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0d124dabbd6399660a64f2b91eb4fb2195bc40c7	wikidoc	FOXRED1	FOXRED1 FAD-dependent oxidoreductase domain-containing protein 1 (FOXRED1), also known as H17, or FP634 is an enzyme that in humans is encoded by the FOXRED1 gene. FOXRED1 is an oxidoreductase and complex I-specific molecular chaperone involved in the assembly and stabilization of NADH dehydrogenase (ubiquinone) also known as complex I, which is located in the mitochondrial inner membrane and is the largest of the five complexes of the electron transport chain. Mutations in FOXRED1 have been associated with Leigh syndrome and infantile-onset mitochondrial encephalopathy. # Structure FOXRED1 is located on the q arm of chromosome 11 in position 14.2 and has 12 exons. The FOXRED1 gene produces a 53.8 kDa protein composed of 486 amino acids. Alternatively spliced transcript variants have been observed for this gene. FOXRED1 contains an oxidoreductase FAD-binding domain and is homologous to FAD-binding proteins dimethylglycine dehydrogenase, sarcosine dehydrogenase, L-pipecolic acid oxidase, peroxisomal sarcosine oxidase, and pyrvuvate dehydrogenase regulatory subunit. FOXRED1's structural similarities to sarcosine oxidase (MSOX) predict that tyrosine residues Y410 and Y411 make up the site of covalent attachment of FAD. Additionally, a phenyl moiety at p. 359 is thought to be critical for function. Finally, FOXRED1 is a matrix-directed protein that is thought to be imported through the presence of a mitochondrial membrane potential rather than through a cleavable targeting signal. However, others suggest that it contains a 23 amino acid N-terminal mitochondrial localization sequence and that this sequence is cleaved upon entry to form the mature protein. # Function The FOXRED1 gene encodes an enzyme that is localized in the mitochondria and which helps in the assembly and stabilization of NADH:ubiquinone oxidoreductase, a large multi-subunit enzyme in the mitochondrial respiratory chain. NADH:ubiquinone oxidoreductase (complex I) is involved in several physiological activities in the cell, including metabolite transport and ATP synthesis. Complex I catalyzes the transfer of electrons from NADH to ubiquinone (coenzyme Q) in the first step of the mitochondrial respiratory chain, resulting in the translocation of protons across the inner mitochondrial membrane. The encoded protein of FOXRED1 is an oxidoreductase and complex I-specific molecular chaperone. It plays a role in the mid-to-late stages of complex I intermediate assembly and is important for the assembly, stabilization, and function of complex I. It is proposed that FOXRED1 functions in a complex with core subunit NDUFS3 as well as accessory subunits NDUFA5, NDUFA10, NDUFB10 and NDUFS5. # Clinical Significance Mutations in FOXRED1 can result in mitochondrial deficiencies and associated disorders. A disorder of the mitochondrial respiratory chain can cause a wide range of clinical manifestations from lethal neonatal disease to adult-onset neurodegenerative disorders. Phenotypes include macrocephaly with progressive leukodystrophy, non-specific encephalopathy, cardiomyopathy, myopathy, liver disease, Leigh syndrome, Leber hereditary optic neuropathy, and some forms of Parkinson disease. Pathogenic mutations of FOXRED1 have included c.1054C>T; p.R352W, c.694C>T; p.Q232X, and c.1289A>G; p.N430S. Symptoms due to these mutations have included lactic acidosis, hypertrophic cardiomyopathy, and optic atrophy. Clinically, these variants have been associated with Leigh syndrome and infantile-onset mitochondrial encephalopathy. Survival with FOXRED1 mutations appears to be more common than in other complex I deficiencies and overexpression of mutant forms can lead to rescued complex I activity indicating that FOXRED1 activity can be compensated for to some degree. # Interactions FOXRED1 co-immunoprecipitates with complex I subunits NDUFB10, NDUFS5, NDUFA10, NDUFA8, NDUFS3 and NDUFA5 and may be associated with import machinery Tom20, Tom22 and MPP as well as chaperones mtHsp70, Hsp60, and Hsp10. In addition to co-complexes and potential associations, FOXRED1 has been confirmed to have protein-protein interactions with EXOSC10.	FOXRED1 FAD-dependent oxidoreductase domain-containing protein 1 (FOXRED1), also known as H17, or FP634 is an enzyme that in humans is encoded by the FOXRED1 gene.[1][2] FOXRED1 is an oxidoreductase and complex I-specific molecular chaperone involved in the assembly and stabilization of NADH dehydrogenase (ubiquinone) also known as complex I, which is located in the mitochondrial inner membrane and is the largest of the five complexes of the electron transport chain.[3][4][5] Mutations in FOXRED1 have been associated with Leigh syndrome[6][7] and infantile-onset mitochondrial encephalopathy.[4] # Structure FOXRED1 is located on the q arm of chromosome 11 in position 14.2 and has 12 exons.[1] The FOXRED1 gene produces a 53.8 kDa protein composed of 486 amino acids.[8][9] Alternatively spliced transcript variants have been observed for this gene.[1] FOXRED1 contains an oxidoreductase FAD-binding domain and is homologous to FAD-binding proteins dimethylglycine dehydrogenase, sarcosine dehydrogenase, L-pipecolic acid oxidase, peroxisomal sarcosine oxidase, and pyrvuvate dehydrogenase regulatory subunit. FOXRED1's structural similarities to sarcosine oxidase (MSOX) predict that tyrosine residues Y410 and Y411 make up the site of covalent attachment of FAD. Additionally, a phenyl moiety at p. 359 is thought to be critical for function.[4][6] Finally, FOXRED1 is a matrix-directed protein that is thought to be imported through the presence of a mitochondrial membrane potential rather than through a cleavable targeting signal.[6] However, others suggest that it contains a 23 amino acid N-terminal mitochondrial localization sequence and that this sequence is cleaved upon entry to form the mature protein.[4] # Function The FOXRED1 gene encodes an enzyme that is localized in the mitochondria and which helps in the assembly and stabilization of NADH:ubiquinone oxidoreductase, a large multi-subunit enzyme in the mitochondrial respiratory chain.[1][6] NADH:ubiquinone oxidoreductase (complex I) is involved in several physiological activities in the cell, including metabolite transport and ATP synthesis. Complex I catalyzes the transfer of electrons from NADH to ubiquinone (coenzyme Q) in the first step of the mitochondrial respiratory chain, resulting in the translocation of protons across the inner mitochondrial membrane.[10] The encoded protein of FOXRED1 is an oxidoreductase and complex I-specific molecular chaperone. It plays a role in the mid-to-late stages of complex I intermediate assembly and is important for the assembly, stabilization, and function of complex I. It is proposed that FOXRED1 functions in a complex with core subunit NDUFS3 as well as accessory subunits NDUFA5, NDUFA10, NDUFB10 and NDUFS5.[6] # Clinical Significance Mutations in FOXRED1 can result in mitochondrial deficiencies and associated disorders. A disorder of the mitochondrial respiratory chain can cause a wide range of clinical manifestations from lethal neonatal disease to adult-onset neurodegenerative disorders. Phenotypes include macrocephaly with progressive leukodystrophy, non-specific encephalopathy, cardiomyopathy, myopathy, liver disease, Leigh syndrome, Leber hereditary optic neuropathy, and some forms of Parkinson disease.[5] Pathogenic mutations of FOXRED1 have included c.1054C>T; p.R352W, c.694C>T; p.Q232X, and c.1289A>G; p.N430S. Symptoms due to these mutations have included lactic acidosis, hypertrophic cardiomyopathy, and optic atrophy. Clinically, these variants have been associated with Leigh syndrome[6][7] and infantile-onset mitochondrial encephalopathy.[4] Survival with FOXRED1 mutations appears to be more common than in other complex I deficiencies and overexpression of mutant forms can lead to rescued complex I activity indicating that FOXRED1 activity can be compensated for to some degree.[6] # Interactions FOXRED1 co-immunoprecipitates with complex I subunits NDUFB10, NDUFS5, NDUFA10, NDUFA8, NDUFS3 and NDUFA5 and may be associated with import machinery Tom20, Tom22 and MPP as well as chaperones mtHsp70, Hsp60, and Hsp10.[6] In addition to co-complexes and potential associations, FOXRED1 has been confirmed to have protein-protein interactions with EXOSC10.[11]	https://www.wikidoc.org/index.php/FOXRED1
e64d0225a698291a481e7a2ff0dd790c9caa0bba	wikidoc	Neuroma	Neuroma Synonyms and keywords: Traumatic neuroma; Morton neuroma; Amputation neuroma; Pseudoneuroma; Morton’s metatarsalgia; Plantar interdigital neuroma; Morton's intermetatarsal neuroma; Morton's entrapment; Morton's disease; Morton's neuropathy; Morton's neuralgia; Intermetatarsal neuroma; Intermetatarsal space neuroma; Intermetatarsal nerve entrapment; Interdigital neuroma; Interdigital nerve compression; Interdigital nerve enlargement; Joplin's neuroma; Plantar neuroma; Scar neuroma; Terminal neuroma; Stump neuroma # Overview Neuroma (Neuro- is from the Greek for nerve) is defined as a benign tumor of a nerve. However, neuroma commonly refers to any tumor of cells of the nervous system. Neuromas form part of the peripheral nerve sheath tumors and belong to Reactive class of tumors. Neuroma was first described by Thomas Morton in 1876. Neuromas may be classified according to histopathological features into 3 groups: Morton's neuroma, traumatic neuroma, and neoplasic neuromas. The pathogenesis of neuroma is characterized by neural degeneration with epineural and endoneural vascular hyalinization, and perineural fibrosis. Neuroma is more commonly observed among patients aged between 15 to 50 years old. Neuroma is more commonly observed among middle aged adults. Females are more commonly affected with neuroma than males. The female to male ratio is approximately 5:1. Common risk factors in the development of neuroma include improper footwear and high impact sports (e.g., rock-climbing, ballet dancing). A major complication of neuroma is chronic neuropathic pain. On ultrasound, neuroma is characterized as a well-defined, hypoechoic lesion located in the intermetatarsal space proximal to the metatarsal head. Patients with neuroma usually appear with antalgic posture. Physical examination may be remarkable for tenderness to palpation and dysesthetic pain. Surgical excision is the treatment of choice for patients with neuroma; this surgical intervention is associated with a relatively favorable success rate, approximately 80%. The recurrence rate after surgery is as high as 50%. # Historical Perspective - The term neuroma originates from the following two Greek words: neuro- from the Greek word for nerve (νεῦρον) -oma (-ωμα) from the Greek word for swelling - neuro- from the Greek word for nerve (νεῦρον) - -oma (-ωμα) from the Greek word for swelling - In 1876, Neuroma was first described by Thomas Morton # Classification - Neuroma may be classified according to histopathological features into following groups: # Pathophysiology - The pathogenesis of neuroma is characterized by neural degeneration with epineural and endoneural vascular hyalinization, and perineural fibrosis - The pathogenesis of traumatic neuroma is characterized by: Tangle of neural fibers and connective tissue that develops following a peripheral nerve injury Interruption in continuity of nerve causing wallerian degeneration (loss of axons in proximal stump and retraction of axons in distal segment), followed by exuberant regeneration of nerve and formation of mass of Schwann cells, axons and fibrous cells Chronic reactive fibroinflammatory disorganized regeneration around a nerve after an injury (such as traction injury or chronic repetitive stress) - Tangle of neural fibers and connective tissue that develops following a peripheral nerve injury - Interruption in continuity of nerve causing wallerian degeneration (loss of axons in proximal stump and retraction of axons in distal segment), followed by exuberant regeneration of nerve and formation of mass of Schwann cells, axons and fibrous cells - Chronic reactive fibroinflammatory disorganized regeneration around a nerve after an injury (such as traction injury or chronic repetitive stress) - Morton's neuroma is characterized by being located in the 3rd web-space, between 3rd and 4th metatarsal heads, or sometimes in the second or fourth interspaces - Another subtype of traumatic neuroma is terminal neuroma (also known as "stump neuroma") which can occur after transection of the nerve (e.g. limb amputation) - There are no genetic mutations associated with the development of neuroma - On gross pathology, characteristic findings of neuroma, includes: Adherent fibrofatty tissue Small, firm, oval, yellowish-white, slowly growing, palpable nodule on skin (no discoloration of skin on the top of nodule) </=2cm in size - Adherent fibrofatty tissue - Small, firm, oval, yellowish-white, slowly growing, palpable nodule on skin (no discoloration of skin on the top of nodule) - </=2cm in size - On microscopic histopathological analysis, characteristic findings of neuroma, include: Extensive fibrosis around and within the nerve Digital artery Thrombosis Arterial thickening - Extensive fibrosis around and within the nerve - Digital artery - Thrombosis - Arterial thickening ## Histopathology of traumatic neuroma - Numerous well formed small nerve twigs - Limited soft tissue infiltration - Contains axons in haphazardly arranged nerves within mature collagenous scar with entrapped smooth muscle ## Common sites of involvement by traumatic neuroma - Most common oral locations are: Tongue Near mental foramen of mouth - Tongue - Near mental foramen of mouth - Rarely involves: Head Neck - Head - Neck # Causes - Common causes of neuroma include: Indirect nerve trauma Especially during a surgery Cone biopsy (rare complication) 55% of hysterectomy patients have microneuromas, associated with childbirth Traction injury Chronic repetitive stress - Indirect nerve trauma Especially during a surgery Cone biopsy (rare complication) 55% of hysterectomy patients have microneuromas, associated with childbirth Traction injury Chronic repetitive stress - Especially during a surgery - Cone biopsy (rare complication) - 55% of hysterectomy patients have microneuromas, associated with childbirth - Traction injury - Chronic repetitive stress - Morton's neuroma is associated with: Wearing tight shoes and high heels Overpronation Abnormal positioning of toes Flat feet Forefoot problems such as: Bunions Hammer toes High foot arches - Wearing tight shoes and high heels - Overpronation - Abnormal positioning of toes - Flat feet - Forefoot problems such as: Bunions Hammer toes - Bunions - Hammer toes - High foot arches # Epidemiology and Demographics - Neuroma is an uncommon disease ## Age - Neuroma is more commonly observed among patients aged between 15 to 50 years old - Neuroma is more commonly observed among middle aged adults ## Gender - Females are more commonly affected with neuroma than males - The female to male ratio is approximately 5:1 ## Race - There is no racial predilection for neuroma # Risk Factors - Common risk factors in the development of neuroma include: Improper footwear/tight shoes High-impact sports (e.g., rock-climbing, ballet dancing, jogging, running, snow skiing) Overpronation - Improper footwear/tight shoes - High-impact sports (e.g., rock-climbing, ballet dancing, jogging, running, snow skiing) - Overpronation # Natural History, Complications and Prognosis - The majority of patients with neuroma are symptomatic at the time of diagnosis - Early clinical features include neuropathic pain or local tenderness - If left untreated, the majority of patients with neuroma may progress to develop difficulty walking and limping - A significant complication of neuroma is chronic neuropathic pain - Prognosis is generally good, and the survival rate of patients with neuroma is 99% # Diagnosis ## Symptoms - Neuroma is usually asymptomatic - Symptoms of neuroma may include: Focal area of traumatic neuropathic pain radiating to toes, with the presence of a typical trigger point in the area of a neuroma (especially with the pressure application) causing the patient to feel: Shooting Burning Stabbing Raw Gnawing Sickening sensations Numbness Paresthesia over the injured area Dysesthesia (painful hypersensitivity to normal light tactile stimuli) Functional impairment Psychological distress (severely decreasing the quality of life) - Focal area of traumatic neuropathic pain radiating to toes, with the presence of a typical trigger point in the area of a neuroma (especially with the pressure application) causing the patient to feel: Shooting Burning Stabbing Raw Gnawing Sickening sensations - Shooting - Burning - Stabbing - Raw - Gnawing - Sickening sensations - Numbness - Paresthesia over the injured area - Dysesthesia (painful hypersensitivity to normal light tactile stimuli) - Functional impairment - Psychological distress (severely decreasing the quality of life) ## Physical Examination - Patients with neuroma usually appear with antalgic posture - Physical examination may be remarkable for: Tenderness to palpation Limitation of range of motion Dysesthetic pain Mulder's sign: Replication of symptoms or clicking sensations upon direct pressure between the metatarsal heads or compression of transverse arch in forefoot between the finger and thumb - Tenderness to palpation - Limitation of range of motion - Dysesthetic pain - Mulder's sign: Replication of symptoms or clicking sensations upon direct pressure between the metatarsal heads or compression of transverse arch in forefoot between the finger and thumb - Replication of symptoms or clicking sensations upon direct pressure between the metatarsal heads or compression of transverse arch in forefoot between the finger and thumb ## Laboratory Findings - There are no specific laboratory findings associated with neuroma ## Imaging Findings ### MRI - On MRI, characteristic findings of neuroma include: Dumbbell/ovoid-shaped lesion at a similar position to that described on ultrasound T1: typically low-to-iso signal T2: typically low signal but can sometimes be intermediate in signal T1 C+ (Gd): tends to show intense enhancement - Dumbbell/ovoid-shaped lesion at a similar position to that described on ultrasound - T1: typically low-to-iso signal - T2: typically low signal but can sometimes be intermediate in signal - T1 C+ (Gd): tends to show intense enhancement - On MRI, characteristic findings of traumatic neuroma include: Fusiform swelling of a nerve or a bulbous mass at a nerve end The parent nerve of some small nerve may difficult or impossible to discern T2/STIR: inhomogeneous hyperintensity (may have a hypointense rim) T1 C+ (Gd): variable contrast enhancement - Fusiform swelling of a nerve or a bulbous mass at a nerve end - The parent nerve of some small nerve may difficult or impossible to discern - T2/STIR: inhomogeneous hyperintensity (may have a hypointense rim) - T1 C+ (Gd): variable contrast enhancement ### Ultrasound - Ultrasound can help distinguish neuroma from: Intermetatarsal bursal swelling or Synovitis in adjacent joints - Intermetatarsal bursal swelling or - Synovitis in adjacent joints - On ultrasound, neuroma is characterized by the following findings: Round to ovoid Well-defined, hypoechoic lesion Located in the intermetatarsal space proximal to the metatarsal head - Round to ovoid - Well-defined, hypoechoic lesion - Located in the intermetatarsal space proximal to the metatarsal head - On ultrasound, traumatic neuroma is characterized by the following findings: Swollen nerve (mass-like) Hypoechoic Loss of normal fibrillar pattern Usually small, but may be as large as 5 cm - Swollen nerve (mass-like) - Hypoechoic - Loss of normal fibrillar pattern - Usually small, but may be as large as 5 cm # Treatment ## Medical Therapy ### Conservative therapy for Morton's neuroma - Morton's neuroma should be managed conservatively before proceeding to expensive diagnostic procedures - Conservative measures for pain relief include: Decreasing pressure on the metatarsal heads by using: Metatarsal support Metatarsal bars Padding techniques (it's important to place inserts properly just proximal to the metatarsal head), such as: Metatarsal pads Toe crest pads Tapping the toe area Shoe inserts (orthotics) help in correcting any mechanical imbalance in the foot Specialized orthopedic shoes Comfortable shoes (with the help of a professional shoe fitting device) having: Wider toe box allowing spread of metatarsal heads Low heels Good arch support Physical therapy Ice massage Strength exercises for intrinsic foot muscles Resting - Decreasing pressure on the metatarsal heads by using: Metatarsal support Metatarsal bars Padding techniques (it's important to place inserts properly just proximal to the metatarsal head), such as: Metatarsal pads Toe crest pads Tapping the toe area Shoe inserts (orthotics) help in correcting any mechanical imbalance in the foot Specialized orthopedic shoes Comfortable shoes (with the help of a professional shoe fitting device) having: Wider toe box allowing spread of metatarsal heads Low heels Good arch support - Metatarsal support - Metatarsal bars - Padding techniques (it's important to place inserts properly just proximal to the metatarsal head), such as: Metatarsal pads Toe crest pads - Metatarsal pads - Toe crest pads - Tapping the toe area - Shoe inserts (orthotics) help in correcting any mechanical imbalance in the foot - Specialized orthopedic shoes - Comfortable shoes (with the help of a professional shoe fitting device) having: Wider toe box allowing spread of metatarsal heads Low heels Good arch support - Wider toe box allowing spread of metatarsal heads - Low heels - Good arch support - Physical therapy - Ice massage - Strength exercises for intrinsic foot muscles - Resting ### Non-conservative medical therapy - When conservative measures fail, following medical therapy is used for non-surgical treatment of neuroma: Tricyclic antidepressants Anticonvulsants (more effective) Serotonin-norepinephrine reuptake inhibitors Ultrasound-guided interdigital injection of following nerve blocking agents via dorsal approach into the site of tenderness: Steroid Local anaesthetic Anti-inflammatory drugs (orally or injected into the toe area), such as: Ibuprofen (Advil, Motrin) Naproxen (Aleve, Naprosyn) Painkillers (not recommended for long-term treatment) - Tricyclic antidepressants - Anticonvulsants (more effective) - Serotonin-norepinephrine reuptake inhibitors - Ultrasound-guided interdigital injection of following nerve blocking agents via dorsal approach into the site of tenderness: Steroid Local anaesthetic - Steroid - Local anaesthetic - Anti-inflammatory drugs (orally or injected into the toe area), such as: Ibuprofen (Advil, Motrin) Naproxen (Aleve, Naprosyn) - Ibuprofen (Advil, Motrin) - Naproxen (Aleve, Naprosyn) - Painkillers (not recommended for long-term treatment) ## Surgery - Surgical excision is the treatment of choice for neuroma - Surgical excision is associated with a relatively favorable success rate of approximately 80% - Recurrence rate after surgery is as high as 50% ## Prevention - There are no primary preventive measures available for neuroma - Secondary prevention measures include: personal hygiene measures, such as wearing ergonomic shoes # Differential Diagnosis - Neuroma must be differentiated from other diseases that cause forefoot pain and numbness such as: Stress fracture (neck of the metatarsal) Rheumatoid arthritis Hammer toe Neurofibroma - Stress fracture (neck of the metatarsal) - Rheumatoid arthritis - Hammer toe - Neurofibroma	Neuroma Editor-In-Chief: C. Michael Gibson, M.S., M.D. [7]; Associate Editor(s)-in-Chief: Sara Mohsin, M.D.[8], Maria Fernanda Villarreal, M.D. [9] Synonyms and keywords: Traumatic neuroma; Morton neuroma; Amputation neuroma; Pseudoneuroma; Morton’s metatarsalgia; Plantar interdigital neuroma; Morton's intermetatarsal neuroma; Morton's entrapment; Morton's disease; Morton's neuropathy; Morton's neuralgia; Intermetatarsal neuroma; Intermetatarsal space neuroma; Intermetatarsal nerve entrapment; Interdigital neuroma; Interdigital nerve compression; Interdigital nerve enlargement; Joplin's neuroma; Plantar neuroma; Scar neuroma; Terminal neuroma; Stump neuroma # Overview Neuroma (Neuro- is from the Greek for nerve) is defined as a benign tumor of a nerve. However, neuroma commonly refers to any tumor of cells of the nervous system. Neuromas form part of the peripheral nerve sheath tumors and belong to Reactive class of tumors. Neuroma was first described by Thomas Morton in 1876. Neuromas may be classified according to histopathological features into 3 groups: Morton's neuroma, traumatic neuroma, and neoplasic neuromas. The pathogenesis of neuroma is characterized by neural degeneration with epineural and endoneural vascular hyalinization, and perineural fibrosis. Neuroma is more commonly observed among patients aged between 15 to 50 years old. Neuroma is more commonly observed among middle aged adults. Females are more commonly affected with neuroma than males. The female to male ratio is approximately 5:1. Common risk factors in the development of neuroma include improper footwear and high impact sports (e.g., rock-climbing, ballet dancing). A major complication of neuroma is chronic neuropathic pain. On ultrasound, neuroma is characterized as a well-defined, hypoechoic lesion located in the intermetatarsal space proximal to the metatarsal head. Patients with neuroma usually appear with antalgic posture. Physical examination may be remarkable for tenderness to palpation and dysesthetic pain. Surgical excision is the treatment of choice for patients with neuroma; this surgical intervention is associated with a relatively favorable success rate, approximately 80%. The recurrence rate after surgery is as high as 50%. # Historical Perspective - The term neuroma originates from the following two Greek words: neuro- from the Greek word for nerve (νεῦρον) -oma (-ωμα) from the Greek word for swelling - neuro- from the Greek word for nerve (νεῦρον) - -oma (-ωμα) from the Greek word for swelling - In 1876, Neuroma was first described by Thomas Morton # Classification - Neuroma may be classified according to histopathological features into following groups:[1][2][3][4] # Pathophysiology - The pathogenesis of neuroma is characterized by neural degeneration with epineural and endoneural vascular hyalinization, and perineural fibrosis[1] - The pathogenesis of traumatic neuroma is characterized by:[34][18][35] Tangle of neural fibers and connective tissue that develops following a peripheral nerve injury Interruption in continuity of nerve causing wallerian degeneration (loss of axons in proximal stump and retraction of axons in distal segment), followed by exuberant regeneration of nerve and formation of mass of Schwann cells, axons and fibrous cells Chronic reactive fibroinflammatory disorganized regeneration around a nerve after an injury (such as traction injury or chronic repetitive stress) - Tangle of neural fibers and connective tissue that develops following a peripheral nerve injury - Interruption in continuity of nerve causing wallerian degeneration (loss of axons in proximal stump and retraction of axons in distal segment), followed by exuberant regeneration of nerve and formation of mass of Schwann cells, axons and fibrous cells - Chronic reactive fibroinflammatory disorganized regeneration around a nerve after an injury (such as traction injury or chronic repetitive stress) - Morton's neuroma is characterized by being located in the 3rd web-space, between 3rd and 4th metatarsal heads, or sometimes in the second or fourth interspaces - Another subtype of traumatic neuroma is terminal neuroma (also known as "stump neuroma") which can occur after transection of the nerve (e.g. limb amputation) - There are no genetic mutations associated with the development of neuroma - On gross pathology, characteristic findings of neuroma, includes:[36] [37][38] Adherent fibrofatty tissue Small, firm, oval, yellowish-white, slowly growing, palpable nodule on skin (no discoloration of skin on the top of nodule) </=2cm in size - Adherent fibrofatty tissue - Small, firm, oval, yellowish-white, slowly growing, palpable nodule on skin (no discoloration of skin on the top of nodule) - </=2cm in size - On microscopic histopathological analysis, characteristic findings of neuroma, include:[37][38] Extensive fibrosis around and within the nerve Digital artery Thrombosis Arterial thickening - Extensive fibrosis around and within the nerve - Digital artery - Thrombosis - Arterial thickening ## Histopathology of traumatic neuroma - Numerous well formed small nerve twigs - Limited soft tissue infiltration - Contains axons in haphazardly arranged nerves within mature collagenous scar with entrapped smooth muscle ## Common sites of involvement by traumatic neuroma - Most common oral locations are: Tongue Near mental foramen of mouth - Tongue - Near mental foramen of mouth - Rarely involves: Head Neck - Head - Neck # Causes - Common causes of neuroma include:[37][38] Indirect nerve trauma Especially during a surgery Cone biopsy (rare complication) 55% of hysterectomy patients have microneuromas, associated with childbirth Traction injury Chronic repetitive stress - Indirect nerve trauma Especially during a surgery Cone biopsy (rare complication) 55% of hysterectomy patients have microneuromas, associated with childbirth Traction injury Chronic repetitive stress - Especially during a surgery - Cone biopsy (rare complication) - 55% of hysterectomy patients have microneuromas, associated with childbirth - Traction injury - Chronic repetitive stress - Morton's neuroma is associated with: Wearing tight shoes and high heels Overpronation Abnormal positioning of toes Flat feet Forefoot problems such as: Bunions Hammer toes High foot arches - Wearing tight shoes and high heels - Overpronation - Abnormal positioning of toes - Flat feet - Forefoot problems such as: Bunions Hammer toes - Bunions - Hammer toes - High foot arches # Epidemiology and Demographics - Neuroma is an uncommon disease[38] ## Age - Neuroma is more commonly observed among patients aged between 15 to 50 years old[38] - Neuroma is more commonly observed among middle aged adults ## Gender - Females are more commonly affected with neuroma than males - The female to male ratio is approximately 5:1[38] ## Race - There is no racial predilection for neuroma # Risk Factors - Common risk factors in the development of neuroma include:[37] Improper footwear/tight shoes High-impact sports (e.g., rock-climbing, ballet dancing, jogging, running, snow skiing) Overpronation - Improper footwear/tight shoes - High-impact sports (e.g., rock-climbing, ballet dancing, jogging, running, snow skiing) - Overpronation # Natural History, Complications and Prognosis - The majority of patients with neuroma are symptomatic at the time of diagnosis[1] - Early clinical features include neuropathic pain or local tenderness - If left untreated, the majority of patients with neuroma may progress to develop difficulty walking and limping - A significant complication of neuroma is chronic neuropathic pain - Prognosis is generally good, and the survival rate of patients with neuroma is 99%[39][40] # Diagnosis ## Symptoms - Neuroma is usually asymptomatic - Symptoms of neuroma may include:[1] Focal area of traumatic neuropathic pain radiating to toes, with the presence of a typical trigger point in the area of a neuroma (especially with the pressure application) causing the patient to feel:[41] Shooting Burning Stabbing Raw Gnawing Sickening sensations Numbness Paresthesia over the injured area Dysesthesia (painful hypersensitivity to normal light tactile stimuli) Functional impairment Psychological distress (severely decreasing the quality of life) - Focal area of traumatic neuropathic pain radiating to toes, with the presence of a typical trigger point in the area of a neuroma (especially with the pressure application) causing the patient to feel:[41] Shooting Burning Stabbing Raw Gnawing Sickening sensations - Shooting - Burning - Stabbing - Raw - Gnawing - Sickening sensations - Numbness - Paresthesia over the injured area - Dysesthesia (painful hypersensitivity to normal light tactile stimuli) - Functional impairment - Psychological distress (severely decreasing the quality of life) ## Physical Examination - Patients with neuroma usually appear with antalgic posture[1] - Physical examination may be remarkable for: Tenderness to palpation Limitation of range of motion Dysesthetic pain Mulder's sign: Replication of symptoms or clicking sensations upon direct pressure between the metatarsal heads or compression of transverse arch in forefoot between the finger and thumb - Tenderness to palpation - Limitation of range of motion - Dysesthetic pain - Mulder's sign: Replication of symptoms or clicking sensations upon direct pressure between the metatarsal heads or compression of transverse arch in forefoot between the finger and thumb - Replication of symptoms or clicking sensations upon direct pressure between the metatarsal heads or compression of transverse arch in forefoot between the finger and thumb ## Laboratory Findings - There are no specific laboratory findings associated with neuroma[37] ## Imaging Findings ### MRI - On MRI, characteristic findings of neuroma include:[42][43][44][45][46][47][48][49][7][50][51][7] Dumbbell/ovoid-shaped lesion at a similar position to that described on ultrasound T1: typically low-to-iso signal T2: typically low signal but can sometimes be intermediate in signal T1 C+ (Gd): tends to show intense enhancement - Dumbbell/ovoid-shaped lesion at a similar position to that described on ultrasound - T1: typically low-to-iso signal - T2: typically low signal but can sometimes be intermediate in signal - T1 C+ (Gd): tends to show intense enhancement - On MRI, characteristic findings of traumatic neuroma include:[1] Fusiform swelling of a nerve or a bulbous mass at a nerve end The parent nerve of some small nerve may difficult or impossible to discern T2/STIR: inhomogeneous hyperintensity (may have a hypointense rim) T1 C+ (Gd): variable contrast enhancement - Fusiform swelling of a nerve or a bulbous mass at a nerve end - The parent nerve of some small nerve may difficult or impossible to discern - T2/STIR: inhomogeneous hyperintensity (may have a hypointense rim) - T1 C+ (Gd): variable contrast enhancement ### Ultrasound - Ultrasound can help distinguish neuroma from:[52][53][54] Intermetatarsal bursal swelling or Synovitis in adjacent joints - Intermetatarsal bursal swelling or - Synovitis in adjacent joints - On ultrasound, neuroma is characterized by the following findings:[1][55][56][57][58][59][60][61][62][6][63] Round to ovoid Well-defined, hypoechoic lesion Located in the intermetatarsal space proximal to the metatarsal head - Round to ovoid - Well-defined, hypoechoic lesion - Located in the intermetatarsal space proximal to the metatarsal head - On ultrasound, traumatic neuroma is characterized by the following findings:[1] Swollen nerve (mass-like) Hypoechoic Loss of normal fibrillar pattern Usually small, but may be as large as 5 cm - Swollen nerve (mass-like) - Hypoechoic - Loss of normal fibrillar pattern - Usually small, but may be as large as 5 cm # Treatment ## Medical Therapy ### Conservative therapy for Morton's neuroma - Morton's neuroma should be managed conservatively before proceeding to expensive diagnostic procedures - Conservative measures for pain relief include:[64][65][66][67][68][69] Decreasing pressure on the metatarsal heads by using: Metatarsal support Metatarsal bars Padding techniques (it's important to place inserts properly just proximal to the metatarsal head), such as: Metatarsal pads Toe crest pads Tapping the toe area Shoe inserts (orthotics) help in correcting any mechanical imbalance in the foot Specialized orthopedic shoes Comfortable shoes (with the help of a professional shoe fitting device) having: Wider toe box allowing spread of metatarsal heads Low heels Good arch support Physical therapy Ice massage Strength exercises for intrinsic foot muscles Resting - Decreasing pressure on the metatarsal heads by using: Metatarsal support Metatarsal bars Padding techniques (it's important to place inserts properly just proximal to the metatarsal head), such as: Metatarsal pads Toe crest pads Tapping the toe area Shoe inserts (orthotics) help in correcting any mechanical imbalance in the foot Specialized orthopedic shoes Comfortable shoes (with the help of a professional shoe fitting device) having: Wider toe box allowing spread of metatarsal heads Low heels Good arch support - Metatarsal support - Metatarsal bars - Padding techniques (it's important to place inserts properly just proximal to the metatarsal head), such as: Metatarsal pads Toe crest pads - Metatarsal pads - Toe crest pads - Tapping the toe area - Shoe inserts (orthotics) help in correcting any mechanical imbalance in the foot - Specialized orthopedic shoes - Comfortable shoes (with the help of a professional shoe fitting device) having: Wider toe box allowing spread of metatarsal heads Low heels Good arch support - Wider toe box allowing spread of metatarsal heads - Low heels - Good arch support - Physical therapy - Ice massage - Strength exercises for intrinsic foot muscles - Resting ### Non-conservative medical therapy - When conservative measures fail, following medical therapy is used for non-surgical treatment of neuroma:[1] Tricyclic antidepressants Anticonvulsants (more effective) Serotonin-norepinephrine reuptake inhibitors Ultrasound-guided interdigital injection of following nerve blocking agents via dorsal approach into the site of tenderness:[70][71][72][73][74][75][76][77][78][79][80][81][82][83][9][84][85][86][87] Steroid Local anaesthetic Anti-inflammatory drugs (orally or injected into the toe area), such as: Ibuprofen (Advil, Motrin) Naproxen (Aleve, Naprosyn) Painkillers (not recommended for long-term treatment) - Tricyclic antidepressants - Anticonvulsants (more effective) - Serotonin-norepinephrine reuptake inhibitors - Ultrasound-guided interdigital injection of following nerve blocking agents via dorsal approach into the site of tenderness:[70][71][72][73][74][75][76][77][78][79][80][81][82][83][9][84][85][86][87] Steroid Local anaesthetic - Steroid - Local anaesthetic - Anti-inflammatory drugs (orally or injected into the toe area), such as: Ibuprofen (Advil, Motrin) Naproxen (Aleve, Naprosyn) - Ibuprofen (Advil, Motrin) - Naproxen (Aleve, Naprosyn) - Painkillers (not recommended for long-term treatment) ## Surgery - Surgical excision is the treatment of choice for neuroma[88][89][90][91][92][93][94][95][96][97][98][99][100][39] - Surgical excision is associated with a relatively favorable success rate of approximately 80% - Recurrence rate after surgery is as high as 50% ## Prevention - There are no primary preventive measures available for neuroma[1] - Secondary prevention measures include: personal hygiene measures, such as wearing ergonomic shoes # Differential Diagnosis - Neuroma must be differentiated from other diseases that cause forefoot pain and numbness such as:[1][38] Stress fracture (neck of the metatarsal) Rheumatoid arthritis Hammer toe Neurofibroma - Stress fracture (neck of the metatarsal) - Rheumatoid arthritis - Hammer toe - Neurofibroma	https://www.wikidoc.org/index.php/Facial_nerve_neuroma
e527b603ee30be7dcfe65741d6f166cd44c4c2fc	wikidoc	Failure	Failure Failure (fail, phail or flop) in general refers to the state or condition of not meeting a desirable or intended objective. It may be viewed as the opposite of success. Product failure ranges from failure to sell the product to fracture of the product, in the worst cases leading to personal injury, the province of forensic engineering. # Criteria for failure The criteria for failure are heavily dependent on context of use, and may be relative to a particular observer or belief system. A situation considered to be a failure by one might be considered a success by another, particularly in cases of direct competition or a zero-sum game. As well, the degree of success or failure in a situation may be differently viewed by distinct observers or participants, such that a situation that one considers to be a failure, another might consider to be a success, a qualified success or a neutral situation. It may also be difficult or impossible to ascertain whether a situation meets criteria for failure or success due to ambiguous or ill-defined definition of those criteria. Finding useful and effective criteria, or heuristics, to judge the success or failure of a situation may itself be a significant task. # Types of failure Failure can be differentially perceived from the viewpoints of the evaluators. A person who is only interested in the final outcome of an activity would consider it to be an Outcome Failure if the core issue has not been resolved or a core need is not met. A failure can also be a process failure whereby although the activity is completed successfully, a person may still feel dissatisfied if the underlying process is perceived to be below expected standard or benchmark. - Failure to anticipate - Failure to perceive # Commercial failures A commercial failure is a product that does not reach expectations of success, failing to come even close. A major flop goes one step further and is recognized for its complete lack of success. Most of the items listed below had high expectations, significant financial investments, and/or widespread publicity, but fell far short of success. Due to the subjective nature of "success" and "meeting expectations", there can be disagreement about what constitutes a "major flop." - For flops in computer and video gaming, see List of commercial failures in computer and video gaming - For company failures related to the 1997–2001 Dot-com bubble, see Dot-com company - See also Vaporware # Fail internet meme "Fail" is the name of a popular internet meme where users superimpose the word "fail" onto embarrassing or compromising photos. The G4 television channel has a web feature called "Epic Fail" that denotes major gaffs in popular culture - a mainstream play on the meme. Fail Dogs, an animal version, made the front page of Digg in February, 2008.	Failure Failure (fail, phail or flop) in general refers to the state or condition of not meeting a desirable or intended objective. It may be viewed as the opposite of success. Product failure ranges from failure to sell the product to fracture of the product, in the worst cases leading to personal injury, the province of forensic engineering. # Criteria for failure The criteria for failure are heavily dependent on context of use, and may be relative to a particular observer or belief system. A situation considered to be a failure by one might be considered a success by another, particularly in cases of direct competition or a zero-sum game. As well, the degree of success or failure in a situation may be differently viewed by distinct observers or participants, such that a situation that one considers to be a failure, another might consider to be a success, a qualified success or a neutral situation. It may also be difficult or impossible to ascertain whether a situation meets criteria for failure or success due to ambiguous or ill-defined definition of those criteria. Finding useful and effective criteria, or heuristics, to judge the success or failure of a situation may itself be a significant task. # Types of failure Failure can be differentially perceived from the viewpoints of the evaluators. A person who is only interested in the final outcome of an activity would consider it to be an Outcome Failure if the core issue has not been resolved or a core need is not met. A failure can also be a process failure whereby although the activity is completed successfully, a person may still feel dissatisfied if the underlying process is perceived to be below expected standard or benchmark. - Failure to anticipate - Failure to perceive # Commercial failures A commercial failure is a product that does not reach expectations of success, failing to come even close. A major flop goes one step further and is recognized for its complete lack of success. Most of the items listed below had high expectations, significant financial investments, and/or widespread publicity, but fell far short of success. Due to the subjective nature of "success" and "meeting expectations", there can be disagreement about what constitutes a "major flop." - For flops in computer and video gaming, see List of commercial failures in computer and video gaming - For company failures related to the 1997–2001 Dot-com bubble, see Dot-com company - See also Vaporware # Fail internet meme "Fail" is the name of a popular internet meme where users superimpose the word "fail" onto embarrassing or compromising photos.[1][2][3] The G4 television channel has a web feature called "Epic Fail" that denotes major gaffs in popular culture - a mainstream play on the meme.[4] Fail Dogs, an animal version, made the front page of Digg in February, 2008. [5]	https://www.wikidoc.org/index.php/Failure
df34908fac9ec5bec107e4203a21549b891a0a68	wikidoc	Falafel	Falafel Falafel (Template:Lang-ar Template:Audio, Template:Lang-he; also known in Egypt and Sudan as ta'meya, Arabic طعمية), is a fried ball or patty made from spiced fava beans and/or chickpeas. It has become a popular form of fast food in the Levant and in the Mashriq (Arab East), where it is also served as a mezze (snack or tapas). The word "falafel" is the plural of the Arabic word فلفل (filfil), meaning pepper. Variant spellings in English include felafel and filafil. Falafel is usually served as a sandwich wrapped in pita bread, and outside the Middle East, the term "falafel" commonly refers to this sandwich—falafel in a pita is typical street food or fast food. Along with the falafel balls, which may be crushed onto the bread or added whole, topping variations are usually included. Falafel balls may also be eaten alone as a snack or served as part of a mezze. During Ramadan they are sometimes eaten as part of an iftar, the meal which breaks the daily fast after sunset. Falafel has been part of the diet of Mizrahi Jews for centuries and is a staple of the Israeli diet. It has become the national dish of Israel. Falafel is now seen as a uniting, pan-Middle-Eastern dish. In recent years, immigration from the Middle East to Western countries has brought with it a broader availability of Middle Eastern cuisine, and the falafel sandwich has become a popular and iconic food within alternative fast food or slow food movements, and indeed has spread worldwide. They are also used as a vegan alternative filler to a Döner kebab in many countries. # Ingredients Falafel is made from fava beans or chickpeas or a combination of the two. The Egyptian variation uses exclusively fava beans, while other variations may only use chickpeas. Unlike many other bean patties, in falafel the beans are not cooked prior to use. Instead they are soaked, possibly skinned, then ground with the addition of a small quantity of onion, parsley, spices (including cumin), and bicarbonate of soda, and deep fried at a high temperature. Sesame seeds may be added to the balls before they are fried; this is particularly common when falafel is served as a dish on its own rather than as a sandwich filling. Recent culinary trends have seen the triumph of the chickpea falafel over the fava bean falafel. Chickpea falafels are served across the Middle East, and have been popularized by expatriates of those countries living abroad. ## Topping variations There is more than one way to make a falafel sandwich. Outside the Middle East a Greek-style pita bread is often used as a pocket and stuffed with the different ingredients; in Arab countries a round khubz bread, 'eish' in Egypt, is halved, and the two resulting round pieces are used to create a cigar-shaped wrap. In Arab countries, hummus (chickpeas pureed with tahini) is rarely an ingredient. The usual sauce is tahini (sesame seed paste) thinned with water and lemon. The most common salad ingredients are tomato and parsley. In Lebanon parsley is mixed with chopped mint leaves. It is also common in Syria and Lebanon to add pickles; the two canonical ones are pickled turnip, colored pink with beetroot, and pickled cucumber. Many Israelis like to add fried aubergine (eggplant) in addition to the regular "Israeli Salad" (chopped cucumbers and tomatoes). In Israel, Lebanon and the UAE, French fries are a frequent addition. Also in Israel the pita and hummus are common. Recently, there has been a new "filled" falafel, its center usually consisting of ground meat or minced onions. These fillings are wrapped by the uncooked falafel mixture, and then deep fried. The salads or the pita itself may be seasoned with sumac or salt; alternatively, these may be applied to the top. In Syria, sumac is practically a universal accompaniment to falafel, whether in a sandwich or otherwise. Falafel is becoming an increasingly common sandwich or snack food. # Related dishes - In Indian cuisine, ambode is a fried ball of soaked chickpeas. It is usually flattened and pan-fried, and served with chutney. Alternatively, in the South Indian cuisine, paruppu vadai is used to refer to flattened, fried balls (or fritters) of a mix of lentils and chickpeas. - In Italian cuisine, there is a chickpea fritter called frittata di ceci; other similar Italian dishes include panelle and farinata. - Acarajé, an Afro-Brazilian street food from the northeastern state of Bahia, are pureed black-eyed peas formed into a ball and then deep-fried in palm oil. # Trivia - Falafel is often referred to as the "national food of Israel". - A Falafel vendor is featured in the 2005 film Batman Begins. - In a 2005 BBC training video on the Middle East conflict, falafel is used by the BBC's Middle East Editor Jeremy Bowen as a metaphor both for the shared heritage of people in the region as well as for the complicated and conflicting truth claims often made by Israelis and Palestinians. - TV personality Bill O'Reilly is nicknamed the Falafel Guy, after mistaking the loofah sponge with falafel in an alleged phone conversation with Andrea Mackris. - In the TV series Hercules: The Legendary Journeys, a character portrayed by Paul Norell is known as Falafel, because he is a Falafel vendor.	Falafel Template:Otheruses4 Falafel (Template:Lang-ar Template:Audio, Template:Lang-he; also known in Egypt and Sudan as ta'meya, Arabic طعمية), is a fried ball or patty made from spiced fava beans and/or chickpeas. It has become a popular form of fast food in the Levant and in the Mashriq (Arab East), where it is also served as a mezze (snack or tapas). The word "falafel" is the plural of the Arabic word فلفل (filfil), meaning pepper.[1] Variant spellings in English include felafel and filafil. Falafel is usually served as a sandwich wrapped in pita bread, and outside the Middle East, the term "falafel" commonly refers to this sandwich—falafel in a pita is typical street food or fast food. Along with the falafel balls, which may be crushed onto the bread or added whole, topping variations are usually included. Falafel balls may also be eaten alone as a snack or served as part of a mezze. During Ramadan they are sometimes eaten as part of an iftar, the meal which breaks the daily fast after sunset. Falafel has been part of the diet of Mizrahi Jews for centuries and is a staple of the Israeli diet. It has become the national dish of Israel.[2] Falafel is now seen as a uniting, pan-Middle-Eastern dish. In recent years, immigration from the Middle East to Western countries has brought with it a broader availability of Middle Eastern cuisine, and the falafel sandwich has become a popular and iconic food within alternative fast food or slow food movements, and indeed has spread worldwide. They are also used as a vegan alternative filler to a Döner kebab in many countries. # Ingredients Falafel is made from fava beans or chickpeas or a combination of the two. The Egyptian variation uses exclusively fava beans, while other variations may only use chickpeas. Unlike many other bean patties, in falafel the beans are not cooked prior to use. Instead they are soaked, possibly skinned, then ground with the addition of a small quantity of onion, parsley, spices (including cumin), and bicarbonate of soda, and deep fried at a high temperature. Sesame seeds may be added to the balls before they are fried; this is particularly common when falafel is served as a dish on its own rather than as a sandwich filling. Recent culinary trends have seen the triumph of the chickpea falafel over the fava bean falafel. Chickpea falafels are served across the Middle East, and have been popularized by expatriates of those countries living abroad. ## Topping variations There is more than one way to make a falafel sandwich. Outside the Middle East a Greek-style pita bread is often used as a pocket and stuffed with the different ingredients; in Arab countries a round khubz bread, 'eish' in Egypt, is halved, and the two resulting round pieces are used to create a cigar-shaped wrap. In Arab countries, hummus (chickpeas pureed with tahini) is rarely an ingredient. The usual sauce is tahini (sesame seed paste) thinned with water and lemon. The most common salad ingredients are tomato and parsley. In Lebanon parsley is mixed with chopped mint leaves. It is also common in Syria and Lebanon to add pickles; the two canonical ones are pickled turnip, colored pink with beetroot, and pickled cucumber. Many Israelis like to add fried aubergine (eggplant) in addition to the regular "Israeli Salad" (chopped cucumbers and tomatoes). In Israel, Lebanon and the UAE, French fries are a frequent addition. Also in Israel the pita and hummus are common. Recently, there has been a new "filled" falafel, its center usually consisting of ground meat or minced onions. These fillings are wrapped by the uncooked falafel mixture, and then deep fried. The salads or the pita itself may be seasoned with sumac or salt; alternatively, these may be applied to the top. In Syria, sumac is practically a universal accompaniment to falafel, whether in a sandwich or otherwise. Falafel is becoming an increasingly common sandwich or snack food. # Related dishes - In Indian cuisine, ambode is a fried ball of soaked chickpeas. It is usually flattened and pan-fried, and served with chutney. Alternatively, in the South Indian cuisine, paruppu vadai is used to refer to flattened, fried balls (or fritters) of a mix of lentils and chickpeas. - In Italian cuisine, there is a chickpea fritter called frittata di ceci; other similar Italian dishes include panelle and farinata. - Acarajé, an Afro-Brazilian street food from the northeastern state of Bahia, are pureed black-eyed peas formed into a ball and then deep-fried in palm oil. # Trivia - Falafel is often referred to as the "national food of Israel". - A Falafel vendor is featured in the 2005 film Batman Begins. - In a 2005 BBC training video on the Middle East conflict, falafel is used by the BBC's Middle East Editor Jeremy Bowen as a metaphor both for the shared heritage of people in the region as well as for the complicated and conflicting truth claims often made by Israelis and Palestinians. - TV personality Bill O'Reilly is nicknamed the Falafel Guy, after mistaking the loofah sponge with falafel in an alleged phone conversation with Andrea Mackris. - In the TV series Hercules: The Legendary Journeys, a character portrayed by Paul Norell is known as Falafel, because he is a Falafel vendor.	https://www.wikidoc.org/index.php/Falafel
f353647a857241183d24c42e3dad728ed751dd70	wikidoc	Falling	Falling Falling is movement due to gravity, but also has other uses not directly related to gravity. # Sensation A sensation of falling occurs when the labyrinth or vestibular apparatus, a system of fluid-filled passages in the inner ear, detects motion. The same system also detects rotary motion. A similar sensation of falling can be induced when the eyes detect rapid apparent motion with respect to the environment. This system enables us to keep our balance by signalling when a physical correction is necessary. When a human is in free fall in an orbiting spacecraft, or in an aircraft in a steep dive, the sensation of falling is constant, and the sensation of there being an "up" and a "down" is missing or much attenuated. Some medical conditions, known as balance disorders, also induce the sensation of falling. # Accidents Falling is a major cause of personal injury, especially for the elderly whose vision, nerve conduction and muscles are weaker, whose vestibular sense is diminished, whose neurological responses are extended, and whose bones have grown brittle. Builders and miners represent worker categories representing high rates of fall injuries. The WHO estimate (2002) that 392,000 people die in falls every year. In 1972, Vesna Vulović survived a fall from 33,000ft without a parachute. ## Falls in the workplace Falls from elevation hazards are present at most every jobsite, and many workers are exposed to these hazards daily. As such, falls are an important topic for occupational safety and health services. Any walking/working surface could be a potential fall hazard. An unprotected side or edge which is 6 feet or more above a lower level should be protected from falling by the use of a guardrail system, safety net system, or personal fall arrest system. These hazardous exposures exist in many forms, and can be as seemingly innocuous as changing a light bulb from a step ladder to something as high-risk as connecting bolts on high steel at 200 feet in the air. Falls are the second leading cause of work-related death in the U.S. In 2000, 717 workers died of injuries caused by falls from ladders, scaffolds, buildings, or other elevations. ## Falls from buildings Falls from buildings are often accidental but can also be caused intentionally, such as by defenestration. Injuries resulting in falls from buildings vary depending on the building's height, and also depend on the type of person (infant, child, adult, elderly adult, etc.) Falls from the second floor usually result in injuries, but are not fatal. Surviving a fall from higher points requires not injuring your head or pelvis. ## Elderly Stephen Lord at the University of New South Wales studied 80,000 elderly persons in Australia and found that the risk of falling increases for any who are taking multiple prescription medications and for all who are taking psychoactive drugs. This increased risk was demonstrated through the use of a variety of balance and reaction time tests. Inexplicably, the older men when matched with women of identical height, weight, and age, on average, performed measurably better in all of the balance and reaction time tests. # Drug Side Effect - Flurazepam - Perampanel	Falling Falling is movement due to gravity, but also has other uses not directly related to gravity. # Sensation A sensation of falling occurs when the labyrinth or vestibular apparatus, a system of fluid-filled passages in the inner ear, detects motion. The same system also detects rotary motion. A similar sensation of falling can be induced when the eyes detect rapid apparent motion with respect to the environment. This system enables us to keep our balance by signalling when a physical correction is necessary. When a human is in free fall in an orbiting spacecraft, or in an aircraft in a steep dive, the sensation of falling is constant, and the sensation of there being an "up" and a "down" is missing or much attenuated. Some medical conditions, known as balance disorders, also induce the sensation of falling. # Accidents Falling is a major cause of personal injury, especially for the elderly whose vision, nerve conduction and muscles are weaker, whose vestibular sense is diminished, whose neurological responses are extended, and whose bones have grown brittle. Builders and miners represent worker categories representing high rates of fall injuries. The WHO estimate (2002) that 392,000 people die in falls every year. In 1972, Vesna Vulović survived a fall from 33,000ft without a parachute. ## Falls in the workplace Falls from elevation hazards are present at most every jobsite, and many workers are exposed to these hazards daily. As such, falls are an important topic for occupational safety and health services. Any walking/working surface could be a potential fall hazard. An unprotected side or edge which is 6 feet or more above a lower level should be protected from falling by the use of a guardrail system, safety net system, or personal fall arrest system. [1] These hazardous exposures exist in many forms, and can be as seemingly innocuous as changing a light bulb from a step ladder to something as high-risk as connecting bolts on high steel at 200 feet in the air. Falls are the second leading cause of work-related death in the U.S. [2] In 2000, 717 workers died of injuries caused by falls from ladders, scaffolds, buildings, or other elevations.[2] ## Falls from buildings Falls from buildings are often accidental but can also be caused intentionally, such as by defenestration. Injuries resulting in falls from buildings vary depending on the building's height, and also depend on the type of person (infant, child, adult, elderly adult, etc.) Falls from the second floor usually result in injuries, but are not fatal. Surviving a fall from higher points requires not injuring your head or pelvis.[3] ## Elderly Stephen Lord at the University of New South Wales studied 80,000 elderly persons in Australia and found that the risk of falling increases for any who are taking multiple prescription medications and for all who are taking psychoactive drugs. This increased risk was demonstrated through the use of a variety of balance and reaction time tests. Inexplicably, the older men when matched with women of identical height, weight, and age, on average, performed measurably better in all of the balance and reaction time tests.[citation needed] # Drug Side Effect - Flurazepam - Perampanel	https://www.wikidoc.org/index.php/Falling
30a3d25d5689349a4062e39f9678757a11a689d3	wikidoc	Fam158a	Fam158a UPF0172 protein FAM158A, also known as c14orf122 or CGI112, is a protein that in humans is encoded by the FAM158A gene located on chromosome 14q11.2. Human FAM158A and its paralogs in other species are part of the uncharacterized protein family UPF0172 family, which is a subset of the JAB1/Mov34/MPN/PAD-1 ubiquitin protease protein family. The MPN superfamily contributes to ubiquitination and de-ubiquitination activity within the cell. The UPF0172 subset no longer has a functional ubiquitination domain and the function is uncharacterized. # Gene Fam158a is positioned between PSME1 (antisense) and PSME2 (sense). RNF31 is upstream and antisense to Fam158a. DCAF11 and FITM1 are both upstream of PSME1 antisense to Fam158a. PSME1 is a subunit of the 11S regulator which is a part of the immunoproteasome responsible for cleaving MHC class I peptides. PSME2 is another subunit of the 11S regulator RNF31 encodes a protein which contains a ring finger motif found in several proteins which mediate protein-DNA and protein-protein interactions. FITM1 is a protein involved in fat storage. DCAF11 is a protein that is known to interact with COP9 and has several alternative transcripts. - Conceptual Translation of Fam158a annotated with predicted phosphorylation sites, exon boundaries, and conserved regions Conceptual Translation of Fam158a annotated with predicted phosphorylation sites, exon boundaries, and conserved regions - Fam158a chromosomal location and neighboring genes Fam158a chromosomal location and neighboring genes - transcription factor binding sites in the promoter of Fam158a transcription factor binding sites in the promoter of Fam158a ## Promoter The promoter is conserved as far back as Danio rerio. Softberry's FGenesH predicts two upstream promoters, a TATA Box 461bp upstream of the start site and another uncharacterized promoter 83bp upstream. Genomatix ElDorado predicts several transcription factor binding sites in the promoter region. found that Fam158a expression increases in GATA3 mutants, and as seen in the table, the Fam158a promoter region contains a Gata binding site. Another study shows FAM158A responds to Beta-catenin depletion. Although there are no known beta-catenin binding sites in the promoter, there is a NeuroD site and NeuroD responds to beta-catenin. # Homology ## Paralogs The paralog to FAM158A is commonly known as Cox4NB and is located at 16q24. It is also referred to as Cox4AL, Noc4, and Fam158b. The paralog partially overlaps COX4I1 and has two isoforms. Isoform 1 is the complete isoform at 210 amino acids while isoform 2 is 126 amino acids. Like Fam158a, Cox4NB is highly conserved in Eukaryotes from mammals to as far back as fish. Currently there is no known function of Cox4NB. In most fish and further back there is a single homolog, the predecessor to Cox4NB and Fam158a. ## Homologs As shown in the alignment, the protein is highly conserved chemically, although the exact sequence varies. There are also several regions of high conservation (highlighted by the red boxes). The degree of conservation follows the expected evolutionary pattern. The graph demonstrates this by plotting each species protein similarity to the human protein vs. the time since the species shared a common ancestor. The unrooted phylogenetic tree also demonstrates this relationship. # Protein Fam158a has an isoelectric point of 5.5 and a molecular weight of 23 kiloDaltons. Fam158a does not have any predicted signal peptides or transmembrane regions. There are several predicted phosphorylation sites. marked in the conceptual translation as well as the predicted secondary structure. There are no regions significantly different from other human proteins with regard to composition, regions of polarity, or regions of hydrophobicity. iPsortII predicts no signal peptides and localizes Fam158a to the cytoplasm- I-Tasser predicts several structures for Fam158a and the best prediction is shown. Swiss Model predicts two potential protein structures, as seen in the images. The first structure predicts the protein forms a protein dimer, the second as a monomer. Rual et al. found that Fam158a interacts with a protein called TTC35. The function of TTC35 is unknown but it is also known to interact with Cox4NB and Ubiquitin C. - Predicted Protein Structures using SwissModel Predicted Protein Structures using SwissModel - Predicted Fam158a structure from I Tasser Predicted Fam158a structure from I Tasser # Function Fam158a is nearly ubiquitously expressed throughout the human body. The homolog in mice also shows expression throughout the entire body. Several micro-arrays demonstrate the variable expression of Fam158a in response to other factors and in various cancer types. None of this information gives any indication of a specific function but the wide expression of the gene and its high conservation indicate that Fam158a plays an important role in cellular function. # Clinical significance There are several diseases associated with deletions of 14q11.2, but none have been linked specifically to Fam158a. T-Lymphocytic Leukemia with or without ataxia telangiectasia has been associated with inversions and tandem translocations of 14q11 and 14q32 and other chromosomes. Also, syndactyly type 2 has been isolated to 14q11.2-12. This form of syndactyly is characterized by fusion of the third and fourth digits of the hand and the fourth and fifth digits of the foot in addition to other fusions and malformations.	Fam158a UPF0172 protein FAM158A, also known as c14orf122 or CGI112, is a protein that in humans is encoded by the FAM158A gene located on chromosome 14q11.2.[1][2] Human FAM158A and its paralogs in other species are part of the uncharacterized protein family UPF0172 family, which is a subset of the JAB1/Mov34/MPN/PAD-1 ubiquitin protease protein family. The MPN superfamily contributes to ubiquitination and de-ubiquitination activity within the cell. The UPF0172 subset no longer has a functional ubiquitination domain and the function is uncharacterized.[3] # Gene Fam158a is positioned between PSME1 (antisense) and PSME2 (sense).[4] RNF31 is upstream and antisense to Fam158a. DCAF11 and FITM1 are both upstream of PSME1 antisense to Fam158a. PSME1 is a subunit of the 11S regulator which is a part of the immunoproteasome responsible for cleaving MHC class I peptides.[5] PSME2 is another subunit of the 11S regulator[6] RNF31 encodes a protein which contains a ring finger motif found in several proteins which mediate protein-DNA and protein-protein interactions.[7] FITM1 is a protein involved in fat storage.[8] DCAF11 is a protein that is known to interact with COP9 and has several alternative transcripts.[9] - Conceptual Translation of Fam158a annotated with predicted phosphorylation sites, exon boundaries, and conserved regions Conceptual Translation of Fam158a annotated with predicted phosphorylation sites, exon boundaries, and conserved regions - Fam158a chromosomal location and neighboring genes Fam158a chromosomal location and neighboring genes - transcription factor binding sites in the promoter of Fam158a transcription factor binding sites in the promoter of Fam158a ## Promoter The promoter is conserved as far back as Danio rerio. Softberry's FGenesH predicts two upstream promoters, a TATA Box 461bp upstream of the start site and another uncharacterized promoter 83bp upstream.[citation needed] Genomatix ElDorado predicts several transcription factor binding sites in the promoter region.[citation needed][10] found that Fam158a expression increases in GATA3 mutants, and as seen in the table, the Fam158a promoter region contains a Gata binding site. Another study shows FAM158A responds to Beta-catenin depletion.[11] Although there are no known beta-catenin binding sites in the promoter, there is a NeuroD site and NeuroD responds to beta-catenin. # Homology ## Paralogs The paralog to FAM158A is commonly known as Cox4NB and is located at 16q24.[12] It is also referred to as Cox4AL, Noc4, and Fam158b. The paralog partially overlaps COX4I1 and has two isoforms. Isoform 1 is the complete isoform at 210 amino acids while isoform 2 is 126 amino acids.[13] Like Fam158a, Cox4NB is highly conserved in Eukaryotes from mammals to as far back as fish. Currently there is no known function of Cox4NB. In most fish and further back there is a single homolog, the predecessor to Cox4NB and Fam158a. ## Homologs As shown in the alignment, the protein is highly conserved chemically, although the exact sequence varies. There are also several regions of high conservation (highlighted by the red boxes). The degree of conservation follows the expected evolutionary pattern. The graph demonstrates this by plotting each species protein similarity to the human protein vs. the time since the species shared a common ancestor. The unrooted phylogenetic tree also demonstrates this relationship. # Protein Fam158a has an isoelectric point of 5.5[15] and a molecular weight of 23 kiloDaltons.[16] Fam158a does not have any predicted signal peptides or transmembrane regions. There are several predicted phosphorylation sites.[17][18] marked in the conceptual translation as well as the predicted secondary structure.[19] There are no regions significantly different from other human proteins with regard to composition, regions of polarity, or regions of hydrophobicity. iPsortII predicts no signal peptides and localizes Fam158a to the cytoplasm-[20] I-Tasser[21] predicts several structures for Fam158a and the best prediction is shown. Swiss Model[22] predicts two potential protein structures, as seen in the images. The first structure predicts the protein forms a protein dimer, the second as a monomer. Rual et al.[23] found that Fam158a interacts with a protein called TTC35. The function of TTC35 is unknown but it is also known to interact with Cox4NB and Ubiquitin C. - Predicted Protein Structures using SwissModel Predicted Protein Structures using SwissModel - Predicted Fam158a structure from I Tasser Predicted Fam158a structure from I Tasser # Function Fam158a is nearly ubiquitously expressed throughout the human body.[24] The homolog in mice also shows expression throughout the entire body.[25] Several micro-arrays demonstrate the variable expression of Fam158a in response to other factors and in various cancer types. None of this information gives any indication of a specific function but the wide expression of the gene and its high conservation indicate that Fam158a plays an important role in cellular function. # Clinical significance There are several diseases associated with deletions of 14q11.2, but none have been linked specifically to Fam158a. T-Lymphocytic Leukemia with or without ataxia telangiectasia has been associated with inversions and tandem translocations of 14q11 and 14q32 and other chromosomes.[26] Also, syndactyly type 2 has been isolated to 14q11.2-12.[27] This form of syndactyly is characterized by fusion of the third and fourth digits of the hand and the fourth and fifth digits of the foot in addition to other fusions and malformations.	https://www.wikidoc.org/index.php/Fam158a
257c87292764835f8d9c84dba0111232384246a4	wikidoc	Fam188a	Fam188a # Gene Fam188a is a protein found in humans. It is also known as Derp5 (Dermal Papilla Derived Protein 5,) c10orf97, or brain my042 protein. It is encoded by the Derp5 gene located on chromosome 10p13. Fam188a and its paralogs in other species are all members of the DUF4205 superfamily of protein domains. Fam188a is a highly conserved gene found in all vertebrates. Fam188a is a gene expressed throughout the body. - Predicted protein structure of Fam188a using I-TASSER Predicted protein structure of Fam188a using I-TASSER # Homology All mammalian species compared share a 95-99% homology similarity to Homo sapiens Fam188a. The reasons behind this are unknown, but it can be inferred that Fam188a must play an important role in proper cellular function in mammals, as even small changes over time in important genes can drastically alter their function. - Evolutionary comparison of different species' Fam188a Evolutionary comparison of different species' Fam188a Avians, Fish, and Insects also shared a similarity in the 30-40% range with Homo sapiens' Fam188a. Even though there are several hundred million years of divergence from Humans and insects, the fact that there is still a 40% similarity in insects seems to suggest that this gene hasn't changed extremely over such long timespans, and must have been important for other species as well long ago. The splice patterns in these other species aren't known, but in humans there are at least 19 different isoforms but with only 1 major paralog: Fam188b. This paralog differs structurally in 3 exons with Fam188a. - An evolutionary tree between various species that have homologs of Fam188a. An evolutionary tree between various species that have homologs of Fam188a. - Intron/exon map of Fam188a in Homo sapiens Intron/exon map of Fam188a in Homo sapiens # Protein Fam188a is a 445-Amino Acid chain. Structurally, it doesn't show many interesting regions that could easily set it apart from other proteins. Fam188a has no transmembrane domains, it has no sequence repeats. - Fam188a post-translational predicted protein secondary structure Fam188a post-translational predicted protein secondary structure - Fam188a predicted transcription factor binding sites Fam188a predicted transcription factor binding sites # Function and interacting proteins The I-TASSER protein folding results show that Fam188a's protein product has a similar structure to 1CFF, a Calmodulin binding peptide. Calmodulin is involved in cell apoptosis as well, so this can shed light on the theorized function of Fam188a as well. The protein fold is most functionally similar to 3LEW, a “SusD-like carbohydrate binding protein from Bacteroides vulgatus” (Joint Center for Structural Genomics). 3LEW shares a 90% similarity with Fam188a, and although not enough to make a concrete connection, it is enough to establish a base idea of related structures. Another protein that is functionally similar (81%) is 3SNX, a “putative SusD-like carbohydrate binding protein from Bacteroides thetaiotaomicron VPI-5482”. The function of Fam188a can be assumed to play a role in cell apoptosis, and that is because it shares structural similarities with other proteins that are involved in this process. Although there is no CARD-domain as would normally be found in an apoptotic peptide, fam188a does share a similar function with 1cffA, a “calmodulin binding peptide of the Ca2+ pump”. Since Calmodulin is known to cause apoptosis throughout various body tissues via the Ca2+ pump and 1cffA shares a 26% similarity with Fam188a, I can hypothesize that apoptosis truly is the function of Fam188a. Other molecules similar to Fam188a are 1linA, and 1qx7M, which share 23% and 18% structure similarity respectively, and both of these molecules deal with either the Ca2+ pump or Calmodulin expression as well. - Fam188a tissue expression throughout various body tissues Fam188a tissue expression throughout various body tissues - Expression locations of Fam188a in the human brain Expression locations of Fam188a in the human brain - File:Tissue expression of Fam188a microassay humans.tiff	Fam188a # Gene Fam188a is a protein found in humans. It is also known as Derp5 (Dermal Papilla Derived Protein 5,) c10orf97, or brain my042 protein. It is encoded by the Derp5 gene located on chromosome 10p13.[1][2] Fam188a and its paralogs in other species are all members of the DUF4205 superfamily of protein domains. Fam188a is a highly conserved gene found in all vertebrates. Fam188a is a gene expressed throughout the body.[3] - Predicted protein structure of Fam188a using I-TASSER Predicted protein structure of Fam188a using I-TASSER # Homology All mammalian species compared share a 95-99% homology similarity to Homo sapiens Fam188a. The reasons behind this are unknown, but it can be inferred that Fam188a must play an important role in proper cellular function in mammals, as even small changes over time in important genes can drastically alter their function. - Evolutionary comparison of different species' Fam188a Evolutionary comparison of different species' Fam188a Avians, Fish, and Insects also shared a similarity in the 30-40% range with Homo sapiens' Fam188a. Even though there are several hundred million years of divergence from Humans and insects, the fact that there is still a 40% similarity in insects seems to suggest that this gene hasn't changed extremely over such long timespans, and must have been important for other species as well long ago. The splice patterns in these other species aren't known, but in humans there are at least 19 different isoforms but with only 1 major paralog: Fam188b.[4] This paralog differs structurally in 3 exons with Fam188a. - An evolutionary tree between various species that have homologs of Fam188a. An evolutionary tree between various species that have homologs of Fam188a. - Intron/exon map of Fam188a in Homo sapiens Intron/exon map of Fam188a in Homo sapiens # Protein Fam188a is a 445-Amino Acid chain. Structurally, it doesn't show many interesting regions that could easily set it apart from other proteins. Fam188a has no transmembrane domains, it has no sequence repeats. - Fam188a post-translational predicted protein secondary structure Fam188a post-translational predicted protein secondary structure - Fam188a predicted transcription factor binding sites Fam188a predicted transcription factor binding sites # Function and interacting proteins The I-TASSER[5] protein folding results show that Fam188a's protein product has a similar structure to 1CFF,[6] a Calmodulin binding peptide. Calmodulin is involved in cell apoptosis as well, so this can shed light on the theorized function of Fam188a as well. The protein fold is most functionally similar to 3LEW,[7] a “SusD-like carbohydrate binding protein from Bacteroides vulgatus” (Joint Center for Structural Genomics). 3LEW shares a 90% similarity with Fam188a, and although not enough to make a concrete connection, it is enough to establish a base idea of related structures. Another protein that is functionally similar (81%) is 3SNX, a “putative SusD-like carbohydrate binding protein from Bacteroides thetaiotaomicron VPI-5482”.[8] The function of Fam188a can be assumed to play a role in cell apoptosis, and that is because it shares structural similarities with other proteins that are involved in this process. Although there is no CARD-domain as would normally be found in an apoptotic peptide, fam188a does share a similar function with 1cffA, a “calmodulin binding peptide of the Ca2+ pump”.[6] Since Calmodulin is known to cause apoptosis throughout various body tissues via the Ca2+ pump[9][10] and 1cffA shares a 26% similarity with Fam188a, I can hypothesize that apoptosis truly is the function of Fam188a. Other molecules similar to Fam188a are 1linA,[11] and 1qx7M, which share 23% and 18% structure similarity respectively, and both of these molecules deal with either the Ca2+ pump or Calmodulin expression as well. - Fam188a tissue expression throughout various body tissues Fam188a tissue expression throughout various body tissues - Expression locations of Fam188a in the human brain Expression locations of Fam188a in the human brain - File:Tissue expression of Fam188a microassay humans.tiff	https://www.wikidoc.org/index.php/Fam188a
ca61d7d151474829453ad99e503e0557af012bda	wikidoc	Fam221b	Fam221b FAM221B is a protein that in humans is encoded by the FAM221B gene . FAM221B is also known by the alias C9orf128, is expressed at low level, and is defined by 17 GenBank accessions . It is predicted to function in transcription regulation as a transcription factor. # Gene ## Locus FAM221B can be found around the end of the short arm of human chromosome 9. ## Expression patterns FAM221B is expressed at low levels in human and mouse tissues. Expression is highest in germ cell tissues and cells. This differential expression is most pronounced in testes tissue. Compared to Homo sapiens, Mus musculus shows more differential expression of FAM221B in testes tissue . Mature beta cells express FAM221B at higher rates than do fetal beta cells - FAM221B expression for BioGPS dataset in various tissues in Homo sapiens FAM221B expression for BioGPS dataset in various tissues in Homo sapiens - FAM221B expression for GEO dataset GDS 3113 in various tissues in Homo sapiens FAM221B expression for GEO dataset GDS 3113 in various tissues in Homo sapiens - FAM221B expression for BioGPS dataset in various tissues in Mus musculus FAM221B expression for BioGPS dataset in various tissues in Mus musculus - FAM221B expression for GEO dataset GDS 3142 in various tissues in Mus musculus FAM221B expression for GEO dataset GDS 3142 in various tissues in Mus musculus # mRNA ## Alternative splicing and isoforms FAM221B has a total of 5 transcript variants: the putative sequence, Isoform X1 , Isoform X2 , Isoform X3 , and Isoform X4. Isoform X4 does not exist in humans but is found in various primates. ## Exons There are a total of six exons in the putative sequence of FAM221B. However, a total of seven exons exist for FAM221B, as the seventh exon is an alternative exon. # Protein ## General characteristics The putative sequence for FAM221B is 402 amino acids long and weighs 45.4 kilodaltons. Amino acids expressed at abnormal rates include Histidine, Cysteine, Glutamic acid, and Tyrosine. When compared to typical proteins, FAM221B expresses Histidine at a much higher frequency at 6.0% of protein, Cysteine at a slightly higher frequency at 4.7% of protein, Glutamic acid at a slightly higher frequency at 11.4% of protein, and Tyrosine at a slightly lower frequency at 1.0% of protein . The isoelectric point of FAM221B is 5.264, suggesting FAM221B is an acidic protein at a normal physiological pH (7.4) . There is strong evidence that FAM221B is a protein found within the nucleus ## Compositional features FAM221B is predicted to have two distinct alpha helices in its secondary structure . Secondary structure predicting programs predict beta sheets but are not as consistent as the two alpha helices. ## Post-translational modifications FAM221B is predicted to have a high number of phosphorylation sites. ## Protein interactions There is evidence that FAM221B interacts with the proteins Autophagy related 13 (KIAA0652), RB1-inducible coiled-coil 1 (RB1CC1), and Ephrin-B3 (EFNB3) . These proteins are predicted to be localized in the nucleus at the same confidence level as FAM221B. # Homology and evolution FAM221B is conserved in Eutheria. However, both orthologous and paralogous transcripts predating ancestral Boroeutheria can be found. ## Paralogs One paralog exists for FAM221B in humans: FAM221A . FAM221A and FAM221B’s ancestral gene is predicted to have diverged in prokarya. ## Orthologs ## Homologous domains There are three conserved domains within FAM221B: DUF4475 super family , PRCC super family , and Caprin-1_C . DUF4475 is the most conserved domain of the three. # Clinical significance FAM221B is linked to mutations in the RNA component of RNase MRP, which causes pleiotropic human disease cartilage–hair hypoplasia. Also, as patients with acute lymphoblastic leukemia often carry genetic alterations in the short arm of human chromosome 9, FAM221B has two consistent non-synonymous amino acid variations associated with the disease. In acute lymphoblastic leukemia patients, Histidine is substituted for an Arginine at position 345, and a Leucine is substituted for a Phenylalanine at position 277 of the protein.	Fam221b FAM221B is a protein that in humans is encoded by the FAM221B gene [1] . FAM221B is also known by the alias C9orf128, is expressed at low level, and is defined by 17 GenBank accessions [2] . It is predicted to function in transcription regulation as a transcription factor. # Gene ## Locus FAM221B can be found around the end of the short arm of human chromosome 9. ## Expression patterns FAM221B is expressed at low levels in human and mouse tissues. Expression is highest in germ cell tissues and cells. This differential expression is most pronounced in testes tissue. Compared to Homo sapiens, Mus musculus shows more differential expression of FAM221B in testes tissue [3] [4] [5] [6] . Mature beta cells express FAM221B at higher rates than do fetal beta cells [7] . - FAM221B expression for BioGPS dataset in various tissues in Homo sapiens FAM221B expression for BioGPS dataset in various tissues in Homo sapiens - FAM221B expression for GEO dataset GDS 3113 in various tissues in Homo sapiens FAM221B expression for GEO dataset GDS 3113 in various tissues in Homo sapiens - FAM221B expression for BioGPS dataset in various tissues in Mus musculus FAM221B expression for BioGPS dataset in various tissues in Mus musculus - FAM221B expression for GEO dataset GDS 3142 in various tissues in Mus musculus FAM221B expression for GEO dataset GDS 3142 in various tissues in Mus musculus # mRNA ## Alternative splicing and isoforms FAM221B has a total of 5 transcript variants: the putative sequence, Isoform X1 [8] , Isoform X2 [9] , Isoform X3 [10] , and Isoform X4. Isoform X4 does not exist in humans but is found in various primates. ## Exons There are a total of six exons in the putative sequence of FAM221B. However, a total of seven exons exist for FAM221B, as the seventh exon is an alternative exon. # Protein ## General characteristics The putative sequence for FAM221B is 402 amino acids long and weighs 45.4 kilodaltons. Amino acids expressed at abnormal rates include Histidine, Cysteine, Glutamic acid, and Tyrosine. When compared to typical proteins, FAM221B expresses Histidine at a much higher frequency at 6.0% of protein, Cysteine at a slightly higher frequency at 4.7% of protein, Glutamic acid at a slightly higher frequency at 11.4% of protein, and Tyrosine at a slightly lower frequency at 1.0% of protein [14] . The isoelectric point of FAM221B is 5.264, suggesting FAM221B is an acidic protein at a normal physiological pH (7.4) [14] . There is strong evidence that FAM221B is a protein found within the nucleus [15] . ## Compositional features FAM221B is predicted to have two distinct alpha helices in its secondary structure [16] [17] [18] . Secondary structure predicting programs predict beta sheets but are not as consistent as the two alpha helices. ## Post-translational modifications FAM221B is predicted to have a high number of phosphorylation sites. ## Protein interactions There is evidence that FAM221B interacts with the proteins Autophagy related 13 (KIAA0652), RB1-inducible coiled-coil 1 (RB1CC1), and Ephrin-B3 (EFNB3) [19] . These proteins are predicted to be localized in the nucleus at the same confidence level as FAM221B. # Homology and evolution FAM221B is conserved in Eutheria. However, both orthologous and paralogous transcripts predating ancestral Boroeutheria can be found. ## Paralogs One paralog exists for FAM221B in humans: FAM221A [20] . FAM221A and FAM221B’s ancestral gene is predicted to have diverged in prokarya. ## Orthologs ## Homologous domains There are three conserved domains within FAM221B: DUF4475 super family [21] , PRCC super family [22] , and Caprin-1_C [23] . DUF4475 is the most conserved domain of the three. # Clinical significance FAM221B is linked to mutations in the RNA component of RNase MRP, which causes pleiotropic human disease cartilage–hair hypoplasia. Also, as patients with acute lymphoblastic leukemia often carry genetic alterations in the short arm of human chromosome 9, FAM221B has two consistent non-synonymous amino acid variations associated with the disease. In acute lymphoblastic leukemia patients, Histidine is substituted for an Arginine at position 345, and a Leucine is substituted for a Phenylalanine at position 277 of the protein.	https://www.wikidoc.org/index.php/Fam221b
e923fe1e0c43fa181a521c976130e706ce387d66	wikidoc	Fasudil	Fasudil # Overview Fasudil hydrochloride (INN) is a potent Rho-kinase inhibitor and vasodilator. Since it was discovered, it has been used for the treatment of cerebral vasospasm, which is often due to subarachnoid hemorrhage, as well as to improve the cognitive decline seen in stroke victims. It has been found to be effective for the treatment of pulmonary hypertension. It was demonstrated in February 2009 that fasudil could also be used to enhance memory and improve the prognosis of Alzheimers patients. # Pulmonary Hypertension Pulmonary hypertension (PH) is a cardiovascular disease characterized by a resting mean pulmonary arterial pressure exceeding 25 mmHg, or more than 30 mmHg during exercise. It arises from the pulmonary vascular remodeling accompanied by endothelial dysfunction, fibroblast activation, and endothelial cellular proliferation. Symptoms of PH include shortness of breath, chronic fatigue, dizziness, peripheral edema, cyanosis, and chest pain. If untreated, PH could lead to heart failure and death. PH is divided into 5 classifications: arterial, venous, hypoxemia, thromboembolic, and miscellaneous. # Molecular Mechanism Fasudil (HA-1077) is a selective RhoA/Rho kinase(ROCK) inhibitor. ROCK is an enzyme that plays an important role in mediating vasoconstriction and vascular remodeling in the pathogenesis of PH. ROCK induces vasoconstriction by phosphorylating the myosin-binding subunit of myosin light chain (MLC) phosphatase, thus decreasing MLC phosphatase activity and enhancing vascular smooth muscle contraction. ## Angiotensin-converting Enzyme (ACE) expression and Angiotensin-II (Ang-II) levels ACE is an enzyme that catalyzes the conversion of Angiotensin-I (Ang-I) to Angiotensin-II (Ang-II). Ang-II is a peptide hormone which increases blood pressure by initiating vasoconstriction and aldosterone secretion. ROCK increases ACE expression and activity in PH. By inhibiting ROCK with fasudil, circulating ACE and Ang-II are reduced, leading to a decrease in pulmonary vascular pressure. ## Endothelial Nitric Oxide Synthase (eNOS) expression eNOS mediates the production of the vasodilator Nitric oxide (NO). Pulmonary arterial cell cultures treated with fasudil showed a significant increase in eNOS mRNA levels in a dose dependent manner, and the half-life of eNOS mRNA increased 2-folds. These findings suggested that ROCK inhibition with fasudil increases eNOS expression by stabilizing eNOS mRNA, which contributed to an increase of NO level to enhance vasodilation. ## Extracellular signal-regulated kinase(ERK) activity and p27Kip1 levels The proliferative effects of ROCK on vascular endothelial cells is due to the activation of extracellular signal-regulated kinase (ERK). ERK mediates cell proliferation via the phosphorylation of p27Kip1, thus accelerating the degradation rate of p27Kip1. p27Kip1 is a cyclin-dependent kinase (CDK) inhibitor which down-regulates cell cycle by binding cyclin-CDK complex. Human pulmonary arterial smooth muscle cells treated with fasudil showed a decrease in cell proliferation in a dose-dependent manner. Fasudil also decreases ERK activities, as well as increases level of p27Kip1. This suggested that the anti-proliferative effects of fasudil is due to the decrease of ERK activities via the inhibition of ROCK.	Fasudil Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] # Overview Fasudil hydrochloride (INN) is a potent Rho-kinase inhibitor and vasodilator.[1] Since it was discovered, it has been used for the treatment of cerebral vasospasm, which is often due to subarachnoid hemorrhage,[2] as well as to improve the cognitive decline seen in stroke victims. It has been found to be effective for the treatment of pulmonary hypertension.[3] It was demonstrated in February 2009 that fasudil could also be used to enhance memory and improve the prognosis of Alzheimers patients.[4] # Pulmonary Hypertension Pulmonary hypertension (PH) is a cardiovascular disease characterized by a resting mean pulmonary arterial pressure exceeding 25 mmHg, or more than 30 mmHg during exercise.[5] It arises from the pulmonary vascular remodeling accompanied by endothelial dysfunction, fibroblast activation, and endothelial cellular proliferation. Symptoms of PH include shortness of breath, chronic fatigue, dizziness, peripheral edema, cyanosis, and chest pain. If untreated, PH could lead to heart failure and death.[6] PH is divided into 5 classifications: arterial, venous, hypoxemia, thromboembolic, and miscellaneous.[7] # Molecular Mechanism Fasudil (HA-1077) is a selective RhoA/Rho kinase(ROCK) inhibitor.[8] ROCK is an enzyme that plays an important role in mediating vasoconstriction and vascular remodeling in the pathogenesis of PH. ROCK induces vasoconstriction by phosphorylating the myosin-binding subunit of myosin light chain (MLC) phosphatase, thus decreasing MLC phosphatase activity and enhancing vascular smooth muscle contraction.[8] ## Angiotensin-converting Enzyme (ACE) expression and Angiotensin-II (Ang-II) levels ACE is an enzyme that catalyzes the conversion of Angiotensin-I (Ang-I) to Angiotensin-II (Ang-II). Ang-II is a peptide hormone which increases blood pressure by initiating vasoconstriction and aldosterone secretion. ROCK increases ACE expression and activity in PH. By inhibiting ROCK with fasudil, circulating ACE and Ang-II are reduced, leading to a decrease in pulmonary vascular pressure.[9] ## Endothelial Nitric Oxide Synthase (eNOS) expression eNOS mediates the production of the vasodilator Nitric oxide (NO). Pulmonary arterial cell cultures treated with fasudil showed a significant increase in eNOS mRNA levels in a dose dependent manner, and the half-life of eNOS mRNA increased 2-folds. These findings suggested that ROCK inhibition with fasudil increases eNOS expression by stabilizing eNOS mRNA, which contributed to an increase of NO level to enhance vasodilation.[10] ## Extracellular signal-regulated kinase(ERK) activity and p27Kip1 levels The proliferative effects of ROCK on vascular endothelial cells is due to the activation of extracellular signal-regulated kinase (ERK).[11] ERK mediates cell proliferation via the phosphorylation of p27Kip1, thus accelerating the degradation rate of p27Kip1.[12] p27Kip1 is a cyclin-dependent kinase (CDK) inhibitor which down-regulates cell cycle by binding cyclin-CDK complex.[13] Human pulmonary arterial smooth muscle cells treated with fasudil showed a decrease in cell proliferation in a dose-dependent manner. Fasudil also decreases ERK activities, as well as increases level of p27Kip1. This suggested that the anti-proliferative effects of fasudil is due to the decrease of ERK activities via the inhibition of ROCK.[11]	https://www.wikidoc.org/index.php/Fasudil
8aaab77792e6c02439dee8e3bfcfcf40bf71aa12	wikidoc	Feather	Feather Feathers are one of the epidermal growths that form the distinctive outer covering, or plumage, on birds. They are the outstanding characteristic that distinguishes the Class Aves from all other living groups. Other Theropoda also had feathers (see Feathered dinosaurs). # Characteristics Feathers are among the most complex structural organs found in vertebrates: integumentary appendages, formed by controlled proliferation of cells in the epidermis, or outer skin layer, that produce keratin proteins. The β-keratins in feathers, beaks and claws — and the claws, scales and shells of reptiles — are composed of protein strands hydrogen-bonded into β-pleated sheets, which are then further twisted and crosslinked by disulfide bridges into structures even tougher than the α-keratins of mammalian hair, horns and hoof. Feathers insulate birds from water and cold temperatures. The individual feathers in the wings and tail play important roles in controlling flight. These have their own identity and are not just randomly distributed. Some species have a crest of feathers on their heads. Although feathers are light, a bird's plumage weighs two or three times more than its skeleton, since many bones are hollow and contain air sacs. Color patterns serve as camouflage against predators for birds in their habitats, and by predators looking for a meal. As with fish, the top and bottom colors may be different to provide camouflage during flight. Striking differences in feather patterns and colors are part of the sexual dimorphism of many bird species and are particularly important in selection of mating pairs. The remarkable colors and feather sizes of some species have never been fully explained. There are two basic types of feather: vaned feathers which cover the exterior of the body, and down feathers which are underneath the vaned feathers. The pennaceous feathers are vaned feathers. Also called contour feathers, pennaceous feathers are distributed over the whole body. Some of them are modified into remiges, the flight feathers of the wing, and rectrices, the flight feathers of the tail. A typical vaned feather features a main shaft, called the rachis. Fused to the rachis are a series of branches, or barbs; the barbs themselves are also branched and form the barbules. These barbules have minute hooks called barbicels for cross-attachment. Down feathers are fluffy because they lack barbicels, so the barbules float free of each other, allowing the down to trap much air and provide excellent thermal insulation. At the base of the feather, the rachis expands to form the hollow tubular calamus, or quill, which inserts into a follicle in the skin. The Dyck texture is what causes the colors blue and green in most parrots. This is due to a texture effect in microscopic portions of the feather itself, rather than pigment, or the Tyndall effect as was previously believed. The Dyck texture alters color produced by pigment. Thus, an albino parrot will be white. The spectacular red feathers of certain parrots owe their vibrancy to a rare set of pigments found nowhere else in nature. Albinism is a rare lack of pigment in some or all of a bird's feathers. In some birds, the feather colors may be created or altered by uropygial gland secretions. The yellow bill colors of many hornbills are produced by preen gland secretions. Other differences that may only be visible in the ultraviolet region are also possible. A bird's feathers are replaced periodically during its life through molting. New feathers are formed through the same follicle from which the old ones were fledged. Some birds have a supply of powder down feathers which grow continuously, with small particles regularly breaking off from the ends of the barbules. These particles produce a powder that sifts through the feathers on the bird's body and acts as a waterproofing agent and a feather conditioner. Powder down has evolved independently in several taxa and can be found in down as well as pennaceous feathers. They may be scattered in plumage in the pigeons and parrots or in localized patches on the breast, belly or flanks as in herons and frogmouths. Herons use their bill to break the feathers and to spread them while cockatoos may use their head as a powder puff to apply the powder. Waterproofing can be lost by exposure to emulsifying agents due to human pollution. Feathers can become waterlogged and birds may sink. It is also very difficult to clean and rescue birds whose feathers have been fouled by oil spills. Bristles are stiff, tapering feathers with a large rachis but few barbs. Rictal bristles are bristles found around the eyes and bill. They may serve a similar purpose to eyelashes and vibrissae in mammals. It has been suggested that they may aid insectivorous birds in prey capture or that it may have sensory functions, however there is no clear evidence. In one study, Willow Flycatchers (Empidonax traillii) and they were found to catch insects equally well before and after removal of the rictal bristles. Feathers are not uniformly distributed on the skin of the bird except in the Penguin. In most birds the feathers grow from specific tracts of skin called pterylae while there are regions which are free of feathers called apterylae. The arrangement of these feather tracts, pterylosis, varies across bird families. # Evolution Feathers most likely originated as a filamentous insulation structure, or possibly as markers for mating, with flight emerging only as a secondary purpose. It has been thought that feathers evolved from the scales of reptiles, but recent research suggests that while there is a definite relationship between these structures, it remains uncertain of the exact process. (see Quarterly Review of Biology 77:3 (September 2002): 261-95). In experiments where a virus was used to reduce the levels of certain proteins in chicken embryos, the chickens retained webbed feet, and the scutes developed into feathers. The scales, however, did not develop into feathers, and the research suggests that feathers did not evolve from reptilian scales. ## Feathered dinosaurs Several dinosaurs have been discovered with feathers on their limbs that would not have functioned for flight. One theory is that feathers originally developed on dinosaurs as a means of insulation; those small dinosaurs that then grew longer feathers may have found them helpful in gliding, which would have begun the evolutionary process that resulted in some proto-birds like Archaeopteryx and Microraptor zhaoianus. Other dinosaurs discovered with feathers include Pedopenna daohugouensis, Sinosauropteryx, and Dilong paradoxus, a tyrannosauroid which is 60 to 70 million years older than Tyrannosaurus rex. Currently the question is not whether birds are dinosaurs, but whether they are deinonychosaurians or are dromaeosaurids. It has been suggested that Pedopenna is older than Archaeopteryx, however, their age remains doubted by some experts. # Human uses Feathers have a number of utilitarian and cultural and religious uses. ## Utilitarian functions Feathers are both soft and excellent at trapping heat; thus, they are sometimes used in high-class bedding, especially pillows, blankets, and mattresses. They are also used as filling for winter clothing, such as quilted coats and sleeping bags; goose down especially has great loft, the ability to expand from a compressed, stored state to trap large amounts of compartmentalized, insulating air. Bird feathers have long been used for fletching arrows and in the past were used for ink pens. Colorful feathers such as those belonging to pheasants have been used to decorate fishing lures and hats. During the 18th, 19th, and even 20th Centuries a booming international trade in plumes, to satisfy market demand in North America and Europe for extravagant head-dresses as adornment for fashionable women, caused so much destruction (for example, to egret breeding colonies) that a major campaign against it by conservationists caused the fashion to change and the market to collapse. Feathers of large birds (most often geese) have been and are used to make quill pens. The word pen itself is derived from the Latin penna for feather. The French nom-de-plume for pen name has a similar origin. ## Cultural and religious uses Eagle feathers have great cultural and spiritual value to American Indians in the USA and First Nations peoples in Canada as religious objects. In the United States the religious use of eagle and hawk feathers are governed by the eagle feather law (50 CFR 22), a federal law limiting the possession of eagle feathers to certified and enrolled members of federally recognized Native American tribes. Various birds and their plumages serve as cultural icons throughout the world, from the hawk in ancient Egypt to the bald eagle and the turkey in the United States. In Greek mythology, Daedelus the inventor and Icarus tried to escape his prison by attaching feathered wings to his shoulders with wax, which was melted by the Sun.	Feather Feathers are one of the epidermal growths that form the distinctive outer covering, or plumage, on birds. They are the outstanding characteristic that distinguishes the Class Aves from all other living groups. Other Theropoda also had feathers (see Feathered dinosaurs). # Characteristics Feathers are among the most complex structural organs found in vertebrates: integumentary appendages, formed by controlled proliferation of cells in the epidermis, or outer skin layer, that produce keratin proteins. The β-keratins in feathers, beaks and claws — and the claws, scales and shells of reptiles — are composed of protein strands hydrogen-bonded into β-pleated sheets, which are then further twisted and crosslinked by disulfide bridges into structures even tougher than the α-keratins of mammalian hair, horns and hoof. Feathers insulate birds from water and cold temperatures. The individual feathers in the wings and tail play important roles in controlling flight. These have their own identity and are not just randomly distributed. Some species have a crest of feathers on their heads. Although feathers are light, a bird's plumage weighs two or three times more than its skeleton, since many bones are hollow and contain air sacs. Color patterns serve as camouflage against predators for birds in their habitats, and by predators looking for a meal. As with fish, the top and bottom colors may be different to provide camouflage during flight. Striking differences in feather patterns and colors are part of the sexual dimorphism of many bird species and are particularly important in selection of mating pairs. The remarkable colors and feather sizes of some species have never been fully explained. There are two basic types of feather: vaned feathers which cover the exterior of the body, and down feathers which are underneath the vaned feathers. The pennaceous feathers are vaned feathers. Also called contour feathers, pennaceous feathers are distributed over the whole body. Some of them are modified into remiges, the flight feathers of the wing, and rectrices, the flight feathers of the tail. A typical vaned feather features a main shaft, called the rachis. Fused to the rachis are a series of branches, or barbs; the barbs themselves are also branched and form the barbules. These barbules have minute hooks called barbicels for cross-attachment. Down feathers are fluffy because they lack barbicels, so the barbules float free of each other, allowing the down to trap much air and provide excellent thermal insulation. At the base of the feather, the rachis expands to form the hollow tubular calamus, or quill, which inserts into a follicle in the skin. The Dyck texture is what causes the colors blue and green in most parrots. This is due to a texture effect in microscopic portions of the feather itself, rather than pigment, or the Tyndall effect as was previously believed. The Dyck texture alters color produced by pigment. Thus, an albino parrot will be white. The spectacular red feathers of certain parrots owe their vibrancy to a rare set of pigments found nowhere else in nature. Albinism is a rare lack of pigment in some or all of a bird's feathers. In some birds, the feather colors may be created or altered by uropygial gland secretions. The yellow bill colors of many hornbills are produced by preen gland secretions. Other differences that may only be visible in the ultraviolet region are also possible.[1] A bird's feathers are replaced periodically during its life through molting. New feathers are formed through the same follicle from which the old ones were fledged. Some birds have a supply of powder down feathers which grow continuously, with small particles regularly breaking off from the ends of the barbules. These particles produce a powder that sifts through the feathers on the bird's body and acts as a waterproofing agent and a feather conditioner. Powder down has evolved independently in several taxa and can be found in down as well as pennaceous feathers. They may be scattered in plumage in the pigeons and parrots or in localized patches on the breast, belly or flanks as in herons and frogmouths. Herons use their bill to break the feathers and to spread them while cockatoos may use their head as a powder puff to apply the powder.[1] Waterproofing can be lost by exposure to emulsifying agents due to human pollution. Feathers can become waterlogged and birds may sink. It is also very difficult to clean and rescue birds whose feathers have been fouled by oil spills. Bristles are stiff, tapering feathers with a large rachis but few barbs. Rictal bristles are bristles found around the eyes and bill. They may serve a similar purpose to eyelashes and vibrissae in mammals. It has been suggested that they may aid insectivorous birds in prey capture or that it may have sensory functions, however there is no clear evidence.[2] In one study, Willow Flycatchers (Empidonax traillii) and they were found to catch insects equally well before and after removal of the rictal bristles.[3] Feathers are not uniformly distributed on the skin of the bird except in the Penguin. In most birds the feathers grow from specific tracts of skin called pterylae while there are regions which are free of feathers called apterylae. The arrangement of these feather tracts, pterylosis, varies across bird families. # Evolution Feathers most likely originated as a filamentous insulation structure, or possibly as markers for mating, with flight emerging only as a secondary purpose. It has been thought that feathers evolved from the scales of reptiles, but recent research suggests that while there is a definite relationship between these structures, it remains uncertain of the exact process. (see Quarterly Review of Biology 77:3 (September 2002): 261-95). In experiments where a virus was used to reduce the levels of certain proteins in chicken embryos, the chickens retained webbed feet, and the scutes developed into feathers. The scales, however, did not develop into feathers, and the research suggests that feathers did not evolve from reptilian scales. [4] ## Feathered dinosaurs Several dinosaurs have been discovered with feathers on their limbs that would not have functioned for flight. One theory is that feathers originally developed on dinosaurs as a means of insulation; those small dinosaurs that then grew longer feathers may have found them helpful in gliding, which would have begun the evolutionary process that resulted in some proto-birds like Archaeopteryx and Microraptor zhaoianus. Other dinosaurs discovered with feathers include Pedopenna daohugouensis, Sinosauropteryx, and Dilong paradoxus, a tyrannosauroid which is 60 to 70 million years older than Tyrannosaurus rex. Currently the question is not whether birds are dinosaurs, but whether they are deinonychosaurians or are dromaeosaurids. It has been suggested that Pedopenna is older than Archaeopteryx, however, their age remains doubted by some experts. # Human uses Feathers have a number of utilitarian and cultural and religious uses. ## Utilitarian functions Feathers are both soft and excellent at trapping heat; thus, they are sometimes used in high-class bedding, especially pillows, blankets, and mattresses. They are also used as filling for winter clothing, such as quilted coats and sleeping bags; goose down especially has great loft, the ability to expand from a compressed, stored state to trap large amounts of compartmentalized, insulating air. Bird feathers have long been used for fletching arrows and in the past were used for ink pens. Colorful feathers such as those belonging to pheasants have been used to decorate fishing lures and hats. During the 18th, 19th, and even 20th Centuries a booming international trade in plumes, to satisfy market demand in North America and Europe for extravagant head-dresses as adornment for fashionable women, caused so much destruction (for example, to egret breeding colonies) that a major campaign against it by conservationists caused the fashion to change and the market to collapse. Feathers of large birds (most often geese) have been and are used to make quill pens. The word pen itself is derived from the Latin penna for feather.[5] The French nom-de-plume for pen name has a similar origin. ## Cultural and religious uses Eagle feathers have great cultural and spiritual value to American Indians in the USA and First Nations peoples in Canada as religious objects. In the United States the religious use of eagle and hawk feathers are governed by the eagle feather law (50 CFR 22), a federal law limiting the possession of eagle feathers to certified and enrolled members of federally recognized Native American tribes. Various birds and their plumages serve as cultural icons throughout the world, from the hawk in ancient Egypt to the bald eagle and the turkey in the United States. In Greek mythology, Daedelus the inventor and Icarus tried to escape his prison by attaching feathered wings to his shoulders with wax, which was melted by the Sun.	https://www.wikidoc.org/index.php/Feather
