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id stringlengths 40 40	source stringclasses 9 values	title stringlengths 2 345	clean_text stringlengths 35 1.63M	raw_text stringlengths 4 1.63M	url stringlengths 4 498
3e3cada2987b3c344e072ccc7c83cccd82c1979f	wikidoc	PARD6A	PARD6A Partitioning defective 6 homolog alpha is a protein that in humans is encoded by the PARD6A gene. # Function This gene is a member of the PAR6 family and encodes a protein with a PSD95/Discs-large/ZO1 (PDZ) domain and a semi-Cdc42/Rac interactive binding (CRIB) domain. This cell membrane protein is involved in asymmetrical cell division and cell polarization processes as a member of a multi-protein complex. The protein also has a role in the epithelial-to-mesenchymal transition (EMT) that characterizes the invasive phenotype associated with metastatic carcinomas. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. A recent study shows that Par6 associates with PKC-ι but not with PKC-zeta in melanoma. Oncogenic PKC-iota can promote melanoma cell invasion by up-regulating PKC-ι/Par6 pathway during EMT. PKC-ι inhibition or knockdown resulted an increase E-cadherin and RhoA levels while decreasing total Vimentin, phophorylated Vimentin (S39) and Par6 in metastatic melanoma cells. These results suggested that PKC-ι is involved in signaling pathways which upregulate EMT in melanoma. # Interactions PARD6A has been shown to interact with: - CDC42, - ECT2 - Protein kinase Mζ, and - RAC1. - Protein kinase C-ι.	PARD6A Partitioning defective 6 homolog alpha is a protein that in humans is encoded by the PARD6A gene.[1][2][3] # Function This gene is a member of the PAR6 family and encodes a protein with a PSD95/Discs-large/ZO1 (PDZ) domain and a semi-Cdc42/Rac interactive binding (CRIB) domain. This cell membrane protein is involved in asymmetrical cell division and cell polarization processes as a member of a multi-protein complex. The protein also has a role in the epithelial-to-mesenchymal transition (EMT) that characterizes the invasive phenotype associated with metastatic carcinomas. Alternate transcriptional splice variants, encoding different isoforms, have been characterized.[3] A recent study shows that Par6 associates with PKC-ι but not with PKC-zeta in melanoma. Oncogenic PKC-iota can promote melanoma cell invasion by up-regulating PKC-ι/Par6 pathway during EMT. PKC-ι inhibition or knockdown resulted an increase E-cadherin and RhoA levels while decreasing total Vimentin, phophorylated Vimentin (S39) and Par6 in metastatic melanoma cells. These results suggested that PKC-ι is involved in signaling pathways which upregulate EMT in melanoma.[4] # Interactions PARD6A has been shown to interact with: - CDC42,[2][5][6] - ECT2[7] - Protein kinase Mζ,[2][7][8] and - RAC1.[2][6] - Protein kinase C-ι.[4]	https://www.wikidoc.org/index.php/PARD6A
ed1a95bf5f2960397b7a959f1c4dacbbfe724b3c	wikidoc	PCDH15	PCDH15 Protocadherin-15 is a protein that in humans is encoded by the PCDH15 gene. # Function This gene is a member of the cadherin superfamily. Family members encode integral membrane proteins that mediate calcium-dependent cell-cell adhesion. The protein product of this gene consists of a signal peptide, 11 extracellular calcium-binding domains, a transmembrane domain and a unique cytoplasmic domain. It plays an essential role in maintenance of normal retinal and cochlear function. It is thought to interact with CDH23 to form tip-link filaments. # Clinical significance Mutations in this gene have been associated with hearing loss, which is consistent with its location at the Usher syndrome type 1F (USH1F) critical region on chromosome 10. Variation within it has also been found to be associated with normal differences in human facial appearance.	PCDH15 Protocadherin-15 is a protein that in humans is encoded by the PCDH15 gene.[1][2][3] # Function This gene is a member of the cadherin superfamily. Family members encode integral membrane proteins that mediate calcium-dependent cell-cell adhesion. The protein product of this gene consists of a signal peptide, 11 extracellular calcium-binding domains, a transmembrane domain and a unique cytoplasmic domain. It plays an essential role in maintenance of normal retinal and cochlear function.[3] It is thought to interact with CDH23 to form tip-link filaments.[4] # Clinical significance Mutations in this gene have been associated with hearing loss, which is consistent with its location at the Usher syndrome type 1F (USH1F) critical region on chromosome 10.[3] Variation within it has also been found to be associated with normal differences in human facial appearance.[5]	https://www.wikidoc.org/index.php/PCDH15
796a0173f472fb88eaa06ac9338a1a57827c657e	wikidoc	PCDHA9	PCDHA9 Protocadherin alpha-9 is a protein that in humans is encoded by the PCDHA9 gene. This gene is a member of the protocadherin alpha gene cluster, one of three related gene clusters tandemly linked on chromosome 5 that demonstrate an unusual genomic organization similar to that of B-cell and T-cell receptor gene clusters. The alpha gene cluster is composed of 15 cadherin superfamily genes related to the mouse CNR genes and consists of 13 highly similar and 2 more distantly related coding sequences. The tandem array of 15 N-terminal exons, or variable exons, are followed by downstream C-terminal exons, or constant exons, which are shared by all genes in the cluster. The large, uninterrupted N-terminal exons each encode six cadherin ectodomains while the C-terminal exons encode the cytoplasmic domain. These neural cadherin-like cell adhesion proteins are integral plasma membrane proteins that most likely play a critical role in the establishment and function of specific cell-cell connections in the brain. Alternative splicing has been observed and additional variants have been suggested but their full-length nature has yet to be determined.	PCDHA9 Protocadherin alpha-9 is a protein that in humans is encoded by the PCDHA9 gene.[1][2] This gene is a member of the protocadherin alpha gene cluster, one of three related gene clusters tandemly linked on chromosome 5 that demonstrate an unusual genomic organization similar to that of B-cell and T-cell receptor gene clusters. The alpha gene cluster is composed of 15 cadherin superfamily genes related to the mouse CNR genes and consists of 13 highly similar and 2 more distantly related coding sequences. The tandem array of 15 N-terminal exons, or variable exons, are followed by downstream C-terminal exons, or constant exons, which are shared by all genes in the cluster. The large, uninterrupted N-terminal exons each encode six cadherin ectodomains while the C-terminal exons encode the cytoplasmic domain. These neural cadherin-like cell adhesion proteins are integral plasma membrane proteins that most likely play a critical role in the establishment and function of specific cell-cell connections in the brain. Alternative splicing has been observed and additional variants have been suggested but their full-length nature has yet to be determined.[2]	https://www.wikidoc.org/index.php/PCDHA9
24d8bb82fc693faae82ea78de38a162ff3380c3e	wikidoc	PDCD10	PDCD10 Programmed cell death protein 10 is a protein that in humans is encoded by the PDCD10 gene. # Function This gene encodes a protein, originally identified in a premyeloid cell line, with similarity to proteins that participate in apoptosis. Three alternative transcripts encoding the same protein, differing only in their 5' UTRs, have been identified for this gene. # Gene Loss of function mutations in PDCD10 result in the onset of Cerebral Cavernous Malformations (CCM) illness. Therefore, this gene is also called CCM3. Cerebral cavernous malformations (CCMs) are vascular malformations in the brain and spinal cord made of dilated capillary vessels. # Interactions CCM3 encodes a protein called Programmed Cell Death 10 (PDCD10). The function of this protein has only recently begun to be understood. PDCD10 has roles in vascular development and VEGF signaling1, apoptosis and functions as part of a larger signaling complex that includes germinal center kinase III,. Specifically, PDCD10 has been shown to interact with RP6-213H19.1, STK25, STRN, STRN3, MOBKL3, CTTNBP2NL, STK24 and FAM40A. # Model organisms Model organisms have been used in the study of PDCD10 function. A conditional knockout mouse line, called Pdcd10tm1a(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. Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion. Twenty five tests were carried out on mutant mice and two significant abnormalities were observed. No homozygous mutant embryos were identified during gestation, and therefore none survived until weaning. The remaining tests were carried out on heterozygous mutant adult mice; no additional significant abnormalities were observed in these animals.	PDCD10 Programmed cell death protein 10 is a protein that in humans is encoded by the PDCD10 gene.[1][2] # Function This gene encodes a protein, originally identified in a premyeloid cell line, with similarity to proteins that participate in apoptosis. Three alternative transcripts encoding the same protein, differing only in their 5' UTRs, have been identified for this gene.[2] # Gene Loss of function mutations in PDCD10 result in the onset of Cerebral Cavernous Malformations (CCM) illness.[1] Therefore, this gene is also called CCM3. Cerebral cavernous malformations (CCMs) are vascular malformations in the brain and spinal cord made of dilated capillary vessels. # Interactions CCM3 encodes a protein called Programmed Cell Death 10 (PDCD10). The function of this protein has only recently begun to be understood. PDCD10 has roles in vascular development and VEGF signaling1,[3] apoptosis[4] and functions as part of a larger signaling complex that includes germinal center kinase III,.[5][6] Specifically, PDCD10 has been shown to interact with RP6-213H19.1,[7] STK25,[7][8] STRN,[7] STRN3,[7] MOBKL3,[7] CTTNBP2NL,[7] STK24[7][8][9] and FAM40A.[7] # Model organisms Model organisms have been used in the study of PDCD10 function. A conditional knockout mouse line, called Pdcd10tm1a(KOMP)Wtsi[14][15] 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.[16][17][18] Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion.[12][19] Twenty five tests were carried out on mutant mice and two significant abnormalities were observed.[12] No homozygous mutant embryos were identified during gestation, and therefore none survived until weaning. The remaining tests were carried out on heterozygous mutant adult mice; no additional significant abnormalities were observed in these animals.[12]	https://www.wikidoc.org/index.php/PDCD10
d05ff6625567d084da18a75439bc4e095b7cf608	wikidoc	PDE10A	PDE10A cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A is an enzyme that in humans is encoded by the PDE10A gene. Various cellular responses are regulated by the second messengers cAMP and cGMP. Phosphodiesterases, such as PDE10A, eliminate cAMP- and cGMP-mediated intracellular signaling by hydrolyzing the cyclic nucleotide to the corresponding nucleoside 5-prime monophosphate. # Inhibitors - Compound 96: IC50 = 700 pM, high selectivity against all other members of the PDE family - Papaverine - PF-2545920 - TAK-063: IC50 = 300 pM - AMG 579 # Research Preliminary evidence indicates a possible link between PDE10A expression and obesity in mice and humans.	PDE10A cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A is an enzyme that in humans is encoded by the PDE10A gene.[1][2] Various cellular responses are regulated by the second messengers cAMP and cGMP. Phosphodiesterases, such as PDE10A, eliminate cAMP- and cGMP-mediated intracellular signaling by hydrolyzing the cyclic nucleotide to the corresponding nucleoside 5-prime monophosphate.[2][3] # Inhibitors - Compound 96: IC50 = 700 pM, high selectivity against all other members of the PDE family[4] - Papaverine[5] - PF-2545920[6] - TAK-063: IC50 = 300 pM[7] - AMG 579[8] # Research Preliminary evidence indicates a possible link between PDE10A expression and obesity in mice and humans.[9]	https://www.wikidoc.org/index.php/PDE10A
b039997709895225c9dad2dc0ad9e9b91a87affb	wikidoc	PDGFRB	PDGFRB Beta-type platelet-derived growth factor receptor is a protein that in humans is encoded by the PDGFRB gene. # Gene The PDGFRB gene is located on human chromosome 5 at position q32 (designated as 5q32) and contains 25 exons. The gene is flanked by the genes for granulocyte-macrophage colony-stimulating factor and Colony stimulating factor 1 receptor (also termed macrophage-colony stimulating factor receptor), all three of which may be lost together by a single deletional mutation thereby causing development of the 5q-syndrome. Other genetic abnormalities in PDGFRB lead to various forms of potentially malignant bone marrow disorders: small deletions in and chromosome translocations causing fusions between PDGFRB and anyone of at least 30 genes can cause Myeloproliferative neoplasms that commonly involve eosinophilia, eosinophil-induced organ injury, and possible progression to aggressive leukemia (see blow). # Structure The PDGFRB gene encodes a typical receptor tyrosine kinase, which is a transmembrane protein consisting of an extracellular ligand binding domain, a transmembrane domain and an intracellular tyrosine kinase domain. The molecular mass of the mature, glycosylated PDGFRβ protein is approximately 180 kDa. # Modes of activation Activation of PDGFRβ requires de-repression of the receptor's kinase activity. The ligand for PDGFRβ (PDGF) accomplishes this in the course of assembling a PDGFRβ dimer. Two of the five PDGF isoforms activate PDGFRβ (PDGF-B and PDGF-D). The activated receptor phosphorylates itself and other proteins, and thereby engages intracellular signaling pathways that trigger cellular responses such as migration and proliferation. There are also PDGF-independent modes of de-repressing the PDGFRβ's kinase activity and hence activating it. For instance, forcing PDGFRβ into close proximity of each other by overexpression or with antibodies directed against the extracellular domain. Alternatively, mutations in the kinase domain that stabilize a kinase active conformation result in constitutive activation. Unlike PDGFRα, PDGFRβ cannot be indirectly activated. This is because PDGFRβ recruits RasGAP and thereby attenuates Ras/PI3K activity, which is required to engage a feed-forward loop that is responsible for this mode of activation. # Role in physiology/pathology The phenotype of knock out mice demonstrates that pdgfrb is essential for vascular development, and that pdgfb is responsible for activating PDGFRβ during embryogenesis. Eliminating either PDGFRB, or PDGF-B reduces the number of pericytes and vascular smooth muscle cells, and thereby compromises the integrity and/or functionality of the vasculature in multiple organs, including the brain, heart, kidney, skin and eye. In vitro studies using cultured cells indicate that endothelial cells secrete PDGF, which recruits PDGFRβ-expressing pericytes that stabilize nascent blood vessels. Mice harboring a single activated allele of pdgfrb show a number of postnatal phenotypes including reduced differentiation of aortic vascular smooth muscle cells and brain pericytes. Similarly, differentiation of adipose from pericytes and mesenchymal cells is suppressed. Misregulation of the PDGFRβ's kinase activity (typically activation) contributes to endemic diseases such as cancer and cardiovascular disease. ## PDGFRB mutations ### 5q- Syndrome Human chromosome 5 deletions that remove three adjacent genes, those for granulocyte-macrophage colony-stimulating factor, PDGFRB, and Colony stimulating factor 1 receptor, cause the Chromosome 5q deletion syndrome (5q- syndrome). This syndrome is a unique type of myelodysplastic syndrome characterized by a prolonged disease course, a low rate of transformation to an aggressive form of leukemia, and an anemia which in many patients is profound, refractory to traditional therapies (e.g. iron supplements, Erythropoietin), and requiring maintenance red blood cell transfusions. The disease is treated with a chemotherapy drug, lenalidomide. ### PDGFRB Translocations Human chromosome translocations between the PDGFRB gene and at least any one of 30 genes on other chromosomes lead to myeloid and/or lymphoid neoplasms that are many ways similar to the neoplasm caused by the fusion of the PDGFRA (i.e. platelet derived growth factor receptor A or alpha-type-platelet derived growth factor receptor) gene with the FIP1L1 gene (see FIP1L1-PDGFRA fusion gene. The most common of these rare mutations is the translocation of PDGFRB gene with the ETV6 gene (also termed ETS variant gene 6). The ETV6 gene codes for a transcription factor protein that in mice appears to be required for hematopoiesis and maintenance of the developing vascular network. The gene is located on human chromosome 12 at the p13 position, consists of 14 exons, and is well-known to be involved in a large number of chromosomal rearrangements associated with leukemia and congenital fibrosarcoma. Translocations between it and the PDGFRB gene, notated as t(5;12)(q33;p13), yield a PDGFRB-ETV6 fused gene that encodes a fusion protein, PDGFRB-ETV6. This chimeric protein, unlike the PDGFRB protein: a) has continuously active PDGFRB-mediated tyrosine kinase due to its forced dimerization by the PNT protein binding domain of the ETV6 protein; b) is highly stable due to its resistance to ubiquitin-Proteasome degradation; and c) therefore over-stimulates cell signaling pathways such as STAT5, NF-κB, and Extracellular signal–regulated kinases which promote cell growth and proliferation. This continuous signaling, it is presumed, leads to the development of myeloid and/or lymphoid neoplasms that commonly include increased numbers of blood born and tissue eosinophils, eosinophil-induced organ and tissue injury, and possible progression to aggressive form of leukemia. PDGFRB-ETV6 fusion protein-induced neoplasms often present with features that would classify them as Chronic myelomonocytic leukemias, juvenile myelomonocytic leukemia, Atypical or Philadelphia chromosome negative chronic myeloid leukemias, myelodysplastic syndromes, acute myelogenous leukemias, or acute lymphoblastic leukemias. The disease is now classified by the World Health Organization as one form of clonal eosinophilia. It is critical that the PDGFRB-ETV6 fusion protein-driven disease be diagnostically distinguished from many of the just cited other diseases because of its very different treatment. Patients with the PDGFRB-ETV6 fusion protein-driven disease are more often adult males but rarely children. They present with anemia, increases in blood eosinophils and monocytes, splenomegaly, and, less often, lymphadenopathy. Bone marrow examination may reveal cellular features similar to that seen in the aforementioned diseases. Diagnosis is may by conventional cytogenetic examination of blood or bone marrow cells to test for PDGFRB rearrangements using Fluorescence in situ hybridization or to test for the fused FDGFRB-ATV6 fluorescence in situ hybridization and/or Real-time polymerase chain reaction using appropriate nucleotide probes. These patients, unlike many patients with similarly appearing neoplasms, respond well to the tyrosine kinase inhibitor, imatinib. The drug often causes long-term complete hematological and cytogenic remissions as doses well below those used to treat chronic myelogenous leukemia. Primary or acquired drug resistance to this drug is very rare. Additional adjuvant chemotherapy may be necessary if a patients disease is unresponsive to tyrosine kinase inhibitor therapy and/or progresses to more aggressive disease phase similar to that seen in the blast crisis of chronic myelogenous leukemia. The PDGFRB gene has been found to fuse with at least 36 other genes to form fusion genes that encode chimeric proteins that are known or presumed to possess: a) continuously active PDGFRB-derived tyrosine kinase activity; b) the ability to continuously stimulate the growth and proliferation of hematological stem cells; and c) the ability to cause myeloid and lymphoid neoplasms that commonly but not always are associated with eosinophilia. In all instances, these gene fusion diseases are considered types of clonal eosinophilia with recommended treatment regimens very different than those of similar hematological malignancies. The genes fusing to PDGFRB, their chromosomal location, and the notations describing their fused genes are given in the following table. Similar to PDGFRB-ETV6 translocations, these translocations are generally in-frame and encode for fusion proteins with their PDGFRB-derived tyrosine kinase being continuously active and responsible for causing the potentially malignant growth of its myeloid and/or lymphoid harboring cells. Patients are usually middle-aged men. They commonly present with anemia, eosinophilia, monocytosis, and splenomegaly and have their disease classified as chronic myelomonocytic leukemia, atypical chronic myelomonocytic leukemia, juvenile myelomonocytic leukemia, myelodysplastic syndrome, acute myelogenous leukemia, acute lymphoblastic leukemia, or T lymphoblastic lymphoma. Diganosis relies on cytogenetic analyses to detect breakpoints in the long arm of chromosome 5 by Fluorescence in situ hybridization. These patients usually respond well to imatinib therapy. Primary familial brain calcification (see Fahr's syndrome) is a rare disease involving bilateral calcifications in the brain, predominantly in basal ganglia but also cerebellum, thalamus, and brainstem in patients presenting with diverse neurologic (e.g. movement disorders, parkinsonism, seizures, headache) features and psychiatric (e.g. cognitive impairment, mood disorders, psychotic symptoms, and obsessive-compulsive) disturbances. In a minority of cases, the disease is associated with apparent autosomal dominant loss of function mutations in PDGFRB or the gene which encodes a ligand that simulates PDGFRB, Platelet-derived growth factor, PDGFB. PDGFRB is extensively expressed in the neurons, chorioid plexus, vascular smooth muscle cells, and pericytes of the human brain, particularly the basal ganglia and the dentate nucleus. It is proposed that signal transduction through PDGFRB maintains blood–brain barrier integrity and that loss of the PDGFRB receptor or is ligand, PDGFB, disrupts the blood–brain barrier, subsequently promoting (peri)vascular calcium deposition and thereby causing the dysfunction and death of neurons. # Interactions PDGFRB has been shown to interact with: - CRK, - Caveolin 1, - Grb2, - NCK1, - NCK2, - PDGFR-α, - PTPN11, - RAS p21 protein activator 1, - SHC1 and - Sodium-hydrogen antiporter 3 regulator 1.	PDGFRB Beta-type platelet-derived growth factor receptor is a protein that in humans is encoded by the PDGFRB gene. # Gene The PDGFRB gene is located on human chromosome 5 at position q32 (designated as 5q32) and contains 25 exons. The gene is flanked by the genes for granulocyte-macrophage colony-stimulating factor and Colony stimulating factor 1 receptor (also termed macrophage-colony stimulating factor receptor), all three of which may be lost together by a single deletional mutation thereby causing development of the 5q-syndrome.[1] Other genetic abnormalities in PDGFRB lead to various forms of potentially malignant bone marrow disorders: small deletions in and chromosome translocations causing fusions between PDGFRB and anyone of at least 30 genes can cause Myeloproliferative neoplasms that commonly involve eosinophilia, eosinophil-induced organ injury, and possible progression to aggressive leukemia (see blow).[2] # Structure The PDGFRB gene encodes a typical receptor tyrosine kinase, which is a transmembrane protein consisting of an extracellular ligand binding domain, a transmembrane domain and an intracellular tyrosine kinase domain. The molecular mass of the mature, glycosylated PDGFRβ protein is approximately 180 kDa. # Modes of activation Activation of PDGFRβ requires de-repression of the receptor's kinase activity. The ligand for PDGFRβ (PDGF) accomplishes this in the course of assembling a PDGFRβ dimer. Two of the five PDGF isoforms activate PDGFRβ (PDGF-B and PDGF-D). The activated receptor phosphorylates itself and other proteins, and thereby engages intracellular signaling pathways that trigger cellular responses such as migration and proliferation. There are also PDGF-independent modes of de-repressing the PDGFRβ's kinase activity and hence activating it. For instance, forcing PDGFRβ into close proximity of each other by overexpression or with antibodies directed against the extracellular domain. Alternatively, mutations in the kinase domain that stabilize a kinase active conformation result in constitutive activation. Unlike PDGFRα, PDGFRβ cannot be indirectly activated. This is because PDGFRβ recruits RasGAP and thereby attenuates Ras/PI3K activity, which is required to engage a feed-forward loop that is responsible for this mode of activation.[3][4] # Role in physiology/pathology The phenotype of knock out mice demonstrates that pdgfrb is essential for vascular development, and that pdgfb is responsible for activating PDGFRβ during embryogenesis. Eliminating either PDGFRB, or PDGF-B reduces the number of pericytes and vascular smooth muscle cells, and thereby compromises the integrity and/or functionality of the vasculature in multiple organs, including the brain, heart, kidney, skin and eye.[5][6][7][8] In vitro studies using cultured cells indicate that endothelial cells secrete PDGF, which recruits PDGFRβ-expressing pericytes that stabilize nascent blood vessels.[9] Mice harboring a single activated allele of pdgfrb show a number of postnatal phenotypes including reduced differentiation of aortic vascular smooth muscle cells and brain pericytes. Similarly, differentiation of adipose from pericytes and mesenchymal cells is suppressed.[10] Misregulation of the PDGFRβ's kinase activity (typically activation) contributes to endemic diseases such as cancer and cardiovascular disease.[11][12][13] ## PDGFRB mutations ### 5q- Syndrome Human chromosome 5 deletions that remove three adjacent genes, those for granulocyte-macrophage colony-stimulating factor, PDGFRB, and Colony stimulating factor 1 receptor, cause the Chromosome 5q deletion syndrome (5q- syndrome). This syndrome is a unique type of myelodysplastic syndrome characterized by a prolonged disease course, a low rate of transformation to an aggressive form of leukemia, and an anemia which in many patients is profound, refractory to traditional therapies (e.g. iron supplements, Erythropoietin), and requiring maintenance red blood cell transfusions. The disease is treated with a chemotherapy drug, lenalidomide.[1][14] ### PDGFRB Translocations Human chromosome translocations between the PDGFRB gene and at least any one of 30 genes on other chromosomes lead to myeloid and/or lymphoid neoplasms that are many ways similar to the neoplasm caused by the fusion of the PDGFRA (i.e. platelet derived growth factor receptor A or alpha-type-platelet derived growth factor receptor) gene with the FIP1L1 gene (see FIP1L1-PDGFRA fusion gene. The most common of these rare mutations is the translocation of PDGFRB gene with the ETV6 gene (also termed ETS variant gene 6). The ETV6 gene codes for a transcription factor protein that in mice appears to be required for hematopoiesis and maintenance of the developing vascular network. The gene is located on human chromosome 12 at the p13 position, consists of 14 exons, and is well-known to be involved in a large number of chromosomal rearrangements associated with leukemia and congenital fibrosarcoma.[15] Translocations between it and the PDGFRB gene, notated as t(5;12)(q33;p13), yield a PDGFRB-ETV6 fused gene that encodes a fusion protein, PDGFRB-ETV6. This chimeric protein, unlike the PDGFRB protein: a) has continuously active PDGFRB-mediated tyrosine kinase due to its forced dimerization by the PNT protein binding domain of the ETV6 protein; b) is highly stable due to its resistance to ubiquitin-Proteasome degradation; and c) therefore over-stimulates cell signaling pathways such as STAT5, NF-κB, and Extracellular signal–regulated kinases which promote cell growth and proliferation. This continuous signaling, it is presumed, leads to the development of myeloid and/or lymphoid neoplasms that commonly include increased numbers of blood born and tissue eosinophils, eosinophil-induced organ and tissue injury, and possible progression to aggressive form of leukemia.[16] PDGFRB-ETV6 fusion protein-induced neoplasms often present with features that would classify them as Chronic myelomonocytic leukemias, juvenile myelomonocytic leukemia, Atypical or Philadelphia chromosome negative chronic myeloid leukemias, myelodysplastic syndromes, acute myelogenous leukemias, or acute lymphoblastic leukemias. The disease is now classified by the World Health Organization as one form of clonal eosinophilia.[17] It is critical that the PDGFRB-ETV6 fusion protein-driven disease be diagnostically distinguished from many of the just cited other diseases because of its very different treatment. Patients with the PDGFRB-ETV6 fusion protein-driven disease are more often adult males but rarely children. They present with anemia, increases in blood eosinophils and monocytes, splenomegaly, and, less often, lymphadenopathy. Bone marrow examination may reveal cellular features similar to that seen in the aforementioned diseases. Diagnosis is may by conventional cytogenetic examination of blood or bone marrow cells to test for PDGFRB rearrangements using Fluorescence in situ hybridization or to test for the fused FDGFRB-ATV6 fluorescence in situ hybridization and/or Real-time polymerase chain reaction using appropriate nucleotide probes.[16] These patients, unlike many patients with similarly appearing neoplasms, respond well to the tyrosine kinase inhibitor, imatinib. The drug often causes long-term complete hematological and cytogenic remissions as doses well below those used to treat chronic myelogenous leukemia. Primary or acquired drug resistance to this drug is very rare. Additional adjuvant chemotherapy may be necessary if a patients disease is unresponsive to tyrosine kinase inhibitor therapy and/or progresses to more aggressive disease phase similar to that seen in the blast crisis of chronic myelogenous leukemia.[16][2] The PDGFRB gene has been found to fuse with at least 36 other genes to form fusion genes that encode chimeric proteins that are known or presumed to possess: a) continuously active PDGFRB-derived tyrosine kinase activity; b) the ability to continuously stimulate the growth and proliferation of hematological stem cells; and c) the ability to cause myeloid and lymphoid neoplasms that commonly but not always are associated with eosinophilia. In all instances, these gene fusion diseases are considered types of clonal eosinophilia with recommended treatment regimens very different than those of similar hematological malignancies. The genes fusing to PDGFRB, their chromosomal location, and the notations describing their fused genes are given in the following table.[2][16] Similar to PDGFRB-ETV6 translocations, these translocations are generally in-frame and encode for fusion proteins with their PDGFRB-derived tyrosine kinase being continuously active and responsible for causing the potentially malignant growth of its myeloid and/or lymphoid harboring cells. Patients are usually middle-aged men. They commonly present with anemia, eosinophilia, monocytosis, and splenomegaly and have their disease classified as chronic myelomonocytic leukemia, atypical chronic myelomonocytic leukemia, juvenile myelomonocytic leukemia, myelodysplastic syndrome, acute myelogenous leukemia, acute lymphoblastic leukemia, or T lymphoblastic lymphoma. Diganosis relies on cytogenetic analyses to detect breakpoints in the long arm of chromosome 5 by Fluorescence in situ hybridization. These patients usually respond well to imatinib therapy.[2][16][27] Primary familial brain calcification (see Fahr's syndrome) is a rare disease involving bilateral calcifications in the brain, predominantly in basal ganglia but also cerebellum, thalamus, and brainstem in patients presenting with diverse neurologic (e.g. movement disorders, parkinsonism, seizures, headache) features and psychiatric (e.g. cognitive impairment, mood disorders, psychotic symptoms, and obsessive-compulsive) disturbances. In a minority of cases, the disease is associated with apparent autosomal dominant loss of function mutations in PDGFRB or the gene which encodes a ligand that simulates PDGFRB, Platelet-derived growth factor, PDGFB. PDGFRB is extensively expressed in the neurons, chorioid plexus, vascular smooth muscle cells, and pericytes of the human brain, particularly the basal ganglia and the dentate nucleus. It is proposed that signal transduction through PDGFRB maintains blood–brain barrier integrity and that loss of the PDGFRB receptor or is ligand, PDGFB, disrupts the blood–brain barrier, subsequently promoting (peri)vascular calcium deposition and thereby causing the dysfunction and death of neurons.[28][29] # Interactions PDGFRB has been shown to interact with: - CRK,[30] - Caveolin 1,[31] - Grb2,[32][33][34] - NCK1,[32][35] - NCK2,[32][36][37] - PDGFR-α,[38][39] - PTPN11,[40][41] - RAS p21 protein activator 1,[42][43] - SHC1[44] and - Sodium-hydrogen antiporter 3 regulator 1.[45]	https://www.wikidoc.org/index.php/PDGFRB
