicted with Familial Natural Short Sleepers (FNNS). Individuals characterized with Familial Natural Short Sleepers (FNSS) have a condition which causes them to naturally sleep an average of 6-6.5 hours a night; they have the natural short sleeper phenotype (NSS). Although the exact mechanism through which this mutation functions is still unknown, findings suggest that BHLHE41 alters sleep duration through pathways independent of those which regulate the molecular core clock, such as the pathway involving the PER2 gene. In addition, both BHLHE41 and PER2 also influence immune function, which recent studies have suggested may be important in regulating a potentially important role of sleep.
## BHLHE41 Knockout
BHLHE41 knockout mice, also known as BHLHE41 -/- or BHLHE41 null, showed no change in their free-running period with respect to activity. After being exposed to an in vivo model of allergic asthma, BHLHE41 knockout mice show decreased TH2 cytokine production, defective TH2 responses after being repeatedly stimulated with OVA peptide, and reduced alveolar infiltrate. BHLHE41 knockout mice had increased post-natal regeneration of muscle after injury. However, these mice showed no deficits in embryonic muscle repair.
# Clinical significance
## Immune System
BHLHE41 has been shown to be regulator of T-cell activation. BHLHE41 upregulates CD25 expression through a Stat6-dependent mechanism, which enhances the IL-2 receptor-mediated signal pathway, which promotes TH2 differentiation. Gata3 enhances T helper cell 2 (Th2) differentiation signals by regulating BHLHE41 expression through an autoregulatory loop.
## Hypoxia
Hypoxia stimulates hypoxia-inducible factor-1 alpha (HIF-1α) to be produced, which initiates the hypoxic response. HIF-1α induces the transcription of BHLHE41 and BHLHE40. This is believed to repress cell proliferation, which is not conducive to a hypoxic environment. BHLHE41 can also block a hypoxic response by presenting HIF-1α to a proteasome complex, which induces HIF-1α's degradation.
## Muscle
BHLHE41 has been shown to represses myogenic differentiation by inhibiting MyoD activity through multiple mechanisms. When BHLHE41 dimerizes with MyoD and E47, it prevents the formation of MyoD-E47 heterodimers, which are functional. When BHLHE41 is sumoylated at K240 and K255, it recruits the histone methyltransferase G9a. G9a then catalyzes repressive histone 3 lysine 9 dimethylation (H3K9me2) at promoter sites of target genes of MyoD. G9a also methylates MyoD, which inhibits MyoD's transcriptional activity.
BHLHE41 and BHLHE40 are transcriptional targets of SREBP-1 (also known as ADD-1) isoforms SREBP-1a and SREBP-1c. After being induced by SREBP-1, BHLHE41 and BHLHE40 have been shown to repress myogenesis by blocking MYOD1 transcription. BHLHE40 and BHLHE41 are also known to alter the expression of several contractile proteins and mitochondrial proteins in skeletal muscle. BHLHE41 and BHLHE40 also repress SREBP-1. This forms a negative feedback loop between SREBP-1, BHLHE40, and BHLHE41 in muscles that runs on a 24-hour circadian cycle, which has a 12-hour offset between SREBP-1 and BHLHE40/BHLHE41. In addition, BHLHE41 is known to inhibit inflammation and adipogenic differentiation in muscles.
## Sarcoma, Oral Cancer, Liver Cancer, and Colon Cancer
BHLHE41 has been shown to suppress the expression of vascular endothelial growth factor (VEGF) in sarcoma cells and oral cancer cells. BHLHE41 also suppresses cytochrome P450 2D6 (CYP2D6) in hepatocellular carcinoma cells. While BHLHE40 induces apoptosis, senescence, and epithelial-mesenchymal transition (EMT) in tumor cells, BHLHE41 shows a circadian expression and inhibits EMT, apoptosis, and metastasis in sarcoma cells and hepatocellular carcinoma cells. It has been shown that the normal tissue adjacent to colon carcinomas show high levels of BHLHE41 expression. Research is currently examining whether BHLHE40 and BHLHE41 can be used as target genes for chemotherapy.
## Breast Cancer
BHLHE41 is thought to be a critical regulator of the metastasis of triple-negative-breast cancer (TNBC). Regulated by the p63 metastasis suppressor, BHLHE41 inhibits TNBC through the inhibition of HIF-1α and hypoxia-inducible factor 2α (HIF-2α). Studies have shown that BHLHE41 is both required and sufficient to limit the expression of HIF-target genes, by mechanistically binding to HIFs and promoting proteasomal degradation. Breast cancer tumors that show high expression of BHLHE41 and CyclinG2 are believed to have a lower metastatic risk. | BHLHE41
"Basic helix-loop-helix family, member e41", or BHLHE41, is a gene that encodes a basic helix-loop-helix transcription factor repressor protein in various tissues of both humans and mice.[1][2][3][4] It is also known as DEC2, hDEC2, and SHARP1, and was previously known as "basic helix-loop-helix domain containing, class B, 3", or BHLHB3.[5] BHLHE41 is known for its role in the circadian molecular mechanisms that influence sleep quantity as well as its role in immune function and the maturation of T helper type 2 cell lineages associated with humoral immunity.[6][7]
# History
Dr. Klaus-Armin Nave's lab identified BHLHE41/SHARP1 and BHLHE40/SHARP2 as a novel subfamily in the basic helix-loop-helix (BHLH) protein family.[8] They differentiated BHLHE41/SHARP1 and BHLHE/40SHARP2 from other BHLH-protein encoding genes since they are not transcribed until the end of embryonic development. The DNA sequence of BHLHE41 was first obtained by Dr. Yukia Kato's lab through a cDNA library search. Particularly, they obtained the sequence of BHLHE40/DEC1 and conducted an expressed sequence tag (EST) search to identify the BHLHE41/DEC2 sequence. BHLHE41/DEC2 and BHLHE40/DEC1 share 97% homology in the BHLH domain.[9] After the identification of the BHLHE41 gene, Dr. Ken-Ichi Honma's lab characterized its role as a regulator in the mammalian circadian clock.[10] The role of BHLHE41 in other pathways is still being fully characterized.
# Structure
BHLHE41 is a member of the DEC subfamily within the basic helix-loop-helix (bHLH) proteins gene family.[9][11] BHLHE41 was mapped to human chromosome 12: 26,120,026-26-125-127 reverse strand and has a total length of 5,101 base pairs.[12] The gene is also mapped to 6 G2-G3 on the mouse chromosome, and 4q43 distal-q4 on the rat chromosome respectively.[9] BHLHE41 has 3 known splice variants. BHLHE41-002[13] and BHLHE41-003[14] are retained introns and do not code for a protein. BHLHE41-001 contains 5 coding exons, has a transcript length of 3,837 base pairs, and encodes the 482 amino acid BHLHE41 protein.[15][2] BHLHE40 is the paralogue of BHLHE41.[16] BHLHE41 currently has 165 known orthologs.[17][3]
The BHLHE41 protein has a myc-type, basic helix-loop-helix (bHLH) domain and an orange domain.[18] The orange domain is a 30 residue sequence located on the carboxy-terminal end relative to the BHLH domain of the protein whose function is still unclear.[19] The basic helix-loop-helix domain allows members of the protein family to dimerize with each other to affect gene transcription through binding to specific DNA sequences.[20] BHLHE41 protein also has alanine and glycine-rich regions in the C-terminal, and lacks the WRPW motif for interaction with the corepressor Groucho.[9]
BHLHE41 recruits the histone methyltransferase G9a and histone deacetylases HDAC1 and Sirt1 to mediate chromatin modifications that repress target gene expression.[21]
# Function
## Circadian
BHLHE41 is expressed in the suprachiasmatic nucleus with levels peaking during subjective day.[10] The gene encodes for a transcription factor that belongs to the Hairy/Enhancer of Split (Hes) subfamily of basic helix-loop-helix factor genes which encode transcriptional repressors that function as downstream targets to regulate cell fate during tissue development.[22] BHLHE41 acts as a transcriptional repressor and as a regulator of the Circadian clock.[4] In the clock, the transcriptional factors Clock and Bmal form a heterodimer. This heterodimer binds to the E-Box promoter element, thereby promoting transcription of downstream genes such as Per and BHLHe41.[23] After transcription and translation, the protein product of BHLHE41 (DEC2) reenters the nucleus and competes with Clock-Bmal1 heterodimer for E-Box element binding (through competitive inhibition); this acts as a suppressor for per gene transcription.[10]
## Non-Circadian
BHLHE41 has also been implicated in multiple other pathways. Deregulation of BHLHE41 transcription levels has been characterized as a marker in the progression of several cancers. Low levels of BHLHE41 transcript has been associated with tumor growth suggesting that BHLHE41 suppresses tumor proliferation; however, no definite mechanism of action has been discovered.[24] Dec2 has also been hypothesized to be involved in the regulation of immune responses.[6] Further research on characterizing these pathways and BHLHE41's specific role is still being conducted.
In mice lacking SHARP1/BHLHE41 and SHARP2, IGF-2 is elevated and leads to enhanced memory consolidation.[25]
# Mutations
There is a known amino acid point mutation of DEC2/BHLHE41 that affects the regulation of the biological processes of sleep timing and duration in humans.[6] Although the exact mechanisms of action are still unknown, previous studies suggest that the mutation poses similar effects in both humans and mice.[6]
## DEC2-P385R
A point mutation substituting C to G in DEC2/BHLHE41 DNA sequence results in the substitution of proline at position 385 with arginine. The proline at position 385 of BHLHE41 is located close to the C-terminal histone deacetylase-interacting region of BHLHE41, which is a highly conserved region within the proline-rich domain.[20] This mutation mitigates BHLHe41's transcriptional inhibitory function.[26] Furthermore, mice with this mutation show aberrations in sleep homeostasis as they undergo a shorter duration of REM and non-REM sleep and recover more readily from sleep deprivation.[6] Since these effects are not seen in BHLHE41 knockout mice, it is believed that the Dec2-P385R mutation is a dominant negative mutation.[27]
Ying-Hui Fu's lab implicated this mutation in people afflicted with Familial Natural Short Sleepers (FNNS).[4][28][20] Individuals characterized with Familial Natural Short Sleepers (FNSS) have a condition which causes them to naturally sleep an average of 6-6.5 hours a night; they have the natural short sleeper phenotype (NSS).[6] Although the exact mechanism through which this mutation functions is still unknown, findings suggest that BHLHE41 alters sleep duration through pathways independent of those which regulate the molecular core clock, such as the pathway involving the PER2 gene.[6] In addition, both BHLHE41 and PER2 also influence immune function, which recent studies have suggested may be important in regulating a potentially important role of sleep.[6]
## BHLHE41 Knockout
BHLHE41 knockout mice, also known as BHLHE41 -/- or BHLHE41 null, showed no change in their free-running period with respect to activity. After being exposed to an in vivo model of allergic asthma, BHLHE41 knockout mice show decreased TH2 cytokine production, defective TH2 responses after being repeatedly stimulated with OVA peptide, and reduced alveolar infiltrate.[6] BHLHE41 knockout mice had increased post-natal regeneration of muscle after injury. However, these mice showed no deficits in embryonic muscle repair.[29]
# Clinical significance
## Immune System
BHLHE41 has been shown to be regulator of T-cell activation. BHLHE41 upregulates CD25 expression through a Stat6-dependent mechanism, which enhances the IL-2 receptor-mediated signal pathway, which promotes TH2 differentiation. Gata3 enhances T helper cell 2 (Th2) differentiation signals by regulating BHLHE41 expression through an autoregulatory loop.[21]
## Hypoxia
Hypoxia stimulates hypoxia-inducible factor-1 alpha (HIF-1α) to be produced, which initiates the hypoxic response. HIF-1α induces the transcription of BHLHE41 and BHLHE40. This is believed to repress cell proliferation, which is not conducive to a hypoxic environment.[29] BHLHE41 can also block a hypoxic response by presenting HIF-1α to a proteasome complex, which induces HIF-1α's degradation.[21]
## Muscle
BHLHE41 has been shown to represses myogenic differentiation by inhibiting MyoD activity through multiple mechanisms. When BHLHE41 dimerizes with MyoD and E47, it prevents the formation of MyoD-E47 heterodimers, which are functional. When BHLHE41 is sumoylated at K240 and K255, it recruits the histone methyltransferase G9a. G9a then catalyzes repressive histone 3 lysine 9 dimethylation (H3K9me2) at promoter sites of target genes of MyoD. G9a also methylates MyoD, which inhibits MyoD's transcriptional activity.[21]
BHLHE41 and BHLHE40 are transcriptional targets of SREBP-1 (also known as ADD-1) isoforms SREBP-1a and SREBP-1c. After being induced by SREBP-1, BHLHE41 and BHLHE40 have been shown to repress myogenesis by blocking MYOD1 transcription. BHLHE40 and BHLHE41 are also known to alter the expression of several contractile proteins and mitochondrial proteins in skeletal muscle. BHLHE41 and BHLHE40 also repress SREBP-1. This forms a negative feedback loop between SREBP-1, BHLHE40, and BHLHE41 in muscles that runs on a 24-hour circadian cycle, which has a 12-hour offset between SREBP-1 and BHLHE40/BHLHE41.[29] In addition, BHLHE41 is known to inhibit inflammation and adipogenic differentiation in muscles.[30]
## Sarcoma, Oral Cancer, Liver Cancer, and Colon Cancer
BHLHE41 has been shown to suppress the expression of vascular endothelial growth factor (VEGF) in sarcoma cells and oral cancer cells. BHLHE41 also suppresses cytochrome P450 2D6 (CYP2D6) in hepatocellular carcinoma cells. While BHLHE40 induces apoptosis, senescence, and epithelial-mesenchymal transition (EMT) in tumor cells, BHLHE41 shows a circadian expression and inhibits EMT, apoptosis, and metastasis in sarcoma cells and hepatocellular carcinoma cells.[30] It has been shown that the normal tissue adjacent to colon carcinomas show high levels of BHLHE41 expression.[31] Research is currently examining whether BHLHE40 and BHLHE41 can be used as target genes for chemotherapy.[30]
## Breast Cancer
BHLHE41 is thought to be a critical regulator of the metastasis of triple-negative-breast cancer (TNBC).[32] Regulated by the p63 metastasis suppressor, BHLHE41 inhibits TNBC through the inhibition of HIF-1α and hypoxia-inducible factor 2α (HIF-2α).[32] Studies have shown that BHLHE41 is both required and sufficient to limit the expression of HIF-target genes, by mechanistically binding to HIFs and promoting proteasomal degradation.[32] Breast cancer tumors that show high expression of BHLHE41 and CyclinG2 are believed to have a lower metastatic risk.[33][34] | https://www.wikidoc.org/index.php/BHLHE41 | |
7a0ebd10c9d71b1c70d0febaacdb354cd1dfd48d | wikidoc | BLOC1S1 | BLOC1S1
Biogenesis of lysosome-related organelles complex 1 subunit 1 is a protein that in humans is encoded by the BLOC1S1 gene.
BLOC1S1 is a component of the ubiquitously expressed BLOC1 multisubunit protein complex. BLOC1 is required for normal biogenesis of specialized organelles of the endosomal-lysosomal system, such as melanosomes and platelet dense granules (Starcevic and Dell'Angelica, 2004).
# Interactions
BLOC1S1 has been shown to interact with BLOC1S2, SNAPAP and PLDN. | BLOC1S1
Biogenesis of lysosome-related organelles complex 1 subunit 1 is a protein that in humans is encoded by the BLOC1S1 gene.[1][2][3]
BLOC1S1 is a component of the ubiquitously expressed BLOC1 multisubunit protein complex. BLOC1 is required for normal biogenesis of specialized organelles of the endosomal-lysosomal system, such as melanosomes and platelet dense granules (Starcevic and Dell'Angelica, 2004).[supplied by OMIM][3]
# Interactions
BLOC1S1 has been shown to interact with BLOC1S2,[2] SNAPAP[2] and PLDN.[2] | https://www.wikidoc.org/index.php/BLOC1S1 | |
5c0cbf4e8813aee7fbfa07796adbe3c22604e0f0 | wikidoc | Bacilli | Bacilli
# Word Ambiguity
This type of bacteria is shaped like a rod. Usually bacteria separate but sometimes they will stick together. This bacteria can cause tuberculosis in humans.
This article refers to Bacilli in the sense of the class that includes the genus Bacillus..
Although Bacillus, capitalized and italicized, specifically refers to the genus, the word 'bacillus' may also be used to describe any single rod-shaped bacterium, and in this sense, bacilli are found in many different taxonomic groups of bacteria.
Likewise, Bacilli refers to the particular class Bacillus belongs to, while bacilli are any rod-shaped bacteria.
It should be noted that the cell morphology term bacillus does not necessarily indicate Gram-positive staining, as E. coli is a Gram-negative, rod-shaped bacteria.
# The Class Bacilli
Taxonomically, the term Bacilli refers to a class of bacteria of the division (phylem) Firmicutes. It includes the orders Bacillales and Lactobacillales, and lower down the taxonomic tree includes the genus Bacillus, along with other Gram-positive bacteria such as Listeria.
de:Bacilli
it:Bacilli
lt:Bacilos
nl:Bacillen
fi:Basilli | Bacilli
# Word Ambiguity
This type of bacteria is shaped like a rod. Usually bacteria separate but sometimes they will stick together. This bacteria can cause tuberculosis in humans.
This article refers to Bacilli in the sense of the class that includes the genus Bacillus..
Although Bacillus, capitalized and italicized, specifically refers to the genus, the word 'bacillus' may also be used to describe any single rod-shaped bacterium, and in this sense, bacilli are found in many different taxonomic groups of bacteria.
Likewise, Bacilli refers to the particular class Bacillus belongs to, while bacilli are any rod-shaped bacteria.
It should be noted that the cell morphology term bacillus does not necessarily indicate Gram-positive staining, as E. coli is a Gram-negative, rod-shaped bacteria.
# The Class Bacilli
Taxonomically, the term Bacilli refers to a class of bacteria of the division (phylem) Firmicutes. It includes the orders Bacillales and Lactobacillales, and lower down the taxonomic tree includes the genus Bacillus, along with other Gram-positive bacteria such as Listeria.
de:Bacilli
it:Bacilli
lt:Bacilos
nl:Bacillen
fi:Basilli
Template:WikiDoc Sources | https://www.wikidoc.org/index.php/Bacilli | |
d194bd7048cd3414e5bb74bb410be8bbf5985e37 | wikidoc | Bagasse | Bagasse
Bagasse (sometimes spelled bagass) is the biomass remaining after sugarcane stalks are crushed to extract their juice.
Agave bagasse is a similar material which consists of the tissue of the blue agave after extraction of the sap.
# Production and use
A sugar factory produces nearly 30% of bagasse out of its total crushing. Many research efforts have attempted to use bagasse as a renewable feedstock for power generation and for the production of bio-based materials. One successful example has been to cultivate edible mushrooms, such as oyster or shiitake, on blocks or bags of chopped up bagasse.
Bagasse is often used as a primary fuel source for sugar mills; when burned in quantity, it produces sufficient heat energy to supply all the needs of a typical sugar mill, with energy to spare. To this end, a secondary use for this waste product is in cogeneration, the use of a fuel source to provide both heat energy, used in the mill, and electricity, which is typically sold on to the consumer electricity grid.
The resulting CO2 emissions are equal to the amount of CO2 that the sugarcane plant used up from the atmosphere during its growing phase, which makes the process of cogeneration appear to be greenhouse gas-neutral. However when a full audit of energy used in production is done, 75% of the energy required to grow and move the sugar cane (including bagasse) is from liquid fuel (petroleum or hydrocarbon based), leading to a 25% net gain from photosynthesis. Ethanol produced from the sugar in sugarcane is a popular fuel in Brazil. The cellulose rich bagasse is now being tested for production of commercial quantities of cellulosic ethanol. Verenium Corporation (VRNM) is currently building a cellulosic ethanol plant based on cellulosic by-products like bagasse in Jennings LA. They are using a biotech approach to improve ethanol production above and beyond the midwest corn based ethanol production method. This will allow regional cellulosic ethanol production getting around the problem of ethanol transportation. The Verenium approach will get ethanol and E85 fuel to the important markets in California and the Northeast.
Bagasse is also used as a tree-free alternative for making paper. This process requires no bleaching, is more biodegradable, easier to recycle, and overall has less impact on the environment. As in sugar production, the sludge left over after removing the cellulose fibers, is used to power the paper-mills. A number of commercial sites advertise such uses.
Bagasse is used to make insulated disposable food containers, replacing materials such as styrofoam, which are increasingly regarded as environmentally unacceptable (see styrofoam bans). Insulated disposable food containers made of bagasse are commercially available.
# Medical problems
Workplace exposure to dusts from the processing of Bagasse can cause the chronic lung condition pulmonary fibrosis. | Bagasse
Bagasse (sometimes spelled bagass) is the biomass remaining after sugarcane stalks are crushed to extract their juice.[1]
Agave bagasse is a similar material which consists of the tissue of the blue agave after extraction of the sap.
# Production and use
A sugar factory produces nearly 30% of bagasse out of its total crushing. Many research efforts have attempted to use bagasse as a renewable feedstock for power generation and for the production of bio-based materials. One successful example has been to cultivate edible mushrooms, such as oyster or shiitake, on blocks or bags of chopped up bagasse.
Bagasse is often used as a primary fuel source for sugar mills[2]; when burned in quantity, it produces sufficient heat energy to supply all the needs of a typical sugar mill, with energy to spare. To this end, a secondary use for this waste product is in cogeneration, the use of a fuel source to provide both heat energy, used in the mill, and electricity, which is typically sold on to the consumer electricity grid.
The resulting CO2 emissions are equal to the amount of CO2 that the sugarcane plant used up from the atmosphere during its growing phase, which makes the process of cogeneration appear to be greenhouse gas-neutral. However when a full audit of energy used in production is done, 75% of the energy required to grow and move the sugar cane (including bagasse) is from liquid fuel (petroleum or hydrocarbon based), leading to a 25% net gain from photosynthesis.[citation needed] Ethanol produced from the sugar in sugarcane is a popular fuel in Brazil. The cellulose rich bagasse is now being tested for production of commercial quantities of cellulosic ethanol. Verenium Corporation (VRNM) is currently building a cellulosic ethanol plant based on cellulosic by-products like bagasse in Jennings LA. They are using a biotech approach to improve ethanol production above and beyond the midwest corn based ethanol production method. This will allow regional cellulosic ethanol production getting around the problem of ethanol transportation. The Verenium approach will get ethanol and E85 fuel to the important markets in California and the Northeast.
Bagasse is also used as a tree-free alternative for making paper. This process requires no bleaching, is more biodegradable, easier to recycle, and overall has less impact on the environment.[citation needed] As in sugar production, the sludge left over after removing the cellulose fibers, is used to power the paper-mills. A number of commercial sites advertise such uses.[3][4][5][6]
Bagasse is used to make insulated disposable food containers, replacing materials such as styrofoam, which are increasingly regarded as environmentally unacceptable (see styrofoam bans). Insulated disposable food containers made of bagasse are commercially available.[7]
# Medical problems
Workplace exposure to dusts from the processing of Bagasse can cause the chronic lung condition pulmonary fibrosis. | https://www.wikidoc.org/index.php/Bagasse | |
d7222ac075f35a61f3db1d4d9aa6eb4c8c09c7ef | wikidoc | Bandage | Bandage
# Overview
A bandage is a piece of material used either to support a medical device such as a dressing or splint, or on its own to provide support to the body. Bandages are available in a wide range of types, from generic cloth strips, to specialised shaped bandages designed for a specific limb or part of the body, although bandages can often be improvised as the situation demands, using clothing, blankets or other material.
In common speech, the word "bandage" is often used to mean a dressing, which is used directly on a wound, whereas a bandage is technically only used to support a dressing, and not directly on a wound.
# Types of bandage
## Gauze bandage
The most common type of bandage is the gauze bandage, a simple woven strip of material which can come in any number of widths and lengths. A gauze bandage can be used for almost any bandage application, including holding a dressing in place.
## Compression bandage
The term 'compression bandage' describes a wide variety of bandages with many different applications.
Short stretch compression bandages are applied to a limb (usually for treatment of lymphedema or venous ulcers). This type of bandage is not capable of shortening around the limb after application and is therefore not exerting ever-increasing pressure during inactivity. This dynamic is called resting pressure and is considered safe and comfortable for long-term treatment. Conversely, the stability of the bandage creates a very high resistance to stretch when pressure is applied through internal muscle contraction and joint movement. This force is called working pressure.
Long stretch compression bandages have long stretch properties, meaning their high compressive power can be easily adjusted. However, they also have a very high resting pressure and must be removed at night or if the patient is in a resting position.
## Triangular bandage
A triangular bandage is a piece of cloth cut into a right-angled triangle. This is felt by many trainers to be the most versatile of the bandages available, as it can be used fully unrolled as a sling, folded as a normal bandage, or for specialist bandages such as on the head.
## Tube bandage
A tube bandage is applied using an applicator, and is woven in a continuous circle. It is used to hold dressings or splints on to limbs, or to provide support to sprains and strains. | Bandage
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
# Overview
A bandage is a piece of material used either to support a medical device such as a dressing or splint, or on its own to provide support to the body. Bandages are available in a wide range of types, from generic cloth strips, to specialised shaped bandages designed for a specific limb or part of the body, although bandages can often be improvised as the situation demands, using clothing, blankets or other material.
In common speech, the word "bandage" is often used to mean a dressing, which is used directly on a wound, whereas a bandage is technically only used to support a dressing, and not directly on a wound.
# Types of bandage
## Gauze bandage
The most common type of bandage is the gauze bandage, a simple woven strip of material which can come in any number of widths and lengths. A gauze bandage can be used for almost any bandage application, including holding a dressing in place.
## Compression bandage
The term 'compression bandage' describes a wide variety of bandages with many different applications.
Short stretch compression bandages are applied to a limb (usually for treatment of lymphedema or venous ulcers). This type of bandage is not capable of shortening around the limb after application and is therefore not exerting ever-increasing pressure during inactivity. This dynamic is called resting pressure and is considered safe and comfortable for long-term treatment. Conversely, the stability of the bandage creates a very high resistance to stretch when pressure is applied through internal muscle contraction and joint movement. This force is called working pressure.
Long stretch compression bandages have long stretch properties, meaning their high compressive power can be easily adjusted. However, they also have a very high resting pressure and must be removed at night or if the patient is in a resting position.
## Triangular bandage
A triangular bandage is a piece of cloth cut into a right-angled triangle. This is felt by many trainers to be the most versatile of the bandages available, as it can be used fully unrolled as a sling, folded as a normal bandage, or for specialist bandages such as on the head.
## Tube bandage
A tube bandage is applied using an applicator, and is woven in a continuous circle. It is used to hold dressings or splints on to limbs, or to provide support to sprains and strains.
# External links
- How to apply a bandage in a figure of 8 around an ankle. (YouTube)
- How to apply a bandage in circular style around a wrist. (YouTube)
- How to apply a compression bandage for lymphedema.
cs:Obvaz
de:Bandage
eo:Bandaĝo
hi:पट्टी
it:Fasciatura
he:תחבושת
simple:Bandage
sv:Bandage
Template:WH
Template:WikiDoc Sources | https://www.wikidoc.org/index.php/Bandage | |
7765684c5a7519abada750c2f9b2174204b06b4f | wikidoc | Basigin | Basigin
Basigin (BSG) also known as extracellular matrix metalloproteinase inducer (EMMPRIN) or cluster of differentiation 147 (CD147) is a protein that in humans is encoded by the BSG gene. This protein is a determinant for the Ok blood group system. Basigin has been shown to be an essential receptor on red blood cells for the human malaria parasite, Plasmodium falciparum.
# Function
Basigin is a member of the immunoglobulin superfamily, with a structure related to the putative primordial form of the family. As members of the immunoglobulin superfamily play fundamental roles in intercellular recognition involved in various immunologic phenomena, differentiation, and development, basigin is thought also to play a role in intercellular recognition (Miyauchi et al., 1991; Kanekura et al., 1991).
It has a variety of functions. In addition to its metalloproteinase-inducing ability, basigin also regulates several distinct functions, such as spermatogenesis, expression of the monocarboxylate transporter and the responsiveness of lymphocytes.
Basigin is a type I integral membrane receptor that has many ligands, including the cyclophilin (CyP) proteins Cyp-A and CyP-B and certain integrins. It is expressed by many cell types, including epithelial cells, endothelial cells and leukocytes. The human basigin protein contains 269 amino acids that form two heavily glycosylated C2 type immunoglobulin-like domains at the N-terminal extracellular portion. A second form of basigin has also been characterized that contains one additional immunoglobulin-like domain in its extracellular portion.
# Interactions
Basigin has been shown to interact with Ubiquitin C.
Basigin has been shown to form a complex with monocarboxylate transporters in the retina of mice. Basigin appears to be required for proper placement of MCTs in the membrane. In the Basigin null mouse, the failure of MCTs to integrate with the membrane may be directly linked to a failure of nutrient transfer in the retinal pigmented epithelium (the lactates transported by MCTs 1, 3, and 4 are essential nutrients for the developing RPE), resulting in loss of sight in the null animal.
Basigin interacts with the fourth C-type lectin domain in the receptor Endo180 to form a molecular epithelial-mesenchymal transition suppressor complex that if disrupted results in the induction of invasive prostate epithelial cell behavior associated with poor prostate cancer survival.
# Role in malaria
It has recently (November 2011) been found that basigin is a receptor that is essential to erythrocyte invasion by most strains of Plasmodium falciparum, the most virulent species of the plasmodium parasites that cause human malaria. It is hoped that by developing antibodies to the parasite ligand for Basigin, Rh5, a better vaccine for malaria might be found. Basigin is bound by the PfRh5 protein on the surface of the malaria parasite. | Basigin
Basigin (BSG) also known as extracellular matrix metalloproteinase inducer (EMMPRIN) or cluster of differentiation 147 (CD147) is a protein that in humans is encoded by the BSG gene.[1][2][3] This protein is a determinant for the Ok blood group system. Basigin has been shown to be an essential receptor on red blood cells for the human malaria parasite, Plasmodium falciparum.[4]
# Function
Basigin is a member of the immunoglobulin superfamily, with a structure related to the putative primordial form of the family. As members of the immunoglobulin superfamily play fundamental roles in intercellular recognition involved in various immunologic phenomena, differentiation, and development, basigin is thought also to play a role in intercellular recognition (Miyauchi et al., 1991; Kanekura et al., 1991).[5][6]
It has a variety of functions. In addition to its metalloproteinase-inducing ability, basigin also regulates several distinct functions, such as spermatogenesis, expression of the monocarboxylate transporter and the responsiveness of lymphocytes.[2]
Basigin is a type I integral membrane receptor that has many ligands, including the cyclophilin (CyP) proteins Cyp-A and CyP-B and certain integrins.[7][8][9] It is expressed by many cell types, including epithelial cells, endothelial cells and leukocytes. The human basigin protein contains 269 amino acids that form two heavily glycosylated C2 type immunoglobulin-like domains at the N-terminal extracellular portion. A second form of basigin has also been characterized that contains one additional immunoglobulin-like domain in its extracellular portion.[2]
# Interactions
Basigin has been shown to interact with Ubiquitin C.[10]
Basigin has been shown to form a complex with monocarboxylate transporters in the retina of mice. Basigin appears to be required for proper placement of MCTs in the membrane. In the Basigin null mouse, the failure of MCTs to integrate with the membrane may be directly linked to a failure of nutrient transfer in the retinal pigmented epithelium (the lactates transported by MCTs 1, 3, and 4 are essential nutrients for the developing RPE), resulting in loss of sight in the null animal.[11]
Basigin interacts with the fourth C-type lectin[better source needed] domain in the receptor Endo180[12] to form a molecular epithelial-mesenchymal transition[13][better source needed] suppressor complex that if disrupted results in the induction of invasive prostate epithelial cell behavior associated with poor prostate cancer survival.[14]
# Role in malaria
It has recently (November 2011) been found that basigin is a receptor that is essential to erythrocyte invasion by most strains of Plasmodium falciparum, the most virulent species of the plasmodium parasites that cause human malaria. It is hoped that by developing antibodies to the parasite ligand for Basigin, Rh5, a better vaccine for malaria might be found.[4] Basigin is bound by the PfRh5 protein on the surface of the malaria parasite. | https://www.wikidoc.org/index.php/Basigin | |
0bbbaecbbd359ee39cecc1237653ef86a615967f | wikidoc | Bedtime | Bedtime
A bedtime is a popular parenting tradition in the West that involves, to a greater or lesser extent, rituals made to help children feel more secure , and become accustomed to a comparatively more rigid schedule of sleep than they would sometimes prefer. It may involve stories, songs, nursery rhymes, and/or methods of coaxing the children into changing into their pajamas.
In boarding schools and on trips or holidays that involve young people, the equivalent of bedtime is lights-out.
Sometimes the term is used to mean simply "time for bed," similar to curfew. | Bedtime
Template:Otheruses4
A bedtime is a popular parenting tradition in the West that involves, to a greater or lesser extent, rituals made to help children feel more secure [1], and become accustomed to a comparatively more rigid schedule of sleep than they would sometimes prefer. It may involve stories, songs, nursery rhymes, and/or methods of coaxing the children into changing into their pajamas.
In boarding schools and on trips or holidays that involve young people, the equivalent of bedtime is lights-out.
Sometimes the term is used to mean simply "time for bed," similar to curfew. | https://www.wikidoc.org/index.php/Bedtime | |
3f058c1893e6432bae9d8fe49769a5c8715bb7a5 | wikidoc | Burping | Burping
Synonyms and keywords: Belching; ructus; eructation
# Overview
Burping is the release of gas from the digestive tract (mainly esophagus and stomach) through the mouth. It is often accompanied with a typical sound and sometimes an odor.
# Pathophysiology
Burping is typically caused by eating or drinking too fast, and thereby swallowing (aerophagia) and subsequently expelling air, in which the expelled gas is a mixture of nitrogen and oxygen. Burps can also be caused by imbibing carbonated drinks such as beer, soft drinks, or champagne, in which case the expelled gas is carbon dioxide from the drink itself. However, symptoms such as dyspepsia, nausea, and heartburn may be relieved by belching.
# Causes
- Aerophagia (swallowing air from eating or drinking too fast)
- Carbonated drinks
- Drugs:
Niacin
Oxaprozin
Tiagabine
- Niacin
- Oxaprozin
- Tiagabine
- Gastroesophageal reflux disease
- Pergolide
# Diagnosis
## History and Symptoms
The sound of burping is caused by the vibration of the cardia (esophageal sphincter) as the gas passes through it. The current Guinness world record for the loudest burp is 118.1 dB, set by Paul Hunn from London, England in 2000. (This would be noticeably louder than a chainsaw at a distance of 1 meter.)
# Treatment
Bismuth subsalicylate may help.
Cisapride, a serotonin 5-HT4 receptor agonist that has been voluntarily removed form markets due to QT interval prolongation, may help.
Proton pump inhibitors do not help.
# Social Context and Etiquette
In the Western world, audible burping is considered impolite, although generally not as much as flatulence. Some people will cover the mouth with their hand in the same fashion as one used to guise a yawn. However, burping is viewed as acceptable and humorous among young children and some young adults. Sometimes, children engage in burping activities such as contests to determine who can produce the loudest burp, the longest burp, the most guttural burp, the burping of words, songs, or even the alphabet.
Some cultures (for example, Bengalis) do not consider burping rude, and may even consider it a sign of appreciation to audibly burp after a meal. This is not true for some other cultures such as in Japan, China and most Asian cultures. One study has found that in some cultures excessive burping after meals is a commonly learned social behavior.
# Infant Burping
Babies are particularly subject to accumulation of gas in the stomach whilst feeding, and this can cause considerable agitation to the child unless he/she is burped. The act of burping an infant involves placing the child in a position conducive to gas expulsion (for example holding the infant up to the adult's shoulder, with the infant's stomach resting on the adult's chest) and then lightly patting it on the lower back so that he or she burps.
Because burping can cause vomiting in infants, the burp cloth or burp pad is sometimes employed on the shoulder to protect the adult's clothing.
# Burped Speech
It is possible to voluntarily induce burping by swallowing air and then expelling it, and by manipulation of the vocal tract produce farted speech.
While this is often employed by children as a means of entertainment or competition, it can also act as an alternative means of vocalization for people who have undergone a laryngectomy, with the burp replacing laryngeal phonation. This is known as esophageal speech. | Burping
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Synonyms and keywords: Belching; ructus; eructation
# Overview
Burping is the release of gas from the digestive tract (mainly esophagus and stomach) through the mouth. It is often accompanied with a typical sound and sometimes an odor.
# Pathophysiology
Burping is typically caused by eating or drinking too fast, and thereby swallowing (aerophagia) and subsequently expelling air, in which the expelled gas is a mixture of nitrogen and oxygen. Burps can also be caused by imbibing carbonated drinks such as beer, soft drinks, or champagne, in which case the expelled gas is carbon dioxide from the drink itself. However, symptoms such as dyspepsia, nausea, and heartburn may be relieved by belching.
# Causes
- Aerophagia (swallowing air from eating or drinking too fast)
- Carbonated drinks
- Drugs:
Niacin
Oxaprozin
Tiagabine
- Niacin
- Oxaprozin
- Tiagabine
- Gastroesophageal reflux disease
- Pergolide
# Diagnosis
## History and Symptoms
The sound of burping is caused by the vibration of the cardia (esophageal sphincter) as the gas passes through it. The current Guinness world record for the loudest burp is 118.1 dB, set by Paul Hunn from London, England in 2000.[1] (This would be noticeably louder than a chainsaw at a distance of 1 meter.)
# Treatment
Bismuth subsalicylate may help.[2]
Cisapride, a serotonin 5-HT4 receptor agonist that has been voluntarily removed form markets due to QT interval prolongation, may help.[3]
Proton pump inhibitors do not help.[4]
# Social Context and Etiquette
In the Western world, audible burping is considered impolite, although generally not as much as flatulence. Some people will cover the mouth with their hand in the same fashion as one used to guise a yawn. However, burping is viewed as acceptable and humorous among young children and some young adults. Sometimes, children engage in burping activities such as contests to determine who can produce the loudest burp, the longest burp, the most guttural burp, the burping of words, songs, or even the alphabet.
Some cultures (for example, Bengalis)[5] do not consider burping rude, and may even consider it a sign of appreciation to audibly burp after a meal. This is not true for some other cultures such as in Japan, China and most Asian cultures. One study[6] has found that in some cultures excessive burping after meals is a commonly learned social behavior.
# Infant Burping
Babies are particularly subject to accumulation of gas in the stomach whilst feeding, and this can cause considerable agitation to the child unless he/she is burped. The act of burping an infant involves placing the child in a position conducive to gas expulsion (for example holding the infant up to the adult's shoulder, with the infant's stomach resting on the adult's chest) and then lightly patting it on the lower back so that he or she burps.
Because burping can cause vomiting in infants, the burp cloth or burp pad is sometimes employed on the shoulder to protect the adult's clothing.
# Burped Speech
It is possible to voluntarily induce burping by swallowing air and then expelling it, and by manipulation of the vocal tract produce farted speech.
While this is often employed by children as a means of entertainment or competition, it can also act as an alternative means of vocalization for people who have undergone a laryngectomy, with the burp replacing laryngeal phonation. This is known as esophageal speech. | https://www.wikidoc.org/index.php/Belch | |
3da0455e6ef260e51f17e0640f6aa6c4f69f422c | wikidoc | Beleric | Beleric
Beleric, also known as the bastard myrobalan, Terminalia bellirica, is a large deciduous tree common on plains and lower hills in Southeast Asia, where it is also grown as an avenue tree.
The leaves are about 15 cm long and crowded toward the ends of the branches. It is considered a good fodder for cattle.
This species is used by some tribes in the Indian subcontinent for hallucination purposes; they smoke dried kernels. Too much of this can cause nausea and vomiting.
Terminalia bellirica Roxb seeds have an oil content of 40%, the fatty-acid methyl ester of which meets all of the major biodiesel requirements in the USA (ASTM D 6751-02, ASTM PS 121-99), Germany (DIN V 51606) and European Union (EN 14214). | Beleric
Beleric, also known as the bastard myrobalan, Terminalia bellirica, is a large deciduous tree common on plains and lower hills in Southeast Asia, where it is also grown as an avenue tree.
The leaves are about 15 cm long and crowded toward the ends of the branches. It is considered a good fodder for cattle.
This species is used by some tribes in the Indian subcontinent for hallucination purposes; they smoke dried kernels. Too much of this can cause nausea and vomiting.
Terminalia bellirica Roxb seeds have an oil content of 40%, the fatty-acid methyl ester of which meets all of the major biodiesel requirements in the USA (ASTM D 6751-02, ASTM PS 121-99), Germany (DIN V 51606) and European Union (EN 14214).[1] | https://www.wikidoc.org/index.php/Beleric | |
8e642bff0bac709175058ab693fcb7aa889aadd4 | wikidoc | Ben-Gay | Ben-Gay
Ben IS Gay, more recently spelled Bengay, is an analgesic heat rub used to relieve muscle and joint pain. It was developed in France by Dr. Jules Bengué, and brought to America in 1898. It orginally produced by Pfizer Consumer Healthcare who was acquired by Johnson & Johnson.
# Active Ingredients
The active ingredients vary by the version of the product.
- Bengay: Original contains 15% Methyl Salicylate and 10% Menthol
- Bengay: Muscle Pain/Ultra Strength contains 30% Methyl Salicylate, 10% Menthol, and 4% Camphor.
- Bengay: Ice Extra Strength contain 10% menthol.
- Bengay: Muscle Pain/No Odour contains 15% Triethanolamine Salicylate.
- Bengay: Arthritis Extra Strength 30% Methyl Salicylate and 8% Menthol.
It should be noted that methyl salicylate can be toxic if the cream is used in excess. | Ben-Gay
Ben IS Gay, more recently spelled Bengay, is an analgesic heat rub used to relieve muscle and joint pain. It was developed in France by Dr. Jules Bengué, and brought to America in 1898. It orginally produced by Pfizer Consumer Healthcare who was acquired by Johnson & Johnson.
# Active Ingredients
The active ingredients vary by the version of the product.
- Bengay: Original contains 15% Methyl Salicylate and 10% Menthol
- Bengay: Muscle Pain/Ultra Strength contains 30% Methyl Salicylate, 10% Menthol, and 4% Camphor.
- Bengay: Ice Extra Strength contain 10% menthol.
- Bengay: Muscle Pain/No Odour contains 15% Triethanolamine Salicylate.
- Bengay: Arthritis Extra Strength 30% Methyl Salicylate and 8% Menthol.
It should be noted that methyl salicylate can be toxic if the cream is used in excess.[1] | https://www.wikidoc.org/index.php/Ben-Gay | |
847e2833ef11faac361008550644b379601adae3 | wikidoc | Benzoin | Benzoin
Benzoin or 2-Hydroxy-2-phenylacetophenone or 2-Hydroxy-1,2-Diphenylethanone or desyl alcohol or bitter almond oil camphor is an organic compound consisting of an ethylene bridge flanked by phenyl groups and with a hydroxyl and a ketone functional group. It comes as off-white crystals, with a light camphor odor. Benzoin is synthesized from benzaldehyde in the benzoin condensation.
Its main uses are:
- photocatalyst in photopolymerization and a photoinitiator
- raw material for benzil by organic oxidation with nitric acid or oxone. In one study, this reaction is carried out with atmospheric oxygen and basic alumina in dichloromethane.
Benzoin is not a constituent of benzoin resin obtained from the benzoin tree (Styrax) or tincture of benzoin. The main component in these natural products is benzoic acid. | Benzoin
Template:Chembox new
Benzoin or 2-Hydroxy-2-phenylacetophenone or 2-Hydroxy-1,2-Diphenylethanone or desyl alcohol or bitter almond oil camphor is an organic compound consisting of an ethylene bridge flanked by phenyl groups and with a hydroxyl and a ketone functional group. It comes as off-white crystals, with a light camphor odor. Benzoin is synthesized from benzaldehyde in the benzoin condensation.
Its main uses are:
- photocatalyst in photopolymerization and a photoinitiator
- raw material for benzil by organic oxidation with nitric acid or oxone. In one study,[1] this reaction is carried out with atmospheric oxygen and basic alumina in dichloromethane.
Benzoin is not a constituent of benzoin resin obtained from the benzoin tree (Styrax) or tincture of benzoin. The main component in these natural products is benzoic acid. | https://www.wikidoc.org/index.php/Benzoin | |
33cc2bdac10cc729ee4392155ff30a9845c83795 | wikidoc | Berocca | Berocca
Berocca is a tablet containing a specific combination of B group vitamins and Vitamin C. Berocca is available in Argentina, Australia, Austria, Finland, France, Ireland, Malaysia, New Zealand, Philippines, Portugal, Russia, Singapore, South Africa, Spain, Sweden, Switzerland, Taiwan and the United Kingdom.
A product originally manufactured by Roche Pharmaceuticals, now manufactured by Bayer after Bayer's global acquisition of Roche Consumer Health in January 2005.
# Varieties
Berocca Original and Tropical are available in packs of 10, 15 and 30 effervescent tablets. Berocca Performance is available in packs of 15 and 30 effervescent tablets and also 30 regular (film-coated) tablets.
Berocca Performance is an enhanced formulation of B group vitamins, Vitamin C plus added magnesium, calcium and zinc.
# Ingredients
Ingredients in Berocca Original:
Citric acid, sodium hydrogen carbonate, vitamin C, magnesium sulphate, mannitol, calcium carbonate, magnesium carbonate,flavouring, colours (beetroot red, beta carotene), sodium carbonate, niacin, sweeteners (aspartame, acesulfame K), sodium chloride, zinc citrate, pantothenic acid, riboflavin, thiamin, vitamin B12, vitamin B6, anti-foaming agent (polysorbate 60), folacin (folic acid), biotin. Contains a source of phenylalanine.
## Active Ingredients
Active ingredients of Berocca Original and Tropical:
- Thiamine hydrochloride (Vit. B1) 15 mg
- Riboflavine (Vit. B2) 15 mg
- Nicotinamide (Vit. B3) 50 mg
- Pantothenic acid (Vit. B5) 23 mg
- Pyridoxine hydrochloride (Vit. B6) 10 mg
- Cyanocobalamin (Vit. B12) 10 mcg
- Ascorbic acid (Vit. C) 1000 mg
- Calcium 65 mg
Active ingredients of Berocca Performance:
- Thiamine hydrochloride (Vit. B1) 15 mg
- Riboflavine (Vit. B2) 15 mg
- Nicotinamide (Vit. B3) 50 mg
- Pantothenic acid (Vit. B5) 23 mg
- Pyridoxine hydrochloride (Vit. B6) 10 mg
- Cyanocobalamin (Vit. B12) 10 mcg
- Biotin (Vit. H)150 mcg
- Folic acid 400 mcg
- Ascorbic acid (Vit. C) 500 mg
- Calcium 100 mg
- Magnesium 100 mg
- Zinc 10 mg
# Uses
Berocca, taken before drinking alcohol, is anecdotally said to prevent hangovers. Similarly, it is anecdotally said to relieve hangovers. If taken in effervescent form, there will be a rehydrating effect. There is also some evidence that vitamin B helps relieve hangover symptoms. Its sweet, fizzy solution can be easier on the stomach than other vitamins such as those in tablet form.
# Additional information
All Berocca products are gluten and lactose free.
Berocca:
AUST L 57605 (original)
AUST L 57883 (tropical)
Berocca Performance:
AUST L 81974 (effervescent)
AUST L 82484 (film coated)
Berocca licence code in Finland:
Berocca: Vnr 559591
Berocca Drink: unknown
Berocca code in Malaysia:
MAL 05092248X
# Consumer Warnings
Recommended daily dose:
From age 11 to adult - one tablet daily.
Each Berocca tablet contains 285mg of sodium, which should be taken into account by those on a low sodium diet.
Always read the label. Use only as directed. See your doctor if symptoms persist.
# Advertisements
Well known in Australia for a series of television commercials throughout the 1980s and 1990s with the slogan "B-B-B-B-Berocca gives you back your B-B-Bounce".
A current marketing campaign in Australia for Berocca Performance with the slogan "Release the inner geek" targets students studying for final examinations.
In South Africa a "Beready Besharp Besomebody Berocca" campaign was also launched.
Long-running Outdoor (poster) campaigns in the UK with the slogan "Stay sharp".
# Awards
Boots Vitamin Award Winner (as voted by Boots customers) for Best Energy supplement 2004 | Berocca
Berocca is a tablet containing a specific combination of B group vitamins and Vitamin C. Berocca is available in Argentina, Australia, Austria, Finland, France, Ireland, Malaysia, New Zealand, Philippines, Portugal, Russia, Singapore, South Africa, Spain, Sweden, Switzerland, Taiwan and the United Kingdom.
A product originally manufactured by Roche Pharmaceuticals, now manufactured by Bayer after Bayer's global acquisition of Roche Consumer Health in January 2005.
# Varieties
Berocca Original and Tropical are available in packs of 10, 15 and 30 effervescent tablets. Berocca Performance is available in packs of 15 and 30 effervescent tablets and also 30 regular (film-coated) tablets.
Berocca Performance is an enhanced formulation of B group vitamins, Vitamin C plus added magnesium, calcium and zinc. [1]
# Ingredients
Ingredients in Berocca Original:
Citric acid, sodium hydrogen carbonate, vitamin C, magnesium sulphate, mannitol, calcium carbonate, magnesium carbonate,flavouring, colours (beetroot red, beta carotene), sodium carbonate, niacin, sweeteners (aspartame, acesulfame K), sodium chloride, zinc citrate, pantothenic acid, riboflavin, thiamin, vitamin B12, vitamin B6, anti-foaming agent (polysorbate 60), folacin (folic acid), biotin. Contains a source of phenylalanine.
## Active Ingredients
Active ingredients of Berocca Original and Tropical:
- Thiamine hydrochloride (Vit. B1) 15 mg
- Riboflavine (Vit. B2) 15 mg
- Nicotinamide (Vit. B3) 50 mg
- Pantothenic acid (Vit. B5) 23 mg
- Pyridoxine hydrochloride (Vit. B6) 10 mg
- Cyanocobalamin (Vit. B12) 10 mcg
- Ascorbic acid (Vit. C) 1000 mg
- Calcium 65 mg
Active ingredients of Berocca Performance:
- Thiamine hydrochloride (Vit. B1) 15 mg
- Riboflavine (Vit. B2) 15 mg
- Nicotinamide (Vit. B3) 50 mg
- Pantothenic acid (Vit. B5) 23 mg
- Pyridoxine hydrochloride (Vit. B6) 10 mg
- Cyanocobalamin (Vit. B12) 10 mcg
- Biotin (Vit. H)150 mcg
- Folic acid 400 mcg
- Ascorbic acid (Vit. C) 500 mg
- Calcium 100 mg
- Magnesium 100 mg
- Zinc 10 mg
# Uses
Berocca, taken before drinking alcohol, is anecdotally said to prevent hangovers. Similarly, it is anecdotally said to relieve hangovers. If taken in effervescent form, there will be a rehydrating effect. There is also some evidence that vitamin B helps relieve hangover symptoms. Its sweet, fizzy solution can be easier on the stomach than other vitamins such as those in tablet form.
# Additional information
All Berocca products are gluten and lactose free.
Berocca:
AUST L 57605 (original)
AUST L 57883 (tropical)
Berocca Performance:
AUST L 81974 (effervescent)
AUST L 82484 (film coated)
Berocca licence code in Finland:
Berocca: Vnr 559591
Berocca Drink: unknown
Berocca code in Malaysia:
MAL 05092248X
# Consumer Warnings
Recommended daily dose:
From age 11 to adult - one tablet daily.
Each Berocca tablet contains 285mg of sodium, which should be taken into account by those on a low sodium diet.
Always read the label. Use only as directed. See your doctor if symptoms persist.
# Advertisements
Well known in Australia for a series of television commercials throughout the 1980s and 1990s with the slogan "B-B-B-B-Berocca gives you back your B-B-Bounce".
A current marketing campaign in Australia for Berocca Performance with the slogan "Release the inner geek" targets students studying for final examinations.
In South Africa a "Beready Besharp Besomebody Berocca" campaign was also launched.
Long-running Outdoor (poster) campaigns in the UK with the slogan "Stay sharp".
# Awards
Boots Vitamin Award Winner (as voted by Boots customers) for Best Energy supplement 2004
# External links
- The Medical Journal Of Australia: Effectiveness of complementary and self-help treatments for anxiety disorders
- Berocca Finland
- Berocca Argentina
- Berocca South Africa
- Berocca Spain
- Berocca Sweden
- Berocca Switzerland
- Berocca UK
fi:Berocca | https://www.wikidoc.org/index.php/Berocca | |
0380bf2454eef101637235bfffd875024d322392 | wikidoc | Betaine | Betaine
# Disclaimer
WikiDoc MAKES NO GUARANTEE OF VALIDITY. WikiDoc is not a professional health care provider, nor is it a suitable replacement for a licensed healthcare provider. WikiDoc is intended to be an educational tool, not a tool for any form of healthcare delivery. The educational content on WikiDoc drug pages is based upon the FDA package insert, National Library of Medicine content and practice guidelines / consensus statements. WikiDoc does not promote the administration of any medication or device that is not consistent with its labeling. Please read our full disclaimer here.
# Overview
Betaine is a methylating agent that is FDA approved for the {{{indicationType}}} of homocystinuria due to cystathionine beta-synthase (CBS) deficiency, 5,10-methylenetetrahydrofolate reductase (MTHFR) deficiency, and cobalamin cofactor metabolism (cbl) defect. Common adverse reactions include nausea and gastrointestinal distress.
# Adult Indications and Dosage
## FDA-Labeled Indications and Dosage (Adult)
- The usual dosage in adult is 6 grams per day administered orally in divided doses of 3 grams twice daily.
- Therapy with Cystadane should be directed by physicians knowledgeable in the management of patients with homocystinuria. Patient response to Cystadane can be monitored by homocysteine plasma levels. Dosage in all patients can be gradually increased until plasma total homocysteine is undetectable or present only in small amounts. Response (by homocysteine plasma levels) usually occurs within several days and steady state within a month. Plasma methionine concentrations should be monitored in patients with CBS deficiency.
- Dosages of up to 20 grams per day have been necessary to control homocysteine levels in some patients. However, one pharmacokinetic and pharmacodynamic in vitro simulation study indicated minimal benefit from exceeding a twice-daily dosing schedule and a 150 mg/kg/day dosage for Cystadane.
## Off-Label Use and Dosage (Adult)
### Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Betaine in adult patients.
### Non–Guideline-Supported Use
- Oral betaine anhydrous solution 20 grams daily in two divided doses for 1 year.
# Pediatric Indications and Dosage
## FDA-Labeled Indications and Dosage (Pediatric)
- The usual dosage in pediatric patients is 6 grams per day administered orally in divided doses of 3 grams twice daily. In pediatric patients less than 3 years of age, dosage may be started at 100 mg/kg/day divided in twice daily doses, and then increased weekly by 50 mg/kg increments.
- Therapy with Cystadane should be directed by physicians knowledgeable in the management of patients with homocystinuria. Patient response to Cystadane can be monitored by homocysteine plasma levels. Dosage in all patients can be gradually increased until plasma total homocysteine is undetectable or present only in small amounts. Response (by homocysteine plasma levels) usually occurs within several days and steady state within a month. Plasma methionine concentrations should be monitored in patients with CBS deficiency.
- Dosages of up to 20 grams per day have been necessary to control homocysteine levels in some patients. However, one pharmacokinetic and pharmacodynamic in vitro simulation study indicated minimal benefit from exceeding a twice-daily dosing schedule and a 150 mg/kg/day dosage for Cystadane.
## Off-Label Use and Dosage (Pediatric)
### Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Betaine in pediatric patients.
### Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Betaine in pediatric patients.
# Contraindications
- None
# Warnings
### Precautions
- Hypermethioninemia
- Risk of Hypermethioninemia in Patients with CBS Deficiency
Patients with homocystinuria due to cystathionine beta-synthase (CBS) deficiency may also have elevated plasma methionine concentrations. Treatment with Cystadane may further increase methionine concentrations due to the remethylation of homocysteine to methionine. Cerebral edema has been reported in patients with hypermethioninemia, including patients treated with Cystadane. Plasma methionine concentrations should be monitored in patients with CBS deficiency. Plasma methionine concentrations should be kept below 1,000 µmol/L through dietary modification and, if necessary, a reduction of Cystadane dose.
- Patients with homocystinuria due to cystathionine beta-synthase (CBS) deficiency may also have elevated plasma methionine concentrations. Treatment with Cystadane may further increase methionine concentrations due to the remethylation of homocysteine to methionine. Cerebral edema has been reported in patients with hypermethioninemia, including patients treated with Cystadane. Plasma methionine concentrations should be monitored in patients with CBS deficiency. Plasma methionine concentrations should be kept below 1,000 µmol/L through dietary modification and, if necessary, a reduction of Cystadane dose.
# Adverse Reactions
## Clinical Trials Experience
- The most serious adverse reaction reported with Cystadane treatment is the development of hypermethioninemia and cerebral edema in patients with CBS Deficiency.
- The assessment of clinical adverse reactions is based on a survey study of 41 physicians, who treated a total of 111 homocystinuria patients with Cystadane. Adverse reactions were retrospectively recalled and were not collected systematically in this open-label, uncontrolled, physician survey. Thus, this list may not encompass all types of potential adverse reactions, reliably estimate their frequency, or establish a causal relationship to drug exposure. The following adverse reactions were reported (Table 1):
## Postmarketing Experience
- The following adverse reactions have been identified during post approval use of Cystadane. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
- In postmarketing experience with Cystadane, severe cerebral edema and hypermethioninemia have been reported within 2 weeks to 6 months of starting betaine therapy, with complete recovery after discontinuation of Cystadane. All patients who developed cerebral edema had homocystinuria due to CBS deficiency and had severe elevation in plasma methionine levels (range 1,000 to 3,000 µM). As cerebral edema has also been reported in patients with hypermethioninemia, secondary hypermethioninemia due to betaine therapy has been postulated as a possible mechanism of action.
- The following adverse reactions have been reported in patients during postmarketing use of Cystadane: anorexia, agitation, depression, irritability, personality disorder, sleep disturbed, dental disorders, diarrhea, glossitis, nausea, stomach discomfort, vomiting, hair loss, hives, skin odor abnormalities, and urinary incontinence.
# Drug Interactions
There is limited information regarding Betaine Drug Interactions in the drug label.
# Use in Specific Populations
### Pregnancy
Pregnancy Category (FDA):
- Pregnancy Category C
- Animal reproduction studies have not been conducted with Cystadane. It is also not known whether Cystadane can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Cystadane should be given to a pregnant woman only if clearly needed.
Pregnancy Category (AUS):
- Australian Drug Evaluation Committee (ADEC) Pregnancy Category
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Betaine in women who are pregnant.
### Labor and Delivery
There is no FDA guidance on use of Betaine during labor and delivery.
### Nursing Mothers
- It is not known whether Cystadane is excreted in human milk. Use only if clearly needed.
### Pediatric Use
- The majority of case studies of homocystinuria patients treated with Cystadane have been pediatric patients, including patients ranging in age from 24 days to 17 years. Children younger than 3 years of age may benefit from dose titration.
### Geriatic Use
There is no FDA guidance on the use of Betaine with respect to geriatric patients.
### Gender
There is no FDA guidance on the use of Betaine with respect to specific gender populations.
### Race
There is no FDA guidance on the use of Betaine with respect to specific racial populations.
### Renal Impairment
There is no FDA guidance on the use of Betaine in patients with renal impairment.
### Hepatic Impairment
There is no FDA guidance on the use of Betaine in patients with hepatic impairment.
### Females of Reproductive Potential and Males
There is no FDA guidance on the use of Betaine in women of reproductive potentials and males.
### Immunocompromised Patients
There is no FDA guidance one the use of Betaine in patients who are immunocompromised.
# Administration and Monitoring
### Administration
- Oral
### Monitoring
There is limited information regarding Monitoring of Betaine in the drug label.
# IV Compatibility
There is limited information regarding IV Compatibility of Betaine in the drug label.
# Overdosage
## Chronic Overdose
There is limited information regarding Chronic Overdose of Betaine in the drug label.
# Pharmacology
There is limited information regarding Betaine Pharmacology in the drug label.
## Mechanism of Action
- Cystadane acts as a methyl group donor in the remethylation of homocysteine to methionine in patients with homocystinuria. Cystadane occurs naturally in the body. It is a metabolite of choline and is present in small amounts in foods such as beets, spinach, cereals, and seafood.
## Structure
- Cystadane (betaine anhydrous for oral solution) is an agent for the treatment of homocystinuria. It contains no ingredients other than anhydrous betaine. Cystadane is a white, granular, hygroscopic powder, which is diluted in water and administered orally. The chemical name of betaine anhydrous powder is trimethylglycine. It has a molecular weight of 117.15. The structural formula is:
## Pharmacodynamics
- Cystadane was observed to lower plasma homocysteine levels in three types of homocystinuria, including CBS deficiency; MTHFR deficiency; and cbl defect. Patients have taken Cystadane for many years without evidence of tolerance. There has been no demonstrated correlation between Cystadane levels and homocysteine levels.
- In CBS-deficient patients, large increases in methionine levels over baseline have been observed. Cystadane has also been demonstrated to increase low plasma methionine and S-adenosylmethionine (SAM) levels in patients with MTHFR deficiency and cbl defect.
## Pharmacokinetics
- Pharmacokinetic studies of Cystadane are not available. Plasma levels of Cystadane have not been measured in patients and have not been correlated to homocysteine levels.
## Nonclinical Toxicology
- Long-term carcinogenicity and fertility studies have not been conducted with Cystadane. No evidence of genotoxicity was demonstrated in the following tests: metaphase analysis of human lymphocytes; bacterial reverse mutation assay; and mouse micronucleus test.
# Clinical Studies
- Cystadane was studied in a double-blind, placebo-controlled, crossover study in 6 patients with CBS deficiency, ages 7 to 32 years at enrollment. Cystadane was administered at a dosage of 3 grams twice daily, for 12 months. Plasma homocystine levels were significantly reduced (p<0.01) compared to placebo. Plasma methionine levels were variable and not significantly different compared to placebo. No adverse events were reported in any patient.
- Cystadane has also been evaluated in observational studies without concurrent controls in patients with homocystinuria due to CBS deficiency, MTHFR deficiency, or cbl defect.A review of 16 case studies and the randomized controlled trial previously described was also conducted, and the data available for each study were summarized; however, no formal statistical analyses were performed. The studies included a total of 78 male and female patients with homocystinuria who were treated with Cystadane. This included 48 patients with CBS deficiency, 13 with MTHFR deficiency, and 11 with cbl defect, ranging in age from 24 days to 53 years. The majority of patients (n=48) received 6 gm/day, 3 patients received less than 6 gm/day, 12 patients received doses from 6 to 15 gm/day, and 5 patients received doses over 15 gm/day. Most patients were treated for more than 3 months (n=57) and 30 patients were treated for 1 year or longer (range 1 month to 11 years). Homocystine is formed nonenzymatically from two molecules of homocysteine, and both have be used to evaluate the effect of Cystadane in patients with homocystinuria. Plasma homocystine or homocysteine levels were reported numerically for 62 patients, and 61 of these patients showed decreases with Cystadane treatment. Homocystine decreased by 83-88% regardless of pre-treatment level, and homocysteine decreased by 71-83%, regardless of the pre-treatment level. Clinical improvement, such as improvement in seizures, or behavioral and cognitive functioning, was reported by the treating physicians in about three-fourths of patients. Many of these patients were also taking other therapies such as vitamin B6 (pyridoxine), vitamin B12 (cobalamin), and folate with variable biochemical responses. In most cases, adding Cystadane resulted in a further reduction of either homocystine or homocysteine.
# How Supplied
- Cystadane is available in plastic bottles containing 180 grams of betaine anhydrous. Each bottle is equipped with a plastic child-resistant cap and is supplied with a polystyrene measuring scoop. One level scoop (1.7 mL) is equal to 1 gram of betaine anhydrous powder.
- NDC 66621-4000-1 180 g/bottle
- Cystadane can be ordered by calling AnovoRx Group, LLC, Customer service at 1-888-487-4703
- Storage
- Store at room temperature, 15 – 30 ˚C (59 – 86 ˚F). Protect from moisture.
## Storage
There is limited information regarding Betaine Storage in the drug label.
# Images
## Drug Images
## Package and Label Display Panel
# Patient Counseling Information
- Patients should be advised of the following information before beginning treatment with Cystadane:
- Dosing and Administration
- Instruct patients and caregivers that Cystadane should only be taken as directed by their healthcare professional.
- Instruct patients and caregivers to administer Cystadane as follows:
Shake bottle lightly before removing cap.
Measure with the scoop provided.
Measure the number of scoops as prescribed by their healthcare professional. One level scoop (1.7 mL) is equivalent to 1 gram of betaine anhydrous powder.
Mix powder with 4 to 6 ounces (120 to 180 mL) of water, juice, milk, or formula until completely dissolved, or mix with food, then ingest mixture immediately.
Always replace the cap tightly after using, and protect powder from moisture.
- Shake bottle lightly before removing cap.
- Measure with the scoop provided.
- Measure the number of scoops as prescribed by their healthcare professional. One level scoop (1.7 mL) is equivalent to 1 gram of betaine anhydrous powder.
- Mix powder with 4 to 6 ounces (120 to 180 mL) of water, juice, milk, or formula until completely dissolved, or mix with food, then ingest mixture immediately.
- Always replace the cap tightly after using, and protect powder from moisture.
# Precautions with Alcohol
- Alcohol-Betaine interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.
# Brand Names
- CYSTADANE®
# Look-Alike Drug Names
There is limited information regarding Betaine Look-Alike Drug Names in the drug label.
# Drug Shortage Status
# Price | Betaine
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Vignesh Ponnusamy, M.B.B.S. [2]
# Disclaimer
WikiDoc MAKES NO GUARANTEE OF VALIDITY. WikiDoc is not a professional health care provider, nor is it a suitable replacement for a licensed healthcare provider. WikiDoc is intended to be an educational tool, not a tool for any form of healthcare delivery. The educational content on WikiDoc drug pages is based upon the FDA package insert, National Library of Medicine content and practice guidelines / consensus statements. WikiDoc does not promote the administration of any medication or device that is not consistent with its labeling. Please read our full disclaimer here.
# Overview
Betaine is a methylating agent that is FDA approved for the {{{indicationType}}} of homocystinuria due to cystathionine beta-synthase (CBS) deficiency, 5,10-methylenetetrahydrofolate reductase (MTHFR) deficiency, and cobalamin cofactor metabolism (cbl) defect. Common adverse reactions include nausea and gastrointestinal distress.
# Adult Indications and Dosage
## FDA-Labeled Indications and Dosage (Adult)
- The usual dosage in adult is 6 grams per day administered orally in divided doses of 3 grams twice daily.
- Therapy with Cystadane should be directed by physicians knowledgeable in the management of patients with homocystinuria. Patient response to Cystadane can be monitored by homocysteine plasma levels. Dosage in all patients can be gradually increased until plasma total homocysteine is undetectable or present only in small amounts. Response (by homocysteine plasma levels) usually occurs within several days and steady state within a month. Plasma methionine concentrations should be monitored in patients with CBS deficiency.
- Dosages of up to 20 grams per day have been necessary to control homocysteine levels in some patients. However, one pharmacokinetic and pharmacodynamic in vitro simulation study indicated minimal benefit from exceeding a twice-daily dosing schedule and a 150 mg/kg/day dosage for Cystadane.
## Off-Label Use and Dosage (Adult)
### Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Betaine in adult patients.
### Non–Guideline-Supported Use
- Oral betaine anhydrous solution 20 grams daily in two divided doses for 1 year.[1]
# Pediatric Indications and Dosage
## FDA-Labeled Indications and Dosage (Pediatric)
- The usual dosage in pediatric patients is 6 grams per day administered orally in divided doses of 3 grams twice daily. In pediatric patients less than 3 years of age, dosage may be started at 100 mg/kg/day divided in twice daily doses, and then increased weekly by 50 mg/kg increments.
- Therapy with Cystadane should be directed by physicians knowledgeable in the management of patients with homocystinuria. Patient response to Cystadane can be monitored by homocysteine plasma levels. Dosage in all patients can be gradually increased until plasma total homocysteine is undetectable or present only in small amounts. Response (by homocysteine plasma levels) usually occurs within several days and steady state within a month. Plasma methionine concentrations should be monitored in patients with CBS deficiency.
- Dosages of up to 20 grams per day have been necessary to control homocysteine levels in some patients. However, one pharmacokinetic and pharmacodynamic in vitro simulation study indicated minimal benefit from exceeding a twice-daily dosing schedule and a 150 mg/kg/day dosage for Cystadane.
## Off-Label Use and Dosage (Pediatric)
### Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Betaine in pediatric patients.
### Non–Guideline-Supported Use
There is limited information regarding Off-Label Non–Guideline-Supported Use of Betaine in pediatric patients.
# Contraindications
- None
# Warnings
### Precautions
- Hypermethioninemia
- Risk of Hypermethioninemia in Patients with CBS Deficiency
Patients with homocystinuria due to cystathionine beta-synthase (CBS) deficiency may also have elevated plasma methionine concentrations. Treatment with Cystadane may further increase methionine concentrations due to the remethylation of homocysteine to methionine. Cerebral edema has been reported in patients with hypermethioninemia, including patients treated with Cystadane. Plasma methionine concentrations should be monitored in patients with CBS deficiency. Plasma methionine concentrations should be kept below 1,000 µmol/L through dietary modification and, if necessary, a reduction of Cystadane dose.
- Patients with homocystinuria due to cystathionine beta-synthase (CBS) deficiency may also have elevated plasma methionine concentrations. Treatment with Cystadane may further increase methionine concentrations due to the remethylation of homocysteine to methionine. Cerebral edema has been reported in patients with hypermethioninemia, including patients treated with Cystadane. Plasma methionine concentrations should be monitored in patients with CBS deficiency. Plasma methionine concentrations should be kept below 1,000 µmol/L through dietary modification and, if necessary, a reduction of Cystadane dose.
# Adverse Reactions
## Clinical Trials Experience
- The most serious adverse reaction reported with Cystadane treatment is the development of hypermethioninemia and cerebral edema in patients with CBS Deficiency.
- The assessment of clinical adverse reactions is based on a survey study of 41 physicians, who treated a total of 111 homocystinuria patients with Cystadane. Adverse reactions were retrospectively recalled and were not collected systematically in this open-label, uncontrolled, physician survey. Thus, this list may not encompass all types of potential adverse reactions, reliably estimate their frequency, or establish a causal relationship to drug exposure. The following adverse reactions were reported (Table 1):
## Postmarketing Experience
- The following adverse reactions have been identified during post approval use of Cystadane. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
- In postmarketing experience with Cystadane, severe cerebral edema and hypermethioninemia have been reported within 2 weeks to 6 months of starting betaine therapy, with complete recovery after discontinuation of Cystadane. All patients who developed cerebral edema had homocystinuria due to CBS deficiency and had severe elevation in plasma methionine levels (range 1,000 to 3,000 µM). As cerebral edema has also been reported in patients with hypermethioninemia, secondary hypermethioninemia due to betaine therapy has been postulated as a possible mechanism of action.
- The following adverse reactions have been reported in patients during postmarketing use of Cystadane: anorexia, agitation, depression, irritability, personality disorder, sleep disturbed, dental disorders, diarrhea, glossitis, nausea, stomach discomfort, vomiting, hair loss, hives, skin odor abnormalities, and urinary incontinence.
# Drug Interactions
There is limited information regarding Betaine Drug Interactions in the drug label.
# Use in Specific Populations
### Pregnancy
Pregnancy Category (FDA):
- Pregnancy Category C
- Animal reproduction studies have not been conducted with Cystadane. It is also not known whether Cystadane can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Cystadane should be given to a pregnant woman only if clearly needed.
Pregnancy Category (AUS):
- Australian Drug Evaluation Committee (ADEC) Pregnancy Category
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Betaine in women who are pregnant.
### Labor and Delivery
There is no FDA guidance on use of Betaine during labor and delivery.
### Nursing Mothers
- It is not known whether Cystadane is excreted in human milk. Use only if clearly needed.
### Pediatric Use
- The majority of case studies of homocystinuria patients treated with Cystadane have been pediatric patients, including patients ranging in age from 24 days to 17 years. Children younger than 3 years of age may benefit from dose titration.
### Geriatic Use
There is no FDA guidance on the use of Betaine with respect to geriatric patients.
### Gender
There is no FDA guidance on the use of Betaine with respect to specific gender populations.
### Race
There is no FDA guidance on the use of Betaine with respect to specific racial populations.
### Renal Impairment
There is no FDA guidance on the use of Betaine in patients with renal impairment.
### Hepatic Impairment
There is no FDA guidance on the use of Betaine in patients with hepatic impairment.
### Females of Reproductive Potential and Males
There is no FDA guidance on the use of Betaine in women of reproductive potentials and males.
### Immunocompromised Patients
There is no FDA guidance one the use of Betaine in patients who are immunocompromised.
# Administration and Monitoring
### Administration
- Oral
### Monitoring
There is limited information regarding Monitoring of Betaine in the drug label.
# IV Compatibility
There is limited information regarding IV Compatibility of Betaine in the drug label.
# Overdosage
## Chronic Overdose
There is limited information regarding Chronic Overdose of Betaine in the drug label.
# Pharmacology
There is limited information regarding Betaine Pharmacology in the drug label.
## Mechanism of Action
- Cystadane acts as a methyl group donor in the remethylation of homocysteine to methionine in patients with homocystinuria. Cystadane occurs naturally in the body. It is a metabolite of choline and is present in small amounts in foods such as beets, spinach, cereals, and seafood.
## Structure
- Cystadane (betaine anhydrous for oral solution) is an agent for the treatment of homocystinuria. It contains no ingredients other than anhydrous betaine. Cystadane is a white, granular, hygroscopic powder, which is diluted in water and administered orally. The chemical name of betaine anhydrous powder is trimethylglycine. It has a molecular weight of 117.15. The structural formula is:
## Pharmacodynamics
- Cystadane was observed to lower plasma homocysteine levels in three types of homocystinuria, including CBS deficiency; MTHFR deficiency; and cbl defect. Patients have taken Cystadane for many years without evidence of tolerance. There has been no demonstrated correlation between Cystadane levels and homocysteine levels.
- In CBS-deficient patients, large increases in methionine levels over baseline have been observed. Cystadane has also been demonstrated to increase low plasma methionine and S-adenosylmethionine (SAM) levels in patients with MTHFR deficiency and cbl defect.
## Pharmacokinetics
- Pharmacokinetic studies of Cystadane are not available. Plasma levels of Cystadane have not been measured in patients and have not been correlated to homocysteine levels.
## Nonclinical Toxicology
- Long-term carcinogenicity and fertility studies have not been conducted with Cystadane. No evidence of genotoxicity was demonstrated in the following tests: metaphase analysis of human lymphocytes; bacterial reverse mutation assay; and mouse micronucleus test.
# Clinical Studies
- Cystadane was studied in a double-blind, placebo-controlled, crossover study in 6 patients with CBS deficiency, ages 7 to 32 years at enrollment. Cystadane was administered at a dosage of 3 grams twice daily, for 12 months. Plasma homocystine levels were significantly reduced (p<0.01) compared to placebo. Plasma methionine levels were variable and not significantly different compared to placebo. No adverse events were reported in any patient.
- Cystadane has also been evaluated in observational studies without concurrent controls in patients with homocystinuria due to CBS deficiency, MTHFR deficiency, or cbl defect.A review of 16 case studies and the randomized controlled trial previously described was also conducted, and the data available for each study were summarized; however, no formal statistical analyses were performed. The studies included a total of 78 male and female patients with homocystinuria who were treated with Cystadane. This included 48 patients with CBS deficiency, 13 with MTHFR deficiency, and 11 with cbl defect, ranging in age from 24 days to 53 years. The majority of patients (n=48) received 6 gm/day, 3 patients received less than 6 gm/day, 12 patients received doses from 6 to 15 gm/day, and 5 patients received doses over 15 gm/day. Most patients were treated for more than 3 months (n=57) and 30 patients were treated for 1 year or longer (range 1 month to 11 years). Homocystine is formed nonenzymatically from two molecules of homocysteine, and both have be used to evaluate the effect of Cystadane in patients with homocystinuria. Plasma homocystine or homocysteine levels were reported numerically for 62 patients, and 61 of these patients showed decreases with Cystadane treatment. Homocystine decreased by 83-88% regardless of pre-treatment level, and homocysteine decreased by 71-83%, regardless of the pre-treatment level. Clinical improvement, such as improvement in seizures, or behavioral and cognitive functioning, was reported by the treating physicians in about three-fourths of patients. Many of these patients were also taking other therapies such as vitamin B6 (pyridoxine), vitamin B12 (cobalamin), and folate with variable biochemical responses. In most cases, adding Cystadane resulted in a further reduction of either homocystine or homocysteine.
# How Supplied
- Cystadane is available in plastic bottles containing 180 grams of betaine anhydrous. Each bottle is equipped with a plastic child-resistant cap and is supplied with a polystyrene measuring scoop. One level scoop (1.7 mL) is equal to 1 gram of betaine anhydrous powder.
- NDC 66621-4000-1 180 g/bottle
- Cystadane can be ordered by calling AnovoRx Group, LLC, Customer service at 1-888-487-4703
- Storage
- Store at room temperature, 15 – 30 ˚C (59 – 86 ˚F). Protect from moisture.
## Storage
There is limited information regarding Betaine Storage in the drug label.
# Images
## Drug Images
## Package and Label Display Panel
# Patient Counseling Information
- Patients should be advised of the following information before beginning treatment with Cystadane:
- Dosing and Administration
- Instruct patients and caregivers that Cystadane should only be taken as directed by their healthcare professional.
- Instruct patients and caregivers to administer Cystadane as follows:
Shake bottle lightly before removing cap.
Measure with the scoop provided.
Measure the number of scoops as prescribed by their healthcare professional. One level scoop (1.7 mL) is equivalent to 1 gram of betaine anhydrous powder.
Mix powder with 4 to 6 ounces (120 to 180 mL) of water, juice, milk, or formula until completely dissolved, or mix with food, then ingest mixture immediately.
Always replace the cap tightly after using, and protect powder from moisture.
- Shake bottle lightly before removing cap.
- Measure with the scoop provided.
- Measure the number of scoops as prescribed by their healthcare professional. One level scoop (1.7 mL) is equivalent to 1 gram of betaine anhydrous powder.
- Mix powder with 4 to 6 ounces (120 to 180 mL) of water, juice, milk, or formula until completely dissolved, or mix with food, then ingest mixture immediately.
- Always replace the cap tightly after using, and protect powder from moisture.
# Precautions with Alcohol
- Alcohol-Betaine interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.
# Brand Names
- CYSTADANE®[2]
# Look-Alike Drug Names
There is limited information regarding Betaine Look-Alike Drug Names in the drug label.
# Drug Shortage Status
# Price | https://www.wikidoc.org/index.php/Betaine | |
f22624fb1454792c372c8d5a7cef16c197cf61ad | wikidoc | Bill W. | Bill W.
William Griffith Wilson (26 November 1895 - 24 January 1971) (also known as Bill Wilson or Bill W.), was the co-founder of Alcoholics Anonymous (AA), a fellowship of self-help groups dedicated to helping alcoholics recover from their disease. According to the AA tradition of anonymity, Wilson was and still is commonly known as "Bill W." In 1934, in the course of his struggle with alcoholism, Wilson underwent a spiritual experience that gave him the strength to stop drinking. He then took his method to other alcoholics, starting with AA co-founder Dr. Bob Smith in 1935. Working with the members of a growing society of recovering alcoholics, Wilson developed the Twelve-step spiritual program and the basic organizational guidelines for AA known as the Twelve Traditions. In spite of his sobriety, success, and recognition, Wilson was a deeply troubled man who suffered from compulsive behaviour and frequent depressions. Wilson turned over leadership of AA to the service board in 1955, and for the remainder of his life was free to experiment with alternate cures. He took an interest in spiritualism, in niacin (vitamin B3) as a possible cure for alcoholism, and in LSD as a means of inducing spiritual change. Wilson died of lung diseases in 1971. His wife, Lois Wilson was the founder of Al-Anon, a group dedicated to helping the friends and relatives of alcoholics.
# Childhood
When Wilson was 10, his father left on a business trip that turned out to be a permanent absence, and his mother announced that she would be leaving the family to study Osteopathic medicine. Abandoned by their parents, Wilson and his sister were left in the care of their maternal grandparents. Wilson showed some talent and determination in his teen years. He designed and carved a working boomerang after dozens of failed efforts. He taught himself to play the violin by dogged persistence, pasting to the neck of the instrument a diagram of the notes. At school, after initial difficulties, he found success in sports. But he experienced a serious depression at the age of seventeen when his first love, Bertha Bamford, died from complications during surgery.
# Marriage, work, and addiction
Wilson met his future wife Lois Burnham, who was four years older than he, during the summer of 1913 while sailing on Vermont's Emerald Lake; two years later the couple became engaged. Wilson was called into the army in 1917. During military training in Massachusetts, the young officers were often invited to dinner by the locals, and Wilson had his first drink, a glass of beer, to little effect. A few weeks later at another dinner party, Wilson drank some Bronx cocktails, and felt at ease with the guests and liberated from his awkward shyness; "I had found the elixir of life," he wrote. "Even that first evening I got thoroughly drunk, and within the next time or two I passed out completely. But as everyone drank hard, not too much was made of that."
Bill and Lois were married on January 24, 1918, just before he left to join the war in Europe as a 2nd Lieutenant in the Coast Artillery. After an uneventful military service but much exposure to wine and beer, Wilson returned to live with his wife in New York, his dependence on alcohol now fully established. He failed to graduate from law school because he was too drunk to pick up his diploma. Wilson became a stock speculator and had success travelling the country with his wife, evaluating companies for potential investors. (During these trips Lois had a hidden agenda: she hoped the travel would keep Wilson from drinking.)
However, Bill's constant drinking made business impossible and ruined his reputation. As his drinking grew more serious, starting in 1933 he had to be committed to the Towns psychiatric hospital three times under the care of Dr. William D. Silkworth. Silkworth's theory was that alcoholism took the form of an allergy (the inability to stop drinking once started) and an obsession (to take the first drink). Wilson gained hope from Silkworth's assertion alcoholism was a medical condition rather than a moral failing, but even that knowledge could not help him. He was eventually told that he would either die from his alcoholism or have to be locked up permanently due to alcoholic insanity.
# Conversion and turning point
One day, an old drinking friend named Ebby Thacher phoned Wilson wanting to visit with him. Expecting to spend a day drinking and re-living old times, Wilson was instead shocked by Thacher's refusal to drink. "I've got religion," he said to explain his unexpected abstinence. Thatcher had been sober for several weeks under the guidance of the Oxford Group, an evangelical society that, among other pursuits, sought to help drunkards achieve sobriety .
Shortly after Ebby's visit, Bill was admitted to Towns Hospital to recover from another bout of drinking. According to Bill, while lying in bed depressed and despairing, he cried out, "I'll do anything! Anything at all! If there be a God, let Him show Himself!". He then had the sensation of a bright light, a feeling of ecstasy, and a new serenity. He never drank again for the remainder of his life. Bill described what happened to Dr. Silkworth, who told him not to discount this experience. Ebby visited Bill in hospital and walked him through some of the basic tenets of the Oxford Group. Upon his release from the hospital, Bill was told to seek out and bring the message of his recovery to others as Ebby had done for him.
# A new spiritual program for recovery
Wilson joined the Oxford Group and set out trying to help other alcoholics, but he had no success in helping anyone get sober. At this time, Wilson as also influenced by his contact with Carl Jung, and became convinced of the importance of having a spiritual experience strong enough to change a person completely. Wilson visited Dr. Silkworth, who told him to stop preaching and to try talk to alcoholics about the grave nature of their disease, about the allergy and the obsession, and about Wilson's personal experience with alcohol. It was not long before Wilson had his chance to try this new approach. In 1935 Wilson made a business trip to Akron, Ohio. The venture fell through, and in a state of gloom and frustration he was tempted to drink again. He decided that his only hope in remaining sober was to help another alcoholic. So instead of entering a nearby bar, Wilson entered a phone booth at his hotel and started calling the phone numbers on a church directory he saw there. He eventually got through to Henrietta Seiberling, who was a member of an Oxford Group circle that had been searching for a solution to Dr. Bob Smith's drinking problem. Henrietta arranged a meeting between the two men. Dr. Bob had been unable to stay sober on his own, so he was skeptical that Wilson would be able to help him, but he agreed to give Wilson fifteen minutes nevertheless. Fifteen minutes turned into four hours as Wilson told Dr. Bob of the solution he had found. Not long after, Dr. Bob had his last drink -- a beer to help steady his hand to perform surgery. The new approach had worked so well that Wilson and Dr. Bob decided to try it with another alcoholic.
## Birth of AA
The two men went to a hospital to talk to another alcoholic named Bill D. They used the same approach that Wilson had used on Dr. Bob. Bill D. sobered up and now there were three men carrying the new message of recovery. (Years later, this meeting was recognised as the first Alcoholics Anonymous meeting.) The three men then carried the message to another alcoholic, and so the fellowship began its growth. Wilson soon returned to New York and began to carry the message there. His efforts bore fruit and soon there was a second group in New York City.
## A manual of recovery
In 1938, after about 100 alcoholics in Akron and New York had sobered up, the fellowship decided that a book would be the best way to promote their program of recovery; Wilson was chosen as primary author. The book was written to carry the message as a face-to-face meeting, and included the list of suggested activities for spiritual growth called the Twelve Steps. The title "Alcoholics Anonymous" was selected for the book, and the movement took on the same name.
## Leadership of AA
After positive articles in Liberty magazine in 1939 and the Saturday Evening Post in 1941, AA began its rapid growth. But when Wilson and Lois made a cross-country trip to visit AA groups, they found a wide variety of practices and rules, such as groups with charismatic leaders and groups with no concerns for anonymity. Wilson began to form a vision for a purely democratic constitution that would allow no accumulation of money, power, or prestige within AA. Ten years later, these rules were published as the "Twelve Traditions." The AA general service conference of 1955 was a landmark event for Wilson in which he turned over the leadership of the maturing organisation to an elected board.
# Life After AA
In the final fifteen years of his life, Wilson experimented with various novel treatments for alcoholism such as niacin (vitamin B3). For a time he became involved in experiments with LSD as a means of inducing the spiritual change he saw as essential to a release from alcoholism. For Wilson, spiritualism (communicating with the spirits of the dead) was a life-long interest. One of his letters to his spiritual advisor, Fr. Ed Dowling, suggests that while Wilson was working on his text book of the twelve steps and traditions he felt that his spiritualist activities were helping him: "I have good help — of that I am certain. Both here and over there," — the 'over there' referring to the spirit world and in paraticular to a dead 15th century monk named Boniface.. AA historian Ernest Kurtz asserts that "... despite his conviction that he had evidence for the reality of 'the spiritual' and so — in his logic — of the actual existence of a 'higher Power,' Wilson chose not to share, much less to proclaim or to impose, this foundation for faith either with, to, or upon Alcoholics Anonymous." Wilson and his AA colleagues took pains to keep Wilson's unconventional spiritual activities away from AA and public scrutiny. During the last years of his life, Wilson ceased attending AA meetings on the grounds that he would always be asked to speak as the co-founder rather than as an alcoholic.
Wilson's life was continuously slowed by another compulsion that he had not been able to drop: smoking, which brought on emphysema and later pneumonia. He continued to smoke even while dependent on an oxygen tank in the late 1960s. During the last days of his life, his health fading, Wilson was visited by colleagues and friends who wanted to say goodbye. Wilson died of emphysema and pneumonia on 24 January 1971 en route to treatment in Miami, Florida.
Wilson bought a house called Stepping Stones on an 8-acre estate in Bedford Hills, New York in 1941 and lived there with his wife until he died. After his wife died in 1988, the house was opened for tours and is now on the National Register of Historic Places.
# Bill W.: the man and his legacy
Wilson was a man of many great strengths and just as great weaknesses. He loved being the center of attention, but after the AA principle of anonymity had become established he refused an honorary degree from Yale University and refused to allow his picture — even from the back — on the cover of Time. Wilson's persistence, his ability to take and use good ideas, and his entrepreneurial flair are revealed in his pioneering escape from an alcoholic 'death sentence', his central role in the development of a program of spiritual growth, and his leadership in creating and building AA, "an independent, entrepreneurial, maddeningly democratic, non-profit organization."
Unknown to most of the AA membership, Wilson received millions of dollars in royalties from sales of AA books. In 1940 Bill bought out his publishing partner, Hank P., for $200 — taking advantage of Hank's being on a slip, "completely broke and very shaky." In a few years the share for which Hank received $200 would have been worth millions.
Wilson was a man of many aspects: he never escaped from smoking and other compulsive behaviours, and he continued to play the violin throughout his life. He was an accomplished leader, yet he was plagued with depression.
Wilson is perhaps best known as a synthesist of ideas, the man who pulled together various threads of psychology, theology, and democracy into a workable and life-saving system. Aldous Huxley called him "the greatest social architect of our century," and Time magazine named Wilson to their "Time 100" list of The Most Important People of the 20th Century. According to Susan Cheever, Wilson's self description was a man who "because of his bitter experience, discovered, slowly and through a conversion experience, a system of behaviour and a series of actions that works for alcoholics who want to stop drinking."
John Sutherland, in a review of My Name is Bill, sums up Wilson's character as follows:
Despite his victory over drink, Wilson remained incurably addictive. He chain-smoked himself into terminal emphysema. Even on his deathbed, he puffed incorrigibly as he suffocated. Although he drank nothing for the last thirty-seven years of his life, he always craved the stuff. As he lay dying, and delirious, he repeatedly demanded whisky. ...
Despite his programme's insistence on "rigorous honesty", Bill W. lived a lie. He had innumerable affairs and a long-term mistress with whom he contemplated eloping to Ireland (the scandal would probably have destroyed Alcoholics Anonymous). Susan Cheever's final judgement is unblinking but forgiving: "Bill Wilson never held himself up as a model: he only hoped to help other people by sharing his own experience, strength and hope. He insisted again and again that he was just an ordinary man". An ordinary man who nonetheless did one extraordinary thing. | Bill W.
William Griffith Wilson (26 November 1895 - 24 January 1971) (also known as Bill Wilson or Bill W.), was the co-founder of Alcoholics Anonymous (AA), a fellowship of self-help groups dedicated to helping alcoholics recover from their disease. According to the AA tradition of anonymity,[1] Wilson was and still is commonly known as "Bill W." In 1934, in the course of his struggle with alcoholism, Wilson underwent a spiritual experience that gave him the strength to stop drinking. He then took his method to other alcoholics, starting with AA co-founder Dr. Bob Smith in 1935. Working with the members of a growing society of recovering alcoholics, Wilson developed the Twelve-step spiritual program and the basic organizational guidelines for AA known as the Twelve Traditions. In spite of his sobriety, success, and recognition, Wilson was a deeply troubled man who suffered from compulsive behaviour and frequent depressions. Wilson turned over leadership of AA to the service board in 1955, and for the remainder of his life was free to experiment with alternate cures. He took an interest in spiritualism, in niacin (vitamin B3) as a possible cure for alcoholism, and in LSD as a means of inducing spiritual change.[2] Wilson died of lung diseases in 1971. His wife, Lois Wilson was the founder of Al-Anon, a group dedicated to helping the friends and relatives of alcoholics.
# Childhood
When Wilson was 10, his father left on a business trip that turned out to be a permanent absence, and his mother announced that she would be leaving the family to study Osteopathic medicine. Abandoned by their parents, Wilson and his sister were left in the care of their maternal grandparents. Wilson showed some talent and determination in his teen years. He designed and carved a working boomerang after dozens of failed efforts. He taught himself to play the violin by dogged persistence, pasting to the neck of the instrument a diagram of the notes. At school, after initial difficulties, he found success in sports. But he experienced a serious depression at the age of seventeen when his first love, Bertha Bamford, died from complications during surgery.
# Marriage, work, and addiction
Wilson met his future wife Lois Burnham, who was four years older than he, during the summer of 1913 while sailing on Vermont's Emerald Lake; two years later the couple became engaged. Wilson was called into the army in 1917. During military training in Massachusetts, the young officers were often invited to dinner by the locals, and Wilson had his first drink, a glass of beer, to little effect. [3] A few weeks later at another dinner party, Wilson drank some Bronx cocktails, and felt at ease with the guests and liberated from his awkward shyness; "I had found the elixir of life," he wrote.[4] "Even that first evening I got thoroughly drunk, and within the next time or two I passed out completely. But as everyone drank hard, not too much was made of that."[5]
Bill and Lois were married on January 24, 1918, just before he left to join the war in Europe as a 2nd Lieutenant in the Coast Artillery[6]. After an uneventful military service but much exposure to wine and beer, Wilson returned to live with his wife in New York, his dependence on alcohol now fully established. He failed to graduate from law school because he was too drunk to pick up his diploma.[7] Wilson became a stock speculator and had success travelling the country with his wife, evaluating companies for potential investors. (During these trips Lois had a hidden agenda: she hoped the travel would keep Wilson from drinking.[8])
However, Bill's constant drinking made business impossible and ruined his reputation. As his drinking grew more serious, starting in 1933 he had to be committed to the Towns psychiatric hospital three times under the care of Dr. William D. Silkworth. Silkworth's theory was that alcoholism took the form of an allergy (the inability to stop drinking once started) and an obsession (to take the first drink). Wilson gained hope from Silkworth's assertion alcoholism was a medical condition rather than a moral failing, but even that knowledge could not help him. He was eventually told that he would either die from his alcoholism or have to be locked up permanently due to alcoholic insanity.
# Conversion and turning point
One day, an old drinking friend named Ebby Thacher phoned Wilson wanting to visit with him. Expecting to spend a day drinking and re-living old times, Wilson was instead shocked by Thacher's refusal to drink. "I've got religion," he said to explain his unexpected abstinence. Thatcher had been sober for several weeks under the guidance of the Oxford Group, an evangelical society that, among other pursuits, sought to help drunkards achieve sobriety[9] .
Shortly after Ebby's visit, Bill was admitted to Towns Hospital to recover from another bout of drinking. According to Bill, while lying in bed depressed and despairing, he cried out, "I'll do anything! Anything at all! If there be a God, let Him show Himself!".[10] He then had the sensation of a bright light, a feeling of ecstasy, and a new serenity. He never drank again for the remainder of his life. Bill described what happened to Dr. Silkworth, who told him not to discount this experience. Ebby visited Bill in hospital and walked him through some of the basic tenets of the Oxford Group. Upon his release from the hospital, Bill was told to seek out and bring the message of his recovery to others as Ebby had done for him.
# A new spiritual program for recovery
Wilson joined the Oxford Group and set out trying to help other alcoholics, but he had no success in helping anyone get sober. At this time, Wilson as also influenced by his contact with Carl Jung, and became convinced of the importance of having a spiritual experience strong enough to change a person completely[11]. Wilson visited Dr. Silkworth, who told him to stop preaching[12] and to try talk to alcoholics about the grave nature of their disease, about the allergy and the obsession, and about Wilson's personal experience with alcohol. It was not long before Wilson had his chance to try this new approach. In 1935 Wilson made a business trip to Akron, Ohio. The venture fell through, and in a state of gloom and frustration he was tempted to drink again. He decided that his only hope in remaining sober was to help another alcoholic. So instead of entering a nearby bar, Wilson entered a phone booth at his hotel and started calling the phone numbers on a church directory he saw there. He eventually got through to Henrietta Seiberling, who was a member of an Oxford Group circle that had been searching for a solution to Dr. Bob Smith's drinking problem. Henrietta arranged a meeting between the two men. Dr. Bob had been unable to stay sober on his own, so he was skeptical that Wilson would be able to help him, but he agreed to give Wilson fifteen minutes nevertheless. Fifteen minutes turned into four hours as Wilson told Dr. Bob of the solution he had found. Not long after, Dr. Bob had his last drink -- a beer to help steady his hand to perform surgery. The new approach had worked so well that Wilson and Dr. Bob decided to try it with another alcoholic.
## Birth of AA
The two men went to a hospital to talk to another alcoholic named Bill D. They used the same approach that Wilson had used on Dr. Bob. Bill D. sobered up and now there were three men carrying the new message of recovery. (Years later, this meeting was recognised as the first Alcoholics Anonymous meeting.) The three men then carried the message to another alcoholic, and so the fellowship began its growth. Wilson soon returned to New York and began to carry the message there. His efforts bore fruit and soon there was a second group in New York City.
## A manual of recovery
In 1938, after about 100 alcoholics in Akron and New York had sobered up, the fellowship decided that a book would be the best way to promote their program of recovery; Wilson was chosen as primary author. The book was written to carry the message as a face-to-face meeting, and included the list of suggested activities for spiritual growth called the Twelve Steps. The title "Alcoholics Anonymous" was selected for the book, and the movement took on the same name.
## Leadership of AA
After positive articles in Liberty magazine in 1939 and the Saturday Evening Post in 1941, AA began its rapid growth. But when Wilson and Lois made a cross-country trip to visit AA groups, they found a wide variety of practices and rules, such as groups with charismatic leaders and groups with no concerns for anonymity.[13] Wilson began to form a vision for a purely democratic constitution that would allow no accumulation of money, power, or prestige within AA. Ten years later, these rules were published as the "Twelve Traditions." The AA general service conference of 1955 was a landmark event for Wilson in which he turned over the leadership of the maturing organisation to an elected board.
# Life After AA
In the final fifteen years of his life, Wilson experimented with various novel treatments for alcoholism such as niacin (vitamin B3). For a time he became involved in experiments with LSD as a means of inducing the spiritual change he saw as essential to a release from alcoholism.[14] For Wilson, spiritualism (communicating with the spirits of the dead) was a life-long interest. One of his letters to his spiritual advisor, Fr. Ed Dowling, suggests that while Wilson was working on his text book of the twelve steps and traditions he felt that his spiritualist activities were helping him: "I have good help — of that I am certain. Both here and over there," — the 'over there' referring to the spirit world and in paraticular to a dead 15th century monk named Boniface..[15] AA historian Ernest Kurtz asserts that "... despite his conviction that he had evidence for the reality of 'the spiritual' and so — in his logic — of the actual existence of a 'higher Power,' Wilson chose not to share, much less to proclaim or to impose, this foundation for faith either with, to, or upon Alcoholics Anonymous."[16] Wilson and his AA colleagues took pains to keep Wilson's unconventional spiritual activities away from AA and public scrutiny.[17] During the last years of his life, Wilson ceased attending AA meetings on the grounds that he would always be asked to speak as the co-founder rather than as an alcoholic.[18]
Wilson's life was continuously slowed by another compulsion that he had not been able to drop: smoking, which brought on emphysema and later pneumonia. He continued to smoke even while dependent on an oxygen tank in the late 1960s.[19] During the last days of his life, his health fading, Wilson was visited by colleagues and friends who wanted to say goodbye. Wilson died of emphysema and pneumonia on 24 January 1971 en route to treatment in Miami, Florida.
Wilson bought a house called Stepping Stones on an 8-acre estate in Bedford Hills, New York in 1941 and lived there with his wife until he died. After his wife died in 1988, the house was opened for tours and is now on the National Register of Historic Places.[20]
# Bill W.: the man and his legacy
Wilson was a man of many great strengths and just as great weaknesses. He loved being the center of attention, but after the AA principle of anonymity had become established he refused an honorary degree from Yale University and refused to allow his picture — even from the back — on the cover of Time. Wilson's persistence, his ability to take and use good ideas, and his entrepreneurial flair[21] are revealed in his pioneering escape from an alcoholic 'death sentence', his central role in the development of a program of spiritual growth, and his leadership in creating and building AA, "an independent, entrepreneurial, maddeningly democratic, non-profit organization."[22]
Unknown to most of the AA membership, Wilson received millions of dollars in royalties from sales of AA books.[citation needed] In 1940 Bill bought out his publishing partner, Hank P., for $200 — taking advantage of Hank's being on a slip, "completely broke and very shaky." In a few years the share for which Hank received $200 would have been worth millions.[citation needed]
Wilson was a man of many aspects: he never escaped from smoking and other compulsive behaviours, and he continued to play the violin throughout his life[23]. He was an accomplished leader, yet he was plagued with depression.
Wilson is perhaps best known as a synthesist of ideas,[24] the man who pulled together various threads of psychology, theology, and democracy into a workable and life-saving system. Aldous Huxley called him "the greatest social architect of our century,"[25] and Time magazine named Wilson to their "Time 100" list of The Most Important People of the 20th Century. According to Susan Cheever, Wilson's self description was a man who "because of his bitter experience, discovered, slowly and through a conversion experience, a system of behaviour and a series of actions that works for alcoholics who want to stop drinking."