d656f6dca7e3934801b47bb54b972b5e9043fb32	wikidoc	Feeling	Feeling # Overview Feeling in psychology is usually reserved for the conscious subjective experience of emotion. Phenomenology and heterophenomenology are philosophical approaches that provide some basis for knowledge of feelings. Many schools of psychotherapy depend on the therapist achieving some kind of understanding of the client's feelings, for which methodologies exist. Some theories of interpersonal relationships also have a role for shared feelings or understanding of another person's feelings. Perception of the physical world does not necessarily result in a universal reaction among receivers (see emotions), but varies depending on one's tendency to handle the situation, how the situation relates to the receiver's past experiences, and any number of other factors. Feelings are also known as a state of consciousness, such as that resulting from emotions, sentiments or desires. # Gut feeling A gut feeling, or gut reaction, is a visceral emotional reaction to something, and often one of uneasiness. Gut feelings are generally regarded as not modulated by conscious thought. "Gut feeling" may also be used as a short-hand term for an individual's "common sense" perception of what is "the right thing to do", such as helping an injured passerby, avoiding dark alleys, and other seemingly instinctive feelings about a given situation. It can also refer to common knowledge that some phrases are true no matter when said, such as "The sky is blue," "Fire is hot," and even individual beliefs in quotation like "Allan loves wally more" and other such statements (which may or may not be true, but to the sayer are more true than anything). Gut feelings, like all reflexive unconscious comparisons, can be re-programmed by practice or experiences.	Feeling Template:Otheruses4 # Overview Feeling in psychology is usually reserved for the conscious subjective experience of emotion.[1] Phenomenology and heterophenomenology are philosophical approaches that provide some basis for knowledge of feelings. Many schools of psychotherapy depend on the therapist achieving some kind of understanding of the client's feelings, for which methodologies exist. Some theories of interpersonal relationships also have a role for shared feelings or understanding of another person's feelings.[citation needed] Perception of the physical world does not necessarily result in a universal reaction among receivers (see emotions), but varies depending on one's tendency to handle the situation, how the situation relates to the receiver's past experiences, and any number of other factors. Feelings are also known as a state of consciousness, such as that resulting from emotions, sentiments or desires. # Gut feeling A gut feeling, or gut reaction, is a visceral emotional reaction to something, and often one of uneasiness. Gut feelings are generally regarded as not modulated by conscious thought. "Gut feeling" may also be used as a short-hand term for an individual's "common sense" perception of what is "the right thing to do", such as helping an injured passerby, avoiding dark alleys, and other seemingly instinctive feelings about a given situation. It can also refer to common knowledge that some phrases are true no matter when said, such as "The sky is blue," "Fire is hot," and even individual beliefs in quotation like "Allan loves wally more" and other such statements (which may or may not be true, but to the sayer are more true than anything). Gut feelings, like all reflexive unconscious comparisons, can be re-programmed by practice or experiences.	https://www.wikidoc.org/index.php/Feeling
1e0811bde45cf43c7671dba36f1dab4835475a12	wikidoc	Urethra	Urethra In anatomy, the urethra is a tube which connects the urinary bladder to the outside of the body. The urethra has an excretory function in both genders to pass urine to the outside, and also a reproductive function in the male, as a passage for sperm. The external urethral sphincter is a striated muscle that allows voluntary control over urination. # Anatomy ## Female urethra In the human female, the urethra is about 1-2 inches long and opens in the vulva between the clitoris and the vaginal opening. Because of the short length of the urethra, women tend to be more susceptible to infections of the bladder (cystitis) and the urinary tract. ## Male urethra In the human male, the urethra is about 8 inches (20 cm) long and opens at the end of the penis. The inside of the urethra has a spiral groove (like rifling in a gun barrel), which makes the urine flow in a wide stream. The urethra is divided into three parts in men, named after the location: The length of a male's urethra, and the fact it contains a number of bends, makes catheterisation more difficult. # Histology The epithelium of the urethra starts off as transitional cells as it exits the bladder. Further along the urethra there are stratified columnar cells, then stratified squamous cells near the external meatus (exit hole). There are small mucus-secreting urethral glands, that help protect the epithelium from the corrosive urine. # Medical problems of the urethra - Hypospadias and epispadias are forms of abnormal development of the urethra in the male, where the opening is not quite where it should be (it occurs lower than normal with hypospadias, and higher with epispadias). In a severe chordee, the urethra can develop between the penis and the scrotum. - Infection of the urethra is urethritis, said to be more common in females than males. Urethritis is a common cause of dysuria (pain when urinating). - Related to urethritis is so called urethral syndrome - Passage of kidney stones through the urethra can be painful and subsequently it can lead to urethral strictures. Endoscopy of the bladder via the urethra is called cystoscopy. # Sexual physiology The male urethra is the conduit for sperm during sexual intercourse. It also serves as a passage for urine to flow.	Urethra Template:Infobox Anatomy Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] In anatomy, the urethra is a tube which connects the urinary bladder to the outside of the body. The urethra has an excretory function in both genders to pass urine to the outside, and also a reproductive function in the male, as a passage for sperm. The external urethral sphincter is a striated muscle that allows voluntary control over urination. # Anatomy ## Female urethra In the human female, the urethra is about 1-2 inches long and opens in the vulva between the clitoris and the vaginal opening. Because of the short length of the urethra, women tend to be more susceptible to infections of the bladder (cystitis) and the urinary tract. ## Male urethra In the human male, the urethra is about 8 inches (20 cm) long and opens at the end of the penis. The inside of the urethra has a spiral groove (like rifling in a gun barrel), which makes the urine flow in a wide stream. The urethra is divided into three parts in men, named after the location: The length of a male's urethra, and the fact it contains a number of bends, makes catheterisation more difficult. # Histology The epithelium of the urethra starts off as transitional cells as it exits the bladder. Further along the urethra there are stratified columnar cells, then stratified squamous cells near the external meatus (exit hole). There are small mucus-secreting urethral glands, that help protect the epithelium from the corrosive urine. # Medical problems of the urethra - Hypospadias and epispadias are forms of abnormal development of the urethra in the male, where the opening is not quite where it should be (it occurs lower than normal with hypospadias, and higher with epispadias). In a severe chordee, the urethra can develop between the penis and the scrotum. - Infection of the urethra is urethritis, said to be more common in females than males. Urethritis is a common cause of dysuria (pain when urinating). - Related to urethritis is so called urethral syndrome - Passage of kidney stones through the urethra can be painful and subsequently it can lead to urethral strictures. Endoscopy of the bladder via the urethra is called cystoscopy. # Sexual physiology The male urethra is the conduit for sperm during sexual intercourse. It also serves as a passage for urine to flow.	https://www.wikidoc.org/index.php/Female_urethra
8f46eb6dfa464c3455fbfd069edd46b36d14e069	wikidoc	Fetendo	Fetendo Fetendo is a form of fetal intervention in the treatment of birth defects and other fetal problems. The procedure uses real-time video imagery from fetoscopy and ultrasonography to guide very small surgical instruments into the uterus in order to surgically help the fetus. The name Fetendo was adopted for the procedure because of how the video-based manipulation recalls a child's video game. # Overview Fetendo intervention is less invasive than open fetal surgery. It can be often be achieved with just a small guided wire sent through a needle-puncture of the skin (percutaneous), though in some cases it may require that a small opening be made in the mother's abdomen. The fact that it is less invasive reduces the mother's postoperative recovery and lessens the troubles with preterm labor. Fetendo has proven to be very useful for some, but not all, fetal conditions. Some examples include: - Twin-twin transfusion syndrome - Laser Ablation of Vessels - Fetal bladder obstructions - Aortic or Pulmonary Valvuloplasty - opening the Aortic or Pulmonary fetal heart valves to allow blood flow - Atrial Septostomy - opening the inter-atrial septum of the fetal heart to allow unrestricted blood flow between the atriums - Congenital diaphragmatic hernia - Balloon tracheal occlusion	Fetendo Fetendo is a form of fetal intervention in the treatment of birth defects and other fetal problems. The procedure uses real-time video imagery from fetoscopy and ultrasonography to guide very small surgical instruments into the uterus in order to surgically help the fetus. The name Fetendo was adopted for the procedure because of how the video-based manipulation recalls a child's video game. # Overview Fetendo intervention is less invasive than open fetal surgery. It can be often be achieved with just a small guided wire sent through a needle-puncture of the skin (percutaneous), though in some cases it may require that a small opening be made in the mother's abdomen. The fact that it is less invasive reduces the mother's postoperative recovery and lessens the troubles with preterm labor. Fetendo has proven to be very useful for some, but not all, fetal conditions. Some examples include: - Twin-twin transfusion syndrome - Laser Ablation of Vessels - Fetal bladder obstructions - Aortic or Pulmonary Valvuloplasty - opening the Aortic or Pulmonary fetal heart valves to allow blood flow - Atrial Septostomy - opening the inter-atrial septum of the fetal heart to allow unrestricted blood flow between the atriums - Congenital diaphragmatic hernia - Balloon tracheal occlusion	https://www.wikidoc.org/index.php/Fetendo
3d976cde6f85bbd0089d7177abdf7f482009feb1	wikidoc	Fewmets	Fewmets # Overview Fewmets is the droppings of an animal, by which the hunter identifies it. It is mentioned in books like The Sword in the Stone by T. H. White. More specifically, it is the dropping of a dragon. (Reference Madeleine L'Engle's A Wind in the Door, and others.) Dragon fewmets are often the source of gunpowder in fantasy novels and role playing games, allowing black powder weapons into the fantasy genre. Fewmets is a Medieval English hunting term, referring to the spoor of a game animal being stalked. The term is derived from the Old English feawa ("scant", hence "few") and metan ("encounter", hence "meet"), with the intimation that these droppings are the only hint of the animal's presence; that the creature itself has yet to be seen. According to T.H. White's novel, the Medieval huntmaster would wrap in leaves the spoor of the animal he was stalking, carrying this package stored in his hunting horn. This part of his job served two vital purposes. Firstly, even if the noble sponsor of the hunt and his equally exalted guests were sufficiently skilled huntsmen to keep up with the hounds, it would have been beneath his dignity to dismount and examine the condition of the spoor to ascertain how close the hunted animal was. He would be shown the excrement, to ascertain from its condition how close the prey might be; but the physical task of retrieving the droppings would be left to the huntmaster—a skilled functionary, but also a commoner. Secondly, in the event that the patron was not knowledgable about woodcraft, the fewmets served as the huntmaster's bona fide. They were physical evidence that there was in fact an animal out there to be caught—and that the sponsor of the event and his noble friends were not being led in a merry and altogether pointless chase around the woods by a malicious or ignorant bumpkin.	Fewmets # Overview Fewmets is the droppings of an animal, by which the hunter identifies it. It is mentioned in books like The Sword in the Stone by T. H. White. More specifically, it is the dropping of a dragon. (Reference Madeleine L'Engle's A Wind in the Door, and others.) Dragon fewmets are often the source of gunpowder in fantasy novels and role playing games, allowing black powder weapons into the fantasy genre. Fewmets is a Medieval English hunting term, referring to the spoor of a game animal being stalked. The term is derived from the Old English feawa ("scant", hence "few") and metan ("encounter", hence "meet"), with the intimation that these droppings are the only hint of the animal's presence; that the creature itself has yet to be seen. According to T.H. White's novel, the Medieval huntmaster would wrap in leaves the spoor of the animal he was stalking, carrying this package stored in his hunting horn. This part of his job served two vital purposes. Firstly, even if the noble sponsor of the hunt and his equally exalted guests were sufficiently skilled huntsmen to keep up with the hounds, it would have been beneath his dignity to dismount and examine the condition of the spoor to ascertain how close the hunted animal was. He would be shown the excrement, to ascertain from its condition how close the prey might be; but the physical task of retrieving the droppings would be left to the huntmaster—a skilled functionary, but also a commoner. Secondly, in the event that the patron was not knowledgable about woodcraft, the fewmets served as the huntmaster's bona fide. They were physical evidence that there was in fact an animal out there to be caught—and that the sponsor of the event and his noble friends were not being led in a merry and altogether pointless chase around the woods by a malicious or ignorant bumpkin. Template:WH Template:WikiDoc Sources	https://www.wikidoc.org/index.php/Fewmets
ac5f302c9a84c74a4cc6f0fd3dd0ed675325551e	wikidoc	Fibrate	Fibrate # Overview In pharmacology, the fibrates are a class of amphipathic carboxylic acids. They are used for a range of metabolic disorders, mainly hypercholesterolemia (high cholesterol), and are therefore hypolipidemic agents. # Members Fibrates prescribed commonly are: - Bezafibrate (e.g. Bezalip®, available in Europe not approved in USA) - Ciprofibrate (e.g. Modalim®, available in Europe not approved in USA) - Clofibrate (largely obsolete due to side-effect profile, e.g. gallstones) - Gemfibrozil (e.g. Lopid®, available in USA) - Fenofibrate (e.g. TriCor®, available in USA) Fenofibric acid (Trilipix) is FDA approved for combination use with statin, in patients with mixed dyslipidemia. # Indications Fibrates are used as accessory therapy in many forms of hypercholesterolemia, usually in combination with statins. Trials do support its use as monotherapy. Although less effective in lowering LDL, fibrates improve HDL and triglyceride levels, and seem to improve insulin resistance when the dyslipidemia is associated with other features of Syndrome X (hypertension and diabetes mellitus type 2). # Doses Different doses of fenofibrate are available in the markets. The standard adult dose is usually >100 mg/day. However, dose lowering is required for patients with renal insufficiency (creatinine clearance < 80). Clinical trials are required to prove the relative efficacy of the different doses of fibrates. # Side effects - Mild stomach upset - Myopathy (muscle pain with CPK elevations). - In combination with statin drugs, fibrates cause an increased risk of rhabdomyolysis (idiosyncratic destruction of muscle tissue, leading to renal failure). A powerful statin drug, cerivastatin (Lipobay®), was withdrawn because of this complication. The less lipophilic statins are less prone to cause this reaction, and are probably safer when combined with fibrates. - Clofibrate are no longer used because they were found to increase morbidity and mortality rates. Also, increased rates of malignancy in rodents have been found. - Fibrates are excreted via kidney. It can cause reversible increases in serum creatinine levels. Thus, reduction in doses are indicated in cases with increased serum creatinine levels. Gemfibrozil's excretion is independent of renal function, and can be used in patients with chronic kidney disease. # Pharmacology Although used clinically since the early 1970s, the mechanism of action of fibrates remained unelucidated until, in the 1990s, it was discovered that fibrates activate PPAR (peroxisome proliferator-activated receptors), especially PPARα. The PPARs are a class of intracellular receptors that modulate carbohydrate, fat metabolism and adipose tissue differentiation. Activation of PPARs causes transcription of a number of genes on the DNA that facilitate lipid metabolism. Fibrates are structurally and pharmacologically related to the thiazolidinediones, a novel class of anti-diabetic drugs that also act on PPARs (more specifically PPARγ)	Fibrate Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] # Overview In pharmacology, the fibrates are a class of amphipathic carboxylic acids. They are used for a range of metabolic disorders, mainly hypercholesterolemia (high cholesterol), and are therefore hypolipidemic agents. # Members Fibrates prescribed commonly are: - Bezafibrate (e.g. Bezalip®, available in Europe not approved in USA) - Ciprofibrate (e.g. Modalim®, available in Europe not approved in USA) - Clofibrate (largely obsolete due to side-effect profile, e.g. gallstones) - Gemfibrozil (e.g. Lopid®, available in USA) - Fenofibrate (e.g. TriCor®, available in USA) Fenofibric acid (Trilipix) is FDA approved for combination use with statin, in patients with mixed dyslipidemia. # Indications Fibrates are used as accessory therapy in many forms of hypercholesterolemia, usually in combination with statins. Trials do support its use as monotherapy. Although less effective in lowering LDL, fibrates improve HDL and triglyceride levels, and seem to improve insulin resistance when the dyslipidemia is associated with other features of Syndrome X (hypertension and diabetes mellitus type 2). # Doses Different doses of fenofibrate are available in the markets. The standard adult dose is usually >100 mg/day. However, dose lowering is required for patients with renal insufficiency (creatinine clearance < 80). Clinical trials are required to prove the relative efficacy of the different doses of fibrates. # Side effects - Mild stomach upset - Myopathy (muscle pain with CPK elevations). - In combination with statin drugs, fibrates cause an increased risk of rhabdomyolysis (idiosyncratic destruction of muscle tissue, leading to renal failure). A powerful statin drug, cerivastatin (Lipobay®), was withdrawn because of this complication. The less lipophilic statins are less prone to cause this reaction, and are probably safer when combined with fibrates. - Clofibrate are no longer used because they were found to increase morbidity and mortality rates. Also, increased rates of malignancy in rodents have been found. - Fibrates are excreted via kidney. It can cause reversible increases in serum creatinine levels. Thus, reduction in doses are indicated in cases with increased serum creatinine levels. Gemfibrozil's excretion is independent of renal function, and can be used in patients with chronic kidney disease. # Pharmacology Although used clinically since the early 1970s, the mechanism of action of fibrates remained unelucidated until, in the 1990s, it was discovered that fibrates activate PPAR (peroxisome proliferator-activated receptors), especially PPARα. The PPARs are a class of intracellular receptors that modulate carbohydrate, fat metabolism and adipose tissue differentiation. Activation of PPARs causes transcription of a number of genes on the DNA that facilitate lipid metabolism. Fibrates are structurally and pharmacologically related to the thiazolidinediones, a novel class of anti-diabetic drugs that also act on PPARs (more specifically PPARγ)	https://www.wikidoc.org/index.php/Fibrate
5be318bce3e777a7e106ddc6cf800c0858b49812	wikidoc	Fibroid	Fibroid Fibroid is a term used for two different types of tumors: - Fibroids is the common term for Leiomyoma originating in the uterus. It is a benign neoplasm composed of smooth muscle cells. - A fibroid tumor is another name for a fibroma, a tumor of fibrous connective tissue.	Fibroid Fibroid is a term used for two different types of tumors: - Fibroids is the common term for Leiomyoma originating in the uterus. It is a benign neoplasm composed of smooth muscle cells. - A fibroid tumor is another name for a fibroma, a tumor of fibrous connective tissue. Template:Disambig Template:WS	https://www.wikidoc.org/index.php/Fibroid
b47cc7fbb9a4fe8ff5644137f146f86f73d4e120	wikidoc	Filipin	Filipin Filipin was isolated by chemists at the Upjohn company in 1955 from the mycelium and culture filtrates of a previously unknown actinomycete, Streptomyces filipinensis, that was discovered in a soil sample collected in the Philippine Islands. Thus the name Filipin. The isolate possessed potent antifungal activity. It was identified as a polyene macrolide based on its characteristic UV-Vis and IR spectra. # Functions Although the polyene macrolide antibiotics exhibit potent antifungal activity, most are too toxic for therapeutic applications, with the exceptions of amphotericin B and nystatin A1. Unlike amphotericin B and nystatin A1 which form sterol-dependent ion channels, filipin is thought to be a simple membrane disrupter. Since Filipin is highly fluorescent and binds specifically to cholesterol it has found widespread use as a histochemical stain for cholesterol. This method of detecting cholesterol in cell membranes is used clinically in the study and diagnosis of Type C Niemann-Pick disease. It is also used in cellular biology as an inhibitor of the raft/caveolae endocytosis pathway on mamallian cells (at concentrations around 3 µg/mL) # Types Filipin is a mixture of four components - filipin I (4%), II (25%), III (53%), and IV (18%) - and should be referred to as the filipin complex. - The major component, filipin III, has the structure which was proposed by Ceder and Ryhage for the filipin complex. - Filipin I, which has been difficult to characterize, is probably a mixture of several components each having two hydroxyl groups fewer than filipin III. - Mass spectroscopy and NMR data indicate that Filipin II is 1'-deoxy-filipin III. - Filipin IV is isomeric to filipin III. Their NMR spectra are nearly identical with the major difference being the splitting pattern of the proton at C2. This indicates that filipin IV is probably epimeric to filipin III at either C1' or C3. The relative and absolute stereochemistry of filipin III was determined by 13C NMR acetonide analysis.	Filipin Filipin was isolated by chemists at the Upjohn company in 1955 from the mycelium and culture filtrates of a previously unknown actinomycete, Streptomyces filipinensis, that was discovered in a soil sample collected in the Philippine Islands. Thus the name Filipin. The isolate possessed potent antifungal activity. It was identified as a polyene macrolide based on its characteristic UV-Vis and IR spectra. # Functions Although the polyene macrolide antibiotics exhibit potent antifungal activity, most are too toxic for therapeutic applications, with the exceptions of amphotericin B and nystatin A1. Unlike amphotericin B and nystatin A1 which form sterol-dependent ion channels, filipin is thought to be a simple membrane disrupter. Since Filipin is highly fluorescent and binds specifically to cholesterol it has found widespread use as a histochemical stain for cholesterol. This method of detecting cholesterol in cell membranes is used clinically in the study and diagnosis of Type C Niemann-Pick disease. It is also used in cellular biology as an inhibitor of the raft/caveolae endocytosis pathway on mamallian cells (at concentrations around 3 µg/mL) # Types Filipin is a mixture of four components - filipin I (4%), II (25%), III (53%), and IV (18%) - and should be referred to as the filipin complex. - The major component, filipin III, has the structure which was proposed by Ceder and Ryhage for the filipin complex. - Filipin I, which has been difficult to characterize, is probably a mixture of several components each having two hydroxyl groups fewer than filipin III. - Mass spectroscopy and NMR data indicate that Filipin II is 1'-deoxy-filipin III. - Filipin IV is isomeric to filipin III. Their NMR spectra are nearly identical with the major difference being the splitting pattern of the proton at C2. This indicates that filipin IV is probably epimeric to filipin III at either C1' or C3. The relative and absolute stereochemistry of filipin III was determined by 13C NMR acetonide analysis.	https://www.wikidoc.org/index.php/Filipin
ca24b34ee96711096c57cbde727645aadd0fa1f7	wikidoc	Fimbrin	Fimbrin Fimbrin also known as is plastin 1 is a protein that in humans is encoded by the PLS1 gene. Fimbrin is an actin cross-linking protein important in the formation of filopodia. # Structure Fimbrin belongs to the calponin homology (CH) domain superfamily of actin cross-linking proteins. Like other members of this superfamily, which include α-actinin, β-spectrin, dystrophin, ABP-120 and filamin, it has a conserved 27 kDa actin-binding domain that contains a tandem duplication of a sequence that is homologous to calponin. In addition to cross-linking actin filaments into bundles and networks, CH domains also bind intermediate filaments and some signal transduction proteins to the actin cytoskeleton. Structural comparison of actin filaments and fimbrin CH domain-decorated actin filaments has revealed changes in the actin structure due to fimbrin-mediated cross-linking that may affect the actin filaments' affinity for other actin-binding proteins and may be part of the regulation of the cytoskeleton itself. In humans, three highly homologous, strictly tissue and locale specific isoforms have been identified: I-, T- and L-fimbrin. L-fimbrin is found in only normal or transformed leukocytes where it becomes phosphorylated in response to other factors such as interleukin-1. I-fimbrin is expressed by intestine and kidney epithelial cells. T-fimbrin is found in epithelial and mesenchymal cells derived from solid tissue where it does not become phosphorylated. Differences in expression, sequence and phosphorylation among the various fimbrin isoforms suggest the likelihood of functional differences. # Function Fimbrin is present in several distinct structures in different cell types, including intestinal microvilli, hair cell stereocilia and fibroblast filopodia. It is usually associated with polarized actin filaments in membrane ruffles, filopodia, stereocilia and adhesion plaques. Sequence homology and biochemical properties show that fimbrin is highly conserved from yeast to humans. Yeast mutants lacking fimbrin are defective in morphogenesis and endocytosis. Owing to the close proximity of its tandem actin-binding domains, fimbrin directs the formation of tightly bundled actin filaments that participate in dynamic processes, including cytokinesis in yeast and host cell invasion by enteropathic bacteria. Although fimbrin's involvement in processes like these as well as its role in assembly and regulation of microfilament networks are well documented, there are fewer experimental data describing the overall domain organization of the molecule. Klein et al. (2004) detailed the crystal structure of the Arabidopsis thaliana and Schizosaccharomyces pombe fimbrin cores in an attempt to highlight the compact and distinctly asymmetric organization of the fimbrin molecule. This structural study of the fimbrin core represents the first detailed structural description of a functional actin cross-linking protein.	Fimbrin Fimbrin also known as is plastin 1 is a protein that in humans is encoded by the PLS1 gene.[1] Fimbrin is an actin cross-linking protein important in the formation of filopodia. # Structure Fimbrin belongs to the calponin homology (CH) domain superfamily of actin cross-linking proteins. Like other members of this superfamily, which include α-actinin, β-spectrin, dystrophin, ABP-120 and filamin, it has a conserved 27 kDa actin-binding domain that contains a tandem duplication of a sequence that is homologous to calponin. In addition to cross-linking actin filaments into bundles and networks, CH domains also bind intermediate filaments and some signal transduction proteins to the actin cytoskeleton. Structural comparison of actin filaments and fimbrin CH domain-decorated actin filaments has revealed changes in the actin structure due to fimbrin-mediated cross-linking that may affect the actin filaments' affinity for other actin-binding proteins and may be part of the regulation of the cytoskeleton itself.[2] In humans, three highly homologous, strictly tissue and locale specific isoforms have been identified: I-, T- and L-fimbrin.[2] L-fimbrin is found in only normal or transformed leukocytes where it becomes phosphorylated in response to other factors such as interleukin-1. I-fimbrin is expressed by intestine and kidney epithelial cells.[3] T-fimbrin is found in epithelial and mesenchymal cells derived from solid tissue where it does not become phosphorylated. Differences in expression, sequence and phosphorylation among the various fimbrin isoforms suggest the likelihood of functional differences.[3] # Function Fimbrin is present in several distinct structures in different cell types, including intestinal microvilli, hair cell stereocilia and fibroblast filopodia.[3] It is usually associated with polarized actin filaments in membrane ruffles, filopodia, stereocilia and adhesion plaques. Sequence homology and biochemical properties show that fimbrin is highly conserved from yeast to humans. Yeast mutants lacking fimbrin are defective in morphogenesis and endocytosis.[2] Owing to the close proximity of its tandem actin-binding domains, fimbrin directs the formation of tightly bundled actin filaments that participate in dynamic processes, including cytokinesis in yeast and host cell invasion by enteropathic bacteria. Although fimbrin's involvement in processes like these as well as its role in assembly and regulation of microfilament networks are well documented, there are fewer experimental data describing the overall domain organization of the molecule. Klein et al. (2004) detailed the crystal structure of the Arabidopsis thaliana and Schizosaccharomyces pombe fimbrin cores in an attempt to highlight the compact and distinctly asymmetric organization of the fimbrin molecule. This structural study of the fimbrin core represents the first detailed structural description of a functional actin cross-linking protein.[4]	https://www.wikidoc.org/index.php/Fimbrin
b28b92d8e626c4b3dc15de85f798c340076f7c73	wikidoc	Fissile	Fissile In nuclear engineering, a fissile material is one that is capable of sustaining a chain reaction of nuclear fission. All known fissile materials are capable of sustaining a chain reaction in which either thermal or slow neutrons or fast neutrons predominate. That is, they can all be used to fuel: - A thermal reactor, with a neutron moderator - A fast reactor, with no moderator - A nuclear explosive # Fissile vs fissionable "Fissile" is distinguished from "fissionable". "Fissionable" are any materials with atoms that can undergo nuclear fission. "Fissile" is defined to be materials that are fissionable by neutrons with zero kinetic energy. "Fissile" thus, is more restrictive than "fissionable" — although all fissile materials are fissionable, not all fissionable materials are fissile. Some authorities even restrict the term fissionable to mean only non-fissile materials. Notably, uranium-238 is fissionable but not fissile. Neutrons produced by fission of e.g. U-235 have an energy of ca. 1 MeV (100 TJ/kg, i.e. a speed of 14,000 km/s) and do not cause fission of U-238, but neutrons produced by deuterium-tritium fusion have an energy of 14.1 MeV neutrons (1400 TJ/kg, i.e. a speed of 52,000 km/s) and can easily fission uranium-238 and other non-fissile actinides. The neutrons produced by this fission are again not fast enough to produce new fissions, so U-238 does not sustain a chain reaction. Fast fission of uranium-238 in the third stage of the fission-fusion-fission weapons contributes greatly to their yield and fallout. Fast fission of uranium-238 also makes a significant contribution to the power output of some fast breeder reactors. # Fissile nuclides Fissile nuclides in nuclear fuels include: - Uranium-235 which occurs in natural uranium and enriched uranium - Plutonium-239 bred from Uranium-238 by neutron capture - Plutonium-241 bred from Plutonium-240 by neutron capture - Uranium-233 bred from Thorium-232 by neutron capture In general, actinide isotopes with an odd number of neutrons are fissile. Most nuclear fuels have odd N (number of protons and neutrons) and even Z (number of protons). Isotopes with an odd number of neutrons and odd number of protons (odd Z, even N) are shortlived because they can beta decay to an isotope with an even number of neutrons and even number of protons. (even Z, even N) Fissile nuclides do not have a 100% chance of fissioning on absorption of a neutron. The chance is dependent on the nuclide as well as neutron energy. For low and medium-energy neutrons, the cross sections for fission and for capture emitting a gamma ray, and the percentage of nonfissions are: # Nuclear fuel To be a useful fuel for nuclear fission chain reactions, the material must: - Be in the region of the binding energy curve where a fission chain reaction is possible (i.e. above radium) - Have a high probability of fission on neutron capture - Release two or more neutrons on average per neutron capture (which means an even higher number on each fission, to compensate for nonfissions) - Have a reasonably long half life - Be available in suitable quantities # Legal controls The International Atomic Energy Agency used to categorize fissile materials according to their security requirements for transportation: - Fissile Class I: no controls - Fissile Class II: limits on amount of materials shipped - Fissile Class III: special shipping arrangements are needed but these classes were replaced in the mid 1990s.	Fissile Template:Otheruses4 In nuclear engineering, a fissile material is one that is capable of sustaining a chain reaction of nuclear fission. All known fissile materials are capable of sustaining a chain reaction in which either thermal or slow neutrons or fast neutrons predominate. That is, they can all be used to fuel: - A thermal reactor, with a neutron moderator - A fast reactor, with no moderator - A nuclear explosive # Fissile vs fissionable "Fissile" is distinguished from "fissionable". "Fissionable" are any materials with atoms that can undergo nuclear fission. "Fissile" is defined to be materials that are fissionable by neutrons with zero kinetic energy. "Fissile" thus, is more restrictive than "fissionable" — although all fissile materials are fissionable, not all fissionable materials are fissile. Some authorities even restrict the term fissionable to mean only non-fissile materials. Notably, uranium-238 is fissionable but not fissile. Neutrons produced by fission of e.g. U-235 have an energy of ca. 1 MeV (100 TJ/kg, i.e. a speed of 14,000 km/s) and do not cause fission of U-238, but neutrons produced by deuterium-tritium fusion have an energy of 14.1 MeV neutrons (1400 TJ/kg, i.e. a speed of 52,000 km/s) and can easily fission uranium-238 and other non-fissile actinides. The neutrons produced by this fission are again not fast enough to produce new fissions, so U-238 does not sustain a chain reaction. Fast fission of uranium-238 in the third stage of the fission-fusion-fission weapons contributes greatly to their yield and fallout. Fast fission of uranium-238 also makes a significant contribution to the power output of some fast breeder reactors. # Fissile nuclides Fissile nuclides in nuclear fuels include: - Uranium-235 which occurs in natural uranium and enriched uranium - Plutonium-239 bred from Uranium-238 by neutron capture - Plutonium-241 bred from Plutonium-240 by neutron capture - Uranium-233 bred from Thorium-232 by neutron capture In general, actinide isotopes with an odd number of neutrons are fissile. Most nuclear fuels have odd N (number of protons and neutrons) and even Z (number of protons). Isotopes with an odd number of neutrons and odd number of protons (odd Z, even N) are shortlived because they can beta decay to an isotope with an even number of neutrons and even number of protons. (even Z, even N) Fissile nuclides do not have a 100% chance of fissioning on absorption of a neutron. The chance is dependent on the nuclide as well as neutron energy. For low and medium-energy neutrons, the cross sections for fission and for capture emitting a gamma ray, and the percentage of nonfissions are: # Nuclear fuel To be a useful fuel for nuclear fission chain reactions, the material must: - Be in the region of the binding energy curve where a fission chain reaction is possible (i.e. above radium) - Have a high probability of fission on neutron capture - Release two or more neutrons on average per neutron capture (which means an even higher number on each fission, to compensate for nonfissions) - Have a reasonably long half life - Be available in suitable quantities # Legal controls The International Atomic Energy Agency used to categorize fissile materials according to their security requirements for transportation:[1][2] - Fissile Class I: no controls - Fissile Class II: limits on amount of materials shipped - Fissile Class III: special shipping arrangements are needed but these classes were replaced in the mid 1990s.[3]	https://www.wikidoc.org/index.php/Fissile
bb7d565a4399d2947b3e4617235d5539348a3721	wikidoc	Fissure	Fissure In anatomy, fissure (Latin fissura, Plural fissurae) is a groove, natural division, deep furrow, cleft, or tear in various parts of the body. # Natural fissure Various types of fissure are: - Auricular fissure: found in the temporal bone - Fissure of Bichat: found below the corpus callosum in the cerebellum of the brain. - Broca's fissure: found in the third left frontal fold of the brain. - Burdach's fissure: connects the brain's insula and the inner surface of the operculum. - Calcarine fissure: extends from the occipital of the cerebrum to the occipital fissure. - Callosomarginal fissure: found in the mesial surface of the cerebrum. - Central fissure or Ronaldo's fissure: separates the brain's frontal and parietal lobes. - Clevenger's fissure: found in the inferior temporal lobe of the brain - Collateral fissure: found in the inferior surface of the cerebrum. - Fissure vent: a volcanic vent that does not include explosive activity. - Henle's fissure: the connective tissue between the muscle fibers of the heart. - Hippocampal fissure: a fissure that extends from the brain's corpus callosum to the tip of the temporal lobe. - Horizontal fissure or Transverse fissure: found between the cerebrum and the cerebellum. Transverse fissure is also found in the liver and lungs. - Longitudinal fissure: found in the lower surface of the liver, also a fissure that separates the right and left hemispheres of the cerebrum. - Occipitoparietal fissure: found between the occipital and parietal lobes of the brain. - Palpebral fissure: separates the upper and lower eyelids. - Portal fissure: found in the under-surface of the liver. - Sphenoidal fissure: separates the wings and the body of the sphenoid bone. - Fissure of Sylvius: separates the frontal and parietal lobes of the brain from the temporal lobe. - Umbilical fissure: found in front of the liver. - Wernicke's fissure: separates the brain's temporal and parietal lobes from the occipital lobe. - Zygal fissure: found in the cerebrum. # Abnormal fissure Fissure can also mean unnatural tract or ulcer, most commonly found in the anus. One of the most common types of fissure is anal fissure.	Fissure Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] In anatomy, fissure (Latin fissura, Plural fissurae) is a groove, natural division, deep furrow, cleft, or tear in various parts of the body. # Natural fissure Various types of fissure are: - Auricular fissure: found in the temporal bone - Fissure of Bichat: found below the corpus callosum in the cerebellum of the brain. - Broca's fissure: found in the third left frontal fold of the brain. - Burdach's fissure: connects the brain's insula and the inner surface of the operculum. - Calcarine fissure: extends from the occipital of the cerebrum to the occipital fissure. - Callosomarginal fissure: found in the mesial surface of the cerebrum. - Central fissure or Ronaldo's fissure: separates the brain's frontal and parietal lobes. - Clevenger's fissure: found in the inferior temporal lobe of the brain - Collateral fissure: found in the inferior surface of the cerebrum. - Fissure vent: a volcanic vent that does not include explosive activity. - Henle's fissure: the connective tissue between the muscle fibers of the heart. - Hippocampal fissure: a fissure that extends from the brain's corpus callosum to the tip of the temporal lobe. - Horizontal fissure or Transverse fissure: found between the cerebrum and the cerebellum. Transverse fissure is also found in the liver and lungs. - Longitudinal fissure: found in the lower surface of the liver, also a fissure that separates the right and left hemispheres of the cerebrum. - Occipitoparietal fissure: found between the occipital and parietal lobes of the brain. - Palpebral fissure: separates the upper and lower eyelids. - Portal fissure: found in the under-surface of the liver. - Sphenoidal fissure: separates the wings and the body of the sphenoid bone. - Fissure of Sylvius: separates the frontal and parietal lobes of the brain from the temporal lobe. - Umbilical fissure: found in front of the liver. - Wernicke's fissure: separates the brain's temporal and parietal lobes from the occipital lobe. - Zygal fissure: found in the cerebrum. # Abnormal fissure Fissure can also mean unnatural tract or ulcer, most commonly found in the anus. One of the most common types of fissure is anal fissure.	https://www.wikidoc.org/index.php/Fissure
80f5a213483052dadc7137b417920a0f8ca33046	wikidoc	Flaccid	Flaccid Flaccid is a term used in medicine to refer to an object that is soft, or not tense. In the context of of muscles, it is a near synonym for hypotonia. It can also be used to describe certain types of paralysis (such as flaccid paralysis), as a contrast to spastic paralysis. It can also be used to describe other tissues, such as the labia. The medical meaning of the term is sometimes used in other contexts, to describe objects or actions which are weak or ineffectual.	Flaccid Flaccid is a term used in medicine to refer to an object that is soft, or not tense. In the context of of muscles, it is a near synonym for hypotonia. It can also be used to describe certain types of paralysis (such as flaccid paralysis), as a contrast to spastic paralysis. It can also be used to describe other tissues, such as the labia. The medical meaning of the term is sometimes used in other contexts, to describe objects or actions which are weak or ineffectual. # External links - Template:EMedicineDictionary Template:WH Template:WikiDoc Sources	https://www.wikidoc.org/index.php/Flaccid
ba15ec47efe88e575bb40eb0cf405b337eb655bc	wikidoc	Flexion	Flexion # Overview In anatomy, flexion is a position that is made possible by the joint angle decreasing. The skeletal (bones, cartilage, and ligaments) and muscular (muscles and tendons) systems work together to move the joint into a "flexed" position. For example the elbow is flexed when the hand is brought closer to the shoulder. The trunk may be flexed toward the legs or the neck to the chest. The opposite term is extension, or straightening. Flexion decreases the angle between the bones of the limb at a joint, and extension increases it. Note that specific flexion activities may occur only along the sagittal plane, i.e. from the forward to backward direction, and not side-to-side direction, which is further discussed in abduction. # Exercises Active range of motion exercises include movements such as flexion and extension. These exercises are used after an injury or surgery. They are done by a physical therapist or nurse initially, and may be continued by the patient. In the healing process, active range of motion exercises, should avoid forcing the appendage into the extension or flexion position. The stress induced may re-injure the affected appendage (limb). # Muscles of flexion ## Upper limb - of arm, at shoulder Anterior compartment of the arm Coracobrachialis Biceps brachii - Anterior compartment of the arm Coracobrachialis Biceps brachii - Coracobrachialis - Biceps brachii - of forearm, at elbow Anterior compartment of the arm Biceps brachii Brachialis Brachioradialis Anterior compartment of the forearm Pronator teres Flexor carpi radialis Palmaris longus Flexor carpi ulnaris Flexor digitorum superficialis - Anterior compartment of the arm Biceps brachii Brachialis Brachioradialis - Biceps brachii - Brachialis - Brachioradialis - Anterior compartment of the forearm Pronator teres Flexor carpi radialis Palmaris longus Flexor carpi ulnaris Flexor digitorum superficialis - Pronator teres - Flexor carpi radialis - Palmaris longus - Flexor carpi ulnaris - Flexor digitorum superficialis - of hand, at wrist Anterior compartment of the forearm Flexor carpi radialis Palmaris longus Flexor carpi ulnaris Flexor digitorum superficialis Flexor digitorum profundus - Anterior compartment of the forearm Flexor carpi radialis Palmaris longus Flexor carpi ulnaris Flexor digitorum superficialis Flexor digitorum profundus - Flexor carpi radialis - Palmaris longus - Flexor carpi ulnaris - Flexor digitorum superficialis - Flexor digitorum profundus - of proximal phalanges, at metacarpophalangeal joint Lumbricals of the hand Dorsal interossei of the hand Palmar interossei Flexor digiti minimi brevis (little finger only) - Lumbricals of the hand - Dorsal interossei of the hand - Palmar interossei - Flexor digiti minimi brevis (little finger only) - of intermediate phalanges, at proximal interphalangeal joints Flexor digitorum superficialis - Flexor digitorum superficialis - of distal phalanges, at distal interphalangeal joints Flexor digitorum profundus - Flexor digitorum profundus - of thumb Flexor pollicis longus Flexor pollicis brevis - Flexor pollicis longus - Flexor pollicis brevis ## Lower limb - of femur/thigh at hip (L1-L2) Iliopsoas Tensor fasciae latae Rectus femoris (additional minor contributions from other hip flexors) - Iliopsoas - Tensor fasciae latae - Rectus femoris - (additional minor contributions from other hip flexors) - of leg at knee (L5-S2) Posterior compartment of thigh/Hamstrings Biceps femoris Semitendinosus Semimembranosus Gracilis Sartorius Tensor fasciae latae Gastrocnemius Popliteus Plantaris (negligible) - Posterior compartment of thigh/Hamstrings Biceps femoris Semitendinosus Semimembranosus - Biceps femoris - Semitendinosus - Semimembranosus - Gracilis - Sartorius - Tensor fasciae latae - Gastrocnemius - Popliteus - Plantaris (negligible) - of toes Posterior compartment of leg Flexor hallucis longus Flexor digitorum longus Flexor digitorum brevis Quadratus plantae Flexor hallucis brevis Flexor digiti minimi brevis - Posterior compartment of leg Flexor hallucis longus Flexor digitorum longus - Flexor hallucis longus - Flexor digitorum longus - Flexor digitorum brevis - Quadratus plantae - Flexor hallucis brevis - Flexor digiti minimi brevis - of proximal phalanges at metatarsophalangeal joint Lumbrical muscle (foot) Plantar interossei Dorsal interossei - Lumbrical muscle (foot) - Plantar interossei - Dorsal interossei ## Other - torso/lumbar vertebrae Rectus abdominis muscle - Rectus abdominis muscle - neck at atlanto-occipital joint Longus capitis muscle - Longus capitis muscle	Flexion Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] # Overview In anatomy, flexion is a position that is made possible by the joint angle decreasing. The skeletal (bones, cartilage, and ligaments) and muscular (muscles and tendons) systems work together to move the joint into a "flexed" position. For example the elbow is flexed when the hand is brought closer to the shoulder. The trunk may be flexed toward the legs or the neck to the chest. The opposite term is extension, or straightening. Flexion decreases the angle between the bones of the limb at a joint, and extension increases it. Note that specific flexion activities may occur only along the sagittal plane, i.e. from the forward to backward direction, and not side-to-side direction, which is further discussed in abduction. # Exercises Active range of motion exercises include movements such as flexion and extension. These exercises are used after an injury or surgery. They are done by a physical therapist or nurse initially, and may be continued by the patient. In the healing process, active range of motion exercises, should avoid forcing the appendage into the extension or flexion position. The stress induced may re-injure the affected appendage (limb). # Muscles of flexion ## Upper limb - of arm, at shoulder[1] Anterior compartment of the arm Coracobrachialis Biceps brachii - Anterior compartment of the arm Coracobrachialis Biceps brachii - Coracobrachialis - Biceps brachii - of forearm, at elbow[2] Anterior compartment of the arm Biceps brachii Brachialis Brachioradialis Anterior compartment of the forearm Pronator teres Flexor carpi radialis Palmaris longus Flexor carpi ulnaris Flexor digitorum superficialis - Anterior compartment of the arm Biceps brachii Brachialis Brachioradialis - Biceps brachii - Brachialis - Brachioradialis - Anterior compartment of the forearm Pronator teres Flexor carpi radialis Palmaris longus Flexor carpi ulnaris Flexor digitorum superficialis - Pronator teres - Flexor carpi radialis - Palmaris longus - Flexor carpi ulnaris - Flexor digitorum superficialis - of hand, at wrist[3] Anterior compartment of the forearm Flexor carpi radialis Palmaris longus Flexor carpi ulnaris Flexor digitorum superficialis Flexor digitorum profundus - Anterior compartment of the forearm Flexor carpi radialis Palmaris longus Flexor carpi ulnaris Flexor digitorum superficialis Flexor digitorum profundus - Flexor carpi radialis - Palmaris longus - Flexor carpi ulnaris - Flexor digitorum superficialis - Flexor digitorum profundus - of proximal phalanges, at metacarpophalangeal joint [4] Lumbricals of the hand Dorsal interossei of the hand Palmar interossei Flexor digiti minimi brevis (little finger only) - Lumbricals of the hand - Dorsal interossei of the hand - Palmar interossei - Flexor digiti minimi brevis (little finger only) - of intermediate phalanges, at proximal interphalangeal joints [5] Flexor digitorum superficialis - Flexor digitorum superficialis - of distal phalanges, at distal interphalangeal joints Flexor digitorum profundus - Flexor digitorum profundus - of thumb[6][7] Flexor pollicis longus Flexor pollicis brevis - Flexor pollicis longus - Flexor pollicis brevis ## Lower limb - of femur/thigh at hip (L1-L2)[8] Iliopsoas Tensor fasciae latae Rectus femoris (additional minor contributions from other hip flexors) - Iliopsoas - Tensor fasciae latae - Rectus femoris - (additional minor contributions from other hip flexors) - of leg at knee (L5-S2)[9] Posterior compartment of thigh/Hamstrings Biceps femoris Semitendinosus Semimembranosus Gracilis Sartorius Tensor fasciae latae Gastrocnemius Popliteus Plantaris (negligible) - Posterior compartment of thigh/Hamstrings Biceps femoris Semitendinosus Semimembranosus - Biceps femoris - Semitendinosus - Semimembranosus - Gracilis - Sartorius - Tensor fasciae latae - Gastrocnemius - Popliteus - Plantaris (negligible) - of toes Posterior compartment of leg Flexor hallucis longus Flexor digitorum longus Flexor digitorum brevis Quadratus plantae Flexor hallucis brevis Flexor digiti minimi brevis - Posterior compartment of leg Flexor hallucis longus Flexor digitorum longus - Flexor hallucis longus - Flexor digitorum longus - Flexor digitorum brevis - Quadratus plantae - Flexor hallucis brevis - Flexor digiti minimi brevis - of proximal phalanges at metatarsophalangeal joint[10] Lumbrical muscle (foot) Plantar interossei Dorsal interossei - Lumbrical muscle (foot) - Plantar interossei - Dorsal interossei ## Other - torso/lumbar vertebrae Rectus abdominis muscle - Rectus abdominis muscle - neck at atlanto-occipital joint Longus capitis muscle - Longus capitis muscle	https://www.wikidoc.org/index.php/Flexes
0b094ba7fab59b6eccd339e7808ae7a5dda325c8	wikidoc	Floater	Floater # Overview Floaters are deposits of various size, shape, consistency, refractive index, and motility within the eye's normally transparent vitreous humour. They may be of embryonic origin or acquired due to degenerative changes of the vitreous humour or retina. The perception of floaters is known as myodesopsia, or less commonly as myiodeopsia, myiodesopsia, or myodeopsia. When observed subjectively, floaters are entoptic phenomena characterized by shadow-like shapes that appear singly or together with several others in one's field of vision. They may appear as spots, threads, or fragments of cobwebs, which float slowly before one's eyes. Latin-derived Muscae volitantes (meaning 'flying flies'), or French-derived mouches volantes, are a specific type of floater consisting of small spots whose presence is normal and attributed to minute remnants of embryonic structures in the vitreous humour. # Description Floaters are suspended in the vitreous humour, the thick fluid or gel that fills the eye. Thus, they generally follow the rapid motions of the eye, while drifting slowly within the fluid. When they are first noticed, the natural reaction is to attempt to look directly at them. However, attempting to shift one's gaze toward them can be difficult since floaters follow the motion of the eye, remaining to the side of the direction of gaze. Floaters are, in fact, visible only because they do not remain perfectly fixed within the eye. Although the blood vessels of the eye also obstruct light, they are invisible under normal circumstances because they are fixed in location relative to the retina, and the brain "tunes out" stabilized images due to neural adaptation. This does not occur with floaters and they remain visible. Floaters are particularly noticeable when looking at a blank surface or an open monochromal space, such as blue sky. Despite the name "floaters", many of these specks have a tendency to sink toward the bottom of the eyeball, in whichever way the eyeball is oriented; the supine position (looking up or lying back) tends to concentrate them near the fovea, which is the center of gaze, while the textureless and evenly lit sky forms an ideal background against which to view them. Floaters are not uncommon, and do not cause problems for most people; they represent one of the most common presentations to hospital eye services. A survey of optometrists in 2002 suggested that an average of 14 patients per month per optometrist presented with symptoms of floaters in the UK alone. However, floaters are more than a nuisance and a distraction to those with severe cases, especially if the spots seem to constantly drift through the field of vision. The shapes are shadows projected onto the retina by tiny structures of protein or other cell debris discarded over the years and trapped in the vitreous humour. Floaters can even be seen when the eyes are closed on especially bright days, when sufficient light penetrates the eyelids to cast the shadows. It is not, however, only elderly people who suffer from floaters; they can certainly become a problem to younger people, especially if they are myopic. They are also common after cataract operations or after trauma. In some cases, floaters are congenital. Floaters have been known to catch and refract light in ways that somewhat blur vision temporarily until the floater moves to a different area. Many times they trick the sufferer into thinking they see something out of the corner of their eye that really is not there. Most sufferers are able to, with time, learn to ignore their floaters. For people with severe floaters it is nearly impossible to completely ignore the large masses that constantly stay within almost direct view. Some sufferers have noted a decrease in ability to concentrate while reading, watching television, walking outdoors, and driving, especially when tired. # Causes There are various causes for the appearance of floaters, of which the most common are described here. Basically, any way by which material enters the vitreous humour is a cause for floaters. ## Vitreous syneresis The most common cause of floaters is shrinkage of the vitreous humour: this gel-like substance consists of 99% water and 1% solid elements. The solid portion consists of a network of collagen and hyaluronic acid, with the latter retaining water molecules. Depolymerization of this network makes the hyaluronic acid release its trapped water, thereby liquefying the gel. The collagen breaks down into fibrils, which ultimately are the floaters that plague the patient. Floaters caused in this way tend to be few in number and of a linear form. ## Posterior vitreous detachments and retinal detachments In time, the liquefied vitreous body loses support and its framework contracts. This leads to posterior vitreous detachment, in which the vitreous body is released from the sensory retina. During this detachment, the shrinking vitreous can stimulate the retina mechanically, causing the patient to see random flashes across the visual field, sometimes referred to as "flashers." The ultimate release of the vitreous sometimes makes a large floater appear, usually in the shape of a ring ("Weiss ring"). As a complication, part of the retina might be torn off by the departing vitreous body, in a process known as retinal detachment. This will often leak blood into the vitreous, which is seen by the patient as a sudden appearance of numerous small dots, moving across the whole field of vision. Retinal detachment requires immediate medical attention, as it can easily cause blindness. Both the appearance of flashes and the sudden onset of numerous small floaters warrant an ophthalmological investigation. ## Regression of the hyaloid artery The hyaloid artery, an artery running through the vitreous humour during the fetal stage of development, regresses in the third trimester of pregnancy. Its disintegration can sometimes leave cell matter. ## Other common causes Patients with retinal tears may experience floaters if red blood cells are released from leaky blood vessels, and those with a posterior uveitis or vitritis, as in toxoplasmosis, may experience multiple floaters and decreased vision due to the accummulation of white blood cells in the vitreous humour . Other causes for floaters include cystoid macular edema and asteroid hyalosis. The latter is an anomaly of the vitreous humour, where by calcium clumps attach themselves to the collagen network. The bodies that are formed in this way move slightly with eye movement, but then return to their fixed position. ## Tear film debris Sometimes the appearance of floaters has to be attributed to dark specks in the tear film of the eye. Technically, these are not floaters, but they do look the same from the viewpoint of the patient. People with blepharitis or a dysfunctional meibomian gland are especially prone to this cause, but ocular allergies or even the wearing of contact lenses can cause the problem. To differentiate between material in the vitreous humour of the eye and debris in the tear film, one can look at the effect of blinking: debris in the tear film will move quickly with a blink, while floaters are largely unresponsive to it. Tear film debris is diagnosed by eliminating the possibility of true floaters and macular degeneration. # Diagnosis Floaters are often readily observed by a doctor with the use of an ophthalmoscope or slit lamp. However, if the floater is a small piece of debris and near the retina they may not be able to observe it even if it appears large to the sufferer. Increasing background illumination or using a pinhole to effectively decrease pupil diameter may allow a person to obtain a better view of his or her own floaters. The head may be tilted in such a way that one of the floaters drifts towards the central axis of the eye. In the sharpened image the fibrous elements are more conspicuous. (If the pinhole is kept moving slowly in small circles, the same technique evokes an interesting entoptic effect known as the vascular figure, which is a view of the blood vessels within one's own eye.) # Treatment Normally, there is no treatment indicated. Vitrectomy may be successful in treating more severe cases; however, the procedure is typically not warranted in those with lesser symptoms due to the potential for complications as severe as blindness. Floaters may become less annoying as sufferers grow accustomed to them, even to the extent that they may no longer notice them. Another treatment is laser vitreolysis. In this procedure a YAG laser is focused onto the floater and in a quick burst vaporizes the structure into, presumably, a less dense and not as noticeable consistency. This procedure can be time-consuming and there is no consensus as to how completely effective it is. One study found laser vitreolysis "to be a safe but only moderately effective primary treatment conferring clinical benefit in one third of patients".	Floater Template:DiseaseDisorder infobox For patient information click here Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] # Overview Floaters are deposits of various size, shape, consistency, refractive index, and motility within the eye's normally transparent vitreous humour.[1] They may be of embryonic origin or acquired due to degenerative changes of the vitreous humour or retina.[1] The perception of floaters is known as myodesopsia, or less commonly as myiodeopsia, myiodesopsia, or myodeopsia.[1] When observed subjectively, floaters are entoptic phenomena characterized by shadow-like shapes that appear singly or together with several others in one's field of vision. They may appear as spots, threads, or fragments of cobwebs, which float slowly before one's eyes. Latin-derived Muscae volitantes (meaning 'flying flies'), or French-derived mouches volantes, are a specific type of floater consisting of small spots whose presence is normal and attributed to minute remnants of embryonic structures in the vitreous humour.[1] # Description Floaters are suspended in the vitreous humour, the thick fluid or gel that fills the eye. Thus, they generally follow the rapid motions of the eye, while drifting slowly within the fluid. When they are first noticed, the natural reaction is to attempt to look directly at them. However, attempting to shift one's gaze toward them can be difficult since floaters follow the motion of the eye, remaining to the side of the direction of gaze. Floaters are, in fact, visible only because they do not remain perfectly fixed within the eye. Although the blood vessels of the eye also obstruct light, they are invisible under normal circumstances because they are fixed in location relative to the retina, and the brain "tunes out" stabilized images due to neural adaptation. This does not occur with floaters and they remain visible. Floaters are particularly noticeable when looking at a blank surface or an open monochromal space, such as blue sky. Despite the name "floaters", many of these specks have a tendency to sink toward the bottom of the eyeball, in whichever way the eyeball is oriented; the supine position (looking up or lying back) tends to concentrate them near the fovea, which is the center of gaze, while the textureless and evenly lit sky forms an ideal background against which to view them. Floaters are not uncommon, and do not cause problems for most people; they represent one of the most common presentations to hospital eye services. A survey of optometrists in 2002 suggested that an average of 14 patients per month per optometrist presented with symptoms of floaters in the UK alone. However, floaters are more than a nuisance and a distraction to those with severe cases, especially if the spots seem to constantly drift through the field of vision. The shapes are shadows projected onto the retina by tiny structures of protein or other cell debris discarded over the years and trapped in the vitreous humour. Floaters can even be seen when the eyes are closed on especially bright days, when sufficient light penetrates the eyelids to cast the shadows. It is not, however, only elderly people who suffer from floaters; they can certainly become a problem to younger people, especially if they are myopic. They are also common after cataract operations or after trauma. In some cases, floaters are congenital. Floaters have been known to catch and refract light in ways that somewhat blur vision temporarily until the floater moves to a different area. Many times they trick the sufferer into thinking they see something out of the corner of their eye that really is not there. Most sufferers are able to, with time, learn to ignore their floaters. For people with severe floaters it is nearly impossible to completely ignore the large masses that constantly stay within almost direct view. Some sufferers have noted a decrease in ability to concentrate while reading, watching television, walking outdoors, and driving, especially when tired. # Causes There are various causes for the appearance of floaters, of which the most common are described here. Basically, any way by which material enters the vitreous humour is a cause for floaters. ## Vitreous syneresis The most common cause of floaters is shrinkage of the vitreous humour: this gel-like substance consists of 99% water and 1% solid elements. The solid portion consists of a network of collagen and hyaluronic acid, with the latter retaining water molecules. Depolymerization of this network makes the hyaluronic acid release its trapped water, thereby liquefying the gel. The collagen breaks down into fibrils, which ultimately are the floaters that plague the patient. Floaters caused in this way tend to be few in number and of a linear form. ## Posterior vitreous detachments and retinal detachments In time, the liquefied vitreous body loses support and its framework contracts. This leads to posterior vitreous detachment, in which the vitreous body is released from the sensory retina. During this detachment, the shrinking vitreous can stimulate the retina mechanically, causing the patient to see random flashes across the visual field, sometimes referred to as "flashers." The ultimate release of the vitreous sometimes makes a large floater appear, usually in the shape of a ring ("Weiss ring"). As a complication, part of the retina might be torn off by the departing vitreous body, in a process known as retinal detachment. This will often leak blood into the vitreous, which is seen by the patient as a sudden appearance of numerous small dots, moving across the whole field of vision. Retinal detachment requires immediate medical attention, as it can easily cause blindness. Both the appearance of flashes and the sudden onset of numerous small floaters warrant an ophthalmological investigation. ## Regression of the hyaloid artery The hyaloid artery, an artery running through the vitreous humour during the fetal stage of development, regresses in the third trimester of pregnancy. Its disintegration can sometimes leave cell matter. ## Other common causes Patients with retinal tears may experience floaters if red blood cells are released from leaky blood vessels, and those with a posterior uveitis or vitritis, as in toxoplasmosis, may experience multiple floaters and decreased vision due to the accummulation of white blood cells in the vitreous humour [2]. Other causes for floaters include cystoid macular edema and asteroid hyalosis. The latter is an anomaly of the vitreous humour, where by calcium clumps attach themselves to the collagen network. The bodies that are formed in this way move slightly with eye movement, but then return to their fixed position. ## Tear film debris Sometimes the appearance of floaters has to be attributed to dark specks in the tear film of the eye. Technically, these are not floaters, but they do look the same from the viewpoint of the patient. People with blepharitis or a dysfunctional meibomian gland are especially prone to this cause, but ocular allergies or even the wearing of contact lenses can cause the problem. To differentiate between material in the vitreous humour of the eye and debris in the tear film, one can look at the effect of blinking: debris in the tear film will move quickly with a blink, while floaters are largely unresponsive to it. Tear film debris is diagnosed by eliminating the possibility of true floaters and macular degeneration. # Diagnosis Floaters are often readily observed by a doctor with the use of an ophthalmoscope or slit lamp. However, if the floater is a small piece of debris and near the retina they may not be able to observe it even if it appears large to the sufferer. Increasing background illumination or using a pinhole to effectively decrease pupil diameter may allow a person to obtain a better view of his or her own floaters. The head may be tilted in such a way that one of the floaters drifts towards the central axis of the eye. In the sharpened image the fibrous elements are more conspicuous. (If the pinhole is kept moving slowly in small circles, the same technique evokes an interesting entoptic effect known as the vascular figure, which is a view of the blood vessels within one's own eye.) # Treatment Normally, there is no treatment indicated. Vitrectomy may be successful in treating more severe cases;[2] however, the procedure is typically not warranted in those with lesser symptoms due to the potential for complications as severe as blindness. Floaters may become less annoying as sufferers grow accustomed to them, even to the extent that they may no longer notice them. Another treatment is laser vitreolysis. In this procedure a YAG laser is focused onto the floater and in a quick burst vaporizes the structure into, presumably, a less dense and not as noticeable consistency. This procedure can be time-consuming and there is no consensus as to how completely effective it is. One study found laser vitreolysis "to be a safe but only moderately effective primary treatment conferring clinical benefit in one third of patients".[3]	https://www.wikidoc.org/index.php/Floater
c8ea374377f48542f25aa0c7c7f552e6ef6331e1	wikidoc	Fluence	Fluence # Overview In physics, fluence is defined as the number of particles that intersect a unit area . Its units are m-2. In particular, it is used to describe the strength of a radiation field. It is considered one of the fundamental units in dosimetry. It has two equivalent definitions: 1) Imagine that an infinitesimal sphere of cross sectional area da is impinged upon by dN particles of a certain type. Then, the fluence is: \Phi = \frac{{\rm d} N}{{\rm d} a}. 2) Using the same image of a small sphere as above: \Phi = \frac{\sum {\rm d \ell} }{{\rm d} V}, where {\rm d} V is the infintesimal volume and \sum {\rm d \ell} is the sum of all the path lengths of the particles that transverse the volume.	Fluence # Overview In physics, fluence is defined as the number of particles that intersect a unit area . Its units are m-2. In particular, it is used to describe the strength of a radiation field. It is considered one of the fundamental units in dosimetry. It has two equivalent definitions: 1) Imagine that an infinitesimal sphere of cross sectional area da is impinged upon by dN particles of a certain type. Then, the fluence is: <math>\Phi = \frac{{\rm d} N}{{\rm d} a}</math>. 2) Using the same image of a small sphere as above: <math>\Phi = \frac{\sum {\rm d \ell} }{{\rm d} V}</math>, where <math>{\rm d} V </math> is the infintesimal volume and <math>\sum {\rm d \ell}</math> is the sum of all the path lengths of the particles that transverse the volume.	https://www.wikidoc.org/index.php/Fluence
c44ff53c2e18a2ca490d4ce3b6ed6c9c1ea53bd1	wikidoc	Fluency	Fluency # Overview Fluency (also called volubility and loquaciousness) is the property of a person or of a system that delivers information quickly and with expertise. Fluency indicates a very good information processing speed, i.e. very low average time between successively generated messages. # Speech and Language Pathology Fluency is a speech and language pathology term that means the smoothness or flow with which sounds, syllables, words and phrases are joined together when speaking. . Fluency disorders is used as a collective term for cluttering and stuttering. Both disorders have breaks in the fluidity of speech, and both have the fluency breakdown of repetition of parts of speech. Fluency disorders are most often complex in nature and they tend to occur more often in boys than in girls. # Language fluency Language fluency is proficiency in a language, most typically foreign language or another learned language. In this sense, "fluency" actually encompasses a number of related but separable skills: - Reading: the ability to easily read and understand texts written in the language; - Writing: the ability to formulate written texts in the language; - Comprehension: the ability to follow and understand speech in the language; - Speaking: the ability to speak in the language and be understood by its speakers. To some extent, these skills can be separately acquired. Generally, the later in life a learner approaches the study of a foreign language, the harder it is to acquire auditory comprehension and fluent speaking skills. Reading and writing a foreign language are skills that can be acquired more easily after the primary language acquisition period of youth is over, however. # Reading fluency Reading fluency is often confused with fluency with a language (see above). Reading fluency is the ability to read text accurately and quickly. Fluency bridges word decoding and comprehension. Comprehension is understanding what has been read. Fluency is a set of skills that allows readers to rapidly decode text while maintaining high comprehension (National Reading Panel, 2001). A first benchmark for fluency is being able to "sight read" some words. The idea is that children will recognize at sight the most common words in the written form of their native language and that instant reading of these words will allow them to read and understand text more quickly. As children learn to read, the speed at which they read becomes an important measure. (National Reading Panel, Teaching Children to Read: An Evidence-Based Assessment of the Scientific Research Literature on Reading and Its Implications for Reading Instruction--Reports of the Subgroups. A complete copy of the NRP report can be read, downloaded, or ordered at no cost from the NRP website at www.nationalreadingpanel.org.)	Fluency # Overview Fluency (also called volubility and loquaciousness) is the property of a person or of a system that delivers information quickly and with expertise. Fluency indicates a very good information processing speed, i.e. very low average time between successively generated messages. # Speech and Language Pathology Fluency is a speech and language pathology term that means the smoothness or flow with which sounds, syllables, words and phrases are joined together when speaking. [1]. Fluency disorders is used as a collective term for cluttering and stuttering. Both disorders have breaks in the fluidity of speech, and both have the fluency breakdown of repetition of parts of speech. Fluency disorders are most often complex in nature and they tend to occur more often in boys than in girls[2]. # Language fluency Language fluency is proficiency in a language, most typically foreign language or another learned language. In this sense, "fluency" actually encompasses a number of related but separable skills: - Reading: the ability to easily read and understand texts written in the language; - Writing: the ability to formulate written texts in the language; - Comprehension: the ability to follow and understand speech in the language; - Speaking: the ability to speak in the language and be understood by its speakers. To some extent, these skills can be separately acquired. Generally, the later in life a learner approaches the study of a foreign language, the harder it is to acquire auditory comprehension and fluent speaking skills. Reading and writing a foreign language are skills that can be acquired more easily after the primary language acquisition period of youth is over, however. # Reading fluency Reading fluency is often confused with fluency with a language (see above). Reading fluency is the ability to read text accurately and quickly. Fluency bridges word decoding and comprehension. Comprehension is understanding what has been read. Fluency is a set of skills that allows readers to rapidly decode text while maintaining high comprehension (National Reading Panel, 2001). A first benchmark for fluency is being able to "sight read" some words. The idea is that children will recognize at sight the most common words in the written form of their native language and that instant reading of these words will allow them to read and understand text more quickly. As children learn to read, the speed at which they read becomes an important measure. (National Reading Panel, Teaching Children to Read: An Evidence-Based Assessment of the Scientific Research Literature on Reading and Its Implications for Reading Instruction--Reports of the Subgroups. A complete copy of the NRP report can be read, downloaded, or ordered at no cost from the NRP website at www.nationalreadingpanel.org.)	https://www.wikidoc.org/index.php/Fluency
c17f7eb2e8d21dbc437e82f67e0a7d916f510e02	wikidoc	Halogen	Halogen The halogens or halogen elements are a series of nonmetal elements from Group 17 (old-style: VII or VIIA; Group 7 IUPAC Style) of the periodic table, comprising fluorine, F; chlorine, Cl; bromine, Br; iodine, I; and astatine, At. The undiscovered element 117, temporarily named ununseptium, may also be considered a halogen. The group of halogens is the only group which contains elements in all three familiar states of matter at standard temperature and pressure. # Abundance Owing to their high reactivity, the halogens are found in the environment only in compounds or as ions. Halide ions and oxoanions such as IO3− can be found in many minerals and in seawater. Halogenated organic compounds can also be found as natural products in living organisms. In their elemental forms, the halogens exist as diatomic molecules, but these only have a fleeting existence in nature and are much more common in the laboratory and in industry. At room temperature and pressure, fluorine and chlorine are gases, bromine is a liquid and iodine and astatine are solids; Group 17 is therefore the only periodic table group exhibiting all three states of matter at room temperature. # Etymology The term halogen originates from 18th century scientific French nomenclature based on adaptations of Greek roots: hals (sea) or halas (salt), and gen- (to generate) — referring to elements which produce a salt in union with a metal. # Properties The halogens show a number of trends when moving down the group - for instance, decreasing electronegativity and reactivity, increasing melting and boiling point. - Ununseptium has not yet been discovered; values are either unknown if no value appears, or are estimates based on other similar chemicals. # Diatomic halogen molecules # Chemistry ## Reactivity Halogens are highly reactive, and as such can be harmful or lethal to biological organisms in sufficient quantities. This high reactivity is due to their atoms being one electron short of a full outer shell of eight electrons. They can gain this electron by reacting with atoms of other elements. Fluorine is the most reactive element in existence, attacking such inert materials as glass, and forming compounds with the heavier noble gases. It is a corrosive and highly toxic gas. The reactivity of fluorine is such that, if used or stored in laboratory glassware, it can react with glass in the presence of small amounts of water to form SiF4. Thus fluorine must be handled with substances such as Teflon, extremely dry glass, or metals such as copper or steel which form a protective layer of fluoride on their surface. Both chlorine and bromine are used as disinfectants for drinking water, swimming pools, fresh wounds, dishes, and surfaces. They kill bacteria and other potentially harmful microorganisms through a process known as sterilization. Their reactivity is also put to use in bleaching. Sodium hypochlorite, which is produced from chlorine, is the active ingredient of most fabric bleaches and chlorine-derived bleaches are used in the production of some paper products. ## Hydrogen halides The halogens all form binary compounds with hydrogen, the hydrogen halides, HX (HF, HCl, HBr, HI), a series of particularly strong acids. When in aqueous solution, the hydrogen halides are known as hydrohalic acids. HAt, or "hydrastatic acid", should also qualify, but it is not typically included in discussions of hydrohalic acid due to astatine's extreme instability toward alpha decay. ## Interhalogen compounds The halogens react with each other to form interhalogen compounds. Diatomic interhalogen compounds (e.g. BrF, ICl, ClF) bear resemblance to the pure halogens in some respects. The properties and behaviour of a diatomic interhalogen compound tend to be intermediate between those of its parent halogens. Some properties, however, are found in neither parent halogen − Cl2 and I2 are soluble in CCl4 but ICl is not, since it is a polar molecule due to the relatively large electronegativity difference between I and Cl. # Organohalogen compounds Many synthetic organic compounds such as plastic polymers, and a few natural ones, contain halogen atoms; these are known as halogenated compounds or organic halides. Chlorine is by far the most abundant of the halogens, and the only one needed in relatively large amounts (as chloride ions) by humans. For example, chloride ions play a key role in brain function by mediating the action of the inhibitory transmitter GABA and are also used by the body to produce stomach acid. Iodine is needed in trace amounts for the production of thyroid hormones such as thyroxine. On the other hand, neither fluorine nor bromine are believed to be essential for humans, although small amounts of fluoride can make tooth enamel resistant to decay. # Drug discovery In drug discovery, the incorporation of halogen atoms into a lead drug candidate results in analogues that are more lipophilic and less water soluble. Consequently, halogen atoms are used to improve penetration through lipid membranes. However, there is an undesirable tendency for halogenated drugs to accumulate in lipid tissue. The chemical reactivity of halogen atoms depends on both their point of attachment to the lead and the nature of the halogen. Aromatic halogen groups are far less reactive than aliphatic halogen groups, which can exhibit considerable chemical reactivity. For aliphatic carbon-halogen bonds the C-F bond is the strongest and usually less chemically reactive than aliphatic C-H bonds. The other aliphatic-halogen bonds are weaker, their reactivity increasing down the periodic table. They are usually more chemically reactive than aliphatic C-H bonds. Consequently, the most popular halogen substitutions are the less reactive aromatic fluorine and chlorine groups.	Halogen Template:Otheruses1 The halogens or halogen elements are a series of nonmetal elements from Group 17 (old-style: VII or VIIA; Group 7 IUPAC Style) of the periodic table, comprising fluorine, F; chlorine, Cl; bromine, Br; iodine, I; and astatine, At. The undiscovered element 117, temporarily named ununseptium, may also be considered a halogen. The group of halogens is the only group which contains elements in all three familiar states of matter at standard temperature and pressure. # Abundance Owing to their high reactivity, the halogens are found in the environment only in compounds or as ions. Halide ions and oxoanions such as IO3− can be found in many minerals and in seawater. Halogenated organic compounds can also be found as natural products in living organisms. In their elemental forms, the halogens exist as diatomic molecules, but these only have a fleeting existence in nature and are much more common in the laboratory and in industry. At room temperature and pressure, fluorine and chlorine are gases, bromine is a liquid and iodine and astatine are solids; Group 17 is therefore the only periodic table group exhibiting all three states of matter at room temperature. # Etymology The term halogen originates from 18th century scientific French nomenclature based on adaptations of Greek roots: hals (sea) or halas (salt), and gen- (to generate) — referring to elements which produce a salt in union with a metal. # Properties The halogens show a number of trends when moving down the group - for instance, decreasing electronegativity and reactivity, increasing melting and boiling point. * Ununseptium has not yet been discovered; values are either unknown if no value appears, or are estimates based on other similar chemicals. # Diatomic halogen molecules # Chemistry ## Reactivity Halogens are highly reactive, and as such can be harmful or lethal to biological organisms in sufficient quantities. This high reactivity is due to their atoms being one electron short of a full outer shell of eight electrons. They can gain this electron by reacting with atoms of other elements. Fluorine is the most reactive element in existence, attacking such inert materials as glass, and forming compounds with the heavier noble gases. It is a corrosive and highly toxic gas. The reactivity of fluorine is such that, if used or stored in laboratory glassware, it can react with glass in the presence of small amounts of water to form SiF4. Thus fluorine must be handled with substances such as Teflon, extremely dry glass, or metals such as copper or steel which form a protective layer of fluoride on their surface. Both chlorine and bromine are used as disinfectants for drinking water, swimming pools, fresh wounds, dishes, and surfaces. They kill bacteria and other potentially harmful microorganisms through a process known as sterilization. Their reactivity is also put to use in bleaching. Sodium hypochlorite, which is produced from chlorine, is the active ingredient of most fabric bleaches and chlorine-derived bleaches are used in the production of some paper products. ## Hydrogen halides The halogens all form binary compounds with hydrogen, the hydrogen halides, HX (HF, HCl, HBr, HI), a series of particularly strong acids. When in aqueous solution, the hydrogen halides are known as hydrohalic acids. HAt, or "hydrastatic acid", should also qualify, but it is not typically included in discussions of hydrohalic acid due to astatine's extreme instability toward alpha decay. ## Interhalogen compounds The halogens react with each other to form interhalogen compounds. Diatomic interhalogen compounds (e.g. BrF, ICl, ClF) bear resemblance to the pure halogens in some respects. The properties and behaviour of a diatomic interhalogen compound tend to be intermediate between those of its parent halogens. Some properties, however, are found in neither parent halogen − Cl2 and I2 are soluble in CCl4 but ICl is not, since it is a polar molecule due to the relatively large electronegativity difference between I and Cl. # Organohalogen compounds Many synthetic organic compounds such as plastic polymers, and a few natural ones, contain halogen atoms; these are known as halogenated compounds or organic halides. Chlorine is by far the most abundant of the halogens, and the only one needed in relatively large amounts (as chloride ions) by humans. For example, chloride ions play a key role in brain function by mediating the action of the inhibitory transmitter GABA and are also used by the body to produce stomach acid. Iodine is needed in trace amounts for the production of thyroid hormones such as thyroxine. On the other hand, neither fluorine nor bromine are believed to be essential for humans, although small amounts of fluoride can make tooth enamel resistant to decay. # Drug discovery In drug discovery, the incorporation of halogen atoms into a lead drug candidate results in analogues that are more lipophilic and less water soluble. Consequently, halogen atoms are used to improve penetration through lipid membranes. However, there is an undesirable tendency for halogenated drugs to accumulate in lipid tissue. The chemical reactivity of halogen atoms depends on both their point of attachment to the lead and the nature of the halogen. Aromatic halogen groups are far less reactive than aliphatic halogen groups, which can exhibit considerable chemical reactivity. For aliphatic carbon-halogen bonds the C-F bond is the strongest and usually less chemically reactive than aliphatic C-H bonds. The other aliphatic-halogen bonds are weaker, their reactivity increasing down the periodic table. They are usually more chemically reactive than aliphatic C-H bonds. Consequently, the most popular halogen substitutions are the less reactive aromatic fluorine and chlorine groups.	https://www.wikidoc.org/index.php/Fluorine_family
65fc18ba30b2db1c3fe86128924b68f7b4f5082a	wikidoc	Flybase	Flybase FlyBase is an online bioinformatics database of the biology and genome of the model organism Drosophila melanogaster and related Drosophilid dipterans. The FlyBase project is carried out by a consortium of Drosophila researchers and computer scientists at Harvard University and Indiana University in the United States, and University of Cambridge in the United Kingdom. FlyBase is one of the organizations contributing to the Generic Model Organism Database (GMOD). # Contents FlyBase contains a complete rundown of current discoveries in the Drosophila genome. It also includes a searchable bibliography of research on Drosophila genetics in the last century. Information on current researchers, and a partial pedigree of relationships between current researchers, is searchable, based on registration of the participating scientist. The site also provides a large database of images illustrating the full genome, and several movies detailing embryogenesis.	Flybase FlyBase is an online bioinformatics database of the biology and genome of the model organism Drosophila melanogaster and related Drosophilid dipterans. The FlyBase project is carried out by a consortium of Drosophila researchers and computer scientists at Harvard University and Indiana University in the United States, and University of Cambridge in the United Kingdom. FlyBase is one of the organizations contributing to the Generic Model Organism Database (GMOD). # Contents FlyBase contains a complete rundown of current discoveries in the Drosophila genome. It also includes a searchable bibliography of research on Drosophila genetics in the last century. Information on current researchers, and a partial pedigree of relationships between current researchers, is searchable, based on registration of the participating scientist.[1] The site also provides a large database of images illustrating the full genome, and several movies detailing embryogenesis. [2]	https://www.wikidoc.org/index.php/Flybase
a2ab7994f7571c6819c6c3470f0bd5416fe210ab	wikidoc	Forceps	Forceps Forceps are a handheld, hinged instrument used for grasping and holding objects. Forceps are used when fingers are too large to grasp small objects or when many objects need to be held at one time while the hands are used to perform a task. The term forceps is used almost exclusively within the medical field. Outside medicine, people usually refer to forceps as tweezers, tongs, pliers, clips or clamps. The singular and plural form of forceps is always forceps, never 'forcep.' Nor is it referred to as a "pair of" as one refers to a pair of scissors. Grammatically, the word derives from the Latin 'Forca,' meaning a snare or trap. Mechanically, forceps employ the principle of the lever to grasp and apply pressure. Surgical forceps are commonly made of high-grade carbon steel. Lower quality steel is used in forceps made for other uses. High carbon steel ensure that the instruments can withstand repeated sterilization in high-temperature autoclaves. Some forceps, intended to be used once and then discarded, are made of plastic. There are two basic types of forceps: non-locking (often called 'thumb forceps' or 'Pick-ups') and locking, though these two types come in dozens of specialized forms for various uses. Non-locking forceps also come in two basic forms, hinged at one end, away from the grasping end (colloquially such forceps are called tweezers, though a medical professional would not likely refer to them a such) and hinged in the middle, rather like scissors (though, unlike scissors, forceps meet on flat, grasping surfaces rather than in interposing blades). Locking forceps are almost always hinged in the middle, though some forms place the hinge very close to the grasping end. Locking forceps use various means to lock the grasping surfaces in a closed position to facilitate manipulation or to independently clamp, grasp or hold an object. # Thumb forceps Thumb forceps are commonly held between the thumb and two or three fingers of one hand, with the top end resting on the anatomical snuff box at the base of the thumb and index finger. Spring tension at one end holds the grasping ends apart until pressure is applied. This allows one to quickly and easily grasp small objects or tissue to move and release it or to grasp and hold tissue with easily variable pressure. Thumb forceps are used to hold tissue in place when applying sutures, to gently move tissues out of the way during exploratory surgery and to move dressings or draping without using the hands or fingers. Thumb forceps can have smooth tips, cross-hatched tips or serrated tips (often called 'mouse's teeth'). Common arrangements of teeth are 1x2 (two teeth on one side meshing with a single tooth on the other), 7x7 and 9x9. Serrated forceps are used on tissue; counter-intuitively, teeth will damage tissue less than a smooth surface (you can grasp with less overall pressure). Smooth or cross-hatched forceps are used to move dressings, remove sutures and similar tasks. ## Adson tissue forceps Note the 1x2 "mouse's teeth" on the lower tip. File:Adson forceps.jpg # Locking forceps Locking forceps, sometimes called clamps, are used to grasp and hold objects or tissue. When they are used to compress an artery to forestall bleeding they are called hemostats. Another form of locking forceps is the needle holder, used to guide a suturing needle through tissue. Many locking forceps use finger loops to facilitate handling (see illustration, below, of Kelly Forceps). The finger loops are usually grasped by the thumb and middle or ring fingers, while the index finger helps guide the instrument. The most common locking mechanism is a series of interlocking teeth located near the finger loops. As the forceps are closed, the teeth engage and keep the instrument's grasping surfaces from separating. A simple shift of the fingers is all that is needed to dis-engage the teeth and allow the grasping ends to move apart. Forceps are also used for surgery. ## Kelly Forceps Shown closed and open. Note the toothed locking mechanism near the finger loops. File:Kelly Forceps.jpg # Forceps in childbirth Forceps can be used to assist the delivery of a baby as an alternative to the ventouse method. See forceps in childbirth.	Forceps Forceps are a handheld, hinged instrument used for grasping and holding objects. Forceps are used when fingers are too large to grasp small objects or when many objects need to be held at one time while the hands are used to perform a task. The term forceps is used almost exclusively within the medical field. Outside medicine, people usually refer to forceps as tweezers, tongs, pliers, clips or clamps. The singular and plural form of forceps is always forceps, never 'forcep.' Nor is it referred to as a "pair of" as one refers to a pair of scissors. Grammatically, the word derives from the Latin 'Forca,' meaning a snare or trap. Mechanically, forceps employ the principle of the lever to grasp and apply pressure. Surgical forceps are commonly made of high-grade carbon steel. Lower quality steel is used in forceps made for other uses. High carbon steel ensure that the instruments can withstand repeated sterilization in high-temperature autoclaves. Some forceps, intended to be used once and then discarded, are made of plastic. There are two basic types of forceps: non-locking (often called 'thumb forceps' or 'Pick-ups') and locking, though these two types come in dozens of specialized forms for various uses. Non-locking forceps also come in two basic forms, hinged at one end, away from the grasping end (colloquially such forceps are called tweezers, though a medical professional would not likely refer to them a such) and hinged in the middle, rather like scissors (though, unlike scissors, forceps meet on flat, grasping surfaces rather than in interposing blades). Locking forceps are almost always hinged in the middle, though some forms place the hinge very close to the grasping end. Locking forceps use various means to lock the grasping surfaces in a closed position to facilitate manipulation or to independently clamp, grasp or hold an object. # Thumb forceps Thumb forceps are commonly held between the thumb and two or three fingers of one hand, with the top end resting on the anatomical snuff box at the base of the thumb and index finger. Spring tension at one end holds the grasping ends apart until pressure is applied. This allows one to quickly and easily grasp small objects or tissue to move and release it or to grasp and hold tissue with easily variable pressure. Thumb forceps are used to hold tissue in place when applying sutures, to gently move tissues out of the way during exploratory surgery and to move dressings or draping without using the hands or fingers. Thumb forceps can have smooth tips, cross-hatched tips or serrated tips (often called 'mouse's teeth'). Common arrangements of teeth are 1x2 (two teeth on one side meshing with a single tooth on the other), 7x7 and 9x9. Serrated forceps are used on tissue; counter-intuitively, teeth will damage tissue less than a smooth surface (you can grasp with less overall pressure). Smooth or cross-hatched forceps are used to move dressings, remove sutures and similar tasks. ## Adson tissue forceps Note the 1x2 "mouse's teeth" on the lower tip. File:Adson forceps.jpg # Locking forceps Locking forceps, sometimes called clamps, are used to grasp and hold objects or tissue. When they are used to compress an artery to forestall bleeding they are called hemostats. Another form of locking forceps is the needle holder, used to guide a suturing needle through tissue. Many locking forceps use finger loops to facilitate handling (see illustration, below, of Kelly Forceps). The finger loops are usually grasped by the thumb and middle or ring fingers, while the index finger helps guide the instrument. The most common locking mechanism is a series of interlocking teeth located near the finger loops. As the forceps are closed, the teeth engage and keep the instrument's grasping surfaces from separating. A simple shift of the fingers is all that is needed to dis-engage the teeth and allow the grasping ends to move apart. Forceps are also used for surgery. ## Kelly Forceps Shown closed and open. Note the toothed locking mechanism near the finger loops. File:Kelly Forceps.jpg # Forceps in childbirth Forceps can be used to assist the delivery of a baby as an alternative to the ventouse method. See forceps in childbirth. Template:WikiDoc Sources	https://www.wikidoc.org/index.php/Forceps
c1ba4c46b306ffb0ac171d93ada00ad09411706d	wikidoc	Formins	Formins Formins (formin homology proteins) are a group of proteins that are involved in the polymerization of actin and associate with the fast-growing end (barbed end) of actin filaments. Most formins are Rho-GTPase effector proteins. Formins regulate the actin and microtubule cytoskeleton and are involved in various cellular functions such as cell polarity, cytokinesis, cell migration and SRF transcriptional activity. Formins are multidomain proteins that interact with diverse signalling molecules and cytoskeletal proteins, although some formins have been assigned functions within the nucleus. # Diversity Formins have been found in all eukaryotes studied. In humans, 15 different formin proteins are present that have been classified in 7 subgroups. By contrast, yeasts contain only 2-3 formins. # Structure and interactions Formins are characterized by the presence of three formin homology (FH) domains (FH1, FH2 and FH3), although members of the formin family do not necessarily contain all three domains. In addition, other domains are usually present, such as PDZ, DAD, WH2, or FHA domains. The proline-rich FH1 domain mediates interactions with a variety of proteins, including the actin-binding protein profilin, SH3 (Src homology 3) domain proteins, and WW domain proteins. The actin nucleation-promoting activity of S. cerevisiae formins has been localized to the FH2 domain. The FH2 domain is required for the self-association of formin proteins through the ability of FH2 domains to directly bind each other, and may also act to inhibit actin polymerization. The FH3 domain is less well conserved and is required for directing formins to the correct intracellular location, such the mitotic spindle, or the projection tip during conjugation. In addition, some formins can contain a GTPase-binding domain (GBD) required for binding to Rho small GTPases, and a C-terminal conserved Dia-autoregulatory domain (DAD). The GBD is a bifunctional autoinhibitory domain that interacts with and is regulated by activated Rho family members. Mammalian Drf3 contains a CRIB-like motif within its GBD for binding to Cdc42, which is required for Cdc42 to activate and guide Drf3 towards the cell cortex where it remodels the actin skeleton. The DAD binds the N-terminal GBD; this link is broken when GTP-bound Rho binds to the GBD and activates the protein. The addition of the DAD to mammalian cells induces actin filament formation, stabilizes microtubules, and activates SRF mediated transcription. Another commonly found domain is an armadillo repeat region (ARR) located in the FH3 domain. The FH2 domain, has been shown by X-ray crystallography to have an elongated, crescent shape containing three helical subdomains. Formins also directly bind to microtubules via their FH2 domain. This interaction is important in promoting the capture and stabilization of a subset of microtubules oriented towards the leading edge of migrating cells. Formins also promote the capture of microtubules by the kinetochore during mitosis and for aligning microtubules along actin filaments.	Formins Formins (formin homology proteins) are a group of proteins that are involved in the polymerization of actin and associate with the fast-growing end (barbed end) of actin filaments.[2] Most formins are Rho-GTPase effector proteins. Formins regulate the actin and microtubule cytoskeleton [3][4] and are involved in various cellular functions such as cell polarity, cytokinesis, cell migration and SRF transcriptional activity.[5] Formins are multidomain proteins that interact with diverse signalling molecules and cytoskeletal proteins, although some formins have been assigned functions within the nucleus. # Diversity Formins have been found in all eukaryotes studied.[1] In humans, 15 different formin proteins are present that have been classified in 7 subgroups.[6] By contrast, yeasts contain only 2-3 formins.[7] # Structure and interactions Formins are characterized by the presence of three formin homology (FH) domains (FH1, FH2 and FH3), although members of the formin family do not necessarily contain all three domains.[8][9] In addition, other domains are usually present, such as PDZ, DAD, WH2, or FHA domains. The proline-rich FH1 domain mediates interactions with a variety of proteins, including the actin-binding protein profilin, SH3 (Src homology 3) domain proteins,[10] and WW domain proteins. The actin nucleation-promoting activity of S. cerevisiae formins has been localized to the FH2 domain.[4] The FH2 domain is required for the self-association of formin proteins through the ability of FH2 domains to directly bind each other, and may also act to inhibit actin polymerization.[11][12] The FH3 domain is less well conserved and is required for directing formins to the correct intracellular location, such the mitotic spindle, or the projection tip during conjugation.[13][14] In addition, some formins can contain a GTPase-binding domain (GBD) required for binding to Rho small GTPases, and a C-terminal conserved Dia-autoregulatory domain (DAD). The GBD is a bifunctional autoinhibitory domain that interacts with and is regulated by activated Rho family members. Mammalian Drf3 contains a CRIB-like motif within its GBD for binding to Cdc42, which is required for Cdc42 to activate and guide Drf3 towards the cell cortex where it remodels the actin skeleton.[15] The DAD binds the N-terminal GBD; this link is broken when GTP-bound Rho binds to the GBD and activates the protein. The addition of the DAD to mammalian cells induces actin filament formation, stabilizes microtubules, and activates SRF mediated transcription.[15] Another commonly found domain is an armadillo repeat region (ARR) located in the FH3 domain. The FH2 domain, has been shown by X-ray crystallography to have an elongated, crescent shape containing three helical subdomains.[16][17] Formins also directly bind to microtubules via their FH2 domain. This interaction is important in promoting the capture and stabilization of a subset of microtubules oriented towards the leading edge of migrating cells. Formins also promote the capture of microtubules by the kinetochore during mitosis and for aligning microtubules along actin filaments.[18][19]	https://www.wikidoc.org/index.php/Formins