50be0186b6fbaea2d92421638941ede44a0fdf08	wikidoc	PDLIM3	PDLIM3 Actin-associated LIM protein (ALP), also known as PDZ and LIM domain protein 3 is a protein that in humans is encoded by the PDLIM3 gene. ALP is highly expressed in cardiac and skeletal muscle, where it localizes to Z-discs and intercalated discs. ALP functions to enhance the crosslinking of actin by alpha actinin-2 and also appears to be essential for right ventricular chamber formation and contractile function. # Structure ALP exists primarily as two alternatively spliced variants; a 39.2 kDa (364 amino acids) protein in skeletal muscle and a 34.3 kDa (316 amino acids) protein in cardiac muscle and smooth muscle. ALP has a N-terminal PDZ domain and a C-terminal LIM domain. In addition, the ALP subfamily contains a specific 34 amino acid domain named the ALP-like motif, containing protein kinase C consensus sequences. The PDZ domain of ALP binds to alpha actinin-2, specifically to its spectrin-like repeats. The PDZ domain is a motif composed of 80-120 amino acids with conserved four residue GLGF sequences that typically interact with C-termini of cytoskeletal proteins. The region of heterogeneity in the two isoforms is between the PDZ domain and LIM domain. ALP is localized to chromosome 4q35. It has been shown that deletion of muscleblind-like 1 in mice can alter the splicing pattern of PDLIM3. # Function Studies have shown that ALP is present at the first stage of myofibrilogenesis where it is bound to alpha actinin-2, and this association remains intact in mature myofibrils where ALP is localized to Z-discs and intercalated discs. Alpha actinin-2 is however not required for targeting ALP to Z-lines. Studies in ALP knockout mice have shown that ALP facilitates the cross-linking of actin filaments by alpha actinin-2, and absence of ALP induces abnormal right ventricular chamber formation, dysplasia and cardiomyopathy. Further studies using right ventricular epicardial systolic strain and geometric remodeling analysis in these animals unveiled that absence of ALP diminishes right ventricular contractile function and alters the pattern of cardiac hypertrophic remodeling. Two studies using integrative genomic approaches to investigate genetic modifiers of collagen deposition or intrinsic aerobic running capacity (ARC) have mapped PDLIM3 to respective quantitative trait loci, suggesting that ALP may be involved in molecular networks related to these cardiac phenomena. # Clinical significance Chromosome 4 pericentric inversion has been observed in 10 patients, with associated cardiac defects linked to terminal 4q35.1 deletions, which may affect PDLIM3. # Interactions ALP interacts with: - alpha actinin-2 - beta-catenin	PDLIM3 Actin-associated LIM protein (ALP), also known as PDZ and LIM domain protein 3 is a protein that in humans is encoded by the PDLIM3 gene.[1][2][3] ALP is highly expressed in cardiac and skeletal muscle, where it localizes to Z-discs and intercalated discs. ALP functions to enhance the crosslinking of actin by alpha actinin-2 and also appears to be essential for right ventricular chamber formation and contractile function. # Structure ALP exists primarily as two alternatively spliced variants; a 39.2 kDa (364 amino acids) protein in skeletal muscle and a 34.3 kDa (316 amino acids) protein in cardiac muscle and smooth muscle.[4][5][6] ALP has a N-terminal PDZ domain and a C-terminal LIM domain. In addition, the ALP subfamily contains a specific 34 amino acid domain named the ALP-like motif, containing protein kinase C consensus sequences.[7] The PDZ domain of ALP binds to alpha actinin-2, specifically to its spectrin-like repeats.[8] The PDZ domain is a motif composed of 80-120 amino acids with conserved four residue GLGF sequences that typically interact with C-termini of cytoskeletal proteins.[9] The region of heterogeneity in the two isoforms is between the PDZ domain and LIM domain.[6] ALP is localized to chromosome 4q35.[8] It has been shown that deletion of muscleblind-like 1 in mice can alter the splicing pattern of PDLIM3.[10] # Function Studies have shown that ALP is present at the first stage of myofibrilogenesis where it is bound to alpha actinin-2, and this association remains intact in mature myofibrils where ALP is localized to Z-discs and intercalated discs. Alpha actinin-2 is however not required for targeting ALP to Z-lines.[11] Studies in ALP knockout mice have shown that ALP facilitates the cross-linking of actin filaments by alpha actinin-2, and absence of ALP induces abnormal right ventricular chamber formation, dysplasia and cardiomyopathy.[12] Further studies using right ventricular epicardial systolic strain and geometric remodeling analysis in these animals unveiled that absence of ALP diminishes right ventricular contractile function and alters the pattern of cardiac hypertrophic remodeling.[13] Two studies using integrative genomic approaches to investigate genetic modifiers of collagen deposition[14] or intrinsic aerobic running capacity (ARC)[15] have mapped PDLIM3 to respective quantitative trait loci, suggesting that ALP may be involved in molecular networks related to these cardiac phenomena. # Clinical significance Chromosome 4 pericentric inversion has been observed in 10 patients, with associated cardiac defects linked to terminal 4q35.1 deletions, which may affect PDLIM3.[16] # Interactions ALP interacts with: - alpha actinin-2[8] - beta-catenin[12]	https://www.wikidoc.org/index.php/PDLIM3
a6a07f3c23090e5446ee3919bcdddc7ce4b5a6cc	wikidoc	PEComa	PEComa - Synonyms and keywords:Perivascular epithelioid cell tumor # Overview The World Health Organization defines perivascular epithelioid cell tumors (PEComas) as mesenchymal tumors composed of histologically and immunohistochemically distinctive perivascular epithelioid cells (PECs). PEComas were first discovered by Pea and Colleagues in 1991. Zamboni et al in 1996 suggested the name PEComa for these neoplasms. They are a group of tumors that includes: angiomyolipoma (AML), lymphangioleiomyomatosis (LAM), and others. PEC has no normal counterpart, it expresses myogenic and melanocytes markers such as HMB45 and actin. Genetically they are linked to the tuberous sclerosis genes 1 and 2. There are no established risk factors for the PEComas but the risk increases in patients with tuberous sclerosis. The symptoms depend upon the area involved and can include palpable abdominal mass/abnormal vaginal bleeding (uterus), flank pain (kidney), or dull abdominal pain in the right upper quadrant (liver). It may occur in any age group, but median age is 54 years and is more common in females. Clinically, most PEComas are benign. CT scan and presence of PECs on histology are helpful in diagnosis. Surgery is the mainstay of treatment; however, other chemotherapeutic and immunotherapeutic drugs are under investigation. # Historical Perspective - In 1991, Pea et al first discovered PEComas, where they noticed these unusual cells in both angiomyolipoma (AML) and clear cell sugar tumor of lung (CCST). - In 1992, Bonetti et al proposed a cellular link between AML, clear cell sugar tumor (CCST), and lymphangioleiomyomatosis (LAM). They also associated these conditions with tuberous sclerosis complex (TSC) and advanced the concept of a family of neoplasms composed of these distinctive cells which were immunoreactive with melanocytes markers and exhibit and epitheloid appearance, a clear acidophilic cytoplasm and a perivascular distribution. - In 1996, Zamboni et al reported the first case of pancreatic CCST and suggested the name PEComa for these neoplasms composed of a pure proliferation of perivascular epithlioid cells (PECs). # Classification - The World Health Organization defines perivascular epithelioid cell tumors (PEComas) as "mesenchymal tumors composed of histologically and immunohistochemically distinctive perivascular epithelioid cells (PECs)". - There is no established system for the classification of PEComas because of the rarity of disease, but the PEComas are a group of tumors that includes following: Angiomyolipoma (AML) Clear cell sugar tumor of lung (CCST) Lymphangioleiomyomatosis (LAM) PEComas Not Otherwise Specified (PEComas-NOS); which includes: Clear cell myomelanocytic tumor of falciform ligament/ligamentum teres Abdominopelvic sarcoma of perivascular epithelioid cells Primary extrapulmonary clear cell sugar tumor - Angiomyolipoma (AML) - Clear cell sugar tumor of lung (CCST) - Lymphangioleiomyomatosis (LAM) - PEComas Not Otherwise Specified (PEComas-NOS); which includes: Clear cell myomelanocytic tumor of falciform ligament/ligamentum teres Abdominopelvic sarcoma of perivascular epithelioid cells Primary extrapulmonary clear cell sugar tumor - Clear cell myomelanocytic tumor of falciform ligament/ligamentum teres - Abdominopelvic sarcoma of perivascular epithelioid cells - Primary extrapulmonary clear cell sugar tumor - Folpe and Colleagues suggested criteria for malignancy based of following three criteria: Size greater than 8.0 cm Mitotic count of 1/50 high power field (HPF) Necrosis - Size greater than 8.0 cm - Mitotic count of 1/50 high power field (HPF) - Necrosis # Pathophysiology - Perivascular epithlioid cell (PEC) is a cell type constantly present in a group of tumors called PEComas. It has no normal counterpart. - PEC expresses myogenic and melanocytic markers such as HMB45 and actin. ## Microscopic Pathology - Perivascular epithlioid cells (PECs) are perivascular epithelioid cells with a clear/granular cytoplasm and round, oval, centrally located nucleus without prominent nucleoli. They have mild to any atypia. - On ultrastructural analysis, PEC contains microfilament bundles with electron dense condensation, numerous mitochondria and membrane bound dense granules. ## Genetics - The precursor cell of PEComas is currently unknown. Genetically, PECs are linked to the tuberous sclerosis genes TSC1 and TSC2. # Causes - PEComas are cause by genetic factors. Mutations in the tuberous sclerosis genes TSC1 and TSC2 has been associated. # Differentiating PEComa from other Diseases - PEComas must be differentiated from: Epithelioid smooth muscle cell tumors(epithelioid leiomyosarcoma and epithelioid leiomyoma) Malignant Melanoma Clear cell sarcoma of tendon and aponeurosis(melanoma of soft parts) Alveolar soft part sarcoma endometrial stromal sarcoma with clear cell features Carcinoma (especially renal cell and adrenocortical carcinoma) Paraganglioma Any other tumor with focal or prominent clear cell change - Epithelioid smooth muscle cell tumors(epithelioid leiomyosarcoma and epithelioid leiomyoma) - Malignant Melanoma - Clear cell sarcoma of tendon and aponeurosis(melanoma of soft parts) - Alveolar soft part sarcoma - endometrial stromal sarcoma with clear cell features - Carcinoma (especially renal cell and adrenocortical carcinoma) - Paraganglioma - Any other tumor with focal or prominent clear cell change # Epidemiology and Demographics - Patients of all age groups may develop PEComas, but the mean age at diagnosis is 54 years. - Women are more commonly affected by PEComas than men. # Risk Factors - There are no established risk factors for PEComas, but the risk increases in patients with tuberous sclerosis as the PECs are associated with TSC1 and TSC2 genes. # Screening - There is insufficient evidence to recommend routine screening for PEComas. # Natural History, Complications, and Prognosis - Clinically, most PEComas follow a benign course. - Malignant PEComas are also reported, many originating in the uterus and others arising in the prostate, jejunum, pelvis, broad ligament and somatic soft tissue. - They can metastasize distally to liver, lungs, intestines, bone and lymph nodes # Diagnosis ## Diagnostic Study of Choice - There are no established criteria for the diagnosis of PEComas. ## History and Symptoms - The symptoms of PEComa depend on the area involved: Palpable abdominal masses or abnormal vaginal bleeding (uterus) Flank pain (kidneys) Dull abdominal pain in right upper quadrant (liver) - Palpable abdominal masses or abnormal vaginal bleeding (uterus) - Flank pain (kidneys) - Dull abdominal pain in right upper quadrant (liver) ## Physical Examination - There are no any specific physical examination findings related to the PEComas. ## Laboratory findings ### Immunohistochemical markers - PECs typically stain for melanocytic markers (HMB-45, HMSA-1, Melan A (Mart 1), microophthalmia transcription factor (Mitf), myogenic markers (actin), and less commonly desmin. - Immunoreactivity for vimentin is unclear. ## Electrocardiogram - There are no ECG findings associated with PEComas. ## X-ray - There are no x-ray findings associated with PEComas. ## Echocardiography or Ultrasound - There are no echocardiography/ultrasound findings associated with PEComas. ## CT scan - CT scan may be helpful in the diagnosis of PEComas. Findings on CT scan suggestive of PEComas include: - Hypodense (15-50 hours field units) partially solid and partially cystic tumor with moderate contrast uptake (in kidney). Hypervascular tumor with delayed washout pattern in portal venous phase (in liver). Mass with no other pathology (in uterus). - Hypodense (15-50 hours field units) partially solid and partially cystic tumor with moderate contrast uptake (in kidney). - Hypervascular tumor with delayed washout pattern in portal venous phase (in liver). - Mass with no other pathology (in uterus). ## MRI - There are no MRI findings associated with PEComas. ## Other Imaging Findings - There are no other imaging findings associated with PEComas. ## Other Diagnostic Studies - There are no other diagnostic studies associated with PEComas. # Treatment ## Medical Therapy - There is no established medical therapy for PEComas. - Following chemotherapeutic and immunotherapeutic drugs have been tried with mixed results: Dacarbazine Doxorubicin Vincristine Imatinib mesylate Interferon alpha-b2 - Dacarbazine - Doxorubicin - Vincristine - Imatinib mesylate - Interferon alpha-b2 ## Surgery - Surgery is the mainstay of treatment for PEComas, as well as for local recurrences and metastasis, with the aim of obtaining clear resection margins. ## Primary Prevention - There are no established measures for the primary prevention of PEComas. ## Secondary Prevention - There are no established measures for the secondary prevention of PEComas.	PEComa Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Shyam Patel [2] Associate Editor(s)-in-Chief: Zahir Ali Shaikh, MD[3] - Synonyms and keywords:Perivascular epithelioid cell tumor # Overview The World Health Organization defines perivascular epithelioid cell tumors (PEComas) as mesenchymal tumors composed of histologically and immunohistochemically distinctive perivascular epithelioid cells (PECs). PEComas were first discovered by Pea and Colleagues in 1991. Zamboni et al in 1996 suggested the name PEComa for these neoplasms. They are a group of tumors that includes: angiomyolipoma (AML), lymphangioleiomyomatosis (LAM), and others. PEC has no normal counterpart, it expresses myogenic and melanocytes markers such as HMB45 and actin. Genetically they are linked to the tuberous sclerosis genes 1 and 2. There are no established risk factors for the PEComas but the risk increases in patients with tuberous sclerosis. The symptoms depend upon the area involved and can include palpable abdominal mass/abnormal vaginal bleeding (uterus), flank pain (kidney), or dull abdominal pain in the right upper quadrant (liver). It may occur in any age group, but median age is 54 years and is more common in females. Clinically, most PEComas are benign. CT scan and presence of PECs on histology are helpful in diagnosis. Surgery is the mainstay of treatment; however, other chemotherapeutic and immunotherapeutic drugs are under investigation. # Historical Perspective - In 1991, Pea et al first discovered PEComas, where they noticed these unusual cells in both angiomyolipoma (AML) and clear cell sugar tumor of lung (CCST).[1] - In 1992, Bonetti et al proposed a cellular link between AML, clear cell sugar tumor (CCST), and lymphangioleiomyomatosis (LAM). They also associated these conditions with tuberous sclerosis complex (TSC) and advanced the concept of a family of neoplasms composed of these distinctive cells which were immunoreactive with melanocytes markers and exhibit and epitheloid appearance, a clear acidophilic cytoplasm and a perivascular distribution.[2] - In 1996, Zamboni et al reported the first case of pancreatic CCST and suggested the name PEComa for these neoplasms composed of a pure proliferation of perivascular epithlioid cells (PECs).[3] # Classification - The World Health Organization defines perivascular epithelioid cell tumors (PEComas) as "mesenchymal tumors composed of histologically and immunohistochemically distinctive perivascular epithelioid cells (PECs)".[4] - There is no established system for the classification of PEComas because of the rarity of disease, but the PEComas are a group of tumors that includes following:[5] Angiomyolipoma (AML) Clear cell sugar tumor of lung (CCST) Lymphangioleiomyomatosis (LAM) PEComas Not Otherwise Specified (PEComas-NOS); which includes: Clear cell myomelanocytic tumor of falciform ligament/ligamentum teres Abdominopelvic sarcoma of perivascular epithelioid cells Primary extrapulmonary clear cell sugar tumor - Angiomyolipoma (AML) - Clear cell sugar tumor of lung (CCST) - Lymphangioleiomyomatosis (LAM) - PEComas Not Otherwise Specified (PEComas-NOS); which includes: Clear cell myomelanocytic tumor of falciform ligament/ligamentum teres Abdominopelvic sarcoma of perivascular epithelioid cells Primary extrapulmonary clear cell sugar tumor - Clear cell myomelanocytic tumor of falciform ligament/ligamentum teres - Abdominopelvic sarcoma of perivascular epithelioid cells - Primary extrapulmonary clear cell sugar tumor - Folpe and Colleagues suggested criteria for malignancy based of following three criteria:[6] Size greater than 8.0 cm Mitotic count of 1/50 high power field (HPF) Necrosis - Size greater than 8.0 cm - Mitotic count of 1/50 high power field (HPF) - Necrosis # Pathophysiology - Perivascular epithlioid cell (PEC) is a cell type constantly present in a group of tumors called PEComas. It has no normal counterpart. - PEC expresses myogenic and melanocytic markers such as HMB45 and actin.[7] ## Microscopic Pathology - Perivascular epithlioid cells (PECs) are perivascular epithelioid cells with a clear/granular cytoplasm and round, oval, centrally located nucleus without prominent nucleoli. They have mild to any atypia.[7] - On ultrastructural analysis, PEC contains microfilament bundles with electron dense condensation, numerous mitochondria and membrane bound dense granules.[8] ## Genetics - The precursor cell of PEComas is currently unknown. Genetically, PECs are linked to the tuberous sclerosis genes TSC1 and TSC2.[7] # Causes - PEComas are cause by genetic factors. Mutations in the tuberous sclerosis genes TSC1 and TSC2 has been associated.[7] # Differentiating PEComa from other Diseases - PEComas must be differentiated from:[6] Epithelioid smooth muscle cell tumors(epithelioid leiomyosarcoma and epithelioid leiomyoma) Malignant Melanoma Clear cell sarcoma of tendon and aponeurosis(melanoma of soft parts) Alveolar soft part sarcoma endometrial stromal sarcoma with clear cell features Carcinoma (especially renal cell and adrenocortical carcinoma) Paraganglioma Any other tumor with focal or prominent clear cell change - Epithelioid smooth muscle cell tumors(epithelioid leiomyosarcoma and epithelioid leiomyoma) - Malignant Melanoma - Clear cell sarcoma of tendon and aponeurosis(melanoma of soft parts) - Alveolar soft part sarcoma - endometrial stromal sarcoma with clear cell features - Carcinoma (especially renal cell and adrenocortical carcinoma) - Paraganglioma - Any other tumor with focal or prominent clear cell change # Epidemiology and Demographics - Patients of all age groups may develop PEComas, but the mean age at diagnosis is 54 years.[9] - Women are more commonly affected by PEComas than men. # Risk Factors - There are no established risk factors for PEComas, but the risk increases in patients with tuberous sclerosis as the PECs are associated with TSC1 and TSC2 genes. # Screening - There is insufficient evidence to recommend routine screening for PEComas. # Natural History, Complications, and Prognosis - Clinically, most PEComas follow a benign course.[10] - Malignant PEComas are also reported, many originating in the uterus and others arising in the prostate, jejunum, pelvis, broad ligament and somatic soft tissue. - They can metastasize distally to liver, lungs, intestines, bone and lymph nodes[11] # Diagnosis ## Diagnostic Study of Choice - There are no established criteria for the diagnosis of PEComas. ## History and Symptoms - The symptoms of PEComa depend on the area involved: Palpable abdominal masses or abnormal vaginal bleeding (uterus)[12] Flank pain (kidneys)[13] Dull abdominal pain in right upper quadrant (liver)[14] - Palpable abdominal masses or abnormal vaginal bleeding (uterus)[12] - Flank pain (kidneys)[13] - Dull abdominal pain in right upper quadrant (liver)[14] ## Physical Examination - There are no any specific physical examination findings related to the PEComas. ## Laboratory findings ### Immunohistochemical markers - PECs typically stain for melanocytic markers (HMB-45, HMSA-1, Melan A (Mart 1), microophthalmia transcription factor (Mitf), myogenic markers (actin), and less commonly desmin. - Immunoreactivity for vimentin is unclear.[7] ## Electrocardiogram - There are no ECG findings associated with PEComas. ## X-ray - There are no x-ray findings associated with PEComas. ## Echocardiography or Ultrasound - There are no echocardiography/ultrasound findings associated with PEComas. ## CT scan - CT scan may be helpful in the diagnosis of PEComas. Findings on CT scan suggestive of PEComas include: - Hypodense (15-50 hours field units) partially solid and partially cystic tumor with moderate contrast uptake (in kidney).[13] Hypervascular tumor with delayed washout pattern in portal venous phase (in liver).[14] Mass with no other pathology (in uterus).[12] - Hypodense (15-50 hours field units) partially solid and partially cystic tumor with moderate contrast uptake (in kidney).[13] - Hypervascular tumor with delayed washout pattern in portal venous phase (in liver).[14] - Mass with no other pathology (in uterus).[12] ## MRI - There are no MRI findings associated with PEComas. ## Other Imaging Findings - There are no other imaging findings associated with PEComas. ## Other Diagnostic Studies - There are no other diagnostic studies associated with PEComas. # Treatment ## Medical Therapy - There is no established medical therapy for PEComas. - Following chemotherapeutic and immunotherapeutic drugs have been tried with mixed results: [15][16][17] Dacarbazine Doxorubicin Vincristine Imatinib mesylate Interferon alpha-b2 - Dacarbazine - Doxorubicin - Vincristine - Imatinib mesylate - Interferon alpha-b2 ## Surgery - Surgery is the mainstay of treatment for PEComas, as well as for local recurrences and metastasis, with the aim of obtaining clear resection margins.[18] ## Primary Prevention - There are no established measures for the primary prevention of PEComas. ## Secondary Prevention - There are no established measures for the secondary prevention of PEComas.	https://www.wikidoc.org/index.php/PEComa
20c45e38697a76519602eac18609db06effc3bab	wikidoc	PELP-1	PELP-1 Proline-, glutamic acid- and leucine-rich protein 1 (PELP1) also known as modulator of non-genomic activity of estrogen receptor (MNAR) and transcription factor HMX3 is a protein that in humans is encoded by the PELP1 gene. is a transcriptional corepressor for nuclear receptors such as glucocorticoid receptors and a coactivator for estrogen receptors. Proline-, glutamic acid-, and leucine-rich protein 1 (PELP1) is transcription coregulator and modulates functions of several hormonal receptors and transcription factors. PELP1 plays essential roles in hormonal signaling, cell cycle progression, and ribosomal biogenesis. PELP1 expression is upregulated in several cancers; its deregulation contributes to hormonal therapy resistance and metastasis; therefore, PELP1 represents a novel therapeutic target for many cancers. # Gene PELP1 is located on chromosome 17p13.2 and PELP1 is expressed in a wide variety of tissues; its highest expression levels are found in the brain, testes, ovaries, and uterus. Currently, there are two known isoforms (long 3.8 Kb and short 3.4 Kb) and short isoform is widely expressed in cancer cells. # Structure The PELP1 protein encodes a protein of 1130 amino acids, and exhibits both cytoplasmic and nuclear localization depending on the tissue. PELP1 lacks known enzymatic activity and functions as a scaffolding protein. It contains 10 NR-interacting boxes (LXXLL motifs) and functions as a coregulator of several nuclear receptors via its LXXLL motifs including ESR1, ESR2, ERR-alpha, PR, GR, AR, and RXR. PELP1 also functions as a coregulator of several other transcription factors, including AP1, SP1, NFkB, STAT3, and FHL2. PELP1 has a histone binding domain and interacts with chromatin-modifying complexes, including CBP/p300, histone deacetylase 2, histones, SUMO2, lysine-specific demethylase 1 (KDM1), PRMT6, and CARM1. PELP1 also interacts with cell cycle regulators such as pRb. E2F1, and p53. PELP1 is phosphorylated by hormonal and growth factor signals. PELP1 phosphorylation status is also influenced by cell cycle progression, and it is a substrate of CDKs. Further, PELP1 is phosphorylated by DNA damage induced kinases (ATM, ATR, DNA-PKcs). # Function PELP1 functions as a coactivator of several NRs and regulates genes involved in proliferation and cancer progression. PELP1 enhances transcription functions of ESR1, ESR2, AR, GR, E2F and STAT3. PELP1 participates in activation of ESR1 extra-nuclear actions by coupling ESR1 with Src kinase PI3K STAT3 ILK1 and mTOR PELP1 participates in E2-mediated cell proliferation and is a substrate of CDK4/cyclin D1, CDK2/cyclin E and CDK2/cyclin A complexes. Studies using TG mice model suggested the existence of an autocrine loop involving the CDK–cyclin D1–PELP1 axis in promoting mammary tumorigenesis PELP1 has a histone binding domain; functions as a reader of histone modifications, interacts with epigenetic modifiers such as HDAC2, KDM1, PRMT6, CARM1; and facilitates activation of genes involved in proliferation and cancer progression. PELP1 modulates the expression of miRs, PELP1-mediated epigenetic changes play important role in the regulation miR expression and many of PELP1 mediated miRS are involved in promoting metastasis. PELP1 is needed for optimal DNA damage response, is phosphorylated by DDR kinases and is important for p53 coactivation function. PELP1 also interacts with MTp53, regulates its recruitment, and alters MTp53 target gene expression. PELP1 depletion contributes to increased stability of E2F1. PELP1 binds RNA, and participates in RNA splicing. The PELP1-regulated genome includes several uniquely spliced isoforms. Mechanistic studies showed that PELP1 interaction with the arginine methyltransferase PRMT6 plays a role in RNA splicing. PELP1 plays critical roles in 60S ribosomal subunit synthesis and ribosomal RNA transcription. The SENP3-associated complex comprising PELP1, TEX10 and WDR18 is involved in maturation and nucleolar release of the large ribosomal subunit. SUMO conjugation/deconjugation of PELP1 controls its dynamic association with the AAA ATPase MDN1, a key factor of pre-60S remodeling. Modification of PELP1 promotes the recruitment of MDN1 to pre-60S particles, while deSUMOylation is needed to release both MDN1 and PELP1 from pre-ribosomes. PELP1 is widely expressed in many regions of brain, including the hippocampus, hypothalamus, and cerebral cortex. PELP1 interacts with ESR1, Src, PI3K and GSK3β in the brain. It is essential for E2-mediated extra-nuclear signaling following global cerebral ischemic. PELP1 plays an essential role in E2-mediated rapid extranuclear signaling, neuroprotection, and cognitive function in the brain. Ability of E2 to exert anti-inflammatory effects was lost in PELP1 forebrain-specific knockout mice, indicating a key role for PELP1 in E2 anti-inflammatory signaling. PELP1 is a proto-oncogene that provides cancer cells with a distinct growth and survival advantage. PELP1 interacts with various enzymes that modulate the cytoskeleton, cell migration, and metastasis. PELP1 deregulation in vivo promotes development of mammary gland hyperplasia and carcinoma PELP1 is implicated in progression of breast, endometrial, ovarian, salivary prostate, lung, pancreas, and colon neoplasms. PELP1 signaling contributes to hormonal therapy resistance. Altered localization of PLP1 contributes to tamoxifen resistance via excessive activation of the AKT pathway and cytoplasmic PELP1 induces signaling pathways that converge on ERRγ to promote cell survival in the presence of tamoxifen. AR, PELP1 and Src form constitutive complexes in prostate neoplasms model cells that exhibit androgen independence. Cytoplasmic localization of PELP1 upregulates pro-tumorigenic IKKε and secrete inflammatory signals, which through paracrine macrophage activation, regulate the migratory phenotype associated with breast cancer initiation. # Clinical significance PELP1 is a proto-oncogene that provides cancer cells with a distinct growth and survival advantage. PELP1 overexpression has been reported in many cancers. PELP1 expression is an independent prognostic predictor of shorter breast cancer–specific survival and disease free interval. Patients whose tumors had high levels of cytoplasmic PELP1 exhibited a tendency to respond poorly to tamoxifen and PELP1 deregulated tumors respond to Src kinase and mTOR inhibitors. Treatment of breast and ovarian cancer xenografts with liposomal PELP1–siRNA–DOPC formulations revealed that knockdown of PELP1 significantly reduce the tumor growth. These results provided initial proof that PELP1 is a bonafide therapeutic target. Emerging data support a central role for PELP1 and its direct protein–protein interactions in cancer progression. Since PELP1 lacks known enzymatic activity, drugs that target PELP1 interactions with other proteins should have clinical utility. Recent studies described an inhibitor (D2) that block PELP1 interactions with AR. Since PELP1 interacts with histone modifications and epigenetic enzymes, drugs targeting epigenetic modifier enzymes may be useful in targeting PELP1 deregulated tumors. # Notes	PELP-1 Proline-, glutamic acid- and leucine-rich protein 1 (PELP1) also known as modulator of non-genomic activity of estrogen receptor (MNAR) and transcription factor HMX3 is a protein that in humans is encoded by the PELP1 gene.[1] is a transcriptional corepressor for nuclear receptors such as glucocorticoid receptors[2] and a coactivator for estrogen receptors.[3] Proline-, glutamic acid-, and leucine-rich protein 1 (PELP1) is transcription coregulator and modulates functions of several hormonal receptors and transcription factors.[4][5] PELP1 plays essential roles in hormonal signaling, cell cycle progression, and ribosomal biogenesis.[6][7] PELP1 expression is upregulated in several cancers; its deregulation contributes to hormonal therapy resistance and metastasis; therefore, PELP1 represents a novel therapeutic target for many cancers.[8][9] # Gene PELP1 is located on chromosome 17p13.2 and PELP1 is expressed in a wide variety of tissues; its highest expression levels are found in the brain, testes, ovaries, and uterus.[3][10][11][12] Currently, there are two known isoforms (long 3.8 Kb and short 3.4 Kb) and short isoform is widely expressed in cancer cells.[13] # Structure The PELP1 protein encodes a protein of 1130 amino acids, and exhibits both cytoplasmic and nuclear localization depending on the tissue.[3][3] PELP1 lacks known enzymatic activity and functions as a scaffolding protein. It contains 10 NR-interacting boxes (LXXLL motifs)[3] and functions as a coregulator of several nuclear receptors via its LXXLL motifs including ESR1,[3] ESR2,[14] ERR-alpha,[15] PR,[16] GR,[2][17] AR,[18][19] and RXR.[20] PELP1 also functions as a coregulator of several other transcription factors, including AP1, SP1, NFkB,[2] STAT3,[21] and FHL2.[19] PELP1 has a histone binding domain and interacts with chromatin-modifying complexes, including CBP/p300,[3] histone deacetylase 2,[2] histones,[2][22] SUMO2,[23] lysine-specific demethylase 1 (KDM1),[24] PRMT6,[25] and CARM1.[26] PELP1 also interacts with cell cycle regulators such as pRb.[13] E2F1,[27] and p53.[28] PELP1 is phosphorylated by hormonal and growth factor signals.[29][30] PELP1 phosphorylation status is also influenced by cell cycle progression, and it is a substrate of CDKs.[31] Further, PELP1 is phosphorylated by DNA damage induced kinases (ATM, ATR, DNA-PKcs).[28] # Function PELP1 functions as a coactivator of several NRs and regulates genes involved in proliferation and cancer progression. PELP1 enhances transcription functions of ESR1, ESR2, AR, GR, E2F and STAT3.[4][4][4][5][5][7] PELP1 participates in activation of ESR1 extra-nuclear actions[4][29] by coupling ESR1 with Src kinase[32] PI3K[33] STAT3 [21] ILK1 [32] and mTOR[34] PELP1 participates in E2-mediated cell proliferation and is a substrate of CDK4/cyclin D1, CDK2/cyclin E and CDK2/cyclin A complexes.[31] Studies using TG mice model suggested the existence of an autocrine loop involving the CDK–cyclin D1–PELP1 axis in promoting mammary tumorigenesis [35] PELP1 has a histone binding domain; functions as a reader of histone modifications, interacts with epigenetic modifiers such as HDAC2, KDM1, PRMT6, CARM1; and facilitates activation of genes involved in proliferation and cancer progression.[2][2][22][24][25][26] PELP1 modulates the expression of miRs, PELP1-mediated epigenetic changes play important role in the regulation miR expression and many of PELP1 mediated miRS are involved in promoting metastasis.[36] PELP1 is needed for optimal DNA damage response, is phosphorylated by DDR kinases and is important for p53 coactivation function.[28] PELP1 also interacts with MTp53, regulates its recruitment, and alters MTp53 target gene expression. PELP1 depletion contributes to increased stability of E2F1.[27] PELP1 binds RNA, and participates in RNA splicing. The PELP1-regulated genome includes several uniquely spliced isoforms. Mechanistic studies showed that PELP1 interaction with the arginine methyltransferase PRMT6 plays a role in RNA splicing.[25] PELP1 plays critical roles in 60S ribosomal subunit synthesis and ribosomal RNA transcription. The SENP3-associated complex comprising PELP1, TEX10 and WDR18 is involved in maturation and nucleolar release of the large ribosomal subunit.[37][38][39] SUMO conjugation/deconjugation of PELP1 controls its dynamic association with the AAA ATPase MDN1, a key factor of pre-60S remodeling. Modification of PELP1 promotes the recruitment of MDN1 to pre-60S particles, while deSUMOylation is needed to release both MDN1 and PELP1 from pre-ribosomes.[40] PELP1 is widely expressed in many regions of brain, including the hippocampus, hypothalamus, and cerebral cortex. PELP1 interacts with ESR1, Src, PI3K and GSK3β in the brain. It is essential for E2-mediated extra-nuclear signaling following global cerebral ischemic.[6][10] PELP1 plays an essential role in E2-mediated rapid extranuclear signaling, neuroprotection, and cognitive function in the brain.[41] Ability of E2 to exert anti-inflammatory effects was lost in PELP1 forebrain-specific knockout mice, indicating a key role for PELP1 in E2 anti-inflammatory signaling.[42] PELP1 is a proto-oncogene[43] that provides cancer cells with a distinct growth and survival advantage.[5][9] PELP1 interacts with various enzymes that modulate the cytoskeleton, cell migration, and metastasis.[43][44][45][45] PELP1 deregulation in vivo promotes development of mammary gland hyperplasia and carcinoma [35] PELP1 is implicated in progression of breast,[27][34][43][46] endometrial,[14] ovarian,[33] salivary[47] prostate,[18][19] lung,[48] pancreas,[49] and colon[50] neoplasms. PELP1 signaling contributes to hormonal therapy resistance.[4][9][9][51] Altered localization of PLP1 contributes to tamoxifen resistance via excessive activation of the AKT pathway [29][52] and cytoplasmic PELP1 induces signaling pathways that converge on ERRγ to promote cell survival in the presence of tamoxifen.[53] AR, PELP1 and Src form constitutive complexes in prostate neoplasms model cells that exhibit androgen independence.[54] Cytoplasmic localization of PELP1 upregulates pro-tumorigenic IKKε and secrete inflammatory signals, which through paracrine macrophage activation, regulate the migratory phenotype associated with breast cancer initiation.[55] # Clinical significance PELP1 is a proto-oncogene that provides cancer cells with a distinct growth and survival advantage. PELP1 overexpression has been reported in many cancers. PELP1 expression is an independent prognostic predictor of shorter breast cancer–specific survival and disease free interval.[56] Patients whose tumors had high levels of cytoplasmic PELP1 exhibited a tendency to respond poorly to tamoxifen [52] and PELP1 deregulated tumors respond to Src kinase[51] and mTOR inhibitors.[34] Treatment of breast and ovarian cancer xenografts with liposomal PELP1–siRNA–DOPC formulations revealed that knockdown of PELP1 significantly reduce the tumor growth.[33][57] These results provided initial proof that PELP1 is a bonafide therapeutic target. Emerging data support a central role for PELP1 and its direct protein–protein interactions in cancer progression. Since PELP1 lacks known enzymatic activity, drugs that target PELP1 interactions with other proteins should have clinical utility. Recent studies described an inhibitor (D2) that block PELP1 interactions with AR.[58] Since PELP1 interacts with histone modifications and epigenetic enzymes, drugs targeting epigenetic modifier enzymes may be useful in targeting PELP1 deregulated tumors.[24][25][26][57] # Notes	https://www.wikidoc.org/index.php/PELP-1