John Sutherland, in a review of My Name is Bill, sums up Wilson's character as follows:[26]
Despite his victory over drink, Wilson remained incurably addictive. He chain-smoked himself into terminal emphysema. Even on his deathbed, he puffed incorrigibly as he suffocated. Although he drank nothing for the last thirty-seven years of his life, he always craved the stuff. As he lay dying, and delirious, he repeatedly demanded whisky. ...
Despite his programme's insistence on "rigorous honesty", Bill W. lived a lie. He had innumerable affairs and a long-term mistress with whom he contemplated eloping to Ireland (the scandal would probably have destroyed Alcoholics Anonymous). Susan Cheever's final judgement is unblinking but forgiving: "Bill Wilson never held himself up as a model: he only hoped to help other people by sharing his own experience, strength and hope. He insisted again and again that he was just an ordinary man". An ordinary man who nonetheless did one extraordinary thing. | https://www.wikidoc.org/index.php/Bill_W. | |
f32694dba0b07c96a3131aa0f53656e624ea95d1 | wikidoc | BinCARD | BinCARD
Bcl10-interacting CARD protein, also known as BinCARD, is a protein that in humans is encoded by the C9orf89 gene on chromosome 9. BinCARD is a member of the death-domain superfamily and contains a caspase recruitment domain (CARD). This protein regulates apoptosis and the immune response by inhibiting Bcl10, thus implicating it in diseases stemming from Bcl10 dysfunction.
# Structure
BinCARD, as a CARD-containing protein, is a member of the death-domain superfamily, which shares a six—helix bundle. In humans, the protein has two alternatively spliced isoforms: BinCARD-1 and BinCARD-2. Both isoforms share identical sequences until residue 101, which include the CARD domain and exons 1 to 3. The longer isoform, BinCARD-1, has an extended exon 3, while the shorter BinCARD-2 has an extra transmembrane domain. The conserved CARD domain has three cysteines in its native form: Cys7, Cys77, and Cys63, of which Cys7 and Cys77 form a disulfide bond and Cys63 becomes a cysteine sulfenic acid when oxidized.
# Function
The BinCARD protein is a member of the death-domain superfamily, which is known for regulating apoptosis and the immune response. BinCARD is a negative regulator that binds to, and thus blocks the phosphorylation of, Bcl10, effectively inhibiting Bcl10 from activating the nuclear factor-κB (NF-κB). In particular, the BinCARD-1 isoform contains an extended C-terminal that has been observed to bind Bcl10, though it mostly localizes to the nucleus. The second isoform, BinCARD-2, is more abundantly expressed and localizes to both the ER and the mitochondria. This isoform is expected to contribute to apoptosis via redox processes, as its three modifiable cysteines can be oxidized by reactive oxygen species (ROS) to stimulate an innate immune response.
# Clinical significance
Mutations in BinCARD and other proteins containing CARD domains are linked to Bcl10-related diseases, including lymphoma of mucosa-associated lymphoid tissue. Bcl10 has been shown to induce apoptosis and to activate NF-kappaB. This protein is reported to interact with other CARD domain containing proteins including CARD9, 10, 11 and 14, which are thought to function as upstream regulators in NF-kappaB signaling. Accordingly, BinCARD protein has a pivotal role in regulating apoptotic functions.
Because of its important biological and physiological functions, apoptosis is pivotal in many clinical constituents.During a normal embryologic processes, or during cell injury (such as ischemia-reperfusion injury during heart attacks and strokes) or during developments and processes in cancer, an apoptotic cell undergoes structural changes including cell shrinkage, plasma membrane blebbing, nuclear condensation, and fragmentation of the DNA and nucleus. This is followed by fragmentation into apoptotic bodies that are quickly removed by phagocytes, thereby preventing an inflammatory response. It is a mode of cell death defined by characteristic morphological, biochemical and molecular changes. It was first described as a "shrinkage necrosis", and then this term was replaced by apoptosis to emphasize its role opposite mitosis in tissue kinetics. In later stages of apoptosis the entire cell becomes fragmented, forming a number of plasma membrane-bounded apoptotic bodies which contain nuclear and or cytoplasmic elements. The ultrastructural appearance of necrosis is quite different, the main features being mitochondrial swelling, plasma membrane breakdown and cellular disintegration. Apoptosis occurs in many physiological and pathological processes. It plays an important role during embryonal development as programmed cell death and accompanies a variety of normal involutional processes in which it serves as a mechanism to remove "unwanted" cells.
BinCARD has reportedly suppressed NF-kappa B activation induced by BCL10 hereby decreasing the amounts of phosphorylated Bcl10. Subsequently, mutations at the residue Leu17 or Leu65, which is highly conserved in CARD, abolished the inhibitory effects of BinCARD on both Bcl10-induced activation of NF-kappa B and phosphorylation of Bcl10. Further, expression of BinCARD inhibited Bcl10 phosphorylation induced by T cell activation signal. These results suggest that BinCARD interacts with Bcl10 to inhibit Bcl10-mediated activation of NF-kappa B and to suppress Bcl10 phosphorylation. Accordingly, these processes regulating apoptosis during clinical processes such as cancer and ischemia-reperfusion injury.
# Interactions
BinCARD has been shown to interact with:
- Bcl10 | BinCARD
Bcl10-interacting CARD protein, also known as BinCARD, is a protein that in humans is encoded by the C9orf89 gene on chromosome 9.[1][2] BinCARD is a member of the death-domain superfamily and contains a caspase recruitment domain (CARD).[3] This protein regulates apoptosis and the immune response by inhibiting Bcl10, thus implicating it in diseases stemming from Bcl10 dysfunction.[3][4]
# Structure
BinCARD, as a CARD-containing protein, is a member of the death-domain superfamily, which shares a six—helix bundle.[3] In humans, the protein has two alternatively spliced isoforms: BinCARD-1 and BinCARD-2. Both isoforms share identical sequences until residue 101, which include the CARD domain and exons 1 to 3. The longer isoform, BinCARD-1, has an extended exon 3, while the shorter BinCARD-2 has an extra transmembrane domain.[3] The conserved CARD domain has three cysteines in its native form: Cys7, Cys77, and Cys63, of which Cys7 and Cys77 form a disulfide bond and Cys63 becomes a cysteine sulfenic acid when oxidized.[3][4]
# Function
The BinCARD protein is a member of the death-domain superfamily, which is known for regulating apoptosis and the immune response.[3] BinCARD is a negative regulator that binds to, and thus blocks the phosphorylation of, Bcl10, effectively inhibiting Bcl10 from activating the nuclear factor-κB (NF-κB).[3][4] In particular, the BinCARD-1 isoform contains an extended C-terminal that has been observed to bind Bcl10, though it mostly localizes to the nucleus.[3][4] The second isoform, BinCARD-2, is more abundantly expressed and localizes to both the ER and the mitochondria. This isoform is expected to contribute to apoptosis via redox processes, as its three modifiable cysteines can be oxidized by reactive oxygen species (ROS) to stimulate an innate immune response.[4]
# Clinical significance
Mutations in BinCARD and other proteins containing CARD domains are linked to Bcl10-related diseases, including lymphoma of mucosa-associated lymphoid tissue.[4] Bcl10 has been shown to induce apoptosis and to activate NF-kappaB. This protein is reported to interact with other CARD domain containing proteins including CARD9, 10, 11 and 14, which are thought to function as upstream regulators in NF-kappaB signaling. Accordingly, BinCARD protein has a pivotal role in regulating apoptotic functions.
Because of its important biological and physiological functions, apoptosis is pivotal in many clinical constituents.During a normal embryologic processes, or during cell injury (such as ischemia-reperfusion injury during heart attacks and strokes) or during developments and processes in cancer, an apoptotic cell undergoes structural changes including cell shrinkage, plasma membrane blebbing, nuclear condensation, and fragmentation of the DNA and nucleus. This is followed by fragmentation into apoptotic bodies that are quickly removed by phagocytes, thereby preventing an inflammatory response.[5] It is a mode of cell death defined by characteristic morphological, biochemical and molecular changes. It was first described as a "shrinkage necrosis", and then this term was replaced by apoptosis to emphasize its role opposite mitosis in tissue kinetics. In later stages of apoptosis the entire cell becomes fragmented, forming a number of plasma membrane-bounded apoptotic bodies which contain nuclear and or cytoplasmic elements. The ultrastructural appearance of necrosis is quite different, the main features being mitochondrial swelling, plasma membrane breakdown and cellular disintegration. Apoptosis occurs in many physiological and pathological processes. It plays an important role during embryonal development as programmed cell death and accompanies a variety of normal involutional processes in which it serves as a mechanism to remove "unwanted" cells.
BinCARD has reportedly suppressed NF-kappa B activation induced by BCL10 hereby decreasing the amounts of phosphorylated Bcl10. Subsequently, mutations at the residue Leu17 or Leu65, which is highly conserved in CARD, abolished the inhibitory effects of BinCARD on both Bcl10-induced activation of NF-kappa B and phosphorylation of Bcl10. Further, expression of BinCARD inhibited Bcl10 phosphorylation induced by T cell activation signal. These results suggest that BinCARD interacts with Bcl10 to inhibit Bcl10-mediated activation of NF-kappa B and to suppress Bcl10 phosphorylation.[4] Accordingly, these processes regulating apoptosis during clinical processes such as cancer and ischemia-reperfusion injury.
# Interactions
BinCARD has been shown to interact with:
- Bcl10[4] | https://www.wikidoc.org/index.php/BinCARD | |
f495022bf35a829cade657f67b7ce752548af288 | wikidoc | Bin bag | Bin bag
== Template:Intro length
[[Media:
Plastic bags are a convenient and sanitary way of handling rubbish, and are widely used. Plastic rubbish bags are fairly lightweight and are particularly useful for messy or wet rubbish, as is commonly the case with food waste, and are also useful for wrapping up rubbish to minimize odor. Plastic bags are often used for lining litter or waste containers or bins. This serves to keep the container sanitary by avoiding container contact with the rubbish. After the bag in the container is filled with litter, the bag can be pulled out by its edges, closed, and tied with minimal contact with the waste matter.
Plastic bags for rubbish or litter are sold in a number of sizes at many other stores in packets or rolls of a few tens of bags. Wire twist ties are sometimes supplied for closing the bag once full. In the mid-1990s rubbish bags with draw strings for closure were introduced. Some bags have handles which may be tied, or holes through which the neck of the bag can be pulled. Most commonly, the rather soft, flexible plastic used to make rubbish bags is LDPE (Low Density Polyethylene) or, for strength, LLDPE (Linear Low Density Polyethylene). HDPE (High Density Polyethylene) is sometimes used. ==
Created in 1950, this invention can be attributed to Canadians Harry Wasylyk, Larry Hansen and Frank Plomp. In a recent special on CBC television, the green garbage bag ranked 36th among the top 50 Canadian inventions.
Plastic bags can be incinerated with their contents in appropriate facilities for waste-to-energy conversion. They are stable and benign in sanitary landfills.
# Biodegradable plastic bags
Some bags are made of biodegradable polythene film. These will decompose when exposed to air, sun, and moisture or submitted for composting. They do not readily decompose in a sealed landfill. They are also considered a possible contaminant to plastic recycling operations.
Oxo-biodegradable and other degradable plastic bags have certain useful applications when used as rubbish bags. Organic waste can be put into oxo-biodegradable plastic sacks and put straight into the composting plant, unopened, thus reducing smells, disease transmission by insects, and handling hazards. The resulting compost may be used by farmers and growers. Since oxo-biodegradable plastic (unlike the starch-based alternative) releases its carbon slowly, it produces high quality compost. Oxo-biodegradable plastic does not degrade quickly in low temperature "windrow" composting, but it is suitable for "in-vessel" composting at the higher temperatures required by new animal by-products regulations. Oxo-biodegradable plastics become peroxidised and embrittled, and behave like natural waste. It is bio-assimilated by the same bacteria and fungi, which transform the degraded plastic products to cell biomass, like lignocellulosic materials. Oxo-biodegradable plastic is designed to fragment by a process which includes both photo-oxidation and thermo-oxidation, so it can degrade in the dark. | Bin bag
== Template:Intro length
[[Media:
]]
Plastic bags are a convenient and sanitary way of handling rubbish, and are widely used. Plastic rubbish bags are fairly lightweight and are particularly useful for messy or wet rubbish, as is commonly the case with food waste, and are also useful for wrapping up rubbish to minimize odor. Plastic bags are often used for lining litter or waste containers or bins. This serves to keep the container sanitary by avoiding container contact with the rubbish. After the bag in the container is filled with litter, the bag can be pulled out by its edges, closed, and tied with minimal contact with the waste matter.
Plastic bags for rubbish or litter are sold in a number of sizes at many other stores in packets or rolls of a few tens of bags. Wire twist ties are sometimes supplied for closing the bag once full. In the mid-1990s rubbish bags with draw strings for closure were introduced. Some bags have handles which may be tied, or holes through which the neck of the bag can be pulled. Most commonly, the rather soft, flexible plastic used to make rubbish bags is LDPE (Low Density Polyethylene) or, for strength, LLDPE (Linear Low Density Polyethylene). HDPE (High Density Polyethylene) is sometimes used. ==
Created in 1950, this invention can be attributed to Canadians Harry Wasylyk, Larry Hansen and Frank Plomp. In a recent special on CBC television, the green garbage bag ranked 36th among the top 50 Canadian inventions.[1]
Plastic bags can be incinerated with their contents in appropriate facilities for waste-to-energy conversion. They are stable and benign in sanitary landfills.
## Biodegradable plastic bags
Some bags are made of biodegradable polythene film. These will decompose when exposed to air, sun, and moisture or submitted for composting. They do not readily decompose in a sealed landfill. They are also considered a possible contaminant to plastic recycling operations.
Oxo-biodegradable and other degradable plastic bags have certain useful applications when used as rubbish bags. Organic waste can be put into oxo-biodegradable plastic sacks and put straight into the composting plant, unopened, thus reducing smells, disease transmission by insects, and handling hazards. The resulting compost may be used by farmers and growers. Since oxo-biodegradable plastic (unlike the starch-based alternative) releases its carbon slowly, it produces high quality compost. Oxo-biodegradable plastic does not degrade quickly in low temperature "windrow" composting, but it is suitable for "in-vessel" composting at the higher temperatures required by new animal by-products regulations. Oxo-biodegradable plastics become peroxidised and embrittled, and behave like natural waste. It is bio-assimilated by the same bacteria and fungi, which transform the degraded plastic products to cell biomass, like lignocellulosic materials. Oxo-biodegradable plastic is designed to fragment by a process which includes both photo-oxidation and thermo-oxidation, so it can degrade in the dark. | https://www.wikidoc.org/index.php/Bin_bag | |
471a3b41e4ffcd57351acb4b803fc701f38fff4a | wikidoc | Species | Species
In biology, a species is one of the basic units of biological classification and a taxonomic rank. A species is often defined as a group of organisms capable of interbreeding and producing fertile offspring. While in many cases this definition is adequate, more precise or differing measures are often used, such as based on similarity of DNA or morphology. Presence of specific locally-adapted traits may further subdivide species into subspecies.
The commonly used names for plant and animal taxa sometimes correspond to species: for example, "lion," "walrus," and "Camphor tree," each refers to a species. In other cases common names do not: for example, "deer" refers to a family of 34 species, including Eld's Deer, Red Deer and Wapiti (Elk). The last two species were once considered a single species, illustrating how species boundaries may change with increased scientific knowledge.
Each species is placed within a single genus. This is a hypothesis that the species is more closely related to other species within its genus than to species of other genera. All species are given a binomial name consisting of the generic name and specific name (or specific epithet). For example, Pinus palustris (commonly known as the Longleaf Pine).
A usable definition of the word "species" and reliable methods of identifying particular species are essential for stating and testing biological theories and for measuring biodiversity. Traditionally, multiple examples of a proposed species must be studied for unifying characters before it can be regarded as a species. Extinct species known only from fossils are generally difficult to give precise taxonomic rankings to. A species which has been described scientifically can be referred to by its binomial names.
Nevertheless, as Charles Darwin remarked,
Because of the difficulties with both defining and tallying the total numbers of different species in the world, it is estimated that there are anywhere between 2 and 100 million different species.
# Binomial convention for naming species
In scientific classification, a species is assigned a two-part name, treated as Latin, although roots from any language can be used as well as names of locales or individuals. The genus is listed first (with its leading letter capitalized), followed by a second term: for example, gray wolves belong to the species Canis lupus, coyotes to Canis latrans, golden jackals to Canis aureus, etc., and all of those belong to the genus Canis (which also contains many other species). The name of the species is the whole binomial, not just the second term (which may be called specific name for animals).
The binomial naming convention, later formalized in the biological codes of nomenclature, was first used by Leonhart Fuchs and introduced as the standard by Carolus Linnaeus in his 1758 classical work Systema Naturae 10th edition. As a result, it is sometimes called the "binomial nomenclature." At that time, the chief biological theory was that species represented independent acts of creation by God and were therefore considered objectively real and immutable.
## Abbreviation
Books and articles sometimes intentionally do not identify species fully and use the abbreviation "sp." in the singular or "spp." in the plural in place of the specific epithet: for example, Canis sp. This commonly occurs in the following types of situation:
- The authors are confident that some individuals belong to a particular genus but are not sure to which exact species they belong. This is particularly common in paleontology.
- The authors use "spp." as a short way of saying that something applies to many species within a genus, but do not wish to say that it applies to all species within that genus. If scientists mean that something applies to all species with a genus, they use the genus name without the specific epithet.
In books and articles that use the Latin alphabet, genus and species names are usually printed in italics. If using "sp." and "spp.," these should not be italicized.
# Difficulty of defining "species" and identifying particular species
It is surprisingly difficult to define the word "species" in a way that applies to all naturally occurring organisms, and the debate among biologists about how to define "species" and how to identify actual species is called the species problem.
Most textbooks define a species as all the individual organisms of a natural population that generally interbreed at maturity in the wild and whose interbreeding produces fertile offspring. Various parts of this definition are there to exclude some unusual or artificial matings:
- Those which occur only in captivity (when the animal's normal mating partners may not be available) or as a result of deliberate human action.
- Animals which may be physically and physiologically capable of mating but do not normally do so in the wild, for whatever reason.
- Animals whose offspring are normally sterile. For example, mules and hinnies have never (so far) produced further offspring when mated with a creature of the same type (a mule with a mule, or a hinny with a hinny).
## Living organisms
The typical textbook definition (above) works well for most multi-celled organisms, but there are several types of situations in which it breaks down:
- By definition it applies only to organisms which reproduce sexually. So it does not work for asexually reproducing single-celled organisms and for the relatively few parthenogenetic multi-celled organisms. The term "phylotype" is often applied to such organisms.
- Some hybrids, e.g., mules, hinnies, ligers and tigons, apparently cannot produce offspring when mated with one of their own kind (e.g. a mule with a mule), but sometimes do produce offspring when mated with members of one of the parent species (e.g. a liger with a lion). Usually in such hybrids the males are sterile, so one could improve the basic textbook definition by changing "... whose interbreeding produces fertile offspring" to "... whose interbreeding produces offspring in which both sexes are normally fertile".
- In ring species, members of adjacent populations interbreed successfully but members of widely-separated populations do not.
- In a few cases it may be physically impossible for animals which are members of the same species to mate, for example a Great Dane and a Chihuahua are both dogs and therefore members of the same species, but cannot mate because of the great difference in size and weight (physical build).
Horizontal gene transfer makes it even more difficult to define the word "species". There is strong evidence of horizontal gene transfer between very dissimilar groups of procaryotes, and possibly between dissimilar groups of single-celled eucaryotes; and Williamson argues that there is evidence for it in some crustaceans and echinoderms. All definitions of the word "species" assume that an organism gets all its genes from one or two parents which are very like that organism, but horizontal gene transfer makes that assumption false.
## Extinct organisms
Many extinct organisms are known only from fossils, which generally only preserve hard features. Fossils have not (so far) shown us what bred with what, and cannot tell us whether any resulting offspring would have been fertile. So paleontologists generally use either the morphological or the evolutionary definition of species (see below).
Paleontologists also have to cope with another difficulty: one species may gradually evolve into one or more others after a few million years; the original type of organism and the final one are so different that one could not regard the ancestors and the descendants as members of the same species if they existed at the same time; but the intermediate types are so similar to the next and previous types that one cannot say exactly where species A changed into species B. Paleontologists devised the concept of chronospecies to describe the simplest case, where at the end of the process there is only one descendant type of organism and there are no longer any individuals of the ancestral type. But even this refinement does not work in cases where several descendant types are alive at the same time or where the ancestral type and at least one descendant type are alive at the same time - and both of these situations are common in the evolution of life on Earth. Human evolution may offer a striking example: some geneticists have suggested that for about 1 million years there was some interbreeding between the early ancestors of humans and the early ancestors of chimpanzees (James Mallet and other MIT and Harvard scientists, as quoted in the news magazine This Week, June 9, 2006).
# Definitions of species
The question of how best to define "species" is one that has occupied biologists for centuries, and the debate itself has become known as the species problem. One definition that is widely used is that a species is a group of actually or potentially interbreeding populations that are reproductively isolated from other such groups.
The definition of a species given above is derived from the behavioral biologist Ernst Mayr, and is somewhat unrealistic. Since it assumes sexual reproduction, it leaves the term undefined for a large class of organisms that reproduce asexually. Biologists frequently do not know whether two morphologically similar groups of organisms are "potentially" capable of interbreeding. Further, there is considerable variation in the degree to which hybridization may succeed under natural and experimental conditions, or even in the degree to which some organisms use sexual reproduction between individuals to breed. Consequently, several lines of thought in the definition of species exist:
In practice, these definitions often coincide, and the differences between them are more a matter of emphasis than of outright contradiction. Nevertheless, no species concept yet proposed is entirely objective, or can be applied in all cases without resorting to judgment. Given the complexity of life, some have argued that such an objective definition is in all likelihood impossible, and biologists should settle for the most practical definition. For most vertebrates, this is the biological species concept (BSC), and to a lesser extent (or for different purposes) the phylogenetic species concept (PSC). Many BSC subspecies are considered species under the PSC; the difference between the BSC and the PSC can be summed up insofar as that the BSC defines a species as a consequence of manifest evolutionary history, while the PSC defines a species as a consequence of manifest evolutionary potential. Thus, a PSC species is "made" as soon as an evolutionary lineage has started to separate, while a BSC species starts to exist only when the lineage separation is complete. Accordingly, there can be considerable conflict between alternative classifications based upon the PSC versus BSC, as they differ completely in their treatment of taxa that would be considered subspecies under the latter model (e.g., the numerous subspecies of honey bees).
# Importance in biological classification
The idea of species has a long history. It is one of the most important levels of classification, for several reasons:
- It often corresponds to what lay people treat as the different basic kinds of organism - dogs are one species, cats another.
- It is the standard binomial nomenclature (or trinomial nomenclature) by which scientists typically refer to organisms.
- It is the highest taxonomic level which mostly cannot be made more or less inclusionary.
After thousands of years of use, the concept remains central to biology and a host of related fields, and yet also remains at times ill-defined.
# Implications of assignment of species status
The naming of a particular species should be regarded as a hypothesis about the evolutionary relationships and distinguishability of that group of organisms. As further information comes to hand, the hypothesis may be confirmed or refuted. Sometimes, especially in the past when communication was more difficult, taxonomists working in isolation have given two distinct names to individual organisms later identified as the same species. When two named species are discovered to be of the same species, the older species name is usually retained, and the newer species name dropped, a process called synonymization, or convivially, as lumping. Dividing a taxon into multiple, often new, taxons is called splitting. Taxonomists are often referred to as "lumpers" or "splitters" by their colleagues, depending on their personal approach to recognizing differences or commonalities between organisms (see lumpers and splitters).
Traditionally, researchers relied on observations of anatomical differences, and on observations of whether different populations were able to interbreed successfully, to distinguish species; both anatomy and breeding behavior are still important to assigning species status. As a result of the revolutionary (and still ongoing) advance in microbiological research techniques, including DNA analysis, in the last few decades, a great deal of additional knowledge about the differences and similarities between species has become available. Many populations which were formerly regarded as separate species are now considered to be a single taxon, and many formerly grouped populations have been split. Any taxonomic level (species, genus, family, etc.) can be synonymized or split, and at higher taxonomic levels, these revisions have been still more profound.
From a taxonomical point of view, groups within a species can be defined as being of a taxon hierarchically lower than a species. In zoology only the subspecies is used, while in botany the variety, subvariety, and form are used as well. In conservation biology, the concept of evolutionary significant units (ESU) is used, which may be define either species or smaller distinct population segments.
# The isolation species concept in more detail
In general, for large, complex, organisms that reproduce sexually (such as mammals and birds), one of several variations on the isolation or biological species concept is employed. Often, the distinction between different species, even quite closely related ones, is simple. Horses (Equus caballus) and donkeys (Equus asinus) are easily told apart even without study or training, and yet are so closely related that they can interbreed after a fashion. Because the result, a mule or hinny, is not fertile, they are clearly separate species.
But many cases are more difficult to decide. This is where the isolation species concept diverges from the evolutionary species concept. Both agree that a species is a lineage that maintains its integrity over time, that is diagnosably different from other lineages (else we could not recognise it), is reproductively isolated (else the lineage would merge into others, given the chance to do so), and has a working intra-species recognition system (without which it could not continue). In practice, both also agree that a species must have its own independent evolutionary history—otherwise the characteristics just mentioned would not apply. The species concepts differ in that the evolutionary species concept does not make predictions about the future of the population: it simply records that which is already known. In contrast, the isolation species concept refuses to assign the rank of species to populations that, in the best judgement of the researcher, would recombine with other populations if given the chance to do so.
## The isolation question
There are, essentially, two questions to resolve. First, is the proposed species consistently and reliably distinguishable from other species? Second, is it likely to remain so in the future? To take the second question first, there are several broad geographic possibilities.
- The proposed species are sympatric—they occupy the same habitat. Observation of many species over the years has failed to establish even a single instance of two diagnostically different populations that exist in sympatry and have then merged to form one united population. Without reproductive isolation, population differences cannot develop, and given reproductive isolation, gene flow between the populations cannot merge the differences. This is not to say that cross breeding does not take place at all, simply that it has become negligible. Generally, the hybrid individuals are less capable of successful breeding than pure-bred individuals of either species.
- The proposed species are allopatric—they occupy different geographical areas. Obviously, it is not possible to observe reproductive isolation in allopatric groups directly. Often it is not possible to achieve certainty by experimental means either: even if the two proposed species interbreed in captivity, this does not demonstrate that they would freely interbreed in the wild, nor does it always provide much information about the evolutionary fitness of hybrid individuals. A certain amount can be inferred from other experimental methods: for example, do the members of population A respond appropriately to playback of the recorded mating calls of population B? Sometimes, experiments can provide firm answers. For example, there are seven pairs of apparently almost identical marine snapping shrimp (Alpheus) populations on either side of the Isthmus of Panama, which did not exist until about 3 million years ago. Until then, it is assumed, they were members of the same seven species. But when males and females from opposite sides of the isthmus are placed together, they fight instead of mating. Even if the isthmus were to sink under the waves again, the populations would remain genetically isolated: therefore they are now different species. In many cases, however, neither observation nor experiment can produce certain answers, and the determination of species rank must be made on a 'best guess' basis from a general knowledge of other related organisms.
- The proposed species are parapatric—they have breeding ranges that abut but do not overlap. This is fairly rare, particularly in temperate regions. The dividing line is often a sudden change in habitat (an ecotone) like the edge of a forest or the snow line on a mountain, but can sometimes be remarkably trivial. The parapatry itself indicates that the two populations occupy such similar ecological roles that they cannot coexist in the same area. Because they do not crossbreed, it is safe to assume that there is a mechanism, often behavioral, that is preventing gene flow between the populations, and that therefore they should be classified as separate species.
- There is a hybrid zone where the two populations mix. Typically, the hybrid zone will include representatives of one or both of the 'pure' populations, plus first-generation and back-crossing hybrids. The strength of the barrier to genetic transmission between the two pure groups can be assessed by the width of the hybrid zone relative to the typical dispersal distance of the organisms in question. The dispersal distance of oaks, for example, is the distance that a bird or squirrel can be expected to carry an acorn; the dispersal distance of Numbats is about 15 kilometres, as this is as far as young Numbats will normally travel in search of vacant territory to occupy after leaving the nest. The narrower the hybrid zone relative to the dispersal distance, the less gene flow there is between the population groups, and the more likely it is that they will continue on separate evolutionary paths. Nevertheless, it can be very difficult to predict the future course of a hybrid zone; the decision to define the two hybridizing populations as either the same species or as separate species is difficult and potentially controversial.
- The variation in the population is clinal; at either extreme of the population's geographic distribution, typical individuals are clearly different, but the transition between them is seamless and gradual. For example, the Koalas of northern Australia are clearly smaller and lighter in colour than those of the south, but there is no particular dividing line: the further south an individual Koala is found, the larger and darker it is likely to be; Koalas in intermediate regions are intermediate in weight and colour. In contrast, over the same geographic range, black-backed (northern) and white-backed (southern) Australian Magpies do not blend from one type to another: northern populations have black backs, southern populations white backs, and there is an extensive hybrid zone where both 'pure' types are common, as are crossbreeds. The variation in Koalas is clinal (a smooth transition from north to south, with populations in any given small area having a uniform appearance), but the variation in magpies is not clinal. In both cases, there is some uncertainty regarding correct classification, but the consensus view is that species rank is not justified in either. The gene flow between northern and southern magpie populations is judged to be sufficiently restricted to justify terming them subspecies (not full species); but the seamless way that local Koala populations blend one into another shows that there is substantial gene flow between north and south. As a result, experts tend to reject even subspecies rank in this case.
## The difference question
Obviously, when defining a species, the geographic circumstances become meaningful only if the populations groups in question are clearly different: if they are not consistently and reliably distinguishable from one another, then we have no grounds for believing that they might be different species. The key question in this context, is "how different is different?" and the answer is usually "it all depends".
In theory, it would be possible to recognise even the tiniest of differences as sufficient to delineate a separate species, provided only that the difference is clear and consistent (and that other criteria are met). There is no universal rule to state the smallest allowable difference between two species, but in general, very trivial differences are ignored on the twin grounds of simple practicality, and genetic similarity: if two population groups are so close that the distinction between them rests on an obscure and microscopic difference in morphology, or a single base substitution in a DNA sequence, then a demonstration of restricted gene flow between the populations will probably be difficult in any case.
More typically, one or other of the following requirements must be met:
- It is possible to reliably measure a quantitative difference between the two groups that does not overlap. A population has, for example, thicker fur, rougher bark, longer ears, or larger seeds than another population, and although this characteristic may vary within each population, the two do not grade into one another, and given a reasonably large sample size, there is a definite discontinuity between them. Note that this applies to populations, not individual organisms, and that a small number of exceptional individuals within a population may 'break the rule' without invalidating it. The less a quantitative difference varies within a population and the more it varies between populations, the better the case for making a distinction. Nevertheless, borderline situations can only be resolved by making a 'best-guess' judgement.
- It is possible to distinguish a qualitative difference between the populations; a feature that does not vary continuously but is either entirely present or entirely absent. This might be a distinctively shaped seed pod, an extra primary feather, a particular courting behaviour, or a clearly different DNA sequence.
Sometimes it is not possible to isolate a single difference between species, and several factors must be taken in combination. This is often the case with plants in particular. In eucalypts, for example, Corymbia ficifolia cannot be reliably distinguished from its close relative Corymbia calophylla by any single measure (and sometimes individual trees cannot be definitely assigned to either species), but populations of Corymbia can be clearly told apart by comparing the colour of flowers, bark, and buds, number of flowers for a given size of tree, and the shape of the leaves and fruit.
When using a combination of characteristics to distinguish between populations, it is necessary to use a reasonably small number of factors (if more than a handful are needed, the genetic difference between the populations is likely to be insignificant and is unlikely to endure into the future), and to choose factors that are functionally independent (height and weight, for example, should usually be considered as one factor, not two).
# Historical development of the species concept
In the earliest works of science, a species was simply an individual organism that represented a group of similar or nearly identical organisms. No other relationships beyond that group were implied. Aristotle used the words genus and species to mean generic and specific categories. Aristotle and other pre-Darwinian scientists took the species to be distinct and unchanging, with an "essence", like the chemical elements. When early observers began to develop systems of organization for living things, they began to place formerly isolated species into a context. Many of these early delineation schemes would now be considered whimsical and these included consanguinity based on color (all plants with yellow flowers) or behavior (snakes, scorpions and certain biting ants).
In the 18th century Carolus Linnaeus classified organisms according to differences in the form of reproductive apparatus. Although his system of classification sorts organisms according to degrees of similarity, it made no claims about the relationship between similar species. At that time, it was still widely believed that there was no organic connection between species, no matter how similar they appeared. This approach also suggested a type of idealism: the notion that each species existed as an "ideal form". Although there are always differences (although sometimes minute) between individual organisms, Linnaeus considered such variation problematic. He strove to identify individual organisms that were exemplary of the species, and considered other non-exemplary organisms to be deviant and imperfect.
By the 19th century most naturalists understood that species could change form over time, and that the history of the planet provided enough time for major changes. Jean-Baptiste Lamarck, in his 1809 Zoological Philosophy, offered one of the first logical arguments against creationism. The new emphasis was on determining how a species could change over time. Lamarck suggested that an organism could pass on an acquired trait to its offspring, i.e., the giraffe's long neck was attributed to generations of giraffes stretching to reach the leaves of higher treetops (this well-known and simplistic example, however, does not do justice to the breadth and subtlety of Lamarck's ideas). With the acceptance of the natural selection idea of Charles Darwin in the 1860s, however, Lamarck's view of goal-oriented evolution, also known as a teleological process, was eclipsed. Recent interest in inheritance of acquired characteristics centers around epigenetic processes, e.g. methylation, that do not affect DNA sequences, but instead alter expression in an inheritable manner. Thus, neo-lamarckism, as it is sometimes termed, is not a challenge to the theory of evolution by natural selection.
Charles Darwin and Alfred Wallace provided what scientists now consider as the most powerful and compelling theory of evolution. Darwin argued that it was populations that evolved, not individuals. His argument relied on a radical shift in perspective from that of Linnaeus: rather than defining species in ideal terms (and searching for an ideal representative and rejecting deviations), Darwin considered variation among individuals to be natural. He further argued that variation, far from being problematic, actually provides the explanation for the existence of distinct species.
Darwin's work drew on Thomas Malthus' insight that the rate of growth of a biological population will always outpace the rate of growth of the resources in the environment, such as the food supply. As a result, Darwin argued, not all the members of a population will be able to survive and reproduce. Those that did will, on average, be the ones possessing variations—however slight—that make them slightly better adapted to the environment. If these variable traits are heritable, then the offspring of the survivors will also possess them. Thus, over many generations, adaptive variations will accumulate in the population, while counter-adaptive will be eliminated.
It should be emphasized that whether a variation is adaptive or non-adaptive depends on the environment: different environments favor different traits. Since the environment effectively selects which organisms live to reproduce, it is the environment (the "fight for existence") that selects the traits to be passed on. This is the theory of evolution by natural selection. In this model, the length of a giraffe's neck would be explained by positing that proto-giraffes with longer necks would have had a significant reproductive advantage to those with shorter necks. Over many generations, the entire population would be a species of long-necked animals.
In 1859, when Darwin published his theory of natural selection, the mechanism behind the inheritance of individual traits was unknown. Although Darwin made some speculations on how traits are inherited (pangenesis), his theory relies only on the fact that inheritable traits exist, and are variable (which makes his accomplishment even more remarkable.) Although Gregor Mendel's paper on genetics was published in 1866, its significance was not recognized. It was not until 1900 that his work was rediscovered by Hugo de Vries, Carl Correns and Erich von Tschermak, who realised that the "inheritable traits" in Darwin's theory are genes.
The theory of the evolution of species through natural selection has two important implications for discussions of species -- consequences that fundamentally challenge the assumptions behind Linnaeus' taxonomy. First, it suggests that species are not just similar, they may actually be related. Some students of Darwin argue that all species are descended from a common ancestor. Second, it supposes that "species" are not homogeneous, fixed, permanent things; members of a species are all different, and over time species change. This suggests that species do not have any clear boundaries but are rather momentary statistical effects of constantly changing gene-frequencies. One may still use Linnaeus' taxonomy to identify individual plants and animals, but one can no longer think of species as independent and immutable.
The rise of a new species from a parental line is called speciation. There is no clear line demarcating the ancestral species from the descendant species.
Although the current scientific understanding of species suggests that there is no rigorous and comprehensive way to distinguish between different species in all cases, biologists continue to seek concrete ways to operationalize the idea. One of the most popular biological definitions of species is in terms of reproductive isolation; if two creatures cannot reproduce to produce fertile offspring, then they are in different species. This definition captures a number of intuitive species boundaries, but it remains imperfect. It has nothing to say about species that reproduce asexually, for example, and it is very difficult to apply to extinct species. Moreover, boundaries between species are often fuzzy: there are examples where members of one population can produce fertile offspring with a second population, and members of the second population can produce fertile offspring with members of a third population, but members of the first and third population cannot produces fertile offspring. Consequently, some people reject this definition of a species.
Richard Dawkins defines two organisms as conspecific if and only if they have the same number of chromosomes and, for each chromosome, both organisms have the same number of nucleotides (The Blind Watchmaker, p. 118). However, most if not all taxonomists would strongly disagree. For example, in many amphibians, most notably in New Zealand's Leiopelma frogs, the genome consists of "core" chromosomes which are mostly invariable and accessory chromosomes, of which exist a number of possible combinations. Even though the chromosome numbers are highly variable between populations, these can interbreed successfully and form a single evolutionary unit. In plants, polyploidy is extremely commonplace with few restrictions on interbreeding; as individuals with an odd number of chromosome sets are usually sterile, depending on the actual number of chromosome sets present, this results in the odd situation where some individuals of the same evolutionary unit can interbreed with certain others and some cannot, with all populations being eventually linked as to form a common gene pool.
The classification of species has been profoundly affected by technological advances that have allowed researchers to determine relatedness based on molecular markers, starting with the comparatively crude blood plasma precipitation assays in the mid-20th century to Charles Sibley's ground-breaking DNA-DNA hybridisation studies in the 1970s leading to DNA sequencing techniques. The results of these techniques caused revolutionary changes in the higher taxonomic categories (such as phyla and classes), resulting in the reordering of many branches of the phylogenetic tree (see also: molecular phylogeny). For taxonomic categories below genera, the results have been mixed so far; the pace of evolutionary change on the molecular level is rather slow, yielding clear differences only after considerable periods of reproductive separation. DNA-DNA hybridization results have led to misleading conclusions, the Pomarine Skua - Great Skua phenomenon being a famous example. Turtles have been determined to evolve with just one-eighth of the speed of other reptiles on the molecular level, and the rate of molecular evolution in albatrosses is half of what is found in the rather closely related storm-petrels. The hybridization technique is now obsolete and is replaced by more reliable computational approaches for sequence comparison. Molecular taxonomy is not directly based on the evolutionary processes, but rather on the overall change brought upon by these processes. The processes that lead to the generation and maintenance of variation such as mutation, crossover and selection are not uniform (see also molecular clock). DNA is only extremely rarely a direct target of natural selection rather than changes in the DNA sequence enduring over generations being a result of the latter; for example, silent transition-transversion combinations would alter the melting point of the DNA sequence, but not the sequence of the encoded proteins and thus are a possible example where, for example in microorganisms, a mutation confers a change in fitness all by itself. | Species
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
In biology, a species is one of the basic units of biological classification and a taxonomic rank. A species is often defined as a group of organisms capable of interbreeding and producing fertile offspring. While in many cases this definition is adequate, more precise or differing measures are often used, such as based on similarity of DNA or morphology. Presence of specific locally-adapted traits may further subdivide species into subspecies.
The commonly used names for plant and animal taxa sometimes correspond to species: for example, "lion," "walrus," and "Camphor tree," each refers to a species. In other cases common names do not: for example, "deer" refers to a family of 34 species, including Eld's Deer, Red Deer and Wapiti (Elk). The last two species were once considered a single species, illustrating how species boundaries may change with increased scientific knowledge.
Each species is placed within a single genus. This is a hypothesis that the species is more closely related to other species within its genus than to species of other genera. All species are given a binomial name consisting of the generic name and specific name (or specific epithet). For example, Pinus palustris (commonly known as the Longleaf Pine).
A usable definition of the word "species" and reliable methods of identifying particular species are essential for stating and testing biological theories and for measuring biodiversity. Traditionally, multiple examples of a proposed species must be studied for unifying characters before it can be regarded as a species. Extinct species known only from fossils are generally difficult to give precise taxonomic rankings to. A species which has been described scientifically can be referred to by its binomial names.
Nevertheless, as Charles Darwin remarked,
Because of the difficulties with both defining and tallying the total numbers of different species in the world, it is estimated that there are anywhere between 2 and 100 million different species.[2]
# Binomial convention for naming species
In scientific classification, a species is assigned a two-part name, treated as Latin, although roots from any language can be used as well as names of locales or individuals. The genus is listed first (with its leading letter capitalized), followed by a second term: for example, gray wolves belong to the species Canis lupus, coyotes to Canis latrans, golden jackals to Canis aureus, etc., and all of those belong to the genus Canis (which also contains many other species). The name of the species is the whole binomial, not just the second term (which may be called specific name for animals).
The binomial naming convention, later formalized in the biological codes of nomenclature, was first used by Leonhart Fuchs and introduced as the standard by Carolus Linnaeus in his 1758 classical work Systema Naturae 10th edition. As a result, it is sometimes called the "binomial nomenclature." At that time, the chief biological theory was that species represented independent acts of creation by God and were therefore considered objectively real and immutable.
## Abbreviation
Books and articles sometimes intentionally do not identify species fully and use the abbreviation "sp." in the singular or "spp." in the plural in place of the specific epithet: for example, Canis sp. This commonly occurs in the following types of situation:
- The authors are confident that some individuals belong to a particular genus but are not sure to which exact species they belong. This is particularly common in paleontology.
- The authors use "spp." as a short way of saying that something applies to many species within a genus, but do not wish to say that it applies to all species within that genus. If scientists mean that something applies to all species with a genus, they use the genus name without the specific epithet.
In books and articles that use the Latin alphabet, genus and species names are usually printed in italics. If using "sp." and "spp.," these should not be italicized.
# Difficulty of defining "species" and identifying particular species
It is surprisingly difficult to define the word "species" in a way that applies to all naturally occurring organisms, and the debate among biologists about how to define "species" and how to identify actual species is called the species problem.
Most textbooks define a species as all the individual organisms of a natural population that generally interbreed at maturity in the wild and whose interbreeding produces fertile offspring. Various parts of this definition are there to exclude some unusual or artificial matings:
- Those which occur only in captivity (when the animal's normal mating partners may not be available) or as a result of deliberate human action.
- Animals which may be physically and physiologically capable of mating but do not normally do so in the wild, for whatever reason.
- Animals whose offspring are normally sterile. For example, mules and hinnies have never (so far) produced further offspring when mated with a creature of the same type (a mule with a mule, or a hinny with a hinny).
## Living organisms
The typical textbook definition (above) works well for most multi-celled organisms, but there are several types of situations in which it breaks down:
- By definition it applies only to organisms which reproduce sexually. So it does not work for asexually reproducing single-celled organisms and for the relatively few parthenogenetic multi-celled organisms. The term "phylotype" is often applied to such organisms.
- Some hybrids, e.g., mules, hinnies, ligers and tigons, apparently cannot produce offspring when mated with one of their own kind (e.g. a mule with a mule), but sometimes do produce offspring when mated with members of one of the parent species (e.g. a liger with a lion). Usually in such hybrids the males are sterile, so one could improve the basic textbook definition by changing "... whose interbreeding produces fertile offspring" to "... whose interbreeding produces offspring in which both sexes are normally fertile".
- In ring species, members of adjacent populations interbreed successfully but members of widely-separated populations do not.
- In a few cases it may be physically impossible for animals which are members of the same species to mate, for example a Great Dane and a Chihuahua are both dogs and therefore members of the same species, but cannot mate because of the great difference in size and weight (physical build).
Horizontal gene transfer makes it even more difficult to define the word "species". There is strong evidence of horizontal gene transfer between very dissimilar groups of procaryotes, and possibly between dissimilar groups of single-celled eucaryotes; and Williamson[3] argues that there is evidence for it in some crustaceans and echinoderms. All definitions of the word "species" assume that an organism gets all its genes from one or two parents which are very like that organism, but horizontal gene transfer makes that assumption false.
## Extinct organisms
Many extinct organisms are known only from fossils, which generally only preserve hard features. Fossils have not (so far) shown us what bred with what, and cannot tell us whether any resulting offspring would have been fertile. So paleontologists generally use either the morphological or the evolutionary definition of species (see below).
Paleontologists also have to cope with another difficulty: one species may gradually evolve into one or more others after a few million years; the original type of organism and the final one are so different that one could not regard the ancestors and the descendants as members of the same species if they existed at the same time; but the intermediate types are so similar to the next and previous types that one cannot say exactly where species A changed into species B. Paleontologists devised the concept of chronospecies to describe the simplest case, where at the end of the process there is only one descendant type of organism and there are no longer any individuals of the ancestral type. But even this refinement does not work in cases where several descendant types are alive at the same time or where the ancestral type and at least one descendant type are alive at the same time - and both of these situations are common in the evolution of life on Earth. Human evolution may offer a striking example: some geneticists have suggested that for about 1 million years there was some interbreeding between the early ancestors of humans and the early ancestors of chimpanzees (James Mallet and other MIT and Harvard scientists, as quoted in the news magazine This Week, June 9, 2006).
# Definitions of species
The question of how best to define "species" is one that has occupied biologists for centuries, and the debate itself has become known as the species problem. One definition that is widely used is that a species is a group of actually or potentially interbreeding populations that are reproductively isolated from other such groups.[4]
The definition of a species given above is derived from the behavioral biologist Ernst Mayr, and is somewhat unrealistic. Since it assumes sexual reproduction, it leaves the term undefined for a large class of organisms that reproduce asexually. Biologists frequently do not know whether two morphologically similar groups of organisms are "potentially" capable of interbreeding. Further, there is considerable variation in the degree to which hybridization may succeed under natural and experimental conditions, or even in the degree to which some organisms use sexual reproduction between individuals to breed. Consequently, several lines of thought in the definition of species exist:
In practice, these definitions often coincide, and the differences between them are more a matter of emphasis than of outright contradiction. Nevertheless, no species concept yet proposed is entirely objective, or can be applied in all cases without resorting to judgment. Given the complexity of life, some have argued that such an objective definition is in all likelihood impossible, and biologists should settle for the most practical definition. For most vertebrates, this is the biological species concept (BSC), and to a lesser extent (or for different purposes) the phylogenetic species concept (PSC). Many BSC subspecies are considered species under the PSC; the difference between the BSC and the PSC can be summed up insofar as that the BSC defines a species as a consequence of manifest evolutionary history, while the PSC defines a species as a consequence of manifest evolutionary potential. Thus, a PSC species is "made" as soon as an evolutionary lineage has started to separate, while a BSC species starts to exist only when the lineage separation is complete. Accordingly, there can be considerable conflict between alternative classifications based upon the PSC versus BSC, as they differ completely in their treatment of taxa that would be considered subspecies under the latter model (e.g., the numerous subspecies of honey bees).
# Importance in biological classification
The idea of species has a long history. It is one of the most important levels of classification, for several reasons:
- It often corresponds to what lay people treat as the different basic kinds of organism - dogs are one species, cats another.
- It is the standard binomial nomenclature (or trinomial nomenclature) by which scientists typically refer to organisms.
- It is the highest taxonomic level which mostly cannot be made more or less inclusionary.
After thousands of years of use, the concept remains central to biology and a host of related fields, and yet also remains at times ill-defined.
# Implications of assignment of species status
The naming of a particular species should be regarded as a hypothesis about the evolutionary relationships and distinguishability of that group of organisms. As further information comes to hand, the hypothesis may be confirmed or refuted. Sometimes, especially in the past when communication was more difficult, taxonomists working in isolation have given two distinct names to individual organisms later identified as the same species. When two named species are discovered to be of the same species, the older species name is usually retained, and the newer species name dropped, a process called synonymization, or convivially, as lumping. Dividing a taxon into multiple, often new, taxons is called splitting. Taxonomists are often referred to as "lumpers" or "splitters" by their colleagues, depending on their personal approach to recognizing differences or commonalities between organisms (see lumpers and splitters).
Traditionally, researchers relied on observations of anatomical differences, and on observations of whether different populations were able to interbreed successfully, to distinguish species; both anatomy and breeding behavior are still important to assigning species status. As a result of the revolutionary (and still ongoing) advance in microbiological research techniques, including DNA analysis, in the last few decades, a great deal of additional knowledge about the differences and similarities between species has become available. Many populations which were formerly regarded as separate species are now considered to be a single taxon, and many formerly grouped populations have been split. Any taxonomic level (species, genus, family, etc.) can be synonymized or split, and at higher taxonomic levels, these revisions have been still more profound.
From a taxonomical point of view, groups within a species can be defined as being of a taxon hierarchically lower than a species. In zoology only the subspecies is used, while in botany the variety, subvariety, and form are used as well. In conservation biology, the concept of evolutionary significant units (ESU) is used, which may be define either species or smaller distinct population segments.
# The isolation species concept in more detail
In general, for large, complex, organisms that reproduce sexually (such as mammals and birds), one of several variations on the isolation or biological species concept is employed. Often, the distinction between different species, even quite closely related ones, is simple. Horses (Equus caballus) and donkeys (Equus asinus) are easily told apart even without study or training, and yet are so closely related that they can interbreed after a fashion. Because the result, a mule or hinny, is not fertile, they are clearly separate species.
But many cases are more difficult to decide. This is where the isolation species concept diverges from the evolutionary species concept. Both agree that a species is a lineage that maintains its integrity over time, that is diagnosably different from other lineages (else we could not recognise it), is reproductively isolated (else the lineage would merge into others, given the chance to do so), and has a working intra-species recognition system (without which it could not continue). In practice, both also agree that a species must have its own independent evolutionary history—otherwise the characteristics just mentioned would not apply. The species concepts differ in that the evolutionary species concept does not make predictions about the future of the population: it simply records that which is already known. In contrast, the isolation species concept refuses to assign the rank of species to populations that, in the best judgement of the researcher, would recombine with other populations if given the chance to do so.
## The isolation question
There are, essentially, two questions to resolve. First, is the proposed species consistently and reliably distinguishable from other species? Second, is it likely to remain so in the future? To take the second question first, there are several broad geographic possibilities.
- The proposed species are sympatric—they occupy the same habitat. Observation of many species over the years has failed to establish even a single instance of two diagnostically different populations that exist in sympatry and have then merged to form one united population. Without reproductive isolation, population differences cannot develop, and given reproductive isolation, gene flow between the populations cannot merge the differences. This is not to say that cross breeding does not take place at all, simply that it has become negligible. Generally, the hybrid individuals are less capable of successful breeding than pure-bred individuals of either species.
- The proposed species are allopatric—they occupy different geographical areas. Obviously, it is not possible to observe reproductive isolation in allopatric groups directly. Often it is not possible to achieve certainty by experimental means either: even if the two proposed species interbreed in captivity, this does not demonstrate that they would freely interbreed in the wild, nor does it always provide much information about the evolutionary fitness of hybrid individuals. A certain amount can be inferred from other experimental methods: for example, do the members of population A respond appropriately to playback of the recorded mating calls of population B? Sometimes, experiments can provide firm answers. For example, there are seven pairs of apparently almost identical marine snapping shrimp (Alpheus) populations on either side of the Isthmus of Panama, which did not exist until about 3 million years ago. Until then, it is assumed, they were members of the same seven species. But when males and females from opposite sides of the isthmus are placed together, they fight instead of mating. Even if the isthmus were to sink under the waves again, the populations would remain genetically isolated: therefore they are now different species. In many cases, however, neither observation nor experiment can produce certain answers, and the determination of species rank must be made on a 'best guess' basis from a general knowledge of other related organisms.
- The proposed species are parapatric—they have breeding ranges that abut but do not overlap. This is fairly rare, particularly in temperate regions. The dividing line is often a sudden change in habitat (an ecotone) like the edge of a forest or the snow line on a mountain, but can sometimes be remarkably trivial. The parapatry itself indicates that the two populations occupy such similar ecological roles that they cannot coexist in the same area. Because they do not crossbreed, it is safe to assume that there is a mechanism, often behavioral, that is preventing gene flow between the populations, and that therefore they should be classified as separate species.
- There is a hybrid zone where the two populations mix. Typically, the hybrid zone will include representatives of one or both of the 'pure' populations, plus first-generation and back-crossing hybrids. The strength of the barrier to genetic transmission between the two pure groups can be assessed by the width of the hybrid zone relative to the typical dispersal distance of the organisms in question. The dispersal distance of oaks, for example, is the distance that a bird or squirrel can be expected to carry an acorn; the dispersal distance of Numbats is about 15 kilometres, as this is as far as young Numbats will normally travel in search of vacant territory to occupy after leaving the nest. The narrower the hybrid zone relative to the dispersal distance, the less gene flow there is between the population groups, and the more likely it is that they will continue on separate evolutionary paths. Nevertheless, it can be very difficult to predict the future course of a hybrid zone; the decision to define the two hybridizing populations as either the same species or as separate species is difficult and potentially controversial.
- The variation in the population is clinal; at either extreme of the population's geographic distribution, typical individuals are clearly different, but the transition between them is seamless and gradual. For example, the Koalas of northern Australia are clearly smaller and lighter in colour than those of the south, but there is no particular dividing line: the further south an individual Koala is found, the larger and darker it is likely to be; Koalas in intermediate regions are intermediate in weight and colour. In contrast, over the same geographic range, black-backed (northern) and white-backed (southern) Australian Magpies do not blend from one type to another: northern populations have black backs, southern populations white backs, and there is an extensive hybrid zone where both 'pure' types are common, as are crossbreeds. The variation in Koalas is clinal (a smooth transition from north to south, with populations in any given small area having a uniform appearance), but the variation in magpies is not clinal. In both cases, there is some uncertainty regarding correct classification, but the consensus view is that species rank is not justified in either. The gene flow between northern and southern magpie populations is judged to be sufficiently restricted to justify terming them subspecies (not full species); but the seamless way that local Koala populations blend one into another shows that there is substantial gene flow between north and south. As a result, experts tend to reject even subspecies rank in this case.
## The difference question
Obviously, when defining a species, the geographic circumstances become meaningful only if the populations groups in question are clearly different: if they are not consistently and reliably distinguishable from one another, then we have no grounds for believing that they might be different species. The key question in this context, is "how different is different?" and the answer is usually "it all depends".
In theory, it would be possible to recognise even the tiniest of differences as sufficient to delineate a separate species, provided only that the difference is clear and consistent (and that other criteria are met). There is no universal rule to state the smallest allowable difference between two species, but in general, very trivial differences are ignored on the twin grounds of simple practicality, and genetic similarity: if two population groups are so close that the distinction between them rests on an obscure and microscopic difference in morphology, or a single base substitution in a DNA sequence, then a demonstration of restricted gene flow between the populations will probably be difficult in any case.
More typically, one or other of the following requirements must be met:
- It is possible to reliably measure a quantitative difference between the two groups that does not overlap. A population has, for example, thicker fur, rougher bark, longer ears, or larger seeds than another population, and although this characteristic may vary within each population, the two do not grade into one another, and given a reasonably large sample size, there is a definite discontinuity between them. Note that this applies to populations, not individual organisms, and that a small number of exceptional individuals within a population may 'break the rule' without invalidating it. The less a quantitative difference varies within a population and the more it varies between populations, the better the case for making a distinction. Nevertheless, borderline situations can only be resolved by making a 'best-guess' judgement.
- It is possible to distinguish a qualitative difference between the populations; a feature that does not vary continuously but is either entirely present or entirely absent. This might be a distinctively shaped seed pod, an extra primary feather, a particular courting behaviour, or a clearly different DNA sequence.
Sometimes it is not possible to isolate a single difference between species, and several factors must be taken in combination. This is often the case with plants in particular. In eucalypts, for example, Corymbia ficifolia cannot be reliably distinguished from its close relative Corymbia calophylla by any single measure (and sometimes individual trees cannot be definitely assigned to either species), but populations of Corymbia can be clearly told apart by comparing the colour of flowers, bark, and buds, number of flowers for a given size of tree, and the shape of the leaves and fruit.
When using a combination of characteristics to distinguish between populations, it is necessary to use a reasonably small number of factors (if more than a handful are needed, the genetic difference between the populations is likely to be insignificant and is unlikely to endure into the future), and to choose factors that are functionally independent (height and weight, for example, should usually be considered as one factor, not two).
# Historical development of the species concept
In the earliest works of science, a species was simply an individual organism that represented a group of similar or nearly identical organisms. No other relationships beyond that group were implied. Aristotle used the words genus and species to mean generic and specific categories. Aristotle and other pre-Darwinian scientists took the species to be distinct and unchanging, with an "essence", like the chemical elements. When early observers began to develop systems of organization for living things, they began to place formerly isolated species into a context. Many of these early delineation schemes would now be considered whimsical and these included consanguinity based on color (all plants with yellow flowers) or behavior (snakes, scorpions and certain biting ants).
In the 18th century Carolus Linnaeus classified organisms according to differences in the form of reproductive apparatus. Although his system of classification sorts organisms according to degrees of similarity, it made no claims about the relationship between similar species. At that time, it was still widely believed that there was no organic connection between species, no matter how similar they appeared. This approach also suggested a type of idealism: the notion that each species existed as an "ideal form". Although there are always differences (although sometimes minute) between individual organisms, Linnaeus considered such variation problematic. He strove to identify individual organisms that were exemplary of the species, and considered other non-exemplary organisms to be deviant and imperfect.
By the 19th century most naturalists understood that species could change form over time, and that the history of the planet provided enough time for major changes. Jean-Baptiste Lamarck, in his 1809 Zoological Philosophy, offered one of the first logical arguments against creationism. The new emphasis was on determining how a species could change over time. Lamarck suggested that an organism could pass on an acquired trait to its offspring, i.e., the giraffe's long neck was attributed to generations of giraffes stretching to reach the leaves of higher treetops (this well-known and simplistic example, however, does not do justice to the breadth and subtlety of Lamarck's ideas). With the acceptance of the natural selection idea of Charles Darwin in the 1860s, however, Lamarck's view of goal-oriented evolution, also known as a teleological process, was eclipsed. Recent interest in inheritance of acquired characteristics centers around epigenetic processes, e.g. methylation, that do not affect DNA sequences, but instead alter expression in an inheritable manner. Thus, neo-lamarckism, as it is sometimes termed, is not a challenge to the theory of evolution by natural selection.
Charles Darwin and Alfred Wallace provided what scientists now consider as the most powerful and compelling theory of evolution. Darwin argued that it was populations that evolved, not individuals. His argument relied on a radical shift in perspective from that of Linnaeus: rather than defining species in ideal terms (and searching for an ideal representative and rejecting deviations), Darwin considered variation among individuals to be natural. He further argued that variation, far from being problematic, actually provides the explanation for the existence of distinct species.
Darwin's work drew on Thomas Malthus' insight that the rate of growth of a biological population will always outpace the rate of growth of the resources in the environment, such as the food supply. As a result, Darwin argued, not all the members of a population will be able to survive and reproduce. Those that did will, on average, be the ones possessing variations—however slight—that make them slightly better adapted to the environment. If these variable traits are heritable, then the offspring of the survivors will also possess them. Thus, over many generations, adaptive variations will accumulate in the population, while counter-adaptive will be eliminated.
It should be emphasized that whether a variation is adaptive or non-adaptive depends on the environment: different environments favor different traits. Since the environment effectively selects which organisms live to reproduce, it is the environment (the "fight for existence") that selects the traits to be passed on. This is the theory of evolution by natural selection. In this model, the length of a giraffe's neck would be explained by positing that proto-giraffes with longer necks would have had a significant reproductive advantage to those with shorter necks. Over many generations, the entire population would be a species of long-necked animals.
In 1859, when Darwin published his theory of natural selection, the mechanism behind the inheritance of individual traits was unknown. Although Darwin made some speculations on how traits are inherited (pangenesis), his theory relies only on the fact that inheritable traits exist, and are variable (which makes his accomplishment even more remarkable.) Although Gregor Mendel's paper on genetics was published in 1866, its significance was not recognized. It was not until 1900 that his work was rediscovered by Hugo de Vries, Carl Correns and Erich von Tschermak, who realised that the "inheritable traits" in Darwin's theory are genes.
The theory of the evolution of species through natural selection has two important implications for discussions of species -- consequences that fundamentally challenge the assumptions behind Linnaeus' taxonomy. First, it suggests that species are not just similar, they may actually be related. Some students of Darwin argue that all species are descended from a common ancestor. Second, it supposes that "species" are not homogeneous, fixed, permanent things; members of a species are all different, and over time species change. This suggests that species do not have any clear boundaries but are rather momentary statistical effects of constantly changing gene-frequencies. One may still use Linnaeus' taxonomy to identify individual plants and animals, but one can no longer think of species as independent and immutable.
The rise of a new species from a parental line is called speciation. There is no clear line demarcating the ancestral species from the descendant species.
Although the current scientific understanding of species suggests that there is no rigorous and comprehensive way to distinguish between different species in all cases, biologists continue to seek concrete ways to operationalize the idea. One of the most popular biological definitions of species is in terms of reproductive isolation; if two creatures cannot reproduce to produce fertile offspring, then they are in different species. This definition captures a number of intuitive species boundaries, but it remains imperfect. It has nothing to say about species that reproduce asexually, for example, and it is very difficult to apply to extinct species. Moreover, boundaries between species are often fuzzy: there are examples where members of one population can produce fertile offspring with a second population, and members of the second population can produce fertile offspring with members of a third population, but members of the first and third population cannot produces fertile offspring. Consequently, some people reject this definition of a species.
Richard Dawkins defines two organisms as conspecific if and only if they have the same number of chromosomes and, for each chromosome, both organisms have the same number of nucleotides (The Blind Watchmaker, p. 118). However, most if not all taxonomists would strongly disagree. For example, in many amphibians, most notably in New Zealand's Leiopelma frogs, the genome consists of "core" chromosomes which are mostly invariable and accessory chromosomes, of which exist a number of possible combinations. Even though the chromosome numbers are highly variable between populations, these can interbreed successfully and form a single evolutionary unit. In plants, polyploidy is extremely commonplace with few restrictions on interbreeding; as individuals with an odd number of chromosome sets are usually sterile, depending on the actual number of chromosome sets present, this results in the odd situation where some individuals of the same evolutionary unit can interbreed with certain others and some cannot, with all populations being eventually linked as to form a common gene pool.
The classification of species has been profoundly affected by technological advances that have allowed researchers to determine relatedness based on molecular markers, starting with the comparatively crude blood plasma precipitation assays in the mid-20th century to Charles Sibley's ground-breaking DNA-DNA hybridisation studies in the 1970s leading to DNA sequencing techniques. The results of these techniques caused revolutionary changes in the higher taxonomic categories (such as phyla and classes), resulting in the reordering of many branches of the phylogenetic tree (see also: molecular phylogeny). For taxonomic categories below genera, the results have been mixed so far; the pace of evolutionary change on the molecular level is rather slow, yielding clear differences only after considerable periods of reproductive separation. DNA-DNA hybridization results have led to misleading conclusions, the Pomarine Skua - Great Skua phenomenon being a famous example. Turtles have been determined to evolve with just one-eighth of the speed of other reptiles on the molecular level, and the rate of molecular evolution in albatrosses is half of what is found in the rather closely related storm-petrels. The hybridization technique is now obsolete and is replaced by more reliable computational approaches for sequence comparison. Molecular taxonomy is not directly based on the evolutionary processes, but rather on the overall change brought upon by these processes. The processes that lead to the generation and maintenance of variation such as mutation, crossover and selection are not uniform (see also molecular clock). DNA is only extremely rarely a direct target of natural selection rather than changes in the DNA sequence enduring over generations being a result of the latter; for example, silent transition-transversion combinations would alter the melting point of the DNA sequence, but not the sequence of the encoded proteins and thus are a possible example where, for example in microorganisms, a mutation confers a change in fitness all by itself. | https://www.wikidoc.org/index.php/Binomial_names | |
056f951c2b2831cc319971a73570069bbba39489 | wikidoc | Biochip | Biochip
The development of biochips is a major thrust of the rapidly growing biotechnology industry, which encompasses a very diverse range of
research efforts including genomics, proteomics, computational biology, and
pharmaceuticals, among other activities. Advances in
these areas are giving scientists new methods for unraveling the complex
biochemical processes occurring inside cells, with the larger goal of
understanding and treating human diseases. At the same time, the
semiconductor industry has been steadily perfecting the science of
microminiaturization. The merging of these two fields in recent years has
enabled biotechnologists to begin packing their traditionally bulky
sensing tools into smaller and smaller spaces, onto so-called biochips. These
chips are essentially miniaturized laboratories that can perform hundreds or
thousands of simultaneous biochemical reactions. Biochips enable researchers
to quickly screen large numbers of biological analytes for a variety of
purposes, from disease diagnosis to detection of bioterrorism agents.
# History
The development of biochips was a long history, starting with early work on
the underlying sensor technology. One of the first portable, chemistry-based
sensors was the glass pH electrode, invented in 1922 by
Hughes (Hughes, 1922). Measurement of pH was accomplished by
detecting the potential difference developed across a thin glass membrane
selective to the permeation of hydrogen ions; this selectivity was achieved
by exchanges between H+ and SiO sites in the glass. The basic concept of
using exchange sites to create permselective membranes was used to develop
-ther ion sensors in subsequent years. For example, a K+ sensor was
produced by incorporating valinomycin into a thin membrane (Schultz, 1996).
Over thirty years elapsed before the first true biosensor (i.e. a
sensor utilizing biological molecules) emerged. In 1956, Leland Clark
published a paper on an oxygen sensing electrode (Clark, 1956_41).
This device became the basis for a glucose sensor developed in 1962 by Clark
and colleague Lyons which utilized glucose oxidase molecules embedded in a
dialysis membrane (Clark, 1962). The enzyme functioned in the
presence of glucose to decrease the amount of oxygen available to the oxygen
electrode, thereby relating oxygen levels to glucose concentration. This and
similar biosensors became known as enzyme electrodes, and are still in use
today.
In 1953, Watson and Crick announced their discovery of the now familiar
double helix structure of DNA molecules and set the stage for genetics
research that continues to the present day (Nelson, 2000). The development
-f sequencing techniques in 1977 by Gilbert (Maxam, 1977) and
Sanger (Sanger, 1977) (working separately) enabled researchers to
directly read the genetic codes that provide instructions for
protein synthesis. This research showed how hybridization of complementary single
-ligonucleotide strands could be used as a basis for DNA sensing. Two
additional developments enabled the technology used in modern DNA-based
biosensors. First, in 1983 Kary Mullis invented the
polymerase chain reaction
(PCR) technique (Nelson, 2000), a method for amplifying DNA concentrations.
This discovery made possible the detection of extremely small quantities of
DNA in samples. Second, in 1986 Hood and coworkers devised a method to label
DNA molecules with fluorescent tags instead of
radiolabels (Smith, 1986), thus enabling hybridization experiments to
be observed optically.
The rapid technological advances of the biochemistry and semiconductor fields
in the 1980s led to the large scale development of biochips in the 1990s.
At this time, it became clear that biochips were largely a "platform"
technology which consisted of several separate, yet integrated components.
Figure 1 shows the makeup of a typical biochip platform.
The actual sensing component (or "chip") is just one piece of a complete
analysis system. Transduction must be done to translate the actual sensing
event (DNA binding, oxidation/reduction, etc.) into a format
understandable by a computer (voltage, light intensity, mass, etc.),
which then enables additional analysis and processing to produce a final,
human-readable output. The multiple technologies needed to make a successful
biochip -- from sensing chemistry, to microarraying, to signal processing --
require a true multidisciplinary approach, making the barrier to entry steep.
One of the first commercial biochips was introduced by Affymetrix. Their
"GeneChip" products contain thousands of individual DNA sensors for use in
sensing defects, or single nucleotide polymorphisms (SNPs), in genes such as
p53 (a tumor suppressor) and BRCA1 and BRCA2 (related to breast
cancer) (Cheng, 2001). The chips are produced using microlithography
techniques traditionally used to fabricate integrated circuits (see below).
Today, a large variety of biochip technologies are either in development or
being commercialized. Numerous advancements continue to be made in sensing
research that enable new platforms to be developed for new applications.
Cancer diagnosis through DNA typing is just one market opportunity. A variety
-f industries currently desire the ability to simultaneously screen for a
wide range of chemical and biological agents, with purposes ranging from
testing public water systems for disease agents to screening airline cargo
for explosives. Pharmaceutical companies wish to combinatorially screen drug
candidates against target enzymes. To achieve these ends, DNA, RNA, proteins,
and even living cells are being employed as sensing mediators on biochips.
Numerous transduction methods can be employed including surface plasmon resonance, fluorescence, and chemiluminescence. The particular sensing and
transduction techniques chosen depend on factors such as price, sensitivity,
and reusability.
# Microarray fabrication
The microarray -- the dense, two-dimensional grid of biosensors -- is the critical component of a biochip platform. Typically, the sensors are deposited on a flat substrate, which may either be passive (e.g. silicon or glass) or active, the latter
consisting of integrated electronics or micromechanical devices that perform or assist signal transduction. Surface chemistry is used to covalently bind the sensor molecules to the substrate medium. The fabrication of microarrays is non-trivial and is a major economic and technological hurdle that may
ultimately decide the success of future biochip platforms. The primary manufacturing challenge is the process of placing each sensor at a specific position (typically on a Cartesian grid) on the substrate. Various means exist to achieve the placement, but typically robotic micro-pipetting (Schena, 1995) or micro-printing (MacBeath, 1999) systems are used to place tiny spots of sensor material on the chip surface. Because each sensor is unique, only a few spots can be placed at a time. The low-throughput nature of this
process results in high manufacturing costs.
Fodor and colleagues developed a unique fabrication process (later used by
Affymetrix) in which a series of microlithography steps is used to
combinatorially synthesize hundreds of thousands of unique, single-stranded
DNA sensors on a substrate one nucleotide at a
time (Fodor, 1991; Pease, 1994). One lithography step is needed per base type; thus, a total
-f four steps is required per nucleotide level. Although this technique is
very powerful in that many sensors can be created simultaneously, it is
currently only feasible for creating short DNA strands (15-25 nucleotides).
Reliability and cost factors limit the number of photolithography steps that
can be done. Furthermore, light-directed combinatorial synthesis techniques
are not currently possible for proteins or other sensing molecules.
As noted above, most microarrays consist of a Cartesian grid of sensors. This
approach is used chiefly to map or "encode" the coordinate of each sensor
to its function. Sensors in these arrays typically use a universal signaling
technique (e.g. fluorescence), thus making coordinates their only
identifying feature. These arrays must be made using a serial process
(i.e. requiring multiple, sequential steps) to ensure that each sensor
is placed at the correct position.
"Random" fabrication, in which the sensors are placed at arbitrary
positions on the chip, is an alternative to the serial method. The tedious and expensive positioning process is
not required, enabling the use of parallelized self-assembly techniques. In
this approach, large batches of identical sensors can be produced; sensors
from each batch are then combined and assembled into an array. A
non-coordinate based encoding scheme must be used to identify each sensor. As
the figure shows, such a design was first demonstrated (and later
commercialized by Illumina) using functionalized beads placed randomly in the
wells of an etched fiber optic
cable (Steemers, 2000; Michael, 1998) Each bead was uniquely
encoded with a fluorescent signature. However, this encoding scheme is
limited in the number of unique dye combinations that be can be used and
successfully differentiated.
# Protein Biochip Array and Other Microarray Technologies
Microarrays are not limited to DNA analysis; protein microarrays, antibody microarray, Chemical Compound Microarray can also be produced using biochips. Randox Laboratories Ltd. launched Evidence®, the first protein Biochip Array Technology analyzer in 2003. In protein Biochip Array Technology, the biochip replaces the ELISA plate or cuvette as the reaction platform. The biochip is used to simultaneously analyze a panel of related tests in a single sample, producing a patient profile. The patient profile can be used in disease screening, diagnosis, monitoring disease progression or monitoring treatment. Performing multiple analyses simultaneously, described as multiplexing, allows a significant reduction in processing time and the amount of patient sample required. Biochip Array Technology is a novel application of a familiar methodology, using sandwich, competitive and antibody-capture immunoassays. The difference from conventional immunoassays is that the capture ligands are covalently attached to the surface of the biochip in an ordered array rather than in solution.
In sandwich assays an enzyme-labelled antibody is used; in competitive assays an enzyme-labelled antigen is used. On antibody-antigen binding a chemiluminescence reaction produces light. Detection is by a charge-coupled device (CCD) camera. The CCD camera is a sensitive and high-resolution sensor able to accurately detect and quantify very low levels of light. The test regions are located using a grid pattern then the chemiluminescence signals are analysed by imaging software to rapidly and simultaneously quantify the individual analytes.
Details about other array technologies can be found in the following pages: Antibody microarray and Chemical Compound Microarray.
# Bioethics
When the question of ethics come up there is never a clear cut answer, nor should there be. Since no one has actually implemented many types of future biotechnology, interpreting moral issue at this point is very difficult. However, this debate is relevant today and it is critical to begin debate now. Arthur Caplan of University of Pennsylvania School of Medicine explains that “Crossing into this area will be so startling, so momentous, and so socially unnerving that the prospect of doing so demands proactive ethical, theological, and scientific discussion.”
Bioethics is the collaborative investigation of biology, scientific technology, and ethical issues. Van Potter’s definition in 1971 states that bioethics is “biology combined with diverse humanistic knowledge forging a science that sets a system on medical and environmental priorities for acceptable survival.”
Genetic research has many life altering benefits. Genetic research can be used to prevent genetic defects, eliminate disease and replace vital organs. This will save many lives. However, we must realize the potential impact on life itself. Scientists are advised to come up with plans and submit these plans to associated groups with both scientific and ethical expertise for review, before entering into development of new biotechnology. Reviews should be conducted nationally and or internationally. As well, the development should be contained in strict biological confinement until the implications are understood.
Ethics is concerned with what is morally good and bad or right and wrong. Obviously, with regards to bioethics there is a thin line between what is ethical and what is not. Scientists have an ethical obligation as do individuals to do what is right. There is no question whether or not biotechnology is a powerful new tool for modifying living organisms to benefit humankind. However, because biotechnology is so new to us we have yet to understand the risks involved with altering organisms. Until all the safety issues are resolves and ethical standards are put into stone government oversight is crucial. | Biochip
The development of biochips is a major thrust of the rapidly growing biotechnology industry, which encompasses a very diverse range of
research efforts including genomics, proteomics, computational biology, and
pharmaceuticals, among other activities. Advances in
these areas are giving scientists new methods for unraveling the complex
biochemical processes occurring inside cells, with the larger goal of
understanding and treating human diseases. At the same time, the
semiconductor industry has been steadily perfecting the science of
microminiaturization. The merging of these two fields in recent years has
enabled biotechnologists to begin packing their traditionally bulky
sensing tools into smaller and smaller spaces, onto so-called biochips. These
chips are essentially miniaturized laboratories that can perform hundreds or
thousands of simultaneous biochemical reactions. Biochips enable researchers
to quickly screen large numbers of biological analytes for a variety of
purposes, from disease diagnosis to detection of bioterrorism agents.
# History
The development of biochips was a long history, starting with early work on
the underlying sensor technology. One of the first portable, chemistry-based
sensors was the glass pH electrode, invented in 1922 by
Hughes (Hughes, 1922). Measurement of pH was accomplished by
detecting the potential difference developed across a thin glass membrane
selective to the permeation of hydrogen ions; this selectivity was achieved
by exchanges between H+ and SiO sites in the glass. The basic concept of
using exchange sites to create permselective membranes was used to develop
other ion sensors in subsequent years. For example, a K+ sensor was
produced by incorporating valinomycin into a thin membrane (Schultz, 1996).
Over thirty years elapsed before the first true biosensor (i.e. a
sensor utilizing biological molecules) emerged. In 1956, Leland Clark
published a paper on an oxygen sensing electrode (Clark, 1956_41).
This device became the basis for a glucose sensor developed in 1962 by Clark
and colleague Lyons which utilized glucose oxidase molecules embedded in a
dialysis membrane (Clark, 1962). The enzyme functioned in the
presence of glucose to decrease the amount of oxygen available to the oxygen
electrode, thereby relating oxygen levels to glucose concentration. This and
similar biosensors became known as enzyme electrodes, and are still in use
today.
In 1953, Watson and Crick announced their discovery of the now familiar
double helix structure of DNA molecules and set the stage for genetics
research that continues to the present day (Nelson, 2000). The development
of sequencing techniques in 1977 by Gilbert (Maxam, 1977) and
Sanger (Sanger, 1977) (working separately) enabled researchers to
directly read the genetic codes that provide instructions for
protein synthesis. This research showed how hybridization of complementary single
oligonucleotide strands could be used as a basis for DNA sensing. Two
additional developments enabled the technology used in modern DNA-based
biosensors. First, in 1983 Kary Mullis invented the
polymerase chain reaction
(PCR) technique (Nelson, 2000), a method for amplifying DNA concentrations.
This discovery made possible the detection of extremely small quantities of
DNA in samples. Second, in 1986 Hood and coworkers devised a method to label
DNA molecules with fluorescent tags instead of
radiolabels (Smith, 1986), thus enabling hybridization experiments to
be observed optically.
The rapid technological advances of the biochemistry and semiconductor fields
in the 1980s led to the large scale development of biochips in the 1990s.
At this time, it became clear that biochips were largely a "platform"
technology which consisted of several separate, yet integrated components.
Figure 1 shows the makeup of a typical biochip platform.
The actual sensing component (or "chip") is just one piece of a complete
analysis system. Transduction must be done to translate the actual sensing
event (DNA binding, oxidation/reduction, etc.) into a format
understandable by a computer (voltage, light intensity, mass, etc.),
which then enables additional analysis and processing to produce a final,
human-readable output. The multiple technologies needed to make a successful
biochip -- from sensing chemistry, to microarraying, to signal processing --
require a true multidisciplinary approach, making the barrier to entry steep.
One of the first commercial biochips was introduced by Affymetrix. Their
"GeneChip" products contain thousands of individual DNA sensors for use in
sensing defects, or single nucleotide polymorphisms (SNPs), in genes such as
p53 (a tumor suppressor) and BRCA1 and BRCA2 (related to breast
cancer) (Cheng, 2001). The chips are produced using microlithography
techniques traditionally used to fabricate integrated circuits (see below).
Today, a large variety of biochip technologies are either in development or
being commercialized. Numerous advancements continue to be made in sensing
research that enable new platforms to be developed for new applications.
Cancer diagnosis through DNA typing is just one market opportunity. A variety
of industries currently desire the ability to simultaneously screen for a
wide range of chemical and biological agents, with purposes ranging from
testing public water systems for disease agents to screening airline cargo
for explosives. Pharmaceutical companies wish to combinatorially screen drug
candidates against target enzymes. To achieve these ends, DNA, RNA, proteins,
and even living cells are being employed as sensing mediators on biochips.
Numerous transduction methods can be employed including surface plasmon resonance, fluorescence, and chemiluminescence. The particular sensing and
transduction techniques chosen depend on factors such as price, sensitivity,
and reusability.
# Microarray fabrication
The microarray -- the dense, two-dimensional grid of biosensors -- is the critical component of a biochip platform. Typically, the sensors are deposited on a flat substrate, which may either be passive (e.g. silicon or glass) or active, the latter
consisting of integrated electronics or micromechanical devices that perform or assist signal transduction. Surface chemistry is used to covalently bind the sensor molecules to the substrate medium. The fabrication of microarrays is non-trivial and is a major economic and technological hurdle that may
ultimately decide the success of future biochip platforms. The primary manufacturing challenge is the process of placing each sensor at a specific position (typically on a Cartesian grid) on the substrate. Various means exist to achieve the placement, but typically robotic micro-pipetting (Schena, 1995) or micro-printing (MacBeath, 1999) systems are used to place tiny spots of sensor material on the chip surface. Because each sensor is unique, only a few spots can be placed at a time. The low-throughput nature of this
process results in high manufacturing costs.
Fodor and colleagues developed a unique fabrication process (later used by
Affymetrix) in which a series of microlithography steps is used to
combinatorially synthesize hundreds of thousands of unique, single-stranded
DNA sensors on a substrate one nucleotide at a
time (Fodor, 1991; Pease, 1994). One lithography step is needed per base type; thus, a total
of four steps is required per nucleotide level. Although this technique is
very powerful in that many sensors can be created simultaneously, it is
currently only feasible for creating short DNA strands (15-25 nucleotides).
Reliability and cost factors limit the number of photolithography steps that
can be done. Furthermore, light-directed combinatorial synthesis techniques
are not currently possible for proteins or other sensing molecules.
As noted above, most microarrays consist of a Cartesian grid of sensors. This
approach is used chiefly to map or "encode" the coordinate of each sensor
to its function. Sensors in these arrays typically use a universal signaling
technique (e.g. fluorescence), thus making coordinates their only
identifying feature. These arrays must be made using a serial process
(i.e. requiring multiple, sequential steps) to ensure that each sensor
is placed at the correct position.
"Random" fabrication, in which the sensors are placed at arbitrary
positions on the chip, is an alternative to the serial method. The tedious and expensive positioning process is
not required, enabling the use of parallelized self-assembly techniques. In
this approach, large batches of identical sensors can be produced; sensors
from each batch are then combined and assembled into an array. A
non-coordinate based encoding scheme must be used to identify each sensor. As
the figure shows, such a design was first demonstrated (and later
commercialized by Illumina) using functionalized beads placed randomly in the
wells of an etched fiber optic
cable (Steemers, 2000; Michael, 1998) Each bead was uniquely
encoded with a fluorescent signature. However, this encoding scheme is
limited in the number of unique dye combinations that be can be used and
successfully differentiated.
# Protein Biochip Array and Other Microarray Technologies
Microarrays are not limited to DNA analysis; protein microarrays, antibody microarray, Chemical Compound Microarray can also be produced using biochips. Randox Laboratories Ltd. launched Evidence®, the first protein Biochip Array Technology analyzer in 2003. In protein Biochip Array Technology, the biochip replaces the ELISA plate or cuvette as the reaction platform. The biochip is used to simultaneously analyze a panel of related tests in a single sample, producing a patient profile. The patient profile can be used in disease screening, diagnosis, monitoring disease progression or monitoring treatment. Performing multiple analyses simultaneously, described as multiplexing, allows a significant reduction in processing time and the amount of patient sample required. Biochip Array Technology is a novel application of a familiar methodology, using sandwich, competitive and antibody-capture immunoassays. The difference from conventional immunoassays is that the capture ligands are covalently attached to the surface of the biochip in an ordered array rather than in solution.
In sandwich assays an enzyme-labelled antibody is used; in competitive assays an enzyme-labelled antigen is used. On antibody-antigen binding a chemiluminescence reaction produces light. Detection is by a charge-coupled device (CCD) camera. The CCD camera is a sensitive and high-resolution sensor able to accurately detect and quantify very low levels of light. The test regions are located using a grid pattern then the chemiluminescence signals are analysed by imaging software to rapidly and simultaneously quantify the individual analytes.
Details about other array technologies can be found in the following pages: Antibody microarray and Chemical Compound Microarray.
# Bioethics
When the question of ethics come up there is never a clear cut answer, nor should there be. Since no one has actually implemented many types of future biotechnology, interpreting moral issue at this point is very difficult. However, this debate is relevant today and it is critical to begin debate now. Arthur Caplan of University of Pennsylvania School of Medicine explains that “Crossing into this area will be so startling, so momentous, and so socially unnerving that the prospect of doing so demands proactive ethical, theological, and scientific discussion.”
Bioethics is the collaborative investigation of biology, scientific technology, and ethical issues. Van Potter’s definition in 1971 states that bioethics is “biology combined with diverse humanistic knowledge forging a science that sets a system on medical and environmental priorities for acceptable survival.”
Genetic research has many life altering benefits. Genetic research can be used to prevent genetic defects, eliminate disease and replace vital organs. This will save many lives. However, we must realize the potential impact on life itself. Scientists are advised to come up with plans and submit these plans to associated groups with both scientific and ethical expertise for review, before entering into development of new biotechnology. Reviews should be conducted nationally and or internationally. As well, the development should be contained in strict biological confinement until the implications are understood.
Ethics is concerned with what is morally good and bad or right and wrong. Obviously, with regards to bioethics there is a thin line between what is ethical and what is not. Scientists have an ethical obligation as do individuals to do what is right. There is no question whether or not biotechnology is a powerful new tool for modifying living organisms to benefit humankind. However, because biotechnology is so new to us we have yet to understand the risks involved with altering organisms. Until all the safety issues are resolves and ethical standards are put into stone government oversight is crucial. | https://www.wikidoc.org/index.php/Biochip | |
17f3937db93f0406b5760cc659e7055f3c0a7366 | wikidoc | Biofilm | Biofilm
# Overview
A biofilm is a complex aggregation of microorganisms marked by the excretion of a protective and adhesive matrix. Biofilms are also often characterized by surface attachment, structural heterogeneity, genetic diversity, complex community interactions, and an extracellular matrix of polymeric substances.
Single-celled organisms generally exhibit two distinct modes of behavior. The first is the familiar free floating, or planktonic, form in which single cells float or swim independently in some liquid medium. The second is an attached state in which cells are closely packed and firmly attached to each other and usually form a solid surface. A change in behavior is triggered by many factors, including quorum sensing, as well as other mechanisms that vary between species. When a cell switches modes, it undergoes a phenotypic shift in behavior in which large suites of genes are up- and down- regulated.
# Formation
Formation of a biofilm begins with the attachment of free-floating microorganisms to a surface. These first colonists adhere to the surface initially through weak, reversible van der Waals forces. If the colonists are not immediately separated from the surface, they can anchor themselves more permanently using cell adhesion molecules such as pili.
The first colonists facilitate the arrival of other cells by providing more diverse adhesion sites and beginning to build the matrix that holds the biofilm together. Some species are not able to attach to a surface on their own but are often able to anchor themselves to the matrix or directly to earlier colonists. It is during this colonization that the cells are able to communicate via quorum sensing. Once colonization has begun, the biofilm grows through a combination of cell division and recruitment. The final stage of biofilm formation is known as development, and is the stage in which the biofilm is established and may only change in shape and size. This development of biofilm allows for the cells to become more antibiotic resistant.
# Properties
Biofilms are usually found on solid substrates submerged in or exposed to some aqueous solution, although they can form as floating mats on liquid surfaces and also on the surface of leaves, particularly in high humidity climates. Given sufficient resources for growth, a biofilm will quickly grow to be macroscopic. Biofilms can contain many different types of microorganism, e.g. bacteria, archaea, protozoa, fungi and algae; each group performing specialized metabolic functions. However, some organisms will form monospecies films under certain conditions.
## Extracellular matrix
The biofilm is held together and protected by a matrix of excreted polymeric compounds called EPS. EPS is an abbreviation for either extracellular polymeric substance or exopolysaccharide. This matrix protects the cells within it and facilitates communication among them through biochemical signals. Some biofilms have been found to contain water channels that help distribute nutrients and signalling molecules. This matrix is strong enough that under certain conditions, biofilms can become fossilized.
Bacteria living in a biofilm usually have significantly different properties from free-floating bacteria of the same species, as the dense and protected environment of the film allows them to cooperate and interact in various ways.
One benefit of this environment is increased resistance to detergents and antibiotics, as the dense extracellular matrix and the outer layer of cells protect the interior of the community. In some cases antibiotic resistance can be increased 1000 fold.
# Examples
Biofilms are ubiquitous. Nearly every species of microorganism, not only bacteria and archaea, have mechanisms by which they can adhere to surfaces and to each other.
- Biofilms can be found on rocks and pebbles at the bottom of most streams or rivers and often form on the surface of stagnant pools of water. In fact, biofilms are important components of foodchains in rivers and streams and are grazed by the aquatic invertebrates upon which many fish feed.
- Biofilms grow in hot, acidic pools in Yellowstone National Park (USA) and on glaciers in Antarctica.
- In industrial environments, biofilms can develop on the interiors of pipes, which can lead to clogging and corrosion. Biofilms on floors and counters can make sanitation difficult in food preparation areas. Biofilms in cooling water systems are known to reduce heat transfer and harbour Legionella bacteria.
- Biofilms can also be harnessed for constructive purposes. For example, many sewage treatment plants include a treatment stage in which waste water passes over biofilms grown on filters, which extract and digest organic compounds. In such biofilms, bacteria are mainly responsible for removal of organic matter (BOD); whilst protozoa and rotifers are mainly responsible for removal of suspended solids (SS), including pathogens and other microorganisms. Slow sand filters rely on biofilm development in the same way to filter surface water from lake, spring or river sources for drinking purposes.
- Biofilms can help eliminate petroleum oil from contaminated oceans or marine systems. The oil is eliminated by the hydrocarbon-degrading activities of microbial communities, in particular by a remarkable recently discovered group of specialists, the so-called hydrocarbonoclastic bacteria (HCB).
- Biofilms are also present on the teeth of most animals as dental plaque, where they may become responsible for tooth decay and gum disease.
# Biofilms and infectious diseases
Biofilms have been found to be involved in a wide variety of microbial infections in the body, by one estimate 80% of all infections. Infectious processes in which biofilms have been implicated include common problems such as urinary tract infections, catheter infections, middle-ear infections, formation of dental plaque, gingivitis, coating contact lenses, and less common but more lethal processes such as endocarditis, infections in cystic fibrosis, and infections of permanent indwelling devices such as joint prostheses and heart valves.
It has recently been shown that biofilms are present on the removed tissue of 80% of patients undergoing surgery for chronic sinusitis. The patients with biofilms were shown to have been denuded of cilia and goblet cells, unlike the controls without biofilms who had normal cilia and goblet cell morphology. Biofilms were also found on samples from two of 10 healthy controls mentioned. The species of bacteria from interoperative cultures did not correspond to the bacteria species in the biofilm on the respective patient's tissue. In other words, the cultures were negative though the bacteria were present.
New staining techniques are being developed to differentiate bacterial cells growing in living animals, e.g. from tissues with allergy-inflammations .
## Pseudomonas aeruginosa biofilms
The achievements of medical care in industrialised societies are markedly impaired due to chronic opportunistic infections that have become increasingly apparent in immunocompromised patients and the aging population. Chronic infections remain a major challenge for the medical profession and are of great economic relevance because traditional antibiotic therapy is usually not sufficient to eradicate these infections. One major reason for persistence seems to be the capability of the bacteria to grow within biofilms that protects them from adverse environmental factors. Pseudomonas aeruginosa is not only an important opportunistic pathogen and causative agent of emerging nosocomial infections but can also be considered a model organism for the study of diverse bacterial mechanisms that contribute to bacterial persistence. In this context the elucidation of the molecular mechanisms responsible for the switch from planctonic growth to a biofilm phenotype and the role of inter-bacterial communication in persistent disease should provide new insights in P. aeruginosa pathogenicity, contribute to a better clinical management of chronically infected patients and should lead to the identification of new drug targets for the development of alternative anti-infective treatment strategies.
### Dental plaque
Dental plaque is the material that adheres to the teeth and consists of bacterial cells (mainly Streptococcus mutans and Streptococcus sanguis), salivary polymers and bacterial extracellular products. Plaque is a biofilm on the surfaces of the teeth. This accumulation of microorganisms subject the teeth and gingival tissues to high concentrations of bacterial metabolites which results in dental disease. | Biofilm
# Overview
A biofilm is a complex aggregation of microorganisms marked by the excretion of a protective and adhesive matrix. Biofilms are also often characterized by surface attachment, structural heterogeneity, genetic diversity, complex community interactions, and an extracellular matrix of polymeric substances.
Single-celled organisms generally exhibit two distinct modes of behavior. The first is the familiar free floating, or planktonic, form in which single cells float or swim independently in some liquid medium. The second is an attached state in which cells are closely packed and firmly attached to each other and usually form a solid surface. A change in behavior is triggered by many factors, including quorum sensing, as well as other mechanisms that vary between species. When a cell switches modes, it undergoes a phenotypic shift in behavior in which large suites of genes are up- and down- regulated.
# Formation
Formation of a biofilm begins with the attachment of free-floating microorganisms to a surface. These first colonists adhere to the surface initially through weak, reversible van der Waals forces. If the colonists are not immediately separated from the surface, they can anchor themselves more permanently using cell adhesion molecules such as pili.[1]
The first colonists facilitate the arrival of other cells by providing more diverse adhesion sites and beginning to build the matrix that holds the biofilm together. Some species are not able to attach to a surface on their own but are often able to anchor themselves to the matrix or directly to earlier colonists. It is during this colonization that the cells are able to communicate via quorum sensing. Once colonization has begun, the biofilm grows through a combination of cell division and recruitment. The final stage of biofilm formation is known as development, and is the stage in which the biofilm is established and may only change in shape and size. This development of biofilm allows for the cells to become more antibiotic resistant.
# Properties
Biofilms are usually found on solid substrates submerged in or exposed to some aqueous solution, although they can form as floating mats on liquid surfaces and also on the surface of leaves, particularly in high humidity climates. Given sufficient resources for growth, a biofilm will quickly grow to be macroscopic. Biofilms can contain many different types of microorganism, e.g. bacteria, archaea, protozoa, fungi and algae; each group performing specialized metabolic functions. However, some organisms will form monospecies films under certain conditions.
## Extracellular matrix
The biofilm is held together and protected by a matrix of excreted polymeric compounds called EPS. EPS is an abbreviation for either extracellular polymeric substance or exopolysaccharide. This matrix protects the cells within it and facilitates communication among them through biochemical signals. Some biofilms have been found to contain water channels that help distribute nutrients and signalling molecules. This matrix is strong enough that under certain conditions, biofilms can become fossilized.
Bacteria living in a biofilm usually have significantly different properties from free-floating bacteria of the same species, as the dense and protected environment of the film allows them to cooperate and interact in various ways.
One benefit of this environment is increased resistance to detergents and antibiotics, as the dense extracellular matrix and the outer layer of cells protect the interior of the community. In some cases antibiotic resistance can be increased 1000 fold.[2]
# Examples
Biofilms are ubiquitous. Nearly every species of microorganism, not only bacteria and archaea, have mechanisms by which they can adhere to surfaces and to each other.
- Biofilms can be found on rocks and pebbles at the bottom of most streams or rivers and often form on the surface of stagnant pools of water. In fact, biofilms are important components of foodchains in rivers and streams and are grazed by the aquatic invertebrates upon which many fish feed.
- Biofilms grow in hot, acidic pools in Yellowstone National Park (USA) and on glaciers in Antarctica.
- In industrial environments, biofilms can develop on the interiors of pipes, which can lead to clogging and corrosion. Biofilms on floors and counters can make sanitation difficult in food preparation areas. Biofilms in cooling water systems are known to reduce heat transfer[3] and harbour Legionella bacteria[4].
- Biofilms can also be harnessed for constructive purposes. For example, many sewage treatment plants include a treatment stage in which waste water passes over biofilms grown on filters, which extract and digest organic compounds. In such biofilms, bacteria are mainly responsible for removal of organic matter (BOD); whilst protozoa and rotifers are mainly responsible for removal of suspended solids (SS), including pathogens and other microorganisms. Slow sand filters rely on biofilm development in the same way to filter surface water from lake, spring or river sources for drinking purposes.
- Biofilms can help eliminate petroleum oil from contaminated oceans or marine systems. The oil is eliminated by the hydrocarbon-degrading activities of microbial communities, in particular by a remarkable recently discovered group of specialists, the so-called hydrocarbonoclastic bacteria (HCB).[5]
- Biofilms are also present on the teeth of most animals as dental plaque, where they may become responsible for tooth decay and gum disease.
# Biofilms and infectious diseases
Biofilms have been found to be involved in a wide variety of microbial infections in the body, by one estimate 80% of all infections.[6] Infectious processes in which biofilms have been implicated include common problems such as urinary tract infections, catheter infections, middle-ear infections, formation of dental plaque[7], gingivitis[7], coating contact lenses[8], and less common but more lethal processes such as endocarditis, infections in cystic fibrosis, and infections of permanent indwelling devices such as joint prostheses and heart valves.[9][10]
It has recently been shown that biofilms are present on the removed tissue of 80% of patients undergoing surgery for chronic sinusitis. The patients with biofilms were shown to have been denuded of cilia and goblet cells, unlike the controls without biofilms who had normal cilia and goblet cell morphology.[11] Biofilms were also found on samples from two of 10 healthy controls mentioned. The species of bacteria from interoperative cultures did not correspond to the bacteria species in the biofilm on the respective patient's tissue. In other words, the cultures were negative though the bacteria were present.[12]
New staining techniques are being developed to differentiate bacterial cells growing in living animals, e.g. from tissues with allergy-inflammations .[13]
## Pseudomonas aeruginosa biofilms
The achievements of medical care in industrialised societies are markedly impaired due to chronic opportunistic infections that have become increasingly apparent in immunocompromised patients and the aging population. Chronic infections remain a major challenge for the medical profession and are of great economic relevance because traditional antibiotic therapy is usually not sufficient to eradicate these infections. One major reason for persistence seems to be the capability of the bacteria to grow within biofilms that protects them from adverse environmental factors. Pseudomonas aeruginosa is not only an important opportunistic pathogen and causative agent of emerging nosocomial infections but can also be considered a model organism for the study of diverse bacterial mechanisms that contribute to bacterial persistence. In this context the elucidation of the molecular mechanisms responsible for the switch from planctonic growth to a biofilm phenotype and the role of inter-bacterial communication in persistent disease should provide new insights in P. aeruginosa pathogenicity, contribute to a better clinical management of chronically infected patients and should lead to the identification of new drug targets for the development of alternative anti-infective treatment strategies.[14]
### Dental plaque
Dental plaque is the material that adheres to the teeth and consists of bacterial cells (mainly Streptococcus mutans and Streptococcus sanguis), salivary polymers and bacterial extracellular products. Plaque is a biofilm on the surfaces of the teeth. This accumulation of microorganisms subject the teeth and gingival tissues to high concentrations of bacterial metabolites which results in dental disease.[7] | https://www.wikidoc.org/index.php/Biofilm | |
df24d015a4a561742e9b9890b57803a634a82263 | wikidoc | Biology | Biology
Biology (from Greek βιολογία - βίος, bio, "life"; and λόγος, logos, "speech" lit. "to talk about life"), is a branch of Natural Science, and is the study of living organisms and how they react to their environment. Biology deals with every aspect of life in a living organism. Biology examines the structure, function, growth, origin, evolution, and distribution of living things. It classifies and describes organisms, their functions, how species come into existence, and the interactions they have with each other and with the natural environment. Four unifying principles form the foundation of modern biology: cell theory, evolution, genetics and homeostasis.
Biology as a separate science was developed in the nineteenth century as scientists discovered that organisms shared fundamental characteristics. Biology is now a standard subject of instruction at schools and universities around the world, and over a million papers are published annually in a wide array of biology and medicine journals.
Most biological sciences are specialized disciplines. Traditionally, they are grouped by the type of organism being studied: botany, the study of plants; zoology, the study of animals; and microbiology, the study of microorganisms. The fields within biology are further divided based on the scale at which organisms are studied and the methods used to study them: biochemistry examines the fundamental chemistry of life; molecular biology studies the complex interactions of systems of biological molecules; cellular biology examines the basic building block of all life, the cell; physiology examines the physical and chemical functions of the tissues and organ systems of an organism; and ecology examines how various organisms and their environment interrelate.
# Foundations of modern biology
There are five unifying principles of biology :
- Cell theory. Cell Theory is the study of everything that involves cells.All living organisms are made of at least one cell, the basic unit of function in all organisms. In addition, the core mechanisms and chemistry of all cells in all organisms are similar, and cells emerge only from preexisting cells that multiply through cell division. The study of cell theory will tell you how cells are made, how they reproduce, how they interact with their environment, what it is composed of, and how the materials that make up a cell work and there interaction with the other sections of the cells.
- Evolution. Through natural selection and genetic drift, a population's inherited traits change from generation to generation.
- Gene theory. A living organism's traits are encoded in DNA, the fundamental component of genes. In addition, traits are passed on from one generation to the next by way of these genes. All information flows from the genotype to the phenotype, the observable physical or biochemical characteristics of the organism. Although the phenotype expressed by the gene may adapt to the environment of the organism, that information is not transferred back to the genes. Only through the process of evolution do genes change in response to the environment.
- Homeostasis. The physiological processes that allow an organism to maintain its internal environment notwithstanding its external environment.
- Behavior. All living organisms exhibit a stimulus-response behavior.
