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407a5d8cca74b50e1544a3522315d5cb971d02de	wikidoc	Thigh	Thigh In humans the thigh is the area between the pelvis and buttocks and the knee. Anatomically, it is part of the lower limb. The single bone in the thigh is called the femur. This bone is very thick and strong (due to the high proportion of cortical bone), and forms a ball and socket joint at the hip, and a condylar joint at the knee. # Fascial compartments In cross-section, the thigh is divided up into three fascial compartments. These compartments use the femur as an axis, and are separated by tough connective tissue membranes (or septa). Each of these compartments has its own blood and nerve supply, and contains a different group of muscles. - Medial fascial compartment of thigh - Posterior fascial compartment of thigh - Anterior fascial compartment of thigh # Blood vessels The arterial supply is by the femoral artery and the obturator system. The lymphatic drainage closely follows the arterial supply. The deep venous system of the thigh consists of the femoral vein, the proximal part of the popliteal vein, and various smaller vessels; these are the site of proximal deep venous thrombosis. The venae perfortantes connect the deep and the superficial system, which consists of the saphenous veins (the site of varicose veins). # Thigh weakness Thigh weakness can result in a positive Gower's sign on physical examination. cs:Stehno de:Oberschenkel eo:Femuro id:Paha it:coscia (anatomia) he:ירך nl:Dij no:Lår sv:Lår yi:פולקע	Thigh Template:Infobox Anatomy Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] In humans the thigh is the area between the pelvis and buttocks and the knee. Anatomically, it is part of the lower limb. The single bone in the thigh is called the femur. This bone is very thick and strong (due to the high proportion of cortical bone), and forms a ball and socket joint at the hip, and a condylar joint at the knee. # Fascial compartments In cross-section, the thigh is divided up into three fascial compartments. These compartments use the femur as an axis, and are separated by tough connective tissue membranes (or septa). Each of these compartments has its own blood and nerve supply, and contains a different group of muscles. - Medial fascial compartment of thigh - Posterior fascial compartment of thigh - Anterior fascial compartment of thigh # Blood vessels The arterial supply is by the femoral artery and the obturator system. The lymphatic drainage closely follows the arterial supply. The deep venous system of the thigh consists of the femoral vein, the proximal part of the popliteal vein, and various smaller vessels; these are the site of proximal deep venous thrombosis. The venae perfortantes connect the deep and the superficial system, which consists of the saphenous veins (the site of varicose veins). # Thigh weakness Thigh weakness can result in a positive Gower's sign on physical examination. Template:Human anatomical features Template:Lower limb general cs:Stehno de:Oberschenkel eo:Femuro id:Paha it:coscia (anatomia) he:ירך nl:Dij no:Lår sv:Lår yi:פולקע Template:WH Template:WikiDoc Sources	https://www.wikidoc.org/index.php/Thigh
24cf7d9933b106a7a1f57f023cb1de63f89f674a	wikidoc	Thyme	Thyme Thyme (Thymus) (pronounced "time") is a genus of about 350 species of aromatic perennial herbaceous plants and sub-shrubs to 40 cm tall, in the family Lamiaceae and native to Europe, North Africa and Asia. A number of species have different chemotypes. The stems tend to be narrow or even wiry; the leaves are evergreen in most species, arranged in opposite pairs, oval, entire, and small, 4-20 mm long. The flowers are in dense terminal heads, with an uneven calyx, with the upper lip three-lobed, and the lower cleft; the corolla is tubular, 4-10 mm long, and white, pink or purple. Thymus species are used as food plants by the larvae of some Lepidoptera insect species including Chionodes distinctella and the Coleophora case-bearers C. lixella, C. niveicostella, C. serpylletorum and C. struella (the latter three feed exclusively on Thymus). ## History Ancient Egyptians used thyme in embalming. The ancient Greeks used it in their baths and burnt it as incense in their temples, believing that thyme was a source of courage. It was thought that the spread of thyme throughout Europe was thanks to the Romans, as they used it to purify their rooms. In the European Middle Ages, the herb was placed beneath pillows to aid sleep and ward off nightmares. (Huxley 1992). In this period, women would also often give knights and warriors gifts that included thyme leaves as it was believed to bring courage to the bearer. Thyme was also used as incense and placed on coffins during funerals as it was supposed to assure passage into the next life. ## Cultivation Thyme is widely cultivated as a grown for its strong flavour, which is due to its content of thymol. Thyme likes a hot sunny location with good-draining soil. It is planted in the spring and thereafter grows as a perennial. It can be propagated by seed, cuttings, or by dividing rooted sections of the plant. It tolerates drought well. Thyme retains its flavour on drying better than many other herbs. ## Culinary use Thyme is used most widely in cooking. Thyme is a basic ingredient in French and Italian cuisines, and in those derived from them. It is also widely used in Lebanese and Caribbean cuisines. Thyme is often used to flavour meats, soups and stews. It has a particular affinity to and is often used as a primary flavour with lamb, tomatoes and eggs. Thyme, while flavourful, does not overpower and blends well with other herbs and spices. In French cuisine, along with bay and parsley it is a common component of the bouquet garni, and of herbes de Provence. In some Middle Eastern countries, the condiment za'atar contains thyme as a vital ingredient. ### Fresh, Powdered, and Dry Thyme is sold both fresh and dried. The fresh form is more flavourful but also less convenient; storage life is rarely more than a week. While summer-seasonal, fresh thyme is often available year-round. Fresh thyme is commonly sold in bunches of sprigs. A sprig is a single stem snipped from the plant. It is composed of a woody stem with paired leaf or flower clusters ("leaves") spaced ½ to 1" apart. A recipe may measure thyme by the bunch (or fraction thereof), or by the sprig, or by the tablespoon or teaspoon. If the recipe does not specify fresh or dried, assume that it means fresh. Depending on how it is used in a dish, the whole sprig may be used (e.g. in a bouquet garni), or the leaves removed and the stems discarded. Usually when a recipe specifies 'bunch' or 'sprig' it means the whole form; when it specifies spoons it means the leaves. It is perfectly acceptable to substitute dried for whole thyme. Leaves may be removed from stems either by scraping with the back of a knife, or by pulling through the fingers or tines of a fork. Leaves are often chopped. Thyme retains its flavour on drying better than many other herbs. Dried, and especially powdered thyme occupies less space than fresh, so less of it is required when substituted in a recipe. As a rule of thumb, use one third as much dried as fresh thyme - a little less if it is ground. Substitution is often more complicated than that because recipes can specify sprigs and sprigs can vary in yield of leaves. Assuming a 4" sprig (they are often somewhat longer), estimate that 6 sprigs will yield one tablespoon of leaves. The dried equivalent is 1:3, so substitute 1 teaspoon of dried or ¾ tsp of ground thyme for 6 small sprigs. As with bay, thyme is slow to release its flavours so it is usually added early in the cooking process. ## Medicinal Use The essential oil of common thyme (Thymus vulgaris) is made up of 20-55% thymol. Thymol, an antiseptic, is the main active ingredient in Listerine mouthwash. Before the advent of modern antibiotics, it was used to medicate bandages. It has also been shown to be effective against the fungus that commonly infects toenails. A tea made by infusing the herb in water can be used for cough and bronchitis. Medicinally thyme is used for respiratory infections in the form of a tincture, tisane, salve, syrup or by steam inhalation. Because it is antiseptic, thyme boiled in water and cooled is very effective against inflammation of the throat when gargled 3 times a day. The inflammation will normally disappear in 2 - 5 days. Other infections and wounds can be dripped with thyme that has been boiled in water and cooled. In traditional Jamaican childbirth practice, thyme tea is given to the mother after delivery of the baby. Its oxytocin-like effect causes uterine contractions and more rapid delivery of the placenta but this was said by Sheila Kitzinger to cause an increased prevalence of retained placenta. ## Important species Thymus vulgaris (Common Thyme or Garden Thyme) is a commonly used culinary herb. It also has medicinal uses. Common thyme is a Mediterranean perennial which is best suited to well-drained soils and enjoys full sun. Thymus herba-barona (Caraway Thyme) is used both as a culinary herb and a groundcover, and has a strong caraway scent due to the chemical carvone. Thymus × citriodorus (Citrus Thyme; hybrid T. pulegioides × T. vulgaris) is also a popular culinary herb, with cultivars selected with flavours of various Citrus fruit (lemon thyme, etc.) Thymus pseudolanuginosus (Woolly Thyme) is not a culinary herb, but is grown as a ground cover. Thymus serpyllum (Wild Thyme) is an important nectar source plant for honeybees. All thyme species are nectar sources, but wild thyme covers large areas of droughty, rocky soils in southern Europe (Greece is especially famous for wild thyme honey) and North Africa, as well as in similar landscapes in the Berkshire Mountains and Catskill Mountains of the northeastern US. ## Various cultivars There are a number of different cultivars of thyme with established or growing popularity, including: - Lemon thyme -- actually smells lemony - Variegated lemon thyme -- with bi-color leaves - Orange thyme -- an unusually low-growing, ground cover thyme that smells like orange - Creeping thyme -- the lowest-growing of the widely used thymes, good for walkways - Silver thyme -- white/cream variegated - English thyme -- the most common - Summer thyme -- unusually strong flavor # Notes - ↑ Huxley, A., ed. (1992). New RHS Dictionary of Gardening. Macmillan. - ↑ #Garden%20Thyme Herb File. Global Garden. - ↑ Thymus Vulgaris. PDR for Herbal Medicine. Montvale, NJ: Medical Economics Company. p. 1184. - ↑ Pierce, Andrea. 1999. American Pharmaceutical Association Practical Guide to Natural Medicines. New York: Stonesong Press. P. 338-340. - ↑ Grieve, Maud (Mrs.). Thyme. A Modern Herbal. Hypertext version of the 1931 edition. Accessed: December 14, 2006. - ↑ Ramsewak RS, et al. In vitro antagonistic activity of monoterpenes and their mixtures against 'toe nail fungus' pathogens. Phytother Res. 2003 Apr;17(4):376-9. - ↑ Thymus Vulgaris. PDR for Herbal Medicine. Montvale, NJ: Medical Economics Company. p. 1184.	Thyme Thyme (Thymus) (pronounced "time") is a genus of about 350 species of aromatic perennial herbaceous plants and sub-shrubs to 40 cm tall, in the family Lamiaceae and native to Europe, North Africa and Asia. A number of species have different chemotypes. The stems tend to be narrow or even wiry; the leaves are evergreen in most species, arranged in opposite pairs, oval, entire, and small, 4-20 mm long. The flowers are in dense terminal heads, with an uneven calyx, with the upper lip three-lobed, and the lower cleft; the corolla is tubular, 4-10 mm long, and white, pink or purple. Thymus species are used as food plants by the larvae of some Lepidoptera insect species including Chionodes distinctella and the Coleophora case-bearers C. lixella, C. niveicostella, C. serpylletorum and C. struella (the latter three feed exclusively on Thymus). ## History Ancient Egyptians used thyme in embalming. The ancient Greeks used it in their baths and burnt it as incense in their temples, believing that thyme was a source of courage. It was thought that the spread of thyme throughout Europe was thanks to the Romans, as they used it to purify their rooms. In the European Middle Ages, the herb was placed beneath pillows to aid sleep and ward off nightmares. (Huxley 1992). In this period, women would also often give knights and warriors gifts that included thyme leaves as it was believed to bring courage to the bearer. Thyme was also used as incense and placed on coffins during funerals as it was supposed to assure passage into the next life.[1] ## Cultivation Thyme is widely cultivated as a grown for its strong flavour, which is due to its content of thymol.[2] Thyme likes a hot sunny location with good-draining soil. It is planted in the spring and thereafter grows as a perennial. It can be propagated by seed, cuttings, or by dividing rooted sections of the plant. It tolerates drought well.[3] Thyme retains its flavour on drying better than many other herbs. ## Culinary use Thyme is used most widely in cooking. Thyme is a basic ingredient in French and Italian cuisines, and in those derived from them. It is also widely used in Lebanese and Caribbean cuisines. Thyme is often used to flavour meats, soups and stews. It has a particular affinity to and is often used as a primary flavour with lamb, tomatoes and eggs. Thyme, while flavourful, does not overpower and blends well with other herbs and spices. In French cuisine, along with bay and parsley it is a common component of the bouquet garni, and of herbes de Provence. In some Middle Eastern countries, the condiment za'atar contains thyme as a vital ingredient. ### Fresh, Powdered, and Dry Thyme is sold both fresh and dried. The fresh form is more flavourful but also less convenient; storage life is rarely more than a week. While summer-seasonal, fresh thyme is often available year-round. Fresh thyme is commonly sold in bunches of sprigs. A sprig is a single stem snipped from the plant. It is composed of a woody stem with paired leaf or flower clusters ("leaves") spaced ½ to 1" apart. A recipe may measure thyme by the bunch (or fraction thereof), or by the sprig, or by the tablespoon or teaspoon. If the recipe does not specify fresh or dried, assume that it means fresh. Depending on how it is used in a dish, the whole sprig may be used (e.g. in a bouquet garni), or the leaves removed and the stems discarded. Usually when a recipe specifies 'bunch' or 'sprig' it means the whole form; when it specifies spoons it means the leaves. It is perfectly acceptable to substitute dried for whole thyme. Leaves may be removed from stems either by scraping with the back of a knife, or by pulling through the fingers or tines of a fork. Leaves are often chopped. Thyme retains its flavour on drying better than many other herbs. Dried, and especially powdered thyme occupies less space than fresh, so less of it is required when substituted in a recipe. As a rule of thumb, use one third as much dried as fresh thyme - a little less if it is ground. Substitution is often more complicated than that because recipes can specify sprigs and sprigs can vary in yield of leaves. Assuming a 4" sprig (they are often somewhat longer), estimate that 6 sprigs will yield one tablespoon of leaves. The dried equivalent is 1:3, so substitute 1 teaspoon of dried or ¾ tsp of ground thyme for 6 small sprigs. [4] As with bay, thyme is slow to release its flavours so it is usually added early in the cooking process. ## Medicinal Use The essential oil of common thyme (Thymus vulgaris) is made up of 20-55% thymol.[5] Thymol, an antiseptic, is the main active ingredient in Listerine mouthwash.[6] Before the advent of modern antibiotics, it was used to medicate bandages.[7] It has also been shown to be effective against the fungus that commonly infects toenails.[8] A tea made by infusing the herb in water can be used for cough and bronchitis.[9] Medicinally thyme is used for respiratory infections in the form of a tincture, tisane, salve, syrup or by steam inhalation[citation needed]. Because it is antiseptic, thyme boiled in water and cooled is very effective against inflammation of the throat when gargled 3 times a day.[citation needed] The inflammation will normally disappear in 2 - 5 days. Other infections and wounds can be dripped with thyme that has been boiled in water and cooled.[citation needed] In traditional Jamaican childbirth practice, thyme tea is given to the mother after delivery of the baby. Its oxytocin-like effect causes uterine contractions and more rapid delivery of the placenta but this was said by Sheila Kitzinger to cause an increased prevalence of retained placenta. ## Important species Thymus vulgaris (Common Thyme or Garden Thyme) is a commonly used culinary herb. It also has medicinal uses. Common thyme is a Mediterranean perennial which is best suited to well-drained soils and enjoys full sun. Thymus herba-barona (Caraway Thyme) is used both as a culinary herb and a groundcover, and has a strong caraway scent due to the chemical carvone. Thymus × citriodorus (Citrus Thyme; hybrid T. pulegioides × T. vulgaris) is also a popular culinary herb, with cultivars selected with flavours of various Citrus fruit (lemon thyme, etc.) Thymus pseudolanuginosus (Woolly Thyme) is not a culinary herb, but is grown as a ground cover. Thymus serpyllum (Wild Thyme) is an important nectar source plant for honeybees. All thyme species are nectar sources, but wild thyme covers large areas of droughty, rocky soils in southern Europe (Greece is especially famous for wild thyme honey) and North Africa, as well as in similar landscapes in the Berkshire Mountains and Catskill Mountains of the northeastern US. ## Various cultivars There are a number of different cultivars of thyme with established or growing popularity, including: - Lemon thyme -- actually smells lemony - Variegated lemon thyme -- with bi-color leaves - Orange thyme -- an unusually low-growing, ground cover thyme that smells like orange - Creeping thyme -- the lowest-growing of the widely used thymes, good for walkways - Silver thyme -- white/cream variegated - English thyme -- the most common - Summer thyme -- unusually strong flavor # Notes - ↑ [1] - ↑ Huxley, A., ed. (1992). New RHS Dictionary of Gardening. Macmillan. - ↑ http://www.global-garden.com.au/gardenherbs5.htm#Garden%20Thyme Herb File. Global Garden. - ↑ http://www.apinchof.com/freshordriedqanda.htm - ↑ Thymus Vulgaris. PDR for Herbal Medicine. Montvale, NJ: Medical Economics Company. p. 1184. - ↑ Pierce, Andrea. 1999. American Pharmaceutical Association Practical Guide to Natural Medicines. New York: Stonesong Press. P. 338-340. - ↑ Grieve, Maud (Mrs.). Thyme. A Modern Herbal. Hypertext version of the 1931 edition. Accessed: December 14, 2006. http://botanical.com/botanical/mgmh/t/thygar16.html - ↑ Ramsewak RS, et al. In vitro antagonistic activity of monoterpenes and their mixtures against 'toe nail fungus' pathogens. Phytother Res. 2003 Apr;17(4):376-9. - ↑ Thymus Vulgaris. PDR for Herbal Medicine. Montvale, NJ: Medical Economics Company. p. 1184.	https://www.wikidoc.org/index.php/Thyme
6338edb2709300ea035c3e3332c5db6e4688f9f5	wikidoc	Tinea	Tinea # Overview Dermatophytosis are a group of mycosis infections of the skin caused by parasitic fungi (dermatophytes). # Presentations Infections on the body may give rise to typical enlarging raised red rings of ringworm, infection on the skin of the feet may cause athlete's foot and in the groin jock itch. Involvement of the nails is termed onychomycosis, and they may thicken, discolour, and finally crumble and fall off. They are common in most adult people, with up to 20 percent of the population having one of these infections at any given moment. It tends to getting worse during summer and then symptoms alleviated during the winter. # Types A number of different species of fungi are involved. Dermatophytes of the genera Trichophyton and Microsporum are the most common causative agents. These fungi attack various parts of the body and lead to the following conditions: - Dermatophytosis Tinea pedis (athlete's foot) affects the feet Tinea unguinum affects the fingernails and toenails Tinea corporis affects the arms, legs, and trunk with ringworm Tinea cruris (jock itch) affects the groin area Tinea manuum affects the hands and palm area Tinea capitis affects the scalp Tinea barbae affects facial hair Tinea faciei (face fungus) affects the face - Tinea pedis (athlete's foot) affects the feet - Tinea unguinum affects the fingernails and toenails - Tinea corporis affects the arms, legs, and trunk with ringworm - Tinea cruris (jock itch) affects the groin area - Tinea manuum affects the hands and palm area - Tinea capitis affects the scalp - Tinea barbae affects facial hair - Tinea faciei (face fungus) affects the face - Other superficial mycoses Tinea versicolor Tinea nigra - Tinea versicolor - Tinea nigra de:Dermatophytose	Tinea Template:Seealso For patient information click here Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] # Overview Dermatophytosis are a group of mycosis infections of the skin caused by parasitic fungi (dermatophytes). # Presentations Infections on the body may give rise to typical enlarging raised red rings of ringworm, infection on the skin of the feet may cause athlete's foot and in the groin jock itch. Involvement of the nails is termed onychomycosis, and they may thicken, discolour, and finally crumble and fall off. They are common in most adult people, with up to 20 percent of the population having one of these infections at any given moment. It tends to getting worse during summer and then symptoms alleviated during the winter. # Types A number of different species of fungi are involved. Dermatophytes of the genera Trichophyton and Microsporum are the most common causative agents. These fungi attack various parts of the body and lead to the following conditions: - Dermatophytosis Tinea pedis (athlete's foot) affects the feet Tinea unguinum affects the fingernails and toenails Tinea corporis affects the arms, legs, and trunk with ringworm Tinea cruris (jock itch) affects the groin area Tinea manuum affects the hands and palm area Tinea capitis affects the scalp Tinea barbae affects facial hair Tinea faciei (face fungus) affects the face - Tinea pedis (athlete's foot) affects the feet - Tinea unguinum affects the fingernails and toenails - Tinea corporis affects the arms, legs, and trunk with ringworm - Tinea cruris (jock itch) affects the groin area - Tinea manuum affects the hands and palm area - Tinea capitis affects the scalp - Tinea barbae affects facial hair - Tinea faciei (face fungus) affects the face - Other superficial mycoses Tinea versicolor Tinea nigra - Tinea versicolor - Tinea nigra Template:Mycoses de:Dermatophytose Template:WikiDoc Sources	https://www.wikidoc.org/index.php/Tinea
af282be40a79f679490ba5d512a26771a09fef3f	wikidoc	Titer	Titer # Overview A titer (or titre) is the unit in which the analytical detection of many substances is expressed. It is the result of a titration. Generally, the test is performed on an undiluted sample, and then repeated when the sample is mixed with 100% water, saline, or other diluent in repeated steps (a serial dilution). If the test is still positive, then high titers of the detected substance are said to be present. Many tests are positive when performed on an undiluted sample, but rapidly become negative after repeated dilution. These tests may only be of real significance if the titer is high, while lacking this significance when performed on the raw sample. A control substance may be tested alongside the sample, and/or statistical methods are used to distinguish positive from negative results. Some samples may actually give stronger reactions as they are diluted with a diluent. As further dilutions are made the reactions become less pronounced and eventually cease as the original sample is diluted to the point of no reaction. This is referred to as a prozone phenomenon. Titers are expressed in their highest positive dilution, e.g. 1:1, 1:2, 1:4, 1:8 or 1:1, 1:10, 1:100, 1:1000 where the second number is always a power of the dilution factor (e.g. 2x, 10x). Sometimes, the sample is diluted from the outset, leading to different multiplers with a similar exponential increment (e.g. 1:20, 1:40, 1:80, 1:160, 1:320).	Titer # Overview A titer (or titre) is the unit in which the analytical detection of many substances is expressed. It is the result of a titration. Generally, the test is performed on an undiluted sample, and then repeated when the sample is mixed with 100% water, saline, or other diluent in repeated steps (a serial dilution). If the test is still positive, then high titers of the detected substance are said to be present. Many tests are positive when performed on an undiluted sample, but rapidly become negative after repeated dilution. These tests may only be of real significance if the titer is high, while lacking this significance when performed on the raw sample. A control substance may be tested alongside the sample, and/or statistical methods are used to distinguish positive from negative results. Some samples may actually give stronger reactions as they are diluted with a diluent. As further dilutions are made the reactions become less pronounced and eventually cease as the original sample is diluted to the point of no reaction. This is referred to as a prozone phenomenon. Titers are expressed in their highest positive dilution, e.g. 1:1, 1:2, 1:4, 1:8 or 1:1, 1:10, 1:100, 1:1000 where the second number is always a power of the dilution factor (e.g. 2x, 10x). Sometimes, the sample is diluted from the outset, leading to different multiplers with a similar exponential increment (e.g. 1:20, 1:40, 1:80, 1:160, 1:320).	https://www.wikidoc.org/index.php/Titer
fff8db017dd3f0f12c6de19ffeb59047f404b1fa	wikidoc	Titin	Titin Titin /ˈtaɪtɪn/, also known as connectin, is a protein that, in humans, is encoded by the TTN gene. Titin is a giant protein, greater than 1 µm in length, that functions as a molecular spring which is responsible for the passive elasticity of muscle. It is composed of 244 individually folded protein domains connected by unstructured peptide sequences. These domains unfold when the protein is stretched and refold when the tension is removed. Titin is important in the contraction of striated muscle tissues. It connects the Z line to the M line in the sarcomere. The protein contributes to force transmission at the Z line and resting tension in the I band region. It limits the range of motion of the sarcomere in tension, thus contributing to the passive stiffness of muscle. Variations in the sequence of titin between different types of muscle (e.g., cardiac or skeletal) have been correlated with differences in the mechanical properties of these muscles. Titin is the third most abundant protein in muscle (after myosin and actin), and an adult human contains approximately 0.5 kg of titin. With its length of ~27,000 to ~33,000 amino acids (depending on the splice isoform), titin is the largest known protein. Furthermore, the gene for titin contains the largest number of exons (363) discovered in any single gene, as well as the longest single exon (17,106 bp). # Discovery Reiji Natori in 1954 was the first to propose an elastic structure in muscle fiber to account for the return to the resting state when muscles are stretched and then released. In 1977, Koscak Maruyama and coworkers isolated an elastic protein from muscle fiber, which they called connectin. Two years later, Kuan Wang and coworkers identified a doublet band on electrophoresis gel corresponding to a high molecular weight elastic protein, which they named titin. Siegfried Labeit in 1990 isolated a partial cDNA clone of titin. In 1995, Labeit and Bernhard Kolmerer determined the cDNA sequence of human cardiac titin. Labeit and colleagues in 2001 determined the complete sequence of the human titin gene. # Genomics The human gene encoding for titin is located on the long arm of chromosome 2 and contains 363 exons, which together code for 38,138 residues (4200 kDa). Within the gene are found a large number of PEVK (proline-glutamate-valine-lysine -abundant structural motifs) exons 84 to 99 nucleotides in length which code for conserved 28- to 33-residue motifs which may represent structural units of the titin PEVK spring. The number of PEVK motifs in the titin gene appears to have increased during evolution, apparently modifying the genomic region responsible for titin’s spring properties. # Isoforms A number of titin isoforms are produced in different striated muscle tissues as a result of alternative splicing. All but one of these isoforms are in the range of ~27,000 to ~36,000 amino acid residues in length. The exception is the small cardiac novex-3 isoform which is only 5,604 amino acid residues in length. The following table lists the known titin isoforms: # Structure Titin is the largest known protein; its human variant consists of 34,350 amino acids, with the molecular weight of the mature "canonical" isoform of the protein being approximately 3,816,188.13 Da. Its mouse homologue is even larger, comprising 35,213 amino acids with a MW of 3,906,487.6 Da. It has a theoretical isoelectric point of 6.01. The protein's empirical chemical formula is C169,719H270,466N45,688O52,238S911. It has a theoretical instability index (II) of 42.41, classifying the protein as unstable. The protein's in vivo half-life, the time it takes for half of the amount of protein in a cell to break down after its synthesis in the cell, is predicted to be approximately 30 hours (in mammalian reticulocytes). The titin protein is located between the myosin thick filament and the Z disk. Titin consists primarily of a linear array of two types of modules, also referred to as protein domains (244 copies in total): type I fibronectin type III domain (132 copies) and type II immunoglobulin domain (112 copies). However, the exact number of these domains is different in different species. This linear array is further organized into two regions: - N-terminal I-band: acts as the elastic part of the molecule and is composed mainly of type II modules. More specifically the I-band contains two regions of tandem type II immunoglobulin domains on either side of a PEVK region which is rich in proline (P), glutamate (E), valine (V) and lysine (K). - C-terminal A-band: is thought to act as a protein-ruler and is composed of alternating type I and II modules with super-repeat segments. These have been shown to align to the 43 nm axial repeats of myosin thick filaments with immunoglobulin domains correlating to myosin crowns. The C-terminal region also contains a serine kinase domain that is primarily known for adapting the muscle to mechanical strain. It is “stretch-sensitive” and helps repair overstretching of the sarcomere. The elasticity of the PEVK region has both entropic and enthalpic contributions and is characterized by a polymer persistence length and a stretch modulus. At low to moderate extensions PEVK elasticity can be modeled with a standard worm-like chain (WLC) model of entropic elasticity. At high extensions PEVK stretching can be modeled with a modified WLC model that incorporates enthalpic elasticity. The difference between low-and high- stretch elasticity is due to electrostatic stiffening and hydrophobic effects. # Evolution The titin domains have evolved from a common ancestor through many gene duplication events. Domain duplication was facilitated by the fact that most domains are encoded by single exons. Titin has homologs in invertebrates, such as twitchin and projectin, which also contain Ig and FNIII repeats and a protein kinase domain. The gene duplication events took place independently but were from the same ancestral Ig and FNIII domains. It is said that the protein titin was the first to diverge out of the family. # Function Titin is a large abundant protein of striated muscle. Titin's primary functions are to stabilize the thick filament, center it between the thin filaments, prevent overstretching of the sarcomere, and to recoil the sarcomere like a spring after it is stretched. An N-terminal Z-disc region and a C-terminal M-line region bind to the Z-line and M-line of the sarcomere, respectively, so that a single titin molecule spans half the length of a sarcomere. Titin also contains binding sites for muscle-associated proteins so it serves as an adhesion template for the assembly of contractile machinery in muscle cells. It has also been identified as a structural protein for chromosomes. Considerable variability exists in the I-band, the M-line and the Z-disc regions of titin. Variability in the I-band region contributes to the differences in elasticity of different titin isoforms and, therefore, to the differences in elasticity of different muscle types. Of the many titin variants identified, five are described with complete transcript information available. Titin interacts with many sarcomeric proteins including: - Z line region: telethonin and alpha-actinin - I band region: calpain-3 and obscurin - M line region: myosin-binding protein C, calmodulin 1, CAPN3, and MURF1 # Clinical relevance Mutations anywhere within the unusually long sequence of this gene can cause premature stop codons or other defects. Titin mutations are associated with hereditary myopathy with early respiratory failure, early-onset myopathy with fatal cardiomyopathy, core myopathy with heart disease, centronuclear myopathy, limb-girdle muscular dystrophy type 2J, familial dilated cardiomyopathy 9, hypertrophic cardiomyopathy and tibial muscular dystrophy. Further research also suggests that no genetically linked form of any dystrophy or myopathy can be safely excluded from being caused by a mutation on the TTN gene. Truncating mutations in dilated cardiomyopathy patients are most commonly found in the A region; although truncations in the upstream I region might be expected to prevent translation of the A region entirely, alternative splicing creates some transcripts that do not encounter the premature stop codon, ameliorating its effect. Autoantibodies to titin are produced in patients with the autoimmune disease scleroderma. # Interactions Titin has been shown to interact with: - ANK1, - ANKRD1, - ANKRD23 - CAPN3, - FHL2, - OBSCN, - TCAP, and - TRIM63. # Linguistic significance The name titin is derived from the Greek Titan (a giant deity, anything of great size). As the largest known protein, titin also has the longest IUPAC name of a protein. The full chemical name of the human canonical form of titin, which starts methionyl... and ends ...isoleucine, contains 189,819 letters and is sometimes stated to be the longest word in the English language, or of any language. However, lexicographers regard generic names of chemical compounds as verbal formulae rather than English words. The full word can be found here on Wiktionary.	Titin Titin /ˈtaɪtɪn/, also known as connectin, is a protein that, in humans, is encoded by the TTN gene.[1][2] Titin is a giant protein, greater than 1 µm in length,[3] that functions as a molecular spring which is responsible for the passive elasticity of muscle. It is composed of 244 individually folded protein domains connected by unstructured peptide sequences.[4] These domains unfold when the protein is stretched and refold when the tension is removed.[5] Titin is important in the contraction of striated muscle tissues. It connects the Z line to the M line in the sarcomere. The protein contributes to force transmission at the Z line and resting tension in the I band region.[6] It limits the range of motion of the sarcomere in tension, thus contributing to the passive stiffness of muscle. Variations in the sequence of titin between different types of muscle (e.g., cardiac or skeletal) have been correlated with differences in the mechanical properties of these muscles.[1][7] Titin is the third most abundant protein in muscle (after myosin and actin), and an adult human contains approximately 0.5 kg of titin.[8] With its length of ~27,000 to ~33,000 amino acids (depending on the splice isoform), titin is the largest known protein.[9] Furthermore, the gene for titin contains the largest number of exons (363) discovered in any single gene,[10] as well as the longest single exon (17,106 bp). # Discovery Reiji Natori in 1954 was the first to propose an elastic structure in muscle fiber to account for the return to the resting state when muscles are stretched and then released.[11] In 1977, Koscak Maruyama and coworkers isolated an elastic protein from muscle fiber, which they called connectin.[12] Two years later, Kuan Wang and coworkers identified a doublet band on electrophoresis gel corresponding to a high molecular weight elastic protein, which they named titin.[13][14] Siegfried Labeit in 1990 isolated a partial cDNA clone of titin.[2] In 1995, Labeit and Bernhard Kolmerer determined the cDNA sequence of human cardiac titin.[4] Labeit and colleagues in 2001 determined the complete sequence of the human titin gene.[10][15] # Genomics The human gene encoding for titin is located on the long arm of chromosome 2 and contains 363 exons, which together code for 38,138 residues (4200 kDa).[10] Within the gene are found a large number of PEVK (proline-glutamate-valine-lysine -abundant structural motifs) exons 84 to 99 nucleotides in length which code for conserved 28- to 33-residue motifs which may represent structural units of the titin PEVK spring. The number of PEVK motifs in the titin gene appears to have increased during evolution, apparently modifying the genomic region responsible for titin’s spring properties.[16] # Isoforms A number of titin isoforms are produced in different striated muscle tissues as a result of alternative splicing.[17] All but one of these isoforms are in the range of ~27,000 to ~36,000 amino acid residues in length. The exception is the small cardiac novex-3 isoform which is only 5,604 amino acid residues in length. The following table lists the known titin isoforms: # Structure Titin is the largest known protein; its human variant consists of 34,350 amino acids, with the molecular weight of the mature "canonical" isoform of the protein being approximately 3,816,188.13 Da.[18] Its mouse homologue is even larger, comprising 35,213 amino acids with a MW of 3,906,487.6 Da.[19] It has a theoretical isoelectric point of 6.01.[18] The protein's empirical chemical formula is C169,719H270,466N45,688O52,238S911.[18] It has a theoretical instability index (II) of 42.41, classifying the protein as unstable.[18] The protein's in vivo half-life, the time it takes for half of the amount of protein in a cell to break down after its synthesis in the cell, is predicted to be approximately 30 hours (in mammalian reticulocytes).[17] The titin protein is located between the myosin thick filament and the Z disk.[21] Titin consists primarily of a linear array of two types of modules, also referred to as protein domains (244 copies in total): type I fibronectin type III domain (132 copies) and type II immunoglobulin domain (112 copies).[8] [4] However, the exact number of these domains is different in different species. This linear array is further organized into two regions: - N-terminal I-band: acts as the elastic part of the molecule and is composed mainly of type II modules. More specifically the I-band contains two regions of tandem type II immunoglobulin domains on either side of a PEVK region which is rich in proline (P), glutamate (E), valine (V) and lysine (K).[21] - C-terminal A-band: is thought to act as a protein-ruler and is composed of alternating type I and II modules with super-repeat segments. These have been shown to align to the 43 nm axial repeats of myosin thick filaments with immunoglobulin domains correlating to myosin crowns.[22] The C-terminal region also contains a serine kinase domain[23][24] that is primarily known for adapting the muscle to mechanical strain.[25] It is “stretch-sensitive” and helps repair overstretching of the sarcomere.[26] The elasticity of the PEVK region has both entropic and enthalpic contributions and is characterized by a polymer persistence length and a stretch modulus.[28] At low to moderate extensions PEVK elasticity can be modeled with a standard worm-like chain (WLC) model of entropic elasticity. At high extensions PEVK stretching can be modeled with a modified WLC model that incorporates enthalpic elasticity. The difference between low-and high- stretch elasticity is due to electrostatic stiffening and hydrophobic effects. # Evolution The titin domains have evolved from a common ancestor through many gene duplication events.[29] Domain duplication was facilitated by the fact that most domains are encoded by single exons. Titin has homologs in invertebrates, such as twitchin and projectin, which also contain Ig and FNIII repeats and a protein kinase domain.[26] The gene duplication events took place independently but were from the same ancestral Ig and FNIII domains. It is said that the protein titin was the first to diverge out of the family.[24] # Function Titin is a large abundant protein of striated muscle. Titin's primary functions are to stabilize the thick filament, center it between the thin filaments, prevent overstretching of the sarcomere, and to recoil the sarcomere like a spring after it is stretched.[30] An N-terminal Z-disc region and a C-terminal M-line region bind to the Z-line and M-line of the sarcomere, respectively, so that a single titin molecule spans half the length of a sarcomere. Titin also contains binding sites for muscle-associated proteins so it serves as an adhesion template for the assembly of contractile machinery in muscle cells. It has also been identified as a structural protein for chromosomes.[31][32] Considerable variability exists in the I-band, the M-line and the Z-disc regions of titin. Variability in the I-band region contributes to the differences in elasticity of different titin isoforms and, therefore, to the differences in elasticity of different muscle types. Of the many titin variants identified, five are described with complete transcript information available.[1][2] Titin interacts with many sarcomeric proteins including:[10] - Z line region: telethonin and alpha-actinin - I band region: calpain-3 and obscurin - M line region: myosin-binding protein C, calmodulin 1, CAPN3, and MURF1 # Clinical relevance Mutations anywhere within the unusually long sequence of this gene can cause premature stop codons or other defects. Titin mutations are associated with hereditary myopathy with early respiratory failure, early-onset myopathy with fatal cardiomyopathy, core myopathy with heart disease, centronuclear myopathy, limb-girdle muscular dystrophy type 2J, familial dilated cardiomyopathy 9,[6][33] hypertrophic cardiomyopathy and tibial muscular dystrophy.[34] Further research also suggests that no genetically linked form of any dystrophy or myopathy can be safely excluded from being caused by a mutation on the TTN gene.[35] Truncating mutations in dilated cardiomyopathy patients are most commonly found in the A region; although truncations in the upstream I region might be expected to prevent translation of the A region entirely, alternative splicing creates some transcripts that do not encounter the premature stop codon, ameliorating its effect.[36] Autoantibodies to titin are produced in patients with the autoimmune disease scleroderma.[31] # Interactions Titin has been shown to interact with: - ANK1,[37] - ANKRD1,[38] - ANKRD23[38] - CAPN3,[39][40] - FHL2,[41] - OBSCN,[42] - TCAP,[43][44][45][46] and - TRIM63.[47] # Linguistic significance The name titin is derived from the Greek Titan (a giant deity, anything of great size).[13] As the largest known protein, titin also has the longest IUPAC name of a protein. The full chemical name of the human canonical form of titin, which starts methionyl... and ends ...isoleucine, contains 189,819 letters and is sometimes stated to be the longest word in the English language, or of any language.[48] However, lexicographers regard generic names of chemical compounds as verbal formulae rather than English words.[49] The full word can be found here on Wiktionary.	https://www.wikidoc.org/index.php/Titin
d5ed5d38ccac5392b29425f149d987ffcd412fa9	wikidoc	Tooth	Tooth # Overview Teeth (singular, tooth) are structures found in the jaws of many vertebrates that are used to tear, scrape, and chew food. Some animals, particularly carnivores, also use teeth for hunting or defense. The roots of teeth are covered by gums. Teeth are among the most distinctive (and long-lasting) features of mammal species. Paleontologists use teeth to identify fossil species and determine their relationships. The shape of an animal's teeth is related to its diet. For example, plant matter is hard to digest, so herbivores have many molars for chewing. Carnivores, on the other hand, need canines to kill and tear meat. Humans are diphyodont, meaning that they develop two sets of teeth. The first set (the "baby," "milk," "primary" or "deciduous" set) normally starts to appear at about six months of age, although some babies are born with one or more visible teeth, known as neonatal teeth. Normal tooth eruption at about six months is known as teething and can be quite painful for an infant. Some animals develop only one set of teeth (monophyodont) while others develop many sets (polyphyodont). Sharks, for example, grow a new set of teeth every two weeks to replace worn teeth. Rodent incisors grow and wear away continually through gnawing, maintaining relatively constant length. Some rodent species, such as the sibling vole and the guinea pig, have continuously growing molars in addition to incisors. # Anatomy Dental anatomy is a field of anatomy dedicated to the study of tooth structures. The development, appearance, and classification of teeth fall within its purview, though dental occlusion, or contact among teeth, does not. Dental anatomy is also a taxonomical science as it is concerned with the naming of teeth and their structures. This information serves a practical purpose for dentists, enabling them to easily identify teeth and structures during treatment. The anatomic crown of a tooth is the area covered in enamel above the cementoenamel junction (CEJ). The majority of the crown is composed of dentin with the pulp chamber in the center. The crown is within bone before eruption. After eruption, it is almost always visible. The anatomic root is found below the cementoenamel junction and is covered with cementum. As with the crown, dentin composes most of the root, which normally have pulp canals. A tooth may have multiple roots or just one root. Canines and most premolars, except for maxillary (upper) first premolars, usually have one root. Maxillary first premolars and mandibular molars usually have two roots. Maxillary molars usually have three roots. Additional roots are referred to as supernumerary roots. Humans usually have 20 primary teeth (also called deciduous, baby, or milk teeth) and 32 permanent teeth. Among primary teeth, 10 are found in the maxilla and the other 10 in the mandible. Teeth are classified as incisors, canines, and molars. In the primary set of teeth, there are two types of incisors, centrals and laterals, and two types of molars, first and second. All primary teeth are replaced with permanent counterparts except for molars, which are replaced by permanent premolars. Among permanent teeth, 16 are found in the maxilla with the other 16 in the mandible. The maxillary teeth are the maxillary central incisor, maxillary lateral incisor, maxillary canine, maxillary first premolar, maxillary second premolar, maxillary first molar, maxillary second molar, and maxillary third molar. The mandibular teeth are the mandibular central incisor, mandibular lateral incisor, mandibular canine, mandibular first premolar, mandibular second premolar, mandibular first molar, mandibular second molar, and mandibular third molar. Third molars are commonly called "wisdom teeth" and may never erupt into the mouth or form at all. If any additional teeth form, for example, fourth and fifth molars, which are rare, they are referred to as supernumerary teeth. Most teeth have identifiable features that distinguish them from others. There are several different notation systems to refer to a specific tooth. The three most commons systems are the FDI World Dental Federation notation, the universal numbering system, and Palmer notation method. The FDI system is used worldwide, and the universal is used widely in the United States. # Parts ## Enamel Enamel is the hardest and most highly mineralized substance of the body and is one of the four major tissues which make up the tooth, along with dentin, cementum, and dental pulp. It is normally visible and must be supported by underlying dentin. Ninety-six percent of enamel consists of mineral, with water and organic material composing the rest. The normal color of enamel varies from light yellow to grayish white. At the edges of teeth where there is no dentin underlying the enamel, the color sometimes has a slightly blue tone. Since enamel is semitranslucent, the color of dentin and any restorative dental material underneath the enamel strongly affects the appearance of a tooth. Enamel varies in thickness over the surface of the tooth and is often thickest at the cusp, up to 2.5 mm, and thinnest at its border, which is seen clinically as the cementoenamel junction (CEJ). Enamel's primary mineral is hydroxyapatite, which is a crystalline calcium phosphate. The large amount of minerals in enamel accounts not only for its strength but also for its brittleness. Dentin, which is less mineralized and less brittle, compensates for enamel and is necessary as a support. Unlike dentin and bone, enamel does not contain collagen. Instead, it has two unique classes of proteins called amelogenins and enamelins. While the role of these proteins is not fully understood, it is believed that they aid in the development of enamel by serving as framework support among other functions. ## Dentin Dentin is the substance between enamel or cementum and the pulp chamber. It is secreted by the odontoblasts of the dental pulp. The formation of dentin is known as dentinogenesis. The porous, yellow-hued material is made up of 70% inorganic materials, 20% organic materials, and 10% water by weight. Because it is softer than enamel, it decays more rapidly and is subject to severe cavities if not properly treated, but dentin still acts as a protective layer and supports the crown of the tooth. Dentin is a mineralized connective tissue with an organic matrix of collagenous proteins. Dentin has microscopic channels, called dentinal tubules, which radiate outward through the dentin from the pulp cavity to the exterior cementum or enamel border. The diameter of these tubules range from 2.5 μm near the pulp, to 1.2 μm in the midportion, and 900 nm near the dentino-enamel junction. Although they may have tiny side-branches, the tubules do not intersect with each other. Their length is dictated by the radius of the tooth. The three dimensional configuration of the dentinal tubules is genetically determined. ## Cementum Cementum is a specialized bony substance covering the root of a tooth. It is approximately 45% inorganic material (mainly hydroxyapatite), 33% organic material (mainly collagen) and 22% water. Cementum is excreted by cementoblasts within the root of the tooth and is thickest at the root apex. Its coloration is yellowish and it is softer than either dentin or enamel. The principle role of cementum is to serve as a medium by which the periodontal ligaments can attach to the tooth for stability. At the cementoenamel junction, the cementum is acellular due to its lack of cellular components, and this acellular type covers at least ⅔ of the root. The more permeable form of cementum, cellular cementum, covers about ⅓ of the root apex. ## Pulp The dental pulp is the central part of the tooth filled with soft connective tissue. This tissue contains blood vessels and nerves that enter the tooth from a hole at the apex of the root. Along the border between the dentin and the pulp are odontoblasts, which initiate the formation of dentin. Other cells in the pulp include fibroblasts, preodontoblasts, macrophages and T lymphocytes. The pulp is commonly called "the nerve" of the tooth. # Development Tooth development is the complex process by which teeth form from embryonic cells, grow, and erupt into the mouth. Although many diverse species have teeth, non-human tooth development is largely the same as in humans. For human teeth to have a healthy oral environment, enamel, dentin, cementum, and the periodontium must all develop during appropriate stages of fetal development. Primary (baby) teeth start to form between the sixth and eighth weeks in utero, and permanent teeth begin to form in the twentieth week in utero. If teeth do not start to develop at or near these times, they will not develop at all. A significant amount of research has focused on determining the processes that initiate tooth development. It is widely accepted that there is a factor within the tissues of the first branchial arch that is necessary for the development of teeth. Tooth development is commonly divided into the following stages: the bud stage, the cap, the bell, and finally maturation. The staging of tooth development is an attempt to categorize changes that take place along a continuum; frequently it is difficult to decide what stage should be assigned to a particular developing tooth. This determination is further complicated by the varying appearance of different histologic sections of the same developing tooth, which can appear to be different stages. The tooth bud (sometimes called the tooth germ) is an aggregation of cells that eventually forms a tooth. It is organized into three parts: the enamel organ, the dental papilla and the dental follicle. The enamel organ is composed of the outer enamel epithelium, inner enamel epithelium, stellate reticulum and stratum intermedium. These cells give rise to ameloblasts, which produce enamel and the reduced enamel epithelium. The growth of cervical loop cells into the deeper tissues forms Hertwig's Epithelial Root Sheath, which determines a tooth's root shape. The dental papilla contains cells that develop into odontoblasts, which are dentin-forming cells. Additionally, the junction between the dental papilla and inner enamel epithelium determines the crown shape of a tooth. The dental follicle gives rise to three important entities: cementoblasts, osteoblasts, and fibroblasts. Cementoblasts form the cementum of a tooth. Osteoblasts give rise to the alveolar bone around the roots of teeth. Fibroblasts develop the periodontal ligaments which connect teeth to the alveolar bone through cementum. # Eruption Tooth eruption in humans is a process in tooth development in which the teeth enter the mouth and become visible. Current research indicates that the periodontal ligaments play an important role in tooth eruption. Primary teeth erupt into the mouth from around six months until two years of age. These teeth are the only ones in the mouth until a person is about six years old. At that time, the first permanent tooth erupts. This stage, during which a person has a combination of primary and permanent teeth, is known as the mixed stage. The mixed stage lasts until the last primary tooth is lost and the remaining permanent teeth erupt into the mouth. There have been many theories about the cause of tooth eruption. One theory proposes that the developing root of a tooth pushes it into the mouth. Another, known as the cushioned hammock theory, resulted from microscopic study of teeth, which was thought to show a ligament around the root. It was later discovered that the "ligament" was merely an artifact created in the process of preparing the slide. Currently, the most widely held belief is that the periodontal ligaments provide the main impetus for the process. # Supporting structures The periodontium is the supporting structure of a tooth, helping to attach the tooth to surrounding tissues and to allow sensations of touch and pressure. It consists of the cementum, periodontal ligaments, alveolar bone, and gingiva. Of these, cementum is the only one that is a part of a tooth. Periodontal ligaments connect the alveolar bone to the cementum. Alveolar bone surrounds the roots of teeth to provide support and creates what is commonly called an alveolus, or "socket". Lying over the bone is the gingiva, which is readily visible in the mouth. ## Periodontal ligaments The periodontal ligament is a specialized connective tissue that attaches the cementum of a tooth to the alveolar bone. This tissue covers the root of the tooth within the bone. Each ligament has a width of 0.15 - 0.38 mm, but this size decreases over time. The functions of the periodontal ligaments include attachment of the tooth to the bone, support for the tooth, formation and resorption of bone during tooth movement, sensation, and eruption. The cells of the periodontal ligaments include osteoblasts, osteoclasts, fibroblasts, macrophages, cementoblasts, and epithelial cell rests of Malassez. Consisting of mostly Type I and III collagen, the fibers are grouped in bundles and named according to their location. The groups of fibers are named alveolar crest, horizontal, oblique, periapical, and interradicular fibers. The nerve supply generally enters from the bone apical to the tooth and forms a network around the tooth toward the crest of the gingiva. When pressure is exerted on a tooth, such as during chewing or biting, the tooth moves slightly in its socket and stretches the periodontal ligaments. The nerve fibers can then send the information to the central nervous system for interpretation. ## Alveolar bone The alveolar bone is the bone of the jaw which forms the alveolus around teeth. Like any other bone in the human body, alveolar bone is modified throughout life. Osteoblasts create bone and osteoclasts destroy it, especially if force is placed on a tooth. As is the case when movement of teeth is attempted through orthodontics, an area of bone under compressive force from a tooth moving toward it has a high osteoclast level, resulting in bone resorption. An area of bone receiving tension from periodontal ligaments attached to a tooth moving away from it has a high number of osteoblasts, resulting in bone formation. ## Gingiva The gingiva ("gums") is the mucosal tissue that overlays the jaws. There are three different types of epithelium associated with the gingiva: gingival, junctional, and sulcular epithelium. These three types form from a mass of epithelial cells known as the epithelial cuff between the tooth and the mouth. The gingival epithelium is not associated directly with tooth attachment and is visible in the mouth. The junctional epithelium, composed of the basal lamina and hemidesmosomes, forms an attachment to the tooth. The sulcular epithelium is nonkeratinized stratified squamous tissue on the gingiva which touches but is not attached to the tooth. This leaves a small potential space between the gingiva and tooth which can collect bacteria, plaque, and calculus. # Tooth decay ## Plaque Plaque is a biofilm consisting of large quantities of various bacteria that form on teeth. If not removed regularly, plaque buildup can lead to dental cavities (caries) or periodontal problems such as gingivitis. Given time, plaque can mineralize along the gingiva, forming tartar. The microorganisms that form the biofilm are almost entirely bacteria (mainly streptococcus and anaerobes), with the composition varying by location in the mouth. Streptococcus mutans is the most important bacteria associated with dental caries. Certain bacteria in the mouth live off the remains of foods, especially sugars and starches. In the absence of oxygen they produce lactic acid, which dissolves the calcium and phosphorus in the enamel. This process, known as "demineralisation", leads to tooth destruction. Saliva gradually neutralises the acids which cause the pH of the tooth surface to rise above the critical pH. This causes 'remineralisation', the return of the dissolved minerals to the enamel. If there is sufficient time between the intake of foods then the impact is limited and the teeth can repair themselves. Saliva is unable to penetrate through plaque, however, to neutralize the acid produced by the bacteria. ## Caries (Cavities) Dental caries, also described as "tooth decay" or "dental cavities", is an infectious disease which damages the structures of teeth. The disease can lead to pain, tooth loss, infection, and, in severe cases, death. Dental caries has a long history, with evidence showing the disease was present in the Bronze, Iron, and Middle ages but also prior to the neolithic period. The largest increases in the prevalence of caries have been associated with diet changes. Today, caries remains one of the most common diseases throughout the world. In the United States, dental caries is the most common chronic childhood disease, being at least five times more common than asthma. Countries that have experienced an overall decrease in cases of tooth decay continue to have a disparity in the distribution of the disease. Among children in the United States and Europe, 60-80% of cases of dental caries occur in 20% of the population. Tooth decay is caused by certain types of acid-producing bacteria which cause the most damage in the presence of fermentable carbohydrates such as sucrose, fructose, and glucose. The resulting acidic levels in the mouth affect teeth because a tooth's special mineral content causes it to be sensitive to low pH. Depending on the extent of tooth destruction, various treatments can be used to restore teeth to proper form, function, and aesthetics, but there is no known method to regenerate large amounts of tooth structure. Instead, dental health organizations advocate preventative and prophylactic measures, such as regular oral hygiene and dietary modifications, to avoid dental caries. # Tooth care Oral hygiene is the practice of keeping the mouth clean and is a means of preventing dental caries, gingivitis, periodontal disease, bad breath, and other dental disorders. It consists of both professional and personal care. Regular cleanings, usually done by dentists and dental hygienists, remove tartar (mineralized plaque) that may develop even with careful brushing and flossing. Professional cleaning includes tooth scaling, using various instruments or devices to loosen and remove deposits from teeth. The purpose of cleaning teeth is to remove plaque, which consists mostly of bacteria. Healthcare professionals recommend regular brushing twice a day (in the morning and in the evening, or after meals) in order to prevent formation of plaque and tartar. A toothbrush is able to remove most plaque, excepting areas between teeth. As a result, flossing is also considered a necessity to maintain oral hygiene. When used correctly, dental floss removes plaque from between teeth and at the gum line, where periodontal disease often begins and could develop caries. Electric toothbrushes are not considered more effective than manual brushes for most people. The most important advantage of electric toothbrushes is their ability to aid people with dexterity difficulties, such as those associated with rheumatoid arthritis. In addition, fluoride therapy is often recommended to protect against dental caries. Water fluoridation and fluoride supplements decrease the incidence of dental caries. Fluoride helps prevent dental decay by binding to the hydroxyapatite crystals in enamel. The incorporated fluoride makes enamel more resistant to demineralization and thus more resistant to decay. Topical fluoride, such as a fluoride toothpaste or mouthwash, is also recommended to protect teeth surfaces. Many dentists include application of topical fluoride solutions as part of routine cleanings. # Restorations After a tooth has been damaged or destroyed, restoration of the missing structure can be achieved with a variety of treatments. Restorations may be created from a variety of materials, including amalgam, gold, porcelain, and composite. Small restorations placed inside a tooth are referred to as "intracoronal restorations". These restorations may be formed directly in the mouth or may be cast using the lost-wax technique, such as for some inlays and onlays. When larger portions of a tooth are lost, an "extracoronal restoration" may be fabricated, such as a crown or a veneer, to restore the involved tooth. When a tooth is lost, dentures, bridges, or implants may be used as replacements. Dentures are usually the least costly whereas implants are usually the most expensive. Dentures may replace complete arches of the mouth or only a partial number of teeth. Bridges replace smaller spaces of missing teeth and use adjacent teeth to support the restoration. Dental implants may be used to replace a single tooth or a series of teeth. Though implants are the most expensive treatment option, they are often the most desirable restoration because of their esthetics and function. To improve the function of dentures, implants may be used as support. # Abnormalities Tooth abnormalities may be categorized according to whether they have environmental or developmental causes. While environmental abnormalities may appear to have an obvious cause, there may not appear to be any known cause for some developmental abnormalities. Environmental forces may affect teeth during development, destroy tooth structure after development, discolor teeth at any stage of development, or alter the course of tooth eruption. Developmental abnormalities most commonly affect the number, size, shape, and structure of teeth. ## Environmental ### Alteration during tooth development Tooth abnormalities caused by environmental factors during tooth development have long-lasting effects. Enamel and dentin do not regenerate after they mineralize initially. Enamel hypoplasia is a condition in which the amount of enamel formed is inadequate. This results either in pits and grooves in areas of the tooth or in widespread absence of enamel. Diffuse opacities of enamel does not affect the amount of enamel but changes its appearance. Affected enamel has a different translucency than the rest of the tooth. Demarcated opacities of enamel have sharp boundaries where the translucency decreases and manifest a white, cream, yellow, or brown color. All these may be caused by a systemic event, such as an exanthematous fever. Turner's hypoplasia is a portion of missing or diminished enamel on a permanent tooth usually from a prior infection of a nearby primary tooth. Hypoplasia may also result from antineoplastic therapy. Dental fluorosis is condition which results from ingesting excessive amounts of fluoride and leads to teeth which are spotted, yellow, brown, black or sometimes pitted. Enamel hypoplasia resulting from syphilis is frequently referred to as Hutchinson's teeth, which is considered one part of Hutchinson's triad. ### Destruction after development Tooth destruction from processes other than dental caries is considered a normal physiologic process but may become severe enough to become a pathologic condition. Attrition is the loss of tooth structure by mechanical forces from opposing teeth. Attrition initially affects the enamel and, if unchecked, may proceed to the underlying dentin. Abrasion is the loss of tooth structure by mechanical forces from a foreign element. If this force begins at the cementoenamel junction, then progression of tooth loss can be rapid since enamel is very thin in this region of the tooth. A common source of this type of tooth wear is excessive force when using a toothbrush. Erosion is the loss of tooth structure due to chemical dissolution by acids not of bacterial origin. Signs of tooth destruction from erosion is a common characteristic in the mouths of people with bulimia since vomiting results in exposure of the teeth to gastric acids. Another important source of erosive acids are from frequent sucking of lemon juice. Abfraction is the loss of tooth structure from flexural forces. As teeth flex under pressure, the arrangement of teeth touching each other, known as occlusion, causes tension on one side of the tooth and compression on the other side of the tooth. This is believed to cause V-shaped depressions on the side under tension and C-shaped depressions on the side under compression. When tooth destruction occurs at the roots of teeth, the process is referred to as internal resorption, when caused by cells within the pulp, or external resorption, when caused by cells in the periodontal ligament. ### Discoloration Discoloration of teeth may result from bacteria stains, tobacco, tea, coffee, foods with an abundance of chlorophyll, restorative materials, and medications. Stains from bacteria may cause colors varying from green to black to orange. Green stains also result from foods with chlorophyll or excessive exposure to copper or nickel. Amalgam, a common dental restorative material, may turn adjacent areas of teeth black or gray. Chlorhexidine, a mouthwash, is associated with causing yellow-brown stains near the gingiva on teeth. Systemic disorders also can cause tooth discoloration. Congenital erythropoietic porphyria causes porphyrins to be deposited in teeth, causing a red-brown coloration. Blue discoloration may occur with alkaptonuria and rarely with Parkinson's disease. Erythroblastosis fetalis and biliary atresia are diseases which may cause teeth to appear green from the deposition of biliverdin. Also, trauma may change a tooth to a pink, yellow, or dark gray color. Pink and red discolorations are also associated in patients with lepromatous leprosy. Some medications, such as tetracycline antibiotics, may become incorporated into the structure of a tooth, causing intrinsic staining of the teeth. ### Alteration of eruption Tooth eruption may be altered by some environmental factors. When eruption is prematurely stopped, the tooth is said to be impacted. The most common cause of tooth impaction is lack of space in the mouth for the tooth. Other causes may be tumors, cysts, trauma, and thickened bone or soft tissue. Ankylosis of a tooth occurs when the tooth has already erupted into the mouth but the cementum or dentin has fused with the alveolar bone. This may cause a person to retain their primary tooth instead of having it replaced by a permanent one. A technique for altering the natural progression of eruption is employed by orthodontists who wish to delay or speed up the eruption of certain teeth for reasons of space maintenance or otherwise preventing crowding and/or spacing. If a primary tooth is extracted prior to the root of its succeeding permanent tooth reaching ⅓ of its total growth, the eruption of the permanent tooth will be delayed. Conversely, if the roots of the permanent tooth are more than ⅔ complete, the eruption of the permanent tooth will be accelerated. Between ⅓ and ⅔, it is unknown exactly what will occur to the speed of eruption. ## Developmental ### Abnormality in number Anodontia is the total lack of tooth development. Hyperdontia is the presence of a higher-than-normal number of teeth, where as Hypodontia is the lack of some teeth. Usually, hypodontia refers to the lack of development of one or more teeth, and oligodontia may be used to describe the absence of 6 or more teeth. Some systemic disorders which may result in hyperdontia include Apert syndrome, Cleidocranial dysostosis, Crouzon syndrome, Ehlers-Danlos syndrome, Gardner syndrome, and Sturge-Weber syndrome. Some systemic disorders which may result in hypodontia include Crouzon syndrome, Ectodermal dysplasia, Ehlers-Danlos syndrome, and Gorlin syndrome. ### Abnormality in size Microdontia is a condition where teeth are smaller than the usual size, and macrodontia is where teeth are larger than the usual size. Microdontia of a single tooth is more likely to occur in a maxillary lateral incisor. The second most likely tooth to have microdontia are third molars. Macrodontia of all the teeth is known to occur in pituitary gigantism and pineal hyperplasia. It may also occur on one side of the face in cases of hemifacial hyperplasia. ### Abnormality in shape Gemination occurs when a developing tooth incompletely splits into the formation of two teeth. Fusion is the union of two adjacent teeth during development. Concrescence is the fusion of two separate teeth only in their cementum. Accessory cusps are additional cusps on a tooth and may manifest as a Talon cusp, Cusp of Carabelli, or Dens evaginatus. Dens invaginatus, also called Dens in dente, is a deep invagination in a tooth causing the appearance of a tooth within a tooth. Ectopic enamel is enamel found in an unusual location, such as the root of a tooth. Taurodontism is a condition where the body of the tooth and pulp chamber is enlarged, and is associated with Klinefelter syndrome, Tricho-dento-osseous syndrome, Triple X syndrome, and XYY syndrome. Hypercementosis is excessive formation of cementum, which may result from trauma, inflammation, acromegaly, rheumatic fever, and Paget's disease of bone. A dilaceration is a bend in the root which may have been caused by trauma to the tooth during formation. Supernumerary roots is the presence of a greater number of roots on a tooth than expected. ### Abnormality in structure Amelogenesis imperfecta is a condition in which enamel does not form properly or at all. Dentinogenesis imperfecta is a condition in which dentin does not form properly and is sometimes associated with osteogenesis imperfecta. Dentin dysplasia is a disorder in which the roots and pulp of teeth may be affected. Regional odontodysplasia is a disorder affecting enamel, dentin, and pulp and causes the teeth to appear "ghostly" on radiographs. # In animals Teeth vary greatly among animals. Some animals, such as turtles and tortoises, are toothless. Others, such as sharks, may go through many teeth in their lifetime. Walrus tusks are canine teeth that grow continuously throughout life. Dog teeth are less likely than human teeth to form dental caries because of the very high pH of dog saliva, which prevents enamel from demineralizing. Unlike humans whose ameloblasts die after tooth development, rodents continually produce enamel and must wear down their teeth by gnawing on various materials. Horse teeth include twelve premolars, twelve molars, and twelve incisors. The structure of horse teeth is different from human teeth as the enamel and dentin layers are intertwined.	Tooth Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] # Overview Template:Infobox Anatomy Teeth (singular, tooth) are structures found in the jaws of many vertebrates that are used to tear, scrape, and chew food. Some animals, particularly carnivores, also use teeth for hunting or defense. The roots of teeth are covered by gums. Teeth are among the most distinctive (and long-lasting) features of mammal species. Paleontologists use teeth to identify fossil species and determine their relationships. The shape of an animal's teeth is related to its diet. For example, plant matter is hard to digest, so herbivores have many molars for chewing. Carnivores, on the other hand, need canines to kill and tear meat. Humans are diphyodont, meaning that they develop two sets of teeth. The first set (the "baby," "milk," "primary" or "deciduous" set) normally starts to appear at about six months of age, although some babies are born with one or more visible teeth, known as neonatal teeth. Normal tooth eruption at about six months is known as teething and can be quite painful for an infant. Some animals develop only one set of teeth (monophyodont) while others develop many sets (polyphyodont). Sharks, for example, grow a new set of teeth every two weeks to replace worn teeth. Rodent incisors grow and wear away continually through gnawing, maintaining relatively constant length. Some rodent species, such as the sibling vole and the guinea pig, have continuously growing molars in addition to incisors.[1][2] # Anatomy Dental anatomy is a field of anatomy dedicated to the study of tooth structures. The development, appearance, and classification of teeth fall within its purview, though dental occlusion, or contact among teeth, does not. Dental anatomy is also a taxonomical science as it is concerned with the naming of teeth and their structures. This information serves a practical purpose for dentists, enabling them to easily identify teeth and structures during treatment. The anatomic crown of a tooth is the area covered in enamel above the cementoenamel junction (CEJ).[3] The majority of the crown is composed of dentin with the pulp chamber in the center.[4] The crown is within bone before eruption.[5] After eruption, it is almost always visible. The anatomic root is found below the cementoenamel junction and is covered with cementum. As with the crown, dentin composes most of the root, which normally have pulp canals. A tooth may have multiple roots or just one root. Canines and most premolars, except for maxillary (upper) first premolars, usually have one root. Maxillary first premolars and mandibular molars usually have two roots. Maxillary molars usually have three roots. Additional roots are referred to as supernumerary roots. Humans usually have 20 primary teeth (also called deciduous, baby, or milk teeth) and 32 permanent teeth. Among primary teeth, 10 are found in the maxilla and the other 10 in the mandible. Teeth are classified as incisors, canines, and molars. In the primary set of teeth, there are two types of incisors, centrals and laterals, and two types of molars, first and second. All primary teeth are replaced with permanent counterparts except for molars, which are replaced by permanent premolars. Among permanent teeth, 16 are found in the maxilla with the other 16 in the mandible. The maxillary teeth are the maxillary central incisor, maxillary lateral incisor, maxillary canine, maxillary first premolar, maxillary second premolar, maxillary first molar, maxillary second molar, and maxillary third molar. The mandibular teeth are the mandibular central incisor, mandibular lateral incisor, mandibular canine, mandibular first premolar, mandibular second premolar, mandibular first molar, mandibular second molar, and mandibular third molar. Third molars are commonly called "wisdom teeth" and may never erupt into the mouth or form at all. If any additional teeth form, for example, fourth and fifth molars, which are rare, they are referred to as supernumerary teeth.[6] Most teeth have identifiable features that distinguish them from others. There are several different notation systems to refer to a specific tooth. The three most commons systems are the FDI World Dental Federation notation, the universal numbering system, and Palmer notation method. The FDI system is used worldwide, and the universal is used widely in the United States. # Parts ## Enamel Enamel is the hardest and most highly mineralized substance of the body and is one of the four major tissues which make up the tooth, along with dentin, cementum, and dental pulp.[7] It is normally visible and must be supported by underlying dentin. Ninety-six percent of enamel consists of mineral, with water and organic material composing the rest.[8] The normal color of enamel varies from light yellow to grayish white. At the edges of teeth where there is no dentin underlying the enamel, the color sometimes has a slightly blue tone. Since enamel is semitranslucent, the color of dentin and any restorative dental material underneath the enamel strongly affects the appearance of a tooth. Enamel varies in thickness over the surface of the tooth and is often thickest at the cusp, up to 2.5 mm, and thinnest at its border, which is seen clinically as the cementoenamel junction (CEJ).[9] Enamel's primary mineral is hydroxyapatite, which is a crystalline calcium phosphate.[10] The large amount of minerals in enamel accounts not only for its strength but also for its brittleness.[11] Dentin, which is less mineralized and less brittle, compensates for enamel and is necessary as a support.[10] Unlike dentin and bone, enamel does not contain collagen. Instead, it has two unique classes of proteins called amelogenins and enamelins. While the role of these proteins is not fully understood, it is believed that they aid in the development of enamel by serving as framework support among other functions.[12] ## Dentin Dentin is the substance between enamel or cementum and the pulp chamber. It is secreted by the odontoblasts of the dental pulp.[13] The formation of dentin is known as dentinogenesis. The porous, yellow-hued material is made up of 70% inorganic materials, 20% organic materials, and 10% water by weight.[14] Because it is softer than enamel, it decays more rapidly and is subject to severe cavities if not properly treated, but dentin still acts as a protective layer and supports the crown of the tooth. Dentin is a mineralized connective tissue with an organic matrix of collagenous proteins. Dentin has microscopic channels, called dentinal tubules, which radiate outward through the dentin from the pulp cavity to the exterior cementum or enamel border.[15] The diameter of these tubules range from 2.5 μm near the pulp, to 1.2 μm in the midportion, and 900 nm near the dentino-enamel junction.[16] Although they may have tiny side-branches, the tubules do not intersect with each other. Their length is dictated by the radius of the tooth. The three dimensional configuration of the dentinal tubules is genetically determined. ## Cementum Cementum is a specialized bony substance covering the root of a tooth.[13] It is approximately 45% inorganic material (mainly hydroxyapatite), 33% organic material (mainly collagen) and 22% water. Cementum is excreted by cementoblasts within the root of the tooth and is thickest at the root apex. Its coloration is yellowish and it is softer than either dentin or enamel. The principle role of cementum is to serve as a medium by which the periodontal ligaments can attach to the tooth for stability. At the cementoenamel junction, the cementum is acellular due to its lack of cellular components, and this acellular type covers at least ⅔ of the root.[17] The more permeable form of cementum, cellular cementum, covers about ⅓ of the root apex.[18] ## Pulp The dental pulp is the central part of the tooth filled with soft connective tissue.[14] This tissue contains blood vessels and nerves that enter the tooth from a hole at the apex of the root.[19] Along the border between the dentin and the pulp are odontoblasts, which initiate the formation of dentin.[14] Other cells in the pulp include fibroblasts, preodontoblasts, macrophages and T lymphocytes.[20] The pulp is commonly called "the nerve" of the tooth. # Development Tooth development is the complex process by which teeth form from embryonic cells, grow, and erupt into the mouth. Although many diverse species have teeth, non-human tooth development is largely the same as in humans. For human teeth to have a healthy oral environment, enamel, dentin, cementum, and the periodontium must all develop during appropriate stages of fetal development. Primary (baby) teeth start to form between the sixth and eighth weeks in utero, and permanent teeth begin to form in the twentieth week in utero.[21] If teeth do not start to develop at or near these times, they will not develop at all. A significant amount of research has focused on determining the processes that initiate tooth development. It is widely accepted that there is a factor within the tissues of the first branchial arch that is necessary for the development of teeth.[22] Tooth development is commonly divided into the following stages: the bud stage, the cap, the bell, and finally maturation. The staging of tooth development is an attempt to categorize changes that take place along a continuum; frequently it is difficult to decide what stage should be assigned to a particular developing tooth.[22] This determination is further complicated by the varying appearance of different histologic sections of the same developing tooth, which can appear to be different stages. The tooth bud (sometimes called the tooth germ) is an aggregation of cells that eventually forms a tooth. It is organized into three parts: the enamel organ, the dental papilla and the dental follicle.[23] The enamel organ is composed of the outer enamel epithelium, inner enamel epithelium, stellate reticulum and stratum intermedium.[23] These cells give rise to ameloblasts, which produce enamel and the reduced enamel epithelium. The growth of cervical loop cells into the deeper tissues forms Hertwig's Epithelial Root Sheath, which determines a tooth's root shape. The dental papilla contains cells that develop into odontoblasts, which are dentin-forming cells.[23] Additionally, the junction between the dental papilla and inner enamel epithelium determines the crown shape of a tooth.[24] The dental follicle gives rise to three important entities: cementoblasts, osteoblasts, and fibroblasts. Cementoblasts form the cementum of a tooth. Osteoblasts give rise to the alveolar bone around the roots of teeth. Fibroblasts develop the periodontal ligaments which connect teeth to the alveolar bone through cementum.[25] # Eruption Tooth eruption in humans is a process in tooth development in which the teeth enter the mouth and become visible. Current research indicates that the periodontal ligaments play an important role in tooth eruption. Primary teeth erupt into the mouth from around six months until two years of age. These teeth are the only ones in the mouth until a person is about six years old. At that time, the first permanent tooth erupts. This stage, during which a person has a combination of primary and permanent teeth, is known as the mixed stage. The mixed stage lasts until the last primary tooth is lost and the remaining permanent teeth erupt into the mouth. There have been many theories about the cause of tooth eruption. One theory proposes that the developing root of a tooth pushes it into the mouth.[26] Another, known as the cushioned hammock theory, resulted from microscopic study of teeth, which was thought to show a ligament around the root. It was later discovered that the "ligament" was merely an artifact created in the process of preparing the slide.[27] Currently, the most widely held belief is that the periodontal ligaments provide the main impetus for the process.[28] # Supporting structures The periodontium is the supporting structure of a tooth, helping to attach the tooth to surrounding tissues and to allow sensations of touch and pressure.[29] It consists of the cementum, periodontal ligaments, alveolar bone, and gingiva. Of these, cementum is the only one that is a part of a tooth. Periodontal ligaments connect the alveolar bone to the cementum. Alveolar bone surrounds the roots of teeth to provide support and creates what is commonly called an alveolus, or "socket". Lying over the bone is the gingiva, which is readily visible in the mouth. ## Periodontal ligaments The periodontal ligament is a specialized connective tissue that attaches the cementum of a tooth to the alveolar bone. This tissue covers the root of the tooth within the bone. Each ligament has a width of 0.15 - 0.38 mm, but this size decreases over time.[30] The functions of the periodontal ligaments include attachment of the tooth to the bone, support for the tooth, formation and resorption of bone during tooth movement, sensation, and eruption.[31] The cells of the periodontal ligaments include osteoblasts, osteoclasts, fibroblasts, macrophages, cementoblasts, and epithelial cell rests of Malassez.[32] Consisting of mostly Type I and III collagen, the fibers are grouped in bundles and named according to their location. The groups of fibers are named alveolar crest, horizontal, oblique, periapical, and interradicular fibers.[33] The nerve supply generally enters from the bone apical to the tooth and forms a network around the tooth toward the crest of the gingiva.[34] When pressure is exerted on a tooth, such as during chewing or biting, the tooth moves slightly in its socket and stretches the periodontal ligaments. The nerve fibers can then send the information to the central nervous system for interpretation. ## Alveolar bone The alveolar bone is the bone of the jaw which forms the alveolus around teeth.[35] Like any other bone in the human body, alveolar bone is modified throughout life. Osteoblasts create bone and osteoclasts destroy it, especially if force is placed on a tooth.[29] As is the case when movement of teeth is attempted through orthodontics, an area of bone under compressive force from a tooth moving toward it has a high osteoclast level, resulting in bone resorption. An area of bone receiving tension from periodontal ligaments attached to a tooth moving away from it has a high number of osteoblasts, resulting in bone formation. ## Gingiva The gingiva ("gums") is the mucosal tissue that overlays the jaws. There are three different types of epithelium associated with the gingiva: gingival, junctional, and sulcular epithelium. These three types form from a mass of epithelial cells known as the epithelial cuff between the tooth and the mouth.[36] The gingival epithelium is not associated directly with tooth attachment and is visible in the mouth. The junctional epithelium, composed of the basal lamina and hemidesmosomes, forms an attachment to the tooth.[31] The sulcular epithelium is nonkeratinized stratified squamous tissue on the gingiva which touches but is not attached to the tooth.[37] This leaves a small potential space between the gingiva and tooth which can collect bacteria, plaque, and calculus. # Tooth decay ## Plaque Plaque is a biofilm consisting of large quantities of various bacteria that form on teeth.[38] If not removed regularly, plaque buildup can lead to dental cavities (caries) or periodontal problems such as gingivitis. Given time, plaque can mineralize along the gingiva, forming tartar. The microorganisms that form the biofilm are almost entirely bacteria (mainly streptococcus and anaerobes), with the composition varying by location in the mouth.[39] Streptococcus mutans is the most important bacteria associated with dental caries. Certain bacteria in the mouth live off the remains of foods, especially sugars and starches. In the absence of oxygen they produce lactic acid, which dissolves the calcium and phosphorus in the enamel.[13] [40] This process, known as "demineralisation", leads to tooth destruction. Saliva gradually neutralises the acids which cause the pH of the tooth surface to rise above the critical pH. This causes 'remineralisation', the return of the dissolved minerals to the enamel. If there is sufficient time between the intake of foods then the impact is limited and the teeth can repair themselves. Saliva is unable to penetrate through plaque, however, to neutralize the acid produced by the bacteria. ## Caries (Cavities) Dental caries, also described as "tooth decay" or "dental cavities", is an infectious disease which damages the structures of teeth.[41] The disease can lead to pain, tooth loss, infection, and, in severe cases, death. Dental caries has a long history, with evidence showing the disease was present in the Bronze, Iron, and Middle ages but also prior to the neolithic period.[42] The largest increases in the prevalence of caries have been associated with diet changes.[42][43] Today, caries remains one of the most common diseases throughout the world. In the United States, dental caries is the most common chronic childhood disease, being at least five times more common than asthma.[44] Countries that have experienced an overall decrease in cases of tooth decay continue to have a disparity in the distribution of the disease.[45] Among children in the United States and Europe, 60-80% of cases of dental caries occur in 20% of the population.[46] Tooth decay is caused by certain types of acid-producing bacteria which cause the most damage in the presence of fermentable carbohydrates such as sucrose, fructose, and glucose.[47][48] The resulting acidic levels in the mouth affect teeth because a tooth's special mineral content causes it to be sensitive to low pH. Depending on the extent of tooth destruction, various treatments can be used to restore teeth to proper form, function, and aesthetics, but there is no known method to regenerate large amounts of tooth structure. Instead, dental health organizations advocate preventative and prophylactic measures, such as regular oral hygiene and dietary modifications, to avoid dental caries.[49] # Tooth care Oral hygiene is the practice of keeping the mouth clean and is a means of preventing dental caries, gingivitis, periodontal disease, bad breath, and other dental disorders. It consists of both professional and personal care. Regular cleanings, usually done by dentists and dental hygienists, remove tartar (mineralized plaque) that may develop even with careful brushing and flossing. Professional cleaning includes tooth scaling, using various instruments or devices to loosen and remove deposits from teeth. The purpose of cleaning teeth is to remove plaque, which consists mostly of bacteria.[50] Healthcare professionals recommend regular brushing twice a day (in the morning and in the evening, or after meals) in order to prevent formation of plaque and tartar.[49] A toothbrush is able to remove most plaque, excepting areas between teeth. As a result, flossing is also considered a necessity to maintain oral hygiene. When used correctly, dental floss removes plaque from between teeth and at the gum line, where periodontal disease often begins and could develop caries. Electric toothbrushes are not considered more effective than manual brushes for most people.[51] The most important advantage of electric toothbrushes is their ability to aid people with dexterity difficulties, such as those associated with rheumatoid arthritis. In addition, fluoride therapy is often recommended to protect against dental caries. Water fluoridation and fluoride supplements decrease the incidence of dental caries. Fluoride helps prevent dental decay by binding to the hydroxyapatite crystals in enamel.[52] The incorporated fluoride makes enamel more resistant to demineralization and thus more resistant to decay.[53] Topical fluoride, such as a fluoride toothpaste or mouthwash, is also recommended to protect teeth surfaces. Many dentists include application of topical fluoride solutions as part of routine cleanings. # Restorations After a tooth has been damaged or destroyed, restoration of the missing structure can be achieved with a variety of treatments. Restorations may be created from a variety of materials, including amalgam, gold, porcelain, and composite.[54] Small restorations placed inside a tooth are referred to as "intracoronal restorations". These restorations may be formed directly in the mouth or may be cast using the lost-wax technique, such as for some inlays and onlays. When larger portions of a tooth are lost, an "extracoronal restoration" may be fabricated, such as a crown or a veneer, to restore the involved tooth. When a tooth is lost, dentures, bridges, or implants may be used as replacements.[55] Dentures are usually the least costly whereas implants are usually the most expensive. Dentures may replace complete arches of the mouth or only a partial number of teeth. Bridges replace smaller spaces of missing teeth and use adjacent teeth to support the restoration. Dental implants may be used to replace a single tooth or a series of teeth. Though implants are the most expensive treatment option, they are often the most desirable restoration because of their esthetics and function. To improve the function of dentures, implants may be used as support.[56] # Abnormalities Tooth abnormalities may be categorized according to whether they have environmental or developmental causes.[57] While environmental abnormalities may appear to have an obvious cause, there may not appear to be any known cause for some developmental abnormalities. Environmental forces may affect teeth during development, destroy tooth structure after development, discolor teeth at any stage of development, or alter the course of tooth eruption. Developmental abnormalities most commonly affect the number, size, shape, and structure of teeth. ## Environmental ### Alteration during tooth development Tooth abnormalities caused by environmental factors during tooth development have long-lasting effects. Enamel and dentin do not regenerate after they mineralize initially. Enamel hypoplasia is a condition in which the amount of enamel formed is inadequate.[58] This results either in pits and grooves in areas of the tooth or in widespread absence of enamel. Diffuse opacities of enamel does not affect the amount of enamel but changes its appearance. Affected enamel has a different translucency than the rest of the tooth. Demarcated opacities of enamel have sharp boundaries where the translucency decreases and manifest a white, cream, yellow, or brown color. All these may be caused by a systemic event, such as an exanthematous fever.[59] Turner's hypoplasia is a portion of missing or diminished enamel on a permanent tooth usually from a prior infection of a nearby primary tooth. Hypoplasia may also result from antineoplastic therapy. Dental fluorosis is condition which results from ingesting excessive amounts of fluoride and leads to teeth which are spotted, yellow, brown, black or sometimes pitted. Enamel hypoplasia resulting from syphilis is frequently referred to as Hutchinson's teeth, which is considered one part of Hutchinson's triad.[60] ### Destruction after development Tooth destruction from processes other than dental caries is considered a normal physiologic process but may become severe enough to become a pathologic condition. Attrition is the loss of tooth structure by mechanical forces from opposing teeth.[61] Attrition initially affects the enamel and, if unchecked, may proceed to the underlying dentin. Abrasion is the loss of tooth structure by mechanical forces from a foreign element.[62] If this force begins at the cementoenamel junction, then progression of tooth loss can be rapid since enamel is very thin in this region of the tooth. A common source of this type of tooth wear is excessive force when using a toothbrush. Erosion is the loss of tooth structure due to chemical dissolution by acids not of bacterial origin.[63][64] Signs of tooth destruction from erosion is a common characteristic in the mouths of people with bulimia since vomiting results in exposure of the teeth to gastric acids. Another important source of erosive acids are from frequent sucking of lemon juice. Abfraction is the loss of tooth structure from flexural forces. As teeth flex under pressure, the arrangement of teeth touching each other, known as occlusion, causes tension on one side of the tooth and compression on the other side of the tooth. This is believed to cause V-shaped depressions on the side under tension and C-shaped depressions on the side under compression. When tooth destruction occurs at the roots of teeth, the process is referred to as internal resorption, when caused by cells within the pulp, or external resorption, when caused by cells in the periodontal ligament. ### Discoloration Discoloration of teeth may result from bacteria stains, tobacco, tea, coffee, foods with an abundance of chlorophyll, restorative materials, and medications.[65] Stains from bacteria may cause colors varying from green to black to orange. Green stains also result from foods with chlorophyll or excessive exposure to copper or nickel. Amalgam, a common dental restorative material, may turn adjacent areas of teeth black or gray. Chlorhexidine, a mouthwash, is associated with causing yellow-brown stains near the gingiva on teeth. Systemic disorders also can cause tooth discoloration. Congenital erythropoietic porphyria causes porphyrins to be deposited in teeth, causing a red-brown coloration. Blue discoloration may occur with alkaptonuria and rarely with Parkinson's disease. Erythroblastosis fetalis and biliary atresia are diseases which may cause teeth to appear green from the deposition of biliverdin. Also, trauma may change a tooth to a pink, yellow, or dark gray color. Pink and red discolorations are also associated in patients with lepromatous leprosy. Some medications, such as tetracycline antibiotics, may become incorporated into the structure of a tooth, causing intrinsic staining of the teeth. ### Alteration of eruption Tooth eruption may be altered by some environmental factors. When eruption is prematurely stopped, the tooth is said to be impacted. The most common cause of tooth impaction is lack of space in the mouth for the tooth.[66] Other causes may be tumors, cysts, trauma, and thickened bone or soft tissue. Ankylosis of a tooth occurs when the tooth has already erupted into the mouth but the cementum or dentin has fused with the alveolar bone. This may cause a person to retain their primary tooth instead of having it replaced by a permanent one. A technique for altering the natural progression of eruption is employed by orthodontists who wish to delay or speed up the eruption of certain teeth for reasons of space maintenance or otherwise preventing crowding and/or spacing. If a primary tooth is extracted prior to the root of its succeeding permanent tooth reaching ⅓ of its total growth, the eruption of the permanent tooth will be delayed. Conversely, if the roots of the permanent tooth are more than ⅔ complete, the eruption of the permanent tooth will be accelerated. Between ⅓ and ⅔, it is unknown exactly what will occur to the speed of eruption. ## Developmental ### Abnormality in number Anodontia is the total lack of tooth development. Hyperdontia is the presence of a higher-than-normal number of teeth, where as Hypodontia is the lack of some teeth. Usually, hypodontia refers to the lack of development of one or more teeth, and oligodontia may be used to describe the absence of 6 or more teeth. Some systemic disorders which may result in hyperdontia include Apert syndrome, Cleidocranial dysostosis, Crouzon syndrome, Ehlers-Danlos syndrome, Gardner syndrome, and Sturge-Weber syndrome.[67] Some systemic disorders which may result in hypodontia include Crouzon syndrome, Ectodermal dysplasia, Ehlers-Danlos syndrome, and Gorlin syndrome.[68] ### Abnormality in size Microdontia is a condition where teeth are smaller than the usual size, and macrodontia is where teeth are larger than the usual size. Microdontia of a single tooth is more likely to occur in a maxillary lateral incisor. The second most likely tooth to have microdontia are third molars. Macrodontia of all the teeth is known to occur in pituitary gigantism and pineal hyperplasia. It may also occur on one side of the face in cases of hemifacial hyperplasia. ### Abnormality in shape Gemination occurs when a developing tooth incompletely splits into the formation of two teeth. Fusion is the union of two adjacent teeth during development. Concrescence is the fusion of two separate teeth only in their cementum. Accessory cusps are additional cusps on a tooth and may manifest as a Talon cusp, Cusp of Carabelli, or Dens evaginatus. Dens invaginatus, also called Dens in dente, is a deep invagination in a tooth causing the appearance of a tooth within a tooth. Ectopic enamel is enamel found in an unusual location, such as the root of a tooth. Taurodontism is a condition where the body of the tooth and pulp chamber is enlarged, and is associated with Klinefelter syndrome, Tricho-dento-osseous syndrome, Triple X syndrome, and XYY syndrome.[69] Hypercementosis is excessive formation of cementum, which may result from trauma, inflammation, acromegaly, rheumatic fever, and Paget's disease of bone.[69] A dilaceration is a bend in the root which may have been caused by trauma to the tooth during formation. Supernumerary roots is the presence of a greater number of roots on a tooth than expected. ### Abnormality in structure Amelogenesis imperfecta is a condition in which enamel does not form properly or at all.[70] Dentinogenesis imperfecta is a condition in which dentin does not form properly and is sometimes associated with osteogenesis imperfecta.[71] Dentin dysplasia is a disorder in which the roots and pulp of teeth may be affected. Regional odontodysplasia is a disorder affecting enamel, dentin, and pulp and causes the teeth to appear "ghostly" on radiographs.[72] # In animals Teeth vary greatly among animals. Some animals, such as turtles and tortoises, are toothless. Others, such as sharks, may go through many teeth in their lifetime. Walrus tusks are canine teeth that grow continuously throughout life.[73] Dog teeth are less likely than human teeth to form dental caries because of the very high pH of dog saliva, which prevents enamel from demineralizing.[74] Unlike humans whose ameloblasts die after tooth development, rodents continually produce enamel and must wear down their teeth by gnawing on various materials.[75] Horse teeth include twelve premolars, twelve molars, and twelve incisors. The structure of horse teeth is different from human teeth as the enamel and dentin layers are intertwined.[76]	https://www.wikidoc.org/index.php/Tooth