a9f92bf8429b947101c77f6d06f55131e7a13e27	wikidoc	Fouling	Fouling Fouling refers to the accumulation and deposition of living organisms (biofouling) and certain non-living material on hard surfaces, most often in an aquatic environment. This can be the fouling of ships, pilings, and natural surfaces in the marine environment (marine fouling), fouling of heat-transferring components through ingredients contained in the cooling water or gases, and even the development of plaque on teeth or deposits on solar panels on Mars, among other examples. This article is mostly devoted to the fouling of heat exchanger systems, although many of the points made are applicable to other varieties of fouling. In the cooling technology and other technical fields, a distinction is made between macro fouling and micro fouling. Of the two, micro fouling is the one which is usually more difficult to prevent and therefore more important. # Macro fouling Macro fouling is caused by coarse matter of either biological or inorganic origin, for example industrially produced refuse. Such matter enters into the cooling water circuit through the cooling water pumps from sources like the open sea, rivers or lakes. In closed circuits, like cooling towers, the ingress of macro fouling into the cooling tower basin is possible through open canals or by the wind. Sometimes, parts of the cooling tower internals detach themselves and are carried into the cooling water circuit. Such substances can foul the surfaces of heat exchangers and may cause deterioration of the relevant heat transfer coefficient. They may also create flow blockages, redistribute the flow inside the components, or cause fretting damage. - Manmade refuse - Detached internal parts of components - Algae - Mussels - Leaves, parts of plants up to entire trunks # Micro fouling As to micro fouling, distinctions are made between: - Scaling or precipitation fouling, as crystallization of solid salts, oxides and hydroxides from water solutions, for example Calcium carbonate (aragonite or calcite) Calcium sulfate (anhydrite, hemihydrate, gypsum) Silicates (serpentine, analcite, acmite, gyrolite, noselite, gehlenite, amorphous silica, cristoballite) Magnesium hydroxide (brucite) Aluminum oxide (boehmite, gibbsite, corundum) Copper (metalic copper, cuprite) Barium sulfate - Calcium carbonate (aragonite or calcite) - Calcium sulfate (anhydrite, hemihydrate, gypsum) - Silicates (serpentine, analcite, acmite, gyrolite, noselite, gehlenite, amorphous silica, cristoballite) - Magnesium hydroxide (brucite) - Aluminum oxide (boehmite, gibbsite, corundum) - Copper (metalic copper, cuprite) - Barium sulfate - Particulate fouling, i.e., accumulation of particles, typically colloidal particles, on a surface Iron oxides and oxyhydroxides (magnetite, hematite, lepidocrocite, maghemite, goethite) - Iron oxides and oxyhydroxides (magnetite, hematite, lepidocrocite, maghemite, goethite) - Sedimentation fouling by silt and other relatively coarse suspended matter - Corrosion fouling, i.e., in-situ growth of corrosion deposits, for example magnetite on carbon steel surfaces - Chemical reaction fouling, for example decomposition or polymerization of organic matter on heating surfaces - Biofouling, like settlements of bacteria and algae - Composite fouling, whereby fouling involves more than one foulant or fouling mechanism. ## Precipitation fouling Through changes in temperature, or solvent evaporation or degasification, the concentration of salts may exceed the saturation, leading to a precipitation of salt crystals. Precipitation fouling is a very common problem in boilers and heat exchangers operating with hard water and often results in limescale. As an example, the equilibrium between the readily soluble calcium bicarbonate - always prevailing in natural water - and the poorly soluble calcium carbonate, the following chemical equation may be written: The calcium carbonate that has formed through this reaction precipitates. Due to the temperature dependence of the reaction, the scaling is higher at the hotter outlet of the heat exchanger than at the cooler inlet. In general, the dependence of the salt solubility on temperature or presence of evaporation will often be the driving force for precipitation fouling. The important distinction is between salts with "normal" or "retrograde" dependence of solubility on temperature. The salts with the "normal" solubility decrease their solubility with temperature and thus will foul the cooling sufaces. The salts with "inverse" or "retrograte" solubility will foul the heating surfaces. ## Particulate fouling Fouling by particles suspended in water ("crud") or in gas progresses by a mechanism different than precipitation fouling. This process is usually most important for colloidal particles, i.e., particles smaller than about 1 μm in at least one dimension (but which are much larger than atomic dimensions). Particles are transported to the surface by a number of mechanisms and there they can attach themselves, e.g., by flocculation or coagulation. Note that the attachment of colloidal particles typically involves electrical forces and thus the particle behaviour defies the experience from the macroscopic world. The probability of attachment is sometimes referred to as "sticking probability", which for colloidal particles is a function of both the surface chemistry and the local thermohydraulic conditions. With time, the resulting surface deposit may harden through processes collectively known as "deposit consolidation" or, colloquially, "aging". ## Chemical reaction fouling Chemical reactions may occur on contact of the components of the process fluid with heat transfer surfaces. In such cases, the metallic surface sometimes acts as a catalyst. For example, corrosion and polymerization occurs in cooling water for the chemical industry which has a minor content of hydrocarbons. Systems in petroleum processing are prone to polymerization of olefins or deposition of heavy fractions (asphaltenes, waxes, etc). High tube wall temperatures may lead to carbonizing of organic matter. Food industry, for example milk processing, also experiences fouling problems by chemical reactions. ## Corrosion fouling Corrosion deposits are created in-situ by the corrosion of the substrate. They are distinguished from fouling deposits, which form from material originating ex-situ. Corrosion deposits should not be confused with fouling deposits formed by ex-situ generated corrosion products. Corrosion deposits will normally have composition related to the composition of the substrate. An example of corrosion fouling can be formation of an iron oxide or oxyhydroxide deposit from corrosion of the carbon steel underneath. ## Biofouling Biofouling or biological fouling is the undesirable accumulation of micro-organisms, plants, algae, and animals on structures, for example ships' hulls. Water piping systems carrying untreated water are also often subject of biofouling. ## Composite fouling Composite fouling is common. This type of fouling involves more than one foulant or more than one fouling mechanism working simultaneously. The multiple foulants or mechanisms may interact with each other resulting in a synergistic fouling which is not a simple arithmetic sum of the individual components. ## Fouling on Mars NASA Mars Exploration Rovers (Spirit and Opportunity) experienced fouling of solar panels by dust particles from the Martian atmosphere. Some of the deposits subsequently spontaneously cleaned off. This illustrates the universal nature of the fouling phenomena. # Fouling modelling Fouling of a system can be modelled as consisting of several steps: - Generation or ingress of the species that causes fouling ("foulant sourcing") - Foulant transport with the stream of the process fluid - Foulant transport from the bulk of the process fluid to the fouling surface - Induction period, i.e., a near-nil fouling rate at the initial period of fouling (observed only for some fouling mechanisms) - Foulant crystallization on the surface (or attachment of the colloidal particle, or chemical reaction, or bacterial growth) - Deposit dissolution (or re-entrainment of particles) - Deposit consolidation on the surface - Deposit spalling Deposition consists of transport to the surface and subsequent attachment. Deposit removal is either through deposit dissolution, particle re-entrainment or deposit spalling. Fouling results from foulant generation, foulant deposition, deposit removal, and deposit consolidation. # Quantification of fouling The most straight-forward way to quantify fairly uniform fouling is by stating the average deposit surface loading, i.e., kg of deposit per m² of surface area. The fouling rate will then be expressed in kg/m²s, and it is obtained by dividing the deposit surface loading by the effective operating time. The normalized fouling rate (also in kg/m²s) will additionally account for the concentration of the foulant in the process fluid (kg/kg) during preceding operations, and is useful for comparison of fouling rates between different systems. It is obtained by dividing the fouling rate by the foulant concentration. The fouling rate constant (m/s) can be obtained by dividing the normalized fouling rate by the mass density of the process fluid (kg/m³). Deposit thickness (μm) and porosity (%) are also often used for description of fouling amount. The relative reduction of diameter of piping or increase of the surface roughness can be of particular interest when the impact of fouling on pressure drop is of interest. In heat transfer equipment, where the primary concern is often the effect of fouling on heat transfer, fouling can be quantified by the increase of the resistance to the flow of heat (m²K/W) due to fouling (termed "fouling resistance"), or by development of heat transfer coefficient (W/m²K) with time. If under-deposit or crevice corrosion is of primary concern, it is important to note packing of confined regions with deposits or creation of occluded "crevices". The non-uniformity of deposit thickness (e.g., deposit waviness) can also be important if underdeposit corrosion of material (e.g., intergranular attack, pitting, stress corrosion cracking) is of concern. # The economic importance of fouling Fouling is ubiquitous and generates tremendous operational losses, not unlike corrosion. For example, one estimate puts the losses due to fouling of heat exchangers in industrialized nations to be about 0.25% of their GDP. The losses initially result from impaired heat transfer, corrosion damage (in particular under-deposit and crevice corrosion), increased pressure drop, flow blockages, flow redistribution inside components, flow instabilities, induced vibrations, fretting, premature failure of electrical heating elements, and a large number of other often unanticipated problems. In addition, the ecological costs should be (but typically are not) considered. The ecological costs arise from the use of biocides for the avoidance of biofouling, and from the increased fuel input to compensate for the reduced output caused by fouling. For example, "normal" fouling at a conventionally fired 500 MW (net electrical power) power station unit accounts for output losses of the steam turbine of 5 MW and more. In a 1,300 MW nuclear power station, typical losses could be 20 MW and up (up to 100% if the station shuts down due to fouling-induced component degradation). In seawater desalination plants, fouling may reduce the gained output ratio by two-digit percentages. (The gained output ratio is an equivalent that puts the mass of generated distillate in relation to the steam used in the process.) The extra electrical consumption in compressor-operated coolers is also easily in the two-digit area. In addition to the operational costs, also the capital cost increases because the heat exchangers have to be designed in larger sizes to compensate for the heat-transfer loss due to fouling. To the output losses listed above, one needs to add the cost of down-time required to inspect, clean, and repair the components (millions of dollars per day of shutdown in lost revenue in a typical power plant), and the cost of actually doing this maintenance. Finally, fouling is often a root cause of serious degradation problems that may limit the life of components or entire plants. # Fouling control The most fundamental and usually preferred method of controlling fouling is to prevent the ingress of the fouling species into the cooling water circuit. In steam power stations and other major industrial installations of water technology, macro fouling is avoided by way of pre-filtration and cooling water debris filters. In the case of micro fouling, water purification is achieved with extensive methods of water treatment, membrane technology (reverse osmosis) or ion-exchange resins. The generation of the corrosion products in the water piping systems is often minimized by controlling the pH of the process fluid (typically alkanization with ammonia, morpholine, ethanolamine or sodium phosphate), control of oxygen dissolved in water (for example, by addition of hydrazine), or addition of corrosion inhibitors. For water systems at relatively low temperatures, the applied biocides may be classified as follows: inorganic chlorine and bromide compounds, chlorine and bromide cleavers, ozone and oxygen cleavers, unoxidizable biocides. One of the most important unoxidizable biocides is a mixture of chloromethyl-isothiazolinone and methyl-isothiazolinone. Also applied are dibrom nitrilopropionamide and quaternary ammonium compounds. Chemical fouling inhibitors can reduce fouling in many systems, mainly by interfering with the crystallization, attachement, or consolidation steps of the fouling process. Examples are: chelating agents (for example, EDTA), long-chain aliphatic amines or polyamines (for example, octadecylamine, helamin, and other "film-forming" amines), organic phosphonic acids (for example, 1-hydroxyethylidene-1,1-diphosphonic acid, known as HEDP), or polyelectrolytes (for example, polyacrylic acid, polymethacrylic acid, usually with a molecular weight lower than 10000). On the component design level, fouling can often (but not always) be minimized by maintaining a relatively high (for example, 2 m/s) and uniform fluid velocity throughout the component. Stagnant regions need to be eliminated. Component is normally overdesigned to accommodate the fouling anticipated between cleanings. However, a significant overdesign can be a design error because it may lead to increased fouling due to reduced velocities. Periodic on-line pressure pulses or backflow can be effective if the capability is carefully incorporated at the design time. Blowdown capability is always incorporated into steam generators or evaporators to control the accumulation of non-volatile impurities the cause or aggreviate fouling. Low-fouling surfaces (for example, very smooth, implanted with ions, or of low surface energy like Teflon) are an option for some applications. Modern components are typically required to be designed for ease of inspection of internals and periodic cleaning. Chemical or mechanical cleaning processes for the removal of deposits and scales are recommended when fouling reaches the point of impacting the system performance. These processes comprise pickling with acids and metal complexing agents, cleaning with high-velocity water jets ("water lancing"), or recirculating sponge rubber balls. Whereas chemical cleaning causes environmental problems through the handling, application, storage and disposal of chemicals, the mechanical cleaning by means of circulating cleaning balls can be a more environmentally-friendly alternative. Also ultrasonic or abrasive cleaning methods are available for many specific applications.	Fouling Fouling refers to the accumulation and deposition of living organisms (biofouling) and certain non-living material on hard surfaces, most often in an aquatic environment. This can be the fouling of ships, pilings, and natural surfaces in the marine environment (marine fouling), fouling of heat-transferring components through ingredients contained in the cooling water or gases, and even the development of plaque on teeth or deposits on solar panels on Mars, among other examples. This article is mostly devoted to the fouling of heat exchanger systems, although many of the points made are applicable to other varieties of fouling. In the cooling technology and other technical fields, a distinction is made between macro fouling and micro fouling. Of the two, micro fouling is the one which is usually more difficult to prevent and therefore more important. # Macro fouling Macro fouling is caused by coarse matter of either biological or inorganic origin, for example industrially produced refuse. Such matter enters into the cooling water circuit through the cooling water pumps from sources like the open sea, rivers or lakes. In closed circuits, like cooling towers, the ingress of macro fouling into the cooling tower basin is possible through open canals or by the wind. Sometimes, parts of the cooling tower internals detach themselves and are carried into the cooling water circuit. Such substances can foul the surfaces of heat exchangers and may cause deterioration of the relevant heat transfer coefficient. They may also create flow blockages, redistribute the flow inside the components, or cause fretting damage. - Manmade refuse - Detached internal parts of components - Algae - Mussels - Leaves, parts of plants up to entire trunks # Micro fouling As to micro fouling, distinctions are made between: - Scaling or precipitation fouling, as crystallization of solid salts, oxides and hydroxides from water solutions, for example Calcium carbonate (aragonite or calcite) Calcium sulfate (anhydrite, hemihydrate, gypsum) Silicates (serpentine, analcite, acmite, gyrolite, noselite, gehlenite, amorphous silica, cristoballite) Magnesium hydroxide (brucite) Aluminum oxide (boehmite, gibbsite, corundum) Copper (metalic copper, cuprite) Barium sulfate - Calcium carbonate (aragonite or calcite) - Calcium sulfate (anhydrite, hemihydrate, gypsum) - Silicates (serpentine, analcite, acmite, gyrolite, noselite, gehlenite, amorphous silica, cristoballite) - Magnesium hydroxide (brucite) - Aluminum oxide (boehmite, gibbsite, corundum) - Copper (metalic copper, cuprite) - Barium sulfate - Particulate fouling, i.e., accumulation of particles, typically colloidal particles, on a surface Iron oxides and oxyhydroxides (magnetite, hematite, lepidocrocite, maghemite, goethite) - Iron oxides and oxyhydroxides (magnetite, hematite, lepidocrocite, maghemite, goethite) - Sedimentation fouling by silt and other relatively coarse suspended matter - Corrosion fouling, i.e., in-situ growth of corrosion deposits, for example magnetite on carbon steel surfaces - Chemical reaction fouling, for example decomposition or polymerization of organic matter on heating surfaces - Biofouling, like settlements of bacteria and algae - Composite fouling, whereby fouling involves more than one foulant or fouling mechanism. ## Precipitation fouling Through changes in temperature, or solvent evaporation or degasification, the concentration of salts may exceed the saturation, leading to a precipitation of salt crystals. Precipitation fouling is a very common problem in boilers and heat exchangers operating with hard water and often results in limescale. As an example, the equilibrium between the readily soluble calcium bicarbonate - always prevailing in natural water - and the poorly soluble calcium carbonate, the following chemical equation may be written: The calcium carbonate that has formed through this reaction precipitates. Due to the temperature dependence of the reaction, the scaling is higher at the hotter outlet of the heat exchanger than at the cooler inlet. In general, the dependence of the salt solubility on temperature or presence of evaporation will often be the driving force for precipitation fouling. The important distinction is between salts with "normal" or "retrograde" dependence of solubility on temperature. The salts with the "normal" solubility decrease their solubility with temperature and thus will foul the cooling sufaces. The salts with "inverse" or "retrograte" solubility will foul the heating surfaces. ## Particulate fouling Fouling by particles suspended in water ("crud") or in gas progresses by a mechanism different than precipitation fouling. This process is usually most important for colloidal particles, i.e., particles smaller than about 1 μm in at least one dimension (but which are much larger than atomic dimensions). Particles are transported to the surface by a number of mechanisms and there they can attach themselves, e.g., by flocculation or coagulation. Note that the attachment of colloidal particles typically involves electrical forces and thus the particle behaviour defies the experience from the macroscopic world. The probability of attachment is sometimes referred to as "sticking probability", which for colloidal particles is a function of both the surface chemistry and the local thermohydraulic conditions. With time, the resulting surface deposit may harden through processes collectively known as "deposit consolidation" or, colloquially, "aging". ## Chemical reaction fouling Chemical reactions may occur on contact of the components of the process fluid with heat transfer surfaces. In such cases, the metallic surface sometimes acts as a catalyst. For example, corrosion and polymerization occurs in cooling water for the chemical industry which has a minor content of hydrocarbons. Systems in petroleum processing are prone to polymerization of olefins or deposition of heavy fractions (asphaltenes, waxes, etc). High tube wall temperatures may lead to carbonizing of organic matter. Food industry, for example milk processing, also experiences fouling problems by chemical reactions. ## Corrosion fouling Corrosion deposits are created in-situ by the corrosion of the substrate. They are distinguished from fouling deposits, which form from material originating ex-situ. Corrosion deposits should not be confused with fouling deposits formed by ex-situ generated corrosion products. Corrosion deposits will normally have composition related to the composition of the substrate. An example of corrosion fouling can be formation of an iron oxide or oxyhydroxide deposit from corrosion of the carbon steel underneath. ## Biofouling Biofouling or biological fouling is the undesirable accumulation of micro-organisms, plants, algae, and animals on structures, for example ships' hulls. Water piping systems carrying untreated water are also often subject of biofouling. ## Composite fouling Composite fouling is common. This type of fouling involves more than one foulant or more than one fouling mechanism[1] working simultaneously. The multiple foulants or mechanisms may interact with each other resulting in a synergistic fouling which is not a simple arithmetic sum of the individual components. ## Fouling on Mars NASA Mars Exploration Rovers (Spirit and Opportunity) experienced fouling of solar panels by dust particles from the Martian atmosphere[2]. Some of the deposits subsequently spontaneously cleaned off. This illustrates the universal nature of the fouling phenomena. # Fouling modelling Fouling of a system can be modelled as consisting of several steps: - Generation or ingress of the species that causes fouling ("foulant sourcing") - Foulant transport with the stream of the process fluid - Foulant transport from the bulk of the process fluid to the fouling surface - Induction period, i.e., a near-nil fouling rate at the initial period of fouling (observed only for some fouling mechanisms) - Foulant crystallization on the surface (or attachment of the colloidal particle, or chemical reaction, or bacterial growth) - Deposit dissolution (or re-entrainment of particles) - Deposit consolidation on the surface - Deposit spalling Deposition consists of transport to the surface and subsequent attachment. Deposit removal is either through deposit dissolution, particle re-entrainment or deposit spalling. Fouling results from foulant generation, foulant deposition, deposit removal, and deposit consolidation. # Quantification of fouling The most straight-forward way to quantify fairly uniform fouling is by stating the average deposit surface loading, i.e., kg of deposit per m² of surface area. The fouling rate will then be expressed in kg/m²s, and it is obtained by dividing the deposit surface loading by the effective operating time. The normalized fouling rate (also in kg/m²s) will additionally account for the concentration of the foulant in the process fluid (kg/kg) during preceding operations, and is useful for comparison of fouling rates between different systems. It is obtained by dividing the fouling rate by the foulant concentration. The fouling rate constant (m/s) can be obtained by dividing the normalized fouling rate by the mass density of the process fluid (kg/m³). Deposit thickness (μm) and porosity (%) are also often used for description of fouling amount. The relative reduction of diameter of piping or increase of the surface roughness can be of particular interest when the impact of fouling on pressure drop is of interest. In heat transfer equipment, where the primary concern is often the effect of fouling on heat transfer, fouling can be quantified by the increase of the resistance to the flow of heat (m²K/W) due to fouling (termed "fouling resistance"), or by development of heat transfer coefficient (W/m²K) with time. If under-deposit or crevice corrosion is of primary concern, it is important to note packing of confined regions with deposits or creation of occluded "crevices". The non-uniformity of deposit thickness (e.g., deposit waviness) can also be important if underdeposit corrosion of material (e.g., intergranular attack, pitting, stress corrosion cracking) is of concern. # The economic importance of fouling Fouling is ubiquitous and generates tremendous operational losses, not unlike corrosion. For example, one estimate puts the losses due to fouling of heat exchangers in industrialized nations to be about 0.25% of their GDP[3]. The losses initially result from impaired heat transfer, corrosion damage (in particular under-deposit and crevice corrosion), increased pressure drop, flow blockages, flow redistribution inside components, flow instabilities, induced vibrations, fretting, premature failure of electrical heating elements, and a large number of other often unanticipated problems. In addition, the ecological costs should be (but typically are not) considered. The ecological costs arise from the use of biocides for the avoidance of biofouling, and from the increased fuel input to compensate for the reduced output caused by fouling. For example, "normal" fouling at a conventionally fired 500 MW (net electrical power) power station unit accounts for output losses of the steam turbine of 5 MW and more. In a 1,300 MW nuclear power station, typical losses could be 20 MW and up (up to 100% if the station shuts down due to fouling-induced component degradation). In seawater desalination plants, fouling may reduce the gained output ratio by two-digit percentages. (The gained output ratio is an equivalent that puts the mass of generated distillate in relation to the steam used in the process.) The extra electrical consumption in compressor-operated coolers is also easily in the two-digit area. In addition to the operational costs, also the capital cost increases because the heat exchangers have to be designed in larger sizes to compensate for the heat-transfer loss due to fouling. To the output losses listed above, one needs to add the cost of down-time required to inspect, clean, and repair the components (millions of dollars per day of shutdown in lost revenue in a typical power plant), and the cost of actually doing this maintenance. Finally, fouling is often a root cause of serious degradation problems that may limit the life of components or entire plants. # Fouling control The most fundamental and usually preferred method of controlling fouling is to prevent the ingress of the fouling species into the cooling water circuit. In steam power stations and other major industrial installations of water technology, macro fouling is avoided by way of pre-filtration and cooling water debris filters. In the case of micro fouling, water purification is achieved with extensive methods of water treatment, membrane technology (reverse osmosis) or ion-exchange resins. The generation of the corrosion products in the water piping systems is often minimized by controlling the pH of the process fluid (typically alkanization with ammonia, morpholine, ethanolamine or sodium phosphate), control of oxygen dissolved in water (for example, by addition of hydrazine), or addition of corrosion inhibitors. For water systems at relatively low temperatures, the applied biocides may be classified as follows: inorganic chlorine and bromide compounds, chlorine and bromide cleavers, ozone and oxygen cleavers, unoxidizable biocides. One of the most important unoxidizable biocides is a mixture of chloromethyl-isothiazolinone and methyl-isothiazolinone. Also applied are dibrom nitrilopropionamide and quaternary ammonium compounds. Chemical fouling inhibitors[4] can reduce fouling in many systems, mainly by interfering with the crystallization, attachement, or consolidation steps of the fouling process. Examples are: chelating agents (for example, EDTA), long-chain aliphatic amines or polyamines (for example, octadecylamine, helamin, and other "film-forming" amines), organic phosphonic acids (for example, 1-hydroxyethylidene-1,1-diphosphonic acid, known as HEDP), or polyelectrolytes (for example, polyacrylic acid, polymethacrylic acid, usually with a molecular weight lower than 10000). On the component design level, fouling can often (but not always) be minimized by maintaining a relatively high (for example, 2 m/s) and uniform fluid velocity throughout the component. Stagnant regions need to be eliminated. Component is normally overdesigned to accommodate the fouling anticipated between cleanings. However, a significant overdesign can be a design error because it may lead to increased fouling due to reduced velocities. Periodic on-line pressure pulses or backflow can be effective if the capability is carefully incorporated at the design time. Blowdown capability is always incorporated into steam generators or evaporators to control the accumulation of non-volatile impurities the cause or aggreviate fouling. Low-fouling surfaces (for example, very smooth, implanted with ions, or of low surface energy like Teflon) are an option for some applications. Modern components are typically required to be designed for ease of inspection of internals and periodic cleaning. Chemical or mechanical cleaning processes for the removal of deposits and scales are recommended when fouling reaches the point of impacting the system performance. These processes comprise pickling with acids and metal complexing agents, cleaning with high-velocity water jets ("water lancing"), or recirculating sponge rubber balls. Whereas chemical cleaning causes environmental problems through the handling, application, storage and disposal of chemicals, the mechanical cleaning by means of circulating cleaning balls can be a more environmentally-friendly alternative. Also ultrasonic or abrasive cleaning methods are available for many specific applications. # External links - On-line & In-situ fouling/biofilm/scales/slime monitoring - A 'green' Antifouling alternative to Chlorine	https://www.wikidoc.org/index.php/Fouling
a5e48df1bc72c91e7f0ca1520db4c721f24147f7	wikidoc	Nitrile	Nitrile A nitrile is any organic compound which has a -C≡N functional group. The -C≡N functional group is called a nitrile group. In the -CN group, the carbon atom and the nitrogen atom are triple bonded together. The prefix cyano is used in chemical nomenclature to indicate the presence of a nitrile group in a molecule. A cyanide ion is a negative ion with the formula CN−. The -CN group is sometimes, less properly, referred to as a cyanide group or cyano group and compounds with them are sometimes referred to as cyanides. Nitriles sometimes release the highly toxic CN− cyanide ion. See the article on cyanide for a discussion of biological effects and toxicity. # History Hydrogen cyanide was first synthesized by K.W. Scheele in 1782 and he was killed in an attempt to get the anhydrous compound . J. L. Gay-Lussac was the first to prepare the pure acid in 1811 and Friedrich Wohler and Justus von Liebig were the first to prepare the first nitriles benzoyl cyanide and benzonitrile in 1832. Théophile-Jules Pelouze synthesized propionitrile in 1834. # Synthesis of nitriles Nitriles can be prepared in organic synthesis by the following methods: - Nucleophilic aliphatic substitution reactions of alkyl halides with metal cyanides. - dehydration of primary amides. Many reagents are available, the combination of ethyl dichlorophosphate and DBU just one of them in this conversion of benzamide to benzonitrile: - dehydration of secondary amides (von Braun amide degradation) - dehydration of aldoximes with triethylamine/sulfur dioxide, zeolites, or sulfuryl chloride - One-pot synthesis of aldehyde with hydroxylamine and sodium sulfate. - reaction of metal cyanides with aldehydes in the cyanohydrin reaction - from aryl carboxylic acids (Letts nitrile synthesis) - aromatic nitriles from diazonium compounds in the Sandmeyer reaction - from alkenes and alkynes in hydrocyanation - A commercial source for the cyanide group is diethylaluminum cyanide Et2AlCN which can be prepared from triethylaluminium and HCN . It has been used in nucleophilic addition to ketones. For an example of its use see: Kuwajima Taxol total synthesis - cyanide ions facilitate the coupling of dibromides. Reaction of α,α'-dibromo adipic acid with sodium cyanide in ethanol yields the cyano cyclobutane: # Reactions of nitriles Nitrile groups in organic compounds can undergo various reactions when subject to certain reactants or conditions. A nitrile group can be hydrolyzed, reduced, or ejected from a molecule as a cyanide ion. - In hydrolysis the nitrile is reacted with an acid and water at a high temperature, or with a base and water. The acid hydrolysis forms a carboxylic acid, the alkali hydrolysis forms a carboxylate. - In organic reduction the nitrile is reduced by reacting it with hydrogen with a nickel catalyst; an amine is formed in this reaction. Reduction to the imine followed by hydrolysis to the aldehyde takes place in the Stephen aldehyde synthesis - A nitrile is an electrophile at the carbon atom in a nucleophilic addition reactions: with an organozinc compound in the Blaise reaction and with alcohols in the Pinner reaction. likewise, the reaction of the amine sarcosine with cyanamide yields creatine - with an organozinc compound in the Blaise reaction - and with alcohols in the Pinner reaction. - likewise, the reaction of the amine sarcosine with cyanamide yields creatine - In reductive decyanation the nitrile group is replaced by a proton . An effective decyanation is by a dissolving metal reduction with HMPA and potassium metal in tert-butyl alcohol. α-Amino-nitriles can be decyanated with lithium aluminium hydride. - Nitriles self-react in presence of base in the Thorpe reaction in a nucleophilic addition - In organometallic chemistry nitriles are known to add to alkynes in carbocyanation:	Nitrile A nitrile is any organic compound which has a -C≡N functional group. The -C≡N functional group is called a nitrile group. In the -CN group, the carbon atom and the nitrogen atom are triple bonded together. The prefix cyano is used in chemical nomenclature to indicate the presence of a nitrile group in a molecule. A cyanide ion is a negative ion with the formula CN−. The -CN group is sometimes, less properly, referred to as a cyanide group or cyano group and compounds with them are sometimes referred to as cyanides. Nitriles sometimes release the highly toxic CN− cyanide ion. See the article on cyanide for a discussion of biological effects and toxicity. # History Hydrogen cyanide was first synthesized by K.W. Scheele in 1782 and he was killed in an attempt to get the anhydrous compound [1]. J. L. Gay-Lussac was the first to prepare the pure acid in 1811 and Friedrich Wohler and Justus von Liebig were the first to prepare the first nitriles benzoyl cyanide and benzonitrile in 1832. Théophile-Jules Pelouze synthesized propionitrile in 1834. # Synthesis of nitriles Nitriles can be prepared in organic synthesis by the following methods: - Nucleophilic aliphatic substitution reactions of alkyl halides with metal cyanides. - dehydration of primary amides. Many reagents are available, the combination of ethyl dichlorophosphate and DBU just one of them in this conversion of benzamide to benzonitrile:[2] - dehydration of secondary amides (von Braun amide degradation) - dehydration of aldoximes with triethylamine/sulfur dioxide, zeolites, or sulfuryl chloride - One-pot synthesis of aldehyde with hydroxylamine and sodium sulfate. - reaction of metal cyanides with aldehydes in the cyanohydrin reaction - from aryl carboxylic acids (Letts nitrile synthesis) - aromatic nitriles from diazonium compounds in the Sandmeyer reaction - from alkenes and alkynes in hydrocyanation - A commercial source for the cyanide group is diethylaluminum cyanide Et2AlCN which can be prepared from triethylaluminium and HCN [4]. It has been used in nucleophilic addition to ketones.[5] For an example of its use see: Kuwajima Taxol total synthesis - cyanide ions facilitate the coupling of dibromides. Reaction of α,α'-dibromo adipic acid with sodium cyanide in ethanol yields the cyano cyclobutane:[6] # Reactions of nitriles Nitrile groups in organic compounds can undergo various reactions when subject to certain reactants or conditions. A nitrile group can be hydrolyzed, reduced, or ejected from a molecule as a cyanide ion. - In hydrolysis the nitrile is reacted with an acid and water at a high temperature, or with a base and water. The acid hydrolysis forms a carboxylic acid, the alkali hydrolysis forms a carboxylate. - In organic reduction the nitrile is reduced by reacting it with hydrogen with a nickel catalyst; an amine is formed in this reaction. Reduction to the imine followed by hydrolysis to the aldehyde takes place in the Stephen aldehyde synthesis - A nitrile is an electrophile at the carbon atom in a nucleophilic addition reactions: with an organozinc compound in the Blaise reaction and with alcohols in the Pinner reaction. likewise, the reaction of the amine sarcosine with cyanamide yields creatine [8] - with an organozinc compound in the Blaise reaction - and with alcohols in the Pinner reaction. - likewise, the reaction of the amine sarcosine with cyanamide yields creatine [8] - In reductive decyanation the nitrile group is replaced by a proton [9]. An effective decyanation is by a dissolving metal reduction with HMPA and potassium metal in tert-butyl alcohol. α-Amino-nitriles can be decyanated with lithium aluminium hydride. - Nitriles self-react in presence of base in the Thorpe reaction in a nucleophilic addition - In organometallic chemistry nitriles are known to add to alkynes in carbocyanation:[10]	https://www.wikidoc.org/index.php/Franchimont_reaction
fe31ea4688fa5e18a1ce7227c1d52c76e4c77d4d	wikidoc	Freckle	Freckle # Overview Freckles are small colored spots of melanin on the exposed skin or membrane of people with complexions fair enough for them to be visible. Having freckles is genetic and is related to the presence of the melanocortin-1 receptor MC1R gene variant, which is dominant. Freckling can also be triggered by long exposure to sunlight, such as suntanning. When the sun’s rays penetrate the skin, they activate melanocytes which can cause freckles to become darker and more numerous, although the distribution of melanin is not the same. Fair hair such as blonde, or more commonly red hair, are usually common with the genetic factor of freckles, but none so much as fair or pale skin. Freckles are predominantly found on the face, although they may appear on any skin exposed to the sun. Freckles are rare on infants, and more common on children before puberty; they are less common on adults. Children who do not produce enough melanin to protect their skin against harmful rays from the sun develop temporary freckles associated with childhood that usually go away upon puberty, once more melanin is produced. People with the fairest skin often do not produce enough melanin, and so freckles are present after puberty and into adulthood, indicating that individual as a genetic carrier for freckles. Upon exposure to the sun, freckles will reappear if they have been altered with creams or lasers and not protected from the sun, but do however fade with age in some cases. Freckles are not a skin disorder. People with a predisposition to freckles may be especially susceptible to sunburn and skin cancer, and should therefore take extra care to protect themselves in the sun with a daily sunblock of at least 15 SPF. During the Middle Ages and up until the early 15th century in Europe, an excess of freckles ("witchmarks" or "witchspots") became associated with witchcraft and witche, most likely because of genetic pairing with red hair, also considered to be a quality of witches. ## Two types of freckles Ephelides is a genetic trait. It’s used to describe a freckle that is flat, light brown or red, and fades in the winter. Ephelides are more common in those with light complexions and with the regular use of sunblock, can be suppressed. Liver spot (also known as sun spots) are freckles that do not fade in the winter. Rather, they form after years of exposure to the sun. Lentigines are more common in older people.	Freckle Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] # Overview Freckles are small colored spots of melanin on the exposed skin or membrane of people with complexions fair enough for them to be visible. Having freckles is genetic and is related to the presence of the melanocortin-1 receptor MC1R gene variant, which is dominant. Freckling can also be triggered by long exposure to sunlight, such as suntanning. When the sun’s rays penetrate the skin, they activate melanocytes which can cause freckles to become darker and more numerous, although the distribution of melanin is not the same. Fair hair such as blonde, or more commonly red hair, are usually common with the genetic factor of freckles, but none so much as fair or pale skin. Freckles are predominantly found on the face, although they may appear on any skin exposed to the sun. Freckles are rare on infants, and more common on children before puberty; they are less common on adults. Children who do not produce enough melanin to protect their skin against harmful rays from the sun develop temporary freckles associated with childhood that usually go away upon puberty, once more melanin is produced. People with the fairest skin often do not produce enough melanin, and so freckles are present after puberty and into adulthood, indicating that individual as a genetic carrier for freckles. Upon exposure to the sun, freckles will reappear if they have been altered with creams or lasers and not protected from the sun, but do however fade with age in some cases. Freckles are not a skin disorder. People with a predisposition to freckles may be especially susceptible to sunburn and skin cancer, and should therefore take extra care to protect themselves in the sun with a daily sunblock of at least 15 SPF. During the Middle Ages and up until the early 15th century in Europe, an excess of freckles ("witchmarks" or "witchspots") became associated with witchcraft and witche, most likely because of genetic pairing with red hair, also considered to be a quality of witches.[1] ## Two types of freckles Ephelides is a genetic trait. It’s used to describe a freckle that is flat, light brown or red, and fades in the winter. Ephelides are more common in those with light complexions and with the regular use of sunblock, can be suppressed. Liver spot (also known as sun spots) are freckles that do not fade in the winter. Rather, they form after years of exposure to the sun. Lentigines are more common in older people.	https://www.wikidoc.org/index.php/Freckle
5de78dcef79b583a99a22d5638b6ef1d4aa239cd	wikidoc	Fructan	Fructan A fructan is a polymer of fructose molecules. They occur in foods such as: - Artichokes - Asparagus - Green beans - Leeks - Onions (including spring onion) - Wheat In animal fodder, fructans also appear in grass, with dietary implications for horses and other equidae. There are 3 types of fructans: - Inulin - linear fructans generally linked by β(2→1) glycosidic bonds - Levan - linear fructans generally linked by β(2→6) glycosidic bonds - Graminan - branched fructans linked by both β(2→1) and β(2→6) glycosidic bonds # Fructan content of various foods Artichoke, Jerusalem: 16.0-20.0% Artichoke, Globe: 2.0-6.8% Asparagus: 1.4-4.1% Barley kernels (very young): 22% Cheese spread: 4.5% Chocolate: 9.4% Onion: 1.1-10.1% Rye bran: 7% Rye grain: 4.6-6.6% Wheat flour: 1-4% Pasta: 1-4% White bread: 0.7-2.8% # Functions Plants storing their food as fructans are able to thrive at low temperatures since fructans confer tolerance to freezing. They bind to membranes, thereby helping to keep cells intact.	Fructan A fructan is a polymer of fructose molecules. They occur in foods such as: - Artichokes - Asparagus - Green beans - Leeks - Onions (including spring onion) - Wheat In animal fodder, fructans also appear in grass, with dietary implications for horses and other equidae. There are 3 types of fructans: - Inulin - linear fructans generally linked by β(2→1) glycosidic bonds - Levan - linear fructans generally linked by β(2→6) glycosidic bonds - Graminan - branched fructans linked by both β(2→1) and β(2→6) glycosidic bonds # Fructan content of various foods Artichoke, Jerusalem: 16.0-20.0%[1] Artichoke, Globe: 2.0-6.8%[1] Asparagus: 1.4-4.1%[1] Barley kernels (very young): 22%[2] Cheese spread: 4.5%[3] Chocolate: 9.4%[3] Onion: 1.1-10.1%[1] Rye bran: 7%[4] Rye grain: 4.6-6.6%[4] Wheat flour: 1-4%[2] Pasta: 1-4%[1] White bread: 0.7-2.8%[1] # Functions Plants storing their food as fructans are able to thrive at low temperatures since fructans confer tolerance to freezing. They bind to membranes, thereby helping to keep cells intact.	https://www.wikidoc.org/index.php/Fructan
7c894ea3fff85186456959a198ba43cdf2a569eb	wikidoc	Ketosis	Ketosis # Overview Ketosis (IPA pronunciation: Template:IPA) is a stage in metabolism occurring when the liver converts fat into fatty acids and ketone bodies which can be used by the body for energy. # Historical Perspective It was identified by Dr. Stephen Moody in 1969. # Pathophysiology Adipose tissue consists of highly specialized cells which store energy in the form of a triglyceride and release it upon hydrolysis in a process known as lipolysis, yielding three fatty acids and one glycerol molecule. Ketosis is the accumulation of excessive keto acids in the blood stream (specifically acetoacetate and beta-hydroxy butyrate), these ketone bodies are a by-product of the lipid metabolic pathway after the fat is converted to energy. Most medical resources regard ketosis as a physiological state associated with chronic starvation. Glucose is regarded as the preferred energy source for all cells in the body with ketosis being regarded as a crisis reaction of the body to a lack of carbohydrates in the diet. In recent years this viewpoint, both the body's preference for glucose and the dangers associated with ketosis, has been challenged by some doctors. Ketone bodies, from the breakdown of fatty acids to acetyl groups, are also produced during this state, and are burned throughout the body. Excess ketone bodies will slowly decarboxylate into acetone. That molecule is excreted in the breath and urine. When glycogen stores are not available in the cells (glycogen is primarily created when carbohydrates such as starch and sugar are consumed in the diet), fat (triacylglycerol) is cleaved to give 3 fatty acid chains and 1 glycerol molecule in a process called lipolysis. Most of the body is able to utilize fatty acids as an alternative source of energy in a process where fatty acid chains are cleaved to form acetyl-CoA, which can then be fed into the Krebs Cycle. During this process a high concentration of glucagon is present in the serum and this inactivates hexokinase and phosphofructokinase-1 (regulators of glycolysis) indirectly, causing most cells in the body to use fatty acids as their primary energy source. At the same time, glucose is synthesized in the liver from lactic acid, glucogenic amino acids, and glycerol, in a process called gluconeogenesis. This glucose is used exclusively for energy by cells such as neurons and red blood cells. # Differentiation of Ketosis from other Disorders Ketosis should not be confused with ketoacidosis (diabetic ketoacidosis or the less common alcoholic ketoacidosis), which is severe ketosis causing the pH of the blood to drop below 7.2. Ketoacidosis is a medical condition usually caused by diabetes and accompanied by dehydration, hyperglycemia, ketonuria and increased levels of glucagon. The high glucagon, low insulin serum levels signals the body to produce more glucose via gluconeogenesis, glycogenolysis and ketogenesis. High levels of glucose causes the failure of tubular reabsorption in the kidneys, causing water to leak into the tubules in a process called osmotic diuresis, causing dehydration and further exacerbating the acidosis. Since non-medically trained people often confuse ketosis with ketoacidosis, Dr Robert Atkins proposed that ketosis that occurs through deliberate carbohydrate restriction be referred to as "benign dietary ketosis." # Diet If the diet is changed from a highly glycemic diet to a diet that does not substantially contribute to blood glucose, the body goes through a set of stages to enter ketosis. During the initial stages of this process the adult brain does not burn ketones, however the newborn brain makes immediate use of this important substrate for lipid synthesis in the brain. After about 48 hours of this process, the adult brain starts burning ketones in order to more directly utilize the energy from the fat stores that are being depended upon, and to reserve the glucose only for its absolute needs, thus avoiding the depletion of the body's protein store in the muscles. Whether ketosis takes place can be checked by using special urine test strips such as Ketostix. Deliberately induced ketosis through a low-carbohydrate diet has been used to treat medical conditions although most such treatments remain controversial. The ketogenic diet is an approach to treating epilepsy, and the Atkins Nutritional Approach (and many similar diets) is marketed for treating obesity. The very low calorie, medically supervised Bernstein, Lighter Life, Cambridge Diet, Lindora diets and Medifast also use ketosis for weight loss. It must be noted that the Lighter Life and the Cambridge diet are the same. # See Also - Ketoacidosis - Ketogenic diet - Ketonuria - Low-carbohydrate diet	Ketosis Editor-In-Chief: C. Michael Gibson, M.S., M.D. [4] # Overview Ketosis (IPA pronunciation: Template:IPA) is a stage in metabolism occurring when the liver converts fat into fatty acids and ketone bodies which can be used by the body for energy. # Historical Perspective It was identified by Dr. Stephen Moody in 1969. # Pathophysiology Adipose tissue consists of highly specialized cells which store energy in the form of a triglyceride and release it upon hydrolysis in a process known as lipolysis, yielding three fatty acids and one glycerol molecule.[1] Ketosis is the accumulation of excessive keto acids in the blood stream (specifically acetoacetate and beta-hydroxy butyrate), these ketone bodies are a by-product of the lipid metabolic pathway after the fat is converted to energy.[2] [3] [4] [5] [6] Most medical resources regard ketosis as a physiological state associated with chronic starvation. Glucose is regarded as the preferred energy source for all cells in the body with ketosis being regarded as a crisis reaction of the body to a lack of carbohydrates in the diet. In recent years this viewpoint, both the body's preference for glucose and the dangers associated with ketosis, has been challenged by some doctors.[7][8][9] Ketone bodies, from the breakdown of fatty acids to acetyl groups, are also produced during this state, and are burned throughout the body. Excess ketone bodies will slowly decarboxylate into acetone. That molecule is excreted in the breath and urine. When glycogen stores are not available in the cells (glycogen is primarily created when carbohydrates such as starch and sugar are consumed in the diet), fat (triacylglycerol) is cleaved to give 3 fatty acid chains and 1 glycerol molecule in a process called lipolysis. Most of the body is able to utilize fatty acids as an alternative source of energy in a process where fatty acid chains are cleaved to form acetyl-CoA, which can then be fed into the Krebs Cycle. During this process a high concentration of glucagon is present in the serum and this inactivates hexokinase and phosphofructokinase-1 (regulators of glycolysis) indirectly, causing most cells in the body to use fatty acids as their primary energy source. At the same time, glucose is synthesized in the liver from lactic acid, glucogenic amino acids, and glycerol, in a process called gluconeogenesis. This glucose is used exclusively for energy by cells such as neurons and red blood cells. # Differentiation of Ketosis from other Disorders Ketosis should not be confused with ketoacidosis (diabetic ketoacidosis or the less common alcoholic ketoacidosis), which is severe ketosis causing the pH of the blood to drop below 7.2. Ketoacidosis is a medical condition usually caused by diabetes and accompanied by dehydration, hyperglycemia, ketonuria and increased levels of glucagon. The high glucagon, low insulin serum levels signals the body to produce more glucose via gluconeogenesis, glycogenolysis and ketogenesis. High levels of glucose causes the failure of tubular reabsorption in the kidneys, causing water to leak into the tubules in a process called osmotic diuresis, causing dehydration and further exacerbating the acidosis. Since non-medically trained people often confuse ketosis with ketoacidosis, Dr Robert Atkins proposed that ketosis that occurs through deliberate carbohydrate restriction be referred to as "benign dietary ketosis." # Diet If the diet is changed from a highly glycemic diet to a diet that does not substantially contribute to blood glucose, the body goes through a set of stages to enter ketosis. During the initial stages of this process the adult brain does not burn ketones, however the newborn brain makes immediate use of this important substrate for lipid synthesis in the brain. After about 48 hours of this process, the adult brain starts burning ketones in order to more directly utilize the energy from the fat stores that are being depended upon, and to reserve the glucose only for its absolute needs, thus avoiding the depletion of the body's protein store in the muscles. Whether ketosis takes place can be checked by using special urine test strips such as Ketostix. Deliberately induced ketosis through a low-carbohydrate diet has been used to treat medical conditions although most such treatments remain controversial.[10] [11] The ketogenic diet is an approach to treating epilepsy, and the Atkins Nutritional Approach (and many similar diets) is marketed for treating obesity. The very low calorie, medically supervised Bernstein, Lighter Life, Cambridge Diet, Lindora diets and Medifast also use ketosis for weight loss. [5][6] [7] It must be noted that the Lighter Life and the Cambridge diet are the same. # See Also - Ketoacidosis - Ketogenic diet - Ketonuria - Low-carbohydrate diet	https://www.wikidoc.org/index.php/Fruity_smell_to_breath
fccee2b56b2db736807cbb5acaecbabf40d2119f	wikidoc	Fucales	Fucales Fucales is an order in the Phylum Phaeophyta or Brown algae. Members of this order are fucoids. The list of families (see box at right) in Fucales, as well as additional taxonomic information on algae, is publicly accessible at Algaebase. The Class Phaeophyceae is included within the Division Heterokontophyta. This name comes from the Greek word phaios meaning "brown" and phyton meaning plant. They include some of the largest plants in the sea, some however are small and fine in structure. # Classification The Class Phaeophyceae is devided into the following orders (Hoek, 1995). - Ectocarpales - Sphacelariales - Syringodermatales - Dictyotales - Scytosiphonales - Cutleriales - Dictyosiphonales - Chordariales - Sporochnales - Desmarestiales - Laminariales - Fucales Fucus - Durvillaeales - Ascoseirales The Fucales include some of the more common littoral seaweeds and the members of the order have the typical seaweed construction: a holdfast, stipe and lamina. The lamina is often much branched and may include gas filled bladders. Growth is by division of the apical cells. They are oogamous where there is fusion between the small male gamete and the large female gamete. As their general name suggests their pigmentation is brown. All species are multicellular. Full details of the characteristics are complex and consist of details of the flagella, shape of the chloroplasts, structure of the cell walls and details of the life-cycle. # Numbers There are about 1,500 - 2,000 species of brown seaweeds world-wide.	Fucales Fucales is an order in the Phylum Phaeophyta or Brown algae. Members of this order are fucoids. The list of families (see box at right) in Fucales, as well as additional taxonomic information on algae, is publicly accessible at Algaebase. [1] [1] The Class Phaeophyceae is included within the Division Heterokontophyta.[2] This name comes from the Greek word phaios meaning "brown" and phyton meaning plant.[3] They include some of the largest plants in the sea, some however are small and fine in structure. # Classification The Class Phaeophyceae is devided into the following orders (Hoek, 1995). [4] - Ectocarpales - Sphacelariales - Syringodermatales - Dictyotales - Scytosiphonales - Cutleriales - Dictyosiphonales - Chordariales - Sporochnales - Desmarestiales - Laminariales - Fucales **Fucus - Durvillaeales - Ascoseirales The Fucales include some of the more common littoral seaweeds and the members of the order have the typical seaweed construction: a holdfast, stipe and lamina. The lamina is often much branched and may include gas filled bladders. Growth is by division of the apical cells. They are oogamous where there is fusion between the small male gamete and the large female gamete. As their general name suggests their pigmentation is brown. All species are multicellular. Full details of the characteristics are complex and consist of details of the flagella, shape of the chloroplasts, structure of the cell walls and details of the life-cycle. [4] # Numbers There are about 1,500 - 2,000 species of brown seaweeds world-wide.[5]	https://www.wikidoc.org/index.php/Fucales
21bd4ea1b4eb32d55dc79ed68cefa4b568e4f594	wikidoc	Fukutin	Fukutin Fukutin is a eukaryotic protein necessary for the maintenance of muscle integrity, cortical histogenesis, and normal ocular development. Mutations in the fukutin gene have been shown to result in Fukuyama congenital muscular dystrophy (FCMD) characterised by brain malformation - one of the most common autosomal-recessive disorders in Japan. In humans this protein is encoded by the FCMD gene (also named FKTN), located on chromosome 9q31. Human fukutin exhibits a length of 461 amino acids and a predicted molecular mass of 53.7 kDa. # Function Although its function is mostly unknown, fukutin is a putative transmembrane protein that is ubiquitously expressed, although at higher levels in skeletal muscle, heart and brain. It is localized to the cis-Golgi compartment, where it may be involved in the glycosylation of α-dystroglycan in skeletal muscle. The encoded protein is thought to be a glycosyltransferase and could play a role in brain development. # Clinical significance Defects in this gene are a cause of Fukuyama congenital muscular dystrophy (FCMD), Walker-Warburg syndrome (WWS), limb-girdle muscular dystrophy type 2M (LGMD2M), and dilated cardiomyopathy type 1X (CMD1X).	Fukutin Fukutin is a eukaryotic protein necessary for the maintenance of muscle integrity, cortical histogenesis, and normal ocular development. Mutations in the fukutin gene have been shown to result in Fukuyama congenital muscular dystrophy (FCMD) characterised by brain malformation - one of the most common autosomal-recessive disorders in Japan.[1] In humans this protein is encoded by the FCMD gene (also named FKTN), located on chromosome 9q31.[2][3][4] Human fukutin exhibits a length of 461 amino acids and a predicted molecular mass of 53.7 kDa. # Function Although its function is mostly unknown, fukutin is a putative transmembrane protein that is ubiquitously expressed, although at higher levels in skeletal muscle, heart and brain.[5] It is localized to the cis-Golgi compartment, where it may be involved in the glycosylation of α-dystroglycan in skeletal muscle. The encoded protein is thought to be a glycosyltransferase and could play a role in brain development.[3] # Clinical significance Defects in this gene are a cause of Fukuyama congenital muscular dystrophy (FCMD), Walker-Warburg syndrome (WWS), limb-girdle muscular dystrophy type 2M (LGMD2M), and dilated cardiomyopathy type 1X (CMD1X).[3][6]	https://www.wikidoc.org/index.php/Fukutin
25ad71e76039950311953693dac69e9d7afbc60c	wikidoc	Funeral	Funeral # Overview A funeral is a ceremony marking a person's death. Funerary customs comprise the complex of beliefs and practices used by a culture to remember the dead, from the funeral itself, to various monuments, prayers, and rituals undertaken in their honor. These customs vary widely between cultures, and between religious affiliations within cultures. In some cultures the dead are venerated; this is commonly called ancestor worship. The word funeral comes from the Latin funus, which had a variety of meanings, including the corpse and the funerary rites themselves. Funeral rites are as old as the human race itself, as well as other hominids. For example, in the Shanidar cave in Iraq, Neanderthal skeletons have been discovered with a characteristic layer of pollen, which suggests that Neanderthals buried the dead with gifts of flowers. This has been interpreted as suggesting that Neanderthals believed in an afterlife, and in any case were aware of their own mortality and were capable of mourning. # Religious funerals ## Jewish funerals ## Buddhist funerals ## Catholic Christian funerals ## Hindu funerals ## Islamic funerals ## Sikh funerals In Sikhism death is considered a natural process. An event that has absolute certainty and only happens as a direct result of God's Will or Hukam. To a Sikh, birth and death are closely associated, because they are both part of the cycle of human life of "coming and going" ( ਆਵਣੁ ਜਾਣਾ , Aana Jaana) which is seen as transient stage towards Liberation ( ਮੋਖੁ ਦੁਆਰੁ , Mokh Du-aar), complete unity with God. Sikhs thus believe in reincarnation. However, by contrast, the soul itself is not subject to the cycle of birth and death. Death is only the progression of the soul on its journey from God, through the created universe and back to God again. In life, a Sikh always tries to constantly remember death so that he or she may be sufficiently prayerful, detached and righteous to break the cycle of birth and death and return to God. The public display of grief at the funeral or Antam Sanskar as it is called in the Sikh culture, such as wailing or crying out loud is discouraged and should be kept to a minimum. Cremation is the preferred method of disposal, although if this is not possible any other methods such as burial or submergence at sea are acceptable. Worship of the dead with gravestones, etc. is discouraged, because the body is considered to be only the shell and the person's soul is their real essence. On the day of the cremation, the body is taken to the Gurdwara or home where hymns (Shabads) from the Guru Granth Sahib, the Sikh Scriptures are recited by the congregation, which induce feeling of consolation and courage. Kirtan may also be performed by Ragis while the relatives of the deceased recite "Waheguru" sitting near the coffin. This service normally takes from 30 to 60 minutes. At the conclusion of the service, an Ardas is said before the coffin is taken to the cremation site. At the point of cremation, a few more Shabads may be sung and final speeches are made about the deceased person. Then the Kirtan Sohila, night time prayer is recited and finally Ardas called the "Antim Ardas" ("Final Prayer") is offered. The eldest son or a close relative generally starts the cremation process – light the fire or press the button for the burning to begin. This service usually lasts about 30 to 60 minutes. The ashes are later collected and disposed by immersing them in the nearest river. Sikhs do not erect monuments over the remains of the dead. After the cremation ceremony, there may be another service at the Gurdwara, the Sikh place of worship, call the Sahaj Paath Bhog Ceremony but this is optional. # Funerals in Japan # Funerals in contemporary North America ## Traditional funerals Within the United States and Canada, in most cultural groups and regions, the funeral rituals can be divided into three parts: visitation, funeral, and the burial service. ### Visitation At the visitation (also called a "viewing" or "wake") the body of the deceased person (or decedent) is placed on display in the casket (also called a coffin, however almost all body containers are caskets). The viewing often takes place on one or two evenings before the funeral. The body is traditionally dressed in the decedent's best clothes. In recent times there has been more variation in what the decedent is dressed in - some people choose to be dressed in clothing more reflective of how they dressed in life. The body will often be adorned with the usual jewelry, including a watch. The jewelry and watch could be taken off and given to the family of the deceased, or remain in the casket after burial, but it most likely will be removed before cremation. The body may or may not be embalmed, depending upon such factors as the amount of time since the death has occurred, religious practices, or requirements of the place of burial. The only prescribed aspects of this gathering are that frequently the attendees sign a book kept by the deceased's survivors to record who attended and that the attendees are expected to view the deceased's body in the coffin. In addition, a family may choose to display photographs taken of the deceased person during his/her life (often, formal portraits with other family members and candid pictures to show "happy times"), prized possessions and other items representing his/her hobbies and/or accomplishments. A more recent trend is to create a DVD with pictures and video of the deceased, accompanied by music, and play this DVD continuously during the visitation. The viewing is either "open casket", in which the embalmed body of the deceased has been clothed and treated with cosmetics for display; or "closed casket", in which the coffin is closed. The coffin may be closed if the body was too badly damaged because of an accident or fire or other trauma, deformed from illness or if someone in the group is emotionally unable to cope with viewing the corpse. During an open casket. However, this step is foreign to Judaism; Jewish funerals are held soon after death, and the corpse is never displayed. As well, Jewish law forbids anyone to embalm the body of the deceased. Traditionally flowers (and music) are not sent to a grieving Jewish family as it is a reminder of the life that is now lost.(See also Jewish bereavement.) The decedent's closest friends and relatives who are unable to attend frequently send flowers to the viewing, with the exception of a Jewish Funeral , where flowers would not be appropriate (and donations are given to a charity instead). The viewing typically takes place at a funeral home, which is equipped with gathering rooms where the viewing can be conducted, although the viewing may also take place at a church. In earlier history, it was common practice in some of the states in the southeastern United States that the body was taken to the decedent’s home or that of a relative for viewing. The viewing may end with a prayer service; in the Catholic funeral, this may include a rosary. A visitation is often held the evening before the day of the funeral. However, when the deceased person is elderly the visitation may be held immediately preceding the funeral. This allows elderly friends of the deceased a chance to view the body and attend the funeral in one trip, since it may be difficult for them to arrange travel; this step may also be taken if the deceased has few survivors or the survivors want a funeral with only a small number guests. A traditional Fire Department funeral consists of two raised aerial ladders. The firefighter(s) travel under the aerials on their ride on the fire apparatus to the cemetery. ### Funeral A memorial service, often called a funeral and often officiated by clergy from the decedent's or bereaved's church or religion. A funeral may take place at either a funeral home or church. A funeral is held according to the family's choosing which may be a few days after the time of death, allowing family members to attend the service. The deceased is usually transported from the funeral home to a church in a hearse, a specialized vehicle designed to carry casketed remains. The deceased is often transported in a procession, with the hearse, funeral service vehicles, and private automobiles traveling in a procession to the church or other location where the services will be held. In a number of jurisdictions, special laws cover funeral processions - such as requiring other vehicles to give right-of-way to a funeral procession. Funeral service vehicles may be equipped with light bars and special flashers to increase their visibility on the roads. After the funeral service, if the deceased is to be buried the funeral procession will proceed to a cemetery if not already there. If the deceased is to be cremated the funeral procession may then proceed to the crematory. Funeral services include prayers; readings from the Bible or other sacred texts; hymns (sung either by the attendees or a hired vocalist); and words of comfort by the clergy. Frequently, a relative or close friend will be asked to give a eulogy, which details happy memories and accomplishments; often commenting on the deceased's flaws, especially at length, is considered impolite. Sometimes the delivering of the eulogy is done by the clergy. Clergy are often asked to deliver eulogies for people they have never met. Church bells may also be tolled both before and after the service. Tradition also allows the attendees of the memorial service to have one last opportunity to view the decedent's body and say good-bye; the immediate family (siblings (and their spouses); followed by the decedent's spouse, parents and children) are always the very last to view their loved one before the coffin is closed. This opportunity can take place immediately before the service begins, or at the very end of the service. During the funeral and at the burial service, the casket may be covered with a large arrangement of flowers, called a casket spray. If the decedent served in a branch of the Armed forces, the casket may be covered with a national flag; however nothing should cover the national flag according to Title 4, United States Code, Chapter 1, Paragraph 8i. Funeral customs vary from country to country. In the United States, any type of noise other than quiet whispering or mourning is considered disrespectful. Note: In some religious denominations, for example, Roman Catholic and Anglican, eulogies are prohibited or discouraged during this service, in order to preserve respect for traditions. Also, for these religions, the coffin is traditionally closed at the end of the wake and is not re-opened for the funeral service. ### Burial service A burial service, conducted at the side of the grave, tomb, mausoleum or crematorium, at which the body of the decedent is buried or cremated at the conclusion. Sometimes, the burial service will immediately follow the funeral, in which case a funeral procession travels from the site of the memorial service to the burial site. Other times, the burial service takes place at a later time, when the final resting place is ready. If the decedent served in a branch of the Armed forces, military rites are often accorded at the burial service. In many religious traditions, pallbearers, usually males who are close, but not immediate relatives (such as cousins, nephews or grandchildren) or friends of the decedent, will carry the casket from the chapel (of a funeral home or church) to the hearse, and from the hearse to the site of the burial service. The pallbearers often sit in a special reserved section during the memorial service. According to most religions, coffins are kept closed during the burial ceremony. In Eastern Orthodox funerals, the coffins are reopened just before burial to allow loved ones to look at the deceased one last time and give their final farewells. The morticians will typically ensure that all jewelry, including wristwatch, that were displayed at the wake are in the casket before it is buried or entombed. It would be unseemly to have the decedent's heirs squabbling over a Rolex or an engagement ring. Custom requires that everything goes into the ground. There is an exception, in the case of cremation. Such items tend to melt or suffer damage, so they are usually removed before the body goes into the furnace. Pacemakers are removed prior to cremation - if they were left in they could possibly explode and damage the crematorium. ### Luncheon In many traditions, a meal or other gathering often follows the burial service. This gathering may be held at the decedent's church or another off-site location. Some funeral homes have large spaces set aside to provide funeral dinners. ### Etiquette Generally speaking, the number of people who are considered obliged to attend each of these three rituals by etiquette decreases at each step: - Distant relatives and acquaintances may be called upon to attend the visitation. - The decedent's closer relatives and local friends attend the funeral or memorial service, and subsequent burial (if it is held immediately after the memorial service). - If the burial is on the day of the funeral, only the decedent's closest relatives and friends attend the burial service (although if the burial service immediately follows the funeral, all attendees of the memorial service are asked to attend). Traditionally etiquette dictated that the bereaved and other attendees at a funeral wear semi-formal clothing—such as a suit and tie for men or a dress for women. The most traditional and respectful color is solid black (with a matching solid black tie for men) preferably without any underlying pinstripes or patterns in the weave. But failing that charcoal gray or dark navy blue may be worn. Wearing short skirts, low-cut tops, t-shirts with advertising slogans or suggestive images, or, at Western funerals, a large amount of white (other than a button-down shirt or blouse, or a military uniform) is often seen as disrespectful. Women who are grieving the death of their husband or a close partner sometimes wear a veil to conceal the face, although the veil is not common now. Increasingly, the deceased have requested before their death that the attendees of their funeral should wear something of their favorite colour or wear something specific (namely a football shirt). They do this as the black did not reflect their outgoing personality. ## Private services On occasion, the family of the deceased may wish to have only a very small service, with just the deceased's closest family members and friends attending. This type of ceremony means it is closed to the public. One may only go to the funeral if one is invited. In this case, a private funeral service is conducted. Reasons vary but often include the following: - The deceased was an infant (possibly, they may have been stillborn) or very aged, and therefore has few surviving family members or friends. - The deceased may be a crime victim or a convicted criminal who was serving a prison sentence. In this case, the service is made private either to avoid unwanted media coverage (especially with a crime victim); or to avoid unwanted intrusion (especially if the deceased was convicted of murder or sexual assault). - The family does not feel able to endure a traditional service (due to emotional shock) or simply wants a quiet, simple funeral with only the most important people of the deceased's life in attendance. - The family and/or the deceased, as more frequently preplanned, prefer simplicity and lower cost to that of traditional arrangements. The choice of cremation as an option to casketed burial is increasing and often includes disposition of the cremains at a time privately convenient to the deceased's family members. - The deceased is of a distinct celebrity status, and holding public ceremony would result in too many guests who are not acquainted with the deceased to participate. On the other hand, if a state funeral is offered and accepted by the deceased's immediate family, a public funeral would ensue. A recent example of this is the death of celebrity Steve Irwin, in which his family was offered a state funeral but refused. They held a private ceremony for Irwin on 9 September 2006. In some cases (particularly the latter), the family may schedule a public memorial service at a later time. ## Memorial services The memorial service is a service given for the deceased without the body present. This may take place after an earth burial, donation of the body to an institution such as a school, cremation (sometimes the cremations are present), entombment, or burial at sea. Typically these services take place at the funeral home and may include prayers, poems, or songs to remember the deceased. Pictures of the deceased are usually placed at the altar where the body would normally be to pay respects by. ## Other types of funerals ### New Orleans Jazz Funeral A unique funeral tradition in the United States occurs in New Orleans, Louisiana. The unique tradition arises from African spiritual practices, French martial musical traditions and uniquely African-American cultural influences. A typical jazz funeral begins with a march by the family, friends, and a jazz band from the home, funeral home or church to the cemetery. Throughout the march, the band plays very somber dirges. Once the final ceremony has taken place, the march proceeds from the cemetery to a gathering place, and the solemn music is replaced by loud, upbeat, raucous music and dancing where onlookers join in to celebrate the life of the deceased. This is the origin of the New Orleans dance known as the "second line" where celebrants do a dance-march, frequently while raising the hats and umbrellas brought along as protection from intense New Orleans weather and waving handkerchiefs above the head that are no longer being used to wipe away tears. ### “Green” funeral Those with concerns about the effects on the environment of traditional burial or cremation may choose to be buried in a fashion more suited to their beliefs. They may choose to be buried in a coffin made of cardboard or other easily-biodegradable materials. Further, they may choose their final resting place to be in a park or woodland, known as an eco-cemetery, and may have a tree planted over their grave as a contribution to the environment and a remembrance. ### Internet visitation/funeral A Funeral Home in North Syracuse, New York was the first funeral home to offer and broadcast a visitation and funeral "live" on the Internet. A Funeral Director at the Home said "It's not new technology, just a new application." The use of a web-camera allows relatives who could not otherwise attend services to do so from any computer. Family members and friends separated by distance, weather or circumstance can now become part of the support network by being connected electronically to the ceremonies. # Funerals in East Asia In most East Asian, South Asian and many Southeast Asian cultures, the wearing of white is symbolic of death. In these societies, white or off-white robes are traditionally worn to symbolize that someone has died and can be seen worn among relatives of the deceased during a funeral ceremony. In Chinese culture, red is strictly forbidden as it is a traditionally symbolic color of happiness. Contemporary Western influence however has meant that dark-colored or black attire is now often also acceptable for mourners to wear (particularly for those outside the family). In such cases, mourners wearing dark colors at times may also wear a white or off-white armband or white robe. A traditional Chinese gift to the attendees upon entering is a white envelope, usually enclosing a small sum of money (in odd numbers, usually one dollar), a sweet and a handkerchief, each with symbolic meaning. Chinese custom also dictates that the said sum of money should not be brought home. The sweet should be consumed the day of and anything given during the funeral must not be brought home. The repetition of 3 is common where people at the funeral may brush their hair three times or spit three times before leaving the funeral to ward off bad luck. This custom is also found in other East Asian and Southeast Asian cultures. Most Japanese funerals are conducted with Buddhist rites. Many feature a ritual that bestows a new name on the deceased; funerary names typically use obsolete or archaic kanji and words, to avoid the likelihood of the name being used in ordinary speech or writing. The new names are typically chosen by a Buddhist priest, after consulting the family of the deceased. Most Japanese are cremated. # African funerals The custom of burying the dead in the floor of dwelling-houses has been to some degree prevalent on the Gold Coast of Africa. The ceremony is purely animist, and apparently without any set ritual. The main exception is that the females of the family of the deceased and their friends may undergo mournful lamentations. In some instances they work their feelings up to an ostentatious, frenzy-like degree of sorrow. The revelry may be heightened by the use of alcohol, of which drummers, flute-players, bards, and singing men may partake. The funeral may last for as much as a week. Another custom, a kind of memorial, frequently takes place seven years after the person's death. These funerals and especially the memorials may be extremely expensive for the family in question. Cattle, sheep, goats, and poultry, may be offered in remembrance and then consumed in festivities. Some funerals in Ghana are held with the deceased put in elaborate "fantasy coffins" colored and shaped after a certain object, such as a fish, crab, boat, and even an airplane. # Ancient funeral rites The most simple and natural kind of funeral monuments, and therefore the most ancient and universal, consist in a mound of earth, or a heap of stones, raised over the body or ashes of the departed: of such monuments mention is made in the Book of Joshua, and in Homer and Virgil. The place of burial amongst the Jews was never particularly determined. Ancient Jews had burial-places upon the highways, in gardens, and upon mountains. In the Hebrew Bible (known as the Christian Old Testament), Abraham was buried with Sarah, his wife, in the cave in Machpelah, the field he bought from Ephron the Hittite; David, king of Israel, and the other kings after him (including Uzziah of Judah) "rested with ancestors" in the burial field that pertained to the kings. The primitive Greeks were buried in places prepared for that purpose in their own houses; but later they established burial grounds in desert islands, and outside the walls of towns, by that means securing them from disturbance, and themselves from the liability of catching infection from those who had died of contagious disorders. ## Funerals in ancient Rome In ancient Rome, the eldest surviving male of the household, the pater familias, was summoned to the death-bed, where he attempted to catch and inhale the last breath of the decedent. Funerals of the socially prominent were usually undertaken by professional undertakers called libitinarii. No direct description has been passed down of Roman funeral rites. These rites usually included a public procession to the tomb or pyre where the body was to be cremated. The most noteworthy thing about this procession was that the survivors bore masks bearing the images of the family's deceased ancestors. The right to carry the masks in public was eventually restricted to families prominent enough to have held curule magistracies. Mimes, dancers, and musicians hired by the undertakers, as well as professional female mourners, took part in these processions. Less well to do Romans could join benevolent funerary societies (collegia funeraticia) who undertook these rites on their behalf. Nine days after the disposal of the body, by burial or cremation, a feast was given (cena novendialis) and a libation poured over the grave or the ashes. Since most Romans were cremated, the ashes were typically collected in an urn and placed in a niche in a collective tomb called a columbarium (literally, "dovecote"). During this nine day period, the house was considered to be tainted, funesta, and was hung with yew or cypress branches to warn by passers. At the end of the period, the house was swept in an attempt to purge it of the dead person's ghost. Several Roman holidays commemorated a family's dead ancestors, including the Parentalia, held February 13 through 21, to honor the family's ancestors; and the Lemuria, held on May 9, 11, and 13, in which ghosts (larvæ) were feared to be active, and the pater familias sought to appease them with offerings of beans. The Romans prohibited burning or burying in the city, both from a sacred and civil consideration, so that the priests might not be contaminated by touching a dead body, and so that houses would not be endangered by funeral fires. Restrictions on the length, ostentation, expense of and behaviour during funerals and mourning were gradually placed by a variety of law-givers. Often the pomp and length of rites could be politically or socially motivated to advertise or aggrandise a particular kin group in Roman society. This was seen as deleterious to society and conditions for grieving were set - for instance, under some laws, women were prohibited from loud wailing or lacerating their faces and limits were introduced for expenditure on tombs and burial clothes. The Romans commonly built tombs for themselves during their lifetime. Hence these words frequently occur in ancient inscriptions, V.F. Vivus Facit, V.S.P. Vivus Sibi Posuit. The tombs of the rich were usually constructed of marble, the ground enclosed with walls, and planted round with trees. But common sepulchres were usually built below ground, and called hypogea. There were niches cut out of the walls, in which the urns were placed; these, from their resemblance to the niche of a pigeon-house, were called columbaria. ## Funerals in Scotland An old funeral rite from the Scottish Highlands is to bury the deceased with a wooden plate resting on his chest. In the plate were placed a small amount of earth and salt, to represent the future of the deceased. The earth hinted that the body would decay and become one with the earth, while the salt represented the soul, which does not decay. This rite was known as "earth laid upon a corpse". # Mutes and professional mourners From about 1600 to 1914, there were two professions in Europe now almost totally forgotten. The mute is depicted in art quite frequently but in literature is probably best known from Dickens' "Oliver Twist". Oliver is working for Sowerberry's when this conversation takes place: "There's an expression of melancholy in his face, my dear ... which is very interesting. He would make a delightful mute, my love". The main purpose of a funeral mute was to stand around at funerals with a sad, pathetic face. The professional mourner, generally a woman, would shriek and wail (often while clawing her face and tearing at her clothing), to encourage others to weep. These people are mentioned in ancient Greek plays, and were employed throughout Europe, but the practice largely died out in the nineteenth century. They continue to exist in Africa and the Middle East. The 2003 award-winning Philippine comedy Crying Ladies revolves around the lives of three women who are part-time professional mourners for the Chinese-Filipino community in Manila's Chinatown. According to the film, the Chinese use professional mourners to help expedite the entry of a deceased loved one's soul into heaven by giving the impression that he or she was a good and loving person, well-loved by many. # Funerals for heroes Viking chieftains were placed in ships after their death, together with tools and weapons. The ships were then set on a course out to sea and set ablaze. This is still re-enacted as part of festivals in the north of Europe, particularly at Up Helly-Aa and the Delamont Viking Festival. Military heroes such as Nelson, Wellington and Sir Winston Churchill had their coffins paraded through the city of London, placed on gun carriages. The guns were originally pulled by horses, but are now pulled by sailors. This is called a State Funeral. # Final disposition of the dead Some cultures place the dead in tombs of various sorts, either individually, or in specially designated tracts of land that house tombs. Burial in a graveyard is one common form of tomb. In some places, burials are impractical because the ground water is too high; therefore tombs are placed above ground, as was the case in New Orleans, Louisiana. Elsewhere, a separate building for a tomb is usually reserved for the socially prominent and wealthy. Especially grand above-ground tombs are called mausoleums. Other buildings used as tombs include the crypts in churches; burial in these places is again usually a privilege given to the socially prominent dead. In more recent times, however, this has often been forbidden by hygiene laws. Burial was not always permanent. In some areas, burial grounds needed to be re-used because of limited space. In these areas, once the dead have decomposed to skeletons, the bones are removed; after their removal they can be placed in an ossuary. "Burial at sea" means the deliberate disposal of a corpse into the ocean, wrapped and tied with weights to make sure it sinks. It is a common practice in navies and sea-faring nations; in the Church of England, special forms of funeral service were added to the Book of Common Prayer to cover it. Science fiction writers have frequently analogized with "Burial in space". Cremation, also, is an old custom; it was the usual mode of disposing of a corpse in ancient Rome (along with graves covered with heaped mounds, also found in Greece, particularly at the Karameikos graveyard in Monastiraki). Vikings were occasionally cremated in their longships, and afterwards the location of the site was marked with standing stones (see Viking funeral). In recent years, despite the objections of some religious groups, cremation has become more and more widely used. Orthodox Judaism and the Eastern Orthodox Church forbid cremation, as do most Muslims. Orthodox Judaism forbids cremation according to Jewish law (Halakha) believing that the soul of a cremated person cannot find its final repose. The Roman Catholic Church forbade it for many years, but since 1963 the church has allowed it so long as it is not done to express disbelief in bodily resurrection. The church specifies that cremated remains are either buried or entombed. They do not allow cremated remains to be scattered or kept at home. Many Catholic cemeteries now have columbarium niches for cremated remains, or specific sections for those remains. Some denominations of Protestantism allow cremation, the more conservative denominations generally do not. Hindus consider the funeral as the final "samskar" or ritual of life. Cremation is generally mandatory for all Hindus, except for saints and children under the age of 5 years. Cremation is seen as the only way in which all the five elements of fire, water, earth, air and space would be satisfied by returning the body to these elements as after cremation the ashes are poured into the sacred river Ganges or into the sea. After death the body of the deceased is placed on the ground with the head of the deceased pointing towards south which is considered the direction of the dead. The body is anointed with sacred items such as sandalwood paste and holy ashes, tulsi (basil) leaves and water from the river Ganges. The eldest son would whisper "Om namah shivay" or "Om namo bhagavate vasudevaya" near the ear of the deceased. An oil lamp is lit besides the deceased and chapters from the holy Bhagavad Gita or Garud Purana are recited. Traditionally the body has to be cremated within 24 hours after death, as keeping the body longer is considered to lead to impurity and hinder the passage of the dead to afterlife. Hence before cremation as the body lies in state, minimal physical contact with the body is observed. A priest is called in to lead the formal religious rituals, after which the body is taken to the cremation ground, where the eldest son normally lights the funeral pyre, this act is considered to be the most important duty of a son as it is believed that he leads his parents from this world into moksha. Immediately after the cremation, the family members of the deceased all have to take a purifying bath and observe a 12-day mourning period. This mourning period ends on the morning of the thirteenth day on which a Shraddh ceremony is conducted in which offerings are given to ancestors and other gods in order to grant liberation or moksha to the deceased. Recently a new method of disposing of the body, called promession or an Ecological funeral, has been patented by a Swedish company. Its main purpose is to return the body to soil quickly while minimizing pollution and resource consumption. Rarer forms of disposal of the dead include excarnation, where the corpse is exposed to the elements. This was done by some groups of Native Americans; it is still practiced by Zoroastrians in Bombay, where the Towers of Silence/Daxmas allow vultures and other carrion eating birds to dispose of the corpses. Zoroastrianism believes that fire is sacred and should not be defiled by cremating a human body. It is also practiced by some Tibetan Buddhists and is sometimes called Sky burial. Cannibalism is also practiced post-mortem in some countries. The practice has been linked to the spread of a prion disease called kuru. Mummification is the drying of bodies to preserve them. The most famous practitioners of mummification were ancient Egyptians: many nobles and high-ranked bureaucrats of the old Egyptian kingdom had their corpses embalmed and stored in luxurious sarcophagi inside their funeral mausoleum or, in the cases of some Pharaohs, a pyramid. # Control by the decedent of the details of the funeral In law in the United States, the deceased have little say in the manner in which their funerals can be conducted. The law generally holds that the funeral rituals are for the benefit of the survivors, rather than to express the personal whims and tastes of the deceased. The decedent may, in most U.S. jurisdictions, provide instructions as to his funeral by means of a Last Will and Testament. These instructions can be given some legal effect if bequests are made contingent on the heirs carrying them out, with alternative gifts if they are not followed. This assumes, of course, that the decedent has enough of an estate to make the heirs pause before doing something that will invoke the alternate bequest. To be effective, the will must be easily available, and some notion of what it provides must be known to the decedent's survivors. # Anatomical gifts Another way of avoiding some of the rituals and costs of a traditional funeral is for the decedent to donate some or all of her or his body to a medical school or similar institution for the purpose of instruction in anatomy, or for similar purposes. Students of medicine and osteopathic medicine frequently study anatomy from donated cadavers; they are also useful in forensic research. Making an anatomical gift is a separate transaction from being an organ donor, in which any useful organs are removed from the unembalmed cadaver for medical transplant. Under a Uniform Act in force in most jurisdictions of the United States, being an organ donor is a simple process that can often be accomplished when a driver's license is renewed. There are some medical conditions, such as amputations, or various surgeries, that can make the cadaver unsuitable for these purposes. Conversely, the bodies of people who had certain medical conditions are useful for research into those conditions. All US medical schools rely on the generosity of "anatomical donors" for the teaching of anatomy. Typically the remains are cremated once the students have completed their anatomy classes, and many medical schools now hold a memorial service at that time as well.	Funeral # Overview A funeral is a ceremony marking a person's death. Funerary customs comprise the complex of beliefs and practices used by a culture to remember the dead, from the funeral itself, to various monuments, prayers, and rituals undertaken in their honor. These customs vary widely between cultures, and between religious affiliations within cultures. In some cultures the dead are venerated; this is commonly called ancestor worship. The word funeral comes from the Latin funus, which had a variety of meanings, including the corpse and the funerary rites themselves. Funeral rites are as old as the human race itself, as well as other hominids.[citation needed] For example, in the Shanidar cave in Iraq, Neanderthal skeletons have been discovered with a characteristic layer of pollen, which suggests that Neanderthals buried the dead with gifts of flowers. This has been interpreted as suggesting that Neanderthals believed in an afterlife, and in any case were aware of their own mortality and were capable of mourning. # Religious funerals ## Jewish funerals ## Buddhist funerals ## Catholic Christian funerals ## Hindu funerals ## Islamic funerals ## Sikh funerals In Sikhism death is considered a natural process. An event that has absolute certainty and only happens as a direct result of God's Will or Hukam. To a Sikh, birth and death are closely associated, because they are both part of the cycle of human life of "coming and going" ( ਆਵਣੁ ਜਾਣਾ , Aana Jaana) which is seen as transient stage towards Liberation ( ਮੋਖੁ ਦੁਆਰੁ , Mokh Du-aar), complete unity with God. Sikhs thus believe in reincarnation. However, by contrast, the soul itself is not subject to the cycle of birth and death.[citation needed] Death is only the progression of the soul on its journey from God, through the created universe and back to God again. In life, a Sikh always tries to constantly remember death so that he or she may be sufficiently prayerful, detached and righteous to break the cycle of birth and death and return to God. The public display of grief at the funeral or Antam Sanskar as it is called in the Sikh culture, such as wailing or crying out loud is discouraged and should be kept to a minimum. Cremation is the preferred method of disposal, although if this is not possible any other methods such as burial or submergence at sea are acceptable. Worship of the dead with gravestones, etc. is discouraged, because the body is considered to be only the shell and the person's soul is their real essence. On the day of the cremation, the body is taken to the Gurdwara or home where hymns (Shabads) from the Guru Granth Sahib, the Sikh Scriptures are recited by the congregation, which induce feeling of consolation and courage. Kirtan may also be performed by Ragis while the relatives of the deceased recite "Waheguru" sitting near the coffin. This service normally takes from 30 to 60 minutes. At the conclusion of the service, an Ardas is said before the coffin is taken to the cremation site. At the point of cremation, a few more Shabads may be sung and final speeches are made about the deceased person. Then the Kirtan Sohila, night time prayer is recited and finally Ardas called the "Antim Ardas" ("Final Prayer") is offered. The eldest son or a close relative generally starts the cremation process – light the fire or press the button for the burning to begin. This service usually lasts about 30 to 60 minutes. The ashes are later collected and disposed by immersing them in the nearest river. Sikhs do not erect monuments over the remains of the dead.[citation needed] After the cremation ceremony, there may be another service at the Gurdwara, the Sikh place of worship, call the Sahaj Paath Bhog Ceremony but this is optional. # Funerals in Japan # Funerals in contemporary North America ## Traditional funerals Within the United States and Canada, in most cultural groups and regions, the funeral rituals can be divided into three parts: visitation, funeral, and the burial service. ### Visitation At the visitation (also called a "viewing" or "wake") the body of the deceased person (or decedent) is placed on display in the casket (also called a coffin, however almost all body containers are caskets). The viewing often takes place on one or two evenings before the funeral. The body is traditionally dressed in the decedent's best clothes. In recent times there has been more variation in what the decedent is dressed in - some people choose to be dressed in clothing more reflective of how they dressed in life. The body will often be adorned with the usual jewelry, including a watch. The jewelry and watch could be taken off and given to the family of the deceased, or remain in the casket after burial, but it most likely will be removed before cremation. The body may or may not be embalmed, depending upon such factors as the amount of time since the death has occurred, religious practices, or requirements of the place of burial. The only prescribed aspects[citation needed] of this gathering are that frequently the attendees sign a book kept by the deceased's survivors to record who attended and that the attendees are expected to view the deceased's body in the coffin. In addition, a family may choose to display photographs taken of the deceased person during his/her life (often, formal portraits with other family members and candid pictures to show "happy times"), prized possessions and other items representing his/her hobbies and/or accomplishments. A more recent trend is to create a DVD with pictures and video of the deceased, accompanied by music, and play this DVD continuously during the visitation. The viewing is either "open casket", in which the embalmed body of the deceased has been clothed and treated with cosmetics for display; or "closed casket", in which the coffin is closed. The coffin may be closed if the body was too badly damaged because of an accident or fire or other trauma, deformed from illness or if someone in the group is emotionally unable to cope with viewing the corpse. During an open casket. However, this step is foreign to Judaism; Jewish funerals are held soon after death, and the corpse is never displayed. As well, Jewish law[citation needed] forbids anyone to embalm the body of the deceased. Traditionally flowers (and music) are not sent to a grieving Jewish family as it is a reminder of the life that is now lost.(See also Jewish bereavement.) The decedent's closest friends and relatives who are unable to attend frequently send flowers to the viewing, with the exception of a Jewish Funeral [1], where flowers would not be appropriate (and donations are given to a charity instead). The viewing typically takes place at a funeral home, which is equipped with gathering rooms where the viewing can be conducted, although the viewing may also take place at a church. In earlier history, it was common practice in some of the states in the southeastern United States that the body was taken to the decedent’s home or that of a relative for viewing. The viewing may end with a prayer service; in the Catholic funeral, this may include a rosary.[citation needed] A visitation is often held the evening before the day of the funeral. However, when the deceased person is elderly the visitation may be held immediately preceding the funeral. This allows elderly friends of the deceased a chance to view the body and attend the funeral in one trip, since it may be difficult for them to arrange travel; this step may also be taken if the deceased has few survivors or the survivors want a funeral with only a small number guests. A traditional Fire Department funeral consists of two raised aerial ladders.[citation needed] The firefighter(s) travel under the aerials on their ride on the fire apparatus to the cemetery. ### Funeral A memorial service, often called a funeral and often officiated by clergy from the decedent's or bereaved's church or religion. A funeral may take place at either a funeral home or church. A funeral is held according to the family's choosing which may be a few days after the time of death, allowing family members to attend the service. The deceased is usually transported from the funeral home to a church in a hearse, a specialized vehicle designed to carry casketed remains. The deceased is often transported in a procession, with the hearse, funeral service vehicles, and private automobiles traveling in a procession to the church or other location where the services will be held. In a number of jurisdictions, special laws cover funeral processions - such as requiring other vehicles to give right-of-way to a funeral procession. Funeral service vehicles may be equipped with light bars and special flashers to increase their visibility on the roads. After the funeral service, if the deceased is to be buried the funeral procession will proceed to a cemetery if not already there. If the deceased is to be cremated the funeral procession may then proceed to the crematory. Funeral services include prayers; readings from the Bible or other sacred texts; hymns (sung either by the attendees or a hired vocalist); and words of comfort by the clergy. Frequently, a relative or close friend will be asked to give a eulogy, which details happy memories and accomplishments; often commenting on the deceased's flaws, especially at length, is considered impolite. Sometimes the delivering of the eulogy is done by the clergy. Clergy are often asked to deliver eulogies for people they have never met. Church bells may also be tolled both before and after the service. Tradition[citation needed] also allows the attendees of the memorial service to have one last opportunity to view the decedent's body and say good-bye; the immediate family (siblings (and their spouses); followed by the decedent's spouse, parents and children) are always the very last to view their loved one before the coffin is closed. This opportunity can take place immediately before the service begins, or at the very end of the service. During the funeral and at the burial service, the casket may be covered with a large arrangement of flowers, called a casket spray. If the decedent served in a branch of the Armed forces, the casket may be covered with a national flag; however nothing should cover the national flag according to Title 4, United States Code, Chapter 1, Paragraph 8i. Funeral customs vary from country to country. In the United States, any type of noise other than quiet whispering or mourning is considered disrespectful. Note: In some religious denominations, for example, Roman Catholic and Anglican, eulogies are prohibited or discouraged during this service, in order to preserve respect for traditions. Also, for these religions, the coffin is traditionally closed at the end of the wake and is not re-opened for the funeral service. ### Burial service A burial service, conducted at the side of the grave, tomb, mausoleum or crematorium, at which the body of the decedent is buried or cremated at the conclusion. Sometimes, the burial service will immediately follow the funeral, in which case a funeral procession travels from the site of the memorial service to the burial site. Other times, the burial service takes place at a later time, when the final resting place is ready. If the decedent served in a branch of the Armed forces, military rites are often accorded at the burial service. In many religious traditions, pallbearers, usually males who are close, but not immediate relatives (such as cousins, nephews or grandchildren) or friends of the decedent, will carry the casket from the chapel (of a funeral home or church) to the hearse, and from the hearse to the site of the burial service. The pallbearers often sit in a special reserved section during the memorial service. According to most religions, coffins are kept closed during the burial ceremony. In Eastern Orthodox funerals, the coffins are reopened just before burial to allow loved ones to look at the deceased one last time and give their final farewells. The morticians will typically ensure that all jewelry, including wristwatch, that were displayed at the wake are in the casket before it is buried or entombed. It would be unseemly to have the decedent's heirs squabbling over a Rolex or an engagement ring. Custom requires that everything goes into the ground. There is an exception, in the case of cremation. Such items tend to melt or suffer damage, so they are usually removed before the body goes into the furnace. Pacemakers are removed prior to cremation - if they were left in they could possibly explode and damage the crematorium. ### Luncheon In many traditions, a meal or other gathering often follows the burial service. This gathering may be held at the decedent's church or another off-site location. Some funeral homes have large spaces set aside to provide funeral dinners.