## Cell Theory
The cell is the fundamental unit of life. Cell theory states that all living things are composed of one or more cells, or the secreted products of those cells, for example, shell and bone. Cells arise from other cells through cell division, and in multicellular organisms, every cell in the organism's body is produced from a single cell in a fertilized egg. Furthermore, the cell is considered to be the basic part of the pathological processes of an organism.
## Evolution
A central organizing concept in biology is that life changes and develops through evolution and that all lifeforms known have a common origin (see Common descent). This has led to the striking similarity of units and processes discussed in the previous section. Introduced into the scientific lexicon by Jean-Baptiste de Lamarck in 1809,Charles Darwin established evolution fifty years later as a viable theory by articulating its driving force, natural selection (Alfred Russel Wallace is recognized as the co-discoverer of this concept as he helped research and experiment with the concept of evolution). Darwin theorized that species and breeds developed through the processes of natural selection as well as by artificial selection or selective breeding. Genetic drift was embraced as an additional mechanism of evolutionary development in the modern synthesis of the theory.
The evolutionary history of the species— which describes the characteristics of the various species from which it descended— together with its genealogical relationship to every other species is called its phylogeny. Widely varied approaches to biology generate information about phylogeny. These include the comparisons of DNA sequences conducted within molecular biology or genomics, and comparisons of fossils or other records of ancient organisms in paleontology. Biologists organize and analyze evolutionary relationships through various methods, including phylogenetics, phenetics, and cladistics. For a summary of major events in the evolution of life as currently understood by biologists, see evolutionary timeline.
Up into the 19th century, it was commonly believed that life forms could appear spontaneously under certain conditions (see spontaneous generation). This misconception was challenged by William Harvey's diction that "all life from egg" (from the Latin "Omne vivum ex ovo"), a foundational concept of modern biology. It simply means that there is an unbroken continuity of life from its initial origin to the present time.
A group of organisms share a common descent if they share a common ancestor. All organisms on the Earth both living and extinct have been or are descended from a common ancestor or an ancestral gene pool. This last universal common ancestor of all organisms is believed to have appeared about 3.5 billion years ago. Biologists generally regard the universality of the genetic code as definitive evidence in favor of the theory of universal common descent (UCD) for all bacteria, archaea, and eukaryotes (see: origin of life).
Evolution does not always give rise to progressively more complex organisms. For example, the process of dysgenics has been observed among the human population.
## Gene theory
Biological form and function are created from and passed on to the next generation by genes, which are the primary units of inheritance. Physiological adaptation to an organism's environment cannot be coded into its genes and cannot be inherited by its offspring (see Lamarckism). Remarkably, widely different organisms, including bacteria, plants, animals, and fungi, all share the same basic machinery that copies and transcribes DNA into proteins. For example, bacteria with inserted human DNA will correctly yield the corresponding human protein.
The total complement of genes in an organism or cell is known as its genome, which is stored on one or more chromosomes. A chromosome is a single, long DNA strand on which thousands of genes, depending on the organism, are encoded. When a gene is active, the DNA code is transcribed into an RNA copy of the gene's information. A ribosome then translates the RNA into a structural protein or catalytic protein.
## Homeostasis
Homeostasis is the ability of an open system to regulate its internal environment to maintain a stable condition by means of multiple dynamic equilibrium adjustments controlled by interrelated regulation mechanisms. All living organisms, whether unicellular or multicellular, exhibit homeostasis. Homeostasis exists at the cellular level, for example cells maintain a stable internal acidity (pH); and at the level of the organism, for example warm-blooded animals maintain a constant internal body temperature. Homeostasis is a term that is also used in association with ecosystems, for example, the atmospheric concentration of carbon dioxide on Earth has been regulated by the concentration of plant life on Earth because plants remove more carbon dioxide from the atmosphere during the daylight hours than they emit to the atmosphere at night. Tissues and organs can also maintain homeostasis.
Punnent Square made by Reginald Punnet in 1905 which is the shorthand way to show the expressed trait
See also: Health.
# Research
## Structural
Molecular biology is the study of biology at a molecular level. This field overlaps with other areas of biology, particularly with genetics and biochemistry. Molecular biology chiefly concerns itself with understanding the interactions between the various systems of a cell, including the interrelationship of DNA, RNA, and protein synthesis and learning how these interactions are regulated.
Cell biology studies the physiological properties of cells, as well as their behaviors, interactions, and environment. This is done both on a microscopic and molecular level. Cell biology researches both single-celled organisms like bacteria and specialized cells in multicellular organisms like humans.
Understanding cell composition and how they function is fundamental to all of the biological sciences. Appreciating the similarities and differences between cell types is particularly important in the fields of cell and molecular biology. These fundamental similarities and differences provide a unifying theme, allowing the principles learned from studying one cell type to be extrapolated and generalized to other cell types.
Genetics is the science of genes, heredity, and the variation of organisms. Genes encode the information necessary for synthesizing proteins, which in turn play a large role in influencing (though, in many instances, not completely determining) the final phenotype of the organism. In modern research, genetics provides important tools in the investigation of the function of a particular gene, or the analysis of genetic interactions. Within organisms, genetic information generally is carried in chromosomes, where it is represented in the chemical structure of particular DNA molecules.
Developmental biology studies the process by which organisms grow and develop. Originating in embryology, modern developmental biology studies the genetic control of cell growth, differentiation, and "morphogenesis," which is the process that gives rise to tissues, organs, and anatomy.
Model organisms for developmental biology include the round worm Caenorhabditis elegans, the fruit fly Drosophila melanogaster, the zebrafish Brachydanio rerio, the mouse Mus musculus, and the weed Arabidopsis thaliana.
## Physiological
Physiology studies the mechanical, physical, and biochemical processes of living organisms by attempting to understand how all of the structures function as a whole. The theme of "structure to function" is central to biology. Physiological studies have traditionally been divided into plant physiology and animal physiology, but the principles of physiology are universal, no matter what particular organism is being studied. For example, what is learned about the physiology of yeast cells can also apply to human cells. The field of animal physiology extends the tools and methods of human physiology to non-human species. Plant physiology also borrows techniques from both fields.
Anatomy is an important branch of physiology and considers how organ systems in animals, such as the nervous, immune, endocrine, respiratory, and circulatory systems, function and interact. The study of these systems is shared with medically oriented disciplines such as neurology and immunology.
## Evolution
Evolution is concerned with the origin and descent of species, as well as their change over time, and includes scientists from many taxonomically-oriented disciplines. For example, it generally involves scientists who have special training in particular organisms such as mammalogy, ornithology, botany, or herpetology, but use those organisms as systems to answer general questions about evolution. Evolutionary biology is mainly based on paleontology, which uses the fossil record to answer questions about the mode and tempo of evolution, as well as the developments in areas such as population genetics and evolutionary theory. In the 1980s, developmental biology re-entered evolutionary biology from its initial exclusion from the modern synthesis through the study of evolutionary developmental biology. Related fields which are often considered part of evolutionary biology are phylogenetics, systematics, and taxonomy.
Up into the 19th century, it was believed that life forms were being continuously created under certain conditions (see spontaneous generation). This misconception was challenged by William Harvey's diction that "all life from egg" (from the Latin "Omne vivum ex ovo"), a foundational concept of modern biology. It simply means that there is an unbroken continuity of life from its initial origin to the present time.
A group of organisms shares a common descent if they share a common ancestor. All organisms on the Earth have been and are descended from a common ancestor or an ancestral gene pool. This last universal common ancestor of all organisms is believed to have appeared about 3.5 billion years ago. Biologists generally regard the universality of the genetic code as definitive evidence in favor of the theory of universal common descent (UCD) for all bacteria, archaea, and eukaryotes (see: origin of life).
The two major traditional taxonomically-oriented disciplines are botany and zoology. Botany is the scientific study of plants. Botany covers a wide range of scientific disciplines that study the growth, reproduction, metabolism, development, diseases, and evolution of plant life. Zoology involves the study of animals, including the study of their physiology within the fields of anatomy and embryology. The common genetic and developmental mechanisms of animals and plants is studied in molecular biology, molecular genetics, and developmental biology. The ecology of animals is covered under behavioral ecology and other fields.
## Taxonomy
Classification is the province of the disciplines of systematics and taxonomy. Taxonomy places organisms in groups called taxa, while systematics seeks to define their relationships with each other. This classification technique has evolved to reflect advances in cladistics and genetics, shifting the focus from physical similarities and shared characteristics to phylogenetics.
Traditionally, living things have been divided into five kingdoms:
However, many scientists now consider this five-kingdom system to be outdated. Modern alternative classification systems generally begin with the three-domain system:
These domains reflect whether the cells have nuclei or not, as well as differences in the cell exteriors.
Further, each kingdom is broken down continuously until each species is separately classified. The order is:
- Domain
- Kingdom
- Phylum
- Class
- Order
- Family
- Genus
- Species
The scientific name of an organism is obtained from its genus and species. For example, humans would be listed as Homo sapiens. Homo would be the genus and sapiens is the species. Whenever writing the scientific name of an organism, it is proper to capitalize the first letter in the genus and put all of the species in lowercase; in addition the entire term would be put in italics or underlined. The term used for classification is called taxonomy.
There is also a series of intracellular parasites that are progressively "less alive" in terms of metabolic activity:
The dominant classification system is called Linnaean taxonomy, which includes ranks and binomial nomenclature. How organisms are named is governed by international agreements such as the International Code of Botanical Nomenclature (ICBN), the International Code of Zoological Nomenclature (ICZN), and the International Code of Nomenclature of Bacteria (ICNB). A fourth Draft BioCode was published in 1997 in an attempt to standardize naming in these three areas, but it has yet to be formally adopted. The Virus International Code of Virus Classification and Nomenclature (ICVCN) remains outside the BioCode.
## Environmental
Ecology studies the distribution and abundance of living organisms, and the interactions between organisms and their environment. The environment of an organism includes both its habitat, which can be described as the sum of local abiotic factors such as climate and ecology, as well as the other organisms that share its habitat. Ecological systems are studied at several different levels, from individuals and populations to ecosystems and the biosphere. As can be surmised, ecology is a science that draws on several disciplines.
Ethology studies animal behavior (particularly of social animals such as primates and canids), and is sometimes considered a branch of zoology. Ethologists have been particularly concerned with the evolution of behavior and the understanding of behavior in terms of the theory of natural selection. In one sense, the first modern ethologist was Charles Darwin, whose book "The Expression of the Emotions in Man and Animals" influenced many ethologists.
Biogeography studies the spatial distribution of organisms on the Earth, focusing on topics like plate tectonics, climate change, dispersal and migration, and cladistics.
Every living thing interacts with other organisms and its environment. One reason that biological systems can be difficult to study is that so many different interactions with other organisms and the environment are possible, even on the smallest of scales. A microscopic bacterium responding to a local sugar gradient is responding to its environment as much as a lion is responding to its environment when it searches for food in the African savannah. For any given species, behaviors can be co-operative, aggressive, parasitic or symbiotic. Matters become more complex when two or more different species interact in an ecosystem. Studies of this type are the province of ecology.
# History
Although the concept of biology as a single coherent field arose in the 19th century, the biological sciences emerged from traditions of medicine and natural history reaching back to Galen and Aristotle in the ancient Greco-Roman world, which were then further developed in the Middle Ages by Muslim physicians such as al-Jahiz, Avicenna, Avenzoar and Ibn al-Nafis. During the European Renaissance and early modern period, biological thought was revolutionized in Europe by a renewed interest in empiricism and the discovery of many novel organisms. Prominent in this movement were Vesalius and Harvey, who used experimentation and careful observation in physiology, and naturalists such as Linnaeus and Buffon who began to classify the diversity of life and the fossil record, as well as the development and behavior of organisms. Microscopy revealed the previously unknown world of microorganisms, laying the groundwork for cell theory. The growing importance of natural theology, partly a response to the rise of mechanical philosophy, encouraged the growth of natural history.
Over the 18th and 19th centuries, biological sciences such as botany and zoology became increasingly professional scientific disciplines. Lavoisier and other physical scientists began to connect the animate and inanimate worlds through physics and chemistry. Explorer-naturalists such as Alexander von Humboldt investigated the interaction between organisms and their environment, and the ways this relationship depends on geography—laying the foundations for biogeography, ecology and ethology. Naturalists began to reject essentialism and consider the importance of extinction and the mutability of species. Cell theory provided a new perspective on the fundamental basis of life. These developments, as well as the results from embryology and paleontology, were synthesized in Charles Darwins theory of evolution by natural selection. The end of the 19th century saw the fall of spontaneous generation and the rise of the germ theory of disease, though the mechanism of inheritance remained a mystery.
In the early 20th century, the rediscovery of Mendel's work led to the rapid development of genetics by Thomas Hunt Morgan and his students, and by the 1930s the combination of population genetics and natural selection in the "neo-Darwinian synthesis". New disciplines developed rapidly, especially after Watson and Crick proposed the structure of DNA. Following the establishment of the Central Dogma and the cracking of the genetic code, biology was largely split between organismal biology—the fields that deal with whole organisms and groups of organisms—and the fields related to cellular and molecular biology. By the late 20th century, new fields like genomics and proteomics were reversing this trend, with organismal biologists using molecular techniques, and molecular and cell biologists investigating the interplay between genes and the environment, as well as the genetics of natural populations of organisms. | Biology
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Biology (from Greek βιολογία - βίος, bio, "life"; and λόγος, logos, "speech" lit. "to talk about life"), is a branch of Natural Science, and is the study of living organisms and how they react to their environment. Biology deals with every aspect of life in a living organism. Biology examines the structure, function, growth, origin, evolution, and distribution of living things. It classifies and describes organisms, their functions, how species come into existence, and the interactions they have with each other and with the natural environment. Four unifying principles form the foundation of modern biology: cell theory, evolution, genetics and homeostasis.
Biology as a separate science was developed in the nineteenth century as scientists discovered that organisms shared fundamental characteristics. Biology is now a standard subject of instruction at schools and universities around the world, and over a million papers are published annually in a wide array of biology and medicine journals.[1]
Most biological sciences are specialized disciplines. Traditionally, they are grouped by the type of organism being studied: botany, the study of plants; zoology, the study of animals; and microbiology, the study of microorganisms. The fields within biology are further divided based on the scale at which organisms are studied and the methods used to study them: biochemistry examines the fundamental chemistry of life; molecular biology studies the complex interactions of systems of biological molecules; cellular biology examines the basic building block of all life, the cell; physiology examines the physical and chemical functions of the tissues and organ systems of an organism; and ecology examines how various organisms and their environment interrelate.
# Foundations of modern biology
There are five unifying principles of biology [2]:
- Cell theory. Cell Theory is the study of everything that involves cells.All living organisms are made of at least one cell, the basic unit of function in all organisms. In addition, the core mechanisms and chemistry of all cells in all organisms are similar, and cells emerge only from preexisting cells that multiply through cell division. The study of cell theory will tell you how cells are made, how they reproduce, how they interact with their environment, what it is composed of, and how the materials that make up a cell work and there interaction with the other sections of the cells.
- Evolution. Through natural selection and genetic drift, a population's inherited traits change from generation to generation.
- Gene theory. A living organism's traits are encoded in DNA, the fundamental component of genes. In addition, traits are passed on from one generation to the next by way of these genes. All information flows from the genotype to the phenotype, the observable physical or biochemical characteristics of the organism. Although the phenotype expressed by the gene may adapt to the environment of the organism, that information is not transferred back to the genes. Only through the process of evolution do genes change in response to the environment.
- Homeostasis. The physiological processes that allow an organism to maintain its internal environment notwithstanding its external environment.
- Behavior. All living organisms exhibit a stimulus-response behavior.
## Cell Theory
The cell is the fundamental unit of life. Cell theory states that all living things are composed of one or more cells, or the secreted products of those cells, for example, shell and bone. Cells arise from other cells through cell division, and in multicellular organisms, every cell in the organism's body is produced from a single cell in a fertilized egg. Furthermore, the cell is considered to be the basic part of the pathological processes of an organism.[3]
## Evolution
A central organizing concept in biology is that life changes and develops through evolution and that all lifeforms known have a common origin (see Common descent). This has led to the striking similarity of units and processes discussed in the previous section. Introduced into the scientific lexicon by Jean-Baptiste de Lamarck in 1809,Charles Darwin established evolution fifty years later as a viable theory by articulating its driving force, natural selection (Alfred Russel Wallace is recognized as the co-discoverer of this concept as he helped research and experiment with the concept of evolution). Darwin theorized that species and breeds developed through the processes of natural selection as well as by artificial selection or selective breeding.[4] Genetic drift was embraced as an additional mechanism of evolutionary development in the modern synthesis of the theory.
The evolutionary history of the species— which describes the characteristics of the various species from which it descended— together with its genealogical relationship to every other species is called its phylogeny. Widely varied approaches to biology generate information about phylogeny. These include the comparisons of DNA sequences conducted within molecular biology or genomics, and comparisons of fossils or other records of ancient organisms in paleontology. Biologists organize and analyze evolutionary relationships through various methods, including phylogenetics, phenetics, and cladistics. For a summary of major events in the evolution of life as currently understood by biologists, see evolutionary timeline.
Up into the 19th century, it was commonly believed that life forms could appear spontaneously under certain conditions (see spontaneous generation). This misconception was challenged by William Harvey's diction that "all life [is] from [an] egg" (from the Latin "Omne vivum ex ovo"), a foundational concept of modern biology. It simply means that there is an unbroken continuity of life from its initial origin to the present time.
A group of organisms share a common descent if they share a common ancestor. All organisms on the Earth both living and extinct have been or are descended from a common ancestor or an ancestral gene pool. This last universal common ancestor of all organisms is believed to have appeared about 3.5 billion years ago. Biologists generally regard the universality of the genetic code as definitive evidence in favor of the theory of universal common descent (UCD) for all bacteria, archaea, and eukaryotes (see: origin of life).
Evolution does not always give rise to progressively more complex organisms. For example, the process of dysgenics has been observed among the human population.[5]
## Gene theory
Biological form and function are created from and passed on to the next generation by genes, which are the primary units of inheritance. Physiological adaptation to an organism's environment cannot be coded into its genes and cannot be inherited by its offspring (see Lamarckism). Remarkably, widely different organisms, including bacteria, plants, animals, and fungi, all share the same basic machinery that copies and transcribes DNA into proteins. For example, bacteria with inserted human DNA will correctly yield the corresponding human protein.
The total complement of genes in an organism or cell is known as its genome, which is stored on one or more chromosomes. A chromosome is a single, long DNA strand on which thousands of genes, depending on the organism, are encoded. When a gene is active, the DNA code is transcribed into an RNA copy of the gene's information. A ribosome then translates the RNA into a structural protein or catalytic protein.
## Homeostasis
Homeostasis is the ability of an open system to regulate its internal environment to maintain a stable condition by means of multiple dynamic equilibrium adjustments controlled by interrelated regulation mechanisms. All living organisms, whether unicellular or multicellular, exhibit homeostasis. Homeostasis exists at the cellular level, for example cells maintain a stable internal acidity (pH); and at the level of the organism, for example warm-blooded animals maintain a constant internal body temperature. Homeostasis is a term that is also used in association with ecosystems, for example, the atmospheric concentration of carbon dioxide on Earth has been regulated by the concentration of plant life on Earth because plants remove more carbon dioxide from the atmosphere during the daylight hours than they emit to the atmosphere at night. Tissues and organs can also maintain homeostasis.
Punnent Square made by Reginald Punnet in 1905 which is the shorthand way to show the expressed trait
See also: Health.
# Research
## Structural
Molecular biology is the study of biology at a molecular level. This field overlaps with other areas of biology, particularly with genetics and biochemistry. Molecular biology chiefly concerns itself with understanding the interactions between the various systems of a cell, including the interrelationship of DNA, RNA, and protein synthesis and learning how these interactions are regulated.
Cell biology studies the physiological properties of cells, as well as their behaviors, interactions, and environment. This is done both on a microscopic and molecular level. Cell biology researches both single-celled organisms like bacteria and specialized cells in multicellular organisms like humans.
Understanding cell composition and how they function is fundamental to all of the biological sciences. Appreciating the similarities and differences between cell types is particularly important in the fields of cell and molecular biology. These fundamental similarities and differences provide a unifying theme, allowing the principles learned from studying one cell type to be extrapolated and generalized to other cell types.
Genetics is the science of genes, heredity, and the variation of organisms. Genes encode the information necessary for synthesizing proteins, which in turn play a large role in influencing (though, in many instances, not completely determining) the final phenotype of the organism. In modern research, genetics provides important tools in the investigation of the function of a particular gene, or the analysis of genetic interactions. Within organisms, genetic information generally is carried in chromosomes, where it is represented in the chemical structure of particular DNA molecules.
Developmental biology studies the process by which organisms grow and develop. Originating in embryology, modern developmental biology studies the genetic control of cell growth, differentiation, and "morphogenesis," which is the process that gives rise to tissues, organs, and anatomy.
Model organisms for developmental biology include the round worm Caenorhabditis elegans, the fruit fly Drosophila melanogaster, the zebrafish Brachydanio rerio, the mouse Mus musculus, and the weed Arabidopsis thaliana.
## Physiological
Physiology studies the mechanical, physical, and biochemical processes of living organisms by attempting to understand how all of the structures function as a whole. The theme of "structure to function" is central to biology. Physiological studies have traditionally been divided into plant physiology and animal physiology, but the principles of physiology are universal, no matter what particular organism is being studied. For example, what is learned about the physiology of yeast cells can also apply to human cells. The field of animal physiology extends the tools and methods of human physiology to non-human species. Plant physiology also borrows techniques from both fields.
Anatomy is an important branch of physiology and considers how organ systems in animals, such as the nervous, immune, endocrine, respiratory, and circulatory systems, function and interact. The study of these systems is shared with medically oriented disciplines such as neurology and immunology.
## Evolution
Evolution is concerned with the origin and descent of species, as well as their change over time, and includes scientists from many taxonomically-oriented disciplines. For example, it generally involves scientists who have special training in particular organisms such as mammalogy, ornithology, botany, or herpetology, but use those organisms as systems to answer general questions about evolution. Evolutionary biology is mainly based on paleontology, which uses the fossil record to answer questions about the mode and tempo of evolution, as well as the developments in areas such as population genetics and evolutionary theory. In the 1980s, developmental biology re-entered evolutionary biology from its initial exclusion from the modern synthesis through the study of evolutionary developmental biology. Related fields which are often considered part of evolutionary biology are phylogenetics, systematics, and taxonomy.
Up into the 19th century, it was believed that life forms were being continuously created under certain conditions (see spontaneous generation). This misconception was challenged by William Harvey's diction that "all life [is] from [an] egg" (from the Latin "Omne vivum ex ovo"), a foundational concept of modern biology. It simply means that there is an unbroken continuity of life from its initial origin to the present time.
A group of organisms shares a common descent if they share a common ancestor. All organisms on the Earth have been and are descended from a common ancestor or an ancestral gene pool. This last universal common ancestor of all organisms is believed to have appeared about 3.5 billion years ago. Biologists generally regard the universality of the genetic code as definitive evidence in favor of the theory of universal common descent (UCD) for all bacteria, archaea, and eukaryotes (see: origin of life).
The two major traditional taxonomically-oriented disciplines are botany and zoology. Botany is the scientific study of plants. Botany covers a wide range of scientific disciplines that study the growth, reproduction, metabolism, development, diseases, and evolution of plant life. Zoology involves the study of animals, including the study of their physiology within the fields of anatomy and embryology. The common genetic and developmental mechanisms of animals and plants is studied in molecular biology, molecular genetics, and developmental biology. The ecology of animals is covered under behavioral ecology and other fields.[6]
## Taxonomy
Classification is the province of the disciplines of systematics and taxonomy. Taxonomy places organisms in groups called taxa, while systematics seeks to define their relationships with each other. This classification technique has evolved to reflect advances in cladistics and genetics, shifting the focus from physical similarities and shared characteristics to phylogenetics.
Traditionally, living things have been divided into five kingdoms:[7]
However, many scientists now consider this five-kingdom system to be outdated. Modern alternative classification systems generally begin with the three-domain system:[8]
These domains reflect whether the cells have nuclei or not, as well as differences in the cell exteriors.
Further, each kingdom is broken down continuously until each species is separately classified. The order is:
- Domain
- Kingdom
- Phylum
- Class
- Order
- Family
- Genus
- Species
The scientific name of an organism is obtained from its genus and species. For example, humans would be listed as Homo sapiens. Homo would be the genus and sapiens is the species. Whenever writing the scientific name of an organism, it is proper to capitalize the first letter in the genus and put all of the species in lowercase; in addition the entire term would be put in italics or underlined. The term used for classification is called taxonomy.
There is also a series of intracellular parasites that are progressively "less alive" in terms of metabolic activity:
The dominant classification system is called Linnaean taxonomy, which includes ranks and binomial nomenclature. How organisms are named is governed by international agreements such as the International Code of Botanical Nomenclature (ICBN), the International Code of Zoological Nomenclature (ICZN), and the International Code of Nomenclature of Bacteria (ICNB). A fourth Draft BioCode was published in 1997 in an attempt to standardize naming in these three areas, but it has yet to be formally adopted. The Virus International Code of Virus Classification and Nomenclature (ICVCN) remains outside the BioCode.
## Environmental
Ecology studies the distribution and abundance of living organisms, and the interactions between organisms and their environment. The environment of an organism includes both its habitat, which can be described as the sum of local abiotic factors such as climate and ecology, as well as the other organisms that share its habitat. Ecological systems are studied at several different levels, from individuals and populations to ecosystems and the biosphere. As can be surmised, ecology is a science that draws on several disciplines.
Ethology studies animal behavior (particularly of social animals such as primates and canids), and is sometimes considered a branch of zoology. Ethologists have been particularly concerned with the evolution of behavior and the understanding of behavior in terms of the theory of natural selection. In one sense, the first modern ethologist was Charles Darwin, whose book "The Expression of the Emotions in Man and Animals" influenced many ethologists.
Biogeography studies the spatial distribution of organisms on the Earth, focusing on topics like plate tectonics, climate change, dispersal and migration, and cladistics.
Every living thing interacts with other organisms and its environment. One reason that biological systems can be difficult to study is that so many different interactions with other organisms and the environment are possible, even on the smallest of scales. A microscopic bacterium responding to a local sugar gradient is responding to its environment as much as a lion is responding to its environment when it searches for food in the African savannah. For any given species, behaviors can be co-operative, aggressive, parasitic or symbiotic. Matters become more complex when two or more different species interact in an ecosystem. Studies of this type are the province of ecology.
# History
Although the concept of biology as a single coherent field arose in the 19th century, the biological sciences emerged from traditions of medicine and natural history reaching back to Galen and Aristotle in the ancient Greco-Roman world, which were then further developed in the Middle Ages by Muslim physicians such as al-Jahiz,[9] Avicenna,[10] Avenzoar[11] and Ibn al-Nafis.[12] During the European Renaissance and early modern period, biological thought was revolutionized in Europe by a renewed interest in empiricism and the discovery of many novel organisms. Prominent in this movement were Vesalius and Harvey, who used experimentation and careful observation in physiology, and naturalists such as Linnaeus and Buffon who began to classify the diversity of life and the fossil record, as well as the development and behavior of organisms. Microscopy revealed the previously unknown world of microorganisms, laying the groundwork for cell theory. The growing importance of natural theology, partly a response to the rise of mechanical philosophy, encouraged the growth of natural history.[13][14]
Over the 18th and 19th centuries, biological sciences such as botany and zoology became increasingly professional scientific disciplines. Lavoisier and other physical scientists began to connect the animate and inanimate worlds through physics and chemistry. Explorer-naturalists such as Alexander von Humboldt investigated the interaction between organisms and their environment, and the ways this relationship depends on geography—laying the foundations for biogeography, ecology and ethology. Naturalists began to reject essentialism and consider the importance of extinction and the mutability of species. Cell theory provided a new perspective on the fundamental basis of life. These developments, as well as the results from embryology and paleontology, were synthesized in Charles Darwins theory of evolution by natural selection. The end of the 19th century saw the fall of spontaneous generation and the rise of the germ theory of disease, though the mechanism of inheritance remained a mystery.[6][15][13]
In the early 20th century, the rediscovery of Mendel's work led to the rapid development of genetics by Thomas Hunt Morgan and his students, and by the 1930s the combination of population genetics and natural selection in the "neo-Darwinian synthesis". New disciplines developed rapidly, especially after Watson and Crick proposed the structure of DNA. Following the establishment of the Central Dogma and the cracking of the genetic code, biology was largely split between organismal biology—the fields that deal with whole organisms and groups of organisms—and the fields related to cellular and molecular biology. By the late 20th century, new fields like genomics and proteomics were reversing this trend, with organismal biologists using molecular techniques, and molecular and cell biologists investigating the interplay between genes and the environment, as well as the genetics of natural populations of organisms.[16][17][18][19] | https://www.wikidoc.org/index.php/Biologic | |
82e62900adf5115ed79582d6090c6ae41b8b13a0 | wikidoc | Biomass | Biomass
Biomass refers to living and recently dead biological material that can be used as fuel or for industrial production. Most commonly, biomass refers to plant matter grown for use as biofuel, but it also includes plant or animal matter used for production of fibres, chemicals or heat. Biomass may also include biodegradable wastes that can be burnt as fuel. It excludes organic material which has been transformed by geological processes into substances such as coal or petroleum.
Biomass is grown from several plants, including miscanthus, switchgrass, hemp, corn, poplar, willow, sugarcane and oil palm (palm oil). The particular plant used is usually not very important to the end products, but it does affect the processing of the raw material. Production of biomass is a growing industry as interest in sustainable fuel sources is growing.
Although fossil fuels have their origin in ancient biomass, they are not considered biomass by the generally accepted definition because they contain carbon that has been "out" of the carbon cycle for a very long time. Their combustion therefore disturbs the carbon dioxide content in the atmosphere.
Plastics from biomass, like some recently developed to dissolve in seawater, are made the same way as petroleum-based plastics, are actually cheaper to manufacture and meet or exceed most performance standards. But they lack the same water resistance or longevity as conventional plastics.
# Processing and uses
Biomass which is not simply burned as fuel may be processed in other ways such as corn.
Low tech processes include:
- composting (to make soil conditioners and fertilizers)
- anaerobic digestion (decaying biomass to produce methane gas and sludge as a fertilizer)
- fermentation and distillation (both produce ethyl alcohol)
More high-tech processes are:
- Pyrolysis (heating organic wastes in the absence of air to produce gas and char. Both are combustible.)
- Hydrogasification (produces methane and ethane)
- Hydrogenation (converts biomass to oil using carbon monoxide and steam under high pressures and temperatures)
- Destructive distillation (produces methyl alcohol from high cellulose organic wastes).
- Acid hydrolysis (treatment of wood wastes to produce sugars, which can be distilled)
Burning biomass, or the fuel products produced from it, may be used for heat or electricity production.
Other uses of biomass, besides fuel and compost include:
- Building materials
- Biodegradable plastics and paper (using cellulose fibres)
# Environmental impact
Biomass is part of the carbon cycle. Carbon from the atmosphere is converted into biological matter by photosynthesis. On death or combustion the carbon goes back into the atmosphere as carbon dioxide (CO2). This happens over a relatively short timescale and plant matter used as a fuel can be constantly replaced by planting for new growth. Therefore a reasonably stable level of atmospheric carbon results from its use as a fuel. It is commonly accepted that the amount of carbon stored in dry wood is approximately 50% by weight.
Though biomass is a renewable fuel, and is sometimes called a "carbon neutral" fuel, its use can still contribute to global warming. This happens when the natural carbon equilibrium is disturbed; for example by deforestation or urbanization of green sites. When biomass is used as a fuel, as a replacement for fossil fuels, it still puts the same amount of CO2 into the atmosphere. However, when biomass is used for energy production it is widely considered carbon neutral, or a net reducer of greenhouse gasses because of the offset of methane that would have otherwise entered the atmosphere. The carbon in biomass material, which makes up approximately fifty percent of its dry-matter content, is already part of the atmospheric carbon cycle. Biomass absorbs CO2 from the atmosphere during its growing lifetime. After its life, the carbon in biomass recycles to the atmosphere as a mixture of CO2 and methane (CH4), depending on the ultimate fate of the biomass material. CH4 converts to CO2 in the atmosphere, completing the cycle. In contrast to biomass carbon, the carbon in fossil fuels is locked away in geological storage forever, unless extracted. The use of fossil fuels removes carbon from long-term storage, and adds it to the stock of carbon in the atmospheric cycle.
Energy produced from biomass residues displaces the production of an equivalent amount of energy from fossil fuels, leaving the fossil carbon in storage. It also shifts the composition of the recycled carbon emissions associated with the disposal of the biomass residues from a mixture of CO2 and CH4, to almost exclusively CO2. In the absence of energy production applications, biomass residue carbon would be recycled to the atmosphere through some combination of rotting (biodegradation) and opening burning. Rotting produces a mixture of up to fifty percent CH4, while open burning produces five to ten percent CH4. Controlled combustion in a power plant converts virtually all of the carbon in the biomass to CO2. Because CH4 is a much stronger greenhouse gas than CO2, shifting CH4 emissions to CO2 by converting biomass residues to energy significantly reduces the greenhouse warming potential of the recycled carbon associated with other fates or disposal of the biomass residues.
The existing commercial biomass power generating industry in the United States, which consists of approximately 1,700 MW (megawatts) of operating capacity actively supplying power to the grid, produces about 0.5 percent of the U.S. electricity supply. This level of biomass power generation avoids approximately 11 million tons per year of CO2 emissions from fossil fuel combustion. It also avoids approximately two million tons per year of CH4 emissions from the biomass residues that, in the absence of energy production, would otherwise be disposed of by burial (in landfills, in disposal piles, or by the plowing under of agricultural residues), by spreading, and by open burning. The avoided CH4 emissions associated with biomass energy production have a greenhouse warming potential that is more than 20 times greater than that of the avoided fossil-fuel CO2 emissions. Biomass power production is at least five times more effective in reducing greenhouse gas emissions than any other greenhouse-gas-neutral power-production technology, such as other renewables and nuclear.
Currently, the New Hope Power Partnership, owned by Florida Crystals Corporation, is the largest biomass cogeneration energy facility in the U.S. The 140 MWH facility recycles sugar cane fiber and urban wood waste, generating enough electricity to power its large milling and refining operations as well as renewable electricity for more than 40,000 homes. The facility reduces dependence on approximately 800,000 barrels of oil per year and by recycling sugar cane and wood waste, preserves landfill space in urban communities in Florida.
Despite harvesting, biomass crops may sequester (trap) carbon. So for example soil organic carbon has been observed to be greater in switchgrass stands than in cultivated cropland soil, especially at depths below 12 inches. The grass sequesters the carbon in its increased root biomass. But the perennial grass may need to be allowed to grow for several years before increases are measurable.
# Biomass production for human use and consumption
This is a list of estimated biomass for human use and consumption. It does not include biomass which is not harvested or utilised.
Source: Whittaker, R. H. (1975). "The Biosphere and Man". In Leith, H. & Whittaker, R. H. Primary Productivity of the Biosphere. Springer-Verlag. pp. 305–328. ISBN 0-3870-7083-4. Unknown parameter |coauthors= ignored (help)CS1 maint: Multiple names: editors list (link) .mw-parser-output cite.citation{font-style:inherit}.mw-parser-output q{quotes:"\"""\"""'""'"}.mw-parser-output code.cs1-code{color:inherit;background:inherit;border:inherit;padding:inherit}.mw-parser-output .cs1-lock-free a{background:url("")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-limited a,.mw-parser-output .cs1-lock-registration a{background:url("")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-subscription a{background:url("")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration{color:#555}.mw-parser-output .cs1-subscription span,.mw-parser-output .cs1-registration span{border-bottom:1px dotted;cursor:help}.mw-parser-output .cs1-hidden-error{display:none;font-size:100%}.mw-parser-output .cs1-visible-error{display:none;font-size:100%}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration,.mw-parser-output .cs1-format{font-size:95%}.mw-parser-output .cs1-kern-left,.mw-parser-output .cs1-kern-wl-left{padding-left:0.2em}.mw-parser-output .cs1-kern-right,.mw-parser-output .cs1-kern-wl-right{padding-right:0.2em}; Ecological Studies Vol 14 (Berlin)
Darci and Taylre are biomass specialists. | Biomass
Template:Renewable energy sources
Biomass refers to living and recently dead biological material that can be used as fuel or for industrial production. Most commonly, biomass refers to plant matter grown for use as biofuel, but it also includes plant or animal matter used for production of fibres, chemicals or heat. Biomass may also include biodegradable wastes that can be burnt as fuel. It excludes organic material which has been transformed by geological processes into substances such as coal or petroleum.
Biomass is grown from several plants, including miscanthus, switchgrass, hemp, corn, poplar, willow, sugarcane [1] and oil palm (palm oil). The particular plant used is usually not very important to the end products, but it does affect the processing of the raw material. Production of biomass is a growing industry as interest in sustainable fuel sources is growing.[citation needed]
Although fossil fuels have their origin in ancient biomass, they are not considered biomass by the generally accepted definition because they contain carbon that has been "out" of the carbon cycle for a very long time. Their combustion therefore disturbs the carbon dioxide content in the atmosphere.
Plastics from biomass, like some recently developed to dissolve in seawater, are made the same way as petroleum-based plastics, are actually cheaper to manufacture and meet or exceed most performance standards. But they lack the same water resistance or longevity as conventional plastics.[2]
# Processing and uses
Biomass which is not simply burned as fuel may be processed in other ways such as corn.
Low tech processes include:[3]
- composting (to make soil conditioners and fertilizers)
- anaerobic digestion (decaying biomass to produce methane gas and sludge as a fertilizer)
- fermentation and distillation (both produce ethyl alcohol)
More high-tech processes are:
- Pyrolysis (heating organic wastes in the absence of air to produce gas and char. Both are combustible.)
- Hydrogasification (produces methane and ethane)
- Hydrogenation (converts biomass to oil using carbon monoxide and steam under high pressures and temperatures)
- Destructive distillation (produces methyl alcohol from high cellulose organic wastes).
- Acid hydrolysis (treatment of wood wastes to produce sugars, which can be distilled)
Burning biomass, or the fuel products produced from it, may be used for heat or electricity production.
Other uses of biomass, besides fuel and compost include:
- Building materials
- Biodegradable plastics and paper (using cellulose fibres)
# Environmental impact
Biomass is part of the carbon cycle. Carbon from the atmosphere is converted into biological matter by photosynthesis. On death or combustion the carbon goes back into the atmosphere as carbon dioxide (CO2). This happens over a relatively short timescale and plant matter used as a fuel can be constantly replaced by planting for new growth. Therefore a reasonably stable level of atmospheric carbon results from its use as a fuel. It is commonly accepted that the amount of carbon stored in dry wood is approximately 50% by weight.[4]
Though biomass is a renewable fuel, and is sometimes called a "carbon neutral" fuel, its use can still contribute to global warming. This happens when the natural carbon equilibrium is disturbed; for example by deforestation or urbanization of green sites. When biomass is used as a fuel, as a replacement for fossil fuels, it still puts the same amount of CO2 into the atmosphere. However, when biomass is used for energy production it is widely considered carbon neutral, or a net reducer of greenhouse gasses because of the offset of methane that would have otherwise entered the atmosphere. The carbon in biomass material, which makes up approximately fifty percent of its dry-matter content, is already part of the atmospheric carbon cycle. Biomass absorbs CO2 from the atmosphere during its growing lifetime. After its life, the carbon in biomass recycles to the atmosphere as a mixture of CO2 and methane (CH4), depending on the ultimate fate of the biomass material. CH4 converts to CO2 in the atmosphere, completing the cycle. In contrast to biomass carbon, the carbon in fossil fuels is locked away in geological storage forever, unless extracted. The use of fossil fuels removes carbon from long-term storage, and adds it to the stock of carbon in the atmospheric cycle.
Energy produced from biomass residues displaces the production of an equivalent amount of energy from fossil fuels, leaving the fossil carbon in storage. It also shifts the composition of the recycled carbon emissions associated with the disposal of the biomass residues from a mixture of CO2 and CH4, to almost exclusively CO2. In the absence of energy production applications, biomass residue carbon would be recycled to the atmosphere through some combination of rotting (biodegradation) and opening burning. Rotting produces a mixture of up to fifty percent CH4, while open burning produces five to ten percent CH4. Controlled combustion in a power plant converts virtually all of the carbon in the biomass to CO2. Because CH4 is a much stronger greenhouse gas than CO2, shifting CH4 emissions to CO2 by converting biomass residues to energy significantly reduces the greenhouse warming potential of the recycled carbon associated with other fates or disposal of the biomass residues.
The existing commercial biomass power generating industry in the United States, which consists of approximately 1,700 MW (megawatts) of operating capacity actively supplying power to the grid, produces about 0.5 percent of the U.S. electricity supply. This level of biomass power generation avoids approximately 11 million tons per year of CO2 emissions from fossil fuel combustion. It also avoids approximately two million tons per year of CH4 emissions from the biomass residues that, in the absence of energy production, would otherwise be disposed of by burial (in landfills, in disposal piles, or by the plowing under of agricultural residues), by spreading, and by open burning. The avoided CH4 emissions associated with biomass energy production have a greenhouse warming potential that is more than 20 times greater than that of the avoided fossil-fuel CO2 emissions. Biomass power production is at least five times more effective in reducing greenhouse gas emissions than any other greenhouse-gas-neutral power-production technology, such as other renewables and nuclear. [5]
Currently, the New Hope Power Partnership, owned by Florida Crystals Corporation, is the largest biomass cogeneration energy facility in the U.S. The 140 MWH facility recycles sugar cane fiber and urban wood waste, generating enough electricity to power its large milling and refining operations as well as renewable electricity for more than 40,000 homes. The facility reduces dependence on approximately 800,000 barrels of oil per year and by recycling sugar cane and wood waste, preserves landfill space in urban communities in Florida.
[6][7][8]
Despite harvesting, biomass crops may sequester (trap) carbon. So for example soil organic carbon has been observed to be greater in switchgrass stands than in cultivated cropland soil, especially at depths below 12 inches.[9] The grass sequesters the carbon in its increased root biomass. But the perennial grass may need to be allowed to grow for several years before increases are measurable.[10]
# Biomass production for human use and consumption
This is a list of estimated biomass for human use and consumption. It does not include biomass which is not harvested or utilised.
Source: Whittaker, R. H. (1975). "The Biosphere and Man". In Leith, H. & Whittaker, R. H. Primary Productivity of the Biosphere. Springer-Verlag. pp. 305–328. ISBN 0-3870-7083-4. Unknown parameter |coauthors= ignored (help)CS1 maint: Multiple names: editors list (link) .mw-parser-output cite.citation{font-style:inherit}.mw-parser-output q{quotes:"\"""\"""'""'"}.mw-parser-output code.cs1-code{color:inherit;background:inherit;border:inherit;padding:inherit}.mw-parser-output .cs1-lock-free a{background:url("https://upload.wikimedia.org/wikipedia/commons/thumb/6/65/Lock-green.svg/9px-Lock-green.svg.png")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-limited a,.mw-parser-output .cs1-lock-registration a{background:url("https://upload.wikimedia.org/wikipedia/commons/thumb/d/d6/Lock-gray-alt-2.svg/9px-Lock-gray-alt-2.svg.png")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-subscription a{background:url("https://upload.wikimedia.org/wikipedia/commons/thumb/a/aa/Lock-red-alt-2.svg/9px-Lock-red-alt-2.svg.png")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration{color:#555}.mw-parser-output .cs1-subscription span,.mw-parser-output .cs1-registration span{border-bottom:1px dotted;cursor:help}.mw-parser-output .cs1-hidden-error{display:none;font-size:100%}.mw-parser-output .cs1-visible-error{display:none;font-size:100%}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration,.mw-parser-output .cs1-format{font-size:95%}.mw-parser-output .cs1-kern-left,.mw-parser-output .cs1-kern-wl-left{padding-left:0.2em}.mw-parser-output .cs1-kern-right,.mw-parser-output .cs1-kern-wl-right{padding-right:0.2em}; Ecological Studies Vol 14 (Berlin)
Darci and Taylre are biomass specialists. | https://www.wikidoc.org/index.php/Biomass | |
db2edd38930fc44815d5a99746dca17eafee21b7 | wikidoc | Bionade | Bionade
Bionade is a trademark of Bionade GmbH for an organic fermented and carbonated beverage, which is made in Germany. It is manufactured in a Bavarian town Ostheim vor der Rhön at the former beer brewery owned by Dieter Leipold - the creator of this drink.
"One of the goals was to make a drink for children that didn't have any artificial additives and that followed the purity requirements traditionally used to make beer." That meant a product with natural ingredients only: malt, water, sugar, fruit essences. No corn syrup, nothing artificial. And he'd use the same fermentation process he used to make beer — the trick would be leaving out the alcohol.
It took Leipold eight years and all €1.5 million of the family's money to perfect the recipe. Leipold found a way to ferment a nonalcoholic drink by converting the sugar that normally becomes alcohol into nonalcoholic gluconic acid. And because the acid strengthened the taste of sugar, Leipold only needed a fraction of the sugar found in a normal soft drink. Then came the flavors — elderberry, lychee, orange-ginger and herb — plus a spritz of carbonation.
Since its creation in 1995 it became popular in Germany as an alcohol-free organic soda, which is similar to lemonade in taste, but is prepared by fermenting malt, similar to beer. The fermentation process is followed by filtering, carbonation, addition of natural flavors and fortification with calcium and magnesium.
Bionade is available in 0,33 and rarely in 0,5 liter bottles. The main four available sorts are Holunder (Elderberry), Litschi (Lychee), Kräuter (Herbs), Ingwer-Orange (Ginger & Orange), and a new fifth variety is Forte.
73 millions bottles were sold in 2006. Bionade is already present in Austria, Switzerland, Scandinavia, the Benelux countries, Italy, Spain and Portugal, and is going to be present in Ireland, and one day also in the USA. | Bionade
Bionade is a trademark of Bionade GmbH for an organic fermented and carbonated beverage, which is made in Germany. It is manufactured in a Bavarian town Ostheim vor der Rhön at the former beer brewery owned by Dieter Leipold - the creator of this drink.
"One of the goals was to make a drink for children that didn't have any artificial additives and that followed the purity requirements traditionally used to make beer." That meant a product with natural ingredients only: malt, water, sugar, fruit essences. No corn syrup, nothing artificial. And he'd use the same fermentation process he used to make beer — the trick would be leaving out the alcohol.
It took Leipold eight years and all €1.5 million of the family's money to perfect the recipe. Leipold found a way to ferment a nonalcoholic drink by converting the sugar that normally becomes alcohol into nonalcoholic gluconic acid. And because the acid strengthened the taste of sugar, Leipold only needed a fraction of the sugar found in a normal soft drink. Then came the flavors — elderberry, lychee, orange-ginger and herb — plus a spritz of carbonation.[1]
Since its creation in 1995 it became popular in Germany as an alcohol-free organic soda, which is similar to lemonade in taste, but is prepared by fermenting malt, similar to beer. The fermentation process is followed by filtering, carbonation, addition of natural flavors and fortification with calcium and magnesium.
Bionade is available in 0,33 and rarely in 0,5 liter bottles. The main four available sorts are Holunder (Elderberry), Litschi (Lychee), Kräuter (Herbs), Ingwer-Orange (Ginger & Orange), and a new fifth variety is Forte.
73 millions bottles were sold in 2006.[2] Bionade is already present in Austria, Switzerland, Scandinavia, the Benelux countries, Italy, Spain and Portugal, and is going to be present in Ireland, and one day also in the USA.[3] | https://www.wikidoc.org/index.php/Bionade | |
22a79827087ffae54dce0cbd0417f9a841e51408 | wikidoc | Sulfate | Sulfate
# Overview
In inorganic chemistry, a sulfate (IUPAC-recommended spelling; also sulphate in British English) is a salt of sulfuric acid.
# Chemical properties
The sulfate ion is a polyatomic anion with the empirical formula SO42− and a molecular mass of 96.06 daltons; it consists of a central sulfur atom surrounded by four equivalent oxygen atoms in a tetrahedral arrangement. The sulfate ion carries a negative two charge and is the conjugate base of the bisulfate (or hydrogen sulfate) ion, HSO4−, which is the conjugate base of H2SO4, sulfuric acid. Organic sulfates, such as dimethyl sulfate, are covalent compounds and esters of sulfuric acid.
## Preparation
Methods of preparing ionic sulfates include:
- dissolving a metal in sulfuric acid
- reacting sulfuric acid with a metal hydroxide or oxide
- oxidizing metal sulfides or sulfites
## Properties
Many examples of ionic sulfates are known, and many of these are highly soluble in water. Exceptions include calcium sulfate, strontium sulfate, and barium sulfate, which are poorly soluble. The barium derivative is useful in the gravimetric analysis of sulfate: one adds a solution of, perhaps, barium chloride to a solution containing sulfate ions. The appearance of a white precipitate, which is barium sulfate, indicates that sulfate anions are present.
The sulfate ion can act as a ligand attaching either by one oxygen (monodentate) or by two oxygens as either a chelate or a bridge. An example is the neutral metal complex PtSO4P(C6H5)32 where the sulfate ion is acting as a bidentate ligand. The metal-oxygen bonds in sulfate complexes can have significant covalent character.
## Structure and bonding
The S-O bond length of 149 pm is shorter than expected for a S-O single bond; for example the bond lengths in sulfuric acid are 157 pm for S-OH. The tetrahedral geometry of the sulfate ion is as predicted by VSEPR theory.
The first description of the bonding in modern terms was by Gilbert Lewis in his groundbreaking paper of 1916 where he described the bonding in terms of electron octets around each atom, i.e. no double bonds and a formal charge of 2+ on the sulfur atom.
Later, Linus Pauling used valence bond theory to propose that the most significant resonance canonicals had two π bonds (see above) involving d orbitals. His reasoning was that the charge on sulfur was thus reduced, in accordance with his principle of electroneutrality. The double bonding was taken by Pauling to account for the shortness of the S-O bond (149 pm).
Pauling's use of d orbitals provoked a debate on the relative importance of π bonding and bond polarity (electrostatic attraction) in causing the shortening of the S-O bond. The outcome was a broad consensus that d orbitals play a role, but are not as significant as Pauling had believed. A widely accepted description involves pπ - dπ bonding, initially proposed by D.W.J Cruickshank, where fully occupied p orbitals on oxygen overlap with empty sulfur d orbitals (principally the dz2 and dx2-y2). In this description, while there is some π character to the S-O bonds, the bond has significant ionic character. This explanation is quoted in some current textbooks. The Pauling bonding representation for sulfate and other main group compounds with oxygen is a common way of representing the bonding in many textbooks.
# Uses
Sulfates are important in both the chemical industry and biological systems:
- The lead-acid battery typically uses sulfuric acid.
- Some anaerobic microorganisms, such as those living near deep sea thermal vents use sulfates as electron acceptors.
- Copper sulfate is a common algaecide.
- Magnesium sulfate, commonly known as Epsom salts, is used in therapeutic baths.
- Gypsum, the natural mineral form of hydrated calcium sulfate, is used to produce plaster.
- The sulfate ion is used as counter ion for some cationic drugs.
# History
Some sulfates were known to alchemists. The vitriol salts, from the latin vitreolum, glassy, were so-called because they were some of the first transparent crystals known. Green vitriol is ferrous sulfate heptahydrate, FeSO4·7H2O; blue vitriol is copper sulfate pentahydrate, CuSO4·5H2O and white vitriol is zinc sulfate heptahydrate, ZnSO4·7H2O. Alum, a double sulfate with the formula K2Al2(SO4)4·24H2O, figured in the development of the chemical industry.
# Environmental effects
Sulfates occur as microscopic particles (aerosols) resulting from fossil fuel and biomass combustion. They increase the acidity of the atmosphere and form acid rain.
## Main effects on climate
The main direct effect of sulfates on the climate involves the scattering of light, effectively increasing the Earth's albedo. This effect is moderately well understood and leads to a cooling from the negative radiative forcing of about 0.5 W/m2 relative to pre-industrial values, partially offsetting the larger (about 2.4 W/m2) warming effect of greenhouse gases. The effect is strongly spatially non-uniform, being largest downstream of large industrial areas.
The first indirect effect is also known as the Twomey effect. Sulfate aerosols can act as cloud condensation nuclei and this leads to greater numbers of smaller droplets of water. Lots of smaller droplets can diffuse light more efficiently than just a few larger droplets.
The second indirect effect is the further knock-on effects of having more cloud condensation nuclei. It is proposed that these include the suppression of drizzle, increased cloud height, to facilitate cloud formation at low humidities and longer cloud lifetime. Sulfate may also result in changes in the particle size distribution, which can affect the clouds radiative properties in ways that are not fully understood. Chemical effects such as the dissolution of soluble gases and slightly soluble substances, surface tension depression by organic substances and accommodation coefficient changes are also included in the second indirect effect.
The indirect effects probably have a cooling effect, perhaps up to 2 W/m2, although the uncertainty is very large. Sulfates are therefore implicated in global dimming, which may have acted to offset some of the effects of global warming.
# Other sulfur oxoanions | Sulfate
Template:Chembox/Top
Template:Chembox/SectGeneral
Template:Chembox/Formula
Template:Chembox/MolarMass
Template:Chembox/CASNo
Template:Chembox/SectStructure
Template:Chembox/MolecularShape
Template:Chembox/SectRelated
Template:Chembox/RelatedCpds
Template:Chembox/Bottom
# Overview
In inorganic chemistry, a sulfate (IUPAC-recommended spelling; also sulphate in British English) is a salt of sulfuric acid.
# Chemical properties
The sulfate ion is a polyatomic anion with the empirical formula SO42− and a molecular mass of 96.06 daltons; it consists of a central sulfur atom surrounded by four equivalent oxygen atoms in a tetrahedral arrangement. The sulfate ion carries a negative two charge and is the conjugate base of the bisulfate (or hydrogen sulfate) ion, HSO4−, which is the conjugate base of H2SO4, sulfuric acid. Organic sulfates, such as dimethyl sulfate, are covalent compounds and esters of sulfuric acid.
## Preparation
Methods of preparing ionic sulfates include:[1]
- dissolving a metal in sulfuric acid
- reacting sulfuric acid with a metal hydroxide or oxide
- oxidizing metal sulfides or sulfites
## Properties
Many examples of ionic sulfates are known, and many of these are highly soluble in water. Exceptions include calcium sulfate, strontium sulfate, and barium sulfate, which are poorly soluble. The barium derivative is useful in the gravimetric analysis of sulfate: one adds a solution of, perhaps, barium chloride to a solution containing sulfate ions. The appearance of a white precipitate, which is barium sulfate, indicates that sulfate anions are present.
The sulfate ion can act as a ligand attaching either by one oxygen (monodentate) or by two oxygens as either a chelate or a bridge.[1] An example is the neutral metal complex PtSO4P(C6H5)32 where the sulfate ion is acting as a bidentate ligand. The metal-oxygen bonds in sulfate complexes can have significant covalent character.
## Structure and bonding
The S-O bond length of 149 pm is shorter than expected for a S-O single bond; for example the bond lengths in sulfuric acid are 157 pm for S-OH. The tetrahedral geometry of the sulfate ion is as predicted by VSEPR theory.
The first description of the bonding in modern terms was by Gilbert Lewis in his groundbreaking paper of 1916 where he described the bonding in terms of electron octets around each atom, i.e. no double bonds and a formal charge of 2+ on the sulfur atom.[2]
Later, Linus Pauling used valence bond theory to propose that the most significant resonance canonicals had two π bonds (see above) involving d orbitals. His reasoning was that the charge on sulfur was thus reduced, in accordance with his principle of electroneutrality.[3] The double bonding was taken by Pauling to account for the shortness of the S-O bond (149 pm).
Pauling's use of d orbitals provoked a debate on the relative importance of π bonding and bond polarity (electrostatic attraction) in causing the shortening of the S-O bond. The outcome was a broad consensus that d orbitals play a role, but are not as significant as Pauling had believed.[4][5] A widely accepted description involves pπ - dπ bonding, initially proposed by D.W.J Cruickshank, where fully occupied p orbitals on oxygen overlap with empty sulfur d orbitals (principally the dz2 and dx2-y2).[6] In this description, while there is some π character to the S-O bonds, the bond has significant ionic character. This explanation is quoted in some current textbooks.[7][1] The Pauling bonding representation for sulfate and other main group compounds with oxygen is a common way of representing the bonding in many textbooks.[7][1]
# Uses
Sulfates are important in both the chemical industry and biological systems:
- The lead-acid battery typically uses sulfuric acid.
- Some anaerobic microorganisms, such as those living near deep sea thermal vents use sulfates as electron acceptors.
- Copper sulfate is a common algaecide.
- Magnesium sulfate, commonly known as Epsom salts, is used in therapeutic baths.
- Gypsum, the natural mineral form of hydrated calcium sulfate, is used to produce plaster.
- The sulfate ion is used as counter ion for some cationic drugs.
# History
Some sulfates were known to alchemists. The vitriol salts, from the latin vitreolum, glassy, were so-called because they were some of the first transparent crystals known.[8] Green vitriol is ferrous sulfate heptahydrate, FeSO4·7H2O; blue vitriol is copper sulfate pentahydrate, CuSO4·5H2O and white vitriol is zinc sulfate heptahydrate, ZnSO4·7H2O. Alum, a double sulfate with the formula K2Al2(SO4)4·24H2O, figured in the development of the chemical industry.
# Environmental effects
Sulfates occur as microscopic particles (aerosols) resulting from fossil fuel and biomass combustion. They increase the acidity of the atmosphere and form acid rain.
## Main effects on climate
The main direct effect of sulfates on the climate involves the scattering of light, effectively increasing the Earth's albedo. This effect is moderately well understood and leads to a cooling from the negative radiative forcing of about 0.5 W/m2 relative to pre-industrial values,[9] partially offsetting the larger (about 2.4 W/m2) warming effect of greenhouse gases. The effect is strongly spatially non-uniform, being largest downstream of large industrial areas.
The first indirect effect is also known as the Twomey effect. Sulfate aerosols can act as cloud condensation nuclei and this leads to greater numbers of smaller droplets of water. Lots of smaller droplets can diffuse light more efficiently than just a few larger droplets.
The second indirect effect is the further knock-on effects of having more cloud condensation nuclei. It is proposed that these include the suppression of drizzle, increased cloud height, [10] to facilitate cloud formation at low humidities and longer cloud lifetime.[11] Sulfate may also result in changes in the particle size distribution, which can affect the clouds radiative properties in ways that are not fully understood. Chemical effects such as the dissolution of soluble gases and slightly soluble substances, surface tension depression by organic substances and accommodation coefficient changes are also included in the second indirect effect.[12]
The indirect effects probably have a cooling effect, perhaps up to 2 W/m2, although the uncertainty is very large. Sulfates are therefore implicated in global dimming, which may have acted to offset some of the effects of global warming.
# Other sulfur oxoanions | https://www.wikidoc.org/index.php/Bisulfate | |
92aab88443f538d470d492dfbe4da6619bdc1f4f | wikidoc | Blister | Blister
# Overview
A blister is a small pocket of fluid within the upper layers of the skin. Blisters can be filled with blood (known as blood blisters) or with pus (if they become infected). However, most blisters are filled with a clear fluid called serum. Serum is the part of the blood that remains after red blood cells and clotting agents have been removed.
A blister usually forms because the outer layer of the skin has become damaged. Fluid collects under the damaged layer of skin, cushioning the tissue underneath, protecting it from further damage and allowing it to heal.
A blood-blister usually forms when a small blood vessel close to the surface of the skin ruptures (breaks) and blood leaks into a tear between the layers of skin. This can happen if the skin is crushed, pinched or squeezed very tightly.
Blisters can also form as the result of certain medical conditions.
# Causes
Blisters are usually caused by injury to the skin from heat (for example from sunburn or a scald) or from friction.
Friction or heat on the skin can create a tear between the upper layer of the skin (the epidermis) and the layers beneath. When this happens the surface of the skin remains intact, but is pushed outwards as serum seeps into the newly created space between the layers.
Any rubbing of the skin can cause a blister if it is continued for long enough. Short periods of intense rubbing can also cause a blister. Blisters are most common on the hands and feet, as these parts of your body may rub against shoes or handheld equipment. Blisters form more easily on moist skin than on dry or soaked skin, and are more common in warm conditions.
Sometimes, the skin can blister when it comes into contact with a cosmetic, detergent, solvent or other chemical. This is known as contact dermatitis. Blisters can also develop as a result of an allergic reaction to an insect bite or sting.
There are a number of medical conditions that cause blisters. The most common are:
- chickenpox,
- herpes,
- impetigo, and,
- a form of eczema called pompholyx.
Other, much rarer conditions that cause blisters include:
- Bullous pemphigoid - a skin disease that causes large, tightly-filled blisters to develop. The disease usually affects people over the age of 60.
- Pemphigus - a serious skin disease in which blisters develop if pressure is applied to the skin. The blisters burst easily, leaving raw areas that can become infected.
- Dermatitis herpetiformis - a skin disease that causes intensely itchy blisters, usually on the elbows, knees, back and buttocks. The blisters usually develop in patches of the same shape and size on both sides of the body.
- Chronic bullous dermatosis of childhood - a disease that causes clusters of blisters on the face, mouth or genitals.
## Causes by Organ System
## Causes in Alphabetical Order
# Prevention
You can prevent blisters on your feet by wearing comfortable, well-fitting shoes and clean socks that you change daily. Blisters are more likely to develop on skin that is moist, so if you have particularly sweaty feet you may find wearing moisture-absorbing socks or changing your socks twice a day, necessary to prevent blisters. If you are exercising or playing sport, special sports socks can help keep your feet drier and reduce the chance of a blister.
Before going for a long walk, make sure that the shoes you are planning to wear have been broken in. If you do become aware of a hot area on your foot when walking, exercising or playing sport, stop immediately and tape some padding over the area.
To avoid blisters on your hands, wear work gloves when using tools such as a shovel or pickaxe, and when doing manual work such as gardening. You should also wear gloves when handling detergents, cleaning products, solvents and other chemicals.
To avoid friction to make a tear between the upper skin layer and the layers beneath one has to prevent friction forces being transmitted to the upper skin. This can be attained with a lubricant, typically talcum powder. Wearing gloves with talcum powder inside makes hands almost immune to blisters. The same goes for feet in shoes with talcum powder inside.
You should use sunscreen and cover up during the hottest part of the day to avoid blisters from sunburn. Moisturising, after-sun or calamine lotions can help to ease the discomfort if you do get burnt.
# Treatment
Most blisters heal naturally and do not require medical attention. As new skin grows beneath the blister, the fluid contained within it will be slowly reabsorbed by your body and the skin on top will dry and peel off.
The unbroken skin over a blister provides a natural barrier to infection. This means that you should try to keep blisters intact and unbroken in order to avoid infection. Try not to pierce a blister with a needle, but allow it to break on its own once the skin underneath has healed. If the blister is in a place (such as a hand or foot) that makes it extra painful, follow these steps:
1. Wash your hands and the blister with soap and water, and stearalize the blister with rubbing alcohol.
2. Steralize a pin with rubbing alcohol.
3. Make small pinpricks on the edge of the blister and drain the fluid through these.
4. Cover the blister with first-aid ointment and a sterile bandage.
Cover small blisters with a plaster (adhesive dressing). Larger blisters should be covered with a gauze pad or dressing that you can then tape in place. If you have a blister in a position that is causing you pain or that makes it likely to burst (such as on the sole of your foot), its important to cover it with a soft dressing to pad and protect it. Then change the dressing daily.
If a blister bursts, don't peel off the dead skin on top of the blister. Gently press the area to get rid of all the fluid inside, and then cover the blister and the area around it with a dry, sterile dressing to protect it from infection until it heals.
Blood blisters should also be left to heal naturally. As with other blisters, if a blood blister bursts it is important to keep the area clean and dry, and protect it with a sterile dressing to prevent infection.
Blood blisters are often painful, and you may wish to apply an ice pack to the area immediately after the injury that caused it. You should apply the ice pack for between 10 and 30 minutes. The ice should not touch your skin directly as this may cause a cold burn, so place a towel over the injured part first.
Even when popped as described above, a blister can become infected, Staph aureus infections being most common. Blisters that have become infected can be treated with antibiotics prescribed by your GP. Blisters caused by a medical condition are treated by treating the underlying condition.
# Related Chapters
- Dracunculiasis
- Herpangina
- Herpes zoster
- Ulcer | Blister
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
# Overview
A blister is a small pocket of fluid within the upper layers of the skin. Blisters can be filled with blood (known as blood blisters) or with pus (if they become infected). However, most blisters are filled with a clear fluid called serum. Serum is the part of the blood that remains after red blood cells and clotting agents have been removed.
A blister usually forms because the outer layer of the skin has become damaged. Fluid collects under the damaged layer of skin, cushioning the tissue underneath, protecting it from further damage and allowing it to heal.
A blood-blister usually forms when a small blood vessel close to the surface of the skin ruptures (breaks) and blood leaks into a tear between the layers of skin. This can happen if the skin is crushed, pinched or squeezed very tightly.
Blisters can also form as the result of certain medical conditions.
# Causes
Blisters are usually caused by injury to the skin from heat (for example from sunburn or a scald) or from friction.
Friction or heat on the skin can create a tear between the upper layer of the skin (the epidermis) and the layers beneath. When this happens the surface of the skin remains intact, but is pushed outwards as serum seeps into the newly created space between the layers.
Any rubbing of the skin can cause a blister if it is continued for long enough. Short periods of intense rubbing can also cause a blister. Blisters are most common on the hands and feet, as these parts of your body may rub against shoes or handheld equipment. Blisters form more easily on moist skin than on dry or soaked skin, and are more common in warm conditions.
Sometimes, the skin can blister when it comes into contact with a cosmetic, detergent, solvent or other chemical. This is known as contact dermatitis. Blisters can also develop as a result of an allergic reaction to an insect bite or sting.
There are a number of medical conditions that cause blisters. The most common are:
- chickenpox,
- herpes,
- impetigo, and,
- a form of eczema called pompholyx.
Other, much rarer conditions that cause blisters include:
- Bullous pemphigoid - a skin disease that causes large, tightly-filled blisters to develop. The disease usually affects people over the age of 60.
- Pemphigus - a serious skin disease in which blisters develop if pressure is applied to the skin. The blisters burst easily, leaving raw areas that can become infected.
- Dermatitis herpetiformis - a skin disease that causes intensely itchy blisters, usually on the elbows, knees, back and buttocks. The blisters usually develop in patches of the same shape and size on both sides of the body.
- Chronic bullous dermatosis of childhood - a disease that causes clusters of blisters on the face, mouth or genitals.
## Causes by Organ System
## Causes in Alphabetical Order
# Prevention
You can prevent blisters on your feet by wearing comfortable, well-fitting shoes and clean socks that you change daily. Blisters are more likely to develop on skin that is moist, so if you have particularly sweaty feet you may find wearing moisture-absorbing socks or changing your socks twice a day, necessary to prevent blisters. If you are exercising or playing sport, special sports socks can help keep your feet drier and reduce the chance of a blister.
Before going for a long walk, make sure that the shoes you are planning to wear have been broken in. If you do become aware of a hot area on your foot when walking, exercising or playing sport, stop immediately and tape some padding over the area.
To avoid blisters on your hands, wear work gloves when using tools such as a shovel or pickaxe, and when doing manual work such as gardening. You should also wear gloves when handling detergents, cleaning products, solvents and other chemicals.
To avoid friction to make a tear between the upper skin layer and the layers beneath one has to prevent friction forces being transmitted to the upper skin. This can be attained with a lubricant, typically talcum powder. Wearing gloves with talcum powder inside makes hands almost immune to blisters. The same goes for feet in shoes with talcum powder inside.
You should use sunscreen and cover up during the hottest part of the day to avoid blisters from sunburn. Moisturising, after-sun or calamine lotions can help to ease the discomfort if you do get burnt.
# Treatment
Most blisters heal naturally and do not require medical attention. As new skin grows beneath the blister, the fluid contained within it will be slowly reabsorbed by your body and the skin on top will dry and peel off.
The unbroken skin over a blister provides a natural barrier to infection. This means that you should try to keep blisters intact and unbroken in order to avoid infection. Try not to pierce a blister with a needle, but allow it to break on its own once the skin underneath has healed. If the blister is in a place (such as a hand or foot) that makes it extra painful, follow these steps:
1. Wash your hands and the blister with soap and water, and stearalize the blister with rubbing alcohol.
2. Steralize a pin with rubbing alcohol.
3. Make small pinpricks on the edge of the blister and drain the fluid through these.
4. Cover the blister with first-aid ointment and a sterile bandage.[1]
Cover small blisters with a plaster (adhesive dressing). Larger blisters should be covered with a gauze pad or dressing that you can then tape in place. If you have a blister in a position that is causing you pain or that makes it likely to burst (such as on the sole of your foot), its important to cover it with a soft dressing to pad and protect it. Then change the dressing daily.
If a blister bursts, don't peel off the dead skin on top of the blister. Gently press the area to get rid of all the fluid inside, and then cover the blister and the area around it with a dry, sterile dressing to protect it from infection until it heals.
Blood blisters should also be left to heal naturally. As with other blisters, if a blood blister bursts it is important to keep the area clean and dry, and protect it with a sterile dressing to prevent infection.
Blood blisters are often painful, and you may wish to apply an ice pack to the area immediately after the injury that caused it. You should apply the ice pack for between 10 and 30 minutes. The ice should not touch your skin directly as this may cause a cold burn, so place a towel over the injured part first.
Even when popped as described above, a blister can become infected, Staph aureus infections being most common. Blisters that have become infected can be treated with antibiotics prescribed by your GP. Blisters caused by a medical condition are treated by treating the underlying condition.
# Related Chapters
- Dracunculiasis
- Herpangina
- Herpes zoster
- Ulcer | https://www.wikidoc.org/index.php/Blister | |
63db725cd12d55e5b8780187743f6f3a467c08c7 | wikidoc | Red eye | Red eye
For resident survival guide, click here
Synonyms and keywords: Bloodshot eye
# Overview
Red eye is one of the most common complaints managed by primary care physicians though in some cases it heralds a serious and life-threatening condition needing urgent referral to ophthalmologist. The etiology of red eye can be infectious, traumatic, inflammatory, allergic, autoimmune and rarely secondary to tumors. Red eye stems from pathologies of eye lid, conjunctiva, cornea, sclera and uvea. Signs and/or symptoms such as photophobia, pain, visual acuity, itchiness, foreign body sensation and if the condition is unilateral or bilateral, must be documented. Whenever a red flag is identified in a patient presenting with red eye, the clinician must refer the patient for a same-day ophthalmologist consult.
# Classification
There is no established system for the classification of red eye.
# Causes
- The cause of red eye is diagnosed through a comprehensive eye examination and patient's history. The most common cause of red eye is conjunctivitis and the most common etiology is viral. There are other causes though, and differential diagnosis must include other diseases such as corneal abrasion, blepharitis, subconjunctival hemorrhage, foreign body, iritis, keratitis, chemical burn, glaucoma, and scleritis that may confound the physician.
- Conjunctivitis, episcleritis and subconjunctival haemorrhage make up about 70% of the primary care red eye consultations.
## Sight-threatening causes
The most common causes of sight-threatening causes of red eye include
- Keratitis
- Scleritis
- Acute glaucoma
- Orbital cellulitis
- Foreign body trauma
- Chemical burns
# Differentiating Red eye from other Diseases
While evaluating patients presenting with red eye, a crucial step is to identify the patients that have sight-threatening causes. This can be evaluated by asking historical questions about associated symptoms and performing a complete ocular examination. Associated symptoms include:
- Pain
- Photophobia
- Visual acuity
- History of trauma or exposure
- History of secretion
- History of systemic symptoms
# Treatment
In patients presenting with red eye, it is important to take a full detailed history and physical examination. In assessment of patient's red eye, the diagnosis can be narrowed by distinguishing other associated symptoms.
For more information on treatment click here.
# Related Chapters
- List of eye diseases and disorders
- ↑ Jump up to: 1.0 1.1 Tarff, Andreina; Behrens, Ashley (2017). "Ocular Emergencies". Medical Clinics of North America. 101 (3): 615–639. doi:10.1016/j.mcna.2016.12.013. ISSN 0025-7125..mw-parser-output cite.citation{font-style:inherit}.mw-parser-output q{quotes:"\"""\"""'""'"}.mw-parser-output code.cs1-code{color:inherit;background:inherit;border:inherit;padding:inherit}.mw-parser-output .cs1-lock-free a{background:url("")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-limited a,.mw-parser-output .cs1-lock-registration a{background:url("")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-subscription a{background:url("")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration{color:#555}.mw-parser-output .cs1-subscription span,.mw-parser-output .cs1-registration span{border-bottom:1px dotted;cursor:help}.mw-parser-output .cs1-hidden-error{display:none;font-size:100%}.mw-parser-output .cs1-visible-error{display:none;font-size:100%}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration,.mw-parser-output .cs1-format{font-size:95%}.mw-parser-output .cs1-kern-left,.mw-parser-output .cs1-kern-wl-left{padding-left:0.2em}.mw-parser-output .cs1-kern-right,.mw-parser-output .cs1-kern-wl-right{padding-right:0.2em}
- ↑ Cronau H, Kankanala RR, Mauger T (January 2010). "Diagnosis and management of red eye in primary care" (2): 137–44.
- ↑ Kilduff C, Lois C (2016). "Red eyes and red-flags: improving ophthalmic assessment and referral in primary care". BMJ Qual Improv Rep. 5 (1). doi:10.1136/bmjquality.u211608.w4680. PMC 4964165. PMID 27493748.
- ↑ Narayana, Sirisha; McGee, Steven (2015). "Bedside Diagnosis of the 'Red Eye': A Systematic Review". The American Journal of Medicine. 128 (11): 1220–1224.e1. doi:10.1016/j.amjmed.2015.06.026. ISSN 0002-9343.
- ↑ Sethuraman U, Kamat D (2009). "The red eye: evaluation and management". Clin Pediatr (Phila). 48 (6): 588–600. doi:10.1177/0009922809333094. PMID 19357422.
- ↑ Gilani CJ, Yang A, Yonkers M, Boysen-Osborn M (2017). "Differentiating Urgent and Emergent Causes of Acute Red Eye for the Emergency Physician". West J Emerg Med. 18 (3): 509–517. doi:10.5811/westjem.2016.12.31798. PMC 5391903. PMID 28435504.CS1 maint: Multiple names: authors list (link)
- ↑ Jump up to: 7.0 7.1 7.2 Azari AA, Barney NP (2013). "Conjunctivitis: a systematic review of diagnosis and treatment". JAMA. 310 (16): 1721–9. doi:10.1001/jama.2013.280318. PMC 4049531. PMID 24150468.
- ↑ Putnam CM (2016). "Diagnosis and management of blepharitis: an optometrist's perspective". Clin Optom (Auckl). 8: 71–78. doi:10.2147/OPTO.S84795. PMC 6095371. PMID 30214351.
- ↑ Tarlan B, Kiratli H (2013). "Subconjunctival hemorrhage: risk factors and potential indicators". Clin Ophthalmol. 7: 1163–70. doi:10.2147/OPTH.S35062. PMC 3702240. PMID 23843690.
- ↑ Weinreb RN, Aung T, Medeiros FA (2014). "The pathophysiology and treatment of glaucoma: a review". JAMA. 311 (18): 1901–11. doi:10.1001/jama.2014.3192. PMC 4523637. PMID 24825645.CS1 maint: Multiple names: authors list (link)
- ↑ Galor A, Thorne JE (2007). "Scleritis and peripheral ulcerative keratitis". Rheum Dis Clin North Am. 33 (4): 835–54, vii. doi:10.1016/j.rdc.2007.08.002. PMC 2212596. PMID 18037120. | Red eye
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Seyed Arash Javadmoosavi, MD[2]
For patient information, click here
For resident survival guide, click here
Synonyms and keywords: Bloodshot eye
# Overview
Red eye is one of the most common complaints managed by primary care physicians though in some cases it heralds a serious and life-threatening condition needing urgent referral to ophthalmologist. The etiology of red eye can be infectious, traumatic, inflammatory, allergic, autoimmune and rarely secondary to tumors. Red eye stems from pathologies of eye lid, conjunctiva, cornea, sclera and uvea. Signs and/or symptoms such as photophobia, pain, visual acuity, itchiness, foreign body sensation and if the condition is unilateral or bilateral, must be documented. Whenever a red flag is identified in a patient presenting with red eye, the clinician must refer the patient for a same-day ophthalmologist consult.
# Classification
There is no established system for the classification of red eye.
# Causes
- The cause of red eye is diagnosed through a comprehensive eye examination and patient's history. The most common cause of red eye is conjunctivitis and the most common etiology is viral. There are other causes though, and differential diagnosis must include other diseases such as corneal abrasion, blepharitis, subconjunctival hemorrhage, foreign body, iritis, keratitis, chemical burn, glaucoma, and scleritis that may confound the physician.[1][2]
- Conjunctivitis, episcleritis and subconjunctival haemorrhage make up about 70% of the primary care red eye consultations.
## Sight-threatening causes
The most common causes of sight-threatening causes of red eye include[3]
- Keratitis
- Scleritis
- Acute glaucoma
- Orbital cellulitis
- Foreign body trauma
- Chemical burns
# Differentiating Red eye from other Diseases
While evaluating patients presenting with red eye, a crucial step is to identify the patients that have sight-threatening causes. This can be evaluated by asking historical questions about associated symptoms and performing a complete ocular examination. Associated symptoms include:[4][5]
- Pain
- Photophobia
- Visual acuity
- History of trauma or exposure
- History of secretion
- History of systemic symptoms
# Treatment
In patients presenting with red eye, it is important to take a full detailed history and physical examination. In assessment of patient's red eye, the diagnosis can be narrowed by distinguishing other associated symptoms.
For more information on treatment click here.
# Related Chapters
- List of eye diseases and disorders
Template:WH
Template:WS
- ↑ Jump up to: 1.0 1.1 Tarff, Andreina; Behrens, Ashley (2017). "Ocular Emergencies". Medical Clinics of North America. 101 (3): 615–639. doi:10.1016/j.mcna.2016.12.013. ISSN 0025-7125..mw-parser-output cite.citation{font-style:inherit}.mw-parser-output q{quotes:"\"""\"""'""'"}.mw-parser-output code.cs1-code{color:inherit;background:inherit;border:inherit;padding:inherit}.mw-parser-output .cs1-lock-free a{background:url("https://upload.wikimedia.org/wikipedia/commons/thumb/6/65/Lock-green.svg/9px-Lock-green.svg.png")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-limited a,.mw-parser-output .cs1-lock-registration a{background:url("https://upload.wikimedia.org/wikipedia/commons/thumb/d/d6/Lock-gray-alt-2.svg/9px-Lock-gray-alt-2.svg.png")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-subscription a{background:url("https://upload.wikimedia.org/wikipedia/commons/thumb/a/aa/Lock-red-alt-2.svg/9px-Lock-red-alt-2.svg.png")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration{color:#555}.mw-parser-output .cs1-subscription span,.mw-parser-output .cs1-registration span{border-bottom:1px dotted;cursor:help}.mw-parser-output .cs1-hidden-error{display:none;font-size:100%}.mw-parser-output .cs1-visible-error{display:none;font-size:100%}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration,.mw-parser-output .cs1-format{font-size:95%}.mw-parser-output .cs1-kern-left,.mw-parser-output .cs1-kern-wl-left{padding-left:0.2em}.mw-parser-output .cs1-kern-right,.mw-parser-output .cs1-kern-wl-right{padding-right:0.2em}
- ↑ Cronau H, Kankanala RR, Mauger T (January 2010). "Diagnosis and management of red eye in primary care" (2): 137–44.
- ↑ Kilduff C, Lois C (2016). "Red eyes and red-flags: improving ophthalmic assessment and referral in primary care". BMJ Qual Improv Rep. 5 (1). doi:10.1136/bmjquality.u211608.w4680. PMC 4964165. PMID 27493748.
- ↑ Narayana, Sirisha; McGee, Steven (2015). "Bedside Diagnosis of the 'Red Eye': A Systematic Review". The American Journal of Medicine. 128 (11): 1220–1224.e1. doi:10.1016/j.amjmed.2015.06.026. ISSN 0002-9343.
- ↑ Sethuraman U, Kamat D (2009). "The red eye: evaluation and management". Clin Pediatr (Phila). 48 (6): 588–600. doi:10.1177/0009922809333094. PMID 19357422.
- ↑ Gilani CJ, Yang A, Yonkers M, Boysen-Osborn M (2017). "Differentiating Urgent and Emergent Causes of Acute Red Eye for the Emergency Physician". West J Emerg Med. 18 (3): 509–517. doi:10.5811/westjem.2016.12.31798. PMC 5391903. PMID 28435504.CS1 maint: Multiple names: authors list (link)
- ↑ Jump up to: 7.0 7.1 7.2 Azari AA, Barney NP (2013). "Conjunctivitis: a systematic review of diagnosis and treatment". JAMA. 310 (16): 1721–9. doi:10.1001/jama.2013.280318. PMC 4049531. PMID 24150468.
- ↑ Putnam CM (2016). "Diagnosis and management of blepharitis: an optometrist's perspective". Clin Optom (Auckl). 8: 71–78. doi:10.2147/OPTO.S84795. PMC 6095371. PMID 30214351.
- ↑ Tarlan B, Kiratli H (2013). "Subconjunctival hemorrhage: risk factors and potential indicators". Clin Ophthalmol. 7: 1163–70. doi:10.2147/OPTH.S35062. PMC 3702240. PMID 23843690.
- ↑ Weinreb RN, Aung T, Medeiros FA (2014). "The pathophysiology and treatment of glaucoma: a review". JAMA. 311 (18): 1901–11. doi:10.1001/jama.2014.3192. PMC 4523637. PMID 24825645.CS1 maint: Multiple names: authors list (link)
- ↑ Galor A, Thorne JE (2007). "Scleritis and peripheral ulcerative keratitis". Rheum Dis Clin North Am. 33 (4): 835–54, vii. doi:10.1016/j.rdc.2007.08.002. PMC 2212596. PMID 18037120. | https://www.wikidoc.org/index.php/Blood_shot_eye | |
dcdd5c2570eba5f4c97999f2d2552c1702c9ed7a | wikidoc | Blue 88 | Blue 88
A blue colored pill that was a mix of calming drugs, mainly barbiturates, used to treat American Soldiers in the Second World War who suffered from battle fatigue. In most cases it was used to induce sleep.
# Use during World War II
A Public Broadcasting Service piece called "Battle of the Bulge" from the American Experience series which was broadcast in 1994 provided an overview of the use of this pharmaceutical. This documentary, produced by Boston, Massachusett's WGBH Educational Foundation, reviewed the pivotal World War II German offensive in the Ardennes of France in 1944-1945. The following is a summary of the transcript that relates to this drug.
Because of increasing losses during the Ardennes Offensive, the Allied forces began to suffer from a shortage of soldiers. Those not severely wounded or suffering from battle fatigue were encouraged to return to the front lines. A 4th Medical Battalion Special Troops dental officer of the 4th Infantry Division, Captain Ben Kimmelman, was active in the medical corps and witnessed the effects of the battle:
One out of four soldiers wounded during the "Battle of the Bulge" were classified as "psychiatric casualties." Captain Kimmelman continues:
Capt. Kimmelman was later captured along with the rest of the 2-8 Infantry Regiment ("Easy Company") during the German campaign and survived the war. | Blue 88
A blue colored pill that was a mix of calming drugs, mainly barbiturates, used to treat American Soldiers in the Second World War who suffered from battle fatigue. In most cases it was used to induce sleep.
# Use during World War II
A Public Broadcasting Service piece called "Battle of the Bulge" from the American Experience series which was broadcast in 1994 provided an overview of the use of this pharmaceutical. This documentary, produced by Boston, Massachusett's WGBH Educational Foundation, reviewed the pivotal World War II German offensive in the Ardennes of France in 1944-1945. The following is a summary of the transcript that relates to this drug.
Because of increasing losses during the Ardennes Offensive, the Allied forces began to suffer from a shortage of soldiers. Those not severely wounded or suffering from battle fatigue were encouraged to return to the front lines. A 4th Medical Battalion Special Troops dental officer of the 4th Infantry Division, Captain Ben Kimmelman, was active in the medical corps and witnessed the effects of the battle:
One out of four soldiers wounded during the "Battle of the Bulge" were classified as "psychiatric casualties." Captain Kimmelman continues:
Capt. Kimmelman was later captured along with the rest of the 2-8 Infantry Regiment ("Easy Company") during the German campaign and survived the war. | https://www.wikidoc.org/index.php/Blue_88 | |
a111b5a96a3c3372cf290d72bc7d5b7b572dc297 | wikidoc | DNA end | DNA end
# Overview
DNA end or sticky end refers to the properties of the end of a molecule of DNA. The concept is important in molecular biology, especially in cloning or when subcloning insert DNA into vector DNA. All the terms can also be used in reference to RNA.
# Single-stranded DNA molecules
A single-stranded non-circular DNA molecule has two non-identical ends, the 3' end and the 5' end (usually pronounced "three prime end" and "five prime end". The numbers refer to the numbering of carbon atoms in the deoxyribose, which is a sugar forming an important part of the backbone of the DNA molecule. In the backbone of DNA the 5' carbon of one deoxyribose is linked to the 3' carbon of another by a phosphate group. The 5' carbon of this deoxyribose is again linked to the 3' carbon of the next, and so forth.
# Variations in double-stranded molecules
When a molecule of DNA is double stranded, as DNA usually is, the two strands run in opposite directions. Therefore, one end of the molecule will have the 3' end of strand 1 and the 5' end of strand 2, and vice versa in the other end. However, the fact that the molecule is two stranded allows numerous different variations.
## Blunt ends
The simplest DNA end of a double stranded molecule is called a blunt end. In a blunt-ended molecule both strands terminate in a base pair. Blunt ends are not always desired in biotechnology since when using a DNA ligase to join two molecules into one, the yield is significantly lower with blunt ends. When performing subcloning, it also has the disadvantage of potentially inserting the insert DNA in the opposite orientation desired. On the other hand, blunt ends are always compatible with each other. Here is an example of a small piece of blunt-ended DNA:
## Overhangs and sticky ends
Non-blunt ends are created by various overhangs. An overhang is a stretch of unpaired nucleotides in the end of a DNA molecule. These unpaired nucleotides can be in either strand, creating either 3' or 5' overhangs.
The simplest case of an overhang is a single nucleotide. This is most often adenosine and is created as a 3' overhang by some DNA polymerases. Most commonly this is used in cloning PCR products created by such an enzyme. The product is joined with a linear DNA molecule with 5' thymine overhangs. Since adenine and thymine form a base pair, this facilitates the joining of the two molecules by a ligase, yielding a circular molecule. Here is an example of an A-overhang:
Longer overhangs are called cohesive ends or sticky ends. They are most often created by restriction endonucleases when they cut DNA. Very often they cut the two DNA strands four base pairs from each other, creating a four-base 3' overhang in the other molecule and a complementary 5' overhang in the other. These ends are called cohesive since they are easily joined back together by a ligase. Also, since different restriction endonucleases usually create different overhangs, it is possible cut a piece of DNA with two different enzymes and the join it with another DNA molecule with ends created by the same enzymes. Since the overhangs have to be complementary in order for the ligase to work, the two molecules can only join in one orientation. This is often highly desirable in molecular biology.
For example, these two "sticky" ends are compatible:
They can form complementary base pairs in the overhang region: | DNA end
# Overview
DNA end or sticky end refers to the properties of the end of a molecule of DNA. The concept is important in molecular biology, especially in cloning or when subcloning insert DNA into vector DNA. All the terms can also be used in reference to RNA.
# Single-stranded DNA molecules
A single-stranded non-circular DNA molecule has two non-identical ends, the 3' end and the 5' end (usually pronounced "three prime end" and "five prime end". The numbers refer to the numbering of carbon atoms in the deoxyribose, which is a sugar forming an important part of the backbone of the DNA molecule. In the backbone of DNA the 5' carbon of one deoxyribose is linked to the 3' carbon of another by a phosphate group. The 5' carbon of this deoxyribose is again linked to the 3' carbon of the next, and so forth.
# Variations in double-stranded molecules
When a molecule of DNA is double stranded, as DNA usually is, the two strands run in opposite directions. Therefore, one end of the molecule will have the 3' end of strand 1 and the 5' end of strand 2, and vice versa in the other end. However, the fact that the molecule is two stranded allows numerous different variations.
## Blunt ends
The simplest DNA end of a double stranded molecule is called a blunt end. In a blunt-ended molecule both strands terminate in a base pair. Blunt ends are not always desired in biotechnology since when using a DNA ligase to join two molecules into one, the yield is significantly lower with blunt ends. When performing subcloning, it also has the disadvantage of potentially inserting the insert DNA in the opposite orientation desired. On the other hand, blunt ends are always compatible with each other. Here is an example of a small piece of blunt-ended DNA:
## Overhangs and sticky ends
Non-blunt ends are created by various overhangs. An overhang is a stretch of unpaired nucleotides in the end of a DNA molecule. These unpaired nucleotides can be in either strand, creating either 3' or 5' overhangs.
The simplest case of an overhang is a single nucleotide. This is most often adenosine and is created as a 3' overhang by some DNA polymerases. Most commonly this is used in cloning PCR products created by such an enzyme. The product is joined with a linear DNA molecule with 5' thymine overhangs. Since adenine and thymine form a base pair, this facilitates the joining of the two molecules by a ligase, yielding a circular molecule. Here is an example of an A-overhang:
Longer overhangs are called cohesive ends or sticky ends. They are most often created by restriction endonucleases when they cut DNA. Very often they cut the two DNA strands four base pairs from each other, creating a four-base 3' overhang in the other molecule and a complementary 5' overhang in the other. These ends are called cohesive since they are easily joined back together by a ligase. Also, since different restriction endonucleases usually create different overhangs, it is possible cut a piece of DNA with two different enzymes and the join it with another DNA molecule with ends created by the same enzymes. Since the overhangs have to be complementary in order for the ligase to work, the two molecules can only join in one orientation. This is often highly desirable in molecular biology.
For example, these two "sticky" ends are compatible:
They can form complementary base pairs in the overhang region: | https://www.wikidoc.org/index.php/Blunt_end | |
9e3d2d74d008d0d637bfe75bce270b39620fc338 | wikidoc | Entropy | Entropy
In thermodynamics (a branch of physics), entropy is a measure of the unavailability of a system’s energy to do work.
It is a measure of the randomness of molecules in a system and is central to the second law of thermodynamics and the combined law of thermodynamics, which deal with physical processes and whether they occur spontaneously. Spontaneous changes, in isolated systems, occur with an increase in entropy. Spontaneous changes tend to smooth out differences in temperature, pressure, density, and chemical potential that may exist in a system, and entropy is thus a measure of how far this smoothing-out process has progressed.
The word "entropy" is derived from the Greek εντροπία "a turning toward" (εν- "in" + τροπή "a turning"), and is symbolized by S in physics.
# Explanation
When a system's energy is defined as the sum of its "useful" energy, (e.g. that used to push a piston), and its "useless energy", i.e. that energy which cannot be used for external work, then entropy may be (most concretely) visualized as the "scrap" or "useless" energy whose energetic prevalence over the total energy of a system is directly proportional to the absolute temperature of the considered system. (Note the product "TS" in the Gibbs free energy or Helmholtz free energy relations).
Entropy is a function of a quantity of heat which shows the possibility of conversion of that heat into work. The increase in entropy is small when heat is added at high temperature and is greater when heat is added at lower temperature. Thus for maximum entropy there is minimum availability for conversion into work and for minimum entropy there is maximum availability for conversion into work.
Quantitatively, entropy is defined by the differential quantity dS = \delta Q/T, where \delta Q is the amount of heat absorbed in an isothermal and reversible process in which the system goes from one state to another, and T is the absolute temperature at which the process is occurring. Entropy is one of the factors that determines the free energy of the system. This thermodynamic definition of entropy is only valid for a system in equilibrium (because temperature is defined only for a system in equilibrium), while the statistical definition of entropy (see below) applies to any system. Thus the statistical definition is usually considered the fundamental definition of entropy.
Entropy increase has often been defined as a change to a more disordered state at a molecular level. In recent years, entropy has been interpreted in terms of the "dispersal" of energy. Entropy is an extensive state function that accounts for the effects of irreversibility in thermodynamic systems.
In terms of statistical mechanics, the entropy describes the number of the possible microscopic configurations of the system. The statistical definition of entropy is the more fundamental definition, from which all other definitions and all properties of entropy follow.
# Origin of concept
The first law of thermodynamics, formalized through the heat-friction experiments of James Joule in 1843, deals with the concept of energy, which is conserved in all processes; the first law, however, lacks in its ability to quantify the effects of friction and dissipation.
The concept of entropy was developed in the 1850s by German physicist Rudolf Clausius who described it as the transformation-content, i.e. dissipative energy use, of a thermodynamic system or working body of chemical species during a change of state.
Although the concept of entropy was originally a thermodynamic construct, it has been adapted in other fields of study, including information theory, psychodynamics, thermoeconomics, and evolution.
# History
The history of entropy begins with the work of French mathematician Lazare Carnot who in his 1803 paper Fundamental Principles of Equilibrium and Movement proposed that in any machine the accelerations and shocks of the moving parts all represent losses of moment of activity. In other words, in any natural process there exists an inherent tendency towards the dissipation of useful energy. Building on this work, in 1824 Lazare's son Sadi Carnot published Reflections on the Motive Power of Fire in which he set forth the view that in all heat-engines whenever "caloric", or what is now known as heat, falls through a temperature difference, that work or motive power can be produced from the actions of the "fall of caloric" between a hot and cold body. This was an early insight into the second law of thermodynamics.
Carnot based his views of heat partially on the early 18th century "Newtonian hypothesis" that both heat and light were types of indestructible forms of matter, which are attracted and repelled by other matter, and partially on the contemporary views of Count Rumford who showed in 1789 that heat could be created by friction as when cannon bores are machined. Accordingly, Carnot reasoned that if the body of the working substance, such as a body of steam, is brought back to its original state (temperature and pressure) at the end of a complete engine cycle, that "no change occurs in the condition of the working body." This latter comment was amended in his foot notes, and it was this comment that led to the development of entropy.
In the 1850s and 60s, German physicist Rudolf Clausius gravely objected to this latter supposition, i.e. that no change occurs in the working body, and gave this "change" a mathematical interpretation by questioning the nature of the inherent loss of usable heat when work is done, e.g. heat produced by friction. This was in contrast to earlier views, based on the theories of Isaac Newton, that heat was an indestructible particle that had mass. Later, scientists such as Ludwig Boltzmann, Josiah Willard Gibbs, and James Clerk Maxwell gave entropy a statistical basis. Carathéodory linked entropy with a mathematical definition of irreversibility, in terms of trajectories and integrability.
# Definitions and descriptions
In science, the term "entropy" is generally interpreted in three distinct, but semi-related, ways, i.e. from macroscopic viewpoint (classical thermodynamics), a microscopic viewpoint (statistical thermodynamics), and an information viewpoint (information theory).
The statistical definition of entropy (see below) is the fundamental definition because the other two can be mathematically derived from it, but not vice versa. All properties of entropy (including second law of thermodynamics) follow from this definition.
## Macroscopic viewpoint (classical thermodynamics)
In a thermodynamic system, a "universe" consisting of "surroundings" and "systems" and made up of quantities of matter, its pressure differences, density differences, and temperature differences all tend to equalize over time - simply because equilibrium state has higher probability (more possible combinations of microstates) than any other - see statistical mechanics. In the ice melting example, the difference in temperature between a warm room (the surroundings) and cold glass of ice and water (the system and not part of the room), begins to be equalized as portions of the heat energy from the warm surroundings spread out to the cooler system of ice and water.
Over time the temperature of the glass and its contents and the temperature of the room become equal. The entropy of the room has decreased as some of its energy has been dispersed to the ice and water. However, as calculated in the example, the entropy of the system of ice and water has increased more than the entropy of the surrounding room has decreased. In an isolated system such as the room and ice water taken together, the dispersal of energy from warmer to cooler always results in a net increase in entropy. Thus, when the 'universe' of the room and ice water system has reached a temperature equilibrium, the entropy change from the initial state is at a maximum. The entropy of the thermodynamic system is a measure of how far the equalization has progressed.
A special case of entropy increase, the entropy of mixing, occurs when two or more different substances are mixed. If the substances are at the same temperature and pressure, there will be no net exchange of heat or work - the entropy increase will be entirely due to the mixing of the different substances.
From a macroscopic perspective, in classical thermodynamics the entropy is interpreted simply as a state function of a thermodynamic system: that is, a property depending only on the current state of the system, independent of how that state came to be achieved. The state function has the important property that, when multiplied by a reference temperature, it can be understood as a measure of the amount of energy in a physical system that cannot be used to do thermodynamic work; i.e., work mediated by thermal energy. More precisely, in any process where the system gives up energy ΔE, and its entropy falls by ΔS, a quantity at least TR ΔS of that energy must be given up to the system's surroundings as unusable heat (TR is the temperature of the system's external surroundings). Otherwise the process will not go forward.
In 1862, Clausius stated what he calls the “theorem respecting the equivalence-values of the transformations” or what is now known as the second law of thermodynamics, as such:
Quantitatively, Clausius states the mathematical expression for this theorem is as follows. Let δQ be an element of the heat given up by the body to any reservoir of heat during its own changes, heat which it may absorb from a reservoir being here reckoned as negative, and T the absolute temperature of the body at the moment of giving up this heat, then the equation:
must be true for every reversible cyclical process, and the relation:
must hold good for every cyclical process which is in any way possible. This is the essential formulation of the second law and one of the original forms of the concept of entropy. It can be seen that the dimensions of entropy are energy divided by temperature, which is the same as the dimensions of Boltzmann's constant (kB) and heat capacity. The SI unit of entropy is "joule per kelvin" (J·K−1). In this manner, the quantity "ΔS" is utilized as a type of internal energy, which accounts for the effects of irreversibility, in the energy balance equation for any given system. In the Gibbs free energy equation, i.e. ΔG = ΔH - TΔS, for example, which is a formula commonly utilized to determine if chemical reactions will occur, the energy related to entropy changes TΔS is subtracted from the "total" system energy ΔH to give the "free" energy ΔG of the system, as during a chemical process or as when a system changes state.
## Microscopic definition of entropy (statistical mechanics)
In statistical thermodynamics the entropy is defined as (proportional to) the logarithm of the number of microscopic configurations that result in the observed macroscopic description of the thermodynamic system:
where
This definition is considered to be the fundamental definition of entropy (as all other definitions can be mathematically derived from it, but not vice versa). In Boltzmann's 1896 Lectures on Gas Theory, he showed that this expression gives a measure of entropy for systems of atoms and molecules in the gas phase, thus providing a measure for the entropy of classical thermodynamics.
In 1877, Boltzmann visualized a probabilistic way to measure the entropy of an ensemble of ideal gas particles, in which he defined entropy to be proportional to the logarithm of the number of microstates such a gas could occupy. Henceforth, the essential problem in statistical thermodynamics, i.e. according to Erwin Schrödinger, has been to determine the distribution of a given amount of energy E over N identical systems.
Statistical mechanics explains entropy as the amount of uncertainty (or "mixedupness" in the phrase of Gibbs) which remains about a system, after its observable macroscopic properties have been taken into account. For a given set of macroscopic variables, like temperature and volume, the entropy measures the degree to which the probability of the system is spread out over different possible quantum states. The more states available to the system with higher probability, the greater the entropy. More specifically, entropy is a logarithmic measure of the density of states. In essence, the most general interpretation of entropy is as a measure of our uncertainty about a system. The equilibrium state of a system maximizes the entropy because we have lost all information about the initial conditions except for the conserved variables; maximizing the entropy maximizes our ignorance about the details of the system. This uncertainty is not of the everyday subjective kind, but rather the uncertainty inherent to the experimental method and interpretative model.
On the molecular scale, the two definitions match up because adding heat to a system, which increases its classical thermodynamic entropy, also increases the system's thermal fluctuations, so giving an increased lack of information about the exact microscopic state of the system, i.e. an increased statistical mechanical entropy.
The interpretative model has a central role in determining entropy. The qualifier "for a given set of macroscopic variables" above has very deep implications: if two observers use different sets of macroscopic variables, then they will observe different entropies. For example, if observer A uses the variables U, V and W, and observer B uses U, V, W, X, then, by changing X, observer B can cause an effect that looks like a violation of the second law of thermodynamics to observer A. In other words: the set of macroscopic variables one chooses must include everything that may change in the experiment, otherwise one might see decreasing entropy!