42485d0ca5abeea3fa6e30ba5d3c3332a0754841	wikidoc	Torso	Torso # Overview Torso is an anatomical term for the central part of the many animal bodies (including that of the human) from which extend the neck and limbs. It is sometimes referred to as the trunk. The torso includes the thorax and abdomen. # Anatomy ## Major organs Most critical organs are housed within the torso. In the upper chest, the heart and lungs are protected by the rib cage, and the abdomen contains the majority of organs responsible for digestion: the liver, which respectively produces bile necessary for digestion; the large and small intestines, which extract nutrients from food; the anus, from which fecal wastes are excreted; the rectum, which stores feces; the gallbladder, which stores and concentrates bile and produces chyme; the ureters, which passes urine to the bladder; the bladder, which stores urine; and the urethra, which excretes urine and passes sperm through the seminal vesicles. Finally, the pelvic region houses both the male and female reproductive organs. ## Major muscle groups The torso also harbours many of the main muscle groups of the body, including the: - pectoral muscles - abdominal muscles - lateral muscle ## Innervation The organs and muscles etc. are innervated by various nerves, mainly originating from thoracic vertebral segments. For instance, the cutaneous innervation is provided by: - Ventral cutaneous branches - Lateral cutaneous branches - Dorsal cutaneous branches	Torso Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] # Overview Torso is an anatomical term for the central part of the many animal bodies (including that of the human) from which extend the neck and limbs. It is sometimes referred to as the trunk. The torso includes the thorax and abdomen. # Anatomy ## Major organs Most critical organs are housed within the torso. In the upper chest, the heart and lungs are protected by the rib cage, and the abdomen contains the majority of organs responsible for digestion: the liver, which respectively produces bile necessary for digestion; the large and small intestines, which extract nutrients from food; the anus, from which fecal wastes are excreted; the rectum, which stores feces; the gallbladder, which stores and concentrates bile and produces chyme; the ureters, which passes urine to the bladder; the bladder, which stores urine; and the urethra, which excretes urine and passes sperm through the seminal vesicles. Finally, the pelvic region houses both the male and female reproductive organs. ## Major muscle groups The torso also harbours many of the main muscle groups of the body, including the: - pectoral muscles - abdominal muscles - lateral muscle ## Innervation The organs and muscles etc. are innervated by various nerves, mainly originating from thoracic vertebral segments. For instance, the cutaneous innervation is provided by: - Ventral cutaneous branches - Lateral cutaneous branches - Dorsal cutaneous branches	https://www.wikidoc.org/index.php/Torso
cc404421a4a16fdec165693c62262474722e8f6f	wikidoc	Troya	Troya Troya is a brand of hand-made premium cigar owned by Lignum-2, Inc.. The brand was originally a Cuban brand, established in 1932, but the Cuban version is now offered only as an all-machine-made brand of only two vitolas. # History and Background This non-Cuban version of the Troya brand was introduced into the U. S. market in 1985. The original medium-bodied blend was discontinued in 2003 and was replaced with a mild blend in 2004. The line was further extended in 2004 with the introduction of a full-bodied cigar, the Troya X-Tra. Early 2007 saw the introduction of the Troya Clasico, a cigar blended and manufactured by Don Pepin Garcia at Tabacalera Cubana in Estelí, Nicaragua. Don Pepin had been called upon earlier to aid in the development of the blends for both of the other Troya lines, which were the result of the efforts of several people. # Troya This line is manufactured in the Dominican Republic. ## Description This line comes in two ranges, one with a Cameroon wrapper and the other with a Connecticut wrapper. The Cameroon is a medium-bodied cigar, while the Connecticut is a mild to medium cigar. The filler and binder in both are Dominican Piloto Cubano and Olor tobaccos. The cigars are presented in boxes of 24. ## Models/Vitolas # Troya X-Tra Formerly made in Estelí, Nicaragua, this line is now manufactured in the Dominican Republic at the same factory as the Troya line above. ## Description Although now made in the Dominican Republic, this line is a Nicaraguan puro. The X-Tra is a medium to full-bodied cigar. The filler is Criollo leaves, and the binder and wrapper are Corojo 99 from the Jalapá valley of Nicaragua. The cigars are presented in boxes of 24. ## Models/Vitolas # Troya Clasico This line was introduced to the U. S. market in January of 2007 as a limited edition release. The cigar was blended by Don Pepin Garcia and is manufactured at Tabacalera Cubana in Estelí, Nicaragua. ## Description This full-bodied cigar is a Nicaraguan puro using tobaccos grown in the Jalapá region of Nicaragua. The wrapper is a Corojo Oscuro and surround a binder and filler of Corojo and Criollo. It is offered in boxes of 20 cigars. ## Models/Vitolas # Notes - ↑ Profile of Cuban Troya Perelman's Cyclopedia of Havana Cigars (online version). - ↑ Jump up to: 2.0 2.1 2.2 2.3 Pereleman, Richard B., comp. Perelman's Pocket Cyclopedia of Cigars, 2007 edn. Los Angeles: Perelman, Pioneer & Co., (2006), p. 500. - ↑ Press release, Lignum-2, Inc., March 2007. - ↑ Jump up to: 4.0 4.1 4.2 Tom Irwin, Marketing Manager, Lignum-2, Inc. In litt., 3/23/2007. no:Troya	Troya Troya is a brand of hand-made premium cigar owned by Lignum-2, Inc.. The brand was originally a Cuban brand, established in 1932, but the Cuban version is now offered only as an all-machine-made brand of only two vitolas.[1] # History and Background This non-Cuban version of the Troya brand was introduced into the U. S. market in 1985.[2] The original medium-bodied blend was discontinued in 2003 and was replaced with a mild blend in 2004.[2] The line was further extended in 2004 with the introduction of a full-bodied cigar, the Troya X-Tra.[2] Early 2007 saw the introduction of the Troya Clasico, a cigar blended and manufactured by Don Pepin Garcia at Tabacalera Cubana in Estelí, Nicaragua.[3] Don Pepin had been called upon earlier to aid in the development of the blends for both of the other Troya lines, which were the result of the efforts of several people.[4] # Troya This line is manufactured in the Dominican Republic. ## Description This line comes in two ranges, one with a Cameroon wrapper and the other with a Connecticut wrapper. The Cameroon is a medium-bodied cigar, while the Connecticut is a mild to medium cigar. The filler and binder in both are Dominican Piloto Cubano and Olor tobaccos. The cigars are presented in boxes of 24. ## Models/Vitolas # Troya X-Tra Formerly made in Estelí, Nicaragua[2], this line is now manufactured in the Dominican Republic at the same factory as the Troya line above.[4] ## Description Although now made in the Dominican Republic, this line is a Nicaraguan puro. The X-Tra is a medium to full-bodied cigar. The filler is Criollo leaves, and the binder and wrapper are Corojo 99 from the Jalapá valley of Nicaragua. The cigars are presented in boxes of 24. ## Models/Vitolas # Troya Clasico This line was introduced to the U. S. market in January of 2007 as a limited edition release. The cigar was blended by Don Pepin Garcia and is manufactured at Tabacalera Cubana in Estelí, Nicaragua. ## Description This full-bodied cigar is a Nicaraguan puro using tobaccos grown in the Jalapá region of Nicaragua. The wrapper is a Corojo Oscuro and surround a binder and filler of Corojo and Criollo.[4] It is offered in boxes of 20 cigars. ## Models/Vitolas # Notes - ↑ Profile of Cuban Troya Perelman's Cyclopedia of Havana Cigars (online version). - ↑ Jump up to: 2.0 2.1 2.2 2.3 Pereleman, Richard B., comp. Perelman's Pocket Cyclopedia of Cigars, 2007 edn. Los Angeles: Perelman, Pioneer & Co., (2006), p. 500. - ↑ Press release, Lignum-2, Inc., March 2007. - ↑ Jump up to: 4.0 4.1 4.2 Tom Irwin, Marketing Manager, Lignum-2, Inc. In litt., 3/23/2007. no:Troya	https://www.wikidoc.org/index.php/Troya
8f725825ef1f432297f5a4b9a3d5dd82ab5ad004	wikidoc	Tsuga	Tsuga Tsuga (from Template:Lang-ja, 栂; the name for Tsuga sieboldii ) is a genus of conifers in the family Pinaceae. The common name hemlock is derived from a perceived similarity in the smell of the crushed foliage to that of the unrelated herb poison hemlock; see hemlock for other senses of the word. Unlike the herb, the species of Tsuga are not poisonous. There are between eight and ten species within the genus depending on the authority, with four occurring in North America and four to six in eastern Asia. # Description They are medium-sized to large evergreen trees, ranging from 20–60(–79) m tall, with a conical to irregular crown, with the latter occurring especially in some of the Asian species. The leading shoots generally droop. The bark is scaly and commonly deeply furrowed, with the colour ranging from grey to brown. The branches stem horizontally from the trunk and are usually arranged in flattened sprays that bend downward towards their tips. Short spur shoots, which are present in many gymnosperms, are weakly to moderately developed. The young twigs as well as the distal portions of stem are flexible and often pendent. The stems are rough due to pulvini that persist after the leaves fall. The winter buds are ovoid or globose, usually rounded at the apex and not resinous. The leaves are flattened to slightly angular and range from 5–35 mm long and 1–3 mm broad. They are borne singly and are arranged spirally on the stem; the leaf bases are twisted so the leaves lie flat either side of the stem or more rarely radially. Towards the base the leaves narrow abruptly to a petiole set on a forward-angled, pulvinus. The petiole is twisted at the base so that it is almost parallel with the stem. The leaf apex is either notched, rounded, or acute. The undersides have two white stomatal bands (in T. mertensiana they are inconspicuous) separated by an elevated midvein. The upper surface of the leaves lack stomata, except in T. mertensiana. They have one resin canal that is present beneath the single vascular bundle. The pollen cones grow solitary from lateral buds. They are 3–5(–10) mm long, ovoid, globose, or ellipsoid, and yellowish-white to pale purple, and borne on a short peduncle. The pollen itself has a saccate, ring-like structure at its distal pole, and rarely this structure can be more or less doubly saccate. The seed cones are borne on year-old twigs and are small ovoid-globose or oblong-cylindric, ranging from 15–40 mm long, except in T. mertensiana, where they are cylindrical and longer, 35–80 mm in length; they are solitary, terminal or rarely lateral, pendulous, and are sessile or on a short peduncle up to 4 mm long. Maturation occurs in 5–8 months, and the seeds are shed shortly thereafter; the cones are shed soon after seed release or up to a year or two later. The seed scales are thin, leathery and persistent. They vary in shape and lack an apophysis and an umbo. The bracts are included and small. The seeds are small, from 2 to 4 mm long, and winged, with the winge being 8 to 12 mm in length. They also contain small adaxial resin vesicles. Seed germination is epigeal; the seedlings have four to six cotyledons. # Taxonomy Mountain Hemlock T. mertensiana is unusual in the genus in several respects. The leaves are less flattened and arranged all round the shoot, and have stomata above as well as below, giving the foliage a glaucous colour; and the cones are the longest in the genus, 35-80 mm long and cylindrical rather than ovoid. Some botanists treat it in a distinct genus as Hesperopeuce mertensiana (Bong.) Rydb., though it is more generally only considered distinct at the rank of subgenus. Another species, Bristlecone Hemlock, first described as Tsuga longibracteata, is now treated in a distinct genus Nothotsuga; it differs from Tsuga in the erect (not pendulous) cones with exserted bracts, and male cones clustered in umbels, in these features more closely allied to the genus Keteleeria. # Ecology The species are all adapted to (and are confined to) relatively moist cool temperate areas with high rainfall, cool summers, and little or no water stress; they are also adapted to cope with heavy to very heavy winter snowfall and tolerate ice storms better than most other trees. # Threats The two eastern North American species, T. canadensis and T. caroliniana are under serious threat by the sap-sucking insect Adelges tsugae (Hemlock Woolly Adelgid). This adelgid, related to the aphids, was introduced accidentally from eastern Asia, where it is only a minor pest. Extensive mortality has occurred, particularly east of the Appalachian Mountains. The Asian species are resistant to this pest, and the two western American hemlocks, are moderately resistant. Tsuga species are also used as food plants by the larvae of some Lepidoptera species including Autumnal Moth and The Engrailed, and older caterpillars of the Gypsy Moth. The foliage of young trees is often browsed by deer, and the seeds are eaten by finches and small rodents. Old trees are commonly attacked by various fungal disease and decay species, notably Heterobasidion annosum and Armillaria species, which rot the heartwood and eventually leave the tree liable to windthrow, and Rhizina undulata, which may kill groups of trees following minor grass fires which activate growth of the Rhizina spores. # Uses The wood obtained from hemlocks is important in the timber industry, especially for use as wood pulp. Many species are utilised in horticulture, and numerous cultivars have been selected for use in gardens.	Tsuga Tsuga (from Template:Lang-ja, 栂; the name for Tsuga sieboldii ) is a genus of conifers in the family Pinaceae. The common name hemlock is derived from a perceived similarity in the smell of the crushed foliage to that of the unrelated herb poison hemlock; see hemlock for other senses of the word. Unlike the herb, the species of Tsuga are not poisonous. There are between eight and ten species within the genus depending on the authority, with four occurring in North America and four to six in eastern Asia.[1][2][3][4][5] # Description They are medium-sized to large evergreen trees, ranging from 20–60(–79) m tall, with a conical to irregular crown, with the latter occurring especially in some of the Asian species. The leading shoots generally droop. The bark is scaly and commonly deeply furrowed, with the colour ranging from grey to brown. The branches stem horizontally from the trunk and are usually arranged in flattened sprays that bend downward towards their tips. Short spur shoots, which are present in many gymnosperms, are weakly to moderately developed. The young twigs as well as the distal portions of stem are flexible and often pendent. The stems are rough due to pulvini that persist after the leaves fall. The winter buds are ovoid or globose, usually rounded at the apex and not resinous. The leaves are flattened to slightly angular and range from 5–35 mm long and 1–3 mm broad. They are borne singly and are arranged spirally on the stem; the leaf bases are twisted so the leaves lie flat either side of the stem or more rarely radially. Towards the base the leaves narrow abruptly to a petiole set on a forward-angled, pulvinus. The petiole is twisted at the base so that it is almost parallel with the stem. The leaf apex is either notched, rounded, or acute. The undersides have two white stomatal bands (in T. mertensiana they are inconspicuous) separated by an elevated midvein. The upper surface of the leaves lack stomata, except in T. mertensiana. They have one resin canal that is present beneath the single vascular bundle.[1][2][3][4][5] The pollen cones grow solitary from lateral buds. They are 3–5(–10) mm long, ovoid, globose, or ellipsoid, and yellowish-white to pale purple, and borne on a short peduncle. The pollen itself has a saccate, ring-like structure at its distal pole, and rarely this structure can be more or less doubly saccate. The seed cones are borne on year-old twigs and are small ovoid-globose or oblong-cylindric, ranging from 15–40 mm long, except in T. mertensiana, where they are cylindrical and longer, 35–80 mm in length; they are solitary, terminal or rarely lateral, pendulous, and are sessile or on a short peduncle up to 4 mm long. Maturation occurs in 5–8 months, and the seeds are shed shortly thereafter; the cones are shed soon after seed release or up to a year or two later. The seed scales are thin, leathery and persistent. They vary in shape and lack an apophysis and an umbo. The bracts are included and small. The seeds are small, from 2 to 4 mm long, and winged, with the winge being 8 to 12 mm in length. They also contain small adaxial resin vesicles. Seed germination is epigeal; the seedlings have four to six cotyledons.[1][2][3][5][4] # Taxonomy Mountain Hemlock T. mertensiana is unusual in the genus in several respects. The leaves are less flattened and arranged all round the shoot, and have stomata above as well as below, giving the foliage a glaucous colour; and the cones are the longest in the genus, 35-80 mm long and cylindrical rather than ovoid. Some botanists treat it in a distinct genus as Hesperopeuce mertensiana (Bong.) Rydb.,[6] though it is more generally only considered distinct at the rank of subgenus.[1] Another species, Bristlecone Hemlock, first described as Tsuga longibracteata, is now treated in a distinct genus Nothotsuga; it differs from Tsuga in the erect (not pendulous) cones with exserted bracts, and male cones clustered in umbels, in these features more closely allied to the genus Keteleeria.[1][3] # Ecology The species are all adapted to (and are confined to) relatively moist cool temperate areas with high rainfall, cool summers, and little or no water stress; they are also adapted to cope with heavy to very heavy winter snowfall and tolerate ice storms better than most other trees.[1][3] # Threats The two eastern North American species, T. canadensis and T. caroliniana are under serious threat by the sap-sucking insect Adelges tsugae (Hemlock Woolly Adelgid).[7] This adelgid, related to the aphids, was introduced accidentally from eastern Asia, where it is only a minor pest. Extensive mortality has occurred, particularly east of the Appalachian Mountains. The Asian species are resistant to this pest, and the two western American hemlocks, are moderately resistant. Tsuga species are also used as food plants by the larvae of some Lepidoptera species including Autumnal Moth and The Engrailed, and older caterpillars of the Gypsy Moth. The foliage of young trees is often browsed by deer, and the seeds are eaten by finches and small rodents. Old trees are commonly attacked by various fungal disease and decay species, notably Heterobasidion annosum and Armillaria species, which rot the heartwood and eventually leave the tree liable to windthrow, and Rhizina undulata, which may kill groups of trees following minor grass fires which activate growth of the Rhizina spores.[8] # Uses The wood obtained from hemlocks is important in the timber industry, especially for use as wood pulp. Many species are utilised in horticulture, and numerous cultivars have been selected for use in gardens.	https://www.wikidoc.org/index.php/Tsuga
a6a40b5d14fca002c6fc396618880088ceb74f68	wikidoc	Virus	Virus A virus (from the Latin virus meaning "toxin" or "poison"), is a sub-microscopic infectious agent that is unable to grow or reproduce outside a host cell. Each viral particle, or virion, consists of genetic material, DNA or RNA, within a protective protein coat called a capsid. The capsid shape varies from simple helical and icosahedral (polyhedral or near-spherical) forms, to more complex structures with tails or an envelope. Viruses infect cellular life forms and are grouped into animal, plant and bacterial types, according to the type of host infected. Biologists debate whether or not viruses are living organisms. Some consider them non-living as they do not meet the criteria of the definition of life. For example, unlike most organisms, viruses do not have cells. However, viruses have genes and evolve by natural selection. Others have described them as organisms at the edge of life. Viral infections in human and animal hosts usually result in an immune response and disease. Often, a virus is completely eliminated by the immune system. Antibiotics have no effect on viruses, but antiviral drugs have been developed to treat life-threatening infections. Vaccines that produce lifelong immunity can prevent viral infections. # Etymology The word is from the Latin virus referring to poison and other noxious substances, first used in English in 1392. Virulent, from Latin virulentus, "poisonous", dates to 1400. A meaning of "agent that causes infectious disease" is first recorded in 1728, before the discovery of viruses by the Russian-Ukrainian biologist Dmitry Ivanovsky in 1892. The adjective viral dates to 1948. Today, virus is used to describe the biological viruses discussed above and as a metaphor for other parasitically-reproducing things, such as memes or computer viruses (since 1972). The term virion is also used to refer to a single infective viral particle. The English plural form of virus is viruses. # Discovery of viruses Viral diseases such as rabies, yellow fever and smallpox have affected humans for centuries. There is hieroglyphical evidence of polio in ancient Egyptian medicine, though the cause of this disease was unknown at the time. In the 10th century, Muhammad ibn Zakarīya Rāzi (Rhazes) wrote the Treatise on Smallpox and Measles, in which he gave the first clear descriptions of smallpox and measles. In the 1020s, Avicenna wrote The Canon of Medicine, in which he discovered the contagious nature of infectious diseases, such as tuberculosis and sexually transmitted diseases, and their distribution through bodily contact or through water and soil; stated that bodily secretion is contaminated by "foul foreign earthly bodies" before being infected; and introduced the method of quarantine as a means of limiting the spread of contagious disease. When the Black Death bubonic plague reached al-Andalus in the 14th century, Ibn Khatima discovered that infectious diseases are caused by microorganisms which enter the human body. The etiologic cause of the bubonic plague would later be identified as a bacterium. Another 14th century Andalusian physician, Ibn al-Khatib (1313-1374), wrote a treatise called On the Plague, in which he stated how infectious diseases can be transmitted through bodily contact and "through garments, vessels and earrings." In 1717, Mary Montagu, the wife of an English ambassador to the Ottoman Empire, observed local women inoculating their children against smallpox. In the late 18th century, Edward Jenner observed and studied Miss Sarah Nelmes, a milkmaid who had previously caught cowpox and was found to be immune to smallpox, a similar, but devastating virus. Jenner developed the smallpox vaccine based on these findings. After lengthy vaccination campaigns, the World Health Organization (WHO) certified the eradication of smallpox in 1979. In the late 19th century, Charles Chamberland developed a porcelain filter with pores small enough to remove cultured bacteria from their culture medium. Dimitri Ivanovski used this filter to study an infection of tobacco plants, now known as tobacco mosaic virus. He passed crushed leaf extracts of infected tobacco plants through the filter, then used the filtered extracts to infect other plants, thereby proving that the infectious agent was not a bacterium. Similar experiments were performed by several other researchers, with similar results. These experiments showed that viruses are orders of magnitude smaller than bacteria. The term virus was coined by the Dutch microbiologist Martinus Beijerinck, who showed, using methods based on the work of Ivanovski, that tobacco mosaic disease is caused by something smaller than a bacterium. He coined the Latin phrase "contagium vivum fluidum" (which means "soluble living germ") as the first idea of the virus. The first human virus identified was Yellow Fever virus. In the early 20th century, Frederick Twort discovered that bacteria could be infected by viruses. Felix d'Herelle, working independently, showed that a preparation of viruses caused areas of cellular death on thin cell cultures spread on agar. Counting the dead areas allowed him to estimate the original number of viruses in the suspension. The invention of electron microscopy provided the first look at viruses. In 1935, Wendell Stanley crystallized the tobacco mosaic virus and found it to be mostly protein. A short time later, the virus was separated into protein and nucleic acid parts. In 1939, Max Delbrück and E.L. Ellis demonstrated that, in contrast to cellular organisms, bacteriophage reproduce in "one step", rather than exponentially. A major problem for early virologists was the inability to propagate viruses on sterile culture media, as is done with cellular microorganisms. This limitation required medical virologists to infect living animals with infectious material, which is dangerous. The first breakthrough came in 1931, when Ernest William Goodpasture demonstrated the growth of influenza and several other viruses in fertile chicken eggs. However, some viruses would not grow in chicken eggs, and a more flexible technique was needed for propagation of viruses. The solution came in 1949 when John Franklin Enders, Thomas H. Weller and Frederick Chapman Robbins together developed a technique to grow the polio virus in cultures of living animal cells. Their methods have since been extended and applied to the growth of viruses and other infectious agents that do not grow on sterile culture media. # Origins The origin of modern viruses is not entirely clear. It may be that no single mechanism can account for their origin. They do not fossilize well, so molecular techniques have been the most useful means of hypothesising how they arose. Research in microfossil identification and molecular biology may yet discern fossil evidence dating to the Archean or Proterozoic eons. Two main hypotheses currently exist. Small viruses with only a few genes may be runaway stretches of nucleic acid originating from the genome of a living organism. Their genetic material could have been derived from transferable genetic elements such as plasmids or transposons, that are prone to moving within, leaving, and entering genomes. New viruses are emerging de novo and therefore, it is not always the case that viruses have "ancestors". Viruses with larger genomes, such as poxviruses, may have once been small cells that parasitized larger host cells. Over time, genes not required by their parasitic lifestyle would have been lost in a streamlining process known as "retrograde-evolution" or "reverse-evolution". The bacteria Rickettsia and Chlamydia are living cells that, like viruses, can only reproduce inside host cells. They lend credence to the streamlining hypothesis, as their parasitic lifestyle is likely to have caused the loss of genes that enabled them to survive outside a host cell. It is possible that viruses represent a primitive form of self replicating DNA and are a precursor to life as it is currently defined. Other infectious particles which are even simpler in structure than viruses include viroids, satellites, and prions. # Classification In taxonomy, the classification of viruses is difficult owing to the lack of a fossil record and the dispute over whether they are living or non-living. They do not fit easily into any of the domains of biological classification, and classification begins at the family rank. However, the domain name of Acytota (without cells) has been suggested. This would place viruses on a par with the other domains of Eubacteria, Archaea, and Eukarya. Not all families are currently classified into orders, nor all genera classified into families. In 1962, André Lwoff, Robert Horne, and Paul Tournier were the first to develop a means of virus classification, based on the Linnaean hierarchical system. This system based classification on phylum, class, order, family, genus, and species. Viruses were grouped according to their shared properties (not of their hosts) and the type of nucleic acid forming their genomes. Following this initial system, a few modifications were made and the International Committee on Taxonomy of Viruses was developed (ICTV). ### ICTV classification The International Committee on Taxonomy of Viruses (ICTV) developed the current classification system and put in place guidelines that put a greater weighting on certain virus properties to maintain family uniformity. A universal system for classifying viruses, and a unified taxonomy, has been established since 1966. In determining order, taxonomists should consider the type of nucleic acid present, whether the nucleic acid is single- or double-stranded, and the presence or absence of an envelope. After these three main properties, other characteristics can be considered: the type of host, the capsid shape, immunological properties and the type of disease it causes. The system makes use of a series of ranked taxons. The general structure is as follows: The recognition of orders is very recent; to date, only three have been named, and most families remain unplaced. The committee does not formally distinguish between subspecies, strains, and isolates. In total there are three orders, 56 families, nine subfamilies, and 233 genera. ICTV recognizes about 1,550 virus species, but about 30,000 virus strains and isolates are being tracked by virologists. The Nobel Prize-winning biologist David Baltimore devised the Baltimore classification system. The ICTV classification system is used in conjunction with the Baltimore classification system in modern virus classification. ### Baltimore Classification The Baltimore classification of viruses is based on the mechanism of mRNA production. Viruses must generate positive strand mRNAs from their genomes to produce proteins and replicate themselves, but different mechanisms are used to achieve this in each virus family. This classification places viruses into seven groups: As an example of viral classification, the chicken pox virus, Varicella zoster (VZV), belongs to family Herpesviridae, subfamily Alphaherpesvirinae and genus Varicellovirus. It remains unranked in terms of order. VZV is in Group I of the Baltimore Classification because it is a dsDNA virus that does not use reverse transcriptase. # Structure A complete virus particle, known as a virion, consists of nucleic acid surrounded by a protective coat of protein called a capsid. Viruses can have a lipid "envelope" derived from the host cell membrane. A capsid is made from proteins encoded by the viral genome and its shape serves as the basis for morphological and antigenic distinction. Virally coded protein subunits will self-assemble to form a capsid, generally requiring the presence of the virus genome. However, complex viruses code for proteins which assist in the construction of their capsid. Proteins associated with nucleic acid are known as nucleoproteins, and the association of viral capsid proteins with viral nucleic acid is called a nucleocapsid. In general, there are four main morphological virus types: ## Electron microscopy Electron microscopy is the most common method used to study the morphology of viruses. To increase the contrast between viruses and the background, electron-dense "stains" are used. These are solutions of salts of heavy metals such as tungsten, that scatter the electrons from regions covered with the stain. When virus particles are coated with stain (positive staining), fine detail is obscured. Negative staining overcomes this problem by staining the background only. ## Size A medium-sized virion next to a flea is roughly equivalent to a human next to a mountain twice the size of Mount Everest. Some filoviruses have a total length of up to 1400 nm, however their capsid diameters are only about 80 nm. Most viruses which have been studied have a capsid diameter between 10 and 300 nanometres. Most viruses are unable to be seen with a light microscope but some are as large or larger than the smallest bacteria and can be seen under high optical magnification. More commonly, both scanning and transmission electron microscopes are used to visualize virus particles. # Genome An enormous variety of genomic structures can be seen among viral species; as a group they contain more structural genomic diversity than the entire kingdoms of either plants, animals, or bacteria. ## Nucleic acid A virus may employ either DNA or RNA as the nucleic acid. Rarely do they contain both, however cytomegalovirus is an exception to this, possessing a DNA core with several mRNA segments. By far most viruses have RNA. Plant viruses tend to have single-stranded RNA and bacteriophages tend to have double-stranded DNA. Some virus species possess abnormal nucleotides, such as hydroxymethylcytosine instead of cytosine, as a normal part of their genome. ## Shape Viral genomes may be circular, such as polyomaviruses, or linear, such as adenoviruses. The type of nucleic acid is irrelevant to the shape of the genome. Among RNA viruses, the genome is often divided up into separate parts within the virion and are called segmented. Double-stranded RNA genomes and some single-stranded RNA genomes are segmented. Each segment often codes for one protein and they are usually found together in one capsid. Every segment is not required to be in the same virion for the overall virus to be infectious, as demonstrated by the brome mosaic virus. ## Strandedness A viral genome, irrespective of nucleic acid type, may be either single-stranded or double-stranded. Single-stranded genomes consist of an unpaired nucleic acid, analogous to one-half of a ladder split down the middle. Double-stranded genomes consist of 2 complementary paired nucleic acids, analogous to a ladder. Viruses, such as those belonging to the Hepadnaviridae, contain a genome which is partially double-stranded and partially single-stranded. Viruses that infect humans include double-stranded RNA (e.g. Rotavirus), single-stranded RNA (e.g. Influenza virus), single-stranded DNA (e.g. Parvovirus B19) and double-stranded DNA (Herpes virus). ## Sense For viruses with RNA as their nucleic acid, the strands are said to be either positive-sense (called the plus-strand) or negative-sense (called the minus-strand), depending on whether it is complementary to viral mRNA. Positive-sense viral RNA is identical to viral mRNA and thus can be immediately translated by the host cell. Negative-sense viral RNA is complementary to mRNA and thus must be converted to positive-sense RNA by an RNA polymerase before translation. DNA nomenclature is similar to RNA nomenclature, in that the coding strand for the viral mRNA is complementary to it (-), and the non-coding strand is a copy of it (+). ## Genome size Genome size in terms of the weight of nucleotides varies between species. The smallest genomes code for only four proteins and weigh about 106 Daltons, the largest weigh about 108 Daltons and code for over one hundred proteins. RNA viruses generally have smaller genome sizes than DNA viruses due to a higher error-rate when replicating, resulting in a maximum upper size limit. Beyond this limit, errors in the genome when replicating render the virus useless or uncompetitive. To compensate for this, RNA viruses often have segmented genomes where the genome is split into smaller molecules, thus reducing the chance of error. In contrast, DNA viruses generally have larger genomes due to the high fidelity of their replication enzymes. ## Gene reassortment There is an evolutionary advantage in having a segmented genome. Different strains of a virus with a segmented genome, from a pig or a bird or a human for example, such as Influenza virus, can shuffle and combine with other genes producing progeny viruses or (offspring) that have unique characteristics. This is called reassortment or viral sex. This is one reason why Influenza virus constantly changes. ## Genetic recombination Genetic recombination is the process by which a strand of DNA is broken and then joined to the end of a different DNA molecule. This can occur when viruses infect cells simultaneously and studies of viral evolution have shown that recombination has been rampant in the species studied. Recombination is common to both RNA and DNA viruses. ## Genetic change Viruses undergo genetic change by several mechanisms. These include a process called genetic drift where individual bases in the DNA or RNA mutate to other bases. Most of these point mutations are silent in that they do not change the protein that the gene encodes, but others can confer evolutionary advantages such as resistance to antiviral drugs. Antigenic shift is where there is a major change in the genome of the virus. This occurs as a result of recombination or reassortment (see above). When this happens with influenza viruses, pandemics may result. By genome rearrangement the structure of the gene changes although no mutations have necessarily occurred. RNA viruses are much more likely to mutate than DNA viruses for the reasons outlined above. Viruses often exist as quasispecies or swarms of viruses of the same species but with slightly different genome nucleoside sequences. Such quasispecies are a prime target for natural selection. # Replication Viral populations do not grow through cell division, because they are acellular; instead, they use the machinery and metabolism of a host cell to produce multiple copies of themselves. A virus can still cause degenerative effects within a cell without causing its death; collectively these are termed cytopathic effects. ## Virus life cycle The life cycle of viruses differs greatly between species (see below) but there are six basic stages in the life cycle of viruses: - Attachment is a specific binding between viral capsid proteins and specific receptors on the host cellular surface. This specificity determines the host range of a virus. For example, the human immunodeficiency virus (HIV) infects only human T cells, because its surface protein, gp120, can interact with CD4 and receptors on the T cell's surface. This mechanism has evolved to favour those viruses that only infect cells that they are capable of replicating in. Attachment to the receptor can induce the viral-envelope protein to undergo changes that results in the fusion of viral and cellular membranes. - Penetration: following attachment, viruses enter the host cell through receptor mediated endocytosis or membrane fusion. - Uncoating is a process in which the viral capsid is degraded by viral enzymes or host enzymes thus releasing the viral genomic nucleic acid. - Replication involves synthesis of viral messenger RNA (mRNA) for viruses except positive sense RNA viruses (see above), viral protein synthesis and assembly of viral proteins and viral genome replication. - Following the assembly of the virus particles post-translational modification of the viral proteins often occurs. In viruses such as HIV, this modification, (sometimes called maturation), occurs after the virus has been released from the host cell. - Viruses are released from the host cell by lysis (see below). Enveloped viruses (e.g., HIV) typically are released from the host cell by budding. During this process, the virus acquires its phospholipid envelope which contains embedded viral glycoproteins. ### DNA viruses Animal DNA viruses, such as herpesviruses, enter the host via endocytosis, the process by which cells take in material from the external environment. Frequently after a chance collision with an appropriate surface receptor on a cell, the virus penetrates the cell, the viral genome is released from the capsid, and host polymerases begin transcribing viral mRNA. New virions are assembled and released either by cell lysis or by budding off the cell membrane. ### RNA viruses Animal RNA viruses can be placed into about four different groups depending on their modes of replication. The polarity of the RNA largely determines the replicative mechanism, as well as whether the genetic material is single-stranded or double-stranded. Some RNA viruses are actually DNA-based but use an RNA-intermediate to replicate. RNA viruses are dependent on virally encoded RNA replicase to create copies of their genomes. ### Reverse transcribing viruses Reverse transcribing viruses replicate using reverse transcription, which is the formation of DNA from an RNA template. Reverse transcribing viruses containing RNA genomes use a DNA intermediate to replicate, whereas those containing DNA genomes use an RNA intermediate during genome replication. Both types use the reverse transcriptase enzyme to carry out the nucleic acid conversion. Both types are susceptible to antiviral drugs that inhibit the reverse transcriptase enzyme, e.g. zidovudine and lamivudine. An example of the first type is HIV which is a retrovirus. Retroviruses often integrate the DNA produced by reverse transcription into the host genome. This is why HIV infection can at present, only be treated and not cured. Examples of the second type are the Hepadnaviridae, which includes the Hepatitis B virus and the Caulimoviridae - e.g. Cauliflower mosaic virus. ### Bacteriophages Bacteriophages infect specific bacteria by binding to surface receptor molecules and then enter the cell. Within a short amount of time, in some cases, just minutes, bacterial polymerase starts translating viral mRNA into protein. These proteins go on to become either new virions within the cell, helper proteins which help assembly of new virions, or proteins involved in cell lysis. Viral enzymes aid in the breakdown of the cell membrane, and in the case of the T4 phage, in just over twenty minutes after injection over three hundred phages could be released. # Lifeform debate Viruses have been described as "organisms at the edge of life", but argument continues over whether viruses are truly alive. According to the United States Code they are considered microorganisms in the sense of biological weaponry and malicious use. Scientists, however, are divided. Things become more complicated as they look at viroids and prions. Viruses resemble other organisms in that they possess genes and can evolve in infected cells by natural selection. They can reproduce by creating multiple copies of themselves through self-assembly. Viruses do not have a cell structure (regarded as the basic unit of life), although they do have genes. Additionally, although they reproduce, they do not self-metabolize and require a host cell to replicate and synthesize new products. However, bacterial species such as Rickettsia and Chlamydia are considered living organisms but are unable to reproduce outside a host cell. An argument can be made that accepted forms of life use cell division to reproduce, whereas viruses spontaneously assemble within cells. The comparison is drawn between viral self-assembly and the autonomous growth of non-living crystals. Virus self-assembly within host cells has implications for the study of the origin of life, as it lends credence to the hypothesis that life could have started as self-assembling organic molecules. If viruses are considered alive, then the criteria specifying life will have to exclude the cell. If viruses are said to be alive, the question could follow of whether even smaller infectious particles, such as viroids and prions, are alive. # Viruses and disease Examples of common human diseases caused by viruses include the common cold, the flu, chickenpox and cold sores. Serious diseases such as Ebola, AIDS, avian influenza and SARS are caused by viruses. The relative ability of viruses to cause disease is described in terms of virulence. Other diseases are under investigation as to whether they too have a virus as the causative agent, such as the possible connection between Human Herpesvirus Six (HHV6) and neurological diseases such as multiple sclerosis and chronic fatigue syndrome. There is current controversy over whether the borna virus, previously thought of as causing neurological diseases in horses, could be responsible for psychiatric illnesses in humans. Viruses have different mechanisms by which they produce disease in an organism, which largely depends on the species. Mechanisms at the cellular level primarily include cell lysis, the breaking open and subsequent death of the cell. In multicellular organisms, if enough cells die the whole organism will start to suffer the effects. Although viruses cause disruption of healthy homeostasis, resulting in disease, they may exist relatively harmlessly within an organism. An example would include the ability of the herpes simplex virus, which cause cold sores, to remain in a dormant state within the human body. This is called latency and is a characteristic of the herpes viruses including the Epstein-Barr virus, which causes glandular fever, and the Varicella zoster virus, which causes chicken pox. Latent chickenpox infections return in later life as the disease called shingles. Some viruses can cause life-long or chronic infections, where the viruses continue to replicate in the body despite the hosts' defense mechanisms. This is common in Hepatitis B virus and Hepatitis C Virus infections. People chronically infected with the Hepatitis B virus are known as carriers who serve as reservoirs of infectious virus. In some populations, with a high proportion of carriers, the disease is said to be endemic. When diagnosing Hepatitis B virus infections, it is important to distinguish between acute and chronic infections. ## Epidemiology Viral epidemiology is the branch of medical science dealing with the transmission and control of virus infections in humans. Transmission of viruses can be vertical, that is from mother to child, or horizontal, which means from person to person. Examples of vertical transmission include Hepatitis B virus and HIV where the baby is born already infected with the virus. Another, more rare, example is the Varicella zoster virus, which although causing relatively mild infections in humans, can be fatal to the foetus and newly born baby. Horizontal transmission is the most common mechanism of spread of viruses in populations. Transmission can be exchange of blood by sexual activity, e.g. HIV, Hepatitis B and Hepatitis C; by mouth by exchange of saliva, e.g. Epstein-Barr virus, or from contaminated food or water, e.g. Norovirus; by breathing in viruses in the form of aerosols, e.g. Influenza virus; and by insect vectors such as mosquitoes, e.g. dengue. The rate or speed of transmission of viral infections depends on factors that include population density, the number of susceptible individuals, (i.e. those who are not immune), the quality of health care and the weather. ## Epidemics and pandemics Native American populations were devastated by contagious diseases, particularly smallpox, brought to the Americas by European colonists. It is unclear how many Native Americans were killed by foreign diseases after the arrival of Columbus in the Americas, but the numbers have been estimated to be close to 70% of the indigenous population. The damage done by this disease significantly aided European attempts to displace and conquer the native population. A pandemic is a world-wide epidemic. The 1918 flu pandemic, commonly referred to as the Spanish flu, was a category 5 influenza pandemic caused by an unusually severe and deadly Influenza A virus. The victims were often healthy young adults, in contrast to most influenza outbreaks which predominantly affect juvenile, elderly, or otherwise weakened patients. The Spanish flu pandemic lasted from 1918 to 1919. Older estimates say it killed 40–50 million people, while more recent research suggests that it may have killed as many as 100 million people, or 5% of the world's population in 1918. Most researchers believe that HIV originated in sub-Saharan Africa during the twentieth century; it is now a pandemic, with an estimated 38.6 million people now living with the disease worldwide. As of January 2006, the Joint United Nations Programme on HIV/AIDS (UNAIDS) and the World Health Organization (WHO) estimate that AIDS has killed more than 25 million people since it was first recognized on June 5, 1981, making it one of the most destructive epidemics in recorded history. Several highly lethal viral pathogens are members of the Filoviridae. Filoviruses are filament-like viruses that cause viral hemorrhagic fever, and include the Ebola and Marburg viruses. The Marburg virus attracted widespread press attention in April 2005 for an outbreak in Angola. Beginning in October 2004 and continuing into 2005, the outbreak was the world's worst epidemic of any kind of viral hemorrhagic fever. ## Viruses and cancer Viruses are an established cause of malignancy in humans and other species. The main viruses associated with human cancers are human papillomavirus, hepatitis B and hepatitis C virus, Epstein-Barr virus, and human T-lymphotropic virus. Hepatitis viruses, including hepatitis B and hepatitis C, can induce a chronic viral infection that leads to liver cancer. Infection by human T-lymphotropic virus can lead to tropical spastic paraparesis and adult T-cell leukemia. Human papillomaviruses are an established cause of cancers of cervix, skin, anus, and penis. Within the Herpesviridae, Kaposi's sarcoma-associated herpesvirus causes Kaposi's sarcoma and body cavity lymphoma, and Epstein–Barr virus causes Burkitt's lymphoma, Hodgkin’s lymphoma, B lymphoproliferative disorder and nasopharyngeal carcinoma. ## Laboratory diagnosis In the diagnostic laboratory, virus infections are confirmed by several methods that include: - Growth of the virus in a cell culture from a specimen taken from the patient. - Detection of virus-specific IgM antibody (see below) in the blood. - Detection of virus antigens by ELISA in tissues and fluids. - Detection of virus encoded DNA and RNA by PCR. - Observation of virus particles by electron microscopy. ## Prevention and treatment Because viruses use the machinery of a host cell to reproduce and reside within them, they are difficult to eliminate without killing the host cell. The most effective medical approaches to viral diseases so far are vaccinations to provide resistance to infection, and antiviral drugs which treat the symptoms of viral infections. ## Host immune response The body's first line of defense against viruses is the innate immune system. This comprises cells and other mechanisms that defend the host from infection in a non-specific manner. This means that the cells of the innate system recognize, and respond to, pathogens in a generic way, but unlike the adaptive immune system, it does not confer long-lasting or protective immunity to the host. RNA interference is an important innate defense against viruses. Many viruses have a replication strategy that involves double-stranded RNA dsRNA. When such a virus infects a cell, it releases its RNA molecule or molecules, which immediately bind to a protein complex called Dicer that cuts the RNA into smaller pieces. A biochemical pathway called the RISC complex is activated which degrades the viral mRNA and the cell survives the infection. Rotaviruses avoid this mechanism by not uncoating fully inside the cell and by releasing newly produced mRNA through pores in the particle's inner capsid. The genomic dsRNA remains protected inside the core of the virion. When the adaptive immune system of a vertebrate encounters a virus, it produces specific antibodies which bind to the virus and render it non-infectious. This is called humoral immunity. Two types of antibodies are important. The first called IgM is highly effective at neutralizing viruses but is only produced by the cells of the immune system for a few weeks. The second, called, IgG is produced indefinitely. The presence of IgM in the blood of the host is used to test for acute infection, whereas IgG indicates an infection sometime in the past. Both types of antibodies are measured when tests for immunity are carried out. A second defense of vertebrates against viruses is called cell-mediated immunity and involves immune cells known as T cells. The body's cells constantly display short fragments of their proteins on the cell's surface, and if a T cell recognizes a suspicious viral fragment there, the host cell is destroyed by T killer cells and the virus-specific T-cells proliferate. Cells such as the macrophage are specialists at this antigen presentation. Not all virus infections produce a protective immune response in this way. HIV evades the immune system by constantly changing the amino acid sequence of the proteins on the surface of the virion. These persistent viruses evade immune control by sequestration, blockade of antigen presentation, cytokine resistance, evasion of natural killer cell activities, escape from apoptosis, and antigenic shift. Other viruses, called "neurotropic viruses", are disseminated by neural spread where the immune system may be unable to reach them. The production of interferon is an important host defense mechanism. ## Vaccines Vaccination is a cheap and effective way of preventing infections by viruses. Vaccines were used to prevent viral infections long before the discovery of the actual viruses. Their use has resulted in a dramatic decline in morbidity (illness) and mortality (death) associated with viral infections such as polio, measles, mumps and rubella. Smallpox infections have been eradicated. Currently vaccines are available to prevent over thirteen viral infections of humans, and more are used to prevent viral infections of animals. Vaccines can consist of live-attenuated or killed viruses, or viral proteins (antigens). Live vaccines contain weakened forms of the virus that causes the disease. Such viruses are called attenuated. Live vaccines can be dangerous when given to people with a weak immunity, (who are described as immunocompromised), because in these people, the weakened virus can cause the original disease. Biotechnology and genetic engineering techniques are used to produce subunit vaccines. These vaccines use only the capsid proteins of the virus. Hepatitis B vaccine is an example of this type of vaccine. Subunit vaccines are safe for immunocompromised patients because they cannot cause the disease. The Yellow Fever virus vaccine, a live-attenuated strain called 17D, is arguably the safest and most effective vaccine ever generated. ## Antiviral drugs Over the past twenty years, the development of antiviral drugs has increased rapidly. This has been driven by the AIDS epidemic. Antiviral drugs are often nucleoside analogues, (fake DNA building blocks), which viruses incorporate into their genomes during replication. The life-cycle of the virus is then halted because the newly synthesized DNA is inactive. This is because these analogues lack the hydroxyl groups which along with phosphorus atoms, link together to form the strong "backbone" of the DNA molecule. This is called DNA chain termination. Examples of nucleoside analogues are aciclovir for Herpes virus infections and lamivudine for HIV and Hepatitis B virus infections. Aciclovir is one of the oldest and most frequently prescribed antiviral drugs. Other antiviral drugs in use target different stages of the viral life cycle. HIV is dependent on a proteolytic enzyme called the HIV-1 protease for it to become fully infectious. There is a class of drugs called protease inhibitors which have been designed to inactivate the enzyme. Hepatitis C is caused by an RNA virus. In 80% of people infected, the disease is chronic, and without treatment, they are infected and infectious for the remainder of their lives. However, there is now an effective treatment using the nucleoside analogue drug ribavirin combined with interferon. The treatment of chronic carriers of the Hepatitis B virus by using a similar strategy using lamivudine is being developed. ## Notable examples The clinically most notable virus species belong to the following families: - Adenoviridae - Picornaviridae - Herpesviridae - Hepadnaviridae - Flaviviridae - Retroviridae - Orthomyxoviridae - Paramyxoviridae - Papovaviridae - Rhabdoviridae - Reoviridae - Togaviridae # Applications ## Life sciences and medicine Viruses are important to the study of molecular and cellular biology as they provide simple systems that can be used to manipulate and investigate the functions of cells. The study and use of viruses have provided valuable information about aspects of cell biology. For example, viruses have been useful in the study of genetics and helped our understanding of the basic mechanisms of molecular genetics, such as DNA replication, transcription, RNA processing, translation, protein transport, and immunology. Geneticists often use viruses as vectors to introduce genes into cells that they are studying. This is useful for making the cell produce a foreign substance, or to study the effect of introducing a new gene into the genome. In similar fashion, virotherapy uses viruses as vectors to treat various diseases, as they can specifically target cells and DNA. It shows promising use in the treatment of cancer and in gene therapy. Eastern European scientists have used phage therapy as an alternative to antibiotics for some time, and interest in this approach is increasing, due to the high level of antibiotic resistance now found in some pathogenic bacteria. Granulosis (GV) and nucleo-polyhedrosis viruses (NPV) may also be used as biological insecticides (e.g. Cydia pomonella granulovirus). ## Materials science and nanotechnology Current trends in nanotechnology promise to make much more versatile use of viruses. From the viewpoint of a materials scientist, viruses can be regarded as organic nanoparticles. Their surface carries specific tools designed to cross the barriers of their host cells. The size and shape of viruses, and the number and nature of the functional groups on their surface, is precisely defined. As such, viruses are commonly used in materials science as scaffolds for covalently linked surface modifications. A particular quality of viruses is that they can be tailored by directed evolution. The powerful techniques developed by life sciences are becoming the basis of engineering approaches towards nanomaterials, opening a wide range of applications far beyond biology and medicine. Because of their size, shape, and well-defined chemical structures, viruses have been used as templates for organizing materials on the nanoscale. Recent examples include work at the Naval Research Laboratory in Washington, DC, using Cowpea Mosaic Virus (CPMV) particles to amplify signals in microarray based sensors. In this application, the virus particles separate the fluorescent dyes used for signaling in order to prevent the formation of non-fluorescent dimers that act as quenchers. Another example is the use of CPMV as a nanoscale breadboard for molecular electronics. In April 2006, scientists at the Massachusetts Institute of Technology (MIT) created nanoscale metallic wires using a genetically-modified virus. The MIT team was able to use the virus to create a working battery with an energy density up to three times more than current materials. The potential exists for this technology to be used in liquid crystals, solar cells, fuel cells, and other electronics in the future. ## Weapons The ability of viruses to cause devastating epidemics in human societies has led to the concern that viruses could be weaponized for biological warfare. Further concern was raised by the successful recreation of the infamous 1918 influenza virus in a laboratory. The smallpox virus devastated numerous societies throughout history before its eradication. It currently exists in several secure laboratories in the world, and fears that it may be used as a weapon are not totally unfounded. The vaccine for smallpox is not safe, and during the years before the eradication of smallpox disease more people became seriously ill as a result of vaccination than did people from smallpox and smallpox vaccination is no longer universally practiced. Thus, the modern global human population has almost no established resistance to smallpox; if it were to be released, a massive loss of life could be sustained before the virus is brought under control. # Electron micrographs of viruses - Norovirus. This RNA virus causes winter vomiting disease. It is often in the news as a cause of gastro-enteritis on cruise ships and in hospitals. - Caliciviruses are related to Noroviruses. Caliciviruses are related to Noroviruses. - Torovirus. An enveloped RNA virus. Torovirus. An enveloped RNA virus. - Coronaviruses are a group of viruses that have a halo, or crown-like (corona) appearance when viewed under a microscope. Coronaviruses are a group of viruses that have a halo, or crown-like (corona) appearance when viewed under a microscope. - Ebola Virus is a filamentous RNA virus. - Measles virus. This is called a thin section where the virus particle has been cut in two. - Respiratory Syncytial Virus (RSV). In this preparation the ribonucleoprotein can be seen as a herring bone pattern. Respiratory Syncytial Virus (RSV). In this preparation the ribonucleoprotein can be seen as a herring bone pattern. - Parvovirus B19. Parvovirus B19 is a small DNA virus best known for causing a childhood exanthema called fifth disease or erythema infectiosum. - Human Papilloma Virus Human Papilloma Virus - Influenza virus - Transmission electron micrograph of Herpes virus an enveloped virus that looks like fried eggs by negative stain electron microscopy. Transmission electron micrograph of Herpes virus an enveloped virus that looks like fried eggs by negative stain electron microscopy. - TEM micrograph of Poliovirus virions.	Virus Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] A virus (from the Latin virus meaning "toxin" or "poison"), is a sub-microscopic infectious agent that is unable to grow or reproduce outside a host cell. Each viral particle, or virion, consists of genetic material, DNA or RNA, within a protective protein coat called a capsid. The capsid shape varies from simple helical and icosahedral (polyhedral or near-spherical) forms, to more complex structures with tails or an envelope. Viruses infect cellular life forms and are grouped into animal, plant and bacterial types, according to the type of host infected. Biologists debate whether or not viruses are living organisms. Some consider them non-living as they do not meet the criteria of the definition of life. For example, unlike most organisms, viruses do not have cells. However, viruses have genes and evolve by natural selection. Others have described them as organisms at the edge of life. Viral infections in human and animal hosts usually result in an immune response and disease. Often, a virus is completely eliminated by the immune system. Antibiotics have no effect on viruses, but antiviral drugs have been developed to treat life-threatening infections. Vaccines that produce lifelong immunity can prevent viral infections. # Etymology The word is from the Latin virus referring to poison and other noxious substances, first used in English in 1392.[1] Virulent, from Latin virulentus, "poisonous", dates to 1400.[2] A meaning of "agent that causes infectious disease" is first recorded in 1728,[1] before the discovery of viruses by the Russian-Ukrainian biologist Dmitry Ivanovsky in 1892. The adjective viral dates to 1948.[3] Today, virus is used to describe the biological viruses discussed above and as a metaphor for other parasitically-reproducing things, such as memes or computer viruses (since 1972).[2] The term virion is also used to refer to a single infective viral particle. The English plural form of virus is viruses. # Discovery of viruses Viral diseases such as rabies, yellow fever and smallpox have affected humans for centuries. There is hieroglyphical evidence of polio in ancient Egyptian medicine,[4] though the cause of this disease was unknown at the time. In the 10th century, Muhammad ibn Zakarīya Rāzi (Rhazes) wrote the Treatise on Smallpox and Measles, in which he gave the first clear descriptions of smallpox and measles.[5] In the 1020s, Avicenna wrote The Canon of Medicine, in which he discovered the contagious nature of infectious diseases, such as tuberculosis and sexually transmitted diseases, and their distribution through bodily contact or through water and soil;[6] stated that bodily secretion is contaminated by "foul foreign earthly bodies" before being infected;[7] and introduced the method of quarantine as a means of limiting the spread of contagious disease.[8] When the Black Death bubonic plague reached al-Andalus in the 14th century, Ibn Khatima discovered that infectious diseases are caused by microorganisms which enter the human body. The etiologic cause of the bubonic plague would later be identified as a bacterium. Another 14th century Andalusian physician, Ibn al-Khatib (1313-1374), wrote a treatise called On the Plague, in which he stated how infectious diseases can be transmitted through bodily contact and "through garments, vessels and earrings."[7] In 1717, Mary Montagu, the wife of an English ambassador to the Ottoman Empire, observed local women inoculating their children against smallpox.[9] In the late 18th century, Edward Jenner observed and studied Miss Sarah Nelmes, a milkmaid who had previously caught cowpox and was found to be immune to smallpox, a similar, but devastating virus. Jenner developed the smallpox vaccine based on these findings. After lengthy vaccination campaigns, the World Health Organization (WHO) certified the eradication of smallpox in 1979. In the late 19th century, Charles Chamberland developed a porcelain filter with pores small enough to remove cultured bacteria from their culture medium.[10] Dimitri Ivanovski used this filter to study an infection of tobacco plants, now known as tobacco mosaic virus. He passed crushed leaf extracts of infected tobacco plants through the filter, then used the filtered extracts to infect other plants, thereby proving that the infectious agent was not a bacterium. Similar experiments were performed by several other researchers, with similar results. These experiments showed that viruses are orders of magnitude smaller than bacteria. The term virus was coined by the Dutch microbiologist Martinus Beijerinck, who showed, using methods based on the work of Ivanovski, that tobacco mosaic disease is caused by something smaller than a bacterium. He coined the Latin phrase "contagium vivum fluidum" (which means "soluble living germ") as the first idea of the virus.[11] The first human virus identified was Yellow Fever virus. In the early 20th century, Frederick Twort discovered that bacteria could be infected by viruses.[12] Felix d'Herelle, working independently, showed that a preparation of viruses caused areas of cellular death on thin cell cultures spread on agar. Counting the dead areas allowed him to estimate the original number of viruses in the suspension. The invention of electron microscopy provided the first look at viruses. In 1935, Wendell Stanley crystallized the tobacco mosaic virus and found it to be mostly protein.[13] A short time later, the virus was separated into protein and nucleic acid parts.[14][15] In 1939, Max Delbrück and E.L. Ellis demonstrated that, in contrast to cellular organisms, bacteriophage reproduce in "one step", rather than exponentially.[16] A major problem for early virologists was the inability to propagate viruses on sterile culture media, as is done with cellular microorganisms. This limitation required medical virologists to infect living animals with infectious material, which is dangerous. The first breakthrough came in 1931, when Ernest William Goodpasture demonstrated the growth of influenza and several other viruses in fertile chicken eggs.[17] However, some viruses would not grow in chicken eggs, and a more flexible technique was needed for propagation of viruses. The solution came in 1949 when John Franklin Enders, Thomas H. Weller and Frederick Chapman Robbins together developed a technique to grow the polio virus in cultures of living animal cells.[18] Their methods have since been extended and applied to the growth of viruses and other infectious agents that do not grow on sterile culture media. # Origins The origin of modern viruses is not entirely clear. It may be that no single mechanism can account for their origin.[19] They do not fossilize well, so molecular techniques have been the most useful means of hypothesising how they arose.[20] Research in microfossil identification and molecular biology may yet discern fossil evidence dating to the Archean or Proterozoic eons. Two main hypotheses currently exist.[21] Small viruses with only a few genes may be runaway stretches of nucleic acid originating from the genome of a living organism. Their genetic material could have been derived from transferable genetic elements such as plasmids or transposons, that are prone to moving within, leaving, and entering genomes. New viruses are emerging de novo and therefore, it is not always the case that viruses have "ancestors".[22] Viruses with larger genomes, such as poxviruses, may have once been small cells that parasitized larger host cells. Over time, genes not required by their parasitic lifestyle would have been lost in a streamlining process known as "retrograde-evolution" or "reverse-evolution". The bacteria Rickettsia and Chlamydia are living cells that, like viruses, can only reproduce inside host cells. They lend credence to the streamlining hypothesis, as their parasitic lifestyle is likely to have caused the loss of genes that enabled them to survive outside a host cell. It is possible that viruses represent a primitive form of self replicating DNA and are a precursor to life as it is currently defined.[23] Other infectious particles which are even simpler in structure than viruses include viroids, satellites, and prions. # Classification In taxonomy, the classification of viruses is difficult owing to the lack of a fossil record and the dispute over whether they are living or non-living.[24][25] They do not fit easily into any of the domains of biological classification, and classification begins at the family rank. However, the domain name of Acytota (without cells) has been suggested. This would place viruses on a par with the other domains of Eubacteria, Archaea, and Eukarya. Not all families are currently classified into orders, nor all genera classified into families. In 1962, André Lwoff, Robert Horne, and Paul Tournier were the first to develop a means of virus classification, based on the Linnaean hierarchical system.[26] This system based classification on phylum, class, order, family, genus, and species. Viruses were grouped according to their shared properties (not of their hosts) and the type of nucleic acid forming their genomes.[27] Following this initial system, a few modifications were made and the International Committee on Taxonomy of Viruses was developed (ICTV). ### ICTV classification The International Committee on Taxonomy of Viruses (ICTV) developed the current classification system and put in place guidelines that put a greater weighting on certain virus properties to maintain family uniformity. A universal system for classifying viruses, and a unified taxonomy, has been established since 1966. In determining order, taxonomists should consider the type of nucleic acid present, whether the nucleic acid is single- or double-stranded, and the presence or absence of an envelope. After these three main properties, other characteristics can be considered: the type of host, the capsid shape, immunological properties and the type of disease it causes. The system makes use of a series of ranked taxons. The general structure is as follows: The recognition of orders is very recent; to date, only three have been named, and most families remain unplaced. The committee does not formally distinguish between subspecies, strains, and isolates. In total there are three orders, 56 families, nine subfamilies, and 233 genera. ICTV recognizes about 1,550 virus species, but about 30,000 virus strains and isolates are being tracked by virologists.[28] The Nobel Prize-winning biologist David Baltimore devised the Baltimore classification system.[29][30] The ICTV classification system is used in conjunction with the Baltimore classification system in modern virus classification.[31][32][33] ### Baltimore Classification The Baltimore classification of viruses is based on the mechanism of mRNA production. Viruses must generate positive strand mRNAs from their genomes to produce proteins and replicate themselves, but different mechanisms are used to achieve this in each virus family. This classification places viruses into seven groups: Template:Baltimore groups As an example of viral classification, the chicken pox virus, Varicella zoster (VZV), belongs to family Herpesviridae, subfamily Alphaherpesvirinae and genus Varicellovirus. It remains unranked in terms of order. VZV is in Group I of the Baltimore Classification because it is a dsDNA virus that does not use reverse transcriptase. # Structure A complete virus particle, known as a virion, consists of nucleic acid surrounded by a protective coat of protein called a capsid. Viruses can have a lipid "envelope" derived from the host cell membrane. A capsid is made from proteins encoded by the viral genome and its shape serves as the basis for morphological and antigenic distinction.[34][35] Virally coded protein subunits will self-assemble to form a capsid, generally requiring the presence of the virus genome. However, complex viruses code for proteins which assist in the construction of their capsid.[21] Proteins associated with nucleic acid are known as nucleoproteins, and the association of viral capsid proteins with viral nucleic acid is called a nucleocapsid. In general, there are four main morphological virus types: ## Electron microscopy Electron microscopy is the most common method used to study the morphology of viruses. To increase the contrast between viruses and the background, electron-dense "stains" are used. These are solutions of salts of heavy metals such as tungsten, that scatter the electrons from regions covered with the stain. When virus particles are coated with stain (positive staining), fine detail is obscured. Negative staining overcomes this problem by staining the background only.[38] ## Size A medium-sized virion next to a flea is roughly equivalent to a human next to a mountain twice the size of Mount Everest. Some filoviruses have a total length of up to 1400 nm, however their capsid diameters are only about 80 nm. Most viruses which have been studied have a capsid diameter between 10 and 300 nanometres. Most viruses are unable to be seen with a light microscope but some are as large or larger than the smallest bacteria and can be seen under high optical magnification. More commonly, both scanning and transmission electron microscopes are used to visualize virus particles. # Genome An enormous variety of genomic structures can be seen among viral species; as a group they contain more structural genomic diversity than the entire kingdoms of either plants, animals, or bacteria.[39] ## Nucleic acid A virus may employ either DNA or RNA as the nucleic acid. Rarely do they contain both, however cytomegalovirus is an exception to this, possessing a DNA core with several mRNA segments.[21] By far most viruses have RNA. Plant viruses tend to have single-stranded RNA and bacteriophages tend to have double-stranded DNA.[21] Some virus species possess abnormal nucleotides, such as hydroxymethylcytosine instead of cytosine, as a normal part of their genome.[21] ## Shape Viral genomes may be circular, such as polyomaviruses, or linear, such as adenoviruses. The type of nucleic acid is irrelevant to the shape of the genome. Among RNA viruses, the genome is often divided up into separate parts within the virion and are called segmented. Double-stranded RNA genomes and some single-stranded RNA genomes are segmented.[21] Each segment often codes for one protein and they are usually found together in one capsid. Every segment is not required to be in the same virion for the overall virus to be infectious, as demonstrated by the brome mosaic virus.[21] ## Strandedness A viral genome, irrespective of nucleic acid type, may be either single-stranded or double-stranded. Single-stranded genomes consist of an unpaired nucleic acid, analogous to one-half of a ladder split down the middle. Double-stranded genomes consist of 2 complementary paired nucleic acids, analogous to a ladder. Viruses, such as those belonging to the Hepadnaviridae, contain a genome which is partially double-stranded and partially single-stranded.[39] Viruses that infect humans include double-stranded RNA (e.g. Rotavirus), single-stranded RNA (e.g. Influenza virus), single-stranded DNA (e.g. Parvovirus B19) and double-stranded DNA (Herpes virus). ## Sense For viruses with RNA as their nucleic acid, the strands are said to be either positive-sense (called the plus-strand) or negative-sense (called the minus-strand), depending on whether it is complementary to viral mRNA. Positive-sense viral RNA is identical to viral mRNA and thus can be immediately translated by the host cell. Negative-sense viral RNA is complementary to mRNA and thus must be converted to positive-sense RNA by an RNA polymerase before translation. DNA nomenclature is similar to RNA nomenclature, in that the coding strand for the viral mRNA is complementary to it (-), and the non-coding strand is a copy of it (+). ## Genome size Genome size in terms of the weight of nucleotides varies between species. The smallest genomes code for only four proteins and weigh about 106 Daltons, the largest weigh about 108 Daltons and code for over one hundred proteins.[21] RNA viruses generally have smaller genome sizes than DNA viruses due to a higher error-rate when replicating, resulting in a maximum upper size limit. Beyond this limit, errors in the genome when replicating render the virus useless or uncompetitive. To compensate for this, RNA viruses often have segmented genomes where the genome is split into smaller molecules, thus reducing the chance of error.[40] In contrast, DNA viruses generally have larger genomes due to the high fidelity of their replication enzymes.[39] ## Gene reassortment There is an evolutionary advantage in having a segmented genome. Different strains of a virus with a segmented genome, from a pig or a bird or a human for example, such as Influenza virus, can shuffle and combine with other genes producing progeny viruses or (offspring) that have unique characteristics. This is called reassortment or viral sex.[41] This is one reason why Influenza virus constantly changes.[42] ## Genetic recombination Genetic recombination is the process by which a strand of DNA is broken and then joined to the end of a different DNA molecule. This can occur when viruses infect cells simultaneously and studies of viral evolution have shown that recombination has been rampant in the species studied.[43] Recombination is common to both RNA and DNA viruses.[44][45] ## Genetic change Viruses undergo genetic change by several mechanisms. These include a process called genetic drift where individual bases in the DNA or RNA mutate to other bases. Most of these point mutations are silent in that they do not change the protein that the gene encodes, but others can confer evolutionary advantages such as resistance to antiviral drugs.[46] Antigenic shift is where there is a major change in the genome of the virus. This occurs as a result of recombination or reassortment (see above). When this happens with influenza viruses, pandemics may result.[47][48] By genome rearrangement the structure of the gene changes although no mutations have necessarily occurred.[49] RNA viruses are much more likely to mutate than DNA viruses for the reasons outlined above. Viruses often exist as quasispecies or swarms of viruses of the same species but with slightly different genome nucleoside sequences. Such quasispecies are a prime target for natural selection.[50] # Replication Viral populations do not grow through cell division, because they are acellular; instead, they use the machinery and metabolism of a host cell to produce multiple copies of themselves. A virus can still cause degenerative effects within a cell without causing its death; collectively these are termed cytopathic effects. ## Virus life cycle The life cycle of viruses differs greatly between species (see below) but there are six basic stages in the life cycle of viruses: - Attachment is a specific binding between viral capsid proteins and specific receptors on the host cellular surface. This specificity determines the host range of a virus. For example, the human immunodeficiency virus (HIV) infects only human T cells, because its surface protein, gp120, can interact with CD4 and receptors on the T cell's surface. This mechanism has evolved to favour those viruses that only infect cells that they are capable of replicating in. Attachment to the receptor can induce the viral-envelope protein to undergo changes that results in the fusion of viral and cellular membranes. - Penetration: following attachment, viruses enter the host cell through receptor mediated endocytosis or membrane fusion. - Uncoating is a process in which the viral capsid is degraded by viral enzymes or host enzymes thus releasing the viral genomic nucleic acid. - Replication involves synthesis of viral messenger RNA (mRNA) for viruses except positive sense RNA viruses (see above), viral protein synthesis and assembly of viral proteins and viral genome replication. - Following the assembly of the virus particles post-translational modification of the viral proteins often occurs. In viruses such as HIV, this modification, (sometimes called maturation), occurs after the virus has been released from the host cell.[51] - Viruses are released from the host cell by lysis (see below). Enveloped viruses (e.g., HIV) typically are released from the host cell by budding. During this process, the virus acquires its phospholipid envelope which contains embedded viral glycoproteins. ### DNA viruses Animal DNA viruses, such as herpesviruses, enter the host via endocytosis, the process by which cells take in material from the external environment. Frequently after a chance collision with an appropriate surface receptor on a cell, the virus penetrates the cell, the viral genome is released from the capsid, and host polymerases begin transcribing viral mRNA. New virions are assembled and released either by cell lysis or by budding off the cell membrane. ### RNA viruses Animal RNA viruses can be placed into about four different groups depending on their modes of replication. The polarity of the RNA largely determines the replicative mechanism, as well as whether the genetic material is single-stranded or double-stranded. Some RNA viruses are actually DNA-based but use an RNA-intermediate to replicate. RNA viruses are dependent on virally encoded RNA replicase to create copies of their genomes. ### Reverse transcribing viruses Reverse transcribing viruses replicate using reverse transcription, which is the formation of DNA from an RNA template. Reverse transcribing viruses containing RNA genomes use a DNA intermediate to replicate, whereas those containing DNA genomes use an RNA intermediate during genome replication. Both types use the reverse transcriptase enzyme to carry out the nucleic acid conversion. Both types are susceptible to antiviral drugs that inhibit the reverse transcriptase enzyme, e.g. zidovudine and lamivudine. An example of the first type is HIV which is a retrovirus. Retroviruses often integrate the DNA produced by reverse transcription into the host genome. This is why HIV infection can at present, only be treated and not cured. Examples of the second type are the Hepadnaviridae, which includes the Hepatitis B virus and the Caulimoviridae - e.g. Cauliflower mosaic virus. ### Bacteriophages Bacteriophages infect specific bacteria by binding to surface receptor molecules and then enter the cell. Within a short amount of time, in some cases, just minutes, bacterial polymerase starts translating viral mRNA into protein. These proteins go on to become either new virions within the cell, helper proteins which help assembly of new virions, or proteins involved in cell lysis. Viral enzymes aid in the breakdown of the cell membrane, and in the case of the T4 phage, in just over twenty minutes after injection over three hundred phages could be released. # Lifeform debate Viruses have been described as "organisms at the edge of life",[52] but argument continues over whether viruses are truly alive. According to the United States Code they are considered microorganisms in the sense of biological weaponry and malicious use. Scientists, however, are divided. Things become more complicated as they look at viroids and prions. Viruses resemble other organisms in that they possess genes and can evolve in infected cells by natural selection.[53][54] They can reproduce by creating multiple copies of themselves through self-assembly. Viruses do not have a cell structure (regarded as the basic unit of life), although they do have genes. Additionally, although they reproduce, they do not self-metabolize and require a host cell to replicate and synthesize new products. However, bacterial species such as Rickettsia and Chlamydia are considered living organisms but are unable to reproduce outside a host cell. An argument can be made that accepted forms of life use cell division to reproduce, whereas viruses spontaneously assemble within cells. The comparison is drawn between viral self-assembly and the autonomous growth of non-living crystals. Virus self-assembly within host cells has implications for the study of the origin of life, as it lends credence to the hypothesis that life could have started as self-assembling organic molecules.