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47543f143eb625491eee5b10140e8a5f2c426694 | wikidoc | ATP5I | ATP5I
ATP synthase subunit e, mitochondrial is an enzyme that in humans is encoded by the ATP5ME gene.
Mitochondrial ATP synthase catalyzes ATP synthesis, utilizing an electrochemical gradient of protons across the inner membrane during oxidative phosphorylation. It is composed of two linked multi-subunit complexes: the soluble catalytic core, F1, and the membrane-spanning component, Fo, which comprises the proton channel. The F1 complex consists of 5 different subunits (alpha, beta, gamma, delta, and epsilon) assembled in a ratio of 3 alpha, 3 beta, and a single representative of the other 3. The Fo seems to have nine subunits (a, b, c, d, e, f, g, F6 and 8). This gene encodes the e subunit of the Fo complex.
In yeast, the FO complex E subunit appears to play an important role in supporting F-ATPase dimerisation. This subunit is anchored to the inner mitochondrial membrane via its N-terminal region, which is involved in stabilising subunits G and K of the FO complex. The C-terminal region of subunit E is hydrophilic, protruding into the intermembrane space where it can also help stabilise the F-ATPase dimer complex. | ATP5I
ATP synthase subunit e, mitochondrial is an enzyme that in humans is encoded by the ATP5ME gene.[1][2]
Mitochondrial ATP synthase catalyzes ATP synthesis, utilizing an electrochemical gradient of protons across the inner membrane during oxidative phosphorylation. It is composed of two linked multi-subunit complexes: the soluble catalytic core, F1, and the membrane-spanning component, Fo, which comprises the proton channel. The F1 complex consists of 5 different subunits (alpha, beta, gamma, delta, and epsilon) assembled in a ratio of 3 alpha, 3 beta, and a single representative of the other 3. The Fo seems to have nine subunits (a, b, c, d, e, f, g, F6 and 8). This gene encodes the e subunit of the Fo complex.[2]
In yeast, the FO complex E subunit appears to play an important role in supporting F-ATPase dimerisation. This subunit is anchored to the inner mitochondrial membrane via its N-terminal region, which is involved in stabilising subunits G and K of the FO complex. The C-terminal region of subunit E is hydrophilic, protruding into the intermembrane space where it can also help stabilise the F-ATPase dimer complex.[3] | https://www.wikidoc.org/index.php/ATP5I | |
f6f48a375b09e90205197fdabdbacb569739ffc9 | wikidoc | ATP5J | ATP5J
ATP synthase-coupling factor 6, mitochondrial is an enzyme that in humans is encoded by the ATP5PF gene.
# Function
Mitochondrial ATP synthase catalyzes ATP synthesis, utilizing an electrochemical gradient of protons across the inner membrane during oxidative phosphorylation. It is composed of two linked multi-subunit complexes: the soluble catalytic core, F1, and the membrane-spanning component, F0, which comprises the proton channel. The F1 complex consists of 5 different subunits (alpha, beta, gamma, delta, and epsilon) assembled in a ratio of 3 alpha, 3 beta, and a single representative of the other 3. The Fo seems to have nine subunits (a, b, c, d, e, f, g, F6 and 8). This gene encodes the F6 subunit of the F0 complex, required for F1 and Fo interactions. Alternatively spliced transcript variants encoding different isoforms have been identified for this gene.
The F6 subunit is part of the peripheral stalk that links the F1 and FO complexes together, and which acts as a stator to prevent certain subunits from rotating with the central rotary element. The peripheral stalk differs in subunit composition between mitochondrial, chloroplast and bacterial F-ATPases. In mitochondria, the peripheral stalk is composed of one copy each of subunits OSCP (oligomycin sensitivity conferral protein), F6, B and D. There is no homologue of subunit F6 in bacterial or chloroplast F-ATPase, whose peripheral stalks are composed of one copy of the delta subunit (homologous to OSCP), and two copies of subunit B in bacteria, or one copy each of subunits B and B' in chloroplasts and photosynthetic bacteria. | ATP5J
ATP synthase-coupling factor 6, mitochondrial is an enzyme that in humans is encoded by the ATP5PF gene.[1][2][3]
# Function
Mitochondrial ATP synthase catalyzes ATP synthesis, utilizing an electrochemical gradient of protons across the inner membrane during oxidative phosphorylation. It is composed of two linked multi-subunit complexes: the soluble catalytic core, F1, and the membrane-spanning component, F0, which comprises the proton channel. The F1 complex consists of 5 different subunits (alpha, beta, gamma, delta, and epsilon) assembled in a ratio of 3 alpha, 3 beta, and a single representative of the other 3. The Fo seems to have nine subunits (a, b, c, d, e, f, g, F6 and 8). This gene encodes the F6 subunit of the F0 complex, required for F1 and Fo interactions. Alternatively spliced transcript variants encoding different isoforms have been identified for this gene.[3]
The F6 subunit is part of the peripheral stalk that links the F1 and FO complexes together, and which acts as a stator to prevent certain subunits from rotating with the central rotary element. The peripheral stalk differs in subunit composition between mitochondrial, chloroplast and bacterial F-ATPases. In mitochondria, the peripheral stalk is composed of one copy each of subunits OSCP (oligomycin sensitivity conferral protein), F6, B and D.[4] There is no homologue of subunit F6 in bacterial or chloroplast F-ATPase, whose peripheral stalks are composed of one copy of the delta subunit (homologous to OSCP), and two copies of subunit B in bacteria, or one copy each of subunits B and B' in chloroplasts and photosynthetic bacteria. | https://www.wikidoc.org/index.php/ATP5J | |
7e4d5d37a719d9fae92f060facabdc43781ea2c2 | wikidoc | ATP5L | ATP5L
ATP synthase subunit g, mitochondrial is an enzyme that in humans is encoded by the ATP5MG gene.
Mitochondrial ATP synthase catalyzes ATP synthesis, utilizing an electrochemical gradient of protons across the inner membrane during oxidative phosphorylation. It is composed of two linked multi-subunit complexes: the soluble catalytic core, F1, and the membrane-spanning component, Fo, which comprises the proton channel. The F1 complex consists of 5 different subunits (alpha, beta, gamma, delta, and epsilon) assembled in a ratio of 3 alpha, 3 beta, and a single representative of the other 3. The Fo seems to have nine subunits (a, b, c, d, e, f, g, F6 and 8). This gene encodes the g subunit of the F0 complex.
The function of subunit G is currently unknown. There is no counterpart in chloroplast or bacterial F-ATPases identified so far. | ATP5L
ATP synthase subunit g, mitochondrial is an enzyme that in humans is encoded by the ATP5MG gene.[1][2][3]
Mitochondrial ATP synthase catalyzes ATP synthesis, utilizing an electrochemical gradient of protons across the inner membrane during oxidative phosphorylation. It is composed of two linked multi-subunit complexes: the soluble catalytic core, F1, and the membrane-spanning component, Fo, which comprises the proton channel. The F1 complex consists of 5 different subunits (alpha, beta, gamma, delta, and epsilon) assembled in a ratio of 3 alpha, 3 beta, and a single representative of the other 3. The Fo seems to have nine subunits (a, b, c, d, e, f, g, F6 and 8). This gene encodes the g subunit of the F0 complex.[3]
The function of subunit G is currently unknown. There is no counterpart in chloroplast or bacterial F-ATPases identified so far.[4] | https://www.wikidoc.org/index.php/ATP5L | |
24d384e70a9ddeb4db62be25960bfef3abc56e7b | wikidoc | ATP7A | ATP7A
ATP7A, also known as Menkes' protein (MNK), is a copper-transporting P-type ATPase which uses the energy arising from ATP hydrolysis to transport Cu(I) across cell membranes. The ATP7A protein is a transmembrane protein and is expressed in the intestine and all tissues except liver. In the intestine, ATP7A regulates Cu(I) absorption in the human body by transporting Cu(I) from the small intestine into the blood. In other tissues, ATP7A shuttles between the Golgi apparatus and the cell membrane to maintain proper Cu(I) concentrations (since there is no free Cu(I) in the cell, Cu(I) ions are all tightly bound) in the cell and provides certain enzymes with Cu(I) (e.g. peptidyl-α-monooxygenase, tyrosinase, and lysyl oxidase). The X-linked, inherited, lethal genetic disorder of the ATP7A gene causes Menkes disease, a copper deficiency resulting in early childhood death.
# Gene
The ATP7A gene is located on the long (q) arm of the X chromosome at band Xq21.1. The encoded ATP7A protein has 1,500 amino acids. Mutations/additions/deletions of this gene often cause copper deficiency, which leads to progressive neurodegeneration and death in children.
# Structure
ATP7A is a transmembrane protein with the N- and C-termini both oriented towards the cytosol (see picture). It is highly homologous to protein ATP7B. ATP7A contains three major functional domains:
- Eight transmembrane segments that form a channel and allow for Cu(I) to pass through the membrane;
- An ATP-binding domain;
- A large N-terminal cytosolic domain that contains six repeated Cu(I)-binding sites, each containing a GMTCXXC motif.
Many motifs in the ATP7A structure are conserved:
- The TGEA motif lies in the loop on the cytosolic side between transmembrane segments 4 and 5 and is involved in energy transfer.
- The CPC motif located in transmembrane segment 6 is common for all heavy metal transporting ATPases.
Between transmembrane segments 6 and 7 is a large cytoplasmic loop, where three motifs are located: DKTG, SEHPL, and GDGXND.
- The DKTG motif is essential for the proper function of the ATPase. The aspartic acid (D) residue is phosphorylated during the transport cycles.
- The SEHPL motif only exists in heavy metal transporting P-type ATPases. Without the histidine (H) residue ATP7A may not function properly.
- The GDGXND motif near transmembrane segment 7 is thought to contain mainly α-helices and serves as a structural support.
The six Cu(I)-binding sites at the N-terminal bind one Cu(I) each. This binding site is not specific for Cu(I) and can bind various transition metal ions. Cd(II), Au(III) and Hg(II) bind to the binding site more tightly than does Zn(II), whereas Mn(II) and Ni(II) have lower affinities relative to Zn(II). In the case of Cu(I), a possible cooperative-binding mechanism is observed. When the Cu(I) concentration is low, Cu(I) has a lower affinity for ATP7A compared to Zn(II); as the Cu(I) concentration increases, a dramatic increasing affinity of Cu(I) for the protein is observed.
# Conformational change
The two cysteine (C) residues in each Cu(I)-binding site are coordinated to Cu(I) with a S-Cu(I)-S angle between 120 and 180° and a Cu-S distance of 2.16 Å. Experimental results from a homologous protein ATP7B suggests that reducing reagents are involved, and upon Cu(I) binding the disulfide bonding between the cysteine residues is broken as cysteine starts to bind to Cu(I), leading to a series of conformational changes at the N-terminal of the protein, and possibly activating the Cu(I)-transporting activity of other cytosolic loops.
Of the six copper(I)-binding sites, two are considered enough for the function of Cu(I) transport. The reason why there are six binding sites remains not fully understood. However, some scientists have proposed that the other four sites may serve as a Cu(I) concentration detector.
# Transport mechanism
ATP7A belongs to a transporter family called P-type ATPases, which catalyze auto-phosphorylation of a key conserved aspartic acid (D) residue within the enzyme. The first step is ATP binding to the ATP-binding domain and Cu(I) binding to the transmembrane region. Then ATP7A is phosphorylated at the key aspartic acid (D) residue in the highly conserved DKTG motif, accompanied by Cu(I) release. A subsequent dephosphorylation of the intermediate finishes the catalytic cycle. Within each cycle, ATP7A interconverts between at least two different conformations, E1 and E2. In the E1 state, Cu(I) is tightly bound to the binding sites on the cytoplasmic side; in the E2 state, the affinity of ATP7A for Cu(I) decreases and Cu(I) is released on the extracellular side.
# Function
ATP7A is important for regulating copper Cu(I) in mammals. This protein is found in most tissues, but it is not expressed in the liver. In the small intestine, the ATP7A protein helps control the absorption of Cu(I) from food. After Cu(I) ions are absorbed into enterocytes, ATP7A is required to transfer them across the basolateral membrane into the circulation.
In other organs and tissues, the ATP7A protein has a dual role and shuttles between two locations within the cell. The protein normally resides in a cell structure called the Golgi apparatus, which modifies and transports newly produced enzymes and other proteins. Here, ATP7A supplies Cu(I) to certain enzymes (e.g. peptidyl-α-monooxygenase, tyrosinase, and lysyl oxidase) that are critical for the structures and functions of brain, bone, skin, hair, connective tissue, and the nervous system. If Cu(I) levels in the cell environment are elevated, however, ATP7A moves to the cell membrane and eliminates excess Cu(I) from the cell.
The functions of ATP7A in some tissues of the human body are as follows:
# Interactions
ATP7A has been shown to interact with ATOX1 and GLRX. Antioxidant 1 copper chaperone (ATOX1) is required to maintain Cu(I) copper homeostasis in the cell. It can bind and transport cytosolic Cu(I) to ATP7A in the trans-Golgi-network. Glutaredoxin-1 (GRX1) has is also essential for ATP7A function. It promotes Cu(I) binding for subsequent transport by catalyzing the reduction of disulfide bridges. It may also catalyze de-glutathionylation reaction of the C (cysteine) residues within the six Cu(I)-binding motifs GMTCXXC.
# Clinical significance
Menkes disease is caused by mutations in the ATP7A gene. Researchers have identified different ATP7A mutations that cause Menkes disease and occipital horn syndrome (OHS), the milder form of Menkes disease. Many of these mutations delete part of the gene and are predicted to produce a shortened ATP7A protein that is unable to transport Cu(I). Other mutations insert additional DNA base pairs or use the wrong base pairs, which leads to ATP7A proteins that do not function properly.
The altered proteins that result from ATP7A mutations impair the absorption of copper from food, fail to supply copper to certain enzymes, or get stuck in the cell membrane, unable to shuttle back and forth from the Golgi. As a result of the disrupted activity of the ATP7A protein, copper is poorly distributed to cells in the body. Copper accumulates in some tissues, such as the small intestine and kidneys, while the brain and other tissues have unusually low levels. The decreased supply of copper can reduce the activity of numerous copper-containing enzymes that are necessary for the structure and function of bone, skin, hair, blood vessels, and the nervous system. Copper is also critical for the propagation of prion proteins, and mice with mutations in Atp7a have a delayed onset of prion disease.
# Inhibition
A proton pump inhibitor, Omeprazole, has been shown to block ATP7A, in addition to its more established role of blocking ATP4A. | ATP7A
ATP7A, also known as Menkes' protein (MNK), is a copper-transporting P-type ATPase which uses the energy arising from ATP hydrolysis to transport Cu(I) across cell membranes. The ATP7A protein is a transmembrane protein and is expressed in the intestine and all tissues except liver. In the intestine, ATP7A regulates Cu(I) absorption in the human body by transporting Cu(I) from the small intestine into the blood. In other tissues, ATP7A shuttles between the Golgi apparatus and the cell membrane to maintain proper Cu(I) concentrations (since there is no free Cu(I) in the cell, Cu(I) ions are all tightly bound) in the cell and provides certain enzymes with Cu(I) (e.g. peptidyl-α-monooxygenase, tyrosinase, and lysyl oxidase). The X-linked, inherited, lethal genetic disorder of the ATP7A gene causes Menkes disease, a copper deficiency resulting in early childhood death.[1]
# Gene
The ATP7A gene is located on the long (q) arm of the X chromosome at band Xq21.1. The encoded ATP7A protein has 1,500 amino acids.[2] Mutations/additions/deletions of this gene often cause copper deficiency, which leads to progressive neurodegeneration and death in children.[3]
# Structure
ATP7A is a transmembrane protein with the N- and C-termini both oriented towards the cytosol (see picture). It is highly homologous to protein ATP7B. ATP7A contains three major functional domains:[4][5][6][7]
- Eight transmembrane segments that form a channel and allow for Cu(I) to pass through the membrane;
- An ATP-binding domain;
- A large N-terminal cytosolic domain that contains six repeated Cu(I)-binding sites, each containing a GMTCXXC motif.
Many motifs in the ATP7A structure are conserved:[6]
- The TGEA motif lies in the loop on the cytosolic side between transmembrane segments 4 and 5 and is involved in energy transfer.
- The CPC motif located in transmembrane segment 6 is common for all heavy metal transporting ATPases.
Between transmembrane segments 6 and 7 is a large cytoplasmic loop, where three motifs are located: DKTG, SEHPL, and GDGXND.
- The DKTG motif is essential for the proper function of the ATPase. The aspartic acid (D) residue is phosphorylated during the transport cycles.
- The SEHPL motif only exists in heavy metal transporting P-type ATPases. Without the histidine (H) residue ATP7A may not function properly.
- The GDGXND motif near transmembrane segment 7 is thought to contain mainly α-helices and serves as a structural support.
The six Cu(I)-binding sites at the N-terminal bind one Cu(I) each. This binding site is not specific for Cu(I) and can bind various transition metal ions. Cd(II), Au(III) and Hg(II) bind to the binding site more tightly than does Zn(II), whereas Mn(II) and Ni(II) have lower affinities relative to Zn(II). In the case of Cu(I), a possible cooperative-binding mechanism is observed. When the Cu(I) concentration is low, Cu(I) has a lower affinity for ATP7A compared to Zn(II); as the Cu(I) concentration increases, a dramatic increasing affinity of Cu(I) for the protein is observed.[6]
# Conformational change
The two cysteine (C) residues in each Cu(I)-binding site are coordinated to Cu(I) with a S-Cu(I)-S angle between 120 and 180° and a Cu-S distance of 2.16 Å. Experimental results from a homologous protein ATP7B suggests that reducing reagents are involved, and upon Cu(I) binding the disulfide bonding between the cysteine residues is broken as cysteine starts to bind to Cu(I), leading to a series of conformational changes at the N-terminal of the protein, and possibly activating the Cu(I)-transporting activity of other cytosolic loops.[6]
Of the six copper(I)-binding sites, two are considered enough for the function of Cu(I) transport. The reason why there are six binding sites remains not fully understood. However, some scientists have proposed that the other four sites may serve as a Cu(I) concentration detector.[4]
# Transport mechanism
ATP7A belongs to a transporter family called P-type ATPases, which catalyze auto-phosphorylation of a key conserved aspartic acid (D) residue within the enzyme. The first step is ATP binding to the ATP-binding domain and Cu(I) binding to the transmembrane region. Then ATP7A is phosphorylated at the key aspartic acid (D) residue in the highly conserved DKTG motif, accompanied by Cu(I) release. A subsequent dephosphorylation of the intermediate finishes the catalytic cycle. Within each cycle, ATP7A interconverts between at least two different conformations, E1 and E2. In the E1 state, Cu(I) is tightly bound to the binding sites on the cytoplasmic side; in the E2 state, the affinity of ATP7A for Cu(I) decreases and Cu(I) is released on the extracellular side.[8]
# Function
ATP7A is important for regulating copper Cu(I) in mammals.[5] This protein is found in most tissues, but it is not expressed in the liver.[6] In the small intestine, the ATP7A protein helps control the absorption of Cu(I) from food. After Cu(I) ions are absorbed into enterocytes, ATP7A is required to transfer them across the basolateral membrane into the circulation.[4]
In other organs and tissues, the ATP7A protein has a dual role and shuttles between two locations within the cell. The protein normally resides in a cell structure called the Golgi apparatus, which modifies and transports newly produced enzymes and other proteins. Here, ATP7A supplies Cu(I) to certain enzymes (e.g. peptidyl-α-monooxygenase, tyrosinase, and lysyl oxidase[4]) that are critical for the structures and functions of brain, bone, skin, hair, connective tissue, and the nervous system. If Cu(I) levels in the cell environment are elevated, however, ATP7A moves to the cell membrane and eliminates excess Cu(I) from the cell.[3][5]
The functions of ATP7A in some tissues of the human body are as follows:[5]
# Interactions
ATP7A has been shown to interact with ATOX1 and GLRX. Antioxidant 1 copper chaperone (ATOX1) is required to maintain Cu(I) copper homeostasis in the cell. It can bind and transport cytosolic Cu(I) to ATP7A in the trans-Golgi-network. Glutaredoxin-1 (GRX1) has is also essential for ATP7A function. It promotes Cu(I) binding for subsequent transport by catalyzing the reduction of disulfide bridges. It may also catalyze de-glutathionylation reaction of the C (cysteine) residues within the six Cu(I)-binding motifs GMTCXXC.[5]
# Clinical significance
Menkes disease is caused by mutations in the ATP7A gene.[9] Researchers have identified different ATP7A mutations that cause Menkes disease and occipital horn syndrome (OHS), the milder form of Menkes disease. Many of these mutations delete part of the gene and are predicted to produce a shortened ATP7A protein that is unable to transport Cu(I). Other mutations insert additional DNA base pairs or use the wrong base pairs, which leads to ATP7A proteins that do not function properly.[2]
The altered proteins that result from ATP7A mutations impair the absorption of copper from food, fail to supply copper to certain enzymes, or get stuck in the cell membrane, unable to shuttle back and forth from the Golgi. As a result of the disrupted activity of the ATP7A protein, copper is poorly distributed to cells in the body. Copper accumulates in some tissues, such as the small intestine and kidneys, while the brain and other tissues have unusually low levels.[3][4] The decreased supply of copper can reduce the activity of numerous copper-containing enzymes that are necessary for the structure and function of bone, skin, hair, blood vessels, and the nervous system.[3][5] Copper is also critical for the propagation of prion proteins, and mice with mutations in Atp7a have a delayed onset of prion disease. [10]
# Inhibition
A proton pump inhibitor, Omeprazole, has been shown to block ATP7A, in addition to its more established role of blocking ATP4A. | https://www.wikidoc.org/index.php/ATP7A | |
f7888ecc5de4d03b3ecc05f0c9e8653dcee0a379 | wikidoc | AURKC | AURKC
Serine/threonine-protein kinase 13 is an enzyme that in humans is encoded by the AURKC gene.
# Function
This gene encodes a member of the highly conserved Aurora subfamily of serine/threonine protein kinases with two other members, Aurora A and Aurora B. The encoded protein is a chromosomal passenger protein that forms complexes with Aurora-B and inner centromere proteins and may play a role in organizing microtubules in relation to centrosome/spindle function during mitosis. This gene is overexpressed in several cancer cell lines, suggesting an involvement in oncogenic signal transduction. Alternative splicing results in multiple transcript variants.
# Function
Temporal expression patterns and subcellular localization of Aurora kinases in mitotic cells from G2 to cytokinesis indicate association with mitotic and meiotic structure. Although yeast contain only one Aurora kinase and C. elegans and Drosophila contain only two, mammals have three Aurora kinases with 67-76% homology that are structurally similar and localize similarly.
Aurora C localizes to the centrosome and then to the midzone of mitotic cells from anaphase to cytokinesis. It is expressed about an order of magnitude less than Aurora B in diploid human fibroblasts, with mRNA and protein concentrations peaking during the G2/M phase. Aurora C levels, however, peak after those of Aurora B later in the M phase. While Aurora A and B are expressed in mitotic somatic cells, Aurora C is more often expressed during meiosis (spermatogenesis and oogenesis).
Aurora B kinase regulates kinetochore maturation, destabilization of improper kinetochore-microtubule attachments, and spindle assembly checkpoint (SAC), central spindle organization, and cytokinesis. Aneuploidy results from independent and simultaneous inhibition of Aurora B and Aurora C. Slattery et al. found that they have overlapping functions and that Aurora C was able to rescue Aurora B-deficient mitotic cells from aneuploidy.
# Clinical Significance
Expression is typically limited to meiotic cells, but overexpression occurs in some cancer cell lines. PLZF, a transcription repressor, and its CpG island methylation are the most studied modes of regulating AURKC regulation. Although all of the Aurora kinases are overexpressed in many cancer cell lines, only Aurora A and C possess oncogenic activity, producing multinucleated cells and tumors in vivo when overexpressed. When cells overexpressing Aurora C were treated with nocodazole to turn on the SAC, Aurora B protein stability and activity decreased. This then prevented activation of SAC protein BubR1 and phosphorylation of histone H3 and MCAK.
Inactivating mutations of Aurora C have been shown to cause infertility in men characterized by macrocephalic and multiflagellular spermatozoa. Homozygous and heterozygous c.144delC mutation in the AURKC gene was found with an allelic frequency of 2.14% in Moroccan men with unexplained spermatogenic failure. The heterozygous state had a frequency of 1% in normospermic fertile men. Although c.144delC represents 85.5% of mutant alleles, the nonsense mutation p.Y248- (13% of all mutant alleles) is present in both European and African men and can lead to infertility. Klinefelter syndrome and Y chromosome microdeletion analyses are the most common genetic tests offered to infertile men, but AURKC and DPY19L2 defects are the leading cause of infertility in North African men.
# Interactions
Both Aurora B and C interact with the inner centromere protein (INCENP) from the C-terminal to the conserved IN box domain, but Aurora B preferentially binds INCENP. The chromosomal passenger complex (CPC), essential for chromosome segregation, contains the four subunits: the Aurora kinase, INCENP, survivin, and borealin (also known as dasra). Co-expression of Aurora B and C in vivo interferes with INCENP binding, localization, and stability. | AURKC
Serine/threonine-protein kinase 13 is an enzyme that in humans is encoded by the AURKC gene.[1][2]
# Function
This gene encodes a member of the highly conserved Aurora subfamily of serine/threonine protein kinases with two other members, Aurora A and Aurora B. The encoded protein is a chromosomal passenger protein that forms complexes with Aurora-B and inner centromere proteins and may play a role in organizing microtubules in relation to centrosome/spindle function during mitosis. This gene is overexpressed in several cancer cell lines, suggesting an involvement in oncogenic signal transduction. Alternative splicing results in multiple transcript variants.[2]
# Function
Temporal expression patterns and subcellular localization of Aurora kinases in mitotic cells from G2 to cytokinesis indicate association with mitotic and meiotic structure.[3] Although yeast contain only one Aurora kinase and C. elegans and Drosophila contain only two, mammals have three Aurora kinases with 67-76% homology that are structurally similar and localize similarly.[4]
Aurora C localizes to the centrosome and then to the midzone of mitotic cells from anaphase to cytokinesis. It is expressed about an order of magnitude less than Aurora B in diploid human fibroblasts, with mRNA and protein concentrations peaking during the G2/M phase. Aurora C levels, however, peak after those of Aurora B later in the M phase. While Aurora A and B are expressed in mitotic somatic cells, Aurora C is more often expressed during meiosis (spermatogenesis and oogenesis).[5]
Aurora B kinase regulates kinetochore maturation, destabilization of improper kinetochore-microtubule attachments, and spindle assembly checkpoint (SAC), central spindle organization, and cytokinesis. Aneuploidy results from independent and simultaneous inhibition of Aurora B and Aurora C. Slattery et al. found that they have overlapping functions and that Aurora C was able to rescue Aurora B-deficient mitotic cells from aneuploidy.[6]
# Clinical Significance
Expression is typically limited to meiotic cells, but overexpression occurs in some cancer cell lines.[7][8][9][10][11] PLZF, a transcription repressor, and its CpG island methylation are the most studied modes of regulating AURKC regulation.[12] Although all of the Aurora kinases are overexpressed in many cancer cell lines, only Aurora A and C possess oncogenic activity, producing multinucleated cells and tumors in vivo when overexpressed.[5] When cells overexpressing Aurora C were treated with nocodazole to turn on the SAC, Aurora B protein stability and activity decreased. This then prevented activation of SAC protein BubR1 and phosphorylation of histone H3 and MCAK.[13]
Inactivating mutations of Aurora C have been shown to cause infertility in men characterized by macrocephalic and multiflagellular spermatozoa. Homozygous and heterozygous c.144delC mutation in the AURKC gene was found with an allelic frequency of 2.14% in Moroccan men with unexplained spermatogenic failure. The heterozygous state had a frequency of 1% in normospermic fertile men.[14] Although c.144delC represents 85.5% of mutant alleles, the nonsense mutation p.Y248* (13% of all mutant alleles) is present in both European and African men and can lead to infertility.[15] Klinefelter syndrome and Y chromosome microdeletion analyses are the most common genetic tests offered to infertile men, but AURKC and DPY19L2 defects are the leading cause of infertility in North African men.[13]
# Interactions
Both Aurora B and C interact with the inner centromere protein (INCENP) from the C-terminal to the conserved IN box domain, but Aurora B preferentially binds INCENP. The chromosomal passenger complex (CPC), essential for chromosome segregation, contains the four subunits: the Aurora kinase, INCENP, survivin, and borealin (also known as dasra).[16][17] Co-expression of Aurora B and C in vivo interferes with INCENP binding, localization, and stability.[3] | https://www.wikidoc.org/index.php/AURKC | |
6d552d428b1804458bb97558b7959bbb05eee70a | wikidoc | AXIN1 | AXIN1
Axin-1 is a protein that in humans is encoded by the AXIN1 gene.
# Function
This gene encodes a cytoplasmic protein which contains a regulation of G-protein signaling (RGS) domain and a dishevelled and axin (DIX) domain. The encoded protein interacts with adenomatosis polyposis coli, catenin (cadherin-associated protein) beta 1, glycogen synthase kinase 3 beta, protein phosphatase 2, and itself. This protein functions as a negative regulator of the wingless-type MMTV integration site family, member 1 (WNT) signaling pathway and can induce apoptosis. The crystal structure of a portion of this protein, alone and in a complex with other proteins, has been resolved. Mutations in this gene have been associated with hepatocellular carcinoma, hepatoblastomas, ovarian endometriod adenocarcinomas, and medulloblastomas. Two transcript variants encoding distinct isoforms have been identified for this gene.
# Structure
The full-length human protein comprises 862 amino acids with a (predicted) molecular mass of 96 kDa. The N-terminal RGS domain, a GSK3 kinase interacting peptide of Axin1 and homologs of the C-terminal DIX domains have been solved at atomic resolution. Large WNT-downregulating central regions have been characterized as intrinsically disordered by biophysical experiments and bioinformatic analysis. Biophysical destabilization of the folded RGS domain induces formation of nanoaggregates that expose and locally concentrate intrinsically disordered regions, which in turn misregulate Wnt signalling. Many other large IDPs are affected by missense mutations, such as BRCA1, Adenomatous polyposis coli(APC), CREB-binding protein/(CBP) and might be affected in similar ways by missense mutations of their folded domains.
# Interactions
AXIN1 has been shown to interact with:
- APC,
- CTNNB1,
- CSNK1E,
- CSNK1A1,
- DVL1,
- GSK3B,
- LRP5,
- MAP3K1,
- PPP2R5A, and
- TSC2. | AXIN1
Axin-1 is a protein that in humans is encoded by the AXIN1 gene.[1]
# Function
This gene encodes a cytoplasmic protein which contains a regulation of G-protein signaling (RGS) domain and a dishevelled and axin (DIX) domain. The encoded protein interacts with adenomatosis polyposis coli, catenin (cadherin-associated protein) beta 1, glycogen synthase kinase 3 beta, protein phosphatase 2, and itself. This protein functions as a negative regulator of the wingless-type MMTV integration site family, member 1 (WNT) signaling pathway and can induce apoptosis. The crystal structure of a portion of this protein, alone and in a complex with other proteins, has been resolved. Mutations in this gene have been associated with hepatocellular carcinoma, hepatoblastomas, ovarian endometriod adenocarcinomas, and medulloblastomas. Two transcript variants encoding distinct isoforms have been identified for this gene.[2]
# Structure
The full-length human protein comprises 862 amino acids with a (predicted) molecular mass of 96 kDa. The N-terminal RGS domain, a GSK3 kinase interacting peptide of Axin1 and homologs of the C-terminal DIX domains have been solved at atomic resolution. Large WNT-downregulating central regions have been characterized as intrinsically disordered by biophysical experiments and bioinformatic analysis.[3] Biophysical destabilization of the folded RGS domain induces formation of nanoaggregates that expose and locally concentrate intrinsically disordered regions, which in turn misregulate Wnt signalling. Many other large IDPs are affected by missense mutations, such as BRCA1, Adenomatous polyposis coli(APC), CREB-binding protein/(CBP) and might be affected in similar ways by missense mutations of their folded domains.[4]
# Interactions
AXIN1 has been shown to interact with:
- APC,[5]
- CTNNB1,[5][6]
- CSNK1E,[7]
- CSNK1A1,[7]
- DVL1,[8][9]
- GSK3B,[5][10]
- LRP5,[8][11]
- MAP3K1,[7][12]
- PPP2R5A,[13] and
- TSC2.[10] | https://www.wikidoc.org/index.php/AXIN1 | |
fb9cdc67238193eee821e893b83d929c6741ccfc | wikidoc | AXIN2 | AXIN2
Axin-2 also known as axin-like protein (Axil) or axis inhibition protein 2 (AXIN2) or conductin is a protein that in humans is encoded by the AXIN2 gene.
# Function
The Axin-related protein, Axin2, presumably plays an important role in the regulation of the stability of beta-catenin in the Wnt signaling pathway, like its rodent homologs, mouse conductin/rat axil. In mouse, conductin organizes a multiprotein complex of APC (adenomatous polyposis of the colon), beta-catenin, glycogen synthase kinase 3-beta, and conductin, which leads to the degradation of beta-catenin.
# Clinical significance
The deregulation of beta-catenin is an important event in the genesis of a number of malignancies. The AXIN2 gene has been mapped to 17q23-q24, a region that shows frequent loss of heterozygosity in breast cancer, neuroblastoma, and other tumors. Mutations in this gene have been associated with colorectal cancer with defective mismatch repair.
The most critical events of teeth, lip and palate formation occur almost concurrently. Hypodontia, defined as the congenital lack of one or more permanent teeth, is the most common dental abnormality found in humans and affects approximately 20% of the population worldwide. AXIS inhibition protein 2 (AXIN2) gene polymorphic variants may be associated with both hypodontia and oligodontia (characterized by the lack of six or more permanent teeth). Mutations of this gene have been found in individuals with colorectal carcinomas and liver tumors.
An AXIN2 mutation (1966C>T) detected in a Finnish family was associated with both tooth agenesis and colon neoplasia. In essence, the mutation seems to disrupt tooth development early in life and later contributes to the emergence of polyps and eventually colon cancer, an observation that suggests that the lack of permanent teeth may be an indicator of colon cancer susceptibility. Dentists may at the very least need to remain aware of the possible association, to be able to detect such cases of tooth agenesis and forward the patient to more complete genetic diagnostic examinations. This is a simple example of how molecular genetic discoveries today interact with traditional disciplines (Longtin, 2004).
# Interactions
AXIN2 has been shown to interact with GSK3B. | AXIN2
Axin-2 also known as axin-like protein (Axil) or axis inhibition protein 2 (AXIN2) or conductin is a protein that in humans is encoded by the AXIN2 gene.[1][2]
# Function
The Axin-related protein, Axin2, presumably plays an important role in the regulation of the stability of beta-catenin in the Wnt signaling pathway, like its rodent homologs, mouse conductin/rat axil. In mouse, conductin organizes a multiprotein complex of APC (adenomatous polyposis of the colon), beta-catenin, glycogen synthase kinase 3-beta, and conductin, which leads to the degradation of beta-catenin.[2]
# Clinical significance
The deregulation of beta-catenin is an important event in the genesis of a number of malignancies. The AXIN2 gene has been mapped to 17q23-q24, a region that shows frequent loss of heterozygosity in breast cancer, neuroblastoma, and other tumors. Mutations in this gene have been associated with colorectal cancer with defective mismatch repair.[2]
The most critical events of teeth, lip and palate formation occur almost concurrently. Hypodontia, defined as the congenital lack of one or more permanent teeth, is the most common dental abnormality found in humans and affects approximately 20% of the population worldwide.[3] AXIS inhibition protein 2 (AXIN2) gene polymorphic variants may be associated with both hypodontia and oligodontia (characterized by the lack of six or more permanent teeth).[4][5] Mutations of this gene have been found in individuals with colorectal carcinomas and liver tumors.[6]
An AXIN2 mutation (1966C>T) detected in a Finnish family was associated with both tooth agenesis and colon neoplasia. In essence, the mutation seems to disrupt tooth development early in life and later contributes to the emergence of polyps and eventually colon cancer, an observation that suggests that the lack of permanent teeth may be an indicator of colon cancer susceptibility.[4] Dentists may at the very least need to remain aware of the possible association, to be able to detect such cases of tooth agenesis and forward the patient to more complete genetic diagnostic examinations. This is a simple example of how molecular genetic discoveries today interact with traditional disciplines (Longtin, 2004).
# Interactions
AXIN2 has been shown to interact with GSK3B.[7][8] | https://www.wikidoc.org/index.php/AXIN2 | |
f7f95b584c03b73cc846e373a19d42d67351a680 | wikidoc | Dream | Dream
Dreams are the images, thoughts and feelings experienced while asleep, particularly strongly associated with rapid eye movement sleep. The contents and biological purposes of dreams are not fully understood, though they have been a topic of speculation and interest throughout recorded history. The scientific study of dreams is known as oneirology.
# Neurology of sleep and dreams
There is no universally agreed biological definition of dreaming. General observation shows that dreams are strongly associated with rapid eye movement (REM) sleep, during which an electroencephalogram shows brain activity to be most like wakefulness. Participant-nonremembered dreams during non-REM sleep are normally more mundane in comparison. During a typical lifespan, a human spends a total of about six years dreaming (which is about 2 hours each night). It is unknown where in the brain dreams originate, if there is a single origin for dreams or if multiple portions of the brain are involved, or what the purpose of dreaming is for the body or mind.
During REM sleep, the release of certain neurotransmitters is completely suppressed. As a result, motor neurons are not stimulated, a condition known as REM atonia. This prevents dreams from resulting in dangerous movements of the body.
## Discovery of REM
In 1953 Eugene Aserinsky discovered REM sleep while working in the surgery of his PhD advisor. Aserinsky noticed that the sleepers' eyes fluttered beneath their closed eyelids, later using a polygraph machine to record their brain waves during these periods. In one session he awakened a subject who was crying and wailing out during REM and confirmed his suspicion that dreaming was occurring. In 1953 Aserinsky and his advisor published the ground-breaking study in Science.
# Dream theories
## Activation-synthesis
In 1976, J. Allan Hobson and Robert McCarley proposed a new theory that changed dream research, challenging the previously held Freudian view of dreams as unconscious wishes to be interpreted. The activation synthesis theory asserts that the sensory experiences are fabricated by the cortex as a means of interpreting chaotic signals from the pons. They propose that in REM sleep, the ascending cholinergic PGO (ponto-geniculo-occipital) waves stimulate higher midbrain and forebrain cortical structures, producing rapid eye movements. The activated forebrain then synthesizes the dream out of this internally generated information. They assume that the same structures that induce REM sleep also generate sensory information.
Hobson and McCarly's 1976 research suggested that the signals interpreted as dreams originated in the brain stem during REM sleep. However, research by Mark Solms suggests that dreams are generated in the forebrain, and that REM sleep and dreaming are not directly related. While working in the neurosurgery department at hospitals in Johannesburg and London, Solms had access to patients with various brain injuries. He began to question patients about their dreams and confirmed that patients with damage to the parietal lobe stopped dreaming; this finding was in line with Hobson's 1977 theory. However, Solms did not encounter cases of loss of dreaming with patients having brain stem damage. This observation forced him to question Hobson's prevailing theory which marked the brain stem as the source of the signals interpreted as dreams. Solms viewed the idea of dreaming as a function of many complex brain structures as validating Freudian dream theory, an idea that drew criticism from Hobson. Unhappy about Holmes' attempts at discrediting him, Solms, along with partner Edward Nadar, undertook a series of traumatic-injury impact studies using several different species of primates, particularly howler monkeys, in order to more fully understand the role brain damage plays in dream pathology. Solms' experiments proved inconclusive, however, as the high mortality rate associated with using an hydraulic impact pin to artificially produce brain damage in test subjects meant that his final candidate pool was too small to satisfy the requirements of the scientific method.
## Continual-activation
Combining Hobson's activation synthesis hypothesis with Solms's findings, the continual-activation theory of dreaming presented by Jie Zhang proposes that dreaming is a result of brain activation and synthesis; at the same time, dreaming and REM sleep are controlled by different brain mechanisms. Zhang hypothesizes that the function of sleep is to process, encode, and transfer the data from the temporary memory to the long-term memory, though there is not much evidence backing up this so-called "consolidation." Non-REM sleep processes the conscious-related memory (declarative memory), and REM sleep processes the unconscious related memory (procedural memory).
Zhang assumes that during REM sleep, the unconscious part of a brain is busy processing the procedural memory; meanwhile, the level of activation in the conscious part of the brain will descend to a very low level as the inputs from the sensory are basically disconnected. This will trigger the "continual-activation" mechanism to generate a data stream from the memory stores to flow through the conscious part of the brain. Zhang suggests that this pulse-like brain activation is the inducer of each dream. He proposes that, with the involvement of the brain associative thinking system, dreaming is, thereafter, self-maintained with the dreamer's own thinking until the next pulse of memory insertion. This explains why dreams have both characteristics of continuity (within a dream) and sudden changes (between two or more dreams).
## Dreams and memory
Eugen Tarnow suggests that dreams are ever-present excitations of long-term memory, even during waking life. The strangeness of dreams is due to the format of long-term memory, reminiscent of Penfield & Rasmussen’s findings that electrical excitations of the cortex give rise to experiences similar to dreams. During waking life an executive function interprets long term memory consistent with reality checking. Tarnow's theory is a reworking of Freud's theory of dreams in which Freud's unconscious is replaced with the long-term memory system and Freud's “Dream Work” describes the structure of long-term memory.
### Hippocampus and memory
A 2001 study showed evidence that illogical locations, characters, and dream flow may help the brain strengthen the linking and consolidation of semantic memories. These conditions may occur because, during REM sleep, the flow of information between the hippocampus and neocortex is reduced. Increasing levels of the stress hormone cortisol late in sleep (often during REM sleep) cause this decreased communication. One stage of memory consolidation is the linking of distant but related memories. Payne and Nadel hypothesize that these memories are then consolidated into a smooth narrative, similar to a process that happens when memories are created under stress.
## Functional hypotheses
There are many hypotheses about the function of dreams, including:
- During the night there may be many external stimuli bombarding the senses, but the mind interprets the stimulus and makes it a part of a dream in order to ensure continued sleep. The mind will, however, awaken an individual if they are in danger or if trained to respond to certain sounds, such as a baby crying.
- Dreams allow the repressed parts of the mind to be satisfied through fantasy while keeping the conscious mind from thoughts that would suddenly cause one to awaken from shock.
- Freud suggested that bad dreams let the brain learn to gain control over emotions resulting from distressing experiences.
- Jung suggested that dreams may compensate for one-sided attitudes held in waking consciousness.
- Ferenczi proposed that the dream, when told, may communicate something that is not being said outright.
- Dreams are like the cleaning-up operations of computers when they are off-line, removing parasitic nodes and other "junk" from the mind during sleep.
- Dreams create new ideas through the generation of random thought mutations. Some of these may be rejected by the mind as useless, while others may be seen as valuable and retained. Blechner calls this the theory of "Oneiric Darwinism."
- Dreams regulate mood.
- Hartmann says dreams may function like psychotherapy, by "making connections in a safe place" and allowing the dreamer to integrate thoughts that may be dissociated during waking life.
- More recent research by Griffin has led to the formulation of the 'expectation fulfillment theory of dreaming', which suggests that dreaming metaphorically completes patterns of emotional expectation and lowers stress levels.
- Coutts hypothesizes that dreams modify and test mental schemas during sleep during a process he calls emotional selection, and that only schema modifications that appear emotionally adaptive during dream tests are selected for retention, while those that appear maladaptive are abandoned or further modified and tested.
## Dreams and psychosis
A number of thinkers have commented on the similarities between the phenomenology of dreams and that of psychosis. Features common to the two states include thought disorder, flattened or inappropriate affect (emotion), and hallucination. Among philosophers, Kant, for example, wrote that ‘the lunatic is a wakeful dreamer’. Schopenhauer said: ‘A dream is a short-lasting psychosis, and a psychosis is a long-lasting dream.’In the field of psychoanalysis, Freud wrote: ‘A dream then, is a psychosis’,and Jung: ‘Let the dreamer walk about and act like one awakened and we have the clinical picture of dementia praecox.’
McCreery
has sought to explain these similarities by reference to the fact, documented by Oswald, that sleep can supervene as a reaction to extreme stress and hyper-arousal. McCreery adduces evidence that psychotics are people with a tendency to hyper-arousal, and suggests that this renders them prone to what Oswald calls ‘micro-sleeps’ during waking life. He points in particular to the paradoxical finding of Stevens and Darbyshire that patients suffering from catatonia can be roused from their seeming stupor by the administration of sedatives rather than stimulants.
# Cultural history
Dreams have a long history both as a subject of conjecture and as a source of inspiration. Throughout their history, people have sought meaning in dreams or divination through dreams. They have been described physiologically as a response to neural processes during sleep, psychologically as reflections of the subconscious, and spiritually as messages from God or predictions of the future. Many cultures practiced dream incubation, with the intention of cultivating dreams that were prophetic or contained messages from the divine.
# Dream content
From the 1940s to 1985, Calvin S. Hall collected more than 50,000 dream reports at Western Reserve University. In 1966 Hall and Van De Castle published The Content Analysis of Dreams in which they outlined a coding system to study 1,000 dream reports from college students. It was found that people all over the world dream of mostly the same things. Hall's complete dream reports became publicly available in the mid-1990s by Hall's protégé William Domhoff, allowing further different analysis.
Personal experiences from the last day or week are frequently incorporated into dreams.
## Emotions
The most common emotion experienced in dreams is anxiety. Negative emotions are more common than positive feelings. The U.S. ranks the highest amongst industrialized nations for aggression in dreams with 50 percent of U.S. males reporting aggression in dreams, compared to 32 percent for Dutch men.
## Sexual content
The Hall data analysis shows that sexual dreams occur no more than 90 percent of the time and are more prevalent in young to mid teens. Another study showed that 8% of men's and women's dreams have sexual content. In some cases, sexual dreams may result in orgasm or nocturnal emission. These are commonly known as wet dreams.
## Recurring dreams
While the content of most dreams is dreamt only once, many people experience recurring dreams—that is, the same dream narrative is experienced over different occasions of sleep. Up to 70% of females and 65% of males report recurrent dreams.
## Common themes
Content-analysis studies have identified common reported themes in dreams. These include: situations relating to school, being chased, running slowly in place, sexual experiences, falling, arriving too late, a person now alive being dead, teeth falling out, flying, embarrassing moments, failing an examination, not being able to move, not being able to focus vision and car accidents. Twelve percent of people dream only in black and white.
# Relationship with mental illness
There is evidence that certain medical conditions (normally only neurological conditions) can impact dreams. For instance, people with synesthesia have never reported black-and-white dreaming, and often have a difficult time imagining the idea of dreaming in only black and white.
Therapy for recurring nightmares (often associated with posttraumatic stress disorder) can include imagining alternative scenarios that could begin at each step of the dream.
# Dream interpretation
Dreams were historically used for healing (as in the asclepieions found in the ancient Greek temples of Asclepius) as well as for guidance or divine inspiration. Some Native American tribes used vision quests as a rite of passage, fasting and praying until an anticipated guiding dream was received, to be shared with the rest of the tribe upon their return.
During the late 19th and early 20th centuries, both Sigmund Freud and Carl Jung identified dreams as an interaction between the unconscious and the conscious. They also assert together that the unconscious is the dominant force of the dream, and in dreams it conveys its own mental activity to the perceptive faculty. While Freud felt that there was an active censorship against the unconscious even during sleep, Jung argued that the dream's bizarre quality is an efficient language, comparable to poetry and uniquely capable of revealing the underlying meaning.
Fritz Perls presented his theory of dreams as part of the holistic nature of Gestalt therapy. Dreams are seen as projections of parts of the self that have been ignored, rejected, or suppressed. Jung argued that one could consider every person in the dream to represent an aspect of the dreamer, which he called the subjective approach to dreams. Perls expanded this point of view to say that even inanimate objects in the dream may represent aspects of the dreamer. The dreamer may therefore be asked to imagine being an object in the dream and to describe it, in order to bring into awareness the characteristics of the object that correspond with the dreamer's personality.
# Other associated phenomena
## Lucid dreaming
Lucid dreaming is the conscious perception of one's state while dreaming. In this state a person usually has control over characters and the environment of the dream as well as the dreamer's own actions within the dream. The occurrence of lucid dreaming has been scientifically verified.
"Oneironaut" is a term sometimes used for those who explore the world of dreams. For example, dream researcher Stephen LaBerge uses the term. It is often associated with lucid dreaming in particular.
## Dreams of absent-minded transgression
Dreams of absent-minded transgression (DAMT) are dreams wherein the dreamer absentmindedly performs an action that he or she has been trying to stop (one classic example is of a quitting smoker having dreams of lighting a cigarette). Subjects who have had DAMT have reported waking with intense feelings of guilt. One study found a positive association between having these dreams and successfully stopping the behavior.
## Dreaming and the "real world"
Dreams can link to actual sensations, such as the incorporation of environmental sounds into dreams such as hearing a phone ringing in a dream while it is ringing in reality, or dreaming of urination while wetting the bed. Except in the case of lucid dreaming, people dream without being aware that they are doing so. Some philosophers have concluded that what we think as the "real world" could be or is an illusion (an idea known as the skeptical hypothesis about ontology). The first recorded mention of the idea was by Zhuangzi, and was also discussed in Hinduism; Buddhism makes extensive use of the argument in its writings. It was formally introduced to western philosophy by Descartes in the 17th century in his Meditations on First Philosophy.
## Recalling dreams
The recall of dreams is extremely unreliable, though it is a skill that can be trained. Dreams can usually be recalled if a person is awakened while dreaming. Women tend to have more frequent dream recall than men. Dreams that are difficult to recall may be characterized by relatively little affect, and factors such as salience, arousal, and interference play a role in dream recall. A dream journal can be used to assist dream recall, for psychotherapy or entertainment purposes.
## Déjà vu
The theory of déjà vu dealing with dreams indicates that the feeling of having previously seen or experienced something could be attributed to having dreamt about a similar situation or place, and forgetting about it until one seems to be mysteriously reminded of the situation or place while awake.
## Dream pre-programming
Dream pre-programming is a hypnotic practice used among some medical and stage hypnotists. It allows the hypnotist to control (or let the patient control) their own dreams. One way that a hypnotist will use this is by telling the person that when they fall asleep that they see a button. And that if they want to enter "DreamScape" that they should press that button. Then they will enter a world just like Earth, but they will have complete control. They will control things with their mind. Dream pre-programming can also help someone for a test or a big event in life. The hypnotist would make the subject dream that event as going perfect, so the subject will get a level of confidence.
## Dream incorporation
In one use of the term, "dream incorporation" is a phenomenon whereby an external stimulus, usually an auditory one, becomes a part of a dream, eventually then awakening the dreamer. There is a famous painting by Salvador Dalí that depicts this concept, titled "Dream Caused by the Flight of a Bee around a Pomegranate a Second Before Awakening" (1944).
The term "dream incorporation" is also used in research examining the degree to which preceding daytime events become elements of dreams. Recent studies suggest that events in the day immediately preceding, and those about a week before, have the most influence . | Dream
Template:Search infobox
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Dreams are the images, thoughts and feelings experienced while asleep, particularly strongly associated with rapid eye movement sleep. The contents and biological purposes of dreams are not fully understood, though they have been a topic of speculation and interest throughout recorded history. The scientific study of dreams is known as oneirology.
# Neurology of sleep and dreams
There is no universally agreed biological definition of dreaming. General observation shows that dreams are strongly associated with rapid eye movement (REM) sleep, during which an electroencephalogram shows brain activity to be most like wakefulness. Participant-nonremembered dreams during non-REM sleep are normally more mundane in comparison.[1] During a typical lifespan, a human spends a total of about six years dreaming[2] (which is about 2 hours each night[3]). It is unknown where in the brain dreams originate, if there is a single origin for dreams or if multiple portions of the brain are involved, or what the purpose of dreaming is for the body or mind.
During REM sleep, the release of certain neurotransmitters is completely suppressed. As a result, motor neurons are not stimulated, a condition known as REM atonia. This prevents dreams from resulting in dangerous movements of the body.
## Discovery of REM
In 1953 Eugene Aserinsky discovered REM sleep while working in the surgery of his PhD advisor. Aserinsky noticed that the sleepers' eyes fluttered beneath their closed eyelids, later using a polygraph machine to record their brain waves during these periods. In one session he awakened a subject who was crying and wailing out during REM and confirmed his suspicion that dreaming was occurring.[4] In 1953 Aserinsky and his advisor published the ground-breaking study in Science.[5]
# Dream theories
## Activation-synthesis
In 1976, J. Allan Hobson and Robert McCarley proposed a new theory that changed dream research, challenging the previously held Freudian view of dreams as unconscious wishes to be interpreted. The activation synthesis theory asserts that the sensory experiences are fabricated by the cortex as a means of interpreting chaotic signals from the pons. They propose that in REM sleep, the ascending cholinergic PGO (ponto-geniculo-occipital) waves stimulate higher midbrain and forebrain cortical structures, producing rapid eye movements. The activated forebrain then synthesizes the dream out of this internally generated information. They assume that the same structures that induce REM sleep also generate sensory information.
Hobson and McCarly's 1976 research suggested that the signals interpreted as dreams originated in the brain stem during REM sleep. However, research by Mark Solms suggests that dreams are generated in the forebrain, and that REM sleep and dreaming are not directly related.[6] While working in the neurosurgery department at hospitals in Johannesburg and London, Solms had access to patients with various brain injuries. He began to question patients about their dreams and confirmed that patients with damage to the parietal lobe stopped dreaming; this finding was in line with Hobson's 1977 theory. However, Solms did not encounter cases of loss of dreaming with patients having brain stem damage. This observation forced him to question Hobson's prevailing theory which marked the brain stem as the source of the signals interpreted as dreams. Solms viewed the idea of dreaming as a function of many complex brain structures as validating Freudian dream theory, an idea that drew criticism from Hobson.[7] Unhappy about Holmes' attempts at discrediting him, Solms, along with partner Edward Nadar, undertook a series of traumatic-injury impact studies using several different species of primates, particularly howler monkeys, in order to more fully understand the role brain damage plays in dream pathology. Solms' experiments proved inconclusive, however, as the high mortality rate associated with using an hydraulic impact pin to artificially produce brain damage in test subjects meant that his final candidate pool was too small to satisfy the requirements of the scientific method.
## Continual-activation
Combining Hobson's activation synthesis hypothesis with Solms's findings, the continual-activation theory of dreaming presented by Jie Zhang proposes that dreaming is a result of brain activation and synthesis; at the same time, dreaming and REM sleep are controlled by different brain mechanisms. Zhang hypothesizes that the function of sleep is to process, encode, and transfer the data from the temporary memory to the long-term memory, though there is not much evidence backing up this so-called "consolidation." Non-REM sleep processes the conscious-related memory (declarative memory), and REM sleep processes the unconscious related memory (procedural memory).
Zhang assumes that during REM sleep, the unconscious part of a brain is busy processing the procedural memory; meanwhile, the level of activation in the conscious part of the brain will descend to a very low level as the inputs from the sensory are basically disconnected. This will trigger the "continual-activation" mechanism to generate a data stream from the memory stores to flow through the conscious part of the brain. Zhang suggests that this pulse-like brain activation is the inducer of each dream. He proposes that, with the involvement of the brain associative thinking system, dreaming is, thereafter, self-maintained with the dreamer's own thinking until the next pulse of memory insertion. This explains why dreams have both characteristics of continuity (within a dream) and sudden changes (between two or more dreams).[8][9]
## Dreams and memory
Eugen Tarnow suggests that dreams are ever-present excitations of long-term memory, even during waking life. The strangeness of dreams is due to the format of long-term memory, reminiscent of Penfield & Rasmussen’s findings that electrical excitations of the cortex give rise to experiences similar to dreams. During waking life an executive function interprets long term memory consistent with reality checking. Tarnow's theory is a reworking of Freud's theory of dreams in which Freud's unconscious is replaced with the long-term memory system and Freud's “Dream Work” describes the structure of long-term memory.[10]
### Hippocampus and memory
A 2001 study showed evidence that illogical locations, characters, and dream flow may help the brain strengthen the linking and consolidation of semantic memories. These conditions may occur because, during REM sleep, the flow of information between the hippocampus and neocortex is reduced.[11] Increasing levels of the stress hormone cortisol late in sleep (often during REM sleep) cause this decreased communication. One stage of memory consolidation is the linking of distant but related memories. Payne and Nadel hypothesize that these memories are then consolidated into a smooth narrative, similar to a process that happens when memories are created under stress.[12]
## Functional hypotheses
There are many hypotheses about the function of dreams, including:[13]
- During the night there may be many external stimuli bombarding the senses, but the mind interprets the stimulus and makes it a part of a dream in order to ensure continued sleep.[14] The mind will, however, awaken an individual if they are in danger or if trained to respond to certain sounds, such as a baby crying.
- Dreams allow the repressed parts of the mind to be satisfied through fantasy while keeping the conscious mind from thoughts that would suddenly cause one to awaken from shock.[15]
- Freud suggested that bad dreams let the brain learn to gain control over emotions resulting from distressing experiences.[13]
- Jung suggested that dreams may compensate for one-sided attitudes held in waking consciousness.[16]
- Ferenczi[17] proposed that the dream, when told, may communicate something that is not being said outright.
- Dreams are like the cleaning-up operations of computers when they are off-line, removing parasitic nodes and other "junk" from the mind during sleep.[18][19]
- Dreams create new ideas through the generation of random thought mutations. Some of these may be rejected by the mind as useless, while others may be seen as valuable and retained. Blechner[20] calls this the theory of "Oneiric Darwinism."
- Dreams regulate mood.[21]
- Hartmann[22] says dreams may function like psychotherapy, by "making connections in a safe place" and allowing the dreamer to integrate thoughts that may be dissociated during waking life.
- More recent research by Griffin has led to the formulation of the 'expectation fulfillment theory of dreaming', which suggests that dreaming metaphorically completes patterns of emotional expectation and lowers stress levels.[23][24]
- Coutts[25] hypothesizes that dreams modify and test mental schemas during sleep during a process he calls emotional selection, and that only schema modifications that appear emotionally adaptive during dream tests are selected for retention, while those that appear maladaptive are abandoned or further modified and tested.
## Dreams and psychosis
A number of thinkers have commented on the similarities between the phenomenology of dreams and that of psychosis. Features common to the two states include thought disorder, flattened or inappropriate affect (emotion), and hallucination. Among philosophers, Kant, for example, wrote that ‘the lunatic is a wakeful dreamer’.[26] Schopenhauer said: ‘A dream is a short-lasting psychosis, and a psychosis is a long-lasting dream.’[27]In the field of psychoanalysis, Freud wrote: ‘A dream then, is a psychosis’,[28]and Jung: ‘Let the dreamer walk about and act like one awakened and we have the clinical picture of dementia praecox.’[29]
McCreery[30][31]
has sought to explain these similarities by reference to the fact, documented by Oswald,[32] that sleep can supervene as a reaction to extreme stress and hyper-arousal. McCreery adduces evidence that psychotics are people with a tendency to hyper-arousal, and suggests that this renders them prone to what Oswald calls ‘micro-sleeps’ during waking life. He points in particular to the paradoxical finding of Stevens and Darbyshire[33] that patients suffering from catatonia can be roused from their seeming stupor by the administration of sedatives rather than stimulants.
# Cultural history
Dreams have a long history both as a subject of conjecture and as a source of inspiration. Throughout their history, people have sought meaning in dreams or divination through dreams. They have been described physiologically as a response to neural processes during sleep, psychologically as reflections of the subconscious, and spiritually as messages from God or predictions of the future. Many cultures practiced dream incubation, with the intention of cultivating dreams that were prophetic or contained messages from the divine.
# Dream content
From the 1940s to 1985, Calvin S. Hall collected more than 50,000 dream reports at Western Reserve University. In 1966 Hall and Van De Castle published The Content Analysis of Dreams in which they outlined a coding system to study 1,000 dream reports from college students.[34] It was found that people all over the world dream of mostly the same things. Hall's complete dream reports became publicly available in the mid-1990s by Hall's protégé William Domhoff, allowing further different analysis.
Personal experiences from the last day or week are frequently incorporated into dreams.[35]
## Emotions
The most common emotion experienced in dreams is anxiety. Negative emotions are more common than positive feelings.[34] The U.S. ranks the highest amongst industrialized nations for aggression in dreams with 50 percent of U.S. males reporting aggression in dreams, compared to 32 percent for Dutch men.[34]
## Sexual content
The Hall data analysis shows that sexual dreams occur no more than 90 percent of the time and are more prevalent in young to mid teens.[34] Another study showed that 8% of men's and women's dreams have sexual content.[36] In some cases, sexual dreams may result in orgasm or nocturnal emission. These are commonly known as wet dreams.[37]
## Recurring dreams
While the content of most dreams is dreamt only once, many people experience recurring dreams—that is, the same dream narrative is experienced over different occasions of sleep. Up to 70% of females and 65% of males report recurrent dreams.[38]
## Common themes
Content-analysis studies have identified common reported themes in dreams. These include: situations relating to school, being chased, running slowly in place, sexual experiences, falling, arriving too late, a person now alive being dead, teeth falling out, flying, embarrassing moments, failing an examination, not being able to move, not being able to focus vision and car accidents. Twelve percent of people dream only in black and white.[39]
# Relationship with mental illness
There is evidence that certain medical conditions (normally only neurological conditions) can impact dreams. For instance, people with synesthesia have never reported black-and-white dreaming, and often have a difficult time imagining the idea of dreaming in only black and white.[40]
Therapy for recurring nightmares (often associated with posttraumatic stress disorder) can include imagining alternative scenarios that could begin at each step of the dream.[41]
# Dream interpretation
Dreams were historically used for healing (as in the asclepieions found in the ancient Greek temples of Asclepius) as well as for guidance or divine inspiration. Some Native American tribes used vision quests as a rite of passage, fasting and praying until an anticipated guiding dream was received, to be shared with the rest of the tribe upon their return.[42]
During the late 19th and early 20th centuries, both Sigmund Freud and Carl Jung identified dreams as an interaction between the unconscious and the conscious. They also assert together that the unconscious is the dominant force of the dream, and in dreams it conveys its own mental activity to the perceptive faculty. While Freud felt that there was an active censorship against the unconscious even during sleep, Jung argued that the dream's bizarre quality is an efficient language, comparable to poetry and uniquely capable of revealing the underlying meaning.
Fritz Perls presented his theory of dreams as part of the holistic nature of Gestalt therapy. Dreams are seen as projections of parts of the self that have been ignored, rejected, or suppressed.[43] Jung argued that one could consider every person in the dream to represent an aspect of the dreamer, which he called the subjective approach to dreams. Perls expanded this point of view to say that even inanimate objects in the dream may represent aspects of the dreamer. The dreamer may therefore be asked to imagine being an object in the dream and to describe it, in order to bring into awareness the characteristics of the object that correspond with the dreamer's personality.
# Other associated phenomena
## Lucid dreaming
Lucid dreaming is the conscious perception of one's state while dreaming. In this state a person usually has control over characters and the environment of the dream as well as the dreamer's own actions within the dream.[44] The occurrence of lucid dreaming has been scientifically verified.[45]
"Oneironaut" is a term sometimes used for those who explore the world of dreams. For example, dream researcher Stephen LaBerge uses the term.[46] It is often associated with lucid dreaming in particular.
## Dreams of absent-minded transgression
Dreams of absent-minded transgression (DAMT) are dreams wherein the dreamer absentmindedly performs an action that he or she has been trying to stop (one classic example is of a quitting smoker having dreams of lighting a cigarette). Subjects who have had DAMT have reported waking with intense feelings of guilt. One study found a positive association between having these dreams and successfully stopping the behavior.[47]
## Dreaming and the "real world"
Dreams can link to actual sensations, such as the incorporation of environmental sounds into dreams such as hearing a phone ringing in a dream while it is ringing in reality, or dreaming of urination while wetting the bed. Except in the case of lucid dreaming, people dream without being aware that they are doing so. Some philosophers have concluded that what we think as the "real world" could be or is an illusion (an idea known as the skeptical hypothesis about ontology). The first recorded mention of the idea was by Zhuangzi, and was also discussed in Hinduism; Buddhism makes extensive use of the argument in its writings.[48] It was formally introduced to western philosophy by Descartes in the 17th century in his Meditations on First Philosophy.
## Recalling dreams
The recall of dreams is extremely unreliable, though it is a skill that can be trained. Dreams can usually be recalled if a person is awakened while dreaming.[41] Women tend to have more frequent dream recall than men. [41] Dreams that are difficult to recall may be characterized by relatively little affect, and factors such as salience, arousal, and interference play a role in dream recall. A dream journal can be used to assist dream recall, for psychotherapy or entertainment purposes.
## Déjà vu
The theory of déjà vu dealing with dreams indicates that the feeling of having previously seen or experienced something could be attributed to having dreamt about a similar situation or place, and forgetting about it until one seems to be mysteriously reminded of the situation or place while awake.[49]
## Dream pre-programming
Template:Unreferencedsection
Dream pre-programming is a hypnotic practice used among some medical and stage hypnotists. It allows the hypnotist to control (or let the patient control) their own dreams. One way that a hypnotist will use this is by telling the person that when they fall asleep that they see a button. And that if they want to enter "DreamScape" that they should press that button. Then they will enter a world just like Earth, but they will have complete control. They will control things with their mind. Dream pre-programming can also help someone for a test or a big event in life. The hypnotist would make the subject dream that event as going perfect, so the subject will get a level of confidence.
## Dream incorporation
In one use of the term, "dream incorporation" is a phenomenon whereby an external stimulus, usually an auditory one, becomes a part of a dream, eventually then awakening the dreamer. There is a famous painting by Salvador Dalí that depicts this concept, titled "Dream Caused by the Flight of a Bee around a Pomegranate a Second Before Awakening" (1944).
The term "dream incorporation" is also used in research examining the degree to which preceding daytime events become elements of dreams. Recent studies suggest that events in the day immediately preceding, and those about a week before, have the most influence .[35] | https://www.wikidoc.org/index.php/Abnormal_dreams | |
2f659406c15850bea40ab26067509312b8580440 | wikidoc | Pulse | Pulse
# Overview
Pulse is the throbbing of the arteries as an effect of the heart beat. It can be felt in any place that allows for an artery to be compressed against a bone, such as at the neck (carotid artery), at the wrist (radial artery), behind the knee (popliteal artery), on the inside of the elbow (brachial artery), and near the ankle joint (posterior tibial artery). The pulse rate can also be measured by measuring the heart beats directly (the apical pulse).
Pressure waves move the artery walls, which are pliable; these waves are not caused by the forward movement of the blood. When the heart contracts, blood is ejected into the aorta and the aorta stretches. At this point, the wave of distention (pulse wave) is pronounced but relatively slow-moving (3–6 m/s). As it travels towards the peripheral blood vessels, it gradually diminishes and becomes faster. In the large arterial branches, its velocity is 7–10 m/s; in the small arteries, it is 15–35 m/s. The pressure pulse is transmitted fifteen or more times more rapidly than the blood flow.
Pulse is also used, although incorrectly, to denote the frequency of the heart beat, usually measured in beats per minute. In most people, the pulse is an accurate measure of heart rate. Under certain circumstances, including arrhythmias, some of the heart beats are ineffective, and the aorta is not stretched enough to create a palpable pressure wave. The pulse is too irregular and the heart rate can be (much) higher than the pulse rate. In this case, the heart rate should be determined by auscultation of the heart apex, in which case it is not the pulse. The pulse deficit (difference between heart beats and pulsations at the periphery) should be determined by simultaneous palpation at the radial artery and auscultation at the heart apex.
A normal pulse rate for a healthy adult, while resting, can range from 60 to 100 beats per minute (BPM), although well conditioned athletes may have a healthy pulse rate lower than 60 BPM. Bradycardia occurs when the pulse rate is below 60 per minute, whereas tachycardia occurs when the rate is above 100 BPM. During sleep, this can drop to as low as 40 BPM; during strenuous exercise, it can rise as high as 150–200 BPM. Generally, pulse rates are higher in infants and young children. The resting heart rate for an infant is usually close to an adult's pulse rate during strenuous exercise (average 110 BPM for an infant).
A collapsing pulse is a sign of hyperdynamic circulation.
# Common pulse sites
- Apical pulse: located in the 4th or 5th left intercostal space, just to the left of the sternum. In contrast with other pulse sites, the apical pulse site is unilateral, and measured not over an artery, but over the heart itself (more specifically, the apex of the heart).
- Brachial pulse: located between the biceps and triceps, on the medial side of the elbow cavity, frequently used in place of carotid pulse in infants (brachial artery)
- Carotid pulse: located in the neck (carotid artery). The carotid artery should be palpated gently and while the patient is sitting or lying down. Stimulating its baroreceptors with vigorous palpitation can provoke severe bradycardia or even stop the heart in some sensitive persons. Also, a person's two carotid arteries should not be palpated at the same time. Doing so may limit the flow of blood to the head, possibly leading to fainting or brain ischemia. It can be felt between the anterior border of the sternocleidomastoid muscle, above the hyoid bone and lateral to the thyroid cartilage.
- Dorsalis pedis pulse: located on top of the foot (dorsalis pedis artery).
- Facial pulse: located on the mandible (lower jawbone) on a line with the corners of the mouth (facial artery).
- Femoral pulse: located in the thigh, halfway between the pubic symphysis and anterior superior iliac spine (femoral artery).
- Popliteal pulse: located behind the knee in the popliteal fossa, found by holding the bent knee. The patient bends the knee at approximately 120°, and the physician holds it in both hands to find the popliteal artery in the pit behind the knee.
- Radial pulse: located on the thumb side of the wrist (radial artery). It can also be found in the anatomical snuff box.
- Temporal pulse: located on the temple directly in front of the ear (superficial temporal artery).
- Tibialis posterior pulse: located on the medial side of the ankle (facing inwards) behind the medial malleolus (posterior tibial artery).
- Ulnar pulse: located on the little finger side of the wrist(ulnar artery).
The ease of palpability of a pulse is dictated by the patient's blood pressure. If his or her systolic blood pressure is below 80 mmHg, the radial pulse will not be palpable. Below 70 mmHg, the brachial pulse will not be palpable. Below 60 mmHg, the carotid pulse will not be palpable. However, a study by the National Institutes of Health indicated that this method was not accurate enough and often overestimated a patient's systolic blood pressure. The lack of a palpable carotid pulse is often an indication of death.
# Reading a pulse
Pulses are manually palpated with fingers. When palpating the carotid artery, the femoral artery or the brachial artery, the thumb may be used. However, the thumb has its own pulse which can interfere with detecting the patient's pulse at other points, where two or three fingers should be used. Fingers or the thumb must be placed near an artery and pressed gently against a firm structure, usually a bone, in order to feel the pulse.
Make sure the person is calm and has been resting for 5 minutes before reading the pulse. Put the index and middle fingers over the pulse count, and count for 30 seconds, and afterwards multiply by 2, to get the pulse rate. If the person's pulse rate is irregular, count for a full minute, and do not multiply. Averaging multiple readings may give a more representative figure.
Home blood pressure measurement devices also typically give a pulse reading. | Pulse
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
# Overview
Pulse is the throbbing of the arteries as an effect of the heart beat. It can be felt in any place that allows for an artery to be compressed against a bone, such as at the neck (carotid artery), at the wrist (radial artery), behind the knee (popliteal artery), on the inside of the elbow (brachial artery), and near the ankle joint (posterior tibial artery). The pulse rate can also be measured by measuring the heart beats directly (the apical pulse).
Pressure waves move the artery walls, which are pliable; these waves are not caused by the forward movement of the blood. When the heart contracts, blood is ejected into the aorta and the aorta stretches. At this point, the wave of distention (pulse wave) is pronounced but relatively slow-moving (3–6 m/s). As it travels towards the peripheral blood vessels, it gradually diminishes and becomes faster. In the large arterial branches, its velocity is 7–10 m/s; in the small arteries, it is 15–35 m/s. The pressure pulse is transmitted fifteen or more times more rapidly than the blood flow.
Pulse is also used, although incorrectly, to denote the frequency of the heart beat, usually measured in beats per minute. In most people, the pulse is an accurate measure of heart rate. Under certain circumstances, including arrhythmias, some of the heart beats are ineffective, and the aorta is not stretched enough to create a palpable pressure wave. The pulse is too irregular and the heart rate can be (much) higher than the pulse rate. In this case, the heart rate should be determined by auscultation of the heart apex, in which case it is not the pulse. The pulse deficit (difference between heart beats and pulsations at the periphery) should be determined by simultaneous palpation at the radial artery and auscultation at the heart apex.
A normal pulse rate for a healthy adult, while resting, can range from 60 to 100 beats per minute (BPM), although well conditioned athletes may have a healthy pulse rate lower than 60 BPM. Bradycardia occurs when the pulse rate is below 60 per minute, whereas tachycardia occurs when the rate is above 100 BPM. During sleep, this can drop to as low as 40 BPM; during strenuous exercise, it can rise as high as 150–200 BPM. Generally, pulse rates are higher in infants and young children. The resting heart rate for an infant is usually close to an adult's pulse rate during strenuous exercise (average 110 BPM for an infant).
A collapsing pulse is a sign of hyperdynamic circulation.
# Common pulse sites
- Apical pulse: located in the 4th or 5th left intercostal space, just to the left of the sternum. In contrast with other pulse sites, the apical pulse site is unilateral, and measured not over an artery, but over the heart itself (more specifically, the apex of the heart).
- Brachial pulse: located between the biceps and triceps, on the medial side of the elbow cavity, frequently used in place of carotid pulse in infants (brachial artery)
- Carotid pulse: located in the neck (carotid artery). The carotid artery should be palpated gently and while the patient is sitting or lying down. Stimulating its baroreceptors with vigorous palpitation can provoke severe bradycardia or even stop the heart in some sensitive persons. Also, a person's two carotid arteries should not be palpated at the same time. Doing so may limit the flow of blood to the head, possibly leading to fainting or brain ischemia. It can be felt between the anterior border of the sternocleidomastoid muscle, above the hyoid bone and lateral to the thyroid cartilage.
- Dorsalis pedis pulse: located on top of the foot (dorsalis pedis artery).
- Facial pulse: located on the mandible (lower jawbone) on a line with the corners of the mouth (facial artery).
- Femoral pulse: located in the thigh, halfway between the pubic symphysis and anterior superior iliac spine (femoral artery).
- Popliteal pulse: located behind the knee in the popliteal fossa, found by holding the bent knee. The patient bends the knee at approximately 120°, and the physician holds it in both hands to find the popliteal artery in the pit behind the knee.
- Radial pulse: located on the thumb side of the wrist (radial artery). It can also be found in the anatomical snuff box.
- Temporal pulse: located on the temple directly in front of the ear (superficial temporal artery).
- Tibialis posterior pulse: located on the medial side of the ankle (facing inwards) behind the medial malleolus (posterior tibial artery).
- Ulnar pulse: located on the little finger side of the wrist(ulnar artery).
The ease of palpability of a pulse is dictated by the patient's blood pressure. If his or her systolic blood pressure is below 80 mmHg, the radial pulse will not be palpable. Below 70 mmHg, the brachial pulse will not be palpable. Below 60 mmHg, the carotid pulse will not be palpable. However, a study by the National Institutes of Health indicated that this method was not accurate enough and often overestimated a patient's systolic blood pressure.[1] The lack of a palpable carotid pulse is often an indication of death.
# Reading a pulse
Pulses are manually palpated with fingers. When palpating the carotid artery, the femoral artery or the brachial artery, the thumb may be used. However, the thumb has its own pulse which can interfere with detecting the patient's pulse at other points, where two or three fingers should be used. Fingers or the thumb must be placed near an artery and pressed gently against a firm structure, usually a bone, in order to feel the pulse.
Make sure the person is calm and has been resting for 5 minutes before reading the pulse. Put the index and middle fingers over the pulse count, and count for 30 seconds, and afterwards multiply by 2, to get the pulse rate. If the person's pulse rate is irregular, count for a full minute, and do not multiply. Averaging multiple readings may give a more representative figure.
Home blood pressure measurement devices also typically give a pulse reading. | https://www.wikidoc.org/index.php/Abnormal_pulsation | |
f8d1927850f404b77af9c6fc83491499f1602206 | wikidoc | Abuse | Abuse
# Background
Abuse refers to the use or treatment of something (a person, item, substance, concept, or vocabulary) that is seen as harmful.
# Types of Abuse
Several types of abuse include:
- Spiritual abuse: abusive or aberrational practices identified in the behavior and teachings of some churches, spiritual and religious organizations and groups.
- Sexual abuse: The improper use of another person for sexual purposes, generally without their consent or under physical or psychological pressure (also, child sexual abuse, whether abused by parents, those in loco parentis or strangers).
- Physical abuse: Where one person inflicts physical violence or pain on another.
- Verbal abuse: When a person uses profanity, demeaning talk, or threatening statements.
- Emotional abuse or psychological abuse: coercion, humiliation, intimidation, relational aggression, parental alienation or covert incest: Where one person uses emotional or psychological coercion to compel another to do something they do not want, or is not in their best interests; or when one person manipulates another's emotional or psychological state for their own ends (see battered person syndrome), or commits psychological aggression using ostensibly non-violent methods to inflict mental or emotional violence or pain on another.
- Drug abuse: the misuse of drugs, alcohol or other substances, usually a form of addiction. Law enforcement officials, among others, often define drug abuse as "any" use of illegal drugs, whether or not use is actually harmful to the user or to anyone else.
- Child abuse: Abuse, usually physical, emotional or sexual, directed at a child.
- Spousal abuse (or domestic violence): Abuse, usually physical, or psychological abuse, directed at one's domestic partner.
- Elder abuse: Abuse, most often physical or in the form of psychological threats, directed at the elderly, especially in nursing homes and similar institutions.
- Human rights abuse: Violation of human rights.
- Animal abuse: Abuse or cruelty directed at animals.
- Legal abuse: Vexatious litigation or malicious prosecution to retaliate, coerce, or emotionally/financially harm a person.
- Internet abuse includes a wide range of inappropriate online behavior, such as unsolicited promotional email, intrusion attempts, and phishing.
ca:Abús
de:Missbrauch
it:Abuso
he:התעללות
hu:Visszaélés
scn:Abbusu
simple:Abuse
yi:באלעסטיגן | Abuse
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
# Background
Abuse refers to the use or treatment of something (a person, item, substance, concept, or vocabulary) that is seen as harmful.
# Types of Abuse
Several types of abuse include:
- Spiritual abuse: abusive or aberrational practices identified in the behavior and teachings of some churches, spiritual and religious organizations and groups.
- Sexual abuse: The improper use of another person for sexual purposes, generally without their consent or under physical or psychological pressure (also, child sexual abuse, whether abused by parents, those in loco parentis or strangers).
- Physical abuse: Where one person inflicts physical violence or pain on another.
- Verbal abuse: When a person uses profanity, demeaning talk, or threatening statements.
- Emotional abuse or psychological abuse: coercion, humiliation, intimidation, relational aggression, parental alienation or covert incest: Where one person uses emotional or psychological coercion to compel another to do something they do not want, or is not in their best interests; or when one person manipulates another's emotional or psychological state for their own ends (see battered person syndrome), or commits psychological aggression using ostensibly non-violent methods to inflict mental or emotional violence or pain on another.
- Drug abuse: the misuse of drugs, alcohol or other substances, usually a form of addiction. Law enforcement officials, among others, often define drug abuse as "any" use of illegal drugs, whether or not use is actually harmful to the user or to anyone else.
- Child abuse: Abuse, usually physical, emotional or sexual, directed at a child.
- Spousal abuse (or domestic violence): Abuse, usually physical, or psychological abuse, directed at one's domestic partner.
- Elder abuse: Abuse, most often physical or in the form of psychological threats, directed at the elderly, especially in nursing homes and similar institutions.
- Human rights abuse: Violation of human rights.
- Animal abuse: Abuse or cruelty directed at animals.
- Legal abuse: Vexatious litigation or malicious prosecution to retaliate, coerce, or emotionally/financially harm a person.
- Internet abuse includes a wide range of inappropriate online behavior, such as unsolicited promotional email, intrusion attempts, and phishing.
Template:WikiDoc Sources
ca:Abús
de:Missbrauch
it:Abuso
he:התעללות
hu:Visszaélés
scn:Abbusu
simple:Abuse
yi:באלעסטיגן | https://www.wikidoc.org/index.php/Abuse | |
6385510024192985f546df3d0bc79e6fd815b841 | wikidoc | Acron | Acron
Acron, son of Xenon, was an eminent Greek physician born at Agrigentum. His exact date is not known; but, as he is mentioned as being contemporary with Empedocles, who died about the beginning of the Peloponnesian war, he must have lived in the fifth century BC. From Sicily he went to Athens, and there opened a philosophical school (Template:Polytonic).
It is said that he was in that city during the great plague (430 BC), and that large fires for the purpose of purifying the air were kindled in the streets by his direction, which proved of great service to several of the sick. It should however be borne in mind that there is no mention of this in Thucydides, and, if it is true that Empedocles or Simonides (who died in 467 BC) wrote the epitaph on Acron, it may be doubted whether he was in Athens at all during the plague.
On his return to his native country, the physician asked the senate for a spot of ground where he might build a family tomb. The request was refused at the suggestion of Empedocles, who conceived that such a grant for such a purpose would interfere with the principle of equality he was anxious to establish at Agrigentum. As the sarcastic epitaph on Acron is probably the most complete jeu de mots on record, and therefore defies all translation, it will be given in Greek to preserve the paronomasia of the original:
The second line was sometimes read thus:
Some persons attributed the whole epigram to Simonides.
Pliny considers him as the first of the Empirics. But this has been considered an error on the part of the Roman naturalist; for the sect alluded to did not arise until the third century BC, roughly 200 years after the time of Acron. Some scholars consider that the sect of the Empirici, in order to boast of a greater antiquity than the Dogmatics (founded by Thessalus, the son, and Polybus, the son-in-law, of Hippocrates, about 400 BC), merely claimed Acron as their founder.
None of Acron's works are now extant, though he wrote several in the Doric dialect on medical and physical subjects, of which the titles are preserved by the Suda and Eudocia. | Acron
Acron, son of Xenon, was an eminent Greek physician born at Agrigentum. His exact date is not known; but, as he is mentioned as being contemporary with Empedocles, who died about the beginning of the Peloponnesian war, he must have lived in the fifth century BC. From Sicily he went to Athens, and there opened a philosophical school (Template:Polytonic).
It is said that he was in that city during the great plague (430 BC), and that large fires for the purpose of purifying the air were kindled in the streets by his direction, which proved of great service to several of the sick.[1][2][3][4] It should however be borne in mind that there is no mention of this in Thucydides,[5] and, if it is true that Empedocles or Simonides (who died in 467 BC) wrote the epitaph on Acron, it may be doubted whether he was in Athens at all during the plague.
On his return to his native country, the physician asked the senate for a spot of ground where he might build a family tomb. The request was refused at the suggestion of Empedocles, who conceived that such a grant for such a purpose would interfere with the principle of equality he was anxious to establish at Agrigentum. As the sarcastic epitaph on Acron is probably the most complete jeu de mots on record, and therefore defies all translation, it will be given in Greek to preserve the paronomasia of the original:
The second line was sometimes read thus:
Some persons attributed the whole epigram to Simonides.[6][7][8]
Pliny considers him as the first of the Empirics.[9] But this has been considered an error on the part of the Roman naturalist; for the sect alluded to did not arise until the third century BC, roughly 200 years after the time of Acron. Some scholars consider that the sect of the Empirici, in order to boast of a greater antiquity than the Dogmatics (founded by Thessalus, the son, and Polybus, the son-in-law, of Hippocrates, about 400 BC), merely claimed Acron as their founder.[10]
None of Acron's works are now extant, though he wrote several in the Doric dialect on medical and physical subjects, of which the titles are preserved by the Suda and Eudocia.[11] | https://www.wikidoc.org/index.php/Acron | |
a94e76b449174027bd076b27ac8da6dcf80f4def | wikidoc | Actin | Actin
Actin is a globular, roughly 42-kDa protein found in all eukaryotic cells (except for nematode sperm) where it may be present at concentrations of over 100 μM. It is also one of the most highly-conserved proteins, differing by no more than 20% in species as diverse as algae and humans. It is the monomeric subunit of microfilaments, one of the three major components of the cytoskeleton, and of thin filaments, which are part of the contractile apparatus in muscle cells. Thus, actin participates in many important cellular functions, including muscle contraction, cell motility, cell division and cytokinesis, vesicle and organelle movement, cell signaling, and the establishment and maintenance of cell junctions and cell shape.
# Formation of thin filament
# Genetics
Principal interactions of structural proteins at cadherin-based adherens junction. Actin filaments are linked to α-actinin and to membrane through vinculin. The head domain of vinculin associates to E-cadherin via α-, β-, and γ-catenins. The tail domain of vinculin binds to membrane lipids and to actin filaments.
The protein actin is one of the most highly conserved throughout evolution because it interacts with a large number of other proteins, with 80.2% sequence conservation at the gene level between Homo sapiens and Saccharomyces cerevisiae (a species of yeast), and 95% conservation of the primary structure of the protein product.
Although most yeasts have only a single actin gene, higher eukaryotes, in general, express several isoforms of actin encoded by a family of related genes. Mammals have at least six actin isoforms coded by separate genes, which are divided into three classes (alpha, beta and gamma) according to their isoelectric point. In general, alpha actins are found in muscle (α-skeletal, α-aortic smooth, α-cardiac, and γ2-enteric smooth), whereas beta and gamma isoforms are prominent in non-muscle cells (β- and γ1-cytoplasmic). Although the amino acid sequences and in vitro properties of the isoforms are highly similar, these isoforms cannot completely substitute for one another in vivo.
The typical actin gene has an approximately 100-nucleotide 5' UTR, a 1200-nucleotide translated region, and a 200-nucleotide 3' UTR. The majority of actin genes are interrupted by introns, with up to 6 introns in any of 19 well-characterised locations. The high conservation of the family makes actin the favoured model for studies comparing the introns-early and introns-late models of intron evolution.
All non-spherical prokaryotes appear to possess genes such as MreB, which encode homologues of actin; these genes are required for the cell's shape to be maintained. The plasmid-derived gene ParM encodes an actin-like protein whose polymerised form is dynamically unstable, and appears to partition the plasmid DNA into the daughter cells during cell division by a mechanism analogous to that employed by microtubules in eukaryotic mitosis.
Actin is found in both smooth and rough endoplasmic reticulums.
# Functions
Actin has three main functions in cells :
- To form the most dynamic one of the three subclasses of the cytoskeleton, which gives mechanical support to cells, and hardwires the cytoplasm with the surroundings to support signal transduction.
- To allow cell motility (see Actoclampin molecular motors).
- In muscle cells as well as non-muscle cells, to generate force together with myosin proteins to support muscle contraction, vesicle movement, and other transport processes.
## Microfilaments
Individual subunits of actin are known as globular actin (G-actin). G-actin subunits assemble into long filamentous polymers called F-actin. Two parallel F-actin strands twist around each other in a helical formation, giving rise to microfilaments of the cytoskeleton. Microfilaments measure approximately 7 nm in diameter with a loop of the helix repeating every 37 nm.
### Polarity
The polarity of an actin filament can be determined by decorating the microfilament with myosin "S1" fragments, creating barbed (+) and pointed (-) ends on the filament. An S1 fragment is composed of the head and neck domains of myosin II.
## Actomyosin filaments
In muscle, actin is the major component of thin filaments, which, together with the motor protein myosin (which forms thick filaments), are arranged into actomyosin myofibrils. These fibrils comprise the mechanism of muscle contraction. Using the hydrolysis of ATP for energy, myosin heads undergo a cycle during which they attach to thin filaments, exerting a tension, and then depending on the load, perform a power stroke that causes the thin filaments to slide past, shortening the muscle.
In contractile bundles, the actin-bundling protein alpha-actinin separates each thin filament by ~35 nm. This increase in distance allows thick filaments to fit in between and interact, enabling deformation or contraction. In deformation, one end of myosin is bound to the plasma membrane while the other end "walks" toward the plus end of the actin filament. This pulls the membrane into a different shape relative to the cell cortex. For contraction, the myosin molecule is usually bound to two separate filaments and both ends simultaneously "walk" toward their filament's plus end, sliding the actin filaments closer to each other. This results in the shortening, or contraction, of the actin bundle (but not the filament). This mechanism is responsible for muscle contraction and cytokinesis, the division of one cell into two.
Actin polymerization and depolymerization is necessary in chemotaxis and cytokinesis. Nucleating factors are necessary to stimulate actin polymerization. Also, Actin filaments themselves bind ATP, and hydrolysis of this ATP stimulates destabilization of the polymer.
# History
Actin was first observed experimentally in 1887 by W.D. Halliburton, who extracted a protein from muscle that 'coagulated' preparations of myosin, and that he dubbed "myosin-ferment." However, Halliburton was unable to further characterise his findings, and the discovery of actin is credited instead to Brúnó F. Straub, a young biochemist working in Albert Szent-Györgyi's laboratory at the Institute of Medical Chemistry at the University of Szeged, Hungary.
In 1942, Straub developed a novel technique for extracting muscle protein that allowed him to isolate substantial amounts of relatively-pure actin. Straub's method is essentially the same as that used in laboratories today. Szent-Gyorgyi had previously described the more viscous form of myosin produced by slow muscle extractions as 'activated' myosin, and, since Straub's protein produced the activating effect, it was dubbed actin. The hostilities of World War II meant that Szent-Gyorgyi and Straub were unable to publish the work in Western scientific journals; it became well-known in the West only in 1945, when it was published as a supplement to the Acta Physiologica Scandinavica.
Straub continued to work on actin and in 1950 reported that actin contains bound ATP and that, during polymerisation of the protein into microfilaments, the nucleotide is hydrolysed to ADP and inorganic phosphate (which remain bound in the microfilament). Straub suggested that the transformation of ATP-bound actin to ADP-bound actin played a role in muscular contraction. In fact, this is true only in smooth muscle, and was not supported through experimentation until 2001.
The crystal structure of G-actin was solved in 1990 by Kabsch and colleagues. In the same year a model for F-actin was proposed by Holmes and colleagues. The model was derived by fitting a helix of G-actin structures according to low-resolution fiber diffraction data from the filament. Several models of the filament have been proposed since. However there is still no high-resolution X-ray structure of F-actin.
The Listeria bacteria use the cellular machinery to move around inside the host cell, by inducing directed polymerisation of actin by the ActA transmembrane protein, thus pushing the bacterial cell around. | Actin
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Actin is a globular, roughly 42-kDa protein found in all eukaryotic cells (except for nematode sperm) where it may be present at concentrations of over 100 μM. It is also one of the most highly-conserved proteins, differing by no more than 20% in species as diverse as algae and humans. It is the monomeric subunit of microfilaments, one of the three major components of the cytoskeleton, and of thin filaments, which are part of the contractile apparatus in muscle cells. Thus, actin participates in many important cellular functions, including muscle contraction, cell motility, cell division and cytokinesis, vesicle and organelle movement, cell signaling, and the establishment and maintenance of cell junctions and cell shape.
# Formation of thin filament
# Genetics
Principal interactions of structural proteins at cadherin-based adherens junction. Actin filaments are linked to α-actinin and to membrane through vinculin. The head domain of vinculin associates to E-cadherin via α-, β-, and γ-catenins. The tail domain of vinculin binds to membrane lipids and to actin filaments.
The protein actin is one of the most highly conserved throughout evolution because it interacts with a large number of other proteins, with 80.2% sequence conservation at the gene level between Homo sapiens and Saccharomyces cerevisiae (a species of yeast), and 95% conservation of the primary structure of the protein product.
Although most yeasts have only a single actin gene, higher eukaryotes, in general, express several isoforms of actin encoded by a family of related genes. Mammals have at least six actin isoforms coded by separate genes,[1] which are divided into three classes (alpha, beta and gamma) according to their isoelectric point. In general, alpha actins are found in muscle (α-skeletal, α-aortic smooth, α-cardiac, and γ2-enteric smooth), whereas beta and gamma isoforms are prominent in non-muscle cells (β- and γ1-cytoplasmic). Although the amino acid sequences and in vitro properties of the isoforms are highly similar, these isoforms cannot completely substitute for one another in vivo.[2]
The typical actin gene has an approximately 100-nucleotide 5' UTR, a 1200-nucleotide translated region, and a 200-nucleotide 3' UTR. The majority of actin genes are interrupted by introns, with up to 6 introns in any of 19 well-characterised locations. The high conservation of the family makes actin the favoured model for studies comparing the introns-early and introns-late models of intron evolution.
All non-spherical prokaryotes appear to possess genes such as MreB, which encode homologues of actin; these genes are required for the cell's shape to be maintained. The plasmid-derived gene ParM encodes an actin-like protein whose polymerised form is dynamically unstable, and appears to partition the plasmid DNA into the daughter cells during cell division by a mechanism analogous to that employed by microtubules in eukaryotic mitosis.[3]
Actin is found in both smooth and rough endoplasmic reticulums.
# Functions
Actin has three main functions in cells :
- To form the most dynamic one of the three subclasses of the cytoskeleton, which gives mechanical support to cells, and hardwires the cytoplasm with the surroundings to support signal transduction.
- To allow cell motility (see Actoclampin molecular motors).
- In muscle cells as well as non-muscle cells, to generate force together with myosin proteins to support muscle contraction, vesicle movement, and other transport processes.
## Microfilaments
Individual subunits of actin are known as globular actin (G-actin). G-actin subunits assemble into long filamentous polymers called F-actin. Two parallel F-actin strands twist around each other in a helical formation, giving rise to microfilaments of the cytoskeleton. Microfilaments measure approximately 7 nm in diameter with a loop of the helix repeating every 37 nm.
### Polarity
The polarity of an actin filament can be determined by decorating the microfilament with myosin "S1" fragments, creating barbed (+) and pointed (-) ends on the filament. An S1 fragment is composed of the head and neck domains of myosin II.
## Actomyosin filaments
In muscle, actin is the major component of thin filaments, which, together with the motor protein myosin (which forms thick filaments), are arranged into actomyosin myofibrils. These fibrils comprise the mechanism of muscle contraction. Using the hydrolysis of ATP for energy, myosin heads undergo a cycle during which they attach to thin filaments, exerting a tension, and then depending on the load, perform a power stroke that causes the thin filaments to slide past, shortening the muscle.
In contractile bundles, the actin-bundling protein alpha-actinin separates each thin filament by ~35 nm. This increase in distance allows thick filaments to fit in between and interact, enabling deformation or contraction. In deformation, one end of myosin is bound to the plasma membrane while the other end "walks" toward the plus end of the actin filament. This pulls the membrane into a different shape relative to the cell cortex. For contraction, the myosin molecule is usually bound to two separate filaments and both ends simultaneously "walk" toward their filament's plus end, sliding the actin filaments closer to each other. This results in the shortening, or contraction, of the actin bundle (but not the filament). This mechanism is responsible for muscle contraction and cytokinesis, the division of one cell into two.
Actin polymerization and depolymerization is necessary in chemotaxis and cytokinesis. Nucleating factors are necessary to stimulate actin polymerization. Also, Actin filaments themselves bind ATP, and hydrolysis of this ATP stimulates destabilization of the polymer.
# History
Actin was first observed experimentally in 1887 by W.D. Halliburton, who extracted a protein from muscle that 'coagulated' preparations of myosin, and that he dubbed "myosin-ferment."[4] However, Halliburton was unable to further characterise his findings, and the discovery of actin is credited instead to Brúnó F. Straub, a young biochemist working in Albert Szent-Györgyi's laboratory at the Institute of Medical Chemistry at the University of Szeged, Hungary.
In 1942, Straub developed a novel technique for extracting muscle protein that allowed him to isolate substantial amounts of relatively-pure actin. Straub's method is essentially the same as that used in laboratories today. Szent-Gyorgyi had previously described the more viscous form of myosin produced by slow muscle extractions as 'activated' myosin, and, since Straub's protein produced the activating effect, it was dubbed actin. The hostilities of World War II meant that Szent-Gyorgyi and Straub were unable to publish the work in Western scientific journals; it became well-known in the West only in 1945, when it was published as a supplement to the Acta Physiologica Scandinavica.[5]
Straub continued to work on actin and in 1950 reported that actin contains bound ATP [6] and that, during polymerisation of the protein into microfilaments, the nucleotide is hydrolysed to ADP and inorganic phosphate (which remain bound in the microfilament). Straub suggested that the transformation of ATP-bound actin to ADP-bound actin played a role in muscular contraction. In fact, this is true only in smooth muscle, and was not supported through experimentation until 2001.[7]
The crystal structure of G-actin was solved in 1990 by Kabsch and colleagues.[8] In the same year a model for F-actin was proposed by Holmes and colleagues.[9] The model was derived by fitting a helix of G-actin structures according to low-resolution fiber diffraction data from the filament. Several models of the filament have been proposed since. However there is still no high-resolution X-ray structure of F-actin.
The Listeria bacteria use the cellular machinery to move around inside the host cell, by inducing directed polymerisation of actin by the ActA transmembrane protein, thus pushing the bacterial cell around. | https://www.wikidoc.org/index.php/Actin | |
6274934cc9e164c3ad28fc06216f60de6bd3d461 | wikidoc | Actiq | Actiq
Actiq by Cephalon, is a solid formulation of fentanyl citrate on a plastic stick that dissolves slowly in the mouth for absorption across the buccal mucosa. Generically Actiq is a form of oral transmucosal fentanyl citrate (OTFC). In the UK, Fentanyl is a Class A drug under the Misuse of Drugs Act 1971. In the Netherlands, Fentanyl is a List I substance of the Opium Law. In the US, Fentanyl is a Schedule II controlled substance per the Controlled Substance Act. Other pharmaceutical preparations consisting of fentanyl are Durogesic and Duragesic (72 hour continuous-release fentanyl patches) and Fentora, a rapidly dissolving fentanyl lozenge which, like Actiq, is administered transmucosally over the buccal mucosa. OTFC is absorbed much like how nicotine is absorbed when dip is placed in one's mouth between the gum and cheek.
# Administration
Around 100 times stronger than morphine, Actiq is intended for opiate-tolerant individuals and is effective in treating cancer breakthrough pain. However, it is often prescribed for "off-label uses", i.e. not for cancer patients, such as bone injuries, migraines, severe back pain, cluster headaches, neuropathy, arthritis, and other situations of moderate to severe chronic, non-malignant pain.
The Actiq dosage unit is a white, berry-flavored lozenge on a stick which is swabbed on the buccal mucosa, between cheek and gum to release the fentanyl quickly into the bloodstream. It is most effective when the lozenge is consumed in exactly 15 minutes, as the balance of the drug absorbed through the cheeks and the amount swallowed is maintained.
# Absorption
Normally 25% of the drug is absorbed via the buccal mucosa directly into the bloodstream while the remaining 75% is swallowed and then slowly absorbed in the gastrointestinal tract. Two-thirds of the swallowed Actiq (or 50% of the total dose) is metabolized by the liver and becomes unavailable for any pain relief function, leaving only around 33% of the ingested fentanyl available for pain relief. This is why the drug is far less potent if consumed orally compared to transmucosally.
# Dosing
Actiq is available in 6 dosages, measured in micrograms: 200, 400, 600, 800, 1200, & 1600 mcg. Each dosage strength has its own color box and plastic handle:
Actiq 200 mcg--gray
Actiq 400 mcg--blue
Actiq 600 mcg--orange
Actiq 800 mcg--purple
Actiq 1200 mcg--green
Actiq 1600 mcg--burgundy
# Side-effects
Actiq, like all opioids, has a potential for abuse and can be habit forming. Actiq should not be taken with alcohol. Although Actiq was only approved by the FDA for treatment of intractable pain in cancer patients, it has been estimated that in the first half of 2006 approximately 90-99% of the 187,076 Actiq prescriptions filled in the U.S. were for "off-label uses", i.e. not for cancer patients., Actiq was reported to be one of many legally prescribed addictive medications found in Anna Nicole Smith's room when she died.
As with all opioids, there have also been reports of illicit use on the street, where it is (incorrectly) known as "morphine lollypops", and in the US as "perc-a-pop", and sells for between $5-25, depending on its dose. The attorneys-general of Connecticut and Pennsylvania have launched investigations into its diversion from the legitimate pharmaceutical market, including Cephalon's "sales and promotional practices for Provigil, Actiq and Gabitril". In order to curb misuse, many health insurers have begun to require precertification and/or quantity limits for Actiq prescriptions. ,,
An Actiq lozenge contains 2 grams of sugar (8 calories), making weight gain and tooth decay a conceivable concern for patients who consume many Actiqs per day. Diabetics also need to take Actiq's sugar content into account. A sugar-free version, called Actiq-SF, is in development, and should be available beginning first quarter 2007. Side effects include the normal side effects found with this class of narcotic analgesic plus constipation and dry mouth. Other side effects include rash, sweating, hot flashes, and dizziness.
# Generic Alternatives
Beginning late September, 2006, a generic version of Actiq has been available, made by Barr Pharmaceuticals. Cephalon has begun marketing its own version of generic Actiq to compete in the generic OTFC market. The generic versions of Actiq, simply called "oral transmucosal fentanyl citrate," are packaged just like name brand Actiq, and there is no difference in appearance, active and inactive ingredients, or function as compared to the name brand Actiq. Because Actiq is extremely expensive, the generic OTFC just hitting the market will likely make the drug more accessible. | Actiq
Actiq by Cephalon, is a solid formulation of fentanyl citrate on a plastic stick that dissolves slowly in the mouth for absorption across the buccal mucosa. Generically Actiq is a form of oral transmucosal fentanyl citrate (OTFC). In the UK, Fentanyl is a Class A drug under the Misuse of Drugs Act 1971. In the Netherlands, Fentanyl is a List I substance of the Opium Law. In the US, Fentanyl is a Schedule II controlled substance per the Controlled Substance Act. Other pharmaceutical preparations consisting of fentanyl are Durogesic and Duragesic (72 hour continuous-release fentanyl patches) and Fentora, a rapidly dissolving fentanyl lozenge which, like Actiq, is administered transmucosally over the buccal mucosa. OTFC is absorbed much like how nicotine is absorbed when dip is placed in one's mouth between the gum and cheek.
# Administration
Around 100 times stronger than morphine[1], Actiq is intended for opiate-tolerant individuals and is effective in treating cancer breakthrough pain. However, it is often prescribed for "off-label uses", i.e. not for cancer patients, such as bone injuries, migraines, severe back pain, cluster headaches, neuropathy, arthritis, and other situations of moderate to severe chronic, non-malignant pain. [1] [2] [3]
The Actiq dosage unit is a white, berry-flavored lozenge on a stick which is swabbed on the buccal mucosa, between cheek and gum to release the fentanyl quickly into the bloodstream. It is most effective when the lozenge is consumed in exactly 15 minutes, as the balance of the drug absorbed through the cheeks and the amount swallowed is maintained.
# Absorption
Normally 25% of the drug is absorbed via the buccal mucosa directly into the bloodstream while the remaining 75% is swallowed and then slowly absorbed in the gastrointestinal tract. Two-thirds of the swallowed Actiq (or 50% of the total dose) is metabolized by the liver and becomes unavailable for any pain relief function, leaving only around 33% of the ingested fentanyl available for pain relief. This is why the drug is far less potent if consumed orally compared to transmucosally.
# Dosing
Actiq is available in 6 dosages, measured in micrograms: 200, 400, 600, 800, 1200, & 1600 mcg. Each dosage strength has its own color box and plastic handle:
Actiq 200 mcg--gray
Actiq 400 mcg--blue
Actiq 600 mcg--orange
Actiq 800 mcg--purple
Actiq 1200 mcg--green
Actiq 1600 mcg--burgundy
# Side-effects
Actiq, like all opioids, has a potential for abuse and can be habit forming. Actiq should not be taken with alcohol. Although Actiq was only approved by the FDA for treatment of intractable pain in cancer patients, it has been estimated that in the first half of 2006 approximately 90-99% of the 187,076 Actiq prescriptions filled in the U.S. were for "off-label uses", i.e. not for cancer patients.[1], [2] Actiq was reported to be one of many legally prescribed addictive medications found in Anna Nicole Smith's room when she died.[1]
As with all opioids, there have also been reports of illicit use on the street, where it is (incorrectly) known as "morphine lollypops", and in the US as "perc-a-pop", and sells for between $5-25, depending on its dose.[4] The attorneys-general of Connecticut and Pennsylvania have launched investigations into its diversion from the legitimate pharmaceutical market, including Cephalon's "sales and promotional practices for Provigil, Actiq and Gabitril".[4] In order to curb misuse, many health insurers have begun to require precertification and/or quantity limits for Actiq prescriptions. [5],[6],[7]
An Actiq lozenge contains 2 grams of sugar [8] (8 calories), making weight gain and tooth decay a conceivable concern for patients who consume many Actiqs per day.[3] Diabetics also need to take Actiq's sugar content into account. A sugar-free version, called Actiq-SF, is in development, and should be available beginning first quarter 2007. Side effects include the normal side effects found with this class of narcotic analgesic plus constipation and dry mouth. Other side effects include rash, sweating, hot flashes, and dizziness.
# Generic Alternatives
Beginning late September, 2006, a generic version of Actiq has been available, made by Barr Pharmaceuticals. Cephalon has begun marketing its own version of generic Actiq to compete in the generic OTFC market. The generic versions of Actiq, simply called "oral transmucosal fentanyl citrate," are packaged just like name brand Actiq, and there is no difference in appearance, active and inactive ingredients, or function as compared to the name brand Actiq. Because Actiq is extremely expensive, the generic OTFC just hitting the market will likely make the drug more accessible. | https://www.wikidoc.org/index.php/Actiq | |
91cc8b02eeba86c770d8471ff3d79780b793ffc4 | wikidoc | Adult | Adult
The term adult describes any mature organism, but normally it refers to a human: one that is no longer a child / minor and is now either a man or a woman. Adulthood can be defined in terms of biology, psychological adult development, law, personal character, or social status. These different aspects of adulthood are often inconsistent and contradictory. A person may be biologically an adult, and have adult behavioral characteristics but still be treated as a child if they are under the legal age of majority. Conversely one may legally be an adult but possess none of the maturity and responsibility that define adult character.
Coming of age is the event; passing a series of tests to demonstrate the child is prepared for adulthood; or reaching a specified age, sometimes in conjunction with demonstrating preparation. Most modern societies determine legal adulthood based on reaching a legally-specified age without requiring a demonstration of physical maturity or preparation for adulthood.
"Adult" also means "not considered suitable for children," in particular as a euphemism for being related to sexual behaviour, such as adult entertainment, adult video, adult magazine, adult bookstore. However, adult education simply means education for adults, not particularly sex education.
# Biological adulthood
Adulthood is generally understood as the time when physical maturation is complete. One reaches their maximum height and secondary sex characteristics form such as body hair and facial hair, voice lowers in pitch (especially noticeable in men), and menses begin (women). Natural sleep patterns change in adulthood, as adults typically require less sleep than during adolescence. One thing people don't specify is what (psychologically) an adult is. A common theory is that adulthood is the real test of life, to experience the world from a first-person standpoint instead of through the parents. Then the adult can pass those experiences down to younger people and they can experience them when they grow up.
# Legal adulthood
Legally it means that one can engage in a contract. The same or a different minimum age may be applicable to, for example, parents losing parenting rights and duties regarding the person concerned, parents losing financial responsibility, marriage, voting, having a job, being a soldier, buying/possessing firearms (if legal at all), driving, traveling abroad, involvement with alcoholic beverages (if legal at all), smoking, sex, gambling (both lottery and casino) being a prostitute or a client of a prostitute (if legal at all), being a model or actor in pornography, etc. Admission of a young person to a place may be restricted because of danger for that person, and/or because of the risk that the young person causes damage (for example, at an exhibition of fragile items).
One can distinguish the legality of acts of a young person, and of enabling a young person to carry out that act, by selling, renting out, showing, permitting entrance, participating, etc. There may be distinction between commercially and socially enabling. Sometimes there is the requirement of supervision by a legal guardian, or just by an adult. Sometimes there is no requirement, but just a recommendation.
With regard to pornography one can distinguish:
- being allowed inside an adult establishment
- being allowed to purchase pornography
- being allowed to possess pornography
- another person being allowed to sell, rent out, or show the young person pornography, see disseminating pornography to a minor
- being a model or actor in pornography: rules for the young person, and for other people, regarding production, possession, etc. (see child pornography)
With regard to films with violence, etc.:
- another person being allowed to sell, rent out, or show the young person the film, a cinema being allowed to let the young person (under 18) enter
The legal definition of entering adulthood usually varies between ages 15–21, depending on the region in question. Some cultures in Africa define adult at age 13.
According to Jewish tradition, adulthood is reached at age 13 (the age of the Bar Mitzvah), for Jewish boys, for example, were expected to demonstrate preparation for adulthood by learning the Torah and other Jewish practices. The Christian Bible and Jewish scripture has no age requirement for adulthood or marrying, which includes engaging in sexual activity. According to The Disappearance of Childhood by Neil Postman, the Christian Church of the Middle Ages considered the age of accountability, when a person could be tried and even executed as an adult, to be age 7.
In most of the world, including the United States, the United Kingdom, and China, the legal adult age is 18, with some exceptions:
In Britain society expects people to be adults when they are only 16 even though they are not adults until they are 20.
# Personal characteristics
There are some qualities that symbolize adultness in most cultures. Not always is there a concordance between the qualities and the physical age of the person.
The adult character comprises:
- Self-control - restraint, emotional control.
- Stability - stable personality, strength.
- Independence - ability to self-regulate.
- Seriousness - ability to deal with life in a serious manner.
- Responsibility - accountability, commitment and reliability.
- Method/Tact - ability to think ahead and plan for the future, patience.
- Endurance - ability and willingness to cope with difficulties that present themselves.
- Experience - breadth of mind, understanding.
- Objectivity - perspective and realism.
# Social status
Adults, as a class, especially middle-age adults, enjoy an elevated status in society. This so-called “Adult Privilege” works in the same way as “White Privilege” by conferring often unspoken advantages, exemptions or immunities to members of the class; it also takes the form of adultism, which is a predisposition towards adults, inherently biased against children, youth, and all young people who aren't addressed or viewed as adults. For example, while society fixates on the supposedly immoral and destructive behavior of youth, adults are not held accountable when they often display the same if not worse behavior in certain areas such as drug abuse, obesity and crime. Ironically the status we afford adults for their maturity includes the privilege to act immaturely.
With such apparent double standards, some social critics have defined adulthood as an “organization” or “institution” that believes “they should always have the right to command and be obeyed.” | Adult
Template:Cleanup-restructure
The term adult describes any mature organism, but normally it refers to a human: one that is no longer a child / minor and is now either a man or a woman. Adulthood can be defined in terms of biology, psychological adult development, law, personal character, or social status. These different aspects of adulthood are often inconsistent and contradictory. A person may be biologically an adult, and have adult behavioral characteristics but still be treated as a child if they are under the legal age of majority. Conversely one may legally be an adult but possess none of the maturity and responsibility that define adult character.
Coming of age is the event; passing a series of tests to demonstrate the child is prepared for adulthood; or reaching a specified age, sometimes in conjunction with demonstrating preparation. Most modern societies determine legal adulthood based on reaching a legally-specified age without requiring a demonstration of physical maturity or preparation for adulthood.
"Adult" also means "not considered suitable for children," in particular as a euphemism for being related to sexual behaviour, such as adult entertainment, adult video, adult magazine, adult bookstore. However, adult education simply means education for adults, not particularly sex education.
# Biological adulthood
Adulthood is generally understood as the time when physical maturation is complete. One reaches their maximum height and secondary sex characteristics form such as body hair and facial hair, voice lowers in pitch (especially noticeable in men), and menses begin (women). Natural sleep patterns change in adulthood, as adults typically require less sleep than during adolescence. One thing people don't specify is what (psychologically) an adult is. A common theory is that adulthood is the real test of life, to experience the world from a first-person standpoint instead of through the parents. Then the adult can pass those experiences down to younger people and they can experience them when they grow up.
# Legal adulthood
Legally it means that one can engage in a contract. The same or a different minimum age may be applicable to, for example, parents losing parenting rights and duties regarding the person concerned, parents losing financial responsibility, marriage, voting, having a job, being a soldier, buying/possessing firearms (if legal at all), driving, traveling abroad, involvement with alcoholic beverages (if legal at all), smoking, sex, gambling (both lottery and casino) being a prostitute or a client of a prostitute (if legal at all), being a model or actor in pornography, etc. Admission of a young person to a place may be restricted because of danger for that person, and/or because of the risk that the young person causes damage (for example, at an exhibition of fragile items).
One can distinguish the legality of acts of a young person, and of enabling a young person to carry out that act, by selling, renting out, showing, permitting entrance, participating, etc. There may be distinction between commercially and socially enabling. Sometimes there is the requirement of supervision by a legal guardian, or just by an adult. Sometimes there is no requirement, but just a recommendation.
With regard to pornography one can distinguish:
- being allowed inside an adult establishment
- being allowed to purchase pornography
- being allowed to possess pornography
- another person being allowed to sell, rent out, or show the young person pornography, see disseminating pornography to a minor
- being a model or actor in pornography: rules for the young person, and for other people, regarding production, possession, etc. (see child pornography)
With regard to films with violence, etc.:
- another person being allowed to sell, rent out, or show the young person the film, a cinema being allowed to let the young person (under 18) enter
The legal definition of entering adulthood usually varies between ages 15–21, depending on the region in question. Some cultures in Africa define adult at age 13.
According to Jewish tradition, adulthood is reached at age 13 (the age of the Bar Mitzvah), for Jewish boys, for example, were expected to demonstrate preparation for adulthood by learning the Torah and other Jewish practices. The Christian Bible and Jewish scripture has no age requirement for adulthood or marrying, which includes engaging in sexual activity. According to The Disappearance of Childhood by Neil Postman, the Christian Church of the Middle Ages considered the age of accountability, when a person could be tried and even executed as an adult, to be age 7.
In most of the world, including the United States, the United Kingdom, and China, the legal adult age is 18, with some exceptions:
In Britain society expects people to be adults when they are only 16 even though they are not adults until they are 20.
# Personal characteristics
There are some qualities that symbolize adultness in most cultures. Not always is there a concordance between the qualities and the physical age of the person.
The adult character comprises:
- Self-control - restraint, emotional control.
- Stability - stable personality, strength.
- Independence - ability to self-regulate.
- Seriousness - ability to deal with life in a serious manner.
- Responsibility - accountability, commitment and reliability.
- Method/Tact - ability to think ahead and plan for the future, patience.
- Endurance - ability and willingness to cope with difficulties that present themselves.
- Experience - breadth of mind, understanding.
- Objectivity - perspective and realism.
# Social status
Template:Unbalanced
Adults, as a class, especially middle-age adults, enjoy an elevated status in society. This so-called “Adult Privilege” works in the same way as “White Privilege” by conferring often unspoken advantages, exemptions or immunities to members of the class; it also takes the form of adultism, which is a predisposition towards adults, inherently biased against children, youth, and all young people who aren't addressed or viewed as adults. For example, while society fixates on the supposedly immoral and destructive behavior of youth, adults are not held accountable when they often display the same if not worse behavior in certain areas such as drug abuse,[1] obesity and crime.[2] Ironically the status we afford adults for their maturity includes the privilege to act immaturely.
With such apparent double standards, some social critics have defined adulthood as an “organization” or “institution” that believes “they should always have the right to command and be obeyed.”[3] | https://www.wikidoc.org/index.php/Adult | |
60b4b9f173d590a8e59100792c30007a5d1a285d | wikidoc | Agada | Agada
Agada is one of the eight branches into which medical pseudoscience is divided by the Hindus. Agada treats of the best antidotes to Poisons, or toxicology.
Agada Tantra is defined as a section of toxicology; practitioners claim to be able to deal with food poisoning, snakebites, dog bites, insect bites etc. The school of toxicology was founded and run by Kashyapa, also known as Vriddhakashyapa, another contemporary of Atreya Punarvasu. He lived in Taksashila, Pakistan. His text was called the Kashyapa Samhita. This, however, is a different book than the Kashyapa Samhita of pediatrics. This text is not available now but the references of this text are found mentioned in different commentaries. Some other texts written by Alambayana, Ushana, Saunaka, and Latyayana were known to exist. However except for references to them, the original texts are no longer available.
The traditional practice of toxicology is still practiced by different families of Vishavaidyas (poison doctors) who claim to be specialists in toxicology. In fact, their knowledge is quite limited (especially compared to the knowledge attributed to earlier ayurvedic physicians) but villages still use these practices to attempt to deal with poisonous bites. In ancient times, it was the job of Vishavaidyas to protect members of the royal families from being poisoned, as well to poison enemies of the kings. | Agada
Agada is one of the eight branches into which medical pseudoscience is divided by the Hindus. Agada treats of the best antidotes to Poisons, or toxicology.
Agada Tantra is defined as a section of toxicology; practitioners claim to be able to deal with food poisoning, snakebites, dog bites, insect bites etc. The school of toxicology was founded and run by Kashyapa, also known as Vriddhakashyapa, another contemporary of Atreya Punarvasu. He lived in Taksashila, Pakistan. His text was called the Kashyapa Samhita. This, however, is a different book than the Kashyapa Samhita of pediatrics. This text is not available now but the references of this text are found mentioned in different commentaries. Some other texts written by Alambayana, Ushana, Saunaka, and Latyayana were known to exist. However except for references to them, the original texts are no longer available.
The traditional practice of toxicology is still practiced by different families of Vishavaidyas (poison doctors) who claim to be specialists in toxicology. In fact, their knowledge is quite limited (especially compared to the knowledge attributed to earlier ayurvedic physicians) but villages still use these practices to attempt to deal with poisonous bites. In ancient times, it was the job of Vishavaidyas to protect members of the royal families from being poisoned, as well to poison enemies of the kings.
Template:WH
Template:WS | https://www.wikidoc.org/index.php/Agada | |
18e1eb6364766e858811a9130c2711178065a0b0 | wikidoc | Agave | Agave
Agave is the name of a succulent plant of a large botanical genus of the same name, belonging to the family Agavaceae.