## Entropy in chemical thermodynamics
Thermodynamic entropy is central in chemical thermodynamics, enabling changes to be quantified and the outcome of reactions predicted. The second law of thermodynamics states that entropy in the combination of a system and its surroundings (or in an isolated system by itself) increases during all spontaneous chemical and physical processes. Spontaneity in chemistry means “by itself, or without any outside influence”, and has nothing to do with speed. The Clausius equation of δqrev/T = ΔS introduces the measurement of entropy change, ΔS. Entropy change describes the direction and quantitates the magnitude of simple changes such as heat transfer between systems – always from hotter to cooler spontaneously. Thus, when a mole of substance at 0 K is warmed by its surroundings to 298 K, the sum of the incremental values of qrev/T constitute each element's or compound's standard molar entropy, a fundamental physical property and an indicator of the amount of energy stored by a substance at 298 K. Entropy change also measures the mixing of substances as a summation of their relative quantities in the final mixture.
Entropy is equally essential in predicting the extent of complex chemical reactions, i.e. whether a process will go as written or proceed in the opposite direction. For such applications, ΔS must be incorporated in an expression that includes both the system and its surroundings, ΔSuniverse = ΔSsurroundings + ΔS system. This expression becomes, via some steps, the Gibbs free energy equation for reactants and products in the system: ΔG = ΔH −T ΔS .
## The second law
An important law of physics, the second law of thermodynamics, states that the total entropy of any isolated thermodynamic system tends to increase over time, approaching a maximum value; and so, by implication, the entropy of the universe (i.e. the system and its surroundings), assumed as an isolated system, tends to increase. Two important consequences are that heat cannot of itself pass from a colder to a hotter body: i.e., it is impossible to transfer heat from a cold to a hot reservoir without at the same time converting a certain amount of work to heat. It is also impossible for any device that can operate on a cycle to receive heat from a single reservoir and produce a net amount of work; it can only get useful work out of the heat if heat is at the same time transferred from a hot to a cold reservoir. This means that there is no possibility of an isolated "perpetual motion" system. Also, from this it follows that a reduction in the increase of entropy in a specified process, such as a chemical reaction, means that it is energetically more efficient.
In general, according to the second law, the entropy of a system that is not isolated may decrease. An air conditioner, for example, cools the air in a room, thus reducing the entropy of the air. The heat, however, involved in operating the air conditioner always makes a bigger contribution to the entropy of the environment than the decrease of the entropy of the air. Thus the total entropy of the room and the environment increases, in agreement with the second law.
## Entropy balance equation for open systems
In chemical engineering, the principles of thermodynamics are commonly applied to "open systems", i.e. those in which heat, work, and mass flow across the system boundary. In a system in which there are flows of both heat (\dot{Q}) and work, i.e. \dot{W}_S (shaft work) and P(dV/dt) (pressure-volume work), across the system boundaries, the heat flow, but not the work flow, causes a change in the entropy of the system. This rate of entropy change is \dot{Q}/T, where T is the absolute thermodynamic temperature of the system at the point of the heat flow. If, in addition, there are mass flows across the system boundaries, the total entropy of the system will also change due to this convected flow.
To derive a generalized entropy balanced equation, we start with the general balance equation for the change in any extensive quantity Θ in a thermodynamic system, a quantity that may be either conserved, such as energy, or non-conserved, such as entropy. The basic generic balance expression states that dΘ/dt, i.e. the rate of change of Θ in the system, equals the rate at which Θ enters the system at the boundaries, minus the rate at which Θ leaves the system across the system boundaries, plus the rate at which Θ is generated within the system. Using this generic balance equation, with respect to the rate of change with time of the extensive quantity entropy S, the entropy balance equation for an open thermodynamic system is:
where
Note, also, that if there are multiple heat flows, the term \dot{Q}/T is to be replaced by \sum \dot{Q}_j/T_j, where \dot{Q}_j is the heat flow and T_j is the temperature at the jth heat flow port into the system.
## Entropy in quantum mechanics (von Neumann entropy)
In quantum statistical mechanics, the concept of entropy was developed by John von Neumann and is generally referred to as "von Neumann entropy". Von Neumann established a rigorous mathematical framework for quantum mechanics with his work Mathematische Grundlagen der Quantenmechanik. He provided in this work a theory of measurement, where the usual notion of wave collapse is described as an irreversible process (the so called von Neumann or projective measurement). Using this concept, in conjunction with the density matrix he extended the classical concept of entropy into the quantum domain.
It is well known that a Shannon based definition of information entropy leads in the classical case to the Boltzmann entropy. It is tempting to regard the Von Neumann entropy as the corresponding quantum mechanical definition. But the latter is problematic from quantum information point of view. Consequently Stotland, Pomeransky, Bachmat and Cohen have introduced a new definition of entropy that reflects the inherent uncertainty of quantum mechanical states. This definition allows to distinguish between the minimum uncertainty entropy of pure states, and the excess statistical entropy of mixtures.
# Entropy in Astrophysics
In astrophysics, what is referred to as "entropy" is actually the adiabatic constant derived as follows.
Using the first law of thermodynamics for a quasi-static, infinitesimal process for a hydrostatic system
For an ideal gas in this special case, the internal energy, U, is only a function of T; therefore the partial derivative of heat capacity with respect to T is identically the same as the full derivative, yielding through some manipulation
dQ = C_{V} dT+P dV.
Further manipulation using the differential version of the ideal gas law, the previous equation, and assuming constant pressure, one finds
dQ = C_{P} dT-V dP.
For an adiabatic process dQ=0 and recalling \gamma = \frac{C_{P}}{C_{V}}, one finds
One can solve this simple differential equation to find
PV^{\gamma} = constant = K
This equation is known as an expression for the adiabatic constant, K, also called the adiabat. From the ideal gas equation one also knows
P=\frac{\rho k_{B}T}{\mu m_{H}},
where k_{B} is Boltzmann's constant.
Substituting this into the above equation along with V=/\rho and \gamma = 5/3 for an ideal monoatomic gas one finds
K = \frac{k_{B}T}{\mu m_{H} \rho^{2/3}},
where \mu is the mean molecular weight of the gas or plasma; and m_{H} is the mass of the Hydrogen atom, which is extremely close to the mass of the proton, m_{p}, the quantity more often used in astrophysical theory of galaxy clusters.
This is what astrophysicists refer to as "entropy" and has units of . This quantity relates to the thermodynamic entropy as
S = k_{B}\, ln \Omega + S_{0}
where \Omega, the density of states in statistical theory, takes on the value of K as defined above.
## Standard textbook definitions
The following is a list of definitions of entropy from a collection of textbooks. Note that textbook definitions are not always the most helpful definitions, but they are an important aspect of the culture surrounding the concept of entropy.
- Entropy – energy broken down in irretrievable heat.
- Boltzmann's constant times the logarithm of a multiplicity; where the multiplicity of a macrostate is the number of microstates that correspond to the macrostate.
- the number of ways of arranging things in a system (times the Boltzmann's constant).
- a non-conserved thermodynamic state function, measured in terms of the number of microstates a system can assume, which corresponds to a degradation in usable energy.
- a direct measure of the randomness of a system.
- a measure of energy dispersal at a specific temperature.
- a measure of the partial loss of the ability of a system to perform work due to the effects of irreversibility.
- an index of the tendency of a system towards spontaneous change.
- a measure of the unavailability of a system’s energy to do work; also a measure of disorder; the higher the entropy the greater the disorder.
- a parameter representing the state of disorder of a system at the atomic, ionic, or molecular level.
- a measure of disorder in the universe or of the availability of the energy in a system to do work.
# Approaches to understanding entropy
## Order and disorder
Entropy, historically, has often been associated with the amount of order, disorder, and/or chaos in a thermodynamic system. The traditional definition of entropy is that it refers to changes in the status quo of the system and is a measure of "molecular disorder" and the amount of wasted energy in a dynamical energy transformation from one state or form to another. In this direction, a number of authors, in recent years, have derived exact entropy formulas to account for and measure disorder and order in atomic and molecular assemblies. One of the simpler entropy order/disorder formulas is that derived in 1984 by thermodynamic physicist Peter Landsberg, which is based on a combination of thermodynamics and information theory arguments. Landsberg argues that when constraints operate on a system, such that it is prevented from entering one or more of its possible or permitted states, as contrasted with its forbidden states, the measure of the total amount of “disorder” in the system is given by the following expression:
Similarly, the total amount of "order" in the system is given by:
In which CD is the "disorder" capacity of the system, which is the entropy of the parts contained in the permitted ensemble, CI is the "information" capacity of the system, an expression similar to Shannon's channel capacity, and CO is the "order" capacity of the system.
## Energy dispersal
The concept of entropy can be described qualitatively as a measure of energy dispersal at a specific temperature. Similar terms have been in use from early in the history of classical thermodynamics, and with the development of statistical thermodynamics and quantum theory, entropy changes have been described in terms of the mixing or "spreading" of the total energy of each constituent of a system over its particular quantized energy levels.
Ambiguities in the terms disorder and chaos, which usually have meanings directly opposed to equilibrium, contribute to widespread confusion and hamper comprehension of entropy for most students. As the second law of thermodynamics shows, in an isolated system internal portions at different temperatures will tend to adjust to a single uniform temperature and thus produce equilibrium. A recently developed educational approach avoids ambiguous terms and describes such spreading out of energy as dispersal, which leads to loss of the differentials required for work even though the total energy remains constant in accordance with the first law of thermodynamics. Physical chemist Peter Atkins, for example, who previously wrote of dispersal leading to a disordered state, now writes that "spontaneous changes are always accompanied by a dispersal of energy", and has discarded 'disorder' as a description.
## Entropy and Information theory
In information theory, entropy is the measure of the amount of information that is missing before reception and is sometimes referred to as Shannon entropy. Shannon entropy is a broad and general concept which finds applications in information theory as well as thermodynamics. It was originally devised by Claude Shannon in 1948 to study the amount of information in a transmitted message. The definition of the information entropy is, however, quite general, and is expressed in terms of a discrete set of probabilities p_i. In the case of transmitted messages, these probabilities were the probabilities that a particular message was actually transmitted, and the entropy of the message system was a measure of how much information was in the message. For the case of equal probabilities (i.e. each message is equally probable), the Shannon entropy (in bits) is just the number of yes/no questions needed to determine the content of the message.
The question of the link between information entropy and thermodynamic entropy is a hotly debated topic. Some authors argue that there is a link between the two, while others will argue that they have absolutely nothing to do with each other.
The expressions for the two entropies are very similar. The information entropy H for equal probabilities p_i=p is:
where K is a constant which determines the units of entropy. For example, if the units are bits, then K=1/ln(2). The thermodynamic entropy S , from a statistical mechanical point of view was first expressed by Boltzmann:
where p is the probability of a system being in a particular microstate, given that it is in a particular macrostate, and k is Boltzmann's constant. It can be seen that one may think of the thermodynamic entropy as Boltzmann's constant, divided by ln(2), times the number of yes/no questions that must be asked in order to determine the microstate of the system, given that we know the macrostate. The link between thermodynamic and information entropy was developed in a series of papers by Edwin Jaynes beginning in 1957.
The problem with linking thermodynamic entropy to information entropy is that in information entropy the entire body of thermodynamics which deals with the physical nature of entropy is missing. The second law of thermodynamics which governs the behavior of thermodynamic systems in equilibrium, and the first law which expresses heat energy as the product of temperature and entropy are physical concepts rather than informational concepts. If thermodynamic entropy is seen as including all of the physical dynamics of entropy as well as the equilibrium statistical aspects, then information entropy gives only part of the description of thermodynamic entropy. Some authors, like Tom Schneider, argue for dropping the word entropy for the H function of information theory and using Shannon's other term "uncertainty" instead.
## Ice melting example
The illustration for this article is a classic example in which entropy increases in a small 'universe', a thermodynamic system consisting of the 'surroundings' (the warm room) and 'system' (glass, ice, cold water). In this universe, some heat energy δQ from the warmer room surroundings (at 298 K or 25 °C) will spread out to the cooler system of ice and water at its constant temperature T of 273 K (0 °C), the melting temperature of ice. The entropy of the system will change by the amount dS = δQ/T, in this example δQ/273 K. (The heat δQ for this process is the energy required to change water from the solid state to the liquid state, and is called the enthalpy of fusion, i.e. the ΔH for ice fusion.) The entropy of the surroundings will change by an amount dS = −δQ/298 K. So in this example, the entropy of the system increases, whereas the entropy of the surroundings decreases.
It is important to realize that the decrease in the entropy of the surrounding room is less than the increase in the entropy of the ice and water: the room temperature of 298 K is larger than 273 K and therefore the ratio, (entropy change), of δQ/298 K for the surroundings is smaller than the ratio (entropy change), of δQ/273 K for the ice+water system. To find the entropy change of our "universe", we add up the entropy changes for its constituents: the surrounding room, and the ice+water. The total entropy change is positive; this is always true in spontaneous events in a thermodynamic system and it shows the predictive importance of entropy: the final net entropy after such an event is always greater than was the initial entropy.
As the temperature of the cool water rises to that of the room and the room further cools imperceptibly, the sum of the δQ/T over the continuous range, at many increments, in the initially cool to finally warm water can be found by calculus. The entire miniature "universe", i.e. this thermodynamic system, has increased in entropy. Energy has spontaneously become more dispersed and spread out in that "universe" than when the glass of ice water was introduced and became a "system" within it.
# Topics in entropy
## Entropy and life
For over a century and a half, beginning with Clausius' 1863 memoir "On the Concentration of Rays of Heat and Light, and on the Limits of its Action", much writing and research has been devoted to the relationship between thermodynamic entropy and the evolution of life. The argument that life feeds on negative entropy or negentropy as put forth in the 1944 book What is Life? by physicist Erwin Schrödinger served as a further stimulus to this research. Recent writings have utilized the concept of Gibbs free energy to elaborate on this issue. Tangentially, some creationists have argued that entropy rules out evolution.
In the popular 1982 textbook Principles of Biochemistry by noted American biochemist Albert Lehninger, for example, it is argued that the order produced within cells as they grow and divide is more than compensated for by the disorder they create in their surroundings in the course of growth and division. In short, according to Lehninger, "living organisms preserve their internal order by taking from their surroundings free energy, in the form of nutrients or sunlight, and returning to their surroundings an equal amount of energy as heat and entropy."
Evolution related definitions:
- Negentropy - a shorthand colloquial phrase for negative entropy.
- Ectropy - a measure of the tendency of a dynamical system to do useful work and grow more organized.
- Syntropy - a tendency towards order and symmetrical combinations and designs of ever more advantageous and orderly patterns.
- Extropy – a metaphorical term defining the extent of a living or organizational system's intelligence, functional order, vitality, energy, life, experience, and capacity and drive for improvement and growth.
- Ecological entropy - a measure of biodiversity in the study of biological ecology.
## The arrow of time
Entropy is the only quantity in the physical sciences that "picks" a particular direction for time, sometimes called an arrow of time. As we go "forward" in time, the Second Law of Thermodynamics tells us that the entropy of an isolated system can only increase or remain the same; it cannot decrease. Hence, from one perspective, entropy measurement is thought of as a kind of clock.
## Entropy and cosmology
As a finite universe may be considered an isolated system, it may be subject to the Second Law of Thermodynamics, so that its total entropy is constantly increasing. It has been speculated that the universe is fated to a heat death in which all the energy ends up as a homogeneous distribution of thermal energy, so that no more work can be extracted from any source.
If the universe can be considered to have generally increasing entropy, then - as Roger Penrose has pointed out - gravity plays an important role in the increase because gravity causes dispersed matter to accumulate into stars, which collapse eventually into black holes. Jacob Bekenstein and Stephen Hawking have shown that black holes have the maximum possible entropy of any object of equal size. This makes them likely end points of all entropy-increasing processes, if they are totally effective matter and energy traps. Hawking has, however, recently changed his stance on this aspect.
The role of entropy in cosmology remains a controversial subject. Recent work has cast extensive doubt on the heat death hypothesis and the applicability of any simple thermodynamic model to the universe in general. Although entropy does increase in the model of an expanding universe, the maximum possible entropy rises much more rapidly - thus entropy density is decreasing with time. This results in an "entropy gap" pushing the system further away from equilibrium. Other complicating factors, such as the energy density of the vacuum and macroscopic quantum effects, are difficult to reconcile with thermodynamical models, making any predictions of large-scale thermodynamics extremely difficult.
## Miscellaneous definitions
- Entropy unit - a non-S.I. unit of thermodynamic entropy, usually denoted "e.u." and equal to one calorie per kelvin
- Gibbs entropy - the usual statistical mechanical entropy of a thermodynamic system.
- Boltzmann entropy - a type of Gibbs entropy, which neglects internal statistical correlations in the overall particle distribution.
- Tsallis entropy - a generalization of the standard Boltzmann-Gibbs entropy.
- Standard molar entropy - is the entropy content of one mole of substance, under conditions of standard temperature and pressure.
- Black hole entropy - is the entropy carried by a black hole, which is proportional to the surface area of the black hole's event horizon.
- Residual entropy - the entropy present after a substance is cooled arbitrarily close to absolute zero.
- Entropy of mixing - the change in the entropy when two different chemical substances or components are mixed.
- Loop entropy - is the entropy lost upon bringing together two residues of a polymer within a prescribed distance.
- Conformational entropy - is the entropy associated with the physical arrangement of a polymer chain that assumes a compact or globular state in solution.
- Entropic force - a microscopic force or reaction tendency related to system organization changes, molecular frictional considerations, and statistical variations.
- Free entropy - an entropic thermodynamic potential analogous to the free energy.
- Entropic explosion – an explosion in which the reactants undergo a large change in volume without releasing a large amount of heat.
- Entropy change – a change in entropy dS between two equilibrium states is given by the heat transferred dQrev divided by the absolute temperature T of the system in this interval.
- Sackur-Tetrode entropy - the entropy of a monatomic classical ideal gas determined via quantum considerations.
# Other relations
## Other mathematical definitions
- Kolmogorov-Sinai entropy - a mathematical type of entropy in dynamical systems related to measures of partitions.
- Topological entropy - a way of defining entropy in an iterated function map in ergodic theory.
- Relative entropy - is a natural distance measure from a "true" probability distribution P to an arbitrary probability distribution Q.
- Rényi entropy - a generalized entropy measure for fractal systems.
## Sociological definitions
The concept of entropy has also entered the domain of sociology, generally as a metaphor for chaos, disorder or dissipation of energy, rather than as a direct measure of thermodynamic or information entropy:
- Entropology – the study or discussion of entropy or the name sometimes given to thermodynamics without differential equations.
- Psychological entropy - the distribution of energy in the psyche, which tends to seek equilibrium or balance among all the structures of the psyche.
- Economic entropy – a semi-quantitative measure of the irrevocable dissipation and degradation of natural materials and available energy with respect to economic activity.
- Social entropy – a measure of social system structure, having both theoretical and statistical interpretations, i.e. society (macrosocietal variables) measured in terms of how the individual functions in society (microsocietal variables); also related to social equilibrium.
- Corporate entropy - energy waste as red tape and business team inefficiency, i.e. energy lost to waste. (This definition is comparable to von Clausewitz's concept of friction in war.)
# Quotes | Entropy
Template:Otheruses4
Template:Seeintro
Template:Cleanup-jargon
Template:EntropySegments
In thermodynamics (a branch of physics), entropy is a measure of the unavailability of a system’s energy to do work.[3][4]
It is a measure of the randomness of molecules in a system and is central to the second law of thermodynamics and the combined law of thermodynamics, which deal with physical processes and whether they occur spontaneously. Spontaneous changes, in isolated systems, occur with an increase in entropy. Spontaneous changes tend to smooth out differences in temperature, pressure, density, and chemical potential that may exist in a system, and entropy is thus a measure of how far this smoothing-out process has progressed.
The word "entropy" is derived from the Greek εντροπία "a turning toward" (εν- "in" + τροπή "a turning"), and is symbolized by S in physics.
# Explanation
When a system's energy is defined as the sum of its "useful" energy, (e.g. that used to push a piston), and its "useless energy", i.e. that energy which cannot be used for external work, then entropy may be (most concretely) visualized as the "scrap" or "useless" energy whose energetic prevalence over the total energy of a system is directly proportional to the absolute temperature of the considered system. (Note the product "TS" in the Gibbs free energy or Helmholtz free energy relations).
Entropy is a function of a quantity of heat which shows the possibility of conversion of that heat into work. The increase in entropy is small when heat is added at high temperature and is greater when heat is added at lower temperature. Thus for maximum entropy there is minimum availability for conversion into work and for minimum entropy there is maximum availability for conversion into work.
Quantitatively, entropy is defined by the differential quantity <math>dS = \delta Q/T</math>, where <math>\delta Q</math> is the amount of heat absorbed in an isothermal and reversible process in which the system goes from one state to another, and T is the absolute temperature at which the process is occurring.[5] Entropy is one of the factors that determines the free energy of the system. This thermodynamic definition of entropy is only valid for a system in equilibrium (because temperature is defined only for a system in equilibrium), while the statistical definition of entropy (see below) applies to any system. Thus the statistical definition is usually considered the fundamental definition of entropy.
Entropy increase has often been defined as a change to a more disordered state at a molecular level. In recent years, entropy has been interpreted in terms of the "dispersal" of energy. Entropy is an extensive state function that accounts for the effects of irreversibility in thermodynamic systems.
In terms of statistical mechanics, the entropy describes the number of the possible microscopic configurations of the system. The statistical definition of entropy is the more fundamental definition, from which all other definitions and all properties of entropy follow.
# Origin of concept
The first law of thermodynamics, formalized through the heat-friction experiments of James Joule in 1843, deals with the concept of energy, which is conserved in all processes; the first law, however, lacks in its ability to quantify the effects of friction and dissipation.
The concept of entropy was developed in the 1850s by German physicist Rudolf Clausius who described it as the transformation-content, i.e. dissipative energy use, of a thermodynamic system or working body of chemical species during a change of state.[6]
Although the concept of entropy was originally a thermodynamic construct, it has been adapted in other fields of study, including information theory, psychodynamics, thermoeconomics, and evolution.[7][8][9]
# History
The history of entropy begins with the work of French mathematician Lazare Carnot who in his 1803 paper Fundamental Principles of Equilibrium and Movement proposed that in any machine the accelerations and shocks of the moving parts all represent losses of moment of activity. In other words, in any natural process there exists an inherent tendency towards the dissipation of useful energy. Building on this work, in 1824 Lazare's son Sadi Carnot published Reflections on the Motive Power of Fire in which he set forth the view that in all heat-engines whenever "caloric", or what is now known as heat, falls through a temperature difference, that work or motive power can be produced from the actions of the "fall of caloric" between a hot and cold body. This was an early insight into the second law of thermodynamics.[citation needed]
Carnot based his views of heat partially on the early 18th century "Newtonian hypothesis" that both heat and light were types of indestructible forms of matter, which are attracted and repelled by other matter, and partially on the contemporary views of Count Rumford who showed in 1789 that heat could be created by friction as when cannon bores are machined.[10] Accordingly, Carnot reasoned that if the body of the working substance, such as a body of steam, is brought back to its original state (temperature and pressure) at the end of a complete engine cycle, that "no change occurs in the condition of the working body." This latter comment was amended in his foot notes, and it was this comment that led to the development of entropy.[citation needed]
In the 1850s and 60s, German physicist Rudolf Clausius gravely objected to this latter supposition, i.e. that no change occurs in the working body, and gave this "change" a mathematical interpretation by questioning the nature of the inherent loss of usable heat when work is done, e.g. heat produced by friction.[6] This was in contrast to earlier views, based on the theories of Isaac Newton, that heat was an indestructible particle that had mass. Later, scientists such as Ludwig Boltzmann, Josiah Willard Gibbs, and James Clerk Maxwell gave entropy a statistical basis. Carathéodory linked entropy with a mathematical definition of irreversibility, in terms of trajectories and integrability.
# Definitions and descriptions
In science, the term "entropy" is generally interpreted in three distinct, but semi-related, ways, i.e. from macroscopic viewpoint (classical thermodynamics), a microscopic viewpoint (statistical thermodynamics), and an information viewpoint (information theory).
The statistical definition of entropy (see below) is the fundamental definition because the other two can be mathematically derived from it, but not vice versa. All properties of entropy (including second law of thermodynamics) follow from this definition.
## Macroscopic viewpoint (classical thermodynamics)
Template:Conjugate variables (thermodynamics)
In a thermodynamic system, a "universe" consisting of "surroundings" and "systems" and made up of quantities of matter, its pressure differences, density differences, and temperature differences all tend to equalize over time - simply because equilibrium state has higher probability (more possible combinations of microstates) than any other - see statistical mechanics. In the ice melting example, the difference in temperature between a warm room (the surroundings) and cold glass of ice and water (the system and not part of the room), begins to be equalized as portions of the heat energy from the warm surroundings spread out to the cooler system of ice and water.
Over time the temperature of the glass and its contents and the temperature of the room become equal. The entropy of the room has decreased as some of its energy has been dispersed to the ice and water. However, as calculated in the example, the entropy of the system of ice and water has increased more than the entropy of the surrounding room has decreased. In an isolated system such as the room and ice water taken together, the dispersal of energy from warmer to cooler always results in a net increase in entropy. Thus, when the 'universe' of the room and ice water system has reached a temperature equilibrium, the entropy change from the initial state is at a maximum. The entropy of the thermodynamic system is a measure of how far the equalization has progressed.
A special case of entropy increase, the entropy of mixing, occurs when two or more different substances are mixed. If the substances are at the same temperature and pressure, there will be no net exchange of heat or work - the entropy increase will be entirely due to the mixing of the different substances.[11]
From a macroscopic perspective, in classical thermodynamics the entropy is interpreted simply as a state function of a thermodynamic system: that is, a property depending only on the current state of the system, independent of how that state came to be achieved. The state function has the important property that, when multiplied by a reference temperature, it can be understood as a measure of the amount of energy in a physical system that cannot be used to do thermodynamic work; i.e., work mediated by thermal energy. More precisely, in any process where the system gives up energy ΔE, and its entropy falls by ΔS, a quantity at least TR ΔS of that energy must be given up to the system's surroundings as unusable heat (TR is the temperature of the system's external surroundings). Otherwise the process will not go forward.
In 1862, Clausius stated what he calls the “theorem respecting the equivalence-values of the transformations” or what is now known as the second law of thermodynamics, as such:
Quantitatively, Clausius states the mathematical expression for this theorem is as follows. Let δQ be an element of the heat given up by the body to any reservoir of heat during its own changes, heat which it may absorb from a reservoir being here reckoned as negative, and T the absolute temperature of the body at the moment of giving up this heat, then the equation:
must be true for every reversible cyclical process, and the relation:
must hold good for every cyclical process which is in any way possible. This is the essential formulation of the second law and one of the original forms of the concept of entropy. It can be seen that the dimensions of entropy are energy divided by temperature, which is the same as the dimensions of Boltzmann's constant (kB) and heat capacity. The SI unit of entropy is "joule per kelvin" (J·K−1). In this manner, the quantity "ΔS" is utilized as a type of internal energy, which accounts for the effects of irreversibility, in the energy balance equation for any given system. In the Gibbs free energy equation, i.e. ΔG = ΔH - TΔS, for example, which is a formula commonly utilized to determine if chemical reactions will occur, the energy related to entropy changes TΔS is subtracted from the "total" system energy ΔH to give the "free" energy ΔG of the system, as during a chemical process or as when a system changes state.
## Microscopic definition of entropy (statistical mechanics)
In statistical thermodynamics the entropy is defined as (proportional to) the logarithm of the number of microscopic configurations that result in the observed macroscopic description of the thermodynamic system:
where
This definition is considered to be the fundamental definition of entropy (as all other definitions can be mathematically derived from it, but not vice versa). In Boltzmann's 1896 Lectures on Gas Theory, he showed that this expression gives a measure of entropy for systems of atoms and molecules in the gas phase, thus providing a measure for the entropy of classical thermodynamics.
In 1877, Boltzmann visualized a probabilistic way to measure the entropy of an ensemble of ideal gas particles, in which he defined entropy to be proportional to the logarithm of the number of microstates such a gas could occupy. Henceforth, the essential problem in statistical thermodynamics, i.e. according to Erwin Schrödinger, has been to determine the distribution of a given amount of energy E over N identical systems.
Statistical mechanics explains entropy as the amount of uncertainty (or "mixedupness" in the phrase of Gibbs) which remains about a system, after its observable macroscopic properties have been taken into account. For a given set of macroscopic variables, like temperature and volume, the entropy measures the degree to which the probability of the system is spread out over different possible quantum states. The more states available to the system with higher probability, the greater the entropy. More specifically, entropy is a logarithmic measure of the density of states. In essence, the most general interpretation of entropy is as a measure of our uncertainty about a system. The equilibrium state of a system maximizes the entropy because we have lost all information about the initial conditions except for the conserved variables; maximizing the entropy maximizes our ignorance about the details of the system.[12] This uncertainty is not of the everyday subjective kind, but rather the uncertainty inherent to the experimental method and interpretative model.
On the molecular scale, the two definitions match up because adding heat to a system, which increases its classical thermodynamic entropy, also increases the system's thermal fluctuations, so giving an increased lack of information about the exact microscopic state of the system, i.e. an increased statistical mechanical entropy.
The interpretative model has a central role in determining entropy. The qualifier "for a given set of macroscopic variables" above has very deep implications: if two observers use different sets of macroscopic variables, then they will observe different entropies. For example, if observer A uses the variables U, V and W, and observer B uses U, V, W, X, then, by changing X, observer B can cause an effect that looks like a violation of the second law of thermodynamics to observer A. In other words: the set of macroscopic variables one chooses must include everything that may change in the experiment, otherwise one might see decreasing entropy![13]
## Entropy in chemical thermodynamics
Thermodynamic entropy is central in chemical thermodynamics, enabling changes to be quantified and the outcome of reactions predicted. The second law of thermodynamics states that entropy in the combination of a system and its surroundings (or in an isolated system by itself) increases during all spontaneous chemical and physical processes. Spontaneity in chemistry means “by itself, or without any outside influence”, and has nothing to do with speed. The Clausius equation of δqrev/T = ΔS introduces the measurement of entropy change, ΔS. Entropy change describes the direction and quantitates the magnitude of simple changes such as heat transfer between systems – always from hotter to cooler spontaneously.[14] Thus, when a mole of substance at 0 K is warmed by its surroundings to 298 K, the sum of the incremental values of qrev/T constitute each element's or compound's standard molar entropy, a fundamental physical property and an indicator of the amount of energy stored by a substance at 298 K.[15][16] Entropy change also measures the mixing of substances as a summation of their relative quantities in the final mixture.[17]
Entropy is equally essential in predicting the extent of complex chemical reactions, i.e. whether a process will go as written or proceed in the opposite direction. For such applications, ΔS must be incorporated in an expression that includes both the system and its surroundings, ΔSuniverse = ΔSsurroundings + ΔS system. This expression becomes, via some steps, the Gibbs free energy equation for reactants and products in the system: ΔG [the Gibbs free energy change of the system] = ΔH [the enthalpy change] −T ΔS [the entropy change].[15]
## The second law
An important law of physics, the second law of thermodynamics, states that the total entropy of any isolated thermodynamic system tends to increase over time, approaching a maximum value; and so, by implication, the entropy of the universe (i.e. the system and its surroundings), assumed as an isolated system, tends to increase. Two important consequences are that heat cannot of itself pass from a colder to a hotter body: i.e., it is impossible to transfer heat from a cold to a hot reservoir without at the same time converting a certain amount of work to heat. It is also impossible for any device that can operate on a cycle to receive heat from a single reservoir and produce a net amount of work; it can only get useful work out of the heat if heat is at the same time transferred from a hot to a cold reservoir. This means that there is no possibility of an isolated "perpetual motion" system. Also, from this it follows that a reduction in the increase of entropy in a specified process, such as a chemical reaction, means that it is energetically more efficient.
In general, according to the second law, the entropy of a system that is not isolated may decrease. An air conditioner, for example, cools the air in a room, thus reducing the entropy of the air. The heat, however, involved in operating the air conditioner always makes a bigger contribution to the entropy of the environment than the decrease of the entropy of the air. Thus the total entropy of the room and the environment increases, in agreement with the second law.
## Entropy balance equation for open systems
In chemical engineering, the principles of thermodynamics are commonly applied to "open systems", i.e. those in which heat, work, and mass flow across the system boundary. In a system in which there are flows of both heat (<math>\dot{Q}</math>) and work, i.e. <math>\dot{W}_S</math> (shaft work) and P(dV/dt) (pressure-volume work), across the system boundaries, the heat flow, but not the work flow, causes a change in the entropy of the system. This rate of entropy change is <math>\dot{Q}/T,</math> where T is the absolute thermodynamic temperature of the system at the point of the heat flow. If, in addition, there are mass flows across the system boundaries, the total entropy of the system will also change due to this convected flow.
To derive a generalized entropy balanced equation, we start with the general balance equation for the change in any extensive quantity Θ in a thermodynamic system, a quantity that may be either conserved, such as energy, or non-conserved, such as entropy. The basic generic balance expression states that dΘ/dt, i.e. the rate of change of Θ in the system, equals the rate at which Θ enters the system at the boundaries, minus the rate at which Θ leaves the system across the system boundaries, plus the rate at which Θ is generated within the system. Using this generic balance equation, with respect to the rate of change with time of the extensive quantity entropy S, the entropy balance equation for an open thermodynamic system is:[18]
where
Note, also, that if there are multiple heat flows, the term <math>\dot{Q}/T</math> is to be replaced by <math>\sum \dot{Q}_j/T_j,</math> where <math>\dot{Q}_j</math> is the heat flow and <math>T_j</math> is the temperature at the jth heat flow port into the system.
## Entropy in quantum mechanics (von Neumann entropy)
In quantum statistical mechanics, the concept of entropy was developed by John von Neumann and is generally referred to as "von Neumann entropy". Von Neumann established a rigorous mathematical framework for quantum mechanics with his work Mathematische Grundlagen der Quantenmechanik. He provided in this work a theory of measurement, where the usual notion of wave collapse is described as an irreversible process (the so called von Neumann or projective measurement). Using this concept, in conjunction with the density matrix he extended the classical concept of entropy into the quantum domain.
It is well known that a Shannon based definition of information entropy leads in the classical case to the Boltzmann entropy. It is tempting to regard the Von Neumann entropy as the corresponding quantum mechanical definition. But the latter is problematic from quantum information point of view. Consequently Stotland, Pomeransky, Bachmat and Cohen have introduced a new definition of entropy that reflects the inherent uncertainty of quantum mechanical states. This definition allows to distinguish between the minimum uncertainty entropy of pure states, and the excess statistical entropy of mixtures.[19]
# Entropy in Astrophysics
In astrophysics, what is referred to as "entropy" is actually the adiabatic constant derived as follows.
Using the first law of thermodynamics for a quasi-static, infinitesimal process for a hydrostatic system
For an ideal gas in this special case, the internal energy, U, is only a function of T; therefore the partial derivative of heat capacity with respect to T is identically the same as the full derivative, yielding through some manipulation
dQ = C_{V} dT+P dV.
</math>
Further manipulation using the differential version of the ideal gas law, the previous equation, and assuming constant pressure, one finds
dQ = C_{P} dT-V dP.
</math>
For an adiabatic process <math>dQ=0</math> and recalling <math>\gamma = \frac{C_{P}}{C_{V}}</math>, one finds
One can solve this simple differential equation to find
PV^{\gamma} = constant = K
</math>
This equation is known as an expression for the adiabatic constant, K, also called the adiabat. From the ideal gas equation one also knows
P=\frac{\rho k_{B}T}{\mu m_{H}},
</math>
where <math>k_{B}</math> is Boltzmann's constant.
Substituting this into the above equation along with <math>V=[grams]/\rho</math> and <math>\gamma = 5/3</math> for an ideal monoatomic gas one finds
K = \frac{k_{B}T}{\mu m_{H} \rho^{2/3}},
</math>
where <math>\mu</math> is the mean molecular weight of the gas or plasma; and <math>m_{H}</math> is the mass of the Hydrogen atom, which is extremely close to the mass of the proton, <math>m_{p}</math>, the quantity more often used in astrophysical theory of galaxy clusters.
This is what astrophysicists refer to as "entropy" and has units of [keV cm2]. This quantity relates to the thermodynamic entropy as
S = k_{B}\, ln \Omega + S_{0}
</math>
where <math>\Omega</math>, the density of states in statistical theory, takes on the value of K as defined above.
## Standard textbook definitions
The following is a list of definitions of entropy from a collection of textbooks. Note that textbook definitions are not always the most helpful definitions, but they are an important aspect of the culture surrounding the concept of entropy.
- Entropy – energy broken down in irretrievable heat.[20]
- Boltzmann's constant times the logarithm of a multiplicity; where the multiplicity of a macrostate is the number of microstates that correspond to the macrostate.[21]
- the number of ways of arranging things in a system (times the Boltzmann's constant).[22]
- a non-conserved thermodynamic state function, measured in terms of the number of microstates a system can assume, which corresponds to a degradation in usable energy.[23]
- a direct measure of the randomness of a system.[24]
- a measure of energy dispersal at a specific temperature.[25]
- a measure of the partial loss of the ability of a system to perform work due to the effects of irreversibility.[26]
- an index of the tendency of a system towards spontaneous change.[27]
- a measure of the unavailability of a system’s energy to do work; also a measure of disorder; the higher the entropy the greater the disorder.[28]
- a parameter representing the state of disorder of a system at the atomic, ionic, or molecular level.[29]
- a measure of disorder in the universe or of the availability of the energy in a system to do work.[30]
# Approaches to understanding entropy
## Order and disorder
Entropy, historically, has often been associated with the amount of order, disorder, and/or chaos in a thermodynamic system. The traditional definition of entropy is that it refers to changes in the status quo of the system and is a measure of "molecular disorder" and the amount of wasted energy in a dynamical energy transformation from one state or form to another.[31] In this direction, a number of authors, in recent years, have derived exact entropy formulas to account for and measure disorder and order in atomic and molecular assemblies.[32][9][33][34] One of the simpler entropy order/disorder formulas is that derived in 1984 by thermodynamic physicist Peter Landsberg, which is based on a combination of thermodynamics and information theory arguments. Landsberg argues that when constraints operate on a system, such that it is prevented from entering one or more of its possible or permitted states, as contrasted with its forbidden states, the measure of the total amount of “disorder” in the system is given by the following expression:[33][34]
Similarly, the total amount of "order" in the system is given by:
In which CD is the "disorder" capacity of the system, which is the entropy of the parts contained in the permitted ensemble, CI is the "information" capacity of the system, an expression similar to Shannon's channel capacity, and CO is the "order" capacity of the system.[9]
## Energy dispersal
The concept of entropy can be described qualitatively as a measure of energy dispersal at a specific temperature.[35] Similar terms have been in use from early in the history of classical thermodynamics, and with the development of statistical thermodynamics and quantum theory, entropy changes have been described in terms of the mixing or "spreading" of the total energy of each constituent of a system over its particular quantized energy levels.
Ambiguities in the terms disorder and chaos, which usually have meanings directly opposed to equilibrium, contribute to widespread confusion and hamper comprehension of entropy for most students.[36] As the second law of thermodynamics shows, in an isolated system internal portions at different temperatures will tend to adjust to a single uniform temperature and thus produce equilibrium. A recently developed educational approach avoids ambiguous terms and describes such spreading out of energy as dispersal, which leads to loss of the differentials required for work even though the total energy remains constant in accordance with the first law of thermodynamics.[37] Physical chemist Peter Atkins, for example, who previously wrote of dispersal leading to a disordered state, now writes that "spontaneous changes are always accompanied by a dispersal of energy", and has discarded 'disorder' as a description.[38][14]
## Entropy and Information theory
In information theory, entropy is the measure of the amount of information that is missing before reception and is sometimes referred to as Shannon entropy.[39] Shannon entropy is a broad and general concept which finds applications in information theory as well as thermodynamics. It was originally devised by Claude Shannon in 1948 to study the amount of information in a transmitted message. The definition of the information entropy is, however, quite general, and is expressed in terms of a discrete set of probabilities <math>p_i</math>. In the case of transmitted messages, these probabilities were the probabilities that a particular message was actually transmitted, and the entropy of the message system was a measure of how much information was in the message. For the case of equal probabilities (i.e. each message is equally probable), the Shannon entropy (in bits) is just the number of yes/no questions needed to determine the content of the message.
The question of the link between information entropy and thermodynamic entropy is a hotly debated topic. Some authors argue that there is a link between the two,[40][41][42] while others will argue that they have absolutely nothing to do with each other.[43]
The expressions for the two entropies are very similar. The information entropy H for equal probabilities <math>p_i=p</math> is:
where K is a constant which determines the units of entropy. For example, if the units are bits, then K=1/ln(2). The thermodynamic entropy S , from a statistical mechanical point of view was first expressed by Boltzmann:
where p is the probability of a system being in a particular microstate, given that it is in a particular macrostate, and k is Boltzmann's constant. It can be seen that one may think of the thermodynamic entropy as Boltzmann's constant, divided by ln(2), times the number of yes/no questions that must be asked in order to determine the microstate of the system, given that we know the macrostate. The link between thermodynamic and information entropy was developed in a series of papers by Edwin Jaynes beginning in 1957.[44]
The problem[citation needed] with linking thermodynamic entropy to information entropy is that in information entropy the entire body of thermodynamics which deals with the physical nature of entropy is missing. The second law of thermodynamics which governs the behavior of thermodynamic systems in equilibrium, and the first law which expresses heat energy as the product of temperature and entropy are physical concepts rather than informational concepts. If thermodynamic entropy is seen as including all of the physical dynamics of entropy as well as the equilibrium statistical aspects, then information entropy gives only part of the description of thermodynamic entropy. Some authors, like Tom Schneider, argue for dropping the word entropy for the H function of information theory and using Shannon's other term "uncertainty" instead.[45]
## Ice melting example
The illustration for this article is a classic example in which entropy increases in a small 'universe', a thermodynamic system consisting of the 'surroundings' (the warm room) and 'system' (glass, ice, cold water). In this universe, some heat energy δQ from the warmer room surroundings (at 298 K or 25 °C) will spread out to the cooler system of ice and water at its constant temperature T of 273 K (0 °C), the melting temperature of ice. The entropy of the system will change by the amount dS = δQ/T, in this example δQ/273 K. (The heat δQ for this process is the energy required to change water from the solid state to the liquid state, and is called the enthalpy of fusion, i.e. the ΔH for ice fusion.) The entropy of the surroundings will change by an amount dS = −δQ/298 K. So in this example, the entropy of the system increases, whereas the entropy of the surroundings decreases.
It is important to realize that the decrease in the entropy of the surrounding room is less than the increase in the entropy of the ice and water: the room temperature of 298 K is larger than 273 K and therefore the ratio, (entropy change), of δQ/298 K for the surroundings is smaller than the ratio (entropy change), of δQ/273 K for the ice+water system. To find the entropy change of our "universe", we add up the entropy changes for its constituents: the surrounding room, and the ice+water. The total entropy change is positive; this is always true in spontaneous events in a thermodynamic system and it shows the predictive importance of entropy: the final net entropy after such an event is always greater than was the initial entropy.
As the temperature of the cool water rises to that of the room and the room further cools imperceptibly, the sum of the δQ/T over the continuous range, at many increments, in the initially cool to finally warm water can be found by calculus. The entire miniature "universe", i.e. this thermodynamic system, has increased in entropy. Energy has spontaneously become more dispersed and spread out in that "universe" than when the glass of ice water was introduced and became a "system" within it.
# Topics in entropy
## Entropy and life
For over a century and a half, beginning with Clausius' 1863 memoir "On the Concentration of Rays of Heat and Light, and on the Limits of its Action", much writing and research has been devoted to the relationship between thermodynamic entropy and the evolution of life. The argument that life feeds on negative entropy or negentropy as put forth in the 1944 book What is Life? by physicist Erwin Schrödinger served as a further stimulus to this research. Recent writings[citation needed] have utilized the concept of Gibbs free energy to elaborate on this issue. Tangentially, some creationists have argued that entropy rules out evolution.[46]
In the popular 1982 textbook Principles of Biochemistry by noted American biochemist Albert Lehninger, for example, it is argued that the order produced within cells as they grow and divide is more than compensated for by the disorder they create in their surroundings in the course of growth and division. In short, according to Lehninger, "living organisms preserve their internal order by taking from their surroundings free energy, in the form of nutrients or sunlight, and returning to their surroundings an equal amount of energy as heat and entropy."[47]
Evolution related definitions:
- Negentropy - a shorthand colloquial phrase for negative entropy.[48]
- Ectropy - a measure of the tendency of a dynamical system to do useful work and grow more organized.[31]
- Syntropy - a tendency towards order and symmetrical combinations and designs of ever more advantageous and orderly patterns.
- Extropy – a metaphorical term defining the extent of a living or organizational system's intelligence, functional order, vitality, energy, life, experience, and capacity and drive for improvement and growth.
- Ecological entropy - a measure of biodiversity in the study of biological ecology.
## The arrow of time
Entropy is the only quantity in the physical sciences that "picks" a particular direction for time, sometimes called an arrow of time. As we go "forward" in time, the Second Law of Thermodynamics tells us that the entropy of an isolated system can only increase or remain the same; it cannot decrease. Hence, from one perspective, entropy measurement is thought of as a kind of clock.
## Entropy and cosmology
As a finite universe may be considered an isolated system, it may be subject to the Second Law of Thermodynamics, so that its total entropy is constantly increasing. It has been speculated that the universe is fated to a heat death in which all the energy ends up as a homogeneous distribution of thermal energy, so that no more work can be extracted from any source.
If the universe can be considered to have generally increasing entropy, then - as Roger Penrose has pointed out - gravity plays an important role in the increase because gravity causes dispersed matter to accumulate into stars, which collapse eventually into black holes. Jacob Bekenstein and Stephen Hawking have shown that black holes have the maximum possible entropy of any object of equal size. This makes them likely end points of all entropy-increasing processes, if they are totally effective matter and energy traps. Hawking has, however, recently changed his stance on this aspect.
The role of entropy in cosmology remains a controversial subject. Recent work has cast extensive doubt on the heat death hypothesis and the applicability of any simple thermodynamic model to the universe in general. Although entropy does increase in the model of an expanding universe, the maximum possible entropy rises much more rapidly - thus entropy density is decreasing with time. This results in an "entropy gap" pushing the system further away from equilibrium. Other complicating factors, such as the energy density of the vacuum and macroscopic quantum effects, are difficult to reconcile with thermodynamical models, making any predictions of large-scale thermodynamics extremely difficult.
## Miscellaneous definitions
- Entropy unit - a non-S.I. unit of thermodynamic entropy, usually denoted "e.u." and equal to one calorie per kelvin
- Gibbs entropy - the usual statistical mechanical entropy of a thermodynamic system.
- Boltzmann entropy - a type of Gibbs entropy, which neglects internal statistical correlations in the overall particle distribution.
- Tsallis entropy - a generalization of the standard Boltzmann-Gibbs entropy.
- Standard molar entropy - is the entropy content of one mole of substance, under conditions of standard temperature and pressure.
- Black hole entropy - is the entropy carried by a black hole, which is proportional to the surface area of the black hole's event horizon.[49]
- Residual entropy - the entropy present after a substance is cooled arbitrarily close to absolute zero.
- Entropy of mixing - the change in the entropy when two different chemical substances or components are mixed.
- Loop entropy - is the entropy lost upon bringing together two residues of a polymer within a prescribed distance.
- Conformational entropy - is the entropy associated with the physical arrangement of a polymer chain that assumes a compact or globular state in solution.
- Entropic force - a microscopic force or reaction tendency related to system organization changes, molecular frictional considerations, and statistical variations.
- Free entropy - an entropic thermodynamic potential analogous to the free energy.
- Entropic explosion – an explosion in which the reactants undergo a large change in volume without releasing a large amount of heat.
- Entropy change – a change in entropy dS between two equilibrium states is given by the heat transferred dQrev divided by the absolute temperature T of the system in this interval.[50]
- Sackur-Tetrode entropy - the entropy of a monatomic classical ideal gas determined via quantum considerations.
# Other relations
## Other mathematical definitions
- Kolmogorov-Sinai entropy - a mathematical type of entropy in dynamical systems related to measures of partitions.
- Topological entropy - a way of defining entropy in an iterated function map in ergodic theory.
- Relative entropy - is a natural distance measure from a "true" probability distribution P to an arbitrary probability distribution Q.
- Rényi entropy - a generalized entropy measure for fractal systems.
## Sociological definitions
The concept of entropy has also entered the domain of sociology, generally as a metaphor for chaos, disorder or dissipation of energy, rather than as a direct measure of thermodynamic or information entropy:
- Entropology – the study or discussion of entropy or the name sometimes given to thermodynamics without differential equations.[5][51]
- Psychological entropy - the distribution of energy in the psyche, which tends to seek equilibrium or balance among all the structures of the psyche.[52]
- Economic entropy – a semi-quantitative measure of the irrevocable dissipation and degradation of natural materials and available energy with respect to economic activity.[53][54]
- Social entropy – a measure of social system structure, having both theoretical and statistical interpretations, i.e. society (macrosocietal variables) measured in terms of how the individual functions in society (microsocietal variables); also related to social equilibrium.[55]
- Corporate entropy - energy waste as red tape and business team inefficiency, i.e. energy lost to waste.[56] (This definition is comparable to von Clausewitz's concept of friction in war.)
# Quotes | https://www.wikidoc.org/index.php/Boltzmann_principle | |
99be532a5e4cfdb333f78097357b9c1e9adec424 | wikidoc | Boredom | Boredom
Boredom is an emotional state experienced during periods of lack of activities or when an individual is uninterested in the activities surrounding them.
# Etymology
The first record of the word boredom is in the novel Bleak House, by Charles Dickens, written in 1852, although the expression to be a bore had been used in the sense of "to be tiresome or dull" since 1768.
# Psychology
Boredom has been defined by Fisher in terms of its central psychological processes: “an unpleasant, transient affective state in which the individual feels a pervasive lack of interest in and difficulty concentrating on the current activity.” M. R. Leary and others define boredom similarly, and somewhat more succinctly, as “an affective experience associated with cognitive attentional processes.” These definitions make it clear that boredom arises not for a lack of things to do but the inability to latch onto any specific activity. Nothing engages us, despite an often profound desire for engagement.
There appear to be three general types of boredom, all of which involve problems of engagement of attention. These include times when we are prevented from engaging in something, when we are forced to engage in some unwanted activity, or when we are simply unable, for no apparent reason, to maintain engagement in any activity or spectacle.
An important psychological construct is that of boredom proneness; a tendency to experience boredom of all types. This is typically assessed by the Boredom Proneness Scale. Consistent with the definition provided above, recent research has found that boredom proneness is clearly and consistently associated with failures of attention. Boredom and boredom proneness are both theoretically and empirically linked to depression and depressive symptoms. Nonetheless, boredom proneness has been found to be as strongly correlated with attentional lapses as with depression.
Although boredom is often viewed as a trivial and mild irritant, boredom, and especially boredom proneness has been linked to an amazingly diverse range of psychological, physical, educational, and social problems.
# Philosophy
Boredom is a condition characterized by perception of one's environment as dull, tedious, and lacking in stimulation. This can result from leisure and a lack of aesthetic interests. Labor, however, and even art may be alienated and passive, or immersed in tedium (see Marx's theory of alienation). There is an inherent anxiety in boredom; people will expend considerable effort to prevent or remedy it, yet in many circumstances, it is accepted as suffering to be endured. Common passive ways to escape boredom are to sleep or to think creative thoughts (daydream). Typical active solutions consist in an intentional activity of some sort, often something new, as familiarity and repetition lead to the tedious.
Boredom also plays a role in existentialist thought. In contexts where one is confined, spatially or otherwise, boredom may be met with various religious activities, not because religion would want to associate itself with tedium, but rather, partly because boredom may be taken as the essential human condition, to which God, wisdom, or morality are the ultimate answers. Boredom is in fact taken in this sense by virtually all existentialist philosophers as well as by Schopenhauer. Heidegger wrote about boredom in two texts available in English, in the 1929/30 semester lecture course The Fundamental Concepts of Metaphysics, and again in the essay What is Metaphysics? published in the same year. In the lecture, Heidegger included about 100 pages on boredom, probably the most extensive philosophical treatment ever of the subject. He focused on waiting at train stations in particular as a major context of boredom. In Kierkegaard's remark in Either/Or, that "patience cannot be depicted" visually, there is a sense that any immediate moment of life may be fundamentally tedious.
Without stimulus or focus, the individual is confronted with nothingness, the meaninglessness of existence, and experiences existential anxiety. Heidegger states this idea nicely: "Profound boredom, drifting here and there in the abysses of our existence like a muffling fog, removes all things and men and oneself along with it into a remarkable indifference. This boredom reveals being as a whole."
Arthur Schopenhauer used the existence of boredom in an attempt to prove the vanity of human existence, stating, "...for if life, in the desire for which our essence and existence consists, possessed in itself a positive value and real content, there would be no such thing as boredom: mere existence would fulfil and satisfy us."
Erich Fromm and other similar thinkers of critical theory speak of bourgeois society in terms similar to boredom, and Fromm mentions sex and the automobile as fundamental outlets of postmodern boredom.
Above and beyond taste and character, the universal case of boredom consists in any instance of waiting, as Heidegger noted, such as in line, for someone else to arrive or finish a task, or while one is travelling.
Boredom, however, may also increase as travel becomes more convenient, as the vehicle may become more like the windowless monad in Leibniz's monadology. The automobile requires fast reflexes, making its operator busy and hence, perhaps for other reasons as well, making the ride more tedious despite being over sooner.
# Causes and effects
Although it has not been widely studied, research on boredom suggests that boredom is a major factor impacting diverse areas of a person's life. People ranked low on a boredom-proneness scale were found to have better performance in a wide variety of aspects of their lives, including career, education, and autonomy.
Boredom can be a symptom of clinical depression. Boredom can be a form of learned helplessness, a phenomenon closely related to depression. Some philosophies of parenting propose that if children are raised in an environment devoid of stimuli, and are not allowed or encouraged to interact with their environment, they will fail to develop the mental capacities to do so.
In a learning environment, a common cause of boredom is lack of understanding; for instance, if one is not following or connecting to the material in a class or lecture, it will usually seem boring. However, the opposite can also be true; something that is too easily understood, simple or transparent, can also be boring. Boredom is often inversely related to learning, and in school it may be a sign that a student is not challenged enough (or too challenged). An activity that is predictable to the students is likely to bore them.
Boredom has been studied as being related to drug abuse among teens.
Boredom has been proposed as a cause of pathological gambling behavior. A study found results consistent with the hypothesis that pathological gamblers seek stimulation to avoid states of boredom and depression.
# Popular culture and the arts
In Chapter 18 of the novel The Picture of Dorian Gray by Oscar Wilde (1854–1900) it is written; "The only horrible thing in the world is ennui, Dorian. That is the one sin for which there is no forgiveness".
Iggy Pop, the Deftones, Buzzcocks, and Blink-182 have all written songs with boredom mentioned in the title. Other songs about boredom and activities people turn to when bored include Green Day's song "Longview", System of a Down's "Lonely Day", and Bloodhound Gang's "Mope".
Douglas Adams depicted a robot named Marvin the Paranoid Android whose boredom appeared to be the defining trait of his existence in The Hitchhiker's Guide to the Galaxy. | Boredom
Template:Pp-semi-protected
Template:Redirect4
Template:Emotion
Boredom is an emotional state experienced during periods of lack of activities or when an individual is uninterested in the activities surrounding them.
# Etymology
The first record of the word boredom is in the novel Bleak House, by Charles Dickens, written in 1852,[1] although the expression to be a bore had been used in the sense of "to be tiresome or dull" since 1768.[2]
# Psychology
Boredom has been defined by Fisher in terms of its central psychological processes: “an unpleasant, transient affective state in which the individual feels a pervasive lack of interest in and difficulty concentrating on the current activity.”[3] M. R. Leary and others define boredom similarly, and somewhat more succinctly, as “an affective experience associated with cognitive attentional processes.”[4] These definitions make it clear that boredom arises not for a lack of things to do but the inability to latch onto any specific activity. Nothing engages us, despite an often profound desire for engagement.
There appear to be three general types of boredom, all of which involve problems of engagement of attention. These include times when we are prevented from engaging in something, when we are forced to engage in some unwanted activity, or when we are simply unable, for no apparent reason, to maintain engagement in any activity or spectacle.[5]
An important psychological construct is that of boredom proneness; a tendency to experience boredom of all types. This is typically assessed by the Boredom Proneness Scale.[6] Consistent with the definition provided above, recent research has found that boredom proneness is clearly and consistently associated with failures of attention.[7] Boredom and boredom proneness are both theoretically and empirically linked to depression and depressive symptoms.[8][9][10] Nonetheless, boredom proneness has been found to be as strongly correlated with attentional lapses as with depression.[11]
Although boredom is often viewed as a trivial and mild irritant, boredom, and especially boredom proneness has been linked to an amazingly diverse range of psychological, physical, educational, and social problems.
# Philosophy
Boredom is a condition characterized by perception of one's environment as dull, tedious, and lacking in stimulation. This can result from leisure and a lack of aesthetic interests. Labor, however, and even art may be alienated and passive, or immersed in tedium (see Marx's theory of alienation). There is an inherent anxiety in boredom; people will expend considerable effort to prevent or remedy it, yet in many circumstances, it is accepted as suffering to be endured. Common passive ways to escape boredom are to sleep or to think creative thoughts (daydream). Typical active solutions consist in an intentional activity of some sort, often something new, as familiarity and repetition lead to the tedious.
Boredom also plays a role in existentialist thought. In contexts where one is confined, spatially or otherwise, boredom may be met with various religious activities, not because religion would want to associate itself with tedium, but rather, partly because boredom may be taken as the essential human condition, to which God, wisdom, or morality are the ultimate answers. Boredom is in fact taken in this sense by virtually all existentialist philosophers as well as by Schopenhauer. Heidegger wrote about boredom in two texts available in English, in the 1929/30 semester lecture course The Fundamental Concepts of Metaphysics, and again in the essay What is Metaphysics? published in the same year. In the lecture, Heidegger included about 100 pages on boredom, probably the most extensive philosophical treatment ever of the subject. He focused on waiting at train stations in particular as a major context of boredom.[12] In Kierkegaard's remark in Either/Or, that "patience cannot be depicted" visually, there is a sense that any immediate moment of life may be fundamentally tedious.
Without stimulus or focus, the individual is confronted with nothingness, the meaninglessness of existence, and experiences existential anxiety. Heidegger states this idea nicely: "Profound boredom, drifting here and there in the abysses of our existence like a muffling fog, removes all things and men and oneself along with it into a remarkable indifference. This boredom reveals being as a whole."[13]
Arthur Schopenhauer used the existence of boredom in an attempt to prove the vanity of human existence, stating, "...for if life, in the desire for which our essence and existence consists, possessed in itself a positive value and real content, there would be no such thing as boredom: mere existence would fulfil and satisfy us."[14]
Erich Fromm and other similar thinkers of critical theory speak of bourgeois society in terms similar to boredom, and Fromm mentions sex and the automobile as fundamental outlets of postmodern boredom.
Above and beyond taste and character, the universal case of boredom consists in any instance of waiting, as Heidegger noted, such as in line, for someone else to arrive or finish a task, or while one is travelling.
Boredom, however, may also increase as travel becomes more convenient, as the vehicle may become more like the windowless monad in Leibniz's monadology. The automobile requires fast reflexes, making its operator busy and hence, perhaps for other reasons as well, making the ride more tedious despite being over sooner.
# Causes and effects
Although it has not been widely studied, research on boredom suggests that boredom is a major factor impacting diverse areas of a person's life. People ranked low on a boredom-proneness scale were found to have better performance in a wide variety of aspects of their lives, including career, education, and autonomy.[15]
Boredom can be a symptom of clinical depression. Boredom can be a form of learned helplessness, a phenomenon closely related to depression. Some philosophies of parenting propose that if children are raised in an environment devoid of stimuli, and are not allowed or encouraged to interact with their environment, they will fail to develop the mental capacities to do so.
In a learning environment, a common cause of boredom is lack of understanding; for instance, if one is not following or connecting to the material in a class or lecture, it will usually seem boring. However, the opposite can also be true; something that is too easily understood, simple or transparent, can also be boring. Boredom is often inversely related to learning, and in school it may be a sign that a student is not challenged enough (or too challenged). An activity that is predictable to the students is likely to bore them. [16]
Boredom has been studied as being related to drug abuse among teens. [17]
Boredom has been proposed as a cause of pathological gambling behavior. A study found results consistent with the hypothesis that pathological gamblers seek stimulation to avoid states of boredom and depression.[18]
# Popular culture and the arts
In Chapter 18 of the novel The Picture of Dorian Gray by Oscar Wilde (1854–1900) it is written; "The only horrible thing in the world is ennui, Dorian. That is the one sin for which there is no forgiveness".
Iggy Pop, the Deftones, Buzzcocks, and Blink-182 have all written songs with boredom mentioned in the title. Other songs about boredom and activities people turn to when bored include Green Day's song "Longview", System of a Down's "Lonely Day", and Bloodhound Gang's "Mope".
Douglas Adams depicted a robot named Marvin the Paranoid Android whose boredom appeared to be the defining trait of his existence in The Hitchhiker's Guide to the Galaxy. | https://www.wikidoc.org/index.php/Boredom | |
14aa961ebd625c563e4c3362cf335057d1e04d98 | wikidoc | Bovinae | Bovinae
The biological subfamily bovinae includes a diverse group of 10 genera of medium to large sized ungulates, including domestic cattle, the bison, the water buffalo, the yak, and the four-horned and spiral-horned antelopes. The evolutionary relationship between the members of the group is obscure, and their classification into loose tribes rather than formal sub-groups reflects this uncertainty. General characteristics include a cloven hoof and usually at least one of the sexes of a species having a true horn.
In most countries, bovines are used for food. Cows are eaten almost everywhere except in India, where bovines are considered sacred by Hindus.
# Systematics and classification
- FAMILY BOVIDAE
Subfamily Bovinae
Tribe Boselaphini
Genus Tetracerus
Four-horned Antelope, Tetracerus quadricornis
Genus Boselaphus
Nilgai or blue bull, Boselaphus tragocamelus (not to be confused with the extinct Bluebuck Hippotragus leucophaeus, Hippotraginae)
Tribe Bovini
Genus Bubalus
Domestic Asian Water buffalo, Bubalus bubalis
Wild Asian Water buffalo, Bubalus arnee
Lowland Anoa, Bubalus depressicornis
Mountain Anoa, Bubalus quarlesi
Tamaraw, Bubalus mindorensis
Genus Bos
Aurochs, Bos primigenius (extinct)
Banteng, Bos javanicus
Gaur, Bos gaurus
Gayal, Bos frontalis (domestic gaur)
Yak, Bos mutus
Domestic Cattle, Bos taurus (increasingly considered a subspecies of Bos primigenius)
Kouprey, Bos sauveli
Genus Pseudonovibos
Kting Voar, Pseudonovibos spiralis
Genus Pseudoryx
Saola, Pseudoryx nghetinhensis
Genus Syncerus
African Buffalo, Syncerus caffer
Genus Bison
American Bison, Bison bison
Wisent, Bison bonasus
Steppe Wisent, Bison priscus (extinct)
Tribe Strepsicerotini
Genus Tragelaphus (antelope-like)
Sitatunga, Tragelaphus spekeii
Nyala, Tragelaphus angasii
Bushbuck, Tragelaphus scriptus
Mountain Nyala Tragelaphus buxtoni
Lesser Kudu, Tragelaphus imberbis
Greater Kudu, Tragelaphus strepsiceros
Bongo, Tragelaphus eurycerus
Genus Taurotragus
Common Eland, Taurotragus oryx
Giant Eland, Taurotragus derbianus
- Subfamily Bovinae
Tribe Boselaphini
Genus Tetracerus
Four-horned Antelope, Tetracerus quadricornis
Genus Boselaphus
Nilgai or blue bull, Boselaphus tragocamelus (not to be confused with the extinct Bluebuck Hippotragus leucophaeus, Hippotraginae)
Tribe Bovini
Genus Bubalus
Domestic Asian Water buffalo, Bubalus bubalis
Wild Asian Water buffalo, Bubalus arnee
Lowland Anoa, Bubalus depressicornis
Mountain Anoa, Bubalus quarlesi
Tamaraw, Bubalus mindorensis
Genus Bos
Aurochs, Bos primigenius (extinct)
Banteng, Bos javanicus
Gaur, Bos gaurus
Gayal, Bos frontalis (domestic gaur)
Yak, Bos mutus
Domestic Cattle, Bos taurus (increasingly considered a subspecies of Bos primigenius)
Kouprey, Bos sauveli
Genus Pseudonovibos
Kting Voar, Pseudonovibos spiralis
Genus Pseudoryx
Saola, Pseudoryx nghetinhensis
Genus Syncerus
African Buffalo, Syncerus caffer
Genus Bison
American Bison, Bison bison
Wisent, Bison bonasus
Steppe Wisent, Bison priscus (extinct)
Tribe Strepsicerotini
Genus Tragelaphus (antelope-like)
Sitatunga, Tragelaphus spekeii
Nyala, Tragelaphus angasii
Bushbuck, Tragelaphus scriptus
Mountain Nyala Tragelaphus buxtoni
Lesser Kudu, Tragelaphus imberbis
Greater Kudu, Tragelaphus strepsiceros
Bongo, Tragelaphus eurycerus
Genus Taurotragus
Common Eland, Taurotragus oryx
Giant Eland, Taurotragus derbianus
- Tribe Boselaphini
Genus Tetracerus
Four-horned Antelope, Tetracerus quadricornis
Genus Boselaphus
Nilgai or blue bull, Boselaphus tragocamelus (not to be confused with the extinct Bluebuck Hippotragus leucophaeus, Hippotraginae)
- Genus Tetracerus
Four-horned Antelope, Tetracerus quadricornis
- Four-horned Antelope, Tetracerus quadricornis
- Genus Boselaphus
Nilgai or blue bull, Boselaphus tragocamelus (not to be confused with the extinct Bluebuck Hippotragus leucophaeus, Hippotraginae)
- Nilgai or blue bull, Boselaphus tragocamelus (not to be confused with the extinct Bluebuck Hippotragus leucophaeus, Hippotraginae)
- Tribe Bovini
Genus Bubalus
Domestic Asian Water buffalo, Bubalus bubalis
Wild Asian Water buffalo, Bubalus arnee
Lowland Anoa, Bubalus depressicornis
Mountain Anoa, Bubalus quarlesi
Tamaraw, Bubalus mindorensis
Genus Bos
Aurochs, Bos primigenius (extinct)
Banteng, Bos javanicus
Gaur, Bos gaurus
Gayal, Bos frontalis (domestic gaur)
Yak, Bos mutus
Domestic Cattle, Bos taurus (increasingly considered a subspecies of Bos primigenius)
Kouprey, Bos sauveli
Genus Pseudonovibos
Kting Voar, Pseudonovibos spiralis
Genus Pseudoryx
Saola, Pseudoryx nghetinhensis
Genus Syncerus
African Buffalo, Syncerus caffer
Genus Bison
American Bison, Bison bison
Wisent, Bison bonasus
Steppe Wisent, Bison priscus (extinct)
- Genus Bubalus
Domestic Asian Water buffalo, Bubalus bubalis
Wild Asian Water buffalo, Bubalus arnee
Lowland Anoa, Bubalus depressicornis
Mountain Anoa, Bubalus quarlesi
Tamaraw, Bubalus mindorensis
- Domestic Asian Water buffalo, Bubalus bubalis
- Wild Asian Water buffalo, Bubalus arnee
- Lowland Anoa, Bubalus depressicornis
- Mountain Anoa, Bubalus quarlesi
- Tamaraw, Bubalus mindorensis
- Genus Bos
Aurochs, Bos primigenius (extinct)
Banteng, Bos javanicus
Gaur, Bos gaurus
Gayal, Bos frontalis (domestic gaur)
Yak, Bos mutus
Domestic Cattle, Bos taurus (increasingly considered a subspecies of Bos primigenius)
Kouprey, Bos sauveli
- Aurochs, Bos primigenius (extinct)
- Banteng, Bos javanicus
- Gaur, Bos gaurus
- Gayal, Bos frontalis (domestic gaur)
- Yak, Bos mutus
- Domestic Cattle, Bos taurus (increasingly considered a subspecies of Bos primigenius)
- Kouprey, Bos sauveli
- Genus Pseudonovibos
Kting Voar, Pseudonovibos spiralis
- Kting Voar, Pseudonovibos spiralis
- Genus Pseudoryx
Saola, Pseudoryx nghetinhensis
- Saola, Pseudoryx nghetinhensis
- Genus Syncerus
African Buffalo, Syncerus caffer
- African Buffalo, Syncerus caffer
- Genus Bison
American Bison, Bison bison
Wisent, Bison bonasus
Steppe Wisent, Bison priscus (extinct)
- American Bison, Bison bison
- Wisent, Bison bonasus
- Steppe Wisent, Bison priscus (extinct)
- Tribe Strepsicerotini
Genus Tragelaphus (antelope-like)
Sitatunga, Tragelaphus spekeii
Nyala, Tragelaphus angasii
Bushbuck, Tragelaphus scriptus
Mountain Nyala Tragelaphus buxtoni
Lesser Kudu, Tragelaphus imberbis
Greater Kudu, Tragelaphus strepsiceros
Bongo, Tragelaphus eurycerus
Genus Taurotragus
Common Eland, Taurotragus oryx
Giant Eland, Taurotragus derbianus
- Genus Tragelaphus (antelope-like)
Sitatunga, Tragelaphus spekeii
Nyala, Tragelaphus angasii
Bushbuck, Tragelaphus scriptus
Mountain Nyala Tragelaphus buxtoni
Lesser Kudu, Tragelaphus imberbis
Greater Kudu, Tragelaphus strepsiceros
Bongo, Tragelaphus eurycerus
- Sitatunga, Tragelaphus spekeii
- Nyala, Tragelaphus angasii
- Bushbuck, Tragelaphus scriptus
- Mountain Nyala Tragelaphus buxtoni
- Lesser Kudu, Tragelaphus imberbis
- Greater Kudu, Tragelaphus strepsiceros
- Bongo, Tragelaphus eurycerus
- Genus Taurotragus
Common Eland, Taurotragus oryx
Giant Eland, Taurotragus derbianus
- Common Eland, Taurotragus oryx
- Giant Eland, Taurotragus derbianus
# Etymology
Bovine is derived from Latin bos, "ox", through Late Latin bovinus.Bos derives from the Greek word Βους (Vus)meaning ox. | Bovinae
The biological subfamily bovinae includes a diverse group of 10 genera of medium to large sized ungulates, including domestic cattle, the bison, the water buffalo, the yak, and the four-horned and spiral-horned antelopes. The evolutionary relationship between the members of the group is obscure, and their classification into loose tribes rather than formal sub-groups reflects this uncertainty. General characteristics include a cloven hoof and usually at least one of the sexes of a species having a true horn.
In most countries, bovines are used for food. Cows are eaten almost everywhere except in India, where bovines are considered sacred by Hindus.
# Systematics and classification
- FAMILY BOVIDAE
Subfamily Bovinae
Tribe Boselaphini
Genus Tetracerus
Four-horned Antelope, Tetracerus quadricornis
Genus Boselaphus
Nilgai or blue bull, Boselaphus tragocamelus (not to be confused with the extinct Bluebuck Hippotragus leucophaeus, Hippotraginae)
Tribe Bovini
Genus Bubalus
Domestic Asian Water buffalo, Bubalus bubalis
Wild Asian Water buffalo, Bubalus arnee
Lowland Anoa, Bubalus depressicornis
Mountain Anoa, Bubalus quarlesi
Tamaraw, Bubalus mindorensis
Genus Bos
Aurochs, Bos primigenius (extinct)
Banteng, Bos javanicus
Gaur, Bos gaurus
Gayal, Bos frontalis (domestic gaur)
Yak, Bos mutus
Domestic Cattle, Bos taurus (increasingly considered a subspecies of Bos primigenius)
Kouprey, Bos sauveli
Genus Pseudonovibos
Kting Voar, Pseudonovibos spiralis
Genus Pseudoryx
Saola, Pseudoryx nghetinhensis
Genus Syncerus
African Buffalo, Syncerus caffer
Genus Bison
American Bison, Bison bison
Wisent, Bison bonasus
Steppe Wisent, Bison priscus (extinct)
Tribe Strepsicerotini
Genus Tragelaphus (antelope-like)
Sitatunga, Tragelaphus spekeii
Nyala, Tragelaphus angasii
Bushbuck, Tragelaphus scriptus
Mountain Nyala Tragelaphus buxtoni
Lesser Kudu, Tragelaphus imberbis
Greater Kudu, Tragelaphus strepsiceros
Bongo, Tragelaphus eurycerus
Genus Taurotragus
Common Eland, Taurotragus oryx
Giant Eland, Taurotragus derbianus
- Subfamily Bovinae
Tribe Boselaphini
Genus Tetracerus
Four-horned Antelope, Tetracerus quadricornis
Genus Boselaphus
Nilgai or blue bull, Boselaphus tragocamelus (not to be confused with the extinct Bluebuck Hippotragus leucophaeus, Hippotraginae)
Tribe Bovini
Genus Bubalus
Domestic Asian Water buffalo, Bubalus bubalis
Wild Asian Water buffalo, Bubalus arnee
Lowland Anoa, Bubalus depressicornis
Mountain Anoa, Bubalus quarlesi
Tamaraw, Bubalus mindorensis
Genus Bos
Aurochs, Bos primigenius (extinct)
Banteng, Bos javanicus
Gaur, Bos gaurus
Gayal, Bos frontalis (domestic gaur)
Yak, Bos mutus
Domestic Cattle, Bos taurus (increasingly considered a subspecies of Bos primigenius)
Kouprey, Bos sauveli
Genus Pseudonovibos
Kting Voar, Pseudonovibos spiralis
Genus Pseudoryx
Saola, Pseudoryx nghetinhensis
Genus Syncerus
African Buffalo, Syncerus caffer
Genus Bison
American Bison, Bison bison
Wisent, Bison bonasus
Steppe Wisent, Bison priscus (extinct)
Tribe Strepsicerotini
Genus Tragelaphus (antelope-like)
Sitatunga, Tragelaphus spekeii
Nyala, Tragelaphus angasii
Bushbuck, Tragelaphus scriptus
Mountain Nyala Tragelaphus buxtoni
Lesser Kudu, Tragelaphus imberbis
Greater Kudu, Tragelaphus strepsiceros
Bongo, Tragelaphus eurycerus
Genus Taurotragus
Common Eland, Taurotragus oryx
Giant Eland, Taurotragus derbianus
- Tribe Boselaphini
Genus Tetracerus
Four-horned Antelope, Tetracerus quadricornis
Genus Boselaphus
Nilgai or blue bull, Boselaphus tragocamelus (not to be confused with the extinct Bluebuck Hippotragus leucophaeus, Hippotraginae)
- Genus Tetracerus
Four-horned Antelope, Tetracerus quadricornis
- Four-horned Antelope, Tetracerus quadricornis
- Genus Boselaphus
Nilgai or blue bull, Boselaphus tragocamelus (not to be confused with the extinct Bluebuck Hippotragus leucophaeus, Hippotraginae)
- Nilgai or blue bull, Boselaphus tragocamelus (not to be confused with the extinct Bluebuck Hippotragus leucophaeus, Hippotraginae)
- Tribe Bovini
Genus Bubalus
Domestic Asian Water buffalo, Bubalus bubalis
Wild Asian Water buffalo, Bubalus arnee
Lowland Anoa, Bubalus depressicornis
Mountain Anoa, Bubalus quarlesi
Tamaraw, Bubalus mindorensis
Genus Bos
Aurochs, Bos primigenius (extinct)
Banteng, Bos javanicus
Gaur, Bos gaurus
Gayal, Bos frontalis (domestic gaur)
Yak, Bos mutus
Domestic Cattle, Bos taurus (increasingly considered a subspecies of Bos primigenius)
Kouprey, Bos sauveli
Genus Pseudonovibos
Kting Voar, Pseudonovibos spiralis
Genus Pseudoryx
Saola, Pseudoryx nghetinhensis
Genus Syncerus
African Buffalo, Syncerus caffer
Genus Bison
American Bison, Bison bison
Wisent, Bison bonasus
Steppe Wisent, Bison priscus (extinct)
- Genus Bubalus
Domestic Asian Water buffalo, Bubalus bubalis
Wild Asian Water buffalo, Bubalus arnee
Lowland Anoa, Bubalus depressicornis
Mountain Anoa, Bubalus quarlesi
Tamaraw, Bubalus mindorensis
- Domestic Asian Water buffalo, Bubalus bubalis
- Wild Asian Water buffalo, Bubalus arnee
- Lowland Anoa, Bubalus depressicornis
- Mountain Anoa, Bubalus quarlesi
- Tamaraw, Bubalus mindorensis
- Genus Bos
Aurochs, Bos primigenius (extinct)
Banteng, Bos javanicus
Gaur, Bos gaurus
Gayal, Bos frontalis (domestic gaur)
Yak, Bos mutus
Domestic Cattle, Bos taurus (increasingly considered a subspecies of Bos primigenius)
Kouprey, Bos sauveli
- Aurochs, Bos primigenius (extinct)
- Banteng, Bos javanicus
- Gaur, Bos gaurus
- Gayal, Bos frontalis (domestic gaur)
- Yak, Bos mutus
- Domestic Cattle, Bos taurus (increasingly considered a subspecies of Bos primigenius)
- Kouprey, Bos sauveli
- Genus Pseudonovibos
Kting Voar, Pseudonovibos spiralis
- Kting Voar, Pseudonovibos spiralis
- Genus Pseudoryx
Saola, Pseudoryx nghetinhensis
- Saola, Pseudoryx nghetinhensis
- Genus Syncerus
African Buffalo, Syncerus caffer
- African Buffalo, Syncerus caffer
- Genus Bison
American Bison, Bison bison
Wisent, Bison bonasus
Steppe Wisent, Bison priscus (extinct)
- American Bison, Bison bison
- Wisent, Bison bonasus
- Steppe Wisent, Bison priscus (extinct)
- Tribe Strepsicerotini
Genus Tragelaphus (antelope-like)
Sitatunga, Tragelaphus spekeii
Nyala, Tragelaphus angasii
Bushbuck, Tragelaphus scriptus
Mountain Nyala Tragelaphus buxtoni
Lesser Kudu, Tragelaphus imberbis
Greater Kudu, Tragelaphus strepsiceros
Bongo, Tragelaphus eurycerus
Genus Taurotragus
Common Eland, Taurotragus oryx
Giant Eland, Taurotragus derbianus
- Genus Tragelaphus (antelope-like)
Sitatunga, Tragelaphus spekeii
Nyala, Tragelaphus angasii
Bushbuck, Tragelaphus scriptus
Mountain Nyala Tragelaphus buxtoni
Lesser Kudu, Tragelaphus imberbis
Greater Kudu, Tragelaphus strepsiceros
Bongo, Tragelaphus eurycerus
- Sitatunga, Tragelaphus spekeii
- Nyala, Tragelaphus angasii
- Bushbuck, Tragelaphus scriptus
- Mountain Nyala Tragelaphus buxtoni
- Lesser Kudu, Tragelaphus imberbis
- Greater Kudu, Tragelaphus strepsiceros
- Bongo, Tragelaphus eurycerus
- Genus Taurotragus
Common Eland, Taurotragus oryx
Giant Eland, Taurotragus derbianus
- Common Eland, Taurotragus oryx
- Giant Eland, Taurotragus derbianus
# Etymology
Bovine is derived from Latin bos, "ox", through Late Latin bovinus.Bos derives from the Greek word Βους (Vus)meaning ox. | https://www.wikidoc.org/index.php/Bovinae | |
7d3488dafc7ae73621b64dc91a99ee2e1a7fe398 | wikidoc | Fistula | Fistula
# Overview
In medicine, a fistula (pl. fistulas or fistulae) is an abnormal connection or passageway between two epithelium-lined organs or vessels that normally do not connect.
# Location of fistulas
Fistulas can develop in various parts of the body. The following list is sorted by the International Statistical Classification of Diseases and Related Health Problems.
## H: Diseases of the eye, adnexa, ear, and mastoid process
- (H04.6) Lacrimal fistula
- (H70.1) Mastoid fistula
Craniosinus fistula: between the intracranial space and a paranasal sinus
- Craniosinus fistula: between the intracranial space and a paranasal sinus
- (H83.1) Labyrinthine fistula
Perilymph fistula: tear between the membranes between the middle and inner ears
- Perilymph fistula: tear between the membranes between the middle and inner ears
## I: Diseases of the circulatory system
- (I25.4) Coronary arteriovenous fistula, acquired
- (I28.0) Arteriovenous fistula of pulmonary vessels
Pulmonary arteriovenous fistula: between an artery and vein of the lungs, resulting in shunting of blood. This results in improperly oxygenated blood.
- Pulmonary arteriovenous fistula: between an artery and vein of the lungs, resulting in shunting of blood. This results in improperly oxygenated blood.
- (I67.1) Cerebral arteriovenous fistula, acquired
- (I77.0) Arteriovenous fistula, acquired
- (I77.2) Fistula of artery
## J: Diseases of the respiratory system
- (J86.0) Pyothorax with fistula
- (J95.0) Tracheoesophageal fistula following tracheostomy: between the breathing and the feeding tubes
## K: Diseases of the digestive system
- (K11.4) Fistula of salivary gland
- (K31.6) Fistula of stomach and duodenum
- (K31.6) Gastrocolic fistula
- (K31.6) Gastrojejunocolic fistula
Enterocutaneous fistula: between the intestine and the skin surface, namely from the duodenum or the jejunum or the ileum. This definition excludes the fistulas arising from the colon or the appendix.
Gastric fistula: from the stomach to the skin surface
- Enterocutaneous fistula: between the intestine and the skin surface, namely from the duodenum or the jejunum or the ileum. This definition excludes the fistulas arising from the colon or the appendix.
- Gastric fistula: from the stomach to the skin surface
- (K38.3) Fistula of appendix
- (K60.3) Anal fistula
(K60.3) Anorectal fistula: connecting the rectum or other anorectal area to the skin surface. This results in abnormal discharge of feces through an opening other than the anus. Also called fistula-in-ano.
Fecal fistula: see Anorectal
Fistula-in-ano: see Anorectal
- (K60.3) Anorectal fistula: connecting the rectum or other anorectal area to the skin surface. This results in abnormal discharge of feces through an opening other than the anus. Also called fistula-in-ano.
Fecal fistula: see Anorectal
Fistula-in-ano: see Anorectal
- Fecal fistula: see Anorectal
- Fistula-in-ano: see Anorectal
- (K60.4) Rectal fistula
- (K60.5) Anorectal fistula
- (K63.2) Fistula of intestine
Enteroenteral fistula: between two parts of the intestine
- Enteroenteral fistula: between two parts of the intestine
- (K82.3) Fistula of gallbladder
- (K83.3) Fistula of bile duct
Biliary fistula: connecting the bile ducts to the skin surface, often caused by gallbladder surgery
Pancreatic fistula: between the pancreas and the exterior via the abdominal wall
- Biliary fistula: connecting the bile ducts to the skin surface, often caused by gallbladder surgery
- Pancreatic fistula: between the pancreas and the exterior via the abdominal wall
## M: Diseases of the musculoskeletal system and connective tissue
- (M25.1) Fistula of joint
## N: Diseases of the genitourinary system
- (N32.1) Vesicointestinal fistula
- (N36.0) Urethral fistula
Innora:between the prostatic utricle and the outside of the body
- Innora:between the prostatic utricle and the outside of the body
- (N64.0) Fistula of nipple
- (N82) Fistulae involving female genital tract / Obstetric fistula
(N82.0) Vesicovaginal fistula: between the bladder and the vagina
(N82.1) Other female urinary-genital tract fistulae
Cervical fistula: abnormal opening in the cervix
(N82.2) Fistula of vagina to small intestine
Enterovaginal fistula: between the intestine and the vagina
(N82.3) Fistula of vagina to large intestine
Rectovaginal: between the rectum and the vagina
(N82.4) Other female intestinal-genital tract fistulae
(N82.5) Female genital tract-skin fistulae
(N82.8) Other female genital tract fistulae
(N82.9) Female genital tract fistula, unspecified
- (N82.0) Vesicovaginal fistula: between the bladder and the vagina
- (N82.1) Other female urinary-genital tract fistulae
Cervical fistula: abnormal opening in the cervix
- Cervical fistula: abnormal opening in the cervix
- (N82.2) Fistula of vagina to small intestine
Enterovaginal fistula: between the intestine and the vagina
- Enterovaginal fistula: between the intestine and the vagina
- (N82.3) Fistula of vagina to large intestine
Rectovaginal: between the rectum and the vagina
- Rectovaginal: between the rectum and the vagina
- (N82.4) Other female intestinal-genital tract fistulae
- (N82.5) Female genital tract-skin fistulae
- (N82.8) Other female genital tract fistulae
- (N82.9) Female genital tract fistula, unspecified
## Q: Congenital malformations, deformations and chromosomal abnormalities
- (Q18.0) Sinus, fistula and cyst of branchial cleft
Congenital Preauricular fistula: A small pit in front of the ear. Also called Fistula Auris Congenita or Ear Pit.
- Congenital Preauricular fistula: A small pit in front of the ear. Also called Fistula Auris Congenita or Ear Pit.
- (Q26.6) Portal vein-hepatic artery fistula
- (Q38.0) Congenital fistula of lip
- (Q38.4) Congenital fistula of salivary gland
- (Q42.0) Congenital absence, atresia and stenosis of rectum with fistula
- (Q42.2) Congenital absence, atresia and stenosis of anus with fistula
- (Q43.6) Congenital fistula of rectum and anus
- (Q51.7) Congenital fistulae between uterus and digestive and urinary tracts
- (Q52.2) Congenital rectovaginal fistula
## T: External causes
- (T14.5) Traumatic arteriovenous fistula
- (T81.8) Persistent postoperative fistula
# Types of fistulas
Various types of fistulas include:
- Blind: with only one open end
- Complete: with both external and internal openings
- Incomplete: a fistula with an external skin opening, which does not connect to any internal organ
Although most fistulas are in forms of a tube, some can also have multiple branches.
# Causes
Various causes of fistula are:
- Diseases: Inflammatory bowel diseases, such as Crohn's disease and ulcerative colitis, are the leading causes of anorectal, enteroenteral, and enterocutaneous fistulas. A person with severe stage-3 hidradenitis suppurativa will also develop fistulas.
- Medical treatment: Complications from gallbladder surgery can lead to biliary fistula. Radiation therapy can lead to vesicovaginal fistula. An arteriovenous fistula can be deliberately created, as described below in therapeutic use.
- Trauma: Head trauma can lead to perilymph fistulas, whereas trauma to other parts of the body can cause arteriovenous fistulas. Obstructed labor can lead to vesicovaginal and rectovaginal fistulas. An obstetric fistula develops when blood supply to the tissues of the vagina and the bladder (and/or rectum) is cut off during prolonged obstructed labor. The tissues die and a hole forms through which urine and/or feces pass uncontrollably. Vesicovaginal and rectovaginal fistulas may also be caused by rape, in particular gang rape, and rape with foreign objects, as evidenced by the abnormally high number of women in conflict areas who have suffered fistulae.
- In 2003, thousands of women in eastern Congo presented themselves for treatment of traumatic fistula caused by systematic, violent gang rape that occurred during the country's five years of war. So many cases have been reported that the destruction of the vagina is considered a war injury and recorded by doctors as a crime of combat.
# Treatment
Treatment for fistulae varies depending on the cause and extent of the fistula, but often involves surgical intervention combined with antibiotic therapy.
Typically the first step in treating a fistula is an examination by a doctor to determine the extent and "path" that the fistula takes through the tissue.
In some cases the fistula is temporarily covered, for example a fistula caused by cleft palate is often treated with a palatal obturator to delay the need for surgery to a more appropriate age.
Surgery is often required to assure adequate drainage of the fistula (so that pus may escape without forming an abscess). Various surgical procedures are commonly used, most commonly fistulotomy, placement of a seton (a cord that is passed through the path of the fistula to keep it open for draining), or an endorectal flap procedure (where healthy tissue is pulled over the internal side of the fistula to keep feces or other material from reinfecting the channel). Treatments involving filling the fistula with fibrin glue or plugging it with plugs made of porcine small intestine submucosa have also been explored in recent years, with variable success. Surgery for anorectal fistulae is not without side effects, including recurrence, reinfection, and incontinence.
It is important to note that surgical treatment of a fistula without diagnosis or management of the underlying condition, if any, is not recommended. For example, surgical treatment of fistulae in Crohn's disease can be effective, but if the Crohn's disease itself is not treated, the rate of recurrence of fistula is very high (well above 50%).
# Therapeutic use
In end stage renal failure patients, a cimino fistula is often deliberately created in the arm by means of a short day surgery in order to permit easier withdrawal of blood for hemodialysis.
As a radical treatment for portal hypertension, surgical creation of a portacaval fistula produces an anastomosis between the hepatic portal vein and the inferior vena cava across the omental foramen (of Winslow). This spares the portal venous system from high pressure which can cause esophageal varices, caput madusae, and hemorrhoids. | Fistula
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
# Overview
Template:Search infobox
In medicine, a fistula (pl. fistulas or fistulae) is an abnormal connection or passageway between two epithelium-lined organs or vessels that normally do not connect.
# Location of fistulas
Fistulas can develop in various parts of the body. The following list is sorted by the International Statistical Classification of Diseases and Related Health Problems.
## H: Diseases of the eye, adnexa, ear, and mastoid process
- (H04.6) Lacrimal fistula
- (H70.1) Mastoid fistula
Craniosinus fistula: between the intracranial space and a paranasal sinus
- Craniosinus fistula: between the intracranial space and a paranasal sinus
- (H83.1) Labyrinthine fistula
Perilymph fistula: tear between the membranes between the middle and inner ears
- Perilymph fistula: tear between the membranes between the middle and inner ears
## I: Diseases of the circulatory system
- (I25.4) Coronary arteriovenous fistula, acquired
- (I28.0) Arteriovenous fistula of pulmonary vessels
Pulmonary arteriovenous fistula: between an artery and vein of the lungs, resulting in shunting of blood. This results in improperly oxygenated blood.
- Pulmonary arteriovenous fistula: between an artery and vein of the lungs, resulting in shunting of blood. This results in improperly oxygenated blood.
- (I67.1) Cerebral arteriovenous fistula, acquired
- (I77.0) Arteriovenous fistula, acquired
- (I77.2) Fistula of artery
## J: Diseases of the respiratory system
- (J86.0) Pyothorax with fistula
- (J95.0) Tracheoesophageal fistula following tracheostomy: between the breathing and the feeding tubes
## K: Diseases of the digestive system
- (K11.4) Fistula of salivary gland
- (K31.6) Fistula of stomach and duodenum
- (K31.6) Gastrocolic fistula
- (K31.6) Gastrojejunocolic fistula
Enterocutaneous fistula: between the intestine and the skin surface, namely from the duodenum or the jejunum or the ileum. This definition excludes the fistulas arising from the colon or the appendix.
Gastric fistula: from the stomach to the skin surface
- Enterocutaneous fistula: between the intestine and the skin surface, namely from the duodenum or the jejunum or the ileum. This definition excludes the fistulas arising from the colon or the appendix.
- Gastric fistula: from the stomach to the skin surface
- (K38.3) Fistula of appendix
- (K60.3) Anal fistula
(K60.3) Anorectal fistula: connecting the rectum or other anorectal area to the skin surface. This results in abnormal discharge of feces through an opening other than the anus. Also called fistula-in-ano.
Fecal fistula: see Anorectal
Fistula-in-ano: see Anorectal
- (K60.3) Anorectal fistula: connecting the rectum or other anorectal area to the skin surface. This results in abnormal discharge of feces through an opening other than the anus. Also called fistula-in-ano.
Fecal fistula: see Anorectal
Fistula-in-ano: see Anorectal
- Fecal fistula: see Anorectal
- Fistula-in-ano: see Anorectal
- (K60.4) Rectal fistula
- (K60.5) Anorectal fistula
- (K63.2) Fistula of intestine
Enteroenteral fistula: between two parts of the intestine
- Enteroenteral fistula: between two parts of the intestine
- (K82.3) Fistula of gallbladder
- (K83.3) Fistula of bile duct
Biliary fistula: connecting the bile ducts to the skin surface, often caused by gallbladder surgery
Pancreatic fistula: between the pancreas and the exterior via the abdominal wall
- Biliary fistula: connecting the bile ducts to the skin surface, often caused by gallbladder surgery
- Pancreatic fistula: between the pancreas and the exterior via the abdominal wall
## M: Diseases of the musculoskeletal system and connective tissue
- (M25.1) Fistula of joint
## N: Diseases of the genitourinary system
- (N32.1) Vesicointestinal fistula
- (N36.0) Urethral fistula
Innora:between the prostatic utricle and the outside of the body
- Innora:between the prostatic utricle and the outside of the body
- (N64.0) Fistula of nipple
- (N82) Fistulae involving female genital tract / Obstetric fistula
(N82.0) Vesicovaginal fistula: between the bladder and the vagina
(N82.1) Other female urinary-genital tract fistulae
Cervical fistula: abnormal opening in the cervix
(N82.2) Fistula of vagina to small intestine
Enterovaginal fistula: between the intestine and the vagina
(N82.3) Fistula of vagina to large intestine
Rectovaginal: between the rectum and the vagina
(N82.4) Other female intestinal-genital tract fistulae
(N82.5) Female genital tract-skin fistulae
(N82.8) Other female genital tract fistulae
(N82.9) Female genital tract fistula, unspecified
- (N82.0) Vesicovaginal fistula: between the bladder and the vagina
- (N82.1) Other female urinary-genital tract fistulae
Cervical fistula: abnormal opening in the cervix
- Cervical fistula: abnormal opening in the cervix
- (N82.2) Fistula of vagina to small intestine
Enterovaginal fistula: between the intestine and the vagina
- Enterovaginal fistula: between the intestine and the vagina
- (N82.3) Fistula of vagina to large intestine
Rectovaginal: between the rectum and the vagina
- Rectovaginal: between the rectum and the vagina
- (N82.4) Other female intestinal-genital tract fistulae
- (N82.5) Female genital tract-skin fistulae
- (N82.8) Other female genital tract fistulae
- (N82.9) Female genital tract fistula, unspecified
## Q: Congenital malformations, deformations and chromosomal abnormalities
- (Q18.0) Sinus, fistula and cyst of branchial cleft
Congenital Preauricular fistula: A small pit in front of the ear. Also called Fistula Auris Congenita or Ear Pit.
- Congenital Preauricular fistula: A small pit in front of the ear. Also called Fistula Auris Congenita or Ear Pit.
- (Q26.6) Portal vein-hepatic artery fistula
- (Q38.0) Congenital fistula of lip
- (Q38.4) Congenital fistula of salivary gland
- (Q42.0) Congenital absence, atresia and stenosis of rectum with fistula
- (Q42.2) Congenital absence, atresia and stenosis of anus with fistula
- (Q43.6) Congenital fistula of rectum and anus
- (Q51.7) Congenital fistulae between uterus and digestive and urinary tracts
- (Q52.2) Congenital rectovaginal fistula
## T: External causes
- (T14.5) Traumatic arteriovenous fistula
- (T81.8) Persistent postoperative fistula
# Types of fistulas
Various types of fistulas include:
- Blind: with only one open end
- Complete: with both external and internal openings
- Incomplete: a fistula with an external skin opening, which does not connect to any internal organ
Although most fistulas are in forms of a tube, some can also have multiple branches.
# Causes
Various causes of fistula are:
- Diseases: Inflammatory bowel diseases, such as Crohn's disease and ulcerative colitis, are the leading causes of anorectal, enteroenteral, and enterocutaneous fistulas. A person with severe stage-3 hidradenitis suppurativa will also develop fistulas.
- Medical treatment: Complications from gallbladder surgery can lead to biliary fistula. Radiation therapy can lead to vesicovaginal fistula. An arteriovenous fistula can be deliberately created, as described below in therapeutic use.
- Trauma: Head trauma can lead to perilymph fistulas, whereas trauma to other parts of the body can cause arteriovenous fistulas. Obstructed labor can lead to vesicovaginal and rectovaginal fistulas. An obstetric fistula develops when blood supply to the tissues of the vagina and the bladder (and/or rectum) is cut off during prolonged obstructed labor. The tissues die and a hole forms through which urine and/or feces pass uncontrollably. Vesicovaginal and rectovaginal fistulas may also be caused by rape, in particular gang rape, and rape with foreign objects, as evidenced by the abnormally high number of women in conflict areas who have suffered fistulae.[1][2]
- In 2003, thousands of women in eastern Congo presented themselves for treatment of traumatic fistula caused by systematic, violent gang rape that occurred during the country's five years of war. So many cases have been reported that the destruction of the vagina is considered a war injury and recorded by doctors as a crime of combat.[3]
# Treatment
Treatment for fistulae varies depending on the cause and extent of the fistula, but often involves surgical intervention combined with antibiotic therapy.
Typically the first step in treating a fistula is an examination by a doctor to determine the extent and "path" that the fistula takes through the tissue.
In some cases the fistula is temporarily covered, for example a fistula caused by cleft palate is often treated with a palatal obturator to delay the need for surgery to a more appropriate age.
Surgery is often required to assure adequate drainage of the fistula (so that pus may escape without forming an abscess). Various surgical procedures are commonly used, most commonly fistulotomy, placement of a seton (a cord that is passed through the path of the fistula to keep it open for draining), or an endorectal flap procedure (where healthy tissue is pulled over the internal side of the fistula to keep feces or other material from reinfecting the channel). Treatments involving filling the fistula with fibrin glue or plugging it with plugs made of porcine small intestine submucosa have also been explored in recent years, with variable success. Surgery for anorectal fistulae is not without side effects, including recurrence, reinfection, and incontinence.
It is important to note that surgical treatment of a fistula without diagnosis or management of the underlying condition, if any, is not recommended. For example, surgical treatment of fistulae in Crohn's disease can be effective, but if the Crohn's disease itself is not treated, the rate of recurrence of fistula is very high (well above 50%).
# Therapeutic use
In end stage renal failure patients, a cimino fistula is often deliberately created in the arm by means of a short day surgery in order to permit easier withdrawal of blood for hemodialysis.
As a radical treatment for portal hypertension, surgical creation of a portacaval fistula produces an anastomosis between the hepatic portal vein and the inferior vena cava across the omental foramen (of Winslow). This spares the portal venous system from high pressure which can cause esophageal varices, caput madusae, and hemorrhoids. | https://www.wikidoc.org/index.php/Bowel_fistulae | |
07b2f02d86e867164fe80630cc61b0da280d6e96 | wikidoc | Brazing | Brazing
# Overview
Brazing is a joining process whereby a filler metal or alloy is heated to melting temperature above 450°C (842°F), or, by the traditional definition that has been used in the United States, above 800°F (425°C) and distributed between two or more close-fitting parts by capillary action. At its liquid temperature, the molten filler metal and flux interacts with a thin layer of the base metal, cooling to form a strong, sealed joint. By definition the melting temperature of the braze alloy is lower (sometimes substantially) than the melting temperature of the materials being joined. The brazed joint becomes a sandwich of different layers, each metallurgically linked to the adjacent layers. Common brazements are about 1/3 as strong as the parent materials due either to the inherent lower yield strength of the braze alloy or to the low fracture toughness of intermetallic components. To create high-strength brazes, a brazement can be annealed to homogenize the grain structure and composition (by diffusion) with that of the parent material.
# Variations in Definition
Brazing has historically been defined in many ways and is often confused with soldering. A defining characteristic is that the braze melts while the material(s) being joined do not. The distinction between brazing and soldering is largely semantic; brazing occurs at a higher temperature than soldering. One definition of brazing is “joining of two materials using a third, dissimilar material at higher temperatures than soldering.” While the exact temperature difference between brazing and soldering is often disputed, there are definite metallurgical reasons to use the 840°F figure. This is the official American Welding Society definition.
Braze alloy is often used to define an alloy that flows in thin joints while braze filler metal is used for thicker joints and for gap filling.
# Common techniques
## Furnace brazing
The furnace brazing method is accomplished by assembling the material to be brazed and the filler metal in the appropriate configurations and then placing the assembly in a furnace where it is heated uniformly.
Furnace brazing is practical when the brazing material can be in contact with the joint, and the part can survive uniform heating. This process is generally used for applications that need high volume production. When it is an applicable process, it offers the benefits of a controlled heat cycle, no post braze cleaning, and no skilled labor needed. The type of furnace used depends on whether batch or continuous operation is desired and can be designed to have a protective atmosphere to eliminate the need of protective flux in the filler metal. The type of atmosphere depends on the filler metal and the material being brazed. Common atmospheres used include hydrogen based and vacuum. In a hydrogen atmosphere, the gas cleans braze components and eliminates the need for flux. It is often mixed with inert gasses such as nitrogen, argon, or helium to lower the overall percentage of hydrogen in the furnace atmosphere. When a vacuum furnace is used, heat treating processes can be combined with the brazing process. Vacuum furnaces typically require a larger capital investment but also produce products of typically higher quality.