[55] If viruses are considered alive, then the criteria specifying life will have to exclude the cell. If viruses are said to be alive, the question could follow of whether even smaller infectious particles, such as viroids and prions, are alive. # Viruses and disease Examples of common human diseases caused by viruses include the common cold, the flu, chickenpox and cold sores. Serious diseases such as Ebola, AIDS, avian influenza and SARS are caused by viruses. The relative ability of viruses to cause disease is described in terms of virulence. Other diseases are under investigation as to whether they too have a virus as the causative agent, such as the possible connection between Human Herpesvirus Six (HHV6) and neurological diseases such as multiple sclerosis and chronic fatigue syndrome. There is current controversy over whether the borna virus, previously thought of as causing neurological diseases in horses, could be responsible for psychiatric illnesses in humans.[56] Viruses have different mechanisms by which they produce disease in an organism, which largely depends on the species. Mechanisms at the cellular level primarily include cell lysis, the breaking open and subsequent death of the cell. In multicellular organisms, if enough cells die the whole organism will start to suffer the effects. Although viruses cause disruption of healthy homeostasis, resulting in disease, they may exist relatively harmlessly within an organism. An example would include the ability of the herpes simplex virus, which cause cold sores, to remain in a dormant state within the human body. This is called latency[57] and is a characteristic of the herpes viruses including the Epstein-Barr virus, which causes glandular fever, and the Varicella zoster virus, which causes chicken pox. Latent chickenpox infections return in later life as the disease called shingles. Some viruses can cause life-long or chronic infections, where the viruses continue to replicate in the body despite the hosts' defense mechanisms.[58] This is common in Hepatitis B virus and Hepatitis C Virus infections. People chronically infected with the Hepatitis B virus are known as carriers who serve as reservoirs of infectious virus. In some populations, with a high proportion of carriers, the disease is said to be endemic.[59] When diagnosing Hepatitis B virus infections, it is important to distinguish between acute and chronic infections.[60] ## Epidemiology Viral epidemiology is the branch of medical science dealing with the transmission and control of virus infections in humans. Transmission of viruses can be vertical, that is from mother to child, or horizontal, which means from person to person. Examples of vertical transmission include Hepatitis B virus and HIV where the baby is born already infected with the virus.[61] Another, more rare, example is the Varicella zoster virus, which although causing relatively mild infections in humans, can be fatal to the foetus and newly born baby.[62] Horizontal transmission is the most common mechanism of spread of viruses in populations. Transmission can be exchange of blood by sexual activity, e.g. HIV, Hepatitis B and Hepatitis C; by mouth by exchange of saliva, e.g. Epstein-Barr virus, or from contaminated food or water, e.g. Norovirus; by breathing in viruses in the form of aerosols, e.g. Influenza virus; and by insect vectors such as mosquitoes, e.g. dengue. The rate or speed of transmission of viral infections depends on factors that include population density, the number of susceptible individuals, (i.e. those who are not immune),[63] the quality of health care and the weather.[64] ## Epidemics and pandemics Native American populations were devastated by contagious diseases, particularly smallpox, brought to the Americas by European colonists. It is unclear how many Native Americans were killed by foreign diseases after the arrival of Columbus in the Americas, but the numbers have been estimated to be close to 70% of the indigenous population. The damage done by this disease significantly aided European attempts to displace and conquer the native population.[65][66][67][68][69][70][71] A pandemic is a world-wide epidemic. The 1918 flu pandemic, commonly referred to as the Spanish flu, was a category 5 influenza pandemic caused by an unusually severe and deadly Influenza A virus. The victims were often healthy young adults, in contrast to most influenza outbreaks which predominantly affect juvenile, elderly, or otherwise weakened patients. The Spanish flu pandemic lasted from 1918 to 1919. Older estimates say it killed 40–50 million people,[72] while more recent research suggests that it may have killed as many as 100 million people, or 5% of the world's population in 1918.[73] Most researchers believe that HIV originated in sub-Saharan Africa during the twentieth century;[74] it is now a pandemic, with an estimated 38.6 million people now living with the disease worldwide.[75] As of January 2006, the Joint United Nations Programme on HIV/AIDS (UNAIDS) and the World Health Organization (WHO) estimate that AIDS has killed more than 25 million people since it was first recognized on June 5, 1981, making it one of the most destructive epidemics in recorded history.[76] Several highly lethal viral pathogens are members of the Filoviridae. Filoviruses are filament-like viruses that cause viral hemorrhagic fever, and include the Ebola and Marburg viruses. The Marburg virus attracted widespread press attention in April 2005 for an outbreak in Angola. Beginning in October 2004 and continuing into 2005, the outbreak was the world's worst epidemic of any kind of viral hemorrhagic fever.[77] ## Viruses and cancer Viruses are an established cause of malignancy in humans and other species. The main viruses associated with human cancers are human papillomavirus, hepatitis B and hepatitis C virus, Epstein-Barr virus, and human T-lymphotropic virus. Hepatitis viruses, including hepatitis B and hepatitis C, can induce a chronic viral infection that leads to liver cancer.[78][79] Infection by human T-lymphotropic virus can lead to tropical spastic paraparesis and adult T-cell leukemia.[80] Human papillomaviruses are an established cause of cancers of cervix, skin, anus, and penis.[81] Within the Herpesviridae, Kaposi's sarcoma-associated herpesvirus causes Kaposi's sarcoma and body cavity lymphoma, and Epstein–Barr virus causes Burkitt's lymphoma, Hodgkin’s lymphoma, B lymphoproliferative disorder and nasopharyngeal carcinoma.[82] ## Laboratory diagnosis In the diagnostic laboratory, virus infections are confirmed by several methods that include: - Growth of the virus in a cell culture from a specimen taken from the patient. - Detection of virus-specific IgM antibody (see below) in the blood. - Detection of virus antigens by ELISA in tissues and fluids. - Detection of virus encoded DNA and RNA by PCR. - Observation of virus particles by electron microscopy. ## Prevention and treatment Because viruses use the machinery of a host cell to reproduce and reside within them, they are difficult to eliminate without killing the host cell. The most effective medical approaches to viral diseases so far are vaccinations to provide resistance to infection, and antiviral drugs which treat the symptoms of viral infections. ## Host immune response The body's first line of defense against viruses is the innate immune system. This comprises cells and other mechanisms that defend the host from infection in a non-specific manner. This means that the cells of the innate system recognize, and respond to, pathogens in a generic way, but unlike the adaptive immune system, it does not confer long-lasting or protective immunity to the host.[83] RNA interference is an important innate defense against viruses.[84] Many viruses have a replication strategy that involves double-stranded RNA dsRNA. When such a virus infects a cell, it releases its RNA molecule or molecules, which immediately bind to a protein complex called Dicer that cuts the RNA into smaller pieces. A biochemical pathway called the RISC complex is activated which degrades the viral mRNA and the cell survives the infection. Rotaviruses avoid this mechanism by not uncoating fully inside the cell and by releasing newly produced mRNA through pores in the particle's inner capsid. The genomic dsRNA remains protected inside the core of the virion.[85][86] When the adaptive immune system of a vertebrate encounters a virus, it produces specific antibodies which bind to the virus and render it non-infectious. This is called humoral immunity. Two types of antibodies are important. The first called IgM is highly effective at neutralizing viruses but is only produced by the cells of the immune system for a few weeks. The second, called, IgG is produced indefinitely. The presence of IgM in the blood of the host is used to test for acute infection, whereas IgG indicates an infection sometime in the past.[87] Both types of antibodies are measured when tests for immunity are carried out.[88] A second defense of vertebrates against viruses is called cell-mediated immunity and involves immune cells known as T cells. The body's cells constantly display short fragments of their proteins on the cell's surface, and if a T cell recognizes a suspicious viral fragment there, the host cell is destroyed by T killer cells and the virus-specific T-cells proliferate. Cells such as the macrophage are specialists at this antigen presentation.[89][90] Not all virus infections produce a protective immune response in this way. HIV evades the immune system by constantly changing the amino acid sequence of the proteins on the surface of the virion. These persistent viruses evade immune control by sequestration, blockade of antigen presentation, cytokine resistance, evasion of natural killer cell activities, escape from apoptosis, and antigenic shift.[91] Other viruses, called "neurotropic viruses", are disseminated by neural spread where the immune system may be unable to reach them. The production of interferon is an important host defense mechanism.[92] ## Vaccines Vaccination is a cheap and effective way of preventing infections by viruses. Vaccines were used to prevent viral infections long before the discovery of the actual viruses. Their use has resulted in a dramatic decline in morbidity (illness) and mortality (death) associated with viral infections such as polio, measles, mumps and rubella.[93] Smallpox infections have been eradicated.[94] Currently vaccines are available to prevent over thirteen viral infections of humans,[95] and more are used to prevent viral infections of animals.[96] Vaccines can consist of live-attenuated or killed viruses, or viral proteins (antigens).[97] Live vaccines contain weakened forms of the virus that causes the disease. Such viruses are called attenuated. Live vaccines can be dangerous when given to people with a weak immunity, (who are described as immunocompromised), because in these people, the weakened virus can cause the original disease.[98] Biotechnology and genetic engineering techniques are used to produce subunit vaccines. These vaccines use only the capsid proteins of the virus. Hepatitis B vaccine is an example of this type of vaccine.[99] Subunit vaccines are safe for immunocompromised patients because they cannot cause the disease.[100] The Yellow Fever virus vaccine, a live-attenuated strain called 17D, is arguably the safest and most effective vaccine ever generated. ## Antiviral drugs Over the past twenty years, the development of antiviral drugs has increased rapidly. This has been driven by the AIDS epidemic. Antiviral drugs are often nucleoside analogues, (fake DNA building blocks), which viruses incorporate into their genomes during replication. The life-cycle of the virus is then halted because the newly synthesized DNA is inactive. This is because these analogues lack the hydroxyl groups which along with phosphorus atoms, link together to form the strong "backbone" of the DNA molecule. This is called DNA chain termination.[101] Examples of nucleoside analogues are aciclovir for Herpes virus infections and lamivudine for HIV and Hepatitis B virus infections. Aciclovir is one of the oldest and most frequently prescribed antiviral drugs.[102] Other antiviral drugs in use target different stages of the viral life cycle. HIV is dependent on a proteolytic enzyme called the HIV-1 protease for it to become fully infectious. There is a class of drugs called protease inhibitors which have been designed to inactivate the enzyme. Hepatitis C is caused by an RNA virus. In 80% of people infected, the disease is chronic, and without treatment, they are infected and infectious for the remainder of their lives. However, there is now an effective treatment using the nucleoside analogue drug ribavirin combined with interferon.[103] The treatment of chronic carriers of the Hepatitis B virus by using a similar strategy using lamivudine is being developed.[104] ## Notable examples The clinically most notable[105] virus species belong to the following families: - Adenoviridae - Picornaviridae - Herpesviridae - Hepadnaviridae - Flaviviridae - Retroviridae - Orthomyxoviridae - Paramyxoviridae - Papovaviridae - Rhabdoviridae - Reoviridae - Togaviridae # Applications ## Life sciences and medicine Viruses are important to the study of molecular and cellular biology as they provide simple systems that can be used to manipulate and investigate the functions of cells. The study and use of viruses have provided valuable information about aspects of cell biology. For example, viruses have been useful in the study of genetics and helped our understanding of the basic mechanisms of molecular genetics, such as DNA replication, transcription, RNA processing, translation, protein transport, and immunology. Geneticists often use viruses as vectors to introduce genes into cells that they are studying. This is useful for making the cell produce a foreign substance, or to study the effect of introducing a new gene into the genome. In similar fashion, virotherapy uses viruses as vectors to treat various diseases, as they can specifically target cells and DNA. It shows promising use in the treatment of cancer and in gene therapy. Eastern European scientists have used phage therapy as an alternative to antibiotics for some time, and interest in this approach is increasing, due to the high level of antibiotic resistance now found in some pathogenic bacteria.[108] Granulosis (GV) and nucleo-polyhedrosis viruses (NPV) may also be used as biological insecticides (e.g. Cydia pomonella granulovirus). ## Materials science and nanotechnology Current trends in nanotechnology promise to make much more versatile use of viruses. From the viewpoint of a materials scientist, viruses can be regarded as organic nanoparticles.[109] Their surface carries specific tools designed to cross the barriers of their host cells. The size and shape of viruses, and the number and nature of the functional groups on their surface, is precisely defined. As such, viruses are commonly used in materials science as scaffolds for covalently linked surface modifications. A particular quality of viruses is that they can be tailored by directed evolution. The powerful techniques developed by life sciences are becoming the basis of engineering approaches towards nanomaterials, opening a wide range of applications far beyond biology and medicine.[110] Because of their size, shape, and well-defined chemical structures, viruses have been used as templates for organizing materials on the nanoscale. Recent examples include work at the Naval Research Laboratory in Washington, DC, using Cowpea Mosaic Virus (CPMV) particles to amplify signals in microarray based sensors. In this application, the virus particles separate the fluorescent dyes used for signaling in order to prevent the formation of non-fluorescent dimers that act as quenchers.[111] Another example is the use of CPMV as a nanoscale breadboard for molecular electronics.[112] In April 2006, scientists at the Massachusetts Institute of Technology (MIT) created nanoscale metallic wires using a genetically-modified virus.[113] The MIT team was able to use the virus to create a working battery with an energy density up to three times more than current materials. The potential exists for this technology to be used in liquid crystals, solar cells, fuel cells, and other electronics in the future. ## Weapons The ability of viruses to cause devastating epidemics in human societies has led to the concern that viruses could be weaponized for biological warfare. Further concern was raised by the successful recreation of the infamous 1918 influenza virus in a laboratory.[114] The smallpox virus devastated numerous societies throughout history before its eradication. It currently exists in several secure laboratories in the world, and fears that it may be used as a weapon are not totally unfounded. The vaccine for smallpox is not safe, and during the years before the eradication of smallpox disease more people became seriously ill as a result of vaccination than did people from smallpox[115] and smallpox vaccination is no longer universally practiced.[116] Thus, the modern global human population has almost no established resistance to smallpox; if it were to be released, a massive loss of life could be sustained before the virus is brought under control. # Electron micrographs of viruses - Norovirus. This RNA virus causes winter vomiting disease. It is often in the news as a cause of gastro-enteritis on cruise ships and in hospitals. - Caliciviruses are related to Noroviruses. Caliciviruses are related to Noroviruses. - Torovirus. An enveloped RNA virus. Torovirus. An enveloped RNA virus. - Coronaviruses are a group of viruses that have a halo, or crown-like (corona) appearance when viewed under a microscope. Coronaviruses are a group of viruses that have a halo, or crown-like (corona) appearance when viewed under a microscope. - Ebola Virus is a filamentous RNA virus. - Measles virus. This is called a thin section where the virus particle has been cut in two. - Respiratory Syncytial Virus (RSV). In this preparation the ribonucleoprotein can be seen as a herring bone pattern. Respiratory Syncytial Virus (RSV). In this preparation the ribonucleoprotein can be seen as a herring bone pattern. - Parvovirus B19. Parvovirus B19 is a small DNA virus best known for causing a childhood exanthema called fifth disease or erythema infectiosum. - Human Papilloma Virus Human Papilloma Virus - Influenza virus - Transmission electron micrograph of Herpes virus an enveloped virus that looks like fried eggs by negative stain electron microscopy. Transmission electron micrograph of Herpes virus an enveloped virus that looks like fried eggs by negative stain electron microscopy. - TEM micrograph of Poliovirus virions.	https://www.wikidoc.org/index.php/Tumor_virus
a648de509e3e94debf596ef298a68300e772d537	wikidoc	U2AF2	U2AF2 Splicing factor U2AF 65 kDa subunit is a protein that in humans is encoded by the U2AF2 gene. # Function U2 auxiliary factor (U2AF), composed of a large and a small subunit, is a non-snRNP protein required for the binding of U2 snRNP to the pre-mRNA branch site. This gene encodes the U2AF large subunit, which contains a sequence-specific RNA-binding region with 3 RNA recognition motifs and an Arg/Ser-rich domain necessary for splicing. The large subunit binds to the polypyrimidine tract of introns early during spliceosome assembly. Multiple alternatively spliced transcript variants have been detected for this gene, but the full-length natures of only two have been determined to date. In humans and other tetrapods, it has been shown that without U2AF2, the splicing process is inhibited. However, in zebrafish and other teleosts the RNA splicing process can still occur on certain genes in the absence of U2AF2. This may be because 10% of genes have alternating TG and AC base pairs at the 3' splice site (3'ss) and 5' splice site (5'ss) respectively on each intron, which alters the secondary structure of the RNA and influences splicing. # Interactions U2AF2 has been shown to interact with: - PUF60, - SF1, - SFRS11, - SFRS2IP, - SRPK2, - U2 small nuclear RNA auxiliary factor 1 and - WT1.	U2AF2 Splicing factor U2AF 65 kDa subunit is a protein that in humans is encoded by the U2AF2 gene.[1] # Function U2 auxiliary factor (U2AF), composed of a large and a small subunit, is a non-snRNP protein required for the binding of U2 snRNP to the pre-mRNA branch site. This gene encodes the U2AF large subunit, which contains a sequence-specific RNA-binding region with 3 RNA recognition motifs and an Arg/Ser-rich domain necessary for splicing. The large subunit binds to the polypyrimidine tract of introns early during spliceosome assembly. Multiple alternatively spliced transcript variants have been detected for this gene, but the full-length natures of only two have been determined to date.[2] In humans and other tetrapods, it has been shown that without U2AF2, the splicing process is inhibited. However, in zebrafish and other teleosts the RNA splicing process can still occur on certain genes in the absence of U2AF2. This may be because 10% of genes have alternating TG and AC base pairs at the 3' splice site (3'ss) and 5' splice site (5'ss) respectively on each intron, which alters the secondary structure of the RNA and influences splicing.[3] # Interactions U2AF2 has been shown to interact with: - PUF60,[4][5] - SF1,[4][6][7] - SFRS11,[8] - SFRS2IP,[9] - SRPK2,[4][10] - U2 small nuclear RNA auxiliary factor 1[4][11] and - WT1.[12]	https://www.wikidoc.org/index.php/U2AF2
a31f09d0577990126e2e6914689c6dfb34dc9203	wikidoc	UBAP1	UBAP1 Ubiquitin-associated protein 1 is a protein that in humans is encoded by the UBAP1 gene. This gene is a member of the UBA domain family, whose members include proteins having connections to ubiquitin and the ubiquitination pathway. The ubiquitin associated domain is thought to be a non-covalent ubiquitin binding domain consisting of a compact three helix bundle. This particular protein originates from a gene locus in a refined region on chromosome 9 undergoing loss of heterozygosity in nasopharyngeal carcinoma (NPC). Taking into account its cytogenetic location, this UBA domain family member is being studies as a putative target for mutation in nasopharyngeal carcinomas. # Model organisms Model organisms have been used in the study of UBAP1 function. A conditional knockout mouse line, called Ubap1tm1a(EUCOMM)Wtsi was generated as part of the International Knockout Mouse Consortium program — a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists — at the Wellcome Trust Sanger Institute. Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion. Twenty five tests were carried out and two phenotypes were reported. Fewer homozygous mutant embryos were identified during gestation than predicted, and none survived until weaning. The remaining tests were carried out on heterozygous mutant adult mice; no significant abnormalities were observed in these animals.	UBAP1 Ubiquitin-associated protein 1 is a protein that in humans is encoded by the UBAP1 gene.[1] This gene is a member of the UBA domain family, whose members include proteins having connections to ubiquitin and the ubiquitination pathway. The ubiquitin associated domain is thought to be a non-covalent ubiquitin binding domain consisting of a compact three helix bundle. This particular protein originates from a gene locus in a refined region on chromosome 9 undergoing loss of heterozygosity in nasopharyngeal carcinoma (NPC). Taking into account its cytogenetic location, this UBA domain family member is being studies as a putative target for mutation in nasopharyngeal carcinomas.[1] # Model organisms Model organisms have been used in the study of UBAP1 function. A conditional knockout mouse line, called Ubap1tm1a(EUCOMM)Wtsi[6][7] was generated as part of the International Knockout Mouse Consortium program — a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists — at the Wellcome Trust Sanger Institute.[8][9][10] Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion.[4][11] Twenty five tests were carried out and two phenotypes were reported. Fewer homozygous mutant embryos were identified during gestation than predicted, and none survived until weaning. The remaining tests were carried out on heterozygous mutant adult mice; no significant abnormalities were observed in these animals.[4]	https://www.wikidoc.org/index.php/UBAP1
fdb8458fb46b54c86aa2bfc455e33682a44c7840	wikidoc	UBE1C	UBE1C NEDD8-activating enzyme E1 catalytic subunit is a protein that in humans is encoded by the UBA3 gene. The modification of proteins with ubiquitin is an important cellular mechanism for targeting abnormal or short-lived proteins for degradation. Ubiquitination involves at least three classes of enzymes: ubiquitin-activating enzymes, or E1s, ubiquitin-conjugating enzymes, or E2s, and ubiquitin-protein ligases, or E3s. This gene encodes a member of the E1 ubiquitin-activating enzyme family. The encoded enzyme associates with AppBp1, an amyloid beta precursor protein binding protein, to form a heterodimer, and then the enzyme complex activates NEDD8, a ubiquitin-like protein, which regulates cell division, signaling and embryogenesis. Multiple alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. This enzyme contains an E2 binding domain, which resembles ubiquitin, and recruits the catalytic core of the E2 enzyme UBE2M (Ubc12) in a similar manner to that in which ubiquitin interacts with ubiquitin binding domains. # Interactions UBE1C has been shown to interact with NEDD8, APPBP1 and UBE2M.	UBE1C NEDD8-activating enzyme E1 catalytic subunit is a protein that in humans is encoded by the UBA3 gene.[1][2] The modification of proteins with ubiquitin is an important cellular mechanism for targeting abnormal or short-lived proteins for degradation. Ubiquitination involves at least three classes of enzymes: ubiquitin-activating enzymes, or E1s, ubiquitin-conjugating enzymes, or E2s, and ubiquitin-protein ligases, or E3s. This gene encodes a member of the E1 ubiquitin-activating enzyme family. The encoded enzyme associates with AppBp1, an amyloid beta precursor protein binding protein, to form a heterodimer, and then the enzyme complex activates NEDD8, a ubiquitin-like protein, which regulates cell division, signaling and embryogenesis. Multiple alternatively spliced transcript variants encoding distinct isoforms have been found for this gene.[2] This enzyme contains an E2 binding domain, which resembles ubiquitin, and recruits the catalytic core of the E2 enzyme UBE2M (Ubc12) in a similar manner to that in which ubiquitin interacts with ubiquitin binding domains.[3] # Interactions UBE1C has been shown to interact with NEDD8,[4] APPBP1[5] and UBE2M.[3]	https://www.wikidoc.org/index.php/UBE1C
88e61549c5b33817c0613e2560cabb291e8d02ab	wikidoc	UBE2I	UBE2I SUMO-conjugating enzyme UBC9 is an enzyme that in humans is encoded by the UBE2I gene. It is also sometimes referred to as "ubiquitin conjugating enzyme E2I" or "ubiquitin carrier protein 9", even though these names do not accurately describe its function. # Expression Four alternatively spliced transcript variants encoding the same protein have been found for this gene. # Function The UBC9 protein encoded by the UBE2I gene constitutes a core machinery in the cell's sumoylation pathway. Sumoylation is a process in which a Small Ubiquitin-like MOdifier (SUMO) is covalently attached to other proteins in order to modify their behaviour. For example, sumoylation may affect a protein's localization in the cell, its ability to interact with other proteins or DNA. UBC9 performs the third step in the sumoylation life cycle: the conjugation step. When SUMO protein precursors are first expressed, they first undergo a maturation step in which the four C-terminal amino acids are removed, revealing a di-glycine motif. In a second step, an E1 activating complex binds to SUMO at its di-glycine and passes it on to the E2 protein Ubc9, where it forms a thioester bond with a cysteine residue within Ubc9's catalytic pocket. The loaded Ubc9 is now ready to perform the sumoylation of its various target proteins (also called substrates). It recognizes a particular motif of amino acid residues in these substrates: A large hydrophobic residue, followed by a lysine, followed by a spacer, followed by an acidic residue. This motif is usually described in shorthand as ΨKxD/E. The central lysine within the substrate's recognition motif is inserted into the catalytic pocket. There the carbolxyl terminus of SUMO's di-glycine forms a peptide bond with the ε-amino group of the lysine. This process can be assisted by an E3 ligase protein. The sumoylation process is reversible. SENP proteases can remove SUMO from sumoylated proteins, freeing it to be used in further sumoylation reactions. # Clinical significance relevance The protein UBC9 encoded by the UBE2I gene has been shown to be targeted by multiple viruses, including HIV and HPV. It has been hypothesized that these viruses hijack UBC9 to serve their own purposes. # Interactions UBE2I has been shown to interact with: - ATF2, - Androgen receptor, - BLMH, - DACH1, - DNMT3A, - DNMT3B, - DAXX, - ETS1, - FHIT, - IPO13, - MAP3K1 and - MITF, - P53, - PIAS1, - PIAS2, - RAD51, - RANBP2, - RANGAP1, - SAE2, - SALL1, - SUMO1, - TCF3, - TNFRSF1A, - TOP1, and - WT1. # Notes - ↑ Watanabe TK, Fujiwara T, Kawai A, Shimizu F, Takami S, Hirano H, Okuno S, Ozaki K, Takeda S, Shimada Y, Nagata M, Takaichi A, Takahashi E, Nakamura Y, Shin S (March 1996). "Cloning, expression, and mapping of UBE2I, a novel gene encoding a human homologue of yeast ubiquitin-conjugating enzymes which are critical for regulating the cell cycle". Cytogenet Cell Genet. 72 (1): 86–9. doi:10.1159/000134169. PMID 8565643..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} - ↑ "Entrez Gene: UBE2I ubiquitin-conjugating enzyme E2I (UBC9 homolog, yeast)". - ↑ Varadaraj A, Mattoscio D, Chiocca S (Jan 2014). "SUMO Ubc9 enzyme as a viral target". IUBMB Life. 66 (1): 27–33. doi:10.1002/iub.1240. PMID 24395713. - ↑ Firestein R, Feuerstein N (March 1998). "Association of activating transcription factor 2 (ATF2) with the ubiquitin-conjugating enzyme hUBC9. Implication of the ubiquitin/proteasome pathway in regulation of ATF2 in T cells". J. Biol. Chem. 273 (10): 5892–902. doi:10.1074/jbc.273.10.5892. PMID 9488727. - ↑ Poukka H, Aarnisalo P, Karvonen U, Palvimo JJ, Jänne OA (July 1999). "Ubc9 interacts with the androgen receptor and activates receptor-dependent transcription". J. Biol. Chem. 274 (27): 19441–6. doi:10.1074/jbc.274.27.19441. PMID 10383460. - ↑ Koldamova RP, Lefterov IM, DiSabella MT, Lazo JS (Dec 1998). "An evolutionarily conserved cysteine protease, human bleomycin hydrolase, binds to the human homologue of ubiquitin-conjugating enzyme 9". Mol. Pharmacol. 54 (6): 954–61. PMID 9855622. - ↑ Jump up to: 7.0 7.1 Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, Berriz GF, Gibbons FD, Dreze M, Ayivi-Guedehoussou N, Klitgord N, Simon C, Boxem M, Milstein S, Rosenberg J, Goldberg DS, Zhang LV, Wong SL, Franklin G, Li S, Albala JS, Lim J, Fraughton C, Llamosas E, Cevik S, Bex C, Lamesch P, Sikorski RS, Vandenhaute J, Zoghbi HY, Smolyar A, Bosak S, Sequerra R, Doucette-Stamm L, Cusick ME, Hill DE, Roth FP, Vidal M (October 2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature. 437 (7062): 1173–8. doi:10.1038/nature04209. PMID 16189514. - ↑ Machon O, Backman M, Julin K, Krauss S (October 2000). "Yeast two-hybrid system identifies the ubiquitin-conjugating enzyme mUbc9 as a potential partner of mouse Dac". Mech. Dev. 97 (1–2): 3–12. doi:10.1016/s0925-4773(00)00402-0. PMID 11025202. - ↑ Ling Y, Sankpal UT, Robertson AK, McNally JG, Karpova T, Robertson KD. "Modification of de novo DNA methyltransferase 3a (Dnmt3a) by SUMO-1 modulates its interaction with histone deacetylases (HDACs) and its capacity to repress transcription". Nucleic Acids Res. 32 (2): 598–610. doi:10.1093/nar/gkh195. PMC 373322. PMID 14752048. - ↑ Kang ES, Park CW, Chung JH (Dec 2001). "Dnmt3b, de novo DNA methyltransferase, interacts with SUMO-1 and Ubc9 through its N-terminal region and is subject to modification by SUMO-1". Biochem. Biophys. Res. Commun. 289 (4): 862–8. doi:10.1006/bbrc.2001.6057. PMID 11735126. - ↑ Jump up to: 11.0 11.1 11.2 Knipscheer P, Flotho A, Klug H, Olsen JV, van Dijk WJ, Fish A, Johnson ES, Mann M, Sixma TK, Pichler A (August 2008). "Ubc9 sumoylation regulates SUMO target discrimination". Mol. Cell. 31 (3): 371–82. doi:10.1016/j.molcel.2008.05.022. PMID 18691969. - ↑ Ryu SW, Chae SK, Kim E (Dec 2000). "Interaction of Daxx, a Fas binding protein, with sentrin and Ubc9". Biochem. Biophys. Res. Commun. 279 (1): 6–10. doi:10.1006/bbrc.2000.3882. PMID 11112409. - ↑ Hahn SL, Wasylyk B, Criqui-Filipe P, Criqui P (September 1997). "Modulation of ETS-1 transcriptional activity by huUBC9, a ubiquitin-conjugating enzyme". Oncogene. 15 (12): 1489–95. doi:10.1038/sj.onc.1201301. PMID 9333025. - ↑ Shi Y, Zou M, Farid NR, Paterson MC (Dec 2000). "Association of FHIT (fragile histidine triad), a candidate tumour suppressor gene, with the ubiquitin-conjugating enzyme hUBC9". Biochem. J. 352 (2): 443–8. doi:10.1042/0264-6021:3520443. PMC 1221476. PMID 11085938. - ↑ Mingot JM, Kostka S, Kraft R, Hartmann E, Görlich D (July 2001). "Importin 13: a novel mediator of nuclear import and export". EMBO J. 20 (14): 3685–94. doi:10.1093/emboj/20.14.3685. PMC 125545. PMID 11447110. - ↑ Jump up to: 16.0 16.1 Saltzman A, Searfoss G, Marcireau C, Stone M, Ressner R, Munro R, Franks C, D'Alonzo J, Tocque B, Jaye M, Ivashchenko Y (April 1998). "hUBC9 associates with MEKK1 and type I TNF-alpha receptor and stimulates NFkappaB activity". FEBS Lett. 425 (3): 431–5. doi:10.1016/s0014-5793(98)00287-7. PMID 9563508. - ↑ Xu W, Gong L, Haddad MM, Bischof O, Campisi J, Yeh ET, Medrano EE (March 2000). "Regulation of microphthalmia-associated transcription factor MITF protein levels by association with the ubiquitin-conjugating enzyme hUBC9". Exp. Cell Res. 255 (2): 135–43. doi:10.1006/excr.2000.4803. PMID 10694430. - ↑ Jump up to: 18.0 18.1 18.2 Shen Z, Pardington-Purtymun PE, Comeaux JC, Moyzis RK, Chen DJ (October 1996). "Associations of UBE2I with RAD52, UBL1, p53, and RAD51 proteins in a yeast two-hybrid system". Genomics. 37 (2): 183–6. doi:10.1006/geno.1996.0540. PMID 8921390. - ↑ Jump up to: 19.0 19.1 Minty A, Dumont X, Kaghad M, Caput D (November 2000). "Covalent modification of p73alpha by SUMO-1. Two-hybrid screening with p73 identifies novel SUMO-1-interacting proteins and a SUMO-1 interaction motif". J. Biol. Chem. 275 (46): 36316–23. doi:10.1074/jbc.M004293200. PMID 10961991. - ↑ Gallagher WM, Argentini M, Sierra V, Bracco L, Debussche L, Conseiller E (June 1999). "MBP1: a novel mutant p53-specific protein partner with oncogenic properties". Oncogene. 18 (24): 3608–16. doi:10.1038/sj.onc.1202937. PMID 10380882. - ↑ Bernier-Villamor V, Sampson DA, Matunis MJ, Lima CD (February 2002). "Structural basis for E2-mediated SUMO conjugation revealed by a complex between ubiquitin-conjugating enzyme Ubc9 and RanGAP1". Cell. 108 (3): 345–56. doi:10.1016/s0092-8674(02)00630-x. PMID 11853669. - ↑ Jump up to: 22.0 22.1 Lee BH, Yoshimatsu K, Maeda A, Ochiai K, Morimatsu M, Araki K, Ogino M, Morikawa S, Arikawa J (Dec 2003). "Association of the nucleocapsid protein of the Seoul and Hantaan hantaviruses with small ubiquitin-like modifier-1-related molecules". Virus Res. 98 (1): 83–91. doi:10.1016/j.virusres.2003.09.001. PMID 14609633. - ↑ Sapetschnig A, Rischitor G, Braun H, Doll A, Schergaut M, Melchior F, Suske G (October 2002). "Transcription factor Sp3 is silenced through SUMO modification by PIAS1". EMBO J. 21 (19): 5206–15. doi:10.1093/emboj/cdf510. PMC 129032. PMID 12356736. - ↑ Kahyo T, Nishida T, Yasuda H (September 2001). "Involvement of PIAS1 in the sumoylation of tumor suppressor p53". Mol. Cell. 8 (3): 713–8. doi:10.1016/s1097-2765(01)00349-5. PMID 11583632. - ↑ Kovalenko OV, Plug AW, Haaf T, Gonda DK, Ashley T, Ward DC, Radding CM, Golub EI (April 1996). "Mammalian ubiquitin-conjugating enzyme Ubc9 interacts with Rad51 recombination protein and localizes in synaptonemal complexes". Proc. Natl. Acad. Sci. U.S.A. 93 (7): 2958–63. doi:10.1073/pnas.93.7.2958. PMC 39742. PMID 8610150. - ↑ Jump up to: 26.0 26.1 26.2 26.3 Ewing RM, Chu P, Elisma F, Li H, Taylor P, Climie S, McBroom-Cerajewski L, Robinson MD, O'Connor L, Li M, Taylor R, Dharsee M, Ho Y, Heilbut A, Moore L, Zhang S, Ornatsky O, Bukhman YV, Ethier M, Sheng Y, Vasilescu J, Abu-Farha M, Lambert JP, Duewel HS, Stewart II, Kuehl B, Hogue K, Colwill K, Gladwish K, Muskat B, Kinach R, Adams SL, Moran MF, Morin GB, Topaloglou T, Figeys D. "Large-scale mapping of human protein-protein interactions by mass spectrometry". Mol. Syst. Biol. 3: 89. doi:10.1038/msb4100134. PMC 1847948. PMID 17353931. - ↑ Zhang H, Saitoh H, Matunis MJ (September 2002). "Enzymes of the SUMO modification pathway localize to filaments of the nuclear pore complex". Mol. Cell. Biol. 22 (18): 6498–508. doi:10.1128/mcb.22.18.6498-6508.2002. PMC 135644. PMID 12192048. - ↑ Jump up to: 28.0 28.1 Tatham MH, Kim S, Yu B, Jaffray E, Song J, Zheng J, Rodriguez MS, Hay RT, Chen Y (August 2003). "Role of an N-terminal site of Ubc9 in SUMO-1, -2, and -3 binding and conjugation". Biochemistry. 42 (33): 9959–69. doi:10.1021/bi0345283. PMID 12924945. - ↑ Netzer C, Bohlander SK, Rieger L, Müller S, Kohlhase J (August 2002). "Interaction of the developmental regulator SALL1 with UBE2I and SUMO-1". Biochem. Biophys. Res. Commun. 296 (4): 870–6. doi:10.1016/s0006-291x(02)02003-x. PMID 12200128. - ↑ Huggins GS, Chin MT, Sibinga NE, Lee SL, Haber E, Lee ME (October 1999). "Characterization of the mUBC9-binding sites required for E2A protein degradation". J. Biol. Chem. 274 (40): 28690–6. doi:10.1074/jbc.274.40.28690. PMID 10497239. - ↑ Mao Y, Sun M, Desai SD, Liu LF (April 2000). "SUMO-1 conjugation to topoisomerase I: A possible repair response to topoisomerase-mediated DNA damage". Proc. Natl. Acad. Sci. U.S.A. 97 (8): 4046–51. doi:10.1073/pnas.080536597. PMC 18143. PMID 10759568. - ↑ Wang ZY, Qiu QQ, Seufert W, Taguchi T, Testa JR, Whitmore SA, Callen DF, Welsh D, Shenk T, Deuel TF (October 1996). "Molecular cloning of the cDNA and chromosome localization of the gene for human ubiquitin-conjugating enzyme 9". J. Biol. Chem. 271 (40): 24811–6. doi:10.1074/jbc.271.40.24811. PMID 8798754.	UBE2I SUMO-conjugating enzyme UBC9 is an enzyme that in humans is encoded by the UBE2I gene.[1] It is also sometimes referred to as "ubiquitin conjugating enzyme E2I" or "ubiquitin carrier protein 9", even though these names do not accurately describe its function. # Expression Four alternatively spliced transcript variants encoding the same protein have been found for this gene.[2] # Function The UBC9 protein encoded by the UBE2I gene constitutes a core machinery in the cell's sumoylation pathway. Sumoylation is a process in which a Small Ubiquitin-like MOdifier (SUMO) is covalently attached to other proteins in order to modify their behaviour. For example, sumoylation may affect a protein's localization in the cell, its ability to interact with other proteins or DNA. UBC9 performs the third step in the sumoylation life cycle: the conjugation step. When SUMO protein precursors are first expressed, they first undergo a maturation step in which the four C-terminal amino acids are removed, revealing a di-glycine motif. In a second step, an E1 activating complex binds to SUMO at its di-glycine and passes it on to the E2 protein Ubc9, where it forms a thioester bond with a cysteine residue within Ubc9's catalytic pocket. The loaded Ubc9 is now ready to perform the sumoylation of its various target proteins (also called substrates). It recognizes a particular motif of amino acid residues in these substrates: A large hydrophobic residue, followed by a lysine, followed by a spacer, followed by an acidic residue. This motif is usually described in shorthand as ΨKxD/E. The central lysine within the substrate's recognition motif is inserted into the catalytic pocket. There the carbolxyl terminus of SUMO's di-glycine forms a peptide bond with the ε-amino group of the lysine. This process can be assisted by an E3 ligase protein. The sumoylation process is reversible. SENP proteases can remove SUMO from sumoylated proteins, freeing it to be used in further sumoylation reactions. # Clinical significance relevance The protein UBC9 encoded by the UBE2I gene has been shown to be targeted by multiple viruses, including HIV and HPV. It has been hypothesized that these viruses hijack UBC9 to serve their own purposes.[3] # Interactions UBE2I has been shown to interact with: - ATF2,[4] - Androgen receptor,[5] - BLMH,[6] - DACH1,[7][8] - DNMT3A,[9] - DNMT3B,[10] - DAXX,[11][12] - ETS1,[13] - FHIT,[14] - IPO13,[15] - MAP3K1[16] and - MITF,[17] - P53,[18][19][20][21] - PIAS1,[22][23][24] - PIAS2,[7][22] - RAD51,[18][25] - RANBP2,[26][27] - RANGAP1,[11][26][28] - SAE2,[11][26] - SALL1,[29] - SUMO1,[18][19][26][28] - TCF3,[30] - TNFRSF1A,[16] - TOP1,[31] and - WT1.[32] # Notes - ↑ Watanabe TK, Fujiwara T, Kawai A, Shimizu F, Takami S, Hirano H, Okuno S, Ozaki K, Takeda S, Shimada Y, Nagata M, Takaichi A, Takahashi E, Nakamura Y, Shin S (March 1996). "Cloning, expression, and mapping of UBE2I, a novel gene encoding a human homologue of yeast ubiquitin-conjugating enzymes which are critical for regulating the cell cycle". Cytogenet Cell Genet. 72 (1): 86–9. doi:10.1159/000134169. PMID 8565643..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} - ↑ "Entrez Gene: UBE2I ubiquitin-conjugating enzyme E2I (UBC9 homolog, yeast)". - ↑ Varadaraj A, Mattoscio D, Chiocca S (Jan 2014). "SUMO Ubc9 enzyme as a viral target". IUBMB Life. 66 (1): 27–33. doi:10.1002/iub.1240. PMID 24395713. - ↑ Firestein R, Feuerstein N (March 1998). "Association of activating transcription factor 2 (ATF2) with the ubiquitin-conjugating enzyme hUBC9. Implication of the ubiquitin/proteasome pathway in regulation of ATF2 in T cells". J. Biol. Chem. 273 (10): 5892–902. doi:10.1074/jbc.273.10.5892. PMID 9488727. - ↑ Poukka H, Aarnisalo P, Karvonen U, Palvimo JJ, Jänne OA (July 1999). "Ubc9 interacts with the androgen receptor and activates receptor-dependent transcription". J. Biol. Chem. 274 (27): 19441–6. doi:10.1074/jbc.274.27.19441. PMID 10383460. - ↑ Koldamova RP, Lefterov IM, DiSabella MT, Lazo JS (Dec 1998). "An evolutionarily conserved cysteine protease, human bleomycin hydrolase, binds to the human homologue of ubiquitin-conjugating enzyme 9". Mol. Pharmacol. 54 (6): 954–61. PMID 9855622. - ↑ Jump up to: 7.0 7.1 Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, Berriz GF, Gibbons FD, Dreze M, Ayivi-Guedehoussou N, Klitgord N, Simon C, Boxem M, Milstein S, Rosenberg J, Goldberg DS, Zhang LV, Wong SL, Franklin G, Li S, Albala JS, Lim J, Fraughton C, Llamosas E, Cevik S, Bex C, Lamesch P, Sikorski RS, Vandenhaute J, Zoghbi HY, Smolyar A, Bosak S, Sequerra R, Doucette-Stamm L, Cusick ME, Hill DE, Roth FP, Vidal M (October 2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature. 437 (7062): 1173–8. doi:10.1038/nature04209. PMID 16189514. - ↑ Machon O, Backman M, Julin K, Krauss S (October 2000). "Yeast two-hybrid system identifies the ubiquitin-conjugating enzyme mUbc9 as a potential partner of mouse Dac". Mech. Dev. 97 (1–2): 3–12. doi:10.1016/s0925-4773(00)00402-0. PMID 11025202. - ↑ Ling Y, Sankpal UT, Robertson AK, McNally JG, Karpova T, Robertson KD. "Modification of de novo DNA methyltransferase 3a (Dnmt3a) by SUMO-1 modulates its interaction with histone deacetylases (HDACs) and its capacity to repress transcription". Nucleic Acids Res. 32 (2): 598–610. doi:10.1093/nar/gkh195. PMC 373322. PMID 14752048. - ↑ Kang ES, Park CW, Chung JH (Dec 2001). "Dnmt3b, de novo DNA methyltransferase, interacts with SUMO-1 and Ubc9 through its N-terminal region and is subject to modification by SUMO-1". Biochem. Biophys. Res. Commun. 289 (4): 862–8. doi:10.1006/bbrc.2001.6057. PMID 11735126. - ↑ Jump up to: 11.0 11.1 11.2 Knipscheer P, Flotho A, Klug H, Olsen JV, van Dijk WJ, Fish A, Johnson ES, Mann M, Sixma TK, Pichler A (August 2008). "Ubc9 sumoylation regulates SUMO target discrimination". Mol. Cell. 31 (3): 371–82. doi:10.1016/j.molcel.2008.05.022. PMID 18691969. - ↑ Ryu SW, Chae SK, Kim E (Dec 2000). "Interaction of Daxx, a Fas binding protein, with sentrin and Ubc9". Biochem. Biophys. Res. Commun. 279 (1): 6–10. doi:10.1006/bbrc.2000.3882. PMID 11112409. - ↑ Hahn SL, Wasylyk B, Criqui-Filipe P, Criqui P (September 1997). "Modulation of ETS-1 transcriptional activity by huUBC9, a ubiquitin-conjugating enzyme". Oncogene. 15 (12): 1489–95. doi:10.1038/sj.onc.1201301. PMID 9333025. - ↑ Shi Y, Zou M, Farid NR, Paterson MC (Dec 2000). "Association of FHIT (fragile histidine triad), a candidate tumour suppressor gene, with the ubiquitin-conjugating enzyme hUBC9". Biochem. J. 352 (2): 443–8. doi:10.1042/0264-6021:3520443. PMC 1221476. PMID 11085938. - ↑ Mingot JM, Kostka S, Kraft R, Hartmann E, Görlich D (July 2001). "Importin 13: a novel mediator of nuclear import and export". EMBO J. 20 (14): 3685–94. doi:10.1093/emboj/20.14.3685. PMC 125545. PMID 11447110. - ↑ Jump up to: 16.0 16.1 Saltzman A, Searfoss G, Marcireau C, Stone M, Ressner R, Munro R, Franks C, D'Alonzo J, Tocque B, Jaye M, Ivashchenko Y (April 1998). "hUBC9 associates with MEKK1 and type I TNF-alpha receptor and stimulates NFkappaB activity". FEBS Lett. 425 (3): 431–5. doi:10.1016/s0014-5793(98)00287-7. PMID 9563508. - ↑ Xu W, Gong L, Haddad MM, Bischof O, Campisi J, Yeh ET, Medrano EE (March 2000). "Regulation of microphthalmia-associated transcription factor MITF protein levels by association with the ubiquitin-conjugating enzyme hUBC9". Exp. Cell Res. 255 (2): 135–43. doi:10.1006/excr.2000.4803. PMID 10694430. - ↑ Jump up to: 18.0 18.1 18.2 Shen Z, Pardington-Purtymun PE, Comeaux JC, Moyzis RK, Chen DJ (October 1996). "Associations of UBE2I with RAD52, UBL1, p53, and RAD51 proteins in a yeast two-hybrid system". Genomics. 37 (2): 183–6. doi:10.1006/geno.1996.0540. PMID 8921390. - ↑ Jump up to: 19.0 19.1 Minty A, Dumont X, Kaghad M, Caput D (November 2000). "Covalent modification of p73alpha by SUMO-1. Two-hybrid screening with p73 identifies novel SUMO-1-interacting proteins and a SUMO-1 interaction motif". J. Biol. Chem. 275 (46): 36316–23. doi:10.1074/jbc.M004293200. PMID 10961991. - ↑ Gallagher WM, Argentini M, Sierra V, Bracco L, Debussche L, Conseiller E (June 1999). "MBP1: a novel mutant p53-specific protein partner with oncogenic properties". Oncogene. 18 (24): 3608–16. doi:10.1038/sj.onc.1202937. PMID 10380882. - ↑ Bernier-Villamor V, Sampson DA, Matunis MJ, Lima CD (February 2002). "Structural basis for E2-mediated SUMO conjugation revealed by a complex between ubiquitin-conjugating enzyme Ubc9 and RanGAP1". Cell. 108 (3): 345–56. doi:10.1016/s0092-8674(02)00630-x. PMID 11853669. - ↑ Jump up to: 22.0 22.1 Lee BH, Yoshimatsu K, Maeda A, Ochiai K, Morimatsu M, Araki K, Ogino M, Morikawa S, Arikawa J (Dec 2003). "Association of the nucleocapsid protein of the Seoul and Hantaan hantaviruses with small ubiquitin-like modifier-1-related molecules". Virus Res. 98 (1): 83–91. doi:10.1016/j.virusres.2003.09.001. PMID 14609633. - ↑ Sapetschnig A, Rischitor G, Braun H, Doll A, Schergaut M, Melchior F, Suske G (October 2002). "Transcription factor Sp3 is silenced through SUMO modification by PIAS1". EMBO J. 21 (19): 5206–15. doi:10.1093/emboj/cdf510. PMC 129032. PMID 12356736. - ↑ Kahyo T, Nishida T, Yasuda H (September 2001). "Involvement of PIAS1 in the sumoylation of tumor suppressor p53". Mol. Cell. 8 (3): 713–8. doi:10.1016/s1097-2765(01)00349-5. PMID 11583632. - ↑ Kovalenko OV, Plug AW, Haaf T, Gonda DK, Ashley T, Ward DC, Radding CM, Golub EI (April 1996). "Mammalian ubiquitin-conjugating enzyme Ubc9 interacts with Rad51 recombination protein and localizes in synaptonemal complexes". Proc. Natl. Acad. Sci. U.S.A. 93 (7): 2958–63. doi:10.1073/pnas.93.7.2958. PMC 39742. PMID 8610150. - ↑ Jump up to: 26.0 26.1 26.2 26.3 Ewing RM, Chu P, Elisma F, Li H, Taylor P, Climie S, McBroom-Cerajewski L, Robinson MD, O'Connor L, Li M, Taylor R, Dharsee M, Ho Y, Heilbut A, Moore L, Zhang S, Ornatsky O, Bukhman YV, Ethier M, Sheng Y, Vasilescu J, Abu-Farha M, Lambert JP, Duewel HS, Stewart II, Kuehl B, Hogue K, Colwill K, Gladwish K, Muskat B, Kinach R, Adams SL, Moran MF, Morin GB, Topaloglou T, Figeys D. "Large-scale mapping of human protein-protein interactions by mass spectrometry". Mol. Syst. Biol. 3: 89. doi:10.1038/msb4100134. PMC 1847948. PMID 17353931. - ↑ Zhang H, Saitoh H, Matunis MJ (September 2002). "Enzymes of the SUMO modification pathway localize to filaments of the nuclear pore complex". Mol. Cell. Biol. 22 (18): 6498–508. doi:10.1128/mcb.22.18.6498-6508.2002. PMC 135644. PMID 12192048. - ↑ Jump up to: 28.0 28.1 Tatham MH, Kim S, Yu B, Jaffray E, Song J, Zheng J, Rodriguez MS, Hay RT, Chen Y (August 2003). "Role of an N-terminal site of Ubc9 in SUMO-1, -2, and -3 binding and conjugation". Biochemistry. 42 (33): 9959–69. doi:10.1021/bi0345283. PMID 12924945. - ↑ Netzer C, Bohlander SK, Rieger L, Müller S, Kohlhase J (August 2002). "Interaction of the developmental regulator SALL1 with UBE2I and SUMO-1". Biochem. Biophys. Res. Commun. 296 (4): 870–6. doi:10.1016/s0006-291x(02)02003-x. PMID 12200128. - ↑ Huggins GS, Chin MT, Sibinga NE, Lee SL, Haber E, Lee ME (October 1999). "Characterization of the mUBC9-binding sites required for E2A protein degradation". J. Biol. Chem. 274 (40): 28690–6. doi:10.1074/jbc.274.40.28690. PMID 10497239. - ↑ Mao Y, Sun M, Desai SD, Liu LF (April 2000). "SUMO-1 conjugation to topoisomerase I: A possible repair response to topoisomerase-mediated DNA damage". Proc. Natl. Acad. Sci. U.S.A. 97 (8): 4046–51. doi:10.1073/pnas.080536597. PMC 18143. PMID 10759568. - ↑ Wang ZY, Qiu QQ, Seufert W, Taguchi T, Testa JR, Whitmore SA, Callen DF, Welsh D, Shenk T, Deuel TF (October 1996). "Molecular cloning of the cDNA and chromosome localization of the gene for human ubiquitin-conjugating enzyme 9". J. Biol. Chem. 271 (40): 24811–6. doi:10.1074/jbc.271.40.24811. PMID 8798754.	https://www.wikidoc.org/index.php/UBE2I
2db51aab47459c140f63eff55b311541629e08c7	wikidoc	UBE2M	UBE2M NEDD8-conjugating enzyme Ubc12 is a protein that in humans is encoded by the UBE2M gene. The modification of proteins with ubiquitin is an important cellular mechanism for targeting abnormal or short-lived proteins for degradation. Ubiquitination involves at least three classes of enzymes: ubiquitin-activating enzymes, or E1s, ubiquitin-conjugating enzymes, or E2s, and ubiquitin-protein ligases, or E3s. This gene encodes a member of the E2 ubiquitin-conjugating enzyme family. The encoded protein is linked with a ubiquitin-like protein, NEDD8, which can be conjugated to cellular proteins, such as Cdc53/culin. # Interactions UBE2M has been shown to interact with NEDD8, PRKAR1A and UBA3.	UBE2M NEDD8-conjugating enzyme Ubc12 is a protein that in humans is encoded by the UBE2M gene.[1][2] The modification of proteins with ubiquitin is an important cellular mechanism for targeting abnormal or short-lived proteins for degradation. Ubiquitination involves at least three classes of enzymes: ubiquitin-activating enzymes, or E1s, ubiquitin-conjugating enzymes, or E2s, and ubiquitin-protein ligases, or E3s. This gene encodes a member of the E2 ubiquitin-conjugating enzyme family. The encoded protein is linked with a ubiquitin-like protein, NEDD8, which can be conjugated to cellular proteins, such as Cdc53/culin.[2] # Interactions UBE2M has been shown to interact with NEDD8,[3] PRKAR1A[4] and UBA3.[5]	https://www.wikidoc.org/index.php/UBE2M
b5a8db747af85b4f865e6fd0d71cde05f7820b81	wikidoc	UBE2Z	UBE2Z Ubiquitin conjugating enzyme E2 Z (UBE2Z), also known as UBA6-specific E2 enzyme 1 (USE1), is an enzyme that in humans is encoded by the UBE2Z gene on chromosome 17. It is ubiquitously expressed in many tissues and cell types. UBE2Z is an E2 ubiquitin conjugating enzyme and participates in the second step of protein ubiquitination during proteolysis. A genome-wide association study (GWAS) revealed the UBE2Z gene to be associated with chronic kidney disease. The UBE2Z gene also contains one of 27 SNPs associated with increased risk of coronary artery disease. # Structure ## Gene The UBE2Z gene resides on chromosome 17 at the band 17q21.32 and contains 7 exons. This gene produces 2 isoforms through alternative splicing. The UBE2Z cDNA spans a length of 3,054 base pairs. ## Protein This protein belongs to the ubiquitin conjugating enzyme family and is one of the E2 enzymes. UBE2Z spans 246 amino acids, 150 of which encode a conserved 16–18 kDa ubiquitin conjugating enzyme E2 domain (UBC domain) that is located at the enzyme’s N-terminal and responsible for the enzyme’s catalytic function. This UBC domain has a relatively inflexible β-sheet structure with flanking helices and contains a highly conserved cysteine residue, Cys80, which functions as an active site for the thiol ester formation with ubiquitin. UBE2Z also contains a C-terminal extension, suggested to participate in substrate binding, which is characteristic of a class II E2 ubiquitin conjugating enzyme. # Function The UBE2Z gene is ubiquitously expressed in human tissues, and its expression is relatively high in placenta, pancreas, spleen and testis. Notably, its expression in cancer tissues is much higher than in relevant normal tissues, especially in kidney, lymph node, colon and ovary cancer. As an E2 member of the ubiquitin-conjugating enzyme family, UBE2Z mainly participates in the second step of protein ubiquitination, which is a major component of protein degradation machinery. Specifically, UBE2Z receives ubiquitin (Ub) from ubiquitin-activating enzyme (E1), mediates the transfer of Ub from E2 to substrate, directly or indirectly with the help of ligase enzyme (E3), which interacts with the substrate and E2-Ub complex. UBE2Z could only be charged by Ub or FAT10 from UBA6 instead of UBA1, distinguishing it from other E2s. # Clinical significance A study in genetic variants that regulate lipid metabolism and determine the susceptibility to dyslipidemia in Japanese individuals revealed that UBE2Z, together with ZPR1 and Interleukin-6R, may be important loci for hypertriglyceridemia. Moreover, in a GWAS among 2247 Japanese individuals, 29 polymorphisms that were previously identified as susceptible loci for coronary artery disease were investigated to identify a correlation of these loci to chronic kidney disease. This GWAS meta-analysis revealed through a chi-square test that rs46522 on the UBE2Z gene was significantly related to chronic kidney disease. ## Clinical marker A multi-locus genetic risk score study based on a combination of 27 loci, including the UBE2Z gene, identified individuals at increased risk for both incident and recurrent coronary artery disease events, as well as an enhanced clinical benefit from statin therapy. The study was based on a community cohort study (the Malmo Diet and Cancer study) and four additional randomized controlled trials of primary prevention cohorts (JUPITER and ASCOT) and secondary prevention cohorts (CARE and PROVE IT-TIMI 22).	UBE2Z Ubiquitin conjugating enzyme E2 Z (UBE2Z), also known as UBA6-specific E2 enzyme 1 (USE1), is an enzyme that in humans is encoded by the UBE2Z gene on chromosome 17.[1][2] It is ubiquitously expressed in many tissues and cell types.[3] UBE2Z is an E2 ubiquitin conjugating enzyme and participates in the second step of protein ubiquitination during proteolysis.[4] A genome-wide association study (GWAS) revealed the UBE2Z gene to be associated with chronic kidney disease.[5] The UBE2Z gene also contains one of 27 SNPs associated with increased risk of coronary artery disease.[6] # Structure ## Gene The UBE2Z gene resides on chromosome 17 at the band 17q21.32 and contains 7 exons.[1] This gene produces 2 isoforms through alternative splicing.[7] The UBE2Z cDNA spans a length of 3,054 base pairs.[8] ## Protein This protein belongs to the ubiquitin conjugating enzyme family and is one of the E2 enzymes.[7] UBE2Z spans 246 amino acids, 150 of which encode a conserved 16–18 kDa ubiquitin conjugating enzyme E2 domain (UBC domain) that is located at the enzyme’s N-terminal and responsible for the enzyme’s catalytic function. This UBC domain has a relatively inflexible β-sheet structure with flanking helices and contains a highly conserved cysteine residue, Cys80, which functions as an active site for the thiol ester formation with ubiquitin. UBE2Z also contains a C-terminal extension, suggested to participate in substrate binding, which is characteristic of a class II E2 ubiquitin conjugating enzyme.[8] # Function The UBE2Z gene is ubiquitously expressed in human tissues, and its expression is relatively high in placenta, pancreas, spleen and testis. Notably, its expression in cancer tissues is much higher than in relevant normal tissues, especially in kidney, lymph node, colon and ovary cancer.[8] As an E2 member of the ubiquitin-conjugating enzyme family, UBE2Z mainly participates in the second step of protein ubiquitination, which is a major component of protein degradation machinery.[4] Specifically, UBE2Z receives ubiquitin (Ub) from ubiquitin-activating enzyme (E1), mediates the transfer of Ub from E2 to substrate, directly or indirectly with the help of ligase enzyme (E3), which interacts with the substrate and E2-Ub complex. UBE2Z could only be charged by Ub or FAT10 from UBA6 instead of UBA1, distinguishing it from other E2s.[9][10] # Clinical significance A study in genetic variants that regulate lipid metabolism and determine the susceptibility to dyslipidemia in Japanese individuals revealed that UBE2Z, together with ZPR1 and Interleukin-6R, may be important loci for hypertriglyceridemia.[11] Moreover, in a GWAS among 2247 Japanese individuals, 29 polymorphisms that were previously identified as susceptible loci for coronary artery disease were investigated to identify a correlation of these loci to chronic kidney disease.[5] This GWAS meta-analysis revealed through a chi-square test that rs46522 on the UBE2Z gene was significantly related to chronic kidney disease.[5] ## Clinical marker A multi-locus genetic risk score study based on a combination of 27 loci, including the UBE2Z gene, identified individuals at increased risk for both incident and recurrent coronary artery disease events, as well as an enhanced clinical benefit from statin therapy. The study was based on a community cohort study (the Malmo Diet and Cancer study) and four additional randomized controlled trials of primary prevention cohorts (JUPITER and ASCOT) and secondary prevention cohorts (CARE and PROVE IT-TIMI 22).[6]	https://www.wikidoc.org/index.php/UBE2Z
88f56e34879eede8eeb4ec1903808f32e00f8044	wikidoc	UBE3A	UBE3A Ubiquitin-protein ligase E3A (UBE3A) also known as E6AP ubiquitin-protein ligase (E6AP) is an enzyme that in humans is encoded by the UBE3A gene. This enzyme is involved in targeting proteins for degradation within cells. Protein degradation is a normal process that removes damaged or unnecessary proteins and helps maintain the normal functions of cells. Ubiquitin protein ligase E3A attaches a small marker protein called ubiquitin to proteins that should be degraded. Cellular structures called proteasomes recognize and digest proteins tagged with ubiquitin. Both copies of the UBE3A gene are active in most of the body's tissues. In most neurons, however, only the copy inherited from a person's mother (the maternal copy) is normally active; this is known as paternal imprinting. Recent evidence shows that at least some glial cells and neurons may exhibit biallelic expression of UBE3A. Further work is thus needed to delineate a complete map of UBE3A imprinting in humans and model organisms such as mice. Silencing of Ube3a on the paternal allele is thought to occur through the Ube3a-ATS part of a lincRNA called "LNCAT", (Large Non-Coding Antisense Transcript). The UBE3A gene is located on the long (q) arm of chromosome 15 between positions 11 and 13, from base pair 23,133,488 to base pair 23,235,220. # Clinical significance Mutations within the UBE3A gene are responsible for some cases of Angelman syndrome and Prader-Willi syndrome. Most of these mutations result in an abnormally short, nonfunctional version of ubiquitin protein ligase E3A. Because the copy of the gene inherited from a person's father (the paternal copy) is normally inactive in the brain, a mutation in the remaining maternal copy prevents any of the enzyme from being produced in the brain. This loss of enzyme function likely causes the characteristic features of these two conditions. The UBE3A gene lies within the human chromosomal region 15q11-13. Other abnormalities in this region of chromosome 15 can also cause Angelman syndrome. These chromosomal changes include deletions, rearrangements (translocations) of genetic material, and other abnormalities. Like mutations within the gene, these chromosomal changes prevent any functional ubiquitin protein ligase E3A from being produced in the brain. # Interactions UBE3A has been shown to interact with: - BLK, - Lck, - MCM7, - MECP2, - Progesterone receptor, - TSC2, - UBE2D1, - UBE2D2, - UBE2L3, - UBQLN1, and - UBQLN2.	UBE3A Ubiquitin-protein ligase E3A (UBE3A) also known as E6AP ubiquitin-protein ligase (E6AP) is an enzyme that in humans is encoded by the UBE3A gene. This enzyme is involved in targeting proteins for degradation within cells. Protein degradation is a normal process that removes damaged or unnecessary proteins and helps maintain the normal functions of cells. Ubiquitin protein ligase E3A attaches a small marker protein called ubiquitin to proteins that should be degraded. Cellular structures called proteasomes recognize and digest proteins tagged with ubiquitin. Both copies of the UBE3A gene are active in most of the body's tissues. In most neurons, however, only the copy inherited from a person's mother (the maternal copy) is normally active; this is known as paternal imprinting. Recent evidence shows that at least some glial cells and neurons may exhibit biallelic expression of UBE3A.[1][2] Further work is thus needed to delineate a complete map of UBE3A imprinting in humans and model organisms such as mice. Silencing of Ube3a on the paternal allele is thought to occur through the Ube3a-ATS part of a lincRNA called "LNCAT",[3] (Large Non-Coding Antisense Transcript). The UBE3A gene is located on the long (q) arm of chromosome 15 between positions 11 and 13, from base pair 23,133,488 to base pair 23,235,220. # Clinical significance Mutations within the UBE3A gene are responsible for some cases of Angelman syndrome and Prader-Willi syndrome. Most of these mutations result in an abnormally short, nonfunctional version of ubiquitin protein ligase E3A. Because the copy of the gene inherited from a person's father (the paternal copy) is normally inactive in the brain, a mutation in the remaining maternal copy prevents any of the enzyme from being produced in the brain. This loss of enzyme function likely causes the characteristic features of these two conditions. The UBE3A gene lies within the human chromosomal region 15q11-13. Other abnormalities in this region of chromosome 15 can also cause Angelman syndrome. These chromosomal changes include deletions, rearrangements (translocations) of genetic material, and other abnormalities. Like mutations within the gene, these chromosomal changes prevent any functional ubiquitin protein ligase E3A from being produced in the brain. # Interactions UBE3A has been shown to interact with: - BLK,[4] - Lck,[4] - MCM7,[5] - MECP2,[6] - Progesterone receptor,[7] - TSC2,[8][9] - UBE2D1,[10][11] - UBE2D2,[12][13] - UBE2L3,[10][12][14] - UBQLN1,[15] and - UBQLN2.[15]	https://www.wikidoc.org/index.php/UBE3A
6361d7c5265a30a93024d2a9ffd341a1cf9f8f21	wikidoc	UBXD5	UBXD5 UBX domain-containing protein 11 is a protein that in humans is encoded by the UBXN11 gene. # Function This gene encodes a protein with a divergent C-terminal UBX domain. The homologous protein in the rat interacts with members of the Rnd subfamily of Rho GTPases at the cell periphery through its C-terminal region. It also interacts with several heterotrimeric G proteins through their G-alpha subunits and promotes Rho GTPase activation. It is proposed to serve a bidirectional role in the promotion and inhibition of Rho activity through upstream signaling pathways. The 3' coding sequence of this gene contains a polymoprhic region of 24 nt tandem repeats. Several transcripts containing between 1.5 and five repeat units have been reported. Multiple transcript variants encoding different isoforms have been found for this gene. # Interactions UBXD5 has been shown to interact with Rnd1, Rnd2 and Rnd3.	UBXD5 UBX domain-containing protein 11 is a protein that in humans is encoded by the UBXN11 gene.[1][2] # Function This gene encodes a protein with a divergent C-terminal UBX domain. The homologous protein in the rat interacts with members of the Rnd subfamily of Rho GTPases at the cell periphery through its C-terminal region. It also interacts with several heterotrimeric G proteins through their G-alpha subunits and promotes Rho GTPase activation. It is proposed to serve a bidirectional role in the promotion and inhibition of Rho activity through upstream signaling pathways. The 3' coding sequence of this gene contains a polymoprhic region of 24 nt tandem repeats. Several transcripts containing between 1.5 and five repeat units have been reported. Multiple transcript variants encoding different isoforms have been found for this gene.[2] # Interactions UBXD5 has been shown to interact with Rnd1,[1] Rnd2[1] and Rnd3.[1]	https://www.wikidoc.org/index.php/UBXD5
6bc31c9b809e3a3d714b21ad5c87b4c5748901e5	wikidoc	UHMK1	UHMK1 U2AF homology motif (UHM) kinase 1, also known as UHMK1, is a protein which in humans is encoded by the UHMK1 gene. # Function UHMK1 is a kinase enzyme which phosphorylates the protein stathmin and has an RNA recognition motif of unknown function. # Clinical significance UHMK1 is highly expressed in the brain and has been genetically implicated in schizophrenia in two genetic studies. Mice with the gene encoding stathmin knocked out, so that they do not express this protein in the brain, show abnormal fear responses. This effect could be developed as an animal model for schizophrenia. UHMK1 also phosphorylates the CNS proteins myelin basic protein (MBP) and synapsin I so that genetic abnormalities in UHMK1 could contribute to the genetic cause of schizophrenia through several different brain pathways.	UHMK1 U2AF homology motif (UHM) kinase 1, also known as UHMK1, is a protein which in humans is encoded by the UHMK1 gene.[1][2] # Function UHMK1 is a kinase enzyme which phosphorylates the protein stathmin and has an RNA recognition motif of unknown function.[3] # Clinical significance UHMK1 is highly expressed in the brain and has been genetically implicated in schizophrenia in two genetic studies.[4][5] Mice with the gene encoding stathmin knocked out, so that they do not express this protein in the brain, show abnormal fear responses. This effect could be developed as an animal model for schizophrenia.[6] UHMK1 also phosphorylates the CNS proteins myelin basic protein (MBP) and synapsin I so that genetic abnormalities in UHMK1 could contribute to the genetic cause of schizophrenia through several different brain pathways.	https://www.wikidoc.org/index.php/UHMK1
3d55618cf0787606d27c814a986c6493d091a229	wikidoc	UHRF1	UHRF1 Ubiquitin-like, containing PHD and RING finger domains, 1, also known as UHRF1, is a protein which in humans is encoded by the UHRF1 gene. # Function This gene encodes a member of a subfamily of RING-finger type E3 ubiquitin ligases. The protein binds to hemi-methylated DNA during S-phase and recruits the main DNA methyltransferase gene, DNMT1, to regulate chromatin structure and gene expression. Its expression peaks at late G1 phase and continues during G2 and M phases of the cell cycle. It plays a major role in the G1/S transition, and functions in the p53-dependent DNA damage checkpoint. Multiple transcript variants encoding different isoforms have been found for this gene. It was originally identified as a direct regulator of topoisomerase 2a, but this has subsequently been disproven. Uhrf1 has been extensively studied in vivo using zebrafish. # Clinical significance UHRF1 has recently been identified as a novel oncogene in hepatocellular carcinoma, the primary type of liver cancer.	UHRF1 Ubiquitin-like, containing PHD and RING finger domains, 1, also known as UHRF1, is a protein which in humans is encoded by the UHRF1 gene.[1][2] # Function This gene encodes a member of a subfamily of RING-finger type E3 ubiquitin ligases. The protein binds to hemi-methylated DNA during S-phase and recruits the main DNA methyltransferase gene, DNMT1, to regulate chromatin structure and gene expression. Its expression peaks at late G1 phase and continues during G2 and M phases of the cell cycle. It plays a major role in the G1/S transition, and functions in the p53-dependent DNA damage checkpoint. Multiple transcript variants encoding different isoforms have been found for this gene. It was originally identified as a direct regulator of topoisomerase 2a, but this has subsequently been disproven. Uhrf1 has been extensively studied in vivo using zebrafish. # Clinical significance UHRF1 has recently been identified as a novel oncogene in hepatocellular carcinoma, the primary type of liver cancer.[3]	https://www.wikidoc.org/index.php/UHRF1
b3931ffc547d4aa6a51dcec93a5adf844161f5c1	wikidoc	UQCC2	UQCC2 Ubiquinol-cytochrome c reductase complex assembly factor 2 is a protein that in humans is encoded by the UQCC2 gene. Located in the mitochondrial nucleoid, this protein is a complex III assembly factor, playing a role in cytochrome b biogenesis along with the UQCC1 protein. It regulates insulin secretion and mitochondrial ATP production and oxygen consumption. In the sole recorded case, a mutation in the UQCC2 gene caused Complex III deficiency, characterized by intrauterine growth retardation, neonatal lactic acidosis, and renal tubular dysfunction. # Structure The UQCC2 gene is located on the p arm of chromosome 6 in position 21.31 and spans 14,990 base pairs. The gene produces a 14.9 kDa protein composed of 126 amino acids. This protein has no homologous domains with other known proteins. It is associated with the mitochondrial nucleoid, likely located in the peripheral region. This protein's distribution pattern is similar to other components of the mitochondrial nucleoid, like mtSSB and PHB1/PHB2. # Function This gene encodes a nucleoid protein localized to the mitochondrial inner membrane and sublocalized to the mitochondrial matrix. The encoded protein permissively regulates insulin secretion in pancreatic beta cells, positively regulates mitochondrial ATP production and oxygen consumption, and is involved in late skeletal muscle differentiation through modulation of mitochondrial respiratory chain activity. This protein is required for the assembly of the Complex III. Expression of this protein is decreased in cells with low mtDNA. # Clinical Significance In the sole recorded case, a homozygous mutation in intron 2 of the UQCC2 gene caused a splicing disruption; the patient presented with symptoms of nuclear type 7 Complex III deficiency, including neonatal lactic acidosis, renal tubulopathy, and severe intrauterine growth retardation. Additional clinical features included a dysmorphic facial appearance, delayed psychomotor development, autistic features, aggressive behavior, and mild sensorineural hearing loss. Additionally, the patient had decreased levels of UQCC1. # Interactions This protein interacts with UQCC1.	UQCC2 Ubiquinol-cytochrome c reductase complex assembly factor 2 is a protein that in humans is encoded by the UQCC2 gene. Located in the mitochondrial nucleoid, this protein is a complex III assembly factor, playing a role in cytochrome b biogenesis along with the UQCC1 protein.[1] It regulates insulin secretion and mitochondrial ATP production and oxygen consumption.[2][3] In the sole recorded case, a mutation in the UQCC2 gene caused Complex III deficiency, characterized by intrauterine growth retardation, neonatal lactic acidosis, and renal tubular dysfunction.[4] # Structure The UQCC2 gene is located on the p arm of chromosome 6 in position 21.31 and spans 14,990 base pairs.[1] The gene produces a 14.9 kDa protein composed of 126 amino acids.[5][6] This protein has no homologous domains with other known proteins. It is associated with the mitochondrial nucleoid, likely located in the peripheral region.[3] This protein's distribution pattern is similar to other components of the mitochondrial nucleoid, like mtSSB and PHB1/PHB2.[7] # Function This gene encodes a nucleoid protein localized to the mitochondrial inner membrane and sublocalized to the mitochondrial matrix.[7] The encoded protein permissively regulates insulin secretion in pancreatic beta cells, positively regulates mitochondrial ATP production and oxygen consumption, and is involved in late skeletal muscle differentiation through modulation of mitochondrial respiratory chain activity.[3] This protein is required for the assembly of the Complex III. Expression of this protein is decreased in cells with low mtDNA.[7] # Clinical Significance In the sole recorded case, a homozygous mutation in intron 2 of the UQCC2 gene caused a splicing disruption; the patient presented with symptoms of nuclear type 7 Complex III deficiency, including neonatal lactic acidosis, renal tubulopathy, and severe intrauterine growth retardation. Additional clinical features included a dysmorphic facial appearance, delayed psychomotor development, autistic features, aggressive behavior, and mild sensorineural hearing loss.[2] Additionally, the patient had decreased levels of UQCC1.[4] # Interactions This protein interacts with UQCC1.[2]	https://www.wikidoc.org/index.php/UQCC2
e39cf5b43f879853a954c00b49ba86b6192c39e0	wikidoc	UQCC3	UQCC3 Ubiquinol-cytochrome c reductase complex assembly factor 3 is a protein that in humans is encoded by the UQCC3 gene. Located in mitochondria, this protein is involved in the assembly of mitochondrial Complex III, stabilizing supercomplexes containing Complex III. Mutations in the UQCC3 gene cause Complex III deficiency with symptoms of hypoglycemia, hypotonia, lactic acidosis, and developmental delays. This protein plays an important role as an antiviral factor, bolstering the ability of cells to inhibit viral replication, independent of interferon production. The UQCC3 protein can be cleaved by OMA1 metalloprotease during mitochondrial depolarization, targeting the cell for apoptosis. Depletion of this protein alters cardiolipin composition, causing cellular and mitochondrial defects. # Structure The UQCC3 gene is located on the q arm of chromosome 11 in position 12.3 and spans 2,036 base pairs. The gene produces a 10.1 kDa protein composed of 93 amino acids. This protein faces the intermembrane space. It possesses an N-terminal signal peptide and a signal transmembrane structure, in addition to several phosphorylation sites. The secondary structure of this protein is made up mostly of random coils and alpha helices. Alpha helices 2 and 3 bind to cardiolipin. # Function The UQCC3 gene encodes a protein that functions in complex III assembly, downstream of assembly factors UQCC1 and UQCC2. This is evidenced by the observation that UQCC3 levels are reduced in cells with decreased levels of UQCC1 and UQCC2, but lack of the UQCC3 protein does not affect levels of UQCC1 and UQCC2. Predicted to be a secretary protein with small molecular weight, this protein has important functions in cellular proliferation and antiviral innate immune regulation. Expression of this protein is ubiquitous in carcinomas, along with normal tissues. During the early stages of Complex III assembly, the UQCC3 protein stabilizes supercomplexes containing Complex III, most notably the III2/IV supercomplex. # Clinical Significance In the sole recorded case of a mutation in the UQCC3 gene, a patient with a homozygous missense mutation presented with nuclear type 9 complex III deficiency, displaying symptoms of hypoglycemia, hypotonia, lactic acidosis, severe delayed psychomotor development, and other developmental delay. The patient also had decreased levels of cytochrome b within Complex III. The UQCC3 protein also has a role as an antiviral factor, independent of interferon production. Levels of this protein increase in response to a viral infection, improving the ability of cells to inhibit viral replication. Overexpression of the UQCC3 gene increases transcription of OAS3 while knockdown of RNase L or OAS3 hampers the antiviral effect of UQCC3. Signaling from UQCC3 to the OAS-RNase L system is independent of interferon production. This protein is also regulated by expression of the double-stranded RNA-dependent protein kinase EIF2AK2. Depleted levels of the UQCC3 protein cause impaired respiration and subtle yet significant alterations in cardiolipin composition, which then result in abnormal crista morphology, increased sensitivity to apoptosis, and decreased levels of ATP. Furthermore, mitochondrial depolarization causes OMA1 metalloprotease to cleave the UQCC3 protein; effectively, this mechanism targets cells with damaged mitochondria for apoptosis. # Interactions This protein associates with the rest of mitochondrial Complex III and has protein-protein interactions with PHLDA3.	UQCC3 Ubiquinol-cytochrome c reductase complex assembly factor 3 is a protein that in humans is encoded by the UQCC3 gene.[1] Located in mitochondria, this protein is involved in the assembly of mitochondrial Complex III, stabilizing supercomplexes containing Complex III.[2] Mutations in the UQCC3 gene cause Complex III deficiency with symptoms of hypoglycemia, hypotonia, lactic acidosis, and developmental delays.[3] This protein plays an important role as an antiviral factor, bolstering the ability of cells to inhibit viral replication, independent of interferon production.[4] The UQCC3 protein can be cleaved by OMA1 metalloprotease during mitochondrial depolarization, targeting the cell for apoptosis. Depletion of this protein alters cardiolipin composition, causing cellular and mitochondrial defects.[2] # Structure The UQCC3 gene is located on the q arm of chromosome 11 in position 12.3 and spans 2,036 base pairs.[1] The gene produces a 10.1 kDa protein composed of 93 amino acids.[5][6] This protein faces the intermembrane space.[2] It possesses an N-terminal signal peptide and a signal transmembrane structure, in addition to several phosphorylation sites. The secondary structure of this protein is made up mostly of random coils and alpha helices.[7] Alpha helices 2 and 3 bind to cardiolipin.[2] # Function The UQCC3 gene encodes a protein that functions in complex III assembly, downstream of assembly factors UQCC1 and UQCC2. This is evidenced by the observation that UQCC3 levels are reduced in cells with decreased levels of UQCC1 and UQCC2, but lack of the UQCC3 protein does not affect levels of UQCC1 and UQCC2.[3] Predicted to be a secretary protein with small molecular weight, this protein has important functions in cellular proliferation and antiviral innate immune regulation. Expression of this protein is ubiquitous in carcinomas, along with normal tissues.[7] During the early stages of Complex III assembly, the UQCC3 protein stabilizes supercomplexes containing Complex III, most notably the III2/IV supercomplex. # Clinical Significance In the sole recorded case of a mutation in the UQCC3 gene, a patient with a homozygous missense mutation presented with nuclear type 9 complex III deficiency, displaying symptoms of hypoglycemia, hypotonia, lactic acidosis, severe delayed psychomotor development, and other developmental delay. The patient also had decreased levels of cytochrome b within Complex III.[3] The UQCC3 protein also has a role as an antiviral factor, independent of interferon production. Levels of this protein increase in response to a viral infection, improving the ability of cells to inhibit viral replication. Overexpression of the UQCC3 gene increases transcription of OAS3 while knockdown of RNase L or OAS3 hampers the antiviral effect of UQCC3. Signaling from UQCC3 to the OAS-RNase L system is independent of interferon production.[4] This protein is also regulated by expression of the double-stranded RNA-dependent protein kinase EIF2AK2.[7] Depleted levels of the UQCC3 protein cause impaired respiration and subtle yet significant alterations in cardiolipin composition, which then result in abnormal crista morphology, increased sensitivity to apoptosis, and decreased levels of ATP. Furthermore, mitochondrial depolarization causes OMA1 metalloprotease to cleave the UQCC3 protein; effectively, this mechanism targets cells with damaged mitochondria for apoptosis.[2] # Interactions This protein associates with the rest of mitochondrial Complex III and has protein-protein interactions with PHLDA3.[8]	https://www.wikidoc.org/index.php/UQCC3
fcbe6907de935f176b28894fb8b77c6d3fd969eb	wikidoc	UQCRB	UQCRB Ubiquinol-cytochrome c reductase binding protein, also known as UQCRB, Complex III subunit 7, QP-C, or Ubiquinol-cytochrome c reductase complex 14 kDa protein is a protein which in humans is encoded by the UQCRB gene.This gene encodes a subunit of the ubiquinol-cytochrome c oxidoreductase complex, which consists of one mitochondrial-encoded and 10 nuclear-encoded subunits. Mutations in this gene are associated with mitochondrial complex III deficiency. Alternatively spliced transcript variants have been found for this gene. Related pseudogenes have been identified on chromosomes 1, 5 and X. # Structure UQCRB is located on the q arm of chromosome 8 in position 22.1, has 18 exons, and spans 8,958 base pairs. The UQCRB gene produces a 5.9 kDa protein composed of 161 amino acids. The gene product of UQCRB is a subunit of the respiratory chain protein Ubiquinol Cytochrome c Reductase (UQCR, Complex III or Cytochrome bc1 complex; E.C. 1.10.2.2), which consists of the products of one mitochondrially encoded gene, MTCYTB (mitochondrial cytochrome b) and ten nuclear genes: UQCRC1, UQCRC2, Cytochrome c1, UQCRFS1 (Rieske protein), UQCRB, "14kDa protein", UQCRH (cyt c1 Hinge protein), Rieske Protein presequence, "cyt. c1 associated protein", and "Rieske-associated protein". After processing, the cleaved leader sequence of the iron-sulfur protein is retained as subunit 9, giving 11 subunits from 10 genes. # Function The ubiquinone-binding protein is a nucleus-encoded component of ubiquinol-cytochrome c oxidoreductase (Complex III) in the mitochondrial respiratory chain and plays an important role in electron transfer as a complex of ubiquinone and QP-C. The protein encoded by this gene binds ubiquinone and participates in the transfer of electrons when ubiquinone is bound. It is a target of a protein named natural anti-angiogenic small molecule terpestacin, which enables the role of the ubiquinone-binding protein as cellular oxygen sensors and participants in angiogenesis. This angiogenesis, which is the development of new blood vessels, is hypoxia induced and is facilitated by signaling mediated by ROS (mitochondrial reactive oxygen) species. In addition, UQCRB keeps maintenance of complex III. # Clinical significance Mutations in UQCRB can result in mitochondrial deficiencies and associated disorders. It is majorly associated with a complex III deficiency, a deficiency in an enzyme complex which catalyzes electron transfer from coenzyme Q to cytochrome c in the mitochondrial respiratory chain. A complex III deficiency can result in a highly variable phenotype depending on which tissues are affected. Most frequent clinical manifestations include progressive exercise intolerance and cardiomyopathy. Occasional multisystem disorders accompanied by exercise intolerance may arise as well, in forms of deafness, mental retardation, retinitis pigmentosa, cataract, growth retardation, and epilepsy. Other phenotypes include mitochondrial encephalomyopathy, mitochondrial myopathy, Leber hereditary optic neuropathy, muscle weakness, myoglobinuria, blood acidosis, renal tubulopathy, and more. Complex III deficiency is known to be rare among mitochondrial diseases. # Interactions UQCRB has binary interactions with 3 proteins, including MAGA4, Q1RN33, and 1A1L1. In addition, SDHAF2 has 69 protein-protein interactions, including COX6B1, CYC1, MYO18A, UHRF1, and others.	UQCRB Ubiquinol-cytochrome c reductase binding protein, also known as UQCRB, Complex III subunit 7, QP-C, or Ubiquinol-cytochrome c reductase complex 14 kDa protein is a protein which in humans is encoded by the UQCRB gene.This gene encodes a subunit of the ubiquinol-cytochrome c oxidoreductase complex, which consists of one mitochondrial-encoded and 10 nuclear-encoded subunits. Mutations in this gene are associated with mitochondrial complex III deficiency. Alternatively spliced transcript variants have been found for this gene. Related pseudogenes have been identified on chromosomes 1, 5 and X.[1] # Structure UQCRB is located on the q arm of chromosome 8 in position 22.1, has 18 exons, and spans 8,958 base pairs.[1] The UQCRB gene produces a 5.9 kDa protein composed of 161 amino acids.[2][3] The gene product of UQCRB is a subunit of the respiratory chain protein Ubiquinol Cytochrome c Reductase (UQCR, Complex III or Cytochrome bc1 complex; E.C. 1.10.2.2), which consists of the products of one mitochondrially encoded gene, MTCYTB (mitochondrial cytochrome b) and ten nuclear genes: UQCRC1, UQCRC2, Cytochrome c1, UQCRFS1 (Rieske protein), UQCRB, "14kDa protein", UQCRH (cyt c1 Hinge protein), Rieske Protein presequence, "cyt. c1 associated protein", and "Rieske-associated protein". After processing, the cleaved leader sequence of the iron-sulfur protein is retained as subunit 9, giving 11 subunits from 10 genes.[1] # Function The ubiquinone-binding protein is a nucleus-encoded component of ubiquinol-cytochrome c oxidoreductase (Complex III) in the mitochondrial respiratory chain and plays an important role in electron transfer as a complex of ubiquinone and QP-C. The protein encoded by this gene binds ubiquinone and participates in the transfer of electrons when ubiquinone is bound.[1] It is a target of a protein named natural anti-angiogenic small molecule terpestacin, which enables the role of the ubiquinone-binding protein as cellular oxygen sensors and participants in angiogenesis. This angiogenesis, which is the development of new blood vessels, is hypoxia induced and is facilitated by signaling mediated by ROS (mitochondrial reactive oxygen) species. In addition, UQCRB keeps maintenance of complex III.[4][5][6] # Clinical significance Mutations in UQCRB can result in mitochondrial deficiencies and associated disorders. It is majorly associated with a complex III deficiency, a deficiency in an enzyme complex which catalyzes electron transfer from coenzyme Q to cytochrome c in the mitochondrial respiratory chain. A complex III deficiency can result in a highly variable phenotype depending on which tissues are affected.[7] Most frequent clinical manifestations include progressive exercise intolerance and cardiomyopathy. Occasional multisystem disorders accompanied by exercise intolerance may arise as well, in forms of deafness, mental retardation, retinitis pigmentosa, cataract, growth retardation, and epilepsy.[7] Other phenotypes include mitochondrial encephalomyopathy, mitochondrial myopathy, Leber hereditary optic neuropathy, muscle weakness, myoglobinuria, blood acidosis, renal tubulopathy, and more.[7][8] Complex III deficiency is known to be rare among mitochondrial diseases.[8] # Interactions UQCRB has binary interactions with 3 proteins, including MAGA4, Q1RN33, and 1A1L1. In addition, SDHAF2 has 69 protein-protein interactions, including COX6B1, CYC1, MYO18A, UHRF1, and others.[9]	https://www.wikidoc.org/index.php/UQCRB
85ac7b27b9287c048ace8396e2e6b986c9c420a2	wikidoc	UQCRQ	UQCRQ Ubiquinol-cytochrome c reductase, complex III subunit VII, 9.5kDa is a protein that in humans is encoded by the UQCRQ gene. This ubiqinone-binding protein is a subunit of mitochondrial Complex III in the electron transport chain. A mutation in the UQCRQ gene has been shown to cause severe neurological disorders. Infection by Trypanosoma cruzi can cause oxidative modification of this protein in cardiac muscle tissue. # Structure The UQCRQ gene is located on the q arm of chromosome 5 in position 31.1 and spans 2,217 base pairs. The gene produces a 9.9 kDa protein composed of 82 amino acids. This protein is transmembranous, with more mass on the matrix side of the membrane. # Function This gene encodes a ubiquinone-binding protein of low molecular mass. It is a small core-associated protein and a subunit of ubiquinol-cytochrome c reductase complex III, which is part of the mitochondrial respiratory chain. # Clinical significance Variants of UQCRQ have been associated with complex III deficiency. One set of twenty consanguineous cases of a Ser45Phe mutation in the UQCRQ gene, and a different homozygous 4-bp deletion at p.338-341, have been linked to this disease. In an inbred Israeli Bedouin family, the mutations, inherited in an autosomal recessive pattern, displayed the phenotype of mitochondrial Complex III deficiency, nuclear type 4, accompanied by severe neurological symptoms. Other symptoms of complex III deficiency linked to these mutations have included hypoglycemia, lactic acidosis, and hypotonia. In another study of cardiac muscle tissue in individuals infected by Trypanosoma cruzi, an oxidative modification of the UQCRQ subunit was present, along with oxidative modification of subunits UQCRC1 and UQCRC2 of the same core complex and UQCRH and CYC1 of the neighboring subcomplex. # Interactions The protein encoded by UQCRQ has protein-protein interactions with UQCRC1, OPTN, ERCC8, GRINL1A, Dctn1, K8.1, XRCC3, PML, RAB7A, HNRNPA1L2, CDC73, NLRP3, HAUS2, TMEM248, and GOLT1B.	UQCRQ Ubiquinol-cytochrome c reductase, complex III subunit VII, 9.5kDa is a protein that in humans is encoded by the UQCRQ gene. This ubiqinone-binding protein is a subunit of mitochondrial Complex III in the electron transport chain.[1] A mutation in the UQCRQ gene has been shown to cause severe neurological disorders.[2] Infection by Trypanosoma cruzi can cause oxidative modification of this protein in cardiac muscle tissue.[3] # Structure The UQCRQ gene is located on the q arm of chromosome 5 in position 31.1 and spans 2,217 base pairs.[4] The gene produces a 9.9 kDa protein composed of 82 amino acids.[5][6] This protein is transmembranous, with more mass on the matrix side of the membrane.[7] # Function This gene encodes a ubiquinone-binding protein of low molecular mass. It is a small core-associated protein and a subunit of ubiquinol-cytochrome c reductase complex III, which is part of the mitochondrial respiratory chain.[1] # Clinical significance Variants of UQCRQ have been associated with complex III deficiency. One set of twenty consanguineous cases of a Ser45Phe mutation in the UQCRQ gene, and a different homozygous 4-bp deletion at p.338-341, have been linked to this disease. In an inbred Israeli Bedouin family, the mutations, inherited in an autosomal recessive pattern, displayed the phenotype of mitochondrial Complex III deficiency, nuclear type 4, accompanied by severe neurological symptoms.[2] Other symptoms of complex III deficiency linked to these mutations have included hypoglycemia, lactic acidosis, and hypotonia.[8] In another study of cardiac muscle tissue in individuals infected by Trypanosoma cruzi, an oxidative modification of the UQCRQ subunit was present, along with oxidative modification of subunits UQCRC1 and UQCRC2 of the same core complex and UQCRH and CYC1 of the neighboring subcomplex.[3] # Interactions The protein encoded by UQCRQ has protein-protein interactions with UQCRC1, OPTN, ERCC8, GRINL1A, Dctn1, K8.1, XRCC3, PML, RAB7A, HNRNPA1L2, CDC73, NLRP3, HAUS2, TMEM248, and GOLT1B.[9]	https://www.wikidoc.org/index.php/UQCRQ
2e13dc44ab9566fa802c691c41637cbe810444da	wikidoc	USP11	USP11 Ubiquitin carboxyl-terminal hydrolase or Ubiquitin specific protease 11 is an enzyme that in humans is encoded by the USP11 gene. USP11 belongs to the Ubiquitin specific proteases family (USPs) which is a sub-family of the Deubiquitinating enzymes (DUBs).USPs are multiple domain proteases and belong to the C19 cysteine proteases sub‒family. Depending on their domain architecture and position there is different homology between the various members. Generally the largest domain is the catalytic domain which harbours the three residue catalytic triad that is included inside conserved motifs (Cys and His boxes). The catalytic domain also contains sequences that are not related with the catalysis function and their role is mostly not clearly understood at present, the length of these sequences varies for each USP and therefore the length of the whole catalytic domain can range from approximately 295 to 850 amino acids. Particular sequences inside the catalytic domain or at the N‒terminus of some USPs have been characterised as UBL (Ubiquitin like) and DUSP (domain present in ubiquitin‒specific proteases) domains respectively. In some cases, regarding the UBL domains, it has been reported to have a catalysis enhancing function as in the case of USP7. In addition, a so‒called DU domain module is the combination of a DUSP domain followed by a UBL domain separated by a linker and is found in USP11 as well as in USP15 and USP4. USP11 is 963aa protein with a MW of approximately 109.8 kDa and a pI of ~5.28; it shares significant homology with USP15 and along with USP4 forms the DU subfamily. Nevertheless, alignment of the three USPs confirms that USP15 and USP4 are the closest homologues with the identity reaching ~73 % between their UBL1 domains whereas USP11 is the most distant member with an identity of only ~32.3 % when compared to USP15. An UBL2 domain insertion (285aa) is present within the catalytic domain, which encompasses amino acids 310‒931, and the catalytic triad consists of a cysteine, a histidine and an aspartic acid. # Function Protein ubiquitination controls many intracellular processes, including cell cycle progression, transcriptional activation, and signal transduction. This dynamic process, involving ubiquitin conjugating enzymes and deubiquitinating enzymes, adds and removes ubiquitin. Deubiquitinating enzymes are cysteine proteases that specifically cleave ubiquitin from ubiquitin-conjugated protein substrates. This gene encodes a deubiquitinating enzyme which lies in a gene cluster on chromosome Xp11.23 # Interactions USP11 has been shown to interact with RANBP9. # Model organisms Model organisms have been used in the study of USP11 function. A conditional knockout mouse line called Usp11tm1(KOMP)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	USP11 Ubiquitin carboxyl-terminal hydrolase or Ubiquitin specific protease 11 is an enzyme that in humans is encoded by the USP11 gene.[1][2] USP11 belongs to the Ubiquitin specific proteases family (USPs) which is a sub-family of the Deubiquitinating enzymes (DUBs).USPs are multiple domain proteases and belong to the C19 cysteine proteases sub‒family. Depending on their domain architecture and position there is different homology between the various members. Generally the largest domain is the catalytic domain which harbours the three residue catalytic triad that is included inside conserved motifs (Cys and His boxes). The catalytic domain also contains sequences that are not related with the catalysis function and their role is mostly not clearly understood at present, the length of these sequences varies for each USP and therefore the length of the whole catalytic domain can range from approximately 295 to 850 amino acids.[3] Particular sequences inside the catalytic domain or at the N‒terminus of some USPs have been characterised as UBL (Ubiquitin like) and DUSP (domain present in ubiquitin‒specific proteases) domains respectively. In some cases, regarding the UBL domains, it has been reported to have a catalysis enhancing function as in the case of USP7.[4] In addition, a so‒called DU domain module is the combination of a DUSP domain followed by a UBL domain separated by a linker and is found in USP11 as well as in USP15 and USP4. USP11 is 963aa protein with a MW of approximately 109.8 kDa and a pI of ~5.28; it shares significant homology with USP15 and along with USP4 forms the DU subfamily. Nevertheless, alignment of the three USPs confirms that USP15 and USP4 are the closest homologues with the identity reaching ~73 % between their UBL1 domains whereas USP11 is the most distant member with an identity of only ~32.3 % when compared to USP15. An UBL2 domain insertion (285aa) is present within the catalytic domain, which encompasses amino acids 310‒931, and the catalytic triad consists of a cysteine, a histidine and an aspartic acid. # Function Protein ubiquitination controls many intracellular processes, including cell cycle progression, transcriptional activation, and signal transduction. This dynamic process, involving ubiquitin conjugating enzymes and deubiquitinating enzymes, adds and removes ubiquitin. Deubiquitinating enzymes are cysteine proteases that specifically cleave ubiquitin from ubiquitin-conjugated protein substrates. This gene encodes a deubiquitinating enzyme which lies in a gene cluster on chromosome Xp11.23[2] # Interactions USP11 has been shown to interact with RANBP9.[5] # Model organisms Model organisms have been used in the study of USP11 function. A conditional knockout mouse line called Usp11tm1(KOMP)Wtsi was generated at the Wellcome Trust Sanger Institute.[6] Male and female animals underwent a standardized phenotypic screen[7] to determine the effects of deletion.[8][9][10][11] Additional screens performed: In-depth immunological phenotyping[12]	https://www.wikidoc.org/index.php/USP11