[citation needed] ### Etiquette Generally speaking, the number of people who are considered obliged to attend each of these three rituals by etiquette decreases at each step: - Distant relatives and acquaintances may be called upon to attend the visitation. - The decedent's closer relatives and local friends attend the funeral or memorial service, and subsequent burial (if it is held immediately after the memorial service). - If the burial is on the day of the funeral, only the decedent's closest relatives and friends attend the burial service (although if the burial service immediately follows the funeral, all attendees of the memorial service are asked to attend). Traditionally etiquette dictated[citation needed] that the bereaved and other attendees at a funeral wear semi-formal clothing—such as a suit and tie for men or a dress for women. The most traditional and respectful color is solid black (with a matching solid black tie for men) preferably without any underlying pinstripes or patterns in the weave. But failing that charcoal gray or dark navy blue may be worn. Wearing short skirts, low-cut tops, t-shirts with advertising slogans or suggestive images, or, at Western funerals, a large amount of white (other than a button-down shirt or blouse, or a military uniform) is often seen as disrespectful.[citation needed] Women who are grieving the death of their husband or a close partner sometimes wear a veil to conceal the face, although the veil is not common now. Increasingly, the deceased have requested before their death that the attendees of their funeral should wear something of their favorite colour or wear something specific (namely a football shirt). They do this as the black did not reflect their outgoing personality. ## Private services On occasion, the family of the deceased may wish to have only a very small service, with just the deceased's closest family members and friends attending. This type of ceremony means it is closed to the public. One may only go to the funeral if one is invited. In this case, a private funeral service is conducted. Reasons vary but often include the following: - The deceased was an infant (possibly, they may have been stillborn) or very aged, and therefore has few surviving family members or friends. - The deceased may be a crime victim or a convicted criminal who was serving a prison sentence. In this case, the service is made private either to avoid unwanted media coverage (especially with a crime victim); or to avoid unwanted intrusion (especially if the deceased was convicted of murder or sexual assault). - The family does not feel able to endure a traditional service (due to emotional shock) or simply wants a quiet, simple funeral with only the most important people of the deceased's life in attendance. - The family and/or the deceased, as more frequently preplanned, prefer simplicity and lower cost to that of traditional arrangements. The choice of cremation as an option to casketed burial is increasing and often includes disposition of the cremains at a time privately convenient to the deceased's family members. - The deceased is of a distinct celebrity status, and holding public ceremony would result in too many guests who are not acquainted with the deceased to participate. On the other hand, if a state funeral is offered and accepted by the deceased's immediate family, a public funeral would ensue. A recent example of this is the death of celebrity Steve Irwin, in which his family was offered a state funeral but refused. They held a private ceremony for Irwin on 9 September 2006. In some cases (particularly the latter), the family may schedule a public memorial service at a later time. ## Memorial services The memorial service is a service given for the deceased without the body present. This may take place after an earth burial, donation of the body to an institution such as a school, cremation (sometimes the cremations are present), entombment, or burial at sea. Typically these services take place at the funeral home and may include prayers, poems, or songs to remember the deceased. Pictures of the deceased are usually placed at the altar where the body would normally be to pay respects by. ## Other types of funerals ### New Orleans Jazz Funeral A unique funeral tradition in the United States occurs in New Orleans, Louisiana. The unique tradition arises from African spiritual practices, French martial musical traditions and uniquely African-American cultural influences. A typical jazz funeral begins with a march by the family, friends, and a jazz band from the home, funeral home or church to the cemetery. Throughout the march, the band plays very somber dirges. Once the final ceremony has taken place, the march proceeds from the cemetery to a gathering place, and the solemn music is replaced by loud, upbeat, raucous music and dancing where onlookers join in to celebrate the life of the deceased. This is the origin of the New Orleans dance known as the "second line" where celebrants do a dance-march, frequently while raising the hats and umbrellas brought along as protection from intense New Orleans weather and waving handkerchiefs above the head that are no longer being used to wipe away tears. ### “Green” funeral Those with concerns about the effects on the environment of traditional burial or cremation may choose to be buried in a fashion more suited to their beliefs. They may choose to be buried in a coffin made of cardboard or other easily-biodegradable materials. Further, they may choose their final resting place to be in a park or woodland, known as an eco-cemetery, and may have a tree planted over their grave as a contribution to the environment and a remembrance. ### Internet visitation/funeral A Funeral Home in North Syracuse, New York was the first funeral home to offer and broadcast a visitation and funeral "live" on the Internet. A Funeral Director at the Home said "It's not new technology, just a new application." The use of a web-camera allows relatives who could not otherwise attend services to do so from any computer. Family members and friends separated by distance, weather or circumstance can now become part of the support network by being connected electronically to the ceremonies.[citation needed] # Funerals in East Asia In most East Asian, South Asian and many Southeast Asian cultures, the wearing of white is symbolic of death. In these societies, white or off-white robes are traditionally worn to symbolize that someone has died and can be seen worn among relatives of the deceased during a funeral ceremony. In Chinese culture, red is strictly forbidden as it is a traditionally symbolic color of happiness. Contemporary Western influence however has meant that dark-colored or black attire is now often also acceptable for mourners to wear (particularly for those outside the family). In such cases, mourners wearing dark colors at times may also wear a white or off-white armband or white robe. A traditional Chinese gift to the attendees upon entering is a white envelope, usually enclosing a small sum of money (in odd numbers, usually one dollar), a sweet and a handkerchief, each with symbolic meaning. Chinese custom also dictates that the said sum of money should not be brought home. The sweet should be consumed the day of and anything given during the funeral must not be brought home. The repetition of 3 is common where people at the funeral may brush their hair three times or spit three times before leaving the funeral to ward off bad luck. This custom is also found in other East Asian and Southeast Asian cultures.[citation needed] Most Japanese funerals are conducted with Buddhist rites. Many feature a ritual that bestows a new name on the deceased; funerary names typically use obsolete or archaic kanji and words, to avoid the likelihood of the name being used in ordinary speech or writing. The new names are typically chosen by a Buddhist priest, after consulting the family of the deceased. Most Japanese are cremated. # African funerals The custom of burying the dead in the floor of dwelling-houses has been to some degree prevalent on the Gold Coast of Africa. The ceremony is purely animist, and apparently without any set ritual. The main exception is that the females of the family of the deceased and their friends may undergo mournful lamentations. In some instances they work their feelings up to an ostentatious, frenzy-like degree of sorrow. The revelry may be heightened by the use of alcohol, of which drummers, flute-players, bards, and singing men may partake. The funeral may last for as much as a week. Another custom, a kind of memorial, frequently takes place seven years after the person's death. These funerals and especially the memorials may be extremely expensive for the family in question. Cattle, sheep, goats, and poultry, may be offered in remembrance and then consumed in festivities. Some funerals in Ghana are held with the deceased put in elaborate "fantasy coffins" colored and shaped after a certain object, such as a fish, crab, boat, and even an airplane.[1] # Ancient funeral rites The most simple and natural kind of funeral monuments, and therefore the most ancient and universal, consist in a mound of earth, or a heap of stones, raised over the body or ashes of the departed: of such monuments mention is made in the Book of Joshua, and in Homer and Virgil. The place of burial amongst the Jews was never particularly determined. Ancient Jews had burial-places upon the highways, in gardens, and upon mountains. In the Hebrew Bible (known as the Christian Old Testament), Abraham was buried with Sarah, his wife, in the cave in Machpelah, the field he bought from Ephron the Hittite; David, king of Israel, and the other kings after him (including Uzziah of Judah) "rested with [their] ancestors" in the burial field that pertained to the kings. The primitive Greeks were buried in places prepared for that purpose in their own houses; but later they established burial grounds in desert islands, and outside the walls of towns, by that means securing them from disturbance, and themselves from the liability of catching infection from those who had died of contagious disorders. ## Funerals in ancient Rome In ancient Rome, the eldest surviving male of the household, the pater familias, was summoned to the death-bed, where he attempted to catch and inhale the last breath of the decedent. Funerals of the socially prominent were usually undertaken by professional undertakers called libitinarii. No direct description has been passed down of Roman funeral rites. These rites usually included a public procession to the tomb or pyre where the body was to be cremated. The most noteworthy thing about this procession was that the survivors bore masks bearing the images of the family's deceased ancestors. The right to carry the masks in public was eventually restricted to families prominent enough to have held curule magistracies. Mimes, dancers, and musicians hired by the undertakers, as well as professional female mourners, took part in these processions. Less well to do Romans could join benevolent funerary societies (collegia funeraticia) who undertook these rites on their behalf. Nine days after the disposal of the body, by burial or cremation, a feast was given (cena novendialis) and a libation poured over the grave or the ashes. Since most Romans were cremated, the ashes were typically collected in an urn and placed in a niche in a collective tomb called a columbarium (literally, "dovecote"). During this nine day period, the house was considered to be tainted, funesta, and was hung with yew or cypress branches to warn by passers. At the end of the period, the house was swept in an attempt to purge it of the dead person's ghost. Several Roman holidays commemorated a family's dead ancestors, including the Parentalia, held February 13 through 21, to honor the family's ancestors; and the Lemuria, held on May 9, 11, and 13, in which ghosts (larvæ) were feared to be active, and the pater familias sought to appease them with offerings of beans.[citation needed] The Romans prohibited burning or burying in the city, both from a sacred and civil consideration, so that the priests might not be contaminated by touching a dead body, and so that houses would not be endangered by funeral fires. Restrictions on the length, ostentation, expense of and behaviour during funerals and mourning were gradually placed by a variety of law-givers. Often the pomp and length of rites could be politically or socially motivated to advertise or aggrandise a particular kin group in Roman society. This was seen as deleterious to society and conditions for grieving were set - for instance, under some laws, women were prohibited from loud wailing or lacerating their faces and limits were introduced for expenditure on tombs and burial clothes. The Romans commonly built tombs for themselves during their lifetime. Hence these words frequently occur in ancient inscriptions, V.F. Vivus Facit, V.S.P. Vivus Sibi Posuit. The tombs of the rich were usually constructed of marble, the ground enclosed with walls, and planted round with trees. But common sepulchres were usually built below ground, and called hypogea. There were niches cut out of the walls, in which the urns were placed; these, from their resemblance to the niche of a pigeon-house, were called columbaria. ## Funerals in Scotland An old funeral rite from the Scottish Highlands is to bury the deceased with a wooden plate resting on his chest. In the plate were placed a small amount of earth and salt, to represent the future of the deceased. The earth hinted that the body would decay and become one with the earth, while the salt represented the soul, which does not decay. This rite was known as "earth laid upon a corpse".[citation needed] # Mutes and professional mourners From about 1600 to 1914, there were two professions in Europe now almost totally forgotten. The mute is depicted in art quite frequently but in literature is probably best known from Dickens' "Oliver Twist". Oliver is working for Sowerberry's when this conversation takes place: "There's an expression of melancholy in his face, my dear ... which is very interesting. He would make a delightful mute, my love". The main purpose of a funeral mute was to stand around at funerals with a sad, pathetic face. The professional mourner, generally a woman, would shriek and wail (often while clawing her face and tearing at her clothing), to encourage others to weep. These people are mentioned[citation needed] in ancient Greek plays, and were employed throughout Europe, but the practice largely died out in the nineteenth century. They continue to exist in Africa and the Middle East.[citation needed] The 2003 award-winning Philippine comedy Crying Ladies revolves around the lives of three women who are part-time professional mourners for the Chinese-Filipino community in Manila's Chinatown. According to the film, the Chinese use professional mourners to help expedite the entry of a deceased loved one's soul into heaven by giving the impression that he or she was a good and loving person, well-loved by many. # Funerals for heroes Viking chieftains were placed in ships after their death, together with tools and weapons.[citation needed] The ships were then set on a course out to sea and set ablaze. This is still re-enacted as part of festivals in the north of Europe, particularly at Up Helly-Aa and the Delamont Viking Festival. Military heroes such as Nelson, Wellington and Sir Winston Churchill had their coffins paraded through the city of London, placed on gun carriages. The guns were originally pulled by horses, but are now pulled by sailors. This is called a State Funeral. # Final disposition of the dead Some cultures place the dead in tombs of various sorts, either individually, or in specially designated tracts of land that house tombs. Burial in a graveyard is one common form of tomb. In some places, burials are impractical because the ground water is too high; therefore tombs are placed above ground, as was the case in New Orleans, Louisiana. Elsewhere, a separate building for a tomb is usually reserved for the socially prominent and wealthy. Especially grand above-ground tombs are called mausoleums. Other buildings used as tombs include the crypts in churches; burial in these places is again usually a privilege given to the socially prominent dead. In more recent times, however, this has often been forbidden by hygiene laws. Burial was not always permanent. In some areas, burial grounds needed to be re-used because of limited space. In these areas, once the dead have decomposed to skeletons, the bones are removed; after their removal they can be placed in an ossuary. "Burial at sea" means the deliberate disposal of a corpse into the ocean, wrapped and tied with weights to make sure it sinks. It is a common practice in navies and sea-faring nations; in the Church of England, special forms of funeral service were added to the Book of Common Prayer to cover it. Science fiction writers have frequently analogized with "Burial in space". Cremation, also, is an old custom; it was the usual mode of disposing of a corpse in ancient Rome (along with graves covered with heaped mounds, also found in Greece, particularly at the Karameikos graveyard in Monastiraki). Vikings were occasionally cremated in their longships, and afterwards the location of the site was marked with standing stones (see Viking funeral). In recent years, despite the objections of some religious groups, cremation has become more and more widely used. Orthodox Judaism and the Eastern Orthodox Church forbid cremation, as do most Muslims. Orthodox Judaism forbids cremation according to Jewish law (Halakha) believing that the soul of a cremated person cannot find its final repose. The Roman Catholic Church forbade it for many years, but since 1963 the church has allowed it so long as it is not done to express disbelief in bodily resurrection. The church specifies that cremated remains are either buried or entombed. They do not allow cremated remains to be scattered or kept at home. Many Catholic cemeteries now have columbarium niches for cremated remains, or specific sections for those remains. Some denominations of Protestantism allow cremation, the more conservative denominations generally do not. Hindus consider the funeral as the final "samskar" or ritual of life.[citation needed] Cremation is generally mandatory for all Hindus, except for saints and children under the age of 5 years.[citation needed] Cremation is seen as the only way in which all the five elements of fire, water, earth, air and space would be satisfied by returning the body to these elements as after cremation the ashes are poured into the sacred river Ganges or into the sea. After death the body of the deceased is placed on the ground with the head of the deceased pointing towards south which is considered the direction of the dead. The body is anointed with sacred items such as sandalwood paste and holy ashes, tulsi (basil) leaves and water from the river Ganges. The eldest son would whisper "Om namah shivay" or "Om namo bhagavate vasudevaya" near the ear of the deceased.[citation needed] An oil lamp is lit besides the deceased and chapters from the holy Bhagavad Gita or Garud Purana are recited. Traditionally the body has to be cremated within 24 hours after death, as keeping the body longer is considered to lead to impurity and hinder the passage of the dead to afterlife. Hence before cremation as the body lies in state, minimal physical contact with the body is observed. A priest is called in to lead the formal religious rituals, after which the body is taken to the cremation ground, where the eldest son normally lights the funeral pyre, this act is considered to be the most important duty of a son as it is believed that he leads his parents from this world into moksha. Immediately after the cremation, the family members of the deceased all have to take a purifying bath and observe a 12-day mourning period. This mourning period ends on the morning of the thirteenth day on which a Shraddh ceremony is conducted in which offerings are given to ancestors and other gods in order to grant liberation or moksha to the deceased. Recently a new method of disposing of the body, called promession or an Ecological funeral, has been patented by a Swedish company.[citation needed] Its main purpose is to return the body to soil quickly while minimizing pollution and resource consumption. Rarer forms of disposal of the dead include excarnation, where the corpse is exposed to the elements. This was done by some groups of Native Americans; it is still practiced by Zoroastrians in Bombay, where the Towers of Silence/Daxmas allow vultures and other carrion eating birds to dispose of the corpses. Zoroastrianism believes that fire is sacred and should not be defiled by cremating a human body. It is also practiced by some Tibetan Buddhists and is sometimes called Sky burial.[citation needed] Cannibalism is also practiced post-mortem in some countries. The practice has been linked to the spread of a prion disease called kuru[2].[citation needed] Mummification is the drying of bodies to preserve them. The most famous practitioners of mummification were ancient Egyptians: many nobles and high-ranked bureaucrats of the old Egyptian kingdom had their corpses embalmed and stored in luxurious sarcophagi inside their funeral mausoleum or, in the cases of some Pharaohs, a pyramid.[citation needed] # Control by the decedent of the details of the funeral In law in the United States, the deceased have little say in the manner in which their funerals can be conducted. The law generally holds[citation needed] that the funeral rituals are for the benefit of the survivors, rather than to express the personal whims and tastes of the deceased. The decedent may, in most U.S. jurisdictions, provide instructions as to his funeral by means of a Last Will and Testament. These instructions can be given some legal effect if bequests are made contingent on the heirs carrying them out, with alternative gifts if they are not followed. This assumes, of course, that the decedent has enough of an estate to make the heirs pause before doing something that will invoke the alternate bequest. To be effective, the will must be easily available, and some notion of what it provides must be known to the decedent's survivors.[citation needed] # Anatomical gifts Another way of avoiding some of the rituals and costs of a traditional funeral is for the decedent to donate some or all of her or his body to a medical school or similar institution for the purpose of instruction in anatomy, or for similar purposes. Students of medicine and osteopathic medicine frequently study anatomy from donated cadavers; they are also useful in forensic research. Making an anatomical gift is a separate transaction from being an organ donor, in which any useful organs are removed from the unembalmed cadaver for medical transplant. Under a Uniform Act in force in most jurisdictions of the United States, being an organ donor is a simple process that can often be accomplished when a driver's license is renewed.[citation needed] There are some medical conditions, such as amputations, or various surgeries, that can make the cadaver unsuitable for these purposes. Conversely, the bodies of people who had certain medical conditions are useful for research into those conditions. All US medical schools rely on the generosity of "anatomical donors" for the teaching of anatomy. Typically the remains are cremated once the students have completed their anatomy classes, and many medical schools now hold a memorial service at that time as well.[citation needed]	https://www.wikidoc.org/index.php/Funeral
34a11c911cf34ba9ba5b1c046641bb56a54784c9	wikidoc	Mycosis	Mycosis Synonyms and keywords: Fungus and fungal infections; mycete; mycoses; fungus infections # Overview The Term mycosis (plural: mycoses) refers to conditions in which fungi pass the resistance barriers of the human or animal body and establish infections. Mycoses are common, and a variety of environmental and physiological conditions can contribute to the development of fungal diseases. Inhalation of fungal spores or localized colonization of the skin may initiate persistent infections; therefore, mycoses often start in the lungs or on the skin. # Causes People are at risk of fungal infections when they are taking strong antibiotics for a long period of time because antibiotics kill not only damaging bacteria, but healthy bacteria as well. This alters the balance of microorganisms in the mouth, vagina, intestines and other places in the body, and results in an overgrowth of fungus. Individuals with weakened immune systems are also at risk of developing fungal infections. This is the case of people with HIV/AIDS, people under steroid treatments, and people taking chemotherapy. People with diabetes also tend to develop fungal infections. Very young and very old people, also, are groups at risk. # Classification Mycoses are classified according to the tissue levels initially colonized: - Superficial mycoses - limited to the outermost layers of the skin and hair. - Cutaneous mycoses - extend deeper into the epidermis, as well as invasive hair and nail diseases. These diseases are restricted to the keratinized layers of the skin, hair, and nails. Unlike the superficial mycoses, host immune responses may be evoked, resulting in pathologic changes expressed in the deeper layers of the skin. The organisms that cause these diseases are called dermatophytes. The resulting diseases are often called ringworm (even though there is no worm involved) or tinea. Cutaneous mycoses are caused by Microsporum, Trichophyton, and Epidermophyton fungi, which together comprise 41 species. - Subcutaneous mycoses - involve the dermis, subcutaneous tissues, muscle, and fascia. These infections are chronic and can be initiated by piercing trauma to the skin, which allows the fungi to enter. These infections are difficult to treat and may require surgical interventions such as debridement. - Systemic mycoses due to primary pathogens - originate primarily in the lungs and may spread to many organ systems. Organisms that cause systemic mycoses are inherently virulent. Generally, primary pathogens that cause systemic mycoses are dimorphic. - Systemic mycoses due to opportunistic pathogens - infections of patients with immune deficiencies who would otherwise not be infected. Examples of immunocompromised conditions include AIDS, alteration of normal flora by antibiotics, immunosuppressive therapy, and metastatic cancer. Examples of opportunistic mycoses include Candidiasis, Cryptococcosis and Aspergillosis. Another example of a fungal infection is Tinea versicolor: Tinea versicolor is a fungus infection that commonly affects the skin of young people, especially the chest, back, and upper arms and legs. Tinea versicolor is caused by a fungus that lives in the skin of almost all adults. It doesn't usually affect the face. This fungus produces spots that are either lighter than the skin or a reddish-brown. There may be just a few spots or lots of spots. Tinea versicolor is caused by a fungus that lives in the skin of almost all adults. This fungus exists in two forms, one causes visible spots. Factors that can cause the fungus to become more visible include high humidity and immune or hormone abnormalities. But almost all people with this very common condition are healthy. # Treatment Antifungal drugs are used to treat mycoses. Depending on the nature of the infection, a topical or systemic agent may be used. Photochemotherapy or photopheresis is a technique used at major medical centers for the treatment of mycosis fungoides. An example of antifungal is fluconazole, or Diflucan, which is the basis of many over-the-counter antifungal treatments. Another example is amphotericin B (the A form being toxic) which is more potent. It is used in the treatment of the most severe fungal infections that show resistance to other forms of treatment and it is administered intravenously. Drugs to treat skin infections are Tolnaftate (Tinactin), an over the counter topical; Ketoconazole, especially used to treat tinea versicolor and other dermatophytes; Itraconazole; Terbinafine (Lamisil); Echinocandins (caspofungin); Griseofulvin, commonly used for infections involving the scalp and nails. Yeast infections in the vagina, caused by candida albicans, can be treated with medicated suppositories and pessaries whereas skin yeast infections are treated with medicated ointments. ## Contraindicated Medications - Dexamethasone - Prednisolone - Prednisone # Prevention Keeping the skin clean and dry, as well as maintaining good hygiene, will help prevent topical mycoses. Because fungal infections are contagious, it is important to wash after touching other people or animals. Sports clothing should also be washed after use. Wearing flip-flops when using a community swimming pool or shower will also prevent topical infections. # Related Chapters - Dermatophytosis - Pathogenic fungi - Black hairy tongue cs:Mykóza de:Mykose eu:Mikosi he:פטרת hu:Gombásodás ms:Mikosis nl:Mycose	Mycosis For patient information click here Template:DiseaseDisorder infobox Template:Search infobox Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Synonyms and keywords: Fungus and fungal infections; mycete; mycoses; fungus infections # Overview The Term mycosis (plural: mycoses) refers to conditions in which fungi pass the resistance barriers of the human or animal body and establish infections. Mycoses are common, and a variety of environmental and physiological conditions can contribute to the development of fungal diseases. Inhalation of fungal spores or localized colonization of the skin may initiate persistent infections; therefore, mycoses often start in the lungs or on the skin. # Causes People are at risk of fungal infections when they are taking strong antibiotics for a long period of time because antibiotics kill not only damaging bacteria, but healthy bacteria as well. This alters the balance of microorganisms in the mouth, vagina, intestines and other places in the body, and results in an overgrowth of fungus. Individuals with weakened immune systems are also at risk of developing fungal infections. This is the case of people with HIV/AIDS, people under steroid treatments, and people taking chemotherapy. People with diabetes also tend to develop fungal infections. Very young and very old people, also, are groups at risk. # Classification Mycoses are classified according to the tissue levels initially colonized: - Superficial mycoses - limited to the outermost layers of the skin and hair. - Cutaneous mycoses - extend deeper into the epidermis, as well as invasive hair and nail diseases. These diseases are restricted to the keratinized layers of the skin, hair, and nails. Unlike the superficial mycoses, host immune responses may be evoked, resulting in pathologic changes expressed in the deeper layers of the skin. The organisms that cause these diseases are called dermatophytes. The resulting diseases are often called ringworm (even though there is no worm involved) or tinea. Cutaneous mycoses are caused by Microsporum, Trichophyton, and Epidermophyton fungi, which together comprise 41 species. - Subcutaneous mycoses - involve the dermis, subcutaneous tissues, muscle, and fascia. These infections are chronic and can be initiated by piercing trauma to the skin, which allows the fungi to enter. These infections are difficult to treat and may require surgical interventions such as debridement. - Systemic mycoses due to primary pathogens - originate primarily in the lungs and may spread to many organ systems. Organisms that cause systemic mycoses are inherently virulent. Generally, primary pathogens that cause systemic mycoses are dimorphic. - Systemic mycoses due to opportunistic pathogens - infections of patients with immune deficiencies who would otherwise not be infected. Examples of immunocompromised conditions include AIDS, alteration of normal flora by antibiotics, immunosuppressive therapy, and metastatic cancer. Examples of opportunistic mycoses include Candidiasis, Cryptococcosis and Aspergillosis. Another example of a fungal infection is Tinea versicolor: Tinea versicolor is a fungus infection that commonly affects the skin of young people, especially the chest, back, and upper arms and legs. Tinea versicolor is caused by a fungus that lives in the skin of almost all adults. It doesn't usually affect the face. This fungus produces spots that are either lighter than the skin or a reddish-brown. There may be just a few spots or lots of spots. Tinea versicolor is caused by a fungus that lives in the skin of almost all adults. This fungus exists in two forms, one causes visible spots. Factors that can cause the fungus to become more visible include high humidity and immune or hormone abnormalities. But almost all people with this very common condition are healthy. # Treatment Antifungal drugs are used to treat mycoses. Depending on the nature of the infection, a topical or systemic agent may be used. Photochemotherapy or photopheresis is a technique used at major medical centers for the treatment of mycosis fungoides. An example of antifungal is fluconazole, or Diflucan, which is the basis of many over-the-counter antifungal treatments. Another example is amphotericin B (the A form being toxic) which is more potent. It is used in the treatment of the most severe fungal infections that show resistance to other forms of treatment and it is administered intravenously. Drugs to treat skin infections are Tolnaftate (Tinactin), an over the counter topical; Ketoconazole, especially used to treat tinea versicolor and other dermatophytes; Itraconazole; Terbinafine (Lamisil); Echinocandins (caspofungin); Griseofulvin, commonly used for infections involving the scalp and nails. Yeast infections in the vagina, caused by candida albicans, can be treated with medicated suppositories and pessaries whereas skin yeast infections are treated with medicated ointments. ## Contraindicated Medications - Dexamethasone - Prednisolone - Prednisone # Prevention Keeping the skin clean and dry, as well as maintaining good hygiene, will help prevent topical mycoses. Because fungal infections are contagious, it is important to wash after touching other people or animals. Sports clothing should also be washed after use. Wearing flip-flops when using a community swimming pool or shower will also prevent topical infections. # Related Chapters - Dermatophytosis - Pathogenic fungi - Black hairy tongue Template:Mycoses cs:Mykóza de:Mykose eu:Mikosi he:פטרת hu:Gombásodás ms:Mikosis nl:Mycose Template:WH Template:WS	https://www.wikidoc.org/index.php/Fungal_infection
9a66bf84a4ba9ab580495c26e424ace374f7f944	wikidoc	Ouabain	Ouabain # Overview Ouabain (from Somali waabaayo, "arrow poison" through French ouabaïo) also known as g-strophanthin, is a cardiac glycoside. Sometimes used in the treatment of heart conditions, it has also been used as a powerful arrow poison by some tribal peoples. # Sources Ouabain (g-strophanthin) is found in the ripe seeds of African plants Strophanthus gratus and the bark of Acokanthera ouabaio. # Function It is well understood that the classical mechanism of action of ouabain involves its binding to and inhibition of the plasma membrane Na+/K+-ATPase (sodium/potassium pump) especially at the higher concentrations attainable in vitro or with intravenous dosage. Inhibition of the sodium pump and the secondary effect on the handling of calcium ions by sodium calcium exchanger (NCX) is widely believed to underlie the original beneficial effect as an inotropic agent following intravenous use of ouabain; digoxin is a structurally related and more lipophilic cardiac glycoside that largely replaced ouabain for therapy because of its superior oral bioavailability. Digoxin continues to be used therapeutically for many of the same indications in which ouabain was used (including atrial fibrillation and congestive heart failure). In addition to the classical mechanism of action of ouabain at high concentrations, low (nanomolar and subnanomolar) concentrations of ouabain, as they were found endogenously (see below) or after oral intake, stimulate the Na-K-ATPase. This stimulatory effect does not appear to be mimicked by digoxin. Furthermore ouabain acts as a signal transducer. # Endogenous ouabain and ouabain mimics In 1991, a potent sodium pump inhibitor was isolated from the human circulation and identified as ouabain. Several additional observations led to the view that the circulating ouabain in humans was an endogenous hormone. A reinterpretation of a portion of the analytical data led to the proposal that endogenous ouabain may have been the 11 epimer, i.e., an isomer of plant ouabain. However, this possibility has been excluded by the synthesis of the 11 epimer and the demonstration that it has different chromatographic behavior from ouabain. There is compelling analytical evidence that ouabain is synthesized in the adrenal gland. A ouabain-like factor may also be made in the hypothalamus and possibly the heart where it may be stimulated by oxygen deficiency. In the latter instances, analytical data are needed to support the identity of the secreted materials. Further, secretion is not equivalent to biosynthesis; most all (most or all?) tissues sequester ouabain from the circulation. When such tissues are removed from the circulation they secrete ouabain but this phenomenon, by itself, is not proof of biosynthesis. The mode of action and significance of physiological levels of endogenous ouabain are under active investigation. In human plasma from healthy individuals, the circulating levels are normally distributed in the population and range typically from 30 - 380 pM. Significantly higher levels of endogenous ouabain that may approach or even exceed 1 nM have been observed in many patients with congestive heart failure, essential hypertension, renal failure and some cancers. It has been suggested that physiological concentrations of ouabain promote cell growth and in some manner stimulate the Na+/K+-ATPase activity while the higher levels achieved during intravenous therapy or in pathophysiological disorders may inhibit the Na+/K+-ATPase. In the years following the discovery of ouabain in the human circulation, it was found in the adrenal glands of cows and dogs. # Uses Extracts containing ouabain have long been used by Somali tribesmen and other groups to poison hunting arrows. A sufficiently concentrated ouabain dart can bring down a Hippopotamus probably as the result of respiratory and/or cardiac arrest. In France and Germany, intravenous ouabain has a long history in the treatment of heart failure, and some continue to advocate its use intravenously and per os (orally) in angina pectoris and myocardial infarction. The positive properties of ouabain regarding the prophylaxis and treatment of these two indications are documented by a clutch of studies. Ouabain isolated from plants is widely used by scientists in in vitro studies to specifically block the sodium pump (Na-K-ATPase). In many non-rodent species, low concentrations of this substance (i.e., in the subnanomolar range) may stimulate the Na-K-ATPase. The mechanism of the stimulatory effect is not understood and remains controversial. Further, the issue in rodents is more complicated because there are different isoforms of the Na-K-ATPase - some of which are very sensitive to ouabain while others are not. The parenteral absorption seems to be better than indicated by the textbooks. Recently, use of ouabain as a contraceptive has been investigated, showing that it can severely decrease the motility of spermatozoa.	Ouabain Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] # Overview Ouabain (from Somali waabaayo, "arrow poison" through French ouabaïo) also known as g-strophanthin, is a cardiac glycoside. Sometimes used in the treatment of heart conditions, it has also been used as a powerful arrow poison by some tribal peoples. # Sources Ouabain (g-strophanthin) is found in the ripe seeds of African plants Strophanthus gratus and the bark of Acokanthera ouabaio. # Function It is well understood that the classical mechanism of action of ouabain involves its binding to and inhibition of the plasma membrane Na+/K+-ATPase (sodium/potassium pump) especially at the higher concentrations attainable in vitro or with intravenous dosage. Inhibition of the sodium pump and the secondary effect on the handling of calcium ions by sodium calcium exchanger (NCX) is widely believed to underlie the original beneficial effect as an inotropic agent following intravenous use of ouabain; digoxin is a structurally related and more lipophilic cardiac glycoside that largely replaced ouabain for therapy because of its superior oral bioavailability. Digoxin continues to be used therapeutically for many of the same indications in which ouabain was used (including atrial fibrillation and congestive heart failure). In addition to the classical mechanism of action of ouabain at high concentrations, low (nanomolar and subnanomolar) concentrations of ouabain, as they were found endogenously (see below) or after oral intake, stimulate the Na-K-ATPase.[1] This stimulatory effect does not appear to be mimicked by digoxin.[2] Furthermore ouabain acts as a signal transducer.[3] # Endogenous ouabain and ouabain mimics In 1991, a potent sodium pump inhibitor was isolated from the human circulation and identified as ouabain. Several additional observations led to the view that the circulating ouabain in humans was an endogenous hormone.[4] A reinterpretation of a portion of the analytical data led to the proposal that endogenous ouabain may have been the 11 epimer, i.e., an isomer of plant ouabain.[5] However, this possibility has been excluded by the synthesis of the 11 epimer and the demonstration that it has different chromatographic behavior from ouabain. There is compelling analytical evidence that ouabain is synthesized in the adrenal gland.[6] A ouabain-like factor may also be made in the hypothalamus[7] and possibly the heart where it may be stimulated by oxygen deficiency.[8] In the latter instances, analytical data are needed to support the identity of the secreted materials. Further, secretion is not equivalent to biosynthesis; most all (most or all?) tissues sequester ouabain from the circulation. When such tissues are removed from the circulation they secrete ouabain but this phenomenon, by itself, is not proof of biosynthesis. The mode of action and significance of physiological levels of endogenous ouabain are under active investigation. In human plasma from healthy individuals, the circulating levels are normally distributed in the population and range typically from 30 - 380 pM. Significantly higher levels of endogenous ouabain that may approach or even exceed 1 nM have been observed in many patients with congestive heart failure, essential hypertension, renal failure and some cancers. It has been suggested that physiological concentrations of ouabain promote cell growth and in some manner stimulate the Na+/K+-ATPase activity while the higher levels achieved during intravenous therapy or in pathophysiological disorders may inhibit the Na+/K+-ATPase.[1] In the years following the discovery of ouabain in the human circulation, it was found in the adrenal glands of cows[9] and dogs.[10] # Uses Extracts containing ouabain have long been used by Somali tribesmen and other groups to poison hunting arrows.[11] A sufficiently concentrated ouabain dart can bring down a Hippopotamus probably as the result of respiratory and/or cardiac arrest. In France and Germany, intravenous ouabain has a long history in the treatment of heart failure, and some continue to advocate its use intravenously and per os (orally) in angina pectoris and myocardial infarction. The positive properties of ouabain regarding the prophylaxis and treatment of these two indications are documented by a clutch of studies.[12] Ouabain isolated from plants is widely used by scientists in in vitro studies to specifically block the sodium pump (Na-K-ATPase). In many non-rodent species, low concentrations of this substance (i.e., in the subnanomolar range) may stimulate the Na-K-ATPase. The mechanism of the stimulatory effect is not understood and remains controversial. Further, the issue in rodents is more complicated because there are different isoforms of the Na-K-ATPase - some of which are very sensitive to ouabain while others are not. The parenteral absorption seems to be better than indicated by the textbooks.[12] Recently, use of ouabain as a contraceptive has been investigated, showing that it can severely decrease the motility of spermatozoa.[13]	https://www.wikidoc.org/index.php/G-strophanthin
b22ebcda925f6b6a0fc523ac7a9bfd6d3a173c4b	wikidoc	GABARAP	GABARAP Gamma-aminobutyric acid receptor-associated protein is a protein that in humans is encoded by the GABARAP gene. # Function Gamma-aminobutyric acid A receptors are ligand-gated chloride channels that mediate inhibitory neurotransmission. This gene encodes GABA(A) receptor-associated protein, which is highly positively charged in its N-terminus and shares sequence similarity with light chain-3 of microtubule-associated proteins 1A and 1B. This protein clusters neurotransmitter receptors by mediating interaction with the cytoskeleton. Moreover, GABARAP has an important function in autophagosome mediated autophagy, since it is crucial for autophagosome formation and sequestration of cytosolic cargo into double-membrane vesicles, leading to subsequent degradation after fusion with lysosomes. In addition, GABARAP can mediate selective autophagy because it binds to so-called autophagic receptors (e.g. p62, NBr1), which bind and recruit specific cargo. # Interactions GABARAP has been shown to interact with TFRC, ULK1 and GABRG2.	GABARAP Gamma-aminobutyric acid receptor-associated protein is a protein that in humans is encoded by the GABARAP gene.[1] # Function Gamma-aminobutyric acid A receptors [GABA(A) receptors] are ligand-gated chloride channels that mediate inhibitory neurotransmission. This gene encodes GABA(A) receptor-associated protein, which is highly positively charged in its N-terminus and shares sequence similarity with light chain-3 of microtubule-associated proteins 1A and 1B. This protein clusters neurotransmitter receptors by mediating interaction with the cytoskeleton.[2] Moreover, GABARAP has an important function in autophagosome mediated autophagy, since it is crucial for autophagosome formation and sequestration of cytosolic cargo into double-membrane vesicles, leading to subsequent degradation after fusion with lysosomes.[3] In addition, GABARAP can mediate selective autophagy because it binds to so-called autophagic receptors (e.g. p62, NBr1), which bind and recruit specific cargo. # Interactions GABARAP has been shown to interact with TFRC,[4] ULK1[5][6] and GABRG2.[1][7][8]	https://www.wikidoc.org/index.php/GABARAP
ed046ba9ee0efb87298c8b5a5c06b6cebf4216b5	wikidoc	GADD45A	GADD45A Growth arrest and DNA-damage-inducible protein GADD45 alpha is a protein that in humans is encoded by the GADD45A gene. # Function This gene is a member of a group of genes, the GADD45 genes, whose transcript levels are increased following stressful growth arrest conditions and treatment with DNA-damaging agents (mutagens). The DNA damage-induced transcription of this gene is mediated by both p53-dependent and -independent mechanisms. The protein encoded by this gene responds to environmental stresses by mediating activation of the p38/JNK pathway via MTK1/MEKK4 kinase. # Applications The fact that expression of this gene is an indicator of DNA damage has been exploited to construct an in vitro test for mutagenicity, the GADD45a-GFP GreenScreen HC assay. This assay consists of a cell line which has been engineered so that expression of GADD45A will lead to expression of green fluorescent protein, which can easily be detected. To test a substance for mutagenicity, it is applied to these cells and fluorescence is measured. # Interactions GADD45A has been shown to interact with: - AURKA, - Cdk1, - CCNB1, - GADD45GIP1 - MAP3K4, - P21, and - PCNA.	GADD45A Growth arrest and DNA-damage-inducible protein GADD45 alpha is a protein that in humans is encoded by the GADD45A gene.[1][2][3] # Function This gene is a member of a group of genes, the GADD45 genes, whose transcript levels are increased following stressful growth arrest conditions and treatment with DNA-damaging agents (mutagens). The DNA damage-induced transcription of this gene is mediated by both p53-dependent and -independent mechanisms. The protein encoded by this gene responds to environmental stresses by mediating activation of the p38/JNK pathway via MTK1/MEKK4 kinase.[3] # Applications The fact that expression of this gene is an indicator of DNA damage has been exploited to construct an in vitro test for mutagenicity, the GADD45a-GFP GreenScreen HC assay.[4] This assay consists of a cell line which has been engineered so that expression of GADD45A will lead to expression of green fluorescent protein, which can easily be detected. To test a substance for mutagenicity, it is applied to these cells and fluorescence is measured. # Interactions GADD45A has been shown to interact with: - AURKA,[5][5] - Cdk1,[6][7][8][9] - CCNB1,[6][9] - GADD45GIP1[10] - MAP3K4,[11] - P21,[8][12] and - PCNA.[8][13][14][15][16]	https://www.wikidoc.org/index.php/GADD45A
430bc89affd38149d0c8825fb68793b18af6ccab	wikidoc	GADD45B	GADD45B Growth arrest and DNA-damage-inducible, beta, also known as GADD45B, is a protein which in humans is encoded by the GADD45B gene. # Function This gene is a member of a group of genes whose transcript levels are increased following stressful growth arrest conditions and treatment with DNA-damaging agents. The genes in this group respond to environmental stresses by mediating activation of the p38/JNK pathway. This activation is mediated via their proteins binding and activating MTK1/MEKK4 kinase, which is an upstream activator of both p38 and JNK MAPKs. The function of these genes or their protein products is involved in the regulation of growth and apoptosis. These genes are regulated by different mechanisms, but they are often coordinately expressed and can function cooperatively in inhibiting cell growth. Gadd45b is required for activity-induced DNA demethylation of specific promoters and expression of corresponding genes necessary for adult neurogenesis, including brain-derived neurotrophic factor and fibroblast growth factor. Hence GADD45B is implicated in affecting synaptic plasticity. # Interactions GADD45B has been shown to interact with: - ASK1, - GADD45GIP1, - MAP2K7 and - MAP3K4.	GADD45B Growth arrest and DNA-damage-inducible, beta, also known as GADD45B, is a protein which in humans is encoded by the GADD45B gene.[1][2][3] # Function This gene is a member of a group of genes whose transcript levels are increased following stressful growth arrest conditions and treatment with DNA-damaging agents. The genes in this group respond to environmental stresses by mediating activation of the p38/JNK pathway. This activation is mediated via their proteins binding and activating MTK1/MEKK4 kinase, which is an upstream activator of both p38 and JNK MAPKs. The function of these genes or their protein products is involved in the regulation of growth and apoptosis. These genes are regulated by different mechanisms, but they are often coordinately expressed and can function cooperatively in inhibiting cell growth.[1] Gadd45b is required for activity-induced DNA demethylation of specific promoters and expression of corresponding genes necessary for adult neurogenesis, including brain-derived neurotrophic factor and fibroblast growth factor. Hence GADD45B is implicated in affecting synaptic plasticity.[4] # Interactions GADD45B has been shown to interact with: - ASK1,[5] - GADD45GIP1,[6] - MAP2K7[5] and - MAP3K4.[3]	https://www.wikidoc.org/index.php/GADD45B
8de27e878e60e34d43218c5fb4fc10536e128595	wikidoc	GADD45G	GADD45G Growth arrest and DNA-damage-inducible protein GADD45 gamma is a protein that in humans is encoded by the GADD45G gene on chromosome 9. GADD45G is also known as CR6, DDIT2, GRP17, OIG37, and GADD45gamma. GADD45G is involved in several different processes, including sexual development, human-specific brain development, tumor suppression, and the cellular stress response. GADD45G interacts with several other proteins that are involved in DNA repair, cell cycle control, apoptosis, and senescence. Low expression of GADD45G has been associated with many types of cancer. # History GADD45G was originally cloned by Beadling under the name CR6 in 1993. In this experiment, several genes including GADD45G were noted for being induced by IL-2, and they were identified as immediate early response genes in T lymphocytes. Its role as a tumor suppressor was discovered in 1999 by Zhang. It received the name OIG37 from Nakayama due to its regulation by Oncostatin M, which was found to be able to inhibit growth. Finally, it also became known as Gadd-related protein 17 during its isolation from a cDNA library by Suzuki due to its homology with Gadd45. # Structure and function GADD45G is a member of a group of genes whose transcript levels are increased following stressful growth arrest conditions and treatment with DNA-damaging agents. The protein encoded by this gene responds to environmental stresses by mediating activation of the p38/JNK pathway via MTK1/MEKK4 kinase. GADD45G is in turn regulated upstream by NF-κB. The crystal structure of GADD45G reveals a dimer made of four parallel helices. The central region contains a highly acidic patch where it allows for interaction with cdc2, PCNA, and p21. The parallel isoform of GADD45G is the active form. This gene plays a role in cell cycle regulation. GADD45G prevents the kinase ability of the cyclin b1/Cdk1 complex in a fashion that does not break apart the complex. It plays a role in the activation of the S and G2/M checkpoints. In the male sexual development pathway, GADD45G is essential for activating SRY, leading to proper formation of the gonads and sex-determination. This could occur through GADD45G interaction with the p38 MAPK signaling pathway. Deletion of an enhancer close to the GADD45G gene is correlated to increased proliferation of neuronal cells, which could account for part of the difference in neural development between humans and other species. The deletion of the enhancer reduces the expression of the gene in the forebrain allowing for more brain growth in humans. GADD45G is involved with dental epithelial cell proliferation. GADD45G is expressed in enamel knots, where it regulates gene expression and cell growth. The gene modulates p21-mediated epithelial cell proliferation by activating the p38 MAPK pathway during the development of teeth. There is differential expression of the Xenopus homolog of GADD45G in embryonic development. It plays a large role in neural and brain development with GADD45A. GADD45G and GADD45A knockdowns are related to improper gastrulation, defective head growth, and shorter axes. GADD45G and GADD45A act redundantly to control cell growth, allow the cells to move from pluripotentcy helping cells differentiate. # Interactions GADD45G carries out its many previously stated functions with many different interactions. GADD45G was found to inhibit Cdk1 kinase activity, which would cause disruption of cell growth. It also interacts with CRIF, which causes the inhibition of Cdc2-cyclin B1 and Cdk-cyclin E. GADD45 also works with the cyclin-dependent kinase inhibitor p21, which can cause growth arrest as well. GADD45G is found to be involved with the p38 MAPK pathway through interactions with MAP3K4, which can be important in sex-determination. Additionally, GADD45G regulates DNA replication and repair through its interactions with PCNA. # Tissue distribution In humans, GADD45G is expressed most in the skeletal muscle, kidney and liver. This gene has a low expression in the heart, brain, spleen, lung and testis. GADD45G is highly expressed in the placenta. In the embryonic mouse, Gadd45g is expressed in the neural tube, cranial and dorsal root ganglia and the dorsal midbrain. Mammalian renal inner medullary (IM) cells routinely face and resist hypertonic stress. Such stress causes DNA damage to which IM cells respond with cell cycle arrest. All three GADD45 isoforms GADD45A, GADD45B, and GADD45G are induced by acute hypertonicity in murine IM cells. Maximum induction occurs 16-18 h after the onset of hypertonicity. GADD45G is induced more strongly (7-fold) than GADD45B (3-fold) and GADD45A (2-fold). Hypertonicity of various forms (NaCl, KCl, sorbitol, or mannitol) always induces GADD45 transcripts, whereas non-hypertonic hyperosmolality (urea) has no effect. Actinomycin D does not prevent hypertonic GADD45 induction, indicating that mRNA stabilization is the mechanism that mediates this induction. # Clinical significance In numerous kinds of cancerous cells, GADD45G is down regulated. There is a low expression due to methylation of the GADD45G promotor. This low expression can also be explained by increased NF-κB activation. GADD45G methylation is seen in many cancers. In esophageal cancer the expression level and methylation status of the gene are involved in the prognosis of esophageal squamous cell carcinoma. Demethylation of the gene can have some beneficial effects. Similar circumstances are seen in gastric cardio adenocarcinomas where GADD45G is silenced. GADD45G methylation levels are also measured in the diagnosis of pancreatic and colorectal cancers. In the pituitary gland, GADD45G is a growth suppressor. There is a loss of expression of the gene in many pituitary cancerous masses. The gene plays a role in prostate cancer as a tumor suppressor as well. In these cancerous cells, Vitamin D can induce the expression of GADD45G. GADD45G could possibly be a target of therapeutic benefit for prostate cancer. In cancerous liver cells, GADD45G is down regulated.It participates in negatively regulating the Jak-Stat3 signaling pathway. It acts as a tumor suppressor in HCC cells by promoting cell death or growth arrest. When GADD45G expression is low, liver cells may be able to bypass the growth arrest stage, leading to cancerous cells. The presence of GADD45G in the urinary system is also related to renal disease. The renal cells expressing the gene were damaged. The upregulation of Gadd45g due to hormones may account for the changes in the mouse uterus.	GADD45G Growth arrest and DNA-damage-inducible protein GADD45 gamma is a protein that in humans is encoded by the GADD45G gene on chromosome 9. GADD45G is also known as CR6, DDIT2, GRP17, OIG37, and GADD45gamma.[1] GADD45G is involved in several different processes, including sexual development,[2] human-specific brain development,[3] tumor suppression,[4] and the cellular stress response.[5] GADD45G interacts with several other proteins that are involved in DNA repair, cell cycle control, apoptosis, and senescence.[2] Low expression of GADD45G has been associated with many types of cancer.[6] # History GADD45G was originally cloned by Beadling under the name CR6 in 1993. In this experiment, several genes including GADD45G were noted for being induced by IL-2, and they were identified as immediate early response genes in T lymphocytes.[7] Its role as a tumor suppressor was discovered in 1999 by Zhang.[8] It received the name OIG37 from Nakayama due to its regulation by Oncostatin M, which was found to be able to inhibit growth.[9] Finally, it also became known as Gadd-related protein 17 during its isolation from a cDNA library by Suzuki due to its homology with Gadd45.[1] # Structure and function GADD45G is a member of a group of genes whose transcript levels are increased following stressful growth arrest conditions and treatment with DNA-damaging agents. The protein encoded by this gene responds to environmental stresses by mediating activation of the p38/JNK pathway via MTK1/MEKK4 kinase.[10] GADD45G is in turn regulated upstream by NF-κB.[4] The crystal structure of GADD45G reveals a dimer made of four parallel helices. The central region contains a highly acidic patch where it allows for interaction with cdc2, PCNA, and p21. The parallel isoform of GADD45G is the active form.[11] This gene plays a role in cell cycle regulation. GADD45G prevents the kinase ability of the cyclin b1/Cdk1 complex in a fashion that does not break apart the complex. It plays a role in the activation of the S and G2/M checkpoints.[12] In the male sexual development pathway, GADD45G is essential for activating SRY, leading to proper formation of the gonads and sex-determination. This could occur through GADD45G interaction with the p38 MAPK signaling pathway.[2] Deletion of an enhancer close to the GADD45G gene is correlated to increased proliferation of neuronal cells, which could account for part of the difference in neural development between humans and other species.[3] The deletion of the enhancer reduces the expression of the gene in the forebrain allowing for more brain growth in humans.[13] GADD45G is involved with dental epithelial cell proliferation. GADD45G is expressed in enamel knots, where it regulates gene expression and cell growth. The gene modulates p21-mediated epithelial cell proliferation by activating the p38 MAPK pathway during the development of teeth.[14] There is differential expression of the Xenopus homolog of GADD45G in embryonic development. It plays a large role in neural and brain development with GADD45A. GADD45G and GADD45A knockdowns are related to improper gastrulation, defective head growth, and shorter axes. GADD45G and GADD45A act redundantly to control cell growth, allow the cells to move from pluripotentcy helping cells differentiate.[15] # Interactions GADD45G carries out its many previously stated functions with many different interactions. GADD45G was found to inhibit Cdk1 kinase activity, which would cause disruption of cell growth.[12] It also interacts with CRIF, which causes the inhibition of Cdc2-cyclin B1 and Cdk-cyclin E.[16] GADD45 also works with the cyclin-dependent kinase inhibitor p21, which can cause growth arrest as well.[17] GADD45G is found to be involved with the p38 MAPK pathway through interactions with MAP3K4, which can be important in sex-determination.[18] Additionally, GADD45G regulates DNA replication and repair through its interactions with PCNA.[9][17] # Tissue distribution In humans, GADD45G is expressed most in the skeletal muscle, kidney and liver. This gene has a low expression in the heart, brain, spleen, lung and testis.[4] GADD45G is highly expressed in the placenta.[19] In the embryonic mouse, Gadd45g is expressed in the neural tube, cranial and dorsal root ganglia and the dorsal midbrain.[20] Mammalian renal inner medullary (IM) cells routinely face and resist hypertonic stress. Such stress causes DNA damage to which IM cells respond with cell cycle arrest. All three GADD45 isoforms GADD45A, GADD45B, and GADD45G are induced by acute hypertonicity in murine IM cells. Maximum induction occurs 16-18 h after the onset of hypertonicity. GADD45G is induced more strongly (7-fold) than GADD45B (3-fold) and GADD45A (2-fold). Hypertonicity of various forms (NaCl, KCl, sorbitol, or mannitol) always induces GADD45 transcripts, whereas non-hypertonic hyperosmolality (urea) has no effect. Actinomycin D does not prevent hypertonic GADD45 induction, indicating that mRNA stabilization is the mechanism that mediates this induction.[21] # Clinical significance In numerous kinds of cancerous cells, GADD45G is down regulated.[6] There is a low expression due to methylation of the GADD45G promotor.[14] This low expression can also be explained by increased NF-κB activation.[22] GADD45G methylation is seen in many cancers. In esophageal cancer the expression level and methylation status of the gene are involved in the prognosis of esophageal squamous cell carcinoma. Demethylation of the gene can have some beneficial effects.[14] Similar circumstances are seen in gastric cardio adenocarcinomas where GADD45G is silenced.[23] GADD45G methylation levels are also measured in the diagnosis of pancreatic and colorectal cancers.[24] In the pituitary gland, GADD45G is a growth suppressor. There is a loss of expression of the gene in many pituitary cancerous masses.[25] The gene plays a role in prostate cancer as a tumor suppressor as well. In these cancerous cells, Vitamin D can induce the expression of GADD45G.[26] GADD45G could possibly be a target of therapeutic benefit for prostate cancer.[27] In cancerous liver cells, GADD45G is down regulated.It participates in negatively regulating the Jak-Stat3 signaling pathway. It acts as a tumor suppressor in HCC cells by promoting cell death or growth arrest. When GADD45G expression is low, liver cells may be able to bypass the growth arrest stage, leading to cancerous cells.[6] The presence of GADD45G in the urinary system is also related to renal disease. The renal cells expressing the gene were damaged.[28] The upregulation of Gadd45g due to hormones may account for the changes in the mouse uterus.[29]	https://www.wikidoc.org/index.php/GADD45G
b19ac01e1560ca425cbe7b8fce349b2244486067	wikidoc	GALNT14	GALNT14 Polypeptide N-acetylgalactosaminyltransferase 14 is an enzyme that in humans is encoded by the GALNT14 gene. GALNT14 (EC 2.4.1.41) belongs to a large subfamily of glycosyltransferases residing in the Golgi apparatus. GALNT enzymes catalyze the first step in the O-glycosylation of mammalian proteins by transferring N-acetyl-D-galactosamine (GalNAc) to peptide substrates. SNPs on GALNT14 have been shown to be associated to the chemotherapy responses of patients with advanced hepatocellular carcinoma.	GALNT14 Polypeptide N-acetylgalactosaminyltransferase 14 is an enzyme that in humans is encoded by the GALNT14 gene.[1][2] GALNT14 (EC 2.4.1.41) belongs to a large subfamily of glycosyltransferases residing in the Golgi apparatus. GALNT enzymes catalyze the first step in the O-glycosylation of mammalian proteins by transferring N-acetyl-D-galactosamine (GalNAc) to peptide substrates.[supplied by OMIM][2] SNPs on GALNT14 have been shown to be associated to the chemotherapy responses of patients with advanced hepatocellular carcinoma.[3][4][5][6]	https://www.wikidoc.org/index.php/GALNT14
fa5cda879cff7ff16cb4f8fbb630988c0bd0f527	wikidoc	GLYCAM1	GLYCAM1 Glycosylation-dependent cell adhesion molecule-1 (GLYCAM1) is a proteoglycan ligand expressed on cells of the high endothelial venules in lymphoid tissues. It is the ligand for the receptor L-selectin allowing for naive lymphocytes to exit the bloodstream into lymphoid tissues. GLYCAM1 binds to L-selectin by presenting one or more O-linked carbohydrates to the lectin domain of the leukocyte cell surface selectin. Data suggests that GLYCAM1 is a hormone-regulated milk protein that is part of the milk mucin complex. GlyCAM-1 is expressed exclusively on high endothelial venules. It is unclear how GlyCAM-1 is attached to the membrane as it lacks a transmembrane region.	GLYCAM1 Glycosylation-dependent cell adhesion molecule-1 (GLYCAM1) is a proteoglycan ligand expressed on cells of the high endothelial venules in lymphoid tissues. It is the ligand for the receptor L-selectin allowing for naive lymphocytes to exit the bloodstream into lymphoid tissues.[1][2] GLYCAM1 binds to L-selectin by presenting one or more O-linked carbohydrates to the lectin domain of the leukocyte cell surface selectin.[citation needed] Data suggests that GLYCAM1 is a hormone-regulated milk protein that is part of the milk mucin complex.[3] GlyCAM-1 is expressed exclusively on high endothelial venules. It is unclear how GlyCAM-1 is attached to the membrane as it lacks a transmembrane region.[1] # External links - GlyCAM-1 at the US National Library of Medicine Medical Subject Headings (MeSH)	https://www.wikidoc.org/index.php/GLYCAM1
ed001c169f12fa889d1ba7a2b1e2ccf2ab98f48f	wikidoc	GRASP55	GRASP55 Golgi reassembly-stacking protein of 55 kDa (GRASP55) also known as golgi reassembly-stacking protein 2 (GORASP2) is a protein that in humans is encoded by the GORASP2 gene. It was identified by its homology with GRASP65 and the protein's amino acid sequence was determined by analysis of a molecular clone of its complementary DNA. The first (N-terminus) 212 amino acid residues of GRASP55 are highly homologous to those of GRASP65, but the remainder of the 454 amino acid residues are highly diverged from GRASP65. The conserved region is known as the GRASP domain, and it is conserved among GRASPs of a wide variety of eukaryotes, but not plants. The C-terminus portion of the molecule is called the SPR domain (serine, proline-rich). GRASP55 is more closely related to homologues in other species, suggesting that GRASP55 is ancestral to GRASP65. GRASP55 is found associated with the medial and trans cisternae of the Golgi apparatus. # Function GRASP55 is involved in establishing the structure of the Golgi apparatus. It is a peripheral membrane protein located on the Golgi cisterna, and it can bind to another GRASP55 located on an adjacent cisterna through the GRASP domain, thus linking the cisternae together through multiple protein–protein interactions. GRASP55 is attached to the membrane in two ways; it is myristylated, which attaches it directly to the lipid bilayer; it is also bound indirectly by binding to golgin-45, which binds to a Rab protein, which itself is lipidated and thus anchored to the membrane. The structure of the Golgi is disrupted during mitosis, and phosphorylation of the SPR domains of GRASP55 and GRASP65 regulate that disruption, GRASP55 may also be involved in forming Golgi ribbons, but the evidence is mixed. # Other interactions GRASP55 has been shown to interact with TGF alpha, TMED2 and GOLGA2.	GRASP55 Golgi reassembly-stacking protein of 55 kDa (GRASP55) also known as golgi reassembly-stacking protein 2 (GORASP2) is a protein that in humans is encoded by the GORASP2 gene.[1][2] It was identified by its homology with GRASP65 and the protein's amino acid sequence was determined by analysis of a molecular clone of its complementary DNA.[1] The first (N-terminus) 212 amino acid residues of GRASP55 are highly homologous to those of GRASP65, but the remainder of the 454 amino acid residues are highly diverged from GRASP65.[1] The conserved region is known as the GRASP domain, and it is conserved among GRASPs of a wide variety of eukaryotes, but not plants.[2][3] The C-terminus portion of the molecule is called the SPR domain (serine, proline-rich).[3] GRASP55 is more closely related to homologues in other species, suggesting that GRASP55 is ancestral to GRASP65.[3] GRASP55 is found associated with the medial and trans cisternae of the Golgi apparatus.[3] # Function GRASP55 is involved in establishing the structure of the Golgi apparatus.[3][2] It is a peripheral membrane protein located on the Golgi cisterna, and it can bind to another GRASP55 located on an adjacent cisterna through the GRASP domain, thus linking the cisternae together through multiple protein–protein interactions.[3][4] GRASP55 is attached to the membrane in two ways; it is myristylated, which attaches it directly to the lipid bilayer; it is also bound indirectly by binding to golgin-45, which binds to a Rab protein, which itself is lipidated and thus anchored to the membrane.[3] The structure of the Golgi is disrupted during mitosis, and phosphorylation of the SPR domains of GRASP55 and GRASP65 regulate that disruption,[5][4] GRASP55 may also be involved in forming Golgi ribbons, but the evidence is mixed.[3][5] # Other interactions GRASP55 has been shown to interact with TGF alpha,[6] TMED2[6] and GOLGA2.[1][6][7]	https://www.wikidoc.org/index.php/GRASP55
65eb3104b7a3bdea305d15db9b5ab7ec5e5bd6ae	wikidoc	GRASP65	GRASP65 Golgi reassembly-stacking protein of 65 kDa (GRASP65) also known as Golgi reassembly-stacking protein 1 (GORASP1) is a protein that in humans is encoded by the GORASP1 gene. # Function The Golgi complex plays a key role in the sorting and modification of proteins exported from the endoplasmic reticulum. The GRASP65 protein is a peripheral membrane protein anchored to the lipid bilayer through myristoylation of a glycine residue near the protein's amino terminus. It is involved in establishing the stacked structure of the Golgi apparatus and linking the stacks into larger ribbons in verterbate cells. It is a caspase-3 substrate, and cleavage of this encoded protein contributes to Golgi fragmentation in apoptosis. GRASP65 can form a complex with the Golgi matrix protein GM130, and this complex binds to the vesicle docking protein p115. Several alternatively spliced transcript variants of this gene have been identified, but their full-length natures have not been determined. # Structure GRASP65 contains two PDZ domains in the amino-terminal GRASP domain (amino acid residues 2–210), that comprises approximately half of the protein. The GRASP region interacts with the Golgi matrix protein GM130 as well as an intrinsically disordered region in the C-terminus. - GRASP65 superhelix, topview GRASP65 superhelix, topview - File:4REY top helix.png - File:4REY tilted helix.png - GRASP65 superhelix, side view GRASP65 superhelix, side view - File:4REY side helix.png # Interactions GORASP1 has been shown to interact with TGF alpha, TMED2 and GOLGA2. # Notes - ↑ This is shown in the external link entitled "Molecular models of GRASP65/GM130/P115-mediated cis-cisternae membrane stacking and vesicle tethering."	GRASP65 Golgi reassembly-stacking protein of 65 kDa (GRASP65) also known as Golgi reassembly-stacking protein 1 (GORASP1) is a protein that in humans is encoded by the GORASP1 gene.[1] # Function The Golgi complex plays a key role in the sorting and modification of proteins exported from the endoplasmic reticulum. The GRASP65 protein is a peripheral membrane protein anchored to the lipid bilayer through myristoylation of a glycine residue near the protein's amino terminus.[3] It is involved in establishing the stacked structure of the Golgi apparatus and linking the stacks into larger ribbons in verterbate cells.[3] It is a caspase-3 substrate, and cleavage of this encoded protein contributes to Golgi fragmentation in apoptosis.[4][5] GRASP65 can form a complex with the Golgi matrix protein GM130, and this complex binds to the vesicle docking protein p115.[3][lower-alpha 1] Several alternatively spliced transcript variants of this gene have been identified, but their full-length natures have not been determined.[1] # Structure GRASP65 contains two PDZ domains in the amino-terminal GRASP domain (amino acid residues 2–210), that comprises approximately half of the protein. The GRASP region interacts with the Golgi matrix protein GM130 as well as an intrinsically disordered region in the C-terminus.[3][6] - GRASP65 superhelix, topview[3] GRASP65 superhelix, topview[3] - File:4REY top helix.png - File:4REY tilted helix.png - GRASP65 superhelix, side view[3] GRASP65 superhelix, side view[3] - File:4REY side helix.png # Interactions GORASP1 has been shown to interact with TGF alpha,[7] TMED2[7] and GOLGA2.[7][8][9] # Notes - ↑ This is shown in the external link entitled "Molecular models of GRASP65/GM130/P115-mediated cis-cisternae membrane stacking and vesicle tethering."	https://www.wikidoc.org/index.php/GRASP65
c4e55076aaccf6190921f1a76888548c1ee17ba6	wikidoc	GUCY1B3	GUCY1B3 Guanylate cyclase soluble subunit beta-1 is an enzyme that in humans is encoded by the GUCY1B3 gene. # Function Soluble guanylate cyclase (sGC), a heterodimeric protein consisting of an alpha and a beta subunit, catalyzes the conversion of GTP to the second messenger cGMP and functions as the main receptor for nitric oxide and nitrovasodilator drugs. # Interactions GUCY1B3 has been shown to interact with Heat shock protein 90kDa alpha (cytosolic), member A1 and Endothelial NOS.	GUCY1B3 Guanylate cyclase soluble subunit beta-1 is an enzyme that in humans is encoded by the GUCY1B3 gene.[1][2] # Function Soluble guanylate cyclase (sGC), a heterodimeric protein consisting of an alpha and a beta subunit, catalyzes the conversion of GTP to the second messenger cGMP and functions as the main receptor for nitric oxide and nitrovasodilator drugs.[2] # Interactions GUCY1B3 has been shown to interact with Heat shock protein 90kDa alpha (cytosolic), member A1[3] and Endothelial NOS.[3]	https://www.wikidoc.org/index.php/GUCY1B3
bc4f3a9badc111d59eb4d4065230cca62b2e51ff	wikidoc	GUSTO-I	GUSTO-I GUSTO-I = Global Utilization of Streptokinase and t-PA for Occluded Coronary Arteries - I Trial # Overview The GUSTO-I trial randomized 41 021 patients with acute myocardial infarction and ST segment elevation within 6 hours of symptom onset to one of four thrombolytic strategies. Enrollment was not restricted because of age or presentation in cardiogenic shock. Patients were excluded if they had prior stroke, active or recent bleeding, recent trauma or major surgery, non compressible vascular punctures, or previous treatment with streptokinase or anistreplase. # Treatments Patients were randomized to receive streptokinase 1.5 million U infused for 1 hour and subcutaneous heparin 12 500 U twice daily beginning 4 hours after the commencement of streptokinase; streptokinase 1.5 million U for 1 hour and intravenous heparin, beginning with a 5000-U bolus and followed by an infusion of 1000 U adjusted to maintain an activated partial thromboplastin time (aPTT) of 60 to 85 seconds; accelerated t-PA, bolus of 15 mg and infusions of 0.75 mg/kg for 30 minutes (up to 50 mg) and 0.5 mg/kg (up to 35 mg) for the next hour, with the same intravenous heparin regimen; or combination t-PA (1 mg/kg for 1 hour, up to 90 mg, with 10% given as a bolus) and streptokinase (1 million U for 1 hour) given simultaneously through separate cannulas, with the same intravenous heparin regimen. # End Points The primary end point was all-cause 30-day mortality. Inpatient mortality data were recorded on the main case report form. Postdischarge mortality data were collected by return postcard or by telephone follow-up. Mortality status at 30 days was known for 40 946 patients (99.8%). One-year follow-up data were available for 39 119 patients (95.3%). Secondary end points included stroke, death or stroke, and death or nonfatal, disabling stroke. Cases of neurological deficit that were fatal or persisted for 24 hours were reviewed by a blinded, independent committee. Events were classified as primary intracranial hemorrhage, non hemorrhagic infarction, hemorrhagic conversion of infarction, and unknown. Anatomic or diagnostic confirmation of stroke was obtained in 93% of the cases. Bleeding complications were classified as severe or life threatening if they were intracranial or resulted in hemodynamic compromise that required intervention. Moderate bleeding was defined as bleeding that required transfusion. # Statistical Methods To describe changes in baseline characteristics and clinical outcomes with age, we arbitrarily categorized patients into four groups: 85 years. Discrete variables are summarized with frequencies and percentages; continuous variables are described with means ± SDs or medians and 25th and 75th percentiles. Clinical outcome variables were tabulated both by age category and by treatment assignment. Kaplan-Meier estimates for 24-hour, 30-day, and 1-year mortality were calculated to show the treatment effects across the different age groups. These age groups were chosen to allow ready visual inspection of trends in the data. Ordinary least-squares regression was used to determine the statistical significance of the relations between age and the other baseline characteristics. Logistic regression was used to evaluate the statistical significance of the relation between age and the 30-day outcomes of interest. Cox proportional hazard modeling techniques were used to determine the statistical significance of the relation between 1-year mortality and age. For both types of mortality models, the shapes of the relations were evaluated with cubic spline functions.	GUSTO-I Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor-In-Chief: Cafer Zorkun, M.D., Ph.D. [2] GUSTO-I = Global Utilization of Streptokinase and t-PA for Occluded Coronary Arteries - I Trial # Overview The GUSTO-I trial randomized 41 021 patients with acute myocardial infarction and ST segment elevation within 6 hours of symptom onset to one of four thrombolytic strategies. Enrollment was not restricted because of age or presentation in cardiogenic shock. Patients were excluded if they had prior stroke, active or recent bleeding, recent trauma or major surgery, non compressible vascular punctures, or previous treatment with streptokinase or anistreplase. # Treatments Patients were randomized to receive streptokinase 1.5 million U infused for 1 hour and subcutaneous heparin 12 500 U twice daily beginning 4 hours after the commencement of streptokinase; streptokinase 1.5 million U for 1 hour and intravenous heparin, beginning with a 5000-U bolus and followed by an infusion of 1000 U adjusted to maintain an activated partial thromboplastin time (aPTT) of 60 to 85 seconds; accelerated t-PA, bolus of 15 mg and infusions of 0.75 mg/kg for 30 minutes (up to 50 mg) and 0.5 mg/kg (up to 35 mg) for the next hour, with the same intravenous heparin regimen; or combination t-PA (1 mg/kg for 1 hour, up to 90 mg, with 10% given as a bolus) and streptokinase (1 million U for 1 hour) given simultaneously through separate cannulas, with the same intravenous heparin regimen. # End Points The primary end point was all-cause 30-day mortality. Inpatient mortality data were recorded on the main case report form. Postdischarge mortality data were collected by return postcard or by telephone follow-up. Mortality status at 30 days was known for 40 946 patients (99.8%). One-year follow-up data were available for 39 119 patients (95.3%). Secondary end points included stroke, death or stroke, and death or nonfatal, disabling stroke. Cases of neurological deficit that were fatal or persisted for 24 hours were reviewed by a blinded, independent committee. Events were classified as primary intracranial hemorrhage, non hemorrhagic infarction, hemorrhagic conversion of infarction, and unknown. Anatomic or diagnostic confirmation of stroke was obtained in 93% of the cases. Bleeding complications were classified as severe or life threatening if they were intracranial or resulted in hemodynamic compromise that required intervention. Moderate bleeding was defined as bleeding that required transfusion. # Statistical Methods To describe changes in baseline characteristics and clinical outcomes with age, we arbitrarily categorized patients into four groups: <65, 65 to 74, 75 to 85, and >85 years. Discrete variables are summarized with frequencies and percentages; continuous variables are described with means ± SDs or medians and 25th and 75th percentiles. Clinical outcome variables were tabulated both by age category and by treatment assignment. Kaplan-Meier estimates for 24-hour, 30-day, and 1-year mortality were calculated to show the treatment effects across the different age groups. These age groups were chosen to allow ready visual inspection of trends in the data. Ordinary least-squares regression was used to determine the statistical significance of the relations between age and the other baseline characteristics. Logistic regression was used to evaluate the statistical significance of the relation between age and the 30-day outcomes of interest. Cox proportional hazard modeling techniques were used to determine the statistical significance of the relation between 1-year mortality and age. For both types of mortality models, the shapes of the relations were evaluated with cubic spline functions.[1]	https://www.wikidoc.org/index.php/GUSTO-I
ac0bfdf02449b12a14246bbd594ed7322f4227da	wikidoc	Galanin	Galanin Galanin is a neuropeptide encoded by the GAL gene, that is widely expressed in the brain, spinal cord, and gut of humans as well as other mammals. Galanin signaling occurs through three G protein-coupled receptors. The functional role of galanin remains largely unknown; however, galanin is predominantly involved in the modulation and inhibition of action potentials in neurons. Galanin has been implicated in many biologically diverse functions, including: nociception, waking and sleep regulation, cognition, feeding, regulation of mood, regulation of blood pressure, it also has roles in development as well as acting as a trophic factor. Galanin neurons in the medial preoptic area of the hypothalamus may govern parental behaviour. Galanin is linked to a number of diseases including Alzheimer's disease, epilepsy as well as depression, eating disorders and cancer. Galanin appears to have neuroprotective activity as its biosynthesis is increased 2-10 fold upon axotomy in the peripheral nervous system as well as when seizure activity occurs in the brain. It may also promote neurogenesis. Galanin is predominantly an inhibitory, hyperpolarizing neuropeptide and as such inhibits neurotransmitter release. Galanin is often co-localized with classical neurotransmitters such as acetylcholine, serotonin, and norepinephrine, and also with other neuromodulators such as neuropeptide Y, substance P, and vasoactive intestinal peptide. # Discovery Galanin was first identified from porcine intestinal extracts in 1978 by Professor Viktor Mutt and colleagues at the Karolinska Institute, Sweden using a chemical assay technique that detects peptides according to its C-terminal alanine amide structure. Galanin is so-called because it contains an N-terminal glycine residue and a C-terminal alanine. The structure of galanin was determined in 1983 by the same team, and the cDNA of galanin was cloned from a rat anterior pituitary library in 1987. # Tissue distribution Galanin is located predominantly in the central nervous system and gastrointestinal tract. Within the central nervous system, highest concentrations are found in the hypothalamus, with lower levels in the cortex and brainstem. Gastrointestinal galanin is most abundant in the duodenum, with lower concentrations in the stomach, small intestine, and colon. # Structure Galanin is a peptide consisting of a chain of 29 amino acids (30 amino acids in humans) produced from the cleavage of a 123-amino acid protein known as prepro galanin, which is encoded by the GAL gene. The sequence of this gene is highly conserved among mammals, showing over 85% homology between rat, mouse, porcine, bovine, and human sequences. In these animal forms, the first 15 amino acids from the N-terminus are identical, but amino acids differ at several positions on the C-terminal end of the protein. These slight differences in protein structure have far-reaching implications on their function. For example, porcine and rat galanin inhibit glucose-induced insulin secretion in rats and dogs but have no effect on insulin secretion in humans. This demonstrates that it is essential to study the effects of galanin and other regulatory peptides in their autologous species. The galanin family of protein consists of four proteins, of which GAL was the first to be identified. The second was galanin message-associated protein (GMAP), a 59- or 60-amino acid peptide also formed from the cleavage of prepro galanin. The other two peptides, galanin-like peptide (GALP) and alarin, were identified relatively recently and are both encoded for in the same gene, the prepro GALP gene. GALP and alarin are produced by different post-transcriptional splicing of this gene. # Receptors Galanin signalling occurs through three classes of receptors, GALR1, GALR2, and GALR3, which are all part of the G protein-coupled receptor (GPCR) superfamily. Galanin receptors are expressed in the central nervous system, in the pancreas, and on solid tumours. The level of expression of the different receptors varies at each location, and this distribution changes after injury to neurons. Experiments into the function of the receptor subtypes involve mostly genetic knockout mice. The location of the receptor and the combination of receptors that are inhibited or stimulated heavily affect the outcome of galanin signalling. # Clinical characteristics ## Alzheimer's disease One of the pathological features of the brain in the later stages of Alzheimer's disease is the presence of overgrown GAL-containing fibres innervating the surviving cholinergic neurons. Another feature is an increase in the expression of GAL and GAL receptors, in which increases of up to 200% have been observed in postmortem brains of Alzheimer's patients. The cause and role of this increase is poorly understood. It has been suggested that the hyper-innervation acts to promote the death of these neurons and that the inhibitory effect of galanin on cholinergic neurons worsened the degeneration of cognitive function in patients by decreasing the amount of acetylcholine available to these neurons. A second hypothesis has been generated based on data that suggest GAL is involved in protecting the hippocampus from excitotoxic damage and the neurons in the cholinergic basal forebrain from amyloid toxicity. Studies of gene expression of CBF tissue suggests that the hyperinnervation of cholinergic neurons by GAL up regulates the transcription of factors that promote neuron function and survival. It is still unclear as to whether galanin acts to protect cholinergic neurons and promote their firing or whether it worsens the symptoms of this disease. ## Epilepsy Galanin in the hippocampus is an inhibitor of glutamate but not of GABA. This means that galanin is capable of increasing the seizure threshold and, therefore, is expected to act as an anticonvulsant. To be specific, GalR1 has been linked to the suppression of spontaneous seizures. An agonist antiepileptic drug candidate is NAX 5055. ## In development It has been shown that galanin plays a role in the control of the early post-natal neural development of the dorsal root ganglion (DRG). Galanin-mutant animals show a 13% decrease in the number of adult DRG cells as well as a 24% decrease in the percentage of cells expressing substance P. This suggests that the cell loss by apoptosis that usually occurs in the developing DRG is regulated by galanin and that the absence of galanin results in an increase in the number of cells that die. ## After injury In vitro experiments show that DRG cells removed from galanin mutants have impaired abilities to extend neurites in culture, in that the number of cells producing neurites is decreased by a third and the mean length of these processes was halved when compared to wild-type controls. In vivo, many of the actions of galanin in the brain after an injury are similar to those observed in the developing DRG. Adult mutant animals have been shown to be 35% less capable of regenerating the sciatic nerve after crush injury, which is linked to long-term functional problems. ## Parental role in mice A report has indicated that Galanin-expressing neurons in the medial preoptic area of the brain are responsible for regulating aggression towards pups by male mice.	Galanin Galanin is a neuropeptide encoded by the GAL gene,[1] that is widely expressed in the brain, spinal cord, and gut of humans as well as other mammals. Galanin signaling occurs through three G protein-coupled receptors.[2] The functional role of galanin remains largely unknown; however, galanin is predominantly involved in the modulation and inhibition of action potentials in neurons. Galanin has been implicated in many biologically diverse functions, including: nociception, waking and sleep regulation, cognition, feeding, regulation of mood, regulation of blood pressure, it also has roles in development as well as acting as a trophic factor.[3] Galanin neurons in the medial preoptic area of the hypothalamus may govern parental behaviour.[4] Galanin is linked to a number of diseases including Alzheimer's disease, epilepsy as well as depression, eating disorders and cancer.[5][6] Galanin appears to have neuroprotective activity as its biosynthesis is increased 2-10 fold upon axotomy in the peripheral nervous system as well as when seizure activity occurs in the brain. It may also promote neurogenesis.[2] Galanin is predominantly an inhibitory, hyperpolarizing neuropeptide[7] and as such inhibits neurotransmitter release. Galanin is often co-localized with classical neurotransmitters such as acetylcholine, serotonin, and norepinephrine, and also with other neuromodulators such as neuropeptide Y, substance P, and vasoactive intestinal peptide.[8] # Discovery Galanin was first identified from porcine intestinal extracts in 1978 by Professor Viktor Mutt and colleagues at the Karolinska Institute, Sweden[9] using a chemical assay technique that detects peptides according to its C-terminal alanine amide structure. Galanin is so-called because it contains an N-terminal glycine residue and a C-terminal alanine.[10] The structure of galanin was determined in 1983 by the same team, and the cDNA of galanin was cloned from a rat anterior pituitary library in 1987.[9] # Tissue distribution Galanin is located predominantly in the central nervous system and gastrointestinal tract. Within the central nervous system, highest concentrations are found in the hypothalamus, with lower levels in the cortex and brainstem. Gastrointestinal galanin is most abundant in the duodenum, with lower concentrations in the stomach, small intestine, and colon.[11] # Structure Galanin is a peptide consisting of a chain of 29 amino acids (30 amino acids in humans) produced from the cleavage of a 123-amino acid protein known as prepro galanin, which is encoded by the GAL gene.[1] The sequence of this gene is highly conserved among mammals, showing over 85% homology between rat, mouse, porcine, bovine, and human sequences.[8] In these animal forms, the first 15 amino acids from the N-terminus are identical, but amino acids differ at several positions on the C-terminal end of the protein. These slight differences in protein structure have far-reaching implications on their function. For example, porcine and rat galanin inhibit glucose-induced insulin secretion in rats and dogs but have no effect on insulin secretion in humans. This demonstrates that it is essential to study the effects of galanin and other regulatory peptides in their autologous species.[12] The galanin family of protein consists of four proteins, of which GAL was the first to be identified. The second was galanin message-associated protein (GMAP), a 59- or 60-amino acid peptide also formed from the cleavage of prepro galanin.[10] The other two peptides, galanin-like peptide (GALP) and alarin, were identified relatively recently and are both encoded for in the same gene, the prepro GALP gene. GALP and alarin are produced by different post-transcriptional splicing of this gene.[13] # Receptors Galanin signalling occurs through three classes of receptors, GALR1, GALR2, and GALR3, which are all part of the G protein-coupled receptor (GPCR) superfamily. Galanin receptors are expressed in the central nervous system, in the pancreas, and on solid tumours. The level of expression of the different receptors varies at each location, and this distribution changes after injury to neurons.[2] Experiments into the function of the receptor subtypes involve mostly genetic knockout mice. The location of the receptor and the combination of receptors that are inhibited or stimulated heavily affect the outcome of galanin signalling.[2] # Clinical characteristics ## Alzheimer's disease One of the pathological features of the brain in the later stages of Alzheimer's disease is the presence of overgrown GAL-containing fibres innervating the surviving cholinergic neurons.[14] Another feature is an increase in the expression of GAL and GAL receptors, in which increases of up to 200% have been observed in postmortem brains of Alzheimer's patients.[2][13] The cause and role of this increase is poorly understood.[14][15] It has been suggested that the hyper-innervation acts to promote the death of these neurons and that the inhibitory effect of galanin on cholinergic neurons worsened the degeneration of cognitive function in patients by decreasing the amount of acetylcholine available to these neurons.[2][14] A second hypothesis has been generated based on data that suggest GAL is involved in protecting the hippocampus from excitotoxic damage and the neurons in the cholinergic basal forebrain from amyloid toxicity.[16] Studies of gene expression of CBF tissue suggests that the hyperinnervation of cholinergic neurons by GAL up regulates the transcription of factors that promote neuron function and survival. It is still unclear as to whether galanin acts to protect cholinergic neurons and promote their firing or whether it worsens the symptoms of this disease. ## Epilepsy Galanin in the hippocampus is an inhibitor of glutamate but not of GABA. This means that galanin is capable of increasing the seizure threshold [2] and, therefore, is expected to act as an anticonvulsant. To be specific, GalR1 has been linked to the suppression of spontaneous seizures.[17][18] An agonist antiepileptic drug candidate is NAX 5055.[19][20] ## In development It has been shown that galanin plays a role in the control of the early post-natal neural development of the dorsal root ganglion (DRG).[9] Galanin-mutant animals show a 13% decrease in the number of adult DRG cells as well as a 24% decrease in the percentage of cells expressing substance P. This suggests that the cell loss by apoptosis that usually occurs in the developing DRG is regulated by galanin and that the absence of galanin results in an increase in the number of cells that die. ## After injury In vitro experiments show that DRG cells removed from galanin mutants have impaired abilities to extend neurites in culture, in that the number of cells producing neurites is decreased by a third and the mean length of these processes was halved when compared to wild-type controls. In vivo, many of the actions of galanin in the brain after an injury are similar to those observed in the developing DRG. Adult mutant animals have been shown to be 35% less capable of regenerating the sciatic nerve after crush injury, which is linked to long-term functional problems. ## Parental role in mice A report has indicated that Galanin-expressing neurons in the medial preoptic area of the brain are responsible for regulating aggression towards pups by male mice.[4]	https://www.wikidoc.org/index.php/Galanin
f5eb3f42eccbd349f32f82979fb06c4f24c1e24a	wikidoc	Gary Sy	Gary Sy Gary S. Sy, popularly known as Dr. Gary Sy, is a renowned medical practitioner, television host, radio broadcaster, columnist, and author in the Philippines. He is one of the few doctors specializing in geriatrics in the country. # Medical leadership and advocacy Sy is the Medical Director of the Life Extension Medical Center located in Suite E, Garden Plaza Hotel, 1370 Gen. Luna St., Paco, Manila. He travels throughout the Philippines and abroad, delivering free lectures on important health issues and rendering free medical consultations to the general public. He is particularly interested in addressing the concerns of the old and individuals dealing with senility. # Education Sy obtained a Bachelor of Science in Medical Technology in 1987 from the Far Eastern University in Manila. He attended the Fatima College of Medicine in Valenzuela, and earned a Doctor of Medicine degree in 1992. He entered the Internship Program at the Clark Air Base in the United States Air Force Regional Medical Center. He took postgraduate courses in Occupational Health and Safety at the University of the Philippines College of Public Health in 1994; Sports Medicine and Family Medicine at the University of Santo Tomas Faculty of Medicine and Surgery in 1996; Gerontology and Geriatrics at the Philippine College of Gerontology and Geriatrics and in Bucharest, Romania, in 1999. # Career Sy is the Medical Director of the Life Extension Medical Center, a medium-sized hospital rendering free services to indigent patients in the country. The hospital was awarded as the Most Outstanding Geriatric Treatment Center' by the Parangal ng Bayan Foundation's The Who's Who in the Philippines Awards in September 17, 2001 at the Philamlife Theater in Manila. He is also the Medical Director of Herbcare International; a Medical Consultant of the Philippine United Senior Citizen Association (PUSCA); and a Board Member of the Philippine College of Gerontologist & Geriatrics, Inc. # Broadcasting Sy is a regular Medical Broadcaster in DZMM through his Sunday weekly radio program Gabay sa Kalusugan (Your Guide to Health). He is also a regular Medical Television Host in RPN-9 through his Sunday weekly television medical talkshow, Health TV. He appears regularly in several radio programs in Metro Manila, including: DZRH (666 kHz) "Operation Tulong" with Andy Verde; DZME (1530 kHz) with Rod Navarro; DZRH 666 kHz with Tiya Dely Magpayo; DZBB 594 kHz with German Moreno (Kuya Germs) and Manolo Favis; DZMM 630 kHz with Jimmy Licauco; and DZBB 594 kHz with Manang Rose. # Publishing Sy has authored two medical books, Gabay sa Kalusugan: Part I, and Gabay sa Kalusugan: Part II. He is a regular contributor in several national dailies: the Manila Bulletin's Life Extension every Wednesday; Sunday Tonight's Optimum Health every Sunday; and Philippine News Analyzer Magazine's Doctor's Touch, a quarterly issue. # Commercial endorsements Sy is an active commercial endorser of Theraherb, a brand of virgin coconut oil (VCO) developed by Splash Nutraceutical Corporation. He also endorses Circulan for proper blood circulation. He promotes specially formulated medicinal supplements developed and distributed by Filipino-owned pharmaceutical companies. # Awards Sy has received numerous awards as a medical practitioner and broadcaster, including: the Most Outstanding Sports Medicine Physician award from the Federation of Filipino Consumers, Inc. in 1998; the Most Outstanding Young Leader Award from the Development of Filipino Youth, Inc., in 1998; the Outstanding Young Professional Awards in Medicine & Allied Sciences from the Parangal ng Bayan Awards for 1999-2000; the Outstanding Young Gerontologist of the Philippines from the Kapatiran Awards in 2000; the Outstanding Physician of the Year from the Best in Service Asia Pacific Out-Reach Development, Inc.; Young Professional Awardee in Medicine and Allied Services from the Dr. Jose Rizal Awards in 1999; and the Humanitarian Award from the Philippine United Senior Citizen Association (PUSCA) for 2000-2001; the 2000 Andres Bonifacio Grand Achievement Awardee during the 2nd Annual Mabuhay Filipino Achievers Gawad Parangal; Huwarang Pilipino Awardee for Medicine & Allied Sciences from the Top Men and Women of the New Millennium and Parangal ng Bayan Awards; and the Physician of the Philippines from the Media Special Awards of the Philippine Media Enforcers, Inc. in 2001. # Organizations Sy is a member of the Philippine College of Occupational Medicine; the Sports Medicine Association of the Philippines; the Philippine Academy of Family Physician; the Philippine Society of Hypertension; the Philippine Federation of Private Practitioner; the Philippine College of Gerontology & Geriatrics; the Philippine Association of Gerontologist, Inc.; the International Association of Gerontologists; and the American Geriatrics Society.	Gary Sy Gary S. Sy, popularly known as Dr. Gary Sy, is a renowned medical practitioner, television host, radio broadcaster, columnist, and author in the Philippines. He is one of the few doctors specializing in geriatrics in the country. # Medical leadership and advocacy Sy is the Medical Director of the Life Extension Medical Center located in Suite E, Garden Plaza Hotel, 1370 Gen. Luna St., Paco, Manila. He travels throughout the Philippines and abroad, delivering free lectures on important health issues and rendering free medical consultations to the general public. He is particularly interested in addressing the concerns of the old and individuals dealing with senility.[1] # Education Sy obtained a Bachelor of Science in Medical Technology in 1987 from the Far Eastern University in Manila. He attended the Fatima College of Medicine in Valenzuela, and earned a Doctor of Medicine degree in 1992.[1] He entered the Internship Program at the Clark Air Base in the United States Air Force Regional Medical Center. He took postgraduate courses in Occupational Health and Safety at the University of the Philippines College of Public Health in 1994; Sports Medicine and Family Medicine at the University of Santo Tomas Faculty of Medicine and Surgery in 1996; Gerontology and Geriatrics at the Philippine College of Gerontology and Geriatrics and in Bucharest, Romania, in 1999.[1] # Career Sy is the Medical Director of the Life Extension Medical Center, a medium-sized hospital rendering free services to indigent patients in the country. The hospital was awarded as the Most Outstanding Geriatric Treatment Center' by the Parangal ng Bayan Foundation's The Who's Who in the Philippines Awards in September 17, 2001 at the Philamlife Theater in Manila.[1] He is also the Medical Director of Herbcare International; a Medical Consultant of the Philippine United Senior Citizen Association (PUSCA); and a Board Member of the Philippine College of Gerontologist & Geriatrics, Inc.[1] # Broadcasting Sy is a regular Medical Broadcaster in DZMM through his Sunday weekly radio program Gabay sa Kalusugan (Your Guide to Health). He is also a regular Medical Television Host in RPN-9 through his Sunday weekly television medical talkshow, Health TV.[1] He appears regularly in several radio programs in Metro Manila, including: DZRH (666 kHz) "Operation Tulong" with Andy Verde; DZME (1530 kHz) with Rod Navarro; DZRH 666 kHz with Tiya Dely Magpayo; DZBB 594 kHz with German Moreno (Kuya Germs) and Manolo Favis; DZMM 630 kHz with Jimmy Licauco; and DZBB 594 kHz with Manang Rose.[1] # Publishing Sy has authored two medical books, Gabay sa Kalusugan: Part I, and Gabay sa Kalusugan: Part II. He is a regular contributor in several national dailies: the Manila Bulletin's Life Extension every Wednesday; Sunday Tonight's Optimum Health every Sunday; and Philippine News Analyzer Magazine's Doctor's Touch, a quarterly issue.[1] # Commercial endorsements Sy is an active commercial endorser of Theraherb, a brand of virgin coconut oil (VCO) developed by Splash Nutraceutical Corporation. He also endorses Circulan for proper blood circulation. He promotes specially formulated medicinal supplements developed and distributed by Filipino-owned pharmaceutical companies.[2] # Awards Sy has received numerous awards as a medical practitioner and broadcaster, including: the Most Outstanding Sports Medicine Physician award from the Federation of Filipino Consumers, Inc. in 1998; the Most Outstanding Young Leader Award from the Development of Filipino Youth, Inc., in 1998; the Outstanding Young Professional Awards in Medicine & Allied Sciences from the Parangal ng Bayan Awards for 1999-2000; the Outstanding Young Gerontologist of the Philippines from the Kapatiran Awards in 2000; the Outstanding Physician of the Year from the Best in Service Asia Pacific Out-Reach Development, Inc.; Young Professional Awardee in Medicine and Allied Services from the Dr. Jose Rizal Awards in 1999; and the Humanitarian Award from the Philippine United Senior Citizen Association (PUSCA) for 2000-2001; the 2000 Andres Bonifacio Grand Achievement Awardee during the 2nd Annual Mabuhay Filipino Achievers Gawad Parangal; Huwarang Pilipino Awardee for Medicine & Allied Sciences from the Top Men and Women of the New Millennium and Parangal ng Bayan Awards; and the Physician of the Philippines from the Media Special Awards of the Philippine Media Enforcers, Inc. in 2001.[1] # Organizations Sy is a member of the Philippine College of Occupational Medicine; the Sports Medicine Association of the Philippines; the Philippine Academy of Family Physician; the Philippine Society of Hypertension; the Philippine Federation of Private Practitioner; the Philippine College of Gerontology & Geriatrics; the Philippine Association of Gerontologist, Inc.; the International Association of Gerontologists; and the American Geriatrics Society.[1] # External links - Dr. Gary Sy at the Rx Pinoy Medical Directory - Splash Nutraceutical Corporation	https://www.wikidoc.org/index.php/Gary_Sy