a1f467c8d8b18385707a4f9074ed8996fa1c58ff	wikidoc	PET100	PET100 PET100 homolog is a protein that in humans is encoded by the PET100 gene. Mitochondrial complex IV, or cytochrome c oxidase, is a large transmembrane protein complex that is part of the respiratory electron transport chain of mitochondria. The small protein encoded by the PET100 gene plays a role in the biogenesis of mitochondrial complex IV. This protein localizes to the inner mitochondrial membrane and is exposed to the intermembrane space. Mutations in this gene are associated with mitochondrial complex IV deficiency. This gene has a pseudogene on chromosome 3. Alternative splicing results in multiple transcript variants. # Structure The PET100 gene is located on the p arm of chromosome 19 in position 13.2 and spans 1,839 base pairs. The gene produces a 9.1 kDa protein composed of 73 amino acids. The encoded protein localizes to the inner mitochondrial membrane and is exposed to the intermembrane space. This protein's N-terminus is essential for mitochondrial localization. It assembles into a 300 kDA complex which is dependent on the mitochondrial membrane potential, accumulating over time. # Function The protein encoded by PET100 is involved in Complex IV biogenesis as a COX chaperone; it is required for interaction between MR-1S, PET117, and Complex IV. # Clinical significance In 8 patients of Lebanese origin living in Australia, a c.3G>C mutation in the PET100 gene caused Complex IV deficiency and Leigh syndrome. Symptoms included delayed psychomotor development, seizures, hypotonia, brain abnormalities, and elevated blood and cerebrospinal fluid lactate levels. In another patient of Pakistani origin, a homozygous c.142C>T mutation resulted in Complex IV deficiency with intrauterine growth retardation, metabolic and lactic acidosis, hypoglycemia, coagulopathy, elevated serum creatine kinase levels, seizures, and intraventricular cysts. # Interactions The encoded protein interacts with MR-1S and COX7A2. This protein is required for MR-1S, PET117, and Complex IV to interact.	PET100 PET100 homolog is a protein that in humans is encoded by the PET100 gene. Mitochondrial complex IV, or cytochrome c oxidase, is a large transmembrane protein complex that is part of the respiratory electron transport chain of mitochondria. The small protein encoded by the PET100 gene plays a role in the biogenesis of mitochondrial complex IV. This protein localizes to the inner mitochondrial membrane and is exposed to the intermembrane space. Mutations in this gene are associated with mitochondrial complex IV deficiency. This gene has a pseudogene on chromosome 3. Alternative splicing results in multiple transcript variants.[1] # Structure The PET100 gene is located on the p arm of chromosome 19 in position 13.2 and spans 1,839 base pairs.[1] The gene produces a 9.1 kDa protein composed of 73 amino acids.[2][3] The encoded protein localizes to the inner mitochondrial membrane and is exposed to the intermembrane space. This protein's N-terminus is essential for mitochondrial localization. It assembles into a 300 kDA complex which is dependent on the mitochondrial membrane potential, accumulating over time.[4][5] # Function The protein encoded by PET100 is involved in Complex IV biogenesis as a COX chaperone; it is required for interaction between MR-1S, PET117, and Complex IV.[1][6] # Clinical significance In 8 patients of Lebanese origin living in Australia, a c.3G>C mutation in the PET100 gene caused Complex IV deficiency and Leigh syndrome. Symptoms included delayed psychomotor development, seizures, hypotonia, brain abnormalities, and elevated blood and cerebrospinal fluid lactate levels.[5] In another patient of Pakistani origin, a homozygous c.142C>T mutation resulted in Complex IV deficiency with intrauterine growth retardation, metabolic and lactic acidosis, hypoglycemia, coagulopathy, elevated serum creatine kinase levels, seizures, and intraventricular cysts.[7][4] # Interactions The encoded protein interacts with MR-1S and COX7A2.[8][9] This protein is required for MR-1S, PET117, and Complex IV to interact.	https://www.wikidoc.org/index.php/PET100
d17a6a121f2b49d7b2035b6d97007d13bff52fd7	wikidoc	PET117	PET117 PET117 homolog is a protein that in humans is encoded by the PET117 gene. Localized to mitochondria, this protein is a chaperone protein involved in the assembly of mitochondrial Complex IV, or Cytochrome C Oxidase. Mutations in this gene can cause Complex IV deficiency with symptoms including medulla oblongata lesions and lactic acidosis. # Structure The PET117 gene is located on the p arm of chromosome 20 in position 11.23 and spans 5,314 base pairs. The gene produces a 9.2 kDa protein composed of 81 amino acids. PET117 localizes to mitochondria. # Function The protein encoded by PET117 is a chaperone protein involved in Complex IV biogenesis, interacting with MR-1S and possibly other Complex IV structural subunits. The presence of PET100 is required for this interaction. # Clinical Significance The only reported mutation in the PET117 gene was a homozygous nonsense mutation (c. 172 C>T) in two sister patients. Both were diagnosed with Complex IV deficiency and had lesions in their medulla oblongata, along with lactic acidosis. Symptoms in the older sister included abnormal motor development, regression in speech and motor skills after age ten, bradykinesia, hypokinesia, and pyramidal signs with positive Babinski response. The younger sister had protein losing enteropathy (PLE), recurrent respiratory infections, neutropenia, hypogammaglobulinemia, delayed motor and general development, and exercise intolerance. # Interactions PET117 interacts with MR-1S and possibly other Complex IV structural subunits. This interaction is dependent on the presence of PET100.	PET117 PET117 homolog is a protein that in humans is encoded by the PET117 gene.[1] Localized to mitochondria, this protein is a chaperone protein involved in the assembly of mitochondrial Complex IV, or Cytochrome C Oxidase.[2][3] Mutations in this gene can cause Complex IV deficiency with symptoms including medulla oblongata lesions and lactic acidosis.[4] # Structure The PET117 gene is located on the p arm of chromosome 20 in position 11.23 and spans 5,314 base pairs.[1] The gene produces a 9.2 kDa protein composed of 81 amino acids.[5][6] PET117 localizes to mitochondria.[3] # Function The protein encoded by PET117 is a chaperone protein involved in Complex IV biogenesis, interacting with MR-1S and possibly other Complex IV structural subunits. The presence of PET100 is required for this interaction.[2] # Clinical Significance The only reported mutation in the PET117 gene was a homozygous nonsense mutation (c. 172 C>T) in two sister patients. Both were diagnosed with Complex IV deficiency and had lesions in their medulla oblongata, along with lactic acidosis. Symptoms in the older sister included abnormal motor development, regression in speech and motor skills after age ten, bradykinesia, hypokinesia, and pyramidal signs with positive Babinski response. The younger sister had protein losing enteropathy (PLE), recurrent respiratory infections, neutropenia, hypogammaglobulinemia, delayed motor and general development, and exercise intolerance.[4] # Interactions PET117 interacts with MR-1S and possibly other Complex IV structural subunits. This interaction is dependent on the presence of PET100.[2]	https://www.wikidoc.org/index.php/PET117
59dd6cd40d46cac84995e2c40248bdcebb70c18b	wikidoc	PFKFB3	PFKFB3 PFKFB3 is a gene that encodes the 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 enzyme in humans. It is one of 4 tissue-specific PFKFB isoenzymes identified currently (PFKFB1-4). # Gene The PFKFB3 gene is mapped to single locus on chromosome 10 (10p15-p14). It spans a region of 32.5kb with an open reading frame that is 5,675bp long. It is estimated to consist of 19 exons, of which 15 are regularly expressed. Alternative splicing of the variable, COOH-terminal domain has been observed, leading to 6 different isoforms termed UBI2K1 to UBI2K6 in humans. Different nomenclature also recognizes two broad categories of PFKFB3 isoforms, termed ‘inducible’ and ‘ubiquitous’. The inducible protein isoform, iPFK2, is named as such because its expression has been shown to be induced by hypoxic conditions. The PFKFB3 promoter is predicted to contain multiple binding sites, including Sp-1 and AP-2 binding sites. It also contains motifs for the binding of E-box, nuclear factor-1 (NF-1), and progesterone response element. Expression of the promoter is shown to be induce by phorbol esters and cyclic-AMP-dependent protein kinase signaling. # Structure The four PFKFB isoforms share high (85%) ‘2-Kase/2-Pase core’ sequence homology, but have different properties based on variable N- and C- terminal regulatory domains and variation in residues surrounding the active sites. The PFKFB3 inducible isoform has higher ‘2-Kase’ (kinase) activity than other isoforms, due to phosphorylation of Ser-460 by PKA or AMP-dependent protein kinase. The high ‘2-Kase’ activity of PFKFB3 is also due to the lack of a specific Ser that is phosphorylated in the other PFKFB isoforms to decrease kinase activity. The primary protein encoded by PFKFB3, iPFK2, consists of 590 amino acids. It has a predicted molecular weight of 66.9 kDa and an isoelectric point of 8.64. The crystal structure was determined in 2006: - Researcher found that iPFK2 has a beta-hairpin N-terminal structure that secures the binding of fructose-6-phosphate to the active site via interaction with the protein’s ‘2-Pase’ domain. There are two active pockets within iPFK2 for fructose-2,6-bisphosphatase and 6-phosphofructo-2-kinase which are structurally different. The F-2,6-BP active site structurally open, while the active pocket of 6-phosphofructo-2-kinase is more rigid. This rigidity permits the independent binding of F-6-P and ATP with increased affinity than other isoforms. # Function iPFK2 converts fructose-6-phosphate to fructose-2,6-bisP (F2,6BP). F2,6BP is a ‘potent’ allosteric activator of 6-phosphofructokinase-1 (PFK-1), stimulating glycolysis. Click to see image of PFFKB3 function. # Cancer Connections ## Warburg Effect The Warburg effect, proposed by Otto Warbug in 1956, describes the upregulation of glycolysis in most cancer cells, even in the presence of oxygen. The high rate of glycolysis is accompanied by increased lactic acid fermentation, providing additional nutrients for cancer cell growth and tumorigenesis. PFKFB3 is associated with the Warburg effect because its activity increases the rate of glycolysis. PFKFB3 has been found to be upregulated in numerous cancers, including colon, breast, ovarian, and thyroid. Reduced methylation of PFKFB3 is also found in some cancers, triggering the shift to the glycolytic pathway that supports cancerous growth. ## Hypoxia Signaling Pathway PFKFB3 expression is induced by hypoxia. The promoter of PFKFB3 contains binding sites, called hypoxia response elements (HREs), that recruit the binding of hypoxia-inducible factor-1 (HIF-1). Hypoxia signaling via HIF-1α stabilization upregulates the transcription of genes that permit survival in low oxygen conditions. These genes include glycolysis enzymes, like PFKFB3, that permit ATP synthesis without oxygen, and vascular endothelial growth factor (VEGF), which promotes angiogenesis. ## Cell Cycle & Apoptosis It was more recently discovered that PFKFB3 promotes cell cycle progression (cell proliferation) and suppresses apoptosis by regulating cyclin-dependent kinase 1 (Cdk-1). PFKFB3’s synthesis of F2,6BP in the nucleus was found to regulate Cdk-1, whereas cytosolic PFKFB3 activates PFK-1. Nuclear PFKFB3 activates Cdk1 to phosphorylate the Thr-187 site of p27, causing decreased levels of p27. (See summary figure). Reduced p27 causes protection against apoptosis and progression of cells through the G1/S phase checkpoint These findings established a significant link between PFKFB3 cancer cell survival and proliferation. ## Circadian Clock Circadian clocks dysregulation is associated with many types of cancer. PFKFB3 expression exhibits circadian rhythmicity that is different between cancerous and non-cancerous cells. It was specifically found that the circadian-driven transcription factor ‘CLOCK’ binds to the PFKFB3 promoter at a genuine ‘E-box’ site to increase transcription in cancer cells. - Inhibition of PFKFB3 using 3PO was successful in reducing cancer growth and increasing apoptosis, but only at certain time points within the circadian cycle. This finding highlights the need for time-based PFKFB3 inhibition in cancer treatment. The role of PFKFB3 inhibition in this process should now be considered taking recent information into account that 3PO was shown not to be a PFKFB3 inhibitor (3PO was inactive in a kinase PFKFB3 inhibition assay (IC50 > 100 µM)) ## Additional Cancer Connections - PFKFB3 is activated by progestins in breast cancer cells - PFKFB3 promotes angiogenesis Silencing of PFKFB3 impairs angiogenesis. PFKFB3-driven glycolysis overrules the pro-stalk activity of Notch. PFKFB3 regulates tip and stalk cell behavior and compartmentalizes with F-actin. - Silencing of PFKFB3 impairs angiogenesis. PFKFB3-driven glycolysis overrules the pro-stalk activity of Notch. PFKFB3 regulates tip and stalk cell behavior and compartmentalizes with F-actin. ## Anti-cancer Therapeutic Strategy Inhibition of PFKFB3 is being analyzed as a potential anti-cancer therapy. Several small molecule inhibitors of PFKFB3 are currently in development. For a long time a small molecule 3-(3-pyridinyl)-1-(4-pyridinyl)-2-propen-1-one (3PO) was believed to be an inhibitor of PFKFB3 and used as PFKFB3 inhibitor in many scientific publications and even went into clinical trial as PFKFB3 inhibitor. Recent research of one of the leading pharmaceuticals companies AstraZeneca and CRT Discovery Laboratories of world's largest independent cancer research charity Cancer Research UK showed that 3PO was inactive in a kinase PFKFB3 inhibition assay (IC50 > 100 µM). The findings of AstraZeneca and Cancer Research UK regarding to 3PO remain unchallenged neither by 3PO developers nor by scientific community since April 7, 2015. The crystal structures of 3PO, as well as its analogues PFK15 and PFK158, with the PFKFB3 enzyme are also not available. These AstraZeneca and Cancer Research UK findings put into question the range of the scientific research and publications where 3PO was used as a PFKFB3 inhibitor. 3PO decreases glucose uptake and increases autophagy. Research is currently exploring various 3PO derivatives (i.e. PFKF15) in an effort to increase their efficacy as anti-cancer therapies, but the data on 3PO derivatives being actually PFKFB3 inhibitors are also unavailable. # Other Pathways Involving PFKFB3 ## Autophagy Enhanced activity of PFKFB3 accelerates ROS production as an end product of glycolysis, and thus increases autophagy. Likewise, inhibition of PFKFB3 has been found to induce autophagy. See summary image. Autophagy can prolong cellular survival during low energy conditions. This finding was discovered in relation to rheumatoid arthritis. It was found that RA T cell fail to upregulate autophagy, and knockout experiments placed PFKFB3 as an upstream regulator of this process. ## Insulin Signaling Pathway PFKFB3 was identified in a kinome screen as a regulator of insulin/IGF-1. Suppression of PFKFB3 was found to decrease insulin-stimulated glucose uptake, GLUT4 translocation, and Akt signaling in 3T3-L1 adipocytes. Overexpression caused the insulin-dependent phosphorylation of Akt and Akt substrates. PFKFB3 expression increases in fat tissues during adipogenesis, but prolonged insulin exposure has been shown to decrease the expression of PFKFB3. This is thought to occur due to a negative feedback mechanism involving insulin. ## p38/MK2 Stress Sigaling Pathway p38 MAPK have been found to increase PFKFB3 activity through (1) the transcriptional activation of PFKFB3 in response to stress stimuli and (2) the post-translational phosphorylation of iPFK2 at Ser-461. See summary figure.	PFKFB3 PFKFB3 is a gene that encodes the 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 enzyme in humans.[1][2][3] It is one of 4 tissue-specific PFKFB isoenzymes identified currently (PFKFB1-4).[4] # Gene The PFKFB3 gene is mapped to single locus on chromosome 10 (10p15-p14).[1][2] It spans a region of 32.5kb with an open reading frame that is 5,675bp long. It is estimated to consist of 19 exons, of which 15 are regularly expressed.[4] Alternative splicing of the variable, COOH-terminal domain has been observed, leading to 6 different isoforms termed UBI2K1 to UBI2K6 in humans.[5] Different nomenclature also recognizes two broad categories of PFKFB3 isoforms, termed ‘inducible’ and ‘ubiquitous’.[6] The inducible protein isoform, iPFK2, is named as such because its expression has been shown to be induced by hypoxic conditions. The PFKFB3 promoter is predicted to contain multiple binding sites, including Sp-1 and AP-2 binding sites. It also contains motifs for the binding of E-box, nuclear factor-1 (NF-1), and progesterone response element. Expression of the promoter is shown to be induce by phorbol esters and cyclic-AMP-dependent protein kinase signaling.[6] # Structure The four PFKFB isoforms share high (85%) ‘2-Kase/2-Pase core’ sequence homology, but have different properties based on variable N- and C- terminal regulatory domains and variation in residues surrounding the active sites.[7] The PFKFB3 inducible isoform has higher ‘2-Kase’ (kinase) activity than other isoforms, due to phosphorylation of Ser-460 by PKA or AMP-dependent protein kinase.[7] The high ‘2-Kase’ activity of PFKFB3 is also due to the lack of a specific Ser that is phosphorylated in the other PFKFB isoforms to decrease kinase activity.[8] The primary protein encoded by PFKFB3, iPFK2, consists of 590 amino acids. It has a predicted molecular weight of 66.9 kDa and an isoelectric point of 8.64.[4] The crystal structure was determined in 2006:[7] - Researcher found that iPFK2 has a beta-hairpin N-terminal structure that secures the binding of fructose-6-phosphate to the active site via interaction with the protein’s ‘2-Pase’ domain. There are two active pockets within iPFK2 for fructose-2,6-bisphosphatase and 6-phosphofructo-2-kinase which are structurally different. The F-2,6-BP active site structurally open, while the active pocket of 6-phosphofructo-2-kinase is more rigid. This rigidity permits the independent binding of F-6-P and ATP with increased affinity than other isoforms. # Function iPFK2 converts fructose-6-phosphate to fructose-2,6-bisP (F2,6BP). F2,6BP is a ‘potent’ allosteric activator of 6-phosphofructokinase-1 (PFK-1), stimulating glycolysis. Click to see image of PFFKB3 function[permanent dead link]. # Cancer Connections ## Warburg Effect The Warburg effect, proposed by Otto Warbug in 1956,[9] describes the upregulation of glycolysis in most cancer cells, even in the presence of oxygen. The high rate of glycolysis is accompanied by increased lactic acid fermentation, providing additional nutrients for cancer cell growth and tumorigenesis. PFKFB3 is associated with the Warburg effect because its activity increases the rate of glycolysis. PFKFB3 has been found to be upregulated in numerous cancers, including colon, breast, ovarian, and thyroid.[10] Reduced methylation of PFKFB3 is also found in some cancers, triggering the shift to the glycolytic pathway that supports cancerous growth.[11] ## Hypoxia Signaling Pathway PFKFB3 expression is induced by hypoxia.[12] The promoter of PFKFB3 contains binding sites, called hypoxia response elements (HREs), that recruit the binding of hypoxia-inducible factor-1 (HIF-1).[13] Hypoxia signaling via HIF-1α stabilization upregulates the transcription of genes that permit survival in low oxygen conditions. These genes include glycolysis enzymes, like PFKFB3, that permit ATP synthesis without oxygen, and vascular endothelial growth factor (VEGF), which promotes angiogenesis. ## Cell Cycle & Apoptosis It was more recently discovered that PFKFB3 promotes cell cycle progression (cell proliferation) and suppresses apoptosis by regulating cyclin-dependent kinase 1 (Cdk-1). PFKFB3’s synthesis of F2,6BP in the nucleus was found to regulate Cdk-1, whereas cytosolic PFKFB3 activates PFK-1. Nuclear PFKFB3 activates Cdk1 to phosphorylate the Thr-187 site of p27, causing decreased levels of p27.[14][15] (See summary figure). Reduced p27 causes protection against apoptosis and progression of cells through the G1/S phase checkpoint These findings established a significant link between PFKFB3 cancer cell survival and proliferation. ## Circadian Clock Circadian clocks dysregulation is associated with many types of cancer.[16] PFKFB3 expression exhibits circadian rhythmicity that is different between cancerous and non-cancerous cells.[17] It was specifically found that the circadian-driven transcription factor ‘CLOCK’ binds to the PFKFB3 promoter at a genuine ‘E-box’ site to increase transcription in cancer cells. - Inhibition of PFKFB3 using 3PO was successful in reducing cancer growth and increasing apoptosis, but only at certain time points within the circadian cycle. This finding highlights the need for time-based PFKFB3 inhibition in cancer treatment. The role of PFKFB3 inhibition in this process should now be considered taking recent information into account that 3PO was shown not to be a PFKFB3 inhibitor (3PO was inactive in a kinase PFKFB3 inhibition assay (IC50 > 100 µM)) [18] ## Additional Cancer Connections - PFKFB3 is activated by progestins in breast cancer cells[19] - PFKFB3 promotes angiogenesis Silencing of PFKFB3 impairs angiogenesis. PFKFB3-driven glycolysis overrules the pro-stalk activity of Notch. PFKFB3 regulates tip and stalk cell behavior and compartmentalizes with F-actin.[20] - Silencing of PFKFB3 impairs angiogenesis. PFKFB3-driven glycolysis overrules the pro-stalk activity of Notch. PFKFB3 regulates tip and stalk cell behavior and compartmentalizes with F-actin.[20] ## Anti-cancer Therapeutic Strategy Inhibition of PFKFB3 is being analyzed as a potential anti-cancer therapy. Several small molecule inhibitors of PFKFB3 are currently in development. For a long time a small molecule 3-(3-pyridinyl)-1-(4-pyridinyl)-2-propen-1-one (3PO) was believed to be an inhibitor of PFKFB3 and used as PFKFB3 inhibitor in many scientific publications and even went into clinical trial as PFKFB3 inhibitor. Recent research of one of the leading pharmaceuticals companies AstraZeneca and CRT Discovery Laboratories of world's largest independent cancer research charity Cancer Research UK showed that 3PO was inactive in a kinase PFKFB3 inhibition assay (IC50 > 100 µM).[18] The findings of AstraZeneca and Cancer Research UK regarding to 3PO remain unchallenged neither by 3PO developers nor by scientific community since April 7, 2015. The crystal structures of 3PO, as well as its analogues PFK15 and PFK158, with the PFKFB3 enzyme are also not available. These AstraZeneca and Cancer Research UK findings put into question the range of the scientific research and publications where 3PO was used as a PFKFB3 inhibitor. 3PO decreases glucose uptake and increases autophagy.[21] Research is currently exploring various 3PO derivatives (i.e. PFKF15)[22] in an effort to increase their efficacy as anti-cancer therapies, but the data on 3PO derivatives being actually PFKFB3 inhibitors are also unavailable. # Other Pathways Involving PFKFB3 ## Autophagy Enhanced activity of PFKFB3 accelerates ROS production as an end product of glycolysis, and thus increases autophagy. Likewise, inhibition of PFKFB3 has been found to induce autophagy.[23][24] See summary image. Autophagy can prolong cellular survival during low energy conditions. This finding was discovered in relation to rheumatoid arthritis.[25] It was found that RA T cell fail to upregulate autophagy, and knockout experiments placed PFKFB3 as an upstream regulator of this process. ## Insulin Signaling Pathway PFKFB3 was identified in a kinome screen as a regulator of insulin/IGF-1. Suppression of PFKFB3 was found to decrease insulin-stimulated glucose uptake, GLUT4 translocation, and Akt signaling in 3T3-L1 adipocytes. Overexpression caused the insulin-dependent phosphorylation of Akt and Akt substrates.[26] PFKFB3 expression increases in fat tissues during adipogenesis, but prolonged insulin exposure has been shown to decrease the expression of PFKFB3. This is thought to occur due to a negative feedback mechanism involving insulin.[27] ## p38/MK2 Stress Sigaling Pathway p38 MAPK have been found to increase PFKFB3 activity through (1) the transcriptional activation of PFKFB3 in response to stress stimuli and (2) the post-translational phosphorylation of iPFK2 at Ser-461.[28][29] See summary figure.[29]	https://www.wikidoc.org/index.php/PFKFB3
4557e8b95eab25d78c8cf921815ad83745e1abca	wikidoc	PFKFB4	PFKFB4 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 4 also known as PFKFB4 is an enzyme which in humans is encoded by the PFKFB4 gene. # Function The bifunctional 6-phosphofructo-2-kinase (EC 2.7.1.105)/fructose-2,6-bisphosphatase (EC 3.1.3.46) (PFKFB) regulates the steady-state concentration of fructose 2,6-bisphosphate, an activator of a key regulatory enzyme of glycolysis, phosphofructokinase. In 2012 research by scientists at Cancer Research UK’s London Research Institute show that an enzyme called PFKFB4 is essential for balancing these two processes – making sure the cell’s energy needs are met without allowing free radicals to build up and trigger cell death. Study leader Dr. Almut Schulze, said: “Our study suggests that PFKFB4 acts to fine-tune the process by which cells convert glucose into energy. Blocking this enzyme in prostate cancer cells grown in the lab stalled growth and triggered a catastrophic build-up of free-radicals, suggesting that it could be a suitable drug target. Importantly, this route to energy production is common to many different types of cancer, suggesting that drugs to target it could potentially be used to treat a variety of cancers.”	PFKFB4 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 4 also known as PFKFB4 is an enzyme which in humans is encoded by the PFKFB4 gene.[1][2] # Function The bifunctional 6-phosphofructo-2-kinase (EC 2.7.1.105)/fructose-2,6-bisphosphatase (EC 3.1.3.46) (PFKFB) regulates the steady-state concentration of fructose 2,6-bisphosphate, an activator of a key regulatory enzyme of glycolysis, phosphofructokinase. In 2012 research by scientists at Cancer Research UK’s London Research Institute show that an enzyme called PFKFB4 is essential for balancing these two processes – making sure the cell’s energy needs are met without allowing free radicals to build up and trigger cell death. Study leader Dr. Almut Schulze, said: “Our study suggests that PFKFB4 acts to fine-tune the process by which cells convert glucose into energy. Blocking this enzyme in prostate cancer cells grown in the lab stalled growth and triggered a catastrophic build-up of free-radicals, suggesting that it could be a suitable drug target. Importantly, this route to energy production is common to many different types of cancer, suggesting that drugs to target it could potentially be used to treat a variety of cancers.”[3]	https://www.wikidoc.org/index.php/PFKFB4