05c1e0627d5395f35da22d0bde3a5e33baf9edfb	wikidoc	USP20	USP20 Ubiquitin carboxyl-terminal hydrolase 20 is an enzyme that in humans is encoded by the USP20 gene. Ubiquitin-specific protease 20 (USP20), also known as ubiquitin-binding protein 20 and VHL protein-interacting deubiquitinating enzyme 2 (VDU2), is a cysteine protease deubiquitinating enzyme (DUB). The catalytic site of USP20, like other DUBs, contains conserved cysteine and histidine residues that catalyse the proteolysis of an isopeptide bond between a lysine residue of a target protein and a glycine residue of a ubiquitin molecule. USP20 is known to deubiquitinate a number of proteins including thyronine deiodinase type 2 (D2), Hypoxia-inducible factor 1α (HIF1α), and β2 adrenergic receptor (β2AR). # Gene The USP20 gene is located on chromosome 9 at the locus 9q34.11. # Structure USP20 is a 914-amino acid protein that shows 59% homology with another DUB, USP33. It contains 4 known domains, an N-terminal Zf UBP domain, a catalytic domain containing conserved histidine and cysteine residues, and two C-terminal DUSP domains. # Function DUBs are categorised into 5 main groups, ubiquitin-specific proteases (USP), ubiquitin c-terminal hydrolases (UCH), ovarian tumour proteases (OTU), Machado-Joseph disease proteases (MJD), and JAB1/MPN/MOV34 proteases (JAMM/MPN+). The first four groups are cysteine proteases, whereas the last group are Zn metalloproteases. USP20 belongs to the USP group and, like most DUBs, catalyse the breakage of an isopeptide bond between a lysine residue of the target protein and the terminal glycine residue of a ubiquitin protein. This occurs via a conserved cysteine and histidine residue in the catalytic site of the enzyme. The histidine molecule is protonated by the cysteine residue and this allows the cystein residue to undergo a nucleophillic attack on the isopeptide bond, which removes the ubiquitin from the substrate protein. ## Thyronine deiodinase type 2 USP20 deubiquitinates thyronine deiodinase type 2 (D2), an enzyme that converts thyroxine (T4) into active 3,5,3'-triiodothyronine (T3). D2 is ubiquitinated after binding of T4, which signals for the degradation of D2 via the proteasome and also causes an inactivating conformational change of the protein. Deubiquitination by USP20 rescues D2 from degradation and also returns D2 to its active conformation. ## Hypoxia inducible factor 1α The von Hippel-Lindau tumour suppressor protein (pVHL) ubiquitinates hypoxia-inducible factor 1α (HIF1α) when cell oxygen levels are normal. This leads to the degradation of HIF1α and prevents the transcription of hypoxic response genes such as vascular endothelial growth factor, platelet-derived growth factor B, and erythropoietin. USP20 deubiquitinates HIF1α, preventing its proteasomal degradation, and allows it to transcribe the hypoxic response genes. ## β2 adrenergic receptor USP20 is involved in the recycling of the β2-adrenergic receptor. After agonist stimulation, the receptor is internalised and ubiquitinated. USP20 serves to deubiquitinate the receptor and prevent its degradation by the proteasome. This allows it to be recycled to the cell surface in order to resensitize the cell to signalling molecules. # Regulation In addition to the regulation of HIF1α, pVHL regulates USP20. USP20 binds to the β-domain of pVHL and is subsequently ubiquitinated. This signals USP20 for degradation via the proteasome. # Model organisms Model organisms have been used in the study of USP20 function. A conditional knockout mouse line called Usp20tm1a(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	USP20 Ubiquitin carboxyl-terminal hydrolase 20 is an enzyme that in humans is encoded by the USP20 gene.[1][2] Ubiquitin-specific protease 20 (USP20), also known as ubiquitin-binding protein 20 and VHL protein-interacting deubiquitinating enzyme 2 (VDU2), is a cysteine protease deubiquitinating enzyme (DUB). The catalytic site of USP20, like other DUBs, contains conserved cysteine and histidine residues that catalyse the proteolysis of an isopeptide bond between a lysine residue of a target protein and a glycine residue of a ubiquitin molecule.[3] USP20 is known to deubiquitinate a number of proteins including thyronine deiodinase type 2 (D2), Hypoxia-inducible factor 1α (HIF1α), and β2 adrenergic receptor (β2AR).[4][5][6] # Gene The USP20 gene is located on chromosome 9 at the locus 9q34.11.[2][7] # Structure USP20 is a 914-amino acid protein that shows 59% homology with another DUB, USP33.[8] It contains 4 known domains, an N-terminal Zf UBP domain, a catalytic domain containing conserved histidine and cysteine residues, and two C-terminal DUSP domains.[9] # Function DUBs are categorised into 5 main groups, ubiquitin-specific proteases (USP), ubiquitin c-terminal hydrolases (UCH), ovarian tumour proteases (OTU), Machado-Joseph disease proteases (MJD), and JAB1/MPN/MOV34 proteases (JAMM/MPN+). The first four groups are cysteine proteases, whereas the last group are Zn metalloproteases. USP20 belongs to the USP group and, like most DUBs, catalyse the breakage of an isopeptide bond between a lysine residue of the target protein and the terminal glycine residue of a ubiquitin protein. This occurs via a conserved cysteine and histidine residue in the catalytic site of the enzyme. The histidine molecule is protonated by the cysteine residue and this allows the cystein residue to undergo a nucleophillic attack on the isopeptide bond, which removes the ubiquitin from the substrate protein.[10] ## Thyronine deiodinase type 2 USP20 deubiquitinates thyronine deiodinase type 2 (D2), an enzyme that converts thyroxine (T4) into active 3,5,3'-triiodothyronine (T3). D2 is ubiquitinated after binding of T4, which signals for the degradation of D2 via the proteasome and also causes an inactivating conformational change of the protein. Deubiquitination by USP20 rescues D2 from degradation and also returns D2 to its active conformation.[4][11] ## Hypoxia inducible factor 1α The von Hippel-Lindau tumour suppressor protein (pVHL) ubiquitinates hypoxia-inducible factor 1α (HIF1α) when cell oxygen levels are normal. This leads to the degradation of HIF1α and prevents the transcription of hypoxic response genes such as vascular endothelial growth factor, platelet-derived growth factor B, and erythropoietin. USP20 deubiquitinates HIF1α, preventing its proteasomal degradation, and allows it to transcribe the hypoxic response genes.[12] ## β2 adrenergic receptor USP20 is involved in the recycling of the β2-adrenergic receptor. After agonist stimulation, the receptor is internalised and ubiquitinated. USP20 serves to deubiquitinate the receptor and prevent its degradation by the proteasome. This allows it to be recycled to the cell surface in order to resensitize the cell to signalling molecules.[6] # Regulation In addition to the regulation of HIF1α, pVHL regulates USP20. USP20 binds to the β-domain of pVHL and is subsequently ubiquitinated. This signals USP20 for degradation via the proteasome.[8] # Model organisms Model organisms have been used in the study of USP20 function. A conditional knockout mouse line called Usp20tm1a(EUCOMM)Hmgu was generated at the Wellcome Trust Sanger Institute.[13] Male and female animals underwent a standardized phenotypic screen[14] to determine the effects of deletion.[15][16][17][18] Additional screens performed: - In-depth immunological phenotyping[19]	https://www.wikidoc.org/index.php/USP20
ae0d19c08d7915fa7cb9cc57e27e78f3817bcf01	wikidoc	USP48	USP48 Ubiquitin carboxyl-terminal hydrolase 48 is an enzyme that in humans is encoded by the USP48 gene. This gene encodes a protein containing domains that associate it with the peptidase family C19, also known as family 2 of ubiquitin carboxyl-terminal hydrolases. Family members function as deubiquitinating enzymes, recognizing and hydrolyzing the peptide bond at the C-terminal glycine of ubiquitin. Enzymes in peptidase family C19 are involved in the processing of poly-ubiquitin precursors as well as that of ubiquitinated proteins. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. In melanocytic cells USP48 gene expression may be regulated by MITF.	USP48 Ubiquitin carboxyl-terminal hydrolase 48 is an enzyme that in humans is encoded by the USP48 gene.[1][2] This gene encodes a protein containing domains that associate it with the peptidase family C19, also known as family 2 of ubiquitin carboxyl-terminal hydrolases. Family members function as deubiquitinating enzymes, recognizing and hydrolyzing the peptide bond at the C-terminal glycine of ubiquitin. Enzymes in peptidase family C19 are involved in the processing of poly-ubiquitin precursors as well as that of ubiquitinated proteins. Alternate transcriptional splice variants, encoding different isoforms, have been characterized.[2] In melanocytic cells USP48 gene expression may be regulated by MITF.[3]	https://www.wikidoc.org/index.php/USP48
0b8621be58eed517a58d9346a3f7ea48a234fd50	wikidoc	USP53	USP53 Inactive ubiquitin carboxyl-terminal hydrolase 53 is a protein that in humans is encoded by the USP53 gene. Although USP53 is classified as a deubiquitinating enzyme based on sequence homology to other proteases from this group, it lacks a functionally essential histydine in the catalytic domaine and activity assays suggest that USP53 is catalytically inactive. Even though USP53 is devoid of catalytic activity, USP53 serves important physiological functions: mutations in Usp53 have been shown to cause progressive hearing loss in mice, as well as late-onset hearing loss and cholestasis in humans. USP53 localizes at cellular tight junctions and interacts with tight junction protein 2 (TJP2). Mutations in TJP2 have also been shown to cause hearing impairments and cholestasis.	USP53 Inactive ubiquitin carboxyl-terminal hydrolase 53 is a protein that in humans is encoded by the USP53 gene.[1] Although USP53 is classified as a deubiquitinating enzyme based on sequence homology to other proteases from this group, it lacks a functionally essential histydine in the catalytic domaine and activity assays suggest that USP53 is catalytically inactive. [2][3][4] Even though USP53 is devoid of catalytic activity, USP53 serves important physiological functions: mutations in Usp53 have been shown to cause progressive hearing loss in mice,[4] as well as late-onset hearing loss and cholestasis in humans.[5] USP53 localizes at cellular tight junctions and interacts with tight junction protein 2 (TJP2).[4] Mutations in TJP2 have also been shown to cause hearing impairments [6] and cholestasis.[7]	https://www.wikidoc.org/index.php/USP53
9793977a98802aa31b21c62944e81890cdf04c1a	wikidoc	USP9X	USP9X Probable ubiquitin carboxyl-terminal hydrolase FAF-X is an enzyme that in humans is encoded by the USP9X gene. # Function This gene is a member of the peptidase C19 family and encodes a protein that is similar to ubiquitin-specific proteases. Though this gene is located on the X chromosome, it escapes X-inactivation. Depletion of USP9X from two-cell mouse embryos halts blastocyst development and results in slower blastomere cleavage rate, impaired cell adhesion and a loss of cell polarity. It has also been implicated that USP9X is likely to influence developmental processes through signaling pathways of Notch, Wnt, EGF, and mTOR. USP9X has been recognized in studies of mouse and human stem cells involving embryonic, neural and hematopoietic stem cells. High expression is retained in undifferentiated progenitor and stem cells and decreases as differentiation continues. USP9X is a protein-coding gene that has been implicated either directly through mutations or indirectly in a number of neurodevelopmental and neurodegenerative disorders. Three mutations have been connected with X-linked intellectual disability and disrupt neuronal growth and cell migration. Neurodegenerative disorders, such as Alzheimer's, Parkinson's and Huntington's disease, have also been linked to USP9X. Specifically, USP9X has been implicated in the regulation of the phosphorylation and expression of the microtule-associated protein tau, which forms pathological aggregates in Alzheimer's and other tauopathies. Scientists have generated a knockout model where they isolated hippocampal neurons from an USP9X-knockout male mouse, which showed a 43% reduction in axonal length and aborization compared to wildtype. # Interactions USP9X has been shown to interact with: - Beta-catenin, - MARK4, - MLLT4, and - NUAK1. - ERG. - CEP131	USP9X Probable ubiquitin carboxyl-terminal hydrolase FAF-X is an enzyme that in humans is encoded by the USP9X gene.[1][2] # Function This gene is a member of the peptidase C19 family and encodes a protein that is similar to ubiquitin-specific proteases. Though this gene is located on the X chromosome, it escapes X-inactivation. Depletion of USP9X from two-cell mouse embryos halts blastocyst development and results in slower blastomere cleavage rate, impaired cell adhesion and a loss of cell polarity. It has also been implicated that USP9X is likely to influence developmental processes through signaling pathways of Notch, Wnt, EGF, and mTOR. USP9X has been recognized in studies of mouse and human stem cells involving embryonic, neural and hematopoietic stem cells.[3] High expression is retained in undifferentiated progenitor and stem cells and decreases as differentiation continues. USP9X is a protein-coding gene that has been implicated either directly through mutations or indirectly in a number of neurodevelopmental and neurodegenerative disorders. Three mutations have been connected with X-linked intellectual disability and disrupt neuronal growth and cell migration. Neurodegenerative disorders, such as Alzheimer's, Parkinson's and Huntington's disease, have also been linked to USP9X. Specifically, USP9X has been implicated in the regulation of the phosphorylation and expression of the microtule-associated protein tau, which forms pathological aggregates in Alzheimer's and other tauopathies.[4] Scientists have generated a knockout model where they isolated hippocampal neurons from an USP9X-knockout male mouse, which showed a 43% reduction in axonal length and aborization compared to wildtype.[5] # Interactions USP9X has been shown to interact with: - Beta-catenin,[6] - MARK4,[7] - MLLT4,[6][8] and - NUAK1.[7] - ERG.[9] - CEP131[10]	https://www.wikidoc.org/index.php/USP9X
28a61e06a35b78a6beb2dda4c9fc266e75c18b5b	wikidoc	USP9Y	USP9Y Ubiquitin specific peptidase 9, Y-linked (fat facets-like, Drosophila), also known as USP9Y, is an enzyme which in humans is encoded by the USP9Y gene. It is required for sperm production. This enzyme is a member of the peptidase C19 family and is similar to ubiquitin-specific proteases, which cleave the ubiquitin moiety from ubiquitin-fused precursors and ubiquitinylated proteins. # Clinical significance Mutations in this gene have been associated with Sertoli cell-only syndrome (SCO) and male infertility. The USP9Y gene is found on the azoospermia factor (AZF) region on the Y chromosome. Men who have impaired or no sperm production often have a deletion in the AZF region, especially in the USP9Y gene, and it was thought that USP9Y was necessary for sperm production. However, a man and his father with a USP9Y deletion who could produce sperm were recently reported. The corresponding gene is present but inactive in chimpanzees and bonobos.	USP9Y Ubiquitin specific peptidase 9, Y-linked (fat facets-like, Drosophila), also known as USP9Y, is an enzyme which in humans is encoded by the USP9Y gene.[1] It is required for sperm production. This enzyme is a member of the peptidase C19 family and is similar to ubiquitin-specific proteases, which cleave the ubiquitin moiety from ubiquitin-fused precursors and ubiquitinylated proteins. # Clinical significance Mutations in this gene have been associated with Sertoli cell-only syndrome (SCO) and male infertility.[1] The USP9Y gene is found on the azoospermia factor (AZF) region on the Y chromosome. Men who have impaired or no sperm production often have a deletion in the AZF region, especially in the USP9Y gene, and it was thought that USP9Y was necessary for sperm production. However, a man and his father with a USP9Y deletion who could produce sperm were recently reported. The corresponding gene is present but inactive in chimpanzees and bonobos.[2][3]	https://www.wikidoc.org/index.php/USP9Y
e66fbac4246a1f809f1d1d5d3641d4108d1f13d7	wikidoc	USPTO	USPTO # Overview The United States Patent and Trademark Office (PTO or USPTO) is an agency in the United States Department of Commerce that issues patents to inventors and businesses for their inventions, and trademark registration for product and intellectual property identification. The USPTO is currently based in Alexandria, Virginia, after a 2006 move from the Crystal City, Virginia area of Arlington County, Virginia. A few offices remain in the Potomac Gateway complex at the southern end of Crystal City; these offices will move to Randolph Square, a brand new building in Shirlington Village, in 2009. Since 1991, the office has been fully funded by fees charged for processing patents and trademarks. The USPTO cooperates with the European Patent Office (EPO) and the Japan Patent Office (JPO) as one of the Trilateral Patent Offices. The USPTO is also a Receiving Office, an International Searching Authority and an International Preliminary Examination Authority for international patent applications filed in accordance with the Patent Cooperation Treaty. # Mission The mission of the PTO is to promote "industrial and technological progress in the United States and strengthen the national economy" by: - administering the laws relating to patents and trademarks; - advising the United States Secretary of Commerce, the President of the United States, and the administration on patent, trademark, and copyright protection; and - providing advice on the trade-related aspects of intellectual property.	USPTO Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] # Overview The United States Patent and Trademark Office (PTO or USPTO) is an agency in the United States Department of Commerce that issues patents to inventors and businesses for their inventions, and trademark registration for product and intellectual property identification. The USPTO is currently based in Alexandria, Virginia, after a 2006 move from the Crystal City, Virginia area of Arlington County, Virginia. A few offices remain in the Potomac Gateway complex at the southern end of Crystal City; these offices will move to Randolph Square, a brand new building in Shirlington Village, in 2009. Since 1991, the office has been fully funded by fees charged for processing patents and trademarks. The USPTO cooperates with the European Patent Office (EPO) and the Japan Patent Office (JPO) as one of the Trilateral Patent Offices. The USPTO is also a Receiving Office, an International Searching Authority and an International Preliminary Examination Authority for international patent applications filed in accordance with the Patent Cooperation Treaty. # Mission The mission of the PTO is to promote "industrial and technological progress in the United States and strengthen the national economy" by: - administering the laws relating to patents and trademarks; - advising the United States Secretary of Commerce, the President of the United States, and the administration on patent, trademark, and copyright protection; and - providing advice on the trade-related aspects of intellectual property.	https://www.wikidoc.org/index.php/USPTO
c8f812bad1d2a54356aa65bc2944c774616aae0d	wikidoc	Ulcer	Ulcer Synonyms and keywords: ulceration An ulcer is a discontinuity or break in a bodily membrane that impedes the organ of which that membrane is a part from continuing its normal functions. Common forms of ulcers recognized in medicine include: - Ulcer (dermatology), a discontinuity of the skin or a break in the skin - Pressure ulcers, also known as bedsores - Genital ulcer, an ulcer located on the genital area - Ulcerative dermatitis, a skin disorder associated with bacterial growth often initiated by self-trauma - Corneal ulcer, an inflammatory or infective condition of the cornea - Coronary artery ulceration, defined as a cavity in the vessel wall with disruption of the intima and flow observed within the plaque cavity - Mouth ulcer, an open sore inside the mouth - Aphthous ulcer, a specific type of oral ulcer also known as a canker sore - Peptic ulcer, a discontinuity of the gastrointestinal mucosa (stomach ulcer) - Venous ulcer, a wound thought to occur due to improper functioning of valves in the veins - Stress ulcer, located anywhere within the stomach and proximal duodenum - Ulcerative sarcoidosis, a cutaneous condition affecting people with sarcoidosis - Ulcerative lichen planus, a rare variant of lichen planus - Ulcerative colitis, a form of inflammatory bowel disease (IBD) - Ulcerative disposition, a disorder or discomfort that causes severe abdominal distress, often associated with chronic gastritis - Medication: diclofenac (patch)	Ulcer Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Synonyms and keywords: ulceration An ulcer is a discontinuity or break in a bodily membrane that impedes the organ of which that membrane is a part from continuing its normal functions. Common forms of ulcers recognized in medicine include: - Ulcer (dermatology), a discontinuity of the skin or a break in the skin - Pressure ulcers, also known as bedsores - Genital ulcer, an ulcer located on the genital area - Ulcerative dermatitis, a skin disorder associated with bacterial growth often initiated by self-trauma - Corneal ulcer, an inflammatory or infective condition of the cornea - Coronary artery ulceration, defined as a cavity in the vessel wall with disruption of the intima and flow observed within the plaque cavity - Mouth ulcer, an open sore inside the mouth - Aphthous ulcer, a specific type of oral ulcer also known as a canker sore - Peptic ulcer, a discontinuity of the gastrointestinal mucosa (stomach ulcer) - Venous ulcer, a wound thought to occur due to improper functioning of valves in the veins - Stress ulcer, located anywhere within the stomach and proximal duodenum - Ulcerative sarcoidosis, a cutaneous condition affecting people with sarcoidosis - Ulcerative lichen planus, a rare variant of lichen planus - Ulcerative colitis, a form of inflammatory bowel disease (IBD) - Ulcerative disposition, a disorder or discomfort that causes severe abdominal distress, often associated with chronic gastritis - Medication: diclofenac (patch)	https://www.wikidoc.org/index.php/Ulcer
83cb2b794fe16ef1396fe6b1d78af97fcf71ce50	wikidoc	Umami	Umami Glutamate has a long history in cooking: it appears in Asian foods such as soy sauce and fish sauce, and in Italian food in parmesan cheese and anchovies. It is the taste of Marmite in the UK, of Golden Mountain sauce in Thailand, of Maggi Sauce worldwide, of Goya Sazón on the Latin islands of the Caribbean, of Salsa Lizano in Costa Rica and of Kewpie mayonnaise in Japan. It also is directly available in monosodium glutamate. Inasmuch as it describes the flavor common to savory products such as meat, cheese, and mushrooms, umami is similar to Brillat-Savarin's concept of osmazome (link in French), an early attempt to describe the main flavoring component of meat as extracted in the process of making stock. # Chemical properties Umami was first identified as a basic taste in 1908 by Kikunae Ikeda of the Tokyo Imperial University while researching the strong flavor in seaweed broth. Ikeda isolated monosodium glutamate as the chemical responsible and, with the help of the Ajinomoto company, began commercial distribution of MSG products. # Taste receptors Acknowledged subjectively as a special taste by Eastern civilizations for generations, umami has been described in biochemical studies identifying the actual taste receptor responsible for the sense of umami, a modified form of mGluR4 named "taste-mGluR4". Umami tastes are initiated by these specialized receptors, with subsequent steps involving secretion of neurotransmitters, including adenosine triphosphate (ATP) and serotonin. Other evidence indicates guanosine derivatives may interact with and boost the initial umami signal. Cells responding to umami taste stimuli do not possess typical synapses but instead secrete the neurotransmitter ATP in a mechanism exciting sensory fibers that convey taste signals to the brain. These taste receptors are located everywhere on the tongue. In monkey studies, most umami signals from taste buds excite neurons in the orbitofrontal cortex of the brain, showing spatially-specific characteristics: - There is a cortical map representation for the taste of glutamate separate from that of other taste stimuli like sweet (glucose), salt, bitter (quinine) and sour (hydrochloric acid) - Single neurons having vigorous responses to sodium glutamate also respond to glutamic acid - Some neurons display a mechanism of satiety, indicating a process by which taste receptors in the mouth may interact with cortical neurons to curtail eating - Umami flavor is strongest when combined with aromas (e.g., monosodium glutamate and garlic), a result leading to speculation that glutamate may stimulate umami effects by acting simultaneously with the aromas, texture and appearance of food.	Umami Template:Nihongo is a proposed addition to the currently accepted four basic tastes sensed by specialized receptor cells present on the human tongue.[1] The same taste is also known as xiānwèi (Template:Zh-ts) in Chinese cooking. Umami is a Japanese word meaning "savory" or "deliciousness" and so applies to the sensation of savoriness, specifically to the detection of the natural amino acid, glutamic acid, or glutamates common in meats, cheese and other protein-heavy foods. The action of umami receptors explains why foods treated with monosodium glutamate (MSG) often taste "heartier". Glutamate has a long history in cooking: it appears in Asian foods such as soy sauce and fish sauce, and in Italian food in parmesan cheese and anchovies. It is the taste of Marmite in the UK, of Golden Mountain sauce in Thailand, of Maggi Sauce worldwide, of Goya Sazón on the Latin islands of the Caribbean, of Salsa Lizano in Costa Rica and of Kewpie mayonnaise in Japan. It also is directly available in monosodium glutamate.[2] Inasmuch as it describes the flavor common to savory products such as meat, cheese, and mushrooms, umami is similar to Brillat-Savarin's concept of osmazome (link in French), an early attempt to describe the main flavoring component of meat as extracted in the process of making stock. # Chemical properties Umami was first identified as a basic taste in 1908 by Kikunae Ikeda of the Tokyo Imperial University while researching the strong flavor in seaweed broth.[3][4] Ikeda isolated monosodium glutamate as the chemical responsible and, with the help of the Ajinomoto company, began commercial distribution of MSG products. # Taste receptors Acknowledged subjectively as a special taste by Eastern civilizations for generations, umami has been described in biochemical studies identifying the actual taste receptor responsible for the sense of umami, a modified form of mGluR4[5] named "taste-mGluR4". Umami tastes are initiated by these specialized receptors, with subsequent steps involving secretion of neurotransmitters, including adenosine triphosphate (ATP) and serotonin.[6] Other evidence indicates guanosine derivatives may interact with and boost the initial umami signal.[7] Cells responding to umami taste stimuli do not possess typical synapses but instead secrete the neurotransmitter ATP in a mechanism exciting sensory fibers that convey taste signals to the brain. These taste receptors are located everywhere on the tongue.[citation needed] In monkey studies, most umami signals from taste buds excite neurons in the orbitofrontal cortex of the brain, showing spatially-specific characteristics:[8] - There is a cortical map representation for the taste of glutamate separate from that of other taste stimuli like sweet (glucose), salt, bitter (quinine) and sour (hydrochloric acid) - Single neurons having vigorous responses to sodium glutamate also respond to glutamic acid - Some neurons display a mechanism of satiety, indicating a process by which taste receptors in the mouth may interact with cortical neurons to curtail eating - Umami flavor is strongest when combined with aromas (e.g., monosodium glutamate and garlic), a result leading to speculation that glutamate may stimulate umami effects by acting simultaneously with the aromas, texture and appearance of food.	https://www.wikidoc.org/index.php/Umami
b6d0f84758476bd47d0f8343a12772d200b61d2b	wikidoc	VAC14	VAC14 Protein VAC14 homolog, also known as ArPIKfyve (Associated Regulator of PIKfyve), is a protein that in humans is encoded by the VAC14 gene. # Functions and interactions The content of phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5)P2) in endosomal membranes changes dynamically with fission and fusion events that generate or absorb intracellular transport vesicles. The ArPIKfyve protein scaffolds a trimolecular complex to tightly regulate the level of PtdIns(3,5)P2. Other components of this complex are the PtdIns(3,5)P2-synthesizing enzyme PIKFYVE and the Sac1-domain-containing PtdIns(3,5)P2 5-phosphatase Sac3, encoded by the human gene FIG4. VAC14 functions as an activator of PIKFYVE. Studies in VAC14 knockout mice indicate that, in addition to increasing the PtdIns(3,5)P2-producing activity of PIKfyve, VAC14 also controls the steady-state levels of another rare phosphoinositide linked to PIKfyve enzyme activity – phosphatidylinositol 5-phosphate. In addition to the formation of the ternary complex with PIKfyve and Sac3, ArPIKfyve is engaged in a number of other interactions. ArPIKfyve forms a stable complex with the PtdIns(3,5)P2-specific phosphatase Sac3, thereby protecting Sac3 from rapid degradation in the proteasome. ArPIKfyve forms a homooligomer through its carboxyl terminus. However, the number of monomers in the ArPIKfyve homooligomer, ArPIKfyve-Sac3 heterodimer or PIKfyve-ArPIKfyve-Sac3 heterotrimer is unknown. Human Vac14/ArPIKfyve also interacts with the PDZ (post-synaptic density) domain of neuronal nitric oxide synthase but the functional significance of this interaction is still unclear. ArPIKfyve facilitates insulin-regulated GLUT4 translocation to the cell surface. # Lessons from VAC14 mouse models VAC14 knock-out mice die at, or shortly after birth and exhibit massive neurodegeneration. Fibroblasts from these mice display ~50% lower levels of PtdIns(3,5)P2 and PtdIns(5)P. A spontaneous mouse VAC14-point mutation (with arginine substitution of leucine156) is associated with reduced life span (up to 3 weeks), body size, enlarged brain ventricles, 50% decrease in PtdIns(3,5)P2 levels, diluted pigmentation, tremor and impaired motor function. # VAC14 and human disease The VAC14 gene is yet to be linked convincingly to human disease.	VAC14 Protein VAC14 homolog, also known as ArPIKfyve (Associated Regulator of PIKfyve), is a protein that in humans is encoded by the VAC14 gene.[1][2][3] # Functions and interactions The content of phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5)P2) in endosomal membranes changes dynamically with fission and fusion events that generate or absorb intracellular transport vesicles. The ArPIKfyve protein scaffolds a trimolecular complex to tightly regulate the level of PtdIns(3,5)P2. Other components of this complex are the PtdIns(3,5)P2-synthesizing enzyme PIKFYVE and the Sac1-domain-containing PtdIns(3,5)P2 5-phosphatase Sac3, encoded by the human gene FIG4. VAC14 functions as an activator of PIKFYVE.[1][4] Studies in VAC14 knockout mice indicate that, in addition to increasing the PtdIns(3,5)P2-producing activity of PIKfyve, VAC14 also controls the steady-state levels of another rare phosphoinositide linked to PIKfyve enzyme activity – phosphatidylinositol 5-phosphate. In addition to the formation of the ternary complex with PIKfyve and Sac3, ArPIKfyve is engaged in a number of other interactions. ArPIKfyve forms a stable complex with the PtdIns(3,5)P2-specific phosphatase Sac3, thereby protecting Sac3 from rapid degradation in the proteasome.[5] ArPIKfyve forms a homooligomer through its carboxyl terminus. However, the number of monomers in the ArPIKfyve homooligomer, ArPIKfyve-Sac3 heterodimer or PIKfyve-ArPIKfyve-Sac3 heterotrimer is unknown.[6] Human Vac14/ArPIKfyve also interacts with the PDZ (post-synaptic density) domain of neuronal nitric oxide synthase [7] but the functional significance of this interaction is still unclear. ArPIKfyve facilitates insulin-regulated GLUT4 translocation to the cell surface.[8] # Lessons from VAC14 mouse models VAC14 knock-out mice die at, or shortly after birth and exhibit massive neurodegeneration. Fibroblasts from these mice display ~50% lower levels of PtdIns(3,5)P2 and PtdIns(5)P.[9] A spontaneous mouse VAC14-point mutation (with arginine substitution of leucine156) is associated with reduced life span (up to 3 weeks), body size, enlarged brain ventricles, 50% decrease in PtdIns(3,5)P2 levels, diluted pigmentation, tremor and impaired motor function.[10] # VAC14 and human disease The VAC14 gene is yet to be linked convincingly to human disease.[11]	https://www.wikidoc.org/index.php/VAC14
c0a189ebfecb7053612503670c6f03ea4635bfce	wikidoc	VAMP1	VAMP1 Vesicle-associated membrane protein 1 is a protein that in humans is encoded by the VAMP1 gene. # Function Synaptobrevins/VAMPs, syntaxins, and the 25-kD synaptosomal-associated protein SNAP25 are the main components of a protein complex involved in the docking and/or fusion of synaptic vesicles with the presynaptic membrane. VAMP1 is a member of the vesicle-associated membrane protein (VAMP)/synaptobrevin family. Multiple alternative splice variants that encode proteins with alternative carboxy ends have been described, but the full-length nature of some variants has not been defined. # Clinical significance Homozygous mutations in VAMP1 have been identified in a series of children affected with a form of congenital myasthenic syndrome and similar presynaptic features in these patients and the knock-out VAMP1 mouse have been demonstrated. # Interactive pathway map Click on genes, proteins and metabolites below to link to respective articles. - ↑ The interactive pathway map can be edited at WikiPathways: "NicotineDopaminergic_WP1602"..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}	VAMP1 Vesicle-associated membrane protein 1 is a protein that in humans is encoded by the VAMP1 gene.[1][2] # Function Synaptobrevins/VAMPs, syntaxins, and the 25-kD synaptosomal-associated protein SNAP25 are the main components of a protein complex involved in the docking and/or fusion of synaptic vesicles with the presynaptic membrane. VAMP1 is a member of the vesicle-associated membrane protein (VAMP)/synaptobrevin family. Multiple alternative splice variants that encode proteins with alternative carboxy ends have been described, but the full-length nature of some variants has not been defined.[2] # Clinical significance Homozygous mutations in VAMP1 have been identified in a series of children affected with a form of congenital myasthenic syndrome and similar presynaptic features in these patients and the knock-out VAMP1 mouse have been demonstrated.[3] # Interactive pathway map Click on genes, proteins and metabolites below to link to respective articles.[§ 1] - ↑ The interactive pathway map can be edited at WikiPathways: "NicotineDopaminergic_WP1602"..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/VAMP1
96dcd24876cea4c760ed151e1e6a636365f293cb	wikidoc	VAMP2	VAMP2 Vesicle-associated membrane protein 2 is a protein that in humans is encoded by the VAMP2 gene. # Function Synaptobrevins/VAMPs, syntaxins, and the 25-kD synaptosomal-associated protein SNAP25 are the main components of a protein complex involved in the docking and/or fusion of synaptic vesicles with the presynaptic membrane. VAMP2 is a member of the vesicle-associated membrane protein (VAMP)/synaptobrevin family. VAMP2 is thought to participate in neurotransmitter release at a step between docking and fusion. Mice lacking functional synaptobrevin2/VAMP2 gene cannot survive after birth, and have a dramatically reduced synaptic transmission, around 10% of control. The protein forms a stable complex with syntaxin, synaptosomal-associated protein, 25 kD, and complexin. It also forms a distinct complex with synaptophysin. # Clinical significance VAMP2 is a likely candidate gene for familial infantile myasthenia (FIMG) because of its map location and because it encodes a synaptic vesicle protein of the type that has been implicated in the pathogenesis of FIMG. # Interactions VAMP2 has been shown to interact with: - RABAC1, - SNAP-25, - SNAP23, - STX1A, and - STX4.	VAMP2 Vesicle-associated membrane protein 2 is a protein that in humans is encoded by the VAMP2 gene.[1][2] # Function Synaptobrevins/VAMPs, syntaxins, and the 25-kD synaptosomal-associated protein SNAP25 are the main components of a protein complex involved in the docking and/or fusion of synaptic vesicles with the presynaptic membrane. VAMP2 is a member of the vesicle-associated membrane protein (VAMP)/synaptobrevin family. VAMP2 is thought to participate in neurotransmitter release at a step between docking and fusion. Mice lacking functional synaptobrevin2/VAMP2 gene cannot survive after birth, and have a dramatically reduced synaptic transmission, around 10% of control.[3] The protein forms a stable complex with syntaxin, synaptosomal-associated protein, 25 kD, and complexin. It also forms a distinct complex with synaptophysin.[2] # Clinical significance VAMP2 is a likely candidate gene for familial infantile myasthenia (FIMG) because of its map location and because it encodes a synaptic vesicle protein of the type that has been implicated in the pathogenesis of FIMG. # Interactions VAMP2 has been shown to interact with: - RABAC1,[4] - SNAP-25,[5][6][7] - SNAP23,[8][9][10] - STX1A,[6][7][11][12][13][14] and - STX4.[8][15][16][17]	https://www.wikidoc.org/index.php/VAMP2
90d82f59b5e7c75015f2a061576c1787c036feb4	wikidoc	VAMP4	VAMP4 Vesicle-associated membrane protein 4 is a protein that in humans is encoded by the VAMP4 gene. # Function Synaptobrevins/VAMPs, syntaxins, and the 25-kD synaptosomal-associated protein SNAP25 are the main components of a protein complex involved in the docking and/or fusion of synaptic vesicles with the presynaptic membrane. The protein encoded by this gene is a member of the vesicle-associated membrane protein (VAMP)/synaptobrevin family. This protein may play a role in trans-Golgi network-to-endosome transport. # Interactions VAMP4 has been shown to interact with AP1M1, STX6 and STX16.	VAMP4 Vesicle-associated membrane protein 4 is a protein that in humans is encoded by the VAMP4 gene.[1][2] # Function Synaptobrevins/VAMPs, syntaxins, and the 25-kD synaptosomal-associated protein SNAP25 are the main components of a protein complex involved in the docking and/or fusion of synaptic vesicles with the presynaptic membrane. The protein encoded by this gene is a member of the vesicle-associated membrane protein (VAMP)/synaptobrevin family. This protein may play a role in trans-Golgi network-to-endosome transport.[2] # Interactions VAMP4 has been shown to interact with AP1M1,[3] STX6[4] and STX16.[4]	https://www.wikidoc.org/index.php/VAMP4
9181cf771c2660cf5b54d5386aaea67e26fa57a6	wikidoc	VDAC2	VDAC2 Voltage-dependent anion-selective channel protein 2 is a protein that in humans is encoded by the VDAC2 gene on chromosome 10. This protein is a voltage-dependent anion channel and shares high structural homology with the other VDAC isoforms. VDACs are generally involved in the regulation of cell metabolism, mitochondrial apoptosis, and spermatogenesis. Additionally, VDAC2 participates in cardiac contractions and pulmonary circulation, which implicate it in cardiopulmonary diseases. VDAC2 also mediates immune response to infectious bursal disease (IBD). # Structure The three VDAC isoforms in human are highly conserved, particularly with respect to their 3D structure. VDACs form a wide β-barrel structure, inside of which the N-terminal resides to partially close the pore. The sequence of the VDAC2 isoform contains an abundance of cysteines, which allow for the formation of disulfide bridges and, ultimately, affect the flexibility of the β-barrel. VDACs also contain a mitochondrial targeting sequence for the protein's translocation to the outer mitochondrial membrane. In particular, VDAC2 possesses an N-terminal longer by 11 residues compared to the other two isoforms. # Function VDAC2 belongs to the mitochondrial porin family and is expected to share similar biological functions to the other VDAC isoforms. VDACs generally are involved in cellular energy metabolism by transporting ATP and other small ions and metabolites across the outer mitochondrial membrane. In mammalian cardiomyocytes, VDAC2 promotes mitochondrial transport of calcium ions in order to power cardiac contractions. In addition, VDACs form part of the mitochondrial permeability transition pore (MPTP) and, thus, facilitate cytochrome C release, leading to apoptosis. VDACs have also been observed to interact with pro- or antiapoptotic proteins, such as Bcl-2 family proteins and kinases, and so may contribute to apoptosis independently from the MPTP. VDAC2 in particular has demonstrated a protective effect in cells undergoing mitochondrial apoptosis, and may even confer protection during aging. Furthermore, VDAcs have been linked to spermatogenesis, sperm maturation, motility, and fertilization. Though all VDAC isoforms are ubiquitously expressed, VDAC2 is majorly found in the sperm outer dense fiber (ODF), where it is hypothesized to promote proper assembly and maintenance of sperm flagella. It also localizes to the acrosomal membrane of the sperm, where it putatively mediates calcium ion transmembrane transport. # Clinical significance The VDAC2 protein belongs to a group of mitochondrial membrane channels involved in translocation of adenine nucleotides through the outer membrane. These channels may also function as a mitochondrial binding site for hexokinase and glycerol kinase. The VDAC is an important constituent in apoptotic signaling and oxidative stress, most notably as part of the mitochondrial death pathway and cardiac myocyte apoptosis signaling. Programmed cell death is a distinct genetic and biochemical pathway essential to metazoans. An intact death pathway is required for successful embryonic development and the maintenance of normal tissue homeostasis. Apoptosis has proven to be tightly interwoven with other essential cell pathways. The identification of critical control points in the cell death pathway has yielded fundamental insights for basic biology, as well as provided rational targets for new therapeutics a normal embryologic processes, or during cell injury (such as ischemia-reperfusion injury during heart attacks and strokes) or during developments and processes in cancer, an apoptotic cell undergoes structural changes including cell shrinkage, plasma membrane blebbing, nuclear condensation, and fragmentation of the DNA and nucleus. This is followed by fragmentation into apoptotic bodies that are quickly removed by phagocytes, thereby preventing an inflammatory response. It is a mode of cell death defined by characteristic morphological, biochemical and molecular changes. It was first described as a "shrinkage necrosis", and then this term was replaced by apoptosis to emphasize its role opposite mitosis in tissue kinetics. In later stages of apoptosis the entire cell becomes fragmented, forming a number of plasma membrane-bounded apoptotic bodies which contain nuclear and or cytoplasmic elements. The ultrastructural appearance of necrosis is quite different, the main features being mitochondrial swelling, plasma membrane breakdown and cellular disintegration. Apoptosis occurs in many physiological and pathological processes. It plays an important role during embryonal development as programmed cell death and accompanies a variety of normal involutional processes in which it serves as a mechanism to remove "unwanted" cells. The VDAC2 protein has been implicated in cardioprotection against ischemia-reperfusion injury, such as during ischemic preconditioning of the heart. Although a large burst of reactive oxygen species (ROS) is known to lead to cell damage, a moderate release of ROS from the mitochondria, which occurs during nonlethal short episodes of ischemia, can play a significant triggering role in the signal transduction pathways of ischemic preconditioning leading to reduction of cell damage. It has even been observed that during this release of reactive oxygen species, VDAC2 plays an important role in the mitochondrial cell death pathway transduction hereby regulating apoptotic signaling and cell death. The VDAC2 protein has been linked persistent pulmonary hypertension of the newborn (PPHN), which causes a large majority of neonatal morbidity and mortality, due to its role as a major regulator of endothelium-dependent nitric oxide synthase (eNOS) in the pulmonary endothelium. eNOS has been attributed with regulating NOS activity in response to physiological stimuli, which is vital to maintain NO production for proper blood circulation to the lungs. As a result, VDAC2 is significantly involved in pulmonary circulation and may become a therapeutic target for treating diseases such as pulmonary hypertension, VDAC2 may also serve an immune function, as it has been hypothesized to detect and induce apoptosis in cells infected by the IBD virus. IBD, the equivalent HIV in birds, can compromise their immune systems and even cause fatal injury to the lymphoid organ, Studies of this process indicate that VDAC2 interacts with the viral protein V5 to mediate cell death. # Interactions VDAC2 has been shown to interact with: - BAK - Parkin - eNOS	VDAC2 Voltage-dependent anion-selective channel protein 2 is a protein that in humans is encoded by the VDAC2 gene on chromosome 10.[1][2] This protein is a voltage-dependent anion channel and shares high structural homology with the other VDAC isoforms.[3][4][5] VDACs are generally involved in the regulation of cell metabolism, mitochondrial apoptosis, and spermatogenesis.[6][7][8][9] Additionally, VDAC2 participates in cardiac contractions and pulmonary circulation, which implicate it in cardiopulmonary diseases.[6][7] VDAC2 also mediates immune response to infectious bursal disease (IBD).[7] # Structure The three VDAC isoforms in human are highly conserved, particularly with respect to their 3D structure. VDACs form a wide β-barrel structure, inside of which the N-terminal resides to partially close the pore. The sequence of the VDAC2 isoform contains an abundance of cysteines, which allow for the formation of disulfide bridges and, ultimately, affect the flexibility of the β-barrel. VDACs also contain a mitochondrial targeting sequence for the protein's translocation to the outer mitochondrial membrane.[10] In particular, VDAC2 possesses an N-terminal longer by 11 residues compared to the other two isoforms.[5] # Function VDAC2 belongs to the mitochondrial porin family and is expected to share similar biological functions to the other VDAC isoforms. VDACs generally are involved in cellular energy metabolism by transporting ATP and other small ions and metabolites across the outer mitochondrial membrane.[6][7] In mammalian cardiomyocytes, VDAC2 promotes mitochondrial transport of calcium ions in order to power cardiac contractions.[6] In addition, VDACs form part of the mitochondrial permeability transition pore (MPTP) and, thus, facilitate cytochrome C release, leading to apoptosis.[6][11] VDACs have also been observed to interact with pro- or antiapoptotic proteins, such as Bcl-2 family proteins and kinases, and so may contribute to apoptosis independently from the MPTP.[7][9][11] VDAC2 in particular has demonstrated a protective effect in cells undergoing mitochondrial apoptosis, and may even confer protection during aging.[12][13] Furthermore, VDAcs have been linked to spermatogenesis, sperm maturation, motility, and fertilization.[9] Though all VDAC isoforms are ubiquitously expressed, VDAC2 is majorly found in the sperm outer dense fiber (ODF), where it is hypothesized to promote proper assembly and maintenance of sperm flagella.[14][15] It also localizes to the acrosomal membrane of the sperm, where it putatively mediates calcium ion transmembrane transport.[16] # Clinical significance The VDAC2 protein belongs to a group of mitochondrial membrane channels involved in translocation of adenine nucleotides through the outer membrane. These channels may also function as a mitochondrial binding site for hexokinase and glycerol kinase. The VDAC is an important constituent in apoptotic signaling and oxidative stress, most notably as part of the mitochondrial death pathway and cardiac myocyte apoptosis signaling.[17] Programmed cell death is a distinct genetic and biochemical pathway essential to metazoans. An intact death pathway is required for successful embryonic development and the maintenance of normal tissue homeostasis. Apoptosis has proven to be tightly interwoven with other essential cell pathways. The identification of critical control points in the cell death pathway has yielded fundamental insights for basic biology, as well as provided rational targets for new therapeutics a normal embryologic processes, or during cell injury (such as ischemia-reperfusion injury during heart attacks and strokes) or during developments and processes in cancer, an apoptotic cell undergoes structural changes including cell shrinkage, plasma membrane blebbing, nuclear condensation, and fragmentation of the DNA and nucleus. This is followed by fragmentation into apoptotic bodies that are quickly removed by phagocytes, thereby preventing an inflammatory response.[18] It is a mode of cell death defined by characteristic morphological, biochemical and molecular changes. It was first described as a "shrinkage necrosis", and then this term was replaced by apoptosis to emphasize its role opposite mitosis in tissue kinetics. In later stages of apoptosis the entire cell becomes fragmented, forming a number of plasma membrane-bounded apoptotic bodies which contain nuclear and or cytoplasmic elements. The ultrastructural appearance of necrosis is quite different, the main features being mitochondrial swelling, plasma membrane breakdown and cellular disintegration. Apoptosis occurs in many physiological and pathological processes. It plays an important role during embryonal development as programmed cell death and accompanies a variety of normal involutional processes in which it serves as a mechanism to remove "unwanted" cells. The VDAC2 protein has been implicated in cardioprotection against ischemia-reperfusion injury, such as during ischemic preconditioning of the heart.[19] Although a large burst of reactive oxygen species (ROS) is known to lead to cell damage, a moderate release of ROS from the mitochondria, which occurs during nonlethal short episodes of ischemia, can play a significant triggering role in the signal transduction pathways of ischemic preconditioning leading to reduction of cell damage. It has even been observed that during this release of reactive oxygen species, VDAC2 plays an important role in the mitochondrial cell death pathway transduction hereby regulating apoptotic signaling and cell death. The VDAC2 protein has been linked persistent pulmonary hypertension of the newborn (PPHN), which causes a large majority of neonatal morbidity and mortality, due to its role as a major regulator of endothelium-dependent nitric oxide synthase (eNOS) in the pulmonary endothelium. eNOS has been attributed with regulating NOS activity in response to physiological stimuli, which is vital to maintain NO production for proper blood circulation to the lungs. As a result, VDAC2 is significantly involved in pulmonary circulation and may become a therapeutic target for treating diseases such as pulmonary hypertension,[7] VDAC2 may also serve an immune function, as it has been hypothesized to detect and induce apoptosis in cells infected by the IBD virus. IBD, the equivalent HIV in birds, can compromise their immune systems and even cause fatal injury to the lymphoid organ, Studies of this process indicate that VDAC2 interacts with the viral protein V5 to mediate cell death.[9] # Interactions VDAC2 has been shown to interact with: - BAK[9][12] - Parkin[20] - eNOS[7]	https://www.wikidoc.org/index.php/VDAC2
6ad654181baf094574164df1fd820da0fd31edab	wikidoc	VDAC3	VDAC3 Voltage-dependent anion-selective channel protein 3 (VDAC3) is a protein that in humans is encoded by the VDAC3 gene on chromosome 8. The protein encoded by this gene is a voltage-dependent anion channel and shares high structural homology with the other VDAC isoforms. Nonetheless, VDAC3 demonstrates limited pore-forming ability and, instead, interacts with other proteins to perform its biological functions, including sperm flagella assembly and centriole assembly. Mutations in VDAC3 have been linked to male infertility, as well as Parkinson’s disease. # Structure The three VDAC isoforms in human are highly conserved, particularly with respect to their 3D structure. VDACs form a wide β-barrel structure, inside of which the N-terminal resides to partially close the pore. The sequence of the VDAC3 isoform contains an abundance of cysteines, which allow for the formation of disulfide bridges and, ultimately, affect the flexibility of the β-barrel. VDACs also contain a mitochondrial targeting sequence for the protein's translocation to the outer mitochondrial membrane. VDAC3 still yet possesses multiple isoforms, including a full-length form and shorter form termed VDAC3b. This shorter form is predominantly expressed over the full-length form at cell centrosomes. # Function VDAC3 belongs to the mitochondrial porin family and is expected to share similar biological functions to the other VDAC isoforms. VDACs are involved in cell metabolism by transporting ATP and other small metabolites across the outer mitochondrial membrane. In addition, VDACs form part of the mitochondrial permeability transition pore (MPTP) and, thus, facilitate cytochrome C release, leading to apoptosis. VDACs have also been observed to interact with pro- or antiapoptotic proteins, such as Bcl-2 family proteins and kinases, and so may contribute to apoptosis independently from the MPTP. Nonetheless, experiments reveal a lack of pore-forming ability in the VDAC3 isoform, suggesting that it may perform different biological functions. Notably, though all VDAC isoforms are ubiquitously expressed, VDAC3 is majorly found in the sperm outer dense fiber (ODF), where it is hypothesized to promote proper assembly and maintenance of sperm flagella. Because the ODF membranes are not likely to support pore formation, VDAC3 may interact with protein partners to carry out other functions in the ODF. For instance, within cells, VDAC3 predominantly localizes to the centrosome and recruits Mps1 to regulate centriole assembly. In the case of localization to the mitochondria, VDAC3 interaction with Mps1 instead leads to ciliary disassembly. # Clinical significance VDAC3 belongs to a group of mitochondrial membrane channels involved in translocation of adenine nucleotides through the outer membrane. These channels may also function as a mitochondrial binding site for hexokinase and glycerol kinase. The VDAC is an important constituent in apoptotic signaling and oxidative stress, most notably as part of the mitochondrial death pathway and cardiac myocyte apoptosis signaling. Programmed cell death is a distinct genetic and biochemical pathway essential to metazoans. An intact death pathway is required for successful embryonic development and the maintenance of normal tissue homeostasis. Apoptosis has proven to be tightly interwoven with other essential cell pathways. The identification of critical control points in the cell death pathway has yielded fundamental insights for basic biology, as well as provided rational targets for new therapeutics a normal embryologic processes, or during cell injury (such as ischemia-reperfusion injury during heart attacks and strokes) or during developments and processes in cancer, an apoptotic cell undergoes structural changes including cell shrinkage, plasma membrane blebbing, nuclear condensation, and fragmentation of the DNA and nucleus. This is followed by fragmentation into apoptotic bodies that are quickly removed by phagocytes, thereby preventing an inflammatory response. It is a mode of cell death defined by characteristic morphological, biochemical and molecular changes. It was first described as a "shrinkage necrosis", and then this term was replaced by apoptosis to emphasize its role opposite mitosis in tissue kinetics. In later stages of apoptosis the entire cell becomes fragmented, forming a number of plasma membrane-bounded apoptotic bodies which contain nuclear and or cytoplasmic elements. The ultrastructural appearance of necrosis is quite different, the main features being mitochondrial swelling, plasma membrane breakdown and cellular disintegration. Apoptosis occurs in many physiological and pathological processes. It plays an important role during embryonal development as programmed cell death and accompanies a variety of normal involutional processes in which it serves as a mechanism to remove "unwanted" cells. In addition, VDAC3 has been implicated in cardioprotection against ischemia-reperfusion injury, such as during ischemic preconditioning of the heart. Although a large burst of reactive oxygen species is known to lead to cell damage, a moderate release of ROS from the mitochondria, which occurs during nonlethal short episodes of ischemia, can play a significant triggering role in the signal transduction pathways of ischemic preconditioning leading to reduction of cell damage. It has even been observed that during this release of reactive oxygen species, VDAC3 plays an important role in the mitochondrial cell death pathway transduction hereby regulating apoptotic signaling and cell death. As VDAC3 is a regulator of sperm motility, male mice missing VDAC3 result in infertility. Mutations in VDAC3 are also associated with Parkinson’s disease, as VDAC3 has been observed to target Parkin to defective mitochondria to eliminate them by mitophagy. Failure to eliminate these mitochondria result in the accumulation of reactive oxygen species, the commonly attributed cause of Parkinson’s disease. In addition, it has been found that VDAC3-null mice were born at the expected mendelian ratio. Mutant females were fertile, but males were not due to markedly reduced sperm motility. The majority of epididymal axonemes showed structural defects, most commonly loss of a single microtubule doublet at a conserved position within the axoneme. In testicular sperm, the defect was only rarely observed, suggesting that instability of a normally formed axoneme occurred during sperm maturation. In contrast, tracheal epithelial cilia showed no structural abnormalities, but there was a reduced number of ciliated cells. In skeletal muscle, mitochondria were abnormally shaped, and the activities of respiratory chain complex enzymes were reduced. Citrate synthase activity was unchanged, suggesting an absence of mitochondrial proliferation that commonly occurs in response to respiratory chain defects. # Interactions VDAC3 has been shown to interact with: - Mps1 - Parkin	VDAC3 Voltage-dependent anion-selective channel protein 3 (VDAC3) is a protein that in humans is encoded by the VDAC3 gene on chromosome 8. [1][2] The protein encoded by this gene is a voltage-dependent anion channel and shares high structural homology with the other VDAC isoforms.[1][2][3] Nonetheless, VDAC3 demonstrates limited pore-forming ability and, instead, interacts with other proteins to perform its biological functions, including sperm flagella assembly and centriole assembly.[4][5] Mutations in VDAC3 have been linked to male infertility, as well as Parkinson’s disease.[6][7] # Structure The three VDAC isoforms in human are highly conserved, particularly with respect to their 3D structure. VDACs form a wide β-barrel structure, inside of which the N-terminal resides to partially close the pore. The sequence of the VDAC3 isoform contains an abundance of cysteines, which allow for the formation of disulfide bridges and, ultimately, affect the flexibility of the β-barrel.[3] VDACs also contain a mitochondrial targeting sequence for the protein's translocation to the outer mitochondrial membrane.[8] VDAC3 still yet possesses multiple isoforms, including a full-length form and shorter form termed VDAC3b. This shorter form is predominantly expressed over the full-length form at cell centrosomes.[4] # Function VDAC3 belongs to the mitochondrial porin family and is expected to share similar biological functions to the other VDAC isoforms. VDACs are involved in cell metabolism by transporting ATP and other small metabolites across the outer mitochondrial membrane. In addition, VDACs form part of the mitochondrial permeability transition pore (MPTP) and, thus, facilitate cytochrome C release, leading to apoptosis.[9] VDACs have also been observed to interact with pro- or antiapoptotic proteins, such as Bcl-2 family proteins and kinases, and so may contribute to apoptosis independently from the MPTP.[10] Nonetheless, experiments reveal a lack of pore-forming ability in the VDAC3 isoform, suggesting that it may perform different biological functions.[6][11] Notably, though all VDAC isoforms are ubiquitously expressed, VDAC3 is majorly found in the sperm outer dense fiber (ODF), where it is hypothesized to promote proper assembly and maintenance of sperm flagella.[4][5] Because the ODF membranes are not likely to support pore formation, VDAC3 may interact with protein partners to carry out other functions in the ODF.[12] For instance, within cells, VDAC3 predominantly localizes to the centrosome and recruits Mps1 to regulate centriole assembly.[4][5] In the case of localization to the mitochondria, VDAC3 interaction with Mps1 instead leads to ciliary disassembly.[5] # Clinical significance VDAC3 belongs to a group of mitochondrial membrane channels involved in translocation of adenine nucleotides through the outer membrane. These channels may also function as a mitochondrial binding site for hexokinase and glycerol kinase. The VDAC is an important constituent in apoptotic signaling and oxidative stress, most notably as part of the mitochondrial death pathway and cardiac myocyte apoptosis signaling.[13] Programmed cell death is a distinct genetic and biochemical pathway essential to metazoans. An intact death pathway is required for successful embryonic development and the maintenance of normal tissue homeostasis. Apoptosis has proven to be tightly interwoven with other essential cell pathways. The identification of critical control points in the cell death pathway has yielded fundamental insights for basic biology, as well as provided rational targets for new therapeutics a normal embryologic processes, or during cell injury (such as ischemia-reperfusion injury during heart attacks and strokes) or during developments and processes in cancer, an apoptotic cell undergoes structural changes including cell shrinkage, plasma membrane blebbing, nuclear condensation, and fragmentation of the DNA and nucleus. This is followed by fragmentation into apoptotic bodies that are quickly removed by phagocytes, thereby preventing an inflammatory response.[14] It is a mode of cell death defined by characteristic morphological, biochemical and molecular changes. It was first described as a "shrinkage necrosis", and then this term was replaced by apoptosis to emphasize its role opposite mitosis in tissue kinetics. In later stages of apoptosis the entire cell becomes fragmented, forming a number of plasma membrane-bounded apoptotic bodies which contain nuclear and or cytoplasmic elements. The ultrastructural appearance of necrosis is quite different, the main features being mitochondrial swelling, plasma membrane breakdown and cellular disintegration. Apoptosis occurs in many physiological and pathological processes. It plays an important role during embryonal development as programmed cell death and accompanies a variety of normal involutional processes in which it serves as a mechanism to remove "unwanted" cells. In addition, VDAC3 has been implicated in cardioprotection against ischemia-reperfusion injury, such as during ischemic preconditioning of the heart.[15] Although a large burst of reactive oxygen species is known to lead to cell damage, a moderate release of ROS from the mitochondria, which occurs during nonlethal short episodes of ischemia, can play a significant triggering role in the signal transduction pathways of ischemic preconditioning leading to reduction of cell damage. It has even been observed that during this release of reactive oxygen species, VDAC3 plays an important role in the mitochondrial cell death pathway transduction hereby regulating apoptotic signaling and cell death. As VDAC3 is a regulator of sperm motility, male mice missing VDAC3 result in infertility.[6] Mutations in VDAC3 are also associated with Parkinson’s disease, as VDAC3 has been observed to target Parkin to defective mitochondria to eliminate them by mitophagy. Failure to eliminate these mitochondria result in the accumulation of reactive oxygen species, the commonly attributed cause of Parkinson’s disease.[7] In addition, it has been found that VDAC3-null mice were born at the expected mendelian ratio. Mutant females were fertile, but males were not due to markedly reduced sperm motility.[16] The majority of epididymal axonemes showed structural defects, most commonly loss of a single microtubule doublet at a conserved position within the axoneme. In testicular sperm, the defect was only rarely observed, suggesting that instability of a normally formed axoneme occurred during sperm maturation. In contrast, tracheal epithelial cilia showed no structural abnormalities, but there was a reduced number of ciliated cells. In skeletal muscle, mitochondria were abnormally shaped, and the activities of respiratory chain complex enzymes were reduced. Citrate synthase activity was unchanged, suggesting an absence of mitochondrial proliferation that commonly occurs in response to respiratory chain defects. # Interactions VDAC3 has been shown to interact with: - Mps1[4] - Parkin[7]	https://www.wikidoc.org/index.php/VDAC3
3c4c1e7e73d889b5d64b4fa9204111c52db00584	wikidoc	VIPR1	VIPR1 Vasoactive intestinal polypeptide receptor 1 also known as VPAC1, is a protein, that in humans is encoded by the VIPR1 gene. VPAC1 is expressed in the brain (cerebral cortex, hippocampus, amygdala), lung, prostate, peripheral blood leukocytes, liver, small intestine, heart, spleen, placenta, kidney, thymus and testis. # Function VPAC1 is a receptor for vasoactive intestinal peptide (VIP), a small neuropeptide. Vasoactive intestinal peptide is involved in smooth muscle relaxation, exocrine and endocrine secretion, and water and ion flux in lung and intestinal epithelia. Its actions are effected through integral membrane receptors associated with a guanine nucleotide binding protein which activates adenylate cyclase. VIP acts in an autocrine fashion via VPAC11 to inhibit megakaryocyte proliferation and induce proplatelet formation. # Clinical significance Patients with idiopathic achalasia show a significant difference in the distribution of SNPs affecting VIPR1. VIP and PACAP levels were decreased in anterior vaginal wall of stress urinary incontinence and pelvic organ prolapse patients, they may participate in the pathophysiology of these diseases.	VIPR1 Vasoactive intestinal polypeptide receptor 1 also known as VPAC1, is a protein, that in humans is encoded by the VIPR1 gene.[1] VPAC1 is expressed in the brain (cerebral cortex, hippocampus, amygdala), lung, prostate, peripheral blood leukocytes, liver, small intestine, heart, spleen, placenta, kidney, thymus and testis.[2][3][4] # Function VPAC1 is a receptor for vasoactive intestinal peptide (VIP), a small neuropeptide. Vasoactive intestinal peptide is involved in smooth muscle relaxation, exocrine and endocrine secretion, and water and ion flux in lung and intestinal epithelia. Its actions are effected through integral membrane receptors associated with a guanine nucleotide binding protein which activates adenylate cyclase.[1] VIP acts in an autocrine fashion via VPAC11 to inhibit megakaryocyte proliferation and induce proplatelet formation.[5][6] # Clinical significance Patients with idiopathic achalasia show a significant difference in the distribution of SNPs affecting VIPR1.[7] VIP and PACAP levels were decreased in anterior vaginal wall of stress urinary incontinence and pelvic organ prolapse patients, they may participate in the pathophysiology of these diseases.[8]	https://www.wikidoc.org/index.php/VIPR1
1d4c68261e76ffa5c4cd01ae8c6a58067773cfd4	wikidoc	VIPR2	VIPR2 Vasoactive intestinal peptide receptor 2 also known as VPAC2, is a G-protein coupled receptor that in humans is encoded by the VIPR2 gene. # Tissue distribution VIPR2 is expressed in the uterus, prostate, smooth muscle of the gastrointestinal tract, seminal vesicles and skin, blood vessels and thymus. VIPR2 is also expressed in the cerebellum. # Function Vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase activating polypeptide (PACAP) are homologous peptides that function as neurotransmitters and neuroendocrine hormones. While the receptors for VIP (VIRP 1 and 2) and PACAP (ADCYAP1R1) share homology, they differ in their substrate specificities and expression patterns. VIPR2 transduction results in upregulation of adenylate cyclase activity. Furthermore, VIPR2 mediates the anti-inflammatory effects of VIP. Research using VPAC2 knockout mice implicate it in the function of the circadian clock, growth, basal energy expenditure and male reproduction. VIPR2 and/or PAC1 receptor activation is involved in cutaneous active vasodilation in humans. Splice variants may modify the immunoregulatory contributions of the VIP-VIPR2 axis. VIPR2 may contribute to autoregulation and/or coupling within the suprachiasmatic nucleus (SCN) core and to control of the SCN shell. # Clinical significance VIPR2 may play a role in schizophrenia. The abnormal expression of VIPR2 messenger RNA in gallbladder tissue may play a role in the formation of gall stones and polyps.	VIPR2 Vasoactive intestinal peptide receptor 2 also known as VPAC2, is a G-protein coupled receptor that in humans is encoded by the VIPR2 gene.[1] # Tissue distribution VIPR2 is expressed in the uterus, prostate, smooth muscle of the gastrointestinal tract, seminal vesicles and skin, blood vessels and thymus.[2][3] VIPR2 is also expressed in the cerebellum.[4] # Function Vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase activating polypeptide (PACAP) are homologous peptides that function as neurotransmitters and neuroendocrine hormones. While the receptors for VIP (VIRP 1 and 2) and PACAP (ADCYAP1R1) share homology, they differ in their substrate specificities and expression patterns.[1] VIPR2 transduction results in upregulation of adenylate cyclase activity.[5] Furthermore, VIPR2 mediates the anti-inflammatory effects of VIP.[6] Research using VPAC2 knockout mice implicate it in the function of the circadian clock, growth, basal energy expenditure and male reproduction.[7][8][9][10] VIPR2 and/or PAC1 receptor activation is involved in cutaneous active vasodilation in humans.[11] Splice variants may modify the immunoregulatory contributions of the VIP-VIPR2 axis.[12] VIPR2 may contribute to autoregulation and/or coupling within the suprachiasmatic nucleus (SCN) core and to control of the SCN shell.[13] # Clinical significance VIPR2 may play a role in schizophrenia.[14] The abnormal expression of VIPR2 messenger RNA in gallbladder tissue may play a role in the formation of gall stones and polyps.[15]	https://www.wikidoc.org/index.php/VIPR2
22f5d9c5333e4746054917e926c9b3b53558d68a	wikidoc	VLA-4	VLA-4 Integrin α4β1 (Very Late Antigen-4) is an integrin dimer. It is composed of CD49d (alpha 4) and CD29 (beta 1). The alpha 4 subunit is 155 kDa, and the beta 1 subunit is 150 kDa. # Function The integrin VLA-4 is expressed on the cell surfaces of stem cells, progenitor cells, T and B cells, monocytes, natural killer cells, eosinophils, and neutrophils. It functions to promote an inflammatory response by the immune system by assisting in the movement of leukocytes to tissue that requires inflammation. It is a key player in cell adhesion. However, VLA-4 does not adhere to its appropriate ligands until the leukocytes are activated by chemotactic agents or other stimuli (often produced by the endothelium or other cells at the site of injury). VLA-4's primary ligands include VCAM-1 and fibronectin. One activating chemokine is SDF-1. Following SDF-1 binding, the integrin undergoes a conformational change of the alpha and beta domains that is necessary to confer high binding affinity for the endothelial adhesion molecules. This change is achieved by talin or kindlin interacting with the parts of VLA-4 on the inside of the cell's surface. The expression of VLA-4 in the plasma membrane is regulated by different growth factors or chemokines depending on the cell type. In T cells, IL-4 down-regulates the expression of VLA-4. In CD34 positive cells, IL-3 and SCF cause up-regulation, and G-CSF causes down-regulation (stem cells are CD34 positive cells). # Role in hematopoiesis VLA-4 can be found on hematopoietic stem and progenitor cells. These cells are found in the bone marrow, as that is where they are produced, and throughout the rest of the body. VLA-4, specifically the alpha subunit, is crucial for the localization and circulation of progenitor cells. In mice, it has been shown that injected anti-alpha antibodies result in an increase in progenitor cell circulation and duration. In order for stem cells to move into the peripheral blood stream, VLA-4 must be down-regulated on the cell surface of PBSCs. # Clinical significance ## Stem and Progenitor cells There is possibility for stem cell therapy through stimulation the conformational change. This is currently being studied in the field. When the alpha unit was knocked out in mice, it resulted in an embryonic lethal mutation. ## Multiple sclerosis In multiple sclerosis, the VLA-4 integrin is essential in the processes by which T-cells gain access to the brain. It allows the cells to penetrate the blood brain barrier that normally restricts immune cell access. It has been found that the severity of MS is positively correlated with the expression of alpha 4. One approach to prevent an autoimmune reaction has been to block the action of VLA-4 so that self-reactive T-cells are unable to enter the brain and thus unable to attack myelin protein. It has been found that in mice, anti-alpha 4 integrin antibodies resulted in an increase of circulating stem cell and progenitor cells. Though this failed in initial multiple sclerosis research, it is still being investigated. ## Treating other inflammatory issues VLA-4 antagonists have also shown potential for the treatment of several inflammatory disorders. In addition to MS, a humanized antibody, Antegren®, has been considered for treating asthma. There was some success in the initial human trials in treating Crohn's disease-- over 40% remission was witnessed. However, the usage of Natalizumab, an antagonist of VLA-4 integrin, remains controversial due to several side effects including Progressive multifocal leukoencephalopathy. Other allosteric antagonists have been identified that decrease VLA-4 ligand binding affinity. ## Chemotherapy Sensitivity Additionally, it has been shown that VLA-4-ligand interactions can affect the sensitivity to chemotherapy in patients with malignancies in blood-forming tissue.	VLA-4 Integrin α4β1 (Very Late Antigen-4) is an integrin dimer. It is composed of CD49d (alpha 4) and CD29 (beta 1). The alpha 4 subunit is 155 kDa, and the beta 1 subunit is 150 kDa.[1] # Function The integrin VLA-4 is expressed on the cell surfaces of stem cells, progenitor cells, T and B cells, monocytes, natural killer cells, eosinophils, and neutrophils. It functions to promote an inflammatory response by the immune system by assisting in the movement of leukocytes to tissue that requires inflammation.[2] It is a key player in cell adhesion.[3] However, VLA-4 does not adhere to its appropriate ligands until the leukocytes are activated by chemotactic agents or other stimuli (often produced by the endothelium or other cells at the site of injury). VLA-4's primary ligands include VCAM-1 and fibronectin.[4] One activating chemokine is SDF-1. Following SDF-1 binding, the integrin undergoes a conformational change of the alpha and beta domains that is necessary to confer high binding affinity for the endothelial adhesion molecules. This change is achieved by talin or kindlin interacting with the parts of VLA-4 on the inside of the cell's surface.[4] The expression of VLA-4 in the plasma membrane is regulated by different growth factors or chemokines depending on the cell type. In T cells, IL-4 down-regulates the expression of VLA-4. In CD34 positive cells, IL-3 and SCF cause up-regulation, and G-CSF causes down-regulation (stem cells are CD34 positive cells).[4] # Role in hematopoiesis VLA-4 can be found on hematopoietic stem and progenitor cells. These cells are found in the bone marrow, as that is where they are produced, and throughout the rest of the body. VLA-4, specifically the alpha subunit, is crucial for the localization and circulation of progenitor cells. In mice, it has been shown that injected anti-alpha antibodies result in an increase in progenitor cell circulation and duration.[1] In order for stem cells to move into the peripheral blood stream, VLA-4 must be down-regulated on the cell surface of PBSCs.[5] # Clinical significance ## Stem and Progenitor cells There is possibility for stem cell therapy through stimulation the conformational change. This is currently being studied in the field. When the alpha unit was knocked out in mice, it resulted in an embryonic lethal mutation.[4] ## Multiple sclerosis In multiple sclerosis, the VLA-4 integrin is essential in the processes by which T-cells gain access to the brain. It allows the cells to penetrate the blood brain barrier that normally restricts immune cell access. It has been found that the severity of MS is positively correlated with the expression of alpha 4.[6] One approach to prevent an autoimmune reaction has been to block the action of VLA-4 so that self-reactive T-cells are unable to enter the brain and thus unable to attack myelin protein.[7] It has been found that in mice, anti-alpha 4 integrin antibodies resulted in an increase of circulating stem cell and progenitor cells. Though this failed in initial multiple sclerosis research, it is still being investigated.[4] ## Treating other inflammatory issues VLA-4 antagonists have also shown potential for the treatment of several inflammatory disorders. In addition to MS, a humanized antibody, Antegren®, has been considered for treating asthma.[2] There was some success in the initial human trials in treating Crohn's disease-- over 40% remission was witnessed.[8] However, the usage of Natalizumab, an antagonist of VLA-4 integrin, remains controversial due to several side effects including Progressive multifocal leukoencephalopathy. Other allosteric antagonists have been identified that decrease VLA-4 ligand binding affinity.[9] ## Chemotherapy Sensitivity Additionally, it has been shown that VLA-4-ligand interactions can affect the sensitivity to chemotherapy in patients with malignancies in blood-forming tissue.[4]	https://www.wikidoc.org/index.php/VLA-4
a87d1a5e8796bfd21a7bbe99cb4722a156d817e1	wikidoc	VPS11	VPS11 Vacuolar protein sorting-associated protein 11 homolog is a protein that in humans is encoded by the VPS11 gene. # Function Vesicle mediated protein sorting plays an important role in segregation of intracellular molecules into distinct organelles. Genetic studies in yeast have identified more than 40 vacuolar protein sorting (VPS) genes involved in vesicle transport to vacuoles. This gene encodes the human homolog of yeast class C Vps11 protein. The mammalian class C Vps proteins are predominantly associated with late endosomes/lysosomes, and like their yeast counterparts, may mediate vesicle trafficking steps in the endosome/lysosome pathway. # Interactions VPS11 has been shown to interact with VPS18, VPS33A and STX7.	VPS11 Vacuolar protein sorting-associated protein 11 homolog is a protein that in humans is encoded by the VPS11 gene.[1] # Function Vesicle mediated protein sorting plays an important role in segregation of intracellular molecules into distinct organelles. Genetic studies in yeast have identified more than 40 vacuolar protein sorting (VPS) genes involved in vesicle transport to vacuoles. This gene encodes the human homolog of yeast class C Vps11 protein. The mammalian class C Vps proteins are predominantly associated with late endosomes/lysosomes, and like their yeast counterparts, may mediate vesicle trafficking steps in the endosome/lysosome pathway.[1] # Interactions VPS11 has been shown to interact with VPS18,[2] VPS33A[2] and STX7.[2]	https://www.wikidoc.org/index.php/VPS11
f60410908c336a734735840612eb660f091da200	wikidoc	VPS25	VPS25 Vacuolar protein-sorting-associated protein 25 is a protein that in humans is encoded by the VPS25 gene. It is a component of the endosome-associated complex ESCRT-II (Endosomal Sorting Complexes Required for Transport protein II). ESCRT (ESCRT-I, -II, -III) complexes orchestrate efficient sorting of ubiquitinated transmembrane receptors to lysosomes via multivesicular bodies (MVBs). ESCRT-II recruits the transport machinery for protein sorting at MVB. In addition, the human ESCRT-II has been shown to form a complex with RNA polymerase II elongation factor ELL in order to exert transcriptional control activity. ESCRT-II transiently associates with the endosomal membrane and thereby initiates the formation of ESCRT-III, a membrane-associated protein complex that functions immediately downstream of ESCRT-II during sorting of MVB cargo. ESCRT-II in turn functions downstream of ESCRT-I, a protein complex that binds to ubiquitinated endosomal cargo. ESCRT-II is a trilobal complex composed of two copies of vps25, one copy of vps22 and the C-terminal region of vps36. The crystal structure of vps25 revealed two winged-helix domains, the N-terminal domain of vps25 interacting with vps22 and vps36.	VPS25 Vacuolar protein-sorting-associated protein 25 is a protein that in humans is encoded by the VPS25 gene.[1][2] It is a component of the endosome-associated complex ESCRT-II (Endosomal Sorting Complexes Required for Transport protein II). ESCRT (ESCRT-I, -II, -III) complexes orchestrate efficient sorting of ubiquitinated transmembrane receptors to lysosomes via multivesicular bodies (MVBs).[3] ESCRT-II recruits the transport machinery for protein sorting at MVB.[4] In addition, the human ESCRT-II has been shown to form a complex with RNA polymerase II elongation factor ELL in order to exert transcriptional control activity. ESCRT-II transiently associates with the endosomal membrane and thereby initiates the formation of ESCRT-III, a membrane-associated protein complex that functions immediately downstream of ESCRT-II during sorting of MVB cargo. ESCRT-II in turn functions downstream of ESCRT-I, a protein complex that binds to ubiquitinated endosomal cargo.[5] ESCRT-II is a trilobal complex composed of two copies of vps25, one copy of vps22 and the C-terminal region of vps36. The crystal structure of vps25 revealed two winged-helix domains, the N-terminal domain of vps25 interacting with vps22 and vps36.[6]	https://www.wikidoc.org/index.php/VPS25
1cbe3e30725af22ddd9c89c9a110801f2c82bae1	wikidoc	VPS29	VPS29 VPS29 is a human gene coding for the vacuolar protein sorting protein Vps29, a component of the retromer complex. # Yeast homolog The homologous protein (one that performs the same function) in yeast is Vacuolar protein sorting 29 homolog (S. cerevisiae). # Function VPS29 belongs to a group of genes coding for vacuolar protein sorting (VPS) proteins that, when functionally impaired, disrupt the efficient delivery of vacuolar hydrolases. The protein encoded by this gene, Vps29, is a component of a large multimeric complex, termed the retromer complex, which is involved in retrograde transport of proteins from endosomes to the trans-Golgi network. Vps29 may be involved in the formation of the inner shell of the retromer coat for retrograde vesicles leaving the prevacuolar compartment. Alternative splice variants encoding different isoforms, and usage of multiple polyadenylation sites have been found for this gene.	VPS29 VPS29 is a human gene coding for the vacuolar protein sorting protein Vps29, a component of the retromer complex.[1] # Yeast homolog The homologous protein (one that performs the same function) in yeast is Vacuolar protein sorting 29 homolog (S. cerevisiae).[2] # Function VPS29 belongs to a group of genes coding for vacuolar protein sorting (VPS) proteins that, when functionally impaired, disrupt the efficient delivery of vacuolar hydrolases.[3] The protein encoded by this gene, Vps29, is a component of a large multimeric complex, termed the retromer complex, which is involved in retrograde transport of proteins from endosomes to the trans-Golgi network. Vps29 may be involved in the formation of the inner shell of the retromer coat for retrograde vesicles leaving the prevacuolar compartment.[4] Alternative splice variants encoding different isoforms, and usage of multiple polyadenylation sites have been found for this gene.[2]	https://www.wikidoc.org/index.php/VPS29
567e4263615c73b80d7fb444b08ed17437993e44	wikidoc	VPS35	VPS35 Vacuolar protein sorting-associated protein 35 is a protein that in humans is encoded by the VPS35 gene. This gene belongs to a group of vacuolar protein sorting (VPS) genes. The encoded protein is a component of a large multimeric complex, termed the retromer complex, involved in retrograde transport of proteins from endosomes to the trans-Golgi network. The close structural similarity between the yeast and human proteins that make up this complex suggests a similarity in function. Expression studies in yeast and mammalian cells indicate that this protein interacts directly with VPS35, which serves as the core of the retromer complex. # Structure Vps35 is the largest subunit of retromer with the molecular weight of 92-kDa and functions as the central platform for the assembly of Vps26 and Vps29. Vps35 resembles many other helical solenoid proteins including AP adaptor protein complexes that are characterized with repeated structural units in a continuous superhelix arrangement involved in coated vesicle trafficking. The curved surface of the 6 even-numbered helices within solenoid structure with series of ridges separating hydrophobic grooves function as potential cargo binding sites. The C-terminal of Vps35 contains an α-solenoid fold that fits into the metal binding pocket of Vps29. A conserved PRLYL motif at the N-terminus of Vps35 is involved in the binding of Vps26. The structural binding motifs enable this subunit to act as a linker between the SNX dimers and Vps trimer complex, and the binding sites targeting to the N-terminal region of SNX subunits are located at the both ends of the trimer. A study has shown that the knockdown of Vps35 in human HEp-2 epithelial cells had defect on the endosomal recycling of transferrin by DMT1 due to the mis-sorting of DMT1-II to the lysosomal membrane associated protein (LAMP2) structures.	VPS35 Vacuolar protein sorting-associated protein 35 is a protein that in humans is encoded by the VPS35 gene.[1][2] This gene belongs to a group of vacuolar protein sorting (VPS) genes. The encoded protein is a component of a large multimeric complex, termed the retromer complex, involved in retrograde transport of proteins from endosomes to the trans-Golgi network. The close structural similarity between the yeast and human proteins that make up this complex suggests a similarity in function. Expression studies in yeast and mammalian cells indicate that this protein interacts directly with VPS35, which serves as the core of the retromer complex.[2] # Structure Vps35 is the largest subunit of retromer with the molecular weight of 92-kDa and functions as the central platform for the assembly of Vps26 and Vps29.[3] Vps35 resembles many other helical solenoid proteins including AP adaptor protein complexes that are characterized with repeated structural units in a continuous superhelix arrangement involved in coated vesicle trafficking. The curved surface of the 6 even-numbered helices within solenoid structure with series of ridges separating hydrophobic grooves function as potential cargo binding sites.[4] The C-terminal of Vps35 contains an α-solenoid fold that fits into the metal binding pocket of Vps29.[5] A conserved PRLYL motif at the N-terminus of Vps35 is involved in the binding of Vps26.[6][7] The structural binding motifs enable this subunit to act as a linker between the SNX dimers and Vps trimer complex, and the binding sites targeting to the N-terminal region of SNX subunits are located at the both ends of the trimer. A study has shown that the knockdown of Vps35 in human HEp-2 epithelial cells had defect on the endosomal recycling of transferrin by DMT1 due to the mis-sorting of DMT1-II to the lysosomal membrane associated protein (LAMP2) structures.[8]	https://www.wikidoc.org/index.php/VPS35
34acfed0e7fb38d80f7536029af19a1ab30a1c10	wikidoc	VPS53	VPS53 Vacuolar protein sorting 53 homolog (S. cerevisiae) is a protein that in humans is encoded by the VPS53 gene. # Function This gene encodes a protein with sequence similarity to the yeast Vps53p protein. Vps53p is involved in retrograde vesicle trafficking in late Golgi. . Mutations in VPS53 cause cerebello-cerebral atrophy type 2 .	VPS53 Vacuolar protein sorting 53 homolog (S. cerevisiae) is a protein that in humans is encoded by the VPS53 gene.[1] # Function This gene encodes a protein with sequence similarity to the yeast Vps53p protein. Vps53p is involved in retrograde vesicle trafficking in late Golgi. [provided by RefSeq, Jul 2008]. Mutations in VPS53 cause cerebello-cerebral atrophy type 2 .[2]	https://www.wikidoc.org/index.php/VPS53
89649e39397d676bcd1be6c997392f15f7079274	wikidoc	Vinca	Vinca Vinca (from Latin vincire "to bind, fetter") is a genus of five species in the family Apocynaceae, native to Europe, northwest Africa and southwest Asia. The common name, shared with the related genus Catharanthus, is Periwinkle. They are subshrubs or herbaceous, and have slender trailing stems 1-2 m (3-6 feet) long but not growing more than 20-70 cm (8-30 inches) above ground; the stems frequently take root where they touch the ground, enabling the plant to spread widely. The leaves are opposite, simple broad lanceolate to ovate, 1-9 cm (0.25-3.5 inches) long and 0.5-6 cm (0.25-2.25 inches) broad; they are evergreen in four species, but deciduous in the herbaceous V. herbacea, which dies back to the root system in winter. The flowers, produced through most of the year, are salverform (like those of Phlox), simple, 2.5-7 cm (1-3 inches) broad, with five usually violet (occasionally white) petals joined together at the base to form a tube. The fruit consists of a group of divergent follicles; a dry fruit which is dehiscent along one rupture site in order to release seeds. # Cultivation and uses Two species, the Small Periwinkle V. minor and the Large Periwinkle V. major, are very popular ornamental plants in gardens, grown for dense evergreen ground cover and their delicate violet flowers. V. major has broader leaves with a hairy margin and larger flowers, is less cold hardy, and has twice as many chromosomes as V. minor. A variegated selection of V. major is commonly cultivated. Both species are considered invasive weeds in parts of the United States and Australia. They do not respond to common herbicides and require hormone based sprays to control. ## Medical uses This plant was formerly used in homeopathy for catarrh, dyspepsia but due to the nature and effects of the alkaloids vincamine, isovincamine and vincamidine, it is rarely used. This plant also contains tannin. All parts of the periwinkles may cause stomach distress if ingested. The chemotherapy drugs vincristine and vinblastine are derived from this plant.	Vinca Vinca (from Latin vincire "to bind, fetter") is a genus of five species in the family Apocynaceae, native to Europe, northwest Africa and southwest Asia. The common name, shared with the related genus Catharanthus, is Periwinkle. They are subshrubs or herbaceous, and have slender trailing stems 1-2 m (3-6 feet) long but not growing more than 20-70 cm (8-30 inches) above ground; the stems frequently take root where they touch the ground, enabling the plant to spread widely. The leaves are opposite, simple broad lanceolate to ovate, 1-9 cm (0.25-3.5 inches) long and 0.5-6 cm (0.25-2.25 inches) broad; they are evergreen in four species, but deciduous in the herbaceous V. herbacea, which dies back to the root system in winter. The flowers, produced through most of the year, are salverform (like those of Phlox), simple, 2.5-7 cm (1-3 inches) broad, with five usually violet (occasionally white) petals joined together at the base to form a tube. The fruit consists of a group of divergent follicles; a dry fruit which is dehiscent along one rupture site in order to release seeds. # Cultivation and uses Two species, the Small Periwinkle V. minor and the Large Periwinkle V. major, are very popular ornamental plants in gardens, grown for dense evergreen ground cover and their delicate violet flowers. V. major has broader leaves with a hairy margin and larger flowers, is less cold hardy, and has twice as many chromosomes as V. minor. A variegated selection of V. major is commonly cultivated. Both species are considered invasive weeds in parts of the United States and Australia. They do not respond to common herbicides and require hormone based sprays to control. ## Medical uses This plant was formerly used in homeopathy for catarrh, dyspepsia but due to the nature and effects of the alkaloids vincamine, isovincamine and vincamidine, it is rarely used. This plant also contains tannin. All parts of the periwinkles may cause stomach distress if ingested.[1] The chemotherapy drugs vincristine and vinblastine are derived from this plant.	https://www.wikidoc.org/index.php/Vinca