be178bdc04d29500a0d0ec66504059b3440e0298	wikidoc	Stomach	Stomach # Overview In anatomy, the stomach is a bean-shaped hollow muscular organ of the gastrointestinal tract involved in the second phase of digestion, following mastication. The word stomach is derived from the Latin stomachus, which derives from the Greek word stomachos (Template:Polytonic). The words gastro- and gastric (meaning related to the stomach) are both derived from the Greek word gaster (Template:Polytonic). # Functions The stomach is a highly acidic environment due to gastric acid production and secretion which produces a luminal pH range usually between 1 and 4 depending on the species, food intake, time of the day, drug use, and other factors. Such an environment is able to break down large molecules (such as from food) to smaller ones so that they can eventually be absorbed from the small intestine. The human stomach can produce and secrete about 2 to 3 liters of gastric acid per day with basal secretion levels being typically highest in the evening.The body produce enzymes to break down different foods. Pepsinogen is secreted by chief cells and turns into pepsin under low pH conditions and is a necessity in protein digestion. Absorption of vitamin B12 from the small intestine is dependent on conjugation to a glycoprotein called intrinsic factor which is produced by parietal cells of the stomach. Other functions include absorbing some ions, water, and some lipid soluble compounds such as alcohol, aspirin, and caffeine. Another function of the stomach is simply a food storage cavity. # Anatomy of the human stomach The stomach lies between the esophagus and the duodenum (the first part of the small intestine). It is on the left side of the abdominal cavity. The top of the stomach lies against the diaphragm. Lying beneath the stomach is the pancreas, and the greater omentum which hangs from the greater curvature. Two smooth muscle valves, or sphincters, keep the contents of the stomach contained. They are the esophageal sphincter (found in the cardiac region) dividing the tract above, and the Pyloric sphincter dividing the stomach from the small intestine. The stomach is surrounded by parasympathetic (stimulant) and orthosympathetic (inhibitor) plexuses (anterior gastric, posterior, superior and inferior, celiac and myenteric), which regulate both the secretory activity and the motor activity of the muscles. In humans, the stomach has a volume of about 50 mL when empty. After a meal, it generally expands to hold about 1 litre of food, but it can actually expand to hold as much as 4 litres. When drinking milk it can expand to just under 6 pints, or 3.4 litres. ## Sections The stomach is divided into four sections, each of which has different cells and functions. The sections are: ## Blood supply The lesser curvature of the stomach is supplied by the right gastric artery inferiorly, and the left gastric artery superiorly, which also supplies the cardiac region. The greater curvature is supplied by the right gastroepiploic artery inferiorly and the left gastroepiploic artery superiorly. The fundus of the stomach, and also the upper portion of the greater curvature, are supplied by the short gastric artery # Histology of the human stomach ## Layers Like the other parts of the gastrointestinal tract, the stomach walls are made of the following layers, from inside to outside: ## Glands The epithelium of the stomach forms deep pits. The glands at these locations are named for the corresponding part of the stomach: Different types of cells are found at the different layers of these glands: # Control of secretion and motility The movement and the flow of chemicals into the stomach are controlled by both the autonomic nervous system and by the various digestive system hormones: Other than gastrin, these hormones all act to turn off the stomach action. This is in response to food products in the liver and gall bladder, which have not yet been absorbed. The stomach needs only to push food into the small intestine when the intestine is not busy. While the intestine is full and still digesting food, the stomach acts as storage for food. # Diseases of the stomach - Dyspepsia - Stomach ache - Peptic ulcer - Achlorhydria - Hypochlorhydria - Linitis plastica - Zollinger-Ellison syndrome - Gastroparesis - GERD - Borborygmus Historically, it was widely believed that the highly acidic environment of the stomach would keep the stomach immune from infection. However, a large number of studies have indicated that most cases of stomach ulcers, gastritis, and stomach cancer are caused by Helicobacter pylori infection. One of the ways it is able to survive in the stomach involves its urease enzymes which metabolize urea (which is normally secreted into the stomach) to ammonia and carbon dioxide which neutralizes gastric acid and thus prevents its digestion. In recent years, it has been discovered that other Helicobacter bacteria are also capable of colonizing the stomach and have been associated with gastritis. Having too little or no gastric acid is known as hypochlorhydria or achlorhydria respectively and are conditions which can have negative health impacts. Having high levels of gastric acid is called hyperchlorhydria. Many people believe that hyperchlorhydria can cause stomach ulcers. However, recent research indicates that the gastric mucosa which secretes gastric acid is acid-resistant. # Differences among animals In ruminants, such as bovines, the stomach is a large multichamber organ which hosts symbiotic bacteria that produce enzymes required for the digestion of cellulose from plant matter, primarily cellulase. The partially digested plant matter passes through each of the intestine chambers in sequence, being regurgitated and rechewed at least once in the process. In some animals (such as cats and dogs), the pH of the lumen is lower, usually between 1 and 2. In contrast, the human stomach pH is usually between 1 and 3.	Stomach Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] # Overview Template:Infobox Anatomy In anatomy, the stomach is a bean-shaped hollow muscular organ of the gastrointestinal tract involved in the second phase of digestion, following mastication. The word stomach is derived from the Latin stomachus, which derives from the Greek word stomachos (Template:Polytonic). The words gastro- and gastric (meaning related to the stomach) are both derived from the Greek word gaster (Template:Polytonic). # Functions The stomach is a highly acidic environment due to gastric acid production and secretion which produces a luminal pH range usually between 1 and 4 depending on the species, food intake, time of the day, drug use, and other factors. Such an environment is able to break down large molecules (such as from food) to smaller ones so that they can eventually be absorbed from the small intestine. The human stomach can produce and secrete about 2 to 3 liters of gastric acid per day with basal secretion levels being typically highest in the evening.The body produce enzymes to break down different foods. Pepsinogen is secreted by chief cells and turns into pepsin under low pH conditions and is a necessity in protein digestion. Absorption of vitamin B12 from the small intestine is dependent on conjugation to a glycoprotein called intrinsic factor which is produced by parietal cells of the stomach. Other functions include absorbing some ions, water, and some lipid soluble compounds such as alcohol, aspirin, and caffeine. Another function of the stomach is simply a food storage cavity. # Anatomy of the human stomach The stomach lies between the esophagus and the duodenum (the first part of the small intestine). It is on the left side of the abdominal cavity. The top of the stomach lies against the diaphragm. Lying beneath the stomach is the pancreas, and the greater omentum which hangs from the greater curvature. Two smooth muscle valves, or sphincters, keep the contents of the stomach contained. They are the esophageal sphincter (found in the cardiac region) dividing the tract above, and the Pyloric sphincter dividing the stomach from the small intestine. The stomach is surrounded by parasympathetic (stimulant) and orthosympathetic (inhibitor) plexuses (anterior gastric, posterior, superior and inferior, celiac and myenteric), which regulate both the secretory activity and the motor activity of the muscles. In humans, the stomach has a volume of about 50 mL when empty. After a meal, it generally expands to hold about 1 litre of food, [1] but it can actually expand to hold as much as 4 litres. When drinking milk it can expand to just under 6 pints, or 3.4 litres. [2] ## Sections The stomach is divided into four sections, each of which has different cells and functions. The sections are: ## Blood supply The lesser curvature of the stomach is supplied by the right gastric artery inferiorly, and the left gastric artery superiorly, which also supplies the cardiac region. The greater curvature is supplied by the right gastroepiploic artery inferiorly and the left gastroepiploic artery superiorly. The fundus of the stomach, and also the upper portion of the greater curvature, are supplied by the short gastric artery # Histology of the human stomach ## Layers Like the other parts of the gastrointestinal tract, the stomach walls are made of the following layers, from inside to outside: ## Glands The epithelium of the stomach forms deep pits. The glands at these locations are named for the corresponding part of the stomach: Different types of cells are found at the different layers of these glands: # Control of secretion and motility The movement and the flow of chemicals into the stomach are controlled by both the autonomic nervous system and by the various digestive system hormones: Other than gastrin, these hormones all act to turn off the stomach action. This is in response to food products in the liver and gall bladder, which have not yet been absorbed. The stomach needs only to push food into the small intestine when the intestine is not busy. While the intestine is full and still digesting food, the stomach acts as storage for food. # Diseases of the stomach - Dyspepsia - Stomach ache - Peptic ulcer - Achlorhydria - Hypochlorhydria - Linitis plastica - Zollinger-Ellison syndrome - Gastroparesis - GERD - Borborygmus Historically, it was widely believed that the highly acidic environment of the stomach would keep the stomach immune from infection. However, a large number of studies have indicated that most cases of stomach ulcers, gastritis, and stomach cancer are caused by Helicobacter pylori infection. One of the ways it is able to survive in the stomach involves its urease enzymes which metabolize urea (which is normally secreted into the stomach) to ammonia and carbon dioxide which neutralizes gastric acid and thus prevents its digestion. In recent years, it has been discovered that other Helicobacter bacteria are also capable of colonizing the stomach and have been associated with gastritis. Having too little or no gastric acid is known as hypochlorhydria or achlorhydria respectively and are conditions which can have negative health impacts. Having high levels of gastric acid is called hyperchlorhydria. Many people believe that hyperchlorhydria can cause stomach ulcers. However, recent research indicates that the gastric mucosa which secretes gastric acid is acid-resistant. # Differences among animals In ruminants, such as bovines, the stomach is a large multichamber organ which hosts symbiotic bacteria that produce enzymes required for the digestion of cellulose from plant matter, primarily cellulase. The partially digested plant matter passes through each of the intestine chambers in sequence, being regurgitated and rechewed at least once in the process. In some animals (such as cats and dogs), the pH of the lumen is lower, usually between 1 and 2. In contrast, the human stomach pH is usually between 1 and 3.	https://www.wikidoc.org/index.php/Gastric
3915449c8803e7a62ee99fa89f9b7d5f7de3a555	wikidoc	Geminin	Geminin Geminin, DNA replication inhibitor, also known as GMNN, is a protein in humans encoded by the GMNN gene. Geminin is a nuclear protein that is present in most eukaryotics and highly conserved across species. Numerous functions have been elucidated for Geminin including roles in metazoan cell cycle, cellular proliferation, cell lineage commitment, and neural differentiation. # History Geminin was originally identified as an inhibitor of DNA replication and substrate of the anaphase promoting complex (APC). Coincidentally, geminin was also shown to expand the neural plate in the developing Xenopus embryo. # Structure Geminin is a nuclear protein made up of about 200 amino acids, with a molecular weight of approximately 25 kDa. It contains an atypical leucine-zipper coiled-coil domain. It has no known enzymatic activity nor DNA binding motifs. # Function ## Cell cycle control Geminin is absent during G1 phase and accumulates through S, G2 phase and M phases of the cell cycle. Geminin levels drop at the metaphase / anaphase transition of mitosis when it is degraded by the Anaphase Promoting Complex (APC/C). ### S phase During S phase, geminin is a negative regulator of DNA replication. In many cancer cell lines, inhibition of geminin by RNAi results in re-replication of portions of the genome, which leads to aneuploidy. In these cell lines, geminin knockdown leads to markedly slowed growth and apoptosis within several days. However, the same is not true for primary and immortalized human cell lines, where other mechanisms exists to prevent DNA re-replication. Since geminin knockdown leads to cell death in many cancer cell lines but not primary cell lines, it has been proposed as a potential therapeutic target for cancer treatment. ### Mitosis At the start of the S-phase until late mitosis, geminin inhibits the replication factor Cdt1, preventing the assembly of the pre-replicative complex. In early G1, the APC/C complex triggers its destruction through ubiquitination. Although inhibition of geminin by RNAi leads to impairment of DNA replication during the following cell cycle in many cancer cell lines, no such cell cycle defect is seen in primary and immortalized cell lines (although Cdt1 levels are still reduced in these cells). Geminin therefore is an important player in ensuring that one and only one round of replication occurs during each cell cycle. ## Developmental control Geminin promotes early neural fate commitment by hyperacetylating the chromatin. This effect allows neural genes to be accessible for transcription, promoting the expression of these genes. Ultimately, geminin allows cells uncommitted to any particular lineage to acquire neural characteristics. Geminin has also been shown to interact with the SWI/SNF chromatin remodeling complex. In neural precursor cells, high levels of geminin prevent terminal differentiation. When the interaction between geminin and SWI/SNF is eliminated, geminin's inhibition to this process is eliminated and neural precursors are allowed to differentiate. # Model organisms Model organisms have been used in the study of Geminin function. A conditional knockout mouse line, called Gmnntm1a(KOMP)Wtsi was generated as part of the International Knockout Mouse Consortium program, a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists. In addition, increased genomic instability and tumorigenesis have been observed in Geminin knockout mice in both the colon and lung. Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion. Twenty six tests were carried out and three significant abnormalities were observed. A recessive lethal study found no homozygous mutant embryos during gestation, and therefore none survived until weaning. The remaining tests were carried out on heterozygous mutant adult mice and showed that females had abnormal lens morphology and cataracts. # Clinical significance Geminin has been found to be overexpressed in several malignancies and cancer cell lines, while there is data demonstrating that Geminin acts as a tumor suppressor by safeguarding genome stability.	Geminin Geminin, DNA replication inhibitor, also known as GMNN, is a protein in humans encoded by the GMNN gene.[1] Geminin is a nuclear protein that is present in most eukaryotics and highly conserved across species. Numerous functions have been elucidated for Geminin including roles in metazoan cell cycle, cellular proliferation, cell lineage commitment, and neural differentiation.[2] # History Geminin was originally identified as an inhibitor of DNA replication and substrate of the anaphase promoting complex (APC).[3] Coincidentally, geminin was also shown to expand the neural plate in the developing Xenopus embryo.[4] # Structure Geminin is a nuclear protein made up of about 200 amino acids, with a molecular weight of approximately 25 kDa.[3] It contains an atypical leucine-zipper coiled-coil domain. It has no known enzymatic activity nor DNA binding motifs. # Function ## Cell cycle control Geminin is absent during G1 phase and accumulates through S, G2 phase and M phases of the cell cycle. Geminin levels drop at the metaphase / anaphase transition of mitosis when it is degraded by the Anaphase Promoting Complex (APC/C).[3] ### S phase During S phase, geminin is a negative regulator of DNA replication. In many cancer cell lines, inhibition of geminin by RNAi results in re-replication of portions of the genome, which leads to aneuploidy. In these cell lines, geminin knockdown leads to markedly slowed growth and apoptosis within several days.[5] However, the same is not true for primary and immortalized human cell lines, where other mechanisms exists to prevent DNA re-replication.[5] Since geminin knockdown leads to cell death in many cancer cell lines but not primary cell lines, it has been proposed as a potential therapeutic target for cancer treatment.[5] ### Mitosis At the start of the S-phase until late mitosis, geminin inhibits the replication factor Cdt1, preventing the assembly of the pre-replicative complex. In early G1, the APC/C complex triggers its destruction through ubiquitination. Although inhibition of geminin by RNAi leads to impairment of DNA replication during the following cell cycle in many cancer cell lines, no such cell cycle defect is seen in primary and immortalized cell lines (although Cdt1 levels are still reduced in these cells).[5] Geminin therefore is an important player in ensuring that one and only one round of replication occurs during each cell cycle. ## Developmental control Geminin promotes early neural fate commitment by hyperacetylating the chromatin.[6] This effect allows neural genes to be accessible for transcription, promoting the expression of these genes. Ultimately, geminin allows cells uncommitted to any particular lineage to acquire neural characteristics. Geminin has also been shown to interact with the SWI/SNF chromatin remodeling complex.[7] In neural precursor cells, high levels of geminin prevent terminal differentiation. When the interaction between geminin and SWI/SNF is eliminated, geminin's inhibition to this process is eliminated and neural precursors are allowed to differentiate. # Model organisms Model organisms have been used in the study of Geminin function. A conditional knockout mouse line, called Gmnntm1a(KOMP)Wtsi[13][14] 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.[15][16][17] In addition, increased genomic instability and tumorigenesis have been observed in Geminin knockout mice in both the colon and lung.[18] Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion.[11][19] Twenty six tests were carried out and three significant abnormalities were observed. A recessive lethal study found no homozygous mutant embryos during gestation, and therefore none survived until weaning. The remaining tests were carried out on heterozygous mutant adult mice and showed that females had abnormal lens morphology and cataracts.[11] # Clinical significance Geminin has been found to be overexpressed in several malignancies and cancer cell lines,[20] while there is data demonstrating that Geminin acts as a tumor suppressor by safeguarding genome stability.[18]	https://www.wikidoc.org/index.php/Geminin
aabc82f4bf943c5eece6265c1567f407cc3a7499	wikidoc	Genomes	Genomes The genome is the entirety of an organism's hereditary information. In humans, it is encoded in DNA. The genome includes both the genes and the non-coding sequences of the DNA. Genetic information is encoded as a sequence of nucleobases: adenine (A), cytosine (C), guanine (G), and thymine (T). There are "3.2 billion base pairs in the human genome." Associated with genomes are epigenomes. # Theoretical genomes Def. the "complete genetic information ... of an organism" is called a genome. # Genomics Genomics is a branch of molecular biology concerned with the structure, function, evolution, and mapping of genomes. The H (heavy, outer circle) and L (light, inner circle) strands are given with their corresponding genes. There are 22 transfer RNA (TRN) genes for the following amino acids: F, V, L1 (codon UUA/G), I, Q, M, W, A, N, C, Y, S1 (UCN), D, K, G, R, H, S2 (AGC/U), L2 (CUN), E, T and P (white boxes). There are 2 ribosomal RNA (RRN) genes: S (small subunit, or 12S) and L (large subunit, or 16S) (blue boxes). There are 13 protein-coding genes: 7 for NADH dehydrogenase subunits (ND, yellow boxes), 3 for cytochrome c oxidase subunits (COX, orange boxes), 2 for ATPase subunits (ATP, red boxes), and one for cytochrome b (CYTB, coral box). Two gene overlaps are indicated (ATP8-ATP6, and ND4L-ND4, black boxes). The control region (CR) is the longest non-coding sequence (grey box). Its three hyper-variable regions are indicated (HV, green boxes). # Epigenomes Inside each eukaryote nucleus is genetic material (DNA) surrounded by protective and regulatory proteins. These protective and regulatory proteins and the dynamic changes to them that occur during the course of a eukaryote's existence are the epigenome. An epigenome consists of a record of the chemical changes to the DNA and histone proteins of an organism that can be passed down to an organism's offspring via transgenerational epigenetic inheritance, where changes to the epigenome can result in changes to the structure of chromatin and changes to the function of the genome. Unlike the underlying genome which is largely static within an individual, the epigenome can be dynamically altered by environmental conditions. # Deoxyribonucleic acids Deoxyribonucleic acid (DNA) is composed of nucleobases (the sequence of which is the epigenome), deoxyribose (a sugar), and phosphate groups. Each nucleobase is attached to one deoxyribose molecule and one (PO4) phosphate molecule to form a chain of nucleotides (nucleobase + deoxyribose + phosphate) for a haploid genome. A linking of nucleobases may occur without the phosphate or the deoxyribose. The phosphate and the sugar are part of the epigenome. # Biochemistry A haploid genome contains non-repetitive DNA and repetitive DNA. Non-repetitive DNA consists mainly of coding DNA. In eukaryotes, the coding DNA consists of genes having exon-intron organization. The major part of mammalian genomes is repetitive DNA. In eukaryotes such as plants, protozoa and animals, however, "genome" carries the typical connotation of only information on chromosomal DNA. So although these organisms contain chloroplasts and/or mitochondria that have their own DNA, the genetic information contained by DNA within these organelles is not considered part of the genome. In fact, mitochondria are sometimes said to have their own genome often referred to as the "mitochondrial genome". The DNA found within the chloroplast may be referred to as the "plastome". Genetic information is encoded as a sequence of nucleobases: adenine (A), cytosine (C), guanine (G), and thymine (T). # Human DNA "uman DNA has millions of on-off switches and complex networks that control the genes' activities. ... t least 80% of the human genome is active, which opposed the previously held idea that most of the DNA are useless." "DNA contains genes, which hold the instructions for take up only about 2 percent of the genome ... The human genome is made up of about 3 billion “letters” along strands that make up the familiar double helix structure of DNA. Particular sequences of these letters form genes, which tell cells how to make proteins. People have about 20,000 genes, but the vast majority of DNA lies outside of genes. ... t least three-quarters of the genome is involved in making RNA it appears to help regulate gene activity." # Non-repetitive DNA Each gene has exons interspaced with introns, usually alternating along the DNA template strand. Before and after these are the 5' and 3' untranslated regions, by convention, respectively. Between genes usually before the gene in the direction of transcription are nucleotide sequences that contain the gene promoters. # Mitochondrial DNA Mitochondrial DNA (mtDNA) is a circular double strand molecule as in the image on the right which has a length of 15-20 kilobases in animals. In most species it has the same 37 genes that codify for 13 proteins, 2 ribosomal RNAs and 22 transfer RNAs. The human mtDNA was the first mitochondrial genome sequenced. This first complete sequence was called Cambridge Reference Sequence (CRS). This mtDNA is composed of 16,569 base pairs (bp) with their genes distributed between the H chain (high) and the L chain (light). With the exception of the Control Region (D-loop) which has regulatory functions and a 9 bp region called V Region, all the rest of the genome consists in coding DNA. In the last 30 years, the mtDNA has been widely used in human evolution studies as a consequence of its particular characteristics that make it an ideal and useful tool. Because of its non-coding nature, the Control Region exhibits the highest mutation rate in the mitochondrial genome. Several studies have demonstrated the strictly maternal inheritance of mtDNA, a phenomenon which represents an enormous advantage because it allows tracing related matrilineages along time without all inherent nuclear DNA problems like recombination and biparental inheritance. # Viral genomes Viral genomes can be composed of either RNA or DNA. The genomes of RNA viruses can be either single-stranded or double-stranded RNA], and may contain one or more separate RNA molecules. DNA viruses can have either single-stranded or double-stranded genomes. Most DNA virus genomes are composed of a single, linear molecule of DNA, but some are made up of a circular DNA molecule. # Archaea genomes Archaea have a single circular chromosome. # Prokaryotic genomes Most bacteria also have a single circular chromosome; however, some bacterial species have linear chromosomes or multiple chromosomes. If the DNA is replicated faster than the bacterial cells divide, multiple copies of the chromosome can be present in a single cell. Most prokaryotes have very little repetitive DNA in their genomes. However, some symbiotic bacteria (e.g. Serratia symbiotica) have reduced genomes and a high fraction of pseudogenes: only ~40% of their DNA encodes proteins. Some bacteria have auxiliary genetic material, which is carried in plasmids. # Eukaryotic genomes Eukaryotic genomes are composed of one or more linear DNA chromosomes. The number of chromosomes varies widely from Jack jumper ants and Diploscapter pachys an asexual nemotode, which each have only one pair, to an Ophioglossum or fern species that has 720 pairs. A typical human cell has two copies of each of 22 autosomes, one inherited from each parent, plus two sex chromosomes, making it diploid. Gametes, such as ova, sperm, spores, and pollen, are haploid, meaning they carry only one copy of each chromosome. In addition to the chromosomes in the nucleus, organelles such as the chloroplasts and mitochondria have their own DNA. Mitochondria are sometimes said to have their own genome often referred to as the "mitochondrial genome". The DNA found within the chloroplast may be referred to as the "plastome". Like the bacteria they originated from, mitochondria and chloroplasts have a circular chromosome. Unlike prokaryotes, eukaryotes have exon-intron organization of protein coding genes and variable amounts of repetitive DNA. In mammals and plants, the majority of the genome is composed of repetitive DNA. A larger genome does not necessarily contain more genes, and the proportion of non-repetitive DNA decreases along with increasing genome size in complex eukaryotes. Simple eukaryotes such as Caenorhabditis elegans and Drosophila melanogaster (fruit fly), have more non-repetitive DNA than repetitive DNA, while the genomes of more complex eukaryotes tend to be composed largely of repetitive DNA. In some plants and amphibians, the proportion of repetitive DNA is more than 80%. Similarly, only 2% of the human genome codes for proteins. ## Non-coding sequences Noncoding sequences include introns, sequences for non-coding RNAs, regulatory regions, and repetitive DNA. Noncoding sequences make up 98% of the human genome. There are two categories of repetitive DNA in the genome: tandem repeats and interspersed repeats. ## Tandem repeats Short, non-coding sequences that are repeated head-to-tail are called tandem repeats. Microsatellites consisting of 2-5 basepair repeats, while minisatellite repeats are 30-35 bp. Tandem repeats make up about 4% of the human genome and 9% of the fruit fly genome. Tandom repeats can be functional. For example, telomeres are composed of the tandem repeat TTAGGG in mammals, and they play an important role in protecting the ends of the chromosome. In other cases, expansions in the number of tandem repeats in exons or introns can cause disease. For example, the human gene huntingtin typically contains 6-29 tandem repeats of the nucleotides CAG (encoding a polyglutamine tract). An expansion to over 36 repeats results in Huntington's disease, a neurodegenerative disease. Twenty human disorders are known to result from similar tandem repeat expansions in various genes. The mechanism by which proteins with expanded polygulatamine tracts cause death of neurons is not fully understood. One possibility is that the proteins fail to fold properly and avoid degradation, instead accumulating in aggregates that also sequester important transcription factors, thereby altering gene expression. Tandem repeats are usually caused by slippage during replication, unequal crossing-over and gene conversion. ## Transposable elements Transposable elements (TEs) are sequences of DNA with a defined structure that are able to change their location in the genome. TEs are categorized as either class I TEs, which replicate by a copy-and-paste mechanism, or class II TEs, which can be excised from the genome and inserted at a new location. The movement of TEs is a driving force of genome evolution in eukaryotes because their insertion can disrupt gene functions, homologous recombination between TEs can produce duplications, and TE can shuffle exons and regulatory sequences to new locations. ## Retrotransposons Retrotransposons can be transcribed into RNA, which are then duplicated at another site into the genome. Retrotransposons can be divided into Long terminal repeats (LTRs) and Non-Long Terminal Repeats (Non-LTR). Long terminal repeats (LTRs) are derived from ancient retroviral infections, so they encode proteins related to retroviral proteins including gag (structural proteins of the virus), pol (reverse transcriptase and integrase), pro (protease), and in some cases env (envelope) genes. These genes are flanked by long repeats at both 5' and 3' ends. It has been reported that LTRs consist of the largest fraction in most plant genome and might account for the huge variation in genome size. Non-long terminal repeats (Non-LTRs) are classified as long interspersed elements (LINEs), short interspersed elements (SINEs), and Penelope-like elements. In Dictyostelium discoideum, there is another DIRS-like elements belong to Non-LTRs. Non-LTRs are widely spread in eukaryotic genomes. Long interspersed elements (LINEs) encode genes for reverse transcriptase and endonuclease, making them autonomous transposable elements. The human genome has around 500,000 LINEs, taking around 17% of the genome. Short interspersed elements (SINEs) are usually less than 500 base pairs and are non-autonomous, so they rely on the proteins encoded by LINEs for transposition. The Alu element is the most common SINE found in primates. It is about 350 base pairs and occupies about 11% of the human genome with around 1,500,000 copies. ## DNA transposons DNA transposons encode a transposase enzyme between inverted terminal repeats, which when expressed, recognizes the terminal inverted repeats that flank the transposon and catalyzes its excision and reinsertion in a new site. This cut-and-paste mechanism typically reinserts transposons near their original location (within 100kb). DNA transposons are found in bacteria and make up 3% of the human genome and 12% of the genome of the roundworm C. elegans. # Hypotheses - The human genome may be less than 10 % human. # Acknowledgements The content on this page was first contributed by: Henry A. Hoff. Initial content for this page in some instances came from Wikiversity.	Genomes Editor-In-Chief: Henry A. Hoff Template:TOCright The genome is the entirety of an organism's hereditary information. In humans, it is encoded in DNA. The genome includes both the genes and the non-coding sequences of the DNA.[1] Genetic information is encoded as a sequence of nucleobases: adenine (A), cytosine (C), guanine (G), and thymine (T). There are "3.2 billion base pairs in the human genome."[2] Associated with genomes are epigenomes. # Theoretical genomes Def. the "complete genetic information ... of an organism"[3] is called a genome. # Genomics Genomics is a branch of molecular biology concerned with the structure, function, evolution, and mapping of genomes. The H (heavy, outer circle) and L (light, inner circle) strands are given with their corresponding genes. There are 22 transfer RNA (TRN) genes for the following amino acids: F, V, L1 (codon UUA/G), I, Q, M, W, A, N, C, Y, S1 (UCN), D, K, G, R, H, S2 (AGC/U), L2 (CUN), E, T and P (white boxes). There are 2 ribosomal RNA (RRN) genes: S (small subunit, or 12S) and L (large subunit, or 16S) (blue boxes). There are 13 protein-coding genes: 7 for NADH dehydrogenase subunits (ND, yellow boxes), 3 for cytochrome c oxidase subunits (COX, orange boxes), 2 for ATPase subunits (ATP, red boxes), and one for cytochrome b (CYTB, coral box). Two gene overlaps are indicated (ATP8-ATP6, and ND4L-ND4, black boxes). The control region (CR) is the longest non-coding sequence (grey box). Its three hyper-variable regions are indicated (HV, green boxes). # Epigenomes Inside each eukaryote nucleus is genetic material (DNA) surrounded by protective and regulatory proteins. These protective and regulatory proteins and the dynamic changes to them that occur during the course of a eukaryote's existence are the epigenome. An epigenome consists of a record of the chemical changes to the DNA and histone proteins of an organism that can be passed down to an organism's offspring via transgenerational epigenetic inheritance, where changes to the epigenome can result in changes to the structure of chromatin and changes to the function of the genome.[4] Unlike the underlying genome which is largely static within an individual, the epigenome can be dynamically altered by environmental conditions.[5] # Deoxyribonucleic acids Deoxyribonucleic acid (DNA) is composed of nucleobases (the sequence of which is the epigenome), deoxyribose (a sugar), and phosphate groups. Each nucleobase is attached to one deoxyribose molecule and one (PO4) phosphate molecule to form a chain of nucleotides (nucleobase + deoxyribose + phosphate) for a haploid genome. A linking of nucleobases may occur without the phosphate or the deoxyribose. The phosphate and the sugar are part of the epigenome. # Biochemistry A haploid genome contains non-repetitive DNA and repetitive DNA. Non-repetitive DNA consists mainly of coding DNA. In eukaryotes, the coding DNA consists of genes having exon-intron organization. The major part of mammalian genomes is repetitive DNA.[6] In eukaryotes such as plants, protozoa and animals, however, "genome" carries the typical connotation of only information on chromosomal DNA. So although these organisms contain chloroplasts and/or mitochondria that have their own DNA, the genetic information contained by DNA within these organelles is not considered part of the genome. In fact, mitochondria are sometimes said to have their own genome often referred to as the "mitochondrial genome". The DNA found within the chloroplast may be referred to as the "plastome". Genetic information is encoded as a sequence of nucleobases: adenine (A), cytosine (C), guanine (G), and thymine (T). # Human DNA "[H]uman DNA has millions of on-off switches and complex networks that control the genes' activities. ... [A]t least 80% of the human genome is active, which opposed the previously held idea that most of the DNA are useless."[7] "DNA contains genes, which hold the instructions for [life. But, these] take up only about 2 percent of the genome ... The human genome is made up of about 3 billion “letters” along strands that make up the familiar double helix structure of DNA. Particular sequences of these letters form genes, which tell cells how to make proteins. People have about 20,000 genes, but the vast majority of DNA lies outside of genes. ... [A]t least three-quarters of the genome is involved in making RNA [...] it appears to help regulate gene activity."[8] # Non-repetitive DNA Each gene has exons interspaced with introns, usually alternating along the DNA template strand. Before and after these are the 5' and 3' untranslated regions, by convention, respectively. Between genes usually before the gene in the direction of transcription are nucleotide sequences that contain the gene promoters. # Mitochondrial DNA Mitochondrial DNA (mtDNA) is a circular double strand molecule as in the image on the right which has a length of 15-20 kilobases in animals. In most species it has the same 37 genes that codify for 13 proteins, 2 ribosomal RNAs and 22 transfer RNAs. The human mtDNA was the first mitochondrial genome sequenced. This first complete sequence was called Cambridge Reference Sequence (CRS). This mtDNA is composed of 16,569 base pairs (bp) with their genes distributed between the H chain (high) and the L chain (light). With the exception of the Control Region (D-loop) which has regulatory functions and a 9 bp region called V Region, all the rest of the genome consists in coding DNA. In the last 30 years, the mtDNA has been widely used in human evolution studies as a consequence of its particular characteristics that make it an ideal and useful tool. Because of its non-coding nature, the Control Region exhibits the highest mutation rate in the mitochondrial genome. Several studies have demonstrated the strictly maternal inheritance of mtDNA, a phenomenon which represents an enormous advantage because it allows tracing related matrilineages along time without all inherent nuclear DNA problems like recombination and biparental inheritance.[9] # Viral genomes Viral genomes can be composed of either RNA or DNA. The genomes of RNA viruses can be either single-stranded or double-stranded RNA], and may contain one or more separate RNA molecules. DNA viruses can have either single-stranded or double-stranded genomes. Most DNA virus genomes are composed of a single, linear molecule of DNA, but some are made up of a circular DNA molecule.[10] # Archaea genomes Archaea have a single circular chromosome.[11] # Prokaryotic genomes Most bacteria also have a single circular chromosome; however, some bacterial species have linear chromosomes[12] or multiple chromosomes.[13] If the DNA is replicated faster than the bacterial cells divide, multiple copies of the chromosome can be present in a single cell. Most prokaryotes have very little repetitive DNA in their genomes.[14] However, some symbiotic bacteria (e.g. Serratia symbiotica) have reduced genomes and a high fraction of pseudogenes: only ~40% of their DNA encodes proteins.[15][16] Some bacteria have auxiliary genetic material, which is carried in plasmids. # Eukaryotic genomes Eukaryotic genomes are composed of one or more linear DNA chromosomes. The number of chromosomes varies widely from Jack jumper ants and Diploscapter pachys an asexual nemotode,[17] which each have only one pair, to an Ophioglossum or fern species that has 720 pairs.[18] A typical human cell has two copies of each of 22 autosomes, one inherited from each parent, plus two sex chromosomes, making it diploid. Gametes, such as ova, sperm, spores, and pollen, are haploid, meaning they carry only one copy of each chromosome. In addition to the chromosomes in the nucleus, organelles such as the chloroplasts and mitochondria have their own DNA. Mitochondria are sometimes said to have their own genome often referred to as the "mitochondrial genome". The DNA found within the chloroplast may be referred to as the "plastome". Like the bacteria they originated from, mitochondria and chloroplasts have a circular chromosome. Unlike prokaryotes, eukaryotes have exon-intron organization of protein coding genes and variable amounts of repetitive DNA. In mammals and plants, the majority of the genome is composed of repetitive DNA.[19] A larger genome does not necessarily contain more genes, and the proportion of non-repetitive DNA decreases along with increasing genome size in complex eukaryotes.[19] Simple eukaryotes such as Caenorhabditis elegans and Drosophila melanogaster (fruit fly), have more non-repetitive DNA than repetitive DNA,[19][20] while the genomes of more complex eukaryotes tend to be composed largely of repetitive DNA.[21] In some plants and amphibians, the proportion of repetitive DNA is more than 80%.[19] Similarly, only 2% of the human genome codes for proteins. ## Non-coding sequences Noncoding sequences include introns, sequences for non-coding RNAs, regulatory regions, and repetitive DNA. Noncoding sequences make up 98% of the human genome. There are two categories of repetitive DNA in the genome: tandem repeats and interspersed repeats.[22] ## Tandem repeats Short, non-coding sequences that are repeated head-to-tail are called tandem repeats. Microsatellites consisting of 2-5 basepair repeats, while minisatellite repeats are 30-35 bp. Tandem repeats make up about 4% of the human genome and 9% of the fruit fly genome.[23] Tandom repeats can be functional. For example, telomeres are composed of the tandem repeat TTAGGG in mammals, and they play an important role in protecting the ends of the chromosome. In other cases, expansions in the number of tandem repeats in exons or introns can cause disease.[24] For example, the human gene huntingtin typically contains 6-29 tandem repeats of the nucleotides CAG (encoding a polyglutamine tract). An expansion to over 36 repeats results in Huntington's disease, a neurodegenerative disease. Twenty human disorders are known to result from similar tandem repeat expansions in various genes. The mechanism by which proteins with expanded polygulatamine tracts cause death of neurons is not fully understood. One possibility is that the proteins fail to fold properly and avoid degradation, instead accumulating in aggregates that also sequester important transcription factors, thereby altering gene expression.[24] Tandem repeats are usually caused by slippage during replication, unequal crossing-over and gene conversion.[25] ## Transposable elements Transposable elements (TEs) are sequences of DNA with a defined structure that are able to change their location in the genome.[23][14][26] TEs are categorized as either class I TEs, which replicate by a copy-and-paste mechanism, or class II TEs, which can be excised from the genome and inserted at a new location. The movement of TEs is a driving force of genome evolution in eukaryotes because their insertion can disrupt gene functions, homologous recombination between TEs can produce duplications, and TE can shuffle exons and regulatory sequences to new locations.[27] ## Retrotransposons Retrotransposons can be transcribed into RNA, which are then duplicated at another site into the genome.[28] Retrotransposons can be divided into Long terminal repeats (LTRs) and Non-Long Terminal Repeats (Non-LTR).[27] Long terminal repeats (LTRs) are derived from ancient retroviral infections, so they encode proteins related to retroviral proteins including gag (structural proteins of the virus), pol (reverse transcriptase and integrase), pro (protease), and in some cases env (envelope) genes.[26] These genes are flanked by long repeats at both 5' and 3' ends. It has been reported that LTRs consist of the largest fraction in most plant genome and might account for the huge variation in genome size.[29] Non-long terminal repeats (Non-LTRs) are classified as long interspersed elements (LINEs), short interspersed elements (SINEs), and Penelope-like elements. In Dictyostelium discoideum, there is another DIRS-like elements belong to Non-LTRs. Non-LTRs are widely spread in eukaryotic genomes.[30] Long interspersed elements (LINEs) encode genes for reverse transcriptase and endonuclease, making them autonomous transposable elements. The human genome has around 500,000 LINEs, taking around 17% of the genome.[31] Short interspersed elements (SINEs) are usually less than 500 base pairs and are non-autonomous, so they rely on the proteins encoded by LINEs for transposition.[32] The Alu element is the most common SINE found in primates. It is about 350 base pairs and occupies about 11% of the human genome with around 1,500,000 copies.[27] ## DNA transposons DNA transposons encode a transposase enzyme between inverted terminal repeats, which when expressed, recognizes the terminal inverted repeats that flank the transposon and catalyzes its excision and reinsertion in a new site.[23] This cut-and-paste mechanism typically reinserts transposons near their original location (within 100kb).[27] DNA transposons are found in bacteria and make up 3% of the human genome and 12% of the genome of the roundworm C. elegans.[27] # Hypotheses - The human genome may be less than 10 % human. # Acknowledgements The content on this page was first contributed by: Henry A. Hoff. Initial content for this page in some instances came from Wikiversity.	https://www.wikidoc.org/index.php/Genomes
317cd0a6d5539592b621e7080512d7a34aba5b1f	wikidoc	Gentian	Gentian Gentiana is a genus of flowering plants belonging to the Gentian family (Gentianaceae), tribe Gentianeae and monophyletic subtribe Gentianinae. This a large genus, with about 400 species. This is a cosmopolitan genus, occurring in alpine habitats of temperate regions of Asia, Europe and the Americas. Some species also occur in northwest Africa, eastern Australia and New Zealand. They consist of annual, biennial and perennial plants. Some are evergreen, others are not. Their leaves are arranged in an opposite way. Most of them belong to a basal rosette. Gentians have trumpet-shaped flowers which are usually deep blue or azure, but may vary from white, creamy and yellow to red. Blue-flowered species predominate in the Northern Hemisphere, and red in the Andes; white-flowered species are scattered but dominate in New Zealand. These terminal tubular flowers are mostly pentamerous, i.e. with 5 corolla lobes (petals), and 5 sepals, but 4-7 in some species. The style is rather short or absent. The corolla shows folds (= plicae) between the lobes. The ovary is mostly sessile and has nectary glands. Gentians are fully hardy and like full sun or partial shade, and neutral to acid soil that is rich in humus and well drained. They are popular in rock gardens. According to Pliny the Elder, Gentian is an eponym of Gentius (180-168 BC), the King of Illyria, said to have discovered its healing properties. Some species are of medicinal use and their roots were harvested for the manufacture of tonic liquor, for instance in France "Suze" or similar liquors. Gentian is also used as a flavouring, for example in bitters, and the soft drink "Moxie" which contains "Gentian Root Extractives". # Species	Gentian Gentiana is a genus of flowering plants belonging to the Gentian family (Gentianaceae), tribe Gentianeae and monophyletic subtribe Gentianinae. This a large genus, with about 400 species. This is a cosmopolitan genus, occurring in alpine habitats of temperate regions of Asia, Europe and the Americas. Some species also occur in northwest Africa, eastern Australia and New Zealand. They consist of annual, biennial and perennial plants. Some are evergreen, others are not. Their leaves are arranged in an opposite way. Most of them belong to a basal rosette. Gentians have trumpet-shaped flowers which are usually deep blue or azure, but may vary from white, creamy and yellow to red. Blue-flowered species predominate in the Northern Hemisphere, and red in the Andes; white-flowered species are scattered but dominate in New Zealand. These terminal tubular flowers are mostly pentamerous, i.e. with 5 corolla lobes (petals), and 5 sepals, but 4-7 in some species. The style is rather short or absent. The corolla shows folds (= plicae) between the lobes. The ovary is mostly sessile and has nectary glands. Gentians are fully hardy and like full sun or partial shade, and neutral to acid soil that is rich in humus and well drained. They are popular in rock gardens. According to Pliny the Elder, Gentian is an eponym of Gentius (180-168 BC), the King of Illyria, said to have discovered its healing properties. Some species are of medicinal use and their roots were harvested for the manufacture of tonic liquor, for instance in France "Suze" or similar liquors. Gentian is also used as a flavouring, for example in bitters, and the soft drink "Moxie" which contains "Gentian Root Extractives". # Species	https://www.wikidoc.org/index.php/Gentian
e7894ccf92157aaf24ddec4e83ea11d757695c42	wikidoc	Genzyme	Genzyme Genzyme Corporation is a biotechnology company based in Cambridge, Massachusetts. Genzyme is the world’s third biggest biotechnology company employing over 9,000 people around the world. At present, the company has approximately 80 locations in 40 countries. It includes 17 manufacturing facilities and 9 genetic testing laboratories. The company’s products are available in nearly 90 countries. In 2006, Genzyme generated $3.2 billion in revenues with more than 25 products in the world’s markets. The company is also involved in philanthropic acts, donating $83 million in global product donations and $11 million in cash contributions in 2006. In 2006 and 2007 Genzyme was named one of Fortune Magazine’s “100 Best Companies to Work for.” Additionally in 2007, Genzyme was awarded the National Medal of Technology, the highest level of honor awarded by the President of the United States to America’s leading innovators. The company, started by a small group of scientists in 1981, was primarily devoted to finding drugs that would cure enzyme deficiency conditions that were essential to one’s survival and which usually afflict a very small percentage of the world’s population. Drugs used to treat such conditions are termed “orphan drugs.” In 1986, the company went public raising $27 million. Genzyme focuses on six areas of medicine relating to lysosomal storage diseases, renal disease, orthopedics, transplant and immune diseases, oncology, genetics and diagnostics. The first orphan-drug for Genzyme that FDA approved was Ceredase, a drug for treating Gaucher disease. Other important drugs made by Genzyme are Renagel, used in treatment of dialysis patients, and Fabrazyme, used to treat patients with Fabry's disease. Other products in development are Tolevamer for Clostridium dificile colitis disease and Campath for multiple sclerosis. Genzyme has a sub-license from Bioenvision to market Clofarabine in North America. Bioenvision has the rights to Clofarabine in the rest of the world. On Tuesday, May 29, 2007 Genzyme made a tender offer to purchase Bioenvision for $5.60 per share. Bioenvision management and the board of directors tendered their shares via an agreement prior to the announcement. However, not many other shareholders did and the tender offer closed without Genzyme acquiring their necessary 51% of Bioenvision. It remains to be seen if Genzyme will just be a shareholder of Bioenvision or proceed with a higher subsequent offer. In 2006, CEO, President, and Board Chairman Henri Termeer, earned a salary of $1.4 million, and non-cash compensation worth $21 million. # Product Listing Cerezyme® Fabrazyme® Aldurazyme® Myozyme® Renagel® Hectorol® Synvisc® Carticel® Thymol Globulin® Campath® Clolar® Thyrogen® Sepra® family of products Epicel®	Genzyme Template:Infobox Company Genzyme Corporation is a biotechnology company based in Cambridge, Massachusetts. Genzyme is the world’s third biggest biotechnology company employing over 9,000 people around the world. At present, the company has approximately 80 locations in 40 countries. It includes 17 manufacturing facilities and 9 genetic testing laboratories. The company’s products are available in nearly 90 countries. In 2006, Genzyme generated $3.2 billion in revenues with more than 25 products in the world’s markets. The company is also involved in philanthropic acts, donating $83 million in global product donations and $11 million in cash contributions in 2006. In 2006 and 2007 Genzyme was named one of Fortune Magazine’s “100 Best Companies to Work for.” Additionally in 2007, Genzyme was awarded the National Medal of Technology, the highest level of honor awarded by the President of the United States to America’s leading innovators. The company, started by a small group of scientists in 1981, was primarily devoted to finding drugs that would cure enzyme deficiency conditions that were essential to one’s survival and which usually afflict a very small percentage of the world’s population. Drugs used to treat such conditions are termed “orphan drugs.” In 1986, the company went public raising $27 million. Genzyme focuses on six areas of medicine relating to lysosomal storage diseases, renal disease, orthopedics, transplant and immune diseases, oncology, genetics and diagnostics. The first orphan-drug for Genzyme that FDA approved was Ceredase, a drug for treating Gaucher disease. Other important drugs made by Genzyme are Renagel, used in treatment of dialysis patients, and Fabrazyme, used to treat patients with Fabry's disease. Other products in development are Tolevamer for Clostridium dificile colitis disease and Campath for multiple sclerosis. Genzyme has a sub-license from Bioenvision to market Clofarabine in North America. Bioenvision has the rights to Clofarabine in the rest of the world. On Tuesday, May 29, 2007 Genzyme made a tender offer to purchase Bioenvision for $5.60 per share. Bioenvision management and the board of directors tendered their shares via an agreement prior to the announcement. However, not many other shareholders did and the tender offer closed without Genzyme acquiring their necessary 51% of Bioenvision. It remains to be seen if Genzyme will just be a shareholder of Bioenvision or proceed with a higher subsequent offer. In 2006, CEO, President, and Board Chairman Henri Termeer, earned a salary of $1.4 million, and non-cash compensation worth $21 million.[1] # Product Listing Cerezyme® Fabrazyme® Aldurazyme® Myozyme® Renagel® Hectorol® Synvisc® Carticel® Thymol Globulin® Campath® Clolar® Thyrogen® Sepra® family of products Epicel®	https://www.wikidoc.org/index.php/Genzyme
4052602c089e14a684285ebf9bb60b89753ed41e	wikidoc	Geology	Geology Geology (from Greek γη- (ge-, "the earth") and λογος (logos, "word", "reason")) is the science and study of the Earth, its make-up, structure, physical properties, history, and the processes that shape it. Geologists have helped establish the age of the Earth at about 4.5 billion (4.5x109) years, and that tectonic plates move over a viscous mantle to form the earth's crust. Geologists help locate and manage the earth's natural resources, such as oil. Astrogeology refers to the application of geologic principles to other bodies of the solar system. However, specialised terms such as selenology (studies of the Moon), areology (of Mars), etc., are also in use. The word was first used by Jean-André Deluc (1727 - 1817) in the year 1778 and introduced by Horace-Bénédict de Saussure (1740 - 1799) in the year 1779 as a fixed term. # History Georg Agricola (1494-1555) wrote the first systematic treatise about mining and smelting works, De re metallica libri XII, with an appendix Buch von den Lebewesen unter Tage (book of the creatures beneath the earth). He covered subjects like wind energy, hydrodynamic power, melting cookers, transport of ores, extraction of soda, sulfur and alum, and administrative issues. The book was published in 1556. James Hutton is often viewed as the first modern geologist. In 1785 he presented a paper entitled Theory of the Earth to the Royal Society of Edinburgh. In his paper, he explained his theory that the Earth must be much older than had previously been supposed, in order to allow enough time for mountains to be eroded, and for the sediment to form new rocks at the bottom of the sea, which were then raised up to dry land. Followers of Hutton were known as plutonists because they believed that some rocks were formed by vulcanism which is the deposition of lava from volcanoes, as opposed to the neptunists, who believed that all rocks had settled out of a large ocean whose level gradually dropped over time. William Smith (1769-1839) drew some of the first geological maps and began the process of ordering rock strata (layers) by examining the fossils contained in them. Sir Charles Lyell first published his famous book, Principles of Geology, in 1830 and continued to publish new revisions until he died in 1875. He successfully promoted the doctrine of uniformitarianism. This theory states that slow geological processes occurred throughout the earth's history, and are still occurring today. In contrast, catastrophism is the theory that Earth's features formed in single, catastrophic events and remained unchanged thereafter. (Hutton believed in uniformitarianism, but the idea was not widely accepted at the time.) The theory of continental drift was proposed by Alfred Wegener in 1912 and by Arthur Holmes, but wasn't broadly accepted until the 1960s when the theory of plate tectonics was developed. See also: Timeline of geology # Fields or Sub-disciplines - economic geology - environmental geology - geochemistry - geochronology - geodetics - geomicrobiology - geomorphology - geophysics - glaciology - hydrogeology or geohydrology - marine geology - mineralogy - paleoclimatology - paleontology - pedology (soil study) - petroleum geology - petrology - sedimentology - seismology - stratigraphy - structural geology - tectonics - volcanology There is also engineering geology, which supports civil engineering, especially geotechnical engineering, and geological engineering. The difference between geological engineering and engineering geology is real: geological engineers are licensed as engineers, engineering geologists are licensed as geologists. # Regional Geology - Geology of the Alps - Genesee River: Glacial Geology (New York, Pennsylvania) # National Geology - Geology of Australia Geology of Victoria - Geology of Victoria - Geology of the United States of America Geology of California Geology of the Grand Canyon area - Geology of California - Geology of the Grand Canyon area - Geology of the United Kingdom	Geology Geology (from Greek γη- (ge-, "the earth") and λογος (logos, "word", "reason")) is the science and study of the Earth, its make-up, structure, physical properties, history, and the processes that shape it. Geologists have helped establish the age of the Earth at about 4.5 billion (4.5x109) years, and that tectonic plates move over a viscous mantle to form the earth's crust. Geologists help locate and manage the earth's natural resources, such as oil. Astrogeology refers to the application of geologic principles to other bodies of the solar system. However, specialised terms such as selenology (studies of the Moon), areology (of Mars), etc., are also in use. The word was first used by Jean-André Deluc (1727 - 1817) in the year 1778 and introduced by Horace-Bénédict de Saussure (1740 - 1799) in the year 1779 as a fixed term. [An older meaning of the word is first used by Richard de Bury (1286 - 1345). He used it to distinguish between earthly and theological jurisprudence.] # History Georg Agricola (1494-1555) wrote the first systematic treatise about mining and smelting works, De re metallica libri XII, with an appendix Buch von den Lebewesen unter Tage (book of the creatures beneath the earth). He covered subjects like wind energy, hydrodynamic power, melting cookers, transport of ores, extraction of soda, sulfur and alum, and administrative issues. The book was published in 1556. James Hutton is often viewed as the first modern geologist. In 1785 he presented a paper entitled Theory of the Earth to the Royal Society of Edinburgh. In his paper, he explained his theory that the Earth must be much older than had previously been supposed, in order to allow enough time for mountains to be eroded, and for the sediment to form new rocks at the bottom of the sea, which were then raised up to dry land. Followers of Hutton were known as plutonists because they believed that some rocks were formed by vulcanism which is the deposition of lava from volcanoes, as opposed to the neptunists, who believed that all rocks had settled out of a large ocean whose level gradually dropped over time. William Smith (1769-1839) drew some of the first geological maps and began the process of ordering rock strata (layers) by examining the fossils contained in them. Sir Charles Lyell first published his famous book, Principles of Geology, in 1830 and continued to publish new revisions until he died in 1875. He successfully promoted the doctrine of uniformitarianism. This theory states that slow geological processes occurred throughout the earth's history, and are still occurring today. In contrast, catastrophism is the theory that Earth's features formed in single, catastrophic events and remained unchanged thereafter. (Hutton believed in uniformitarianism, but the idea was not widely accepted at the time.) The theory of continental drift was proposed by Alfred Wegener in 1912 and by Arthur Holmes, but wasn't broadly accepted until the 1960s when the theory of plate tectonics was developed. See also: Timeline of geology # Fields or Sub-disciplines - economic geology - environmental geology - geochemistry - geochronology - geodetics - geomicrobiology - geomorphology - geophysics - glaciology - hydrogeology or geohydrology - marine geology - mineralogy - paleoclimatology - paleontology - pedology (soil study) - petroleum geology - petrology - sedimentology - seismology - stratigraphy - structural geology - tectonics - volcanology There is also engineering geology, which supports civil engineering, especially geotechnical engineering, and geological engineering. The difference between geological engineering and engineering geology is real: geological engineers are licensed as engineers, engineering geologists are licensed as geologists. # Regional Geology - Geology of the Alps - Genesee River: Glacial Geology (New York, Pennsylvania) # National Geology - Geology of Australia Geology of Victoria - Geology of Victoria - Geology of the United States of America Geology of California Geology of the Grand Canyon area - Geology of California - Geology of the Grand Canyon area - Geology of the United Kingdom	https://www.wikidoc.org/index.php/Geology
1fc29159fac8052431b30218ce5541a1de4dec35	wikidoc	Gestalt	Gestalt Die Gestalt is a German word for form or shape. It is used in English to refer to a concept of 'wholeness' (see wiktionary). Gestalt may also refer to: - Gestalt psychology (or Gestalt theory), a theory of mind and brain, describing the Gestalt effect. - Gestalt Theoretical Psychotherapy, a method of psychotherapy based on Gestalt psychology - Gestalt therapy, a form of psychotherapy built on the experiential ideal of "here and now" and relationships with others and the world. - Gestalt (Mac OS), an environment-query function in Mac OS. - Gestalt (manga), an anime manga and OVA series ar:غيشتالت de:Gestalt nl:Gestalt sv:Gestalt	Gestalt Template:Wiktionarypar Die Gestalt is a German word for form or shape. It is used in English to refer to a concept of 'wholeness' (see wiktionary). Gestalt may also refer to: - Gestalt psychology (or Gestalt theory), a theory of mind and brain, describing the Gestalt effect. - Gestalt Theoretical Psychotherapy, a method of psychotherapy based on Gestalt psychology - Gestalt therapy, a form of psychotherapy built on the experiential ideal of "here and now" and relationships with others and the world. - Gestalt (Mac OS), an environment-query function in Mac OS. - Gestalt (manga), an anime manga and OVA series Template:Disambig ar:غيشتالت de:Gestalt nl:Gestalt sv:Gestalt Template:WS	https://www.wikidoc.org/index.php/Gestalt
b18379218522db4cbb326831b9fab6f6def46d93	wikidoc	Ghrelin	Ghrelin Ghrelin (pronounced /ˈɡrɛlɪn/), the "hunger hormone", also known as lenomorelin (INN), is a peptide hormone produced by ghrelinergic cells in the gastrointestinal tract that functions as a neuropeptide in the central nervous system. Besides regulating appetite, ghrelin also plays a significant role in regulating the distribution and rate of use of energy. When the stomach is empty, ghrelin is secreted. When the stomach is stretched, secretion stops.a It acts on hypothalamic brain cells both to increase hunger, and to increase gastric acid secretion and gastrointestinal motility to prepare the body for food intake. The receptor for ghrelin, the ghrelin/growth hormone secretagogue receptor (GHS-R), is found on the same cells in the brain as the receptor for leptin, the satiety hormone that has opposite effects from ghrelin. Ghrelin also plays an important role in regulating reward perception in dopamine neurons that link the ventral tegmental area to the nucleus accumbens (a site that plays a role in processing sexual desire, reward, and reinforcement, and in developing addictions) through its colocalized receptors and interaction with dopamine and acetylcholine. Ghrelin is encoded by the GHRL gene and is presumably produced from the cleavage of the prepropeptide ghrelin/obestatin. Full-length preproghrelin is homologous to promotilin and both are members of the motilin family. Unlike the case of many other endogenous peptides, ghrelin is able to cross the blood-brain-barrier, giving exogenously-administered ghrelin unique clinical potential. # History and name Ghrelin was discovered after the ghrelin receptor (called growth hormone secretagogue type 1A receptor or GHS-R) was discovered in 1996 and was reported in 1999. The hormone name is based on its role as a growth hormone-releasing peptide, with reference to the Proto-Indo-European root gʰre-, meaning "to grow". # Gene, transcription products, and structure The GHRL gene produces mRNA which has four exons. Five products arise: the first is the 117-amino acid preproghrelin. (It is homologous to promotilin; both are members of the motilin family). It is cleaved to produce proghrelin which is cleaved to produce a 28-amino acid ghrelin (unacylated) and C-ghrelin(acylated). Obestatin is presumed to be cleaved from C-ghrelin. Ghrelin only becomes active when caprylic (octanoic) acid is linked posttranslationally to serine at the 3-position by the enzyme ghrelin O-acyltransferase (GOAT). It is located on the cell membrane of ghrelin cells in the stomach and pancreas. The non-octanoylated form is desacyl ghrelin. It does not activate the GHS-R receptor but does have other effects: cardiac, anti-ghrelin, appetite stimulation, and inhibition of hepatic glucose output Side-chains other than octanoyl have also been observed: these can also trigger the ghrelin receptor. In particular, decanoyl ghrelin has been found to constitute a significant portion of circulating ghrelin in mice, but as of 2011 its presence in humans has not been established. # Ghrelin cells ## Alternative names The ghrelin cell is also known as an A-like cell (pancreas), X-cell (for unknown function), X/A-like cell (rats), Epsilon cell (pancreas), P/D sub 1 cell (humans) and Gr cell (abbreviation for ghrelin cell). ## Location Ghrelin cells are found mainly in the stomach and duodenum, but also in the jejunum, lungs, pancreatic islets, gonads, adrenal cortex, placenta, and kidney. It has recently been shown that ghrelin is produced locally in the brain ## Features Ghrelin cells are found in oxyntic glands (20% of cells), pyloric glands, and small intestine. They are ovoid cells with granules. They have gastrin receptors. Some produce nesfatin-1. Ghrelin cells are not terminally differentiated in the pancreas: they are progenitor cells that can give rise to A-cells, PP cells and Beta-cells there. # Function and mechanism of action Ghrelin is a participant in regulating the complex process of energy homeostasis which adjusts both energy input – by adjusting hunger signals – and energy output – by adjusting the proportion of energy going to ATP production, fat storage, glycogen storage, and short-term heat loss. The net result of these processes is reflected in body weight, and is under continuous monitoring and adjustment based on metabolic signals and needs. At any given moment in time, it may be in equilibrium or disequilibrium. Gastric-brain communication is an essential part of energy homeostasis, and several communication pathways are probable, including the gastric intracellular mTOR/S6K1 pathway mediating the interaction among ghrelin, nesfatin and endocannabinoid gastric systems, and both afferent and efferent vagal signals. Ghrelin and synthetic ghrelin mimetics (growth hormone secretagogues) increase body weight and fat mass by triggering receptors in the arcuate nucleus that include the orexigenic neuropeptide Y (NPY) and agouti-related protein (AgRP) neurons. Ghrelin-responsiveness of these neurons is both leptin- and insulin-sensitive. Ghrelin reduces the mechanosensitivity of gastric vagal afferents, so they are less sensitive to gastric distension. In addition to its function in energy homeostasis, ghrelin also activates the cholinergic–dopaminergic reward link in inputs to the ventral tegmental area and in the mesolimbic pathway, a circuit that communicates the hedonic and reinforcing aspects of natural rewards, such as food and addictive drugs such as ethanol. Ghrelin receptors are located on neurons in this circuit. Hypothalamic ghrelin signalling is required for reward from alcohol and palatable/rewarding foods. Ghrelin has been linked to inducing appetite and feeding behaviors. Circulating ghrelin levels are the highest right before a meal and the lowest right after. Injections of ghrelin in both humans and rats have been shown to increase food intake in a dose-dependent manner. So the more ghrelin that is injected the more food that is consumed. However, ghrelin does not increase meal size, only meal number. Ghrelin injections also increase an animal's motivation to seek out food, behaviors including increased sniffing, foraging for food, and hoarding food. Body weight is regulated through energy balance, the amount of energy taken in versus the amount of energy expended over an extended period of time. Studies have shown that ghrelin levels are negatively correlated with weight. This data suggests that ghrelin functions as an adiposity signal, a messenger between the body's energy stores and the brain. # Blood levels Blood levels are in the pmol/l range. Both active and total ghrelin can be measured. Circulating ghrelin concentrations rise before eating and fall afterward, more strongly in response to protein and carbohydrate than to lipids. # Ghrelin receptor The ghrelin receptor GHS-R1a (a splice-variant of the growth hormone secretagogue receptor, with the GHS-R1b splice being inactive) is involved in mediating a wide variety of biological effects of ghrelin, including: stimulation of growth hormone release, increase in hunger, modulation of glucose and lipid metabolism, regulation of gastrointestinal motility and secretion, protection of neuronal and cardiovascular cells, and regulation of immune function. They are present in high density in the hypothalamus and pituitary, on the vagus nerve (on both afferent cell bodies and afferent nerve endings) and throughout the gastrointestinal tract. # Locations of action ## Gastrointestinal tract Ghrelin promotes intestinal cell proliferation and inhibits apoptosis during inflammatory states and oxidative stress. It also suppresses pro-inflammatory mechanisms and augments anti-inflammatory mechanisms, thus creating a possibility of its therapeutic use in various gastrointestinal inflammatory conditions, including colitis, ischemia reperfusion injury, and sepsis. Animal models of colitis, ischemia reperfusion, and sepsis-related gut dysfunction have been shown to benefit from therapeutic doses of ghrelin. It has also been shown to have regenerative capacity and is beneficial in mucosal injury to the stomach. Ghrelin promotes gastrointestinal and pancreatic malignancy. ## Pancreas Ghrelin inhibits glucose-stimulated insulin secretion from beta cells in the pancreatic islets. Ghrelin does this indirectly by promoting local negative feedback mediated by somatostatin from pancreatic delta cells, which selectively express the ghrelin receptor. ## Glucose metabolism The entire ghrelin system (dAG, AG, GHS-R and GOAT) has a gluco-regulatory action. ## Nervous system ### Learning and memory The hippocampus plays a significant role in neurotrophy: the cognitive adaptation to changing environments and the process of learning and it is a potent stimulator of growth hormone. Animal models indicate that ghrelin may enter the hippocampus from the bloodstream, altering nerve-cell connections, and so altering learning and memory. It is suggested that learning may be best during the day and when the stomach is empty, since ghrelin levels are higher at these times. A similar effect on human memory performance is possible. In rodents, X/A-like cells produce ghrelin. ### Depression Ghrelin knock-out mice (who never express ghrelin) have increased anxiety in response to a variety of stressors, such as acute restraint stress and social stress in experimental settings. In normal mice, ghrelin can stimulate the hypothalamic-pituitary-adrenal axis, from the anterior pituitary. Ghrelin has been shown to have implications for depression prevention. Antidepressant-like attributes were demonstrated when mice with high levels of ghrelin and mice with the ghrelin gene knocked out underwent social defeat stress and then were placed in the forced swim tank. Mice with elevated ghrelin swam more than ghrelin deficient mice. These ghrelin-deficient mice exhibited more social avoidance as well. These mice did not exhibit depression-like behaviors when injected with a commonly prescribed antidepressant, suggesting that ghrelin acts as a short-term natural adaptation against depression. ### Sleep duration Short sleep duration is associated with high levels of ghrelin and obesity. An inverse relationship between the hours of sleep and blood plasma concentrations of ghrelin exists; as the hours of sleep increase, ghrelin levels trend lower and obesity is less likely. ### Stress-induced fear Prior stress exposure heightens fear learning during Pavlovian fear conditioning. Stress-related increases in ghrelin circulation were shown to be necessary and sufficient for stress to increase fear learning. Ghrelin was found to be upregulated by stress even in the absence of adrenal hormones. Blocking the ghrelin receptor during stress abolished stress-related enhancement of fear memory without blunting other markers of stress. These results suggest that ghrelin is a novel branch of the stress response. Human studies are needed to translate the use of anti-ghrelin treatments to prevent stress-induced psychiatric disorders. ### Substantia nigra function Ghrelin, through its receptor increases the concentration of dopamine in the substantia nigra. ## Reproductive system Ghrelin has inhibitory effects on gonadotropin-releasing hormone (GnRH) secretion. It may cause decreased fertility. ## Fetus and neonate - Ghrelin is produced early by the fetal lung and promotes lung growth. - Cord blood levels of active and total ghrelin show a correlation between ghrelin levels and birth weight. # Anorexia and obesity - Ghrelin levels in the plasma of obese individuals are lower than those in leaner individuals, suggesting that ghrelin does not contribute to obesity, except in the cases of Prader-Willi syndrome-induced obesity, where high ghrelin levels are correlated with increased food intake. However, it is also found that consumption of food for pleasure increased peripheral levels of both ghrelin and the endocannabinoid 2-arachidonoyl-glycerol (2-AG) in healthy humans, and this hedonic eating influences food intake and, ultimately, body mass. - Those with anorexia nervosa have high plasma levels of ghrelin compared to both the constitutionally thin and normal-weight controls. - The level of ghrelin increases during the time of day from midnight to dawn in thinner people, which suggests there is a flaw in the circadian rhythm of obese individuals. - Ghrelin levels reflect release in a circadian rhythm, which can be interrupted by exposure to light at night. - Short sleep duration may also lead to obesity, through an increase of appetite via hormonal changes. - Lack of sleep increases ghrelin and decreases leptin, both of which result in increased hunger and obesity. - Ghrelin levels are high in patients with cancer-induced cachexia. # Disease management ## Gastric bypass surgery Gastric bypass surgery not only reduces the gut's capacity for food but also dramatically lowers ghrelin levels compared to both lean controls and those that lost weight through dieting alone. However, studies are conflicting as to whether or not ghrelin levels return to nearly normal with gastric bypass patients in the long term after weight loss has stabilized. Bariatric surgeries involving vertical-sleeve gastrectomy reduce plasma ghrelin levels by about 60% in the long term. # Aging Ghrelin plasma concentration increases with age and this may contribute to the tendency for weight gain as people age. # Future clinical uses - Synthetic ghrelin administration for cachexia of any cause and for hemodialysis patients is being investigated. - Ghrelin suppresses seizures in animal models and is being investigated. - Ghrelin is a gastric pro-kinetic and may be useful in the treatment of gastroparesis.	Ghrelin Ghrelin (pronounced /ˈɡrɛlɪn/), the "hunger hormone", also known as lenomorelin (INN), is a peptide hormone produced by ghrelinergic cells in the gastrointestinal tract[1][2] that functions as a neuropeptide in the central nervous system.[3] Besides regulating appetite, ghrelin also plays a significant role in regulating the distribution and rate of use of energy.[4] When the stomach is empty, ghrelin is secreted. When the stomach is stretched, secretion stops.a It acts on hypothalamic brain cells both to increase hunger, and to increase gastric acid secretion and gastrointestinal motility to prepare the body for food intake.[5] The receptor for ghrelin, the ghrelin/growth hormone secretagogue receptor (GHS-R), is found on the same cells in the brain as the receptor for leptin, the satiety hormone that has opposite effects from ghrelin.[6] Ghrelin also plays an important role in regulating reward perception in dopamine neurons that link the ventral tegmental area to the nucleus accumbens[7][8] (a site that plays a role in processing sexual desire, reward, and reinforcement, and in developing addictions) through its colocalized receptors and interaction with dopamine and acetylcholine.[3][9] Ghrelin is encoded by the GHRL gene and is presumably produced from the cleavage of the prepropeptide ghrelin/obestatin. Full-length preproghrelin is homologous to promotilin and both are members of the motilin family. Unlike the case of many other endogenous peptides, ghrelin is able to cross the blood-brain-barrier, giving exogenously-administered ghrelin unique clinical potential.[10] # History and name Ghrelin was discovered after the ghrelin receptor (called growth hormone secretagogue type 1A receptor or GHS-R) was discovered in 1996[11] and was reported in 1999.[12] The hormone name is based on its role as a growth hormone-releasing peptide, with reference to the Proto-Indo-European root gʰre-, meaning "to grow".[13] # Gene, transcription products, and structure The GHRL gene produces mRNA which has four exons. Five products arise: the first is the 117-amino acid preproghrelin. (It is homologous to promotilin; both are members of the motilin family). It is cleaved to produce proghrelin which is cleaved to produce a 28-amino acid ghrelin (unacylated) and C-ghrelin(acylated). Obestatin is presumed to be cleaved from C-ghrelin.[14] Ghrelin only becomes active when caprylic (octanoic) acid is linked posttranslationally to serine at the 3-position by the enzyme ghrelin O-acyltransferase (GOAT). It is located on the cell membrane of ghrelin cells in the stomach and pancreas.[15] The non-octanoylated form is desacyl ghrelin. It does not activate the GHS-R receptor but does have other effects: cardiac,[16] anti-ghrelin,[17] appetite stimulation,[18] and inhibition of hepatic glucose output[19] Side-chains other than octanoyl have also been observed: these can also trigger the ghrelin receptor.[20] In particular, decanoyl ghrelin has been found to constitute a significant portion of circulating ghrelin in mice, but as of 2011 its presence in humans has not been established.[21] # Ghrelin cells ## Alternative names The ghrelin cell is also known as an A-like cell (pancreas), X-cell (for unknown function), X/A-like cell (rats), Epsilon cell (pancreas), P/D sub 1 cell (humans) and Gr cell (abbreviation for ghrelin cell).[22] ## Location Ghrelin cells are found mainly in the stomach[23] and duodenum, but also in the jejunum, lungs, pancreatic islets,[24] gonads, adrenal cortex, placenta, and kidney. It has recently been shown that ghrelin is produced locally in the brain[25] ## Features Ghrelin cells are found in oxyntic glands (20% of cells),[26] pyloric glands, and small intestine. They are ovoid cells with granules.[27] They have gastrin receptors.[28] Some produce nesfatin-1.[29] Ghrelin cells are not terminally differentiated in the pancreas: they are progenitor cells that can give rise to A-cells, PP cells and Beta-cells there.[30] # Function and mechanism of action Ghrelin is a participant in regulating the complex process of energy homeostasis which adjusts both energy input – by adjusting hunger signals – and energy output – by adjusting the proportion of energy going to ATP production, fat storage, glycogen storage, and short-term heat loss. The net result of these processes is reflected in body weight, and is under continuous monitoring and adjustment based on metabolic signals and needs. At any given moment in time, it may be in equilibrium or disequilibrium. Gastric-brain communication is an essential part of energy homeostasis, and several communication pathways are probable, including the gastric intracellular mTOR/S6K1 pathway mediating the interaction among ghrelin, nesfatin and endocannabinoid gastric systems,[31] and both afferent and efferent vagal signals. Ghrelin and synthetic ghrelin mimetics (growth hormone secretagogues) increase body weight and fat mass[32][33][34] by triggering receptors in the arcuate nucleus[35][36] that include the orexigenic neuropeptide Y (NPY) and agouti-related protein (AgRP) neurons.[37][38] Ghrelin-responsiveness of these neurons is both leptin- and insulin-sensitive.[39] Ghrelin reduces the mechanosensitivity of gastric vagal afferents, so they are less sensitive to gastric distension.[40] In addition to its function in energy homeostasis, ghrelin also activates the cholinergic–dopaminergic reward link in inputs to the ventral tegmental area and in the mesolimbic pathway,[7] a circuit that communicates the hedonic and reinforcing aspects of natural rewards,[3] such as food and addictive drugs such as ethanol.[39][41][42] Ghrelin receptors are located on neurons in this circuit.[3][8] Hypothalamic ghrelin signalling is required for reward from alcohol[43] and palatable/rewarding foods.[44][45] Ghrelin has been linked to inducing appetite and feeding behaviors. Circulating ghrelin levels are the highest right before a meal and the lowest right after.[46][47] Injections of ghrelin in both humans and rats have been shown to increase food intake in a dose-dependent manner.[48] So the more ghrelin that is injected the more food that is consumed. However, ghrelin does not increase meal size, only meal number.[49] Ghrelin injections also increase an animal's motivation to seek out food, behaviors including increased sniffing, foraging for food, and hoarding food. Body weight is regulated through energy balance, the amount of energy taken in versus the amount of energy expended over an extended period of time. Studies have shown that ghrelin levels are negatively correlated with weight. This data suggests that ghrelin functions as an adiposity signal, a messenger between the body's energy stores and the brain.[5] # Blood levels Blood levels are in the pmol/l range. Both active and total ghrelin can be measured.[50] Circulating ghrelin concentrations rise before eating and fall afterward,[46] more strongly in response to protein and carbohydrate than to lipids.[21] # Ghrelin receptor The ghrelin receptor GHS-R1a (a splice-variant of the growth hormone secretagogue receptor, with the GHS-R1b splice being inactive) is involved in mediating a wide variety of biological effects of ghrelin, including: stimulation of growth hormone release, increase in hunger, modulation of glucose and lipid metabolism, regulation of gastrointestinal motility and secretion, protection of neuronal and cardiovascular cells, and regulation of immune function.[51] They are present in high density in the hypothalamus and pituitary, on the vagus nerve (on both afferent cell bodies and afferent nerve endings) and throughout the gastrointestinal tract.[15][40] # Locations of action ## Gastrointestinal tract Ghrelin promotes intestinal cell proliferation and inhibits apoptosis during inflammatory states and oxidative stress.[52][53] It also suppresses pro-inflammatory mechanisms and augments anti-inflammatory mechanisms, thus creating a possibility of its therapeutic use in various gastrointestinal inflammatory conditions, including colitis, ischemia reperfusion injury, and sepsis.[54][55] Animal models of colitis, ischemia reperfusion, and sepsis-related gut dysfunction have been shown to benefit from therapeutic doses of ghrelin.[54][55] It has also been shown to have regenerative capacity and is beneficial in mucosal injury to the stomach.[56] Ghrelin promotes gastrointestinal and pancreatic malignancy.[57][58][59] ## Pancreas Ghrelin inhibits glucose-stimulated insulin secretion from beta cells in the pancreatic islets. Ghrelin does this indirectly by promoting local negative feedback mediated by somatostatin from pancreatic delta cells, which selectively express the ghrelin receptor.[60] ## Glucose metabolism The entire ghrelin system (dAG, AG, GHS-R and GOAT) has a gluco-regulatory action.[61] ## Nervous system ### Learning and memory The hippocampus plays a significant role in neurotrophy: the cognitive adaptation to changing environments and the process of learning[62][63] and it is a potent stimulator of growth hormone.[12] Animal models indicate that ghrelin may enter the hippocampus from the bloodstream, altering nerve-cell connections, and so altering learning and memory.[64] It is suggested that learning may be best during the day and when the stomach is empty, since ghrelin levels are higher at these times. A similar effect on human memory performance is possible.[62] In rodents, X/A-like cells produce ghrelin.[65] ### Depression Ghrelin knock-out mice (who never express ghrelin) have increased anxiety in response to a variety of stressors, such as acute restraint stress and social stress in experimental settings.[66] In normal mice, ghrelin can stimulate the hypothalamic-pituitary-adrenal axis, from the anterior pituitary.[66] Ghrelin has been shown to have implications for depression prevention. Antidepressant-like attributes were demonstrated when mice with high levels of ghrelin and mice with the ghrelin gene knocked out underwent social defeat stress and then were placed in the forced swim tank. Mice with elevated ghrelin swam more than ghrelin deficient mice.[67] These ghrelin-deficient mice exhibited more social avoidance as well. These mice did not exhibit depression-like behaviors when injected with a commonly prescribed antidepressant, suggesting that ghrelin acts as a short-term natural adaptation against depression. ### Sleep duration Short sleep duration is associated with high levels of ghrelin and obesity. An inverse relationship between the hours of sleep and blood plasma concentrations of ghrelin exists; as the hours of sleep increase, ghrelin levels trend lower and obesity is less likely.[68] ### Stress-induced fear Prior stress exposure heightens fear learning during Pavlovian fear conditioning. Stress-related increases in ghrelin circulation were shown to be necessary and sufficient for stress to increase fear learning. Ghrelin was found to be upregulated by stress even in the absence of adrenal hormones. Blocking the ghrelin receptor during stress abolished stress-related enhancement of fear memory without blunting other markers of stress. These results suggest that ghrelin is a novel branch of the stress response.[69] Human studies are needed to translate the use of anti-ghrelin treatments to prevent stress-induced psychiatric disorders. ### Substantia nigra function Ghrelin, through its receptor increases the concentration of dopamine in the substantia nigra.[70] ## Reproductive system Ghrelin has inhibitory effects on gonadotropin-releasing hormone (GnRH) secretion. It may cause decreased fertility.[71] ## Fetus and neonate - Ghrelin is produced early by the fetal lung and promotes lung growth.[72] - Cord blood levels of active and total ghrelin show a correlation between ghrelin levels and birth weight.[50] # Anorexia and obesity - Ghrelin levels in the plasma of obese individuals are lower than those in leaner individuals,[73] suggesting that ghrelin does not contribute to obesity, except in the cases of Prader-Willi syndrome-induced obesity, where high ghrelin levels are correlated with increased food intake.[74][75] However, it is also found that consumption of food for pleasure increased peripheral levels of both ghrelin and the endocannabinoid 2-arachidonoyl-glycerol (2-AG) in healthy humans, and this hedonic eating influences food intake and, ultimately, body mass.[76] - Those with anorexia nervosa have high plasma levels of ghrelin[77] compared to both the constitutionally thin and normal-weight controls.[78][79] - The level of ghrelin increases during the time of day from midnight to dawn in thinner people, which suggests there is a flaw in the circadian rhythm of obese individuals.[80] - Ghrelin levels reflect release in a circadian rhythm, which can be interrupted by exposure to light at night.[81] - Short sleep duration may also lead to obesity, through an increase of appetite via hormonal changes.[82] - Lack of sleep increases ghrelin and decreases leptin, both of which result in increased hunger and obesity. - Ghrelin levels are high in patients with cancer-induced cachexia.[83] # Disease management ## Gastric bypass surgery Gastric bypass surgery not only reduces the gut's capacity for food but also dramatically lowers ghrelin levels compared to both lean controls and those that lost weight through dieting alone.[84] However, studies are conflicting as to whether or not ghrelin levels return to nearly normal with gastric bypass patients in the long term after weight loss has stabilized.[85] Bariatric surgeries involving vertical-sleeve gastrectomy reduce plasma ghrelin levels by about 60% in the long term.[86] # Aging Ghrelin plasma concentration increases with age and this may contribute to the tendency for weight gain as people age.[87][88] # Future clinical uses - Synthetic ghrelin administration for cachexia of any cause[89] and for hemodialysis patients[90] is being investigated. - Ghrelin suppresses seizures in animal models and is being investigated.[91] - Ghrelin is a gastric pro-kinetic and may be useful in the treatment of gastroparesis.[92]	https://www.wikidoc.org/index.php/Ghrelin
406c9e33618c7aebbd2b55213b399e0d7358b542	wikidoc	Gingiva	Gingiva # Overview The gingiva (sing. and plur.: gingiva), or gums, consists of the mucosal tissue that lies over the alveolar bone. # General Description Gingiva are part of the soft tissue lining of the mouth. They surround the teeth and provide a seal around them. Compared with the soft tissue linings of the lips and cheeks, most of the gingiva are tightly bound to the underlying bone and are designed to resist the friction of food passing over them. Healthy gingiva is usually coral pink, but may contain physiologic pigmentation. Changes in color, particularly increased redness, together with edema and an increased tendency to bleed, suggest an inflammation that is possibly due to the accumulation of bacterial plaque. # Subdivisions of Gingiva The gingiva is divided anatomically into marginal, attached and interdental areas. ## Marginal Gingiva The marginal gingiva is the terminal edge of gingiva surrounding the teeth in collar like fashion. In about 50% of individuals, it is demarcated from the adjacent, attached gingiva by a shallow linear depression, the free gingival groove. Usually about 1 mm wide, it forms the soft tissue wall of the gingival sulcus. The marginal gingiva is supported and stabilized by the gingival fibers. ## Attached Gingiva The attached gingiva is continuous with the marginal gingiva. It is firm, resilient, and tightly bound to the underlying periosteum of alveolar bone. The facial aspect of the attached gingiva extends to the relatively loose and movable alveolar mucosa, from which it is demarcated by the mucogingival junction. Attached gingiva may present with surface stippling. ## Interdental Gingiva The interdental gingiva occupies the gingival embrasure, which is the interproximal space beneath the area of tooth contact. The interdental gingiva can be pyramidal or have a "col" shape. # Diseases of the Gingiva The gingival cavity microecosystem, fueled by food residues and saliva, can support the growth of many microorganisms, of which some can be injurious to health. Improper or insufficient oral hygiene can thus lead to many gingival and periodontal disorders, including gingivitis or pyorrhea, which are major causes for tooth failure. Recent studies have also shown that Anabolic steroids are also closely associated with gingival enlargement requiring a gingivectomy for many cases. # Characteristics of Healthy Gingiva ## Colour Healthy gingiva usually has a colour that has been described as "coral pink." Other colours like red, white, and blue can signify inflammation (gingivitis) or pathology. Although the text book color of gingiva is "coral pink", normal racial pigmentation makes the gingiva appear darker. Because the color of gingiva varies due to racial pigmentation, uniformity of colour is more important than the underlying color itself. ## Contour Healthy gingiva has a smooth arcuate or scalloped appearance around each tooth. Healthy gingiva fills and fits each interdental space, unlike the swollen gingiva papilla seen in gingivitis or the empty interdental embrasure seen in periodontal disease. Healthy gums hold tight to each tooth in that the gingival surface narrows to a "knife-edge" thins at the free gingival margin. On the other hand, inflamed gums have a "puffy" or "rolled" margin. ## Texture Healthy gingiva has a firm texture that is resistant to movement, and the surface texture often exhibits surface stippling. Unhealthy gingiva, on the other hand, is often swollen and mushy. ## Reaction to Disturbance Healthy gums usually have no reaction to normal disturbance such as brushing or periodontal probing. Unhealthy gums on the other hand will show bleeding on probing (BOP) and/or purulent exudate (pus). # Additional images - Mouth (oral cavity) - Mouth	Gingiva Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] # Overview Template:Infobox Anatomy The gingiva (sing. and plur.: gingiva), or gums, consists of the mucosal tissue that lies over the alveolar bone. # General Description Gingiva are part of the soft tissue lining of the mouth. They surround the teeth and provide a seal around them. Compared with the soft tissue linings of the lips and cheeks, most of the gingiva are tightly bound to the underlying bone and are designed to resist the friction of food passing over them. Healthy gingiva is usually coral pink, but may contain physiologic pigmentation. Changes in color, particularly increased redness, together with edema and an increased tendency to bleed, suggest an inflammation that is possibly due to the accumulation of bacterial plaque. # Subdivisions of Gingiva The gingiva is divided anatomically into marginal, attached and interdental areas. ## Marginal Gingiva The marginal gingiva is the terminal edge of gingiva surrounding the teeth in collar like fashion. In about 50% of individuals, it is demarcated from the adjacent, attached gingiva by a shallow linear depression, the free gingival groove. Usually about 1 mm wide, it forms the soft tissue wall of the gingival sulcus. The marginal gingiva is supported and stabilized by the gingival fibers. ## Attached Gingiva The attached gingiva is continuous with the marginal gingiva. It is firm, resilient, and tightly bound to the underlying periosteum of alveolar bone. The facial aspect of the attached gingiva extends to the relatively loose and movable alveolar mucosa, from which it is demarcated by the mucogingival junction. Attached gingiva may present with surface stippling. ## Interdental Gingiva The interdental gingiva occupies the gingival embrasure, which is the interproximal space beneath the area of tooth contact. The interdental gingiva can be pyramidal or have a "col" shape. # Diseases of the Gingiva The gingival cavity microecosystem, fueled by food residues and saliva, can support the growth of many microorganisms, of which some can be injurious to health. Improper or insufficient oral hygiene can thus lead to many gingival and periodontal disorders, including gingivitis or pyorrhea, which are major causes for tooth failure. Recent studies have also shown that Anabolic steroids are also closely associated with gingival enlargement requiring a gingivectomy for many cases.[2] # Characteristics of Healthy Gingiva ## Colour Healthy gingiva usually has a colour that has been described as "coral pink." Other colours like red, white, and blue can signify inflammation (gingivitis) or pathology. Although the text book color of gingiva is "coral pink", normal racial pigmentation makes the gingiva appear darker. Because the color of gingiva varies due to racial pigmentation, uniformity of colour is more important than the underlying color itself. ## Contour Healthy gingiva has a smooth arcuate or scalloped appearance around each tooth. Healthy gingiva fills and fits each interdental space, unlike the swollen gingiva papilla seen in gingivitis or the empty interdental embrasure seen in periodontal disease. Healthy gums hold tight to each tooth in that the gingival surface narrows to a "knife-edge" thins at the free gingival margin. On the other hand, inflamed gums have a "puffy" or "rolled" margin. ## Texture Healthy gingiva has a firm texture that is resistant to movement, and the surface texture often exhibits surface stippling. Unhealthy gingiva, on the other hand, is often swollen and mushy. ## Reaction to Disturbance Healthy gums usually have no reaction to normal disturbance such as brushing or periodontal probing. Unhealthy gums on the other hand will show bleeding on probing (BOP) and/or purulent exudate (pus). # Additional images - Mouth (oral cavity) - Mouth	https://www.wikidoc.org/index.php/Gingiva
1de1780c4ef676fd465877e48ca113580fe4dd1e	wikidoc	Ginseng	Ginseng Ginseng refers to species within Panax, a genus of 11 species of slow-growing perennial plants with fleshy roots, in the family Araliaceae. They grow in the Northern Hemisphere in eastern Asia (mostly northern China, Korea, and eastern Siberia), typically in cooler climates; Panax vietnamensis, discovered in Vietnam, is the southernmost ginseng found. This article focuses on the Series Panax ginsengs, which are the adaptogenic herbs, principally Panax ginseng and Panax quinquefolius. Ginseng is characterized by the presence of ginsenosides. Siberian ginseng (Eleutherococcus senticosus) is not a ginseng at all. It is another adaptogen, but a different species named "Siberian ginseng" as a marketing ploy; instead of a fleshy root, it has a woody root; instead of ginsenosides, eleutherosides are present, (see below). # Etymology The English word ginseng derives from the Chinese term rénshēn (simplified: 人参; traditional: 人蔘), literally "man root" (referring to the root's characteristic forked shape, resembling the legs of a man). The difference between rénshēn and "ginseng" is explained by the fact that the English pronunciation derives from a Japanese reading of these Chinese characters. However, the current Japanese word for these characters 人参 (ninjin) means carrot, and ginseng is referred to in Japanese as 朝鮮人参 (chosen ninjin). The Korean name is 고려인삼 高麗人参 (goryo insam). The botanical name Panax means "all-heal" in Greek, and was applied to this genus because Linnaeus was aware of its wide use in Chinese medicine. # Traditional uses Both American and Panax (Asian) ginseng rhizomes are taken orally as adaptogens, aphrodisiacs, nourishing stimulants, and in the treatment of type II diabetes, including sexual dysfunction in men. The rhizome is most often available in dried form, either in whole or sliced form. Ginseng leaf, although not as highly prized, is sometimes also used; as with the rhizome it is most often available in dried form. This ingredient may also be found in some popular Energy Drinks: usually the "tea" varieties or Functional Foods. Usually ginseng is in subclinical doses and it does not have measurable medicinal effects. It can be found in cosmetic preparations as well, with similar lack of effect. It is considered a wasteful use of important herbs by herbalists. Ginseng root can be double steamed with chicken meat as a soup. (See samgyetang.) # Modern science and ginseng As with herbalism in general, ginseng's medical efficacy remains controversial. It has been difficult to verify the medicinal benefits of ginseng using modern science, as there are contradictory results from different studies, possibly due to the wide variety and quality of ginseng used in studies. Another issue is the profit potential of corporate research since ginseng cannot be patented.OR As a result, high-quality studies of the effects of ginseng are rare. Incidentally, one of the better studies involving ginseng actually uses a proprietary ginseng extract. Ginseng is promoted as an adaptogen (a product that increases the body's resistance to stress), one which can to a certain extent be supported with reference to its anticarcinogenic and antioxidant properties, although animal experiments to determine whether longevity and health were increased in the presence of stress gave negative results. A comparative, randomized and double-blind study at the National Autonomous University of Mexico does indicate it to be "a promising dietary supplement" when assessed for an increase in quality of life . Panax ginseng appear to inhibit some characteristics associated with cancer in animal models; nevertheless, this effect is unclear in humans. There are references in the literature, including seemingly authoritative compendiums that appear to show interactions with ginseng. Herbalist Jonathan Treasure of the United States National Institute of Mental Health traces the growth of misinformation on an alleged adverse herb-drug interaction between the monoamine oxidase inhibitor phenelzine and Asian ginseng (Panax ginseng C.A. Meyer). This originally was mentioned in a 1985 editorial by Shader and Greenblatt in the Journal of Clinical Psychopharmacology. Shader and Greenblatt devoted a couple of lines to the case of 64 year-old woman who took an undisclosed dose for an undisclosed time of a dietary supplement product called “Natrol High” while concurrently taking phenelzine 60 mg qd. She experienced symptoms of “insomnia, headache, and tremulousness”. Treasure contacted Natrol by email and discovered within ten minutes that there was no Panax ginseng in the formula, but instead eleutherococcus which was then called by the popular name "Siberian ginseng" and it was given in a subclinical dosage mixed with a variety of other herbs. The purported interaction effects are well-known side effects of phenelzine alone, which had been given in a high dosage and are not at all suggestive of eleutherococcus. However this misinformed article with a misidentified herb has been picked up in literature searches, megastudies and is now documented by conventional medical authorities such as Stockley’s , and is repeated in several botanical monographs e.g. World Health Organization (WHO # Ginseng and Reproductive Activity A 2002 study by the Southern Illinois University School of Medicine (published in the annals of the New York Academy of Sciences) found that in laboratory animals, both Asian and American forms of ginseng enhance libido and copulatory performance. These effects of ginseng may not be due to changes in hormone secretion, but to direct effects of ginseng, or its ginsenoside components, on the central nervous system and gonadal tissuesIn males, ginsenosides can facilitate penile erection. This is consistent with traditional Chinese medicine and Native American medicinal uses of ginseng. # Side effects One of Panax ginseng's most common side-effects is the inability to sleep. Other side-effects include nausea, diarrhea, euphoria, headaches, epistaxis, high blood pressure, low blood pressure, mastalgia, and vaginal bleeding. # Overdose The common adaptogen ginsengs (Panax ginseng and Panax quinquefolia) are generally considered to be relatively safe even in large amounts. Panax ginseng is not recommended within Chinese Medicine to be administered along with anti-infective herbs unless a person is quite debilitated, because of the fear that the pathogen will be tonified. Herbalists in China believed this and according to Xu Dachun in his brief essay on ginseng (1757 A.D., during the Qing Dynasty): "if one administers Ginseng of a purely supplementing nature, then one will merely supplement the evil influences and help them settle down. In minor cases, the evil influences will, as a result of such mistaken therapy, never leave the body again. In serious cases, death is inevitable." # Common classification # Panax quinquefolius American ginseng (root) # Panax ginseng Asian ginseng (root) ## Red ginseng Red ginseng (Korean=홍삼, Template:Zh-st), is Panax ginseng that has been heated, either through steaming or sun-drying. It is frequently marinated in an herbal brew which results in the root becoming extremely brittle. This version of ginseng is traditionally associated with stimulating sexual function and increasing energy. Red ginseng is always produced from cultivated roots, usually from either China or South Korea. In 2002, a preliminary double-blind, crossover study of Korean red ginseng's effects on impotence reported that it can be an effective alternative for treating male erectile dysfunction. A study shows that Red ginseng reduces the relapse of gastric cancer versus control A study of ginseng's effects on rats show that while both White ginseng and Red ginseng reduce the incidence of cancer, the effects appear to be greater with Red ginseng. Falcarinol, a seventeen-carbon diyne fatty alcohol was isolated from carrot and red ginseng, shown to have potent anticancer properties on primary mammary epithelial (breast cancer) cells. Other acetylenic fatty alcohols in ginseng (panaxacol, panaxydol, panaxytriol) have antibiotic properties. ## Wild ginseng Wild ginseng is ginseng that has not been planted and cultivated domestically, rather it is that which grows naturally and is harvested from wherever it is found to be growing. It is considered to be superior to field farmed ginseng by various authorities, and it has been shown to contain higher levels of ginsenoside. Wild ginseng is relatively rare and even increasingly endangered, due in large part to high demand for the product in recent years, which has led to the wild plants being sought out and harvested faster than new ones can grow (it requires years for a ginseng root to reach maturity). Wild ginseng can be either Asian or American and can be processed to be red ginseng. There are woods grown American ginseng programs in Maine, Tennessee, Virginia and North Carolina. and United Plant Savers has been encouraging the woods planting of ginseng both to restore natural habitats and to remove pressure from any remaining wild ginseng, and they offer both advice and sources of rootlets. Woods grown plants have comparable value to wild grown ginseng of similar age. ## Ginseng alternatives These mostly adaptogenic plants are sometimes referred to as ginsengs, but they are either from a different family or genus. Only Jiaogulan actually contains ginsenosides, although ginsenosides alone do not determine the effectiveness of ginseng. Since each of these plants have different uses, one should research their properties before using. Descriptions and differentiation can be found in David Winston and Steven Maimes book Adaptogens - Gynostemma pentaphyllum (Southern ginseng, aka Jiaogulan) - Eleutherococcus senticosus (Siberian ginseng) - Pseudostellaria heterophylla (Prince ginseng) - Withania somnifera (Indian ginseng, aka Ashwagandha) - Pfaffia paniculata (Brazilian ginseng) - Lepidium meyenii (Peruvian ginseng, aka Maca) Other plants which are referred to as ginsengs may not be adaptogens (although notoginseng is in the Panax family): - Angelica sinensis (Female ginseng, aka Dong Quai) - Panax notoginseng (San qi, hemostatic ingredient in Yunnan Bai Yao)	Ginseng Ginseng refers to species within Panax, a genus of 11 species of slow-growing perennial plants with fleshy roots, in the family Araliaceae. They grow in the Northern Hemisphere in eastern Asia (mostly northern China, Korea, and eastern Siberia), typically in cooler climates; Panax vietnamensis, discovered in Vietnam, is the southernmost ginseng found. This article focuses on the Series Panax ginsengs, which are the adaptogenic herbs, principally Panax ginseng and Panax quinquefolius. Ginseng is characterized by the presence of ginsenosides. Siberian ginseng (Eleutherococcus senticosus) is not a ginseng at all. It is another adaptogen, but a different species named "Siberian ginseng" as a marketing ploy; instead of a fleshy root, it has a woody root; instead of ginsenosides, eleutherosides are present, (see below). # Etymology The English word ginseng derives from the Chinese term rénshēn (simplified: 人参; traditional: 人蔘), literally "man root" (referring to the root's characteristic forked shape, resembling the legs of a man). The difference between rénshēn and "ginseng" is explained by the fact that the English pronunciation derives from a Japanese reading of these Chinese characters. However, the current Japanese word for these characters 人参 (ninjin) means carrot, and ginseng is referred to in Japanese as 朝鮮人参 (chosen ninjin). The Korean name is 고려인삼 高麗人参 (goryo insam). The botanical name Panax means "all-heal" in Greek, and was applied to this genus because Linnaeus was aware of its wide use in Chinese medicine. # Traditional uses Both American and Panax (Asian) ginseng rhizomes are taken orally as adaptogens, aphrodisiacs, nourishing stimulants, and in the treatment of type II diabetes, including sexual dysfunction in men. The rhizome is most often available in dried form, either in whole or sliced form. Ginseng leaf, although not as highly prized, is sometimes also used; as with the rhizome it is most often available in dried form. This ingredient may also be found in some popular Energy Drinks: usually the "tea" varieties or Functional Foods. Usually ginseng is in subclinical doses and it does not have measurable medicinal effects. It can be found in cosmetic preparations as well, with similar lack of effect. It is considered a wasteful use of important herbs by herbalists. Ginseng root can be double steamed with chicken meat as a soup. (See samgyetang.) # Modern science and ginseng As with herbalism in general, ginseng's medical efficacy remains controversial. It has been difficult to verify the medicinal benefits of ginseng using modern science, as there are contradictory results from different studies, possibly due to the wide variety and quality of ginseng used in studies. Another issue is the profit potential of corporate research since ginseng cannot be patented.OR As a result, high-quality studies of the effects of ginseng are rare. Incidentally, one of the better studies involving ginseng actually uses a proprietary ginseng extract. [1] Ginseng is promoted as an adaptogen (a product that increases the body's resistance to stress), one which can to a certain extent be supported with reference to its anticarcinogenic and antioxidant properties,[2] although animal experiments to determine whether longevity and health were increased in the presence of stress gave negative results.[3] A comparative, randomized and double-blind study at the National Autonomous University of Mexico does indicate it to be "a promising dietary supplement" when assessed for an increase in quality of life [4]. Panax ginseng appear to inhibit some characteristics associated with cancer in animal models; nevertheless, this effect is unclear in humans.[5] There are references in the literature, including seemingly authoritative compendiums that appear to show interactions with ginseng. Herbalist Jonathan Treasure of the United States National Institute of Mental Health traces the growth of misinformation on an alleged adverse herb-drug interaction between the monoamine oxidase inhibitor phenelzine and Asian ginseng (Panax ginseng C.A. Meyer). This originally was mentioned in a 1985 editorial by Shader and Greenblatt in the Journal of Clinical Psychopharmacology. Shader and Greenblatt devoted a couple of lines to the case of 64 year-old woman who took an undisclosed dose for an undisclosed time of a dietary supplement product called “Natrol High” while concurrently taking phenelzine 60 mg qd. She experienced symptoms of “insomnia, headache, and tremulousness”. Treasure contacted Natrol by email and discovered within ten minutes that there was no Panax ginseng in the formula, but instead eleutherococcus which was then called by the popular name "Siberian ginseng" and it was given in a subclinical dosage mixed with a variety of other herbs. The purported interaction effects are well-known side effects of phenelzine alone, which had been given in a high dosage and are not at all suggestive of eleutherococcus. However this misinformed article with a misidentified herb has been picked up in literature searches, megastudies and is now documented by conventional medical authorities such as Stockley’s , and is repeated in several botanical monographs e.g. World Health Organization (WHO 1999).[6][7][8] # Ginseng and Reproductive Activity A 2002 study by the Southern Illinois University School of Medicine (published in the annals of the New York Academy of Sciences) found that in laboratory animals, both Asian and American forms of ginseng enhance libido and copulatory performance. These effects of ginseng may not be due to changes in hormone secretion, but to direct effects of ginseng, or its ginsenoside components, on the central nervous system and gonadal tissues[9]In males, ginsenosides can facilitate penile erection.[10] This is consistent with traditional Chinese medicine and Native American medicinal uses of ginseng. # Side effects One of Panax ginseng's most common side-effects is the inability to sleep.[11] Other side-effects include nausea, diarrhea, euphoria, headaches, epistaxis, high blood pressure, low blood pressure, mastalgia, and vaginal bleeding.[12] # Overdose The common adaptogen ginsengs (Panax ginseng and Panax quinquefolia) are generally considered to be relatively safe even in large amounts. Panax ginseng is not recommended within Chinese Medicine to be administered along with anti-infective herbs unless a person is quite debilitated, because of the fear that the pathogen will be tonified. Herbalists in China believed this and according to Xu Dachun in his brief essay on ginseng (1757 A.D., during the Qing Dynasty): "if one administers Ginseng of a purely supplementing nature, then one will merely supplement the evil influences and help them settle down. In minor cases, the evil influences will, as a result of such mistaken therapy, never leave the body again. In serious cases, death is inevitable."[13] # Common classification # Panax quinquefolius American ginseng (root) # Panax ginseng Asian ginseng (root) ## Red ginseng Red ginseng (Korean=홍삼, Template:Zh-st), is Panax ginseng that has been heated, either through steaming or sun-drying. It is frequently marinated in an herbal brew which results in the root becoming extremely brittle. This version of ginseng is traditionally associated with stimulating sexual function and increasing energy. Red ginseng is always produced from cultivated roots, usually from either China or South Korea. In 2002, a preliminary double-blind, crossover study of Korean red ginseng's effects on impotence reported that it can be an effective alternative for treating male erectile dysfunction.[15] A study shows that Red ginseng reduces the relapse of gastric cancer versus control[16] A study of ginseng's effects on rats show that while both White ginseng and Red ginseng reduce the incidence of cancer, the effects appear to be greater with Red ginseng.[17] Falcarinol, a seventeen-carbon diyne fatty alcohol was isolated from carrot and red ginseng, shown to have potent anticancer properties on primary mammary epithelial (breast cancer) cells.[18] Other acetylenic fatty alcohols in ginseng (panaxacol, panaxydol, panaxytriol) have antibiotic properties.[19] ## Wild ginseng Wild ginseng is ginseng that has not been planted and cultivated domestically, rather it is that which grows naturally and is harvested from wherever it is found to be growing. It is considered to be superior to field farmed ginseng by various authorities, and it has been shown to contain higher levels of ginsenoside. Wild ginseng is relatively rare and even increasingly endangered, due in large part to high demand for the product in recent years, which has led to the wild plants being sought out and harvested faster than new ones can grow (it requires years for a ginseng root to reach maturity). Wild ginseng can be either Asian or American and can be processed to be red ginseng. There are woods grown American ginseng programs in Maine, Tennessee, Virginia and North Carolina. [20][21] and United Plant Savers has been encouraging the woods planting of ginseng both to restore natural habitats and to remove pressure from any remaining wild ginseng, and they offer both advice and sources of rootlets. Woods grown plants have comparable value to wild grown ginseng of similar age. ## Ginseng alternatives These mostly adaptogenic plants are sometimes referred to as ginsengs, but they are either from a different family or genus. Only Jiaogulan actually contains ginsenosides, although ginsenosides alone do not determine the effectiveness of ginseng. Since each of these plants have different uses, one should research their properties before using. Descriptions and differentiation can be found in David Winston and Steven Maimes book Adaptogens[22] - Gynostemma pentaphyllum (Southern ginseng, aka Jiaogulan) - Eleutherococcus senticosus (Siberian ginseng) - Pseudostellaria heterophylla (Prince ginseng) - Withania somnifera (Indian ginseng, aka Ashwagandha) - Pfaffia paniculata (Brazilian ginseng) - Lepidium meyenii (Peruvian ginseng, aka Maca) Other plants which are referred to as ginsengs may not be adaptogens (although notoginseng is in the Panax family): - Angelica sinensis (Female ginseng, aka Dong Quai) - Panax notoginseng (San qi, hemostatic ingredient in Yunnan Bai Yao)	https://www.wikidoc.org/index.php/Ginseng