## Silver brazing
If silver alloy is used, brazing can be referred to as 'silver brazing'. Colloquially, the inaccurate terms "silver soldering" or "hard soldering" are used, to distinguish from the process of low temperature soldering that is done with solder having a melting point below 450 °C (842 °F), or, as traditionally defined in the United States, having a melting point below 800°F or 425°C. Silver brazing is similar to soldering but higher temperatures are used and the filler metal has a significantly different composition and higher melting point than solder. Silver brazing requires a gap not greater than a few micrometres or mils for proper capillary action during joining of parts. (Soldering also uses capillary action to fill small spaces, although the need for small gap distances may be less critical than in brazing.) This often requires parts to be silver brazed to be machined to close tolerances.
Brazing is widely used in the tool industry to fasten hardmetal (carbide, ceramics, cermet, and similar) tips to tools such as saw blades. “Pretinning” is often done: the braze alloy is melted onto the hardmetal tip, which is placed next to the steel and remelted. Pretinning gets around the problem that hardmetals are hard to wet.
Brazed hardmetal joints are typically two thousandths to seven thousandths of an inch thick. The braze alloy joins the materials and compensates for the difference in their expansion rates. In addition it provides a cushion between the hard carbide tip and the hard steel which softens impact and prevents tip loss and damage, much as the suspension on a vehicle helps prevent damage to both the tires and the vehicle. Finally the braze alloy joins the other two materials to create a composite structure, much as layers of wood and glue create plywood.
The standard for braze joint strength in many industries is a joint that is stronger than either base material, so that when under stress, one or other of the base materials fails before the joint fails.
One special silver brazing method is called Pinbrazing or Pin Brazing. It has been developed especially for connecting cables to railway track or for cathodic protection installations.
The method uses a silver and flux containing brazing pin which is melted down in the eye of a cable lug. The equipments are normally powered from batteries.
## Braze welding
In another similar usage, brazing is the use of a bronze or brass filler rod coated with flux together with an oxyacetylene torch to join pieces of steel. The American Welding Society prefers to use the term braze welding for this process, as capillary attraction is not involved, unlike the prior silver brazing example. Braze welding takes place at the melting temperature of the filler (e.g., 870 °C to 980 °C or 1600 °F to 1800 °F for bronze alloys) which is often considerably lower than the melting point of the base material (e.g., 1600 °C (2900 °F) for mild steel).
Braze welding has many advantages over fusion welding. It allows you to join dissimilar metals, to minimize heat distortion, and to reduce extensive pre- heating. Another side effect of braze welding is the elimination of stored-up stresses that are often present in fusion welding. This is extremely important in the repair of large castings. The disadvantages are the loss of strength when subjected to high temperatures and the inability to withstand high stresses.
The equipment needed for braze welding is basically identical to the equipment used in brazing. Since braze welding usually requires more heat than brazing, an oxyacetylene or oxy-mapp torch is recommended.
‘Braze welding’ is also used to mean the joining of plated parts to another material. Carbide, cermet and ceramic tips are plated and then joined to steel to make tipped band saws. The plating acts as a braze alloy.
## Cast iron "welding"
The "welding" of cast iron is usually a brazing operation, with a filler rod made chiefly of nickel being used although true welding with cast iron rods is also available.
## Vacuum brazing
Vacuum brazing is a materials joining technique that offers significant advantages: extremely clean, superior, flux-free braze joints of high integrity and strength. The process can be expensive because it must be performed inside a vacuum chamber vessel. Temperature uniformity is maintained on the work piece when heating in a vacuum, greatly reducing residual stresses due to slow heating and cooling cycles. This, in turn, can significantly improve the thermal and mechanical properties of the material, thus providing unique heat treatment capabilities. One such capability is heat-treating or age-hardening the workpiece while performing a metal-joining process, all in a single furnace thermal cycle.
Vacuum brazing is often conducted in a furnace; this means that several joints can be made at once because the whole workpiece reaches the brazing temperature. The heat is transferred using radiation, as many other methods cannot be used in a vacuum.
# Brazing fundamentals
In order to attain the highest strengths for brazed joints, parts must be closely fitted and the base metals must be exceptionally clean and free of oxides. For capillary action to be effective joint clearances of 50 to 150 µm (0.002 to 0.006 inch) are recommended. In braze-welding, where a thick bead is deposited, tolerances may be relaxed to 0.5 mm (0.020 inch). Cleaning of surfaces can be done in several ways. Whichever method is selected, it is vitally important to remove all grease, oils, and paint. For custom jobs and part work, this can often be done with fine sand paper or steel wool. In pure brazing (not braze welding), it is vitally important to use sufficiently fine abrasive. Coarse abrasive can lead to deep scoring that interferes with capillary action and final bond strength. Residual particulates from sanding should be thoroughly cleaned from pieces. In assembly line work, a "pickling bath" is often used to dissolve oxides chemically. Diluted sulfuric acid is often used. Pickling is also often employed on metals like aluminum that are particularly prone to oxidation.
Using an abrasive to clean oil or grease physically removes some of it just as any wiping would. However to get the parts clean it is necessary to use a saponifier that will change the oils and greases to soap. Oven cleaners and detergents work well.
## Flux
In most cases, flux is required to prevent oxides from forming while the metal is heated and also helps to spread out the metal that is used to seal the joint. The most common fluxes for bronze brazing are borax-based. The flux can be applied in a number of ways. It can be applied as a paste with a brush directly to the parts to be brazed. Commercial pastes can be purchased or made up from powder combined with water (or in some cases, alcohol). Brazing pastes are also commercially available, combining filler metal powder, flux powder, and a non-reacting vehicle binder. Alternatively, brazing rods can be heated and then dipped into dry flux powder to coat them in flux. Brazing rods can also be purchased with a coating of flux, or a flux core. In either case, the flux flows into the joint when the rod is applied to the heated joint. Using a special torch head, special flux powders can be blown onto the workpiece using the torch flame itself. Excess flux should be removed when the joint is completed. Flux left in the joint can lead to corrosion. During the brazing process, flux may char and adhere to the work piece. Often this is removed by quenching the still-hot workpiece in water (to loosen the flux scale), followed by wire brushing the remainder.
The flux chars and adheres to the workpiece when it is used up and / or overheated. Warm flux can be extremely tenacious. Once the flux has cooled to room temperature it is much easier to remove. The goal is to use enough flux and a proper heating cycle so that the flux is not all used up.
The flux does not interact with the materials being brazed but serves as a barrier and oxygen interceptor. It often has some cleaning properties including the ability to remove oxides but should not be counted on for this.
When hot quenching remember that you are in effect, heat treating the materials. Quenching will change material properties.
Many types of brazing flux contain toxic chemicals, sometimes very toxic. Silver brazing flux often contains Cadmium, which can cause very fast onset of metal fume fever (within minutes in extreme cases), especially if brazing fumes are inhaled due to inadequate ventilation. Due care must be taken with these materials to protect persons working, and also the environment.
## Brazing strength and joint geometry
Brazing is different from welding, where higher temperatures are used, the base material melts, and the filler material (if used at all) has the same composition as the base material. Given two joints with the same geometry, brazed joints are generally not as strong as welded joints although a properly designed and executed brazed joint can be stronger than the parent metal. Careful matching of joint geometry to the forces acting on the joint and properly maintained clearance between two mating parts can lead to very strong brazed joints. The butt joint is the weakest geometry for tensile forces. The lap joint is much stronger, as it resists through shearing action rather than tensile pull and its surface area is much larger. To get braze joints roughly equivalent in strength to a weld a general rule of thumb is to make the overlap equal to 3 times the thickness of the pieces of metal being joined.
## Filler materials
A variety of alloys of metals, including silver, tin, zinc, copper and others are used as filler for brazing processes. There are specific brazing alloys and fluxes recommended, depending on which metals are to be joined. Metals such as aluminum can be brazed, although aluminum requires more skill and special fluxes. It conducts heat much better than steel and is more prone to oxidation. Some metals, such as titanium, cannot be brazed because they are insoluble with other metals, or have an oxide layer that forms too quickly at high temperatures.
However Titanium can be prepared to be successfully brazed if the tendency for oxidation is allowed for. If the material is deoxidized and protected by plating, vacuum or other means then you have a chemically active surface that can make for very strong joints. This is not true with unprepared Titanium and the braze joint is a chemical join that is not dependent on the metal solubility.
Brazing filler material is commonly available as flux-coated rods, very similar to stick-welding electrodes. Typical sizes are 3 mm (1/8") diameter. Some widely available filler materials are:
- Nickel-Silver: Usually with blue flux coating. 600 MPa (85,000 psi) tensile strength, 680 - 950°C (1250-1750°F) working temperature. Used for carbon and alloy steels and most metals not including aluminum.
- Bronze: Available with white borax flux coating. 420 MPa (60,000 psi) tensile strength. 870°C (1600°F) working temperature. Used for copper, steel, galvanized metal, and other metals not including aluminum.
- Brass: Uncoated plain brass brazing rod is often used, but requires the use of some type of additional flux.
Nb Flux coating colours are manufacturer specific and do not indicate specific alloy types.
# Advantages of brazing
Although there is a popular belief that brazing is an inferior substitute for welding, it has advantages over welding in many situations. For example, brazing brass has a strength and hardness near that of mild steel and is much more corrosion-resistant. In some applications, brazing is highly preferred. For example, silver brazing is the customary method of joining high-reliability, controlled-strength corrosion-resistant piping such as a nuclear submarine's seawater coolant pipes. Silver brazed parts can also be precisely machined after joining, to hide the presence of the joint to all but the most discerning observers, whereas it is nearly impossible to machine welds having any residual slag present and still hide joints.
- The lower temperature of brazing and brass-welding is less likely to distort the work piece, significantly change the crystalline structure (create a heat affected zone) or induce thermal stresses. For example, when large iron castings crack, it is almost always impractical to repair them with welding. In order to weld cast-iron without recracking it from thermal stress, the work piece must be hot-soaked to 870°C (1600 °F). When a large (more than 50 kg (100 lb)) casting cracks in an industrial setting, heat-soaking it for welding is almost always impractical. Often the casting only needs to be watertight, or take mild mechanical stress. Brazing is the preferred repair method in these cases.
- The lower temperature associated with brazing vs. welding can increase joining speed and reduce fuel gas consumption.
- Brazing can be easier for beginners to learn than welding.
- For thin workpieces (e.g., sheet metal or thin-walled pipe) brazing is less likely to result in burn-through.
- Brazing can also be a cheap and effective technique for mass production. Components can be assembled with preformed plugs of filler material positioned at joints and then heated in a furnace or passed through heating stations on an assembly line. The heated filler then flows into the joints by capillary action.
- Braze-welded joints generally have smooth attractive beads that do not require additional grinding or finishing. The most common filler materials are gold in colour, but fillers that more closely match the color of the base materials can be used if appearance is important.
# Possible problems
A brazing operation may cause defects in the base metal, especially if it is in stress. This can be due either to the material not being properly annealed before brazing, or to thermal expansion stress during heating.
An example of this is the silver brazing of copper-nickel alloys, where even moderate stress in the base material causes intergranular penetration by molten filler material during brazing, resulting in cracking at the joint.
Any flux residues left after brazing (inside or out) must be thoroughly removed; otherwise, severe corrosion may eventually occur.
# Brazing processes
- Pinbrazing
- Block Brazing
- Diffusion Brazing
- Dip Brazing
- Exothermic Brazing
- Flow Brazing
- Furnace Brazing
- Induction Brazing
- Infrared Brazing
- Resistance Brazing
- Torch Brazing
- Twin Carbon Arc Brazing
- Vacuum Brazing
- alternatives to brazing include the use of a connector that does not require heat similar toLokring connectors used by most of the auto makers and larger appliance manufacturers | Brazing
# Overview
Brazing is a joining process whereby a filler metal or alloy is heated to melting temperature above 450°C (842°F), or, by the traditional definition that has been used in the United States, above 800°F (425°C) and distributed between two or more close-fitting parts by capillary action. At its liquid temperature, the molten filler metal and flux interacts with a thin layer of the base metal, cooling to form a strong, sealed joint. By definition the melting temperature of the braze alloy is lower (sometimes substantially) than the melting temperature of the materials being joined. The brazed joint becomes a sandwich of different layers, each metallurgically linked to the adjacent layers. Common brazements are about 1/3 as strong as the parent materials due either to the inherent lower yield strength of the braze alloy or to the low fracture toughness of intermetallic components. To create high-strength brazes, a brazement can be annealed to homogenize the grain structure and composition (by diffusion) with that of the parent material.
# Variations in Definition
Brazing has historically been defined in many ways and is often confused with soldering. A defining characteristic is that the braze melts while the material(s) being joined do not. The distinction between brazing and soldering is largely semantic; brazing occurs at a higher temperature than soldering. One definition of brazing is “joining of two materials using a third, dissimilar material at higher temperatures than soldering.” While the exact temperature difference between brazing and soldering is often disputed, there are definite metallurgical reasons to use the 840°F figure. This is the official American Welding Society definition.
Braze alloy is often used to define an alloy that flows in thin joints while braze filler metal is used for thicker joints and for gap filling.
# Common techniques
## Furnace brazing
The furnace brazing method is accomplished by assembling the material to be brazed and the filler metal in the appropriate configurations and then placing the assembly in a furnace where it is heated uniformly.
Furnace brazing is practical when the brazing material can be in contact with the joint, and the part can survive uniform heating.[1] This process is generally used for applications that need high volume production. When it is an applicable process, it offers the benefits of a controlled heat cycle, no post braze cleaning, and no skilled labor needed. The type of furnace used depends on whether batch or continuous operation is desired and can be designed to have a protective atmosphere to eliminate the need of protective flux in the filler metal. The type of atmosphere depends on the filler metal and the material being brazed. Common atmospheres used include hydrogen based and vacuum. In a hydrogen atmosphere, the gas cleans braze components and eliminates the need for flux. It is often mixed with inert gasses such as nitrogen, argon, or helium to lower the overall percentage of hydrogen in the furnace atmosphere. When a vacuum furnace is used, heat treating processes can be combined with the brazing process. Vacuum furnaces typically require a larger capital investment but also produce products of typically higher quality.[2]
## Silver brazing
If silver alloy is used, brazing can be referred to as 'silver brazing'. Colloquially, the inaccurate terms "silver soldering" or "hard soldering" are used, to distinguish from the process of low temperature soldering that is done with solder having a melting point below 450 °C (842 °F), or, as traditionally defined in the United States, having a melting point below 800°F or 425°C. Silver brazing is similar to soldering but higher temperatures are used and the filler metal has a significantly different composition and higher melting point than solder. Silver brazing requires a gap not greater than a few micrometres or mils for proper capillary action during joining of parts. (Soldering also uses capillary action to fill small spaces, although the need for small gap distances may be less critical than in brazing.) This often requires parts to be silver brazed to be machined to close tolerances.
Brazing is widely used in the tool industry to fasten hardmetal (carbide, ceramics, cermet, and similar) tips to tools such as saw blades. “Pretinning” is often done: the braze alloy is melted onto the hardmetal tip, which is placed next to the steel and remelted. Pretinning gets around the problem that hardmetals are hard to wet.
Brazed hardmetal joints are typically two thousandths to seven thousandths of an inch thick. The braze alloy joins the materials and compensates for the difference in their expansion rates. In addition it provides a cushion between the hard carbide tip and the hard steel which softens impact and prevents tip loss and damage, much as the suspension on a vehicle helps prevent damage to both the tires and the vehicle. Finally the braze alloy joins the other two materials to create a composite structure, much as layers of wood and glue create plywood.
The standard for braze joint strength in many industries is a joint that is stronger than either base material, so that when under stress, one or other of the base materials fails before the joint fails.
One special silver brazing method is called Pinbrazing or Pin Brazing. It has been developed especially for connecting cables to railway track or for cathodic protection installations.
The method uses a silver and flux containing brazing pin which is melted down in the eye of a cable lug. The equipments are normally powered from batteries.
## Braze welding
In another similar usage, brazing is the use of a bronze or brass filler rod coated with flux together with an oxyacetylene torch to join pieces of steel. The American Welding Society prefers to use the term braze welding for this process, as capillary attraction is not involved, unlike the prior silver brazing example. Braze welding takes place at the melting temperature of the filler (e.g., 870 °C to 980 °C or 1600 °F to 1800 °F for bronze alloys) which is often considerably lower than the melting point of the base material (e.g., 1600 °C (2900 °F) for mild steel).
Braze welding has many advantages over fusion welding. It allows you to join dissimilar metals, to minimize heat distortion, and to reduce extensive pre- heating. Another side effect of braze welding is the elimination of stored-up stresses that are often present in fusion welding. This is extremely important in the repair of large castings. The disadvantages are the loss of strength when subjected to high temperatures and the inability to withstand high stresses.
The equipment needed for braze welding is basically identical to the equipment used in brazing. Since braze welding usually requires more heat than brazing, an oxyacetylene or oxy-mapp torch is recommended.
‘Braze welding’ is also used to mean the joining of plated parts to another material. Carbide, cermet and ceramic tips are plated and then joined to steel to make tipped band saws. The plating acts as a braze alloy.
## Cast iron "welding"
The "welding" of cast iron is usually a brazing operation, with a filler rod made chiefly of nickel being used although true welding with cast iron rods is also available.
## Vacuum brazing
Vacuum brazing is a materials joining technique that offers significant advantages: extremely clean, superior, flux-free braze joints of high integrity and strength. The process can be expensive because it must be performed inside a vacuum chamber vessel. Temperature uniformity is maintained on the work piece when heating in a vacuum, greatly reducing residual stresses due to slow heating and cooling cycles. This, in turn, can significantly improve the thermal and mechanical properties of the material, thus providing unique heat treatment capabilities. One such capability is heat-treating or age-hardening the workpiece while performing a metal-joining process, all in a single furnace thermal cycle.
Vacuum brazing is often conducted in a furnace; this means that several joints can be made at once because the whole workpiece reaches the brazing temperature. The heat is transferred using radiation, as many other methods cannot be used in a vacuum.
# Brazing fundamentals
In order to attain the highest strengths for brazed joints, parts must be closely fitted and the base metals must be exceptionally clean and free of oxides. For capillary action to be effective joint clearances of 50 to 150 µm (0.002 to 0.006 inch) are recommended. In braze-welding, where a thick bead is deposited, tolerances may be relaxed to 0.5 mm (0.020 inch). Cleaning of surfaces can be done in several ways. Whichever method is selected, it is vitally important to remove all grease, oils, and paint. For custom jobs and part work, this can often be done with fine sand paper or steel wool. In pure brazing (not braze welding), it is vitally important to use sufficiently fine abrasive. Coarse abrasive can lead to deep scoring that interferes with capillary action and final bond strength. Residual particulates from sanding should be thoroughly cleaned from pieces. In assembly line work, a "pickling bath" is often used to dissolve oxides chemically. Diluted sulfuric acid is often used. Pickling is also often employed on metals like aluminum that are particularly prone to oxidation.
Using an abrasive to clean oil or grease physically removes some of it just as any wiping would. However to get the parts clean it is necessary to use a saponifier that will change the oils and greases to soap. Oven cleaners and detergents work well.
## Flux
In most cases, flux is required to prevent oxides from forming while the metal is heated and also helps to spread out the metal that is used to seal the joint. The most common fluxes for bronze brazing are borax-based. The flux can be applied in a number of ways. It can be applied as a paste with a brush directly to the parts to be brazed. Commercial pastes can be purchased or made up from powder combined with water (or in some cases, alcohol). Brazing pastes are also commercially available, combining filler metal powder, flux powder, and a non-reacting vehicle binder. Alternatively, brazing rods can be heated and then dipped into dry flux powder to coat them in flux. Brazing rods can also be purchased with a coating of flux, or a flux core. In either case, the flux flows into the joint when the rod is applied to the heated joint. Using a special torch head, special flux powders can be blown onto the workpiece using the torch flame itself. Excess flux should be removed when the joint is completed. Flux left in the joint can lead to corrosion. During the brazing process, flux may char and adhere to the work piece. Often this is removed by quenching the still-hot workpiece in water (to loosen the flux scale), followed by wire brushing the remainder.
The flux chars and adheres to the workpiece when it is used up and / or overheated. Warm flux can be extremely tenacious. Once the flux has cooled to room temperature it is much easier to remove. The goal is to use enough flux and a proper heating cycle so that the flux is not all used up.
The flux does not interact with the materials being brazed but serves as a barrier and oxygen interceptor. It often has some cleaning properties including the ability to remove oxides but should not be counted on for this.
When hot quenching remember that you are in effect, heat treating the materials. Quenching will change material properties.
Many types of brazing flux contain toxic chemicals, sometimes very toxic. Silver brazing flux often contains Cadmium, which can cause very fast onset of metal fume fever (within minutes in extreme cases), especially if brazing fumes are inhaled due to inadequate ventilation. Due care must be taken with these materials to protect persons working, and also the environment.
## Brazing strength and joint geometry
Brazing is different from welding, where higher temperatures are used, the base material melts, and the filler material (if used at all) has the same composition as the base material. Given two joints with the same geometry, brazed joints are generally not as strong as welded joints although a properly designed and executed brazed joint can be stronger than the parent metal. Careful matching of joint geometry to the forces acting on the joint and properly maintained clearance between two mating parts can lead to very strong brazed joints. The butt joint is the weakest geometry for tensile forces. The lap joint is much stronger, as it resists through shearing action rather than tensile pull and its surface area is much larger. To get braze joints roughly equivalent in strength to a weld a general rule of thumb is to make the overlap equal to 3 times the thickness of the pieces of metal being joined.
## Filler materials
A variety of alloys of metals, including silver, tin, zinc, copper and others are used as filler for brazing processes. There are specific brazing alloys and fluxes recommended, depending on which metals are to be joined. Metals such as aluminum can be brazed, although aluminum requires more skill and special fluxes. It conducts heat much better than steel and is more prone to oxidation. Some metals, such as titanium, cannot be brazed because they are insoluble with other metals, or have an oxide layer that forms too quickly at high temperatures.
However Titanium can be prepared to be successfully brazed if the tendency for oxidation is allowed for. If the material is deoxidized and protected by plating, vacuum or other means then you have a chemically active surface that can make for very strong joints. This is not true with unprepared Titanium and the braze joint is a chemical join that is not dependent on the metal solubility.
Brazing filler material is commonly available as flux-coated rods, very similar to stick-welding electrodes. Typical sizes are 3 mm (1/8") diameter. Some widely available filler materials are:
- Nickel-Silver: Usually with blue flux coating. 600 MPa (85,000 psi) tensile strength, 680 - 950°C (1250-1750°F) working temperature. Used for carbon and alloy steels and most metals not including aluminum.
- Bronze: Available with white borax flux coating. 420 MPa (60,000 psi) tensile strength. 870°C (1600°F) working temperature. Used for copper, steel, galvanized metal, and other metals not including aluminum.
- Brass: Uncoated plain brass brazing rod is often used, but requires the use of some type of additional flux.
Nb Flux coating colours are manufacturer specific and do not indicate specific alloy types.
# Advantages of brazing
Although there is a popular belief that brazing is an inferior substitute for welding, it has advantages over welding in many situations. For example, brazing brass has a strength and hardness near that of mild steel and is much more corrosion-resistant. In some applications, brazing is highly preferred. For example, silver brazing is the customary method of joining high-reliability, controlled-strength corrosion-resistant piping such as a nuclear submarine's seawater coolant pipes. Silver brazed parts can also be precisely machined after joining, to hide the presence of the joint to all but the most discerning observers, whereas it is nearly impossible to machine welds having any residual slag present and still hide joints.
- The lower temperature of brazing and brass-welding is less likely to distort the work piece, significantly change the crystalline structure (create a heat affected zone) or induce thermal stresses. For example, when large iron castings crack, it is almost always impractical to repair them with welding. In order to weld cast-iron without recracking it from thermal stress, the work piece must be hot-soaked to 870°C (1600 °F). When a large (more than 50 kg (100 lb)) casting cracks in an industrial setting, heat-soaking it for welding is almost always impractical. Often the casting only needs to be watertight, or take mild mechanical stress. Brazing is the preferred repair method in these cases.
- The lower temperature associated with brazing vs. welding can increase joining speed and reduce fuel gas consumption.
- Brazing can be easier for beginners to learn than welding.
- For thin workpieces (e.g., sheet metal or thin-walled pipe) brazing is less likely to result in burn-through.
- Brazing can also be a cheap and effective technique for mass production. Components can be assembled with preformed plugs of filler material positioned at joints and then heated in a furnace or passed through heating stations on an assembly line. The heated filler then flows into the joints by capillary action.
- Braze-welded joints generally have smooth attractive beads that do not require additional grinding or finishing. The most common filler materials are gold in colour, but fillers that more closely match the color of the base materials can be used if appearance is important.
# Possible problems
A brazing operation may cause defects in the base metal, especially if it is in stress. This can be due either to the material not being properly annealed before brazing, or to thermal expansion stress during heating.
An example of this is the silver brazing of copper-nickel alloys, where even moderate stress in the base material causes intergranular penetration by molten filler material during brazing, resulting in cracking at the joint.
Any flux residues left after brazing (inside or out) must be thoroughly removed; otherwise, severe corrosion may eventually occur.
# Brazing processes
- Pinbrazing
- Block Brazing
- Diffusion Brazing
- Dip Brazing
- Exothermic Brazing
- Flow Brazing
- Furnace Brazing
- Induction Brazing
- Infrared Brazing
- Resistance Brazing
- Torch Brazing
- Twin Carbon Arc Brazing
- Vacuum Brazing
- alternatives to brazing include the use of a connector that does not require heat similar toLokring connectors used by most of the auto makers and larger appliance manufacturers | https://www.wikidoc.org/index.php/Brazing | |
6f7331cbbd3e6619cc27ff7084577f9597a7bdaa | wikidoc | Sternum | Sternum
# Overview
The sternum (from Greek στέρνον, sternon, "chest" and hebrew pronounced "Shamokin" also meaning chest) or breastbone is a long, flat bone located in the center of the thorax (chest). It connects to the rib bones via cartilage, forming the rib cage with them, and thus helps to protect the lungs, heart and major blood vessels from physical trauma.
The sternum is sometimes cut open (a median sternotomy) to gain access to the thoracic contents when performing cardiothoracic surgery.
The sternum is an elongated, flattened bone, forming the middle portion of the anterior wall of the thorax. Its upper end supports the clavicles (Collar bones), and its margins articulate with the cartilages of the first seven pairs of ribs. Its top is also connected to the Sternocleidomastoid muscle. It consists of three parts, from above downward:
- Manubrium
- Body of sternum (gladiolus)
- Xiphoid process
In early life, the body of sternum consists of four segments or sternebrœ.
In its natural position, the inclination of the bone is oblique from above, downward and forward. It is slightly convex in front and concave behind; broad above, becoming narrowed at the point where the manubrium joins the body, after which it again widens a little to below the middle of the body, and then narrows to its lower extremity. Its average length in the adult is about 17 cm, and is rather longer in the male than in the female.
# Structure
The sternum is composed of highly vascular cancellous tissue, covered by a thin layer of compact bone which is thickest in the manubrium between the articular facets for the clavicles.
# Articulations
The sternum articulates on either side with the clavicle and upper seven costal cartilages.
# Fractures of the sternum
Fractures of the sternum are not common. However, they may result from trauma, such as when a driver's chest is forced into the steering column of a car in a car accident. A fracture of the sternum is usually a comminuted fracture, meaning it is broken into pieces. The most common site of sternal fractures is at the sternal angle.
# Additional images
- Anterior surface of sternum and costal cartilages. | Sternum
Template:Infobox Bone
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
# Overview
The sternum (from Greek στέρνον, sternon, "chest" and hebrew pronounced "Shamokin" also meaning chest) or breastbone is a long, flat bone located in the center of the thorax (chest). It connects to the rib bones via cartilage, forming the rib cage with them, and thus helps to protect the lungs, heart and major blood vessels from physical trauma.
The sternum is sometimes cut open (a median sternotomy) to gain access to the thoracic contents when performing cardiothoracic surgery.
The sternum is an elongated, flattened bone, forming the middle portion of the anterior wall of the thorax. Its upper end supports the clavicles (Collar bones), and its margins articulate with the cartilages of the first seven pairs of ribs. Its top is also connected to the Sternocleidomastoid muscle. It consists of three parts, from above downward:
- Manubrium
- Body of sternum (gladiolus)
- Xiphoid process
In early life, the body of sternum consists of four segments or sternebrœ.
In its natural position, the inclination of the bone is oblique from above, downward and forward. It is slightly convex in front and concave behind; broad above, becoming narrowed at the point where the manubrium joins the body, after which it again widens a little to below the middle of the body, and then narrows to its lower extremity. Its average length in the adult is about 17 cm, and is rather longer in the male than in the female.
# Structure
The sternum is composed of highly vascular cancellous tissue, covered by a thin layer of compact bone which is thickest in the manubrium between the articular facets for the clavicles.
# Articulations
The sternum articulates on either side with the clavicle and upper seven costal cartilages.
# Fractures of the sternum
Fractures of the sternum are not common. However, they may result from trauma, such as when a driver's chest is forced into the steering column of a car in a car accident. A fracture of the sternum is usually a comminuted fracture, meaning it is broken into pieces. The most common site of sternal fractures is at the sternal angle.
# Additional images
- Anterior surface of sternum and costal cartilages. | https://www.wikidoc.org/index.php/Breast_bone | |
228aa98fc320ca86cc972f5a0f4f565b8cadf8d3 | wikidoc | Esmolol | Esmolol
- Dosing Information
- Esmolol is administered by continuous intravenous infusion with or without a loading dose. Additional loading doses and/or titration of the maintenance infusion (step-wise dosing) may be necessary based on desired ventricular response.
- In the absence of loading doses, continuous infusion of a single concentration of esmolol reaches pharmacokinetic and pharmacodynamic steady-state in about 30 minutes.
- The effective maintenance dose for continuous and step-wise dosing is 50 to 200 mcg per kg per minute, although doses as low as 25 mcg per kg per minute have been adequate. Dosages greater than 200 mcg per kg per minute provide little added heart rate lowering effect, and the rate of adverse reactions increases.
- Maintenance infusions may be continued for up to 48 hours.
- Dosing Information
- In this setting it is not always advisable to slowly titrate to a therapeutic effect. Therefore two dosing options are presented: immediate control and gradual control.
- Administer 1 mg per kg as a bolus dose over 30 seconds followed by an infusion of 150 mcg per kg per min if necessary.
- Adjust the infusion rate as required to maintain desired heart rate and blood pressure. Refer to Maximum Recommended Doses below.
- Administer 500 mcg per kg as a bolus dose over 1 minute followed by a maintenance infusion of 50 mcg per kg per min for 4 minutes.
- Depending on the response obtained, continue dosing as outlined for supraventricular tachycardia. Refer to Maximum Recommended Doses below.
- For the treatment of tachycardia, maintenance infusion dosages greater than 200 mcg per kg per min are not recommended; dosages greater than 200 mcg per kg per min provide little additional heart rate-lowering effect, and the rate of adverse reactions increases.
- For the treatment of hypertension, higher maintenance infusion dosages (250-300 mcg per kg per min) may be required. The safety of doses above 300 mcg per kg per minute has not been studied.
- After patients achieve adequate control of the heart rate and a stable clinical status, transition to alternative antiarrhythmic drugs may be accomplished.
- When transitioning from esmolol to alternative drugs, the physician should carefully consider the labeling instructions of the alternative drug selected and reduce the dosage of esmolol as follows:
- Thirty minutes following the first dose of the alternative drug, reduce the esmolol infusion rate by one-half (50%).
- After administration of the second dose of the alternative drug, monitor the patient’s response and if satisfactory control is maintained for the first hour, discontinue the esmolol infusion.
- Esmolol injection is available in a pre-mixed bag and ready-to-use vial. Esmolol is not compatible with Sodium Bicarbonate (5%) solution (limited stability) or furosemide (precipitation).
- Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.
Premixed Bag
- The medication port is to be used solely for withdrawing an initial bolus from the bag.
- Use aseptic technique when withdrawing the bolus dose.
- Do not add any additional medications to the bag.
Ready-to-Use Vial
- The Ready-to-use Vial may be used to administer a loading dosage by hand-held syringe while the maintenance infusion is being prepared.
- Developed by: AHA/ACC/HRS
- IV bolus of 500 mcg/kg administered over 1 min followed by IV infusion of 50–300 mcg/kg/min
- Dosing Information
- Initial dose of 500 mcg/kg/min over 1 minute, then a titrated infusion to a dose of 50 to 300 mcg/kg/min administered over 4 minutes.
- Dosing Information
- 1 mg/kg bolus followed by 250 mcg/kg/min in association with propofol.
- Dosing Information
- 80 mg IV
- Dosing Information
- 100 mg bolus into the aortic root administered followed by a 10 to 15 mg/min infusion as many times as required.
- Dosing Information
- 10 mg/mL.
- Dosing Information
- Initial dose of 500 mcg/kg administered over 1 minute, then 50 mcg/kg/min and titrated up to a maximum of 200 mcg/kg/min in 50 mcg/kg/min increments every 4 minutes.
- Severe sinus bradycardia: May precipitate or worsen bradycardia resulting in cardiogenic shock and cardiac arrest.
- Heart block greater than first degree: Second- or third-degree atrioventricular block may precipitate or worsen bradycardia resulting in cardiogenic shock and cardiac arrest.
- Sick sinus syndrome: May precipitate or worsen bradycardia resulting in cardiogenic shock and cardiac arrest.
- Decompensated heart failure: May worsen heart failure.
- Cardiogenic shock: May precipitate further cardiovascular collapse and cause cardiac arrest.
- IV administration of cardiodepressant calcium channel blockers (e.g., verapamil) and esmolol in close proximity (i.e., while cardiac effects from the other are still present); fatal cardiac arrests have occurred in patients receiving esmolol and intravenous verapamil.
- Pulmonary hypertension: May precipitate cardiorespiratory compromise.
- Hypersensitivity reactions, including anaphylaxis to esmolol or any of the inactive ingredients of the product (cross-sensitivity between beta blockers is possible).
Hypotension can occur at any dose but is dose-related. Patients with hemodynamic compromise or on interacting medications are at particular risk. Severe reactions may include loss of consciousness, cardiac arrest, and death. For control of ventricular heart rate, maintenance doses greater than 200 mcg per kg per min are not recommended. Monitor patients closely, especially if pretreatment blood pressure is low. In case of an unacceptable drop in blood pressure, reduce or stop esmolol injection. Decrease of dose or termination of infusion reverses hypotension, usually within 30 minutes.
Bradycardia, including sinus pause, heart block, severe bradycardia, and cardiac arrest have occurred with the use of esmolol injection. Patients with first-degree atrioventricular block, sinus node dysfunction, or conduction disorders may be at increased risk. Monitor heart rate and rhythm in patients receiving esmolol.
If severe bradycardia develops, reduce or stop esmolol.
Beta blockers, like esmolol injection, can cause depression of myocardial contractility and may precipitate heart failure and cardiogenic shock. At the first sign or symptom of impending cardiac failure, stop esmolol and start supportive therapy.
Monitor vital signs closely and titrate esmolol slowly in the treatment of patients whose blood pressure is primarily driven by vasoconstriction associated with hypothermia.
Patients with reactive airways disease should, in general, not receive beta blockers. Because of its relative beta1 selectivity and titratability, titrate esmolol to the lowest possible effective dose. In the event of bronchospasm, stop the infusion immediately; a beta2 stimulating agent may be administered with appropriate monitoring of ventricular rates.
In patients with hypoglycemia, or diabetic patients (especially those with labile diabetes) who are receiving insulin or other hypoglycemic agents, beta blockers may mask tachycardia occurring with hypoglycemia, but other manifestations such as dizziness and sweating may not be masked.
Concomitant use of beta blockers and antidiabetic agents can enhance the effect of antidiabetic agents (blood glucose–lowering).
Infusion site reactions have occurred with the use of esmolol injection. They include irritation, inflammation, and severe reactions (thrombophlebitis, necrosis, and blistering), in particular when associated with extravasation. Avoid infusions into small veins or through a butterfly catheter.
If a local infusion site reaction develops, use an alternative infusion site and avoid extravasation.
Beta blockers may exacerbate anginal attacks in patients with Prinzmetal’s angina because of unopposed alpha receptor–mediated coronary artery vasoconstriction. Do not use nonselective beta blockers.
If esmolol is used in the setting of pheochromocytoma, give it in combination with an alpha-blocker, and only after the alpha-blocker has been initiated. Administration of beta-blockers alone in the setting of pheochromocytoma has been associated with a paradoxical increase in blood pressure from the attenuation of beta-mediated vasodilation in skeletal muscle.
In hypovolemic patients, esmolol injection can attenuate reflex tachycardia and increase the risk of hypotension.
In patients with peripheral circulatory disorders (including Raynaud’s disease or syndrome, and peripheral occlusive vascular disease), esmolol may aggravate peripheral circulatory disorders.
Severe exacerbations of angina, myocardial infarction, and ventricular arrhythmias have been reported in patients with coronary artery disease upon abrupt discontinuation of beta blocker therapy. Observe patients for signs of myocardial ischemia when discontinuing esmolol.
Heart rate increases moderately above pretreatment levels 30 minutes after esmolol discontinuation.
Beta blockers, including esmolol, have been associated with increases in serum potassium levels and hyperkalemia. The risk is increased in patients with risk factors such as renal impairment. Intravenous administration of beta blockers has been reported to cause potentially life-threatening hyperkalemia in hemodialysis patients. Monitor serum electrolytes during therapy with esmolol.
Beta blockers, including esmolol, have been reported to cause hyperkalemic renal tubular acidosis. Acidosis in general may be associated with reduced cardiac contractility.
Beta-adrenergic blockade may mask certain clinical signs (e.g., tachycardia) of hyperthyroidism. Abrupt withdrawal of beta blockade might precipitate a thyroid storm; therefore, monitor patients for signs of thyrotoxicosis when withdrawing beta blocking therapy.
When using beta blockers, patients at risk of anaphylactic reactions may be more reactive to allergen exposure (accidental, diagnostic, or therapeutic).
Patients using beta blockers may be unresponsive to the usual doses of epinephrine used to treat anaphylactic or anaphylactoid reactions.
- Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.
- The following adverse reaction rates are based on use of esmolol in clinical trials involving 369 patients with supraventricular tachycardia and over 600 intraoperative and postoperative patients enrolled in clinical trials. Most adverse effects observed in controlled clinical trial settings have been mild and transient. The most important and common adverse effect has been hypotension. Deaths have been reported in post-marketing experience occurring during complex clinical states where esmolol was presumably being used simply to control ventricular rate
- Confusional state and agitation (~2%)
- Anxiety, depression and abnormal thinking (<1%)
- Headache (~ 2%)
- Paresthesia, syncope, speech disorder, and lightheadedness (<1%)
- Convulsions (<1%), with one death
- Peripheral ischemia (~1%)
- Pallor and flushing (<1%)
- Vomiting (~1%)
- Dyspepsia, constipation, dry mouth, and abdominal discomfort (<1%)
- Urinary retention (<1%)
# Cardiac Disorders
- Cardiac arrest, Coronary arteriospasm
# Skin and Subcutaneous Tissue Disorders
- Angioedema, Urticaria, Psoriasis
- Digitalis glycosides: Concomitant administration of digoxin and esmolol leads to an approximate 10% to 20% increase of digoxin blood levels at some time points. Digoxin does not affect esmolol pharmacokinetics. Both digoxin and beta blockers slow atrioventricular conduction and decrease the heart rate. Concomitant use increases the risk of bradycardia.
- Anticholinesterases: esmolol prolonged the duration of succinylcholine-induced neuromuscular blockade and moderately prolonged clinical duration and recovery index of mivacurium.
- Antihypertensive agents clonidine, guanfacine, or moxonidine: Beta blockers also increase the risk of clonidine-, guanfacine-, or moxonidine-withdrawal rebound hypertension. If, during concomitant use of a beta blocker, antihypertensive therapy needs to be interrupted or discontinued, discontinue the beta blocker first, and the discontinuation should be gradual.
- Calcium channel antagonists: In patients with depressed myocardial function, use of esmolol with cardiodepressant calcium channel antagonists (e.g., verapamil) can lead to fatal cardiac arrests.
- Sympathomimetic drugs: Sympathomimetic drugs having beta-adrenergic agonist activity will counteract effects of esmolol.
- Vasoconstrictive and positive inotropic agents: Because of the risk of reducing cardiac contractility in presence of high systemic vascular resistance, do not use esmolol to control tachycardia in patients receiving drugs that are vasoconstrictive and have positive inotropic effects, such as epinephrine, norepinephrine, and dopamine.
- Teratogenicity studies in rats at intravenous dosages of esmolol hydrochloride up to 3000 mcg/kg/min (10 times the maximum human maintenance dosage) for 30 minutes daily produced no evidence of maternal toxicity, embryotoxicity or teratogenicity, while a dosage of 10,000 mcg/kg/min produced maternal toxicity and lethality. In rabbits, intravenous dosages up to 1000 mcg/kg/min for 30 minutes daily produced no evidence of maternal toxicity, embryotoxicity or teratogenicity, while 2500 mcg/kg/min produced minimal maternal toxicity and increased fetal resorptions.
- Monitor patients closely, especially if pretreatment blood pressure is low. In case of an unacceptable drop in blood pressure, reduce or stop esmolol injection. Decrease of dose or termination of infusion reverses hypotension, usually within 30 minutes.
- Monitor heart rate and rhythm in patients receiving esmolol.
- In patients with intraoperative and postoperative tachycardia and/or hypertension monitor vital signs closely and titrate smolol slowly in the treatment of patients whose blood pressure is primarily driven by vasoconstriction associated with hypothermia.
- Monitor serum electrolytes during therapy with esmolol.
- Monitor patients for signs of thyrotoxicosis when withdrawing beta blocking therapy.
- Dextrose (5%) Injection, USP
- Dextrose (5%) in Lactated Ringer’s Injection
- Dextrose (5%) in Ringer’s Injection
- Dextrose (5%) and Sodium Chloride (0.45%) Injection, USP
- Dextrose (5%) and Sodium Chloride (0.9%) Injection, USP
- Lactated Ringer’s Injection, USP
- Potassium Chloride (40 mEq/liter) in Dextrose (5%) Injection, USP
- Sodium Chloride (0.45%) Injection, USP
- Sodium Chloride (0.9%) Injection, USP
Overdoses of esmolol can cause cardiac and central nervous system effects. These effects may precipitate severe signs, symptoms, sequelae, and complications (for example, severe cardiac and respiratory failure, including shock and coma), and may be fatal. Continuous monitoring of the patient is required.
Cardiac effects
- Bradycardia,atrioventricular block (1st -, 2nd -, 3rd degree), junctional rhythms, intraventricular conduction delays, decreased cardiac contractility,hypotension, cardiac failure (including cardiogenic shock), cardiac arrest/asystole, and pulseless electrical activity.
Central nervous system
- Respiratory depression,seizures, sleep and mood disturbances, fatigue, lethargy, and coma.
- In addition, bronchospasm, mesenteric ischemia, peripheral cyanosis, hyperkalemia, and hypoglycemia (especially in children) may occur.
- Because of its approximately 9-minute elimination half-life, the first step in the management of toxicity should be to discontinue the esmolol infusion. Then, based on the observed clinical effects, consider the following general measures.
- Consider intravenous administration of atropine or another anticholinergic drug or cardiac pacing.
- Consider intravenous administration of a diuretic or digitalis glycoside. In shock resulting from inadequate cardiac contractility, consider intravenous administration of dopamine, dobutamine, isoproterenol, or inamrinone. Glucagon has been reported to be useful.
- Consider intravenous administration of fluids or vasopressor agents such as dopamine or norepinephrine.
- Consider intravenous administration of a beta 2 stimulating agent or a theophylline derivative.
- Massive accidental overdoses of esmolol have resulted from dilution errors. The use of esmolol premixed injection may reduce the potential for dilution errors. Some of these overdoses have been fatal while others resulted in permanent disability. Bolus doses in the range of 625 mg to 2.5 g (12.5-50 mg/kg) have been fatal. Patients have recovered completely from overdoses as high as 1.75 g given over one minute or doses of 7.5 g given over one hour for cardiovascular surgery. The patients who survived appear to be those whose circulation could be supported until the effects of esmolol resolved.
Its elimination half-life after intravenous infusion is approximately 9 minutes. esmolol inhibits the beta1 adrenergic receptors located chiefly in cardiac muscle, but this preferential effect is not absolute and at higher doses it begins to inhibit beta2 adrenergic receptors located chiefly in the bronchial and vascular musculature.
(±)-Methyl p- hydrocinnamate hydrochloride and has the following structure:
Esmolol hydrochloride has the empirical formula C16H26NO4Cl and a molecular weight of 331.8. It has one asymmetric center and exists as an enantiomeric pair.
Esmolol hydrochloride is a white to off-white crystalline powder. It is a relatively hydrophilic compound which is very soluble in water and freely soluble in alcohol. Its partition coefficient (octanol/water) at pH 7.0 is 0.42 compared to 17.0 for propranolol.
All esmolol presentations are clear, colorless to light yellow, sterile, nonpyrogenic, iso-osmotic solutions of esmolol hydrochloride in sodium chloride. The formulations for esmolol premixed injection, esmolol double strength injection, and esmolol injection are described in the table below:
The calculated osmolarity of esmolol premixed injection and esmolol double strength injection is 312 mOsmol/L. The 250 mL and 100 mL bags are non-latex, non-PVC INTRAVIA bags with dual PVC ports. The INTRAVIA bags are manufactured from a specially designed multilayer plastic (PL 2408). Solutions in contact with the plastic container leach out certain chemical compounds from the plastic in very small amounts; however, biological testing was supportive of the safety of the plastic container materials.
In human electrophysiology studies, esmolol produced effects typical of a beta blocker: a decrease in the heart rate, increase in sinus cycle length, prolongation of the sinus node recovery time, prolongation of the AH interval during normal sinus rhythm and during atrial pacing, and an increase in antegrade Wenckebach cycle length.
In patients undergoing radionuclide angiography, esmolol, at dosages of 200 mcg/kg/min, produced reductions in heart rate, systolic blood pressure, rate pressure product, left and right ventricular ejection fraction and cardiac index at rest, which were similar in magnitude to those produced by intravenous propranolol (4 mg). During exercise, esmolol produced reductions in heart rate, rate pressure product and cardiac index which were also similar to those produced by propranolol, but esmolol produced a significantly larger fall in systolic blood pressure. In patients undergoing cardiac catheterization, the maximum therapeutic dose of 300 mcg/kg/min of esmolol produced similar effects and, in addition, there were small, clinically insignificant increases in the left ventricular end diastolic pressure and pulmonary capillary wedge pressure. At 30 minutes after the discontinuation of esmolol infusion, all of the hemodynamic parameters had returned to pretreatment levels.
The relative cardioselectivity of esmolol was demonstrated in 10 mildly asthmatic patients. Infusions of esmolol 100, 200 and 300 mcg/kg/min produced no significant increases in specific airway resistance compared to placebo. At 300 mcg/kg/min, esmolol produced slightly enhanced bronchomotor sensitivity to dry air stimulus. These effects were not clinically significant, and esmolol was well tolerated by all patients. Six of the patients also received intravenous propranolol, and at a dosage of 1 mg, two experienced significant, symptomatic bronchospasm requiring bronchodilator treatment. One otherpropranolol-treated patient also experienced dry air-induced bronchospasm. No adverse pulmonary effects were observed in patients with COPD who received therapeutic dosages of esmolol for treatment of supraventricular tachycardia (51 patients) or in perioperative settings (32 patients).
Using an appropriate loading dose, steady-state blood levels of esmolol for dosages from 50-300 mcg/kg/min are obtained within five minutes. Steady-state is reached in about 30 minutes without the loading dose. Steady-state blood levels of esmolol increase linearly over this dosage range and elimination kinetics are dose-independent over this range. Steady-state blood levels are maintained during infusion but decrease rapidly after termination of the infusion. Because of its short half-life, blood levels of esmolol can be rapidly altered by increasing or decreasing the infusion rate and rapidly eliminated by discontinuing the infusion.
Consistent with the high rate of blood-based metabolism of esmolol, less than 2% of the drug is excreted unchanged in the urine. Within 24 hours of the end of infusion, the acid metabolite of esmolol in urine accounts for approximately 73-88% of the dosage.
Metabolism of esmolol results in the formation of the corresponding free acid and methanol. The acid metabolite has been shown in animals to have negligible activity and in normal volunteers its blood levels do not correspond to the level of beta blockade. The acid metabolite has an elimination half-life of about 3.7 hours and is excreted in the urine with a clearance approximately equivalent to the glomerular filtration rate. After a 4 hour maintenance infusion of 150 mcg/kg, the plasma concentrations of esmolol are similar in subjects with normal renal function and in patients with ESRD on dialysis. The half-life of the acid metabolite of esmolol, which is primarily excreted unchanged by the kidney, is increased about 12-fold to 48 hours in patients with ESRD. The peak concentrations of the acid metabolite are doubled in ESRD.
Methanol blood levels, monitored in subjects receiving esmolol for up to 6 hours at 300 mcg/kg/min and 24 hours at 150 mcg/kg/min, approximated endogenous levels and were less than 2% of levels usually associated with methanol toxicity.
Esmolol has been shown to be 55% bound to human plasma protein, while the acid metabolite is only 10% bound.
In two multicenter, randomized, double-blind, controlled comparisons of esmolol injection with placebo and propranolol, maintenance doses of 50 to 300 mcg/kg/min of esmolol were found to be more effective than placebo and about as effective as propranolol, 3-6 mg given by bolus injections, in the treatment of supraventricular tachycardia, principally atrial fibrillation and atrial flutter. The majority of these patients developed their arrhythmias postoperatively. About 60-70% of the patients treated with esmolol developed either a 20% reduction in heart rate, a decrease in heart rate to less than 100 bpm, or, rarely, conversion to normal sinus rhythm and about 95% of these patients did so at a dosage of 200 mcg/kg/min or less. The average effective dosage of esmolol was approximately 100 mcg/kg/min in the two studies. Other multicenter baseline-controlled studies gave similar results. In the comparison with propranolol, about 50% of patients in both the esmolol and propranolol groups were on concomitant digoxin. Response rates were slightly higher with both beta blockers in the digoxin-treated patients.
In all studies significant decreases of blood pressure occurred in 20-50% of patients, identified either as adverse reaction reports by investigators, or by observation of systolic pressure less than 90 mmHg or diastolic pressure less than 50 mmHg. The hypotension was symptomatic (mainly hyperhidrosis or dizziness) in about 12% of patients, and therapy was discontinued in about 11% of patients, about half of whom were symptomatic. Hypotension was more common with esmolol (53%) than with propranolol (17%). The hypotension was rapidly reversible with decreased infusion rate or after discontinuation of therapy with esmolol. For both esmolol and propranolol, hypotension was reported less frequently in patients receiving concomitant digoxin.
NDC 10019-055-61, 2500 mg / 250 mL (10 mg/mL) Ready-to-use INTRAVIA Bags
- BREVIBLOC DOUBLE STRENGTH PREMIXED Injection
NDC 10019-075-87, 2000 mg / 100 mL (20 mg/mL) Ready-to-use INTRAVIA Bags
- BREVIBLOC Injection
NDC 10019-115-01, 100 mg / 10 mL (10 mg/mL) Ready-to-use Vials, Package of 25
- Each bag contains no preservative. Once drug has been withdrawn from ready-to-use bag, the bag should be used within 24 hours, with any unused portion discarded.
- Do not use plastic containers in series connections. Such use could result in an embolism due to residual air being drawn from the primary container before administration of the fluid from the secondary container is completed.
- Do not remove unit from overwrap until ready to use. Do not use if overwrap has been previously opened or damaged. The overwrap is a moisture barrier. The inner bag maintains sterility of the solution. Tear overwrap at notch and remove premixed bag. Some opacity of the plastic due to moisture absorption during the sterilization process may be observed. This is normal and does not affect the solution quality or safety. The opacity will diminish gradually.
- Check for minute leaks by squeezing the inner bag firmly. If leaks are found, discard solution, as sterility may be impaired. Do not use unless the solution is clear (colorless to light yellow) and the seal is intact.
- The most common adverse reactions are symptomatic hypotension (hyperhidrosis, dizziness), and asymptomatic hypotension.
- Esmolol HCl
- ↑ January CT, Wann LS, Alpert JS, Calkins H, Cleveland JC, Cigarroa JE; et al. (2014). "2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society". J Am Coll Cardiol. doi:10.1016/j.jacc.2014.03.022. PMID 24685669.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link) .mw-parser-output cite.citation{font-style:inherit}.mw-parser-output q{quotes:"\"""\"""'""'"}.mw-parser-output code.cs1-code{color:inherit;background:inherit;border:inherit;padding:inherit}.mw-parser-output .cs1-lock-free a{background:url("")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-limited a,.mw-parser-output .cs1-lock-registration a{background:url("")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-subscription a{background:url("")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration{color:#555}.mw-parser-output .cs1-subscription span,.mw-parser-output .cs1-registration span{border-bottom:1px dotted;cursor:help}.mw-parser-output .cs1-hidden-error{display:none;font-size:100%}.mw-parser-output .cs1-visible-error{display:none;font-size:100%}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration,.mw-parser-output .cs1-format{font-size:95%}.mw-parser-output .cs1-kern-left,.mw-parser-output .cs1-kern-wl-left{padding-left:0.2em}.mw-parser-output .cs1-kern-right,.mw-parser-output .cs1-kern-wl-right{padding-right:0.2em}
- ↑ Mooss AN, Hilleman DE, Mohiuddin SM, Hunter CB (1994). "Safety of esmolol in patients with acute myocardial infarction treated with thrombolytic therapy who had relative contraindications to beta-blocker therapy". Ann Pharmacother. 28 (6): 701–3. PMID 7919552.CS1 maint: Multiple names: authors list (link)
- ↑ Johansen JW, Flaishon R, Sebel PS (1997). "Esmolol reduces anesthetic requirement for skin incision during propofol/nitrous oxide/morphine anesthesia". Anesthesiology. 86 (2): 364–71. PMID 9054254.CS1 maint: Multiple names: authors list (link)
- ↑ van den Broek WW, Leentjens AF, Mulder PG, Kusuma A, Bruijn JA (1999). "Low-dose esmolol bolus reduces seizure duration during electroconvulsive therapy: a double-blind, placebo-controlled study". Br J Anaesth. 83 (2): 271–4. PMID 10618942.CS1 maint: Multiple names: authors list (link)
- ↑ Mehlhorn U, Sauer H, Kuhn-Régnier F, Südkamp M, Dhein S, Eberhardt F; et al. (1999). "Myocardial beta-blockade as an alternative to cardioplegic arrest during coronary artery surgery". Cardiovasc Surg. 7 (5): 549–57. PMID 10499899.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
- ↑ Zakowski M, Kaufman B, Berguson P, Tissot M, Yarmush L, Turndorf H (1989). "Esmolol use during resection of pheochromocytoma: report of three cases". Anesthesiology. 70 (5): 875–7. PMID 2566290.CS1 maint: Multiple names: authors list (link)
- ↑ Duggal J, Singh S, Kuchinic P, Butler P, Arora R (2006). "Utility of esmolol in thyroid crisis". Can J Clin Pharmacol. 13 (3): e292–5. PMID 17127774.CS1 maint: Multiple names: authors list (link) | Esmolol
- Dosing Information
- Esmolol is administered by continuous intravenous infusion with or without a loading dose. Additional loading doses and/or titration of the maintenance infusion (step-wise dosing) may be necessary based on desired ventricular response.
- In the absence of loading doses, continuous infusion of a single concentration of esmolol reaches pharmacokinetic and pharmacodynamic steady-state in about 30 minutes.
- The effective maintenance dose for continuous and step-wise dosing is 50 to 200 mcg per kg per minute, although doses as low as 25 mcg per kg per minute have been adequate. Dosages greater than 200 mcg per kg per minute provide little added heart rate lowering effect, and the rate of adverse reactions increases.
- Maintenance infusions may be continued for up to 48 hours.
- Dosing Information
- In this setting it is not always advisable to slowly titrate to a therapeutic effect. Therefore two dosing options are presented: immediate control and gradual control.
- Administer 1 mg per kg as a bolus dose over 30 seconds followed by an infusion of 150 mcg per kg per min if necessary.
- Adjust the infusion rate as required to maintain desired heart rate and blood pressure. Refer to Maximum Recommended Doses below.
- Administer 500 mcg per kg as a bolus dose over 1 minute followed by a maintenance infusion of 50 mcg per kg per min for 4 minutes.
- Depending on the response obtained, continue dosing as outlined for supraventricular tachycardia. Refer to Maximum Recommended Doses below.
- For the treatment of tachycardia, maintenance infusion dosages greater than 200 mcg per kg per min are not recommended; dosages greater than 200 mcg per kg per min provide little additional heart rate-lowering effect, and the rate of adverse reactions increases.
- For the treatment of hypertension, higher maintenance infusion dosages (250-300 mcg per kg per min) may be required. The safety of doses above 300 mcg per kg per minute has not been studied.
- After patients achieve adequate control of the heart rate and a stable clinical status, transition to alternative antiarrhythmic drugs may be accomplished.
- When transitioning from esmolol to alternative drugs, the physician should carefully consider the labeling instructions of the alternative drug selected and reduce the dosage of esmolol as follows:
- Thirty minutes following the first dose of the alternative drug, reduce the esmolol infusion rate by one-half (50%).
- After administration of the second dose of the alternative drug, monitor the patient’s response and if satisfactory control is maintained for the first hour, discontinue the esmolol infusion.
- Esmolol injection is available in a pre-mixed bag and ready-to-use vial. Esmolol is not compatible with Sodium Bicarbonate (5%) solution (limited stability) or furosemide (precipitation).
- Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.
Premixed Bag
- The medication port is to be used solely for withdrawing an initial bolus from the bag.
- Use aseptic technique when withdrawing the bolus dose.
- Do not add any additional medications to the bag.
Ready-to-Use Vial
- The Ready-to-use Vial may be used to administer a loading dosage by hand-held syringe while the maintenance infusion is being prepared.
- Developed by: AHA/ACC/HRS
- IV bolus of 500 mcg/kg administered over 1 min followed by IV infusion of 50–300 mcg/kg/min[1]
- Dosing Information
- Initial dose of 500 mcg/kg/min over 1 minute, then a titrated infusion to a dose of 50 to 300 mcg/kg/min administered over 4 minutes.[2]
- Dosing Information
- 1 mg/kg bolus followed by 250 mcg/kg/min in association with propofol.[3]
- Dosing Information
- 80 mg IV[4]
- Dosing Information
- 100 mg bolus into the aortic root administered followed by a 10 to 15 mg/min infusion as many times as required.[5]
- Dosing Information
- 10 mg/mL.[6]
- Dosing Information
- Initial dose of 500 mcg/kg administered over 1 minute, then 50 mcg/kg/min and titrated up to a maximum of 200 mcg/kg/min in 50 mcg/kg/min increments every 4 minutes.[7]
- Severe sinus bradycardia: May precipitate or worsen bradycardia resulting in cardiogenic shock and cardiac arrest.
- Heart block greater than first degree: Second- or third-degree atrioventricular block may precipitate or worsen bradycardia resulting in cardiogenic shock and cardiac arrest.
- Sick sinus syndrome: May precipitate or worsen bradycardia resulting in cardiogenic shock and cardiac arrest.
- Decompensated heart failure: May worsen heart failure.
- Cardiogenic shock: May precipitate further cardiovascular collapse and cause cardiac arrest.
- IV administration of cardiodepressant calcium channel blockers (e.g., verapamil) and esmolol in close proximity (i.e., while cardiac effects from the other are still present); fatal cardiac arrests have occurred in patients receiving esmolol and intravenous verapamil.
- Pulmonary hypertension: May precipitate cardiorespiratory compromise.
- Hypersensitivity reactions, including anaphylaxis to esmolol or any of the inactive ingredients of the product (cross-sensitivity between beta blockers is possible).
Hypotension can occur at any dose but is dose-related. Patients with hemodynamic compromise or on interacting medications are at particular risk. Severe reactions may include loss of consciousness, cardiac arrest, and death. For control of ventricular heart rate, maintenance doses greater than 200 mcg per kg per min are not recommended. Monitor patients closely, especially if pretreatment blood pressure is low. In case of an unacceptable drop in blood pressure, reduce or stop esmolol injection. Decrease of dose or termination of infusion reverses hypotension, usually within 30 minutes.
Bradycardia, including sinus pause, heart block, severe bradycardia, and cardiac arrest have occurred with the use of esmolol injection. Patients with first-degree atrioventricular block, sinus node dysfunction, or conduction disorders may be at increased risk. Monitor heart rate and rhythm in patients receiving esmolol.
If severe bradycardia develops, reduce or stop esmolol.
Beta blockers, like esmolol injection, can cause depression of myocardial contractility and may precipitate heart failure and cardiogenic shock. At the first sign or symptom of impending cardiac failure, stop esmolol and start supportive therapy.
Monitor vital signs closely and titrate esmolol slowly in the treatment of patients whose blood pressure is primarily driven by vasoconstriction associated with hypothermia.
Patients with reactive airways disease should, in general, not receive beta blockers. Because of its relative beta1 selectivity and titratability, titrate esmolol to the lowest possible effective dose. In the event of bronchospasm, stop the infusion immediately; a beta2 stimulating agent may be administered with appropriate monitoring of ventricular rates.
In patients with hypoglycemia, or diabetic patients (especially those with labile diabetes) who are receiving insulin or other hypoglycemic agents, beta blockers may mask tachycardia occurring with hypoglycemia, but other manifestations such as dizziness and sweating may not be masked.
Concomitant use of beta blockers and antidiabetic agents can enhance the effect of antidiabetic agents (blood glucose–lowering).
Infusion site reactions have occurred with the use of esmolol injection. They include irritation, inflammation, and severe reactions (thrombophlebitis, necrosis, and blistering), in particular when associated with extravasation. Avoid infusions into small veins or through a butterfly catheter.
If a local infusion site reaction develops, use an alternative infusion site and avoid extravasation.
Beta blockers may exacerbate anginal attacks in patients with Prinzmetal’s angina because of unopposed alpha receptor–mediated coronary artery vasoconstriction. Do not use nonselective beta blockers.
If esmolol is used in the setting of pheochromocytoma, give it in combination with an alpha-blocker, and only after the alpha-blocker has been initiated. Administration of beta-blockers alone in the setting of pheochromocytoma has been associated with a paradoxical increase in blood pressure from the attenuation of beta-mediated vasodilation in skeletal muscle.
In hypovolemic patients, esmolol injection can attenuate reflex tachycardia and increase the risk of hypotension.
In patients with peripheral circulatory disorders (including Raynaud’s disease or syndrome, and peripheral occlusive vascular disease), esmolol may aggravate peripheral circulatory disorders.
Severe exacerbations of angina, myocardial infarction, and ventricular arrhythmias have been reported in patients with coronary artery disease upon abrupt discontinuation of beta blocker therapy. Observe patients for signs of myocardial ischemia when discontinuing esmolol.
Heart rate increases moderately above pretreatment levels 30 minutes after esmolol discontinuation.
Beta blockers, including esmolol, have been associated with increases in serum potassium levels and hyperkalemia. The risk is increased in patients with risk factors such as renal impairment. Intravenous administration of beta blockers has been reported to cause potentially life-threatening hyperkalemia in hemodialysis patients. Monitor serum electrolytes during therapy with esmolol.
Beta blockers, including esmolol, have been reported to cause hyperkalemic renal tubular acidosis. Acidosis in general may be associated with reduced cardiac contractility.
Beta-adrenergic blockade may mask certain clinical signs (e.g., tachycardia) of hyperthyroidism. Abrupt withdrawal of beta blockade might precipitate a thyroid storm; therefore, monitor patients for signs of thyrotoxicosis when withdrawing beta blocking therapy.
When using beta blockers, patients at risk of anaphylactic reactions may be more reactive to allergen exposure (accidental, diagnostic, or therapeutic).
Patients using beta blockers may be unresponsive to the usual doses of epinephrine used to treat anaphylactic or anaphylactoid reactions.
- Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.
- The following adverse reaction rates are based on use of esmolol in clinical trials involving 369 patients with supraventricular tachycardia and over 600 intraoperative and postoperative patients enrolled in clinical trials. Most adverse effects observed in controlled clinical trial settings have been mild and transient. The most important and common adverse effect has been hypotension. Deaths have been reported in post-marketing experience occurring during complex clinical states where esmolol was presumably being used simply to control ventricular rate
- Confusional state and agitation (~2%)
- Anxiety, depression and abnormal thinking (<1%)
- Headache (~ 2%)
- Paresthesia, syncope, speech disorder, and lightheadedness (<1%)
- Convulsions (<1%), with one death
- Peripheral ischemia (~1%)
- Pallor and flushing (<1%)
- Vomiting (~1%)
- Dyspepsia, constipation, dry mouth, and abdominal discomfort (<1%)
- Urinary retention (<1%)
## Cardiac Disorders
- Cardiac arrest, Coronary arteriospasm
## Skin and Subcutaneous Tissue Disorders
- Angioedema, Urticaria, Psoriasis
- Digitalis glycosides: Concomitant administration of digoxin and esmolol leads to an approximate 10% to 20% increase of digoxin blood levels at some time points. Digoxin does not affect esmolol pharmacokinetics. Both digoxin and beta blockers slow atrioventricular conduction and decrease the heart rate. Concomitant use increases the risk of bradycardia.
- Anticholinesterases: esmolol prolonged the duration of succinylcholine-induced neuromuscular blockade and moderately prolonged clinical duration and recovery index of mivacurium.
- Antihypertensive agents clonidine, guanfacine, or moxonidine: Beta blockers also increase the risk of clonidine-, guanfacine-, or moxonidine-withdrawal rebound hypertension. If, during concomitant use of a beta blocker, antihypertensive therapy needs to be interrupted or discontinued, discontinue the beta blocker first, and the discontinuation should be gradual.
- Calcium channel antagonists: In patients with depressed myocardial function, use of esmolol with cardiodepressant calcium channel antagonists (e.g., verapamil) can lead to fatal cardiac arrests.
- Sympathomimetic drugs: Sympathomimetic drugs having beta-adrenergic agonist activity will counteract effects of esmolol.
- Vasoconstrictive and positive inotropic agents: Because of the risk of reducing cardiac contractility in presence of high systemic vascular resistance, do not use esmolol to control tachycardia in patients receiving drugs that are vasoconstrictive and have positive inotropic effects, such as epinephrine, norepinephrine, and dopamine.
- Teratogenicity studies in rats at intravenous dosages of esmolol hydrochloride up to 3000 mcg/kg/min (10 times the maximum human maintenance dosage) for 30 minutes daily produced no evidence of maternal toxicity, embryotoxicity or teratogenicity, while a dosage of 10,000 mcg/kg/min produced maternal toxicity and lethality. In rabbits, intravenous dosages up to 1000 mcg/kg/min for 30 minutes daily produced no evidence of maternal toxicity, embryotoxicity or teratogenicity, while 2500 mcg/kg/min produced minimal maternal toxicity and increased fetal resorptions.
- Monitor patients closely, especially if pretreatment blood pressure is low. In case of an unacceptable drop in blood pressure, reduce or stop esmolol injection. Decrease of dose or termination of infusion reverses hypotension, usually within 30 minutes.
- Monitor heart rate and rhythm in patients receiving esmolol.
- In patients with intraoperative and postoperative tachycardia and/or hypertension monitor vital signs closely and titrate smolol slowly in the treatment of patients whose blood pressure is primarily driven by vasoconstriction associated with hypothermia.
- Monitor serum electrolytes during therapy with esmolol.
- Monitor patients for signs of thyrotoxicosis when withdrawing beta blocking therapy.
- Dextrose (5%) Injection, USP
- Dextrose (5%) in Lactated Ringer’s Injection
- Dextrose (5%) in Ringer’s Injection
- Dextrose (5%) and Sodium Chloride (0.45%) Injection, USP
- Dextrose (5%) and Sodium Chloride (0.9%) Injection, USP
- Lactated Ringer’s Injection, USP
- Potassium Chloride (40 mEq/liter) in Dextrose (5%) Injection, USP
- Sodium Chloride (0.45%) Injection, USP
- Sodium Chloride (0.9%) Injection, USP
Overdoses of esmolol can cause cardiac and central nervous system effects. These effects may precipitate severe signs, symptoms, sequelae, and complications (for example, severe cardiac and respiratory failure, including shock and coma), and may be fatal. Continuous monitoring of the patient is required.
Cardiac effects
- Bradycardia,atrioventricular block (1st -, 2nd -, 3rd degree), junctional rhythms, intraventricular conduction delays, decreased cardiac contractility,hypotension, cardiac failure (including cardiogenic shock), cardiac arrest/asystole, and pulseless electrical activity.
Central nervous system
- Respiratory depression,seizures, sleep and mood disturbances, fatigue, lethargy, and coma.
- In addition, bronchospasm, mesenteric ischemia, peripheral cyanosis, hyperkalemia, and hypoglycemia (especially in children) may occur.
- Because of its approximately 9-minute elimination half-life, the first step in the management of toxicity should be to discontinue the esmolol infusion. Then, based on the observed clinical effects, consider the following general measures.
- Consider intravenous administration of atropine or another anticholinergic drug or cardiac pacing.
- Consider intravenous administration of a diuretic or digitalis glycoside. In shock resulting from inadequate cardiac contractility, consider intravenous administration of dopamine, dobutamine, isoproterenol, or inamrinone. Glucagon has been reported to be useful.
- Consider intravenous administration of fluids or vasopressor agents such as dopamine or norepinephrine.
- Consider intravenous administration of a beta 2 stimulating agent or a theophylline derivative.
- Massive accidental overdoses of esmolol have resulted from dilution errors. The use of esmolol premixed injection may reduce the potential for dilution errors. Some of these overdoses have been fatal while others resulted in permanent disability. Bolus doses in the range of 625 mg to 2.5 g (12.5-50 mg/kg) have been fatal. Patients have recovered completely from overdoses as high as 1.75 g given over one minute or doses of 7.5 g given over one hour for cardiovascular surgery. The patients who survived appear to be those whose circulation could be supported until the effects of esmolol resolved.
Its elimination half-life after intravenous infusion is approximately 9 minutes. esmolol inhibits the beta1 adrenergic receptors located chiefly in cardiac muscle, but this preferential effect is not absolute and at higher doses it begins to inhibit beta2 adrenergic receptors located chiefly in the bronchial and vascular musculature.
(±)-Methyl p-[2-hydroxy-3-(isopropylamino) propoxy] hydrocinnamate hydrochloride and has the following structure:
Esmolol hydrochloride has the empirical formula C16H26NO4Cl and a molecular weight of 331.8. It has one asymmetric center and exists as an enantiomeric pair.
Esmolol hydrochloride is a white to off-white crystalline powder. It is a relatively hydrophilic compound which is very soluble in water and freely soluble in alcohol. Its partition coefficient (octanol/water) at pH 7.0 is 0.42 compared to 17.0 for propranolol.
All esmolol presentations are clear, colorless to light yellow, sterile, nonpyrogenic, iso-osmotic solutions of esmolol hydrochloride in sodium chloride. The formulations for esmolol premixed injection, esmolol double strength injection, and esmolol injection are described in the table below:
The calculated osmolarity of esmolol premixed injection and esmolol double strength injection is 312 mOsmol/L. The 250 mL and 100 mL bags are non-latex, non-PVC INTRAVIA bags with dual PVC ports. The INTRAVIA bags are manufactured from a specially designed multilayer plastic (PL 2408). Solutions in contact with the plastic container leach out certain chemical compounds from the plastic in very small amounts; however, biological testing was supportive of the safety of the plastic container materials.
In human electrophysiology studies, esmolol produced effects typical of a beta blocker: a decrease in the heart rate, increase in sinus cycle length, prolongation of the sinus node recovery time, prolongation of the AH interval during normal sinus rhythm and during atrial pacing, and an increase in antegrade Wenckebach cycle length.
In patients undergoing radionuclide angiography, esmolol, at dosages of 200 mcg/kg/min, produced reductions in heart rate, systolic blood pressure, rate pressure product, left and right ventricular ejection fraction and cardiac index at rest, which were similar in magnitude to those produced by intravenous propranolol (4 mg). During exercise, esmolol produced reductions in heart rate, rate pressure product and cardiac index which were also similar to those produced by propranolol, but esmolol produced a significantly larger fall in systolic blood pressure. In patients undergoing cardiac catheterization, the maximum therapeutic dose of 300 mcg/kg/min of esmolol produced similar effects and, in addition, there were small, clinically insignificant increases in the left ventricular end diastolic pressure and pulmonary capillary wedge pressure. At 30 minutes after the discontinuation of esmolol infusion, all of the hemodynamic parameters had returned to pretreatment levels.
The relative cardioselectivity of esmolol was demonstrated in 10 mildly asthmatic patients. Infusions of esmolol 100, 200 and 300 mcg/kg/min produced no significant increases in specific airway resistance compared to placebo. At 300 mcg/kg/min, esmolol produced slightly enhanced bronchomotor sensitivity to dry air stimulus. These effects were not clinically significant, and esmolol was well tolerated by all patients. Six of the patients also received intravenous propranolol, and at a dosage of 1 mg, two experienced significant, symptomatic bronchospasm requiring bronchodilator treatment. One otherpropranolol-treated patient also experienced dry air-induced bronchospasm. No adverse pulmonary effects were observed in patients with COPD who received therapeutic dosages of esmolol for treatment of supraventricular tachycardia (51 patients) or in perioperative settings (32 patients).
Using an appropriate loading dose, steady-state blood levels of esmolol for dosages from 50-300 mcg/kg/min are obtained within five minutes. Steady-state is reached in about 30 minutes without the loading dose. Steady-state blood levels of esmolol increase linearly over this dosage range and elimination kinetics are dose-independent over this range. Steady-state blood levels are maintained during infusion but decrease rapidly after termination of the infusion. Because of its short half-life, blood levels of esmolol can be rapidly altered by increasing or decreasing the infusion rate and rapidly eliminated by discontinuing the infusion.
Consistent with the high rate of blood-based metabolism of esmolol, less than 2% of the drug is excreted unchanged in the urine. Within 24 hours of the end of infusion, the acid metabolite of esmolol in urine accounts for approximately 73-88% of the dosage.
Metabolism of esmolol results in the formation of the corresponding free acid and methanol. The acid metabolite has been shown in animals to have negligible activity and in normal volunteers its blood levels do not correspond to the level of beta blockade. The acid metabolite has an elimination half-life of about 3.7 hours and is excreted in the urine with a clearance approximately equivalent to the glomerular filtration rate. After a 4 hour maintenance infusion of 150 mcg/kg, the plasma concentrations of esmolol are similar in subjects with normal renal function and in patients with ESRD on dialysis. The half-life of the acid metabolite of esmolol, which is primarily excreted unchanged by the kidney, is increased about 12-fold to 48 hours in patients with ESRD. The peak concentrations of the acid metabolite are doubled in ESRD.
Methanol blood levels, monitored in subjects receiving esmolol for up to 6 hours at 300 mcg/kg/min and 24 hours at 150 mcg/kg/min, approximated endogenous levels and were less than 2% of levels usually associated with methanol toxicity.
Esmolol has been shown to be 55% bound to human plasma protein, while the acid metabolite is only 10% bound.
In two multicenter, randomized, double-blind, controlled comparisons of esmolol injection with placebo and propranolol, maintenance doses of 50 to 300 mcg/kg/min of esmolol were found to be more effective than placebo and about as effective as propranolol, 3-6 mg given by bolus injections, in the treatment of supraventricular tachycardia, principally atrial fibrillation and atrial flutter. The majority of these patients developed their arrhythmias postoperatively. About 60-70% of the patients treated with esmolol developed either a 20% reduction in heart rate, a decrease in heart rate to less than 100 bpm, or, rarely, conversion to normal sinus rhythm and about 95% of these patients did so at a dosage of 200 mcg/kg/min or less. The average effective dosage of esmolol was approximately 100 mcg/kg/min in the two studies. Other multicenter baseline-controlled studies gave similar results. In the comparison with propranolol, about 50% of patients in both the esmolol and propranolol groups were on concomitant digoxin. Response rates were slightly higher with both beta blockers in the digoxin-treated patients.
In all studies significant decreases of blood pressure occurred in 20-50% of patients, identified either as adverse reaction reports by investigators, or by observation of systolic pressure less than 90 mmHg or diastolic pressure less than 50 mmHg. The hypotension was symptomatic (mainly hyperhidrosis or dizziness) in about 12% of patients, and therapy was discontinued in about 11% of patients, about half of whom were symptomatic. Hypotension was more common with esmolol (53%) than with propranolol (17%). The hypotension was rapidly reversible with decreased infusion rate or after discontinuation of therapy with esmolol. For both esmolol and propranolol, hypotension was reported less frequently in patients receiving concomitant digoxin.
NDC 10019-055-61, 2500 mg / 250 mL (10 mg/mL) Ready-to-use INTRAVIA Bags
- BREVIBLOC DOUBLE STRENGTH PREMIXED Injection
NDC 10019-075-87, 2000 mg / 100 mL (20 mg/mL) Ready-to-use INTRAVIA Bags
- BREVIBLOC Injection
NDC 10019-115-01, 100 mg / 10 mL (10 mg/mL) Ready-to-use Vials, Package of 25
- Each bag contains no preservative. Once drug has been withdrawn from ready-to-use bag, the bag should be used within 24 hours, with any unused portion discarded.
- Do not use plastic containers in series connections. Such use could result in an embolism due to residual air being drawn from the primary container before administration of the fluid from the secondary container is completed.
- Do not remove unit from overwrap until ready to use. Do not use if overwrap has been previously opened or damaged. The overwrap is a moisture barrier. The inner bag maintains sterility of the solution. Tear overwrap at notch and remove premixed bag. Some opacity of the plastic due to moisture absorption during the sterilization process may be observed. This is normal and does not affect the solution quality or safety. The opacity will diminish gradually.
- Check for minute leaks by squeezing the inner bag firmly. If leaks are found, discard solution, as sterility may be impaired. Do not use unless the solution is clear (colorless to light yellow) and the seal is intact.
- The most common adverse reactions are symptomatic hypotension (hyperhidrosis, dizziness), and asymptomatic hypotension.
- Esmolol HCl
- ↑ January CT, Wann LS, Alpert JS, Calkins H, Cleveland JC, Cigarroa JE; et al. (2014). "2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society". J Am Coll Cardiol. doi:10.1016/j.jacc.2014.03.022. PMID 24685669.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link) .mw-parser-output cite.citation{font-style:inherit}.mw-parser-output q{quotes:"\"""\"""'""'"}.mw-parser-output code.cs1-code{color:inherit;background:inherit;border:inherit;padding:inherit}.mw-parser-output .cs1-lock-free a{background:url("https://upload.wikimedia.org/wikipedia/commons/thumb/6/65/Lock-green.svg/9px-Lock-green.svg.png")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-limited a,.mw-parser-output .cs1-lock-registration a{background:url("https://upload.wikimedia.org/wikipedia/commons/thumb/d/d6/Lock-gray-alt-2.svg/9px-Lock-gray-alt-2.svg.png")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-subscription a{background:url("https://upload.wikimedia.org/wikipedia/commons/thumb/a/aa/Lock-red-alt-2.svg/9px-Lock-red-alt-2.svg.png")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration{color:#555}.mw-parser-output .cs1-subscription span,.mw-parser-output .cs1-registration span{border-bottom:1px dotted;cursor:help}.mw-parser-output .cs1-hidden-error{display:none;font-size:100%}.mw-parser-output .cs1-visible-error{display:none;font-size:100%}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration,.mw-parser-output .cs1-format{font-size:95%}.mw-parser-output .cs1-kern-left,.mw-parser-output .cs1-kern-wl-left{padding-left:0.2em}.mw-parser-output .cs1-kern-right,.mw-parser-output .cs1-kern-wl-right{padding-right:0.2em}
- ↑ Mooss AN, Hilleman DE, Mohiuddin SM, Hunter CB (1994). "Safety of esmolol in patients with acute myocardial infarction treated with thrombolytic therapy who had relative contraindications to beta-blocker therapy". Ann Pharmacother. 28 (6): 701–3. PMID 7919552.CS1 maint: Multiple names: authors list (link)
- ↑ Johansen JW, Flaishon R, Sebel PS (1997). "Esmolol reduces anesthetic requirement for skin incision during propofol/nitrous oxide/morphine anesthesia". Anesthesiology. 86 (2): 364–71. PMID 9054254.CS1 maint: Multiple names: authors list (link)
- ↑ van den Broek WW, Leentjens AF, Mulder PG, Kusuma A, Bruijn JA (1999). "Low-dose esmolol bolus reduces seizure duration during electroconvulsive therapy: a double-blind, placebo-controlled study". Br J Anaesth. 83 (2): 271–4. PMID 10618942.CS1 maint: Multiple names: authors list (link)
- ↑ Mehlhorn U, Sauer H, Kuhn-Régnier F, Südkamp M, Dhein S, Eberhardt F; et al. (1999). "Myocardial beta-blockade as an alternative to cardioplegic arrest during coronary artery surgery". Cardiovasc Surg. 7 (5): 549–57. PMID 10499899.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
- ↑ Zakowski M, Kaufman B, Berguson P, Tissot M, Yarmush L, Turndorf H (1989). "Esmolol use during resection of pheochromocytoma: report of three cases". Anesthesiology. 70 (5): 875–7. PMID 2566290.CS1 maint: Multiple names: authors list (link)
- ↑ Duggal J, Singh S, Kuchinic P, Butler P, Arora R (2006). "Utility of esmolol in thyroid crisis". Can J Clin Pharmacol. 13 (3): e292–5. PMID 17127774.CS1 maint: Multiple names: authors list (link) | https://www.wikidoc.org/index.php/Brevibloc | |
e515fd1548c57b7a732b83bf91008e774552241f | wikidoc | Bromide | Bromide
# Overview
A bromide is a chemical compound containing a bromide ion or ligand. This is a bromine atom with an ionic charge of −1 (Br−); for example, in caesium bromide, caesium cations (Cs+) are electrically attracted to bromide anions (Br−) to form the electrically neutral ionic compound CsBr. The term "bromide" can also refer to a bromine atom with an oxidation number of −1 in covalent compounds such as sulfur dibromide (SBr2).
# Natural occurrence
Bromide is present in typical seawater (35 PSU) with a concentration of around 65 mg/L, which is around 0.2% of all dissolved salts. Seafoods and deep sea plants generally have high levels of bromide, while foods derived from land have variable amounts.
# Chemistry
One can test for a bromide ion by adding excess dilute HNO3 followed by dilute aqueous AgNO3 solution. The formation of creamy silver bromide precipitate confirms the existence of bromides.
# Medical uses
Bromide compounds, especially potassium bromide, were frequently used as sedatives in the 19th and early 20th century. Their use in over-the-counter sedatives and headache remedies (such as Bromo-Seltzer) in the United States extended to 1975, when bromides were withdrawn as ingredients, due to chronic toxicity.
This use gave the word "bromide" its colloquial connotation of a boring cliché, a bit of conventional wisdom overused as a calming phrase, or verbal sedative.
The bromide ion is antiepileptic, and bromide salts are still used as such, particularly in veterinary medicine. Bromide ion is excreted by the kidneys. The half-life of bromide in the human body (12 days) is long compared with many pharmaceuticals, making dosing difficult to adjust (a new dose may require several months to reach equilibrium). Bromide ion concentrations in the cerebrospinal fluid are about 30% of those in blood, and are strongly influenced by the body's chloride intake and metabolism.
Since bromide is still used in veterinary medicine (particularly to treat seizures in dogs) in the United States, veterinary diagnostic labs can routinely measure blood bromide levels. However, this is not a conventional test in human medicine in the U.S., since there are no FDA-approved uses for bromide, and (as noted) it is no longer available in over-the-counter sedatives. Therapeutic bromide levels are measured in European countries like Germany, where bromide is still used therapeutically in human epilepsy.
Chronic toxicity from bromide can result in bromism, a syndrome with multiple neurological symptoms. Bromide toxicity can also cause a type of skin eruption. See potassium bromide.
Lithium bromide was used as a sedative beginning in the early 1900s, but it fell into disfavor in the 1940s, possibly due to the rising popularity of safer and more efficient sedatives (specifically, barbiturates) and when some heart patients died after using a salt substitute (see lithium chloride). Like lithium carbonate and lithium chloride it was used as treatment for bipolar disorder.
It has been said that during World War I, British soldiers were given bromide to curb their sexual urges, although this is not well supported by documentation, and has been disputed as an urban myth, as the sedative effects of bromide would have hampered military performance. Lord Dunsany mentions a soldier being given bromide as a sedative for nervous exhaustion and overwork in his play "Fame and the Poet"(1919).
# In biology
Recently, bromine (as bromide) was shown to be an essential cofactor for the peroxidasin catalyzed formation of sulfilimine crosslinks in collagen IV. Since this is a post-translational modification that occurs in all animals, bromine is therefore an essential trace element for humans.
Bromide is needed by eosinophils (white blood cells of the granulocyte class, specialized for dealing with multi-cellular parasites), which use it to generate antiparasitic brominating compounds such as hypobromite, by the action of eosinophil peroxidase, a haloperoxidase enzyme which is able to use chloride, but preferentially uses bromide when available. Other than its role in collagen IV production and its facultative use in eosinophils by the body, bromide is not known in other cases necessary for animal life, as its functions may generally be replaced (though in some cases not as well) by chloride. Land plants do not use bromide.
Bromide salts are also sometimes used in hot tubs and spas as mild germicidal agents, using the action of an added oxidizing agent to generate in situ hypobromite, in a similar fashion to the peroxidase in eosinophils.
Bromide is perhaps a minor necessary nutrient for collagen IV-producing animals in the sea. However, a few sea animals, such as Murex snails, use bromide to make organic compounds. Bromide ion is also heavily concentrated by some species of ocean algae, which construct methyl bromide and a great number of bromoorganic compounds with it, using the unusual enzymes called vanadium bromoperoxidases to do these reactions.
The average concentration of bromide in human blood in Queensland, Australia is 5.3±1.4 mg/L and varies with age and gender. Much higher levels may indicate exposure to brominated chemicals (e.g. methyl bromide). However, since bromide occurs in relatively high concentration in seawater and many types of seafood, bromide concentrations in the blood are heavily influenced by seafood contributions to the diet. | Bromide
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
# Overview
A bromide is a chemical compound containing a bromide ion or ligand. This is a bromine atom with an ionic charge of −1 (Br−); for example, in caesium bromide, caesium cations (Cs+) are electrically attracted to bromide anions (Br−) to form the electrically neutral ionic compound CsBr. The term "bromide" can also refer to a bromine atom with an oxidation number of −1 in covalent compounds such as sulfur dibromide (SBr2).
# Natural occurrence
Bromide is present in typical seawater (35 PSU) with a concentration of around 65 mg/L, which is around 0.2% of all dissolved salts. Seafoods and deep sea plants generally have high levels of bromide, while foods derived from land have variable amounts.
# Chemistry
One can test for a bromide ion by adding excess dilute HNO3 followed by dilute aqueous AgNO3 solution. The formation of creamy silver bromide precipitate confirms the existence of bromides.
# Medical uses
Bromide compounds, especially potassium bromide, were frequently used as sedatives in the 19th and early 20th century. Their use in over-the-counter sedatives and headache remedies (such as Bromo-Seltzer) in the United States extended to 1975, when bromides were withdrawn as ingredients, due to chronic toxicity.[2]
This use gave the word "bromide" its colloquial connotation of a boring cliché, a bit of conventional wisdom overused as a calming phrase, or verbal sedative.
The bromide ion is antiepileptic, and bromide salts are still used as such, particularly in veterinary medicine. Bromide ion is excreted by the kidneys. The half-life of bromide in the human body (12 days) is long compared with many pharmaceuticals, making dosing difficult to adjust (a new dose may require several months to reach equilibrium). Bromide ion concentrations in the cerebrospinal fluid are about 30% of those in blood, and are strongly influenced by the body's chloride intake and metabolism.[3]
Since bromide is still used in veterinary medicine (particularly to treat seizures in dogs) in the United States, veterinary diagnostic labs can routinely measure blood bromide levels. However, this is not a conventional test in human medicine in the U.S., since there are no FDA-approved uses for bromide, and (as noted) it is no longer available in over-the-counter sedatives. Therapeutic bromide levels are measured in European countries like Germany, where bromide is still used therapeutically in human epilepsy.
Chronic toxicity from bromide can result in bromism, a syndrome with multiple neurological symptoms. Bromide toxicity can also cause a type of skin eruption. See potassium bromide.
Lithium bromide was used as a sedative beginning in the early 1900s, but it fell into disfavor in the 1940s, possibly due to the rising popularity of safer and more efficient sedatives (specifically, barbiturates) and when some heart patients died after using a salt substitute (see lithium chloride).[4] Like lithium carbonate and lithium chloride it was used as treatment for bipolar disorder.
It has been said that during World War I, British soldiers were given bromide to curb their sexual urges,[5] although this is not well supported by documentation, and has been disputed as an urban myth, as the sedative effects of bromide would have hampered military performance. Lord Dunsany mentions a soldier being given bromide as a sedative for nervous exhaustion and overwork in his play "Fame and the Poet"(1919).
# In biology
Recently, bromine (as bromide) was shown to be an essential cofactor for the peroxidasin catalyzed formation of sulfilimine crosslinks in collagen IV. Since this is a post-translational modification that occurs in all animals, bromine is therefore an essential trace element for humans.[6]
Bromide is needed by eosinophils (white blood cells of the granulocyte class, specialized for dealing with multi-cellular parasites), which use it to generate antiparasitic brominating compounds such as hypobromite, by the action of eosinophil peroxidase, a haloperoxidase enzyme which is able to use chloride, but preferentially uses bromide when available.[7] Other than its role in collagen IV production and its facultative use in eosinophils by the body, bromide is not known in other cases necessary for animal life, as its functions may generally be replaced (though in some cases not as well) by chloride. Land plants do not use bromide.
Bromide salts are also sometimes used in hot tubs and spas as mild germicidal agents, using the action of an added oxidizing agent to generate in situ hypobromite, in a similar fashion to the peroxidase in eosinophils.
Bromide is perhaps a minor necessary nutrient for collagen IV-producing animals in the sea. However, a few sea animals, such as Murex snails, use bromide to make organic compounds. Bromide ion is also heavily concentrated by some species of ocean algae, which construct methyl bromide and a great number of bromoorganic compounds with it, using the unusual enzymes called vanadium bromoperoxidases to do these reactions.
The average concentration of bromide in human blood in Queensland, Australia is 5.3±1.4 mg/L and varies with age and gender.[8] Much higher levels may indicate exposure to brominated chemicals (e.g. methyl bromide). However, since bromide occurs in relatively high concentration in seawater and many types of seafood, bromide concentrations in the blood are heavily influenced by seafood contributions to the diet. | https://www.wikidoc.org/index.php/Bromide | |
cdea8ecc150eda7794bbac3a8cb5f21eb801dbe1 | wikidoc | Eyebrow | Eyebrow
The eyebrow is an area of coarse skin hairs above the eye that follows the shape of the brow ridges.
# Functions
The main function of the eyebrows is to prevent moisture, mostly salty sweat and rain, from flowing into the eye, an organ critical to sight. The typical curved shape of the eyebrow (with a slant on the side) and the direction in which eyebrow hairs are pointed, make sure that moisture has a tendency to flow sideways around the eyes, along the side of the head and along the nose. The slightly protruding brow ridges of modern humans could also still play a supporting role in this process. Together with the eyebrows, the brow ridges also shade the eyes from sunlight.
Eyebrows also prevent debris such as dandruff and other small objects from falling into the eyes, as well as providing a more sensitive sense for detecting objects being near the eye, like small insects.
Eyebrows also have an important facilitative function in communication, strengthening expressions like surprise or anger. In African cultures, raising and lowering the eyebrows is used as a confirmation sign (the equivalent of nodding).
# Eyebrow modification
It is common for people to pluck their eyebrows to maintain a clean and fashionable appearance with the use of tweezers and waxing. Threading eyebrows has also become a popular method because it does not pull at the skin. All of these methods can be painful for some seconds or minutes due to the sensitivity of the area around the eye but often this pain decreases over time as the individual becomes used to the sensation.
Some people also choose to pierce their eyebrow. | Eyebrow
Template:Infobox Anatomy
The eyebrow is an area of coarse skin hairs above the eye that follows the shape of the brow ridges.
# Functions
The main function of the eyebrows is to prevent moisture, mostly salty sweat and rain, from flowing into the eye, an organ critical to sight. The typical curved shape of the eyebrow (with a slant on the side) and the direction in which eyebrow hairs are pointed, make sure that moisture has a tendency to flow sideways around the eyes, along the side of the head and along the nose. The slightly protruding brow ridges of modern humans could also still play a supporting role in this process. Together with the eyebrows, the brow ridges also shade the eyes from sunlight.
Eyebrows also prevent debris such as dandruff and other small objects from falling into the eyes, as well as providing a more sensitive sense for detecting objects being near the eye, like small insects.
Eyebrows also have an important facilitative function in communication, strengthening expressions like surprise or anger. In African cultures, raising and lowering the eyebrows is used as a confirmation sign (the equivalent of nodding).
# Eyebrow modification
It is common for people to pluck their eyebrows to maintain a clean and fashionable appearance with the use of tweezers and waxing. Threading eyebrows has also become a popular method because it does not pull at the skin. All of these methods can be painful for some seconds or minutes due to the sensitivity of the area around the eye but often this pain decreases over time as the individual becomes used to the sensation.
Some people also choose to pierce their eyebrow. | https://www.wikidoc.org/index.php/Brow | |
5b326095ddc3aeded804d2218244cf1c8d703b1b | wikidoc | Bruxism | Bruxism
# Overview
Bruxism is defined as repeated involuntary grinding and clenching of teeth which can occur either diurnal or nocturnally. In 1907, Marie Pielkiewics coined the French term 'La Bruxomanie" for bruxism. Bruxism can be classified into awake bruxism and sleep bruxism based on the physiological sleep status of the individual. The etiology of bruxism can be categorized into three groups:psychosocial factors, peripheral factors, and pathophysiological factors. Multifactorial etiology causes involving brain neurotransmitters or basal ganglia. Bruxism affects men and women equally. Factors associated with an increased risk of bruxism include obstructive sleep apnea, alcohol abuse, caffeine intake, smoking, and anxiety. The symptoms of bruxism usually develop in the first decade of life, and start with the appearance of the first primary upper and lower anterior teeth. Common complications of bruxism are tooth wear, and tooth hypersensitivity. Bruxism is primarily diagnosed based on the clinical presentation. History of complaints of disturbance from the clicking or grating sound by the accompanied partners. The most common symptoms of bruxism include involuntary rhythmic contractions of the masticator muscles during sleep. Removal of any offending agent responsible for bruxism is the primary step in the management. Surgery is the mainstay of treatment in the management of bruxism.
# Historical Perspective
- In 1907, Marie Pielkiewics coined the French term 'La Bruxomanie" for bruxism.
- In 1931, Frohman first coined the English term bruxism.
# Classification
Bruxism can be classified into awake bruxism and sleep bruxism based on the physiological sleep status of the individual.
# Causes
The etiology of bruxism can be categorized into three groups: psychosocial factors, peripheral factors, and pathophysiological factors.
# Pathophysiology
- Bruxism is caused by the activation of reflexive chewing activity
- Chewing is a neuromuscular activity that is controlled by the reflex nerve pathways.
- During sleep, the reflex part is active while the higher control is inactive, resulting in bruxism.
- As stated, bruxism is considered to have multifactorial etiology. Multifactorial etiology causes involving brain neurotransmitters or basal ganglia.
- Pathophysiological Factors
As bruxism often occurs during sleep, the physiology of sleep has been studied extensively, especially the ‘arousal response’, in search of possible causes of a disorder.
Arousal response is a sudden change in the depth of the sleep during which the individual either arrives in the lighter sleep stage or actually wakes up.
Such a response is accompanied by gross body movements, increased heart rate, respiratory changes, and increased muscle activity.
It is derived that disturbances in the central neurotransmitter system may be involved in the etiology of bruxism.
It is hypothesized that the direct and indirect pathways of the basal ganglion, a group of five subcortical nuclei that are involved in the coordination of movements, is disturbed in bruxer.
The direct output pathway goes directly from the stratum to the thalamus from where afferent signals project to the cerebral cortex. The indirect pathway, on the other hand, passes by several other nuclei before reaching it to the thalamus.
If there is an imbalance between the pathways, movement disorder results like Parkinson’s disease.
The imbalance occurs with the disturbances in the dopamine-mediated transmission of an action potential. In the case of bruxism there may be an imbalance in both pathways.
Acute use of dopamine precursors like L-dopa inhibits bruxism activity and chronic long-term use of l-dopa results in increased bruxism activity. SSRTs (serotonin reuptake inhibitors), which exert an indirect influence on the dopaminergic system, may cause bruxism after long-term use.
Amphetamine, which increases the dopamine concentration by facilitating its release has been observed to increase bruxism.
Nicotine stimulates central dopaminergic activities, which might explain the finding that cigarette smokers report bruxism two times more than the nonsmokers.
- As bruxism often occurs during sleep, the physiology of sleep has been studied extensively, especially the ‘arousal response’, in search of possible causes of a disorder.
- Arousal response is a sudden change in the depth of the sleep during which the individual either arrives in the lighter sleep stage or actually wakes up.
- Such a response is accompanied by gross body movements, increased heart rate, respiratory changes, and increased muscle activity.
- It is derived that disturbances in the central neurotransmitter system may be involved in the etiology of bruxism.
- It is hypothesized that the direct and indirect pathways of the basal ganglion, a group of five subcortical nuclei that are involved in the coordination of movements, is disturbed in bruxer.
- The direct output pathway goes directly from the stratum to the thalamus from where afferent signals project to the cerebral cortex. The indirect pathway, on the other hand, passes by several other nuclei before reaching it to the thalamus.
- If there is an imbalance between the pathways, movement disorder results like Parkinson’s disease.
- The imbalance occurs with the disturbances in the dopamine-mediated transmission of an action potential. In the case of bruxism there may be an imbalance in both pathways.
- Acute use of dopamine precursors like L-dopa inhibits bruxism activity and chronic long-term use of l-dopa results in increased bruxism activity. SSRTs (serotonin reuptake inhibitors), which exert an indirect influence on the dopaminergic system, may cause bruxism after long-term use.
- Amphetamine, which increases the dopamine concentration by facilitating its release has been observed to increase bruxism.
- Nicotine stimulates central dopaminergic activities, which might explain the finding that cigarette smokers report bruxism two times more than the nonsmokers.
- Psychosocial Factors
There is no proper description of conclusive nature of psychological factors role in bruxism because of the absence of large scale longitudinal trials.
- There is no proper description of conclusive nature of psychological factors role in bruxism because of the absence of large scale longitudinal trials.
## Associated Factors
- Disturbed sleep pattern/other sleep disorders (obstructive sleep apnea, snoring, moderate daytime sleepiness)
- Malocclusion, in which the upper and lower teeth fit together in a dysfunctional way, typically through lateral asymmetry and dysocclusion of the front teeth through premature contact of back teeth.
- Relatively high levels of consumption of caffeinated drinks and foods, such as coffee, colas, and chocolate
- High levels of alcohol consumption
- Smoking
- High levels of anxiety and/or stress
- SSRIs
- Digestive problems
- Hypersensitivity of the dopamine receptors in the brain.
- Consumption of stimulant drugs and medications, such as those of the amphetamine-based family, such as MDMA
- Excessive use of (i.e., frequent redosing and dependency on) GHB and similar GABA-inducing analogues such as Phenibut
- Disorders such as Huntington's and Parkinson's diseases
# Epidemiology and Demographics
Bruxism often occurs during sleep and can even occur during short naps. Bruxism is one of the most common sleep disorders: 30 to 40 million Americans grind their teeth during sleep.
### Gender
- Bruxism affects men and women equally.
### Age
- Bruxism commonly affects individuals younger than 6 years of age and its incidence declines as age increases.
# Screening
There is insufficient evidence to recommend routine screening for bruxism.
# Risk Factors
Factors associated with an increased risk of bruxism include:
- Obstructive sleep apnea
- Alcohol abuse
- Caffeine intake
- Smoking
- Anxiety
# Natural History, Complications and Prognosis
## Natural History
- The symptoms of bruxism, usually develop in the first decade of life, and start with symptoms such as appearance of the first primary upper and lower anterior teeth.
- The symptoms of bruxism typically develop in childhood and may persist into adult due to presence of other risk factors.
- Usually bruxism follows a benign course.