a892545ad5e44588b20cb5e3d5aa1f198ce891fe	wikidoc	Vomer	Vomer The vomer (from Latin vomer, -ĕris, "ploughshare") is one of the unpaired facial bones of the skull. It is located in the midsagittal line, and touches the sphenoid, the ethmoid, the left and right palatine bones, and the left and right maxillary bones. # Vomeronasal organ The vomeronasal organ, also called Jacobson's organ, is a chemoreceptor organ named for its closeness to the vomer and nasal bones, and is particularly developed in animals such as cats (who adopt a characteristic pose called the Flehmen reaction or flehming when making use of it), and is thought to have to do with the perception of certain pheromones. # Anatomical details The vomer is situated in the median plane, but its anterior portion is frequently bent to one or other side. It is thin, somewhat quadrilateral in shape, and forms the hinder and lower part of the nasal septum; it has two surfaces and four borders. The surfaces are marked by small furrows for blood vessels, and on each is the nasopalatine groove, which runs obliquely downward and forward, and lodges the nasopalatine nerve and vessels. The superior border, the thickest, presents a deep furrow, bounded on either side by a horizontal projecting ala of bone; the furrow receives the rostrum of the sphenoid, while the margins of the alæ articulate with the vaginal processes of the medial pterygoid plates of the sphenoid behind, and with the sphenoidal processes of the palatine bones in front. The inferior border articulates with the crest formed by the maxillæ and palatine bones. The anterior border is the longest and slopes downward and forward. Its upper half is fused with the perpendicular plate of the ethmoid; its lower half is grooved for the inferior margin of the septal cartilage of the nose. The posterior border is free, concave, and separates the choanae. It is thick and bifid above, thin below. # Articulations The vomer articulates with six bones: - two of the cranium, the sphenoid and ethmoid. - four of the face, the two maxillae; and the two palatine bones. It also articulates with the septal cartilage of the nose. # Trivia By alternately thrusting with the tongue against the roof of the mouth and pressing with one of the fingers between the two eyebrows, one can articulate the vomer bone. This process, repeated for about 20 seconds, will cause the sinuses to discharge, thus rapidly clearing a stuffy head without the use of drugs. # Additional images - Median wall of left nasal cavity showing vomer in situ. - The vomer. - Base of skull. Inferior surface. - The skull from the front. - Sagittal section of skull.	Vomer Template:Infobox Anatomy The vomer (from Latin vomer, -ĕris, "ploughshare") is one of the unpaired facial bones of the skull. It is located in the midsagittal line, and touches the sphenoid, the ethmoid, the left and right palatine bones, and the left and right maxillary bones. # Vomeronasal organ The vomeronasal organ, also called Jacobson's organ, is a chemoreceptor organ named for its closeness to the vomer and nasal bones, and is particularly developed in animals such as cats (who adopt a characteristic pose called the Flehmen reaction or flehming when making use of it), and is thought to have to do with the perception of certain pheromones. # Anatomical details The vomer is situated in the median plane, but its anterior portion is frequently bent to one or other side. It is thin, somewhat quadrilateral in shape, and forms the hinder and lower part of the nasal septum; it has two surfaces and four borders. The surfaces are marked by small furrows for blood vessels, and on each is the nasopalatine groove, which runs obliquely downward and forward, and lodges the nasopalatine nerve and vessels. The superior border, the thickest, presents a deep furrow, bounded on either side by a horizontal projecting ala of bone; the furrow receives the rostrum of the sphenoid, while the margins of the alæ articulate with the vaginal processes of the medial pterygoid plates of the sphenoid behind, and with the sphenoidal processes of the palatine bones in front. The inferior border articulates with the crest formed by the maxillæ and palatine bones. The anterior border is the longest and slopes downward and forward. Its upper half is fused with the perpendicular plate of the ethmoid; its lower half is grooved for the inferior margin of the septal cartilage of the nose. The posterior border is free, concave, and separates the choanae. It is thick and bifid above, thin below. # Articulations The vomer articulates with six bones: - two of the cranium, the sphenoid and ethmoid. - four of the face, the two maxillae; and the two palatine bones. It also articulates with the septal cartilage of the nose. # Trivia By alternately thrusting with the tongue against the roof of the mouth and pressing with one of the fingers between the two eyebrows, one can articulate the vomer bone. This process, repeated for about 20 seconds, will cause the sinuses to discharge, thus rapidly clearing a stuffy head without the use of drugs.[1] # Additional images - Median wall of left nasal cavity showing vomer in situ. - The vomer. - Base of skull. Inferior surface. - The skull from the front. - Sagittal section of skull.	https://www.wikidoc.org/index.php/Vomer
29d818edcadd0a0ab7382b5bfaf524e61f5f026c	wikidoc	WASF1	WASF1 Wiskott-Aldrich syndrome protein family member 1, also known as WASP-family verprolin homologous protein 1 (WAVE1), is a protein that in humans is encoded by the WASF1 gene. # Function The protein encoded by this gene, a member of the Wiskott-Aldrich syndrome protein (WASP) family, plays a critical role downstream of Rac, a Rho-family small GTPase, through its involvement in the WAVE regulatory complex in regulating the actin cytoskeleton required for membrane ruffling. It has been shown to associate with an actin nucleation core Arp2/3 complex while enhancing actin polymerization in vitro. # Clinical significance Wiskott-Aldrich syndrome is a disease of the immune system, likely due to defects in regulation of actin cytoskeleton. # Interactions WASF1 has been shown to interact with BAIAP2 and Profilin 1.	WASF1 Wiskott-Aldrich syndrome protein family member 1, also known as WASP-family verprolin homologous protein 1 (WAVE1), is a protein that in humans is encoded by the WASF1 gene.[1][2][3] # Function The protein encoded by this gene, a member of the Wiskott-Aldrich syndrome protein (WASP) family, plays a critical role downstream of Rac, a Rho-family small GTPase, through its involvement in the WAVE regulatory complex in regulating the actin cytoskeleton required for membrane ruffling. It has been shown to associate with an actin nucleation core Arp2/3 complex while enhancing actin polymerization in vitro. # Clinical significance Wiskott-Aldrich syndrome is a disease of the immune system, likely due to defects in regulation of actin cytoskeleton.[3] # Interactions WASF1 has been shown to interact with BAIAP2[4] and Profilin 1.[1]	https://www.wikidoc.org/index.php/WASF1
53f2584e66ac9a4802236adf24809e0b9f33157d	wikidoc	WBP11	WBP11 # Alternative names - WW domain binding protein 11 (WBP11) - Npw38-binding protein (NpwBP) - Splicing factor that Interacts with PQBP-1 and PP1 (SIPP1) - SH3 domain binding Protein, 70 kDa (SNP70) # Function Studies suggest that Wbp11 plays a role in DNA/ RNA transcriptional or post-transcriptional events related to cell division. Wbp11 is found in the nucleus but not the nucleoli of cells in interphase. However it is distributed throughout the cytoplasm in dividing cells. Immunoelectron-microscopy experiments suggest that relocation from a peri-nuclear to a cytoplasmic distribution, coinciding with the onset of mitosis in cell division. Other studies have shown that Wbp11 is a component of the spliceosome. Also, that Wbp11 fragments block pre-mRNA splicing catalysis. # Protein interactions Wbp11 is a polypeptide known to interact with other WW domain of proteins such as the nuclear protein Npw38 via two proline-rich regions. It associates with Npw38 (hence the name NpwBP) in the nuclei and with Poly(rG) and G-rich ssDNA. The 70kDa protein has also been found to interact with SH3 (Src homology domain 3) domains. The C-terminal proline-rich sequences of SNP70/NpwBP/Wbp11, which binds to the WW domain of Npw38 also fits with both classic type I and type II SH3 binding sequences, hence the name (SNP70). Wbp11 was found to bind strongly to the tandem SH3 domains of p47phox and to the N-terminal SH3 domain of p47phox, and more weakly to the SH3 domains from c-src and p85α. p47phox. Furthermore, it has been shown to interact with PP1(protein phosphotase 1), hence the name SIPP1. It has an inhibitory effect to PP1, with its inhibitory potency increasing upon phosphorylation with protein kinase CK1. The binding of Wbp11 with PP1 involves a RVXF (Arg-Val-Xaa-Phe) motif, which functions as a PP1- binding sequence in most interactors of PP1. A number of other interactions have been indicated such as: - Vimentin - Growth factor receptor-bound protein 2 (GRB2) - Genome polyprotein - Tyrosine-protein kinase Fyn - Pre-mRNA-processing factor 39 (PRP39) - TNF receptor-associated factor 4 (TRAF4) - Calcineurin B homologous protein 3 (TESC) - Probable ATP-dependent RNA helicase DDX17 - CD2 antigen cytoplasmic tail-binding protein 2 (CD2BP2) - Poly(rC)-binding protein 1 (PCBP1)	WBP11 # Alternative names - WW domain binding protein 11 (WBP11) - Npw38-binding protein (NpwBP) - Splicing factor that Interacts with PQBP-1 and PP1 (SIPP1) - SH3 domain binding Protein, 70 kDa (SNP70) # Function Studies suggest that Wbp11 plays a role in DNA/ RNA transcriptional or post-transcriptional events related to cell division.[1] Wbp11 is found in the nucleus but not the nucleoli of cells in interphase. However it is distributed throughout the cytoplasm in dividing cells.[2] Immunoelectron-microscopy experiments suggest that relocation from a peri-nuclear to a cytoplasmic distribution, coinciding with the onset of mitosis in cell division. Other studies have shown that Wbp11 is a component of the spliceosome. Also, that Wbp11 fragments block pre-mRNA splicing catalysis.[3] # Protein interactions Wbp11 is a polypeptide known to interact with other WW domain of proteins such as the nuclear protein Npw38 via two proline-rich regions. It associates with Npw38 (hence the name NpwBP) in the nuclei and with Poly(rG) and G-rich ssDNA.[1] The 70kDa protein has also been found to interact with SH3 (Src homology domain 3) domains. The C-terminal proline-rich sequences of SNP70/NpwBP/Wbp11, which binds to the WW domain of Npw38 also fits with both classic type I and type II SH3 binding sequences, hence the name (SNP70). Wbp11 was found to bind strongly to the tandem SH3 domains of p47phox and to the N-terminal SH3 domain of p47phox, and more weakly to the SH3 domains from c-src and p85α. p47phox.[2] Furthermore, it has been shown to interact with PP1(protein phosphotase 1), hence the name SIPP1. It has an inhibitory effect to PP1, with its inhibitory potency increasing upon phosphorylation with protein kinase CK1. The binding of Wbp11 with PP1 involves a RVXF (Arg-Val-Xaa-Phe) motif, which functions as a PP1- binding sequence in most interactors of PP1.[3] A number of other interactions have been indicated such as: - Vimentin [2] - Growth factor receptor-bound protein 2 (GRB2) [4] - Genome polyprotein [5] - Tyrosine-protein kinase Fyn [4] - Pre-mRNA-processing factor 39 (PRP39) [6] - TNF receptor-associated factor 4 (TRAF4) [4] - Calcineurin B homologous protein 3 (TESC) [4] - Probable ATP-dependent RNA helicase DDX17 [7] - CD2 antigen cytoplasmic tail-binding protein 2 (CD2BP2) [8] - Poly(rC)-binding protein 1 (PCBP1) [9]	https://www.wikidoc.org/index.php/WBP11
0866872f85d79ee7226b1a7a3784a5d227b9e49f	wikidoc	WDR12	WDR12 Ribosome biogenesis protein WDR12 is a protein that in humans is encoded by the WDR12 gene on chromosome 2. It is ubiquitously expressed in many tissues and cell types. WDR12 participates in ribosome biogenesis and cell proliferation as a component of the PeboW complex. This protein is associated with cardiovascular diseases such as coronary artery disease and myocardial infarction. The PCSK9 gene also contains one of 27 loci associated with increased risk of coronary artery disease. # Structure ## Gene The WDR12 gene resides on chromosome 2 at the band 2q33.2 and includes 13 exons. ## Protein WDR12 is a member of the WD repeat WDR12/YTM1 family and contains 7 WD repeats. Each WD repeat typically contains a C-terminal tryptophan-aspartic acid dipeptide and an N-terminal glycine-histidine dipeptide. Disruption of these 7 WD repeats tampers with the predicted propeller-like structure formed and, consequently, its nucleolar localization. At the N-terminus of WDR12 lies a ubiquitin-like (UBL) domain, which contains β-grasp fold similar to that found in ubiquitin. The UBL domain binds the motor protein midasin and facilitates release of the PeBoW complex, which is composed of WDR12, Pescadillo 1 (PES1), and Block of proliferation 1 (BOP1), from pre-ribosomal particles. # Function The WDR12 gene is ubiquitously expressed during embryogenesis, and high levels are found in the thymus and testis of adult mice. It is a crucial factor in the mammalian ribosome biogenesis pathway that forms a stable complex named PeboW with Pes1 and Bop1. WDR12 is required for processing of the 32S precursor rRNA without affecting the synthesis of the 45S/47S primary transcript and it functions in the maturation of the 60S ribosomal subunit. Depletion of WDR12 severely inhibits cell proliferation. It is observed that WDR12 siRNA silencing in vitro resulted in decreased phosphorylation of p38 MAPK, HSP27, and ERK1/2 in neonatal myocytes, which may partially elucidate the mechanistic role of WDR12 in the regulation of cell proliferation, differentiation, and survival. Given the evidence of in vitro binding of WDR12 to the cytoplasmic domain of Notch1, it is postulated that WDR12 also functions in the modulation of Notch signaling activity. # Clinical significance In humans, a large genome-wide association study (GWAS) identified several single nucleotide polymorphisms (SNPs) that were reproducible and strongly associated with a risk for coronary artery disease and myocardial infarction (i.e., heart attacks). In this large genetic study, a total of 46 genomic loci were linked to variations in susceptibility to coronary artery disease. Within the 46 genome-wide SNPs, 12 indicated an association with a lipid levels and 5 showed significant association with high blood pressure. Accordingly, one of the most strongly associated variants was located on the WDR12 locus, which was also initially associated with the risk of early-onset myocardial infarction. However, its exact cellular and functional role in the heart is still being identified. ## Biomarker The expression of WDR12 in the rat heart and the human heart was studied using WDR12 gene delivery to examine the direct functional and structural effects of WDR12 on cardiac maladaptive remodeling, in particular the left ventricle. This recent study revealed that overexpression of WDR12 by gene delivery could deteriorate both systolic and diastolic function of the rat heart. Likewise, subsequent analysis of a cohort of 1400 human subjects corroborated that the WDR12 variant was associated with diastolic dysfunction. Additionally, a multi-locus genetic risk score study, based on a combination of 27 loci including the WDR12 gene, identified individuals at increased risk for both incidence and recurrent coronary artery disease events, as well as an enhanced clinical benefit from statin therapy. The study was based on a community cohort study (the Malmo Diet and Cancer study) and four additional randomized controlled trials of primary prevention cohorts (JUPITER and ASCOT) and secondary prevention cohorts (CARE and PROVE IT-TIMI 22). # Interactions ## Interactive Pathway Map WDR12 participates in interactions within the major pathway of rRNA processing in the nucleolus.	WDR12 Ribosome biogenesis protein WDR12 is a protein that in humans is encoded by the WDR12 gene on chromosome 2.[1][2][3] It is ubiquitously expressed in many tissues and cell types.[4] WDR12 participates in ribosome biogenesis and cell proliferation as a component of the PeboW complex.[1] This protein is associated with cardiovascular diseases such as coronary artery disease and myocardial infarction.[5] The PCSK9 gene also contains one of 27 loci associated with increased risk of coronary artery disease.[6] # Structure ## Gene The WDR12 gene resides on chromosome 2 at the band 2q33.2 and includes 13 exons.[3] ## Protein WDR12 is a member of the WD repeat WDR12/YTM1 family and contains 7 WD repeats.[7][1] Each WD repeat typically contains a C-terminal tryptophan-aspartic acid dipeptide and an N-terminal glycine-histidine dipeptide.[8] Disruption of these 7 WD repeats tampers with the predicted propeller-like structure formed and, consequently, its nucleolar localization.[1] At the N-terminus of WDR12 lies a ubiquitin-like (UBL) domain, which contains β-grasp fold similar to that found in ubiquitin. The UBL domain binds the motor protein midasin and facilitates release of the PeBoW complex, which is composed of WDR12, Pescadillo 1 (PES1), and Block of proliferation 1 (BOP1), from pre-ribosomal particles.[8][9] # Function The WDR12 gene is ubiquitously expressed during embryogenesis, and high levels are found in the thymus and testis of adult mice.[1] It is a crucial factor in the mammalian ribosome biogenesis pathway that forms a stable complex named PeboW with Pes1 and Bop1.[1][2] WDR12 is required for processing of the 32S precursor rRNA without affecting the synthesis of the 45S/47S primary transcript and it functions in the maturation of the 60S ribosomal subunit. Depletion of WDR12 severely inhibits cell proliferation.[2] It is observed that WDR12 siRNA silencing in vitro resulted in decreased phosphorylation of p38 MAPK, HSP27, and ERK1/2 in neonatal myocytes, which may partially elucidate the mechanistic role of WDR12 in the regulation of cell proliferation, differentiation, and survival.[10][11] Given the evidence of in vitro binding of WDR12 to the cytoplasmic domain of Notch1, it is postulated that WDR12 also functions in the modulation of Notch signaling activity.[12] # Clinical significance In humans, a large genome-wide association study (GWAS) identified several single nucleotide polymorphisms (SNPs) that were reproducible and strongly associated with a risk for coronary artery disease and myocardial infarction (i.e., heart attacks). In this large genetic study, a total of 46 genomic loci were linked to variations in susceptibility to coronary artery disease.[13] Within the 46 genome-wide SNPs, 12 indicated an association with a lipid levels and 5 showed significant association with high blood pressure. Accordingly, one of the most strongly associated variants was located on the WDR12 locus, which was also initially associated with the risk of early-onset myocardial infarction.[13] However, its exact cellular and functional role in the heart is still being identified. ## Biomarker The expression of WDR12 in the rat heart and the human heart was studied using WDR12 gene delivery to examine the direct functional and structural effects of WDR12 on cardiac maladaptive remodeling, in particular the left ventricle. This recent study revealed that overexpression of WDR12 by gene delivery could deteriorate both systolic and diastolic function of the rat heart. Likewise, subsequent analysis of a cohort of 1400 human subjects corroborated that the WDR12 variant was associated with diastolic dysfunction.[8] Additionally, a multi-locus genetic risk score study, based on a combination of 27 loci including the WDR12 gene, identified individuals at increased risk for both incidence and recurrent coronary artery disease events, as well as an enhanced clinical benefit from statin therapy. The study was based on a community cohort study (the Malmo Diet and Cancer study) and four additional randomized controlled trials of primary prevention cohorts (JUPITER and ASCOT) and secondary prevention cohorts (CARE and PROVE IT-TIMI 22).[6] # Interactions ## Interactive Pathway Map WDR12 participates in interactions within the major pathway of rRNA processing in the nucleolus.	https://www.wikidoc.org/index.php/WDR12
f2f8ca20b3eb6df5a872fd8deb6c1703e754861e	wikidoc	WDR45	WDR45 WD repeat domain phosphoinositide-interacting protein 4 (WIPI-4) is a protein that in humans is encoded by the WDR45 gene. Mutations in this gene cause a distinct form of Neurodegeneration with brain iron accumulation (NBIA). # Function WIPI-4 is a member of the WD repeat protein family. WD repeats are minimally conserved regions of approximately 40 amino acids typically bracketed by gly-his and trp-asp (GH-WD), which may facilitate formation of heterotrimeric or multiprotein complexes. Members of this family are involved in a variety of cellular processes, including cell cycle progression, signal transduction, apoptosis, and gene regulation. This gene WDR45 has a pseudogene at chromosome 4q31.3. Multiple alternatively spliced transcript variants encoding distinct isoforms have been found for this gene, but the biological validity and full-length nature of some variants have not been determined. # Role in Disease De novo loss of function mutations in WDR45 were identified by exome sequencing in 20 patients with NBIA. The mutations cause an X-linked dominant form of NBIA now called Beta-propeller protein-associated neurodegeneration (BPAN).	WDR45 WD repeat domain phosphoinositide-interacting protein 4 (WIPI-4) is a protein that in humans is encoded by the WDR45 gene.[1][2] Mutations in this gene cause a distinct form of Neurodegeneration with brain iron accumulation (NBIA).[3] # Function WIPI-4 is a member of the WD repeat protein family. WD repeats are minimally conserved regions of approximately 40 amino acids typically bracketed by gly-his and trp-asp (GH-WD), which may facilitate formation of heterotrimeric or multiprotein complexes. Members of this family are involved in a variety of cellular processes, including cell cycle progression, signal transduction, apoptosis, and gene regulation. This gene WDR45 has a pseudogene at chromosome 4q31.3. Multiple alternatively spliced transcript variants encoding distinct isoforms have been found for this gene, but the biological validity and full-length nature of some variants have not been determined.[2] # Role in Disease De novo loss of function mutations in WDR45 were identified by exome sequencing in 20 patients with NBIA.[3] The mutations cause an X-linked dominant form of NBIA now called Beta-propeller protein-associated neurodegeneration (BPAN).[3]	https://www.wikidoc.org/index.php/WDR45
e5a3c46ac7bad132e67ee0772085e0afee4a0a0c	wikidoc	WDR47	WDR47 WD repeat domain 47 is a protein that in humans is encoded by the WDR47 gene. # Model organisms Model organisms have been used in the study of WDR47 function. A conditional knockout mouse line, called Wdr47tm1a(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-six tests were carried out on mutant mice and three significant abnormalities were observed. Homozygous mutant animals had an absence of corpus callosum and increased circulating alkaline phosphatase levels. Male homozygous mice also had abnormal indirect calorimetry measures.	WDR47 WD repeat domain 47 is a protein that in humans is encoded by the WDR47 gene.[1] # Model organisms Model organisms have been used in the study of WDR47 function. A conditional knockout mouse line, called Wdr47tm1a(EUCOMM)Wtsi[7][8] was generated as part of the International Knockout Mouse Consortium program — a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists.[9][10][11] Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion.[5][12] Twenty-six tests were carried out on mutant mice and three significant abnormalities were observed.[5] Homozygous mutant animals had an absence of corpus callosum and increased circulating alkaline phosphatase levels. Male homozygous mice also had abnormal indirect calorimetry measures.[5]	https://www.wikidoc.org/index.php/WDR47
8af5cf0dd3d8d83dfd4abf3e845ac28ea1189451	wikidoc	WDR62	WDR62 WD repeat-containing protein 62 is a protein that in humans is encoded by the WDR62 gene. # Clinical relevance Mutations in the WDR62 gene cause of a wide spectrum of severe cerebral cortical malformations including microcephaly, pachygyria with cortical thickening, hypoplasia of the corpus callosum, polymicrogyria as well as microlissencephaly. In 2018 Xu et al showed that WDR62 stability and neurogenesis is regulated by MEKK3 in coordination with FBW7 (F-box and WD repeat domain-containing protein 7).	WDR62 WD repeat-containing protein 62 is a protein that in humans is encoded by the WDR62 gene.[1][2] # Clinical relevance Mutations in the WDR62 gene cause of a wide spectrum of severe cerebral cortical malformations including microcephaly,[3] pachygyria with cortical thickening, hypoplasia of the corpus callosum[1], polymicrogyria as well as microlissencephaly.[4] In 2018 Xu et al showed that WDR62 stability and neurogenesis is regulated by MEKK3 in coordination with FBW7 (F-box and WD repeat domain-containing protein 7).[5]	https://www.wikidoc.org/index.php/WDR62
685c7a8d2f2a8ae6812626a23ea5ff12b5e534b5	wikidoc	WFDC2	WFDC2 WAP four-disulfide core domain protein 2 - also known as Human Epididymis Protein 4 (HE4) - is a protein that in humans is encoded by the WFDC2 gene. HE4 is a tumor marker of ovarian cancer, with 80% sensitivity at a cut-off of 150 pmol/L. # Function This gene encodes a protein that is a member of the WFDC domain family. The WFDC domain, or WAP Signature motif, contains eight cysteines forming four disulfide bonds at the core of the protein, and functions as a protease inhibitor in many family members. This gene is expressed in pulmonary epithelial cells, and was also found to be expressed in some ovarian cancers. The encoded protein is a small secretory protein, which may be involved in sperm maturation.	WFDC2 WAP four-disulfide core domain protein 2 - also known as Human Epididymis Protein 4[1] (HE4) - is a protein that in humans is encoded by the WFDC2 gene.[2][3][4] HE4 is a tumor marker of ovarian cancer, with 80% sensitivity at a cut-off of 150 pmol/L.[5] # Function This gene encodes a protein that is a member of the WFDC domain family. The WFDC domain, or WAP Signature motif, contains eight cysteines forming four disulfide bonds at the core of the protein, and functions as a protease inhibitor in many family members. This gene is expressed in pulmonary epithelial cells, and was also found to be expressed in some ovarian cancers.[1] The encoded protein is a small secretory protein, which may be involved in sperm maturation.[4]	https://www.wikidoc.org/index.php/WFDC2
714bf719b955a9b406e9816cedbf87eeff9de86d	wikidoc	WIPF1	WIPF1 WAS/WASL-interacting protein family member 1 (WIP) is a protein that in humans is encoded by the WIPF1 gene. # Function This gene encodes a protein that plays an important role in the organization of the actin cytoskeleton. Overexpression of WIP in mammalian cells has been shown to increase actin polymerization. The encoded protein binds to a region of Wiskott-Aldrich syndrome protein that is frequently mutated in Wiskott-Aldrich syndrome, an X-linked recessive disorder. Impairment of the interaction between these two proteins may contribute to the disease. Two transcript variants encoding the same protein have been identified for this gene. In patients lacking the WIPF1 gene WASp protein levels are depleted and WAS symptoms present. # Interactions WIPF1 has been shown to interact with Wiskott-Aldrich syndrome protein, Cortactin, NCK1, and ITSN1. While Wiskott-Aldrich syndrome protein is expressed only in haematopoetic cells, WIPF1 is expressed ubiquitously. Majority of the mutations causing Wiskott Aldrich Syndrome are located in the WH1 domain of WASp. These mutations affect WASp-WIPF1 binding. WIPF1 yeast homologue verprolin Vrp1 binds class 1 myosin and enhances class 1 myosin dependent actin nucleation. WIPF1 has an N-terminal profilin binding domain, two actin binding WH2 domains, a central polyproline stretch, and a C-terminal WASP Binding Domain.	WIPF1 WAS/WASL-interacting protein family member 1 (WIP) is a protein that in humans is encoded by the WIPF1 gene.[1][2] # Function This gene encodes a protein that plays an important role in the organization of the actin cytoskeleton. Overexpression of WIP in mammalian cells has been shown to increase actin polymerization.[1] The encoded protein binds to a region of Wiskott-Aldrich syndrome protein that is frequently mutated in Wiskott-Aldrich syndrome, an X-linked recessive disorder. Impairment of the interaction between these two proteins may contribute to the disease. Two transcript variants encoding the same protein have been identified for this gene.[2] In patients lacking the WIPF1 gene WASp protein levels are depleted and WAS symptoms present.[3] # Interactions WIPF1 has been shown to interact with Wiskott-Aldrich syndrome protein,[1][4] Cortactin[5], NCK1[4], and ITSN1[6]. While Wiskott-Aldrich syndrome protein is expressed only in haematopoetic cells, WIPF1 is expressed ubiquitously[1]. Majority of the mutations causing Wiskott Aldrich Syndrome are located in the WH1 domain of WASp.[7] These mutations affect WASp-WIPF1 binding.[8] WIPF1 yeast homologue verprolin Vrp1 binds class 1 myosin and enhances class 1 myosin dependent actin nucleation.[9] WIPF1 has an N-terminal profilin binding domain, two actin binding WH2 domains, a central polyproline stretch, and a C-terminal WASP Binding Domain.	https://www.wikidoc.org/index.php/WIPF1
ed55a9d50b901bbfcdf6faee6584f86696bd3c49	wikidoc	WIPI2	WIPI2 WD repeat domain phosphoinositide-interacting protein 2 is a protein that in humans is encoded by the WIPI2 gene. # Function WD40 repeat proteins are key components of many essential biologic functions. They regulate the assembly of multiprotein complexes by presenting a beta-propeller platform for simultaneous and reversible protein-protein interactions. Members of the WIPI subfamily of WD40 repeat proteins, such as WIPI2, have a 7-bladed propeller structure and contain a conserved motif for interaction with phospholipids. WIPI2 is the mammalian homolog of Atg18, not Atg21, along with the closely related protein, WIPI1. WIPI2 mRNA is readily detectable in several commonly used laboratory cell lines (HEK293A, HeLa, A431) and several cancer cell lines, while WIPI1 expression is limited to cancer cells. The Atg proteins regulate autophagy, which is a lysosomal degradation pathway required for maintaining cell health, surviving periods of nutrient deprivation and also plays a role in cancer, neurodegeneration and immune responses to a diverse range of pathogens. WIPI2 is recruited early to the forming autophagosome, along with DFCP-1, ULK-1 and Atg16, where it positively regulates the lipidation of Atg8 (LC3). This is not true for WIPI1.	WIPI2 WD repeat domain phosphoinositide-interacting protein 2 is a protein that in humans is encoded by the WIPI2 gene.[1][2] # Function WD40 repeat proteins are key components of many essential biologic functions. They regulate the assembly of multiprotein complexes by presenting a beta-propeller platform for simultaneous and reversible protein-protein interactions. Members of the WIPI subfamily of WD40 repeat proteins, such as WIPI2, have a 7-bladed propeller structure and contain a conserved motif for interaction with phospholipids.[1][2] WIPI2 is the mammalian homolog of Atg18, not Atg21, along with the closely related protein, WIPI1. WIPI2 mRNA is readily detectable in several commonly used laboratory cell lines (HEK293A, HeLa, A431) and several cancer cell lines, while WIPI1 expression is limited to cancer cells. The Atg proteins regulate autophagy, which is a lysosomal degradation pathway required for maintaining cell health, surviving periods of nutrient deprivation and also plays a role in cancer, neurodegeneration and immune responses to a diverse range of pathogens.[3] WIPI2 is recruited early to the forming autophagosome, along with DFCP-1, ULK-1 and Atg16, where it positively regulates the lipidation of Atg8 (LC3). This is not true for WIPI1.	https://www.wikidoc.org/index.php/WIPI2
9f1c55932c1cb0bb8e30eed8c1171cd422249e73	wikidoc	WNT16	WNT16 Protein Wnt-16 is a protein that in humans is encoded by the WNT16 gene. It has been proposed that stimulation of WNT16 expression in nearby normal cells is responsible for the development of chemotherapy-resistance in cancer cells. # Function The WNT gene family consists of structurally related genes that encode secreted signaling proteins. These proteins have been implicated in oncogenesis and in several developmental processes, including regulation of cell fate and patterning during embryogenesis. This gene is a member of the WNT gene family. It contains two transcript variants diverging at the 5' termini. These two variants are proposed to be the products of separate promoters and not to be splice variants from a single promoter. They are differentially expressed in normal tissues, one of which (variant 2) is expressed at significant levels only in the pancreas, whereas another one (variant 1) is expressed more ubiquitously with highest levels in adult kidney, placenta, brain, heart, and spleen. WNT16B expression is regulated by nuclear factor of κ light polypeptide gene enhancer in B cells 1 (NF-κB) after DNA damage, as can occur to normal cells during radiation or chemotherapy. Subsequently WNT16B signals in a paracrine manner to activate the Wnt expression program in tumor cells. The expression of WNT16B in the tumor microenvironment attenuates the effects of cytotoxic chemotherapy in vivo, promoting tumor cell survival and disease progression. This implies a mechanism by which cycles of genotoxic therapy might enhance subsequent treatment resistance in the tumor microenvironment. # Model organisms Model organisms have been used in the study of WNT16 function. A conditional knockout mouse line called Wnt16tm2b(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	WNT16 Protein Wnt-16 is a protein that in humans is encoded by the WNT16 gene.[1][2] It has been proposed that stimulation of WNT16 expression in nearby normal cells is responsible for the development of chemotherapy-resistance in cancer cells.[3] # Function The WNT gene family consists of structurally related genes that encode secreted signaling proteins. These proteins have been implicated in oncogenesis and in several developmental processes, including regulation of cell fate and patterning during embryogenesis. This gene is a member of the WNT gene family. It contains two transcript variants diverging at the 5' termini. These two variants are proposed to be the products of separate promoters and not to be splice variants from a single promoter. They are differentially expressed in normal tissues, one of which (variant 2) is expressed at significant levels only in the pancreas, whereas another one (variant 1) is expressed more ubiquitously with highest levels in adult kidney, placenta, brain, heart, and spleen.[2] WNT16B expression is regulated by nuclear factor of κ light polypeptide gene enhancer in B cells 1 (NF-κB) after DNA damage, as can occur to normal cells during radiation or chemotherapy. Subsequently WNT16B signals in a paracrine manner to activate the Wnt expression program in tumor cells. The expression of WNT16B in the tumor microenvironment attenuates the effects of cytotoxic chemotherapy in vivo, promoting tumor cell survival and disease progression. This implies a mechanism by which cycles of genotoxic therapy might enhance subsequent treatment resistance in the tumor microenvironment.[3] # Model organisms Model organisms have been used in the study of WNT16 function. A conditional knockout mouse line called Wnt16tm2b(EUCOMM)Wtsi was generated at the Wellcome Trust Sanger Institute.[4] Male and female animals underwent a standardized phenotypic screen[5] to determine the effects of deletion.[6][7][8][9] Additional screens performed: - In-depth immunological phenotyping[10] - in-depth bone and cartilage phenotyping[11]	https://www.wikidoc.org/index.php/WNT16
30450127dd373d49e5a2bbbe83c3a70cd8741490	wikidoc	WNT5A	WNT5A Protein Wnt-5a is a protein that in humans is encoded by the WNT5A gene. # Function The WNT gene family consists of structurally related genes that encode secreted signaling lipid modified glycoproteins. These proteins have been implicated in oncogenesis and in several developmental processes, including regulation of cell fate and patterning during embryogenesis. This gene is a member of the WNT gene family. The WNT5A is highly expressed in the dermal papilla of depilated skin. It encodes a protein showing 98%, 98%, and 87% amino acid identity to the mouse, rat and the xenopus Wnt5a protein, respectively. Wnts, specifically Wnt5a, have also been positively correlated and implicated in inflammatory diseases such as rheumatoid arthritis, tuberculosis, and atherosclerosis. A central player and active secretor of Wnt5a in both cancer and these inflammatory diseases are macrophages. Experiments performed in Xenopus laevis embryos have identified that human frizzled-5 (hFz5) is the receptor for the Wnt5a ligand and the Wnt5a/hFz5 signaling mediates axis induction. However, non-canonical Wnt5a has also been shown to bind to Ror1/2, RYK, and RTK depending on cell and receptor context to mediate a variety of functions ranging from cell proliferation, polarity, differentiation and apoptosis. ## Development The Wnt5a gene is also a key component in posterior development of the female reproductive tract, development of the uterine glands postnatally, and the process of estrogen mediated cellular and molecular responses. Wnt5a is expressed throughout the endometrial stroma of the mammalian female reproductive tracts and is required in the development of the posterior formation of the Müllerian ducts (cervix, vagina). A Wnt5a absence study was performed by Mericskay et al. on mice and showed the anterior Müllerian-derived structures (oviducts and uterine horns) could easily be identified, and the posterior derived structures (cervix and vagina) were absent showing that this gene is a requirement for its development. Other members of the WNT family that are required for the development of the reproductive tract are Wnt4 and Wnt7a. Failure to develop reproductive tract will result in infertility. Not only is the WNT5A gene responsible for this formation but also is significate in the postnatal production of the uterine glands otherwise known as adenogenesis which is essential for adult function. In addition to these two developments Wnt5a it needed for the complete process of estrogen mediated cellular and molecular responses. # Wnt ligands Wnt ligands are classically described as acting in an autocrine/paracrine manner. Wnts are also hydrophobic with significant post-translational palmitoylation and glycosylation. These post-translational modifications are important for docking to extracellular lipoprotein particles allowing them to travel systemically. Additionally, due to the high degree of sequence homology between Wnts many are characterized by their downstream actions. # Clinical significance ## Cancer Wnt5a is implicated in many different types of cancers. However, no consistent correlation occurs between cancer aggressiveness and Wnt5a signaling up-regulation or down-regulation. The WNT5A gene has been shown to encode two distinct isoforms, each with unique functions in the context of cancer. The two isoforms are termed Wnt5a-long (Wnt5a-L) and Wnt5a-short (Wnt5a-S) because Wnt5a-L is 18 amino acids longer than Wnt5a-S. These 18 amino acids appear to have contrasting roles in cancer. Specifically, Wnt5a-L inhibits proliferation and Wnt5a-S increases proliferation. This may account for the discrepancies as to the role of Wnt5a in various cancers; however, the significance of these two isoforms is not completely clear. Elevated levels of beta-catenin in both primary and metastases of malignant melanoma have been correlated to improved survival and a decrease in cell markers of proliferation. ## Cardiovascular Disease Increasing evidence has implicated Wnt5a in chronic inflammatory disorders. In particular Wnt5a has been implicated in atherosclerosis. It has been previously reported that there is an association between Wnt5a mRNA and protein expression and histopathological severity of human atherosclerotic lesions as well as co-expression of Wnt5a and TLR4 in foam cells/macrophages of murine and human atherosclerotic lesions. However, the role of Wnt proteins in the process and development of inflammation in atherosclerosis and other inflammatory conditions is not yet clear. ## Therapeutics Some of the benefits of targeting this signaling pathway include: - Many of the current DNA-targeting anticancer drugs carry the risk of giving rise to secondary tumors or additional primary cancers. - Preferentially killing rapidly replicating malignant cells via cytotoxic agents cause serious side effects by injuring normal cells, particularly hematopoeitic cells, intestinal cells, hair follicle and germ cells. - Differentiated tumor cells in a state of quiescence are typically not affected by drugs can may account for tumor recurrence.	WNT5A Protein Wnt-5a is a protein that in humans is encoded by the WNT5A gene.[1][2] # Function The WNT gene family consists of structurally related genes that encode secreted signaling lipid modified glycoproteins. These proteins have been implicated in oncogenesis and in several developmental processes, including regulation of cell fate and patterning during embryogenesis.[3] This gene is a member of the WNT gene family. The WNT5A is highly expressed in the dermal papilla of depilated skin. It encodes a protein showing 98%, 98%, and 87% amino acid identity to the mouse, rat and the xenopus Wnt5a protein, respectively. Wnts, specifically Wnt5a, have also been positively correlated and implicated in inflammatory diseases such as rheumatoid arthritis, tuberculosis, and atherosclerosis. A central player and active secretor of Wnt5a in both cancer and these inflammatory diseases are macrophages.[4][5] Experiments performed in Xenopus laevis embryos have identified that human frizzled-5 (hFz5) is the receptor for the Wnt5a ligand and the Wnt5a/hFz5 signaling mediates axis induction.[2] However, non-canonical Wnt5a has also been shown to bind to Ror1/2, RYK, and RTK depending on cell and receptor context to mediate a variety of functions ranging from cell proliferation, polarity, differentiation and apoptosis.[6][7] ## Development The Wnt5a gene is also a key component in posterior development of the female reproductive tract, development of the uterine glands postnatally, and the process of estrogen mediated cellular and molecular responses.[8] Wnt5a is expressed throughout the endometrial stroma of the mammalian female reproductive tracts and is required in the development of the posterior formation of the Müllerian ducts (cervix, vagina).[9] A Wnt5a absence study was performed by Mericskay et al. on mice and showed the anterior Müllerian-derived structures (oviducts and uterine horns) could easily be identified, and the posterior derived structures (cervix and vagina) were absent showing that this gene is a requirement for its development.[8] Other members of the WNT family that are required for the development of the reproductive tract are Wnt4 and Wnt7a.[9] Failure to develop reproductive tract will result in infertility. Not only is the WNT5A gene responsible for this formation but also is significate in the postnatal production of the uterine glands otherwise known as adenogenesis which is essential for adult function.[8] In addition to these two developments Wnt5a it needed for the complete process of estrogen mediated cellular and molecular responses.[8] # Wnt ligands Wnt ligands are classically described as acting in an autocrine/paracrine manner.[10][11][12] Wnts are also hydrophobic with significant post-translational palmitoylation and glycosylation.[13][14] These post-translational modifications are important for docking to extracellular lipoprotein particles allowing them to travel systemically.[15][16] Additionally, due to the high degree of sequence homology between Wnts many are characterized by their downstream actions. # Clinical significance ## Cancer Wnt5a is implicated in many different types of cancers.[17] However, no consistent correlation occurs between cancer aggressiveness and Wnt5a signaling up-regulation or down-regulation. The WNT5A gene has been shown to encode two distinct isoforms, each with unique functions in the context of cancer.[18] The two isoforms are termed Wnt5a-long (Wnt5a-L) and Wnt5a-short (Wnt5a-S) because Wnt5a-L is 18 amino acids longer than Wnt5a-S.[18] These 18 amino acids appear to have contrasting roles in cancer. Specifically, Wnt5a-L inhibits proliferation and Wnt5a-S increases proliferation.[18] This may account for the discrepancies as to the role of Wnt5a in various cancers; however, the significance of these two isoforms is not completely clear.[19] Elevated levels of beta-catenin in both primary and metastases of malignant melanoma have been correlated to improved survival and a decrease in cell markers of proliferation.[20] ## Cardiovascular Disease Increasing evidence has implicated Wnt5a in chronic inflammatory disorders.[21] In particular Wnt5a has been implicated in atherosclerosis.[22] It has been previously reported that there is an association between Wnt5a mRNA and protein expression and histopathological severity of human atherosclerotic lesions as well as co-expression of Wnt5a and TLR4 in foam cells/macrophages of murine and human atherosclerotic lesions.[23][24] However, the role of Wnt proteins in the process and development of inflammation in atherosclerosis and other inflammatory conditions is not yet clear. ## Therapeutics Some of the benefits of targeting this signaling pathway include:[25] • Many of the current DNA-targeting anticancer drugs carry the risk of giving rise to secondary tumors or additional primary cancers. • Preferentially killing rapidly replicating malignant cells via cytotoxic agents cause serious side effects by injuring normal cells, particularly hematopoeitic cells, intestinal cells, hair follicle and germ cells. • Differentiated tumor cells in a state of quiescence are typically not affected by drugs can may account for tumor recurrence.	https://www.wikidoc.org/index.php/WNT5A
dba0871dfc342cb05751e2a6e5a35fc6c73bc738	wikidoc	WWTR1	WWTR1 WW domain-containing transcription regulator protein 1 is a protein that in humans is encoded by the WWTR1 gene. # Function WWTR1 It is a transcriptional coactivator which acts as a downstream regulatory target in the Hippo signaling pathway that plays a pivotal role in organ size control and tumor suppression by restricting proliferation and promoting apoptosis. The core of this pathway is composed of a kinase cascade wherein MST1/MST2, in complex with its regulatory protein SAV1, phosphorylates and activates LATS1/LATS2 in complex with its regulatory protein MOB1, which in turn phosphorylates and inactivates YAP1 oncoprotein and WWTR1/TAZ. WWTR1 enhances PAX8 and NKX2-1/TTF1-dependent gene activation. Regulates the nuclear accumulation of SMADs and has a key role in coupling them to the transcriptional machinery such as the mediator complex. Using the human SHSY5Y cell line as a model of neuronal differentiation, human FAT1 was shown to regulate the nucleocytoplasmic relocation of WWTR1/TAZ and enhanced transcription of the Hippo target gene CTGF. The same study also showed FAT1 was able to regulate TGF-beta signalling	WWTR1 WW domain-containing transcription regulator protein 1 is a protein that in humans is encoded by the WWTR1 gene.[1][2][3] # Function WWTR1 It is a transcriptional coactivator which acts as a downstream regulatory target in the Hippo signaling pathway that plays a pivotal role in organ size control and tumor suppression by restricting proliferation and promoting apoptosis. The core of this pathway is composed of a kinase cascade wherein MST1/MST2, in complex with its regulatory protein SAV1, phosphorylates and activates LATS1/LATS2 in complex with its regulatory protein MOB1, which in turn phosphorylates and inactivates YAP1 oncoprotein and WWTR1/TAZ. WWTR1 enhances PAX8 and NKX2-1/TTF1-dependent gene activation. Regulates the nuclear accumulation of SMADs and has a key role in coupling them to the transcriptional machinery such as the mediator complex. Using the human SHSY5Y cell line as a model of neuronal differentiation, human FAT1 was shown to regulate the nucleocytoplasmic relocation of WWTR1/TAZ and enhanced transcription of the Hippo target gene CTGF. The same study also showed FAT1 was able to regulate TGF-beta signalling [4]	https://www.wikidoc.org/index.php/WWTR1
cc12d18f4d92d2b10812d82d5fe939e5bb855a35	wikidoc	WebMD	WebMD WebMD is a medical and wellness information service, primarily known for its public internet site, which provides health information, a symptom checklist, pharmacy information, a place to store personal medical information, and an online community with over 140 moderated expert-led and peer-to-peer message boards. The site is reported to receive over 40 million hits each month and is the leading health portal in the nation according to comScore Media Metrix. WebMD also offers services to physicians and private clients. For example, they publish WebMD the Magazine, a patient-directed publication distributed bimonthly to 85 percent of physician waiting rooms.. Medscape is a professional portal for physicians with 30 medical specialty areas and over 30 physician discussion boards. WebMD owns several other medically-related internet sites including WebMD Health, Medscape, MedicineNet, eMedicine, eMedicine Health, RxList and theheart.org. The organization is financed by third-party contributions and sponsorships.	WebMD WebMD is a medical and wellness information service, primarily known for its public internet site, which provides health information, a symptom checklist, pharmacy information, a place to store personal medical information, and an online community with over 140 moderated expert-led and peer-to-peer message boards.[1] The site is reported to receive over 40 million hits each month[2] [3] and is the leading health portal in the nation according to comScore Media Metrix. WebMD also offers services to physicians and private clients. For example, they publish WebMD the Magazine, a patient-directed publication distributed bimonthly to 85 percent of physician waiting rooms.[citation needed]. Medscape is a professional portal for physicians with 30 medical specialty areas and over 30 physician discussion boards. WebMD owns several other medically-related internet sites including WebMD Health, Medscape, MedicineNet, eMedicine, eMedicine Health, RxList and theheart.org. The organization is financed by third-party contributions and sponsorships.[4]	https://www.wikidoc.org/index.php/WebMD
87d14ddd95aad8b4dc738ae53e594ad33c2b7d49	wikidoc	Wheat	Wheat Wheat (Triticum spp.) is a grass that is cultivated worldwide. Globally, it is an important human food grain ranking second in total production as a cereal crop behind maize; the third being rice. Wheat grain is a staple food used to make flour for leavened, flat and steamed breads; cookies, cakes, pasta, noodles and couscous; and for fermentation to make beer, alcohol, vodka or biofuel. Wheat is planted to a limited extent as a forage crop for livestock, and the straw can be used as fodder for livestock or as a construction material for roofing thatch. # History Wheat originated in Southwest Asia in the area known as the Fertile Crescent. The genetic relationships between einkorn and emmer indicate that the most likely site of domestication is near Diyarbakır in Turkey . These wild wheats were domesticated as part of the origins of agriculture in the Fertile Crescent. Cultivation and repeated harvesting and sowing of the grains of wild grasses led to the domestication of wheat through selection of mutant forms with tough ears which remained intact during harvesting, larger grains, and a tendency for the spikelets to stay on the stalk until harvested . Because of the loss of seed dispersal mechanisms, domesticated wheats have limited capacity to propagate in the wild. The cultivation of wheat began to spread beyond the Fertile Crescent during the Neolithic period. By 5,000 years ago, wheat had reached Ethiopia, India, Ireland and Spain. A millennium later it reached China. Three thousand years ago agricultural cultivation with horse drawn plows increased cereal grain production, as did the use of seed drills to replace broadcast sowing in the 18th century. Yields of wheat continued to increase, as new land came under cultivation and with improved agricultural husbandry involving the use of fertilizers, threshing machines and reaping machines (the 'combine harvester'), tractor-drawn cultivators and planters, and better varieties (see green revolution and Norin 10 wheat). With population growth rates falling, while yields continue to rise, the area devoted to wheat may now begin to decline for the first time in modern human history. But now in 2007 wheat stocks have reached their lowest since 1981, and 2006 was the first year in which the world consumed more wheat than the world produced - a gap that is continuously widening as the requirement for wheat increases beyond production. The use of wheat as a bio-fuel will exacerbate the situation. # Genetics Wheat genetics is more complicated than that of most other domesticated species. Some wheat species are diploid, with two sets of chromosomes, but many are stable polyploids, with four sets of chromosomes (tetraploid) or six (hexaploid). - Einkorn wheat (T. monococcum) is diploid. - Most tetraploid wheats (e.g. emmer and durum wheat) are derived from wild emmer, T. dicoccoides. Wild emmer is the result of a hybridization between two diploid wild grasses, T. urartu and a wild goatgrass such as Aegilops searsii or Ae. speltoides. The hybridization that formed wild emmer occurred in the wild, long before domestication. - Hexaploid wheats evolved in farmers' fields. Either domesticated emmer or durum wheat hybridized with yet another wild diploid grass (Aegilops tauschii) to make the hexaploid wheats, spelt wheat and bread wheat. # Plant Breeding In traditional agricultural systems wheat is often grown as landraces, informal farmer-maintained populations that often maintain high levels of morophological diversity. Although landraces of wheat are no longer grown in Europe and North America, they continue to be important elsewhere. The origins of formal wheat breeding lie in the nineteenth century, when single line varieties were created through selection of seed from a single plant noted to have desired properties. Modern wheat breeding developed in the first years of the twentieth century and was closely linked to the development of Mendelian genetics. The standard method of breeding inbred wheat cultivars is by crossing two lines using hand emasculation, then selfing or inbreeding the progeny. Selections are identified (shown to have the genes responsible for the varietal differences) ten or more generations before release as a variety or cultivar. F1 hybrid wheat cultivars should not be confused with wheat cultivars deriving from standard plant breeding. Heterosis or hybrid vigor (as in the familiar F1 hybrids of maize) occurs in common (hexaploid) wheat, but it is difficult to produce seed of hybrid cultivars on a commercial scale as is done with maize because wheat flowers are complete and normally self-pollinate. Commercial hybrid wheat seed has been produced using chemical hybridizing agents, plant growth regulators that selectively interfere with pollen development, or naturally occurring cytoplasmic male sterility systems. Hybrid wheat has been a limited commercially success, in Europe (particularly France), the USA and South Africa. # Hulled versus free-threshing wheat The four wild species of wheat, along with the domesticated varieties einkorn, emmer and spelt, have hulls (in German, Spelzweizen). This more primitive morphology consists of toughened glumes that tightly enclose the grains, and (in domesticated wheats) a semi-brittle rachis that breaks easily on threshing. The result is that when threshed, the wheat ear breaks up into spikelets. To obtain the grain, further processing, such as milling or pounding, is needed to remove the hulls or husks. In contrast, in free-threshing (or naked) forms such as durum wheat and common wheat, the glumes are fragile and the rachis tough. On threshing, the chaff breaks up, releasing the grains. Hulled wheats are often stored as spikelets because the toughened glumes give good protection against pests of stored grain. # Naming There are many botanical classification systems used for wheat species, discussed in a separate article on Wheat taxonomy. The name of a wheat species from one information source may not be the name of a wheat species in another. Within a species, wheat cultivars are further classified by wheat breeders and farmers in terms of growing season, such as winter wheat vs. spring wheat, by gluten content, such as hard wheat (high protein content) vs. soft wheat (high starch content), or by grain color (red, white or amber). ## Major cultivated species of wheat - Common wheat or Bread wheat — (T. aestivum) A hexaploid species that is the most widely cultivated in the world. - Durum — (T. durum) The only tetraploid form of wheat widely used today, and the second most widely cultivated wheat. - Einkorn — (T. monococcum) A diploid species with wild and cultivated variants. Domesticated at the same time as emmer wheat, but never reached the same importance. - Emmer — (T. dicoccon) A tetraploid species, cultivated in ancient times but no longer in widespread use. - Spelt — (T. spelta) Another hexaploid species cultivated in limited quantities. # Economics Harvested wheat grain that enters trade is classified according to grain properties (see below) for the purposes of the commodities market. Wheat buyers use the classifications to help determine which wheat to purchase as each class has special uses. Wheat producers determine which classes of wheat are the most profitable to cultivate with this system. Wheat is widely cultivated as a cash crop because it produces a good yield per unit area, grows well in a temperate climate even with a moderately short growing season, and yields a versatile, high-quality flour that is widely used in baking. Most breads are made with wheat flour, including many breads named for the other grains they contain like most rye and oat breads. Many other popular foods are made from wheat flour as well, resulting in a large demand for the grain even in economies with a significant food surplus. In 2007 there was a dramatic rise in the price of wheat due to freezes and flooding in the northern hemisphere and a drought in Australia. Wheat futures in September, 2007 for December and March delivery had risen above $9.00 a bushel, prices never seen before. There were complaints in Italy about the high price of pasta. # Production and consumption statistics In 1997, global per capita wheat consumption was 101 kg, with the highest per capita consumption (623 kg) found in Denmark. See also International wheat production statistics. Unlike rice, wheat production is more widespread globally though China's share is almost one-sixth of the world. # Agronomy While winter wheat lies dormant during a winter freeze, wheat normally requires between 110 and 130 days between planting and harvest, depending upon climate, seed type, and soil conditions. Crop management decisions require the knowledge of stage of development of the crop. In particular, spring fertilizer applications, herbicides, fungicides, growth regulators are typically applied at specific stages of plant development. For example, current recommendations often indicate the second application of nitrogen be done when the ear (not visible at this stage) is about 1 cm in size (Z31 on Zadoks scale). Knowledge of stages is also interesting to identify periods of higher risk, in terms of climate. For example, the meiosis stage is extremely susceptible to low temperatures (under 4 °C) or high temperatures (over 25 °C). Farmers also benefit from knowing when the flag leaf (last leaf) appears as this leaf represents about 75% of photosynthesis reactions during the grain filling period and as such should be preserved from disease or insect attacks to ensure a good yield. Several systems exist to identify crop stages, with the Feekes and Zadoks scales being the most widely used. Each scale is a standard system which describes successive stages reached by the crop during the agricultural season. - Wheat at the anthesis stage (face and side view) Estimates of the amount of wheat production lost owing to plant diseases vary between 10-25% in Missouri. A wide range of organisms infect wheat, of which the most important are viruses and fungi. Wheat is used as a food plant by the larvae of some Lepidoptera species including The Flame, Rustic Shoulder-knot, Setaceous Hebrew Character and Turnip Moth. # In the United States Classes used in the United States are - Durum — Very hard, translucent, light colored grain used to make semolina flour for pasta. - Hard Red Spring — Hard, brownish, high protein wheat used for bread and hard baked goods. Bread Flour and high gluten flours are commonly made from hard red spring wheat. It is primarily traded at the Minneapolis Grain Exchange. - Hard Red Winter — Hard, brownish, mellow high protein wheat used for bread, hard baked goods and as an adjunct in other flours to increase protein in pastry flour for pie crusts. Some brands of unbleached all-purpose flours are commonly made from hard red winter wheat alone. It is primarily traded by the Kansas City Board of Trade. - Soft Red Winter — Soft, low protein wheat used for cakes, pie crusts, biscuits, and muffins. Cake flour, pastry flour, and some self-rising flours with baking powder and salt added for example, are made from soft red winter wheat. It is primarily traded by the Chicago Board of Trade. - Hard White — Hard, light colored, opaque, chalky, medium protein wheat planted in dry, temperate areas. Used for bread and brewing. - Soft White — Soft, light colored, very low protein wheat grown in temperate moist areas. Used for pie crusts and pastry. Pastry flour, for example, is sometimes made from soft white winter wheat. Hard wheats are harder to process and red wheats may need bleaching. Therefore, soft and white wheats usually command higher prices than hard and red wheats on the commodities market. # As a food Raw wheat berries can be powdered into flour, germinated and dried creating malt, crushed and de-branned into cracked wheat, parboiled (or steamed), dried, crushed and de-branned into bulgur, or processed into semolina, pasta, or roux. They are a major ingredient in such foods as bread, breakfast cereals (e.g. Wheatena, Cream of Wheat), porridge, crackers, biscuits, pancakes, cakes, and gravy. # Nutrition 100 grams of hard red winter wheat contains about 12.6 grams of protein, 1.5 grams of total fat, 71 grams of carbohydrate (by difference), 12.2 grams of dietary fiber, and 3.2 mg of iron or 17% of the amount required daily. 100 grams of hard red spring wheat contains about 15.4 grams of protein, 1.9 grams of total fat, 68 grams of carbohydrate (by difference), 12.2 grams of dietary fiber, and 3.6 mg of iron or 20% of the amount required daily. Gluten protein found in wheat (and other Triticeae) is hard to digest, and intolerable for people with celiac disease (an autoimmune disorder in ~1% of Indo-European populations).	Wheat Wheat (Triticum spp.)[1] is a grass that is cultivated worldwide. Globally, it is an important human food grain ranking second in total production as a cereal crop behind maize; the third being rice.[2] Wheat grain is a staple food used to make flour for leavened, flat and steamed breads; cookies, cakes, pasta, noodles and couscous;[3] and for fermentation to make beer,[4] alcohol, vodka[5] or biofuel.[6] Wheat is planted to a limited extent as a forage crop for livestock, and the straw can be used as fodder for livestock or as a construction material for roofing thatch.[7][8] # History Wheat originated in Southwest Asia in the area known as the Fertile Crescent. The genetic relationships between einkorn and emmer indicate that the most likely site of domestication is near Diyarbakır in Turkey [9]. These wild wheats were domesticated as part of the origins of agriculture in the Fertile Crescent. Cultivation and repeated harvesting and sowing of the grains of wild grasses led to the domestication of wheat through selection of mutant forms with tough ears which remained intact during harvesting, larger grains, and a tendency for the spikelets to stay on the stalk until harvested [10]. Because of the loss of seed dispersal mechanisms, domesticated wheats have limited capacity to propagate in the wild.[11] The cultivation of wheat began to spread beyond the Fertile Crescent during the Neolithic period. By 5,000 years ago, wheat had reached Ethiopia, India, Ireland and Spain. A millennium later it reached China.[11] Three thousand years ago agricultural cultivation with horse drawn plows increased cereal grain production, as did the use of seed drills to replace broadcast sowing in the 18th century. Yields of wheat continued to increase, as new land came under cultivation and with improved agricultural husbandry involving the use of fertilizers, threshing machines and reaping machines (the 'combine harvester'), tractor-drawn cultivators and planters, and better varieties (see green revolution and Norin 10 wheat). With population growth rates falling, while yields continue to rise, the area devoted to wheat may now begin to decline for the first time in modern human history.[12] But now in 2007 wheat stocks have reached their lowest since 1981, and 2006 was the first year in which the world consumed more wheat than the world produced - a gap that is continuously widening as the requirement for wheat increases beyond production. The use of wheat as a bio-fuel will exacerbate the situation. # Genetics Wheat genetics is more complicated than that of most other domesticated species. Some wheat species are diploid, with two sets of chromosomes, but many are stable polyploids, with four sets of chromosomes (tetraploid) or six (hexaploid).[13] - Einkorn wheat (T. monococcum) is diploid.[1] - Most tetraploid wheats (e.g. emmer and durum wheat) are derived from wild emmer, T. dicoccoides. Wild emmer is the result of a hybridization between two diploid wild grasses, T. urartu and a wild goatgrass such as Aegilops searsii or Ae. speltoides. The hybridization that formed wild emmer occurred in the wild, long before domestication.[13] - Hexaploid wheats evolved in farmers' fields. Either domesticated emmer or durum wheat hybridized with yet another wild diploid grass (Aegilops tauschii) to make the hexaploid wheats, spelt wheat and bread wheat.[13] # Plant Breeding In traditional agricultural systems wheat is often grown as landraces, informal farmer-maintained populations that often maintain high levels of morophological diversity. Although landraces of wheat are no longer grown in Europe and North America, they continue to be important elsewhere. The origins of formal wheat breeding lie in the nineteenth century, when single line varieties were created through selection of seed from a single plant noted to have desired properties. Modern wheat breeding developed in the first years of the twentieth century and was closely linked to the development of Mendelian genetics. The standard method of breeding inbred wheat cultivars is by crossing two lines using hand emasculation, then selfing or inbreeding the progeny. Selections are identified (shown to have the genes responsible for the varietal differences) ten or more generations before release as a variety or cultivar.[14] F1 hybrid wheat cultivars should not be confused with wheat cultivars deriving from standard plant breeding. Heterosis or hybrid vigor (as in the familiar F1 hybrids of maize) occurs in common (hexaploid) wheat, but it is difficult to produce seed of hybrid cultivars on a commercial scale as is done with maize because wheat flowers are complete and normally self-pollinate.[14] Commercial hybrid wheat seed has been produced using chemical hybridizing agents, plant growth regulators that selectively interfere with pollen development, or naturally occurring cytoplasmic male sterility systems. Hybrid wheat has been a limited commercially success, in Europe (particularly France), the USA and South Africa.[15] # Hulled versus free-threshing wheat The four wild species of wheat, along with the domesticated varieties einkorn,[16] emmer[17] and spelt,[18] have hulls (in German, Spelzweizen). This more primitive morphology consists of toughened glumes that tightly enclose the grains, and (in domesticated wheats) a semi-brittle rachis that breaks easily on threshing. The result is that when threshed, the wheat ear breaks up into spikelets. To obtain the grain, further processing, such as milling or pounding, is needed to remove the hulls or husks. In contrast, in free-threshing (or naked) forms such as durum wheat and common wheat, the glumes are fragile and the rachis tough. On threshing, the chaff breaks up, releasing the grains. Hulled wheats are often stored as spikelets because the toughened glumes give good protection against pests of stored grain.[16] # Naming There are many botanical classification systems used for wheat species, discussed in a separate article on Wheat taxonomy. The name of a wheat species from one information source may not be the name of a wheat species in another. Within a species, wheat cultivars are further classified by wheat breeders and farmers in terms of growing season, such as winter wheat vs. spring wheat,[8] by gluten content, such as hard wheat (high protein content) vs. soft wheat (high starch content), or by grain color (red, white or amber). ## Major cultivated species of wheat - Common wheat or Bread wheat — (T. aestivum) A hexaploid species that is the most widely cultivated in the world. - Durum — (T. durum) The only tetraploid form of wheat widely used today, and the second most widely cultivated wheat. - Einkorn — (T. monococcum) A diploid species with wild and cultivated variants. Domesticated at the same time as emmer wheat, but never reached the same importance. - Emmer — (T. dicoccon) A tetraploid species, cultivated in ancient times but no longer in widespread use. - Spelt — (T. spelta) Another hexaploid species cultivated in limited quantities. # Economics Harvested wheat grain that enters trade is classified according to grain properties (see below) for the purposes of the commodities market. Wheat buyers use the classifications to help determine which wheat to purchase as each class has special uses. Wheat producers determine which classes of wheat are the most profitable to cultivate with this system. Wheat is widely cultivated as a cash crop because it produces a good yield per unit area, grows well in a temperate climate even with a moderately short growing season, and yields a versatile, high-quality flour that is widely used in baking. Most breads are made with wheat flour, including many breads named for the other grains they contain like most rye and oat breads. Many other popular foods are made from wheat flour as well, resulting in a large demand for the grain even in economies with a significant food surplus. In 2007 there was a dramatic rise in the price of wheat due to freezes and flooding in the northern hemisphere and a drought in Australia. Wheat futures in September, 2007 for December and March delivery had risen above $9.00 a bushel, prices never seen before.[19] There were complaints in Italy about the high price of pasta.[20] # Production and consumption statistics In 1997, global per capita wheat consumption was 101 kg, with the highest per capita consumption (623 kg) found in Denmark. See also International wheat production statistics. Unlike rice, wheat production is more widespread globally though China's share is almost one-sixth of the world. # Agronomy While winter wheat lies dormant during a winter freeze, wheat normally requires between 110 and 130 days between planting and harvest, depending upon climate, seed type, and soil conditions. Crop management decisions require the knowledge of stage of development of the crop. In particular, spring fertilizer applications, herbicides, fungicides, growth regulators are typically applied at specific stages of plant development. For example, current recommendations often indicate the second application of nitrogen be done when the ear (not visible at this stage) is about 1 cm in size (Z31 on Zadoks scale). Knowledge of stages is also interesting to identify periods of higher risk, in terms of climate. For example, the meiosis stage is extremely susceptible to low temperatures (under 4 °C) or high temperatures (over 25 °C). Farmers also benefit from knowing when the flag leaf (last leaf) appears as this leaf represents about 75% of photosynthesis reactions during the grain filling period and as such should be preserved from disease or insect attacks to ensure a good yield. Several systems exist to identify crop stages, with the Feekes and Zadoks scales being the most widely used. Each scale is a standard system which describes successive stages reached by the crop during the agricultural season. - Wheat at the anthesis stage (face and side view) Estimates of the amount of wheat production lost owing to plant diseases vary between 10-25% in Missouri.[22] A wide range of organisms infect wheat, of which the most important are viruses and fungi. Wheat is used as a food plant by the larvae of some Lepidoptera species including The Flame, Rustic Shoulder-knot, Setaceous Hebrew Character and Turnip Moth. # In the United States Classes used in the United States are - Durum — Very hard, translucent, light colored grain used to make semolina flour for pasta. - Hard Red Spring — Hard, brownish, high protein wheat used for bread and hard baked goods. Bread Flour and high gluten flours are commonly made from hard red spring wheat. It is primarily traded at the Minneapolis Grain Exchange. - Hard Red Winter — Hard, brownish, mellow high protein wheat used for bread, hard baked goods and as an adjunct in other flours to increase protein in pastry flour for pie crusts. Some brands of unbleached all-purpose flours are commonly made from hard red winter wheat alone. It is primarily traded by the Kansas City Board of Trade. - Soft Red Winter — Soft, low protein wheat used for cakes, pie crusts, biscuits, and muffins. Cake flour, pastry flour, and some self-rising flours with baking powder and salt added for example, are made from soft red winter wheat. It is primarily traded by the Chicago Board of Trade. - Hard White — Hard, light colored, opaque, chalky, medium protein wheat planted in dry, temperate areas. Used for bread and brewing. - Soft White — Soft, light colored, very low protein wheat grown in temperate moist areas. Used for pie crusts and pastry. Pastry flour, for example, is sometimes made from soft white winter wheat. Hard wheats are harder to process and red wheats may need bleaching. Therefore, soft and white wheats usually command higher prices than hard and red wheats on the commodities market. # As a food Raw wheat berries can be powdered into flour, germinated and dried creating malt, crushed and de-branned into cracked wheat, parboiled (or steamed), dried, crushed and de-branned into bulgur, or processed into semolina, pasta, or roux. They are a major ingredient in such foods as bread, breakfast cereals (e.g. Wheatena, Cream of Wheat), porridge, crackers, biscuits, pancakes, cakes, and gravy. # Nutrition 100 grams of hard red winter wheat contains about 12.6 grams of protein, 1.5 grams of total fat, 71 grams of carbohydrate (by difference), 12.2 grams of dietary fiber, and 3.2 mg of iron or 17% of the amount required daily. 100 grams of hard red spring wheat contains about 15.4 grams of protein, 1.9 grams of total fat, 68 grams of carbohydrate (by difference), 12.2 grams of dietary fiber, and 3.6 mg of iron or 20% of the amount required daily.[23] Gluten protein found in wheat (and other Triticeae) is hard to digest, and intolerable for people with celiac disease (an autoimmune disorder in ~1% of Indo-European populations).	https://www.wikidoc.org/index.php/Wheat
3e0056c2bcfca50126efb749273d5c8d9fcd8cf0	wikidoc	XB130	XB130 XB130 (also known as AFAP1L2) is a cytosolic adaptor protein and signal transduction mediator. XB130 regulates cell proliferation, cell survival, cell motility and gene expression. XB130 is highly similar to AFAP and is thus known as actin filament associated protein 1-like 2 (AFAP1L2). XB130 is a substrate and regulator of multiple tyrosine kinase-mediated signaling. XB130 is highly expressed in the thyroid and spleen. # Molecular structure The XB130 gene is located on human chromosome 10q25.3 and encodes an 818 amino acid protein. It has a molecular weight of approximately 130 kDa and is structurally similar to actin-filament-associated protein (AFAP) and is thus known as AFAP1L2. Several tyrosine phosphorylation sites and a proline rich sequence are included in the N-terminal region of XB130, which allows it to interact and activate c-Src-containing proteins, as well as bind to p85α of PI3K. Two pleckstrin-homology domains are located in the middle portion, giving XB130 its lipid-binding ability. The C-terminal region contains a coiled-coil domain, which shares partial similarity with AFAP's leucine zipper domain. Both the C-terminal and N-terminal regions of XB130 are required for XB130's role in its translocation to the lamellipodia. Despite XB130's structural similarity to AFAP, XB130 does not behave like an actin filament-associated protein. The actin-binding site present in AFAP is only partially present in XB130. # Function ## Role in cell cycle and survival XB130 has been demonstrated to play a role in cell proliferation and survival through the regulation of the PI3K/Akt signaling pathway. When tyrosine phosphorylated, XB130 has the ability to interact with the p85ɑ subunit of PI3K through its SH2 domains. This interaction leads to the subsequent activation of Akt, cell proliferation, and cell survival. Activated Akt promotes cell survival and cell cycle progression by phosphorylating and inactivating p21Cip1/WAF1, p27Kip1, and GSK3β, as well as inhibits apoptosis by preventing the cleavage of caspase-8 and caspase-9, which are involved in the extrinsic and intrinsic pathways of cell death, respectively.> Alternatively, when the expression of XB130 is suppressed in vitro, Akt phosphorylation and therefore activation becomes significantly reduced. This, in turn, leads to cell cycle arrest at G1/S phase and accelerated apoptosis. ## Role in cell motility and invasion During cytoskeletal rearrangement, a process required for cell motility, XB130 translocates to the cell periphery. XB130 exhibits a high affinity for peripheral F-actin structures, such as the lamellipodium. The translocation of XB130 to the cell periphery is particularly important in its potential to influence cell migration and metastasis. ## Role in gene expression The level of XB130 expression influences the expression of multiple genes related to cell proliferation and survival, and microRNAs miR-33a, 149a, and 193a-3p, all of which exhibit tumor suppressive function in thyroid cancer cells. ## Role in inflammation XB130 mediated c-Src binding and activation increases Interleukin-8 (IL-8), a chemokine produce by lung epithelial cells, which contains AP-1 and SRE transcription factor binding sites. These binding sites can be activated by the downregulation of XB130 expression and lead to a decrease in IL-8 production in lung cells. # Interactions XB130 (gene) has been known to interact with - SH2 domain of Src - SH3 domain of Src - c-Src - p85a subunit of PI3K - RET/PTC - GTPase-activating proteins (GAP) - Phospholipase C-gamma (PLC-γ) # Clinical significance Adaptor proteins play an important role as molecular scaffolds to mediate the transport and interaction of various proteins and is therefore highly involved in signal transduction. Deregulation of adaptor proteins is highly related to the abnormality of cellular functions and many adaptor proteins are frequently overexpressed in cancers. Clinical studies on the expression level and pattern of XB130 in various human tumors demonstrate that XB130 expression is regulated in thyroid and gastrointestinal cancer and soft tissue tumors. Expression level of XB130 was significantly higher in normal and benign lesion than that of papillary and anaplastic/insular carcinoma. Through the studies on many gastrointestinal cancers, the oncogenic roles of XB130 was shown. XB130 expression is significantly correlated with the survival time and disease-free period in gastric cancer patients. XB130 was identified as a potential colorectal cancer markers. XB130 protein level was elevated in human esophageal squamous carcinoma. In addition, XB130 was selected as one of six highly expressed genes related to local aggressiveness of soft tissue tumors in a set of 102 representative tumor samples. These findings suggest that XB130 may be involved in tumorigenesis and that XB130 is a potential diagnostic biomarker and therapeutic target for cancer. # Discovery This adaptor protein was discovered during molecular cloning of human actin filament associated protein (AFAP1) in the Latner Thoracic Surgery Research Laboratories Toronto, Ontario, Canada. The molecule is named XB130 after lead technician Xiaohui Bai and the molecular mass of the protein. This protein was found to have a high sequence identity to AFAP1, thus its name AFAP1L2.	XB130 XB130 (also known as AFAP1L2) is a cytosolic adaptor protein and signal transduction mediator. XB130 regulates cell proliferation, cell survival, cell motility and gene expression. XB130 is highly similar to AFAP and is thus known as actin filament associated protein 1-like 2 (AFAP1L2). XB130 is a substrate and regulator of multiple tyrosine kinase-mediated signaling. XB130 is highly expressed in the thyroid and spleen. # Molecular structure The XB130 gene is located on human chromosome 10q25.3 and encodes an 818 amino acid protein. It has a molecular weight of approximately 130 kDa and is structurally similar to actin-filament-associated protein (AFAP) and is thus known as AFAP1L2.[1] Several tyrosine phosphorylation sites and a proline rich sequence are included in the N-terminal region of XB130, which allows it to interact and activate c-Src-containing proteins, as well as bind to p85α of PI3K. Two pleckstrin-homology domains are located in the middle portion, giving XB130 its lipid-binding ability. The C-terminal region contains a coiled-coil domain, which shares partial similarity with AFAP's leucine zipper domain.[2] Both the C-terminal and N-terminal regions of XB130 are required for XB130's role in its translocation to the lamellipodia.[3] Despite XB130's structural similarity to AFAP, XB130 does not behave like an actin filament-associated protein. The actin-binding site present in AFAP is only partially present in XB130. # Function ## Role in cell cycle and survival XB130 has been demonstrated to play a role in cell proliferation and survival through the regulation of the PI3K/Akt signaling pathway. When tyrosine phosphorylated, XB130 has the ability to interact with the p85ɑ subunit of PI3K through its SH2 domains.[3] This interaction leads to the subsequent activation of Akt, cell proliferation, and cell survival. Activated Akt promotes cell survival and cell cycle progression by phosphorylating and inactivating p21Cip1/WAF1, p27Kip1, and GSK3β, as well as inhibits apoptosis by preventing the cleavage of caspase-8 and caspase-9, which are involved in the extrinsic and intrinsic pathways of cell death, respectively.[4]> Alternatively, when the expression of XB130 is suppressed in vitro, Akt phosphorylation and therefore activation becomes significantly reduced. This, in turn, leads to cell cycle arrest at G1/S phase and accelerated apoptosis.[5] ## Role in cell motility and invasion During cytoskeletal rearrangement, a process required for cell motility, XB130 translocates to the cell periphery. XB130 exhibits a high affinity for peripheral F-actin structures, such as the lamellipodium. The translocation of XB130 to the cell periphery is particularly important in its potential to influence cell migration and metastasis.[3] ## Role in gene expression The level of XB130 expression influences the expression of multiple genes related to cell proliferation and survival,[6] and microRNAs miR-33a, 149a, and 193a-3p, all of which exhibit tumor suppressive function in thyroid cancer cells.[7] ## Role in inflammation XB130 mediated c-Src binding and activation increases Interleukin-8 (IL-8), a chemokine produce by lung epithelial cells, which contains AP-1 and SRE transcription factor binding sites. These binding sites can be activated by the downregulation of XB130 expression and lead to a decrease in IL-8 production in lung cells.[1] # Interactions XB130 (gene) has been known to interact with - SH2 domain of Src - SH3 domain of Src - c-Src - p85a subunit of PI3K - RET/PTC - GTPase-activating proteins (GAP) - Phospholipase C-gamma (PLC-γ) # Clinical significance Adaptor proteins play an important role as molecular scaffolds to mediate the transport and interaction of various proteins and is therefore highly involved in signal transduction.[1] Deregulation of adaptor proteins is highly related to the abnormality of cellular functions and many adaptor proteins are frequently overexpressed in cancers. Clinical studies on the expression level and pattern of XB130 in various human tumors demonstrate that XB130 expression is regulated in thyroid [6] and gastrointestinal cancer[8][9][10] and soft tissue tumors.[11] Expression level of XB130 was significantly higher in normal and benign lesion than that of papillary and anaplastic/insular carcinoma.[6] Through the studies on many gastrointestinal cancers, the oncogenic roles of XB130 was shown. XB130 expression is significantly correlated with the survival time and disease-free period in gastric cancer patients.[8] XB130 was identified as a potential colorectal cancer markers.[9] XB130 protein level was elevated in human esophageal squamous carcinoma.[10] In addition, XB130 was selected as one of six highly expressed genes related to local aggressiveness of soft tissue tumors in a set of 102 representative tumor samples.[11] These findings suggest that XB130 may be involved in tumorigenesis and that XB130 is a potential diagnostic biomarker and therapeutic target for cancer. # Discovery This adaptor protein was discovered during molecular cloning of human actin filament associated protein (AFAP1) in the Latner Thoracic Surgery Research Laboratories Toronto, Ontario, Canada. The molecule is named XB130 after lead technician Xiaohui Bai and the molecular mass of the protein. This protein was found to have a high sequence identity to AFAP1, thus its name AFAP1L2.	https://www.wikidoc.org/index.php/XB130
c0074e51f6cab817fdb62615c2ae4a88f7bb0a6b	wikidoc	XRCC1	XRCC1 DNA repair protein XRCC1 also known as X-ray repair cross-complementing protein 1 is a protein that in humans is encoded by the XRCC1 gene. XRCC1 is involved in DNA repair where it complexes with DNA ligase III. # Function XRCC1 is involved in the efficient repair of DNA single-strand breaks formed by exposure to ionizing radiation and alkylating agents. This protein interacts with DNA ligase III, polymerase beta and poly (ADP-ribose) polymerase to participate in the base excision repair pathway. It may play a role in DNA processing during meiogenesis and recombination in germ cells. A rare microsatellite polymorphism in this gene is associated with cancer in patients of varying radiosensitivity. The XRCC1 protein does not have enzymatic activity, but acts as a scaffolding protein that interacts with multiple repair enzymes. The scaffolding allows these repair enzymes to then carry out their enzymatic steps in repairing DNA. XRCC1 is involved in single-strand break repair, base excision repair and nucleotide excision repair. As reviewed by London, XRCC1 protein has three globular domains connected by two linker segments of ~150 and 120 residues. The XRCC1 N-terminal domain binds to DNA polymerase beta, the C-terminal BRCT domain interacts with DNA ligase III alpha and the central domain contains a poly(ADP-ribose) binding motif. This central domain allows recruitment of XRCC1 to polymeric ADP-ribose that forms on PARP1 after PARP1 binds to single strand breaks. The first linker contains a nuclear localization sequence and also has a region that interacts with DNA repair protein REV1, and REV1 recruits translesion polymerases. The second linker interacts with polynucleotide kinase phosphatase ( PNKP) (that processes DNA broken ends during base excision repair), aprataxin (active in single-strand DNA repair and non-homologous end joining) and a third protein designated aprataxin- and PNKP-like factor. XRCC1 has an essential role in microhomology-mediated end joining (MMEJ) repair of double strand breaks. MMEJ is a highly error-prone DNA repair pathway that results in deletion mutations. XRCC1 is one of 6 proteins required for this pathway. # Over-expression in cancer XRCC1 is over-expressed in non-small-cell lung carcinoma (NSCLC), and at an even higher level in metastatic lymph nodes of NSCLC. # Under-expression in cancer Deficiency in XRCC1, due to being heterozygous for a mutated XRCC1 gene coding for a truncated XRCC1 protein, suppresses tumor growth in mice. Under three experimental conditions for inducing three types of cancer (colon cancer, melanoma or breast cancer), mice heterozygous for this XRCC1 mutation had substantially lower tumor volume or number than wild type mice undergoing the same carcinogenic treatments. # Comparison with other DNA repair genes in cancer Cancers are very often deficient in expression of one or more DNA repair genes, but over-expression of a DNA repair gene is less usual in cancer. For instance, at least 36 DNA repair proteins, when mutationally defective in germ line cells, cause increased risk of cancer (hereditary cancer syndromes). (Also see DNA repair-deficiency disorder.) Similarly, at least 12 DNA repair genes have frequently been found to be epigenetically repressed in one or more cancers. (See also Epigenetically reduced DNA repair and cancer.) Ordinarily, deficient expression of a DNA repair enzyme results in increased un-repaired DNA damages which, through replication errors (translesion synthesis), lead to mutations and cancer. However, XRCC1 mediated MMEJ repair is directly mutagenic, so in this case, over-expression, rather than under-expression, apparently leads to cancer. Reduction of mutagenic XRCC1 mediated MMEJ repair leads to reduced progression of cancer. # Structure The NMR solution structure of the Xrcc1 N-terminal domain (Xrcc1 NTD) shows that the structural core is a beta-sandwich with beta-strands connected by loops, three helices and two short two-stranded beta-sheets at each connection side. The Xrcc1 NTD specifically binds single-strand break DNA (gapped and nicked) and a gapped DNA-beta-Pol complex. # Interactions XRCC1 has been shown to interact with: - APEX1, - APTX, - OGG1, - PARP2, - PCNA, - PNKP, - POLB, and - PARP1.	XRCC1 DNA repair protein XRCC1 also known as X-ray repair cross-complementing protein 1 is a protein that in humans is encoded by the XRCC1 gene. XRCC1 is involved in DNA repair where it complexes with DNA ligase III. # Function XRCC1 is involved in the efficient repair of DNA single-strand breaks formed by exposure to ionizing radiation and alkylating agents. This protein interacts with DNA ligase III, polymerase beta and poly (ADP-ribose) polymerase to participate in the base excision repair pathway. It may play a role in DNA processing during meiogenesis and recombination in germ cells. A rare microsatellite polymorphism in this gene is associated with cancer in patients of varying radiosensitivity.[1] The XRCC1 protein does not have enzymatic activity, but acts as a scaffolding protein that interacts with multiple repair enzymes. The scaffolding allows these repair enzymes to then carry out their enzymatic steps in repairing DNA. XRCC1 is involved in single-strand break repair, base excision repair and nucleotide excision repair.[2] As reviewed by London,[2] XRCC1 protein has three globular domains connected by two linker segments of ~150 and 120 residues. The XRCC1 N-terminal domain binds to DNA polymerase beta, the C-terminal BRCT domain interacts with DNA ligase III alpha and the central domain contains a poly(ADP-ribose) binding motif. This central domain allows recruitment of XRCC1 to polymeric ADP-ribose that forms on PARP1 after PARP1 binds to single strand breaks. The first linker contains a nuclear localization sequence and also has a region that interacts with DNA repair protein REV1, and REV1 recruits translesion polymerases. The second linker interacts with polynucleotide kinase phosphatase ( PNKP) (that processes DNA broken ends during base excision repair), aprataxin (active in single-strand DNA repair and non-homologous end joining) and a third protein designated aprataxin- and PNKP-like factor. XRCC1 has an essential role in microhomology-mediated end joining (MMEJ) repair of double strand breaks. MMEJ is a highly error-prone DNA repair pathway that results in deletion mutations. XRCC1 is one of 6 proteins required for this pathway.[3] # Over-expression in cancer XRCC1 is over-expressed in non-small-cell lung carcinoma (NSCLC),[4] and at an even higher level in metastatic lymph nodes of NSCLC.[5] # Under-expression in cancer Deficiency in XRCC1, due to being heterozygous for a mutated XRCC1 gene coding for a truncated XRCC1 protein, suppresses tumor growth in mice.[6] Under three experimental conditions for inducing three types of cancer (colon cancer, melanoma or breast cancer), mice heterozygous for this XRCC1 mutation had substantially lower tumor volume or number than wild type mice undergoing the same carcinogenic treatments. # Comparison with other DNA repair genes in cancer Cancers are very often deficient in expression of one or more DNA repair genes, but over-expression of a DNA repair gene is less usual in cancer. For instance, at least 36 DNA repair proteins, when mutationally defective in germ line cells, cause increased risk of cancer (hereditary cancer syndromes).[7] (Also see DNA repair-deficiency disorder.) Similarly, at least 12 DNA repair genes have frequently been found to be epigenetically repressed in one or more cancers.[7] (See also Epigenetically reduced DNA repair and cancer.) Ordinarily, deficient expression of a DNA repair enzyme results in increased un-repaired DNA damages which, through replication errors (translesion synthesis), lead to mutations and cancer. However, XRCC1 mediated MMEJ repair is directly mutagenic, so in this case, over-expression, rather than under-expression, apparently leads to cancer. Reduction of mutagenic XRCC1 mediated MMEJ repair leads to reduced progression of cancer. # Structure The NMR solution structure of the Xrcc1 N-terminal domain (Xrcc1 NTD) shows that the structural core is a beta-sandwich with beta-strands connected by loops, three helices and two short two-stranded beta-sheets at each connection side. The Xrcc1 NTD specifically binds single-strand break DNA (gapped and nicked) and a gapped DNA-beta-Pol complex.[8] # Interactions XRCC1 has been shown to interact with: - APEX1,[9] - APTX,[10][11] - OGG1,[12] - PARP2,[13] - PCNA,[14] - PNKP,[15][16] - POLB,[14][17][18][19] and - PARP1.[11][20]	https://www.wikidoc.org/index.php/XRCC1