f7d145eb3e18e7798e9fba56b6780efdcf3a1dad	wikidoc	Glottis	Glottis The space between the vocal cords is called the glottis. # Function As the vocal cords vibrate, the resulting vibration produces a "buzzing" quality to the speech, called voice or voicing. Sound production involving only the glottis is called glottal. English has a voiceless glottal fricative spelled "h". In many accents of English the glottal stop (made by pressing the folds together) is used as a variant allophone of the phoneme Template:IPA (and in some dialects, occasionally of Template:IPA and Template:IPA); in some languages, this sound is a phoneme of its own. Skilled players of the Australian didgeridoo restrict their glottal opening in order to produce the full range of timbres available on the instrument. The vibration produced is an essential component of voiced consonants as well as vowels. If the vocal folds are drawn apart, air flows between them causing no vibration, as in the production of voiceless consonants. - Voiced consonants include Template:IPA - Voiceless consonants include Template:IPA # Additional images - Larynx - The entrance to the larynx, viewed from behind. - The entrance to the larynx.	Glottis Template:Infobox Anatomy The space between the vocal cords is called the glottis. # Function As the vocal cords vibrate, the resulting vibration produces a "buzzing" quality to the speech, called voice or voicing. Sound production involving only the glottis is called glottal. English has a voiceless glottal fricative spelled "h". In many accents of English the glottal stop (made by pressing the folds together) is used as a variant allophone of the phoneme Template:IPA (and in some dialects, occasionally of Template:IPA and Template:IPA); in some languages, this sound is a phoneme of its own. Skilled players of the Australian didgeridoo restrict their glottal opening in order to produce the full range of timbres available on the instrument. [1] The vibration produced is an essential component of voiced consonants as well as vowels. If the vocal folds are drawn apart, air flows between them causing no vibration, as in the production of voiceless consonants. - Voiced consonants include Template:IPA - Voiceless consonants include Template:IPA # Additional images - Larynx - The entrance to the larynx, viewed from behind. - The entrance to the larynx.	https://www.wikidoc.org/index.php/Glottic
b1ae32c52d5055aca2e66b3d906286740b0aaf5e	wikidoc	Glycine	Glycine Glycine (abbreviated as Gly or G) is an organic compound with the formula NH2CH2COOH. With only two hydrogen atoms as its 'side chain', glycine is the smallest of the 20 amino acids commonly found in proteins. Its codons are GGU, GGC, GGA, GGG. Glycine is a colourless, sweet-tasting crystalline solid. It is unique among the proteinogenic amino acids in that it is not chiral. It can fit into hydrophilic or hydrophobic environments, due to its two hydrogen atom side chain. # Production and key properties Glycine was discovered in 1820, by Henri Braconnot who boiled gelatin with sulfuric acid. Glycine is manufactured industrially by treating chloroacetic acid with ammonia: About 15M kg are produced annually in this way. In the USA (by GEO Specialty Chemicals, Inc.) and in Japan (by Shoadenko), glycine is produced via the Strecker amino acid synthesis. There are two producers of glycine in the United States. Chattem Chemicals, Inc., purchased by Sun Pharmaceutical, who is an international pharmaceutical company based in Mumbai, India and GEO Specialty Chemicals, Inc., who purchased the glycine and naphthalene sulfonate production facilities of Dow/Hampshire Chemical Corp. Chattem's manufacturing process ("MCA" process) occurs in batches and results in a finished product with some residual chloride but no sulfate, while GEO’s manufacturing process is considered a semi-batch process and results in a finished product with some residual sulfate but no chloride. Its pK values are 2.35 and 9.78, so above pH 9.78, most of the glycine exists as the anionic amine, H2NCH2CO2-. Below pH 2.35, its solutions contain mostly the cationic carboxylic acid H3N+CH2CO2H. Its isoelectric point (pI) is 6.06. # Biosynthesis Glycine is not essential to the human diet, as it is biosynthesized in the body from the amino acid serine, which is in turn derived from 3-phosphoglycerate. In most organisms, the enzyme Serine hydroxymethyltransferase catalyses this transformation via the cofactor pyridoxal phosphate: In the liver of vertebrates, glycine synthesis is catalyzed by glycine synthase (also called glycine cleavage enzyme). This conversion is readily reversible: Glycine is coded by codons GGU, GGC, GGA and GGG. Most proteins incorporate only small quantities of glycine. A notable exception is collagen, which contains about 35% glycine. # Degradation Glycine is degraded via three pathways. The predominant pathway in animals involves the catalysis of glycine cleavage enzyme, the same enzyme also involved in the biosynthesis of glycine. The degradation pathway is the reverse of this synthetic pathway: In the second pathway, glycine is degraded in two steps. The first step is the reverse of glycine biosynthesis from serine with serine hydroxymethyl transferase. Serine is then converted to pyruvate by serine dehydratase. In the third pathway of glycine degradation, glycine is converted to glyoxylate by D-amino acid oxidase. Glyoxylate is then oxidized by hepatic lactate dehydrogenase to oxalate in an NAD+-dependent reaction. # Physiological function The principal function of glycine is as a precursor to proteins. It is also a building block to numerous natural products. ## As a biosynthetic intermediate In higher eukaryotes, D-Aminolevulinic acid, the key precursor to porphyrins, is biosynthesized from glycine and succinyl-CoA. Glycine provides the central C2N subunit of all purines. ## As a neurotransmitter Glycine is an inhibitory neurotransmitter in the central nervous system, especially in the spinal cord, brainstem, and retina. When glycine receptors are activated, chloride enters the neuron via ionotropic receptors, causing an Inhibitory postsynaptic potential (IPSP). Strychnine is a strong antagonist at ionotropic glycine receptors, whereas bicuculline is a weak one. Glycine is a required co-agonist along with glutamate for NMDA receptors. In contrast to the inhibitory role of glycine in the spinal cord, this behaviour is facilitated at the (NMDA) glutaminergic receptors which are excitatory. The Template:LD50 of glycine is 7930 mg/kg in rats (oral), and it usually causes death by hyperexcitability. # Commercial uses In the US, glycine is typically sold in two grades: United States Pharmacopeia (“USP”), and technical grade. Most glycine is manufactured as USP grade material for diverse uses. USP grade sales account for approximately 80 to 85 percent of the U.S. market for glycine. - Pharmaceutical grade glycine is produced for some pharmaceutical applications, such as intravenous injections, where the customer’s purity requirements often exceed the minimum required under the USP grade designation. Pharmaceutical grade glycine is often produced to proprietary specifications and is typically sold at a premium over USP grade glycine. - Technical grade glycine, which may or may not meet USP grade standards, is sold for use in industrial applications; e.g., as an agent in metal complexing and finishing. Technical grade glycine is typically sold at a discount to USP grade glycine. ## Animal and human foods Other markets for USP grade glycine include its use an additive in pet food and animal feed. For humans, glycine is sold as a sweetener/taste enhancer. Food supplements and protein drinks contain glycine. Certain drug formulations include glycine to improve gastric absorption of the drug. ## Cosmetics and miscellaneous applications Glycine serves as a buffering agent in antacids, analgesics, antiperspirants, cosmetics, and toiletries. Many miscellaneous products use glycine or its derivatives, such as the production of rubber sponge products, fertilizers, metal complexants. ## Chemical feedstock Glycine is an intermediate in the synthesis of a variety of chemical products. It is used in the manufacture of the herbicide Glyphosate. Glyphosate (N-(phosphonomethyl) glycine) is a non-selective systemic herbicide used to kill weeds, especially perennials and broadcast or used in the cut-stump treatment as a forestry herbicide. Initially, Glyphosate was sold only by Monsanto under the Monsanto tradename Roundup, but is no longer under patent. # Presence in space The detection of glycine in the interstellar medium has been debated. In 2008, the glycine-like molecule aminoacetonitrile was discovered in the Large Molecule Heimat, a giant gas cloud near the galactic center in the constellation Sagittarius by the Max Planck Institute for Radio Astronomy. In 2009, glycine sampled in 2004 from comet Wild 2 by the NASA spacecraft Stardust was confirmed, the first discovery of extraterrestrial glycine. That mission's results bolstered the theory of panspermia, which claims that the "seeds" of life are widespread throughout the universe.	Glycine Glycine (abbreviated as Gly or G)[2] is an organic compound with the formula NH2CH2COOH. With only two hydrogen atoms as its 'side chain', glycine is the smallest of the 20 amino acids commonly found in proteins. Its codons are GGU, GGC, GGA, GGG. Glycine is a colourless, sweet-tasting crystalline solid. It is unique among the proteinogenic amino acids in that it is not chiral. It can fit into hydrophilic or hydrophobic environments, due to its two hydrogen atom side chain. # Production and key properties Glycine was discovered in 1820, by Henri Braconnot who boiled gelatin with sulfuric acid.[3] Glycine is manufactured industrially by treating chloroacetic acid with ammonia:[4] About 15M kg are produced annually in this way.[5] In the USA (by GEO Specialty Chemicals, Inc.) and in Japan (by Shoadenko), glycine is produced via the Strecker amino acid synthesis.[6] There are two producers of glycine in the United States. Chattem Chemicals, Inc., purchased by Sun Pharmaceutical, who is an international pharmaceutical company based in Mumbai, India and GEO Specialty Chemicals, Inc., who purchased the glycine and naphthalene sulfonate production facilities of Dow/Hampshire Chemical Corp.[6][7] Chattem's manufacturing process ("MCA" process) occurs in batches and results in a finished product with some residual chloride but no sulfate, while GEO’s manufacturing process is considered a semi-batch process and results in a finished product with some residual sulfate but no chloride. Its pK values are 2.35 and 9.78, so above pH 9.78, most of the glycine exists as the anionic amine, H2NCH2CO2-. Below pH 2.35, its solutions contain mostly the cationic carboxylic acid H3N+CH2CO2H. Its isoelectric point (pI) is 6.06. # Biosynthesis Glycine is not essential to the human diet, as it is biosynthesized in the body from the amino acid serine, which is in turn derived from 3-phosphoglycerate. In most organisms, the enzyme Serine hydroxymethyltransferase catalyses this transformation via the cofactor pyridoxal phosphate:[8] In the liver of vertebrates, glycine synthesis is catalyzed by glycine synthase (also called glycine cleavage enzyme). This conversion is readily reversible:[8] Glycine is coded by codons GGU, GGC, GGA and GGG. Most proteins incorporate only small quantities of glycine. A notable exception is collagen, which contains about 35% glycine.[8] # Degradation Glycine is degraded via three pathways. The predominant pathway in animals involves the catalysis of glycine cleavage enzyme, the same enzyme also involved in the biosynthesis of glycine. The degradation pathway is the reverse of this synthetic pathway:[8] In the second pathway, glycine is degraded in two steps. The first step is the reverse of glycine biosynthesis from serine with serine hydroxymethyl transferase. Serine is then converted to pyruvate by serine dehydratase.[8] In the third pathway of glycine degradation, glycine is converted to glyoxylate by D-amino acid oxidase. Glyoxylate is then oxidized by hepatic lactate dehydrogenase to oxalate in an NAD+-dependent reaction.[8] # Physiological function The principal function of glycine is as a precursor to proteins. It is also a building block to numerous natural products. ## As a biosynthetic intermediate In higher eukaryotes, D-Aminolevulinic acid, the key precursor to porphyrins, is biosynthesized from glycine and succinyl-CoA. Glycine provides the central C2N subunit of all purines.[8] ## As a neurotransmitter Glycine is an inhibitory neurotransmitter in the central nervous system, especially in the spinal cord, brainstem, and retina. When glycine receptors are activated, chloride enters the neuron via ionotropic receptors, causing an Inhibitory postsynaptic potential (IPSP). Strychnine is a strong antagonist at ionotropic glycine receptors, whereas bicuculline is a weak one. Glycine is a required co-agonist along with glutamate for NMDA receptors. In contrast to the inhibitory role of glycine in the spinal cord, this behaviour is facilitated at the (NMDA) glutaminergic receptors which are excitatory.[citation needed] The Template:LD50 of glycine is 7930 mg/kg in rats (oral),[9] and it usually causes death by hyperexcitability. # Commercial uses In the US, glycine is typically sold in two grades: United States Pharmacopeia (“USP”), and technical grade. Most glycine is manufactured as USP grade material for diverse uses. USP grade sales account for approximately 80 to 85 percent of the U.S. market for glycine. - Pharmaceutical grade glycine is produced for some pharmaceutical applications, such as intravenous injections, where the customer’s purity requirements often exceed the minimum required under the USP grade designation. Pharmaceutical grade glycine is often produced to proprietary specifications and is typically sold at a premium over USP grade glycine. - Technical grade glycine, which may or may not meet USP grade standards, is sold for use in industrial applications; e.g., as an agent in metal complexing and finishing. Technical grade glycine is typically sold at a discount to USP grade glycine.[10] ## Animal and human foods Other markets for USP grade glycine include its use an additive in pet food and animal feed. For humans, glycine is sold as a sweetener/taste enhancer. Food supplements and protein drinks contain glycine. Certain drug formulations include glycine to improve gastric absorption of the drug. ## Cosmetics and miscellaneous applications Glycine serves as a buffering agent in antacids, analgesics, antiperspirants, cosmetics, and toiletries. Many miscellaneous products use glycine or its derivatives, such as the production of rubber sponge products, fertilizers, metal complexants.[11] ## Chemical feedstock Glycine is an intermediate in the synthesis of a variety of chemical products. It is used in the manufacture of the herbicide Glyphosate. Glyphosate (N-(phosphonomethyl) glycine) is a non-selective systemic herbicide used to kill weeds, especially perennials and broadcast or used in the cut-stump treatment as a forestry herbicide. Initially, Glyphosate was sold only by Monsanto under the Monsanto tradename Roundup, but is no longer under patent. # Presence in space The detection of glycine in the interstellar medium has been debated.[12] In 2008, the glycine-like molecule aminoacetonitrile was discovered in the Large Molecule Heimat, a giant gas cloud near the galactic center in the constellation Sagittarius by the Max Planck Institute for Radio Astronomy.[13] In 2009, glycine sampled in 2004 from comet Wild 2 by the NASA spacecraft Stardust was confirmed, the first discovery of extraterrestrial glycine. That mission's results bolstered the theory of panspermia, which claims that the "seeds" of life are widespread throughout the universe.[14]	https://www.wikidoc.org/index.php/Glycine
9c81d0bb9dc96d76934697e45b379bc0f602e9d0	wikidoc	Granite	Granite Granite (Template:PronEng) is a common and widely occurring type of intrusive, felsic, igneous rock. Granite has a medium to coarse texture, occasionally with some individual crystals larger than the groundmass forming a rock known as porphyry. Granites can be pink to dark gray or even black, depending on their chemistry and mineralogy. Outcrops of granite tend to form tors, and rounded massifs. Granites sometimes occur in circular depressions surrounded by a range of hills, formed by the metamorphic aureole or hornfels. Granite is nearly always massive (lacking internal structures), hard and tough, and therefore it has gained widespread use as a construction stone. The average density of granite is 2.75 g/cm3. The word granite comes from the Latin granum, a grain, in reference to the coarse-grained structure of such a crystalline rock. # Mineralogy Granite is classified according to the QAPF diagram for coarse grained plutonic rocks (granitoids) and is named according to the percentage of quartz, alkali feldspar (orthoclase, sanidine, or microcline) and plagioclase feldspar on the A-Q-P half of the diagram. Granite-like rocks which are silica-undersaturated may have a feldspathoid such as nepheline, and are classified on the A-F-P half of the diagram. True granite according to modern petrologic convention contains both plagioclase and alkali feldspars. When a granitoid is devoid or nearly devoid of plagioclase the rock is referred to as alkali granite. When a granitoid contains <10% orthoclase it is called tonalite; pyroxene and amphibole are common in tonalite. A granite containing both muscovite and biotite micas is called a binary or two-mica granite. Two-mica granites are typically high in potassium and low in plagioclase, and are usually S-type granites or A-type granites. The volcanic equivalent of plutonic granite is rhyolite. ## Chemical composition A worldwide average of the average proportion of the different chemical components in granites, in descending order by weight percent, is: - SiO2 — 72.04% - Al2O3 — 14.42% - K2O — 4.12% - Na2O — 3.69% - CaO — 1.82% - FeO — 1.68% - Fe2O3 — 1.22% - MgO — 0.71% - TiO2 — 0.30% - P2O5 — 0.12% - MnO — 0.05% Based on 2485 analyses # Occurrence Granite is currently known only on Earth where it forms a major part of continental crust. Granite often occurs as relatively small, less than 100 km² stock masses (stocks) and in batholiths that are often associated with -rogenic mountain ranges. Small dikes of granitic composition called aplites are often associated with the margins of granitic intrusions. In some locations very coarse-grained pegmatite masses occur with granite. Granite has been intruded into the crust of the Earth during all geologic periods, although much of it is of Precambrian age. Granitic rock is widely distributed throughout the continental crust of the Earth and is the most abundant basement rock that underlies the relatively thin sedimentary veneer of the continents. Despite being fairly common throughout the world, the areas with the most commercial granite quarries are located in Finland, Norway and Sweden (Bohuslän), northern Portugal in Chaves and Vila Pouca de Aguiar, Spain (mostly Galicia and Extremadura), Brazil, India and several countries in southern Africa, namely Angola, Namibia, Zimbabwe and South Africa. # Origin Granite is an igneous rock and is formed from magma. Granitic magma has many potential origins but it must intrude other rocks. Most granite intrusions are emplaced at depth within the crust, usually greater than 1.5 kilometres and up to 50 km depth within thick continental crust. The origin of granite is contentious and has led to varied schemes of classification. Classification schemes are regional; there is a French scheme, a British scheme and an American scheme. This confusion arises because the classification schemes define granite by different means. Generally the 'alphabet-soup' classification is used because it classifies based on genesis or origin of the magma. ## Geochemical origins Granitoids are a ubiquitous component of the crust. They have crystallized from magmas that have compositions at or near a eutectic point (or a temperature minimum on a cotectic curve). Magmas will evolve to the eutectic because of igneous differentiation, or because they represent low degrees of partial melting. Fractional crystallisation serves to reduce a melt in iron, magnesium, titanium, calcium and sodium, and enrich the melt in potassium and silicon - alkali feldspar (rich in potassium) and quartz (SiO2), are two of the defining constituents of granite. This process operates regardless of the origin of the parental magma to the granite, and regardless of its chemistry. However, the composition and origin of the magma which differentiates into granite, leaves certain geochemical and mineralogical evidence as to what the granite's parental rock was. The final mineralogy, texture and chemical composition of a granite is often distinctive as to its origin. For instance, a granite which is formed from melted sediments may have more alkali feldspar, whereas a granite derived from melted basalt may be richer in plagioclase feldspar. It is on this basis that the modern "alphabet" classification schemes are based. ## Alphabet soup classification The 'alphabet soup' scheme of Chappell & White was proposed initially to divide granites into I-type granite (or igneous protolith) granite and S-type or sedimentary protolith granite. Both of these types of granite are formed by melting of high grade metamorphic rocks, either other granite or intrusive mafic rocks, or buried sediment, respectively. M-type or mantle derived granite was proposed later, to cover those granites which were clearly sourced from crystallised mafic magmas, generally sourced from the mantle. These are rare, because it is difficult to turn basalt into granite via fractional crystallisation. A-type or anorogenic granites are formed above volcanic "hot spot" activity and have peculiar mineralogy and geochemistry. These granites are formed by melting of the lower crust under conditions that are usually extremely dry. The rhyolites of the Yellowstone caldera are examples of volcanic equivalents of A-type granite. ## Granitization An old, and largely discounted theory, granitization states that granite is formed in place by extreme metasomatism by fluids bringing in elements e.g. potassium and removing others e.g. calcium to transform the metamorphic rock into a granite. This was supposed to occur across a migrating front. The production of granite by metamorphic heat is difficult, but is observed to occur in certain amphibolite and granulite terrains. In-situ granitisation or melting by metamorphism is difficult to recognise except where leucosome and melanosome textures are present in gneisses. Once a metamorphic rock is melted it is no longer a metamorphic rock and is a magma, so these rocks are seen as a transitional between the two, but are not technically granite as they do not actually intrude into other rocks. In all cases, melting of solid rock requires high temperature, and also water or other volatiles which act as a catalyst by lowering the solidus temperature of the rock. # Ascent and emplacement The ascent and emplacement of large volumes of granite within the upper continental crust is a source of much debate amongst geologists. There is a lack of field evidence for any proposed mechanisms, so hypotheses are predominantly based upon experimental data. There are two major hypotheses for the ascent of magma through the crust: - Stokes Diapir - Fracture Propagation Of these two mechanisms, Stokes diapir was favoured for many years in the absence of a reasonable alternative. The basic idea is that magma will rise through the crust as a single mass through buoyancy. As it rises it heats the wall rocks, causing them to behave as a power-law fluid and thus flow around the pluton allowing it to pass rapidly and without major heat loss (Weinberg, 1994). This is entirely feasible in the warm, ductile lower crust where rocks are easily deformed, but runs into problems in the upper crust which is far colder and more brittle. Rocks there do not deform so easily: for magma to rise as a pluton it would expend far too much energy in heating wall rocks, thus cooling and solidifying before reaching higher levels within the crust. Nowadays fracture propagation is the mechanism preferred by many geologists as it largely eliminates the major problems of moving a huge mass of magma through cold brittle crust. Magma rises instead in small channels along self-propagating dykes which form along new or pre-existing fault systems and networks of active shear zones (Clemens, 1998). As these narrow conduits open, the first magma to enter solidifies and provides a form of insulation for later magma. Granitic magma must make room for itself or be intruded into other rocks in order to form an intrusion, and several mechanisms have been proposed to explain how large batholiths have been emplaced: - Stoping, where the granite cracks the wall rocks and pushes upwards as it removes blocks of the overlying crust - Assimilation, where the granite melts its way up into the crust and removes overlying material in this way - Inflation, where the granite body inflates under pressure and is injected into position Most geologists today accept that a combination of these phenomena can be used to explain granite intrusions, and that not all granites can be explained entirely by one or another mechanism. # Natural Radiation Granite is a normal, geological source of radiation in the natural environment. Granite contains around 10 to 20 parts per million of uranium. By contrast, more mafic rocks such as tonalite, gabbro or diorite have 1 to 5 ppm uranium, and limestones and sedimentary rocks usually have equally low amounts. Many large granite plutons are the sources for palaeochannel-hosted or roll front uranium ore deposits, where the uranium washes into the sediments from the granite uplands and associated, often highly radioactive, pegmatites. Granite could be considered a potential natural radiological hazard as, for instance, villages located over granite may be susceptible to higher doses of radiation than other communities. Cellars and basements sunk into soils formed over or from particularly uraniferous granites can become a trap for radon gas, which is heavier than air. However, in the majority of cases, although granite is a significant source of natural radiation as compared to other rocks it is not often an acute health threat or significant risk factor. Various resources from national geological survey organisations are accessible online to assist in assessing the risk factors in granite country and design rules relating, in particular, to preventing accumulation of radon gas in enclosed basements and dwellings. # Uses ## Antiquity The Red Pyramid of Egypt (c.26th century BC), named for the light crimson hue of its exposed granite surfaces, is the third largest of Egyptian pyramids. Menkaure's Pyramid, likely dating to the same era, was constructed of limestone and granite blocks. The Great Pyramid of Giza (c.2580 BC) contains a huge granite sarcophagus fashioned of "Red Aswan Granite." The mostly ruined Black Pyramid dating from the reign of Amenemhat III once had a polished granite pyramidion or capstone, now on display in the main hall of the Egyptian Museum in Cairo (see Dahshur). Other uses in Ancient Egypt, include columns, door lintels, sills, jambs, and wall and floor veneer. How the Egyptians worked the solid granite is still a matter of debate. Dr. Patrick Hunt has postulated that the Egyptians used emery shown to have higher hardness on the Mohs scale. Many large Hindu temples in southern India, particularly those built by the 11th century king Rajaraja Chola I, were made of granite. There is a large amount of granite in these structures. They are comparable to the Great Pyramid of Giza. ## Modern Granite has been extensively used as a dimension stone and as flooring tiles in public and commercial buildings and monuments. Because of its abundance granite was commonly used as to build foundations for homes in New England. The Granite Railway, America's first railroad, was built to haul granite from the quarries in Quincy, Massachusetts, to the Neponset River for transport. With increasing amounts of acid rain in parts of the world, granite has begun to supplant marble as a monument material, since it is much more durable. Polished granite is also a popular choice for kitchen countertops due to its high durability and aesthetic qualities. - Azul Noche (Spain) Azul Noche (Spain) - Santa Cecelia (Brazil) Santa Cecelia (Brazil) - Gran Violet (Brazil) Gran Violet (Brazil) - Lavanda Blue (Brazil) Lavanda Blue (Brazil) Engineers have traditionally used polished granite surfaces to establish a plane of reference, since they are relatively impervious and inflexible. Sandblasted concrete with a heavy aggregate content has an appearance similar to rough granite, and is often used as a substitute when use of real granite is impractical. A most unusual use of granite was in the construction of the rails for the Haytor Granite Tramway, Devon, England, in 1820. Curling stones are traditionally fashioned of Ailsa Craig granite. The first stones were made in the 1750s, the original source being Ailsa Craig in Scotland. Because of the particular rarity of the granite, the best stones can cost as much as US$1,500. Between 60–70 percent of the stones used today are made from Ailsa Craig granite, although the island is now a wildlife reserve and is no longer used for quarrying. # Rock climbing Granite is one of the rocks most prized by climbers, for its steepness, soundness, crack systems, and friction. Well-known venues for granite climbing include Yosemite, the Bugaboos, the Mont Blanc massif (and peaks such as the Aiguille du Dru, the Aiguille du Midi and the Grandes Jorasses), the Bregaglia, Corsica, parts of the Karakoram, the Fitzroy Massif, Patagonia, Baffin Island, the Cornish coast and the Cairngorms. Granite rock climbing is so popular that many of the artificial rock climbing walls found in gyms and theme parks are made to look and feel like granite. Most, however, are made from manufactured materials, given the fact that granite is generally too heavy for portable rock climbing walls, as well as the buildings in which stationary walls are located.	Granite Template:Otheruses2 Granite (Template:PronEng) is a common and widely occurring type of intrusive, felsic, igneous rock. Granite has a medium to coarse texture, occasionally with some individual crystals larger than the groundmass forming a rock known as porphyry. Granites can be pink to dark gray or even black, depending on their chemistry and mineralogy. Outcrops of granite tend to form tors, and rounded massifs. Granites sometimes occur in circular depressions surrounded by a range of hills, formed by the metamorphic aureole or hornfels. Granite is nearly always massive (lacking internal structures), hard and tough, and therefore it has gained widespread use as a construction stone. The average density of granite is 2.75 g/cm3. The word granite comes from the Latin granum, a grain, in reference to the coarse-grained structure of such a crystalline rock. # Mineralogy Granite is classified according to the QAPF diagram for coarse grained plutonic rocks (granitoids) and is named according to the percentage of quartz, alkali feldspar (orthoclase, sanidine, or microcline) and plagioclase feldspar on the A-Q-P half of the diagram. Granite-like rocks which are silica-undersaturated may have a feldspathoid such as nepheline, and are classified on the A-F-P half of the diagram. True granite according to modern petrologic convention contains both plagioclase and alkali feldspars. When a granitoid is devoid or nearly devoid of plagioclase the rock is referred to as alkali granite. When a granitoid contains <10% orthoclase it is called tonalite; pyroxene and amphibole are common in tonalite. A granite containing both muscovite and biotite micas is called a binary or two-mica granite. Two-mica granites are typically high in potassium and low in plagioclase, and are usually S-type granites or A-type granites. The volcanic equivalent of plutonic granite is rhyolite. ## Chemical composition A worldwide average of the average proportion of the different chemical components in granites, in descending order by weight percent, is:[1] - SiO2 — 72.04% - Al2O3 — 14.42% - K2O — 4.12% - Na2O — 3.69% - CaO — 1.82% - FeO — 1.68% - Fe2O3 — 1.22% - MgO — 0.71% - TiO2 — 0.30% - P2O5 — 0.12% - MnO — 0.05% Based on 2485 analyses # Occurrence Granite is currently known only on Earth where it forms a major part of continental crust. Granite often occurs as relatively small, less than 100 km² stock masses (stocks) and in batholiths that are often associated with orogenic mountain ranges. Small dikes of granitic composition called aplites are often associated with the margins of granitic intrusions. In some locations very coarse-grained pegmatite masses occur with granite. Granite has been intruded into the crust of the Earth during all geologic periods, although much of it is of Precambrian age. Granitic rock is widely distributed throughout the continental crust of the Earth and is the most abundant basement rock that underlies the relatively thin sedimentary veneer of the continents. Despite being fairly common throughout the world, the areas with the most commercial granite quarries are located in Finland, Norway and Sweden (Bohuslän), northern Portugal in Chaves and Vila Pouca de Aguiar, Spain (mostly Galicia and Extremadura), Brazil, India and several countries in southern Africa, namely Angola, Namibia, Zimbabwe and South Africa. # Origin Granite is an igneous rock and is formed from magma. Granitic magma has many potential origins but it must intrude other rocks. Most granite intrusions are emplaced at depth within the crust, usually greater than 1.5 kilometres and up to 50 km depth within thick continental crust. The origin of granite is contentious and has led to varied schemes of classification. Classification schemes are regional; there is a French scheme, a British scheme and an American scheme. This confusion arises because the classification schemes define granite by different means. Generally the 'alphabet-soup' classification is used because it classifies based on genesis or origin of the magma. ## Geochemical origins Granitoids are a ubiquitous component of the crust. They have crystallized from magmas that have compositions at or near a eutectic point (or a temperature minimum on a cotectic curve). Magmas will evolve to the eutectic because of igneous differentiation, or because they represent low degrees of partial melting. Fractional crystallisation serves to reduce a melt in iron, magnesium, titanium, calcium and sodium, and enrich the melt in potassium and silicon - alkali feldspar (rich in potassium) and quartz (SiO2), are two of the defining constituents of granite. This process operates regardless of the origin of the parental magma to the granite, and regardless of its chemistry. However, the composition and origin of the magma which differentiates into granite, leaves certain geochemical and mineralogical evidence as to what the granite's parental rock was. The final mineralogy, texture and chemical composition of a granite is often distinctive as to its origin. For instance, a granite which is formed from melted sediments may have more alkali feldspar, whereas a granite derived from melted basalt may be richer in plagioclase feldspar. It is on this basis that the modern "alphabet" classification schemes are based. ## Alphabet soup classification The 'alphabet soup' scheme of Chappell & White was proposed initially to divide granites into I-type granite (or igneous protolith) granite and S-type or sedimentary protolith granite[2]. Both of these types of granite are formed by melting of high grade metamorphic rocks, either other granite or intrusive mafic rocks, or buried sediment, respectively. M-type or mantle derived granite was proposed later, to cover those granites which were clearly sourced from crystallised mafic magmas, generally sourced from the mantle. These are rare, because it is difficult to turn basalt into granite via fractional crystallisation. A-type or anorogenic granites are formed above volcanic "hot spot" activity and have peculiar mineralogy and geochemistry. These granites are formed by melting of the lower crust under conditions that are usually extremely dry. The rhyolites of the Yellowstone caldera are examples of volcanic equivalents of A-type granite.[3] [4] ## Granitization An old, and largely discounted theory, granitization states that granite is formed in place by extreme metasomatism by fluids bringing in elements e.g. potassium and removing others e.g. calcium to transform the metamorphic rock into a granite. This was supposed to occur across a migrating front. The production of granite by metamorphic heat is difficult, but is observed to occur in certain amphibolite and granulite terrains. In-situ granitisation or melting by metamorphism is difficult to recognise except where leucosome and melanosome textures are present in gneisses. Once a metamorphic rock is melted it is no longer a metamorphic rock and is a magma, so these rocks are seen as a transitional between the two, but are not technically granite as they do not actually intrude into other rocks. In all cases, melting of solid rock requires high temperature, and also water or other volatiles which act as a catalyst by lowering the solidus temperature of the rock. # Ascent and emplacement The ascent and emplacement of large volumes of granite within the upper continental crust is a source of much debate amongst geologists. There is a lack of field evidence for any proposed mechanisms, so hypotheses are predominantly based upon experimental data. There are two major hypotheses for the ascent of magma through the crust: - Stokes Diapir - Fracture Propagation Of these two mechanisms, Stokes diapir was favoured for many years in the absence of a reasonable alternative. The basic idea is that magma will rise through the crust as a single mass through buoyancy. As it rises it heats the wall rocks, causing them to behave as a power-law fluid and thus flow around the pluton allowing it to pass rapidly and without major heat loss (Weinberg, 1994). This is entirely feasible in the warm, ductile lower crust where rocks are easily deformed, but runs into problems in the upper crust which is far colder and more brittle. Rocks there do not deform so easily: for magma to rise as a pluton it would expend far too much energy in heating wall rocks, thus cooling and solidifying before reaching higher levels within the crust. Nowadays fracture propagation is the mechanism preferred by many geologists as it largely eliminates the major problems of moving a huge mass of magma through cold brittle crust. Magma rises instead in small channels along self-propagating dykes which form along new or pre-existing fault systems and networks of active shear zones (Clemens, 1998)[5]. As these narrow conduits open, the first magma to enter solidifies and provides a form of insulation for later magma. Granitic magma must make room for itself or be intruded into other rocks in order to form an intrusion, and several mechanisms have been proposed to explain how large batholiths have been emplaced: - Stoping, where the granite cracks the wall rocks and pushes upwards as it removes blocks of the overlying crust - Assimilation, where the granite melts its way up into the crust and removes overlying material in this way - Inflation, where the granite body inflates under pressure and is injected into position Most geologists today accept that a combination of these phenomena can be used to explain granite intrusions, and that not all granites can be explained entirely by one or another mechanism. # Natural Radiation Granite is a normal, geological source of radiation in the natural environment. Granite contains around 10 to 20 parts per million of uranium. By contrast, more mafic rocks such as tonalite, gabbro or diorite have 1 to 5 ppm uranium, and limestones and sedimentary rocks usually have equally low amounts. Many large granite plutons are the sources for palaeochannel-hosted or roll front uranium ore deposits, where the uranium washes into the sediments from the granite uplands and associated, often highly radioactive, pegmatites. Granite could be considered a potential natural radiological hazard as, for instance, villages located over granite may be susceptible to higher doses of radiation than other communities.[6] Cellars and basements sunk into soils formed over or from particularly uraniferous granites can become a trap for radon gas, which is heavier than air. However, in the majority of cases, although granite is a significant source of natural radiation as compared to other rocks it is not often an acute health threat or significant risk factor. Various resources from national geological survey organisations are accessible online to assist in assessing the risk factors in granite country and design rules relating, in particular, to preventing accumulation of radon gas in enclosed basements and dwellings. # Uses ## Antiquity The Red Pyramid of Egypt (c.26th century BC), named for the light crimson hue of its exposed granite surfaces, is the third largest of Egyptian pyramids. Menkaure's Pyramid, likely dating to the same era, was constructed of limestone and granite blocks. The Great Pyramid of Giza (c.2580 BC) contains a huge granite sarcophagus fashioned of "Red Aswan Granite." The mostly ruined Black Pyramid dating from the reign of Amenemhat III once had a polished granite pyramidion or capstone, now on display in the main hall of the Egyptian Museum in Cairo (see Dahshur). Other uses in Ancient Egypt,[7] include columns, door lintels, sills, jambs, and wall and floor veneer. How the Egyptians worked the solid granite is still a matter of debate. Dr. Patrick Hunt[8] has postulated that the Egyptians used emery shown to have higher hardness on the Mohs scale. Many large Hindu temples in southern India, particularly those built by the 11th century king Rajaraja Chola I, were made of granite. There is a large amount of granite in these structures. They are comparable to the Great Pyramid of Giza.[9] ## Modern Granite has been extensively used as a dimension stone and as flooring tiles in public and commercial buildings and monuments. Because of its abundance granite was commonly used as to build foundations for homes in New England. The Granite Railway, America's first railroad, was built to haul granite from the quarries in Quincy, Massachusetts, to the Neponset River for transport. With increasing amounts of acid rain in parts of the world, granite has begun to supplant marble as a monument material, since it is much more durable. Polished granite is also a popular choice for kitchen countertops due to its high durability and aesthetic qualities. - Azul Noche (Spain) Azul Noche (Spain) - Santa Cecelia (Brazil) Santa Cecelia (Brazil) - Gran Violet (Brazil) Gran Violet (Brazil) - Lavanda Blue (Brazil) Lavanda Blue (Brazil) Engineers have traditionally used polished granite surfaces to establish a plane of reference, since they are relatively impervious and inflexible. Sandblasted concrete with a heavy aggregate content has an appearance similar to rough granite, and is often used as a substitute when use of real granite is impractical. A most unusual use of granite was in the construction of the rails for the Haytor Granite Tramway, Devon, England, in 1820. Curling stones are traditionally fashioned of Ailsa Craig granite. The first stones were made in the 1750s, the original source being Ailsa Craig in Scotland. Because of the particular rarity of the granite, the best stones can cost as much as US$1,500. Between 60–70 percent of the stones used today are made from Ailsa Craig granite, although the island is now a wildlife reserve and is no longer used for quarrying.[10] # Rock climbing Granite is one of the rocks most prized by climbers, for its steepness, soundness, crack systems, and friction. Well-known venues for granite climbing include Yosemite, the Bugaboos, the Mont Blanc massif (and peaks such as the Aiguille du Dru, the Aiguille du Midi and the Grandes Jorasses), the Bregaglia, Corsica, parts of the Karakoram, the Fitzroy Massif, Patagonia, Baffin Island, the Cornish coast and the Cairngorms. Granite rock climbing is so popular that many of the artificial rock climbing walls found in gyms and theme parks are made to look and feel like granite. Most, however, are made from manufactured materials, given the fact that granite is generally too heavy for portable rock climbing walls, as well as the buildings in which stationary walls are located.	https://www.wikidoc.org/index.php/Granite
213b46703437bc4cdba6e16a00f834d9f9bf1916	wikidoc	Guanine	Guanine # Overview Guanine is one of the five main nucleobases found in the nucleic acids DNA and RNA; the others being adenine, cytosine, thymine, and uracil. With the formula C5H5N5O, guanine is a derivative of purine, consisting of a fused pyrimidine-imidazole ring system with conjugated double bonds. Being unsaturated, the bicyclic molecule is planar. The guanine nucleoside is called guanosine. # Basic principles Guanine, along with adenine and cytosine, is present in both DNA and RNA, whereas thymine is usually seen only in DNA and uracil only in RNA. Guanine has two tautomeric forms, the keto form and enol form. It binds to cytosine through three hydrogen bonds. In cytosine, the amino group acts as the hydrogen donor and the C-2 carbonyl and the N-3 amine as the hydrogen-bond acceptors. Guanine has a group at C-6 that acts as the hydrogen acceptor, while the group at N-1 and the amino group at C-2 acts as the hydrogen donors. # Isolation, background, & some chemistry The first isolation of guanine was reported in 1844 from the excreta of sea birds, known as guano, which was used as a source of fertilizer. About fifty years later, Fischer determined the structure and also showed that uric acid can be converted to guanine. The first complete synthesis was done by Traube and remains among the best large-scale preparations. Guanine can be hydrolyzed with strong acid to glycine, ammonia, carbon dioxide, and carbon monoxide at 180°C. Guanine oxidizes more readily than adenine, the other purine-derivative base in DNA and RNA. Its high melting point of 350°C reflects the intermolecular hydrogen bonding between the oxo and amino groups in the molecules in the crystal. Because of this intermolecular bonding, guanine is relatively insoluble in water, although it is soluble in dilute acids and bases. # Syntheses Trace amounts of guanine form by the polymerization of ammonium cyanide (NH4CN). Two experiments conducted by Levy et al., showed that heating 10 M NH4CN at 80°C for 24 hours gave a yield of 0.0007% while using 0.1 M NH4CN frozen at -20°C for 25 years gave a 0.0035% yield. These results indicate guanine could arise in frozen regions of the primitive earth. In 1984, Yuasa reported a 0.00017% yield of guanine after the electrical discharge of NH3, CH4, C2H6, and 50 mL of water, followed by a subsequent acid hydrolysis. However, it is unknown if the presence of guanine was not simply resulted from a contaminant of the reaction. A Fischer-Tropsch synthesis can also be used to form guanine, along with adenine, uracil and thymine. Heating an equimolar gas mixture of CO, H2, and NH3 to 700 °C for 0.24 to 0.4 hours, followed by quick cooling and then sustainted reheating to 100-200°C for 16-44 hours with an alumina catalyst yielded guanine and uracil: Traube's synthesis involves heating 2,4,5-triamino-1,6-dihydro-6-oxypyrimidine (as the sulphate) with formic acid for several hours. # Other uses In 1656 in Paris, François Jaquin (a rosary maker) extracted from scales of some fishes the so called pearl essence, crystalline guanine forming G-quadruplexes: in cosmetic industry, crystalline guanine is used as an additive to various products (e.g., shampoos), where it provides the pearly iridescent effect. It is also used in metallic paints and simulated pearls and plastics. It provides shimmering lustre to eye shadow and nail polish. Guanine crystals are rhombic platelets composed of multiple, transparent layers but they have a high index of refraction that partially reflects and transmits light from layer to layer thus producing a pearly luster. It can be applied by spray, painting or dipping. It may irritate eyes. Its alternatives are mica, synthetic pearl, and aluminium and bronze particles.	Guanine Template:Chembox new # Overview Guanine is one of the five main nucleobases found in the nucleic acids DNA and RNA; the others being adenine, cytosine, thymine, and uracil. With the formula C5H5N5O, guanine is a derivative of purine, consisting of a fused pyrimidine-imidazole ring system with conjugated double bonds. Being unsaturated, the bicyclic molecule is planar. The guanine nucleoside is called guanosine. # Basic principles Guanine, along with adenine and cytosine, is present in both DNA and RNA, whereas thymine is usually seen only in DNA and uracil only in RNA. Guanine has two tautomeric forms, the keto form and enol form. It binds to cytosine through three hydrogen bonds. In cytosine, the amino group acts as the hydrogen donor and the C-2 carbonyl and the N-3 amine as the hydrogen-bond acceptors. Guanine has a group at C-6 that acts as the hydrogen acceptor, while the group at N-1 and the amino group at C-2 acts as the hydrogen donors. # Isolation, background, & some chemistry The first isolation of guanine was reported in 1844 from the excreta of sea birds, known as guano, which was used as a source of fertilizer. About fifty years later, Fischer determined the structure and also showed that uric acid can be converted to guanine. The first complete synthesis was done by Traube and remains among the best large-scale preparations. Guanine can be hydrolyzed with strong acid to glycine, ammonia, carbon dioxide, and carbon monoxide at 180°C. Guanine oxidizes more readily than adenine, the other purine-derivative base in DNA and RNA. Its high melting point of 350°C reflects the intermolecular hydrogen bonding between the oxo and amino groups in the molecules in the crystal. Because of this intermolecular bonding, guanine is relatively insoluble in water, although it is soluble in dilute acids and bases. # Syntheses Trace amounts of guanine form by the polymerization of ammonium cyanide (NH4CN). Two experiments conducted by Levy et al., showed that heating 10 M NH4CN at 80°C for 24 hours gave a yield of 0.0007% while using 0.1 M NH4CN frozen at -20°C for 25 years gave a 0.0035% yield. These results indicate guanine could arise in frozen regions of the primitive earth. In 1984, Yuasa reported a 0.00017% yield of guanine after the electrical discharge of NH3, CH4, C2H6, and 50 mL of water, followed by a subsequent acid hydrolysis. However, it is unknown if the presence of guanine was not simply resulted from a contaminant of the reaction. A Fischer-Tropsch synthesis can also be used to form guanine, along with adenine, uracil and thymine. Heating an equimolar gas mixture of CO, H2, and NH3 to 700 °C for 0.24 to 0.4 hours, followed by quick cooling and then sustainted reheating to 100-200°C for 16-44 hours with an alumina catalyst yielded guanine and uracil: Traube's synthesis involves heating 2,4,5-triamino-1,6-dihydro-6-oxypyrimidine (as the sulphate) with formic acid for several hours. # Other uses In 1656 in Paris, François Jaquin (a rosary maker) extracted from scales of some fishes the so called pearl essence, crystalline guanine forming G-quadruplexes: in cosmetic industry, crystalline guanine is used as an additive to various products (e.g., shampoos), where it provides the pearly iridescent effect. It is also used in metallic paints and simulated pearls and plastics. It provides shimmering lustre to eye shadow and nail polish. Guanine crystals are rhombic platelets composed of multiple, transparent layers but they have a high index of refraction that partially reflects and transmits light from layer to layer thus producing a pearly luster. It can be applied by spray, painting or dipping. It may irritate eyes. Its alternatives are mica, synthetic pearl, and aluminium and bronze particles.	https://www.wikidoc.org/index.php/Guanine
4cf6b94ee08bd9214f150cf75173d86ed25ee770	wikidoc	Guarana	Guarana Guarana (Brazilian name guaraná) (Template:IPA2, Template:IPA or Template:IPA), Paullinia cupana (syn. P. crysan, P. sorbilis), is a climbing plant in the Sapindaceae family, native to the Amazon basin. While guarana features large leaves and clusters of flowers, it is best known for its fruit, which is about the size of a coffee berry. Each fruit contains about one seed, which contains approximately three times more caffeine than coffee beans. Caffeine is a stimulant of the central nervous system, cardiac muscle, as well as the respiratory system. The guarana fruit's color ranges from orange to red and contains black seeds which are partly covered by white arils. The color contrast when the fruit has been split open has been likened to eyeballs; this has formed the basis of a myth. # History and culture The word guarana comes from the Portuguese guaraná, which has its origins in the Sateré-Mawé language word warana. Guarana plays an important role in Tupi and Guaraní Brazilian culture. According to a myth dating back to the Sateré-Maué tribe, guarana's domestication originated with a deity killing a beloved village child. In order to console the villagers, a more benevolent god plucked the left eye from the child and planted it in the forest, resulting in the wild variety of guarana. The god then plucked the right eye from the child and planted it in the village, giving rise to domesticated guarana. The Guarinís would make this tea by shelling and washing the seeds, followed by pounding them into a fine powder. The powder is kneaded into a dough and then shaped into cylinders. This product is known as guarana bread or Brazilian cocoa, which would be grated and then immersed into hot water along with sugar. This plant was introduced to western civilization in the 17th century following its discovery by Father Felip Betendorf. By 1958, guarana was commercialized. # Uses Guarana is used in soft drinks (such as Bawls), where it is sweetened and then carbonated. It is also used in pure form in energy shots such as SuddenRush Guarana. Additionally, it is used as an ingredient in herbal tea and made into capsules. Oftentimes, guarana is marketed as a unique stimulant, distinct from caffeine; this is to take advantage of the fact that not many consumers are aware that caffeine is found in a wide variety of plants. In general, South America obtains most of its caffeine from guarana. ## Beverages Brazil, which consumes the third-most amount of soft drinks in the world, produces several brands of soft drink from guarana extract. In fact, sales of guarana drinks in Brazil are even greater than that of cola drinks. They claim that the consumption of guarana does not result in jitters associated with the consumption of coffee. However this may be a placebo effect or result from the presence of additional substances. ## Other uses Studies involving guarana show benefits to cognitive function. These studies have not been evaluated by the Food and Drug Administration or any similar government agencies. In the United States, guarana holds a GRAS-status, i.e. generally regarded as safe. The Journal of Human Nutrition and Dietetics published a study in June 2001 showing an average 11.2 pound weight loss in a group taking a mixture of yerba mate, guarana, and damiana, compared to an average 1 pound loss in a placebo group after 45 days. Although side-effects of guarana are rare, drugs.com recommends: "when considering the use of herbal supplements, consultation with a primary health care professional is advisable. Additionally, consultation with a practitioner trained in the uses of herbal/health supplements may be beneficial, and coordination of treatment among all health care providers involved may be advantageous". Drugs.com also advises not to mix guarana with ephedrine. # Effects A study in Brazil of guarana extract showed an aggregation decrease in rabbit platelets of up to 37% below control values and a decrease of platelet thromboxane formation from arachidonic acid of up to 78% below control values, again in rabbits. It is not known if such platelet action has any effect in heart attack or ischemic stroke risk reduction. The science is very preliminary and at best 'hypothesis generating' and needs to be expanded in order to show actual clinical benefit in humans, if any. A 1997 study of guarana's effects on the physical activity of rats showed increased memory retention and physical endurance when compared with a placebo. Other studies have shown antioxidant, antibacterial, and fat cell reduction (when combined with conjugated linoleic acid) properties in guarana. # Composition These are the chemicals that are found in the guarana plant: The chemical guaranine is identical to caffeine derived from other sources, for example coffee, tea, and mate. Guaranine, theine, and mateine are all official synonyms for caffeine. # Footnotes - ↑ Jump up to: 1.0 1.1 1.2 1.3 Bennett Alan Weinberg, and Bonnie K.Bealer, The World of Caffeine: The Science and Culture of the World's Most Popular Drug (New York: Routledge, 2001) 259-60 - ↑ Bennett Alan Weinberg, and Bonnie K.Bealer, The World of Caffeine: The Science and Culture of the World's Most Popular Drug (New York: Routledge, 2001) 280 - ↑ Sir Ghillean Prance, Mark Nesbitt (2004). Cultural History of Plants. New York: Routledge. p. 179..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} - ↑ "guarana". Merriam Webster. Retrieved 2007-09-18. - ↑ Hans T. Beck, "10 Caffeine, Alcohol, and Sweeteners," Cultural History of Plants, ed. Sir Ghillean Prance and Mark Nesbitt (New York: Routledge, 2004) 179 - ↑ Jump up to: 6.0 6.1 Bennett Alan Weinberg, and Bonnie K.Bealer, The World of Caffeine: The Science and Culture of the World's Most Popular Drug (New York: Routledge, 2001) 230 - ↑ Bennett Alan Weinberg, and Bonnie K. Bealer, The World of Caffeine: The Science and Culture of the World's Most Popular Drug (New York: Routledge, 2001) 192-3 - ↑ Matt Moffett and Nikhil Deogun, The Wall Street Journal. "Guarana's potent reputation makes consumers drink it up". Standard-Times. Retrieved 2007-09-18. - ↑ Haskell; et al. (2006). "A double-blind, placebo-controlled, multi-dose evaluation of the acute behavioural effects of guarana in humans". J Psychopharmacol. PMID 16533867.CS1 maint: Explicit use of et al. (link) - ↑ "Energy Drinks" (PDF). University of California, Davis". April 2007. Retrieved 2007-09-18. - ↑ Anderson, T and Foght, J (2001). "Weight loss and delayed gastric emptying following a South American herbal preparation in overweight patients". J Hum Nutr Diet. 14 (3): 243.CS1 maint: Multiple names: authors list (link) - ↑ "guarana". Drugs.com. Retrieved 2007-09-19. - ↑ Bydlowski SP; et al. (1991). "An aqueous extract of guarana (Paullinia cupana) decreases platelet thromboxane synthesis". Braz J Med Biol Res. 24 (4): 421–4.CS1 maint: Explicit use of et al. (link) - ↑ Nicolaou, KC; et al. (1979). "Synthesis and biological properties of pinane-thromboxane A2, a selective inhibitor of coronary artery constriction, platelet aggregation, and thromboxane formation". Proc. Natl. Acad. Sci. USA. 76 (6): 2566–2570. PMID 288046.CS1 maint: Explicit use of et al. (link) - ↑ Espinola EB; et al. (1997). "Pharmacological activity of Guarana (Paullinia cupana Mart.) in laboratory animals". J Ethnopharmacol. 55 (3): 223–9.CS1 maint: Explicit use of et al. (link) - ↑ Terpstra; et al. (2002). "The Decrease in Body Fat in Mice Fed Conjugated Linoleic Acid Is Due to Increases in Energy Expenditure and Energy Loss in the Excreta". J Nutr. 132: 940–945.CS1 maint: Explicit use of et al. (link) - ↑ "Guarana". Dr. Duke's Phytochemical and Ethnobotanical Databases. 2007-09-18. Retrieved 2007-09-18. - ↑ Duke, James A. 1992. Handbook of phytochemical constituents of GRAS herbs and other economic plants. Boca Raton, FL. CRC Press. - ↑ "Caffeine". Biological Magnetic Resonance Data Bank, University of Wisconsin-Madison. Retrieved 2007-09-19.	Guarana Guarana (Brazilian name guaraná) (Template:IPA2, Template:IPA or Template:IPA), Paullinia cupana (syn. P. crysan, P. sorbilis), is a climbing plant in the Sapindaceae family, native to the Amazon basin. While guarana features large leaves and clusters of flowers, it is best known for its fruit, which is about the size of a coffee berry. Each fruit contains about one seed, which contains approximately three times more caffeine than coffee beans.[1] Caffeine is a stimulant of the central nervous system, cardiac muscle, as well as the respiratory system.[2] The guarana fruit's color ranges from orange to red and contains black seeds which are partly covered by white arils. The color contrast when the fruit has been split open has been likened to eyeballs; this has formed the basis of a myth.[3] # History and culture The word guarana comes from the Portuguese guaraná, which has its origins in the Sateré-Mawé language word warana.[4] Guarana plays an important role in Tupi and Guaraní Brazilian culture. According to a myth dating back to the Sateré-Maué tribe, guarana's domestication originated with a deity killing a beloved village child. In order to console the villagers, a more benevolent god plucked the left eye from the child and planted it in the forest, resulting in the wild variety of guarana. The god then plucked the right eye from the child and planted it in the village, giving rise to domesticated guarana.[5] The Guarinís would make this tea by shelling and washing the seeds, followed by pounding them into a fine powder. The powder is kneaded into a dough and then shaped into cylinders. This product is known as guarana bread or Brazilian cocoa, which would be grated and then immersed into hot water along with sugar.[1] This plant was introduced to western civilization in the 17th century following its discovery by Father Felip Betendorf. By 1958, guarana was commercialized.[1] # Uses Guarana is used in soft drinks (such as Bawls), where it is sweetened and then carbonated. It is also used in pure form in energy shots such as SuddenRush Guarana. Additionally, it is used as an ingredient in herbal tea and made into capsules. Oftentimes, guarana is marketed as a unique stimulant, distinct from caffeine; this is to take advantage of the fact that not many consumers are aware that caffeine is found in a wide variety of plants.[1] In general, South America obtains most of its caffeine from guarana.[6] ## Beverages Template:Seealso Brazil, which consumes the third-most amount of soft drinks in the world,[7] produces several brands of soft drink from guarana extract. In fact, sales of guarana drinks in Brazil are even greater than that of cola drinks.[8] They claim that the consumption of guarana does not result in jitters associated with the consumption of coffee. However this may be a placebo effect or result from the presence of additional substances.[6] ## Other uses Studies involving guarana show benefits to cognitive function.[9] These studies have not been evaluated by the Food and Drug Administration or any similar government agencies. In the United States, guarana holds a GRAS-status, i.e. generally regarded as safe.[10] The Journal of Human Nutrition and Dietetics published a study in June 2001 showing an average 11.2 pound weight loss in a group taking a mixture of yerba mate, guarana, and damiana, compared to an average 1 pound loss in a placebo group after 45 days.[11] Although side-effects of guarana are rare, drugs.com recommends: "when considering the use of herbal supplements, consultation with a primary health care professional is advisable. Additionally, consultation with a practitioner trained in the uses of herbal/health supplements may be beneficial, and coordination of treatment among all health care providers involved may be advantageous". Drugs.com also advises not to mix guarana with ephedrine.[12] # Effects A study in Brazil of guarana extract showed an aggregation decrease in rabbit platelets of up to 37% below control values and a decrease of platelet thromboxane formation from arachidonic acid of up to 78% below control values, again in rabbits.[13] It is not known if such platelet action has any effect in heart attack or ischemic stroke risk reduction.[14] The science is very preliminary and at best 'hypothesis generating' and needs to be expanded in order to show actual clinical benefit in humans, if any. A 1997 study of guarana's effects on the physical activity of rats showed increased memory retention and physical endurance when compared with a placebo.[15] Other studies have shown antioxidant, antibacterial, and fat cell reduction (when combined with conjugated linoleic acid) properties in guarana.[16] # Composition These are the chemicals that are found in the guarana plant:[17][18] The chemical guaranine is identical to caffeine derived from other sources, for example coffee, tea, and mate. Guaranine, theine, and mateine are all official synonyms for caffeine.[19] # Footnotes - ↑ Jump up to: 1.0 1.1 1.2 1.3 Bennett Alan Weinberg, and Bonnie K.Bealer, The World of Caffeine: The Science and Culture of the World's Most Popular Drug (New York: Routledge, 2001) 259-60 - ↑ Bennett Alan Weinberg, and Bonnie K.Bealer, The World of Caffeine: The Science and Culture of the World's Most Popular Drug (New York: Routledge, 2001) 280 - ↑ Sir Ghillean Prance, Mark Nesbitt (2004). Cultural History of Plants. New York: Routledge. p. 179..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} - ↑ "guarana". Merriam Webster. Retrieved 2007-09-18. - ↑ Hans T. Beck, "10 Caffeine, Alcohol, and Sweeteners," Cultural History of Plants, ed. Sir Ghillean Prance and Mark Nesbitt (New York: Routledge, 2004) 179 - ↑ Jump up to: 6.0 6.1 Bennett Alan Weinberg, and Bonnie K.Bealer, The World of Caffeine: The Science and Culture of the World's Most Popular Drug (New York: Routledge, 2001) 230 - ↑ Bennett Alan Weinberg, and Bonnie K. Bealer, The World of Caffeine: The Science and Culture of the World's Most Popular Drug (New York: Routledge, 2001) 192-3 - ↑ Matt Moffett and Nikhil Deogun, The Wall Street Journal. "Guarana's potent reputation makes consumers drink it up". Standard-Times. Retrieved 2007-09-18. - ↑ Haskell; et al. (2006). "A double-blind, placebo-controlled, multi-dose evaluation of the acute behavioural effects of guarana in humans". J Psychopharmacol. PMID 16533867.CS1 maint: Explicit use of et al. (link) - ↑ "Energy Drinks" (PDF). University of California, Davis". April 2007. Retrieved 2007-09-18. - ↑ Anderson, T and Foght, J (2001). "Weight loss and delayed gastric emptying following a South American herbal preparation in overweight patients". J Hum Nutr Diet. 14 (3): 243.CS1 maint: Multiple names: authors list (link) - ↑ "guarana". Drugs.com. Retrieved 2007-09-19. - ↑ Bydlowski SP; et al. (1991). "An aqueous extract of guarana (Paullinia cupana) decreases platelet thromboxane synthesis". Braz J Med Biol Res. 24 (4): 421–4.CS1 maint: Explicit use of et al. (link) - ↑ Nicolaou, KC; et al. (1979). "Synthesis and biological properties of pinane-thromboxane A2, a selective inhibitor of coronary artery constriction, platelet aggregation, and thromboxane formation". Proc. Natl. Acad. Sci. USA. 76 (6): 2566–2570. PMID 288046.CS1 maint: Explicit use of et al. (link) - ↑ Espinola EB; et al. (1997). "Pharmacological activity of Guarana (Paullinia cupana Mart.) in laboratory animals". J Ethnopharmacol. 55 (3): 223–9.CS1 maint: Explicit use of et al. (link) - ↑ Terpstra; et al. (2002). "The Decrease in Body Fat in Mice Fed Conjugated Linoleic Acid Is Due to Increases in Energy Expenditure and Energy Loss in the Excreta". J Nutr. 132: 940–945.CS1 maint: Explicit use of et al. (link) - ↑ "Guarana". Dr. Duke's Phytochemical and Ethnobotanical Databases. 2007-09-18. Retrieved 2007-09-18. - ↑ Duke, James A. 1992. Handbook of phytochemical constituents of GRAS herbs and other economic plants. Boca Raton, FL. CRC Press. - ↑ "Caffeine". Biological Magnetic Resonance Data Bank, University of Wisconsin-Madison. Retrieved 2007-09-19. # External links - Raintree Tropical Plant Database: Guaraná - Guarana at Duke's database - Guarana at USDA database bg:Гуарана ca:Guaranà cs:Guarana de:Guaraná it:Paullinia cupana he:גוארנה ka:გუარანა nl:Guarana simple:Guarana sr:Гварана fi:Guarana sv:Guarana Template:WikiDoc Sources	https://www.wikidoc.org/index.php/Guarana
b0866a9870b9dd3c944ece87b42ceea98eb34113	wikidoc	Gunnera	Gunnera Gunnera is a genus of herbaceous flowering plants, some of them gigantic. The genus is the only member of the family Gunneraceae. The 40-50 species vary enormously in leaf size. Gunnera manicata, native to the Serra do Mar mountains of southeastern Brazil, is perhaps the largest species, with leaves typically 1.5-2 m (5-6 ft) wide, but exceptionally long, up to 3.4 m (11 ft), borne on thick, succulent leaf stalks (petioles) up to 2.5 m (8 ft) long. It germinates best in very moist, but not wet, conditions and temperatures of 22 to 29 °C. Only slightly smaller is G. masafuerae of the Juan Fernandez Islands off the Chilean coast. They can have leaves up to 2.9 m (9 ft 5 inches) in width on stout leaf stalks 1.5 m (5 ft) long and 11 cm (4.5 in) thick according to Skottsberg. On nearby Isla Más Afuera, G. peltata frequently has an upright trunk to 5.5 m (18 ft) in height by 25–30 cm (10–12 in) thick, bearing leaves up to 2 m (6 ft 4 inches) wide. G. magnifica of the Colombian Andes bears the largest leaf buds of any plant; up to 60 cm (2 ft) long and 40 cm (16 inches) thick. The succulent leaf stalks are up to 2.7 m (8 ft 10 inches) long. The massive inflorescence of small, reddish flowers is up to 2.3 m (7 ft 6 inches) long and weighs about 13 kg. Other giant Gunnera species are found throughout the Neotropics and Hawaii. Several small species are found in New Zealand, notably G. albocarpa, with leaves only 1–2 cm long, and also in South America, with G. magellanica having leaves 5–9 cm wide on stalks 8–15 cm long. Commonly known as "giant rhubarb". This genus was named after the Norwegian botanist Johann Ernst Gunnerus. - Gunnera albocarpa - Gunnera arenaria - Gunnera densiflora - Gunnera dentata - Gunnera flavida - Gunnera hamiltonii - Gunnera kauaiensis - Gunnera magellanica - Gunnera magnifica - Gunnera manicata - Gunnera masafuerae - Gunnera monoica - Gunnera perpensa - Gunnera petaloïdea - Gunnera prorepens - Gunnera tinctoria # Cyanobacterial Symbiosis In nature, all Gunnera plants form a symbiosis with a nitrogen-fixing cyanobacteria, thought to be exclusively Nostoc punctiforme. The bacteria invade the plant via glands found at the base of each leaf stalk and initiate an intracellular symbiosis which is thought to provide the plant with fixed nitrogen in return for fixed carbon for the bacterium. This intracellular interaction is unique in higher plants and may provide insights to allow the creation of novel symbioses between crop plants and cyanobacteria, allowing growth in areas lacking fixed nitrogen in the soil. # Uses The stalks of G. tinctoria (nalcas) are edible. Their principal use is fresh consumption, but also they are prepared in salads, liquor or marmalade. Leaves of this species are used in covering curanto (a traditional Chilean food). Gunnera perpensa is used as a source of traditional medicine in Southern Africa.	Gunnera Gunnera is a genus of herbaceous flowering plants, some of them gigantic. The genus is the only member of the family Gunneraceae. The 40-50 species vary enormously in leaf size. Gunnera manicata, native to the Serra do Mar mountains of southeastern Brazil, is perhaps the largest species, with leaves typically 1.5-2 m (5-6 ft) wide, but exceptionally long, up to 3.4 m (11 ft), borne on thick, succulent leaf stalks (petioles) up to 2.5 m (8 ft) long. It germinates best in very moist, but not wet, conditions and temperatures of 22 to 29 °C. Only slightly smaller is G. masafuerae of the Juan Fernandez Islands off the Chilean coast. They can have leaves up to 2.9 m (9 ft 5 inches) in width on stout leaf stalks 1.5 m (5 ft) long and 11 cm (4.5 in) thick according to Skottsberg. On nearby Isla Más Afuera, G. peltata frequently has an upright trunk to 5.5 m (18 ft) in height by 25–30 cm (10–12 in) thick, bearing leaves up to 2 m (6 ft 4 inches) wide. G. magnifica of the Colombian Andes bears the largest leaf buds of any plant; up to 60 cm (2 ft) long and 40 cm (16 inches) thick. The succulent leaf stalks are up to 2.7 m (8 ft 10 inches) long. The massive inflorescence of small, reddish flowers is up to 2.3 m (7 ft 6 inches) long and weighs about 13 kg. Other giant Gunnera species are found throughout the Neotropics and Hawaii. Several small species are found in New Zealand, notably G. albocarpa, with leaves only 1–2 cm long, and also in South America, with G. magellanica having leaves 5–9 cm wide on stalks 8–15 cm long. Commonly known as "giant rhubarb". This genus was named after the Norwegian botanist Johann Ernst Gunnerus. - Gunnera albocarpa - Gunnera arenaria - Gunnera densiflora - Gunnera dentata - Gunnera flavida - Gunnera hamiltonii - Gunnera kauaiensis - Gunnera magellanica - Gunnera magnifica - Gunnera manicata - Gunnera masafuerae - Gunnera monoica - Gunnera perpensa - Gunnera petaloïdea - Gunnera prorepens - Gunnera tinctoria ## Cyanobacterial Symbiosis In nature, all Gunnera plants form a symbiosis with a nitrogen-fixing cyanobacteria, thought to be exclusively Nostoc punctiforme. The bacteria invade the plant via glands found at the base of each leaf stalk[1] and initiate an intracellular symbiosis which is thought to provide the plant with fixed nitrogen in return for fixed carbon for the bacterium. This intracellular interaction is unique in higher plants and may provide insights to allow the creation of novel symbioses between crop plants and cyanobacteria, allowing growth in areas lacking fixed nitrogen in the soil. ## Uses The stalks of G. tinctoria (nalcas) are edible. Their principal use is fresh consumption, but also they are prepared in salads, liquor or marmalade. Leaves of this species are used in covering curanto (a traditional Chilean food). Gunnera perpensa is used as a source of traditional medicine in Southern Africa.	https://www.wikidoc.org/index.php/Gunnera
6b6a3bf2569252fda3b9349e2ab8c07f212ddfa1	wikidoc	HLA-A29	HLA-A29 HLA-A29 (A29) is an HLA-A serotype. The serotype identifies the more common HLA-A29 gene products. A29 is a split antigen of the A19 broad antigen serotype group. It is similar to the antigens A30, A31, A32, A33, and A74. A31 is more common in Japan, Siberia and Indigenous Americans. It is also more frequent in NE Europe than SW Europe. # Serotype # A29 Allele frequencies ### A2902 # A29-B Haplotypes A29-Cw16-B44(A2902:Cw1601:B4403) appears to have originated in West Africa were Cw16 frequency is highest and had undergone more linkage equilibrium. Cw16 decline slowly heading north and more rapidly to the east and northeast, with the highest frequency/latitude north generally along Eastern Spain into the British Ilses, some flow up the channel but haplotype frequency drops in the interior of Europe. This haplotype can generally be extended from A- to -DQ as A29-Cw16-B44-DR7-DQ2.2: A2901 : Cw1601 : B4403 : DRB10701 : DQA10201 : DQB1*0202 And, the Cw16 component is in strong linkage disequilibrium with the DR7-DQ2.2 component suggesting that since the haplotypes introduction into Europe there has not been adequate time for equilibration, supporting its recent introduction into Europe. This particular haplotype supports theories of migration that are more numerous than those supported by mtDNA or Y chromosomal information, many such 'smaller' migrations are evident with HLA haplotypes, suggesting a much greater complexity to human population than haploid loci make evident.	HLA-A29 HLA-A29 (A29) is an HLA-A serotype. The serotype identifies the more common HLA-A29 gene products. A29 is a split antigen of the A19 broad antigen serotype group. It is similar to the antigens A30, A31, A32, A33, and A74. A31 is more common in Japan, Siberia and Indigenous Americans. It is also more frequent in NE Europe than SW Europe. # Serotype # A29 Allele frequencies ### A2902 # A29-B Haplotypes A29-Cw16-B44(A2902:Cw1601:B4403) appears to have originated in West Africa were Cw16 frequency is highest and had undergone more linkage equilibrium. Cw16 decline slowly heading north and more rapidly to the east and northeast, with the highest frequency/latitude north generally along Eastern Spain into the British Ilses, some flow up the channel but haplotype frequency drops in the interior of Europe. This haplotype can generally be extended from A- to -DQ as A29-Cw16-B44-DR7-DQ2.2: A2901 : Cw1601 : B4403 : DRB10701 : DQA10201 : DQB1*0202 And, the Cw16 component is in strong linkage disequilibrium with the DR7-DQ2.2 component suggesting that since the haplotypes introduction into Europe there has not been adequate time for equilibration, supporting its recent introduction into Europe. This particular haplotype supports theories of migration that are more numerous than those supported by mtDNA or Y chromosomal information, many such 'smaller' migrations are evident with HLA haplotypes, suggesting a much greater complexity to human population than haploid loci make evident.	https://www.wikidoc.org/index.php/HAL-A29
5ed799606a5fd8af16f98e21ab53f53539b832d1	wikidoc	HB plot	HB plot Knowledge of the relationship between protein’s structure and its dynamic behavior is essential for understanding protein function. The description of a protein three dimensional structure as a network of hydrogen bonding interactions (HB plot) was introduced as a tool for exploring protein structure and function. By analyzing the network of tertiary interactions the possible spread of information within a protein can be investigated. HB plot offers a simple way of analyzing protein secondary structure and tertiary structure. Hydrogen bonds stabilizing secondary structural elements (secondary hydrogen bonds) and those formed between distant amino acid residues - defined as tertiary hydrogen bonds - can be easily distinguished in HB plot, thus, amino acid residues involved in stabilizing protein structure and function can be identified. By analyzing the network of tertiary interactions the possible spread of information within a protein can be investigated as well. # Features The plot distinguishes between main chain-main chain, main chain-side chain and side chain-side chain hydrogen bonding interactions. Bifurcated hydrogen bonds and multiple hydrogen bonds between amino acid residues; and intra- and interchain hydrogen bonds are also indicated on the plots. Three classes of hydrogen bondings are distinguished by color coding; short (distance smaller than 2.5 A between donor and acceptor), intermediate (between 2.5 A and 3.2 A) and long hydrogen bonds (greater than 3.2 A). # Secondary structure elements in HB plot In representations of the HB plot characteristic patterns of secondary structure elements can be recognised easily. 1.) Helices can be identified as strips directly adjacent to the diagonal. 2.) Antiparallel beta sheets appear in HB plot as cross-diagonal. 3.) Parallel beta sheets appears in the HB plot as parallel to the diagional. 4.) Loops appear as breaks in the diagonal between the cross-diagonal beta-sheet motifs. # Examples of usage 1. The cytochrome P450s (P450s) are xenobiotic-metabolizing membrane-bound heme-containing enzymes that use molecular oxygen and electrons from NADPH cytochrome P450 reductase to oxidize their substrates. CYP2B4, a member of the cytochrome P450 family is the only protein within this family, whose X-Ray structure in both open 11 and closed form 12 is published. The comparison of the open and closed structures of CYP2B4 structures reveals large-scale conformational rearrangement between the two states, with the greatest conformational change around the residues 215-225, which is widely open in ligand-free state and shut after ligand binding; and the region around loop C near the heme. Examining the HB plot of the closed and open state of CYP2B4 revealed that the rearrangement of tertiary hydrogen bonds was in excellent agreement with the current knowledge of the cytochrome P450 catalytic cycle. The first step in P450 catalytic cycle is identified as substrate binding. Preliminary binding of a ligand near to the entrance breaks hydrogen bonds S212-E474, S207-H172 in the open form of CYP2B4 and hydrogen bonds E218-A102, Q215-L51 are formed that fix the entrance in the closed form as the HB plot reveals. The second step is the transfer of the first electron from NADPH via an electron transfer chain. For the electron transfer a conformational change occurs that triggers interaction of the P450 with the NADPH cytochrome P450 reductase. Breaking of hydrogen bonds between S128-N287, S128-T291, L124-N287 and forming S96-R434, A116-R434, R125-I435, D82-R400 at the NADPH cytochrome P450 reductase binding site -as seen in HB plot- transform CYP2B4 to a conformation state, where binding of NADPH cytochrome P450 reductase occurs. In the third step oxygen enters CYP2B4 in the closed state - the state where newly formed hydrogen bonds S176-T300, H172-S304, N167-R308 open a tunnel which is exactly the size and shape of an oxygen molecule. 2. The lipocalin family is a large and diverse family of proteins with functions as small hydrophobic molecule transporters. Beta-lactoglobulin is a typical member of the lipocalin family. Beta-lactoglobulin was found to have a role in the transport of hydrophobic ligands such as retinol or fatty acids. Its crystal structure were determined with different ligands and in ligand-free form as well. The crystal structures determined so far reveal that tha typical lipocalin contains eight-stranded antiparallel-barrel arranged to form a conical central cavity in which the hydrophobic ligand is bound. The structure of beta-lactoglobulin reveals that the barrel form structure with the central cavity of the protein has an entrance surrounded by five beta-loops with centers around 26, 35, 63, 87 and 111, which suffer a conformational change during the ligand binding and close the cavity. The overall shape of beta lactoglobulin is characteristic of the lipocalin family. In the absence of alpha-helices, the main diagonal almost disappears and the cross-diagonals representing the beta-sheets dominate the plot. Relatively low number of tertiary hydrogen bonds can be found in the plot, with three high-density regions, one of which is connected to a loop at the residues around 63, a second is connected to the loop around 87, and a third region which is connected to the regions 26 and 35. The fifth loop around 111 is represented only one tertiary hydrogen bond in the HB plot. In the three-dimensional structure, tertiary hydrogen bonds are formed i, near to the entrance, directly involved in conformational rearrangement during ligand binding and ii, at the bottom of the ‘barrel’. HB plots of the open and closed forms of beta-lactoglobulin are very similar, all unique motifs can be recognized in both forms. Difference in HB plots of open and ligand-bound form show few important individual changes in tertiary hydrogen bonding pattern. Especially, the formation of hydrogen bonds between Y20-E157 and S21-H161 in closed form might be crucial in conformational rearrangement. These hydrogen bonds lie at the bottom of the cavity, which suggests that the closure of the entrance of a lipocalin starts when a ligand reached the bottom of the cavity and broke hydrogen bonds R123-Y99, R123-T18 and V41-Q120. Lipocalins are known to have very low sequence similarity with high structural similarity. The only conserved regions are exactly the region around 20 and 160 with unknown role.	HB plot Knowledge of the relationship between protein’s structure and its dynamic behavior is essential for understanding protein function. The description of a protein three dimensional structure as a network of hydrogen bonding interactions (HB plot) [1] was introduced as a tool for exploring protein structure and function. By analyzing the network of tertiary interactions the possible spread of information within a protein can be investigated. HB plot offers a simple way of analyzing protein secondary structure and tertiary structure. Hydrogen bonds stabilizing secondary structural elements (secondary hydrogen bonds) and those formed between distant amino acid residues - defined as tertiary hydrogen bonds - can be easily distinguished in HB plot, thus, amino acid residues involved in stabilizing protein structure and function can be identified. By analyzing the network of tertiary interactions the possible spread of information within a protein can be investigated as well. # Features The plot distinguishes between main chain-main chain, main chain-side chain and side chain-side chain hydrogen bonding interactions. Bifurcated hydrogen bonds and multiple hydrogen bonds between amino acid residues; and intra- and interchain hydrogen bonds are also indicated on the plots. Three classes of hydrogen bondings are distinguished by color coding; short (distance smaller than 2.5 A between donor and acceptor), intermediate (between 2.5 A and 3.2 A) and long hydrogen bonds (greater than 3.2 A). # Secondary structure elements in HB plot In representations of the HB plot characteristic patterns of secondary structure elements can be recognised easily. 1.) Helices can be identified as strips directly adjacent to the diagonal. 2.) Antiparallel beta sheets appear in HB plot as cross-diagonal. 3.) Parallel beta sheets appears in the HB plot as parallel to the diagional. 4.) Loops appear as breaks in the diagonal between the cross-diagonal beta-sheet motifs. # Examples of usage 1. The cytochrome P450s (P450s) are xenobiotic-metabolizing membrane-bound heme-containing enzymes that use molecular oxygen and electrons from NADPH cytochrome P450 reductase to oxidize their substrates. CYP2B4, a member of the cytochrome P450 family is the only protein within this family, whose X-Ray structure in both open 11 and closed form 12 is published. The comparison of the open and closed structures of CYP2B4 structures reveals large-scale conformational rearrangement between the two states, with the greatest conformational change around the residues 215-225, which is widely open in ligand-free state and shut after ligand binding; and the region around loop C near the heme. Examining the HB plot of the closed and open state of CYP2B4 revealed that the rearrangement of tertiary hydrogen bonds was in excellent agreement with the current knowledge of the cytochrome P450 catalytic cycle. The first step in P450 catalytic cycle is identified as substrate binding. Preliminary binding of a ligand near to the entrance breaks hydrogen bonds S212-E474, S207-H172 in the open form of CYP2B4 and hydrogen bonds E218-A102, Q215-L51 are formed that fix the entrance in the closed form as the HB plot reveals. The second step is the transfer of the first electron from NADPH via an electron transfer chain. For the electron transfer a conformational change occurs that triggers interaction of the P450 with the NADPH cytochrome P450 reductase. Breaking of hydrogen bonds between S128-N287, S128-T291, L124-N287 and forming S96-R434, A116-R434, R125-I435, D82-R400 at the NADPH cytochrome P450 reductase binding site -as seen in HB plot- transform CYP2B4 to a conformation state, where binding of NADPH cytochrome P450 reductase occurs. In the third step oxygen enters CYP2B4 in the closed state - the state where newly formed hydrogen bonds S176-T300, H172-S304, N167-R308 open a tunnel which is exactly the size and shape of an oxygen molecule. 2. The lipocalin family is a large and diverse family of proteins with functions as small hydrophobic molecule transporters. Beta-lactoglobulin is a typical member of the lipocalin family. Beta-lactoglobulin was found to have a role in the transport of hydrophobic ligands such as retinol or fatty acids. Its crystal structure were determined [e.g. Qin, 1998] with different ligands and in ligand-free form as well. The crystal structures determined so far reveal that tha typical lipocalin contains eight-stranded antiparallel-barrel arranged to form a conical central cavity in which the hydrophobic ligand is bound. The structure of beta-lactoglobulin reveals that the barrel form structure with the central cavity of the protein has an entrance surrounded by five beta-loops with centers around 26, 35, 63, 87 and 111, which suffer a conformational change during the ligand binding and close the cavity. The overall shape of beta lactoglobulin is characteristic of the lipocalin family. In the absence of alpha-helices, the main diagonal almost disappears and the cross-diagonals representing the beta-sheets dominate the plot. Relatively low number of tertiary hydrogen bonds can be found in the plot, with three high-density regions, one of which is connected to a loop at the residues around 63, a second is connected to the loop around 87, and a third region which is connected to the regions 26 and 35. The fifth loop around 111 is represented only one tertiary hydrogen bond in the HB plot. In the three-dimensional structure, tertiary hydrogen bonds are formed i, near to the entrance, directly involved in conformational rearrangement during ligand binding and ii, at the bottom of the ‘barrel’. HB plots of the open and closed forms of beta-lactoglobulin are very similar, all unique motifs can be recognized in both forms. Difference in HB plots of open and ligand-bound form show few important individual changes in tertiary hydrogen bonding pattern. Especially, the formation of hydrogen bonds between Y20-E157 and S21-H161 in closed form might be crucial in conformational rearrangement. These hydrogen bonds lie at the bottom of the cavity, which suggests that the closure of the entrance of a lipocalin starts when a ligand reached the bottom of the cavity and broke hydrogen bonds R123-Y99, R123-T18 and V41-Q120. Lipocalins are known to have very low sequence similarity with high structural similarity. The only conserved regions are exactly the region around 20 and 160 with unknown role.	https://www.wikidoc.org/index.php/HB_plot
4f8ec785caf12a29312349cccbc3434b23bcf689	wikidoc	HEPACAM	HEPACAM Gene HEPACAM, named based on its original site of identification - hepatocytes and the nature of its protein product - a cell adhesion molecule (CAM), was first discovered and characterised in human liver and reported by Shali Shen (MD, PhD) in 2005. The gene encodes a protein of 416 amino acids, designated as hepaCAM, which is a new member of the immunoglobulin superfamily of cell adhesion molecules (IgSF CAM). The main biological functions of hepaCAM include a) modulating cell-matrix adhesion and migration, and b) inhibiting cancer cell growth. (Note: HEPACAM, gene name; hepaCAM, protein name) # Discovery Through differential screening of gene expression, over 200 genes were found to be either up- or down-regulated in a hepatocellular carcinoma patient. These genes were subsequently evaluated against a panel of human HCC specimens, leading to the identification of a novel gene HEPN1. Based on the sequence of HEPN1, the new gene HEPACAM was then isolated and characterised. # Characteristics and functions Structurally, hepaCAM is a glycoprotein containing an extracellular domain with 2 Ig-like loops, a transmembrane region and a cytoplasmic domain. Matched to chromosome 11q24, gene HEPACAM is ubiquitously expressed in normal human tissues, with particularly high expression levels in the central nervous system (CNS), and is frequently suppressed in a variety of tumour types. Functionally, hepaCAM is involved in cell-extracellular matrix interactions and growth control of cancer cells, and is able to induce differentiation of glioblastoma cells. In cell signaling, hepaCAM directly interacts with F-actin and calveolin 1, and is capable of inducing senescence-like growth arrest via a p53/p21-dependent pathway. Moreover, hepaCAM is proteolystically cleaved near the transmemberane region. These findings indicate that the new Ig-like cell adhesion molecule hepaCAM is also a tumour suppressor. # Other names - glialCAM, which was cloned from a human brain cDNA library in 2008 and found to be identical to hepaCAM; and - HEPACAM1, when HEPACAM2 emerged in 2010. # About HEPACAM 2 Metastatic canine mammary carcinoma and their metastases are characterized by decreased HEPACAM2 but unchanged HEPACAM2 expression levels when compared to normal glands.	HEPACAM Gene HEPACAM, named based on its original site of identification - hepatocytes and the nature of its protein product - a cell adhesion molecule (CAM), was first discovered and characterised in human liver and reported by Shali Shen (MD, PhD) in 2005.[1] The gene encodes a protein of 416 amino acids, designated as hepaCAM, which is a new member of the immunoglobulin superfamily of cell adhesion molecules (IgSF CAM). The main biological functions of hepaCAM include a) modulating cell-matrix adhesion and migration, and b) inhibiting cancer cell growth.[1] (Note: HEPACAM, gene name; **hepaCAM, protein name) # Discovery Through differential screening of gene expression, over 200 genes were found to be either up- or down-regulated in a hepatocellular carcinoma patient. These genes were subsequently evaluated against a panel of human HCC specimens, leading to the identification of a novel gene HEPN1.[2] Based on the sequence of HEPN1, the new gene HEPACAM was then isolated and characterised.[3] # Characteristics and functions Structurally, hepaCAM is a glycoprotein containing an extracellular domain with 2 Ig-like loops, a transmembrane region and a cytoplasmic domain.[3] Matched to chromosome 11q24, gene HEPACAM is ubiquitously expressed in normal human tissues, with particularly high expression levels in the central nervous system (CNS), and is frequently suppressed in a variety of tumour types.[4] Functionally, hepaCAM is involved in cell-extracellular matrix interactions and growth control of cancer cells,[3] and is able to induce differentiation of glioblastoma cells.[5] In cell signaling, hepaCAM directly interacts with F-actin[6] and calveolin 1,[7] and is capable of inducing senescence-like growth arrest via a p53/p21-dependent pathway.[4] Moreover, hepaCAM is proteolystically cleaved near the transmemberane region.[8] These findings indicate that the new Ig-like cell adhesion molecule hepaCAM is also a tumour suppressor.[9] # Other names - glialCAM, which was cloned from a human brain cDNA library in 2008 and found to be identical to hepaCAM;[10] and - HEPACAM1, when HEPACAM2 emerged in 2010.[11] # About HEPACAM 2 Metastatic canine mammary carcinoma and their metastases are characterized by decreased HEPACAM2 but unchanged HEPACAM2 expression levels when compared to normal glands.[11]	https://www.wikidoc.org/index.php/HEPACAM