# Description
Chiefly Mexican, they occur also in the southern and western United States and in central and tropical South America. The plants have a large rosette of thick fleshy leaves generally ending in a sharp point and with a spiny margin; the stout stem is usually short, the leaves apparently springing from the root. Along with plants from the related genus Yucca, various Agave species are popular ornamental plants.
Each rosette is monocarpic and grows slowly to flower only once. During flowering a tall stem or "mast" grows from the center of the leaf rosette and bears a large number of shortly tubular flowers. After development of fruit the original plant dies, but suckers are frequently produced from the base of the stem which become new plants.
It is a common misconception that Agaves are a cactus. Agaves are closely related to the lily and amaryllis families, and are not related to cacti.
Agave species are used as food plants by the larvae of some Lepidoptera species including Batrachedra striolata, which has been recorded on A shawii.
# Commonly grown species
The most commonly grown species include Agave americana, Agave angustifolia, Blue agave (Agave tequilana) and Agave attenuata.
## Agave americana
One of the most familiar species is Agave americana, a native of tropical America. Common names include Century Plant, Maguey (in Mexico), or American Aloe (it is not, however, closely related to the genus Aloe). The name "Century Plant" refers to the long time the plant takes to flower, although the number of years before flowering occurs depends on the vigor of the individual, the richness of the soil and the climate; during these years the plant is storing in its fleshy leaves the nourishment required for the effort of flowering.
Agave americana, century plant, was introduced into Europe about the middle of the 16th century and is now widely cultivated for its handsome appearance; in the variegated forms the leaf has a white or yellow marginal or central stripe from base to apex. As the leaves unfold from the center of the rosette the impression of the marginal spines is very conspicuous on the still erect younger leaves. The tequ plants are usually grown in tubs and put out in the summer months, but in the winter require protection from frost. They mature very slowly and die after flowering, but are easily propagated by the offsets from the base of the stem.
## Agave attenuata
A. attenuata is a native of central Mexico and is uncommon in its natural habitat. Unlike most species of Agave, A. attenuata has a curved flower spike from which it derives one of its numerous common names - the foxtail agave.
A. attenuata is also commonly grown as a garden plant. Unlike many agaves, A. attenuata has no teeth or terminal spines making it an ideal plant for areas adjacent to footpaths. Like all agaves, A. attenuata is a succulent and requires little water or maintenance once established .
# Uses
Four major parts of the agave are edible: the flowers, the leaves, the stalks or basal rosettes, and the sap (called aguamiel—honey water).(Davidson 1999)
- Each agave plant will produce several pounds of edible flowers during the summer.
- The leaves may be collected in winter and spring, when the plants are rich in sap, for eating.
- The stalks, which are ready during the summer, before the blossom, weigh several pounds each. Roasted, they are sweet, like molasses.
- During the development of the inflorescence there is a rush of sap to the base of the young flower stalk. In the case of A. americana and other species, this is used by the Mexicans to make their national beverage, pulque.
- The flower shoot is cut out and the sap collected and subsequently fermented. By distillation, a spirit called mezcal is prepared; one of the most well-known forms of mezcal is tequila. In 2001 the Mexican Government and European Union agreed the classification of tequila and its categories. 100% Blue Agave Tequila must be made from the Weber Blue Agave plant, to rigorous specifications and only in certain Mexican states.
- The leaves of several species yield fiber: for instance, Agave rigida var. sisalana, Sisal hemp, Agave decipiens, False Sisal Hemp. Agave americana is the source of pita fiber and is used as a fiber plant in Mexico, the West Indies and southern Europe.
- When dried and cut in slices, the flowering stem forms natural razor strops, and the expressed juice of the leaves will lather in water like soap.
- The Natives of Mexico used the agave to make pens, nails and needles, as well as string to sew and make weavings. In India the plant is extensively used for hedges along railroads.
- Agave syrup (also called agave nectar) is used as an alternative to sugar in cooking.
- When dried out, the stalks can be used to make didgeridoos.
# Ethnomedical Uses
- Leaf tea or tincture taken orally is used to treat constipation and excess gas. It is also used as a diuretic.
- Root tea or tincture is taken orally to treat arthritic joints.
# Warnings
- The juice from many species of agave can cause acute contact dermatitis. It will produce reddening and blistering lasting one to two weeks. Episodes of itching may recur up to a year thereafter, even though there is no longer a visible rash. Irritation is, in part, caused by calcium oxalate raphides. Dried parts of the plants can be handled with bare hands with little or no effect.
# Taxonomy
Agave is a genus within the family Agavaceae, which is currently placed within the order Asparagales. Agaves were once classified in Liliaceae, but most references now include them in their own family, Agavaceae. The genus Agave is divided into two subgenera: Agave and Littaea.
Agaves have long presented special difficulties for taxonomy; variations within a species may be considerable, and a number of named species are of unknown origin and may just be variants of original wild species.
Spanish and Portuguese explorers probably brought agave plants back to Europe with them, but the plants became popular in Europe during the 19th century when many types were imported by collectors. Some have been continuously propagated by offset since then, and do not consistently resemble any species known in the wild, although this may simply be due to the differences in growing conditions in Europe.
# Species
There are many species of Agave, see the List of Agave species. | Agave
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Agave is the name of a succulent plant of a large botanical genus of the same name, belonging to the family Agavaceae.
# Description
Chiefly Mexican, they occur also in the southern and western United States and in central and tropical South America. The plants have a large rosette of thick fleshy leaves generally ending in a sharp point and with a spiny margin; the stout stem is usually short, the leaves apparently springing from the root. Along with plants from the related genus Yucca, various Agave species are popular ornamental plants.
Each rosette is monocarpic and grows slowly to flower only once. During flowering a tall stem or "mast" grows from the center of the leaf rosette and bears a large number of shortly tubular flowers. After development of fruit the original plant dies, but suckers are frequently produced from the base of the stem which become new plants.
It is a common misconception that Agaves are a cactus. Agaves are closely related to the lily and amaryllis families, and are not related to cacti.
Agave species are used as food plants by the larvae of some Lepidoptera species including Batrachedra striolata, which has been recorded on A shawii.
# Commonly grown species
The most commonly grown species include Agave americana, Agave angustifolia, Blue agave (Agave tequilana) and Agave attenuata.
## Agave americana
One of the most familiar species is Agave americana, a native of tropical America. Common names include Century Plant, Maguey (in Mexico), or American Aloe (it is not, however, closely related to the genus Aloe). The name "Century Plant" refers to the long time the plant takes to flower, although the number of years before flowering occurs depends on the vigor of the individual, the richness of the soil and the climate; during these years the plant is storing in its fleshy leaves the nourishment required for the effort of flowering.
Agave americana, century plant, was introduced into Europe about the middle of the 16th century and is now widely cultivated for its handsome appearance; in the variegated forms the leaf has a white or yellow marginal or central stripe from base to apex. As the leaves unfold from the center of the rosette the impression of the marginal spines is very conspicuous on the still erect younger leaves. The tequ plants are usually grown in tubs and put out in the summer months, but in the winter require protection from frost. They mature very slowly and die after flowering, but are easily propagated by the offsets from the base of the stem.
## Agave attenuata
A. attenuata is a native of central Mexico and is uncommon in its natural habitat. Unlike most species of Agave, A. attenuata has a curved flower spike from which it derives one of its numerous common names - the foxtail agave.
A. attenuata is also commonly grown as a garden plant. Unlike many agaves, A. attenuata has no teeth or terminal spines making it an ideal plant for areas adjacent to footpaths. Like all agaves, A. attenuata is a succulent and requires little water or maintenance once established .
# Uses
Four major parts of the agave are edible: the flowers, the leaves, the stalks or basal rosettes, and the sap (called aguamiel—honey water).(Davidson 1999)
- Each agave plant will produce several pounds of edible flowers during the summer.
- The leaves may be collected in winter and spring, when the plants are rich in sap, for eating.
- The stalks, which are ready during the summer, before the blossom, weigh several pounds each. Roasted, they are sweet, like molasses.
- During the development of the inflorescence there is a rush of sap to the base of the young flower stalk. In the case of A. americana and other species, this is used by the Mexicans to make their national beverage, pulque.
- The flower shoot is cut out and the sap collected and subsequently fermented. By distillation, a spirit called mezcal is prepared; one of the most well-known forms of mezcal is tequila. In 2001 the Mexican Government and European Union agreed the classification of tequila and its categories. 100% Blue Agave Tequila must be made from the Weber Blue Agave plant, to rigorous specifications and only in certain Mexican states.
- The leaves of several species yield fiber: for instance, Agave rigida var. sisalana, Sisal hemp, Agave decipiens, False Sisal Hemp. Agave americana is the source of pita fiber and is used as a fiber plant in Mexico, the West Indies and southern Europe.
- When dried and cut in slices, the flowering stem forms natural razor strops, and the expressed juice of the leaves will lather in water like soap.
- The Natives of Mexico used the agave to make pens, nails and needles, as well as string to sew and make weavings. In India the plant is extensively used for hedges along railroads.
- Agave syrup (also called agave nectar) is used as an alternative to sugar in cooking.
- When dried out, the stalks can be used to make didgeridoos.
# Ethnomedical Uses
- Leaf tea or tincture taken orally is used to treat constipation and excess gas. It is also used as a diuretic.
- Root tea or tincture is taken orally to treat arthritic joints.
# Warnings
- The juice from many species of agave can cause acute contact dermatitis. It will produce reddening and blistering lasting one to two weeks. Episodes of itching may recur up to a year thereafter, even though there is no longer a visible rash. Irritation is, in part, caused by calcium oxalate raphides. Dried parts of the plants can be handled with bare hands with little or no effect.
# Taxonomy
Agave is a genus within the family Agavaceae, which is currently placed within the order Asparagales. Agaves were once classified in Liliaceae, but most references now include them in their own family, Agavaceae. The genus Agave is divided into two subgenera: Agave and Littaea.
Agaves have long presented special difficulties for taxonomy; variations within a species may be considerable, and a number of named species are of unknown origin and may just be variants of original wild species.
Spanish and Portuguese explorers probably brought agave plants back to Europe with them, but the plants became popular in Europe during the 19th century when many types were imported by collectors. Some have been continuously propagated by offset since then, and do not consistently resemble any species known in the wild, although this may simply be due to the differences in growing conditions in Europe.
# Species
There are many species of Agave, see the List of Agave species. | https://www.wikidoc.org/index.php/Agave | |
33bb0d7d70ac50dea1fb9d47b334c6cb23a51d80 | wikidoc | Agrin | Agrin
Agrin is a large proteoglycan whose best-characterised role is in the development of the neuromuscular junction during embryogenesis. Agrin is named based on its involvement in the aggregation of acetylcholine receptors during synaptogenesis. In humans, this protein is encoded by the AGRN gene.
This protein has nine domains homologous to protease inhibitors. It may also have functions in other tissues and during other stages of development. It is a major proteoglycan component in the glomerular basement membrane and may play a role in the renal filtration and cell-matrix interactions.
# Discovery
Agrin was first identified by the U.J. McMahan laboratory, Stanford University.
# Mechanism of action
During development in humans, the growing end of motor neuron axons secrete a protein called agrin.When secreted, agrin binds to several receptors on the surface of skeletal muscle. The receptor appears to be required for the formation of the neuromuscular junction (NMJ) is called the MuSK receptor (Muscle specific kinase). MuSK is a receptor tyrosine kinase - meaning that it induces cellular signaling by causing the addition of phosphate molecules to particular tyrosines on itself and on proteins that bind the cytoplasmic domain of the receptor.
In addition to MuSK, agrin binds several other proteins on the surface of muscle, including dystroglycan and laminin. It is seen that these additional binding steps are required to stabilize the NMJ.
The requirement for Agrin and MuSK in the formation of the NMJ was demonstrated primarily by knockout mouse studies. In mice that are deficient for either protein, the neuromuscular junction does not form. Many other proteins also comprise the NMJ, and are required to maintain its integrity. For example,
MuSK also binds a protein called "dishevelled" (Dvl), which is in the Wnt signalling pathway. Dvl is additionally required for MuSK-mediated clustering of AChRs, since inhibition of Dvl blocks clustering.
# Signaling
The nerve secretes agrin, resulting in phosphorylation of the MuSK receptor.
It seems that the MuSK receptor recruits casein kinase 2, which is required for clustering.
A protein called rapsyn is then recruited to the primary MuSK scaffold, to induce the additional clustering of acetylcholine receptors (AChR). This is thought of as the secondary scaffold. A protein called Dok-7 has shown to be additionally required for the formation of the secondary scaffold; it is apparently recruited after MuSK phosphorylation and before acetylcholine receptors are clustered.
# Structure
There are three potential heparan sulfate (HS) attachment sites within the primary structure of agrin, but it is thought that only two of these actually carry HS chains when the protein is expressed.
In fact, one study concluded that at least two attachment sites are necessary by inducing synthetic agents. Since agrin fragments induce acetylcholine receptor aggregation as well as phosphorylation of the MuSK receptor, researchers spliced them and found that the variant did not trigger phosphorylation. It has also been shown that the G3 domain of agrin is very plastic, meaning it can discriminate between binding partners for a better fit.
Heparan sulfate glycosaminoglycans covalently linked to the agrin protein have been shown to play a role in the clustering of AChR. Interference in the correct formation of heparan sulfate through the addition of chlorate to skeletal muscle cell culture results in a decrease in the frequency of spontaneous acetylcholine receptor (AChR) clustering. It may be that rather than solely binding directly to the agrin protein core a number of components of the secondary scaffold may also interact with its heparan sulfate side-chains.
A role in the retention of anionic macromolecules within the vasculature has also been suggested for agrin-linked HS at the glomerular or alveolar basement membrane. | Agrin
Agrin is a large proteoglycan whose best-characterised role is in the development of the neuromuscular junction during embryogenesis. Agrin is named based on its involvement in the aggregation of acetylcholine receptors during synaptogenesis. In humans, this protein is encoded by the AGRN gene.[1][2][3]
This protein has nine domains homologous to protease inhibitors.[4] It may also have functions in other tissues and during other stages of development. It is a major proteoglycan component in the glomerular basement membrane and may play a role in the renal filtration and cell-matrix interactions.[5]
# Discovery
Agrin was first identified by the U.J. McMahan laboratory, Stanford University.[6]
# Mechanism of action
During development in humans, the growing end of motor neuron axons secrete a protein called agrin.[7]When secreted, agrin binds to several receptors on the surface of skeletal muscle. The receptor appears to be required for the formation of the neuromuscular junction (NMJ) is called the MuSK receptor (Muscle specific kinase).[8][9] MuSK is a receptor tyrosine kinase - meaning that it induces cellular signaling by causing the addition of phosphate molecules to particular tyrosines on itself and on proteins that bind the cytoplasmic domain of the receptor.
In addition to MuSK, agrin binds several other proteins on the surface of muscle, including dystroglycan and laminin. It is seen that these additional binding steps are required to stabilize the NMJ.
The requirement for Agrin and MuSK in the formation of the NMJ was demonstrated primarily by knockout mouse studies. In mice that are deficient for either protein, the neuromuscular junction does not form.[10] Many other proteins also comprise the NMJ, and are required to maintain its integrity. For example,
MuSK also binds a protein called "dishevelled" (Dvl), which is in the Wnt signalling pathway. Dvl is additionally required for MuSK-mediated clustering of AChRs, since inhibition of Dvl blocks clustering.
# Signaling
The nerve secretes agrin, resulting in phosphorylation of the MuSK receptor.
It seems that the MuSK receptor recruits casein kinase 2, which is required for clustering.[11]
A protein called rapsyn is then recruited to the primary MuSK scaffold, to induce the additional clustering of acetylcholine receptors (AChR). This is thought of as the secondary scaffold. A protein called Dok-7 has shown to be additionally required for the formation of the secondary scaffold; it is apparently recruited after MuSK phosphorylation and before acetylcholine receptors are clustered.
# Structure
There are three potential heparan sulfate (HS) attachment sites within the primary structure of agrin, but it is thought that only two of these actually carry HS chains when the protein is expressed.
In fact, one study concluded that at least two attachment sites are necessary by inducing synthetic agents. Since agrin fragments induce acetylcholine receptor aggregation as well as phosphorylation of the MuSK receptor, researchers spliced them and found that the variant did not trigger phosphorylation. It has also been shown that the G3 domain of agrin is very plastic, meaning it can discriminate between binding partners for a better fit.[12]
Heparan sulfate glycosaminoglycans covalently linked to the agrin protein have been shown to play a role in the clustering of AChR. Interference in the correct formation of heparan sulfate through the addition of chlorate to skeletal muscle cell culture results in a decrease in the frequency of spontaneous acetylcholine receptor (AChR) clustering. It may be that rather than solely binding directly to the agrin protein core a number of components of the secondary scaffold may also interact with its heparan sulfate side-chains.[13]
A role in the retention of anionic macromolecules within the vasculature has also been suggested for agrin-linked HS at the glomerular or alveolar basement membrane. | https://www.wikidoc.org/index.php/Agrin | |
8aeddba59dff411e7f1feac8bf2833e65d81e6a8 | wikidoc | Alcon | Alcon
Alcon, (Template:Nyse) headquartered in Hünenberg, Switzerland, is a global medical company specializing in eye care products. Alcon's U.S. headquarters is located in Fort Worth, Texas.
# History
Alcon was founded in 1945 in Fort Worth, Texas, USA. The company started as a small pharmacy in Fort Worth and was named for its founders, pharmacists Robert Alexander and William Conner. Conner and Alexander focused on sterile ophthalmic products, which no other company specialized in at the time, and built their business by researching eyecare products that would reduce contamination and increase safety. Following incorporation in 1947, Alcon grew steadily to become a leader in their field.
Nestlé of Switzerland purchased Alcon in 1977. This was during a time of rapid growth for Nestlé and was their first venture into the pharmaceutical industry. Alcon expanded its manufacturing capability with new plants in South America and Europe and drastically increased its investment in research. In the 80s and 90s, Alcon continued to grow and became the largest and most profitable ophthalmic company in the world. The Alcon product line has expanded from pharmaceuticals to the surgical arena. The Acrysof intraocular lens implant is the most commonly used implant in cataract surgery worldwide. Today, Alcon has operations in 75 countries and their products are sold in over 180 countries. Alcon employs over 12,000 employees worldwide.
Alcon was spun off from Nestlé in 2002 and re-entered the NYSE with an IPO on March 21. Nestlé retains 75% of the stock.
# Consumer products
## Contact lens care
- Opti-Free RepleniSH Multi-Purpose Disinfecting Solution File:Alcon Opti Free Express.jpgA 12 OZ US retail bottle of Opti-Free Express No Rub Solution.
- Opti-Free Express No Rub Solution
- Opti-Free Supraclens Active Cleaner
- Unique-pH Multi-Purpose Solution (discontinued production on July 2007 )
- Clerz Plus Lens Drops
- PLIAGEL Cleaning Solution
- ALCON Saline Solution
- UNISOL 4 Saline Solution
## Dry eye
- Systane Lubricant Eye Drops
- Tears Naturale Forte Lubricant Eye Drops
- Tears Naturale Lubricant Eye Drops
- Tears Naturale II Lubricant Eye Drops
- Bion Tears Lubricant Eye Drops
- Poly-Tears Lubricating Eye Drops
## Other
- ICAPS Vitamins
- Naphcon-A Eye Allergy Drops
# Pharmaceutical products
## Glaucoma
- Azopt (brinzolamide)
- Betoptic (betaxolol)
- Betoptic S (betaxolol suspension)
- DuoTrav (travoprost/timolol)
- Iopidine (apraclonidine)
- Isopto Carbachol (carbachol)
- Isopto Carpine (pilocarpine)
- Travatan (travoprost)
- Travatan Z (travoprost)
## Ocular antibiotics
- Ciloxan (ciprofloxacin)
- TobraDex (tobramycin/dexamethasone)
- Tobrex (tobramycin)
- Vigamox (moxifloxacin)
## Ocular anti-inflammatory agents
- Flucon/Flarex (Fluorometholone)
- Maxidex (dexamethasone)
- Nevanac (nepafenac)
- Patanol (olopatadine)
- Vexol (rimexolone)
## Otic antibiotics
- Ciproxin HC/Cipro HC (ciprofloxacin/hydrocortisone)
- Ciprodex Otic (ciprofloxacin/dexamethasone)
- Econopred Plus (prednisolone acetate)
## Macular degeneration
- Retaane (anecortave)
# Surgical Products
- LADARVision (performs laser eye surgery)
LADAR-6000 surgical laser
- LADAR-6000 surgical laser
- INFINITI&tm; Vision System (performs phacoemulsification cataract surgery)
- Ophthalmic Viscosurgical Devices: | Alcon
Template:Infobox Company
Alcon, (Template:Nyse) headquartered in Hünenberg, Switzerland, is a global medical company specializing in eye care products. Alcon's U.S. headquarters is located in Fort Worth, Texas.
# History
Alcon was founded in 1945 in Fort Worth, Texas, USA. The company started as a small pharmacy in Fort Worth and was named for its founders, pharmacists Robert Alexander and William Conner. Conner and Alexander focused on sterile ophthalmic products, which no other company specialized in at the time, and built their business by researching eyecare products that would reduce contamination and increase safety. Following incorporation in 1947, Alcon grew steadily to become a leader in their field.
Nestlé of Switzerland purchased Alcon in 1977. This was during a time of rapid growth for Nestlé and was their first venture into the pharmaceutical industry. Alcon expanded its manufacturing capability with new plants in South America and Europe and drastically increased its investment in research. In the 80s and 90s, Alcon continued to grow and became the largest and most profitable ophthalmic company in the world. The Alcon product line has expanded from pharmaceuticals to the surgical arena. The Acrysof intraocular lens implant is the most commonly used implant in cataract surgery worldwide. Today, Alcon has operations in 75 countries and their products are sold in over 180 countries. Alcon employs over 12,000 employees worldwide.
Alcon was spun off from Nestlé in 2002 and re-entered the NYSE with an IPO on March 21. Nestlé retains 75% of the stock.
# Consumer products
## Contact lens care
- Opti-Free RepleniSH Multi-Purpose Disinfecting Solution File:Alcon Opti Free Express.jpgA 12 OZ US retail bottle of Opti-Free Express No Rub Solution.
- Opti-Free Express No Rub Solution
- Opti-Free Supraclens Active Cleaner
- Unique-pH Multi-Purpose Solution (discontinued production on July 2007 [1])
- Clerz Plus Lens Drops
- PLIAGEL Cleaning Solution
- ALCON Saline Solution
- UNISOL 4 Saline Solution
## Dry eye
- Systane Lubricant Eye Drops
- Tears Naturale Forte Lubricant Eye Drops
- Tears Naturale Lubricant Eye Drops
- Tears Naturale II Lubricant Eye Drops
- Bion Tears Lubricant Eye Drops
- Poly-Tears Lubricating Eye Drops
## Other
- ICAPS Vitamins
- Naphcon-A Eye Allergy Drops
# Pharmaceutical products
## Glaucoma
- Azopt (brinzolamide)
- Betoptic (betaxolol)
- Betoptic S (betaxolol suspension)
- DuoTrav (travoprost/timolol)
- Iopidine (apraclonidine)
- Isopto Carbachol (carbachol)
- Isopto Carpine (pilocarpine)
- Travatan (travoprost)
- Travatan Z (travoprost)
## Ocular antibiotics
- Ciloxan (ciprofloxacin)
- TobraDex (tobramycin/dexamethasone)
- Tobrex (tobramycin)
- Vigamox (moxifloxacin)
## Ocular anti-inflammatory agents
- Flucon/Flarex (Fluorometholone)
- Maxidex (dexamethasone)
- Nevanac (nepafenac)
- Patanol (olopatadine)
- Vexol (rimexolone)
## Otic antibiotics
- Ciproxin HC/Cipro HC (ciprofloxacin/hydrocortisone)
- Ciprodex Otic (ciprofloxacin/dexamethasone)
- Econopred Plus (prednisolone acetate)
## Macular degeneration
- Retaane (anecortave)
# Surgical Products
- LADARVision (performs laser eye surgery)
LADAR-6000 surgical laser
- LADAR-6000 surgical laser
- INFINITI&tm; Vision System (performs phacoemulsification cataract surgery)
- Ophthalmic Viscosurgical Devices: | https://www.wikidoc.org/index.php/Alcon | |
7d9cda6326f61146a1a5943c1831acd286fa67cb | wikidoc | CRYAB | CRYAB
Alpha-crystallin B chain is a protein that in humans is encoded by the CRYAB gene. It is part of the small heat shock protein family and functions as molecular chaperone that primarily binds misfolded proteins to prevent protein aggregation, as well as inhibit apoptosis and contribute to intracellular architecture. Post-translational modifications decrease the ability to chaperone. Defects in this gene/protein have been associated with cancer and neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease.
# Structure
Crystallins are separated into two classes: taxon-specific, or enzyme, and ubiquitous. The latter class constitutes the major proteins of vertebrate eye lens and maintains the transparency and refractive index of the lens. Since lens central fiber cells lose their nuclei during development, these crystallins are made and then retained throughout life, making them extremely stable proteins. Mammalian lens crystallins are divided into alpha, beta, and gamma families; beta and gamma crystallins are also considered as a superfamily. Alpha and beta families are further divided into acidic and basic groups.
Seven protein regions exist in crystallins: four homologous motifs, a connecting peptide, and N- and C-terminal extensions. Alpha crystallins are composed of two gene products: alpha-A and alpha-B, for acidic and basic, respectively. These heterogeneous aggregates consist of 30–40 subunits; the alpha-A and alpha-B subunits have a 3:1 ratio, respectively.
# Function
Alpha B chain crystallins (αBC) can be induced by heat shock, ischemia, and oxidation, and are members of the small heat shock protein (sHSP also known as the HSP20) family. They act as molecular chaperones although they do not renature proteins and release them in the fashion of a true chaperone; instead, they bind improperly folded proteins to prevent protein aggregation.
Furthermore, αBC may confer stress resistance to cells by inhibiting the processing of the pro-apoptotic protein caspase-3. Two additional functions of alpha crystallins are an autokinase activity and participation in the intracellular architecture. Alpha-A and alpha-B gene products are differentially expressed; alpha-A is preferentially restricted to the lens and alpha-B is expressed widely in many tissues and organs. Elevated expression of alpha-B crystallin occurs in many neurological diseases; a missense mutation cosegregated in a family with a desmin-related myopathy.
# Clinical significance
Although not yet clearly understood, defective chaperone activity is expected to trigger the accumulation of protein aggregates and underlie the development of α-crystallinopathy, or the failure of protein quality control, resulting in protein deposition diseases such as Alzheimer’s disease and Parkinson’s disease. Mutations in CRYAB could also cause restrictive cardiomyopathy.
ER-anchored αBC can suppress aggregate formation mediated by the disease mutant.Thus, modulation of the micromilieu surrounding the ER membrane can serve as a potential target in developing pharmacological interventions for protein deposition disease.
Though expressed highly in eye lens and muscle tissues, αBC can also be found in several types of cancer, among which head and neck squamous cell carcinoma (HNSCC) and breast carcinomas, as well as in patients with tuberous sclerosis. αBC expression is associated with metastasis formation in HNSCC and in breast carcinomas and in other types of cancer, expression is often correlated with poor prognosis as well. The expression of αBC can be increased during various stresses, like heat shock, osmotic stress or exposure to heavy metals, which then may lead to prolonged survival of cells under these conditions.
# Interactions
CRYAB has been shown to interact with:
- CRYAA,
- CRYBB2,
- CRYGC,
- HSPB2,
- Hsp27, and
- PSMA3. | CRYAB
Alpha-crystallin B chain is a protein that in humans is encoded by the CRYAB gene.[1] It is part of the small heat shock protein family and functions as molecular chaperone that primarily binds misfolded proteins to prevent protein aggregation, as well as inhibit apoptosis and contribute to intracellular architecture.[2][3][4] Post-translational modifications decrease the ability to chaperone.[2][4] Defects in this gene/protein have been associated with cancer and neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease.[2][3][4]
# Structure
Crystallins are separated into two classes: taxon-specific, or enzyme, and ubiquitous. The latter class constitutes the major proteins of vertebrate eye lens and maintains the transparency and refractive index of the lens. Since lens central fiber cells lose their nuclei during development, these crystallins are made and then retained throughout life, making them extremely stable proteins. Mammalian lens crystallins are divided into alpha, beta, and gamma families; beta and gamma crystallins are also considered as a superfamily. Alpha and beta families are further divided into acidic and basic groups.
Seven protein regions exist in crystallins: four homologous motifs, a connecting peptide, and N- and C-terminal extensions. Alpha crystallins are composed of two gene products: alpha-A and alpha-B, for acidic and basic, respectively. These heterogeneous aggregates consist of 30–40 subunits; the alpha-A and alpha-B subunits have a 3:1 ratio, respectively.[2]
# Function
Alpha B chain crystallins (αBC) can be induced by heat shock, ischemia, and oxidation, and are members of the small heat shock protein (sHSP also known as the HSP20) family.[2][5] They act as molecular chaperones although they do not renature proteins and release them in the fashion of a true chaperone; instead, they bind improperly folded proteins to prevent protein aggregation.[2][3][4]
Furthermore, αBC may confer stress resistance to cells by inhibiting the processing of the pro-apoptotic protein caspase-3.[4] Two additional functions of alpha crystallins are an autokinase activity and participation in the intracellular architecture. Alpha-A and alpha-B gene products are differentially expressed; alpha-A is preferentially restricted to the lens and alpha-B is expressed widely in many tissues and organs. Elevated expression of alpha-B crystallin occurs in many neurological diseases; a missense mutation cosegregated in a family with a desmin-related myopathy.[2]
# Clinical significance
Although not yet clearly understood, defective chaperone activity is expected to trigger the accumulation of protein aggregates and underlie the development of α-crystallinopathy, or the failure of protein quality control, resulting in protein deposition diseases such as Alzheimer’s disease and Parkinson’s disease. Mutations in CRYAB could also cause restrictive cardiomyopathy.[6]
ER-anchored αBC can suppress aggregate formation mediated by the disease mutant.Thus, modulation of the micromilieu surrounding the ER membrane can serve as a potential target in developing pharmacological interventions for protein deposition disease.[3]
Though expressed highly in eye lens and muscle tissues, αBC can also be found in several types of cancer, among which head and neck squamous cell carcinoma (HNSCC) and breast carcinomas, as well as in patients with tuberous sclerosis.[7] αBC expression is associated with metastasis formation in HNSCC and in breast carcinomas and in other types of cancer, expression is often correlated with poor prognosis as well.[8] The expression of αBC can be increased during various stresses, like heat shock, osmotic stress or exposure to heavy metals, which then may lead to prolonged survival of cells under these conditions.[4]
# Interactions
CRYAB has been shown to interact with:
- CRYAA,[9]
- CRYBB2,[9]
- CRYGC,[9]
- HSPB2,[10]
- Hsp27,[9][11] and
- PSMA3.[12] | https://www.wikidoc.org/index.php/Alfa-B-crystallin | |
ecdbb62d9f2cf27f5c46a19f3492d866842bc976 | wikidoc | Algae | Algae
# Overview
Algae have conventionally been regarded as simple plants within the study of botany. All are Eukaryota, though Chromophyta have Bacterial (see Blue-green algae) characteristics and some authorities consider them all to be Protists, however this view is now considered to be outdated. They may still be included in the algae as plants. Some authors often include the blue-green algae (Cyanophyta) but note that they are not eukaryote. Algae do not represent a single evolutionary direction or line but a level of organization that may have developed several times in the early history of life on Earth.
The protists are traditionally considered more animal-like (see Protozoa).
The prokaryotic forms, referred to as blue-green algae are only half-algae with a mixture of bacterial characteristics. However, they are quite distant from the bacteria and are referred to by some as Cyanochloronta. All other forms belong as true eukaryota algae within the study of Botany, they have a nucleus enclosed within a membrane. The protoctists are defined by some as eukaryotic microorganisms with the exception of animals and plants and including fungi and algae, slime moulds and other obscure eukaryotes. There is still some disagreement on some of these matters.
Algae range from single-cell organisms to multicellular organisms, some with fairly complex differentiated form and (if marine) called seaweeds. All lack leaves, roots, flowers, seeds and other organ structures that characterize higher plants (vascular plants). They are distinguished from other protozoa in that they are photoautotrophic although this is not a hard or vast distinction as some groups contain members that are mixotrophic, deriving energy both from photosynthesis and uptake of organic carbon either by osmotrophy, myzotrophy, or phagotrophy. Some unicellular species rely entirely on external energy sources and have reduced or lost their photosynthetic apparatus.
All algae have photosynthetic machinery ultimately derived from the cyanobacteria, and so produce oxygen as a byproduct of photosynthesis, unlike non-cyanobacterial photosynthetic bacteria. It is estimated that algae produce about 73 to 87 percent of the net global production of oxygen - which is available to humans and other animals for respiration.
# Ecology
Algae are usually found in damp places or bodies of water and thus are common in terrestrial as well as aquatic environments. However, terrestrial algae are usually rather inconspicuous and far more common in moist, tropical regions than dry ones, because algae lack vascular tissues and other adaptations to live on land. Algae can, however, endure dryness and other conditions in symbiosis with a fungus as lichen.
The various sorts of algae play significant roles in aquatic ecology. Microscopic forms that live suspended in the water column — called phytoplankton — provide the food base for most marine food chains. In very high densities (so-called algal blooms) these algae may discolor the water and outcompete or poison other life forms. Seaweeds grow mostly in shallow marine waters, however some have been recorded to a depth of 300 m.Some are used as human food or harvested for useful substances such as agar or fertilizer.
# Study of algae
The study of marine and freshwater algae is called phycology or algology.
The US Algal Collection is represented by almost 300,000 accessioned and inventoried herbarium specimens.
# Classification
## Prokaryotic algae
Cyanobacteria have been included among the algae, referred to as the cyanophytes or Blue-green algae, (the term "algae" refers to any aquatic organisms capable of photosynthesis) though some recent treatises on algae specifically exclude them. Cyanobacteria are some of the oldest organisms to appear in the fossil record dating back to the Precambrian, possibly as far as about 3.5 billion years. Ancient cyanobacteria likely produced much of the oxygen in the Earth's atmosphere.
Cyanobacteria can be unicellular, colonial, or filamentous. They have a prokaryotic cell structure typical of bacteria and conduct photosynthesis on specialized cytoplasmic membranes called thylakoid membranes, rather than in organelles. Some filamentous blue-green algae have specialized cells, termed heterocysts, in which nitrogen fixation occurs. the perfect prokaryotic cell consist of miscalgnous sheath covering cellwall that consistof pectinic substance and sachride while the cellwall consist of 4 layer outer and inner and middle layer while the fourth layer is attached to plasma membrane and the protoplast consist of 2 part peripheral coloured partknown by chromatoplasm which contain the pigments in case of algae and contain photothynsis producte.g in cyanobacteria it contain chlorophylla, b-caroteinand c-phycocyanin and c-phycoerthyrin
## Eukaryotic algae
All other algae are eukaryotes and conduct photosynthesis within membrane-bound structures (organelles) called chloroplasts. Chloroplasts contain DNA and are similar in structure to cyanobacteria, presumably representing reduced cyanobacterial endosymbionts. The exact nature of the chloroplasts is different among the different lines of algae, reflecting different endosymbiotic events. The table below lists the three major groups of eukaryotic algae and their lineage relationship is shown in the figure on the left. Note many of these groups contain some members that are no longer photosynthetic. Some retain plastids, but not chloroplasts, while others have lost them entirely.
It was W.H.Harvey (1811 — 1866) who first divided the algae into four divisions based on their pigmentation. This is the first use of a biochemical criterion in plant systematics. Harvey's four divisions were: red algae (Rhodophyta), brown algae (Heteromontophyta), green algae (Chlorophyta) and Diatomaceae (Dixon, 1973 p.232).
# Forms of algae
Most of the simpler algae are unicellular flagellates or amoeboids, but colonial and non-motile forms have developed independently among several of the groups. Some of the more common organizational levels, more than one of which may occur in the life cycle of a species, are
- Colonial: small, regular groups of motile cells
- Capsoid: individual non-motile cells embedded in mucilage
- Coccoid: individual non-motile cells with cell walls
- Palmelloid: non-motile cells embedded in mucilage
- Filamentous: a string of non-motile cells connected together, sometimes branching
- Parenchymatous: cells forming a thallus with partial differentiation of tissues
In three lines even higher levels of organization have been reached, imma hit with full tissue differentiation. These are the brown algae —some of which may reach 50 m in length (kelps)—the red algae , and the green algae . The most complex forms are found among the green algae (see Charales and Charophyta), in a lineage that eventually led to the higher land plants. The point where these non-algal plants begin and algae stop is usually taken to be the presence of reproductive organs with protective cell layers, a characteristic not found in the other alga groups.
The first plants on earth were algae and these still thrive in a range of aquatic habitats today. The land plants evolved from the algae, more specifically green algae. Some 400 million years ago freshwater, green, filamentous algae invaded the land. These probably had an isomorphic alternation of generations and were probably heterotrichous. Fossils of isolated land plant spores suggest land plants may have been around as long as 475 million years ago.
# Fresh-water algae
# Algae and symbioses
Some species of algae form symbiotic relationships with other organisms. In these symbioses, the algae supply photosynthates (organic substances) to the host organism providing protection to the algal cells. The host organism derives some or all of its energy requirements from the algae. Examples include
- lichens: a fungus is the host, usually with a green alga or a cyanobacterium as its symbiont. Both fungal and algal species found in lichens are capable of living independently, although habitat requirements may be greatly different from those of the lichen pair.
- corals: algae known as zooxanthellae are symbionts with corals. Notable amongst these is the dinoflagellate Symbiodinium, found in many hard corals. The loss of Symbiodinium, or other zooxanthellae, from the host is known as coral bleaching.
- sponges: green algae live close to the surface of some sponges, for example, breadcrumb sponge (Halichondria panicea). The alga is thus protected from predators; the sponge is provided with oxygen and sugars which can account for 50 to 80% of sponge growth in some species.
# Life-cycle
Rhodophyta, Chlorophyta and Heterokontophyta, the three main algal Phyla, have life-cycles which show tremendous variation with considerable complexity. In general there is an asexual phase where the seaweed's cells are diploid, a sexual phase where the cells are haploid followed by fusion of the male and female gametes. Asexual reproduction is advantageous in that it permits efficient population increases, but less variation is possible. Sexual reproduction allows more variation but is more costly because of the waste of gametes that fail to mate, among other things. Often there is no strict alternation between the sporophyte and gametophyte phases and also because there is often an asexual phase, which could include the fragmentation of the thallus. | Algae
# Overview
Algae have conventionally been regarded as simple plants within the study of botany. All are Eukaryota, though Chromophyta have Bacterial (see Blue-green algae) characteristics and some authorities consider them all to be Protists, however this view is now considered to be outdated.[1] They may still be included in the algae as plants. Some authors often include the blue-green algae (Cyanophyta) but note that they are not eukaryote. Algae do not represent a single evolutionary direction or line but a level of organization that may have developed several times in the early history of life on Earth.
The protists are traditionally considered more animal-like (see Protozoa).
The prokaryotic forms, referred to as blue-green algae are only half-algae with a mixture of bacterial characteristics. However, they are quite distant from the bacteria and are referred to by some as Cyanochloronta. All other forms belong as true eukaryota algae within the study of Botany, they have a nucleus enclosed within a membrane.[2] The protoctists are defined by some as eukaryotic microorganisms with the exception of animals and plants and including fungi and algae, slime moulds and other obscure eukaryotes.[3] There is still some disagreement on some of these matters.
Algae range from single-cell organisms to multicellular organisms, some with fairly complex differentiated form and (if marine) called seaweeds. All lack leaves, roots, flowers, seeds and other organ structures that characterize higher plants (vascular plants). They are distinguished from other protozoa in that they are photoautotrophic although this is not a hard or vast distinction as some groups contain members that are mixotrophic, deriving energy both from photosynthesis and uptake of organic carbon either by osmotrophy, myzotrophy, or phagotrophy. Some unicellular species rely entirely on external energy sources and have reduced or lost their photosynthetic apparatus.
All algae have photosynthetic machinery ultimately derived from the cyanobacteria, and so produce oxygen as a byproduct of photosynthesis, unlike non-cyanobacterial photosynthetic bacteria. It is estimated that algae produce about 73 to 87 percent of the net global production of oxygen[4] - which is available to humans and other animals for respiration.
# Ecology
Algae are usually found in damp places or bodies of water and thus are common in terrestrial as well as aquatic environments. However, terrestrial algae are usually rather inconspicuous and far more common in moist, tropical regions than dry ones, because algae lack vascular tissues and other adaptations to live on land. Algae can, however, endure dryness and other conditions in symbiosis with a fungus as lichen.
The various sorts of algae play significant roles in aquatic ecology. Microscopic forms that live suspended in the water column — called phytoplankton — provide the food base for most marine food chains. In very high densities (so-called algal blooms) these algae may discolor the water and outcompete or poison other life forms. Seaweeds grow mostly in shallow marine waters, however some have been recorded to a depth of 300 m.[2]Some are used as human food or harvested for useful substances such as agar or fertilizer.
# Study of algae
The study of marine and freshwater algae is called phycology or algology.
The US Algal Collection is represented by almost 300,000 accessioned and inventoried herbarium specimens.[1]
# Classification
## Prokaryotic algae
Cyanobacteria have been included among the algae, referred to as the cyanophytes or Blue-green algae, (the term "algae" refers to any aquatic organisms capable of photosynthesis)[5] though some recent treatises on algae specifically exclude them. Cyanobacteria are some of the oldest organisms to appear in the fossil record dating back to the Precambrian, possibly as far as about 3.5 billion years.[6] Ancient cyanobacteria likely produced much of the oxygen in the Earth's atmosphere.
Cyanobacteria can be unicellular, colonial, or filamentous. They have a prokaryotic cell structure typical of bacteria and conduct photosynthesis on specialized cytoplasmic membranes called thylakoid membranes, rather than in organelles. Some filamentous blue-green algae have specialized cells, termed heterocysts, in which nitrogen fixation occurs.[7] the perfect prokaryotic cell consist of miscalgnous sheath covering cellwall that consistof pectinic substance and sachride while the cellwall consist of 4 layer outer and inner and middle layer while the fourth layer is attached to plasma membrane and the protoplast consist of 2 part peripheral coloured partknown by chromatoplasm which contain the pigments in case of algae and contain photothynsis producte.g in cyanobacteria it contain chlorophylla, b-caroteinand c-phycocyanin and c-phycoerthyrin
## Eukaryotic algae
All other algae are eukaryotes and conduct photosynthesis within membrane-bound structures (organelles) called chloroplasts. Chloroplasts contain DNA and are similar in structure to cyanobacteria, presumably representing reduced cyanobacterial endosymbionts. The exact nature of the chloroplasts is different among the different lines of algae, reflecting different endosymbiotic events. The table below lists the three major groups of eukaryotic algae and their lineage relationship is shown in the figure on the left. Note many of these groups contain some members that are no longer photosynthetic. Some retain plastids, but not chloroplasts, while others have lost them entirely.
It was W.H.Harvey (1811 — 1866) who first divided the algae into four divisions based on their pigmentation. This is the first use of a biochemical criterion in plant systematics. Harvey's four divisions were: red algae (Rhodophyta), brown algae (Heteromontophyta), green algae (Chlorophyta) and Diatomaceae (Dixon, 1973 p.232).
# Forms of algae
Most of the simpler algae are unicellular flagellates or amoeboids, but colonial and non-motile forms have developed independently among several of the groups. Some of the more common organizational levels, more than one of which may occur in the life cycle of a species, are
- Colonial: small, regular groups of motile cells
- Capsoid: individual non-motile cells embedded in mucilage
- Coccoid: individual non-motile cells with cell walls
- Palmelloid: non-motile cells embedded in mucilage
- Filamentous: a string of non-motile cells connected together, sometimes branching
- Parenchymatous: cells forming a thallus with partial differentiation of tissues
In three lines even higher levels of organization have been reached, imma hit with full tissue differentiation. These are the brown algae [2]—some of which may reach 50 m in length (kelps)[8]—the red algae [3], and the green algae [4]. The most complex forms are found among the green algae (see Charales and Charophyta), in a lineage that eventually led to the higher land plants. The point where these non-algal plants begin and algae stop is usually taken to be the presence of reproductive organs with protective cell layers, a characteristic not found in the other alga groups.
The first plants on earth were algae and these still thrive in a range of aquatic habitats today. The land plants evolved from the algae, more specifically green algae. Some 400 million years ago freshwater, green, filamentous algae invaded the land. These probably had an isomorphic alternation of generations and were probably heterotrichous. Fossils of isolated land plant spores suggest land plants may have been around as long as 475 million years ago.
# Fresh-water algae
# Algae and symbioses
Some species of algae form symbiotic relationships with other organisms. In these symbioses, the algae supply photosynthates (organic substances) to the host organism providing protection to the algal cells. The host organism derives some or all of its energy requirements from the algae. Examples include
- lichens: a fungus is the host, usually with a green alga or a cyanobacterium as its symbiont. Both fungal and algal species found in lichens are capable of living independently, although habitat requirements may be greatly different from those of the lichen pair.
- corals: algae known as zooxanthellae are symbionts with corals. Notable amongst these is the dinoflagellate Symbiodinium, found in many hard corals. The loss of Symbiodinium, or other zooxanthellae, from the host is known as coral bleaching.
- sponges: green algae live close to the surface of some sponges, for example, breadcrumb sponge (Halichondria panicea). The alga is thus protected from predators; the sponge is provided with oxygen and sugars which can account for 50 to 80% of sponge growth in some species.[9]
# Life-cycle
Rhodophyta, Chlorophyta and Heterokontophyta, the three main algal Phyla, have life-cycles which show tremendous variation with considerable complexity. In general there is an asexual phase where the seaweed's cells are diploid, a sexual phase where the cells are haploid followed by fusion of the male and female gametes. Asexual reproduction is advantageous in that it permits efficient population increases, but less variation is possible. Sexual reproduction allows more variation but is more costly because of the waste of gametes that fail to mate, among other things. Often there is no strict alternation between the sporophyte and gametophyte phases and also because there is often an asexual phase, which could include the fragmentation of the thallus.[8][10][5] | https://www.wikidoc.org/index.php/Algae | |
3cd25b3ca6ed5ad9821522554d9b6999ff70b142 | wikidoc | Amine | Amine
Amines are organic compounds and a type of functional group that contain nitrogen as the key atom. In structure, amines resemble ammonia, wherein one or more hydrogen atoms are replaced by organic substituents such as alkyl and aryl groups. An important exception to this rule is that compounds of the type RC(O)NR2, where the C(O) refers to a carbonyl group, are called amides rather than amines. Amides and amines have different structures and properties, so the distinction is chemically important. Somewhat confusing is the fact that amines in which an N-H group has been replaced by an N-M group (M = metal) are also called amides. Thus (CH3)2NLi is lithium dimethylamide.
Amines are central in organic chemistry. All known life processes depend on amino acids, each of which contains an amine group.
See Category:Amines for a list of types of amine and some real examples of this class of chemical.
# Introduction
## Aliphatic Amines
As displayed in the images below, primary amines arise when one of three hydrogen atoms in ammonia is replaced by an organic substituent. Secondary amines have two organic substituents bound to N together with one H. In tertiary amines all three hydrogen atoms are replaced by organic substituents. It is also possible to have four alkyl substituents on the nitrogen. These compounds have a charged nitrogen center, and necessarily come with a negative counterion, so they are called quaternary ammonium salts.
Similarly, an organic compound with multiple amino groups is called a diamine, triamine, tetraamine and so forth.
## Aromatic amines
Aromatic amines have the nitrogen atom connected to an aromatic ring as in anilines. The aromatic ring strongly decreases the basicity of the amine, depending on its substituents. Interestingly, the presence of an amine group strongly increases the reactivity of the aromatic ring, due to an electron-donating effect. One organic reaction involving aromatic amines is the Goldberg reaction.
# Naming conventions
- the prefix "N-" shows substitution on the nitrogen atom
- as prefix: "amino-"
- as suffix: "-amine"
- remember that chemical compounds are not proper nouns, so lower case is indicated throughout.
Systematic names for some common amines:
- Primary amines:
methylamine
ethanolamine or 2-aminoethanol
trisamine (or more commonly tris) (Its HCl salt is used as a pH buffering agent in biochemistry)
- methylamine
- ethanolamine or 2-aminoethanol
- trisamine (or more commonly tris) (Its HCl salt is used as a pH buffering agent in biochemistry)
- Secondary amines:
dimethylamine
methylethanolamine or 2-(methylamino)ethanol
Cyclic amines:
aziridine (3-member ring),
azetidine (4-member ring),
pyrrolidine (5-member ring) and
piperidine (6-member ring)
- dimethylamine
- methylethanolamine or 2-(methylamino)ethanol
- Cyclic amines:
aziridine (3-member ring),
azetidine (4-member ring),
pyrrolidine (5-member ring) and
piperidine (6-member ring)
- aziridine (3-member ring),
- azetidine (4-member ring),
- pyrrolidine (5-member ring) and
- piperidine (6-member ring)
- Tertiary amines:
trimethylamine
methyldiethanolamine (MDEA)
dimethylethanolamine (DMEA) or 2-(dimethylamino)ethanol
bis-tris (It is used as a pH buffering agent in biochemistry)
- trimethylamine
- methyldiethanolamine (MDEA)
- dimethylethanolamine (DMEA) or 2-(dimethylamino)ethanol
- bis-tris (It is used as a pH buffering agent in biochemistry)
# Physical properties
## General properties
- Hydrogen bonding significantly influences the properties of primary and secondary amines as well as the protonated derivatives of all amines. Thus the boiling point of amines is higher than those of the corresponding phosphines, but generally lower than those of the corresponding alcohols. Alcohols, or alkanols, resemble amines but feature an -OH group in place of NR2. Since oxygen is more electronegative than nitrogen, RO-H is typically more acidic than the related R2N-H compound.
- Methyl-, dimethyl-, trimethyl-, and ethylamine are gases under standard conditions, whereas diethylamine and triethylamine are liquids. Most other common alkyl amines are liquids; high-molecular-weight amines are, of course, solids.
- Gaseous amines possess a characteristic ammonia smell, liquid amines have a distinctive "fishy" smell.
- Most aliphatic amines display some solubility in water, reflecting their ability to form hydrogen bonds. Solubility decreases with the increase in the number of carbon atoms, especially when the carbon atom number is greater than 6.
- Aliphatic amines display significant solubility in organic solvents, especially polar organic solvents. Primary amines react with ketones such as acetone, and most amines are incompatible with chloroform and carbon tetrachloride.
- The aromatic amines, such as aniline, have their lone pair electrons conjugated into the benzene ring, thus their tendency to engage in hydrogen bonding is diminished. Otherwise they display the following properties:
Their boiling points are usually still high due to their larger size.
Diminished solubility in water, although they retain their solubility in suitable organic solvents only.
They are toxic and are easily absorbed through the skin: thus hazardous.
- Their boiling points are usually still high due to their larger size.
- Diminished solubility in water, although they retain their solubility in suitable organic solvents only.
- They are toxic and are easily absorbed through the skin: thus hazardous.
## Chirality
Tertiary amines of the type NHRR' and NRR'R" are chiral: the nitrogen atom bears four distinct substituents counting the lone pair. The energy barrier for the inversion of the stereocenter is relatively low, e.g., ~7 kcal/mol for a trialkylamine. The interconversion of the stereoisomers has been compared to the inversion of an open umbrella in to a strong wind. Because of this low barrier, amines such as NHRR' cannot be resolved optically and NRR'R" can only be resolved when the R, R', and R" groups are constrained in cyclic structures.
## Properties as bases
Like ammonia, amines act as bases and are reasonably strong (see table for examples of conjugate acid Ka values). The basicity of amines depends on:
- The availability of the lone pair of electrons on the Nitrogen atom.
- The electronic properties of the substituents (alkyl groups enhance the basicity, aryl groups diminish it).
- The degree of solvation of the protonated amine.
The nitrogen atom features a lone electron pair that can bind H+ to form an ammonium ion R3NH+. The lone electron pair is represented in this article by a two dots above or next to the N. The water solubility of simple amines is largely due to hydrogen bonding between protons on the water molecules and these lone electron pairs.
- Inductive effect of alkyl groups
- Mesomeric effect of aromatic systems
The degree of protonation of protonated amines:
# Synthesis
The following laboratory methods exist for the preparation of amines:
- via the Gabriel synthesis:
- via azides by the Staudinger reduction.
- From carboxylic acids in the Schmidt reaction.
- Allylic amines can be prepared from imines in the Aza-Baylis-Hillman reaction.
- via Hofmann degradation of amides. This reaction is valid for preparation of primary amines only. Gives good yields of primary amines uncontaminated with other amines.
- Quaternary ammonium salts upon treatment with strong base undergo the so-called Hofmann Elimination
- Reduction of nitriles, amides and nitro compounds:
- Nucleophilic substitution of haloalkanes . Primary amines can also be synthesized by alkylaton of ammonia. Haloalkanes react with amines to give a corresponding alkyl-substituted amine, with the release of a halogen acid. Such reactions, which are most useful for alkyl iodides and bromides, are rarely employed because the degree of alkylation is difficult to control. If the reacting amine is tertiary, a quaternary ammonium cation results in the Menshutkin reaction. Many quaternary ammonium salts can be prepared by this route with diverse R groups and many halide and pseudohalide anions.
- via halides and hexamine in the Delepine reaction
- aryl amines can be obtained from amines and aryl halides in the Buchwald-Hartwig reaction
- from alkenes and alkynes in hydroamination
# Reactions
Amines react in a variety of ways:
- By nucleophilic acyl substitution. Acyl chlorides and acid anhydrides react with primary and secondary amines in cold to form amides in the Schotten-Baumann reaction. Tertiary amines cannot be acylated due to the absence of a replaceable hydrogen atom. With the much less active benzoyl chloride, acylation can still be performed by the use of excess aqeous alkali to facilitate the reaction.
- By ammonium salt formation. Amines R3N react with strong acids such as hydroiodic acid, hydrobromic acid and hydrochloric acid in neutralization reactions forming ammonium salts R3NH+.
- By diazonium salt formation. Nitrous acid with formula HNO2 is unstable, therefore usually a mixture of NaNO2 and dilute hydrochloric acid or sulfuric acid is used to produce nitrous acid indirectly. Primary aliphatic amines with nitrous acid give very unstable diazonium salts which spontaneously decompose by losing N2 to form carbonium ion. The carbonium ion goes on to produce a mixture of alkenes, alkanols or alkyl halides, with alkanols as the major product. This reaction is of little synthetic importance because the diazonium salt formed is too unstable, even at cold conditions.
- By imine formation. Primary amines react with ketones and aldehydes to form imines. In the case of formaldehyde (R' = H), these products are typically cyclic trimers.
- By oxidation to nitroso compounds, for instance with peroxymonosulfuric acid.
- By reduction of quaternary ammonium cations to tertiary amines in the Emde degradation.
- By rearrangement of N-alkyl anilines to aryl substituted anilines in the Hofmann-Martius rearrangement.
- primary and secondary amines react with pyridinium salts in the Zincke reaction
# Biological activity
Amines have strong, characteristic, disagreeable odors, and are toxic. The smells of ammonia, old fish, urine, rotting flesh, and semen are all mainly composed of amines. Many kinds of biological activity produce amines by breakdown of amino acids.
# Use of amines
## Dyes
Primary aromatic amines are used as a starting material for the manufacture of azo dyes. It reacts with nitric(III) acid to form diazonium salt, which can undergo coupling reaction to form azo compound. As azo-compounds are highly coloured, they are widely used in dyeing industries, such as:
- Methyl orange
- Direct brown 138
- Sunset yellow FCF
- Ponceau
## Drugs
- Chlorpheniramine is an antihistamine that helps to relieve allergic disorders due to cold, hay fever, itchy skin, insect bites and stings.
- Chlorpromazine is a tranquillizer that sedates without inducing sleep. It is used to relieve anxiety, excitement, restlessness or even mental disorder.
- Ephedrine and Phenylephrine, as amine hydrochlorides, are used as decongestants.
- Amphetamine, Methamphetamine, and Methcathinone are amines that are listed as controlled substances by the DEA.
- Amitriptyline, Imipramine, Lofepramine and Clomipramine are tricylic antidepressants and tertiary amines
- Nortriptyline, Desipramine, and Amoxapine are tricyclic antidepressants and secondary amines
- (The tricylics are grouped by the nature of the final amine group on the side chain.)
## Gas Treatment
- Aqueous monoethanolamine (MEA), diglycolamine (DGA), diethanolamine (DEA), diisopropanolamine (DIPA) and methyldiethanolamine (MDEA) are widely used industrially for removing carbon dioxide (CO2) and hydrogen sulphide (H2S) from natural gas streams and refinery process streams. They may also be used to remove CO2 from combustion gases / flue gases and may have potential for abatement of greenhouse gases. | Amine
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Amines are organic compounds and a type of functional group that contain nitrogen as the key atom. In structure, amines resemble ammonia, wherein one or more hydrogen atoms are replaced by organic substituents such as alkyl and aryl groups. An important exception to this rule is that compounds of the type RC(O)NR2, where the C(O) refers to a carbonyl group, are called amides rather than amines. Amides and amines have different structures and properties, so the distinction is chemically important. Somewhat confusing is the fact that amines in which an N-H group has been replaced by an N-M group (M = metal) are also called amides. Thus (CH3)2NLi is lithium dimethylamide.
Amines are central in organic chemistry. All known life processes depend on amino acids, each of which contains an amine group.
See Category:Amines for a list of types of amine and some real examples of this class of chemical.
# Introduction
## Aliphatic Amines
As displayed in the images below, primary amines arise when one of three hydrogen atoms in ammonia is replaced by an organic substituent. Secondary amines have two organic substituents bound to N together with one H. In tertiary amines all three hydrogen atoms are replaced by organic substituents. It is also possible to have four alkyl substituents on the nitrogen. These compounds have a charged nitrogen center, and necessarily come with a negative counterion, so they are called quaternary ammonium salts.
Similarly, an organic compound with multiple amino groups is called a diamine, triamine, tetraamine and so forth.
## Aromatic amines
Aromatic amines have the nitrogen atom connected to an aromatic ring as in anilines. The aromatic ring strongly decreases the basicity of the amine, depending on its substituents. Interestingly, the presence of an amine group strongly increases the reactivity of the aromatic ring, due to an electron-donating effect. One organic reaction involving aromatic amines is the Goldberg reaction.
# Naming conventions
- the prefix "N-" shows substitution on the nitrogen atom
- as prefix: "amino-"
- as suffix: "-amine"
- remember that chemical compounds are not proper nouns, so lower case is indicated throughout.
Systematic names for some common amines:
- Primary amines:
methylamine
ethanolamine or 2-aminoethanol
trisamine (or more commonly tris) (Its HCl salt is used as a pH buffering agent in biochemistry)
- methylamine
- ethanolamine or 2-aminoethanol
- trisamine (or more commonly tris) (Its HCl salt is used as a pH buffering agent in biochemistry)
- Secondary amines:
dimethylamine
methylethanolamine or 2-(methylamino)ethanol
Cyclic amines:
aziridine (3-member ring),
azetidine (4-member ring),
pyrrolidine (5-member ring) and
piperidine (6-member ring)
- dimethylamine
- methylethanolamine or 2-(methylamino)ethanol
- Cyclic amines:
aziridine (3-member ring),
azetidine (4-member ring),
pyrrolidine (5-member ring) and
piperidine (6-member ring)
- aziridine (3-member ring),
- azetidine (4-member ring),
- pyrrolidine (5-member ring) and
- piperidine (6-member ring)
- Tertiary amines:
trimethylamine
methyldiethanolamine (MDEA)
dimethylethanolamine (DMEA) or 2-(dimethylamino)ethanol
bis-tris (It is used as a pH buffering agent in biochemistry)
- trimethylamine
- methyldiethanolamine (MDEA)
- dimethylethanolamine (DMEA) or 2-(dimethylamino)ethanol
- bis-tris (It is used as a pH buffering agent in biochemistry)
# Physical properties
## General properties
- Hydrogen bonding significantly influences the properties of primary and secondary amines as well as the protonated derivatives of all amines. Thus the boiling point of amines is higher than those of the corresponding phosphines, but generally lower than those of the corresponding alcohols. Alcohols, or alkanols, resemble amines but feature an -OH group in place of NR2. Since oxygen is more electronegative than nitrogen, RO-H is typically more acidic than the related R2N-H compound.
- Methyl-, dimethyl-, trimethyl-, and ethylamine are gases under standard conditions, whereas diethylamine and triethylamine are liquids. Most other common alkyl amines are liquids; high-molecular-weight amines are, of course, solids.
- Gaseous amines possess a characteristic ammonia smell, liquid amines have a distinctive "fishy" smell.
- Most aliphatic amines display some solubility in water, reflecting their ability to form hydrogen bonds. Solubility decreases with the increase in the number of carbon atoms, especially when the carbon atom number is greater than 6.
- Aliphatic amines display significant solubility in organic solvents, especially polar organic solvents. Primary amines react with ketones such as acetone, and most amines are incompatible with chloroform and carbon tetrachloride.
- The aromatic amines, such as aniline, have their lone pair electrons conjugated into the benzene ring, thus their tendency to engage in hydrogen bonding is diminished. Otherwise they display the following properties:
Their boiling points are usually still high due to their larger size.
Diminished solubility in water, although they retain their solubility in suitable organic solvents only.
They are toxic and are easily absorbed through the skin: thus hazardous.
- Their boiling points are usually still high due to their larger size.
- Diminished solubility in water, although they retain their solubility in suitable organic solvents only.
- They are toxic and are easily absorbed through the skin: thus hazardous.
## Chirality
Tertiary amines of the type NHRR' and NRR'R" are chiral: the nitrogen atom bears four distinct substituents counting the lone pair. The energy barrier for the inversion of the stereocenter is relatively low, e.g., ~7 kcal/mol for a trialkylamine. The interconversion of the stereoisomers has been compared to the inversion of an open umbrella in to a strong wind. Because of this low barrier, amines such as NHRR' cannot be resolved optically and NRR'R" can only be resolved when the R, R', and R" groups are constrained in cyclic structures.
## Properties as bases
Like ammonia, amines act as bases and are reasonably strong (see table for examples of conjugate acid Ka values). The basicity of amines depends on:
- The availability of the lone pair of electrons on the Nitrogen atom.
- The electronic properties of the substituents (alkyl groups enhance the basicity, aryl groups diminish it).
- The degree of solvation of the protonated amine.
The nitrogen atom features a lone electron pair that can bind H+ to form an ammonium ion R3NH+. The lone electron pair is represented in this article by a two dots above or next to the N. The water solubility of simple amines is largely due to hydrogen bonding between protons on the water molecules and these lone electron pairs.
- Inductive effect of alkyl groups
- Mesomeric effect of aromatic systems
The degree of protonation of protonated amines:
# Synthesis
The following laboratory methods exist for the preparation of amines:
- via the Gabriel synthesis:
- via azides by the Staudinger reduction.
- From carboxylic acids in the Schmidt reaction.
- Allylic amines can be prepared from imines in the Aza-Baylis-Hillman reaction.
- via Hofmann degradation of amides. This reaction is valid for preparation of primary amines only. Gives good yields of primary amines uncontaminated with other amines.
- Quaternary ammonium salts upon treatment with strong base undergo the so-called Hofmann Elimination
- Reduction of nitriles, amides and nitro compounds:
- Nucleophilic substitution of haloalkanes [1]. Primary amines can also be synthesized by alkylaton of ammonia. Haloalkanes react with amines to give a corresponding alkyl-substituted amine, with the release of a halogen acid. Such reactions, which are most useful for alkyl iodides and bromides, are rarely employed because the degree of alkylation is difficult to control. If the reacting amine is tertiary, a quaternary ammonium cation results in the Menshutkin reaction. Many quaternary ammonium salts can be prepared by this route with diverse R groups and many halide and pseudohalide anions.
- via halides and hexamine in the Delepine reaction
- aryl amines can be obtained from amines and aryl halides in the Buchwald-Hartwig reaction
- from alkenes and alkynes in hydroamination
# Reactions
Amines react in a variety of ways:
- By nucleophilic acyl substitution. Acyl chlorides and acid anhydrides react with primary and secondary amines in cold to form amides in the Schotten-Baumann reaction. Tertiary amines cannot be acylated due to the absence of a replaceable hydrogen atom. With the much less active benzoyl chloride, acylation can still be performed by the use of excess aqeous alkali to facilitate the reaction.
- By ammonium salt formation. Amines R3N react with strong acids such as hydroiodic acid, hydrobromic acid and hydrochloric acid in neutralization reactions forming ammonium salts R3NH+.
- By diazonium salt formation. Nitrous acid with formula HNO2 is unstable, therefore usually a mixture of NaNO2 and dilute hydrochloric acid or sulfuric acid is used to produce nitrous acid indirectly. Primary aliphatic amines with nitrous acid give very unstable diazonium salts which spontaneously decompose by losing N2 to form carbonium ion. The carbonium ion goes on to produce a mixture of alkenes, alkanols or alkyl halides, with alkanols as the major product. This reaction is of little synthetic importance because the diazonium salt formed is too unstable, even at cold conditions.
- By imine formation. Primary amines react with ketones and aldehydes to form imines. In the case of formaldehyde (R' = H), these products are typically cyclic trimers.
- By oxidation to nitroso compounds, for instance with peroxymonosulfuric acid.
- By reduction of quaternary ammonium cations to tertiary amines in the Emde degradation.
- By rearrangement of N-alkyl anilines to aryl substituted anilines in the Hofmann-Martius rearrangement.
- primary and secondary amines react with pyridinium salts in the Zincke reaction
# Biological activity
Amines have strong, characteristic, disagreeable odors, and are toxic. The smells of ammonia, old fish, urine, rotting flesh, and semen are all mainly composed of amines. Many kinds of biological activity produce amines by breakdown of amino acids.
# Use of amines
## Dyes
Primary aromatic amines are used as a starting material for the manufacture of azo dyes. It reacts with nitric(III) acid to form diazonium salt, which can undergo coupling reaction to form azo compound. As azo-compounds are highly coloured, they are widely used in dyeing industries, such as:
- Methyl orange
- Direct brown 138
- Sunset yellow FCF
- Ponceau
## Drugs
- Chlorpheniramine is an antihistamine that helps to relieve allergic disorders due to cold, hay fever, itchy skin, insect bites and stings.
- Chlorpromazine is a tranquillizer that sedates without inducing sleep. It is used to relieve anxiety, excitement, restlessness or even mental disorder.
- Ephedrine and Phenylephrine, as amine hydrochlorides, are used as decongestants.
- Amphetamine, Methamphetamine, and Methcathinone are amines that are listed as controlled substances by the DEA.
- Amitriptyline, Imipramine, Lofepramine and Clomipramine are tricylic antidepressants and tertiary amines
- Nortriptyline, Desipramine, and Amoxapine are tricyclic antidepressants and secondary amines
- (The tricylics are grouped by the nature of the final amine group on the side chain.)
## Gas Treatment
- Aqueous monoethanolamine (MEA), diglycolamine (DGA), diethanolamine (DEA), diisopropanolamine (DIPA) and methyldiethanolamine (MDEA) are widely used industrially for removing carbon dioxide (CO2) and hydrogen sulphide (H2S) from natural gas streams and refinery process streams. They may also be used to remove CO2 from combustion gases / flue gases and may have potential for abatement of greenhouse gases. | https://www.wikidoc.org/index.php/Aliphatic_Amines | |
aef111a20ab06ec0bb44acb234f953a796739bbe | wikidoc | Alloy | Alloy
# Overview
An alloy is a solid solution or homogeneous mixture of two or more elements, at least one of which is a metal, which itself has metallic properties. It usually has different properties from those of its component elements.
Alloying one metal with others often enhances its properties.
For instance, steel is stronger than iron, its primary element. The physical properties, such as density, reactivity, Young's modulus, and electrical and thermal conductivity, of an alloy may not differ greatly from those of its elements, but engineering properties, such as tensile strength and shear strength may be substantially different from those of the constituent materials. This is sometimes due to the sizes of the atoms in the alloy, since larger atoms exert a compressive force on neighboring atoms, and smaller atoms exert a tensile force on their neighbors, helping the alloy resist deformation. Alloys may exhibit marked differences in behavior even when small amounts of one element occur. For example, impurities in semi-conducting ferromagnetic alloys lead to different properties, as first predicted by White, Hogan, Suhl, Tian Abrie and Nakamura.
Some alloys are made by melting and mixing two or more metals. Brass is an alloy made from copper and zinc. Bronze, used for statues, ornaments and church bells, is an alloy of tin and copper.
Unlike pure metals, most alloys do not have a single melting point. Instead, they have a melting range in which the material is a mixture of solid and liquid phases. The temperature at which melting begins is called the solidus and the temperature when melting is complete is called the liquidus. However, for most alloys there is a particular proportion of constituents which give them a single melting point or (rarely) two. This is called the alloy's eutectic mixture.
# Classification
Alloys can be classified by the number of their constituents. An alloy with two components is called a binary alloy; one with three is a ternary alloy, and so forth. Alloys can be further classified as either substitution alloys or interstitial alloys, depending on their method of formation. In substitution alloys, the atoms of the components are approximately the same size and the various atoms are simply substituted for one another in the crystal structure. An example of a (binary) substitution alloy is brass, made up of copper and zinc. Interstitial alloys occur when the atoms of one component are substantially smaller than the other and the smaller atoms fit into the spaces (interstices) between the larger atoms.
# Terminology
In practice, some alloys are used so predominantly with respect to their base metals that the name of the primary constituent is also used as the name of the alloy. For example, 14 karat gold is an alloy of gold with other elements. Similarly, the silver used in jewelry and the aluminium used as a structural building material are also alloys.
The term "alloy" is sometime used in everyday speech as a synonym for a particular alloy. For example, automobile wheels made of aluminium alloy are commonly referred to as simply "alloy wheels". The usage is obviously indefinite, since steels and most other metals in practical use are also alloys. | Alloy
# Overview
An alloy is a solid solution or homogeneous mixture of two or more elements, at least one of which is a metal, which itself has metallic properties. It usually has different properties from those of its component elements.
Alloying one metal with others often enhances its properties.
For instance, steel is stronger than iron, its primary element. The physical properties, such as density, reactivity, Young's modulus, and electrical and thermal conductivity, of an alloy may not differ greatly from those of its elements, but engineering properties, such as tensile strength[1] and shear strength may be substantially different from those of the constituent materials. This is sometimes due to the sizes of the atoms in the alloy, since larger atoms exert a compressive force on neighboring atoms, and smaller atoms exert a tensile force on their neighbors, helping the alloy resist deformation. Alloys may exhibit marked differences in behavior even when small amounts of one element occur. For example, impurities in semi-conducting ferromagnetic alloys lead to different properties, as first predicted by White, Hogan, Suhl, Tian Abrie and Nakamura.[2][3]
Some alloys are made by melting and mixing two or more metals. Brass is an alloy made from copper and zinc. Bronze, used for statues, ornaments and church bells, is an alloy of tin and copper.
Unlike pure metals, most alloys do not have a single melting point. Instead, they have a melting range in which the material is a mixture of solid and liquid phases. The temperature at which melting begins is called the solidus and the temperature when melting is complete is called the liquidus. However, for most alloys there is a particular proportion of constituents which give them a single melting point or (rarely) two. This is called the alloy's eutectic mixture.
# Classification
Alloys can be classified by the number of their constituents. An alloy with two components is called a binary alloy; one with three is a ternary alloy, and so forth. Alloys can be further classified as either substitution alloys or interstitial alloys, depending on their method of formation. In substitution alloys, the atoms of the components are approximately the same size and the various atoms are simply substituted for one another in the crystal structure. An example of a (binary) substitution alloy is brass, made up of copper and zinc. Interstitial alloys occur when the atoms of one component are substantially smaller than the other and the smaller atoms fit into the spaces (interstices) between the larger atoms.
# Terminology
In practice, some alloys are used so predominantly with respect to their base metals that the name of the primary constituent is also used as the name of the alloy. For example, 14 karat gold is an alloy of gold with other elements. Similarly, the silver used in jewelry and the aluminium used as a structural building material are also alloys.
The term "alloy" is sometime used in everyday speech as a synonym for a particular alloy. For example, automobile wheels made of aluminium alloy are commonly referred to as simply "alloy wheels". The usage is obviously indefinite, since steels and most other metals in practical use are also alloys. | https://www.wikidoc.org/index.php/Alloy | |
d654750cdcc20624d22678d4daa9b8a0703c6026 | wikidoc | Allyl | Allyl
# Overview
An allyl group is an alkene hydrocarbon group with the formula H2C=CH-CH2-. It is made up of a vinyl group, CH2=CH-, attached to a methylene -CH2. For example allyl alcohol has the structure H2C=CH-CH2OH . Compounds containing the allyl group are often referred to as being allylic.
Allylic carbons are sp3 hybridized, vinylic carbons are sp2 hybridized.
The site of the saturated carbon atom, where the vinyl group attaches (e.g. next to the OH in allyl alcohol) is called the allylic position or allylic site. A group, such as -OH, attached at an allylic site is sometimes described as allylic. Two examples of simple allyl compounds are allyl chloride and allyl alcohol.
Substituted versions of the above, such as the trans-but-2-en-1-yl or crotyl group (CH3CH=CH-CH2-) may be also referred to as allylic groups.
Allylic methylene groups show special reactivity such as demonstrated in allylic oxidations, ene reactions and the Trost asymmetric allylic alkylation. | Allyl
# Overview
An allyl group is an alkene hydrocarbon group with the formula H2C=CH-CH2-. It is made up of a vinyl group, CH2=CH-, attached to a methylene -CH2. For example allyl alcohol has the structure H2C=CH-CH2OH . Compounds containing the allyl group are often referred to as being allylic.
Allylic carbons are sp3 hybridized, vinylic carbons are sp2 hybridized.
The site of the saturated carbon atom, where the vinyl group attaches (e.g. next to the OH in allyl alcohol) is called the allylic position or allylic site. A group, such as -OH, attached at an allylic site is sometimes described as allylic. Two examples of simple allyl compounds are allyl chloride and allyl alcohol.
Substituted versions of the above, such as the trans-but-2-en-1-yl or crotyl group (CH3CH=CH-CH2-) may be also referred to as allylic groups.
Allylic methylene groups show special reactivity such as demonstrated in allylic oxidations, ene reactions and the Trost asymmetric allylic alkylation. | https://www.wikidoc.org/index.php/Allyl | |
33b594f4e5d7b5c73cfc77c02adf269d0b1fd212 | wikidoc | PSEN1 | PSEN1
Presenilin-1 (PS-1) is a presenilin protein that in humans is encoded by the PSEN1 gene. Presenilin-1 is one of the four core proteins in the gamma secretase complex, which is considered to play an important role in generation of amyloid beta (Aβ) from amyloid precursor protein (APP). Accumulation of amyloid beta is associated with the onset of Alzheimer's disease.
# Structure
Presenilin possesses a 9 transmembrane domain topology, with an extracellular C-terminus and a cytosolic N-terminus. Presenilin undergoes endo-proteolytic processing to produce ~27-28 kDa N-terminal and ~16-17 kDa C-terminal fragments in humans. Furthermore, presenilin exists in the cell mainly as a heterodimer of the C-terminal and N-terminus fragments. When presenilin 1 is overexpressed, the full length protein accumulates in an inactive form. Based on evidence that a gamma-secretase inhibitor binds to the fragments, the cleaved presenilin complex is considered to be the active form.
# Function
Presenilins are postulated to regulate APP processing through their effects on gamma secretase, an enzyme that cleaves APP. Also, it is thought that the presenilins are involved in the cleavage of the Notch receptor, such that they either directly regulate gamma secretase activity or themselves are protease enzymes. Multiple alternatively spliced transcript variants have been identified for this gene, the full-length natures of only some have been determined.
## Notch signaling pathway
In Notch signaling, critical proteolytic reactions takes place during maturation and activation of Notch membrane receptor. Notch1 is cleaved extracellularlly at site1 (S1) and two polypeptides are produced to form a heterodimer receptor on the cell surface. After the formation of receptor, Notch1 is further cleaved in site 3(S3) and release Notch1 intracellular domain (NICD) from the membrane.
Presenilin 1 has been shown to play an important role in proteolytic process. In the prenilin 1 null mutant drosophila, Notch signaling is abolished and it displays a notch-like lethal phenotype. Moreover, in mammalian cells, deficiency of PSEN1 also causes the defect in the proteolytic release of NICD from a truncated Notch construct. The same step can be also blocked by several gamma-secretase inhibitors, shown in the same study. These evidences collectively suggest a critical role of presenilin 1 in the Notch signaling pathway.
## Wnt signaling pathway
Wnt signaling pathway has been shown to be involved in several critical steps in embryogenesis and development. Presenilin 1 has been shown to form a complex with beta-catenin, an important component in Wnt signaling, and stabilize beta-catenin. Mutant of presenilin-1 that reduces the ability to stabilize beta-catenin complex leads to hyperactive degradation of beta-catenin in the brains of transgenic mice.
Considered as a negative regulator in wnt signaling pathway, presenilin-1 was also found to play a role in beta-catenin phosphorylation. Beta-catenin is coupled by presenilin-1 and undergoes a sequential phosphorylation by two kinase activities. The study also further illustrates that the deficiency of presenilin 1 disconnects the sequential phosphorylation and thus disrupts the normal wnt signaling pathway.
# Clinical significance
## Beta-amyloid production
Transgenic mice that over-expressed mutant presenilin-1 show an increase of beta-amyloid-42(43) in the brain, which suggest presenilin-1 plays an important role in beta-amyloid regulation and can be highly related to Alzheimer's disease. Further study conducted in neuronal cultures derived from presenilin-1 deficient mouse embryos. They showed that cleavage by alpha- and beta- secretase was still normal without the presence of presenilin-1. Meanwhile, the cleavage by gamma-cleavage of the transmembrane domain of APP was abolished. A 5-fold drop of amyloid peptide was observed, suggesting that deficiency of presenilin-1 can down regulate amyloid and inhibition of presenilin-1 can be a potential method for anti-amyloidogenic therapy in Alzheimer's disease. Extensive study on the role of presenilin-1 in amyloid production has been conducted to improve our understanding of Alzheimer's disease.
## Alzheimer's disease
Alzheimer's disease (AD) patients with an inherited form of the disease may carry mutations in the presenilin proteins (PSEN1; PSEN2) or the amyloid precursor protein (APP). These disease-linked mutations result in increased production of the longer form of amyloid beta (main component of amyloid deposits found in AD brains). These mutations result in early-onset Alzheimer's Disease, which is a rare form of the disease. These rare genetic variants are autosomal dominant.
## Cancer
In addition to its role in Alzheimer's disease, presenilin-1 also found to be important in cancer. A study of broad range gene expression was conducted on human malignant melanoma. Researchers classified the malignant melanoma cell lines into two types. The study showed that presenilin-1 is down regulated in cell type while it is overexpressed in the other cell type. Another study on multidrug resistance (MDR) cell line also reveals a role of presenilin-1 in cancer development. Because of the development to the resistance to chemical, MDR cells become a critical factor on the success of cancer chemotherapy. In the study, researchers tried to explore the molecular mechanism by looking into the expression of Notch1 intracellular (N1IC) domain and presenilin 1. They found that there is higher level expression of both proteins and a multidrug resistance-associated protein 1 (ABCC1) was also found to be regulated by N1IC, which suggest a mechanism of ABCC1 regulated by presenilin 1 and notch signaling.
# Interactions
PSEN1 has been shown to interact with:
- BCL2,
- CTNNB1,
- CTNND1,
- FLNB,
- GFAP,
- Delta catenin,
- ICAM5,
- KCNIP3,
- NCSTN,
- PKP4, and
- UBQLN1. | PSEN1
Presenilin-1 (PS-1) is a presenilin protein that in humans is encoded by the PSEN1 gene.[1] Presenilin-1 is one of the four core proteins in the gamma secretase complex, which is considered to play an important role in generation of amyloid beta (Aβ) from amyloid precursor protein (APP). Accumulation of amyloid beta is associated with the onset of Alzheimer's disease.[2]
# Structure
Presenilin possesses a 9 transmembrane domain topology, with an extracellular C-terminus and a cytosolic N-terminus.[3][4] Presenilin undergoes endo-proteolytic processing to produce ~27-28 kDa N-terminal and ~16-17 kDa C-terminal fragments in humans.[5] Furthermore, presenilin exists in the cell mainly as a heterodimer of the C-terminal and N-terminus fragments.[5] When presenilin 1 is overexpressed, the full length protein accumulates in an inactive form.[6] Based on evidence that a gamma-secretase inhibitor binds to the fragments,[7] the cleaved presenilin complex is considered to be the active form.[8]
# Function
Presenilins are postulated to regulate APP processing through their effects on gamma secretase, an enzyme that cleaves APP. Also, it is thought that the presenilins are involved in the cleavage of the Notch receptor, such that they either directly regulate gamma secretase activity or themselves are protease enzymes. Multiple alternatively spliced transcript variants have been identified for this gene, the full-length natures of only some have been determined.[9]
## Notch signaling pathway
In Notch signaling, critical proteolytic reactions takes place during maturation and activation of Notch membrane receptor.[10] Notch1 is cleaved extracellularlly at site1 (S1) and two polypeptides are produced to form a heterodimer receptor on the cell surface.[11] After the formation of receptor, Notch1 is further cleaved in site 3(S3)[12] and release Notch1 intracellular domain (NICD) from the membrane.[13]
Presenilin 1 has been shown to play an important role in proteolytic process. In the prenilin 1 null mutant drosophila, Notch signaling is abolished and it displays a notch-like lethal phenotype.[14] Moreover, in mammalian cells, deficiency of PSEN1 also causes the defect in the proteolytic release of NICD from a truncated Notch construct. The same step can be also blocked by several gamma-secretase inhibitors, shown in the same study.[15] These evidences collectively suggest a critical role of presenilin 1 in the Notch signaling pathway.
## Wnt signaling pathway
Wnt signaling pathway has been shown to be involved in several critical steps in embryogenesis and development. Presenilin 1 has been shown to form a complex with beta-catenin, an important component in Wnt signaling, and stabilize beta-catenin.[16] Mutant of presenilin-1 that reduces the ability to stabilize beta-catenin complex leads to hyperactive degradation of beta-catenin in the brains of transgenic mice.[16]
Considered as a negative regulator in wnt signaling pathway, presenilin-1 was also found to play a role in beta-catenin phosphorylation.[17] Beta-catenin is coupled by presenilin-1 and undergoes a sequential phosphorylation by two kinase activities.[17] The study also further illustrates that the deficiency of presenilin 1 disconnects the sequential phosphorylation and thus disrupts the normal wnt signaling pathway.[17]
# Clinical significance
## Beta-amyloid production
Transgenic mice that over-expressed mutant presenilin-1 show an increase of beta-amyloid-42(43) in the brain, which suggest presenilin-1 plays an important role in beta-amyloid regulation and can be highly related to Alzheimer's disease.[18] Further study conducted in neuronal cultures derived from presenilin-1 deficient mouse embryos. They showed that cleavage by alpha- and beta- secretase was still normal without the presence of presenilin-1. Meanwhile, the cleavage by gamma-cleavage of the transmembrane domain of APP was abolished. A 5-fold drop of amyloid peptide was observed, suggesting that deficiency of presenilin-1 can down regulate amyloid and inhibition of presenilin-1 can be a potential method for anti-amyloidogenic therapy in Alzheimer's disease.[19] Extensive study on the role of presenilin-1 in amyloid production has been conducted to improve our understanding of Alzheimer's disease.[20][21]
## Alzheimer's disease
Alzheimer's disease (AD) patients with an inherited form of the disease may carry mutations in the presenilin proteins (PSEN1; PSEN2) or the amyloid precursor protein (APP). These disease-linked mutations result in increased production of the longer form of amyloid beta (main component of amyloid deposits found in AD brains). These mutations result in early-onset Alzheimer's Disease, which is a rare form of the disease. These rare genetic variants are autosomal dominant.[22]
## Cancer
In addition to its role in Alzheimer's disease, presenilin-1 also found to be important in cancer. A study of broad range gene expression was conducted on human malignant melanoma. Researchers classified the malignant melanoma cell lines into two types. The study showed that presenilin-1 is down regulated in cell type while it is overexpressed in the other cell type.[23] Another study on multidrug resistance (MDR) cell line also reveals a role of presenilin-1 in cancer development. Because of the development to the resistance to chemical, MDR cells become a critical factor on the success of cancer chemotherapy.[24] In the study, researchers tried to explore the molecular mechanism by looking into the expression of Notch1 intracellular (N1IC) domain and presenilin 1. They found that there is higher level expression of both proteins and a multidrug resistance-associated protein 1 (ABCC1) was also found to be regulated by N1IC, which suggest a mechanism of ABCC1 regulated by presenilin 1 and notch signaling.[25]
# Interactions
PSEN1 has been shown to interact with:
- BCL2,[26]
- CTNNB1,[27][28][29]
- CTNND1,[30]
- FLNB,[31]
- GFAP,[32]
- Delta catenin,[33]
- ICAM5,[34]
- KCNIP3,[35][36]
- NCSTN,[37][38][39][40][41]
- PKP4,[42] and
- UBQLN1.[43] | https://www.wikidoc.org/index.php/Alzheimer_disease_3 | |
5552d1fdb844de52f22362990cfa62a6a5b150ef | wikidoc | Amber | Amber
Amber is the name for fossil resin or tree sap that is appreciated for its colour. It is used for the manufacture of ornamental objects and jewellery. Although not mineralized, it is sometimes considered a gemstone. Most of the world's amber is in the range of 30–90 million years old. Semi-fossilized resin or sub-fossil amber is called copal. It can hold insects or even small mammals.
# Origin of the term
The English word amber stems from the old Arabic word anbargris or ambergris and refers to an oily, perfumed substance secreted by the sperm whale. Middle English ambre > Old French ambre > Medieval Latin ambra (or ambar). It floats on water and is washed up on the beaches. Due to a confusion of terms (see: Abu Zaid al Hassan from Siraf & Sulaiman the Merchant (851), Silsilat-al-Tawarikh (travels in Asia), it became to be the name for fossil resin or tree sap, which is also found on beaches.
The presence of insects in amber was noticed by the Romans and led them to the (correct) theory that at some point, amber had to be in a liquid state to cover the bodies of insects. Hence they gave it the expressive name of suceinum or gum-stone, a name that is still in use today to describe succinic acid as well as succinite, a term given to a particular type of amber by James Dwight Dana (see below under Baltic Amber). The Greek name for amber was ηλεκτρον (Electron) and was connected to the Sun God, one of whose titles was Elector or the Awakener.
The modern term electron was coined in 1891 by the Irish physicist George Stoney, using the Greek word for amber (and which was then translated as electrum) because of its electrostatic properties and whilst analyzing elementary charge for the first time. The ending -on, common for all subatomic particles, was used in analogy to the word ion.
Heating amber will soften it and eventually it will burn, which is why in Germanic languages the word for amber is a literal translation of burn-Stone (In German it is Bernstein, in Dutch it is barnsteen etc.). Heated below 200°C, amber suffers decomposition, yielding an "oil of amber", and leaving a black residue which is known as "amber colophony", or "amber pitch"; when dissolved in oil of turpentine or in linseed oil this forms "amber varnish" or "amber lac".
# Chemistry of amber
Amber is heterogeneous in composition, but consists of several resinous bodies more or less soluble in alcohol, ether and chloroform, associated with an insoluble bituminous substance. Amber is a macromolecule by free radical polymerization of several precursors in the labdane family, communic acid, cummunol and biformene. These labdanes are diterpenes (C20H32) and trienes which means that the organic skeleton has three alkene groups available for polymerization. As amber matures over the years, more polymerization will take place as well as isomerization reactions, crosslinking and cyclization. The average composition of amber leads to the general formula C10H16O.
Amber should be distinguished from copal. Molecular polymerisation caused by pressure and heat transforms the resin first into copal and then over time through the evaporation of turpenes it is transformed into amber.
Baltic amber is distinguished from the various other ambers from around the world, by the presence within it of succinic acid, hence Baltic amber is otherwise known as succinite.
# Amber in geology
The oldest amber originates from the Upper Carboniferous period approximately 345 million years ago. The oldest known amber containing insects comes from the Lower Cretaceous, approximately 146 million years ago).
Commercially most important are the deposits of Baltic and Dominican amber. They both are of tertiary age (40-50 Ma respectively 25-40 Ma).
Baltic amber or succinite (historically documented as Prussian amber) is found as irregular nodules in a marine glauconitic sand, known as blue earth, occurring in the Lower Oligocene strata of Sambia in Kaliningrad Oblast, where it is now systematically mined. It appears, however, to have been partly derived from yet earlier Tertiary deposits (Eocene); and it occurs also as a derivative mineral in later formations, such as the drift. Relics of an abundant flora occur as inclusions trapped within the amber while the resin was yet fresh, suggesting relations with the flora of Eastern Asia and the southern part of North America. Heinrich Göppert named the common amber-yielding pine of the Baltic forests Pinites succiniter, but as the wood, according to some authorities, does not seem to differ from that of the existing genus it has been also called Pinus succinifera. It is improbable, however, that the production of amber was limited to a single species; and indeed a large number of conifers belonging to different genera are represented in the amber-flora.
Dominican amber is considered retinite, since it has no succinic acid. There are three main sites in the Dominican Republic: La Cordillera Septentrional, in the north, Bayaguana and Sabana, in the east. In the northern area, the amber-bearing unit is formed of clastic rocks, sandstone accumulated in a deltaic or even deep-water environment. The oldest, and hardest of this amber comes from the mountain region north of Santiago area, from the mines at La Cumbre, La Toca, Palo Quemado, La Bucara, and Los Cacaos mining sites in the Cordillera Septentrional not far from Santiago. Amber in these mountains is tightly embedded in a lignite layer of sandstone.
There is also amber in the south-eastern Bayaguana/Sabana area. It is softer, sometimes brittle and suffers
-xidation after being taken from the mines, therefore less expensive. There is also copal found with only an age of 15-17 million years. In the eastern area, the amber is found in a sediment formation of organic-rich laminated sand, sandy clay, intercalated lignite as well as some solated beds of gravel and calcarenite.
Both, Baltic and Dominican amber, are rich sources of fossils and give much information about life in the ancient forests.
Amber from the Middle Cretaceous is known from Ellsworth County, Kansas. This approximately 100 million year old amber has inclusions of bacteria and amoebae. They are morphologically very close to Leptothrix, and the modern genera Pontigulasia and Nebela. Morphological stasis is considered to be confirmed.
# Amber inclusions
The resin contains, in addition to the beautifully preserved plant-structures, numerous remains of insects, spiders, annelids, frogs, crustaceans and other small organisms which were trapped by the sticky surface and became enveloped while the exudation was fluid. In most cases the organic structure has disappeared, leaving only a cavity, with perhaps a trace of chitin. Even hair and feathers have occasionally been represented among the enclosures. Fragments of wood frequently occur, with the tissues well-preserved by impregnation with the resin; while leaves, flowers and fruits are occasionally found in marvelous perfection. Sometimes the amber retains the form of drops and stalactites, just as it exuded from the ducts and receptacles of the injured trees. It is thought that, in addition to exuding onto the surface of the tree, amber resin also originally flowed into hollow cavities or cracks within trees, thereby leading to the development of large lumps of amber of irregular form. The abnormal development of resin has been called succinosis. Impurities are quite often present, especially when the resin dropped on to the ground, so that the material may be useless except for varnish-making, whence the impure amber is called firniss. Enclosures of pyrites may give a bluish colour to amber. The so-called black amber is only a kind of jet. Bony amber owes its cloudy opacity to minute bubbles in the interior of the resin.
Not all amber is translucent, becoming transparent when the surfaces are polished, thus revealing inclusions. The technique of inspecting darkly clouded and even opaque amber for inclusions, through bombarding it with high-energy, high-contrast, high-resolution x-rays, is being developed at the European Synchrotron Radiation Facility. Nearly 360 fossil invertebrates have been discovered from opaque amber found at Charentes, France: primitive wasps, flies, ants and spiders, particularly those measuring just a few millimeters. Three-dimensional images of the trapped organisms are built up through microtomography, showing detail on the scales of microns. An enlarged plastic three-dimensional model can be obtained of an organism that has remained embedded in the amber, suggesting alternative means of cataloguing new species trapped in amber.
# Amber locations
## Baltic amber
Baltic amber has a very wide distribution, extending over a large part of northern Europe and occurring as far east as the Urals.
Baltic amber yields on dry distillation succinic acid, the proportion varying from about 3% to 8%, and being greatest in the pale opaque or bony varieties. The aromatic and irritating fumes emitted by burning amber are mainly due to this acid. Baltic amber is distinguished by its yield of succinic acid, hence the name succinite proposed by Professor James Dwight Dana, and now commonly used in scientific writings as a specific term for the Prussian amber. Succinite has a hardness between 2 and 3, which is rather greater than that of many other fossil resins. Its specific gravity varies from 1.05 to 1.10. An effective tool for Baltic amber analysis is IR spectroscopy. It enables the distinction between Baltic and non-Baltic amber varieties because of a specific carbonyl absorption and it can also detect the relative age of an amber sample. On the other hand, it has been suggested by scientists that succinic acid is no original component of amber, but a degradation product of abietic acid. (Rottlaender, 1970)
Although amber is found along the shores of a large part of the Baltic Sea and the North Sea, the great amber-producing country is the promontory of Sambia, now part of Russia. About 90% of the world's extractable amber is located in the Kaliningrad region of Russia on the Baltic Sea. Pieces of amber torn from the seafloor are cast up by the waves, and collected at ebb-tide. Sometimes the searchers wade into the sea, furnished with nets at the end of long poles, which they drag in the sea-weed containing entangled masses of amber; or they dredge from boats in shallow water and rake up amber from between the boulders. Divers have been employed to collect amber from the deeper waters. Systematic dredging on a large scale was at one time carried on in the Curonian Lagoon by Messrs Stantien and Becker, the great amber merchants of Königsberg. At the present time extensive mining operations are conducted in quest of amber. The pit amber was formerly dug in open works, but is now also worked by underground galleries. The nodules from the blue earth have to be freed from matrix and divested of their opaque crust, which can be done in revolving barrels containing sand and water. The sea-worn amber has lost its crust, but has often acquired a dull rough surface by rolling in sand.
Since the establishment of the Amber Road, amber (which is also commonly referred to as the "Lithuanian gold") has substantially contributed to Lithuanian economy and culture. Nowadays a great variety of amber jewelry and amberware is offered to foreign tourists in most souvenir shops as distinctive to Lithuania and its cultural heritage. The Amber Museum containing unique specimen of amber has been established in Palanga, near the sea coast. Amber can also be found in Latvia.
## Dominican Amber
Since the book and movie Jurassic Park, Dominican amber has become world famous. Dominican amber differentiates itself from Baltic amber by being mostly transparent, and has a higher number of fossil inclusions. This has enabled the detailed reconstruction of the ecosystem of a long-vanished tropical forest. Resin from the extinct species Hymenaea protera is the source of Dominican amber and probably of most amber found in the tropics. It is not "succinite" but "retinite". In contrast to much Baltic amber, Dominican amber found on the world market is natural amber the way it comes from the mines, and has not been enhanced or received any chemical or physical change. The age of Dominican amber is around 40 Million years.
Although all Dominican amber is fluorescent up to a certain degree, the rarest Dominican Amber is Blue amber. It turns blue in natural sunlight and any other light source that has a slight component of UV (Ultra Violet). In long-wave UV light it has a very strong reflection, almost white. Only about approximately 100 kilos of this fossilized tree resin are found per year, which makes it valuable and expensive.
Dominican Amber, and especially Dominican blue amber is mined through bell pitting, which is extremely dangerous. Bell pitting (bell pit) is basically a foxhole dug with whatever tools are available. Machetes do the start, some shovels, picks and hammers may participate eventually. The pit itself goes as deep as possible or safe, sometimes vertical, sometimes horizontal, but never level. It snakes into hill sides, drops away, joins up with others, goes straight up and pops out elsewhere. 'Foxhole' applies indeed: rarely are the pits large enough to stand in, and then only at the entrance. Miners crawl around on their knees using short-handled picks, shovels and machetes. There are little to no safety measures. A pillar or so may hold back the ceiling from time to time but only if the area has previously collapsed. Candles are the only source of light. Humidity inside the mines is at 100%. Since the holes are situated high on mountainsides and deep inside said mountains, the temperature is cool and bearable, but after several hours the air becomes stale. During rain the mines are forced to close. The holes fill up quickly with water, and there is little point in pumping it out again (although sometimes this is done) because the unsecured walls may crumble. The amber that is found is either directly sold as rough or raw pieces or cut and polished without any additional treatments or enhancements.
The most common use for Dominican Amber is as ornaments and jewelry, while the more valuable enclosures and colorations become priced exhibition pieces both in private and public collections. In Far East, Blue Amber has been masterfully worked into artistic carvings. Others have used Blue Amber to make jewelry that can be especially attractive for its natural fluorescence under UV lights. In the Muslim world Dominican Amber and particularly Blue Amber beads have found their way into another use as worry beads, since Dominican Amber can very easily be worked.
## Other locations
Amber deposits are found around the world. Some are much older than the well known amber deposits in the Baltic countries and the Dominican Republic, other are much younger. Some Amber is considered to be up to 345,000,000 years old (Northumberland USA).
A lesser known source of amber is in the Ukraine, within a marshy forested area on the Volyhn-Polesie border. Due to the shallow depth that this amber is found at it can be extracted with the simplest of tools, and has hence led to an economy of 'amber poaching' under cover of the forest. This Ukrainian amber is much appreciated for its wide range of colours, and was used in the restoration of 'amber room' in the Empress Catherines palace in St Petersberg (see below).
Rolled pieces of amber, usually small but occasionally of very large size, may be picked up on the east coast of England, having probably been washed up from deposits under the North Sea. Cromer is the best-known locality, but it occurs also on other parts of the Norfolk coast, such as Great Yarmouth, as well as Southwold, Aldeburgh and Felixstowe in Suffolk, and as far south as Walton-on-the-Naze in Essex, whilst northwards it is not unknown in Yorkshire. On the other side of the North Sea, amber is found at various localities on the coast of the Netherlands and Denmark. On the shores of the Baltic it occurs not only on the German and Polish coast but in the south of Sweden, in Bornholm and other islands, and in southern Finland. Some of the amber districts of the Baltic and North Sea were known in prehistoric times, and led to early trade with the south of Europe through the Amber Road. Amber was carried to Olbia on the Black Sea, Massilia (today Marseille) on the Mediterranean, and Adria at the head of the Adriatic; and from these centres it was distributed over the Ancient Greek world.
Both in Switzerland and in Austria and France are amber deposits. Amber from the Swiss Alps is about 55 - 200 million years old, amber from Golling about 225 - 231 million years. The well-known SicilianAmber(Simetit - copal) is just 10 - 20 million years old.
In Africa, copal is found in the coastal countries of East and West Africa, but especially on Madagascar. This so-called Madagascar Amber is only 1,000 - 10,000 years old and consists of the solidified resin of the amber pine. Nigeria also has amber, which is about 60 million years old.
In Asia amber can be found especially in Burma (former Burma / Myanmar) as Burmit. It is about 50 million years and the Lebanon amber 130 - 135 million years old. Amber of the Australian-oceanic area can be found in New Zealand and Borneo (Sawak amber). They are about 20 - 60, part 70 - 100 million years old.
The oldest amber are sporadically from the Devon.
Amber is also found to a limited extent at several localities in the United States, as in the green-sand of New Jersey, but they have little or no economic value. Middle Cretaceous amber has also been found in Ellsworth county, Kansas. It has little value for jewelry makers, but is very valuable to biologists. Unfortunately the source of this amber is currently under a man made lake.
A fluorescent amber occurs also in the southern state of Chiapas in Mexico, and is used extensively to create eye-catching jewelery. In Central America, the Olmec civilization also was mining amber around 3000 B.C. There are legends in Mexico that mention the use of amber in adorning, consuming and using it for stress reduction as a natural remedy.
Indonesia is also a rich source of amber with large fragments being unearthed in both Java and Bali.
# Amber treatments
The famous Vienna amber factories which use pale amber to manufacture pipes and other smoking tools, apply a specific procedure when working amber: it is turned on the lathe and polished with whitening and water or with rotten stone and oil, the final lustre being given by friction with flannel. During the working a significant electrostatic charge is developed.
When gradually heated in an oil-bath, amber becomes soft and flexible. Two pieces of amber may be united by smearing the surfaces with linseed oil, heating them, and then pressing them together while hot. Cloudy amber may be clarified in an oil-bath, as the oil fills the numerous pores to which the turbidity is due. Small fragments, formerly thrown away or used only for varnish, are now utilized on a large scale in the formation of "ambroid" or "pressed amber". The pieces are carefully heated with exclusion of air and then compressed into a uniform mass by intense hydraulic pressure; the softened amber being forced through holes in a metal plate. The product is extensively used for the production of cheap jewelery and articles for smoking. This pressed amber yields brilliant interference colors in polarized light. Amber has often been imitated by other resins like copal and kauri, as well as by celluloid and even glass. Baltic amber is sometimes colored artificially, but also called "true amber".
Often amber (particularly with insect inclusions) is counterfeited using a plastic resin similar in appearance. A simple test (performed on the back of the object) consists of touching the object with a heated pin and determining if the resultant odor is of wood resin. If not, the object is counterfeit, although a positive test may not be conclusive owing to a thin coat of real resin. Often counterfeits will have a too perfect pose and position of the trapped insect.
# Amber art and ornament
Amber was much valued as an ornamental material in very early times. It has been found in Mycenaean tombs; it is known from lake-dwellings in Switzerland, and it occurs with Neolithic remains in Denmark, whilst in England it is found with interments of the bronze age. A remarkably fine cup turned in amber from a bronze-age barrow at Hove is now in the Brighton Museum. Beads of amber occur with Anglo-Saxon relics in the south of England; and up to a comparatively recent period the material was valued as an amulet. It is still believed to possess a certain medicinal virtue.
Amber is extensively used for beads and other ornaments, and for cigar-holders and the mouth-pieces of pipes. It is regarded by the Turks as specially valuable, inasmuch as it is said to be incapable of transmitting infection as the pipe passes from mouth to mouth. The variety most valued in the East is the pale straw-colored, slightly cloudy amber. Some of the best qualities are sent to Vienna for the manufacture of smoking appliances.
The Amber Room was a collection of chamber wall panels commissioned in 1701 for the king of Prussia, then given to Tsar Peter the Great. The room was hidden in place from invading Nazi forces in 1941, who upon finding it in the Catherine Palace, disassembled it and moved it to Königsberg. What happened to the room beyond this point is unclear, but it may have been destroyed when the Russians burned the German fortification where it was stored. It is presumed lost. It was re-created in 2003.
Amber has also been used to create the "frog" part of a Violin bow. It was commissioned by Gennady Filimonov and made by the late American Master Bowmaker Keith Peck | Amber
Amber is the name for fossil resin or tree sap that is appreciated for its colour. It is used for the manufacture of ornamental objects and jewellery. Although not mineralized, it is sometimes considered a gemstone. Most of the world's amber is in the range of 30–90 million years old. Semi-fossilized resin or sub-fossil amber is called copal. It can hold insects or even small mammals.
# Origin of the term
The English word amber stems from the old Arabic word anbargris or ambergris and refers to an oily, perfumed substance secreted by the sperm whale. Middle English ambre > Old French ambre > Medieval Latin ambra (or ambar). It floats on water and is washed up on the beaches. Due to a confusion of terms (see: Abu Zaid al Hassan from Siraf & Sulaiman the Merchant (851), Silsilat-al-Tawarikh (travels in Asia), it became to be the name for fossil resin or tree sap, which is also found on beaches.
The presence of insects in amber was noticed by the Romans and led them to the (correct) theory that at some point, amber had to be in a liquid state to cover the bodies of insects. Hence they gave it the expressive name of suceinum or gum-stone, a name that is still in use today to describe succinic acid as well as succinite, a term given to a particular type of amber by James Dwight Dana (see below under Baltic Amber). The Greek name for amber was ηλεκτρον (Electron) and was connected to the Sun God, one of whose titles was Elector or the Awakener.[1]
The modern term electron was coined in 1891 by the Irish physicist George Stoney, using the Greek word for amber (and which was then translated as electrum) because of its electrostatic properties and whilst analyzing elementary charge for the first time. The ending -on, common for all subatomic particles, was used in analogy to the word ion.[2][3]
Heating amber will soften it and eventually it will burn, which is why in Germanic languages the word for amber is a literal translation of burn-Stone (In German it is Bernstein, in Dutch it is barnsteen etc.). Heated below 200°C, amber suffers decomposition, yielding an "oil of amber", and leaving a black residue which is known as "amber colophony", or "amber pitch"; when dissolved in oil of turpentine or in linseed oil this forms "amber varnish" or "amber lac".
# Chemistry of amber
Amber is heterogeneous in composition, but consists of several resinous bodies more or less soluble in alcohol, ether and chloroform, associated with an insoluble bituminous substance. Amber is a macromolecule by free radical polymerization of several precursors in the labdane family, communic acid, cummunol and biformene.[4] These labdanes are diterpenes (C20H32) and trienes which means that the organic skeleton has three alkene groups available for polymerization. As amber matures over the years, more polymerization will take place as well as isomerization reactions, crosslinking and cyclization. The average composition of amber leads to the general formula C10H16O.
Amber should be distinguished from copal. Molecular polymerisation caused by pressure and heat transforms the resin first into copal and then over time through the evaporation of turpenes it is transformed into amber.
Baltic amber is distinguished from the various other ambers from around the world, by the presence within it of succinic acid,[citation needed] hence Baltic amber is otherwise known as succinite.
# Amber in geology
The oldest amber originates from the Upper Carboniferous period approximately 345 million years ago. The oldest known amber containing insects comes from the Lower Cretaceous, approximately 146 million years ago).
Commercially most important are the deposits of Baltic and Dominican amber. They both are of tertiary age (40-50 Ma respectively 25-40 Ma).[5]
Baltic amber or succinite (historically documented as Prussian amber) is found as irregular nodules in a marine glauconitic sand, known as blue earth, occurring in the Lower Oligocene strata of Sambia in Kaliningrad Oblast, where it is now systematically mined.[6] It appears, however, to have been partly derived from yet earlier Tertiary deposits (Eocene); and it occurs also as a derivative mineral in later formations, such as the drift. Relics of an abundant flora occur as inclusions trapped within the amber while the resin was yet fresh, suggesting relations with the flora of Eastern Asia and the southern part of North America. Heinrich Göppert named the common amber-yielding pine of the Baltic forests Pinites succiniter, but as the wood, according to some authorities, does not seem to differ from that of the existing genus it has been also called Pinus succinifera. It is improbable, however, that the production of amber was limited to a single species; and indeed a large number of conifers belonging to different genera are represented in the amber-flora.
Dominican amber is considered retinite, since it has no succinic acid. There are three main sites in the Dominican Republic: La Cordillera Septentrional, in the north, Bayaguana and Sabana, in the east. In the northern area, the amber-bearing unit is formed of clastic rocks, sandstone accumulated in a deltaic or even deep-water environment. The oldest, and hardest of this amber comes from the mountain region north of Santiago area, from the mines at La Cumbre, La Toca, Palo Quemado, La Bucara, and Los Cacaos mining sites in the Cordillera Septentrional not far from Santiago. Amber in these mountains is tightly embedded in a lignite layer of sandstone.
There is also amber in the south-eastern Bayaguana/Sabana area. It is softer, sometimes brittle and suffers
oxidation after being taken from the mines, therefore less expensive. There is also copal found with only an age of 15-17 million years. In the eastern area, the amber is found in a sediment formation of organic-rich laminated sand, sandy clay, intercalated lignite as well as some solated beds of gravel and calcarenite.
Both, Baltic and Dominican amber, are rich sources of fossils and give much information about life in the ancient forests. [7]
Amber from the Middle Cretaceous is known from Ellsworth County, Kansas. This approximately 100 million year old amber has inclusions of bacteria and amoebae. They are morphologically very close to Leptothrix, and the modern genera Pontigulasia and Nebela. Morphological stasis is considered to be confirmed.[8]
# Amber inclusions
The resin contains, in addition to the beautifully preserved plant-structures, numerous remains of insects, spiders, annelids, frogs,[9] crustaceans and other small organisms which were trapped by the sticky surface and became enveloped while the exudation was fluid. In most cases the organic structure has disappeared, leaving only a cavity, with perhaps a trace of chitin. Even hair and feathers have occasionally been represented among the enclosures. Fragments of wood frequently occur, with the tissues well-preserved by impregnation with the resin; while leaves, flowers and fruits are occasionally found in marvelous perfection. Sometimes the amber retains the form of drops and stalactites, just as it exuded from the ducts and receptacles of the injured trees. It is thought that, in addition to exuding onto the surface of the tree, amber resin also originally flowed into hollow cavities or cracks within trees, thereby leading to the development of large lumps of amber of irregular form.[10] The abnormal development of resin has been called succinosis. Impurities are quite often present, especially when the resin dropped on to the ground, so that the material may be useless except for varnish-making, whence the impure amber is called firniss. Enclosures of pyrites may give a bluish colour to amber. The so-called black amber is only a kind of jet. Bony amber owes its cloudy opacity to minute bubbles in the interior of the resin.
Not all amber is translucent, becoming transparent when the surfaces are polished, thus revealing inclusions. The technique of inspecting darkly clouded and even opaque amber for inclusions, through bombarding it with high-energy, high-contrast, high-resolution x-rays, is being developed at the European Synchrotron Radiation Facility.[11] Nearly 360 fossil invertebrates have been discovered from opaque amber found at Charentes, France: primitive wasps, flies, ants and spiders, particularly those measuring just a few millimeters. Three-dimensional images of the trapped organisms are built up through microtomography, showing detail on the scales of microns. An enlarged plastic three-dimensional model can be obtained of an organism that has remained embedded in the amber, suggesting alternative means of cataloguing new species trapped in amber.
# Amber locations
## Baltic amber
Baltic amber has a very wide distribution, extending over a large part of northern Europe and occurring as far east as the Urals.
Baltic amber yields on dry distillation succinic acid, the proportion varying from about 3% to 8%, and being greatest in the pale opaque or bony varieties. The aromatic and irritating fumes emitted by burning amber are mainly due to this acid. Baltic amber is distinguished by its yield of succinic acid, hence the name succinite proposed by Professor James Dwight Dana, and now commonly used in scientific writings as a specific term for the Prussian amber. Succinite has a hardness between 2 and 3, which is rather greater than that of many other fossil resins. Its specific gravity varies from 1.05 to 1.10. An effective tool for Baltic amber analysis is IR spectroscopy. It enables the distinction between Baltic and non-Baltic amber varieties because of a specific carbonyl absorption and it can also detect the relative age of an amber sample. On the other hand, it has been suggested by scientists that succinic acid is no original component of amber, but a degradation product of abietic acid. (Rottlaender, 1970)
Although amber is found along the shores of a large part of the Baltic Sea and the North Sea, the great amber-producing country is the promontory of Sambia, now part of Russia. About 90% of the world's extractable amber is located in the Kaliningrad region of Russia on the Baltic Sea.[12] Pieces of amber torn from the seafloor are cast up by the waves, and collected at ebb-tide. Sometimes the searchers wade into the sea, furnished with nets at the end of long poles, which they drag in the sea-weed containing entangled masses of amber; or they dredge from boats in shallow water and rake up amber from between the boulders. Divers have been employed to collect amber from the deeper waters. Systematic dredging on a large scale was at one time carried on in the Curonian Lagoon by Messrs Stantien and Becker, the great amber merchants of Königsberg. At the present time extensive mining operations are conducted in quest of amber. The pit amber was formerly dug in open works, but is now also worked by underground galleries. The nodules from the blue earth have to be freed from matrix and divested of their opaque crust, which can be done in revolving barrels containing sand and water. The sea-worn amber has lost its crust, but has often acquired a dull rough surface by rolling in sand.
Since the establishment of the Amber Road, amber (which is also commonly referred to as the "Lithuanian gold") has substantially contributed to Lithuanian economy and culture. Nowadays a great variety of amber jewelry and amberware is offered to foreign tourists in most souvenir shops as distinctive to Lithuania and its cultural heritage. The Amber Museum containing unique specimen of amber has been established in Palanga, near the sea coast. Amber can also be found in Latvia.
## Dominican Amber
Since the book and movie Jurassic Park, Dominican amber has become world famous. Dominican amber differentiates itself from Baltic amber by being mostly transparent, and has a higher number of fossil inclusions. This has enabled the detailed reconstruction of the ecosystem of a long-vanished tropical forest.[13] Resin from the extinct species Hymenaea protera is the source of Dominican amber and probably of most amber found in the tropics. It is not "succinite" but "retinite". [14]In contrast to much Baltic amber, Dominican amber found on the world market is natural amber the way it comes from the mines, and has not been enhanced or received any chemical or physical change. The age of Dominican amber is around 40 Million years. [15]
Although all Dominican amber is fluorescent up to a certain degree, the rarest Dominican Amber is Blue amber. It turns blue in natural sunlight and any other light source that has a slight component of UV (Ultra Violet). In long-wave UV light it has a very strong reflection, almost white. Only about approximately 100 kilos of this fossilized tree resin are found per year, which makes it valuable and expensive.[16]
Dominican Amber, and especially Dominican blue amber is mined through bell pitting, which is extremely dangerous. [17]Bell pitting (bell pit) is basically a foxhole dug with whatever tools are available. Machetes do the start, some shovels, picks and hammers may participate eventually. The pit itself goes as deep as possible or safe, sometimes vertical, sometimes horizontal, but never level. It snakes into hill sides, drops away, joins up with others, goes straight up and pops out elsewhere. 'Foxhole' applies indeed: rarely are the pits large enough to stand in, and then only at the entrance. Miners crawl around on their knees using short-handled picks, shovels and machetes. There are little to no safety measures. A pillar or so may hold back the ceiling from time to time but only if the area has previously collapsed. Candles are the only source of light. Humidity inside the mines is at 100%. Since the holes are situated high on mountainsides and deep inside said mountains, the temperature is cool and bearable, but after several hours the air becomes stale. During rain the mines are forced to close. The holes fill up quickly with water, and there is little point in pumping it out again (although sometimes this is done) because the unsecured walls may crumble. The amber that is found is either directly sold as rough or raw pieces or cut and polished without any additional treatments or enhancements.[13]
The most common use for Dominican Amber is as ornaments and jewelry, while the more valuable enclosures and colorations become priced exhibition pieces both in private and public collections. [18]In Far East, Blue Amber has been masterfully worked into artistic carvings. Others have used Blue Amber to make jewelry that can be especially attractive for its natural fluorescence under UV lights. In the Muslim world Dominican Amber and particularly Blue Amber beads have found their way into another use as worry beads, since Dominican Amber can very easily be worked.[19][20]
## Other locations
Amber deposits are found around the world. Some are much older than the well known amber deposits in the Baltic countries and the Dominican Republic, other are much younger. Some Amber is considered to be up to 345,000,000 years old (Northumberland USA).
A lesser known source of amber is in the Ukraine, within a marshy forested area on the Volyhn-Polesie border. Due to the shallow depth that this amber is found at it can be extracted with the simplest of tools, and has hence led to an economy of 'amber poaching' under cover of the forest. This Ukrainian amber is much appreciated for its wide range of colours, and was used in the restoration of 'amber room' in the Empress Catherines palace in St Petersberg (see below).
Rolled pieces of amber, usually small but occasionally of very large size, may be picked up on the east coast of England, having probably been washed up from deposits under the North Sea. Cromer is the best-known locality, but it occurs also on other parts of the Norfolk coast, such as Great Yarmouth, as well as Southwold, Aldeburgh and Felixstowe in Suffolk, and as far south as Walton-on-the-Naze in Essex, whilst northwards it is not unknown in Yorkshire. On the other side of the North Sea, amber is found at various localities on the coast of the Netherlands and Denmark. On the shores of the Baltic it occurs not only on the German and Polish coast but in the south of Sweden, in Bornholm and other islands, and in southern Finland. Some of the amber districts of the Baltic and North Sea were known in prehistoric times, and led to early trade with the south of Europe through the Amber Road. Amber was carried to Olbia on the Black Sea, Massilia (today Marseille) on the Mediterranean, and Adria at the head of the Adriatic; and from these centres it was distributed over the Ancient Greek world.
Both in Switzerland and in Austria and France are amber deposits. Amber from the Swiss Alps is about 55 - 200 million years old, amber from Golling about 225 - 231 million years. The well-known SicilianAmber(Simetit - copal) is just 10 - 20 million years old.
In Africa, copal is found in the coastal countries of East and West Africa, but especially on Madagascar. This so-called Madagascar Amber is only 1,000 - 10,000 years old and consists of the solidified resin of the amber pine. Nigeria also has amber, which is about 60 million years old.
In Asia amber can be found especially in Burma (former Burma / Myanmar) as Burmit. It is about 50 million years and the Lebanon amber 130 - 135 million years old. Amber of the Australian-oceanic area can be found in New Zealand and Borneo (Sawak amber). They are about 20 - 60, part 70 - 100 million years old.
The oldest amber are sporadically from the Devon.
Amber is also found to a limited extent at several localities in the United States, as in the green-sand of New Jersey, but they have little or no economic value. Middle Cretaceous amber has also been found in Ellsworth county, Kansas. It has little value for jewelry makers, but is very valuable to biologists. Unfortunately the source of this amber is currently under a man made lake.
A fluorescent amber occurs also in the southern state of Chiapas in Mexico, and is used extensively to create eye-catching jewelery. In Central America, the Olmec civilization also was mining amber around 3000 B.C. There are legends in Mexico that mention the use of amber in adorning, consuming and using it for stress reduction as a natural remedy.
Indonesia is also a rich source of amber with large fragments being unearthed in both Java and Bali.