45fc1fe6a448c39bad5362564cce33ada51c237f	wikidoc	XRCC2	XRCC2 DNA repair protein XRCC2 is a protein that in humans is encoded by the XRCC2 gene. # Function This gene encodes a member of the RecA/Rad51-related protein family that participates in homologous recombination to maintain chromosome stability and repair DNA damage. This gene is involved in the repair of DNA double-strand breaks by homologous recombination and it functionally complements Chinese hamster irs1, a repair-deficient mutant that exhibits hypersensitivity to a number of different DNA-damaging agents. The XRCC2 protein is one of five human paralogs of RAD51, including RAD51B (RAD51L1), RAD51C (RAD51L2), RAD51D (RAD51L3), XRCC2 and XRCC3. They each share about 25% amino acid sequence identity with RAD51 and each other. The RAD51 paralogs are all required for efficient DNA double-strand break repair by homologous recombination and depletion of any paralog results in significant decreases in homologous recombination frequency. XRCC2 forms a four-part complex with three related paralogs: BCDX2 (RAD51B-RAD51C-RAD51D-XRCC2) while two paralogs form a second complex CX3 (RAD51C-XRCC3). These two complexes act at two different stages of homologous recombinational DNA repair. The BCDX2 complex is responsible for RAD51 recruitment or stabilization at damage sites. The BCDX2 complex appears to act by facilitating the assembly or stability of the RAD51 nucleoprotein filament. The CX3 complex acts downstream of RAD51 recruitment to damage sites. The CX3 complex was shown to associate with Holliday junction resolvase activity, probably in a role of stabilizing gene conversion tracts. # Interactions XRCC2 has been shown to interact with RAD51L3, Bloom syndrome protein and RAD51C. # Epigenetic deficiency in cancer There are two known epigenetic causes of XRCC2 deficiency that appear to increase cancer risk. These are methylation of the XRCC2 promoter and epigenetic repression of XRCC2 by over-expression of EZH2 protein. The XRCC2 gene was found to be hypermethylated in the promoter region in 52 of 54 cases of cervical cancer. Promoter hypermethylation reduces gene expression, and thus would reduce the tumor suppressing homologous recombinational repair otherwise supported by XRCC2. Increased expression of EZH2 leads to epigenetic repression of RAD51 paralogs, including XRCC2, and thus reduces homologous recombinational repair. This reduction was proposed to be a cause of breast cancer. EZH2 is the catalytic subunit of Polycomb Repressor Complex 2 (PRC2) which catalyzes methylation of histone H3 at lysine 27 (H3K27me) and mediates gene silencing of target genes via local chromatin reorganization. EZH2 protein is up-regulated in numerous cancers. EZH2 mRNA is up-regulated, on average, 7.5-fold in breast cancer, and between 40% to 75% of breast cancers have over-expressed EZH2 protein.	XRCC2 DNA repair protein XRCC2 is a protein that in humans is encoded by the XRCC2 gene.[1][2][3] # Function This gene encodes a member of the RecA/Rad51-related protein family that participates in homologous recombination to maintain chromosome stability and repair DNA damage. This gene is involved in the repair of DNA double-strand breaks by homologous recombination and it functionally complements Chinese hamster irs1, a repair-deficient mutant that exhibits hypersensitivity to a number of different DNA-damaging agents.[3] The XRCC2 protein is one of five human paralogs of RAD51, including RAD51B (RAD51L1), RAD51C (RAD51L2), RAD51D (RAD51L3), XRCC2 and XRCC3. They each share about 25% amino acid sequence identity with RAD51 and each other.[4] The RAD51 paralogs are all required for efficient DNA double-strand break repair by homologous recombination and depletion of any paralog results in significant decreases in homologous recombination frequency.[5] XRCC2 forms a four-part complex with three related paralogs: BCDX2 (RAD51B-RAD51C-RAD51D-XRCC2) while two paralogs form a second complex CX3 (RAD51C-XRCC3). These two complexes act at two different stages of homologous recombinational DNA repair. The BCDX2 complex is responsible for RAD51 recruitment or stabilization at damage sites.[5] The BCDX2 complex appears to act by facilitating the assembly or stability of the RAD51 nucleoprotein filament. The CX3 complex acts downstream of RAD51 recruitment to damage sites.[5] The CX3 complex was shown to associate with Holliday junction resolvase activity, probably in a role of stabilizing gene conversion tracts.[5] # Interactions XRCC2 has been shown to interact with RAD51L3,[6][7][8][9] Bloom syndrome protein[7] and RAD51C.[9][10] # Epigenetic deficiency in cancer There are two known epigenetic causes of XRCC2 deficiency that appear to increase cancer risk. These are methylation of the XRCC2 promoter and epigenetic repression of XRCC2 by over-expression of EZH2 protein. The XRCC2 gene was found to be hypermethylated in the promoter region in 52 of 54 cases of cervical cancer.[11] Promoter hypermethylation reduces gene expression, and thus would reduce the tumor suppressing homologous recombinational repair otherwise supported by XRCC2. Increased expression of EZH2 leads to epigenetic repression of RAD51 paralogs, including XRCC2, and thus reduces homologous recombinational repair.[12] This reduction was proposed to be a cause of breast cancer.[12] EZH2 is the catalytic subunit of Polycomb Repressor Complex 2 (PRC2) which catalyzes methylation of histone H3 at lysine 27 (H3K27me) and mediates gene silencing of target genes via local chromatin reorganization.[13] EZH2 protein is up-regulated in numerous cancers.[13][14] EZH2 mRNA is up-regulated, on average, 7.5-fold in breast cancer, and between 40% to 75% of breast cancers have over-expressed EZH2 protein.[15]	https://www.wikidoc.org/index.php/XRCC2
b288df81518245b0c7ca320161d8af98cc83a390	wikidoc	XRCC3	XRCC3 DNA repair protein XRCC3 is a protein that in humans is encoded by the XRCC3 gene. # Function This gene encodes a member of the RecA/Rad51-related protein family that participates in homologous recombination to maintain chromosome stability and repair DNA damage. This gene functionally complements Chinese hamster irs1SF, a repair-deficient mutant that exhibits hypersensitivity to a number of different DNA-damaging agents and is chromosomally unstable. A rare microsatellite polymorphism in this gene is associated with cancer in patients of varying radiosensitivity. The XRCC3 protein is one of five paralogs of RAD51, including RAD51B (RAD51L1), RAD51C (RAD51L2), RAD51D (RAD51L3), XRCC2 and XRCC3. They each share about 25% amino acid sequence identity with RAD51 and each other. The RAD51 paralogs are all required for efficient DNA double-strand break repair by homologous recombination and depletion of any paralog results in significant decreases in homologous recombination frequency. Two paralogs form a complex designated CX3 (RAD51C-XRCC3). Four paralogs form a second complex designated BCDX2 (RAD51B-RAD51C-RAD51D-XRCC2). These two complexes act at two different stages of homologous recombinational DNA repair. The CX3 complex acts downstream of RAD51, after its recruitment to damage sites. The CX3 complex associates with Holliday junction resolvase activity, probably in a role of stabilizing gene conversion tracts. The BCDX2 complex is responsible for RAD51 recruitment or stabilization at damage sites. The BCDX2 complex appears to act by facilitating the assembly or stability of the RAD51 nucleoprotein filament. # Interactions XRCC3 has been shown to interact with RAD51C. # Epigenetic deficiency in cancer There is an epigenetic cause of XRCC3 deficiency that appears to increase cancer risk. This is the repression of XRCC3 by over-expression of EZH2 protein. Increased expression of EZH2 leads to epigenetic repression of RAD51 paralogs, including XRCC3, and thus reduces homologous recombinational repair. This reduction was proposed to be a cause of breast cancer. EZH2 is the catalytic subunit of Polycomb Repressor Complex 2 (PRC2) which catalyzes methylation of histone H3 at lysine 27 (H3K27me) and mediates gene silencing of target genes via local chromatin reorganization. EZH2 protein is up-regulated in numerous cancers. EZH2 mRNA is up-regulated, on average, 7.5-fold in breast cancer, and between 40% to 75% of breast cancers have over-expressed EZH2 protein. # Interactive pathway map Click on genes, proteins and metabolites below to link to respective articles. - ↑ The interactive pathway map can be edited at WikiPathways: "FluoropyrimidineActivity_WP1601"..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}	XRCC3 DNA repair protein XRCC3 is a protein that in humans is encoded by the XRCC3 gene.[1] # Function This gene encodes a member of the RecA/Rad51-related protein family that participates in homologous recombination to maintain chromosome stability and repair DNA damage. This gene functionally complements Chinese hamster irs1SF, a repair-deficient mutant that exhibits hypersensitivity to a number of different DNA-damaging agents and is chromosomally unstable. A rare microsatellite polymorphism in this gene is associated with cancer in patients of varying radiosensitivity.[2] The XRCC3 protein is one of five paralogs of RAD51, including RAD51B (RAD51L1), RAD51C (RAD51L2), RAD51D (RAD51L3), XRCC2 and XRCC3. They each share about 25% amino acid sequence identity with RAD51 and each other.[3] The RAD51 paralogs are all required for efficient DNA double-strand break repair by homologous recombination and depletion of any paralog results in significant decreases in homologous recombination frequency.[4] Two paralogs form a complex designated CX3 (RAD51C-XRCC3). Four paralogs form a second complex designated BCDX2 (RAD51B-RAD51C-RAD51D-XRCC2). These two complexes act at two different stages of homologous recombinational DNA repair. The CX3 complex acts downstream of RAD51, after its recruitment to damage sites.[4] The CX3 complex associates with Holliday junction resolvase activity, probably in a role of stabilizing gene conversion tracts.[4] The BCDX2 complex is responsible for RAD51 recruitment or stabilization at damage sites.[4] The BCDX2 complex appears to act by facilitating the assembly or stability of the RAD51 nucleoprotein filament. # Interactions XRCC3 has been shown to interact with RAD51C.[5][6][7][8] # Epigenetic deficiency in cancer There is an epigenetic cause of XRCC3 deficiency that appears to increase cancer risk. This is the repression of XRCC3 by over-expression of EZH2 protein. Increased expression of EZH2 leads to epigenetic repression of RAD51 paralogs, including XRCC3, and thus reduces homologous recombinational repair.[9] This reduction was proposed to be a cause of breast cancer.[9] EZH2 is the catalytic subunit of Polycomb Repressor Complex 2 (PRC2) which catalyzes methylation of histone H3 at lysine 27 (H3K27me) and mediates gene silencing of target genes via local chromatin reorganization.[10] EZH2 protein is up-regulated in numerous cancers.[10][11] EZH2 mRNA is up-regulated, on average, 7.5-fold in breast cancer, and between 40% to 75% of breast cancers have over-expressed EZH2 protein.[12] # Interactive pathway map Click on genes, proteins and metabolites below to link to respective articles.[§ 1] - ↑ The interactive pathway map can be edited at WikiPathways: "FluoropyrimidineActivity_WP1601"..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/XRCC3
4ef1b8c68f19ff15cf6415c199f600446fce17da	wikidoc	XYLT2	XYLT2 Xylosyltransferase 2 is an enzyme that in humans is encoded by the XYLT2 gene. # Function The protein encoded by this gene is an isoform of xylosyltransferase, which belongs to a family of glycosyltransferases. This enzyme transfers xylose from UDP-xylose to specific serine residues of the core protein and initiates the biosynthesis of glycosaminoglycan chains in proteoglycans including chondroitin sulfate, heparan sulfate, heparin and dermatan sulfate. # Clinical significance The enzyme activity, which is increased in scleroderma patients, is a diagnostic marker for the determination of sclerotic activity in systemic sclerosis. Mutations in this gene have been shown to be the cause of the spondylo-ocular syndrome. It has also been implicated as cofactor in pseudoxanthoma elasticum.	XYLT2 Xylosyltransferase 2 is an enzyme that in humans is encoded by the XYLT2 gene.[1][2] # Function The protein encoded by this gene is an isoform of xylosyltransferase, which belongs to a family of glycosyltransferases. This enzyme transfers xylose from UDP-xylose to specific serine residues of the core protein and initiates the biosynthesis of glycosaminoglycan chains in proteoglycans including chondroitin sulfate, heparan sulfate, heparin and dermatan sulfate.[2] # Clinical significance The enzyme activity, which is increased in scleroderma patients, is a diagnostic marker for the determination of sclerotic activity in systemic sclerosis.[2] Mutations in this gene have been shown to be the cause of the spondylo-ocular syndrome.[3] It has also been implicated as cofactor in pseudoxanthoma elasticum.	https://www.wikidoc.org/index.php/XYLT2
36ae44639352f03307ab8b9796c7a74d268a78a8	wikidoc	Xenin	Xenin Xenin is a peptide hormone produced by a subpopulation of chromogranin A-positive endocrine cells in the mucous membrane of the duodenum. The peptide has been found in humans, dogs, pigs, rats, and rabbits. In humans, xenin circulates in the blood plasma. There is a relationship between peaks of xenin concentration in the plasma and the third phase of the Migrating Motor Complex. For example, infusion of synthetic xenin in fasting volunteers will cause phase III activity. After a meal (the 'postprandial state'), infusion of xenin increases both frequency and the percentage of aborally propagated contractions. In higher concentrations xenin stimulates exocrine pancreatic secretion and inhibits the gastrin-stimulated secretion of acid in dogs. Xenin is also produced in neuroendocrine tumors of the duodenal mucosa. In vitro, xenin interacts with the neurotensin receptor 1. # Structure and sequence Xenin is a 25-amino acid polypeptide. The amino acid sequence of xenin is identical to the N-terminal end of cytoplasmic coatomer subunit alpha, from which xenin can be cleaved by aspartic proteases. Xenin is structurally related to the amphibian peptide xenopsin and to the neuropeptide neurotensin. # Proxenin Proxenin is the precursor to xenin. It is a 35-amino acid polypeptide. Like xenin, its amino acid sequence exactly matches the N-terminus of coatomer subunit alpha. # As a drug target Xenin promotes beta-cell survival and xenin has been evaluated in animal models of obesity and diabetes where it has demonstrated an antidiabetic potential. In humans, co-administration of xenin-25 and gastric inhibitory polypeptide (GIP) reduces postprandial glycemia by delaying gastric emptying.	Xenin Xenin is a peptide hormone produced by a subpopulation of chromogranin A-positive endocrine cells in the mucous membrane of the duodenum. The peptide has been found in humans, dogs, pigs, rats, and rabbits. In humans, xenin circulates in the blood plasma.[1] There is a relationship between peaks of xenin concentration in the plasma and the third phase of the Migrating Motor Complex. For example, infusion of synthetic xenin in fasting volunteers will cause phase III activity. After a meal (the 'postprandial state'), infusion of xenin increases both frequency and the percentage of aborally propagated contractions. In higher concentrations xenin stimulates exocrine pancreatic secretion and inhibits the gastrin-stimulated secretion of acid in dogs. Xenin is also produced in neuroendocrine tumors of the duodenal mucosa. In vitro, xenin interacts with the neurotensin receptor 1. # Structure and sequence Xenin is a 25-amino acid polypeptide. The amino acid sequence of xenin is identical to the N-terminal end of cytoplasmic coatomer subunit alpha,[2] from which xenin can be cleaved by aspartic proteases. Xenin is structurally related to the amphibian peptide xenopsin and to the neuropeptide neurotensin. # Proxenin Proxenin is the precursor to xenin. It is a 35-amino acid polypeptide. Like xenin, its amino acid sequence exactly matches the N-terminus of coatomer subunit alpha.[2] # As a drug target Xenin promotes beta-cell survival and xenin has been evaluated in animal models of obesity and diabetes where it has demonstrated an antidiabetic potential.[3] In humans, co-administration of xenin-25 and gastric inhibitory polypeptide (GIP) reduces postprandial glycemia by delaying gastric emptying. [4]	https://www.wikidoc.org/index.php/Xenin
498c1befe2d44b4ee3f4f5171c3de6846cb51660	wikidoc	Xenon	Xenon # Overview Xenon (Template:PronEng in the UK, Template:IPA in the US) is a chemical element that has the symbol Xe and atomic number 54. A colorless, heavy, odorless noble gas, xenon occurs in the earth's atmosphere in trace amounts. Although generally unreactive, xenon can undergo a few chemical reactions such as the formation of xenon hexafluoroplatinate, the first noble gas compound to be synthesized. Naturally occurring xenon is made of nine stable isotopes, but there are also over 40 unstable isotopes that undergo radioactive decay. The isotope ratios of xenon are an important tool for studying the early history of the Solar System. Xenon-135 is produced as a result of nuclear fission and acts as a neutron absorber in nuclear reactors. Xenon is used in flash lamps and arc lamps, and as a general anesthetic. The first excimer laser design used a xenon dimer molecule (Xe2) as its lasing medium, and the earliest laser designs used xenon flash lamps as pumps. Xenon is also being used to search for hypothetical weakly interactive massive particles and as the propellant for ion thrusters in spacecraft. # History Xenon was discovered in England by William Ramsay and Morris Travers on July 12, 1898, shortly after their discovery of the elements krypton and neon. They found it in the residue left over from evaporating components of liquid air. Ramsay suggested the name xenon for this gas from the Greek word ξένον , neuter singular form of ξένος , meaning foreign, strange, or host. In 1902, Ramsay estimated the proportion of xenon in the Earth's atmosphere as one part in 20 million. During the 1930s, the engineer Harold Edgerton began exploring strobe light technology for high-speed photography. This led him to the invention of the xenon flash lamp, in which light is generated by sending a brief electrical current through a tube filled with xenon gas. In 1934, Edgerton was able to generate flashes as brief as one microsecond with this method. Albert R. Behnke Jr. began exploring the causes of "drunkenness" in deep-sea divers in 1939. He tested the effects of varying the breathing mixtures on his subjects, and discovered that this caused the divers to perceive a change in depth. From his results, he deduced that xenon gas could serve as an anesthetic. Although Lazharev, in Russia, apparently studied xenon anesthesia in 1941, the first published report confirming xenon anesthesia was in 1946 by J. H. Lawrence, who experimented on mice. Xenon was first used as a surgical anesthetic in 1951 by Stuart C. Cullen, who successfully operated on two patients. In 1960, the physicist John H. Reynolds discovered that certain meteorites contained an isotopic anomaly in the form of an overabundance of xenon-129. He inferred that this was a decay product of radioactive iodine-129. As the half-life of 129I is 16 million years, this demonstrated that the meteorites were formed during the early history of the Solar System, as the 129I isotope was likely generated before the Solar System was formed. Xenon and the other noble gases were for a long time considered to be completely chemically inert and not able to form compounds. However, while teaching at the University of British Columbia, Neil Bartlett discovered that the gas platinum hexafluoride (PtF6) was a powerful oxidizing agent that could oxidize oxygen (O2) to form dioxygenyl hexafluoroplatinate (O2+−). Since O2 and xenon have almost the same first ionization potential, Bartlett realized that platinum hexafluoride might also be able to oxidize xenon. On March 23, 1962, he mixed the two gases and produced the first known compound of a noble gas, xenon hexafluoroplatinate. Bartlett thought its composition to be Xe+−, although later work has revealed that it was probably a mixture of various xenon-containing salts. Since then, many other xenon compounds have been discovered, and some compounds of the noble gases argon, krypton, and radon have been identified, including argon fluorohydride (HArF), krypton difluoride (KrF2), and radon fluoride. # Occurrence Xenon is a trace gas in Earth's atmosphere, occurring at 0.087±0.001 parts per million (μL/L). It is also found in gases emitted from some mineral springs. Some radioactive species of xenon, for example, 133Xe and 135Xe, are produced by neutron irradiation of fissionable material within nuclear reactors. Xenon is obtained commercially as a byproduct of the separation of air into oxygen and nitrogen. After this separation, generally performed by fractional distillation in a double-column plant, the liquid oxygen produced will contain small quantities of krypton and xenon. By additional fractional distillation steps, the liquid oxygen may be enriched to contain 0.1–0.2% of a krypton/xenon mixture, which is extracted either via adsorption onto silica gel or by distillation. Finally, the krypton/xenon mixture may be separated into krypton and xenon via distillation. Extraction of a liter of xenon from the atmosphere requires 220 watt-hours -f energy. Worldwide production of xenon in 1998 was estimated at 5,000–7,000 m3. Due to its low abundance, xenon is much more expensive than the lighter noble gases—approximate prices for the purchase of small quantities in Europe in 1999 were 10 €/L for xenon, 1 €/L for krypton, and 0.20 €/L for neon. Xenon is relatively rare in the Sun's atmosphere, on Earth, and in the asteroids and comets. The atmosphere of Mars shows a similar xenon abundance to that of Earth: 0.08 parts per million. However, Mars shows a higher proportion of 129Xe than the Earth or the Sun. As this isotope is generated by radioactive decay, the result may indicate that Mars lost most of its primordial atmosphere, possibly within the first 100 million years after the planet was formed. By contrast, the planet Jupiter has an unusually high abundance of xenon in its atmosphere; about 2.6 times as much as the Sun. This high abundance remains unexplained, but may have been caused by an early and rapid buildup of planetesimals—small, subplanetary bodies—before the presolar disk began to heat up. (Otherwise, xenon would not have been trapped in the planetesimal ices.) Within the Solar System, the nucleon fraction for all isotopes of xenon is 1.56 × 10-8, or one part in 64 million of the total mass. The problem of the low terrestrial xenon may potentially be explained by covalent bonding of xenon to oxygen within quartz, hence reducing the outgassing of xenon into the atmosphere. Unlike the lower mass noble gases, the normal stellar nucleosynthesis process inside a star does not form xenon. Elements more massive than iron-56 have a net energy cost to produce through fusion, so there is no energy gain for a star to create xenon. Instead, many isotopes of xenon are formed during supernova explosions. # Characteristics An atom of xenon is defined as having a nucleus with 54 protons. At standard temperature and pressure, pure xenon gas has a density of 5.761 kg/m3, about 4.5 times the surface density of the Earth's atmosphere, 1.217 kg/m3. As a liquid, xenon has a density of up to 3.100 g/mL, with the density maximum occurring at the triple point. Under the same conditions, the density of solid xenon, 3.640 g/cm3, is larger than the average density of granite, 2.75 g/cm3. Using gigapascals of pressure, xenon has been forced into a metallic phase. Xenon is a member of the zero-valence elements that are called noble or inert gases. It is inert to most common chemical reactions (such as combustion, for example) because the outer valence shell is completely filled with eight electrons. This produces a stable, minimum energy configuration in which the outer electrons are tightly bound. However, xenon can be oxidized by powerful oxidizing agents, and many xenon compounds have been synthesized. In a gas-filled tube, xenon emits a blue or lavenderish glow when the gas is excited by electrical discharge. Xenon emits a band of emission lines that span the visual spectrum, but the most intense lines occur in the region of blue light, which produces the coloration. # Isotopes Naturally occurring xenon is made of nine stable isotopes. The isotopes 124Xe, 134Xe and 136Xe are predicted to undergo double beta decay, but this has never been observed so they are considered to be stable. Besides these stable forms, there are over 40 unstable isotopes that have been studied. 129Xe is produced by beta decay of 129I, which has a half-life of 16 million years, while 131mXe, 133Xe, 133mXe, and 135Xe are some of the fission products of both 235U and 239Pu, and therefore used as indicators of nuclear explosions. The various isotopes of xenon are produced from supernova explosions, red giant stars that have exhausted the hydrogen at their cores and entered the asymptotic giant branch, classical novae explosions and the radioactive decay of elements such as iodine, uranium and plutonium. The artificial isotope 135Xe is of considerable significance in the operation of nuclear fission reactors. 135Xe has a huge cross section for thermal neutrons, 2.6×106 barns, so it acts as a neutron absorber or "poison" that can slow or stop the chain reaction after a period of operation. This was discovered in the earliest nuclear reactors built by the American Manhattan Project for plutonium production. Fortunately the designers had made provisions in the design to increase the reactor's reactivity (the number of neutrons per fission that go on to fission other atoms of nuclear fuel). Under adverse conditions, relatively high concentrations of radioactive xenon isotopes may be found emanating from nuclear reactors due to the release of fission products from cracked fuel rods, or fissioning of uranium in cooling water. Because xenon is a tracer for two parent isotopes, xenon isotope ratios in meteorites are a powerful tool for studying the formation of the solar system. The iodine-xenon method of dating gives the time elapsed between nucleosynthesis and the condensation of a solid object from the solar nebula. Xenon isotopic ratios such as 129Xe/130Xe and 136Xe/130Xe are also a powerful tool for understanding terrestrial differentiation and early outgassing. Excess 129Xe found in carbon dioxide well gases from New Mexico was believed to be from the decay of mantle-derived gases soon after Earth's formation. # Compounds Xenon hexafluoroplatinate was the first chemical compound of xenon, synthesized in 1962. Following this, many additional compounds of xenon have been discovered. These include xenon difluoride (XeF2), xenon tetrafluoride (XeF4), xenon hexafluoride (XeF6), xenon tetroxide (XeO4), and sodium perxenate (Na4XeO6). A highly explosive compound, xenon trioxide (XeO3), has also been made. Most of the more than 80 xenon compounds found to date contain electro-negative fluorine or oxygen. When other atoms are bound (such as hydrogen or carbon), they are often part of a molecule containing fluorine or oxygen. Some compounds of xenon are colored but most are colorless. In 1995, a group of scientists at the University of Helsinki in Finland (M. Räsänen and co-workers) announced the preparation of xenon dihydride (HXeH), and later xenon hydride-hydroxide (HXeOH), hydroxenoacetylene (HXeCCH), and other Xe-containing molecules. Deuterated molecules, HXeOD and DXeOH, have also been produced. As well as compounds where xenon forms a chemical bond, xenon can form clathrates—substances where xenon atoms are trapped by the crystalline lattice of another compound. An example is xenon hydrate (Xe·5.75 H2O), where xenon atoms occupy vacancies in a lattice of water molecules. The deuterated version of this hydrate has also been produced. Such clathrate hydrates can occur naturally under conditions of high pressure, such as in Lake Vostok underneath the Antarctic ice sheet. Clathrate formation can be used to fractionally distill xenon, argon and krypton. Xenon can also form endohedral fullerene compounds, where a xenon atom is trapped inside a fullerene molecule. The xenon atom trapped in the fullerene can be monitored via 129Xe nuclear magnetic resonance spectroscopy. Using this technique, chemical reactions on the fullerene molecule can be analyzed, due to the sensitivity of the chemical shift of the xenon atom to its environment. However, the xenon atom also has an electronic influence on the reactivity of the fullerene. # Applications Although xenon is rare and relatively expensive to extract from the Earth's atmosphere, it still has a number of applications. ## Illumination and optics ### Gas-discharge lamps Xenon is used in light-emitting devices called xenon flash lamps, which are used in photographic flashes and stroboscopic lamps; to excite the active medium in lasers which then generate coherent light; and, occasionally, in bactericidal lamps. The first solid-state laser, invented in 1960, was pumped by a xenon flash lamp, and lasers used to power inertial confinement fusion are also pumped by xenon flash lamps. Continuous, short-arc, high pressure xenon arc lamps have a color temperature closely approximating noon sunlight and are used in solar simulators. That is, the chromaticity of these lamps closely approximates a heated black-body radiator that has a temperature close to that observed from the Sun. After they were first introduced during the 1940s, these lamps began replacing the shorter-lived carbon arc lamps in movie projectors. They are employed in typical 35mm and IMAX film projection systems, automotive HID headlights and other specialized uses. These arc lamps are an excellent source of short wavelength ultraviolet radiation and they have intense emissions in the near infrared, which is used in some night vision systems. The individual cells in a plasma display use a mixture of xenon and neon that is converted into a plasma using electrodes. The interaction of this plasma with the electrodes generates ultraviolet photons, which then excite the phosphor coating on the front of the display. Xenon is used as a "starter gas" in high pressure sodium lamps. It has the lowest thermal conductivity and lowest ionization potential of all the non-radioactive noble gases. As a noble gas, it does not interfere with the chemical reactions occurring in the operating lamp. The low thermal conductivity minimizes thermal losses in the lamp while in the operating state, and the low ionization potential causes the breakdown voltage of the gas to be relatively low in the cold state, which allows the lamp to be more easily started. ### Lasers In 1962, a group of researchers at Bell Laboratories discovered laser action in xenon, and later found that the laser gain was improved by adding helium to the lasing medium. The first excimer laser used a xenon dimer (Xe2) energized by a beam of electrons to produce stimulated emission at an ultraviolet wavelength of 176 nm. Xenon chloride and xenon fluoride have also been used in excimer (or, more accurately, exciplex) lasers. The xenon chloride excimer laser has been employed, for example, in certain dermatological uses. ## Anesthesia Xenon has been used as a general anesthetic, although it is expensive. Even so, anesthesia machines that can deliver xenon are about to appear on the European market. Two mechanisms for xenon anesthesia have been proposed. The first one involves the inhibition of the calcium ATPase pump—the mechanism cells use to remove calcium (Ca2+)—in the cell membrane of synapses. This results from a conformational change when xenon binds to nonpolar sites inside the protein. The second mechanism focuses on the non-specific interactions between the anesthetic and the lipid membrane. Xenon has a minimum alveolar concentration (MAC) of 0.63, making it 50% more potent than N2O as an anesthetic. Thus it can be used in concentrations with oxygen that have a lower risk of hypoxia. Unlike nitrous oxide (N2O), xenon is not a greenhouse gas and so it is also viewed as environmentally friendly. Because of the high cost of xenon, however, economic application will require a closed system so that the gas can be recycled, with the gas being appropriately filtered for contaminants between uses. ## Medical imaging Gamma emission from the radioisotope 133Xe of xenon can be used to image the heart, lungs, and brain, for example, by means of single photon emission computed tomography. 133Xe has also been used to measure blood flow. Nuclei of only two of the stable isotopes of xenon, 129Xe and 131Xe, have non-zero intrinsic angular momenta (nuclear spins). When mixed with alkali vapor and nitrogen, their nuclear spins can be aligned along the laser beam of circularly-polarized light that is tuned to an absorption line of the alkali atoms. Typically, pure rubidium metal, heated above 100 °C, is used to produce the alkali vapor. This alignment (spin polarization) of xenon nuclei can surpass 50% of its maximum possible value, greatly exceeding the equilibrium value dictated by the Boltzmann distribution (typically 0.001% of the maximum value at room temperature, even in the strongest magnets). Such non-equilibrium alignment of spins is a temporary condition, and is called hyperpolarization. Because the 129Xe isotope has a nuclear spin value of 1/2 (and therefore the electric quadrupole moment of 129Xe nucleus must be zero), 129Xe nucleus does not experience any quadrupolar interactions during collisions with other atoms, and thus its hyperpolarization can be maintained for long periods of time even after the laser beam has been turned off and the alcali vapor removed by condensation on a room-temperature surface. The time it takes for a collection of spins to return to their equilibrium (Boltzmann) polarization is called the T1 relaxation time. For 129Xe isotope it can range from several seconds for xenon atoms dissolved in blood to several hours in the gas phase and to several days in the deeply-frozen solid xenon. In contrast, the 131Xe isotope has a nuclear spin value of 3/2, does possess a non-zero quadrupole moment, and has T1 relaxation times in the millisecond and second ranges. The hyperpolarization process (such as Spin-Exchange optical pumping described above) renders the 129Xe isotope much more detectable via magnetic resonance imaging and has been used for studies of the lungs and other tissues. It can be used, for example, to trace the flow of gases within the lungs. ## Other In nuclear energy applications, xenon is used in bubble chambers, probes, and in other areas where a high molecular weight and inert nature is desirable. Liquid xenon is being used as a medium for detecting hypothetical weakly interactive massive particles, or WIMPs. When a WIMP collides with a xenon nucleus, it should, theoretically, strip an electron and create a primary scintillation. By using xenon, this burst of energy could then be readily distinguished from similar events caused by particles such as cosmic rays. However, the XENON experiment at the Gran Sasso National Laboratory in Italy has thus far failed to find any confirmed WIMPs. Even if no WIMPs are detected though, the experiment will serve to constrain the properties of dark matter and some physics models. The current detector at this facility is five times as sensitive as other instruments world-wide, and the sensitivity will be increased by an order of magnitude in 2008. Xenon is the preferred fuel for ion propulsion of spacecraft because of its low ionization potential per atomic weight, the ability to store it as a liquid at near room temperature (but at high pressure) yet easily converts back into a gas to fuel the engine. The inert nature of xenon makes it environmentally friendly and less corrosive to an ion engine than other fuels such as mercury or caesium. Xenon was first used for satellite ion engines during the 1970s. It was later employed as a propellant for Europe's SMART-1 spacecraft and for the three ion propulsion engines on NASA's Dawn Spacecraft. Chemically, the perxenate compounds are used as oxidizing agents in analytical chemistry. Xenon difluoride is used as an etchant for silicon, particularly in the production of microelectromechanical systems (MEMS). The anticancer drug 5-fluorouracil can be produced by reacting Xenon difluoride with Uracil. Xenon is also used in protein crystallography. Applied at pressures from 0.5 to 5 MPa (5 to 50 atm) to a protein crystal, xenon atoms bind in predominantly hydrophobic cavities, often creating a high quality, isomorphous, heavy-atom derivative, which can be used for solving the phase problem. # Precautions Xenon gas can be safely kept in normal sealed glass or metal containers at standard temperature and pressure. However, it readily dissolves in most plastics and rubber, and will gradually escape from a container sealed with such materials. Xenon is non-toxic, although it does dissolve in blood and belongs to a select group of substances that penetrate the blood-brain barrier, causing mild anaesthesia when inhaled in very high concentrations (see anesthesia subsection above). Many of xenon compounds are explosive and toxic due to their strong oxidative properties. At 169 m/s, the speed of sound in xenon gas is slower than that in air (due to the slower average speed of the heavy xenon atoms compared to nitrogen and oxygen molecules), so xenon lowers the resonant frequencies of the vocal tract when inhaled. This produces a characteristic lowered voice pitch, opposite the high-pitched voice caused by inhalation of helium. Like helium, xenon does not satisfy the body's need for oxygen and is a simple asphyxiant; consequently, many universities no longer allow the voice stunt as a general chemistry demonstration. As xenon is expensive, the gas sulfur hexafluoride, which is similar to xenon in molecular weight (146 versus 131), is generally used in this stunt, although it too is an asphyxiant. It is possible to safely breathe heavy gases such as xenon or sulfur hexafluoride when they include a 20% mixture of oxygen. The lungs mix the gases very effectively and rapidly, so that the heavy gases are purged along with the oxygen and do not accumulate at the bottom of the lungs. There is, however, a danger associated with any heavy gas in large quantities: it may sit invisibly in a container, and if a person enters a container filled with an odorless, colorless gas, they may find themselves breathing it unknowingly. Xenon is rarely used in large enough quantities for this to be a concern, though the potential for danger exists any time a tank or container of xenon is kept in an unventilated space.	Xenon Template:Infobox xenon # Overview Xenon (Template:PronEng in the UK, Template:IPA in the US) is a chemical element that has the symbol Xe and atomic number 54. A colorless, heavy, odorless noble gas, xenon occurs in the earth's atmosphere in trace amounts.[1] Although generally unreactive, xenon can undergo a few chemical reactions such as the formation of xenon hexafluoroplatinate, the first noble gas compound to be synthesized.[2][3][4] Naturally occurring xenon is made of nine stable isotopes, but there are also over 40 unstable isotopes that undergo radioactive decay. The isotope ratios of xenon are an important tool for studying the early history of the Solar System.[5] Xenon-135 is produced as a result of nuclear fission and acts as a neutron absorber in nuclear reactors.[6] Xenon is used in flash lamps[7] and arc lamps,[8] and as a general anesthetic.[9] The first excimer laser design used a xenon dimer molecule (Xe2) as its lasing medium,[10] and the earliest laser designs used xenon flash lamps as pumps.[11] Xenon is also being used to search for hypothetical weakly interactive massive particles[12] and as the propellant for ion thrusters in spacecraft.[13] # History Xenon was discovered in England by William Ramsay and Morris Travers on July 12, 1898, shortly after their discovery of the elements krypton and neon. They found it in the residue left over from evaporating components of liquid air.[14][15] Ramsay suggested the name xenon for this gas from the Greek word ξένον [xenon], neuter singular form of ξένος [xenos], meaning foreign, strange, or host.[16][17] In 1902, Ramsay estimated the proportion of xenon in the Earth's atmosphere as one part in 20 million.[18] During the 1930s, the engineer Harold Edgerton began exploring strobe light technology for high-speed photography. This led him to the invention of the xenon flash lamp, in which light is generated by sending a brief electrical current through a tube filled with xenon gas. In 1934, Edgerton was able to generate flashes as brief as one microsecond with this method.[7][19][20] Albert R. Behnke Jr. began exploring the causes of "drunkenness" in deep-sea divers in 1939. He tested the effects of varying the breathing mixtures on his subjects, and discovered that this caused the divers to perceive a change in depth. From his results, he deduced that xenon gas could serve as an anesthetic. Although Lazharev, in Russia, apparently studied xenon anesthesia in 1941, the first published report confirming xenon anesthesia was in 1946 by J. H. Lawrence, who experimented on mice. Xenon was first used as a surgical anesthetic in 1951 by Stuart C. Cullen, who successfully operated on two patients.[21] In 1960, the physicist John H. Reynolds discovered that certain meteorites contained an isotopic anomaly in the form of an overabundance of xenon-129. He inferred that this was a decay product of radioactive iodine-129. As the half-life of 129I is 16 million years, this demonstrated that the meteorites were formed during the early history of the Solar System, as the 129I isotope was likely generated before the Solar System was formed.[22][23] Xenon and the other noble gases were for a long time considered to be completely chemically inert and not able to form compounds. However, while teaching at the University of British Columbia, Neil Bartlett discovered that the gas platinum hexafluoride (PtF6) was a powerful oxidizing agent that could oxidize oxygen (O2) to form dioxygenyl hexafluoroplatinate (O2+[PtF6]−).[24] Since O2 and xenon have almost the same first ionization potential, Bartlett realized that platinum hexafluoride might also be able to oxidize xenon. On March 23, 1962, he mixed the two gases and produced the first known compound of a noble gas, xenon hexafluoroplatinate.[25][4] Bartlett thought its composition to be Xe+[PtF6]−, although later work has revealed that it was probably a mixture of various xenon-containing salts.[26][27][28] Since then, many other xenon compounds have been discovered,[29] and some compounds of the noble gases argon, krypton, and radon have been identified, including argon fluorohydride (HArF),[30] krypton difluoride (KrF2),[31][32] and radon fluoride.[33] # Occurrence Xenon is a trace gas in Earth's atmosphere, occurring at 0.087±0.001 parts per million (μL/L).[34] It is also found in gases emitted from some mineral springs. Some radioactive species of xenon, for example, 133Xe and 135Xe, are produced by neutron irradiation of fissionable material within nuclear reactors.[2] Xenon is obtained commercially as a byproduct of the separation of air into oxygen and nitrogen. After this separation, generally performed by fractional distillation in a double-column plant, the liquid oxygen produced will contain small quantities of krypton and xenon. By additional fractional distillation steps, the liquid oxygen may be enriched to contain 0.1–0.2% of a krypton/xenon mixture, which is extracted either via adsorption onto silica gel or by distillation. Finally, the krypton/xenon mixture may be separated into krypton and xenon via distillation.[35][36] Extraction of a liter of xenon from the atmosphere requires 220 watt-hours of energy.[37] Worldwide production of xenon in 1998 was estimated at 5,000–7,000 m3.[38] Due to its low abundance, xenon is much more expensive than the lighter noble gases—approximate prices for the purchase of small quantities in Europe in 1999 were 10 €/L for xenon, 1 €/L for krypton, and 0.20 €/L for neon.[38] Xenon is relatively rare in the Sun's atmosphere, on Earth, and in the asteroids and comets. The atmosphere of Mars shows a similar xenon abundance to that of Earth: 0.08 parts per million.[39] However, Mars shows a higher proportion of 129Xe than the Earth or the Sun. As this isotope is generated by radioactive decay, the result may indicate that Mars lost most of its primordial atmosphere, possibly within the first 100 million years after the planet was formed.[40][41] By contrast, the planet Jupiter has an unusually high abundance of xenon in its atmosphere; about 2.6 times as much as the Sun.[42] This high abundance remains unexplained, but may have been caused by an early and rapid buildup of planetesimals—small, subplanetary bodies—before the presolar disk began to heat up.[43] (Otherwise, xenon would not have been trapped in the planetesimal ices.) Within the Solar System, the nucleon fraction for all isotopes of xenon is 1.56 × 10-8, or one part in 64 million of the total mass.[44] The problem of the low terrestrial xenon may potentially be explained by covalent bonding of xenon to oxygen within quartz, hence reducing the outgassing of xenon into the atmosphere.[45] Unlike the lower mass noble gases, the normal stellar nucleosynthesis process inside a star does not form xenon. Elements more massive than iron-56 have a net energy cost to produce through fusion, so there is no energy gain for a star to create xenon.[46] Instead, many isotopes of xenon are formed during supernova explosions.[47] # Characteristics An atom of xenon is defined as having a nucleus with 54 protons. At standard temperature and pressure, pure xenon gas has a density of 5.761 kg/m3, about 4.5 times the surface density of the Earth's atmosphere, 1.217 kg/m3.[48] As a liquid, xenon has a density of up to 3.100 g/mL, with the density maximum occurring at the triple point.[49] Under the same conditions, the density of solid xenon, 3.640 g/cm3, is larger than the average density of granite, 2.75 g/cm3.[49] Using gigapascals of pressure, xenon has been forced into a metallic phase.[50] Xenon is a member of the zero-valence elements that are called noble or inert gases. It is inert to most common chemical reactions (such as combustion, for example) because the outer valence shell is completely filled with eight electrons. This produces a stable, minimum energy configuration in which the outer electrons are tightly bound.[51] However, xenon can be oxidized by powerful oxidizing agents, and many xenon compounds have been synthesized. In a gas-filled tube, xenon emits a blue or lavenderish glow when the gas is excited by electrical discharge. Xenon emits a band of emission lines that span the visual spectrum,[52] but the most intense lines occur in the region of blue light, which produces the coloration.[53] # Isotopes Naturally occurring xenon is made of nine stable isotopes. The isotopes 124Xe, 134Xe and 136Xe are predicted to undergo double beta decay, but this has never been observed so they are considered to be stable.[54][55] Besides these stable forms, there are over 40 unstable isotopes that have been studied. 129Xe is produced by beta decay of 129I, which has a half-life of 16 million years, while 131mXe, 133Xe, 133mXe, and 135Xe are some of the fission products of both 235U and 239Pu,[56] and therefore used as indicators of nuclear explosions. The various isotopes of xenon are produced from supernova explosions,[47] red giant stars that have exhausted the hydrogen at their cores and entered the asymptotic giant branch, classical novae explosions[57] and the radioactive decay of elements such as iodine, uranium and plutonium.[56] The artificial isotope 135Xe is of considerable significance in the operation of nuclear fission reactors. 135Xe has a huge cross section for thermal neutrons, 2.6×106 barns,[6] so it acts as a neutron absorber or "poison" that can slow or stop the chain reaction after a period of operation. This was discovered in the earliest nuclear reactors built by the American Manhattan Project for plutonium production. Fortunately the designers had made provisions in the design to increase the reactor's reactivity (the number of neutrons per fission that go on to fission other atoms of nuclear fuel).[58] Under adverse conditions, relatively high concentrations of radioactive xenon isotopes may be found emanating from nuclear reactors due to the release of fission products from cracked fuel rods,[59] or fissioning of uranium in cooling water.[60] Because xenon is a tracer for two parent isotopes, xenon isotope ratios in meteorites are a powerful tool for studying the formation of the solar system. The iodine-xenon method of dating gives the time elapsed between nucleosynthesis and the condensation of a solid object from the solar nebula. Xenon isotopic ratios such as 129Xe/130Xe and 136Xe/130Xe are also a powerful tool for understanding terrestrial differentiation and early outgassing.[5] Excess 129Xe found in carbon dioxide well gases from New Mexico was believed to be from the decay of mantle-derived gases soon after Earth's formation.[61][56] # Compounds Xenon hexafluoroplatinate was the first chemical compound of xenon, synthesized in 1962.[25] Following this, many additional compounds of xenon have been discovered. These include xenon difluoride (XeF2), xenon tetrafluoride (XeF4), xenon hexafluoride (XeF6), xenon tetroxide (XeO4), and sodium perxenate (Na4XeO6). A highly explosive compound, xenon trioxide (XeO3), has also been made. Most of the more than 80[62][63] xenon compounds found to date contain electro-negative fluorine or oxygen. When other atoms are bound (such as hydrogen or carbon), they are often part of a molecule containing fluorine or oxygen.[64] Some compounds of xenon are colored but most are colorless.[62] In 1995, a group of scientists at the University of Helsinki in Finland (M. Räsänen and co-workers) announced the preparation of xenon dihydride (HXeH), and later xenon hydride-hydroxide (HXeOH), hydroxenoacetylene (HXeCCH), and other Xe-containing molecules. [65][66] Deuterated molecules, HXeOD and DXeOH, have also been produced.[67] As well as compounds where xenon forms a chemical bond, xenon can form clathrates—substances where xenon atoms are trapped by the crystalline lattice of another compound. An example is xenon hydrate (Xe·5.75 H2O), where xenon atoms occupy vacancies in a lattice of water molecules.[68] The deuterated version of this hydrate has also been produced.[69] Such clathrate hydrates can occur naturally under conditions of high pressure, such as in Lake Vostok underneath the Antarctic ice sheet.[70] Clathrate formation can be used to fractionally distill xenon, argon and krypton.[71] Xenon can also form endohedral fullerene compounds, where a xenon atom is trapped inside a fullerene molecule. The xenon atom trapped in the fullerene can be monitored via 129Xe nuclear magnetic resonance spectroscopy. Using this technique, chemical reactions on the fullerene molecule can be analyzed, due to the sensitivity of the chemical shift of the xenon atom to its environment. However, the xenon atom also has an electronic influence on the reactivity of the fullerene.[72] # Applications Although xenon is rare and relatively expensive to extract from the Earth's atmosphere, it still has a number of applications. ## Illumination and optics ### Gas-discharge lamps Xenon is used in light-emitting devices called xenon flash lamps, which are used in photographic flashes and stroboscopic lamps;[7] to excite the active medium in lasers which then generate coherent light;[73] and, occasionally, in bactericidal lamps.[74] The first solid-state laser, invented in 1960, was pumped by a xenon flash lamp,[11] and lasers used to power inertial confinement fusion are also pumped by xenon flash lamps.[75] Continuous, short-arc, high pressure xenon arc lamps have a color temperature closely approximating noon sunlight and are used in solar simulators. That is, the chromaticity of these lamps closely approximates a heated black-body radiator that has a temperature close to that observed from the Sun. After they were first introduced during the 1940s, these lamps began replacing the shorter-lived carbon arc lamps in movie projectors.[8] They are employed in typical 35mm and IMAX film projection systems, automotive HID headlights and other specialized uses. These arc lamps are an excellent source of short wavelength ultraviolet radiation and they have intense emissions in the near infrared, which is used in some night vision systems. The individual cells in a plasma display use a mixture of xenon and neon that is converted into a plasma using electrodes. The interaction of this plasma with the electrodes generates ultraviolet photons, which then excite the phosphor coating on the front of the display.[76][77] Xenon is used as a "starter gas" in high pressure sodium lamps. It has the lowest thermal conductivity and lowest ionization potential of all the non-radioactive noble gases. As a noble gas, it does not interfere with the chemical reactions occurring in the operating lamp. The low thermal conductivity minimizes thermal losses in the lamp while in the operating state, and the low ionization potential causes the breakdown voltage of the gas to be relatively low in the cold state, which allows the lamp to be more easily started.[78] ### Lasers In 1962, a group of researchers at Bell Laboratories discovered laser action in xenon,[79] and later found that the laser gain was improved by adding helium to the lasing medium.[80][81] The first excimer laser used a xenon dimer (Xe2) energized by a beam of electrons to produce stimulated emission at an ultraviolet wavelength of 176 nm.[10] Xenon chloride and xenon fluoride have also been used in excimer (or, more accurately, exciplex) lasers.[82] The xenon chloride excimer laser has been employed, for example, in certain dermatological uses.[83] ## Anesthesia Xenon has been used as a general anesthetic, although it is expensive. Even so, anesthesia machines that can deliver xenon are about to appear on the European market.[84] Two mechanisms for xenon anesthesia have been proposed. The first one involves the inhibition of the calcium ATPase pump—the mechanism cells use to remove calcium (Ca2+)—in the cell membrane of synapses.[85] This results from a conformational change when xenon binds to nonpolar sites inside the protein.[86] The second mechanism focuses on the non-specific interactions between the anesthetic and the lipid membrane.[87] Xenon has a minimum alveolar concentration (MAC) of 0.63, making it 50% more potent than N2O as an anesthetic. Thus it can be used in concentrations with oxygen that have a lower risk of hypoxia. Unlike nitrous oxide (N2O), xenon is not a greenhouse gas and so it is also viewed as environmentally friendly. Because of the high cost of xenon, however, economic application will require a closed system so that the gas can be recycled, with the gas being appropriately filtered for contaminants between uses.[37] ## Medical imaging Gamma emission from the radioisotope 133Xe of xenon can be used to image the heart, lungs, and brain, for example, by means of single photon emission computed tomography. 133Xe has also been used to measure blood flow.[88][89][90] Nuclei of only two of the stable isotopes of xenon, 129Xe and 131Xe, have non-zero intrinsic angular momenta (nuclear spins). When mixed with alkali vapor and nitrogen, their nuclear spins can be aligned along the laser beam of circularly-polarized light that is tuned to an absorption line of the alkali atoms. Typically, pure rubidium metal, heated above 100 °C, is used to produce the alkali vapor. This alignment (spin polarization) of xenon nuclei can surpass 50% of its maximum possible value, greatly exceeding the equilibrium value dictated by the Boltzmann distribution (typically 0.001% of the maximum value at room temperature, even in the strongest magnets). Such non-equilibrium alignment of spins is a temporary condition, and is called hyperpolarization. Because the 129Xe isotope has a nuclear spin value of 1/2 (and therefore the electric quadrupole moment of 129Xe nucleus must be zero), 129Xe nucleus does not experience any quadrupolar interactions during collisions with other atoms, and thus its hyperpolarization can be maintained for long periods of time even after the laser beam has been turned off and the alcali vapor removed by condensation on a room-temperature surface. The time it takes for a collection of spins to return to their equilibrium (Boltzmann) polarization is called the T1 relaxation time. For 129Xe isotope it can range from several seconds for xenon atoms dissolved in blood[91] to several hours in the gas phase[92] and to several days in the deeply-frozen solid xenon.[93] In contrast, the 131Xe isotope has a nuclear spin value of 3/2, does possess a non-zero quadrupole moment, and has T1 relaxation times in the millisecond and second ranges.[94] The hyperpolarization process (such as Spin-Exchange optical pumping described above) renders the 129Xe isotope much more detectable via magnetic resonance imaging and has been used for studies of the lungs and other tissues. It can be used, for example, to trace the flow of gases within the lungs.[95][96] ## Other In nuclear energy applications, xenon is used in bubble chambers,[97] probes, and in other areas where a high molecular weight and inert nature is desirable. Liquid xenon is being used as a medium for detecting hypothetical weakly interactive massive particles, or WIMPs. When a WIMP collides with a xenon nucleus, it should, theoretically, strip an electron and create a primary scintillation. By using xenon, this burst of energy could then be readily distinguished from similar events caused by particles such as cosmic rays.[12] However, the XENON experiment at the Gran Sasso National Laboratory in Italy has thus far failed to find any confirmed WIMPs. Even if no WIMPs are detected though, the experiment will serve to constrain the properties of dark matter and some physics models.[98] The current detector at this facility is five times as sensitive as other instruments world-wide, and the sensitivity will be increased by an order of magnitude in 2008.[99] Xenon is the preferred fuel for ion propulsion of spacecraft because of its low ionization potential per atomic weight, the ability to store it as a liquid at near room temperature (but at high pressure) yet easily converts back into a gas to fuel the engine. The inert nature of xenon makes it environmentally friendly and less corrosive to an ion engine than other fuels such as mercury or caesium. Xenon was first used for satellite ion engines during the 1970s.[100] It was later employed as a propellant for Europe's SMART-1 spacecraft[13] and for the three ion propulsion engines on NASA's Dawn Spacecraft.[101] Chemically, the perxenate compounds are used as oxidizing agents in analytical chemistry. Xenon difluoride is used as an etchant for silicon, particularly in the production of microelectromechanical systems (MEMS).[102] The anticancer drug 5-fluorouracil can be produced by reacting Xenon difluoride with Uracil.[103] Xenon is also used in protein crystallography. Applied at pressures from 0.5 to 5 MPa (5 to 50 atm) to a protein crystal, xenon atoms bind in predominantly hydrophobic cavities, often creating a high quality, isomorphous, heavy-atom derivative, which can be used for solving the phase problem.[104][105] # Precautions Xenon gas can be safely kept in normal sealed glass or metal containers at standard temperature and pressure. However, it readily dissolves in most plastics and rubber, and will gradually escape from a container sealed with such materials. Xenon is non-toxic, although it does dissolve in blood and belongs to a select group of substances that penetrate the blood-brain barrier, causing mild anaesthesia when inhaled in very high concentrations (see anesthesia subsection above). Many of xenon compounds are explosive and toxic due to their strong oxidative properties.[106] At 169 m/s, the speed of sound in xenon gas is slower than that in air[107] (due to the slower average speed of the heavy xenon atoms compared to nitrogen and oxygen molecules), so xenon lowers the resonant frequencies of the vocal tract when inhaled. This produces a characteristic lowered voice pitch, opposite the high-pitched voice caused by inhalation of helium. Like helium, xenon does not satisfy the body's need for oxygen and is a simple asphyxiant; consequently, many universities no longer allow the voice stunt as a general chemistry demonstration. As xenon is expensive, the gas sulfur hexafluoride, which is similar to xenon in molecular weight (146 versus 131), is generally used in this stunt, although it too is an asphyxiant.[108] It is possible to safely breathe heavy gases such as xenon or sulfur hexafluoride when they include a 20% mixture of oxygen. The lungs mix the gases very effectively and rapidly, so that the heavy gases are purged along with the oxygen and do not accumulate at the bottom of the lungs.[109] There is, however, a danger associated with any heavy gas in large quantities: it may sit invisibly in a container, and if a person enters a container filled with an odorless, colorless gas, they may find themselves breathing it unknowingly. Xenon is rarely used in large enough quantities for this to be a concern, though the potential for danger exists any time a tank or container of xenon is kept in an unventilated space.[110]	https://www.wikidoc.org/index.php/Xenon
da49e300d57b7cd3343041cc77454a50fd7d4b68	wikidoc	YIPF1	YIPF1 Protein YIPF1 is a protein that in humans is encoded by the YIPF1 gene. # Model organisms Model organisms have been used in the study of YIPF1 function. A conditional knockout mouse line, called Yipf1tm1a(EUCOMM)Wtsi was generated as part of the International Knockout Mouse Consortium program — a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists — at the Wellcome Trust Sanger Institute. Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion. Twenty three tests were carried out on mutant mice, however no significant abnormalities were observed.	YIPF1 Protein YIPF1 is a protein that in humans is encoded by the YIPF1 gene.[1][2] # Model organisms Model organisms have been used in the study of YIPF1 function. A conditional knockout mouse line, called Yipf1tm1a(EUCOMM)Wtsi[7][8] was generated as part of the International Knockout Mouse Consortium program — a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists — at the Wellcome Trust Sanger Institute.[9][10][11] Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion.[5][12] Twenty three tests were carried out on mutant mice, however no significant abnormalities were observed.[5]	https://www.wikidoc.org/index.php/YIPF1
33d558195ebd2e63c903e7929b2d2c313cb0ce90	wikidoc	YPEL3	YPEL3 Yippee-like 3 (Drosophila) is a protein that in humans is encoded by the YPEL3 gene. YPEL3 has growth inhibitory effects in normal and tumor cell lines. One of five family members (YPEL1-5), YPEL3 was named in reference to its Drosophila melanogaster orthologue. Initially discovered in a gene expression profiling assay of p53 activated MCF7 cells, induction of YPEL3 has been shown to trigger permanent growth arrest or cellular senescence in certain human normal and tumor cell types. DNA methylation of a CpG island near the YPEL3 promoter as well as histone acetylation may represent possible epigenetic mechanisms leading to decreased gene expression in human tumors. # Gene location and protein structure Human YPEL3 is located on the short arm of chromosome 16 (p1611.2) and covers 4.62kb from 30015754 to 30011130 on the reverse strand. The drosophilia Yippee protein was identified as a putative zinc finger motif containing protein exhibiting a high degree of conservation among the cysteines and histidines. Zinc fingers function as structural platforms for DNA binding. # Nomenclature YPEL3 was first identified as murine SUAP, named for small unstable apoptotic protein because of its apparent role in cellular growth inhibition via apoptosis when studied in myeloid precursor cell lines . SUAP later attained its current designation as YPEL3 (Yippee like three), after it was discovered to be one of five human genes possessing homology with the Drosophila Yippee protein. # Discovery The Drosophilia Yippee protein was originally discovered in a yeast interaction trap screen when it was found to physically interact with Hyalophora cecropia Hemolin. After subsequent cloning and sequencing experiments Yippee was found to be a conserved gene family of proteins present in a diverse range of eukaryotic organisms, ranging from fungi to humans. When analyzed at the amino acid level, Drosophila melanogaster Yippee and YPEL1 displayed a high level of homology (76%). During later sequence analysis of human chromosome 22, researchers identified a gene family YPEL1-YPEL5, which had high homology with the Drosophila Yippee gene. YPEL3’s role as a novel tumor suppressor and its involvement in cellular proliferation were discovered during experiments to investigate p53 dependent cell cycle arrest. While investigating the p53 tumor suppressor protein, microarray studies which targeted Hdmx and Hdm2, both p53 negative regulators, revealed YPEL3 as a potential p53 regulated gene in MCF7 breast cancer cells. Investigation into its function led to the discovery of YPEL3 being a novel protein whose growth suppressive activity is thought to be mediated through a cellular senescence pathway. # Function ## Regulation by p53 p53 is a tumor suppressor protein encoded by the human gene TP53 whose function is to prevent unregulated cell growth. p53 can be activated in response to a wide variety of cellular stressors, both oncogenic and non-oncogenic. An important checkpoint in a complex pathway, activated p53 has been shown to bind DNA and transcriptionally regulate genes that can mediate a variety of cellular growth processes including DNA repair, growth arrest, cellular senescence and apoptosis. The importance of functioning p53 in the regulation of the cell cycle is evident in that 55% of human cancers exhibit p53 mutations. YPEL3 was discovered to be a possible p53 target after a screen for such genes was performed in MCF7 breast cancer cells following RNAi knockdown of p53 negative inhibitors. In both human normal and tumor cell lines, YPEL3 has been shown to be a p53-inducible gene. Two putative p53 binding sites have been identified, one 1.3-Kbp 5' of the YPEL3 promoter and another upstream of the YPEL3 promoter. ## Cellular senescence As a part of the p53 pathway response and its anti-proliferation role, cellular senescence has gained attention for its working relationship with tumor suppressor genes. Characterized by the limited ability of cultured normal cells to divide, senescence has been shown to be triggered through oncogenic activation( premature senescence) as well as telomere shortening as the result of successive rounds of DNA replication (replicative senescence). Recognized hallmarks of cellular senescence include senescence associated(SA)beta galactosidase staining and the appearance of senescence-associated heterochromatic foci(SAHF) within the nuclei of senescent cells. Although studies in murine myeloid precursor cell lines indicated YPEL3 to have a role in apoptosis, human YPEL3 failed to demonstrate an apoptotic response using sub-G1 or poly ADP ribose polymerase cleavage as accepted indicators of programmed cell death. YPEL3 has been shown to trigger premature senescence when studied in IMR90 primary human fibroblasts. Studies in U2OS osteosarcoma cells and MCF7 breast cancer cells have also demonstrated increased cellular senescence upon YPEL3 induction. As further possible evidence to its function, reduced expression of YPEL3 has been observed in ovarian, lung, and colon tumor cell lines. ## Epigenetic modification Epigenetics is the study of changes in gene activity that do not involve alterations to genetic code, or DNA. Instead, just above the genome sits various epigenetic markers which serve to provide instructions to activate or inactivate genes to varying degrees. This silencing or activation of genes has been recognized to play an important role in the differentiation of nascent cells and several human disease states including cancer. Unlike genetic mutations, epigenetic changes are considered reversible, although further study is needed. Two common methods of epigenetic modification are DNA methylation and histone modification. Specifically, hypermethylation of CpG islands( guanine and cytosine rich spans of DNA) near the promoters of tumor suppressor genes have been documented in specific tumor cell lines. In the case of the tumor suppressors VHL (associated with von Hippel–Lindau disease), p16, hMLH1, and BRCA1(a gene associated with breast cancer susceptibility), hypermethylation of the CpG-island has been shown to be a method of gene inactivation. Both histone acetylation and DNA methylation have been studied as possible epigenetic means of regulating YPEL3 expression. When studied in Cp70 ovarian carcinoma cells, hypermethylation of a CpG island immediately upstream of the YPEL3 promoter has been seen to down regulate YPEL3 expression. Hypermethylation seen in the promoters of tumor suppressor genes are cancer type specific, allowing each tumor type to be identifiable with an individual pattern. Such discoveries have led researchers to investigate epigenetic markers as potential diagnostic tools, prognostic factors, and indicators for the responsiveness to treatment of human cancers, although continued study is needed.	YPEL3 Yippee-like 3 (Drosophila) is a protein that in humans is encoded by the YPEL3 gene.[1][2] YPEL3 has growth inhibitory effects in normal and tumor cell lines.[3] One of five family members (YPEL1-5), YPEL3 was named in reference to its Drosophila melanogaster orthologue.[2] Initially discovered in a gene expression profiling assay of p53 activated MCF7 cells,[4] induction of YPEL3 has been shown to trigger permanent growth arrest or cellular senescence in certain human normal and tumor cell types.[3] DNA methylation of a CpG island near the YPEL3 promoter as well as histone acetylation may represent possible epigenetic mechanisms leading to decreased gene expression in human tumors.[3] # Gene location and protein structure Human YPEL3 is located on the short arm of chromosome 16 (p1611.2) and covers 4.62kb from 30015754 to 30011130 on the reverse strand.[2][5] The drosophilia Yippee protein was identified as a putative zinc finger motif containing protein exhibiting a high degree of conservation among the cysteines and histidines.[6] Zinc fingers function as structural platforms for DNA binding. # Nomenclature YPEL3 was first identified as murine SUAP, named for small unstable apoptotic protein because of its apparent role in cellular growth inhibition via apoptosis when studied in myeloid precursor cell lines .[7] SUAP later attained its current designation as YPEL3 (Yippee like three), after it was discovered to be one of five human genes possessing homology with the Drosophila Yippee protein.[2] # Discovery The Drosophilia Yippee protein was originally discovered in a yeast interaction trap screen when it was found to physically interact with Hyalophora cecropia Hemolin. After subsequent cloning and sequencing experiments Yippee was found to be a conserved gene family of proteins present in a diverse range of eukaryotic organisms, ranging from fungi to humans.[6] When analyzed at the amino acid level, Drosophila melanogaster Yippee and YPEL1 displayed a high level of homology (76%). During later sequence analysis of human chromosome 22, researchers identified a gene family YPEL1-YPEL5, which had high homology with the Drosophila Yippee gene.[2] YPEL3’s role as a novel tumor suppressor and its involvement in cellular proliferation were discovered during experiments to investigate p53 dependent cell cycle arrest. While investigating the p53 tumor suppressor protein, microarray studies which targeted Hdmx and Hdm2, both p53 negative regulators, revealed YPEL3 as a potential p53 regulated gene in MCF7 breast cancer cells.[4] Investigation into its function led to the discovery of YPEL3 being a novel protein whose growth suppressive activity is thought to be mediated through a cellular senescence pathway.[3] # Function ## Regulation by p53 p53 is a tumor suppressor protein encoded by the human gene TP53 whose function is to prevent unregulated cell growth. p53 can be activated in response to a wide variety of cellular stressors, both oncogenic and non-oncogenic. An important checkpoint in a complex pathway, activated p53 has been shown to bind DNA and transcriptionally regulate genes that can mediate a variety of cellular growth processes including DNA repair, growth arrest, cellular senescence and apoptosis.[8] The importance of functioning p53 in the regulation of the cell cycle is evident in that 55% of human cancers exhibit p53 mutations.[9] YPEL3 was discovered to be a possible p53 target after a screen for such genes was performed in MCF7 breast cancer cells following RNAi knockdown of p53 negative inhibitors.[4] In both human normal and tumor cell lines, YPEL3 has been shown to be a p53-inducible gene. Two putative p53 binding sites have been identified, one 1.3-Kbp 5' of the YPEL3 promoter and another upstream of the YPEL3 promoter.[2] ## Cellular senescence As a part of the p53 pathway response and its anti-proliferation role, cellular senescence has gained attention for its working relationship with tumor suppressor genes.[10] Characterized by the limited ability of cultured normal cells to divide, senescence has been shown to be triggered through oncogenic activation( premature senescence) as well as telomere shortening as the result of successive rounds of DNA replication (replicative senescence).[11] Recognized hallmarks of cellular senescence include senescence associated(SA)beta galactosidase staining and the appearance of senescence-associated heterochromatic foci(SAHF) within the nuclei of senescent cells.[12][13] Although studies in murine myeloid precursor cell lines indicated YPEL3 to have a role in apoptosis, human YPEL3 failed to demonstrate an apoptotic response using sub-G1 or poly ADP ribose polymerase cleavage as accepted indicators of programmed cell death.[7] YPEL3 has been shown to trigger premature senescence when studied in IMR90 primary human fibroblasts. Studies in U2OS osteosarcoma cells and MCF7 breast cancer cells have also demonstrated increased cellular senescence upon YPEL3 induction.[3] As further possible evidence to its function, reduced expression of YPEL3 has been observed in ovarian, lung, and colon tumor cell lines.[3][14] ## Epigenetic modification Epigenetics is the study of changes in gene activity that do not involve alterations to genetic code, or DNA. Instead, just above the genome sits various epigenetic markers which serve to provide instructions to activate or inactivate genes to varying degrees. This silencing or activation of genes has been recognized to play an important role in the differentiation of nascent cells and several human disease states including cancer. Unlike genetic mutations, epigenetic changes are considered reversible, although further study is needed. Two common methods of epigenetic modification are DNA methylation and histone modification. Specifically, hypermethylation of CpG islands( guanine and cytosine rich spans of DNA) near the promoters of tumor suppressor genes have been documented in specific tumor cell lines. In the case of the tumor suppressors VHL (associated with von Hippel–Lindau disease), p16, hMLH1, and BRCA1(a gene associated with breast cancer susceptibility), hypermethylation of the CpG-island has been shown to be a method of gene inactivation.[15] Both histone acetylation and DNA methylation have been studied as possible epigenetic means of regulating YPEL3 expression. When studied in Cp70 ovarian carcinoma cells, hypermethylation of a CpG island immediately upstream of the YPEL3 promoter has been seen to down regulate YPEL3 expression.[3] Hypermethylation seen in the promoters of tumor suppressor genes are cancer type specific, allowing each tumor type to be identifiable with an individual pattern.[16] Such discoveries have led researchers to investigate epigenetic markers as potential diagnostic tools, prognostic factors, and indicators for the responsiveness to treatment of human cancers, although continued study is needed.[15]	https://www.wikidoc.org/index.php/YPEL3
4b56a7901e56b03c16db1e6e31df680e66b8dbd3	wikidoc	YWHAG	YWHAG 14-3-3 protein gamma is a protein that in humans is encoded by the YWHAG gene. This gene product belongs to the 14-3-3 protein family which mediate signal transduction by binding to phosphoserine-containing proteins. This highly conserved protein family is found in both plants and mammals, and this protein is 100% identical to the rat ortholog. It is induced by growth factors in human vascular smooth muscle cells, and is also highly expressed in skeletal and heart muscles, suggesting an important role for this protein in muscle tissue. It has been shown to interact with RAF1 and protein kinase C, proteins involved in various signal transduction pathways. # Interactions YWHAG has been shown to interact with C-Raf, EPB41L3, KIF1C and Stratifin.	YWHAG 14-3-3 protein gamma is a protein that in humans is encoded by the YWHAG gene.[1][2] This gene product belongs to the 14-3-3 protein family which mediate signal transduction by binding to phosphoserine-containing proteins. This highly conserved protein family is found in both plants and mammals, and this protein is 100% identical to the rat ortholog. It is induced by growth factors in human vascular smooth muscle cells, and is also highly expressed in skeletal and heart muscles, suggesting an important role for this protein in muscle tissue. It has been shown to interact with RAF1 and protein kinase C, proteins involved in various signal transduction pathways.[3] # Interactions YWHAG has been shown to interact with C-Raf,[2][4][5] EPB41L3,[4][6] KIF1C[7] and Stratifin.[8]	https://www.wikidoc.org/index.php/YWHAG
e5a6ba35a4b937f59ade39f679b339b9553a8524	wikidoc	YWHAZ	YWHAZ 14-3-3 protein zeta/delta (14-3-3ζ) is a protein that in humans is encoded by the YWHAZ gene on chromosome 8. The protein encoded by this gene is a member of the 14-3-3 protein family and a central hub protein for many signal transduction pathways. 14-3-3ζ is a major regulator of apoptotic pathways critical to cell survival and plays a key role in a number of cancers and neurodegenerative diseases. # Structure 14-3-3 proteins generally form ~30 kDa-long homo- or heterodimers. Each of the monomers are composed of 9 antiparallel alpha helices. Four alpha-helices (αC, αE, αG, and αI) form an amphipathic groove that serves as the ligand binding site, which can recognize three types of consensus binding motifs: RXX(pS/pT)XP, RXXX(pS/pT)XP, and (pS/pT)X1-2-COOH (where pS/pT represents phosphorylated serine/threonine). In addition to these primary interactions, the target protein can also bind outside the groove via secondary interactions. In particular, the crystallized structure of 14-3-3ζ forms a cup-shaped dimer when complexed with CBY. The YWHAZ gene encodes two transcript variants which differ in the 5' UTR but produce the same protein. # Function 14-3-3ζ is one of 7 members of the 14-3-3 protein family, which is ubiquitously expressed and highly conserved among plants and mammals. This protein family is known for regulating signal transduction pathways primarily through binding phosphoserine proteins, though it can also bind phosphothreonine proteins and unphosphorylated proteins. By extension, 14-3-3 proteins are involved in a wide range of biological processes, including metabolism, transcription, apoptosis, protein transport, and cell cycle regulation. This combination of dependence on phosphorylation and widespread biological impact results in dynamic regulation of multiple signalling pathways and allows for cellular adaptation to environmental changes. In particular, 14-3-3ζ is a key player in regulating cell survival and interacts with many apoptotic proteins, including Raf kinases, BAX, BAD, NOXA, and caspase-2. For the most part,14-3-3ζ negatively regulates apoptosis by binding and sequestering BAD and BAX in the cytoplasm, effectively preventing activation of proapoptotic Bcl-2 and Bcl-XL, as well as by preventing NOXA from inhibiting antiapoptotic MCL1. As a result, 14-3-3ζ functions to protect the cell from environmental stresses, such as chemotherapy-induced death, anoikis, growth factor deprivation, and hypoxia. As an example of its dynamic activity, 14-3-3ζ activates autophagy under hypoxic conditions by binding ATG9A, while it prevents autophagy under hyperglycemic conditions by binding Vps34. Furthermore, 14-3-3ζ may regulate glucose receptor trafficking in response to insulin levels through its interaction with IRS1. In addition to cell survival, 14-3-3ζ regulates cell cycle progression through various ligands and processes. For instance, 14-3-3ζ controls cellular senescence by complexing with BIS to chaperone protein folding of STAT3 and activate the signaling pathway. Also, 14-3-3ζ can negatively regulate the G2-M phase checkpoint by binding and sequestering the cyclin-dependent kinases to the cytoplasm, thus inhibiting their activity. Since 14-3-3ζ is predominantly found in the cytoplasm and binds many nuclear proteins, it likely prevents nuclear import by blocking the nuclear localization signal of target proteins. Its localization to both the cytoplasm and nucleus also suggests a role in gene expression, possibly through regulation of transcription factor activity. # Clinical Significance The14-3-3 protein zeta/delta (14-3-3ζ) is a protein (in humans encoded by the YWHAZ gene on chromosome 8) with an important apoptotic constituents. During a normal embryologic processes, or during cell injury (such as ischemia-reperfusion injury during heart attacks and strokes) or during developments and processes in cancer, an apoptotic cell undergoes structural changes including cell shrinkage, plasma membrane blebbing, nuclear condensation, and fragmentation of the DNA and nucleus. This is followed by fragmentation into apoptotic bodies that are quickly removed by phagocytes, thereby preventing an inflammatory response. It is a mode of cell death defined by characteristic morphological, biochemical and molecular changes. It was first described as a "shrinkage necrosis", and then this term was replaced by apoptosis to emphasize its role opposite mitosis in tissue kinetics. In later stages of apoptosis the entire cell becomes fragmented, forming a number of plasma membrane-bounded apoptotic bodies which contain nuclear and or cytoplasmic elements. The ultrastructural appearance of necrosis is quite different, the main features being mitochondrial swelling, plasma membrane breakdown and cellular disintegration. Apoptosis occurs in many physiological and pathological processes. It plays an important role during embryonal development as programmed cell death and accompanies a variety of normal involutional processes in which it serves as a mechanism to remove "unwanted" cells. As a major hub protein, 14-3-3ζ is involved in various diseases and disorders. For one, 14-3-3ζ plays a central role in cell proliferation and, by extension, tumor progression. The protein has been implicated in many cancers, including lung cancer, breast cancer, lymphoma, and head and neck cancer, through pathways such as mTOR, Akt, and glucose receptor trafficking. Notably, it has been associated with chemoresistance and, thus, is a promising therapeutic target for cancer treatment. So far, it stands to become a prognostic marker for breast cancer, lung cancer, head and neck cancer, and possibly gastric cancer in patients who might require more aggressive treatment. However, no statistically significant relationship was determined in hepatocellular carcinoma. In addition to cancers, 14-3-3ζ has been implicated in pathogenic infections and neurodegenerative diseases, including Creutzfeldt–Jakob disease, Parkinson’s disease, and Alzheimer’s disease (AD). 14-3-3ζ has been observed to participate in AD through its interaction with tau protein, and its expression is correlated with disease severity. The human surfactant protein A, an innate immunity molecule (encoded by two genes SFTPA1 and SFTPA2) appears to be binding with the 14-3-3 protein family. Furthermore, inhibition of 14-3-3 was correlated with lower levels of the surfactant protein indicating a relationship between surface and 14-3-3 proteins. Surfactant is an important element in the maintenance of lung and respiratory functions. A lack of surfactant is closely related to respiratory distress syndrome. Preterm neonates who exhibit neonatal respiratory distress syndrome (NRDS) exhibit a deficiency of surfactant. All together, the 14-3-3 protein may have a significant role in respiratory function and NRDS. # Interactions YWHAZ has been shown to interact with: - IRS1, - Protein phosphatase 1, - BIS, - ATG9A, - NOXA, - AKT1, - BCAR1, - BAX, - BAD, - C-Raf, - CDC25B, - GP1BA, - GP1BB, - HMGN1, - IL9R, - LIMK1, - P53, - PRKCE - PRKCZ, - TNFAIP3, - TSC2, - Tau protein, and - VIM.	YWHAZ 14-3-3 protein zeta/delta (14-3-3ζ) is a protein that in humans is encoded by the YWHAZ gene on chromosome 8.[1][2] The protein encoded by this gene is a member of the 14-3-3 protein family and a central hub protein for many signal transduction pathways.[2][3] 14-3-3ζ is a major regulator of apoptotic pathways critical to cell survival and plays a key role in a number of cancers and neurodegenerative diseases.[3][4][5][6][7] # Structure 14-3-3 proteins generally form ~30 kDa-long homo- or heterodimers.[8][9] Each of the monomers are composed of 9 antiparallel alpha helices. Four alpha-helices (αC, αE, αG, and αI) form an amphipathic groove that serves as the ligand binding site, which can recognize three types of consensus binding motifs: RXX(pS/pT)XP, RXXX(pS/pT)XP, and (pS/pT)X1-2-COOH (where pS/pT represents phosphorylated serine/threonine). In addition to these primary interactions, the target protein can also bind outside the groove via secondary interactions. In particular, the crystallized structure of 14-3-3ζ forms a cup-shaped dimer when complexed with CBY.[9] The YWHAZ gene encodes two transcript variants which differ in the 5' UTR but produce the same protein.[2] # Function 14-3-3ζ is one of 7 members of the 14-3-3 protein family, which is ubiquitously expressed and highly conserved among plants and mammals.[2][3][7][8] This protein family is known for regulating signal transduction pathways primarily through binding phosphoserine proteins, though it can also bind phosphothreonine proteins and unphosphorylated proteins.[2][3][4][7][10] By extension, 14-3-3 proteins are involved in a wide range of biological processes, including metabolism, transcription, apoptosis, protein transport, and cell cycle regulation.[4][5][7][8] This combination of dependence on phosphorylation and widespread biological impact results in dynamic regulation of multiple signalling pathways and allows for cellular adaptation to environmental changes.[4] In particular, 14-3-3ζ is a key player in regulating cell survival and interacts with many apoptotic proteins, including Raf kinases, BAX, BAD, NOXA, and caspase-2.[4][5] For the most part,14-3-3ζ negatively regulates apoptosis by binding and sequestering BAD and BAX in the cytoplasm, effectively preventing activation of proapoptotic Bcl-2 and Bcl-XL, as well as by preventing NOXA from inhibiting antiapoptotic MCL1.[5] As a result, 14-3-3ζ functions to protect the cell from environmental stresses, such as chemotherapy-induced death, anoikis, growth factor deprivation, and hypoxia. As an example of its dynamic activity, 14-3-3ζ activates autophagy under hypoxic conditions by binding ATG9A, while it prevents autophagy under hyperglycemic conditions by binding Vps34.[4] Furthermore, 14-3-3ζ may regulate glucose receptor trafficking in response to insulin levels through its interaction with IRS1.[2][4] In addition to cell survival, 14-3-3ζ regulates cell cycle progression through various ligands and processes. For instance, 14-3-3ζ controls cellular senescence by complexing with BIS to chaperone protein folding of STAT3 and activate the signaling pathway.[11] Also, 14-3-3ζ can negatively regulate the G2-M phase checkpoint by binding and sequestering the cyclin-dependent kinases to the cytoplasm, thus inhibiting their activity.[12] Since 14-3-3ζ is predominantly found in the cytoplasm and binds many nuclear proteins, it likely prevents nuclear import by blocking the nuclear localization signal of target proteins.[8] Its localization to both the cytoplasm and nucleus also suggests a role in gene expression, possibly through regulation of transcription factor activity.[5] # Clinical Significance The14-3-3 protein zeta/delta (14-3-3ζ) is a protein (in humans encoded by the YWHAZ gene on chromosome 8) with an important apoptotic constituents. During a normal embryologic processes, or during cell injury (such as ischemia-reperfusion injury during heart attacks and strokes) or during developments and processes in cancer, an apoptotic cell undergoes structural changes including cell shrinkage, plasma membrane blebbing, nuclear condensation, and fragmentation of the DNA and nucleus. This is followed by fragmentation into apoptotic bodies that are quickly removed by phagocytes, thereby preventing an inflammatory response.[13] It is a mode of cell death defined by characteristic morphological, biochemical and molecular changes. It was first described as a "shrinkage necrosis", and then this term was replaced by apoptosis to emphasize its role opposite mitosis in tissue kinetics. In later stages of apoptosis the entire cell becomes fragmented, forming a number of plasma membrane-bounded apoptotic bodies which contain nuclear and or cytoplasmic elements. The ultrastructural appearance of necrosis is quite different, the main features being mitochondrial swelling, plasma membrane breakdown and cellular disintegration. Apoptosis occurs in many physiological and pathological processes. It plays an important role during embryonal development as programmed cell death and accompanies a variety of normal involutional processes in which it serves as a mechanism to remove "unwanted" cells. As a major hub protein, 14-3-3ζ is involved in various diseases and disorders. For one, 14-3-3ζ plays a central role in cell proliferation and, by extension, tumor progression.[3][6] The protein has been implicated in many cancers, including lung cancer, breast cancer, lymphoma, and head and neck cancer, through pathways such as mTOR, Akt, and glucose receptor trafficking. Notably, it has been associated with chemoresistance and, thus, is a promising therapeutic target for cancer treatment.[4][5][6] So far, it stands to become a prognostic marker for breast cancer, lung cancer, head and neck cancer, and possibly gastric cancer in patients who might require more aggressive treatment.[3] However, no statistically significant relationship was determined in hepatocellular carcinoma.[12] In addition to cancers, 14-3-3ζ has been implicated in pathogenic infections and neurodegenerative diseases, including Creutzfeldt–Jakob disease, Parkinson’s disease, and Alzheimer’s disease (AD).[7] 14-3-3ζ has been observed to participate in AD through its interaction with tau protein, and its expression is correlated with disease severity.[10] The human surfactant protein A, an innate immunity molecule (encoded by two genes SFTPA1 and SFTPA2) appears to be binding with the 14-3-3 protein family. Furthermore, inhibition of 14-3-3 was correlated with lower levels of the surfactant protein indicating a relationship between surface and 14-3-3 proteins.[14] Surfactant is an important element in the maintenance of lung and respiratory functions. A lack of surfactant is closely related to respiratory distress syndrome. Preterm neonates who exhibit neonatal respiratory distress syndrome (NRDS) exhibit a deficiency of surfactant. All together, the 14-3-3 protein may have a significant role in respiratory function and NRDS.[15][16] # Interactions YWHAZ has been shown to interact with: - IRS1,[2] - Protein phosphatase 1,[8] - BIS,[11] - ATG9A,[4] - NOXA,[5] - AKT1,[17] - BCAR1,[18] - BAX,[5] - BAD,[5][19] - C-Raf,[20][21][22][23][24] - CDC25B,[25] - GP1BA,[26][27][28] - GP1BB,[26][27][29] - HMGN1,[30] - IL9R,[31] - LIMK1,[32] - P53,[33] - PRKCE[34] - PRKCZ,[23][35] - TNFAIP3,[36][37] - TSC2,[38] - Tau protein,[39] and - VIM.[21]	https://www.wikidoc.org/index.php/YWHAZ