df765d576e5e8bad43a264d81a2821df618ab203	wikidoc	HIKESHI	HIKESHI HIKESHI is a protein important in lung and multicellular organismal development that, in humans, is encoded by the HIKESHI gene. HIKESHI is found on chromosome 11 in humans and chromosome 7 in mice. Similar sequences (orthologs) are found in most animal and fungal species. The mouse homolog, lethal gene on chromosome 7 Rinchik 6 protein is encoded by the l7Rn6 gene. When the l7Rn6 protein is disrupted in mice, the mice display severe emphysema at birth as a result of disorganization of the Golgi apparatus and formation of aberrant vesicular structures within club cells. # Gene HIKESHI is a protein-coding gene in Homo sapiens. Alternate names for the gene are FLJ43020, HSPC138, HSPC179, and L7RN6. Located on long arm of chromosome 11 at area q14.2, the entire gene including introns and exons is 42,698 base pairs on the plus strand. The mRNA of HIKESHI Variant 1 includes exons 1, 3, 4, 5, and 7 amounting to 1,183 base pairs, with base pairs 239 to 832 representing the coding regions. ## Alternative Splicing Variant 1 is the longest and most common protein coding variant. The three other main variants use an alternate exon sequence that throws off the reading frame, causing early termination of the mRNA sequence and undergoes protein decay. The table below shows the different variants and exon usage. The four variants shown in the table above are the most common isoforms found in human cells. There are a total of 13 alternatively spliced sequences and 3 unspliced forms that utilize two alternative promoters. The mRNA variants differ on the combination of 8 different exons, alternate, overlapping exons, and the retention of introns. Besides alternative spilcing, the mRNAs differ by truncation on the 3’ end. Variant 1 is one of ten mRNAs that has been shown to code for a protein, while the rest seem bound for nonsense mediated mRNA decay. AceView representation of C11orf73 isoforms File:Isoforms of C11orf73.jpg ## Promoter The Promoter region, GXP 47146, was found using the ElDorado tool from Genomatix. The 840 bp sequence is located before the HIKESHI gene at DNA points 86012753 to 86013592. The promoter is conserved in 12 of 12 orthologs and codes for 6 relevant transcripts. Conserved transcription factor binding sites from Genomatix ElDorado tool: ## Termination Termination of the mRNA product is encoded for within the cDNA of the gene. The end termination of an mRNA product generally has three main features: the poly A signal, the poly A tail, and an area of sequence that can form a stem loop structure. The poly A signal is a highly conserved site, six nucleotide long sequence. In eukaryotes the sequence is AATAAA and is located about 10-30 nucleotides from the poly A site. The AATAAA sequence is a highly conserved, eukaryotic polyA signal that signals for polyadenylation of the mRNA product 10-30 base pairs after the signal sequence. The polyA site for C11orf73 is GTA. # Gene expression HIKESHI was determined to be expressed ubiquitously at a high level of 2.3 times above the average. C11orf73 is expressed in a large number of human tissues. Between the Expression Profiles and the EST Profile on UniGene, only 11 tissues were shown not to express C11orf73, most likely due to small sample sizes in the tissue. # Protein The human HIKESHI gene encodes for a protein called uncharacterized protein C11orf73. The homologous mouse L7rn6 gene encodes a protein called lethal gene on chromosome 7 Rinchik 6. The encoded human protein is 197 amino acids long and weighs 21,628 Daltons. Through analogy to the mouse protein, the hypothetical function of the human HIKESHI protein is the organization and function of the secretory apparatus in lung cells. The protein domain known as DUF775 (Domain of Unknown Function 775) is located within both the human HIKESHI and mouse L7rn6 proteins. The DUF775 domain is 197 amino acids long, the same length as the protein. Other proteins that make up the DUF 775 super family by definition include all the orthologs of C11orf73. Hydropathy analysis shows that there are no extensive hydrophobic regions in the protein and, hence, it is concluded that HIKESHI is a cytoplasmic protein. The isoelectric point for C11orf73 is 5.108 suggesting it functions optimally in a more acidic environment. ## SNP The only SNP, or single-nucleotide polymorphism, for the C11orf73 sequence results in an amino acid change within the protein. The lack of other SNPs are most likely due to the high level of conservation of HIKESHI and the lethal effect a mutation in the protein bestows upon the organism. The phenotype for the SNP is unknown. ## Gene Neighborhood The surrounding genes of HIKESHI are CCDC81, ME3, and EED. The genetic neighborhood is looked at in order to get a better understanding of the possible function of the gene by looking at the function of the surrounding genes. The CCDC81 gene codes for an uncharacterized protein product and is oriented on the plus strand. CCDC81stands for coiled-coil domain containing 81 isoform 1. The ME3 gene stands for mitochondrial malic enzyme 3 precursor. Malic enzyme catalyzes the oxidative decarboxylation of malate to pyruvate using either NAD+ or NADP+ as a cofactor. Mammalian tissues contain 3 distinct isoforms of malic enzyme: a cytosolic NADP(+)-dependent isoform, a mitochondrial NADP(+)-dependent isoform, and a mitochondrial NAD(+)-dependent isoform. This gene encodes a mitochondrial NADP(+)-dependent isoform. Multiple alternatively spliced transcript variants have been found for this gene, but the biological validity of some variants has not been determined. The EED gene stands for embryonic ectoderm development isoform b and is a member of the Polycomb-group (PcG) family. PcG family members form multimeric protein complexes, which are involved in maintaining the transcriptional repressive state of genes over successive cell generations. This protein interacts with enhancer of zeste 2, the cytoplasmic tail of integrin beta7, immunodeficiency virus type 1 (HIV-1) MA protein, and histone deacetylase proteins. This protein mediates repression of gene activity through histone deacetylation, and may act as a specific regulator of integrin function. Two transcript variants encoding distinct isoforms have been identified for this gene. ## Interactions The programs STRING and Sigma-Aldrich’s Favorite Gene suggested possible protein interactions with C11orf73. ARGUL1, CRHBP, and EED were derived from textmining and HNF4A came from Sigma-Aldrich. ARGUL1 is an unknown protein with an unknown function. CRHBP is a corticotrophin releasing hormone binding protein which could possibly play a role in a signal cascade that involves or activates HIKESHI. EED, a neighboring protein of C11orf73, is an embryonic ectoderm development protein and is a member of the Polycomb-group (PcG) family. PcG family members form multimeric protein complexes, which are involved in maintaining the transcriptional repressive state of genes over successive cell generations. HNF4A is a transcription regulator and it is unknown if HNF4A regulates C11orf73's expression or simply interacts with it.[12 # Evolutionary History The evolutionary history of organisms can be determined using the sequences of orthologs as time references to create a phylogenetic tree. The CLUSTALW compares multiple sequences, the program can also be used to create such a phylogenetic tree based on the orthologs of C11orf73. The tree to the right shows the generated phylogenetic tree with a time line based on time of divergence. The tree made from the HIKESHI orthologs is identical to the literature phylogenetic tree, even grouping together similar organisms such as fish, birds, and fungi. ## Orthologs Homologous sequences are orthologous if they were separated by a speciation event: when a species diverges into two separate species, the divergent copies of a single gene in the resulting species are said to be orthologous. Orthologs, or orthologous genes, are genes in different species that are similar to each other because they originated from a common ancestor. Orthologous sequences provide useful information in taxonomic classification and phylogenetic studies of organisms. The pattern of genetic divergence can be used to trace the relatedness of organisms. Two organisms that are very closely related are likely to display very similar DNA sequences between two orthologs. Conversely, an organism that is further removed evolutionarily from another organism is likely to display a greater divergence in the sequence of the orthologs being studied. Table of Chromosome 11 open reading frame 73 Orthologs The table shows the 13 sequences (12 orthologs, 1 original sequence) along with protein name, accession numbers, nucleotide identity, protein identity, and E-values. The accession numbers are the identification numbers from the NCBI Protein database. The nucleotide sequence can be accessed from the protein’s sequence page from DBSOURCE, which gives the accession number and is a link to the nucleotide’s sequence page. The length of both the nucleotide and protein sequence for each ortholog and its respective organism are listed in the table as well. Next to the sequence lengths are the identities of the ortholog to the original HIKESHI gene. The identities and E-values were acquired using the global alignment program, ALIGN, from the SDSC Biology Workbench and BLAST from NCBI. The graph shows the percent identity of the ortholog against the divergence time of the organism to produce a mostly linear curve. The two main joints within the curve suggest times of gene duplication, around 450 million years and 1150 million years ago respectively. The paralogs from the gene duplications are probably so dissimilar from the highly conserved orthologs of HIKESHI that it was not found using the Blink or BLAST tools. The value m (total number of amino acid changes that have occurred in a 100 amino acid segment), which is the corrected value of n (number of amino acid differences from the template sequence), is also used to calculate λ (the average amino acid changes per year, usually represented in values of λE9).	HIKESHI HIKESHI is a protein important in lung and multicellular organismal development[1] that, in humans, is encoded by the HIKESHI gene.[2] HIKESHI is found on chromosome 11 in humans and chromosome 7 in mice. Similar sequences (orthologs) are found in most animal and fungal species. The mouse homolog, lethal gene on chromosome 7 Rinchik 6 protein is encoded by the l7Rn6 gene.[3] When the l7Rn6 protein is disrupted in mice, the mice display severe emphysema at birth as a result of disorganization of the Golgi apparatus and formation of aberrant vesicular structures within club cells.[1][needs update] # Gene HIKESHI is a protein-coding gene in Homo sapiens. Alternate names for the gene are FLJ43020, HSPC138, HSPC179, and L7RN6. Located on long arm of chromosome 11 at area q14.2, the entire gene including introns and exons is 42,698 base pairs on the plus strand. The mRNA of HIKESHI Variant 1 includes exons 1, 3, 4, 5, and 7 amounting to 1,183 base pairs, with base pairs 239 to 832 representing the coding regions. ## Alternative Splicing Variant 1 is the longest and most common protein coding variant. The three other main variants use an alternate exon sequence that throws off the reading frame, causing early termination of the mRNA sequence and undergoes protein decay. The table below shows the different variants and exon usage. The four variants shown in the table above are the most common isoforms found in human cells. There are a total of 13 alternatively spliced sequences and 3 unspliced forms that utilize two alternative promoters. The mRNA variants differ on the combination of 8 different exons, alternate, overlapping exons, and the retention of introns. Besides alternative spilcing, the mRNAs differ by truncation on the 3’ end. Variant 1 is one of ten mRNAs that has been shown to code for a protein, while the rest seem bound for nonsense mediated mRNA decay. AceView[4] representation of C11orf73 isoforms File:Isoforms of C11orf73.jpg ## Promoter The Promoter region, GXP 47146, was found using the ElDorado[5] tool from Genomatix. The 840 bp sequence is located before the HIKESHI gene at DNA points 86012753 to 86013592. The promoter is conserved in 12 of 12 orthologs and codes for 6 relevant transcripts. Conserved transcription factor binding sites from Genomatix ElDorado tool: ## Termination Termination of the mRNA product is encoded for within the cDNA of the gene. The end termination of an mRNA product generally has three main features: the poly A signal, the poly A tail, and an area of sequence that can form a stem loop structure. The poly A signal is a highly conserved site, six nucleotide long sequence. In eukaryotes the sequence is AATAAA and is located about 10-30 nucleotides from the poly A site. The AATAAA sequence is a highly conserved, eukaryotic polyA signal that signals for polyadenylation of the mRNA product 10-30 base pairs after the signal sequence. The polyA site for C11orf73 is GTA. # Gene expression HIKESHI was determined to be expressed ubiquitously at a high level of 2.3 times above the average. C11orf73 is expressed in a large number of human tissues.[6][7] Between the Expression Profiles and the EST Profile on UniGene, only 11 tissues were shown not to express C11orf73, most likely due to small sample sizes in the tissue. # Protein The human HIKESHI gene encodes for a protein called uncharacterized protein C11orf73.[2] The homologous mouse L7rn6 gene encodes a protein called lethal gene on chromosome 7 Rinchik 6.[3] The encoded human protein is 197 amino acids long and weighs 21,628 Daltons. Through analogy to the mouse protein, the hypothetical function of the human HIKESHI protein is the organization and function of the secretory apparatus in lung cells.[1] The protein domain known as DUF775 (Domain of Unknown Function 775) is located within both the human HIKESHI and mouse L7rn6 proteins. The DUF775 domain is 197 amino acids long, the same length as the protein. Other proteins that make up the DUF 775 super family by definition include all the orthologs of C11orf73. Hydropathy analysis shows that there are no extensive hydrophobic regions in the protein and, hence, it is concluded that HIKESHI is a cytoplasmic protein. The isoelectric point for C11orf73 is 5.108 suggesting it functions optimally in a more acidic environment. [8] ## SNP The only SNP,[9] or single-nucleotide polymorphism, for the C11orf73 sequence results in an amino acid change within the protein. The lack of other SNPs are most likely due to the high level of conservation of HIKESHI and the lethal effect a mutation in the protein bestows upon the organism. The phenotype for the SNP is unknown. ## Gene Neighborhood The surrounding genes of HIKESHI are CCDC81, ME3, and EED. The genetic neighborhood is looked at in order to get a better understanding of the possible function of the gene by looking at the function of the surrounding genes. [10] The CCDC81 gene codes for an uncharacterized protein product and is oriented on the plus strand. CCDC81stands for coiled-coil domain containing 81 isoform 1. The ME3 gene stands for mitochondrial malic enzyme 3 precursor. Malic enzyme catalyzes the oxidative decarboxylation of malate to pyruvate using either NAD+ or NADP+ as a cofactor. Mammalian tissues contain 3 distinct isoforms of malic enzyme: a cytosolic NADP(+)-dependent isoform, a mitochondrial NADP(+)-dependent isoform, and a mitochondrial NAD(+)-dependent isoform. This gene encodes a mitochondrial NADP(+)-dependent isoform. Multiple alternatively spliced transcript variants have been found for this gene, but the biological validity of some variants has not been determined.[11] The EED gene stands for embryonic ectoderm development isoform b and is a member of the Polycomb-group (PcG) family. PcG family members form multimeric protein complexes, which are involved in maintaining the transcriptional repressive state of genes over successive cell generations. This protein interacts with enhancer of zeste 2, the cytoplasmic tail of integrin beta7, immunodeficiency virus type 1 (HIV-1) MA protein, and histone deacetylase proteins. This protein mediates repression of gene activity through histone deacetylation, and may act as a specific regulator of integrin function. Two transcript variants encoding distinct isoforms have been identified for this gene.[12] ## Interactions The programs STRING[13] and Sigma-Aldrich’s Favorite Gene[14] suggested possible protein interactions with C11orf73. ARGUL1, CRHBP, and EED were derived from textmining and HNF4A came from Sigma-Aldrich. ARGUL1 is an unknown protein with an unknown function. CRHBP is a corticotrophin releasing hormone binding protein which could possibly play a role in a signal cascade that involves or activates HIKESHI. EED, a neighboring protein of C11orf73, is an embryonic ectoderm development protein and is a member of the Polycomb-group (PcG) family. PcG family members form multimeric protein complexes, which are involved in maintaining the transcriptional repressive state of genes over successive cell generations. HNF4A is a transcription regulator and it is unknown if HNF4A regulates C11orf73's expression or simply interacts with it.[12 # Evolutionary History The evolutionary history of organisms can be determined using the sequences of orthologs as time references to create a phylogenetic tree. The CLUSTALW[15] compares multiple sequences, the program can also be used to create such a phylogenetic tree based on the orthologs of C11orf73. The tree to the right shows the generated phylogenetic tree with a time line based on time of divergence. The tree made from the HIKESHI orthologs is identical to the literature phylogenetic tree, even grouping together similar organisms such as fish, birds, and fungi. ## Orthologs Homologous sequences are orthologous if they were separated by a speciation event: when a species diverges into two separate species, the divergent copies of a single gene in the resulting species are said to be orthologous. Orthologs, or orthologous genes, are genes in different species that are similar to each other because they originated from a common ancestor. Orthologous sequences provide useful information in taxonomic classification and phylogenetic studies of organisms. The pattern of genetic divergence can be used to trace the relatedness of organisms. Two organisms that are very closely related are likely to display very similar DNA sequences between two orthologs. Conversely, an organism that is further removed evolutionarily from another organism is likely to display a greater divergence in the sequence of the orthologs being studied. Table of Chromosome 11 open reading frame 73 Orthologs The table shows the 13 sequences (12 orthologs, 1 original sequence) along with protein name, accession numbers, nucleotide identity, protein identity, and E-values. The accession numbers are the identification numbers from the NCBI Protein database. The nucleotide sequence can be accessed from the protein’s sequence page from DBSOURCE, which gives the accession number and is a link to the nucleotide’s sequence page. The length of both the nucleotide and protein sequence for each ortholog and its respective organism are listed in the table as well. Next to the sequence lengths are the identities of the ortholog to the original HIKESHI gene. The identities and E-values were acquired using the global alignment program, ALIGN, from the SDSC Biology Workbench and BLAST from NCBI. The graph shows the percent identity of the ortholog against the divergence time of the organism to produce a mostly linear curve. The two main joints within the curve suggest times of gene duplication, around 450 million years and 1150 million years ago respectively. The paralogs from the gene duplications are probably so dissimilar from the highly conserved orthologs of HIKESHI that it was not found using the Blink or BLAST tools. The value m (total number of amino acid changes that have occurred in a 100 amino acid segment), which is the corrected value of n (number of amino acid differences from the template sequence), is also used to calculate λ (the average amino acid changes per year, usually represented in values of λE9).	https://www.wikidoc.org/index.php/HIKESHI
3c0ff741f4024c9bb1ee54160da98be22f0fe89c	wikidoc	HLA-A11	HLA-A11 HLA-A11 (A11) is an HLA-A serotype. The serotype identifies the more common HLA-A11 gene products. A11 is more common in eastern Asia particularly along the coastal regions of china. # Serotype Serotyping of A11 demostrates better recognition of the 1101 gene products and poorer recognition of other A11 gene products. Ther are ~40 recognized alleles of A11. There is only one null classified as A11. # Disease Associations ### By allele A*1104 is associated with increased risk for cervical neoplasia resulting from human papillomavirus infection # A11-B Haplotypes A11-B13 - A11-Cw2-B13 (Li) - A11-Cw9-B13 (Southern China & SE Asia) - A11-C10-B13 Buyi - A11-CBL-B13 Northern China	HLA-A11 HLA-A11 (A11) is an HLA-A serotype. The serotype identifies the more common HLA-A11 gene products. A11 is more common in eastern Asia particularly along the coastal regions of china. # Serotype Serotyping of A11 demostrates better recognition of the 1101 gene products and poorer recognition of other A11 gene products. Ther are ~40 recognized alleles of A11. There is only one null classified as A11. # Disease Associations ### By allele A*1104 is associated with increased risk for cervical neoplasia resulting from human papillomavirus infection[2] # A11-B Haplotypes A11-B13 - A11-Cw2-B13 (Li) - A11-Cw9-B13 (Southern China & SE Asia) - A11-C10-B13 Buyi - A11-CBL-B13 Northern China	https://www.wikidoc.org/index.php/HLA-A11
4672f41f638fd547550bd8794f3380144e82bc57	wikidoc	HLA-A24	HLA-A24 HLA-A24 (A24) is an HLA-A serotype. The serotype identifies the more common HLA-A24 gene products. A24 is a split antigen that is also recognized by the A9 broad antigen type. This broad antigen also recognizes the similar A23 types. A24 is common in Austronesia. A2402 has one of the highest A allele frequencies for a number of peoples, including Papua New Guineans, Indigeonous Taiwanese (Eastern Tribals), Yupik and Greenland Eskimos. It is common over much of Southeastern Asia. In eurasia it is least common in Ireland, and it is relatively uncommon in Africa except North Africa and Kenya. # Serotype There are over 90 known A24 alleles, 69 code for different isoforms and 7 are nulls. # Disease Associations ### By serotype A24 has a secondary risk factor for myasthenia gravis,, Buerger's disease ### By allele A2402 is a secondary risk factor, alters type 1 diabetes risk, and allele associated with thyomoma induced myasthenia gravis. # A24-B Haplotypes A24-Cw7-B39 A24-Cw10-B60 A24-Cw10-B61 A24-B48 ### A24-Cw4-B35 This particular haplotype is common across a fairly wide region, possibly the most widely spread A-Cw-B haplotype in humans. Cw4-B35 has a node within the region once referred to as Thracia/Dacia. ### A24-Cw*14-B51	HLA-A24 HLA-A24 (A24) is an HLA-A serotype. The serotype identifies the more common HLA-A24 gene products. A24 is a split antigen that is also recognized by the A9 broad antigen type. This broad antigen also recognizes the similar A23 types. A24 is common in Austronesia. A2402 has one of the highest A allele frequencies for a number of peoples, including Papua New Guineans, Indigeonous Taiwanese (Eastern Tribals), Yupik and Greenland Eskimos. It is common over much of Southeastern Asia. In eurasia it is least common in Ireland, and it is relatively uncommon in Africa except North Africa and Kenya. # Serotype There are over 90 known A24 alleles, 69 code for different isoforms and 7 are nulls. # Disease Associations ### By serotype A24 has a secondary risk factor for myasthenia gravis,,[2] Buerger's disease[3] ### By allele A2402 is a secondary risk factor,[4] alters type 1 diabetes risk,[5][6] and allele associated with thyomoma induced myasthenia gravis. # A24-B Haplotypes A24-Cw7-B39 A24-Cw10-B60 A24-Cw10-B61 A24-B48 ### A24-Cw4-B35 This particular haplotype is common across a fairly wide region, possibly the most widely spread A-Cw-B haplotype in humans. Cw4-B35 has a node within the region once referred to as Thracia/Dacia. ### A24-Cw*14-B51	https://www.wikidoc.org/index.php/HLA-A24
242bb749c6bb7780f23d715e5a90ff8f42887958	wikidoc	HLA-A25	HLA-A25 HLA-A25 (A25) is an HLA-A serotype. The serotype identifies the more common HLA-A25 gene products. A25 is a split antigen of the A10 broad antigen serotype group. It is believed to have been formed by a single gene conversion between another HLA-A and the A2601 allele. A26 is more common in Western Europe. # Serotype There are 7 alleles for A25, 6 that result in different isoforms. ## A25 frequencies A2501 distribution is primarily located in western Eurasia. Frequency tends to be highest in the populations that underwent later neolithization suggesting A2501 spread in Europe. The high frequency in Saudi Arabia is suggestive of a source.	HLA-A25 HLA-A25 (A25) is an HLA-A serotype. The serotype identifies the more common HLA-A25 gene products. A25 is a split antigen of the A10 broad antigen serotype group. It is believed to have been formed by a single gene conversion between another HLA-A and the A2601 allele.[1] A26 is more common in Western Europe. # Serotype There are 7 alleles for A25, 6 that result in different isoforms. ## A25 frequencies A2501 distribution is primarily located in western Eurasia. Frequency tends to be highest in the populations that underwent later neolithization suggesting A2501 spread in Europe. The high frequency in Saudi Arabia is suggestive of a source.	https://www.wikidoc.org/index.php/HLA-A25
3243270492a83d723cc47a9b6350663f7df9078c	wikidoc	HLA-A31	HLA-A31 HLA-A31 (A31) is an HLA-A serotype. The serotype identifies the more common HLA-A31 gene products. A31 is a split antigen of the A19 broad antigen serotype group. It is similar to the antigens A29, 30, A32,A33, and A74. A31 is more common in Japan, Siberia and Indigenous Americans. It is also more frequent in NE Europe than SW Europe. # Serotype There is substantive cross reaction of A30 with A3101, otherwise serological identification is good. # A31 alleles ### A310102 # A31-B Haplotypes Examination of A31 haplotypes reveal a probably connection across northern Eurasia during the prehistoric period. Frequencies of the more 'tale-tell' haplotypes (A31-B60, B61, and B62) fall from NE to SW Europe. Other haplotypes appears to have spread from the middle east (A31-B51 and A31-B35).	HLA-A31 HLA-A31 (A31) is an HLA-A serotype. The serotype identifies the more common HLA-A31 gene products. A31 is a split antigen of the A19 broad antigen serotype group. It is similar to the antigens A29, 30, A32,A33, and A74. A31 is more common in Japan, Siberia and Indigenous Americans. It is also more frequent in NE Europe than SW Europe. # Serotype There is substantive cross reaction of A30 with A3101, otherwise serological identification is good. # A31 alleles ### A310102 # A31-B Haplotypes Examination of A31 haplotypes reveal a probably connection across northern Eurasia during the prehistoric period. Frequencies of the more 'tale-tell' haplotypes (A31-B60, B61, and B62) fall from NE to SW Europe. Other haplotypes appears to have spread from the middle east (A31-B51 and A31-B35).	https://www.wikidoc.org/index.php/HLA-A31
8cfb4fc3598483be88bdeead409c20bb0efeb958	wikidoc	HLA-A32	HLA-A32 HLA-A32 (A32) is an HLA-A serotype. The serotype identifies the more common HLA-A32 gene products. A32 is a split antigen of the A19 serotype group. This group also includes A29, A30, A31, A33, and A74 serotypes # Serotype Serotyping efficiency for the predominant allele is good. There are 16 known alleles that result in 15 isoforms of HLA-A32. One isoform may be poorly expressed. ## HLA-A3201 allele frequencies A32 is most common around the Persion Gulf and the Mediterranean Basin. It has a consistent presence in Europe. The A32 frequenceies in the more isolated (genetically) peoples of Europe suggests that the A32 rise in the mediterranean may only be partially attributable to recent migrations from the middle eastern region. There is a node in southern europe around the Ionian Sea in which specific, European, A32-haplotypes are elevated. ## A32 Haplotypes A common A32 haplotype A3201-B5101 can be found in Oman, United Arab Emirates, SE Iran, Bulgaria, and Portugal. A second, A3201-B3501 can be in the Omani, UAE, and Portugal.	HLA-A32 HLA-A32 (A32) is an HLA-A serotype. The serotype identifies the more common HLA-A32 gene products. A32 is a split antigen of the A19 serotype group. This group also includes A29, A30, A31, A33, and A74 serotypes # Serotype Serotyping efficiency for the predominant allele is good. There are 16 known alleles that result in 15 isoforms of HLA-A32. One isoform may be poorly expressed.[2] ## HLA-A3201 allele frequencies A32 is most common around the Persion Gulf and the Mediterranean Basin. It has a consistent presence in Europe. The A32 frequenceies in the more isolated (genetically) peoples of Europe suggests that the A32 rise in the mediterranean may only be partially attributable to recent migrations from the middle eastern region. There is a node in southern europe around the Ionian Sea in which specific, European, A32-haplotypes are elevated. ## A32 Haplotypes A common A32 haplotype A3201-B5101 can be found in Oman, United Arab Emirates, SE Iran, Bulgaria, and Portugal. A second, A3201-B3501 can be in the Omani, UAE, and Portugal.	https://www.wikidoc.org/index.php/HLA-A32
5c85242629ccadca079032c2a80d20aa219130af	wikidoc	HLA-A33	HLA-A33 HLA-A33 (A33) is an HLA-A serotype. The serotype identifies the HLA-A3301 gene product. A33 is a split antigen type of the A19 broad antigen type. A33 is common in India and certain parts of Africa. # Serotype # A33 frequencies 'A33 shows two different distributions that can be discriminated by subtyping capability of SSP-PCR. ### A3301 distribution The first distribution appears to have a Western distribution that introgresses into Europe as a result of the Post-neolithic periods. It is commonly found in linkage disequilibration within the A3301-Cw0802-B1402 haplotype which can be extended to DRB1 and DQB1 in certain instances(See Below). The source of its general expansion appears to be the middle east or the levant, as it is found in the Palestinian population. B14 splits into B64 (B1401) and B65 (B1402) but the only arabian people which show both antigens are the United Arab Emirates. ### A3303 distribution Certain alleles confound population histories. At the top of that list is A3303. This allele appears to jump, literally, out of West Africa into South Asia. The point of origin is africa, most likely central or western Africa given the low levels in East Africa (although much of East Africa is undersampled). In certain tested populations of the Middle East the leve of A3303 is either very low, or non-existent. Within East Africa Sudan appears to be the highest at around 2%. The frequency of A3303 begins to rise in eastern Arabia (Oman, UAE) and then markedly rise in the Brahui and Balochi of Pakistan. One haplotype stands out, the A33-B58-DR3-DQ2 haplotype which is found in West Africa, in Sudan, and Pakistan, scattered along West Indias coast, the Turkic republics and appears to have recently introgressed into Korea (post-Yayoi period of Japan) and China. So recent arrival into asia that the level of HLA DR3-DQ2 in korea of 2.9%. Korea is the major recent source of Japanese genes, by the Yayoi period that lasted from 3000 to 1600 years ago approximately 3/4ths of Japanese genetic makeup is attributed to this migration. And yet there is trace DR3-DQ2 in Japanese, none in the Ainu nor many other indigeonous Siberian groups. # A33 Haplotypes ### A33-Cw8-B14-DR1-DQ5 When dealing with haplotypes, if one assumes that linkage disequilibrium is random, then one can estimate the time of equilibration based on the size of the haplotype, the A-B-DR haplotype is over 2 million nucleotides in length. Given this length it is unlikely it spread during the Neolithic period. A more like guess as to when it spread was the early historic period, with the spread of the Phonecian and Mycenaean culture throughout the mediterranean. Its presence in India, particularly northern India, indicates possible spread of this haplotype within the black sea region prior to the migration of Indo-aryan culture across the Indus River. The specific nomenclature for this type is: A3301 : C0802 : B1402 : DRB10102 : DQA10102 : DQB10501 ### A33-B44 This haplotype appears to precede A33-B58 in Asia, bringing with it the DR7-DQ2 haplotype. There are two versions of the haplotype, possibly of different origins, its a good reason why serotyping alone should not be relied upon. The first haplotype is A33-Cw14-B44-DR13-DQ6.4 A3303 : C1403 : B4403 : DRB11302 : DQA10102 : DQB10604 : DPB10401 This haplotype is found in Japan and Korea, and it is the most common 5 locus HLA type in Korea, high at 4.2%, 25 times higher than in China. In Japan it is 4.8% and can be extended to DPB1 at 3.6%. While clearly not showing the level of disequilibrium of the Super B8 haplotype, the level of disequilibrium is high, indicating an expansive migration into these regions at some time in the recent past, most likely in the period precedeing the Yayoi period of Japan. A3303 : C0701 : B4403 : DRB10701 : DQA10201? : DQB10202 The second haplotype, like A33-B58 is found in Korea but not in Japan. This haplotype carries the other common DQ2 haplotype, DQ2.2. The Cw0701 is found in the A33-B58 haplotype and is like the result of a recombination betwee A33-Cw7 and a different B44-DR7 haplotype. These haplotypes indicate that interpreting population relationships by allele or even by low resolution haplotype information is error-prone and suggests the need for high resolution multigene haplotype studies. ### A33-Cw3-B58-DR3-DQ2 Within eastern Asia A3303 is in linkage disiquilbrium with on haplotype in particular, the specific genetic makeup is: A3303 : C0302 : B5801 : DRB10301 : DQA10501 : DQB10201 It is interesting that the Cw allele in the pakistani population is the same as the allele in the east asian population C0302. 8.3 of 11.1% of the A33-B58 in the Baloch Pakistani can is linked to DR3 and presumbably DQ2.5 (There are few exceptions outside of Africa). This extends a haplotype the forms a semi-circle around the Indian subcontinent indicating a subsantive and relatively recent genetic relationship. The parsis of Pakistan lack A33-B58, as with groups to the far west of pakistan. The A33-B58-DR3-DQ2 haplotype appears to have originated in whole from West Africa, with current possibilities for Sudan or Northern Ethiopia as points of exit from africa and a migration by the Indian ocean to the western side of the Indus River. ### A33-Cw7-B58-DR13-DQ6 Within eastern Asia A3303 is in linkage disiquilbrium with on haplotype in particular, the specific genetic makeup is: A3303 : C0701 : B5801 : DRB11302 : DQA10102 : DQB10609 This haplotype is composed of genes most frequent in parts of western Africa. This includes the A3303, B5801, DRB11302, and DQB10609. The DRB10609 haplotype in nodal in east/central africa in the Ugandan, Rwanda, Congo, Cameroon whereas the allele is at low frequencies in Western Europe, and its distribution is also consistent with a migration from east africa direct to the Lower Indus River.	HLA-A33 HLA-A33 (A33) is an HLA-A serotype. The serotype identifies the HLA-A3301 gene product. A33 is a split antigen type of the A19 broad antigen type. A33 is common in India and certain parts of Africa.[1] # Serotype # A33 frequencies 'A33 shows two different distributions that can be discriminated by subtyping capability of SSP-PCR. ### A3301 distribution The first distribution appears to have a Western distribution that introgresses into Europe as a result of the Post-neolithic periods. It is commonly found in linkage disequilibration within the A3301-Cw0802-B1402 haplotype which can be extended to DRB1 and DQB1 in certain instances(See Below). The source of its general expansion appears to be the middle east or the levant, as it is found in the Palestinian population. B14 splits into B64 (B1401) and B65 (B1402) but the only arabian people which show both antigens are the United Arab Emirates. ### A3303 distribution Certain alleles confound population histories. At the top of that list is A3303. This allele appears to jump, literally, out of West Africa into South Asia. The point of origin is africa, most likely central or western Africa given the low levels in East Africa (although much of East Africa is undersampled). In certain tested populations of the Middle East the leve of A3303 is either very low, or non-existent. Within East Africa Sudan appears to be the highest at around 2%. The frequency of A3303 begins to rise in eastern Arabia (Oman, UAE) and then markedly rise in the Brahui and Balochi of Pakistan. One haplotype stands out, the A33-B58-DR3-DQ2 haplotype which is found in West Africa, in Sudan, and Pakistan, scattered along West Indias coast, the Turkic republics and appears to have recently introgressed into Korea (post-Yayoi period of Japan) and China. So recent arrival into asia that the level of HLA DR3-DQ2 in korea of 2.9%. Korea is the major recent source of Japanese genes, by the Yayoi period that lasted from 3000 to 1600 years ago approximately 3/4ths of Japanese genetic makeup is attributed to this migration. And yet there is trace DR3-DQ2 in Japanese, none in the Ainu nor many other indigeonous Siberian groups. # A33 Haplotypes ### A33-Cw8-B14-DR1-DQ5 When dealing with haplotypes, if one assumes that linkage disequilibrium is random, then one can estimate the time of equilibration based on the size of the haplotype, the A-B-DR haplotype is over 2 million nucleotides in length. Given this length it is unlikely it spread during the Neolithic period. A more like guess as to when it spread was the early historic period, with the spread of the Phonecian and Mycenaean culture throughout the mediterranean. Its presence in India, particularly northern India, indicates possible spread of this haplotype within the black sea region prior to the migration of Indo-aryan culture across the Indus River. The specific nomenclature for this type is: A3301 : C0802 : B1402 : DRB10102 : DQA10102 : DQB10501 ### A33-B44 This haplotype appears to precede A33-B58 in Asia, bringing with it the DR7-DQ2 haplotype. There are two versions of the haplotype, possibly of different origins, its a good reason why serotyping alone should not be relied upon. The first haplotype is A33-Cw14-B44-DR13-DQ6.4[35] A3303 : C1403 : B4403 : DRB11302 : DQA10102 : DQB10604 : DPB10401 This haplotype is found in Japan and Korea, and it is the most common 5 locus HLA type in Korea, high at 4.2%, 25 times higher than in China. In Japan it is 4.8% and can be extended to DPB1 at 3.6%. While clearly not showing the level of disequilibrium of the Super B8 haplotype, the level of disequilibrium is high, indicating an expansive migration into these regions at some time in the recent past, most likely in the period precedeing the Yayoi period of Japan. A3303 : C0701 : B4403 : DRB10701 : DQA10201? : DQB10202 The second haplotype, like A33-B58 is found in Korea but not in Japan.[21] This haplotype carries the other common DQ2 haplotype, DQ2.2. The Cw0701 is found in the A33-B58 haplotype and is like the result of a recombination betwee A33-Cw7 and a different B44-DR7 haplotype. These haplotypes indicate that interpreting population relationships by allele or even by low resolution haplotype information is error-prone and suggests the need for high resolution multigene haplotype studies. ### A33-Cw3-B58-DR3-DQ2 Within eastern Asia A3303 is in linkage disiquilbrium with on haplotype in particular, the specific genetic makeup is: A3303 : C0302 : B5801 : DRB10301 : DQA10501 : DQB10201 It is interesting that the Cw allele in the pakistani population is the same as the allele in the east asian population C0302. 8.3 of 11.1% of the A33-B58 in the Baloch Pakistani can is linked to DR3 and presumbably DQ2.5 (There are few exceptions outside of Africa). This extends a haplotype the forms a semi-circle around the Indian subcontinent indicating a subsantive and relatively recent genetic relationship. The parsis of Pakistan lack A33-B58, as with groups to the far west of pakistan. The A33-B58-DR3-DQ2 haplotype appears to have originated in whole from West Africa, with current possibilities for Sudan or Northern Ethiopia as points of exit from africa and a migration by the Indian ocean to the western side of the Indus River. ### A33-Cw7-B58-DR13-DQ6 Within eastern Asia A3303 is in linkage disiquilbrium with on haplotype in particular, the specific genetic makeup is: A3303 : C0701 : B5801 : DRB11302 : DQA10102 : DQB10609 This haplotype is composed of genes most frequent in parts of western Africa. This includes the A3303, B5801, DRB11302, and DQB10609. The DRB10609 haplotype in nodal in east/central africa in the Ugandan, Rwanda, Congo, Cameroon whereas the allele is at low frequencies in Western Europe, and its distribution is also consistent with a migration from east africa direct to the Lower Indus River.	https://www.wikidoc.org/index.php/HLA-A33
e1be3f27c601c8458148c0e4cf6af262fb37859b	wikidoc	HLA-A34	HLA-A34 HLA-A34 (A34) is an HLA-A serotype. A34 is a split antigen of the A10 broad antigen serotype. This serotype has related antigens A25 and A26 but A34 is most similar to A66. # Serotype # A34 allele frequencies ### A3401 A3401 when found outside of africa is primarily found in the South Asia, Austronesia and the South/Central part of the West Pacific Rim (WPR). It appears to have made it to Eastern Taiwan's indigenous tribes (Ami, Yami) but not more north of this region. It has not been detected in any sampling of Japan. Over most of the East Pacific Rim region were it is found it is limited to 1 or 2 common haplotypes in strong linkage disequilibrium. This indicates its presence in the WPR region is the result of recent migrations. The A3401 migration from Africa is supported by its presence in East Africa and South Africa and by current models of human migration, this allele was likely represented in the first wave of immigrants. However in areas were mixtures of these alleles are commonly found, Persian Gulf region and India, A3401 is relatively uncommon, scarce, or absent. The exception is Saudi Arabia, in which A34 is at 2.8% and amoung Israeli Jews at 8.8%. Some reports that both A3401 and A3402 are in the region, but questionable whether these are perpetually maintained allele frequencies are simply recent migrants. ### A3402 A3402 is more frequently found in the west, it is found in Iberia and along the mediterranean, but its frequency is low, the exception may be in the Levant, but it is unclear whether this is A3401 or A3402. # A34-B Haplotypes A34 is in strong linkage disequilibrium in many areas of the world, but particularly SE Asia and Oceania. The most prominent of these haplotypes is A34-Cw11(1)-B56. This haplotype is found from Western Australia to Taiwan to New Zealand indicating a recent genetic linkage between these peoples. Another frequently found haplotype is the A34-B61 (A3401:Cw04:B*B4002) haplotype. This haplotype has a similar distribution as A34-B56. These haplotypes indicate that long range/oversees migrations were taking place in Austronesias (late paleolithic) prehistory.	HLA-A34 HLA-A34 (A34) is an HLA-A serotype. A34 is a split antigen of the A10 broad antigen serotype. This serotype has related antigens A25 and A26[1] but A34 is most similar to A66. # Serotype # A34 allele frequencies ### A3401 A3401 when found outside of africa is primarily found in the South Asia, Austronesia and the South/Central part of the West Pacific Rim (WPR). It appears to have made it to Eastern Taiwan's indigenous tribes (Ami, Yami) but not more north of this region. It has not been detected in any sampling of Japan. Over most of the East Pacific Rim region were it is found it is limited to 1 or 2 common haplotypes in strong linkage disequilibrium. This indicates its presence in the WPR region is the result of recent migrations. The A3401 migration from Africa is supported by its presence in East Africa and South Africa and by current models of human migration, this allele was likely represented in the first wave of immigrants. However in areas were mixtures of these alleles are commonly found, Persian Gulf region and India, A3401 is relatively uncommon, scarce, or absent. The exception is Saudi Arabia, in which A34 is at 2.8% and amoung Israeli Jews at 8.8%. Some reports that both A3401 and A3402 are in the region, but questionable whether these are perpetually maintained allele frequencies are simply recent migrants. ### A3402 A3402 is more frequently found in the west, it is found in Iberia and along the mediterranean, but its frequency is low, the exception may be in the Levant, but it is unclear whether this is A3401 or A3402. # A34-B Haplotypes A34 is in strong linkage disequilibrium in many areas of the world, but particularly SE Asia and Oceania. The most prominent of these haplotypes is A34-Cw11(1)-B56. This haplotype is found from Western Australia to Taiwan to New Zealand indicating a recent genetic linkage between these peoples. Another frequently found haplotype is the A34-B61 (A3401:Cw04:B*B4002) haplotype. This haplotype has a similar distribution as A34-B56. These haplotypes indicate that long range/oversees migrations were taking place in Austronesias (late paleolithic) prehistory.	https://www.wikidoc.org/index.php/HLA-A34
4ca1f2c80b8a54c786f6ef7e9c8c0be40b688c55	wikidoc	HLA-A68	HLA-A68 HLA-A68 (A68) is an HLA-A serotype. The serotype is a split antigen serotype also recognized by the broad antigen serotype A28. The closely related A6901 is derived, by recombination from A68. # Serotype # Disease Associations ### By allele A68 is associated with higher viral load in HIV . A68 may be protective against symptomatic heart disease in Chaga's cardiomyopathy. # Allele freqeuncies A68 can be subdivided into 3 alleles, 6801, 6802, 6803. 6801 can also be subdivided into 680101 and 680102 (previously called 68011 and 68012). ### A6801 A6801 is higher in certain Native American groups, South Asian peoples, African peoples, however 6801 is at low levels in most of SE Asia, particularly the indigeonous populations. This is also reflected by low levels along the West Pacific Rim including Japan. The hiatus of 6801 breaks in Northern Japan with the 3% frequency found in the Ainu, which continues to increase with Arctic peoples and and falls of in Native Americans. Whereas in the Western Eurasia's northern regions, A6801 falls off. In both Africa and the New World both A680101 and A680102 can be found. Although in the New World A680102 is more prevalent. ### A6802 A6802 has a global node within certain native peoples of South America, at 37%. A secondary node can be found in Africa. Like 6801 there is an hiatus of 6802 in SE Asia's indigeonous populations, indicating that this population is not a likely source within the native peoples of the New World. Levels are generally low (<1%) in Europe except along the Mediterranean coast. In Africa, higher levels can be found in Kenya and in Western Africa and the Cape Verde Islands. A note on purity, the notion that A6802 is of indigeonous native American origin can be challenged based on possibility of introgression from Europeans and Africans. In the case of the Yucpa this is not teneble. The Yucpa have an HLA-DQ8 frequency of ~80%, the highest DQ allele frequency in the world, this tribe shows little evidence of European genetic introgression, in addition the closest DQ8 frequency in terms of Africa are the isolated !Kung of Namibia. There are two possible sources of A6802: Africa direct and Africa via Asia. The associated B alleles (B48, B61) point toward and Asian origin or an African source of very ancient origin, since time would be required to recombine Asian typical B alleles with A68. In the Spanish, A28 levels are 3.1% of this ~0.5% is A6901, A6802 is about 2.0% which means the net level of A6802 to A6805 in the Spanish is ~0.5%. Of 11 NA groups surveyed 9 are above and 2 are below 0.5%. Of the two Spanish groups 1 (Andalusia - 1.5%) is above and the other (Catalon 0.0%) is below. In an admixture model Spanish introgression does not explain A6802 in the New World. The Asian model of migration shows no single people NE of Pakistan that has A6802. ### A6803 A6803 can be found in native peoples of the New World and in Central Asia, in Africa it appears to be limited to West and Central Africans. This distribution along with the information on 6801 and 6802 suggests a probable redistribution of 68 alleles from Africa after the initial migration from East Africa that colonized Southeast Asia. It also provides support for 2 waves of migration from Asia to the New World or, at minimum, an unknown mixing area of West Pacific Rim haplotypes and West African/Middle Eastern derived haplotypes in Eastern Asia before the first migration. At present the incursion of Western Eurasian peoples into East Asia follows evidence for reuse of transbiakal region after 18,300 years and correlates with the insipient Jomon period of Japan several thousands of years later. Certain alleles and haplotypes of HLA in South Americans target Japans estimated pre-Yayoi composition, but other peoples, for example in western Mexico are most similar to the Ainu and the peoples of the Amur basin. ### A6805 A6805 is found in the Guatemalan and Central African Mbenzele at low levels. # A68 haplotypes The genetic distance between Native Americans and Eurasians is too great for the persistence of shared haplotypes, particularly in light of the lower levels in most of Siberia. The link of haplotypes with Western Africa may be significant, and may indicate a rapid eastward migration and admixing within the late paleolithic period. ### Indigeonous American haplotypes A680102-B35 haplotypes - A680102 Cw0304 B3506 (A68-Cw10-B35) - A68-Cw4-B35 (Terena, Seri (Mexico)) A680102 Cw0401 B83521 (A68-Cw4-B35) (Terena) - A680102 Cw0401 B83521 (A68-Cw4-B35) (Terena) A6802-B35 - A6802-B3501 Guadalahara. - A6802-B3502 Guadalahara. A68-B35 Mayan (A6803). These two haplotypes are consistent with the presence of Cw4-B35 and A68 in Asia and Middle East and A68-B35 maybe the ancestral A68 haplotype. A28(A6802)-B35 is found in Senegal. A6801-B4002/4 - Terena, Eskimo, Mestizo, Tribal Indians (Asia) A680102-B520102 in the Mexican Mestizo population. A28(A*6802)-B52 is also found in Senegal. ### Old World A68 haplotypes A28(~A68)-B51 Armenia, Senegal, Eskimo A28(~A68)-B70 W. Afr, Zaire, Zimbabwe, N. and S. African (Non-caucasians), Khoi (Hottentot)	HLA-A68 HLA-A68 (A68) is an HLA-A serotype. The serotype is a split antigen serotype also recognized by the broad antigen serotype A28. The closely related A6901 is derived, by recombination from A68. # Serotype # Disease Associations ### By allele A68 is associated with higher viral load in HIV[2] [3]. A68 may be protective against symptomatic heart disease in Chaga's cardiomyopathy.[4] # Allele freqeuncies A68 can be subdivided into 3 alleles, 6801, 6802, 6803. 6801 can also be subdivided into 680101 and 680102 (previously called 68011 and 68012). ### A6801 A6801 is higher in certain Native American groups, South Asian peoples, African peoples, however 6801 is at low levels in most of SE Asia, particularly the indigeonous populations. This is also reflected by low levels along the West Pacific Rim including Japan. The hiatus of 6801 breaks in Northern Japan with the 3% frequency found in the Ainu, which continues to increase with Arctic peoples and and falls of in Native Americans. Whereas in the Western Eurasia's northern regions, A6801 falls off. In both Africa and the New World both A680101 and A680102 can be found.[5] Although in the New World A680102 is more prevalent. ### A6802 A6802 has a global node within certain native peoples of South America, at 37%. A secondary node can be found in Africa. Like 6801 there is an hiatus of 6802 in SE Asia's indigeonous populations, indicating that this population is not a likely source within the native peoples of the New World. Levels are generally low (<1%) in Europe except along the Mediterranean coast. In Africa, higher levels can be found in Kenya and in Western Africa and the Cape Verde Islands.[5] A note on purity, the notion that A6802 is of indigeonous native American origin can be challenged based on possibility of introgression from Europeans and Africans. In the case of the Yucpa this is not teneble. The Yucpa have an HLA-DQ8 frequency of ~80%, the highest DQ allele frequency in the world, this tribe shows little evidence of European genetic introgression, in addition the closest DQ8 frequency in terms of Africa are the isolated !Kung of Namibia. There are two possible sources of A6802: Africa direct and Africa via Asia. The associated B alleles (B48, B61) point toward and Asian origin or an African source of very ancient origin, since time would be required to recombine Asian typical B alleles with A68. In the Spanish, A28 levels are 3.1% of this ~0.5% is A6901, A6802 is about 2.0% which means the net level of A6802 to A6805 in the Spanish is ~0.5%. Of 11 NA groups surveyed 9 are above and 2 are below 0.5%. Of the two Spanish groups 1 (Andalusia - 1.5%) is above and the other (Catalon 0.0%) is below. In an admixture model Spanish introgression does not explain A6802 in the New World. The Asian model of migration shows no single people NE of Pakistan that has A6802. ### A6803 A6803 can be found in native peoples of the New World and in Central Asia, in Africa it appears to be limited to West and Central Africans. This distribution along with the information on 6801 and 6802 suggests a probable redistribution of 68 alleles from Africa after the initial migration from East Africa that colonized Southeast Asia. It also provides support for 2 waves of migration from Asia to the New World or, at minimum, an unknown mixing area of West Pacific Rim haplotypes and West African/Middle Eastern derived haplotypes in Eastern Asia before the first migration. At present the incursion of Western Eurasian peoples into East Asia follows evidence for reuse of transbiakal region after 18,300 years and correlates with the insipient Jomon period of Japan several thousands of years later. Certain alleles and haplotypes of HLA in South Americans target Japans estimated pre-Yayoi composition, but other peoples, for example in western Mexico are most similar to the Ainu and the peoples of the Amur basin. ### A6805 A6805 is found in the Guatemalan and Central African Mbenzele at low levels. # A68 haplotypes The genetic distance between Native Americans and Eurasians is too great for the persistence of shared haplotypes, particularly in light of the lower levels in most of Siberia. The link of haplotypes with Western Africa may be significant, and may indicate a rapid eastward migration and admixing within the late paleolithic period. ### Indigeonous American haplotypes A680102-B35 haplotypes - A680102 Cw0304 B3506 (A68-Cw10-B35) - A68-Cw4-B35 (Terena, Seri (Mexico)) A680102 Cw0401 B83521 (A68-Cw4-B35) (Terena) - A680102 Cw0401 B83521 (A68-Cw4-B35) (Terena) A6802-B35 - A6802-B3501 Guadalahara. - A6802-B3502 Guadalahara. A68-B35 Mayan (A6803). These two haplotypes are consistent with the presence of Cw4-B35 and A68 in Asia and Middle East and A68-B35 maybe the ancestral A68 haplotype. A28(A6802)-B35 is found in Senegal.[21] A6801-B4002/4 - Terena, Eskimo, Mestizo, Tribal Indians (Asia) A680102-B520102 in the Mexican Mestizo population. A28(A*6802)-B52 is also found in Senegal.[21] ### Old World A68 haplotypes A28(~A68)-B51 Armenia, Senegal, Eskimo [21] A28(~A68)-B70 W. Afr, Zaire, Zimbabwe, N. and S. African (Non-caucasians), Khoi (Hottentot)[21]	https://www.wikidoc.org/index.php/HLA-A68
add82c43464296ba04cf2ae6c1ce41b03cb00f1b	wikidoc	HLA-A80	HLA-A80 HLA-A80 (A80) is the least common HLA-A group. The serotype identifies the more common HLA-A8001 gene product. A80 is almost exclusively found in africa and recent immigrants groups from West Africa # Serotype HLA-A80 typing is poor. Most typing is done with SSP-PCR. Most of 8001 are detected with "Blank" serotype. # Distribution and References - ↑ derived from IMGT/HLA - ↑ Jump up to: 2.0 2.1 Torimiro JN, Carr JK, Wolfe ND; et al. (2006). "HLA class I diversity among rural rainforest inhabitants in Cameroon: identification of A2612-B*4407 haplotype". Tissue Antigens. 67 (1): 30–7. doi:10.1111/j.1399-0039.2005.00527.x. PMID 16451198.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link) .mw-parser-output cite.citation{font-style:inherit}.mw-parser-output q{quotes:"\"""\"""'""'"}.mw-parser-output code.cs1-code{color:inherit;background:inherit;border:inherit;padding:inherit}.mw-parser-output .cs1-lock-free a{background:url("")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-limited a,.mw-parser-output .cs1-lock-registration a{background:url("")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-subscription a{background:url("")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration{color:#555}.mw-parser-output .cs1-subscription span,.mw-parser-output .cs1-registration span{border-bottom:1px dotted;cursor:help}.mw-parser-output .cs1-hidden-error{display:none;font-size:100%}.mw-parser-output .cs1-visible-error{display:none;font-size:100%}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration,.mw-parser-output .cs1-format{font-size:95%}.mw-parser-output .cs1-kern-left,.mw-parser-output .cs1-kern-wl-left{padding-left:0.2em}.mw-parser-output .cs1-kern-right,.mw-parser-output .cs1-kern-wl-right{padding-right:0.2em} - ↑ Modiano D, Luoni G, Petrarca V; et al. (2001). "HLA class I in three West African ethnic groups: genetic distances from sub-Saharan and Caucasoid populations". Tissue Antigens. 57 (2): 128–37. PMID 11260507.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link) {Template:WikiDoc Sources	HLA-A80 HLA-A80 (A80) is the least common HLA-A group. The serotype identifies the more common HLA-A8001 gene product. A80 is almost exclusively found in africa and recent immigrants groups from West Africa ### Serotype HLA-A80 typing is poor. Most typing is done with SSP-PCR. Most of 8001 are detected with "Blank" serotype. ### Distribution and References - ↑ derived from IMGT/HLA - ↑ Jump up to: 2.0 2.1 Torimiro JN, Carr JK, Wolfe ND; et al. (2006). "HLA class I diversity among rural rainforest inhabitants in Cameroon: identification of A2612-B*4407 haplotype". Tissue Antigens. 67 (1): 30–7. doi:10.1111/j.1399-0039.2005.00527.x. PMID 16451198.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link) .mw-parser-output cite.citation{font-style:inherit}.mw-parser-output q{quotes:"\"""\"""'""'"}.mw-parser-output code.cs1-code{color:inherit;background:inherit;border:inherit;padding:inherit}.mw-parser-output .cs1-lock-free a{background:url("https://upload.wikimedia.org/wikipedia/commons/thumb/6/65/Lock-green.svg/9px-Lock-green.svg.png")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-limited a,.mw-parser-output .cs1-lock-registration a{background:url("https://upload.wikimedia.org/wikipedia/commons/thumb/d/d6/Lock-gray-alt-2.svg/9px-Lock-gray-alt-2.svg.png")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-subscription a{background:url("https://upload.wikimedia.org/wikipedia/commons/thumb/a/aa/Lock-red-alt-2.svg/9px-Lock-red-alt-2.svg.png")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration{color:#555}.mw-parser-output .cs1-subscription span,.mw-parser-output .cs1-registration span{border-bottom:1px dotted;cursor:help}.mw-parser-output .cs1-hidden-error{display:none;font-size:100%}.mw-parser-output .cs1-visible-error{display:none;font-size:100%}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration,.mw-parser-output .cs1-format{font-size:95%}.mw-parser-output .cs1-kern-left,.mw-parser-output .cs1-kern-wl-left{padding-left:0.2em}.mw-parser-output .cs1-kern-right,.mw-parser-output .cs1-kern-wl-right{padding-right:0.2em} - ↑ Modiano D, Luoni G, Petrarca V; et al. (2001). "HLA class I in three West African ethnic groups: genetic distances from sub-Saharan and Caucasoid populations". Tissue Antigens. 57 (2): 128–37. PMID 11260507.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link) {Template:WikiDoc Sources	https://www.wikidoc.org/index.php/HLA-A80
d8327af7e0c7044307615c86137c9f64fda881f3	wikidoc	HLA-B46	HLA-B46 HLA-B46 (B46) is an HLA-B serotype. The serotype identifies the gene products of HLA-B4601 allele. B4601 resulted from a rare, interlocus, gene conversion between B62, probably B1501, and a HLA-C allele. B4601 is the most common HLA-B allele that does not have an origin within Africa, and estimated 400 million people in Eastern Asia carry a B46 allele. When found B4601 segregates with only 2 HLA-Cw alleles, A limited number of HLA-A and HLA-DRB1 alleles suggesting that the allele recently expanded from a limited sized group within SE Asia. Extremely low frequencies outside of Eastern Asia are indicators of a recent expansion of B46 from a recently small population. The frequency distribution suggests the ancestral B46 population was in SE China, or, potentially Burma (Myanmar or Laos, untested). B46 in asia correlates with wet-rice farming. The exceptions are notable, it has been found in the Nivkhi on north-eastern Sakalin Island, the Ainu, and the Nivkhi-related (genetically) Tlinglet population of Alaska at trace levels. (For terminology help see: HLA-serotype tutorial) # Serotype The serotyping is poor for B4601 and it is preferable to use SSP-PCR. # B4601 Allele Frequencies ## A2-Cw11(1)-B46 This haplotype is unique in several regards, first and most importantly the B46 serotype is not from Africa, this distinquishes it from every other known B serotype. It is the result of a recombination event between B62(B1501) and an HLA-C allele within Asia. This event happened recently as there is only one major allele and minor alleles are at trace frequencies. There has been some recombination between this haplotype, A24 and A11 bearing alleles, probably in a local (or tribal population). B46 is found wherever Asian wet-rice farming peoples have traveled and is found at low frequencies in non-farming indigeonous groups. The one exception is the Ninhvet of Siberia and the Eastern Tlinglet of Alaska. This B46 contribution appears to have been recent. Because of the numbers of people represented by the sample groups, and its relative high frequency in those group A2-B46 is one of the most frequent, if not the most frequent A-B haplotype in the world, even though it is absent from the indigeonous populations of most peoples in the world. This haplotype is unique in several regards, first and most importantly the B46 serotype is not from Africa, this distinquishes it from every other major B serotype except B48. It is the result of a recombination event between B62(B1501) and an HLA-C allele within Asia. This event happened recently as there is only one major allele and minor alleles are at trace frequencies. There has been some recombination between this haplotype, A24 and A11 bearing alleles, probably in a local (or tribal population). B46 is found wherever Asian wet-rice farming peoples have traveled and is found at low frequencies in non-farming indigeonous groups. The one exception is the Ninhvet of Siberia and the Eastern Tlinglet of Alaska. This B46 contribution appears to have been recent. Because of the numbers of people represented by the sample groups, and its relative high frequency in those group A2-B46 is one of the most frequent, if not the most frequent A-B haplotype in the world, even though it is absent from the indigeonous populations of most peoples in the world. The most common haplotype, and probably the ancestral haplotype given its distribution from the Ninhivet to Indonesia is: A0207 : C0102 : B4601 : DRB10901 : DQA10302 : DQB10303 A different haplotype that is more common in Korea and Japan is A0207 : C0102 : B4601 : DRB10803 : DQA10103 : DQB10601 B46, or a closely linked allele may have been under positive selection in rice farmers of Asia.	HLA-B46 HLA-B46 (B46) is an HLA-B serotype. The serotype identifies the gene products of HLA-B4601 allele.[1] B4601 resulted from a rare, interlocus, gene conversion between B62, probably B1501, and a HLA-C allele.[2] B4601 is the most common HLA-B allele that does not have an origin within Africa, and estimated 400 million people in Eastern Asia carry a B46 allele. When found B4601 segregates with only 2 HLA-Cw alleles, A limited number of HLA-A and HLA-DRB1 alleles suggesting that the allele recently expanded from a limited sized group within SE Asia. Extremely low frequencies outside of Eastern Asia are indicators of a recent expansion of B46 from a recently small population. The frequency distribution suggests the ancestral B46 population was in SE China, or, potentially Burma (Myanmar or Laos, untested). B46 in asia correlates with wet-rice farming. The exceptions are notable, it has been found in the Nivkhi on north-eastern Sakalin Island, the Ainu, and the Nivkhi-related (genetically) Tlinglet population of Alaska at trace levels. (For terminology help see: HLA-serotype tutorial) # Serotype The serotyping is poor for B4601 and it is preferable to use SSP-PCR. # B4601 Allele Frequencies ## A2-Cw11(1)-B46 This haplotype is unique in several regards, first and most importantly the B46 serotype is not from Africa, this distinquishes it from every other known B serotype. It is the result of a recombination event between B62(B1501) and an HLA-C allele within Asia. This event happened recently as there is only one major allele and minor alleles are at trace frequencies. There has been some recombination between this haplotype, A24 and A11 bearing alleles, probably in a local (or tribal population). B46 is found wherever Asian wet-rice farming peoples have traveled and is found at low frequencies in non-farming indigeonous groups. The one exception is the Ninhvet of Siberia and the Eastern Tlinglet of Alaska. This B46 contribution appears to have been recent. Because of the numbers of people represented by the sample groups, and its relative high frequency in those group A2-B46 is one of the most frequent, if not the most frequent A-B haplotype in the world, even though it is absent from the indigeonous populations of most peoples in the world. This haplotype is unique in several regards, first and most importantly the B46 serotype is not from Africa, this distinquishes it from every other major B serotype except B48. It is the result of a recombination event between B62(B1501) and an HLA-C allele within Asia. This event happened recently as there is only one major allele and minor alleles are at trace frequencies. There has been some recombination between this haplotype, A24 and A11 bearing alleles, probably in a local (or tribal population). B46 is found wherever Asian wet-rice farming peoples have traveled and is found at low frequencies in non-farming indigeonous groups. The one exception is the Ninhvet of Siberia and the Eastern Tlinglet of Alaska. This B46 contribution appears to have been recent. Because of the numbers of people represented by the sample groups, and its relative high frequency in those group A2-B46 is one of the most frequent, if not the most frequent A-B haplotype in the world, even though it is absent from the indigeonous populations of most peoples in the world. The most common haplotype, and probably the ancestral haplotype given its distribution from the Ninhivet to Indonesia is: A0207 : C0102 : B4601 : DRB10901 : DQA10302 : DQB10303 A different haplotype that is more common in Korea and Japan is A0207 : C0102 : B4601 : DRB10803 : DQA10103 : DQB10601 B46, or a closely linked allele may have been under positive selection in rice farmers of Asia.	https://www.wikidoc.org/index.php/HLA-B46
d1675befe007a39c3f56e515d01d24002b68f3e4	wikidoc	HLA-B47	HLA-B47 HLA-B47 (B47) is an HLA-B serotype. The serotype identifies the HLA-B47 gene products (B4701, B4702, B4703) . Comparison of B47 nucleotide sequence with other HLA-B sequences shows a segment of 228 bp identical with B44 in the alpha 1 domain and a segment of 218 bp identical with B27 in the alpha 2 domain, but only a 91 bp segment of identity with B13 in the alpha 1 domain. The complex pattern of substitutions and their degree of divergence indicate that HLA-B13 and HLA-Bw47 alleles are not related by a simple mutational event. B47 is linked to (close to on the chromosome) a gene that causes adrenal deficiency. B47 is generally low in frequency and with highest known frequencies in Central and Western Africa. (For terminology help see: HLA-serotype tutorial) # Serotype Serotyping for B47 is poor and typing is best performed with SSP-PCR or gene sequencing. # Disease Associations B47 is linked to Adrenal 21-hydroxylase deficiency. The CYP21 gene is located close to B47 between HLA-B and HLA-DRB1 locus. # B*4701 frequencies	HLA-B47 HLA-B47 (B47) is an HLA-B serotype. The serotype identifies the HLA-B47 gene products (B4701, B4702, B4703) .[1] Comparison of B47 nucleotide sequence with other HLA-B sequences shows a segment of 228 bp identical with B44 in the alpha 1 domain and a segment of 218 bp identical with B27 in the alpha 2 domain, but only a 91 bp segment of identity with B13 in the alpha 1 domain. The complex pattern of substitutions and their degree of divergence indicate that HLA-B13 and HLA-Bw47 alleles are not related by a simple mutational event.[2] B47 is linked to (close to on the chromosome) a gene that causes adrenal deficiency. B47 is generally low in frequency and with highest known frequencies in Central and Western Africa. (For terminology help see: HLA-serotype tutorial) # Serotype Serotyping for B47 is poor and typing is best performed with SSP-PCR or gene sequencing. # Disease Associations B47 is linked to Adrenal 21-hydroxylase deficiency.[2] The CYP21 gene is located close to B47 between HLA-B and HLA-DRB1 locus. # B*4701 frequencies	https://www.wikidoc.org/index.php/HLA-B47
ccabd23f1554c7baec1972387ebce75efdb71d99	wikidoc	HLA-B48	HLA-B48 HLA-B48 (B48) is an HLA-B serotype. The serotype identifies the more common HLA-B48 gene products. B48 is most common along the West Pacific Rim, Americas indigeonous peoples and Northern Eurasians. B4801 is part of a group of alleles including B4201 that share Intron 1 sequence with B0702, which is common over Western and Central Asia, and has a distribution indicating an early and long presence in Eurasian humans. A48 appears to be the result of a recombination event that occurred early in the settlement history of Central Asia that then spread eastward into the NW Pacific rim and the New World. (For terminology help see: HLA-serotype tutorial) # Serotype # Alleles # Haplotypes There is a known haplotype that covers a distance from South America to Siberia A2402 : C08 : B4801 : DRB108 : DQA10401 : DQB10402 and maybe indicative of recent long range migration. This haplotype is found in Peru, Mexico, Eskimos. The A2402 : C0801 : B4801 sub-component is also found in Asian Americans, Hispanic Americans, Indigeonous Taiwanese, Northern Philippines, Japanese, Orochon, Tibetians. The A-Cw-B component of the haplotype appears to have been conserved, however, equilibration of linkage to DR-DQ is more evident in Asian and Native American populations. The Cw0803 allelic variant of this haplotype is found in Japan, Eskimos, Asian Americans, Hispanic Americans and Oaxacans. The oddity of the distribution is that, other than the Manchu of Northern China, the Chinese population is devoid of the major A24-B48 and A2-B48 haplotypes. This indicates gene-flow along the West Pacific Rim to the New World and across Siberia connecting Tibet and Japan. B48 is found higher in the Ainu and Nivkhi than Japanese. Another haplotype that shows long distance relationships is the A0206 : C0801 : B4801 This haplotype is seen in the Taiwan aboriginal population, Okinawan, Japanese, Asian Americans, Orochon, Korean and Hispanic American populations. This haplotype might be extended with DRB10407 : DQA10301 : DQB10302 The Cw8-B48-DRB10407-DQB10302 is found in the Peru Llamas and Japanese populations. However levels in Japan, given the declining gradient to the south, indicate these haplotypes are the result of admixing with Northern Jomon populations during the post-Jomon period. The B48 haplotypes indicate that the Sea of Japan region was a probable hot spot for both migration to the South and also to the New World. The Orochon, which have the highest level of A24-B48 live along the Amur river in NE China and share many similarities with the Ainu of Hokkaido and the Nivkhi of Northern Sakalin Island. HLA B*48 haplotypes indicate a means of passage to the New World along the Siberian Coast, a possible land route of passage through Beringia or later by boat across the bering strait into the New World.	HLA-B48 HLA-B48 (B48) is an HLA-B serotype. The serotype identifies the more common HLA-B48 gene products.[1] B48 is most common along the West Pacific Rim, Americas indigeonous peoples and Northern Eurasians. B4801 is part of a group of alleles including B4201 that share Intron 1 sequence with B0702,[2] which is common over Western and Central Asia, and has a distribution indicating an early and long presence in Eurasian humans. A48 appears to be the result of a recombination event that occurred early in the settlement history of Central Asia that then spread eastward into the NW Pacific rim and the New World. (For terminology help see: HLA-serotype tutorial) # Serotype # Alleles # Haplotypes There is a known haplotype that covers a distance from South America to Siberia A2402 : C08 : B4801 : DRB108 : DQA10401 : DQB10402 and maybe indicative of recent long range migration. This haplotype is found in Peru, Mexico, Eskimos. The A2402 : C0801 : B4801 sub-component is also found in Asian Americans, Hispanic Americans, Indigeonous Taiwanese, Northern Philippines, Japanese, Orochon, Tibetians. The A-Cw-B component of the haplotype appears to have been conserved, however, equilibration of linkage to DR-DQ is more evident in Asian and Native American populations. The Cw0803 allelic variant of this haplotype is found in Japan, Eskimos, Asian Americans, Hispanic Americans and Oaxacans. The oddity of the distribution is that, other than the Manchu of Northern China, the Chinese population is devoid of the major A24-B48 and A2-B48 haplotypes. This indicates gene-flow along the West Pacific Rim to the New World and across Siberia connecting Tibet and Japan. B48 is found higher in the Ainu and Nivkhi than Japanese. Another haplotype that shows long distance relationships is the A0206 : C0801 : B4801 This haplotype is seen in the Taiwan aboriginal population, Okinawan, Japanese, Asian Americans, Orochon, Korean and Hispanic American populations. This haplotype might be extended with DRB10407 : DQA10301 : DQB10302 The Cw8-B48-DRB10407-DQB10302 is found in the Peru Llamas and Japanese populations. However levels in Japan, given the declining gradient to the south, indicate these haplotypes are the result of admixing with Northern Jomon populations during the post-Jomon period. The B48 haplotypes indicate that the Sea of Japan region was a probable hot spot for both migration to the South and also to the New World. The Orochon, which have the highest level of A24-B48 live along the Amur river in NE China and share many similarities with the Ainu of Hokkaido and the Nivkhi of Northern Sakalin Island. HLA B*48 haplotypes indicate a means of passage to the New World along the Siberian Coast, a possible land route of passage through Beringia or later by boat across the bering strait into the New World.	https://www.wikidoc.org/index.php/HLA-B48
63610dceb81f308f759c43ad191f894f9a473ca9	wikidoc	HLA-B81	HLA-B81 HLA-B81 (B81) is an HLA-B serotype. The serotype identifies the HLA-B8101 and B8102 (very rare) gene products. B81 is more common in Subsaharan Africa. While there is a B81 serotype, serotyping of B81 is poor when simultaneously tested with anti-B7 or B48 antibodies. (For terminology help see: HLA-serotype tutorial) # Serotype The serotype recognition of B8101 is poor and is best identified by genetic techniques such as SSP-PCR and gene sequencing. # Allele frequencies HLA-B81 corresponds to a single allele B8101. There are no characterized haplotypes of this allele that span multiple regions, though rare haplotypes certainly exist. The frequency in Kenya, Zimbabwe and Cameroon suggest that B81 probably expanded from core groups of Africans in Tanzania, Zambia or the Congo but with a limited spread do to its initial low frequency.	HLA-B81 HLA-B81 (B81) is an HLA-B serotype. The serotype identifies the HLA-B8101 and B8102 (very rare) gene products.[1] B81 is more common in Subsaharan Africa. While there is a B81 serotype, serotyping of B81 is poor when simultaneously tested with anti-B7 or B48 antibodies.[2] (For terminology help see: HLA-serotype tutorial) # Serotype The serotype recognition of B8101 is poor and is best identified by genetic techniques such as SSP-PCR and gene sequencing. # Allele frequencies HLA-B81 corresponds to a single allele B8101. There are no characterized haplotypes of this allele that span multiple regions, though rare haplotypes certainly exist. The frequency in Kenya, Zimbabwe and Cameroon suggest that B81 probably expanded from core groups of Africans in Tanzania, Zambia or the Congo but with a limited spread do to its initial low frequency.	https://www.wikidoc.org/index.php/HLA-B81
a9137e2ca1c6302da69835966b3e72809f80409a	wikidoc	HLA-DMB	HLA-DMB HLA class II histocompatibility antigen, DM beta chain is a protein that in humans is encoded by the HLA-DMB gene. # Function HLA-DMB belongs to the HLA class II beta chain paralogues. This class II molecule is a heterodimer consisting of an alpha (DMA) and a beta (DMB) chain, both anchored in the membrane. It is located in intracellular vesicles. DM plays a central role in the peptide loading of MHC class II molecules by helping to release the CLIP (class II-associated invariant chain peptide) molecule from the peptide binding site. Class II molecules are expressed in antigen presenting cells (APC: B lymphocytes, dendritic cells, macrophages). The beta chain is approximately 26-28 kDa and its gene contains 6 exons. Exon one encodes the leader peptide, exons 2 and 3 encode the two extracellular domains, exon 4 encodes the transmembrane domain and exon 5 encodes the cytoplasmic tail. # Clinical significance HLA-DMB is upregulated in tumor tissue of Caucasian but not African patients. Its role in tumor immunology is undefined but has been shown to positively correlated with increased T-cell infiltration and improved prognosis in ovarian cancer. Differential immune processes mediated by HLA-DMB may contribute to the disparity in cancer outcome.	HLA-DMB HLA class II histocompatibility antigen, DM beta chain is a protein that in humans is encoded by the HLA-DMB gene.[1][2] # Function HLA-DMB belongs to the HLA class II beta chain paralogues. This class II molecule is a heterodimer consisting of an alpha (DMA) and a beta (DMB) chain, both anchored in the membrane. It is located in intracellular vesicles. DM plays a central role in the peptide loading of MHC class II molecules by helping to release the CLIP (class II-associated invariant chain peptide) molecule from the peptide binding site. Class II molecules are expressed in antigen presenting cells (APC: B lymphocytes, dendritic cells, macrophages). The beta chain is approximately 26-28 kDa and its gene contains 6 exons. Exon one encodes the leader peptide, exons 2 and 3 encode the two extracellular domains, exon 4 encodes the transmembrane domain and exon 5 encodes the cytoplasmic tail.[2] # Clinical significance HLA-DMB is upregulated in tumor tissue of Caucasian but not African patients. Its role in tumor immunology is undefined but has been shown to positively correlated with increased T-cell infiltration and improved prognosis in ovarian cancer. Differential immune processes mediated by HLA-DMB may contribute to the disparity in cancer outcome.[3]	https://www.wikidoc.org/index.php/HLA-DMB
c6474b4893a4a879948c1030e4bf94b14eb3fef8	wikidoc	HLA-DR1	HLA-DR1 HLA-DR1 (DR1) is a HLA-DR serotype that recognizes the DRB101 gene products. # Serology The serology for the most popular DR1 alleles is excellent. The serology for alleles 0104, 0106, 0109, 0110, 0112, 0115, and 0116 is unknown. # Disease Associations ## By serotype DR1 is associated seronegative-rheumatoid arthritis, penicillamine-induced myasthenia, and schizophrenia. DR1 is increased in patients with systemic schlerosis and arthritis and in ulcerative colitis with patients that have articular manifestations. ## By allele DRB10101 is associated with rheumatoid arthritis, in anti-Jk(a) mediated hemolytic transfusion reactions, foliaceous pemphigus, HTLV-1-associated myelopathy/tropical spastic paraparesis, and lichen planus. In lyme disease arthritis, 0101 appears to play a role in presentation of triggering microbial antigens. DRB10102 is associated with rheumatoid arthritis, in anti-Jk(a) mediated hemolytic transfusion reactions, psoriasis vulgaris, and recurrent respiratory papillomatosis DRB10103 is associated with colonic Crohn's disease and ulcerative colitis. ## By genotype DRB10101/0404 and 0101/0401 increases risk of mortality in rheumatoid arthritis, with ischemic heart disease and smoking. these same genotypes are associated with rheumatoid vasculitis. ## By haplotype DRB10102:DQB10501 is associated with psoriasis vulgaris and tubulointerstitial nephritis & uveitis syndrome, but is relatively protective against juvenile diabetes. DR1-DQ5 is associate with tubulointerstitial nephritis & uveitis syndrome. # Rheumatoid Arthritis DR1 are associated with rheumatoid arthritis, and while not the strongest association with the highest risk for early onset arthritis is within the DR4 bearing native american population. There frequency of DR4-DQ8 haplotypes reach extreme nodal levels. Arthritis has been identified in a precolumbian remains from Italy, the affected individual bearing the DRB10101 allele. DRB10101 and most DR4 have in common a 'shared epitope'.. In this hypothesis a common region of the beta chain, positions 67 to 74, are common and may be integral to presenting auto-immunological peptides. # Genetic Linkage HLA-DR1 is not genetically linked to DR51, DR52 or DR53, but is linked to HLA-DQ1 and DQ5 serotypes. # references - ↑ Fernández MM, Guan R, Swaminathan CP, Malchiodi EL, Mariuzza RA (2006). "Crystal structure of staphylococcal enterotoxin I (SEI) in complex with a human major histocompatibility complex class II molecule". J. Biol. Chem. 281 (35): 25356–64. doi:10.1074/jbc.M603969200. PMID 16829512.CS1 maint: Multiple names: authors list (link) .mw-parser-output cite.citation{font-style:inherit}.mw-parser-output q{quotes:"\"""\"""'""'"}.mw-parser-output code.cs1-code{color:inherit;background:inherit;border:inherit;padding:inherit}.mw-parser-output .cs1-lock-free a{background:url("")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-limited a,.mw-parser-output .cs1-lock-registration a{background:url("")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-subscription a{background:url("")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration{color:#555}.mw-parser-output .cs1-subscription span,.mw-parser-output .cs1-registration span{border-bottom:1px dotted;cursor:help}.mw-parser-output .cs1-hidden-error{display:none;font-size:100%}.mw-parser-output .cs1-visible-error{display:none;font-size:100%}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration,.mw-parser-output .cs1-format{font-size:95%}.mw-parser-output .cs1-kern-left,.mw-parser-output .cs1-kern-wl-left{padding-left:0.2em}.mw-parser-output .cs1-kern-right,.mw-parser-output .cs1-kern-wl-right{padding-right:0.2em} - ↑ derived from IMGT/HLA - ↑ Bardin T, Legrand L, Naveau B, Marcelli-Barge A, Debeyre N, Lathrop G, Poirier J, Schmid M, Ryckewaert A, Dryll A (1985). "HLA antigens and seronegative rheumatoid arthritis". Ann Rheum Dis. 44 (1): 50–3. PMID 3855618.CS1 maint: Multiple names: authors list (link) - ↑ Schiff B, Mizrachi Y, Orgad S, Yaron M, Gazit E (1982). "Association of HLA-Aw31 and HLA-DR1 with adult rheumatoid arthritis". Ann Rheum Dis. 41 (4): 403–4. PMID 6981387.CS1 maint: Multiple names: authors list (link) - ↑ "HLA-DR antigens in rheumatoid arthritis. A Swiss collaborative study; final report. Swiss Federal Commission for the Rheumatic Diseases, Subcommission for Research". Rheumatol Int. 6 (2): 89–92. 1986. PMID 3489975. - ↑ Delamere J, Jobson S, Mackintosh L, Wells L, Walton K (1983). "Penicillamine-induced myasthenia in rheumatoid arthritis: its clinical and genetic features". Ann Rheum Dis. 42 (5): 500–4. PMID 6605118.CS1 maint: Multiple names: authors list (link) - ↑ Narita K, Sasaki T, Akaho R, Okazaki Y, Kusumi I, Kato T, Hashimoto O, Fukuda R, Koyama T, Matsuo K, Okabe Y, Nanko S, Hohjoh H, Tokunaga K (2000). "Human leukocyte antigen and season of birth in Japanese patients with schizophrenia". Am J Psychiatry. 157 (7): 1173–5. PMID 10873932.CS1 maint: Multiple names: authors list (link) - ↑ Szücs G, Szekanecz Z, Zilahi E; et al. (2007). "Systemic sclerosis-rheumatoid arthritis overlap syndrome: a unique combination of features suggests a distinct genetic, serological and clinical entity". Rheumatology (Oxford, England). 46 (6): 989–93. doi:10.1093/rheumatology/kem021. PMID 17384178.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link) - ↑ Núñez C, Alecsandru DM, Mendoza JL; et al. (2006). "Genetic markers linked to rheumatoid arthritis are also strongly associated with articular manifestations in ulcerative colitis patients". Hum. Immunol. 67 (4–5): 324–30. doi:10.1016/j.humimm.2006.02.035. PMID 16720213.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link) - ↑ Jump up to: 10.0 10.1 Kapitány A, Zilahi E, Szántó S; et al. (2005). "Association of rheumatoid arthritis with HLA-DR1 and HLA-DR4 in Hungary". Ann. N. Y. Acad. Sci. 1051: 263–70. doi:10.1196/annals.1361.067. PMID 16126967.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link) - ↑ Jump up to: 11.0 11.1 Reviron D, Dettori I, Ferrera V; et al. (2005). "HLA-DRB1 alleles and Jk(a) immunization". Transfusion. 45 (6): 956–9. doi:10.1111/j.1537-2995.2005.04366.x. PMID 15934994.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link) - ↑ del Mar Sáez-de-Ocariz M, Vega-Memije M, Zúñiga J, Salgado N, Ruíz J, Balbuena A, Domínguez-Soto L, Granados J (2005). "HLA-DRB10101 is associated with foliaceous pemphigus in Mexicans". Int J Dermatol. 44 (4): 350. PMID 15811100.CS1 maint: Multiple names: authors list (link) - ↑ Sabouri A, Saito M, Usuku K, Bajestan S, Mahmoudi M, Forughipour M, Sabouri Z, Abbaspour Z, Goharjoo M, Khayami E, Hasani A, Izumo S, Arimura K, Farid R, Osame M (2005). "Differences in viral and host genetic risk factors for development of human T-cell lymphotropic virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis between Iranian and Japanese HTLV-1-infected individuals". J Gen Virol. 86 (Pt 3): 773–81. PMID 15722539.CS1 maint: Multiple names: authors list (link) - ↑ Luis-Montoya P, Yamamoto-Furusho JK, Vega-Memije E; et al. (2007). "HLA-DRB10101 is associated with the genetic susceptibility to develop lichen planus in the Mexican Mestizo population". doi:10.1007/s00403-007-0769-2. PMID 17665209.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link) - ↑ Steere AC, Klitz W, Drouin EE; et al. (2006). "Antibiotic-refractory Lyme arthritis is associated with HLA-DR molecules that bind a Borrelia burgdorferi peptide". J. Exp. Med. 203 (4): 961–71. doi:10.1084/jem.20052471. PMID 16585267.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link) - ↑ Jump up to: 16.0 16.1 Cardoso C, Uthida-Tanaka A, Magalhães R, Magna L, Kraemer M. "Association between psoriasis vulgaris and MHC-DRB, -DQB genes as a contribution to disease diagnosis". Eur J Dermatol. 15 (3): 159–63. PMID 15908298.CS1 maint: Multiple names: authors list (link) - ↑ Bonagura V, Vambutas A, DeVoti J, Rosenthal D, Steinberg B, Abramson A, Shikowitz M, Gjertson D, Reed E (2004). "HLA alleles, IFN-gamma responses to HPV-11 E6, and disease severity in patients with recurrent respiratory papillomatosis". Hum Immunol. 65 (8): 773–82. PMID 15336778.CS1 maint: Multiple names: authors list (link) - ↑ Fernandez L, Mendoza J, Martinez A, Urcelay E, Fernandez-Arquero M, Garcia-Paredes J, Peña A, Diaz-Rubio M, de la Concha E (2004). "IBD1 and IBD3 determine location of Crohn's disease in the Spanish population". Inflamm Bowel Dis. 10 (6): 715–22. PMID 15626888.CS1 maint: Multiple names: authors list (link) - ↑ Puzanowska B, Prokopowicz D, Ziarko S, Radziwon P, Lapinski T. "The incidence of HLA DRB1*0103 in ulcerative colitis patients in north-eastern Poland". Hepatogastroenterology. 50 (53): 1436–8. PMID 14571756.CS1 maint: Multiple names: authors list (link) - ↑ Roussomoustakaki M, Satsangi J, Welsh K, Louis E, Fanning G, Targan S, Landers C, Jewell D (1997). "Genetic markers may predict disease behavior in patients with ulcerative colitis". Gastroenterology. 112 (6): 1845–53. PMID 9178675.CS1 maint: Multiple names: authors list (link) - ↑ Mattey DL, Thomson W, Ollier WE; et al. (2007). "Association of DRB1 shared epitope genotypes with early mortality in rheumatoid arthritis: results of eighteen years of followup from the early rheumatoid arthritis study". Arthritis Rheum. 56 (5): 1408–16. doi:10.1002/art.22527. PMID 17469097.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link) - ↑ Gorman JD, David-Vaudey E, Pai M, Lum RF, Criswell LA (2004). "Particular HLA-DRB1 shared epitope genotypes are strongly associated with rheumatoid vasculitis". Arthritis Rheum. 50 (11): 3476–84. doi:10.1002/art.20588. PMID 15529352.CS1 maint: Multiple names: authors list (link) - ↑ Jump up to: 23.0 23.1 >Levinson R, Park M, Rikkers S, Reed E, Smith J, Martin T, Rosenbaum J, Foster C, Sherman M, Holland G (2003). "Strong associations between specific HLA-DQ and HLA-DR alleles and the tubulointerstitial nephritis and uveitis syndrome". Invest Ophthalmol Vis Sci. 44 (2): 653–7. PMID 12556395.CS1 maint: Multiple names: authors list (link) - ↑ Thomson G, Valdes AM, Noble JA; et al. (2007). "Relative predispositional effects of HLA class II DRB1-DQB1 haplotypes and genotypes on type 1 diabetes: a meta-analysis". Tissue Antigens. 70 (2): 110–27. doi:10.1111/j.1399-0039.2007.00867.x. PMID 17610416.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link) - ↑ Fontecchio G, Fioroni MA, Azzarone R; et al. (2007). "Genetic predisposition to rheumatoid arthritis in a Tuscan (Italy) ancient human remain". International journal of immunopathology and pharmacology. 20 (1): 103–9. PMID 17346433.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link) - ↑ Gregersen PK, Silver J, Winchester RJ (1987). "The shared epitope hypothesis. An approach to understanding the molecular genetics of susceptibility to rheumatoid arthritis". Arthritis Rheum. 30 (11): 1205–13. PMID 2446635.CS1 maint: Multiple names: authors list (link) - ↑ Morel PA, Erlich HA, Fathman CG (1988). "A new look at the shared epitope hypothesis". Am. J. Med. 85 (6A): 20–2. PMID 2462347.CS1 maint: Multiple names: authors list (link)	HLA-DR1 HLA-DR1 (DR1) is a HLA-DR serotype that recognizes the DRB101 gene products. # Serology The serology for the most popular DR1 alleles is excellent. The serology for alleles 0104, 0106, 0109, 0110, 0112, 0115, and 0116 is unknown. # Disease Associations ## By serotype DR1 is associated seronegative[3]-rheumatoid arthritis[4][5], penicillamine-induced myasthenia[6], and schizophrenia[7]. DR1 is increased in patients with systemic schlerosis and arthritis[8] and in ulcerative colitis with patients that have articular manifestations.[9] ## By allele DRB10101 is associated with rheumatoid arthritis,[10] in anti-Jk(a) mediated hemolytic transfusion reactions,[11] foliaceous pemphigus,[12] HTLV-1-associated myelopathy/tropical spastic paraparesis, and [13] lichen planus[14]. In lyme disease arthritis, 0101 appears to play a role in presentation of triggering microbial antigens.[15] DRB10102 is associated with rheumatoid arthritis,[10] in anti-Jk(a) mediated hemolytic transfusion reactions,[11] psoriasis vulgaris[16], and recurrent respiratory papillomatosis[17] DRB10103 is associated with colonic Crohn's disease[18] and ulcerative colitis.[19][20] ## By genotype DRB10101/0404 and 0101/0401 increases risk of mortality in rheumatoid arthritis, with ischemic heart disease and smoking.[21] these same genotypes are associated with rheumatoid vasculitis.[22] ## By haplotype DRB10102:DQB10501 is associated with psoriasis vulgaris[16] and tubulointerstitial nephritis & uveitis syndrome[23], but is relatively protective against juvenile diabetes.[24] DR1-DQ5 is associate with tubulointerstitial nephritis & uveitis syndrome.[23] # Rheumatoid Arthritis DR1 are associated with rheumatoid arthritis, and while not the strongest association with the highest risk for early onset arthritis is within the DR4 bearing native american population. There frequency of DR4-DQ8 haplotypes reach extreme nodal levels. Arthritis has been identified in a precolumbian remains from Italy, the affected individual bearing the DRB10101 allele[25]. DRB10101 and most DR4 have in common a 'shared epitope'.[26][27]. In this hypothesis a common region of the beta chain, positions 67 to 74, are common and may be integral to presenting auto-immunological peptides. # Genetic Linkage HLA-DR1 is not genetically linked to DR51, DR52 or DR53, but is linked to HLA-DQ1 and DQ5 serotypes. # references - ↑ Fernández MM, Guan R, Swaminathan CP, Malchiodi EL, Mariuzza RA (2006). "Crystal structure of staphylococcal enterotoxin I (SEI) in complex with a human major histocompatibility complex class II molecule". J. Biol. Chem. 281 (35): 25356–64. doi:10.1074/jbc.M603969200. PMID 16829512.CS1 maint: Multiple names: authors list (link) .mw-parser-output cite.citation{font-style:inherit}.mw-parser-output q{quotes:"\"""\"""'""'"}.mw-parser-output code.cs1-code{color:inherit;background:inherit;border:inherit;padding:inherit}.mw-parser-output .cs1-lock-free a{background:url("https://upload.wikimedia.org/wikipedia/commons/thumb/6/65/Lock-green.svg/9px-Lock-green.svg.png")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-limited a,.mw-parser-output .cs1-lock-registration a{background:url("https://upload.wikimedia.org/wikipedia/commons/thumb/d/d6/Lock-gray-alt-2.svg/9px-Lock-gray-alt-2.svg.png")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-subscription a{background:url("https://upload.wikimedia.org/wikipedia/commons/thumb/a/aa/Lock-red-alt-2.svg/9px-Lock-red-alt-2.svg.png")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration{color:#555}.mw-parser-output .cs1-subscription span,.mw-parser-output .cs1-registration span{border-bottom:1px dotted;cursor:help}.mw-parser-output .cs1-hidden-error{display:none;font-size:100%}.mw-parser-output .cs1-visible-error{display:none;font-size:100%}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration,.mw-parser-output .cs1-format{font-size:95%}.mw-parser-output .cs1-kern-left,.mw-parser-output .cs1-kern-wl-left{padding-left:0.2em}.mw-parser-output .cs1-kern-right,.mw-parser-output .cs1-kern-wl-right{padding-right:0.2em} - ↑ derived from IMGT/HLA - ↑ Bardin T, Legrand L, Naveau B, Marcelli-Barge A, Debeyre N, Lathrop G, Poirier J, Schmid M, Ryckewaert A, Dryll A (1985). "HLA antigens and seronegative rheumatoid arthritis". Ann Rheum Dis. 44 (1): 50–3. PMID 3855618.CS1 maint: Multiple names: authors list (link) - ↑ Schiff B, Mizrachi Y, Orgad S, Yaron M, Gazit E (1982). "Association of HLA-Aw31 and HLA-DR1 with adult rheumatoid arthritis". Ann Rheum Dis. 41 (4): 403–4. PMID 6981387.CS1 maint: Multiple names: authors list (link) - ↑ "HLA-DR antigens in rheumatoid arthritis. A Swiss collaborative study; final report. Swiss Federal Commission for the Rheumatic Diseases, Subcommission for Research". Rheumatol Int. 6 (2): 89–92. 1986. PMID 3489975. - ↑ Delamere J, Jobson S, Mackintosh L, Wells L, Walton K (1983). "Penicillamine-induced myasthenia in rheumatoid arthritis: its clinical and genetic features". Ann Rheum Dis. 42 (5): 500–4. PMID 6605118.CS1 maint: Multiple names: authors list (link) - ↑ Narita K, Sasaki T, Akaho R, Okazaki Y, Kusumi I, Kato T, Hashimoto O, Fukuda R, Koyama T, Matsuo K, Okabe Y, Nanko S, Hohjoh H, Tokunaga K (2000). "Human leukocyte antigen and season of birth in Japanese patients with schizophrenia". Am J Psychiatry. 157 (7): 1173–5. PMID 10873932.CS1 maint: Multiple names: authors list (link) - ↑ Szücs G, Szekanecz Z, Zilahi E; et al. (2007). "Systemic sclerosis-rheumatoid arthritis overlap syndrome: a unique combination of features suggests a distinct genetic, serological and clinical entity". Rheumatology (Oxford, England). 46 (6): 989–93. doi:10.1093/rheumatology/kem021. PMID 17384178.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link) - ↑ Núñez C, Alecsandru DM, Mendoza JL; et al. (2006). "Genetic markers linked to rheumatoid arthritis are also strongly associated with articular manifestations in ulcerative colitis patients". Hum. Immunol. 67 (4–5): 324–30. doi:10.1016/j.humimm.2006.02.035. PMID 16720213.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link) - ↑ Jump up to: 10.0 10.1 Kapitány A, Zilahi E, Szántó S; et al. (2005). "Association of rheumatoid arthritis with HLA-DR1 and HLA-DR4 in Hungary". Ann. N. Y. Acad. Sci. 1051: 263–70. doi:10.1196/annals.1361.067. PMID 16126967.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link) - ↑ Jump up to: 11.0 11.1 Reviron D, Dettori I, Ferrera V; et al. (2005). "HLA-DRB1 alleles and Jk(a) immunization". Transfusion. 45 (6): 956–9. doi:10.1111/j.1537-2995.2005.04366.x. PMID 15934994.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link) - ↑ del Mar Sáez-de-Ocariz M, Vega-Memije M, Zúñiga J, Salgado N, Ruíz J, Balbuena A, Domínguez-Soto L, Granados J (2005). "HLA-DRB10101 is associated with foliaceous pemphigus in Mexicans". Int J Dermatol. 44 (4): 350. PMID 15811100.CS1 maint: Multiple names: authors list (link) - ↑ Sabouri A, Saito M, Usuku K, Bajestan S, Mahmoudi M, Forughipour M, Sabouri Z, Abbaspour Z, Goharjoo M, Khayami E, Hasani A, Izumo S, Arimura K, Farid R, Osame M (2005). "Differences in viral and host genetic risk factors for development of human T-cell lymphotropic virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis between Iranian and Japanese HTLV-1-infected individuals". J Gen Virol. 86 (Pt 3): 773–81. PMID 15722539.CS1 maint: Multiple names: authors list (link) - ↑ Luis-Montoya P, Yamamoto-Furusho JK, Vega-Memije E; et al. (2007). "HLA-DRB10101 is associated with the genetic susceptibility to develop lichen planus in the Mexican Mestizo population". doi:10.1007/s00403-007-0769-2. PMID 17665209.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link) - ↑ Steere AC, Klitz W, Drouin EE; et al. (2006). "Antibiotic-refractory Lyme arthritis is associated with HLA-DR molecules that bind a Borrelia burgdorferi peptide". J. Exp. Med. 203 (4): 961–71. doi:10.1084/jem.20052471. PMID 16585267.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link) - ↑ Jump up to: 16.0 16.1 Cardoso C, Uthida-Tanaka A, Magalhães R, Magna L, Kraemer M. "Association between psoriasis vulgaris and MHC-DRB, -DQB genes as a contribution to disease diagnosis". Eur J Dermatol. 15 (3): 159–63. PMID 15908298.CS1 maint: Multiple names: authors list (link) - ↑ Bonagura V, Vambutas A, DeVoti J, Rosenthal D, Steinberg B, Abramson A, Shikowitz M, Gjertson D, Reed E (2004). "HLA alleles, IFN-gamma responses to HPV-11 E6, and disease severity in patients with recurrent respiratory papillomatosis". Hum Immunol. 65 (8): 773–82. PMID 15336778.CS1 maint: Multiple names: authors list (link) - ↑ Fernandez L, Mendoza J, Martinez A, Urcelay E, Fernandez-Arquero M, Garcia-Paredes J, Peña A, Diaz-Rubio M, de la Concha E (2004). "IBD1 and IBD3 determine location of Crohn's disease in the Spanish population". Inflamm Bowel Dis. 10 (6): 715–22. PMID 15626888.CS1 maint: Multiple names: authors list (link) - ↑ Puzanowska B, Prokopowicz D, Ziarko S, Radziwon P, Lapinski T. "The incidence of HLA DRB1*0103 in ulcerative colitis patients in north-eastern Poland". Hepatogastroenterology. 50 (53): 1436–8. PMID 14571756.CS1 maint: Multiple names: authors list (link) - ↑ Roussomoustakaki M, Satsangi J, Welsh K, Louis E, Fanning G, Targan S, Landers C, Jewell D (1997). "Genetic markers may predict disease behavior in patients with ulcerative colitis". Gastroenterology. 112 (6): 1845–53. PMID 9178675.CS1 maint: Multiple names: authors list (link) - ↑ Mattey DL, Thomson W, Ollier WE; et al. (2007). "Association of DRB1 shared epitope genotypes with early mortality in rheumatoid arthritis: results of eighteen years of followup from the early rheumatoid arthritis study". Arthritis Rheum. 56 (5): 1408–16. doi:10.1002/art.22527. PMID 17469097.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link) - ↑ Gorman JD, David-Vaudey E, Pai M, Lum RF, Criswell LA (2004). "Particular HLA-DRB1 shared epitope genotypes are strongly associated with rheumatoid vasculitis". Arthritis Rheum. 50 (11): 3476–84. doi:10.1002/art.20588. PMID 15529352.CS1 maint: Multiple names: authors list (link) - ↑ Jump up to: 23.0 23.1 >Levinson R, Park M, Rikkers S, Reed E, Smith J, Martin T, Rosenbaum J, Foster C, Sherman M, Holland G (2003). "Strong associations between specific HLA-DQ and HLA-DR alleles and the tubulointerstitial nephritis and uveitis syndrome". Invest Ophthalmol Vis Sci. 44 (2): 653–7. PMID 12556395.CS1 maint: Multiple names: authors list (link) - ↑ Thomson G, Valdes AM, Noble JA; et al. (2007). "Relative predispositional effects of HLA class II DRB1-DQB1 haplotypes and genotypes on type 1 diabetes: a meta-analysis". Tissue Antigens. 70 (2): 110–27. doi:10.1111/j.1399-0039.2007.00867.x. PMID 17610416.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link) - ↑ Fontecchio G, Fioroni MA, Azzarone R; et al. (2007). "Genetic predisposition to rheumatoid arthritis in a Tuscan (Italy) ancient human remain". International journal of immunopathology and pharmacology. 20 (1): 103–9. PMID 17346433.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link) - ↑ Gregersen PK, Silver J, Winchester RJ (1987). "The shared epitope hypothesis. An approach to understanding the molecular genetics of susceptibility to rheumatoid arthritis". Arthritis Rheum. 30 (11): 1205–13. PMID 2446635.CS1 maint: Multiple names: authors list (link) - ↑ Morel PA, Erlich HA, Fathman CG (1988). "A new look at the shared epitope hypothesis". Am. J. Med. 85 (6A): 20–2. PMID 2462347.CS1 maint: Multiple names: authors list (link) Template:DR Template:WikiDoc Sources	https://www.wikidoc.org/index.php/HLA-DR1
cbca9cc67265fe83444555f51f582d3bdfedb72a	wikidoc	HLA-DRA	HLA-DRA HLA class II histocompatibility antigen, DR alpha chain is a protein that in humans is encoded by the HLA-DRA gene. HLA-DRA encodes the alpha subunit of HLA-DR. Unlike the alpha chains of other Human MHC class II molecules, the alpha subunit is practically invariable. However it can pair with, in any individual, the beta chain from 3 different DR beta loci, DRB1, and two of any DRB3, DRB4, or DRB5 alleles. Thus there is the potential that any given individual can form 4 different HLA-DR isoforms (2 alleles of DRB1 and two alleles from DRB3, DRB4 or DRB5). # Function The polypeptide subunit encoded by this gene belongs to the HLA class II alpha chain paralogues. The class II protein is a heterodimer consisting of an alpha (DRα) and a beta chain (DRβ), both anchored in the membrane. It plays a central role in the immune system by presenting peptides derived from extracellular proteins. Class II molecules are expressed in antigen presenting cells (APC: B lymphocytes, dendritic cells, macrophages). # Gene structure and polymorphisms The alpha chain is approximately 33-35 kDa and its gene contains 5 exons. Exon 1 encodes the leader peptide, exons 2 and 3 encode the two extracellular domains, and exon 4 encodes the transmembrane domain and the cytoplasmic tail. DRA does not have polymorphisms in the peptide binding part and acts as the sole alpha chain for DRB1, DRB3, DRB4 and DRB5. # Alleles There are two different HLA-DRA chains in the human population coded by three different DRA alleles:	HLA-DRA HLA class II histocompatibility antigen, DR alpha chain is a protein that in humans is encoded by the HLA-DRA gene.[1] HLA-DRA encodes the alpha subunit of HLA-DR. Unlike the alpha chains of other Human MHC class II molecules, the alpha subunit is practically invariable. However it can pair with, in any individual, the beta chain from 3 different DR beta loci, DRB1, and two of any DRB3, DRB4, or DRB5 alleles. Thus there is the potential that any given individual can form 4 different HLA-DR isoforms (2 alleles of DRB1 and two alleles from DRB3, DRB4 or DRB5). # Function The polypeptide subunit encoded by this gene belongs to the HLA class II alpha chain paralogues. The class II protein is a heterodimer consisting of an alpha (DRα) and a beta chain (DRβ), both anchored in the membrane. It plays a central role in the immune system by presenting peptides derived from extracellular proteins. Class II molecules are expressed in antigen presenting cells (APC: B lymphocytes, dendritic cells, macrophages).[1] # Gene structure and polymorphisms The alpha chain is approximately 33-35 kDa and its gene contains 5 exons. Exon 1 encodes the leader peptide, exons 2 and 3 encode the two extracellular domains, and exon 4 encodes the transmembrane domain and the cytoplasmic tail. DRA does not have polymorphisms in the peptide binding part and acts as the sole alpha chain for DRB1, DRB3, DRB4 and DRB5.[1] # Alleles There are two different HLA-DRA chains in the human population coded by three different DRA alleles:	https://www.wikidoc.org/index.php/HLA-DRA