# Amber treatments
The famous Vienna amber factories which use pale amber to manufacture pipes and other smoking tools, apply a specific procedure when working amber: it is turned on the lathe and polished with whitening and water or with rotten stone and oil, the final lustre being given by friction with flannel. During the working a significant electrostatic charge is developed.
When gradually heated in an oil-bath, amber becomes soft and flexible. Two pieces of amber may be united by smearing the surfaces with linseed oil, heating them, and then pressing them together while hot. Cloudy amber may be clarified in an oil-bath, as the oil fills the numerous pores to which the turbidity is due. Small fragments, formerly thrown away or used only for varnish, are now utilized on a large scale in the formation of "ambroid" or "pressed amber". The pieces are carefully heated with exclusion of air and then compressed into a uniform mass by intense hydraulic pressure; the softened amber being forced through holes in a metal plate. The product is extensively used for the production of cheap jewelery and articles for smoking. This pressed amber yields brilliant interference colors in polarized light. Amber has often been imitated by other resins like copal and kauri, as well as by celluloid and even glass. Baltic amber is sometimes colored artificially, but also called "true amber".
Often amber (particularly with insect inclusions) is counterfeited using a plastic resin similar in appearance. A simple test (performed on the back of the object) consists of touching the object with a heated pin and determining if the resultant odor is of wood resin. If not, the object is counterfeit, although a positive test may not be conclusive owing to a thin coat of real resin. Often counterfeits will have a too perfect pose and position of the trapped insect.
# Amber art and ornament
Amber was much valued as an ornamental material in very early times. It has been found in Mycenaean tombs; it is known from lake-dwellings in Switzerland, and it occurs with Neolithic remains in Denmark, whilst in England it is found with interments of the bronze age. A remarkably fine cup turned in amber from a bronze-age barrow at Hove is now in the Brighton Museum. Beads of amber occur with Anglo-Saxon relics in the south of England; and up to a comparatively recent period the material was valued as an amulet. It is still believed to possess a certain medicinal virtue.
Amber is extensively used for beads and other ornaments, and for cigar-holders and the mouth-pieces of pipes. It is regarded by the Turks as specially valuable, inasmuch as it is said to be incapable of transmitting infection as the pipe passes from mouth to mouth. The variety most valued in the East is the pale straw-colored, slightly cloudy amber. Some of the best qualities are sent to Vienna for the manufacture of smoking appliances.
The Amber Room was a collection of chamber wall panels commissioned in 1701 for the king of Prussia, then given to Tsar Peter the Great. The room was hidden in place from invading Nazi forces in 1941, who upon finding it in the Catherine Palace, disassembled it and moved it to Königsberg. What happened to the room beyond this point is unclear, but it may have been destroyed when the Russians burned the German fortification where it was stored. It is presumed lost. It was re-created in 2003.[21]
Amber has also been used to create the "frog" part of a Violin bow. It was commissioned by Gennady Filimonov and made by the late American Master Bowmaker Keith Peck
[22] | https://www.wikidoc.org/index.php/Amber | |
fef68c51d324b6f15d3d6e4f1a3495f5b5793459 | wikidoc | Amide | Amide
In chemistry, an amide is one of two kinds of compounds:
- the organic functional group characterized by a carbonyl group (C=O) linked to a nitrogen atom (N), or a compound that contains this functional group (pictured to the right); or
- a particular kind of nitrogen anion.
Amides are the most stable of all the carbonyl functional groups.
Many chemists make a pronunciation distinction between the two, saying (Template:IPA2 for the carbonyl-nitrogen compound and for the anion. Others substitute one of these pronunciations with , while still others pronounce both as , making them homonyms.
In the first sense referred to above, an amide is an amine where one of the nitrogen substituents is an acyl group; it is generally represented by the formula: R1(CO)NR2R3 , where either or both R2 and R3 may be hydrogen. Specifically, an amide can also be regarded as a derivative of a carboxylic acid in which the hydroxyl group has been replaced by an amine or ammonia.
Compounds in which a hydrogen atom on nitrogen from ammonia or an amine is replaced by a metal cation are also known as amides or azanides.
The second sense of the word amide is the amide anion, which is a deprotonated form of ammonia (NH3) or an amine. It is generally represented by the formula: -, and is an extremely strong base, due to the extreme weakness of ammonia and its analogues as Brønsted acids.
The remainder of this article is about the carbonyl-nitrogen sense of amide. For examples of the anionic amide, see the articles Sodium amide and Lithium diisopropylamide.
# Amide synthesis
- Amides are commonly formed from the reaction of a carboxylic acid with an amine. This is the reaction that forms peptide bonds between amino acids. These amides can participate in hydrogen bonding as hydrogen bond acceptors and donors, but do not ionize in aqueous solution, whereas their parent acids and amines are almost completely ionized in solution at neutral pH. Amide formation plays a role in the synthesis of some condensation polymers, such as nylon and Aramid (Twaron / Kevlar). In biochemistry peptides are synthesized in solid phase peptide synthesis. The Schotten-Baumann reaction describes the formation of amides from amines and acid chlorides.
- Cyclic amides are synthesized in the Beckmann rearrangement from oximes.
- Amides also form ketones in the Schmidt reaction
- Amides can be prepared from aryl alkyl ketones, sulfur and morpholine in the Willgerodt-Kindler reaction
- Other amide-forming reactions are the Passerini reaction and the Ugi reaction
- In the Bodroux reaction an amide RNHCOR' is synthesized from a carboxylic acid R-COOH and the adduct of a Grignard reagent with an aniline derivative ArNHR'
- In the Chapman rearrangement (first reported in 1925) an aryl imino ester is converted to a N,N-diaryl amide:
# Amide reactions
- Amide breakdown is possible via amide hydrolysis. Such hydrolysis can occur under basic or acidic conditions. Acidic conditions yield the carboxylic acid and the ammonium ion while basic hydrolysis yield the carboxylate ion and ammonia.
- In the Vilsmeier-Haack reaction an amide is converted into an imine.
- Hofmann rearrangement of primary amides to primary amines.
Owing to their resonance stabilization, amides are relatively unreactive under physiological conditions, even less than similar compounds such as esters. Nevertheless, amides can undergo chemical reactions, usually through an attack of an electronegative atom on the carbonyl carbon, breaking the carbonyl double bond and forming a tetrahedral intermediate. When the functional group attacking the amide is a thiol, hydroxyl or amine, the resulting molecule may be called a cyclol or, more specifically, a thiacyclol, an oxacyclol or an azacyclol, respectively.
The proton of an amide does not dissociate readily under normal conditions; its pKa is usually well above 15. However, under extremely acidic conditions, the carbonyl oxygen can become protonated with a pKa of roughly -1.
Amides will react with nitrous acid (HONO) forming the carboxylic acid and yielding nitrogen. Nitrous acid is formed by addition of a strong acid to a nitrate (III) salt in solution at temperatures of between 0 and 10 degrees.
Amides undergo Hofmann's degradation reaction in which an amide yields an amine with one less carbon atom upon reaction with bromine and sodium hydroxide. One should also note that reacting the amide with the strong reducing agent lithium tetrahidridoaluminate yields an amine with the same number of carbon atoms.
Amides are dehydrated with phosphorus (V) oxide forming the nitrile. Care should be taken when performing such a reaction since phosphorus (V) oxide smoulders when in contact with organic matter.
# Amide linkage (peptide bond)
An amide linkage is kinetically stable to hydrolysis. However, it can be hydrolysed in boiling alkali, as well as in strong acidic conditions. Amide linkages in a biochemical context are called peptide linkages. Amide linkages constitute a defining molecular feature of proteins, the secondary structure of which is due in part to the hydrogen bonding abilities of amides.
# Amide properties
Compared to amines, amides are very weak bases. While the conjugate acid of an amine has a pKa of about 9.5, the conjugate acid of an amide has a pKa around -0.5. Therefore amides don't have as clearly noticeable acid-base properties in water. This lack of basicity is explained by the electron-withdrawing nature of the carbonyl group where the lone pair of electrons on the nitrogen is delocalized by resonance, thus forming a partial double bond with the carbonyl carbon and putting a negative charge on the oxygen. On the other hand, amides are much stronger bases than carboxylic acids, esters, aldehydes, and ketones (conjugated acid pKa between -6 and -10). It is estimated in silico that acetamide is represented by resonance structure A for 62% and by B for 28% . Resonance is largely prevented in the very strained quinuclidone.
# Solubility
Amides contain carbonyl (C=O) and ether (N-C) dipoles arising from covalent bonding between electronegative oxygen and nitrogen atoms and electro-neutral carbon atoms. Primary and secondary amides also contain two- and one N-H dipoles, respectively. Because of the pi-bonding arrangement of the carbonyl and the greater electronegativity of oxygen, the carbonyl (C=O) is a stronger dipole than the N-C dipole. The presence of a C=O dipole and, to a lesser extent a N-C dipole, allows amides to act as H-bond acceptors. In primary and secondary amides, the presence of N-H dipoles allows amides to function as H-bond donors as well. Thus amides can participate in hydrogen bonding with water and other protic solvents; the oxygen and nitrogen atoms can accept hydrogen bonds from water and the N-H hydrogen atoms can donate H-bonds. As a result of interactions such as these, the water solubility of amides is greater than that of corresponding hydrocarbons
While hydrogen bonding may enhance the water solubility of amides relative to hydrocarbons (alkanes, alkenes, alkynes and aromatic compounds), amides typically are regarded as compounds with low water solubility. They are significantly less water soluble than comparable acids or alcohols due to:
1). their non-ionic character
2). the presence of nonpolar hydrocarbon functionality, and
3). the inability of tertiary amides to donate hydrogen bonds to water (they can only be H-bond acceptors).
Thus amides have water solubilities roughly comparable to esters. Typically amides are less soluble than comparable amines and carboxylic acids since these compounds can both donate and accept hydrogen bonds, and can ionize at appropriate pHs to further enhance solubility
# Derivatives
Sulfonamides are analogues of amides in which the atom double-bonded to oxygen is sulfur rather than carbon.
Cyclic amides are called lactams.
# Naming conventions
- Example: CH3CONH2 is named acetamide or ethanamide
- Other examples: propan-1-amide, N,N-dimethylpropanamide, acrylamide
- For more detail see IUPAC nomenclature of organic chemistry - Amines and Amides | Amide
In chemistry, an amide is one of two kinds of compounds:
- the organic functional group characterized by a carbonyl group (C=O) linked to a nitrogen atom (N), or a compound that contains this functional group (pictured to the right); or
- a particular kind of nitrogen anion.
Amides are the most stable of all the carbonyl functional groups.
Many chemists make a pronunciation distinction between the two, saying (Template:IPA2 for the carbonyl-nitrogen compound and ['æmɑɪd] for the anion. Others substitute one of these pronunciations with ['æmɪd], while still others pronounce both as ['æmɪd], making them homonyms.
In the first sense referred to above, an amide is an amine where one of the nitrogen substituents is an acyl group; it is generally represented by the formula: R1(CO)NR2R3 , where either or both R2 and R3 may be hydrogen. Specifically, an amide can also be regarded as a derivative of a carboxylic acid in which the hydroxyl group has been replaced by an amine or ammonia.
Compounds in which a hydrogen atom on nitrogen from ammonia or an amine is replaced by a metal cation are also known as amides or azanides.
The second sense of the word amide is the amide anion, which is a deprotonated form of ammonia (NH3) or an amine. It is generally represented by the formula: [R1NR2]-, and is an extremely strong base, due to the extreme weakness of ammonia and its analogues as Brønsted acids.
The remainder of this article is about the carbonyl-nitrogen sense of amide. For examples of the anionic amide, see the articles Sodium amide and Lithium diisopropylamide.
# Amide synthesis
- Amides are commonly formed from the reaction of a carboxylic acid with an amine. This is the reaction that forms peptide bonds between amino acids. These amides can participate in hydrogen bonding as hydrogen bond acceptors and donors, but do not ionize in aqueous solution, whereas their parent acids and amines are almost completely ionized in solution at neutral pH. Amide formation plays a role in the synthesis of some condensation polymers, such as nylon and Aramid (Twaron / Kevlar). In biochemistry peptides are synthesized in solid phase peptide synthesis. The Schotten-Baumann reaction describes the formation of amides from amines and acid chlorides.
- Cyclic amides are synthesized in the Beckmann rearrangement from oximes.
- Amides also form ketones in the Schmidt reaction
- Amides can be prepared from aryl alkyl ketones, sulfur and morpholine in the Willgerodt-Kindler reaction
- Other amide-forming reactions are the Passerini reaction and the Ugi reaction
- In the Bodroux reaction an amide RNHCOR' is synthesized from a carboxylic acid R-COOH and the adduct of a Grignard reagent with an aniline derivative ArNHR' [1] [2]
- In the Chapman rearrangement (first reported in 1925) an aryl imino ester is converted to a N,N-diaryl amide:
# Amide reactions
- Amide breakdown is possible via amide hydrolysis. Such hydrolysis can occur under basic or acidic conditions. Acidic conditions yield the carboxylic acid and the ammonium ion while basic hydrolysis yield the carboxylate ion and ammonia.
- In the Vilsmeier-Haack reaction an amide is converted into an imine.
- Hofmann rearrangement of primary amides to primary amines.
Owing to their resonance stabilization, amides are relatively unreactive under physiological conditions, even less than similar compounds such as esters. Nevertheless, amides can undergo chemical reactions, usually through an attack of an electronegative atom on the carbonyl carbon, breaking the carbonyl double bond and forming a tetrahedral intermediate. When the functional group attacking the amide is a thiol, hydroxyl or amine, the resulting molecule may be called a cyclol or, more specifically, a thiacyclol, an oxacyclol or an azacyclol, respectively.
The proton of an amide does not dissociate readily under normal conditions; its pKa is usually well above 15. However, under extremely acidic conditions, the carbonyl oxygen can become protonated with a pKa of roughly -1.
Amides will react with nitrous acid (HONO) forming the carboxylic acid and yielding nitrogen. Nitrous acid is formed by addition of a strong acid to a nitrate (III) salt in solution at temperatures of between 0 and 10 degrees.
Amides undergo Hofmann's degradation reaction in which an amide yields an amine with one less carbon atom upon reaction with bromine and sodium hydroxide. One should also note that reacting the amide with the strong reducing agent lithium tetrahidridoaluminate yields an amine with the same number of carbon atoms.
Amides are dehydrated with phosphorus (V) oxide forming the nitrile. Care should be taken when performing such a reaction since phosphorus (V) oxide smoulders when in contact with organic matter.
# Amide linkage (peptide bond)
An amide linkage is kinetically stable to hydrolysis. However, it can be hydrolysed in boiling alkali, as well as in strong acidic conditions. Amide linkages in a biochemical context are called peptide linkages. Amide linkages constitute a defining molecular feature of proteins, the secondary structure of which is due in part to the hydrogen bonding abilities of amides.
# Amide properties
Compared to amines, amides are very weak bases. While the conjugate acid of an amine has a pKa of about 9.5, the conjugate acid of an amide has a pKa around -0.5. Therefore amides don't have as clearly noticeable acid-base properties in water. This lack of basicity is explained by the electron-withdrawing nature of the carbonyl group where the lone pair of electrons on the nitrogen is delocalized by resonance, thus forming a partial double bond with the carbonyl carbon and putting a negative charge on the oxygen. On the other hand, amides are much stronger bases than carboxylic acids, esters, aldehydes, and ketones (conjugated acid pKa between -6 and -10). It is estimated in silico that acetamide is represented by resonance structure A for 62% and by B for 28% [4]. Resonance is largely prevented in the very strained quinuclidone.
# Solubility
Amides contain carbonyl (C=O) and ether (N-C) dipoles arising from covalent bonding between electronegative oxygen and nitrogen atoms and electro-neutral carbon atoms. Primary and secondary amides also contain two- and one N-H dipoles, respectively. Because of the pi-bonding arrangement of the carbonyl and the greater electronegativity of oxygen, the carbonyl (C=O) is a stronger dipole than the N-C dipole. The presence of a C=O dipole and, to a lesser extent a N-C dipole, allows amides to act as H-bond acceptors. In primary and secondary amides, the presence of N-H dipoles allows amides to function as H-bond donors as well. Thus amides can participate in hydrogen bonding with water and other protic solvents; the oxygen and nitrogen atoms can accept hydrogen bonds from water and the N-H hydrogen atoms can donate H-bonds. As a result of interactions such as these, the water solubility of amides is greater than that of corresponding hydrocarbons
While hydrogen bonding may enhance the water solubility of amides relative to hydrocarbons (alkanes, alkenes, alkynes and aromatic compounds), amides typically are regarded as compounds with low water solubility. They are significantly less water soluble than comparable acids or alcohols due to:
1). their non-ionic character
2). the presence of nonpolar hydrocarbon functionality, and
3). the inability of tertiary amides to donate hydrogen bonds to water (they can only be H-bond acceptors).
Thus amides have water solubilities roughly comparable to esters. Typically amides are less soluble than comparable amines and carboxylic acids since these compounds can both donate and accept hydrogen bonds, and can ionize at appropriate pHs to further enhance solubility
# Derivatives
Sulfonamides are analogues of amides in which the atom double-bonded to oxygen is sulfur rather than carbon.
Cyclic amides are called lactams.
# Naming conventions
- Example: CH3CONH2 is named acetamide or ethanamide
- Other examples: propan-1-amide, N,N-dimethylpropanamide, acrylamide
- For more detail see IUPAC nomenclature of organic chemistry - Amines and Amides | https://www.wikidoc.org/index.php/Amidation | |
fe7016602a17c651c92ef924d49f6e590ebd1743 | wikidoc | Anise | Anise
# Overview
Anise or Aniseed, less commonly anís (stressed on the second syllable) (Pimpinella anisum), is a flowering plant in the family Apiaceae, native to the eastern Mediterranean region and southwest Asia. It is a herbaceous annual plant growing to 1m tall. The leaves at the base of the plant are simple, 2-5 cm long and shallowly lobed, while leaves higher on the stems are feathery pinnate, divided into numerous leaflets. The flowers are white, 3 mm diameter, produced in dense umbels. The fruit is an oblong dry schizocarp, 3-5 mm long.
Pimpinella species are used as food plants by the larvae of some Lepidoptera species, including the lime-speck pug and wormwood pug.
# Uses
## Culinary
- Sweet and very aromatic. Anise contains liquorice-like components.
- Aniseed is used to make the British confectionery Aniseed balls and the old fashioned New Zealand confectionery, Aniseed wheels.
- Aniseed is also used to make the Mexican drink atole called champurrado(similar to hot chocolate).
- Anise oil is used to make Italian cookies called pizzelles, and used in the frosting of yellow Italian cake-like cookies called "Drops" or "Anise Drops."
- Anise flavouring is used in the Norwegian candy pills "Knott", produced by Nidar.
- Anise toast is a dry bread popular in Italy.
- Anise (Saunf,Badi-Sheb) is used in India as a digestive after meals.
## Medicinal uses
- Anise leaves are used to treat digestive problems, to relieve toothache, and its essential oil is used to treat lice and scabies.
- In aromatherapy, aniseed essential oil is used to treat colds and flu. It is being researched for the treatment of bird flu as well.
- In India, aniseed (Saunf in Hindi) is also used as mouth freshener. It is also used for flavouring some foods.
- According to Pliny the Elder, anise was used as a cure for sleeplessness, chewed with alexanders and a little honey in the morning to freshen the breath, and when mixed with wine as a remedy for scorpion stings (N.H. 20.72).
- In the Middle East, aniseed is used in producing alcoholic beverages, such as Arak (Morocco) and Ouzo (Greece).
- In Thailand it is used to flavor tea.
## Other uses
Anise can be made into a liquid scent and is used for both hunting and fishing. Anise smells similar to liquorice and is put on fishing lures to attract fish. Anethole, the principal component of anise oil is a precursor that can eventually produce 2,5-dimethoxybenzaldehyde which is used in the clandestine synthesis of psychedelic drugs such as 2C-B, 2C-I and DOB.
Anise is also the main flavor of Absinthe as well as being used as a flavoring for pastis, ouzo, pernod, sambuca, Raki, Becherovka, anice tutone, Chartreuse and other liqueurs. Anise has a particular effect on some dogs that parallels the effect of catnip on house cats. Some cats as well seem attracted to anise. Anise is perfectly safe for cats and dogs alike to ingest. However, like anything, not in excess. | Anise
# Overview
Anise or Aniseed, less commonly anís (stressed on the second syllable) (Pimpinella anisum), is a flowering plant in the family Apiaceae, native to the eastern Mediterranean region and southwest Asia. It is a herbaceous annual plant growing to 1m tall. The leaves at the base of the plant are simple, 2-5 cm long and shallowly lobed, while leaves higher on the stems are feathery pinnate, divided into numerous leaflets. The flowers are white, 3 mm diameter, produced in dense umbels. The fruit is an oblong dry schizocarp, 3-5 mm long.
Pimpinella species are used as food plants by the larvae of some Lepidoptera species, including the lime-speck pug and wormwood pug.
# Uses
## Culinary
- Sweet and very aromatic. Anise contains liquorice-like components. [1]
- Aniseed is used to make the British confectionery Aniseed balls and the old fashioned New Zealand confectionery, Aniseed wheels.
- Aniseed is also used to make the Mexican drink atole called champurrado(similar to hot chocolate).
- Anise oil is used to make Italian cookies called pizzelles, and used in the frosting of yellow Italian cake-like cookies called "Drops" or "Anise Drops."
- Anise flavouring is used in the Norwegian candy pills "Knott", produced by Nidar.
- Anise toast is a dry bread popular in Italy.
- Anise (Saunf,Badi-Sheb) is used in India as a digestive after meals.
## Medicinal uses
- Anise leaves are used to treat digestive problems, to relieve toothache, and its essential oil is used to treat lice and scabies.
- In aromatherapy, aniseed essential oil is used to treat colds and flu. It is being researched for the treatment of bird flu as well.[2]
- In India, aniseed (Saunf in Hindi) is also used as mouth freshener. It is also used for flavouring some foods.
- According to Pliny the Elder, anise was used as a cure for sleeplessness, chewed with alexanders and a little honey in the morning to freshen the breath, and when mixed with wine as a remedy for scorpion stings (N.H. 20.72).
- In the Middle East, aniseed is used in producing alcoholic beverages, such as Arak (Morocco) and Ouzo (Greece).
- In Thailand it is used to flavor tea.
## Other uses
Anise can be made into a liquid scent and is used for both hunting and fishing. Anise smells similar to liquorice and is put on fishing lures to attract fish. Anethole, the principal component of anise oil is a precursor that can eventually produce 2,5-dimethoxybenzaldehyde which is used in the clandestine synthesis of psychedelic drugs such as 2C-B, 2C-I and DOB.[3]
Anise is also the main flavor of Absinthe as well as being used as a flavoring for pastis, ouzo, pernod, sambuca, Raki, Becherovka, anice tutone, Chartreuse and other liqueurs. Anise has a particular effect on some dogs that parallels the effect of catnip on house cats. Some cats as well seem attracted to anise. Anise is perfectly safe for cats and dogs alike to ingest. However, like anything, not in excess. | https://www.wikidoc.org/index.php/Anise | |
e52504dace8ecabe4af584d9116dd2dd8ebad074 | wikidoc | Ankle | Ankle
In human anatomy, the ankle joint is formed where the foot and the leg meet. The ankle, or talocrural joint, is a synovial hinge joint that connects the distal ends of the tibia and fibula in the lower limb with the proximal end of the talus bone in the foot. The articulation between the tibia and the talus bears more weight than between the smaller fibula and the talus.
The term "ankle" is used to describe structures in the region of the ankle joint proper.
# Movement
The ankle joint is responsible for dorsiflexion (moving the toes up as when standing only on the heels) and plantar flexion of the foot (moving the toes down, as when standing on the toes), and allows for the greatest movement of all the joints in the foot. The ankle does not allow rotation.
In plantar flexion, the anterior ligaments of the joint become longer while the posterior ligaments become shorter. The reverse is true for dorsiflexion.
# Articulation
The lateral malleolus of the fibula and the medial malleolus of the tibia along with the inferior surface of the distal tibia articulate with three facets of the talus. These surfaces are covered by cartilage.
The anterior talus is wider than the posterior talus. When the foot is dorsiflexed , the wider part of the superior talus moves into the articulating surfaces of the tibia and fibula, creating a more stable joint than when the foot is plantar flexed.
# Ligaments
The ankle joint is bound by the strong deltoid ligament and three lateral ligaments: the anterior talofibular ligament, the posterior talofibular ligament, and the calcaneofibular ligament.
- The deltoid ligament supports the medial side of the joint, and is attached at the medial malleolus of the tibia and connect in four places to the sustentaculum tali of the calcaneus, calcaneonavicular ligament, the navicular tuberosity, and to the medial surface of the talus.
- The anterior and posterior talofibular ligaments support the lateral side of the joint from the lateral malleolus of the fibula to the dorsal and ventral ends of the talus.
- The calcaneofibular ligament is attached at the lateral malleolus and to the lateral surface of the calcaneus.
The joint is most stable in dorsiflexion and a sprained ankle is more likely to occur when the foot is plantar flexed. This type of injury more frequently occurs at the anterior talofibular ligament.
# Name derivation
The word ankle or ancle is common, in various forms, to Germanic languages, probably connected in origin with the Latin "angulus", or Greek "αγκυλος", meaning bent.
# Related terms
A common variant of the word "ankle" is "cankle", which is commonly used derogatorily to describe the ankles of obese individuals where the ankle and calf may be indistinguishable. This insult can be taken further (often jokingly) using the term "thankle", which implies a person's thighs and ankles are indistinguishable.
# Fractures
Most traumatic incidents involving the ankle result in ankle sprains. Symptoms of an ankle fracture can be similar than for sprains (pain, hematoma) or there may be an abnormal position, abnormal movement or lack of movement (if there is an accompanying dislocation), or the patient may have heard a crack.
On clinical examination, it is important to evaluate the exact location of the pain, the range of motion and the condition of the nerves and vessels. It is important to palpate the calf bone (fibula) because there may be an associated fracture, and to palpate the sole of the foot to look for a Jones fracture.
Evaluation of ankle injuries for fracture is done with the Ottawa ankle rules, a set of rules that were developed to minimize unnecessary X-rays. On X-rays, there can be a fracture of the medial malleolus, the lateral malleolus, or the anterior or posterior margin. If both malleoli are broken, this is called a bimalleolar fracture (some of them are called Pott's fractures). If three of these are broken at the same time, this is called a trimalleolar fracture (although there are only two malleoli). Ankle fractures are classified according to Weber, depending on their position relative to the anterior ligament of the lateral malleolus (type A = below the ligament, type B = at its level, type C = above the ligament). A special form of type C fracture is the Maisonneuve fracture, which involves a spiral fracture of the fibula with a tear of the distal tibiofibular syndesmosis and the interosseous membrane.
Only type A fractures of the lateral malleolus can be treated like sprains; all other types require surgery (most often an open reduction and internal fixation). A cast may be required to immobilize the ankle following surgery. Trimalleolar fractures or those with dislocation have a high risk of developing arthrosis.
# Additional images
- The bones in the foot.
The bones in the foot.
- Ligaments of the medial aspect of the foot.
- The ligaments of the foot from the lateral aspect.
- Capsule of left talocrura articulation (distended). Lateral aspect.
- Oblique section of left intertarsal and tarsometatarsal articulations, showing the synovial cavities. | Ankle
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Template:Infobox Anatomy
In human anatomy, the ankle joint is formed where the foot and the leg meet. The ankle, or talocrural joint, is a synovial hinge joint that connects the distal ends of the tibia and fibula in the lower limb with the proximal end of the talus bone in the foot.[1] The articulation between the tibia and the talus bears more weight than between the smaller fibula and the talus.
The term "ankle" is used to describe structures in the region of the ankle joint proper.[2]
# Movement
The ankle joint is responsible for dorsiflexion (moving the toes up as when standing only on the heels) and plantar flexion of the foot (moving the toes down, as when standing on the toes), and allows for the greatest movement of all the joints in the foot. The ankle does not allow rotation.
In plantar flexion, the anterior ligaments of the joint become longer while the posterior ligaments become shorter. The reverse is true for dorsiflexion.
# Articulation
The lateral malleolus of the fibula and the medial malleolus of the tibia along with the inferior surface of the distal tibia articulate with three facets of the talus. These surfaces are covered by cartilage.
The anterior talus is wider than the posterior talus. When the foot is dorsiflexed , the wider part of the superior talus moves into the articulating surfaces of the tibia and fibula, creating a more stable joint than when the foot is plantar flexed.
# Ligaments
The ankle joint is bound by the strong deltoid ligament and three lateral ligaments: the anterior talofibular ligament, the posterior talofibular ligament, and the calcaneofibular ligament.
- The deltoid ligament supports the medial side of the joint, and is attached at the medial malleolus of the tibia and connect in four places to the sustentaculum tali of the calcaneus, calcaneonavicular ligament, the navicular tuberosity, and to the medial surface of the talus.
- The anterior and posterior talofibular ligaments support the lateral side of the joint from the lateral malleolus of the fibula to the dorsal and ventral ends of the talus.
- The calcaneofibular ligament is attached at the lateral malleolus and to the lateral surface of the calcaneus.
The joint is most stable in dorsiflexion and a sprained ankle is more likely to occur when the foot is plantar flexed. This type of injury more frequently occurs at the anterior talofibular ligament.
# Name derivation
The word ankle or ancle is common, in various forms, to Germanic languages, probably connected in origin with the Latin "angulus", or Greek "αγκυλος", meaning bent.
# Related terms
A common variant of the word "ankle" is "cankle", which is commonly used derogatorily to describe the ankles of obese individuals where the ankle and calf may be indistinguishable. This insult can be taken further (often jokingly) using the term "thankle", which implies a person's thighs and ankles are indistinguishable.
# Fractures
Most traumatic incidents involving the ankle result in ankle sprains. Symptoms of an ankle fracture can be similar than for sprains (pain, hematoma) or there may be an abnormal position, abnormal movement or lack of movement (if there is an accompanying dislocation), or the patient may have heard a crack.
On clinical examination, it is important to evaluate the exact location of the pain, the range of motion and the condition of the nerves and vessels. It is important to palpate the calf bone (fibula) because there may be an associated fracture, and to palpate the sole of the foot to look for a Jones fracture.
Evaluation of ankle injuries for fracture is done with the Ottawa ankle rules, a set of rules that were developed to minimize unnecessary X-rays. On X-rays, there can be a fracture of the medial malleolus, the lateral malleolus, or the anterior or posterior margin. If both malleoli are broken, this is called a bimalleolar fracture (some of them are called Pott's fractures). If three of these are broken at the same time, this is called a trimalleolar fracture (although there are only two malleoli). Ankle fractures are classified according to Weber, depending on their position relative to the anterior ligament of the lateral malleolus (type A = below the ligament, type B = at its level, type C = above the ligament). A special form of type C fracture is the Maisonneuve fracture, which involves a spiral fracture of the fibula with a tear of the distal tibiofibular syndesmosis and the interosseous membrane.
Only type A fractures of the lateral malleolus can be treated like sprains; all other types require surgery (most often an open reduction and internal fixation). A cast may be required to immobilize the ankle following surgery. Trimalleolar fractures or those with dislocation have a high risk of developing arthrosis.
# Additional images
- The bones in the foot.
The bones in the foot.
- Ligaments of the medial aspect of the foot.
- The ligaments of the foot from the lateral aspect.
- Capsule of left talocrura articulation (distended). Lateral aspect.
- Oblique section of left intertarsal and tarsometatarsal articulations, showing the synovial cavities. | https://www.wikidoc.org/index.php/Ankle | |
581b50dca37950f341c3b575e84f8dac6474e3a8 | wikidoc | Anode | Anode
An anode is an electrode through which (positive) electric current flows into a polarized electrical device. Mnemonic: ACID (Anode Current Into Device). Electrons flow in the opposite direction to the positive electric current.
To dispel a common misconception, often incorrectly inferred from the correct fact that in all electrochemical devices negatively charged anions move towards the anode and/or positively charged cations move away from it, anode polarity is not always positive but depends on the device type, and sometimes even in which mode it operates, as determined by the above current direction-based universal definition. Examples:
- In a discharging battery or galvanic cell (drawing) the anode is the negative terminal, where conventional current flows in, and electrons out. Since this inwards current is carried externally by electrons moving outwards, the negative charge moving one way amounts to positive current flowing the other way. At the anode, the current is continued internally by positive ions (cations) moving into the electrolyte from the anode, i.e., away (surprisingly) from the more negative electrode and towards the more positive one (chemical energy is responsible for this "uphill" motion). If the anode is composed of a metal, electrons which it gives up to the external circuit must be accompanied by metal atoms missing those electrions (cations) moving away from the electrode and into the electrolyte.
- In a recharging battery, or an electrolytic cell, the anode is the positive terminal, which receives current from an external generator.
- In a diode, it is the positive terminal at the tail of the arrow symbol, where current flows into the device. Note electrode naming for diodes is always based on the direction of the forward current (that of the arrow, in which the current flows "most easily"), even for types such as zener diodes or solar cells where the current of interest is the reverse current.
- In a cathode ray tube, it is the positive terminal where electrons flow out, i.e., where current flows in.
An electrode through which current flows the other way (out) is a cathode.
# Etymology
The word was coined in 1834 from the Greek ἄνοδος (anodos), 'way up', by William Whewell, who had been consulted by Michael Faraday over some new names needed to complete a paper on the recently discovered process of electrolysis. In that paper Faraday explained that when an electrolytic cell is oriented so that electric current traverses the "decomposing body" (electrolyte) in a direction "from East to West, or, which will strengthen this help to the memory, that in which the sun appears to move", the anode is where the current enters the electrolyte, on the East side: "ano upwards, odos a way ; the way which the sun rises" (, reprinted in ).
The use of 'East' to mean the 'in' direction (actually 'in' → 'East' → 'sunrise' → 'up') may appear unnecessarily contrived. Previously, as related in the first reference cited above, Faraday had used the more straightforward term "eisode" (the doorway where the current enters). His motivation for changing it to something meaning 'the East electrode' (other candidates had been "eastode", "oriode" and "anatolode") was to make it immune to a possible later change in the direction convention for current, whose exact nature was not known at the time. The reference he used to this effect was the Earth's magnetic field direction, which at that time was believed to be invariant. He fundamentally defined his arbitrary orientation for the cell as being that in which the internal current would run parallel to and in the same direction as a hypothetical magnetizing current loop around the local line of latitude which would induce a magnetic dipole field oriented like the Earth's. This made the internal current East to West as previously mentioned, but in the event of a later convention change it would have become West to East, so that the East electrode would not have been the 'way in' any more. Therefore "eisode" would have become inappropriate, whereas "anode" meaning 'East electrode' would have remained correct with respect to the unchanged direction of the actual phenomenon underlying the current, then unknown but, he thought, unambiguously defined by the magnetic reference. In retrospect the name change was unfortunate, not only because the Greek roots alone do not reveal the anode's function any more, but more importantly because, as we now know, the Earth's magnetic field direction on which the "anode" term is based is subject to reversals whereas the current direction convention on which the "eisode" term was based has no reason to change in the future.
Since the later discovery of the electron, an easier to remember, and more durably correct technically although historically false, etymology has been suggested: anode, from the Greek anodos, 'way up', 'the way (up) out of the cell (or other device) for electrons'.
# Flow of electrons
The flow of electrons is always from anode to cathode outside of the cell or device, regardless of the cell or device type and operating mode, with the exception of diodes, where electrode naming always assumes current flows in the forward direction (that of the arrow symbol), i.e., electrons flow in the opposite direction, even when the diode reverse-conducts either by accident (breakdown of a normal diode) or by design (breakdown of a Zener diode, photo-current of a photodiode or solar cell).
# Electrolytic anode
In electrochemistry, the anode is where oxidation occurs, and is the positive polarity contact in an electrolytic cell. At the anode, anions (negative ions) are forced by the electrical potential to react chemically and give off electrons (oxidation) which then flow up and into the driving circuit.
# Battery or galvanic cell anode
In a battery or galvanic cell, the anode is the negative electrode from which electrons flow out towards the external part of the circuit. Internally the positively charged cations are flowing away from the anode (even though it is negative and therefore would be expected to attract them, this is due to electrode potential relative to the electrolyte solution being different for the anode and cathode metal/electrolyte systems); but, external to the cell in the circuit, electrons are being pushed out through the negative contact and thus through the circuit by the voltage potential as would be expected. Note: in a galvanic cell, contrary to what occurs in an electrolytic cell, no anions flow to the anode, the internal current being entirely accounted for by the cations flowing away from it (cf drawing).
In the United States, many battery manufacturers regard the positive electrode as the anode, particularly in their technical literature. Though technically incorrect, it does resolve the problem of which electrode is the anode in a secondary (or rechargeable) cell. Using the traditional definition, the anode switches ends between charge and discharge cycles.
# Vacuum tube anode
In electronic vacuum devices such as a cathode ray tube, the anode is the positively charged electron collector. In a tube, the anode is a charged positive plate that collects the electrons emitted by the cathode through electric attraction.
# Diode anode
In a semiconductor diode, the anode is the P-doped layer which initially supplies holes to the junction. In the junction region, the holes supplied by the anode combine with electrons supplied from the N-doped region, creating a depleted zone. As the P-doped layer supplies holes to the depleted region, negative dope ions are left behind in the P-doped layer ('P' for positive charge-carrier ions). This creates a base negative charge on the anode. When a positive voltage is applied to anode of the diode from the circuit, more holes are able to be transferred to the depleted region, and this causes the diode to become conductive, allowing current to flow through the circuit. The terms anode and cathode should not be applied to a zener diode, since it allows flow in either direction, depending on the polarity of the applied potential (i.e. voltage).
# Sacrificial anode
In cathodic protection, a metal anode that is more reactive to the corrosive environment of the system to be protected is electrically linked to the protected system, and partially corrodes or dissolves, which protects the metal of the system it is connected to. As an example, an iron or steel ship's hull may be protected by a zinc sacrificial anode, which will dissolve into the seawater and prevent the hull from being corroded. Sacrificial anodes are particularly needed for systems where a static charge is generated by the action of flowing liquids, such as pipelines and watercraft.
At least one anode is found in tank-type hot water heaters. The anode should be removed and checked after 5 years(sooner if there is a sodium based water softner inline), and replaced if 6 inches (15 cm) or more of bare wire is showing. This will greatly extend the life of the tank.
Water heater anode information
# Related antonym
The opposite of an anode is a cathode. When the current through the device is reversed, the electrodes switch functions, so anode becomes cathode, while cathode becomes anode, as long as the reversed current is applied, with the exception of diodes where electrode naming is always based on the forward current direction. | Anode
An anode is an electrode through which (positive) electric current flows into a polarized electrical device. Mnemonic: ACID (Anode Current Into Device). Electrons flow in the opposite direction to the positive electric current.
To dispel a common misconception, often incorrectly inferred from the correct fact that in all electrochemical devices negatively charged anions move towards the anode and/or positively charged cations move away from it, anode polarity is not always positive but depends on the device type, and sometimes even in which mode it operates, as determined by the above current direction-based universal definition. Examples:
- In a discharging battery or galvanic cell (drawing) the anode is the negative terminal, where conventional current flows in, and electrons out. Since this inwards current is carried externally by electrons moving outwards, the negative charge moving one way amounts to positive current flowing the other way. At the anode, the current is continued internally by positive ions (cations) moving into the electrolyte from the anode, i.e., away (surprisingly) from the more negative electrode and towards the more positive one (chemical energy is responsible for this "uphill" motion). If the anode is composed of a metal, electrons which it gives up to the external circuit must be accompanied by metal atoms missing those electrions (cations) moving away from the electrode and into the electrolyte.
- In a recharging battery, or an electrolytic cell, the anode is the positive terminal, which receives current from an external generator.
- In a diode, it is the positive terminal at the tail of the arrow symbol, where current flows into the device. Note electrode naming for diodes is always based on the direction of the forward current (that of the arrow, in which the current flows "most easily"), even for types such as zener diodes or solar cells where the current of interest is the reverse current.
- In a cathode ray tube, it is the positive terminal where electrons flow out, i.e., where current flows in.
An electrode through which current flows the other way (out) is a cathode.
# Etymology
The word was coined in 1834 from the Greek ἄνοδος (anodos), 'way up', by William Whewell, who had been consulted[1] by Michael Faraday over some new names needed to complete a paper on the recently discovered process of electrolysis. In that paper Faraday explained that when an electrolytic cell is oriented so that electric current traverses the "decomposing body" (electrolyte) in a direction "from East to West, or, which will strengthen this help to the memory, that in which the sun appears to move", the anode is where the current enters the electrolyte, on the East side: "ano upwards, odos a way ; the way which the sun rises" ([2], reprinted in [3]).
The use of 'East' to mean the 'in' direction (actually 'in' → 'East' → 'sunrise' → 'up') may appear unnecessarily contrived. Previously, as related in the first reference cited above, Faraday had used the more straightforward term "eisode" (the doorway where the current enters). His motivation for changing it to something meaning 'the East electrode' (other candidates had been "eastode", "oriode" and "anatolode") was to make it immune to a possible later change in the direction convention for current, whose exact nature was not known at the time. The reference he used to this effect was the Earth's magnetic field direction, which at that time was believed to be invariant. He fundamentally defined his arbitrary orientation for the cell as being that in which the internal current would run parallel to and in the same direction as a hypothetical magnetizing current loop around the local line of latitude which would induce a magnetic dipole field oriented like the Earth's. This made the internal current East to West as previously mentioned, but in the event of a later convention change it would have become West to East, so that the East electrode would not have been the 'way in' any more. Therefore "eisode" would have become inappropriate, whereas "anode" meaning 'East electrode' would have remained correct with respect to the unchanged direction of the actual phenomenon underlying the current, then unknown but, he thought, unambiguously defined by the magnetic reference. In retrospect the name change was unfortunate, not only because the Greek roots alone do not reveal the anode's function any more, but more importantly because, as we now know, the Earth's magnetic field direction on which the "anode" term is based is subject to reversals whereas the current direction convention on which the "eisode" term was based has no reason to change in the future.
Since the later discovery of the electron, an easier to remember, and more durably correct technically although historically false, etymology has been suggested: anode, from the Greek anodos, 'way up', 'the way (up) out of the cell (or other device) for electrons'.
# Flow of electrons
The flow of electrons is always from anode to cathode outside of the cell or device, regardless of the cell or device type and operating mode, with the exception of diodes, where electrode naming always assumes current flows in the forward direction (that of the arrow symbol), i.e., electrons flow in the opposite direction, even when the diode reverse-conducts either by accident (breakdown of a normal diode) or by design (breakdown of a Zener diode, photo-current of a photodiode or solar cell).
# Electrolytic anode
In electrochemistry, the anode is where oxidation occurs, and is the positive polarity contact in an electrolytic cell. At the anode, anions (negative ions) are forced by the electrical potential to react chemically and give off electrons (oxidation) which then flow up and into the driving circuit.
# Battery or galvanic cell anode
In a battery or galvanic cell, the anode is the negative electrode from which electrons flow out towards the external part of the circuit. Internally the positively charged cations are flowing away from the anode (even though it is negative and therefore would be expected to attract them, this is due to electrode potential relative to the electrolyte solution being different for the anode and cathode metal/electrolyte systems); but, external to the cell in the circuit, electrons are being pushed out through the negative contact and thus through the circuit by the voltage potential as would be expected. Note: in a galvanic cell, contrary to what occurs in an electrolytic cell, no anions flow to the anode, the internal current being entirely accounted for by the cations flowing away from it (cf drawing).
In the United States, many battery manufacturers regard the positive electrode as the anode, particularly in their technical literature. Though technically incorrect, it does resolve the problem of which electrode is the anode in a secondary (or rechargeable) cell. Using the traditional definition, the anode switches ends between charge and discharge cycles.
# Vacuum tube anode
In electronic vacuum devices such as a cathode ray tube, the anode is the positively charged electron collector. In a tube, the anode is a charged positive plate that collects the electrons emitted by the cathode through electric attraction.
# Diode anode
In a semiconductor diode, the anode is the P-doped layer which initially supplies holes to the junction. In the junction region, the holes supplied by the anode combine with electrons supplied from the N-doped region, creating a depleted zone. As the P-doped layer supplies holes to the depleted region, negative dope ions are left behind in the P-doped layer ('P' for positive charge-carrier ions). This creates a base negative charge on the anode. When a positive voltage is applied to anode of the diode from the circuit, more holes are able to be transferred to the depleted region, and this causes the diode to become conductive, allowing current to flow through the circuit. The terms anode and cathode should not be applied to a zener diode, since it allows flow in either direction, depending on the polarity of the applied potential (i.e. voltage).
# Sacrificial anode
In cathodic protection, a metal anode that is more reactive to the corrosive environment of the system to be protected is electrically linked to the protected system, and partially corrodes or dissolves, which protects the metal of the system it is connected to. As an example, an iron or steel ship's hull may be protected by a zinc sacrificial anode, which will dissolve into the seawater and prevent the hull from being corroded. Sacrificial anodes are particularly needed for systems where a static charge is generated by the action of flowing liquids, such as pipelines and watercraft.
At least one anode is found in tank-type hot water heaters. The anode should be removed and checked after 5 years(sooner if there is a sodium based water softner inline), and replaced if 6 inches (15 cm) or more of bare wire is showing. This will greatly extend the life of the tank.
Water heater anode information
# Related antonym
The opposite of an anode is a cathode. When the current through the device is reversed, the electrodes switch functions, so anode becomes cathode, while cathode becomes anode, as long as the reversed current is applied, with the exception of diodes where electrode naming is always based on the forward current direction. | https://www.wikidoc.org/index.php/Anode | |
e603194e1b841b50a51454e6b31805c6481f9810 | wikidoc | Apiol | Apiol
Apiol is an organic chemical compound, also known as parsley apiol, apiole or parsley camphor. It is found in parsley seeds and the essential oil of parsley. Heinrich Christoph Link, an apothecary in Leipzig, discovered the substance in 1715 as greenish crystals reduced by steam from oil of parsley. In 1855 Joret and Homolle discovered that apiol was an effective treatment of amenorrea or lack of menstruation.
In medicine it has been used, as essential oil or in purified form, for the treatment of menstruation disorders. It is an irritant and in high doses it is toxic and can cause liver and kidney damage.
Hippocrates wrote about parsley as a herb to cause an abortion. This effect was caused by the apiol.
Apiol was used by women in the Middle Ages to terminate pregnancies. Its use was widespread in the USA, often as ergoapiol or apergol, until a highly toxic adulterated product containing apiol and tri-orthocresyl phosphate (also famous as the adulterant added to Jamaican ginger) was introduced on the American market.
The toxic effects of pure crystalline apiol are disputed. It causes a "relatively safe abortion" in pregnant women if taken in small quantities. It also restores the cycle of menstruation. A larger dose does not cause an abortion, it causes nausea and damages the liver and kidneys.
Now that other methods of abortion are available apiol is almost forgotten in the West, but it is still produced and is used in the Middle East.
The name apiol is also used for other closely related compounds, found in dill (dillapiole, 1-allyl-2,3-dimethoxy-4,5-methylenedioxybenzene) and in fennel roots. | Apiol
Apiol is an organic chemical compound, also known as parsley apiol, apiole or parsley camphor. It is found in parsley seeds and the essential oil of parsley. Heinrich Christoph Link, an apothecary in Leipzig, discovered the substance in 1715 as greenish crystals reduced by steam from oil of parsley. In 1855 Joret and Homolle discovered that apiol was an effective treatment of amenorrea or lack of menstruation.
In medicine it has been used, as essential oil or in purified form, for the treatment of menstruation disorders. It is an irritant and in high doses it is toxic and can cause liver and kidney damage.
Hippocrates wrote about parsley as a herb to cause an abortion. This effect was caused by the apiol.
Apiol was used by women in the Middle Ages to terminate pregnancies.[citation needed] Its use was widespread in the USA, often as ergoapiol or apergol, until a highly toxic adulterated product containing apiol and tri-orthocresyl phosphate (also famous as the adulterant added to Jamaican ginger) was introduced on the American market.
The toxic effects of pure crystalline apiol are disputed. It causes a "relatively safe abortion" in pregnant women if taken in small quantities. It also restores the cycle of menstruation. A larger dose does not cause an abortion, it causes nausea and damages the liver and kidneys.[citation needed]
Now that other methods of abortion are available apiol is almost forgotten in the West, but it is still produced and is used in the Middle East.[citation needed]
The name apiol is also used for other closely related compounds, found in dill (dillapiole, 1-allyl-2,3-dimethoxy-4,5-methylenedioxybenzene) and in fennel roots.
# External links
- The British Pharmaceutical Codex 1911: Apiol
- Apiol chemical information from chemindustry.com
- NIH ChemIDplus: Apiole)
- Essential oil from fennel plants--studies on the composition | https://www.wikidoc.org/index.php/Apiol | |
ac8bba2a523e072f736315d850eb3c265475d0a5 | wikidoc | Argon | Argon
# Overview
Argon (Template:PronEng) is a chemical element designated by the symbol Ar. Argon has atomic number 18 and is the third element in group 18 of the periodic table (noble gases). Argon is present in the Earth's atmosphere at slightly less than 1%, making it the most common noble gas on Earth. Its full outer shell makes argon stable and resistant to bonding with other elements. Its triple point temperature of 83.8058 K is a defining fixed point in the International Temperature Scale of 1990.
# Characteristics
Argon has approximately the same solubility in water as oxygen gas and is 2.5 times more soluble in water than nitrogen gas. This highly stable chemical element is colorless, odorless, tasteless and nontoxic in both its liquid and gaseous forms. Argon is inert under most conditions and forms no confirmed stable compounds at room temperature.
Although argon is a noble gas, it has been found to have the capability of forming some compounds. For example, the creation of argon hydrofluoride (HArF), a metastable compound of argon with fluorine and hydrogen, has been reported by researchers at the University of Helsinki in 2000. Although the neutral ground-state chemical compounds of argon are presently limited to HArF, argon can form clathrates with water when atoms of it are trapped in a lattice of the water molecules. Also argon-containing ions e.g. ArH+ and excited state complexes e.g. ArF are well known. Theoretical calculations on computers have shown several argon compounds that should be stable but for which no synthesis routes are currently known.
# History
Argon (Greek αργόν meaning "the lazy one," in reference to its chemical inactivity) was suspected to be present in air by Henry Cavendish in 1785 but was not discovered until 1894 by Lord Rayleigh and Sir William Ramsay in an experiment in which they removed all of the oxygen and nitrogen from a sample of air. Argon was also encountered in 1882 through independent research of H.F. Newall and W.N. Hartley. Each observed new lines in the color spectrum of air but were unable to identify the element responsible for the lines. Argon became the first member of the noble gases to be discovered. The symbol for argon is now Ar, but up until 1957 it was A.
# Applications
There are several different reasons why argon is used in particular applications:
- An inert gas is needed. In particular, argon is the cheapest alternative when diatomic nitrogen is not sufficiently inert.
- Low thermal conductivity is required.
- The electronic properties (ionization and/or the emission spectrum) are necessary.
Other noble gases would probably work as well in most of these applications, but argon is by far the cheapest. Argon is inexpensive since it is a byproduct of the production of liquid oxygen and liquid nitrogen, both of which are used on a large industrial scale. The other noble gases (except helium) are produced this way as well, but argon is the most plentiful since it has the highest concentration in the atmosphere.
The bulk of argon applications arise simply because it is inert and relatively cheap. Argon is used:
- As a fill gas in incandescent lighting, because argon will not react with the filament of light bulbs even at high temperatures.
- As an inert gas shield in many forms of welding, including metal inert gas welding and tungsten inert gas welding.
- For extinguishing fires where damage to equipment is to be avoided (see photo).
- As the gas of choice for the plasma used in ICP spectroscopy
- As a non-reactive blanket in the processing of titanium and other reactive elements,
- As a protective atmosphere for growing silicon and germanium crystals, and in partial pressure heat treat furnaces.
- By museum conservators to protect old materials or documents, which are prone to gradual oxidation in the presence of air.
- To keep open bottles of wine from oxidizing, and in a number of dispensing units and keeper cap systems.
- In winemaking to top off barrels, displacing oxygen and thus preventing the wine from turning to vinegar during the aging process.
- In the pharmaceutical industry to top off bottles of intravenous drug preparations (for example intravenous paracetamol), again displacing oxygen and therefore prolonging the drug's shelf-life.
- Used to cool the seeker head of the US Air Force version of the AIM-9 Sidewinder missile. The gas is stored at high pressure, and the expansion of the gas cools the seeker.
The next most common reason for using argon is its low thermal conductivity. It is used for thermal insulation in energy efficient windows. Argon is also used in technical scuba diving to inflate a dry suit, because it is inert and has low thermal conductivity.
Argon is also used for the specific way it ionizes and emits light. It is used in plasma globes and calorimetry in experimental particle physics. Blue argon lasers are used in surgery to weld arteries, destroy tumors, and to correct eye defects. In microelectronics, argon ions are used for sputtering.
Finally, there are a number of miscellaneous uses. Argon-39, with a half life of 269 years, has been used for a number of applications, primarily ice core and ground water dating. The argon-40/potassium-40 ratio is used in dating igneous rocks.
Cryosurgery procedures such as cryoablation use liquified argon to destroy cancer cells. In surgery it is used in a procedure called "argon enhanced coagulation" which is a form of argon plasma beam electrosurgery. The procedure carries a risk of producing gas embolism in the patient and has resulted in the death of one person via this type of accident.
# Occurrence
Argon constitutes 0.934% by volume and 1.29% by mass of the Earth's atmosphere, and air is the primary raw material used by industry to produce purified argon products. Argon is isolated from air by fractionation, most commonly by cryogenic fractional distillation, a process that also produces purified nitrogen, oxygen, neon, krypton and xenon.
The Martian atmosphere in contrast contains 1.6% of argon-40 and 5 ppm of argon-36. The Mariner spaceprobe fly-by of the planet Mercury in 1973 found that Mercury has a very thin atmosphere with 70% argon, believed to result from releases of the gas as a decay product from radioactive materials on the planet. In 2005, the Huygens probe also discovered the presence of argon-40 on Titan, the largest moon of Saturn.
# Compounds
Argon’s complete octet of electrons indicates full s and p subshells. This full outer energy level makes argon very stable and extremely resistant to bonding with other elements. Before 1962, argon and the other noble gases were considered to be chemically inert and unable to form compounds; however, compounds of the heavier noble gases have since been synthesized. In August 2000, the first argon compounds were formed by researchers at the University of Helsinki. By shining ultraviolet light onto frozen argon containing a small amount of hydrogen fluoride, argon hydrofluoride (HArF) was formed. It is stable up to 40 kelvins (−233 °C).
The discovery of argon difluoride (ArF2) was announced in 2003. But this is unconfirmed and most probably incorrect.
# Isotopes
The main isotopes of argon found on Earth are 40Ar (99.6%), 36Ar (0.34%), and 38Ar (0.06%). Naturally occurring 40K with a half-life of 1.25Template:E years, decays to stable 40Ar (11.2%) by electron capture and positron emission, and also to stable 40Ca (88.8%) via beta decay. These properties and ratios are used to determine the age of rocks.
In the Earth's atmosphere, 39Ar is made by cosmic ray activity, primarily with 40Ar. In the subsurface environment, it is also produced through neutron capture by 39K or alpha emission by calcium. 37Ar is created from the decay of 40Ca as a result of subsurface nuclear explosions. It has a half-life of 35 days.
# Potential hazards
Although argon is non-toxic, it does not satisfy the body's need for oxygen and is a simple asphyxiant. People have suffocated by breathing argon by mistake. | Argon
Template:Infobox argon
# Overview
Argon (Template:PronEng) is a chemical element designated by the symbol Ar. Argon has atomic number 18 and is the third element in group 18 of the periodic table (noble gases). Argon is present in the Earth's atmosphere at slightly less than 1%, making it the most common noble gas on Earth. Its full outer shell makes argon stable and resistant to bonding with other elements. Its triple point temperature of 83.8058 K is a defining fixed point in the International Temperature Scale of 1990.
# Characteristics
Argon has approximately the same solubility in water as oxygen gas and is 2.5 times more soluble in water than nitrogen gas. This highly stable chemical element is colorless, odorless, tasteless and nontoxic in both its liquid and gaseous forms. Argon is inert under most conditions and forms no confirmed stable compounds at room temperature.
Although argon is a noble gas, it has been found to have the capability of forming some compounds. For example, the creation of argon hydrofluoride (HArF), a metastable compound of argon with fluorine and hydrogen, has been reported by researchers at the University of Helsinki in 2000.[1] Although the neutral ground-state chemical compounds of argon are presently limited to HArF, argon can form clathrates with water when atoms of it are trapped in a lattice of the water molecules.[2] Also argon-containing ions e.g. ArH+ and excited state complexes e.g. ArF are well known. Theoretical calculations on computers have shown several argon compounds that should be stable but for which no synthesis routes are currently known.
# History
Argon (Greek αργόν meaning "the lazy one," in reference to its chemical inactivity)[3][4][5] was suspected to be present in air by Henry Cavendish in 1785 but was not discovered until 1894 by Lord Rayleigh and Sir William Ramsay in an experiment in which they removed all of the oxygen and nitrogen from a sample of air.[6] Argon was also encountered in 1882 through independent research of H.F. Newall and W.N. Hartley. Each observed new lines in the color spectrum of air but were unable to identify the element responsible for the lines. Argon became the first member of the noble gases to be discovered. The symbol for argon is now Ar, but up until 1957 it was A.[7]
# Applications
There are several different reasons why argon is used in particular applications:
- An inert gas is needed. In particular, argon is the cheapest alternative when diatomic nitrogen is not sufficiently inert.
- Low thermal conductivity is required.
- The electronic properties (ionization and/or the emission spectrum) are necessary.
Other noble gases would probably work as well in most of these applications, but argon is by far the cheapest. Argon is inexpensive since it is a byproduct of the production of liquid oxygen and liquid nitrogen, both of which are used on a large industrial scale. The other noble gases (except helium) are produced this way as well, but argon is the most plentiful since it has the highest concentration in the atmosphere.
The bulk of argon applications arise simply because it is inert and relatively cheap. Argon is used:
- As a fill gas in incandescent lighting, because argon will not react with the filament of light bulbs even at high temperatures.
- As an inert gas shield in many forms of welding, including metal inert gas welding and tungsten inert gas welding.
- For extinguishing fires where damage to equipment is to be avoided (see photo).
- As the gas of choice for the plasma used in ICP spectroscopy
- As a non-reactive blanket in the processing of titanium and other reactive elements,
- As a protective atmosphere for growing silicon and germanium crystals, and in partial pressure heat treat furnaces.
- By museum conservators to protect old materials or documents, which are prone to gradual oxidation in the presence of air. [8]
- To keep open bottles of wine from oxidizing, and in a number of dispensing units and keeper cap systems.
- In winemaking to top off barrels, displacing oxygen and thus preventing the wine from turning to vinegar during the aging process.
- In the pharmaceutical industry to top off bottles of intravenous drug preparations (for example intravenous paracetamol), again displacing oxygen and therefore prolonging the drug's shelf-life.
- Used to cool the seeker head of the US Air Force version of the AIM-9 Sidewinder missile. The gas is stored at high pressure, and the expansion of the gas cools the seeker[9].
The next most common reason for using argon is its low thermal conductivity. It is used for thermal insulation in energy efficient windows.[10] Argon is also used in technical scuba diving to inflate a dry suit, because it is inert and has low thermal conductivity.
Argon is also used for the specific way it ionizes and emits light. It is used in plasma globes and calorimetry in experimental particle physics. Blue argon lasers are used in surgery to weld arteries, destroy tumors, and to correct eye defects.[11] In microelectronics, argon ions are used for sputtering.
Finally, there are a number of miscellaneous uses. Argon-39, with a half life of 269 years, has been used for a number of applications, primarily ice core and ground water dating. The argon-40/potassium-40 ratio is used in dating igneous rocks.
Cryosurgery procedures such as cryoablation use liquified argon to destroy cancer cells. In surgery it is used in a procedure called "argon enhanced coagulation" which is a form of argon plasma beam electrosurgery. The procedure carries a risk of producing gas embolism in the patient and has resulted in the death of one person via this type of accident. [12]
# Occurrence
Argon constitutes 0.934% by volume and 1.29% by mass of the Earth's atmosphere, and air is the primary raw material used by industry to produce purified argon products. Argon is isolated from air by fractionation, most commonly by cryogenic fractional distillation, a process that also produces purified nitrogen, oxygen, neon, krypton and xenon.[13]
The Martian atmosphere in contrast contains 1.6% of argon-40 and 5 ppm of argon-36. The Mariner spaceprobe fly-by of the planet Mercury in 1973 found that Mercury has a very thin atmosphere with 70% argon, believed to result from releases of the gas as a decay product from radioactive materials on the planet. In 2005, the Huygens probe also discovered the presence of argon-40 on Titan, the largest moon of Saturn.[14]
# Compounds
Argon’s complete octet of electrons indicates full s and p subshells. This full outer energy level makes argon very stable and extremely resistant to bonding with other elements. Before 1962, argon and the other noble gases were considered to be chemically inert and unable to form compounds; however, compounds of the heavier noble gases have since been synthesized. In August 2000, the first argon compounds were formed by researchers at the University of Helsinki. By shining ultraviolet light onto frozen argon containing a small amount of hydrogen fluoride, argon hydrofluoride (HArF) was formed.[15] It is stable up to 40 kelvins (−233 °C).
The discovery of argon difluoride (ArF2) was announced in 2003. But this is unconfirmed and most probably incorrect.
# Isotopes
The main isotopes of argon found on Earth are 40Ar (99.6%), 36Ar (0.34%), and 38Ar (0.06%). Naturally occurring 40K with a half-life of 1.25Template:E years, decays to stable 40Ar (11.2%) by electron capture and positron emission, and also to stable 40Ca (88.8%) via beta decay. These properties and ratios are used to determine the age of rocks.[16]
In the Earth's atmosphere, 39Ar is made by cosmic ray activity, primarily with 40Ar. In the subsurface environment, it is also produced through neutron capture by 39K or alpha emission by calcium. 37Ar is created from the decay of 40Ca as a result of subsurface nuclear explosions. It has a half-life of 35 days.[16]
# Potential hazards
Although argon is non-toxic, it does not satisfy the body's need for oxygen and is a simple asphyxiant. People have suffocated by breathing argon by mistake.[17] | https://www.wikidoc.org/index.php/Argon | |
5d1203a9f7a7a8242ea31ad00205d2da59c6008f | wikidoc | Joint | Joint
A joint is the location at which two or more bones make contact. They are constructed to allow movement and provide mechanical support, and are classified structurally and functionally.
# Classification
Joints are mainly classified structurally and functionally. Structural classification is determined by how the bones connect to each other, while functional classification is determined by the degree of movement between the articulating bones. In practice, there is significant overlap between the two types of classifications. In example, the highly mobile diarthroses are universally synovial joints (and in practice the two terms are used interchangeably) though the first term refers to the functional classification and the second to the structural classification.
Terms ending in the suffix -sis are singlular and refer to just one joint, while -ses is the suffix for pluralization.
## Structural classification
Structural classification names and divides joints according to how the bones are connected to each other. There are three structural classifications of joints:
Fibrous/Immovable - bones are connected by dense connective tissue, consisting mainly of collagen. The fibrous joints are further divided into three types:
- Sutures are found between bones of the skull. In fetal skulls the sutures are wide to allow slight movement during birth. They later become rigid (synarthrodial).
- Syndesmosis are found between long bones of the body, such as the radius and ulna in forearm and the fibula and tibia in leg. Unlike other fibrous joints, syndesmoses are moveable (amphiarthrodial), albeit not to such degree as synovial joints.
- Gomphosis is a joint between the root of a tooth and the sockets in the maxilla or mandible.
Cartilaginous - bones are connected entirely by cartilage. Cartilaginous joints allow more movement between bones than a fibrous joint but less than the highly mobile synovial joint. An example would be the joint between the manubrium and the sternum. Cartilaginous joints also forms the growth regions of immature long bones and the intervertebral discs of the spinal column.
- Primary cartilaginous joints - Known as "synchondroses". Bones are connected by hyaline cartilage or fibrocartilage, sometimes occurring between ossification centers. This cartilage may ossify with age. Examples in humans are the joint between the first rib and the manubrium of the sternum, and the "growth plates" between ossification centers in long bones. These joints usually allow no movement, or minimal movement in the case of the manubriosternal and first manubriocostal joints.
- Secondary cartilaginous joints - Known as "symphyses". Fibrocartilaginous joints, usually occurring in the midline. Examples in human anatomy would be the intervertebral discs, and the pubic symphysis. These joints allow a little movement.
Synovial - synovial joints have a space between the articulating bones for synovial fluid. This classification contains joints that are the most mobile of the three, and includes the knee and shoulder. These are further classified into ball and socket joints, condyloid joints, saddle joints, hinge joints, pivot joints, and gliding joints.
## Functional classification
Joints can also be classified functionally, by the degree of mobility they allow.
Synarthrosis - permit little or no mobility. Most synarthrosis joints are fibrous. They can be categorised by how the two bones are joined together:
- Synchondroses are joints where the two bones are connected by a piece of cartilage.
- Synostoses are where two bones that are initially separted eventually fuse together, essentially becoming one bone. In humans the plates of the cranium fuse together as a child approaches adulthood. Children whose craniums fuse too early may suffer deformities and brain damage as the skull does not expand properly to accommodate the growing brain, a condition known as craniostenosis.
Amphiarthrosis - permit slight mobility. The two bone surfaces at the joint are both covered in hyaline cartilage and joined by strands of fibrocartilage. Most amphiarthrosis joints are cartilaginous.
Diarthrosis - permit a variety of movements (e.g. flexion, adduction, pronation). Only synovial joints are diarthrodial. They can be divided into six classes:
- 1. Ball and Socket - such as the shoulder or the hip and femur.
- 2. Hinge - such as the elbow.
- 3. Pivot - such as the radius and ulna.
- 4. Condyloid (or ellipsoidal) - such as the wrist between radius and carpals, or knee
- 5. Saddle - such as the joint between carpal thumbs and metacarpals.
- 6. Gliding - such as between the carpals.
## Biomechanical classification
Joints can also be classified based on their anatomy or on their biomechanic properties. According to the anatomic classification, joints are subdivided into simple and compound, depending on the number of bones involved, and into complex and combination joints.
- Simple Joint: 2 articulation surfaces (eg. shoulder joint, hip joint)
- Compound Joint: 3 or more articulation surfaces (eg. radiocarpal joint)
- Complex Joint: 3 or more articulation surfaces AND an articular disc | Joint
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
A joint is the location at which two or more bones make contact. They are constructed to allow movement and provide mechanical support, and are classified structurally and functionally.
# Classification
Joints are mainly classified structurally and functionally. Structural classification is determined by how the bones connect to each other, while functional classification is determined by the degree of movement between the articulating bones. In practice, there is significant overlap between the two types of classifications. In example, the highly mobile diarthroses are universally synovial joints (and in practice the two terms are used interchangeably) though the first term refers to the functional classification and the second to the structural classification.
Terms ending in the suffix -sis are singlular and refer to just one joint, while -ses is the suffix for pluralization.
## Structural classification
Structural classification names and divides joints according to how the bones are connected to each other. There are three structural classifications of joints:
Fibrous/Immovable - bones are connected by dense connective tissue, consisting mainly of collagen. The fibrous joints are further divided into three types:
- Sutures are found between bones of the skull. In fetal skulls the sutures are wide to allow slight movement during birth. They later become rigid (synarthrodial).
- Syndesmosis are found between long bones of the body, such as the radius and ulna in forearm and the fibula and tibia in leg. Unlike other fibrous joints, syndesmoses are moveable (amphiarthrodial), albeit not to such degree as synovial joints.
- Gomphosis is a joint between the root of a tooth and the sockets in the maxilla or mandible.
Cartilaginous - bones are connected entirely by cartilage. Cartilaginous joints allow more movement between bones than a fibrous joint but less than the highly mobile synovial joint. An example would be the joint between the manubrium and the sternum. Cartilaginous joints also forms the growth regions of immature long bones and the intervertebral discs of the spinal column.
- Primary cartilaginous joints - Known as "synchondroses". Bones are connected by hyaline cartilage or fibrocartilage, sometimes occurring between ossification centers. This cartilage may ossify with age. Examples in humans are the joint between the first rib and the manubrium of the sternum, and the "growth plates" between ossification centers in long bones. These joints usually allow no movement, or minimal movement in the case of the manubriosternal and first manubriocostal joints.
- Secondary cartilaginous joints - Known as "symphyses". Fibrocartilaginous joints, usually occurring in the midline. Examples in human anatomy would be the intervertebral discs, and the pubic symphysis. These joints allow a little movement.
Synovial - synovial joints have a space between the articulating bones for synovial fluid. This classification contains joints that are the most mobile of the three, and includes the knee and shoulder. These are further classified into ball and socket joints, condyloid joints, saddle joints, hinge joints, pivot joints, and gliding joints.
## Functional classification
Joints can also be classified functionally, by the degree of mobility they allow.
Synarthrosis - permit little or no mobility. Most synarthrosis joints are fibrous. They can be categorised by how the two bones are joined together:
- Synchondroses are joints where the two bones are connected by a piece of cartilage.
- Synostoses are where two bones that are initially separted eventually fuse together, essentially becoming one bone. In humans the plates of the cranium fuse together as a child approaches adulthood. Children whose craniums fuse too early may suffer deformities and brain damage as the skull does not expand properly to accommodate the growing brain, a condition known as craniostenosis.
Amphiarthrosis - permit slight mobility. The two bone surfaces at the joint are both covered in hyaline cartilage and joined by strands of fibrocartilage. Most amphiarthrosis joints are cartilaginous.
Diarthrosis - permit a variety of movements (e.g. flexion, adduction, pronation). Only synovial joints are diarthrodial. They can be divided into six classes:
- 1. Ball and Socket - such as the shoulder or the hip and femur.
- 2. Hinge - such as the elbow.
- 3. Pivot - such as the radius and ulna.
- 4. Condyloid (or ellipsoidal) - such as the wrist between radius and carpals, or knee
- 5. Saddle - such as the joint between carpal thumbs and metacarpals.
- 6. Gliding - such as between the carpals.
## Biomechanical classification
Joints can also be classified based on their anatomy or on their biomechanic properties. According to the anatomic classification, joints are subdivided into simple and compound, depending on the number of bones involved, and into complex and combination joints.
- Simple Joint: 2 articulation surfaces (eg. shoulder joint, hip joint)
- Compound Joint: 3 or more articulation surfaces (eg. radiocarpal joint)
- Complex Joint: 3 or more articulation surfaces AND an articular disc | https://www.wikidoc.org/index.php/Articular_surface | |
e935a4c0f4460d06a10e67be1086d777e91f5aa7 | wikidoc | Aryne | Aryne
In chemistry, an aryne is an uncharged reactive intermediate derived from an aromatic system by removal of two ortho substituents, leaving two orbitals with two electrons distributed between them . In analogy with carbenes and nitrenes, an aryne has a singlet state and a triplet state. The name benzyne (1) C6H4 for the simplest aryne is open for criticism because it implies an alkyne bond which is not the case, a better name is dehydrobenzene. Benzyne is stabilized by resonance between structures 1 and 2—a better representation of the electronic structure is 3. The "extra" pi bond (4b) is localised and orthogonal to the other pi bonds making up the atomatic ring (4a). Benzyne can also be drawn as a diradical: the pi bond 4b splits homolytically, leaving one electron on each of the two atoms that are formally part of that bond.
Benzyne is an extremely reactive species due to the nature of its triple bond. In normal acetylenic species (such as the simplest, ethyne) the unhybridized p orbitals are parallel to one another above and below the molecular axis. This facilitates maximum orbital overlap. In benzyne, however, the p orbtials are distored to accommodate the triple bond within the ring system, reducing their effective overlap. A suitable chemical trap for benzyne is a cyclopentadiene.
Benzyne can be a ortho-, meta- and para-benzyne where the biradical can be a 1,2-, 1,3- and 1,4-biradical species respectively. Their energies in silico are respectively 106, 122, and 138 kcal/mole .. The 1,4-biradical species has been identified in the Bergman cyclization. Professor Maitland Jones of Princeton University has studied the interconversion of the ortho-, meta - and para-benzynes.
# Aryne chemistry
Arynes are prepared from electron deficient aromatic compounds (often aryl halides) in presence of a strong base. The most prominent aryne reactions are Diels-Alder reactions with dienes. Tetrabromobenzene reacts with butyllithium to the diaryne intermediate with furan to form a tetrahydroanthracene . The mixture of syn and anti conformers can be separated based on difference in methanol solubility.
Anthracene is converted to a triptycene by Diels-Alder reaction of an aryne with the central benzene ring . A pentiptycene is the anthracene analogue after reaction with the diaryne.
Aryne reactivity can also be extended to carbon to carbon insertion reactions into substrates that can react both as a nucleophile and as an electrophile with for instance a malonic acid ester . The precursor to benzyne in this reaction is 2-(Trimethylsilyl)phenyl triflate.
# Aryne interconversions
An ortho to meta-aryne conversion has been postulated to occur in the pyrolysis (900°C) of the phenyl substituted aryne precursor 1 to acenaphthylene 7.
This reaction takes place through several reactive intermediates: the aryne 2 is formed from phenyl substituted phthalic anhydride which rearranges with ring contraction to the vinylidene 3. This carbene gives a C-H insertion reaction to pentalene 4 and then a retro insertion to vinylidene 5. After a cis-trans isomerism to 6 a final insertion reaction gives the acenaphthylene. Evidence for a phenyl migration in aryne 2 from the o-aryne to the m-aryne is based on isotope scrambling. When the ipso carbon atom is replaced by 13C in the precursor molecule it will in the default mechanism again show up in the acenaphthylene in an ipso arene position. The presence of 13C in the bridge position can only be explained when 15% of 2 isomerizes to m-aryne A.
# Scope
Aryne chemistry has been applied to the synthesis of novel aryl amines in a tandem reaction including two Diels-Alder reactions with three benzyne molecules reacting to one imidazole molecule : | Aryne
In chemistry, an aryne is an uncharged reactive intermediate derived from an aromatic system by removal of two ortho substituents, leaving two orbitals with two electrons distributed between them [1]. In analogy with carbenes and nitrenes, an aryne has a singlet state and a triplet state. The name benzyne (1) C6H4 for the simplest aryne is open for criticism because it implies an alkyne bond which is not the case, a better name is dehydrobenzene. Benzyne is stabilized by resonance between structures 1 and 2—a better representation of the electronic structure is 3. The "extra" pi bond (4b) is localised and orthogonal to the other pi bonds making up the atomatic ring (4a). Benzyne can also be drawn as a diradical: the pi bond 4b splits homolytically, leaving one electron on each of the two atoms that are formally part of that bond.
Benzyne is an extremely reactive species due to the nature of its triple bond. In normal acetylenic species (such as the simplest, ethyne) the unhybridized p orbitals are parallel to one another above and below the molecular axis. This facilitates maximum orbital overlap. In benzyne, however, the p orbtials are distored to accommodate the triple bond within the ring system, reducing their effective overlap. A suitable chemical trap for benzyne is a cyclopentadiene.
Benzyne can be a ortho-, meta- and para-benzyne where the biradical can be a 1,2-, 1,3- and 1,4-biradical species respectively. Their energies in silico are respectively 106, 122, and 138 kcal/mole .[2]. The 1,4-biradical species has been identified in the Bergman cyclization. Professor Maitland Jones of Princeton University has studied the interconversion of the ortho-, meta - and para-benzynes.[2][3]
# Aryne chemistry
Arynes are prepared from electron deficient aromatic compounds (often aryl halides) in presence of a strong base. The most prominent aryne reactions are Diels-Alder reactions with dienes. Tetrabromobenzene reacts with butyllithium to the diaryne intermediate with furan to form a tetrahydroanthracene [4]. The mixture of syn and anti conformers can be separated based on difference in methanol solubility.
Anthracene is converted to a triptycene by Diels-Alder reaction of an aryne with the central benzene ring [5]. A pentiptycene is the anthracene analogue after reaction with the diaryne.
Aryne reactivity can also be extended to carbon to carbon insertion reactions into substrates that can react both as a nucleophile and as an electrophile with for instance a malonic acid ester [6]. The precursor to benzyne in this reaction is 2-(Trimethylsilyl)phenyl triflate.
# Aryne interconversions
An ortho to meta-aryne conversion has been postulated to occur in the pyrolysis (900°C) of the phenyl substituted aryne precursor 1 [2] to acenaphthylene 7.
This reaction takes place through several reactive intermediates: the aryne 2 is formed from phenyl substituted phthalic anhydride which rearranges with ring contraction to the vinylidene 3. This carbene gives a C-H insertion reaction to pentalene 4 and then a retro insertion to vinylidene 5. After a cis-trans isomerism to 6 a final insertion reaction gives the acenaphthylene. Evidence for a phenyl migration in aryne 2 from the o-aryne to the m-aryne is based on isotope scrambling. When the ipso carbon atom is replaced by 13C in the precursor molecule it will in the default mechanism again show up in the acenaphthylene in an ipso arene position. The presence of 13C in the bridge position can only be explained when 15% of 2 isomerizes to m-aryne A.
# Scope
Aryne chemistry has been applied to the synthesis of novel aryl amines in a tandem reaction including two Diels-Alder reactions with three benzyne molecules reacting to one imidazole molecule [7]: | https://www.wikidoc.org/index.php/Aryne | |
4be281f7136623d34db6f65416347a7540834014 | wikidoc | Assay | Assay
# Overview
An assay is a procedure where a property or concentration of an analyte is measured.
There are numerous types of assays, such as an antigen capture assay, bioassay, competitive protein binding assay, crude oil assay, four-point assay, immunoassay, microbiological assay, stem cell assay, and many others, including concentration assays.
# Molecular biology assays
Assays are regularly utilized in molecular biology scientific research laboratories.
## DNA
Assays for studying interactions of proteins with DNA include:
- DNase footprinting assay
- filter binding assay
- gel shift assay
## RNA
- nuclear run-on
## Protein
- Bicinchoninic acid assay (better known as the BCA assay)
- Bradford protein assay
- Lowry protein assay
- Secretion assay
## Cytotoxicity
Assays for studying how toxic a compound is to cells:
- MTT assay
- SRB (Sulforhodamine B) assay
## Viruses
- Viral plaque assay: Used to calculate the number of viruses present in a sample. This technique requires counting the number of plaques formed by a virus sample, from which the actual virus concentration can be determined.
- Trofile assay: Used to determine HIV tropism.
## Cellular secretions
A wide range of cellular secretions (say, a specific antibody or cytokine) can be detected using the ELISA technique. The number of cells which secrete those particular substances can be determined using a related technique, the ELISPOT assay.
## Drugs
Illegal drug testing
# Environmental contaminants
- Lead
- Coliform bacteria
- Arsenic
# Methods of assay of precious metals
There are methods of assay suitable for use on raw materials and other methods which are more properly suited for finished goods. Raw precious metals (bullion) are assayed by an assay office. Silver is assayed by titration, gold by cupellation and platinum by inductively coupled plasma optical emission spectrometry (ICP OES).,
Precious metal items of art or jewelry are frequently hallmarked (depending upon the requirements of the laws of either the place of manufacture or the place of import). Where required to be hallmarked, semi-finished precious metal items of art or jewelry pass through the official testing channels where they are analyzed or assayed for precious metal content. While different nations permit a variety of legally acceptable finenesses, the assayer is actually testing to determine that the fineness of the product conforms with the statement or claim of fineness that the maker has claimed (usually by stamping a number such as 750 for 18k gold) on the item. In the past the assay was conducted by using the touchstone method but currently (most often) it is done using X-ray Fluorescence (XRF). XRF is used because this method is more exacting than the touchstone test. The most exact method of assay is known as fire assay or cupellation. This method is better suited for the assay of bullion and gold stocks rather than works or art or jewelry because it is a completely destructive method.
## The touchstone
The age-old touchstone method is particularly suited to the testing of very valuable pieces, for which sampling by destructive means, such as scrapping, cutting or drilling is unacceptable. A rubbing of the item is made on a special stone, treated with acids and the resulting color compared to references. Differences in precious metal content as small as 10 to 20 parts per thousand can often be established with confidence by the test. It is not indicated for use with white gold, for example, since the color variation among white gold alloys is almost unperceivable.
## X-ray fluorescence
The modern X-ray fluorescence is also a non-destructive technique that is suitable for normal assaying requirements. It typically has an accuracy of 2 to 5 parts per thousand and is well-suited to the relatively flat and large surfaces. It is a quick technique taking about three minutes, and the results can be automatically printed out by computer. It also measures the content of the other alloying metals present. It is not indicated, however, for articles with chemical surface treatment or electroplating.
## Fire assay/cupellation
The most elaborate but totally destructive assay method is fire-assay,also called cupellation, with an accuracy of 1 part in 10,000. In this process the article is melted, the alloys separated and constituents weighed.
# The assay of coins
An assayer is often assigned to each mint or assay office to determine and assure that all coins produced at the mint have the correct content or purity of each metal specified, usually by law, to be contained in them. This was particularly important when gold and silver coins were produced for circulation and used in daily commerce. Few nations, however, persist in minting silver or gold coins for general circulation. For example the U.S. discontinued the use of gold in coinage in 1933. The U.S. was perhaps the last nation to discontinue the use of silver in circulating coins in its 1969 half dollar coin, although the amount of silver used in smaller denomination coins was ended after 1964. Even with the half dollar, the amount of silver used in the coins was reduced from 90% in 1964 and earlier to 40% between 1965 and 1969. Copper, nickel, cupro-nickel and brass alloys now predominate in coin making. Notwithstanding, several national mints, including the Australian Mint at Perth, the Austrian Mint, the British Royal Mint, the Royal Canadian Mint, the South African Mint and the U.S. Mint continue to produce precious metal bullion coins for collectors and investors. The precious metal purity and content of these coins is guaranteed by the respective mint or government and therefore the assay of the raw materials and finished coins is an important quality control.
In the UK the Trial of the Pyx is a ceremonial procedure for ensuring that newly-minted coins conform to required standards. | Assay
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
# Overview
An assay is a procedure where a property or concentration of an analyte is measured.
There are numerous types of assays, such as an antigen capture assay, bioassay, competitive protein binding assay, crude oil assay, four-point assay, immunoassay, microbiological assay, stem cell assay, and many others, including concentration assays.
# Molecular biology assays
Assays are regularly utilized in molecular biology scientific research laboratories.
## DNA
Assays for studying interactions of proteins with DNA include:
- DNase footprinting assay
- filter binding assay
- gel shift assay
## RNA
- nuclear run-on
## Protein
- Bicinchoninic acid assay (better known as the BCA assay)
- Bradford protein assay
- Lowry protein assay
- Secretion assay
## Cytotoxicity
Assays for studying how toxic a compound is to cells:
- MTT assay
- SRB (Sulforhodamine B) assay
## Viruses
- Viral plaque assay: Used to calculate the number of viruses present in a sample. This technique requires counting the number of plaques formed by a virus sample, from which the actual virus concentration can be determined.
- Trofile assay: Used to determine HIV tropism.
## Cellular secretions
A wide range of cellular secretions (say, a specific antibody or cytokine) can be detected using the ELISA technique. The number of cells which secrete those particular substances can be determined using a related technique, the ELISPOT assay.
## Drugs
Illegal drug testing
# Environmental contaminants
- Lead
- Coliform bacteria
- Arsenic
# Methods of assay of precious metals
There are methods of assay suitable for use on raw materials and other methods which are more properly suited for finished goods. Raw precious metals (bullion) are assayed by an assay office. Silver is assayed by titration, gold by cupellation and platinum by inductively coupled plasma optical emission spectrometry (ICP OES).[1],[2]
Precious metal items of art or jewelry are frequently hallmarked (depending upon the requirements of the laws of either the place of manufacture or the place of import). Where required to be hallmarked, semi-finished precious metal items of art or jewelry pass through the official testing channels where they are analyzed or assayed for precious metal content. While different nations permit a variety of legally acceptable finenesses, the assayer is actually testing to determine that the fineness of the product conforms with the statement or claim of fineness that the maker has claimed (usually by stamping a number such as 750 for 18k gold) on the item. In the past the assay was conducted by using the touchstone method but currently (most often) it is done using X-ray Fluorescence (XRF). XRF is used because this method is more exacting than the touchstone test. The most exact method of assay is known as fire assay or cupellation. This method is better suited for the assay of bullion and gold stocks rather than works or art or jewelry because it is a completely destructive method.
## The touchstone
The age-old touchstone method is particularly suited to the testing of very valuable pieces, for which sampling by destructive means, such as scrapping, cutting or drilling is unacceptable. A rubbing of the item is made on a special stone, treated with acids and the resulting color compared to references. Differences in precious metal content as small as 10 to 20 parts per thousand can often be established with confidence by the test. It is not indicated for use with white gold, for example, since the color variation among white gold alloys is almost unperceivable.
## X-ray fluorescence
The modern X-ray fluorescence is also a non-destructive technique that is suitable for normal assaying requirements. It typically has an accuracy of 2 to 5 parts per thousand and is well-suited to the relatively flat and large surfaces. It is a quick technique taking about three minutes, and the results can be automatically printed out by computer. It also measures the content of the other alloying metals present. It is not indicated, however, for articles with chemical surface treatment or electroplating.
## Fire assay/cupellation
The most elaborate but totally destructive assay method is fire-assay,also called cupellation, with an accuracy of 1 part in 10,000. In this process the article is melted, the alloys separated and constituents weighed.
# The assay of coins
An assayer is often assigned to each mint or assay office to determine and assure that all coins produced at the mint have the correct content or purity of each metal specified, usually by law, to be contained in them. This was particularly important when gold and silver coins were produced for circulation and used in daily commerce. Few nations, however, persist in minting silver or gold coins for general circulation. For example the U.S. discontinued the use of gold in coinage in 1933. The U.S. was perhaps the last nation to discontinue the use of silver in circulating coins in its 1969 half dollar coin, although the amount of silver used in smaller denomination coins was ended after 1964. Even with the half dollar, the amount of silver used in the coins was reduced from 90% in 1964 and earlier to 40% between 1965 and 1969. Copper, nickel, cupro-nickel and brass alloys now predominate in coin making. Notwithstanding, several national mints, including the Australian Mint at Perth, the Austrian Mint, the British Royal Mint, the Royal Canadian Mint, the South African Mint and the U.S. Mint continue to produce precious metal bullion coins for collectors and investors. The precious metal purity and content of these coins is guaranteed by the respective mint or government and therefore the assay of the raw materials and finished coins is an important quality control.
In the UK the Trial of the Pyx is a ceremonial procedure for ensuring that newly-minted coins conform to required standards. | https://www.wikidoc.org/index.php/Assay | |
65d25c1f76ae3e43bf719b38c3923e861854a047 | wikidoc | Asset | Asset
In business and accounting by asset is meant probable future economic benefits controlled by an entity as a result of past transactions or events and from which future economic benefits may be obtained.
# Asset characteristics
Assets have three essential characteristics:
- They embody a future benefit that involves a capacity, singly or in combination with other assets, in the case of profit oriented enterprises, to contribute directly or indirectly to future net cash flows, and, in the case of not-for-profit organizations, to provide services;
- The entity can control access to the benefit; and,
- The transaction or event giving rise to the entity's right to, or control of, the benefit has already occurred.
It is not necessary, in the financial accounting sense of the term, for control of access to the benefit to be legally enforceable for a resource to be an asset, provided the entity can control its use by other means.
It is important to understand that in an accounting sense an asset is not the same as ownership. In accounting, ownership is described by the term "equity," (see the related term shareholders' equity). Assets are equal to "equity" plus "liabilities."
The accounting equation relates assets, liabilities, and owner's equity:
The accounting equation is the mathematical structure of the balance sheet.
Assets are usually listed on the balance sheet. It has a normal balance, or usual balance, of debit (i.e., asset account amounts appear on the left side of a ledger).
Similarly, in economics an asset is any form in which wealth can be held.
Probably the most accepted accounting definition of asset is the one used by the International Accounting Standards Board . The following is a quotation from the IFRS Framework: "An asset is a resource controlled by the enterprise as a result of past events and from which future economic benefits are expected to flow to the enterprise."
Assets are formally controlled and managed within larger organizations via the use of asset tracking tools. These monitor the purchasing, upgrading, servicing, licensing, disposal etc., of both physical and non-physical assets.
# Classification of assets
Assets may be classified in many ways. In a company's balance sheet certain divisions are required by generally accepted accounting principles (GAAP), which vary from country to country.
Current assets are cash and other assets expected to be converted to cash, sold, or consumed either in a year or in the operating cycle. These assets are continually turned over in the course of a business during normal business activity. There are 5 major items included into current assets:
- Cash — it is the most liquid asset, which includes currency, deposit accounts, and negotiable instruments (e.g., money orders, cheque, bank drafts).
- Short-term investments — include securities bought and held for sale in the near future to generate income on short-term price differences (trading securities).
- Receivables — usually reported as net of allowance for uncollectible accounts.
- Inventory — trading these assets is a normal business of a company. The inventory value reported on the balance sheet is usually the historical cost or fair market value, whichever is lower. This is known as the "lower of cost or market" rule.
- Prepaid expenses — these are expenses paid in cash and recorded as assets before they are used or consumed (a common example is insurance). See also adjusting entries.
The phrase net current assets (also called working capital) is often used and refers to the total of current assets less the total of current liabilities.
### Long-term investments
Often referred to simply as "investments." Long-term investments are to be held for many years and are not intended to be disposed in the near future. This group usually consists of four types of investments:
- Investments in securities, such as bonds, common stock, or long-term notes.
- Investments in fixed assets not used in operations (e.g., land held for sale).
- Investments in special funds (e.g., sinking funds or pension funds).
- Investments in subsidiaries or affiliated companies.
Different forms of insurance may also be treated as long term investments.
### Fixed assets
Also referred to as PPE (property, plant, and equipment), or tangible assets, these are purchased for continued and long-term use in earning profit in a business. This group includes land, buildings, machinery, furniture, tools, and certain wasting resources e.g., timberland and minerals. They are written off against profits over their anticipated life by charging depreciation expenses (with exception of land). Accumulated depreciation is shown in the face of the balance sheet or in the notes.
These are also called capital assets in management accounting.
### Intangible assets
Intangible assets lack physical substance and usually are very hard to evaluate. They include patents, copyrights, franchises, goodwill, trademarks, trade names, etc. These assets are (according to US GAAP) amortized to expense over 5 to 40 years with the exception of goodwill.
Some assets such as websites are treated differently in different countries and may fall under either tangible or intangible assets.
### Other assets
This section includes a high variety of assets, most commonly:
- long-term prepaid expenses
- long-term receivables
- intangible assets (if they represent just a very small fraction of total assets)
- property held for sale.
In a lot of cases this section is too general and broad, because assets could be classified into four above categories. | Asset
Template:Otheruses1
In business and accounting by asset is meant probable future economic benefits controlled by an entity as a result of past transactions or events and from which future economic benefits may be obtained.
# Asset characteristics
Assets have three essential characteristics:
- They embody a future benefit that involves a capacity, singly or in combination with other assets, in the case of profit oriented enterprises, to contribute directly or indirectly to future net cash flows, and, in the case of not-for-profit organizations, to provide services;
- The entity can control access to the benefit; and,
- The transaction or event giving rise to the entity's right to, or control of, the benefit has already occurred.
It is not necessary, in the financial accounting sense of the term, for control of access to the benefit to be legally enforceable for a resource to be an asset, provided the entity can control its use by other means.
It is important to understand that in an accounting sense an asset is not the same as ownership. In accounting, ownership is described by the term "equity," (see the related term shareholders' equity). Assets are equal to "equity" plus "liabilities."
The accounting equation relates assets, liabilities, and owner's equity:
The accounting equation is the mathematical structure of the balance sheet.
Assets are usually listed on the balance sheet. It has a normal balance, or usual balance, of debit (i.e., asset account amounts appear on the left side of a ledger).
Similarly, in economics an asset is any form in which wealth can be held.
Probably the most accepted accounting definition of asset is the one used by the International Accounting Standards Board [1]. The following is a quotation from the IFRS Framework: "An asset is a resource controlled by the enterprise as a result of past events and from which future economic benefits are expected to flow to the enterprise." [2]
Assets are formally controlled and managed within larger organizations via the use of asset tracking tools. These monitor the purchasing, upgrading, servicing, licensing, disposal etc., of both physical and non-physical assets.
# Classification of assets
Assets may be classified in many ways. In a company's balance sheet certain divisions are required by generally accepted accounting principles (GAAP), which vary from country to country.
Current assets are cash and other assets expected to be converted to cash, sold, or consumed either in a year or in the operating cycle. These assets are continually turned over in the course of a business during normal business activity. There are 5 major items included into current assets:
- Cash — it is the most liquid asset, which includes currency, deposit accounts, and negotiable instruments (e.g., money orders, cheque, bank drafts).
- Short-term investments — include securities bought and held for sale in the near future to generate income on short-term price differences (trading securities).
- Receivables — usually reported as net of allowance for uncollectible accounts.
- Inventory — trading these assets is a normal business of a company. The inventory value reported on the balance sheet is usually the historical cost or fair market value, whichever is lower. This is known as the "lower of cost or market" rule.
- Prepaid expenses — these are expenses paid in cash and recorded as assets before they are used or consumed (a common example is insurance). See also adjusting entries.
The phrase net current assets (also called working capital) is often used and refers to the total of current assets less the total of current liabilities.
### Long-term investments
Often referred to simply as "investments." Long-term investments are to be held for many years and are not intended to be disposed in the near future. This group usually consists of four types of investments:
- Investments in securities, such as bonds, common stock, or long-term notes.
- Investments in fixed assets not used in operations (e.g., land held for sale).
- Investments in special funds (e.g., sinking funds or pension funds).
- Investments in subsidiaries or affiliated companies.
Different forms of insurance may also be treated as long term investments.
### Fixed assets
Also referred to as PPE (property, plant, and equipment), or tangible assets, these are purchased for continued and long-term use in earning profit in a business. This group includes land, buildings, machinery, furniture, tools, and certain wasting resources e.g., timberland and minerals. They are written off against profits over their anticipated life by charging depreciation expenses (with exception of land). Accumulated depreciation is shown in the face of the balance sheet or in the notes.
These are also called capital assets in management accounting.
### Intangible assets
Intangible assets lack physical substance and usually are very hard to evaluate. They include patents, copyrights, franchises, goodwill, trademarks, trade names, etc. These assets are (according to US GAAP) amortized to expense over 5 to 40 years with the exception of goodwill.
Some assets such as websites are treated differently in different countries and may fall under either tangible or intangible assets.
### Other assets
This section includes a high variety of assets, most commonly:
- long-term prepaid expenses
- long-term receivables
- intangible assets (if they represent just a very small fraction of total assets)
- property held for sale.
In a lot of cases this section is too general and broad, because assets could be classified into four above categories. | https://www.wikidoc.org/index.php/Asset | |
6d2505504a78e909b65ff9b607a7817a7e99439c | wikidoc | Atmit | Atmit
Atmit is a nutritional supplement used to fight famine in impoverished countries. The creamy, nutritious food is indigenous to Ethiopia and is now used to feed the severely malnourished and weakened adults and children. The word atmit originated in Ethiopia and means "thin, nourishing porridge."
Atmit is made from rolled oats, powdered milk, powdered sugar, vitamins, and minerals. It is easily digestible, high in protein and calorie content. Since severely malnourished people cannot eat solid food, atmit is an ideal way to get them essential nutrients.
Marta Gabre-Tsadick, the first woman Senator from Ethiopia and the co-founder of Project Mercy, Inc., a Christian relief organization, adapted the recipe for production in the USA for shipment to Ethiopia and other African countries. During 1985 and 1986, Project Mercy sent 930 tons of atmit to Ethiopia, where World Vision relief workers used it to prepare millions of hot, nutritious meals which helped strengthen many people weakened from the famine.
Charity and relief organizations have created various formulas for this porridge. The Church of Jesus Christ of Latter-day Saints formula of atmit, which was sent in 2005 to Niger was made of the following:
- 50% Fine oatmeal flour
- 25% Nonfat milk
- 20% Sugar
- 5% Vitamins and minerals
Recently, atmit has been distributed to Uganda, Sudan, South Africa, Haiti, Gaza, Bangladesh, Indonesia, Sri Lanka and Niger.
# Reference
- "Atmit to the Rescue". Ensign: The Church of Jesus Christ of Latter-day Saints. January 2006. pp. 74–75..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} | Atmit
Atmit is a nutritional supplement used to fight famine in impoverished countries. The creamy, nutritious food is indigenous to Ethiopia and is now used to feed the severely malnourished and weakened adults and children. The word atmit originated in Ethiopia and means "thin, nourishing porridge."
Atmit is made from rolled oats, powdered milk, powdered sugar, vitamins, and minerals. It is easily digestible, high in protein and calorie content. Since severely malnourished people cannot eat solid food, atmit is an ideal way to get them essential nutrients.
Marta Gabre-Tsadick, the first woman Senator from Ethiopia and the co-founder of Project Mercy, Inc., a Christian relief organization, adapted the recipe for production in the USA for shipment to Ethiopia and other African countries. During 1985 and 1986, Project Mercy sent 930 tons of atmit to Ethiopia, where World Vision relief workers used it to prepare millions of hot, nutritious meals which helped strengthen many people weakened from the famine.
Charity and relief organizations have created various formulas for this porridge. The Church of Jesus Christ of Latter-day Saints formula of atmit, which was sent in 2005 to Niger was made of the following:
- 50% Fine oatmeal flour
- 25% Nonfat milk
- 20% Sugar
- 5% Vitamins and minerals
Recently, atmit has been distributed to Uganda, Sudan, South Africa, Haiti, Gaza, Bangladesh, Indonesia, Sri Lanka and Niger.
# Reference
- "Atmit to the Rescue". Ensign: The Church of Jesus Christ of Latter-day Saints. January 2006. pp. 74–75..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/Atmit | |
5e99c9e8626f4559fff06ea471bbbb997d22b2b9 | wikidoc | Atopy | Atopy
# Overview
Atopy (Greek ατοπία - placelessness) or atopic syndrome is an allergic hypersensitivity affecting parts of the body not in direct contact with the allergen. It may involve eczema (atopic dermatitis), allergic conjunctivitis, allergic rhinitis and asthma. There appears to be a strong hereditary component. One study concludes that "the general risk of developing atopic dermatitis (3%) and atopy (7%) increases by a factor of two with each first-degree family member already suffering from atopy"
The hereditary component is presumably due to certain genes coding proteins involved in the normal immune response mechanism, i.e., human leukocyte antigen, although environmental factors have also been implicated. Atopic syndrome can be fatal for those who experience serious allergic reactions such as anaphylaxis, brought on by reactions to food or environment.
The individual components are all caused at least in part by allergy (type I hypersensitivity reactions). These responses appear after the body is exposed to various allergens, for example specific kinds of food, pollen, dander or insect venoms. Although atopy has various definitions, most consistently it is defined by the presence of elevated levels of total and allergen-specific IgE in the serum of patient, leading to positive skin-prick tests to common allergens.
The multicenter PARSIFAL study in 2006, involving 6630 children age 5 to 13 in 5 European countries, suggested that restrictive use of antibiotics and antipyretics, are associated with a reduced risk of allergic disease in children.
Some symptoms, from an atopy questionnaire:
- Cracks in the skin under the earlobe
- Eczema
In elbow flexures and/or hollow of the knees
Nipple eczema
Neurodermatitis
Subtype Dyshidrosis
- In elbow flexures and/or hollow of the knees
- Nipple eczema
- Neurodermatitis
- Subtype Dyshidrosis
- Keratosis pilaris
- Perlèche
- Conjunctivitis
- Chronic or seasonal rhinitis
# Atopic diseases of childhood
The atopic diseases of childhood consist of atopic dermatitis, allergic rhinitis, and asthma. | Atopy
Template:DiseaseDisorder infobox
# Overview
Atopy (Greek ατοπία - placelessness) or atopic syndrome is an allergic hypersensitivity affecting parts of the body not in direct contact with the allergen. It may involve eczema (atopic dermatitis), allergic conjunctivitis, allergic rhinitis and asthma. There appears to be a strong hereditary component. One study concludes that "the general risk of developing atopic dermatitis (3%) and atopy (7%) increases by a factor of two with each first-degree family member already suffering from atopy"
[1].
The hereditary component is presumably due to certain genes coding proteins involved in the normal immune response mechanism, i.e., human leukocyte antigen, although environmental factors have also been implicated. Atopic syndrome can be fatal for those who experience serious allergic reactions such as anaphylaxis, brought on by reactions to food or environment.
The individual components are all caused at least in part by allergy (type I hypersensitivity reactions). These responses appear after the body is exposed to various allergens, for example specific kinds of food, pollen, dander or insect venoms. Although atopy has various definitions, most consistently it is defined by the presence of elevated levels of total and allergen-specific IgE in the serum of patient, leading to positive skin-prick tests to common allergens.
The multicenter PARSIFAL study in 2006, involving 6630 children age 5 to 13 in 5 European countries, suggested that restrictive use of antibiotics and antipyretics, are associated with a reduced risk of allergic disease in children.[2]
Some symptoms, from an atopy questionnaire[3]:
- Cracks in the skin under the earlobe
- Eczema
In elbow flexures and/or hollow of the knees
Nipple eczema
Neurodermatitis
Subtype Dyshidrosis
- In elbow flexures and/or hollow of the knees
- Nipple eczema
- Neurodermatitis
- Subtype Dyshidrosis
- Keratosis pilaris
- Perlèche
- Conjunctivitis
- Chronic or seasonal rhinitis
# Atopic diseases of childhood
The atopic diseases of childhood consist of atopic dermatitis, allergic rhinitis, and asthma. | https://www.wikidoc.org/index.php/Atopic | |
c2dca35d58259c1592d286b22b23b3d7e8038f91 | wikidoc | Pinna | Pinna
Please Take Over This Page and Apply to be Editor-In-Chief for this topic:
There can be one or more than one Editor-In-Chief. You may also apply to be an Associate Editor-In-Chief of one of the subtopics below. Please mail us to indicate your interest in serving either as an Editor-In-Chief of the entire topic or as an Associate Editor-In-Chief for a subtopic. Please be sure to attach your CV and or biographical sketch.
# Overview
The pinna (Latin for feather) is the visible part of the ear that resides outside of the head (this may also be referred to as the auricle or auricula).
# Purpose
The purpose of the pinna is to collect sound. It does so by acting as a funnel, amplifying the sound and directing it to the ear canal. While reflecting from the pinna, sound also goes through a filtering process which adds directional information to the sound (see sound localization, head-related transfer function, pinna notch). The filtering effect of the human pinna preferentially selects sounds in the frequency range of human speech.
# Amplification
Amplification of sound by the pinna, tympanic membrane and middle ear causes an increase in level of about 10 to 15 dB in a frequency range of 1.5 kHz to 7 kHz. This amplification is an important factor in inner ear trauma resulting
from elevated sound levels.
# Pinna Notch
The pinna works differently for low and high frequency sounds. For low frequencies, it behaves similarly to a reflector dish, directing sounds toward the ear canal. For high frequencies, however, its value is more sophisticatedly reckoned. While some of the sounds that enter the ear travel directly to the canal, others reflect off the contours of the pinna first: these enter the ear canal at a very slight delay. Such a delay translates into phase cancellation, where the frequency component whose wave period is twice the delay period is virtually eliminated. Neighboring frequencies are dropped significantly. This is known as the pinna notch, where the pinna creates a notch filtering effect.
# Anatomy
The diagram shows the shape and location of these components:
- Anthelix (antihelix) forms a 'Y' shape where the upper parts are:
Superior crux (to the left of the fossa triangularis in the diagram)
Inferior crux (to the right of the fossa triangularis in the diagram)
- Superior crux (to the left of the fossa triangularis in the diagram)
- Inferior crux (to the right of the fossa triangularis in the diagram)
- Antitragus is below the tragus
- Auricular sulcus is the depression behind the ear next to the head
- Concha is the hollow next to the ear canal
- Conchal angle is the angle that the back of the concha makes with the side of the head
- Crus of the helix is just above the tragus
- Cymba conchae is the narrowest end of the concha
- External auditory meatus is the opening to the ear canal
- Fossa triangularis is the depression in the fork of the anthelix
- Helix is the folded over outside edge of the ear
- Incisura anterior (auris) is between the tragus and the antitragus
- Lobe (lobule) - attached or free according to a classic single-gene dominance relationship
- Scapha
- Tragus
# Embryology
The developing Pinna is first noticeable around the sixth week of gestation in the human foetus, developing from six rounded protuberances (the six hillocks of Hiss) which are derived from the first and second branchial arches.
These hillocks develop into the folds of the pinna and gradually shift upwards and backwards to their final position on the head. En-route accessory auricles (also known as preauricular tags - see below) may be left behind.
The first three Hillocks are dervied from the 1st branchial arch and form the tragus, crus of the helix and helix respectively. Cutaneous sensation to these areas is via the trigeminal nerve, the attendant nerve of the 1st branchial arch.
The final three Hillockes are derived from the 2nd branchial arch and form the antihelix, antitragus and lobule respectively. These portions of the ear are supplied by the cervical plexus and a small portion by the facial nerve. This explains why vesicles are classically seen on the Pinna in Herpes infection of the facial nerve ( Ramsay-Hunt Syndrome)
# Abnormalities
There are various visible ear abnormalities:
- Bat ear (also known as wingnut ear) — an ear that protrudes
- Cryptotia (hidden ear) — upper auricular sulcus not visible
- Cup deformity — helical rim is compressed
- Darwinian tubercle (auricular tubercle) — a projection from the helical rim
- Lop ear — the top of the helical rim folded over
- Macrotia (also known as big ears, or hypertrophy of the ears)
- Microtia (small or partially developed ears)
- Preauricular sinus (small holes usually visible from birth at the front of the ears where the pinna joins the head)
- Accessory Auricles (small pieces of skin at the front of the ears where the pinna joins the head, vestigial remnants of the developing ears migration to it's final position)
- Rim kinks — a kink of the helical rim
- Selhurst's handle (also known as cup handle) — an ear that can be 50% larger than normal.
- Stahl’s bar (also known as Spock ear) — third crus (in between the superior crux and inferior crux) making the top of the ear pointed
- Zaheer's ear — having a deformed anti-tragus, which appears as a bump, as opposed to a protrusion, which would normally allow the snug insertion of earbud headphones
- Congenital Pit of the Cymba Conchae — This is a blind cavity that does not communicate with the external auditory canal. It occasionally fills with sebaceous material, desquamated skin or debris and requires cleaning or "scooping" with a wax curette .
# Additional images
- External and middle ear, opened from the front. Right side.
- Left ear | Pinna
Template:Infobox Anatomy
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Please Take Over This Page and Apply to be Editor-In-Chief for this topic:
There can be one or more than one Editor-In-Chief. You may also apply to be an Associate Editor-In-Chief of one of the subtopics below. Please mail us [2] to indicate your interest in serving either as an Editor-In-Chief of the entire topic or as an Associate Editor-In-Chief for a subtopic. Please be sure to attach your CV and or biographical sketch.
# Overview
The pinna (Latin for feather) is the visible part of the ear that resides outside of the head (this may also be referred to as the auricle or auricula).
# Purpose
The purpose of the pinna is to collect sound. It does so by acting as a funnel, amplifying the sound and directing it to the ear canal. While reflecting from the pinna, sound also goes through a filtering process which adds directional information to the sound (see sound localization, head-related transfer function, pinna notch). The filtering effect of the human pinna preferentially selects sounds in the frequency range of human speech.
# Amplification
Amplification of sound by the pinna, tympanic membrane and middle ear causes an increase in level of about 10 to 15 dB in a frequency range of 1.5 kHz to 7 kHz. This amplification is an important factor in inner ear trauma resulting
from elevated sound levels.
# Pinna Notch
The pinna works differently for low and high frequency sounds. For low frequencies, it behaves similarly to a reflector dish, directing sounds toward the ear canal. For high frequencies, however, its value is more sophisticatedly reckoned. While some of the sounds that enter the ear travel directly to the canal, others reflect off the contours of the pinna first: these enter the ear canal at a very slight delay. Such a delay translates into phase cancellation, where the frequency component whose wave period is twice the delay period is virtually eliminated. Neighboring frequencies are dropped significantly. This is known as the pinna notch, where the pinna creates a notch filtering effect.
# Anatomy
The diagram shows the shape and location of these components:
- Anthelix (antihelix) forms a 'Y' shape where the upper parts are:
Superior crux (to the left of the fossa triangularis in the diagram)
Inferior crux (to the right of the fossa triangularis in the diagram)
- Superior crux (to the left of the fossa triangularis in the diagram)
- Inferior crux (to the right of the fossa triangularis in the diagram)
- Antitragus is below the tragus
- Auricular sulcus is the depression behind the ear next to the head
- Concha is the hollow next to the ear canal
- Conchal angle is the angle that the back of the concha makes with the side of the head
- Crus of the helix is just above the tragus
- Cymba conchae is the narrowest end of the concha
- External auditory meatus is the opening to the ear canal
- Fossa triangularis is the depression in the fork of the anthelix
- Helix is the folded over outside edge of the ear
- Incisura anterior (auris) is between the tragus and the antitragus
- Lobe (lobule) - attached or free according to a classic single-gene dominance relationship
- Scapha
- Tragus
# Embryology
The developing Pinna is first noticeable around the sixth week of gestation in the human foetus, developing from six rounded protuberances (the six hillocks of Hiss) which are derived from the first and second branchial arches.
These hillocks develop into the folds of the pinna and gradually shift upwards and backwards to their final position on the head. En-route accessory auricles (also known as preauricular tags - see below) may be left behind.
The first three Hillocks are dervied from the 1st branchial arch and form the tragus, crus of the helix and helix respectively. Cutaneous sensation to these areas is via the trigeminal nerve, the attendant nerve of the 1st branchial arch.
The final three Hillockes are derived from the 2nd branchial arch and form the antihelix, antitragus and lobule respectively. These portions of the ear are supplied by the cervical plexus and a small portion by the facial nerve. This explains why vesicles are classically seen on the Pinna in Herpes infection of the facial nerve ( Ramsay-Hunt Syndrome)
# Abnormalities
There are various visible ear abnormalities:
- Bat ear (also known as wingnut ear) — an ear that protrudes
- Cryptotia (hidden ear) — upper auricular sulcus not visible
- Cup deformity — helical rim is compressed
- Darwinian tubercle (auricular tubercle) — a projection from the helical rim
- Lop ear — the top of the helical rim folded over
- Macrotia (also known as big ears, or hypertrophy of the ears)
- Microtia (small or partially developed ears)
- Preauricular sinus (small holes usually visible from birth at the front of the ears where the pinna joins the head)
- Accessory Auricles (small pieces of skin at the front of the ears where the pinna joins the head, vestigial remnants of the developing ears migration to it's final position)
- Rim kinks — a kink of the helical rim
- Selhurst's handle (also known as cup handle) — an ear that can be 50% larger than normal.
- Stahl’s bar (also known as Spock ear) — third crus (in between the superior crux and inferior crux) making the top of the ear pointed
- Zaheer's ear — having a deformed anti-tragus, which appears as a bump, as opposed to a protrusion, which would normally allow the snug insertion of earbud headphones
- Congenital Pit of the Cymba Conchae — This is a blind cavity that does not communicate with the external auditory canal. It occasionally fills with sebaceous material, desquamated skin or debris and requires cleaning or "scooping" with a wax curette [1].
# Additional images
- External and middle ear, opened from the front. Right side.
- Left ear | https://www.wikidoc.org/index.php/Auricle | |
5847d9b7d1ef87e423634d9d322b79e3fe6f371b | wikidoc | Azide | Azide
Azide is the anion with the formula N3−. It is the conjugate base of hydrazoic acid. Azide is also a functional group in organic chemistry, RN3. N3− is a linear anion that is isoelectronic with CO2 and N2O. Per valence bond theory, azide can be described by several resonance structures, an important one being N−=N+=N−.
# Inorganic azides
Azide forms both covalent and ionic compounds with metals. Sodium azide, NaN3, is a salt that is widely used as the propellant in airbags. Covalent azides are numerous, an example being Cl2. A metal-organic azide is trimethylsilylazide, which is sometimes used as an anhydrous source of N3−.
# Azides in biochemistry
The azide anion is toxic, inhibiting the function of cytochrome c oxidase by binding irreversibly to the heme cofactor, in a process similar to that of cyanide. Azide salts are also used in studies of mutagenesis.
# Organic azides
Organic azides engage in useful organic reactions. The terminal nitrogen is mildly nucleophilic. Azides easily extrude diatomic nitrogen, a tendency that is exploited in many reactions such as the Staudinger Ligation or the Curtius rearrangement or for example in the synthesis of γ-imino-β-enamino esters .
In the azide alkyne Huisgen cycloaddition, organic azides react as 1,3-dipoles. Examples of organic azides are the chemical reagent phenyl azide and the antiviral drug zidovudine (AZT).
Another azide regular is tosyl azide here in reaction with norbornadiene in a nitrogen insertion reaction :
# Dutt-Wormall reaction
A classic method for the synthesis of azides is the Dutt-Wormall reaction in which a diazonium salt reacts with a sulfonamide first to a diazoaminosulfinate and then on hydrolysis the azide and a sulfinic acid .
# Safety
- Sodium azide is toxic (LD50 oral (rats) = 27 mg/kg) and can be absorbed through the skin.
- Heavy metal azides, such as lead azide are very unstable primary high explosives detonable when heated or shaken.
- Sodium azide decomposes explosively upon heating to above 275 °C.
- Sodium azide reacts vigorously with CS2, bromine, nitric acid, dimethyl sulfate, and a series of heavy metals, including copper and lead.
- In reaction with water or Brønsted acids the highly toxic and explosive hydrogen azide is released.
- It has been reported that sodium azide and polymer-bound azide reagents react with dichloromethane and chloroform to form di- and triazidomethane resp., which are both unstable in high concentrations in solution. Various devastating explosions were reported while reaction mixtures were being concentrated on a rotary evaporator. The hazards of diazidomethane (and triazidomethane) have been well documented by A. Hassner et al. .
- Heavy-metal azides that are highly explosive under pressure or shock are formed when solutions of sodium azide or HN3 vapors come into contact with heavy metals or their salts. Heavy-metal azides can accumulate under certain circumstances, for example, in metal pipelines and on the metal components of diverse equipment (rotary evaporators, freezedrying equipment, cooling traps, water baths, waste pipes), and thus lead to violent explosions. Some organic and other covalent azides are classified as highly explosive and toxic (inorganic azides as neurotoxins; azide ions as cytochrome c oxidase (COX) inhibitors).
- Solid iodoazide is explosive and should not be prepared in the absence of solvent.. | Azide
Azide is the anion with the formula N3−. It is the conjugate base of hydrazoic acid. Azide is also a functional group in organic chemistry, RN3[1]. N3− is a linear anion that is isoelectronic with CO2 and N2O. Per valence bond theory, azide can be described by several resonance structures, an important one being N−=N+=N−.
# Inorganic azides
Azide forms both covalent and ionic compounds with metals. Sodium azide, NaN3, is a salt that is widely used as the propellant in airbags. Covalent azides are numerous,[2] an example being [Co(NH3)5N3]Cl2. A metal-organic azide is trimethylsilylazide, which is sometimes used as an anhydrous source of N3−.
# Azides in biochemistry
The azide anion is toxic, inhibiting the function of cytochrome c oxidase by binding irreversibly to the heme cofactor, in a process similar to that of cyanide. Azide salts are also used in studies of mutagenesis.
# Organic azides
Organic azides engage in useful organic reactions. The terminal nitrogen is mildly nucleophilic. Azides easily extrude diatomic nitrogen, a tendency that is exploited in many reactions such as the Staudinger Ligation or the Curtius rearrangement or for example in the synthesis of γ-imino-β-enamino esters [3] [4].
In the azide alkyne Huisgen cycloaddition, organic azides react as 1,3-dipoles. Examples of organic azides are the chemical reagent phenyl azide and the antiviral drug zidovudine (AZT).
Another azide regular is tosyl azide here in reaction with norbornadiene in a nitrogen insertion reaction [5]:
# Dutt-Wormall reaction
A classic method for the synthesis of azides is the Dutt-Wormall reaction [6] in which a diazonium salt reacts with a sulfonamide first to a diazoaminosulfinate and then on hydrolysis the azide and a sulfinic acid [7].
# Safety
- Sodium azide is toxic (LD50 oral (rats) = 27 mg/kg) and can be absorbed through the skin.
- Heavy metal azides, such as lead azide are very unstable primary high explosives detonable when heated or shaken.
- Sodium azide decomposes explosively upon heating to above 275 °C.
- Sodium azide reacts vigorously with CS2, bromine, nitric acid, dimethyl sulfate, and a series of heavy metals, including copper and lead.
- In reaction with water or Brønsted acids the highly toxic and explosive hydrogen azide is released.
- It has been reported that sodium azide and polymer-bound azide reagents react with dichloromethane and chloroform to form di- and triazidomethane resp., which are both unstable in high concentrations in solution. Various devastating explosions were reported while reaction mixtures were being concentrated on a rotary evaporator. The hazards of diazidomethane (and triazidomethane) have been well documented by A. Hassner et al. [8].
- Heavy-metal azides that are highly explosive under pressure or shock are formed when solutions of sodium azide or HN3 vapors come into contact with heavy metals or their salts. Heavy-metal azides can accumulate under certain circumstances, for example, in metal pipelines and on the metal components of diverse equipment (rotary evaporators, freezedrying equipment, cooling traps, water baths, waste pipes), and thus lead to violent explosions. Some organic and other covalent azides are classified as highly explosive and toxic (inorganic azides as neurotoxins; azide ions as cytochrome c oxidase (COX) inhibitors).
- Solid iodoazide is explosive and should not be prepared in the absence of solvent.[9].