8a4d669555f657e405cf48a83f06f355048f5418	wikidoc	Yeast	Yeast Yeasts are a growth form of eukaryotic micro organisms classified in the kingdom Fungi, with about 1,500 species described; they dominate fungal diversity in the oceans. Most reproduce asexually by budding, although a few do by binary fission. Yeasts are unicellular, although some species with yeast forms may become multicellular through the formation of a string of connected budding cells known as pseudohyphae, or false hyphae as seen in most molds. Yeast size can vary greatly depending on the species, typically measuring 3–4 µm in diameter, although some yeasts can reach over 40 µm. The yeast species Saccharomyces cerevisiae has been used in baking and fermenting alcoholic beverages for thousands of years. It is also extremely important as a model organism in modern cell biology research, and is the most thoroughly researched eukaryotic microorganism. Researchers have used it to gather information into the biology of the eukaryotic cell and ultimately human biology. Other species of yeast, such as Candida albicans, are opportunistic pathogens and can cause infection in humans. Yeasts have recently been used to generate electricity in microbial fuel cells, and produce ethanol for the biofuel industry. Yeasts do not form a specific taxonomic or phylogenetic grouping. At present it is estimated that only 1% of all yeast species have been described. The term "yeast" is often taken as a synonym for S. cerevisiae, however the phylogenetic diversity of yeasts is shown by their placement in both divisions Ascomycota and Basidiomycota. The budding yeasts ("true yeasts") are classified in the order Saccharomycetales. # History The word "yeast" comes from the Old English language "gist", "gyst", and ultimately from the Indo-European root "yes-", meaning boil, foam, or bubble. Yeast microbes are probably one of the earliest domesticated organisms. People have used yeast for fermentation and baking throughout history. Archaeologists digging in Egyptian ruins found early grinding stones and baking chambers for yeasted bread, as well as drawings of 4,000-year-old bakeries and breweries. In 1680 the Dutch naturalist Antoine van Leeuwenhoek first microscopically observed yeast, but at the time did not consider them to be living organisms but rather globular structures. In 1857 French microbiologist Louis Pasteur proved in the paper "Mémoire sur la fermentation alcoolique" that alcoholic fermentation was conducted by living yeasts and not by a chemical catalyst. Pasteur showed that by bubbling oxygen into the yeast broth, cell growth could be increased, but the fermentation inhibited - an observation later called the Pasteur effect. The commercial use of yeast for baking bread and similar dough-based products did not become popular in the United States until after the Centennial Exposition in 1876 in Philadelphia, where Charles L. Fleischmann exibited the product and a process to use it, as well as serving the resultant baked bread. # Growth and nutrition Yeasts are chemoorganotrophs as they use organic compounds as a source of energy and do not require sunlight to grow. The main source of carbon is obtained by hexose sugars such as glucose and fructose, or disaccharides such as sucrose and maltose. Some species can metabolize pentose sugars, alcohols, and organic acids. Yeast species either require oxygen for aerobic cellular respiration (obligate aerobes), or are anaerobic but also have aerobic methods of energy production (facultative anaerobes). Unlike bacteria, there are no known yeast species that grow only anaerobically (obligate anaerobes). Also, because they are adapted to them, yeasts grow best in a neutral pH environment. Yeasts will grow over a temperature range of 10°-37°C (50°-98.6°F), with an optimal temperature range of 30°-37°C (86°-98.6°F), depending on the type of species. S. cerevisiae works best at about 30°C. There is little activity in the range of 0°-10°C. Above 37°C yeast cells become stressed and will not divide properly. Most yeast cells die above 50°C (122°F). The cells can survive freezing under certain conditions, with viability decreasing over time. Yeasts are ubiquitous in the environment, but are most frequently isolated from sugar-rich samples. Some good examples include fruits and berries (such as grapes, apples or peaches), and exudates from plants (such as plant saps or cacti). Some yeasts are found in association with soil and insects. Yeast are generally grown in the laboratory on solid growth media or liquid broths. Common media used for the cultivation of yeasts include; potato dextrose agar (PDA) or potato dextrose broth, Wallerstien Laboratories Nutrient agar (WLN), Yeast Peptone Dextrose agar (YPD), and Yeast Mould agar or broth (YM). The antibiotic cycloheximide is sometimes added to yeast growth media to inhibit the growth of Saccharomyces yeasts and select for wild/indigenous yeast species. # Reproduction Yeasts have asexual and sexual reproductive cycles; however the most common mode of vegetative growth in yeast is asexual reproduction by budding or fission. Here a small bud, or daughter cell, is formed on the parent cell. The nucleus of the parent cell splits into a daughter nucleus and migrates into the daughter cell. The bud continues to grow until it separates from the parent cell, forming a new cell. The bud can develop on different parts of the parent cell depending on the genus of the yeast.Yeast needs the exact chemical form of sugar and cannot reproduce with sugar substitutes. However if the sugar substitute's chemical form is similar to sugar, yeast will reproduce a bit compared with many sugar substitutes where yeast will not reproduce at all. Under high stress conditions haploid cells will generally die, however under the same conditions diploid cells can undergo sporulation, entering sexual reproduction (meiosis) and producing a variety of haploid spores, which can go on to mate (conjugate), reforming the diploid. Yeast of the species Schizosaccharomyces pombe reproduce by binary fission instead of budding. # Uses The useful physiological properties of yeast have led to their use in the field of biotechnology. Fermentation of sugars by yeast is the oldest and largest application of this technology. Many types of yeasts are used for making many foods: Baker's yeast in bread production, brewer's yeast in beer fermentation, yeast in wine fermentation and for xylitol production. Yeasts are also one of the most widely used model organisms for genetics and cell biology. ## Alcoholic beverages Alcoholic beverages are loosely defined as a beverage that contains ethanol (C2H5OH). This ethanol is almost always produced by fermentation - the metabolism of carbohydrates by certain species of yeast. Beverages such as wine, beer, or distilled spirits all use yeast at some stage of their production. ### Beer Beer brewers classify yeasts as top-fermenting and bottom-fermenting. This distinction was introduced by the Dane Emil Christian Hansen. Top-fermenting yeasts are so called because they form a foam at the top of the wort during fermentation. They can produce higher alcohol concentrations and prefer higher temperatures, producing fruitier ale-type beers. An example of a top-fermenting yeast is Saccharomyces cerevisiae, known to brewers as ale yeast. Bottom-fermenting yeasts are used to produce lager-type beers. These yeasts ferment more sugars, leaving a crisper taste, and grow well at low temperatures. An example of a bottom-fermenting yeast is Saccharomyces pastorianus. For both types, yeast is fully distributed through the beer while it is fermenting, and both equally flocculate (clump together and precipitate to the bottom of the vessel) when it is finished. By no means do all top-fermenting yeasts demonstrate this behaviour, but it features strongly in many English ale yeasts which may also exhibit chain forming (the failure of budded cells to break from the mother cell) which is technically different from true flocculation. Lambic, a style of Belgian beer, is fermented spontaneously by wild yeasts primarily of the genus Brettanomyces. In industrial brewing, to ensure purity of strain, a 'clean' sample of the yeast is stored refrigerated in a laboratory. After a certain number of fermentation cycles, a full scale propagation is produced from this laboratory sample. Typically, it is grown up in about three or four stages using sterile brewing wort and oxygen. ### Root Beer and Sodas Root beer and other sweet carbonated beverages can be produced using the same methods as beer, except that fermentation is stopped sooner, producing carbon dioxide, but only trace amounts of alcohol, and a significant amount of sugar is left in the drink. ### Distilled beverages A distilled beverage is a beverage that contains ethanol that has been purified by distillation. Carbohydrate-containing plant material is fermented by yeast, producing a dilute solution of ethanol in the process. Spirits such as whiskey and rum are prepared by distilling these dilute solutions of ethanol. Components other than ethanol are collected in the condensate, including water, esters, and other alcohols which account for the flavor of the beverage. ### Wine Yeast is used in winemaking where it converts the sugars present in grape juice or must into alcohol. Yeast is normally already invisibly present on the grapes. The fermentation can be done with this endogenous (or wild) yeast; however, this may give unpredictable results depending on the exact types of yeast species that are present. For this reason a pure yeast culture is generally added to the must, which rapidly predominates the fermentation as it proceeds. This represses the wild yeasts and ensures a reliable and predictable fermentation. Most added wine yeasts are strains of Saccharomyces cerevisiae, however not all strains of the species are suitable. Different S. cerevisiae yeast strains have differing physiological and fermentative properties, therefore the actual strain of yeast selected can have a direct impact on the finished wine. Significant research has been undertaken into the development of novel wine yeast strains that produce atypical flavour profiles or increased complexity in wines. The growth of some yeasts such as Zygosaccharomyces and Brettanomyces in wine can result in wine faults and subsequent spoilage. Brettanomyces produces an array of metabolites when growing in wine, some of which are volatile phenolic compounds. Together these compounds are often referred to as "Brettanomyces character", and are often described as antiseptic or "barnyard" type aromas. Brettanomyces is a significant contributor to wine faults within the wine industry. ## Baking Yeast, most commonly Saccharomyces cerevisiae, is used in baking as a leavening agent, where it converts the fermentable sugars present in the dough into carbon dioxide. This causes the dough to expand or rise as the carbon dioxide forms pockets or bubbles. When the dough is baked it "sets" and the pockets remain, giving the baked product a soft and spongy texture. The use of potatoes, water from potato boiling, eggs, or sugar in a bread dough accelerates the growth of yeasts. Salt and fats such as butter slow down yeast growth. The majority of the yeast used in baking is of the same species common in alcoholic fermentation. Additionally, Saccharomyces exiguus (also known as S. minor) is a wild yeast found on plants, fruits, and grains that is occasionally used for baking. Sugar and vinegar are the best conditions for yeast to ferment. It is not known when yeast was first used to bake bread. The first records that show this use came from Ancient Egypt. Researchers speculate that a mixture of flour meal and water was left longer than usual on a warm day and the yeasts that occur in natural contaminants of the flour caused it to ferment before baking. The resulting bread would have been lighter and more tasty than the normal flat, hard cake. Today there are several retailers of baker's yeast; one of the best-known is Fleischmann’s Yeast, which was developed in 1868. During World War II Fleischmann's developed a granulated active dry yeast, which did not require refrigeration and had a longer shelf life than fresh yeast. The company created yeast that would rise twice as fast, cutting down on baking time. Baker's yeast is also sold as a fresh yeast compressed into a square "cake". This form perishes quickly, and must be used soon after production in order to maintain viability. A weak solution of water and sugar can be used to determine if yeast is expired. When dissolved in the solution, active yeast will foam and bubble as it ferments the sugar into ethanol and carbon dioxide. Some recipes refer to this as proofing the yeast as it gives proof of the viability of the yeast before the other ingredients are added. When using a sourdough starter, flour and water are added instead of sugar and this is referred to as proofing the sponge. When yeast is used for making bread, it is mixed with flour, salt, and warm water (or milk). The dough is kneaded until it is smooth, and then left to rise, sometimes until it has doubled in size. Some bread doughs are knocked back after one rising and left to rise again. A longer rising time gives a better flavour, but the yeast can fail to raise the bread in the final stages if it is left for too long initially. The dough is then shaped into loaves, left to rise until it is the correct size, and then baked. Dried yeast is usually specified for use in a bread machine, however a (wet) sourdough starter can also work. ## Bioremediation Some yeasts can find potential application in the field of bioremediation. One such yeast Yarrowia lipolytica is known to degrade palm oil mill effluent, TNT (an explosive material), and other hydrocarbons such as alkanes, fatty acids, fats and oils. ## Industrial ethanol production The ability of yeast to convert sugar into ethanol has been harnessed by the biotechnology industry, which has various uses including ethanol fuel. The process starts by milling a feedstock, such as sugar cane, sweetcorn, or cheap cereal grains, and then adding dilute sulfuric acid, or fungal alpha amylase enzymes, to break down the starches into complex sugars. A gluco amylase is then added to break the complex sugars down into simple sugars. After this, yeasts are added to convert the simple sugars to ethanol, which is then distilled off to obtain ethanol up to 96% in concentration. Saccharomyces yeasts have been genetically engineered to ferment xylose, one of the major fermentable sugars present in cellulosic biomasses, such as agriculture residues, paper wastes, and wood chips. Such a development means that ethanol can be efficiently produced from more inexpensive feedstocks, making cellulosic ethanol fuel a more competitively priced alternative to gasoline fuels. ## Kombucha Yeast in symbiosis with acetic acid bacteria is used in the preparation of Kombucha, a fermented sweetened tea. Species of yeast found in the tea can vary, and may include: Brettanomyces bruxellensis, Candida stellata, Schizosaccharomyces pombe, Torulaspora delbrueckii and Zygosaccharomyces bailii. ## Nutritional supplements Yeast is used in nutritional supplements popular with vegans and the health conscious, where it is often referred to as "nutritional yeast". It is a deactivated yeast, usually Saccharomyces cerevisiae. It is an excellent source of protein and vitamins, especially the B-complex vitamins, whose functions are related to metabolism as well as other minerals and cofactors required for growth. It is also naturally low in fat and sodium. Some brands of nutritional yeast, though not all, are fortified with vitamin B12, which is produced separately from bacteria. Nutritional yeast, though it has a similar appearance to brewer's yeast, is very different and has a very different taste. Nutritional yeast has a nutty, cheesy, creamy flavor which makes it popular as an ingredient in cheese substitutes. It is often used by vegans in place of parmesan cheese. Another popular use is as a topping for popcorn. Some movie theaters are beginning to offer it along with salt or cayenne pepper as a popcorn condiment. It comes in the form of flakes, or as a yellow powder similar in texture to cornmeal, and can be found in the bulk aisle of most natural food stores. In Australia it is sometimes sold as "savory yeast flakes". Though "nutritional yeast" usually refers to commercial products, inadequately fed prisoners have used "home-grown" yeast to prevent vitamin deficiency. ## Probiotics Some probiotic supplements use the yeast Saccharomyces boulardii to maintain and restore the natural flora in the large and small gastrointestinal tract. S. boulardii has been shown to reduce the symptoms of acute diarrhea in children, prevent reinfection of Clostridium difficile, reduce bowel movements in diarrhea predominant IBS patients, and reduce the incidence of antibiotic, traveler's, and HIV/AIDS associated diarrheas. ## Science Several yeasts, particularly Saccharomyces cerevisiae, have been widely used in genetics and cell biology. This is largely because the cell cycle in a yeast cell is very similar to the cell cycle in humans, and therefore the basic cellular mechanics of DNA replication, recombination, cell division and metabolism are comparable. Also many proteins important in human biology were first discovered by studying their homologs in yeast; these proteins include cell cycle proteins, signaling proteins, and protein-processing enzymes. On 24 April 1996 S. cerevisiae was announced to be the first eukaryote to have its genome, consisting of 12 million base pairs, fully sequenced as part of the Genome project. At the time it was the most complex organism to have its full genome sequenced and took 7 years and the involvement of more than 100 laboratories to accomplish. The second yeast species to have its genome sequenced was Schizosaccharomyces pombe, which was completed in 2002. It was the 6th eukaryotic genome sequenced and consists of 13.8 million base pairs. ## Yeast extract Yeast extract is the common name for various forms of processed yeast products that are used as food additives or flavours. They are often used in the same way that monosodium glutamate (MSG) is used, and like MSG, often contain free glutamic acids. The general method for making yeast extract for food products such as Vegemite and Marmite on a commercial scale is to add salt to a suspension of yeast making the solution hypertonic, which leads to the cells shrivelling up. This triggers autolysis, where the yeast's digestive enzymes break their own proteins down into simpler compounds, a process of self-destruction. The dying yeast cells are then heated to complete their breakdown, after which the husks (yeast with thick cell walls which would give poor texture) are separated. Yeast autolysates are used in Vegemite and Promite (Australia); Marmite, Bovril and Oxo (the United Kingdom, Republic of Ireland and South Africa); and Cenovis (Switzerland). # Pathogenic yeasts Some species of yeast are opportunistic pathogens where they can cause infection in people with compromised immune systems. Cryptococcus neoformans is a significant pathogen of immunocompromised people causing the disease termed Cryptococcosis. This disease occurs in about 7–8% of AIDS patients in the USA, and a slightly smaller percentage (3–6%) in western Europe. The cells of the yeast are surrounded by a rigid polysaccharide capsule, which helps to prevent them from being recognised and engulfed by white blood cells in the human body. Yeasts of the Candida genus are another group of opportunistic pathogens which causes oral and vaginal infections in humans, known as Candidiasis. Candida is commonly found as a commensal yeast in the mucus membranes of humans and other warm-blooded animals. However, sometimes these same strains can become pathogenic. Here the yeast cells sprout a hyphal outgrowth, which locally penetrates the mucosal membrane, causing irritation and shedding of the tissues. The pathogenic yeasts of candidiasis in probable descending order of virulence for humans are: C. albicans, C. tropicalis, C. stellatoidea, C. glabrata, C. krusei, C. parapsilosis, C. guilliermondii, C. viswanathii, C. lusitaniae and Rhodotorula mucilaginosa. Candida glabrata is the second most common Candida pathogen after C. albicans, causing infections of the urogenital tract, and of the bloodstream (Candidemia). Non-pathogenic yeast such as S. cerevisiae are also implicated in disease; anti saccharomyces cerevisiae antibodies (ASCA) have been found at relatively high frequencies in familial crohn's disease and at higher frequencies in other forms of colitis. # Food spoilage Yeasts are able to grow in foods with a low pH, (5.0 or lower) and in the presence of sugars, organic acids and other easily metabolized carbon sources. During their growth, yeasts metabolize some food components and produce metabolic end products. This causes the physical, chemical, and sensory properties of a food to change, and the food is spoiled. The growth of yeast within food products is often seen on their surface, as in cheeses or meats, or by the fermentation of sugars in beverages, such as juices, and semi-liquid products, such as syrups and jams. The yeast of the Zygosaccharomyces genus have had a long history as a spoilage yeast within the food industry. This is mainly due to the fact that these species can grow in the presence of high sucrose, ethanol, acetic acid, sorbic acid, benzoic acid, and sulfur dioxide concentrations, representing some of the commonly used food preservation methods. Methylene Blue is used to test for the presence of live yeast cells.	Yeast Yeasts are a growth form of eukaryotic micro organisms classified in the kingdom Fungi, with about 1,500 species described;[1] they dominate fungal diversity in the oceans.[2] Most reproduce asexually by budding, although a few do by binary fission. Yeasts are unicellular, although some species with yeast forms may become multicellular through the formation of a string of connected budding cells known as pseudohyphae, or false hyphae as seen in most molds.[3] Yeast size can vary greatly depending on the species, typically measuring 3–4 µm in diameter, although some yeasts can reach over 40 µm.[4] The yeast species Saccharomyces cerevisiae has been used in baking and fermenting alcoholic beverages for thousands of years. It is also extremely important as a model organism in modern cell biology research, and is the most thoroughly researched eukaryotic microorganism. Researchers have used it to gather information into the biology of the eukaryotic cell and ultimately human biology.[5] Other species of yeast, such as Candida albicans, are opportunistic pathogens and can cause infection in humans. Yeasts have recently been used to generate electricity in microbial fuel cells,[6] and produce ethanol for the biofuel industry. Yeasts do not form a specific taxonomic or phylogenetic grouping. At present it is estimated that only 1% of all yeast species have been described.[7] The term "yeast" is often taken as a synonym for S. cerevisiae,[8] however the phylogenetic diversity of yeasts is shown by their placement in both divisions Ascomycota and Basidiomycota. The budding yeasts ("true yeasts") are classified in the order Saccharomycetales.[9] # History The word "yeast" comes from the Old English language "gist", "gyst", and ultimately from the Indo-European root "yes-", meaning boil, foam, or bubble.[10] Yeast microbes are probably one of the earliest domesticated organisms. People have used yeast for fermentation and baking throughout history. Archaeologists digging in Egyptian ruins found early grinding stones and baking chambers for yeasted bread, as well as drawings of 4,000-year-old bakeries and breweries.[11] In 1680 the Dutch naturalist Antoine van Leeuwenhoek first microscopically observed yeast, but at the time did not consider them to be living organisms but rather globular structures.[12] In 1857 French microbiologist Louis Pasteur proved in the paper "Mémoire sur la fermentation alcoolique" that alcoholic fermentation was conducted by living yeasts and not by a chemical catalyst.[11][13] Pasteur showed that by bubbling oxygen into the yeast broth, cell growth could be increased, but the fermentation inhibited - an observation later called the Pasteur effect. The commercial use of yeast for baking bread and similar dough-based products did not become popular in the United States until after the Centennial Exposition in 1876 in Philadelphia, where Charles L. Fleischmann exibited the product and a process to use it, as well as serving the resultant baked bread. # Growth and nutrition Yeasts are chemoorganotrophs as they use organic compounds as a source of energy and do not require sunlight to grow. The main source of carbon is obtained by hexose sugars such as glucose and fructose, or disaccharides such as sucrose and maltose. Some species can metabolize pentose sugars, alcohols, and organic acids. Yeast species either require oxygen for aerobic cellular respiration (obligate aerobes), or are anaerobic but also have aerobic methods of energy production (facultative anaerobes). Unlike bacteria, there are no known yeast species that grow only anaerobically (obligate anaerobes). Also, because they are adapted to them, yeasts grow best in a neutral pH environment. Yeasts will grow over a temperature range of 10°-37°C (50°-98.6°F), with an optimal temperature range of 30°-37°C (86°-98.6°F), depending on the type of species. S. cerevisiae works best at about 30°C. There is little activity in the range of 0°-10°C. Above 37°C yeast cells become stressed and will not divide properly. Most yeast cells die above 50°C (122°F). The cells can survive freezing under certain conditions, with viability decreasing over time. Yeasts are ubiquitous in the environment, but are most frequently isolated from sugar-rich samples. Some good examples include fruits and berries (such as grapes, apples or peaches), and exudates from plants (such as plant saps or cacti). Some yeasts are found in association with soil and insects.[14][15] Yeast are generally grown in the laboratory on solid growth media or liquid broths. Common media used for the cultivation of yeasts include; potato dextrose agar (PDA) or potato dextrose broth, Wallerstien Laboratories Nutrient agar (WLN), Yeast Peptone Dextrose agar (YPD), and Yeast Mould agar or broth (YM). The antibiotic cycloheximide is sometimes added to yeast growth media to inhibit the growth of Saccharomyces yeasts and select for wild/indigenous yeast species. # Reproduction Yeasts have asexual and sexual reproductive cycles; however the most common mode of vegetative growth in yeast is asexual reproduction by budding or fission.[16] Here a small bud, or daughter cell, is formed on the parent cell. The nucleus of the parent cell splits into a daughter nucleus and migrates into the daughter cell. The bud continues to grow until it separates from the parent cell, forming a new cell.[17] The bud can develop on different parts of the parent cell depending on the genus of the yeast.Yeast needs the exact chemical form of sugar and cannot reproduce with sugar substitutes. However if the sugar substitute's chemical form is similar to sugar, yeast will reproduce a bit compared with many sugar substitutes where yeast will not reproduce at all. Under high stress conditions haploid cells will generally die, however under the same conditions diploid cells can undergo sporulation, entering sexual reproduction (meiosis) and producing a variety of haploid spores, which can go on to mate (conjugate), reforming the diploid.[18] Yeast of the species Schizosaccharomyces pombe reproduce by binary fission instead of budding.[16] # Uses The useful physiological properties of yeast have led to their use in the field of biotechnology. Fermentation of sugars by yeast is the oldest and largest application of this technology. Many types of yeasts are used for making many foods: Baker's yeast in bread production, brewer's yeast in beer fermentation, yeast in wine fermentation and for xylitol[19] production. Yeasts are also one of the most widely used model organisms for genetics and cell biology. ## Alcoholic beverages Alcoholic beverages are loosely defined as a beverage that contains ethanol (C2H5OH). This ethanol is almost always produced by fermentation - the metabolism of carbohydrates by certain species of yeast. Beverages such as wine, beer, or distilled spirits all use yeast at some stage of their production. ### Beer Beer brewers classify yeasts as top-fermenting and bottom-fermenting. This distinction was introduced by the Dane Emil Christian Hansen. Top-fermenting yeasts are so called because they form a foam at the top of the wort during fermentation. They can produce higher alcohol concentrations and prefer higher temperatures, producing fruitier ale-type beers. An example of a top-fermenting yeast is Saccharomyces cerevisiae, known to brewers as ale yeast. Bottom-fermenting yeasts are used to produce lager-type beers. These yeasts ferment more sugars, leaving a crisper taste, and grow well at low temperatures. An example of a bottom-fermenting yeast is Saccharomyces pastorianus. For both types, yeast is fully distributed through the beer while it is fermenting, and both equally flocculate (clump together and precipitate to the bottom of the vessel) when it is finished. By no means do all top-fermenting yeasts demonstrate this behaviour, but it features strongly in many English ale yeasts which may also exhibit chain forming (the failure of budded cells to break from the mother cell) which is technically different from true flocculation. Lambic, a style of Belgian beer, is fermented spontaneously by wild yeasts primarily of the genus Brettanomyces. In industrial brewing, to ensure purity of strain, a 'clean' sample of the yeast is stored refrigerated in a laboratory. After a certain number of fermentation cycles, a full scale propagation is produced from this laboratory sample. Typically, it is grown up in about three or four stages using sterile brewing wort and oxygen. ### Root Beer and Sodas Root beer and other sweet carbonated beverages can be produced using the same methods as beer, except that fermentation is stopped sooner, producing carbon dioxide, but only trace amounts of alcohol, and a significant amount of sugar is left in the drink. ### Distilled beverages A distilled beverage is a beverage that contains ethanol that has been purified by distillation. Carbohydrate-containing plant material is fermented by yeast, producing a dilute solution of ethanol in the process. Spirits such as whiskey and rum are prepared by distilling these dilute solutions of ethanol. Components other than ethanol are collected in the condensate, including water, esters, and other alcohols which account for the flavor of the beverage. ### Wine Yeast is used in winemaking where it converts the sugars present in grape juice or must into alcohol. Yeast is normally already invisibly present on the grapes. The fermentation can be done with this endogenous (or wild) yeast;[20] however, this may give unpredictable results depending on the exact types of yeast species that are present. For this reason a pure yeast culture is generally added to the must, which rapidly predominates the fermentation as it proceeds. This represses the wild yeasts and ensures a reliable and predictable fermentation.[21] Most added wine yeasts are strains of Saccharomyces cerevisiae, however not all strains of the species are suitable.[21] Different S. cerevisiae yeast strains have differing physiological and fermentative properties, therefore the actual strain of yeast selected can have a direct impact on the finished wine.[22] Significant research has been undertaken into the development of novel wine yeast strains that produce atypical flavour profiles or increased complexity in wines.[23][24] The growth of some yeasts such as Zygosaccharomyces and Brettanomyces in wine can result in wine faults and subsequent spoilage.[25] Brettanomyces produces an array of metabolites when growing in wine, some of which are volatile phenolic compounds. Together these compounds are often referred to as "Brettanomyces character", and are often described as antiseptic or "barnyard" type aromas. Brettanomyces is a significant contributor to wine faults within the wine industry.[26] ## Baking Yeast, most commonly Saccharomyces cerevisiae, is used in baking as a leavening agent, where it converts the fermentable sugars present in the dough into carbon dioxide. This causes the dough to expand or rise as the carbon dioxide forms pockets or bubbles. When the dough is baked it "sets" and the pockets remain, giving the baked product a soft and spongy texture. The use of potatoes, water from potato boiling, eggs, or sugar in a bread dough accelerates the growth of yeasts. Salt and fats such as butter slow down yeast growth. The majority of the yeast used in baking is of the same species common in alcoholic fermentation. Additionally, Saccharomyces exiguus (also known as S. minor) is a wild yeast found on plants, fruits, and grains that is occasionally used for baking. Sugar and vinegar are the best conditions for yeast to ferment. It is not known when yeast was first used to bake bread. The first records that show this use came from Ancient Egypt.[27] Researchers speculate that a mixture of flour meal and water was left longer than usual on a warm day and the yeasts that occur in natural contaminants of the flour caused it to ferment before baking. The resulting bread would have been lighter and more tasty than the normal flat, hard cake. Today there are several retailers of baker's yeast; one of the best-known is Fleischmann’s Yeast, which was developed in 1868. During World War II Fleischmann's developed a granulated active dry yeast, which did not require refrigeration and had a longer shelf life than fresh yeast. The company created yeast that would rise twice as fast, cutting down on baking time. Baker's yeast is also sold as a fresh yeast compressed into a square "cake". This form perishes quickly, and must be used soon after production in order to maintain viability. A weak solution of water and sugar can be used to determine if yeast is expired. When dissolved in the solution, active yeast will foam and bubble as it ferments the sugar into ethanol and carbon dioxide. Some recipes refer to this as proofing the yeast as it gives proof of the viability of the yeast before the other ingredients are added. When using a sourdough starter, flour and water are added instead of sugar and this is referred to as proofing the sponge. When yeast is used for making bread, it is mixed with flour, salt, and warm water (or milk). The dough is kneaded until it is smooth, and then left to rise, sometimes until it has doubled in size. Some bread doughs are knocked back after one rising and left to rise again. A longer rising time gives a better flavour, but the yeast can fail to raise the bread in the final stages if it is left for too long initially. The dough is then shaped into loaves, left to rise until it is the correct size, and then baked. Dried yeast is usually specified for use in a bread machine, however a (wet) sourdough starter can also work. ## Bioremediation Some yeasts can find potential application in the field of bioremediation. One such yeast Yarrowia lipolytica is known to degrade palm oil mill effluent,[28] TNT (an explosive material),[29] and other hydrocarbons such as alkanes, fatty acids, fats and oils.[30] ## Industrial ethanol production The ability of yeast to convert sugar into ethanol has been harnessed by the biotechnology industry, which has various uses including ethanol fuel. The process starts by milling a feedstock, such as sugar cane, sweetcorn, or cheap cereal grains, and then adding dilute sulfuric acid, or fungal alpha amylase enzymes, to break down the starches into complex sugars. A gluco amylase is then added to break the complex sugars down into simple sugars. After this, yeasts are added to convert the simple sugars to ethanol, which is then distilled off to obtain ethanol up to 96% in concentration.[31] Saccharomyces yeasts have been genetically engineered to ferment xylose, one of the major fermentable sugars present in cellulosic biomasses, such as agriculture residues, paper wastes, and wood chips.[32] Such a development means that ethanol can be efficiently produced from more inexpensive feedstocks, making cellulosic ethanol fuel a more competitively priced alternative to gasoline fuels.[33] ## Kombucha Yeast in symbiosis with acetic acid bacteria is used in the preparation of Kombucha, a fermented sweetened tea. Species of yeast found in the tea can vary, and may include: Brettanomyces bruxellensis, Candida stellata, Schizosaccharomyces pombe, Torulaspora delbrueckii and Zygosaccharomyces bailii.[34] ## Nutritional supplements Yeast is used in nutritional supplements popular with vegans and the health conscious, where it is often referred to as "nutritional yeast". It is a deactivated yeast, usually Saccharomyces cerevisiae. It is an excellent source of protein and vitamins, especially the B-complex vitamins, whose functions are related to metabolism as well as other minerals and cofactors required for growth. It is also naturally low in fat and sodium. Some brands of nutritional yeast, though not all, are fortified with vitamin B12, which is produced separately from bacteria. Nutritional yeast, though it has a similar appearance to brewer's yeast, is very different and has a very different taste. Nutritional yeast has a nutty, cheesy, creamy flavor which makes it popular as an ingredient in cheese substitutes. It is often used by vegans in place of parmesan cheese. Another popular use is as a topping for popcorn. Some movie theaters are beginning to offer it along with salt or cayenne pepper as a popcorn condiment. It comes in the form of flakes, or as a yellow powder similar in texture to cornmeal, and can be found in the bulk aisle of most natural food stores. In Australia it is sometimes sold as "savory yeast flakes". Though "nutritional yeast" usually refers to commercial products, inadequately fed prisoners have used "home-grown" yeast to prevent vitamin deficiency.[35] ## Probiotics Some probiotic supplements use the yeast Saccharomyces boulardii to maintain and restore the natural flora in the large and small gastrointestinal tract. S. boulardii has been shown to reduce the symptoms of acute diarrhea in children,[36][37] prevent reinfection of Clostridium difficile,[38] reduce bowel movements in diarrhea predominant IBS patients,[39] and reduce the incidence of antibiotic,[40] traveler's,[41] and HIV/AIDS[42] associated diarrheas. ## Science Several yeasts, particularly Saccharomyces cerevisiae, have been widely used in genetics and cell biology. This is largely because the cell cycle in a yeast cell is very similar to the cell cycle in humans, and therefore the basic cellular mechanics of DNA replication, recombination, cell division and metabolism are comparable.[9] Also many proteins important in human biology were first discovered by studying their homologs in yeast; these proteins include cell cycle proteins, signaling proteins, and protein-processing enzymes. On 24 April 1996 S. cerevisiae was announced to be the first eukaryote to have its genome, consisting of 12 million base pairs, fully sequenced as part of the Genome project.[43] At the time it was the most complex organism to have its full genome sequenced and took 7 years and the involvement of more than 100 laboratories to accomplish.[44] The second yeast species to have its genome sequenced was Schizosaccharomyces pombe, which was completed in 2002.[45] It was the 6th eukaryotic genome sequenced and consists of 13.8 million base pairs. ## Yeast extract Yeast extract is the common name for various forms of processed yeast products that are used as food additives or flavours. They are often used in the same way that monosodium glutamate (MSG) is used, and like MSG, often contain free glutamic acids. The general method for making yeast extract for food products such as Vegemite and Marmite on a commercial scale is to add salt to a suspension of yeast making the solution hypertonic, which leads to the cells shrivelling up. This triggers autolysis, where the yeast's digestive enzymes break their own proteins down into simpler compounds, a process of self-destruction. The dying yeast cells are then heated to complete their breakdown, after which the husks (yeast with thick cell walls which would give poor texture) are separated. Yeast autolysates are used in Vegemite and Promite (Australia); Marmite, Bovril and Oxo (the United Kingdom, Republic of Ireland and South Africa); and Cenovis (Switzerland). # Pathogenic yeasts Some species of yeast are opportunistic pathogens where they can cause infection in people with compromised immune systems. Cryptococcus neoformans is a significant pathogen of immunocompromised people causing the disease termed Cryptococcosis. This disease occurs in about 7–8% of AIDS patients in the USA, and a slightly smaller percentage (3–6%) in western Europe.[46] The cells of the yeast are surrounded by a rigid polysaccharide capsule, which helps to prevent them from being recognised and engulfed by white blood cells in the human body. Yeasts of the Candida genus are another group of opportunistic pathogens which causes oral and vaginal infections in humans, known as Candidiasis. Candida is commonly found as a commensal yeast in the mucus membranes of humans and other warm-blooded animals. However, sometimes these same strains can become pathogenic. Here the yeast cells sprout a hyphal outgrowth, which locally penetrates the mucosal membrane, causing irritation and shedding of the tissues.[46] The pathogenic yeasts of candidiasis in probable descending order of virulence for humans are: C. albicans, C. tropicalis, C. stellatoidea, C. glabrata, C. krusei, C. parapsilosis, C. guilliermondii, C. viswanathii, C. lusitaniae and Rhodotorula mucilaginosa.[47] Candida glabrata is the second most common Candida pathogen after C. albicans, causing infections of the urogenital tract, and of the bloodstream (Candidemia).[48] Non-pathogenic yeast such as S. cerevisiae are also implicated in disease; anti saccharomyces cerevisiae antibodies (ASCA) have been found at relatively high frequencies in familial crohn's disease and at higher frequencies in other forms of colitis.[49] # Food spoilage Yeasts are able to grow in foods with a low pH, (5.0 or lower) and in the presence of sugars, organic acids and other easily metabolized carbon sources.[50] During their growth, yeasts metabolize some food components and produce metabolic end products. This causes the physical, chemical, and sensory properties of a food to change, and the food is spoiled.[51] The growth of yeast within food products is often seen on their surface, as in cheeses or meats, or by the fermentation of sugars in beverages, such as juices, and semi-liquid products, such as syrups and jams.[50] The yeast of the Zygosaccharomyces genus have had a long history as a spoilage yeast within the food industry. This is mainly due to the fact that these species can grow in the presence of high sucrose, ethanol, acetic acid, sorbic acid, benzoic acid, and sulfur dioxide concentrations,[52] representing some of the commonly used food preservation methods. Methylene Blue is used to test for the presence of live yeast cells.	https://www.wikidoc.org/index.php/Yeast
368e15f3f7dffb1fca49a1f87a990b4f08a350ce	wikidoc	Ypadu	Ypadu # Ypadú Ypadú or ypadu is an unrefined, unconcentrated powder made from coca leaves and the ash of various other plants. Like coca teas consumed in Peru to adapt to sickness induced by high elevation, it has a long ethnobotanical history and cultural associations. A report by Pien Metaal and others written for the Transnational Institute ("?", p. 19) states that: "Ypadú would not be more than an element in Amazonian botanical and ethnographic folklore were it not for its use, which enshrines it as a precursor in the current trend in favour of the 'industrialisation' of coca. Because ypadú leaves are very fibrous and their alkaloid content is low, lowland cultures have developed a process for transformation of the leaf that produces a very fine powder . The traditional technique consists of toasting the leaves in an earthenware pot, crushing them in a wooden mortar, mixing them with ash from the leaf of the yarumo plant (Cecropia spp.), and passing them through a sieve to eliminate the fibrous part. The resulting powder is easily handled and rapidly absorbed. Experiments done by Anthony Henman in Lima and São Paulo have shown that a modern ypadú, made with any variety of coca leaf and with ash made from quinoa straw, is well accepted by people who find the laborious process of chewing whole leaves to be tedious. Ypadú could become the much-desired bridge between the traditional use of coca and new industrialised products demanded by the 21st-century world. Although it probably would not replace the traditional chewing of coca leaves, or chacchado, in the Andean countries, it could become and alternative to refined cocaine, which – despite all efforts to suppress it – has become a mass-consumption commodity in large areas of the world. As a result, it could become an effective tool for public policies that seek 'harm reduction' and a way to absorb the properties of coca. In short, ypadú would help achieve what no government has managed to do: re-educate the demand for cocaine and, along the way, return coca to its deserved pre-eminence as an ancestral plant of wisdom." ("Coca yes, cocaine no?", p. 19) # Contemporary development of an ancient tradition Foreign visitors to some Latin American countries have demonstrated an interest in commercial and cultural uses of the stimulant properties of the coca plant which are less harmful than cocaine, which is highly and unnaturally refined. ypadu. A few websites depict a mild modern preparation of the powdery ypadu mixture using plastic jars and coffee grinders or food processors rather than the traditional implements such as clay vessels and mortar-and-pestles fashioned from wood. Peruvian coca of the genus Erythroxilum coca var has reportedly been used in this adaptation to produce effective mixtures with pleasant taste. # Support for the use of Ypadu Protagonists of coca recommend mass production of ypadu as a harmless replacement for heavily refined and concentrated cocaine. They argue that a mild alternative to cocaine would cut into the illicit drug trade and the costs it imposes on societies. # Criticism Antagonists of Coca claim that mild coca derivatives can serve as gateways to cocaine abuse. The also claim that economic rewards brought to coca producers would fuel illicit coca production and in turn the cocaine cartels.	Ypadu # Ypadú Ypadú or ypadu is an unrefined, unconcentrated powder made from coca leaves and the ash of various other plants. Like coca teas consumed in Peru to adapt to sickness induced by high elevation, it has a long ethnobotanical history and cultural associations. A report by Pien Metaal and others written for the Transnational Institute ("[Coca yes, cocaine no]?", p. 19) states that: "Ypadú would not be more than an element in Amazonian botanical and ethnographic folklore were it not for its use, which enshrines it as a precursor in the current trend in favour of the 'industrialisation' of coca. Because ypadú leaves are very fibrous and their alkaloid content is low, lowland cultures have developed a process for transformation of the leaf that produces a very fine powder [...]. The traditional technique consists of toasting the leaves in an earthenware pot, crushing them in a wooden mortar, mixing them with ash from the leaf of the yarumo plant (Cecropia spp.), and passing them through a sieve to eliminate the fibrous part. The resulting powder is easily handled and rapidly absorbed. Experiments done by Anthony Henman in Lima and São Paulo have shown that a modern ypadú, made with any variety of coca leaf and with ash made from quinoa straw, is well accepted by people who find the laborious process of chewing whole leaves to be tedious. Ypadú could become the much-desired bridge between the traditional use of coca and new industrialised products demanded by the 21st-century world. Although it probably would not replace the traditional chewing of coca leaves, or chacchado, in the Andean countries, it could become and alternative to refined cocaine, which – despite all efforts to suppress it – has become a mass-consumption commodity in large areas of the world. As a result, it could become an effective tool for public policies that seek 'harm reduction' and a way to absorb the properties of coca. In short, ypadú would help achieve what no government has managed to do: re-educate the demand for cocaine and, along the way, return coca to its deserved pre-eminence as an ancestral plant of wisdom." ("Coca yes, cocaine no?", p. 19) # Contemporary development of an ancient tradition Foreign visitors to some Latin American countries have demonstrated an interest in commercial and cultural uses of the stimulant properties of the coca plant which are less harmful than cocaine, which is highly and unnaturally refined. ypadu. A few websites depict a mild modern preparation of the powdery ypadu mixture using plastic jars and coffee grinders or food processors rather than the traditional implements such as clay vessels and mortar-and-pestles fashioned from wood. Peruvian coca of the genus Erythroxilum coca var has reportedly been used in this adaptation to produce effective mixtures with pleasant taste. # Support for the use of Ypadu Protagonists of coca recommend mass production of ypadu as a harmless replacement for heavily refined and concentrated cocaine. They argue that a mild alternative to cocaine would cut into the illicit drug trade and the costs it imposes on societies. # Criticism Antagonists of Coca claim that mild coca derivatives can serve as gateways to cocaine abuse. The also claim that economic rewards brought to coca producers would fuel illicit coca production and in turn the cocaine cartels. # External links http://www.tni.org/reports/drugs/debate13.pdf (PDF) Template:WikiDoc Sources	https://www.wikidoc.org/index.php/Ypadu
daed5b04419db4c5477930b6e1a546b214ccd1f6	wikidoc	ZAP70	ZAP70 ZAP-70 (Zeta-chain-associated protein kinase 70) is a protein normally expressed near the surface membrane of T cells and natural killer cells. It is part of the T cell receptor, and plays a critical role in T-cell signaling. Its molecular weight is 70 kDa, and it is a member of the protein-tyrosine kinase family. # Clinical significance ZAP-70 in B cells is used as a prognostic marker in identifying different forms of chronic lymphocytic leukemia (CLL). DNA analysis has distinguished two major types of CLL, with different survival times. CLL that is positive for the marker ZAP-70 has an average survival of 8 years. CLL that is negative for ZAP-70 has an average survival of more than 25 years. Many patients, especially older ones, with slowly progressing disease can be reassured and may not need any treatment in their lifetimes. In systemic lupus erythematosus, the Zap-70 receptor pathway is missing and Syk takes its place. ZAP70 deficiency results in a form of immune deficiency. # Function T lymphocytes are activated by engagement of the T cell receptor with processed antigen fragments presented by professional antigen presenting cells (i.e. macrophages, dendritic cells and B cells) via the MHC. Upon this activation, the TCR co-receptor CD4 or CD8 binds to the MHC, activating the co-receptor associated tyrosine kinase Lck. Lck phosphorylates the intracellular portions of the CD3 complex (called ITAMs), creating a docking site for ZAP-70. The most important member of the CD3 family is CD3-zeta, to which ZAP-70 binds (hence the abbreviation). The tandem SH2-domains of ZAP-70 are engaged by the doubly phosphorylated ITAMs of CD3-zeta, which positions ZAP-70 to phosphorylate the transmembrane protein linker of activated T cells (LAT). Phosphorylated LAT, in turn, serves as a docking site to which a number of signalling proteins bind including SLP-76. SLP-76 is also phosphorylated by ZAP-70, which requires its activation by Src family kinases. The final outcome of T cell activation is the transcription of several gene products which allow the T cells to differentiate, proliferate and secrete a number of cytokines. # Interactions ZAP-70 has been shown to interact with: - Cbl gene, - Drebrin-like, - FYN, - Lck, - LAT, - SHB, and - SHC1.	ZAP70 ZAP-70 (Zeta-chain-associated protein kinase 70) is a protein normally expressed near the surface membrane of T cells and natural killer cells. It is part of the T cell receptor, and plays a critical role in T-cell signaling. Its molecular weight is 70 kDa, and it is a member of the protein-tyrosine kinase family. # Clinical significance ZAP-70 in B cells is used as a prognostic marker in identifying different forms of chronic lymphocytic leukemia (CLL). DNA analysis has distinguished two major types of CLL, with different survival times. CLL that is positive for the marker ZAP-70 has an average survival of 8 years. CLL that is negative for ZAP-70 has an average survival of more than 25 years. Many patients, especially older ones, with slowly progressing disease can be reassured and may not need any treatment in their lifetimes.[1] In systemic lupus erythematosus, the Zap-70 receptor pathway is missing and Syk takes its place.[2] ZAP70 deficiency results in a form of immune deficiency. # Function T lymphocytes are activated by engagement of the T cell receptor with processed antigen fragments presented by professional antigen presenting cells (i.e. macrophages, dendritic cells and B cells) via the MHC. Upon this activation, the TCR co-receptor CD4 or CD8 binds to the MHC, activating the co-receptor associated tyrosine kinase Lck. Lck phosphorylates the intracellular portions of the CD3 complex (called ITAMs), creating a docking site for ZAP-70. The most important member of the CD3 family is CD3-zeta, to which ZAP-70 binds (hence the abbreviation). The tandem SH2-domains of ZAP-70 are engaged by the doubly phosphorylated ITAMs of CD3-zeta, which positions ZAP-70 to phosphorylate the transmembrane protein linker of activated T cells (LAT). Phosphorylated LAT, in turn, serves as a docking site to which a number of signalling proteins bind including SLP-76. SLP-76 is also phosphorylated by ZAP-70, which requires its activation by Src family kinases.[3] The final outcome of T cell activation is the transcription of several gene products which allow the T cells to differentiate, proliferate and secrete a number of cytokines. # Interactions ZAP-70 has been shown to interact with: - Cbl gene,[4][5] - Drebrin-like,[6] - FYN,[7] - Lck,[8][9] - LAT,[10][11] - SHB,[12] and - SHC1.[13]	https://www.wikidoc.org/index.php/ZAP70
7b870cee2cecb2d32f3cb37a8c353009352dfbdb	wikidoc	ZFP36	ZFP36 Tristetraprolin (TTP), also known as zinc finger protein 36 homolog (ZFP36), is a protein that in humans, mice and rats is encoded by the ZFP36 gene. It is a member of the TIS11 (TPA-induced sequence) family, along with butyrate response factors 1 and 2. TTP binds to AU-rich elements (AREs) in the 3'-untranslated regions (UTRs) of the mRNAs of some cytokines and promotes their degradation. For example, TTP is a component of a negative feedback loop that interferes with TNF-alpha production by destabilizing its mRNA. Mice deficient in TTP develop a complex syndrome of inflammatory diseases. # Interactions ZFP36 has been shown to interact with 14-3-3 protein family members, such as YWHAH, and with NUP214, a member of the nuclear pore complex. # Regulation Post-transcriptionally, TTP is regulated in several ways. The subcellular localization of TTP is influenced by interactions with protein partners such as the 14-3-3 family of proteins. These interactions and, possibly, interactions with target mRNAs are affected by the phosphorylation state of TTP, as the protein can be posttranslationally modified by a large number of protein kinases. There is some evidence that the TTP transcript may also be targeted by microRNAs, such as miR-29a.	ZFP36 Tristetraprolin (TTP), also known as zinc finger protein 36 homolog (ZFP36), is a protein that in humans, mice and rats is encoded by the ZFP36 gene.[1][2] It is a member of the TIS11 (TPA-induced sequence) family, along with butyrate response factors 1 and 2.[3] TTP binds to AU-rich elements (AREs) in the 3'-untranslated regions (UTRs) of the mRNAs of some cytokines and promotes their degradation. For example, TTP is a component of a negative feedback loop that interferes with TNF-alpha production by destabilizing its mRNA.[4] Mice deficient in TTP develop a complex syndrome of inflammatory diseases.[4] # Interactions ZFP36 has been shown to interact with 14-3-3 protein family members, such as YWHAH,[5] and with NUP214, a member of the nuclear pore complex.[6] # Regulation Post-transcriptionally, TTP is regulated in several ways.[3] The subcellular localization of TTP is influenced by interactions with protein partners such as the 14-3-3 family of proteins. These interactions and, possibly, interactions with target mRNAs are affected by the phosphorylation state of TTP, as the protein can be posttranslationally modified by a large number of protein kinases.[3] There is some evidence that the TTP transcript may also be targeted by microRNAs, such as miR-29a.[3]	https://www.wikidoc.org/index.php/ZFP36
671788977a32682f7f0aaedc4a42148b46b08d6c	wikidoc	ZFP57	ZFP57 Zinc finger protein 57 homolog (ZFP57), also known as zinc finger protein 698 (ZNF698), is a protein that in humans is encoded by the ZFP57 gene. # Function The protein encoded by this gene is a zinc finger protein containing a KRAB domain. Studies in mouse suggest that this protein may function as a transcriptional repressor. # Clinical significance Mutations in the ZFP57 gene may be associated with transient neonatal diabetes mellitus.	ZFP57 Zinc finger protein 57 homolog (ZFP57), also known as zinc finger protein 698 (ZNF698), is a protein that in humans is encoded by the ZFP57 gene.[1] # Function The protein encoded by this gene is a zinc finger protein containing a KRAB domain. Studies in mouse suggest that this protein may function as a transcriptional repressor.[1] # Clinical significance Mutations in the ZFP57 gene may be associated with transient neonatal diabetes mellitus.[2]	https://www.wikidoc.org/index.php/ZFP57
46c0fb8906b34194cd07386f1040678452e06b4c	wikidoc	ZFPM2	ZFPM2 Zinc finger protein ZFPM2, i.e. zinc finger protein, FOG family member 2, but also termed Friend of GATA2, Friend of GATA-2, FOG2, or FOG-2, is a protein that in humans is encoded by the ZFPM2 and in mice by the Zfpm2 gene. The zinc finger-containing protein encoded by this gene is a widely expressed member of the FOG family of regulators of transcription factors. The family consists of the ZFPM1 and ZFPM2 genes in humans and Zfpm1 and Zfpm2 genes in mice. Its members may act as coactivators and/or corepressors to modulate the activity of GATA transcription factors. That is, the ZFPM2 protein appears able to interact directly with and thereby either enhance or repress the ability of GATA transcription factors to stimulate the expression of their target genes; the direction of ZFPM2's actions depends on the contexts of the promoter sections of the various GATA target genes. The ZFPM2 protein interacts primarily with the GATA4 but also with GATA2, GATA5, and GATA6 transcription factors. ZFPM2 protein's interaction with GATA4 is notable for controlling the embryonic development of various tissues, particularly the heart, diaphragm, and gonads. Correspondingly, ZFPM2 mutations are responsible for certain forms of congenital heart defects, congenital diaphragmatic hernias , and ambiguous genitalia in mice as well as humans. # Gene The ZFPM2 gene is found in a wide range of animal species from flies to humans. The human gene is located on the long or "q" arm of chromosome 8 at position 23.1 (i.e. 8q23.1) and consists of 9 exons. The equivalent mouse gene, Zfpm2, is located on chromosome 15 and consists of 8 exons. Knockout of ZFPM2 is embryonic lethal in mice, with mice dying at embryonic day 12.5-15.5 due to congenital cardiac defects (thin heart ventricular muscle, common atrioventricular canal, and the tetralogy of Fallot malformation. ZFPM2 expression in mice is also required for normal development of the gonads, lung and diaphragm. # Protein Both the human and mouse ZFPM2 proteins consists of 1151 amino acids and are expressed in various tissues. The human protein is expressed at relatively high levels in the adult ovary and uterine endometrium while the mouse protein is expressed at relatively high levels in the central nervous system cerebellum and, during the early stages of its development, the heart. Human ZFPM2 contains 8 zinc finger structural motifs and interacts directly with various members of the GATA transcription factor family to modify their ability to stimulate the expression of their target genes. For example, it has been shown to bind directly with the N-terminal zinc finger of the GATA4 transcription factor to inhibit its ability to stimulate the expression of a target gene in an in vitro model system. The extreme N terminal end of the ZFPM2 protein contains two domains, one of which interacts directly with the Mi-2/NuRD complex (i.e. nucleosome remodeling and histone deacetylase complex or NuRD complex) and other of which binds CTBP1 or CTBP2 proteins. The NuRD complex and the CtBPs are classified as corepressors. that act to promote the ability of ZFPM2 to inhibit the ability of GATA proteins to stimulate the expression of their target genes. # Pathophysiology ZFPM2 regulates the expression of certain GATA target genes by up-regulating or down-regulating the ability of the GATA transcription factors, primarily GATA3, GATA4, GATA5, and GATA6, to stimulate the expression of their target genes. Interactions with the NuRD complex or a CTBP can cause ZFPM2 to inhibit the ability of GATA3-6 proteins to stimulate the expression of their target genes. # Clinical relevancy ## Congenital heart disease Mutations in the ZFPM2 gene are responsible for rare and sporadic cases of congenital heart disease. These include cases of Tetralogy of Fallot, truncus arteriosus, failure to from the pulmonary artery valve combined with ventricular septal defect, double outlet right ventricle, transposition of the great arteries, and interrupted aortic arch. Sporadic cases of Tetralogy of Fallot were also found in cases where the levels of Hypermethylation at CpG sites in the ZFPM2 gene promotor were greatly elevated; these cases were associated with decreases cardiac tissue levels of mRNA for ZFPM2. These cases likely reflect the role of ZFPM2 in promoting GATA4's function in the embryonic development of the heart. ## Congenital diaphragmatic hernia ZFPM2 heterozygous gene mutations are responsible for sporadic cases of congenital diaphragmatic hernias. This development disorder may be the underlying cause for the development of congenital lung dysplasia and pulmonary vascular disorder that leads to pulmonary hypertension. These defects are considered due to haploinsufficiency in ZFPM2 protein and consequential failure of GATA4 to promote normal lung development. ## Sex development Heterozygous mutations in the ZFPM2 gene are responsible for sporadic, very rare cases of a familial form of disorders of sex development, ambiguous genitalia. The disorder likely reflects haploinsufficiency of the ZFPM2 protein and consequential reduced regulation of GATA4 in promoting normal development of the gonads.	ZFPM2 Zinc finger protein ZFPM2, i.e. zinc finger protein, FOG family member 2, but also termed Friend of GATA2, Friend of GATA-2, FOG2, or FOG-2, is a protein that in humans is encoded by the ZFPM2 and in mice by the Zfpm2 gene.[1][2][3] The zinc finger-containing protein encoded by this gene is a widely expressed member of the FOG family of regulators of transcription factors. The family consists of the ZFPM1 and ZFPM2 genes in humans and Zfpm1 and Zfpm2 genes in mice. Its members may act as coactivators and/or corepressors to modulate the activity of GATA transcription factors. That is, the ZFPM2 protein appears able to interact directly with and thereby either enhance or repress the ability of GATA transcription factors to stimulate the expression of their target genes; the direction of ZFPM2's actions depends on the contexts of the promoter sections of the various GATA target genes.[3] The ZFPM2 protein interacts primarily with the GATA4 but also with GATA2, GATA5, and GATA6 transcription factors. ZFPM2 protein's interaction with GATA4 is notable for controlling the embryonic development of various tissues, particularly the heart, diaphragm, and gonads. Correspondingly, ZFPM2 mutations are responsible for certain forms of congenital heart defects, congenital diaphragmatic hernias ,[4] and ambiguous genitalia[5] in mice as well as humans. # Gene The ZFPM2 gene is found in a wide range of animal species from flies to humans. The human gene is located on the long or "q" arm of chromosome 8 at position 23.1 (i.e. 8q23.1) and consists of 9 exons.[6] The equivalent mouse gene, Zfpm2, is located on chromosome 15 and consists of 8 exons.[7] Knockout of ZFPM2 is embryonic lethal in mice, with mice dying at embryonic day 12.5-15.5 due to congenital cardiac defects (thin heart ventricular muscle, common atrioventricular canal, and the tetralogy of Fallot malformation.[8] ZFPM2 expression in mice is also required for normal development of the gonads, lung and diaphragm.[9] # Protein Both the human and mouse ZFPM2 proteins consists of 1151 amino acids and are expressed in various tissues. The human protein is expressed at relatively high levels in the adult ovary and uterine endometrium while the mouse protein is expressed at relatively high levels in the central nervous system cerebellum and, during the early stages of its development, the heart. Human ZFPM2 contains 8 zinc finger structural motifs and interacts directly with various members of the GATA transcription factor family to modify their ability to stimulate the expression of their target genes. For example, it has been shown to bind directly with the N-terminal zinc finger of the GATA4 transcription factor to inhibit its ability to stimulate the expression of a target gene in an in vitro model system.[9][10][7][6] The extreme N terminal end of the ZFPM2 protein contains two domains, one of which interacts directly with the Mi-2/NuRD complex (i.e. nucleosome remodeling and histone deacetylase complex or NuRD complex) and other of which binds CTBP1 or CTBP2 proteins. The NuRD complex and the CtBPs are classified as corepressors. that act to promote the ability of ZFPM2 to inhibit the ability of GATA proteins to stimulate the expression of their target genes.[9] # Pathophysiology ZFPM2 regulates the expression of certain GATA target genes by up-regulating or down-regulating the ability of the GATA transcription factors, primarily GATA3, GATA4, GATA5, and GATA6, to stimulate the expression of their target genes. Interactions with the NuRD complex or a CTBP can cause ZFPM2 to inhibit the ability of GATA3-6 proteins to stimulate the expression of their target genes.[9] # Clinical relevancy ## Congenital heart disease Mutations in the ZFPM2 gene are responsible for rare and sporadic cases of congenital heart disease. These include cases of Tetralogy of Fallot, truncus arteriosus, failure to from the pulmonary artery valve combined with ventricular septal defect, double outlet right ventricle, transposition of the great arteries, and interrupted aortic arch.[10] Sporadic cases of Tetralogy of Fallot were also found in cases where the levels of Hypermethylation at CpG sites in the ZFPM2 gene promotor were greatly elevated; these cases were associated with decreases cardiac tissue levels of mRNA for ZFPM2.[11] These cases likely reflect the role of ZFPM2 in promoting GATA4's function in the embryonic development of the heart.[8][9] ## Congenital diaphragmatic hernia ZFPM2 heterozygous gene mutations are responsible for sporadic cases of congenital diaphragmatic hernias. This development disorder may be the underlying cause for the development of congenital lung dysplasia and pulmonary vascular disorder that leads to pulmonary hypertension. These defects are considered due to haploinsufficiency in ZFPM2 protein and consequential failure of GATA4 to promote normal lung development.[4][12] ## Sex development Heterozygous mutations in the ZFPM2 gene are responsible for sporadic, very rare cases of a familial form of disorders of sex development, ambiguous genitalia. The disorder likely reflects haploinsufficiency of the ZFPM2 protein and consequential reduced regulation of GATA4 in promoting normal development of the gonads.[5]	https://www.wikidoc.org/index.php/ZFPM2
a1704226c2658fef047775d590beeeb20438f81b	wikidoc	ZGRF1	ZGRF1 ZGRF1 is a protein in humans that is encoded by the ZGRF1 gene that has uncharacterised function and a weight of 236.6 kDa. This gene shows relatively low expression in most human tissues, with increased expression in situations of chemical dependence. ZGRF1 is orthologous to nearly all kingdoms of Eukarya. Functional domains of this protein link it to a series of helicases, most notably the AAA_12 and AAA_11 domains. # Gene The entire gene is 97,663 base pairs long and has an unprocessed mRNA that is 6,740 nucleotides in length. It consists of 28 exons that encode for a 2104 amino acid protein. 12 splice variants exist for C4orf21. ## Locus ZGRF1 is located on the fourth chromosome on the 4q25 position near the LARP7 gene. It is encoded for on the minus strand. # Homology and evolution ## Homologous domains ZGRF1 contains a DUF2439 domain (domain of unknown function), zf-GRF domain, and AAA_11 and an AAA_12 domain (ATPases associated with diverse cellular activities). DUF domains are involved in telomere maintenance and meiotic segregation. AAA_11 and AAA_12 contain a P-loop motif which are involved in conjugative transfer proteins. Other helicase domains are also present in c4orf21 orthologs. ## Paralogs There are 9 moderately-related proteins in humans that are paralogous to the ATP-dependent helicase containing domains in the C-terminus of c4orf21 after the 1612th amino acid. A majority of these proteins are in the RNA helicase family. There are no known paralogs to the large N-terminal portion of the protein. ## Orthologs Complete orthologs of the c4orf21 gene are found in mammalia. The helicase domain containing C-terminus portion of the gene is conserved across Eukarya. # Protein ## Primary sequence ZGRF1 is 236.6 kDa. ## Post-translational modifications ZGRF1 has experimentally determined phosphorylation sites at the Y38, S137, S140, S325, and S864 positions. ## Secondary structure A weak transmembrane domain is predicted in the TMHMM server with one loop in the C-terminus of the protein prior to the helicase core. This domain contains both ends outside of a membrane. ## Tertiary domains and quaternary structure ZGRF1 has related structures to Upf1, a paralog. These structures have the capability to bind zinc ions and mRNA. # Function and biochemistry The function of ZGRF1 is unknown. Given this, the paralogs to the helicase core of the gene are associated with translation, transcription, nonsense-mediated mRNA decay, RNA decay, miRNA processing, RISC assembly, and pre-mRNA splicing. These paralogs operate under a SPF1 RNA helicase motif. Mov10, a paralog, and probable RNA helicase is required for RNA-mediated gene silencing by the RNA-induced silencing complex (RISC). It is also required for both miRNA-mediated translational repression and miRNA-mediated cleavage of complementary mRNAs by RISC, and for RNA-directed transcription and replication of the human hepatitis delta virus (HDV). Mov10 nteracts with small capped HDV RNAs derived from genomic hairpin structures that mark the initiation sites of RNA-dependent HDV RNA transcription. # Expression Expression is relatively low for c4orf21 compared to other proteins. Expression of c4orf21 is slightly elevated compared to its average expression in tissue in the hematopoietic and lymphatic systems, and is above average in the brain also. Lower averages exist in liver, pharynx, and skin tissue. ## Transcription factor interactions The transcriptional start site for ZGRF1 aligns best with ATF, CREB, deltaCREB, E2F, and E2F-1 transcription factor binding sites. # Interacting proteins C4orf21 shows predicted protein interaction with its AQR, DNA2, IGHMBP2, LOC91431, and SETX paralogs. # Clinical significance Upon examination of variable GEO profiles, there were many related to Hepatitis and other disorders of the liver. The best correlative studies were those in relation to liver transplant failure. ZGRF1 showed significantly increased expression in those who were nicotine dependent versus a control group of non-smokers. A paralog of ZGRF1 was found to inhibit HIV-1 Replication at multiple stages. Mov10 is involved in the biological processes of RNA-mediated gene silencing, transcription, transcription regulation and has hydrolase and helicase activity through ATP and RNA binding.	ZGRF1 ZGRF1 is a protein in humans that is encoded by the ZGRF1 gene that has uncharacterised function and a weight of 236.6 kDa.[1] This gene shows relatively low expression in most human tissues, with increased expression in situations of chemical dependence. ZGRF1 is orthologous to nearly all kingdoms of Eukarya. Functional domains of this protein link it to a series of helicases, most notably the AAA_12 and AAA_11 domains. # Gene The entire gene is 97,663 base pairs long and has an unprocessed mRNA that is 6,740 nucleotides in length. It consists of 28 exons that encode for a 2104 amino acid protein. 12 splice variants exist for C4orf21. ## Locus ZGRF1 is located on the fourth chromosome on the 4q25 position near the LARP7 gene. It is encoded for on the minus strand. # Homology and evolution ## Homologous domains ZGRF1 contains a DUF2439 domain (domain of unknown function), zf-GRF domain, and AAA_11 and an AAA_12 domain (ATPases associated with diverse cellular activities). DUF domains are involved in telomere maintenance and meiotic segregation. AAA_11 and AAA_12 contain a P-loop motif which are involved in conjugative transfer proteins. Other helicase domains are also present in c4orf21 orthologs. ## Paralogs There are 9 moderately-related proteins in humans that are paralogous to the ATP-dependent helicase containing domains in the C-terminus of c4orf21 after the 1612th amino acid. A majority of these proteins are in the RNA helicase family. There are no known paralogs to the large N-terminal portion of the protein. ## Orthologs Complete orthologs of the c4orf21 gene are found in mammalia. The helicase domain containing C-terminus portion of the gene is conserved across Eukarya. # Protein ## Primary sequence ZGRF1 is 236.6 kDa. ## Post-translational modifications ZGRF1 has experimentally determined phosphorylation sites at the Y38, S137, S140, S325, and S864 positions. ## Secondary structure A weak transmembrane domain is predicted in the TMHMM server with one loop in the C-terminus of the protein prior to the helicase core. This domain contains both ends outside of a membrane. ## Tertiary domains and quaternary structure ZGRF1 has related structures to Upf1, a paralog. These structures have the capability to bind zinc ions and mRNA. # Function and biochemistry The function of ZGRF1 is unknown. Given this, the paralogs to the helicase core of the gene are associated with translation, transcription, nonsense-mediated mRNA decay, RNA decay, miRNA processing, RISC assembly, and pre-mRNA splicing.[2] These paralogs operate under a SPF1 RNA helicase motif.[3] Mov10, a paralog, and probable RNA helicase is required for RNA-mediated gene silencing by the RNA-induced silencing complex (RISC). It is also required for both miRNA-mediated translational repression and miRNA-mediated cleavage of complementary mRNAs by RISC, and for RNA-directed transcription and replication of the human hepatitis delta virus (HDV). Mov10 nteracts with small capped HDV RNAs derived from genomic hairpin structures that mark the initiation sites of RNA-dependent HDV RNA transcription. # Expression Expression is relatively low for c4orf21 compared to other proteins. Expression of c4orf21 is slightly elevated compared to its average expression in tissue in the hematopoietic and lymphatic systems, and is above average in the brain also. Lower averages exist in liver, pharynx, and skin tissue.[4] ## Transcription factor interactions The transcriptional start site for ZGRF1 aligns best with ATF, CREB, deltaCREB, E2F, and E2F-1 transcription factor binding sites. # Interacting proteins C4orf21 shows predicted protein interaction with its AQR, DNA2, IGHMBP2, LOC91431, and SETX paralogs.[5] # Clinical significance Upon examination of variable GEO profiles, there were many related to Hepatitis and other disorders of the liver. The best correlative studies were those in relation to liver transplant failure.[6][7] ZGRF1 showed significantly increased expression in those who were nicotine dependent versus a control group of non-smokers.[7][8] A paralog of ZGRF1 was found to inhibit HIV-1 Replication at multiple stages. Mov10 is involved in the biological processes of RNA-mediated gene silencing, transcription, transcription regulation and has hydrolase and helicase activity through ATP and RNA binding.[9]	https://www.wikidoc.org/index.php/ZGRF1
660cb6f5ba077920fe08f60a82ad66785955a896	wikidoc	Zocor	Zocor Synonyms / Brand Names:Cholestat, Coledis, Colemin, Corolin, Denan, Labistatin, Lipex, Lodales, Medipo, Nivelipol, Pantok, Rendapid, Simovil, Simvastatin, Simvastatina, Simvastatine, Simvastatinum, Sinvacor, Sivastin, Synvinolin, Vasotenal, Vytorin, Zocor, Zocord # Dosing and Administration The recommended usual starting dose is 20 to 40 mg once a day in the evening. For patients at high risk for a CHD event due to existing coronary heart disease, diabetes, peripheral vessel disease, history -f stroke or other cerebrovascular disease, the recommended starting dose is 40 mg/day. Lipid determinations should be performed after 4 weeks of therapy and periodically thereafter For more information on dosing please refer to Zocor instructions for administration FDA Package Insert Resources Indications, Contraindications, Side Effects, Drug Interactions, etc. Calculate Creatine Clearance On line calculator of your patients Cr Cl by a variety of formulas. Convert pounds to Kilograms On line calculator of your patients weight in pounds to Kg for dosing estimates. Publication Resources Recent articles, WikiDoc State of the Art Review, Textbook Information Trial Resources Ongoing Trials, Trial Results Guidelines & Evidence Based Medicine Resources US National Guidelines, Cochrane Collaboration, etc. Media Resources Slides, Video, Images, MP3, Podcasts, etc. Patient Resources Discussion Groups, Handouts, Blogs, News, etc. International Resources en Español # FDA Package Insert Resources Indications Contraindications Side Effects Drug Interactions Precautions Overdose Instructions for Administration How Supplied Pharmacokinetics and Molecular Data FDA label FDA on Zocor Return to top # Publication Resources Most Recent Articles on Zocor Review Articles on Zocor Articles on Zocor in N Eng J Med, Lancet, BMJ WikiDoc State of the Art Review Textbook Information on Zocor Return to top # Trial Resources Ongoing Trials with Zocor at Clinical Trials.gov Trial Results with Zocor Return to top # Guidelines & Evidence Based Medicine Resources US National Guidelines Clearinghouse on Zocor Cochrane Collaboration on Zocor Cost Effectiveness of Zocor Return to top # Media Resources Powerpoint Slides on Zocor Images of Zocor Podcasts & MP3s on Zocor Videos on Zocor Return to top # Patient Resources Patient Information from National Library of Medicine Patient Resources on Zocor Discussion Groups on Zocor Patient Handouts on Zocor Blogs on Zocor Zocor in the News Zocor in the Marketplace Return to top # International Resources Zocor en Español Return to top Adapted from the FDA Package Insert.	Zocor Synonyms / Brand Names:Cholestat, Coledis, Colemin, Corolin, Denan, Labistatin, Lipex, Lodales, Medipo, Nivelipol, Pantok, Rendapid, Simovil, Simvastatin, Simvastatina, Simvastatine, Simvastatinum, Sinvacor, Sivastin, Synvinolin, Vasotenal, Vytorin, Zocor, Zocord Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] # Dosing and Administration The recommended usual starting dose is 20 to 40 mg once a day in the evening. For patients at high risk for a CHD event due to existing coronary heart disease, diabetes, peripheral vessel disease, history of stroke or other cerebrovascular disease, the recommended starting dose is 40 mg/day. Lipid determinations should be performed after 4 weeks of therapy and periodically thereafter For more information on dosing please refer to Zocor instructions for administration FDA Package Insert Resources Indications, Contraindications, Side Effects, Drug Interactions, etc. Calculate Creatine Clearance On line calculator of your patients Cr Cl by a variety of formulas. Convert pounds to Kilograms On line calculator of your patients weight in pounds to Kg for dosing estimates. Publication Resources Recent articles, WikiDoc State of the Art Review, Textbook Information Trial Resources Ongoing Trials, Trial Results Guidelines & Evidence Based Medicine Resources US National Guidelines, Cochrane Collaboration, etc. Media Resources Slides, Video, Images, MP3, Podcasts, etc. Patient Resources Discussion Groups, Handouts, Blogs, News, etc. International Resources en Español # FDA Package Insert Resources Indications Contraindications Side Effects Drug Interactions Precautions Overdose Instructions for Administration How Supplied Pharmacokinetics and Molecular Data FDA label FDA on Zocor Return to top # Publication Resources Most Recent Articles on Zocor Review Articles on Zocor Articles on Zocor in N Eng J Med, Lancet, BMJ WikiDoc State of the Art Review Textbook Information on Zocor Return to top # Trial Resources Ongoing Trials with Zocor at Clinical Trials.gov Trial Results with Zocor Return to top # Guidelines & Evidence Based Medicine Resources US National Guidelines Clearinghouse on Zocor Cochrane Collaboration on Zocor Cost Effectiveness of Zocor Return to top # Media Resources Powerpoint Slides on Zocor Images of Zocor Podcasts & MP3s on Zocor Videos on Zocor Return to top # Patient Resources Patient Information from National Library of Medicine Patient Resources on Zocor Discussion Groups on Zocor Patient Handouts on Zocor Blogs on Zocor Zocor in the News Zocor in the Marketplace Return to top # International Resources Zocor en Español Return to top Adapted from the FDA Package Insert.	https://www.wikidoc.org/index.php/Zocor
7121069789a734392179549753fa80343fc9c318	wikidoc	2C-B	2C-B 2C-B, or 4-bromo-2,5-dimethoxyphenethylamine (sometimes referred to as 4-Bromo-2,5-dimethoxybenzeneethanamine) is a psychedelic drug of the 2C family, an entactogen. It was first synthesized by Alexander Shulgin in 1974. In his book PIHKAL (Phenethylamines I Have Known and Loved), the dosage range is listed as 16–24 mg. 2C-B is sold as a white powder sometimes pressed in tablets or gel caps. The drug is usually taken orally, but sometimes is insufflated. # Origins and history 2C-B was synthesized from 2,5-dimethoxybenzaldehyde by Alexander Shulgin in 1974. It first saw use among the psychiatric community as an aid during therapy. It was considered one of the best drugs for this purpose because of its short duration, relative absence of side effects, and comparably mild nature. Shortly after becoming popular in the medical community, it became popular recreationally. 2C-B was first sold commercially as an aphrodisiac under the tradename "Eros" which was manufactured by the German phamaceutical company Drittewelle. Recently 2C-B has been distributed under the street name "Nexus". Other street names include "Venus", "Bees", and "bromo-mescaline" though this name is incorrect as it does not contain any mescaline. Internationally, 2C-B is a Schedule II drug under the Convention on Psychotropic Substances. In the United States, a notice of proposed rulemaking published on December 20, 1994 in the Federal Register (59 FR 65521) and after a review of relevant data, the Deputy Administrator of the Drug Enforcement Administration (DEA) proposed to place 4-bromo-2,5-DMPEA into Schedule I, making 2C-B illegal in the United States. This became permanent law July 2, 1995. # Toxicity and dosage The September 1998 Journal of Analytical Toxicology reported that very little data exists about the pharmacological properties, metabolism, and toxicity of 2C-B. The relationship between its use and disease and death are unknown. At oral doses around 5–15 mg, 2C-B produces an entactogenic effect. But common recreational doses range from 15–40 mg, at which intense visual and auditory effects are experienced. The intensity of the effects increases with dosage. While considered foolhardy, people have survived doses as high as 200mg without negative effects. However, doses that high often lead to blackouts and erratic behavior. # Effects Effects of 2C-B include.: - Users describe effects as a mix between LSD and MDMA, although unlike a combination of the two. 2C-B is reportedly less dissociative and controlling than LSD, and less directive and speedy than MDMA. The drug has a stimulant effect and positive mood shift, both of which are mild compared to LSD or MDMA. - Some users report aphrodisiac effects at lower doses (5-10mg). - At higher dosages (greater than 15mg) some users consider the hallucinations a "turn-off" or distracting. - The hallucinations have a tendency to decrease and then increase in intensity, giving the users a sense of "waves", and are popularly described as "clichéd 70's visuals". - Excessive giggling or smiling is common, as is a tendency for deeper "belly laughs". - Some users experience a decrease in visual acuity, paradoxically, others report sharper vision. - At low doses the experience may shift in intensity from engaging to mild/undetectable. Experienced users report the ability to take control of the effects and switch from engaged to sober at will. - Increased awareness of ones body; Attention may be brought to perceived 'imperfections' or internal body processes. - Possible side effects include: mild diarrhea, gas, and nausea. However, these effects are rare and the drug is generally easier on the body than MDMA (Ecstasy). - Many users report a lack of "comedown" or "crash," instead noting a gradual return to sobriety. However, there are reports of hangover effects, especially when combined with alcohol. The following effects are highly dose-dependent. - Open Eye Visuals (OEVs), such as cartoon-like distortions and red or green halos around objects are common. Closed Eye Visuals (CEVs) are more common than OEVs. - Affects and alters ability to communicate, engage in deep thought, or maintain attention span. - Some users report experiencing frightening or fearful effects during the experience. Users describe feeling frigid or cold on reaching a plateau, while others feel wrapped in comfortable blankets/ultimate pleasure. - Coordination may be affected, some users lose balance or have perceptual distinction problems. - Effects last roughly 4-8 hours. ## Dosage	2C-B Template:OrganicBox small 2C-B, or 4-bromo-2,5-dimethoxyphenethylamine (sometimes referred to as 4-Bromo-2,5-dimethoxybenzeneethanamine) is a psychedelic drug of the 2C family, an entactogen. It was first synthesized by Alexander Shulgin in 1974. In his book PIHKAL (Phenethylamines I Have Known and Loved), the dosage range is listed as 16–24 mg. 2C-B is sold as a white powder sometimes pressed in tablets or gel caps. The drug is usually taken orally, but sometimes is insufflated. # Origins and history 2C-B was synthesized from 2,5-dimethoxybenzaldehyde by Alexander Shulgin in 1974. It first saw use among the psychiatric community as an aid during therapy. It was considered one of the best drugs for this purpose because of its short duration, relative absence of side effects, and comparably mild nature. Shortly after becoming popular in the medical community, it became popular recreationally. 2C-B was first sold commercially as an aphrodisiac under the tradename "Eros" which was manufactured by the German phamaceutical company Drittewelle. Recently 2C-B has been distributed under the street name "Nexus". Other street names include "Venus", "Bees", and "bromo-mescaline" though this name is incorrect as it does not contain any mescaline. Internationally, 2C-B is a Schedule II drug under the Convention on Psychotropic Substances[1]. In the United States, a notice of proposed rulemaking published on December 20, 1994 in the Federal Register (59 FR 65521) and after a review of relevant data, the Deputy Administrator of the Drug Enforcement Administration (DEA) proposed to place 4-bromo-2,5-DMPEA into Schedule I, making 2C-B illegal in the United States. This became permanent law July 2, 1995. # Toxicity and dosage The September 1998 Journal of Analytical Toxicology reported that very little data exists about the pharmacological properties, metabolism, and toxicity of 2C-B. The relationship between its use and disease and death are unknown.[2] At oral doses around 5–15 mg, 2C-B produces an entactogenic effect. But common recreational doses range from 15–40 mg, at which intense visual and auditory effects are experienced. The intensity of the effects increases with dosage[3]. While considered foolhardy, people have survived doses as high as 200mg without negative effects.[citation needed] However, doses that high often lead to blackouts and erratic behavior.[citation needed] # Effects Effects of 2C-B include[4].: - Users describe effects as a mix between LSD and MDMA, although unlike a combination of the two. 2C-B is reportedly less dissociative and controlling than LSD, and less directive and speedy than MDMA. The drug has a stimulant effect and positive mood shift, both of which are mild compared to LSD or MDMA. - Some users report aphrodisiac effects at lower doses (5-10mg). - At higher dosages (greater than 15mg) some users consider the hallucinations a "turn-off" or distracting. - The hallucinations have a tendency to decrease and then increase in intensity, giving the users a sense of "waves", and are popularly described as "clichéd 70's visuals". - Excessive giggling or smiling is common, as is a tendency for deeper "belly laughs". - Some users experience a decrease in visual acuity, paradoxically, others report sharper vision. - At low doses the experience may shift in intensity from engaging to mild/undetectable. Experienced users report the ability to take control of the effects and switch from engaged to sober at will. - Increased awareness of ones body; Attention may be brought to perceived 'imperfections' or internal body processes. - Possible side effects include: mild diarrhea, gas, and nausea. However, these effects are rare and the drug is generally easier on the body than MDMA (Ecstasy). - Many users report a lack of "comedown" or "crash," instead noting a gradual return to sobriety. However, there are reports of hangover effects, especially when combined with alcohol. The following effects are highly dose-dependent. - Open Eye Visuals (OEVs), such as cartoon-like distortions and red or green halos around objects are common. Closed Eye Visuals (CEVs) are more common than OEVs. - Affects and alters ability to communicate, engage in deep thought, or maintain attention span. - Some users report experiencing frightening or fearful effects during the experience. Users describe feeling frigid or cold on reaching a plateau, while others feel wrapped in comfortable blankets/ultimate pleasure. - Coordination may be affected, some users lose balance or have perceptual distinction problems. - Effects last roughly 4-8 hours. ## Dosage	https://www.wikidoc.org/index.php/2C-B
f3c675af082b543dc79adad5910456df28a2992c	wikidoc	2C-C	2C-C 2C-C is a psychedelic drug of the 2C family. It was first synthesized by Alexander Shulgin, sometimes used as an entheogen. The full name of the chemical is 4-chloro-2,5-dimethoxyphenethylamine. In his book PIHKAL (Phenethylamines I Have Known and Loved), Shulgin lists the dosage range as 20 to 40 mg. 2C-C is usually taken orally, but may also be insufflated . 2C-C is unscheduled and uncontrolled in the United States, but possession and sales of 2C-C could potentially be prosecuted under the Federal Analog Act because of 2C-C's close structural similarity to 2C-B. Not much information is known about the toxicity of 2C-C. Many users report that 2C-C is gentler and more sedating than other closely related psychedelic phenethylamines. # Effects - The visual effects of 2C-C are similar to those of LSD or psilocybin mushrooms. Nasal insufflation or rectal administration bypasses first pass metabolism, requiring about half the dose normally used orally; the effects occur within 2-30 minutes via these routes and tend to last about an hour less. There are very few negative side effects attributed to 2C-C. - The effects can take up to two hours to manifest. - Over the approximate dose range 20-40mg, effects last respectively, approximately, 4 to 8 hours. Increased dosages increase the duration of the trip . # Reference - ↑ Template:CitePiHKAL - ↑ Template:CitePiHKAL	2C-C 2C-C is a psychedelic drug of the 2C family. It was first synthesized by Alexander Shulgin, sometimes used as an entheogen. The full name of the chemical is 4-chloro-2,5-dimethoxyphenethylamine. In his book PIHKAL (Phenethylamines I Have Known and Loved), Shulgin lists the dosage range as 20 to 40 mg. 2C-C is usually taken orally, but may also be insufflated [1]. 2C-C is unscheduled and uncontrolled in the United States, but possession and sales of 2C-C could potentially be prosecuted under the Federal Analog Act because of 2C-C's close structural similarity to 2C-B. Not much information is known about the toxicity of 2C-C. Many users report that 2C-C is gentler and more sedating than other closely related psychedelic phenethylamines. # Effects - The visual effects of 2C-C are similar to those of LSD or psilocybin mushrooms. Nasal insufflation or rectal administration bypasses first pass metabolism, requiring about half the dose normally used orally; the effects occur within 2-30 minutes via these routes and tend to last about an hour less. There are very few negative side effects attributed to 2C-C. - The effects can take up to two hours to manifest. - Over the approximate dose range 20-40mg, effects last respectively, approximately, 4 to 8 hours. Increased dosages increase the duration of the trip [2]. # Reference - ↑ Template:CitePiHKAL - ↑ Template:CitePiHKAL	https://www.wikidoc.org/index.php/2C-C