- If left untreated, bruxism can lead to hypertrophy of masseter muscle accompanied by tenderness of TMJ, which manifests as otalgia.
## Complications
Common complications of bruxism are:
- Tooth wear
- Tooth hypersensitivity
- Tooth mobility
- Pain in the temporomandibular joint (TMJ) or jaw musculature
- Temporal headache,
- Poor sleep
- Signs of this parafunctional habit
Indentation on the tongue
Presence of linea alba along the biting plane of the buccal mucosa
Gingival recessions
- Indentation on the tongue
- Presence of linea alba along the biting plane of the buccal mucosa
- Gingival recessions
# Diagnosis
## Diagnostic study of choice
Bruxism is primarily diagnosed based on the clinical presentation.
- History of tooth grinding during sleep
- Confirmation by parents or bed partners.
## History
- History of complaints of disturbance from the clicking or grating sound by the accompanied partners.
## Symptoms
The most common symptoms of bruxism include:
- Involuntary rhythmic contractions of the masticator muscles during sleep.
- Secondary symptoms may develop due to forceful grinding in some patients which include:
Morning headaches
Jaw pain
Clicking in the temporomandibular joints
- Morning headaches
- Jaw pain
- Clicking in the temporomandibular joints
- Dental deformities may be seen, however not disease specific, and not limited to:
Thermal sensitivity in the teeth
Hypermobility
Need for dental restorations
Tooth wear on tooth surfaces that contact during biting or chewing
Lateral grinding forces in particular can be particularly destructive.
- Thermal sensitivity in the teeth
- Hypermobility
- Need for dental restorations
- Tooth wear on tooth surfaces that contact during biting or chewing
- Lateral grinding forces in particular can be particularly destructive.
- Severe cases of bruxism do present with:
Injury to soft tissues of the mouth
Dental fractures
Difficulty with chewing
Temporomandibular joint pain and dysfunction
Head and neck pain
- Injury to soft tissues of the mouth
- Dental fractures
- Difficulty with chewing
- Temporomandibular joint pain and dysfunction
- Head and neck pain
## Physical Examination
Patients with bruxism usually appear normal.
## Laboratory Findings
There are no diagnostic laboratory findings associated with bruxism.
## Electrocardiogram
There are no ECGfindings associated with bruxism.
## X-ray
There are no x-ray findings associated with bruxism.
## Echocardiography or Ultrasound
There are no echocardiography/ultrasound findings associated with bruxism .
## CT scan
There are no CT scan findings associated with bruxism.
## MRI
There are no MRI findings associated with bruxism.
## Other Imaging Findings
There are no other imaging findings associated with bruxism.
## Other Diagnostic Studies
There are no other diagnostic studies associated with bruxism.
# Treatment
## Medical Therapy
- Removal of any offending agent responsible for bruxism is the primary step in management.
- The wait-and-see approach is recommended in cases with medically induced bruxism, as spontaneous remission is ensured with the cessation of the offending agent.
- Pharmacotherapy mainly concentrated to alleviate symptoms
- Buspirone and Gabapentin are the two recommended medications to manage bruxism
Preferred regimen 1 : Buspirone 15 to 20 mg/day PO q12.
Preferred regimen 2: Gabapentin 100 to 300 mg PO q24
- Preferred regimen 1 : Buspirone 15 to 20 mg/day PO q12.
- Preferred regimen 2: Gabapentin 100 to 300 mg PO q24
## Surgery
Surgery is the mainstay of treatment in the management of bruxism.
### Indications
The treatment of bruxism is indicated when there are any of these possible consequences:
- Mechanical wear of the teeth, which results in loss of occlusal morphology and flattening of the occlusal surfaces
- Hypersensitive teeth
- Loss of periodontal support
- Tooth fractures
- Restorations fractures, usually class I and class II restorations, fracture of crowns, and fixed partial prosthesis
- Restorations or dental implants failure
- Hypertrophy of masticatory muscles
- Tenderness and stiffness in jaw muscles
- When bruxism leads to limited mouth opening
- Temporomandibularpain
- Pain in the preauricular region | Bruxism
For patient information click here
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] ; Associate Editor(s)-in-Chief: Aditya Ganti M.B.B.S. [2]
# Overview
Bruxism is defined as repeated involuntary grinding and clenching of teeth which can occur either diurnal or nocturnally. In 1907, Marie Pielkiewics coined the French term 'La Bruxomanie" for bruxism. Bruxism can be classified into awake bruxism and sleep bruxism based on the physiological sleep status of the individual. The etiology of bruxism can be categorized into three groups:psychosocial factors, peripheral factors, and pathophysiological factors. Multifactorial etiology causes involving brain neurotransmitters or basal ganglia. Bruxism affects men and women equally. Factors associated with an increased risk of bruxism include obstructive sleep apnea, alcohol abuse, caffeine intake, smoking, and anxiety. The symptoms of bruxism usually develop in the first decade of life, and start with the appearance of the first primary upper and lower anterior teeth. Common complications of bruxism are tooth wear, and tooth hypersensitivity. Bruxism is primarily diagnosed based on the clinical presentation. History of complaints of disturbance from the clicking or grating sound by the accompanied partners. The most common symptoms of bruxism include involuntary rhythmic contractions of the masticator muscles during sleep. Removal of any offending agent responsible for bruxism is the primary step in the management. Surgery is the mainstay of treatment in the management of bruxism.
# Historical Perspective
- In 1907, Marie Pielkiewics coined the French term 'La Bruxomanie" for bruxism. [1]
- In 1931, Frohman first coined the English term bruxism.
# Classification
Bruxism can be classified into awake bruxism and sleep bruxism based on the physiological sleep status of the individual.[2][3]
# Causes
The etiology of bruxism can be categorized into three groups: psychosocial factors, peripheral factors, and pathophysiological factors.[3]
# Pathophysiology
- Bruxism is caused by the activation of reflexive chewing activity[4]
- Chewing is a neuromuscular activity that is controlled by the reflex nerve pathways.
- During sleep, the reflex part is active while the higher control is inactive, resulting in bruxism.
- As stated, bruxism is considered to have multifactorial etiology. Multifactorial etiology causes involving brain neurotransmitters or basal ganglia.
- Pathophysiological Factors
As bruxism often occurs during sleep, the physiology of sleep has been studied extensively, especially the ‘arousal response’, in search of possible causes of a disorder.[4]
Arousal response is a sudden change in the depth of the sleep during which the individual either arrives in the lighter sleep stage or actually wakes up.
Such a response is accompanied by gross body movements, increased heart rate, respiratory changes, and increased muscle activity.
It is derived that disturbances in the central neurotransmitter system may be involved in the etiology of bruxism.
It is hypothesized that the direct and indirect pathways of the basal ganglion, a group of five subcortical nuclei that are involved in the coordination of movements, is disturbed in bruxer.
The direct output pathway goes directly from the stratum to the thalamus from where afferent signals project to the cerebral cortex. The indirect pathway, on the other hand, passes by several other nuclei before reaching it to the thalamus.
If there is an imbalance between the pathways, movement disorder results like Parkinson’s disease.
The imbalance occurs with the disturbances in the dopamine-mediated transmission of an action potential. In the case of bruxism there may be an imbalance in both pathways.
Acute use of dopamine precursors like L-dopa inhibits bruxism activity and chronic long-term use of l-dopa results in increased bruxism activity. SSRTs (serotonin reuptake inhibitors), which exert an indirect influence on the dopaminergic system, may cause bruxism after long-term use.
Amphetamine, which increases the dopamine concentration by facilitating its release has been observed to increase bruxism.
Nicotine stimulates central dopaminergic activities, which might explain the finding that cigarette smokers report bruxism two times more than the nonsmokers.
- As bruxism often occurs during sleep, the physiology of sleep has been studied extensively, especially the ‘arousal response’, in search of possible causes of a disorder.[4]
- Arousal response is a sudden change in the depth of the sleep during which the individual either arrives in the lighter sleep stage or actually wakes up.
- Such a response is accompanied by gross body movements, increased heart rate, respiratory changes, and increased muscle activity.
- It is derived that disturbances in the central neurotransmitter system may be involved in the etiology of bruxism.
- It is hypothesized that the direct and indirect pathways of the basal ganglion, a group of five subcortical nuclei that are involved in the coordination of movements, is disturbed in bruxer.
- The direct output pathway goes directly from the stratum to the thalamus from where afferent signals project to the cerebral cortex. The indirect pathway, on the other hand, passes by several other nuclei before reaching it to the thalamus.
- If there is an imbalance between the pathways, movement disorder results like Parkinson’s disease.
- The imbalance occurs with the disturbances in the dopamine-mediated transmission of an action potential. In the case of bruxism there may be an imbalance in both pathways.
- Acute use of dopamine precursors like L-dopa inhibits bruxism activity and chronic long-term use of l-dopa results in increased bruxism activity. SSRTs (serotonin reuptake inhibitors), which exert an indirect influence on the dopaminergic system, may cause bruxism after long-term use.
- Amphetamine, which increases the dopamine concentration by facilitating its release has been observed to increase bruxism.
- Nicotine stimulates central dopaminergic activities, which might explain the finding that cigarette smokers report bruxism two times more than the nonsmokers.
- Psychosocial Factors
There is no proper description of conclusive nature of psychological factors role in bruxism because of the absence of large scale longitudinal trials.
- There is no proper description of conclusive nature of psychological factors role in bruxism because of the absence of large scale longitudinal trials.
## Associated Factors
- Disturbed sleep pattern/other sleep disorders[5][6] (obstructive sleep apnea,[7] snoring,[8] moderate daytime sleepiness[5])
- Malocclusion, in which the upper and lower teeth fit together in a dysfunctional way, typically through lateral asymmetry and dysocclusion of the front teeth through premature contact of back teeth.
- Relatively high levels of consumption of caffeinated drinks and foods, such as coffee, colas, and chocolate[5]
- High levels of alcohol consumption[5]
- Smoking[5]
- High levels of anxiety and/or stress[5]
- SSRIs
- Digestive problems
- Hypersensitivity of the dopamine receptors in the brain.
- Consumption of stimulant drugs and medications, such as those of the amphetamine-based family, such as MDMA[9]
- Excessive use of (i.e., frequent redosing and dependency on) GHB and similar GABA-inducing analogues such as Phenibut [9]
- Disorders such as Huntington's and Parkinson's diseases [10]
# Epidemiology and Demographics
Bruxism often occurs during sleep and can even occur during short naps. Bruxism is one of the most common sleep disorders: 30 to 40 million Americans grind their teeth during sleep.
### Gender
- Bruxism affects men and women equally.
### Age
- Bruxism commonly affects individuals younger than 6 years of age and its incidence declines as age increases.
-
# Screening
There is insufficient evidence to recommend routine screening for bruxism.
# Risk Factors
Factors associated with an increased risk of bruxism include:
- Obstructive sleep apnea
- Alcohol abuse
- Caffeine intake
- Smoking
- Anxiety
# Natural History, Complications and Prognosis
## Natural History
- The symptoms of bruxism, usually develop in the first decade of life, and start with symptoms such as appearance of the first primary upper and lower anterior teeth.
- The symptoms of bruxism typically develop in childhood and may persist into adult due to presence of other risk factors.
- Usually bruxism follows a benign course.
- If left untreated, bruxism can lead to hypertrophy of masseter muscle accompanied by tenderness of TMJ, which manifests as otalgia.
## Complications
Common complications of bruxism are:
- Tooth wear
- Tooth hypersensitivity
- Tooth mobility
- Pain in the temporomandibular joint (TMJ) or jaw musculature
- Temporal headache,
- Poor sleep
- Signs of this parafunctional habit
Indentation on the tongue
Presence of linea alba along the biting plane of the buccal mucosa
Gingival recessions
- Indentation on the tongue
- Presence of linea alba along the biting plane of the buccal mucosa
- Gingival recessions
# Diagnosis
## Diagnostic study of choice
Bruxism is primarily diagnosed based on the clinical presentation.
- History of tooth grinding during sleep
- Confirmation by parents or bed partners.
## History
- History of complaints of disturbance from the clicking or grating sound by the accompanied partners.
## Symptoms
The most common symptoms of bruxism include:[11]
- Involuntary rhythmic contractions of the masticator muscles during sleep.
- Secondary symptoms may develop due to forceful grinding in some patients which include:
Morning headaches
Jaw pain
Clicking in the temporomandibular joints
- Morning headaches
- Jaw pain
- Clicking in the temporomandibular joints
- Dental deformities may be seen, however not disease specific, and not limited to:
Thermal sensitivity in the teeth
Hypermobility
Need for dental restorations
Tooth wear on tooth surfaces that contact during biting or chewing
Lateral grinding forces in particular can be particularly destructive.
- Thermal sensitivity in the teeth
- Hypermobility
- Need for dental restorations
- Tooth wear on tooth surfaces that contact during biting or chewing
- Lateral grinding forces in particular can be particularly destructive.
- Severe cases of bruxism do present with:
Injury to soft tissues of the mouth
Dental fractures
Difficulty with chewing
Temporomandibular joint pain and dysfunction
Head and neck pain
- Injury to soft tissues of the mouth
- Dental fractures
- Difficulty with chewing
- Temporomandibular joint pain and dysfunction
- Head and neck pain
## Physical Examination
Patients with bruxism usually appear normal.
## Laboratory Findings
There are no diagnostic laboratory findings associated with bruxism.
## Electrocardiogram
There are no ECGfindings associated with bruxism.
## X-ray
There are no x-ray findings associated with bruxism.
## Echocardiography or Ultrasound
There are no echocardiography/ultrasound findings associated with bruxism .
## CT scan
There are no CT scan findings associated with bruxism.
## MRI
There are no MRI findings associated with bruxism.
## Other Imaging Findings
There are no other imaging findings associated with bruxism.
## Other Diagnostic Studies
There are no other diagnostic studies associated with bruxism.
# Treatment
## Medical Therapy
- Removal of any offending agent responsible for bruxism is the primary step in management.[11][12][13]
- The wait-and-see approach is recommended in cases with medically induced bruxism, as spontaneous remission is ensured with the cessation of the offending agent.
- Pharmacotherapy mainly concentrated to alleviate symptoms
- Buspirone and Gabapentin are the two recommended medications to manage bruxism
Preferred regimen 1 : Buspirone 15 to 20 mg/day PO q12.
Preferred regimen 2: Gabapentin 100 to 300 mg PO q24
- Preferred regimen 1 : Buspirone 15 to 20 mg/day PO q12.
- Preferred regimen 2: Gabapentin 100 to 300 mg PO q24
## Surgery
Surgery is the mainstay of treatment in the management of bruxism.
### Indications
The treatment of bruxism is indicated when there are any of these possible consequences:[11][12]
- Mechanical wear of the teeth, which results in loss of occlusal morphology and flattening of the occlusal surfaces
- Hypersensitive teeth
- Loss of periodontal support
- Tooth fractures
- Restorations fractures, usually class I and class II restorations, fracture of crowns, and fixed partial prosthesis
- Restorations or dental implants failure
- Hypertrophy of masticatory muscles
- Tenderness and stiffness in jaw muscles
- When bruxism leads to limited mouth opening
- Temporomandibularpain
- Pain in the preauricular region | https://www.wikidoc.org/index.php/Bruxia | |
92d90f9a0da062cad59d5775e777786885ff7e41 | wikidoc | Bufagin | Bufagin
Bufagin is toxic steroid, C24H34O5, found as a component of bufotoxin. It is obtained (in form of marinobufagin) from toad's milk, which refers to secretions from the Cane Toad (Bufo marinus), when it is injured, scared or provoked.
Its effects are similar to poisoning by digitalis, having an effect on the cardiac muscle, causing ventricular fibrillation. It has equally some local anesthetic action. The analgesic effect has also been proven (Wang, Sun et al. 1994), by acting as a Na+/K+-ATPase inhibitor on the binding sites of the cell membrane. The anti-cancer properties in leukemia and melanoma cells, and the inhibition of the proliferation of prostate cancer cells, have also been investigated.
There are several closely related bufagins, such as:
- The very toxic arenobufagin C25H34O6, obtained from the Argentine Toad (Bufo arenarum)
- Cinobufagin, from Chusan Island Toad (Bufo gargarizans)
- Gamabufagin, from the Japanese Toad (Bufo japonicus)
- Quercicobufagin, from Oak Toad (Bufo quercicus)
- Regularobufagin, from the Square-marked Toad (Bufo regularis)
- Vallicepobufagin, from the Gulf Coast Toad (Bufo valliceps)
- Viridibufagin, from the European Green Toad (Bufo viridis)
These bufagins, and especially cinobufagin, have given rise a large number of derivatives, such as desacetylcinobufagin 16-O-β-D-glucoside, 3-epi-desacetylcinobufagin 16-O-β-D-glucoside, 3-oxo-desacetylcinobufagin 16-O-β-D-glucoside and cinobufagin 3-O-β-D-glucoside. | Bufagin
Bufagin is toxic steroid, C24H34O5, found as a component of bufotoxin. It is obtained (in form of marinobufagin) from toad's milk, which refers to secretions from the Cane Toad (Bufo marinus), when it is injured, scared or provoked.
Its effects are similar to poisoning by digitalis, having an effect on the cardiac muscle, causing ventricular fibrillation. It has equally some local anesthetic action. The analgesic effect has also been proven (Wang, Sun et al. 1994), by acting as a Na+/K+-ATPase inhibitor on the binding sites of the cell membrane. The anti-cancer properties in leukemia and melanoma cells, and the inhibition of the proliferation of prostate cancer cells, have also been investigated.
There are several closely related bufagins, such as:
- The very toxic arenobufagin C25H34O6, obtained from the Argentine Toad (Bufo arenarum)
- Cinobufagin, from Chusan Island Toad (Bufo gargarizans)
- Gamabufagin, from the Japanese Toad (Bufo japonicus)
- Quercicobufagin, from Oak Toad (Bufo quercicus)
- Regularobufagin, from the Square-marked Toad (Bufo regularis)
- Vallicepobufagin, from the Gulf Coast Toad (Bufo valliceps)
- Viridibufagin, from the European Green Toad (Bufo viridis)
These bufagins, and especially cinobufagin, have given rise a large number of derivatives, such as desacetylcinobufagin 16-O-β-D-glucoside, 3-epi-desacetylcinobufagin 16-O-β-D-glucoside, 3-oxo-desacetylcinobufagin 16-O-β-D-glucoside and cinobufagin 3-O-β-D-glucoside. | https://www.wikidoc.org/index.php/Bufagin | |
2bcd4e30434f99b2c035d158996466c6b644f921 | wikidoc | Burdock | Burdock
Burdock is any of a group of biennial thistles in the genus Arctium, family Asteraceae. Common Burdock (A. minus) grows wild throughout most of North America, Europe and Asia.
Plants of the genus Arctium have dark green leaves that can grow up to 18" (45 cm) long. They are generally large, coarse and ovate, with the lower ones being heart-shaped. They are woolly underneath. The leafstalks are generally hollow. Arctium species generally flower from July through October.
The prickly heads of these Old World plants are noted for easily catching on to fur and clothing, thus providing an excellent mechanism for seed dispersal. Burrs cause local irritation and can possibly cause intestinal hairballs in pets. However, most animals avoid ingesting these plants.
A large number of species have been placed in genus Arctium at one time or another, but most of them are now classified in the related genus Cousinia. The precise limits between Arctium and Cousinia are hard to define; there is an exact correlation between their molecular phylogeny. The burdocks are sometimes confused with the cockleburs (genus Xanthium) and rhubarb (genus Rheum).
The roots of burdock, among other plants, are eaten by the larva of the Ghost Moth (Hepialus humuli). The plant is used as a food plant by other Lepidoptera including Brown-tail, Coleophora paripennella, Coleophora peribenanderi, The Gothic, Lime-speck Pug and Scalloped Hazel.
The green, above-ground portions may cause contact dermatitis in humans due to the lactones the plant produces.
# Uses
## Food and drink
The taproot of young burdock plants can be harvested and eaten as a root vegetable. While generally out of favor in modern European cuisine, it remains popular in Asia, particularly in Japan where A. lappa (Greater burdock) is called gobō (牛蒡 or ゴボウ). Plants are cultivated for their slender roots, which can grow about 1 meter long and 2 cm across. Burdock root is very crisp and has a sweet, mild, and pungent flavor with a little muddy harshness that can be reduced by soaking julienne/shredded roots in water for five to ten minutes. Immature flower stalks may also be harvested in late spring, before flowers appear; the taste resembles that of artichoke, to which the burdock is related. A popular Japanese dish is kinpira gobō, julienned or shredded burdock root and carrot, braised with soy sauce, sugar, mirin and/or sake, and sesame oil; another is burdock makizushi (sushi filled with pickled burdock root rather than fish; the burdock root is often artificially colored orange to resemble a carrot). In the second half of the 20th century, burdock achieved international recognition for its culinary use due to the increasing popularity of the macrobiotic diet, which advocates its consumption. It also contains a fair amount of gobō dietary fiber (GDF, 6g per 100g), calcium, potassium, amino acids, and is also low calorie. It also contains polyphenols that causes darkened surface and muddy harshness by formation of tannin-iron complexes though the harshness shows excellent harmonization with pork in miso soup (tonjiru) and Japanese-style pilaf (takikomi gohan).
Dandelion and burdock is a soft drink that has long been popular in the United Kingdom. Burdock is believed to be a galactagogue, a substance that increases lactation.
## Traditional medicine
Folk herbalists consider dried burdock to be a diuretic, diaphoretic, and a blood purifying agent. The seeds of A. lappa are used in traditional Chinese medicine, under the name niupangzi (Template:Zh-cp; Some dictionaries list the Chinese as just 牛蒡 niúbàng.)
Burdock is a traditional medicinal herb that is used for many ailments. Burdock root oil extract, also called Bur oil, is popular in Europe as a scalp treatment applied to improve hair strength, shine and body, help reverse scalp conditions such as dandruff, and combat hair loss. Modern studies indicate that Burdock root oil extract is rich in phytosterols and essential fatty acids (including rare long-chain EFAs), the nutrients required to maintain a healthy scalp and promote natural hair growth. It combines an immediate relieving effect with nutritional support of normal functions of sebaceous glands and hair follicles.
According to some European herbalists, combining Burdock root oil with a Nettle root oil and massaging these two oils into the scalp every day has a greater effect than Bur oil alone.
# Burdock and Velcro
After taking his dog for a walk one day in the early 1940s, George de Mestral, a Swiss inventor, became curious about the seeds of the burdock plant that had attached themselves to his clothes and to the dog's fur. Under a microscope, he looked closely at the hook-and-loop system that the seeds use to hitchhike on passing animals aiding seed dispersal, and he realised that the same approach could be used to join other things together. The result was Velcro.
# Tolstoy
The Russian writer, Leo Tolstoy, wrote in his journal, 1896, about a tiny shoot of burdock he saw in a ploughed field, “black from dust but still alive and red in the center … It makes me want to write. It asserts life to the end, and alone in the midst of the whole field, somehow or other had asserted it.”
# Species
- Arctium lappa : Greater Burdock, Gobō
- Arctium minus : Lesser Burdock, Burweed, Louse-bur, Button-bur
Arctium minus nemorosum (=Arctium vulgare) : Woodland Burdock, Wood Burdock
- Arctium minus nemorosum (=Arctium vulgare) : Woodland Burdock, Wood Burdock
- Arctium pubens : Common Burdock
- Arctium tomentosum : Downy Burdock, Woolly Burdock
da:Burre (Arctium)
de:Kletten
eo:Lapo
lt:Varnalėša
nl:Klit
sr:Чичак
sv:Kardborrar
# Safety
Because the roots of burdock closely resemble those of Deadly nightshade (also known as belladonna or Atropa belladonna), there is a risk that burdock preparations may be contaminated with these potentially dangerous herbs. Be sure to buy products from established companies with good reputations. Do not gather burdock in the wild unless you know what you are doing. | Burdock
Burdock is any of a group of biennial thistles in the genus Arctium, family Asteraceae. Common Burdock (A. minus) grows wild throughout most of North America, Europe and Asia.
Plants of the genus Arctium have dark green leaves that can grow up to 18" (45 cm) long. They are generally large, coarse and ovate, with the lower ones being heart-shaped. They are woolly underneath. The leafstalks are generally hollow. Arctium species generally flower from July through October.
The prickly heads of these Old World plants are noted for easily catching on to fur and clothing, thus providing an excellent mechanism for seed dispersal. Burrs cause local irritation and can possibly cause intestinal hairballs in pets. However, most animals avoid ingesting these plants.
A large number of species have been placed in genus Arctium at one time or another, but most of them are now classified in the related genus Cousinia. The precise limits between Arctium and Cousinia are hard to define; there is an exact correlation between their molecular phylogeny. The burdocks are sometimes confused with the cockleburs (genus Xanthium) and rhubarb (genus Rheum).
The roots of burdock, among other plants, are eaten by the larva of the Ghost Moth (Hepialus humuli). The plant is used as a food plant by other Lepidoptera including Brown-tail, Coleophora paripennella, Coleophora peribenanderi, The Gothic, Lime-speck Pug and Scalloped Hazel.
The green, above-ground portions may cause contact dermatitis in humans due to the lactones the plant produces.
# Uses
## Food and drink
The taproot of young burdock plants can be harvested and eaten as a root vegetable. While generally out of favor in modern European cuisine, it remains popular in Asia, particularly in Japan where A. lappa (Greater burdock) is called gobō (牛蒡 or ゴボウ). Plants are cultivated for their slender roots, which can grow about 1 meter long and 2 cm across. Burdock root is very crisp and has a sweet, mild, and pungent flavor with a little muddy harshness that can be reduced by soaking julienne/shredded roots in water for five to ten minutes. Immature flower stalks may also be harvested in late spring, before flowers appear; the taste resembles that of artichoke, to which the burdock is related. A popular Japanese dish is kinpira gobō, julienned or shredded burdock root and carrot, braised with soy sauce, sugar, mirin and/or sake, and sesame oil; another is burdock makizushi (sushi filled with pickled burdock root rather than fish; the burdock root is often artificially colored orange to resemble a carrot). In the second half of the 20th century, burdock achieved international recognition for its culinary use due to the increasing popularity of the macrobiotic diet, which advocates its consumption. It also contains a fair amount of gobō dietary fiber (GDF, 6g per 100g), calcium, potassium, amino acids,[1] and is also low calorie. It also contains polyphenols that causes darkened surface and muddy harshness by formation of tannin-iron complexes though the harshness shows excellent harmonization with pork in miso soup (tonjiru) and Japanese-style pilaf (takikomi gohan).
Dandelion and burdock is a soft drink that has long been popular in the United Kingdom. Burdock is believed to be a galactagogue, a substance that increases lactation.
## Traditional medicine
Folk herbalists consider dried burdock to be a diuretic, diaphoretic, and a blood purifying agent. The seeds of A. lappa are used in traditional Chinese medicine, under the name niupangzi (Template:Zh-cp; Some dictionaries list the Chinese as just 牛蒡 niúbàng.)
Burdock is a traditional medicinal herb that is used for many ailments. Burdock root oil extract, also called Bur oil, is popular in Europe as a scalp treatment applied to improve hair strength, shine and body, help reverse scalp conditions such as dandruff, and combat hair loss. Modern studies indicate that Burdock root oil extract is rich in phytosterols and essential fatty acids (including rare long-chain EFAs), the nutrients required to maintain a healthy scalp and promote natural hair growth. It combines an immediate relieving effect with nutritional support of normal functions of sebaceous glands and hair follicles.
According to some European herbalists, combining Burdock root oil with a Nettle root oil and massaging these two oils into the scalp every day has a greater effect than Bur oil alone.
# Burdock and Velcro
After taking his dog for a walk one day in the early 1940s, George de Mestral, a Swiss inventor, became curious about the seeds of the burdock plant that had attached themselves to his clothes and to the dog's fur. Under a microscope, he looked closely at the hook-and-loop system that the seeds use to hitchhike on passing animals aiding seed dispersal, and he realised that the same approach could be used to join other things together. The result was Velcro.
# Tolstoy
The Russian writer, Leo Tolstoy, wrote in his journal, 1896, about a tiny shoot of burdock he saw in a ploughed field, “black from dust but still alive and red in the center … It makes me want to write. It asserts life to the end, and alone in the midst of the whole field, somehow or other had asserted it.”
# Species
- Arctium lappa : Greater Burdock, Gobō
- Arctium minus : Lesser Burdock, Burweed, Louse-bur, Button-bur
Arctium minus nemorosum (=Arctium vulgare) : Woodland Burdock, Wood Burdock
- Arctium minus nemorosum (=Arctium vulgare) : Woodland Burdock, Wood Burdock
- Arctium pubens : Common Burdock
- Arctium tomentosum : Downy Burdock, Woolly Burdock
da:Burre (Arctium)
de:Kletten
eo:Lapo
lt:Varnalėša
nl:Klit
sr:Чичак
sv:Kardborrar
# Safety
Because the roots of burdock closely resemble those of Deadly nightshade (also known as belladonna or Atropa belladonna), there is a risk that burdock preparations may be contaminated with these potentially dangerous herbs. Be sure to buy products from established companies with good reputations. Do not gather burdock in the wild unless you know what you are doing.
Template:Jb1
Template:WS | https://www.wikidoc.org/index.php/Burdock | |
eec4f046280867d3463f63fe2359a1f28a9fcdf6 | wikidoc | Burette | Burette
A burette (also buret) is a vertical cylindrical piece of laboratory glassware with a volumetric graduation on its full length and a precision tap, or stopcock, on the bottom. It is used to dispense known amounts of a liquid reagent in experiments for which such precision is necessary, such as a titration experiment. Burettes are extremely accurate: class A burettes are accurate to ±0.05 cm3.
# Using a burette
The precision of a burette makes careful measurement with a burette very important to avoid systematic error. When reading a burette, the viewer's eyes must be at the level of the graduation to avoid parallax error. Even the thickness of the lines printed on the burette matters; the bottom of the meniscus of the liquid should be touching the top of the line you wish to measure from. A common rule of thumb is to add 0.02 mL if the bottom of the meniscus is touching the bottom of the line. Due to the precision of the burette, even a single drop of liquid hanging from the bottom of a burette should be transferred to the receiving flask, usually by touching the drop to the side of the receiving flask and washing into the solution with the experimental solvent (usually water). Through careful control of the stopcock and rinsing, even partial drops of liquid can be added to the receiving flask.
# History
The history of the burette parallels the history of volumetric analysis. Francois Antoine Henri Descroizilles developed the first burette (which looked more like a graduated cylinder) in 1791. Joseph Louis Gay-Lussac developed an improved version of the burette that included a side arm, and coined the terms "pipette" and "burette" in an 1824 paper on the standarization of indigo solutions. A major breakthrough in the methodology and popularization of volumetric analysis was achieved by Karl Friedrich Mohr, who redesigned the burette by placing a clamp and a tip at the bottom. | Burette
A burette (also buret) is a vertical cylindrical piece of laboratory glassware with a volumetric graduation on its full length and a precision tap, or stopcock, on the bottom. It is used to dispense known amounts of a liquid reagent in experiments for which such precision is necessary, such as a titration experiment. Burettes are extremely accurate: class A burettes are accurate to ±0.05 cm3.
# Using a burette
The precision of a burette makes careful measurement with a burette very important to avoid systematic error. When reading a burette, the viewer's eyes must be at the level of the graduation to avoid parallax error. Even the thickness of the lines printed on the burette matters; the bottom of the meniscus of the liquid should be touching the top of the line you wish to measure from. A common rule of thumb is to add 0.02 mL if the bottom of the meniscus is touching the bottom of the line. Due to the precision of the burette, even a single drop of liquid hanging from the bottom of a burette should be transferred to the receiving flask, usually by touching the drop to the side of the receiving flask and washing into the solution with the experimental solvent (usually water). Through careful control of the stopcock and rinsing, even partial drops of liquid can be added to the receiving flask.
# History
The history of the burette parallels the history of volumetric analysis. Francois Antoine Henri Descroizilles developed the first burette (which looked more like a graduated cylinder) in 1791. Joseph Louis Gay-Lussac developed an improved version of the burette that included a side arm, and coined the terms "pipette" and "burette" in an 1824 paper on the standarization of indigo solutions. A major breakthrough in the methodology and popularization of volumetric analysis was achieved by Karl Friedrich Mohr, who redesigned the burette by placing a clamp and a tip at the bottom.[1] | https://www.wikidoc.org/index.php/Burette | |
67b48a844f3722a1ec12ea41ceb41e4bc4516ece | wikidoc | Dysuria | Dysuria
For patient information page, click here
Synonyms and keywords: Micturition painful, pain passing urine, painful urination; painful micturition
# Overview
Dysuria is define as pain or burning, stinging, or itching of the urethra or urethral meatus during or just after urination.Dysuria happens due to bladder muscle contraction and peristalsis of the urethra, which cause the urine to come in contact with the inflamed mucosal lining, which in turn stimulates pain receptors and causes one to feel pain or burning.
# Epidemiology
- Dysuria can happen in both males and females. One of the most common causes of dysuria is urinary tract infection. Urinary tract infections are more common in females than males due to female anatomy, having a shorter and straight urethra compared to males who have longer and curved urethra due to male anatomy.
- In females, bacteria can reach the bladder more easily due to shorter and straight urethra as they have less distance to travel.
- females who use the wrong wiping technique from back to front instead of front to back can predispose themselves to more frequent urinary tract infections due to the opening of the urethra being closer to the rectum. Because of these reasons, females tend to experience dysuria more frequently compared to males.
# Pathophysiology
- Dysuria from inflammatory causes like urinary tract infection results from bladder muscle contraction and urethral peristalsis, causing urine to come in contact with inflamed mucosa.
- This contact causes stimulation of sensory nerves and pain receptors and causes pain along with burning, stinging, or itching.
- The sensitivity of these receptors can become enhanced during the inflammatory or neuropathic processes
- Inflammation from the surrounding organs such as colon can also sometimes result in dysuria.
- Dysuria from non-inflammatory causes like stone, tumor, trauma, or foreign body can cause irritation of the urethral or bladder mucosa .
# Classification
Dysuria can be divided broadly into two categories
- Infectious
- Infectious causes include
- Urinary tract infection or urethritis
- Kidney or prostate infections
- Vaginal infections
- Sexually transmitted diseases
- interstitial cystitis
- Non-infectious
- Non-infectious causes include
- Foreign body or stone in the urinary tract
- Trauma
- Benign prostatic hypertrophy
- Tumors
- Certain medications
- Anatomic abnormalities
- Menopause
# Causes
## Life Threatening Causes
- Toxic epidermal necrolysis
- Stevens–Johnson syndrome
## Common Causes
- Balanitis
- Balanoposthitis
- Cervicitis
- Lower urinary tract infections
- Pelvic inflammatory disease
- Pyelonephritis
- Urethritis
- Vaginitis
## Causes by Organ System
# Causes in Alphabetical Order
- Abciximab
- Acute abacterial cystitis
- Acute cystitis
- Acute intermittent porphyria
- Acute pyelonephritis
- Acute urethritis
- Adenine phosphoribosyltransferase deficiency
- Appendicitis
- Arsenic trioxide
- Arsenicals
- Atrophic vaginitis
- Autoimmune orchitis
- Bacterial vaginosis
- Balanitis
- Balanitis xerotica obliterans
- Balanoposthitis
- Baneberry poisoning
- Behçet syndrome
- Benign prostatic hyperplasia
- Bilharziasis
- Bladder cancer
- Bladder diverticulum
- Bladder stone
- Candidal vaginitis
- Cervical cancer
- Cervicitis
- Chemical irritants
- Chlamydia
- Clofibrate
- Complication of pregnancy
- Congenital giant megaureter
- Contraceptive foam
- Contraceptive sponge
- Cystitis
- Cystocele
- Dehydration
- Diarrhea
- Dysfunctional elimination
- Ectopic pregnancy
- Endometriosis
- Eosinophilic cystitis
- Epididymitis
- Fallopian tube conditions
- Functional disorders
- Fungal infection
- Genital herpes
- Genital schistosomiasis
- Gonorrhea
- Goodpasture syndrome
- Granulomatous prostatitis
- Granulosa cell tumor of the ovary
- Hemorrhagic cystitis
- Hunner ulcer
- Hydatid cyst
- Hydroxyurea
- Hypercalciuria
- Idiopathic hyperuricosuria
- Indinavir
- Interstitial cystitis
- Irritant
- Irritative dermatitis
- Kidney infection
- Kidney stone
- Labial adhesion
- Lichen sclerosus
- Local trauma
- Lower urinary tract infection
- Malakoplakia
- Masturbation
- Meatal stenosis
- Melarsoprol
- Menopause
- Milnacipran
- Neisseria gonorrhoeae
- Non-gonococcal urethritis
- Nonspecific (chemical) urethritis
- Oxaprozin
- Paraurethral gland inflammation
- Pelvic inflammatory disease
- Pelvic lipomatosis
- Perineal trauma
- Periurethral herpes simplex
- Pinworms
- Poor perineal hygiene
- Postoperative septicaemia
- Prolapsed uterus
- Prostatic carcinoma
- Prostatic disease
- Prostatic tuberculosis
- Prostatitis
- Psychogenic disorder
- Pyelitis
- Pyelonephritis
- Pyrazinamide
- Radiation therapy
- Reactive arthritis
- Rectovesical fistula
- Reiter's Syndrome
- Renal nutcracker syndrome
- Renal tuberculosis
- Schistosoma haematobium
- Sexual abuse
- Sexually transmitted disease
- Spermicidal gel
- Stevens-Johnson syndrome
- Tiagabine
- Tiaprofenic acid
- Toxic epidermal necrolysis
- Trauma
- Trichomoniasis
- Urethral cancer
- Urethral caruncle
- Urethral catheterization
- Urethral stricture
- Urethral syndrome
- Urethral trauma
- Urethritis
- Urinary incontinence
- Urinary obstruction
- Urinary stone
- Urinary tract infection
- Urinary tract malformation
- Urinary tract neoplasm
- Urolithiasis
- Vaginal douche
- Vaginal lubricant
- Vaginal ulcers
- Vaginitis
- Valrubicin
- Vancomycin resistant enterococcal bacteremia
- Varicella
- Vesical calculus
- Vesicoureteral reflux
- Vesicovaginal fistula
- Vulvar cancer
- Vulvitis
- Xanthine oxydase deficiency
- Xanthinuria
- X-linked alpha thalassemia mental retardation syndrome
# Treatment
Treatment of dysuria depends on its cause the most common cause of dysuria is urinary tract infection for which empiric antibiotic are used.If the cause of dysuria is renal stones, then various treatment options can be considered depending on the size and location of stones. Stones smaller than 5 mm typically pass on their own, and patients should be asked to hydrate themselves and strain the urine to document the evidence of a passed stone. The stones that are bigger than 5 mm are treatable through various modalities, including extracorporeal shock wave lithotripsy (ESWL) or percutaneous nephrolithotomy (PCNL) or open surgery.
When dysuria is occurring due to chronic prostatitis in males, oral antibiotics merit consideration after obtaining urine culture. | Dysuria
For patient information page, click here
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Kiran Singh, M.D. [2] Associate Editor(s)-in-Chief: nabeel ahmed
Synonyms and keywords: Micturition painful, pain passing urine, painful urination; painful micturition
# Overview
Dysuria is define as pain or burning, stinging, or itching of the urethra or urethral meatus during or just after urination.Dysuria happens due to bladder muscle contraction and peristalsis of the urethra, which cause the urine to come in contact with the inflamed mucosal lining, which in turn stimulates pain receptors and causes one to feel pain or burning.
# Epidemiology
- Dysuria can happen in both males and females. One of the most common causes of dysuria is urinary tract infection. Urinary tract infections are more common in females than males due to female anatomy, having a shorter and straight urethra compared to males who have longer and curved urethra due to male anatomy.
- In females, bacteria can reach the bladder more easily due to shorter and straight urethra as they have less distance to travel.
- females who use the wrong wiping technique from back to front instead of front to back can predispose themselves to more frequent urinary tract infections due to the opening of the urethra being closer to the rectum. Because of these reasons, females tend to experience dysuria more frequently compared to males.
# Pathophysiology
- Dysuria from inflammatory causes like urinary tract infection results from bladder muscle contraction and urethral peristalsis, causing urine to come in contact with inflamed mucosa.
- This contact causes stimulation of sensory nerves and pain receptors and causes pain along with burning, stinging, or itching.
- The sensitivity of these receptors can become enhanced during the inflammatory or neuropathic processes
- Inflammation from the surrounding organs such as colon can also sometimes result in dysuria.[1]
- Dysuria from non-inflammatory causes like stone, tumor, trauma, or foreign body can cause irritation of the urethral or bladder mucosa .[2]
# Classification
Dysuria can be divided broadly into two categories
- Infectious
- Infectious causes include
- Urinary tract infection or urethritis
- Kidney or prostate infections
- Vaginal infections
- Sexually transmitted diseases
- interstitial cystitis
- Non-infectious
- Non-infectious causes include
- Foreign body or stone in the urinary tract
- Trauma
- Benign prostatic hypertrophy
- Tumors
- Certain medications
- Anatomic abnormalities
- Menopause [3]
# Causes
## Life Threatening Causes
- Toxic epidermal necrolysis
- Stevens–Johnson syndrome
## Common Causes
- Balanitis
- Balanoposthitis
- Cervicitis
- Lower urinary tract infections
- Pelvic inflammatory disease
- Pyelonephritis
- Urethritis
- Vaginitis
## Causes by Organ System
# Causes in Alphabetical Order
- Abciximab
- Acute abacterial cystitis
- Acute cystitis
- Acute intermittent porphyria
- Acute pyelonephritis
- Acute urethritis
- Adenine phosphoribosyltransferase deficiency
- Appendicitis
- Arsenic trioxide
- Arsenicals
- Atrophic vaginitis
- Autoimmune orchitis
- Bacterial vaginosis
- Balanitis
- Balanitis xerotica obliterans
- Balanoposthitis
- Baneberry poisoning
- Behçet syndrome
- Benign prostatic hyperplasia
- Bilharziasis
- Bladder cancer
- Bladder diverticulum
- Bladder stone
- Candidal vaginitis
- Cervical cancer
- Cervicitis
- Chemical irritants
- Chlamydia
- Clofibrate
- Complication of pregnancy
- Congenital giant megaureter
- Contraceptive foam
- Contraceptive sponge
- Cystitis
- Cystocele
- Dehydration
- Diarrhea
- Dysfunctional elimination
- Ectopic pregnancy
- Endometriosis
- Eosinophilic cystitis
- Epididymitis
- Fallopian tube conditions
- Functional disorders
- Fungal infection
- Genital herpes
- Genital schistosomiasis
- Gonorrhea
- Goodpasture syndrome
- Granulomatous prostatitis
- Granulosa cell tumor of the ovary
- Hemorrhagic cystitis
- Hunner ulcer
- Hydatid cyst
- Hydroxyurea
- Hypercalciuria
- Idiopathic hyperuricosuria
- Indinavir
- Interstitial cystitis
- Irritant
- Irritative dermatitis
- Kidney infection
- Kidney stone
- Labial adhesion
- Lichen sclerosus
- Local trauma
- Lower urinary tract infection
- Malakoplakia
- Masturbation
- Meatal stenosis
- Melarsoprol
- Menopause
- Milnacipran
- Neisseria gonorrhoeae
- Non-gonococcal urethritis
- Nonspecific (chemical) urethritis
- Oxaprozin
- Paraurethral gland inflammation
- Pelvic inflammatory disease
- Pelvic lipomatosis
- Perineal trauma
- Periurethral herpes simplex
- Pinworms
- Poor perineal hygiene
- Postoperative septicaemia
- Prolapsed uterus
- Prostatic carcinoma
- Prostatic disease
- Prostatic tuberculosis
- Prostatitis
- Psychogenic disorder
- Pyelitis
- Pyelonephritis
- Pyrazinamide
- Radiation therapy
- Reactive arthritis
- Rectovesical fistula
- Reiter's Syndrome
- Renal nutcracker syndrome
- Renal tuberculosis
- Schistosoma haematobium
- Sexual abuse
- Sexually transmitted disease
- Spermicidal gel
- Stevens-Johnson syndrome
- Tiagabine
- Tiaprofenic acid
- Toxic epidermal necrolysis
- Trauma
- Trichomoniasis
- Urethral cancer
- Urethral caruncle
- Urethral catheterization
- Urethral stricture
- Urethral syndrome
- Urethral trauma
- Urethritis
- Urinary incontinence
- Urinary obstruction
- Urinary stone
- Urinary tract infection
- Urinary tract malformation
- Urinary tract neoplasm
- Urolithiasis
- Vaginal douche
- Vaginal lubricant
- Vaginal ulcers
- Vaginitis
- Valrubicin
- Vancomycin resistant enterococcal bacteremia
- Varicella
- Vesical calculus
- Vesicoureteral reflux
- Vesicovaginal fistula
- Vulvar cancer
- Vulvitis
- Xanthine oxydase deficiency
- Xanthinuria
- X-linked alpha thalassemia mental retardation syndrome
# Treatment
Treatment of dysuria depends on its cause the most common cause of dysuria is urinary tract infection for which empiric antibiotic are used.[4]If the cause of dysuria is renal stones, then various treatment options can be considered depending on the size and location of stones. Stones smaller than 5 mm typically pass on their own, and patients should be asked to hydrate themselves and strain the urine to document the evidence of a passed stone. The stones that are bigger than 5 mm are treatable through various modalities, including extracorporeal shock wave lithotripsy (ESWL) or percutaneous nephrolithotomy (PCNL) or open surgery.
When dysuria is occurring due to chronic prostatitis in males, oral antibiotics merit consideration after obtaining urine culture.[5] | https://www.wikidoc.org/index.php/Burning_during_urination | |
d27afd63cf3ebef596b846e67c0634e8595074f6 | wikidoc | C11orf1 | C11orf1
Chromosome 11 open reading frame one, also known as C11orf1, is a protein-coding gene. It has been found by yeast two hybrid screen to bind to SETDB1 a histone protein methyltranferase enzyme. SETDB1 has been implicated in Huntington's disease, a neurodegenerative disorder.
C11orf1 is a nuclear protein with unknown function but has been shown to show preferential expression in some disease states in microarray data.
# Species distribution
C11orf1 shows conservation through mammals and orthologs can be found in sea squirts and sea anemone. The below table shows some orthologs found using BLAST.
# Gene
C11orf1 is located on chromosome 11 and is neighbored by:
- FDXACB1-201
- ALG9-201
- ALG9-202
- AP001781.5-201
# Protein
## Structure
This protein is part of the UPF0686 superfamily. This family is characterized by the presence of a domain of unknown function (DUF)1143 shared by the family. This family DUF1143 has a domain that includes almost all,149, of the 150 amino acids in the human ortholog. C11orf1 has six spicesomal variants and one unspliced variant.
## Predicted properties
The following properties of C11orf1 were predicted using bioinformatic analysis:
- Molecular Weight: 17.76 KDal
- Isoelectric point: 7.28
- Post-translational modification: twelve possible post-translational modifications are predicted:
Two O-(N-acetylaminogalactosyl)-L-threonine Glycosylations at position 138 and 142 on the protein sequence
Two O-phospho-L-serine Phosphorylation sites at 112 and 141.
Four O-phospho-L-threonine Phosphorylation sites at 59, 99, 113, and 138.
Four O4'-phospho-L-tyrosine Phosphorylation sites at 64, 101, 105 and 143.
- Two O-(N-acetylaminogalactosyl)-L-threonine Glycosylations at position 138 and 142 on the protein sequence
- Two O-phospho-L-serine Phosphorylation sites at 112 and 141.
- Four O-phospho-L-threonine Phosphorylation sites at 59, 99, 113, and 138.
- Four O4'-phospho-L-tyrosine Phosphorylation sites at 64, 101, 105 and 143.
## Tissue distribution
C11orf1 appears to be ubiquitously expressed at low levels but particularly high expression in the parathyroid. Expression data indicate expression in most tissues. This gene has also been found in one experiment to be under expressed in Huntington's disease patients while SETDB1 is over-expressed.
## Binding partners
The human protein SET domain bifurcated 1, was found to be a binding partner for C11orf1 by Yeast Two Hybrid. | C11orf1
Chromosome 11 open reading frame one, also known as C11orf1, is a protein-coding gene.[1] It has been found by yeast two hybrid screen to bind to SETDB1 a histone protein methyltranferase enzyme. SETDB1 has been implicated in Huntington's disease, a neurodegenerative disorder.[2]
C11orf1 is a nuclear protein with unknown function but has been shown to show preferential expression in some disease states in microarray data.[3][4]
# Species distribution
C11orf1 shows conservation through mammals and orthologs can be found in sea squirts and sea anemone. The below table shows some orthologs found using BLAST.[5]
# Gene
C11orf1 is located on chromosome 11 and is neighbored by:
- FDXACB1-201
- ALG9-201
- ALG9-202
- AP001781.5-201
# Protein
## Structure
This protein is part of the UPF0686 superfamily. This family is characterized by the presence of a domain of unknown function (DUF)1143 shared by the family.[6] This family DUF1143 has a domain that includes almost all,149, of the 150 amino acids in the human ortholog. C11orf1 has six spicesomal variants and one unspliced variant.
## Predicted properties
The following properties of C11orf1 were predicted using bioinformatic analysis:
- Molecular Weight: 17.76 KDal[7]
- Isoelectric point: 7.28[8]
- Post-translational modification: twelve possible post-translational modifications are predicted:
Two O-(N-acetylaminogalactosyl)-L-threonine Glycosylations at position 138 and 142 on the protein sequence[9]
Two O-phospho-L-serine Phosphorylation sites at 112 and 141.[9]
Four O-phospho-L-threonine Phosphorylation sites at 59, 99, 113, and 138.[9]
Four O4'-phospho-L-tyrosine Phosphorylation sites at 64, 101, 105 and 143.[9]
- Two O-(N-acetylaminogalactosyl)-L-threonine Glycosylations at position 138 and 142 on the protein sequence[9]
- Two O-phospho-L-serine Phosphorylation sites at 112 and 141.[9]
- Four O-phospho-L-threonine Phosphorylation sites at 59, 99, 113, and 138.[9]
- Four O4'-phospho-L-tyrosine Phosphorylation sites at 64, 101, 105 and 143.[9]
## Tissue distribution
C11orf1 appears to be ubiquitously expressed at low levels but particularly high expression in the parathyroid. Expression data indicate expression in most tissues.[10] This gene has also been found in one experiment to be under expressed in Huntington's disease patients while SETDB1 is over-expressed.[3]
## Binding partners
The human protein SET domain bifurcated 1, was found to be a binding partner for C11orf1 by Yeast Two Hybrid.[11] | https://www.wikidoc.org/index.php/C11orf1 | |
0631f030b7bf49de414fe1974d7db72a306fa5c2 | wikidoc | C19orf2 | C19orf2
Unconventional prefoldin RPB5 interactor, also called URI1, is a protein that in humans is encoded by the C19orf2 gene.
# Function
The protein encoded by this gene binds to RNA polymerase II subunit 5 (RPB5) and negatively modulates transcription through its binding to RPB5. The encoded protein seems to have inhibitory effects on various types of activated transcription, but it requires the RPB5-binding region. This protein acts as a corepressor. It is suggested that it may require signaling processes for its function or that it negatively modulates genes in the chromatin structure. Two alternatively spliced transcript variants encoding different isoforms have been described for this gene.
# Interactions
C19orf2 has been shown to interact with DMAP1 and STAP1.
# Model organisms
Model organisms have been used in the study of URI1 function. A conditional knockout mouse line called Uri1tm1a(EUCOMM)Wtsi was generated at the Wellcome Trust Sanger Institute. Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion. Additional screens performed: - In-depth immunological phenotyping | C19orf2
Unconventional prefoldin RPB5 interactor, also called URI1, is a protein that in humans is encoded by the C19orf2 gene.[1][2][3]
# Function
The protein encoded by this gene binds to RNA polymerase II subunit 5 (RPB5) and negatively modulates transcription through its binding to RPB5. The encoded protein seems to have inhibitory effects on various types of activated transcription, but it requires the RPB5-binding region. This protein acts as a corepressor. It is suggested that it may require signaling processes for its function or that it negatively modulates genes in the chromatin structure. Two alternatively spliced transcript variants encoding different isoforms have been described for this gene.[3]
# Interactions
C19orf2 has been shown to interact with DMAP1[4] and STAP1.[5]
# Model organisms
Model organisms have been used in the study of URI1 function. A conditional knockout mouse line called Uri1tm1a(EUCOMM)Wtsi was generated at the Wellcome Trust Sanger Institute.[6] Male and female animals underwent a standardized phenotypic screen[7] to determine the effects of deletion.[8][9][10][11] Additional screens performed: - In-depth immunological phenotyping[12] | https://www.wikidoc.org/index.php/C19orf2 | |
0c96c6f94fa912276a7ab5d086ded1f5612be706 | wikidoc | C1GALT1 | C1GALT1
Core 1 synthase, glycoprotein-N-acetylgalactosamine 3-beta-galactosyltransferase, 1, also known as C1GALT1, is an enzyme which in humans is encoded by the C1GALT1 gene.
# Function
The common core 1 O-glycan structure Gal-beta-1-3GalNAc-R is a precursor for many extended mucin-type O-glycan structures in animal cell surface and secreted glycoproteins. Core 1 is synthesized by the transfer of Gal from UDP-Gal to GalNAc-alpha-1-R by core 1 beta-3-galactosyltransferase (C1GALT1).
C1GALT1 is associated with the T-Tn antigen system.
# Clinical significance
There is some evidence that mutations in the C1GALT1 gene may be associated with kidney disease. | C1GALT1
Core 1 synthase, glycoprotein-N-acetylgalactosamine 3-beta-galactosyltransferase, 1, also known as C1GALT1, is an enzyme which in humans is encoded by the C1GALT1 gene.[1][2]
# Function
The common core 1 O-glycan structure Gal-beta-1-3GalNAc-R is a precursor for many extended mucin-type O-glycan structures in animal cell surface and secreted glycoproteins. Core 1 is synthesized by the transfer of Gal from UDP-Gal to GalNAc-alpha-1-R by core 1 beta-3-galactosyltransferase (C1GALT1).[2]
C1GALT1 is associated with the T-Tn antigen system.[3]
# Clinical significance
There is some evidence that mutations in the C1GALT1 gene may be associated with kidney disease.[4] | https://www.wikidoc.org/index.php/C1GALT1 | |
8702def46f1a1a04cd3f82f4e234c36b560cf97e | wikidoc | C1QTNF5 | C1QTNF5
C1q and tumor necrosis factor related protein 5, also known as C1QTNF5, is a protein which in humans is encoded by the C1QTNF5 gene . The C1QTNF5 gene secreted and membrane-linked to a protein which is strongly expressed in retinal pigment epithelium cells(RPE).
# Function
The CTRP5 protein is a member of the C1q / tumor necrosis factor superfamily, which shows diverse functions including cell adhesion and as components of the basement membrane.
# Clinical significance
A mutation in the C1QTNF5 gene causes late-onset retinal degeneration.
More specifically, a single missense mutation (S163R) in the encoded C1QTNF5 protein causes the Late-onset retinal degeneration disease(L-ORD).
# Structure
The structure of C1q and Tumor Necrosis Factor Related Protein 5 (C1QTNF5) which is also called CTRP5 has three essential domains. The first domain is a single peptide which is located in N-terminal, the second domain is a collage domain and the third domain is a globular complementment 1q (gC1q) that exists in the C-terminal domain. The single mutation S163R is found in the gC1q domain which is the main reason for Late-onset retinal degeneration disease(L-ORD).C1QTNF5 is a part of the C1q family. However, there is a unique feature of the structure of C1QTNF5 that it does not own a Ca 2+ binding site as other members of the C1q family.
# Crystal structure
Crystal structure of C1QTNF5 has been taken by Xiongying and Krzysztof and it has two characteristics. One is that the structure of C1QTNF5 seems not to have a Ca 2+ binding site in order to its stability. Also, it is necessary for the function of the members of the C1q family. Another feature is having an unusual sequence which is (F181, F182, G183, G184, W185, P186) that generate a hydrophobic field. In this area, S163 and F182 build H bond, However, the mutation S163 will make a disruption to the H bond. | C1QTNF5
C1q and tumor necrosis factor related protein 5, also known as C1QTNF5, is a protein which in humans is encoded by the C1QTNF5 gene . [1][2]The C1QTNF5 gene secreted and membrane-linked to a protein which is strongly expressed in retinal pigment epithelium cells(RPE).[3][4][5]
# Function
The CTRP5 protein is a member of the C1q / tumor necrosis factor superfamily, which shows diverse functions including cell adhesion and as components of the basement membrane.[6]
# Clinical significance
A mutation in the C1QTNF5 gene causes late-onset retinal degeneration.[2]
More specifically, a single missense mutation (S163R) in the encoded C1QTNF5 protein causes the Late-onset retinal degeneration disease(L-ORD).[1]
# Structure
The structure of C1q and Tumor Necrosis Factor Related Protein 5 (C1QTNF5) which is also called CTRP5[7] has three essential domains. The first domain is a single peptide which is located in N-terminal, the second domain is a collage domain and the third domain is a globular complementment 1q (gC1q) that exists in the C-terminal domain.[4][8][9][3] [10]The single mutation S163R is found in the gC1q domain which is the main reason for Late-onset retinal degeneration disease(L-ORD).[3][5][4][10]C1QTNF5 is a part of the C1q family. However, there is a unique feature of the structure of C1QTNF5 that it does not own a Ca 2+ binding site as other members of the C1q family.[3]
# Crystal structure
Crystal structure of C1QTNF5 has been taken by Xiongying and Krzysztof and it has two characteristics. One is that the structure of C1QTNF5 seems not to have a Ca 2+ binding site in order to its stability. Also, it is necessary for the function of the members of the C1q family. Another feature is having an unusual sequence which is (F181, F182, G183, G184, W185, P186) that generate a hydrophobic field. In this area, S163 and F182 build H bond, However, the mutation S163 will make a disruption to the H bond.[3] | https://www.wikidoc.org/index.php/C1QTNF5 | |
52e4bbb4522377b87391b5be610d256b56730fd2 | wikidoc | C1orf27 | C1orf27
Uncharacterized protein Chromosome 1 Open Reading Frame 27 is a protein in humans, encoded by the C1orf27 gene. It is accession number NM_017847. This is a membrane protein that is 3926 base pairs long with the most extensive string of amino acids being 454aa long. C1orf27 exhibits cytoplasmic expression in epidermal tissues. Predicted associated biological processes of the gene include cell fate specification and developmental properties.
# Gene
## Locus
This gene is located on chromosome 1 at 1q31.1. It is encoded on the plus strand of DNA spanning from 186,344,406 to 186,390,514.
# mRNA
## Alternative splicing
There appear to be four isoforms due to splicing. Two of those are truncated on the 3' end of the protein from 266aa and 396aa. Additional location of alternative splice sites are from 79aa to 102aa and 246aa to 260aa.
# Protein
## General properties
The primary encoded protein of C1orf27 consists of 454 amino acid residues and is 3926 base pairs long. It consists of 14 total exons. The predicted molecular weight of the primary, unmodified protein is approximately 51.1 kdal.
## Aliases
As with many other genes, there are some common aliases found with this gene. Those aliases are Lymphocyte-Activation Gene-1 (LAG1) Interacting Protein, Transparent Testa Glabra 1 (TTG1), and Odorant Response Abnormal 4 (ODR4). The most common alias for C1orf27 is ODR4, and this is what most readily appears when searching the gene.
## Composition
Computational analysis revealed the most abundant amino acid to be leucine at 10.1% of the total protein. The second most abundant was serine which contributes to 8.6% of the total protein. Glutamic acid was third most abundant and contributes to 7.7% of the protein. This analysis also revealed that the protein appears to be deficient in tryptophan as it only contributes to 1.1% of the protein. Based on the distribution of other amino acid types, there were five high scoring hydrophobic segments. There were also two transmembrane domains located at 82-98aa and 432-449aa.
## Post-translational modifications
C1orf27 is predicted to undergo multiple post translational modifications such as glycosylation, myristoylation, and phosphorylation.
## Interactions
There were eight interactions identified by Mentha. The first one was UFSP2 which hydrolyzes the peptide bond at the C-term gly of UFM1, a ubiquitin-like modifier protein bound to a number of target proteins. The second one was HSCB which acts as a co-chaperone in iron-sulfur cluster assembly in mitochondria. The third was GRB2 which is an adapter protein that provides a critical link between cell surface growth factor receptors and the Ras signaling pathway. The fourth was CYLD which is a protease that cleaves Lys-63-linked polyubiquitin chains, controls regulation of cell survival, proliferation, and differentiation, and is required for normal cell cycle progress. The fifth was ATM which activates checkpoint signaling upon double strand breaks, apaptosis, and genotoxic stress. The sixth was FAM177A1, the function of which is unknown. The last two were THID2 and Q81kP6 which are both in bacillus anthracis.
## Subcellular localization
The c1orf27 protein is likely cytoplasmic. This was found with 55.5 reliability. The K-NN prediction was k=9/23 and the protein was found to be 55.6% cytoplasmic, 11.1% mitochondrial, 11.1% vacuolar, 11.1% cytoskeletal, and 11.1% golgi.
## Structure
Alpha helices predicted in the c1orf27 protein are colored blue in the above picture. Beta sheets are pictured by the red arrows. Random coils are the purple strands between structures.
## Expression
Overall, expression of c1orf27 seems to be ubiquitous. Highest expression body sites (>50 TPM) were bladder, bone marrow, kidney, liver, pancreas, parathyroid, and vascular. Highest expression health sites (>50 TPM) were adrenal tumors, cervical tumors, and liver tumors. While both of these observations had relatively high TPM scores, there was still relatively low occurrence. This validates the assumption that expression is ubiquitous. There was moderate expression (>25 TPM) in the human fetus, and expression increased with age. Expression was completely absent in the ears, esophagus, lymph, nerve, salivary glands, thyroid, tonsils, and umbilical cord. There was no expression in bladder carcinoma despite expression being elevated in the bladder itself. There was high expression in endothelial cells and neuronal cells but was undetectable in glial cells and neuropil cells. Expression was also localized to the nucleoplasm and plasma membrane in humans but is localized to the cytosol in mice.
# Homology
## Paralogs
There were no paralogs of C1orf27 identified in the human genome.
## Orthologs
There were orthologs identified in most animals for which there were complete genome data. The most distant, yet still relevant, orthologs identified were invertebrates from phylum Cnidaria.
## Molecular Evolution
The m value, or number of corrected amino acid changes per 100 residues, for the C1orf27 gene was graphed against the species divergence in millions of years. When compared to divergence graphs of fibrinogen and cytochrome C, it was determined that this gene closely resembles the evolutionary pattern observed in fibrinogen, suggesting a more rapid rate of evolution. M values for C1orf27 were calculated using the percentage of identity, when compared to humans, observed in the mRNA sequences of the orthologs using the formula derived from the Molecular Clock Hypothesis. | C1orf27
Uncharacterized protein Chromosome 1 Open Reading Frame 27 is a protein in humans, encoded by the C1orf27 gene. It is accession number NM_017847[1]. This is a membrane protein that is 3926 base pairs long with the most extensive string of amino acids being 454aa long. C1orf27 exhibits cytoplasmic expression in epidermal tissues.[2] Predicted associated biological processes of the gene include cell fate specification and developmental properties.[3]
# Gene
## Locus
This gene is located on chromosome 1 at 1q31.1.[4] It is encoded on the plus strand of DNA spanning from 186,344,406 to 186,390,514.
# mRNA
## Alternative splicing
There appear to be four isoforms due to splicing[5]. Two of those are truncated on the 3' end of the protein from 266aa and 396aa. Additional location of alternative splice sites are from 79aa to 102aa and 246aa to 260aa.
# Protein
## General properties
The primary encoded protein of C1orf27 consists of 454 amino acid residues and is 3926 base pairs long.[1] It consists of 14 total exons. The predicted molecular weight of the primary, unmodified protein is approximately 51.1 kdal.
## Aliases
As with many other genes, there are some common aliases found with this gene.[6] Those aliases are Lymphocyte-Activation Gene-1 (LAG1) Interacting Protein, Transparent Testa Glabra 1 (TTG1), and Odorant Response Abnormal 4 (ODR4). The most common alias for C1orf27 is ODR4, and this is what most readily appears when searching the gene.
## Composition
Computational analysis revealed the most abundant amino acid to be leucine at 10.1% of the total protein[7]. The second most abundant was serine which contributes to 8.6% of the total protein. Glutamic acid was third most abundant and contributes to 7.7% of the protein. This analysis also revealed that the protein appears to be deficient in tryptophan as it only contributes to 1.1% of the protein[7]. Based on the distribution of other amino acid types, there were five high scoring hydrophobic segments. There were also two transmembrane domains located at 82-98aa and 432-449aa.
## Post-translational modifications
C1orf27 is predicted to undergo multiple post translational modifications such as glycosylation, myristoylation, and phosphorylation[14].
## Interactions
There were eight interactions identified by Mentha[15]. The first one was UFSP2 which hydrolyzes the peptide bond at the C-term gly of UFM1, a ubiquitin-like modifier protein bound to a number of target proteins. The second one was HSCB which acts as a co-chaperone in iron-sulfur cluster assembly in mitochondria. The third was GRB2 which is an adapter protein that provides a critical link between cell surface growth factor receptors and the Ras signaling pathway. The fourth was CYLD which is a protease that cleaves Lys-63-linked polyubiquitin chains, controls regulation of cell survival, proliferation, and differentiation, and is required for normal cell cycle progress. The fifth was ATM which activates checkpoint signaling upon double strand breaks, apaptosis, and genotoxic stress. The sixth was FAM177A1, the function of which is unknown. The last two were THID2 and Q81kP6 which are both in bacillus anthracis.
## Subcellular localization
The c1orf27 protein is likely cytoplasmic[16]. This was found with 55.5 reliability. The K-NN prediction was k=9/23 and the protein was found to be 55.6% cytoplasmic, 11.1% mitochondrial, 11.1% vacuolar, 11.1% cytoskeletal, and 11.1% golgi.
## Structure
Alpha helices predicted in the c1orf27 protein are colored blue in the above picture. Beta sheets are pictured by the red arrows. Random coils are the purple strands between structures.
## Expression
Overall, expression of c1orf27 seems to be ubiquitous[19]. Highest expression body sites (>50 TPM) were bladder, bone marrow, kidney, liver, pancreas, parathyroid, and vascular. Highest expression health sites (>50 TPM) were adrenal tumors, cervical tumors, and liver tumors. While both of these observations had relatively high TPM scores, there was still relatively low occurrence. This validates the assumption that expression is ubiquitous. There was moderate expression (>25 TPM) in the human fetus, and expression increased with age[19]. Expression was completely absent in the ears, esophagus, lymph, nerve, salivary glands, thyroid, tonsils, and umbilical cord. There was no expression in bladder carcinoma despite expression being elevated in the bladder itself. There was high expression in endothelial cells and neuronal cells but was undetectable in glial cells and neuropil cells. Expression was also localized to the nucleoplasm and plasma membrane in humans but is localized to the cytosol in mice.
# Homology
## Paralogs
There were no paralogs of C1orf27 identified in the human genome.[5]
## Orthologs
There were orthologs identified in most animals for which there were complete genome data.[5] The most distant, yet still relevant, orthologs identified were invertebrates from phylum Cnidaria.
## Molecular Evolution
The m value, or number of corrected amino acid changes per 100 residues, for the C1orf27 gene was graphed against the species divergence in millions of years. When compared to divergence graphs of fibrinogen and cytochrome C, it was determined that this gene closely resembles the evolutionary pattern observed in fibrinogen, suggesting a more rapid rate of evolution. M values for C1orf27 were calculated using the percentage of identity, when compared to humans, observed in the mRNA sequences of the orthologs using the formula derived from the Molecular Clock Hypothesis. | https://www.wikidoc.org/index.php/C1orf27 | |
e5226a49e7e785c0eb902033d8b6ecce31c97117 | wikidoc | C1orf74 | C1orf74
UPF0739 protein C1orf74 is a protein that in humans is encoded by the C1orf74 gene.
# Gene
The gene C1orf74 is a protein-encoding gene on chromosome 1 in humans. It is also known as URLC4 in humans. The locus of this gene is 1q32.2. C1orf74 is 2229 base pairs long. The gene contains two exons.
C1orf74 is downstream of the gene interferon regulatory factor 6 or IRF6 in humans.
# Transcript
C1orf74 is transcribed into an mRNA that is 1642 nucleotides long in humans. The transcript contains two exons and one upstream in-frame stop codon. The 5' UTR of this transcript is 343 nucleotides long and the 3' UTR is 570 nucleotides long.
Both exons are usually transcribed. A few cases exist where only the second exon was transcribed. A fusion transcript containing IRF6 and the first exon of C1orf74 has also been found, but this transcript results in a short polypeptide.
# Protein
The protein that is encoded by C1orf74 in humans is most commonly known as UPF0739 protein C1orf74. The human version of UPF0739 contains 269 amino acids and weighs 29430 Da. Amino acids 19 to 269 are part of a domain of unknown function known as DUF4504. Within this DUF, there are two conserved sequence motifs LLGYP and SFS.
The translational start site of C1orf74 is after the exon-exon junction, which means the protein is made only by translating the second exon.
# Expression
C1orf74 is ubiquitously expressed in most tissues in humans during embryonic development and through adulthood. This gene is expressed throughout the nervous system, mammary and salivary glands, skin, and most internal organs.
# Function
One suggestion of C1orf74's function in humans comes from data that has been published only in NCBI from a paper that will come out later this year by Daigo and Nakamura. The authors found that C1orf74 is up-regulated in lung cancer and they have added the alias URLC4 to this protein (BAQ19750).
C1orf74's locus, 1q32.2, has been associated with schizophrenia. This means that C1orf74, or its neighbors, contribute to the risk of schizophrenia. A mutation in IRF6, C1orf74's upstream neighbor, results in cleft palate and Van der Woude syndrome. Mutations in regions upstream and downstream of IRF6, such as C1orf74, may also result in Van der Woude syndrome or these mutations may work with a mutation in IRF6 to result in the disease.
# Evolution
The human gene C1orf74 does not have any known paralogs, but it has many orthologs that contain the same DUF. It has orthologs in most vertebrates and some invertebrates, like worms, leeches and sea snails. Some of C1orf74's orthologs include mouse, hedgehog, chicken, zebrafish, alligator, and leech. C1orf74 has a distant ortholog in white rust (Albugo candida), which is a type of oomycete and not a true fungus. No orthologs were found in plants, fungi, or bacteria. | C1orf74
UPF0739 protein C1orf74 is a protein that in humans is encoded by the C1orf74 gene.[1]
# Gene
The gene C1orf74 is a protein-encoding gene on chromosome 1 in humans.[1][2] It is also known as URLC4 in humans. The locus of this gene is 1q32.2. C1orf74 is 2229 base pairs long. The gene contains two exons.
C1orf74 is downstream of the gene interferon regulatory factor 6 or IRF6 in humans.[3]
# Transcript
C1orf74 is transcribed into an mRNA that is 1642 nucleotides long in humans.[4] The transcript contains two exons and one upstream in-frame stop codon. The 5' UTR of this transcript is 343 nucleotides long and the 3' UTR is 570 nucleotides long.
Both exons are usually transcribed.[5] A few cases exist where only the second exon was transcribed. A fusion transcript containing IRF6 and the first exon of C1orf74 has also been found, but this transcript results in a short polypeptide.[6]
# Protein
The protein that is encoded by C1orf74 in humans is most commonly known as UPF0739 protein C1orf74.[7] The human version of UPF0739 contains 269 amino acids and weighs 29430 Da. Amino acids 19 to 269 are part of a domain of unknown function known as DUF4504. Within this DUF, there are two conserved sequence motifs LLGYP and SFS.
The translational start site of C1orf74 is after the exon-exon junction, which means the protein is made only by translating the second exon.
# Expression
C1orf74 is ubiquitously expressed in most tissues in humans during embryonic development and through adulthood.[8] This gene is expressed throughout the nervous system, mammary and salivary glands, skin, and most internal organs.
# Function
One suggestion of C1orf74's function in humans comes from data that has been published only in NCBI from a paper that will come out later this year by Daigo and Nakamura. The authors found that C1orf74 is up-regulated in lung cancer and they have added the alias URLC4 to this protein (BAQ19750).
C1orf74's locus, 1q32.2, has been associated with schizophrenia.[9] This means that C1orf74, or its neighbors, contribute to the risk of schizophrenia. A mutation in IRF6, C1orf74's upstream neighbor, results in cleft palate and Van der Woude syndrome.[10] Mutations in regions upstream and downstream of IRF6, such as C1orf74, may also result in Van der Woude syndrome or these mutations may work with a mutation in IRF6 to result in the disease.
# Evolution
The human gene C1orf74 does not have any known paralogs, but it has many orthologs that contain the same DUF. It has orthologs in most vertebrates and some invertebrates, like worms, leeches and sea snails.[11] Some of C1orf74's orthologs include mouse, hedgehog, chicken, zebrafish, alligator, and leech. C1orf74 has a distant ortholog in white rust (Albugo candida), which is a type of oomycete and not a true fungus.[12] No orthologs were found in plants, fungi, or bacteria. | https://www.wikidoc.org/index.php/C1orf74 | |
2abcb6794572a562875e0a9aee6a0632f3f0e267 | wikidoc | C2orf18 | C2orf18
Transmembrane protein C2orf18 is a protein that in humans is encoded by the C2orf18 gene. The orthologue in mice is 4930471M23Rik.
# Model organisms
Model organisms have been used in the study of C2orf18 function. A conditional knockout mouse line, called 4930471M23Riktm1a(EUCOMM)Wtsi was generated as part of the International Knockout Mouse Consortium program — a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists — at the Wellcome Trust Sanger Institute.
Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion. Twenty two tests were carried out on mutant mice, but no significant abnormalities were observed. | C2orf18
Transmembrane protein C2orf18 is a protein that in humans is encoded by the C2orf18 gene.[1][2] The orthologue in mice is 4930471M23Rik.[2]
# Model organisms
Model organisms have been used in the study of C2orf18 function. A conditional knockout mouse line, called 4930471M23Riktm1a(EUCOMM)Wtsi[7][8] was generated as part of the International Knockout Mouse Consortium program — a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists — at the Wellcome Trust Sanger Institute.[9][10][11]
Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion.[5][12] Twenty two tests were carried out on mutant mice, but no significant abnormalities were observed.[5] | https://www.wikidoc.org/index.php/C2orf18 | |
f9ff3f11099db27dc07ba1c35a6c8f8ecb031f20 | wikidoc | C2orf73 | C2orf73
Uncharacterized protein C2orf73 is a protein that in humans is encoded by the C2orf73 gene. The protein is predicted to be localized to the nucleus.
# Gene
The full gene spans a total of 53,712 base pairs and contains nine exons. The gene's location in the Human genome is on chromosome 2 at position 2p16.2 and is flanked by the genes ACYP2 and SPTBN1. There are no aliases for this gene.
# mRNA
The primary mRNA produced by the C2or73 gene is 1921 nucleotides long. There are six other mRNA isoforms produced by alternative splicing and variation in exon length.
# Protein
The protein has a molecular mass of 32,142 Daltons. There are four protein isoforms. The primary isoform (X1) is 287 amino acids long.
C2orf73 contains a short sequence motif, GDWWSH (This motif does not yet have any known function). The protein is lysine rich and leucine poor compared to the content of the average Human gene and has a predicted isoelectric point of 9.305.
# Structure
A 3D structure for C2orf73 has not yet been determined experimentally. A computational prediction made by I-TASSER is presented to the right.
The PELE tool on Biology Workbench predicts three likely α-helices and one β-strand in the protein.
# Post translational modifications
The GPS, NetPhos, MyHits and SUMOsp tools on ExPASy predict potential post-translational modifications for the protein. Six potential phosphorylation sites and one sumoylation site are predicted.
# Subcellular localization
PSORT II predicts C2orf73 to be localized to the nucleus. This is supported by the predicted presence of a sumoylation site, which is involved in nuclear cytoplasmic transport.
# Expression
GEO profiles from NCBI show that C2orf73 is weakly expressed in the following tissues in Humans: bone marrow, liver, heart, lung, brain, spinal cord, skeletal muscle, thymus, and epithelium.
# Regulation of expression
The Genomatix El Dorado tool predicts many transcription factors to have a high binding affinity in the 1100 base pairs upstream of C2orf73. Many of the transcription factors normally regulate processes such as cell development and differentiation, cell death, and the cell cycle.
# Interacting Proteins
Three proteins have been experimentally determined to interact with C2orf73 through Yeast Two-Hybrid experiments.
- FCH and Double SH3 Domains 2 (FCHSD2) - Function has not yet been defined
- Heat Shock Protein Family B Member 1 (HSPB1) - Aids cell's resistance to stress
- SH3 Domain Binding Protein 4 (SH3BP4) - Involved in endocytosis of specific cell surface receptors
# Function
The function of C2orf73 is currently not well understood by the scientific community or anyone else.
# Homology
There are no paralogs of C2orf73 in the Human genome. Orthologs are found throughout, but are limited to, the phylum Chordata (with a few exceptions in other phyla of the kingdom Animalia, like the Octopus bimaculoides). | C2orf73
Uncharacterized protein C2orf73 is a protein that in humans is encoded by the C2orf73 gene. The protein is predicted to be localized to the nucleus.
# Gene
The full gene spans a total of 53,712 base pairs and contains nine exons. The gene's location in the Human genome is on chromosome 2 at position 2p16.2 and is flanked by the genes ACYP2 and SPTBN1.[1] There are no aliases for this gene.
# mRNA
The primary mRNA produced by the C2or73 gene is 1921 nucleotides long. There are six other mRNA isoforms produced by alternative splicing and variation in exon length.[2]
# Protein
The protein has a molecular mass of 32,142 Daltons.[3] There are four protein isoforms. The primary isoform (X1) is 287 amino acids long.[4]
C2orf73 contains a short sequence motif, GDWWSH (This motif does not yet have any known function). The protein is lysine rich and leucine poor compared to the content of the average Human gene and has a predicted isoelectric point of 9.305.[5]
# Structure
A 3D structure for C2orf73 has not yet been determined experimentally. A computational prediction made by I-TASSER is presented to the right.[6]
The PELE tool on Biology Workbench predicts three likely α-helices and one β-strand in the protein.[10]
# Post translational modifications
The GPS, NetPhos, MyHits and SUMOsp tools on ExPASy[11] predict potential post-translational modifications for the protein. Six potential phosphorylation sites and one sumoylation site are predicted.
# Subcellular localization
PSORT II predicts C2orf73 to be localized to the nucleus.[12] This is supported by the predicted presence of a sumoylation site, which is involved in nuclear cytoplasmic transport.[13]
# Expression
GEO profiles from NCBI show that C2orf73 is weakly expressed in the following tissues in Humans: bone marrow, liver, heart, lung, brain, spinal cord, skeletal muscle, thymus, and epithelium.[14]
# Regulation of expression
The Genomatix El Dorado tool predicts many transcription factors to have a high binding affinity in the 1100 base pairs upstream of C2orf73. Many of the transcription factors normally regulate processes such as cell development and differentiation, cell death, and the cell cycle.[15]
# Interacting Proteins
Three proteins have been experimentally determined to interact with C2orf73 through Yeast Two-Hybrid experiments.[16]
- FCH and Double SH3 Domains 2 (FCHSD2) - Function has not yet been defined
- Heat Shock Protein Family B Member 1 (HSPB1) - Aids cell's resistance to stress
- SH3 Domain Binding Protein 4 (SH3BP4) - Involved in endocytosis of specific cell surface receptors
# Function
The function of C2orf73 is currently not well understood by the scientific community or anyone else.
# Homology
There are no paralogs of C2orf73 in the Human genome. Orthologs are found throughout, but are limited to, the phylum Chordata (with a few exceptions in other phyla of the kingdom Animalia, like the Octopus bimaculoides).[17] | https://www.wikidoc.org/index.php/C2orf73 | |
8c4790e767d60f8fcbc9973a57578c2dc1418d7e | wikidoc | C2orf81 | C2orf81
C2orf81 is a human gene encoding protein c2orf81, which is predicted to have nuclear localization.
# Gene
C2orf81's aliases are LOC388963 and hCG40743. The gene spans from bases 74,414,176 to 74,421,591 on the minus (-) strand of chromosome 2, and contains 4 exons. The coding region is 2086 base pairs, and the protein sequence contains 615 amino acids.
## Expression
The protein encoded by c2orf81 is expressed highly in testis, kidneys, and about 18 other tissues in humans. Disease states in which it is expressed include in gliomas, non-neoplasia, skin tumors, and lymphoma.
## Transcription Variants
Only a few mutations have been documented to occur in c2orf81. Three common missense mutations occur in the 3’ UTR and in the coding sequence which change serine to leucine in the protein. Nonsense mutations have been documented as well, occurring exclusively in the codon for proline.
## mRNA
The mRNA sequence contains and 2086 base pairs and 4 isoforms.
# Protein
## Properties and Composition
C2orf81 has a molecular weight of 66.6 kDa and its isoelectric point is 5.32. It contains a high amount of prolines in the human protein and most mammalian homologs, but a higher amount of glutamic acid residues in non-mammalian vertebrate homologs. C2orf81 has 4 isoforms and its most common isoform contains 615 amino acids. Isoforms 2 through 4 have 566, 520 and 588 amino acids respectively. C2orf81 is the only member of superfamily cl25621.
## Domains
Domain of unknown function (DUF) 4639 is unique to the c2orf81 protein and is conserved in eukaryotes. DUF 4639 spans from amino acid 17 to the end of the protein in human c2orf81.
## Subcellular Localization
C2orf81 is primarily predicted to be nuclear, but potentially also cytoplasmic and mitochondrial.
## Interacting proteins
C2orf81 protein is predicted to interact highly with enoyl-CoA hydratase and hydroxyacyl-CoA dehydrogenase, based on textmining and database searches. Other predicted interacting proteins are acetyl-CoA carboxylases A and B, glycine dehydrogenase, 3-oxoacid CoA transferase 2.
## Structure
The c2orf81 is composed mainly of alpha helices. It contains fewer beta pleated sheets, turns, and coils.
## Function
Despite consisting almost entirely of domain of unknown function, the c2orf81 gene has been analyzed in a study of sites prone to DNA methylation. Another study found the gene c2orf81 to overlap with other genes. Genes from its loci have been related to Alstrom syndrome, cleft palate, neurodevelopmental delays, macrocephaly, and Perry syndrome.
## Post-translational modifications
In human c2orf81, phosphorylation is expected to be undergone only in serines, but not in any threonines or tyrosines. O-linked glycosylation is predicted to occur at 3 sites toward the C-terminus. These sites are well-conserved in all homologs. C2orf81 contains one potential SUMOylation site towards the end of the protein with the sequence GKAE.
# Homology
## Paralogs
C2orf81 was found to have one paralog, Homo sapiens BAC clone RP11-523H20.
## Homologs
The c2orf81 protein is conserved highly in primates and other mammals, but less so in non-mammalian vertebrates. Its most distant homolog is in the Asian swamp eel. Below is a table showing homologs of c2orf81 and their date of divergence and percent identity to the c2orf81 protein sequence.
## Evolution
C2orf81 is has evolved quickly over time. The N-terminus of the protein has evolved less quickly than the rest of the protein. | C2orf81
C2orf81 is a human gene encoding protein c2orf81, which is predicted to have nuclear localization.
# Gene
C2orf81's aliases are LOC388963 and hCG40743.[2] The gene spans from bases 74,414,176 to 74,421,591 on the minus (-) strand of chromosome 2, and contains 4 exons.[1] The coding region is 2086 base pairs, and the protein sequence contains 615 amino acids.[3]
## Expression
The protein encoded by c2orf81 is expressed highly in testis, kidneys, and about 18 other tissues in humans.[4] Disease states in which it is expressed include in gliomas, non-neoplasia, skin tumors, and lymphoma.[5]
## Transcription Variants
Only a few mutations have been documented to occur in c2orf81. Three common missense mutations occur in the 3’ UTR and in the coding sequence which change serine to leucine in the protein. Nonsense mutations have been documented as well, occurring exclusively in the codon for proline.
## mRNA
The mRNA sequence contains and 2086 base pairs and 4 isoforms.
# Protein
## Properties and Composition
C2orf81 has a molecular weight of 66.6 kDa and its isoelectric point is 5.32.[7] It contains a high amount of prolines in the human protein and most mammalian homologs, but a higher amount of glutamic acid residues in non-mammalian vertebrate homologs.[8] C2orf81 has 4 isoforms and its most common isoform contains 615 amino acids. Isoforms 2 through 4 have 566, 520 and 588 amino acids respectively.[3] C2orf81 is the only member of superfamily cl25621.[9]
## Domains
Domain of unknown function (DUF) 4639 is unique to the c2orf81 protein and is conserved in eukaryotes.[10] DUF 4639 spans from amino acid 17 to the end of the protein in human c2orf81.
## Subcellular Localization
C2orf81 is primarily predicted to be nuclear, but potentially also cytoplasmic and mitochondrial.[11]
## Interacting proteins
C2orf81 protein is predicted to interact highly with enoyl-CoA hydratase and hydroxyacyl-CoA dehydrogenase, based on textmining and database searches.[12] Other predicted interacting proteins are acetyl-CoA carboxylases A and B, glycine dehydrogenase, 3-oxoacid CoA transferase 2.
## Structure
The c2orf81 is composed mainly of alpha helices. It contains fewer beta pleated sheets, turns, and coils.[13]
## Function
Despite consisting almost entirely of domain of unknown function, the c2orf81 gene has been analyzed in a study of sites prone to DNA methylation.[4] Another study found the gene c2orf81 to overlap with other genes.[15] Genes from its loci have been related to Alstrom syndrome, cleft palate, neurodevelopmental delays, macrocephaly, and Perry syndrome.
## Post-translational modifications
In human c2orf81, phosphorylation is expected to be undergone only in serines, but not in any threonines or tyrosines.[16] O-linked glycosylation is predicted to occur at 3 sites toward the C-terminus.[17] These sites are well-conserved in all homologs. C2orf81 contains one potential SUMOylation site towards the end of the protein with the sequence GKAE.[18]
# Homology
## Paralogs
C2orf81 was found to have one paralog, Homo sapiens BAC clone RP11-523H20.[19]
## Homologs
The c2orf81 protein is conserved highly in primates and other mammals, but less so in non-mammalian vertebrates. Its most distant homolog is in the Asian swamp eel[20]. Below is a table showing homologs of c2orf81 and their date of divergence and percent identity to the c2orf81 protein sequence.
## Evolution
C2orf81 is has evolved quickly over time.[21] The N-terminus of the protein has evolved less quickly than the rest of the protein. | https://www.wikidoc.org/index.php/C2orf81 | |
d422f10c1f1939cbbf3c63e863de6e93e73ffdb0 | wikidoc | C3orf14 | C3orf14
The human gene Chromosome 3 open reading frame 14 is a gene of uncertain function located at 3p14.2 near fragile site FRBA3—which falls between this gene and the centromere. Its protein is expected to localize to the nucleus and bind DNA. Orthologs have been identified in all of the major animal groups, minus amphibians and insects, tracing as far back as the sea anemone; indicating an origin of over 1000 mya, highlighting its importance in the animal genome.
# Gene aliases
C3orf14 is also known by the aliases LOC57415, FLJ94553 and FLJ17473. Gene orthologs found in other organisms are usually known by the name c3orf14-like, though some are known as LOC57415-like or HT021-like (protein name).
# Structure
The mRNA is composed of 6 exons, and encodes a 15007.84 kD protein known as HT021. This protein has a pre-modification isoelectric point of 5.57 and alpha helices span most of its length. Four sites of possible phosphorylation have been identified, and at least two sites of phosphorylation are conserved in all orthologs, as are two alpha helices. This protein is also predicted as a DNA binding protein. The protein may assume a tertiary structure of a coiled coil.
# Homology
Orthologs of this gene has been identified in most animal groups: mammals, monotremes, aves, reptiles, fish and invertebrates. Transcripts have not been identified in amphibians or insects; however only model organisms have been sequenced from these groups. Very recently the first ortholog in reptiles was identified in Anolis carolinensis. The amino acid structure is highly conserved through mammals, and the secondary and tertiary structure is highly conserved in all orthologs, dating as far back as 1000 mya in the sea anemone. No orthologs have been found in plants or bacteria. Below is a phylogenetic tree generated in SDSC Biology Workbench showing protein similarity among species in which C3orf14 has been identified.
# Expression
This gene was first identified in the hypothalamic-pituitary-adrenal axis (HPA axis). The GEO and EST profiles in NCBI, indicate that its expression level varies from tissue to tissue; however its reported expression is 1.2 times that of the average gene. It has highest expression in the pancreas and nervous tissue (in humans). It is underexpressed in many cancer cell lines, however this may be due to its close proximity to the tumor suppressor gene FHIT, and the chromosomal fragile site FRBA3. Breakage at this site inactivates FHIT and can lead to the loss of C3orf14.
# Function
Because C3orf14 is not ubiquitously expressed, it most likely is not a housekeeping gene. Instead, it more likely plays a role in the function of specific tissues. It seems likely then, that this gene is a transcription factor, which regulates the expression of other genes important for the function of tissues where this gene is expressed highest. | C3orf14
The human gene Chromosome 3 open reading frame 14 is a gene of uncertain function located at 3p14.2 near fragile site FRBA3—which falls between this gene and the centromere.[1] Its protein is expected to localize to the nucleus and bind DNA.[2][3] Orthologs have been identified in all of the major animal groups, minus amphibians and insects,[4] tracing as far back as the sea anemone; indicating an origin of over 1000 mya, highlighting its importance in the animal genome.
# Gene aliases
C3orf14 is also known by the aliases LOC57415, FLJ94553 and FLJ17473.[5] Gene orthologs found in other organisms are usually known by the name c3orf14-like, though some are known as LOC57415-like or HT021-like (protein name).
# Structure
The mRNA is composed of 6 exons, and encodes a 15007.84 kD protein known as HT021.[1][6] This protein has a pre-modification isoelectric point of 5.57 and alpha helices span most of its length.[6] Four sites of possible phosphorylation have been identified, and at least two sites of phosphorylation are conserved in all orthologs, as are two alpha helices. This protein is also predicted as a DNA binding protein.[3] The protein may assume a tertiary structure of a coiled coil.[7]
# Homology
Orthologs of this gene has been identified in most animal groups: mammals, monotremes, aves, reptiles, fish and invertebrates.[5] Transcripts have not been identified in amphibians or insects; however only model organisms have been sequenced from these groups. Very recently the first ortholog in reptiles was identified in Anolis carolinensis.[5] The amino acid structure is highly conserved through mammals, and the secondary and tertiary structure is highly conserved in all orthologs, dating as far back as 1000 mya in the sea anemone.[6] No orthologs have been found in plants or bacteria. Below is a phylogenetic tree generated in SDSC Biology Workbench showing protein similarity among species in which C3orf14 has been identified.[6]
# Expression
This gene was first identified in the hypothalamic-pituitary-adrenal axis (HPA axis).[8] The GEO and EST profiles in NCBI, indicate that its expression level varies from tissue to tissue; however its reported expression is 1.2 times that of the average gene.[1][9] It has highest expression in the pancreas and nervous tissue (in humans). It is underexpressed in many cancer cell lines, however this may be due to its close proximity to the tumor suppressor gene FHIT, and the chromosomal fragile site FRBA3. Breakage at this site inactivates FHIT and can lead to the loss of C3orf14.
# Function
Because C3orf14 is not ubiquitously expressed, it most likely is not a housekeeping gene. Instead, it more likely plays a role in the function of specific tissues. It seems likely then, that this gene is a transcription factor, which regulates the expression of other genes important for the function of tissues where this gene is expressed highest. | https://www.wikidoc.org/index.php/C3orf14 | |
413dd00c7d9159d6e107cbe06ed9b32d6821d0c5 | wikidoc | C3orf23 | C3orf23
Uncharacterized protein C3orf23 is a protein that in humans is encoded by the C3orf23 gene. Also known as TCAIM (T-cell activation inhibitor, mitochondrial).
# Gene
The gene is located on chromosome 3, at position 3p21.31, and is 71,333 bases long. A graphic of the image is show below in Fig.1.2 The TCAIM protein is 496 residues long and weighs 57925 Da. It exists in four different isoforms. TCAIM is highly conserved among different species of organism, but no homologies to protein families of known functions were discovered.
## Transcript
There are 8 alternatively spliced exons, which encode 4 transcript variants. The primary transcript, which is 3520 bp, is well conserved among orthologs, with the human isoform 1 having high identity with orthologous proteins. The X1 transcript contauns 11 exons, which yield a polypeptide that is 496 amino acid residues in length.
# Protein
## General Properties
The isoelectric point is significantly greater than average for human proteins (6.81).
## Structure
Shown to the right is a predicted tertiary structure of the protein. It is composed mostly of long alpha-helices with several coil regions and strands dispersed throughout the length of the protein. The ends of the protein consist of coil regions opposite the N- and C- terminal ends.
## Expression
TCAIM is moderately expressed (50-75%) in most tissues in the body. However, a study on NCBI GEO discussing the effect of disease states on TCAIM mRNA expression found that protein expression was actually elevated in HPV positive tissues compared to the HPV negative tissues. Another study found that TCAIM expression was elevated in individuals with Type 2 diabetes and insulin resistance. The expression of TCAIM seems to be contingent on the specific disease state in a variety of cases.
## Subcellular Localization
The protein contains a mitochondrial signal peptide localizing it to the mitochondrial matrix. Analysis the EXPASY localization software confirmed this finding. The high isoelectric point of the Human protein provides further evidence for the mitochondrial localization due to the high pH of the mitochondrial matrix.
## Post-translational Modifications
### Cleavage cites
The protein is initially cleaved to remove the 26 amino acids from the N-terminus. This represents a signal peptide after it is localized to the mitochondrion.
### Phosphorylation
There are a number of predicted phosphorylation sites, as see in the figure to the right. Serine residues are more likely to undergo phosphorylation than threonine or tyrosine residues.
### O-linked glycosylation
Shown to the right are a number of predicted o-linked sites. None have been experimentally determined thus far.
# Homology and Evolution
## Homologs
An alignment of Homo sapiens TCAIM and Danio rerio (Zebrafish) homologs was performed using the SDSC workbench. There is approximately 55% identity between the two orthologs, with a global alignment score of 1817. The two orthologs are consistently similar throughout the entirety of their sequences. The differences between the two genes is due seemingly random segments of non-conserved and semiconserved residues scattered throughout the two alignments. This difference may be due to the non-relatedness between the two organisms.
## Evolutionary History
TCAIM diverged much quicker than cytochrome C, but slightly slower than fibrinogen.
# Function
Not much is known about the function; it is surmised that this protein may play a role in T-cell apoptosis. TCAIM may play a role in the innate immune signaling via the mitochondria.
# Clinical Significance
A research study performed by Vogel et al. They previously found that TCAIM is highly expressed in grafts and tissues of tolerance-developing transplant patients and that the protein is localized in the mitochondria. In this study, they found that TCAIM interacts with and is regulated by CD11c(+) dendritic cells. Another article by Hendrikson et. el briefly mentions TCAIM. They found that Genetic variants in nuclear-encoded mitochondrial genes influence AIDS progression. The third article is another research that finds evidence that TCAIM (along with mitochondrial genes could be used as a marker in patients to predict whether they could accept an allograft or reject it. | C3orf23
Uncharacterized protein C3orf23 is a protein that in humans is encoded by the C3orf23 gene.[1][2] Also known as TCAIM (T-cell activation inhibitor, mitochondrial).
# Gene
The gene is located on chromosome 3, at position 3p21.31, and is 71,333 bases long. A graphic of the image is show below in Fig.1.2 The TCAIM protein is 496 residues long and weighs 57925 Da. It exists in four different isoforms. TCAIM is highly conserved among different species of organism, but no homologies to protein families of known functions were discovered.[3]
## Transcript
There are 8 alternatively spliced exons, which encode 4 transcript variants. The primary transcript, which is 3520 bp, is well conserved among orthologs, with the human isoform 1 having high identity with orthologous proteins. The X1 transcript contauns 11 exons, which yield a polypeptide that is 496 amino acid residues in length.[4]
# Protein
## General Properties
The isoelectric point is significantly greater than average for human proteins (6.81).[5]
## Structure
Shown to the right is a predicted tertiary structure of the protein. It is composed mostly of long alpha-helices with several coil regions and strands dispersed throughout the length of the protein. The ends of the protein consist of coil regions opposite the N- and C- terminal ends.
## Expression
TCAIM is moderately expressed (50-75%) in most tissues in the body.[7] However, a study on NCBI GEO discussing the effect of disease states on TCAIM mRNA expression found that protein expression was actually elevated in HPV positive tissues compared to the HPV negative tissues. Another study found that TCAIM expression was elevated in individuals with Type 2 diabetes and insulin resistance. The expression of TCAIM seems to be contingent on the specific disease state in a variety of cases.[8]
## Subcellular Localization
The protein contains a mitochondrial signal peptide localizing it to the mitochondrial matrix.[9] Analysis the EXPASY localization software[10] confirmed this finding. The high isoelectric point of the Human protein provides further evidence for the mitochondrial localization due to the high pH of the mitochondrial matrix.
## Post-translational Modifications
### Cleavage cites
The protein is initially cleaved to remove the 26 amino acids from the N-terminus. This represents a signal peptide after it is localized to the mitochondrion.[9]
### Phosphorylation
There are a number of predicted phosphorylation sites, as see in the figure to the right. Serine residues are more likely to undergo phosphorylation than threonine or tyrosine residues.
### O-linked glycosylation
Shown to the right are a number of predicted o-linked sites. None have been experimentally determined thus far.
# Homology and Evolution
## Homologs
An alignment of Homo sapiens TCAIM and Danio rerio (Zebrafish) homologs was performed using the SDSC workbench. There is approximately 55% identity between the two orthologs, with a global alignment score of 1817. The two orthologs are consistently similar throughout the entirety of their sequences. The differences between the two genes is due seemingly random segments of non-conserved and semiconserved residues scattered throughout the two alignments. This difference may be due to the non-relatedness between the two organisms.[13]
## Evolutionary History
TCAIM diverged much quicker than cytochrome C, but slightly slower than fibrinogen.[14]
# Function
Not much is known about the function; it is surmised that this protein may play a role in T-cell apoptosis. TCAIM may play a role in the innate immune signaling via the mitochondria.[15]
# Clinical Significance
A research study performed by Vogel et al. They previously found that TCAIM is highly expressed in grafts and tissues of tolerance-developing transplant patients and that the protein is localized in the mitochondria. In this study, they found that TCAIM interacts with and is regulated by CD11c(+) dendritic cells.[15] Another article by Hendrikson et. el briefly mentions TCAIM. They found that Genetic variants in nuclear-encoded mitochondrial genes influence AIDS progression.[3] The third article is another research that finds evidence that TCAIM (along with mitochondrial genes could be used as a marker in patients to predict whether they could accept an allograft or reject it.[16] | https://www.wikidoc.org/index.php/C3orf23 | |
756028a168a20497b6c063791d0f805a9b7a5c85 | wikidoc | C3orf62 | C3orf62
Chromosome 3 Open Reading Frame 62 (C3orf62), is a protein that in humans is encoded by the C3orf62 gene. C3orf62 is a glycine depleted protein relative to the amount of glycine in proteins in the rest of the genome. C3orf62 has a KKXX-like motif and is predicted to be localized in the nucleus. Expression of C3orf62 remains highest in whole blood.
# Gene
## Locus
C3orf62 is mapped to the reverse strand of chromosome 3 at 3p21.31 and spans 9.313 bases. C3orf62 starts at 49,268,597 base pairs from the terminus of the short arm (pter) and ending at 49,277,909 base pairs pter. This gene is known to have 3 exons, 4 transcripts, and 37 orthologues.
## Gene neighborhood
C3orf62 is flanked by Ubiquitin Specific Protease 4 (USP4) and Coil-Coiled Domain Containing 36 (CCDC36).
## Aliases
C3orf62 possesses the following alternate names and synonyms: CC062; FLJ43654.
# Protein
## Primary sequence
C3orf62 human protein (Q6ZUJ4) is 267 amino acids long, and has a molecular mass of 30,194 Daltons. The isoelectric point of C3orf62 is roughly 5.2.
The unmodified C3orf62 protein is a “glycine depleted protein” relative to amounts of glycine in proteins in the rest of the genome. It appears that glycine is evenly distributed throughout the C3orf62 sequence with no preference of areas to cluster in. Before post-translational modifications, C3orf62 is an acidic protein. No charge clusters are present in C3orf62, and no specific spacing of cysteine is found. The isoelectric point of C3orf62 is 5.211000.
## Domains and motifs
There are no known transmembrane domains for C3orf62. C3orf62 has a KKXX-like motif in the C-terminus meaning C3orf62 may be responsible for retrieval of endoplasmic reticulum (ER) membrane proteins from the Golgi apparatus.