83e71d80fa52a63b84437c6c45d1784b59faff6e	wikidoc	PGRMC1	PGRMC1 Progesterone receptor membrane component 1 (abbreviated PGRMC1) is a protein which co-purifies with progesterone binding proteins in the liver and ovary. In humans, the PGRMC1 protein is encoded by the PGRMC1 gene. The Sigma-2 receptor was recently identified as a protein that binds the PGRMC1 protein. The sole biochemical function of PGRMC1 is heme-binding. PGRMC1 shares key structural motifs with cytochrome b5. PGRMC1 binds and activates P450 proteins, which are important in drug, hormone and lipid metabolism. PGRMC1 also binds to PAIR-BP1 (plasminogen activator inhibitor RNA-binding protein-1). However, its expression outside of the reproductive tract and in males suggests multiple functions for the protein. These may include binding to Insig (insulin-induced gene), which regulates cholesterol synthesis. # Expression PGRMC1 is highly expressed in the liver and kidney in humans with lower expression in the brain, lung, heart, skeletal muscle and pancreas. In rodents, PGRMC1 is found in the liver, lung, kidney and brain. PGRMC1 is over-expressed in breast tumors and in cancer cell lines from the colon, thyroid, ovary, lung, and cervix. Microarray analyses have detected PGRMC1 expression in colon, lung and breast tumors. PGRMC1 expression is induced by the non-genotoxic carcinogen 2,3,7,8-tetrachlorodibenzo-p-dioxin in the rat liver, but this induction is specific to males. PGRMC1 is expressed in the ovary and corpus luteum, where its expression is induced by progesterone and during pregnancy, respectively. PGRMC1/25-Dx is expressed in various regions of the brain including regions known to facilitate lordosis. # Binding to heme and cytochrome P450s The PGRMC1 yeast homologue, Dap1 (damage associated protein 1), binds heme through a penta-coordinate mechanism. Yeast cells lacking the DAP1 gene are sensitive to DNA damage, and heme-binding is essential for damage resistance. Dap1 is also required for a critical step in cholesterol synthesis in which the P450 protein Erg11/Cyp51 removes a methyl group from lanosterol. Erg11/Cyp51 is the target of the azole antifungal drugs. As a result, yeast cells lacking the DAP1 gene are highly sensitive to antifungal drugs This function is conserved between the unrelated fungi S. cerevisiae and S. pombe. Dap1 also regulates the metabolism of iron in yeast. In yeast and humans, PGRMC1 binds directly to P450 proteins, including CYP51A1, CYP3A4, CYP7A1 and CYP21A2. PGRMC1 also activates Cyp21 when the two proteins are co-expressed, indicating that PGRMC1 promotes progesterone turnover. Just as Dap1 is required for the action of Erg11 in the synthesis of ergosterol in yeast, PGRMC1 regulates the Cyp51-catalyzed demethylation step in human cholesterol synthesis. Thus, PGRMC1 and its homologues bind and regulate P450 proteins, and it has been likened to “a helping hand for P450 proteins”. # Roles in signaling and apoptosis The yeast PGRMC1 homologue is required for resistance to damage. PGRMC1 also promotes survival in human cancer cells after treatment with chemotherapy. In contrast, PGRMC1 promotes cell death in cancer cells after oxidative damage. PGRMC1 alters several known survival signaling proteins, including the Akt protein kinase and the cell death-associated protein IκB. Progesterone inhibits apoptosis in immortalized granulosa cells, and this activity requires PGRMC1 and its binding partner, PAIR-BP1 (plasminogen activator inhibitor RNA-binding protein-1). However, PAIR-BP1 is not a progesterone binding protein, and the component of the PGRMC1 complex that binds to progesterone is unknown.	PGRMC1 Progesterone receptor membrane component 1 (abbreviated PGRMC1) is a protein which co-purifies with progesterone binding proteins in the liver and ovary.[1][2] In humans, the PGRMC1 protein is encoded by the PGRMC1 gene.[3] The Sigma-2 receptor was recently identified as a protein that binds the PGRMC1 protein.[4] The sole biochemical function of PGRMC1 is heme-binding.[5][6] PGRMC1 shares key structural motifs with cytochrome b5.[7] PGRMC1 binds and activates P450 proteins,[8][9][10] which are important in drug, hormone and lipid metabolism. PGRMC1 also binds to PAIR-BP1 (plasminogen activator inhibitor RNA-binding protein-1).[2] However, its expression outside of the reproductive tract and in males suggests multiple functions for the protein. These may include binding to Insig (insulin-induced gene),[11] which regulates cholesterol synthesis.[12] # Expression PGRMC1 is highly expressed in the liver and kidney in humans[3] with lower expression in the brain, lung, heart, skeletal muscle and pancreas.[3][13][14] In rodents, PGRMC1 is found in the liver, lung, kidney and brain.[13][14] PGRMC1 is over-expressed in breast tumors and in cancer cell lines from the colon, thyroid, ovary, lung, and cervix.[15][16] Microarray analyses have detected PGRMC1 expression in colon, lung and breast tumors.[17][18][19] PGRMC1 expression is induced by the non-genotoxic carcinogen 2,3,7,8-tetrachlorodibenzo-p-dioxin in the rat liver,[14] but this induction is specific to males.[20] PGRMC1 is expressed in the ovary and corpus luteum, where its expression is induced by progesterone[21] and during pregnancy,[22] respectively. PGRMC1/25-Dx is expressed in various regions of the brain [hypothalamic area, circumventricular organs, ependymal cells of the lateral ventricles, meninges,[13][23] including regions known to facilitate lordosis.[13] # Binding to heme and cytochrome P450s The PGRMC1 yeast homologue, Dap1 (damage associated protein 1), binds heme[6][24] through a penta-coordinate mechanism.[6][25] Yeast cells lacking the DAP1 gene are sensitive to DNA damage,[26] and heme-binding is essential for damage resistance.[24] Dap1 is also required for a critical step in cholesterol synthesis in which the P450 protein Erg11/Cyp51 removes a methyl group from lanosterol.[8][24][26][27] Erg11/Cyp51 is the target of the azole antifungal drugs. As a result, yeast cells lacking the DAP1 gene are highly sensitive to antifungal drugs[8][24][26] This function is conserved between the unrelated fungi S. cerevisiae and S. pombe. Dap1 also regulates the metabolism of iron in yeast.[27] In yeast and humans, PGRMC1 binds directly to P450 proteins, including CYP51A1, CYP3A4, CYP7A1 and CYP21A2.[8] PGRMC1 also activates Cyp21 when the two proteins are co-expressed,[9][10] indicating that PGRMC1 promotes progesterone turnover. Just as Dap1 is required for the action of Erg11 in the synthesis of ergosterol in yeast, PGRMC1 regulates the Cyp51-catalyzed demethylation step in human cholesterol synthesis.[8] Thus, PGRMC1 and its homologues bind and regulate P450 proteins, and it has been likened to “a helping hand for P450 proteins”.[28] # Roles in signaling and apoptosis The yeast PGRMC1 homologue is required for resistance to damage.[26] PGRMC1 also promotes survival in human cancer cells after treatment with chemotherapy.[2][5] In contrast, PGRMC1 promotes cell death in cancer cells after oxidative damage.[29] PGRMC1 alters several known survival signaling proteins, including the Akt protein kinase and the cell death-associated protein IκB.[29] Progesterone inhibits apoptosis in immortalized granulosa cells, and this activity requires PGRMC1 and its binding partner, PAIR-BP1 (plasminogen activator inhibitor RNA-binding protein-1).[2] However, PAIR-BP1 is not a progesterone binding protein, and the component of the PGRMC1 complex that binds to progesterone is unknown.	https://www.wikidoc.org/index.php/PGRMC1
3aba79fe19e4684bd440e081009bdf283c6b1636	wikidoc	PHLDA1	PHLDA1 Pleckstrin homology-like domain family A member 1 (PHLDA1) is a protein that in humans is encoded by the PHLDA1 gene. This gene encodes an evolutionarily conserved proline-histidine rich nuclear protein. The encoded protein may play an important role in the anti-apoptotic effects of insulin-like growth factor-1. # Interactions PHLDA1 has been shown to interact with RPL14, EIF3D and PABPC4.	PHLDA1 Pleckstrin homology-like domain family A member 1 (PHLDA1) is a protein that in humans is encoded by the PHLDA1 gene.[1][2][3] This gene encodes an evolutionarily conserved proline-histidine rich nuclear protein. The encoded protein may play an important role in the anti-apoptotic effects of insulin-like growth factor-1.[3] # Interactions PHLDA1 has been shown to interact with RPL14,[4] EIF3D[4] and PABPC4.[4]	https://www.wikidoc.org/index.php/PHLDA1
864218ebb2a10d24efc0f61109c9675b397f20d3	wikidoc	PHOX2B	PHOX2B Paired-like homeobox 2b (PHOX2B), also known as neuroblastoma Phox (NBPhox), is a protein that in humans is encoded by the PHOX2B gene located on chromosome 4. It codes for a homeodomain transcription factor. It is expressed exclusively in the nervous system, in most neurons that control the viscera (cardiovascular, digestive and respiratory systems). It is also required for their differentiation. # Pathology Mutations in human PHOX2B cause a rare disease of the visceral nervous system (dysautonomia): congenital central hypoventilation syndrome (associated with respiratory arrests during sleep and, occasionally, wakefulness), Hirschsprung's disease (partial agenesis of the enteric nervous system), ROHHAD, and tumours of the sympathetic ganglia. In most people, Exon 3 of the gene contains a sequence of 20 polyalanine repeats. An increase in the number of repeats is associated with congenital central hypoventilation syndrome. There may also be other pathogenic mutations further along the gene.	PHOX2B Paired-like homeobox 2b (PHOX2B), also known as neuroblastoma Phox (NBPhox), is a protein that in humans is encoded by the PHOX2B gene located on chromosome 4.[1] It codes for a homeodomain transcription factor. It is expressed exclusively in the nervous system, in most neurons that control the viscera (cardiovascular, digestive and respiratory systems). It is also required for their differentiation. # Pathology Mutations in human PHOX2B cause a rare disease of the visceral nervous system (dysautonomia): congenital central hypoventilation syndrome (associated with respiratory arrests during sleep and, occasionally, wakefulness), Hirschsprung's disease (partial agenesis of the enteric nervous system), ROHHAD, and tumours of the sympathetic ganglia. In most people, Exon 3 of the gene contains a sequence of 20 polyalanine repeats. An increase in the number of repeats is associated with congenital central hypoventilation syndrome. There may also be other pathogenic mutations further along the gene.	https://www.wikidoc.org/index.php/PHOX2B
cf83c879db6cb09b4c5dc9732301bb95d671316b	wikidoc	PHYLIP	PHYLIP PHYLIP is a free Computational phylogenetics package of programs for inferring evolutionary trees (phylogenies). The name is an acronym for PHYLogeny Inference Package. It consists of 35 portable programs, i.e. The source code is written in C and precompiled executables are available for Windows (95/98/NT/2000/me/XP), MacOS 8 and 9, MacOS X, and Linux systems. A complete documentation is written for all the programs in the package and is part of the package. The author of this package is Joseph Felsenstein, Professor in the Department of Genome Sciences and the Department of Biology at the University of Washington, Seattle. Methods(implemented by each program) that are available in the package include parsimony, distance matrix, and likelihood methods, including bootstrapping and consensus trees. Data types that can be handled include molecular sequences, gene frequencies, restriction sites and fragments, distance matrices, and discrete characters. Each program is controlled through a menu, which asks the users which options they want to set, and allows them to start the computation. The data is read into the program from a text file, which the user can prepare using any word processor or text editor (but it is important that this text file not be in the special format of that word processor -- it should instead be in flat ASCII or Text Only format). Some sequence analysis programs such as the ClustalW alignment program can write data files in the PHYLIP format. Most of the programs look for the data in a file called infile -- if they do not find this file they then ask the user to type in the file name of the data file. Output is written onto files with names like outfile and outtree. Trees written onto outtree are in the Newick format, an informal standard agreed to in 1986 by authors of a number of major phylogeny packages. ## Phylip programs # Notes - ↑ Jump up to: 1.0 1.1 1.2 "PHYLIP general information page". Retrieved March 24, 2006..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} - ↑ Joseph Felsenstein (August, 2003). Inferring Phylogenies. sinauer associates. ISBN 0-87893-177-5. Check date values in: \|date= (help) - ↑ "PHYLIP package documentation mirror site". Retrieved March 24, 2006.	PHYLIP PHYLIP is a free Computational phylogenetics package of programs for inferring evolutionary trees (phylogenies). The name is an acronym for PHYLogeny Inference Package. It consists of 35 portable programs, i.e. The source code is written in C and precompiled executables are available for Windows (95/98/NT/2000/me/XP), MacOS 8 and 9, MacOS X, and Linux systems.[1] A complete documentation is written for all the programs in the package and is part of the package. The author of this package is Joseph Felsenstein, Professor in the Department of Genome Sciences and the Department of Biology at the University of Washington, Seattle.[2] Methods(implemented by each program) that are available in the package include parsimony, distance matrix, and likelihood methods, including bootstrapping and consensus trees. Data types that can be handled include molecular sequences, gene frequencies, restriction sites and fragments, distance matrices, and discrete characters. [1] Each program is controlled through a menu, which asks the users which options they want to set, and allows them to start the computation. The data is read into the program from a text file, which the user can prepare using any word processor or text editor (but it is important that this text file not be in the special format of that word processor -- it should instead be in flat ASCII or Text Only format). Some sequence analysis programs such as the ClustalW alignment program can write data files in the PHYLIP format. Most of the programs look for the data in a file called infile -- if they do not find this file they then ask the user to type in the file name of the data file. [1] Output is written onto files with names like outfile and outtree. Trees written onto outtree are in the Newick format, an informal standard agreed to in 1986 by authors of a number of major phylogeny packages. ## Phylip programs # Notes - ↑ Jump up to: 1.0 1.1 1.2 "PHYLIP general information page". Retrieved March 24, 2006..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} - ↑ Joseph Felsenstein (August, 2003). Inferring Phylogenies. sinauer associates. ISBN 0-87893-177-5. Check date values in: \|date= (help) - ↑ "PHYLIP package documentation mirror site". Retrieved March 24, 2006. # External links - Phylogeny Programs List: A large list of phylogeny packages with details about each software. Current count at 263. - Evolutionary trees from DNA sequences: a maximum likelihood approach.: Felsenstein J. Evolutionary trees from DNA sequences: a maximum likelihood approach. J Mol Evol. 1981;17:368–376. Template:WikiDoc Sources	https://www.wikidoc.org/index.php/PHYLIP
a07e53559977af3079ddaa775e734aa59e99d775	wikidoc	PI4K2A	PI4K2A Phosphatidylinositol 4-kinase 2-alpha is an enzyme that in humans is encoded by the PI4K2A gene. # Classification This gene encodes a phosphatidylinositol 4-kinase which catalyzes phosphorylation of phosphatidylinositol at the D-4 position, yielding phosphatidylinositol 4-phosphate (PI4P). Besides the fact, that PI4P serves as a precursor for other important phosphoinositides, such as phosphatidylinositol 4,5-bisphosphate, PI4P is an essential molecule in the cellular signaling and trafficking especially in the Golgi apparatus and the trans Golgi network. Phosphatidylinositol 4-kinases are evolutionary conserved among eukaryotes and include four human isoforms - phosphatidylinositol 4-kinase alpha (PI4KA) - phosphatidylinositol 4-kinase beta (PI4KB) - phosphatidylinositol 4-kinase 2-alpha (PI4K2A) - phosphatidylinositol 4-kinase 2-beta (PI4K2B) # Function Phosphatidylinositol 4-kinase 2-alpha (PI4K2A) is the most abundant phosphatidylinositol 4-kinase in human cells and is responsible for the synthesis of approximately 50% of the total PI4P within the cell. PI4K2A is associated mainly with the membranes of the trans Golgi network and early and late endosomes; its membrane association is achieved by a heavy palmitoylation within a specific cysteine-rich motif. Besides the synthesis of phosphatidylinositol 4,5-bisphosphate, PI4K2A is involved in various cell processes including membrane trafficking, regulation of endosomal sorting promoting target protein recruitment to endosomes or trans Golgi network, or signal transduction. Particularly, it regulates e.g. targeting of clathrin adaptor complexes to the Golgi apparatus, EGFR signaling, or the Wnt signaling pathway. # Clinical significance Dysfunction of PI4K2A may contribute to tumour growth, spastic paraplegia, Gaucher's disease, or Alzheimer's disease. # Structure PI4K2A is composed of a proline-rich N-terminal region and a kinase domain located C-terminally. The proline-rich N-terminal region contains physiologically important binding sites for a ubiquitin ligase Itch and clathrin adaptor complex 3, but is likely disordered and dispensable for the kinase activity. The kinase domain can be divided into N-terminal and C-terminal lobes with the ATP binding groove and putative phosphatidylinositol binding pocket in between. The C-lobe of the kinase domain contains an additional lateral hydrophobic pocket with no distinct function assigned yet.	PI4K2A Phosphatidylinositol 4-kinase 2-alpha is an enzyme that in humans is encoded by the PI4K2A gene.[1][2][3] # Classification This gene encodes a phosphatidylinositol 4-kinase which catalyzes phosphorylation of phosphatidylinositol at the D-4 position, yielding phosphatidylinositol 4-phosphate (PI4P). Besides the fact, that PI4P serves as a precursor for other important phosphoinositides, such as phosphatidylinositol 4,5-bisphosphate, PI4P is an essential molecule in the cellular signaling and trafficking especially in the Golgi apparatus and the trans Golgi network. Phosphatidylinositol 4-kinases are evolutionary conserved among eukaryotes and include four human isoforms - phosphatidylinositol 4-kinase alpha (PI4KA) - phosphatidylinositol 4-kinase beta (PI4KB) - phosphatidylinositol 4-kinase 2-alpha (PI4K2A) - phosphatidylinositol 4-kinase 2-beta (PI4K2B) # Function Phosphatidylinositol 4-kinase 2-alpha (PI4K2A) is the most abundant phosphatidylinositol 4-kinase in human cells and is responsible for the synthesis of approximately 50% of the total PI4P within the cell. PI4K2A is associated mainly with the membranes of the trans Golgi network and early and late endosomes;[4] its membrane association is achieved by a heavy palmitoylation within a specific cysteine-rich motif.[5] Besides the synthesis of phosphatidylinositol 4,5-bisphosphate, PI4K2A is involved in various cell processes including membrane trafficking, regulation of endosomal sorting promoting target protein recruitment to endosomes or trans Golgi network, or signal transduction. Particularly, it regulates e.g. targeting of clathrin adaptor complexes to the Golgi apparatus,[6] EGFR signaling,[7] or the Wnt signaling pathway.[8] # Clinical significance Dysfunction of PI4K2A may contribute to tumour growth,[9] spastic paraplegia,[10] Gaucher's disease,[11] or Alzheimer's disease.[12] # Structure PI4K2A is composed of a proline-rich N-terminal region and a kinase domain located C-terminally. The proline-rich N-terminal region contains physiologically important binding sites for a ubiquitin ligase Itch [13] and clathrin adaptor complex 3,[14] but is likely disordered and dispensable for the kinase activity.[15] The kinase domain can be divided into N-terminal and C-terminal lobes with the ATP binding groove and putative phosphatidylinositol binding pocket in between. The C-lobe of the kinase domain contains an additional lateral hydrophobic pocket with no distinct function assigned yet.[16][17]	https://www.wikidoc.org/index.php/PI4K2A
47a37c5eddc4c546af09b7cb9dc22db7bf9f2fea	wikidoc	PIEZO1	PIEZO1 Piezo1 is a mechanosensitive ion channel protein that in humans is encoded by the gene PIEZO1. Piezo1 and its close homolog piezo2 were cloned in 2010, using an siRNA-based screen for mechanosensitive ion channels. # Structure and function PIEZO1 (this gene) and PIEZO2 share 47% identity with each other and they have no similarity to any other protein and contain no known protein domains. They are predicted to have 24-36 transmembrane domains, depending on the prediction algorithm used. In the original publication the authors were careful not to call the piezo proteins ion channels, but a more recent study by the same lab convincingly demonstrated that indeed piezo1 is the pore forming subunit of a mechanosensitive channel. # Tissue distribution Piezo1 is expressed in the lungs, bladder and skin, where mechanosensation has important biological roles. Unlike Piezo2 which is highly expressed in sensory dorsal root ganglia, piezo1 is not expressed in sensory neurons. # Clinical significance Piezo1 is also found in red blood cells, and gain of function mutations in the channels are associated with hereditary xerocytosis or stomatocytosis. Piezo1 channels are pivotal integrators in vascular biology. An allele of Piezo1, E756del, results in a gain-of-function mutation, resulting in dehydrated RBCs and conveying resistance to Plasmodium. This allele has been demonstrated in vitro to prevent cerebral malaria infection. # Ligands - Yoda1 (small molecule agonist)	PIEZO1 Piezo1 is a mechanosensitive ion channel protein that in humans is encoded by the gene PIEZO1. Piezo1 and its close homolog piezo2 were cloned in 2010, using an siRNA-based screen for mechanosensitive ion channels.[1] # Structure and function PIEZO1 (this gene) and PIEZO2 share 47% identity with each other and they have no similarity to any other protein and contain no known protein domains. They are predicted to have 24-36 transmembrane domains, depending on the prediction algorithm used. In the original publication the authors were careful not to call the piezo proteins ion channels, but a more recent study by the same lab convincingly demonstrated that indeed piezo1 is the pore forming subunit of a mechanosensitive channel.[2] # Tissue distribution Piezo1 is expressed in the lungs, bladder and skin, where mechanosensation has important biological roles. Unlike Piezo2 which is highly expressed in sensory dorsal root ganglia, piezo1 is not expressed in sensory neurons.[1] # Clinical significance Piezo1 is also found in red blood cells, and gain of function mutations in the channels are associated with hereditary xerocytosis or stomatocytosis.[3][4][5] Piezo1 channels are pivotal integrators in vascular biology.[6] An allele of Piezo1, E756del, results in a gain-of-function mutation, resulting in dehydrated RBCs and conveying resistance to Plasmodium. This allele has been demonstrated in vitro to prevent cerebral malaria infection. [7] # Ligands - Yoda1 [8] (small molecule agonist)	https://www.wikidoc.org/index.php/PIEZO1
96aead9796a974186ec31134bc5ea3ae3ee11fd5	wikidoc	PIEZO2	PIEZO2 Piezo-type mechanosensitive ion channel component 2 is a protein that in humans is encoded by the PIEZO2 gene. # Function Piezos are large transmembrane proteins conserved among various species, all having between 24 and 36 predicted transmembrane domains. 'Piezo' comes from the Greek 'piesi,' meaning 'pressure.' The PIEZO2 protein has a role in rapidly adapting mechanically activated (MA) currents in somatosensory neurons. # Pathology - Gain-of-function mutations in the mechanically activated ion channel PIEZO2 cause a subtype of Distal Arthrogryposis. - Recent studies show that the congenital atrophy in PIEZO2 leads to not having self perception of extremities, and so the distortion in the response to touch (where the response was linked to an emotional response rather than a physical one). It was performed with two patients who would not be able to attempt to coordinate their movements without visually doing it, nor could they know where their extremities were at. - PIEZO2 mutations link Gordon syndrome (distal arthrogryposis type 3), Marden-Walker syndrome and Arthrogryposis (Distal Arthrogryposis Type 5).	PIEZO2 Piezo-type mechanosensitive ion channel component 2 is a protein that in humans is encoded by the PIEZO2 gene.[1] # Function Piezos are large transmembrane proteins conserved among various species, all having between 24 and 36 predicted transmembrane domains. 'Piezo' comes from the Greek 'piesi,' meaning 'pressure.' The PIEZO2 protein has a role in rapidly adapting mechanically activated (MA) currents in somatosensory neurons.[2] # Pathology - Gain-of-function mutations in the mechanically activated ion channel PIEZO2 cause a subtype of Distal Arthrogryposis.[3] - Recent studies show that the congenital atrophy in PIEZO2 leads to not having self perception of extremities, and so the distortion in the response to touch (where the response was linked to an emotional response rather than a physical one). It was performed with two patients who would not be able to attempt to coordinate their movements without visually doing it, nor could they know where their extremities were at. - PIEZO2 mutations link Gordon syndrome (distal arthrogryposis type 3), Marden-Walker syndrome and Arthrogryposis (Distal Arthrogryposis Type 5).[4]	https://www.wikidoc.org/index.php/PIEZO2
3b3af6a486dc101cc561b0dc984810384ad9f8ac	wikidoc	PIK3R1	PIK3R1 Phosphatidylinositol 3-kinase regulatory subunit alpha is an enzyme that in humans is encoded by the PIK3R1 gene. # Function Phosphatidylinositol 3-kinase phosphorylates the inositol ring of phosphatidylinositol at the 3-prime position. The enzyme comprises a 110 kD catalytic subunit and a regulatory subunit of either 85, 55, or 50 kD. This gene encodes the 85 kD regulatory subunit. Phosphatidylinositol 3-kinase plays an important role in the metabolic actions of insulin, and a mutation in this gene has been associated with insulin resistance. Alternative splicing of this gene results in three transcript variants encoding different isoforms. # Clinical significance Mutations in PIK3R1 are implicated in cases of breast cancer . Mutations in PIK3R1 are associated to SHORT syndrome . # Interactions PIK3R1 has been shown to interact with: - ADAM12, - BCAR1, - CBLB, - CD117, - CD28, - CD7, - CENTG1, - CBL, - EPHA2, - EPOR, - ERBB3, - EZR, - FCGR2A, - GAB1, - GAB2, - Grb2, - HRAS, - IRS1 - IRS2, - IL1R1, - JAK2, - KHDRBS1, - LTK, - LAT, - LCP2, - PIK3CD, - PTK2, - SHB, - TUBA1B, - TYRO3, - VAV1, and - WAS.	PIK3R1 Phosphatidylinositol 3-kinase regulatory subunit alpha is an enzyme that in humans is encoded by the PIK3R1 gene.[1] # Function Phosphatidylinositol 3-kinase phosphorylates the inositol ring of phosphatidylinositol at the 3-prime position. The enzyme comprises a 110 kD catalytic subunit and a regulatory subunit of either 85, 55, or 50 kD. This gene encodes the 85 kD regulatory subunit. Phosphatidylinositol 3-kinase plays an important role in the metabolic actions of insulin, and a mutation in this gene has been associated with insulin resistance. Alternative splicing of this gene results in three transcript variants encoding different isoforms.[2] # Clinical significance Mutations in PIK3R1 are implicated in cases of breast cancer .[3] Mutations in PIK3R1 are associated to SHORT syndrome .[4] # Interactions PIK3R1 has been shown to interact with: - ADAM12,[5] - BCAR1,[6] - CBLB,[7][8] - CD117,[9][10][11] - CD28,[12] - CD7,[13][14] - CENTG1,[15] - CBL,[16][17][18] - EPHA2,[19] - EPOR,[20][21] - ERBB3,[22][23] - EZR,[24] - FCGR2A,[25][26] - GAB1,[27][28][29] - GAB2,[30][31] - Grb2,[32][33] - HRAS,[34][35] - IRS1[36][37][38][39] - IRS2,[36][40][41][42] - IL1R1,[43] - JAK2,[44] - KHDRBS1,[45][46] - LTK,[47][48] - LAT,[49] - LCP2,[50] - PIK3CD,[51] - PTK2,[52] - SHB,[53] - TUBA1B,[54] - TYRO3,[55] - VAV1,[20][27] and - WAS.[56]	https://www.wikidoc.org/index.php/PIK3R1
64375892f5803017ee9dd6e5e23dcd6a471e0beb	wikidoc	PITRM1	PITRM1 Pitrilysin metallopeptidase 1 also known as presequence protease, mitochondrial (PreP) and metalloprotease 1 (MTP-1) is an enzyme that in humans is encoded by the PITRM1 gene. It is also sometimes called metalloprotease 1 (MP1).PreP facilitates proteostasis by utilizing an ~13300-A(3) catalytic chamber to degrade toxic peptides, including mitochondrial presequences and β-amyloid. Deficiency of PreP is found associated with Alzheimer’s disease. Reduced levels of PreP via RNAi mediated knockdown have been shown to lead to defective maturation of the protein Frataxin. # Structure ## Gene The PITRM1 gene is located at chromosome 10q15.2, consisting of 28 exons. ## Protein PreP is a 117 kDa M16C enzyme that is widely expressed in human tissues. PreP is composed of PreP-N (aa 33-509) and PreP-C (aa 576-1037) domains, which are connected by an extended helical hairpin (aa 510-575). Its structure demonstrates that substrate selection by size-exclusion is a conserved mechanism in M16C proteases. # Function PreP is an Zn2+-dependent and ATP-independent metalloprotease, it doesn’t select substrates on the basis of post-translational modifications or embedded degradation tags. Instead, it uses a negatively charged catalytic chamber to engulf substrates peptides of up to ~65 residues while excluding larger, folded proteins. It primarily localizes to the mitochondrial matrix, and cuts a range of peptides into recyclable fragments. The substrates of PreP are vital to proteostasis, as they can insert to mitochondrial membranes, disrupting electrical potential and uncoupling respiration. Thus deletion of PRTRM1 leads to a delayed growth phenotype. Notabley, PreP degrades several functionally relevant Aβ species, the aggregates of which are toxic to the neuron and play a key role in AD pathogenesis. # Clinical significance PreP is the Aβ-degrading protease in mitochondria. Immune-depletion of PreP in brain mitochondria prevents degradation of mitochondrial Aβ, and PreP activity is found diminished in AD patients. It has been reported that the loss of PreP activity is due to methionine oxidation and this study provides a rational basis for therapeutic intervention in conditions characterized by excessive oxidation of PreP. A recent study also suggests that PreP regulates islet amyloid polypeptide in beta cells. Two siblings carrying a homozygous PITRM1 missense mutation (c.548G>A, p.Arg183Gln) were reported to be associated with an autosomal recessive, slowly progressive syndrome. Clinical features include mental retardation, spinocerebellar ataxia, cognitive decline and psychosis. A mouse model hemizygous for PITRM1 displayed progressive ataxia which was suggested to be linked to brain degenerative lesions, including accumulation of Aβ‐positive amyloid deposits. Recently, two brothers from a consanguineous family presenting with childhood-onset recessive cerebellar pathology were shown to carry a homozygous mutation in PITRM1 (c.2795C>T, p.T931M). This mutation resulted in 95% reduction in PITRM1 protein. PITRM1 knockdown was shown to lead to reduced levels of mature Frataxin protein, a protein that when deficient causes Friedreich's ataxia, and may be implicated in pathology in patients carrying PITRM1 mutations. # Interactions PITRM1 has been shown to interact with the following proteins: CCL22, CGB2, DDX41, DEFB104A, HDHD3, MRPL12, NDUFV2, PRDX6, PRKCSH, RARS2, RIF1, SUCLG2, TEKT3, TERF2, and VAPB. # Model organisms Model organisms have been used in the study of PITRM1 function. A conditional knockout mouse line called Pitrm1tm1a(KOMP)Wtsi was generated at the Wellcome Trust Sanger Institute. Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion. Additional screens performed: - In-depth immunological phenotyping	PITRM1 Pitrilysin metallopeptidase 1 also known as presequence protease, mitochondrial (PreP) and metalloprotease 1 (MTP-1) is an enzyme that in humans is encoded by the PITRM1 gene.[1][2][3] It is also sometimes called metalloprotease 1 (MP1).PreP facilitates proteostasis by utilizing an ~13300-A(3) catalytic chamber to degrade toxic peptides, including mitochondrial presequences and β-amyloid.[4] Deficiency of PreP is found associated with Alzheimer’s disease. Reduced levels of PreP via RNAi mediated knockdown have been shown to lead to defective maturation of the protein Frataxin.[5] # Structure ## Gene The PITRM1 gene is located at chromosome 10q15.2, consisting of 28 exons. ## Protein PreP is a 117 kDa M16C enzyme that is widely expressed in human tissues.[6] PreP is composed of PreP-N (aa 33-509) and PreP-C (aa 576-1037) domains, which are connected by an extended helical hairpin (aa 510-575). Its structure demonstrates that substrate selection by size-exclusion is a conserved mechanism in M16C proteases.[4] # Function PreP is an Zn2+-dependent and ATP-independent metalloprotease, it doesn’t select substrates on the basis of post-translational modifications or embedded degradation tags.[7][8][9] Instead, it uses a negatively charged catalytic chamber to engulf substrates peptides of up to ~65 residues while excluding larger, folded proteins.[10][11] It primarily localizes to the mitochondrial matrix, and cuts a range of peptides into recyclable fragments.[12][13] The substrates of PreP are vital to proteostasis, as they can insert to mitochondrial membranes, disrupting electrical potential and uncoupling respiration.[14][15] Thus deletion of PRTRM1 leads to a delayed growth phenotype.[16][17] Notabley, PreP degrades several functionally relevant Aβ species, the aggregates of which are toxic to the neuron and play a key role in AD pathogenesis.[18][10][19] # Clinical significance PreP is the Aβ-degrading protease in mitochondria. Immune-depletion of PreP in brain mitochondria prevents degradation of mitochondrial Aβ, and PreP activity is found diminished in AD patients.[4] It has been reported that the loss of PreP activity is due to methionine oxidation and this study provides a rational basis for therapeutic intervention in conditions characterized by excessive oxidation of PreP.[20] A recent study also suggests that PreP regulates islet amyloid polypeptide in beta cells.[21] Two siblings carrying a homozygous PITRM1 missense mutation (c.548G>A, p.Arg183Gln) were reported to be associated with an autosomal recessive, slowly progressive syndrome. Clinical features include mental retardation, spinocerebellar ataxia, cognitive decline and psychosis.[22] A mouse model hemizygous for PITRM1 displayed progressive ataxia which was suggested to be linked to brain degenerative lesions, including accumulation of Aβ‐positive amyloid deposits. Recently, two brothers from a consanguineous family presenting with childhood-onset recessive cerebellar pathology were shown to carry a homozygous mutation in PITRM1 (c.2795C>T, p.T931M). This mutation resulted in 95% reduction in PITRM1 protein.[23] PITRM1 knockdown was shown to lead to reduced levels of mature Frataxin protein,[24] a protein that when deficient causes Friedreich's ataxia, and may be implicated in pathology in patients carrying PITRM1 mutations. # Interactions PITRM1 has been shown to interact with the following proteins: CCL22, CGB2, DDX41, DEFB104A, HDHD3, MRPL12, NDUFV2, PRDX6, PRKCSH, RARS2, RIF1, SUCLG2, TEKT3, TERF2, and VAPB.[25] # Model organisms Model organisms have been used in the study of PITRM1 function. A conditional knockout mouse line called Pitrm1tm1a(KOMP)Wtsi was generated at the Wellcome Trust Sanger Institute.[26] Male and female animals underwent a standardized phenotypic screen[27] to determine the effects of deletion.[28][29][30][31] Additional screens performed: - In-depth immunological phenotyping[32]	https://www.wikidoc.org/index.php/PITRM1