# External links
- http://azides.org
- Synthesis of organic azides, recent methods
- Synthesizing, Purifying, and Handling Organic Azides
- Preparation of Polyfunctional Acyl Azides
- Synthesis and Reduction of Azides | https://www.wikidoc.org/index.php/Azide | |
239383f21e071050e0d65c42e3fc8d69fb4c0f8b | wikidoc | BAALC | BAALC
BAALC is a gene that codes for the: brain and acute leukemia cytoplasmic protein. The official symbol (BAALC) and official name (brain and acute leukemia cytoplasmic) is maintained by the HGNC. The function of BAALC is not fully understood yet but has been suggested to have synaptic roles involving the post synaptic lipid raft. Lipid rafts are microdomains that are enriched with cholesterol and sphingolipids, lipid raft functions include membrane trafficking, signal processing, and regulation of the actin cytoskeleton. The postsynpatic lipid raft possesses many proteins and is one of the major sites for signal processing and postsynaptic density (PSD). Along with its involvement in the post synaptic lipid rafts, BAALC expression has been associated with Acute Lymphoblastic Leukemia and Acute Myeloid Leukemia.
# Genetics
BAALC gene is located on the long arm (q) of chromosome 8 at position 22.3 (8q22.3). The human BAALC gene contains eight exons, spans 89 613 bases of genomic DNA, and the transcript contains 180 amino acids.
The BAALC gene is highly conserved in mammals, domestic pigs, mice and rats. But BAALC is not seen in lower organisms such as: Drosophila. melanogaster, Saccharomyces. cerevisiae, and Caenorhabditis. elegans.
BAALC and its protein are expressed highly in neural tissues such as the Central Nervous System (CNS) and the Spinal Cord, and less expressed in neuroectodermal-derived tissues like the adrenal glands. The BAALC protein is not expressed in peripheral blood leukocytes (PBL), lymph nodes, or nonneural tissues. BAALC expression has only been found in Bone Marrow (BM) when expressed from CD34+ progenitor cells, besides this BAALC expression has not been visualized. The expression of BAALC from the CD34+ progenitor cells suggest the gene has neuroectodermal and hematopoietic cell functions. BAALC expression is higher in neuroectodermal-derived tissues such as the frontal part of the brain, more specifically in the hippocampus, and neocortex.
The BAALC gene has eight different transcripts that result into six different protein isoforms. Isoforms that carry the exon number two do not express protein and it is believed that the termination in exon two results in an unstable protein after translation. The isoforms 1-6-8 and 1-8 are neuroectodermal isoforms and these are highly conserved in the above-mentioned mammals.
# Function
The BAALC gene initially was discovered in the neuroderm of both the human and the mouse. The function of BAALC protein is not understood very well, but it is predicted to be associated with the cytoskeleton network. When expressed in Bone Marrow CD34+ progenitor cells, BAALC has neuroectodermal and hematopoietic cell functions. Differentiation failure caused by cell shape, motility and adhesion in association between cells are all possible outcomes due to the little known effects and unlear mechanism sites of the BAALC genes. The role of the BAALC gene causing leukemia in immature acute leukemic cells has been found by knocking out the function of BAALC gene using hairpin (stem loop) RNA in a human leukemia cell line KG1a. The result of knocking out BAALC expression is a decrease in uncontrolled cell growth and an increase in programmed cell death. The BAALC protein isoform 1-6-8, has been found to interact and associate with the CAMKII alpha subunit and not with the beta subunit. The interaction with the CAMKII alpha subunit is in the CAMKII protein's regulatory region and near the autophosphorylation site, this suggested a regulatory function of the 1-6-8 isoform on the alpha subunit. BAALC 1-6-8 isoform also gets targeted to post synaptic lipid rafts, which are thought to have functions involved in: signal processing, membrane trafficking, and regulation of the actin cytoskeleton. BAALC may play a role in the regulation of the CAMKII protein through interactions with the alpha subunit, no interactions have been found with the beta subunit of this protein. Evidence has shown the BAALC protein to be an intracellular protein with cytoskeleton network roles, these roles include regulation of the actin cytoskeleton which is an associated role of postsynaptic lipid rafts.
# Clinical Significance
In studies it has been found that overexpression of BAALC is seen in 28% of people with AML and 65% of people with ALL. BAALC is ruled out as a marker for neoplasia because it is not expressed in other cancer cells. BAALC is seen in acute leukemia in immature myoblasts and early progenitor cells, but is excluded from mature hematopoietic cells. It has been found in studies that acute myeloid leukemia patients who over expressed BAALC (BAALC Positive) had a median of approximately 5 months of event free survival, but those who were BAALC negative had a median of around 15 months. Research has found when BAALC is combined with the oncogene Hoxa9, BAALC blocks myeloid differentiation. This blocking induces leukemogenesis. BAALC over-expression is associated with IDH1 and IDH2 wild type in Chinese cytogenetically normal acute myeloid leukemia patients. The results found by Zhou et al. are different than that found by Weber et al. where no difference in mutations in IDH1 and IDH2 where seen depending on expression of BAALC. IGFBP7 is another gene involved in leukemia, this was found conducting gene expression profiles (GEP) with BAALC. This gene has BAALC characteristics and, unlike BAALC, may have a role in drug resistance and the mechanism of leukemogenesis. It has been found that treatment for some acute leukemias failed due to BAALC and this suggests BAALC to be a potential surrogate marker. The use of BAALC expression in acute leukemia prognosis is unclear and being studied.Prognosis of patients with AML and BAALC over-expression has been found to be poor or worse than poor. Over-expression of the BAALC gene and considerable accumulation of the gene production has been found to have caused drug resistance in patients.
# Expression in Cancers
Overexpression of the BAALC gene is seen in Acute Myeloid Leukemia (AML) and Acute Lymphoblastic Leukemia (ALL). It has been found that BAALC can cause the start of Leukemia (leukemogenesis) by stopping the differentiation of myeloid. Silencing BAALC lowers the amount of proliferation and increased cell death (apoptosis) in leukemic cell lines KG1a It has also been found with the over-expression of the BAALC genes to cause low levels of complete remission in cancer patients, and low amount of overall survival in patients.
# Structure
The human BAALC gene contains eight exons, spans 89 613 bases of genomic DNA, and the transcript contains 180 amino acids. This gene codes for eight different transcripts that are translated into six different protein isoforms. Isoforms containing exon number two (1-2-6-8 and 1-2-5-6-8) do not code protein and so exon two contains a termination codon. The isoforms 1-6-8 and 1-8 are neuroectodermal isoforms and these are highly conserved in mammals.
BAALC protein isoform 1-6-8 is modified by myristoylation an palmitoylation at the N-terminal. These modifications occur on the Glycine 2 and Cysteine 3 amino acids of the protein. These modifications are used for targeting the protein to the lipid rafts. Little phosphorylation of the BAALC isoform 1-6-8 by the CAMK2A protein has been found as well.
# Interactions
CAMK2A | BAALC
BAALC is a gene that codes for the: brain and acute leukemia cytoplasmic protein.[1] The official symbol (BAALC) and official name (brain and acute leukemia cytoplasmic) is maintained by the HGNC.[2] The function of BAALC is not fully understood yet but has been suggested to have synaptic roles involving the post synaptic lipid raft.[3] Lipid rafts are microdomains that are enriched with cholesterol and sphingolipids, lipid raft functions include membrane trafficking, signal processing, and regulation of the actin cytoskeleton.[3] The postsynpatic lipid raft possesses many proteins and is one of the major sites for signal processing and postsynaptic density (PSD).[3] Along with its involvement in the post synaptic lipid rafts, BAALC expression has been associated with Acute Lymphoblastic Leukemia and Acute Myeloid Leukemia.[1]
# Genetics
BAALC gene is located on the long arm (q) of chromosome 8 at position 22.3 (8q22.3).[4] The human BAALC gene contains eight exons, spans 89 613 bases of genomic DNA, and the transcript contains 180 amino acids.[4][5]
The BAALC gene is highly conserved in mammals, domestic pigs, mice and rats.[1] But BAALC is not seen in lower organisms such as: Drosophila. melanogaster, Saccharomyces. cerevisiae, and Caenorhabditis. elegans.[1]
BAALC and its protein are expressed highly in neural tissues such as the Central Nervous System (CNS) and the Spinal Cord, and less expressed in neuroectodermal-derived tissues like the adrenal glands.[1] The BAALC protein is not expressed in peripheral blood leukocytes (PBL), lymph nodes, or nonneural tissues.[1][4] BAALC expression has only been found in Bone Marrow (BM) when expressed from CD34+ progenitor cells, besides this BAALC expression has not been visualized.[1] The expression of BAALC from the CD34+ progenitor cells suggest the gene has neuroectodermal and hematopoietic cell functions.[6][1][7] BAALC expression is higher in neuroectodermal-derived tissues such as the frontal part of the brain, more specifically in the hippocampus, and neocortex.[3]
The BAALC gene has eight different transcripts that result into six different protein isoforms.[8] Isoforms that carry the exon number two do not express protein and it is believed that the termination in exon two results in an unstable protein after translation.[1] The isoforms 1-6-8 and 1-8 are neuroectodermal isoforms and these are highly conserved in the above-mentioned mammals.[1]
# Function
The BAALC gene initially was discovered in the neuroderm of both the human and the mouse.[1] The function of BAALC protein is not understood very well, but it is predicted to be associated with the cytoskeleton network.[1] When expressed in Bone Marrow CD34+ progenitor cells, BAALC has neuroectodermal and hematopoietic cell functions.[1] Differentiation failure caused by cell shape, motility and adhesion in association between cells are all possible outcomes due to the little known effects and unlear mechanism sites of the BAALC genes.[7] The role of the BAALC gene causing leukemia in immature acute leukemic cells has been found by knocking out the function of BAALC gene using hairpin (stem loop) RNA in a human leukemia cell line KG1a.[9] The result of knocking out BAALC expression is a decrease in uncontrolled cell growth and an increase in programmed cell death.[9][7] The BAALC protein isoform 1-6-8, has been found to interact and associate with the CAMKII alpha subunit and not with the beta subunit.[3] The interaction with the CAMKII alpha subunit is in the CAMKII protein's regulatory region and near the autophosphorylation site, this suggested a regulatory function of the 1-6-8 isoform on the alpha subunit.[3] BAALC 1-6-8 isoform also gets targeted to post synaptic lipid rafts, which are thought to have functions involved in: signal processing, membrane trafficking, and regulation of the actin cytoskeleton.[3] BAALC may play a role in the regulation of the CAMKII protein through interactions with the alpha subunit, no interactions have been found with the beta subunit of this protein.[3] Evidence has shown the BAALC protein to be an intracellular protein with cytoskeleton network roles, these roles include regulation of the actin cytoskeleton which is an associated role of postsynaptic lipid rafts.[1][3]
# Clinical Significance
In studies it has been found that overexpression of BAALC is seen in 28% of people with AML and 65% of people with ALL.[1] BAALC is ruled out as a marker for neoplasia because it is not expressed in other cancer cells.[1] BAALC is seen in acute leukemia in immature myoblasts and early progenitor cells, but is excluded from mature hematopoietic cells.[9][1] It has been found in studies that acute myeloid leukemia patients who over expressed BAALC (BAALC Positive) had a median of approximately 5 months of event free survival, but those who were BAALC negative had a median of around 15 months.[1] Research has found when BAALC is combined with the oncogene Hoxa9, BAALC blocks myeloid differentiation.[10] This blocking induces leukemogenesis. BAALC over-expression is associated with IDH1 and IDH2 wild type in Chinese cytogenetically normal acute myeloid leukemia patients.[10] The results found by Zhou et al. are different than that found by Weber et al. where no difference in mutations in IDH1 and IDH2 where seen depending on expression of BAALC.[9] IGFBP7 is another gene involved in leukemia, this was found conducting gene expression profiles (GEP) with BAALC.[10] This gene has BAALC characteristics and, unlike BAALC, may have a role in drug resistance and the mechanism of leukemogenesis.[10] It has been found that treatment for some acute leukemias failed due to BAALC and this suggests BAALC to be a potential surrogate marker.[10] The use of BAALC expression in acute leukemia prognosis is unclear and being studied.[7][6]Prognosis of patients with AML and BAALC over-expression has been found to be poor or worse than poor.[7] Over-expression of the BAALC gene and considerable accumulation of the gene production has been found to have caused drug resistance in patients.[7]
# Expression in Cancers
Overexpression of the BAALC gene is seen in Acute Myeloid Leukemia (AML) and Acute Lymphoblastic Leukemia (ALL).[10][11] It has been found that BAALC can cause the start of Leukemia (leukemogenesis) by stopping the differentiation of myeloid.[12] Silencing BAALC lowers the amount of proliferation and increased cell death (apoptosis) in leukemic cell lines KG1a[9] It has also been found with the over-expression of the BAALC genes to cause low levels of complete remission in cancer patients, and low amount of overall survival in patients.[7]
# Structure
The human BAALC gene contains eight exons, spans 89 613 bases of genomic DNA, and the transcript contains 180 amino acids.[4][5] This gene codes for eight different transcripts that are translated into six different protein isoforms.[1][8] Isoforms containing exon number two (1-2-6-8 and 1-2-5-6-8) do not code protein and so exon two contains a termination codon.[1] The isoforms 1-6-8 and 1-8 are neuroectodermal isoforms and these are highly conserved in mammals.[1]
BAALC protein isoform 1-6-8 is modified by myristoylation an palmitoylation at the N-terminal.[3] These modifications occur on the Glycine 2 and Cysteine 3 amino acids of the protein.[3] These modifications are used for targeting the protein to the lipid rafts.[3] Little phosphorylation of the BAALC isoform 1-6-8 by the CAMK2A protein has been found as well.[3]
# Interactions
CAMK2A[5][4] | https://www.wikidoc.org/index.php/BAALC | |
eecd212f72a887b26e145f8718d7ddbaefbecd01 | wikidoc | BACE1 | BACE1
β-Secretase — also called BACE1 (β-site of APP cleaving enzyme) or memapsin-2 — is an aspartic-acid protease important in the pathogenesis of Alzheimer's disease, and in the formation of myelin sheaths in peripheral nerve cells. The transmembrane protein, contains two active site aspartate residues in its extracellular protein domain and may function as a dimer.
# Function in Alzheimer's
Generation of the 40 or 42 amino acid-long amyloid-β peptides that aggregate in the brain of Alzheimer's patients requires two sequential cleavages of the amyloid precursor protein (APP). Extracellular cleavage of APP by BACE releases a soluble extracellular fragment and is followed by APP cleavage within its transmembrane domain by γ-secretase. The second cleavage releases the intracellular domain of APP and amyloid-β. Since α-secretase cleaves APP closer to the cell membrane than BACE does, it removes a fragment of the amyloid-β peptide. Initial cleavage of APP by α-secretase rather than BACE prevents eventual generation of amyloid-β.
Unlike APP and the presenilin proteins important in γ-secretase, no known mutations in the gene encoding BACE cause the early-onset, familial Alzheimer's disease. However, levels of this enzyme have been shown to be elevated in Alzheimer's. The physiological purpose of BACE's cleavage of APP and other transmembrane proteins is unknown. BACE2 is a close homolog of BACE1.
# BACE inhibitors
Drugs to block this enzyme (BACE inhibitors) in theory would prevent the build up of beta-amyloid and may help slow or stop the disease. Several companies are in the early stages of development and testing of this new potential class of treatment. | BACE1
β-Secretase — also called BACE1 (β-site of APP cleaving enzyme) or memapsin-2 — is an aspartic-acid protease important in the pathogenesis of Alzheimer's disease, and in the formation of myelin sheaths in peripheral nerve cells.[1] The transmembrane protein, contains two active site aspartate residues in its extracellular protein domain and may function as a dimer.
# Function in Alzheimer's
Generation of the 40 or 42 amino acid-long amyloid-β peptides that aggregate in the brain of Alzheimer's patients requires two sequential cleavages of the amyloid precursor protein (APP). Extracellular cleavage of APP by BACE releases a soluble extracellular fragment and is followed by APP cleavage within its transmembrane domain by γ-secretase. The second cleavage releases the intracellular domain of APP and amyloid-β. Since α-secretase cleaves APP closer to the cell membrane than BACE does, it removes a fragment of the amyloid-β peptide. Initial cleavage of APP by α-secretase rather than BACE prevents eventual generation of amyloid-β.
Unlike APP and the presenilin proteins important in γ-secretase, no known mutations in the gene encoding BACE cause the early-onset, familial Alzheimer's disease. However, levels of this enzyme have been shown to be elevated in Alzheimer's. The physiological purpose of BACE's cleavage of APP and other transmembrane proteins is unknown. BACE2 is a close homolog of BACE1.
# BACE inhibitors
Drugs to block this enzyme (BACE inhibitors) in theory would prevent the build up of beta-amyloid and may help slow or stop the disease. Several companies are in the early stages of development and testing of this new potential class of treatment.[2][3] | https://www.wikidoc.org/index.php/BACE | |
86ebd73d21480143e77f81c74b202e58461f3ea0 | wikidoc | BACH2 | BACH2
Transcription regulator protein BACH2 (broad complex-tramtrack-bric a brac and Cap'n'collar homology 2) is a protein that in humans is encoded by the BACH2 gene. It contains a BTB/POZ domain at its N-terminus which forms a disulphide-linked dimer and a bZip_Maf domain at the C-terminus.
# Disease associations
Single nucleotide variants in BACH2 have been linked to a number of autoimmune diseases in humans. Mendelian BACH2-related immunodeficiency and autoimmunity (BRIDA) syndrome in humans is caused by haploinsufficiency of this transcription factor resulting from germline mutations.
# Model organisms
Model organisms have been used in the study of BACH2 function. A conditional knockout mouse line called Bach2tm1a(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 - in-depth bone and cartilage phenotyping | BACH2
Transcription regulator protein BACH2 (broad complex-tramtrack-bric a brac and Cap'n'collar homology 2) is a protein that in humans is encoded by the BACH2 gene.[1][2][3] It contains a BTB/POZ domain at its N-terminus which forms a disulphide-linked dimer [4] and a bZip_Maf domain at the C-terminus.
# Disease associations
Single nucleotide variants in BACH2 have been linked to a number of autoimmune diseases in humans.[5] Mendelian BACH2-related immunodeficiency and autoimmunity (BRIDA) syndrome in humans is caused by haploinsufficiency of this transcription factor resulting from germline mutations.[6]
# Model organisms
Model organisms have been used in the study of BACH2 function. A conditional knockout mouse line called Bach2tm1a(EUCOMM)Wtsi was generated at the Wellcome Trust Sanger Institute.[7] Male and female animals underwent a standardized phenotypic screen[8] to determine the effects of deletion.[9][10][11][12] Additional screens performed: - In-depth immunological phenotyping[13] - in-depth bone and cartilage phenotyping[14] | https://www.wikidoc.org/index.php/BACH2 | |
86a2cda3dd579a454ddc13a9399bb1e98a859386 | wikidoc | BARD1 | BARD1
BRCA1-associated RING domain protein 1 is a protein that in humans is encoded by the BARD1 gene. The human BARD1 protein is 777 amino acids long and contains a RING finger domain (residues 46-90), four ankyrin repeats (residues 420-555), and two tandem BRCT domains (residues 568-777).
# Function
Most, if not all, BRCA1 heterodimerizes with BARD1 in vivo. BARD1 and BRCA1 form a heterodimer via their N-terminal RING finger domains. The BARD1-BRCA1 interaction is observed in vivo and in vitro and is essential for BRCA1 stability. BARD1 shares homology with the two most conserved regions of BRCA1: the N-terminal RING motif and the C-terminal BRCT domain. The RING motif is a cysteine-rich sequence found in a variety of proteins that regulate cell growth, including the products of tumor suppressor genes and dominant protooncogenes, and developmentally important genes such as the polycomb group of genes. The BARD1 protein also contains three tandem ankyrin repeats.
The BARD1/BRCA1 interaction is disrupted by tumorigenic amino acid substitutions in BRCA1, implying that the formation of a stable complex between these proteins may be an essential aspect of BRCA1 tumor suppression. BARD1 may be the target of oncogenic mutations in breast or ovarian cancer. Mutations in the BARD1 protein that affect its structure appear in many breast, ovarian, and uterine cancers, suggesting the mutations disable BARD1's tumor suppressor function. Three missense mutations, each affecting BARD1's BRCT domain, are known to be implicated in cancers: C645R is associated with breast and ovarian cancers, V695L is associated with breast cancer, and S761N is associated with breast and uterine cancers. BARD1 expression is upregulated by genotoxic stress and involved in apoptosis through binding and stabilizing p53 independently of BRCA1.
BARD1 is vital in the rapid relocation of BRCA1 to DNA damage sites. BARD1 tandem BRCA1 C-terminus (BRCT) motifs fold into a binding pocket with a key lysine residue (K619), and bind to poly(ADP-ribose) (PAR), which targets the BRCA1/BARD1 heterodimer to damaged DNA sites. Double stranded breaks (DSB) in DNA trigger poly(ADPribose) polymerase 1 (PARP1) to catalyze the formation of poly(ADPribose) (PAR) so that PAR can then bind to an array of DNA response proteins, including the BRCA1/BARD1 heterodimer, and target them to DNA damage sites. When the BRCA1/BARD1 heterodimer is transported to the damaged DNA site, it acts as an E3 ubiquitin ligase. The BRCA1/BARD1 heterodimer ubiquitinates RNA polymerase II, preventing the transcription of the damaged DNA, and restoring genetic stability.
# Interactions
BARD1 has been shown to interact with:
- AURKB,
- BCL3,
- BRCA1,
- BRCA2,
- BRCC3,
- BRE,
- CSTF1,
- CSTF2,
- EWSR1,
- FANCD2,
- H2AFX,
- NPM1,
- P53,
- RAD51,
- TACC1, and
- UBE2D1.
# Implication in Cancer Treatments
If a cancer cell's capacity to repair DNA damage were incapacitated, cancer treatments would be more effective. Inhibiting cancer cells' BRCA1/BARD1 heterodimer from relocating to DNA damage sites would induce tumor cell death rather than repair. One inhibition possibility is the BARD1 BRCT key lysine residue (K619). Inhibiting this lysine residue's ability to bind poly(ADP-ribose) would prevent the BRCA1/BARD1 heterodimer from localizing to DNA damage sites and subsequently prevent DNA damage repair. This would make cancer therapies such as chemotherapy and radiation vastly more effective. | BARD1
BRCA1-associated RING domain protein 1 is a protein that in humans is encoded by the BARD1 gene.[1][2][3] The human BARD1 protein is 777 amino acids long and contains a RING finger domain (residues 46-90), four ankyrin repeats (residues 420-555), and two tandem BRCT domains (residues 568-777).[4]
# Function
Most, if not all, BRCA1 heterodimerizes with BARD1 in vivo.[5] BARD1 and BRCA1 form a heterodimer via their N-terminal RING finger domains. The BARD1-BRCA1 interaction is observed in vivo and in vitro and is essential for BRCA1 stability. BARD1 shares homology with the two most conserved regions of BRCA1: the N-terminal RING motif and the C-terminal BRCT domain. The RING motif is a cysteine-rich sequence found in a variety of proteins that regulate cell growth, including the products of tumor suppressor genes and dominant protooncogenes, and developmentally important genes such as the polycomb group of genes. The BARD1 protein also contains three tandem ankyrin repeats.[6][7]
The BARD1/BRCA1 interaction is disrupted by tumorigenic amino acid substitutions in BRCA1, implying that the formation of a stable complex between these proteins may be an essential aspect of BRCA1 tumor suppression. BARD1 may be the target of oncogenic mutations in breast or ovarian cancer.[6] Mutations in the BARD1 protein that affect its structure appear in many breast, ovarian, and uterine cancers, suggesting the mutations disable BARD1's tumor suppressor function.[4] Three missense mutations, each affecting BARD1's BRCT domain, are known to be implicated in cancers: C645R is associated with breast and ovarian cancers, V695L is associated with breast cancer, and S761N is associated with breast and uterine cancers.[4] BARD1 expression is upregulated by genotoxic stress and involved in apoptosis through binding and stabilizing p53 independently of BRCA1.[8]
BARD1 is vital in the rapid relocation of BRCA1 to DNA damage sites.[9] BARD1 tandem BRCA1 C-terminus (BRCT) motifs fold into a binding pocket with a key lysine residue (K619), and bind to poly(ADP-ribose) (PAR), which targets the BRCA1/BARD1 heterodimer to damaged DNA sites.[9] Double stranded breaks (DSB) in DNA trigger poly(ADPribose) polymerase 1 (PARP1) to catalyze the formation of poly(ADPribose) (PAR) so that PAR can then bind to an array of DNA response proteins, including the BRCA1/BARD1 heterodimer, and target them to DNA damage sites.[10] When the BRCA1/BARD1 heterodimer is transported to the damaged DNA site, it acts as an E3 ubiquitin ligase.[5] The BRCA1/BARD1 heterodimer ubiquitinates RNA polymerase II, preventing the transcription of the damaged DNA, and restoring genetic stability.[11]
# Interactions
BARD1 has been shown to interact with:
- AURKB,[12]
- BCL3,[13]
- BRCA1,[1][3][12][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41][42]
- BRCA2,[12][14]
- BRCC3,[14]
- BRE,[14]
- CSTF1,[22][23]
- CSTF2,[22][23]
- EWSR1,[43]
- FANCD2,[20]
- H2AFX,[15][17]
- NPM1,[18]
- P53,[14]
- RAD51,[14]
- TACC1,[12] and
- UBE2D1.[14][15][16][17][18][19][20][21]
# Implication in Cancer Treatments
If a cancer cell's capacity to repair DNA damage were incapacitated, cancer treatments would be more effective. Inhibiting cancer cells' BRCA1/BARD1 heterodimer from relocating to DNA damage sites would induce tumor cell death rather than repair. One inhibition possibility is the BARD1 BRCT key lysine residue (K619). Inhibiting this lysine residue's ability to bind poly(ADP-ribose) would prevent the BRCA1/BARD1 heterodimer from localizing to DNA damage sites and subsequently prevent DNA damage repair. This would make cancer therapies such as chemotherapy and radiation vastly more effective.[44] | https://www.wikidoc.org/index.php/BARD1 | |
92bb86647c887dd52cff8c32be1d864198d57416 | wikidoc | BAZ1A | BAZ1A
Bromodomain adjacent to zinc finger domain protein 1A is a protein that in humans is encoded by the BAZ1A gene.
# Structure
The protein encoded by this gene belongs to a family of proteins which includes BAZ1B, BAZ2A, and BAZ2B. All family members contain the following domains and structural motifs:
- N-terminus – PHD finger (C4HC3 zinc finger)
- WAKZ motif
- LH (leucine-rich helical domain) motif
- C-terminus – bromodomain
# Function
BAZ1A along with SMARCA5, POLE3, and CHRAC1 comprise the WCRF/CHRAC ATP-dependent chromatin-remodeling complex.
The purified CHRAC complex can mobilize nucleosomes into a regularly spaced nucleosomal array, and the spacing activity is ATP-dependent. Furthermore, the BAZ1A-SMARCA5 complex enables DNA replication through highly condensed regions of chromatin.
# Interactions
BAZ1A has been shown to interact with SMARCA5 and SATB1. | BAZ1A
Bromodomain adjacent to zinc finger domain protein 1A is a protein that in humans is encoded by the BAZ1A gene.[1][2]
# Structure
The protein encoded by this gene belongs to a family of proteins which includes BAZ1B, BAZ2A, and BAZ2B. All family members contain the following domains and structural motifs:[1]
- N-terminus – PHD finger (C4HC3 zinc finger)
- WAKZ motif
- LH (leucine-rich helical domain) motif
- C-terminus – bromodomain
# Function
BAZ1A along with SMARCA5, POLE3, and CHRAC1 comprise the WCRF/CHRAC ATP-dependent chromatin-remodeling complex.[3][4]
The purified CHRAC complex can mobilize nucleosomes into a regularly spaced nucleosomal array, and the spacing activity is ATP-dependent.[4] Furthermore, the BAZ1A-SMARCA5 complex enables DNA replication through highly condensed regions of chromatin.[5]
# Interactions
BAZ1A has been shown to interact with SMARCA5[3][4][6][7][8] and SATB1.[7] | https://www.wikidoc.org/index.php/BAZ1A | |
6ecf30c2927337b5b00e1ba054939cf5025a6c33 | wikidoc | BAZ1B | BAZ1B
Tyrosine-protein kinase BAZ1B is an enzyme that in humans is encoded by the BAZ1B gene.
# Function
This gene encodes a member of the bromodomain protein family. The bromodomain is a structural motif characteristic of proteins involved in chromatin-dependent regulation of transcription. This gene is deleted in Williams-Beuren syndrome, a developmental disorder caused by deletion of multiple genes at 7q11.23.
# Animal models
Model organisms have been used in the study of BAZ1B function. A conditional knockout mouse line, called Baz1btm2a(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.
Six significant phenotypes were reported:
- Fewer homozygous mutant mice survived to weaning than expected.
- Mutant mice had decreased body weights compared to wildtype control mice.
- Mutant mice showed increased activity, VO2 and energy expenditure, determined by indirect calorimetry.
- Radiography found teeth abnormalities.
- Dual-energy X-ray absorptiometry (DEXA) showed mutant female mice had a decrease in bone mineral density and content.
- Male heterozygous mice had higher bacterial counts after Salmonella infection.
# Interactions
BAZ1B has been shown to interact with:
- CHAF1A,
- SMARCB1,
- SMARCC1,
- SMARCC2,
- SUPT16H
- TOP2B, and
- VDR. | BAZ1B
Tyrosine-protein kinase BAZ1B is an enzyme that in humans is encoded by the BAZ1B gene.[1][2][3]
# Function
This gene encodes a member of the bromodomain protein family. The bromodomain is a structural motif characteristic of proteins involved in chromatin-dependent regulation of transcription. This gene is deleted in Williams-Beuren syndrome, a developmental disorder caused by deletion of multiple genes at 7q11.23.[3]
# Animal models
Model organisms have been used in the study of BAZ1B function. A conditional knockout mouse line, called Baz1btm2a(KOMP)Wtsi,[4] 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.[5][6][7]
Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion.[7][8][9][10]
Six significant phenotypes were reported:[10]
- Fewer homozygous mutant mice survived to weaning than expected.
- Mutant mice had decreased body weights compared to wildtype control mice.
- Mutant mice showed increased activity, VO2 and energy expenditure, determined by indirect calorimetry.
- Radiography found teeth abnormalities.
- Dual-energy X-ray absorptiometry (DEXA) showed mutant female mice had a decrease in bone mineral density and content.
- Male heterozygous mice had higher bacterial counts after Salmonella infection.
# Interactions
BAZ1B has been shown to interact with:
- CHAF1A,[17]
- SMARCB1,[17]
- SMARCC1,[17]
- SMARCC2,[17]
- SUPT16H[17]
- TOP2B,[17] and
- VDR.[17] | https://www.wikidoc.org/index.php/BAZ1B | |
970c2a333c23a51cc202ed1558d0777689cc90d0 | wikidoc | BCAR1 | BCAR1
Breast cancer anti-estrogen resistance protein 1 is a protein that in humans is encoded by the BCAR1 gene.
# Gene
BCAR1 is localized on chromosome 16 on region q, on the negative strand and it consists of seven exons. Eight different gene isoforms have been identified that share the same sequence starting from the second exon onwards but are characterized by different starting sites. The longest isoform is called BCAR1-iso1 (RefSeq NM_001170714.1) and is 916 amino acids long, the other shorter isoforms start with an alternative first exon.
# Function
BCAR1 is a ubiquitously expressed adaptor molecule originally identified as the major substrate of v-Src and v-Crk . p130Cas/BCAR1 belongs to the Cas family of adaptor proteins and can act as a docking protein for several signalling partners. Due to its ability to associate with multiple signaling partners, p130Cas/BCAR1 contributes to the regulation to a variety of signaling pathways leading to cell adhesion, migration, invasion, apoptosis, hypoxia and mechanical forces. p130Cas/BCAR1 plays a role in cell transformation and cancer progression and alterations of p130Cas/BCAR1 expression and the resulting activation of selective signalling are determinants for the occurrence of different types of human tumors.
Due to the capacity of p130Cas/BCAR1, as an adaptor protein, to interact with multiple partners and to be regulated by phosphorylation and dephosphorylation, its expression and phosphorylation can lead to a wide range of functional consequences. Among the regulators of p130Cas/BCAR1 tyrosine phosphorylation, receptor tyrosine kinases (RTKs) and integrins play a prominent role. RTK-dependent p130Cas/BCAR1 tyrosine phosphorylation and the subsequent binding with specific downstream signaling molecule modulate cell processes such as actin cytoskeleton remodeling, cell adhesion, proliferation, migration, invasion and survival. Integrin-mediated p130Cas/BCAR1 phosphorylation upon adhesion to extracellular matrix (ECM) induces downstream signaling that is required for allowing cells to spread and migrate on the ECM.
Both RTKs and integrin activation affect p130Cas/BCAR1 tyrosine phosphorylation and represent an efficient means by which cells utilize signals coming from growth factors and integrin activation to coordinate cell responses. Additionally, p130Cas/BCAR1 tyrosine phosphorylation on its substrate domain can be induced by cell stretching subsequent to changes in the rigidity of the extracellular matrix, allowing cells to respond to mechanical force changes in the cell environment.
# Cas-Family
p130Cas/BCAR1 is a member of the Cas family (Crk-associated substrate) of adaptor proteins which is characterized by the presence of multiple conserved motifs for protein–protein interactions, and by extensive tyrosine and serine phosphorylations. The Cas family comprises other three members: NEDD9 (Neural precursor cell expressed, developmentally down-regulated 9, also called Human enhancer of filamentation 1, HEF-1 or Cas-L), EFS (Embryonal Fyn-associated substrate), and CASS4 (Cas scaffolding protein family member 4). These Cas proteins have a high structural homology, characterized by the presence of multiple protein interaction domains and phosphorylation motifs through which Cas family members can recruit effector proteins. However, despite the high degree of similarity, their temporal expression, tissue distribution and functional roles are distinct and not overlapping. Notably, the knock-out of p130Cas/BCAR1 in mice is embryonic lethal, suggesting that other family members do not show an overlapping role in development.
# Structure
p130Cas/BCAR1 is a scaffold protein characterized by several structural domains. It possesses an amino N-terminal Src-homology 3 domain (SH3) domain, followed by a proline-rich domain (PRR) and a substrate domain (SD). The substrate domain consists of 15 repeats of the YxxP consensus phosphorylation motif for Src family kinases (SFKs). Following the substrate domain is the serine-rich domain, which forms a four-helix bundle. This acts as a protein-interaction motif, similar to those found in other adhesion-related proteins such as focal adhesion kinase (FAK) and vinculin. The remaining carboxy-terminal sequence contains a bipartite Src-binding domain (residues 681–713) able to bind both the SH2 and SH3 domains of Src.
p130Cas/BCAR1 can undergo extensive changes in tyrosine phosphorylation that occur predominantly in the 15 YxxP repeats within the substrate domain and represent the major post-translational modification of p130Cas/BCAR1. p130Cas/BCAR1 tyrosine phosphorylation can result from a diverse range of extracellular stimuli, including growth factors, integrin activation, vasoactive hormones and peptides ligands for G-protein coupled receptors. These stimuli triggers p130Cas/BCAR1 tyrosine phosphorylation and its translocation from cytosol to the cell membrane.
# Clinical significance
Given the ability of p130Cas/BCAR1 scaffold protein to convey and integrate different type of signals and subsequently to regulate key cellular functions such as adhesion, migration, invasion, proliferation and survival, the existence of a strong correlation between deregulated p130Cas/BCAR1 expression and cancer was inferred. Deregulated expression of p130Cas/BCAR1 has been identified in several cancer types. Altered levels of p130Cas/BCAR1 expression in cancers can result from gene amplification, transcription upregulation or changes in protein stability. Overexpression of p130Cas/BCAR1 has been detected in human breast cancer, prostate cancer, ovarian cancer, lung cancer, colorectal cancer, hepatocellular carcinoma, glioma, melanoma, anaplastic large cell lymphoma and chronic myelogenous leukaemia. The presence of aberrant levels of hyperphosphorylated p130Cas/BCAR1 strongly promotes cell proliferation, migration, invasion, survival, angiogenesis and drug resistance. It has been demonstrated that high levels of p130Cas/BCAR1 expression in breast cancer correlate with worse prognosis, increased probability to develop metastasis and resistance to therapy. Conversely, lowering the amount of p130Cas/BCAR1 expression in ovarian, breast and prostate cancer is sufficient to block tumor growth and progression of cancer cells.
p130Cas/BCAR1 has potential uses as a diagnostic and prognostic marker for some human cancers. Since lowering p130Cas/BCAR1 in tumor cells is sufficient to halt their transformation and progression, it is conceivable to propose p130Cas/BCAR1 may represent a therapeutic target. However, the non-catalytic nature of p130Cas/BCAR1 makes difficult to develop specific inhibitors. | BCAR1
Breast cancer anti-estrogen resistance protein 1 is a protein that in humans is encoded by the BCAR1 gene.[1][2]
# Gene
BCAR1 is localized on chromosome 16 on region q, on the negative strand and it consists of seven exons. Eight different gene isoforms have been identified that share the same sequence starting from the second exon onwards but are characterized by different starting sites. The longest isoform is called BCAR1-iso1 (RefSeq NM_001170714.1) and is 916 amino acids long, the other shorter isoforms start with an alternative first exon.
# Function
BCAR1 is a ubiquitously expressed adaptor molecule originally identified as the major substrate of v-Src and v-Crk . p130Cas/BCAR1 belongs to the Cas family of adaptor proteins and can act as a docking protein for several signalling partners.[3] Due to its ability to associate with multiple signaling partners, p130Cas/BCAR1 contributes to the regulation to a variety of signaling pathways leading to cell adhesion, migration, invasion, apoptosis, hypoxia and mechanical forces. p130Cas/BCAR1 plays a role in cell transformation and cancer progression and alterations of p130Cas/BCAR1 expression and the resulting activation of selective signalling are determinants for the occurrence of different types of human tumors.[3]
Due to the capacity of p130Cas/BCAR1, as an adaptor protein, to interact with multiple partners and to be regulated by phosphorylation and dephosphorylation, its expression and phosphorylation can lead to a wide range of functional consequences. Among the regulators of p130Cas/BCAR1 tyrosine phosphorylation, receptor tyrosine kinases (RTKs) and integrins play a prominent role. RTK-dependent p130Cas/BCAR1 tyrosine phosphorylation and the subsequent binding with specific downstream signaling molecule modulate cell processes such as actin cytoskeleton remodeling, cell adhesion, proliferation, migration, invasion and survival.[4] Integrin-mediated p130Cas/BCAR1 phosphorylation upon adhesion to extracellular matrix (ECM) induces downstream signaling that is required for allowing cells to spread and migrate on the ECM.[5]
Both RTKs and integrin activation affect p130Cas/BCAR1 tyrosine phosphorylation[6] and represent an efficient means by which cells utilize signals coming from growth factors and integrin activation to coordinate cell responses. Additionally, p130Cas/BCAR1 tyrosine phosphorylation on its substrate domain can be induced by cell stretching subsequent to changes in the rigidity of the extracellular matrix, allowing cells to respond to mechanical force changes in the cell environment.[7]
# Cas-Family
p130Cas/BCAR1 is a member of the Cas family (Crk-associated substrate) of adaptor proteins which is characterized by the presence of multiple conserved motifs for protein–protein interactions, and by extensive tyrosine and serine phosphorylations. The Cas family comprises other three members: NEDD9 (Neural precursor cell expressed, developmentally down-regulated 9, also called Human enhancer of filamentation 1, HEF-1 or Cas-L), EFS (Embryonal Fyn-associated substrate), and CASS4 (Cas scaffolding protein family member 4).[8] These Cas proteins have a high structural homology, characterized by the presence of multiple protein interaction domains and phosphorylation motifs through which Cas family members can recruit effector proteins. However, despite the high degree of similarity, their temporal expression, tissue distribution and functional roles are distinct and not overlapping. Notably, the knock-out of p130Cas/BCAR1 in mice is embryonic lethal, suggesting that other family members do not show an overlapping role in development.[8][9]
# Structure
p130Cas/BCAR1 is a scaffold protein characterized by several structural domains. It possesses an amino N-terminal Src-homology 3 domain (SH3) domain, followed by a proline-rich domain (PRR) and a substrate domain (SD). The substrate domain consists of 15 repeats of the YxxP consensus phosphorylation motif for Src family kinases (SFKs). Following the substrate domain is the serine-rich domain, which forms a four-helix bundle. This acts as a protein-interaction motif, similar to those found in other adhesion-related proteins such as focal adhesion kinase (FAK) and vinculin. The remaining carboxy-terminal sequence contains a bipartite Src-binding domain (residues 681–713) able to bind both the SH2 and SH3 domains of Src.[10][11]
p130Cas/BCAR1 can undergo extensive changes in tyrosine phosphorylation that occur predominantly in the 15 YxxP repeats within the substrate domain and represent the major post-translational modification of p130Cas/BCAR1. p130Cas/BCAR1 tyrosine phosphorylation can result from a diverse range of extracellular stimuli, including growth factors, integrin activation, vasoactive hormones and peptides ligands for G-protein coupled receptors. These stimuli triggers p130Cas/BCAR1 tyrosine phosphorylation and its translocation from cytosol to the cell membrane.[11]
# Clinical significance
Given the ability of p130Cas/BCAR1 scaffold protein to convey and integrate different type of signals and subsequently to regulate key cellular functions such as adhesion, migration, invasion, proliferation and survival, the existence of a strong correlation between deregulated p130Cas/BCAR1 expression and cancer was inferred. Deregulated expression of p130Cas/BCAR1 has been identified in several cancer types. Altered levels of p130Cas/BCAR1 expression in cancers can result from gene amplification, transcription upregulation or changes in protein stability. Overexpression of p130Cas/BCAR1 has been detected in human breast cancer, prostate cancer, ovarian cancer, lung cancer, colorectal cancer, hepatocellular carcinoma, glioma, melanoma, anaplastic large cell lymphoma and chronic myelogenous leukaemia.[12] The presence of aberrant levels of hyperphosphorylated p130Cas/BCAR1 strongly promotes cell proliferation, migration, invasion, survival, angiogenesis and drug resistance.[9] It has been demonstrated that high levels of p130Cas/BCAR1 expression in breast cancer correlate with worse prognosis, increased probability to develop metastasis and resistance to therapy.[13][14][15][16][17] Conversely, lowering the amount of p130Cas/BCAR1 expression in ovarian, breast and prostate cancer is sufficient to block tumor growth and progression of cancer cells.[3][17][18]
p130Cas/BCAR1 has potential uses as a diagnostic and prognostic marker for some human cancers. Since lowering p130Cas/BCAR1 in tumor cells is sufficient to halt their transformation and progression, it is conceivable to propose p130Cas/BCAR1 may represent a therapeutic target. However, the non-catalytic nature of p130Cas/BCAR1 makes difficult to develop specific inhibitors.[19] | https://www.wikidoc.org/index.php/BCAR1 | |
b044d43ba66fc0486dea802c81047c45fa2a62d0 | wikidoc | BCCIP | BCCIP
BRCA2 and CDKN1A-interacting protein is a protein that in humans is encoded by the BCCIP gene.
This gene product was isolated on the basis of its interaction with BRCA2 and p21 proteins. It is an evolutionarily conserved nuclear protein with multiple interacting domains. The N-terminal half shares moderate homology with regions of calmodulin and M-calpain, suggesting that it may also bind calcium. Functional studies indicate that this protein may be an important cofactor for BRCA2 in tumor suppression, and a modulator of CDK2 kinase activity via p21. Several transcript variants encoding different isoforms have been described for this gene.
# Interactions
BCCIP has been shown to interact with BRCA2, P21, and PTPmu (PTPRM) | BCCIP
BRCA2 and CDKN1A-interacting protein is a protein that in humans is encoded by the BCCIP gene.[1][2][3]
This gene product was isolated on the basis of its interaction with BRCA2 and p21 proteins. It is an evolutionarily conserved nuclear protein with multiple interacting domains. The N-terminal half shares moderate homology with regions of calmodulin and M-calpain, suggesting that it may also bind calcium. Functional studies indicate that this protein may be an important cofactor for BRCA2 in tumor suppression, and a modulator of CDK2 kinase activity via p21. Several transcript variants encoding different isoforms have been described for this gene.[3]
# Interactions
BCCIP has been shown to interact with BRCA2,[1] P21,[2] and PTPmu (PTPRM)[4] | https://www.wikidoc.org/index.php/BCCIP | |
cab0391b6420b054076742a7c8804a8ab74de05f | wikidoc | BCKDK | BCKDK
Branched chain ketoacid dehydrogenase kinase (BCKDK) is an enzyme encoded by the BCKDK gene on chromosome 16. This enzyme is part of the mitochondrial protein kinases family and it is a regulator of the valine, leucine, and isoleucine catabolic pathways. BCKDK is found in the mitochondrial matrix and the prevalence of it depends on the type of cell. Liver cells tend to have the lowest concentration of BCKDK, whereas skeletal muscle cells have the highest amount. Abnormal activity of this enzyme often leads to diseases such as maple syrup urine disease and cachexia.
# Structure
BCKDK’s structure consists of a characteristic nucleotide-binding domain along with a four-helix bundle domain similar to certain aspects of protein histidine kinases, which are involved in two-component signal transduction systems. BCKDK is also a dimer with a Leu389 residue located between the dimers and this dimerization is seen to be essential for its kinase activity and protein stability. Moreover, it is made up of 382 amino acids and has a molecular weight of 43 kDa. The gene BCKDK is located at 16p11.2, has an exon count of 11, and it lacks a TATA-box and an initiator element.
# Function
BCKDK regulates the activity of branched-chain α-ketoacid dehydrogenase complex (BCKD) through phosphorylation and inactivation. This inactivation results in increased branched-chain amino acids (BCAA), which is seen to reduce oxidative stress; however, having too much BCAA has been proven to be toxic to humans. Therefore, BCKDK is a vital tool to assist with BCAA homeostasis. As stated earlier, BCKDK concentrations vary depending on the type of tissue that is observed, whereas BCKD’s concentration is the same in any tissue. Although BCKD concentration is constant, the amount of BCKDK determines the activity of the dehydrogenase complex. Since liver tissue is seen to have the lowest concentration of BCKDK, the activity of BCKD is seen to be the highest, delineating the fact that the BCKD kinase inversely affects the BCKD activity.
# Clinical significance
Abnormalities in BCKD activity often leads to pathological conditions which is why BCKDK is needed to regulate it. Often, mutations in the BCKDK gene occur creating the deviation in BCKD behavior. Exceedingly high BCKD complex activity increases branched-chain amino acid catabolism and protein degradation in skeletal muscle, which is a distinctive feature for cachexia. Deficiencies in BCKD activity have been the main cause in the rare metabolism maple syrup urine disease that can lead to mental retardation, brain edema, seizures, coma, and death if not treated correctly by lifelong limitation of branched-chain amino acid intake. Because BCKDK regulates BCKD which in turn catalyzes BCAA, BCKDK is one of the factors that determines the concentration of BCAA levels. High BCAA levels can lead to insulin resistance and can be a potential marker for type 2 diabetes. The amalgamation of BCAA can also lead to congenital heart diseases and heart failure. Furthermore, low levels of BCAA have been described as a cause of comorbid intellectual disability, autism, and epilepsy.
# Interactions
BCKDK has been seen to interact with:
- BCKD | BCKDK
Branched chain ketoacid dehydrogenase kinase (BCKDK) is an enzyme encoded by the BCKDK gene on chromosome 16. This enzyme is part of the mitochondrial protein kinases family and it is a regulator of the valine, leucine, and isoleucine catabolic pathways.[1] BCKDK is found in the mitochondrial matrix and the prevalence of it depends on the type of cell. Liver cells tend to have the lowest concentration of BCKDK, whereas skeletal muscle cells have the highest amount.[2][3] Abnormal activity of this enzyme often leads to diseases such as maple syrup urine disease and cachexia.
# Structure
BCKDK’s structure consists of a characteristic nucleotide-binding domain along with a four-helix bundle domain similar to certain aspects of protein histidine kinases, which are involved in two-component signal transduction systems. BCKDK is also a dimer with a Leu389 residue located between the dimers and this dimerization is seen to be essential for its kinase activity and protein stability.[4] Moreover, it is made up of 382 amino acids and has a molecular weight of 43 kDa.[2] The gene BCKDK is located at 16p11.2, has an exon count of 11, and it lacks a TATA-box and an initiator element.[1][3]
# Function
BCKDK regulates the activity of branched-chain α-ketoacid dehydrogenase complex (BCKD) through phosphorylation and inactivation. This inactivation results in increased branched-chain amino acids (BCAA), which is seen to reduce oxidative stress; however, having too much BCAA has been proven to be toxic to humans. Therefore, BCKDK is a vital tool to assist with BCAA homeostasis.[5][6] As stated earlier, BCKDK concentrations vary depending on the type of tissue that is observed, whereas BCKD’s concentration is the same in any tissue. Although BCKD concentration is constant, the amount of BCKDK determines the activity of the dehydrogenase complex. Since liver tissue is seen to have the lowest concentration of BCKDK, the activity of BCKD is seen to be the highest, delineating the fact that the BCKD kinase inversely affects the BCKD activity.[3]
# Clinical significance
Abnormalities in BCKD activity often leads to pathological conditions which is why BCKDK is needed to regulate it. Often, mutations in the BCKDK gene occur creating the deviation in BCKD behavior. Exceedingly high BCKD complex activity increases branched-chain amino acid catabolism and protein degradation in skeletal muscle, which is a distinctive feature for cachexia. Deficiencies in BCKD activity have been the main cause in the rare metabolism maple syrup urine disease that can lead to mental retardation, brain edema, seizures, coma, and death if not treated correctly by lifelong limitation of branched-chain amino acid intake.[3] Because BCKDK regulates BCKD which in turn catalyzes BCAA, BCKDK is one of the factors that determines the concentration of BCAA levels. High BCAA levels can lead to insulin resistance and can be a potential marker for type 2 diabetes.[6] The amalgamation of BCAA can also lead to congenital heart diseases and heart failure. Furthermore, low levels of BCAA have been described as a cause of comorbid intellectual disability, autism, and epilepsy.[4]
# Interactions
BCKDK has been seen to interact with:
- BCKD [2] | https://www.wikidoc.org/index.php/BCKDK | |
119d8ff8a9726387b9a7e0ff6375d1f32947a317 | wikidoc | Bcl-2 | Bcl-2
Bcl-2 (B-cell lymphoma 2), encoded in humans by the BCL2 gene, is the founding member of the Bcl-2 family of regulator proteins that regulate cell death (apoptosis), by either inducing (pro-apoptotic) or inhibiting (anti-apoptotic) apoptosis.
Bcl-2 derives its name from B-cell lymphoma 2, as it is the second member of a range of proteins initially described in chromosomal translocations involving chromosomes 14 and 18 in follicular lymphomas. Orthologs (such as Bcl2 in mice) have been identified in numerous mammals for which complete genome data are available.
Like BCL3, BCL5, BCL6, BCL7A, BCL9, and BCL10, it has clinical significance in lymphoma.
# Isoforms
The two isoforms of Bcl-2, Isoform 1, also known as 1G5M, and Isoform 2, also known as 1G5O/1GJH, exhibit a similar fold. However, results in the ability of these isoforms to bind to the BAD and BAK proteins, as well as in the structural topology and electrostatic potential of the binding groove, suggest differences in antiapoptotic activity for the two isoforms.
# Normal physiological function
BCL-2 is localized to the outer membrane of mitochondria, where it plays an important role in promoting cellular survival and inhibiting the actions of pro-apoptotic proteins. The pro-apoptotic proteins in the BCL-2 family, including Bax and Bak, normally act on the mitochondrial membrane to promote permeabilization and release of cytochrome C and ROS, that are important signals in the apoptosis cascade. These pro-apoptotic proteins are in turn activated by BH3-only proteins, and are inhibited by the function of BCL-2 and its relative BCL-Xl.
There are additional non-canonical roles of BCL-2 that are being explored. BCL-2 is known to regulate mitochondrial dynamics, and is involved in the regulation of mitochondrial fusion and fission. Additionally, in pancreatic beta-cells, BCL-2 and BCL-Xl are known to be involved in controlling metabolic activity and insulin secretion, with inhibition of BCL-2/Xl showing increasing metabolic activity, but also additional ROS production; this suggests it has a protective metabolic effect in conditions of high demand.
# Role in disease
Damage to the Bcl-2 gene has been identified as a cause of a number of cancers, including melanoma, breast, prostate, chronic lymphocytic leukemia, and lung cancer, and a possible cause of schizophrenia and autoimmunity. It is also a cause of resistance to cancer treatments.
## Cancer
Cancer can be seen as a disturbance in the homeostatic balance between cell growth and cell death. Over-expression of anti-apoptotic genes, and under-expression of pro-apoptotic genes, can result in the lack of cell death that is characteristic of cancer. An example can be seen in lymphomas. The over-expression of the anti-apoptotic Bcl-2 protein in lymphocytes alone does not cause cancer. But simultaneous over-expression of Bcl-2 and the proto-oncogene myc may produce aggressive B-cell malignancies including lymphoma. In follicular lymphoma, a chromosomal translocation commonly occurs between the fourteenth and the eighteenth chromosomes — t(14;18) — which places the Bcl-2 gene from chromosome 18 next to the immunoglobulin heavy chain locus on chromosome 14. This fusion gene is deregulated, leading to the transcription of excessively high levels of Bcl-2. This decreases the propensity of these cells for apoptosis.
## Auto-immune diseases
Apoptosis plays an active role in regulating the immune system. When it is functional, it can cause immune unresponsiveness to self-antigens via both central and peripheral tolerance. In the case of defective apoptosis, it may contribute to etiological aspects of autoimmune diseases. The autoimmune disease type 1 diabetes can be caused by defective apoptosis, which leads to aberrant T cell AICD and defective peripheral tolerance. Due to the fact that dendritic cells are the immune system's most important antigen-presenting cells, their activity must be tightly regulated by mechanisms such as apoptosis. Researchers have found that mice containing dendritic cells that are Bim -/-, thus unable to induce effective apoptosis, suffer autoimmune diseases more so than those that have normal dendritic cells. Other studies have shown that dendritic cell lifespan may be partly controlled by a timer dependent on anti-apoptotic Bcl-2.
## Other
Apoptosis plays an important role in regulating a variety of diseases. For example, schizophrenia is a psychiatric disorder in which an abnormal ratio of pro- and anti-apoptotic factors may contribute towards pathogenesis. Some evidence suggests that this may result from abnormal expression of Bcl-2 and increased expression of caspase-3.
# Diagnostic use
Antibodies to Bcl-2 can be used with immunohistochemistry to identify cells containing the antigen. In healthy tissue, these antibodies react with B-cells in the mantle zone, as well as some T-cells. However, positive cells increase considerably in follicular lymphoma, as well as many other forms of cancer. In some cases, the presence or absence of Bcl-2 staining in biopsies may be significant for the patient's prognosis or likelihood of relapse.
# Targeted therapies
Targeted and selective Bcl-2 inhibitors that have been in development or are currently in the clinic include:
## Oblimersen
An antisense oligonucleotide drug, oblimersen (G3139), was developed by Genta Incorporated to target Bcl-2. An antisense DNA or RNA strand is non-coding and complementary to the coding strand (which is the template for producing respectively RNA or protein). An antisense drug is a short sequence of RNA that hybridises with and inactivates mRNA, preventing the protein from being formed.
Human lymphoma cell proliferation (with t(14;18) translocation) could be inhibited by antisense RNA targeted at the start codon region of Bcl-2 mRNA. In vitro studies led to the identification of Genasense, which is complementary to the first 6 codons of Bcl-2 mRNA.
These showed successful results in Phase I/II trials for lymphoma. A large Phase III trial was launched in 2004. As of 2016, the drug had not been approved and its developer was out of business.
## ABT-737 and navitoclax (ABT-263)
In the mid-2000s, Abbott Laboratories developed a novel inhibitor of Bcl-2, Bcl-xL and Bcl-w, known as ABT-737. This compound is part of a group of BH3 mimetic small molecule inhibitors (SMI) that target these Bcl-2 family proteins, but not A1 or Mcl-1. ABT-737 is superior to previous BCL-2 inhibitors given its higher affinity for Bcl-2, Bcl-xL and Bcl-w. In vitro studies showed that primary cells from patients with B-cell malignancies are sensitive to ABT-737. ABT-737 does not directly induce apoptosis; it enhances the effects of apoptotic signals and causes single-agent-mechanism-based killing of cells in small-cell lung carcinoma and lymphoma lines.
In animal models, it improves survival, causes tumor regression and cures a high percentage of mice. In preclinical studies utilizing patient xenografts, ABT-737 showed efficacy for treating lymphoma and other blood cancers. Because of its unfavorable pharmacologic properties ABT-737 is not appropriate for clinical trials, while its orally bioavailable derivative navitoclax (ABT-263) has similar activity on small cell lung cancer (SCLC) cell lines and has entered clinical trials. While clinical responses with navitoclax were promising, mechanistic dose-limiting thrombocytopoenia was observed in patients under treatment due to Bcl-xL inhibition in platelets.
## Venetoclax (ABT-199)
Due to dose-limiting thrombocytopoenia of navitoclax as a result of Bcl-xL inhibition, Abbvie successfully developed the highly selective inhibitor venetoclax (ABT-199), which inhibits Bcl-2, but not Bcl-xL or Bcl-w. Clinical trials studied the effects of venetoclax, a BH3-mimetic drug designed to block the function of the Bcl-2 protein, on patients with chronic lymphocytic leukemia (CLL). Good responses have been reported and thrombocytopoenia was no longer observed. A phase 3 trial started in Dec 2015.
It was approved by the US FDA in April 2016 as a second-line treatment for CLL associated with 17-p deletion. This was the first FDA approval of a BCL-2 inhibitor. In June 2018, the FDA broadened the approval for anyone with CLL or small lymphocytic lymphoma, with or without 17p deletion, still as a second-line treatment.
# Interactions
Bcl-2 has been shown to interact with:
- BAK1,
- BCAP31,
- BCL2-like 1,
- BCL2L11,
- BECN1,
- BID,
- BMF,
- BNIP2,
- BNIP3,
- BNIPL,
- BAD
- BAX,
- BIK,
- C-Raf,
- CAPN2,
- CASP8,
- Cdk1,
- HRK,
- IRS1,
- Myc,
- NR4A1,
- Noxa,
- PPP2CA,
- PSEN1,
- RAD9A,
- RRAS,
- RTN4,
- SMN1,
- SOD1, and
- TP53BP2. | Bcl-2
Bcl-2 (B-cell lymphoma 2), encoded in humans by the BCL2 gene, is the founding member of the Bcl-2 family of regulator proteins that regulate cell death (apoptosis), by either inducing (pro-apoptotic) or inhibiting (anti-apoptotic) apoptosis.[1][2]
Bcl-2 derives its name from B-cell lymphoma 2, as it is the second member of a range of proteins initially described in chromosomal translocations involving chromosomes 14 and 18 in follicular lymphomas. Orthologs[3] (such as Bcl2 in mice) have been identified in numerous mammals for which complete genome data are available.
Like BCL3, BCL5, BCL6, BCL7A, BCL9, and BCL10, it has clinical significance in lymphoma.
# Isoforms
The two isoforms of Bcl-2, Isoform 1, also known as 1G5M, and Isoform 2, also known as 1G5O/1GJH, exhibit a similar fold. However, results in the ability of these isoforms to bind to the BAD and BAK proteins, as well as in the structural topology and electrostatic potential of the binding groove, suggest differences in antiapoptotic activity for the two isoforms.[4]
# Normal physiological function
BCL-2 is localized to the outer membrane of mitochondria, where it plays an important role in promoting cellular survival and inhibiting the actions of pro-apoptotic proteins. The pro-apoptotic proteins in the BCL-2 family, including Bax and Bak, normally act on the mitochondrial membrane to promote permeabilization and release of cytochrome C and ROS, that are important signals in the apoptosis cascade. These pro-apoptotic proteins are in turn activated by BH3-only proteins, and are inhibited by the function of BCL-2 and its relative BCL-Xl.[5]
There are additional non-canonical roles of BCL-2 that are being explored. BCL-2 is known to regulate mitochondrial dynamics, and is involved in the regulation of mitochondrial fusion and fission. Additionally, in pancreatic beta-cells, BCL-2 and BCL-Xl are known to be involved in controlling metabolic activity and insulin secretion, with inhibition of BCL-2/Xl showing increasing metabolic activity,[6] but also additional ROS production; this suggests it has a protective metabolic effect in conditions of high demand.[7]
# Role in disease
Damage to the Bcl-2 gene has been identified as a cause of a number of cancers, including melanoma, breast, prostate, chronic lymphocytic leukemia, and lung cancer, and a possible cause of schizophrenia and autoimmunity. It is also a cause of resistance to cancer treatments.[citation needed]
## Cancer
Cancer can be seen as a disturbance in the homeostatic balance between cell growth and cell death. Over-expression of anti-apoptotic genes, and under-expression of pro-apoptotic genes, can result in the lack of cell death that is characteristic of cancer. An example can be seen in lymphomas. The over-expression of the anti-apoptotic Bcl-2 protein in lymphocytes alone does not cause cancer. But simultaneous over-expression of Bcl-2 and the proto-oncogene myc may produce aggressive B-cell malignancies including lymphoma.[8] In follicular lymphoma, a chromosomal translocation commonly occurs between the fourteenth and the eighteenth chromosomes — t(14;18) — which places the Bcl-2 gene from chromosome 18 next to the immunoglobulin heavy chain locus on chromosome 14. This fusion gene is deregulated, leading to the transcription of excessively high levels of Bcl-2.[9] This decreases the propensity of these cells for apoptosis.
## Auto-immune diseases
Apoptosis plays an active role in regulating the immune system. When it is functional, it can cause immune unresponsiveness to self-antigens via both central and peripheral tolerance. In the case of defective apoptosis, it may contribute to etiological aspects of autoimmune diseases.[10] The autoimmune disease type 1 diabetes can be caused by defective apoptosis, which leads to aberrant T cell AICD and defective peripheral tolerance. Due to the fact that dendritic cells are the immune system's most important antigen-presenting cells, their activity must be tightly regulated by mechanisms such as apoptosis. Researchers have found that mice containing dendritic cells that are Bim -/-, thus unable to induce effective apoptosis, suffer autoimmune diseases more so than those that have normal dendritic cells.[10] Other studies have shown that dendritic cell lifespan may be partly controlled by a timer dependent on anti-apoptotic Bcl-2.[10]
## Other
Apoptosis plays an important role in regulating a variety of diseases. For example, schizophrenia is a psychiatric disorder in which an abnormal ratio of pro- and anti-apoptotic factors may contribute towards pathogenesis.[11] Some evidence suggests that this may result from abnormal expression of Bcl-2 and increased expression of caspase-3.[11]
# Diagnostic use
Antibodies to Bcl-2 can be used with immunohistochemistry to identify cells containing the antigen. In healthy tissue, these antibodies react with B-cells in the mantle zone, as well as some T-cells. However, positive cells increase considerably in follicular lymphoma, as well as many other forms of cancer. In some cases, the presence or absence of Bcl-2 staining in biopsies may be significant for the patient's prognosis or likelihood of relapse.[12]
# Targeted therapies
Targeted and selective Bcl-2 inhibitors that have been in development or are currently in the clinic include:
## Oblimersen
An antisense oligonucleotide drug, oblimersen (G3139), was developed by Genta Incorporated to target Bcl-2. An antisense DNA or RNA strand is non-coding and complementary to the coding strand (which is the template for producing respectively RNA or protein). An antisense drug is a short sequence of RNA that hybridises with and inactivates mRNA, preventing the protein from being formed.
Human lymphoma cell proliferation (with t(14;18) translocation) could be inhibited by antisense RNA targeted at the start codon region of Bcl-2 mRNA. In vitro studies led to the identification of Genasense, which is complementary to the first 6 codons of Bcl-2 mRNA.[13]
These showed successful results in Phase I/II trials for lymphoma. A large Phase III trial was launched in 2004.[14] As of 2016, the drug had not been approved and its developer was out of business.[15]
## ABT-737 and navitoclax (ABT-263)
In the mid-2000s, Abbott Laboratories developed a novel inhibitor of Bcl-2, Bcl-xL and Bcl-w, known as ABT-737. This compound is part of a group of BH3 mimetic small molecule inhibitors (SMI) that target these Bcl-2 family proteins, but not A1 or Mcl-1. ABT-737 is superior to previous BCL-2 inhibitors given its higher affinity for Bcl-2, Bcl-xL and Bcl-w. In vitro studies showed that primary cells from patients with B-cell malignancies are sensitive to ABT-737.[16] ABT-737 does not directly induce apoptosis; it enhances the effects of apoptotic signals and causes single-agent-mechanism-based killing of cells in small-cell lung carcinoma and lymphoma lines.[citation needed]
In animal models, it improves survival, causes tumor regression and cures a high percentage of mice.[17] In preclinical studies utilizing patient xenografts, ABT-737 showed efficacy for treating lymphoma and other blood cancers.[18] Because of its unfavorable pharmacologic properties ABT-737 is not appropriate for clinical trials, while its orally bioavailable derivative navitoclax (ABT-263) has similar activity on small cell lung cancer (SCLC) cell lines and has entered clinical trials.[19] While clinical responses with navitoclax were promising, mechanistic dose-limiting thrombocytopoenia was observed in patients under treatment due to Bcl-xL inhibition in platelets.[20][21][22]
## Venetoclax (ABT-199)
Due to dose-limiting thrombocytopoenia of navitoclax as a result of Bcl-xL inhibition, Abbvie successfully developed the highly selective inhibitor venetoclax (ABT-199), which inhibits Bcl-2, but not Bcl-xL or Bcl-w.[23] Clinical trials studied the effects of venetoclax, a BH3-mimetic drug designed to block the function of the Bcl-2 protein, on patients with chronic lymphocytic leukemia (CLL).[24][25] Good responses have been reported and thrombocytopoenia was no longer observed.[25][26] A phase 3 trial started in Dec 2015.[27]
It was approved by the US FDA in April 2016 as a second-line treatment for CLL associated with 17-p deletion.[28] This was the first FDA approval of a BCL-2 inhibitor.[28] In June 2018, the FDA broadened the approval for anyone with CLL or small lymphocytic lymphoma, with or without 17p deletion, still as a second-line treatment.[29]
# Interactions
Bcl-2 has been shown to interact with:
- BAK1,[30][31]
- BCAP31,[32]
- BCL2-like 1,[30][33]
- BCL2L11,[34][35][36]
- BECN1,[37]
- BID,[34][38]
- BMF,[39]
- BNIP2,[40][41]
- BNIP3,[41][42]
- BNIPL,[40][43]
- BAD[34][44]
- BAX,[30][45][46][47]
- BIK,[34][48]
- C-Raf,[49]
- CAPN2,[50]
- CASP8,[51][52]
- Cdk1,[53][54]
- HRK,[34][55]
- IRS1,[56]
- Myc,[57]
- NR4A1,[30]
- Noxa,[34][58]
- PPP2CA,[59]
- PSEN1,[60]
- RAD9A,[45]
- RRAS,[61]
- RTN4,[62]
- SMN1,[63]
- SOD1,[64] and
- TP53BP2.[65] | https://www.wikidoc.org/index.php/BCL-2 | |
0a80dafb15ef3fc51689ed94dc5cd4e72d3fdfe4 | wikidoc | BCS1L | BCS1L
Mitochondrial chaperone BCS1 (BCS1L), also known as BCS1 homolog, ubiquinol-cytochrome c reductase complex chaperone (h-BCS1), is a protein that in humans is encoded by the BCS1L gene. BCS1L is a chaperone protein involved in the assembly of Ubiquinol Cytochrome c Reductase (complex III), which is located in the inner mitochondrial membrane and is part of the electron transport chain. Mutations in this gene are associated with mitochondrial complex III deficiency (nuclear, 1), GRACILE syndrome, and Bjoernstad syndrome.
# Structure
BCS1L is located on the q arm of chromosome 2 in position 35 and has 10 exons. The BCS1L gene produces a 47.5 kDa protein composed of 419 amino acids. The protein encoded by BCS1L belongs to the AAA ATPase family, BCS1 subfamily. BCS1L is a phosphoprotein and chaperone for Ubiquinol Cytochrome c Reductase assembly. It contains a nucleotide binding site for ATP-binding. BCS1L does not contain a mitochondrial targeting sequence but experimental studies confirm that it is imported into mitochondria. A conserved domain at the N-terminus of BCS1L is responsible for the import and intramitochondrial sorting. Associating to the inner mitochondrial membrane, BCS1L has a transmembrane domain in between two topological domains, passing through the inner mitochondrial membrane once. The majority of the protein is in the mitochondrial matrix. Several alternatively spliced transcripts encoding two different isoforms have been described.
# Function
BCS1L encodes a protein that is located in the inner mitochondrial membrane and involved in the assembly of Ubiquinol Cytochrome c Reductase (complex III). Complex III plays an important role in the mitochondrial respiratory chain by transferring electrons from the Rieske iron-sulfur protein to cytochrome c. BCS1L is essential for this process through its role in the maintenance of mitochondrial tubular networks, respiratory chain assembly, and formation of the LETM1 complex.
# Clinical Significance
Variants of BCS1L have been associated with mitochondrial complex III deficiency, nuclear 1, GRACILE syndrome, and Bjoernstad syndrome. Mitochondrial complex III deficiency, nuclear 1 is a disorder of the mitochondrial respiratory chain resulting in reduced complex III activity and highly variable clinical features usually resulting in multi-system organ failure. Clinical features may include mitochondrial encephalopathy, psychomotor retardation, ataxia, severe failure to thrive, liver dysfunction, renal tubulopathy, muscle weakness, exercise intolerance, lactic acidosis, hypotonia, seizures, and optic atrophy. Pathogenic mutations have included R45C, R56X, T50A, R73C, P99L, R155P, V353M, G129R, R183C, F368I, and S277N. These mutations tend to affect the ATP-binding residues of BCS1L.
Growth retardation, aminoaciduria, cholestasis, iron overload, lactic acidosis, and early death (GRACILE) is a recessively inherited lethal disease that results in mutli-system organ failure. GRACILE is characterized by fetal growth retardation, lactic acidosis, aminoaciduria, cholestasis, and abnormalities in iron metabolism. Pathogenic mutations have included S78G, R144Q, and V327A.
Bjoernstad syndrome ia an autosomal recessive disease primarily affecting hearing. This disease is characterized by congenital hearing loss and twisted hairs, a condition known as pili torti, in which hair shafts are flattened at irregular intervals and twisted 180 degrees from the normal axis, making the hair extremely brittle. Pathogenic mutations have included Y301N, R184C, G35R, R114W, R183H, Q302E, and R306H. These mutations tend to affect the protein-protein interactions of BCS1L.
# Interactions
BCS1L has 11 protein-protein interactions with 8 of them being co-complex interactions. BCS1L has been found to interact with LETM1, DNAJA1, and DDX24. | BCS1L
Mitochondrial chaperone BCS1 (BCS1L), also known as BCS1 homolog, ubiquinol-cytochrome c reductase complex chaperone (h-BCS1), is a protein that in humans is encoded by the BCS1L gene. BCS1L is a chaperone protein involved in the assembly of Ubiquinol Cytochrome c Reductase (complex III), which is located in the inner mitochondrial membrane and is part of the electron transport chain. Mutations in this gene are associated with mitochondrial complex III deficiency (nuclear, 1), GRACILE syndrome, and Bjoernstad syndrome.[1][2][3]
# Structure
BCS1L is located on the q arm of chromosome 2 in position 35 and has 10 exons.[1] The BCS1L gene produces a 47.5 kDa protein composed of 419 amino acids.[4][5] The protein encoded by BCS1L belongs to the AAA ATPase family, BCS1 subfamily. BCS1L is a phosphoprotein and chaperone for Ubiquinol Cytochrome c Reductase assembly. It contains a nucleotide binding site for ATP-binding.[2][3] BCS1L does not contain a mitochondrial targeting sequence but experimental studies confirm that it is imported into mitochondria. A conserved domain at the N-terminus of BCS1L is responsible for the import and intramitochondrial sorting.[6] Associating to the inner mitochondrial membrane, BCS1L has a transmembrane domain in between two topological domains, passing through the inner mitochondrial membrane once. The majority of the protein is in the mitochondrial matrix.[2][3] Several alternatively spliced transcripts encoding two different isoforms have been described.[7]
# Function
BCS1L encodes a protein that is located in the inner mitochondrial membrane and involved in the assembly of Ubiquinol Cytochrome c Reductase (complex III). Complex III plays an important role in the mitochondrial respiratory chain by transferring electrons from the Rieske iron-sulfur protein to cytochrome c. BCS1L is essential for this process through its role in the maintenance of mitochondrial tubular networks, respiratory chain assembly, and formation of the LETM1 complex.[8][2][3]
# Clinical Significance
Variants of BCS1L have been associated with mitochondrial complex III deficiency, nuclear 1, GRACILE syndrome, and Bjoernstad syndrome. Mitochondrial complex III deficiency, nuclear 1 is a disorder of the mitochondrial respiratory chain resulting in reduced complex III activity and highly variable clinical features usually resulting in multi-system organ failure. Clinical features may include mitochondrial encephalopathy, psychomotor retardation, ataxia, severe failure to thrive, liver dysfunction, renal tubulopathy, muscle weakness, exercise intolerance, lactic acidosis, hypotonia, seizures, and optic atrophy. Pathogenic mutations have included R45C, R56X,[9][10][11] T50A,[12] R73C,[13] P99L, R155P, V353M,[14] G129R,[15][16] R183C, F368I,[17] and S277N. These mutations tend to affect the ATP-binding residues of BCS1L.[18][3][2]
Growth retardation, aminoaciduria, cholestasis, iron overload, lactic acidosis, and early death (GRACILE) is a recessively inherited lethal disease that results in mutli-system organ failure. GRACILE is characterized by fetal growth retardation, lactic acidosis, aminoaciduria, cholestasis, and abnormalities in iron metabolism. Pathogenic mutations have included S78G, R144Q, and V327A.[19][3][2]
Bjoernstad syndrome ia an autosomal recessive disease primarily affecting hearing. This disease is characterized by congenital hearing loss and twisted hairs, a condition known as pili torti, in which hair shafts are flattened at irregular intervals and twisted 180 degrees from the normal axis, making the hair extremely brittle. Pathogenic mutations have included Y301N,[20] R184C,[17] G35R, R114W, R183H, Q302E, and R306H. These mutations tend to affect the protein-protein interactions of BCS1L.[18][3][2]
# Interactions
BCS1L has 11 protein-protein interactions with 8 of them being co-complex interactions. BCS1L has been found to interact with LETM1, DNAJA1, and DDX24.[21] | https://www.wikidoc.org/index.php/BCS1L | |
efd495b7dde771acf3578a9644c0a2eb717a1d2c | wikidoc | BECN1 | BECN1
Beclin-1 is a protein that in humans is encoded by the BECN1 gene. Beclin-1 is a mammalian ortholog of the yeast autophagy-related gene 6 (Atg6) and BEC-1 in the C. elegans nematode. This protein interacts with either BCL-2 or PI3k class III, playing a critical role in the regulation of both autophagy and cell death.
# Role in disease
Beclin-1 plays an important role in tumorigenesis, and neurodegeneration, being implicated in the autophagic programmed cell death. Ovarian cancer with upregulated autophagy has a less aggressive behavior and is more responsive to chemotherapy.
Schizophrenia is associated with low levels of Beclin-1 in the hippocampus of the affected which causes diminished autophagy which in turn results in increased neuronal cell death.
# Interactions
BECN1 has been shown to interact with:
- Bcl-2
- BCL2L2
- GOPC
- MAP1LC3A
# Modulators | BECN1
Beclin-1 is a protein that in humans is encoded by the BECN1 gene.[1][2] Beclin-1 is a mammalian ortholog of the yeast autophagy-related gene 6 (Atg6) and BEC-1 in the C. elegans nematode.[3] This protein interacts with either BCL-2 or PI3k class III, playing a critical role in the regulation of both autophagy and cell death.
# Role in disease
Beclin-1 plays an important role in tumorigenesis, and neurodegeneration, being implicated in the autophagic programmed cell death.[4] Ovarian cancer with upregulated autophagy has a less aggressive behavior and is more responsive to chemotherapy.[5]
Schizophrenia is associated with low levels of Beclin-1 in the hippocampus of the affected which causes diminished autophagy which in turn results in increased neuronal cell death.[6]
# Interactions
BECN1 has been shown to interact with:
- Bcl-2[1]
- BCL2L2[7]
- GOPC[8]
- MAP1LC3A[5]
# Modulators | https://www.wikidoc.org/index.php/BECN1 | |
1940e0452e3847babbab3ce246a4383ea4f4bb6e | wikidoc | BIMU8 | BIMU8
BIMU-8 is a novel compound which acts on an area of the brain stem known as the pre-Botzinger complex.
# Explanation
The pre-Botzinger complex has been found to drive respiration. BIMU-8 stimulates this area of the brain, causing an increase in the rate of respiration. BIMU-8 acts as a selective 5HT4 agonist and is one of the first compounds to be developed that was selective for this serotonin receptor subtype.
# Practical use of BIMU-8
The most obvious practical use of BIMU-8 is to combine it with opiates in order to counteract the dangerous respiratory depressing properties of the latter. BIMU-8 does not affect the painkilling properties of opiates, which means that if combined with BIMU-8, large therapeutic doses of opiates could theoretically be given to humans without risking a decrease in breathing rate. Studies have shown BIMU-8 to be effective in rats at counteracting the respiratory depression caused by the potent opioid fentanyl, which has caused many accidental deaths in humans. However no human trials of BIMU-8 have yet been carried out.
Other studies have suggested a role for 5HT4 agonists in learning and memory, BIMU-8 was found to increase conditioned responses in mice, and so this drug might also be useful for improving memory in humans. Interestingly other selective 5HT4 agonists such as mosapride (the only
5HT4 agonist currently available for use in humans) have been found not to reduce respiratory depression, suggesting that BIMU-8 may affect 5HT4 receptors in a different way to other 5HT4 agonists, or alternatively that the anti-respiratory depressant effect of BIMU-8 is instead mediated through a different mechanism of action which has not yet been elucidated. | BIMU8
Template:Chembox new
BIMU-8 is a novel compound which acts on an area of the brain stem known as the pre-Botzinger complex.
# Explanation
The pre-Botzinger complex has been found to drive respiration. BIMU-8 stimulates this area of the brain, causing an increase in the rate of respiration. BIMU-8 acts as a selective 5HT4 agonist and is one of the first compounds to be developed that was selective for this serotonin receptor subtype.
# Practical use of BIMU-8
The most obvious practical use of BIMU-8 is to combine it with opiates in order to counteract the dangerous respiratory depressing properties of the latter.[1] BIMU-8 does not affect the painkilling properties of opiates, which means that if combined with BIMU-8, large therapeutic doses of opiates could theoretically be given to humans without risking a decrease in breathing rate. Studies have shown BIMU-8 to be effective in rats at counteracting the respiratory depression caused by the potent opioid fentanyl, which has caused many accidental deaths in humans. However no human trials of BIMU-8 have yet been carried out.
Other studies have suggested a role for 5HT4 agonists in learning and memory,[2] BIMU-8 was found to increase conditioned responses in mice, and so this drug might also be useful for improving memory in humans. Interestingly other selective 5HT4 agonists such as mosapride (the only
5HT4 agonist currently available for use in humans) have been found not to reduce respiratory depression,[3] suggesting that BIMU-8 may affect 5HT4 receptors in a different way to other 5HT4 agonists, or alternatively that the anti-respiratory depressant effect of BIMU-8 is instead mediated through a different mechanism of action which has not yet been elucidated. | https://www.wikidoc.org/index.php/BIMU8 | |
3bcbfadea9a465f05905f87818ee695b8ce2ea41 | wikidoc | BIRC6 | BIRC6
Baculoviral IAP repeat-containing protein 6 is a protein that in humans is encoded by the BIRC6 gene.
# Function
This gene encodes a protein with a BIR (baculoviral inhibition of apoptosis protein repeat) domain and a UBCc (ubiquitin-conjugating enzyme E2, catalytic) domain. This protein inhibits apoptosis by facilitating the degradation of apoptotic proteins by ubiquitination.
# Interactions
BIRC6 has been shown to interact with KIF23.
# Diseases
BIRC6 is implicated in leukemia, melanoma, breast cancer, lung cancer, colorectal cancer, and other cancers (see the Atlas of Genetics and Cytogenetics in Oncology and Haematology). | BIRC6
Baculoviral IAP repeat-containing protein 6 is a protein that in humans is encoded by the BIRC6 gene.[1][2]
# Function
This gene encodes a protein with a BIR (baculoviral inhibition of apoptosis protein repeat) domain and a UBCc (ubiquitin-conjugating enzyme E2, catalytic) domain. This protein inhibits apoptosis by facilitating the degradation of apoptotic proteins by ubiquitination.[2]
# Interactions
BIRC6 has been shown to interact with KIF23.[3]
# Diseases
BIRC6 is implicated in leukemia, melanoma, breast cancer, lung cancer, colorectal cancer, and other cancers[4] (see the Atlas of Genetics and Cytogenetics in Oncology and Haematology[5]). | https://www.wikidoc.org/index.php/BIRC6 | |
2f4e47da7e89e9e58226731f97042da2afd9c9ae | wikidoc | BIRC7 | BIRC7
Baculoviral IAP repeat-containing protein 7 is a protein that in humans is encoded by the BIRC7 gene.
The protein encoded by this gene is a member of the family of inhibitor of apoptosis proteins (IAP) and contains a single copy of a baculovirus IAP repeat (BIR) as well as a RING-type zinc finger domain. The BIR domain is essential for inhibitory activity and interacts with caspases, while the RING finger domain sometimes enhances antiapoptotic activity but does not inhibit apoptosis alone. Two transcript variants encoding different isoforms have been found for this gene. The two isoforms have different antiapoptotic properties, with isoform alpha protecting cells from apoptosis induced by staurosporine and isoform b protecting cells from apoptosis induced by etoposide.
In melanoma, BIRC7 gene expression is regulated by the Microphthalmia-associated transcription factor. | BIRC7
Baculoviral IAP repeat-containing protein 7 is a protein that in humans is encoded by the BIRC7 gene.[1][2][3]
The protein encoded by this gene is a member of the family of inhibitor of apoptosis proteins (IAP) and contains a single copy of a baculovirus IAP repeat (BIR) as well as a RING-type zinc finger domain. The BIR domain is essential for inhibitory activity and interacts with caspases, while the RING finger domain sometimes enhances antiapoptotic activity but does not inhibit apoptosis alone. Two transcript variants encoding different isoforms have been found for this gene. The two isoforms have different antiapoptotic properties, with isoform alpha protecting cells from apoptosis induced by staurosporine and isoform b protecting cells from apoptosis induced by etoposide.[3]
In melanoma, BIRC7 gene expression is regulated by the Microphthalmia-associated transcription factor.[4][5] | https://www.wikidoc.org/index.php/BIRC7 | |
5a4c746c9b7a7ecefa74cbe5b7a8c1b6d5db6254 | wikidoc | BLCAP | BLCAP
Bladder cancer-associated protein is a protein that in humans is encoded by the BLCAP gene.
# Function
BLCAP was identified using a differential display procedure with tumor biopsies obtained from a noninvasive and an invasive bladder transitional cell carcinoma. Although database searches revealed no homology to any human gene at the time of identification, mouse, rat and zebrafish orthologs have since been identified. The protein appears to be down-regulated during bladder cancer progression.
The protein also known as BC10 is an 87-amino-acid-long protein, but its biological functions are largely unknown. However it is a widely believed that the protein is involved in tumour suppression by decreasing cell growth through initiating apoptosis. It is widely expressed protein but expression is particularly high in brain and B lymphocytes. Alternative promoters and alternative splicing allow the protein to exist as several different transcript variants. This number is further increased as the pre-mRNA of this protein is subject to several RNA editing events.
# Structure
The structure of the protein is predicted to be a globular protein with 2 transmembrane (TM) domains.
# RNA editing
The human BLCAP gene is composed of two exons which are separated by an intron. Exon 1 of the gene encodes a 5′ sequence of the 5′UTR while exon 2 includes the remaining sequence of the 5′UTR, the coding region and the 3′UTR. The coding sequence of the BLCAP gene is therefore intronless.
## Type
A to I RNA editing is catalyzed by a family of adenosine deaminases acting on RNA (ADARs) that specifically recognize adenosines within double-stranded regions of pre-mRNAs and deaminate them to inosine. Inosines are recognised as guanosine by the cells translational machinery. There are three members of the ADAR family ADARs 1-3 with ADAR 1 and ADAR 2 being the only enzymatically active members.ADAR3 is thought to have a regulatory role in the brain. ADAR1 and ADAR 2 are widely expressed in tissues while ADAR 3 is restricted to the brain. The double stranded regions of RNA are formed by base-pairing between residues in the close to region of the editing site with residues usually in a neighboring intron but can be an exonic sequence. The region that base pairs with the editing region is known as an Editing Complementary Sequence (ECS).
## Location
The editing sites are all concentrated together between the last 150 nucleotides of intron 1 and the beginning of exon 2. There are 17 identified editing sites in total in the pre-mRNA of this protein. Of these, 11 are found within the intronic sequence (1-11), 3 are in the 5'UTR region (5a,5b,5c) while 3 are found within the coding sequence(Y/C site, Q/R site, K/R site). Some of these editing sites occur in the highly conserved amino terminal of the protein.
The Y/C editing site is located at amino acid 2 of the final protein. The codon change introduces a tyrosine (UAU) to a (UGU) cysteine substitution.
The Q/R site is a second coding region found at amino acid 5 of the final protein. Here the glutamine (Q_) is codon is converted to an arginine (R).
The third K/R editing site within the coding sequence is found at amino acid position 15 of the final protein where a Lysine is converted to an Arginine.
The ECS is predicted to be found in the intron with the double stranded structure formed containing all 17 of the editing sites. It is likely since all the editing sites fall within the duplex region that editing occurs in exonic and intronic sequences at the same time. There is a high level of conservation of the last 150 nucleotides of the intronic region and the start of exon 2.
## Regulation
The BLCAP protein is expressed in a wide range of tissues not just those associated with the nervous system.This indicates that editing may involve ADAR 1 enzyme. However ADAR1 and ADAR2 have been demonstrated to cooperate to edit BLCAP transcript. The pre-mRNA of this protein is edited in many tissues( heart, bladder, lymphocytes, fibroblast, epithelial cells and brain) but the frequency of editing varies in different tissues. There is an overall decrease in BLCAP-editing level in Astrocytomas, Bladder cancer and Colorectal cancer when compared with the relevant normal tissues. HEK 293t cells transfected with either EGFP-ADAR1, EGFP-ADAR2 or untransfected HEK293 cells were used to determine which ADAR enzyme is involved in editing at specific sites in 5'UTR and coding region. The editing level at the Y/C site was 16% while in tumour cells was an average of 21% in brain.It has been shown that ADAR1 does not edit the sites in 5' UTR but ADAR2 edits 5b and 5c sites.Y/c is edited by both and edits the Q/R and K/R sites at higher levels than ADAR1. Low levels of editing are also detected in untransfected vectors. These results indicate that ADAR1 and ADAR2 can edited all sites with ADAR2 being more efficient at the majority of sites.
## Effects
Editing at the Q/R and K/R sites result in positively charge amino acids being placed in the conserved amino terminal of the protein. The three possible editing sites in the coding sequence can result in the translation of up to 8 different protein isoforms. The possible changes to protein function caused by editing is unknown at the current time. | BLCAP
Bladder cancer-associated protein is a protein that in humans is encoded by the BLCAP gene.[1][2]
# Function
BLCAP was identified using a differential display procedure with tumor biopsies obtained from a noninvasive and an invasive bladder transitional cell carcinoma. Although database searches revealed no homology to any human gene at the time of identification, mouse, rat and zebrafish orthologs have since been identified. The protein appears to be down-regulated during bladder cancer progression.[2]
The protein also known as BC10 is an 87-amino-acid-long protein, but its biological functions are largely unknown. However it is a widely believed that the protein is involved in tumour suppression by decreasing cell growth through initiating apoptosis.[3] It is widely expressed protein but expression is particularly high in brain and B lymphocytes.[4] Alternative promoters and alternative splicing allow the protein to exist as several different transcript variants. This number is further increased as the pre-mRNA of this protein is subject to several RNA editing events.[5]
# Structure
The structure of the protein is predicted to be a globular protein with 2 transmembrane (TM) domains.[6]
# RNA editing
The human BLCAP gene is composed of two exons which are separated by an intron. Exon 1 of the gene encodes a 5′ sequence of the 5′UTR while exon 2 includes the remaining sequence of the 5′UTR, the coding region and the 3′UTR. The coding sequence of the BLCAP gene is therefore intronless.[5]
## Type
A to I RNA editing is catalyzed by a family of adenosine deaminases acting on RNA (ADARs) that specifically recognize adenosines within double-stranded regions of pre-mRNAs and deaminate them to inosine. Inosines are recognised as guanosine by the cells translational machinery. There are three members of the ADAR family ADARs 1-3 with ADAR 1 and ADAR 2 being the only enzymatically active members.ADAR3 is thought to have a regulatory role in the brain. ADAR1 and ADAR 2 are widely expressed in tissues while ADAR 3 is restricted to the brain. The double stranded regions of RNA are formed by base-pairing between residues in the close to region of the editing site with residues usually in a neighboring intron but can be an exonic sequence. The region that base pairs with the editing region is known as an Editing Complementary Sequence (ECS).
## Location
The editing sites are all concentrated together between the last 150 nucleotides of intron 1 and the beginning of exon 2. There are 17 identified editing sites in total in the pre-mRNA of this protein. Of these, 11 are found within the intronic sequence (1-11), 3 are in the 5'UTR region (5a,5b,5c) while 3 are found within the coding sequence(Y/C site, Q/R site, K/R site). Some of these editing sites occur in the highly conserved amino terminal of the protein.[7]
The Y/C editing site is located at amino acid 2 of the final protein. The codon change introduces a tyrosine (UAU) to a (UGU) cysteine substitution.[8]
The Q/R site is a second coding region found at amino acid 5 of the final protein. Here the glutamine (Q_) is codon is converted to an arginine (R).[7]
The third K/R editing site within the coding sequence is found at amino acid position 15 of the final protein where a Lysine is converted to an Arginine.[7]
The ECS is predicted to be found in the intron with the double stranded structure formed containing all 17 of the editing sites. It is likely since all the editing sites fall within the duplex region that editing occurs in exonic and intronic sequences at the same time. There is a high level of conservation of the last 150 nucleotides of the intronic region and the start of exon 2.[7]
## Regulation
The BLCAP protein is expressed in a wide range of tissues not just those associated with the nervous system.This indicates that editing may involve ADAR 1 enzyme.[5] However ADAR1 and ADAR2 have been demonstrated to cooperate to edit BLCAP transcript. The pre-mRNA of this protein is edited in many tissues( heart, bladder, lymphocytes, fibroblast, epithelial cells and brain) but the frequency of editing varies in different tissues. There is an overall decrease in BLCAP-editing level in Astrocytomas, Bladder cancer and Colorectal cancer when compared with the relevant normal tissues. HEK 293t cells transfected with either EGFP-ADAR1, EGFP-ADAR2 or untransfected HEK293 cells were used to determine which ADAR enzyme is involved in editing at specific sites in 5'UTR and coding region. The editing level at the Y/C site was 16% while in tumour cells was an average of 21% in brain.It has been shown that ADAR1 does not edit the sites in 5' UTR but ADAR2 edits 5b and 5c sites.Y/c is edited by both and edits the Q/R and K/R sites at higher levels than ADAR1. Low levels of editing are also detected in untransfected vectors. These results indicate that ADAR1 and ADAR2 can edited all sites with ADAR2 being more efficient at the majority of sites.[7]
## Effects
Editing at the Q/R and K/R sites result in positively charge amino acids being placed in the conserved amino terminal of the protein. The three possible editing sites in the coding sequence can result in the translation of up to 8 different protein isoforms.[7] The possible changes to protein function caused by editing is unknown at the current time. | https://www.wikidoc.org/index.php/BLCAP | |
0f092d6e9a3551fa9f6c224a3700b3a092865799 | wikidoc | BMPR2 | BMPR2
Bone morphogenetic protein receptor type II or BMPR2 is a serine/threonine receptor kinase. It binds Bone morphogenetic proteins, members of the TGF beta superfamily of ligands, which are involved in paracrine signalling. BMPs are involved in a host of cellular functions including osteogenesis, cell growth and cell differentiation. Signaling in the BMP pathway begins with the binding of a BMP to the type II receptor. This causes the recruitment of a BMP type I receptor, which it phosphorylates. The Type I receptor phosphorylates an R-SMAD a transcriptional regulator.
# Function
Unlike the TGFβ type II receptor, which has a high affinity for TGF-β1, BMPR2 does not have a high affinity for BMP-2, BMP-7 and BMP-4, unless it is co-expressed with a type I BMP receptor.
On ligand binding, forms a receptor complex consisting of two type II and two type I transmembrane
serine/threonine kinases. Type II receptors phosphorylate and activate type I receptors which autophosphorylate, then
bind and activate SMAD transcriptional regulators. Binds to BMP-7, BMP-2 and, less efficiently, BMP-4. Binding is weak but enhanced by the presence of type I receptors for BMPs. In TGF beta signaling all of the receptors exist in homodimers before ligand binding. In the case of BMP receptors only a small fraction of the receptors exist in homomeric forms before ligand binding. Once a ligand has bound to a receptor, the amount of homomeric receptor oligomers increase, suggesting that the equilibrium shifts towards the homodimeric form. The low affinity for ligands suggests that BMPR2 may differ from other type II TGF beta receptors in that the ligand may bind the type I receptor first.
# Oocyte Development
BMPR2 is expressed on both human and animal granulosa cells, and is a crucial receptor for bone morphogenetic protein 15 (BMP15) and growth differentiation factor 9 (GDF 9). These two protein signaling molecules and their BMPR2 mediated effects play an important role in follicle development in preparation for ovulation. However, BMPR2 can’t bind BMP15 and GDF9 without the assistance of bone morphogenetic protein receptor 1B (BMPR1B) and transforming growth factor β receptor 1 (TGFβR1) respectively. There is evidence that the BMPR2 signaling pathway is disrupted in the case of polycystic ovary syndrome, possibly by hyperaldosterism.
It appears that the hormones estrogen and follicle stimulating hormone (FSH) have roles in regulating expression of BMPR2 in granulosa cells. Experimental treatment in animal models with estradiol with or without FSH increased BMPR2 mRNA expression while treatment with FSH alone decreased BMPR2 expression. However, in human granulosa-like tumor cell line (KGN), treatment with FSH increased BMPR2 expression.
# Clinical significance
An inactivating mutation in the BMPR2 gene has been linked to pulmonary arterial hypertension.
BMPR2 functions to inhibit the proliferation of vascular smooth muscle tissue. It functions by promoting the survival of pulmonary arterial endothelial cells, therefore preventing arterial damage and adverse inflammatory responses. It also inhibits pulmonary arterial proliferation in response to growth factors, which prevents the closing of arteries by proliferating endothelial cells. When this gene is inhibited, vascular smooth muscle proliferates and can cause pulmonary hypertension, which, among other things, can lead to cor pulmonale, a condition that causes the right side of the heart to fail. The dysfunction of BMPR2 can also lead to an elevation in pulmonary arterial pressure due to an adverse response of the pulmonary circuit to injury.
It is especially important to screen for BMPR2 mutations in relatives of patients with idiopathic pulmonary hypertension, for these mutations are present in >70% of familial cases.
There have been studies which has correlated BMPR2 with exercise induced elevation of PA pressure by measuring tricuspid regurgitation velocity by echocardiography. | BMPR2
Bone morphogenetic protein receptor type II or BMPR2 is a serine/threonine receptor kinase. It binds Bone morphogenetic proteins, members of the TGF beta superfamily of ligands, which are involved in paracrine signalling. BMPs are involved in a host of cellular functions including osteogenesis, cell growth and cell differentiation. Signaling in the BMP pathway begins with the binding of a BMP to the type II receptor. This causes the recruitment of a BMP type I receptor, which it phosphorylates. The Type I receptor phosphorylates an R-SMAD a transcriptional regulator.
# Function
Unlike the TGFβ type II receptor, which has a high affinity for TGF-β1, BMPR2 does not have a high affinity for BMP-2, BMP-7 and BMP-4, unless it is co-expressed with a type I BMP receptor.
On ligand binding, forms a receptor complex consisting of two type II and two type I transmembrane
serine/threonine kinases. Type II receptors phosphorylate and activate type I receptors which autophosphorylate, then
bind and activate SMAD transcriptional regulators. Binds to BMP-7, BMP-2 and, less efficiently, BMP-4. Binding is weak but enhanced by the presence of type I receptors for BMPs.[1] In TGF beta signaling all of the receptors exist in homodimers before ligand binding. In the case of BMP receptors only a small fraction of the receptors exist in homomeric forms before ligand binding. Once a ligand has bound to a receptor, the amount of homomeric receptor oligomers increase, suggesting that the equilibrium shifts towards the homodimeric form.[1] The low affinity for ligands suggests that BMPR2 may differ from other type II TGF beta receptors in that the ligand may bind the type I receptor first.[2]
# Oocyte Development
BMPR2 is expressed on both human and animal granulosa cells, and is a crucial receptor for bone morphogenetic protein 15 (BMP15) and growth differentiation factor 9 (GDF 9). These two protein signaling molecules and their BMPR2 mediated effects play an important role in follicle development in preparation for ovulation.[3] However, BMPR2 can’t bind BMP15 and GDF9 without the assistance of bone morphogenetic protein receptor 1B (BMPR1B) and transforming growth factor β receptor 1 (TGFβR1) respectively. There is evidence that the BMPR2 signaling pathway is disrupted in the case of polycystic ovary syndrome, possibly by hyperaldosterism.[4]
It appears that the hormones estrogen and follicle stimulating hormone (FSH) have roles in regulating expression of BMPR2 in granulosa cells. Experimental treatment in animal models with estradiol with or without FSH increased BMPR2 mRNA expression while treatment with FSH alone decreased BMPR2 expression. However, in human granulosa-like tumor cell line (KGN), treatment with FSH increased BMPR2 expression.[5]
# Clinical significance
An inactivating mutation in the BMPR2 gene has been linked to pulmonary arterial hypertension.[6]
BMPR2 functions to inhibit the proliferation of vascular smooth muscle tissue. It functions by promoting the survival of pulmonary arterial endothelial cells, therefore preventing arterial damage and adverse inflammatory responses. It also inhibits pulmonary arterial proliferation in response to growth factors, which prevents the closing of arteries by proliferating endothelial cells.[7] When this gene is inhibited, vascular smooth muscle proliferates and can cause pulmonary hypertension, which, among other things, can lead to cor pulmonale, a condition that causes the right side of the heart to fail. The dysfunction of BMPR2 can also lead to an elevation in pulmonary arterial pressure due to an adverse response of the pulmonary circuit to injury.[7]
It is especially important to screen for BMPR2 mutations in relatives of patients with idiopathic pulmonary hypertension, for these mutations are present in >70% of familial cases.[7]
There have been studies which has correlated BMPR2 with exercise induced elevation of PA pressure by measuring tricuspid regurgitation velocity by echocardiography.[8] | https://www.wikidoc.org/index.php/BMPR2 | |
adb2daa221d0121accbd30a3c057c2dbb5184b0d | wikidoc | BNIP3 | BNIP3
BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 is a protein that in humans is encoded by the BNIP3 gene.
BNIP3 is a member of the apoptotic Bcl-2 protein family that is involved an atypical programmed cell death pathway resembling both necrosis and apoptosis. Many Bcl-2 family proteins modulate the permeability state of the outer mitochondrial membrane by forming homo- and hetero-oligomers. However, sequence similarity with Bcl-2 family members was not detected. Humans and other animals (Drosophila, Caenorhabditis), as well as lower eukaryotes (Dictyostelium, Trypanosoma, Cryptosporidium, Paramecium) encode several BNIP3 paralogues including the human NIP3L, which induces apoptosis by interacting with viral and cellular anti-apoptosis proteins.
# Structure
The right-handed parallel helix-helix structure of the domain with a hydrogen bond-rich His-Ser node in the middle of the membrane, accessibility of the node for water, and continuous hydrophilic track across the membrane suggest that the domain can provide an ion-conducting pathway through the membrane. Incorporation of the BNIP3 transmembrane domain into an artificial lipid bilayer resulted in a pH-dependent conductivity increase. Necrosis-like cell death induced by BNIP3 may be related to this activity.
# Function
BNIP3 interacts with the E1B 19 kDa protein which is responsible for the protection of virally induced cell death, as well as E1B 19 kDa-like sequences of BCL2, also an apoptotic protector. This gene contains a BH3 domain and a transmembrane domain, which have been associated with pro-apoptotic function. The dimeric mitochondrial protein encoded by this gene is known to induce apoptosis, even in the presence of BCL2. Change of BNIP3 expression along other members of the Bcl-2 family measured by qPCR captures important characteristics of malignant transformation, and are defined as markers of resistance toward cell death, a key Cancer Hallmark.
## Transport reaction
The reaction catalyzed by BNIP3 is:
# Interactions
BNIP3 has been shown to interact with CD47, BCL2-like 1 and Bcl-2. | BNIP3
BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 is a protein that in humans is encoded by the BNIP3 gene.[1]
BNIP3 is a member of the apoptotic Bcl-2 protein family that is involved an atypical programmed cell death pathway resembling both necrosis and apoptosis. Many Bcl-2 family proteins modulate the permeability state of the outer mitochondrial membrane by forming homo- and hetero-oligomers. However, sequence similarity with Bcl-2 family members was not detected. Humans and other animals (Drosophila, Caenorhabditis), as well as lower eukaryotes (Dictyostelium, Trypanosoma, Cryptosporidium, Paramecium) encode several BNIP3 paralogues including the human NIP3L, which induces apoptosis by interacting with viral and cellular anti-apoptosis proteins.
# Structure
The right-handed parallel helix-helix structure of the domain with a hydrogen bond-rich His-Ser node in the middle of the membrane, accessibility of the node for water, and continuous hydrophilic track across the membrane suggest that the domain can provide an ion-conducting pathway through the membrane. Incorporation of the BNIP3 transmembrane domain into an artificial lipid bilayer resulted in a pH-dependent conductivity increase. Necrosis-like cell death induced by BNIP3 may be related to this activity.[2]
# Function
BNIP3 interacts with the E1B 19 kDa protein which is responsible for the protection of virally induced cell death, as well as E1B 19 kDa-like sequences of BCL2, also an apoptotic protector. This gene contains a BH3 domain and a transmembrane domain, which have been associated with pro-apoptotic function. The dimeric mitochondrial protein encoded by this gene is known to induce apoptosis, even in the presence of BCL2.[3] Change of BNIP3 expression along other members of the Bcl-2 family measured by qPCR captures important characteristics of malignant transformation, and are defined as markers of resistance toward cell death, a key Cancer Hallmark.[4]
## Transport reaction
The reaction catalyzed by BNIP3 is:
# Interactions
BNIP3 has been shown to interact with CD47,[5] BCL2-like 1[6] and Bcl-2.[1][6] | https://www.wikidoc.org/index.php/BNIP3 | |
37e5928b96e30bb51a08dfa46f376b0d58701345 | wikidoc | BRCA1 | BRCA1
Breast cancer type 1 susceptibility protein is a protein that in humans is encoded by the BRCA1 (/ˌbrækəˈwʌn/) gene. Orthologs are common in other vertebrate species, whereas invertebrate genomes may encode a more distantly related gene. BRCA1 is a human tumor suppressor gene (also known as a caretaker gene) and is responsible for repairing DNA.
BRCA1 and BRCA2 are unrelated proteins, but both are normally expressed in the cells of breast and other tissue, where they help repair damaged DNA, or destroy cells if DNA cannot be repaired. They are involved in the repair of chromosomal damage with an important role in the error-free repair of DNA double-strand breaks. If BRCA1 or BRCA2 itself is damaged by a BRCA mutation, damaged DNA is not repaired properly, and this increases the risk for breast cancer. BRCA1 and BRCA2 have been described as "breast cancer susceptibility genes" and "breast cancer susceptibility proteins". The predominant allele has a normal, tumor suppressive function whereas high penetrance mutations in these genes cause a loss of tumor suppressive function which correlates with an increased risk of breast cancer.
BRCA1 combines with other tumor suppressors, DNA damage sensors and signal transducers to form a large multi-subunit protein complex known as the BRCA1-associated genome surveillance complex (BASC). The BRCA1 protein associates with RNA polymerase II, and through the C-terminal domain, also interacts with histone deacetylase complexes. Thus, this protein plays a role in transcription, and DNA repair of double-strand DNA breaks ubiquitination, transcriptional regulation as well as other functions.
Methods to test for the likelihood of a patient with mutations in BRCA1 and BRCA2 developing cancer were covered by patents owned or controlled by Myriad Genetics. Myriad's business model of offering the diagnostic test exclusively led from Myriad being a startup in 1994 to being a publicly traded company with 1200 employees and about $500M in annual revenue in 2012; it also led to controversy over high prices and the inability to obtain second opinions from other diagnostic labs, which in turn led to the landmark Association for Molecular Pathology v. Myriad Genetics lawsuit.
# Discovery
The first evidence for the existence of a gene encoding a DNA repair enzyme involved in breast cancer susceptibility was provided by Mary-Claire King's laboratory at UC Berkeley in 1990. Four years later, after an international race to find it, the gene was cloned in 1994 by scientists at University of Utah, National Institute of Environmental Health Sciences (NIEHS) and Myriad Genetics.
# Gene location
The human BRCA1 gene is located on the long (q) arm of chromosome 17 at region 2 band 1, from base pair 41,196,312 to base pair 41,277,500 (Build GRCh37/hg19) (map). BRCA1 orthologs have been identified in most vertebrates for which complete genome data are available .
# Protein structure
The BRCA1 protein contains the following domains:
- Zinc finger, C3HC4 type (RING finger)
- BRCA1 C Terminus (BRCT) domain
This protein also contains nuclear localization signals and nuclear export signal motifs.
The human BRCA1 protein consists of four major protein domains; the Znf C3HC4- RING domain, the BRCA1 serine domain and two BRCT domains. These domains encode approximately 27% of BRCA1 protein. There are six known isoforms of BRCA1, with isoforms 1 and 2 comprising 1863 amino acids each.
BRCA1 is unrelated to BRCA2, i.e. they are not homologs or paralogs.
## Zinc ring finger domain
The RING motif, a Zn finger found in eukaryotic peptides, is 40–60 amino acids long and consists of eight conserved metal-binding residues, two quartets of cysteine or histidine residues that coordinate two zinc atoms. This motif contains a short anti-parallel beta-sheet, two zinc-binding loops and a central alpha helix in a small domain. This RING domain interacts with associated proteins, including BARD1, which also contains a RING motif, to form a heterodimer. The BRCA1 RING motif is flanked by alpha helices formed by residues 8–22 and 81–96 of the BRCA1 protein. It interacts with a homologous region in BARD1 also consisting of a RING finger flanked by two alpha-helices formed from residues 36–48 and 101–116. These four helices combine to form a heterodimerization interface and stabilize the BRCA1-BARD1 heterodimer complex. Additional stabilization is achieved by interactions between adjacent residues in the flanking region and hydrophobic interactions. The BARD1/BRCA1 interaction is disrupted by tumorigenic amino acid substitutions in BRCA1, implying that the formation of a stable complex between these proteins may be an essential aspect of BRCA1 tumor suppression.
The ring domain is an important element of ubiquitin E3 ligases, which catalyze protein ubiquitination. Ubiquitin is a small regulatory protein found in all tissues that direct proteins to compartments within the cell. BRCA1 polypeptides, in particular, Lys-48-linked polyubiquitin chains are dispersed throughout the resting cell nucleus, but at the start of DNA replication, they gather in restrained groups that also contain BRCA2 and BARD1. BARD1 is thought to be involved in the recognition and binding of protein targets for ubiquitination. It attaches to proteins and labels them for destruction. Ubiquitination occurs via the BRCA1 fusion protein and is abolished by zinc chelation. The enzyme activity of the fusion protein is dependent on the proper folding of the ring domain.
## Serine cluster domain
BRCA1 serine cluster domain (SCD) spans amino acids 1280–1524. A portion of the domain is located in exons 11–13. High rates of mutation occur in exons 11–13. Reported phosphorylation sites of BRCA1 are concentrated in the SCD, where they are phosphorylated by ATM/ATR kinases both in vitro and in vivo. ATM/ATR are kinases activated by DNA damage. Mutation of serine residues may affect localization of BRCA1 to sites of DNA damage and DNA damage response function.
## BRCT domains
The dual repeat BRCT domain of the BRCA1 protein is an elongated structure approximately 70 Å long and 30–35 Å wide. The 85–95 amino acid domains in BRCT can be found as single modules or as multiple tandem repeats containing two domains. Both of these possibilities can occur in a single protein in a variety of different conformations. The C-terminal BRCT region of the BRCA1 protein is essential for repair of DNA, transcription regulation and tumor suppressor function. In BRCA1 the dual tandem repeat BRCT domains are arranged in a head-to-tail-fashion in the three-dimensional structure, burying 1600 Å of hydrophobic, solvent-accessible surface area in the interface. These all contribute to the tightly packed knob-in-hole structure that comprises the interface. These homologous domains interact to control cellular responses to DNA damage. A missense mutation at the interface of these two proteins can perturb the cell cycle, resulting a greater risk of developing cancer.
# Function and mechanism
BRCA1 is part of a complex that repairs double-strand breaks in DNA. The strands of the DNA double helix are continuously breaking as they become damaged. Sometimes only one strand is broken, sometimes both strands are broken simultaneously. DNA cross-linking agents are an important source of chromosome/DNA damage. Double-strand breaks occur as intermediates after the crosslinks are removed, and indeed, biallelic mutations in BRCA1 have been identified to be responsible for Fanconi Anemia, Complementation Group S, a genetic disease associated with hypersensitivity to DNA crosslinking agents. BRCA1 is part of a protein complex that repairs DNA when both strands are broken. When this happens, it is difficult for the repair mechanism to "know" how to replace the correct DNA sequence, and there are multiple ways to attempt the repair. The double-strand repair mechanism in which BRCA1 participates is homology-directed repair, where the repair proteins copy the identical sequence from the intact sister chromatid.
In the nucleus of many types of normal cells, the BRCA1 protein interacts with RAD51 during repair of DNA double-strand breaks. These breaks can be caused by natural radiation or other exposures, but also occur when chromosomes exchange genetic material (homologous recombination, e.g., "crossing over" during meiosis). The BRCA2 protein, which has a function similar to that of BRCA1, also interacts with the RAD51 protein. By influencing DNA damage repair, these three proteins play a role in maintaining the stability of the human genome.
BRCA1 is also involved in another type of DNA repair, termed mismatch repair. BRCA1 interacts with the DNA mismatch repair protein MSH2. MSH2, MSH6, PARP and some other proteins involved in single-strand repair are reported to be elevated in BRCA1-deficient mammary tumors.
A protein called valosin-containing protein (VCP, also known as p97) plays a role to recruit BRCA1 to the damaged DNA sites. After ionizing radiation, VCP is recruited to DNA lesions and cooperates with the ubiquitin ligase RNF8 to orchestrate assembly of signaling complexes for efficient DSB repair. BRCA1 interacts with VCP. BRCA1 also interacts with c-Myc, and other proteins that are critical to maintain genome stability.
BRCA1 directly binds to DNA, with higher affinity for branched DNA structures. This ability to bind to DNA contributes to its ability to inhibit the nuclease activity of the MRN complex as well as the nuclease activity of Mre11 alone. This may explain a role for BRCA1 to promote lower fidelity DNA repair by non-homologous end joining (NHEJ). BRCA1 also colocalizes with γ-H2AX (histone H2AX phosphorylated on serine-139) in DNA double-strand break repair foci, indicating it may play a role in recruiting repair factors.
Formaldehyde and acetaldehyde are common environmental sources of DNA cross links that often require repairs mediated by BRCA1 containing pathways.
This DNA repair function is essential; mice with loss-of-function mutations in both BRCA1 alleles are not viable, and as of 2015 only two adults were known to have loss-of-function mutations in both alleles; both had congenital or developmental issues, and both had cancer. One was presumed to have survived to adulthood because one of the BRCA1 mutations was hypomorphic.
## Transcription
BRCA1 was shown to co-purify with the human RNA Polymerase II holoenzyme in HeLa extracts, implying it is a component of the holoenzyme. Later research, however, contradicted this assumption, instead showing that the predominant complex including BRCA1 in HeLa cells is a 2 megadalton complex containing SWI/SNF. SWI/SNF is a chromatin remodeling complex. Artificial tethering of BRCA1 to chromatin was shown to decondense heterochromatin, though the SWI/SNF interacting domain was not necessary for this role. BRCA1 interacts with the NELF-B (COBRA1) subunit of the NELF complex.
# Mutations and cancer risk
Certain variations of the BRCA1 gene lead to an increased risk for breast cancer as part of a hereditary breast-ovarian cancer syndrome. Researchers have identified hundreds of mutations in the BRCA1 gene, many of which are associated with an increased risk of cancer. Females with an abnormal BRCA1 or BRCA2 gene have up to an 80% risk of developing breast cancer by age 90; increased risk of developing ovarian cancer is about 55% for females with BRCA1 mutations and about 25% for females with BRCA2 mutations.
These mutations can be changes in one or a small number of DNA base pairs (the building-blocks of DNA), and can be identified with PCR and DNA sequencing.
In some cases, large segments of DNA are rearranged. Those large segments, also called large rearrangements, can be a deletion or a duplication of one or several exons in the gene. Classical methods for mutation detection (sequencing) are unable to reveal these types of mutation. Other methods have been proposed: traditional quantitative PCR, Multiplex Ligation-dependent Probe Amplification (MLPA), and Quantitative Multiplex PCR of Short Fluorescent Fragments (QMPSF). Newer methods have also been recently proposed: heteroduplex analysis (HDA) by multi-capillary electrophoresis or also dedicated oligonucleotides array based on comparative genomic hybridization (array-CGH).
Some results suggest that hypermethylation of the BRCA1 promoter, which has been reported in some cancers, could be considered as an inactivating mechanism for BRCA1 expression.
A mutated BRCA1 gene usually makes a protein that does not function properly. Researchers believe that the defective BRCA1 protein is unable to help fix DNA damage leading to mutations in other genes. These mutations can accumulate and may allow cells to grow and divide uncontrollably to form a tumor. Thus, BRCA1 inactivating mutations lead to a predisposition for cancer.
BRCA1 mRNA 3' UTR can be bound by an miRNA, Mir-17 microRNA. It has been suggested that variations in this miRNA along with Mir-30 microRNA could confer susceptibility to breast cancer.
In addition to breast cancer, mutations in the BRCA1 gene also increase the risk of ovarian and prostate cancers. Moreover, precancerous lesions (dysplasia) within the Fallopian tube have been linked to BRCA1 gene mutations. Pathogenic mutations anywhere in a model pathway containing BRCA1 and BRCA2 greatly increase risks for a subset of leukemias and lymphomas.
Females who have inherited a defective BRCA1 or BRCA2 gene are at a greatly elevated risk to develop breast and ovarian cancer. Their risk of developing breast and/or ovarian cancer is so high, and so specific to those cancers, that many mutation carriers choose to have prophylactic surgery. There has been much conjecture to explain such apparently striking tissue specificity. Major determinants of where BRCA1/2 hereditary cancers occur are related to tissue specificity of the cancer pathogen, the agent that causes chronic inflammation or the carcinogen. The target tissue may have receptors for the pathogen, may become selectively exposed to an inflammatory process or to a carcinogen. An innate genomic deficit in a tumor suppressor gene impairs normal responses and exacerbates the susceptibility to disease in organ targets. This theory also fits data for several tumor suppressors beyond BRCA1 or BRCA2. A major advantage of this model is that it suggests there may be some options in addition to prophylactic surgery.
# Low expression of BRCA1 in breast and ovarian cancers
BRCA1 expression is reduced or undetectable in the majority of high grade, ductal breast cancers. It has long been noted that loss of BRCA1 activity, either by germ-line mutations or by down-regulation of gene expression, leads to tumor formation in specific target tissues. In particular, decreased BRCA1 expression contributes to both sporadic and inherited breast tumor progression. Reduced expression of BRCA1 is tumorigenic because it plays an important role in the repair of DNA damages, especially double-strand breaks, by the potentially error-free pathway of homologous recombination. Since cells that lack the BRCA1 protein tend to repair DNA damages by alternative more error-prone mechanisms, the reduction or silencing of this protein generates mutations and gross chromosomal rearrangements that can lead to progression to breast cancer.
Similarly, BRCA1 expression is low in the majority (55%) of sporadic epithelial ovarian cancers (EOCs) where EOCs are the most common type of ovarian cancer, representing approximately 90% of ovarian cancers. In serous ovarian carcinomas, a sub-category constituting about 2/3 of EOCs, low BRCA1 expression occurs in more than 50% of cases. Bowtell reviewed the literature indicating that deficient homologous recombination repair caused by BRCA1 deficiency is tumorigenic. In particular this deficiency initiates a cascade of molecular events that sculpt the evolution of high-grade serous ovarian cancer and dictate its response to therapy. Especially noted was that BRCA1 deficiency could be the cause of tumorigenesis whether due to BRCA1 mutation or any other event that causes a deficiency of BRCA1 expression.
## Mutation of BRCA1 in breast and ovarian cancer
Only about 3%–8% of all women with breast cancer carry a mutation in BRCA1 or BRCA2. Similarly, BRCA1 mutations are only seen in about 18% of ovarian cancers (13% germline mutations and 5% somatic mutations).
Thus, while BRCA1 expression is low in the majority of these cancers, BRCA1 mutation is not a major cause of reduced expression.
## BRCA1 promoter hypermethylation in breast and ovarian cancer
BRCA1 promoter hypermethylation was present in only 13% of unselected primary breast carcinomas. Similarly, BRCA1 promoter hypermethylation was present in only 5% to 15% of EOC cases.