## Secondary structure
Roughly 7 alpha helices are predicted for C3orf62 through Pele Protein Structure Protein Prediction and strengthened through orthologous secondary structure predictions by Ali2D.
## Subcellular localization
C3orf62 is predicted to be localized in the nucleus. The k-nearest neighbors algorithm predicts C3orf62 to be classified as follows: k=9/23; 69.6% nuclear, 13.0% mitochondrial, 13.0% cytoskeletal, 4.3% cytoplasmic.
## Expression
C3orf62 is expressed in more than 30 different tissues; highest expression is in whole blood. Specifically, highest expression of C3orf62 is in the following tissues: lung, tonsil, trachea, small intestine, mammary gland, and salivary gland. Through analysis of various microarray studies, C3orf62 is found to have consistently high expression compared to other genes tested in the datasets. C3orf62 has low expression in brain tissues.
## Post-transcriptional modifications
C3orf62 possess two post-translational modifications, both are phosphorylation sites with locations at amino acid 210 and 224. A natural variant is found at amino acid 110 (Glutamic acid (E)--> Lysine K).
It appears as though C3orf62 may have a YinOYang site at residue 115, meaning that this Threonine residue is predicted to be O-GlycNAcylated as well as phosphorylated. This site may be reversibly and dynamically modified by O-GlcNAc or Phosphate groups at different times in the cell.
# Regulation of expression
Thirteen promoters have been predicted for C3orf62.
# Transcript variants
Transcription of C3orf62 produces 5 alternatively spliced variants and 1 unspliced form. Of the four splice variants, two of them are protein coding, one is nonsense meditated decay, and one is a retained intron. QIAGEN denotes the following as transcription factor binding sites in the C3orf62 promoter: TFCP2, Pax-6, p53, MyoD, YY1, Ik-2, AREB6, IRF-7A3.
# Function
Function of C3orf62 is not currently understood by the scientific community.
## Interactions
Upwards of 12 interacting proteins have been predicted for C3orf62. Interacting proteins with the strongest confidence to interact with C3orf62 include: HAUS augmin-like complex subunit 1 (HAUS-1), Inhibitor of growth protein 5 (ING5), Thioredoxin domain-containing protein 9 (TXNDC9), and MORF4-family associated proteins (MORF4L1, MFRAP1).
Chemicals known to interact with C3orf62 include the following: Aflatoxin B1, Hydralazine, Valproic acid, and Decitabine.
## Clinical significance
Interstitial deletions of chromosome 3 are rare, and only a few patients with a microdeletion of 3p21.31 have been reported to date. Characteristic clinical features found in patients with a microdeletion of 3p21.31 include developmental delay and distinctive facial features (including arched eyebrows, hypertelorism, epicanthus, and micrognathia).
In the gene region, NCBI SNP identified 1,326 SNPS on the reverse minus strand of C3orf62. In the coding region, NCBI SNP identified 147 common SNPs.
# Homology
## Paralogs
There are no known paralogs of C3orf62.
## Orthologs
The ortholog space of C3orf62 is fairly narrow, with the majority of orthologs found in mammals. A small fraction of orthologs have also been found in the following classes: Reptila, Sarcopterygii, and Actinoptergii.
The groupings of nearly all Mammalia ortholog sequences of C3orf62 are as follows: E-value: 2e-94 to 1e-169; similarity 56-84%. Mammals in this group consist largely of primates but also include the following orders: Perissodactyla, Rodentia, Carnivora, Proboscidea, Cetartiodactyla, Cingulata, Artiodactyla, Eulipotyphla, Diselphimorphia, and Afrosoricida.
More distantly related ortholog sequences of C3orf62 include organisms from classes Reptilia, Sarcopterygii, and Actinopterygii ranging from an E-value of 8e-10 to 3e-59 with similarity of 24-39%. Organisms in this grouping consist of Testudines, Coelacanthiformes, Squamata, and Osteoglossiformes orders.
No ortholog sequences of C3orf62 were found for the following life forms: Bacteria, archaea, protist, plant, fungus, trichoplax, invertebrate, amphibian, or bird.
## Phylogeny
The most distant ortholog of C3orf62 are species of fish and amphibians. Orthologs of C3orf62 are not seen in birds, invertebrates, or bacteria. | C3orf62
Chromosome 3 Open Reading Frame 62 (C3orf62), is a protein that in humans is encoded by the C3orf62 gene. C3orf62 is a glycine depleted protein relative to the amount of glycine in proteins in the rest of the genome.[1] C3orf62 has a KKXX-like motif and is predicted to be localized in the nucleus.[2] Expression of C3orf62 remains highest in whole blood.[3]
# Gene
## Locus
C3orf62 is mapped to the reverse strand of chromosome 3 at 3p21.31 and spans 9.313 bases.[4] C3orf62 starts at 49,268,597 base pairs from the terminus of the short arm (pter) and ending at 49,277,909 base pairs pter. This gene is known to have 3 exons, 4 transcripts, and 37 orthologues.[5][3][6][7][8]
## Gene neighborhood
C3orf62 is flanked by Ubiquitin Specific Protease 4 (USP4) and Coil-Coiled Domain Containing 36 (CCDC36).
## Aliases
C3orf62 possesses the following alternate names and synonyms: CC062; FLJ43654.[6][9]
# Protein
## Primary sequence
C3orf62 human protein (Q6ZUJ4) is 267 amino acids long, and has a molecular mass of 30,194 Daltons.[5] The isoelectric point of C3orf62 is roughly 5.2.
The unmodified C3orf62 protein is a “glycine depleted protein” relative to amounts of glycine in proteins in the rest of the genome.[1] It appears that glycine is evenly distributed throughout the C3orf62 sequence with no preference of areas to cluster in. Before post-translational modifications, C3orf62 is an acidic protein. No charge clusters are present in C3orf62, and no specific spacing of cysteine is found. The isoelectric point of C3orf62 is 5.211000.[10]
## Domains and motifs
There are no known transmembrane domains for C3orf62.[9] C3orf62 has a KKXX-like motif in the C-terminus meaning C3orf62 may be responsible for retrieval of endoplasmic reticulum (ER) membrane proteins from the Golgi apparatus.[11]
## Secondary structure
Roughly 7 alpha helices are predicted for C3orf62 through Pele Protein Structure Protein Prediction and strengthened through orthologous secondary structure predictions by Ali2D.[9][12]
## Subcellular localization
C3orf62 is predicted to be localized in the nucleus.[2] The k-nearest neighbors algorithm predicts C3orf62 to be classified as follows: k=9/23; 69.6% nuclear, 13.0% mitochondrial, 13.0% cytoskeletal, 4.3% cytoplasmic.[2]
## Expression
C3orf62 is expressed in more than 30 different tissues; highest expression is in whole blood.[6][3][5] Specifically, highest expression of C3orf62 is in the following tissues: lung, tonsil, trachea, small intestine, mammary gland, and salivary gland. Through analysis of various microarray studies, C3orf62 is found to have consistently high expression compared to other genes tested in the datasets.[13] C3orf62 has low expression in brain tissues.
## Post-transcriptional modifications
C3orf62 possess two post-translational modifications, both are phosphorylation sites with locations at amino acid 210 and 224.[5] A natural variant is found at amino acid 110 (Glutamic acid (E)--> Lysine K).[8][7]
It appears as though C3orf62 may have a YinOYang site at residue 115, meaning that this Threonine residue is predicted to be O-GlycNAcylated as well as phosphorylated. This site may be reversibly and dynamically modified by O-GlcNAc or Phosphate groups at different times in the cell.[14]
# Regulation of expression
Thirteen promoters have been predicted for C3orf62.[15]
# Transcript variants
Transcription of C3orf62 produces 5 alternatively spliced variants and 1 unspliced form. Of the four splice variants, two of them are protein coding, one is nonsense meditated decay, and one is a retained intron.[6] QIAGEN denotes the following as transcription factor binding sites in the C3orf62 promoter: TFCP2, Pax-6, p53, MyoD, YY1, Ik-2, AREB6, IRF-7A3.[3]
# Function
Function of C3orf62 is not currently understood by the scientific community.
## Interactions
Upwards of 12 interacting proteins have been predicted for C3orf62.[16][17][18] Interacting proteins with the strongest confidence to interact with C3orf62 include: HAUS augmin-like complex subunit 1 (HAUS-1), Inhibitor of growth protein 5 (ING5), Thioredoxin domain-containing protein 9 (TXNDC9), and MORF4-family associated proteins (MORF4L1, MFRAP1).
Chemicals known to interact with C3orf62 include the following: Aflatoxin B1, Hydralazine, Valproic acid, and Decitabine.[6]
## Clinical significance
Interstitial deletions of chromosome 3 are rare, and only a few patients with a microdeletion of 3p21.31 have been reported to date. Characteristic clinical features found in patients with a microdeletion of 3p21.31 include developmental delay and distinctive facial features (including arched eyebrows, hypertelorism, epicanthus, and micrognathia).[19][20][21]
In the gene region, NCBI SNP identified 1,326 SNPS on the reverse minus strand of C3orf62.[22] In the coding region, NCBI SNP identified 147 common SNPs.
# Homology
## Paralogs
There are no known paralogs of C3orf62.[23]
## Orthologs
The ortholog space of C3orf62 is fairly narrow, with the majority of orthologs found in mammals.[23] A small fraction of orthologs have also been found in the following classes: Reptila, Sarcopterygii, and Actinoptergii.
The groupings of nearly all Mammalia ortholog sequences of C3orf62 are as follows: E-value: 2e-94 to 1e-169; similarity 56-84%. Mammals in this group consist largely of primates but also include the following orders: Perissodactyla, Rodentia, Carnivora, Proboscidea, Cetartiodactyla, Cingulata, Artiodactyla, Eulipotyphla, Diselphimorphia, and Afrosoricida.[23]
More distantly related ortholog sequences of C3orf62 include organisms from classes Reptilia, Sarcopterygii, and Actinopterygii ranging from an E-value of 8e-10 to 3e-59 with similarity of 24-39%.[23] Organisms in this grouping consist of Testudines, Coelacanthiformes, Squamata, and Osteoglossiformes orders.
No ortholog sequences of C3orf62 were found for the following life forms: Bacteria, archaea, protist, plant, fungus, trichoplax, invertebrate, amphibian, or bird.
## Phylogeny
The most distant ortholog of C3orf62 are species of fish and amphibians. Orthologs of C3orf62 are not seen in birds, invertebrates, or bacteria.[23] | https://www.wikidoc.org/index.php/C3orf62 | |
65c0f24a7518ef37e8da020ff872530379b7f367 | wikidoc | C3orf70 | C3orf70
C3orf70 also known as Chromosome 3 Open Reading Frame 70, is a 250aa protein in humans that is encoded by the C3orf70 gene. The protein encoded is predicted to be a nuclear protein; however, its exact function is currently unknown. C3orf70 can be identified with known aliases: Chromosome 3 Open Reading Frame 70, AK091454, UPF0524, and LOC285382.
# Gene
In humans, C3orf70 is located on the reverse strand of Chromosome 3 at 3q27.2 (see Figure 1). This identifies its location starting 184,795,838 base pairs and ending 184,870,802 base pairs from PTER, the terminus of the short arm, on chromosome 3. C3orf70 spans 74,964 bases containing two exons and two introns.
# mRNA
The transcribed mRNA is a 5,901 base pair transcript. C3orf70 consists of one known splice variant with two exons of 388 base pairs and 5,512 base pairs respectively (see Figure 2); location of junction occurs at 67aa. A single 5’ cap and three possible 3’ polyadenylation signals have been identified.
# Protein
## Composition
The translated protein is a 250 amino acid product. The precursor protein has been predicted with a molecular weight of 27.8kdal and an isoelectric point of 4.67. With 33 serines and 8 glysines, the C3orf70 protein is both Serine rich and Glycine poor.
## Domains
C3orf70 protein has no known signal peptides or domains.
# Homology
C3orf70 has no known paralogs in humans; however C3orf70 has conserved homologs, see Figure 3. Highly conserved across species excluding invertebrates, plants, fungi, and bacteria, C3orf70 shows a moderate rate of evolution, see Figure 4 and 5.
- Figure 3: Compiled data for select orthologs of C3orf70 across species
Figure 3: Compiled data for select orthologs of C3orf70 across species
- Figure 4: C3orf70 Homolog Protein Divergence from Homo sapiens. Color identification specific to species (shown in Figure 3). Time of divergence calculated by timetree.org. Non-identity calculated based on (1-NCBI sequence identity).
Figure 4: C3orf70 Homolog Protein Divergence from Homo sapiens. Color identification specific to species (shown in Figure 3). Time of divergence calculated by timetree.org. Non-identity calculated based on (1-NCBI sequence identity).
- Figure 5: Divergence rate of C3orf70 with respect to Cytochrome C and Fibrinogen displaying a moderate to slow rate of divergence.
Figure 5: Divergence rate of C3orf70 with respect to Cytochrome C and Fibrinogen displaying a moderate to slow rate of divergence.
# Regulation
## Transcription
### Promoter
There is only one known promoter predicted by Genomatix for the C3orf70 protein located on the minus strand of chromosome 3 at location 184870702-184871302bp, therefore identified as 600bp in length. High mammalian conservation was observed for the identified promoter sequence.
### Transcription factors
Through the use of Genomatix, a table was generated of the top 20 transcription factors and their binding sites in the C3orf70 promoter (see Figure 6).
## Translation
### Post-translational modifications
Utilizing NetPhos, a total of 25 phosphorylation sites have been predicted (20 Serines, 3 Threonines, and 2 Tyrosines) which occur throughout the protein indicating an intracellular localization. Figure 7 pinpoints the location of the 25 potential phosphorylation sites. Additionally, two N-myrisolation sites were predicted at amino acid position 40-45 and 210-215 indicating a possible N-terminus and C-terminus membrane anchor region. There are also 28 potential missense mutations in the human C3orf70.
### Subcellular localization
PSORT II indicates the subcellular localization of C3orf70 is in the nucleus. In addition to this, following SDSC's Biology Workbench's SAPS kNN-Prediction, the C3orf70 protein for humans has a 60.9% likelihood to end up in the nuclear region of a cell, as determined by the amino acid make-up of C3orf70. Homologs including chimp, mouse, alligator, and zebrafish conclude the same nuclear region with a >60% likelihood. A nuclear localization site has not been identified in the C3orf70 sequence.
# Expression
From Unigene's EST cDNA tissue abundance display (see Figure 8), C3orf70 is non-ubiquitously expressed and has relatively low expression levels with slightly higher expression levels seen in the brain. Also, microarray data profile GDS426 (see Figure 9) showing the expression of C3orf70 across normal tissues displays a notably high presence in the brain, spinal cord, and prostate tissue.
## Function and further reading
The function of C3orf70 is unknown. It is suggested to be a nuclear protein that plays a role in neurological development. Additional avenues of research pertaining to the C3orf70 gene include:
There is a patent that identified genes associated with midbrain dopamine neurons for engraftment by looking at the differentiation of hESC and/or hiPSC in floor plate midbrain progenitor cells. C3orf70 was found to have a fold-change of 2.45, which was not determined significant in experimentation
A publication was discovered through multiple sources that linked the C3orf70 gene to a “Genome-wide association study of major depressive disorder”.
A microdeletion has been identified from 3q26.33-3q27.2. Mandrille et al. associates this discovered microdeletion with a possible clinical syndrome characterized by clinical features related to brain development. | C3orf70
C3orf70 also known as Chromosome 3 Open Reading Frame 70, is a 250aa protein in humans that is encoded by the C3orf70 gene. The protein encoded is predicted to be a nuclear protein; however, its exact function is currently unknown.[1] C3orf70 can be identified with known aliases: Chromosome 3 Open Reading Frame 70, AK091454, UPF0524, and LOC285382.[1][2]
# Gene
In humans, C3orf70 is located on the reverse strand of Chromosome 3 at 3q27.2 (see Figure 1).[3] This identifies its location starting 184,795,838 base pairs and ending 184,870,802 base pairs from PTER, the terminus of the short arm, on chromosome 3. C3orf70 spans 74,964 bases containing two exons and two introns.
# mRNA
The transcribed mRNA is a 5,901 base pair transcript. C3orf70 consists of one known splice variant with two exons of 388 base pairs and 5,512 base pairs respectively (see Figure 2); location of junction occurs at 67aa[C].[1] A single 5’ cap and three possible 3’ polyadenylation signals have been identified.[1]
# Protein
## Composition
The translated protein is a 250 amino acid product. The precursor protein has been predicted with a molecular weight of 27.8kdal and an isoelectric point of 4.67.[4] With 33 serines and 8 glysines, the C3orf70 protein is both Serine rich and Glycine poor.[4]
## Domains
C3orf70 protein has no known signal peptides or domains.
# Homology
C3orf70 has no known paralogs in humans; however C3orf70 has conserved homologs, see Figure 3. Highly conserved across species excluding invertebrates, plants, fungi, and bacteria, C3orf70 shows a moderate rate of evolution, see Figure 4 and 5.[5]
- Figure 3: Compiled data for select orthologs of C3orf70 across species
Figure 3: Compiled data for select orthologs of C3orf70 across species
- Figure 4: C3orf70 Homolog Protein Divergence from Homo sapiens. Color identification specific to species (shown in Figure 3). Time of divergence calculated by timetree.org. Non-identity calculated based on (1-NCBI sequence identity).
Figure 4: C3orf70 Homolog Protein Divergence from Homo sapiens. Color identification specific to species (shown in Figure 3). Time of divergence calculated by timetree.org. Non-identity calculated based on (1-NCBI sequence identity).
- Figure 5: Divergence rate of C3orf70 with respect to Cytochrome C and Fibrinogen displaying a moderate to slow rate of divergence.
Figure 5: Divergence rate of C3orf70 with respect to Cytochrome C and Fibrinogen displaying a moderate to slow rate of divergence.
# Regulation
## Transcription
### Promoter
There is only one known promoter predicted by Genomatix for the C3orf70 protein located on the minus strand of chromosome 3 at location 184870702-184871302bp, therefore identified as 600bp in length.[6] High mammalian conservation was observed for the identified promoter sequence.
### Transcription factors
Through the use of Genomatix, a table was generated of the top 20 transcription factors and their binding sites in the C3orf70 promoter (see Figure 6).[6]
## Translation
### Post-translational modifications
Utilizing NetPhos, a total of 25 phosphorylation sites have been predicted (20 Serines, 3 Threonines, and 2 Tyrosines) which occur throughout the protein indicating an intracellular localization.[7] Figure 7 pinpoints the location of the 25 potential phosphorylation sites. Additionally, two N-myrisolation sites were predicted at amino acid position 40-45 and 210-215 indicating a possible N-terminus and C-terminus membrane anchor region.[8] There are also 28 potential missense mutations in the human C3orf70.[9]
### Subcellular localization
PSORT II indicates the subcellular localization of C3orf70 is in the nucleus.[10] In addition to this, following SDSC's Biology Workbench's SAPS kNN-Prediction, the C3orf70 protein for humans has a 60.9% likelihood to end up in the nuclear region of a cell, as determined by the amino acid make-up of C3orf70.[4] Homologs including chimp, mouse, alligator, and zebrafish conclude the same nuclear region with a >60% likelihood.[10] A nuclear localization site has not been identified in the C3orf70 sequence.
# Expression
From Unigene's EST cDNA tissue abundance display (see Figure 8), C3orf70 is non-ubiquitously expressed and has relatively low expression levels with slightly higher expression levels seen in the brain.[11] Also, microarray data profile GDS426 (see Figure 9) showing the expression of C3orf70 across normal tissues displays a notably high presence in the brain, spinal cord, and prostate tissue.[12]
## Function and further reading
The function of C3orf70 is unknown. It is suggested to be a nuclear protein that plays a role in neurological development. Additional avenues of research pertaining to the C3orf70 gene include:
There is a patent that identified genes associated with midbrain dopamine neurons for engraftment by looking at the differentiation of hESC and/or hiPSC in floor plate midbrain progenitor cells. C3orf70 was found to have a fold-change of 2.45, which was not determined significant in experimentation [13]
A publication was discovered through multiple sources that linked the C3orf70 gene to a “Genome-wide association study of major depressive disorder”.[14]
A microdeletion has been identified from 3q26.33-3q27.2.[15] Mandrille et al. associates this discovered microdeletion with a possible clinical syndrome characterized by clinical features related to brain development. | https://www.wikidoc.org/index.php/C3orf70 | |
284e5c79cd311766f16e9d0b2bc3c525607e3bbe | wikidoc | C4orf21 | C4orf21
C4orf21 (Chromosome 4 open reading frame 21) is a protein in humans that is encoded by the C4orf21 gene that has uncharacterised function and a weight of 236.6 kDa. The encoded protein of this gene has been linked with alcohol dependence. This gene shows relatively low expression in most human tissues, with increased expression in situations of chemical dependence. C4orf21 is orthologous to nearly all kingdoms of Eukarya. Functional domains of this protein link it to a series of helicases, most notably the AAA_12 and AAA_11 domains.
# Gene
The entire gene is 97,663 base pairs long and has an unprocessed mRNA that is 6,740 nucleotides in length. It consists of 28 exons that encode for a 2104 amino acid protein. 12 splice variants exist for C4orf21.
## Locus
C4orf21 is located on the fourth chromosome on the 4q25 position near the LARP7 gene. It is encoded for on the minus strand.
# Homology and evolution
## Homologous domains
C4orf21 contains a DUF2439 domain (domain of unknown function), zf-GRF domain, and AAA_11 and an AAA_12 domain (ATPases associated with diverse cellular activities). DUF domains are involved in telomere maintenance and meiotic segregation. AAA_11 and AAA_12 contain a P-loop motif which are involved in conjugative transfer proteins. Other helicase domains are also present in c4orf21 orthologs.
## Paralogs
There are 9 moderately-related proteins in humans that are paralogous to the ATP-dependent helicase containing domains in the C-terminus of c4orf21 after the 1612th amino acid. A majority of these proteins are in the RNA helicase family. There are no known paralogs to the large N-terminal portion of the protein.
## Orthologs
Complete orthologs of the c4orf21 gene are found in mammalia. The helicase domain containing C-terminus portion of the gene is conserved across Eukarya.
# Protein
## Primary sequence
C4orf21 is 236.6 kDa.
## Post-translational modifications
C4orf21 has experimentally determined phosphorylation sites at the Y38, S137, S140, S325, and S864 positions.
## Secondary structure
A weak transmembrane domain is predicted in the TMHMM server with one loop in the C-terminus of the protein prior to the helicase core. This domain contains both ends outside of a membrane.
## Tertiary domains and quaternary structure
C4orf21 has related structures to Upf1, a paralog. These structures have the capability to bind zinc ions and mRNA.
# Function and biochemistry
The function of c4orf21 is unknown. Given this, the paralogs to the helicase core of the gene are associated with translation, transcription, nonsense-mediated mRNA decay, RNA decay, miRNA processing, RISC assembly, and pre-mRNA splicing. These paralogs operate under a SPF1 RNA helicase motif.
Mov10, a paralog, and probable RNA helicase is required for RNA-mediated gene silencing by the RNA-induced silencing complex (RISC). It is also required for both miRNA-mediated translational repression and miRNA-mediated cleavage of complementary mRNAs by RISC, and for RNA-directed transcription and replication of the human hepatitis delta virus (HDV). Mov10 nteracts with small capped HDV RNAs derived from genomic hairpin structures that mark the initiation sites of RNA-dependent HDV RNA transcription.
# Expression
Expression is relatively low for c4orf21 compared to other proteins. Expression of c4orf21 is slightly elevated compared to its average expression in tissue in the hematopoietic and lymphatic systems, and is above average in the brain also. Lower averages exist in liver, pharynx, and skin tissue.
## Transcription factor interactions
The transcriptional start site for c4orf21 aligns best with ATF, CREB, deltaCREB, E2F, and E2F-1 transcription factor binding sites.
# Interacting proteins
C4orf21 shows predicted protein interaction with its AQR, DNA2, IGHMBP2, LOC91431, and SETX paralogs.
# Clinical significance
C4orf21 has been previously linked to alcohol dependence (where genes linked to this disorder are also linked to alcoholism and other psychological and personality disorder). Given this, expression of the gene in the liver and brain are particularly interesting. Upon examination of variable GEO profiles, there were many related to Hepatitis and other disorders of the liver. The best correlative studies were those in relation to liver transplant failure. The link to alcohol dependence provides a strong connection to dependence to other chemical substances such as nicotine through analysis of lymphoblast cells. C4orf21 showed significantly increased expression in those who were nicotine dependent versus a control group of non-smokers. Upregulation of c4orf21 was also present in certain cancer expression data sets.
A paralog of c4orf21 was found to inhibit HIV-1 Replication at multiple stages. Mov10 is involved in the biological processes of RNA-mediated gene silencing, transcription, transcription regulation and has hydrolase and helicase activity through ATP and RNA binding. | C4orf21
C4orf21 (Chromosome 4 open reading frame 21) is a protein in humans that is encoded by the C4orf21 gene that has uncharacterised function and a weight of 236.6 kDa.[1] The encoded protein of this gene has been linked with alcohol dependence.[2] This gene shows relatively low expression in most human tissues, with increased expression in situations of chemical dependence. C4orf21 is orthologous to nearly all kingdoms of Eukarya. Functional domains of this protein link it to a series of helicases, most notably the AAA_12 and AAA_11 domains.
# Gene
The entire gene is 97,663 base pairs long and has an unprocessed mRNA that is 6,740 nucleotides in length. It consists of 28 exons that encode for a 2104 amino acid protein. 12 splice variants exist for C4orf21.
## Locus
C4orf21 is located on the fourth chromosome on the 4q25 position near the LARP7 gene. It is encoded for on the minus strand.
# Homology and evolution
## Homologous domains
C4orf21 contains a DUF2439 domain (domain of unknown function), zf-GRF domain, and AAA_11 and an AAA_12 domain (ATPases associated with diverse cellular activities). DUF domains are involved in telomere maintenance and meiotic segregation. AAA_11 and AAA_12 contain a P-loop motif which are involved in conjugative transfer proteins. Other helicase domains are also present in c4orf21 orthologs.
## Paralogs
There are 9 moderately-related proteins in humans that are paralogous to the ATP-dependent helicase containing domains in the C-terminus of c4orf21 after the 1612th amino acid. A majority of these proteins are in the RNA helicase family. There are no known paralogs to the large N-terminal portion of the protein.
## Orthologs
Complete orthologs of the c4orf21 gene are found in mammalia. The helicase domain containing C-terminus portion of the gene is conserved across Eukarya.
# Protein
## Primary sequence
C4orf21 is 236.6 kDa.
## Post-translational modifications
C4orf21 has experimentally determined phosphorylation sites at the Y38, S137, S140, S325, and S864 positions.
## Secondary structure
A weak transmembrane domain is predicted in the TMHMM server with one loop in the C-terminus of the protein prior to the helicase core. This domain contains both ends outside of a membrane.
## Tertiary domains and quaternary structure
C4orf21 has related structures to Upf1, a paralog. These structures have the capability to bind zinc ions and mRNA.
# Function and biochemistry
The function of c4orf21 is unknown. Given this, the paralogs to the helicase core of the gene are associated with translation, transcription, nonsense-mediated mRNA decay, RNA decay, miRNA processing, RISC assembly, and pre-mRNA splicing.[3] These paralogs operate under a SPF1 RNA helicase motif.[4]
Mov10, a paralog, and probable RNA helicase is required for RNA-mediated gene silencing by the RNA-induced silencing complex (RISC). It is also required for both miRNA-mediated translational repression and miRNA-mediated cleavage of complementary mRNAs by RISC, and for RNA-directed transcription and replication of the human hepatitis delta virus (HDV). Mov10 nteracts with small capped HDV RNAs derived from genomic hairpin structures that mark the initiation sites of RNA-dependent HDV RNA transcription.
# Expression
Expression is relatively low for c4orf21 compared to other proteins. Expression of c4orf21 is slightly elevated compared to its average expression in tissue in the hematopoietic and lymphatic systems, and is above average in the brain also. Lower averages exist in liver, pharynx, and skin tissue.[5]
## Transcription factor interactions
The transcriptional start site for c4orf21 aligns best with ATF, CREB, deltaCREB, E2F, and E2F-1 transcription factor binding sites.
# Interacting proteins
C4orf21 shows predicted protein interaction with its AQR, DNA2, IGHMBP2, LOC91431, and SETX paralogs.[6]
# Clinical significance
C4orf21 has been previously linked to alcohol dependence[2] (where genes linked to this disorder are also linked to alcoholism and other psychological and personality disorder).[7] Given this, expression of the gene in the liver and brain are particularly interesting. Upon examination of variable GEO profiles, there were many related to Hepatitis and other disorders of the liver. The best correlative studies were those in relation to liver transplant failure.[8][9] The link to alcohol dependence provides a strong connection to dependence to other chemical substances such as nicotine through analysis of lymphoblast cells. C4orf21 showed significantly increased expression in those who were nicotine dependent versus a control group of non-smokers.[9][10] Upregulation of c4orf21 was also present in certain cancer expression data sets.
A paralog of c4orf21 was found to inhibit HIV-1 Replication at multiple stages. Mov10 is involved in the biological processes of RNA-mediated gene silencing, transcription, transcription regulation and has hydrolase and helicase activity through ATP and RNA binding.[11] | https://www.wikidoc.org/index.php/C4orf21 | |
6bfc92fc5e6e1d9a27851debaa85b054fdf0439f | wikidoc | C4orf29 | C4orf29
Chromosome 4 open reading frame 29 (C4orf29) is a protein that in Homo sapiens is encoded by the C4orf29 gene.
# Gene
C4orf29 is found on the positive strand of the human genome at 4q28.2. It is 74.4 kbp. The gene contains 17 exons. The longest mRNA transcript is composed of 13 exons and is 2200 base pairs.
# Homology
## Orthologs
Many orthologs to human C4orf29 have been discovered, with the most distant ortholog with high (over 90%) coverage is found in rice Oryza sativa. The protein is not found in fungi. Bacteria of the order Myxobacteria and genus Chitinimonas contain orthologous regions to the C4orf29 protein. The few bacterial homologs indicate a horizontal gene transfer event. The domain of unknown function, DUF2048, is conserved throughout orthologs.
# Protein
C4orf29 codes a 414 amino acid sequence of 46.9 kDa in humans. The predicted isoelectric point is 9.37. The domain of unknown function, DUF2048, is found from amino acid residues 25 to 414 in the precursor C4orf29 protein. This domain is part of the alpha/beta hydrolase superfamily, which comprises enzymes that catalyze fat metabolism. Predicted post-translational modifications include glycosylation at residues Ser287 and Ser319 and sumoylation at the motifs Phe240 to Gly243, Ala377 to Asp340, and Phe408 to Gly411.
# Expression
The protein product of C4orf29 in humans is predicted to be a secreted product. It is ubiquitously expressed at low to moderate levels. In humans, the protein is found at high levels the digestive tract and parathyroid gland. The homologous mouse protein 3110057O12Rik is expressed at high levels in the granule layer of the cerebellum.
# Clinical significance
C4orf29 contains highly variable numbers of Alu repeats. A low number of Alu repeats in the human C4orf29 protein is associated with increase prevalence of hepatocellular carcinoma (HCC) in Asian populations. This information is used as a genetic marker to determine genetic risk of HCC.
Swine muscle transcriptome analysis indicates high expression of C4orf29 in swine with extreme low levels of fatty acid composition. | C4orf29
Chromosome 4 open reading frame 29 (C4orf29) is a protein that in Homo sapiens is encoded by the C4orf29 gene.[1]
# Gene
C4orf29 is found on the positive strand of the human genome at 4q28.2. It is 74.4 kbp. The gene contains 17 exons.[2] The longest mRNA transcript is composed of 13 exons and is 2200 base pairs.[1]
# Homology
## Orthologs
Many orthologs to human C4orf29 have been discovered, with the most distant ortholog with high (over 90%) coverage is found in rice Oryza sativa.[4] The protein is not found in fungi. Bacteria of the order Myxobacteria and genus Chitinimonas contain orthologous regions to the C4orf29 protein. The few bacterial homologs indicate a horizontal gene transfer event. The domain of unknown function, DUF2048, is conserved throughout orthologs.
# Protein
C4orf29 codes a 414 amino acid sequence of 46.9 kDa in humans. The predicted isoelectric point is 9.37.[6] The domain of unknown function, DUF2048, is found from amino acid residues 25 to 414 in the precursor C4orf29 protein.[7] This domain is part of the alpha/beta hydrolase superfamily, which comprises enzymes that catalyze fat metabolism. Predicted post-translational modifications include glycosylation at residues Ser287 and Ser319 [8] and sumoylation[9] at the motifs Phe240 to Gly243, Ala377 to Asp340, and Phe408 to Gly411.
# Expression
The protein product of C4orf29 in humans is predicted to be a secreted product. It is ubiquitously expressed at low to moderate levels.[10] In humans, the protein is found at high levels the digestive tract and parathyroid gland.[11] The homologous mouse protein 3110057O12Rik is expressed at high levels in the granule layer of the cerebellum.[12]
# Clinical significance
C4orf29 contains highly variable numbers of Alu repeats.[13] A low number of Alu repeats in the human C4orf29 protein is associated with increase prevalence of hepatocellular carcinoma (HCC) in Asian populations. This information is used as a genetic marker to determine genetic risk of HCC.[14]
Swine muscle transcriptome analysis indicates high expression of C4orf29 in swine with extreme low levels of fatty acid composition.[15] | https://www.wikidoc.org/index.php/C4orf29 | |
50e0b6853d80268778d4ef20f12e1600c36d1eee | wikidoc | C57BL/6 | C57BL/6
C57BL/6, often referred to as "C57 black 6" or just "black 6" is a common inbred strain of lab mouse. It is probably the most widely used "genetic background" for genetically modifed mice for use as models of human disease. They are the most widely used lab mouse strain, due to the availability of congenic strains, easy breeding, robustness, and their relationship to GM models, making them ideal controls.
# Appearance and behavior
Dark brown, nearly black, coat. Easily irritable temperament. They have a tendency to bite, and cannot be handled like a typical pet mouse or even more docile laboratory strains such as BALB-C. They also have a tendency (shared with other mouse strains) to "overgroom" their cage-mates, resulting in large bald patches on their backs.
# C57BL/6 as a "Th1 responder"
C57BL/6 has certain immunophenotypes that distinguish it from other inbred strains like BALB/c. For example the immunological response to the same pathogen in C57BL/6 mice is often of an opposite spectrum compared to BALBb/c mice, namely C57BL/6 shows Th1 and BALB/c shows Th2 response in response to intracellular pathogen Leishmania major, where a Th1 response results in a resistant ie healer phenotype (since the pathogen is intracellular), whereas a Th2 response results in a susceptible (nonhealer) phenotype.
Though this trait had been observed in these two strains since 1988, in an article published in 2000 by Mills et al. these observations were systematized and generalized to other strains of mice. Even without biasing towards Th1 or Th2 by priming through infection, the strains differ in their macrophages' ability to be activated, as measured from their arginine metabolic programs when stimulated by Interferon gamma or LPS or both:
- M-1 macrophages from typical Th1 responders:C57BL/6 or B10.D2 mice, preferentially produce NO by action of iNOS
- M-2 macrophages from typical Th2 responders: DBA or BALB/c mice), preferentially produce ornithine and urea by action of argininase
# Response to diseases
Plasmodium (malaria)
- P. yoelii YM = lethal
- P. yoelii 17XL = lethal
- P. yoelii 17XNL = "non-lethal" (though up to 50% mortality is not unusual)
- P. berghii = lethal (with cerebral malaria)
- P. vinkii = lethal
- P. chabaudi AS = non-lethal | C57BL/6
Template:Animal testing
C57BL/6, often referred to as "C57 black 6" or just "black 6" is a common inbred strain of lab mouse. It is probably the most widely used "genetic background" for genetically modifed mice for use as models of human disease. They are the most widely used lab mouse strain, due to the availability of congenic strains, easy breeding, robustness, and their relationship to GM models, making them ideal controls.
# Appearance and behavior
Dark brown, nearly black, coat. Easily irritable temperament. They have a tendency to bite, and cannot be handled like a typical pet mouse or even more docile laboratory strains such as BALB-C. They also have a tendency (shared with other mouse strains) to "overgroom" their cage-mates, resulting in large bald patches on their backs.
# C57BL/6 as a "Th1 responder"
C57BL/6 has certain immunophenotypes that distinguish it from other inbred strains like BALB/c. For example the immunological response to the same pathogen in C57BL/6 mice is often of an opposite spectrum compared to BALBb/c mice, namely C57BL/6 shows Th1 and BALB/c shows Th2 response in response to intracellular pathogen Leishmania major, where a Th1 response results in a resistant ie healer phenotype (since the pathogen is intracellular), whereas a Th2 response results in a susceptible (nonhealer) phenotype.
Though this trait had been observed in these two strains since 1988, in an article published in 2000 by Mills et al.[1] these observations were systematized and generalized to other strains of mice. Even without biasing towards Th1 or Th2 by priming through infection, the strains differ in their macrophages' ability to be activated, as measured from their arginine metabolic programs when stimulated by Interferon gamma or LPS or both:
- M-1 macrophages from typical Th1 responders:C57BL/6 or B10.D2 mice, preferentially produce NO by action of iNOS
- M-2 macrophages from typical Th2 responders: DBA or BALB/c mice), preferentially produce ornithine and urea by action of argininase
# Response to diseases
Plasmodium (malaria)
- P. yoelii YM = lethal
- P. yoelii 17XL = lethal
- P. yoelii 17XNL = "non-lethal" (though up to 50% mortality is not unusual)
- P. berghii = lethal (with cerebral malaria)
- P. vinkii = lethal
- P. chabaudi AS = non-lethal | https://www.wikidoc.org/index.php/C57BL/6 | |
0bd32e7095a65dbe72c0e22594132319362bb82e | wikidoc | C5orf36 | C5orf36
C5orf36 is a protein that in humans is encoded by the gene of the same name, located on chromosome 5, 5q15. It is a possible risk factor in Type II Diabetes, and associated with high levels of glucose in the blood. It is a relatively fast mutating gene, compared to other coding genes. There is however one region which is highly conserved across the species that have the gene, known as DUF4495. It is predicted to be a protein that travels between the nucleus and the cytoplasm.
# General information
C5orf36 is gene that appears to be a genetic factor that increases the risk of Type II Diabetes, possibly by increasing the level of blood glucose levels. It has also been identified as a possible oncogene. C5orf36 has one common alias KIAA0825. The gene is about 478 kb long and contains 22 exons. It produces 10 different variants: 9 alternatively spliced, and one un-spliced version. The longest experimentally confirmed mRNA is 7240 bp long and produces a protein 1275 amino acids long. The protein is predicted to weigh about 147.8kDal. It has orthologs in most animals including Aplysia californica, but is not found outside animals with the possible exception of Plasmodiophora brassicae.
# Protein information
The protein has a predicted weight of 147.8 kDal. It does not contain a known nuclear localization signal but does contain a nuclear export signal. The subcellular localization for the protein is predicted to be the nucleus and the cytoplasm. This suggests that the protein might shuttle back and forth across the nuclear membrane.
## Secondary structure
Several programs suggest that the secondary structure of the protein is mainly helices with only a few beta sheets. Analysis of protein composition also suggests that the protein has relatively low levels of glycine. This could suggest a fairly rigid structure relative to other proteins.
The tertiary structure is harder to predict due to the size of the protein, partially due to its size. The 3-D structure shown shows a prediction made by I-TASSER. This is a possible strture with a C-score of -1.06 on a scale from -5 to 1 (in which the higher the number the greater the confidence). This predicted structure indicates there are two main parts, and it is possible they interact depending on the state of the protein (e.g. whether or not it's phosphorylated).
# Expression
The mRNA for C5orf36 is expressed at relatively low rates in comparison to other mRNAs. The protein however is expressed at relatively high rates, especially in parts of the brain as well as adrenal glands and the thyroid. This would suggest that the protein is not readily degraded and remains in the cell for long periods of time, such that continuous transcription of the DNA into mRNA is unnecessary. In an expression profile done of the peripheral blood of patients with B-lymphocytic leukemia C5orf36 has slightly higher levels in patients with chronic B-lymphocytic leukemia as compared to the healthy patients. Another expression profile shows that C5orf36 is expressed at lower levels in patients with Type II Diabetes compared with healthy patients. No current finding suggest that there is alternative expression of different isoforms in different tissues.
# Regulation
Analysis of the promoter offers some insight into the expression of C5orf36. One possible regulator found is the NeuroD1 transcription factor. This factor is an important regulator for the insulin gene, and a mutation in this gene can lead to Type II diabetes. This could explain why C5orf36 is expressed at lower levels in patients with Type II diabetes. Another possible transcription factor is the Myeloid zinc finger 1 factor, which is tied to myeloid leukemia, because it delays apoptosis of cells in the presence of retinoic acid. There are also several places where Vertebrate SMAD family transcription factors can bind. These transcription factors are thought to be responsible for nucleocytoplasmic dynamics. This means that these SMAD transcription factors could effect C5orf36, because subcellular localization suggests it shuttles across the nuclear envelope.
# Function
There are two proteins found to interact with C5orf36. One is One is Interleukin enhancer-binding factor 3. ILF3 is a factor that complexes with other proteins and regulates gene expression and stabilizes mRNAs. The other is the Amyloid-beta precursor protein. This protein is an integral membrane protein found most commonly in the synapses of neurons. Neither of these proteins is well enough understood to indicate for certain the role of C5orf36 in human cells. They however suggest that C5orf36 could serve a variety of roles in different parts of the cell.
# Orthology
C5orf36 orthologs can be found in virtually all animals, but cannot be found in plants, bacteria, or protozoa. It is mostly highly conserved in vertebrates especially mammals, but genes that contain region similar to DUF4495 region can be found in California sea hare, generally one of the most simple animal. The size especially in mammals is well conserved sticking very close to between 1250 and 1300 amino acids long. This suggests that the protein wraps around on itself forming important structures for its function.
There were no paralogs found of the gene C5orf36 in humans or in any other species. | C5orf36
C5orf36 is a protein that in humans is encoded by the gene of the same name, located on chromosome 5, 5q15. It is a possible risk factor in Type II Diabetes, and associated with high levels of glucose in the blood. It is a relatively fast mutating gene, compared to other coding genes. There is however one region which is highly conserved across the species that have the gene, known as DUF4495. It is predicted to be a protein that travels between the nucleus and the cytoplasm.
# General information
C5orf36 is gene that appears to be a genetic factor that increases the risk of Type II Diabetes, possibly by increasing the level of blood glucose levels.[1] It has also been identified as a possible oncogene.[2] C5orf36 has one common alias KIAA0825. The gene is about 478 kb long and contains 22 exons. It produces 10 different variants: 9 alternatively spliced, and one un-spliced version. The longest experimentally confirmed mRNA is 7240 bp long and produces a protein 1275 amino acids long.[3] The protein is predicted to weigh about 147.8kDal. It has orthologs in most animals including Aplysia californica, but is not found outside animals with the possible exception of Plasmodiophora brassicae.
# Protein information
The protein has a predicted weight of 147.8 kDal.[4][5] It does not contain a known nuclear localization signal but does contain a nuclear export signal.[6] The subcellular localization for the protein is predicted to be the nucleus and the cytoplasm.[7] This suggests that the protein might shuttle back and forth across the nuclear membrane.
## Secondary structure
Several programs suggest that the secondary structure of the protein is mainly helices with only a few beta sheets.[8][9][10][11] Analysis of protein composition also suggests that the protein has relatively low levels of glycine.[12] This could suggest a fairly rigid structure relative to other proteins.
The tertiary structure is harder to predict due to the size of the protein, partially due to its size. The 3-D structure shown shows a prediction made by I-TASSER. This is a possible strture with a C-score of -1.06 on a scale from -5 to 1 (in which the higher the number the greater the confidence).[13][14][15] This predicted structure indicates there are two main parts, and it is possible they interact depending on the state of the protein (e.g. whether or not it's phosphorylated).
# Expression
The mRNA for C5orf36 is expressed at relatively low rates in comparison to other mRNAs.[16] The protein however is expressed at relatively high rates, especially in parts of the brain as well as adrenal glands and the thyroid.[17] This would suggest that the protein is not readily degraded and remains in the cell for long periods of time, such that continuous transcription of the DNA into mRNA is unnecessary. In an expression profile done of the peripheral blood of patients with B-lymphocytic leukemia C5orf36 has slightly higher levels in patients with chronic B-lymphocytic leukemia as compared to the healthy patients.[18] Another expression profile shows that C5orf36 is expressed at lower levels in patients with Type II Diabetes compared with healthy patients.[19] No current finding suggest that there is alternative expression of different isoforms in different tissues.
# Regulation
Analysis of the promoter offers some insight into the expression of C5orf36.[20] One possible regulator found is the NeuroD1 transcription factor. This factor is an important regulator for the insulin gene, and a mutation in this gene can lead to Type II diabetes.[21] This could explain why C5orf36 is expressed at lower levels in patients with Type II diabetes. Another possible transcription factor is the Myeloid zinc finger 1 factor, which is tied to myeloid leukemia, because it delays apoptosis of cells in the presence of retinoic acid.[22] There are also several places where Vertebrate SMAD family transcription factors can bind. These transcription factors are thought to be responsible for nucleocytoplasmic dynamics.[23] This means that these SMAD transcription factors could effect C5orf36, because subcellular localization suggests it shuttles across the nuclear envelope.
# Function
There are two proteins found to interact with C5orf36. One is One is Interleukin enhancer-binding factor 3.[24] ILF3 is a factor that complexes with other proteins and regulates gene expression and stabilizes mRNAs.[25] The other is the Amyloid-beta precursor protein.[26] This protein is an integral membrane protein found most commonly in the synapses of neurons. Neither of these proteins is well enough understood to indicate for certain the role of C5orf36 in human cells. They however suggest that C5orf36 could serve a variety of roles in different parts of the cell.
# Orthology
C5orf36 orthologs can be found in virtually all animals, but cannot be found in plants, bacteria, or protozoa. It is mostly highly conserved in vertebrates especially mammals, but genes that contain region similar to DUF4495 region can be found in California sea hare, generally one of the most simple animal. The size especially in mammals is well conserved sticking very close to between 1250 and 1300 amino acids long. This suggests that the protein wraps around on itself forming important structures for its function.
There were no paralogs found of the gene C5orf36 in humans or in any other species. | https://www.wikidoc.org/index.php/C5orf36 | |
7afdda2b6e8b29e9abb59c267cfd7beb360743a6 | wikidoc | C6orf35 | C6orf35
UPF0463 transmembrane protein C6orf35 is a protein that in humans is encoded by the C6orf35 (chromosome 6 open reading frame 35) gene.
This protein contains a DUF1358 domain (Domain of Unknown Function 1358).
# Domain
The C6orf35 protein has a conserved domain of unknown function pfam 07096, DUF 1358., which covers the first 121 aa of the protein. This domain is conserved in eukaryotes.
# Associated Proteins
Several predicted interacting proteins and functional sites on the protein have been identified. One of the predicted interacting protein is MAP2K1IP1, which is a scaffold protein. This protein is known to be involved in the MAP Kinase pathway. The MAP Kinase pathway is associated with the Alzheimer's pathway through a protein called Tau or MAPT. Excessive phosphorylation of this protein leads to aggregation of neurons which can cause Alzheimer's disease. | C6orf35
UPF0463 transmembrane protein C6orf35 is a protein that in humans is encoded by the C6orf35 (chromosome 6 open reading frame 35) gene.[1]
This protein contains a DUF1358 domain (Domain of Unknown Function 1358).[2]
# Domain
The C6orf35 protein has a conserved domain of unknown function pfam 07096, DUF 1358., which covers the first 121 aa of the protein. This domain is conserved in eukaryotes.
# Associated Proteins
Several predicted interacting proteins and functional sites on the protein have been identified. One of the predicted interacting protein is MAP2K1IP1, which is a scaffold protein.[3] This protein is known to be involved in the MAP Kinase pathway. The MAP Kinase pathway is associated with the Alzheimer's pathway through a protein called Tau or MAPT. Excessive phosphorylation of this protein leads to aggregation of neurons which can cause Alzheimer's disease. | https://www.wikidoc.org/index.php/C6orf35 | |
90f6df0fc3477573648a412a15918f14e0249d75 | wikidoc | C6orf58 | C6orf58
C6orf58 is a humangene located at locus 6q22.33 of chromosome 6 and encodes for UPF0762, a protein which is subsequently secreted after cleavage of a signal peptide. DUF781, which is the singular identifiable domain in UPF0762, is tied to liver development in an orthologous protein in zebrafish. The function of the human UPF0762 is not yet well characterized.
# Gene and mRNA
## Expression
While there are 3 splice variants of C6orf58, only one encodes a good protein. In humans, C6orf58 expressed sequence tags were primarily detected in the larynx and trachea. Transcripts were only detected during the adult stage of development. Experimental microarray data, however, reveals additional regions of C6orf58 expression, namely in the salivary gland, thyroid, and small intestine. Arsenic may also regulate expression as it increases methylation of the C6orf58 promoter.
## Gene Neighborhood
Genes within 500 Kilobases of C6orf58 include RSPO3, C6orf174, KIAA0408, RPL17P23, ECHDC1, RPL5P18, YWHAZP4, LOC100420743, LOC100421513, MRPS17P5, and THEMIS.
## Homology
A selected set of homologous sequences are listed below, with sequence identity being calculated in comparison to the human reference sequence.
# Protein
## Properties
Mass spectrometry has shown that the observed molecular weight of UPF0762 is 32kDa. It remains unclear why the observed molecular weight is less than predicted, even after accounting for cleavage of the signal peptide. Attachment of a sugar at the site of N-linked glycosylation would also increase the molecular weight.
## Homology
UPF0762 shows high homology in primates and orthologous proteins can be traced back as far as trichoplax adhaerens. The list of proteins below is not a comprehensive listing of UPF0762 orthologs. Sequence identity and similarity were determined using BLAST with the reference human sequence as the query.
## Conserved domains
DUF781 is the singular domain of the protein and spans 318 of the protein's 330 amino acids. DUF781 has been linked to liver development in zebrafish.
## Post-translational modifications
Observed post-translational modifications include N-linked glycosylation at amino acid 69. A signal peptide, which is predicted to direct the protein to the endoplasmic reticulum for secretion, is cleaved from the first 20 amino acids of the peptide sequence. The missense mutation S18F detected in hepatocellular carcinoma significantly reduces the predicted cleavage score of the signal peptide.
## Interactions
Human C6orf58 has been reported to interact with the enzyme ribonucleotide reductase as encoded by the vaccinia virus through a yeast two-hybrid screen.
# Pathology
Statistical analysis has shown C6orf58 to be associated with pancreatic cancer survival time. In addition, a missense mutation at amino acid 18 has been observed in liver cancer cells where serine becomes phenylalanine. Analysis of the mutated protein sequence for a signal peptide shows cleavability at the regular amino acid 20 is lost. DUF781's association with liver development and the missense mutation's association with liver cancer is a correlation that remains to be investigated. | C6orf58
C6orf58 is a humangene located at locus 6q22.33 of chromosome 6 and encodes for UPF0762, a protein which is subsequently secreted after cleavage of a signal peptide.[1] DUF781, which is the singular identifiable domain in UPF0762, is tied to liver development in an orthologous protein in zebrafish.[2] The function of the human UPF0762 is not yet well characterized.[3]
# Gene and mRNA
## Expression
While there are 3 splice variants of C6orf58, only one encodes a good protein.[3] In humans, C6orf58 expressed sequence tags were primarily detected in the larynx and trachea.[4] Transcripts were only detected during the adult stage of development.[4] Experimental microarray data, however, reveals additional regions of C6orf58 expression, namely in the salivary gland, thyroid, and small intestine.[5] Arsenic may also regulate expression as it increases methylation of the C6orf58 promoter.[6]
## Gene Neighborhood
Genes within 500 Kilobases of C6orf58 include RSPO3, C6orf174, KIAA0408, RPL17P23, ECHDC1, RPL5P18, YWHAZP4, LOC100420743, LOC100421513, MRPS17P5, and THEMIS.
## Homology
A selected set of homologous sequences are listed below, with sequence identity being calculated in comparison to the human reference sequence.
# Protein
## Properties
Mass spectrometry has shown that the observed molecular weight of UPF0762 is 32kDa.[8] It remains unclear why the observed molecular weight is less than predicted, even after accounting for cleavage of the signal peptide. Attachment of a sugar at the site of N-linked glycosylation would also increase the molecular weight.
## Homology
UPF0762 shows high homology in primates and orthologous proteins can be traced back as far as trichoplax adhaerens. The list of proteins below is not a comprehensive listing of UPF0762 orthologs. Sequence identity and similarity were determined using BLAST[9] with the reference human sequence as the query.
## Conserved domains
DUF781 is the singular domain of the protein and spans 318 of the protein's 330 amino acids. DUF781 has been linked to liver development in zebrafish.[2]
## Post-translational modifications
Observed post-translational modifications include N-linked glycosylation at amino acid 69.[10] A signal peptide, which is predicted to direct the protein to the endoplasmic reticulum for secretion,[11] is cleaved from the first 20 amino acids of the peptide sequence.[1] The missense mutation S18F detected in hepatocellular carcinoma[12] significantly reduces the predicted cleavage score of the signal peptide.[13]
## Interactions
Human C6orf58 has been reported to interact with the enzyme ribonucleotide reductase as encoded by the vaccinia virus through a yeast two-hybrid screen.[14]
# Pathology
Statistical analysis has shown C6orf58 to be associated with pancreatic cancer survival time.[15] In addition, a missense mutation at amino acid 18 has been observed in liver cancer cells where serine becomes phenylalanine.[12] Analysis of the mutated protein sequence for a signal peptide shows cleavability at the regular amino acid 20 is lost.[13] DUF781's association with liver development and the missense mutation's association with liver cancer is a correlation that remains to be investigated. | https://www.wikidoc.org/index.php/C6orf58 | |
82e8aa881ad1eefd53b6c77b26a9e7ab9020e29d | wikidoc | C6orf62 | C6orf62
Chromosome 6 open reading frame 62 (C6orf62), also known as X-trans-activated protein 12 (XTP12), is a gene that encodes a protein of the same name. The encoded protein is predicted to have a subcellular location within the cytosol.
# Gene and Transcript
In the DNA, C6orf62 is 12,529 base pairs long and is located at 6q22.3. It is located on chromosome 6 on position 22.3 (6q22.3). The mature mRNA sequence is 2498 base-pairs long with 5 exons and 4 intronic regions that translates a protein that is 229 amino acids long and two predicted isoforms of 160 amino acids and 200 amino acids.
# Protein
The main transcript is 229 amino acids long and is encoded from 5 exonic regions. There exists two transcript variants that are 200 amino acids and 160 amino acids long. There is a domain of unknown function (DUF4566) present in all three variants and spans positions 1-226 on the main transcript. The molecular weight of C6orf62 is 27.1 kDa and its isoelectric point is at a pH of 9.24. It is located subcellularly localized throughout the cytosol.
## Protein Interactions
# Expression
C6orf62 is broadly expressed within the human body, however, its protein abundance is not high. It is more heavily expressed in the gallbladder and testis, but it is not predicted to be expressed in the smooth muscle, lymph nodes, the spleen, ovaries, adipose tissue, and soft tissue.
# Homology
C6orf62 is highly conserved among vertebrates and has orthologs found in invertebrates.
## Orthologs in Select Mammals
## Orthologs in Select Ray-Finned Fish
## Orthologs in Select Amphibians
## Orthologs in Select Reptiles
## Orthologs in Select Birds
Orthologs in Select Invertebrates | C6orf62
Chromosome 6 open reading frame 62 (C6orf62), also known as X-trans-activated protein 12 (XTP12),[1] is a gene that encodes a protein of the same name. The encoded protein is predicted to have a subcellular location within the cytosol.[2]
# Gene and Transcript
In the DNA, C6orf62 is 12,529 base pairs long and is located at 6q22.3.[3] It is located on chromosome 6 on position 22.3 (6q22.3). The mature mRNA sequence is 2498 base-pairs long with 5 exons and 4 intronic regions that translates a protein that is 229 amino acids long and two predicted isoforms of 160 amino acids and 200 amino acids.[4][5]
# Protein
The main transcript is 229 amino acids long and is encoded from 5 exonic regions. There exists two transcript variants that are 200 amino acids and 160 amino acids long. There is a domain of unknown function (DUF4566) present in all three variants and spans positions 1-226 on the main transcript.[6] The molecular weight of C6orf62 is 27.1 kDa and its isoelectric point is at a pH of 9.24.[7] It is located subcellularly localized throughout the cytosol.[2]
## Protein Interactions
# Expression
C6orf62 is broadly expressed within the human body, however, its protein abundance is not high.[10] It is more heavily expressed in the gallbladder and testis, but it is not predicted to be expressed in the smooth muscle, lymph nodes, the spleen, ovaries, adipose tissue, and soft tissue.
# Homology
C6orf62 is highly conserved among vertebrates and has orthologs found in invertebrates.
## Orthologs in Select Mammals[11]
## Orthologs in Select Ray-Finned Fish[11]
## Orthologs in Select Amphibians[11]
## Orthologs in Select Reptiles[11]
## Orthologs in Select Birds[11]
Orthologs in Select Invertebrates[11] | https://www.wikidoc.org/index.php/C6orf62 | |
91fc2a50a88ca65d126231fd5f780574b531b5e8 | wikidoc | C7orf25 | C7orf25
C7orf25 protein UPF0415 (UPF0415) is a protein encoded on chromosome 7, in open reading frame 25 (C7orf25) and are located at domain of unknown function 1308. C7orf25 is located at the minus strand and encodes 12 proteins, one of them being UPF0415. This protein is believed to be active in the proteosome pathway. C7orf25 protein UPF0415 is not a transmembrane protein and has no signal peptide. UPF0415 has two isoforms, Q9BPX7-1 and Q9BPX7-2. Both consists of two exons that are both highly conserved among vertebrates.
# Background information
# Gene neighborhood
C7orf25 is an open reading frame that encodes 12 proteins. Most of these are of unknown function. One of these proteins is UPF0415 and another is PSMA2 which is also functional in the proteosome pathway. Other genes located near C7orf25 protein UPF0415 are TCP1P1, HECW1, MIR3943 and MRPL32.
# Predicted mRNA features
## Promoter
The promoter for the C7orf25 protein UPF0415 gene spans 600 base pairs from 42,951,804 to 42,952,404 with a predicted transcriptional start site that encodes a sequence of 1844 base pairs. The sequence spans from 42,908,726 to 42,912,090. The promoter region and beginning of the C7orf25 gene (20,008,263 to 20,009,250) is not conserved past primates. This region was used to determine transcription factor interactions.
### Transcription factors
Some of the main transcription factors that bind to the promoter are listed below.
# Function and expression
C7orf25 protein UPF0415 is believed to be active in ATP dependent protein breakdown in the proteosome pathway. It is expressed ubiquitously in humans.
# Homology
UPF0415 protein C7orf25 has one paralog which is FLJ18411. UPF0415 is also highly conserved in vertebrates. The following table shows a small selection of orthologs found using BLAST and BLAT and their identity to C7orf25 protein UPF0415.
# Predicted protein features
## Post Translational Modifications
UPF0415 protein C7orf25 is not a transmembrane protein as it has no transmembrane domains. C7orf25 protein UPF0415 has multiple phosphorylation which are believed to be responsible in protein activation.
Multiple stem loops have been predicted in both 3` and 5`UTR and these are believed to be functional in gene transcription.
3`UTR and 5`UTR stem loops
# = Interactions
Other proteins that are known to interact with UPF0415 protein C7orf25 are FRA10AC1, FLJ23825 and TUBB (tubulin, beta class I) and only TUBB is associated with proteosome activity.
## Conceptual presentation
All post transnational modifications, genetic or proteomic factors that are relevant for UPF0415 protein C7orf25 transcription and regulation, mentioned above, are annotated in the conceptual translation.
# C7orf25
C7orf25 encodes 12 different transcripts. Two of these transcripts are (PSMA2 and UPF0415). No specific phenotypes or polymorphisms are yet to be related to mutations in C7orf25. This suggests that this reading frame is important for survival in vertebrates. The picture below shows all predicted transcripts encoded in C7orf25. | C7orf25
C7orf25 protein UPF0415 (UPF0415) is a protein encoded on chromosome 7, in open reading frame 25 (C7orf25) and are located at domain of unknown function 1308. C7orf25 is located at the minus strand and encodes 12 proteins, one of them being UPF0415. This protein is believed to be active in the proteosome pathway. C7orf25 protein UPF0415 is not a transmembrane protein and has no signal peptide. UPF0415 has two isoforms, Q9BPX7-1 and Q9BPX7-2. Both consists of two exons that are both highly conserved among vertebrates.
# Background information
# Gene neighborhood
C7orf25 is an open reading frame that encodes 12 proteins. Most of these are of unknown function. One of these proteins is UPF0415 and another is PSMA2 which is also functional in the proteosome pathway.[2] Other genes located near C7orf25 protein UPF0415 are TCP1P1, HECW1, MIR3943 and MRPL32.
# Predicted mRNA features
## Promoter
The promoter for the C7orf25 protein UPF0415 gene spans 600 base pairs from 42,951,804 to 42,952,404 with a predicted transcriptional start site that encodes a sequence of 1844 base pairs. The sequence spans from 42,908,726 to 42,912,090.[3] The promoter region and beginning of the C7orf25 gene (20,008,263 to 20,009,250) is not conserved past primates. This region was used to determine transcription factor interactions.
### Transcription factors
Some of the main transcription factors that bind to the promoter are listed below.[4]
# Function and expression
C7orf25 protein UPF0415 is believed to be active in ATP dependent protein breakdown in the proteosome pathway. It is expressed ubiquitously in humans.[5]
# Homology
UPF0415 protein C7orf25 has one paralog which is FLJ18411.[6] UPF0415 is also highly conserved in vertebrates. The following table shows a small selection of orthologs found using BLAST and BLAT and their identity to C7orf25 protein UPF0415.
# Predicted protein features
## Post Translational Modifications
UPF0415 protein C7orf25 is not a transmembrane protein as it has no transmembrane domains. C7orf25 protein UPF0415 has multiple phosphorylation which are believed to be responsible in protein activation.[7]
Multiple stem loops have been predicted in both 3` and 5`UTR and these are believed to be functional in gene transcription.[8]
3`UTR and 5`UTR stem loops
# = Interactions
=
Other proteins that are known to interact with UPF0415 protein C7orf25 are FRA10AC1, FLJ23825 and TUBB (tubulin, beta class I) and only TUBB is associated with proteosome activity.
## Conceptual presentation
All post transnational modifications, genetic or proteomic factors that are relevant for UPF0415 protein C7orf25 transcription and regulation, mentioned above, are annotated in the conceptual translation.
# C7orf25
C7orf25 encodes 12 different transcripts. Two of these transcripts are (PSMA2 and UPF0415). No specific phenotypes or polymorphisms are yet to be related to mutations in C7orf25. This suggests that this reading frame is important for survival in vertebrates. The picture below shows all predicted transcripts encoded in C7orf25.[9] | https://www.wikidoc.org/index.php/C7orf25 | |
a05378bd21553c098b65d759c2807164c91b402b | wikidoc | C7orf30 | C7orf30
C7ORF30 (chromosome 7 open reading frame 30) is a gene on chromosome 7 in humans that encodes the protein LOC_115416. This protein localizes to mitochondria and is probably involved in mitochondrial translation or the biogenesis of the large subunit of the mitochondrial ribosome.
# Protein
LOC_115416 is a member of the DUF143 family (= domain of unknown function 143, Pfam PF02410) which is highly conserved in both prokaryotes and eukaryotes but not archaea. Examples of mammalian conservation are given below using the ALIGN tool from the San Diego Supercomputer Center Biology Workbench. Percentages indicate the identity shared by the human protein and the respective mammalian protein. Accession numbers are from the NCBI database.
There are no known or predicted paralogs in Homo sapiens. That is, C7Orf30 is a single-copy gene.
The domain is from position 93 to 194 on the human protein and comprises 43.2% of the sequence. This conserved domain is also present in the plant gene iojap, a pattern-striping gene in maize. However, since its function has been solved at least in bacteria, it is no longer a "domain of unknown function".
## Protein function
While the function of the protein in mitochondria is not conclusive its bacterial homolog has been shown to silence prokaryotic translation by blocking the two ribosomal subunits from joining, hence it was called RsfS (= ribosomal silencing factor in starvation or stationary phase, a synonym of RsfA).
Protein-protein interactions. RsfS has been shown via a yeast two-hybrid screen to interact with ribosomal protein L14 in four bacterial species as well as in mitochondria. C7Orf30 was shown to interact with CHMP protein which is part of the ESCRT-III complex (Endosomal Sorting Complex Required for Transport). DUF143 has also been shown to interact with UFD1, tRNA synthetases class II, and Cytidylyltransferase in various architectures.
## Properties
Bioinformatics predicted the following properties for LOC_115416:
- Molecular Weight: 26.2 KDal
- Isoelectric Point: 5.155
# Gene
C7ORF30 is located on chromosome 7 in humans and runs from 23,305,465 to 23,315,705. There are four predicted exons in the human gene with conservation occurring across most mammalian species. There is no conclusive data regarding whether the gene is ubiquitously expressed in human tissues, but expressed sequence tag databases show that it is expressed in many tissues.
## Neighboring Genes
C7ORF30 is neighbored by GPNMB upstream and IGF2BP3 downstream, however the latter gene is transcribed on the opposite strand running from the 3' to the 5' end. There is some slight overlap of the untranslated regions of C7ORF30 and IGF2BP3 whereas the distance between C7ORF30 and GPNMB is 24,211 base pairs. | C7orf30
C7ORF30 (chromosome 7 open reading frame 30) is a gene on chromosome 7 in humans that encodes the protein LOC_115416.[1] This protein localizes to mitochondria and is probably involved in mitochondrial translation or the biogenesis of the large subunit of the mitochondrial ribosome.
# Protein
LOC_115416 is a member of the DUF143[2] family (= domain of unknown function 143, Pfam PF02410) which is highly conserved in both prokaryotes and eukaryotes but not archaea.[3] Examples of mammalian conservation are given below using the ALIGN tool from the San Diego Supercomputer Center Biology Workbench.[4] Percentages indicate the identity shared by the human protein and the respective mammalian protein. Accession numbers are from the NCBI database.
There are no known or predicted paralogs in Homo sapiens. That is, C7Orf30 is a single-copy gene.
The domain is from position 93 to 194 on the human protein and comprises 43.2% of the sequence. This conserved domain is also present in the plant gene iojap, a pattern-striping gene in maize.[5][6] However, since its function has been solved at least in bacteria, it is no longer a "domain of unknown function".
## Protein function
While the function of the protein in mitochondria is not conclusive[7][8] its bacterial homolog has been shown to silence prokaryotic translation by blocking the two ribosomal subunits from joining, hence it was called RsfS (= ribosomal silencing factor in starvation or stationary phase, a synonym of RsfA[9]).
Protein-protein interactions. RsfS has been shown via a yeast two-hybrid screen to interact with ribosomal protein L14 in four bacterial species as well as in mitochondria.[9] C7Orf30 was shown to interact with CHMP protein[10] which is part of the ESCRT-III complex (Endosomal Sorting Complex Required for Transport). DUF143 has also been shown to interact with UFD1, tRNA synthetases class II, and Cytidylyltransferase in various architectures.[11]
## Properties
Bioinformatics predicted the following properties for LOC_115416:
- Molecular Weight: 26.2 KDal
- Isoelectric Point: 5.155
# Gene
C7ORF30 is located on chromosome 7 in humans and runs from 23,305,465 to 23,315,705.[12] There are four predicted exons in the human gene with conservation occurring across most mammalian species. There is no conclusive data regarding whether the gene is ubiquitously expressed in human tissues, but expressed sequence tag databases show that it is expressed in many tissues.[13]
## Neighboring Genes
C7ORF30 is neighbored by GPNMB upstream and IGF2BP3 downstream, however the latter gene is transcribed on the opposite strand running from the 3' to the 5' end. There is some slight overlap of the untranslated regions of C7ORF30 and IGF2BP3 whereas the distance between C7ORF30 and GPNMB is 24,211 base pairs. | https://www.wikidoc.org/index.php/C7orf30 | |
6472df719c346c0640f5d3c462d0a582754b5e9d | wikidoc | C7orf31 | C7orf31
Chromosome Seven Open Reading Frame 31 (C7orf31) is a protein that in humans is encoded by the C7orf31 gene on chromosome seven.
# Gene/Locus
In humans, the C7orf31 gene is located at the locus 7p15.3 and stretches between position 25174316 and 25219817 (span 45502 bp). It codes for at least 4 unique human isoforms: the primary isoform (590 aa; also denoted X1, X2, and CRA_c), isoform X4 (346 aa), isoform CRA_a (580 aa), and isoform CRA_b (380 aa).
# Transcript
In humans, C7orf31 codes for an mRNA strand that is 3609 base pairs long. The human mRNA is composed of a 5' untranslated region that is 561 bases and a 3' untranslated region that is 1275 bases long.
# Protein
The primary protein encoded by C7orf31 in humans is 590 amino acids long with molecular weight 38334 Da. The protein is part of a functionally uncharacterized family of proteins (pfam15093) with a domain of unknown function (DUF4555).
# Protein Orthology
The C7orf31 protein is well-conserved in mammals and birds, but is less conserved in more distant organisms.
C7orf31 does not have any paralogs in humans.
# Expression
In humans, C7orf31 is predicted to be localized in the cytosol, nucleus, mitochondrion, and peroxisome, and it is expressed in almost all tissues. It is highly expressed especially in the testes.
# Interaction
Two-hybrid studies have found interactions between the proteins encoded by A8K5H9 and C7orf31,
A study in 2014 found C7orf31 to be a candidate as a centrosome-associated protein, using mass spectrometry on mammalian sperm cells’ centrioles. The protein appears in the study alongside seven other centrosome-associated protein candidates. Along with 2241 other proteins, C7orf31 also exhibited significant binding in a microarray experiment to β-amyloids, a group of proteins associated with Alzheimer's disease. Finally, in a protein-protein interaction network study, C7orf31 was found to associate with KLHL40, whose exact function is also not known. | C7orf31
Chromosome Seven Open Reading Frame 31 (C7orf31) is a protein that in humans is encoded by the C7orf31 gene on chromosome seven.[1]
# Gene/Locus
In humans, the C7orf31 gene is located at the locus 7p15.3 [1] and stretches between position 25174316 and 25219817 (span 45502 bp).[2] It codes for at least 4 unique human isoforms: the primary isoform (590 aa; also denoted X1, X2, and CRA_c),[3][4][5] isoform X4 (346 aa),[6] isoform CRA_a (580 aa),[7] and isoform CRA_b (380 aa).[8]
# Transcript
In humans, C7orf31 codes for an mRNA strand that is 3609 base pairs long. The human mRNA is composed of a 5' untranslated region that is 561 bases and a 3' untranslated region that is 1275 bases long.[9]
# Protein
The primary protein encoded by C7orf31 in humans is 590 amino acids long with molecular weight 38334 Da.[1] The protein is part of a functionally uncharacterized family of proteins (pfam15093) with a domain of unknown function (DUF4555).[10]
# Protein Orthology
The C7orf31 protein is well-conserved in mammals and birds, but is less conserved in more distant organisms.[11]
C7orf31 does not have any paralogs in humans.
# Expression
In humans, C7orf31 is predicted to be localized in the cytosol, nucleus, mitochondrion, and peroxisome, and it is expressed in almost all tissues.[12] It is highly expressed especially in the testes.[13]
# Interaction
Two-hybrid studies have found interactions between the proteins encoded by A8K5H9 and C7orf31,[14]
A study in 2014 found C7orf31 to be a candidate as a centrosome-associated protein, using mass spectrometry on mammalian sperm cells’ centrioles. The protein appears in the study alongside seven other centrosome-associated protein candidates.[16] Along with 2241 other proteins, C7orf31 also exhibited significant binding in a microarray experiment to β-amyloids, a group of proteins associated with Alzheimer's disease.[17] Finally, in a protein-protein interaction network study,[18] C7orf31 was found to associate with KLHL40, whose exact function is also not known.[19] | https://www.wikidoc.org/index.php/C7orf31 | |
65fa82d0143c37e07fce6c25d3202d04e7c2945d | wikidoc | C7orf43 | C7orf43
C7orf43 (Chromosome 7 Open reading frame 43) is a protein that in human is encoded by the gene C7orf43. C7orf43 has no other human alias, but in mice can be found as BC037034.
# Gene Locus
In humans, C7orf43 is located in the long arm of human chromosome 7 (7q22.1), and is on the negative (antisense) strand. Genes located around C7orf43 include GAL3ST4, LAMTOR4, GPC2. In humans, C7orf43 has 9 detected common single-nucleotide polymorphisms (SNPs), all of which are located in non-coding regions and thus do not affect amino acid sequence.
# mRNA
## Splice variants
C7orf43 encodes 2 isoforms, the longest being C7orf43 isoform 1, which is 2585 base pairs long and has with 11 exons and 10 introns. C7orf43 isoform 1 encodes a protein that is 580 amino acids long and only has one polyadenylation site. C7orf43 isoform 2 is 2085 base pairs long and encodes a protein of 311 amino acids. Two additional isoforms has been reported on several occasions, encoding for proteins with 199 and 206 amino acids.
## Tissue expression
C7orf43 has a widespread moderate expression with tissue to tissue variability in humans and across mammalian species. The mouse C7orf43 ortholog has been shown to be ubiquitously expressed in the brain, as well as in the mouse embryonic central nervous system.
## Regulations
C7orf43 has one promoter region upstream of its transcription site, as predicted by Genomatix. This promoter is 657 base pairs long and is located at position 99756182 to 99756838 in the negative strand of chromosome 7. There are several transcription factor binding sites located in this promoter, including binding sites for zinc fingers and Kruppel-like transcription factors. The top 20 transcription binding sites as predicted by the ElDorado from Genomatix is listed in the following table.
# Protein
## Composition and Domains
The human protein C7orf43 has an isoelectric point of 8.94. C7orf43 also has a glycine-rich region spanning amino acids 54 through 134. Analysis using the SAPS tool from the SDSC Biology Workbench showed this glycine-rich region to not be conserved in terms of specific glycine residue positions, but is well conserved in overall glycine content in mammals and reptiles, although not in bony fishes. C7orf43 is mostly uncharged, and this neutral charge distribution is conserved in mammals and reptiles, but bony fishes have at least one negative charge cluster
C7orf43 is predicted to have no signal peptide in its first 70 amino acid residues. However, it is predicted to have a vacuolar targeting motif starting at residue 258 in the human protein. This vacuolar targeting motif is shown to be conserved throughout mammals, reptiles, birds, amphibians, and bony fishes.
## Evolutionary history
The C7orf43 protein has no paralogs in humans. However, C7orf43 orthologs can be found to be highly conserved in mammals, reptiles, and several species of bony fishes. C7orf43 is also conserved in birds, although several bird species lack parts of the N-terminus. No C7orf43 orthologs can be found outside the animal kingdom. The following table lists representative C7orf43 orthologs across multiple animal classes.
### Strict orthologs
### Distant orthologs
## Post-translational modifications
C7orf43 has three phosphorylated sites, Ser 517, Thr 541 and, Ser 546. All three sites are relatively well-conserved throughout mammals, reptiles, birds, amphibians, and bony fishes. The protein has no predicted N-myristoylation, as it has no N-terminal glycine. However, C7orf43 is predicted to have one N-acetylation on a serine residue at the N-terminus.
## Secondary structure
The secondary structure of C7orf43 is yet to be determined. However, C7orf43 is predicted to have no transmembrane domain and to eventually be secreted from the cell. An analysis using the PELE tool from SDSC Biology Workbench predicted mostly beta sheets and random coils that are conserved throughout the strict orthologs. Similarly conserved alpha helix motifs have been predicted, one near the N-terminus and one near the C-terminus.
# Clinical significance
While no studies have focused on the characterization of C7orf43, several large-scale screenings have revealed information related to C7orf43 function. A study using FLAG affinity purification mass spectrometry (AP-MS) to profile protein interactions in the Hippo signaling pathway identified C7orf43 as one of the interacting proteins. C7orf43 was found to interact with angiomotin-like protein 2 (AMOTL2), also known as Leman Coiled-Coil Protein (LCCP), a regulator of Hippo signaling. AMOTL2 is also known to be an inhibitor of Wnt signaling, a pathway with known associations to cancer development, and to be a factor for angiogenesis, a process essential to tumour maintenance and metastasis.
Several studies have linked C7orf43 to carcinomic events. Other studies have also linked C7orf43 to carcinomic events. A large-scale yeast two-hybrid experiment identified C7orf43 to be interacting with transmembrane protein 50A (TMEM50A), also known as cervical cancer gene 9 or small membrane protein 1 (SMP1). While the exact function of TMEM50A is unknown, it has been associated with cervical cancer.
C7orf43 has also been identified as a target gene of the transcription factor AP-2 gamma (TFAP2C). TFAP2C has been shown to be involved in the development, differentiation, and oncogenesis of mammary tissues. Specifically, TFAP2C has a role in breast carcinoma through its regulatory effect to ESR1 and ERBB2, both of which are receptors whose aberrations have been associated with breast carcinomas. TFAP2C has also been shown to have an oncogenic role by promotion of cell proliferation and tumour growth in neuroblastoma.
Through its location in the q arm of chromosome 7, C7orf43 has been linked to various diseases. Several diseases have been described as having deletions in the q arm of chromosome 7, among them are myeloid disorders, including acute myelogenous leukemia and myelodysplasia. | C7orf43
C7orf43 (Chromosome 7 Open reading frame 43) is a protein that in human is encoded by the gene C7orf43.[1] C7orf43 has no other human alias, but in mice can be found as BC037034.[2]
# Gene Locus
In humans, C7orf43 is located in the long arm of human chromosome 7 (7q22.1), and is on the negative (antisense) strand.[1] Genes located around C7orf43 include GAL3ST4, LAMTOR4, GPC2.[1] In humans, C7orf43 has 9 detected common single-nucleotide polymorphisms (SNPs), all of which are located in non-coding regions and thus do not affect amino acid sequence.[3]
# mRNA
## Splice variants
C7orf43 encodes 2 isoforms, the longest being C7orf43 isoform 1, which is 2585 base pairs long and has with 11 exons and 10 introns.[1] C7orf43 isoform 1 encodes a protein that is 580 amino acids long and only has one polyadenylation site.[1] C7orf43 isoform 2 is 2085 base pairs long and encodes a protein of 311 amino acids. Two additional isoforms has been reported on several occasions, encoding for proteins with 199 and 206 amino acids.[4]
## Tissue expression
C7orf43 has a widespread moderate expression with tissue to tissue variability in humans and across mammalian species.[5][6] The mouse C7orf43 ortholog has been shown to be ubiquitously expressed in the brain,[7] as well as in the mouse embryonic central nervous system.[8]
## Regulations
C7orf43 has one promoter region upstream of its transcription site, as predicted by Genomatix. This promoter is 657 base pairs long and is located at position 99756182 to 99756838 in the negative strand of chromosome 7.[9] There are several transcription factor binding sites located in this promoter, including binding sites for zinc fingers and Kruppel-like transcription factors.[10] The top 20 transcription binding sites as predicted by the ElDorado from Genomatix is listed in the following table.
# Protein
## Composition and Domains
The human protein C7orf43 has an isoelectric point of 8.94. C7orf43 also has a glycine-rich region spanning amino acids 54 through 134.[11] Analysis using the SAPS tool from the SDSC Biology Workbench showed this glycine-rich region to not be conserved in terms of specific glycine residue positions, but is well conserved in overall glycine content in mammals and reptiles, although not in bony fishes.[12][13] C7orf43 is mostly uncharged, and this neutral charge distribution is conserved in mammals and reptiles, but bony fishes have at least one negative charge cluster [12][13]
C7orf43 is predicted to have no signal peptide in its first 70 amino acid residues. However, it is predicted to have a vacuolar targeting motif starting at residue 258 in the human protein.[14] This vacuolar targeting motif is shown to be conserved throughout mammals, reptiles, birds, amphibians, and bony fishes.
## Evolutionary history
The C7orf43 protein has no paralogs in humans. However, C7orf43 orthologs can be found to be highly conserved in mammals, reptiles, and several species of bony fishes. C7orf43 is also conserved in birds, although several bird species lack parts of the N-terminus.[15] No C7orf43 orthologs can be found outside the animal kingdom.[15] The following table lists representative C7orf43 orthologs across multiple animal classes.
### Strict orthologs
### Distant orthologs
## Post-translational modifications
C7orf43 has three phosphorylated sites, Ser 517, Thr 541 and, Ser 546.[11] All three sites are relatively well-conserved throughout mammals, reptiles, birds, amphibians, and bony fishes. The protein has no predicted N-myristoylation, as it has no N-terminal glycine.[16] However, C7orf43 is predicted to have one N-acetylation on a serine residue at the N-terminus.[17]
## Secondary structure
The secondary structure of C7orf43 is yet to be determined. However, C7orf43 is predicted to have no transmembrane domain and to eventually be secreted from the cell.[18][19] An analysis using the PELE tool from SDSC Biology Workbench predicted mostly beta sheets and random coils that are conserved throughout the strict orthologs.[13] Similarly conserved alpha helix motifs have been predicted, one near the N-terminus and one near the C-terminus.
# Clinical significance
While no studies have focused on the characterization of C7orf43, several large-scale screenings have revealed information related to C7orf43 function. A study using FLAG affinity purification mass spectrometry (AP-MS) to profile protein interactions in the Hippo signaling pathway identified C7orf43 as one of the interacting proteins.[20] C7orf43 was found to interact with angiomotin-like protein 2 (AMOTL2), also known as Leman Coiled-Coil Protein (LCCP), a regulator of Hippo signaling.[20][21] AMOTL2 is also known to be an inhibitor of Wnt signaling, a pathway with known associations to cancer development, and to be a factor for angiogenesis, a process essential to tumour maintenance and metastasis.[21]
Several studies have linked C7orf43 to carcinomic events. Other studies have also linked C7orf43 to carcinomic events. A large-scale yeast two-hybrid experiment identified C7orf43 to be interacting with transmembrane protein 50A (TMEM50A), also known as cervical cancer gene 9 or small membrane protein 1 (SMP1).[22][23][24] While the exact function of TMEM50A is unknown, it has been associated with cervical cancer.
C7orf43 has also been identified as a target gene of the transcription factor AP-2 gamma (TFAP2C).[25] TFAP2C has been shown to be involved in the development, differentiation, and oncogenesis of mammary tissues. Specifically, TFAP2C has a role in breast carcinoma through its regulatory effect to ESR1 and ERBB2, both of which are receptors whose aberrations have been associated with breast carcinomas.[25][26] TFAP2C has also been shown to have an oncogenic role by promotion of cell proliferation and tumour growth in neuroblastoma.[27][28]
Through its location in the q arm of chromosome 7, C7orf43 has been linked to various diseases. Several diseases have been described as having deletions in the q arm of chromosome 7, among them are myeloid disorders, including acute myelogenous leukemia and myelodysplasia.[29] | https://www.wikidoc.org/index.php/C7orf43 | |
2ee501b71da7eab8826b3f11848f5c0b68cf88f7 | wikidoc | C7orf61 | C7orf61
Uncharacterized protein chromosome 7 open reading frame 61 is an asparagine-poor protein in humans encoded by the c7orf61 gene. The protein function is relatively unknown and is highly conserved in mammals.
# Gene
## Locus
C7orf61 is located on the reverse (or negative) DNA strand and is situated in chromosome 7 (7q22.1) from base pairs 100,456,615-100,464,271 - roughly 7,656 bp. It has a total of 3 exons and lacks isoforms.
## mRNA
The mRNA is approximately 1019 bp and belongs to domain of unknown function 4703 (PFAM15775).
## Protein
In humans, the protein contains a total of 206 amino acids. The protein's molecular weight is 23.71 kDa and it's isoelectric point is 10.41. DUF4703 is positioned 22-206aa of the protein. Neither the gene or its protein has another known alias, but can be found with high affinity in several primate species.
## Composition
The amino acid composition of C7orf61 consists of high frequencies in leucine, serine, and charged valine. The protein has an unusual low frequency in asparagine, making it an asparagine-deficient protein , and contains higher frequencies of salt-bridge formations between glutamic acid, aspartic acid, lysine, and arginine.
## Characteristics and structure
The consent within secondary structure prediction tools CFSSP, SSPRED, and GOR4 is that the protein's secondary structure consist mainly of α-helices (51.2%), with significant amounts of coiling (38.2%) and smaller fragments of beta strands (10.3%).
## Post-translational modifications
C7orf61 has several post-translation modification sites, most of which involve serine/threonine kinases - protein kinase C, Casein kinase II, DNA-dependent protein kinase, and Cyclin-dependent kinase 1. It is predicted to contain a Biparte nuclear localization signal (NLS_BP), a leucine-rich variant domain (LRV), and bacterial Ig-like domain (BIG-1).
## Subcellular localization
C7orf61 does not contain any trans-membrane domains or signal peptides. The protein is predicted to be localized in the Mitochondria, with little indication of extracellular activity. Expanded analysis of amino acid sequence KFFRWVRRAWQRIISWVF near the N-terminal suggests the presence of a mitochondrial targeting signal.
# Gene regulation
C7orf61 has high levels of expression in the testis and lower levels in the brain and connective tissues. Through the assessment of microarray experiments available on NCBI Geo, it's inferred that c7orf61 is under negative regulation.
# Homology
C7orf61 does not have any paralogs. Analysis via NCBI tool BLASTt found the gene to be highly conserved in mammals and could not be traced farther back than 160 MYA. The following table contains a list of orthologs found in several mammalian sub-classes - this is not a comprehensive list for the proteins orthology. | C7orf61
Uncharacterized protein chromosome 7 open reading frame 61 is an asparagine-poor protein in humans encoded by the c7orf61 gene. The protein function is relatively unknown and is highly conserved in mammals.
# Gene
## Locus
C7orf61 is located on the reverse (or negative) DNA strand and is situated in chromosome 7 (7q22.1) from base pairs 100,456,615-100,464,271 - roughly 7,656 bp. [1] It has a total of 3 exons and lacks isoforms.
## mRNA
The mRNA is approximately 1019 bp and belongs to domain of unknown function 4703 (PFAM15775).[2]
## Protein
In humans, the protein contains a total of 206 amino acids.[1] The protein's molecular weight is 23.71 kDa and it's isoelectric point is 10.41.[3] DUF4703 is positioned 22-206aa of the protein.[1] Neither the gene or its protein has another known alias, but can be found with high affinity in several primate species.[4]
## Composition
The amino acid composition of C7orf61 consists of high frequencies in leucine, serine, and charged valine.[5] The protein has an unusual low frequency in asparagine, making it an asparagine-deficient protein [5], and contains higher frequencies of salt-bridge formations between glutamic acid, aspartic acid, lysine, and arginine.[5]
## Characteristics and structure
The consent within secondary structure prediction tools CFSSP[6], SSPRED[7], and GOR4 [8] is that the protein's secondary structure consist mainly of α-helices (51.2%), with significant amounts of coiling (38.2%) and smaller fragments of beta strands (10.3%).
## Post-translational modifications
C7orf61 has several post-translation modification sites, most of which involve serine/threonine kinases - protein kinase C, Casein kinase II, DNA-dependent protein kinase, and Cyclin-dependent kinase 1. It is predicted to contain a Biparte nuclear localization signal (NLS_BP), a leucine-rich variant domain (LRV), and bacterial Ig-like domain (BIG-1).[10]
## Subcellular localization
C7orf61 does not contain any trans-membrane domains or signal peptides.[11][12] The protein is predicted to be localized in the Mitochondria, with little indication of extracellular activity. [13][14] Expanded analysis of amino acid sequence KFFRWVRRAWQRIISWVF near the N-terminal suggests the presence of a mitochondrial targeting signal. [15]
# Gene regulation
C7orf61 has high levels of expression in the testis and lower levels in the brain and connective tissues.[16] Through the assessment of microarray experiments available on NCBI Geo, it's inferred that c7orf61 is under negative regulation. [17]
# Homology
C7orf61 does not have any paralogs. Analysis via NCBI tool BLASTt[18] found the gene to be highly conserved in mammals and could not be traced farther back than 160 MYA. The following table contains a list of orthologs found in several mammalian sub-classes - this is not a comprehensive list for the proteins orthology. | https://www.wikidoc.org/index.php/C7orf61 | |
45f54576856febe251c002f034f2b76e7d7705b7 | wikidoc | C8orf48 | C8orf48
C8orf48 is a protein that in humans is encoded by the C8orf48 gene. C8orf48 is a nuclear protein specifically predicted to be located in the nuclear lamina. C8orf48 has been found to interact with proteins that are involved in the regulation of various cellular responses like gene expression, protein secretion, cell proliferation, and inflammatory responses. This protein has been linked to breast cancer and papillary thyroid carcinoma.
# Gene
C8orf48 is located on chromosome 8 (8p22) and spans from 13,566,843 to 13,568,288 on the positive strand. C8orf48 has an exon count of 1 and no introns. This protein does not have any isoforms nor exhibit any alternative splicing.
# Protein
The protein C8orf48 is 319 amino acids in length. The molecular weight of this protein is 36.9 kDa and the isoelectric point is 8.86. The C8orf48 protein is predicted to be a nuclear protein particularly located in the nuclear lamina. This protein does not possess any signal peptides or transmembrane domains. This protein has also been found to be fairly abundant in humans.
## Structure
C8orf48 protein has two predicted nuclear localization signals one spanning from 135-149 amino acids and the other from 204-221. The secondary structure of C8orf48 protein is composed of primarily alpha-helices and coiled coils. The structure is composed of very little beta sheets, a total of three areas demonstrate possible beta sheet structure.
The Tertiary structure of C8orf48 was obtained from the iTASSER program.
## Post-translational modifications
C8orf48 has various predicted post-translational modifications. These post-translational modifications include O-glycosylation, Glycation, N-linked glycosylation, Phosphorylation Sites, Yin-Yang sites, sumoylation, and SUMO interactions.
## Subcellular localization
PSORT II results determined that the protein C8orf48 does not have a signalPeptide as well as no transmembrane domains. The prediction is that C8orf48 is most likely nuclear and potentially cytoplasmic. When comparing orthologs of C8orf48 we see very similar results, the protein is predicted to be localized in the nucleus predominantly and secondly predicted to be localized in the cytoplasm. Further sub-cellular localization analysis was done through the use of CELLO. These results also support the notion that C8orf48 is localized in the nucleus.
# Homology
C8orf48 is conserved in mammals, amphibians, reptiles, aves, and fish. C8orf48 orthologs were unable to be found in bacteria, archea, plants, and fungi. There were no human paralogs found of C8orf48. Certain portions of the DUF 4606 domain is highly conserved in the orthologs.
# Expression
This gene has been found to be overly expressed in the tissues of the testis and colon muscle, as well as expressed in 76 developmental stages. C8orf48 has been found to be expressed most often in the bladder, bone, heart, larynx, testis, and thyroid. In regards to the developmental stages, C8orf48 was most often found in the embroid body.
## GEO profiles
In a study regarding multiple myeloma bone marrow mesenchymal stromal cells shows that the expression of C8orf48 is lower in the disease state cells in comparison to healthy cells. the opposite is demonstrated in the GeoProfile regarding Endometriosis, in this study, it was found that C8orf48 levels are higher in the disease state than in the healthy state. Other studies demonstrate differential expression of Papillary Thyroid cancer and Estrogen Receptor alpha-silenced MCF7 breast cancer cells. In control samples the levels of C8orf48 were lower than that of those with the Estrogen receptor knockdown.
# Regulation of expression
The transcription factors that act on C8orf48 are presented in Table 1. The majority of the transcription factors are involved in cell growth, proliferation, or regulation of cell migration. This implies that C8orf48 may play a role in the cell cycle. A few of the transcription factors presented themselves more than once, on both the positive and negative strand. These transcription factors include MAX binding protein and Estrogen-related receptor alpha (secondary DNA binding preference) both of which are involved in cell growth.
# Protein interactions
The proteins that interact with C8orf48 include Deleted In Liver Cancer 1 Protein (DLC1), MyoD Family Inhibitor (MDFI), Zinc Finger Protein 14 (ZNF14), and Sacroglycan Zeta (SGCZ). All of these protein interactions were found experimentally via a two-hybrid pooling approach, two-hybrid array, or two-hybrid screen.
# Clinical significance
C8orf48 has been found in studies regarding various types of carcinoma. Different C8orf48 expression levels have been found in Papillary Thyroid cancer and Estrogen Receptor alpha-silenced MCF7 breast cancer cells. | C8orf48
C8orf48 is a protein that in humans is encoded by the C8orf48 gene.[1] C8orf48 is a nuclear protein specifically predicted to be located in the nuclear lamina.[2][3] C8orf48 has been found to interact with proteins that are involved in the regulation of various cellular responses like gene expression, protein secretion, cell proliferation, and inflammatory responses.[4][5][6] This protein has been linked to breast cancer and papillary thyroid carcinoma.[7][8]
# Gene
C8orf48 is located on chromosome 8 (8p22) and spans from 13,566,843 to 13,568,288 on the positive strand.[9] C8orf48 has an exon count of 1 and no introns.[1][10] This protein does not have any isoforms nor exhibit any alternative splicing.
# Protein
The protein C8orf48 is 319 amino acids in length.[11] The molecular weight of this protein is 36.9 kDa and the isoelectric point is 8.86.[12] The C8orf48 protein is predicted to be a nuclear protein particularly located in the nuclear lamina.[2] This protein does not possess any signal peptides or transmembrane domains. This protein has also been found to be fairly abundant in humans.[13]
## Structure
C8orf48 protein has two predicted nuclear localization signals one spanning from 135-149 amino acids and the other from 204-221.[3] The secondary structure of C8orf48 protein is composed of primarily alpha-helices and coiled coils. The structure is composed of very little beta sheets, a total of three areas demonstrate possible beta sheet structure.[12]
The Tertiary structure of C8orf48 was obtained from the iTASSER program.
## Post-translational modifications
C8orf48 has various predicted post-translational modifications. These post-translational modifications include O-glycosylation, Glycation, N-linked glycosylation, Phosphorylation Sites, Yin-Yang sites, sumoylation, and SUMO interactions.[15]
## Subcellular localization
PSORT II results determined that the protein C8orf48 does not have a signalPeptide as well as no transmembrane domains.[16] The prediction is that C8orf48 is most likely nuclear and potentially cytoplasmic. When comparing orthologs of C8orf48 we see very similar results, the protein is predicted to be localized in the nucleus predominantly and secondly predicted to be localized in the cytoplasm. Further sub-cellular localization analysis was done through the use of CELLO.[17] These results also support the notion that C8orf48 is localized in the nucleus.
# Homology
C8orf48 is conserved in mammals, amphibians, reptiles, aves, and fish.[18] C8orf48 orthologs were unable to be found in bacteria, archea, plants, and fungi.[18] There were no human paralogs found of C8orf48. Certain portions of the DUF 4606 domain is highly conserved in the orthologs.
# Expression
This gene has been found to be overly expressed in the tissues of the testis and colon muscle, as well as expressed in 76 developmental stages.[19] C8orf48 has been found to be expressed most often in the bladder, bone, heart, larynx, testis, and thyroid.[20] In regards to the developmental stages, C8orf48 was most often found in the embroid body.[20]
## GEO profiles
In a study regarding multiple myeloma bone marrow mesenchymal stromal cells shows that the expression of C8orf48 is lower in the disease state cells in comparison to healthy cells.[21] the opposite is demonstrated in the GeoProfile regarding Endometriosis, in this study, it was found that C8orf48 levels are higher in the disease state than in the healthy state.[22] Other studies demonstrate differential expression of Papillary Thyroid cancer and Estrogen Receptor alpha-silenced MCF7 breast cancer cells. In control samples the levels of C8orf48 were lower than that of those with the Estrogen receptor knockdown.[7]
# Regulation of expression
The transcription factors that act on C8orf48 are presented in Table 1. The majority of the transcription factors are involved in cell growth, proliferation, or regulation of cell migration. This implies that C8orf48 may play a role in the cell cycle. A few of the transcription factors presented themselves more than once, on both the positive and negative strand. These transcription factors include MAX binding protein and Estrogen-related receptor alpha (secondary DNA binding preference) both of which are involved in cell growth.[23][24]
# Protein interactions
The proteins that interact with C8orf48 include Deleted In Liver Cancer 1 Protein (DLC1), MyoD Family Inhibitor (MDFI), Zinc Finger Protein 14 (ZNF14), and Sacroglycan Zeta (SGCZ).[4] All of these protein interactions were found experimentally via a two-hybrid pooling approach, two-hybrid array, or two-hybrid screen.[6]
# Clinical significance
C8orf48 has been found in studies regarding various types of carcinoma. Different C8orf48 expression levels have been found in Papillary Thyroid cancer and Estrogen Receptor alpha-silenced MCF7 breast cancer cells.[21][22] | https://www.wikidoc.org/index.php/C8orf48 | |
aa1f6eb3a95a779ec14106114cb3221e39b4e09c | wikidoc | C8orf58 | C8orf58
Chromosome 8 open reading frame 58 is an uncharacterised protein that in humans is encoded by the C8orf58 gene. The protein is predicted to be localized in the nucleus.
# Gene
The C8orf58 gene is located on chromosome 8 at position 8p21.3. It spans a total of 4,550 base pairs and has seven exons. C8orf58 is flanked by the genes PDLIM2 and CCAR2. There are no aliases. It is defined as a protein coding gene.
# mRNA
C8orf58 produces three transcript splice variants. The transcript of variant 1 represents the longest transcript and encodes the largest protein. It is 2,062 base pairs and contains seven exons. There are two other splice variants, produced by alternative splice sites.
C8orf58 has a relatively short 5’ region and a moderate 3’ region. Both the 5’ and 3’ regions contain stem loops. There is one predicted miRNA binding site that found in the 3’UTR of C8orf58.
# Protein
C8orf58 protein Isoform 1 is 365 amino acids long. Isoform 2 and Isoform 3 are 357 and 300 amino acids respectively. There is a kozak consensus sequence present, which confirms it is a protein coding sequence.
C8orf58 Isoform 1 has a molecular weight of 39.7 kDa and an isoelectric point of 8.29. It is proline and arginine rich and isoleucine, asparagine, phenylalanine, and tyrosine poor.
The predicted secondary structure of the C8orf58 protein include multiple alpha helices and one beta strands.
# Evolutionary history
It is part of the DUF4657 family, a family of proteins found in eukaryotes. Proteins in this family are typically between 305 and 370 amino acids in length. The Domain of Unknown Function (DUF) of C8orf58 is located between amino acids 73 to 364.
# Expression
According to the NCBI GEO profiles, C8orf58 is a narrowly expressed protein found in spleen, lung, thymus, prostate, and spinal cord tissue. It is constitutively expressed in these tissues.
# Post-translational modification
The bioinformatic tools on Expasy were used to determine potential post translational modification sites for the C8orf58 protein. There are two predicted phosphorylation sites and one predicted sumoylation site.
# Subcellular localization
According to PSORT II, C8orf58 is located in the nucleus. This is supported by the presence of a sumoylation site, which is involved in nucleic cytoplasmic transport.
# Interacting proteins
Two proteins have been found to interact with protein C8orf58, CENPH and metG1, which were found using two hybrid assay and the two hybrid pooling approach respectively. CENPH (Centromere Protein H) plays a critical role in centromere structure, kinetochore formation, and sister chromatid separation. MetG1 (Methionine—tRNA ligase) is required for elongation of protein synthesis and the initiation of all mRNA translation through initiator tRNA(fMet) aminoacylation.
# Homology
An important paralog of this gene is ENSG00000248235. Orthologs of the human gene C8orf58 are limited to vertebrates of the animal kingdom. | C8orf58
Chromosome 8 open reading frame 58 is an uncharacterised protein that in humans is encoded by the C8orf58 gene.[1] The protein is predicted to be localized in the nucleus.
# Gene
The C8orf58 gene is located on chromosome 8 at position 8p21.3. It spans a total of 4,550 base pairs and has seven exons. C8orf58 is flanked by the genes PDLIM2 and CCAR2.[2] There are no aliases. It is defined as a protein coding gene.[3]
# mRNA
C8orf58 produces three transcript splice variants. The transcript of variant 1 represents the longest transcript and encodes the largest protein. It is 2,062 base pairs and contains seven exons. There are two other splice variants, produced by alternative splice sites.[4]
C8orf58 has a relatively short 5’ region and a moderate 3’ region. Both the 5’ and 3’ regions contain stem loops.[5] There is one predicted miRNA binding site that found in the 3’UTR of C8orf58.[6]
# Protein
C8orf58 protein Isoform 1 is 365 amino acids long. Isoform 2 and Isoform 3 are 357 and 300 amino acids respectively. There is a kozak consensus sequence present, which confirms it is a protein coding sequence.[7]
C8orf58 Isoform 1 has a molecular weight of 39.7 kDa and an isoelectric point of 8.29. It is proline and arginine rich and isoleucine, asparagine, phenylalanine, and tyrosine poor.[8]
The predicted secondary structure of the C8orf58 protein include multiple alpha helices and one beta strands.[8][9]
# Evolutionary history
It is part of the DUF4657 family, a family of proteins found in eukaryotes. Proteins in this family are typically between 305 and 370 amino acids in length.[10] The Domain of Unknown Function (DUF) of C8orf58 is located between amino acids 73 to 364.