a0cb243ef9f0728e49801b91202e23e3445be9d0	wikidoc	PLA2G6	PLA2G6 85 kDa calcium-independent phospholipase A2, also known as 85/88 kDa calcium-independent phospholipase A2, Group VI phospholipase A2, Intracellular membrane-associated calcium-independent phospholipase A2 beta, or Patatin-like phospholipase domain-containing protein 9 is an enzyme that in humans is encoded by the PLA2G6 gene. # Structure The PLA2G6 gene is located on the p arm of chromosome 22 at position 13.1 and it spans 80,605 base pairs. The PLA2G6 gene produces an 18.6 kDa protein composed of 166 amino acids. The resulting protein's structure has been shown to contain a lipase motif and 8 ankyrin repeats. Different from rodent PLA2G6, which is known to share 90% overall amino acid sequence identity with that of the humans, the human PLA2G6 protein contains a 54-residue insertion which codes for a proline-rich region. This insertion has been shown to disrupt the last putative ankyrin repeat, as well as function as a linker region that segregates the N-terminal protein-binding domain from the C-terminal catalytic domain. # Function The PLA2G6 gene encodes for a phospholipase A2 enzyme, which is a subclass of enzyme that catalyzes the release of fatty acids from phospholipids. This type of enzyme is responsible for breaking down (metabolizing) phospholipids. Phospholipid metabolism is essential for many body processes, including helping to maintain the integrity of the cell membrane. Specifically, the A2 phospholipase produced from the PLA2G6 gene, sometimes called PLA2 group VI, helps to regulate the levels of a compound called phosphatidylcholine, which is abundant in the cell membrane. The encoded protein may also play a role in phospholipid remodelling, arachidonic acid release, nitric oxide-induced or vasopressin-induced arachidonic acid release and in leukotriene and prostaglandin synthesis, Fas receptor-mediated apoptosis, and transmembrane ion flux in glucose-stimulated B-cells. It addition, it has a role in cardiolipin (CL) deacylation, and is required for both speed and directionality of monocyte MCP1/CCL2-induced chemotaxis through regulation of F-actin polymerization at the pseudopods. Isoform ankyrin-iPLA2-1 and isoform ankyrin-iPLA2-2, which lack the catalytic domain, are probably involved in the negative regulation of PLA2G6 activity. Several transcript variants encoding multiple isoforms have been described, but the full-length nature of only two of them have been determined to date. # Catalytic activity Phosphatidylcholine + H2O = 1-acylglycerophosphocholine + a carboxylate. # Model organisms Model organisms have been used in the study of PLA2G6 function. A conditional knockout mouse line called Pla2g6tm1a(EUCOMM)Wtsi was generated at the Wellcome Trust Sanger Institute. Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion. Additional screens performed: - In-depth immunological phenotyping. # Clinical significance Mutations in PLA2G6 has been shown to result in mitochondrial deficiencies and associated disorders, including Neurodegeneration with brain iron accumulation 2B (NBIA2B), Neurodegeneration with brain iron accumulation 2A (NBIA2A), Parkinson disease 14 (PARK14), and hereditary spastic paraplegia. ## Neurodegeneration with brain iron accumulation 2B (NBIA2B) Neurodegeneration with brain iron accumulation 2B (NBIA2B) is a neurodegenerative disorder associated with iron accumulation in the brain, primarily in the basal ganglia. It is characterized by progressive extrapyramidal dysfunction leading to rigidity, dystonia, dysarthria and sensorimotor impairment. ## Neurodegeneration\|Neurodegeneration with brain iron accumulation 2A (NBIA2A) Neurodegeneration with brain iron accumulation 2A (NBIA2A) is a neurodegenerative disease characterized by pathologic axonal swelling and spheroid bodies in the central nervous system. Onset is within the first 2 years of life with death by age 10 years. ## Parkinson disease 14 (PARK14) Parkinson disease 14 (PARK14) is an adult-onset progressive neurodegenerative disorder characterized by parkinsonism, dystonia, severe cognitive decline, cerebral and cerebellar atrophy and absent iron in the basal ganglia on magnetic resonance imaging. ## Hereditary spastic paraplegia Hereditary spastic paraplegias are a diverse class of hereditary degenerative spinal cord disorders characterized by a slow, gradual, progressive weakness and spasticity (stiffness) of the legs. Initial symptoms may include difficulty with balance, weakness and stiffness in the legs, muscle spasms, and dragging the toes when walking. In some forms of the disorder, bladder symptoms (such as incontinence) may appear, or the weakness and stiffness may spread to other parts of the body. Rate of progression and the severity of symptoms are quite variable. # Interactions PLA2G6 has been shown to have Protein-protein interactions with the following. - BAG3 - ARF1 - CALM1 - HNRNPL	PLA2G6 85 kDa calcium-independent phospholipase A2, also known as 85/88 kDa calcium-independent phospholipase A2, Group VI phospholipase A2, Intracellular membrane-associated calcium-independent phospholipase A2 beta, or Patatin-like phospholipase domain-containing protein 9 is an enzyme that in humans is encoded by the PLA2G6 gene.[1][2][3][4][5][6] # Structure The PLA2G6 gene is located on the p arm of chromosome 22 at position 13.1 and it spans 80,605 base pairs.[4] The PLA2G6 gene produces an 18.6 kDa protein composed of 166 amino acids.[7][8] The resulting protein's structure has been shown to contain a lipase motif and 8 ankyrin repeats.[1] Different from rodent PLA2G6, which is known to share 90% overall amino acid sequence identity with that of the humans, the human PLA2G6 protein contains a 54-residue insertion which codes for a proline-rich region. This insertion has been shown to disrupt the last putative ankyrin repeat, as well as function as a linker region that segregates the N-terminal protein-binding domain from the C-terminal catalytic domain.[1][9] # Function The PLA2G6 gene encodes for a phospholipase A2 enzyme, which is a subclass of enzyme that catalyzes the release of fatty acids from phospholipids.[4] This type of enzyme is responsible for breaking down (metabolizing) phospholipids. Phospholipid metabolism is essential for many body processes, including helping to maintain the integrity of the cell membrane. Specifically, the A2 phospholipase produced from the PLA2G6 gene, sometimes called PLA2 group VI, helps to regulate the levels of a compound called phosphatidylcholine, which is abundant in the cell membrane.[10] The encoded protein may also play a role in phospholipid remodelling, arachidonic acid release, nitric oxide-induced or vasopressin-induced arachidonic acid release and in leukotriene and prostaglandin synthesis, Fas receptor-mediated apoptosis, and transmembrane ion flux in glucose-stimulated B-cells.[4][5] It addition, it has a role in cardiolipin (CL) deacylation, and is required for both speed and directionality of monocyte MCP1/CCL2-induced chemotaxis through regulation of F-actin polymerization at the pseudopods. Isoform ankyrin-iPLA2-1 and isoform ankyrin-iPLA2-2, which lack the catalytic domain, are probably involved in the negative regulation of PLA2G6 activity.[5] Several transcript variants encoding multiple isoforms have been described, but the full-length nature of only two of them have been determined to date.[4] # Catalytic activity Phosphatidylcholine + H2O = 1-acylglycerophosphocholine + a carboxylate.[6][5] # Model organisms Model organisms have been used in the study of PLA2G6 function. A conditional knockout mouse line called Pla2g6tm1a(EUCOMM)Wtsi was generated at the Wellcome Trust Sanger Institute.[11] Male and female animals underwent a standardized phenotypic screen[12] to determine the effects of deletion.[13][14][15][16] Additional screens performed: - In-depth immunological phenotyping.[17] # Clinical significance Mutations in PLA2G6 has been shown to result in mitochondrial deficiencies and associated disorders, including Neurodegeneration with brain iron accumulation 2B (NBIA2B), Neurodegeneration with brain iron accumulation 2A (NBIA2A), Parkinson disease 14 (PARK14), and hereditary spastic paraplegia.[18][5][6] ## Neurodegeneration with brain iron accumulation 2B (NBIA2B) Neurodegeneration with brain iron accumulation 2B (NBIA2B) is a neurodegenerative disorder associated with iron accumulation in the brain, primarily in the basal ganglia. It is characterized by progressive extrapyramidal dysfunction leading to rigidity, dystonia, dysarthria and sensorimotor impairment.[5][6] ## Neurodegeneration\|Neurodegeneration with brain iron accumulation 2A (NBIA2A) Neurodegeneration with brain iron accumulation 2A (NBIA2A) is a neurodegenerative disease characterized by pathologic axonal swelling and spheroid bodies in the central nervous system. Onset is within the first 2 years of life with death by age 10 years.[5][6] ## Parkinson disease 14 (PARK14) Parkinson disease 14 (PARK14) is an adult-onset progressive neurodegenerative disorder characterized by parkinsonism, dystonia, severe cognitive decline, cerebral and cerebellar atrophy and absent iron in the basal ganglia on magnetic resonance imaging.[5][6] ## Hereditary spastic paraplegia Hereditary spastic paraplegias are a diverse class of hereditary degenerative spinal cord disorders characterized by a slow, gradual, progressive weakness and spasticity (stiffness) of the legs. Initial symptoms may include difficulty with balance, weakness and stiffness in the legs, muscle spasms, and dragging the toes when walking. In some forms of the disorder, bladder symptoms (such as incontinence) may appear, or the weakness and stiffness may spread to other parts of the body. Rate of progression and the severity of symptoms are quite variable.[19] # Interactions PLA2G6 has been shown to have Protein-protein interactions with the following.[20][5] - BAG3 - ARF1 - CALM1 - HNRNPL	https://www.wikidoc.org/index.php/PLA2G6
ff258394beab30100c5c79990042500034deb515	wikidoc	PLAGL2	PLAGL2 Zinc finger protein PLAGL2 is a protein that in humans is encoded by the PLAGL2 gene. Zinc finger protein PLAGL2 is a zinc finger protein that recognizes DNA and/or RNA. The gene has seen in gliomas to suppress cellular differentiation and thus encourage cells to become more stem cell like. Such plasticity is seen in glioma cells, together with the ignorance to differentiation factors.	PLAGL2 Zinc finger protein PLAGL2 is a protein that in humans is encoded by the PLAGL2 gene.[1][2][3] Zinc finger protein PLAGL2 is a zinc finger protein that recognizes DNA and/or RNA.[3] The gene has seen in gliomas to suppress cellular differentiation and thus encourage cells to become more stem cell like. Such plasticity is seen in glioma cells, together with the ignorance to differentiation factors.[4]	https://www.wikidoc.org/index.php/PLAGL2
3978fdd3f19d796538d9dbcdd559ccf32049480a	wikidoc	PLSCR3	PLSCR3 Phospholipid scramblase 3 is an enzyme that in humans is encoded by the PLSCR3 gene (abbreviated to PLS3 in this section). Like the other phospholipid scramblase family members (PLS1, PLS2, PLS4), PLS3 is a type II plasma membrane protein that is rich in proline and integral in apoptosis, or programmed cell death. The regulation of apoptosis is critical for both cell development and tissue homeostasis Although phospholipid scramblase is thought to exist in all eukaryotic cells, PLS3 is a protein that is novel to the mitochondria. This is very important because mitochondria are central in the apoptotic cell pathway. This newly found member of the scramblase family is "responsible for phospholipid translocation between two lipid compartments," the inner mitochondrial membrane and the outer membrane. Further experimental evidence suggests that the mechanism and effectors of PLS3's enzymatic activity are rather nuanced. # Effect on mitochondrial cardiolipin Cardiolipin is a mitochondrion-specific phospholipid found in both the mitochondrial inner and outer membranes Many studies speculate that cardiolipin is a likely player in mitochondrial apoptosis. In a study done by R Lee et al., it was found that during apoptosis, cardiolipin in the outer membrane of the mitochondria increased from 10% to 30% saturation. Finding that cardiolipin concentration in the outer mitochondrial membrane increased during apoptosis (as well as knowing the function that PLS3 plays in mitochondrial apoptotic effects) clued Lee in to the fact that PLS3 may have effects on this cardiolipin membrane redistribution. Lee’s study looked into the consequences of cardiolipin redistribution in the mitochondria and found that cardiolipin plays a critical role in proteins that are involved with oxidative respiration (such as ATP synthase), which in turn affects ATP production. In Lee's experiment determining the effect of cardiolipin deprivation on cells, he studied an infected yeast mutant that lacked a cardiolipin creating enzyme, and found that although it was viable, the yeast was "moderately deficient in mitochondrial energy transforming machinery." It was subsequently deduced that PLS3 is an effector for the redistribution of cardiolipin from the inner to outer mitochondrial membrane. Thus, when PLS3 flips cardiolipin across the inner to outer membrane of the mitochondria, the oxidative phosphorylation induced is greatly disturbed. It was deduced experimentally that a lack of proper oxidative phosphorylation is directly linked with mitochondrial apoptosis. Thus, this PLS3-induced redistribution of cardiolipin during apoptosis has major effects on mitochondrial function. # Summary Although the results of the experiments above are very intriguing and shed light on what was once a mystery, there have been only a few experiments that have targeted PSL3. And, furthermore, in a majority of the experiments and studies that were reviewed, it is evident that there is some doubt in the experimental findings	PLSCR3 Phospholipid scramblase 3 is an enzyme that in humans is encoded by the PLSCR3 gene [1][2] (abbreviated to PLS3 in this section). Like the other phospholipid scramblase family members (PLS1, PLS2, PLS4), PLS3 is a type II plasma membrane protein that is rich in proline and integral in apoptosis, or programmed cell death. The regulation of apoptosis is critical for both cell development and tissue homeostasis [3] Although phospholipid scramblase is thought to exist in all eukaryotic cells, PLS3 is a protein that is novel to the mitochondria.[4] This is very important because mitochondria are central in the apoptotic cell pathway. This newly found member of the scramblase family is "responsible for phospholipid translocation between two lipid compartments," [3] the inner mitochondrial membrane and the outer membrane. Further experimental evidence suggests that the mechanism and effectors of PLS3's enzymatic activity are rather nuanced. # Effect on mitochondrial cardiolipin Cardiolipin is a mitochondrion-specific phospholipid found in both the mitochondrial inner and outer membranes[5] Many studies speculate that cardiolipin is a likely player in mitochondrial apoptosis. In a study done by R Lee et al., it was found that during apoptosis, cardiolipin in the outer membrane of the mitochondria increased from 10% to 30% saturation. Finding that cardiolipin concentration in the outer mitochondrial membrane increased during apoptosis (as well as knowing the function that PLS3 plays in mitochondrial apoptotic effects) clued Lee in to the fact that PLS3 may have effects on this cardiolipin membrane redistribution. Lee’s study looked into the consequences of cardiolipin redistribution in the mitochondria and found that cardiolipin plays a critical role in proteins that are involved with oxidative respiration (such as ATP synthase), which in turn affects ATP production. In Lee's experiment determining the effect of cardiolipin deprivation on cells, he studied an infected yeast mutant that lacked a cardiolipin creating enzyme, and found that although it was viable, the yeast was "moderately deficient in mitochondrial energy transforming machinery." It was subsequently deduced that PLS3 is an effector for the redistribution of cardiolipin from the inner to outer mitochondrial membrane. Thus, when PLS3 flips cardiolipin across the inner to outer membrane of the mitochondria, the oxidative phosphorylation induced is greatly disturbed. It was deduced experimentally that a lack of proper oxidative phosphorylation is directly linked with mitochondrial apoptosis. Thus, this PLS3-induced redistribution of cardiolipin during apoptosis has major effects on mitochondrial function. # Summary Although the results of the experiments above are very intriguing and shed light on what was once a mystery, there have been only a few experiments that have targeted PSL3. And, furthermore, in a majority of the experiments and studies that were reviewed, it is evident that there is some doubt in the experimental findings [6][7][8]	https://www.wikidoc.org/index.php/PLSCR3
ad6a2ed7c1c9d5e60b63c7ff369cc82bfbb44433	wikidoc	PLXNA2	PLXNA2 Plexin-A2 is a protein that in humans is coded by the PLXNA2 gene. This gene encodes a member of the plexin-A family of semaphorin co-receptors. Semaphorins are a large family of secreted or membrane-bound proteins that mediate repulsive effects on axon pathfinding during nervous system development. A subset of semaphorins are recognized by plexin-A/neuropilin transmembrane receptor complexes, triggering a cellular signal transduction cascade that leads to axon repulsion. This plexin-A family member is thought to transduce signals from semaphorin-3A and -3C. In some studies, the PLXNA2 gene is associated with schizophrenia. and anxiety.	PLXNA2 Plexin-A2 is a protein that in humans is coded by the PLXNA2 gene.[1][2] This gene encodes a member of the plexin-A family of semaphorin co-receptors. Semaphorins are a large family of secreted or membrane-bound proteins that mediate repulsive effects on axon pathfinding during nervous system development. A subset of semaphorins are recognized by plexin-A/neuropilin transmembrane receptor complexes, triggering a cellular signal transduction cascade that leads to axon repulsion. This plexin-A family member is thought to transduce signals from semaphorin-3A and -3C.[2] In some studies, the PLXNA2 gene is associated with schizophrenia.[3] and anxiety.[4]	https://www.wikidoc.org/index.php/PLXNA2
3367e38a4c10301be730ab97644130f42591f8dc	wikidoc	PLXNB1	PLXNB1 Plexin B1 is a protein of the plexin family that in humans is encoded by the PLXNB1 gene. # Function Within neural tissues, the plexin family serves as transmembrane receptors for Semaphorins. Outside of neural tissues, Plexin B1 is implicated in the control of cell migration. # Interactions PLXNB1 has been shown to interact with ARHGEF12, Rnd1 and ARHGEF11.	PLXNB1 Plexin B1 is a protein of the plexin family that in humans is encoded by the PLXNB1 gene.[1][2][3] # Function Within neural tissues, the plexin family serves as transmembrane receptors for Semaphorins.[4] Outside of neural tissues, Plexin B1 is implicated in the control of cell migration.[5] # Interactions PLXNB1 has been shown to interact with ARHGEF12,[6] Rnd1[7] and ARHGEF11.[6][7][8][9]	https://www.wikidoc.org/index.php/PLXNB1
7e13ab9c4739864fe70fce627f62591dd84678ed	wikidoc	PNPLA3	PNPLA3 Patatin-like phospholipase domain-containing protein 3 (PNPLA3) also known as adiponutrin (ADPN), acylglycerol O-acyltransferase or calcium-independent phospholipase A2-epsilon (iPLA2-epsilon) is an enzyme that in humans is encoded by the PNPLA3 gene. # Function Adiponutrin is a triacylglycerol lipase that mediates triacylglycerol hydrolysis in adipocytes. The encoded protein, which appears to be membrane bound, may be involved in the balance of energy usage/storage in adipocytes. # Genomics The gene is located on the long arm of chromosome 22 at band 13.31 (22q13.31). It lies on the Watson (plus) strand and is 40,750 bases in length. Upstream of the gene putaive binding sites for several transcription factors have been identified. These include PPAR-gamma, POU2F1, and POU2F2. If any of these transcriptions factors are actually involved in the regulation of this gene is not known at present. # Biochemistry The recommended name for the gene product is patatin-like phospholipase domain-containing protein 3. It is a Single-pass type II membrane protein and is a multifunctional enzyme with both triacylglycerol lipase and acylglycerol O-acyltransferase activities. It is involved in the triacylglycerol hydrolysis in adipocytes and may play a role in energy metabolism. The mature protein is 481 amino acids in length and the predicted molecular weight is 52.865 kiloDaltons (kDa). Two the isoforms have been described but the functional significance - if any - of these forms is not known. # Clinical relevance An association between alcoholic liver disease in caucasians and variations in this gene has been confirmed. Gut 2012;61:150-159 doi:10.1136/gutjnl-2011-301239, Genetic determinants of alcoholic liver disease, Felix Stickel,Jochen Hampe.	PNPLA3 Patatin-like phospholipase domain-containing protein 3 (PNPLA3) also known as adiponutrin (ADPN), acylglycerol O-acyltransferase or calcium-independent phospholipase A2-epsilon (iPLA2-epsilon) is an enzyme that in humans is encoded by the PNPLA3 gene.[1][2][3] # Function Adiponutrin is a triacylglycerol lipase that mediates triacylglycerol hydrolysis in adipocytes. The encoded protein, which appears to be membrane bound, may be involved in the balance of energy usage/storage in adipocytes.[3] # Genomics The gene is located on the long arm of chromosome 22 at band 13.31 (22q13.31). It lies on the Watson (plus) strand and is 40,750 bases in length. Upstream of the gene putaive binding sites for several transcription factors have been identified. These include PPAR-gamma, POU2F1, and POU2F2. If any of these transcriptions factors are actually involved in the regulation of this gene is not known at present. # Biochemistry The recommended name for the gene product is patatin-like phospholipase domain-containing protein 3. It is a Single-pass type II membrane protein and is a multifunctional enzyme with both triacylglycerol lipase and acylglycerol O-acyltransferase activities. It is involved in the triacylglycerol hydrolysis in adipocytes and may play a role in energy metabolism. The mature protein is 481 amino acids in length and the predicted molecular weight is 52.865 kiloDaltons (kDa). Two the isoforms have been described but the functional significance - if any - of these forms is not known. # Clinical relevance An association between alcoholic liver disease in caucasians and variations in this gene has been confirmed. Gut 2012;61:150-159 doi:10.1136/gutjnl-2011-301239, Genetic determinants of alcoholic liver disease, Felix Stickel,Jochen Hampe.	https://www.wikidoc.org/index.php/PNPLA3
db031ebae95b0e413dca7b7d1b8bee16a3b567fc	wikidoc	POLR1E	POLR1E DNA-directed RNA polymerase I subunit RPA49 is an enzyme that in humans is encoded by the POLR1E gene. # Model organisms Model organisms have been used in the study of POLR1E function. A conditional knockout mouse line, called Polr1etm1a(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. Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion. Twenty seven tests were carried out on mutant mice and two significant abnormalities were observed. No homozygous mutant embryos were identified during gestation, and therefore none survived until weaning. The remaining tests were carried out on heterozygous mutant adult mice; no additional significant abnormalities were observed in these animals. # Interactions POLR1E has been shown to interact with CD3EAP and POLR1C.	POLR1E DNA-directed RNA polymerase I subunit RPA49 is an enzyme that in humans is encoded by the POLR1E gene.[1][2] # Model organisms Model organisms have been used in the study of POLR1E function. A conditional knockout mouse line, called Polr1etm1a(KOMP)Wtsi[7][8] was generated as part of the International Knockout Mouse Consortium program—a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists.[9][10][11] Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion.[5][12] Twenty seven tests were carried out on mutant mice and two significant abnormalities were observed.[5] No homozygous mutant embryos were identified during gestation, and therefore none survived until weaning. The remaining tests were carried out on heterozygous mutant adult mice; no additional significant abnormalities were observed in these animals.[5] # Interactions POLR1E has been shown to interact with CD3EAP[13] and POLR1C.[14][13][15]	https://www.wikidoc.org/index.php/POLR1E
f83818858ee0b964978eb21a8cb302695a81d0a9	wikidoc	POLR2B	POLR2B DNA-directed RNA polymerase II subunit RPB2 is an enzyme that in humans is encoded by the POLR2B gene. This gene encodes the second largest subunit of RNA polymerase II, the polymerase responsible for synthesizing messenger RNA in eukaryotes. This subunit, in combination with at least two other polymerase subunits, forms a structure within the polymerase that maintains contact in the active site of the enzyme between the DNA template and the newly synthesized RNA. # Interactions POLR2B has been shown to interact with POLR2C, POLR2E, POLR2H and POLR2L.	POLR2B DNA-directed RNA polymerase II subunit RPB2 is an enzyme that in humans is encoded by the POLR2B gene.[1][2] This gene encodes the second largest subunit of RNA polymerase II, the polymerase responsible for synthesizing messenger RNA in eukaryotes. This subunit, in combination with at least two other polymerase subunits, forms a structure within the polymerase that maintains contact in the active site of the enzyme between the DNA template and the newly synthesized RNA.[3] # Interactions POLR2B has been shown to interact with POLR2C,[4] POLR2E,[4] POLR2H[4] and POLR2L.[4]	https://www.wikidoc.org/index.php/POLR2B
817d1a6b90c7a036730abed6e382fd97ee09b93c	wikidoc	POLR2E	POLR2E DNA-directed RNA polymerases I, II, and III subunit RPABC1 is a protein that in humans is encoded by the POLR2E gene. This gene encodes the fifth largest subunit of RNA polymerase II, the polymerase responsible for synthesizing messenger RNA in eukaryotes. This subunit is shared by the other two DNA-directed RNA polymerases and is present in two-fold molar excess over the other polymerase subunits. An interaction between this subunit and a hepatitis virus transactivating protein has been demonstrated, suggesting that interaction between transcriptional activators and the polymerase can occur through this subunit. A pseudogene is located on chromosome 11. # Interactions POLR2E has been shown to interact with TAF15, POLR2C, POLR2G, POLR2H, POLR2A, POLR2B, POLR2L and GTF2F2.	POLR2E DNA-directed RNA polymerases I, II, and III subunit RPABC1 is a protein that in humans is encoded by the POLR2E gene.[1] This gene encodes the fifth largest subunit of RNA polymerase II, the polymerase responsible for synthesizing messenger RNA in eukaryotes. This subunit is shared by the other two DNA-directed RNA polymerases and is present in two-fold molar excess over the other polymerase subunits. An interaction between this subunit and a hepatitis virus transactivating protein has been demonstrated, suggesting that interaction between transcriptional activators and the polymerase can occur through this subunit. A pseudogene is located on chromosome 11.[2] # Interactions POLR2E has been shown to interact with TAF15,[3] POLR2C,[4] POLR2G,[4] POLR2H,[4] POLR2A,[4] POLR2B,[4] POLR2L[4] and GTF2F2.[5]	https://www.wikidoc.org/index.php/POLR2E
577216ce34ce4940f7b438ad7edc0748b0e6c7f0	wikidoc	POLR2G	POLR2G DNA-directed RNA polymerase II subunit RPB7 is an enzyme that in humans is encoded by the POLR2G gene. This gene encodes the seventh largest subunit of RNA polymerase II, the polymerase responsible for synthesizing messenger RNA in eukaryotes. In yeast, the association of this subunit with the polymerase under suboptimal growth conditions indicates it may play a role in regulating polymerase function. # Interactions POLR2G has been shown to interact with TAF15, POLR2C, POLR2H and POLR2E.	POLR2G DNA-directed RNA polymerase II subunit RPB7 is an enzyme that in humans is encoded by the POLR2G gene.[1][2] This gene encodes the seventh largest subunit of RNA polymerase II, the polymerase responsible for synthesizing messenger RNA in eukaryotes. In yeast, the association of this subunit with the polymerase under suboptimal growth conditions indicates it may play a role in regulating polymerase function.[3] # Interactions POLR2G has been shown to interact with TAF15,[4] POLR2C,[5] POLR2H[5] and POLR2E.[5]	https://www.wikidoc.org/index.php/POLR2G
9967ab0cd85dc538eff1344b25aa3c487d277d1f	wikidoc	POLR2H	POLR2H DNA-directed RNA polymerases I, II, and III subunit RPABC3 is a protein that in humans is encoded by the POLR2H gene. This gene encodes one of the essential subunits of RNA polymerase II that is shared by the other two eukaryotic DNA-directed RNA polymerases, I and III. # Interactions POLR2H has been shown to interact with POLR2C, POLR2G, POLR2A, POLR2B and POLR2E.	POLR2H DNA-directed RNA polymerases I, II, and III subunit RPABC3 is a protein that in humans is encoded by the POLR2H gene. This gene encodes one of the essential subunits of RNA polymerase II that is shared by the other two eukaryotic DNA-directed RNA polymerases, I and III.[1] # Interactions POLR2H has been shown to interact with POLR2C,[2] POLR2G,[2] POLR2A,[2] POLR2B[2] and POLR2E.[2]	https://www.wikidoc.org/index.php/POLR2H
ff5093b917e4115e2029ff0c603f6fe2f9162647	wikidoc	POLR2L	POLR2L DNA-directed RNA polymerases I, II, and III subunit RPABC5 is a protein that in humans is encoded by the POLR2L gene. # Function This gene encodes a subunit of RNA polymerase II, the polymerase responsible for synthesizing messenger RNA in eukaryotes. The product of this gene contains four conserved cysteines characteristic of an atypical zinc-binding domain. Like its counterpart in yeast, this subunit may be shared by the other two DNA-directed RNA polymerases. # Interactions POLR2L has been shown to interact with POLR2C, POLR2A, POLR2B and POLR2E.	POLR2L DNA-directed RNA polymerases I, II, and III subunit RPABC5 is a protein that in humans is encoded by the POLR2L gene.[1] # Function This gene encodes a subunit of RNA polymerase II, the polymerase responsible for synthesizing messenger RNA in eukaryotes. The product of this gene contains four conserved cysteines characteristic of an atypical zinc-binding domain. Like its counterpart in yeast, this subunit may be shared by the other two DNA-directed RNA polymerases.[2] # Interactions POLR2L has been shown to interact with POLR2C,[3] POLR2A,[3] POLR2B[3] and POLR2E.[3]	https://www.wikidoc.org/index.php/POLR2L