Thus, while BRCA1 expression is low in these cancers, BRCA1 promoter methylation is only a minor cause of reduced expression.
## MicroRNA repression of BRCA1 in breast cancers
There are a number of specific microRNAs, when overexpressed, that directly reduce expression of specific DNA repair proteins (see MicroRNA section DNA repair and cancer) In the case of breast cancer, microRNA-182 (miR-182) specifically targets BRCA1. Breast cancers can be classified based on receptor status or histology, with triple-negative breast cancer (15%–25% of breast cancers), HER2+ (15%–30% of breast cancers), ER+/PR+ (about 70% of breast cancers), and Invasive lobular carcinoma (about 5%–10% of invasive breast cancer). All four types of breast cancer were found to have an average of about 100-fold increase in miR-182, compared to normal breast tissue. In breast cancer cell lines, there is an inverse correlation of BRCA1 protein levels with miR-182 expression. Thus it appears that much of the reduction or absence of BRCA1 in high grade ductal breast cancers may be due to over-expressed miR-182.
In addition to miR-182, a pair of almost identical microRNAs, miR-146a and miR-146b-5p, also repress BRCA1 expression. These two microRNAs are over-expressed in triple-negative tumors and their over-expression results in BRCA1 inactivation. Thus, miR-146a and/or miR-146b-5p may also contribute to reduced expression of BRCA1 in these triple-negative breast cancers.
## MicroRNA repression of BRCA1 in ovarian cancers
In both serous tubal intraepithelial carcinoma (the precursor lesion to high grade serous ovarian carcinoma (HG-SOC)), and in HG-SOC itself, miR-182 is overexpressed in about 70% of cases. In cells with over-expressed miR-182, BRCA1 remained low, even after exposure to ionizing radiation (which normally raises BRCA1 expression). Thus much of the reduced or absent BRCA1 in HG-SOC may be due to over-expressed miR-182.
Another microRNA known to reduce expression of BRCA1 in ovarian cancer cells is miR-9. Among 58 tumors from patients with stage IIIC or stage IV serous ovarian cancers (HG-SOG), an inverse correlation was found between expressions of miR-9 and BRCA1, so that increased miR-9 may also contribute to reduced expression of BRCA1 in these ovarian cancers.
## Deficiency of BRCA1 expression is likely tumorigenic
DNA damage appears to be the primary underlying cause of cancer, and deficiencies in DNA repair appears to underlie many forms of cancer. If DNA repair is deficient, DNA damage tends to accumulate. Such excess DNA damage may increase mutational errors during DNA replication due to error-prone translesion synthesis. Excess DNA damage may also increase epigenetic alterations due to errors during DNA repair. Such mutations and epigenetic alterations may give rise to cancer. The frequent microRNA-induced deficiency of BRCA1 in breast and ovarian cancers likely contribute to the progression of those cancers.
# Germ line mutations and founder effect
All germ-line BRCA1 mutations identified to date have been inherited, suggesting the possibility of a large “founder” effect in which a certain mutation is common to a well-defined population group and can, in theory, be traced back to a common ancestor. Given the complexity of mutation screening for BRCA1, these common mutations may simplify the methods required for mutation screening in certain populations. Analysis of mutations that occur with high frequency also permits the study of their clinical expression. Examples of manifestations of a founder effect are seen among Ashkenazi Jews. Three mutations in BRCA1 have been reported to account for the majority of Ashkenazi Jewish patients with inherited BRCA1-related breast and/or ovarian cancer: 185delAG, 188del11 and 5382insC in the BRCA1 gene. In fact, it has been shown that if a Jewish woman does not carry a BRCA1 185delAG, BRCA1 5382insC founder mutation, it is highly unlikely that a different BRCA1 mutation will be found. Additional examples of founder mutations in BRCA1 are given in Table 1 (mainly derived from ).
# Female fertility
As women age, reproductive performance declines, leading to menopause. This decline is tied to a reduction in the number of ovarian follicles. Although about 1 million oocytes are present at birth in the human ovary, only about 500 (about 0.05%) of these ovulate. The decline in ovarian reserve appears to occur at a constantly increasing rate with age, and leads to nearly complete exhaustion of the reserve by about age 52. As ovarian reserve and fertility decline with age, there is also a parallel increase in pregnancy failure and meiotic errors, resulting in chromosomally abnormal conceptions.
Women with a germ-line BRCA1 mutation appear to have a diminished oocyte reserve and decreased fertility compared to normally aging women. Furthermore, women with an inherited BRCA1 mutation undergo menopause prematurely. Since BRCA1 is a key DNA repair protein, these findings suggest that naturally occurring DNA damages in oocytes are repaired less efficiently in women with a BRCA1 defect, and that this repair inefficiency leads to early reproductive failure.
As noted above, the BRCA1 protein plays a key role in homologous recombinational repair. This is the only known cellular process that can accurately repair DNA double-strand breaks. DNA double-strand breaks accumulate with age in humans and mice in primordial follicles. Primordial follicles contain oocytes that are at an intermediate (prophase I) stage of meiosis. Meiosis is the general process in eukaryotic organisms by which germ cells are formed, and it is likely an adaptation for removing DNA damages, especially double-strand breaks, from germ line DNA. (Also see article Meiosis). Homologous recombinational repair employing BRCA1 is especially promoted during meiosis. It was found that expression of 4 key genes necessary for homologous recombinational repair of DNA double-strand breaks (BRCA1, MRE11, RAD51 and ATM) decline with age in the oocytes of humans and mice, leading to the hypothesis that DNA double-strand break repair is necessary for the maintenance of oocyte reserve and that a decline in efficiency of repair with age plays a role in ovarian aging.
# Cancer chemotherapy
Non-small cell lung cancer (NSCLC) is the leading cause of cancer deaths worldwide. At diagnosis, almost 70% of persons with NSCLC have locally advanced or metastatic disease. Persons with NSCLC are often treated with therapeutic platinum compounds (e.g. cisplatin, carboplatin or oxaliplatin) that cause inter-strand cross-links in DNA. Among individuals with NSCLC, low expression of BRCA1 in the primary tumor correlated with improved survival after platinum-containing chemotherapy. This correlation implies that low BRCA1 in cancer, and the consequent low level of DNA repair, causes vulnerability of cancer to treatment by the DNA cross-linking agents. High BRCA1 may protect cancer cells by acting in a pathway that removes the damages in DNA introduced by the platinum drugs. Thus the level of BRCA1 expression is a potentially important tool for tailoring chemotherapy in lung cancer management.
Level of BRCA1 expression is also relevant to ovarian cancer treatment. Patients having sporadic ovarian cancer who were treated with platinum drugs had longer median survival times if their BRCA1 expression was low compared to patients with higher BRCA1 expression (46 compared to 33 months).
# Patents, enforcement, litigation, and controversy
A patent application for the isolated BRCA1 gene and cancer promoting mutations discussed above, as well as methods to diagnose the likelihood of getting breast cancer, was filed by the University of Utah, National Institute of Environmental Health Sciences (NIEHS) and Myriad Genetics in 1994; over the next year, Myriad, (in collaboration with investigators at Endo Recherche, Inc., HSC Research & Development Limited Partnership, and University of Pennsylvania), isolated and sequenced the BRCA2 gene and identified key mutations, and the first BRCA2 patent was filed in the U.S. by Myriad and other institutions in 1995. Myriad is the exclusive licensee of these patents and has enforced them in the US against clinical diagnostic labs. This business model led from Myriad being a startup in 1994 to being a publicly traded company with 1200 employees and about $500M in annual revenue in 2012; it also led to controversy over high prices and the inability to get second opinions from other diagnostic labs, which in turn led to the landmark Association for Molecular Pathology v. Myriad Genetics lawsuit. The patents began to expire in 2014.
According to an article published in the journal, Genetic Medicine, in 2010, "The patent story outside the United States is more complicated.... For example, patents have been obtained but the patents are being ignored by provincial health systems in Canada. In Australia and the UK, Myriad’s licensee permitted use by health systems but announced a change of plans in August 2008. Only a single mutation has been patented in Myriad’s lone European-wide patent, although some patents remain under review of an opposition proceeding. In effect, the United States is the only jurisdiction where Myriad’s strong patent position has conferred sole-provider status." Peter Meldrum, CEO of Myriad Genetics, has acknowledged that Myriad has "other competitive advantages that may make such enforcement unnecessary" in Europe.
As with any gene, finding variation in BRCA1 is not hard. The real value comes from understanding what the clinical consequences of any particular variant are. Myriad has a large, proprietary database of such genotype-phenotype correlations. In response, parallel open-source databases are being developed.
Legal decisions surrounding the BRCA1 and BRCA2 patents will affect the field of genetic testing in general. A June 2013 article, in Association for Molecular Pathology v. Myriad Genetics (No. 12-398), quoted the US Supreme Court's unanimous ruling that, "A naturally occurring DNA segment is a product of nature and not patent eligible merely because it has been isolated," invalidating Myriad's patents on the BRCA1 and BRCA2 genes. However, the Court also held that manipulation of a gene to create something not found in nature could still be eligible for patent protection. The Federal Court of Australia came to the opposite conclusion, upholding the validity of an Australian Myriad Genetics patent over the BRCA1 gene in February 2013. The Federal Court also rejected an appeal in September 2014. Yvonne D’Arcy won her case against US-based biotech company Myriad Genetics in the High Court of Australia. In their unanimous decision on October 7, 2015 the "high court found that an isolated nucleic acid, coding for a BRCA1 protein, with specific variations from the norm that are indicative of susceptibility to breast cancer and ovarian cancer was not a 'patentable invention.'"
# Interactions
BRCA1 has been shown to interact with the following proteins:
- ABL1,
- AKT1,
- AR,
- ATR,
- ATM,
- ATF1,
- AURKA,
- BACH1,
- BARD1,
- BRCA2,
- BRCC3,
- BRE,
- BRIP1,
- C-jun,
- CHEK2,
- CLSPN,
- COBRA1,
- CREBBP,
- CSNK2B,
- CSTF2,
- CDK2,
- DHX9,
- ELK4,
- EP300,
- ESR1,
- FANCA,
- FANCD2,
- FHL2,
- H2AFX,
- JUNB,
- JunD,
- LMO4,
- MAP3K3,
- MED1,
- MED17,
- MED21,
- MED24,
- MRE11A,
- MSH2,
- MSH3,
- MSH6,
- Myc,
- NBN,
- NMI,
- NPM1,
- NCOA2,
- NUFIP1,
- P53,
- PALB2,
- POLR2A,
- PPP1CA,
- Rad50,
- RAD51,
- RBBP4,
- RBBP7,
- RBBP8,
- RELA,
- RB1,
- RBL1,
- RBL2,
- RPL31,
- SMARCA4,
- SMARCB1,
- STAT1,
- UBE2D1,
- USF2,
- VCP,
- XIST, and
- ZNF350. | BRCA1
Breast cancer type 1 susceptibility protein is a protein that in humans is encoded by the BRCA1 (/ˌbrækəˈwʌn/) gene.[1] Orthologs are common in other vertebrate species, whereas invertebrate genomes may encode a more distantly related gene.[2] BRCA1 is a human tumor suppressor gene[3][4] (also known as a caretaker gene) and is responsible for repairing DNA.[5]
BRCA1 and BRCA2 are unrelated proteins,[6] but both are normally expressed in the cells of breast and other tissue, where they help repair damaged DNA, or destroy cells if DNA cannot be repaired. They are involved in the repair of chromosomal damage with an important role in the error-free repair of DNA double-strand breaks.[7][8] If BRCA1 or BRCA2 itself is damaged by a BRCA mutation, damaged DNA is not repaired properly, and this increases the risk for breast cancer.[9][10] BRCA1 and BRCA2 have been described as "breast cancer susceptibility genes" and "breast cancer susceptibility proteins". The predominant allele has a normal, tumor suppressive function whereas high penetrance mutations in these genes cause a loss of tumor suppressive function which correlates with an increased risk of breast cancer.[11]
BRCA1 combines with other tumor suppressors, DNA damage sensors and signal transducers to form a large multi-subunit protein complex known as the BRCA1-associated genome surveillance complex (BASC).[12] The BRCA1 protein associates with RNA polymerase II, and through the C-terminal domain, also interacts with histone deacetylase complexes. Thus, this protein plays a role in transcription, and DNA repair of double-strand DNA breaks[10] ubiquitination, transcriptional regulation as well as other functions.[13]
Methods to test for the likelihood of a patient with mutations in BRCA1 and BRCA2 developing cancer were covered by patents owned or controlled by Myriad Genetics.[14][15] Myriad's business model of offering the diagnostic test exclusively led from Myriad being a startup in 1994 to being a publicly traded company with 1200 employees and about $500M in annual revenue in 2012;[16] it also led to controversy over high prices and the inability to obtain second opinions from other diagnostic labs, which in turn led to the landmark Association for Molecular Pathology v. Myriad Genetics lawsuit.[17]
# Discovery
The first evidence for the existence of a gene encoding a DNA repair enzyme involved in breast cancer susceptibility was provided by Mary-Claire King's laboratory at UC Berkeley in 1990.[18] Four years later, after an international race to find it,[19] the gene was cloned in 1994 by scientists at University of Utah, National Institute of Environmental Health Sciences (NIEHS) and Myriad Genetics.[14][20]
# Gene location
The human BRCA1 gene is located on the long (q) arm of chromosome 17 at region 2 band 1, from base pair 41,196,312 to base pair 41,277,500 (Build GRCh37/hg19) (map).[21] BRCA1 orthologs have been identified in most vertebrates for which complete genome data are available [2].
# Protein structure
The BRCA1 protein contains the following domains:[22]
- Zinc finger, C3HC4 type (RING finger)
- BRCA1 C Terminus (BRCT) domain
This protein also contains nuclear localization signals and nuclear export signal motifs.[23]
The human BRCA1 protein consists of four major protein domains; the Znf C3HC4- RING domain, the BRCA1 serine domain and two BRCT domains. These domains encode approximately 27% of BRCA1 protein. There are six known isoforms of BRCA1,[24] with isoforms 1 and 2 comprising 1863 amino acids each.[citation needed]
BRCA1 is unrelated to BRCA2, i.e. they are not homologs or paralogs.[6]
## Zinc ring finger domain
The RING motif, a Zn finger found in eukaryotic peptides, is 40–60 amino acids long and consists of eight conserved metal-binding residues, two quartets of cysteine or histidine residues that coordinate two zinc atoms.[26] This motif contains a short anti-parallel beta-sheet, two zinc-binding loops and a central alpha helix in a small domain. This RING domain interacts with associated proteins, including BARD1, which also contains a RING motif, to form a heterodimer. The BRCA1 RING motif is flanked by alpha helices formed by residues 8–22 and 81–96 of the BRCA1 protein. It interacts with a homologous region in BARD1 also consisting of a RING finger flanked by two alpha-helices formed from residues 36–48 and 101–116. These four helices combine to form a heterodimerization interface and stabilize the BRCA1-BARD1 heterodimer complex. Additional stabilization is achieved by interactions between adjacent residues in the flanking region and hydrophobic interactions. The BARD1/BRCA1 interaction is disrupted by tumorigenic amino acid substitutions in BRCA1, implying that the formation of a stable complex between these proteins may be an essential aspect of BRCA1 tumor suppression.[26]
The ring domain is an important element of ubiquitin E3 ligases, which catalyze protein ubiquitination. Ubiquitin is a small regulatory protein found in all tissues that direct proteins to compartments within the cell. BRCA1 polypeptides, in particular, Lys-48-linked polyubiquitin chains are dispersed throughout the resting cell nucleus, but at the start of DNA replication, they gather in restrained groups that also contain BRCA2 and BARD1. BARD1 is thought to be involved in the recognition and binding of protein targets for ubiquitination.[27] It attaches to proteins and labels them for destruction. Ubiquitination occurs via the BRCA1 fusion protein and is abolished by zinc chelation.[26] The enzyme activity of the fusion protein is dependent on the proper folding of the ring domain.[citation needed]
## Serine cluster domain
BRCA1 serine cluster domain (SCD) spans amino acids 1280–1524. A portion of the domain is located in exons 11–13. High rates of mutation occur in exons 11–13. Reported phosphorylation sites of BRCA1 are concentrated in the SCD, where they are phosphorylated by ATM/ATR kinases both in vitro and in vivo. ATM/ATR are kinases activated by DNA damage. Mutation of serine residues may affect localization of BRCA1 to sites of DNA damage and DNA damage response function.[25][28]
## BRCT domains
The dual repeat BRCT domain of the BRCA1 protein is an elongated structure approximately 70 Å long and 30–35 Å wide.[29] The 85–95 amino acid domains in BRCT can be found as single modules or as multiple tandem repeats containing two domains.[30] Both of these possibilities can occur in a single protein in a variety of different conformations.[29] The C-terminal BRCT region of the BRCA1 protein is essential for repair of DNA, transcription regulation and tumor suppressor function.[31] In BRCA1 the dual tandem repeat BRCT domains are arranged in a head-to-tail-fashion in the three-dimensional structure, burying 1600 Å of hydrophobic, solvent-accessible surface area in the interface. These all contribute to the tightly packed knob-in-hole structure that comprises the interface. These homologous domains interact to control cellular responses to DNA damage. A missense mutation at the interface of these two proteins can perturb the cell cycle, resulting a greater risk of developing cancer.
# Function and mechanism
BRCA1 is part of a complex that repairs double-strand breaks in DNA. The strands of the DNA double helix are continuously breaking as they become damaged. Sometimes only one strand is broken, sometimes both strands are broken simultaneously. DNA cross-linking agents are an important source of chromosome/DNA damage. Double-strand breaks occur as intermediates after the crosslinks are removed, and indeed, biallelic mutations in BRCA1 have been identified to be responsible for Fanconi Anemia, Complementation Group S,[32] a genetic disease associated with hypersensitivity to DNA crosslinking agents. BRCA1 is part of a protein complex that repairs DNA when both strands are broken. When this happens, it is difficult for the repair mechanism to "know" how to replace the correct DNA sequence, and there are multiple ways to attempt the repair. The double-strand repair mechanism in which BRCA1 participates is homology-directed repair, where the repair proteins copy the identical sequence from the intact sister chromatid.[33]
In the nucleus of many types of normal cells, the BRCA1 protein interacts with RAD51 during repair of DNA double-strand breaks.[34] These breaks can be caused by natural radiation or other exposures, but also occur when chromosomes exchange genetic material (homologous recombination, e.g., "crossing over" during meiosis). The BRCA2 protein, which has a function similar to that of BRCA1, also interacts with the RAD51 protein. By influencing DNA damage repair, these three proteins play a role in maintaining the stability of the human genome.[citation needed]
BRCA1 is also involved in another type of DNA repair, termed mismatch repair. BRCA1 interacts with the DNA mismatch repair protein MSH2.[35] MSH2, MSH6, PARP and some other proteins involved in single-strand repair are reported to be elevated in BRCA1-deficient mammary tumors.[36]
A protein called valosin-containing protein (VCP, also known as p97) plays a role to recruit BRCA1 to the damaged DNA sites. After ionizing radiation, VCP is recruited to DNA lesions and cooperates with the ubiquitin ligase RNF8 to orchestrate assembly of signaling complexes for efficient DSB repair.[37] BRCA1 interacts with VCP.[38] BRCA1 also interacts with c-Myc, and other proteins that are critical to maintain genome stability.[39]
BRCA1 directly binds to DNA, with higher affinity for branched DNA structures. This ability to bind to DNA contributes to its ability to inhibit the nuclease activity of the MRN complex as well as the nuclease activity of Mre11 alone.[40] This may explain a role for BRCA1 to promote lower fidelity DNA repair by non-homologous end joining (NHEJ).[41] BRCA1 also colocalizes with γ-H2AX (histone H2AX phosphorylated on serine-139) in DNA double-strand break repair foci, indicating it may play a role in recruiting repair factors.[13][42]
Formaldehyde and acetaldehyde are common environmental sources of DNA cross links that often require repairs mediated by BRCA1 containing pathways.[43][44]
This DNA repair function is essential; mice with loss-of-function mutations in both BRCA1 alleles are not viable, and as of 2015 only two adults were known to have loss-of-function mutations in both alleles; both had congenital or developmental issues, and both had cancer. One was presumed to have survived to adulthood because one of the BRCA1 mutations was hypomorphic.[45]
## Transcription
BRCA1 was shown to co-purify with the human RNA Polymerase II holoenzyme in HeLa extracts, implying it is a component of the holoenzyme.[46] Later research, however, contradicted this assumption, instead showing that the predominant complex including BRCA1 in HeLa cells is a 2 megadalton complex containing SWI/SNF.[47] SWI/SNF is a chromatin remodeling complex. Artificial tethering of BRCA1 to chromatin was shown to decondense heterochromatin, though the SWI/SNF interacting domain was not necessary for this role.[42] BRCA1 interacts with the NELF-B (COBRA1) subunit of the NELF complex.[42]
# Mutations and cancer risk
Certain variations of the BRCA1 gene lead to an increased risk for breast cancer as part of a hereditary breast-ovarian cancer syndrome. Researchers have identified hundreds of mutations in the BRCA1 gene, many of which are associated with an increased risk of cancer. Females with an abnormal BRCA1 or BRCA2 gene have up to an 80% risk of developing breast cancer by age 90; increased risk of developing ovarian cancer is about 55% for females with BRCA1 mutations and about 25% for females with BRCA2 mutations.[48]
These mutations can be changes in one or a small number of DNA base pairs (the building-blocks of DNA), and can be identified with PCR and DNA sequencing.[citation needed]
In some cases, large segments of DNA are rearranged. Those large segments, also called large rearrangements, can be a deletion or a duplication of one or several exons in the gene. Classical methods for mutation detection (sequencing) are unable to reveal these types of mutation.[49] Other methods have been proposed: traditional quantitative PCR,[50] Multiplex Ligation-dependent Probe Amplification (MLPA),[51] and Quantitative Multiplex PCR of Short Fluorescent Fragments (QMPSF).[52] Newer methods have also been recently proposed: heteroduplex analysis (HDA) by multi-capillary electrophoresis or also dedicated oligonucleotides array based on comparative genomic hybridization (array-CGH).[53]
Some results suggest that hypermethylation of the BRCA1 promoter, which has been reported in some cancers, could be considered as an inactivating mechanism for BRCA1 expression.[54]
A mutated BRCA1 gene usually makes a protein that does not function properly. Researchers believe that the defective BRCA1 protein is unable to help fix DNA damage leading to mutations in other genes. These mutations can accumulate and may allow cells to grow and divide uncontrollably to form a tumor. Thus, BRCA1 inactivating mutations lead to a predisposition for cancer.[citation needed]
BRCA1 mRNA 3' UTR can be bound by an miRNA, Mir-17 microRNA. It has been suggested that variations in this miRNA along with Mir-30 microRNA could confer susceptibility to breast cancer.[55]
In addition to breast cancer, mutations in the BRCA1 gene also increase the risk of ovarian and prostate cancers. Moreover, precancerous lesions (dysplasia) within the Fallopian tube have been linked to BRCA1 gene mutations. Pathogenic mutations anywhere in a model pathway containing BRCA1 and BRCA2 greatly increase risks for a subset of leukemias and lymphomas.[10]
Females who have inherited a defective BRCA1 or BRCA2 gene are at a greatly elevated risk to develop breast and ovarian cancer. Their risk of developing breast and/or ovarian cancer is so high, and so specific to those cancers, that many mutation carriers choose to have prophylactic surgery. There has been much conjecture to explain such apparently striking tissue specificity. Major determinants of where BRCA1/2 hereditary cancers occur are related to tissue specificity of the cancer pathogen, the agent that causes chronic inflammation or the carcinogen. The target tissue may have receptors for the pathogen, may become selectively exposed to an inflammatory process or to a carcinogen. An innate genomic deficit in a tumor suppressor gene impairs normal responses and exacerbates the susceptibility to disease in organ targets. This theory also fits data for several tumor suppressors beyond BRCA1 or BRCA2. A major advantage of this model is that it suggests there may be some options in addition to prophylactic surgery.[56]
# Low expression of BRCA1 in breast and ovarian cancers
BRCA1 expression is reduced or undetectable in the majority of high grade, ductal breast cancers.[57] It has long been noted that loss of BRCA1 activity, either by germ-line mutations or by down-regulation of gene expression, leads to tumor formation in specific target tissues. In particular, decreased BRCA1 expression contributes to both sporadic and inherited breast tumor progression.[58] Reduced expression of BRCA1 is tumorigenic because it plays an important role in the repair of DNA damages, especially double-strand breaks, by the potentially error-free pathway of homologous recombination.[59] Since cells that lack the BRCA1 protein tend to repair DNA damages by alternative more error-prone mechanisms, the reduction or silencing of this protein generates mutations and gross chromosomal rearrangements that can lead to progression to breast cancer.[59]
Similarly, BRCA1 expression is low in the majority (55%) of sporadic epithelial ovarian cancers (EOCs) where EOCs are the most common type of ovarian cancer, representing approximately 90% of ovarian cancers.[60] In serous ovarian carcinomas, a sub-category constituting about 2/3 of EOCs, low BRCA1 expression occurs in more than 50% of cases.[61] Bowtell[62] reviewed the literature indicating that deficient homologous recombination repair caused by BRCA1 deficiency is tumorigenic. In particular this deficiency initiates a cascade of molecular events that sculpt the evolution of high-grade serous ovarian cancer and dictate its response to therapy. Especially noted was that BRCA1 deficiency could be the cause of tumorigenesis whether due to BRCA1 mutation or any other event that causes a deficiency of BRCA1 expression.
## Mutation of BRCA1 in breast and ovarian cancer
Only about 3%–8% of all women with breast cancer carry a mutation in BRCA1 or BRCA2.[63] Similarly, BRCA1 mutations are only seen in about 18% of ovarian cancers (13% germline mutations and 5% somatic mutations).[64]
Thus, while BRCA1 expression is low in the majority of these cancers, BRCA1 mutation is not a major cause of reduced expression.
## BRCA1 promoter hypermethylation in breast and ovarian cancer
BRCA1 promoter hypermethylation was present in only 13% of unselected primary breast carcinomas.[65] Similarly, BRCA1 promoter hypermethylation was present in only 5% to 15% of EOC cases.[60]
Thus, while BRCA1 expression is low in these cancers, BRCA1 promoter methylation is only a minor cause of reduced expression.
## MicroRNA repression of BRCA1 in breast cancers
There are a number of specific microRNAs, when overexpressed, that directly reduce expression of specific DNA repair proteins (see MicroRNA section DNA repair and cancer) In the case of breast cancer, microRNA-182 (miR-182) specifically targets BRCA1.[66] Breast cancers can be classified based on receptor status or histology, with triple-negative breast cancer (15%–25% of breast cancers), HER2+ (15%–30% of breast cancers), ER+/PR+ (about 70% of breast cancers), and Invasive lobular carcinoma (about 5%–10% of invasive breast cancer). All four types of breast cancer were found to have an average of about 100-fold increase in miR-182, compared to normal breast tissue.[67] In breast cancer cell lines, there is an inverse correlation of BRCA1 protein levels with miR-182 expression.[66] Thus it appears that much of the reduction or absence of BRCA1 in high grade ductal breast cancers may be due to over-expressed miR-182.
In addition to miR-182, a pair of almost identical microRNAs, miR-146a and miR-146b-5p, also repress BRCA1 expression. These two microRNAs are over-expressed in triple-negative tumors and their over-expression results in BRCA1 inactivation.[68] Thus, miR-146a and/or miR-146b-5p may also contribute to reduced expression of BRCA1 in these triple-negative breast cancers.
## MicroRNA repression of BRCA1 in ovarian cancers
In both serous tubal intraepithelial carcinoma (the precursor lesion to high grade serous ovarian carcinoma (HG-SOC)), and in HG-SOC itself, miR-182 is overexpressed in about 70% of cases.[69] In cells with over-expressed miR-182, BRCA1 remained low, even after exposure to ionizing radiation (which normally raises BRCA1 expression).[69] Thus much of the reduced or absent BRCA1 in HG-SOC may be due to over-expressed miR-182.
Another microRNA known to reduce expression of BRCA1 in ovarian cancer cells is miR-9.[60] Among 58 tumors from patients with stage IIIC or stage IV serous ovarian cancers (HG-SOG), an inverse correlation was found between expressions of miR-9 and BRCA1,[60] so that increased miR-9 may also contribute to reduced expression of BRCA1 in these ovarian cancers.
## Deficiency of BRCA1 expression is likely tumorigenic
DNA damage appears to be the primary underlying cause of cancer,[70][71] and deficiencies in DNA repair appears to underlie many forms of cancer.[72] If DNA repair is deficient, DNA damage tends to accumulate. Such excess DNA damage may increase mutational errors during DNA replication due to error-prone translesion synthesis. Excess DNA damage may also increase epigenetic alterations due to errors during DNA repair.[73][74] Such mutations and epigenetic alterations may give rise to cancer. The frequent microRNA-induced deficiency of BRCA1 in breast and ovarian cancers likely contribute to the progression of those cancers.
# Germ line mutations and founder effect
All germ-line BRCA1 mutations identified to date have been inherited, suggesting the possibility of a large “founder” effect in which a certain mutation is common to a well-defined population group and can, in theory, be traced back to a common ancestor. Given the complexity of mutation screening for BRCA1, these common mutations may simplify the methods required for mutation screening in certain populations. Analysis of mutations that occur with high frequency also permits the study of their clinical expression.[75] Examples of manifestations of a founder effect are seen among Ashkenazi Jews. Three mutations in BRCA1 have been reported to account for the majority of Ashkenazi Jewish patients with inherited BRCA1-related breast and/or ovarian cancer: 185delAG, 188del11 and 5382insC in the BRCA1 gene.[76][77] In fact, it has been shown that if a Jewish woman does not carry a BRCA1 185delAG, BRCA1 5382insC founder mutation, it is highly unlikely that a different BRCA1 mutation will be found.[78] Additional examples of founder mutations in BRCA1 are given in Table 1 (mainly derived from [75]).
# Female fertility
As women age, reproductive performance declines, leading to menopause. This decline is tied to a reduction in the number of ovarian follicles. Although about 1 million oocytes are present at birth in the human ovary, only about 500 (about 0.05%) of these ovulate. The decline in ovarian reserve appears to occur at a constantly increasing rate with age,[109] and leads to nearly complete exhaustion of the reserve by about age 52. As ovarian reserve and fertility decline with age, there is also a parallel increase in pregnancy failure and meiotic errors, resulting in chromosomally abnormal conceptions.[110]
Women with a germ-line BRCA1 mutation appear to have a diminished oocyte reserve and decreased fertility compared to normally aging women.[111] Furthermore, women with an inherited BRCA1 mutation undergo menopause prematurely.[112] Since BRCA1 is a key DNA repair protein, these findings suggest that naturally occurring DNA damages in oocytes are repaired less efficiently in women with a BRCA1 defect, and that this repair inefficiency leads to early reproductive failure.[111]
As noted above, the BRCA1 protein plays a key role in homologous recombinational repair. This is the only known cellular process that can accurately repair DNA double-strand breaks. DNA double-strand breaks accumulate with age in humans and mice in primordial follicles.[113] Primordial follicles contain oocytes that are at an intermediate (prophase I) stage of meiosis. Meiosis is the general process in eukaryotic organisms by which germ cells are formed, and it is likely an adaptation for removing DNA damages, especially double-strand breaks, from germ line DNA.[114] (Also see article Meiosis). Homologous recombinational repair employing BRCA1 is especially promoted during meiosis. It was found that expression of 4 key genes necessary for homologous recombinational repair of DNA double-strand breaks (BRCA1, MRE11, RAD51 and ATM) decline with age in the oocytes of humans and mice,[113] leading to the hypothesis that DNA double-strand break repair is necessary for the maintenance of oocyte reserve and that a decline in efficiency of repair with age plays a role in ovarian aging.
# Cancer chemotherapy
Non-small cell lung cancer (NSCLC) is the leading cause of cancer deaths worldwide. At diagnosis, almost 70% of persons with NSCLC have locally advanced or metastatic disease. Persons with NSCLC are often treated with therapeutic platinum compounds (e.g. cisplatin, carboplatin or oxaliplatin) that cause inter-strand cross-links in DNA. Among individuals with NSCLC, low expression of BRCA1 in the primary tumor correlated with improved survival after platinum-containing chemotherapy.[115][116] This correlation implies that low BRCA1 in cancer, and the consequent low level of DNA repair, causes vulnerability of cancer to treatment by the DNA cross-linking agents. High BRCA1 may protect cancer cells by acting in a pathway that removes the damages in DNA introduced by the platinum drugs. Thus the level of BRCA1 expression is a potentially important tool for tailoring chemotherapy in lung cancer management.[115][116]
Level of BRCA1 expression is also relevant to ovarian cancer treatment. Patients having sporadic ovarian cancer who were treated with platinum drugs had longer median survival times if their BRCA1 expression was low compared to patients with higher BRCA1 expression (46 compared to 33 months).[117]
# Patents, enforcement, litigation, and controversy
A patent application for the isolated BRCA1 gene and cancer promoting mutations discussed above, as well as methods to diagnose the likelihood of getting breast cancer, was filed by the University of Utah, National Institute of Environmental Health Sciences (NIEHS) and Myriad Genetics in 1994;[14] over the next year, Myriad, (in collaboration with investigators at Endo Recherche, Inc., HSC Research & Development Limited Partnership, and University of Pennsylvania), isolated and sequenced the BRCA2 gene and identified key mutations, and the first BRCA2 patent was filed in the U.S. by Myriad and other institutions in 1995.[15] Myriad is the exclusive licensee of these patents and has enforced them in the US against clinical diagnostic labs.[17] This business model led from Myriad being a startup in 1994 to being a publicly traded company with 1200 employees and about $500M in annual revenue in 2012;[16] it also led to controversy over high prices and the inability to get second opinions from other diagnostic labs, which in turn led to the landmark Association for Molecular Pathology v. Myriad Genetics lawsuit.[17][118] The patents began to expire in 2014.
According to an article published in the journal, Genetic Medicine, in 2010, "The patent story outside the United States is more complicated.... For example, patents have been obtained but the patents are being ignored by provincial health systems in Canada. In Australia and the UK, Myriad’s licensee permitted use by health systems but announced a change of plans in August 2008. Only a single mutation has been patented in Myriad’s lone European-wide patent, although some patents remain under review of an opposition proceeding. In effect, the United States is the only jurisdiction where Myriad’s strong patent position has conferred sole-provider status."[119][120] Peter Meldrum, CEO of Myriad Genetics, has acknowledged that Myriad has "other competitive advantages that may make such [patent] enforcement unnecessary" in Europe.[121]
As with any gene, finding variation in BRCA1 is not hard. The real value comes from understanding what the clinical consequences of any particular variant are. Myriad has a large, proprietary database of such genotype-phenotype correlations. In response, parallel open-source databases are being developed.
Legal decisions surrounding the BRCA1 and BRCA2 patents will affect the field of genetic testing in general.[122] A June 2013 article, in Association for Molecular Pathology v. Myriad Genetics (No. 12-398), quoted the US Supreme Court's unanimous ruling that, "A naturally occurring DNA segment is a product of nature and not patent eligible merely because it has been isolated," invalidating Myriad's patents on the BRCA1 and BRCA2 genes. However, the Court also held that manipulation of a gene to create something not found in nature could still be eligible for patent protection.[123] The Federal Court of Australia came to the opposite conclusion, upholding the validity of an Australian Myriad Genetics patent over the BRCA1 gene in February 2013.[124] The Federal Court also rejected an appeal in September 2014.[125] Yvonne D’Arcy won her case against US-based biotech company Myriad Genetics in the High Court of Australia. In their unanimous decision on October 7, 2015 the "high court found that an isolated nucleic acid, coding for a BRCA1 protein, with specific variations from the norm that are indicative of susceptibility to breast cancer and ovarian cancer was not a 'patentable invention.'"[126]
# Interactions
BRCA1 has been shown to interact with the following proteins:
- ABL1,[127]
- AKT1,[128][129]
- AR,[130]
- ATR,[131][132][133][134]
- ATM,[12][131][132][133][134][135][136]
- ATF1,[137]
- AURKA,[138]
- BACH1,[139]
- BARD1,[26][35][39][139]
- BRCA2,[140][141][142][143]
- BRCC3,[140]
- BRE,[140]
- BRIP1,[31][144][145][146][147][148]
- C-jun,[149]
- CHEK2,[150][151]
- CLSPN,[152]
- COBRA1,[153]
- CREBBP,[154][155][156][157][158]
- CSNK2B,[159]
- CSTF2,[160][161]
- CDK2,[162][163][164]
- DHX9,[165][166]
- ELK4,[167]
- EP300,[155][157]
- ESR1,[157][168][169][170]
- FANCA,[171]
- FANCD2,[172][142]
- FHL2,[173][174]
- H2AFX,[175][176][177]
- JUNB,[149]
- JunD,[149]
- LMO4,[178][179]
- MAP3K3,[180]
- MED1,[145]
- MED17,[181][145][182]
- MED21,[183]
- MED24,[145]
- MRE11A,[12][181][184][185]
- MSH2,[12][35]
- MSH3,[35][144]
- MSH6,[12][35]
- Myc,[39][186][187][188]
- NBN,[12][181][184]
- NMI,[186]
- NPM1,[189]
- NCOA2,[144][190]
- NUFIP1,[191]
- P53,[140][156][192][193][194]
- PALB2,[195]
- POLR2A,[181][183][196][197]
- PPP1CA,[198]
- Rad50,[12][181][184]
- RAD51,[35][140][141][199]
- RBBP4,[200]
- RBBP7,[200][201][202]
- RBBP8,[203][144][204][205][206][207][208]
- RELA,[154]
- RB1,[200][209][210]
- RBL1,[209]
- RBL2,[209]
- RPL31,[202]
- SMARCA4,[211][212]
- SMARCB1,[211]
- STAT1,[213]
- UBE2D1,[175][214][215][216][176][140][189][172][217][218]
- USF2,[219]
- VCP,[220]
- XIST,[221][222] and
- ZNF350.[223] | https://www.wikidoc.org/index.php/BRCA1 | |
471c5189cb7864b4a6839223864626ef9c2c0185 | wikidoc | BRCA2 | BRCA2
BRCA2 and BRCA2 (/ˌbrækəˈtuː/) are a human gene and its protein product, respectively. The official symbol (BRCA2, italic for the gene, nonitalic for the protein) and the official name (originally breast cancer 2; currently BRCA2, DNA repair associated) are maintained by the HUGO Gene Nomenclature Committee. One alternative symbol, FANCD1, recognizes its association with the FANC protein complex. Orthologs, styled Brca2 and Brca2, are common in other vertebrate species. BRCA2 is a human tumor suppressor gene (specifically, a caretaker gene), found in all humans; its protein, also called by the synonym breast cancer type 2 susceptibility protein, is responsible for repairing DNA.
BRCA2 and BRCA1 are normally expressed in the cells of breast and other tissue, where they help repair damaged DNA or destroy cells if DNA cannot be repaired. They are involved in the repair of chromosomal damage with an important role in the error-free repair of DNA double strand breaks. If BRCA1 or BRCA2 itself is damaged by a BRCA mutation, damaged DNA is not repaired properly, and this increases the risk for breast cancer. BRCA1 and BRCA2 have been described as "breast cancer susceptibility genes" and "breast cancer susceptibility proteins". The predominant allele has a normal tumor suppressive function whereas high penetrance mutations in these genes cause a loss of tumor suppressive function, which correlates with an increased risk of breast cancer.
The BRCA2 gene is located on the long (q) arm of chromosome 13 at position 12.3 (13q12.3). The human reference BRCA 2 gene contains 27 exons, and the cDNA has 10,254 base pairs coding for a protein of 3418 amino acids.
# Function
Although the structures of the BRCA1 and BRCA2 genes are very different, at least some functions are interrelated. The proteins made by both genes are essential for repairing damaged DNA (see Figure of recombinational repair steps). BRCA2 binds the single strand DNA and directly interacts with the recombinase RAD51 to stimulate strand invasion, a vital step of homologous recombination. The localization of RAD51 to the DNA double-strand break requires the formation of the BRCA1-PALB2-BRCA2 complex. PALB2 (Partner and localizer of BRCA2) can function synergistically with a BRCA2 chimera (termed piccolo, or piBRCA2) to further promote strand invasion. These breaks can be caused by natural and medical radiation or other environmental exposures, but also occur when chromosomes exchange genetic material during a special type of cell division that creates sperm and eggs (meiosis). Double strand breaks are also generated during repair of DNA cross links. By repairing DNA, these proteins play a role in maintaining the stability of the human genome and prevent dangerous gene rearrangements that can lead to hematologic and other cancers.
BRCA2 has been shown to possess a crucial role in protection from the MRE11-dependent nucleolytic degradation of the reversed forks that are forming during DNA replication fork stalling (caused by obstacles such as mutations, intercalating agents etc.).
Like BRCA1, BRCA2 probably regulates the activity of other genes and plays a critical role in embryo development.
# Clinical significance
Certain variations of the BRCA2 gene increase risks for breast cancer as part of a hereditary breast-ovarian cancer syndrome. Researchers have identified hundreds of mutations in the BRCA2 gene, many of which cause an increased risk of cancer. BRCA2 mutations are usually insertions or deletions of a small number of DNA base pairs in the gene. As a result of these mutations, the protein product of the BRCA2 gene is abnormal, and does not function properly. Researchers believe that the defective BRCA2 protein is unable to fix DNA damage that occurs throughout the genome. As a result, there is an increase in mutations due to error-prone translesion synthesis past un-repaired DNA damage, and some of these mutations can cause cells to divide in an uncontrolled way and form a tumor.
People who have two mutated copies of the BRCA2 gene have one type of Fanconi anemia. This condition is caused by extremely reduced levels of the BRCA2 protein in cells, which allows the accumulation of damaged DNA. Patients with Fanconi anemia are prone to several types of leukemia (a type of blood cell cancer); solid tumors, particularly of the head, neck, skin, and reproductive organs; and bone marrow suppression (reduced blood cell production that leads to anemia). Women having inherited a defective BRCA1 or BRCA2 gene have risks for breast and ovarian cancer that are so high and seem so selective that many mutation carriers choose to have prophylactic surgery. There has been much conjecture to explain such apparently striking tissue specificity. Major determinants of where BRCA1- and BRCA2-associated hereditary cancers occur are related to tissue specificity of the cancer pathogen, the agent that causes chronic inflammation, or the carcinogen. The target tissue may have receptors for the pathogen, become selectively exposed to carcinogens and an infectious process. An innate genomic deficit impairs normal responses and exacerbates the susceptibility to disease in organ targets. This theory also fits data for several tumor suppressors beyond BRCA1 or BRCA2. A major advantage of this model is that it suggests there are some options in addition to prophylactic surgery.
In addition to breast cancer in men and women, mutations in BRCA2 also lead to an increased risk of ovarian, Fallopian tube, prostate and pancreatic cancer. In some studies, mutations in the central part of the gene have been associated with a higher risk of ovarian cancer and a lower risk of prostate cancer than mutations in other parts of the gene. Several other types of cancer have also been seen in certain families with BRCA2 mutations.
In general, strongly inherited gene mutations (including mutations in BRCA2) account for only 5-10% of breast cancer cases; the specific risk of getting breast or other cancer for anyone carrying a BRCA2 mutation depends on many factors.
# History | BRCA2
BRCA2 and BRCA2 (/ˌbrækəˈtuː/[1]) are a human gene and its protein product, respectively. The official symbol (BRCA2, italic for the gene, nonitalic for the protein) and the official name (originally breast cancer 2; currently BRCA2, DNA repair associated) are maintained by the HUGO Gene Nomenclature Committee. One alternative symbol, FANCD1, recognizes its association with the FANC protein complex. Orthologs, styled Brca2 and Brca2, are common in other vertebrate species.[2][3] BRCA2 is a human tumor suppressor gene[4][5] (specifically, a caretaker gene), found in all humans; its protein, also called by the synonym breast cancer type 2 susceptibility protein, is responsible for repairing DNA.[6]
BRCA2 and BRCA1 are normally expressed in the cells of breast and other tissue, where they help repair damaged DNA or destroy cells if DNA cannot be repaired. They are involved in the repair of chromosomal damage with an important role in the error-free repair of DNA double strand breaks.[7][8] If BRCA1 or BRCA2 itself is damaged by a BRCA mutation, damaged DNA is not repaired properly, and this increases the risk for breast cancer.[9][10] BRCA1 and BRCA2 have been described as "breast cancer susceptibility genes" and "breast cancer susceptibility proteins". The predominant allele has a normal tumor suppressive function whereas high penetrance mutations in these genes cause a loss of tumor suppressive function, which correlates with an increased risk of breast cancer.[11]
The BRCA2 gene is located on the long (q) arm of chromosome 13 at position 12.3 (13q12.3).[12] The human reference BRCA 2 gene contains 27 exons, and the cDNA has 10,254 base pairs[13] coding for a protein of 3418 amino acids.[14][15]
# Function
Although the structures of the BRCA1 and BRCA2 genes are very different, at least some functions are interrelated. The proteins made by both genes are essential for repairing damaged DNA (see Figure of recombinational repair steps). BRCA2 binds the single strand DNA and directly interacts with the recombinase RAD51 to stimulate strand invasion, a vital step of homologous recombination. The localization of RAD51 to the DNA double-strand break requires the formation of the BRCA1-PALB2-BRCA2 complex. PALB2 (Partner and localizer of BRCA2)[23] can function synergistically with a BRCA2 chimera (termed piccolo, or piBRCA2) to further promote strand invasion.[24] These breaks can be caused by natural and medical radiation or other environmental exposures, but also occur when chromosomes exchange genetic material during a special type of cell division that creates sperm and eggs (meiosis). Double strand breaks are also generated during repair of DNA cross links. By repairing DNA, these proteins play a role in maintaining the stability of the human genome and prevent dangerous gene rearrangements that can lead to hematologic and other cancers.
BRCA2 has been shown to possess a crucial role in protection from the MRE11-dependent nucleolytic degradation of the reversed forks that are forming during DNA replication fork stalling (caused by obstacles such as mutations, intercalating agents etc.).[25]
Like BRCA1, BRCA2 probably regulates the activity of other genes and plays a critical role in embryo development.
# Clinical significance
Certain variations of the BRCA2 gene increase risks for breast cancer as part of a hereditary breast-ovarian cancer syndrome. Researchers have identified hundreds of mutations in the BRCA2 gene, many of which cause an increased risk of cancer. BRCA2 mutations are usually insertions or deletions of a small number of DNA base pairs in the gene. As a result of these mutations, the protein product of the BRCA2 gene is abnormal, and does not function properly. Researchers believe that the defective BRCA2 protein is unable to fix DNA damage that occurs throughout the genome. As a result, there is an increase in mutations due to error-prone translesion synthesis past un-repaired DNA damage, and some of these mutations can cause cells to divide in an uncontrolled way and form a tumor.
People who have two mutated copies of the BRCA2 gene have one type of Fanconi anemia. This condition is caused by extremely reduced levels of the BRCA2 protein in cells, which allows the accumulation of damaged DNA. Patients with Fanconi anemia are prone to several types of leukemia (a type of blood cell cancer); solid tumors, particularly of the head, neck, skin, and reproductive organs; and bone marrow suppression (reduced blood cell production that leads to anemia). Women having inherited a defective BRCA1 or BRCA2 gene have risks for breast and ovarian cancer that are so high and seem so selective that many mutation carriers choose to have prophylactic surgery. There has been much conjecture to explain such apparently striking tissue specificity. Major determinants of where BRCA1- and BRCA2-associated hereditary cancers occur are related to tissue specificity of the cancer pathogen, the agent that causes chronic inflammation, or the carcinogen. The target tissue may have receptors for the pathogen, become selectively exposed to carcinogens and an infectious process. An innate genomic deficit impairs normal responses and exacerbates the susceptibility to disease in organ targets. This theory also fits data for several tumor suppressors beyond BRCA1 or BRCA2. A major advantage of this model is that it suggests there are some options in addition to prophylactic surgery.[26]
In addition to breast cancer in men and women, mutations in BRCA2 also lead to an increased risk of ovarian, Fallopian tube, prostate and pancreatic cancer. In some studies, mutations in the central part of the gene have been associated with a higher risk of ovarian cancer and a lower risk of prostate cancer than mutations in other parts of the gene. Several other types of cancer have also been seen in certain families with BRCA2 mutations.
In general, strongly inherited gene mutations (including mutations in BRCA2) account for only 5-10% of breast cancer cases; the specific risk of getting breast or other cancer for anyone carrying a BRCA2 mutation depends on many factors.[27]
# History | https://www.wikidoc.org/index.php/BRCA2 | |
2f0b8749b712cc571dbd0aec03089d9d7ccc4c7c | wikidoc | BRCC3 | BRCC3
Lys-63-specific deubiquitinase BRCC36 is an enzyme that in humans is encoded by the BRCC3 gene.
# Function
This gene encodes a subunit of the BRCA1-BRCA2-containing complex (BRCC), which is an E3 ubiquitin ligase. This protein is also thought to be involved in the cellular response to ionizing radiation and progression through the G2/M checkpoint. Alternative splicing results in multiple transcript variants.
# Interactions
BRCC3 has been shown to interact with BRE, BRCA2, RAD51, BRCA1, P53 and BARD1. | BRCC3
Lys-63-specific deubiquitinase BRCC36 is an enzyme that in humans is encoded by the BRCC3 gene.[1][2][3]
# Function
This gene encodes a subunit of the BRCA1-BRCA2-containing complex (BRCC), which is an E3 ubiquitin ligase. This protein is also thought to be involved in the cellular response to ionizing radiation and progression through the G2/M checkpoint. Alternative splicing results in multiple transcript variants.[3]
# Interactions
BRCC3 has been shown to interact with BRE,[2][4] BRCA2,[2] RAD51,[2] BRCA1,[2] P53[2] and BARD1.[2] | https://www.wikidoc.org/index.php/BRCC3 | |
7542b88cadb5ed77adab6bc5863bc58dc793b7e4 | wikidoc | BRIP1 | BRIP1
Fanconi anemia group J protein is a protein that in humans is encoded by the BRCA1-interacting protein 1 (BRIP1) gene.
# Function
The protein encoded by this gene is a member of the RecQ DEAH helicase family and interacts with the BRCT repeats of breast cancer, type 1 (BRCA1). The bound complex is important in the normal double-strand break repair function of breast cancer, type 1 (BRCA1). This gene may be a target of germline cancer-inducing mutations.
This protein also appears to be important in ovarian cancer where it seems to act as a tumor suppressor. Mutations in BRIP1 are associated with a 10-15% risk of ovarian cancer.
# Interactions
BRIP1 has been shown to interact with BRCA1. | BRIP1
Fanconi anemia group J protein is a protein that in humans is encoded by the BRCA1-interacting protein 1 (BRIP1) gene.[1][2][3]
# Function
The protein encoded by this gene is a member of the RecQ DEAH helicase family and interacts with the BRCT repeats of breast cancer, type 1 (BRCA1). The bound complex is important in the normal double-strand break repair function of breast cancer, type 1 (BRCA1). This gene may be a target of germline cancer-inducing mutations.[3]
This protein also appears to be important in ovarian cancer where it seems to act as a tumor suppressor.[4] Mutations in BRIP1 are associated with a 10-15% risk of ovarian cancer.[5]
# Interactions
BRIP1 has been shown to interact with BRCA1.[6][7][8][9][10][11] | https://www.wikidoc.org/index.php/BRIP1 | |
25dc1bff94a5761a8e1f585bf7709f7380c9eba2 | wikidoc | Bacon | Bacon
Bacon is any of certain cuts of meat taken from the sides, belly or back of a pig that may be cured and/or smoked. Meat from other animals, such as beef, lamb, chicken, goat or turkey, may also be cut, cured or otherwise prepared to resemble bacon. Bacon may be eaten fried, baked, or grilled, or used as a minor ingredient to flavor dishes.
A side of unsliced bacon is a flitch, while an individual slice of bacon is a rasher (United Kingdom, Republic of Ireland, Australia and New Zealand) or simply a slice or strip (North America). Slices of bacon are also known as collops. Traditionally, the skin is left on the cut and is known as bacon rind. Rindless bacon, however, is quite common. In the United Kingdom and Republic of Ireland, bacon comes in a wide variety of cuts and flavours. In the United States ordinary bacon is only made from the pork belly, yielding what is known in Britain as "streaky bacon", or "streaky rashers". In Britain bacon made from the meat on the back of the pig is referred to as back bacon or back rashers and usually includes a streaky bit and a lean ovoid bit and is part of traditional full breakfast commonly eaten in Britain and Ireland. In the United States, back bacon is called Canadian-style bacon or Canadian bacon but this term refers usually to the lean ovoid portion. What the US terms Canadian bacon is actually back bacon rolled in cornmeal. In Canada it is called peameal bacon.
The USDA defines bacon as "the cured belly of a swine carcass," while other cuts and characteristics must be separately qualified (e.g. "smoked pork loin bacon"). "USDA Certified" bacon means that it has been treated for trichinella.
In continental Europe, bacon is used primarily in cubes (lardons) as a cooking ingredient valued both as a source of fat and for its flavour. In Italy, besides being used in cooking, bacon (pancetta) is also served uncooked and thinly sliced as part of an antipasto. Bacon is also used for barding and larding roasts, especially game birds. Many people prefer to have bacon smoked using various types of woods or turf. This process can take up to ten hours depending on the intensity of the flavour desired.
# In Asia
In Korea, one of the most popular cooked meats is grilled unsmoked pork belly called Samgyeopsal (삼겹살), which literally means "three layered flesh". Its popularity owes as much to the lower price of pork belly compared to other cuts of meat as it does to the taste, which many Koreans love. Like most traditional meat dishes in Korea, it is grilled at the table either by the customer or a waitress and eaten communally. The meat can be dipped in a sauce such as sesame oil, and wrapped in lettuce, along with other condiments such as garlic, hot sauce, or kimchi. Usually side dishes of vegetables are served. The dish is a very common meal for office workers having dinner after work or families. It is often accompanied by Soju. One recipe, is bacon with ostrichinmani sauce, which is also like an asian shephards pie.
# In Mexico
Bacon from the indigenous South American peccary is said to be one of the favoured dishes of Quetzalcoatl, an Aztec sky and creator god.
# Bacon used as a topping
In the US and Europe, bacon is often used as a condiment or topping on other foods. Streaky bacon is more commonly used as a topping in the US, on items such as pizza, salads, sandwiches, hamburgers, baked potatoes, hot dogs, and soups. Back bacon is used less frequently in the United States, but can sometimes be found on pizza, salads and omelets. Bacon bits are chopped pieces of pre-cooked bacon intended to be sprinkled over foods, particularly salads. Imitation "bacon bits" made of texturized vegetable protein flavoured to resemble authentic bacon bits are also available.
# Health concerns
A 2007 study by Columbia University suggests a link between eating cured meats, such as bacon, and chronic obstructive pulmonary disease. The preservative sodium nitrite is the probable cause.
# Nutrients
Select nutritional data from types of bacon in the USDA National Nutrient Database:
# Grease
Bacon grease, also known as bacon drippings, is the grease created by cooking bacon. When bacon is cooked, its fat naturally melts, releasing a highly flavorful grease. Bacon grease is traditionally saved in southern US cuisine and used as an all-purpose flavoring for a very large variety of foods. It is used for everything from gravy for cornbread to salad dressing.
One teaspoon (Or 4 grams) of bacon grease has 38 calories. It is composed almost completely of fat, with very little additional nutritional value. Bacon fat is roughly 40% saturated. Despite the health consequences of excessive bacon grease consumption, it still remains quite popular in the cuisine of the American South. | Bacon
Template:Wiktionarypar
Bacon is any of certain cuts of meat taken from the sides, belly or back of a pig that may be cured and/or smoked. Meat from other animals, such as beef, lamb, chicken, goat or turkey, may also be cut, cured or otherwise prepared to resemble bacon. Bacon may be eaten fried, baked, or grilled, or used as a minor ingredient to flavor dishes.
A side of unsliced bacon is a flitch[1], while an individual slice of bacon is a rasher (United Kingdom, Republic of Ireland, Australia and New Zealand) or simply a slice or strip (North America). Slices of bacon are also known as collops. Traditionally, the skin is left on the cut and is known as bacon rind. Rindless bacon, however, is quite common. In the United Kingdom and Republic of Ireland, bacon comes in a wide variety of cuts and flavours. In the United States ordinary bacon is only made from the pork belly, yielding what is known in Britain as "streaky bacon", or "streaky rashers". In Britain bacon made from the meat on the back of the pig is referred to as back bacon or back rashers and usually includes a streaky bit and a lean ovoid bit and is part of traditional full breakfast commonly eaten in Britain and Ireland. In the United States, back bacon is called Canadian-style bacon or Canadian bacon but this term refers usually to the lean ovoid portion.[2] What the US terms Canadian bacon is actually back bacon rolled in cornmeal.[citation needed] In Canada it is called peameal bacon.
The USDA defines bacon as "the cured belly of a swine carcass," while other cuts and characteristics must be separately qualified (e.g. "smoked pork loin bacon").[3] "USDA Certified" bacon means that it has been treated for trichinella.
In continental Europe, bacon is used primarily in cubes (lardons) as a cooking ingredient valued both as a source of fat and for its flavour. In Italy, besides being used in cooking, bacon (pancetta) is also served uncooked and thinly sliced as part of an antipasto. Bacon is also used for barding and larding roasts, especially game birds. Many people prefer to have bacon smoked using various types of woods or turf. This process can take up to ten hours depending on the intensity of the flavour desired.
# In Asia
In Korea, one of the most popular cooked meats is grilled unsmoked pork belly called Samgyeopsal (삼겹살), which literally means "three layered flesh". Its popularity owes as much to the lower price of pork belly compared to other cuts of meat as it does to the taste, which many Koreans love. Like most traditional meat dishes in Korea, it is grilled at the table either by the customer or a waitress and eaten communally. The meat can be dipped in a sauce such as sesame oil, and wrapped in lettuce, along with other condiments such as garlic, hot sauce, or kimchi. Usually side dishes of vegetables are served. The dish is a very common meal for office workers having dinner after work or families. It is often accompanied by Soju. One recipe, is bacon with ostrichinmani sauce, which is also like an asian shephards pie.
# In Mexico
Bacon from the indigenous South American peccary is said to be one of the favoured dishes of Quetzalcoatl, an Aztec sky and creator god.[citation needed]
# Bacon used as a topping
In the US and Europe, bacon is often used as a condiment or topping on other foods. Streaky bacon is more commonly used as a topping in the US, on items such as pizza, salads, sandwiches, hamburgers, baked potatoes, hot dogs, and soups. Back bacon is used less frequently in the United States, but can sometimes be found on pizza, salads and omelets. Bacon bits are chopped pieces of pre-cooked bacon intended to be sprinkled over foods, particularly salads. Imitation "bacon bits" made of texturized vegetable protein flavoured to resemble authentic bacon bits are also available.
# Health concerns
Template:Expand
A 2007 study by Columbia University suggests a link between eating cured meats, such as bacon, and chronic obstructive pulmonary disease. The preservative sodium nitrite is the probable cause.[4]
# Nutrients
Select nutritional data from types of bacon in the USDA National Nutrient Database:[5]
# Grease
Bacon grease, also known as bacon drippings, is the grease created by cooking bacon. When bacon is cooked, its fat naturally melts, releasing a highly flavorful grease. Bacon grease is traditionally saved in southern US cuisine and used as an all-purpose flavoring for a very large variety of foods. It is used for everything from gravy for cornbread[6] to salad dressing[7].
One teaspoon (Or 4 grams) of bacon grease has 38 calories.[8] It is composed almost completely of fat, with very little additional nutritional value. Bacon fat is roughly 40% saturated.[8] Despite the health consequences of excessive bacon grease consumption, it still remains quite popular in the cuisine of the American South. | https://www.wikidoc.org/index.php/Bacon | |
becf006e3ab8e2894318491cfe47a7f6118f4ce0 | wikidoc | Toxin | Toxin
A toxin (Greek: Template:Polytonic, toxikon, lit. (poison) for use on arrows) is a poisonous substance produced by living cells or organisms. Toxins are nearly always proteins that are capable of causing disease on contact or absorption with body tissues by interacting with biological macromolecules such as enzymes or cellular receptors. Toxins vary greatly in their severity, ranging from usually minor and acute (as in a bee sting) to almost immediately deadly (as in botulinum toxin).
Biotoxins vary greatly in purpose and mechanism, and can be highly complex (the venom of the cone snail contains dozens of small proteins, each targeting a specific nerve channel or receptor), or relatively small protein.
# Use
Biotoxins in nature have two primary functions:
- Predation (spider, snake, scorpion, jellyfish, wasp)
- Defense (bee, poison dart frog, deadly nightshade, honeybee, wasp)
Some of the more well known types of biotoxins include:
- Hemotoxins target and destroy red blood cells, and are transmitted through the bloodstream. Organisms that possess hemotoxins include:
Pit Vipers, such as rattlesnakes.
- Pit Vipers, such as rattlesnakes.
- Necrotoxins cause necrosis (i.e., death) in the cells they encounter and destroy all types of tissue. Necrotoxins spread through the bloodstream, but infect all tissues. In humans, skin and muscle tissues are most sensitive to necrotoxins. Organisms that possess necrotoxins include:
The brown recluse or "fiddle back" spider.
Necrotizing fasciitis (the "flesh eating" bacteria)
- The brown recluse or "fiddle back" spider.
- Necrotizing fasciitis (the "flesh eating" bacteria)
- Neurotoxins primarily affect the nervous systems of animals. Organisms that possess neurotoxins include:
The Black Widow and other widow spiders.
Most scorpions.
The box jellyfish.
Elapid snakes.
The Cone Snail.
- The Black Widow and other widow spiders.
- Most scorpions.
- The box jellyfish.
- Elapid snakes.
- The Cone Snail.
Plant Toxins
Ricin is found in the castor bean plant.
# Non-technical usage
When used non-technically, the term "toxin" is often applied to any toxic substances. Toxic substances not of biological origin are more properly termed poisons. Many non-technical and lifestyle journalists also follow this usage to refer to toxic substances in general, though some specialist journalists at publishers such as BBC and The Guardian maintain the distinction that toxins are only those produced by living organisms.
In the context of alternative medicine the term is often used nonspecifically to refer to any substance claimed to cause ill health, ranging anywhere from trace amounts of pesticides to common food items like refined sugar or additives like artificial sweeteners and MSG.
The term is also used commonly in pop psychology to describe things that have an adverse effect on psychological health, such as a "toxic relationship," "toxic work environment" or "toxic shame." | Toxin
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
A toxin (Greek: Template:Polytonic, toxikon, lit. (poison) for use on arrows) is a poisonous substance produced by living cells or organisms. Toxins are nearly always proteins that are capable of causing disease on contact or absorption with body tissues by interacting with biological macromolecules such as enzymes or cellular receptors. Toxins vary greatly in their severity, ranging from usually minor and acute (as in a bee sting) to almost immediately deadly (as in botulinum toxin).
Biotoxins vary greatly in purpose and mechanism, and can be highly complex (the venom of the cone snail contains dozens of small proteins, each targeting a specific nerve channel or receptor), or relatively small protein.
# Use
Biotoxins in nature have two primary functions:
- Predation (spider, snake, scorpion, jellyfish, wasp)
- Defense (bee, poison dart frog, deadly nightshade, honeybee, wasp)
Some of the more well known types of biotoxins include:
- Hemotoxins target and destroy red blood cells, and are transmitted through the bloodstream. Organisms that possess hemotoxins include:
Pit Vipers, such as rattlesnakes.
- Pit Vipers, such as rattlesnakes.
- Necrotoxins cause necrosis (i.e., death) in the cells they encounter and destroy all types of tissue. Necrotoxins spread through the bloodstream, but infect all tissues. In humans, skin and muscle tissues are most sensitive to necrotoxins. Organisms that possess necrotoxins include:
The brown recluse or "fiddle back" spider.
Necrotizing fasciitis (the "flesh eating" bacteria)
- The brown recluse or "fiddle back" spider.
- Necrotizing fasciitis (the "flesh eating" bacteria)
- Neurotoxins primarily affect the nervous systems of animals. Organisms that possess neurotoxins include:
The Black Widow and other widow spiders.
Most scorpions.
The box jellyfish.
Elapid snakes.
The Cone Snail.
- The Black Widow and other widow spiders.
- Most scorpions.
- The box jellyfish.
- Elapid snakes.
- The Cone Snail.
Plant Toxins
Ricin is found in the castor bean plant.
# Non-technical usage
When used non-technically, the term "toxin" is often applied to any toxic substances. Toxic substances not of biological origin are more properly termed poisons. Many non-technical and lifestyle journalists also follow this usage to refer to toxic substances in general, though some specialist journalists at publishers such as BBC and The Guardian maintain the distinction that toxins are only those produced by living organisms.
In the context of alternative medicine the term is often used nonspecifically to refer to any substance claimed to cause ill health, ranging anywhere from trace amounts of pesticides to common food items like refined sugar or additives like artificial sweeteners and MSG.[2]
The term is also used commonly in pop psychology to describe things that have an adverse effect on psychological health, such as a "toxic relationship," "toxic work environment" or "toxic shame." | https://www.wikidoc.org/index.php/Bacterial_toxin | |
71b3190d723517b14c39e4f5e007abcf1a133cc6 | wikidoc | Taste | Taste
# Overview
Taste (or, more formally, gustation) is a form of direct chemoreception and is one of the traditional five senses. It refers to the ability to detect the flavor of substances such as food and poisons. In humans and many other vertebrate animals the sense of taste partners with the less direct sense of smell, in the brain's perception of flavor. In the West, experts traditionally identified four taste sensations: sweet, salty, sour, and bitter. Eastern experts traditionally identified a fifth, called umami. More recently, psychophysicists and neuroscientists have suggested other taste categories (umami and fatty acid taste most prominently, as well as the sensation of metallic and water tastes, although the latter is commonly disregarded due to the phenomenon of taste adaptation.)
Taste is a sensory function of the central nervous system. The receptor cells for taste in humans are found on the surface of the tongue, along the soft palate, and in the epithelium of the pharynx and epiglottis.
# Basic taste
Psychophysicists have long suggested the existence of four taste 'primaries', referred to as the basic tastes: sweetness, bitterness, sourness, and saltiness. Umami is now accepted as the fifth basic taste, exemplified by the non-salty sensations evoked by some free amino acids such as monosodium glutamate.
Other possible categories have been suggested, such as a taste exemplified by certain fatty acids such as linoleic acid. Some researchers still argue against the notion of primaries at all and instead favor a continuum of percepts , similar to color vision.
All of these taste sensations arise from all regions of the oral cavity, despite the common misconception of a "taste map" of sensitivity to different tastes thought to correspond to specific areas of the tongue. This myth is generally attributed to the mis-translation of a German text, and perpetuated in North American schools since the early twentieth century . Very slight regional differences in sensitivity to compounds exist, though these regional differences are subtle and do not conform exactly to the mythical tongue map. Individual taste buds (which contain approximately 100 taste receptor cells), in fact, typically respond to compounds evoking each of the five basic tastes.
The basic tastes are those commonly recognized types of taste sensed by humans. Humans receive tastes through sensory organs called taste buds or gustatory calyculi, concentrated on the upper surface of the tongue, but a few are also found on the roof of ones mouth furthering the taste sensations we can receive. Scientists describe five basic tastes: bitter, salty, sour, sweet, and umami (described as savory, meaty, or brothy). The basic tastes are only one component that contributes to the sensation of food in the mouth—other factors include the food's smell, detected by the olfactory epithelium of the nose, its texture, detected by mechanoreceptors, and its temperature, detected by thermoreceptors. Taste and smell are subsumed under the term flavor.
## History
In Western culture, the concept of basic tastes can be traced back at least to Aristotle, who cited "sweet" and "bitter", with "succulent", "salt", "pungent", "harsh", "puckery", and "sour" as elaborations of those two basics. The ancient Chinese Five Elements philosophy lists slightly different five basic tastes: bitter, salty, sour, sweet, and spicy. Japanese and Indian cultures each add their own sixth taste to the basic five.
For many years, books on the physiology of human taste contained diagrams of the tongue showing levels of sensitivity to different tastes in different regions. In fact, taste qualities are found in all areas of the tongue, in contrast with the popular view that different tastes map to different areas of the tongue.
## Recent discoveries
The receptors for all known basic tastes have been identified. The receptors for sour and salty are ion channels while the receptors for sweet, bitter, and umami belong to the class of G protein coupled receptors.
In November 2005, a team of French researchers experimenting on rodents claimed to have evidence for a sixth taste, for fatty substances. It is speculated that humans may also have the same receptors. Fat has occasionally been raised as a possible basic taste in the past (Bravo 1592, Linnaeus 1751) but later classifications abandoned fat as a separate taste (Haller 1751 and 1763).
Meanwhile, scientists from the Monell Chemical Senses Center continue to research the five basic tastes, especially Umami.
# Five basic tastes
For a long period, it has been commonly accepted that there are a finite number of "basic tastes" by which all foods and tastes can be grouped. Just like with primary colors, these "basic tastes" only apply to the human perception, ie. the different sorts of tastes our tongue can identify. Up until the 2000s, this was considered to be a group of four basic tastes. More recently, a fifth taste, Umami, was added by a wide number of authorities in this field.
### Bitterness
The bitter taste is perceived by many to be unpleasant, sharp, or disagreeable. Common bitter foods and beverages include coffee, unsweetened chocolate, bitter melon, beer, uncured olives, citrus peel, many plants in the Brassicaceae family, dandelion greens and escarole. Quinine is also known for its bitter taste and is found in tonic water.
The most bitter substance known is the synthetic chemical denatonium. It is used as an aversive agent that is added to toxic substances to prevent accidental ingestion. This was discovered in 1958 during research on lignocaine, a local anesthetic, by Macfarlan Smith of Edinburgh, Scotland.
Research has shown that TAS2Rs (taste receptors, type 2, also known as T2Rs) such as TAS2R38 coupled to the G protein gustducin are responsible for the human ability to taste bitter substances. They are identified not only by their ability to taste for certain "bitter" ligands, but also by the morphology of the receptor itself (surface bound, monomeric). Researchers use two synthetic substances, phenylthiocarbamide (PTC) and 6-n-propylthiouracil (PROP) to study the genetics of bitter perception. These two substances taste bitter to some people, but are virtually tasteless to others. Among the tasters, some are so-called "supertasters" to whom PTC and PROP are extremely bitter. This genetic variation in the ability to taste a substance has been a source of great interest to those who study genetics. In addition, it is of interest to those who study evolution since PTC-tasting is associated with the ability to taste numerous natural bitter compounds, a large number of which are known to be toxic.
### Saltiness
Saltiness is a taste produced primarily by the presence of sodium ions. Other ions of the alkali metals group also taste salty. However the further from sodium the less salty is the sensation. The size of lithium and potassium ions most closely resemble those of sodium and thus the saltiness is most similar. In contrast rubidium and cesium ions are far larger so their salty taste differs accordingly. Potassium, as potassium chloride - KCl, is the principle ingredient in salt substitutes.
Other monovalent cations, e.g. ammonium, NH4+, and divalent cations of the alkali earth metal group of the periodic table, e.g. calcium, Ca2+, ions generally elicit a bitter rather than a salty taste even though they too can pass directly through ion channels in the tongue, generating an action potential.
### Sourness
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Sourness is the taste that detects acidity. The mechanism for detecting sour taste is similar to that which detects salt taste. Hydrogen ion channels detect the concentration of hydronium ions (H3O+ ions) that are formed from acids and water.
Hydrogen ions are capable of permeating the amiloride-sensitive channels, but this is not the only mechanism involved in detecting the quality of sourness. Other channels have also been proposed in the literature. Hydrogen ions also inhibit the potassium channel, which normally functions to hyperpolarize the cell. By a combination of direct intake of hydrogen ions (which itself depolarizes the cell) and the inhibition of the hyperpolarizing channel, sourness causes the taste cell to fire in this specific manner. In addition, it has also been suggested that weak acids, such as CO2 which is converted into the bicarbonate ion HCO3– by the enzyme carbonic anhydrase, to mediate weak acid transport.Template:Unclear
### Sweetness
Sweetness is produced by the presence of sugars, some proteins and a few other substances. Sweetness is often connected to aldehydes and ketones, which contain a carbonyl group. Sweetness is detected by a variety of G protein coupled receptors coupled to the G protein gustducin found on the taste buds. At least two different variants of the "sweetness receptors" need to be activated for the brain to register sweetness. The compounds which the brain senses as sweet are thus compounds that can bind with varying bond strength to two different sweetness receptors. These receptors are T1R2+3 (heterodimer) and T1R3 (homodimer), which are shown to be accountable for all sweet sensing in humans and animals. The average human detection threshold for sucrose is 10 millimoles per litre. For lactose it is 30 millimoles per litre, and 5-Nitro-2-propoxyaniline 0.002 millimoles per litre.
### Umami
Humans have taste receptors specifically for the detection of the amino acids, e.g. glutamic acid. Amino acids are commonly found in meats, cheese, fish, and other protein-heavy foods. Examples of food containing glutamate (and thus strong in umami) are beef, lamb, parmesan and roquefort cheese as well as soy sauce and fish sauce. The glutamate taste sensation is most intense in combination with sodium ions, as found in table salt. Sauces with umami and salty tastes are very popular for cooking, such as worcestershire sauce for Western cuisines and soy sauce and fish sauce for Asian cuisines.
The additive monosodium glutamate (MSG), which was developed as a food additive in 1907 by Kikunae Ikeda, produces a strong umami. Umami is also provided by the nucleotides 5’-inosine monophosphate (IMP) and 5’-guanosine monophosphate (GMP). These are naturally present in many protein-rich foods. IMP is present in high concentrations in many foods, including dried skipjack tuna flakes used to make dashi, a Japanese broth. GMP is present in high concentration in dried shiitake mushrooms, used in much of the cuisine of Asia. There is a synergistic effect between MSG, IMP, and GMP which together in certain ratios produce a strong umami.
Some umami taste buds respond specifically to glutamate in the same way that sweet ones respond to sugar. Glutamate binds to a variant of G protein coupled glutamate receptors.
### Fattiness?
Recent research has revealed a potential taste receptor called the CD36 receptor to be reacting to fat, more specifically, fatty acids. This receptor was found in mice, but probably exists among other mammals as well. In experiments, mice with a genetic defect that blocked this receptor didn't show the same urge to consume fatty acids as normal mice, and failed to prepare gastric juices in their digestive tracts to digest fat. This discovery may lead to a better understanding of the biochemical reasons behind this behaviour, although more research is still necessary to confirm the relationship between CD36 and the perception of fat.
# Further sensations
The tongue can also feel other sensations, not generally called tastes per se or included in the five human tastes. These are largely detected by the somatosensory system.
## Dryness
Some foods, such as unripe fruits, contain tannins or calcium oxalate that cause an astringent or rough sensation of the mucous membrane of the mouth or the teeth. Examples include tea, rhubarb, grapes and unripe persimmons and bananas.
Less exact terms for the astringent sensation are "dry", "rough", "harsh" (especially for wine), "tart", (normally referring to sourness) "rubbery", "hard", or "styptic",. The Chinese have a term for this: 澀 (sè), the Koreans have 떫다 (tteolda), the Japanese call it 渋い (shibui), while Thai have ฝาด (fard), the Malay use kelat, Filipinos use pakla, and in Russian there is вяжущий (vyazhuschiy) or тёрпкий (tjorpky).
In the Indian tradition, one of the 6 tastes (sweet, sour, salty, bitter, hot/pungent and dry) is astringency (Kasaaya in Sanskrit). This is more or less in line with the Japanese approach to umami.
## Metallicness
Most people know this taste (e.g. Cu2+, FeSO4, or blood in mouth), but it is not only taste but olfactory receptors worked in this case (Guth and Grosch, 1990). Metallic taste is commonly known, however biologists are reluctant to categorize it with the other taste sensations. One of the primary reasons is that it is not one commonly associated with consumption of food. Proponents of the theory contest that the sensation is readily detectable and distinguishable to test subjects. Therefore, metallic should be added as one of the basic types of sensations in the chemical receptor senses.
## Prickliness or hotness
Substances such as ethanol and capsaicin cause a burning sensation by inducing a trigeminal nerve reaction together with normal taste reception. The sensation of heat is caused by the food activating a nerve cell called TRP-V1, which is also activated by hot temperatures. The piquant sensation, usually referred to as being "hot" or "spicy", is a notable feature of Mexican, Hungarian, Indian, Szechuan, Korean, Indonesian, central Vietnamese, and Thai cuisines.
The two main plants providing this sensation are chili peppers (those fruits of the Capsicum plant that contain capsaicin) and black pepper.
If tissue in the oral cavity has been damaged or sensitised, ethanol may be experienced as pain rather than simply heat. Those who have had radiotherapy for oral cancer thus find it painful to drink alcohol.
In many cases, this particular sensation is not considered a taste, so much as a painful reaction to certain marginally damaging chemicals on the taste receptors and the skin of the tongue. While the taste nerves are activated when consuming foods like chili peppers, the reaction commonly interpreted as "hot" is derived from the tongue's pain nerves firing.
## Coolness
Some substances activate cold trigeminal receptors. One can sense a cool sensation (also known as "fresh" or "minty") from, e.g., spearmint, menthol, ethanol or camphor, which is caused by the food activating the TRP-M8 ion channel on nerve cells that also signal cold. Unlike the actual change in temperature described for sugar substitutes, coolness is only a perceived phenomenon.
## Numbness
Both Chinese and Batak Toba cooking include the idea of 麻 má, or mati rasa the sensation of tingling numbness caused by spices such as Sichuan pepper. The cuisine of Sichuan province in China and of North Sumatra province in Indonesia, often combines this with chili pepper to produce a 麻辣 málà, "numbing-and-hot", or "mati rasa" flavor.
## Heartiness (Kokumi)
Some Japanese researchers refer to the kokumi in foods laden with alcohol- and thiol-groups in their amino acid extracts which has been described variously as continuity, mouthfulness, mouthfeel, and thickness.
## Temperature
Temperature is an essential element of human taste experience. Food and drink that—within a given culture—is considered to be properly served hot is often considered distasteful if cold, and vice versa.
Some sugar substitutes have strong heats of solution, as is the case of sorbitol, erythritol, xylitol, mannitol, lactitol, and maltitol. When they are dry and are allowed to dissolve in saliva, heat effects can be recognized. The cooling effect upon eating may be desirable, as in a mint candy made with crystalline sorbitol, or undesirable if it's not typical for that product, like in a cookie. Crystalline phases tend to have a positive heat of solution and thus a cooling effect. The heats of solution of the amorphous phases of the same substances are negative and cause a warm impression in the mouth.
# Supertasters
A supertaster is a person whose sense of taste is significantly more sharp than average. Women are more likely to be supertasters, as are Asians, Africans, and South Americans. Among individuals of European descent, it is estimated that about 25% of the population are supertasters. The cause of this heightened response is currently unknown, although it is thought to be, at least in part, due to an increased number of fungiform papillae. The evolutionary advantage to supertasting is unclear. In some environments, heightened taste response, particularly to bitterness, would represent an important advantage in avoiding potentially toxic plant alkaloids. However, in other environments, increased response to bitter may have limited the range of palatable foods. In a modern, energy-rich environment, supertasting may be cardioprotective, due to decreased liking and intake of fat, but may increase cancer risk via decreased vegetable intake. It may be a cause of picky eating, but picky eaters are not necessarily supertasters, and vice versa.
# Aftertaste
Aftertaste is the persistence of a sensation of flavor after the stimulating substance has passed out of contact with the sensory end organs for taste. Some aftertastes may be pleasant, others unpleasant.
Alcoholic beverages such as wine, beer and whiskey are noted for having particularly strong aftertastes. Foods with notable aftertastes include spicy foods, such as Mexican food (e.g. chili pepper), or Indian food (such as curry).
Medicines and tablets may also have a lingering aftertaste.
# Acquired taste
An acquired taste is an appreciation for a food or beverage that is unlikely to be enjoyed, in part or in full, by a person who has not had substantial exposure to it, usually because of some unfamiliar aspect of the food or beverage, including a strong or strange odor, taste, or appearance. The process of “acquiring” a taste involves consuming a food or beverage in the hope of learning to enjoy it. In most cases, this introductory period is considered worthwhile, as many of the world's delicacies are considered to be acquired tastes. A connoisseur is one who is held to have an expert judgment of taste.
# Factors affecting taste perception
Many factors affect taste perception, including:
- Aging
- Color/vision impairments
- Hormonal influences
- Genetic variations; see Phenylthiocarbamide
- Oral temperature
- Drugs and chemicals
- CNS Tumors (esp. Temporal lobe lesions) and other neurological causes
- Plugged noses
- Zinc deficiency
It is also important to consider that flavor is the overall, total sensation induced during mastication (e.g. taste, touch, pain and smell). Smell (olfactory stimulation) plays a major role in flavor perception.
# Disorders of taste
- ageusia (complete loss) | Taste
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
# Overview
Taste (or, more formally, gustation) is a form of direct chemoreception and is one of the traditional five senses. It refers to the ability to detect the flavor of substances such as food and poisons. In humans and many other vertebrate animals the sense of taste partners with the less direct sense of smell, in the brain's perception of flavor. In the West, experts traditionally identified four taste sensations: sweet, salty, sour, and bitter. Eastern experts traditionally identified a fifth, called umami. More recently, psychophysicists and neuroscientists have suggested other taste categories (umami and fatty acid taste most prominently, as well as the sensation of metallic and water tastes, although the latter is commonly disregarded due to the phenomenon of taste adaptation.)
Taste is a sensory function of the central nervous system. The receptor cells for taste in humans are found on the surface of the tongue, along the soft palate, and in the epithelium of the pharynx and epiglottis.
# Basic taste
Psychophysicists have long suggested the existence of four taste 'primaries', referred to as the basic tastes: sweetness, bitterness, sourness, and saltiness. Umami is now accepted as the fifth basic taste, exemplified by the non-salty sensations evoked by some free amino acids such as monosodium glutamate.[1][2][3]
Other possible categories have been suggested, such as a taste exemplified by certain fatty acids such as linoleic acid.[4][5][6] Some researchers still argue against the notion of primaries at all and instead favor a continuum of percepts [7][8][9], similar to color vision.
All of these taste sensations arise from all regions of the oral cavity, despite the common misconception of a "taste map" of sensitivity to different tastes thought to correspond to specific areas of the tongue.[10] This myth is generally attributed to the mis-translation of a German text, and perpetuated in North American schools since the early twentieth century [11]. Very slight regional differences in sensitivity to compounds exist, though these regional differences are subtle and do not conform exactly to the mythical tongue map. Individual taste buds (which contain approximately 100 taste receptor cells), in fact, typically respond to compounds evoking each of the five basic tastes.
The basic tastes are those commonly recognized types of taste sensed by humans. Humans receive tastes through sensory organs called taste buds or gustatory calyculi, concentrated on the upper surface of the tongue, but a few are also found on the roof of ones mouth furthering the taste sensations we can receive. Scientists describe five basic tastes: bitter, salty, sour, sweet, and umami (described as savory, meaty, or brothy). The basic tastes are only one component that contributes to the sensation of food in the mouth—other factors include the food's smell, detected by the olfactory epithelium of the nose, its texture, detected by mechanoreceptors, and its temperature, detected by thermoreceptors. Taste and smell are subsumed under the term flavor.
## History
In Western culture, the concept of basic tastes can be traced back at least to Aristotle, who cited "sweet" and "bitter", with "succulent", "salt", "pungent", "harsh", "puckery", and "sour" as elaborations of those two basics. The ancient Chinese Five Elements philosophy lists slightly different five basic tastes: bitter, salty, sour, sweet, and spicy. Japanese and Indian cultures each add their own sixth taste to the basic five.
For many years, books on the physiology of human taste contained diagrams of the tongue showing levels of sensitivity to different tastes in different regions. In fact, taste qualities are found in all areas of the tongue, in contrast with the popular view that different tastes map to different areas of the tongue.[12][13]
## Recent discoveries
The receptors for all known basic tastes have been identified. The receptors for sour and salty are ion channels while the receptors for sweet, bitter, and umami belong to the class of G protein coupled receptors.
In November 2005, a team of French researchers experimenting on rodents claimed to have evidence for a sixth taste, for fatty substances.[14] It is speculated that humans may also have the same receptors.[15] Fat has occasionally been raised as a possible basic taste in the past (Bravo 1592, Linnaeus 1751) but later classifications abandoned fat as a separate taste (Haller 1751 and 1763).
[16]
Meanwhile, scientists from the Monell Chemical Senses Center continue to research the five basic tastes, especially Umami.
# Five basic tastes
For a long period, it has been commonly accepted that there are a finite number of "basic tastes" by which all foods and tastes can be grouped. Just like with primary colors, these "basic tastes" only apply to the human perception, ie. the different sorts of tastes our tongue can identify. Up until the 2000s, this was considered to be a group of four basic tastes. More recently, a fifth taste, Umami, was added by a wide number of authorities in this field.[17]
### Bitterness
The bitter taste is perceived by many to be unpleasant, sharp, or disagreeable. Common bitter foods and beverages include coffee, unsweetened chocolate, bitter melon, beer, uncured olives, citrus peel, many plants in the Brassicaceae family, dandelion greens and escarole. Quinine is also known for its bitter taste and is found in tonic water.
The most bitter substance known is the synthetic chemical denatonium. It is used as an aversive agent that is added to toxic substances to prevent accidental ingestion. This was discovered in 1958 during research on lignocaine, a local anesthetic, by Macfarlan Smith of Edinburgh, Scotland.
Research has shown that TAS2Rs (taste receptors, type 2, also known as T2Rs) such as TAS2R38 coupled to the G protein gustducin are responsible for the human ability to taste bitter substances. They are identified not only by their ability to taste for certain "bitter" ligands, but also by the morphology of the receptor itself (surface bound, monomeric).[18] Researchers use two synthetic substances, phenylthiocarbamide (PTC) and 6-n-propylthiouracil (PROP) to study the genetics of bitter perception. These two substances taste bitter to some people, but are virtually tasteless to others. Among the tasters, some are so-called "supertasters" to whom PTC and PROP are extremely bitter. This genetic variation in the ability to taste a substance has been a source of great interest to those who study genetics. In addition, it is of interest to those who study evolution since PTC-tasting is associated with the ability to taste numerous natural bitter compounds, a large number of which are known to be toxic.
### Saltiness
Saltiness is a taste produced primarily by the presence of sodium ions. Other ions of the alkali metals group also taste salty. However the further from sodium the less salty is the sensation. The size of lithium and potassium ions most closely resemble those of sodium and thus the saltiness is most similar. In contrast rubidium and cesium ions are far larger so their salty taste differs accordingly. Potassium, as potassium chloride - KCl, is the principle ingredient in salt substitutes.
Other monovalent cations, e.g. ammonium, NH4+, and divalent cations of the alkali earth metal group of the periodic table, e.g. calcium, Ca2+, ions generally elicit a bitter rather than a salty taste even though they too can pass directly through ion channels in the tongue, generating an action potential.
### Sourness
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Sourness is the taste that detects acidity. The mechanism for detecting sour taste is similar to that which detects salt taste. Hydrogen ion channels detect the concentration of hydronium ions (H3O+ ions) that are formed from acids and water.
Hydrogen ions are capable of permeating the amiloride-sensitive channels, but this is not the only mechanism involved in detecting the quality of sourness. Other channels have also been proposed in the literature. Hydrogen ions also inhibit the potassium channel, which normally functions to hyperpolarize the cell. By a combination of direct intake of hydrogen ions (which itself depolarizes the cell) and the inhibition of the hyperpolarizing channel, sourness causes the taste cell to fire in this specific manner. In addition, it has also been suggested that weak acids, such as CO2 which is converted into the bicarbonate ion HCO3– by the enzyme carbonic anhydrase, to mediate weak acid transport.Template:Unclear
### Sweetness
Sweetness is produced by the presence of sugars, some proteins and a few other substances. Sweetness is often connected to aldehydes and ketones, which contain a carbonyl group. Sweetness is detected by a variety of G protein coupled receptors coupled to the G protein gustducin found on the taste buds. At least two different variants of the "sweetness receptors" need to be activated for the brain to register sweetness. The compounds which the brain senses as sweet are thus compounds that can bind with varying bond strength to two different sweetness receptors. These receptors are T1R2+3 (heterodimer) and T1R3 (homodimer), which are shown to be accountable for all sweet sensing in humans and animals.[19] The average human detection threshold for sucrose is 10 millimoles per litre. For lactose it is 30 millimoles per litre, and 5-Nitro-2-propoxyaniline 0.002 millimoles per litre.
Template:Seealso
### Umami
Template:Nihongo is the name for the taste sensation produced by compounds such as glutamate, and are commonly found in fermented and aged foods. In English, it is also described as "meatiness", "relish", or "savoriness". The Japanese word comes from Template:Nihongo for yummy, keen, or nice. Umami is now the commonly used term by taste scientists. The same taste is referred to as xiānwèi (Template:Nihongo2 or Template:Nihongo2) in Chinese cooking. Umami is considered a fundamental taste in Chinese and Japanese cooking, but is not discussed as much in Western cuisine.
Humans have taste receptors specifically for the detection of the amino acids, e.g. glutamic acid. Amino acids are commonly found in meats, cheese, fish, and other protein-heavy foods. Examples of food containing glutamate (and thus strong in umami) are beef, lamb, parmesan and roquefort cheese as well as soy sauce and fish sauce. The glutamate taste sensation is most intense in combination with sodium ions, as found in table salt. Sauces with umami and salty tastes are very popular for cooking, such as worcestershire sauce for Western cuisines and soy sauce and fish sauce for Asian cuisines.
The additive monosodium glutamate (MSG), which was developed as a food additive in 1907 by Kikunae Ikeda, produces a strong umami. Umami is also provided by the nucleotides 5’-inosine monophosphate (IMP) and 5’-guanosine monophosphate (GMP). These are naturally present in many protein-rich foods. IMP is present in high concentrations in many foods, including dried skipjack tuna flakes used to make dashi, a Japanese broth. GMP is present in high concentration in dried shiitake mushrooms, used in much of the cuisine of Asia. There is a synergistic effect between MSG, IMP, and GMP which together in certain ratios produce a strong umami.
Some umami taste buds respond specifically to glutamate in the same way that sweet ones respond to sugar. Glutamate binds to a variant of G protein coupled glutamate receptors.[20][21]
### Fattiness?
Recent research has revealed a potential taste receptor called the CD36 receptor to be reacting to fat, more specifically, fatty acids.[22] This receptor was found in mice, but probably exists among other mammals as well. In experiments, mice with a genetic defect that blocked this receptor didn't show the same urge to consume fatty acids as normal mice, and failed to prepare gastric juices in their digestive tracts to digest fat. This discovery may lead to a better understanding of the biochemical reasons behind this behaviour, although more research is still necessary to confirm the relationship between CD36 and the perception of fat.
# Further sensations
The tongue can also feel other sensations, not generally called tastes per se or included in the five human tastes. These are largely detected by the somatosensory system.
## Dryness
Some foods, such as unripe fruits, contain tannins or calcium oxalate that cause an astringent or rough sensation of the mucous membrane of the mouth or the teeth. Examples include tea, rhubarb, grapes and unripe persimmons and bananas.
Less exact terms for the astringent sensation are "dry", "rough", "harsh" (especially for wine), "tart", (normally referring to sourness) "rubbery", "hard", or "styptic",[23]. The Chinese have a term for this: 澀 (sè), the Koreans have 떫다 (tteolda), the Japanese call it 渋い (shibui), while Thai have ฝาด (fard), the Malay use kelat, Filipinos use pakla, and in Russian there is вяжущий (vyazhuschiy) or тёрпкий (tjorpky).
In the Indian tradition, one of the 6 tastes (sweet, sour, salty, bitter, hot/pungent and dry) [2] is astringency (Kasaaya in Sanskrit). This is more or less in line with the Japanese approach to umami.
## Metallicness
Most people know this taste (e.g. Cu2+, FeSO4, or blood in mouth), but it is not only taste but olfactory receptors worked in this case (Guth and Grosch, 1990). Metallic taste is commonly known, however biologists are reluctant to categorize it with the other taste sensations. One of the primary reasons is that it is not one commonly associated with consumption of food. Proponents of the theory contest that the sensation is readily detectable and distinguishable to test subjects. Therefore, metallic should be added as one of the basic types of sensations in the chemical receptor senses.
## Prickliness or hotness
Substances such as ethanol and capsaicin cause a burning sensation by inducing a trigeminal nerve reaction together with normal taste reception. The sensation of heat is caused by the food activating a nerve cell called TRP-V1, which is also activated by hot temperatures. The piquant sensation, usually referred to as being "hot" or "spicy", is a notable feature of Mexican, Hungarian, Indian, Szechuan, Korean, Indonesian, central Vietnamese, and Thai cuisines.
The two main plants providing this sensation are chili peppers (those fruits of the Capsicum plant that contain capsaicin) and black pepper.
If tissue in the oral cavity has been damaged or sensitised, ethanol may be experienced as pain rather than simply heat. Those who have had radiotherapy for oral cancer thus find it painful to drink alcohol.
In many cases, this particular sensation is not considered a taste, so much as a painful reaction to certain marginally damaging chemicals on the taste receptors and the skin of the tongue. While the taste nerves are activated when consuming foods like chili peppers, the reaction commonly interpreted as "hot" is derived from the tongue's pain nerves firing.
## Coolness
Some substances activate cold trigeminal receptors. One can sense a cool sensation (also known as "fresh" or "minty") from, e.g., spearmint, menthol, ethanol or camphor, which is caused by the food activating the TRP-M8 ion channel on nerve cells that also signal cold. Unlike the actual change in temperature described for sugar substitutes, coolness is only a perceived phenomenon.
## Numbness
Both Chinese and Batak Toba cooking include the idea of 麻 má, or mati rasa the sensation of tingling numbness caused by spices such as Sichuan pepper. The cuisine of Sichuan province in China and of North Sumatra province in Indonesia, often combines this with chili pepper to produce a 麻辣 málà, "numbing-and-hot", or "mati rasa" flavor.[24]
## Heartiness (Kokumi)
Some Japanese researchers refer to the kokumi in foods laden with alcohol- and thiol-groups in their amino acid extracts which has been described variously as continuity, mouthfulness, mouthfeel, and thickness.
## Temperature
Temperature is an essential element of human taste experience. Food and drink that—within a given culture—is considered to be properly served hot is often considered distasteful if cold, and vice versa.
Some sugar substitutes have strong heats of solution, as is the case of sorbitol, erythritol, xylitol, mannitol, lactitol, and maltitol. When they are dry and are allowed to dissolve in saliva, heat effects can be recognized. The cooling effect upon eating may be desirable, as in a mint candy made with crystalline sorbitol, or undesirable if it's not typical for that product, like in a cookie. Crystalline phases tend to have a positive heat of solution and thus a cooling effect. The heats of solution of the amorphous phases of the same substances are negative and cause a warm impression in the mouth.[25]
# Supertasters
A supertaster is a person whose sense of taste is significantly more sharp than average. Women are more likely to be supertasters, as are Asians, Africans, and South Americans. Among individuals of European descent, it is estimated that about 25% of the population are supertasters. The cause of this heightened response is currently unknown, although it is thought to be, at least in part, due to an increased number of fungiform papillae.[26] The evolutionary advantage to supertasting is unclear. In some environments, heightened taste response, particularly to bitterness, would represent an important advantage in avoiding potentially toxic plant alkaloids. However, in other environments, increased response to bitter may have limited the range of palatable foods. In a modern, energy-rich environment, supertasting may be cardioprotective, due to decreased liking and intake of fat, but may increase cancer risk via decreased vegetable intake. It may be a cause of picky eating, but picky eaters are not necessarily supertasters, and vice versa.
# Aftertaste
Aftertaste is the persistence of a sensation of flavor after the stimulating substance has passed out of contact with the sensory end organs for taste. Some aftertastes may be pleasant, others unpleasant.
Alcoholic beverages such as wine, beer and whiskey are noted for having particularly strong aftertastes. Foods with notable aftertastes include spicy foods, such as Mexican food (e.g. chili pepper), or Indian food (such as curry).
Medicines and tablets may also have a lingering aftertaste.
# Acquired taste
An acquired taste is an appreciation for a food or beverage that is unlikely to be enjoyed, in part or in full, by a person who has not had substantial exposure to it, usually because of some unfamiliar aspect of the food or beverage, including a strong or strange odor, taste, or appearance. The process of “acquiring” a taste involves consuming a food or beverage in the hope of learning to enjoy it. In most cases, this introductory period is considered worthwhile, as many of the world's delicacies are considered to be acquired tastes. A connoisseur is one who is held to have an expert judgment of taste.
# Factors affecting taste perception
Many factors affect taste perception, including:
- Aging
- Color/vision impairments
- Hormonal influences
- Genetic variations; see Phenylthiocarbamide
- Oral temperature
- Drugs and chemicals
- CNS Tumors (esp. Temporal lobe lesions) and other neurological causes[27]
- Plugged noses
- Zinc deficiency
It is also important to consider that flavor is the overall, total sensation induced during mastication (e.g. taste, touch, pain and smell). Smell (olfactory stimulation) plays a major role in flavor perception.
# Disorders of taste
- ageusia (complete loss) | https://www.wikidoc.org/index.php/Basic_taste | |
db4c204485cff6d9b851b0b2e18edd66f09685a3 | wikidoc | Basil | Basil
Basil (Ocimum basilicum) (Template:IPAEng or Template:IPA), of the Family Lamiaceae. Basil is a tender low-growing herb that is grown as a perennial in warm, tropical climates. Basil is originally native to India and other tropical regions of Asia, having been cultivated there for more than 5,000 years. There are many varieties of basil, that which is used in Italian food is typically called sweet basil, as opposed to Thai basil or holy basil, which are used in Asia. It is prominently featured in Italian cuisine, and also plays a major role in the Southeast Asian cuisines of Thai, Vietnamese and Laotian. It grows to between 30–60 cm tall, with opposite, light green, silky leaves 3–5 cm long and 1–3 cm broad. The flowers are quite big, white in color and arranged in a terminal spike. Unusual among Lamiaceae, the four stamens and the pistil are not pushed under the upper lip of the corolla, but lay over the inferior. After entomophilous pollination, the corolla falls off and four round achenes develop inside the bilabiate calyx. The plant tastes somewhat like anise, with a strong, pungent, sweet smell. Basil is very sensitive to cold, with best growth in hot, dry conditions. While most common varieties are treated as annuals, some are perennial, including African Blue and Holy Thai basil.
The word basil comes from the Greek βασιλεύς (basileus), meaning "king", as it is believed to have grown above the spot where St. Constantine and Helen discovered the Holy Cross. The Oxford English Dictionary quotes speculations that basil may have been used in "some royal unguent, bath, or medicine". Basil is still considered the "king of herbs" by many cookery authors. An alternative etymology has "basil" coming from the Latin word basilicus, meaning dragon and being the root for basilisk, but this likely was a linguistic reworking of the word as brought from Greece.
# Culinary use
Basil is most commonly recommended to be used fresh; in cooked recipes it is generally added at the last moment, as cooking quickly destroys the flavour. The fresh herb can be kept for a short time in plastic bags in the refrigerator, or for a longer period in the freezer, after being blanched quickly in boiling water. The dried herb also loses most of its flavour, and what little flavour remains tastes very different, with a weak coumarin flavour, like hay.
Basil is one of the main ingredients in pesto—a green Italian oil-and-herb sauce from the city of Genoa, its other two main ingredients being olive oil and pine nuts. The most commonly used Mediterranean basil cultivars are "Genovese", "Purple Ruffles", "Mammoth", "Cinnamon", "Lemon", "Globe", and "African Blue". Chinese also use fresh or dried basils in soups and other foods. In Taiwan, people add fresh basil leaves into thick soups (羹湯; gēngtāng). They also eat fried chicken with deep-fried basil leaves.
Basil is sometimes used with fresh fruit and in fruit jams and sauces—in particular with strawberries, but also raspberries or dark-colored plums. Arguably the flat-leaf basil used in Vietnamese cooking, which has a slightly different flavour, is more suitable for use with fruit.
## Basil seeds
When soaked in water the seeds of several basil varieties become gelatinous, and are used in Asian drinks and desserts such as falooda or sherbet. Such seeds are known variously as sabja, subja, takmaria, tukmaria, falooda, or hột é. They are used for their medicinal properties in Ayurveda, the traditional medicinal system of India.
# Other basils
Several other basils, including some other Ocimum species, are grown in many regions of Asia. Most of the Asian basils have a clove-like flavour that is generally stronger than the Mediterranean basils. The most notable is the holy basil or tulsi (Tamil: கி௫ஷ்ண துளசி), a revered home-grown plant in India. In China, the local cultivar is called 九層塔 (jiǔ-kéng-tǎ; literally "nine-level pagoda"), while the imported varieties are specifically called 羅勒 (luó-lè) or 巴西里 (bā-xī-lǐ), although often refers to another different kind plant--parsley.
Lemon basil has a strong lemony smell and flavour very different from those of other varieties because it contains a chemical called citral. It is widely used in Indonesia, where it is called kemangi and served raw, together with raw cabbage, green beans, and cucumber, as an accompaniment to fried fish or duck. Its flowers, broken up, are a zesty salad condiment.
# Chemical components
The various basils have such different scents because the herb has a number of different essential oils which come together in different proportions for various breeds. The strong clove scent of sweet basil comes from eugenol, the same chemical as actual cloves. The citrus scent of lemon basil and lime basil is because they have a higher portion of citral which causes this effect in several plants, including lemon mint, and limonene, which gives actual lemon peel its scent. African blue basil has a strong camphor smell because it has camphor and camphene in higher proportions. Licorice Basil contains anethole, the same chemical that makes anise smell like licorice, and in fact is sometimes called Anise Basil.
Other chemicals helping produce the distinctive scents of many basils, depending on their proportion in each specific breed, including:
- cinnamate (same as in cinnamon)
- citronellol (geraniums, roses, and citronella)
- geraniol (as in geranium)
- linalool (a flowery scent also in coriander)
- methyl chavicol (which gives tarragon its scent)
- myrcene (bay, myrcia)
- pinene (which is, as the name implies, the chemical which gives pine oil its scent)
- ocimene
- terpineol
# Cultivation
Basil thrives in hot weather, but behaves as an annual if there is any chance of a frost. In Northern Europe, the northern states of the U.S., and the South Island of New Zealand it will grow best if sown under glass in a peat pot, then planted out in late spring/early summer (when there is little chance of a frost). It fares best in a well-drained sunny spot.
Although basil will grow best outdoors, it can be grown indoors in a pot and, like most herbs, will do best on an equator-facing windowsill. It should be kept away from extremely cold drafts, and grows best in strong sunlight, therefore a greenhouse or Row cover is ideal if available. They can, however, be grown even in a basement, under fluorescent lights.
If its leaves have wilted from lack of water, it will recover if watered thoroughly and placed in a sunny location. Yellow leaves towards the bottom of the plant are an indication that the plant needs more sunlight or less fertilizer.
In sunnier climates such as Southern Europe, the southern states of the U.S., the North Island of New Zealand, and Australia, basil will thrive when planted outside. It also thrives over the summertime in the central and northern United States, but dies out when temperatures reach freezing point, to grow again the next year if allowed to go to seed. It will need regular watering, but not as much attention as is needed in other climates.
Basil can also be propagated very reliably from cuttings in exactly the same manner as Busy Lizzie (Impatiens), with the stems of short cuttings suspended for two weeks or so in water until roots develop.
If a stem successfully produces mature flowers, leaf production slows or stops on any stem which flowers, the stem becomes woody, and essential oil production declines.To prevent this, a basil-grower may pinch off any flower stems before they are fully mature. Because only the blooming stem is so affected, some can be pinched for leaf production, while others are left to bloom for decoration or seeds.
Once the plant is allowed to flower, it may produce seed pods containing small black seeds which can be saved and planted the following year. Picking the leaves off the plant helps "promote growth", largely because the plant responds by converting pairs of leaflets next to the topmost leaves into new stems.
## Diseases
Basil suffers from several plant pathogens that can ruin the crop and reduce yield. Fusarium wilt is a soilbourne fungal disease that will quickly kill younger basil plants. Seedlings may also be killed by Pythium damping off.
A common foliar disease of basil is gray mold caused by Botrytis cinerea, can also cause infections post-harvest and is capable of killing the entire plant. Black spot can also be seen on basil foliage and is caused by the fungi genus Colletotrichum.
# Health effects
Recently, there has been much research into the health benefits conferred by the essential oils found in basil. Scientific studies have established that compounds in basil oil have potent antioxidant hence anti-aging, anti-cancer, anti-viral, and anti-microbial properties. In addition, basil has been shown to decrease the occurrence of platelet aggregation and experimental thrombus in mice. It is therefore, traditionally used for supplementary treatment of stress, asthma and diabetes in India.
Basil, like other aromatic plants such as fennel and tarragon, contains estragole, a known carcinogen and teratogen in rats and mice. While human effects are currently unstudied, the rodent experiments indicate that it would take 100–1000 times the normal anticipated exposure to become a cancer risk.
# Cultural aspects
There are many rituals and beliefs associated with basil. The French call basil "l'herbe royale". Jewish folklore suggests it adds strength while fasting. It is a symbol of love in present-day Italy, but represented hatred in ancient Greece, and European lore sometimes claims that basil is a symbol of Satan. African legend claims that basil protects against scorpions, while the English botanist Culpeper cites one "Hilarius, a French physician" as affirming it as common knowledge that smelling basil too much would breed scorpions in the brain.
Holy Basil, also called 'Tulsi', is highly revered in Hinduism and also has religious significance in the Greek Orthodox Church, where it is used to prepare holy water. It is said to have been found around Christ's tomb after his resurrection. The Serbian Orthodox Church, Macedonian Orthodox Church and Romanian Orthodox Church use basil (Macedonian: босилек; Romanian: busuioc, Serbian: босиљак) to prepare holy water and pots of basil are often placed below church altars.
In Europe, they place basil in the hands of the dead to ensure a safe journey. In India, they place it in the mouth of the dying to ensure they reach God. The ancient Egyptians and ancient Greeks believed that it would open the gates of heaven for a person passing on.
In Boccaccio's Decameron a memorably morbid tale (novella V) tells of Lisabetta, whose brothers slay her lover. He appears to her in a dream and shows her where he is buried. She secretly disinters the head, and sets it in a pot of basil, which she waters with her daily tears. The pot being taken from her by her brothers, she dies of her grief not long after. Boccaccio's tale is the source of John Keats' poem Isabella or The Pot of Basil. A similar story is told of the Longobard queen Rosalind. | Basil
Basil (Ocimum basilicum) (Template:IPAEng or Template:IPA), of the Family Lamiaceae. Basil is a tender low-growing herb that is grown as a perennial in warm, tropical climates. Basil is originally native to India and other tropical regions of Asia, having been cultivated there for more than 5,000 years. There are many varieties of basil, that which is used in Italian food is typically called sweet basil, as opposed to Thai basil or holy basil, which are used in Asia. It is prominently featured in Italian cuisine, and also plays a major role in the Southeast Asian cuisines of Thai, Vietnamese and Laotian. It grows to between 30–60 cm tall, with opposite, light green, silky leaves 3–5 cm long and 1–3 cm broad. The flowers are quite big, white in color and arranged in a terminal spike. Unusual among Lamiaceae, the four stamens and the pistil are not pushed under the upper lip of the corolla, but lay over the inferior. After entomophilous pollination, the corolla falls off and four round achenes develop inside the bilabiate calyx. The plant tastes somewhat like anise, with a strong, pungent, sweet smell. Basil is very sensitive to cold, with best growth in hot, dry conditions. While most common varieties are treated as annuals, some are perennial, including African Blue and Holy Thai basil.
The word basil comes from the Greek βασιλεύς (basileus), meaning "king", as it is believed to have grown above the spot where St. Constantine and Helen discovered the Holy Cross. The Oxford English Dictionary quotes speculations that basil may have been used in "some royal unguent, bath, or medicine". Basil is still considered the "king of herbs" by many cookery authors. An alternative etymology has "basil" coming from the Latin word basilicus, meaning dragon and being the root for basilisk, but this likely was a linguistic reworking of the word as brought from Greece.
# Culinary use
Basil is most commonly recommended to be used fresh; in cooked recipes it is generally added at the last moment, as cooking quickly destroys the flavour. The fresh herb can be kept for a short time in plastic bags in the refrigerator, or for a longer period in the freezer, after being blanched quickly in boiling water. The dried herb also loses most of its flavour, and what little flavour remains tastes very different, with a weak coumarin flavour, like hay.
Basil is one of the main ingredients in pesto—a green Italian oil-and-herb sauce from the city of Genoa, its other two main ingredients being olive oil and pine nuts. The most commonly used Mediterranean basil cultivars are "Genovese", "Purple Ruffles", "Mammoth", "Cinnamon", "Lemon", "Globe", and "African Blue". Chinese also use fresh or dried basils in soups and other foods. In Taiwan, people add fresh basil leaves into thick soups (羹湯; gēngtāng). They also eat fried chicken with deep-fried basil leaves.
Basil is sometimes used with fresh fruit and in fruit jams and sauces—in particular with strawberries, but also raspberries or dark-colored plums. Arguably the flat-leaf basil used in Vietnamese cooking, which has a slightly different flavour, is more suitable for use with fruit.
## Basil seeds
When soaked in water the seeds of several basil varieties become gelatinous, and are used in Asian drinks and desserts such as falooda or sherbet. Such seeds are known variously as sabja, subja, takmaria, tukmaria, falooda, or hột é. They are used for their medicinal properties in Ayurveda, the traditional medicinal system of India.
# Other basils
Several other basils, including some other Ocimum species, are grown in many regions of Asia. Most of the Asian basils have a clove-like flavour that is generally stronger than the Mediterranean basils. The most notable is the holy basil or tulsi (Tamil: கி௫ஷ்ண துளசி), a revered home-grown plant in India. In China, the local cultivar is called 九層塔 (jiǔ-kéng-tǎ; literally "nine-level pagoda"), while the imported varieties are specifically called 羅勒 (luó-lè) or 巴西里 (bā-xī-lǐ), although [巴西里] often refers to another different kind plant--parsley.
Lemon basil has a strong lemony smell and flavour very different from those of other varieties because it contains a chemical called citral. It is widely used in Indonesia, where it is called kemangi and served raw, together with raw cabbage, green beans, and cucumber, as an accompaniment to fried fish or duck. Its flowers, broken up, are a zesty salad condiment.
# Chemical components
The various basils have such different scents because the herb has a number of different essential oils which come together in different proportions for various breeds. The strong clove scent of sweet basil comes from eugenol, the same chemical as actual cloves. The citrus scent of lemon basil and lime basil is because they have a higher portion of citral which causes this effect in several plants, including lemon mint, and limonene, which gives actual lemon peel its scent. African blue basil has a strong camphor smell because it has camphor and camphene in higher proportions. Licorice Basil contains anethole, the same chemical that makes anise smell like licorice, and in fact is sometimes called Anise Basil.
Other chemicals helping produce the distinctive scents of many basils, depending on their proportion in each specific breed, including:
- cinnamate (same as in cinnamon)
- citronellol (geraniums, roses, and citronella)
- geraniol (as in geranium)
- linalool[1] (a flowery scent also in coriander)
- methyl chavicol[1] (which gives tarragon its scent)
- myrcene (bay, myrcia)
- pinene (which is, as the name implies, the chemical which gives pine oil its scent)
- ocimene
- terpineol
# Cultivation
Basil thrives in hot weather, but behaves as an annual if there is any chance of a frost. In Northern Europe, the northern states of the U.S., and the South Island of New Zealand it will grow best if sown under glass in a peat pot, then planted out in late spring/early summer (when there is little chance of a frost). It fares best in a well-drained sunny spot.
Although basil will grow best outdoors, it can be grown indoors in a pot and, like most herbs, will do best on an equator-facing windowsill. It should be kept away from extremely cold drafts, and grows best in strong sunlight, therefore a greenhouse or Row cover is ideal if available. They can, however, be grown even in a basement, under fluorescent lights.
If its leaves have wilted from lack of water, it will recover if watered thoroughly and placed in a sunny location. Yellow leaves towards the bottom of the plant are an indication that the plant needs more sunlight or less fertilizer.
In sunnier climates such as Southern Europe, the southern states of the U.S., the North Island of New Zealand, and Australia, basil will thrive when planted outside. It also thrives over the summertime in the central and northern United States, but dies out when temperatures reach freezing point, to grow again the next year if allowed to go to seed. It will need regular watering, but not as much attention as is needed in other climates.
Basil can also be propagated very reliably from cuttings in exactly the same manner as Busy Lizzie (Impatiens), with the stems of short cuttings suspended for two weeks or so in water until roots develop.
If a stem successfully produces mature flowers, leaf production slows or stops on any stem which flowers, the stem becomes woody, and essential oil production declines.To prevent this, a basil-grower may pinch off any flower stems before they are fully mature. Because only the blooming stem is so affected, some can be pinched for leaf production, while others are left to bloom for decoration or seeds.
Once the plant is allowed to flower, it may produce seed pods containing small black seeds which can be saved and planted the following year. Picking the leaves off the plant helps "promote growth", largely because the plant responds by converting pairs of leaflets next to the topmost leaves into new stems.
## Diseases
Basil suffers from several plant pathogens that can ruin the crop and reduce yield. Fusarium wilt is a soilbourne fungal disease that will quickly kill younger basil plants. Seedlings may also be killed by Pythium damping off.
A common foliar disease of basil is gray mold caused by Botrytis cinerea, can also cause infections post-harvest and is capable of killing the entire plant. Black spot can also be seen on basil foliage and is caused by the fungi genus Colletotrichum.
# Health effects
Recently, there has been much research into the health benefits conferred by the essential oils found in basil. Scientific studies have established that compounds in basil oil have potent antioxidant hence anti-aging, anti-cancer, anti-viral, and anti-microbial properties.[2][3][4][5] In addition, basil has been shown to decrease the occurrence of platelet aggregation and experimental thrombus in mice.[6] It is therefore, traditionally used for supplementary treatment of stress, asthma and diabetes in India.[7]
Basil, like other aromatic plants such as fennel and tarragon, contains estragole, a known carcinogen and teratogen in rats and mice. While human effects are currently unstudied, the rodent experiments indicate that it would take 100–1000 times the normal anticipated exposure to become a cancer risk.[8]
# Cultural aspects
There are many rituals and beliefs associated with basil. The French call basil "l'herbe royale". Jewish folklore suggests it adds strength while fasting. It is a symbol of love in present-day Italy, but represented hatred in ancient Greece, and European lore sometimes claims that basil is a symbol of Satan. African legend claims that basil protects against scorpions, while the English botanist Culpeper cites one "Hilarius, a French physician" as affirming it as common knowledge that smelling basil too much would breed scorpions in the brain.
Holy Basil, also called 'Tulsi', is highly revered in Hinduism and also has religious significance in the Greek Orthodox Church, where it is used to prepare holy water. It is said to have been found around Christ's tomb after his resurrection. The Serbian Orthodox Church, Macedonian Orthodox Church and Romanian Orthodox Church use basil (Macedonian: босилек; Romanian: busuioc, Serbian: босиљак) to prepare holy water and pots of basil are often placed below church altars.
In Europe, they place basil in the hands of the dead to ensure a safe journey. In India, they place it in the mouth of the dying to ensure they reach God. The ancient Egyptians and ancient Greeks believed that it would open the gates of heaven for a person passing on.
In Boccaccio's Decameron a memorably morbid tale (novella V) tells of Lisabetta, whose brothers slay her lover. He appears to her in a dream and shows her where he is buried. She secretly disinters the head, and sets it in a pot of basil, which she waters with her daily tears. The pot being taken from her by her brothers, she dies of her grief not long after. Boccaccio's tale is the source of John Keats' poem Isabella or The Pot of Basil. A similar story is told of the Longobard queen Rosalind. | https://www.wikidoc.org/index.php/Basil | |
0898a593cc29bbde20d1dc0493675962adf71df0 | wikidoc | Rales | Rales
Synonyms and keywords: Crackles; crepitations
# Overview
Rales are the clicking, rattling, or crackling noises heard on auscultation of (listening to) the lung with a stethoscope during inhalation. The sounds are caused by the "popping open" of small airways and alveoli collapsed by fluid, exudate, or lack of aeration during expiration. The word "rales" derives from the French word râle meaning "rattle".
# Causes
## Common Causes
- Atelectasis
- Bronchiectasis
- Bronchitis, acute
- Congestive heart failure
- Pneumonia
- Pulmonary edema
- Pulmonary fibrosis
# Diagnosis
## Physical Examination
### The Sound of Rales
Crackles (or rales) are caused by explosive opening of small airways. Cracklinuous sounds; they are intermittent, nonmusical and brief. Crackles are much more common during the inspiratory than the expiratory phase of breathing, but they may be heard during the expiratory phase. Crackles are often associated with inflammation or infection of the small bronchi, bronchioles, and alveoli. Crackles that don't clear after a cough may indicate pulmonary edema or fluid in the alveoli due to heart failure or acute respiratory distress syndrome.
- Crackles are often described as fine, medium, and coarse. They can also be characterized as to their timing: fine crackles are usually late-inspiratory, whereas coarse crackles are early inspiratory.
- Fine crackles are soft, high-pitched, and very brief. This sound can be simulated by rolling a strand of hair between one's fingers near the ears, or by moistening one's thumb and index finger and separating them near the ears. Their presence usually indicates an interstitial process, such as pulmonary fibrosis or congestive heart failure.
- Coarse crackles are somewhat louder, lower in pitch, and last longer than fine crackles. They have been described as sounding like opening a Velcro fastener. Their presence usually indicates an airway disease, such as bronchiectasis.
# Related Chapters
- Wheeze
- Rhonchi
- Bronchophony
- Egophony | Rales
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Synonyms and keywords: Crackles; crepitations
# Overview
Rales are the clicking, rattling, or crackling noises heard on auscultation of (listening to) the lung with a stethoscope during inhalation. The sounds are caused by the "popping open" of small airways and alveoli collapsed by fluid, exudate, or lack of aeration during expiration. The word "rales" derives from the French word râle meaning "rattle".