# Expression
According to the NCBI GEO profiles, C8orf58 is a narrowly expressed protein found in spleen, lung, thymus, prostate, and spinal cord tissue. It is constitutively expressed in these tissues.[11]
# Post-translational modification
The bioinformatic tools on Expasy were used to determine potential post translational modification sites for the C8orf58 protein. There are two predicted phosphorylation sites and one predicted sumoylation site.[12]
# Subcellular localization
According to PSORT II, C8orf58 is located in the nucleus. This is supported by the presence of a sumoylation site, which is involved in nucleic cytoplasmic transport.
# Interacting proteins
Two proteins have been found to interact with protein C8orf58, CENPH and metG1, which were found using two hybrid assay and the two hybrid pooling approach respectively.[13] CENPH (Centromere Protein H) plays a critical role in centromere structure, kinetochore formation, and sister chromatid separation.[14] MetG1 (Methionine—tRNA ligase) is required for elongation of protein synthesis and the initiation of all mRNA translation through initiator tRNA(fMet) aminoacylation.[15]
# Homology
An important paralog of this gene is ENSG00000248235.[16] Orthologs of the human gene C8orf58 are limited to vertebrates of the animal kingdom. | https://www.wikidoc.org/index.php/C8orf58 | |
506fbda508605e17f2bd7275c2bedf78051e4b3c | wikidoc | C9orf25 | C9orf25
Chromosome 9 open reading frame 25 (C9orf25) is a domain that encodes the FAM219A gene. The terms FAM219A and C9orf25 are aliases and can be used interchangeably. The function of this gene is not yet completely understood.
# Gene
## Location
In humans, C9orf25 is located at the 9p13.3 position on chromosome 9. The gene is encoded on the sense strand (-) spanning the chromosomal locus from base pair 34,502,909 to 34,398,027. The span of the gene is 104,882 base pairs
## Transcript variants
In humans there are 8 main transcript variants of the FAM219A gene. All of these transcripts have varying lengths and splice sites with transcript variant 1 being the longest and most abundant. Only four of these transcripts encode for a protein product.
# Homology
## Orthologs
The C9orf25 gene has orthologs in a wide variety of Eukaryotic organisms, including invertebrates. This gene has not been found in plants, fungi or protists. C9orf25 is a slowly evolving gene. It is also highly conserved through out all of its known orthologs.
## Paralogs
C9orf25 has a paralog FAM219B which is located on the long arm of chromosome 9 and is 198 amino acids long. The C9orf25 and FAM219B genes duplicated and diverged between 684 and 797 million years ago.
# Protein
## General properties
The C9orf25 protein is composed of 185 amino acids. It has a molecular weight of 20.4 kilodaltons and an isoelectric point of 4.47. It is a member of the FAM219 super family. The entire protein is still considered to be a domain of unknown function.
## Protein localization
C9orf25 has no signal sequence and remains in the cytosol.
## Conserved motifs and post-translational modifications
The following are experimental post-transitional modifications for the C9orf25 protein:
- 6 predicted Serine phosphorylation sites
- 1 predicted Tyrosine phosphorylation site
- 1 predicted prenylation site
## Secondary structure
The secondary structure of the gene is predicted to have two stretches of alpha helices and one beta strand. The majority of the secondary structure of gene is random coils.
## Expression
The C9orf25 gene has medium to high expression in most tissues of the body. The gene has particularly high expression in the nervous, digestive and male reproductive systems.
## Interacting proteins
The C9orf25 gene has many different interactions with a variety of other proteins that have an assortment of functions. The main ones that are listed on at least two reviewed sources are shown below.
# Clinical significance
The C9orf25 protein is associated with several disease causing proteins, however does not seem to be responsible for disease on its own. The gene seems to have higher expression in metastatic cells. | C9orf25
Chromosome 9 open reading frame 25 (C9orf25) is a domain that encodes the FAM219A gene.[1] The terms FAM219A and C9orf25 are aliases and can be used interchangeably. The function of this gene is not yet completely understood.
# Gene
## Location
In humans, C9orf25 is located at the 9p13.3 position on chromosome 9.[2] The gene is encoded on the sense strand (-) spanning the chromosomal locus from base pair 34,502,909 to 34,398,027.[1][3] The span of the gene is 104,882 base pairs[4][5][6][7][8][9][10]
## Transcript variants
In humans there are 8 main transcript variants of the FAM219A gene.[3] All of these transcripts have varying lengths and splice sites with transcript variant 1 being the longest and most abundant.[1][3] Only four of these transcripts encode for a protein product.[11]
# Homology
## Orthologs
The C9orf25 gene has orthologs in a wide variety of Eukaryotic organisms, including invertebrates. This gene has not been found in plants, fungi or protists.[13] C9orf25 is a slowly evolving gene.[12] It is also highly conserved through out all of its known orthologs.
## Paralogs
C9orf25 has a paralog FAM219B which is located on the long arm of chromosome 9 and is 198 amino acids long.[14] The C9orf25 and FAM219B genes duplicated and diverged between 684 and 797 million years ago.
# Protein
## General properties
The C9orf25 protein is composed of 185 amino acids. It has a molecular weight of 20.4 kilodaltons and an isoelectric point of 4.47.[15] It is a member of the FAM219 super family. The entire protein is still considered to be a domain of unknown function.
## Protein localization
C9orf25 has no signal sequence and remains in the cytosol.[15]
## Conserved motifs and post-translational modifications
The following are experimental post-transitional modifications for the C9orf25 protein:[16]
- 6 predicted Serine phosphorylation sites
- 1 predicted Tyrosine phosphorylation site
- 1 predicted prenylation site
## Secondary structure
The secondary structure of the gene is predicted to have two stretches of alpha helices and one beta strand. The majority of the secondary structure of gene is random coils.[17]
## Expression
The C9orf25 gene has medium to high expression in most tissues of the body.[18] The gene has particularly high expression in the nervous, digestive and male reproductive systems.[19]
## Interacting proteins
The C9orf25 gene has many different interactions with a variety of other proteins that have an assortment of functions.[20][21] The main ones that are listed on at least two reviewed sources are shown below.
# Clinical significance
The C9orf25 protein is associated with several disease causing proteins, however does not seem to be responsible for disease on its own.[2][11] The gene seems to have higher expression in metastatic cells.[18] | https://www.wikidoc.org/index.php/C9orf25 | |
d0b53aee756c0faf60ba95e800d1cec5301fbf58 | wikidoc | C9orf64 | C9orf64
C9orf64 (Chromosome 9 open reading frame 64) is a gene located on chromosome 9, that in humans encodes the protein queuosine salvage protein. The function and biological process of the queuosine salvage protein is not well understood by the scientific community, but some evidence from orthologs indicates it may be involved in tRNA processing. The most common mRNA contains 4 coding exons, and it has 2 additional alternatively spliced exons. C9orf64 has been found in 5 different splice variants.
Expression of this gene is highest in the duodenum and small intestine, and it is also expressed in 24 other tissues.
22 variants have been annotated in the NIH Database, ClinVar, linked to disease conditions such as seizures, developmental delay, and muscular hypotonia.
# Protein
Queuosine salvage protein is 341 amino acids long with a molecular weight of 39,029 Daltons and an isoelectric point of 5.61. It is a member of the DUF2419 superfamily. The DUF position on the human protein is from amino acid 53 to 341.
Bioinformatic tools at ExPASy predicted a second peroxisomal targeting signal.
# Gene locus
C9orf64 is located on chromosome 9q21.32. The genes closest to C9orf64 on the long arm of chromosome 9 include GKAP1, KIF27, HNRNPK, RMI1, and a MicroRNA MIR7-1.
# Homology
C9orf64 is only found in eukaryotes. Orthologs have been found from primates to fungi and plants. | C9orf64
C9orf64 (Chromosome 9 open reading frame 64) is a gene located on chromosome 9, that in humans encodes the protein queuosine salvage protein.[1] The function and biological process of the queuosine salvage protein is not well understood by the scientific community, but some evidence from orthologs indicates it may be involved in tRNA processing. The most common mRNA contains 4 coding exons, and it has 2 additional alternatively spliced exons.[1] C9orf64 has been found in 5 different splice variants.[2]
Expression of this gene is highest in the duodenum and small intestine, and it is also expressed in 24 other tissues. [3]
22 variants have been annotated in the NIH Database, ClinVar, linked to disease conditions such as seizures, developmental delay, and muscular hypotonia.[4]
# Protein
Queuosine salvage protein is 341 amino acids long with a molecular weight of 39,029 Daltons and an isoelectric point of 5.61. It is a member of the DUF2419 superfamily.[5][6] The DUF position on the human protein is from amino acid 53 to 341.[5]
Bioinformatic tools at ExPASy predicted a second peroxisomal targeting signal.[7]
# Gene locus
C9orf64 is located on chromosome 9q21.32.[1] The genes closest to C9orf64 on the long arm of chromosome 9 include GKAP1, KIF27, HNRNPK, RMI1, and a MicroRNA MIR7-1.[8]
# Homology
C9orf64 is only found in eukaryotes. Orthologs have been found from primates to fungi and plants.[6] | https://www.wikidoc.org/index.php/C9orf64 | |
53d0da6c3c598bd6c9e36460af999b27cc6dd461 | wikidoc | C9orf72 | C9orf72
C9orf72 (chromosome 9 open reading frame 72) is a protein which in humans is encoded by the gene C9orf72.
The human C9orf72 gene is located on the short (p) arm of chromosome 9 open reading frame 72, from base pair 27,546,542 to base pair 27,573,863. Its cytogenetic location is at 9p21.2.
The protein is found in many regions of the brain, in the cytoplasm of neurons as well as in presynaptic terminals. Disease-causing mutations in the gene were first discovered by two independent research teams, led by Rosa Rademakers of Mayo Clinic and Bryan Traynor of the National Institutes of Health, and were first reported in October 2011. The mutations in C9orf72 are significant because it is the first pathogenic mechanism identified to be a genetic link between familial frontotemporal dementia (FTD) and of amyotrophic lateral sclerosis (ALS). As of 2012, it is the most common mutation identified that is associated with familial FTD and/or ALS.
# Gene location
Cytogenetic Location: 9p21.2
Molecular Location on chromosome 9: base pairs 27,546,542 to 27,573,863
The C9orf72 gene is located on the short (p) arm of chromosome 9 at position 21.2.
More precisely, the C9orf72 gene is located from base pair 27,546,542 to base pair 27,573,863 on chromosome 9.
# Mutations
The mutation of C9ORF72 is a hexanucleotide repeat expansion of the six letter string of nucleotides GGGGCC. In a normal person, there are few repeats of this hexanucleotide, typically less than 20-30, but in people with the mutation, the repeat can occur in the order of hundreds. It is known that the mutation interferes with normal expression of the protein made by C9orf72, however the function of this protein remains speculative. There are two major theories about the way that the C9ORF72 mutation causes FTD and/or ALS. One theory is that accumulation of RNA in the nucleus and cytoplasm becomes toxic, and RNA binding protein sequestration occurs. The other is that the lack of half of the C9ORF72 protein (Haploinsufficiency) in the body causes the diseases. Additionally, RNA transcribed from the C9ORF72 gene, containing expanded GGGGCC repeats, is translated through a non-ATG initiated mechanism. This drives the formation and accumulation of dipeptide repeat proteins corresponding multiple ribosomal reading frames on the mutation. The GGGGCC repeat expansion in C9orf72 is believed to compromise nucleocytoplasmic transport through several possible mechanisms.
# Clinical significance
The C9ORF72 mutation is the first mutation found to be a link between familial FTD and ALS. Numerous published studies have confirmed the commonality of the C9ORF72 repeat expansion in FTD and ALS, which are both diseases without cures that have affected millions of people. Frontotemporal dementia is the second most common form of early-onset dementia after Alzheimer’s disease in people under the age of 65. Amyotrophic lateral sclerosis is also devastating; it is characterized by motor neuron degeneration that eventually causes respiratory failure with a median survival of three years after onset.
C9orf72 is present in approximately 40% of familial ALS and 8-10 % of sporadic ALS. It is currently the most common demonstrated mutation related to ALS - far more common than SOD1 or TDP-43.
While different mutations of various genes have been linked to different phenotypes of FTD in the past, C9orf72 specifically has been linked to behavioral variant FTD. Certain pathology in FTD caused by the C9orf72 mutation can also include:
- TDP-43 in all C9 carriers
- Ubiquitin-binding protein 62
C9ORF72 is specifically linked to familial ALS, which affects about 10% of ALS patients. Traditionally, familial and sporadic cases of ALS have been clinically indistinguishable, which has made diagnosis difficult. The identification of this gene will therefore help in the future diagnosis of familial ALS.
Slow diagnosis is also common for FTD, which can often take up to a year with many patients initially misdiagnosed with another condition. Testing for a specific gene that is known to cause the diseases would help with faster diagnoses. Possibly most importantly, the identification of this hexanucleotide repeat expansion is an extremely promising avenue for possible future therapies of both familial FTD and familial ALS, once the mechanism and function of the C9ORF72 protein is better comprehended. Furthermore, present research is being done to see if there is a correlation between C9ORF72 and other neurological diseases, such as motor neuron disease and Huntington's disease.
# Gene heritability
It is possible that genetic anticipation may exist for this mutation. However, only 1 in 4 families exhibited significant anticipation in this study (n=63) It has been proposed that the amount of the repeat expansion increases with each successive generation, possibly causing the disease to be more severe in the next generation, showing onset up to a decade earlier with each successive generation after the carrier. The buildup of a repeat expansion with each generation is typically thought to occur because the DNA is unstable and therefore accumulates exponentially every time the gene is copied. No genetic evidence for this has yet been demonstrated for this mutation. There is also a demographic factor that should be considered in genetic predisposition, as some cohorts have found that there might be a founder effect for the C9orf72 mutation, which might have led to higher frequencies of the mutation in specific populations than others. Specifically this founder has been linked to Northern Europeans populations, namely Finland.
## Gene testing
Since this mutation has been found to be the most common mutation identified in familial FTD and/or ALS, it is considered one of if not the most dependable candidates for genetic testing. Patients are considered eligible if the mother or father has had FTD and/or another family member has had ALS. There are also population and location risk factors in determining eligibility. Some studies have found that the mutation has a higher frequency in certain cohorts. Athena Diagnostics (Quest Diagnostics) announced in Spring 2012 the first clinically available testing service for detecting the hexanucleotide repeat expansion in the C9orf72 gene. Genetic counseling is recommended for the patients before a genetic test is ordered.
# Likely function
C9ORF72 is a full-length homologue of DENN proteins (where DENN stands for "differentially expressed in normal and neoplastic cells"). These proteins have a conserved DENN module consisting of an N-terminal longin domain, followed by the central DENN and C-terminal alpha-helical d-DENN domains. This has led to DENNL72 being suggested as a new name for C9orf72.
Given the molecular role of known DENN modules, the C9ORF72-like proteins are predicted to function as Guanine nucleotide exchange factors for small GTPases, most likely a Rab. A recent study provided the first experimental evidence to confirm this: C9ORF72 was found to regulate endosomal trafficking and autophagy in neuronal cells and primary neurons. This suggests that certain aspects of the ALS and FTD disease pathology might result from haploinsufficiency of C9ORF72/DENNL72, leading to a defect in intracellular membrane traffic, either exocytosis or endocytosis, in addition to the strong possibility of RNA-mediated toxicity.
## DNA damage response
Repeat sequence expansion mutations in C9orf72 that lead to neurodegeneration in ALS/FTD display dysfunction of the nucleolus and of R-loop formation. Such dysfunctions can lead to DNA damage. Motor neurons with C9orf72 mutations were found to activate the DNA damage response (DDR) as indicated by up-regulation of DDR markers. If the DDR is insufficient to repair these DNA damages, apoptosis of the motor neurons is the likely result.
# Evolutionary history
Sequence analysis further suggests that the C9ORF72 protein emerged early in eukaryotic evolution, and whereas most eukaryotes usually possess a single copy of the gene encoding the C9ORF72 protein, the eukaryotes Entamoeba and Trichomonas vaginalis possess multiple copies, suggestive of independent lineage-specific expansions in these species. The family is lost in most fungi (except Rhizopus) and plants.
# Implications for future therapies
Overall, the C9ORF72 mutation holds great promise for future therapies for familial FTD and/or ALS to be developed. Currently, there is focus on more research to be done on C9ORF72 to further understand the exact mechanisms involved in the cause of the diseases by this mutation. A clearer understanding of the exact pathogenic mechanism will aid in a more focused drug therapies. Possible drug targets currently include the repeat expansion itself as well as increasing levels of C9ORF72. Blocking the toxic gain of RNA foci to prevent RNA sequestration might be helpful as well as making up for the lack of C9ORF72. Either of these targets as well as a combination of them might be promising future targets in minimizing the effects of the C9ORF72 repeat expansion.
# Interactions
C9ORF72 has been shown to interact with:
- ELAVL1,
- UBC, and
- ADARB2 | C9orf72
C9orf72 (chromosome 9 open reading frame 72) is a protein which in humans is encoded by the gene C9orf72.
The human C9orf72 gene is located on the short (p) arm of chromosome 9 open reading frame 72, from base pair 27,546,542 to base pair 27,573,863. Its cytogenetic location is at 9p21.2.[1]
The protein is found in many regions of the brain, in the cytoplasm of neurons as well as in presynaptic terminals. Disease-causing mutations in the gene were first discovered by two independent research teams, led by Rosa Rademakers of Mayo Clinic and Bryan Traynor of the National Institutes of Health, and were first reported in October 2011.[2][3] The mutations in C9orf72 are significant because it is the first pathogenic mechanism identified to be a genetic link between familial frontotemporal dementia (FTD) and of amyotrophic lateral sclerosis (ALS). As of 2012, it is the most common mutation identified that is associated with familial FTD and/or ALS.
# Gene location
Cytogenetic Location: 9p21.2
Molecular Location on chromosome 9: base pairs 27,546,542 to 27,573,863
The C9orf72 gene is located on the short (p) arm of chromosome 9 at position 21.2.
More precisely, the C9orf72 gene is located from base pair 27,546,542 to base pair 27,573,863 on chromosome 9.[4]
# Mutations
The mutation of C9ORF72 is a hexanucleotide repeat expansion of the six letter string of nucleotides GGGGCC.[5] In a normal person, there are few repeats of this hexanucleotide, typically less than 20-30,[6] but in people with the mutation, the repeat can occur in the order of hundreds.[7] It is known that the mutation interferes with normal expression of the protein made by C9orf72, however the function of this protein remains speculative. There are two major theories about the way that the C9ORF72 mutation causes FTD and/or ALS. One theory is that accumulation of RNA in the nucleus and cytoplasm becomes toxic, and RNA binding protein sequestration occurs. The other is that the lack of half of the C9ORF72 protein (Haploinsufficiency) in the body causes the diseases. Additionally, RNA transcribed from the C9ORF72 gene, containing expanded GGGGCC repeats, is translated through a non-ATG initiated mechanism. This drives the formation and accumulation of dipeptide repeat proteins corresponding multiple ribosomal reading frames on the mutation.[8][9] The GGGGCC repeat expansion in C9orf72 is believed to compromise nucleocytoplasmic transport through several possible mechanisms.[10]
# Clinical significance
The C9ORF72 mutation is the first mutation found to be a link between familial FTD and ALS.[11] Numerous published studies have confirmed the commonality of the C9ORF72 repeat expansion in FTD and ALS, which are both diseases without cures that have affected millions of people. Frontotemporal dementia is the second most common form of early-onset dementia after Alzheimer’s disease in people under the age of 65.[12] Amyotrophic lateral sclerosis is also devastating; it is characterized by motor neuron degeneration that eventually causes respiratory failure with a median survival of three years after onset.[13]
C9orf72 is present in approximately 40% of familial ALS and 8-10 % of sporadic ALS. It is currently the most common demonstrated mutation related to ALS - far more common than SOD1 or TDP-43.
While different mutations of various genes have been linked to different phenotypes of FTD in the past, C9orf72 specifically has been linked to behavioral variant FTD.[14] Certain pathology in FTD caused by the C9orf72 mutation can also include:
- TDP-43 in all C9 carriers[15]
- Ubiquitin-binding protein 62[16]
C9ORF72 is specifically linked to familial ALS, which affects about 10% of ALS patients. Traditionally, familial and sporadic cases of ALS have been clinically indistinguishable, which has made diagnosis difficult. The identification of this gene will therefore help in the future diagnosis of familial ALS.[13]
Slow diagnosis is also common for FTD, which can often take up to a year with many patients initially misdiagnosed with another condition. Testing for a specific gene that is known to cause the diseases would help with faster diagnoses. Possibly most importantly, the identification of this hexanucleotide repeat expansion is an extremely promising avenue for possible future therapies of both familial FTD and familial ALS, once the mechanism and function of the C9ORF72 protein is better comprehended. Furthermore, present research is being done to see if there is a correlation between C9ORF72 and other neurological diseases, such as motor neuron disease and Huntington's disease.[17][18]
# Gene heritability
It is possible that genetic anticipation may exist for this mutation. However, only 1 in 4 families exhibited significant anticipation in this study (n=63) [15] It has been proposed that the amount of the repeat expansion increases with each successive generation, possibly causing the disease to be more severe in the next generation, showing onset up to a decade earlier with each successive generation after the carrier. The buildup of a repeat expansion with each generation is typically thought to occur because the DNA is unstable and therefore accumulates exponentially every time the gene is copied. No genetic evidence for this has yet been demonstrated for this mutation.[19] There is also a demographic factor that should be considered in genetic predisposition, as some cohorts have found that there might be a founder effect for the C9orf72 mutation, which might have led to higher frequencies of the mutation in specific populations than others. Specifically this founder has been linked to Northern Europeans populations, namely Finland.[14]
## Gene testing
Since this mutation has been found to be the most common mutation identified in familial FTD and/or ALS, it is considered one of if not the most dependable candidates for genetic testing. Patients are considered eligible if the mother or father has had FTD and/or another family member has had ALS.[13] There are also population and location risk factors in determining eligibility. Some studies have found that the mutation has a higher frequency in certain cohorts.[20] Athena Diagnostics (Quest Diagnostics) announced in Spring 2012 the first clinically available testing service for detecting the hexanucleotide repeat expansion in the C9orf72 gene.[21] Genetic counseling is recommended for the patients before a genetic test is ordered.
# Likely function
C9ORF72 is a full-length homologue of DENN proteins (where DENN stands for "differentially expressed in normal and neoplastic cells").[22][23][24] These proteins have a conserved DENN module consisting of an N-terminal longin domain, followed by the central DENN and C-terminal alpha-helical d-DENN domains.[23] This has led to DENNL72 being suggested as a new name for C9orf72.[24]
Given the molecular role of known DENN modules,[25] the C9ORF72-like proteins are predicted to function as Guanine nucleotide exchange factors for small GTPases, most likely a Rab. A recent study provided the first experimental evidence to confirm this: C9ORF72 was found to regulate endosomal trafficking and autophagy in neuronal cells and primary neurons.[23][26] This suggests that certain aspects of the ALS and FTD disease pathology might result from haploinsufficiency of C9ORF72/DENNL72, leading to a defect in intracellular membrane traffic, either exocytosis or endocytosis, in addition to the strong possibility of RNA-mediated toxicity.
## DNA damage response
Repeat sequence expansion mutations in C9orf72 that lead to neurodegeneration in ALS/FTD display dysfunction of the nucleolus and of R-loop formation. Such dysfunctions can lead to DNA damage. Motor neurons with C9orf72 mutations were found to activate the DNA damage response (DDR) as indicated by up-regulation of DDR markers.[27] If the DDR is insufficient to repair these DNA damages, apoptosis of the motor neurons is the likely result.
# Evolutionary history
Sequence analysis further suggests that the C9ORF72 protein emerged early in eukaryotic evolution, and whereas most eukaryotes usually possess a single copy of the gene encoding the C9ORF72 protein, the eukaryotes Entamoeba and Trichomonas vaginalis possess multiple copies, suggestive of independent lineage-specific expansions in these species. The family is lost in most fungi (except Rhizopus) and plants.[23][24]
# Implications for future therapies
Overall, the C9ORF72 mutation holds great promise for future therapies for familial FTD and/or ALS to be developed. Currently, there is focus on more research to be done on C9ORF72 to further understand the exact mechanisms involved in the cause of the diseases by this mutation. A clearer understanding of the exact pathogenic mechanism will aid in a more focused drug therapies. Possible drug targets currently include the repeat expansion itself as well as increasing levels of C9ORF72. Blocking the toxic gain of RNA foci to prevent RNA sequestration might be helpful as well as making up for the lack of C9ORF72. Either of these targets as well as a combination of them might be promising future targets in minimizing the effects of the C9ORF72 repeat expansion.[28]
# Interactions
C9ORF72 has been shown to interact with:
- ELAVL1,[29]
- UBC,[29] and
- ADARB2[30] | https://www.wikidoc.org/index.php/C9orf72 | |
c81af0530c9bb253f4aa2488be9a3b23bd60aa4c | wikidoc | C9orf84 | C9orf84
Uncharacterized protein C9orf84, also known as C9orf84, is a protein that in humans is encoded by the C9orf84 gene, which stands for Chromosome 9 open reading frame 84.
# Gene
The chromosomal locus of C9orf84 is 9q31.3, which it shares with at least 115 other protein encoding genes, and it is located on the negative strand. In humans it contains 34 exons, and it is 108,834 base pairs long, including introns and exons. C9orf84 is located between the protein encoding genes GNG10 and UGCG. When this gene is transcribed in humans, it most often forms a mRNA which is 4,721 base pairs long and contains 26 exons. There are at least 13 alternate splice forms of C9orf84, with more predicted.
# Protein
C9orf84 in humans has at least 6 alternate isoforms, with at least 10 more predicted. The primarily used sequence in humans is C9orf84 Isoform 1. This isoform is 1444 aa long, contains 26 exons, has a predicted molecular weight of 165.190 kDa, and a predicted pI of 5.10.
C9orf84 has been show to undergo phosphorylation. It is predicted that C9orf84 undergoes several other post-translational modifications, including glycosylation and o-linked glycosylation, and it contains leucine-rich nuclear export signals. Compared to the generic reference set swp23s.q, the primary structure of the protein is deficient in the amino acid grouping AGP (alanine, glycine, proline), and contains more acidic amino acids (glutamate, aspartate) than basic amino acids (lysine, arginine). This is true for the protein in all vertebrates. In the human Isoform 1, there have been 220 identified single nucleotide polymorphisms detected in the coding region, but none have currently been linked to human disease. The secondary structure of this protein is predicted to be mainly alpha-helices in roughly the first two thirds of the protein, and coils in the last third. It is predicted that this protein is localized in the nucleus.
## Expression
C9orf84 is ubiquitously expressed in most tissues with higher than average expression in the testes, the kidney, the thymus, and the adrenal gland.
The promoter for C9orf84 Isoform 1 in humans is 639 bp long and overlaps with the 5’ untranslated region of the gene. There are four alternate promoters that promote different transcript variants.
# = Interactions
C9orf84 has been experimentally determined, through a two hybrid pooling approach, to interact with methionine aminopeptidase, a protein encoded by the maP3 gene in Bacillus anthracis.
Several of the most common and most conserved transcription factor binding sites families that are predicted to be found in C9orf84’s promoter region are ETS1 factors, Ccaat/Enhancer Binding Proteins, and Lymphoid enhancer-binding factor 1. ETS1, Ccaat-enhancer-binding proteins, and Lymphoid enhancer-binding factor 1 are all related to immunity.
# Evolutionary History
C9orf84 is the only gene in the human genome with its particular sequence. This gene is found in all vertebrates, and some invertebrates. The most distant ortholog detectable by NCBI BLAST is in Nematostella vectensis (starlet sea anemone). The closest plant ortholog to C9orf84 is the SHOC1 protein in Arabidopsis thaliana. C9orf84 is not very well conserved even among mammals.
# Clinical Significance
C9orf84 is highly upregulated in psoriasis patients with lesional skin as opposed to psoriasis patients with non-lesional skin and non-psoriasis patients. | C9orf84
Uncharacterized protein C9orf84, also known as C9orf84, is a protein that in humans is encoded by the C9orf84 gene, which stands for Chromosome 9 open reading frame 84.
# Gene
The chromosomal locus of C9orf84 is 9q31.3, which it shares with at least 115 other protein encoding genes, and it is located on the negative strand.[1][2] In humans it contains 34 exons, and it is 108,834 base pairs long, including introns and exons. C9orf84 is located between the protein encoding genes GNG10 and UGCG. When this gene is transcribed in humans, it most often forms a mRNA which is 4,721 base pairs long and contains 26 exons. There are at least 13 alternate splice forms of C9orf84, with more predicted.[3]
# Protein
C9orf84 in humans has at least 6 alternate isoforms, with at least 10 more predicted.[4] The primarily used sequence in humans is C9orf84 Isoform 1. This isoform is 1444 aa long, contains 26 exons, has a predicted molecular weight of 165.190 kDa, and a predicted pI of 5.10.[5]
C9orf84 has been show to undergo phosphorylation.[6] It is predicted that C9orf84 undergoes several other post-translational modifications, including glycosylation and o-linked glycosylation, and it contains leucine-rich nuclear export signals.[7][8][9] Compared to the generic reference set swp23s.q, the primary structure of the protein is deficient in the amino acid grouping AGP (alanine, glycine, proline), and contains more acidic amino acids (glutamate, aspartate) than basic amino acids (lysine, arginine).[10] This is true for the protein in all vertebrates. In the human Isoform 1, there have been 220 identified single nucleotide polymorphisms detected in the coding region, but none have currently been linked to human disease.[11] The secondary structure of this protein is predicted to be mainly alpha-helices in roughly the first two thirds of the protein, and coils in the last third.[12] It is predicted that this protein is localized in the nucleus.[13]
## Expression
C9orf84 is ubiquitously expressed in most tissues with higher than average expression in the testes, the kidney, the thymus, and the adrenal gland.[14][15]
The promoter for C9orf84 Isoform 1 in humans is 639 bp long and overlaps with the 5’ untranslated region of the gene. There are four alternate promoters that promote different transcript variants.[16]
# = Interactions
=
C9orf84 has been experimentally determined, through a two hybrid pooling approach, to interact with methionine aminopeptidase, a protein encoded by the maP3 gene in Bacillus anthracis.[17]
Several of the most common and most conserved transcription factor binding sites families that are predicted to be found in C9orf84’s promoter region are ETS1 factors, Ccaat/Enhancer Binding Proteins, and Lymphoid enhancer-binding factor 1.[18] ETS1, Ccaat-enhancer-binding proteins, and Lymphoid enhancer-binding factor 1 are all related to immunity.
# Evolutionary History
C9orf84 is the only gene in the human genome with its particular sequence.[19] This gene is found in all vertebrates, and some invertebrates. The most distant ortholog detectable by NCBI BLAST is in Nematostella vectensis (starlet sea anemone).[20] The closest plant ortholog to C9orf84 is the SHOC1 protein in Arabidopsis thaliana.[21] C9orf84 is not very well conserved even among mammals.
# Clinical Significance
C9orf84 is highly upregulated in psoriasis patients with lesional skin as opposed to psoriasis patients with non-lesional skin and non-psoriasis patients.[22] | https://www.wikidoc.org/index.php/C9orf84 | |
392d6a5ab36f5c359bb42769efd26376c4285966 | wikidoc | CA-19-9 | CA-19-9
# Overview
CA-19-9 is a tumor marker.
# Interpretation
CA 19-9 is elevated in most patients with advanced pancreatic cancer, but it may also be elevated in other cancers, conditions, and diseases such as colorectal cancer, lung cancer, gallbladder cancer, gallstones, pancreatitis, cystic fibrosis, and liver disease.
Other causes of bile duct obstruction may also cause very high CA 19-9 levels, which fall when the blockage is cleared.
If the bile ducts are blocked, wait a week or two after the blockage is removed or treated to check CA 19-9 levels.
# Differential Diagnosis
In alphabetical order.
## Increased level of CA-19-9
### Malignant Diseases
- Biliary tract carcinoma
- Breast Cancer
- Bronchial carcinoma
- Colorectal Cancer
- Gastric carcinoma
- Liver carcinoma
- Ovarian Cancer
- Pancreatic Cancer
- Uterine Cancer
### Non-Malignant Diseases
- Cholecystitis
- Choledocholithiasis
- Cirrhosis
- Pancreatitis
- Pleural Effusions
# Related chapters
- CA 19-9 | CA-19-9
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
# Overview
CA-19-9 is a tumor marker.
# Interpretation
CA 19-9 is elevated in most patients with advanced pancreatic cancer, but it may also be elevated in other cancers, conditions, and diseases such as colorectal cancer, lung cancer, gallbladder cancer, gallstones, pancreatitis, cystic fibrosis, and liver disease.
Other causes of bile duct obstruction may also cause very high CA 19-9 levels, which fall when the blockage is cleared.
If the bile ducts are blocked, wait a week or two after the blockage is removed or treated to check CA 19-9 levels.
# Differential Diagnosis
In alphabetical order. [1] [2]
## Increased level of CA-19-9
### Malignant Diseases
- Biliary tract carcinoma
- Breast Cancer
- Bronchial carcinoma
- Colorectal Cancer
- Gastric carcinoma
- Liver carcinoma
- Ovarian Cancer
- Pancreatic Cancer
- Uterine Cancer
### Non-Malignant Diseases
- Cholecystitis
- Choledocholithiasis
- Cirrhosis
- Pancreatitis
- Pleural Effusions
# Related chapters
- CA 19-9 | https://www.wikidoc.org/index.php/CA-19-9 | |
da5f77a0547904a2f4957a7a9eeb6a74f5572c2b | wikidoc | CACNA1G | CACNA1G
Calcium channel, voltage-dependent, T type, alpha 1G subunit, also known as CACNA1G or Cav3.1 is a protein which in humans is encoded by the CACNA1G gene.
# Function
Voltage-dependent calcium channels can be distinguished based on their voltage-dependence, deactivation, and single-channel conductance. Low-voltage-activated calcium channels are referred to as 'T' type because their currents are both transient, owing to fast inactivation, and tiny, owing to small conductance. T-type channels are thought to be involved in pacemaker activity, low-threshold calcium spikes, neuronal oscillations and resonance, and rebound burst firing.
# Interactive pathway map
Click on genes, proteins and metabolites below to link to respective Wikipedia articles.
- ↑ The interactive pathway map can be edited at WikiPathways: "NicotineActivityonChromaffinCells_WP1603"..mw-parser-output cite.citation{font-style:inherit}.mw-parser-output q{quotes:"\"""\"""'""'"}.mw-parser-output code.cs1-code{color:inherit;background:inherit;border:inherit;padding:inherit}.mw-parser-output .cs1-lock-free a{background:url("")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-limited a,.mw-parser-output .cs1-lock-registration a{background:url("")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-subscription a{background:url("")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration{color:#555}.mw-parser-output .cs1-subscription span,.mw-parser-output .cs1-registration span{border-bottom:1px dotted;cursor:help}.mw-parser-output .cs1-hidden-error{display:none;font-size:100%}.mw-parser-output .cs1-visible-error{display:none;font-size:100%}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration,.mw-parser-output .cs1-format{font-size:95%}.mw-parser-output .cs1-kern-left,.mw-parser-output .cs1-kern-wl-left{padding-left:0.2em}.mw-parser-output .cs1-kern-right,.mw-parser-output .cs1-kern-wl-right{padding-right:0.2em} | CACNA1G
Calcium channel, voltage-dependent, T type, alpha 1G subunit, also known as CACNA1G or Cav3.1 is a protein which in humans is encoded by the CACNA1G gene.[1][2][3]
# Function
Voltage-dependent calcium channels can be distinguished based on their voltage-dependence, deactivation, and single-channel conductance. Low-voltage-activated calcium channels are referred to as 'T' type because their currents are both transient, owing to fast inactivation, and tiny, owing to small conductance. T-type channels are thought to be involved in pacemaker activity, low-threshold calcium spikes, neuronal oscillations and resonance, and rebound burst firing.[1]
# Interactive pathway map
Click on genes, proteins and metabolites below to link to respective Wikipedia articles. [§ 1]
- ↑ The interactive pathway map can be edited at WikiPathways: "NicotineActivityonChromaffinCells_WP1603"..mw-parser-output cite.citation{font-style:inherit}.mw-parser-output q{quotes:"\"""\"""'""'"}.mw-parser-output code.cs1-code{color:inherit;background:inherit;border:inherit;padding:inherit}.mw-parser-output .cs1-lock-free a{background:url("https://upload.wikimedia.org/wikipedia/commons/thumb/6/65/Lock-green.svg/9px-Lock-green.svg.png")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-limited a,.mw-parser-output .cs1-lock-registration a{background:url("https://upload.wikimedia.org/wikipedia/commons/thumb/d/d6/Lock-gray-alt-2.svg/9px-Lock-gray-alt-2.svg.png")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-subscription a{background:url("https://upload.wikimedia.org/wikipedia/commons/thumb/a/aa/Lock-red-alt-2.svg/9px-Lock-red-alt-2.svg.png")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration{color:#555}.mw-parser-output .cs1-subscription span,.mw-parser-output .cs1-registration span{border-bottom:1px dotted;cursor:help}.mw-parser-output .cs1-hidden-error{display:none;font-size:100%}.mw-parser-output .cs1-visible-error{display:none;font-size:100%}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration,.mw-parser-output .cs1-format{font-size:95%}.mw-parser-output .cs1-kern-left,.mw-parser-output .cs1-kern-wl-left{padding-left:0.2em}.mw-parser-output .cs1-kern-right,.mw-parser-output .cs1-kern-wl-right{padding-right:0.2em} | https://www.wikidoc.org/index.php/CACNA1G | |
19e2b1bdd9f20bec8c5e39ad6259d2d88a415954 | wikidoc | CACNA1H | CACNA1H
Calcium channel, voltage-dependent, T type, alpha 1H subunit, also known as CACNA1H, is a protein which in humans is encoded by the CACNA1H gene.
# Function
This gene encodes Cav3.2, a T-type member of the α1 subunit family, a protein in the voltage-dependent calcium channel complex. Calcium channels mediate the influx of calcium ions into the cell upon membrane polarization and consist of a complex of α1, α2δ, β, and γ subunits in a 1:1:1:1 ratio. The α1 subunit has 24 transmembrane segments and forms the pore through which ions pass into the cell. There are multiple isoforms of each of the proteins in the complex, either encoded by different genes or the result of alternative splicing of transcripts. Alternate transcriptional splice variants, encoding different isoforms, have been characterized for the gene described here.
# Clinical significance
Studies suggest certain mutations in this gene lead to childhood absence epilepsy (CAE). Variants of Cav3.2 with increased channel activity contribute to susceptibility to idiopathic generalized epilepsy (IGE), but are not sufficient to induce epilepsy on their own. The SFARIgene database lists CACNA1H with an autism score of 2.1, indicating a candidate causal relationship with autism. | CACNA1H
Calcium channel, voltage-dependent, T type, alpha 1H subunit, also known as CACNA1H, is a protein which in humans is encoded by the CACNA1H gene.[1][2][3]
# Function
This gene encodes Cav3.2, a T-type member of the α1 subunit family, a protein in the voltage-dependent calcium channel complex. Calcium channels mediate the influx of calcium ions into the cell upon membrane polarization and consist of a complex of α1, α2δ, β, and γ subunits in a 1:1:1:1 ratio. The α1 subunit has 24 transmembrane segments and forms the pore through which ions pass into the cell. There are multiple isoforms of each of the proteins in the complex, either encoded by different genes or the result of alternative splicing of transcripts. Alternate transcriptional splice variants, encoding different isoforms, have been characterized for the gene described here.[1]
# Clinical significance
Studies suggest certain mutations in this gene lead to childhood absence epilepsy (CAE).[4] Variants of Cav3.2 with increased channel activity contribute to susceptibility to idiopathic generalized epilepsy (IGE), but are not sufficient to induce epilepsy on their own.[5] The SFARIgene database lists CACNA1H with an autism score of 2.1, indicating a candidate causal relationship with autism. | https://www.wikidoc.org/index.php/CACNA1H | |
b2c21609ba2f4bc2fd4f3522b47cc315c2242785 | wikidoc | CADASIL | CADASIL
CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy) is the most common form of hereditary stroke disorder, and is thought to be caused by mutations of the Notch 3 gene on chromosome 19. The most common clinical manifestations are transient ischemic attacks or strokes, which usually occur between 40 and 50 years of age, although MRI is able to detect signs of the disease years prior to clinical manifestation of disease.
# Pathophysiology
The underlying pathology of CADASIL is progressive degeneration of the smooth muscle cells in blood vessels. Mutations in the Notch 3 gene (on the short arm of chromosome 19) cause an abnormal accumulation of Notch 3 at the cytoplasmic membrane of vascular smooth-muscle cells both in cerebral and extracerebral vessels, seen as granular osmiophilic deposits on electron microscopy.
Interestingly, the Notch 3 gene is in the same locus as the gene for familial hemiplegic migraine.
# Clinical Features
CADASIL may start with attacks of migraine with aura or subcortical transient ischemic attacks or strokes, or mood disorders between 35 to 55 years of age. The disease progresses to subcortical dementia associated with pseudobulbar palsy and .
# Diagnosis
MRI is the diagnostic modality of choice. Hypointensities on T1-weighted images and hyperintensities on T2-weighted images, usually multiple confluent white matter lesions of various sizes, are characteristic. These lesions are concentrated around the basal ganglia, periventricular white matter, and the pons, and are similar to those seen in Binswanger disease. These white matter lesions are also seen in asymptomatic individuals with the mutated gene.
The disease may also be diagnosed by screening for the mutated Notch 3 gene; however, this method is costly and laborious. Since CADASIL is a systemic arteriopathy, evidence of blood vessel damage is seen in small- and medium-sized arteries. It has therefore been suggested that skin biopsies could be used for diagnosis; however, the lack of widespread availability of a monoclonal antibody required for diagnosis, limit the utility of this method.
# Clinical Course
Strokes in CADASIL - Strokes or TIAs are the most common initial presentation of CADASIL. Ischemic strokes are the most frequent presentation of CADASIL with approximately 85% of symptomatic individuals developing transient ischemic attacks or stroke(s). The mean age of onset of ischemic episodes is approximately 46 years (range 30-70). A classic lacunar syndrome occurs in at least two-thirds of affected patients while hemispheric strokes are much less common. Notably, ischemic strokes typically occur in the absence of traditional cardiovascular risk factors. Recurrent silent strokes, with or without clinical strokes, often lead to cognitive decline and overt subcortical dementia.
# Treatment
No specific treatment is available. However, in some occasions, anti-coagulants can be used to slow down the disease and help prevent strokes. Given the propensity for cardiovascular and cerebrovascular complications, minimizing vascular risk factors and implementing therapy for primary or secondary prevention of stroke and myocardial infarction seems prudent. Stopping oral contraceptive pills is justified particularly in cases with migraine with aura. Aggressive treatment of hypercholesterolemia and hypertension is reasonable although the utility of statins and antihypertensive agents in the absence cardiovascular risk factors is unknown. Homocysteine levels are elevated in CADASIL and treatment with folic acid is reasonable. The role of anti-platelet agents and anticoagulation is unknown; anti-platelet therapy appears justifiable whereas anticoagulation may be inadvisable given the propensity for microhemorrhages. | CADASIL
CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy) is the most common form of hereditary stroke disorder, and is thought to be caused by mutations of the Notch 3 gene on chromosome 19.[1] The most common clinical manifestations are transient ischemic attacks or strokes, which usually occur between 40 and 50 years of age, although MRI is able to detect signs of the disease years prior to clinical manifestation of disease.[2]
# Pathophysiology
The underlying pathology of CADASIL is progressive degeneration of the smooth muscle cells in blood vessels. Mutations in the Notch 3 gene (on the short arm of chromosome 19) cause an abnormal accumulation of Notch 3 at the cytoplasmic membrane of vascular smooth-muscle cells both in cerebral and extracerebral vessels,[3] seen as granular osmiophilic deposits on electron microscopy.[4]
Interestingly, the Notch 3 gene is in the same locus as the gene for familial hemiplegic migraine.
# Clinical Features
CADASIL may start with attacks of migraine with aura or subcortical transient ischemic attacks or strokes, or mood disorders between 35 to 55 years of age. The disease progresses to subcortical dementia associated with pseudobulbar palsy and [[urinary incontinence].
# Diagnosis
MRI is the diagnostic modality of choice. Hypointensities on T1-weighted images and hyperintensities on T2-weighted images, usually multiple confluent white matter lesions of various sizes, are characteristic. These lesions are concentrated around the basal ganglia, periventricular white matter, and the pons, and are similar to those seen in Binswanger disease.[2][5] These white matter lesions are also seen in asymptomatic individuals with the mutated gene.[6]
The disease may also be diagnosed by screening for the mutated Notch 3 gene; however, this method is costly and laborious. Since CADASIL is a systemic arteriopathy, evidence of blood vessel damage is seen in small- and medium-sized arteries. It has therefore been suggested that skin biopsies could be used for diagnosis;[7] however, the lack of widespread availability of a monoclonal antibody required for diagnosis, limit the utility of this method.
# Clinical Course
Strokes in CADASIL - Strokes or TIAs are the most common initial presentation of CADASIL. Ischemic strokes are the most frequent presentation of CADASIL with approximately 85% of symptomatic individuals developing transient ischemic attacks or stroke(s). The mean age of onset of ischemic episodes is approximately 46 years (range 30-70). A classic lacunar syndrome occurs in at least two-thirds of affected patients while hemispheric strokes are much less common. Notably, ischemic strokes typically occur in the absence of traditional cardiovascular risk factors. Recurrent silent strokes, with or without clinical strokes, often lead to cognitive decline and overt subcortical dementia.
# Treatment
No specific treatment is available. However, in some occasions, anti-coagulants can be used to slow down the disease and help prevent strokes. Given the propensity for cardiovascular and cerebrovascular complications, minimizing vascular risk factors and implementing therapy for primary or secondary prevention of stroke and myocardial infarction seems prudent. Stopping oral contraceptive pills is justified particularly in cases with migraine with aura. Aggressive treatment of hypercholesterolemia and hypertension is reasonable although the utility of statins and antihypertensive agents in the absence cardiovascular risk factors is unknown. Homocysteine levels are elevated in CADASIL and treatment with folic acid is reasonable. The role of anti-platelet agents and anticoagulation is unknown; anti-platelet therapy appears justifiable whereas anticoagulation may be inadvisable given the propensity for microhemorrhages.
# External links
- The CADASIL Foundation A site devoted to promoting awareness, support and research for CADASIL among patients, their families and friends, and healthcare providers.
- The CADASIL support group A site devoted to raising awareness and forming a support group for CADASIL
- United Leukodystrophy Foundation: CADASIL | https://www.wikidoc.org/index.php/CADASIL | |
7469574868c4ee44c3197a9eb7c2d0530e0683a1 | wikidoc | CAPRIN2 | CAPRIN2
caprin family member 2, also known as CAPRIN2, is a human gene.
The protein encoded by this gene may be involved in the transitioning of erythroblasts from a highly proliferative state to a terminal phase of differentiation. High level expression of the encoded protein can lead to apoptosis. Several transcript variants encoding different isoforms have been found for this gene.
# Model organisms
Model organisms have been used in the study of CAPRIN2 function. A conditional knockout mouse line, called Caprin2tm1a(EUCOMM)Wtsi was generated as part of the International Knockout Mouse Consortium program — a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists — at the Wellcome Trust Sanger Institute.
Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion. Twenty two tests were carried out on mutant mice, however no significant abnormalities were observed. | CAPRIN2
caprin family member 2, also known as CAPRIN2, is a human gene.[1]
The protein encoded by this gene may be involved in the transitioning of erythroblasts from a highly proliferative state to a terminal phase of differentiation. High level expression of the encoded protein can lead to apoptosis. Several transcript variants encoding different isoforms have been found for this gene.[1]
# Model organisms
Model organisms have been used in the study of CAPRIN2 function. A conditional knockout mouse line, called Caprin2tm1a(EUCOMM)Wtsi[5][6] was generated as part of the International Knockout Mouse Consortium program — a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists — at the Wellcome Trust Sanger Institute.[7][8][9]
Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion.[3][10] Twenty two tests were carried out on mutant mice, however no significant abnormalities were observed.[3] | https://www.wikidoc.org/index.php/CAPRIN2 | |
a9bc32a58da7c19b1a62b0e09c6798ffdb25488d | wikidoc | CCDC113 | CCDC113
Coiled-coil domain-containing protein 113 also known as HSPC065, GC16Pof6842 and GC16P044152, is a protein that in humans is encoded by the CCDC113 gene. The human CCDC113 gene is located on chromosome 16q21 and encodes 5,304 base pairs of mRNA and 377 amino acids.
# Gene
CCDC113 is located on chromosome 16q21 and encodes two distinct isoforms with isoform 2 containing one less alternate in-frame exon compared to the full length protein, isoform 1. Isoform 1 is composed of 5304 base pairs of mRNA which form the 9 exons that make up the coding sequence.
CCDC113 Graphical Representation
CCDC113, located between nucleotides 58283840 and 58317740 on chromosome 16, is surrounded between antisense genes PRSS54 and CSNK2A2 and downstream from GINS3 and NDRG4 on the sense strand. PRSS54 is a trypsin-like serine protease which codes for the inactive serine protease 54 precursor. CSNK2A2 the casein kinase 2, alpha prime polypeptide contains a protein kinase domain and a catalytic domain. GINS3 is essential for the initiation of DNA replication and replisome progression in eukaryotes. NDRG4 a member of the N-myc downregulated gene family belonging to the alpha/beta hydrolase superfamily which encodes a cytoplasmic protein responsible for cell cycle progression and survival in primary astrocytes and may be involved in regulation of mitogenic signaling in vascular smooth muscle cells.
# Homology
## Paralogs
CCDC113 has one known paralog CCDC96 which has a query cover of 27% and a max identity value of 34%.
## Homologs
CCDC113 is highly conserved in all mammals and in organisms diverging back to Zebrafish, Danio rerio.
# Protein
The CCDC113 protein is composed of 377 amino acids which form a secondary structure composed primarily of alpha-helices. This protein contains a domain of unknown function DUF4201. There are many predicted post-translational modifications including phosphorylation, N-terminal acetylation, sumoylation, and N-glycosylation.
## Function
The function of CCDC113 is currently unknown.
## Expression
CCDC 113 is expressed at low levels in nearly all tissues of the body by RNA-seq including blood, lymph node, brain, heart, skeletal muscle, kidney, liver, colon, lung, thyroid, prostate, ovary, breast, adrenal gland, and adipocyte. The gene is also expressed in embryonic tissues and stem cells. There are high levels of expression in the cerebellum and in the testis and surrounding tissues.
## Interactions
Regulatory elements of CCDC113 include transcription factors ATF2, FOXD1, LCR-F1, C/EBPalpha, Max, AREB6, CBF-A, CBF(2), c-Myc, and HIF.
Interacting proteins found using two-hybrid screening techniques include GIT1; a G protein-coupled receptor kinase interacting ArfGAP, the cytoplasmic protein HAP1; Huntingtin-associated protein 1, IMMT, an inner mitochondrial membrane protein, and PFN2; Profilin 2- ubiquitous actin monomer binding protein.
## Clinical significance
Studies have linked expression of CCDC113 in cancerous tissues to mutations present in the coding sequence. Missense mutations at location 86 from Arginine to Tryptophan (R86Y) and at R180C are related to adenocarcinomas of the colon. Two point mutations have also been linked to adenocarcinomas of the rectum, a missense mutation of R361Q and a base pair point mutation c972t. Serous carcinoma of the ovaries has been related to a missense mutation S6F. | CCDC113
Coiled-coil domain-containing protein 113 also known as HSPC065, GC16Pof6842 and GC16P044152, is a protein that in humans is encoded by the CCDC113 gene. The human CCDC113 gene is located on chromosome 16q21 and encodes 5,304 base pairs of mRNA and 377 amino acids.[1][2][3]
# Gene
CCDC113 is located on chromosome 16q21 and encodes two distinct isoforms with isoform 2 containing one less alternate in-frame exon compared to the full length protein, isoform 1. Isoform 1 is composed of 5304 base pairs of mRNA which form the 9 exons that make up the coding sequence.[4]
CCDC113 Graphical Representation
CCDC113, located between nucleotides 58283840 and 58317740 on chromosome 16, is surrounded between antisense genes PRSS54 and CSNK2A2 and downstream from GINS3 and NDRG4 on the sense strand. PRSS54 is a trypsin-like serine protease which codes for the inactive serine protease 54 precursor.[6] CSNK2A2 the casein kinase 2, alpha prime polypeptide contains a protein kinase domain and a catalytic domain.[7] GINS3 is essential for the initiation of DNA replication and replisome progression in eukaryotes.[8] NDRG4 a member of the N-myc downregulated gene family belonging to the alpha/beta hydrolase superfamily which encodes a cytoplasmic protein responsible for cell cycle progression and survival in primary astrocytes and may be involved in regulation of mitogenic signaling in vascular smooth muscle cells.[9]
# Homology
## Paralogs
CCDC113 has one known paralog CCDC96 which has a query cover of 27% and a max identity value of 34%.[10]
## Homologs
CCDC113 is highly conserved in all mammals and in organisms diverging back to Zebrafish, Danio rerio.[10]
# Protein
The CCDC113 protein is composed of 377 amino acids which form a secondary structure composed primarily of alpha-helices.[4][11] This protein contains a domain of unknown function DUF4201. There are many predicted post-translational modifications including phosphorylation, N-terminal acetylation, sumoylation, and N-glycosylation.[12]
## Function
The function of CCDC113 is currently unknown.
## Expression
CCDC 113 is expressed at low levels in nearly all tissues of the body by RNA-seq including blood, lymph node, brain, heart, skeletal muscle, kidney, liver, colon, lung, thyroid, prostate, ovary, breast, adrenal gland, and adipocyte. The gene is also expressed in embryonic tissues and stem cells.[13] There are high levels of expression in the cerebellum and in the testis and surrounding tissues.[14]
## Interactions
Regulatory elements of CCDC113 include transcription factors ATF2, FOXD1, LCR-F1, C/EBPalpha, Max, AREB6, CBF-A, CBF(2), c-Myc, and HIF.[4]
Interacting proteins found using two-hybrid screening techniques include GIT1; a G protein-coupled receptor kinase interacting ArfGAP, the cytoplasmic protein HAP1; Huntingtin-associated protein 1,[15] IMMT, an inner mitochondrial membrane protein, and PFN2; Profilin 2- ubiquitous actin monomer binding protein.[4]
## Clinical significance
Studies have linked expression of CCDC113 in cancerous tissues to mutations present in the coding sequence. Missense mutations at location 86 from Arginine to Tryptophan (R86Y) and at R180C are related to adenocarcinomas of the colon. Two point mutations have also been linked to adenocarcinomas of the rectum, a missense mutation of R361Q and a base pair point mutation c972t. Serous carcinoma of the ovaries has been related to a missense mutation S6F.[16] | https://www.wikidoc.org/index.php/CCDC113 | |
0b680f7eb0af81b961a290e0f82e29e3be531527 | wikidoc | CCDC130 | CCDC130
Coiled-coil domain containing 130 is a protein that in humans is encoded by the CCDC130 gene. It is part of the U4/U5/U6 tri-snRNP in the U5 portion. This tri-snRNP comes together with other proteins to form complex B of the mature spliceosome. The mature protein is approximately 45 kilodaltons (kDa) and is extremely hydrophilic due to the abnormally high number of charged and polar amino acids. CCDC130 is a highly conserved protein, it has orthologous genes in some yeasts and plants that were found using nucleotide and protein versions of the basic local alignment search tool (BLAST) from the National Center for Biotechnology Information. GEO profiles for CCDC130 have shown that this protein is ubiquitously expressed, but the highest levels of expression are found in T-lymphocytes.
# Function
While the specific function of CCDC130 is still unknown, there have been several studies and research papers identifying it as a component of the U5 portion of the U4/U5/U6 tri-snRNP that helps form Complex B of the human spliceosome after coming together with Complex A. Complex B then undergoes more modifications and conformational changes before becoming a mature spliceosome. In one study, the conservation of spliceosomal components is discussed by comparing the human spliceosome with that of yeast. In this study, CCDC130 is categorized as a known splicing factor and its homolog in yeast is Yju2. This yeast protein is a splicing factor that helps form the complete, active spliceosome and promotes the first step of splicing, which involves cleavage at the 5' splice site of the first exon. Based on this information, it is likely that CCDC130 plays a similar role in the human spliceosome, but due to the higher complexity of the human spliceosome, this protein may perform other functions or a completely different function. Due to its high number of phosphorylation sites, it is likely that this protein is activated and recruited to the spliceosomal complex through phosphorylation or dephosphorylation (see Post-translational modifications). Since this gene is ubiquitously expressed and expressed 2.9 times higher than the average gene, it is clear that this protein plays an integral part in the proper function of the spliceosome.
# Gene
## Aliases
Coiled-coil domain containing 130 has several aliases, including CCDC130, SB115, LOC81576, and MGC10471.
## Locus
CCDC130 is located on the short arm of chromosome 19 in humans. The exact locus is 19p13.2. The entire gene spans from 13858753-13874106 on the + strand of chromosome 19. CCDC130 is bordered upstream by CACNA1A on the - strand, glatobu, smagly, and socho on the + strand, and downstream by MGC3207, C19orf53, ZSWIM4 on the + strand and joypaw, smeygly, floytobu, smawgly, and wycho on the - strand. Glatobu, smagly, socho, joypaw, smeygly, floytobu, smawgly, and wycho have only been verified by cDNA sequences in GenBank and have no information available about their function. There are also several small genes found within the CCDC130 sequence, with snugly, glytobu, stygly, and glartobu occurring on the + strand and chacho, zoycho, spogly, glotobu, glutobu, and sneygly occurring on the - strand. All of these small genes have extremely low levels of expression (under 3% of the expression of the average gene), with stygly having the highest expression at 2.8% of the average.
## Promoter
There were several predicted promoters found for CCDC130 using ElDorado from Genomatix, but the promoter that corresponds the closest to the protein sequence is 760 bases and spans from 13858094-13858853 on chromosome 19.
# Homology and evolution
## Paralogs
There is only one paralog identified for CCDC130, which is CCDC94, the only other known human member in the CWC16 family of proteins. The two have about 27% identity, most of which is located in the COG5134 domain and at the C-terminus. CCDC94 has three predicted serine phosphorylation sites at positions 213, 220, and 306 that line up with serines in CCDC130 in the multiple sequence alignment and a threonine phosphorylation site that lines up with a phosphorylated serine in CCDC130.
## Orthologs and homologs
CCDC130 is a highly conserved protein, with true orthologs present in primates, other mammals, amphibians, reptiles, fish, and even invertebrates, such as insects and marine invertebrates. Bird orthologs have not been found in nucleotide or protein BLASTs There have been homologous genes documented in yeasts and other fungi, as well as plants. It is unclear when the most distant homolog of CCDC130 arose, but it was well before the divergence of autotrophs and heterotrophs
## Conserved regions
CCDC130 has two conserved domains and a coiled-coil region. The first is the COG5134 domain which is found to be conserved in cucumbers and likely plays a role in the function of the protein because it is always the most highly conserved region in any multiple sequence alignment. It spans approximately the first 170 amino acids of the protein. The other domain is the DUF572 domain, which is a eukaryotic domain of unknown function that is shared by all of the orthologs and a majority of the more distant homologs. This domain doesn't have a defined range, as different sources have reported different lengths, some saying that it is the entire protein. The coiled-coil region is from 182-214 in the human protein and is rich in charged amino acids. The modified residues are also very well conserved.
# Protein
The most abundant variant of CCDC130 is encoded by the second longest open reading frame (ORF), corresponding to a 396 amino acid protein with a molecular weight of 44.8 kDa and an isoelectric point of 8.252. The CCDC130 protein is rich in charged amino acids and deficient in uncharged, non-polar amino acids. Mobyle @ Pasteur predicted CCDC130 to be extremely hydrophilic due to the large numbers of charged and polar amino acids, with no site scoring above zero on the hydrophobicity graph and some sites reaching as low as -6 (F180). There is a region in the coiled coil domain (182-214) in which 14 of 18 amino acids are charged. SAPS analysis predicted that this protein would be unstable. Due to its high hydrophilicity, this protein definitely does not contain transmembrane segments.
## Variation
There are 17 different mRNAS produced from the CCDC130 gene. 13 of these mRNAs come from alternative splicing, and the other four are unspliced. There have been four alternative promoters, five alternative polyadenylation sites, and four alternative last exons described. Two instances of intron retention have been described. 14 different proteins have been identified from the CCDC130 gene, all of which contain the DUF572 domain but only five seem to show the coiled-coil stretch. The other three mRNAs were very low quality and were not translated. It was also noted that this gene has the potential to encode several non-overlapping proteins. 45 SNPs have been documented for CCDC130 on NCBI: 29 missense mutations and 16 synonymous mutations that don't change the amino acid.
## Post-translational modifications
CCDC130 is a heavily phosphorylated protein, with 31 different phosphorylation sites predicted by NetPhos and 26 of those 31 being located in the C-terminal half of the protein. 17 of 22 serines, 4 of 6 threonines, and 2 of 3 tyrosines predicted had probability scores over .800, indicating a high likelihood that they are true phosphorylation sites. There were six sumoylation sites predicted, but only one of these sites (K177) had a probability score of higher than .500, at .640. The physiological function of sumoylation is still relatively mysterious, but this modification can add a substantial amount of molecular weight onto a protein (11 kDa). 13 glycation sites with probability scores over .500 were predicted, and 10 of the 13 glycated lysines occur in the N-terminal half of the protein. NetOGlyc predicted 11 possible O-glycosylationsites with probability scores over .500, with all 11 occurring in a 64 amino acid span running from T313 to T376. Several of these sites were predicted as both phosphorylation sites and O-glycosylation sites. CCDC130 was not predicted to be sulfated, acetylated, myristoylated, N-glycosylated, C-mannosylated, or undergo any GPI modification.
## Secondary structure
There is a long alpha helix sequence predicted in CCDC130 that spans from R121-A211 that was predicted by YASPIN. Other programs for secondary structure analysis, such as PELE, CHOFAS, and SABLE, also predicted alpha helices of varying lengths in this region. There were no consistent predictions for beta sheets in CCDC130.
# Interaction information
There are several proteins listed that interact with CCDC130, including EEF1A1, NINL, TRAF2, ZBTB16, ZNF165, and ZNF24. EEF1A1 is a eukaryotic elongation factor that is involved in the binding of aminoacyl-tRNA to the A-site of ribosomes during translation. NINL is a ninein-like protein that is involved in microtubule organization and has calcium ion binding activity. TRAF2, tumor necrosis factor (TNF) receptor associated factor 2, is part of some E3 ubiquitin ligase complexes and is involved in ubiquitinating proteins so they can get degraded by the proteasome. ZBTB16, zinc finger and BTB domain-containing protein 16, is also part of the E3 ubiquitin ligase complex and is most likely involved in substrate recognition. There is also an alternate form of CCDC130 where only 803 bases are transcribed instead of 1433 bases, but there is no additional information provided. ZNF165 and ZNF24 are both zinc finger proteins, which bind DNA and other proteins to regulate transcription. Below is a table of the interacting proteins for CCDC130 assembled by GeneCards. The interactions of CCDC130 with NINL, ZNF24, TRAF2, JUP, GATA5 have been verified by a two-hybrid screen according to STRING, so these interactions do occur. JUP is a plaque protein. GATA5 is a transcription factor that helps activate the promoter for lactase-phlorizin hydrolase. Interactions with CDA, DERA, CDC40, NAA25, DGCR14, NAA20, and PRPF19 have not been verified experimentally, but interactions between gene homologs have been documented in other species according to STRING so these interactions could potentially occur. ZBTB16, EEF1A1, and ZNF165 all have been verified by at least one two-hybrid screen according to MINT. NAT9 was described as a known interactant on I2D. In a study done at the University of the District of Columbia to characterize CCDC130, they have found that it is induced through insulin signaling, is targeted by three different kinases (GSK3, CK1, and CK2), and is a mitochondrial protein.5 The study also shows that CCDC130 can potentially be used as a biomarker for certain types of cancer due to its differential expression in cancer cells. The study specifically mentions that CCDC130 is downregulated in some types of colon cancer, which allowed more cancer cells to be untargeted by the apoptosis pathway.
# Expression
CCDC130 is a ubiquitously expressed protein, showing some expression level in all tissue and cell samples analyzed. The AceView profile for CCDC130 shows expression levels 2.9 times higher than the average protein. The level of expression varies greatly between tissues, but there is at least some level of expression in every sample. According to NCBI GEO profiles and BioGPS data, the fetal thyroid, adrenal cortex, uterus, prostate, testes, seminiferous tubule, heart, PB-CD4+ T cells, PB-CD8+ T cells, lymph node, lung, thymus, thyroid, leukemia chronic myelogenous K562, and leukemia lymphoblastic molt4 samples all had at expression levels above the 75th percentile for gene expression in at least one of two samples. Gene expression was lower than the 25th percentile in at least one of two samples for cerebellum peduncles, occipital lobe, pons, trigeminal ganglion, subthalamic nucleus, superior cervical ganglion (drastically different expression levels), dorsal root ganglion, fetal liver, uterus corpus, atrioventricular node, appendix, skeletal muscle, cardiac myocytes, tongue, and salivary gland. PB-CD8+ T cells had the highest relative CCDC130 expression and the tongue had the lowest relative expression. For more information about CCDC130 expression, see mouse brain expression data or human brain microarray data from Allen Brain Atlas or differential expression in GEO profiles from NCBI.
# Medical information
CCDC130 has shown to be differentially expressed in several cancers, including breast, colon, and pancreatic through microarray studies of cancer cells. It was shown to be down-regulated in colon cancers, suggesting that it could be a biomarker for cancers. There is still research being done on this topic to confirm its function as a cancer identifier. Many websites also say that it is involved in the cell's response to viral infection, but there is no specific information on this nor any elaboration. | CCDC130
Coiled-coil domain containing 130 is a protein that in humans is encoded by the CCDC130 gene. It is part of the U4/U5/U6 tri-snRNP in the U5 portion. This tri-snRNP comes together with other proteins to form complex B of the mature spliceosome. The mature protein is approximately 45 kilodaltons (kDa) and is extremely hydrophilic due to the abnormally high number of charged and polar amino acids.[1] CCDC130 is a highly conserved protein, it has orthologous genes in some yeasts and plants that were found using nucleotide and protein versions of the basic local alignment search tool (BLAST) from the National Center for Biotechnology Information.[2] GEO profiles for CCDC130 have shown that this protein is ubiquitously expressed, but the highest levels of expression are found in T-lymphocytes.[2]
# Function
While the specific function of CCDC130 is still unknown, there have been several studies and research papers identifying it as a component of the U5 portion of the U4/U5/U6 tri-snRNP that helps form Complex B of the human spliceosome after coming together with Complex A. Complex B then undergoes more modifications and conformational changes before becoming a mature spliceosome. In one study, the conservation of spliceosomal components is discussed by comparing the human spliceosome with that of yeast. In this study, CCDC130 is categorized as a known splicing factor and its homolog in yeast is Yju2.[3] This yeast protein is a splicing factor that helps form the complete, active spliceosome and promotes the first step of splicing, which involves cleavage at the 5' splice site of the first exon.[3] Based on this information, it is likely that CCDC130 plays a similar role in the human spliceosome, but due to the higher complexity of the human spliceosome, this protein may perform other functions or a completely different function. Due to its high number of phosphorylation sites, it is likely that this protein is activated and recruited to the spliceosomal complex through phosphorylation or dephosphorylation (see Post-translational modifications). Since this gene is ubiquitously expressed and expressed 2.9 times higher than the average gene, it is clear that this protein plays an integral part in the proper function of the spliceosome.[2]
# Gene
## Aliases
Coiled-coil domain containing 130 has several aliases, including CCDC130, SB115, LOC81576, and MGC10471.
## Locus
CCDC130 is located on the short arm of chromosome 19 in humans. The exact locus is 19p13.2. The entire gene spans from 13858753-13874106 on the + strand of chromosome 19.[2] CCDC130 is bordered upstream by CACNA1A on the - strand, glatobu, smagly, and socho on the + strand, and downstream by MGC3207, C19orf53, ZSWIM4 on the + strand and joypaw, smeygly, floytobu, smawgly, and wycho on the - strand.[2] Glatobu, smagly, socho, joypaw, smeygly, floytobu, smawgly, and wycho have only been verified by cDNA sequences in GenBank and have no information available about their function. There are also several small genes found within the CCDC130 sequence, with snugly, glytobu, stygly, and glartobu occurring on the + strand and chacho, zoycho, spogly, glotobu, glutobu, and sneygly occurring on the - strand.[2] All of these small genes have extremely low levels of expression (under 3% of the expression of the average gene), with stygly having the highest expression at 2.8% of the average.[2]
## Promoter
There were several predicted promoters found for CCDC130 using ElDorado from Genomatix, but the promoter that corresponds the closest to the protein sequence is 760 bases and spans from 13858094-13858853 on chromosome 19.[4]
# Homology and evolution
## Paralogs
There is only one paralog identified for CCDC130, which is CCDC94, the only other known human member in the CWC16 family of proteins. The two have about 27% identity, most of which is located in the COG5134 domain and at the C-terminus. CCDC94 has three predicted serine phosphorylation sites at positions 213, 220, and 306 that line up with serines in CCDC130 in the multiple sequence alignment and a threonine phosphorylation site that lines up with a phosphorylated serine in CCDC130.[1][5]
## Orthologs and homologs
CCDC130 is a highly conserved protein, with true orthologs present in primates, other mammals, amphibians, reptiles, fish, and even invertebrates, such as insects and marine invertebrates. Bird orthologs have not been found in nucleotide or protein BLASTs [2] There have been homologous genes documented in yeasts and other fungi, as well as plants. It is unclear when the most distant homolog of CCDC130 arose, but it was well before the divergence of autotrophs and heterotrophs
## Conserved regions
CCDC130 has two conserved domains and a coiled-coil region. The first is the COG5134 domain which is found to be conserved in cucumbers and likely plays a role in the function of the protein because it is always the most highly conserved region in any multiple sequence alignment.[1] It spans approximately the first 170 amino acids of the protein. The other domain is the DUF572 domain, which is a eukaryotic domain of unknown function that is shared by all of the orthologs and a majority of the more distant homologs. This domain doesn't have a defined range, as different sources have reported different lengths, some saying that it is the entire protein. The coiled-coil region is from 182-214 in the human protein and is rich in charged amino acids. The modified residues are also very well conserved.
# Protein
The most abundant variant of CCDC130 is encoded by the second longest open reading frame (ORF), corresponding to a 396 amino acid protein with a molecular weight of 44.8 kDa and an isoelectric point of 8.252.[1] The CCDC130 protein is rich in charged amino acids and deficient in uncharged, non-polar amino acids.[1] Mobyle @ Pasteur predicted CCDC130 to be extremely hydrophilic due to the large numbers of charged and polar amino acids, with no site scoring above zero on the hydrophobicity graph and some sites reaching as low as -6 (F180). There is a region in the coiled coil domain (182-214) in which 14 of 18 amino acids are charged. SAPS analysis predicted that this protein would be unstable.[1] Due to its high hydrophilicity, this protein definitely does not contain transmembrane segments.
## Variation
There are 17 different mRNAS produced from the CCDC130 gene. 13 of these mRNAs come from alternative splicing, and the other four are unspliced.[2] There have been four alternative promoters, five alternative polyadenylation sites, and four alternative last exons described.[2] Two instances of intron retention have been described. 14 different proteins have been identified from the CCDC130 gene, all of which contain the DUF572 domain but only five seem to show the coiled-coil stretch. The other three mRNAs were very low quality and were not translated. It was also noted that this gene has the potential to encode several non-overlapping proteins. 45 SNPs have been documented for CCDC130 on NCBI: 29 missense mutations and 16 synonymous mutations that don't change the amino acid.[2]
## Post-translational modifications
CCDC130 is a heavily phosphorylated protein, with 31 different phosphorylation sites predicted by NetPhos and 26 of those 31 being located in the C-terminal half of the protein.[5] 17 of 22 serines, 4 of 6 threonines, and 2 of 3 tyrosines predicted had probability scores over .800, indicating a high likelihood that they are true phosphorylation sites.[5] There were six sumoylation sites predicted, but only one of these sites (K177) had a probability score of higher than .500, at .640.[6] The physiological function of sumoylation is still relatively mysterious, but this modification can add a substantial amount of molecular weight onto a protein (11 kDa). 13 glycation sites with probability scores over .500 were predicted, and 10 of the 13 glycated lysines occur in the N-terminal half of the protein.[7] NetOGlyc predicted 11 possible O-glycosylationsites with probability scores over .500, with all 11 occurring in a 64 amino acid span running from T313 to T376.[8] Several of these sites were predicted as both phosphorylation sites and O-glycosylation sites. CCDC130 was not predicted to be sulfated,[9] acetylated,[10] myristoylated,[11] N-glycosylated,[12] C-mannosylated,[13] or undergo any GPI modification.[14]
## Secondary structure
There is a long alpha helix sequence predicted in CCDC130 that spans from R121-A211 that was predicted by YASPIN. Other programs for secondary structure analysis, such as PELE, CHOFAS, and SABLE, also predicted alpha helices of varying lengths in this region.[1][15] There were no consistent predictions for beta sheets in CCDC130.
# Interaction information
There are several proteins listed that interact with CCDC130, including EEF1A1, NINL, TRAF2, ZBTB16, ZNF165, and ZNF24. EEF1A1 is a eukaryotic elongation factor that is involved in the binding of aminoacyl-tRNA to the A-site of ribosomes during translation.[16] NINL is a ninein-like protein that is involved in microtubule organization and has calcium ion binding activity.[16] TRAF2, tumor necrosis factor (TNF) receptor associated factor 2, is part of some E3 ubiquitin ligase complexes and is involved in ubiquitinating proteins so they can get degraded by the proteasome.[16] ZBTB16, zinc finger and BTB domain-containing protein 16, is also part of the E3 ubiquitin ligase complex and is most likely involved in substrate recognition. There is also an alternate form of CCDC130 where only 803 bases are transcribed instead of 1433 bases, but there is no additional information provided.[17] ZNF165 and ZNF24 are both zinc finger proteins, which bind DNA and other proteins to regulate transcription. Below is a table of the interacting proteins for CCDC130 assembled by GeneCards.[17] The interactions of CCDC130 with NINL, ZNF24, TRAF2, JUP, GATA5 have been verified by a two-hybrid screen according to STRING, so these interactions do occur. JUP is a plaque protein. GATA5 is a transcription factor that helps activate the promoter for lactase-phlorizin hydrolase.[17] Interactions with CDA, DERA, CDC40, NAA25, DGCR14, NAA20, and PRPF19 have not been verified experimentally, but interactions between gene homologs have been documented in other species according to STRING so these interactions could potentially occur. ZBTB16, EEF1A1, and ZNF165 all have been verified by at least one two-hybrid screen according to MINT. NAT9 was described as a known interactant on I2D. In a study done at the University of the District of Columbia to characterize CCDC130, they have found that it is induced through insulin signaling, is targeted by three different kinases (GSK3, CK1, and CK2), and is a mitochondrial protein.5 The study also shows that CCDC130 can potentially be used as a biomarker for certain types of cancer due to its differential expression in cancer cells. The study specifically mentions that CCDC130 is downregulated in some types of colon cancer, which allowed more cancer cells to be untargeted by the apoptosis pathway.
# Expression
CCDC130 is a ubiquitously expressed protein, showing some expression level in all tissue and cell samples analyzed. The AceView profile for CCDC130 shows expression levels 2.9 times higher than the average protein.[2] The level of expression varies greatly between tissues, but there is at least some level of expression in every sample. According to NCBI GEO profiles and BioGPS data, the fetal thyroid, adrenal cortex, uterus, prostate, testes, seminiferous tubule, heart, PB-CD4+ T cells, PB-CD8+ T cells, lymph node, lung, thymus, thyroid, leukemia chronic myelogenous K562, and leukemia lymphoblastic molt4 samples all had at expression levels above the 75th percentile for gene expression in at least one of two samples. Gene expression was lower than the 25th percentile in at least one of two samples for cerebellum peduncles, occipital lobe, pons, trigeminal ganglion, subthalamic nucleus, superior cervical ganglion (drastically different expression levels), dorsal root ganglion, fetal liver, uterus corpus, atrioventricular node, appendix, skeletal muscle, cardiac myocytes, tongue, and salivary gland. PB-CD8+ T cells had the highest relative CCDC130 expression and the tongue had the lowest relative expression. For more information about CCDC130 expression, see mouse brain expression data or human brain microarray data from Allen Brain Atlas or differential expression in GEO profiles from NCBI.[2]
# Medical information
CCDC130 has shown to be differentially expressed in several cancers, including breast, colon, and pancreatic through microarray studies of cancer cells.[18] It was shown to be down-regulated in colon cancers, suggesting that it could be a biomarker for cancers. There is still research being done on this topic to confirm its function as a cancer identifier. Many websites also say that it is involved in the cell's response to viral infection, but there is no specific information on this nor any elaboration. | https://www.wikidoc.org/index.php/CCDC130 | |
3016350206602ced7548a5093e162d341bccc10e | wikidoc | CCDC137 | CCDC137
Coiled-coil domain containing 137 is a protein that in humans is encoded by the CCDC137 gene.
# Model organisms
Model organisms have been used in the study of CCDC137 function. A conditional knockout mouse line, called Ccdc137tm1a(KOMP)Wtsi was generated as part of the International Knockout Mouse Consortium program — a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists — at the Wellcome Trust Sanger Institute.
Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion. Twenty five tests were carried out on mutant mice and two significant abnormalities were observed. No homozygous mutant embryos were recorded during gestation and, in a separate study, no homozygous animals were observed at weaning. The remaining tests were carried out on adult heterozygous mutant animals, but no further abnormalities were seen. | CCDC137
Coiled-coil domain containing 137 is a protein that in humans is encoded by the CCDC137 gene.[1]
# Model organisms
Model organisms have been used in the study of CCDC137 function. A conditional knockout mouse line, called Ccdc137tm1a(KOMP)Wtsi[6][7] was generated as part of the International Knockout Mouse Consortium program — a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists — at the Wellcome Trust Sanger Institute.[8][9][10]
Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion.[4][11] Twenty five tests were carried out on mutant mice and two significant abnormalities were observed.[4] No homozygous mutant embryos were recorded during gestation and, in a separate study, no homozygous animals were observed at weaning. The remaining tests were carried out on adult heterozygous mutant animals, but no further abnormalities were seen.[4] | https://www.wikidoc.org/index.php/CCDC137 | |
cf3dacdeef09f79d49ab051d71f570be617f7668 | wikidoc | CCDC138 | CCDC138
Coiled-coil domain-containing protein 138, also known as CCDC138, is a human protein encoded by the CCDC138 gene. The exact function of CCDC138 is unknown.
# Gene
The CCDC138 gene can be found at the positive strand of chromosome 2.
## Locus
The CCDC138 gene is located at the long(q) arm of chromosome 2 at locus 12.13, or in short 2q12.3. It can be found at location 108,786,752-108,876,591. The DNA sequence is 89,840bp long.
## Common aliases
CCDC138 is the only established common alias.
# Homology and evolution
## Paralogs
No paralogs of CCDC138 have been identified.
## Orthologs
CCDC138 is conserved in various organisms as shown in the table below.
## Distant homologs
The most distant homolog detected or predicted is Trichoplax adhaerans. It has a conserved CCDC138 gene and has evolved 800 MYA before the human lineage.
## Homologous domains
Among the orthologs stated above, there are various homologous regions that are conserved shown in figures below.
Green colors shows completely conserved residues, yellow color shows identical residues, cyan color shows similar residues, white color shows different residues.
## Phylogeny
The observed phylogeny of the CCDC138 gene of the above mentioned orthologs recapitulates the evolutionary history.
The figure above shows the evolutionary relationship of CCDC138 in the orthologs.
# Protein
The CCDC138 protein is predated to have a molecular weight of 76.2Kda and an isoelectric point of 8.614. Compositional analysis shows that there is a low usage of the AGP grouping in CCDC138, and there are no positive, negative or mixed charge clusters. The protein has no ER retention motif in the C-terminus and no RNA binding motif. It has also been predicted to be a soluble nuclear protein with a leucine zipper pattern (PS00029) at position 205 onwards with a sequence LQKRERFLLEREQLLFRHENAL.
## Primary sequence and variants/isoforms
There are two isoforms of the CCDC138 protein. The primary isoform has 665 amino acids while the secondary isoform has 577 amino acids, and is missing 88 amino acids at the C-terminus.
Figure shows the pairwise sequence alignment comparing the primary isoform (Isoform 1) to the secondary isoform (Isoform 2).
## Domain and motifs
A domain of unknown function (DUF2317) on the protein at location 212 – 315 has been characterized in bacteria.
TMHMM and TMAP suggests that there are no predicted transmembrane domain. SOSUI further predicts that CCDC138 is a soluble protein with no transmembrane domain.
## Post-translational modifications
According to SUMOplot Analysis Program, there are 7 predicted sumoylation at lysine residues K7, K207, K336, K374, K383, K521, and K591.
NetPhos predicts that there are 44 phosphorylations sites, including 29 serine residues, 10 threonine residues, and 5 tyrosine residues.
There are no further post-translational modifications as predicted by NetNGlyc, NetOGlyc, SignalP, Sulfinator, and Myristoylator.
## Secondary structure
The CCDC138 protein contains multiple alpha helixes, beta sheets and coiled-coils as predicted by PELE, CHOFAS, and GOR4.
Yellow shows coiled-coil, blue shows alpha helix, and red shows beta sheet. The majority of the sequence are coiled-coils and alpha helixes.
## 3° and 4° structures
There are no predicted 3° and 4° Structures for the CCDC138 protein. However, there is a similar structure that has a 29% identity. The predicted structure is Chain A, crystal structure analysis of Clpb, a protein that encodes an ATP-dependent protease and chaperone. This protein has an aligned-length of 144 amino acids, and the alignment is located at the domain of unknown function of CCDC138.
# Expression
The gene is expressed at low levels in almost all human tissues, but higher levels have been seen in certain cancer tissues. CCDC138 is a soluble protein that is pre diced to localise in the nucleus of a cell.
## Promoter
The promoter region of CCDC138 is shown as figure below.
## Expression
Microarray-assessed tissue expression patterns through GEO profiles show that CCDC138 is expressed in moderate levels in various tissues including peripheral blood lymphocyte, fetal thymus, thymus, testis, ovary, feral brain, colon, mammary gland, and bone marrow.
## Transcript variants
There are two most significant alternative transcript variants for CCDC138 mRNA. The first variant as shown in the figure below has been found in lung, blood, and human embryonic stem cells. The second variant has been found in adenocarcinoma, prostate, lung, and primary lung epithelial cells.
First transcript shows the complete mRNA transcript. Second transcript is the first variant, while the thirst transcript is the second variant.
# Function and biochemistry
The exact function of CCDC138 is yet to be known.
# Interacting proteins
The CCDC138 protein has been found to interact with ubiquitin C, a protein involved in ubiquination and eventually protein degradation.
## Transcription factors that might bind to regulatory sequence
The table below shows some transcription factors that have been predicted by Genomatix that binds to the regulatory sequence of the CCDC138 gene.
# Clinical significance
CCDC138 has been identified as one of the many genes involved in initiating term labor in myometrium. | CCDC138
Coiled-coil domain-containing protein 138, also known as CCDC138, is a human protein encoded by the CCDC138 gene. The exact function of CCDC138 is unknown.
# Gene
The CCDC138 gene can be found at the positive strand of chromosome 2.[1]
## Locus
The CCDC138 gene is located at the long(q) arm of chromosome 2 at locus 12.13,[2] or in short 2q12.3. It can be found at location 108,786,752-108,876,591.[3] The DNA sequence is 89,840bp long.
## Common aliases
CCDC138 is the only established common alias.
# Homology and evolution
## Paralogs
No paralogs of CCDC138 have been identified.
## Orthologs
CCDC138 is conserved in various organisms as shown in the table below.
## Distant homologs
The most distant homolog detected or predicted is Trichoplax adhaerans. It has a conserved CCDC138 gene and has evolved 800 MYA before the human lineage.
## Homologous domains
Among the orthologs stated above, there are various homologous regions that are conserved shown in figures below.
Green colors shows completely conserved residues, yellow color shows identical residues, cyan color shows similar residues, white color shows different residues.
## Phylogeny
The observed phylogeny of the CCDC138 gene of the above mentioned orthologs recapitulates the evolutionary history.[5]
The figure above shows the evolutionary relationship of CCDC138 in the orthologs.
# Protein
The CCDC138 protein is predated to have a molecular weight of 76.2Kda[6] and an isoelectric point of 8.614.[7] Compositional analysis shows that there is a low usage of the AGP grouping in CCDC138, and there are no positive, negative or mixed charge clusters. The protein has no ER retention motif in the C-terminus and no RNA binding motif.[8] It has also been predicted to be a soluble nuclear protein with a leucine zipper pattern (PS00029) at position 205 onwards with a sequence LQKRERFLLEREQLLFRHENAL.[8]
## Primary sequence and variants/isoforms
There are two isoforms of the CCDC138 protein. The primary isoform has 665 amino acids[9] while the secondary isoform has 577 amino acids,[9] and is missing 88 amino acids at the C-terminus.
Figure shows the pairwise sequence alignment comparing the primary isoform (Isoform 1) to the secondary isoform (Isoform 2).
## Domain and motifs
A domain of unknown function (DUF2317) on the protein at location 212 – 315 has been characterized in bacteria.
TMHMM[10] and TMAP[11] suggests that there are no predicted transmembrane domain. SOSUI[12] further predicts that CCDC138 is a soluble protein with no transmembrane domain.
## Post-translational modifications
According to SUMOplot Analysis Program,[13] there are 7 predicted sumoylation at lysine residues K7, K207, K336, K374, K383, K521, and K591.
NetPhos[14] predicts that there are 44 phosphorylations sites, including 29 serine residues, 10 threonine residues, and 5 tyrosine residues.
There are no further post-translational modifications as predicted by NetNGlyc,[15] NetOGlyc,[16] SignalP,[17] Sulfinator,[18] and Myristoylator.[19]
## Secondary structure
The CCDC138 protein contains multiple alpha helixes, beta sheets and coiled-coils as predicted by PELE, CHOFAS, and GOR4.
Yellow shows coiled-coil, blue shows alpha helix, and red shows beta sheet. The majority of the sequence are coiled-coils and alpha helixes.
## 3° and 4° structures
There are no predicted 3° and 4° Structures for the CCDC138 protein. However, there is a similar structure that has a 29% identity.[20] The predicted structure is Chain A, crystal structure analysis of Clpb, a protein that encodes an ATP-dependent protease and chaperone. This protein has an aligned-length of 144 amino acids, and the alignment is located at the domain of unknown function of CCDC138.
# Expression
The gene is expressed at low levels in almost all human tissues, but higher levels have been seen in certain cancer tissues. CCDC138 is a soluble protein that is pre diced to localise in the nucleus of a cell.
## Promoter
The promoter region of CCDC138 is shown as figure below.
## Expression
Microarray-assessed tissue expression patterns through GEO profiles show that CCDC138 is expressed in moderate levels in various tissues including peripheral blood lymphocyte, fetal thymus, thymus, testis, ovary, feral brain, colon, mammary gland, and bone marrow.[21]
## Transcript variants
There are two most significant alternative transcript variants for CCDC138 mRNA. The first variant as shown in the figure below has been found in lung, blood, and human embryonic stem cells.[22] The second variant has been found in adenocarcinoma, prostate, lung, and primary lung epithelial cells.[23]
First transcript shows the complete mRNA transcript. Second transcript is the first variant, while the thirst transcript is the second variant.[24]
# Function and biochemistry
The exact function of CCDC138 is yet to be known.
# Interacting proteins
The CCDC138 protein has been found to interact with ubiquitin C,[25] a protein involved in ubiquination and eventually protein degradation.
## Transcription factors that might bind to regulatory sequence
The table below shows some transcription factors that have been predicted by Genomatix that binds to the regulatory sequence of the CCDC138 gene.[26]
# Clinical significance
CCDC138 has been identified as one of the many genes involved in initiating term labor in myometrium.[27] | https://www.wikidoc.org/index.php/CCDC138 | |
f5f737bd34980d1a33e2954e04fca582010ef277 | wikidoc | CCDC176 | CCDC176
Basal body-orientation factor 1 (BBOF1) is a protein that in humans is encoded by the gene CCDC176, which is located on the plus strand of chromosome 14 at 14q24.3. CCDC176 is neighbored by ALDH6A1 and ENTPD5 at the same locus.
The mRNA is 3123 base pairs long and has 12 exons, the protein is 529 amino acids long and has a molecular weight of 61987 Da and a predicted isoelectric point of 9.07 in humans.
# Homology and evolution
CCDC176 has no known paralogs and is orthologous in primates, mammals, birds, reptiles, amphibians, fish, all the way back to invertebrates, a fungi parasite and a proteobacteria. The domain found to be homologous is the DUF4515, a domain of unknown function.
# Protein function and characteristics
This basal body protein has been shown in multiciliated cells to align and maintain cilia orientation in response to flow. This protein may also act by mediating a maturation step that stabilizes and aligns cilia orientation.
No other genes or proteins have been found that encode basal body orientation factors. A similar set of genes, tubulin tyrosine ligase-like genes 3 and 6, has been found in zebrafish that maintain cilia structure and motility. These genes belong to the TTL (tubulin tyrosine ligase) family.
BBOF1 has two coiled coil domains, one that is 117 amino acids in length at the position 85-201 and the second is 91 amino acids in length at the position 271-361. There is also a region of interest located at the position 77-270 and is named DUF4515, a domain of unknown function belonging to the family of pfam14988.
There are three predicted protein-protein interactions concerning CCDC176. The most prevalent and most likely interaction is with LIG4, a human gene that encodes the protein DNA Ligase IV. Two experiments in a publication of 1030 unique reactions support the LIG4-CCDC176 interaction. The second and third predicted interactions are NRF1 and HYLS1.
The predicted secondary structure of BBOF1 in humans is as follows: 87.1% alpha helix, 63.9% beta sheet, and 15.7% beta turn.
# Expression, research, and clinical significance
CCDC176 has known expression in the human testis, cerebellum, and lung tissues.
There are six articles of research related to the gene CCDC176, with four out of six being large-scale sequencing, one article not naming the gene or protein, and one article with only the abstract available. This last article, Global, in vivo, and site-specific phosphorylation dynamics in signaling networks, is the only article that directly mentions the protein of interest and it does so only once. This study detected 6,600 phosphorylation sites on 2,244 proteins.
Expression data from different health states in humans predicts high expression of CCDC176 in glioma.
The interaction data concerning CCDC176 and LIG4 came from a publication studying protein-protein interaction involved with the DNA damage response network in association with cancer | CCDC176
Basal body-orientation factor 1 (BBOF1) is a protein that in humans is encoded by the gene CCDC176, which is located on the plus strand of chromosome 14 at 14q24.3.[1] CCDC176 is neighbored by ALDH6A1 and ENTPD5 at the same locus.[2]
The mRNA is 3123 base pairs long and has 12 exons, the protein is 529 amino acids long and has a molecular weight of 61987 Da and a predicted isoelectric point of 9.07 in humans.[3]
# Homology and evolution
CCDC176 has no known paralogs and is orthologous in primates, mammals, birds, reptiles, amphibians, fish, all the way back to invertebrates, a fungi parasite and a proteobacteria. The domain found to be homologous is the DUF4515, a domain of unknown function.
# Protein function and characteristics
This basal body protein has been shown in multiciliated cells to align and maintain cilia orientation in response to flow. This protein may also act by mediating a maturation step that stabilizes and aligns cilia orientation.[4]
No other genes or proteins have been found that encode basal body orientation factors. A similar set of genes, tubulin tyrosine ligase-like genes 3 and 6, has been found in zebrafish that maintain cilia structure and motility. These genes belong to the TTL (tubulin tyrosine ligase) family.[5]
BBOF1 has two coiled coil domains, one that is 117 amino acids in length at the position 85-201 and the second is 91 amino acids in length at the position 271-361.[6] There is also a region of interest located at the position 77-270 and is named DUF4515, a domain of unknown function belonging to the family of pfam14988.[7]
There are three predicted protein-protein interactions concerning CCDC176. The most prevalent and most likely interaction is with LIG4, a human gene that encodes the protein DNA Ligase IV.[8] Two experiments in a publication of 1030 unique reactions support the LIG4-CCDC176 interaction.[9] The second and third predicted interactions are NRF1[10] and HYLS1.[11]
The predicted secondary structure of BBOF1 in humans is as follows: 87.1% alpha helix, 63.9% beta sheet, and 15.7% beta turn.[12]
# Expression, research, and clinical significance
CCDC176 has known expression in the human testis, cerebellum, and lung tissues.[13]
There are six articles of research related to the gene CCDC176, with four out of six being large-scale sequencing, one article not naming the gene or protein, and one article with only the abstract available. This last article, Global, in vivo, and site-specific phosphorylation dynamics in signaling networks, is the only article that directly mentions the protein of interest and it does so only once. This study detected 6,600 phosphorylation sites on 2,244 proteins.[14]
Expression data from different health states in humans predicts high expression of CCDC176 in glioma.[15]
The interaction data concerning CCDC176 and LIG4 came from a publication studying protein-protein interaction involved with the DNA damage response network in association with cancer[16] | https://www.wikidoc.org/index.php/CCDC176 | |
b34ff58324ab338dc2ef8c1b327493b34a70fced | wikidoc | CCDC181 | CCDC181
Coiled-coil domain-containing protein 181 (CCDC181) is a protein that in human is encoded by C1orf114, which is located at the Chromosome 1 at 1q24.2. The accession is Q5T1D7. Researches have recently revealed that CCDC 181 is a microtubule-binding protein that interacts with murine Hook1 in haploid male germ cells and localizes to the sperm tail and motile cilia. The disruption of Hook1 may lead to inappropriate function of spermatogenesis. The dysfunction may be related to the abnormal head shape of sperm or distinctive structural changes in flagella in sperm, and could be possible end up in male infertility. An increased rate of my gene has found in the haploid phase of male cell during meiosis, thus it is believed to relate to sperm cell and aid in spermatogenesis.
# Expression
It is discovered that a significant high expression of CCDC 181 found on human testis, which is a male reproductive gland. This is related to the study of its encoded protein-CCDC181, which relates to human infertility when in low expression. Also, high expression of protein is found in the olfactory area and cortical subplate. Researchers have studied the expression of CCDC 181 under different conditions. One of the outstanding findings is that under the coexistence of Rho GTP dissociation inhibitor, the expression of CCDC 181 is depressed. Rho GTP dissociation inhibitor has a phenomenal effect on bladder cancer cells, so studies have suggested that CCDC 181 might also be related to bladder cancer.
# Homology
Orthologs have been found mainly in eukaryotes, including mammals, birds, reptiles, amphibians and fishes, with the highest identity on the mammalian species.
- ↑ Jump up to: 1.0 1.1 1.2 "Homo sapiens coiled-coil domain containing 181 (CCDC181), transcript v - Nucleotide - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2018-05-01..mw-parser-output cite.citation{font-style:inherit}.mw-parser-output q{quotes:"\"""\"""'""'"}.mw-parser-output code.cs1-code{color:inherit;background:inherit;border:inherit;padding:inherit}.mw-parser-output .cs1-lock-free a{background:url("")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-limited a,.mw-parser-output .cs1-lock-registration a{background:url("")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-subscription a{background:url("")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration{color:#555}.mw-parser-output .cs1-subscription span,.mw-parser-output .cs1-registration span{border-bottom:1px dotted;cursor:help}.mw-parser-output .cs1-hidden-error{display:none;font-size:100%}.mw-parser-output .cs1-visible-error{display:none;font-size:100%}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration,.mw-parser-output .cs1-format{font-size:95%}.mw-parser-output .cs1-kern-left,.mw-parser-output .cs1-kern-wl-left{padding-left:0.2em}.mw-parser-output .cs1-kern-right,.mw-parser-output .cs1-kern-wl-right{padding-right:0.2em}
- ↑ Schwarz T, Prieler B, Schmid JA, Grzmil P, Neesen J (May 2017). "Ccdc181 is a microtubule-binding protein that interacts with Hook1 in haploid male germ cells and localizes to the sperm tail and motile cilia". European Journal of Cell Biology. 96 (3): 276–288. doi:10.1016/j.ejcb.2017.02.003. PMC 5496667. PMID 28283191. | CCDC181
Coiled-coil domain-containing protein 181 (CCDC181) is a protein that in human is encoded by C1orf114,[1] which is located at the Chromosome 1 at 1q24.2.[1] The accession is Q5T1D7.[1] Researches have recently revealed that CCDC 181 is a microtubule-binding protein that interacts with murine Hook1 in haploid male germ cells and localizes to the sperm tail and motile cilia.[2] The disruption of Hook1 may lead to inappropriate function of spermatogenesis. The dysfunction may be related to the abnormal head shape of sperm or distinctive structural changes in flagella in sperm, and could be possible end up in male infertility. An increased rate of my gene has found in the haploid phase of male cell during meiosis, thus it is believed to relate to sperm cell and aid in spermatogenesis.
# Expression
It is discovered that a significant high expression of CCDC 181 found on human testis, which is a male reproductive gland. This is related to the study of its encoded protein-CCDC181, which relates to human infertility when in low expression. Also, high expression of protein is found in the olfactory area and cortical subplate. Researchers have studied the expression of CCDC 181 under different conditions. One of the outstanding findings is that under the coexistence of Rho GTP dissociation inhibitor, the expression of CCDC 181 is depressed. Rho GTP dissociation inhibitor has a phenomenal effect on bladder cancer cells, so studies have suggested that CCDC 181 might also be related to bladder cancer.
# Homology
Orthologs have been found mainly in eukaryotes, including mammals, birds, reptiles, amphibians and fishes, with the highest identity on the mammalian species.
- ↑ Jump up to: 1.0 1.1 1.2 "Homo sapiens coiled-coil domain containing 181 (CCDC181), transcript v - Nucleotide - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2018-05-01..mw-parser-output cite.citation{font-style:inherit}.mw-parser-output q{quotes:"\"""\"""'""'"}.mw-parser-output code.cs1-code{color:inherit;background:inherit;border:inherit;padding:inherit}.mw-parser-output .cs1-lock-free a{background:url("https://upload.wikimedia.org/wikipedia/commons/thumb/6/65/Lock-green.svg/9px-Lock-green.svg.png")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-limited a,.mw-parser-output .cs1-lock-registration a{background:url("https://upload.wikimedia.org/wikipedia/commons/thumb/d/d6/Lock-gray-alt-2.svg/9px-Lock-gray-alt-2.svg.png")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-subscription a{background:url("https://upload.wikimedia.org/wikipedia/commons/thumb/a/aa/Lock-red-alt-2.svg/9px-Lock-red-alt-2.svg.png")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration{color:#555}.mw-parser-output .cs1-subscription span,.mw-parser-output .cs1-registration span{border-bottom:1px dotted;cursor:help}.mw-parser-output .cs1-hidden-error{display:none;font-size:100%}.mw-parser-output .cs1-visible-error{display:none;font-size:100%}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration,.mw-parser-output .cs1-format{font-size:95%}.mw-parser-output .cs1-kern-left,.mw-parser-output .cs1-kern-wl-left{padding-left:0.2em}.mw-parser-output .cs1-kern-right,.mw-parser-output .cs1-kern-wl-right{padding-right:0.2em}
- ↑ Schwarz T, Prieler B, Schmid JA, Grzmil P, Neesen J (May 2017). "Ccdc181 is a microtubule-binding protein that interacts with Hook1 in haploid male germ cells and localizes to the sperm tail and motile cilia". European Journal of Cell Biology. 96 (3): 276–288. doi:10.1016/j.ejcb.2017.02.003. PMC 5496667. PMID 28283191. | https://www.wikidoc.org/index.php/CCDC181 |
Subsets and Splits
No community queries yet
The top public SQL queries from the community will appear here once available.