417c8fdaa7decc4bfc5af15939bfa09c20e4ac70	wikidoc	POLR3E	POLR3E DNA-directed RNA polymerase III subunit RPC5 is an enzyme that in humans is encoded by the POLR3E gene. # Interactions POLR3E has been shown to interact with POLR3D. # Notes and references - ↑ Nagase T, Kikuno R, Ishikawa K, Hirosawa M, Ohara O (Sep 2000). "Prediction of the coding sequences of unidentified human genes. XVII. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro". DNA Res. 7 (2): 143–50. doi:10.1093/dnares/7.2.143. PMID 10819331..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} - ↑ Dong Z, Bell LR (Nov 1999). "SIN, a novel Drosophila protein that associates with the RNA binding protein sex-lethal". Gene. 237 (2): 421–8. doi:10.1016/S0378-1119(99)00303-0. PMID 10521666. - ↑ "Entrez Gene: POLR3E polymerase (RNA) III (DNA directed) polypeptide E (80kD)". - ↑ Hu, Ping; Wu Si; Sun Yuling; Yuan Chih-Chi; Kobayashi Ryuji; Myers Michael P; Nouria Hernandez (Nov 2002). "Characterization of Human RNA Polymerase III Identifies Orthologues for Saccharomyces cerevisiae RNA Polymerase III Subunits" (PDF). Mol. Cell. Biol. United States. 22 (22): 8044–55. doi:10.1128/MCB.22.22.8044-8055.2002. ISSN 0270-7306. PMC 134740. PMID 12391170. # Further reading - Jang KL, Collins MK, Latchman DS (1992). "The human immunodeficiency virus tat protein increases the transcription of human Alu repeated sequences by increasing the activity of the cellular transcription factor TFIIIC". J. Acquir. Immune Defic. Syndr. 5 (11): 1142–7. PMID 1403646. - Maruyama K, Sugano S (1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene. 138 (1–2): 171–4. doi:10.1016/0378-1119(94)90802-8. PMID 8125298. - Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, et al. (1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene. 200 (1–2): 149–56. doi:10.1016/S0378-1119(97)00411-3. PMID 9373149. - Hu P, Wu S, Sun Y, et al. (2002). "Characterization of Human RNA Polymerase III Identifies Orthologues for Saccharomyces cerevisiae RNA Polymerase III Subunits". Mol. Cell. Biol. 22 (22): 8044–55. doi:10.1128/MCB.22.22.8044-8055.2002. PMC 134740. PMID 12391170. - Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. Bibcode:2002PNAS...9916899M. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932. - Ota T, Suzuki Y, Nishikawa T, et al. (2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs". Nat. Genet. 36 (1): 40–5. doi:10.1038/ng1285. PMID 14702039. - Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The Status, Quality, and Expansion of the NIH Full-Length cDNA Project: The Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334.	POLR3E DNA-directed RNA polymerase III subunit RPC5 is an enzyme that in humans is encoded by the POLR3E gene.[1][2][3] # Interactions POLR3E has been shown to interact with POLR3D.[4] # Notes and references - ↑ Nagase T, Kikuno R, Ishikawa K, Hirosawa M, Ohara O (Sep 2000). "Prediction of the coding sequences of unidentified human genes. XVII. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro". DNA Res. 7 (2): 143–50. doi:10.1093/dnares/7.2.143. PMID 10819331..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} - ↑ Dong Z, Bell LR (Nov 1999). "SIN, a novel Drosophila protein that associates with the RNA binding protein sex-lethal". Gene. 237 (2): 421–8. doi:10.1016/S0378-1119(99)00303-0. PMID 10521666. - ↑ "Entrez Gene: POLR3E polymerase (RNA) III (DNA directed) polypeptide E (80kD)". - ↑ Hu, Ping; Wu Si; Sun Yuling; Yuan Chih-Chi; Kobayashi Ryuji; Myers Michael P; Nouria Hernandez (Nov 2002). "Characterization of Human RNA Polymerase III Identifies Orthologues for Saccharomyces cerevisiae RNA Polymerase III Subunits" (PDF). Mol. Cell. Biol. United States. 22 (22): 8044–55. doi:10.1128/MCB.22.22.8044-8055.2002. ISSN 0270-7306. PMC 134740. PMID 12391170. # Further reading - Jang KL, Collins MK, Latchman DS (1992). "The human immunodeficiency virus tat protein increases the transcription of human Alu repeated sequences by increasing the activity of the cellular transcription factor TFIIIC". J. Acquir. Immune Defic. Syndr. 5 (11): 1142–7. PMID 1403646. - Maruyama K, Sugano S (1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene. 138 (1–2): 171–4. doi:10.1016/0378-1119(94)90802-8. PMID 8125298. - Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, et al. (1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene. 200 (1–2): 149–56. doi:10.1016/S0378-1119(97)00411-3. PMID 9373149. - Hu P, Wu S, Sun Y, et al. (2002). "Characterization of Human RNA Polymerase III Identifies Orthologues for Saccharomyces cerevisiae RNA Polymerase III Subunits". Mol. Cell. Biol. 22 (22): 8044–55. doi:10.1128/MCB.22.22.8044-8055.2002. PMC 134740. PMID 12391170. - Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. Bibcode:2002PNAS...9916899M. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932. - Ota T, Suzuki Y, Nishikawa T, et al. (2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs". Nat. Genet. 36 (1): 40–5. doi:10.1038/ng1285. PMID 14702039. - Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The Status, Quality, and Expansion of the NIH Full-Length cDNA Project: The Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334.	https://www.wikidoc.org/index.php/POLR3E
d4beda06ef3087e21a05facc7c8f85d3349d3a8d	wikidoc	POLR3F	POLR3F DNA-directed RNA polymerase III subunit RPC6 is an enzyme that in humans is encoded by the POLR3F gene. # Function The protein encoded by this gene is one of more than a dozen subunits forming eukaryotic RNA polymerase III (RNA Pol III), which transcribes 5S ribosomal RNA and tRNA genes. This protein has been shown to bind both TFIIIB90 and TBP, two subunits of RNA polymerase III transcription initiation factor IIIB (TFIIIB). Unlike most of the other RNA Pol III subunits, the encoded protein is unique to this polymerase. # Model organisms Model organisms have been used in the study of POLR3F function. A conditional knockout mouse line called Polr3ftm1a(EUCOMM)Wtsi was generated at the Wellcome Trust Sanger Institute. Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion. Additional screens performed: - In-depth immunological phenotyping	POLR3F DNA-directed RNA polymerase III subunit RPC6 is an enzyme that in humans is encoded by the POLR3F gene.[1][2] # Function The protein encoded by this gene is one of more than a dozen subunits forming eukaryotic RNA polymerase III (RNA Pol III), which transcribes 5S ribosomal RNA and tRNA genes. This protein has been shown to bind both TFIIIB90 and TBP, two subunits of RNA polymerase III transcription initiation factor IIIB (TFIIIB). Unlike most of the other RNA Pol III subunits, the encoded protein is unique to this polymerase.[2] # Model organisms Model organisms have been used in the study of POLR3F function. A conditional knockout mouse line called Polr3ftm1a(EUCOMM)Wtsi was generated at the Wellcome Trust Sanger Institute.[3] Male and female animals underwent a standardized phenotypic screen[4] to determine the effects of deletion.[5][6][7][8] Additional screens performed: - In-depth immunological phenotyping[9]	https://www.wikidoc.org/index.php/POLR3F
2e75f7dd54128f783535d59a274589970435af46	wikidoc	POM121	POM121 Nuclear envelope pore membrane protein POM 121 is a protein that in humans is encoded by the POM121 gene. Alternatively spliced variants that encode different protein isoforms have been described but the full-length nature of only one has been determined. # Function The nuclear envelope creates distinct nuclear and cytoplasmic compartments in eukaryotic cells. It consists of two concentric membranes perforated by nuclear pores, large protein complexes that form aqueous channels to regulate the flow of macromolecules between the nucleus and the cytoplasm. These complexes are composed of at least 100 different polypeptide subunits, many of which belong to the nucleoporin family. This gene encodes a member of the FG-repeat-containing nucleoporins. The protein encoded by this gene is an integral membrane protein that localizes to the central spoke ring complex and participates in anchoring the nuclear pore complex to the nuclear envelope. Antibodies against this protein can be used to identify the nuclear envelope in immunofluorescence experiments.	POM121 Nuclear envelope pore membrane protein POM 121 is a protein that in humans is encoded by the POM121 gene.[1][2][3] Alternatively spliced variants that encode different protein isoforms have been described but the full-length nature of only one has been determined.[4] # Function The nuclear envelope creates distinct nuclear and cytoplasmic compartments in eukaryotic cells. It consists of two concentric membranes perforated by nuclear pores, large protein complexes that form aqueous channels to regulate the flow of macromolecules between the nucleus and the cytoplasm. These complexes are composed of at least 100 different polypeptide subunits, many of which belong to the nucleoporin family. This gene encodes a member of the FG-repeat-containing nucleoporins. The protein encoded by this gene is an integral membrane protein that localizes to the central spoke ring complex and participates in anchoring the nuclear pore complex to the nuclear envelope.[4] Antibodies against this protein can be used to identify the nuclear envelope in immunofluorescence experiments.[5]	https://www.wikidoc.org/index.php/POM121
90d75c3da4e9e5435562ac366ce1dd1eae5f2719	wikidoc	POPDC2	POPDC2 Popeye domain-containing protein 2 is a protein that in humans is encoded by the POPDC2 gene. # Structure This gene encodes a member of the POP family of proteins which contain three putative transmembrane domains. This membrane associated protein is predominantly expressed in skeletal and cardiac muscle. The Popeye domain, which is located in the cytoplasmic part of the protein displays limited sequence homology to other proteins, while sequence conservation amongst Popeye proteins is high and amounts to approximately 40%–60%. # Function The bacterial CAP or CRP proteins are the closest related non-Popdcproteins. CRP proteins function as cyclic nucleotide-regulated transcription factors that modulate the expression of genes encoding enzymes involved in carbohydrate metabolism. The cyclic AMP-binding domains of these proteins display approximately 25% identity and 60% similarity to the Popeye domain. Significant structural similarity is evident between the Popeye domain and cAMP binding domains of eukaryotic protein kinase A (PKA) and HCN channels. # Ligands The Popeye domain binds cyclic nucleotides and has a binding affinity (IC50) for cAMP of 120 nM, which is comparable to the affinities reported for PKA (100 nM) and HCN4 (240 nM). One of the interacting proteins is the two-pore potassium (K2P) channel TREK-1. In the presence of Popdc proteins, TREK-1 current is increased. This increase was based on an enhanced membrane representation of TREK-1, suggesting a modulation of channel trafficking by Popdc proteins. # Animal studies Genetic inactivation of Popdc2 in mice resulted in bradyarrhythmia, which is strictly stress-dependent. At rest a normal ECG was observed. Gene inactivation in the zebrafish also causes a cardiac arrhythmia phenotype and defective skeletal muscle development.	POPDC2 Popeye domain-containing protein 2 is a protein that in humans is encoded by the POPDC2 gene.[1][2] # Structure This gene encodes a member of the POP family of proteins which contain three putative transmembrane domains. This membrane associated protein is predominantly expressed in skeletal and cardiac muscle.[1] The Popeye domain, which is located in the cytoplasmic part of the protein displays limited sequence homology to other proteins, while sequence conservation amongst Popeye proteins is high and amounts to approximately 40%–60%.[2] # Function The bacterial CAP or CRP proteins are the closest related non-Popdcproteins. CRP proteins function as cyclic nucleotide-regulated transcription factors that modulate the expression of genes encoding enzymes involved in carbohydrate metabolism. The cyclic AMP-binding domains of these proteins display approximately 25% identity and 60% similarity to the Popeye domain.[3] Significant structural similarity is evident between the Popeye domain and cAMP binding domains of eukaryotic protein kinase A (PKA) and HCN channels.[3] # Ligands The Popeye domain binds cyclic nucleotides and has a binding affinity (IC50) for cAMP of 120 nM, which is comparable to the affinities reported for PKA (100 nM) and HCN4 (240 nM).[3] One of the interacting proteins is the two-pore potassium (K2P) channel TREK-1. In the presence of Popdc proteins, TREK-1 current is increased. This increase was based on an enhanced membrane representation of TREK-1, suggesting a modulation of channel trafficking by Popdc proteins.[3] # Animal studies Genetic inactivation of Popdc2 in mice resulted in bradyarrhythmia, which is strictly stress-dependent. At rest a normal ECG was observed.[3] Gene inactivation in the zebrafish also causes a cardiac arrhythmia phenotype and defective skeletal muscle development.[4]	https://www.wikidoc.org/index.php/POPDC2
9cefca83404601f54e510b51b223b03eab50d9f0	wikidoc	POU3F2	POU3F2 POU domain, class 3, transcription factor 2 is a protein that in humans is encoded by the POU3F2 gene. # Function N-Oct-3 is a protein belonging to a large family of transcription factors that bind to the octameric DNA sequence ATGCAAAT. Most of these proteins share a highly homologous region, referred to as the POU domain, which occurs in several mammalian transcription factors, including the octamer-binding proteins Oct1 (POU2F1; MIM 164175) and Oct2 (POU2F2; MIM 164176), and the pituitary protein Pit1 (PIT1; MIM 173110). Class III POU genes are expressed predominantly in the CNS. It is likely that CNS-specific transcription factors such as these play an important role in mammalian neurogenesis by regulating their diverse patterns of gene expression. # Disease linkage The POU3F2 protein associates with the Bipolar disorder. It is involved in the neocortex development in mice, and is linked to a single nucletide polymorphism, Rs1906252, that is associated with a cognitive phenotype: processing information speed. Chromosome 6q16.1 deletions resulting in loss of one copy of POU3F2 have been shown to cause a human syndrome of susceptibility to obesity and variable levels of developmental delay and Intellectual Disability. # Interactions POU3F2 has been shown to interact with PQBP1.	POU3F2 POU domain, class 3, transcription factor 2 is a protein that in humans is encoded by the POU3F2 gene.[1][2] # Function N-Oct-3 is a protein belonging to a large family of transcription factors that bind to the octameric DNA sequence ATGCAAAT. Most of these proteins share a highly homologous region, referred to as the POU domain, which occurs in several mammalian transcription factors, including the octamer-binding proteins Oct1 (POU2F1; MIM 164175) and Oct2 (POU2F2; MIM 164176), and the pituitary protein Pit1 (PIT1; MIM 173110). Class III POU genes are expressed predominantly in the CNS. It is likely that CNS-specific transcription factors such as these play an important role in mammalian neurogenesis by regulating their diverse patterns of gene expression.[2] # Disease linkage The POU3F2 protein associates with the Bipolar disorder. It is involved in the neocortex development in mice, and is linked to a single nucletide polymorphism, Rs1906252, that is associated with a cognitive phenotype: processing information speed.[3] Chromosome 6q16.1 deletions resulting in loss of one copy of POU3F2 have been shown to cause a human syndrome of susceptibility to obesity and variable levels of developmental delay and Intellectual Disability.[4] # Interactions POU3F2 has been shown to interact with PQBP1.[5]	https://www.wikidoc.org/index.php/POU3F2
14dacdfff715f6e8452ad45b56fab31f0042b587	wikidoc	POU3F4	POU3F4 POU domain, class 3, transcription factor 4 is a protein that in humans is encoded by the POU3F4 gene found on the X chromosome. POU3F4 is involved in the patterning of the neural tube and both the paraventricular and supraoptic nuclei of the hypothalamus in the developing embryo. During development, POU3F4 is also expressed in the mesenchyme of the periotic bone surrounding the inner ear. A “knockout” mice model displayed that alteration to the POU3F4 gene interrupted this mesenchymal cell differentiation in the superior semicircular canal. The deformities observed in mice were similar to those in humans with X-linked non-syndromic deafness (DFN-3). # Clinical significance Genetic testing on various persons has confirmed that mutations of the POU3F4 gene cause X-linked non-syndromic deafness (DFN-3). These known mutations include: - Missense mutation causing the substitution of amino acid glycine for glutamic acid at position 216 - A deletion of the POU3F4 gene and 530 more kilobases upstream - An amino acid substitution of serine for leucine (S228L) in POU3F4 - Frameshift truncation and extension mutations at the POU3F4 C-terminus Physical anomalies caused by POU3F4 mutations that have been recognized by high resolution computed tomography (HRCT) and magnetic resonance imaging (MRI) include absence of the central axis of the cochlea, an abnormally wide lateral internal auditory canal and a thickened stapes footplate. These anomalies are associated with X-linked non-syndromic deafness.	POU3F4 POU domain, class 3, transcription factor 4 is a protein that in humans is encoded by the POU3F4 gene found on the X chromosome.[1][2][3] POU3F4 is involved in the patterning of the neural tube and both the paraventricular and supraoptic nuclei of the hypothalamus in the developing embryo.[4] During development, POU3F4 is also expressed in the mesenchyme of the periotic bone surrounding the inner ear.[5] A “knockout” mice model displayed that alteration to the POU3F4 gene interrupted this mesenchymal cell differentiation in the superior semicircular canal. The deformities observed in mice were similar to those in humans with X-linked non-syndromic deafness (DFN-3).[6] # Clinical significance Genetic testing on various persons has confirmed that mutations of the POU3F4 gene cause X-linked non-syndromic deafness (DFN-3).[7] These known mutations include: - Missense mutation causing the substitution of amino acid glycine for glutamic acid at position 216[8] - A deletion of the POU3F4 gene and 530 more kilobases upstream[9] - An amino acid substitution of serine for leucine (S228L) in POU3F4[9] - Frameshift truncation and extension mutations at the POU3F4 C-terminus[10] Physical anomalies caused by POU3F4 mutations that have been recognized by high resolution computed tomography (HRCT) and magnetic resonance imaging (MRI) include absence of the central axis of the cochlea, an abnormally wide lateral internal auditory canal and a thickened stapes footplate. These anomalies are associated with X-linked non-syndromic deafness.[11]	https://www.wikidoc.org/index.php/POU3F4
64b9cef1bed0c804e754c11fc5c070725531984c	wikidoc	POU4F1	POU4F1 POU domain, class 4, transcription factor 1 (POU4F1) also known as brain-specific homeobox/POU domain protein 3A (BRN3A), homeobox/POU domain protein RDC-1 or Oct-T1 is a protein that in humans is encoded by the POU4F1 gene. BRN3A (POU4F1) is a class IV POU domain-containing transcription factor highly expressed in the developing peripheral sensory nervous system (dorsal root ganglia, trigeminal ganglion, and hindbrain sensory ganglia), certain regions of the central nervous system, retinal neurons called ganglion cells, and in cells of the B- and T-lymphocytic lineages. # Discovery Brn3a was initially discovered in mice based on homology to the prototypal POU transcription factors Pit1 (Pituitary-specific positive transcription factor 1, Pou1f1), Oct1 (Pou2f1), and the Caenorhabditis elegans factor Unc86, and named Brn3. When multiple members of the Brn3 gene class were discovered, it was renamed Brn3.0 and Brn3a by different groups of researchers. Subsequently, the gene was systematically renamed Pou4f1 in mice and POU4F1 in humans. The protein product is still frequently referred to as Brn3a. # Function In addition to sensory neurons, in rodents and birds (and presumably humans) Brn3a is expressed in multiple sites in the central nervous system, including the spinal cord, midbrain superior colliculus, red nucleus, nucleus ambiguus, inferior olivary nucleus, habenula, and retina. Mice with null mutations ("knockouts") in Brn3a die at birth, due to developmental defects in the nucleus ambiguus, which is essential for respiration. Brn3a is a transcription factor which acts in development by regulating downstream "target" genes. Microarrays have been used to determine many genes downstream of Brn3a in peripheral sensory neurons. In the sensory neurons Brn3a is co-expressed with the LIM domain transcription factor ISL1 or Islet1, and has many downstream targets in common with Isl1. Pou4f1/Isl1 double mutant mice show strong epistatic effects in regulation of many downstream genes in the sensory neurons of double mutant mouse embryos. Although the homozygous Brn3a null mutation is lethal at birth in mice, Brn3a null heterozygotes have no known phenotype. i.e. the Brn3a null mutation is completely recessive. This can be explained by gene dosage compensation due to autoregulation, in which expression of the remaining copy of the Pou4f1 gene is increased in heterozygotes, leading to near-normal expression of its downstream targets. The combination of homozygote lethality and dosage compensation in heterozygotes may explain why POU4F1 mutations have not been identified in any human disease, whereas diseases are associated with several other members of the POU domain transcription factor class. # Interactions POU4F1 has been shown to interact with Estrogen receptor alpha, RIT2 and Ewing sarcoma breakpoint region 1.	POU4F1 POU domain, class 4, transcription factor 1 (POU4F1) also known as brain-specific homeobox/POU domain protein 3A (BRN3A), homeobox/POU domain protein RDC-1 or Oct-T1 is a protein that in humans is encoded by the POU4F1 gene.[1][2] BRN3A (POU4F1) is a class IV POU domain-containing transcription factor highly expressed in the developing peripheral sensory nervous system (dorsal root ganglia, trigeminal ganglion, and hindbrain sensory ganglia), certain regions of the central nervous system, retinal neurons called ganglion cells, and in cells of the B- and T-lymphocytic lineages.[2][3] # Discovery Brn3a was initially discovered in mice based on homology to the prototypal POU transcription factors Pit1 (Pituitary-specific positive transcription factor 1, Pou1f1), Oct1 (Pou2f1), and the Caenorhabditis elegans factor Unc86, and named Brn3.[4] When multiple members of the Brn3 gene class were discovered, it was renamed Brn3.0 and Brn3a by different groups of researchers.[3][5] Subsequently, the gene was systematically renamed Pou4f1 in mice and POU4F1 in humans. The protein product is still frequently referred to as Brn3a. # Function In addition to sensory neurons, in rodents and birds (and presumably humans) Brn3a is expressed in multiple sites in the central nervous system, including the spinal cord, midbrain superior colliculus, red nucleus, nucleus ambiguus, inferior olivary nucleus, habenula, and retina.[6] Mice with null mutations ("knockouts") in Brn3a die at birth, due to developmental defects in the nucleus ambiguus, which is essential for respiration.[7][8][9] Brn3a is a transcription factor which acts in development by regulating downstream "target" genes. Microarrays have been used to determine many genes downstream of Brn3a in peripheral sensory neurons.[10][11] In the sensory neurons Brn3a is co-expressed with the LIM domain transcription factor ISL1 or Islet1, and has many downstream targets in common with Isl1.[12] Pou4f1/Isl1 double mutant mice show strong epistatic effects in regulation of many downstream genes in the sensory neurons of double mutant mouse embryos.[13] Although the homozygous Brn3a null mutation is lethal at birth in mice, Brn3a null heterozygotes have no known phenotype. i.e. the Brn3a null mutation is completely recessive. This can be explained by gene dosage compensation due to autoregulation,[14] in which expression of the remaining copy of the Pou4f1 gene is increased in heterozygotes, leading to near-normal expression of its downstream targets.[10] The combination of homozygote lethality and dosage compensation in heterozygotes may explain why POU4F1 mutations have not been identified in any human disease, whereas diseases are associated with several other members of the POU domain transcription factor class. # Interactions POU4F1 has been shown to interact with Estrogen receptor alpha,[15] RIT2[16] and Ewing sarcoma breakpoint region 1.[17]	https://www.wikidoc.org/index.php/POU4F1
6cd049da77d03fb9fee484938b4d6f65a9debf91	wikidoc	PPAP2B	PPAP2B Lipid phosphate phosphohydrolase 3 (LPP3), also known as phospholipid phosphatase 3 (PLPP3) and phosphatidic acid phosphatase type 2B (PAP-2b or PPAP2B), is an enzyme that in humans is encoded by the PPAP2B gene on chromosome 1. It is ubiquitously expressed in many tissues and cell types. LPP3 is a cell-surface glycoprotein that hydrolyzes extracellular lysophosphatidic acid (LPA) and short-chain phosphatidic acid. Its function allows it to regulate vascular and embryonic development by inhibiting LPA signaling, which is associated with a wide range of human diseases, including cardiovascular disease and cancer, as well as developmental defects. The PPAP2B gene also contains one of 27 loci associated with increased risk of coronary artery disease. # Structure ## Gene The PPAP2B gene resides on chromosome 1 at the band 1p32.2 and includes 6 exons. ## Protein LPP3 is a member of the PAP-related phosphoesterase family. It is a type 2 activity PAP, which localizes to the plasma membrane, and is one of four known LPP isoforms. As an integral membrane protein, LPP3 contains six hydrophobic transmembrane domains and a hydrophilic catalytic site composed of three conserved domains. One catalytic domain is proposed to bind the substrate while the other two contribute to dephosphorylation of the substrate. The catalytic site typically faces the extracellular matrix when located on the cell membrane and faces the lumen when located in intracellular membranes. This protein can form homo- and hetero-oligomers. # Function This protein is a membrane glycoprotein localized at the cell plasma membrane. It has been shown to actively hydrolyze extracellular lysophosphatidic acid (LPA) and short-chain phosphatidic acid. As an LPA inhibitor, PPAP2B is known to suppress LPA receptor mediated cellular signaling, which is associated with activation of vascular and blood cells and epithelial cell migration and proliferation. In response to dynamic atherorelevant-flows, PPAP2B can promote anti-inflammatory phenotype via inhibition of LPA signaling and maintain vascular integrity of endothelial monolayer. This flow-sensitive PPAP2B expression is inhibited by microRNA-92a and activated by transcription factor KLF2. In addition to LPA receptor-mediated signaling, PPAP2B is also associated with Wnt signaling, functioning in embryonic development for proper formation of important tissues including bone, heart and muscle. The phenotype of axis duplication in mice globally lacking PPAP2B resembles that observed in animals with altered Wnt signaling. Furthermore, Wnt signaling mediated TCF/LEF-transcription via β-catenin is upregulated in PPAP2B null embryonic stem cells, implicating LPP3 as a negative regulator of the Wnt pathway. # Clinical Significance Due to the regulatory role of LPP3 in vascular and embryonic development, inactivation of this protein can contribute to cardiovascular disease and developmental complications. For example, inducible inactivation of LPP3 in both endothelial and hematopoietic cells leads to atherosclerosis due to accumulation of LPA in human plaques. Likewise, plasma LPA levels are significantly elevated in patients with acute coronary syndromes. It was further observed that reduced levels of endothelial LPP3 is associated with disturbed flow and mechano-regulation in blood vessels. During embryonic development in mice, inactivation of LPP3 results in early lethality in part due to failure of extra-embryonic vascular development. Abnormal activation of LPA signaling has also been implicated in cancer, fibrotic disorders, and metabolic syndrome (involving insulin resistance). ## Clinical Marker In humans, PPAP2B emerged as 1 of 13 new loci associated with coronary artery disease by genome-wide association studies (GWAS). This prediction appears to be independent of traditional risk factors for cardiovascular disease such as high cholesterol levels, high blood pressure, obesity, smoking, and diabetes mellitus. Additionally, a multi-locus genetic risk score study, based on a combination of 27 loci including the PPAP2B gene, identified individuals at increased risk for both incident and recurrent coronary artery disease events, as well as an enhanced clinical benefit from statin therapy. The study was based on a community cohort study (the Malmo Diet and Cancer study) and four additional randomized controlled trials of primary prevention cohorts (JUPITER and ASCOT) and secondary prevention cohorts (CARE and PROVE IT-TIMI 22). Taken together, these findings also suggest that PPAP2B and LPA may serve a role in predicting and screening coronary artery disease for early prevention. # Interactions ## Interactive Pathway Map LPP3 participates in interactions within the triacylglyceride synthesis and sphingolipid metabolism pathways.	PPAP2B Lipid phosphate phosphohydrolase 3 (LPP3), also known as phospholipid phosphatase 3 (PLPP3) and phosphatidic acid phosphatase type 2B (PAP-2b or PPAP2B), is an enzyme that in humans is encoded by the PPAP2B gene on chromosome 1.[1][2][3] It is ubiquitously expressed in many tissues and cell types.[4] LPP3 is a cell-surface glycoprotein that hydrolyzes extracellular lysophosphatidic acid (LPA) and short-chain phosphatidic acid.[5] Its function allows it to regulate vascular and embryonic development by inhibiting LPA signaling, which is associated with a wide range of human diseases, including cardiovascular disease and cancer, as well as developmental defects.[6] The PPAP2B gene also contains one of 27 loci associated with increased risk of coronary artery disease.[7] # Structure ## Gene The PPAP2B gene resides on chromosome 1 at the band 1p32.2 and includes 6 exons.[2] ## Protein LPP3 is a member of the PAP-related phosphoesterase family.[3] It is a type 2 activity PAP, which localizes to the plasma membrane, and is one of four known LPP isoforms. As an integral membrane protein, LPP3 contains six hydrophobic transmembrane domains and a hydrophilic catalytic site composed of three conserved domains.[8][9] One catalytic domain is proposed to bind the substrate while the other two contribute to dephosphorylation of the substrate. The catalytic site typically faces the extracellular matrix when located on the cell membrane and faces the lumen when located in intracellular membranes. This protein can form homo- and hetero-oligomers.[9] # Function This protein is a membrane glycoprotein localized at the cell plasma membrane. It has been shown to actively hydrolyze extracellular lysophosphatidic acid (LPA) and short-chain phosphatidic acid. [5] As an LPA inhibitor, PPAP2B is known to suppress LPA receptor mediated cellular signaling, which is associated with activation of vascular and blood cells and epithelial cell migration and proliferation.[10][11] In response to dynamic atherorelevant-flows, PPAP2B can promote anti-inflammatory phenotype via inhibition of LPA signaling and maintain vascular integrity of endothelial monolayer. This flow-sensitive PPAP2B expression is inhibited by microRNA-92a and activated by transcription factor KLF2.[12] In addition to LPA receptor-mediated signaling, PPAP2B is also associated with Wnt signaling, functioning in embryonic development for proper formation of important tissues including bone, heart and muscle. The phenotype of axis duplication in mice globally lacking PPAP2B resembles that observed in animals with altered Wnt signaling.[13] Furthermore, Wnt signaling mediated TCF/LEF-transcription via β-catenin is upregulated in PPAP2B null embryonic stem cells, implicating LPP3 as a negative regulator of the Wnt pathway.[14] # Clinical Significance Due to the regulatory role of LPP3 in vascular and embryonic development, inactivation of this protein can contribute to cardiovascular disease and developmental complications. For example, inducible inactivation of LPP3 in both endothelial and hematopoietic cells leads to atherosclerosis due to accumulation of LPA in human plaques.[6][15] Likewise, plasma LPA levels are significantly elevated in patients with acute coronary syndromes.[16] It was further observed that reduced levels of endothelial LPP3 is associated with disturbed flow and mechano-regulation in blood vessels.[12] During embryonic development in mice, inactivation of LPP3 results in early lethality in part due to failure of extra-embryonic vascular development.[17] Abnormal activation of LPA signaling has also been implicated in cancer, fibrotic disorders, and metabolic syndrome (involving insulin resistance).[18][19] ## Clinical Marker In humans, PPAP2B emerged as 1 of 13 new loci associated with coronary artery disease by genome-wide association studies (GWAS).[20][21] This prediction appears to be independent of traditional risk factors for cardiovascular disease such as high cholesterol levels, high blood pressure, obesity, smoking, and diabetes mellitus. Additionally, a multi-locus genetic risk score study, based on a combination of 27 loci including the PPAP2B gene, identified individuals at increased risk for both incident and recurrent coronary artery disease events, as well as an enhanced clinical benefit from statin therapy. The study was based on a community cohort study (the Malmo Diet and Cancer study) and four additional randomized controlled trials of primary prevention cohorts (JUPITER and ASCOT) and secondary prevention cohorts (CARE and PROVE IT-TIMI 22).[7] Taken together, these findings also suggest that PPAP2B and LPA may serve a role in predicting and screening coronary artery disease for early prevention.[10] # Interactions ## Interactive Pathway Map LPP3 participates in interactions within the triacylglyceride synthesis and sphingolipid metabolism pathways.	https://www.wikidoc.org/index.php/PPAP2B