# Causes
## Common Causes
- Atelectasis
- Bronchiectasis
- Bronchitis, acute
- Congestive heart failure
- Pneumonia
- Pulmonary edema
- Pulmonary fibrosis
# Diagnosis
## Physical Examination
### The Sound of Rales
Crackles (or rales) are caused by explosive opening of small airways. Cracklinuous sounds; they are intermittent, nonmusical and brief. Crackles are much more common during the inspiratory than the expiratory phase of breathing, but they may be heard during the expiratory phase. Crackles are often associated with inflammation or infection of the small bronchi, bronchioles, and alveoli. Crackles that don't clear after a cough may indicate pulmonary edema or fluid in the alveoli due to heart failure or acute respiratory distress syndrome.
- Crackles are often described as fine, medium, and coarse. They can also be characterized as to their timing: fine crackles are usually late-inspiratory, whereas coarse crackles are early inspiratory.
- Fine crackles are soft, high-pitched, and very brief. This sound can be simulated by rolling a strand of hair between one's fingers near the ears, or by moistening one's thumb and index finger and separating them near the ears. Their presence usually indicates an interstitial process, such as pulmonary fibrosis or congestive heart failure.
- Coarse crackles are somewhat louder, lower in pitch, and last longer than fine crackles. They have been described as sounding like opening a Velcro fastener. Their presence usually indicates an airway disease, such as bronchiectasis.
# Related Chapters
- Wheeze
- Rhonchi
- Bronchophony
- Egophony | https://www.wikidoc.org/index.php/Basilar_crackles | |
a44709c89d82d44f28330f8250ab6555f3bbe331 | wikidoc | Batyr | Batyr
Batyr was an Asian Elephant known for his ability to precisely reproduce human speech. Born in 1970, he lived his entire life in the Karaganda Zoo in Karaganda, Kazakhstan. He died in the spring of 1993 having never seen or heard another elephant. Batyr was the offspring of once-wild Indian Elephants (a subspecies of the Asian Elephant). Batyr's mother "Palm" and father "Dubas" had been presented to Kazakhstan's Almaty Zoo by Indian prime minister Jawaharlal Nehru.
Batyr, whose name was a Turkic word meaning The Dashing Equestrian, The Man of Courage or The Athlete, first made his surprising abilities known just before New Year's Day in the winter of 1977. Zoo employees were the first to notice his "speech", but he soon delighted zoo-goers at large by asking his attendants for water and regularly praising (or, infrequently chastising) himself. By 1979, his fame as the "Speaking Elephant" had spread in the wake of various mass-media stories about his abilities. (Many of these contained considerable fabrication and wild conjecture.) Batyr's case was also included in several books on animal behaviour, and in the proceedings of several scientific conferences. These developments drew a spate of zoo visitors, and brought the offer of an exchange—Batyr for a rare Dwarf Chimpanzee—from the Czechoslovak Circus; the offer was rejected by the zoo's employees.
A. N. Pogrebnoj-Aleksandroff, the doctor of sciences who studied Batyr's abilities and wrote many publications about him, said of the elephant:
«Batyr, on the level of natural blares, said the words (including a human slang) by manipulating a trunk. Having put the trunk in a mouth, pressing a tip of the trunk by the bottom of jaw and manipulating of tongue, said words. Besides, being in a corner of the cage (quite often at the nights) with the hanging down and weakened his trunk the elephant said words very silently — that sound is comparable with a sound of ultrasonic devices against mosquitoes or as peep of the mosquitoes, which human hearing well hears to approximately 40-year-old age. During pronouncing of words, only the tip of the trunk of the elephant has been clamped inside and Batyr made insignificant movements by a finger-shaped shoot on the trunk tip».
Various audiovisual recordings were made during Pogrebnoj-Aleksandroff's studies of Batyr;some of these have been transferred to Russia's Moscow State University for further study.
# Lexicon of the elephant Batyr
Batyr said about 20 words in Russian and Kazakh languages, imitated sounds of animals and said short phrases (even said words of human slang)
The full list of words and phrases which Batyr said:
- «Баты́р» — Batyr — abruptly (the trunk in the mouth);
- «Я» — I'm — very abruptly and to combination of his name, at a long pronunciation so «I'm-Batyr», sounded almost together;
- «Ба́ты́р» — Batyr — thoughtfully-tenderly and lingeringly (the trunk in the mouth);
- «Батыр, Батыр, Батыр…» — Batyr, Batyr, Batyr — joyfully running in a cage (the trunk in the mouth);
- «Воды́» — Water — ask (the trunk in the mouth);
- «Хоро́ший» — Good — as is good fellow (the trunk in the mouth);
- «Батыр хоро́ший» — Good Batyr — (the trunk in the mouth);
- «Ой-ё-ёй» — Oh-yo — (it is very sonorous — the trunk in the mouth);
- «Дурак» — The Fool — seldom and abruptly (the trunk in the mouth);
- «Плохой» — Bad — it is rare (the trunk in the mouth);
- «Батыр плохой» — Bad Batyr — it is rare (the trunk in the mouth);
- «Иди́» — Go — (the trunk in the mouth);
- «Иди (на) хуй» — Go onto penis (on-similarity the American expression 'fuck you') — the obscene russian slang; first and unique time during telecast shooting (the trunk in the mouth);
- «Хуй» — The russian slang of the penis — seldom and abruptly (the trunk in the mouth);
- «Ба́-ба» — the short of "babushka" — the grandmother; short children's sound "ba" (the trunk in the mouth);
- «Да́» — Yes — (the trunk in the mouth);
- «Дай» — Give (me) — (the trunk in the mouth);
- «Дай-дай-дай» — Give, give, give... — (the trunk in the mouth);
- «Раз-два-три» — One, two, three — dancing, being turned and hopping (the trunk in the mouth);
- A whistle of human;
- The words of human speech said at level of infrasonic and ultrasonic frequencies;
- A gnash imitation of rubber or polyfoam (foam plastic) on glass;
- The peep of rats or mice;
- The bark of dogs;
- The natural blares of elephants.
# From the press
"SOVIET ZOO HAS TALKING ELEPHANT written by Richard Beeston in Moscow, Batyr, a 10 year old indian elephant at the Karaganda Zoo in soviet kazakhstan, can say phrases like 'Batyr is good' and verbs like 'drink' and 'give', a Moscow newspaper reported yesterday. Its said that a recording of its voice was heard recently on the Kazakh state radio. & he just pushes his trunk into his mouth and starts talking' said the deputy director of the zoo, Mr Boris Kosinsky, he told a correspondent from the young communist league newspaper that it all began 3 years ago when a startled night watchman reported that he had heard the elephant talking to itself" — The Daily Telegraph newspaper, 9th April 1980.
# Scientifically-practical actions mentioning the phenomenon
- Scientific conference - Agricultural Institute; Tselinograd, the USSR - Kazakhstan 1983-1989
- The International scientifically-practical conference to an anniversary of the Moscow Zoo; Russia 1984
- The International scientifically-practical conference to an anniversary of the Almaty Zoo; Kazakhstan 1987
- The International scientifically-practical conference; Tallinn — Estonia 1989
- The International zoological conference; Institute of Zoology — Academy of Science Ukraine 1989
- The International scientifically-practical conference to the 125 anniversary of the Leningrad Zoo; Saint Petersburg Russia 1990
# Books
- «The most truthful history or who are talking? An Elephant?!» A.Pogrebnoj-Alexandroff 1979-1993 ISBN 0972126600
- «Reincarnation-Перевоплощение» A.Pogrebnoj-Alexandroff 2001 ISBN 097212666x
- «Speaking animals» A.Dubrov 2001 ISBN 5879690865
- «Speaking birds and speaking animals» O.Silaeva, V.Ilyichev, A.Dubrov 2005 ISBN 5944290161
# Media
- Student documentary film: «Who speaks? The elephant…»; VGIK — Moscow (USSR)
- Audio record of Batyr's voice by the scientist and writer Pogrebnoj-Alexandroff (1979-1983)
# Death reason
- Urological problems: The kidneys stones and an inflammation of kidneys. | Batyr
Template:Otheruses4
Batyr was an Asian Elephant known for his ability to precisely reproduce human speech. Born in 1970, he lived his entire life in the Karaganda Zoo in Karaganda, Kazakhstan. He died in the spring of 1993 having never seen or heard another elephant. Batyr was the offspring of once-wild Indian Elephants (a subspecies of the Asian Elephant). Batyr's mother "Palm" and father "Dubas"[1] had been presented to Kazakhstan's Almaty Zoo by Indian prime minister Jawaharlal Nehru.
Batyr, whose name was a Turkic word meaning The Dashing Equestrian, The Man of Courage or The Athlete, first made his surprising abilities known just before New Year's Day in the winter of 1977. Zoo employees were the first to notice his "speech", but he soon delighted zoo-goers at large by asking his attendants for water and regularly praising (or, infrequently chastising) himself. By 1979, his fame as the "Speaking Elephant" had spread in the wake of various mass-media stories about his abilities. (Many of these contained considerable fabrication and wild conjecture.) Batyr's case was also included in several books on animal behaviour, and in the proceedings of several scientific conferences. These developments drew a spate of zoo visitors, and brought the offer of an exchange—Batyr for a rare Dwarf Chimpanzee—from the Czechoslovak Circus; the offer was rejected by the zoo's employees.
A. N. Pogrebnoj-Aleksandroff, the doctor of sciences[2] who studied Batyr's abilities and wrote many publications about him,[3] said of the elephant:
«Batyr, on the level of natural blares, said the words (including a human slang) by manipulating a trunk. Having put the trunk in a mouth, pressing a tip of the trunk by the bottom of jaw and manipulating of tongue, said words. Besides, being in a corner of the cage (quite often at the nights) with the hanging down and weakened his trunk the elephant said words very silently — that sound is comparable with a sound of ultrasonic devices against mosquitoes or as peep of the mosquitoes, which human hearing well hears to approximately 40-year-old age. During pronouncing of words, only the tip of the trunk of the elephant has been clamped inside and Batyr made insignificant movements by a finger-shaped shoot on the trunk tip».[1]
Various audiovisual recordings were made during Pogrebnoj-Aleksandroff's studies of Batyr;some of these have been transferred to Russia's Moscow State University for further study.
# Lexicon of the elephant Batyr
Batyr said about 20 words in Russian and Kazakh languages, imitated sounds of animals and said short phrases (even said words of human slang)[4]
The full list of words and phrases which Batyr said:
- «Баты́р» — Batyr — abruptly (the trunk in the mouth);
- «Я» — I'm — very abruptly and to combination of his name, at a long pronunciation so «I'm-Batyr», sounded almost together;
- «Ба́ты́р» — Batyr — thoughtfully-tenderly and lingeringly (the trunk in the mouth);
- «Батыр, Батыр, Батыр…» — Batyr, Batyr, Batyr — joyfully running in a cage (the trunk in the mouth);
- «Воды́» — Water — ask (the trunk in the mouth);
- «Хоро́ший» — Good — as is good fellow (the trunk in the mouth);
- «Батыр хоро́ший» — Good Batyr — (the trunk in the mouth);
- «Ой-ё-ёй» — Oh-yo — (it is very sonorous — the trunk in the mouth);
- «Дурак» — The Fool — seldom and abruptly (the trunk in the mouth);
- «Плохой» — Bad — it is rare (the trunk in the mouth);
- «Батыр плохой» — Bad Batyr — it is rare (the trunk in the mouth);
- «Иди́» — Go — (the trunk in the mouth);
- «Иди (на) хуй» — Go onto penis (on-similarity the American expression 'fuck you') — the obscene russian slang; first and unique time during telecast shooting (the trunk in the mouth);
- «Хуй» — The russian slang of the penis — seldom and abruptly (the trunk in the mouth);
- «Ба́-ба» — the short of "babushka" — the grandmother; short children's sound "ba" (the trunk in the mouth);
- «Да́» — Yes — (the trunk in the mouth);
- «Дай» — Give (me) — (the trunk in the mouth);
- «Дай-дай-дай» — Give, give, give... — (the trunk in the mouth);
- «Раз-два-три» — One, two, three — dancing, being turned and hopping (the trunk in the mouth);
- A whistle of human;
- The words of human speech said at level of infrasonic and ultrasonic frequencies;
- A gnash imitation of rubber or polyfoam (foam plastic) on glass;
- The peep of rats or mice;
- The bark of dogs;
- The natural blares of elephants.
# From the press
"SOVIET ZOO HAS TALKING ELEPHANT written by Richard Beeston in Moscow, Batyr, a 10 year old indian elephant at the Karaganda Zoo in soviet kazakhstan, can say phrases like 'Batyr is good' and verbs like 'drink' and 'give', a Moscow newspaper reported yesterday. Its said that a recording of its voice was heard recently on the Kazakh state radio. & he just pushes his trunk into his mouth and starts talking' said the deputy director of the zoo, Mr Boris Kosinsky, he told a correspondent from the young communist league newspaper that it all began 3 years ago when a startled night watchman reported that he had heard the elephant talking to itself" — The Daily Telegraph newspaper, 9th April 1980.
# Scientifically-practical actions mentioning the phenomenon
- Scientific conference - Agricultural Institute; Tselinograd, the USSR - Kazakhstan 1983-1989
- The International scientifically-practical conference to an anniversary of the Moscow Zoo; Russia 1984
- The International scientifically-practical conference to an anniversary of the Almaty Zoo; Kazakhstan 1987
- The International scientifically-practical conference; Tallinn — Estonia 1989
- The International zoological conference; Institute of Zoology — Academy of Science Ukraine 1989
- The International scientifically-practical conference to the 125 anniversary of the Leningrad Zoo; Saint Petersburg Russia 1990
# Books
- «The most truthful history or who are talking? An Elephant?!» A.Pogrebnoj-Alexandroff 1979-1993 ISBN 0972126600
- «Reincarnation-Перевоплощение» A.Pogrebnoj-Alexandroff 2001 ISBN 097212666x
- «Speaking animals» A.Dubrov 2001 ISBN 5879690865
- «Speaking birds and speaking animals» O.Silaeva, V.Ilyichev, A.Dubrov 2005 ISBN 5944290161
# Media
- Student documentary film: «Who speaks? The elephant…»; VGIK — Moscow (USSR)
- Audio record of Batyr's voice by the scientist and writer Pogrebnoj-Alexandroff (1979-1983)
# Death reason
- Urological problems: The kidneys stones and an inflammation of kidneys. | https://www.wikidoc.org/index.php/Batyr | |
2618cb32e077bab7e387659391e87206162dc2c4 | wikidoc | Beedi | Beedi
A beedi (from Hindi बीड़ी, (pronounced: Template:IPA) also known as bidi or biri) is a thin, often flavored, South Asian cigarette made of tobacco wrapped in a tendu (or temburini; Diospyros melonoxylon) leaf, and secured with colored thread at one end. Beedies, though smaller than regular cigarettes produce three times more carbon monoxide and nicotine, and five times more tar than a regular cigarette. Tobacco content in beedies is 10-20%, and, unlike regular cigarettes, beedies do not contain added chemicals. Like all tobacco products, use can cause various cancers.
Beedi-rolling is a cottage industry in India and are typically done by women in their homes. The process of rolling a beedi is similar to that of a handmade cigarette.
Due to the relatively low cost of Beedies (compared to regular cigarettes), they have long been popular among the poor in Bangladesh, Pakistan, Sri Lanka, Cambodia and India. In India, 850 billion are smoked every year.
# Outside South Asia
Beedies, while controversial outside of South Asia, are available in many fruity flavors (such as vanilla, strawberry, chocolate, and mango). Their availability in Indian food markets is usually under the authorities' radar, due to the markets' ethnic clientele and ostensible focus on food, drink, and provisions (and omission of alcohol products). A 1999 survey by San Francisco's Booker T Washington Community Service Center reported that 58% of high school students in San Francisco had tried them, and 31% smoked them at least once a month. Seventy percent of packs purchased contained no warning labels, and about 40% did not contain tax-paid stamps, contributing to their low cost. Many students who have tried a beedi believe it to be less harmful than a regular cigarette due to the ease of inhalation and absence of warning labels. | Beedi
A beedi (from Hindi बीड़ी, (pronounced: Template:IPA) also known as bidi or biri) is a thin, often flavored, South Asian cigarette made of tobacco wrapped in a tendu (or temburini; Diospyros melonoxylon) leaf, and secured with colored thread at one end. Beedies, though smaller than regular cigarettes produce three times more carbon monoxide and nicotine, and five times more tar than a regular cigarette.[1] Tobacco content in beedies is 10-20%, and, unlike regular cigarettes, beedies do not contain added chemicals.[citation needed] Like all tobacco products, use can cause various cancers.
Beedi-rolling is a cottage industry in India and are typically done by women in their homes. The process of rolling a beedi is similar to that of a handmade cigarette.
Due to the relatively low cost of Beedies (compared to regular cigarettes), they have long been popular among the poor in Bangladesh, Pakistan, Sri Lanka, Cambodia and India. In India, 850 billion are smoked every year.
# Outside South Asia
Beedies, while controversial outside of South Asia, are available in many fruity flavors (such as vanilla, strawberry, chocolate, and mango). Their availability in Indian food markets is usually under the authorities' radar, due to the markets' ethnic clientele and ostensible focus on food, drink, and provisions (and omission of alcohol products).[citation needed] A 1999 survey by San Francisco's Booker T Washington Community Service Center reported that 58% of high school students in San Francisco had tried them, and 31% smoked them at least once a month. Seventy percent of packs purchased contained no warning labels, and about 40% did not contain tax-paid stamps, contributing to their low cost.[2] Many students who have tried a beedi believe it to be less harmful than a regular cigarette due to the ease of inhalation and absence of warning labels.[citation needed] | https://www.wikidoc.org/index.php/Beedi | |
8be974697a5421501fea90e76329377ea752d31c | wikidoc | Mania | Mania
# Overview
Mania is a severe medical condition characterized by extremely elevated mood, energy, and unusual thought patterns. There are several possible causes for mania, but it is most often associated with bipolar disorder, where episodes of mania may cyclically alternate with episodes of clinical depression. These cycles may relate to diurnal rhythms and environmental stressors. Mania varies in intensity, from mild mania (known as hypomania) to full-blown mania with psychotic features (hallucinations and delusions).
Manic patients may need to be hospitalized to protect themselves and others. Mania and hypomania have also been associated with creativity and artistic talent..
## Causes
## Drug Causes
Ethambutol
# Symptoms
Symptoms of mania include rapid speech, racing thoughts, decreased need for sleep, hypersexuality, euphoria, grandiosity, and increased interest in goal-directed activities. Mild forms of mania, known as hypomania, cause little or no impairment, but most people who suffer from prolonged hypomania due to bipolar disorder develop full mania.
Another symptom of mania is racing thoughts during which the sufferer is excessively distracted by unimportant stimuli. This negative experience creates an inability to function and an absentmindedness where the person with mania's thoughts totally preoccupy him or her, making him or her unable to keep track of time or be aware of anything besides the neurological pattern of thoughts.
In addition to decreased desire for sleep, other manic symptoms include irritability, anger or rage, delusions, hypersensitivity, hypersexuality, hyper-religiosity, hyperactivity, racing thoughts, talkativeness or rapid speech, and grandiose ideas and plans. In manic and less severe hypomanic cases, the afflicted person may engage in out of character behavior such as questionable business transactions, wasteful expenditures of money, risky sexual activity, abnormal social interaction, or highly vocal arguments uncharacteristic of previous behaviors. These behaviors increase stress in personal relationships, problems at work and increases the risk of altercations with law enforcement as well as being at high risk of impulsively taking part in activities potentially harmful to self and others.
Although "severely elevated mood" sounds somewhat desirable and enjoyable, the experience of mania is often quite unpleasant and sometimes disturbing, if not frightening, for the person involved (and those close to them), and may lead to impulsive behavior that may later be regretted. It can also often be complicated by the sufferer's lack of judgment and insight regarding periods of exacerbation of symptoms. Manic patients are frequently grandiose, obsessive, impulsive, irritable, belligerent, and frequently deny anything is wrong with them. Because mania frequently encourages high energy and decreased perception of need or ability to sleep, within a few days of a manic cycle, sleep-deprived psychosis may appear, further complicating the ability to think clearly. Racing thoughts and misperceptions lead to frustration and decreased ability to communicate with others.
There are different "stages" or "states" of mania. For example, a minor state may involve increased creativity, wit, gregariousness, and ambition. However, a more serious state of mania may involve lack of good judgment, lack of ability to focus, and even psychosis. The victim of mania may feel elated; however, he/she may also feel irritable, frustrated, and may experience derealization.
A mnemonic used to remember the symptoms of mania is DIGFAST:
- D = Distractibility
- I = Indiscretion
- G = Grandiosity
- F = Flight of ideas
- A = Activity increased
- S = Sleep (decreased need for)
- T = Talkativeness (pressured speech)
# Mixed states
Mania can be experienced at the same time as depression, in a mixed episode. Dysphoric mania is primarily manic and agitated depression is primarily depressed. This has caused speculation amongst doctors that mania and depression are two independent axes in a bipolar spectrum, rather than opposites.
There is an increased probability of suicide in the mixed state, as depressed individuals who are also manic have the energy needed to commit suicide.
# Hypomania
Hypomania is a lowered state of mania that does little to impair function or decrease quality of life according to (2007). In hypomania there is less need for sleep, goal motivated behavior and increased metabolism. Though the elevated mood and energy level typical of hypomania could be seen as a benefit, mania generally has many undesirable consequences (2007).
# Associated disorders
A single manic episode is sufficient to diagnose Bipolar I Disorder. Hypomania may be indicative of Bipolar II Disorder or Cyclothymia. However, if prominent psychotic symptoms are present for a duration significantly longer than the mood episode, a diagnosis of Schizoaffective Disorder is more appropriate.
# Medical treatment
Before beginning treatment for mania, careful differential diagnosis must be performed to rule out non-psychiatric causes.
Acute mania in bipolar disorder is typically treated with mood stabilizers and/or antipsychotic medication. Note that these treatments need to be prescribed and monitored carefully to avoid harmful side-effects such as neuroleptic malignant syndrome with the antipsychotic medications. It may be necessary to temporarily admit the patient involuntarily until the patient is stabilized. Antipsychotics and mood stabilizers help stabilize mood of those with mania or depression. They work by blocking the receptor for the neurotransmitter dopamine and allowing serotonin to still work, but in diminished capacity.
When the symptoms of mania have gone, long-term treatment then focuses on prophylactic treatment to try to stabilize the patient's mood, typically through a combination of pharmacotherapy and psychotherapy.
Lithium is the classic mood stabilizer to prevent further manic and depressive episodes. Anticonvulsants such as valproic acid and carbamazepine are also used for prophylaxis. More recent drug solutions include lamotrigine.
# Psychopharmacology
The biological mechanism by which mania occurs is not yet known. One hypothesised cause of mania (among others), is that the amount of the neurotransmitter serotonin in the temporal lobe may be excessively high. This is likely to be only part of the puzzle. Dopamine, norepinephrine, glutamate and gamma-aminobutyric acid also appear to play important roles. The temporal lobe is involved in speech, listening, reading, word association and contains the amygdala, the almond shaped emotional center for the brain. The left amygdala is more active in women who are manic and the orbitofrontal cortex is less active (2005). Emotional stimulation creates the ability for life events to be stored more vividly in the memory. In women, the amygdala becomes similar to one of a manic woman during sex combined with menstruation.
Bipolar disorder is different for men than it is for women. Mania affects the hypothalamus and the pituitary-adrenal-axis by causing it to secrete hormones in different amounts, that accounts for hypersexuality, changes in metabolism, and misdiagnosis as hormonal imbalance. Because the hormone problem stems from a neurological problem hormone therapy isn't the best solution. If serotonin levels are stable, hormones secreted by the pituitary gland will stabilize. Bipolar disorder is similar to a thought disorder combined with hypothyroidism and hyperthyroidism.
In the study done by Brentwood VA Medical Center in Los Angeles, California, antidepressants were taken during mania. One third of bipolar patients developed antidepressant induced mania from their healthy state and one fourth developed antidepressant induced rapid cycling from their healthy state. For those with type II bipolar disorder, antidepressants decrease the gaps between the depression and mania (1995).
# Mania and over the counter prescription drugs
Phenylpropanolamine (PPA) is a sympathomimetic drug similar in structure to amphetamine which was formerly present in over 130 medications, primarily decongestants, cough/cold remedies, and anorectic agents.
A report on PPA, from the Dept. of Psychiatry, F. Edward Hebert School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, Maryland. Pharmacopsychiatry 1988 stated:
PPA is no longer available in any medication in the United States as of the year 2000.
# Personal Accounts
In "Electroboy: a Memoir of Mania" by Andy Behrman, he describes his experience of mania as "the most perfect prescription glasses with which to see the world...life appears in front of you like an oversized movie screen" (2002). Behrman indicates early in his memoir that he sees himself not as a person suffering from an uncontrollable disabling illness, but as a director of the movie that is his vivid and emotionally alive life. "When I'm manic, I'm so awake and alert, that my eyelashes fluttering on the pillow sound like thunder" (2002).
Caveat: See "Symptoms" above. | Mania
Template:DiseaseDisorder infobox
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
# Overview
Mania is a severe medical condition characterized by extremely elevated mood, energy, and unusual thought patterns. There are several possible causes for mania, but it is most often associated with bipolar disorder, where episodes of mania may cyclically alternate with episodes of clinical depression. These cycles may relate to diurnal rhythms and environmental stressors. Mania varies in intensity, from mild mania (known as hypomania) to full-blown mania with psychotic features (hallucinations and delusions).
Manic patients may need to be hospitalized to protect themselves and others. Mania and hypomania have also been associated with creativity and artistic talent.[1].
## Causes
## Drug Causes
Ethambutol
# Symptoms
Symptoms of mania include rapid speech, racing thoughts, decreased need for sleep, hypersexuality, euphoria, grandiosity, and increased interest in goal-directed activities. [2] Mild forms of mania, known as hypomania, cause little or no impairment, but most people who suffer from prolonged hypomania due to bipolar disorder develop full mania.
Another symptom of mania is racing thoughts during which the sufferer is excessively distracted by unimportant stimuli. [3] This negative experience creates an inability to function and an absentmindedness where the person with mania's thoughts totally preoccupy him or her, making him or her unable to keep track of time or be aware of anything besides the neurological pattern of thoughts.
In addition to decreased desire for sleep, other manic symptoms include irritability, anger or rage, delusions, hypersensitivity, hypersexuality, hyper-religiosity, hyperactivity, racing thoughts, talkativeness or rapid speech, and grandiose ideas and plans. In manic and less severe hypomanic cases, the afflicted person may engage in out of character behavior such as questionable business transactions, wasteful expenditures of money, risky sexual activity, abnormal social interaction, or highly vocal arguments uncharacteristic of previous behaviors. These behaviors increase stress in personal relationships, problems at work and increases the risk of altercations with law enforcement as well as being at high risk of impulsively taking part in activities potentially harmful to self and others.
Although "severely elevated mood" sounds somewhat desirable and enjoyable, the experience of mania is often quite unpleasant and sometimes disturbing, if not frightening, for the person involved (and those close to them), and may lead to impulsive behavior that may later be regretted. It can also often be complicated by the sufferer's lack of judgment and insight regarding periods of exacerbation of symptoms. Manic patients are frequently grandiose, obsessive, impulsive, irritable, belligerent, and frequently deny anything is wrong with them. Because mania frequently encourages high energy and decreased perception of need or ability to sleep, within a few days of a manic cycle, sleep-deprived psychosis may appear, further complicating the ability to think clearly. Racing thoughts and misperceptions lead to frustration and decreased ability to communicate with others.
There are different "stages" or "states" of mania. For example, a minor state may involve increased creativity, wit, gregariousness, and ambition. However, a more serious state of mania may involve lack of good judgment, lack of ability to focus, and even psychosis. The victim of mania may feel elated; however, he/she may also feel irritable, frustrated, and may experience derealization.
A mnemonic used to remember the symptoms of mania is DIGFAST: [4]
- D = Distractibility
- I = Indiscretion
- G = Grandiosity
- F = Flight of ideas
- A = Activity increased
- S = Sleep (decreased need for)
- T = Talkativeness (pressured speech)
# Mixed states
Mania can be experienced at the same time as depression, in a mixed episode. Dysphoric mania is primarily manic and agitated depression is primarily depressed. This has caused speculation amongst doctors that mania and depression are two independent axes in a bipolar spectrum, rather than opposites.
There is an increased probability of suicide in the mixed state, as depressed individuals who are also manic have the energy needed to commit suicide.
# Hypomania
Hypomania is a lowered state of mania that does little to impair function or decrease quality of life according to (2007). In hypomania there is less need for sleep, goal motivated behavior and increased metabolism. Though the elevated mood and energy level typical of hypomania could be seen as a benefit, mania generally has many undesirable consequences (2007).
# Associated disorders
A single manic episode is sufficient to diagnose Bipolar I Disorder. Hypomania may be indicative of Bipolar II Disorder or Cyclothymia. However, if prominent psychotic symptoms are present for a duration significantly longer than the mood episode, a diagnosis of Schizoaffective Disorder is more appropriate.
# Medical treatment
Before beginning treatment for mania, careful differential diagnosis must be performed to rule out non-psychiatric causes.
Acute mania in bipolar disorder is typically treated with mood stabilizers and/or antipsychotic medication. Note that these treatments need to be prescribed and monitored carefully to avoid harmful side-effects such as neuroleptic malignant syndrome with the antipsychotic medications. It may be necessary to temporarily admit the patient involuntarily until the patient is stabilized. Antipsychotics and mood stabilizers help stabilize mood of those with mania or depression. They work by blocking the receptor for the neurotransmitter dopamine and allowing serotonin to still work, but in diminished capacity.
When the symptoms of mania have gone, long-term treatment then focuses on prophylactic treatment to try to stabilize the patient's mood, typically through a combination of pharmacotherapy and psychotherapy.
Lithium is the classic mood stabilizer to prevent further manic and depressive episodes. Anticonvulsants such as valproic acid and carbamazepine are also used for prophylaxis. More recent drug solutions include lamotrigine.
# Psychopharmacology
The biological mechanism by which mania occurs is not yet known. One hypothesised cause of mania (among others), is that the amount of the neurotransmitter serotonin in the temporal lobe may be excessively high. This is likely to be only part of the puzzle. Dopamine, norepinephrine, glutamate and gamma-aminobutyric acid also appear to play important roles. The temporal lobe is involved in speech, listening, reading, word association and contains the amygdala, the almond shaped emotional center for the brain. The left amygdala is more active in women who are manic and the orbitofrontal cortex is less active (2005). Emotional stimulation creates the ability for life events to be stored more vividly in the memory. In women, the amygdala becomes similar to one of a manic woman during sex combined with menstruation.
Bipolar disorder is different for men than it is for women. Mania affects the hypothalamus and the pituitary-adrenal-axis by causing it to secrete hormones in different amounts, that accounts for hypersexuality, changes in metabolism, and misdiagnosis as hormonal imbalance. Because the hormone problem stems from a neurological problem hormone therapy isn't the best solution. If serotonin levels are stable, hormones secreted by the pituitary gland will stabilize. Bipolar disorder is similar to a thought disorder combined with hypothyroidism and hyperthyroidism.
In the study done by Brentwood VA Medical Center in Los Angeles, California, antidepressants were taken during mania. One third of bipolar patients developed antidepressant induced mania from their healthy state and one fourth developed antidepressant induced rapid cycling from their healthy state. For those with type II bipolar disorder, antidepressants decrease the gaps between the depression and mania (1995).
# Mania and over the counter prescription drugs
Phenylpropanolamine (PPA) is a sympathomimetic drug similar in structure to amphetamine which was formerly present in over 130 medications, primarily decongestants, cough/cold remedies, and anorectic agents.
A report on PPA, from the Dept. of Psychiatry, F. Edward Hebert School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, Maryland. Pharmacopsychiatry 1988 stated:
PPA is no longer available in any medication in the United States as of the year 2000.
# Personal Accounts
In "Electroboy: a Memoir of Mania" by Andy Behrman, he describes his experience of mania as "the most perfect prescription glasses with which to see the world...life appears in front of you like an oversized movie screen" (2002). Behrman indicates early in his memoir that he sees himself not as a person suffering from an uncontrollable disabling illness, but as a director of the movie that is his vivid and emotionally alive life. "When I'm manic, I'm so awake and alert, that my eyelashes fluttering on the pillow sound like thunder" (2002).
Caveat: See "Symptoms" above. | https://www.wikidoc.org/index.php/Bell_mania | |
ffb1bb93a8fc37a27ec910d4b19dc50d4136ba5f | wikidoc | Tumor | Tumor
# Overview
A Tumor or tumour (via Old French tumour from Latin tumor "swelling") originally meant an abnormal swelling of the flesh. In contemporary English, tumor has evolved to become synonymous with neoplasia , all other forms being called swelling . This tendency has also become common in medical literature. The noun tumefaction, derived from the adjective tumefied, is the current medical term for non-neoplastic tumors .
# Causes
Tumors and/or swellings can be caused by:
- Neoplasia, an abnormal proliferation of tissues. Most (not all) neoplasms cause a tumor. Neoplasms (or tumors) may be benign or malignant (cancer).
- Non-neoplastic causes :
Inflammation, by far the most common cause; tumor is one of the classic signs of inflammation. The lump following a blow on the head is a typical example. Infection is another common cause of inflammation.
Edema, the accumulation of an excessive amount of fluid in the tissues, either with or without inflammation.
Malformation, a congenital anomaly in the architecture of a tissue. A typical example is an epidermal nevus.
Cyst, the accumulation of fluid in a closed structure. Breast cysts are a typical example.
Hemorrhage in a closed structure.
- Inflammation, by far the most common cause; tumor is one of the classic signs of inflammation. The lump following a blow on the head is a typical example. Infection is another common cause of inflammation.
- Edema, the accumulation of an excessive amount of fluid in the tissues, either with or without inflammation.
- Malformation, a congenital anomaly in the architecture of a tissue. A typical example is an epidermal nevus.
- Cyst, the accumulation of fluid in a closed structure. Breast cysts are a typical example.
- Hemorrhage in a closed structure.
Other forms of swelling are part of the normal functions of the body and may or may not be included as causes of tumor. Examples include enlargement of the uterus in pregnancy and erection of the penis.
This article is intentionally kept short. For a detailed discussion, see Cancer. | Tumor
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
# Overview
A Tumor or tumour (via Old French tumour from Latin tumor "swelling")[1] originally meant an abnormal swelling of the flesh. In contemporary English, tumor has evolved to become synonymous with neoplasia [2], all other forms being called swelling [3]. This tendency has also become common in medical literature. The noun tumefaction, derived from the adjective tumefied, is the current medical term for non-neoplastic tumors [4].
# Causes
Tumors and/or swellings can be caused by:
- Neoplasia, an abnormal proliferation of tissues. Most (not all) neoplasms cause a tumor. Neoplasms (or tumors) may be benign or malignant (cancer).
- Non-neoplastic causes :
Inflammation, by far the most common cause; tumor is one of the classic signs of inflammation.[5] The lump following a blow on the head is a typical example. Infection is another common cause of inflammation.
Edema, the accumulation of an excessive amount of fluid in the tissues, either with or without inflammation.
Malformation, a congenital anomaly in the architecture of a tissue. A typical example is an epidermal nevus.
Cyst, the accumulation of fluid in a closed structure. Breast cysts are a typical example.
Hemorrhage in a closed structure.
- Inflammation, by far the most common cause; tumor is one of the classic signs of inflammation.[5] The lump following a blow on the head is a typical example. Infection is another common cause of inflammation.
- Edema, the accumulation of an excessive amount of fluid in the tissues, either with or without inflammation.
- Malformation, a congenital anomaly in the architecture of a tissue. A typical example is an epidermal nevus.
- Cyst, the accumulation of fluid in a closed structure. Breast cysts are a typical example.
- Hemorrhage in a closed structure.
Other forms of swelling are part of the normal functions of the body and may or may not be included as causes of tumor. Examples include enlargement of the uterus in pregnancy and erection of the penis.
This article is intentionally kept short. For a detailed discussion, see Cancer. | https://www.wikidoc.org/index.php/Benign_tumors | |
c53977337626fd68c007039dfb49f9e7a3bddf1e | wikidoc | Grief | Grief
# Overview
Grief is a multi-faceted response to loss. Although conventionally focused on the emotional response to loss, it also has physical, cognitive, behavioral, social and philosophical dimensions. Common to human experience is the death of a loved one, whether it be a friend, family, or other close companion. While the terms are often used interchangeably, bereavement often refers to the state of loss, and grief to the reaction to loss. Losses can range from loss of employment, pets, status, a sense of safety, order or possessions to the loss of the people nearest to us. Our response to loss is varied and researchers have moved away from conventional views of grief (that is, that people move through an orderly and predictable series of responses to loss) to one that considers the wide variety of responses that are influenced by personality, family, culture, and spiritual and religious beliefs and practices.
Bereavement, while a normal part of life for us all, carries a degree of risk when limited support is available. Severe reactions to loss may carry over into familial relations and cause trauma for children, spouses and any other family members: there is an increased risk of marital breakup following the death of a child, for example. Many forms of what we term 'mental illness' have loss as their root, but are covered by many years and circumstances this often goes unnoticed. Issues of personal faith and beliefs may also face challenge, as bereaved persons reassess personal definitions in the face of great pain. While many who grieve are able to work through their loss independently, accessing additional support from bereavement professionals may promote the process of healing. Grief counseling, professional support groups or educational classes, and peer-led support groups are primary resources available to the bereaved. In the United States, local hospice agencies may be an important first contact for those seeking bereavement support.
# Stage theories and processes
Some researchers such as Dr. Elisabeth Kübler-Ross and others have posited sequential stages including denial, anger, bargaining, depression and acceptance, which are commonly referred to as the "grief cycle". As research progressed over the past 40 years, many who worked with the bereaved found stage models too simplistic and instead began to look at processes, dynamics, and experiences common to all. John Bowlby, a noted psychiatrist, outlined the ebb and flow of processes such as Shock and Numbness, Yearning and Searching, Disorganization and Despair, and Reorganization. Bowlby and Parkes both note psychophysiologic components of grief as well. Included in these processes are:
## Shock and denial
Feelings of unreality, depersonalization, withdrawal, and an anesthetizing of affect.
Unable to come to terms with what just occurred.
## Volatile Reactions
"Whenever one's identity and social order face the possibility of destruction, there is a natural tendency to feel angry, frustrated, helpless, and/or hurt. The volatile reactions of terror, hatred, resentment, and jealousy are often experienced as emotional manifestations of these feelings." (see the article entitled The Grieving Process by Michael R. Leming and George E. Dickinson)
## Disorganization and despair
These are the processes we normally associate with bereavement, the mourning and severe pain of being away from the loved person or situation.
## Reorganization
Reorganization is the assimilation of the loss of something or someone and redefining of life and meaning without the deceased.
# Risks
Many studies have looked at the bereaved in terms of increased risks for stress-related illnesses. Colin Murray Parkes in the 1960s and 1970s in England noted increased doctor visits, with symptoms such as abdominal pain, breathing difficulties, and so forth in the first six months following a death. Others have noted increased mortality rates (Ward, A.W. 1976) and Bunch et al
found a five times greater risk of suicide in teens following the death of a parent. Grief puts a great stress on the physical body as well as on the psyche, resulting in wear and tear beyond what is normal.
# Normal and complicated grief
Complicated grief can be differentiated from normal grief, in that, normal grief typically involves at least two of Elisabeth Kubler-Ross' 5 grief stages, though not necessarily in any order. Complicated grief typically cycles through these 5 stages and then some, processing them out of order and often much more rapidly. Some people commit suicide to end the pain and suffering of grief. Examples of complicated grief can often be found in those who have survived a suicide attempt (Hsu, 2002). While the experience of grief is a very individual process depending on many factors, certain commonalities are often reported. Nightmares, appetite problems, dryness of mouth, shortness of breath, sleep disorders and repetitive motions to avoid pain are often reported, and are perfectly normal. Even hallucinatory experiences may be normal early in grief, and usual definitions will not suffice, necessitating a lot of grace for the bereaved. Complicated grief responses almost always are a function of intensity and timing: a grief that after a year or two begins to worsen, accompanied by unusual behaviors, is a warning sign, but even here, caution must be used; it takes time to say goodbye.
Complicated grief is usually grief where the story of the loss is in some ways difficult to tell. Deaths such as suicides, murders, car crashes, and almost any other sudden and unexpected death can result in complicated grief simply because they leave people in such shock that they have great difficulty in integrating what happened into their reality. A simple way to describe this is that there is something that keeps the person from being able to integrate the "story" of the loss and therefore it leaves the person struggling with an initial task of simply believing that the loss has occurred. Variables surrounding the death such as expectedness, naturalness, presence of violence, ambivalence, degree of attachment, and others play into the presence of complicated grief. All too often complicated grief can last for years and most people (friends of the mourner) will recoil when hearing that this sort of grief may still be present after several years. This needs to be differentiated from the clinical problem of becoming "identified" with the grief where people are reluctant to release the grief due to the grief having become a static part of who the person sees themselves as being. It takes a good therapist to be able to tell the difference. It is sometimes very difficult for a layperson to tell the difference. Use caution. It is worth mentioning that many have found that EMDR can be very helpful with complicated grief particularly when the therapist is knowledgable about grief and trauma.
# Types of bereavement
Differing bereavements along the life cycle may have different manifestations and problems which are age related, mostly because of cognitive and emotional skills along the way. Children will exhibit their mourning very differently in reaction to the loss of a parent than a widow would to the loss of a spouse. Reactions in one type of bereavement may be perfectly normal, but in another the same reaction could be problematic. The kind of loss must be taken under consideration when determining how to help.
## Childhood bereavement
When a parent dies, children may have symptoms of psychopathology, but they are less severe than in children with major depression (Cerel, 2006). The loss of a parent, grandparent or sibling can be very troubling in childhood, but even in childhood there are age differences in relation to the loss. A very young child, under one or two, may be felt to have no reaction if a carer dies, but this is far from the truth. At a time when trust and dependency are formed, a break even of no more than separation can cause problems in wellbeing; this is especially true if the loss is around critical periods such as 8-12 months when attachment and separation are at their height in formation and even a brief separation from a parent can cause distress. (Ainsworth 1963) A change in carers can have lifelong consequences, which may become so blurred as to be untraceable. As a child grows older, death is still difficult to assimilate and that fact affects the way a child responds. For example, younger children will find the 'fact' of death a changeable thing: one child believed her deceased mother could be restored with 'band-aids', and children often see death as curable or reversible, more as a separation. Reactions here may manifest themselves in 'acting out' behaviors: a return to earlier behaviors such as sucking thumbs, clinging to a toy or angry behavior: they do not have the maturity to mourn as an adult, but the intensity is there. As children enter pre-teen and teen years, there is a more mature understanding. Adolescents may respond by delinquency, or oppositely become 'over-achievers': repetitive actions are not uncommon such as washing a car repeatedly or taking up repetitive tasks such as sewing, computer games etc. It is an effort to stay 'above' the grief. Childhood loss as mentioned before can predispose a child not only to physical illness but to emotional problems and an increased risk for suicide, especially in the adolescent period.
## Death of a child
Death of a child can take the form of a loss in infancy such as miscarriage, stillbirth or neonatal death, SIDS, or the death of an older child. In all cases, parents find the grief almost unbearably devastating and while
persons may rate the death of a spouse as first in traumatic life events, the death of a child is still perhaps one of the most intense forms of grief, and holds greater risk factors. This loss also bears a lifelong process: one does not easily get 'over' the loss but instead must assimilate and live with the death. Intervention and comforting support can make all the difference to the survival of a parent in this type of grief but the risk factors are great and may include family breakup or suicide. In the event of a miscarriage or abortion it is important for friends and family members to acknowledge the loss of the pregnancy, and not to attempt to minimalize the significance of a pregnancy that did not come to term. Feelings of guilt, almost always unfounded, are pervasive, and the dependent nature of the relationship disposes parents to a variety of problems as they seek to cope with this great loss. Parents that suffer miscarriage or abortion may experience resentment towards others who experience successful pregnancies.
## Death of a spouse
Although the death of a spouse may be an expected change, particularly as we age, it is a particularly powerful loss of a loved-one. A spouse, though, often becomes part of the other in a unique way: many widows and widowers describe losing 'half' of themselves, and after a long marriage, at older ages, the elderly may find it a very difficult assimilation to begin anew. Further, most couples have a division of 'tasks' or 'labor', e.g. the husband mows the yard, the wife pays the bills, etc. which in addition to dealing with great grief and life changes means added responsibilities for the bereaved. Social isolation may also become eminent as many groups composed of couples find it difficult adjust to the new identity of the bereaved. When queried about what in life is most troubling, most rate death of a spouse first, although the death of a child presents more risk factors.
## Death of a parent
Responses and reactions of older children or adults to the death of a parent. There is also an increase in awareness of one's own health and mortality.
## Death of a sibling
Responses and reactions of older children or adults to the death of a sibling.
There is a saying (Compassionate Friends} that if you have lost your parents, you have lost your past; if you lost your children, you have lost your future; if you have lost your spouse, you have lost your present; and if you have lost your sibling, then you have lost a part of your past, present and future.
## Loss of children through divorce or kidnapping
Responses of parents accepting permanent loss of children through the reality of the divorce system, or through kidnapping. This loss differs from the death of a child in that the grief process is prolonged or denied because of hope that the relationship will be restored. This is often not the case.
## Other losses
Many other losses predispose persons to these same experiences, although often not as severely.
Loss reactions may occur after the loss of a romantic relationship (i.e. divorce or break up), a vocation, a pet (animal loss), a home, children leaving home (empty nest), a friend, a favored appointment or desire, etc. While the reaction may not be as intense, experiences of loss may still show in these forms of bereavement. | Grief
For patient information click here
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
# Overview
Grief is a multi-faceted response to loss. Although conventionally focused on the emotional response to loss, it also has physical, cognitive, behavioral, social and philosophical dimensions. Common to human experience is the death of a loved one, whether it be a friend, family, or other close companion. While the terms are often used interchangeably, bereavement often refers to the state of loss, and grief to the reaction to loss. Losses can range from loss of employment, pets, status, a sense of safety, order or possessions to the loss of the people nearest to us. Our response to loss is varied and researchers have moved away from conventional views of grief (that is, that people move through an orderly and predictable series of responses to loss) to one that considers the wide variety of responses that are influenced by personality, family, culture, and spiritual and religious beliefs and practices.
Bereavement, while a normal part of life for us all, carries a degree of risk when limited support is available. Severe reactions to loss may carry over into familial relations and cause trauma for children, spouses and any other family members: there is an increased risk of marital breakup following the death of a child, for example. Many forms of what we term 'mental illness' have loss as their root, but are covered by many years and circumstances this often goes unnoticed. Issues of personal faith and beliefs may also face challenge, as bereaved persons reassess personal definitions in the face of great pain. While many who grieve are able to work through their loss independently, accessing additional support from bereavement professionals may promote the process of healing. Grief counseling, professional support groups or educational classes, and peer-led support groups are primary resources available to the bereaved. In the United States, local hospice agencies may be an important first contact for those seeking bereavement support.
# Stage theories and processes
Some researchers such as Dr. Elisabeth Kübler-Ross and others have posited sequential stages including denial, anger, bargaining, depression and acceptance, which are commonly referred to as the "grief cycle". As research progressed over the past 40 years, many who worked with the bereaved found stage models too simplistic and instead began to look at processes, dynamics, and experiences common to all. John Bowlby, a noted psychiatrist, outlined the ebb and flow of processes such as Shock and Numbness, Yearning and Searching, Disorganization and Despair, and Reorganization. Bowlby and Parkes both note psychophysiologic components of grief as well. Included in these processes are:
## Shock and denial
Feelings of unreality, depersonalization, withdrawal, and an anesthetizing of affect.
Unable to come to terms with what just occurred.
## Volatile Reactions
"Whenever one's identity and social order face the possibility of destruction, there is a natural tendency to feel angry, frustrated, helpless, and/or hurt. The volatile reactions of terror, hatred, resentment, and jealousy are often experienced as emotional manifestations of these feelings." (see the article entitled The Grieving Process by Michael R. Leming and George E. Dickinson)
## Disorganization and despair
These are the processes we normally associate with bereavement, the mourning and severe pain of being away from the loved person or situation.
## Reorganization
Reorganization is the assimilation of the loss of something or someone and redefining of life and meaning without the deceased.
# Risks
Many studies have looked at the bereaved in terms of increased risks for stress-related illnesses. Colin Murray Parkes in the 1960s and 1970s in England noted increased doctor visits, with symptoms such as abdominal pain, breathing difficulties, and so forth in the first six months following a death. Others have noted increased mortality rates (Ward, A.W. 1976) and Bunch et al
found a five times greater risk of suicide in teens following the death of a parent. Grief puts a great stress on the physical body as well as on the psyche, resulting in wear and tear beyond what is normal.
# Normal and complicated grief
Complicated grief can be differentiated from normal grief, in that, normal grief typically involves at least two of Elisabeth Kubler-Ross' 5 grief stages, though not necessarily in any order. Complicated grief typically cycles through these 5 stages and then some, processing them out of order and often much more rapidly. Some people commit suicide to end the pain and suffering of grief. Examples of complicated grief can often be found in those who have survived a suicide attempt (Hsu, 2002). While the experience of grief is a very individual process depending on many factors, certain commonalities are often reported. Nightmares, appetite problems, dryness of mouth, shortness of breath, sleep disorders and repetitive motions to avoid pain are often reported, and are perfectly normal. Even hallucinatory experiences may be normal early in grief, and usual definitions will not suffice, necessitating a lot of grace for the bereaved. Complicated grief responses almost always are a function of intensity and timing: a grief that after a year or two begins to worsen, accompanied by unusual behaviors, is a warning sign, but even here, caution must be used; it takes time to say goodbye.
Complicated grief is usually grief where the story of the loss is in some ways difficult to tell. Deaths such as suicides, murders, car crashes, and almost any other sudden and unexpected death can result in complicated grief simply because they leave people in such shock that they have great difficulty in integrating what happened into their reality. A simple way to describe this is that there is something that keeps the person from being able to integrate the "story" of the loss and therefore it leaves the person struggling with an initial task of simply believing that the loss has occurred. Variables surrounding the death such as expectedness, naturalness, presence of violence, ambivalence, degree of attachment, and others play into the presence of complicated grief. All too often complicated grief can last for years and most people (friends of the mourner) will recoil when hearing that this sort of grief may still be present after several years. This needs to be differentiated from the clinical problem of becoming "identified" with the grief where people are reluctant to release the grief due to the grief having become a static part of who the person sees themselves as being. It takes a good therapist to be able to tell the difference. It is sometimes very difficult for a layperson to tell the difference. Use caution. It is worth mentioning that many have found that EMDR can be very helpful with complicated grief particularly when the therapist is knowledgable about grief and trauma.
# Types of bereavement
Differing bereavements along the life cycle may have different manifestations and problems which are age related, mostly because of cognitive and emotional skills along the way. Children will exhibit their mourning very differently in reaction to the loss of a parent than a widow would to the loss of a spouse. Reactions in one type of bereavement may be perfectly normal, but in another the same reaction could be problematic. The kind of loss must be taken under consideration when determining how to help.
## Childhood bereavement
When a parent dies, children may have symptoms of psychopathology, but they are less severe than in children with major depression (Cerel, 2006). The loss of a parent, grandparent or sibling can be very troubling in childhood, but even in childhood there are age differences in relation to the loss. A very young child, under one or two, may be felt to have no reaction if a carer dies, but this is far from the truth. At a time when trust and dependency are formed, a break even of no more than separation can cause problems in wellbeing; this is especially true if the loss is around critical periods such as 8-12 months when attachment and separation are at their height in formation and even a brief separation from a parent can cause distress. (Ainsworth 1963) A change in carers can have lifelong consequences, which may become so blurred as to be untraceable. As a child grows older, death is still difficult to assimilate and that fact affects the way a child responds. For example, younger children will find the 'fact' of death a changeable thing: one child believed her deceased mother could be restored with 'band-aids', and children often see death as curable or reversible, more as a separation. Reactions here may manifest themselves in 'acting out' behaviors: a return to earlier behaviors such as sucking thumbs, clinging to a toy or angry behavior: they do not have the maturity to mourn as an adult, but the intensity is there. As children enter pre-teen and teen years, there is a more mature understanding. Adolescents may respond by delinquency, or oppositely become 'over-achievers': repetitive actions are not uncommon such as washing a car repeatedly or taking up repetitive tasks such as sewing, computer games etc. It is an effort to stay 'above' the grief. Childhood loss as mentioned before can predispose a child not only to physical illness but to emotional problems and an increased risk for suicide, especially in the adolescent period.
## Death of a child
Death of a child can take the form of a loss in infancy such as miscarriage, stillbirth or neonatal death, SIDS, or the death of an older child. In all cases, parents find the grief almost unbearably devastating and while
persons may rate the death of a spouse as first in traumatic life events, the death of a child is still perhaps one of the most intense forms of grief, and holds greater risk factors. This loss also bears a lifelong process: one does not easily get 'over' the loss but instead must assimilate and live with the death. Intervention and comforting support can make all the difference to the survival of a parent in this type of grief but the risk factors are great and may include family breakup or suicide. In the event of a miscarriage or abortion it is important for friends and family members to acknowledge the loss of the pregnancy, and not to attempt to minimalize the significance of a pregnancy that did not come to term. Feelings of guilt, almost always unfounded, are pervasive, and the dependent nature of the relationship disposes parents to a variety of problems as they seek to cope with this great loss. Parents that suffer miscarriage or abortion may experience resentment towards others who experience successful pregnancies.
## Death of a spouse
Although the death of a spouse may be an expected change, particularly as we age, it is a particularly powerful loss of a loved-one. A spouse, though, often becomes part of the other in a unique way: many widows and widowers describe losing 'half' of themselves, and after a long marriage, at older ages, the elderly may find it a very difficult assimilation to begin anew. Further, most couples have a division of 'tasks' or 'labor', e.g. the husband mows the yard, the wife pays the bills, etc. which in addition to dealing with great grief and life changes means added responsibilities for the bereaved. Social isolation may also become eminent as many groups composed of couples find it difficult adjust to the new identity of the bereaved. When queried about what in life is most troubling, most rate death of a spouse first, although the death of a child presents more risk factors.
## Death of a parent
Responses and reactions of older children or adults to the death of a parent. There is also an increase in awareness of one's own health and mortality.
## Death of a sibling
Responses and reactions of older children or adults to the death of a sibling.
There is a saying (Compassionate Friends} that if you have lost your parents, you have lost your past; if you lost your children, you have lost your future; if you have lost your spouse, you have lost your present; and if you have lost your sibling, then you have lost a part of your past, present and future.
## Loss of children through divorce or kidnapping
Responses of parents accepting permanent loss of children through the reality of the divorce system, or through kidnapping. This loss differs from the death of a child in that the grief process is prolonged or denied because of hope that the relationship will be restored. This is often not the case.
## Other losses
Many other losses predispose persons to these same experiences, although often not as severely.
Loss reactions may occur after the loss of a romantic relationship (i.e. divorce or break up), a vocation, a pet (animal loss), a home, children leaving home (empty nest), a friend, a favored appointment or desire, etc. While the reaction may not be as intense, experiences of loss may still show in these forms of bereavement. | https://www.wikidoc.org/index.php/Bereavement | |
51a8232047ff72aa6601a8f1ab264923b3429466 | wikidoc | Betel | Betel
The Betel (Piper betle) is a spice whose leaves have medicinal properties. The plant is evergreen and perennial, with glossy heart-shaped leaves and white catkins, and grows to a height of about 1 metre. The Betel plant originated in Malaysia and now grows in India, Indonesia and Sri Lanka. The best Betel leaf is the "Magahi" variety (literally from the Magadha region) grown near Patna in Bihar, India. The plant is known by a series of different names in the regions in which it is consumed - among these are Vetrilai (Tamil), Vettila (Malayalam).
# Ingredients
The active ingredients of betel oil, which is obtained from the leaves, are primarily a class of allylbenzene compounds. Though particular emphasis has been placed on chavibetol (betel-phenol; 3-hydroxy-4-methoxyallylbenzene), it also contains chavicol (p-allyl-phenol; 4-allyl-phenol), estragole (p-allyl-anisole; 4-methoxy-allylbenzene), eugenol (allylguaiacol; 4-hydroxy-3-methoxy-allylbenzene; 2-methoxy-4-allyl-phenol), methyl eugenol (eugenol methyl ether; 3,4-dimethoxy-allylbenzene), and hydroxycatechol (2,4-dihydroxy-allylbenzene).
Several terpenes and terpenoids are present in the betel oil as well. There are two monoterpenes, p-cymene and terpinene, and two monoterpenoids, eucalyptol and carvacrol. Additionally, there are two sesquiterpenes, cadinene and caryophyllene.
# Chewing
In India and parts of Southeast Asia, the leaves are chewed together with the mineral slaked lime (calcium hydroxide) and the areca nut which, by association, is sometimes inaccurately called the "betel nut". The lime acts to keep the active ingredient in its freebase or alkaline form, thus enabling it to enter the bloodstream via sublingual absorption. The areca nut contains the alkaloid arecoline, which promotes salivation (the saliva is stained red), and is itself a stimulant. This combination, known as a "betel quid", has been used for several thousand years. Tobacco is sometimes added.
Betel leaves are used as a stimulant, an antiseptic and a breath-freshener Paan. In Ayurvedic medicine, they are used as an aphrodisiac. In Malaysia they are used to treat headaches, arthritis and joint pain. In Thailand, Indonesia and China they are used to relieve toothache. In Indonesia they are drunk as an infusion and used as an antibiotic. They are also used in an infusion to cure indigestion, as a topical cure for constipation, as a decongestant and as an aid to lactation.
In India, betel is used to cast out (cure) worms.
In India, the betel and areca play an important role in Indian culture especially among Hindus. All the traditional ceremonies governing the lives of Hindus use betel and areca. For example to pay money to the priest, they keep money in the betel leaves and place it beside the priest.
The betel and areca also play an important role in Vietnamese culture. In Vietnamese there is a saying that "the betel begins the conversation", referring to the practice of people chewing betel in formal occasions or "to break the ice" in awkward situational conversations. The betel leaves and areca nuts are used ceremonially in traditional Vietnamese weddings. Based on a folk tale about the origins of these plants, the groom traditionally offer the bride's parents betel leaves and areca nuts (among other things) in exchange for the bride. The betel and areca are such important symbols of love and marriage such that in Vietnamese the phrase "matters of betel and areca" (chuyện trầu cau) is synonymous with marriage.
A related plant P. sarmentosum, which is used in cooking, is sometimes called "wild betel leaf".
WARNING: Chewing Betel has been associated with oral and esophageal squamous cell carcinoma.
# Further reading
- P. Guha: Betel leaf:The neglected green gold of India. J. Hum Ecol., 19(2) 2006
- U J Nair et al: Role of lime in the generation of reactive oxygen species from betel-quid ingredients. | Betel
The Betel (Piper betle) is a spice whose leaves have medicinal properties. The plant is evergreen and perennial, with glossy heart-shaped leaves and white catkins, and grows to a height of about 1 metre. The Betel plant originated in Malaysia and now grows in India, Indonesia and Sri Lanka. The best Betel leaf is the "Magahi" variety (literally from the Magadha region) grown near Patna in Bihar, India. The plant is known by a series of different names in the regions in which it is consumed - among these are Vetrilai (Tamil), Vettila (Malayalam).
# Ingredients
The active ingredients of betel oil, which is obtained from the leaves, are primarily a class of allylbenzene compounds. Though particular emphasis has been placed on chavibetol (betel-phenol; 3-hydroxy-4-methoxyallylbenzene), it also contains chavicol (p-allyl-phenol; 4-allyl-phenol), estragole (p-allyl-anisole; 4-methoxy-allylbenzene), eugenol (allylguaiacol; 4-hydroxy-3-methoxy-allylbenzene; 2-methoxy-4-allyl-phenol), methyl eugenol (eugenol methyl ether; 3,4-dimethoxy-allylbenzene), and hydroxycatechol (2,4-dihydroxy-allylbenzene).
Several terpenes and terpenoids are present in the betel oil as well. There are two monoterpenes, p-cymene and terpinene, and two monoterpenoids, eucalyptol and carvacrol. Additionally, there are two sesquiterpenes, cadinene and caryophyllene.
# Chewing
In India and parts of Southeast Asia, the leaves are chewed together with the mineral slaked lime (calcium hydroxide) and the areca nut which, by association, is sometimes inaccurately called the "betel nut". The lime acts to keep the active ingredient in its freebase or alkaline form, thus enabling it to enter the bloodstream via sublingual absorption. The areca nut contains the alkaloid arecoline, which promotes salivation (the saliva is stained red), and is itself a stimulant. This combination, known as a "betel quid", has been used for several thousand years. Tobacco is sometimes added.
Betel leaves are used as a stimulant, an antiseptic and a breath-freshener Paan. In Ayurvedic medicine, they are used as an aphrodisiac. In Malaysia they are used to treat headaches, arthritis and joint pain. In Thailand, Indonesia and China they are used to relieve toothache. In Indonesia they are drunk as an infusion and used as an antibiotic. They are also used in an infusion to cure indigestion, as a topical cure for constipation, as a decongestant and as an aid to lactation.
In India, betel is used to cast out (cure) worms.
In India, the betel and areca play an important role in Indian culture especially among Hindus. All the traditional ceremonies governing the lives of Hindus use betel and areca. For example to pay money to the priest, they keep money in the betel leaves and place it beside the priest.
The betel and areca also play an important role in Vietnamese culture. In Vietnamese there is a saying that "the betel begins the conversation", referring to the practice of people chewing betel in formal occasions or "to break the ice" in awkward situational conversations. The betel leaves and areca nuts are used ceremonially in traditional Vietnamese weddings. Based on a folk tale about the origins of these plants, the groom traditionally offer the bride's parents betel leaves and areca nuts (among other things) in exchange for the bride. The betel and areca are such important symbols of love and marriage such that in Vietnamese the phrase "matters of betel and areca" (chuyện trầu cau) is synonymous with marriage.
A related plant P. sarmentosum, which is used in cooking, is sometimes called "wild betel leaf".
WARNING: Chewing Betel has been associated with oral and esophageal squamous cell carcinoma.
# Further reading
- P. Guha: Betel leaf:The neglected green gold of India. J. Hum Ecol., 19(2) 2006 [1]
- U J Nair et al: Role of lime in the generation of reactive oxygen species from betel-quid ingredients.[2]
# External links
- Avandia Drug Trial for Oral Premalignant Lesions at Memorial Sloan-Kettering Cancer Center
- Sulindac Drug Trial for Oral Premalignant Lesions at Memorial Sloan-Kettering Cancer Center
- Betel news page - Alcohol and Drugs History Society
bn:পান
de:Betelpfeffer
hi:पान
id:Sirih
kn:ವೀಳ್ಯದೆಲೆ
ka:ბეტელი
nl:Betelpeper
sv:Betel (stimulantia)
ta:வெற்றிலை
tpi:Daka | https://www.wikidoc.org/index.php/Betel | |
a85078a78caf32c14b2fb6312885308280ac6a80 | wikidoc | Bevel | Bevel
A beveled edge refers to an edge of a structure that is not perpendicular (but instead often at 45 degrees) to the faces of the piece. The words bevel and chamfer overlap in usage; in general usage they are often interchanged, while in technical usage they may sometimes be differentiated as shown in the image at right.
# Applications
## Woodworking
Bevel angles can be duplicated using a sliding T bevel.
## Graphic design
Typographic bevels are shading and aritifical shadows that emulate the appearance of a 3-dimensional letter.
The bevel is a relatively common effect in graphic editors such as Photoshop. As such, it is in widespread usage in mainstream logos and archetypes.
Bevel when mentioned in the same context with boxes and squares in design refers to a raised effect, and not as commonly mistaken for rounded corners.
## Glass and mirrors
Beveled edges are a common aesthetic nicety added to window panes and mirrors.
## Geology
Geologists refer to any slope of land into a strata of different elevation as a bevel.
## Sports
In waterskiing, a bevel is the transition area between the side of the ski and the bottom of the ski. Beginners tend to prefer sharp bevels, which allow the ski to glide on the water surface.
## Cards
With a deck of cards, you can slide the top portion back so that the back of the deck is at an angle. This can be used in card tricks; see also Glossary of conjuring terms.
## Theatre
A Bevel.
Standing on one leg while pulling in the foot to the other leg.
Toe should flick out while the heel is in to the shin as far as possible. | Bevel
A beveled edge refers to an edge of a structure that is not perpendicular (but instead often at 45 degrees) to the faces of the piece. The words bevel and chamfer overlap in usage; in general usage they are often interchanged, while in technical usage they may sometimes be differentiated as shown in the image at right.
# Applications
## Woodworking
Bevel angles can be duplicated using a sliding T bevel.
## Graphic design
Typographic bevels are shading and aritifical shadows that emulate the appearance of a 3-dimensional letter.
The bevel is a relatively common effect in graphic editors such as Photoshop. As such, it is in widespread usage in mainstream logos and archetypes.
Bevel when mentioned in the same context with boxes and squares in design refers to a raised effect, and not as commonly mistaken for rounded corners.
## Glass and mirrors
Beveled edges are a common aesthetic nicety added to window panes and mirrors.
## Geology
Geologists refer to any slope of land into a strata of different elevation as a bevel.[1]
## Sports
In waterskiing, a bevel is the transition area between the side of the ski and the bottom of the ski. Beginners tend to prefer sharp bevels, which allow the ski to glide on the water surface.[2]
## Cards
With a deck of cards, you can slide the top portion back so that the back of the deck is at an angle. This can be used in card tricks; see also Glossary of conjuring terms.
## Theatre
A Bevel.
Standing on one leg while pulling in the foot to the other leg.
Toe should flick out while the heel is in to the shin as far as possible. | https://www.wikidoc.org/index.php/Bevel | |
eeb1eadfa1a40c146945b35089eb5afba31ae9d2 | wikidoc | Birch | Birch
Birch is the name of any tree of the genus Betula (Bé-tu-la), in the family Betulaceae, closely related to the beech/oak family, Fagaceae. These are generally small to medium-size trees or shrubs, mostly of northern temperate climates. The simple leaves may be toothed or lobed. The fruit is a small samara, although the wings may be obscure in some species. They differ from the alders (Alnus, the other genus in the family) in that the female catkins are not woody and disintegrate at maturity, falling apart to release the seeds, unlike the woody cone-like female alder catkins.
The common name birch is derived from an old Germanic root, birka, with the Proto-Indo-European root *bherəg, "white, bright; to shine." The Proto-Germanic rune berkanan is named after the birch. The botanic name Betula is from the original Latin. Birch is used as a food plant by the larvae of a large number of Lepidoptera (butterflies and moths) species, see List of Lepidoptera that feed on birches.
The birch is considered a national tree of Russia, where it used to be worshipped as a goddess during the Green Week in early June.
The bark of all birches is characteristically marked with long horizontal lenticels, and often separates into thin papery plates, especially upon the Paper Birch. It is practically imperishable, due to the resinous oil which it contains. Its decided color gives the common names Red, White, Black, Silver and Yellow to different species.
The buds form early and are full grown by midsummer, all are lateral, no terminal bud is formed; the branch is prolonged by the upper lateral bud. The wood of all the species is close-grained with satiny texture and capable of taking a fine polish; its fuel value is fair.
The leaves of the different species vary but little. All are alternate, doubly serrate, feather-veined, petiolate, and stipulate. Apparently they often appear in pairs, but these pairs are really borne on spur-like two-leaved lateral branchlets.
## Flower and fruit
The flowers are monoecious, opening with or before the leaves and borne on three-flowered clusters in the axils of the scales of drooping or erect aments. Staminate aments are pendulous, clustered or solitary in the axils of the last leaves of the branch of the year or near the ends of the short lateral branchlets of the year. They form in early autumn and remain rigid during the winter. The scales of the staminate aments when mature are broadly ovate, rounded, yellow or orange color below the middle, dark chestnut brown at apex. Each scale bears two bractlets and three sterile flowers, each flower consisting of a sessile, membranaceous, usually two-lobed, calyx. Each calyx bears four short filaments with one-celled anthers or strictly, two filaments divided into two branches, each bearing a half-anther. Anther cells open longitudinally. The pistillate aments (catkins) are erect or pendulous, solitary; terminal on the two-leaved lateral spur-like branchlets of the year. The pistillate scales are oblong-ovate, three-lobed, pale yellow green often tinged with red, becoming brown at maturity. These scales bear two or three fertile flowers, each flower consisting of a naked ovary. The ovary is compressed, two-celled, crowned with two slender styles; the ovule is solitary.
The ripened pistillate ament is called a strobile and bears tiny winged nuts, packed in the protecting curve of each brown and woody scale. These nuts are pale chestnut brown, compressed, crowned by the persistent stigmas. The seed fills the cavity of the nut. The cotyledons are flat and fleshy. All the species are easily grown from seed.
## Ecology
Birches often form even-aged stands on light, well-drained, particularly acidic soils. They are regarded as pioneer species, rapidly colonising open ground especially in secondary successional sequences following a disturbance or fire. Birches are early tree species to establish in primary successions and can become a threat to heathland if the seedlings and saplings are not suppressed by grazing or periodic burning. Birches are generally lowland species, but some species such as Betula nana have a montane distribution.
# Species
- Betula alleghaniensis - Yellow Birch (B. lutea)
- Betula cordifolia - Mountain Paper Birch
- Betula glandulosa - American Dwarf Birch
- Betula lenta - Sweet Birch, Cherry Birch, or Black Birch
Betula lenta subsp. uber - Virginia Round-Leaf Birch (endemic, Cressy Creek, Smyth County, Virginia)
- Betula lenta subsp. uber - Virginia Round-Leaf Birch (endemic, Cressy Creek, Smyth County, Virginia)
- Betula michauxii - Newfoundland Dwarf Birch
- Betula nana - Dwarf Birch or Bog Birch (also in northern Europe and Asia)
- Betula neoalaskana - Alaska Birch or Yukon Birch
- Betula nigra - River Birch or Black Birch
- Betula occidentalis - Water Birch or Red Birch (B. fontinalis)
- Betula papyrifera - Paper Birch, Canoe Birch or American White Birch
- Betula populifolia - Gray Birch
- Betula pubescens - Downy Birch also known as White Birch, European White Birch, Hairy Birch (Greenland; also in Europe incl. Iceland, northern Asia)
Betula pubescens subspecies tortuosa - Arctic Downy Birch (Greenland; also in subarctic Eurasia incl. Iceland)
- Betula pubescens subspecies tortuosa - Arctic Downy Birch (Greenland; also in subarctic Eurasia incl. Iceland)
- Betula pumila - Swamp Birch
- Betula albosinensis - Chinese Red Birch
Betula albosinensis var. septentrionalis - North Chinese Red Birch
- Betula albosinensis var. septentrionalis - North Chinese Red Birch
- Betula alnoides - Alder-leaf Birch
- Betula austrosinensis - South China Birch
- Betula chinensis - Chinese Dwarf Birch
- Betula ermanii - Erman's Birch
- Betula grossa - Japanese Cherry Birch
- Betula jacquemontii (Betula utilis subsp. jacquemontii) - White-barked Himalayan Birch
- Betula mandschurica - Manchurian Birch
Betula mandschurica var. japonica - Japanese Birch
- Betula mandschurica var. japonica - Japanese Birch
- Betula maximowiczii - Monarch Birch
- Betula medwediewii - Caucasian Birch
- Betula nana - Dwarf Birch (also in northern North America)
- Betula pendula - Silver Birch
- Betula platyphylla (Betula pendula var. platyphylla) - Siberian Silver Birch
- Betula pubescens - Downy Birch also known as White Birch, European White Birch, Hairy Birch (Europe incl. Iceland, northern Asia; also in Greenland in North America)
Betula pubescens subspecies tortuosa - Arctic Downy Birch (subarctic Eurasia incl. Iceland; also in Greenland in North America)
- Betula pubescens subspecies tortuosa - Arctic Downy Birch (subarctic Eurasia incl. Iceland; also in Greenland in North America)
- Betula szechuanica (Betula pendula var. szechuanica) - Sichuan Birch
- Betula utilis - Himalayan Birch
# Uses
Birch wood is fine-grained and pale in colour, often with an attractive satin-like sheen. Ripple figuring may occur, increasing the value of the timber for veneer and furniture-making. The highly-decorative Masur (or Karelian) birch, from Betula verrucosa var. carelica has ripple texture combined with attractive dark streaks and lines. Birch wood is suitable for veneer, and birch ply is among the strongest and most dimensionally-stable plywoods, although it is unsuitable for exterior use.
Due to birch pulp’s short-fibre qualities, this hardwood can be used to make printing paper. In India the thin bark coming off in winter was used as writing paper. This has excellent life. The paper is known as bhoorj patra. Bhoorj is the Sanskrit name of tree and patra means paper.
Extracts of birch are used for flavoring or leather oil, and in cosmetics such as soap or shampoo. In the past, commercial oil of wintergreen (methyl salicylate) was made from the Sweet Birch (Betula lenta). Birch tar or Russian Oil, extracted from birch bark, is thermoplastic and waterproof; it was used as a glue on, for example, arrows, and also for medicinal purposes.
Silver Birch (Betula pendula) is Finland's national tree. Occasionally one uses leafy, fragrant twigs of silver birch to gently beat oneself in a sauna. The twigs are called vihta or vasta. This has a relaxing effect on the muscles.
Birch leaves make a diuretic tea and to make extracts for dyes and cosmetics.
Ground birch bark, fermented in sea water, is used for seasoning the woolen, hemp or linen sails and hemp rope of traditional Norwegian boats.
Birch twigs were bound in a bundle, also called birch, to be used for birching, a form of corporal punishment.
Many of the First Nations of North America prized the birch for its bark, which due to its light weight, flexibility, and the ease with which it could be stripped from fallen trees, was often used for the construction of strong, waterproof but lightweight canoes, bowls, and tipis.
Birch is used as firewood due to its high calorific value per unit weight and unit volume. Birch is prized by the Sami people as it burns well, without popping, even when frozen and freshly hewn. The bark is also used in starting fires. The bark will burn very well, even when wet, because of the oils it contains. With care, the bark can be split into very thin sheets that will ignite from even the smallest of sparks.
Birches also have spiritual importance in several religions, both modern and historical.
Birch ply is made from laminations of birch veneer. It is light but strong and has many other good properties. Birch ply is used to make longboards (skateboard), giving it a strong yet flexy ride. It is also used (often in very thin grades with many laminations) for making model aircraft.
## Tonewood
Baltic Birch is among the most sought after wood in the manufacture of speaker cabinets. Birch has a natural resonance that peaks in the high and low frequencies, which are also the hardest for speakers to reproduce. This resonance compensates for the roll-off of low and high frequencies in the speakers, and evens the tone. Birch is known for having "natural EQ."
Drums are often made from Birch. Prior to the 1970s, Birch was one of the most popular drum woods. Because of the need for greater volume and midrange clarity, drums were made almost entirely from maple until recently, when advancements in live sound reinforcement and drum mics have allowed the use of Birch in high volume situations. Birch drums have a natural boost in the high and low frequencies, which allow the drums to sound fuller.
Birch wood is sometimes used as a tonewood for semi-acoustic and acoustic guitar bodies and occasionally used for solid-body guitar bodies. Birch wood is also a common material used in mallets for keyboard percussion.
## Food
In Belarus, Russia, the Baltic States, Finland, and parts of northern China, birch sap is consumed as a refreshing beverage, and is believed to have tonic qualities. It is watery and pale green in color, with a slightly sweet flavor, and is bottled commercially. Birch sap may also made into kvass. The sap of particular birch species may also be rendered into birch syrup, vinegar, birch beer (a drink similar to root beer), and other foods. In contrast to maple syrup, birch syrup is very difficult to produce, making it more expensive than other food syrups. It is also considerably less sweet than maple syrup and the sap for syrup production is not available until a month later than maple's. The syrup is made mainly in Alaska (from Alaska Birch) and Russia (from several species), and more rarely elsewhere.
Xylitol can also be extracted from birch, a sugar alcohol artificial sweetener, which has shown effectiveness in preventing, and in some cases repairing, tooth decay.
According to the Food Network series Unwrapped, birch is a preferred wood for the manufacture of toothpicks.
## Medicinal
In northern latitudes birch is considered to be the most important allergenic tree pollen, with an estimated 15-20% of hay fever sufferers sensitive to birch pollen grains.
The chaga mushroom is an adaptogen that grows on white birch trees, extracting the birch constituents and is used as a remedy for cancer.
The bark is high in betulin and betulinic acid, phytochemicals which have potential as pharmaceuticals, and other chemicals which show promise as industrial lubricants.
Birch bark can be soaked until moist in hot water, and then formed into a cast for a broken arm.
The inner bark of birch can be ingested safely. | Birch
Birch is the name of any tree of the genus Betula (Bé-tu-la), in the family Betulaceae, closely related to the beech/oak family, Fagaceae. These are generally small to medium-size trees or shrubs, mostly of northern temperate climates. The simple leaves may be toothed or lobed. The fruit is a small samara, although the wings may be obscure in some species. They differ from the alders (Alnus, the other genus in the family) in that the female catkins are not woody and disintegrate at maturity, falling apart to release the seeds, unlike the woody cone-like female alder catkins.
The common name birch is derived from an old Germanic root, birka, with the Proto-Indo-European root *bherəg, "white, bright; to shine." The Proto-Germanic rune berkanan is named after the birch. The botanic name Betula is from the original Latin. Birch is used as a food plant by the larvae of a large number of Lepidoptera (butterflies and moths) species, see List of Lepidoptera that feed on birches.
The birch is considered a national tree of Russia, where it used to be worshipped as a goddess during the Green Week in early June.
The bark of all birches is characteristically marked with long horizontal lenticels, and often separates into thin papery plates, especially upon the Paper Birch. It is practically imperishable, due to the resinous oil which it contains. Its decided color gives the common names Red, White, Black, Silver and Yellow to different species.
The buds form early and are full grown by midsummer, all are lateral, no terminal bud is formed; the branch is prolonged by the upper lateral bud. The wood of all the species is close-grained with satiny texture and capable of taking a fine polish; its fuel value is fair.
The leaves of the different species vary but little. All are alternate, doubly serrate, feather-veined, petiolate, and stipulate. Apparently they often appear in pairs, but these pairs are really borne on spur-like two-leaved lateral branchlets.[1]
## Flower and fruit
The flowers are monoecious, opening with or before the leaves and borne on three-flowered clusters in the axils of the scales of drooping or erect aments. Staminate aments are pendulous, clustered or solitary in the axils of the last leaves of the branch of the year or near the ends of the short lateral branchlets of the year. They form in early autumn and remain rigid during the winter. The scales of the staminate aments when mature are broadly ovate, rounded, yellow or orange color below the middle, dark chestnut brown at apex. Each scale bears two bractlets and three sterile flowers, each flower consisting of a sessile, membranaceous, usually two-lobed, calyx. Each calyx bears four short filaments with one-celled anthers or strictly, two filaments divided into two branches, each bearing a half-anther. Anther cells open longitudinally. The pistillate aments (catkins) are erect or pendulous, solitary; terminal on the two-leaved lateral spur-like branchlets of the year. The pistillate scales are oblong-ovate, three-lobed, pale yellow green often tinged with red, becoming brown at maturity. These scales bear two or three fertile flowers, each flower consisting of a naked ovary. The ovary is compressed, two-celled, crowned with two slender styles; the ovule is solitary.
The ripened pistillate ament is called a strobile and bears tiny winged nuts, packed in the protecting curve of each brown and woody scale. These nuts are pale chestnut brown, compressed, crowned by the persistent stigmas. The seed fills the cavity of the nut. The cotyledons are flat and fleshy. All the species are easily grown from seed.[1]
## Ecology
Birches often form even-aged stands on light, well-drained, particularly acidic soils. They are regarded as pioneer species, rapidly colonising open ground especially in secondary successional sequences following a disturbance or fire. Birches are early tree species to establish in primary successions and can become a threat to heathland if the seedlings and saplings are not suppressed by grazing or periodic burning. Birches are generally lowland species, but some species such as Betula nana have a montane distribution.
# Species
- Betula alleghaniensis - Yellow Birch (B. lutea)
- Betula cordifolia - Mountain Paper Birch
- Betula glandulosa - American Dwarf Birch
- Betula lenta - Sweet Birch, Cherry Birch, or Black Birch
Betula lenta subsp. uber - Virginia Round-Leaf Birch (endemic, Cressy Creek, Smyth County, Virginia)
- Betula lenta subsp. uber - Virginia Round-Leaf Birch (endemic, Cressy Creek, Smyth County, Virginia)
- Betula michauxii - Newfoundland Dwarf Birch
- Betula nana - Dwarf Birch or Bog Birch (also in northern Europe and Asia)
- Betula neoalaskana - Alaska Birch or Yukon Birch
- Betula nigra - River Birch or Black Birch
- Betula occidentalis - Water Birch or Red Birch (B. fontinalis)
- Betula papyrifera - Paper Birch, Canoe Birch or American White Birch
- Betula populifolia - Gray Birch
- Betula pubescens - Downy Birch also known as White Birch, European White Birch, Hairy Birch (Greenland; also in Europe incl. Iceland, northern Asia)
Betula pubescens subspecies tortuosa - Arctic Downy Birch (Greenland; also in subarctic Eurasia incl. Iceland)
- Betula pubescens subspecies tortuosa - Arctic Downy Birch (Greenland; also in subarctic Eurasia incl. Iceland)
- Betula pumila - Swamp Birch
- Betula albosinensis - Chinese Red Birch
Betula albosinensis var. septentrionalis - North Chinese Red Birch
- Betula albosinensis var. septentrionalis - North Chinese Red Birch
- Betula alnoides - Alder-leaf Birch
- Betula austrosinensis - South China Birch
- Betula chinensis - Chinese Dwarf Birch
- Betula ermanii - Erman's Birch
- Betula grossa - Japanese Cherry Birch
- Betula jacquemontii (Betula utilis subsp. jacquemontii) - White-barked Himalayan Birch
- Betula mandschurica - Manchurian Birch
Betula mandschurica var. japonica - Japanese Birch
- Betula mandschurica var. japonica - Japanese Birch
- Betula maximowiczii - Monarch Birch
- Betula medwediewii - Caucasian Birch
- Betula nana - Dwarf Birch (also in northern North America)
- Betula pendula - Silver Birch
- Betula platyphylla (Betula pendula var. platyphylla) - Siberian Silver Birch
- Betula pubescens - Downy Birch also known as White Birch, European White Birch, Hairy Birch (Europe incl. Iceland, northern Asia; also in Greenland in North America)
Betula pubescens subspecies tortuosa - Arctic Downy Birch (subarctic Eurasia incl. Iceland; also in Greenland in North America)
- Betula pubescens subspecies tortuosa - Arctic Downy Birch (subarctic Eurasia incl. Iceland; also in Greenland in North America)
- Betula szechuanica (Betula pendula var. szechuanica) - Sichuan Birch
- Betula utilis - Himalayan Birch
# Uses
Birch wood is fine-grained and pale in colour, often with an attractive satin-like sheen. Ripple figuring may occur, increasing the value of the timber for veneer and furniture-making. The highly-decorative Masur (or Karelian) birch, from Betula verrucosa var. carelica has ripple texture combined with attractive dark streaks and lines. Birch wood is suitable for veneer, and birch ply is among the strongest and most dimensionally-stable plywoods, although it is unsuitable for exterior use.
Due to birch pulp’s short-fibre qualities, this hardwood can be used to make printing paper. In India the thin bark coming off in winter was used as writing paper. This has excellent life. The paper is known as bhoorj patra. Bhoorj is the Sanskrit name of tree and patra means paper.
Extracts of birch are used for flavoring or leather oil, and in cosmetics such as soap or shampoo. In the past, commercial oil of wintergreen (methyl salicylate) was made from the Sweet Birch (Betula lenta). Birch tar or Russian Oil, extracted from birch bark[2], is thermoplastic and waterproof; it was used as a glue on, for example, arrows, and also for medicinal purposes.
Silver Birch (Betula pendula) is Finland's national tree. Occasionally one uses leafy, fragrant twigs of silver birch to gently beat oneself in a sauna. The twigs are called vihta or vasta. This has a relaxing effect on the muscles.
Birch leaves make a diuretic tea and to make extracts for dyes and cosmetics.
Ground birch bark, fermented in sea water, is used for seasoning the woolen, hemp or linen sails and hemp rope of traditional Norwegian boats.
Birch twigs were bound in a bundle, also called birch, to be used for birching, a form of corporal punishment.
Many of the First Nations of North America prized the birch for its bark, which due to its light weight, flexibility, and the ease with which it could be stripped from fallen trees, was often used for the construction of strong, waterproof but lightweight canoes, bowls, and tipis.
Birch is used as firewood due to its high calorific value per unit weight and unit volume. Birch is prized by the Sami people as it burns well, without popping, even when frozen and freshly hewn. The bark is also used in starting fires. The bark will burn very well, even when wet, because of the oils it contains. With care, the bark can be split into very thin sheets that will ignite from even the smallest of sparks.
Birches also have spiritual importance in several religions, both modern and historical.
Birch ply is made from laminations of birch veneer. It is light but strong and has many other good properties. Birch ply is used to make longboards (skateboard), giving it a strong yet flexy ride. It is also used (often in very thin grades with many laminations) for making model aircraft.
## Tonewood
Baltic Birch is among the most sought after wood in the manufacture of speaker cabinets. Birch has a natural resonance that peaks in the high and low frequencies, which are also the hardest for speakers to reproduce. This resonance compensates for the roll-off of low and high frequencies in the speakers, and evens the tone. Birch is known for having "natural EQ."
Drums are often made from Birch. Prior to the 1970s, Birch was one of the most popular drum woods. Because of the need for greater volume and midrange clarity, drums were made almost entirely from maple until recently, when advancements in live sound reinforcement and drum mics have allowed the use of Birch in high volume situations. Birch drums have a natural boost in the high and low frequencies, which allow the drums to sound fuller.
Birch wood is sometimes used as a tonewood for semi-acoustic and acoustic guitar bodies and occasionally used for solid-body guitar bodies. Birch wood is also a common material used in mallets for keyboard percussion.
## Food
In Belarus, Russia, the Baltic States, Finland, and parts of northern China, birch sap is consumed as a refreshing beverage, and is believed to have tonic qualities. It is watery and pale green in color, with a slightly sweet flavor, and is bottled commercially. Birch sap may also made into kvass. The sap of particular birch species may also be rendered into birch syrup, vinegar, birch beer (a drink similar to root beer), and other foods. In contrast to maple syrup, birch syrup is very difficult to produce, making it more expensive than other food syrups. It is also considerably less sweet than maple syrup and the sap for syrup production is not available until a month later than maple's. The syrup is made mainly in Alaska (from Alaska Birch) and Russia (from several species), and more rarely elsewhere.
Xylitol can also be extracted from birch, a sugar alcohol artificial sweetener, which has shown effectiveness in preventing, and in some cases repairing, tooth decay.
According to the Food Network series Unwrapped, birch is a preferred wood for the manufacture of toothpicks.
## Medicinal
In northern latitudes birch is considered to be the most important allergenic tree pollen, with an estimated 15-20% of hay fever sufferers sensitive to birch pollen grains.
The chaga mushroom is an adaptogen that grows on white birch trees, extracting the birch constituents and is used as a remedy for cancer.
The bark is high in betulin and betulinic acid, phytochemicals which have potential as pharmaceuticals, and other chemicals which show promise as industrial lubricants.
Birch bark can be soaked until moist in hot water, and then formed into a cast for a broken arm[citation needed].
The inner bark of birch can be ingested safely. | https://www.wikidoc.org/index.php/Birch | |
41032383239eea9b5d76c13dae98348ae5e061dd | wikidoc | Blink | Blink
Blinking is the rapid closing and opening of the eyelid. It is an essential function of the eye that helps spread tears across and remove irritants from the surface of the cornea and conjunctiva. On average, a blink takes approximately 300 to 400 milliseconds. Blink speed can be affected by elements such as fatigue, eye injury, medication, and disease. A person approximately blinks once every two to ten seconds. The blinking rate is determined by the "blinking center", but it can also be affected by external stimulus. When an animal (usually human) chooses to blink only one eye as a signal to another in a social setting (a form of body language), it is known as winking. However, some animals (for example, tortoises and hamsters) blink their eyes independently of each other.
# Function and anatomy of blinking
Blinking provides moisture to the eye by irrigation using tears and a lubricant the eyes secrete. The eyelid provides suction across the eye from the tear duct to the entire eyeball to keep it from drying out.
Blinking also protects the eye from irritants. Eyelashes are hairs attached to the upper and lower eyelids that create a line of defense against dust and other elements to the eye. The eyelashes catch most of these irritants before they reach the eyeball.
There are multiple muscles that control the reflex of blinking. The main muscles, in the upper eyelid, that control the opening and closing are the orbicularis oculi and levator palpebrae superioris muscle. The orbicularis oculi closes the eye, while the relaxation and contraction of the levator palpebrae muscle opens the eye. The Müller’s muscle, or the superior palpebral muscle, in the upper eyelid and the inferior palpebral muscle in the lower eyelid are responsible for widening the eyes. These muscles are not only imperative in blinking, but they are also important in many other functions such as squinting and winking.
# Blinking in everyday life
Infants do not blink at the same rate of adults; in fact infants only blink at an average rate of one or two times in a minute. The reason for this difference is unknown, but it is suggested that babies do not require the same amount of eye lubrication that adults do because their eyelid opening is smaller in relation to adults. Additionally, infants do not produce tears during their first month of life. Babies also get a significant amount more sleep than adults do, and, as discussed earlier, fatigued eyes blink more. However, throughout childhood the blink rate increases, and by adolescence, it is usually equivalent to adults.
Women and men do not differ in their rates of spontaneous blinking, averaging around 10 blinks per minute in a laboratory setting. However, when the eyes are focused on object for an extended period of time, such as when reading, the rate of blinking decreases to about 3-4 times per minute. This is the major reason that eyes dry out and become fatigued when reading.
Eye blinking can be a criterion for diagnosing medical conditions. For example, excessive blinking may help to indicate the onset of Tourette syndrome, strokes or disorders of the nervous system. A reduced rate of blinking is associated with Parkinson's disease. Parkinson's patients have a distinct, serpentine stare that is very recognisable. | Blink
Blinking is the rapid closing and opening of the eyelid. It is an essential function of the eye that helps spread tears across and remove irritants from the surface of the cornea and conjunctiva. On average, a blink takes approximately 300 to 400 milliseconds.[1] Blink speed can be affected by elements such as fatigue, eye injury, medication, and disease. A person approximately blinks once every two to ten seconds. The blinking rate is determined by the "blinking center", but it can also be affected by external stimulus. When an animal (usually human) chooses to blink only one eye as a signal to another in a social setting (a form of body language), it is known as winking. However, some animals (for example, tortoises and hamsters) blink their eyes independently of each other.
# Function and anatomy of blinking
Blinking provides moisture to the eye by irrigation using tears and a lubricant the eyes secrete. The eyelid provides suction across the eye from the tear duct to the entire eyeball to keep it from drying out.
Blinking also protects the eye from irritants. Eyelashes are hairs attached to the upper and lower eyelids that create a line of defense against dust and other elements to the eye. The eyelashes catch most of these irritants before they reach the eyeball.
There are multiple muscles that control the reflex of blinking. The main muscles, in the upper eyelid, that control the opening and closing are the orbicularis oculi and levator palpebrae superioris muscle. The orbicularis oculi closes the eye, while the relaxation and contraction of the levator palpebrae muscle opens the eye. The Müller’s muscle, or the superior palpebral muscle, in the upper eyelid and the inferior palpebral muscle in the lower eyelid are responsible for widening the eyes. These muscles are not only imperative in blinking, but they are also important in many other functions such as squinting and winking.
# Blinking in everyday life
Infants do not blink at the same rate of adults; in fact infants only blink at an average rate of one or two times in a minute. The reason for this difference is unknown, but it is suggested that babies do not require the same amount of eye lubrication that adults do because their eyelid opening is smaller in relation to adults. Additionally, infants do not produce tears during their first month of life. Babies also get a significant amount more sleep than adults do, and, as discussed earlier, fatigued eyes blink more. However, throughout childhood the blink rate increases, and by adolescence, it is usually equivalent to adults.[2]
Women and men do not differ in their rates of spontaneous blinking,[3] averaging around 10 blinks per minute in a laboratory setting. However, when the eyes are focused on object for an extended period of time, such as when reading, the rate of blinking decreases to about 3-4 times per minute. This is the major reason that eyes dry out and become fatigued when reading.
Eye blinking can be a criterion for diagnosing medical conditions. For example, excessive blinking may help to indicate the onset of Tourette syndrome, strokes or disorders of the nervous system. A reduced rate of blinking is associated with Parkinson's disease. Parkinson's patients have a distinct, serpentine stare that is very recognisable. | https://www.wikidoc.org/index.php/Blink | |
539691ce98fc723cf66f25b4ffbe6b1bf232043a | wikidoc | Blood | Blood
# Overview
Blood is a specialized biological fluid consisting of red blood cells (also called RBCs or erythrocytes), white blood cells (also called leukocytes) and platelets (also called thrombocytes) suspended in a complex fluid medium known as blood plasma.
By far the most abundant cells in blood are red blood cells. These contain hemoglobin which gives blood its red color. The iron-containing heme portion of Hemoglobin facilitates hemoglobin-bound transportation of oxygen and carbon dioxide by selectively binding to these respiratory gasses and greatly increasing their solubility in blood. White blood cells help to resist infections, and platelets are important in the clotting of blood.
Blood is circulated around the body through blood vessels by the pumping action of the heart. Blood is pumped from the strong left ventricle of the heart through arteries to peripheral tissues and returns to the right atrium of the heart through veins, blood then enters the right ventricle and is pumped through the pulmonary artery to the lungs and returns to the left atrium through the pulmonary veins, blood then enters the left ventricle to be circulated again. Arterial blood carries oxygen from inhaled air in the lungs to all of the cells of the body, and venous blood carries carbon dioxide, produced as a waste product of metabolism by cells, to the lungs to be exhaled.
Medical terms related to blood often begin with hemo- or hemato- (BE: haemo- and haemato-) from the Greek word "haima" for "blood." Anatomically, blood is considered a connective tissue from both its origin in the bones and its function.
# Functions
- Supply of oxygen to tissues (bound to hemoglobin which is carried in red cells)
- Supply of nutrients such as glucose, amino acids and fatty acids (dissolved in the blood or bound to plasma proteins)
- Removal of waste such as carbon dioxide, urea and lactic acid
- Immunological functions, including circulation of white cells, and detection of foreign material by antibodies
- Coagulation, which is one part of the body's self-repair mechanism
- Messenger functions, including the transport of hormones and the signalling of tissue damage
- Regulation of body pH (the normal pH of blood is in the range of 7.35 - 7.45)
- Regulation of core body temperature
- Hydraulic functions
Problems with blood composition or circulation can lead to downstream tissue dysfunction. The term ischaemia refers to tissue which is inadequately perfused with blood.
The blood is circulated around the lungs and body by the pumping action of the heart. Additional return pressure may be generated by gravity and the actions of skeletal muscles. In mammals, blood is in equilibrium with lymph, which is continuously formed from blood (by capillary ultrafiltration) and returned to the blood (via the thoracic duct). The lymphatic circulation may be thought of as the "second circulation".
# Constituents of human blood
Blood accounts for 7% of the human body weight, with an average density of approximately 1060 kg/m³, very close to pure water's density of 1000 kg/m3 The average adult has a blood volume of roughly 5 litres, composed of plasma (see below) and several kinds of cells (occasionally called corpuscles); these formed elements of the blood are erythrocytes (red blood cells), leukocytes (white blood cells), and thrombocytes (platelets). The red blood cells constitute about 45% of whole blood by volume.
Each litre of blood contains:
- 5 × 1012 erythrocytes (45.0% of blood volume) : In mammals, mature red blood cells lack a nucleus and organelles. They contain the blood's hemoglobin and distribute oxygen. The red blood cells (together with endothelial vessel cells and some other cells) are also marked by glycoproteins that define the different blood types. The proportion of blood occupied by red blood cells is referred to as the hematocrit. The combined surface area of all the red cells in the human body would be roughly 2,000 times as great as the body's exterior surface.
- 9 × 109 leukocytes (1.0% of blood volume) : White blood cells are part of the immune system; they destroy and remove old or aberrant cells and cellular debris, as well as attack infectious agents (pathogens) and foreign substances.
- 3 × 1011 thrombocytes (<1.0% of blood volume) : Platelets are responsible for blood clotting (coagulation). They change fibrinogen into fibrin. This fibrin creates a mesh onto which red blood cells collect and clot. This clot stops more blood from leaving the body and also helps to prevent bacteria from entering the body.
The other 55% (making up a total of 2.7-3.0 litres in an average human) is blood plasma, a fluid that is the blood's liquid medium, appearing golden-yellow in color. Blood plasma is essentially an aqueous solution containing 92% water, 8% blood plasma proteins, and trace amounts of other materials. Some components are:
- Serum albumin
- Blood clotting factors (to facilitate coagulation)
- Immunoglobulins (antibodies)
- Hormones
- Carbon dioxide
- Various other proteins
- Various electrolytes (mainly sodium and chloride)
Together, plasma and cells form a non-Newtonian fluid whose flow properties are uniquely adapted to the architecture of the blood vessels. The term serum refers to plasma from which the clotting proteins have been removed. Most of the protein remaining is albumin and immunoglobulins.
The normal pH of human arterial blood is approximately 7.40 (normal range is 7.35-7.45), a weak alkaline solution. Blood that has a pH below 7.35 is considered overly acidic, while blood pH above 7.45 is too alkaline. Blood pH along with arterial carbon dioxide tension (PaCO2) and HCO3 readings are helpful in determining the acid-base balance of the body. The respiratory system and urinary system normally control the acid-base balance of blood as part of homeostasis.
# Physiology
## Production and degradation
Blood cells are produced in the bone marrow; this process is termed hematopoiesis. The proteinaceous component (including clotting proteins) is produced overwhelmingly in the liver, while hormones are produced by the endocrine glands and the watery fraction is regulated by the hypothalamus and maintained by the kidney and indirectly by the gut.
Blood cells are degraded by the spleen and the Kupffer cells in the liver. The liver also clears some proteins, lipids and amino acids. The kidney actively secretes waste products into the urine. Healthy erythrocytes have a plasma half-life of 120 days before they are systematically replaced by new erythrocytes created by the process of hematopoiesis.
## Transport of oxygen
Blood oxygenation is measured in several ways, but the most important measure is the hemoglobin (Hb) saturation percentage. This is a non-linear (sigmoidal) function of the partial pressure of oxygen. About 98.5% of the oxygen in a sample of arterial blood in a healthy human breathing air at normal pressure is chemically combined with the Hb. Only 1.5% is physically dissolved in the other blood liquids and not connected to Hb. The hemoglobin molecule is the primary transporter of oxygen in mammals and many other species (for exceptions, see below).
With the exception of pulmonary and umbilical arteries and their corresponding veins, arteries carry oxygenated blood away from the heart and deliver it to the body via arterioles and capillaries, where the oxygen is consumed; afterwards, venules and veins carry deoxygenated blood back to the heart.
Differences in infrared absorption between oxygenated and deoxygenated blood form the basis for realtime oxygen saturation measurement in hospitals and ambulances.
Under normal conditions in humans at rest, hemoglobin in blood leaving the lungs is about 98-99% saturated with oxygen. In a healthy adult at rest, deoxygenated blood returning to the lungs is still approximately 75% saturated. Increased oxygen consumption during sustained exercise reduces the oxygen saturation of venous blood, which can reach less than 15% in a trained athlete; although breathing rate and blood flow increase to compensate, oxygen saturation in arterial blood can drop to 95% or less under these conditions. Oxygen saturation this low is considered dangerous in an individual at rest (for instance, during surgery under anesthesia): "As a general rule, any condition which leads to a sustained mixed venous saturation of less than 50% will be poorly tolerated and a mixed venous saturation of less than 30% should be viewed as a medical emergency."
A fetus, receiving oxygen via the placenta, is exposed to much lower oxygen pressures (about 21% of the level found in an adult's lungs) and so fetuses produce another form of hemoglobin with a much higher affinity for oxygen (hemoglobin F) in order to function under these conditions.
Substances other than oxygen can bind to the hemoglobin; in some cases this can cause irreversible damage to the body. Carbon monoxide for example is extremely dangerous when absorbed into the blood. When combined with the hemoglobin, it irreversibly makes carboxyhemoglobin which reduces the volume of oxygen that can be carried in the blood. This can very quickly cause suffocation, as oxygen is vital to many organisms (including humans). This damage can occur when smoking a cigarette (or similar item) or in event of a fire. Thus carbon monoxide is considered far more dangerous than the actual fire itself because it reduces the oxygen carrying content of the blood.
### Invertebrates
In insects, the blood (more properly called hemolymph) is not involved in the transport of oxygen. (Openings called tracheae allow oxygen from the air to diffuse directly to the tissues). Insect blood moves nutrients to the tissues and removes waste products in an open system.
Other invertebrates use respiratory proteins to increase the oxygen carrying capacity. Hemoglobin is the most common respiratory protein found in nature. Hemocyanin (blue) contains copper and is found in crustaceans and mollusks. It is thought that tunicates (sea squirts) might use vanabins (proteins containing vanadium) for respiratory pigment (bright green, blue, or orange).
In many invertebrates, these oxygen-carrying proteins are freely soluble in the blood; in vertebrates they are contained in specialized red blood cells, allowing for a higher concentration of respiratory pigments without increasing viscosity or damaging blood filtering organs like the kidneys.
Giant tube worms have extraordinary hemoglobins that allow them to live in extraordinary environments. These hemoglobins also carry sulfides normally fatal in other animals.
## Transport of carbon dioxide
When systemic arterial blood flows through capillaries, carbon dioxide diffuses from the tissues into the blood. Some carbon dioxide is dissolved in the blood. Some carbon dioxide reacts with hemoglobin and other proteins to form carbamino compounds. The remaining carbon dioxide is converted to bicarbonate and hydrogen ions through the action of RBC carbonic anhydrase. Most carbon dioxide is transported through the blood in the form of bicarbonate ions.
## Transport of hydrogen ions
Some oxyhemoglobin loses oxygen and becomes deoxyhemoglobin. Deoxyhemoglobin has a much greater affinity for hydrogen ion (H+) than does oxyhemoglobin so it binds most of the hydrogen ions.
## Thermoregulation
Blood circulation transports heat through the body, and adjustments to this flow are an important part of thermoregulation. Increasing blood flow to the surface (e.g. during warm weather or strenuous exercise) causes warmer skin, resulting in faster heat loss, while decreasing surface blood flow conserves heat.
## Hydraulic functions
The restriction of blood flow can also be used in specialized tissues to cause engorgement resulting in an erection of that tissue. Examples of this would occur in a mammalian penis, clitoris or nipple.
Another example of a hydraulic function is the jumping spider, in which blood forced into the legs under pressure causes them to straighten for a powerful jump.
## Color
In humans and other hemoglobin-using creatures, oxygenated blood is bright red. This is due to oxygenated iron-containing hemoglobin found in the red blood cells. Deoxygenated blood is a darker shade of red, which can be seen during blood donation and when venous blood samples are taken.
The blood of most molluscs, and some arthropods such as horseshoe crabs, is blue. This is a result of its high content of copper-based hemocyanin instead of the iron-based hemoglobin found, for example, in mammals. While mammalian blood is never blue, there is a rare condition (sulfhemoglobinemia) that results in green blood. Skinks in the genus Prasinohaema have green blood due to a buildup of the waste product biliverdin.
# Health and disease
## Ancient medicine
Hippocratic medicine considered blood one of the four humors (together with phlegm, yellow bile and black bile). As many diseases were thought to be due to an excess of blood, bloodletting and leeching were a common intervention until the 19th century (it is still used for some rare blood disorders).
In classical Greek medicine, blood was associated with air, springtime, and with a merry and gluttonous (sanguine) personality. It was also believed to be produced exclusively by the liver.
## Diagnosis
Blood pressure and blood tests are amongst the most commonly performed diagnostic investigations that directly concern the blood.
## Pathology
Problems with blood circulation and composition play a role in many diseases.
- Wounds can cause major blood loss (see bleeding). The thrombocytes cause the blood to coagulate, blocking relatively minor wounds, but larger ones must be repaired at speed to prevent exsanguination. Damage to the internal organs can cause severe internal bleeding, or hemorrhage.
- Circulation blockage can also create many medical conditions from ischemia in the short term to tissue necrosis and gangrene in the long term.
- Hemophilia is a genetic illness that causes dysfunction in one of the blood's clotting mechanisms. This can allow otherwise inconsequential wounds to be life-threatening, but more commonly results in hemarthrosis, or bleeding into joint spaces, which can be crippling.
- Leukemia is a group of cancers of the blood-forming tissues.
- Major blood loss, whether traumatic or not (e.g. during surgery), as well as certain blood diseases like anemia and thalassemia, can require blood transfusion. Several countries have blood banks to fill the demand for transfusable blood. A person receiving a blood transfusion must have a blood type compatible with that of the donor.
- Overproduction of red blood cells is called polycythemia.
- Blood is an important vector of infection. HIV, the virus which causes AIDS, is transmitted through contact between blood, semen, or the bodily secretions of an infected person. Hepatitis B and C are transmitted primarily through blood contact. Owing to blood-borne infections, bloodstained objects are treated as a biohazard.
- Bacterial infection of the blood is bacteremia or sepsis. Viral Infection is viremia. Malaria and trypanosomiasis are blood-borne parasitic infections.
## Treatment
Blood transfusion is the most direct therapeutic use of blood. It is obtained from human donors by blood donation. As there are different blood types, and transfusion of the incorrect blood may cause severe complications, crossmatching is done to ascertain the correct type is transfused.
Other blood products administered intravenously are platelets, blood plasma, cryoprecipitate and specific coagulation factor concentrates.
Many forms of medication (from antibiotics to chemotherapy) are administered intravenously, as they are not readily or adequately absorbed by the digestive tract.
As stated above, some diseases are still treated by removing blood from the circulation, eg. haemochromatosis.
It is the fluid part of the blood that saves lives where severe blood loss occurs, other preparations can be given such as ringers atopical plasma volume expander as a non-blood alternative, and these alternatives where used are rivalling blood use when used. | Blood
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
# Overview
Blood is a specialized biological fluid consisting of red blood cells (also called RBCs or erythrocytes), white blood cells (also called leukocytes) and platelets (also called thrombocytes) suspended in a complex fluid medium known as blood plasma.
By far the most abundant cells in blood are red blood cells. These contain hemoglobin which gives blood its red color. The iron-containing heme portion of Hemoglobin facilitates hemoglobin-bound transportation of oxygen and carbon dioxide by selectively binding to these respiratory gasses and greatly increasing their solubility in blood. White blood cells help to resist infections, and platelets are important in the clotting of blood.
Blood is circulated around the body through blood vessels by the pumping action of the heart. Blood is pumped from the strong left ventricle of the heart through arteries to peripheral tissues and returns to the right atrium of the heart through veins, blood then enters the right ventricle and is pumped through the pulmonary artery to the lungs and returns to the left atrium through the pulmonary veins, blood then enters the left ventricle to be circulated again. Arterial blood carries oxygen from inhaled air in the lungs to all of the cells of the body, and venous blood carries carbon dioxide, produced as a waste product of metabolism by cells, to the lungs to be exhaled.
Medical terms related to blood often begin with hemo- or hemato- (BE: haemo- and haemato-) from the Greek word "haima" for "blood." Anatomically, blood is considered a connective tissue from both its origin in the bones and its function.
# Functions
- Supply of oxygen to tissues (bound to hemoglobin which is carried in red cells)
- Supply of nutrients such as glucose, amino acids and fatty acids (dissolved in the blood or bound to plasma proteins)
- Removal of waste such as carbon dioxide, urea and lactic acid
- Immunological functions, including circulation of white cells, and detection of foreign material by antibodies
- Coagulation, which is one part of the body's self-repair mechanism
- Messenger functions, including the transport of hormones and the signalling of tissue damage
- Regulation of body pH (the normal pH of blood is in the range of 7.35 - 7.45)
- Regulation of core body temperature
- Hydraulic functions
Problems with blood composition or circulation can lead to downstream tissue dysfunction. The term ischaemia refers to tissue which is inadequately perfused with blood.
The blood is circulated around the lungs and body by the pumping action of the heart. Additional return pressure may be generated by gravity and the actions of skeletal muscles. In mammals, blood is in equilibrium with lymph, which is continuously formed from blood (by capillary ultrafiltration) and returned to the blood (via the thoracic duct). The lymphatic circulation may be thought of as the "second circulation".
# Constituents of human blood
Blood accounts for 7% of the human body weight[1], with an average density of approximately 1060 kg/m³, very close to pure water's density of 1000 kg/m3[2] The average adult has a blood volume of roughly 5 litres, composed of plasma (see below) and several kinds of cells (occasionally called corpuscles); these formed elements of the blood are erythrocytes (red blood cells), leukocytes (white blood cells), and thrombocytes (platelets). The red blood cells constitute about 45% of whole blood by volume.
Each litre of blood contains:[1]
- 5 × 1012 erythrocytes (45.0% of blood volume) : In mammals, mature red blood cells lack a nucleus and organelles. They contain the blood's hemoglobin and distribute oxygen. The red blood cells (together with endothelial vessel cells and some other cells) are also marked by glycoproteins that define the different blood types. The proportion of blood occupied by red blood cells is referred to as the hematocrit. The combined surface area of all the red cells in the human body would be roughly 2,000 times as great as the body's exterior surface.[3]
- 9 × 109 leukocytes (1.0% of blood volume) : White blood cells are part of the immune system; they destroy and remove old or aberrant cells and cellular debris, as well as attack infectious agents (pathogens) and foreign substances.
- 3 × 1011 thrombocytes (<1.0% of blood volume) : Platelets are responsible for blood clotting (coagulation). They change fibrinogen into fibrin. This fibrin creates a mesh onto which red blood cells collect and clot. This clot stops more blood from leaving the body and also helps to prevent bacteria from entering the body.
The other 55% (making up a total of 2.7-3.0 litres in an average human) is blood plasma, a fluid that is the blood's liquid medium, appearing golden-yellow in color. Blood plasma is essentially an aqueous solution containing 92% water, 8% blood plasma proteins, and trace amounts of other materials. Some components are:
- Serum albumin
- Blood clotting factors (to facilitate coagulation)
- Immunoglobulins (antibodies)
- Hormones
- Carbon dioxide
- Various other proteins
- Various electrolytes (mainly sodium and chloride)
Together, plasma and cells form a non-Newtonian fluid whose flow properties are uniquely adapted to the architecture of the blood vessels. The term serum refers to plasma from which the clotting proteins have been removed. Most of the protein remaining is albumin and immunoglobulins.
The normal pH of human arterial blood is approximately 7.40 (normal range is 7.35-7.45), a weak alkaline solution. Blood that has a pH below 7.35 is considered overly acidic, while blood pH above 7.45 is too alkaline. Blood pH along with arterial carbon dioxide tension (PaCO2) and HCO3 readings are helpful in determining the acid-base balance of the body. The respiratory system and urinary system normally control the acid-base balance of blood as part of homeostasis.
# Physiology
## Production and degradation
Blood cells are produced in the bone marrow; this process is termed hematopoiesis. The proteinaceous component (including clotting proteins) is produced overwhelmingly in the liver, while hormones are produced by the endocrine glands and the watery fraction is regulated by the hypothalamus and maintained by the kidney and indirectly by the gut.
Blood cells are degraded by the spleen and the Kupffer cells in the liver. The liver also clears some proteins, lipids and amino acids. The kidney actively secretes waste products into the urine. Healthy erythrocytes have a plasma half-life of 120 days before they are systematically replaced by new erythrocytes created by the process of hematopoiesis.
## Transport of oxygen
Blood oxygenation is measured in several ways, but the most important measure is the hemoglobin (Hb) saturation percentage. This is a non-linear (sigmoidal) function of the partial pressure of oxygen. About 98.5% of the oxygen in a sample of arterial blood in a healthy human breathing air at normal pressure is chemically combined with the Hb. Only 1.5% is physically dissolved in the other blood liquids and not connected to Hb. The hemoglobin molecule is the primary transporter of oxygen in mammals and many other species (for exceptions, see below).
With the exception of pulmonary and umbilical arteries and their corresponding veins, arteries carry oxygenated blood away from the heart and deliver it to the body via arterioles and capillaries, where the oxygen is consumed; afterwards, venules and veins carry deoxygenated blood back to the heart.
Differences in infrared absorption between oxygenated and deoxygenated blood form the basis for realtime oxygen saturation measurement in hospitals and ambulances.
Under normal conditions in humans at rest, hemoglobin in blood leaving the lungs is about 98-99% saturated with oxygen. In a healthy adult at rest, deoxygenated blood returning to the lungs is still approximately 75% saturated.[4][5] Increased oxygen consumption during sustained exercise reduces the oxygen saturation of venous blood, which can reach less than 15% in a trained athlete; although breathing rate and blood flow increase to compensate, oxygen saturation in arterial blood can drop to 95% or less under these conditions.[6] Oxygen saturation this low is considered dangerous in an individual at rest (for instance, during surgery under anesthesia): "As a general rule, any condition which leads to a sustained mixed venous saturation of less than 50% will be poorly tolerated and a mixed venous saturation of less than 30% should be viewed as a medical emergency."[7]
A fetus, receiving oxygen via the placenta, is exposed to much lower oxygen pressures (about 21% of the level found in an adult's lungs) and so fetuses produce another form of hemoglobin with a much higher affinity for oxygen (hemoglobin F) in order to function under these conditions.[8]
Substances other than oxygen can bind to the hemoglobin; in some cases this can cause irreversible damage to the body. Carbon monoxide for example is extremely dangerous when absorbed into the blood. When combined with the hemoglobin, it irreversibly makes carboxyhemoglobin which reduces the volume of oxygen that can be carried in the blood. This can very quickly cause suffocation, as oxygen is vital to many organisms (including humans). This damage can occur when smoking a cigarette (or similar item) or in event of a fire. Thus carbon monoxide is considered far more dangerous than the actual fire itself because it reduces the oxygen carrying content of the blood.
### Invertebrates
In insects, the blood (more properly called hemolymph) is not involved in the transport of oxygen. (Openings called tracheae allow oxygen from the air to diffuse directly to the tissues). Insect blood moves nutrients to the tissues and removes waste products in an open system.
Other invertebrates use respiratory proteins to increase the oxygen carrying capacity. Hemoglobin is the most common respiratory protein found in nature. Hemocyanin (blue) contains copper and is found in crustaceans and mollusks. It is thought that tunicates (sea squirts) might use vanabins (proteins containing vanadium) for respiratory pigment (bright green, blue, or orange).
In many invertebrates, these oxygen-carrying proteins are freely soluble in the blood; in vertebrates they are contained in specialized red blood cells, allowing for a higher concentration of respiratory pigments without increasing viscosity or damaging blood filtering organs like the kidneys.
Giant tube worms have extraordinary hemoglobins that allow them to live in extraordinary environments. These hemoglobins also carry sulfides normally fatal in other animals.
## Transport of carbon dioxide
When systemic arterial blood flows through capillaries, carbon dioxide diffuses from the tissues into the blood. Some carbon dioxide is dissolved in the blood. Some carbon dioxide reacts with hemoglobin and other proteins to form carbamino compounds. The remaining carbon dioxide is converted to bicarbonate and hydrogen ions through the action of RBC carbonic anhydrase. Most carbon dioxide is transported through the blood in the form of bicarbonate ions.
## Transport of hydrogen ions
Some oxyhemoglobin loses oxygen and becomes deoxyhemoglobin. Deoxyhemoglobin has a much greater affinity for hydrogen ion (H+) than does oxyhemoglobin so it binds most of the hydrogen ions.
## Thermoregulation
Blood circulation transports heat through the body, and adjustments to this flow are an important part of thermoregulation. Increasing blood flow to the surface (e.g. during warm weather or strenuous exercise) causes warmer skin, resulting in faster heat loss, while decreasing surface blood flow conserves heat.
## Hydraulic functions
The restriction of blood flow can also be used in specialized tissues to cause engorgement resulting in an erection of that tissue. Examples of this would occur in a mammalian penis, clitoris or nipple.
Another example of a hydraulic function is the jumping spider, in which blood forced into the legs under pressure causes them to straighten for a powerful jump.
## Color
In humans and other hemoglobin-using creatures, oxygenated blood is bright red. This is due to oxygenated iron-containing hemoglobin found in the red blood cells. Deoxygenated blood is a darker shade of red, which can be seen during blood donation and when venous blood samples are taken.
The blood of most molluscs, and some arthropods such as horseshoe crabs, is blue. This is a result of its high content of copper-based hemocyanin instead of the iron-based hemoglobin found, for example, in mammals. While mammalian blood is never blue, there is a rare condition (sulfhemoglobinemia) that results in green blood. Skinks in the genus Prasinohaema have green blood due to a buildup of the waste product biliverdin.
# Health and disease
## Ancient medicine
Hippocratic medicine considered blood one of the four humors (together with phlegm, yellow bile and black bile). As many diseases were thought to be due to an excess of blood, bloodletting and leeching were a common intervention until the 19th century (it is still used for some rare blood disorders).
In classical Greek medicine, blood was associated with air, springtime, and with a merry and gluttonous (sanguine) personality. It was also believed to be produced exclusively by the liver.
## Diagnosis
Blood pressure and blood tests are amongst the most commonly performed diagnostic investigations that directly concern the blood.
## Pathology
Template:Seealso
Problems with blood circulation and composition play a role in many diseases.
- Wounds can cause major blood loss (see bleeding). The thrombocytes cause the blood to coagulate, blocking relatively minor wounds, but larger ones must be repaired at speed to prevent exsanguination. Damage to the internal organs can cause severe internal bleeding, or hemorrhage.