ec0d3eb666e89ab3ea40aef1cce67aee5513b1aa	wikidoc	2C-D	2C-D 2C-D is a psychedelic drug of the 2C family. It was first synthesized by Alexander Shulgin, sometimes used as an entheogen. The full name of the chemical is 2,5-dimethoxy-4-methyl-phenethylamine. In his book PiHKAL (Phenethylamines I Have Known and Loved), Shulgin lists the dosage range as being from 20 to 80 mg. Lower doses (generally 10mg or less) of 2C-D have been explored as a potential nootropic, albeit with mixed results. 2C-D is generally taken orally, though may be insufflated (ie taken nasally). Insufflating tends to cause intense pain, however, and the dosage level is usual much lower, typically in the region of 1 to 15mg. Not much information is known about the toxicity of 2C-D, as no major studies have been conducted. According to Shulgin, the effects of 2C-D typically last for 4-6 hours. Shulgin himself referred to this substance as a “pharmacological tofu,” meaning that when mixed with other substances, it can extend or potentiate their effects without coloring the experience too much, in a manner similar to how tofu absorbs the flavors of sauces or spices it is cooked with. Some people have claimed 2C-D is relatively uninteresting on its own, but many other users have strongly disagreed with this assessment and believe instead 2C-D to be a true psychedelic in its own right. Hanscarl Leuner, working in Germany, explored the use of 2C-D under the name LE-25 in psychotherapeutic research. # Law 2C-D is currently unscheduled and uncontrolled in the United States, but the possession and sale of 2C-D could potentially be prosecuted under the Federal Analog Act due to its structural similarities to 2C-B and 2C-T-7. 2C-D and all other compounds featuring in PiHKAL are illegal drugs in the United Kingdom.	2C-D 2C-D is a psychedelic drug of the 2C family. It was first synthesized by Alexander Shulgin, sometimes used as an entheogen. The full name of the chemical is 2,5-dimethoxy-4-methyl-phenethylamine. In his book PiHKAL (Phenethylamines I Have Known and Loved), Shulgin lists the dosage range as being from 20 to 80 mg. Lower doses (generally 10mg or less) of 2C-D have been explored as a potential nootropic, albeit with mixed results. 2C-D is generally taken orally, though may be insufflated (ie taken nasally). Insufflating tends to cause intense pain, however, and the dosage level is usual much lower, typically in the region of 1 to 15mg. Not much information is known about the toxicity of 2C-D, as no major studies have been conducted. According to Shulgin, the effects of 2C-D typically last for 4-6 hours. Shulgin himself referred to this substance as a “pharmacological tofu,” meaning that when mixed with other substances, it can extend or potentiate their effects without coloring the experience too much, in a manner similar to how tofu absorbs the flavors of sauces or spices it is cooked with. Some people have claimed 2C-D is relatively uninteresting on its own, but many other users have strongly disagreed with this assessment and believe instead 2C-D to be a true psychedelic in its own right. Hanscarl Leuner, working in Germany, explored the use of 2C-D under the name LE-25 in psychotherapeutic research. # Law 2C-D is currently unscheduled and uncontrolled in the United States, but the possession and sale of 2C-D could potentially be prosecuted under the Federal Analog Act due to its structural similarities to 2C-B and 2C-T-7. 2C-D and all other compounds featuring in PiHKAL are illegal drugs in the United Kingdom. # External links - 2C-D Entry in PIHKAL - Erowid 2C-D Vault # Categorization Template:Hallucinogenic phenethylamines Template:PiHKAL nl:2C-D Template:WikiDoc Sources	https://www.wikidoc.org/index.php/2C-D
6206fd9eff372e0f13951031a821a31a3f969b26	wikidoc	2C-E	2C-E 2C-E (2,5-dimethoxy-4-ethylphenethylamine) is a psychedelic drug and phenethylamine of the 2C family. It was first synthesized by Alexander Shulgin, sometimes used as an entheogen. It is commonly active in the 10-20 mg range, taken orally, and highly dose-sensitive. Insufflating (ie administering the chemical nasally) requires a much lower dose, typically not exceeding 5mgs, for noticeable effects, but tends to cause intense pain. Shulgin classified 2C-E as a member of the "magical half-dozen" in his book PiHKAL. Many have reported that the general effects of 2C-E are similar to those of the other psychedelic phenethylamines, but far more intense. Vivid hallucinations similar to those experienced while under the influence of LSD are common, and many reports would indicate that the effects of this particular chemical may be overly intense for those not well experienced with psychedelics . However, for those who are familiar with the compound, oral doses of 30+ mg are not uncommon and often produce no additional side effects than those described by users of lower doses. # Properties 2,5-dimethoxy-4-ethylphenethylamine is a colorless oil. Crystalline forms are obtained as the amine salt by reacting the free base with a mineral acid, typically HCl. Shulgin does not report an exact boiling point for the free base, stating only that during one synthesis the fraction boiling between 90-100C at 0.25 mm/Hg pressure was collected and converted to the hydrochloride salt. Shulgin also does not report a melting point for the hydrochloride salt. The melting point of 184-185C previously reported in this article is incorrect. The 184-185C melt point value refers to the melting point of the hydrochloride salt of 5-ethoxy-4-ethyl-2-methoxyphenethylamine (2CE-5ETO in Shulgin's nomenclature). The Material Safety Data Sheet for a commercial sample of 2,5-dimethoxy-4-ethylphenethylamine hydrochloride reported the melting point as 247-249C. In the absence of a published melting point for a verified sample, the melting point is currently reported in this article as unknown. # Effects The total duration of 2C-E's effects is generally between six and ten hours for an average dose, with the plateau lasting between three and six hours. For such a dose, the onset of effects takes approximately twenty to ninety minutes and perception may be somewhat altered for up to a day after ingestion. In extreme cases where between seventy-five and one hundred milligrams of 2C-E were ingested, the duration of effects has exceeded twenty-four hours, with plateaus exceeding ten hours in length and an onset of effects within the first five minutes after the ingestion of the drug. A few users of very high doses have reported "never feeling the same again" after having used this drug. The concurrent use of SSRIs generally has a palliative effect upon both the intensity and duration of the effects of 2C-E during their plateau stage. As compared to similar compounds such as 2C-I and 2C-B, 2C-E is more likely to produce strong synaesthesia, sound distortion and an enhancement of the experience of music, and, most notably, visuals. Some users have also reported having mystical and "ego death" experiences while under the influence of 2C-E. While many users of lower doses of 2C-E have reported that it produces mainly closed-eye visuals, users of higher doses have compared its open-eye visuals with those produced by LSD; a significant proportion of these comparisons have favored the visual effects of 2C-E in terms both of their geometric complexity and in the variety of colors seen during an experience. The euphoriant effect shared by several other psychedelic phenethylamines seems only to have been reported relatively rarely by users of 2C-E; it has been described it as "difficult" by people who use it, including its inventor, Shulgin: At doses approximating or exceeding twenty to twenty-five milligrams, 2C-E can produce intensely colorful, highly complex, moving, fractal-like patterning, persian carpet-type visuals, three-dimensional visual effects, and, sometimes, visual patterning strongly resembling biological structures, such as vines, tentacles, and even eyeballs. The visual distortions produced by 2C-E are comparable in some respects to those produced by mescaline, and some users of both drugs have reported that the visual effects of 2C-E are more emphatic of color than are mescaline's corresponding effects, while mescaline's visuals are more emphatic of geometric structure. 2C-E's body load is a highly unusual one. Several users have described it, roughly, as a "profound feeling of general discomfort". It is sometimes characterized by urges to shift the position of one's body, strong nausea at high doses leading often to vomiting, itching, prolonged tensing of unusual combinations of muscle groups which can occur without the user's knowledge over a long period of time, diarrhoea, and an accompanying feeling of "disconnection from one's digestive tract". Some users report little or no body load on 2C-E, and describe in its stead strong euphoria; one user on Erowid reported that it produced a stronger euphoria than did cocaine, although this is extremely rare among 2C-E users. A negative body load is much more common than positive effects in this area. 2C-E's distortion of sounds is also quite profound, and includes the flanging of sounds, echoing, pitch shifting, and the perceived synthesis of new sounds not derived from one's immediate environment, such as scraping, drilling, and popping. Again, many of the more unusual distortions of sound are only experienced after the ingestion (or, rarely, insufflation) of a higher dose. 2C-E can also produce distortions in the user's perception of the passage of time leading to an illusion of moderate to extreme time dilation. Like all psychedelics, 2C-E produces a very altered state of consciousness; one unusual side of 2C-E's effects is that some users have reported experiencing "relatively normal thought processes" even while experiencing visual and auditory distortions. These users suggest, in other words, that 2C-E doesn't impair judgment as deeply as do many other psychedelics with otherwise-similar effects; however, these claims have not been tested in any controlled study. The wide difference between different users' accounts of the intensity, duration, and nature of the effects of 2C-E can largely be accounted for by users' highly varying dosage of the drug. Sites like erowid suggest that an average dose of 2C-E might be between ten and fifteen milligrams, and gives the highest "heavy" dose as twenty-five milligrams. Elsewhere on the Internet, and especially in various forums for users of psychedelics, users have reported taking up to between seventy-five and one hundred milligrams of 2C-E, and the ensuing experiences have invariably been extremely intense and very long (in some cases upwards of twenty-four hours in duration). There have been no reported deaths from 2C-E use, so even these doses can be considered relatively safe considering how little is known about the long-term effects of the use of this substance. However, no experienced user of 2C-E has recommended doses this large for any newcomer; an appropriate starting dose might be between seven and twenty milligrams for someone intending to consume 2C-E recreationally, depending on how experienced the new user is with similar drugs, although the safety of this substance has not been scientifically established. Importantly, 2C-E is an extremely uncommon substance with a very short history of human use, and it is possible that lasting negative effects could be produced by any dose. Based on the current body of evidence and a comparison with the long-term effects of its close chemical analogue, mescaline, it seems reasonable to assume that 2C-E is not likely to produce such effects. # Law 2C-E is unscheduled in the United States; however, there are currently several cases pending in U.S. federal court against online vendors for selling research chemicals. These cases may address the question of whether this chemical could be legally defined as an analog of a scheduled substance. It is possible that it could be considered an analog of 2C-B or mescaline, in which case sale for human consumption or possession with the intent to ingest could be prosecuted as crimes under the Federal Analog Act. In Sweden, 2C-E has been controlled since Oct 1, 2004. The UK has the strictest laws in the EU on designer drugs. The Misuse Of Drugs Act was amended in 2002 to include a "catch most" clause outlawing every drug, and possible future drug, from the LSD (ergoline) and ecstasy (phenethylamine) chemical families (including 2C-E). The amendment is a virtual cut-and-paste from the books of the respected American biochemist Alexander Shulgin, who obtained a PhD from the University of California, Berkeley. Dr Shulgin, a former research chemist at the Dow Chemical Company, re-discovered the recipe for MDMA in 1976 and published the recipes for more than 170 designer drugs of his own invention. # Reference - ↑ Template:CitePiHKAL	2C-E 2C-E (2,5-dimethoxy-4-ethylphenethylamine) is a psychedelic drug and phenethylamine of the 2C family. It was first synthesized by Alexander Shulgin, sometimes used as an entheogen. It is commonly active in the 10-20 mg range, taken orally, and highly dose-sensitive. Insufflating (ie administering the chemical nasally) requires a much lower dose, typically not exceeding 5mgs, for noticeable effects, but tends to cause intense pain. Shulgin classified 2C-E as a member of the "magical half-dozen" in his book PiHKAL. Many have reported that the general effects of 2C-E are similar to those of the other psychedelic phenethylamines, but far more intense. Vivid hallucinations similar to those experienced while under the influence of LSD are common, and many reports would indicate that the effects of this particular chemical may be overly intense for those not well experienced with psychedelics [1]. However, for those who are familiar with the compound, oral doses of 30+ mg are not uncommon and often produce no additional side effects than those described by users of lower doses. # Properties 2,5-dimethoxy-4-ethylphenethylamine is a colorless oil. Crystalline forms are obtained as the amine salt by reacting the free base with a mineral acid, typically HCl. Shulgin does not report an exact boiling point for the free base, stating only that during one synthesis the fraction boiling between 90-100C at 0.25 mm/Hg pressure was collected and converted to the hydrochloride salt. Shulgin also does not report a melting point for the hydrochloride salt. The melting point of 184-185C previously reported in this article is incorrect. The 184-185C melt point value refers to the melting point of the hydrochloride salt of 5-ethoxy-4-ethyl-2-methoxyphenethylamine (2CE-5ETO in Shulgin's nomenclature). The Material Safety Data Sheet for a commercial sample of 2,5-dimethoxy-4-ethylphenethylamine hydrochloride reported the melting point as 247-249C. In the absence of a published melting point for a verified sample, the melting point is currently reported in this article as unknown. # Effects The total duration of 2C-E's effects is generally between six and ten hours for an average dose, with the plateau lasting between three and six hours. For such a dose, the onset of effects takes approximately twenty to ninety minutes and perception may be somewhat altered for up to a day after ingestion. In extreme cases where between seventy-five and one hundred milligrams of 2C-E were ingested, the duration of effects has exceeded twenty-four hours, with plateaus exceeding ten hours in length and an onset of effects within the first five minutes after the ingestion of the drug. A few users of very high doses have reported "never feeling the same again" after having used this drug. The concurrent use of SSRIs generally has a palliative effect upon both the intensity and duration of the effects of 2C-E during their plateau stage. As compared to similar compounds such as 2C-I and 2C-B, 2C-E is more likely to produce strong synaesthesia, sound distortion and an enhancement of the experience of music, and, most notably, visuals. Some users have also reported having mystical and "ego death" experiences while under the influence of 2C-E. While many users of lower doses of 2C-E have reported that it produces mainly closed-eye visuals, users of higher doses have compared its open-eye visuals with those produced by LSD; a significant proportion of these comparisons have favored the visual effects of 2C-E in terms both of their geometric complexity and in the variety of colors seen during an experience. The euphoriant effect shared by several other psychedelic phenethylamines seems only to have been reported relatively rarely by users of 2C-E; it has been described it as "difficult" by people who use it, including its inventor, Shulgin: At doses approximating or exceeding twenty to twenty-five milligrams, 2C-E can produce intensely colorful, highly complex, moving, fractal-like patterning, persian carpet-type visuals, three-dimensional visual effects, and, sometimes, visual patterning strongly resembling biological structures, such as vines, tentacles, and even eyeballs. The visual distortions produced by 2C-E are comparable in some respects to those produced by mescaline, and some users of both drugs have reported that the visual effects of 2C-E are more emphatic of color than are mescaline's corresponding effects, while mescaline's visuals are more emphatic of geometric structure. 2C-E's body load is a highly unusual one. Several users have described it, roughly, as a "profound feeling of general discomfort". It is sometimes characterized by urges to shift the position of one's body, strong nausea at high doses leading often to vomiting, itching, prolonged tensing of unusual combinations of muscle groups which can occur without the user's knowledge over a long period of time, diarrhoea, and an accompanying feeling of "disconnection from one's digestive tract". Some users report little or no body load on 2C-E, and describe in its stead strong euphoria; one user on Erowid reported that it produced a stronger euphoria than did cocaine, although this is extremely rare among 2C-E users. A negative body load is much more common than positive effects in this area. 2C-E's distortion of sounds is also quite profound, and includes the flanging of sounds, echoing, pitch shifting, and the perceived synthesis of new sounds not derived from one's immediate environment, such as scraping, drilling, and popping. Again, many of the more unusual distortions of sound are only experienced after the ingestion (or, rarely, insufflation) of a higher dose. 2C-E can also produce distortions in the user's perception of the passage of time leading to an illusion of moderate to extreme time dilation. Like all psychedelics, 2C-E produces a very altered state of consciousness; one unusual side of 2C-E's effects is that some users have reported experiencing "relatively normal thought processes" even while experiencing visual and auditory distortions. These users suggest, in other words, that 2C-E doesn't impair judgment as deeply as do many other psychedelics with otherwise-similar effects; however, these claims have not been tested in any controlled study. The wide difference between different users' accounts of the intensity, duration, and nature of the effects of 2C-E can largely be accounted for by users' highly varying dosage of the drug. Sites like erowid suggest that an average dose of 2C-E might be between ten and fifteen milligrams, and gives the highest "heavy" dose as twenty-five milligrams. Elsewhere on the Internet, and especially in various forums for users of psychedelics, users have reported taking up to between seventy-five and one hundred milligrams of 2C-E, and the ensuing experiences have invariably been extremely intense and very long (in some cases upwards of twenty-four hours in duration)[citation needed]. There have been no reported deaths from 2C-E use, so even these doses can be considered relatively safe considering how little is known about the long-term effects of the use of this substance. However, no experienced user of 2C-E has recommended doses this large for any newcomer; an appropriate starting dose might be between seven and twenty milligrams for someone intending to consume 2C-E recreationally, depending on how experienced the new user is with similar drugs, although the safety of this substance has not been scientifically established. Importantly, 2C-E is an extremely uncommon substance with a very short history of human use, and it is possible that lasting negative effects could be produced by any dose. Based on the current body of evidence and a comparison with the long-term effects of its close chemical analogue, mescaline, it seems reasonable to assume that 2C-E is not likely to produce such effects. # Law 2C-E is unscheduled in the United States; however, there are currently several cases pending in U.S. federal court against online vendors for selling research chemicals. These cases may address the question of whether this chemical could be legally defined as an analog of a scheduled substance. It is possible that it could be considered an analog of 2C-B or mescaline, in which case sale for human consumption or possession with the intent to ingest could be prosecuted as crimes under the Federal Analog Act. In Sweden, 2C-E has been controlled since Oct 1, 2004. The UK has the strictest laws in the EU on designer drugs. The Misuse Of Drugs Act was amended in 2002 to include a "catch most" clause outlawing every drug, and possible future drug, from the LSD (ergoline) and ecstasy (phenethylamine) chemical families (including 2C-E). The amendment is a virtual cut-and-paste from the books of the respected American biochemist Alexander Shulgin, who obtained a PhD from the University of California, Berkeley. Dr Shulgin, a former research chemist at the Dow Chemical Company, re-discovered the recipe for MDMA in 1976 and published the recipes for more than 170 designer drugs of his own invention. # Reference - ↑ Template:CitePiHKAL # External links - Project WebTryp, includes description of UK laws regarding Phenethylamines - Erowid 2C-E vault - 2C-E Entry in PIHKAL - 2C-E user survey Template:Hallucinogenic phenethylamines Template:PiHKAL sv:2C-E Template:WikiDoc Sources	https://www.wikidoc.org/index.php/2C-E
46b5933de55cdd8f375ead34d8e2ece752bf6a71	wikidoc	2C-G	2C-G 2C-G is a psychedelic phenethylamine of the 2C family. It was first synthesized by Alexander Shulgin, sometimes used as an entheogen. It has structural and pharmacodynamic properties similar to 2C-D and Ganesha. Like many of the phenethylamines in PiHKAL, 2C-G and its homologues (see below) have only been taken by Shulgin and a small test group, making it difficult to ensure completeness when describing effects. # Chemistry 2C-G is 3,4-dimethyl-2,5-dimethoxyphenethylamine, with the formula C12H19NO2. There are 209.284 grams of C12H19NO2 per mole (209.284 g/mol). # Dosage and Effects In Shulgin's book PiHKAL, the dosage range is listed as 20 to 35 mg. Effects are similar to the related Ganesha, and are extremely long lasting; the duration is 18-30 hours. Visual effects are muted or absent, and it is described in PiHKAL as an "insight-enhancher" . Unlike other members of the 2C- family, 2C-G is nearly as potent as its amphetamine cousin. # Homologues Several homologues of 2C-G were also synthesized by Shulgin. These include 2C-G-3, 2C-G-5, and 2C-G-N. Some, such as 2C-G-2 and 2C-G-4, are possible to synthesize in principle but impossible or extraordinarily difficult to do so in practice. # Law 2C-G and all of its homologues are unscheduled and uncontrolled in the United States, but possession and sales of 2C-G (and homologues) will probably be persecuted under the Federal Analog Act because of their structural similarities to 2C-B. 2C-G and all other compounds featuring in PiHKAL are Class A drugs in the United Kingdom. # Reference - ↑ Template:CitePiHKAL # Categorization	2C-G 2C-G is a psychedelic phenethylamine of the 2C family. It was first synthesized by Alexander Shulgin, sometimes used as an entheogen. It has structural and pharmacodynamic properties similar to 2C-D and Ganesha. Like many of the phenethylamines in PiHKAL, 2C-G and its homologues (see below) have only been taken by Shulgin and a small test group, making it difficult to ensure completeness when describing effects. # Chemistry 2C-G is 3,4-dimethyl-2,5-dimethoxyphenethylamine, with the formula C12H19NO2. There are 209.284 grams of C12H19NO2 per mole (209.284 g/mol). # Dosage and Effects In Shulgin's book PiHKAL, the dosage range is listed as 20 to 35 mg. Effects are similar to the related Ganesha, and are extremely long lasting; the duration is 18-30 hours. Visual effects are muted or absent, and it is described in PiHKAL as an "insight-enhancher" [1]. Unlike other members of the 2C* family, 2C-G is nearly as potent as its amphetamine cousin. # Homologues Several homologues of 2C-G were also synthesized by Shulgin. These include 2C-G-3, 2C-G-5, and 2C-G-N. Some, such as 2C-G-2 and 2C-G-4, are possible to synthesize in principle but impossible or extraordinarily difficult to do so in practice. # Law 2C-G and all of its homologues are unscheduled and uncontrolled in the United States, but possession and sales of 2C-G (and homologues) will probably be persecuted under the Federal Analog Act because of their structural similarities to 2C-B. 2C-G and all other compounds featuring in PiHKAL are Class A drugs in the United Kingdom. # Reference - ↑ Template:CitePiHKAL # Categorization Template:Hallucinogenic phenethylamines Template:PiHKAL	https://www.wikidoc.org/index.php/2C-G
34db0a111872000efdcb01e67e4b4b23c66ff84f	wikidoc	2C-I	2C-I 2C-I is a psychedelic drug and phenethylamine of the 2C family. It was developed and popularized by Alexander Shulgin. Its full chemical name is 2,5-dimethoxy-4-iodophenethylamine. It was described in Shulgin’s book PiHKAL. The drug is used both recreationally and as an entheogen but no medical or industrial uses have been reported yet. It is mostly commonly encountered in the form of its hydrochloride salt, a fluffy, sparkling white powder, and has also been pressed into tablet form. As it has only recently grown popular, slang terms for 2C-I vary with location (kite, iTrip etc). # Recreational use In the early 2000s, 2C-I in powder form became available for purchase from several online vendors of research chemicals in the United States, Asia, and elsewhere. In 2002 and 2003, tablets of 2C-I were being sold in nightclubs and at raves in Denmark and in the United Kingdom as a club drug, with tablets often being sold under the guise of being MDMA or a mixture of MDMA and LSD. # Effects 2C-I is generally taken orally, although it can also be insufflated, smoked, or administered rectally as well (though 2C-I often causes considerable pain upon insufflation). There have also been a few reports of intramuscular and intravenous injections. An oral recreational dose of 2C-I is commonly between 10mg and 25mg, although doses as low as 2mg have been reported to be active. The onset of effects usually occurs within an hour, and the effects of the drug typically last somewhere in the range of 5 to 12 hours. The effects of the drug are often described as quite similar to those of its chemical relative 2C-B, combining psychedelic or hallucinogenic effects typical of drugs such as LSD with the empathogenic or entactogenic effects of drugs such as MDMA (ecstasy). Some users report that the effects are more mental and less sensory than those of 2C-B. Users of 2C-I do, however, tend to report a physical stimulant effect, often quite strong. Although unpleasant physical side effects such as muscle tension, nausea, and vomiting have been reported, their incidence in the use of 2C-I appears to be less common than in the use of some of the other closely related phenethylamines such as 2C-T-2 and 2C-T-7. User reports have said that 2C-I may produce flashbacks in the weeks following its use. These flashbacks can last anywhere between seconds and hours, and manifest as a return of the hallucinogenic effects of the drug. Some users report being able to trigger the flashbacks at will. Note however that these flashbacks do not occur in the majority, but have simply been observed in a selection of users. They are thought to be similar in nature to LSD flashbacks, and are not harmful or even very remarkable (for a psychedelic drug). It may be interesting to note that experienced users of both LSD and 2C-I often state that the hallucinatory experience produced by both drugs is remarkably similar. # Potential Side Effects Virtually no research has been conducted on the toxicity of 2C-I. Unconfirmed reports have mentioned blood-clotting issues, vision problems including HPPD (Hallucinogen persisting perception disorder), muscle pain and fatigue, tingling of extremities, pain in the kidney areas (after repeated use) and symptoms of stroke. Seizures have been reported when 2C-I was taken in combination with Wellbutrin. Potential users of 2C-I should be aware that the long-term effects are virtually unknown. As of 2005, no official scientific studies of 2C-I users have been conducted, and no deaths have been attributed to the drug. There have been no reports of physical dependence or addiction. Comparisons with similar compounds suggest that use of 2C-I is unlikely to result in physical dependence. There is anecdotal evidence that 2C-I may cause persistent visual distortions for as long as a year in some users. This is an open topic of debate and has not been confirmed. # Law 2C-I is an illegal, controlled substance in several European nations, including Denmark, Germany, Greece, Ireland, and the United Kingdom. In December 2003, the European Council issued a binding order compelling all EU member states to ban 2C-I within three months. 2C-I is unscheduled and unregulated in the United States, however its close similarity in structure and effects to 2C-B could potentially subject possession and sale of 2C-I to prosecution under the Federal Analog Act, if it is intended for human consumption. This seems to be the tactic the federal government is taking in the wake of the DEA's Operation Web Tryp. A series of court cases in the US involving the prosecution of several online vendors is ongoing as of 2004.	2C-I Template:OrganicBox small 2C-I is a psychedelic drug and phenethylamine of the 2C family. It was developed and popularized by Alexander Shulgin. Its full chemical name is 2,5-dimethoxy-4-iodophenethylamine. It was described in Shulgin’s book PiHKAL. The drug is used both recreationally and as an entheogen but no medical or industrial uses have been reported yet. It is mostly commonly encountered in the form of its hydrochloride salt, a fluffy, sparkling white powder, and has also been pressed into tablet form. As it has only recently grown popular, slang terms for 2C-I vary with location (kite, iTrip etc). # Recreational use In the early 2000s, 2C-I in powder form became available for purchase from several online vendors of research chemicals in the United States, Asia, and elsewhere. In 2002 and 2003, tablets of 2C-I were being sold in nightclubs and at raves in Denmark and in the United Kingdom as a club drug, with tablets often being sold under the guise of being MDMA or a mixture of MDMA and LSD[citation needed]. # Effects 2C-I is generally taken orally, although it can also be insufflated, smoked, or administered rectally as well (though 2C-I often causes considerable pain upon insufflation). There have also been a few reports of intramuscular and intravenous injections. An oral recreational dose of 2C-I is commonly between 10mg and 25mg, although doses as low as 2mg have been reported to be active. The onset of effects usually occurs within an hour, and the effects of the drug typically last somewhere in the range of 5 to 12 hours. The effects of the drug are often described as quite similar to those of its chemical relative 2C-B, combining psychedelic or hallucinogenic effects typical of drugs such as LSD with the empathogenic or entactogenic effects of drugs such as MDMA (ecstasy). Some users report that the effects are more mental and less sensory than those of 2C-B. Users of 2C-I do, however, tend to report a physical stimulant effect, often quite strong. Although unpleasant physical side effects such as muscle tension, nausea, and vomiting have been reported, their incidence in the use of 2C-I appears to be less common than in the use of some of the other closely related phenethylamines such as 2C-T-2 and 2C-T-7. User reports have said that 2C-I may produce flashbacks in the weeks following its use. These flashbacks can last anywhere between seconds and hours, and manifest as a return of the hallucinogenic effects of the drug. Some users report being able to trigger the flashbacks at will.[citation needed] Note however that these flashbacks do not occur in the majority, but have simply been observed in a selection of users. They are thought to be similar in nature to LSD flashbacks, and are not harmful or even very remarkable (for a psychedelic drug). It may be interesting to note that experienced users of both LSD and 2C-I often state that the hallucinatory experience produced by both drugs is remarkably similar. # Potential Side Effects Virtually no research has been conducted on the toxicity of 2C-I. Unconfirmed reports have mentioned blood-clotting issues, vision problems including HPPD (Hallucinogen persisting perception disorder), muscle pain and fatigue, tingling of extremities, pain in the kidney areas (after repeated use) and symptoms of stroke. Seizures have been reported when 2C-I was taken in combination with Wellbutrin. Potential users of 2C-I should be aware that the long-term effects are virtually unknown. As of 2005, no official scientific studies of 2C-I users have been conducted, and no deaths have been attributed to the drug. There have been no reports of physical dependence or addiction. Comparisons with similar compounds suggest that use of 2C-I is unlikely to result in physical dependence. There is anecdotal evidence that 2C-I may cause persistent visual distortions for as long as a year in some users.[citation needed] This is an open topic of debate and has not been confirmed. # Law 2C-I is an illegal, controlled substance in several European nations, including Denmark, Germany, Greece, Ireland, and the United Kingdom. In December 2003, the European Council issued a binding order compelling all EU member states to ban 2C-I within three months. 2C-I is unscheduled and unregulated in the United States, however its close similarity in structure and effects to 2C-B could potentially subject possession and sale of 2C-I to prosecution under the Federal Analog Act, if it is intended for human consumption. This seems to be the tactic the federal government is taking in the wake of the DEA's Operation Web Tryp. A series of court cases in the US involving the prosecution of several online vendors is ongoing as of 2004.	https://www.wikidoc.org/index.php/2C-I
61bf4f2820aef1cf9d8d7f64fc49e49805d40de8	wikidoc	2C-N	2C-N 2C-N, or 2,5-Dimethoxy-4-nitrophenethylamine, is a psychedelic phenethylamine of the 2C family. It was first synthesized by Alexander Shulgin, sometimes used as an entheogen. # Chemistry The full name of the chemical is 2-(2,5-dimethoxy-4-nitrophenyl)ethanamine. Salts of 2C-N have a bright yellow to orange color due to the presence of the nitro group, unlike all other members of the 2C family in which the salts are white. # Dosage In his book PiHKAL (Phenethylamines I Have Known and Loved), Shulgin lists the dosage range as 100-150 mg. 2C-N is generally taken orally, and effects typically last 4 to 6 hours. # Dangers There have been no reported deaths or hospitalizations from 2C-N, but its safety profile is unknown. # Law 2C-N is unscheduled and uncontrolled in the United States, but possession and sales of 2C-N may potentially be prosecuted under the Federal Analog Act because of its structural similarities to 2C-T-7 or 2C-B. The legality of 2C-N is under scrutiny as of July 2004, due to Operation Web Tryp. 2C-N and most (possibly all) other compounds featuring in PiHKAL are illegal drugs in the United Kingdom. # Reference - ↑ Template:CitePiHKAL	2C-N 2C-N, or 2,5-Dimethoxy-4-nitrophenethylamine, is a psychedelic phenethylamine of the 2C family. It was first synthesized by Alexander Shulgin, sometimes used as an entheogen. # Chemistry The full name of the chemical is 2-(2,5-dimethoxy-4-nitrophenyl)ethanamine. Salts of 2C-N have a bright yellow to orange color due to the presence of the nitro group, unlike all other members of the 2C family in which the salts are white. # Dosage In his book PiHKAL (Phenethylamines I Have Known and Loved), Shulgin lists the dosage range as 100-150 mg. 2C-N is generally taken orally, and effects typically last 4 to 6 hours.[1] # Dangers There have been no reported deaths or hospitalizations from 2C-N, but its safety profile is unknown. # Law 2C-N is unscheduled and uncontrolled in the United States, but possession and sales of 2C-N may potentially be prosecuted under the Federal Analog Act because of its structural similarities to 2C-T-7 or 2C-B. The legality of 2C-N is under scrutiny as of July 2004, due to Operation Web Tryp. 2C-N and most (possibly all) other compounds featuring in PiHKAL are illegal drugs in the United Kingdom. # Reference - ↑ Template:CitePiHKAL	https://www.wikidoc.org/index.php/2C-N
0b28fb0eb31dc2ba5c5bb91702a54c7365e17219	wikidoc	2C-O	2C-O 2C-O (or 2,4,5-trimethoxyphenethylamine) is a phenethylamine of the 2C family. It is also a positional isomer of mescaline and was first synthesized by Jansen in 1931. This chemical is also called 2,4,5-TMPEA. It has structurally similar to the drugs mescaline and 2C-D. # Chemistry 2C-O is in a class of compounds commonly known as phenethylamines, and the full chemical name is 2-(2,4,5-trimethoxyphenyl)ethanamine. # Effects Although not centrally active itself, 2,4,5-TMPEA appeared to potentiate the action of mescaline when employed as pretreatment 45 minutes prior to the administration of mescaline. # Dangers The toxicity of 2C-O is not known. # Law 2C-O is unscheduled and unregulated in the United States, however its close similarity in structure to mescaline and 2C-B could potentially subject possession and sale of 2C-O to prosecution under the Federal Analog Act. 2C-O and all other compounds featuring in PiHKAL are Class A drugs in the United Kingdom. # Reference - ↑ Template:CitePiHKAL	2C-O 2C-O (or 2,4,5-trimethoxyphenethylamine) is a phenethylamine of the 2C family. It is also a positional isomer of mescaline and was first synthesized by Jansen in 1931. This chemical is also called 2,4,5-TMPEA. It has structurally similar to the drugs mescaline and 2C-D. # Chemistry 2C-O is in a class of compounds commonly known as phenethylamines, and the full chemical name is 2-(2,4,5-trimethoxyphenyl)ethanamine. # Effects Although not centrally active itself, 2,4,5-TMPEA appeared to potentiate the action of mescaline when employed as pretreatment 45 minutes prior to the administration of mescaline.[1] # Dangers The toxicity of 2C-O is not known. # Law 2C-O is unscheduled and unregulated in the United States, however its close similarity in structure to mescaline and 2C-B could potentially subject possession and sale of 2C-O to prosecution under the Federal Analog Act. 2C-O and all other compounds featuring in PiHKAL are Class A drugs in the United Kingdom. # Reference - ↑ Template:CitePiHKAL	https://www.wikidoc.org/index.php/2C-O
d0ffb996e1bdc52e79c8983cb0d4f9504833b4b4	wikidoc	2C-P	2C-P 2C-P is an entheogenic phenethylamine and 2C compound first synthesized by Alexander Shulgin. # Chemistry 2C-P is 2,5-dimethoxy-4-(n)-propylphenethylamine. The full name of the chemical is 2-(2,5-dimethoxy-4-propylphenyl)ethanamine. # Dosage In his book 'PiHKAL' (Phenethylamines I Have Known and Loved), Shulgin listed 2C-P's dosage between 6-10 mg, with 16 mg being labelled an "overdose." 2C-P is one of the most potent in the 2C family of psychedelics, rivalled only by 2C-TFM. A consistent feature with 2C-P is a steep dose/response curve. As little as 1 to 2 mg can be the difference between effects which are moderate and enjoyable, and those which are excessive and frightening. The need for an accurate milligram scale is of the utmost importance with 2C-P. # Effects 2C-P produces intense hallucinogenic, psychedelic, and entheogenic effects. The drug has a very slow onset if ingested, and peak effects do not occur for 3 to 5 hours. A 2C-P experience can last anywhere between 10 to 16 hours, or even longer with higher dosages. Many have reported that the effects of 2C-P are similar to other phenethylamines, especially 2C-E, but are significantly longer lasting. Intense visionary experiences similar to those of LSD have been reported, and many reports indicate that the effects of this particular chemical may be overwhelming for those not well experienced with psychedelics. # Reference - ↑ Template:CitePiHKAL	2C-P 2C-P is an entheogenic phenethylamine and 2C compound first synthesized by Alexander Shulgin. # Chemistry 2C-P is 2,5-dimethoxy-4-(n)-propylphenethylamine. The full name of the chemical is 2-(2,5-dimethoxy-4-propylphenyl)ethanamine. # Dosage In his book 'PiHKAL' (Phenethylamines I Have Known and Loved), Shulgin listed 2C-P's dosage between 6-10 mg, with 16 mg being labelled an "overdose." 2C-P is one of the most potent in the 2C family of psychedelics, rivalled only by 2C-TFM. A consistent feature with 2C-P is a steep dose/response curve. As little as 1 to 2 mg can be the difference between effects which are moderate and enjoyable, and those which are excessive and frightening. The need for an accurate milligram scale is of the utmost importance with 2C-P. # Effects 2C-P produces intense hallucinogenic, psychedelic, and entheogenic effects. The drug has a very slow onset if ingested, and peak effects do not occur for 3 to 5 hours. A 2C-P experience can last anywhere between 10 to 16 hours, or even longer with higher dosages.[1] Many have reported that the effects of 2C-P are similar to other phenethylamines, especially 2C-E, but are significantly longer lasting. Intense visionary experiences similar to those of LSD have been reported, and many reports indicate that the effects of this particular chemical may be overwhelming for those not well experienced with psychedelics. # Reference - ↑ Template:CitePiHKAL # External links - 2C-P Entry in PIHKAL # Categorization Template:Hallucinogenic phenethylamines Template:PiHKAL Template:Hallucinogen-stub Template:WikiDoc Sources	https://www.wikidoc.org/index.php/2C-P
6d99d3b6ee629231e63ae03f97e9eafbbc71aa82	wikidoc	2C-T	2C-T 2C-T (or 4-methylthio-2,5-DMPEA) is a psychedelic and hallucinogenic drug of the 2C family. It is used by some as an entheogen. It has structural and pharmacodynamic properties similar to the drugs mescaline and 2C-T-2. It was first synthesized and studied through a collaboration between David E. Nichols and Alexander Shulgin. # Chemistry 2C-T is in a class of compounds commonly known as phenethylamines, and is the 4-methylthio analogue of 2C-O, a positional isomer of mescaline. It is also the 2C analog of Aleph. The full name of the chemical is 4-methylthio-2,5-dimethoxyphenethylamine. The CAS number of 2C-T is 61638-09-3. # Effects 2C-T's active dosage is around 75-150mg and produces mescaline and MDMA-like effects that may last up to 6 hours. # Pharmacology The mechanism that produces 2C-T’s hallucinogenic and entheogenic effects has not been specifically established, however it is most likely to result from action as a 5-HT2A serotonin receptor agonist in the brain, a mechanism of action shared by all of the hallucinogenic tryptamines and phenethylamines for which the mechanism of action is known. # Dangers The toxicity of 2C-T is not well documented. 2C-T is considerably less potent than other related drugs such as 2C-T-7, but it may be expected that at higher doses it would display similar toxicity to that of other phenethylamines of the 2C-T family. Other phenethylamine derivatives substituted with an alkylthio group at the 4 position such as 2C-T-7 and 4-MTA are known to act as selective monoamine oxidase A inhibitors, a side effect which can lead to lethal serotonin syndrome when they are combined with stimulant drugs. Most confirmed fatalities involving 2C-T drugs involve their combination with other hard drugs such as alcohol, ecstasy or cocaine. # Popularity 2C-T is almost unknown on the black market although it has rarely been sold by "research chemical" companies. Limited accounts of 2C-T can be found in the book PiHKAL. # Legality 2C-T is unscheduled and unregulated in the United States; however its close similarity in structure and effects to 2C-T-7 could potentially subject possession and sale of 2C-T to prosecution under the Federal Analog Act. This seems to be the tack the federal government is taking in the wake of the DEA's Operation Web Tryp. A series of Court Cases in the US involving the prosecution of several online vendors were commenced in 2004 and resulted in a number of convictions. # Reference - ↑ Template:CitePiHKAL	2C-T 2C-T (or 4-methylthio-2,5-DMPEA) is a psychedelic and hallucinogenic drug of the 2C family. It is used by some as an entheogen. It has structural and pharmacodynamic properties similar to the drugs mescaline and 2C-T-2. It was first synthesized and studied through a collaboration between David E. Nichols and Alexander Shulgin. # Chemistry 2C-T is in a class of compounds commonly known as phenethylamines, and is the 4-methylthio analogue of 2C-O, a positional isomer of mescaline. It is also the 2C analog of Aleph. The full name of the chemical is 4-methylthio-2,5-dimethoxyphenethylamine. The CAS number of 2C-T is 61638-09-3. # Effects 2C-T's active dosage is around 75-150mg and produces mescaline and MDMA-like effects that may last up to 6 hours.[1] # Pharmacology The mechanism that produces 2C-T’s hallucinogenic and entheogenic effects has not been specifically established, however it is most likely to result from action as a 5-HT2A serotonin receptor agonist in the brain, a mechanism of action shared by all of the hallucinogenic tryptamines and phenethylamines for which the mechanism of action is known. # Dangers The toxicity of 2C-T is not well documented. 2C-T is considerably less potent than other related drugs such as 2C-T-7, but it may be expected that at higher doses it would display similar toxicity to that of other phenethylamines of the 2C-T family. Other phenethylamine derivatives substituted with an alkylthio group at the 4 position such as 2C-T-7 and 4-MTA are known to act as selective monoamine oxidase A inhibitors, a side effect which can lead to lethal serotonin syndrome when they are combined with stimulant drugs. Most confirmed fatalities involving 2C-T drugs involve their combination with other hard drugs such as alcohol, ecstasy or cocaine. # Popularity 2C-T is almost unknown on the black market although it has rarely been sold by "research chemical" companies. Limited accounts of 2C-T can be found in the book PiHKAL. # Legality 2C-T is unscheduled and unregulated in the United States; however its close similarity in structure and effects to 2C-T-7 could potentially subject possession and sale of 2C-T to prosecution under the Federal Analog Act. This seems to be the tack the federal government is taking in the wake of the DEA's Operation Web Tryp. A series of Court Cases in the US involving the prosecution of several online vendors were commenced in 2004 and resulted in a number of convictions. # Reference - ↑ Template:CitePiHKAL	https://www.wikidoc.org/index.php/2C-T
4c750664ccc1d5d288c116f7857d07c682486a64	wikidoc	A1CF	A1CF APOBEC1 complementation factor is a protein that in humans is encoded by the A1CF gene. # Gene Alternative splicing occurs at this locus and three full-length transcript variants, encoding three distinct isoforms, have been described. Additional splicing has been observed but the full-length nature of these variants has not been determined. # Function Mammalian apolipoprotein B mRNA undergoes site-specific C to U deamination, which is mediated by a multi-component enzyme complex containing a minimal core composed of APOBEC1 and a complementation factor encoded by this gene. The gene product has three non-identical RNA recognition motifs and belongs to the hnRNP R family of RNA-binding proteins. It has been proposed that this complementation factor functions as an RNA-binding subunit and docks APOBEC1 to deaminate the upstream cytidine. Studies suggest that the protein may also be involved in other RNA editing or RNA processing events. Its deletion results in lethality in mice. # Interactions A1CF has been shown to interact with APOBEC1, CUGBP2, and SYNCRIP.	A1CF APOBEC1 complementation factor is a protein that in humans is encoded by the A1CF gene.[1][2][3] # Gene Alternative splicing occurs at this locus and three full-length transcript variants, encoding three distinct isoforms, have been described. Additional splicing has been observed but the full-length nature of these variants has not been determined.[3] # Function Mammalian apolipoprotein B mRNA undergoes site-specific C to U deamination, which is mediated by a multi-component enzyme complex containing a minimal core composed of APOBEC1 and a complementation factor encoded by this gene.[4] The gene product has three non-identical RNA recognition motifs and belongs to the hnRNP R family of RNA-binding proteins. It has been proposed that this complementation factor functions as an RNA-binding subunit and docks APOBEC1 to deaminate the upstream cytidine. Studies suggest that the protein may also be involved in other RNA editing or RNA processing events.[3] Its deletion results in lethality in mice.[5] # Interactions A1CF has been shown to interact with APOBEC1,[6][7] CUGBP2,[8] and SYNCRIP.[9][6]	https://www.wikidoc.org/index.php/A1CF
67b0cccadca8d45c59ceebb89f725c864a8f353f	wikidoc	AATK	AATK Serine/threonine-protein kinase LMTK1 (also known as Apoptosis-associated tyrosine kinase) is an enzyme that in humans is encoded by the (AATK) gene. # Structure and expression The gene was identified in 1998. It is located on chromosome 17 (17q25.3) and is expressed in the pancreas, kidney, brain and lungs. The protein is composed of 1,207 amino acids. # Function The protein contains a tyrosine kinase domain at the N-terminal end and a proline-rich domain at the c-terminal end. Studies of the mouse homologue have indicated that it may be necessary for the induction of growth arrest and/or apoptosis of myeloid precursor cells. It may also have a role in inducing differentiation in neuronal cells. Its suppressive role on melanoma development has been reported recently. AATK is thought to indirectly inhibit the SPAK/WNK4 activation of the Na-K-Cl cotransporter.	AATK Serine/threonine-protein kinase LMTK1 (also known as Apoptosis-associated tyrosine kinase) is an enzyme that in humans is encoded by the (AATK) gene.[1][2][3] # Structure and expression The gene was identified in 1998. It is located on chromosome 17 (17q25.3) and is expressed in the pancreas, kidney, brain and lungs. The protein is composed of 1,207 amino acids.[1][2] # Function The protein contains a tyrosine kinase domain at the N-terminal end and a proline-rich domain at the c-terminal end. Studies of the mouse homologue have indicated that it may be necessary for the induction of growth arrest and/or apoptosis of myeloid precursor cells. It may also have a role in inducing differentiation in neuronal cells.[3][4] Its suppressive role on melanoma development has been reported recently.[5] AATK is thought to indirectly inhibit the SPAK/WNK4 activation of the Na-K-Cl cotransporter.[6]	https://www.wikidoc.org/index.php/AATK
aec7a4db77bfe8231237376819f62388ab81248f	wikidoc	ABAT	ABAT 4-Aminobutyrate aminotransferase is a protein that in humans is encoded by the ABAT gene. This gene is located in chromosome 16 at position of 13.2. This gene has also different name, to give some are GABA, GABAT, 4-aminobutyrate transaminase, NPD009 and etc. This gene is mainly and abundant located in neuronal tissues. 4-Aminobutyrate aminotransferase belongs to group of pyridoxal 5-phosphate-dependent enzyme which activates a large portion giving reaction to amino acids. ABAT is made up of two monomers of enzymes where each subunit has a molecular weight of 50kDa. It is identified that almost tierce of human synapses have GABA. GABA is a neurotransmitter that has different roles in different regiions of the central and peripheral nervous systems. It can be found also in some tissues that do not have neurons. In addition, GAD and GABA-AT are responsible in regulating the concentration of GABA. # Characteristic GABA’s feature is that it does not fluorescent nor electroactive which is why it is hard to determine the reaction of enzymes because no peroxidase and dehydrogenase was identified. One characteristic of GABA is having low lipophilic which results in the difficulty to cross the blood brain barrier. A lot of researchers have been trying to discover molecules that have a property of high lipophilicity. The quantification of GABA concentration during cell activity needs to have high spatial and temporal resolution. As before, high performance liquid chromatography (HPLC) was used in quantifying GABA concentration levels. In present time, GABA is now analyze, measured in small volume with a short period of time with the use of electrochemiluminescence. GABA acts as a tropic factor which then affects some cell activity such as rapid cell reproduction, cell death and differentiation. Intracellular communication is also one of the many functions of GABA outside the nervous system. # Function 4-Aminobutyrate aminotransferase (ABAT) is responsible for catabolism of gamma-aminobutyric acid (GABA), an important, mostly inhibitory neurotransmitter in the central nervous system, into succinic semialdehyde. The active enzyme is a homodimer of 50-kD subunits complexed to pyridoxal-5-phosphate. The protein sequence is over 95% similar to the pig protein. ABAT in liver and brain is controlled by 2 codominant alleles with a frequency in a Caucasian population of 0.56 and 0.44. GABA acts as a tropic factor which then affects some cell activity such as rapid cell reproduction, cell death and differentiation. Intracellular communication is also one of the many functions of GABA outside the nervous system. GABA-transaminaze enzyme production was made of ABAT gene command. The main function of ABAT acts as inhibition (neurotransmitter), where it prevents overloading activity of the brain from large amount of signals. ABAT activates the beginning of deterioration of GABA. Likewise, suppression of ABAT results in depletion of transient lower esophageal sphincter relaxation (TLESR) and acid reflux activity.Treating of GERD is possible means of suppressing ABAT’s physiology. # ABAT Deficiency ABAT defect is uncommon disorder. The signs and symptoms of this deficiency were observed from a Dutch family, two of the siblings, and a 6 month pediatric Japanese. These patients have same signs and symptoms that were observed. This include low muscle tone or known as floppy baby syndrome, over responsive reflexes and developmental delay. The ABAT deficiency phenotype includes psychomotor retardation, hypotonia, hyperreflexia, lethargy, refractory seizures, and EEG abnormalities. Multiple alternatively spliced transcript variants encoding the same protein isoform have been found for this gene. Abnormal GABA-transaminaze enzyme results in encephalopathy which is observed in pediatric patients and this deficiency have life expectancy of less than 2 years and some survived more than the given life expectancy.Abnormal protein that is being set free from uncontrolled amount of GABA will affect the growth of individual (growth hormone). Decrease level of GABA concentration results in convulsion. # Medicine Vigabatrin is a drug that is irreparably suppresses GABA transaminase that causes increased amount of GABA in the brain. # Discovery In a recent study, it was found out that the increase amount of GABA will stop the consequences of drug addiction. The suppression of ABAT which causing the amount of GABA to increase has a connection to children with those suffer from movement disability. This gene is also link as one genetic cause of GERD. ABAT has been proved that it is important in mitochondrial nucleoside.	ABAT 4-Aminobutyrate aminotransferase is a protein that in humans is encoded by the ABAT gene.[1] This gene is located in chromosome 16 at position of 13.2.[2] This gene has also different name, to give some are GABA, GABAT, 4-aminobutyrate transaminase, NPD009 and etc.[2] This gene is mainly and abundant located in neuronal tissues.[3] 4-Aminobutyrate aminotransferase belongs to group of pyridoxal 5-phosphate-dependent enzyme which activates a large portion giving reaction to amino acids.[4] ABAT is made up of two monomers of enzymes where each subunit has a molecular weight of 50kDa.[5] It is identified that almost tierce of human synapses have GABA.[2] GABA is a neurotransmitter that has different roles in different regiions of the central and peripheral nervous systems. It can be found also in some tissues that do not have neurons.[2] In addition, GAD and GABA-AT are responsible in regulating the concentration of GABA.[6] # Characteristic GABA’s feature is that it does not fluorescent nor electroactive which is why it is hard to determine the reaction of enzymes because no peroxidase and dehydrogenase was identified.[7] One characteristic of GABA is having low lipophilic which results in the difficulty to cross the blood brain barrier. A lot of researchers have been trying to discover molecules that have a property of high lipophilicity.[6] The quantification of GABA concentration during cell activity needs to have high spatial and temporal resolution. As before, high performance liquid chromatography (HPLC) was used in quantifying GABA concentration levels. In present time, GABA is now analyze, measured in small volume with a short period of time with the use of electrochemiluminescence.[7] GABA acts as a tropic factor which then affects some cell activity such as rapid cell reproduction, cell death and differentiation. Intracellular communication is also one of the many functions of GABA outside the nervous system.[7] # Function 4-Aminobutyrate aminotransferase (ABAT) is responsible for catabolism of gamma-aminobutyric acid (GABA), an important, mostly inhibitory neurotransmitter in the central nervous system, into succinic semialdehyde. The active enzyme is a homodimer of 50-kD subunits complexed to pyridoxal-5-phosphate. The protein sequence is over 95% similar to the pig protein. ABAT in liver and brain is controlled by 2 codominant alleles with a frequency in a Caucasian population of 0.56 and 0.44.[1] GABA acts as a tropic factor which then affects some cell activity such as rapid cell reproduction, cell death and differentiation. Intracellular communication is also one of the many functions of GABA outside the nervous system.[7] GABA-transaminaze enzyme production was made of ABAT gene command. The main function of ABAT acts as inhibition (neurotransmitter), where it prevents overloading activity of the brain from large amount of signals.[2] ABAT activates the beginning of deterioration of GABA. Likewise, suppression of ABAT results in depletion of transient lower esophageal sphincter relaxation (TLESR) and acid reflux activity.Treating of GERD is possible means of suppressing ABAT’s physiology.[3] # ABAT Deficiency ABAT defect is uncommon disorder. The signs and symptoms of this deficiency were observed from a Dutch family, two of the siblings, and a 6 month pediatric Japanese. These patients have same signs and symptoms that were observed. This include low muscle tone or known as floppy baby syndrome, over responsive reflexes and developmental delay.[8] The ABAT deficiency phenotype includes psychomotor retardation, hypotonia, hyperreflexia, lethargy, refractory seizures, and EEG abnormalities. Multiple alternatively spliced transcript variants encoding the same protein isoform have been found for this gene.[1] Abnormal GABA-transaminaze enzyme results in encephalopathy which is observed in pediatric patients and this deficiency have life expectancy of less than 2 years and some survived more than the given life expectancy.Abnormal protein that is being set free from uncontrolled amount of GABA will affect the growth of individual (growth hormone).[2] Decrease level of GABA concentration results in convulsion.[9] # Medicine Vigabatrin is a drug that is irreparably suppresses GABA transaminase that causes increased amount of GABA in the brain.[10] # Discovery In a recent study, it was found out that the increase amount of GABA will stop the consequences of drug addiction.[11] The suppression of ABAT which causing the amount of GABA to increase has a connection to children with those suffer from movement disability.[8] This gene is also link as one genetic cause of GERD.[3] ABAT has been proved that it is important in mitochondrial nucleoside.[9]	https://www.wikidoc.org/index.php/ABAT
0458fc82e0e38561758dd7e7e512b2d3e8301ad5	wikidoc	ABI1	ABI1 Abl interactor 1 also known as Abelson interactor 1 (Abi-1) is a protein that in humans is encoded by the ABI1 gene. # Function Abl interactor 1 has been found to form a complex with EPS8 and SOS1, and is thought to be involved in the transduction of signals from Ras to Rac. In addition, the encoded protein may play a role in the regulation of EGF-induced Erk pathway activation as well as cytoskeletal reorganization and EGFR signaling. Several transcript variants encoding multiple isoforms have been found for this gene. Abi1 is adaptor protein. It interacts with c-Abl and WAVE2 which is an actin polymerization regulator. It is known that Abi1 enhances the phosphorylation of WAVE2 by c-Abl. The phosphorylation of c-Abl promotes actin polymerization. Furthermore, Abi1 is a component of the WAVE complex. Some research has shown that knockdown of Abi1 by siRNA promoted degradation of WAVE complex proteins. # Interactions ABI1 has been shown to interact with ENAH, NCKAP1, EPS8, and SOS1.	ABI1 Abl interactor 1 also known as Abelson interactor 1 (Abi-1) is a protein that in humans is encoded by the ABI1 gene.[1][2] # Function Abl interactor 1 has been found to form a complex with EPS8 and SOS1, and is thought to be involved in the transduction of signals from Ras to Rac. In addition, the encoded protein may play a role in the regulation of EGF-induced Erk pathway activation as well as cytoskeletal reorganization and EGFR signaling. Several transcript variants encoding multiple isoforms have been found for this gene.[3] Abi1 is adaptor protein. It interacts with c-Abl and WAVE2 which is an actin polymerization regulator. It is known that Abi1 enhances the phosphorylation of WAVE2 by c-Abl. The phosphorylation of c-Abl promotes actin polymerization. Furthermore, Abi1 is a component of the WAVE complex. Some research has shown that knockdown of Abi1 by siRNA promoted degradation of WAVE complex proteins.[citation needed] # Interactions ABI1 has been shown to interact with ENAH,[4] NCKAP1,[5] EPS8,[2][4][5][6][7] and SOS1.[8]	https://www.wikidoc.org/index.php/ABI1
533ec6db3e6b5bd3118d04c84a7d4d85e541f3aa	wikidoc	ABL2	ABL2 Tyrosine-protein kinase ABL2 also known as Abelson-related gene (Arg) is an enzyme that in humans is encoded by the ABL2 gene. # Function ABL2 is a cytoplasmic tyrosine kinase which is closely related to but distinct from ABL1. The similarity of the proteins includes the tyrosine kinase domains and extends amino-terminal to include the SH2 and SH3 domains. ABL2 is expressed in both normal and tumor cells. The expression of ABL2 gene is higher in KRAS mutant non-small cell lung cancer. The ABL2 gene product is expressed as two variants bearing different amino termini, both approximately 12-kb in length. # Interactions ABL2 has been shown to interact with three proteins: Abl gene, catalase, and SORBS2. The protein Abl gene is also known as abelson murine leukemia viral oncogene homolog 1 and is a protein that is encoded by the human ABL1 gene. Catalase is a common enzyme that catalyzes the decomposition of hydrogen peroxide to water and oxygen. SORBS2 is also known as Sorbin and SH3 domain-containing protein 2 and is a protein encoded by the SORBS2 gene in humans.	ABL2 Tyrosine-protein kinase ABL2 also known as Abelson-related gene (Arg) is an enzyme that in humans is encoded by the ABL2 gene.[1][2] # Function ABL2 is a cytoplasmic tyrosine kinase which is closely related to but distinct from ABL1. The similarity of the proteins includes the tyrosine kinase domains and extends amino-terminal to include the SH2 and SH3 domains. ABL2 is expressed in both normal and tumor cells. The expression of ABL2 gene is higher in KRAS mutant non-small cell lung cancer.[3] The ABL2 gene product is expressed as two variants bearing different amino termini, both approximately 12-kb in length.[2] # Interactions ABL2 has been shown to interact with three proteins: Abl gene,[4] catalase,[5] and SORBS2.[6] The protein Abl gene is also known as abelson murine leukemia viral oncogene homolog 1 and is a protein that is encoded by the human ABL1 gene.[7] Catalase is a common enzyme that catalyzes the decomposition of hydrogen peroxide to water and oxygen.[8] SORBS2 is also known as Sorbin and SH3 domain-containing protein 2 and is a protein encoded by the SORBS2 gene in humans.[2][6][9]	https://www.wikidoc.org/index.php/ABL2
c1e9a24bd264b84c643c28fcf61b87e73ec2cf70	wikidoc	ABVD	ABVD # Overview ABVD is a chemotherapy regimen used in the first-line treatment of Hodgkin's lymphoma. It consists of concurrent treatment with the chemotherapy drugs adriamycin, bleomycin, vinblastine and dacarbazine. # Indications As of 2006, ABVD is widely used as the initial chemotherapy treatment for newly diagnosed Hodgkin's lymphoma. The other chemotherapy regimen that is widely used in this setting is the Stanford V regimen. # History Prior to the mid-1960's, advanced-stage Hodgkin disease was treated with single-agent chemotherapy, with fairly dismal long-term survival and cure rates. With advances in the understanding of chemotherapy resistance and the development of combination chemotherapy, Vincent DeVita and George Canellos at the National Cancer Institute (United States) developed the MOPP regimen. This combination of mechlorethamine, vincristine (Oncovin), procarbazine, and prednisone proved capable of curing almost 70% of patients with advanced-stage Hodgkin's lymphoma. While MOPP was remarkably successful in curing advanced Hodgkin's lymphoma, its toxicity remained significant. Aside from bone marrow suppression, frequent side effects included nerve injury caused by vincristine and allergic reactions to procarbazine. Long-term effects were also a concern, as patients were often cured and could expect long survival after chemotherapy. Infertility was a major long-term side effect, and even more seriously, the risk of developing treatment-related myelodysplasia or acute leukemia was increased up to 14-fold in patients who received MOPP. These treatment-related hematological malignancies peaked at 5 to 9 years after treatment for Hodgkin's lymphoma, and were associated with a dismally poor prognosis. ## Development of ABVD Therefore, alternate regimens were tested in an attempt to avoid alkylating agents (such as mechlorethamine), which were thought to be responsible for many of the long-term side effects of MOPP. ABVD was developed as a potentially less toxic and more effective alternative to MOPP; initial results with ABVD were published in 1975 by an Italian group led by Bonadonna. A number of trials then compared ABVD to previous regimens for Hodgkin's lymphoma. A large trial by CALGB suggested that ABVD was superior to MOPP, with a higher rate of overall response, less hematologic toxicity, better relapse-free survival, and better outcomes after relapse in the patients treated with ABVD. Later studies confirmed the superiority of ABVD in terms of effectiveness, and also demonstrated that late side effects, such as treatment-related acute leukemia, were less common with ABVD as compared to MOPP. Taken together, these results led ABVD to the replacement of MOPP with ABVD in the first-line treatment of Hodgkin's lymphoma. # Administration One cycle of ABVD chemotherapy is typically given over 4 weeks, with two doses in each cycle (on day 1 and day 15). All four of the chemotherapy drugs are given intravenously. ABVD chemotherapy is usually given in the outpatient setting — that is, it does not require hospitalization. Typical dosages for one 28-day cycle of ABVD are as follows - Adriamycin 25 mg/m2 IV on days 1 and 15 - Bleomycin 10 mg/m2 IV on days 1 and 15 - Vinblastine 6 mg/m2 IV on days 1 and 15 - Dacarbazine 375 mg/m2 IV on days 1 and 15 The total number of cycles given depends upon the stage of the disease and how well the patient tolerates chemotherapy. Doses may be delayed because of neutropenia, thrombocytopenia, or other side effects. # Side effects In the relative spectrum of cancer chemotherapy, ABVD is not a particularly toxic regimen. Side effects of ABVD can be divided into acute (those occurring while receiving chemotherapy) and delayed (those occurring months to years after completion of chemotherapy). Delayed side effects have assumed particular importance because many patients treated for Hodgkin's lymphoma are cured and can expect long lives after completion of chemotherapy. ## Acute side effects - Hair loss, or alopecia, is a fairly common but not universal side effect of ABVD. Hair that is lost returns in the months after completion of chemotherapy. - Nausea and vomiting can occur with ABVD, although treatments for chemotherapy-induced nausea and vomiting have improved substantially (see Supportive care below). - Low blood counts, or myelosuppression, occur about 50% of the time with ABVD. Blood cell growth factors are sometimes used to prevent this (see Supportive care below). Blood counts are checked frequently while receiving chemotherapy. Any fever or sign of infection that develops needs to be promptly evaluated; severe infections can develop rapidly in a person with a low white blood cell count due to chemotherapy. - Allergic reactions to bleomycin can occur. A small test dose of bleomycin is often given prior to the first round of ABVD to screen for patients who may be allergic. - Neuropathy Numbness in tips of fingers and toes, this can be temporary or permanent. ## Delayed side effects - Infertility is probably infrequent with ABVD. Several studies have suggested that, while sperm counts in men decrease during chemotherapy, they return to normal after completion of ABVD. In women, follicle-stimulating hormone levels remained normal while receiving ABVD, suggesting preserved ovarian function. Regardless of these data, fertility options (eg sperm banking) should be discussed with an oncologist before beginning ABVD therapy. - Pulmonary toxicity, or lung damage, can occur with the use of bleomycin in ABVD, especially when radiation therapy to the chest is also given as part of the treatment for Hodgkin's lymphoma. This toxicity develops months to years after completing chemotherapy, and usually manifests as cough and shortness of breath. Pulmonary function tests are often used to assess for bleomycin-related damage to the lungs. One study found bleomycin lung damage in 18% of patients receiving ABVD for Hodgkin's disease. Retrospective analyses have questioned whether bleomycin is necessary at all; however, at this point it remains a standard part of ABVD. - Cardiac toxicity, or cardiomyopathy, can be a late side effect of adriamycin. The occurrence of adriamycin-related cardiac toxicity is related to the total lifetime dose of adriamycin, and increases sharply in people who receive a cumulative dose of more than 400 mg/m2. Almost all patients treated with ABVD receive less than this dose (for 6 cycles of ABVD, the cumulative adriamycin dose is 300 mg/m2); therefore, adriamycin-related cardiac toxicity is very uncommon with ABVD. - Secondary malignancies. Patients cured of Hodgkin's lymphoma remain at increased risk of developing other (secondary) cancers. Treatment-related leukemias are uncommon with ABVD, especially as compared with MOPP. However, one study found a risk of second cancers as high as 28% at 25 years after treatment for Hodgkin's lymphoma, although most of the patients in this study were treated with MOPP chemotherapy rather than ABVD. Many of these second cancers were lung cancers or, in women, breast cancers, emphasizing the importance of smoking cessation and regular preventive care after completion of treatment. Radiation and chemotherapy probably both play a role in the development of these secondary malignancies; the exact contribution of chemotherapy such as ABVD can be difficult to tease out. # Supportive care Supportive care refers to efforts to prevent or treat side effects of ABVD chemotherapy, and to help patients get through the chemotherapy with the least possible discomfort. ## Antiemetics Significant advances in antiemetic, or anti-nausea, medications have been made in the beginning of the 21st century. Patients will often receive a combination of 5-HT3 receptor antagonists (e.g. ondansetron), corticosteroids, and benzodiazepines before chemotherapy to prevent nausea. These medicines are also effective after nausea develops, as are phenothiazines. Each person's sensitivity to nausea and vomiting varies. Overall, while patients often experience some mild to moderate nausea, severe nausea or vomiting are uncommon with ABVD. ## Growth factors Blood growth factors are medicines that stimulate the bone marrow to produce more of a certain kind of blood cell. Commonly used examples include G-CSF and erythropoietin. These drugs are sometimes used with ABVD to prevent neutropenia (low white blood cell count) and anemia related to the chemotherapy, although their use is not universal.	ABVD # Overview ABVD is a chemotherapy regimen used in the first-line treatment of Hodgkin's lymphoma. It consists of concurrent treatment with the chemotherapy drugs adriamycin, bleomycin, vinblastine and dacarbazine. # Indications As of 2006, ABVD is widely used as the initial chemotherapy treatment for newly diagnosed Hodgkin's lymphoma. The other chemotherapy regimen that is widely used in this setting is the Stanford V regimen. # History Prior to the mid-1960's, advanced-stage Hodgkin disease was treated with single-agent chemotherapy, with fairly dismal long-term survival and cure rates. With advances in the understanding of chemotherapy resistance and the development of combination chemotherapy, Vincent DeVita and George Canellos at the National Cancer Institute (United States) developed the MOPP regimen. This combination of mechlorethamine, vincristine (Oncovin), procarbazine, and prednisone proved capable of curing almost 70% of patients with advanced-stage Hodgkin's lymphoma.[1][2] While MOPP was remarkably successful in curing advanced Hodgkin's lymphoma, its toxicity remained significant. Aside from bone marrow suppression, frequent side effects included nerve injury caused by vincristine and allergic reactions to procarbazine. Long-term effects were also a concern, as patients were often cured and could expect long survival after chemotherapy. Infertility was a major long-term side effect, and even more seriously, the risk of developing treatment-related myelodysplasia or acute leukemia was increased up to 14-fold in patients who received MOPP.[3] These treatment-related hematological malignancies peaked at 5 to 9 years after treatment for Hodgkin's lymphoma, and were associated with a dismally poor prognosis. ## Development of ABVD Therefore, alternate regimens were tested in an attempt to avoid alkylating agents (such as mechlorethamine), which were thought to be responsible for many of the long-term side effects of MOPP. ABVD was developed as a potentially less toxic and more effective alternative to MOPP; initial results with ABVD were published in 1975 by an Italian group led by Bonadonna.[4] A number of trials then compared ABVD to previous regimens for Hodgkin's lymphoma. A large trial by CALGB suggested that ABVD was superior to MOPP, with a higher rate of overall response, less hematologic toxicity, better relapse-free survival, and better outcomes after relapse in the patients treated with ABVD.[5] Later studies confirmed the superiority of ABVD in terms of effectiveness, and also demonstrated that late side effects, such as treatment-related acute leukemia, were less common with ABVD as compared to MOPP.[6] Taken together, these results led ABVD to the replacement of MOPP with ABVD in the first-line treatment of Hodgkin's lymphoma. # Administration One cycle of ABVD chemotherapy is typically given over 4 weeks, with two doses in each cycle (on day 1 and day 15). All four of the chemotherapy drugs are given intravenously. ABVD chemotherapy is usually given in the outpatient setting — that is, it does not require hospitalization. Typical dosages for one 28-day cycle of ABVD are as follows - Adriamycin 25 mg/m2 IV on days 1 and 15 - Bleomycin 10 mg/m2 IV on days 1 and 15 - Vinblastine 6 mg/m2 IV on days 1 and 15 - Dacarbazine 375 mg/m2 IV on days 1 and 15 The total number of cycles given depends upon the stage of the disease and how well the patient tolerates chemotherapy. Doses may be delayed because of neutropenia, thrombocytopenia, or other side effects. # Side effects In the relative spectrum of cancer chemotherapy, ABVD is not a particularly toxic regimen. Side effects of ABVD can be divided into acute (those occurring while receiving chemotherapy) and delayed (those occurring months to years after completion of chemotherapy). Delayed side effects have assumed particular importance because many patients treated for Hodgkin's lymphoma are cured and can expect long lives after completion of chemotherapy. ## Acute side effects - Hair loss, or alopecia, is a fairly common but not universal side effect of ABVD. Hair that is lost returns in the months after completion of chemotherapy. - Nausea and vomiting can occur with ABVD, although treatments for chemotherapy-induced nausea and vomiting have improved substantially (see Supportive care below). - Low blood counts, or myelosuppression, occur about 50% of the time with ABVD. Blood cell growth factors are sometimes used to prevent this (see Supportive care below). Blood counts are checked frequently while receiving chemotherapy. Any fever or sign of infection that develops needs to be promptly evaluated; severe infections can develop rapidly in a person with a low white blood cell count due to chemotherapy. - Allergic reactions to bleomycin can occur. A small test dose of bleomycin is often given prior to the first round of ABVD to screen for patients who may be allergic. - Neuropathy Numbness in tips of fingers and toes, this can be temporary or permanent. ## Delayed side effects - Infertility is probably infrequent with ABVD. Several studies have suggested that, while sperm counts in men decrease during chemotherapy, they return to normal after completion of ABVD.[6][7][8] In women, follicle-stimulating hormone levels remained normal while receiving ABVD, suggesting preserved ovarian function. Regardless of these data, fertility options (eg sperm banking) should be discussed with an oncologist before beginning ABVD therapy. - Pulmonary toxicity, or lung damage, can occur with the use of bleomycin in ABVD, especially when radiation therapy to the chest is also given as part of the treatment for Hodgkin's lymphoma. This toxicity develops months to years after completing chemotherapy, and usually manifests as cough and shortness of breath. Pulmonary function tests are often used to assess for bleomycin-related damage to the lungs. One study found bleomycin lung damage in 18% of patients receiving ABVD for Hodgkin's disease.[9] Retrospective analyses have questioned whether bleomycin is necessary at all;[10] however, at this point it remains a standard part of ABVD. - Cardiac toxicity, or cardiomyopathy, can be a late side effect of adriamycin. The occurrence of adriamycin-related cardiac toxicity is related to the total lifetime dose of adriamycin, and increases sharply in people who receive a cumulative dose of more than 400 mg/m2. Almost all patients treated with ABVD receive less than this dose (for 6 cycles of ABVD, the cumulative adriamycin dose is 300 mg/m2); therefore, adriamycin-related cardiac toxicity is very uncommon with ABVD. - Secondary malignancies. Patients cured of Hodgkin's lymphoma remain at increased risk of developing other (secondary) cancers. Treatment-related leukemias are uncommon with ABVD, especially as compared with MOPP.[6] However, one study found a risk of second cancers as high as 28% at 25 years after treatment for Hodgkin's lymphoma, although most of the patients in this study were treated with MOPP chemotherapy rather than ABVD.[11] Many of these second cancers were lung cancers or, in women, breast cancers, emphasizing the importance of smoking cessation and regular preventive care after completion of treatment. Radiation and chemotherapy probably both play a role in the development of these secondary malignancies; the exact contribution of chemotherapy such as ABVD can be difficult to tease out. # Supportive care Supportive care refers to efforts to prevent or treat side effects of ABVD chemotherapy, and to help patients get through the chemotherapy with the least possible discomfort. ## Antiemetics Significant advances in antiemetic, or anti-nausea, medications have been made in the beginning of the 21st century. Patients will often receive a combination of 5-HT3 receptor antagonists (e.g. ondansetron), corticosteroids, and benzodiazepines before chemotherapy to prevent nausea. These medicines are also effective after nausea develops, as are phenothiazines. Each person's sensitivity to nausea and vomiting varies. Overall, while patients often experience some mild to moderate nausea, severe nausea or vomiting are uncommon with ABVD. ## Growth factors Blood growth factors are medicines that stimulate the bone marrow to produce more of a certain kind of blood cell. Commonly used examples include G-CSF and erythropoietin. These drugs are sometimes used with ABVD to prevent neutropenia (low white blood cell count) and anemia related to the chemotherapy, although their use is not universal.	https://www.wikidoc.org/index.php/ABVD
ab805855d536f5f9d9ab50084859df17a7652299	wikidoc	ACHE	ACHE Acetylcholinesterase (Yt blood group), also known as AChE, is a human enzyme coded for by a gene. Acetylcholinesterase hydrolyzes the neurotransmitter acetylcholine at neuromuscular junctions and brain cholinergic synapses, and thus terminates signal transmission. It is also found on the red blood cell membranes, where it constitutes the Yt blood group antigen. Acetylcholinesterase exists in multiple molecular forms, which possess similar catalytic properties, but differ in their oligomeric assembly and mode of cell attachment to the cell surface. It is encoded by the single AChE gene; and the structural diversity in the gene products arises from alternative mRNA splicing and post-translational associations of catalytic and structural subunits. The major form of acetylcholinesterase found in brain, muscle, and other tissues is the hydrophilic species, which forms disulfide-linked oligomers with collagenous, or lipid-containing structural subunits. The other, alternatively-spliced form, expressed primarily in the erythroid tissues, differs at the C-terminal end, and contains a cleavable hydrophobic peptide with a GPI-anchor site. It associates with the membranes through the phosphoinositide (PI) moieties added post-translationally. Acetylcholinesterase is the target of nerve gases. The agents blocks the function of acetylcholinesterase and thus causes interminable muscle contraction throughout the body.	ACHE Acetylcholinesterase (Yt blood group), also known as AChE, is a human enzyme coded for by a gene. Acetylcholinesterase hydrolyzes the neurotransmitter acetylcholine at neuromuscular junctions and brain cholinergic synapses, and thus terminates signal transmission. It is also found on the red blood cell membranes, where it constitutes the Yt blood group antigen. Acetylcholinesterase exists in multiple molecular forms, which possess similar catalytic properties, but differ in their oligomeric assembly and mode of cell attachment to the cell surface. It is encoded by the single AChE gene; and the structural diversity in the gene products arises from alternative mRNA splicing and post-translational associations of catalytic and structural subunits. The major form of acetylcholinesterase found in brain, muscle, and other tissues is the hydrophilic species, which forms disulfide-linked oligomers with collagenous, or lipid-containing structural subunits. The other, alternatively-spliced form, expressed primarily in the erythroid tissues, differs at the C-terminal end, and contains a cleavable hydrophobic peptide with a GPI-anchor site. It associates with the membranes through the phosphoinositide (PI) moieties added post-translationally.[1] Acetylcholinesterase is the target of nerve gases. The agents blocks the function of acetylcholinesterase and thus causes interminable muscle contraction throughout the body.	https://www.wikidoc.org/index.php/ACHE
1a31c3de476528b242e3da6852b2c2d894f674d5	wikidoc	ACO2	ACO2 Aconitase 2, mitochondrial is a protein that in humans is encoded by the ACO2 gene. # Structure The secondary structure of ACO2 consists of numerous alternating alpha helices and beta sheets (SCOP classification: α/β alternating). The tertiary structure reveals that the active site is buried in the middle of the enzyme, and, since there is only one subunit, there is no quaternary structure. Aconitase consists of four domains: three of the domains are tightly compact, and the fourth domain is more flexible, allowing for conformational changes. The ACO2 protein contains a 4Fe-4S iron-sulfur cluster. This iron sulfur cluster does not have the typical function of participating in oxidation-reduction reactions, but rather facilitates the elimination of the citrate hydroxyl group by holding the group in a certain conformation and orientation. It is at this 4Fe-4S site that citrate or isocitrate binds to initiate catalysis. The rest of the active site is made up of the following residues: Gln72, Asp100, His101, Asp165, Ser166, His167, His147, Glu262, Asn258, Cys358, Cys421, Cys424, Cys358, Cys421, Asn446, Arg447, Arg452, Asp568, Ser642, Ser643, Arg644, Arg580. Their functions have yet to be elucidated. # Function The protein encoded by this gene belongs to the aconitase/IPM isomerase family. It is an enzyme that catalyzes the interconversion of citrate to isocitrate via cis-aconitate in the second step of the TCA cycle. This protein is encoded in the nucleus and functions in the mitochondrion. It was found to be one of the mitochondrial matrix proteins that are preferentially degraded by the serine protease 15 (PRSS15), also known as Lon protease, after oxidative modification. ## Mechanism While both forms of aconitases have similar functions, most studies focus on ACO2. The iron-sulfur (4Fe-4S) cofactor is held in place by the sulfur atoms on Cys385, Cys448, and Cys451, which are bind to three of the four available iron atoms. A fourth iron atom is included in the cluster together with a water molecule when the enzyme is activated. This fourth iron atom binds to either one, two, or three partners; in this reaction, oxygen atoms belonging to outside metabolites are always involved. When ACO2 is not bound to a substrate, the iron-sulfur cluster is bound to a hydroxyl group through an interaction with one of the iron molecules. When the substrate binds, the bound hydroxyl becomes protonated. A hydrogen bond forms between His101 and the protonated hydroxyl, which allows the hydroxyl to form a water molecule. Alternatively, the proton could be donated by His167 as this histidine is hydrogen bonded to a H2O molecule. His167 is also hydrogen bonded to the bound H2O in the cluster. Both His101 and His167 are paired with carboxylates Asp100 and Glu262, respectively, and are likely to be protonated. The conformational change associated with substrate binding reorients the cluster. The residue that removes a proton from citrate or isocitrate is Ser642. This causes the cis-Aconitate intermediate, which is a direct result of the deprotonation. Then, there is a rehydration of the double bond of cis-aconitate to form the product. # Clinical significance A serious ailment associated with aconitase is known as aconitase deficiency. It is caused by a mutation in the gene for iron-sulfur cluster scaffold protein (ISCU), which helps build the Fe-S cluster on which the activity of aconitase depends. The main symptoms are myopathy and exercise intolerance; physical strain is lethal for some patients because it can lead to circulatory shock. There are no known treatments for aconitase deficiency. Another disease associated with aconitase is Friedreich's ataxia (FRDA), which is caused when the Fe-S proteins in aconitase and succinate dehydrogenase have decreased activity. A proposed mechanism for this connection is that decreased Fe-S activity in aconitase and succinate dehydrogenase is correlated with excess iron concentration in the mitochondria and insufficient iron in the cytoplasm, disrupting iron homeostasis. This deviance from homeostasis causes FRDA, a neurodegenerative disease for which no effective treatments have been found. Finally, aconitase is thought to be associated with diabetes. Although the exact connection is still being determined, multiple theories exist. In a study of organs from mice with alloxan diabetes (experimentally induced diabetes) and genetic diabetes, lower aconitase activity was found to decrease the rates of metabolic reactions involving citrate, pyruvate, and malate. In addition, citrate concentration was observed to be unusually high. Since these abnormal data were found in diabetic mice, the study concluded that low aconitase activity is likely correlated with genetic and alloxan diabetes. Another theory is that, in diabetic hearts, accelerated phosphorylation of heart aconitase by protein kinase C causes aconitase to speed up the final step of its reverse reaction relative to its forward reaction. That is, it converts isocitrate back to cis-aconitate more rapidly than usual, but the forward reaction proceeds at the usual rate. This imbalance may contribute to disrupted metabolism in diabetics. The mitochondrial form of aconitase, ACO2, is correlated with many diseases, as it is directly involved in the conversion of glucose into ATP, or the central metabolic pathway. Decreased expression of ACO2 in gastric cancer cells has been associated with a poor prognosis; this effect has also been seen in prostate cancer cells. A few treatments have been identified in vitro to induce greater ACO2 expression, including exposing the cells to hypoxia and the element manganese.	ACO2 Aconitase 2, mitochondrial is a protein that in humans is encoded by the ACO2 gene.[1] # Structure The secondary structure of ACO2 consists of numerous alternating alpha helices and beta sheets (SCOP classification: α/β alternating). The tertiary structure reveals that the active site is buried in the middle of the enzyme, and, since there is only one subunit, there is no quaternary structure. Aconitase consists of four domains: three of the domains are tightly compact, and the fourth domain is more flexible, allowing for conformational changes.[2] The ACO2 protein contains a 4Fe-4S iron-sulfur cluster. This iron sulfur cluster does not have the typical function of participating in oxidation-reduction reactions, but rather facilitates the elimination of the citrate hydroxyl group by holding the group in a certain conformation and orientation.[3] It is at this 4Fe-4S site that citrate or isocitrate binds to initiate catalysis. The rest of the active site is made up of the following residues: Gln72, Asp100, His101, Asp165, Ser166, His167, His147, Glu262, Asn258, Cys358, Cys421, Cys424, Cys358, Cys421, Asn446, Arg447, Arg452, Asp568, Ser642, Ser643, Arg644, Arg580. Their functions have yet to be elucidated.[4] # Function The protein encoded by this gene belongs to the aconitase/IPM isomerase family. It is an enzyme that catalyzes the interconversion of citrate to isocitrate via cis-aconitate in the second step of the TCA cycle. This protein is encoded in the nucleus and functions in the mitochondrion. It was found to be one of the mitochondrial matrix proteins that are preferentially degraded by the serine protease 15 (PRSS15), also known as Lon protease, after oxidative modification. ## Mechanism While both forms of aconitases have similar functions, most studies focus on ACO2. The iron-sulfur (4Fe-4S) cofactor is held in place by the sulfur atoms on Cys385, Cys448, and Cys451, which are bind to three of the four available iron atoms. A fourth iron atom is included in the cluster together with a water molecule when the enzyme is activated. This fourth iron atom binds to either one, two, or three partners; in this reaction, oxygen atoms belonging to outside metabolites are always involved.[4] When ACO2 is not bound to a substrate, the iron-sulfur cluster is bound to a hydroxyl group through an interaction with one of the iron molecules. When the substrate binds, the bound hydroxyl becomes protonated. A hydrogen bond forms between His101 and the protonated hydroxyl, which allows the hydroxyl to form a water molecule. Alternatively, the proton could be donated by His167 as this histidine is hydrogen bonded to a H2O molecule. His167 is also hydrogen bonded to the bound H2O in the cluster. Both His101 and His167 are paired with carboxylates Asp100 and Glu262, respectively, and are likely to be protonated. The conformational change associated with substrate binding reorients the cluster. The residue that removes a proton from citrate or isocitrate is Ser642. This causes the cis-Aconitate intermediate, which is a direct result of the deprotonation. Then, there is a rehydration of the double bond of cis-aconitate to form the product.[5] # Clinical significance A serious ailment associated with aconitase is known as aconitase deficiency.[6] It is caused by a mutation in the gene for iron-sulfur cluster scaffold protein (ISCU), which helps build the Fe-S cluster on which the activity of aconitase depends.[6] The main symptoms are myopathy and exercise intolerance; physical strain is lethal for some patients because it can lead to circulatory shock.[6][7] There are no known treatments for aconitase deficiency.[6] Another disease associated with aconitase is Friedreich's ataxia (FRDA), which is caused when the Fe-S proteins in aconitase and succinate dehydrogenase have decreased activity.[8] A proposed mechanism for this connection is that decreased Fe-S activity in aconitase and succinate dehydrogenase is correlated with excess iron concentration in the mitochondria and insufficient iron in the cytoplasm, disrupting iron homeostasis.[8] This deviance from homeostasis causes FRDA, a neurodegenerative disease for which no effective treatments have been found.[8] Finally, aconitase is thought to be associated with diabetes.[9][10] Although the exact connection is still being determined, multiple theories exist.[9][10] In a study of organs from mice with alloxan diabetes (experimentally induced diabetes[11]) and genetic diabetes, lower aconitase activity was found to decrease the rates of metabolic reactions involving citrate, pyruvate, and malate.[9] In addition, citrate concentration was observed to be unusually high.[9] Since these abnormal data were found in diabetic mice, the study concluded that low aconitase activity is likely correlated with genetic and alloxan diabetes.[9] Another theory is that, in diabetic hearts, accelerated phosphorylation of heart aconitase by protein kinase C causes aconitase to speed up the final step of its reverse reaction relative to its forward reaction.[10] That is, it converts isocitrate back to cis-aconitate more rapidly than usual, but the forward reaction proceeds at the usual rate.[10] This imbalance may contribute to disrupted metabolism in diabetics.[10] The mitochondrial form of aconitase, ACO2, is correlated with many diseases, as it is directly involved in the conversion of glucose into ATP, or the central metabolic pathway. Decreased expression of ACO2 in gastric cancer cells has been associated with a poor prognosis;[12] this effect has also been seen in prostate cancer cells.[13][14] A few treatments have been identified in vitro to induce greater ACO2 expression, including exposing the cells to hypoxia and the element manganese.[15][16]	https://www.wikidoc.org/index.php/ACO2

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