5db913f5dff6ac0b3626f27509c64b755bd3c57c	wikidoc	PPP1CA	PPP1CA Serine/threonine-protein phosphatase PP1-alpha catalytic subunit is an enzyme that in humans is encoded by the PPP1CA gene. # Function The protein encoded by this gene is one of the three catalytic subunits of protein phosphatase 1 (PP1). PP1 is a serine/threonine specific protein phosphatase known to be involved in the regulation of a variety of cellular processes, such as cell division, glycogen metabolism, muscle contractility, protein synthesis, and HIV-1 viral transcription. Increased PP1 activity has been observed in the end stage of heart failure. Studies in both human and mice suggest that PP1 is an important regulator of cardiac function. Mouse studies also suggest that PP1 functions as a suppressor of learning and memory. Three alternatively spliced transcript variants encoding different isoforms have been found for this gene. # Interactive pathway map Click on genes, proteins and metabolites below to link to respective articles. - ↑ The interactive pathway map can be edited at WikiPathways: "NicotineDopaminergic_WP1602"..mw-parser-output cite.citation{font-style:inherit}.mw-parser-output q{quotes:"\"""\"""'""'"}.mw-parser-output code.cs1-code{color:inherit;background:inherit;border:inherit;padding:inherit}.mw-parser-output .cs1-lock-free a{background:url("")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-limited a,.mw-parser-output .cs1-lock-registration a{background:url("")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-subscription a{background:url("")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration{color:#555}.mw-parser-output .cs1-subscription span,.mw-parser-output .cs1-registration span{border-bottom:1px dotted;cursor:help}.mw-parser-output .cs1-hidden-error{display:none;font-size:100%}.mw-parser-output .cs1-visible-error{display:none;font-size:100%}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration,.mw-parser-output .cs1-format{font-size:95%}.mw-parser-output .cs1-kern-left,.mw-parser-output .cs1-kern-wl-left{padding-left:0.2em}.mw-parser-output .cs1-kern-right,.mw-parser-output .cs1-kern-wl-right{padding-right:0.2em} # Interactions PPP1CA has been shown to interact with: - AKAP11, - BCL2-like 1, - BCL2L2, - BRCA1, - CDC5L, - Host cell factor C1, - KvLQT1, - LMTK2, - PHACTR3, - PPP1R15A, - PPP1R8, - PPP1R9B, - Protein kinase R, and - SMARCB1.	PPP1CA Serine/threonine-protein phosphatase PP1-alpha catalytic subunit is an enzyme that in humans is encoded by the PPP1CA gene. # Function The protein encoded by this gene is one of the three catalytic subunits of protein phosphatase 1 (PP1). PP1 is a serine/threonine specific protein phosphatase known to be involved in the regulation of a variety of cellular processes, such as cell division, glycogen metabolism, muscle contractility, protein synthesis, and HIV-1 viral transcription. Increased PP1 activity has been observed in the end stage of heart failure. Studies in both human and mice suggest that PP1 is an important regulator of cardiac function. Mouse studies also suggest that PP1 functions as a suppressor of learning and memory. Three alternatively spliced transcript variants encoding different isoforms have been found for this gene.[1] # Interactive pathway map Click on genes, proteins and metabolites below to link to respective articles.[§ 1] - ↑ The interactive pathway map can be edited at WikiPathways: "NicotineDopaminergic_WP1602"..mw-parser-output cite.citation{font-style:inherit}.mw-parser-output q{quotes:"\"""\"""'""'"}.mw-parser-output code.cs1-code{color:inherit;background:inherit;border:inherit;padding:inherit}.mw-parser-output .cs1-lock-free a{background:url("https://upload.wikimedia.org/wikipedia/commons/thumb/6/65/Lock-green.svg/9px-Lock-green.svg.png")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-limited a,.mw-parser-output .cs1-lock-registration a{background:url("https://upload.wikimedia.org/wikipedia/commons/thumb/d/d6/Lock-gray-alt-2.svg/9px-Lock-gray-alt-2.svg.png")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-subscription a{background:url("https://upload.wikimedia.org/wikipedia/commons/thumb/a/aa/Lock-red-alt-2.svg/9px-Lock-red-alt-2.svg.png")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration{color:#555}.mw-parser-output .cs1-subscription span,.mw-parser-output .cs1-registration span{border-bottom:1px dotted;cursor:help}.mw-parser-output .cs1-hidden-error{display:none;font-size:100%}.mw-parser-output .cs1-visible-error{display:none;font-size:100%}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration,.mw-parser-output .cs1-format{font-size:95%}.mw-parser-output .cs1-kern-left,.mw-parser-output .cs1-kern-wl-left{padding-left:0.2em}.mw-parser-output .cs1-kern-right,.mw-parser-output .cs1-kern-wl-right{padding-right:0.2em} # Interactions PPP1CA has been shown to interact with: - AKAP11,[2][3] - BCL2-like 1,[4] - BCL2L2,[4] - BRCA1,[5] - CDC5L,[6] - Host cell factor C1,[7] - KvLQT1,[8] - LMTK2,[9] - PHACTR3,[10] - PPP1R15A,[11][12][13] - PPP1R8,[7][14] - PPP1R9B,[15] - Protein kinase R,[16] and - SMARCB1.[12]	https://www.wikidoc.org/index.php/PPP1CA
dfc892c98528e74dd4e0a4742f993c950e7d507d	wikidoc	PPP1CB	PPP1CB Serine/threonine-protein phosphatase PP1-beta catalytic subunit is an enzyme that in humans is encoded by the PPP1CB gene. The protein encoded by this gene is one of the three catalytic subunits of protein phosphatase 1 (PP1). PP1 is a serine/threonine specific protein phosphatase known to be involved in the regulation of a variety of cellular processes, such as cell division, glycogen metabolism, muscle contractility, protein synthesis, and HIV-1 viral transcription. Mouse studies suggest that PP1 functions as a suppressor of learning and memory. Two alternatively spliced transcript variants encoding distinct isoforms have been observed. # Interactions PPP1CB has been shown to interact with PPP1R15A, Nucleolin, SMARCB1 and PPP1R9B.	PPP1CB Serine/threonine-protein phosphatase PP1-beta catalytic subunit is an enzyme that in humans is encoded by the PPP1CB gene.[1] The protein encoded by this gene is one of the three catalytic subunits of protein phosphatase 1 (PP1). PP1 is a serine/threonine specific protein phosphatase known to be involved in the regulation of a variety of cellular processes, such as cell division, glycogen metabolism, muscle contractility, protein synthesis, and HIV-1 viral transcription. Mouse studies suggest that PP1 functions as a suppressor of learning and memory. Two alternatively spliced transcript variants encoding distinct isoforms have been observed.[2] # Interactions PPP1CB has been shown to interact with PPP1R15A,[3][4] Nucleolin,[5] SMARCB1[3] and PPP1R9B.[6]	https://www.wikidoc.org/index.php/PPP1CB
a39ca121a66d748683eaa5c2e12ade746ab32e96	wikidoc	PPP1R8	PPP1R8 Nuclear inhibitor of protein phosphatase 1 is an enzyme that in humans is encoded by the PPP1R8 gene. This gene, through alternative splicing, encodes three different isoforms. Two of the protein isoforms encoded by this gene are specific inhibitors of type 1 serine/threonine protein phosphatases and can bind but not cleave RNA. The third protein isoform lacks the phosphatase inhibitory function but is a single-strand endoribonuclease comparable to RNase E of E. coli. This isoform requires magnesium for its function and cleaves specific sites in A+U-rich regions of RNA. # Interactions PPP1R8 has been shown to interact with PPP1CA, Histone deacetylase 2, SF3B1 EED and the EZH2 domain of PRC2.	PPP1R8 Nuclear inhibitor of protein phosphatase 1 is an enzyme that in humans is encoded by the PPP1R8 gene.[1][2][3] This gene, through alternative splicing, encodes three different isoforms. Two of the protein isoforms encoded by this gene are specific inhibitors of type 1 serine/threonine protein phosphatases and can bind but not cleave RNA. The third protein isoform lacks the phosphatase inhibitory function but is a single-strand endoribonuclease comparable to RNase E of E. coli. This isoform requires magnesium for its function and cleaves specific sites in A+U-rich regions of RNA.[3] # Interactions PPP1R8 has been shown to interact with PPP1CA,[4][5] Histone deacetylase 2,[4] SF3B1[6] EED [4] and the EZH2 domain of PRC2.[7]	https://www.wikidoc.org/index.php/PPP1R8
306e4c135f0c29de924d6b7bbec1a3ebe7fb4bf5	wikidoc	PPP2CB	PPP2CB Serine/threonine-protein phosphatase 2A catalytic subunit beta isoform is an enzyme that in humans is encoded by the PPP2CB gene. # Function This gene encodes the phosphatase 2A catalytic subunit. Protein phosphatase 2A is one of the four major Ser/Thr phosphatases, and it is implicated in the negative control of cell growth and division. It consists of a common heteromeric core enzyme, which is composed of a catalytic subunit and a constant regulatory subunit, that associates with a variety of regulatory subunits. This gene encodes a beta isoform of the catalytic subunit. Two transcript variants encoding the same protein have been identified for this gene. # Interactions PPP2CB has been shown to interact with TLX1, PPP2R1B and PPP2R1A.	PPP2CB Serine/threonine-protein phosphatase 2A catalytic subunit beta isoform is an enzyme that in humans is encoded by the PPP2CB gene.[1] # Function This gene encodes the phosphatase 2A catalytic subunit. Protein phosphatase 2A is one of the four major Ser/Thr phosphatases, and it is implicated in the negative control of cell growth and division. It consists of a common heteromeric core enzyme, which is composed of a catalytic subunit and a constant regulatory subunit, that associates with a variety of regulatory subunits. This gene encodes a beta isoform of the catalytic subunit. Two transcript variants encoding the same protein have been identified for this gene.[2] # Interactions PPP2CB has been shown to interact with TLX1,[3] PPP2R1B[4] and PPP2R1A.[4][5]	https://www.wikidoc.org/index.php/PPP2CB
0a14ca93278789096f528b7062f1b20de67f9789	wikidoc	PPP2R4	PPP2R4 Serine/threonine-protein phosphatase 2A regulatory subunit B' is an enzyme that in humans is encoded by the PPP2R4 gene. Protein phosphatase 2A is one of the four major Ser/Thr phosphatases and is implicated in the negative control of cell growth and division. Protein phosphatase 2A holoenzymes are heterotrimeric proteins composed of a structural subunit A, a catalytic subunit C, and a regulatory subunit B. The regulatory subunit is encoded by a diverse set of genes that have been grouped into the B/PR55, B'/PR61, and B/PR72 families. These different regulatory subunits confer distinct enzymatic specificities and intracellular localizations to the holozenzyme. The product of this gene belongs to the B' family. This gene encodes a specific phosphotyrosyl phosphatase activator of the dimeric form of protein phosphatase 2A. Alternative splicing results in multiple transcript variants encoding different isoforms. # Interactions PPP2R4 has been shown to interact with PPP2R3A, CCNG1 and Janus kinase 2.	PPP2R4 Serine/threonine-protein phosphatase 2A regulatory subunit B' is an enzyme that in humans is encoded by the PPP2R4 gene.[1][2] Protein phosphatase 2A is one of the four major Ser/Thr phosphatases and is implicated in the negative control of cell growth and division. Protein phosphatase 2A holoenzymes are heterotrimeric proteins composed of a structural subunit A, a catalytic subunit C, and a regulatory subunit B. The regulatory subunit is encoded by a diverse set of genes that have been grouped into the B/PR55, B'/PR61, and B/PR72 families. These different regulatory subunits confer distinct enzymatic specificities and intracellular localizations to the holozenzyme. The product of this gene belongs to the B' family. This gene encodes a specific phosphotyrosyl phosphatase activator of the dimeric form of protein phosphatase 2A. Alternative splicing results in multiple transcript variants encoding different isoforms.[2] # Interactions PPP2R4 has been shown to interact with PPP2R3A,[3] CCNG1[4] and Janus kinase 2.[5]	https://www.wikidoc.org/index.php/PPP2R4
cb04fbffb499550ef445e99c9482260dea4b1928	wikidoc	PRDM12	PRDM12 PR domain zinc finger protein 12 is a protein that in humans is encoded by the PRDM12 gene. This gene is normally switched on during the development of pain-sensing nerve cells. People with homozygous mutations of the PRDM12 gene experience congenital insensitivity to pain (CIP). PRMD12 is a part of a larger domain that mediate histone methyltransferases. Enzymes target gene promoters in order to control gene expression. # Structure The human protein isoform is made up of 367 amino acids containing a PR domain (related to the SET methyltransferase domain), 3 zinc fingers, and a C-terminal polyalanine tract. # Function PRDM12 influences the development of nerve cells that assist in perception and sensation of pain, which is an important evolutionary advantage. In humans, mutations in the PRDM12 gene can cause loss of pain perception brought on by defects in the development of sensory neurons. It also has a range of interactions with and affects on various proteins. In vertebrates, PRDM12 directly represses the DBX1 and NKX6 genes. This is thought to be accomplished by utilizing G9a, a strong H3K9 methyltransferase. The indicated result of PRDM12's cross-repressive interaction with the DBX1 and NKX6 genes is that the PRDM12 partially acts as a promoter of V1 interneurons (which are essential to the locomotion of vertebrates). It is a member of thegroup of PR- domain-containing zinc-finger familyfingers, "which appear to function as negative regulators of oncogenesis and include the tumor-associated genes MDS1-EVI1, RIZ, BLIMP1, MEL1 and PFM1. PRDM12 therefore represents an attractive candidate tumour suppressor gene within the der(9) CDR ." Several members of the PRDM family are found to be acting as a tumor suppressor or a factor driving oncogenic processes in human diseases, specifically and most notably in solid cancers and hematological malignancies. It is hoped that further study may reveal target genes of PRDM proteins so a greater understanding of the functions of the PRDM family can be achieved. In Xenopus embryos, PRDM12 expression "was partially co-localized with the lateral expression regions" of the SIX1, PAX3, ISLET1, and PAX6 genes, but not those of the FOXD3 and SIX3 genes. In cases where BMP4 was overexpressed, embryos showed an increase in PRDM12 expression. Data indicated that the regulation of PRDM12 expression in Xenopus embryos was controlled by BMP and Wnt signaling. PRDM12 codes for a protein which regulates the neurological path through which pain in perceived, known as PR domain zinc finger protein 12. The protein plays a vital role in the regulation of histone H3-K9 dimethylation. PRDM12’s protein also directly affects the development of nerve-endings. The protein is synthesized at the same developmental point as the neurons which sense pain and the growth of the two is linked. The mutation of this gene results in a non-functioning protein, which in-turn causes a failure to develop the pain-sensing nerve endings and an organism without sensitivity to pain. This lack of pain-sensing nerve endings can cause severe harm to the individual, as they cannot sense when they are injured by something such as a hot stove-eye or broken bone. PRDM12’s protein has also been found to be a tumor suppressor for chronic myloid leukemia. The protein controls gene expression by modifying chromatin. PRDMs as a family tend to require enzyme help to modify histones, with some exceptions. # Clinical significance In humans, mutations in the PRDM12 gene can cause loss of pain perception brought on by defects in the development of sensory neurons.There are a number of diseases and conditions that can result from mutations in the PRDM12 gene. Congenital insensitivity to pain (CIP) is a characterized by an inability to feel pain. This is a rare condition that is present at birth due to a lack of, or malfunction of, nociceptors. There are three different genes that can be mutated to cause CIP. First, a mutation in the SCN9A makes it impossible for nocicepters to respond to harmful stimuli because it causes the gene to lose its function. Second, a mutation in the NTRK1 causes a loss of function for the gene and leads to a failure in nociceptor development. Finally, researchers have identified 10 homozygous mutations on PRDM12 that appeared to be linked to this condition. Past research has shown that PRDM12 is involved in the modification of chromatin. Chromatin can turn genes off and on by attaching itself to chromosomes and acting as an epigenetic switch. Chromatin play a huge role in neuron development, so researcher hypothesized that that mutations in the PRDM12 gene prevent nociceptors and nerve fibers from developing normally. They then studied the nerve biopsies of patients with this condition and found that the patients affected by this condition are lacking pain sensing never fibers in their legs, or only have half the amount they should have. Another condition caused by mutations in the PRDM12 gene is hereditary sensory and autonomic neuropathy type VIII.HSAN VIII is a very rare autosomal recessive inherited disorder that also begins at birth and is characterized by an inability to feel pain and an inability to sweat (anhidrosis). Anhidrosis can cause frequent episodes of high body temperature of high fever. Other signs of this condition can include early loss of teeth, server soft tissue injuries, dental caries and submucosal abscesses, hypomineralization of primary, and mandibular osteomyelitis. Abnormal functioning of the sensory nerves is what causes the sensory loss in patients with this condition. A third condition that may be caused by a mutation in the PRDM12 gene is Midface toddler excoriation syndrome (MiTES). MiTES is an newly discovered condition that has recently been reported in three children who were unrelated. Persistent scratching around the nose and eyes from the first year of life results in deep, scarring wounds in the patients with this condition. Doctors say because of these wounds, it is easy to mistake this condition with child abuse. Researchers found that four out of the five patients with MiTES have the same autosomal recessive mutations in the PRDM12 gene that causes HSAN VIII. Members of the PRDM family have all been connected to over-expression, epigentic splicing, deletion, or mutations in various types of cancer. PRDM12 in particular has been found to play a role in Chronic myeloid leukaemia, which is a clonal stem cell disorder. Researchers mapped the microdeletions and identified a minimal common deleted region. Within this common deleted region was the PRDM12 gene. Because the PRDM family appears to includes tumor suppressor genes and functions as negative regulators of oncogenesis, PDRM12 represents an ideal candidate tumor suppressor gene for chronic myeloid leukaemia.	PRDM12 PR domain zinc finger protein 12 is a protein that in humans is encoded by the PRDM12 gene. This gene is normally switched on during the development of pain-sensing nerve cells. People with homozygous mutations of the PRDM12 gene experience congenital insensitivity to pain (CIP).[1][2] PRMD12 is a part of a larger domain that mediate histone methyltransferases. Enzymes target gene promoters in order to control gene expression.[3] # Structure The human protein isoform is made up of 367 amino acids containing a PR domain (related to the SET methyltransferase domain), 3 zinc fingers, and a C-terminal polyalanine tract.[1] # Function PRDM12 influences the development of nerve cells that assist in perception and sensation of pain, which is an important evolutionary advantage. In humans, mutations in the PRDM12 gene can cause loss of pain perception brought on by defects in the development of sensory neurons.[4] It also has a range of interactions with and affects on various proteins. In vertebrates, PRDM12 directly represses the DBX1 and NKX6 genes. This is thought to be accomplished by utilizing G9a, a strong H3K9 methyltransferase. The indicated result of PRDM12's cross-repressive interaction with the DBX1 and NKX6 genes is that the PRDM12 partially acts as a promoter of V1 interneurons (which are essential to the locomotion of vertebrates).[5] It is a member of thegroup of PR- domain-containing zinc-finger familyfingers, "which appear to function as negative regulators of oncogenesis and include the tumor-associated genes MDS1-EVI1, RIZ, BLIMP1, MEL1 and PFM1. PRDM12 therefore represents an attractive candidate tumour suppressor gene within the der(9) [derivative chromosome 9] CDR [commonly deleted region]."[6] Several members of the PRDM family are found to be acting as a tumor suppressor or a factor driving oncogenic processes in human diseases, specifically and most notably in solid cancers and hematological malignancies. It is hoped that further study may reveal target genes of PRDM proteins so a greater understanding of the functions of the PRDM family can be achieved.[7] In Xenopus embryos, PRDM12 expression "was partially co-localized with the lateral expression regions" of the SIX1, PAX3, ISLET1, and PAX6 genes, but not those of the FOXD3 and SIX3 genes. In cases where BMP4 was overexpressed, embryos showed an increase in PRDM12 expression. Data indicated that the regulation of PRDM12 expression in Xenopus embryos was controlled by BMP and Wnt signaling.[8] PRDM12 codes for a protein which regulates the neurological path through which pain in perceived, known as PR domain zinc finger protein 12.[9] The protein plays a vital role in the regulation of histone H3-K9 dimethylation.[10][11] PRDM12’s protein also directly affects the development of nerve-endings. The protein is synthesized at the same developmental point as the neurons which sense pain and the growth of the two is linked.[2] The mutation of this gene results in a non-functioning protein, which in-turn causes a failure to develop the pain-sensing nerve endings and an organism without sensitivity to pain.[12] This lack of pain-sensing nerve endings can cause severe harm to the individual, as they cannot sense when they are injured by something such as a hot stove-eye or broken bone.[2] PRDM12’s protein has also been found to be a tumor suppressor for chronic myloid leukemia.[13] The protein controls gene expression by modifying chromatin.[12] PRDMs as a family tend to require enzyme help to modify histones, with some exceptions.[14] # Clinical significance In humans, mutations in the PRDM12 gene can cause loss of pain perception brought on by defects in the development of sensory neurons.[15]There are a number of diseases and conditions that can result from mutations in the PRDM12 gene. Congenital insensitivity to pain (CIP) is a characterized by an inability to feel pain.[16] This is a rare condition that is present at birth due to a lack of, or malfunction of, nociceptors.[16] There are three different genes that can be mutated to cause CIP. First, a mutation in the SCN9A makes it impossible for nocicepters to respond to harmful stimuli because it causes the gene to lose its function.[16] Second, a mutation in the NTRK1 causes a loss of function for the gene and leads to a failure in nociceptor development.[16] Finally, researchers have identified 10 homozygous mutations on PRDM12 that appeared to be linked to this condition.[12] Past research has shown that PRDM12 is involved in the modification of chromatin.[12] Chromatin can turn genes off and on by attaching itself to chromosomes and acting as an epigenetic switch.[12] Chromatin play a huge role in neuron development, so researcher hypothesized that that mutations in the PRDM12 gene prevent nociceptors and nerve fibers from developing normally. [12] They then studied the nerve biopsies of patients with this condition and found that the patients affected by this condition are lacking pain sensing never fibers in their legs, or only have half the amount they should have.[12] Another condition caused by mutations in the PRDM12 gene is hereditary sensory and autonomic neuropathy type VIII.[17]HSAN VIII is a very rare autosomal recessive inherited disorder that also begins at birth and is characterized by an inability to feel pain and an inability to sweat (anhidrosis).[17] Anhidrosis can cause frequent episodes of high body temperature of high fever.[17] Other signs of this condition can include early loss of teeth, server soft tissue injuries, dental caries and submucosal abscesses, hypomineralization of primary, and mandibular osteomyelitis.[18] Abnormal functioning of the sensory nerves is what causes the sensory loss in patients with this condition.[17] A third condition that may be caused by a mutation in the PRDM12 gene is Midface toddler excoriation syndrome (MiTES).[19] MiTES is an newly discovered condition that has recently been reported in three children who were unrelated.[19] Persistent scratching around the nose and eyes from the first year of life results in deep, scarring wounds in the patients with this condition.[19] Doctors say because of these wounds, it is easy to mistake this condition with child abuse.[19] Researchers found that four out of the five patients with MiTES have the same autosomal recessive mutations in the PRDM12 gene that causes HSAN VIII.[19] Members of the PRDM family have all been connected to over-expression, epigentic splicing, deletion, or mutations in various types of cancer.[20] PRDM12 in particular has been found to play a role in Chronic myeloid leukaemia, which is a clonal stem cell disorder.[21] Researchers mapped the microdeletions and identified a minimal common deleted region.[21] Within this common deleted region was the PRDM12 gene.[21] Because the PRDM family appears to includes tumor suppressor genes and functions as negative regulators of oncogenesis, PDRM12 represents an ideal candidate tumor suppressor gene for chronic myeloid leukaemia.[21]	https://www.wikidoc.org/index.php/PRDM12
832665799b0c803b67bc3184b49da95d53e39e77	wikidoc	PRDM16	PRDM16 PR domain containing 16, also known as PRDM16, is a protein which in humans is encoded by the PRDM16 gene. PRDM16 acts as a transcription coregulator that controls the development of brown adipocytes in brown adipose tissue. Previously, this coregulator was believed to be present only in brown adipose tissue, but more recent studies have shown that PRDM16 is highly expressed in subcutaneous white adipose tissue as well. # Function The protein encoded by this gene is a zinc finger transcription factor. PRDM16 controls the cell fate between muscle and brown fat cells. Loss of PRDM16 from brown fat precursors causes a loss of brown fat characteristics and promotes muscle differentiation. # Clinical significance The reciprocal translocation t(1;3)(p36;q21) occurs in a subset of myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). This gene is located near the 1p36.3 breakpoint and has been shown to be specifically expressed in the t(1:3)(p36,q21)-positive MDS/AML. The protein encoded by this gene contains an N-terminal PR domain. The translocation results in the overexpression of a truncated version of this protein that lacks the PR domain, which may play an important role in the pathogenesis of MDS and AML. Alternatively spliced transcript variants encoding distinct isoforms have been reported. # PRDM16 in BAT Brown adipose tissue (BAT) oxidizes chemical energy to produce heat. This heat energy can act as a defense against hypothermia and obesity. PRDM16 is highly enriched in brown adipose cells as compared to white adipose cells, and plays a role in these thermogenic processes in brown adipose tissue. PRDM16 activates brown fat cell identity and can control the determination of brown adipose fate. A knock-out of PRDM16 in mice shows a loss of brown cell characteristics, showing that PRDM16 activity is important in determining brown adipose fate. Brown adipocytes consist of densely packed mitochondria that contain uncoupling protein 1 (UCP-1). UCP-1 plays a key role in brown adipocyte thermogenesis. The presence of PRDM16 in adipose tissue causes a significant up-regulation of thermogenic genes, such as UCP-1 and CIDEA, resulting in thermogenic heat production. Understanding and stimulating the thermogenic processes in brown adipocytes provides possible therapeutic options for treating obesity. # PRDM16 in WAT White adipose tissue (WAT) primarily stores excess energy in the form of triglycerides. Recent research has shown that PRDM16 is present in subcutaneous white adipose tissue. The activity of PRDM16 in white adipose tissue leads to the production of brown fat-like adipocytes within white adipose tissue, called beige cells (also called brite cells). These beige cells have a brown adipose tissue-like phenotype and actions, including thermogenic processes seen in BAT. In mice, the levels of PRDM16 within WAT, specifically anterior subcutaneous WAT and inguinal subcutaneous WAT, is about 50% that of interscapular BAT, both in protein expression and in mRNA quantity. This expression takes place primarily within mature adipocytes. Transgenic aP2-PRDM16 mice were used in a study to observe the effects of PRDM16 expression in WAT. The study found that the presence of PRDM16 in subcutaneous WAT leads to a significant up-regulation of brown-fat selective genes UCP-1, CIDEA, and PPARGC1A. This up-regulation lead to the development of a BAT-like phenotype within the white adipose tissue. Expression of PRDM16 has also been shown to protect against high-fat diet induced weight gain. Seale et al.’s experiment with aP2-PRDM16 transgenic mice and wild type mice showed that transgenic mice eating a 60% high-fat diet had significantly less weight gain than wild type mice on the same diet. Seale et al. determined the weight difference was not due to differences in food intake, as both transgenic and wild type mice were consuming the same amount of food on a daily basis. Rather, the weight difference stemmed from higher energy expenditure in the transgenic mice. Another of Seale et al.’s experiments showed the transgenic mice consumed a greater volume of oxygen over a 72-hour period than the wild type mice, showing a greater amount of energy expenditure in the transgenic mice. This energy expenditure in turn is attributed to PRDM16’s ability to up-regulate UCP-1 and CIDEA gene expression, resulting in thermogenesis. If human WAT expresses PRDM16 as in mice, this WAT could be a potential target for stimulating energy expenditure and combating obesity. # Notes - ↑ Mochizuki N, Shimizu S, Nagasawa T, Tanaka H, Taniwaki M, Yokota J, Morishita K (November 2000). "A novel gene, MEL1, mapped to 1p36.3 is highly homologous to the MDS1/EVI1 gene and is transcriptionally activated in t(1;3)(p36;q21)-positive leukemia cells". Blood. 96 (9): 3209–14. PMID 11050005..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} - ↑ Jump up to: 2.0 2.1 2.2 "Entrez Gene: PRDM16 PR domain containing 16". - ↑ Jump up to: 3.00 3.01 3.02 3.03 3.04 3.05 3.06 3.07 3.08 3.09 3.10 Patrick Seale; Heather M. Conroe; Jennifer Estall; Shingo Kajimura; Andrea Frontini; Jeff Ishibashi; Paul Cohen; Saverio Cinti & Bruce M. Spiegelman (January 2011). "Prdm16 determines the thermogenic program of subcutaneous white adipose tissue in mice". The Journal of Clinical Investigation. 121 (1): 96–105. doi:10.1172/JCI44271. PMC 3007155. - ↑ Seale P, Bjork B, Yang W, Kajimura S, Chin S, Kuang S, Scimè A, Devarakonda S, Conroe HM, Erdjument-Bromage H, Tempst P, Rudnicki MA, Beier DR, Spiegelman BM (August 2008). "PRDM16 controls a brown fat/skeletal muscle switch". Nature. 454 (7207): 961–7. doi:10.1038/nature07182. PMC 2583329. PMID 18719582. - ↑ Jump up to: 5.0 5.1 5.2 Patrick Seale; Shingo Kajimura; Wenli Yang; Sherry Chin; Lindsay Rohas; Marc Uldry; Geneviève Tavernier; Dominique Langin & Bruce M Spiegelman (July 2007). "Transcriptional Control of Brown Fat Determination by PRDM16". Cell Metabolism. 6 (1): 38–54. doi:10.1016/j.cmet.2007.06.001.	PRDM16 PR domain containing 16, also known as PRDM16, is a protein which in humans is encoded by the PRDM16 gene.[1][2] PRDM16 acts as a transcription coregulator that controls the development of brown adipocytes in brown adipose tissue.[3] Previously, this coregulator was believed to be present only in brown adipose tissue, but more recent studies have shown that PRDM16 is highly expressed in subcutaneous white adipose tissue as well.[3] # Function The protein encoded by this gene is a zinc finger transcription factor.[2] PRDM16 controls the cell fate between muscle and brown fat cells. Loss of PRDM16 from brown fat precursors causes a loss of brown fat characteristics and promotes muscle differentiation.[4] # Clinical significance The reciprocal translocation t(1;3)(p36;q21) occurs in a subset of myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). This gene is located near the 1p36.3 breakpoint and has been shown to be specifically expressed in the t(1:3)(p36,q21)-positive MDS/AML. The protein encoded by this gene contains an N-terminal PR domain. The translocation results in the overexpression of a truncated version of this protein that lacks the PR domain, which may play an important role in the pathogenesis of MDS and AML. Alternatively spliced transcript variants encoding distinct isoforms have been reported.[2] # PRDM16 in BAT Brown adipose tissue (BAT) oxidizes chemical energy to produce heat. This heat energy can act as a defense against hypothermia and obesity.[3] PRDM16 is highly enriched in brown adipose cells as compared to white adipose cells, and plays a role in these thermogenic processes in brown adipose tissue. PRDM16 activates brown fat cell identity and can control the determination of brown adipose fate. A knock-out of PRDM16 in mice shows a loss of brown cell characteristics, showing that PRDM16 activity is important in determining brown adipose fate.[5] Brown adipocytes consist of densely packed mitochondria that contain uncoupling protein 1 (UCP-1). UCP-1 plays a key role in brown adipocyte thermogenesis. The presence of PRDM16 in adipose tissue causes a significant up-regulation of thermogenic genes, such as UCP-1 and CIDEA, resulting in thermogenic heat production.[3] Understanding and stimulating the thermogenic processes in brown adipocytes provides possible therapeutic options for treating obesity.[5] # PRDM16 in WAT White adipose tissue (WAT) primarily stores excess energy in the form of triglycerides.[3][5] Recent research has shown that PRDM16 is present in subcutaneous white adipose tissue.[3] The activity of PRDM16 in white adipose tissue leads to the production of brown fat-like adipocytes within white adipose tissue, called beige cells (also called brite cells). These beige cells have a brown adipose tissue-like phenotype and actions, including thermogenic processes seen in BAT.[3] In mice, the levels of PRDM16 within WAT, specifically anterior subcutaneous WAT and inguinal subcutaneous WAT, is about 50% that of interscapular BAT, both in protein expression and in mRNA quantity.[3] This expression takes place primarily within mature adipocytes. Transgenic aP2-PRDM16 mice were used in a study to observe the effects of PRDM16 expression in WAT.[3] The study found that the presence of PRDM16 in subcutaneous WAT leads to a significant up-regulation of brown-fat selective genes UCP-1, CIDEA, and PPARGC1A. This up-regulation lead to the development of a BAT-like phenotype within the white adipose tissue. Expression of PRDM16 has also been shown to protect against high-fat diet induced weight gain.[3] Seale et al.’s experiment with aP2-PRDM16 transgenic mice and wild type mice showed that transgenic mice eating a 60% high-fat diet had significantly less weight gain than wild type mice on the same diet. Seale et al. determined the weight difference was not due to differences in food intake, as both transgenic and wild type mice were consuming the same amount of food on a daily basis. Rather, the weight difference stemmed from higher energy expenditure in the transgenic mice. Another of Seale et al.’s experiments showed the transgenic mice consumed a greater volume of oxygen over a 72-hour period than the wild type mice, showing a greater amount of energy expenditure in the transgenic mice.[3] This energy expenditure in turn is attributed to PRDM16’s ability to up-regulate UCP-1 and CIDEA gene expression, resulting in thermogenesis. If human WAT expresses PRDM16 as in mice, this WAT could be a potential target for stimulating energy expenditure and combating obesity. # Notes - ↑ Mochizuki N, Shimizu S, Nagasawa T, Tanaka H, Taniwaki M, Yokota J, Morishita K (November 2000). "A novel gene, MEL1, mapped to 1p36.3 is highly homologous to the MDS1/EVI1 gene and is transcriptionally activated in t(1;3)(p36;q21)-positive leukemia cells". Blood. 96 (9): 3209–14. PMID 11050005..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} - ↑ Jump up to: 2.0 2.1 2.2 "Entrez Gene: PRDM16 PR domain containing 16". - ↑ Jump up to: 3.00 3.01 3.02 3.03 3.04 3.05 3.06 3.07 3.08 3.09 3.10 Patrick Seale; Heather M. Conroe; Jennifer Estall; Shingo Kajimura; Andrea Frontini; Jeff Ishibashi; Paul Cohen; Saverio Cinti & Bruce M. Spiegelman (January 2011). "Prdm16 determines the thermogenic program of subcutaneous white adipose tissue in mice". The Journal of Clinical Investigation. 121 (1): 96–105. doi:10.1172/JCI44271. PMC 3007155. - ↑ Seale P, Bjork B, Yang W, Kajimura S, Chin S, Kuang S, Scimè A, Devarakonda S, Conroe HM, Erdjument-Bromage H, Tempst P, Rudnicki MA, Beier DR, Spiegelman BM (August 2008). "PRDM16 controls a brown fat/skeletal muscle switch". Nature. 454 (7207): 961–7. doi:10.1038/nature07182. PMC 2583329. PMID 18719582. - ↑ Jump up to: 5.0 5.1 5.2 Patrick Seale; Shingo Kajimura; Wenli Yang; Sherry Chin; Lindsay Rohas; Marc Uldry; Geneviève Tavernier; Dominique Langin & Bruce M Spiegelman (July 2007). "Transcriptional Control of Brown Fat Determination by PRDM16". Cell Metabolism. 6 (1): 38–54. doi:10.1016/j.cmet.2007.06.001.	https://www.wikidoc.org/index.php/PRDM16