- Circulation blockage can also create many medical conditions from ischemia in the short term to tissue necrosis and gangrene in the long term.
- Hemophilia is a genetic illness that causes dysfunction in one of the blood's clotting mechanisms. This can allow otherwise inconsequential wounds to be life-threatening, but more commonly results in hemarthrosis, or bleeding into joint spaces, which can be crippling.
- Leukemia is a group of cancers of the blood-forming tissues.
- Major blood loss, whether traumatic or not (e.g. during surgery), as well as certain blood diseases like anemia and thalassemia, can require blood transfusion. Several countries have blood banks to fill the demand for transfusable blood. A person receiving a blood transfusion must have a blood type compatible with that of the donor.
- Overproduction of red blood cells is called polycythemia.
- Blood is an important vector of infection. HIV, the virus which causes AIDS, is transmitted through contact between blood, semen, or the bodily secretions of an infected person. Hepatitis B and C are transmitted primarily through blood contact. Owing to blood-borne infections, bloodstained objects are treated as a biohazard.
- Bacterial infection of the blood is bacteremia or sepsis. Viral Infection is viremia. Malaria and trypanosomiasis are blood-borne parasitic infections.
## Treatment
Blood transfusion is the most direct therapeutic use of blood. It is obtained from human donors by blood donation. As there are different blood types, and transfusion of the incorrect blood may cause severe complications, crossmatching is done to ascertain the correct type is transfused.
Other blood products administered intravenously are platelets, blood plasma, cryoprecipitate and specific coagulation factor concentrates.
Many forms of medication (from antibiotics to chemotherapy) are administered intravenously, as they are not readily or adequately absorbed by the digestive tract.
As stated above, some diseases are still treated by removing blood from the circulation, eg. haemochromatosis.
It is the fluid part of the blood that saves lives where severe blood loss occurs, other preparations can be given such as ringers atopical plasma volume expander as a non-blood alternative, and these alternatives where used are rivalling blood use when used. | https://www.wikidoc.org/index.php/Blood | |
cd90b326a720702b401de85a3feca509d8e1013e | wikidoc | Boldo | Boldo
Boldo (Peumus boldus Molina, the only species in the genus Peumus) is a tree native to the central region of Chile. Together with litre, quillay, peumo, bollén and other indigenous plants, it is a characteristic component of the sclerophyllous forest (hard leaves that resist long dry summers and cold rainy winters) endemic to central Chile. Its leaves, which have a strong, woody and slightly bitter flavor and camphor-like aroma, are used for culinary purposes, primarily in Latin America. The leaves are used in a similar manner to bay leaves, and also used as an herbal tea, primarily in Chile and Argentina but also in other Spanish-speaking nations, and Brazil.
Not too well known, but very tasty and nutritious, Boldo fruits, which appear between December and February, are small green edible spheres that contain lots of sugars and aid the traveler for refreshing himself on those sunny and dry days.
Boldo's assertive flavor comes primarily from the presence of the chemical ascaridol, which is also present in the epazote plant.
In Latin America and Spain, boldo is also used as a form of herbal medicine, particularly to support the gallbladder, but also to calm upset stomachs. In Chile, it is frequently mixed with yerba mate or other teas to moderate its flavor. In Brazil, many families keep a boldo plant at home for this purpose, although boldo teabags are readily available in nearly all supermarkets.
Boldo is in the family Monimiaceae, which is closely related to the family Lauraceae (which includes many other plants used for their aromatic leaves, such as cinnamon, cassia, bay leaf, and camphor laurel.
Boldo has also been introduced to Europe and North Africa. | Boldo
Boldo (Peumus boldus Molina, the only species in the genus Peumus) is a tree native to the central region of Chile. Together with litre, quillay, peumo, bollén and other indigenous plants, it is a characteristic component of the sclerophyllous forest (hard leaves that resist long dry summers and cold rainy winters) endemic to central Chile. Its leaves, which have a strong, woody and slightly bitter flavor and camphor-like aroma, are used for culinary purposes, primarily in Latin America. The leaves are used in a similar manner to bay leaves, and also used as an herbal tea, primarily in Chile and Argentina but also in other Spanish-speaking nations, and Brazil.
Not too well known, but very tasty and nutritious, Boldo fruits, which appear between December and February, are small green edible spheres that contain lots of sugars and aid the traveler for refreshing himself on those sunny and dry days.
Boldo's assertive flavor comes primarily from the presence of the chemical ascaridol, which is also present in the epazote plant.
In Latin America and Spain, boldo is also used as a form of herbal medicine, particularly to support the gallbladder, but also to calm upset stomachs. In Chile, it is frequently mixed with yerba mate or other teas to moderate its flavor. In Brazil, many families keep a boldo plant at home for this purpose, although boldo teabags are readily available in nearly all supermarkets.
Boldo is in the family Monimiaceae, which is closely related to the family Lauraceae (which includes many other plants used for their aromatic leaves, such as cinnamon, cassia, bay leaf, and camphor laurel.
Boldo has also been introduced to Europe and North Africa.
# External links
- Boldo leaves (Peumus boldus Molina) page at Gernot Katzer's Spice Pages
- Boldo Uses
- Pictures and information of Boldo tree, leaves and flowers
Template:Herbs & spices
Template:Fruit-tree-stub
bg:Болдо
de:Boldo
it:Peumus boldus | https://www.wikidoc.org/index.php/Boldo | |
99f9333e22790846d14366e57c2c7369b3fbe370 | wikidoc | Borax | Borax
Borax (from Persian burah), also known as sodium borate, sodium tetraborate, or disodium tetraborate, is an important boron compound, a mineral, and a salt of boric acid. It is usually a white powder consisting of soft colorless crystals that dissolve easily in water.
Borax has a wide variety of uses. It is a component of many detergents, cosmetics, and enamel glazes.
It is also used to make buffer solutions in biochemistry, as a fire retardant, as an anti-fungal compound for fiberglass, as an insecticide, as a flux in metallurgy, and as a precursor for other boron compounds.
The term borax is used for a number of closely related minerals or chemical compounds that differ in their crystal water content, but usually refers to the decahydrate. Commercially sold borax is usually partially dehydrated.
# Name
The origin of the name is traceable to the Medieval Latin borat, which comes from the Arabic buraq, which comes from either the Persian burah or the Middle Persian burak.
# Uses
## Buffer
Sodium borate is used in biochemical and chemical laboratories to make SB buffers, e.g. for gel electrophoresis of DNA. It has a lower conductivity, produces sharper bands, and can be run at higher speeds than can gels made from TBE buffer or TAE buffer (5–35 V/cm as compared to 5–10 V/cm). At a given voltage, the heat generation and thus the gel temperature is much lower than with TBE or TAE buffers, therefore the voltage can be increased to speed up electrophoresis so that a gel run takes only a fraction of the usual time. Downstream applications, such as isolation of DNA from a gel slice or southern blot analysis, work as expected with sodium borate gels. Borate buffers (usually at pH 8) are also used as preferential equilibration solution in DMP-based crosslinking reactions.
Lithium borate is similar to sodium borate and has all of its advantages, but permits use of even higher voltages due to the lower conductivity of lithium ions as compared to sodium ions. However, lithium borate is much more expensive.
## Flux
A mixture of borax and ammonium chloride is used as a flux when welding iron and steel. It lowers the melting point of the unwanted iron oxide (scale), allowing it to run off. Borax is also used mixed with water as a flux when soldering jewelry metals such as gold or silver. It allows the molten solder to flow evenly over the joint in question. Borax is also a good flux for 'pre-tinning' tungsten with zinc - making the tungsten soft-solderable.
## Putty
When a borax-water solution is mixed with P.V.A glue it will harden forming a putty.
## Food additive
Borax is used as a food additive in some countries with the E number E285, but is banned in the United States. Its use is similar to common table salt, and it appears in French and Iranian caviar.
## Other uses
- Component of detergents
- Ingredient in enamel glazes
- Component of glass, pottery, and ceramics
- Fire retardant
- Anti-fungal compound for fibreglass and cellulose insulation
- Insecticide to kill ants and fleas
- Precursor for sodium perborate monohydrate that is used in detergents, as well as for boric acid and other borates
- Treatment for thrush in horses' hooves
- Used to make indelible ink for dip pens by dissolving shellac into heated borax
- Curing agent for snake skins
# Natural sources
Borax occurs naturally in evaporite deposits produced by the repeated evaporation of seasonal lakes (see playa). The most commercially important deposits are found in Turkey and near Boron, California and other locations in the Southwestern United States, the Atacama desert in Chile, and in Tibet. Borax can also be produced synthetically from other boron compounds.
# Toxicity
Boric acid, sodium borate, and sodium perborate are estimated to have a lethal dose (LD50) from 5 to 20 grams in humans. The estimated lethal dose (ingested) for adults is 15-20 grams; less than 5 grams can kill a child or pet. These substances are toxic to all cells, and have a slow excretion rate through the kidneys. Kidney toxicity is the greatest, with liver fatty degeneration, cerebral edema, and gastroenteritis. A reassessment of boric acid/borax by the United States Environmental Protection Agency Office of Pesticide Programs found potential developmental toxicity (especially effects on the testes). Boric acid solutions used as an eye wash or on abraded skin are known to be especially toxic to infants, especially after repeated use because of its slow elimination rate.
# Chemistry
The term borax is often used for a number of closely related minerals or chemical compounds that differ in their crystal water content:
- Anhydrous borax (Na2B4O7)
- Borax pentahydrate (Na2B4O7·5H2O)
- Borax decahydrate (Na2B4O7·10H2O)
Borax is generally described as Na2B4O7·10H2O. However, it is better formulated as Na2·8H2O, since borax contains the 2− ion. In this structure, there are two four-coordinate boron atoms (two BO4 tetrahedra) and two three-coordinate boron atoms (two BO3 triangles).
Borax is also easily converted to boric acid and other borates, which have many applications. If left exposed to dry air, it slowly loses its water of hydration and becomes the white and chalky mineral tincalconite (Na2B4O7·5H2O).
When borax is added to a flame, it produces a bright orange color. This property has been tried in amateur fireworks, but borax in this use is not popular because its waters of hydration inhibit combustion of compositions and make it an inferior source of the sodium which is responsible for most of its flame color, and which overwhelms the green contributed to the flame by boron.
However, commercially available borax can be mixed with flammables such as methanol to give the characteristic green flame of boron when ignited, which then slowly gives way to the characteristic yellow-orange flame of the sodium. | Borax
Template:Chembox new
Borax (from Persian burah), also known as sodium borate, sodium tetraborate, or disodium tetraborate, is an important boron compound, a mineral, and a salt of boric acid. It is usually a white powder consisting of soft colorless crystals that dissolve easily in water.
Borax has a wide variety of uses. It is a component of many detergents, cosmetics, and enamel glazes.
It is also used to make buffer solutions in biochemistry, as a fire retardant, as an anti-fungal compound for fiberglass, as an insecticide, as a flux in metallurgy, and as a precursor for other boron compounds.
The term borax is used for a number of closely related minerals or chemical compounds that differ in their crystal water content, but usually refers to the decahydrate. Commercially sold borax is usually partially dehydrated.
# Name
The origin of the name is traceable to the Medieval Latin borat, which comes from the Arabic buraq, which comes from either the Persian burah or the Middle Persian burak.[1][2]
# Uses
## Buffer
Sodium borate is used in biochemical and chemical laboratories to make SB buffers, e.g. for gel electrophoresis of DNA. It has a lower conductivity, produces sharper bands, and can be run at higher speeds than can gels made from TBE buffer or TAE buffer (5–35 V/cm as compared to 5–10 V/cm). At a given voltage, the heat generation and thus the gel temperature is much lower than with TBE or TAE buffers, therefore the voltage can be increased to speed up electrophoresis so that a gel run takes only a fraction of the usual time. Downstream applications, such as isolation of DNA from a gel slice or southern blot analysis, work as expected with sodium borate gels. Borate buffers (usually at pH 8) are also used as preferential equilibration solution in DMP-based crosslinking reactions.
Lithium borate is similar to sodium borate and has all of its advantages, but permits use of even higher voltages due to the lower conductivity of lithium ions as compared to sodium ions.[3] However, lithium borate is much more expensive.
## Flux
A mixture of borax and ammonium chloride is used as a flux when welding iron and steel. It lowers the melting point of the unwanted iron oxide (scale), allowing it to run off. Borax is also used mixed with water as a flux when soldering jewelry metals such as gold or silver. It allows the molten solder to flow evenly over the joint in question. Borax is also a good flux for 'pre-tinning' tungsten with zinc - making the tungsten soft-solderable.[4]
## Putty
When a borax-water solution is mixed with P.V.A glue it will harden forming a putty.
## Food additive
Borax is used as a food additive in some countries with the E number E285, but is banned in the United States. Its use is similar to common table salt, and it appears in French and Iranian caviar.
## Other uses
- Component of detergents
- Ingredient in enamel glazes
- Component of glass, pottery, and ceramics
- Fire retardant
- Anti-fungal compound for fibreglass and cellulose insulation
- Insecticide to kill ants and fleas
- Precursor for sodium perborate monohydrate that is used in detergents, as well as for boric acid and other borates
- Treatment for thrush in horses' hooves
- Used to make indelible ink for dip pens by dissolving shellac into heated borax
- Curing agent for snake skins
# Natural sources
Borax occurs naturally in evaporite deposits produced by the repeated evaporation of seasonal lakes (see playa). The most commercially important deposits are found in Turkey and near Boron, California and other locations in the Southwestern United States, the Atacama desert in Chile, and in Tibet. Borax can also be produced synthetically from other boron compounds.
# Toxicity
Boric acid, sodium borate, and sodium perborate are estimated to have a lethal dose (LD50) from 5 to 20 grams in humans[verification needed][5]. The estimated lethal dose (ingested) for adults is 15-20 grams; less than 5 grams can kill a child or pet. These substances are toxic to all cells, and have a slow excretion rate through the kidneys. Kidney toxicity is the greatest, with liver fatty degeneration, cerebral edema, and gastroenteritis. A reassessment of boric acid/borax by the United States Environmental Protection Agency Office of Pesticide Programs found potential developmental toxicity (especially effects on the testes).[6] Boric acid solutions used as an eye wash or on abraded skin are known to be especially toxic to infants, especially after repeated use because of its slow elimination rate.[7]
# Chemistry
The term borax is often used for a number of closely related minerals or chemical compounds that differ in their crystal water content:
- Anhydrous borax (Na2B4O7)
- Borax pentahydrate (Na2B4O7·5H2O)
- Borax decahydrate (Na2B4O7·10H2O)
Borax is generally described as Na2B4O7·10H2O. However, it is better formulated as Na2[B4O5(OH)4]·8H2O, since borax contains the [B4O5(OH)4]2− ion. In this structure, there are two four-coordinate boron atoms (two BO4 tetrahedra) and two three-coordinate boron atoms (two BO3 triangles).
Borax is also easily converted to boric acid and other borates, which have many applications. If left exposed to dry air, it slowly loses its water of hydration and becomes the white and chalky mineral tincalconite (Na2B4O7·5H2O).
When borax is added to a flame, it produces a bright orange color. This property has been tried in amateur fireworks, but borax in this use is not popular because its waters of hydration inhibit combustion of compositions and make it an inferior source of the sodium which is responsible for most of its flame color, and which overwhelms the green contributed to the flame by boron.
However, commercially available borax can be mixed with flammables such as methanol to give the characteristic green flame of boron when ignited, which then slowly gives way to the characteristic yellow-orange flame of the sodium. | https://www.wikidoc.org/index.php/Borax | |
73e22e250099a136fae2051d45814b2812d7983d | wikidoc | Boron | Boron
Boron (Template:PronEng) is a chemical element with atomic number 5 and the chemical symbol B. Boron is a trivalent nonmetallic element which occurs abundantly in the evaporite ores borax and ulexite. Boron is never found as a free element in nature.
Several allotropes of boron exist; amorphous boron is a brown powder, though crystalline boron is black, hard (9.3 on Mohs' scale), and a weak conductor at room temperature.
Elemental boron is used as a dopant in the semiconductor industry, while boron compounds play important roles as light structural materials, nontoxic insecticides and preservatives, and reagents for chemical synthesis.
Boron is an essential plant nutrient, although soil concentrations of > 1.0 ppm can cause marginal and tip necrosis in leaves as well as poor overall growth performance. Levels as low as 0.8 ppm can cause these same symptoms to appear in plants particularly sensitive to boron in the soil. Nearly all plants, even those somewhat tolerant of boron in the soil, will show at least some symptoms of boron toxicity when boron in the soil is greater than 1.8 ppm. When boron in the soil exceeds 2.0 ppm, few plants will perform well. Plants sensitive to boron in the soil may not survive. When boron levels in plant tissue exceed 200 ppm symptoms of boron toxicity are likely to appear. As an ultratrace element, boron is necessary for the optimal health of animals, though its physiological role in animals is poorly understood.
# Characteristics
Brown amorphous boron is a product of certain chemical reactions. It contains boron atoms randomly bonded to each other without long range order.
Crystalline boron, a very hard black material with a high melting point, exists in many polymorphs. Two rhombohedral forms, α-boron and β-boron containing 12 and 106.7 atoms in the rhombohedral unit cell respectively, and 50-atom tetragonal boron are the three most characterised crystalline forms.
Optical characteristics of crystalline/elemental boron include the transmittance of infrared light. At standard temperatures, elemental boron is a poor electrical conductor, but is a good electrical conductor at high temperatures.
Chemically boron is electron-deficient, possessing a vacant p-orbital. It is an electrophile. Compounds of boron often behave as Lewis acids, readily bonding with electron-rich substances to compensate for boron's electron deficiency. The reactions of boron are dominated by such requirement for electrons. Also, boron is the least electronegative non-metal, meaning that it is usually oxidized (loses electrons) in reactions.
Boron is also similar to carbon with its capability to form stable covalently bonded molecular networks. Boron is also used for heat resistant alloys. Boron forms a polyatomic B(II), such as B2F4.
# Applications
- In automobiles: it is proposed that by reacting water with elemental boron, hydrogen could be produced to be burnt in an internal combustion engine or fed to a fuel cell to generate electricity.
## 10B and 11B NMR spectroscopy
Both 10B (18.8 percent) and 11B (81.2 percent) possess nuclear spin; that of boron-10 has a value of 3 and that of boron-11, 3/2. These isotopes are, therefore, of use in nuclear magnetic resonance spectroscopy; and spectrometers specially adapted to detecting the boron-11 nucleus are available commercially. The boron-10 and boron-11 nuclei also cause splitting in the resonances of attached nuclei.
### B-10 depleted boron
The 10B isotope is good at capturing thermal neutrons from cosmic radiation. It then undergoes fission - producing a gamma ray, an alpha particle, and a lithium ion. When this happens inside of an integrated circuit, the fission products may then dump charge into nearby chip structures, causing data loss (bit flipping, or single event upset). In critical semiconductor designs, depleted boron—consisting almost entirely of 11B—is used to avoid this effect, as one of radiation hardening measures. 11B is a by-product of the nuclear industry. 11boron is also a candidate as a fuel for aneutronic fusion.
### B-10 enriched boron
The 10B isotope is good at capturing thermal neutrons, and this quality has been used in both radiation shielding and in boron neutron capture therapy where a tumor is treated with a compound containing 10B is attached to a muscle, and the patient treated with a relatively low dose of thermal neutrons which go on to cause energetic and short range alpha radiation in the tissue treated with the boron isotope.
In nuclear reactors, 10B is used for reactivity control and in emergency shutdown systems. It can serve either function in the form of borosilicate rods or as boric acid. In pressurized water reactors, boric acid is added to the reactor coolant when the plant is shut down for refueling. It is then slowly filtered out over many months as fissile material is used up and the fuel becomes less reactive.
In future manned interplanetary spacecraft, 10B has a theoretical role as structural material (as boron fibers or BN nanotube material) which also would serve a special role in the radiation shield. One of the difficulties in dealing with cosmic rays which are mostly high energy protons, is that some secondary radiation from interaction of cosmic rays and spacecraft structural materials, is in the form of high energy spallation neutrons. Such neutrons can be moderated by materials high in light elements such as structural polyethylene, but the moderated neutrons continue to be a radiation hazard unless actively absorbed in a way which dumps the absorption energy in the shielding, far away from biological systems. Among light elements that absorb thermal neutrons, 6Li and 10B appear as potential spacecraft structural materials able to do double duty in this regard.
## Market trend
Estimated global consumption of boron rose to a record 1.8 million tonnes of B2O3 in 2005 following a period of strong growth in demand from Asia, Europe and North America. Boron mining and refining capacities are considered to be adequate to meet expected levels of growth through the next decade.
The form in which boron is consumed has changed in recent years. The use of beneficiated ores like colemanite has declined following concerns over arsenic content. Consumers have moved towards the use of refined borates or boric acid that have a lower pollutant content.
Increasing demand for boric acid has led a number of producers to invest in additional capacity. Eti Mine opened a new 100,000 tonnes per year capacity boric acid plant at Emet in 2003. Rio Tinto increased the capacity of its Boron plant from 260,000 tonnes per year in 2003 to 310,000 tonnes per year by May 2005, with plans to grow this to 366,000 tonnes per year in 2006.
Chinese boron producers have been unable to meet rapidly growing demand for high quality borates. This has led to imports of disodium tetraborate growing by a hundredfold between 2000 and 2005 and boric acid imports increasing by 28% per year over the same period.
The rise in global demand has been driven by high rates of growth in fiberglass and borosilicate production. A rapid increase in the manufacture of reinforcement-grade fiberglass in Asia with a consequent increase in demand for borates has offset the development of boron-free reinforcement-grade fiberglass in Europe and the USA. The recent rises in energy prices can be expected to lead to greater use of insulation-grade fiberglass, with consequent growth in the use of boron.
Roskill Consulting Group forecasts that world demand for boron will grow by 3.4% per year to reach 21 million tonnes by 2010. The highest growth in demand is expected to be in Asia where demand could rise by an average 5.7% per year.
# Boron compounds
## The most economically important compounds of boron
- Sodium tetraborate pentahydrate (Na2B4O7 · 5H2O), which is used in large amounts in making insulating fiberglass and sodium perborate bleach,
- Orthoboric acid (H3BO3) or boric acid, used in the production of textile fiberglass and flat panel displays or eye drops, among many uses, and
- Sodium tetraborate decahydrate (Na2B4O7 · 10H2O) or borax, used in the production of adhesives, in anti-corrosion systems and many other uses.
- Boron nitride is a material in which the extra electron of nitrogen (with respect to carbon) in some ways compensates for boron's deficiency of an electron.
- Boron reacts with ammonia at high temperatures to give a compound called borazole (B3N3H6), also known as inorganic benzene.
## Of the several hundred uses of boron compounds, especially notable uses
- Boron is an essential plant micronutrient.
- Because of its distinctive green flame, amorphous boron is used in pyrotechnic flares.
- Boric acid is an important compound used in textile products.
- Boric acid is also traditionally used as an insecticide, notably against ants, fleas, and cockroaches.
- Borax is sometimes found in laundry detergent.
- Boron filaments are high-strength, lightweight materials that are chiefly used for advanced aerospace structures as a component of composite materials, as well as limited production consumer and sporting goods such as golf clubs and fishing rods.
- Boron is used as a melting point depressant in nickel-chromium braze alloys.
- Boron slurry is used as an energetic material with very high energy density like rocket fuels and jet engines.
- Boron compounds show promise in treating arthritis.
## Hardest boron compound
The hardest Boron compound is created synthetically. Rhenium diboride (ReB2) can actually scratch diamond, giving it a higher than 10 rank in the Mohs scale of mineral hardness and making it one of the three hardest substances known to man - the other two being ultrahard fullerite and aggregated diamond nanorods.
# History
Compounds of boron (Arabic Buraq from Persian Burah from Turkish Bor) have been known of for thousands of years. In early Egypt, mummification depended upon an ore known as natron, which contained borates as well as some other common salts. Borax glazes were used in China from 300 AD, and boron compounds were used in glassmaking in ancient Rome.
The element was not isolated until 1808 by Sir Humphry Davy, Joseph Louis Gay-Lussac, and Louis Jacques Thénard, to about 50 percent purity, by the reduction of boric acid with sodium or magnesium. These men did not recognize the substance as an element. It was Jöns Jakob Berzelius in 1824 who identified boron as an element. The first pure boron was produced by the American chemist W. Weintraub in 1909, although this is disputed by some researchers.
It is thought that boron plays several biochemical roles in animals, including humans.
# Occurrence
Turkey and the United States are the world's largest producers of boron. Turkey has almost 63% of the world’s boron potential and boron reserves. Boron does not appear in nature in elemental form but is found combined in borax, boric acid, colemanite, kernite, ulexite and borates. Boric acid is sometimes found in volcanic spring waters. Ulexite is a borate mineral that naturally has properties of fiber optics.
Economically important sources are from the ore rasorite (kernite) and tincal (borax ore) which are both found in the Mojave Desert of California, with borax being the most important source there. The largest borax deposits are found in Central and Western Turkey including the provinces of Eskişehir, Kütahya and Balıkesir.
Even a boron-containing natural antibiotic, boromycin, isolated from streptomyces, is known.
Pure elemental boron is not easy to prepare. The earliest methods used involve reduction of boric oxide with metals such as magnesium or aluminium. However the product is almost always contaminated with metal borides. (The reaction is quite spectacular though.) Pure boron can be prepared by reducing volatile boron halogenides with hydrogen at high temperatures. The highly pure boron, for the use in semiconductor industry, is produced by the decomposition of diborane at high temperatures and then further purified with the Czochralski process.
## Food
Boron occurs in all foods produced from plants. Since 1989 its nutritional value has been argued. The U.S. Department of agriculture conducted an experiment in which postmenopausal women took 3 mg of boron a day. The results showed that boron can reduce excretion of calcium by 44%, and activate estrogen and vitamin D.
The US National Institute of Health quotes this source:
See also: Borate minerals.
## Analytical quantification
For determination of boron content in food or materials the colorimetric curcumin method is used. Boron has to be transferred to boric acid or borates and on reaction with curcumin in acidic solution a red colored boron-chelate complex, rosocyanine, is formed.
# Isotopes
Boron has two naturally-occurring and stable isotopes, 11B (80.1%) and 10B (19.9%). The mass difference results in a wide range of δ11B values in natural waters, ranging from -16 to +59. There are 13 known isotopes of boron, the shortest-lived isotope is 7B which decays through proton emission and alpha decay. It has a half-life of 3.26500x10-22 s. Isotopic fractionation of boron is controlled by the exchange reactions of the boron species B(OH)3 and B(OH)4. Boron isotopes are also fractionated during mineral crystallization, during H2O phase changes in hydrothermal systems, and during hydrothermal alteration of rock. The latter effect species preferential removal of the 10B(OH)4 ion onto clays results in solutions enriched in 11B(OH)3 may be responsible for the large 11B enrichment in seawater relative to both oceanic crust and continental crust; this difference may act as an isotopic signature.
The exotic 17B exhibits a Nuclear halo.
# Precautions
Elemental boron is nontoxic and common boron compounds such as borates and boric acid have low toxicity (approximately similar to table salt with the lethal dose being 2 to 3 grams per kg) and therefore do not require special precautions while handling. Some of the more exotic boron hydrogen compounds, however, are toxic as well as highly flammable and do require special handling care. | Boron
Template:Elementbox
Boron (Template:PronEng) is a chemical element with atomic number 5 and the chemical symbol B. Boron is a trivalent nonmetallic element which occurs abundantly in the evaporite ores borax and ulexite. Boron is never found as a free element in nature.
Several allotropes of boron exist; amorphous boron is a brown powder, though crystalline boron is black, hard (9.3 on Mohs' scale), and a weak conductor at room temperature.
Elemental boron is used as a dopant in the semiconductor industry, while boron compounds play important roles as light structural materials, nontoxic insecticides and preservatives, and reagents for chemical synthesis.
Boron is an essential plant nutrient, although soil concentrations of > 1.0 ppm can cause marginal and tip necrosis in leaves as well as poor overall growth performance. Levels as low as 0.8 ppm can cause these same symptoms to appear in plants particularly sensitive to boron in the soil. Nearly all plants, even those somewhat tolerant of boron in the soil, will show at least some symptoms of boron toxicity when boron in the soil is greater than 1.8 ppm. When boron in the soil exceeds 2.0 ppm, few plants will perform well. Plants sensitive to boron in the soil may not survive. When boron levels in plant tissue exceed 200 ppm symptoms of boron toxicity are likely to appear. As an ultratrace element, boron is necessary for the optimal health of animals, though its physiological role in animals is poorly understood.
# Characteristics
Brown amorphous boron is a product of certain chemical reactions. It contains boron atoms randomly bonded to each other without long range order.
Crystalline boron, a very hard black material with a high melting point, exists in many polymorphs. Two rhombohedral forms, α-boron and β-boron containing 12 and 106.7 atoms in the rhombohedral unit cell respectively, and 50-atom tetragonal boron are the three most characterised crystalline forms.
Optical characteristics of crystalline/elemental boron include the transmittance of infrared light. At standard temperatures, elemental boron is a poor electrical conductor, but is a good electrical conductor at high temperatures.
Chemically boron is electron-deficient, possessing a vacant p-orbital. It is an electrophile. Compounds of boron often behave as Lewis acids, readily bonding with electron-rich substances to compensate for boron's electron deficiency. The reactions of boron are dominated by such requirement for electrons. Also, boron is the least electronegative non-metal, meaning that it is usually oxidized (loses electrons) in reactions.
Boron is also similar to carbon with its capability to form stable covalently bonded molecular networks. Boron is also used for heat resistant alloys. Boron forms a polyatomic B(II), such as B2F4.[1]
# Applications
- In automobiles: it is proposed that by reacting water with elemental boron, hydrogen could be produced to be burnt in an internal combustion engine or fed to a fuel cell to generate electricity.[2]
## 10B and 11B NMR spectroscopy
Both 10B (18.8 percent) and 11B (81.2 percent) possess nuclear spin; that of boron-10 has a value of 3 and that of boron-11, 3/2. These isotopes are, therefore, of use in nuclear magnetic resonance spectroscopy; and spectrometers specially adapted to detecting the boron-11 nucleus are available commercially. The boron-10 and boron-11 nuclei also cause splitting in the resonances of attached nuclei.
### B-10 depleted boron
The 10B isotope is good at capturing thermal neutrons from cosmic radiation. It then undergoes fission - producing a gamma ray, an alpha particle, and a lithium ion. When this happens inside of an integrated circuit, the fission products may then dump charge into nearby chip structures, causing data loss (bit flipping, or single event upset). In critical semiconductor designs, depleted boron—consisting almost entirely of 11B—is used to avoid this effect, as one of radiation hardening measures. 11B is a by-product of the nuclear industry. 11boron is also a candidate as a fuel for aneutronic fusion.
### B-10 enriched boron
The 10B isotope is good at capturing thermal neutrons, and this quality has been used in both radiation shielding and in boron neutron capture therapy where a tumor is treated with a compound containing 10B is attached to a muscle, and the patient treated with a relatively low dose of thermal neutrons which go on to cause energetic and short range alpha radiation in the tissue treated with the boron isotope.
In nuclear reactors, 10B is used for reactivity control and in emergency shutdown systems. It can serve either function in the form of borosilicate rods or as boric acid. In pressurized water reactors, boric acid is added to the reactor coolant when the plant is shut down for refueling. It is then slowly filtered out over many months as fissile material is used up and the fuel becomes less reactive.
In future manned interplanetary spacecraft, 10B has a theoretical role as structural material (as boron fibers or BN nanotube material) which also would serve a special role in the radiation shield. One of the difficulties in dealing with cosmic rays which are mostly high energy protons, is that some secondary radiation from interaction of cosmic rays and spacecraft structural materials, is in the form of high energy spallation neutrons. Such neutrons can be moderated by materials high in light elements such as structural polyethylene, but the moderated neutrons continue to be a radiation hazard unless actively absorbed in a way which dumps the absorption energy in the shielding, far away from biological systems. Among light elements that absorb thermal neutrons, 6Li and 10B appear as potential spacecraft structural materials able to do double duty in this regard.
## Market trend
Estimated global consumption of boron rose to a record 1.8 million tonnes of B2O3 in 2005 following a period of strong growth in demand from Asia, Europe and North America. Boron mining and refining capacities are considered to be adequate to meet expected levels of growth through the next decade.
The form in which boron is consumed has changed in recent years. The use of beneficiated ores like colemanite has declined following concerns over arsenic content. Consumers have moved towards the use of refined borates or boric acid that have a lower pollutant content.
Increasing demand for boric acid has led a number of producers to invest in additional capacity. Eti Mine opened a new 100,000 tonnes per year capacity boric acid plant at Emet in 2003. Rio Tinto increased the capacity of its Boron plant from 260,000 tonnes per year in 2003 to 310,000 tonnes per year by May 2005, with plans to grow this to 366,000 tonnes per year in 2006.
Chinese boron producers have been unable to meet rapidly growing demand for high quality borates. This has led to imports of disodium tetraborate growing by a hundredfold between 2000 and 2005 and boric acid imports increasing by 28% per year over the same period.
The rise in global demand has been driven by high rates of growth in fiberglass and borosilicate production. A rapid increase in the manufacture of reinforcement-grade fiberglass in Asia with a consequent increase in demand for borates has offset the development of boron-free reinforcement-grade fiberglass in Europe and the USA. The recent rises in energy prices can be expected to lead to greater use of insulation-grade fiberglass, with consequent growth in the use of boron.
Roskill Consulting Group forecasts that world demand for boron will grow by 3.4% per year to reach 21 million tonnes by 2010. The highest growth in demand is expected to be in Asia where demand could rise by an average 5.7% per year.[3]
# Boron compounds
Template:Seealso
## The most economically important compounds of boron
- Sodium tetraborate pentahydrate (Na2B4O7 · 5H2O), which is used in large amounts in making insulating fiberglass and sodium perborate bleach,
- Orthoboric acid (H3BO3) or boric acid, used in the production of textile fiberglass and flat panel displays or eye drops, among many uses, and
- Sodium tetraborate decahydrate (Na2B4O7 · 10H2O) or borax, used in the production of adhesives, in anti-corrosion systems and many other uses.
- Boron nitride is a material in which the extra electron of nitrogen (with respect to carbon) in some ways compensates for boron's deficiency of an electron.
- Boron reacts with ammonia at high temperatures to give a compound called borazole (B3N3H6), also known as inorganic benzene.
## Of the several hundred uses of boron compounds, especially notable uses
- Boron is an essential plant micronutrient.
- Because of its distinctive green flame, amorphous boron is used in pyrotechnic flares.
- Boric acid is an important compound used in textile products.
- Boric acid is also traditionally used as an insecticide, notably against ants, fleas, and cockroaches.
- Borax is sometimes found in laundry detergent.
- Boron filaments are high-strength, lightweight materials that are chiefly used for advanced aerospace structures as a component of composite materials, as well as limited production consumer and sporting goods such as golf clubs and fishing rods.
- Boron is used as a melting point depressant in nickel-chromium braze alloys.
- Boron slurry is used as an energetic material with very high energy density like rocket fuels and jet engines.
- Boron compounds show promise in treating arthritis.
## Hardest boron compound
The hardest Boron compound is created synthetically. Rhenium diboride (ReB2) can actually scratch diamond, giving it a higher than 10 rank in the Mohs scale of mineral hardness and making it one of the three hardest substances known to man - the other two being ultrahard fullerite and aggregated diamond nanorods.
# History
Compounds of boron (Arabic Buraq from Persian Burah from Turkish Bor) have been known of for thousands of years. In early Egypt, mummification depended upon an ore known as natron, which contained borates as well as some other common salts. Borax glazes were used in China from 300 AD, and boron compounds were used in glassmaking in ancient Rome.
The element was not isolated until 1808 by Sir Humphry Davy, Joseph Louis Gay-Lussac, and Louis Jacques Thénard, to about 50 percent purity, by the reduction of boric acid with sodium or magnesium. These men did not recognize the substance as an element. It was Jöns Jakob Berzelius in 1824 who identified boron as an element. The first pure boron was produced by the American chemist W. Weintraub in 1909, although this is disputed by some researchers.[4]
It is thought that boron plays several biochemical roles in animals, including humans.[5]
# Occurrence
Turkey and the United States are the world's largest producers of boron. Turkey has almost 63% of the world’s boron potential and boron reserves.[6] Boron does not appear in nature in elemental form but is found combined in borax, boric acid, colemanite, kernite, ulexite and borates. Boric acid is sometimes found in volcanic spring waters. Ulexite is a borate mineral that naturally has properties of fiber optics.
Economically important sources are from the ore rasorite (kernite) and tincal (borax ore) which are both found in the Mojave Desert of California, with borax being the most important source there. The largest borax deposits are found in Central and Western Turkey including the provinces of Eskişehir, Kütahya and Balıkesir.
Even a boron-containing natural antibiotic, boromycin, isolated from streptomyces, is known.[7][8]
Pure elemental boron is not easy to prepare. The earliest methods used involve reduction of boric oxide with metals such as magnesium or aluminium. However the product is almost always contaminated with metal borides. (The reaction is quite spectacular though.) Pure boron can be prepared by reducing volatile boron halogenides with hydrogen at high temperatures. The highly pure boron, for the use in semiconductor industry, is produced by the decomposition of diborane at high temperatures and then further purified with the Czochralski process.
## Food
Boron occurs in all foods produced from plants. Since 1989 its nutritional value has been argued. The U.S. Department of agriculture conducted an experiment in which postmenopausal women took 3 mg of boron a day. The results showed that boron can reduce excretion of calcium by 44%, and activate estrogen and vitamin D.
The US National Institute of Health quotes this source:
See also: Borate minerals.
## Analytical quantification
For determination of boron content in food or materials the colorimetric curcumin method is used. Boron has to be transferred to boric acid or borates and on reaction with curcumin in acidic solution a red colored boron-chelate complex, rosocyanine, is formed.
# Isotopes
Boron has two naturally-occurring and stable isotopes, 11B (80.1%) and 10B (19.9%). The mass difference results in a wide range of δ11B values in natural waters, ranging from -16 to +59. There are 13 known isotopes of boron, the shortest-lived isotope is 7B which decays through proton emission and alpha decay. It has a half-life of 3.26500x10-22 s. Isotopic fractionation of boron is controlled by the exchange reactions of the boron species B(OH)3 and B(OH)4. Boron isotopes are also fractionated during mineral crystallization, during H2O phase changes in hydrothermal systems, and during hydrothermal alteration of rock. The latter effect species preferential removal of the 10B(OH)4 ion onto clays results in solutions enriched in 11B(OH)3 may be responsible for the large 11B enrichment in seawater relative to both oceanic crust and continental crust; this difference may act as an isotopic signature.
The exotic 17B exhibits a Nuclear halo.
# Precautions
Elemental boron is nontoxic and common boron compounds such as borates and boric acid have low toxicity (approximately similar to table salt with the lethal dose being 2 to 3 grams per kg) and therefore do not require special precautions while handling. Some of the more exotic boron hydrogen compounds, however, are toxic as well as highly flammable and do require special handling care. | https://www.wikidoc.org/index.php/Boron | |
8b10465f48f279e095589a5b698206c3bdb46b72 | wikidoc | Boson | Boson
In particle physics, bosons are particles with an integer spin, as opposed to fermions which have half-integer spin. From a behaviour point of view, fermions are particles that obey the Fermi-Dirac statistics while bosons are particles that obey the Bose-Einstein statistics. They may be either elementary, like the photon, or composite, as mesons. All force carrier particles are bosons. They are named after Satyendra Nath Bose. In contrast to fermions, several bosons can occupy the same quantum state. Thus, bosons with the same energy can occupy the same place in space.
While most bosons are composite particles, four bosons (the gauge bosons) are elementary particles not known to be composed of other particles. The only boson in the Standard Model that is yet to be discovered experimentally is the Higgs boson.
# Basic properties
All elementary and composite particles in 3 dimensional space are either bosons or fermions, depending on their spin. Particles with half-integer spin are fermions; particles with integer spin are bosons. The spin-statistics theorem identifies the resulting quantum statistics that differentiate fermions and bosons. Bosons obey Bose–Einstein statistics. Fermions, on the other hand, cannot occupy the same quantum state as each other; they obey the Fermi-Dirac statistics and the Pauli exclusion principle. They "resist" being placed close to each other. So, fermions possess "rigidness" and thus sometimes are considered to be "particles of matter".
The properties of lasers and masers, superfluid helium-4 and Bose–Einstein condensates are all consequences of statistics of bosons. Another result is that the spectrum of a photon gas in thermal equilibrium is a Planck spectrum, one example of which is black-body radiation; another is the thermal radiation of the opaque early Universe seen today as microwave background radiation.
Interaction of virtual bosons with real fermions are called fundamental interactions, and these result in all forces we know. The bosons involved in these interactions are called gauge bosons. These include the W and Z bosons of the weak force, the gluons of the strong force, the photons of the electromagnetic force, and, in quantum gravity, the yet to be verified graviton of the gravitational force.
In large systems, the difference between bosonic and fermionic statistics is only apparent at large densities—when their wave functions overlap. At low densities, both types of statistics are well approximated by Maxwell-Boltzmann statistics, which is described by classical mechanics.
# Composite bosons
Particles composed of a number of other particles (such as protons, neutrons or nuclei) can be either fermions or bosons, depending on their total spin. Hence, many nuclei are bosons. For instance, consider 3He. It is made of 2 protons, a neutron and 2 electrons. Since the spins of these five fermions must add to a half integer, 3He is a fermion. On the other hand 4He, which is made of six fermions, is a boson. Likewise, the deuteron (2H+), which is composed of a proton and a neutron, is a boson, however the neutral deuterium atom, which also has an electron, is a fermion.
Composite bosons exhibit bosonic behavior only at distances large compared to their structure size. At a small distance they behave according to properties of their constituent particles. For example, despite the fact that an alpha particle is a boson, at high energy it interacts with another alpha particle not as a boson but as an ensemble of fermions.
# Examples of bosons
- Photons, which mediate the electromagnetic force
- W and Z bosons, which mediate the weak nuclear force
- Gluons, which mediate the strong nuclear force
- Higgs bosons
- Phonons
- Cooper pairs | Boson
In particle physics, bosons are particles with an integer spin, as opposed to fermions which have half-integer spin. From a behaviour point of view, fermions are particles that obey the Fermi-Dirac statistics while bosons are particles that obey the Bose-Einstein statistics. They may be either elementary, like the photon, or composite, as mesons. All force carrier particles are bosons. They are named after Satyendra Nath Bose. In contrast to fermions, several bosons can occupy the same quantum state. Thus, bosons with the same energy can occupy the same place in space.
While most bosons are composite particles, four bosons (the gauge bosons) are elementary particles not known to be composed of other particles. The only boson in the Standard Model that is yet to be discovered experimentally is the Higgs boson.[1]
# Basic properties
All elementary and composite particles in 3 dimensional space are either bosons or fermions, depending on their spin. Particles with half-integer spin are fermions; particles with integer spin are bosons. The spin-statistics theorem identifies the resulting quantum statistics that differentiate fermions and bosons. Bosons obey Bose–Einstein statistics. Fermions, on the other hand, cannot occupy the same quantum state as each other; they obey the Fermi-Dirac statistics and the Pauli exclusion principle. They "resist" being placed close to each other. So, fermions possess "rigidness" and thus sometimes are considered to be "particles of matter".
The properties of lasers and masers, superfluid helium-4 and Bose–Einstein condensates are all consequences of statistics of bosons. Another result is that the spectrum of a photon gas in thermal equilibrium is a Planck spectrum, one example of which is black-body radiation; another is the thermal radiation of the opaque early Universe seen today as microwave background radiation.
Interaction of virtual bosons with real fermions are called fundamental interactions, and these result in all forces we know. The bosons involved in these interactions are called gauge bosons. These include the W and Z bosons of the weak force, the gluons of the strong force, the photons of the electromagnetic force, and, in quantum gravity, the yet to be verified graviton of the gravitational force.
In large systems, the difference between bosonic and fermionic statistics is only apparent at large densities—when their wave functions overlap. At low densities, both types of statistics are well approximated by Maxwell-Boltzmann statistics, which is described by classical mechanics.
# Composite bosons
Particles composed of a number of other particles (such as protons, neutrons or nuclei) can be either fermions or bosons, depending on their total spin. Hence, many nuclei are bosons. For instance, consider 3He. It is made of 2 protons, a neutron and 2 electrons. Since the spins of these five fermions must add to a half integer, 3He is a fermion. On the other hand 4He, which is made of six fermions, is a boson. Likewise, the deuteron (2H+), which is composed of a proton and a neutron, is a boson, however the neutral deuterium atom, which also has an electron, is a fermion.
Composite bosons exhibit bosonic behavior only at distances large compared to their structure size. At a small distance they behave according to properties of their constituent particles. For example, despite the fact that an alpha particle is a boson, at high energy it interacts with another alpha particle not as a boson but as an ensemble of fermions.
# Examples of bosons
- Photons, which mediate the electromagnetic force
- W and Z bosons, which mediate the weak nuclear force
- Gluons, which mediate the strong nuclear force
- Higgs bosons
- Phonons
- Cooper pairs | https://www.wikidoc.org/index.php/Boson | |
06287bba796e88fb3817519c9d89bce2c127b0be | wikidoc | Brain | Brain
In animals, the brain is the control center of the central nervous system, responsible for behavior. The brain is located in the head, protected by the skull and close to the primary sensory apparatus of vision, hearing, equilibrioception (balance), sense of taste, and olfaction (smell). While all vertebrates have a brain, most invertebrates have either a centralized brain or collections of individual ganglia. Some animals such as cnidarians and echinoderms do not have a centralized brain, instead have a decentralized nervous system, while animals such as sponges lack both a brain and nervous system entirely. Brains can be extremely complex. For example, the human brain contains roughly 23 billion neurons, each linked to as many as 10,000 other neurons.
# Overview
The brain is the central information-processing organ of the body. It innervates the head through cranial nerves, and it communicates with the spinal cord, which innervates the body through spinal nerves. Nervous fibers transmitting signals from the brain are called efferent fibers. The fibers transmitting signals to the brain are called afferent fibers (or sensory fibers). Nerves can be afferent, efferent or mixed (i.e., containing both types of fibers).
The brain is the site of reason and intelligence, which include such components as cognition, perception, attention, memory and emotion. The brain is also responsible for control of posture and movements. It makes possible cognitive, motor and other forms of learning. The brain can perform a variety of functions automatically, without the need for conscious awareness, such as coordination of sensory systems (eg. sensory gating and multisensory integration), walking, and homeostatic body functions such as blood pressure, fluid balance, and body temperature.
The Cerebellum controls balance and movement. Without it, movements would not be coordinated.
Many functions are controlled by coordinated activity of the brain and spinal cord. Moreover, some behaviors such as simple reflexes and basic locomotion, can be executed under spinal cord control alone.
The brain undergoes transitions from wakefulness to sleep (and subtypes of these states). These state transitions are crucially important for proper brain functioning. (For example, it is believed that sleep is important for knowledge consolidation, as the neurons appear to organize the day's stimuli during deep sleep by randomly firing off the most recently used neuron pathways; additionally, without sleep, normal subjects are observed to develop symptoms resembling mental illness, even auditory hallucinations). Every brain state is associated with characteristic brain waves.
Neurons are electrically active brain cells that process information, whereas Glial cells perform supporting function. In addition to being electrically active, neurons constantly synthesize neurotransmitters. Neurons modify their properties (guided by gene expression) under the influence of their input signals. This plasticity underlies learning and adaptation. It is notable that some unused neuron pathways (constructions which have become physically isolated from other cells) may continue to exist long after the memory is absent from consciousness, possibly developing the subconscious.
The study of the brain is known as neuroscience, a field of biology aimed at understanding the functions of the brain at every level, from the molecular up to the psychological. There is also a branch of psychology that deals with the anatomy and physiology of the brain, known as biological psychology. This field of study focuses on each individual part of the brain and how it affects behavior.
# History
Early views on the function of the brain regarded it as little more than cranial stuffing. In Ancient Egypt, from the late Middle Kingdom onwards, in preparation for mummification, the brain was regularly removed, for it was the heart that was assumed to be the seat of intelligence. According to Herodotus, during the first step of mummification, "The most perfect practice is to extract as much of the brain as possible with an iron hook, and what the hook cannot reach is mixed with drugs." Over the next five-thousand years, this view came to be reversed; the brain is now known to be seat of intelligence, although idiomatic variations of the former remain, as in memorizing something "by heart".
The first thoughts on the field of psychology came from ancient philosophers, such as Aristotle. As thinkers became more in tune with biomedical research over time, as was the case with medieval psychologists such as Alhazen and Avicenna for example, the concepts of experimental psychology and clinical psychology began emerging. From that point, different branches of psychology emerged with different individuals creating new ideas, with modern psychologists such as Freud and Jung contributing to the field.
# Mind and brain
The distinction between the mind and the brain is fundamental in philosophy of mind. The mind-body problem is one of the central problems in the history of philosophy. The brain is the physical and biological matter contained within the skull, responsible for electrochemical neuronal processes. The mind, in contrast, consists in mental attributes, such as beliefs, desires, perceptions, and so on. There are scientifically demonstrable correlations between mental events and neuronal events; the philosophical question is whether these phenomena are identical or are related in some other way.
The philosophical positions on the mind-body problem fall into two main categories. The first category is dualism, according to which the mind exists independently of the brain. Dualist theories are further divided into substance dualism and property dualism. Descartes is perhaps the most prominent substance dualist, while property dualism is more popular among contemporary dualists like David Chalmers. The second category is materialism, according to which mental phenomena are identical to neuronal phenomena. A third category of view, idealism, claims that only mental substances and phenomena exist. This view, most prominently held by 18th century English philosopher George Berkeley, has few contemporary adherents.
Both dualism and materialism face serious philosophical challenges. Dualism requires that we admit non-physical substances or properties into our ontology, a move that places dualism in apparent conflict with the scientific world view. Materialism, on the other hand, must provide an explanation of how two seemingly different kinds of phenomena - the mental and the physical - could be identical. This challenge can be seen by noting that mental phenomena have certain characteristics - particularly intentionality and phenomenal character - that physical phenomena do not, and seemingly could not, have.
# Comparative anatomy
Three groups of animals have notably complex brains: the arthropods (insects, crustaceans, arachnids, and others), the cephalopods (octopuses, squids, and similar mollusks), and the craniates (vertebrates and hagfish). The brain of arthropods and cephalopods arises from twin parallel nerve cords that extend through the body of the animal. Arthropods have a central brain with three divisions and large optical lobes behind each eye for visual processing.
The brain of craniates develops from the anterior section of a single dorsal nerve cord, which later becomes the spinal cord. In craniates, the brain is protected by the bones of the skull.
Mammals have a six-layered neocortex (or homotypic cortex, neopallium), in addition to having some parts of the brain that are allocortex. In mammals, increasing convolutions of the brain are characteristic of animals with more advanced brains. These convolutions provide a larger surface area for a greater number of neurons while keeping the volume of the brain compact enough to fit inside the skull. The folding allows more grey matter to fit into a smaller volume, similar to a really long slinky being able to fit into a tiny box when completely pushed together. The folds are called gyri, while the spaces between the folds are called sulci.
In birds, the part of the brain that functionally corresponds to the neocortex is called nidopallium and derives from a different part of the brain. Some birds (like corvids and parrots) have intelligence equal to great apes, but even in these, the brain region that forms the mammalian neocortex is in fact almost entirely absent.
Although the general histology of the brain is similar from person to person, the structural anatomy can differ. Apart from the gross embryological divisions of the brain, the location of specific gyri and sulci, primary sensory regions, and other structures differs between species.
## Mammals and other vertebrates
The telencephalon (cerebrum) is the largest region of the mammalian brain. This is the structure that is most easily visible in brain specimens, and is what most people associate with the "brain". In humans and several other animals, the fissures (sulci) and convolutions (gyri) give the brain a wrinkled appearance. In non-mammalian vertebrates with no cerebrum, the metencephalon is the highest center in the brain. Because humans walk upright, there is a flexure, or bend, in the brain between the brain stem and the cerebrum. Other vertebrates do not have this flexure. Generally, comparing the locations of certain brain structures between humans and other vertebrates often reveals a number of differences.
Behind (or in humans, below) the cerebrum is the cerebellum. The cerebellum is known to be involved in the control of movement, and is connected by thick white matter fibers (cerebellar peduncles) to the pons. The cerebrum has two cerebral hemispheres. The cerebellum also has hemispheres. The telencephalic hemispheres are connected by the corpus callosum, another large white matter tract. An outgrowth of the telencephalon called the olfactory bulb is a major structure in many animals, but in humans and other primates it is relatively small.
Vertebrate nervous systems are distinguished by bilaterally symmetrical encephalization. Encephalization refers to the tendency for more complex organisms to gain larger brains through evolutionary time. Larger vertebrates develop a complex, layered and interconnected neuronal circuitry. In modern species most closely related to the first vertebrates, brains are covered with gray matter that has a three-layer structure (allocortex). Their brains also contain deep brain nuclei and fiber tracts forming the white matter. Most regions of the human cerebral cortex have six layers of neurons (neocortex).
### Vertebrate brain regions
(See related article at List of regions in the human brain)
According to the hierarchy based on embryonic and evolutionary development, chordate brains are composed of the three regions that later develop into five total divisions:
- Rhombencephalon (hindbrain)
Myelencephalon
Metencephalon
- Myelencephalon
- Metencephalon
- Mesencephalon (midbrain)
- Prosencephalon (forebrain)
Diencephalon
Telencephalon
- Diencephalon
- Telencephalon
The brain can also be classified according to function, including divisions such as:
- Limbic system
- Sensory systems
Visual system
Olfactory system
Gustatory system
Auditory system
Somatosensory system
- Visual system
- Olfactory system
- Gustatory system
- Auditory system
- Somatosensory system
- Motor system
- Associative areas
In recent years it was realized that certain birds have developed high intelligence entirely convergently from mammals such as humans. Hence, the functional areas of the avian brain have been redefined by the Avian Brain Nomenclature Consortium.
### Humans
The structure of the human brain differs from that of other animals in several important ways. These differences allow for many abilities over and above those of other animals, such as advanced cognitive skills. Human encephalization is especially pronounced in the neocortex, the most complex part of the cerebral cortex. The proportion of the human brain that is devoted to the neocortex—especially to the prefrontal cortex—is larger than in all other mammals (indeed larger than in all animals, although only in mammals has the neocortex evolved to fulfill this kind of function).
Humans have unique neural capacities, but much of their brain structure is similar to that of other mammals. Basic systems that alert the nervous system to stimulus, that sense events in the environment, and monitor the condition of the body are similar to those of even non-mammalian vertebrates. The neural circuitry underlying human consciousness includes both the advanced neocortex and prototypical structures of the brainstem. The human brain also has a massive number of synaptic connections allowing for a great deal of parallel processing.
# Neurobiology
The brain is composed of two broad classes of cells, neurons and glia, both of which contain several different cell types which perform different functions. Interconnected neurons form neural networks (or neural ensembles). These networks are similar to man-made electrical circuits in that they contain circuit elements (neurons) connected by biological wires (nerve fibers). These do not form simple one-to-one electrical circuits like many man-made circuits, however. Typically neurons connect to at least a thousand other neurons. These highly specialized circuits make up systems which are the basis of perception, different types of action, and higher cognitive function.
## Structure
Neurons are the cells that generate action potentials and convey information to other cells; these constitute the essential class of brain cells.
In addition to neurons, the brain contains glial cells in a roughly 10:1 proportion to neurons. Glial cells ("glia" is Greek for “glue”) form a support system for neurons. They create the insulating myelin, provide structure to the neuronal network, manage waste, and clean up neurotransmitters. Most types of glia in the brain are present in the entire nervous system. Exceptions include the oligodendrocytes which myelinate neural axons (a role performed by Schwann cells in the peripheral nervous system). The myelin in the oligodendrocytes insulates the axons of some neurons. White matter in the brain is myelinated neurons, while grey matter contains mostly cell soma, dendrites, and unmyelinated portions of axons and glia. The space between neurons is filled with dendrites as well as unmyelinated segments of axons; this area is referred to as the neuropil.
In mammals, the brain is surrounded by connective tissues called the meninges, a system of membranes that separate the skull from the brain. This three-layered covering is composed of (from the outside in) the dura mater, arachnoid mater, and pia mater. The arachnoid and pia are physically connected and thus often considered as a single layer, the pia-arachnoid. Below the arachnoid is the subarachnoid space which contains cerebrospinal fluid, a substance that protects the nervous system. Blood vessels enter the central nervous system through the perivascular space above the pia mater. The cells in the blood vessel walls are joined tightly, forming the blood-brain barrier which protects the brain from toxins that might enter through the blood.
The brain is bathed in cerebrospinal fluid (CSF), which circulates between layers of the meninges and through cavities in the brain called ventricles. It is important both chemically for metabolism and mechanically for shock-prevention. For example, the human brain weighs about 1-1.5 kg or about 2-3 lb. The mass and density of the brain are such that it will begin to collapse under its own weight if unsupported by the CSF. The CSF allows the brain to float, easing the physical stress caused by the brain’s mass.
## Function
Vertebrate brains receive signals through nerves arriving from the sensors of the organism. These signals are then processed throughout the central nervous system; reactions are formulated based upon reflex and learned experiences. A similarly extensive nerve network delivers signals from a brain to control important muscles throughout the body. Anatomically, the majority of afferent and efferent nerves (with the exception of the cranial nerves) are connected to the spinal cord, which then transfers the signals to and from the brain.
Sensory input is processed by the brain to recognize danger, find food, identify potential mates, and perform more sophisticated functions. Visual, touch, and auditory sensory pathways of vertebrates are routed to specific nuclei of the thalamus and then to regions of the cerebral cortex that are specific to each sensory system. The visual system, the auditory system, and the somatosensory system. Olfactory pathways are routed to the olfactory bulb, then to various parts of the olfactory system. Taste is routed through the brainstem and then to other portions of the gustatory system.
To control movement the brain has several parallel systems of muscle control. The motor system controls voluntary muscle movement, aided by the motor cortex, cerebellum, and the basal ganglia. The system eventually projects to the spinal cord and then out to the muscle effectors. Nuclei in the brain stem control many involuntary muscle functions such as heart rate and breathing. In addition, many automatic acts (simple reflexes, locomotion) can be controlled by the spinal cord alone.
Brains also produce a portion of the body's hormones that can influence organs and glands elsewhere in a body—conversely, brains also react to hormones produced elsewhere in the body. In mammals, the hormones that regulate hormone production throughout the body are produced in the brain by the structure called the pituitary gland.
Evidence strongly suggests that developed brains derive consciousness from the complex interactions between the numerous systems within the brain. Cognitive processing in mammals occurs in the cerebral cortex but relies on midbrain and limbic functions as well. Among "younger" (in an evolutionary sense) vertebrates, advanced processing involves progressively rostral (forward) regions of the brain.
Hormones, incoming sensory information, and cognitive processing performed by the brain determine the brain state. Stimulus from any source can trigger a general arousal process that focuses cortical operations to processing of the new information. This focusing of cognition is known as attention. Cognitive priorities are constantly shifted by a variety of factors such as hunger, fatigue, belief, unfamiliar information, or threat. The simplest dichotomy related to the processing of threats is the fight-or-flight response mediated by the amygdala and other limbic structures.
### Neurotransmitter systems
Neurons expressing certain types of neurotransmitters sometimes form distinct systems, where activation of the system causes effects in large volumes of the brain, called volume transmission.
The major neurotransmitter systems are the noradrenaline (norepinephrine) system, the dopamine system, the serotonin system and the cholinergic system.
Drugs targeting the neurotransmitter of such systems affects the whole system, and explains the mode of action of many drugs;
- Cocaine, for example, blocks the reuptake of dopamine, leaving these neurotransmitters in the synaptic gap longer.
- Prozac is a selective serotonin reuptake inhibitor (SSRI), hence potentiating the effect of naturally released serotonin.
- AMPT prevents the conversion of tyrosine to L-DOPA, the precursor to dopamine; reserpine prevents dopamine storage within vesicles; and deprenyl inhibits monoamine oxidase (MAO)-B and thus increases dopamine levels.
Diseases may affect specific neurotransmitter systems. For example, Parkinson's disease is at least in part related to failure of dopaminergic cells in deep-brain nuclei, for example the substantia nigra. Treatments potentiating the effect of dopamine precursors have been proposed and effected, with moderate success.
A brief comparison of the major neurotransmitter systems follows:
## Pathology
Clinically, death is defined as an absence of brain activity as measured by EEG. Injuries to the brain tend to affect large areas of the organ, sometimes causing major deficits in intelligence, memory, and movement. Head trauma caused, for example, by vehicle and industrial accidents, is a leading cause of death in youth and middle age. In many cases, more damage is caused by resultant edema than by the impact itself. Stroke, caused by the blockage or rupturing of blood vessels in the brain, is another major cause of death from brain damage.
Other problems in the brain can be more accurately classified as diseases rather than injuries. Neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, motor neurone disease, and Huntington's disease are caused by the gradual death of individual neurons, leading to decrements in movement control, memory, and cognition. Currently only the symptoms of these diseases can be treated. Mental illnesses, such as clinical depression, schizophrenia, bipolar disorder, and post-traumatic stress disorder are brain diseases that impact personality and, typically, other aspects of mental and somatic function. These disorders may be treated by psychiatric therapy, pharmaceutical intervention, or through a combination of treatments; therapeutic effectiveness varies significantly among individuals.
Some infectious diseases affecting the brain are caused by viruses and bacteria. Infection of the meninges, the membrane that covers the brain, can lead to meningitis. Bovine spongiform encephalopathy (also known as mad cow disease), is deadly in cattle and humans and is linked to prions. Kuru is a similar prion-borne degenerative brain disease affecting humans. Both are linked to the ingestion of neural tissue, and may explain the tendency in some species to avoid cannibalism. Viral or bacterial causes have been reported in multiple sclerosis, Parkinson's disease, and are established causes of encephalopathy, and encephalomyelitis.
Many brain disorders are congenital. Tay-Sachs disease, Fragile X syndrome, and Down syndrome are all linked to genetic and chromosomal errors. Malfunctions in the embryonic development of the brain can be caused by genetic factors, drug use, nutritional deficiencies, and disease during a mother's pregnancy.
Certain brain disorders are treated by brain neurosurgeons while others are treated by neurologists and psychiatrists.
# Study of the brain
## Fields of study
Neuroscience seeks to understand the nervous system, including the brain, from a biological and computational perspective. Psychology seeks to understand behavior and the brain. Neurology refers to the medical applications of neuroscience. The brain is also one of the most important organs studied in psychiatry, the branch of medicine which exists to study, prevent, and treat mental disorders. Cognitive science seeks to unify neuroscience and psychology with other fields that concern themselves with the brain, such as computer science (artificial intelligence and similar fields) and philosophy.
## Methods of observation
Each method for observing activity in the brain has its advantages and drawbacks.
### Electrophysiology
Electrophysiology allows scientists to record the electrical activity of individual neurons or groups of neurons.
### EEG
By placing electrodes on the scalp one can record the summed electrical activity of the cortex in a technique known as electroencephalography (EEG). EEG measures the mass changes in electrical current from the cerebral cortex, but can only detect changes over large areas of the brain with very little sub-cortical activity.
### MEG
Apart from measuring the electric field around the skull it is possible to measure the magnetic field directly in a technique known as magnetoencephalography (MEG). This technique has the same temporal resolution as EEG but much better spatial resolution, although admittedly not as good as fMRI. The main advantage over fMRI is a direct relationship between neural activation and measurement.
### fMRI and PET
Functional magnetic resonance imaging (fMRI) measures changes in blood flow in the brain, but the activity of neurons is not directly measured, nor can it be distinguished whether this activity is inhibitory or excitatory. fMRI is a noninvasive, indirect method for measuring neural activity that is based on BOLD; Blood Oxygen Level Dependent changes. The changes in blood flow that occur in capillary beds in specific regions of the brain are thought to represent various neuronal activities (metabolism of synaptic reuptake). Similarly, a positron emission tomography (PET), is able to monitor glucose and oxygen metabolism as well as neurotransmitter activity in different areas within the brain which can be correlated to the level of activity in that region.
### Behavioral
Behavioral tests can measure symptoms of disease and mental performance, but can only provide indirect measurements of brain function and may not be practical in all animals. In humans however, a neurological exam can be done to determine the location of any trauma, lesion, or tumor within the brain, brain stem, or spinal cord.
### Anatomical
Autopsy analysis of the brain allows for the study of anatomy and protein expression patterns, but is only possible after the human or animal is dead. Magnetic resonance imaging (MRI) can be used to study the anatomy of a living creature and is widely used in both research and medicine.
## Other studies
Computer scientists have produced simulated "artificial neural networks" loosely based on the structure of neuron connections in the brain. Some artificial intelligence research seeks to replicate brain function—although not necessarily brain mechanisms—but as yet has been met with limited success.
Creating algorithms to mimic a biological brain is very difficult because the brain is not a static arrangement of circuits, but a network of vastly interconnected neurons that are constantly changing their connectivity and sensitivity. More recent work in both neuroscience and artificial intelligence models the brain using the mathematical tools of chaos theory and dynamical systems. Current research has also focused on recreating the neural structure of the brain with the aim of producing human-like cognition and artificial intelligence.
# As nourishment
Like most other internal organs, the brain can serve as nourishment. For example, in the Southern United States canned pork brain in gravy can be purchased for consumption as food. This form of brain is often fried with scrambled eggs to produce the famous "Eggs n' Brains". The brain of animals also features in French cuisine such as in the dish tête de veau, or head of calf. Although it might consist only of the outer meat of the skull and jaw, the full meal includes the brain, tongue, and glands. Similar delicacies from around the world include Mexican tacos de sesos made with cattle brain as well as squirrel brain in the US South. The Anyang tribe of Cameroon practiced a tradition in which a new tribal chief would consume the brain of a hunted gorilla while another senior member of the tribe would eat the heart. Indonesian cuisine specialty in Minangkabau cuisine also served beef brain in a gravy coconut milk named gulai otak (beef brain curry). Roasted or fried goat brain is eaten in south India and some parts of north India.
Consuming the brain and other nerve tissue of animals is not without risks. The first problem is that the makeup of the brain is 60% fat due to the myelin (which itself is 70% fat) insulating the axons of neurons and glia. As an example, a 140 g can of "pork brains in milk gravy", a single serving, contains 3500 milligrams of cholesterol, 1170% of our recommended daily intake.
Brain consumption can result in contracting fatal transmissible spongiform encephalopathies such as Variant Creutzfeldt-Jakob disease and other prion diseases in humans and mad cow disease in cattle. Another prion disease called kuru has been traced to a funerary ritual among the Fore people of Papua New Guinea in which those close to the dead would eat the brain of the deceased to create a sense of immortality. Some archaeological evidence suggests that the mourning rituals of European Neanderthals also involved the consumption of the brain. Because of the risk of being infected by prions one should always wear gloves when handling brains.
It is also well known in the hunting community that the brain of wild animals should not be consumed, due to the risk of chronic wasting disease. The brain is still useful to hunters, in that most animals have enough brain matter for use in the tanning of their own hides.
# Brain energy consumption
The neurons of the brain require a lot of energy. Although the brain represents only 2% of the body weight, it receives 15% of the cardiac output, 20% of total body oxygen consumption, and 25% of total body glucose utilization. The energy consumption for the brain to simply survive is 0.1 calories per minute, while this value can be as high as 1.5 calories per minute during crossword puzzle-solving. The demands of the brain limit its size in many species. Molossid bats and the Vespertilionid Nyctalus spp. have brains that have been reduced from the ancestral form to invest in wing-size for the sake of manoeuverability. This contrasts with fruit bats, which require more advanced neural structures and do not pursue their prey.
# Image Gallery
## MRI
(Images courtesy of RadsWiki)
- Normal brain
- Normal brain
- Normal brain
- Normal brain
- Normal brain
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- Normal brain
# Further reading
- Junqueira, L.C., and J. Carneiro (2003). Basic Histology: Text and Atlas, Tenth Edition. Lange Medical Books McGraw-Hill. ISBN 0-07-121565-4.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}
- Kinseher Richard, Geborgen in Liebe und Licht - Gemeinsame Ursache von Intuition, Déjà-vu-, Schutzengel-, und Nahtod-Erlebnissen, BoD, 2006, ISBN 3-8334-51963, German language: (A new theory: A LIVE-scan of the episodic memory, can be observed during near-death-experiences. The stored experiences are then judged by the topical intellect.)
- Sala, Sergio Della, editor. (1999). Mind myths: Exploring popular assumptions about the mind and brain. J. Wiley & Sons, New York. ISBN 0-471-98303-9.CS1 maint: Multiple names: authors list (link) CS1 maint: Extra text: authors list (link)
- Vander, A., J. Sherman, D. Luciano (2001). Human Physiology: The Mechanisms of Body Function. McGraw Hill Higher Education. ISBN 0-07-118088-5.CS1 maint: Multiple names: authors list (link)
- Scaruffi, Piero. The Nature of Consciousness. Omniware. ISBN 0-9765531-1-2. | Brain
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
In animals, the brain is the control center of the central nervous system, responsible for behavior. The brain is located in the head, protected by the skull and close to the primary sensory apparatus of vision, hearing, equilibrioception (balance), sense of taste, and olfaction (smell). While all vertebrates have a brain, most invertebrates have either a centralized brain or collections of individual ganglia. Some animals such as cnidarians and echinoderms do not have a centralized brain, instead have a decentralized nervous system, while animals such as sponges lack both a brain and nervous system entirely. Brains can be extremely complex. For example, the human brain contains roughly 23 billion neurons, each linked to as many as 10,000 other neurons.
# Overview
The brain is the central information-processing organ of the body. It innervates the head through cranial nerves, and it communicates with the spinal cord, which innervates the body through spinal nerves. Nervous fibers transmitting signals from the brain are called efferent fibers. The fibers transmitting signals to the brain are called afferent fibers (or sensory fibers). Nerves can be afferent, efferent or mixed (i.e., containing both types of fibers).
The brain is the site of reason and intelligence, which include such components as cognition, perception, attention, memory and emotion. The brain is also responsible for control of posture and movements. It makes possible cognitive, motor and other forms of learning. The brain can perform a variety of functions automatically, without the need for conscious awareness, such as coordination of sensory systems (eg. sensory gating and multisensory integration), walking, and homeostatic body functions such as blood pressure, fluid balance, and body temperature.
The Cerebellum controls balance and movement. Without it, movements would not be coordinated.
Many functions are controlled by coordinated activity of the brain and spinal cord. Moreover, some behaviors such as simple reflexes and basic locomotion, can be executed under spinal cord control alone.
The brain undergoes transitions from wakefulness to sleep (and subtypes of these states). These state transitions are crucially important for proper brain functioning. (For example, it is believed that sleep is important for knowledge consolidation, as the neurons appear to organize the day's stimuli during deep sleep by randomly firing off the most recently used neuron pathways; additionally, without sleep, normal subjects are observed to develop symptoms resembling mental illness, even auditory hallucinations). Every brain state is associated with characteristic brain waves.
Neurons are electrically active brain cells that process information, whereas Glial cells perform supporting function. In addition to being electrically active, neurons constantly synthesize neurotransmitters. Neurons modify their properties (guided by gene expression) under the influence of their input signals. This plasticity underlies learning and adaptation. It is notable that some unused neuron pathways (constructions which have become physically isolated from other cells) may continue to exist long after the memory is absent from consciousness, possibly developing the subconscious.
The study of the brain is known as neuroscience, a field of biology aimed at understanding the functions of the brain at every level, from the molecular up to the psychological. There is also a branch of psychology that deals with the anatomy and physiology of the brain, known as biological psychology. This field of study focuses on each individual part of the brain and how it affects behavior.
# History
Early views on the function of the brain regarded it as little more than cranial stuffing. In Ancient Egypt, from the late Middle Kingdom onwards, in preparation for mummification, the brain was regularly removed, for it was the heart that was assumed to be the seat of intelligence. According to Herodotus, during the first step of mummification, "The most perfect practice is to extract as much of the brain as possible with an iron hook, and what the hook cannot reach is mixed with drugs." Over the next five-thousand years, this view came to be reversed; the brain is now known to be seat of intelligence, although idiomatic variations of the former remain, as in memorizing something "by heart".[1]
The first thoughts on the field of psychology came from ancient philosophers, such as Aristotle. As thinkers became more in tune with biomedical research over time, as was the case with medieval psychologists such as Alhazen and Avicenna for example, the concepts of experimental psychology and clinical psychology began emerging. From that point, different branches of psychology emerged with different individuals creating new ideas, with modern psychologists such as Freud and Jung contributing to the field.
# Mind and brain
The distinction between the mind and the brain is fundamental in philosophy of mind. The mind-body problem is one of the central problems in the history of philosophy. The brain is the physical and biological matter contained within the skull, responsible for electrochemical neuronal processes. The mind, in contrast, consists in mental attributes, such as beliefs, desires, perceptions, and so on. There are scientifically demonstrable correlations between mental events and neuronal events; the philosophical question is whether these phenomena are identical or are related in some other way.
The philosophical positions on the mind-body problem fall into two main categories. The first category is dualism, according to which the mind exists independently of the brain. Dualist theories are further divided into substance dualism and property dualism. Descartes is perhaps the most prominent substance dualist, while property dualism is more popular among contemporary dualists like David Chalmers. The second category is materialism, according to which mental phenomena are identical to neuronal phenomena. A third category of view, idealism, claims that only mental substances and phenomena exist. This view, most prominently held by 18th century English philosopher George Berkeley, has few contemporary adherents.
Both dualism and materialism face serious philosophical challenges. Dualism requires that we admit non-physical substances or properties into our ontology, a move that places dualism in apparent conflict with the scientific world view. Materialism, on the other hand, must provide an explanation of how two seemingly different kinds of phenomena - the mental and the physical - could be identical. This challenge can be seen by noting that mental phenomena have certain characteristics - particularly intentionality and phenomenal character - that physical phenomena do not, and seemingly could not, have.
# Comparative anatomy
Three groups of animals have notably complex brains: the arthropods (insects, crustaceans, arachnids, and others), the cephalopods (octopuses, squids, and similar mollusks), and the craniates (vertebrates and hagfish).[2] The brain of arthropods and cephalopods arises from twin parallel nerve cords that extend through the body of the animal. Arthropods have a central brain with three divisions and large optical lobes behind each eye for visual processing.[2]
The brain of craniates develops from the anterior section of a single dorsal nerve cord, which later becomes the spinal cord.[3] In craniates, the brain is protected by the bones of the skull.
Mammals have a six-layered neocortex (or homotypic cortex, neopallium), in addition to having some parts of the brain that are allocortex.[3] In mammals, increasing convolutions of the brain are characteristic of animals with more advanced brains. These convolutions provide a larger surface area for a greater number of neurons while keeping the volume of the brain compact enough to fit inside the skull. The folding allows more grey matter to fit into a smaller volume, similar to a really long slinky being able to fit into a tiny box when completely pushed together. The folds are called gyri, while the spaces between the folds are called sulci.
In birds, the part of the brain that functionally corresponds to the neocortex is called nidopallium and derives from a different part of the brain. Some birds (like corvids and parrots) have intelligence equal to great apes, but even in these, the brain region that forms the mammalian neocortex is in fact almost entirely absent.
Although the general histology of the brain is similar from person to person, the structural anatomy can differ. Apart from the gross embryological divisions of the brain, the location of specific gyri and sulci, primary sensory regions, and other structures differs between species.
## Mammals and other vertebrates
The telencephalon (cerebrum) is the largest region of the mammalian brain. This is the structure that is most easily visible in brain specimens, and is what most people associate with the "brain". In humans and several other animals, the fissures (sulci) and convolutions (gyri) give the brain a wrinkled appearance. In non-mammalian vertebrates with no cerebrum, the metencephalon is the highest center in the brain. Because humans walk upright, there is a flexure, or bend, in the brain between the brain stem and the cerebrum. Other vertebrates do not have this flexure. Generally, comparing the locations of certain brain structures between humans and other vertebrates often reveals a number of differences.
Behind (or in humans, below) the cerebrum is the cerebellum. The cerebellum is known to be involved in the control of movement,[3] and is connected by thick white matter fibers (cerebellar peduncles) to the pons.[4] The cerebrum has two cerebral hemispheres. The cerebellum also has hemispheres. The telencephalic hemispheres are connected by the corpus callosum, another large white matter tract. An outgrowth of the telencephalon called the olfactory bulb is a major structure in many animals, but in humans and other primates it is relatively small.
Vertebrate nervous systems are distinguished by bilaterally symmetrical encephalization. Encephalization refers to the tendency for more complex organisms to gain larger brains through evolutionary time. Larger vertebrates develop a complex, layered and interconnected neuronal circuitry. In modern species most closely related to the first vertebrates, brains are covered with gray matter that has a three-layer structure (allocortex). Their brains also contain deep brain nuclei and fiber tracts forming the white matter. Most regions of the human cerebral cortex have six layers of neurons (neocortex).[4]
### Vertebrate brain regions
(See related article at List of regions in the human brain)
According to the hierarchy based on embryonic and evolutionary development, chordate brains are composed of the three regions that later develop into five total divisions:
- Rhombencephalon (hindbrain)
Myelencephalon
Metencephalon
- Myelencephalon
- Metencephalon
- Mesencephalon (midbrain)
- Prosencephalon (forebrain)
Diencephalon
Telencephalon
- Diencephalon
- Telencephalon
The brain can also be classified according to function, including divisions such as:
- Limbic system
- Sensory systems
Visual system
Olfactory system
Gustatory system
Auditory system
Somatosensory system
- Visual system
- Olfactory system
- Gustatory system
- Auditory system
- Somatosensory system
- Motor system
- Associative areas
In recent years it was realized that certain birds have developed high intelligence entirely convergently from mammals such as humans. Hence, the functional areas of the avian brain have been redefined by the Avian Brain Nomenclature Consortium.
### Humans
The structure of the human brain differs from that of other animals in several important ways. These differences allow for many abilities over and above those of other animals, such as advanced cognitive skills. Human encephalization is especially pronounced in the neocortex, the most complex part of the cerebral cortex. The proportion of the human brain that is devoted to the neocortex—especially to the prefrontal cortex—is larger than in all other mammals (indeed larger than in all animals, although only in mammals has the neocortex evolved to fulfill this kind of function).
Humans have unique neural capacities, but much of their brain structure is similar to that of other mammals. Basic systems that alert the nervous system to stimulus, that sense events in the environment, and monitor the condition of the body are similar to those of even non-mammalian vertebrates. The neural circuitry underlying human consciousness includes both the advanced neocortex and prototypical structures of the brainstem. The human brain also has a massive number of synaptic connections allowing for a great deal of parallel processing.
# Neurobiology
The brain is composed of two broad classes of cells, neurons and glia, both of which contain several different cell types which perform different functions. Interconnected neurons form neural networks (or neural ensembles). These networks are similar to man-made electrical circuits in that they contain circuit elements (neurons) connected by biological wires (nerve fibers). These do not form simple one-to-one electrical circuits like many man-made circuits, however. Typically neurons connect to at least a thousand other neurons.[5] These highly specialized circuits make up systems which are the basis of perception, different types of action, and higher cognitive function.
## Structure
Template:Neuron map
Neurons are the cells that generate action potentials and convey information to other cells; these constitute the essential class of brain cells.
In addition to neurons, the brain contains glial cells in a roughly 10:1 proportion to neurons. Glial cells ("glia" is Greek for “glue”) form a support system for neurons. They create the insulating myelin, provide structure to the neuronal network, manage waste, and clean up neurotransmitters. Most types of glia in the brain are present in the entire nervous system. Exceptions include the oligodendrocytes which myelinate neural axons (a role performed by Schwann cells in the peripheral nervous system). The myelin in the oligodendrocytes insulates the axons of some neurons. White matter in the brain is myelinated neurons, while grey matter contains mostly cell soma, dendrites, and unmyelinated portions of axons and glia. The space between neurons is filled with dendrites as well as unmyelinated segments of axons; this area is referred to as the neuropil.
In mammals, the brain is surrounded by connective tissues called the meninges, a system of membranes that separate the skull from the brain. This three-layered covering is composed of (from the outside in) the dura mater, arachnoid mater, and pia mater. The arachnoid and pia are physically connected and thus often considered as a single layer, the pia-arachnoid. Below the arachnoid is the subarachnoid space which contains cerebrospinal fluid, a substance that protects the nervous system. Blood vessels enter the central nervous system through the perivascular space above the pia mater. The cells in the blood vessel walls are joined tightly, forming the blood-brain barrier which protects the brain from toxins that might enter through the blood.
The brain is bathed in cerebrospinal fluid (CSF), which circulates between layers of the meninges and through cavities in the brain called ventricles. It is important both chemically for metabolism and mechanically for shock-prevention. For example, the human brain weighs about 1-1.5 kg or about 2-3 lb. The mass and density of the brain are such that it will begin to collapse under its own weight if unsupported by the CSF. The CSF allows the brain to float, easing the physical stress caused by the brain’s mass.
## Function
Vertebrate brains receive signals through nerves arriving from the sensors of the organism. These signals are then processed throughout the central nervous system; reactions are formulated based upon reflex and learned experiences. A similarly extensive nerve network delivers signals from a brain to control important muscles throughout the body. Anatomically, the majority of afferent and efferent nerves (with the exception of the cranial nerves) are connected to the spinal cord, which then transfers the signals to and from the brain.
Sensory input is processed by the brain to recognize danger, find food, identify potential mates, and perform more sophisticated functions. Visual, touch, and auditory sensory pathways of vertebrates are routed to specific nuclei of the thalamus and then to regions of the cerebral cortex that are specific to each sensory system. The visual system, the auditory system, and the somatosensory system. Olfactory pathways are routed to the olfactory bulb, then to various parts of the olfactory system. Taste is routed through the brainstem and then to other portions of the gustatory system.
To control movement the brain has several parallel systems of muscle control. The motor system controls voluntary muscle movement, aided by the motor cortex, cerebellum, and the basal ganglia. The system eventually projects to the spinal cord and then out to the muscle effectors. Nuclei in the brain stem control many involuntary muscle functions such as heart rate and breathing. In addition, many automatic acts (simple reflexes, locomotion) can be controlled by the spinal cord alone.
Brains also produce a portion of the body's hormones that can influence organs and glands elsewhere in a body—conversely, brains also react to hormones produced elsewhere in the body. In mammals, the hormones that regulate hormone production throughout the body are produced in the brain by the structure called the pituitary gland.
Evidence strongly suggests that developed brains derive consciousness from the complex interactions between the numerous systems within the brain. Cognitive processing in mammals occurs in the cerebral cortex but relies on midbrain and limbic functions as well. Among "younger" (in an evolutionary sense) vertebrates, advanced processing involves progressively rostral (forward) regions of the brain.
Hormones, incoming sensory information, and cognitive processing performed by the brain determine the brain state. Stimulus from any source can trigger a general arousal process that focuses cortical operations to processing of the new information. This focusing of cognition is known as attention. Cognitive priorities are constantly shifted by a variety of factors such as hunger, fatigue, belief, unfamiliar information, or threat. The simplest dichotomy related to the processing of threats is the fight-or-flight response mediated by the amygdala and other limbic structures.
### Neurotransmitter systems
Neurons expressing certain types of neurotransmitters sometimes form distinct systems, where activation of the system causes effects in large volumes of the brain, called volume transmission.
The major neurotransmitter systems are the noradrenaline (norepinephrine) system, the dopamine system, the serotonin system and the cholinergic system.
Drugs targeting the neurotransmitter of such systems affects the whole system, and explains the mode of action of many drugs;
- Cocaine, for example, blocks the reuptake of dopamine, leaving these neurotransmitters in the synaptic gap longer.
- Prozac is a selective serotonin reuptake inhibitor (SSRI), hence potentiating the effect of naturally released serotonin.
- AMPT prevents the conversion of tyrosine to L-DOPA, the precursor to dopamine; reserpine prevents dopamine storage within vesicles; and deprenyl inhibits monoamine oxidase (MAO)-B and thus increases dopamine levels.
Diseases may affect specific neurotransmitter systems. For example, Parkinson's disease is at least in part related to failure of dopaminergic cells in deep-brain nuclei, for example the substantia nigra. Treatments potentiating the effect of dopamine precursors have been proposed and effected, with moderate success.
A brief comparison of the major neurotransmitter systems follows:
## Pathology
Clinically, death is defined as an absence of brain activity as measured by EEG. Injuries to the brain tend to affect large areas of the organ, sometimes causing major deficits in intelligence, memory, and movement. Head trauma caused, for example, by vehicle and industrial accidents, is a leading cause of death in youth and middle age. In many cases, more damage is caused by resultant edema than by the impact itself. Stroke, caused by the blockage or rupturing of blood vessels in the brain, is another major cause of death from brain damage.
Other problems in the brain can be more accurately classified as diseases rather than injuries. Neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, motor neurone disease, and Huntington's disease are caused by the gradual death of individual neurons, leading to decrements in movement control, memory, and cognition. Currently only the symptoms of these diseases can be treated. Mental illnesses, such as clinical depression, schizophrenia, bipolar disorder, and post-traumatic stress disorder are brain diseases that impact personality and, typically, other aspects of mental and somatic function. These disorders may be treated by psychiatric therapy, pharmaceutical intervention, or through a combination of treatments; therapeutic effectiveness varies significantly among individuals.
Some infectious diseases affecting the brain are caused by viruses and bacteria. Infection of the meninges, the membrane that covers the brain, can lead to meningitis. Bovine spongiform encephalopathy (also known as mad cow disease), is deadly in cattle and humans and is linked to prions. Kuru is a similar prion-borne degenerative brain disease affecting humans. Both are linked to the ingestion of neural tissue, and may explain the tendency in some species to avoid cannibalism. Viral or bacterial causes have been reported in multiple sclerosis, Parkinson's disease, and are established causes of encephalopathy, and encephalomyelitis.
Many brain disorders are congenital. Tay-Sachs disease, Fragile X syndrome, and Down syndrome are all linked to genetic and chromosomal errors. Malfunctions in the embryonic development of the brain can be caused by genetic factors, drug use, nutritional deficiencies, and disease during a mother's pregnancy.
Certain brain disorders are treated by brain neurosurgeons while others are treated by neurologists and psychiatrists.
# Study of the brain
## Fields of study
Neuroscience seeks to understand the nervous system, including the brain, from a biological and computational perspective. Psychology seeks to understand behavior and the brain. Neurology refers to the medical applications of neuroscience. The brain is also one of the most important organs studied in psychiatry, the branch of medicine which exists to study, prevent, and treat mental disorders.[7][8][9] Cognitive science seeks to unify neuroscience and psychology with other fields that concern themselves with the brain, such as computer science (artificial intelligence and similar fields) and philosophy.
## Methods of observation
Each method for observing activity in the brain has its advantages and drawbacks.
### Electrophysiology
Electrophysiology allows scientists to record the electrical activity of individual neurons or groups of neurons.
### EEG
By placing electrodes on the scalp one can record the summed electrical activity of the cortex in a technique known as electroencephalography (EEG). EEG measures the mass changes in electrical current from the cerebral cortex, but can only detect changes over large areas of the brain with very little sub-cortical activity.
### MEG
Apart from measuring the electric field around the skull it is possible to measure the magnetic field directly in a technique known as magnetoencephalography (MEG). This technique has the same temporal resolution as EEG but much better spatial resolution, although admittedly not as good as fMRI. The main advantage over fMRI is a direct relationship between neural activation and measurement.
### fMRI and PET
Functional magnetic resonance imaging (fMRI) measures changes in blood flow in the brain, but the activity of neurons is not directly measured, nor can it be distinguished whether this activity is inhibitory or excitatory. fMRI is a noninvasive, indirect method for measuring neural activity that is based on BOLD; Blood Oxygen Level Dependent changes. The changes in blood flow that occur in capillary beds in specific regions of the brain are thought to represent various neuronal activities (metabolism of synaptic reuptake). Similarly, a positron emission tomography (PET), is able to monitor glucose and oxygen metabolism as well as neurotransmitter activity in different areas within the brain which can be correlated to the level of activity in that region.
### Behavioral
Behavioral tests can measure symptoms of disease and mental performance, but can only provide indirect measurements of brain function and may not be practical in all animals. In humans however, a neurological exam can be done to determine the location of any trauma, lesion, or tumor within the brain, brain stem, or spinal cord.
### Anatomical
Autopsy analysis of the brain allows for the study of anatomy and protein expression patterns, but is only possible after the human or animal is dead. Magnetic resonance imaging (MRI) can be used to study the anatomy of a living creature and is widely used in both research and medicine.
## Other studies
Computer scientists have produced simulated "artificial neural networks" loosely based on the structure of neuron connections in the brain. Some artificial intelligence research seeks to replicate brain function—although not necessarily brain mechanisms—but as yet has been met with limited success.
Creating algorithms to mimic a biological brain is very difficult because the brain is not a static arrangement of circuits, but a network of vastly interconnected neurons that are constantly changing their connectivity and sensitivity. More recent work in both neuroscience and artificial intelligence models the brain using the mathematical tools of chaos theory and dynamical systems. Current research has also focused on recreating the neural structure of the brain with the aim of producing human-like cognition and artificial intelligence.
# As nourishment
Like most other internal organs, the brain can serve as nourishment. For example, in the Southern United States canned pork brain in gravy can be purchased for consumption as food. This form of brain is often fried with scrambled eggs to produce the famous "Eggs n' Brains".[10] The brain of animals also features in French cuisine such as in the dish tête de veau, or head of calf. Although it might consist only of the outer meat of the skull and jaw, the full meal includes the brain, tongue, and glands. Similar delicacies from around the world include Mexican tacos de sesos made with cattle brain as well as squirrel brain in the US South.[11] The Anyang tribe of Cameroon practiced a tradition in which a new tribal chief would consume the brain of a hunted gorilla while another senior member of the tribe would eat the heart.[12] Indonesian cuisine specialty in Minangkabau cuisine also served beef brain in a gravy coconut milk named gulai otak (beef brain curry). Roasted or fried goat brain is eaten in south India and some parts of north India.
Consuming the brain and other nerve tissue of animals is not without risks. The first problem is that the makeup of the brain is 60% fat due to the myelin (which itself is 70% fat) insulating the axons of neurons and glia.[13] As an example, a 140 g can of "pork brains in milk gravy", a single serving, contains 3500 milligrams of cholesterol, 1170% of our recommended daily intake.[14]
Brain consumption can result in contracting fatal transmissible spongiform encephalopathies such as Variant Creutzfeldt-Jakob disease and other prion diseases in humans and mad cow disease in cattle.[15] Another prion disease called kuru has been traced to a funerary ritual among the Fore people of Papua New Guinea in which those close to the dead would eat the brain of the deceased to create a sense of immortality.[16] Some archaeological evidence suggests that the mourning rituals of European Neanderthals also involved the consumption of the brain.[17] Because of the risk of being infected by prions one should always wear gloves when handling brains.
It is also well known in the hunting community that the brain of wild animals should not be consumed, due to the risk of chronic wasting disease. The brain is still useful to hunters, in that most animals have enough brain matter for use in the tanning of their own hides.
# Brain energy consumption
The neurons of the brain require a lot of energy. Although the brain represents only 2% of the body weight, it receives 15% of the cardiac output, 20% of total body oxygen consumption, and 25% of total body glucose utilization. The energy consumption for the brain to simply survive is 0.1 calories per minute, while this value can be as high as 1.5 calories per minute during crossword puzzle-solving.[18] The demands of the brain limit its size in many species. Molossid bats and the Vespertilionid Nyctalus spp. have brains that have been reduced from the ancestral form to invest in wing-size for the sake of manoeuverability. This contrasts with fruit bats, which require more advanced neural structures and do not pursue their prey.[19]
Template:Portalpar
# Image Gallery
## MRI
(Images courtesy of RadsWiki)
- Normal brain
- Normal brain
- Normal brain
- Normal brain
- Normal brain
- Normal brain
- Normal brain
# Further reading
- Junqueira, L.C., and J. Carneiro (2003). Basic Histology: Text and Atlas, Tenth Edition. Lange Medical Books McGraw-Hill. ISBN 0-07-121565-4.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}
- Kinseher Richard, Geborgen in Liebe und Licht - Gemeinsame Ursache von Intuition, Déjà-vu-, Schutzengel-, und Nahtod-Erlebnissen, BoD, 2006, ISBN 3-8334-51963, German language: (A new theory: A LIVE-scan of the episodic memory, can be observed during near-death-experiences. The stored experiences are then judged by the topical intellect.)
- Sala, Sergio Della, editor. (1999). Mind myths: Exploring popular assumptions about the mind and brain. J. Wiley & Sons, New York. ISBN 0-471-98303-9.CS1 maint: Multiple names: authors list (link) CS1 maint: Extra text: authors list (link)
- Vander, A., J. Sherman, D. Luciano (2001). Human Physiology: The Mechanisms of Body Function. McGraw Hill Higher Education. ISBN 0-07-118088-5.CS1 maint: Multiple names: authors list (link)
- Scaruffi, Piero. The Nature of Consciousness. Omniware. ISBN 0-9765531-1-2. | https://www.wikidoc.org/index.php/Brain | |
fcfbeb2b992dad70d0c00df68deb5fa171d5d3c0 | wikidoc | Brass | Brass
Brass is any alloy of copper and zinc; the proportions of zinc and copper can be varied to create a range of brasses with varying properties. In comparison, bronze is principally an alloy of copper and tin. Despite this distinction, some types of brasses are called bronzes. Brass is a substitutional alloy. It is used for decoration for its bright gold-like appearance; for applications where low friction is required such as locks, gears, bearings, ammunition, and valves; for plumbing and electrical applications; and extensively in musical instruments such as horns and bells for its acoustic properties.
Brass has a muted yellow color, somewhat similar to gold. It is relatively resistant to tarnishing, and is often used as decoration and for coins.
Brass has likely been known to humans since prehistoric times, even before zinc itself was discovered. It was produced by melting copper together with calamine, a zinc ore. In the German village of Breinigerberg an ancient Roman settlement was discovered where a calamine ore mine existed. During the melting process, the zinc is extracted from the calamine and mixes with the copper. Pure zinc, on the other hand, has too low a boiling point to have been produced by ancient metalworking techniques. The many references to 'brass' appearing throughout the King James Bible are thought to signify another bronze alloy, or copper, rather than the strict modern definition of 'brass'.
# Properties
The malleability and acoustic properties of brass have made it the metal of choice for brass musical instruments such as the trombone, tuba, trumpet, euphonium, and the French horn. Even though the saxophone is classified as a woodwind instrument and the harmonica is a free reed aerophone, both are also often made from brass. In organ pipes designed as "reed" pipes, brass strips are used as the "reeds".
Brass has higher malleability than copper or zinc. The relatively low melting point of brass (900 to 940°C, depending on composition) and its flow characteristics make it a relatively easy material to cast. By varying the proportions of copper and zinc, the properties of the brass can be changed, allowing hard and soft brasses.
Today almost 90% of all brass alloys are recycled. Because most brass is nonmagnetic, it can be separated from ferrous scrap by passing the scrap near a powerful magnet. Brass scrap is collected and transported to the foundry where it is melted and recast into billets. Billets are later heated and extruded into the desired form and size.
Aluminum makes brass stronger and more corrosion resistant. Aluminum also causes a highly beneficial hard layer of aluminium oxide (Al2O3) to be formed on the surface that is thin, transparent and self healing. Tin has a similar effect and finds its use especially in sea water applications (naval brasses). Combinations of iron, aluminum, silicon and manganese make brass wear and tear resistant. A well known alloy used in the automotive industry is 'LDM C673', where the combination of manganese and silicon leads to a strong and resistant brass.
The so called dezincification resistant (DZR) brasses, like alloy 'LDM G563' (known for its brand name 'Enkotal'), are used where there is a large corrosion risk and where normal brasses do not meet the standards. Applications with high water temperatures, chlorides present or deviating water qualities (soft water) play a role. DZR-brass is excellent in water boiler systems. This brass alloy must be produced with great care, with special attention placed on a balanced composition and proper production temperatures and parameters to avoid long-term failures. Drunen, Netherlands, has the only active production facility which makes these high grade brass alloys.
The copper in brass makes brass germicidal, via the oligodynamic effect. For example, brass doorknobs disinfect themselves of many bacteria within eight hours . This effect is important in hospitals, but useful in many contexts.
Brass door hardware is generally lacquered when new, which prevents tarnishing of the metal for a few years when located outside (and indefinitely when located indoors). After this most manufacturers recommend that the lacquer is removed (e.g. with paint stripper) and the items regularly polished to maintain a bright finish. Unlacquered brass weathers more attractively than brass with deteriorated lacquer, even if polishing is not carried out. Freshly polished brass is similar to gold in appearance, but becomes more reddish within days of exposure to the elements. A traditional polish is Brasso.
Brass was used to make fan blades, fan cages and motor bearings in many antique fans that date before the 1930s. Brass can be used for fixings for use in cryogenic systems, however its use is not limited to this.
The density of brass is approximately 8.4 g/cm3.
# Brass types
- Admiralty brass contains 30% zinc and 1% tin which inhibits dezincification in most environments.
- Alpha brasses (Prince's metal), with less than 35% zinc, are malleable, can be worked cold, and are used in pressing, forging, or similar applications. They contain only one phase, with face-centered cubic crystal structure.
- Alpha-beta brass (Muntz metal), also called duplex brass, is 35-45% zinc and is suited for hot working. It contains both α and β' phase; the β'-phase is body-centered cubic and is harder and stronger than α. Alpha-beta brasses are usually worked hot.
- Aluminum brass contains aluminum, which improves its corrosion resistance. Used in Euro coins (Nordic gold).
- Arsenical brass contains an addition of arsenic and frequently aluminium and is used for boiler fireboxes.
- Beta brasses, with 45-50% zinc content, can only be worked hot, and are harder, stronger, and suitable for casting.
- Cartridge brass is a 30% zinc brass with good cold working properties.
- Common brass, or rivet brass, is a 37% zinc brass, cheap and standard for cold working.
- DZR brass is Dezincification resistant Brass with a small percentage of Arsenic.
- High brass, contains 65% copper and 35% zinc, has a high tensile strength and is used for springs, screws, rivets.
- Leaded brass is an alpha-beta brass with an addition of lead. It has excellent machinability.
- Low brass is a copper-zinc alloy containing 20% zinc with a light golden color, excellent ductility and is used for flexible metal hoses and metal bellows.
- Naval brass, similar to admiralty brass, is a 40% zinc brass and 1% tin.
- Red brass, while not technically brass, is an American term for CuZnSn alloy known as gunmetal.
- White brass contains more than 50% zinc and is too brittle for general use.
- Yellow brass is an American term for 33% zinc brass.
- Gilding metal is the softest type of brass commonly available. An alloy of 95% copper and 5% zinc, gilding metal is typically used for ammunition components. | Brass
Brass is any alloy of copper and zinc; the proportions of zinc and copper can be varied to create a range of brasses with varying properties.[1] In comparison, bronze is principally an alloy of copper and tin.[2] Despite this distinction, some types of brasses are called bronzes. Brass is a substitutional alloy. It is used for decoration for its bright gold-like appearance; for applications where low friction is required such as locks, gears, bearings, ammunition, and valves; for plumbing and electrical applications; and extensively in musical instruments such as horns and bells for its acoustic properties.
Brass has a muted yellow color, somewhat similar to gold. It is relatively resistant to tarnishing, and is often used as decoration and for coins.
Brass has likely been known to humans since prehistoric times, even before zinc itself was discovered. It was produced by melting copper together with calamine, a zinc ore. In the German village of Breinigerberg an ancient Roman settlement was discovered where a calamine ore mine existed. During the melting process, the zinc is extracted from the calamine and mixes with the copper. Pure zinc, on the other hand, has too low a boiling point to have been produced by ancient metalworking techniques. The many references to 'brass' appearing throughout the King James Bible are thought to signify another bronze alloy, or copper, rather than the strict modern definition of 'brass'.[3]
# Properties
The malleability and acoustic properties of brass have made it the metal of choice for brass musical instruments such as the trombone, tuba, trumpet, euphonium, and the French horn. Even though the saxophone is classified as a woodwind instrument and the harmonica is a free reed aerophone, both are also often made from brass. In organ pipes designed as "reed" pipes, brass strips are used as the "reeds".
Brass has higher malleability than copper or zinc. The relatively low melting point of brass (900 to 940°C, depending on composition) and its flow characteristics make it a relatively easy material to cast. By varying the proportions of copper and zinc, the properties of the brass can be changed, allowing hard and soft brasses.
Today almost 90% of all brass alloys are recycled. Because most brass is nonmagnetic, it can be separated from ferrous scrap by passing the scrap near a powerful magnet. Brass scrap is collected and transported to the foundry where it is melted and recast into billets. Billets are later heated and extruded into the desired form and size.
Aluminum makes brass stronger and more corrosion resistant. Aluminum also causes a highly beneficial hard layer of aluminium oxide (Al2O3) to be formed on the surface that is thin, transparent and self healing. Tin has a similar effect and finds its use especially in sea water applications (naval brasses). Combinations of iron, aluminum, silicon and manganese make brass wear and tear resistant. A well known alloy used in the automotive industry is 'LDM C673', where the combination of manganese and silicon leads to a strong and resistant brass.
The so called dezincification resistant (DZR) brasses, like alloy 'LDM G563' (known for its brand name 'Enkotal'), are used where there is a large corrosion risk and where normal brasses do not meet the standards. Applications with high water temperatures, chlorides present or deviating water qualities (soft water) play a role. DZR-brass is excellent in water boiler systems. This brass alloy must be produced with great care, with special attention placed on a balanced composition and proper production temperatures and parameters to avoid long-term failures. Drunen, Netherlands, has the only active production facility which makes these high grade brass alloys.
The copper in brass makes brass germicidal, via the oligodynamic effect. For example, brass doorknobs disinfect themselves of many bacteria within eight hours [2]. This effect is important in hospitals, but useful in many contexts.
Brass door hardware is generally lacquered when new, which prevents tarnishing of the metal for a few years when located outside (and indefinitely when located indoors). After this most manufacturers recommend that the lacquer is removed (e.g. with paint stripper) and the items regularly polished to maintain a bright finish. Unlacquered brass weathers more attractively than brass with deteriorated lacquer, even if polishing is not carried out. Freshly polished brass is similar to gold in appearance, but becomes more reddish within days of exposure to the elements. A traditional polish is Brasso.
Brass was used to make fan blades, fan cages and motor bearings in many antique fans that date before the 1930s. Brass can be used for fixings for use in cryogenic systems, however its use is not limited to this.[4]
The density of brass is approximately 8.4 g/cm3.
# Brass types
- Admiralty brass contains 30% zinc and 1% tin which inhibits dezincification in most environments.
- Alpha brasses (Prince's metal), with less than 35% zinc, are malleable, can be worked cold, and are used in pressing, forging, or similar applications. They contain only one phase, with face-centered cubic crystal structure.
- Alpha-beta brass (Muntz metal), also called duplex brass, is 35-45% zinc and is suited for hot working. It contains both α and β' phase; the β'-phase is body-centered cubic and is harder and stronger than α. Alpha-beta brasses are usually worked hot.
- Aluminum brass contains aluminum, which improves its corrosion resistance. Used in Euro coins (Nordic gold).
- Arsenical brass contains an addition of arsenic and frequently aluminium and is used for boiler fireboxes.
- Beta brasses, with 45-50% zinc content, can only be worked hot, and are harder, stronger, and suitable for casting.
- Cartridge brass is a 30% zinc brass with good cold working properties.
- Common brass, or rivet brass, is a 37% zinc brass, cheap and standard for cold working.
- DZR brass is Dezincification resistant Brass with a small percentage of Arsenic.
- High brass, contains 65% copper and 35% zinc, has a high tensile strength and is used for springs, screws, rivets.
- Leaded brass is an alpha-beta brass with an addition of lead. It has excellent machinability.
- Low brass is a copper-zinc alloy containing 20% zinc with a light golden color, excellent ductility and is used for flexible metal hoses and metal bellows.
- Naval brass, similar to admiralty brass, is a 40% zinc brass and 1% tin.
- Red brass, while not technically brass, is an American term for CuZnSn alloy known as gunmetal.
- White brass contains more than 50% zinc and is too brittle for general use.
- Yellow brass is an American term for 33% zinc brass.
- Gilding metal is the softest type of brass commonly available. An alloy of 95% copper and 5% zinc, gilding metal is typically used for ammunition components. | https://www.wikidoc.org/index.php/Brass | |
a686724894b1bb1c6a02a2d7ccc3ac958f3829e8 | wikidoc | Braxy | Braxy
Braxy is an inflammatory disease in the abomasal lining of sheep caused by the bacterium Clostridium septicum (aka Bacillus septicus).
Braxy is often brought on by a change from succulent food to dry (or icy) food. It is usually seen in young sheep, in particular those not protected with a Clostridial vaccine.
The mutton affected with this disease can also be referred to as braxy. | Braxy
Braxy is an inflammatory disease in the abomasal lining of sheep caused by the bacterium Clostridium septicum (aka Bacillus septicus).
Braxy is often brought on by a change from succulent food to dry (or icy) food. It is usually seen in young sheep, in particular those not protected with a Clostridial vaccine.
The mutton affected with this disease can also be referred to as braxy. | https://www.wikidoc.org/index.php/Braxy | |
d1b9c6409f3f10705946e200a5a87ae239647bec | wikidoc | Brine | Brine
Brine is water saturated or nearly saturated with salt (NaCl). It is used (now less popular than historically) to preserve vegetables, fish, and meat. Brine is also commonly used to age Halloumi and Feta cheeses. Although brine is used in preservation much like sugar or vinegar, it can be used to great effect in transportation. Brine is a common fluid used in the transport of heat from place to place. It is used because the addition of salt to water lowers the freezing temperature of the solution and the heat transport efficiency can be greatly enhanced for the comparatively low cost of the material. At a concentration of 23.3%, the freezing point of the solution is lowered to -21°C (252.15 K, -6°F).
At 15.5 °C (288.65 K, 60 °F) saturated brine is 26.4% salt by weight (100 degree SAL). At 0 °C (273.15 K, 32 °F) brine can only hold 23.3% salt.
# Other uses
Brine is used to pre-treat roads for winter storms. The solution is poured onto the roadways along with actual salt pellets to create a safer roadway (lowering the freezing point of the surface water, causing snow and ice to melt in higher temperature) when winter weather is in the forecast.
Brine is used in removing heat from ice surfaces such as hockey or figure skating rinks. The brine is cycled through the refrigeration plant and returned under the slab of ice at a colder temperature. Brine is used in cruise vessels' cooling systems.
Brine is used as quenching medium for cooling ferrous metals.
In Europe, brine baths are sometimes used medicinally for curing a variety of ailments from skin conditions to bladder trouble.
Brine is used in the offshore oil and gas industry where a pipeline, prior to commissioning, is flooded with a meg/brine mix to prevent the formation of hydrates on production start-up. This is dependent on the well properties.
Brine can be used for underground mining in the Arctic where the ground is permanently frozen (permafrost) in order to use water-fed drills without having them freeze. Chilled brine has also been used for localised freezing of the water table to allow mine shafts to be sunk without the risk of flooding.
Brine is commonly used to dry organic solvents after an aqueous wash. The brine wash is intended to remove the majority of the water from the organic solvent and the remainder is removed by chemical methods (typically anhydrous magnesium sulfate).
Brine is electrolyzed in the chloralkali process to make sodium hydroxide, chlorine and hydrogen, as well as the hypochlorite and chlorate salts on an industrial scale. In this case, the chloride ions are oxidized to chlorine, while water is reduced to hydrogen gas and hydroxide anions, which, together with the sodium ions already present, give sodium hydroxide on evaporation.
By adjusting the conditions, the chlorine gas produced also reacts with the hydroxide anions to give hypochlorite and chlorate anions as well.
It is also used in the Solvay process to produce sodium carbonate, and in the solution mining of salt from underground deposits. Brines are also used in the pharmaceutical industry.
When used for industrial purpose, brine is generally transported by pipeline made with welded steel pipes, coated for corrosion protection. | Brine
Brine is water saturated or nearly saturated with salt (NaCl). It is used (now less popular than historically) to preserve vegetables, fish, and meat. Brine is also commonly used to age Halloumi and Feta cheeses. Although brine is used in preservation much like sugar or vinegar, it can be used to great effect in transportation. Brine is a common fluid used in the transport of heat from place to place. It is used because the addition of salt to water lowers the freezing temperature of the solution and the heat transport efficiency can be greatly enhanced for the comparatively low cost of the material. At a concentration of 23.3%, the freezing point of the solution is lowered to -21°C (252.15 K, -6°F).
At 15.5 °C (288.65 K, 60 °F) saturated brine is 26.4% salt by weight (100 degree SAL). At 0 °C (273.15 K, 32 °F) brine can only hold 23.3% salt.
# Other uses
Brine is used to pre-treat roads for winter storms. The solution is poured onto the roadways along with actual salt pellets to create a safer roadway (lowering the freezing point of the surface water, causing snow and ice to melt in higher temperature) when winter weather is in the forecast.
Brine is used in removing heat from ice surfaces such as hockey or figure skating rinks. The brine is cycled through the refrigeration plant and returned under the slab of ice at a colder temperature. Brine is used in cruise vessels' cooling systems.
Brine is used as quenching medium for cooling ferrous metals.
In Europe, brine baths are sometimes used medicinally for curing a variety of ailments from skin conditions to bladder trouble.
Brine is used in the offshore oil and gas industry where a pipeline, prior to commissioning, is flooded with a meg/brine mix to prevent the formation of hydrates on production start-up. This is dependent on the well properties.
Brine can be used for underground mining in the Arctic where the ground is permanently frozen (permafrost) in order to use water-fed drills without having them freeze. Chilled brine has also been used for localised freezing of the water table to allow mine shafts to be sunk without the risk of flooding.
Brine is commonly used to dry organic solvents after an aqueous wash. The brine wash is intended to remove the majority of the water from the organic solvent and the remainder is removed by chemical methods (typically anhydrous magnesium sulfate).
Brine is electrolyzed in the chloralkali process to make sodium hydroxide, chlorine and hydrogen, as well as the hypochlorite and chlorate salts on an industrial scale. In this case, the chloride ions are oxidized to chlorine, while water is reduced to hydrogen gas and hydroxide anions, which, together with the sodium ions already present, give sodium hydroxide on evaporation.
By adjusting the conditions, the chlorine gas produced also reacts with the hydroxide anions to give hypochlorite and chlorate anions as well.
It is also used in the Solvay process to produce sodium carbonate, and in the solution mining of salt from underground deposits. Brines are also used in the pharmaceutical industry.
When used for industrial purpose, brine is generally transported by pipeline made with welded steel pipes, coated for corrosion protection. | https://www.wikidoc.org/index.php/Brine | |
5f69bfa6b77fc1a5ce036c91e560f07d94338bbe | wikidoc | Tosyl | Tosyl
A tosyl group (abbreviated Ts or Tos) combines the toluene and sulfonyl functional groups. The sulfonyl group consists of a hexavalent sulfur atom double bonded to two oxygen atoms and, in the tosylate group, an aromatic ring; an alkyl substituent on the R group forms a sulfonate ester. Thus, the tosylate group is the ester of toluenesulfonic acid. The para orientation illustrated (p-toluenesulfonyl) is most common, and by convention tosyl refers to the p-toluenesulfonate ester.
A tosylate ester has only a limited shelf life if it is stored outside of a desiccator as the free tosyl is readily hydrolysed by water in the presence of light. The tosyl group is electron-withdrawing. Hence, it is an excellent leaving group.
The tosyl group is also a protecting group for alcohols, prepared by combining the alcohol with toluenesulfonyl chloride in an aprotic solvent. Toluenesulfonyl chlorides activate alcohols for nucleophilic attack or elimination (dehydration).
Similarly, the brosyl (Bs) group or brosylate is a p-bromobenzenesulfonyl group with the methyl group of toluene replaced by a bromine atom. Nosyl groups in Nosylates (Ns) are 4-nitrobenzenesulfonyl groups with a nitro group in the para position.
# Applications
The use of these functional groups is examplified in an organic synthesis of the drug tolterodine, where in one of the steps a phenol group is blocked as a tosyl group and the primary alcohol as a nosyl group. The latter is a leaving group for displacement by diisopropylamine : | Tosyl
A tosyl group (abbreviated Ts or Tos) combines the toluene and sulfonyl functional groups. The sulfonyl group consists of a hexavalent sulfur atom double bonded to two oxygen atoms and, in the tosylate group, an aromatic ring; an alkyl substituent on the R group forms a sulfonate ester. Thus, the tosylate group is the ester of toluenesulfonic acid. The para orientation illustrated (p-toluenesulfonyl) is most common, and by convention tosyl refers to the p-toluenesulfonate ester.
A tosylate ester has only a limited shelf life if it is stored outside of a desiccator as the free tosyl is readily hydrolysed by water in the presence of light. The tosyl group is electron-withdrawing. Hence, it is an excellent leaving group.
The tosyl group is also a protecting group for alcohols, prepared by combining the alcohol with toluenesulfonyl chloride in an aprotic solvent. Toluenesulfonyl chlorides activate alcohols for nucleophilic attack or elimination (dehydration).
Similarly, the brosyl (Bs) group or brosylate is a p-bromobenzenesulfonyl group with the methyl group of toluene replaced by a bromine atom. Nosyl groups in Nosylates (Ns) are 4-nitrobenzenesulfonyl groups with a nitro group in the para position.
# Applications
The use of these functional groups is examplified in an organic synthesis of the drug tolterodine, where in one of the steps a phenol group is blocked as a tosyl group and the primary alcohol as a nosyl group. The latter is a leaving group for displacement by diisopropylamine [1][2]: | https://www.wikidoc.org/index.php/Brosylate | |
fa22f4824bf4f4f020e72569fd8a2041ba959e3d | wikidoc | Brpf1 | Brpf1
Peregrin also known as bromodomain and PHD finger-containing protein 1 is a protein that in humans is encoded by the BRPF1 gene located on 3p26-p25. Peregrin is a multivalent chromatin regulator that recognizes different epigenetic marks and activates three histone acetyltransferases (Moz, Morf and Hbo1). BRPF1 contains two PHD fingers, one bromodomain and one chromo/Tudor-related Pro-Trp-Trp-Pro (PWWP) domain.
# Function
## Embryo development
Brpf1 gene is very conserved and has a critical role in different developmental processes. Zebrafish BRPF1, which is coordinated by its particular set of PWWP domains, mediates Moz -dependent histone acetylation and maintains Hox genes expression throughout vertebrate development, hence determines the proper pharyngeal segmental identities. Furthermore, Brpf1 may not only has significant role for maintaining the anterior-posterior axis of the craniofacial skeleton, but also the dorsal-ventral axis of the caudal skeleton. Recent studies have shown that ablation of the mouse Brpf1 gene causes embryonic lethality at embryonic day 9.5. Specifically, Brpf1 regulates placenta vascular formation, neural tube closure, primitive hematopoiesis and embryonic fibroblast proliferation.
For the central nervous system, Brpf1 has high expression and is essential for the development of several important structures, including neocortex and dentate gyrus in the hippocampus. Brpf1 is dynamically expressed during forebrain development, especially the hippocampal neurogenesis. Brpf1 shares phenotypes with transcription factors Sox2, Tlx and Tbr2 in dentate gyrus development and has potential link to neural stem cells and progenitors. Except for the forebrain, Brpf1 is also required for the proper patterning of the craniofacial cartilage, which is derived from neural crest cells that migrate from the hindbrain.
## Cancer development
Recently, Brpf1 was reported to play the tumor suppressor or oncogenic role in several malignant tumors, including leukemia, medulloblastoma and endometrial stromal sarcoma. Brpf1 was considered a tumor suppressor gene because mutations in cancer cells appear to diminish the function of Brpf1 However, oncogenic role of Brpf1 is also possible in cancer. For example, Brpf1 can form a stable complex with Moz-Tif2, which could lead to the development of human acute myeloid leukemia (AML). There is another Brpf1 related complex Brpf1–Ing5–Eaf6, which also plays a direct role in cancer. | Brpf1
Peregrin also known as bromodomain and PHD finger-containing protein 1 is a protein that in humans is encoded by the BRPF1 gene located on 3p26-p25. Peregrin is a multivalent chromatin regulator that recognizes different epigenetic marks and activates three histone acetyltransferases (Moz, Morf and Hbo1). BRPF1 contains two PHD fingers, one bromodomain and one chromo/Tudor-related Pro-Trp-Trp-Pro (PWWP) domain.
# Function
## Embryo development
Brpf1 gene is very conserved and has a critical role in different developmental processes.[1][2][3] Zebrafish BRPF1, which is coordinated by its particular set of PWWP domains, mediates Moz -dependent histone acetylation and maintains Hox genes expression throughout vertebrate development, hence determines the proper pharyngeal segmental identities.[5] Furthermore, Brpf1 may not only has significant role for maintaining the anterior-posterior axis of the craniofacial skeleton, but also the dorsal-ventral axis of the caudal skeleton.[6] Recent studies have shown that ablation of the mouse Brpf1 gene causes embryonic lethality at embryonic day 9.5.[2][3] Specifically, Brpf1 regulates placenta vascular formation, neural tube closure, primitive hematopoiesis and embryonic fibroblast proliferation.[2][3]
For the central nervous system, Brpf1 has high expression and is essential for the development of several important structures, including neocortex and dentate gyrus in the hippocampus.[2] Brpf1 is dynamically expressed during forebrain development, especially the hippocampal neurogenesis.[4] Brpf1 shares phenotypes with transcription factors Sox2, Tlx and Tbr2 in dentate gyrus development and has potential link to neural stem cells and progenitors.[4] Except for the forebrain, Brpf1 is also required for the proper patterning of the craniofacial cartilage, which is derived from neural crest cells that migrate from the hindbrain.[7]
## Cancer development
Recently, Brpf1 was reported to play the tumor suppressor or oncogenic role in several malignant tumors, including leukemia, medulloblastoma and endometrial stromal sarcoma.[1][8][9][10] Brpf1 was considered a tumor suppressor gene because mutations in cancer cells appear to diminish the function of Brpf1[8][9] However, oncogenic role of Brpf1 is also possible in cancer. For example, Brpf1 can form a stable complex with Moz-Tif2, which could lead to the development of human acute myeloid leukemia (AML).[10] There is another Brpf1 related complex Brpf1–Ing5–Eaf6, which also plays a direct role in cancer.[1] | https://www.wikidoc.org/index.php/Brpf1 | |
badc9d8c5c009b30ee3f7f41b1ac1c65fd0150b1 | wikidoc | Bruit | Bruit
Bruit (pronounced (IPA) either Template:IPA or Template:IPA) is the term for the unusual sound that blood makes when it rushes past an obstruction (called turbulent flow) in an artery when the sound is auscultated with the bell portion of a stethoscope.