33b97a82aa46cad774432a2fb30f8e48d8ba287c	wikidoc	Statins	Statins The statins (or HMG-CoA reductase inhibitors) form a class of hypolipidemic drugs used to lower cholesterol levels in people with or at risk of cardiovascular disease. They lower cholesterol by inhibiting the enzyme HMG-CoA reductase, which is the rate-limiting enzyme of the mevalonate pathway of cholesterol synthesis. Inhibition of this enzyme in the liver stimulates LDL receptors, resulting in an increased clearance of low-density lipoprotein (LDL) from the bloodstream and a decrease in blood cholesterol levels. The first results can be seen after one week of use and the effect is maximal after four to six weeks. # History Akira Endo and Masao Kuroda of Tokyo, Japan commenced research into inhibitors of HMG-CoA reductase in 1971 (Endo 1992). This team reasoned that certain microorganisms may produce inhibitors of the enzyme to defend themselves against other organisms, as mevalonate is a precursor of many substances required by organisms for the maintenance of their cell wall (ergosterol) or cytoskeleton (isoprenoids). The first agent isolated was mevastatin (ML-236B), a molecule produced by Penicillium citrinum. The pharmaceutical company Merck & Co. showed an interest in the Japanese research in 1976, and isolated lovastatin (mevinolin, MK803), the first commercially marketed statin, from the mold Aspergillus terreus. Dr Endo was awarded the 2006 Japan Prize for his work on the development of statins. # Indications and uses Statins, the most potent cholesterol-lowering agents available, lower LDL cholesterol (so-called "bad cholesterol") by 30–50%. However, they have less effect than the fibrates or niacin in reducing triglycerides and raising HDL-cholesterol ("good cholesterol"). Professional guidelines generally require that the patient has tried a cholesterol-lowering diet before statin use is considered; statins or other pharmacologic agents may then be recommended for patients who do not meet their lipid-lowering goals through diet and lifestyle approaches. The indications for the prescription of statins have broadened over the years. Initial studies, such as the Scandinavian Simvastatin Survival Study (4S), supported the use of statins in secondary prevention for cardiovascular disease, or as primary prevention only when the risk for cardiovascular disease was significantly raised (as indicated by the Framingham risk score). Indications were broadened considerably by studies such as the Heart Protection Study (HPS), which showed preventative effects of statin use in specific risk groups, such as diabetics. The ASTEROID trial, published in 2006, using only a statin at high dose, achieved lower than usual target calculated LDL values and showed disease regression within the coronary arteries using intravascular ultrasonography. Based on clinical trials, the National Cholesterol Education Program guidelines, and the increasing focus on aggressively lowering LDL-cholesterol, the statins continue to play an important role in both the primary and secondary prevention of coronary heart disease, myocardial infarction, stroke and peripheral artery disease. Research continues into other areas where statins also appear to have a favorable effect: inflammation, dementia, cancer, nuclear cataracts, and pulmonary hypertension. # Members The statins are divided into two groups: fermentation-derived and synthetic. The statins include, in alphabetical order (brand names vary in different countries): LDL-lowering potency varies between agents. Cerivastatin is the most potent, followed by (in order of decreasing potency) rosuvastatin, atorvastatin, simvastatin, lovastatin, pravastatin, and fluvastatin. The relative potency of pitavastatin has not yet been fully established. ## Comparative effectiveness No large scale comparison exists that examines the effectiveness of the various statins against one another. An independent analysis has been done to compare atorvastatin, pravastatin and simvastatin, based on their effectiveness against placebos. It found that, at commonly prescribed doses, there are no statistically significant differences in reducing cardiovascular morbidity and mortality. # Safety ## Adverse effects While some patients on statin therapy report myalgias, muscle cramps, or far less-frequent gastrointestinal or other symptoms, similar symptoms are also reported with placebo use in all the large statin safety/efficacy trials and usually resolve, either on their own or on temporarily lowering/stopping the dose. Liver enzyme derangements may also occur, typically in about 0.5%, are also seen at similar rates with placebo use and repeated enzyme testing, and generally return to normal either without discontinuance over time or after briefly discontinuing the drug. Multiple other side-effects occur rarely; typically also at similar rates with only placebo in the large statin safety/efficacy trials. A clearer major safety concern, myositis, myopathy, rarely with rhabdomyolysis (the pathological breakdown of skeletal muscle) may lead to acute renal failure when muscle breakdown products damage the kidney. Coenzyme Q10 (ubiquinone) levels are decreased in statin use; Q10 supplements are sometimes used to treat statin-associated myopathy, though evidence of their effectiveness is currently lacking. One 2004 study found that of 10,000 patients treated for one year, 0.44 will develop rhabdomyolysis. Cerivastatin, which was withdrawn by its manufacturer for this reason in 2001, had a much higher incidence (more than 10x). All commonly used statins show somewhat similar results, however the newer statins, characterized by longer pharmacological half-lives and more cellular specificity, have had a better ratio of efficacy to lower adverse effect rates. The risk of myopathy is lowest with pravastatin and fluvastatin probably because they are more hydrophillic and as a result have less muscle penetration. Despite initial concerns that statins might increase the risk of cancer, various studies concluded later that statins have no influence on cancer risk (including the heart protection study and a 2006 meta-analysis). Indeed, a 2005 trial showed that patients taking statins for over 5 years reduced their risk of colorectal cancer by 50%; this effect was not exhibited by fibrates. The trialists warn that the number needed to treat would approximate 5000, making statins unlikely tools for primary prevention. ## Drug interactions Combining any statin with a fibrate, another category of lipid-lowering drugs, increases the risks for rhabdomyolysis to almost 6.0 per 10,000 person-years. Most physicians have now abandoned routine monitoring of liver enzymes and creatine kinase, although they still consider this prudent in those on high-dose statins or in those on statin/fibrate combinations, and mandatory in the case of muscle cramps or of deterioration in renal function. Consumption of grapefruit or grapefruit juice inhibits the metabolism of statins—furanocoumarins in grapefruit juice inhibit the cytochrome P450 enzyme CYP3A4, which is involved in the metabolism of most statins (however it is a major inhibitor of only atorvastatin, lovastatin and simvastatin) and some other medications (it had been thought that flavonoids were responsible). This increases the levels of the statin, increasing the risk of dose-related adverse effects (including myopathy/rhabdomyolysis). Consequently, consumption of grapefruit juice is not recommended in patients undergoing therapy with most statins. An alternative, somewhat risky, approach is that some users take grapefruit juice to enhance the effect of lower (hence cheaper) doses of statins. This is not recommended as a result of the increased risk and potential for statin toxicity. # Pharmacogenomics A 2004 study showed that patients with one of two common single nucleotide polymorphisms (small genetic variations) in the HMG-CoA reductase gene were less responsive to statins. # Mode of action ## Cholesterol lowering Most circulating cholesterol is manufactured internally, in amounts of about 1000 mg/day, via steroid biosynthesis through the HMG-CoA reductase pathway. Cholesterol, both from dietary intake and secreted into the duodenum as bile from the liver, is typically absorbed at a rate of 50% by the small intestines. The typical diet in the United States and many other Western countries is estimated as adding about 200–300 mg/day to intestinal intake, an amount much smaller than that secreted into the intestine in the bile. Thus internal production is an important factor. Cholesterol is not water-soluble, and is therefore carried in the blood in the form of lipoproteins, the type being determined by the apoprotein, a protein coating that acts as an emulsifier. The relative balance between these lipoproteins is determined by various factors, including genetics, diet, and insulin resistance. Low density lipoprotein (LDL) and very low density lipoprotein (VLDL) carry cholesterol toward tissues, and elevated levels of these lipoproteins are associated with atheroma formation (fat-containing deposits in the arterial wall) and cardiovascular disease. High density lipoprotein, in contrast, carries cholesterol back to the liver and is associated with protection against cardiovascular disease. Statins act by competitively inhibiting HMG-CoA reductase, the first committed enzyme of the HMG-CoA reductase pathway. By reducing intracellular cholesterol levels, they cause liver cells to make more LDL receptors, leading to increased clearance of low-density lipoprotein from the bloodstream. Direct evidence of the action of statin-based cholesterol lowering on atherosclerosis was presented in the ASTEROID trial, which demonstrated regression of atheroma employing intravascular ultrasound. ## Non-cholesterol related actions Statins exhibit action beyond lipid-lowering activity in the prevention of atherosclerosis. Researchers hypothesize that statins prevent cardiovascular disease via four proposed mechanisms (all subjects of a large body of biomedical research): - Improving endothelial function - Modulate inflammatory responses - Maintain plaque stability - Prevent thrombus formation # Controversy Some scientists take a skeptical view of the need for many people to require statin treatment. The International Network of Cholesterol Skeptics is a group that has questioned the "lipid hypothesis" that supports cholesterol lowering as a preventive measure for heart disease, and has argued that statins - especially at higher doses - may not be as beneficial or safe as suggested. Similarly, some authors argue that recommendations for the expanded use of statins to stave off cardiovascular disease are not supported by evidence.	Statins Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] # For patient information, click here The statins (or HMG-CoA reductase inhibitors) form a class of hypolipidemic drugs used to lower cholesterol levels in people with or at risk of cardiovascular disease. They lower cholesterol by inhibiting the enzyme HMG-CoA reductase, which is the rate-limiting enzyme of the mevalonate pathway of cholesterol synthesis. Inhibition of this enzyme in the liver stimulates LDL receptors, resulting in an increased clearance of low-density lipoprotein (LDL) from the bloodstream and a decrease in blood cholesterol levels. The first results can be seen after one week of use and the effect is maximal after four to six weeks. # History Template:Seealso Akira Endo and Masao Kuroda of Tokyo, Japan commenced research into inhibitors of HMG-CoA reductase in 1971 (Endo 1992). This team reasoned that certain microorganisms may produce inhibitors of the enzyme to defend themselves against other organisms, as mevalonate is a precursor of many substances required by organisms for the maintenance of their cell wall (ergosterol) or cytoskeleton (isoprenoids).[1] The first agent isolated was mevastatin (ML-236B), a molecule produced by Penicillium citrinum. The pharmaceutical company Merck & Co. showed an interest in the Japanese research in 1976, and isolated lovastatin (mevinolin, MK803), the first commercially marketed statin, from the mold Aspergillus terreus. Dr Endo was awarded the 2006 Japan Prize for his work on the development of statins. # Indications and uses Statins, the most potent cholesterol-lowering agents available, lower LDL cholesterol (so-called "bad cholesterol") by 30–50%.[2] However, they have less effect than the fibrates or niacin in reducing triglycerides and raising HDL-cholesterol ("good cholesterol"). Professional guidelines generally require that the patient has tried a cholesterol-lowering diet before statin use is considered; statins or other pharmacologic agents may then be recommended for patients who do not meet their lipid-lowering goals through diet and lifestyle approaches. The indications for the prescription of statins have broadened over the years. Initial studies, such as the Scandinavian Simvastatin Survival Study (4S), supported the use of statins in secondary prevention for cardiovascular disease, or as primary prevention only when the risk for cardiovascular disease was significantly raised (as indicated by the Framingham risk score).[3] Indications were broadened considerably by studies such as the Heart Protection Study (HPS), which showed preventative effects of statin use in specific risk groups, such as diabetics. The ASTEROID trial, published in 2006, using only a statin at high dose, achieved lower than usual target calculated LDL values and showed disease regression within the coronary arteries using intravascular ultrasonography.[4] Based on clinical trials, the National Cholesterol Education Program guidelines, and the increasing focus on aggressively lowering LDL-cholesterol, the statins continue to play an important role in both the primary and secondary prevention of coronary heart disease, myocardial infarction, stroke and peripheral artery disease. Research continues into other areas where statins also appear to have a favorable effect: inflammation, dementia,[5] cancer,[6] nuclear cataracts,[7] and pulmonary hypertension.[citation needed] # Members The statins are divided into two groups: fermentation-derived and synthetic. The statins include, in alphabetical order (brand names vary in different countries): LDL-lowering potency varies between agents. Cerivastatin is the most potent, followed by (in order of decreasing potency) rosuvastatin, atorvastatin, simvastatin, lovastatin, pravastatin, and fluvastatin.[8] The relative potency of pitavastatin has not yet been fully established. ## Comparative effectiveness No large scale comparison exists that examines the effectiveness of the various statins against one another. An independent analysis has been done to compare atorvastatin, pravastatin and simvastatin, based on their effectiveness against placebos. It found that, at commonly prescribed doses, there are no statistically significant differences in reducing cardiovascular morbidity and mortality.[9] # Safety ## Adverse effects While some patients on statin therapy report myalgias, muscle cramps, or far less-frequent gastrointestinal or other symptoms, similar symptoms are also reported with placebo use in all the large statin safety/efficacy trials and usually resolve, either on their own or on temporarily lowering/stopping the dose. Liver enzyme derangements may also occur, typically in about 0.5%,[citation needed] are also seen at similar rates with placebo use and repeated enzyme testing, and generally return to normal either without discontinuance over time or after briefly discontinuing the drug. Multiple other side-effects occur rarely; typically also at similar rates with only placebo in the large statin safety/efficacy trials. A clearer major safety concern, myositis, myopathy, rarely with rhabdomyolysis (the pathological breakdown of skeletal muscle) may lead to acute renal failure when muscle breakdown products damage the kidney. Coenzyme Q10 (ubiquinone) levels are decreased in statin use;[10] Q10 supplements are sometimes used to treat statin-associated myopathy, though evidence of their effectiveness is currently lacking.[11] One 2004 study found that of 10,000 patients treated for one year, 0.44 will develop rhabdomyolysis. Cerivastatin, which was withdrawn by its manufacturer for this reason in 2001, had a much higher incidence (more than 10x).[12] All commonly used statins show somewhat similar results, however the newer statins, characterized by longer pharmacological half-lives and more cellular specificity, have had a better ratio of efficacy to lower adverse effect rates. The risk of myopathy is lowest with pravastatin and fluvastatin probably because they are more hydrophillic and as a result have less muscle penetration. Despite initial concerns that statins might increase the risk of cancer, various studies concluded later that statins have no influence on cancer risk (including the heart protection study and a 2006 meta-analysis[13]). Indeed, a 2005 trial showed that patients taking statins for over 5 years reduced their risk of colorectal cancer by 50%; this effect was not exhibited by fibrates. The trialists warn that the number needed to treat would approximate 5000, making statins unlikely tools for primary prevention.[14] ## Drug interactions Combining any statin with a fibrate, another category of lipid-lowering drugs, increases the risks for rhabdomyolysis to almost 6.0 per 10,000 person-years.[12] Most physicians have now abandoned routine monitoring of liver enzymes and creatine kinase, although they still consider this prudent in those on high-dose statins or in those on statin/fibrate combinations, and mandatory in the case of muscle cramps or of deterioration in renal function. Consumption of grapefruit or grapefruit juice inhibits the metabolism of statins—furanocoumarins in grapefruit juice inhibit the cytochrome P450 enzyme CYP3A4, which is involved in the metabolism of most statins (however it is a major inhibitor of only atorvastatin, lovastatin and simvastatin) and some other medications[15] (it had been thought that flavonoids were responsible). This increases the levels of the statin, increasing the risk of dose-related adverse effects (including myopathy/rhabdomyolysis). Consequently, consumption of grapefruit juice is not recommended in patients undergoing therapy with most statins. An alternative, somewhat risky, approach is that some users take grapefruit juice to enhance the effect of lower (hence cheaper) doses of statins. This is not recommended as a result of the increased risk and potential for statin toxicity. # Pharmacogenomics A 2004 study showed that patients with one of two common single nucleotide polymorphisms (small genetic variations) in the HMG-CoA reductase gene were less responsive to statins.[16] # Mode of action ## Cholesterol lowering Most circulating cholesterol is manufactured internally, in amounts of about 1000 mg/day, via steroid biosynthesis through the HMG-CoA reductase pathway. Cholesterol, both from dietary intake and secreted into the duodenum as bile from the liver, is typically absorbed at a rate of 50% by the small intestines. The typical diet in the United States and many other Western countries is estimated as adding about 200–300 mg/day to intestinal intake, an amount much smaller than that secreted into the intestine in the bile. Thus internal production is an important factor. Cholesterol is not water-soluble, and is therefore carried in the blood in the form of lipoproteins, the type being determined by the apoprotein, a protein coating that acts as an emulsifier. The relative balance between these lipoproteins is determined by various factors, including genetics, diet, and insulin resistance. Low density lipoprotein (LDL) and very low density lipoprotein (VLDL) carry cholesterol toward tissues, and elevated levels of these lipoproteins are associated with atheroma formation (fat-containing deposits in the arterial wall) and cardiovascular disease. High density lipoprotein, in contrast, carries cholesterol back to the liver and is associated with protection against cardiovascular disease. Statins act by competitively inhibiting HMG-CoA reductase, the first committed enzyme of the HMG-CoA reductase pathway. By reducing intracellular cholesterol levels, they cause liver cells to make more LDL receptors, leading to increased clearance of low-density lipoprotein from the bloodstream.[17] Direct evidence of the action of statin-based cholesterol lowering on atherosclerosis was presented in the ASTEROID trial, which demonstrated regression of atheroma employing intravascular ultrasound.[4] ## Non-cholesterol related actions Statins exhibit action beyond lipid-lowering activity in the prevention of atherosclerosis. Researchers hypothesize that statins prevent cardiovascular disease via four proposed mechanisms (all subjects of a large body of biomedical research):[18] - Improving endothelial function - Modulate inflammatory responses - Maintain plaque stability - Prevent thrombus formation # Controversy Some scientists take a skeptical view of the need for many people to require statin treatment. The International Network of Cholesterol Skeptics is a group that has questioned the "lipid hypothesis" that supports cholesterol lowering as a preventive measure for heart disease, and has argued that statins - especially at higher doses - may not be as beneficial or safe as suggested.[19] Similarly, some authors argue that recommendations for the expanded use of statins to stave off cardiovascular disease are not supported by evidence.[20]	https://www.wikidoc.org/index.php/HMG_coenzyme-A_reductase_inhibitor
a33dc1a682fbd0b341ac46b9b9a56a2a269283b8	wikidoc	HORMAD1	HORMAD1 HORMA domain-containing protein 1 (HORMAD1) also known as cancer/testis antigen 46 (CT46) is a protein that in humans is encoded by the HORMAD1 gene. # Function HORMAD1 plays a key role in meiotic progression. Regulates 3 different functions during meiosis. It: - ensures that sufficient numbers of processed DNA double-strand breaks (DSBs) are available for successful homology search by increasing the steady-state numbers of single-stranded DSB ends. - promotes synaptonemal-complex formation independently of its role in homology search. - plays a key role in the male mid-pachytene checkpoint and the female meiotic prophase checkpoint: required for efficient build-up of ATR activity on unsynapsed chromosome regions, a process believed to form the basis of meiotic silencing of unsynapsed chromatin (MSUC) and meiotic prophase quality control in both sexes (By similarity)	HORMAD1 HORMA domain-containing protein 1 (HORMAD1) also known as cancer/testis antigen 46 (CT46) is a protein that in humans is encoded by the HORMAD1 gene.[1][2][3] # Function HORMAD1 plays a key role in meiotic progression. Regulates 3 different functions during meiosis. It: - ensures that sufficient numbers of processed DNA double-strand breaks (DSBs) are available for successful homology search by increasing the steady-state numbers of single-stranded DSB ends. - promotes synaptonemal-complex formation independently of its role in homology search. - plays a key role in the male mid-pachytene checkpoint and the female meiotic prophase checkpoint: required for efficient build-up of ATR activity on unsynapsed chromosome regions, a process believed to form the basis of meiotic silencing of unsynapsed chromatin (MSUC) and meiotic prophase quality control in both sexes (By similarity)	https://www.wikidoc.org/index.php/HORMAD1
ccf625f66d7f8264823f7efad3daa52908e90891	wikidoc	HRASLS3	HRASLS3 Group XVI phospholipase A2 also commonly known as adipocyte phospholipase A2 (AdPLA) is an enzyme that in humans is encoded by the PLA2G16 gene. This enzyme has also been identified as PLA2G16, HRASLS3, HREV107, HREV107-3, MGC118754 or H-REV107-1 from studies on class II tumor suppression but not on its enzymatic properties. AdPLA is encoded by a 1.3 kilobase AdPLA messenger RNA and is an 18 kDa protein. It belongs to a superfamily of phospholipase A2 (PLA2) enzymes and is found primarily in adipose tissue. AdPLA regulates adipocyte lipolysis and release of fatty acids through a G-protein coupled pathway involving prostaglandin and EP3. It has also been reported to play a crucial role in the development of obesity in mouse models. # Enzyme characteristics AdPLA has been characterized in Group XVI as a separate subgroup of the PLA2 family for its distinct properties from other known PLA2s. It bears similarity to its PLA2 family in phospholipase activity and calcium dependence. Unlike other PLA2 enzymes, AdPLA is expressed predominantly in adipose tissue at higher levels than in the rest of the body, more so in white adipose tissue (WAT) than brown adipose tissue (BAT). Its primary enzymatic function is to catalyze the preferential hydrolysis of phosphatidylcholines at the sn-2 position, generating free fatty acids. AdPLA contains a membrane-spanning domain on the C-terminus, which localizes intracellularly for phospholipase activity in proximity to cyclooxygenase 1 (COX-1). His-23 and Cys-113 residues have been shown to be essential in AdPLA activity, which differs from the known His/Asp catalytic dyad or Ser/His/Asp catalytic triad of other PLA2 enzymes. Gln-129 and Asn-112 have also been shown to be necessary in catalysis but their role is not known. AdPLA activity is calcium and pH dependent. Calcium binds to AdPLA and forms a positively charged oxyanion hole to stabilize a negatively charged transition state, similar to other PLA2 active sites. Whereas asparagine binds to calcium in other PLA2 enzymes, the residue that participates in the creation of oxyanion hole in AdPLA has not yet been verified. Optimum AdPLA activity occurs in relatively basic conditions, between pH 7 and 9, to facilitate formation of a histidine-water complex and subsequent fatty acid hydrolysis. # Function Studies on AdPLA have shown lipolysis regulation following a G-protein coupled pathway in WAT. WAT is responsible for releasing fatty acids from stored triacylglycerol as energy sources for other tissues which is regulated predominately by AdPLA over other phospholipase A2 enzymes. Lipolysis is inversely related to AdPLA activity. AdPLA catalyzes the rate-limiting step, production of arachidonic acid, for the production of prostaglandins, specifically prostaglandin E2 (PGE2). PGE2 enters the signaling pathway binding to G protein-coupled receptor (EP3) which inhibits adenylyl cyclase. Inhibition of adenylyl cyclase decreases the conversion of cyclic AMP (cAMP) from ATP. Lower levels of cAMP decrease the activity of protein kinase A to phosphorylate, thereby activating, hormone-sensitive lipase. The opposite effect can be reached with inactivated AdPLA, decreasing PGE2 concentration and EP3 activity, leading to an increase in cAMP and lipase activity. This mechanism was postulated on the basis that the predominant signaling protein and receptor present in WAT are PGE2 and EP3. These results were based on a mouse model and although they are mammalian cells, it has not been shown to apply to human cells. # Effects on obesity Obesity has been attributed to adipocyte hypertrophy, where triacylglycerol synthesis exceeds lipolysis, resulting in elevated triacylglycerol storage. Previous studies have associated obesity with endocrine factors and have led pharmacological work toward hormone regulation. Studies on AdPLA deficient mice have shown that the enzyme increased lipolysis in WAT as a result of decreased lipolysis regulation. AdPLA deficiency was shown to reduce adipose tissue mass for mice in both standard and high fat diets. Adipocyte hypotrophy was attributed primarily to reduced triacylglyceride content in WAT from lipolysis, while adipocyte differentiation did not play a role in reduced adipose tissue despite the effects of prostaglandins on adipogenesis. AdPLA defieciency also led to higher oxygen consumption due to the upreguation of genes involved in oxidative metabolism, increasing fatty acid oxidation. One upregulated gene in particular, uncoupling protein-1 (UCP1), has been shown to reduce diet-induced obesity. Studies on AdPLA deficient and genetically obese mice (leptin deficiency) have also shown similar effects, reduced adipose tissue mass and increased lipolysis by reduction in PGE2 and EP3 activity. Fatty acid oxidation was also found to increase to levels of wild-type mice that were deficient in non-AdPLA deficient obese mice. Body composition also showed a higher percentage of water and lean tissue mass compared to non-AdPLA deficient obese mice. AdPLA deficiency also demonstrated adverse effects, increasing ectopic triglyceride storage and insulin resistance. Liver enlargement was attributed to higher fatty acid uptake and triacylglycerol content. Insulin stimulated glucose uptake and metabolism were also blunted in AdPLA deficiency, decreasing glycolysis and glycogen synthesis. Despite these side effects, AdPLA is a novel breakthrough in studying autocrine and paracrine action of AdPLA in regulating obesity and fat metabolism. These side effects have triggered new studies to be performed on reduction of AdPLA function as opposed to complete ablation.	HRASLS3 Group XVI phospholipase A2 also commonly known as adipocyte phospholipase A2 (AdPLA) is an enzyme that in humans is encoded by the PLA2G16 gene.[1][2][3] This enzyme has also been identified as PLA2G16, HRASLS3, HREV107, HREV107-3, MGC118754 or H-REV107-1 from studies on class II tumor suppression but not on its enzymatic properties.[4] AdPLA is encoded by a 1.3 kilobase AdPLA messenger RNA and is an 18 kDa protein. It belongs to a superfamily of phospholipase A2 (PLA2) enzymes and is found primarily in adipose tissue. AdPLA regulates adipocyte lipolysis and release of fatty acids through a G-protein coupled pathway involving prostaglandin and EP3. It has also been reported to play a crucial role in the development of obesity in mouse models.[5] # Enzyme characteristics AdPLA has been characterized in Group XVI as a separate subgroup of the PLA2 family for its distinct properties from other known PLA2s. It bears similarity to its PLA2 family in phospholipase activity and calcium dependence. Unlike other PLA2 enzymes, AdPLA is expressed predominantly in adipose tissue at higher levels than in the rest of the body, more so in white adipose tissue (WAT) than brown adipose tissue (BAT). Its primary enzymatic function is to catalyze the preferential hydrolysis of phosphatidylcholines at the sn-2 position, generating free fatty acids. AdPLA contains a membrane-spanning domain on the C-terminus, which localizes intracellularly for phospholipase activity in proximity to cyclooxygenase 1 (COX-1). His-23 and Cys-113 residues have been shown to be essential in AdPLA activity, which differs from the known His/Asp catalytic dyad or Ser/His/Asp catalytic triad of other PLA2 enzymes. Gln-129 and Asn-112 have also been shown to be necessary in catalysis but their role is not known.[2] AdPLA activity is calcium and pH dependent. Calcium binds to AdPLA and forms a positively charged oxyanion hole to stabilize a negatively charged transition state, similar to other PLA2 active sites. Whereas asparagine binds to calcium in other PLA2 enzymes,[6] the residue that participates in the creation of oxyanion hole in AdPLA has not yet been verified. Optimum AdPLA activity occurs in relatively basic conditions, between pH 7 and 9, to facilitate formation of a histidine-water complex and subsequent fatty acid hydrolysis.[2] # Function Studies on AdPLA have shown lipolysis regulation following a G-protein coupled pathway in WAT.[5] WAT is responsible for releasing fatty acids from stored triacylglycerol as energy sources for other tissues which is regulated predominately by AdPLA over other phospholipase A2 enzymes. Lipolysis is inversely related to AdPLA activity. AdPLA catalyzes the rate-limiting step, production of arachidonic acid, for the production of prostaglandins, specifically prostaglandin E2 (PGE2). PGE2 enters the signaling pathway binding to G protein-coupled receptor (EP3) which inhibits adenylyl cyclase. Inhibition of adenylyl cyclase decreases the conversion of cyclic AMP (cAMP) from ATP. Lower levels of cAMP decrease the activity of protein kinase A to phosphorylate, thereby activating, hormone-sensitive lipase.[7] The opposite effect can be reached with inactivated AdPLA, decreasing PGE2 concentration and EP3 activity, leading to an increase in cAMP and lipase activity. This mechanism was postulated on the basis that the predominant signaling protein and receptor present in WAT are PGE2 and EP3. These results were based on a mouse model and although they are mammalian cells, it has not been shown to apply to human cells. # Effects on obesity Obesity has been attributed to adipocyte hypertrophy, where triacylglycerol synthesis exceeds lipolysis, resulting in elevated triacylglycerol storage.[8] Previous studies have associated obesity with endocrine factors and have led pharmacological work toward hormone regulation.[9] Studies on AdPLA deficient mice have shown that the enzyme increased lipolysis in WAT as a result of decreased lipolysis regulation. AdPLA deficiency was shown to reduce adipose tissue mass for mice in both standard and high fat diets. Adipocyte hypotrophy was attributed primarily to reduced triacylglyceride content in WAT from lipolysis, while adipocyte differentiation did not play a role in reduced adipose tissue despite the effects of prostaglandins on adipogenesis.[10] AdPLA defieciency also led to higher oxygen consumption due to the upreguation of genes involved in oxidative metabolism, increasing fatty acid oxidation. One upregulated gene in particular, uncoupling protein-1 (UCP1), has been shown to reduce diet-induced obesity.[11] Studies on AdPLA deficient and genetically obese mice (leptin deficiency) have also shown similar effects, reduced adipose tissue mass and increased lipolysis by reduction in PGE2 and EP3 activity. Fatty acid oxidation was also found to increase to levels of wild-type mice that were deficient in non-AdPLA deficient obese mice. Body composition also showed a higher percentage of water and lean tissue mass compared to non-AdPLA deficient obese mice.[5] AdPLA deficiency also demonstrated adverse effects, increasing ectopic triglyceride storage and insulin resistance. Liver enlargement was attributed to higher fatty acid uptake and triacylglycerol content. Insulin stimulated glucose uptake and metabolism were also blunted in AdPLA deficiency, decreasing glycolysis and glycogen synthesis.[5] Despite these side effects, AdPLA is a novel breakthrough in studying autocrine and paracrine action of AdPLA in regulating obesity and fat metabolism. These side effects have triggered new studies to be performed on reduction of AdPLA function as opposed to complete ablation.[12]	https://www.wikidoc.org/index.php/HRASLS3
fb1c3717e08652c4a3bda3d1c0f6fb5485af5c78	wikidoc	HSD17B1	HSD17B1 17β-Hydroxysteroid dehydrogenase 1 (17β-HSD1) is an enzyme that in humans is encoded by the HSD17B1 gene. This enzyme oxidizes or reduces the C17 hydroxy/keto group of androgens and estrogens and hence is able to regulate the potency of these sex steroids # Function This enzyme is responsible for the interconversion of estrone (E1) and estradiol (E2) and for the interconversion of androstenedione and testosterone: The human 17β-HSD1 isozyme is highly specific for estrogens over androgens whereas the rodent isozyme is less specific. # Discovery Human 17β-HSD1 was the first enzyme of the 17β-HSD family to be cloned and to have its sequence identified. Its three-dimensional structure is also the first example of any human steroid-converting enzyme. # Structure This enzyme contains a short-chain dehydrogenase domain that contains a characteristic 3-layer (αβα) sandwich known as a Rossmann fold. The human enzyme contains 327 amino acids and exists as a homodimer with two identical subunits of 34.5 kDa The N-terminal short-chain dehydrogenase domain contains binding site for the NADP+/NADPH cofactor. A narrow, hydrophobic C-terminal domain contains a binding pocket for the steroid substrate. # Clinical significance Estradiol stimulates while dihydrotestosterone (DHT) inhibits breast cancer growth. Furthermore 17β-HSD1 levels positively correlate with estradiol and negatively correlate with DHT levels in breast cancer cells. Hence 17β-HSD1 represents a possible drug target for breast cancer treatment.	HSD17B1 17β-Hydroxysteroid dehydrogenase 1 (17β-HSD1) is an enzyme that in humans is encoded by the HSD17B1 gene.[1][2][3] This enzyme oxidizes or reduces the C17 hydroxy/keto group of androgens and estrogens and hence is able to regulate the potency of these sex steroids # Function This enzyme is responsible for the interconversion of estrone (E1) and estradiol (E2) and for the interconversion of androstenedione and testosterone: The human 17β-HSD1 isozyme is highly specific for estrogens over androgens whereas the rodent isozyme is less specific.[4] # Discovery Human 17β-HSD1 was the first enzyme of the 17β-HSD family to be cloned and to have its sequence identified.[5][6] Its three-dimensional structure is also the first example of any human steroid-converting enzyme.[7] # Structure This enzyme contains a short-chain dehydrogenase domain that contains a characteristic 3-layer (αβα) sandwich known as a Rossmann fold. The human enzyme contains 327 amino acids and exists as a homodimer with two identical subunits of 34.5 kDa [6][8] The N-terminal short-chain dehydrogenase domain contains binding site for the NADP+/NADPH cofactor. A narrow, hydrophobic C-terminal domain contains a binding pocket for the steroid substrate. # Clinical significance Estradiol stimulates while dihydrotestosterone (DHT) inhibits breast cancer growth. Furthermore 17β-HSD1 levels positively correlate with estradiol and negatively correlate with DHT levels in breast cancer cells. Hence 17β-HSD1 represents a possible drug target for breast cancer treatment.[9]	https://www.wikidoc.org/index.php/HSD17B1
1fab5eef597b25ba0e2ea0a300b5623f37a1b544	wikidoc	HSD17B2	HSD17B2 17β-Hydroxysteroid dehydrogenase 2 (17β-HSD2) is an enzyme of the 17β-hydroxysteroid dehydrogenase (17β-HSD) family that in humans is encoded by the HSD17B2 gene. # Function 17β-HSD2 is involved in inactivation of androgens and estrogens, being accurately describable as "antiandrogenic" and "antiestrogenic", and is the key 17β-HSD isozyme in androgen and estrogen inactivation. Specific reactions catalyzed by 17β-HSD2 include estradiol to estrone, testosterone to androstenedione, and androstenediol to DHEA. In addition to 17β-HSD activity, this enzyme also shows high 20α-hydroxysteroid dehydrogenase activity and can activate the weak progestogen 20α-hydroxyprogesterone into the potent progestogen progesterone. # Expression 17β-HSD2 is widely expressed throughout the body including in the placenta, liver, intestines, endometrium, kidney, pancreas, breast, prostate, bone, and many other tissues. # Clinical significance Polymorphisms in HSD17B2 have been associated with breast cancer and prostate cancer. 17β-HSD2 activity has also been associated with endometriosis and osteoporosis, and inhibitors of the enzyme are of potential interest in the treatment of the latter condition. Inactivating mutations resulting in a syndrome of congenital deficiency of 17β-HSD2 have not been reported to date.	HSD17B2 17β-Hydroxysteroid dehydrogenase 2 (17β-HSD2) is an enzyme of the 17β-hydroxysteroid dehydrogenase (17β-HSD) family that in humans is encoded by the HSD17B2 gene.[1][2][3] # Function 17β-HSD2 is involved in inactivation of androgens and estrogens,[4] being accurately describable as "antiandrogenic" and "antiestrogenic",[5] and is the key 17β-HSD isozyme in androgen and estrogen inactivation.[4][additional citation(s) needed] Specific reactions catalyzed by 17β-HSD2 include estradiol to estrone, testosterone to androstenedione, and androstenediol to DHEA.[4][6] In addition to 17β-HSD activity, this enzyme also shows high 20α-hydroxysteroid dehydrogenase activity and can activate the weak progestogen 20α-hydroxyprogesterone into the potent progestogen progesterone.[4][6] # Expression 17β-HSD2 is widely expressed throughout the body including in the placenta, liver, intestines, endometrium, kidney, pancreas, breast, prostate, bone, and many other tissues.[7][8] # Clinical significance Polymorphisms in HSD17B2 have been associated with breast cancer and prostate cancer.[9] 17β-HSD2 activity has also been associated with endometriosis and osteoporosis,[10] and inhibitors of the enzyme are of potential interest in the treatment of the latter condition.[11][12] Inactivating mutations resulting in a syndrome of congenital deficiency of 17β-HSD2 have not been reported to date.[13]	https://www.wikidoc.org/index.php/HSD17B2
2eb6e9b6d793322891da4e1bb5c9e704d54ce28a	wikidoc	HSD17B4	HSD17B4 D-bifunctional protein (DBP), also known as peroxisomal multifunctional enzyme type 2 (MFP-2), as well as 17β-hydroxysteroid dehydrogenase type IV (17β-HSD type IV) is a protein that in humans is encoded by the HSD17B4 gene. It's an alcohol oxidoreductase, specifically 17β-Hydroxysteroid dehydrogenase. It is involved in fatty acid β-oxidation and steroid metabolism (cf. steroidogenesis). # Function The HSD17B4 gene encodes an enzyme involved in peroxisomal fatty acid beta-oxidation. It was first identified as a 17-beta-estradiol dehydrogenase (Leenders et al., 1996; van Grunsven et al., 1998). Peroxisomal beta-oxidation of fatty acids, originally described by Lazarow and de Duve (1976), is catalyzed by 3 enzymes: acyl-CoA oxidase (see, e.g., ACOX1, MIM 609751); the 'D-bifunctional enzyme,' with enoyl-CoA hydratase and D-3-hydroxyacyl-CoA dehydrogenase activity, and 3-ketoacyl-CoA thiolase (MIM 604054). See also the L-bifunctional peroxisomal protein (EHHADH; MIM 607037). The D- and L-bifunctional proteins have different substrate specificities. The D-bifunctional protein catalyzes the formation of 3-ketoacyl-CoA intermediates from both straight-chain and 2-methyl-branched-chain fatty acids and also acts in shortening cholesterol for bile acid formation. In contrast, the L-specific bifunctional protein does not have the latter 2 activities (Jiang et al., 1997).	HSD17B4 D-bifunctional protein (DBP), also known as peroxisomal multifunctional enzyme type 2 (MFP-2), as well as 17β-hydroxysteroid dehydrogenase type IV (17β-HSD type IV) is a protein that in humans is encoded by the HSD17B4 gene.[1][2][3][4] It's an alcohol oxidoreductase, specifically 17β-Hydroxysteroid dehydrogenase. It is involved in fatty acid β-oxidation and steroid metabolism (cf. steroidogenesis).[4] # Function The HSD17B4 gene encodes an enzyme involved in peroxisomal fatty acid beta-oxidation. It was first identified as a 17-beta-estradiol dehydrogenase (Leenders et al., 1996; van Grunsven et al., 1998). Peroxisomal beta-oxidation of fatty acids, originally described by Lazarow and de Duve (1976), is catalyzed by 3 enzymes: acyl-CoA oxidase (see, e.g., ACOX1, MIM 609751); the 'D-bifunctional enzyme,' with enoyl-CoA hydratase and D-3-hydroxyacyl-CoA dehydrogenase activity, and 3-ketoacyl-CoA thiolase (MIM 604054). See also the L-bifunctional peroxisomal protein (EHHADH; MIM 607037). The D- and L-bifunctional proteins have different substrate specificities. The D-bifunctional protein catalyzes the formation of 3-ketoacyl-CoA intermediates from both straight-chain and 2-methyl-branched-chain fatty acids and also acts in shortening cholesterol for bile acid formation. In contrast, the L-specific bifunctional protein does not have the latter 2 activities (Jiang et al., 1997).[supplied by OMIM][3]	https://www.wikidoc.org/index.php/HSD17B4
dcc85398f79c0ed2349fbd998243e0460f1e5746	wikidoc	HSP90B1	HSP90B1 Heat shock protein 90kDa beta member 1 (HSP90B1), known also as endoplasmin, gp96, grp94, or ERp99, is a chaperone protein that in humans is encoded by the HSP90B1 gene. HSP90B1 is an HSP90 paralogue that is found in the endoplasmic reticulum. It plays critical roles in folding proteins in the secretory pathway such as Toll-like receptors and integrins. It has been implicated as an essential immune chaperone to regulate both innate and adaptive immunity. Tumor-derived HSP90B1 (vitespen) has entered clinical trials for cancer immunotherapy. grp94 has been shown to be a target for treatment of a plethora of diseases such as glaucoma, multiple myeloma , and metastatic cancer. grp94 includes 5 distinct amino acids in its primary sequence which creates 2 unique sub-pockets, S1 and S2. These sub-pockets have been utilized in current research in order to inhibit the chaperone since its client proteins seem to be up-regulated in cancer cells.	HSP90B1 Heat shock protein 90kDa beta member 1 (HSP90B1), known also as endoplasmin, gp96, grp94, or ERp99, is a chaperone protein that in humans is encoded by the HSP90B1 gene.[1][2] HSP90B1 is an HSP90 paralogue that is found in the endoplasmic reticulum. It plays critical roles in folding proteins in the secretory pathway such as Toll-like receptors and integrins.[3][4] It has been implicated as an essential immune chaperone to regulate both innate and adaptive immunity.[5] Tumor-derived HSP90B1 (vitespen) has entered clinical trials for cancer immunotherapy.[6][7][8][9] grp94 has been shown to be a target for treatment of a plethora of diseases such as glaucoma, multiple myeloma , and metastatic cancer. grp94 includes 5 distinct amino acids in its primary sequence which creates 2 unique sub-pockets, S1 and S2. These sub-pockets have been utilized in current research in order to inhibit the chaperone since its client proteins seem to be up-regulated in cancer cells. [10]	https://www.wikidoc.org/index.php/HSP90B1
4b7df19ad584602b11ee937e5963da5b9141b25b	wikidoc	RPS6KA1	RPS6KA1 Lua error in Module:Redirect at line 65: could not parse redirect on page "HU-1". Ribosomal protein S6 kinase alpha-1 is an enzyme that in humans is encoded by the RPS6KA1 gene. # Function This gene encodes a member of the RSK (ribosomal S6 kinase) family of serine/threonine kinases. This kinase contains 2 nonidentical kinase catalytic domains and phosphorylates various substrates, including members of the mitogen-activated kinase (MAPK) signalling pathway. The activity of this protein has been implicated in controlling cell growth and differentiation. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. # Interactions RPS6KA1 has been shown to interact with: - IκBα, - MAPK1, - TOB1 - TSC2, and - YWHAB.	RPS6KA1 Lua error in Module:Redirect at line 65: could not parse redirect on page "HU-1". Ribosomal protein S6 kinase alpha-1 is an enzyme that in humans is encoded by the RPS6KA1 gene.[1] # Function This gene encodes a member of the RSK (ribosomal S6 kinase) family of serine/threonine kinases. This kinase contains 2 nonidentical kinase catalytic domains and phosphorylates various substrates, including members of the mitogen-activated kinase (MAPK) signalling pathway. The activity of this protein has been implicated in controlling cell growth and differentiation. Alternate transcriptional splice variants, encoding different isoforms, have been characterized.[2] # Interactions RPS6KA1 has been shown to interact with: - IκBα,[3] - MAPK1,[4][5][6] - TOB1[7] - TSC2,[8][9] and - YWHAB.[10]	https://www.wikidoc.org/index.php/HU-1
3c1e869dd2e907f1f9df7bf27e400ee250c66312	wikidoc	Hadacol	Hadacol Hadacol was a patent medicine marketed as a vitamin supplement. Its principal attraction, however, was that it contained 12 percent alcohol (listed on the tonic bottle's label as a "preservative"), which made it quite popular in the dry counties of the southern United States. It was the product of four-term Louisiana state Senator Dudley J. LeBlanc (1894-1971), a Democrat from Abbeville in Vermilion Parish. He was not a medical doctor, nor a registered pharmacist, but had a strong talent for self-promotion. Time Magazine once described him as "...a stem-winding salesman who knows every razzle-dazzle switch in the pitchman's trade". # Origins LeBlanc conceived the idea that became "Hadacol" in New Orleans, when he injured a foot. He asked a doctor to give him medication for pain: then he found that what the doctor gave him was a B-vitamin elixir, which he proposed to duplicate with a few changes and market it to a mass consumer market (Years later, reports arose that LeBlanc offered the doctor a share of the business, who refused. On a return visit, LeBlanc allegedly stole a bottle of the medicine when the nurse had left the room). LeBlanc said that his research showed that multivitamins taken collectively would yield greater results than a single vitamin for a specific problem. # Dosage The label on the tonic's bottle clearly stated that the recommended dosage (1 tablespoonful taken 4 times a day) was to be taken "...in a 1/2 glass of water after meals and before retiring". However, some pharmacies in dry counties were known to sell it by the shot-glass. In Northbrook, Illinois, a suburb of Chicago, sales of Hadacol were limited to liquor stores. One of the tonic's unusual ingredients, "Diluted Acid Hydrochloric", is what is known as a "hydrochloric wash": a heavily diluted form of the acid that opens the arteries and allows the body's quicker absorption of the other ingredients, including the 12 percent alcohol "preservative". # Promotion LeBlanc created the name "Hadacol" from his former business, the Happy Day Company, maker of Happy Day Headache Powders (which had been seized by the FDA) and Dixie Dew Cough Syrup. "Happy" became "HA", "Days" became "DA," "Company" became "CO", and his own last name "LeBlanc" provided the "L". Hence the created named was "Hadacol." However, when LeBlanc was asked about the name, he would often joke, "Well, I hadda' call (Hadacol) it something!" A two-page advertisement for Hadacol appeared in the centerfold of the 1951 edition of Grier's Almanac, an annual publication marketed to farmers in the Southern USA. The ad's headline read (in very large type): - Don't Be Satisfied With Symptomatic Relief! It's Possible to RELIEVE THE CAUSE OF YOUR AILMENTS When Lack Of Vitamins B1, B2, Iron and Niacin Cause Stomach Disturbances, Gas, Heartburn, Indigestion, Nagging Aches and Pains, and Certain Nervous Disorders. The ad continued with testimonials and a glowing plug for Senator LeBlanc, stressing the curative powers of Hadacol for a number of ailments "...due to lack of Vitamins B1, B2, Iron and Niacin". LeBlanc promoted the tonic as a "Dietary Supplement" instead of a medicine, stating that it was "...formulated as an Aid to Nature in rebuilding the Pep, Strength and Energy of Buoyant Health when the System is deficient in the Vitamins and Minerals found in this Tonic..." The American Medical Association was not as appreciative. In an official press release in 1951, the AMA stated, "It is hoped that no doctor will be uncritical enough to join in the promotion of Hadacol. It is difficult to imagine how one could do himself or his profession greater harm from the standpoint of the abuse of the trust of a patient suffering from any condition. Hadacol is not a specific medication. It is not even a specific preventive measure." LeBlanc flooded the airwaves with testimonials to the powers of the seemingly miraculous (yet foul tasting) brown liquid and turned the jingle called "Hadacol Boogie" into a popular recording. Promotional items included various flyers, signs and clocks, a "Captain Hadacol" comic book, an almanac, plastic thimbles printed with the Hadacol logo, glasses used for taking the diluted mixture, and a stamped metal token redeemable for 25 cents towards the purchase of any bottle of Hadacol (LeBlanc brazenly placed his own portrait on the front of the token, and the trademarked logo on the back). These items, along with the Hadacol bottles and the boxes they were packaged in, are now much sought-after items, and fetch high prices among collectors of Southern memorabilia and medical quackery. In 1950, LeBlanc offered a handsome financial incentive to anyone who could provide him with a parrot that was trained to say "Polly wants Hadacol!" The parrot was to be exhibited at promotions. The offer included the following: - The owner of such a bird, if selected, will be given a reasonable compensation on a contract basis. The owner and the parrot will travel in a limousine with the parrot's name engraved in gold on the door and will stay only at the best hotels. The parrot will be furnished a gold cage and its life insured. The parrot will visit large drugstores, perform at conventions, etc., and may be presented on radio and television. The Le Blanc Corporation has a triple A high credit rating. # The Hadacol Caravan LeBlanc was an entrepreneur in other areas too, but it is Hadacol that made him famous outside Louisiana. For his "Hadacol Caravan" touring shows (the last of the big-time "medicine shows"), LeBlanc brought in Hollywood celebrities, including such luminaries as Milton Berle, Lucille Ball, Mickey Rooney, Bob Hope, Cesar Romero, Dorothy Lamour, Carmen Miranda, Minnie Pearl, George Burns and Gracie Allen, Judy Garland, Jack Dempsey, Chico Marx, Hank Williams and Jimmy Cagney to help him market the product. He also sponsored a separate touring show featuring notable Jazz and Blues musicians to attract Black customers. Admission to the Hadacol gala was two Hadacol boxtops for adults, one for children (Considering that the 8 ounce bottle cost $1.25 and the "family size" 24 ounce bottle cost $3.50 each during the late 1940's, this was not cheap). Sales of the tonic at the shows was brisk. According to musician Weldon "Big Bill" Lister, who performed in the Hadacol Caravan, "The only way you could get into that show was with a Hadacol boxtop, And believe me, we played to crowds of ten, twelve thousand people a night. Back in those days there wasn't many auditoriums that would hold that many people. We played ball parks, race tracks - you know anywhere where they had enough big bleachers to handle those kind of crowds." The final show was on 17 September 1951. # Downfall In a 15-month period ending in March 1951, LeBlanc sold more than $3,600,000 worth of the tonic. In another six months, after LeBlanc sold his interest of the LeBlanc Corporation (Hadacol's parent company) to investors for $8,200,000 , the enterprise collapsed under the weight of debtors. It was discovered all too late that LeBlanc was spending more for advertising by that point than he was taking in as receipts (turning its $3,600,000 profit into a $1,800,000 second-quarter loss), had concealed both $2,000,000 in unpaid bills and a $656,151 tax debt, and another $2,000,000, listed in the ledgers as "Accounts Receivable", were cases of the tonic out on consignment, much of which was being shipped back . In an official court statement, the Federal Trade Commission stated that the publicity behind the tonic was "false, misleading and deceptive in representing the nostrum as an effective treatment and cure for scores of ailments and diseases." The ensuing bad publicity played a contributing factor to LeBlanc losing a Gubernatorial election, and effectively halted his future chances for Governor of Louisiana. Martin Gardner's In the Name of Science (1952) mentions an interview that LeBlanc gave on Groucho Marx's radio program: - When Groucho asked him what Hadacol was good for, LeBlanc gave an answer of startling honesty. "It was good," the senator said, "for five and a half million for me last year." Today, the name "Hadacol" has become synonymous with any panaceas or "cure-alls" of dubious origin. # Trivia - A capsule version of Hadacol was briefly produced, consisting solely of a B-Vitamin and mineral mixture. - In 1954, after the Hadacol fiasco, LeBlanc tried to re-enter the patent medicine market with a lemon flavored non-alcoholic vitamin tonic named "Kary-On". Unlike Hadacol, it quickly vanished from production. - In 1976, "Hadacol" Multi-vitamins were distributed by the Atlanta, Georgia based "Hadacol Corporation" in an unsuccessful attempt to revive the brand name. - Paul Schrader wrote an (as of yet) unproduced script entitled Eight Scenes from the Life of Hank Wlliams. It includes a sequence on his performances with the Hadacol Caravan. # Influences - Hadacol was the subject of several Country, R&B and Cajun tunes of the time, such as "Hadacol Boogie" which was covered by a number of musical acts (notably Bill Nettles and His Dixie Blue Boys and, more recently, Jerry Lee Lewis), "Hadacol (That's All)" by the Treniers, "Hadacol Bounce" by Professor Longhair, "Drinkin' Hadacol" by "Little Willie" Littlefield, "Everybody Loves That Hadacol" by Tiny Hill and His Orchestra, "Valse de Hadacol" by Cajun musician/composer Harry Choates and "Hadacol Corners" by Slim Willet (the B-Side of the recording was the soon-to-be classic "Don't Let the Stars Get In Your Eyes"). - In the late 1990's, the American Country Rock band "Big Iron", seeking a more Country themed image, changed the band's name to "Hadacol" . The cover of their 1999 debut CD, Better Than This, is based on the label used on the tonic bottles. Another music group, a Canadian Rockabilly quintet named "The Twilighters", changed their name to "The Hadacol Cowboys" . - In 2005, Brent Green created an animated short entitled Hadacol Christmas. The animator describes the thread-bare 12 minute film this way: "Santa Claus invents Christmas with a belly full of cough syrup and a head full of dying crows." . Mr. Green posted the film on YouTube in two parts (Part 1 Part 2). - The town of Midkiff, in Upton County, Texas was supposedly to have been named "Hadacol Corner", but the U.S. Postal Service objected to the name (presumably on the grounds of a registered brand name being used for the name of a town) . - "Hadacol Boogie" was covered in 2006 on Jerry Lee Lewis' "Last Man Standing" album. Jerry Lee was joined on the cut by the bluesman Buddy Guy, also a native of Louisiana. # Listen to - "Valse de Hadacol" by Leroy "Happy Fats" LeBlanc (no relation to Dudley LeBlanc) at Cajun Music mp3	Hadacol Hadacol was a patent medicine marketed as a vitamin supplement. Its principal attraction, however, was that it contained 12 percent alcohol (listed on the tonic bottle's label as a "preservative"), which made it quite popular in the dry counties of the southern United States. It was the product of four-term Louisiana state Senator Dudley J. LeBlanc (1894-1971), a Democrat from Abbeville in Vermilion Parish. He was not a medical doctor, nor a registered pharmacist, but had a strong talent for self-promotion. Time Magazine once described him as "...a stem-winding salesman who knows every razzle-dazzle switch in the pitchman's trade". [1] # Origins LeBlanc conceived the idea that became "Hadacol" in New Orleans, when he injured a foot. He asked a doctor to give him medication for pain: then he found that what the doctor gave him was a B-vitamin elixir, which he proposed to duplicate with a few changes and market it to a mass consumer market (Years later, reports arose that LeBlanc offered the doctor a share of the business, who refused. On a return visit, LeBlanc allegedly stole a bottle of the medicine when the nurse had left the room). [2] LeBlanc said that his research showed that multivitamins taken collectively would yield greater results than a single vitamin for a specific problem. # Dosage The label on the tonic's bottle clearly stated that the recommended dosage (1 tablespoonful taken 4 times a day) was to be taken "...in a 1/2 glass of water after meals and before retiring". However, some pharmacies in dry counties were known to sell it by the shot-glass. In Northbrook, Illinois, a suburb of Chicago, sales of Hadacol were limited to liquor stores. [1] One of the tonic's unusual ingredients, "Diluted Acid Hydrochloric", is what is known as a "hydrochloric wash": a heavily diluted form of the acid that opens the arteries and allows the body's quicker absorption of the other ingredients, including the 12 percent alcohol "preservative". # Promotion LeBlanc created the name "Hadacol" from his former business, the Happy Day Company, maker of Happy Day Headache Powders (which had been seized by the FDA) and Dixie Dew Cough Syrup. "Happy" became "HA", "Days" became "DA," "Company" became "CO", and his own last name "LeBlanc" provided the "L". Hence the created named was "Hadacol." [2] However, when LeBlanc was asked about the name, he would often joke, "Well, I hadda' call (Hadacol) it something!" A two-page advertisement for Hadacol appeared in the centerfold of the 1951 edition of Grier's Almanac, an annual publication marketed to farmers in the Southern USA. The ad's headline read (in very large type): - Don't Be Satisfied With Symptomatic Relief! It's Possible to RELIEVE THE CAUSE OF YOUR AILMENTS When Lack Of Vitamins B1, B2, Iron and Niacin Cause Stomach Disturbances, Gas, Heartburn, Indigestion, Nagging Aches and Pains, and Certain Nervous Disorders. The ad continued with testimonials and a glowing plug for Senator LeBlanc, stressing the curative powers of Hadacol for a number of ailments "...due to lack of Vitamins B1, B2, Iron and Niacin". LeBlanc promoted the tonic as a "Dietary Supplement" instead of a medicine, stating that it was "...formulated as an Aid to Nature in rebuilding the Pep, Strength and Energy of Buoyant Health when the System is deficient in the Vitamins and Minerals found in this Tonic..."[3] The American Medical Association was not as appreciative. In an official press release in 1951, the AMA stated, "It is hoped that no doctor will be uncritical enough to join in the promotion of Hadacol. It is difficult to imagine how one could do himself or his profession greater harm from the standpoint of the abuse of the trust of a patient suffering from any condition. Hadacol is not a specific medication. It is not even a specific preventive measure." [4] LeBlanc flooded the airwaves with testimonials to the powers of the seemingly miraculous (yet foul tasting) brown liquid and turned the jingle called "Hadacol Boogie" into a popular recording. Promotional items included various flyers, signs and clocks, a "Captain Hadacol" comic book, an almanac, plastic thimbles printed with the Hadacol logo, glasses used for taking the diluted mixture, and a stamped metal token redeemable for 25 cents towards the purchase of any bottle of Hadacol (LeBlanc brazenly placed his own portrait on the front of the token, and the trademarked logo on the back). These items, along with the Hadacol bottles and the boxes they were packaged in, are now much sought-after items, and fetch high prices among collectors of Southern memorabilia and medical quackery. In 1950, LeBlanc offered a handsome financial incentive to anyone who could provide him with a parrot that was trained to say "Polly wants Hadacol!" The parrot was to be exhibited at promotions. The offer included the following: - The owner of such a bird, if selected, will be given a reasonable compensation on a contract basis. The owner and the parrot will travel in a limousine with the parrot's name engraved in gold on the door and will stay only at the best hotels. The parrot will be furnished a gold cage and its life insured. The parrot will visit large drugstores, perform at conventions, etc., and may be presented on radio and television. The Le Blanc Corporation has a triple A high credit rating.[5] # The Hadacol Caravan LeBlanc was an entrepreneur in other areas too, but it is Hadacol that made him famous outside Louisiana. For his "Hadacol Caravan" touring shows (the last of the big-time "medicine shows"), LeBlanc brought in Hollywood celebrities, including such luminaries as Milton Berle, Lucille Ball, Mickey Rooney, Bob Hope, Cesar Romero, Dorothy Lamour, Carmen Miranda, Minnie Pearl, George Burns and Gracie Allen, Judy Garland, Jack Dempsey, Chico Marx, Hank Williams and Jimmy Cagney to help him market the product. He also sponsored a separate touring show featuring notable Jazz and Blues musicians to attract Black customers. Admission to the Hadacol gala was two Hadacol boxtops for adults, one for children (Considering that the 8 ounce bottle cost $1.25 and the "family size" 24 ounce bottle cost $3.50 each during the late 1940's, this was not cheap). Sales of the tonic at the shows was brisk. According to musician Weldon "Big Bill" Lister, who performed in the Hadacol Caravan, "The only way you could get into that show was with a Hadacol boxtop, And believe me, we played to crowds of ten, twelve thousand people a night. Back in those days there wasn't many auditoriums that would hold that many people. We played ball parks, race tracks - you know anywhere where they had enough big bleachers to handle those kind of crowds." The final show was on 17 September 1951.[6] # Downfall In a 15-month period ending in March 1951, LeBlanc sold more than $3,600,000 worth of the tonic. In another six months, after LeBlanc sold his interest of the LeBlanc Corporation (Hadacol's parent company) to investors for $8,200,000 [7] [8], the enterprise collapsed under the weight of debtors. It was discovered all too late that LeBlanc was spending more for advertising by that point than he was taking in as receipts (turning its $3,600,000 profit into a $1,800,000 second-quarter loss), had concealed both $2,000,000 in unpaid bills and a $656,151 tax debt, and another $2,000,000, listed in the ledgers as "Accounts Receivable", were cases of the tonic out on consignment, much of which was being shipped back [9]. In an official court statement, the Federal Trade Commission stated that the publicity behind the tonic was "false, misleading and deceptive in representing the nostrum as an effective treatment and cure for scores of ailments and diseases." The ensuing bad publicity played a contributing factor to LeBlanc losing a Gubernatorial election, and effectively halted his future chances for Governor of Louisiana. Martin Gardner's In the Name of Science (1952) mentions an interview that LeBlanc gave on Groucho Marx's radio program: - When Groucho asked him what Hadacol was good for, LeBlanc gave an answer of startling honesty. "It was good," the senator said, "for five and a half million for me last year." Today, the name "Hadacol" has become synonymous with any panaceas or "cure-alls" of dubious origin. # Trivia - A capsule version of Hadacol was briefly produced, consisting solely of a B-Vitamin and mineral mixture. - In 1954, after the Hadacol fiasco, LeBlanc tried to re-enter the patent medicine market with a lemon flavored non-alcoholic vitamin tonic named "Kary-On". [10] Unlike Hadacol, it quickly vanished from production. - In 1976, "Hadacol" Multi-vitamins were distributed by the Atlanta, Georgia based "Hadacol Corporation" in an unsuccessful attempt to revive the brand name. - Paul Schrader wrote an (as of yet) unproduced script entitled Eight Scenes from the Life of Hank Wlliams. It includes a sequence on his performances with the Hadacol Caravan. [11] # Influences - Hadacol was the subject of several Country, R&B and Cajun tunes of the time, such as "Hadacol Boogie" which was covered by a number of musical acts (notably Bill Nettles and His Dixie Blue Boys and, more recently, Jerry Lee Lewis), "Hadacol (That's All)" by the Treniers, "Hadacol Bounce" by Professor Longhair, "Drinkin' Hadacol" by "Little Willie" Littlefield, "Everybody Loves That Hadacol" by Tiny Hill and His Orchestra, "Valse de Hadacol" by Cajun musician/composer Harry Choates and "Hadacol Corners" by Slim Willet (the B-Side of the recording was the soon-to-be classic "Don't Let the Stars Get In Your Eyes"). - In the late 1990's, the American Country Rock band "Big Iron", seeking a more Country themed image, changed the band's name to "Hadacol" [12]. The cover of their 1999 debut CD, Better Than This, is based on the label used on the tonic bottles. Another music group, a Canadian Rockabilly quintet named "The Twilighters", changed their name to "The Hadacol Cowboys" [13]. - In 2005, Brent Green created an animated short entitled Hadacol Christmas. The animator describes the thread-bare 12 minute film this way: "Santa Claus invents Christmas with a belly full of cough syrup and a head full of dying crows." [14]. Mr. Green posted the film on YouTube in two parts (Part 1 Part 2). - The town of Midkiff, in Upton County, Texas was supposedly to have been named "Hadacol Corner", but the U.S. Postal Service objected to the name (presumably on the grounds of a registered brand name being used for the name of a town) [15] [16]. - "Hadacol Boogie" was covered in 2006 on Jerry Lee Lewis' "Last Man Standing" album. Jerry Lee was joined on the cut by the bluesman Buddy Guy, also a native of Louisiana. # Listen to - "Valse de Hadacol" by Leroy "Happy Fats" LeBlanc (no relation to Dudley LeBlanc) at Cajun Music mp3	https://www.wikidoc.org/index.php/Hadacol
b0a46d9ad86526f0567dd87511d9e33ba596676f	wikidoc	Hagenia	Hagenia Hagenia abyssinica is a species of flowering plant native to the high-elevation Afromontane regions of central and eastern Africa. It also has a disjunct distribution in the high mountains of East Africa from Sudan and Ethiopia in the north, through Kenya, Uganda, Rwanda, Burundi, Democratic Republic of Congo, and Tanzania, to Malawi and Zambia in the south. It is known in English as African redwood, brayera, cusso, hagenia, or kousso, in Amharic as kosso, and in Swahili as mdobore or mlozilozi. It is the sole species of genus Hagenia, and its closest relative is the Afromontane genus Leucosidea. Synonyms include Banksia abyssinica, Brayera anthelmintica, Hagenia abyssinica var. viridifolia and Hagenia anthelmintica. It is a slender tree up to 20 m in height, with a short trunk, thick branches, and thick, peeling bark. The leaves are up to 40 cm long, compound with 7-13 leaflets, each leaflet about 10 cm long with a finely serrated margin, green above, silvery-haired below. The flowers are white to orange-buff or pinkish-red, produced in panicles 30-60 cm long. It is generally found from 2000-3000 m elevation, in areas receiving 1000-1500 mm of rainfall annually. It can be found growing in mixed afromontane forest with Podocarpus, Afrocarpus, and other trees, and in drier afromontane forests and woodlands where Hagenia is dominant, or in mixed stands of Hagenia and Juniperus procera. Hagenia is used as a food plant by the larvae of some Lepidoptera species including Turnip Moth. # Medicinal uses Kosso, kousso or cusso is a drug which consists of the panicles of the pistillate flowers of Hagenia. At the time of the eleventh edition of the Encyclopaedia Britannica, the drug was imported "in the form of cylindrical rolls, about 18 inches in length and 2 inches in diameter, and comprises the entire inflorescence or panicle kept in form by a band wound transversely round it." The active principle is koussin or kosin, C31H33O10, which is soluble in alcohol and alkalis, and may be given in doses of two grammes. Kosso is also used in the form of an unstrained infusion of the coarsely powdered flowers, which are swallowed with the liquid. It is considered to be an effective anthelmintic for pork tapeworm (Taenia solium). In its anthelmintic action it is similar to Male Fern (Dryopteris filix-mas). Use of Kosso was borrowed from Ethiopia, where as Richard Pankhurst quotes Merab as saying that "to mention it was to cover a quarter of that country's pharmacopeia." However, its primary use was, well into the 19th century, to combat human tapeworm infestations, which was endemic due to widespread consumption of dishes containing raw beef, such as kitfo and gored gored. Frequent doses of kosso, about once every two months, was the common cure. Richard Pankhurst cites numerous examples of this practice, noting that "the two-monthly event virtually constituted a holiday for the patient, who withdrew from all normal activity, the statement 'the master has taken his kosso,' being synonymous with 'he cannot receive you today.' Kosso-drinking in fact served as an excuse or justification for not keeping appointments, being used by the debtor who did not wish to meet his creditor, by the accused who wished to avoid going to court, and by the official who sought to delay answering the Emperor's summons." Kosso or ኮሶ in Amharic is also the name of the human tapeworm, Taenia saginata. Treatment with Hagenia is often unsuccessful resulting in only partial removal of the intestinal worm. # Notes - ↑ Richard Pankhurst, An Introduction to the Medical History of Ethiopia (Trenton: Red Sea Press, 1990), p. 104 - ↑ Richard Pankhurst, Economic History of Ethiopia (Addis Ababa: Haile Selassie I University, 1968), p. 631. # Further reading and external links - Hagenia abyssinica at the AgroForestry Tree Database (World Agroforestry Centre) - Eriksson, T., Hibbs, M. S., Yoder, A. D., Delwiche, C. F., & Donoghue, M. J. (2003). The Phylogeny of Rosoideae (Rosaceae) Based on Sequences of the Internal Transcribed Spacers (ITS) of Nuclear Ribosomal DNA and the TRNL/F Region of Chloroplast DNA. International Journal of Plant Science 164(2): 197–211 (PDF version). - Template:1911 de:Kosobaum	Hagenia Hagenia abyssinica is a species of flowering plant native to the high-elevation Afromontane regions of central and eastern Africa. It also has a disjunct distribution in the high mountains of East Africa from Sudan and Ethiopia in the north, through Kenya, Uganda, Rwanda, Burundi, Democratic Republic of Congo, and Tanzania, to Malawi and Zambia in the south. It is known in English as African redwood, brayera, cusso, hagenia, or kousso, in Amharic as kosso, and in Swahili as mdobore or mlozilozi. It is the sole species of genus Hagenia, and its closest relative is the Afromontane genus Leucosidea. Synonyms include Banksia abyssinica, Brayera anthelmintica, Hagenia abyssinica var. viridifolia and Hagenia anthelmintica. It is a slender tree up to 20 m in height, with a short trunk, thick branches, and thick, peeling bark. The leaves are up to 40 cm long, compound with 7-13 leaflets, each leaflet about 10 cm long with a finely serrated margin, green above, silvery-haired below. The flowers are white to orange-buff or pinkish-red, produced in panicles 30-60 cm long. It is generally found from 2000-3000 m elevation, in areas receiving 1000-1500 mm of rainfall annually. It can be found growing in mixed afromontane forest with Podocarpus, Afrocarpus, and other trees, and in drier afromontane forests and woodlands where Hagenia is dominant, or in mixed stands of Hagenia and Juniperus procera. Hagenia is used as a food plant by the larvae of some Lepidoptera species including Turnip Moth. # Medicinal uses Kosso, kousso or cusso is a drug which consists of the panicles of the pistillate flowers of Hagenia. At the time of the eleventh edition of the Encyclopaedia Britannica, the drug was imported "in the form of cylindrical rolls, about 18 inches in length and 2 inches in diameter, and comprises the entire inflorescence or panicle kept in form by a band wound transversely round it." The active principle is koussin or kosin, C31H33O10, which is soluble in alcohol and alkalis, and may be given in doses of two grammes. Kosso is also used in the form of an unstrained infusion of the coarsely powdered flowers, which are swallowed with the liquid. It is considered to be an effective anthelmintic for pork tapeworm (Taenia solium). In its anthelmintic action it is similar to Male Fern (Dryopteris filix-mas). Use of Kosso was borrowed from Ethiopia, where as Richard Pankhurst quotes Merab as saying that "to mention it was to cover a quarter of that country's pharmacopeia."[1] However, its primary use was, well into the 19th century, to combat human tapeworm infestations, which was endemic due to widespread consumption of dishes containing raw beef, such as kitfo and gored gored. Frequent doses of kosso, about once every two months, was the common cure. Richard Pankhurst cites numerous examples of this practice, noting that "the two-monthly event virtually constituted a holiday for the patient, who withdrew from all normal activity, the statement 'the master has taken his kosso,' being synonymous with 'he cannot receive you today.' Kosso-drinking in fact served as an excuse or justification for not keeping appointments, being used by the debtor who did not wish to meet his creditor, by the accused who wished to avoid going to court, and by the official who sought to delay answering the Emperor's summons."[2] Kosso or ኮሶ in Amharic is also the name of the human tapeworm, Taenia saginata. Treatment with Hagenia is often unsuccessful resulting in only partial removal of the intestinal worm. # Notes - ↑ Richard Pankhurst, An Introduction to the Medical History of Ethiopia (Trenton: Red Sea Press, 1990), p. 104 - ↑ Richard Pankhurst, Economic History of Ethiopia (Addis Ababa: Haile Selassie I University, 1968), p. 631. # Further reading and external links - Hagenia abyssinica at the AgroForestry Tree Database (World Agroforestry Centre) - Eriksson, T., Hibbs, M. S., Yoder, A. D., Delwiche, C. F., & Donoghue, M. J. (2003). The Phylogeny of Rosoideae (Rosaceae) Based on Sequences of the Internal Transcribed Spacers (ITS) of Nuclear Ribosomal DNA and the TRNL/F Region of Chloroplast DNA. International Journal of Plant Science 164(2): 197–211 (PDF version). - Template:1911 de:Kosobaum Template:WH Template:WS	https://www.wikidoc.org/index.php/Hagenia
347c06a7e1759105a145e7d73e046b5f31875c65	wikidoc	Hashish	Hashish Hashish. (from Arabic: حشيش Template:ArabDIN, lit. "grass"; also hash) is a preparation of cannabis composed of the compressed trichomes collected from the cannabis plant. It contains the same active ingredients but in higher concentrations than other parts of the plant such as the buds or the leaves. Psychoactive effects vary between types of hashish but are usually the same as those of other cannabis preparations such as marijuana. Hash is generally prohibited to the same extent as all other forms of cannabis. Hashish is often a solid or paste-like substance, of varying hardness and pliability, and will soften under heat. Its color can vary from green, black, reddish brown, or most commonly light to dark brown. It is consumed in much the same way as cannabis buds, used by itself in miniature smoking pipes, vaporized, hot knifed, smoked in a bong or bubbler, or smoked in joints mixed with tobacco, cannabis buds or other herbs. It can also be eaten alone (pure hash is described as having a spicy or peppery flavor) as well as used as an ingredient in food (baked into cookies or cakes, or added to stews and chocolate). Sale of hashish is illegal under federal law in United States and in most parts of the world; it has been decriminalized to some extent in a few countries, such as the Netherlands. # History It is believed that hash first originated from Central Asia, as this region was among the first to be populated by the cannabis plant, which may have originated in the Hindu Kush. More reliably, it may have originated in Northern India which also has a very long social tradition in the production of Hashish which is locally known as Charas. Traditionally, Cannabis sativa subsp. indica grows wild almost everywhere in the Indian sub-continent and special strains have been particularly cultivated for production of 'ganja' and 'hashish' particularly in Kerala, Rajasthan and the Himalayas. The earliest hashish was created without the use of sieves. The ancients would gently rub their palms and fingers on cannabis buds for hours while resin accumulated on their hands and then scrape that resin off. This sort of primitive harvesting is undertaken even today in the Cannabis growing farms of Manali, Naggar and Upper Himachal Pradesh. The earliest use of hashish was most likely from farmers scraping resin off of their hands after a day's harvest of commercial hemp and at that time hashish was normally eaten, not smoked. Hashshashin or hashish eaters ( there is no evidence about hashshashin means hashish eaters or they had used hashish in history, it's just a mystery ) , the Assassins of the Ismaili Persian fort of Alamut, were a secret society, a fraternal order designed to commit 'assassinations' and usurp the powers of the state. In Nishapur of the region of Khorassan, while studying under the Imam Mowaffaq Nishipuri, Hassan-i-Sabbah, founder of the order, suggested an agreement to Omar Kayyam and Nizam ul Mulk that if one of them (The Three Schoolmates) should succeed, the other two would share in the good turn of the Wheel of Fortune; eventually, Hassan would violate the agreement. The chilling shadow of the Assassins spread from Persia to the Mediterranean coast, its members prospering not only in their natural habitat but also in Syria where they came across the European Crusaders exercising a great influence upon them. In 1071, Hassan had joined the Ishmaelites whose members spread far and wide from Morocco to China and Zanzibar. Eventually, the Templars would fall prey to the king of France, Philip the Fair, and the Assassin's leader would be slain by order of the Great Khan..."Comparison of the general administration of the two orders -opponents though they were for a time in Syria- reveals much wherein they were virtually identical". Production of hash later spread to the Middle East (Lebanon), and from there to North Africa (most prominently Algeria, though in post-colonial times Moroccan production has dominated) and then South Asia (mostly in India and Pakistan). The word assassin may have been derived from the Arabic word حشّاشين (haššāšīn), or "Hashshāshīn". The Hashashin were allegedly inspired to commit murder under the influence of hashish ( there is no evidence about eating or using hashish in history, it's just a mystery) . The legend of hashish-eating assassins began with a vague mention by Marco Polo, and was embellished by 19th century French and American writers, fascinated by orientalism and eager to present hashish as a menace. The legend gained great popularity especially by Charles Baudelaire in his Artificial Paradises of 1857. Others argue that the term could have been created due to political reasons, in order to discredit the sect. It has also been suggested that if hashish were in fact consumed, it had been adulterated with stronger materials, the effects of hashish being well-known and easily recognizable at that time and place. No reports of statistical linkage between hashish and assassins or terror have been published anywhere in the last century. Consumption of hashish saw an increase in the 20th century, in Europe and America, associated with the hippie scene. Hashish use declined significantly in the United States starting in the 1980s for several reasons, including U. S. political pressures against Afghanistan and the ensuing Soviet invasion, a huge jump in price, and the success of marijuana cultivators in North America with new growing methods for increasing THC production, such as growing marijuana indoors. # Manufacturing processes Hashish is made from tetrahydrocannabinol-rich glandular hairs known as trichomes, as well as varying amounts of cannabis flower and leaf fragments. The flowers of a mature female plant contain the most trichomes, though trichomes are found on other parts of the plant. Certain strains of cannabis are cultivated specifically for their ability to produce large amounts of trichomes. The resin reservoirs of the trichomes, sometimes erroneously called pollen, are separated from the plant through various methods. The resulting concentrate is formed into blocks of hashish, which can be easily stored and transported. Alternatively, the powder consisting of uncompressed, dry trichomes is often referred to as kief instead of hashish. Mechanical separation methods use physical action to remove the trichomes from the plant. Sieving over a fine screen is a vital part of most methods. The plants may be sifted by hand or in motorized tumblers. Hash made in this way is sometimes called dry sift. Finger hash is produced by rolling the ripe trichome-covered flowers of the plant between the fingers and collecting the resin that sticks to the fingers. Yet another means of harvest is effected by having workers bustle through the cannabis fields wearing specially designed leather aprons, upon which the trichomes collect and adhere. Trichomes and resins can also be collected passively through cleaning of scissors that have been used to cut the plant, or containers like a kief-box used to store it. Ice water separation is a more modern mechanical separation method which submerges the plant in ice and water and stirs the mixture. Trichomes are broken off the plant as the ice moves, while the low temperature make the trichomes more brittle so they break off easily. The waste plant matter, detached trichomes, and water are separated by filtering through a series of increasingly fine screens. Kits are commercially available which provide a series of filter screens meant to fit inside standard bucket sizes. Hash made in this way is sometimes called ice hash, or bubble hash. Chemical separation methods generally use a solvent to dissolve the desirable resins in the plant while not dissolving undesirable components. The solid plant material is then filtered out of the solution and discarded. The solvent may then be evaporated, leaving behind the desirable resins. As THC is fat-soluble, it also dissolves in butter, which can then be used for cooking (see hash cookies and Alice B. Toklas brownies). The product of chemical separations is more commonly referred to as honey oil, hash oil, or just oil. Some believe that hash oil is best avoided, due both to the dangerous nature of its production and the fear of residual chemicals left in the oil by the solvent. # Quality The main factors affecting quality are potency and purity. Different cannabis plants will produce resins with unique chemical profiles that vary in potency. Some forms of hashish are described as producing a "body high" while others are more "cerebral". This depends on the genetic strain and relative amount of different cannabis plants used as well as the manufacturing process involved. Tiny pieces of leaf matter or even purposefully added adulterants introduced when the hash is being produced will reduce the purity of the material. The THC content of hashish usually ranges from 15–20%, and that of hash oil from 30–40%. Fresh hashish of good quality is soft and pliable and becomes progressively harder and less potent as it oxidizes. Hash is generally said to be black, brown or blond. There is also hashish of greenish or reddish hue. A green tinge may indicate that the hashish is impure, has been cut with low-quality leaf or contains high quantities of chlorophyll. A yellow tint can indicate presence of cannabis pollen, which has a sandy color. Low quality forms of hash often contain adulterants used as cutting agents added to exaggerate the value of hash through increasing the mass or including other cheaper drugs.. Such forms usually possess a low potency, may have an unpleasant strangeness in taste and feel, and produce hard, dark "cinders" in the ash which should be soft and white. Adulterants in hash may range from waste material from the cannabis plant (generally not harmful) to products such as food oils and soap, hence the name soap bar. The low quality may lead one to smoke more to get the same effect, increasing exposure to carbon monoxide and adverse effects upon the lungs. A general rule of thumb is that good hashish produces effects which should be rapidly, unmistakably apparent, even with experienced users who have developed tolerance to THC; being unsure of the effects or wanting to use more within a short amount of time means the hashish is either very weak and/or, more likely, adulterated. Some users have started boiling their hash in water for a few minutes and then drying it before smoking. This is thought to remove all water-soluble adulterants while the psychoactive cannabinols remain intact as the temperature is not sufficient to destroy them and they are not soluble in water. The smoke and ashes of burnt hash should be light gray or white in color. Dark, acrid smoke and poor ease of inhaling smoke signify that the material is contaminated. It is always best to compost any such unacceptable hashish rather than continue using it in hopes of achieving a high. # Hashish by region ## Production Hashish is traditionally produced in desert conditions. It is traditionally found in a belt extending from North Africa , Egypt to North India and into Central Asia. The primary hash-producing countries are Afghanistan, Pakistan, Nepal, Morocco, Lebanon and India. Charas is the primary product. Charas, a substance that is hand-rubbed directly from the cannabis plant, is generally produced in Nepal and India. Today, the word charas is common word for hash in a majority of India, despite the fact that other methods may be used than the hand-rubbed method. A visitor to the Rif Mountains and the town of Ketama in Morocco in December 1976 described the production of hashish. Workers rubbed the leaves of the cannabis plant over fine muslin fabric. In unheated huts, each worker had his hands and arms inside a regular one hundredweight (50 kg) plastic fertiliser bag containing twigs and leaves of the cannabis plant. In the mouth of the bag was a plastic washing-up bowl. Stretched over the bowl was a sheet of "zero-zero" grade muslin. The worker rubbed the leaves of the cannabis plant over the muslin, resulting in a fine powder ending up in the bowl. When 100 grams of the powder was collected it was then wrapped in more fine muslin, put onto a heated metal plate, and rolled down with a bottle. This process produced a slightly sticky solid brown mass in the form of a square slab, around half the size of a paperback book and about ½ cm thick. This block was wrapped in cellophane. Sellers of this Moroccan hashish pointed to the imprint of the muslin on the surface of the block, and declared it proof that the product was "zero-zero", top quality. In Afghanistan there is a method of making hash that resembles charas. First, cannabis resin is placed on a large heated mortar, then the resin is threshed with a heavy object. The result is a very gooey, sticky black hash. This method is mostly used in villages around the Hindu Kush mountain region. Hash is also produced now in the deserts of northern Mexico; however, the demand for it and thus amount produced is insignificant compared to that for "fresh" Mexican marijuana, especially into the lucrative North American market. ## Consumption Hashish was always the variety of preference in Europe (although this preference is slowly changing towards the buds of the plant) , it is basically the exclusive form of THC in the Middle East and was widely available in North Africa and parts of Asia. It is less preferred by cannabis users in the US and other producing nations. Hashish is more compact than marijuana, it keeps better, and is easier to smuggle than marijuana. When it has been smuggled by amateurs, it often suffers from long periods of bad storage, so the quality can vary considerably. Older hashish can easily be recognized as it is hard and has no smell (heating with a lighter is a common test). By the 1990s, the use of marijuana in the developed world was increasing, as more potent versions were being grown. The Cannabis Cup held every year in Amsterdam attempts to evaluate the quality of the latest varieties. In France and the German- and French-speaking parts of Switzerland, this is known as Marocain (Maroc meaning "Morocco" in French). In Germany it is known colloquially as "Piece". In Spain it is called Costo, Chocolate, Grifa or Hachís. In the United Kingdom, it is variously known as brown (also a name for heroin in some parts of the UK), hash, resin, solid, and block. In the Netherlands, this is called Hasj or Assi (although coffee shops will maintain a wide variety of types, i.e.: Polm, Blond, Tempel Bol, Isolator, Zero-Zero or Waterwerks, generally relating to either the method of production, country of origin or type of marijuana used.). In Brazil, it is commonly called haxa. Also, there is a branch of nearly white powder hash (pollen or kief hash) that is the result of not stamping the raw material for the more common compressed hashish. Soft hash is usually dark brown to black in color and goes under the name black in France, squidgey or soft black (named due to the color and properties of the hash) in the UK. The very potent Paki Black is so named because it originates in Pakistan. Soft, dark hash in the Netherlands is normally referred to as Afghan. Common Kashmiri brands are Citral and Fungus. Hashish use is experiencing a resurgence in parts of North America (especially the Pacific Northwest) with the use and commercial availability of ice-water extraction kits. # Preparation and methods of use Like ordinary cannabis preparations, hashish is usually smoked, though it can also be eaten or vaporised. Hash is sometimes prepared for smoking by heating it with a flame for a couple of seconds, producing some bubbling or sizzling. It then softens and can be crumbled into tiny pieces or formed into shapes to obtain maximum surface area when burning. A sharp razor knife can be used to divide hard unheated hash into small slender pieces. If the material is of the right consistency, it can be ground up with a marijuana grinder. Although heating may cause more THC to be released in its active form. ## Vaporization Used with hashish as with any cannabis, tobacco or other herb material, a vaporizer can extract cannabinoids at a temperature of 350°F./150°C., protecting against loss of this ingredient which occurs in burning, and eliminating carbon monoxide and other combustion toxins. Since hashish is solid, it's surface area is enlarged by the user, for a maximum cannabinoid vaporization. ## "Knife Hits" Hash can be placed on very hot pieces of metal and the resulting vapor inhaled. "Knife hits" is a method that involves heating up knives on a stove, crushing a little ball of the hash between them and inhaling the released vapor through a tube or straw. Hash cones is a method where a piece of hash is attached to a pin or metal wire and then heated. ## One-hitter (semivaporizer) The next lowest temperature is achieved with a narrow-diameter, screened-crater utensil-- one-hitter, minitoke, kiseru or midwakh-- where the practiced user sucks the air slowly enough to assure slow, low-temperature burning, so that the cannabinol in any part of the hashish has time to vaporize from being heated by an already burning adjacent part of the hashish (semivaporizer). A butane lighter should be used instead of matches to permit frequent, very brief relightings, and a long tube (such as those found on hookahs) added giving the heated aerosol a longer distance to travel, i.e. more time to cool down before reaching the user's trachea. ## Dabous A piece of hash may be ignited by cigarette coals or other means and placed inside a container. The smoke that collects inside can then be inhaled. Dabous or Khabour, but most commonly "shi-sha" (glass in Arabic) is a North African technique. In Canada this technique is commonly referred to as "Bots" or "BTs" ("Bottle-Tokes"). ## Mixtures Often hash is mixed with tobacco, cannabis or another herb, and the combination rolled up into a cigarette or burned in a large pipe by users impatient to get it burning, a procedure best avoided as the high burning temperature results in major loss of THC (and the exposure to nicotine can result in tobacco addiction). Smoked by itself, hash usually creates a stronger psychoactive effect on the user.	Hashish Template:This Hashish. (from Arabic: حشيش Template:ArabDIN, lit. "grass"; also hash) is a preparation of cannabis composed of the compressed trichomes collected from the cannabis plant. It contains the same active ingredients but in higher concentrations than other parts of the plant such as the buds or the leaves. Psychoactive effects vary between types of hashish but are usually the same as those of other cannabis preparations such as marijuana. Hash is generally prohibited to the same extent as all other forms of cannabis. Hashish is often a solid or paste-like substance, of varying hardness and pliability, and will soften under heat. Its color can vary from green, black, reddish brown, or most commonly light to dark brown. It is consumed in much the same way as cannabis buds, used by itself in miniature smoking pipes, vaporized, hot knifed, smoked in a bong or bubbler, or smoked in joints mixed with tobacco, cannabis buds or other herbs. It can also be eaten alone (pure hash is described as having a spicy or peppery flavor) as well as used as an ingredient in food (baked into cookies or cakes, or added to stews and chocolate). Sale of hashish is illegal under federal law in United States and in most parts of the world; it has been decriminalized to some extent in a few countries, such as the Netherlands. # History It is believed that hash first originated from Central Asia, as this region was among the first to be populated by the cannabis plant, which may have originated in the Hindu Kush[citation needed]. More reliably, it may have originated in Northern India which also has a very long social tradition in the production of Hashish which is locally known as Charas. Traditionally, Cannabis sativa subsp. indica grows wild almost everywhere in the Indian sub-continent and special strains have been particularly cultivated for production of 'ganja' and 'hashish' particularly in Kerala, Rajasthan and the Himalayas.[citation needed] The earliest hashish was created without the use of sieves. The ancients would gently rub their palms and fingers on cannabis buds for hours while resin accumulated on their hands and then scrape that resin off. This sort of primitive harvesting is undertaken even today in the Cannabis growing farms of Manali, Naggar and Upper Himachal Pradesh. The earliest use of hashish was most likely from farmers scraping resin off of their hands after a day's harvest of commercial hemp and at that time hashish was normally eaten, not smoked. Hashshashin or hashish eaters ( there is no evidence about hashshashin means hashish eaters or they had used hashish in history, it's just a mystery ) , the Assassins of the Ismaili Persian fort of Alamut, were a secret society, a fraternal order designed to commit 'assassinations' and usurp the powers of the state. In Nishapur of the region of Khorassan, while studying under the Imam Mowaffaq Nishipuri, Hassan-i-Sabbah, founder of the order, suggested an agreement to Omar Kayyam and Nizam ul Mulk that if one of them (The Three Schoolmates) should succeed, the other two would share in the good turn of the Wheel of Fortune; eventually, Hassan would violate the agreement. The chilling shadow of the Assassins spread from Persia to the Mediterranean coast, its members prospering not only in their natural habitat but also in Syria where they came across the European Crusaders exercising a great influence upon them. In 1071, Hassan had joined the Ishmaelites whose members spread far and wide from Morocco to China and Zanzibar. Eventually, the Templars would fall prey to the king of France, Philip the Fair, and the Assassin's leader would be slain by order of the Great Khan..."Comparison of the general administration of the two orders -opponents though they were for a time in Syria- reveals much wherein they were virtually identical". [1] Production of hash later spread to the Middle East (Lebanon), and from there to North Africa (most prominently Algeria, though in post-colonial times Moroccan production has dominated) and then South Asia (mostly in India and Pakistan). The word assassin may have been derived from the Arabic word حشّاشين (haššāšīn), or "Hashshāshīn". The Hashashin were allegedly inspired to commit murder under the influence of hashish ( there is no evidence about eating or using hashish in history, it's just a mystery) . The legend of hashish-eating assassins began with a vague mention by Marco Polo, and was embellished by 19th century French and American writers, fascinated by orientalism and eager to present hashish as a menace. The legend gained great popularity especially by Charles Baudelaire in his Artificial Paradises of 1857. Others argue that the term could have been created due to political reasons, in order to discredit the sect. It has also been suggested that if hashish were in fact consumed, it had been adulterated with stronger materials, the effects of hashish being well-known and easily recognizable at that time and place. No reports of statistical linkage between hashish and assassins or terror have been published anywhere in the last century. Consumption of hashish saw an increase in the 20th century, in Europe and America, associated with the hippie scene. Hashish use declined significantly in the United States starting in the 1980s for several reasons, including U. S. political pressures against Afghanistan and the ensuing Soviet invasion, a huge jump in price, and the success of marijuana cultivators in North America with new growing methods for increasing THC production, such as growing marijuana indoors. # Manufacturing processes Hashish is made from tetrahydrocannabinol-rich glandular hairs known as trichomes, as well as varying amounts of cannabis flower and leaf fragments. The flowers of a mature female plant contain the most trichomes, though trichomes are found on other parts of the plant. Certain strains of cannabis are cultivated specifically for their ability to produce large amounts of trichomes. The resin reservoirs of the trichomes, sometimes erroneously called pollen, are separated from the plant through various methods. The resulting concentrate is formed into blocks of hashish, which can be easily stored and transported. Alternatively, the powder consisting of uncompressed, dry trichomes is often referred to as kief instead of hashish. Mechanical separation methods use physical action to remove the trichomes from the plant. Sieving over a fine screen is a vital part of most methods. The plants may be sifted by hand or in motorized tumblers. Hash made in this way is sometimes called dry sift. Finger hash is produced by rolling the ripe trichome-covered flowers of the plant between the fingers and collecting the resin that sticks to the fingers. Yet another means of harvest is effected by having workers bustle through the cannabis fields wearing specially designed leather aprons, upon which the trichomes collect and adhere. Trichomes and resins can also be collected passively through cleaning of scissors that have been used to cut the plant, or containers like a kief-box used to store it. Ice water separation is a more modern mechanical separation method which submerges the plant in ice and water and stirs the mixture. Trichomes are broken off the plant as the ice moves, while the low temperature make the trichomes more brittle so they break off easily. The waste plant matter, detached trichomes, and water are separated by filtering through a series of increasingly fine screens. Kits are commercially available which provide a series of filter screens meant to fit inside standard bucket sizes. Hash made in this way is sometimes called ice hash, or bubble hash. Chemical separation methods generally use a solvent to dissolve the desirable resins in the plant while not dissolving undesirable components. The solid plant material is then filtered out of the solution and discarded.[2] The solvent may then be evaporated, leaving behind the desirable resins. As THC is fat-soluble, it also dissolves in butter, which can then be used for cooking (see hash cookies and Alice B. Toklas brownies).[3] The product of chemical separations is more commonly referred to as honey oil, hash oil, or just oil. Some believe that hash oil is best avoided, due both to the dangerous nature of its production and the fear of residual chemicals left in the oil by the solvent. # Quality The main factors affecting quality are potency and purity. Different cannabis plants will produce resins with unique chemical profiles that vary in potency. Some forms of hashish are described as producing a "body high" while others are more "cerebral". This depends on the genetic strain and relative amount of different cannabis plants used as well as the manufacturing process involved. Tiny pieces of leaf matter or even purposefully added adulterants introduced when the hash is being produced will reduce the purity of the material. The THC content of hashish usually ranges from 15–20%, and that of hash oil from 30–40%.[4] Fresh hashish of good quality is soft and pliable and becomes progressively harder and less potent as it oxidizes. Hash is generally said to be black, brown or blond. There is also hashish of greenish or reddish hue. A green tinge may indicate that the hashish is impure, has been cut with low-quality leaf or contains high quantities of chlorophyll. A yellow tint can indicate presence of cannabis pollen, which has a sandy color. Low quality forms of hash often contain adulterants used as cutting agents added to exaggerate the value of hash through increasing the mass or including other cheaper drugs.[5]. Such forms usually possess a low potency, may have an unpleasant strangeness in taste and feel, and produce hard, dark "cinders" in the ash which should be soft and white. Adulterants in hash may range from waste material from the cannabis plant (generally not harmful) to products such as food oils and soap, hence the name soap bar. The low quality may lead one to smoke more to get the same effect, increasing exposure to carbon monoxide and adverse effects upon the lungs. A general rule of thumb is that good hashish produces effects which should be rapidly, unmistakably apparent, even with experienced users who have developed tolerance to THC; being unsure of the effects or wanting to use more within a short amount of time means the hashish is either very weak and/or, more likely, adulterated. Some users have started boiling their hash in water for a few minutes and then drying it before smoking. This is thought to remove all water-soluble adulterants while the psychoactive cannabinols remain intact as the temperature is not sufficient to destroy them and they are not soluble in water.[6] The smoke and ashes of burnt hash should be light gray or white in color. Dark, acrid smoke and poor ease of inhaling smoke signify that the material is contaminated. It is always best to compost any such unacceptable hashish rather than continue using it in hopes of achieving a high.[citation needed] # Hashish by region ## Production Hashish is traditionally produced in desert conditions. It is traditionally found in a belt extending from North Africa , Egypt to North India and into Central Asia[citation needed]. The primary hash-producing countries are Afghanistan, Pakistan, Nepal, Morocco, Lebanon and India.[citation needed] Charas is the primary product. Charas, a substance that is hand-rubbed directly from the cannabis plant, is generally produced in Nepal and India. Today, the word charas is common word for hash in a majority of India, despite the fact that other methods may be used than the hand-rubbed method. A visitor to the Rif Mountains and the town of Ketama in Morocco in December 1976 described the production of hashish. Workers rubbed the leaves of the cannabis plant over fine muslin fabric. In unheated huts, each worker had his hands and arms inside a regular one hundredweight (50 kg) plastic fertiliser bag containing twigs and leaves of the cannabis plant. In the mouth of the bag was a plastic washing-up bowl. Stretched over the bowl was a sheet of "zero-zero" grade muslin. The worker rubbed the leaves of the cannabis plant over the muslin, resulting in a fine powder ending up in the bowl. When 100 grams of the powder was collected it was then wrapped in more fine muslin, put onto a heated metal plate, and rolled down with a bottle. This process produced a slightly sticky solid brown mass in the form of a square slab, around half the size of a paperback book and about ½ cm thick. This block was wrapped in cellophane. Sellers of this Moroccan hashish pointed to the imprint of the muslin on the surface of the block, and declared it proof that the product was "zero-zero", top quality. In Afghanistan there is a method of making hash that resembles charas. First, cannabis resin is placed on a large heated mortar, then the resin is threshed with a heavy object. The result is a very gooey, sticky black hash. This method is mostly used in villages around the Hindu Kush mountain region.[citation needed] Hash is also produced now in the deserts of northern Mexico; however, the demand for it and thus amount produced is insignificant compared to that for "fresh" Mexican marijuana, especially into the lucrative North American market. ## Consumption Hashish was always the variety of preference in Europe (although this preference is slowly changing towards the buds of the plant) , it is basically the exclusive form of THC in the Middle East and was widely available in North Africa and parts of Asia. It is less preferred by cannabis users in the US and other producing nations. Hashish is more compact than marijuana, it keeps better, and is easier to smuggle than marijuana. When it has been smuggled by amateurs, it often suffers from long periods of bad storage, so the quality can vary considerably. Older hashish can easily be recognized as it is hard and has no smell (heating with a lighter is a common test). By the 1990s, the use of marijuana in the developed world was increasing, as more potent versions were being grown. The Cannabis Cup held every year in Amsterdam attempts to evaluate the quality of the latest varieties. In France and the German- and French-speaking parts of Switzerland, this is known as Marocain (Maroc meaning "Morocco" in French). In Germany it is known colloquially as "Piece". In Spain it is called Costo, Chocolate, Grifa or Hachís. In the United Kingdom, it is variously known as brown (also a name for heroin in some parts of the UK), hash, resin, solid, and block. In the Netherlands, this is called Hasj or Assi (although coffee shops will maintain a wide variety of types, i.e.: Polm, Blond, Tempel Bol, Isolator, Zero-Zero or Waterwerks, generally relating to either the method of production, country of origin or type of marijuana used.). In Brazil, it is commonly called haxa. Also, there is a branch of nearly white powder hash (pollen or kief hash) that is the result of not stamping the raw material for the more common compressed hashish. Soft hash is usually dark brown to black in color and goes under the name black in France, squidgey or soft black (named due to the color and properties of the hash) in the UK. The very potent Paki Black is so named because it originates in Pakistan. Soft, dark hash in the Netherlands is normally referred to as Afghan. Common Kashmiri brands are Citral and Fungus. Hashish use is experiencing a resurgence in parts of North America (especially the Pacific Northwest) with the use and commercial availability of ice-water extraction kits.[citation needed] # Preparation and methods of use Like ordinary cannabis preparations, hashish is usually smoked, though it can also be eaten or vaporised. Hash is sometimes prepared for smoking by heating it with a flame for a couple of seconds, producing some bubbling or sizzling. It then softens and can be crumbled into tiny pieces or formed into shapes to obtain maximum surface area when burning. A sharp razor knife can be used to divide hard unheated hash into small slender pieces. If the material is of the right consistency, it can be ground up with a marijuana grinder. Although heating may cause more THC to be released in its active form. ## Vaporization Used with hashish as with any cannabis, tobacco or other herb material, a vaporizer can extract cannabinoids at a temperature of 350°F./150°C., protecting against loss of this ingredient which occurs in burning, and eliminating carbon monoxide and other combustion toxins. Since hashish is solid, it's surface area is enlarged by the user, for a maximum cannabinoid vaporization. ## "Knife Hits" Hash can be placed on very hot pieces of metal and the resulting vapor inhaled. "Knife hits" is a method that involves heating up knives on a stove, crushing a little ball of the hash between them and inhaling the released vapor through a tube or straw. Hash cones is a method where a piece of hash is attached to a pin or metal wire and then heated. ## One-hitter (semivaporizer) The next lowest temperature is achieved with a narrow-diameter, screened-crater utensil-- one-hitter, minitoke, kiseru or midwakh-- where the practiced user sucks the air slowly enough to assure slow, low-temperature burning, so that the cannabinol in any part of the hashish has time to vaporize from being heated by an already burning adjacent part of the hashish (semivaporizer). A butane lighter should be used instead of matches to permit frequent, very brief relightings, and a long tube (such as those found on hookahs) added giving the heated aerosol a longer distance to travel, i.e. more time to cool down before reaching the user's trachea. ## Dabous A piece of hash may be ignited by cigarette coals or other means and placed inside a container. The smoke that collects inside can then be inhaled. Dabous or Khabour, but most commonly "shi-sha" (glass in Arabic) is a North African technique. In Canada this technique is commonly referred to as "Bots" or "BTs" ("Bottle-Tokes"). ## Mixtures Often hash is mixed with tobacco, cannabis or another herb, and the combination rolled up into a cigarette or burned in a large pipe by users impatient to get it burning, a procedure best avoided as the high burning temperature results in major loss of THC (and the exposure to nicotine can result in tobacco addiction). Smoked by itself, hash usually creates a stronger psychoactive effect on the user.	https://www.wikidoc.org/index.php/Hashish
9e3034b68b378dc4ce05540d87df291699932630	wikidoc	Helipad	Helipad The word helipad is a blend meaning helicopter landing pad, a landing area for helicopters. Though helicopters can usually land anywhere flat, a fabricated helipad provides a clearly marked hard surface away from obstacles where a helicopter can land. Helipads are usually constructed out of concrete and are --LBiller 10:09, 21 May 2008 (EDT)marked with a circle and/or a letter "H", so as to be visible from the air. They may be located at a heliport or airport where fuel, air traffic control, and service facilities for aircraft are available. Usually a helipad does not have fuel and service facilities for aircraft, as does a heliport, and does not maintain a full time air traffic controller. Conversely, a helipad may also be located away from such facilities; for example, helipads are commonly placed on the roof of hospitals to facilitate MEDEVACs. Large ships sometimes have a helipad onboard, and some businesses maintain a helipad on the roof of their office tower. Helipads are not always constructed out of concrete; sometimes forest fire fighters will construct a temporary helipad out of wood to receive supplies in remote areas. Landing pads may also be constructed in extreme conditions like on frozen ice. The world's highest helipad, built by India, is located in the Siachen Glacier at a height of 21,000 feet above the sea level. Rooftop helipads sometimes display a large two-digit number, representing the weight limit (in thousands of pounds) of the pad. Retractable helipad systems are another type of landing surface that respond to a major problem in the helicopter travel sector. # Source Retractable Helipads Headland Retractable Landing Surfaces for Helicopters	Helipad The word helipad is a blend meaning helicopter landing pad, a landing area for helicopters. Though helicopters can usually land anywhere flat, a fabricated helipad provides a clearly marked hard surface away from obstacles where a helicopter can land. Helipads are usually constructed out of concrete and are --LBiller 10:09, 21 May 2008 (EDT)marked with a circle and/or a letter "H", so as to be visible from the air. They may be located at a heliport or airport where fuel, air traffic control, and service facilities for aircraft are available. Usually a helipad does not have fuel and service facilities for aircraft, as does a heliport, and does not maintain a full time air traffic controller. Conversely, a helipad may also be located away from such facilities; for example, helipads are commonly placed on the roof of hospitals to facilitate MEDEVACs. Large ships sometimes have a helipad onboard, and some businesses maintain a helipad on the roof of their office tower. Helipads are not always constructed out of concrete; sometimes forest fire fighters will construct a temporary helipad out of wood to receive supplies in remote areas. Landing pads may also be constructed in extreme conditions like on frozen ice. The world's highest helipad, built by India, is located in the Siachen Glacier at a height of 21,000 feet above the sea level. Rooftop helipads sometimes display a large two-digit number, representing the weight limit (in thousands of pounds) of the pad. Retractable helipad systems are another type of landing surface that respond to a major problem in the helicopter travel sector. # Source Retractable Helipads Headland Retractable Landing Surfaces for Helicopters	https://www.wikidoc.org/index.php/Helipad
acf08df0645f0a2e12da5c5dac05f002334a0700	wikidoc	Henbane	Henbane Henbane (Hyoscyamus niger), also known as Stinking Nightshade, is a plant of the family Solanaceae that originated in Eurasia, though it is now globally distributed. # Toxicity and Historical Usage It was historically used in combination with other plants, such as Mandrake, Deadly Nightshade, and Datura as an anaesthetic potion, as well as for its psychoactive properties in "magic brews." Its usage was originally in continental Europe and Asia, though it did spread to England sometime during the Middle Ages. The use of Henbane by the ancient Greeks was documented by Pliny. The plant, recorded as Herba Apollinaris, was used to yield oracles by the priestesses of Apollo. Henbane can be toxic in low doses. Its name came from Anglo-Saxon hennbana = "killer of hens". Hyoscyamine, scopolamine, and other tropane alkaloids have been found in the foliage and seeds of the plant. Common effects of henbane use in humans include hallucinations, dilated pupils, restlessness, and flushed skin. Less common symptoms such as tachycardia, convulsions, vomiting, hypertension, hyperpyrexia and ataxia have all been noted. Despite this it is used as a food plant by the larvae of some Lepidoptera species including Cabbage Moth. It was traditionally used in German pilsner beers as a flavouring, until the Bavarian Purity Law was passed in 1516 and outlawed the use of Henbane and allowed only the use of hops. Henbane or Hyoscyamus was also known to have been used as an anesthetic in the first Arab hospitals. In 1910, a well known British homeopathic doctor, Hawley Harvey Crippen, used henbane to kill his wife. Henbane is behind the etymology of the Czech town Plzeň and pilsener beer. # Citations - ↑ Jump up to: 1.0 1.1 1.2 1.3 1.4 1.5 1.6 Roberts 1998, p. 31.	Henbane Henbane (Hyoscyamus niger[1]), also known as Stinking Nightshade, is a plant of the family Solanaceae[1] that originated in Eurasia,[1] though it is now globally distributed. # Toxicity and Historical Usage It was historically used in combination with other plants, such as Mandrake, Deadly Nightshade, and Datura as an anaesthetic potion, as well as for its psychoactive properties in "magic brews."[1] Its usage was originally in continental Europe and Asia, though it did spread to England sometime during the Middle Ages. The use of Henbane by the ancient Greeks was documented by Pliny. The plant, recorded as Herba Apollinaris, was used to yield oracles by the priestesses of Apollo.[1] Henbane can be toxic in low doses. Its name came from Anglo-Saxon hennbana = "killer of hens". Hyoscyamine, scopolamine, and other tropane alkaloids have been found in the foliage and seeds of the plant.[1] Common effects of henbane use in humans include hallucinations,[1] dilated pupils, restlessness, and flushed skin. Less common symptoms such as tachycardia, convulsions, vomiting, hypertension, hyperpyrexia and ataxia have all been noted. Despite this it is used as a food plant by the larvae of some Lepidoptera species including Cabbage Moth. It was traditionally used in German pilsner beers as a flavouring, until the Bavarian Purity Law was passed in 1516 and outlawed the use of Henbane and allowed only the use of hops.[citation needed] Henbane or Hyoscyamus was also known to have been used as an anesthetic in the first Arab hospitals. In 1910, a well known British homeopathic doctor, Hawley Harvey Crippen, used henbane to kill his wife. Henbane is behind the etymology of the Czech town Plzeň and pilsener beer. # Citations - ↑ Jump up to: 1.0 1.1 1.2 1.3 1.4 1.5 1.6 Roberts 1998, p. 31.	https://www.wikidoc.org/index.php/Henbane

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