Further discussion about arterial bruits can be found here.
The location of the stethoscope when the sound is heard can guide the diagnosis:
- If the sound is heard in the neck arteries it is called a carotid bruit
- If the sound is heard in the abdomen, it is called an abdominal bruit
CME Category::Cardiology | Bruit
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Bruit (pronounced (IPA) either Template:IPA or Template:IPA) is the term for the unusual sound that blood makes when it rushes past an obstruction (called turbulent flow) in an artery when the sound is auscultated with the bell portion of a stethoscope.
Further discussion about arterial bruits can be found here.
The location of the stethoscope when the sound is heard can guide the diagnosis:
- If the sound is heard in the neck arteries it is called a carotid bruit
- If the sound is heard in the abdomen, it is called an abdominal bruit
Template:Skin and subcutaneous tissue symptoms and signs
Template:Nervous and musculoskeletal system symptoms and signs
Template:Urinary system symptoms and signs
Template:Cognition, perception, emotional state and behaviour symptoms and signs
Template:Speech and voice symptoms and signs
Template:General symptoms and signs
Template:WH
Template:WS
CME Category::Cardiology | https://www.wikidoc.org/index.php/Bruit | |
bb8fdd90f23ff67fa393d1ba3eaa42c4faf6b5db | wikidoc | Mouth | Mouth
The human mouth (or oral cavity) is covered by an upper and lower lip.
The mouth starts digestion by physically chewing the food and breaking it down with saliva.
The average male mouth holds a volume of about 100mL.
# Function
They play an important role in speech (it is part of the vocal apparatus), facial expression, kissing, eating, drinking (especially with a straw), breathing, and smoking.
Infants are born with a sucking reflex, by which they instinctively know to suck for nourishment using their lips and jaw.
# Cultural aspects
According to general etiquette, the mouth is kept closed, especially when chewing.
Lips are often adorned with lipstick or lip gloss although in most human cultures this is an affectation for females only.
Piercings have been made popular by the younger generations. Lip, tongue, and the 'Monroe' (Monroe piercing is a stud piercing placed on one's face in the same area as Marilyn Monroe's well known and prominent birthmark was) are piercings seen in many varieties. Piercings of any sort besides two subtle earrings are seen as rebellious to the norm in many western cultures.
# Development
The philtrum is the vertical groove in the upper lip, formed where the nasomedial and maxillary processes meet during embryo development. When these processes fail to fuse fully, a hare lip and/or cleft palate can result.
The nasolabial folds are the deep creases of tissue that extend from the nose to the sides of the mouth. One of the first signs of age on the human face is the increase in prominence of the nasolabial folds. | Mouth
Template:Infobox Anatomy
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
The human mouth (or oral cavity) is covered by an upper and lower lip.
The mouth starts digestion by physically chewing the food and breaking it down with saliva.
The average male mouth holds a volume of about 100mL.
# Function
They play an important role in speech (it is part of the vocal apparatus), facial expression, kissing, eating, drinking (especially with a straw), breathing, and smoking.
Infants are born with a sucking reflex, by which they instinctively know to suck for nourishment using their lips and jaw.
# Cultural aspects
According to general etiquette, the mouth is kept closed, especially when chewing.
Lips are often adorned with lipstick or lip gloss although in most human cultures this is an affectation for females only.
Piercings have been made popular by the younger generations. Lip, tongue, and the 'Monroe' (Monroe piercing is a stud piercing placed on one's face in the same area as Marilyn Monroe's well known and prominent birthmark was) are piercings seen in many varieties. Piercings of any sort besides two subtle earrings are seen as rebellious to the norm in many western cultures.
# Development
The philtrum is the vertical groove in the upper lip, formed where the nasomedial and maxillary processes meet during embryo development. When these processes fail to fuse fully, a hare lip and/or cleft palate can result.
The nasolabial folds are the deep creases of tissue that extend from the nose to the sides of the mouth. One of the first signs of age on the human face is the increase in prominence of the nasolabial folds. | https://www.wikidoc.org/index.php/Buccal_cavity | |
c71be04a12def1d5da430260f5061e2f75144ee0 | wikidoc | Butyl | Butyl
In organic chemistry, butyl is a four-carbon alkyl substituent with chemical formula -C4H9 . It is derived from either of the two isomers of the alkane called butane.
Each of the two isomers of butane give rise to two isomers of the butyl substituent. Thus, n-butane can connect at either the terminal or an internal carbon atoms, giving rise to "n-butyl" and "sec-butyl" substituents.
- n-butyl group; CH3CH2CH2CH2–, (fully systematic name "butyl")
- sec-butyl group; CH3CH2(CH3)CH–, (fully systematic name "1-methylpropyl")
The second, branched isomer of butane, isobutane can also connect either terminal methyl or internal carbon atoms, giving rise to "isobutyl" and "tertiary butyl" substituents, respectively.
- isobutyl group; (CH3)2CHCH2–, (fully systematic name "2-methylpropyl")
- tert-butyl group; (CH3)3C–, (fully systematic name "1,1-dimethylethyl")
# Nomenclature
According to IUPAC nomenclature, "isobutyl", "sec-butyl", and "tert-butyl" are all retained trivial names.
Butyl is the largest substituent for which trivial names are commonly used for all isomers.
The prefixes iso, sec and tert refer to the number of carbons connected to the primary carbon (also known as RI ("R prime"), the carbon that is connected to R). Iso means one, sec- means two and tert- means three.
# Some examples
The following are the four isomers of "butyl acetate":
# Etymology
As the number of carbons in an alkyl chain increases, butyl is the last to be named historically instead of through Greek numbers. The name is derived from butyric acid, a four carbon carboxylic acid found in rancid butter. The name of butyric acid, in turn, comes from Latin butyrum, "butter".
# Tert-butyl effect
The tert-butyl substituent is very bulky and used in chemistry for kinetic stabilisation together with other bulky groups such as the related trimethylsilyl group. The effect that the t-butyl group exerts on the progress of a chemical reaction is called the tert-butyl effect.
This effect is illustrated in the Diels-Alder reaction below where the tert-butyl substituent causes a reaction rate acceleration by a factor of 240 compared to hydrogen as the substituent. | Butyl
In organic chemistry, butyl is a four-carbon alkyl substituent with chemical formula -C4H9 . It is derived from either of the two isomers of the alkane called butane.
Each of the two isomers of butane give rise to two isomers of the butyl substituent. Thus, n-butane can connect at either the terminal or an internal carbon atoms, giving rise to "n-butyl" and "sec-butyl" substituents.
- n-butyl group; CH3CH2CH2CH2–, (fully systematic name "butyl")
- sec-butyl group; CH3CH2(CH3)CH–, (fully systematic name "1-methylpropyl")
The second, branched isomer of butane, isobutane can also connect either terminal methyl or internal carbon atoms, giving rise to "isobutyl" and "tertiary butyl" substituents, respectively.
- isobutyl group; (CH3)2CHCH2–, (fully systematic name "2-methylpropyl")
- tert-butyl group; (CH3)3C–, (fully systematic name "1,1-dimethylethyl")
# Nomenclature
According to IUPAC nomenclature, "isobutyl", "sec-butyl", and "tert-butyl" are all retained trivial names.
Butyl is the largest substituent for which trivial names are commonly used for all isomers.
The prefixes iso, sec and tert refer to the number of carbons connected to the primary carbon (also known as RI ("R prime"), the carbon that is connected to R). Iso means one, sec- means two and tert- means three.
# Some examples
The following are the four isomers of "butyl acetate":
# Etymology
As the number of carbons in an alkyl chain increases, butyl is the last to be named historically instead of through Greek numbers. The name is derived from butyric acid, a four carbon carboxylic acid found in rancid butter. The name of butyric acid, in turn, comes from Latin butyrum, "butter".
# Tert-butyl effect
The tert-butyl substituent is very bulky and used in chemistry for kinetic stabilisation together with other bulky groups such as the related trimethylsilyl group. The effect that the t-butyl group exerts on the progress of a chemical reaction is called the tert-butyl effect.
This effect is illustrated in the Diels-Alder reaction below where the tert-butyl substituent causes a reaction rate acceleration by a factor of 240 compared to hydrogen as the substituent.[1] | https://www.wikidoc.org/index.php/Butyl | |
b60e16ed254c8c52ca2c3f830d5c5569b14919cc | wikidoc | c-Fos | c-Fos
In the fields of molecular biology and genetics, c-Fos is a proto-oncogene that is the human homolog of the retroviral oncogene v-fos. It was first discovered in rat fibroblasts as the transforming gene of the FBJ MSV (Finkel–Biskis–Jinkins murine osteogenic sarcoma virus) (Curran and Tech, 1982). It is a part of a bigger Fos family of transcription factors which includes c-Fos, FosB, Fra-1 and Fra-2. It has been mapped to chromosome region 14q21→q31. c-Fos encodes a 62 kDa protein, which forms heterodimer with c-jun (part of Jun family of transcription factors), resulting in the formation of AP-1 (Activator Protein-1) complex which binds DNA at AP-1 specific sites at the promoter and enhancer regions of target genes and converts extracellular signals into changes of gene expression. It plays an important role in many cellular functions and has been found to be overexpressed in a variety of cancers.
# Structure and function
c-fos is a 380 amino acid protein with a basic leucine zipper region for dimerisation and DNA-binding and a transactivation domain at C-terminus. Unlike Jun proteins, it cannot form homodimers, only heterodimers with c-jun. In vitro studies have shown that Jun–Fos heterodimers are more stable and have stronger DNA-binding activity than Jun–Jun homodimers.
A variety of stimuli, including serum, growth factors, tumor promoters, cytokines, and UV radiation induce their expression. The c-fos mRNA and protein is generally among the first to be expressed and hence referred to as an immediate early gene. It is rapidly and transiently induced, within 15 minutes of stimulation. Its activity is also regulated by posttranslational modification caused by phosphorylation by different kinases, like MAPK, cdc2, PKA or PKC which influence protein stability, DNA-binding activity and the trans-activating potential of the transcription factors. It can cause gene repression as well as gene activation, although different domains are believed to be involved in both processes.
It is involved in important cellular events, including cell proliferation, differentiation and survival; genes associated with hypoxia; and angiogenesis; which makes its dysregulation an important factor for cancer development. It can also induce a loss of cell polarity and epithelial-mesenchymal transition, leading to invasive and metastatic growth in mammary epithelial cells.
The importance of c-fos in biological context has been determined by eliminating endogenous function by using anti-sense mRNA, anti-c-fos antibodies, a ribozyme that cleaves c-fos mRNA or a dominant negative mutant of c-fos. The transgenic mice thus generated are viable, demonstrating that there are c-fos dependent and independent pathways of cell proliferation, but display a range of tissue-specific developmental defects, including osteoporosis, delayed gametogenesis, lymphopenia and behavioral abnormalities.
# Clinical significance
The AP-1 complex has been implicated in transformation and progression of cancer. In osteosarcoma and endometrial carcinoma, c-Fos overexpression was associated with high-grade lesions and poor prognosis. Also, in a comparison between precancerous lesion of the cervix uteri and invasive cervical cancer, c-Fos expression was significantly lower in precancerous lesions. c-Fos has also been identified as independent predictor of decreased survival in breast cancer.
It was found that overexpression of c-fos from class I MHC promoter in transgenic mice leads to the formation of osteosarcomas due to increased proliferation of osteoblasts whereas ectopic expression of the other Jun and Fos proteins does not induce any malignant tumors. Activation of the c-Fos transgene in mice results in overexpression of cyclin D1, A and E in osteoblasts and chondrocytes, both in vitro and in vivo, which might contribute to the uncontrolled growth leading to tumor. Human osteosarcomas analyzed for c-fos expression have given positive results in more than half the cases and c-fos expression has been associated with higher frequency of relapse and poor response to chemotherapy.
Several studies have raised the idea that c-Fos may also have tumor-suppressor activity, that it might be able to promote as well as suppress tumorigenesis. Supporting this is the observation that in ovarian carcinomas, loss of c-Fos expression correlates with disease progression. This double action could be enabled by differential protein composition of tumour cells and their environment, for example, dimerisation partners, co-activators and promoter architecture. It is possible that the tumor suppressing activity is due to a proapoptotic function. The exact mechanism by which c-Fos contributes to apoptosis is not clearly understood, but observations in human hepatocellular carcinoma cells indicate that c-Fos is a mediator of c-myc-induced cell death and might induce apoptosis through the p38 MAP kinase pathway. Fas ligand (FASLG or FasL) and the tumour necrosis factor-related apoptosis-inducing ligand (TNFSF10 or TRAIL) might reflect an additional apoptotic mechanism induced by c-Fos, as observed in a human T-cell leukaemia cell line. Another possible mechanism of c-Fos involvement in tumour suppression could be the direct regulation of BRCA1, a well established factor in familial breast and ovarian cancer.
In addition, the role of c-fos and other Fos family proteins has also been studied in endometrial carcinoma, cervical cancer, mesotheliomas, colorectal cancer, lung cancer, melanomas, thyroid carcinomas, esophageal cancer, hepatocellular carcinomas, etc.
Cocaine, methamphetamine, heroin, and other psychoactive drugs have been shown to increase c-fos production in the mesocortical pathway (prefrontal cortex) as well as in the mesolimbic reward pathway (nucleus accumbens). c-Fos repression by ΔFosB's AP-1 complex within the D1-type medium spiny neurons of the nucleus accumbens acts as a molecular switch that enables the chronic induction of ΔFosB, thus allowing it to accumulate more rapidly. As such, the c-Fos promoter finds utilization in drug addiction research in general, as well as with context-induced relapse to drug-seeking and other behavioral changes associated with chronic drug taking.
An increase in c-Fos production in androgen receptor-containing neurons has been observed in rats after mating.
# Applications
Expression of c-fos is an indirect marker of neuronal activity because c-fos is often expressed when neurons fire action potentials. Upregulation of c-fos mRNA in a neuron indicates recent activity.
The c-fos promoter has also been utilised for drug abuse research. Scientists use this promoter to turn on transgenes in rats, allowing them to manipulate specific neuronal ensembles to assess their role in drug-related memories and behavior. This neuronal control can be replicated with optogenetics or DREADDs
# Interactions
c-Fos has been shown to interact with:
- BCL3,
- COBRA1,
- CSNK2A1,
- CSNK2A2,
- DDIT3,
- JUN
- NCOA1;,
- NCOR2,
- RELA,
- RUNX1,
- RUNX2,
- SMAD3, and
- TBP. | c-Fos
In the fields of molecular biology and genetics, c-Fos is a proto-oncogene that is the human homolog of the retroviral oncogene v-fos.[1] It was first discovered in rat fibroblasts as the transforming gene of the FBJ MSV (Finkel–Biskis–Jinkins murine osteogenic sarcoma virus) (Curran and Tech, 1982). It is a part of a bigger Fos family of transcription factors which includes c-Fos, FosB, Fra-1 and Fra-2.[2] It has been mapped to chromosome region 14q21→q31. c-Fos encodes a 62 kDa protein, which forms heterodimer with c-jun (part of Jun family of transcription factors), resulting in the formation of AP-1 (Activator Protein-1) complex which binds DNA at AP-1 specific sites at the promoter and enhancer regions of target genes and converts extracellular signals into changes of gene expression.[3] It plays an important role in many cellular functions and has been found to be overexpressed in a variety of cancers.
# Structure and function
c-fos is a 380 amino acid protein with a basic leucine zipper region for dimerisation and DNA-binding and a transactivation domain at C-terminus. Unlike Jun proteins, it cannot form homodimers, only heterodimers with c-jun. In vitro studies have shown that Jun–Fos heterodimers are more stable and have stronger DNA-binding activity than Jun–Jun homodimers.[4]
A variety of stimuli, including serum, growth factors, tumor promoters, cytokines, and UV radiation induce their expression. The c-fos mRNA and protein is generally among the first to be expressed and hence referred to as an immediate early gene. It is rapidly and transiently induced, within 15 minutes of stimulation.[5] Its activity is also regulated by posttranslational modification caused by phosphorylation by different kinases, like MAPK, cdc2, PKA or PKC which influence protein stability, DNA-binding activity and the trans-activating potential of the transcription factors.[6][7][8] It can cause gene repression as well as gene activation, although different domains are believed to be involved in both processes.
It is involved in important cellular events, including cell proliferation, differentiation and survival; genes associated with hypoxia; and angiogenesis;[9] which makes its dysregulation an important factor for cancer development. It can also induce a loss of cell polarity and epithelial-mesenchymal transition, leading to invasive and metastatic growth in mammary epithelial cells.[10]
The importance of c-fos in biological context has been determined by eliminating endogenous function by using anti-sense mRNA, anti-c-fos antibodies, a ribozyme that cleaves c-fos mRNA or a dominant negative mutant of c-fos. The transgenic mice thus generated are viable, demonstrating that there are c-fos dependent and independent pathways of cell proliferation, but display a range of tissue-specific developmental defects, including osteoporosis, delayed gametogenesis, lymphopenia and behavioral abnormalities.
# Clinical significance
The AP-1 complex has been implicated in transformation and progression of cancer. In osteosarcoma and endometrial carcinoma, c-Fos overexpression was associated with high-grade lesions and poor prognosis. Also, in a comparison between precancerous lesion of the cervix uteri and invasive cervical cancer, c-Fos expression was significantly lower in precancerous lesions. c-Fos has also been identified as independent predictor of decreased survival in breast cancer.[18]
It was found that overexpression of c-fos from class I MHC promoter in transgenic mice leads to the formation of osteosarcomas due to increased proliferation of osteoblasts whereas ectopic expression of the other Jun and Fos proteins does not induce any malignant tumors. Activation of the c-Fos transgene in mice results in overexpression of cyclin D1, A and E in osteoblasts and chondrocytes, both in vitro and in vivo, which might contribute to the uncontrolled growth leading to tumor. Human osteosarcomas analyzed for c-fos expression have given positive results in more than half the cases and c-fos expression has been associated with higher frequency of relapse and poor response to chemotherapy.
Several studies have raised the idea that c-Fos may also have tumor-suppressor activity, that it might be able to promote as well as suppress tumorigenesis. Supporting this is the observation that in ovarian carcinomas, loss of c-Fos expression correlates with disease progression. This double action could be enabled by differential protein composition of tumour cells and their environment, for example, dimerisation partners, co-activators and promoter architecture. It is possible that the tumor suppressing activity is due to a proapoptotic function. The exact mechanism by which c-Fos contributes to apoptosis is not clearly understood, but observations in human hepatocellular carcinoma cells indicate that c-Fos is a mediator of c-myc-induced cell death and might induce apoptosis through the p38 MAP kinase pathway. Fas ligand (FASLG or FasL) and the tumour necrosis factor-related apoptosis-inducing ligand (TNFSF10 or TRAIL) might reflect an additional apoptotic mechanism induced by c-Fos, as observed in a human T-cell leukaemia cell line. Another possible mechanism of c-Fos involvement in tumour suppression could be the direct regulation of BRCA1, a well established factor in familial breast and ovarian cancer.
In addition, the role of c-fos and other Fos family proteins has also been studied in endometrial carcinoma, cervical cancer, mesotheliomas, colorectal cancer, lung cancer, melanomas, thyroid carcinomas, esophageal cancer, hepatocellular carcinomas, etc.
Cocaine, methamphetamine,[19] heroin,[20] and other psychoactive drugs[21][22] have been shown to increase c-fos production in the mesocortical pathway (prefrontal cortex) as well as in the mesolimbic reward pathway (nucleus accumbens). c-Fos repression by ΔFosB's AP-1 complex within the D1-type medium spiny neurons of the nucleus accumbens acts as a molecular switch that enables the chronic induction of ΔFosB, thus allowing it to accumulate more rapidly. As such, the c-Fos promoter finds utilization in drug addiction research in general, as well as with context-induced relapse to drug-seeking and other behavioral changes associated with chronic drug taking.
An increase in c-Fos production in androgen receptor-containing neurons has been observed in rats after mating.
# Applications
Expression of c-fos is an indirect marker of neuronal activity because c-fos is often expressed when neurons fire action potentials.[23][24] Upregulation of c-fos mRNA in a neuron indicates recent activity.[25]
The c-fos promoter has also been utilised for drug abuse research. Scientists use this promoter to turn on transgenes in rats, allowing them to manipulate specific neuronal ensembles to assess their role in drug-related memories and behavior.[26] This neuronal control can be replicated with optogenetics or DREADDs [27]
# Interactions
c-Fos has been shown to interact with:
- BCL3,[28]
- COBRA1,[29]
- CSNK2A1,[30]
- CSNK2A2,[30]
- DDIT3,[31]
- JUN[32][33][34][35][36][37][38]
- NCOA1;,[39][40]
- NCOR2,[41]
- RELA,[32]
- RUNX1,[42][43]
- RUNX2,[42][43]
- SMAD3,[44] and
- TBP.[45] | https://www.wikidoc.org/index.php/C-Fos | |
37302a225eab591ad5e2be3f2cdf609cfd688366 | wikidoc | c-jun | c-jun
c-Jun is a protein that in humans is encoded by the JUN gene. c-Jun, in combination with c-Fos, forms the AP-1 early response transcription factor. It was first identified as the Fos-binding protein p39 and only later rediscovered as the product of the c-jun gene. It is activated through double phosphorylation by the JNK pathway but has also a phosphorylation-independent function. c-jun knockout is lethal, but transgenic animals with a mutated c-jun that cannot be phosphorylated (termed c-junAA) can survive.
This gene is the putative transforming gene of avian sarcoma virus 17. It encodes a protein that is highly similar to the viral protein, and that interacts directly with specific target DNA sequences to regulate gene expression. This gene is intronless and is mapped to 1p32-p31, a chromosomal region involved in both translocations and deletions in human malignancies.
# Function
## Regulation
Both Jun and its dimerization partners in AP-1 formation are subject to regulation by diverse extracellular stimuli, which include peptide growth factors, pro-inflammatory cytokines, oxidative and other forms of cellular stress, and UV irradiation. For example, UV irradiation is a potent inducer for elevated c-jun expression.
The c-jun transcription is autoregulated by its own product, Jun. The binding of Jun (AP-1) to a high-affinity AP-1 binding site in the jun promoter region induces jun transcription. This positive autoregulation by stimulating its own transcription may be a mechanism for prolonging the signals from extracellular stimuli. This mechanism can have biological significance for the activity of c-jun in cancer.
Also, the c-jun activities can be regulated by the ERK pathway. Constitutively active ERK is found to increase c-jun transcription and stability through CREB and GSK3. This results in activated c-jun and its downstream targets such as RACK1 and cyclin D1. RACK1 can enhance JNK activity, and activated JNK signaling subsequently exerts regulation on c-jun activity.
Phosphorylation of Jun at serines 63 and 73 and threonine 91 and 93 increases transcription of the c-jun target genes. Therefore, regulation of c-jun activity can be achieved through N-terminal phosphorylation by the Jun N-terminal kinases (JNKs). It is shown that Jun’s activity (AP-1 activity) in stress-induced apoptosis and cellular proliferation is regulated by its N-terminal phosphorylation. Another study showed that oncogenic transformation by ras and fos also requires Jun N-terminal phosphorylation at Serine 63 and 73.
## Cell cycle progression
Studies have shown that c-jun is required for progression through the G1 phase of the cell cycle, and c-jun null cells show increased G1 arrest. C-jun regulates the transcriptional level of cyclin D1, which is a major Rb kinase. Rb is a growth suppressor, and it is inactivated by phosphorylation. Therefore, c-jun is required for maintaining sufficient cyclin D1 kinase activity and allowing cell cycle progression.
In cells absent of c-jun, the expression of p53 (cell cycle arrest inducer) and p21 (CDK inhibitor and p53 target gene) is increased, and those cells exhibit cell cycle defect. Overexpression of c-jun in cells results in decreased level of p53 and p21, and exhibits accelerated cell proliferation. C-jun represses p53 transcription by binding to a variant AP-1 site in the p53 promoter. Those results indicate that c-jun downregulates p53 to control cell cycle progression.
## Anti-apoptotic activity
UV irradiation can activate c-jun expression and the JNK signaling pathway. C-jun protects cells from UV-induced apoptosis, and it cooperates with NF-κB to prevent apoptosis induced by TNFα. The protection from apoptosis by c-jun requires serines 63/73 (involved in phosphorylation of Jun), which is not required in c-jun-mediated G1 progress. This suggests that c-jun regulates cell cycle progression and apoptosis through two separated mechanisms.
A study utilized liver-specific inactivation of c-jun in hepatocellular carcinoma, which showed impaired tumor development correlated with increased level of p53 protein and the mRNA level of the p53 target gene noxa. Also, c-jun can protect hepatocytes from apoptosis, as hepatocytes lacking c-jun showed increased sensitivity to TNFα-induced apoptosis. In those hepatocytes lacking c-jun, deletion of p53 can restore resistance toward TNFα. Those results indicate that c-jun antagonizes the proapoptotic activity of p53 in liver tumor.
# Clinical significance
It is known that c-jun plays a role in cellular proliferation and apoptosis of the endometrium throughout the menstrual cycle. The cyclic change of the c-jun protein levels is significant in the proliferation and apoptosis of glandular epithelial cells. The persistent stromal expression of c-jun protein may prevent stromal cells from entering into apoptosis during the late secretory phase.
## Cancer
C-jun is a proto-oncogene (its protein is Jun) and is the cellular homolog of the viral oncoprotein v-jun. Jun is the first discovered oncogenic transcription factor.
In a study using non-small cell lung cancers (NSCLC), c-jun was found to be overexpressed in 31% of the cases in primary and metastatic lung tumors, whereas normal conducting airway and alveolar epithelia in general did not express c-jun.
A study with a group consisted of 103 cases of phase I/II invasive breast cancers showed that activated c-jun is expressed predominantly at the invasive front of breast cancer and is associated with proliferation and angiogenesis.
## Tumor initiation
A study was done with liver-specific inactivation of c-jun at different stages of tumor development in mice with chemically induced hepatocellular carcinomas. The result indicates that c-jun is required at the early stage of tumor development, and deletion of c-jun can largely suppress tumor formation. Also, c-jun is required for tumor cell survival between the initiation and progression stages. In contrast to that, inactivation of c-jun in advanced tumors does not impair tumor progression.
## Breast cancer
Overexpression of c-jun in MCF-7 cells can result in overall increased aggressiveness, as shown by increased cellular motility, increased expression of a matrix-degrading enzyme MMP-9, increased in vitro chemoinvasion, and tumor formation in nude mice in the absence of exogenous estrogens. The MCF-7 cells with c-jun overexpression became unresponsive to estrogen and tamoxifen, thus c-jun overexpression is proposed to lead to an estrogen-independent phenotype in breast cancer cells. The observed phenotype for MCF-7 cells with c-jun overexpression is similar to that observed clinically in advanced breast cancer, which had become hormone unresponsive.
The invasive phenotype contributed by c-jun overexpression is confirmed in another study. In addition, this study showed increased in vivo liver metastasis by the breast cancer with c-jun overexpression. This finding suggests that c-jun plays a critical role in the metastasis of breast cancer.
In mammary tumors, endogenous c-jun was found to play a key role in ErbB2-induced migration and invasion of mammary epithelial cells. Jun transcriptionally activates the promoters of SCF (stem cell factor) and CCL5. The induced SCF and CCL5 expression promotes a self-renewing mammary epithelial population. It suggests that c-jun mediates the expansion of breast cancer stem cells to enhance tumor invasiveness.
## Cellular differentiation
Ten undifferentiated and highly aggressive sarcomas showed amplification of the jun gene and JUN overexpression at both RNA and protein levels. Overexpression of c-jun in 3T3-L1 cells (a preadipocytic non-tumoral cell line that resembles human liposarcoma) can block or delay adipocytic differentiation of those cells.
## Nerve and Spinal Cord Regeneration
Peripheral nerve injury in rodents rapidly activates JNK signaling which in turn activates c-Jun. In contrast, nerve injury in the central nervous system does not. c-Jun is sufficient to promote axon regeneration in both the peripheral and central nervous systems as overexpression in both dorsal root ganglion neurons and cortical neurons leads to increased regeneration.
# As anti-cancer drug target
A study showed that oncogenic transformation by ras and fos requires Jun N-terminal phosphorylation at Serine 63 and 73 by the Jun N- terminal kinases (JNK). In this study, the induced skin tumor and osteosarcoma showed impaired development in mice with a mutant Jun incapable of N-terminal phosphorylation. Also, in a mouse model of intestinal cancer, genetic abrogation of Jun N-terminal phosphorylation or gut-specific c-jun inactivation attenuated cancer development and prolonged lifespan. Therefore, targeting the N-terminal phosphorylation of Jun (or the JNK signaling pathway) can be a potential strategy for inhibiting tumor growth.
In melanoma-derived B16-F10 cancer cells, c-jun inactivation by a pharmacological JNK/jun inhibitor SP combined with JunB knockdown can result in cytotoxic effect, leading to cell arrest and apoptosis. This anti-JunB /Jun strategy can increase the survival of mice inoculated with tumor cells, which suggests a potential antitumor strategy through Jun and JunB inhibition.
# Anti-cancer property of c-jun
Most research results show that c-jun contributes to tumor initiation and increased invasiveness. However, a few studies discovered some alternative activities of c-jun, suggesting that c-jun may actually be a double-edge sword in cancer.
## p16INK4a
p16INK4a is a tumor suppressor and a cell cycle inhibitor, and a study shows that c-jun acts as “bodyguard” to p16INK4a by preventing methylation of the p16INK4a promoter. Therefore, c-jun can prevent silencing of the gene p16INK4a.
## Tylophorine
Tylophorine is a type of plant-derived alkaloid with anticancer activity by inducing cell cycle arrest. A study demonstrated that tylophorine treatment increased c-jun protein accumulation. Then c-jun expression in conjunction with tylophorine promotes G1 arrest in carcinoma cells through the downregulation of cyclin A2. Therefore, the result indicates that the anticancer mechanism of tylophorine is mediated through c-jun.
# Interactions
C-jun has been shown to interact with:
- ATF2
- AR
- ASCC3
- ATF3
- BCL3
- BCL6
- BRCA1
- C-Fos
- CSNK2A1
- NELFB
- COPS5
- CREBBP
- CSNK2A2
- DDX21,
- DDIT3
- ERG
- ETS2,
- FOSL1
- TGIF1
- MAPK8
- SMAD3
- MyoD
- NACA
- NFE2L1
- NFE2L2
- NCOR2
- NCOA1
- PIN1
- RBM39
- RELA
- RB1
- RFWD2
- RUNX1
- RUNX2
- STAT1
- STAT3
- TBP and
- GTF2B. | c-jun
c-Jun is a protein that in humans is encoded by the JUN gene. c-Jun, in combination with c-Fos, forms the AP-1 early response transcription factor. It was first identified as the Fos-binding protein p39 and only later rediscovered as the product of the c-jun gene. It is activated through double phosphorylation by the JNK pathway but has also a phosphorylation-independent function. c-jun knockout is lethal, but transgenic animals with a mutated c-jun that cannot be phosphorylated (termed c-junAA) can survive.
This gene is the putative transforming gene of avian sarcoma virus 17. It encodes a protein that is highly similar to the viral protein, and that interacts directly with specific target DNA sequences to regulate gene expression. This gene is intronless and is mapped to 1p32-p31, a chromosomal region involved in both translocations and deletions in human malignancies.[1]
# Function
## Regulation
Both Jun and its dimerization partners in AP-1 formation are subject to regulation by diverse extracellular stimuli, which include peptide growth factors, pro-inflammatory cytokines, oxidative and other forms of cellular stress, and UV irradiation. For example, UV irradiation is a potent inducer for elevated c-jun expression.[2]
The c-jun transcription is autoregulated by its own product, Jun. The binding of Jun (AP-1) to a high-affinity AP-1 binding site in the jun promoter region induces jun transcription. This positive autoregulation by stimulating its own transcription may be a mechanism for prolonging the signals from extracellular stimuli. This mechanism can have biological significance for the activity of c-jun in cancer.[3]
Also, the c-jun activities can be regulated by the ERK pathway. Constitutively active ERK is found to increase c-jun transcription and stability through CREB and GSK3. This results in activated c-jun and its downstream targets such as RACK1 and cyclin D1. RACK1 can enhance JNK activity, and activated JNK signaling subsequently exerts regulation on c-jun activity.[4]
Phosphorylation of Jun at serines 63 and 73 and threonine 91 and 93 increases transcription of the c-jun target genes.[5] Therefore, regulation of c-jun activity can be achieved through N-terminal phosphorylation by the Jun N-terminal kinases (JNKs). It is shown that Jun’s activity (AP-1 activity) in stress-induced apoptosis and cellular proliferation is regulated by its N-terminal phosphorylation.[6] Another study showed that oncogenic transformation by ras and fos also requires Jun N-terminal phosphorylation at Serine 63 and 73.[7]
## Cell cycle progression
Studies have shown that c-jun is required for progression through the G1 phase of the cell cycle, and c-jun null cells show increased G1 arrest. C-jun regulates the transcriptional level of cyclin D1, which is a major Rb kinase. Rb is a growth suppressor, and it is inactivated by phosphorylation. Therefore, c-jun is required for maintaining sufficient cyclin D1 kinase activity and allowing cell cycle progression.[2]
In cells absent of c-jun, the expression of p53 (cell cycle arrest inducer) and p21 (CDK inhibitor and p53 target gene) is increased, and those cells exhibit cell cycle defect. Overexpression of c-jun in cells results in decreased level of p53 and p21, and exhibits accelerated cell proliferation. C-jun represses p53 transcription by binding to a variant AP-1 site in the p53 promoter. Those results indicate that c-jun downregulates p53 to control cell cycle progression.[8]
## Anti-apoptotic activity
UV irradiation can activate c-jun expression and the JNK signaling pathway. C-jun protects cells from UV-induced apoptosis, and it cooperates with NF-κB to prevent apoptosis induced by TNFα. The protection from apoptosis by c-jun requires serines 63/73 (involved in phosphorylation of Jun), which is not required in c-jun-mediated G1 progress. This suggests that c-jun regulates cell cycle progression and apoptosis through two separated mechanisms.[2]
A study utilized liver-specific inactivation of c-jun in hepatocellular carcinoma, which showed impaired tumor development correlated with increased level of p53 protein and the mRNA level of the p53 target gene noxa. Also, c-jun can protect hepatocytes from apoptosis, as hepatocytes lacking c-jun showed increased sensitivity to TNFα-induced apoptosis. In those hepatocytes lacking c-jun, deletion of p53 can restore resistance toward TNFα. Those results indicate that c-jun antagonizes the proapoptotic activity of p53 in liver tumor.[9]
# Clinical significance
It is known that c-jun plays a role in cellular proliferation and apoptosis of the endometrium throughout the menstrual cycle. The cyclic change of the c-jun protein levels is significant in the proliferation and apoptosis of glandular epithelial cells. The persistent stromal expression of c-jun protein may prevent stromal cells from entering into apoptosis during the late secretory phase.[10]
## Cancer
C-jun is a proto-oncogene (its protein is Jun) and is the cellular homolog of the viral oncoprotein v-jun.[2] Jun is the first discovered oncogenic transcription factor.[11]
In a study using non-small cell lung cancers (NSCLC), c-jun was found to be overexpressed in 31% of the cases in primary and metastatic lung tumors, whereas normal conducting airway and alveolar epithelia in general did not express c-jun.[12]
A study with a group consisted of 103 cases of phase I/II invasive breast cancers showed that activated c-jun is expressed predominantly at the invasive front of breast cancer and is associated with proliferation and angiogenesis.[13]
## Tumor initiation
A study was done with liver-specific inactivation of c-jun at different stages of tumor development in mice with chemically induced hepatocellular carcinomas. The result indicates that c-jun is required at the early stage of tumor development, and deletion of c-jun can largely suppress tumor formation. Also, c-jun is required for tumor cell survival between the initiation and progression stages. In contrast to that, inactivation of c-jun in advanced tumors does not impair tumor progression.[9]
## Breast cancer
Overexpression of c-jun in MCF-7 cells can result in overall increased aggressiveness, as shown by increased cellular motility, increased expression of a matrix-degrading enzyme MMP-9, increased in vitro chemoinvasion, and tumor formation in nude mice in the absence of exogenous estrogens. The MCF-7 cells with c-jun overexpression became unresponsive to estrogen and tamoxifen, thus c-jun overexpression is proposed to lead to an estrogen-independent phenotype in breast cancer cells. The observed phenotype for MCF-7 cells with c-jun overexpression is similar to that observed clinically in advanced breast cancer, which had become hormone unresponsive.[14]
The invasive phenotype contributed by c-jun overexpression is confirmed in another study. In addition, this study showed increased in vivo liver metastasis by the breast cancer with c-jun overexpression. This finding suggests that c-jun plays a critical role in the metastasis of breast cancer.[15]
In mammary tumors, endogenous c-jun was found to play a key role in ErbB2-induced migration and invasion of mammary epithelial cells. Jun transcriptionally activates the promoters of SCF (stem cell factor) and CCL5. The induced SCF and CCL5 expression promotes a self-renewing mammary epithelial population. It suggests that c-jun mediates the expansion of breast cancer stem cells to enhance tumor invasiveness.[16]
## Cellular differentiation
Ten undifferentiated and highly aggressive sarcomas showed amplification of the jun gene and JUN overexpression at both RNA and protein levels. Overexpression of c-jun in 3T3-L1 cells (a preadipocytic non-tumoral cell line that resembles human liposarcoma) can block or delay adipocytic differentiation of those cells.[17]
## Nerve and Spinal Cord Regeneration
Peripheral nerve injury in rodents rapidly activates JNK signaling which in turn activates c-Jun. In contrast, nerve injury in the central nervous system does not. c-Jun is sufficient to promote axon regeneration in both the peripheral and central nervous systems as overexpression in both dorsal root ganglion neurons and cortical neurons leads to increased regeneration. [18]
# As anti-cancer drug target
A study showed that oncogenic transformation by ras and fos requires Jun N-terminal phosphorylation at Serine 63 and 73 by the Jun N- terminal kinases (JNK). In this study, the induced skin tumor and osteosarcoma showed impaired development in mice with a mutant Jun incapable of N-terminal phosphorylation.[7] Also, in a mouse model of intestinal cancer, genetic abrogation of Jun N-terminal phosphorylation or gut-specific c-jun inactivation attenuated cancer development and prolonged lifespan.[5] Therefore, targeting the N-terminal phosphorylation of Jun (or the JNK signaling pathway) can be a potential strategy for inhibiting tumor growth.
In melanoma-derived B16-F10 cancer cells, c-jun inactivation by a pharmacological JNK/jun inhibitor SP combined with JunB knockdown can result in cytotoxic effect, leading to cell arrest and apoptosis. This anti-JunB /Jun strategy can increase the survival of mice inoculated with tumor cells, which suggests a potential antitumor strategy through Jun and JunB inhibition.[19]
# Anti-cancer property of c-jun
Most research results show that c-jun contributes to tumor initiation and increased invasiveness. However, a few studies discovered some alternative activities of c-jun, suggesting that c-jun may actually be a double-edge sword in cancer.
## p16INK4a
p16INK4a is a tumor suppressor and a cell cycle inhibitor, and a study shows that c-jun acts as “bodyguard” to p16INK4a by preventing methylation of the p16INK4a promoter. Therefore, c-jun can prevent silencing of the gene p16INK4a.[20]
## Tylophorine
Tylophorine is a type of plant-derived alkaloid with anticancer activity by inducing cell cycle arrest. A study demonstrated that tylophorine treatment increased c-jun protein accumulation. Then c-jun expression in conjunction with tylophorine promotes G1 arrest in carcinoma cells through the downregulation of cyclin A2. Therefore, the result indicates that the anticancer mechanism of tylophorine is mediated through c-jun.[21]
# Interactions
C-jun has been shown to interact with:
- ATF2[22][23][24]
- AR[25]
- ASCC3[26]
- ATF3[24][27][28]
- BCL3[29]
- BCL6[30]
- BRCA1[31]
- C-Fos[32][33][34][35][36][37][38]
- CSNK2A1[39]
- NELFB[40]
- COPS5[41]
- CREBBP[42]
- CSNK2A2[39]
- DDX21,[43]
- DDIT3[44]
- ERG[45]
- ETS2,[46]
- FOSL1[33]
- TGIF1[47]
- MAPK8[48][49][50][51][52][53][54][55]
- SMAD3[56][57][58]
- MyoD[59]
- NACA[60]
- NFE2L1[38]
- NFE2L2[38]
- NCOR2[61]
- NCOA1[62][63][64]
- PIN1[65]
- RBM39[66]
- RELA[35]
- RB1[67]
- RFWD2[68][69]
- RUNX1[70][71]
- RUNX2[70][71]
- STAT1[72]
- STAT3[72]
- TBP[73] and
- GTF2B.[73] | https://www.wikidoc.org/index.php/C-Jun | |
7e1114da9450c6d8507b85814da7548e1ecdb213 | wikidoc | CD117 | CD117
Mast/stem cell growth factor receptor (SCFR), also known as proto-oncogene c-Kit or tyrosine-protein kinase Kit or CD117, is a receptor tyrosine kinase protein that in humans is encoded by the KIT gene. Multiple transcript variants encoding different isoforms have been found for this gene.
KIT was first described by the German biochemist Axel Ullrich in 1987 as the cellular homolog of the feline sarcoma viral oncogene v-kit.
# Cell surface marker
Cluster of differentiation (CD) molecules are markers on the cell surface, as recognized by specific sets of antibodies, used to identify the cell type, stage of differentiation and activity of a cell. CD117 is an important cell surface marker used to identify certain types of hematopoietic (blood) progenitors in the bone marrow. To be specific, hematopoietic stem cells (HSC), multipotent progenitors (MPP), and common myeloid progenitors (CMP) express high levels of CD117. Common lymphoid progenitors (CLP) express low surface levels of CD117.
CD117 also identifies the earliest thymocyte progenitors in the thymus. To be specific, early T lineage progenitors (ETP/DN1) and DN2 thymocytes express high levels of c-Kit. It is also a marker for mouse prostate stem cells. In addition, mast cells, melanocytes in the skin, and interstitial cells of Cajal in the digestive tract express CD117. In humans, expression of c-kit in helper-like innate lymphoid cells (ILCs) which lack the expression of CRTH2 (CD294) is used to mark the ILC3 population.
# Function
CD117 is a cytokine receptor expressed on the surface of hematopoietic stem cells as well as other cell types. Altered forms of this receptor may be associated with some types of cancer. CD117 is a receptor tyrosine kinase type III, which binds to stem cell factor (a substance that causes certain types of cells to grow), also known as "steel factor" or "c-kit ligand". When this receptor binds to stem cell factor (SCF) it forms a dimer that activates its intrinsic tyrosine kinase activity, that in turn phosphorylates and activates signal transduction molecules that propagate the signal in the cell. Signaling through CD117 plays a role in cell survival, proliferation, and differentiation.
# Mobilization
Hematopoietic progenitor cells are normally present in the blood at low levels. Mobilization is the process by which progenitors are made to migrate from the bone marrow into the bloodstream, thus increasing their numbers in the blood. Mobilization is used clinically as a source of hematopoietic stem cells for hematopoietic stem cell transplantation (HSCT). Signaling through CD117 has been implicated in mobilization. At the current time, G-CSF is the main drug used for mobilization; it indirectly activates CD117. Plerixafor (an antagonist of CXCR4-SDF1) in combination with G-CSF, is also being used for mobilization of hematopoietic progenitor cells. Direct CD117 agonists are currently being developed as mobilization agents.
# Role in cancer
Activating mutations in this gene are associated with gastrointestinal stromal tumors, testicular seminoma, mast cell disease, melanoma, acute myeloid leukemia, while inactivating mutations are associated with the genetic defect piebaldism.
## Anti-KIT therapies
CD117 is a proto-oncogene, meaning that overexpression or mutations of this protein can lead to cancer. Seminomas, a subtype of testicular germ cell tumors, frequently have activating mutations in exon 17 of CD117. In addition, the gene encoding CD117 is frequently overexpressed and amplified in this tumor type, most commonly occurring as a single gene amplicon. Mutations of CD117 have also been implicated in leukemia, a cancer of hematopoietic progenitors, melanoma, mast cell disease, and gastrointestinal stromal tumors (GISTs). The efficacy of imatinib (trade name Gleevec), a CD117 inhibitor, is determined by the mutation status of CD117:
When the mutation has occurred in exon 11 (as is the case many times in GISTs), the tumors are responsive to imatinib. However, if the mutation occurs in exon 17 (as is often the case in seminomas and leukemias), the receptor is not inhibited by imatinib. In those cases other inhibitors such as dasatinib and nilotinib can be used. Researchers investigated the dynamic behavior of wild type and mutant D816H KIT receptor, and emphasized the extended A-loop (EAL) region (805-850) by conducting computational analysis. Their atomic investigation of mutant KIT receptor which emphasized on the EAL region provided a better insight into the understanding of the sunitinib resistance mechanism of the KIT receptor and could help to discover new therapeutics for KIT-based resistant tumor cells in GIST therapy.
The preclinical agent, KTN0182A, is an anti-KIT, pyrrolobenzodiazepine (PBD)-containing antibody-drug conjugate which shows anti-tumor activity in vitro and in vivo against a range of tumor types.
# Diagnostic relevance
Antibodies to CD117 are widely used in immunohistochemistry to help distinguish particular types of tumour in histological tissue sections. It is used primarily in the diagnosis of GISTs, which are positive for CD117, but negative for markers such as desmin and S-100, which are positive in smooth muscle and neural tumors, which have a similar appearance. In GISTs, CD117 staining is typically cytoplasmic, with stronger accentuation along the cell membranes. CD117 antibodies can also be used in the diagnosis of mast cell tumours and in distinguishing seminomas from embryonal carcinomas.
# Interactions
CD117 has been shown to interact with:
- APS,
- BCR,
- CD63,
- CD81,
- CD9,
- CRK,
- CRKL,
- DOK1,
- FES,
- GRB10,
- Grb2,
- KITLG,
- LNK,
- LYN,
- MATK,
- MPDZ,
- PIK3R1,
- PTPN11,
- PTPN6,
- STAT1,
- SOCS1,
- SOCS6,
- SRC, and
- TEC. | CD117
Mast/stem cell growth factor receptor (SCFR), also known as proto-oncogene c-Kit or tyrosine-protein kinase Kit or CD117, is a receptor tyrosine kinase protein that in humans is encoded by the KIT gene.[1] Multiple transcript variants encoding different isoforms have been found for this gene.[2][3]
KIT was first described by the German biochemist Axel Ullrich in 1987 as the cellular homolog of the feline sarcoma viral oncogene v-kit.[4]
# Cell surface marker
Cluster of differentiation (CD) molecules are markers on the cell surface, as recognized by specific sets of antibodies, used to identify the cell type, stage of differentiation and activity of a cell. CD117 is an important cell surface marker used to identify certain types of hematopoietic (blood) progenitors in the bone marrow. To be specific, hematopoietic stem cells (HSC), multipotent progenitors (MPP), and common myeloid progenitors (CMP) express high levels of CD117. Common lymphoid progenitors (CLP) express low surface levels of CD117.
CD117 also identifies the earliest thymocyte progenitors in the thymus. To be specific, early T lineage progenitors (ETP/DN1) and DN2 thymocytes express high levels of c-Kit. It is also a marker for mouse prostate stem cells.[5] In addition, mast cells, melanocytes in the skin, and interstitial cells of Cajal in the digestive tract express CD117. In humans, expression of c-kit in helper-like innate lymphoid cells (ILCs) which lack the expression of CRTH2 (CD294) is used to mark the ILC3 population.[6]
# Function
CD117 is a cytokine receptor expressed on the surface of hematopoietic stem cells as well as other cell types. Altered forms of this receptor may be associated with some types of cancer.[7] CD117 is a receptor tyrosine kinase type III, which binds to stem cell factor (a substance that causes certain types of cells to grow), also known as "steel factor" or "c-kit ligand". When this receptor binds to stem cell factor (SCF) it forms a dimer that activates its intrinsic tyrosine kinase activity, that in turn phosphorylates and activates signal transduction molecules that propagate the signal in the cell. Signaling through CD117 plays a role in cell survival, proliferation, and differentiation.
# Mobilization
Hematopoietic progenitor cells are normally present in the blood at low levels. Mobilization is the process by which progenitors are made to migrate from the bone marrow into the bloodstream, thus increasing their numbers in the blood. Mobilization is used clinically as a source of hematopoietic stem cells for hematopoietic stem cell transplantation (HSCT). Signaling through CD117 has been implicated in mobilization. At the current time, G-CSF is the main drug used for mobilization; it indirectly activates CD117. Plerixafor (an antagonist of CXCR4-SDF1) in combination with G-CSF, is also being used for mobilization of hematopoietic progenitor cells. Direct CD117 agonists are currently being developed as mobilization agents.
# Role in cancer
Activating mutations in this gene are associated with gastrointestinal stromal tumors, testicular seminoma, mast cell disease, melanoma, acute myeloid leukemia, while inactivating mutations are associated with the genetic defect piebaldism.[2]
## Anti-KIT therapies
CD117 is a proto-oncogene, meaning that overexpression or mutations of this protein can lead to cancer.[8] Seminomas, a subtype of testicular germ cell tumors, frequently have activating mutations in exon 17 of CD117. In addition, the gene encoding CD117 is frequently overexpressed and amplified in this tumor type, most commonly occurring as a single gene amplicon.[9] Mutations of CD117 have also been implicated in leukemia, a cancer of hematopoietic progenitors, melanoma, mast cell disease, and gastrointestinal stromal tumors (GISTs). The efficacy of imatinib (trade name Gleevec), a CD117 inhibitor, is determined by the mutation status of CD117:
When the mutation has occurred in exon 11 (as is the case many times in GISTs), the tumors are responsive to imatinib. However, if the mutation occurs in exon 17 (as is often the case in seminomas and leukemias), the receptor is not inhibited by imatinib. In those cases other inhibitors such as dasatinib and nilotinib can be used. Researchers investigated the dynamic behavior of wild type and mutant D816H KIT receptor, and emphasized the extended A-loop (EAL) region (805-850) by conducting computational analysis.[10] Their atomic investigation of mutant KIT receptor which emphasized on the EAL region provided a better insight into the understanding of the sunitinib resistance mechanism of the KIT receptor and could help to discover new therapeutics for KIT-based resistant tumor cells in GIST therapy.[10]
The preclinical agent, KTN0182A, is an anti-KIT, pyrrolobenzodiazepine (PBD)-containing antibody-drug conjugate which shows anti-tumor activity in vitro and in vivo against a range of tumor types.[11]
# Diagnostic relevance
Antibodies to CD117 are widely used in immunohistochemistry to help distinguish particular types of tumour in histological tissue sections. It is used primarily in the diagnosis of GISTs, which are positive for CD117, but negative for markers such as desmin and S-100, which are positive in smooth muscle and neural tumors, which have a similar appearance. In GISTs, CD117 staining is typically cytoplasmic, with stronger accentuation along the cell membranes. CD117 antibodies can also be used in the diagnosis of mast cell tumours and in distinguishing seminomas from embryonal carcinomas.[12]
# Interactions
CD117 has been shown to interact with:
- APS,[13]
- BCR,[14]
- CD63,[15]
- CD81,[15]
- CD9,[15]
- CRK,[16][16]
- CRKL,[17][18]
- DOK1,[19]
- FES,[20][20]
- GRB10,[21]
- Grb2,[22][23][24]
- KITLG,[25][26]
- LNK,[27]
- LYN,[19][28]
- MATK,[29][30]
- MPDZ,[31]
- PIK3R1,[17][22][32]
- PTPN11,[33][34]
- PTPN6,[34][35]
- STAT1,[36]
- SOCS1,[22]
- SOCS6,[37]
- SRC,[38] and
- TEC.[39] | https://www.wikidoc.org/index.php/C-KIT | |
7def0498a9ffe7e66872da66be572ae018f85144 | wikidoc | C-Met | C-Met
c-Met, also called tyrosine-protein kinase Met or hepatocyte growth factor receptor (HGFR), is a protein that in humans is encoded by the MET gene. The protein possesses tyrosine kinase activity. The primary single chain precursor protein is post-translationally cleaved to produce the alpha and beta subunits, which are disulfide linked to form the mature receptor.
MET is a single pass tyrosine kinase receptor essential for embryonic development, organogenesis and wound healing. Hepatocyte growth factor/Scatter Factor (HGF/SF) and its splicing isoform (NK1, NK2) are the only known ligands of the MET receptor. MET is normally expressed by cells of epithelial origin, while expression of HGF/SF is restricted to cells of mesenchymal origin. When HGF/SF binds its cognate receptor MET it induces its dimerization through a not yet completely understood mechanism leading to its activation.
Abnormal MET activation in cancer correlates with poor prognosis, where aberrantly active MET triggers tumor growth, formation of new blood vessels (angiogenesis) that supply the tumor with nutrients, and cancer spread to other organs (metastasis). MET is deregulated in many types of human malignancies, including cancers of kidney, liver, stomach, breast, and brain. Normally, only stem cells and progenitor cells express MET, which allows these cells to grow invasively in order to generate new tissues in an embryo or regenerate damaged tissues in an adult. However, cancer stem cells are thought to hijack the ability of normal stem cells to express MET, and thus become the cause of cancer persistence and spread to other sites in the body. Both the overexpression of Met/HGFR, as well as its autocrine activation by co-expression of its hepatocyte growth factor ligand, have been implicated in oncogenesis.
Various mutations in the MET gene are associated with papillary renal carcinoma.
# Gene
MET proto-oncogene (GeneID: 4233) has a total length of 125,982 bp, and it is located in the 7q31 locus of chromosome 7. MET is transcribed into a 6,641 bp mature mRNA, which is then translated into a 1,390 amino-acid MET protein.
# Protein
MET is a receptor tyrosine kinase (RTK) that is produced as a single-chain precursor. The precursor is proteolytically cleaved at a furin site to yield a highly glycosylated extracellular α-subunit and a transmembrane β-subunit, which are linked together by a disulfide bridge.
## Extracellular
- Region of homology to semaphorins (Sema domain), which includes the full α-chain and the N-terminal part of the β-chain
- Cysteine-rich MET-related sequence (MRS domain)
- Glycine-proline-rich repeats (G-P repeats)
- Four immunoglobulin-like structures (Ig domains), a typical protein-protein interaction region.
## Intracellular
A Juxtamembrane segment that contains:
- a serine residue (Ser 985), which inhibits the receptor kinase activity upon phosphorylation
- a tyrosine (Tyr 1003), which is responsible for MET polyubiquitination, endocytosis, and degradation upon interaction with the ubiquitin ligase CBL
- Tyrosine kinase domain, which mediates MET biological activity. Following MET activation, transphosphorylation occurs on Tyr 1234 and Tyr 1235
- C-terminal region contains two crucial tyrosines (Tyr 1349 and Tyr 1356), which are inserted into the multisubstrate docking site, capable of recruiting downstream adapter proteins with Src homology-2 (SH2) domains. The two tyrosines of the docking site have been reported to be necessary and sufficient for the signal transduction both in vitro.
# MET signaling pathway
MET activation by its ligand HGF induces MET kinase catalytic activity, which triggers transphosphorylation of the tyrosines Tyr 1234 and Tyr 1235. These two tyrosines engage various signal transducers, thus initiating a whole spectrum of biological activities driven by MET, collectively known as the invasive growth program. The transducers interact with the intracellular multisubstrate docking site of MET either directly, such as GRB2, SHC, SRC, and the p85 regulatory subunit of phosphatidylinositol-3 kinase (PI3K), or indirectly through the scaffolding protein Gab1
Tyr 1349 and Tyr 1356 of the multisubstrate docking site are both involved in the interaction with GAB1, SRC, and SHC, while only Tyr 1356 is involved in the recruitment of GRB2, phospholipase C γ (PLC-γ), p85, and SHP2.
GAB1 is a key coordinator of the cellular responses to MET and binds the MET intracellular region with high avidity, but low affinity. Upon interaction with MET, GAB1 becomes phosphorylated on several tyrosine residues which, in turn, recruit a number of signalling effectors, including PI3K, SHP2, and PLC-γ. GAB1 phosphorylation by MET results in a sustained signal that mediates most of the downstream signaling pathways.
## Activation of signal transduction
MET engagement activates multiple signal transduction pathways:
- The RAS pathway mediates HGF-induced scattering and proliferation signals, which lead to branching morphogenesis. Of note, HGF, differently from most mitogens, induces sustained RAS activation, and thus prolonged MAPK activity.
- The PI3K pathway is activated in two ways: PI3K can be either downstream of RAS, or it can be recruited directly through the multifunctional docking site. Activation of the PI3K pathway is currently associated with cell motility through remodeling of adhesion to the extracellular matrix as well as localized recruitment of transducers involved in cytoskeletal reorganization, such as RAC1 and PAK. PI3K activation also triggers a survival signal due to activation of the AKT pathway.
- The STAT pathway, together with the sustained MAPK activation, is necessary for the HGF-induced branching morphogenesis. MET activates the STAT3 transcription factor directly, through an SH2 domain.
- The beta-catenin pathway, a key component of the Wnt signaling pathway, translocates into the nucleus following MET activation and participates in transcriptional regulation of numerous genes.
- The Notch pathway, through transcriptional activation of Delta ligand (see DLL3).
# Role in development
MET mediates a complex program known as invasive growth. Activation of MET triggers mitogenesis, and morphogenesis.
During embryonic development, transformation of the flat, two-layer germinal disc into a three-dimensional body depends on transition of some cells from an epithelial phenotype to spindle-shaped cells with motile behaviour, a mesenchymal phenotype. This process is referred to as epithelial-mesenchymal transition (EMT). Later in embryonic development, MET is crucial for gastrulation, angiogenesis, myoblast migration, bone remodeling, and nerve sprouting among others. MET is essential for embryogenesis, because MET −/− mice die in utero due to severe defects in placental development. Along with Ectodysplasin A, it has been shown to be involved in the differentiation of anatomical placodes, precursors of scales, feathers and hair follicles in vertebrates. Furthermore, MET is required for such critical processes as liver regeneration and wound healing during adulthood.
HGF/MET axis is also involved in myocardial development. Both HGF and MET receptor mRNAs are co-expressed in cardiomyocytes from E7.5, soon after the heart has been determined, to E9.5. Transcripts for HGF ligand and receptor are first detected before the occurrence of cardiac beating and looping, and persist throughout the looping stage, when heart morphology begins to elaborate. In avian studies, HGF was found in the myocardial layer of the atrioventricular canal, in a developmental stage in which the epithelial to mesenchymal transformation (EMT) of the endocardial cushion occurs. However, MET is not essential for heart development, since α-MHCMet-KO mice show normal heart development.
# Expression
## Tissue distribution
MET is normally expressed by epithelial cells. However, MET is also found on endothelial cells, neurons, hepatocytes, hematopoietic cells, melanocytes and neonatal cardiomyocytes. HGF expression is restricted to cells of mesenchymal origin.
## Transcriptional control
MET transcription is activated by HGF and several growth factors. MET promoter has four putative binding sites for Ets, a family of transcription factors that control several invasive growth genes. ETS1 activates MET transcription in vitro. MET transcription is activated by hypoxia-inducible factor 1 (HIF1), which is activated by low concentration of intracellular oxygen. HIF1 can bind to one of the several hypoxia response elements (HREs) in the MET promoter. Hypoxia also activates transcription factor AP-1, which is involved in MET transcription.
# Clinical significance
## Role in cancer
MET pathway plays an important role in the development of cancer through:
- activation of key oncogenic pathways (RAS, PI3K, STAT3, beta-catenin);
- angiogenesis (sprouting of new blood vessels from pre-existing ones to supply a tumor with nutrients);
- scatter (cells dissociation due to metalloprotease production), which often leads to metastasis.
Coordinated down-regulation of both MET and its downstream effector extracellular signal-regulated kinase 2 (ERK2) by miR-199a- may be effective in inhibiting not only cell proliferation but also motility and invasive capabilities of tumor cells.
MET amplification has emerged as a potential biomarker of the clear cell tumor subtype.
The amplification of the cell surface receptor MET often drives resistance to anti-EGFR therapies in colorectal cancer.
## Role in autism
The SFARIgene database lists MET with an autism score of 2.0, which indicates that it is a strong candidate for playing a role in cases of autism. The database also identifies at least one study that found a role for MET in cases of schizophrenia. The gene was first implicated in autism in a study that identified a polymorphism in the promoter of the MET gene. The polymorphism reduces transcription by 50%. Further, the variant as an autism risk polymorphism has been replicated, and shown to be enriched in children with autism and gastrointestinal disturbances. A rare mutation that appears in two family members, one with autism and the other with a social and communication disorder. The role of the receptor in brain development is distinct from its role in other developmental processes. Activation of the MET receptor regulates synapse formation and can impact the development and function of circuits involved in social and emotional behavior.
## Role in heart function
In adult mice, MET is required to protect cardiomyocytes by preventing age-related oxidative stress, apoptosis, fibrosis and cardiac dysfunction. Moreover, MET inhibitors, such as Crizotinib or PF-04254644, have been tested by short-term treatments in cellular and preclinical models, and have been shown to induce cardiomyocytes death through ROS production, activation of caspases, metabolism alteration and blockage of ion channels.
In the injured heart, HGF/MET axis plays important roles in cardioprotection by promoting pro-survival (anti-apoptotic and anti-autophagic) effects in cardiomyocytes, angiogenesis, inhibition of fibrosis, anti-inflammatory and immunomodulatory signals, and regeneration through activation of cardiac stem cells.
# Interaction with tumour suppressor genes
## PTEN
PTEN (phosphatase and tensin homolog) is a tumor suppressor gene encoding a protein PTEN, which possesses lipid and protein phosphatase-dependent as well as phosphatase-independent activities. PTEN protein phosphatase is able to interfere with MET signaling by dephosphorylating either PIP3 generated by PI3K, or the p52 isoform of SHC. SHC dephosphorylation inhibits recruitment of the GRB2 adapter to activated MET.
## VHL
There is evidence of correlation between inactivation of VHL tumor suppressor gene and increased MET signaling in renal cell carcinoma (RCC) and also in malignant transformations of the heart.
# Cancer therapies targeting HGF/MET
Since tumor invasion and metastasis are the main cause of death in cancer patients, interfering with MET signaling appears to be a promising therapeutic approach. A comprehensive list of HGF and MET targeted experimental therapeutics for oncology now in human clinical trials can be found here.
## MET kinase inhibitors
Kinase inhibitors are low molecular weight molecules that prevent ATP binding to MET, thus inhibiting receptor transphosphorylation and recruitment of the downstream effectors. The limitations of kinase inhibitors include the facts that they only inhibit kinase-dependent MET activation, and that none of them is fully specific for MET.
- K252a (Fermentek Biotechnology) is a staurosporine analogue isolated from Nocardiopsis sp. soil fungi, and it is a potent inhibitor of all receptor tyrosine kinases (RTKs). At nanomolar concentrations, K252a inhibits both the wild type and the mutant (M1268T) MET function.
- SU11274 (SUGEN) specifically inhibits MET kinase activity and its subsequent signaling. SU11274 is also an effective inhibitor of the M1268T and H1112Y MET mutants, but not the L1213V and Y1248H mutants. SU11274 has been demonstrated to inhibit HGF-induced motility and invasion of epithelial and carcinoma cells.
- PHA-665752 (Pfizer) specifically inhibits MET kinase activity, and it has been demonstrated to represses both HGF-dependent and constitutive MET phosphorylation. Furthermore, some tumors harboring MET amplifications are highly sensitive to treatment with PHA-665752.
- ARQ197 (ArQule) is a promising selective inhibitor of MET, which entered a phase 2 clinical trial in 2008. (Failed a phase 3 in 2017)
- Foretinib (XL880, Exelixis) targets multiple receptor tyrosine kinases (RTKs) with growth-promoting and angiogenic properties. The primary targets of foretinib are MET, VEGFR2, and KDR. Foretinib has completed a phase 2 clinical trials with indications for papillary renal cell carcinoma, gastric cancer, and head and neck cancer.
- SGX523 (SGX Pharmaceuticals) specifically inhibits MET at low nanomolar concentrations.
- MP470 (SuperGen) is a novel inhibitor of c-KIT, MET, PDGFR, Flt3, and AXL. Phase I clinical trial of MP470 had been announced in 2007.
## HGF inhibitors
Since HGF is the only known ligand of MET, formation of a HGF:MET complex blocks MET biological activity. For this purpose, truncated HGF, anti-HGF neutralizing antibodies, and an uncleavable form of HGF have been utilized so far. The major limitation of HGF inhibitors is that they block only HGF-dependent MET activation.
- NK4 competes with HGF as it binds MET without inducing receptor activation, thus behaving as a full antagonist. NK4 is a molecule bearing the N-terminal hairpin and the four kringle domains of HGF. Moreover, NK4 is structurally similar to angiostatins, which is why it possesses anti-angiogenic activity.
- Neutralizing anti-HGF antibodies were initially tested in combination, and it was shown that at least three antibodies, acting on different HGF epitopes, are necessary to prevent MET tyrosine kinase activation. More recently, it has been demonstrated that fully human monoclonal antibodies can individually bind and neutralize human HGF, leading to regression of tumors in mouse models. Two anti-HGF antibodies are currently available: the humanized AV299 (AVEO), and the fully human AMG102 (Amgen).
- Uncleavable HGF is an engineered form of pro-HGF carrying a single amino-acid substitution, which prevents the maturation of the molecule. Uncleavable HGF is capable of blocking MET-induced biological responses by binding MET with high affinity and displacing mature HGF. Moreover, uncleavable HGF competes with the wild-type endogenous pro-HGF for the catalytic domain of proteases that cleave HGF precursors. Local and systemic expression of uncleavable HGF inhibits tumor growth and, more importantly, prevents metastasis.
## Decoy MET
Decoy MET refers to a soluble truncated MET receptor. Decoys are able to inhibit MET activation mediated by both HGF-dependent and independent mechanisms, as decoys prevent both the ligand binding and the MET receptor homodimerization. CGEN241 (Compugen) is a decoy MET that is highly efficient in inhibiting tumor growth and preventing metastasis in animal models.
## Immunotherapy targeting MET
Drugs used for immunotherapy can act either passively by enhancing the immunologic response to MET-expressing tumor cells, or actively by stimulating immune cells and altering differentiation/growth of tumor cells.
### Passive immunotherapy
Administering monoclonal antibodies (mAbs) is a form of passive immunotherapy. MAbs facilitate destruction of tumor cells by complement-dependent cytotoxicity (CDC) and cell-mediated cytotoxicity (ADCC). In CDC, mAbs bind to specific antigen, leading to activation of the complement cascade, which in turn leads to formation of pores in tumor cells. In ADCC, the Fab domain of a mAb binds to a tumor antigen, and Fc domain binds to Fc receptors present on effector cells (phagocytes and NK cells), thus forming a bridge between an effector and a target cells. This induces the effector cell activation, leading to phagocytosis of the tumor cell by neutrophils and macrophages. Furthermore, NK cells release cytotoxic molecules, which lyse tumor cells.
- DN30 is monoclonal anti-MET antibody that recognizes the extracellular portion of MET. DN30 induces both shedding of the MET ectodomain as well as cleavage of the intracellular domain, which is successively degraded by proteasome machinery. As a consequence, on one side MET is inactivated, and on the other side the shed portion of extracellular MET hampers activation of other MET receptors, acting as a decoy. DN30 inhibits tumour growth and prevents metastasis in animal models.
- OA-5D5 is one-armed monoclonal anti-MET antibody that was demonstrated to inhibit orthotopic pancreatic and glioblastoma tumor growth and to improve survival in tumor xenograft models. OA-5D5 is produced as a recombinant protein in Escherichia coli. It is composed of murine variable domains for the heavy and light chains with human IgG1 constant domains. The antibody blocks HGF binding to MET in a competitive fashion.
### Active immunotherapy
Active immunotherapy to MET-expressing tumors can be achieved by administering cytokines, such as interferons (IFNs) and interleukins (IL-2), which triggers non-specific stimulation of numerous immune cells. IFNs have been tested as therapies for many types of cancers and have demonstrated therapeutic benefits. IL-2 has been approved by the U.S. Food and Drug Administration (FDA) for the treatment of renal cell carcinoma and metastatic melanoma, which often have deregulated MET activity.
# Interactions
Met has been shown to interact with:
- CDH1,
- Cbl gene,
- GLMN,
- Grb2,
- Hepatocyte growth factor,
- PTPmu, and
- RANBP9 | C-Met
c-Met, also called tyrosine-protein kinase Met or hepatocyte growth factor receptor (HGFR),[1][2] is a protein that in humans is encoded by the MET gene. The protein possesses tyrosine kinase activity.[3] The primary single chain precursor protein is post-translationally cleaved to produce the alpha and beta subunits, which are disulfide linked to form the mature receptor.
MET is a single pass tyrosine kinase receptor essential for embryonic development, organogenesis and wound healing. Hepatocyte growth factor/Scatter Factor (HGF/SF) and its splicing isoform (NK1, NK2) are the only known ligands of the MET receptor. MET is normally expressed by cells of epithelial origin, while expression of HGF/SF is restricted to cells of mesenchymal origin. When HGF/SF binds its cognate receptor MET it induces its dimerization through a not yet completely understood mechanism leading to its activation.
Abnormal MET activation in cancer correlates with poor prognosis, where aberrantly active MET triggers tumor growth, formation of new blood vessels (angiogenesis) that supply the tumor with nutrients, and cancer spread to other organs (metastasis). MET is deregulated in many types of human malignancies, including cancers of kidney, liver, stomach, breast, and brain. Normally, only stem cells and progenitor cells express MET, which allows these cells to grow invasively in order to generate new tissues in an embryo or regenerate damaged tissues in an adult. However, cancer stem cells are thought to hijack the ability of normal stem cells to express MET, and thus become the cause of cancer persistence and spread to other sites in the body. Both the overexpression of Met/HGFR, as well as its autocrine activation by co-expression of its hepatocyte growth factor ligand, have been implicated in oncogenesis.[4][5]
Various mutations in the MET gene are associated with papillary renal carcinoma.[6]
# Gene
MET proto-oncogene (GeneID: 4233) has a total length of 125,982 bp, and it is located in the 7q31 locus of chromosome 7.[7] MET is transcribed into a 6,641 bp mature mRNA, which is then translated into a 1,390 amino-acid MET protein.
# Protein
MET is a receptor tyrosine kinase (RTK) that is produced as a single-chain precursor. The precursor is proteolytically cleaved at a furin site to yield a highly glycosylated extracellular α-subunit and a transmembrane β-subunit, which are linked together by a disulfide bridge.[9]
## Extracellular
- Region of homology to semaphorins (Sema domain), which includes the full α-chain and the N-terminal part of the β-chain
- Cysteine-rich MET-related sequence (MRS domain)
- Glycine-proline-rich repeats (G-P repeats)
- Four immunoglobulin-like structures (Ig domains), a typical protein-protein interaction region.[9]
## Intracellular
A Juxtamembrane segment that contains:
- a serine residue (Ser 985), which inhibits the receptor kinase activity upon phosphorylation[10]
- a tyrosine (Tyr 1003), which is responsible for MET polyubiquitination, endocytosis, and degradation upon interaction with the ubiquitin ligase CBL[11]
- Tyrosine kinase domain, which mediates MET biological activity. Following MET activation, transphosphorylation occurs on Tyr 1234 and Tyr 1235
- C-terminal region contains two crucial tyrosines (Tyr 1349 and Tyr 1356), which are inserted into the multisubstrate docking site, capable of recruiting downstream adapter proteins with Src homology-2 (SH2) domains.[12] The two tyrosines of the docking site have been reported to be necessary and sufficient for the signal transduction both in vitro.[12][13]
# MET signaling pathway
MET activation by its ligand HGF induces MET kinase catalytic activity, which triggers transphosphorylation of the tyrosines Tyr 1234 and Tyr 1235. These two tyrosines engage various signal transducers,[15] thus initiating a whole spectrum of biological activities driven by MET, collectively known as the invasive growth program. The transducers interact with the intracellular multisubstrate docking site of MET either directly, such as GRB2, SHC,[16] SRC, and the p85 regulatory subunit of phosphatidylinositol-3 kinase (PI3K),[16] or indirectly through the scaffolding protein Gab1[17]
Tyr 1349 and Tyr 1356 of the multisubstrate docking site are both involved in the interaction with GAB1, SRC, and SHC, while only Tyr 1356 is involved in the recruitment of GRB2, phospholipase C γ (PLC-γ), p85, and SHP2.[18]
GAB1 is a key coordinator of the cellular responses to MET and binds the MET intracellular region with high avidity, but low affinity.[19] Upon interaction with MET, GAB1 becomes phosphorylated on several tyrosine residues which, in turn, recruit a number of signalling effectors, including PI3K, SHP2, and PLC-γ. GAB1 phosphorylation by MET results in a sustained signal that mediates most of the downstream signaling pathways.[20]
## Activation of signal transduction
MET engagement activates multiple signal transduction pathways:
- The RAS pathway mediates HGF-induced scattering and proliferation signals, which lead to branching morphogenesis.[21] Of note, HGF, differently from most mitogens, induces sustained RAS activation, and thus prolonged MAPK activity.[22]
- The PI3K pathway is activated in two ways: PI3K can be either downstream of RAS, or it can be recruited directly through the multifunctional docking site.[23] Activation of the PI3K pathway is currently associated with cell motility through remodeling of adhesion to the extracellular matrix as well as localized recruitment of transducers involved in cytoskeletal reorganization, such as RAC1 and PAK. PI3K activation also triggers a survival signal due to activation of the AKT pathway.[8]
- The STAT pathway, together with the sustained MAPK activation, is necessary for the HGF-induced branching morphogenesis. MET activates the STAT3 transcription factor directly, through an SH2 domain.[24]
- The beta-catenin pathway, a key component of the Wnt signaling pathway, translocates into the nucleus following MET activation and participates in transcriptional regulation of numerous genes.[25]
- The Notch pathway, through transcriptional activation of Delta ligand (see DLL3).[14][26]
# Role in development
MET mediates a complex program known as invasive growth.[8] Activation of MET triggers mitogenesis, and morphogenesis.[27][28]
During embryonic development, transformation of the flat, two-layer germinal disc into a three-dimensional body depends on transition of some cells from an epithelial phenotype to spindle-shaped cells with motile behaviour, a mesenchymal phenotype. This process is referred to as epithelial-mesenchymal transition (EMT).[29] Later in embryonic development, MET is crucial for gastrulation, angiogenesis, myoblast migration, bone remodeling, and nerve sprouting among others.[30] MET is essential for embryogenesis, because MET −/− mice die in utero due to severe defects in placental development.[31] Along with Ectodysplasin A, it has been shown to be involved in the differentiation of anatomical placodes, precursors of scales, feathers and hair follicles in vertebrates.[32] Furthermore, MET is required for such critical processes as liver regeneration and wound healing during adulthood.[8]
HGF/MET axis is also involved in myocardial development. Both HGF and MET receptor mRNAs are co-expressed in cardiomyocytes from E7.5, soon after the heart has been determined, to E9.5. Transcripts for HGF ligand and receptor are first detected before the occurrence of cardiac beating and looping, and persist throughout the looping stage, when heart morphology begins to elaborate.[33] In avian studies, HGF was found in the myocardial layer of the atrioventricular canal, in a developmental stage in which the epithelial to mesenchymal transformation (EMT) of the endocardial cushion occurs.[34] However, MET is not essential for heart development, since α-MHCMet-KO mice show normal heart development.[35]
# Expression
## Tissue distribution
MET is normally expressed by epithelial cells.[8] However, MET is also found on endothelial cells, neurons, hepatocytes, hematopoietic cells, melanocytes and neonatal cardiomyocytes.[28][36] HGF expression is restricted to cells of mesenchymal origin.[29]
## Transcriptional control
MET transcription is activated by HGF and several growth factors.[37] MET promoter has four putative binding sites for Ets, a family of transcription factors that control several invasive growth genes.[37] ETS1 activates MET transcription in vitro.[38] MET transcription is activated by hypoxia-inducible factor 1 (HIF1), which is activated by low concentration of intracellular oxygen.[39] HIF1 can bind to one of the several hypoxia response elements (HREs) in the MET promoter.[29] Hypoxia also activates transcription factor AP-1, which is involved in MET transcription.[29]
# Clinical significance
## Role in cancer
MET pathway plays an important role in the development of cancer through:
- activation of key oncogenic pathways (RAS, PI3K, STAT3, beta-catenin);
- angiogenesis (sprouting of new blood vessels from pre-existing ones to supply a tumor with nutrients);
- scatter (cells dissociation due to metalloprotease production), which often leads to metastasis.[40]
Coordinated down-regulation of both MET and its downstream effector extracellular signal-regulated kinase 2 (ERK2) by miR-199a* may be effective in inhibiting not only cell proliferation but also motility and invasive capabilities of tumor cells.[41]
MET amplification has emerged as a potential biomarker of the clear cell tumor subtype.[42]
The amplification of the cell surface receptor MET often drives resistance to anti-EGFR therapies in colorectal cancer.[43]
## Role in autism
The SFARIgene database lists MET with an autism score of 2.0, which indicates that it is a strong candidate for playing a role in cases of autism. The database also identifies at least one study that found a role for MET in cases of schizophrenia. The gene was first implicated in autism in a study that identified a polymorphism in the promoter of the MET gene.[44] The polymorphism reduces transcription by 50%. Further, the variant as an autism risk polymorphism has been replicated, and shown to be enriched in children with autism and gastrointestinal disturbances.[45] A rare mutation that appears in two family members, one with autism and the other with a social and communication disorder.[46] The role of the receptor in brain development is distinct from its role in other developmental processes. Activation of the MET receptor regulates synapse formation[47][48][49][50][51] and can impact the development and function of circuits involved in social and emotional behavior.[52]
## Role in heart function
In adult mice, MET is required to protect cardiomyocytes by preventing age-related oxidative stress, apoptosis, fibrosis and cardiac dysfunction.[35] Moreover, MET inhibitors, such as Crizotinib or PF-04254644, have been tested by short-term treatments in cellular and preclinical models, and have been shown to induce cardiomyocytes death through ROS production, activation of caspases, metabolism alteration and blockage of ion channels.[53][54]
In the injured heart, HGF/MET axis plays important roles in cardioprotection by promoting pro-survival (anti-apoptotic and anti-autophagic) effects in cardiomyocytes, angiogenesis, inhibition of fibrosis, anti-inflammatory and immunomodulatory signals, and regeneration through activation of cardiac stem cells.[55][56]
# Interaction with tumour suppressor genes
## PTEN
PTEN (phosphatase and tensin homolog) is a tumor suppressor gene encoding a protein PTEN, which possesses lipid and protein phosphatase-dependent as well as phosphatase-independent activities.[57] PTEN protein phosphatase is able to interfere with MET signaling by dephosphorylating either PIP3 generated by PI3K, or the p52 isoform of SHC. SHC dephosphorylation inhibits recruitment of the GRB2 adapter to activated MET.[14]
## VHL
There is evidence of correlation between inactivation of VHL tumor suppressor gene and increased MET signaling in renal cell carcinoma (RCC) and also in malignant transformations of the heart.[58][59]
# Cancer therapies targeting HGF/MET
Since tumor invasion and metastasis are the main cause of death in cancer patients, interfering with MET signaling appears to be a promising therapeutic approach. A comprehensive list of HGF and MET targeted experimental therapeutics for oncology now in human clinical trials can be found here.
## MET kinase inhibitors
Kinase inhibitors are low molecular weight molecules that prevent ATP binding to MET, thus inhibiting receptor transphosphorylation and recruitment of the downstream effectors. The limitations of kinase inhibitors include the facts that they only inhibit kinase-dependent MET activation, and that none of them is fully specific for MET.
- K252a (Fermentek Biotechnology) is a staurosporine analogue isolated from Nocardiopsis sp. soil fungi, and it is a potent inhibitor of all receptor tyrosine kinases (RTKs). At nanomolar concentrations, K252a inhibits both the wild type and the mutant (M1268T) MET function.[60]
- SU11274 (SUGEN) specifically inhibits MET kinase activity and its subsequent signaling. SU11274 is also an effective inhibitor of the M1268T and H1112Y MET mutants, but not the L1213V and Y1248H mutants.[61] SU11274 has been demonstrated to inhibit HGF-induced motility and invasion of epithelial and carcinoma cells.[62]
- PHA-665752 (Pfizer) specifically inhibits MET kinase activity, and it has been demonstrated to represses both HGF-dependent and constitutive MET phosphorylation.[63] Furthermore, some tumors harboring MET amplifications are highly sensitive to treatment with PHA-665752.[64]
- ARQ197 (ArQule) is a promising selective inhibitor of MET, which entered a phase 2 clinical trial in 2008. (Failed a phase 3 in 2017)
- Foretinib (XL880, Exelixis) targets multiple receptor tyrosine kinases (RTKs) with growth-promoting and angiogenic properties. The primary targets of foretinib are MET, VEGFR2, and KDR. Foretinib has completed a phase 2 clinical trials with indications for papillary renal cell carcinoma, gastric cancer, and head and neck cancer.[65]
- SGX523 (SGX Pharmaceuticals) specifically inhibits MET at low nanomolar concentrations.
- MP470 (SuperGen) is a novel inhibitor of c-KIT, MET, PDGFR, Flt3, and AXL. Phase I clinical trial of MP470 had been announced in 2007.
## HGF inhibitors
Since HGF is the only known ligand of MET, formation of a HGF:MET complex blocks MET biological activity. For this purpose, truncated HGF, anti-HGF neutralizing antibodies, and an uncleavable form of HGF have been utilized so far. The major limitation of HGF inhibitors is that they block only HGF-dependent MET activation.
- NK4 competes with HGF as it binds MET without inducing receptor activation, thus behaving as a full antagonist. NK4 is a molecule bearing the N-terminal hairpin and the four kringle domains of HGF. Moreover, NK4 is structurally similar to angiostatins, which is why it possesses anti-angiogenic activity.[66]
- Neutralizing anti-HGF antibodies were initially tested in combination, and it was shown that at least three antibodies, acting on different HGF epitopes, are necessary to prevent MET tyrosine kinase activation.[67] More recently, it has been demonstrated that fully human monoclonal antibodies can individually bind and neutralize human HGF, leading to regression of tumors in mouse models.[68] Two anti-HGF antibodies are currently available: the humanized AV299 (AVEO), and the fully human AMG102 (Amgen).
- Uncleavable HGF is an engineered form of pro-HGF carrying a single amino-acid substitution, which prevents the maturation of the molecule. Uncleavable HGF is capable of blocking MET-induced biological responses by binding MET with high affinity and displacing mature HGF. Moreover, uncleavable HGF competes with the wild-type endogenous pro-HGF for the catalytic domain of proteases that cleave HGF precursors. Local and systemic expression of uncleavable HGF inhibits tumor growth and, more importantly, prevents metastasis.[69]
## Decoy MET
Decoy MET refers to a soluble truncated MET receptor. Decoys are able to inhibit MET activation mediated by both HGF-dependent and independent mechanisms, as decoys prevent both the ligand binding and the MET receptor homodimerization. CGEN241 (Compugen) is a decoy MET that is highly efficient in inhibiting tumor growth and preventing metastasis in animal models.[70]
## Immunotherapy targeting MET
Drugs used for immunotherapy can act either passively by enhancing the immunologic response to MET-expressing tumor cells, or actively by stimulating immune cells and altering differentiation/growth of tumor cells.[71]
### Passive immunotherapy
Administering monoclonal antibodies (mAbs) is a form of passive immunotherapy. MAbs facilitate destruction of tumor cells by complement-dependent cytotoxicity (CDC) and cell-mediated cytotoxicity (ADCC). In CDC, mAbs bind to specific antigen, leading to activation of the complement cascade, which in turn leads to formation of pores in tumor cells. In ADCC, the Fab domain of a mAb binds to a tumor antigen, and Fc domain binds to Fc receptors present on effector cells (phagocytes and NK cells), thus forming a bridge between an effector and a target cells. This induces the effector cell activation, leading to phagocytosis of the tumor cell by neutrophils and macrophages. Furthermore, NK cells release cytotoxic molecules, which lyse tumor cells.[71]
- DN30 is monoclonal anti-MET antibody that recognizes the extracellular portion of MET. DN30 induces both shedding of the MET ectodomain as well as cleavage of the intracellular domain, which is successively degraded by proteasome machinery. As a consequence, on one side MET is inactivated, and on the other side the shed portion of extracellular MET hampers activation of other MET receptors, acting as a decoy. DN30 inhibits tumour growth and prevents metastasis in animal models.[72]
- OA-5D5 is one-armed monoclonal anti-MET antibody that was demonstrated to inhibit orthotopic pancreatic[73] and glioblastoma[74] tumor growth and to improve survival in tumor xenograft models. OA-5D5 is produced as a recombinant protein in Escherichia coli. It is composed of murine variable domains for the heavy and light chains with human IgG1 constant domains. The antibody blocks HGF binding to MET in a competitive fashion.
### Active immunotherapy
Active immunotherapy to MET-expressing tumors can be achieved by administering cytokines, such as interferons (IFNs) and interleukins (IL-2), which triggers non-specific stimulation of numerous immune cells. IFNs have been tested as therapies for many types of cancers and have demonstrated therapeutic benefits. IL-2 has been approved by the U.S. Food and Drug Administration (FDA) for the treatment of renal cell carcinoma and metastatic melanoma, which often have deregulated MET activity.[71]
# Interactions
Met has been shown to interact with:
- CDH1,[75]
- Cbl gene,[76][77]
- GLMN,[78]
- Grb2,[79][80]
- Hepatocyte growth factor,[81][82]
- PTPmu,[83] and
- RANBP9[84] | https://www.wikidoc.org/index.php/C-MET | |
ce47d62402ff7a369aced046f45b0482a1f641e1 | wikidoc | c-Raf | c-Raf
# Overview
c-raf is gene that codes for a protein kinase. That protein is sometimes called c-Raf and will be called "Raf-1" here. The Raf-1 protein functions in the MAPK/ERK signal transduction pathway as part of a protein kinase cascade. Raf-1 is a serine/threonine-specific kinase (EC 2.7.11.1).
Raf-1 is a MAP kinase kinase kinase (MAP3K) which functions downstream of the Ras family of membrane associated GTPases to which it binds directly. Once activated Raf-1 can phosphorylate to activate the dual specificity protein kinases MEK1 and MEK2 which in turn phosphorylate to activate the serine/threonine specific protein kinases ERK1 and ERK2. Activated ERKs are pleiotropic effectors of cell physiology and play an important role in the control of gene expression involved in the cell division cycle, apoptosis, cell differentiation and cell migration.
# Discovery and role in cancer
The first raf gene that was found was the oncogene v-raf. Normal (non-oncogenic) cellular homologs of v-raf were soon found to be conserved components of eukaryotic genomes and it was shown that they could mutate and become oncogenes. A-Raf (Online Mendelian Inheritance in Man (OMIM) 311010) and B-Raf (Online Mendelian Inheritance in Man (OMIM) 164757) are two protein kinases with similar sequences to Raf-1. Mutations in B-Raf genes are found in several types of cancer. The Raf kinases are targets for anticancer drug development.
# Regulation of Raf kinase activity
Raf-1 was shown to bind efficiently to Ras only when Ras is bound to GTP, not GDP.
In the MAPK/ERK pathway Raf-1 becomes activated when it binds to Ras. It is thought that phosphorylation of Raf-1 (at sites such as serine-338) upon binding of Raf-1 to Ras locks Raf-1 into an activated conformation that is then independent of binding to Ras for the continued activity of Raf-1. Several MAPK kinase kinase kinases have been suggested to be important for phosphorylation of Raf-1 as well as positive feedback phosphorylation by MAPK (ERK).
Binding of 14-3-3ζ to phosphorylated serine-259 of Raf-1 is associated with inhibition of Raf-1 kinase activity. As shown in the figure (to the right), it is thought that a 14-3-3 dimer can bind to two phosphoserines of Raf-1 when it is inactive. Dephosphorylation of serine-259 has been associated with activation of Raf-1. In the model shown, the binding of GTP to Ras and the dephosphorylation of serine-259 of Raf-1 allows Raf-1 to take on a conformation that allows binding of Raf-1 to Ras-GTP. This represents a conformation in which Raf-1 can phosphorylate the downstream target MEK.
# Targets of Raf-1
In the MAPK/ERK pathway Raf-1 phosphorylates and activates MEK, a MAPK kinase. This allows Raf-1 to function as part of a kinase cascade: Raf-1 phosphorylates MEK which phosphorylates MAPK (see MAPK/ERK pathway). | c-Raf
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
# Overview
c-raf is gene that codes for a protein kinase. That protein is sometimes called c-Raf and will be called "Raf-1" here. The Raf-1 protein functions in the MAPK/ERK signal transduction pathway as part of a protein kinase cascade. Raf-1 is a serine/threonine-specific kinase (EC 2.7.11.1).
Raf-1 is a MAP kinase kinase kinase (MAP3K) which functions downstream of the Ras family of membrane associated GTPases to which it binds directly. Once activated Raf-1 can phosphorylate to activate the dual specificity protein kinases MEK1 and MEK2 which in turn phosphorylate to activate the serine/threonine specific protein kinases ERK1 and ERK2. Activated ERKs are pleiotropic effectors of cell physiology and play an important role in the control of gene expression involved in the cell division cycle, apoptosis, cell differentiation and cell migration. [Contributed text][1]
# Discovery and role in cancer
The first raf gene that was found was the oncogene v-raf.[2] Normal (non-oncogenic) cellular homologs of v-raf were soon found to be conserved components of eukaryotic genomes and it was shown that they could mutate and become oncogenes.[3] A-Raf (Online Mendelian Inheritance in Man (OMIM) 311010) and B-Raf (Online Mendelian Inheritance in Man (OMIM) 164757) are two protein kinases with similar sequences to Raf-1. Mutations in B-Raf genes are found in several types of cancer. The Raf kinases are targets for anticancer drug development.[4]
# Regulation of Raf kinase activity
Raf-1 was shown to bind efficiently to Ras only when Ras is bound to GTP, not GDP.[5]
In the MAPK/ERK pathway Raf-1 becomes activated when it binds to Ras.[6] It is thought that phosphorylation of Raf-1 (at sites such as serine-338) upon binding of Raf-1 to Ras locks Raf-1 into an activated conformation that is then independent of binding to Ras for the continued activity of Raf-1.[7] Several MAPK kinase kinase kinases have been suggested to be important for phosphorylation of Raf-1 as well as positive feedback phosphorylation by MAPK (ERK).[8]
Binding of 14-3-3ζ to phosphorylated serine-259 of Raf-1 is associated with inhibition of Raf-1 kinase activity. As shown in the figure (to the right), it is thought that a 14-3-3 dimer can bind to two phosphoserines of Raf-1 when it is inactive. Dephosphorylation of serine-259 has been associated with activation of Raf-1.[9] In the model shown, the binding of GTP to Ras and the dephosphorylation of serine-259 of Raf-1 allows Raf-1 to take on a conformation that allows binding of Raf-1 to Ras-GTP. This represents a conformation in which Raf-1 can phosphorylate the downstream target MEK.
# Targets of Raf-1
In the MAPK/ERK pathway Raf-1 phosphorylates and activates MEK, a MAPK kinase.[10] This allows Raf-1 to function as part of a kinase cascade: Raf-1 phosphorylates MEK which phosphorylates MAPK (see MAPK/ERK pathway). | https://www.wikidoc.org/index.php/C-Raf | |
3853c43643959730339e66a6442d19d9eb09ac07 | wikidoc | C1QBP | C1QBP
Complement component 1 Q subcomponent-binding protein, mitochondrial is a protein that in humans is encoded by the C1QBP gene.
The human complement subcomponent C1q associates with C1r and C1s in order to yield the first component of the serum complement system. The protein encoded by this gene is known to bind to the globular heads of C1q molecules and inhibit C1 activation. This protein has also been identified as the p32 subunit of pre-mRNA splicing factor SF2, as well as a hyaluronic acid-binding protein.
# Interactions
C1QBP has been shown to interact with Protein kinase D1, BAT2, PRKCD, PKC alpha and Protein kinase Mζ. | C1QBP
Complement component 1 Q subcomponent-binding protein, mitochondrial is a protein that in humans is encoded by the C1QBP gene.[1][2][3]
The human complement subcomponent C1q associates with C1r and C1s in order to yield the first component of the serum complement system. The protein encoded by this gene is known to bind to the globular heads of C1q molecules and inhibit C1 activation. This protein has also been identified as the p32 subunit of pre-mRNA splicing factor SF2, as well as a hyaluronic acid-binding protein.[3]
# Interactions
C1QBP has been shown to interact with Protein kinase D1,[4] BAT2,[5] PRKCD,[4] PKC alpha[4] and Protein kinase Mζ.[4] | https://www.wikidoc.org/index.php/C1QBP | |
63994e7b5bc4fc3025334ff234a13864907409e2 | wikidoc | C1QL1 | C1QL1
The complement component 1, q subcomponent-like 1 (or C1QL1) is encoded by a gene located at chromosome 17q21.31. It is a secreted protein and is 258 amino acids in length.
The protein is widely expressed but its expression is highest in the brain and may also be involved in regulation of motor control.
The pre-mRNA of this protein is subject to RNA editing.
# Protein function
Its physiological function is unknown. It is a member of the C1Q domain proteins which have important signalling roles in inflammation and in adaptive immunity.
# RNA editing
## Editing type
The pre-mRNA of this protein is subject to A to I RNA editing, which is catalyzed by a family of adenosine deaminases acting on RNA (ADARs) that specifically recognize adenosines within double-stranded regions of pre-mRNAs and deaminate them to inosine. Inosines are recognised as guanosine by the cell's translational machinery. There are three members of the ADAR family: ADARs 1-3, with ADAR 1 and ADAR 2 being the only enzymatically active members. ADAR 3 is thought to have a regulatory role in the brain. ADAR 1 and ADAR 2 are widely expressed in tissues while ADAR 3 is restricted to the brain. The double-stranded regions of RNA are formed by base-pairing between residues in a region complementary to the region of the editing site. This complementary region is usually found in a neighbouring intron but can also be located in an exonic sequence. The region that pairs with the editing region is known as an Editing Complementary Sequence (ECS).
## Editing sites
The candidate editing sites were determined experimentally by comparison of cDNA sequences and genomically encoded DNA from the same individual to avoid single nucleotide polymorphisms (SNPs). Two of the three editing sites found in mouse gene were found in the human transcript.
However, only the Q/R site was detected in all RNA, with the T/A site detected just once. Both sites are found within exon 1.
Q/R site
This site is found in exon 1 at position 66. Editing results in a codon change from a Glutamine codon to an Arginine codon.
T/A site
This site is also found in exon 1, at position 63. It was only detected in one genomic sample indicating that the edited residue may be an SNP. However, the secondary structure of the RNA is predicted, around the editing site, to be highly conserved in mice and humans. This indicates that the T/A site may still be shown to be a site of A to I RNA editing. Editing at this site would result in an amino acid change from a Threonine to an Alanine.
The ECS is also predicted to be found within exon 1 at a location 5' to the editing region.
## Editing regulation
Editing is differentially expressed in the cerebellum and cortex. This regulation is also present in mice suggesting conservation of editing regulation. No editing has been detected in human lung, heart, kidney or spleen tissue.
## Evolutionary conservation
The sequence of exon 1 is highly conserved in mammalian species and editing of the pre-mRNA of this protein is likely to occur in mice, rat, dog and cow as well as humans. Even though the ECS is not conserved in non-mammals, an alternative ECS has been predicted in Zebrafish with a similar structure but in a different location. The Ecs is found downstram of the editing sites.
## Effects on Protein structure
These predicted editing sites result in the translation of an Arginine instead of a Glutamine at the Q/R site and an Alanine instead of a Threonine at the T/A site. These codon changes are nonsynomonous. Since the editing sites are located just before a collagen like trimerization domain, editing may effect protein oligomerization. This region is also likely to be a protease domain. It is not known if the amino acid changes caused by editing could have an effect on these domains. | C1QL1
The complement component 1, q subcomponent-like 1 (or C1QL1) is encoded by a gene located at chromosome 17q21.31. It is a secreted protein and is 258 amino acids in length.[1]
The protein is widely expressed but its expression is highest in the brain and may also be involved in regulation of motor control.[2]
The pre-mRNA of this protein is subject to RNA editing.[3]
# Protein function
Its physiological function is unknown. It is a member of the C1Q domain proteins which have important signalling roles in inflammation and in adaptive immunity.[4]
# RNA editing
## Editing type
The pre-mRNA of this protein is subject to A to I RNA editing, which is catalyzed by a family of adenosine deaminases acting on RNA (ADARs) that specifically recognize adenosines within double-stranded regions of pre-mRNAs and deaminate them to inosine. Inosines are recognised as guanosine by the cell's translational machinery. There are three members of the ADAR family: ADARs 1-3, with ADAR 1 and ADAR 2 being the only enzymatically active members. ADAR 3 is thought to have a regulatory role in the brain. ADAR 1 and ADAR 2 are widely expressed in tissues while ADAR 3 is restricted to the brain. The double-stranded regions of RNA are formed by base-pairing between residues in a region complementary to the region of the editing site. This complementary region is usually found in a neighbouring intron but can also be located in an exonic sequence. The region that pairs with the editing region is known as an Editing Complementary Sequence (ECS).
## Editing sites
The candidate editing sites were determined experimentally by comparison of cDNA sequences and genomically encoded DNA from the same individual to avoid single nucleotide polymorphisms (SNPs). Two of the three editing sites found in mouse gene were found in the human transcript.[3]
However, only the Q/R site was detected in all RNA, with the T/A site detected just once. Both sites are found within exon 1.[3]
Q/R site
This site is found in exon 1 at position 66. Editing results in a codon change from a Glutamine codon to an Arginine codon.
T/A site
This site is also found in exon 1, at position 63. It was only detected in one genomic sample indicating that the edited residue may be an SNP. However, the secondary structure of the RNA is predicted, around the editing site, to be highly conserved in mice and humans. This indicates that the T/A site may still be shown to be a site of A to I RNA editing. Editing at this site would result in an amino acid change from a Threonine to an Alanine.
The ECS is also predicted to be found within exon 1 at a location 5' to the editing region.[3]
## Editing regulation
Editing is differentially expressed in the cerebellum and cortex. This regulation is also present in mice suggesting conservation of editing regulation. No editing has been detected in human lung, heart, kidney or spleen tissue.[3]
## Evolutionary conservation
The sequence of exon 1 is highly conserved in mammalian species and editing of the pre-mRNA of this protein is likely to occur in mice, rat, dog and cow as well as humans. Even though the ECS is not conserved in non-mammals, an alternative ECS has been predicted in Zebrafish with a similar structure but in a different location. The Ecs is found downstram of the editing sites.[3]
## Effects on Protein structure
These predicted editing sites result in the translation of an Arginine instead of a Glutamine at the Q/R site and an Alanine instead of a Threonine at the T/A site. These codon changes are nonsynomonous.[3] Since the editing sites are located just before a collagen like trimerization domain, editing may effect protein oligomerization. This region is also likely to be a protease domain. It is not known if the amino acid changes caused by editing could have an effect on these domains.[3] | https://www.wikidoc.org/index.php/C1QL1 | |
76f68ab8d2d4bed00b1e4d94f0ffe7df2ecbfeac | wikidoc | CAPN3 | CAPN3
Calpain-3 is a protein that in humans is encoded by the CAPN3 gene.
# Function
Calpain, a heterodimer consisting of a large and a small subunit, is a major intracellular protease, although its function has not been well established. This gene encodes a muscle-specific member of the calpain large subunit family that specifically binds to titin. Mutations in this gene are associated with limb-girdle muscular dystrophies type 2A. Alternate promoters and alternative splicing result in multiple transcript variants encoding different isoforms and some variants are ubiquitously expressed.
In melanocytic cells CAPN3 gene expression may be regulated by MITF.
# Interactions
CAPN3 has been shown to interact with Titin. | CAPN3
Calpain-3 is a protein that in humans is encoded by the CAPN3 gene.[1][2]
# Function
Calpain, a heterodimer consisting of a large and a small subunit, is a major intracellular protease, although its function has not been well established. This gene encodes a muscle-specific member of the calpain large subunit family that specifically binds to titin. Mutations in this gene are associated with limb-girdle muscular dystrophies type 2A. Alternate promoters and alternative splicing result in multiple transcript variants encoding different isoforms and some variants are ubiquitously expressed.[3]
In melanocytic cells CAPN3 gene expression may be regulated by MITF.[4]
# Interactions
CAPN3 has been shown to interact with Titin.[5][6] | https://www.wikidoc.org/index.php/CAPN3 | |
3b5b931d908b39f7eb8729ec924065d04d3755dc | wikidoc | CAPZB | CAPZB
F-actin-capping protein subunit beta, also known as CapZβ is a protein that in humans is encoded by the CAPZB gene. CapZβ functions to cap actin filaments at barbed ends in muscle and other tissues.
# Structure
CapZβ can exist as 3 unique β subunits, dependent on alternative splicing mechanisms. CapZβ1 is 31.4 kDa and 277 amino acids in length, CapZβ2 is 30.6 kDa and 272 amino acids in length, and CapZβ3 is 301 amino acids in length (N-terminal extension of 29 amino acids relative to the β2 subunit.). In contrast, the 3 α subunits arise from distinct genes. CapZ is a heterodimer composed of an α and β subunit. In muscle, capping protein α1 subunit and β1 subunit are localized at the Z-disc, and form CapZ. CapZ interacts with α-actinin, nebulette, nebulin, HSC70. at the Z-disc.
# Function
CAPZB is a member of the F-actin capping protein family. This gene encodes the beta subunit of the barbed-end actin binding protein. The protein regulates growth of the actin filament by capping the barbed end of growing actin filaments.
CapZβ functions to cap actin filaments at barbed (+) ends, thus controlling the rate of G-actin polymerization to F-actin and corresponding filament length. CapZ works in concert with tropomodulin, which caps actin at pointed ends. In muscle, the interaction of CapZ with actin is critical during myofibrilogenesis, as administration of a CapZ monoclonal antibody or expression of CapZ mutant protein disrupts actin filament formation and assembly of myofibrils. Isoforms of the CapZβ (β1 and β2) have distinct functions, as CapZβ1 anchors actin at Z-discs and CapZβ2 at intercalated discs. Overexpression of CapZβ2 (and concomitant down-regulation of CapZβ1) in mice resulted in a diseased phenotype with stunted growth, irregular gait, labored breathing and juvenile lethality. Ultrastructural measurements showed severely disrupted myofibrillar architecture. A function of CapZβ in transducing protein kinase C signaling in cardiac myocytes was illuminated by a study in skinned cardiac fibers which demonstrated that partial, transgenic reduction of CapZβ attenuated the functional effect of protein kinase C on contraction and disturbed normal PKC isoform translocation patterns following phenylephrine or endothelin-1 treatment. A later study showed that partial reduction of CapZβ was cardioprotective during ischemia-reperfusion injury, concomitant with altered PKC isoform translocation to myofilaments. Regarding the turnover of CapZβ, it was recently demonstrated that the protein turnover of CapZβ1 is in part regulated by the Bcl-2–associated athanogene, BAG3, through a mechanism involving the association between HSC70 and CapZβ1.
# Clinical Significance
There is currently little to no data available on the relationship between the CAPZB gene and human disease.
# Model organisms
Model organisms have been used in the study of CAPZB function. A conditional knockout mouse line, called Capzbtm1a(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.
Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion. Twenty three tests were carried out on mutant mice and four significant abnormalities were observed. No homozygous mutant embryos were identified during gestation, and therefore none survived until weaning. The remaining tests were carried out on heterozygous mutant adult mice and decreased circulating triglyceride levels were observed in female animals, while males displayed abnormal behaviour in an open field. | CAPZB
F-actin-capping protein subunit beta, also known as CapZβ is a protein that in humans is encoded by the CAPZB gene.[1] CapZβ functions to cap actin filaments at barbed ends in muscle and other tissues.
# Structure
CapZβ can exist as 3 unique β subunits, dependent on alternative splicing mechanisms.[2][3][4][5] CapZβ1 is 31.4 kDa and 277 amino acids in length, CapZβ2 is 30.6 kDa and 272 amino acids in length, and CapZβ3 is 301 amino acids in length (N-terminal extension of 29 amino acids relative to the β2 subunit.[3]). In contrast, the 3 α subunits arise from distinct genes.[6] CapZ is a heterodimer composed of an α and β subunit. In muscle, capping protein α1 subunit and β1 subunit are localized at the Z-disc, and form CapZ.[7] CapZ interacts with α-actinin, nebulette, nebulin, HSC70.[8] at the Z-disc.
# Function
CAPZB is a member of the F-actin capping protein family. This gene encodes the beta subunit of the barbed-end actin binding protein. The protein regulates growth of the actin filament by capping the barbed end of growing actin filaments.[1]
CapZβ functions to cap actin filaments at barbed (+) ends, thus controlling the rate of G-actin polymerization to F-actin and corresponding filament length. CapZ works in concert with tropomodulin, which caps actin at pointed ends. In muscle, the interaction of CapZ with actin is critical during myofibrilogenesis, as administration of a CapZ monoclonal antibody or expression of CapZ mutant protein disrupts actin filament formation and assembly of myofibrils.[9] Isoforms of the CapZβ (β1 and β2) have distinct functions, as CapZβ1 anchors actin at Z-discs and CapZβ2 at intercalated discs.[10][11] Overexpression of CapZβ2 (and concomitant down-regulation of CapZβ1) in mice resulted in a diseased phenotype with stunted growth, irregular gait, labored breathing and juvenile lethality. Ultrastructural measurements showed severely disrupted myofibrillar architecture.[11] A function of CapZβ in transducing protein kinase C signaling in cardiac myocytes was illuminated by a study in skinned cardiac fibers which demonstrated that partial, transgenic reduction of CapZβ attenuated the functional effect of protein kinase C on contraction and disturbed normal PKC isoform translocation patterns following phenylephrine or endothelin-1 treatment.[12] A later study showed that partial reduction of CapZβ was cardioprotective during ischemia-reperfusion injury, concomitant with altered PKC isoform translocation to myofilaments.[13] Regarding the turnover of CapZβ, it was recently demonstrated that the protein turnover of CapZβ1 is in part regulated by the Bcl-2–associated athanogene, BAG3, through a mechanism involving the association between HSC70 and CapZβ1.[8]
# Clinical Significance
There is currently little to no data available on the relationship between the CAPZB gene and human disease.
# Model organisms
Model organisms have been used in the study of CAPZB function. A conditional knockout mouse line, called Capzbtm1a(EUCOMM)Wtsi[20][21] 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.[22][23][24]
Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion.[18][25] Twenty three tests were carried out on mutant mice and four significant abnormalities were observed.[18] No homozygous mutant embryos were identified during gestation, and therefore none survived until weaning. The remaining tests were carried out on heterozygous mutant adult mice and decreased circulating triglyceride levels were observed in female animals, while males displayed abnormal behaviour in an open field.[18] | https://www.wikidoc.org/index.php/CAPZB | |
5e33b01b4c6b79f0fb04a037aaa0cedc53f89cac | wikidoc | CARD9 | CARD9
Caspase recruitment domain-containing protein 9 is an adaptor protein which in humans is encoded by the CARD9 gene.It mediates signals from pattern recognition receptors to activate pro-inflammatory and anti-inflammatory cytokines, regulating inflammation and cell apoptosis. Homozygous mutations in CARD9 are associated with defective innate immunity against yeasts, like Candida and dermatophytes.
# Function
CARD9 is a member of the CARD protein family, which is defined by the presence of a characteristic caspase-associated recruitment domain (CARD). CARD is a protein interaction domain known to participate in activation or suppression of CARD containing members of the caspase family, and thus plays an important regulatory role in cell apoptosis. This protein was identified by its selective association with the CARD domain of BCL10, a positive regulator of apoptosis and NF-κB activation.It is thought to function as a molecular scaffold for the assembly of a BCL10 signaling complex that activates NF-κB. Several alternatively spliced transcript variants have been observed, but their full-length nature is not clearly defined.
# Clinical significance
In 2006, it became clear that Card9 plays important roles within the innate immune respons against yeasts. Card9 mediates signals from so called pattern recognition receptors (Dectin-1) to downstream signalling pathways such as NF-κB and by this activates pro-inflammatory cytokines (TNF, IL-23, IL-6, IL-2) and an anti-inflammatory cytokine (IL-10) and subsequently an appropriate innate and adaptive immune response to clear an infection.
An autosomal recessive form of susceptibility to chronic mucocutaneous candidiasis was found in 2009 to be associated with homozygous mutations in CARD9.
Deep dermatophytosis and Card9 deficiency reported in an Iranian family led to its discovery in 17 people from Tunisian, Algerian, and Moroccan families with deep dermatophytosis.
CARD9 mutations have been associated with inflammatory diseases such as ankylosing spondylitis and inflammatory bowel disease (Crohn's Disease and Ulcerative Colitis).
# Model organisms
Model organisms have been used in the study of CARD9 function. A conditional knockout mouse line called Card9tm1a(EUCOMM)Hmgu 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 - in-depth bone and cartilage phenotyping | CARD9
Caspase recruitment domain-containing protein 9 is an adaptor protein which in humans is encoded by the CARD9 gene.[1][2]It mediates signals from pattern recognition receptors to activate pro-inflammatory and anti-inflammatory cytokines, regulating inflammation and cell apoptosis. Homozygous mutations in CARD9 are associated with defective innate immunity against yeasts, like Candida and dermatophytes.
# Function
CARD9 is a member of the CARD protein family, which is defined by the presence of a characteristic caspase-associated recruitment domain (CARD). CARD is a protein interaction domain known to participate in activation or suppression of CARD containing members of the caspase family, and thus plays an important regulatory role in cell apoptosis. This protein was identified by its selective association with the CARD domain of BCL10, a positive regulator of apoptosis and NF-κB activation.[3]It is thought to function as a molecular scaffold for the assembly of a BCL10 signaling complex that activates NF-κB. Several alternatively spliced transcript variants have been observed, but their full-length nature is not clearly defined.[2]
# Clinical significance
In 2006, it became clear that Card9 plays important roles within the innate immune respons against yeasts. Card9 mediates signals from so called pattern recognition receptors (Dectin-1) to downstream signalling pathways such as NF-κB and by this activates pro-inflammatory cytokines (TNF, IL-23, IL-6, IL-2) and an anti-inflammatory cytokine (IL-10) and subsequently an appropriate innate and adaptive immune response to clear an infection.[4]
An autosomal recessive form of susceptibility to chronic mucocutaneous candidiasis was found in 2009 to be associated with homozygous mutations in CARD9.[5]
Deep dermatophytosis and Card9 deficiency reported in an Iranian family led to its discovery in 17 people from Tunisian, Algerian, and Moroccan families with deep dermatophytosis.[6]
CARD9 mutations have been associated with inflammatory diseases such as ankylosing spondylitis and inflammatory bowel disease (Crohn's Disease and Ulcerative Colitis).[7][8]
# Model organisms
Model organisms have been used in the study of CARD9 function. A conditional knockout mouse line called Card9tm1a(EUCOMM)Hmgu was generated at the Wellcome Trust Sanger Institute.[9] Male and female animals underwent a standardized phenotypic screen[10] to determine the effects of deletion.[11][12][13][14] Additional screens performed: - In-depth immunological phenotyping[15] - in-depth bone and cartilage phenotyping[16] | https://www.wikidoc.org/index.php/CARD9 | |
64ade3db66fd1beaa2351f4846317cb370e452fe | wikidoc | CARKD | CARKD
Carbohydrate kinase domain containing protein (abbreviated as CARKD), encoded by CARKD gene, is a human protein of unknown function. The CARKD gene encodes proteins with a predicted mitochondrial propeptide (mCARKD), a signal peptide (spCARKD) or neither of them (cCARKD). Confocal microscopy analysis of transfected CHO (Chinese-hamster ovary) cells indicated that cCARKD remains in the cytosol, whereas mCARKD and spCARKD are targeted to the mitochondria and the endoplasmic reticulum respectively. The protein is conserved throughout many species, and has predicted orthologs through eukaryotes, bacteria, and archea.
# Structure
## Gene
Human CARKD gene has 10 exons and resides on Chromosome 13 at q34. The following genes are near CARKD on the chromosome:
- COL4A2: A2 Subunit of type IV collagen
- RAB20: Potential regulator of Connexin 43 trafficking.
- CARS2: Mitochondrial Cystienyl-tRNA Synthetase 2
- ING1: Tumor-Suppressor Protein
## Protein
This protein is part of the phosphomethylpyrimidine kinase: ribokinase / pfkB superfamily. This family is characterized by the presence of a domain shared by the family. CARKD contains a carbohydrate kinase domain (Pfam PF01256). This family is related to Pfam PF02210 and Pfam PF00294 implying that it also is a carbohydrate kinase.
## Predicted properties
The following properties of CARKD were predicted using bioinformatic analysis:
- Molecular Weight: 41.4 KDal
- Isoelectric point: 9.377
CARKD orthologs have highly variable isoelectric points.
- CARKD orthologs have highly variable isoelectric points.
- Post-translational modification: Three post-translational modifications are predicted:
Modified Phosphotyrosine Residue
Two N-Linked Glycosylation Sites
- Modified Phosphotyrosine Residue
- Two N-Linked Glycosylation Sites
- A Signal Peptide and signal peptide cleavage site was predicted.
# Function
## Tissue distribution
CARKD appears to be ubiquitously expressed at high levels. Expression data in the human protein, and the mouse ortholog, indicate its expression in almost all tissues. One peculiar expression pattern of CARKD is its differential expression through the development of oligodendrocytes. Its expression is lower in oligodendrocyte progenitor cells than in mature oligodendrocytes.
## Binding partners
The human protein apolipoprotein A-1 binding precursor (APOA1BP) was predicted to be a binding partner for CARKD. This prediction is based on co-occurrence across genomes and co-expression. In addition to these data, the orthologs of CARKD in E. coli contain a domain similar to APOA1BP. This indicates that the two proteins are likely to have originated from a common evolutionary ancestor and, according to Rosetta stone analysis theory, are likely interaction partners even in species such as humans where the two proteins are not produced as a single polypeptide.
# Clinical significance
Based on allele-specific expression of CARKD, CARKD may play a role in acute lymphoblastic leukemia. In addition, microarray data indicates that CARKD is up-regulated in Glioblastoma multiforme tumors. | CARKD
Carbohydrate kinase domain containing protein (abbreviated as CARKD), encoded by CARKD gene, is a human protein of unknown function. The CARKD gene encodes proteins with a predicted mitochondrial propeptide (mCARKD), a signal peptide (spCARKD) or neither of them (cCARKD). Confocal microscopy analysis of transfected CHO (Chinese-hamster ovary) cells indicated that cCARKD remains in the cytosol, whereas mCARKD and spCARKD are targeted to the mitochondria and the endoplasmic reticulum respectively.[2] The protein is conserved throughout many species, and has predicted orthologs through eukaryotes, bacteria, and archea.
# Structure
## Gene
Human CARKD gene has 10 exons and resides on Chromosome 13 at q34. The following genes are near CARKD on the chromosome:[3]
- COL4A2: A2 Subunit of type IV collagen
- RAB20: Potential regulator of Connexin 43 trafficking.
- CARS2: Mitochondrial Cystienyl-tRNA Synthetase 2
- ING1: Tumor-Suppressor Protein
## Protein
This protein is part of the phosphomethylpyrimidine kinase: ribokinase / pfkB superfamily. This family is characterized by the presence of a domain shared by the family.[4] CARKD contains a carbohydrate kinase domain (Pfam PF01256).[4] This family is related to Pfam PF02210 and Pfam PF00294 implying that it also is a carbohydrate kinase.
## Predicted properties
The following properties of CARKD were predicted using bioinformatic analysis:
- Molecular Weight: 41.4 KDal[5]
- Isoelectric point: 9.377[6]
CARKD orthologs have highly variable isoelectric points.[6]
- CARKD orthologs have highly variable isoelectric points.[6]
- Post-translational modification: Three post-translational modifications are predicted:
Modified Phosphotyrosine Residue[7]
Two N-Linked Glycosylation Sites[7]
- Modified Phosphotyrosine Residue[7]
- Two N-Linked Glycosylation Sites[7]
- A Signal Peptide and signal peptide cleavage site was predicted.[8]
# Function
## Tissue distribution
CARKD appears to be ubiquitously expressed at high levels. Expression data in the human protein, and the mouse ortholog, indicate its expression in almost all tissues.[9][10] One peculiar expression pattern of CARKD is its differential expression through the development of oligodendrocytes. Its expression is lower in oligodendrocyte progenitor cells than in mature oligodendrocytes.[11]
## Binding partners
The human protein apolipoprotein A-1 binding precursor (APOA1BP) was predicted to be a binding partner for CARKD.[12] This prediction is based on co-occurrence across genomes and co-expression. In addition to these data, the orthologs of CARKD in E. coli contain a domain similar to APOA1BP. This indicates that the two proteins are likely to have originated from a common evolutionary ancestor and, according to Rosetta stone analysis theory,[13] are likely interaction partners even in species such as humans where the two proteins are not produced as a single polypeptide.
# Clinical significance
Based on allele-specific expression of CARKD, CARKD may play a role in acute lymphoblastic leukemia.[14] In addition, microarray data indicates that CARKD is up-regulated in Glioblastoma multiforme tumors.[15] | https://www.wikidoc.org/index.php/CARKD |
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