b748f9fd11067445f63b7e187402f373e6742b89	wikidoc	PRIMA1	PRIMA1 Proline-rich membrane anchor 1, also known as PRiMA, is a protein that in humans is encoded by the PRIMA1 gene. # Function PRiMA functions to organize acetylcholinesterase (AChE) into tetramers, and to anchor AChE at neural cell membranes. This is accomplished by the proline rich anchor domain (PRAD) of PRIMA1 which anchors the tetramer of AChE into the plasma membrane of neural cells and myocytes. The PRAD interacts with the C-terminal T-peptide of AChE. PRiMA plays a role in targeting AChE to the cell surface and, in neuroblastoma cells, PRiMA the limiting factor of such targeting. In both mice and humans, PRiMA exists as two alternative splice variants that differ in their cytoplasmic regions. # Clinical significance The severity of neurogenerative diseases, such as Alzheimer’s, can be related to the degradation of AChE.	PRIMA1 Proline-rich membrane anchor 1, also known as PRiMA, is a protein that in humans is encoded by the PRIMA1 gene.[1][2] # Function PRiMA functions to organize acetylcholinesterase (AChE) into tetramers, and to anchor AChE at neural cell membranes.[1] This is accomplished by the proline rich anchor domain (PRAD) of PRIMA1 which anchors the tetramer of AChE into the plasma membrane of neural cells and myocytes.[3] The PRAD interacts with the C-terminal T-peptide of AChE.[4] PRiMA plays a role in targeting AChE to the cell surface and, in neuroblastoma cells, PRiMA the limiting factor of such targeting.[2] In both mice and humans, PRiMA exists as two alternative splice variants that differ in their cytoplasmic regions. # Clinical significance The severity of neurogenerative diseases, such as Alzheimer’s, can be related to the degradation of AChE.[5]	https://www.wikidoc.org/index.php/PRIMA1
e7e13ed64b3c935dba2fa7f47a496b801807521a	wikidoc	PRKAB1	PRKAB1 5'-AMP-activated protein kinase subunit beta-1 is an enzyme that in humans is encoded by the PRKAB1 gene. The protein encoded by this gene is a regulatory subunit of the AMP-activated protein kinase (AMPK). AMPK is a heterotrimer consisting of an alpha catalytic subunit, and non-catalytic beta and gamma subunits. AMPK is an important energy-sensing enzyme that monitors cellular energy status. In response to cellular metabolic stresses, AMPK is activated, and thus phosphorylates and inactivates acetyl-CoA carboxylase (ACC) and beta-hydroxy beta-methylglutaryl-CoA reductase (HMGCR), key enzymes involved in regulating de novo biosynthesis of fatty acid and cholesterol. This subunit may be a positive regulator of AMPK activity. The myristoylation and phosphorylation of this subunit have been shown to affect the enzyme activity and cellular localization of AMPK. This subunit may also serve as an adaptor molecule mediating the association of the AMPK complex. # Model organisms Model organisms have been used in the study of PRKAB1 function. A conditional knockout mouse line, called Prkab1tm1a(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. Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion. Twenty five tests were carried out on mutant mice and four significant abnormalities were observed. Homozygous mutant males displayed impaired glucose tolerance. Animals of both sex had increased circulating bilirubin levels, increased IgG3 levels, and a number of atypical haematology parameters. # Interactions PRKAB1 has been shown to interact with PRKAG2 and PRKAG1. The 5'-AMP-activated protein kinase beta subunit interaction domain (AMPKBI) is a conserved domain found in the beta subunit of the 5-AMP-activated protein kinase complex, and its yeast homologues Sip1 (SNF1-interacting protein 1), Sip2 (SNF1-interacting protein 2) and Gal83 (galactose metabolism 83), which are found in the SNF1 (sucrose non-fermenting) kinase complex. This region is sufficient for interaction of this subunit with the kinase complex, but is not solely responsible for the interaction, and the interaction partner is not known.	PRKAB1 5'-AMP-activated protein kinase subunit beta-1 is an enzyme that in humans is encoded by the PRKAB1 gene.[1][2] The protein encoded by this gene is a regulatory subunit of the AMP-activated protein kinase (AMPK). AMPK is a heterotrimer consisting of an alpha catalytic subunit, and non-catalytic beta and gamma subunits. AMPK is an important energy-sensing enzyme that monitors cellular energy status. In response to cellular metabolic stresses, AMPK is activated, and thus phosphorylates and inactivates acetyl-CoA carboxylase (ACC) and beta-hydroxy beta-methylglutaryl-CoA reductase (HMGCR), key enzymes involved in regulating de novo biosynthesis of fatty acid and cholesterol. This subunit may be a positive regulator of AMPK activity. The myristoylation and phosphorylation of this subunit have been shown to affect the enzyme activity and cellular localization of AMPK. This subunit may also serve as an adaptor molecule mediating the association of the AMPK complex.[2] # Model organisms Model organisms have been used in the study of PRKAB1 function. A conditional knockout mouse line, called Prkab1tm1a(KOMP)Wtsi[10][11] 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.[12][13][14] Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion.[8][15] Twenty five tests were carried out on mutant mice and four significant abnormalities were observed.[8] Homozygous mutant males displayed impaired glucose tolerance. Animals of both sex had increased circulating bilirubin levels, increased IgG3 levels, and a number of atypical haematology parameters.[8] # Interactions PRKAB1 has been shown to interact with PRKAG2[16] and PRKAG1.[16] The 5'-AMP-activated protein kinase beta subunit interaction domain (AMPKBI) is a conserved domain found in the beta subunit of the 5-AMP-activated protein kinase complex, and its yeast homologues Sip1 (SNF1-interacting protein 1), Sip2 (SNF1-interacting protein 2) and Gal83 (galactose metabolism 83), which are found in the SNF1 (sucrose non-fermenting) kinase complex.[17] This region is sufficient for interaction of this subunit with the kinase complex, but is not solely responsible for the interaction, and the interaction partner is not known.[18]	https://www.wikidoc.org/index.php/PRKAB1
f20810ec0eddada42dee22a18dcc98346637624f	wikidoc	PRKAB2	PRKAB2 5'-AMP-activated protein kinase subunit beta-2 is an enzyme that in humans is encoded by the PRKAB2 gene. The protein encoded by this gene is a regulatory subunit of the AMP-activated protein kinase (AMPK). AMPK is a heterotrimer consisting of an alpha catalytic subunit, and non-catalytic beta and gamma subunits. AMPK is an important energy-sensing enzyme that monitors cellular energy status. In response to cellular metabolic stresses, AMPK is activated, and thus phosphorylates and inactivates acetyl-CoA carboxylase (ACC) and beta-hydroxy beta-methylglutaryl-CoA reductase (HMGCR), key enzymes involved in regulating de novo biosynthesis of fatty acid and cholesterol. This subunit may be a positive regulator of AMPK activity. It is highly expressed in skeletal muscle and thus may have tissue-specific roles. # Related gene problems - 1q21.1 deletion syndrome - 1q21.1 duplication syndrome # Interactions PRKAB2 has been shown to interact with PRKAG2 and PRKAG1. Research on the genes CHD1L and PRKAB2 within lymphoblast cells lead to the conclusion that anomalies appear with the 1q21.1 deletion syndrome: - CHD1L is an enzyme which is involved in untangling the chromatids and the DNA repair system. With 1q21.1 deletion syndrome a disturbance occurs, which leads to increased DNA breaks. The role of CHD1L is similar to that of helicase with the Werner syndrome - PRKAB2 is involved in maintaining the energy level of cells. With 1q21.1-deletion syndrome this function was attenuated.	PRKAB2 5'-AMP-activated protein kinase subunit beta-2 is an enzyme that in humans is encoded by the PRKAB2 gene.[1][2] The protein encoded by this gene is a regulatory subunit of the AMP-activated protein kinase (AMPK). AMPK is a heterotrimer consisting of an alpha catalytic subunit, and non-catalytic beta and gamma subunits. AMPK is an important energy-sensing enzyme that monitors cellular energy status. In response to cellular metabolic stresses, AMPK is activated, and thus phosphorylates and inactivates acetyl-CoA carboxylase (ACC) and beta-hydroxy beta-methylglutaryl-CoA reductase (HMGCR), key enzymes involved in regulating de novo biosynthesis of fatty acid and cholesterol. This subunit may be a positive regulator of AMPK activity. It is highly expressed in skeletal muscle and thus may have tissue-specific roles.[2] # Related gene problems - 1q21.1 deletion syndrome - 1q21.1 duplication syndrome # Interactions PRKAB2 has been shown to interact with PRKAG2[3] and PRKAG1.[3] Research on the genes CHD1L and PRKAB2 within lymphoblast cells[4] lead to the conclusion that anomalies appear with the 1q21.1 deletion syndrome: - CHD1L is an enzyme which is involved in untangling the chromatids and the DNA repair system. With 1q21.1 deletion syndrome a disturbance occurs, which leads to increased DNA breaks. The role of CHD1L is similar to that of helicase with the Werner syndrome - PRKAB2 is involved in maintaining the energy level of cells. With 1q21.1-deletion syndrome this function was attenuated.	https://www.wikidoc.org/index.php/PRKAB2
79d9194e6b0bdef6d5b718aca20773cd65ab4e04	wikidoc	PRKACA	PRKACA The catalytic subunit α of protein kinase A is a key regulatory enzyme that in humans is encoded by the PRKACA gene. This enzyme is responsible for phosphorylating other proteins and substrates, changing their activity. Protein kinase A catalytic subunit (PKA Cα) is a member of the AGC kinase family (protein kinases A, G, and C), and contributes to the control of cellular processes that include glucose metabolism, cell division, and contextual memory. PKA Cα is part of a larger protein complex that is responsible for controlling when and where proteins are phosphorylated. Defective regulation of PKA holoenzyme activity has been linked to the progression of cardiovascular disease, certain endocrine disorders and cancers. # Discovery Edmond H. Fischer and Edwin G. Krebs at the University of Washington discovered PKA in the late 1950s while working through the mechanisms that govern glycogen phosphorylase. They realized that a key metabolic enzyme called phosphorylase kinase was activated by another kinase that was dependent on the second messenger cyclic AMP (cAMP). They named this new enzyme the cAMP-dependent protein kinase, and proceeded to purify and characterize this new enzyme. Fischer and Krebs won the Nobel Prize in Physiology or Medicine in 1992 for this discovery and their continued work on kinases, and their counterparts the protein phosphatases. Today, this cAMP-dependent protein kinase is more simply noted as PKA. Another key event in the history of PKA occurred when Susan Taylor and Janusz Sowadski at the University of California San Diego solved the three dimensional structure of the catalytic subunit of the enzyme. It was also realized that inside cells, PKA catalytic subunits are found in complex with regulatory subunits and inhibitor proteins that block the activity of the enzyme. An additional facet of PKA action that was pioneered by John Scott at the University of Washington and Kjetil Tasken at the University of Oslo is that the enzyme is tethered within the cell through its association with a family of A-kinase-anchoring proteins (AKAPs). This led to the hypothesis that the subcellular localization of anchored PKA controls what proteins are regulated by the kinase. # Catalytic subunits PRKACA is found on chromosome 19 in humans. There are two well-described transcripts of this gene, arising from alternative splicing events. The most common form, called Cα1, is expressed throughout human tissue. Another transcript, called Cα2, is found primarily in sperm cells and differs from Cα1 only in the first 15 amino acids. In addition, there are two other isoforms of the catalytic subunit of PKA called Cβ and Cγ arising from different genes but have similar functions as Cα. Cβ is found abundantly in the brain and in lower levels in other tissues, while Cγ is most likely expressed in the testis. # Signaling Inactive PKA holoenzyme exists as a tetramer composed of two regulatory (R) subunits and two catalytic (C) subunits. Biochemical studies demonstrated that there are two types of R subunits. The type I R subunits of which there are two isoforms (RIα, and RIβ) bind the catalytic subunits to create the type I PKA holoenzyme. Likewise type II R subunits, of which there are two isoforms (RIIα, and RIIβ), create the type II PKA holoenzyme. In the presence of cAMP, each R subunit binds 2 cAMP molecules and causes a conformational change in the R subunits that releases the C subunits to phosphorylate downstream substrates. The different R subunits differ in their sensitivity to cAMP, expression levels and subcellular locations. A-kinase-anchoring proteins (AKAPs) bind a surface formed between both R subunits and target the kinase to different locations in the cell. This optimizes where and when cellular communication occurs within the cell. # Clinical significance Protein kinase A has been implicated in a number of diseases, including cardiovascular disease, tumors of the adrenal cortex, and cancer. It has been speculated that abnormally high levels of PKA phosphorylation contributes to heart disease. This affects excitation-contraction coupling, which is a rhythmic process that controls the contraction of cardiac muscle through the synchronized actions of calcium and cAMP responsive enzymes. There is also evidence to support that the mis-localization of PKA signaling contributes to cardiac arrhythmias, specifically Long QT syndrome. This results in irregular heartbeats that can cause sudden death. Mutations in the PRKACA gene that promote abnormal enzyme activity have been linked to disease of the adrenal gland. Several mutations in PRKACA have been found in patients with Cushing’s syndrome that result in an increase in the ability of PKA to broadly phosphorylate other proteins. One mutation in the PRKACA gene that causes an amino acid substitution of leucine to arginine in position 206, was found in over 60% of patients with adrenocortical tumors. Other mutations and genetic alterations in the PRKACA gene have been identified in adrenocortical adenomas that also disrupt PKA signaling, leading to aberrant PKA phosphorylation. The Cα gene has also been incriminated in a variety of cancers, including colon, renal, rectal, prostate, lung, breast, adrenal carcinomas and lymphomas. There is recent and growing interest in fibrolamellar hepatocellular carcinoma. The molecular basis for this rare form of liver cancer that afflicts young adults is a genetic deletion on chromosome 19. The loss of DNA has been found in a very high percent of patients. The consequence of this deletion is the abnormal fusion of two genes- DNAJB1, which is the gene that codes for the heat shock protein 40 (Hsp40), and PRKACA. Further analyses of fibrolamellar hepatocellular carcinoma tissues show an increase in protein levels of this DNAJ-PKAc fusion protein. This is consistent with the hypothesis that increased kinase in liver tissues can initiate or perpetuate this rare form of liver cancer. Given the wealth of information on the three dimensional structures of DNAJ and PKA Cα there is some hope that new drugs can be developed to target this atypical and potentially tumorigenic fusion kinase. # Notes	PRKACA The catalytic subunit α of protein kinase A is a key regulatory enzyme that in humans is encoded by the PRKACA gene.[1] This enzyme is responsible for phosphorylating other proteins and substrates, changing their activity. Protein kinase A catalytic subunit (PKA Cα) is a member of the AGC kinase family (protein kinases A, G, and C), and contributes to the control of cellular processes that include glucose metabolism, cell division, and contextual memory.[2][3][4] PKA Cα is part of a larger protein complex that is responsible for controlling when and where proteins are phosphorylated. Defective regulation of PKA holoenzyme activity has been linked to the progression of cardiovascular disease, certain endocrine disorders and cancers. # Discovery Edmond H. Fischer and Edwin G. Krebs at the University of Washington discovered PKA in the late 1950s while working through the mechanisms that govern glycogen phosphorylase. They realized that a key metabolic enzyme called phosphorylase kinase was activated by another kinase that was dependent on the second messenger cyclic AMP (cAMP).[5] They named this new enzyme the cAMP-dependent protein kinase, and proceeded to purify and characterize this new enzyme. Fischer and Krebs won the Nobel Prize in Physiology or Medicine in 1992 for this discovery and their continued work on kinases, and their counterparts the protein phosphatases. Today, this cAMP-dependent protein kinase is more simply noted as PKA. Another key event in the history of PKA occurred when Susan Taylor and Janusz Sowadski at the University of California San Diego solved the three dimensional structure of the catalytic subunit of the enzyme.[6] It was also realized that inside cells, PKA catalytic subunits are found in complex with regulatory subunits and inhibitor proteins that block the activity of the enzyme. An additional facet of PKA action that was pioneered by John Scott at the University of Washington and Kjetil Tasken at the University of Oslo is that the enzyme is tethered within the cell through its association with a family of A-kinase-anchoring proteins (AKAPs). This led to the hypothesis that the subcellular localization of anchored PKA controls what proteins are regulated by the kinase.[7] # Catalytic subunits PRKACA is found on chromosome 19 in humans.[1] There are two well-described transcripts of this gene, arising from alternative splicing events. The most common form, called Cα1, is expressed throughout human tissue. Another transcript, called Cα2, is found primarily in sperm cells and differs from Cα1 only in the first 15 amino acids.[8] In addition, there are two other isoforms of the catalytic subunit of PKA called Cβ and Cγ arising from different genes but have similar functions as Cα.[9][10] Cβ is found abundantly in the brain and in lower levels in other tissues, while Cγ is most likely expressed in the testis. # Signaling Inactive PKA holoenzyme exists as a tetramer composed of two regulatory (R) subunits and two catalytic (C) subunits.[11] Biochemical studies demonstrated that there are two types of R subunits. The type I R subunits of which there are two isoforms (RIα, and RIβ) bind the catalytic subunits to create the type I PKA holoenzyme. Likewise type II R subunits, of which there are two isoforms (RIIα, and RIIβ), create the type II PKA holoenzyme. In the presence of cAMP, each R subunit binds 2 cAMP molecules and causes a conformational change in the R subunits that releases the C subunits to phosphorylate downstream substrates.[12] The different R subunits differ in their sensitivity to cAMP, expression levels and subcellular locations. A-kinase-anchoring proteins (AKAPs) bind a surface formed between both R subunits and target the kinase to different locations in the cell. This optimizes where and when cellular communication occurs within the cell.[7] # Clinical significance Protein kinase A has been implicated in a number of diseases, including cardiovascular disease, tumors of the adrenal cortex, and cancer. It has been speculated that abnormally high levels of PKA phosphorylation contributes to heart disease. This affects excitation-contraction coupling, which is a rhythmic process that controls the contraction of cardiac muscle through the synchronized actions of calcium and cAMP responsive enzymes.[13] There is also evidence to support that the mis-localization of PKA signaling contributes to cardiac arrhythmias, specifically Long QT syndrome. This results in irregular heartbeats that can cause sudden death. Mutations in the PRKACA gene that promote abnormal enzyme activity have been linked to disease of the adrenal gland. Several mutations in PRKACA have been found in patients with Cushing’s syndrome that result in an increase in the ability of PKA to broadly phosphorylate other proteins. One mutation in the PRKACA gene that causes an amino acid substitution of leucine to arginine in position 206, was found in over 60% of patients with adrenocortical tumors.[14] Other mutations and genetic alterations in the PRKACA gene have been identified in adrenocortical adenomas that also disrupt PKA signaling, leading to aberrant PKA phosphorylation. The Cα gene has also been incriminated in a variety of cancers, including colon, renal, rectal, prostate, lung, breast, adrenal carcinomas and lymphomas. There is recent and growing interest in fibrolamellar hepatocellular carcinoma. The molecular basis for this rare form of liver cancer that afflicts young adults is a genetic deletion on chromosome 19. The loss of DNA has been found in a very high percent of patients.[15] The consequence of this deletion is the abnormal fusion of two genes- DNAJB1, which is the gene that codes for the heat shock protein 40 (Hsp40), and PRKACA. Further analyses of fibrolamellar hepatocellular carcinoma tissues show an increase in protein levels of this DNAJ-PKAc fusion protein. This is consistent with the hypothesis that increased kinase in liver tissues can initiate or perpetuate this rare form of liver cancer. Given the wealth of information on the three dimensional structures of DNAJ and PKA Cα there is some hope that new drugs can be developed to target this atypical and potentially tumorigenic fusion kinase. # Notes	https://www.wikidoc.org/index.php/PRKACA
9ef8917c5a34950bde9376917371a0d4c2e554d6	wikidoc	PRKACB	PRKACB cAMP-dependent protein kinase catalytic subunit beta is an enzyme that in humans is encoded by the PRKACB gene. cAMP is a signaling molecule important for a variety of cellular functions. cAMP exerts its effects by activating the protein kinase A (PKA), which transduces the signal through phosphorylation of different target proteins. The inactive holoenzyme of PKA is a tetramer composed of two regulatory and two catalytic subunits. cAMP causes the dissociation of the inactive holoenzyme into a dimer of regulatory subunits bound to four cAMP and two free monomeric catalytic subunits. Four different regulatory subunits and three catalytic subunits of PKA have been identified in humans. The protein encoded by this gene is a member of the serine/threonine protein kinase family and is a catalytic subunit of PKA. Three alternatively spliced transcript variants encoding distinct isoforms have been observed. # Interactions PRKACB has been shown to interact with Ryanodine receptor 2 and Low affinity nerve growth factor receptor.	PRKACB cAMP-dependent protein kinase catalytic subunit beta is an enzyme that in humans is encoded by the PRKACB gene.[1] cAMP is a signaling molecule important for a variety of cellular functions. cAMP exerts its effects by activating the protein kinase A (PKA), which transduces the signal through phosphorylation of different target proteins. The inactive holoenzyme of PKA is a tetramer composed of two regulatory and two catalytic subunits. cAMP causes the dissociation of the inactive holoenzyme into a dimer of regulatory subunits bound to four cAMP and two free monomeric catalytic subunits. Four different regulatory subunits and three catalytic subunits of PKA have been identified in humans. The protein encoded by this gene is a member of the serine/threonine protein kinase family and is a catalytic subunit of PKA. Three alternatively spliced transcript variants encoding distinct isoforms have been observed.[1] # Interactions PRKACB has been shown to interact with Ryanodine receptor 2[2] and Low affinity nerve growth factor receptor.[3]	https://www.wikidoc.org/index.php/PRKACB
8377b35f1b3473e9708a71aeef22b2864c189f2c	wikidoc	PRKCB1	PRKCB1 Protein kinase C beta type is an enzyme that in humans is encoded by the PRKCB gene. Protein kinase C (PKC) is a family of serine- and threonine-specific protein kinases that can be activated by calcium and second messenger diacylglycerol. PKC family members phosphorylate a wide variety of protein targets and are known to be involved in diverse cellular signaling pathways. PKC family members also serve as major receptors for phorbol esters, a class of tumor promoters. Each member of the PKC family has a specific expression profile and is believed to play a distinct role in cells. The protein encoded by this gene is one of the PKC family members. This protein kinase has been reported to be involved in many different cellular functions, such as B cell activation, apoptosis induction, endothelial cell proliferation, and intestinal sugar absorption. Studies in mice also suggest that this kinase may also regulate neuronal functions and correlate fear-induced conflict behavior after stress. Alternatively spliced transcript variants encoding distinct isoforms have been reported. This gene could be associated with autism. # Interactions PRKCB1 has been shown to interact with RIPK4, beta adrenergic receptor kinase, PDLIM5 and GNB2L1.	PRKCB1 Protein kinase C beta type is an enzyme that in humans is encoded by the PRKCB gene.[1] Protein kinase C (PKC) is a family of serine- and threonine-specific protein kinases that can be activated by calcium and second messenger diacylglycerol. PKC family members phosphorylate a wide variety of protein targets and are known to be involved in diverse cellular signaling pathways. PKC family members also serve as major receptors for phorbol esters, a class of tumor promoters. Each member of the PKC family has a specific expression profile and is believed to play a distinct role in cells. The protein encoded by this gene is one of the PKC family members. This protein kinase has been reported to be involved in many different cellular functions, such as B cell activation, apoptosis induction, endothelial cell proliferation, and intestinal sugar absorption. Studies in mice also suggest that this kinase may also regulate neuronal functions and correlate fear-induced conflict behavior after stress. Alternatively spliced transcript variants encoding distinct isoforms have been reported.[2] This gene could be associated with autism.[3][4] # Interactions PRKCB1 has been shown to interact with RIPK4,[5] beta adrenergic receptor kinase,[6] PDLIM5[7] and GNB2L1.[8]	https://www.wikidoc.org/index.php/PRKCB1
addbb2f1a80e5d9807a0a982e8b9a312893724ed	wikidoc	PRPF31	PRPF31 PRP31 pre-mRNA processing factor 31 homolog (S. cerevisiae), also known as PRPF31, is a protein which in humans is encoded by the PRPF31 gene. # Function PRPF31 is the gene coding for the splicing factor hPRP31. It is essential for the formation of the spliceosome hPRP31 is associated with the U4/U6 di-snRNP and interacts with another splicing factor, hPRP6, to form the U4/U6-U5 tri-snRNP. It has been shown that when hPRP31 is knocked down by RNAi, U4/U6 di-snRNPs accumulate in the Cajal bodies and the U4/U6-U5 tri-snRNP cannot form. PRPF31 is recruited to introns following the attachment of U4 and U6 RNAs and the 15.5K protein NHP2L1. The addition of PRPF31 is crucial for the transition of the spliceosomal complex to the activated state. # Clinical significance A mutation in PRPF31 is one of 4 known mutations in splicing factors which are known to cause retinitis pigmentosa. The first mutation in PRPF31 was discovered by Vithana et al. in 2001. Retinitis pigmentosa (RP) is a clinically and genetically heterogeneous group of retinal dystrophies characterized by a progressive degeneration of photoreceptors, eventually resulting in severe visual impairment. # Inheritance Mutations in PRPF31 are inherited in an autosomal dominant manner, accounting for 2.5% of cases of autosomal dominant retinitis pigmentosa (adRP) in a mixed UK population. However, the inheritance pattern of PRPF31 mutations is atypical of dominant inheritance, showing the phenomenon of partial penetrance, whereby a dominant mutations appear to "skip" generations. This is thought to be due to the presence of two wild type alleles, a high-expressivity allele and a low-expressivity allele. If a patient has a mutant allele and a high-expressivity allele, they do not show disease phenotype. If a patient has a mutant allele and a low-expressivity allele, the residual level of protein falls beneath the threahold for normal function, and so they do show disease phenotype. The inheritance pattern of PRPF31 can therefore be thought of as a variation of haploinsufficiency. This variant of haploinsufficiency is only seen in two other human diseases: Erythropoietic protoporphyria, caused by mutations in the FECH gene; and hereditary elliptocytosis, caused by mutations in the spectrin gene.	PRPF31 PRP31 pre-mRNA processing factor 31 homolog (S. cerevisiae), also known as PRPF31, is a protein which in humans is encoded by the PRPF31 gene.[1] # Function PRPF31 is the gene coding for the splicing factor hPRP31. It is essential for the formation of the spliceosome hPRP31 is associated with the U4/U6 di-snRNP and interacts with another splicing factor, hPRP6, to form the U4/U6-U5 tri-snRNP. It has been shown that when hPRP31 is knocked down by RNAi, U4/U6 di-snRNPs accumulate in the Cajal bodies and the U4/U6-U5 tri-snRNP cannot form.[2] PRPF31 is recruited to introns following the attachment of U4 and U6 RNAs and the 15.5K protein NHP2L1. The addition of PRPF31 is crucial for the transition of the spliceosomal complex to the activated state.[3] # Clinical significance A mutation in PRPF31 is one of 4 known mutations in splicing factors which are known to cause retinitis pigmentosa. The first mutation in PRPF31 was discovered by Vithana et al. in 2001.[1] Retinitis pigmentosa (RP) is a clinically and genetically heterogeneous group of retinal dystrophies characterized by a progressive degeneration of photoreceptors, eventually resulting in severe visual impairment.[4] # Inheritance Mutations in PRPF31 are inherited in an autosomal dominant manner, accounting for 2.5% of cases of autosomal dominant retinitis pigmentosa (adRP) in a mixed UK population.[5] However, the inheritance pattern of PRPF31 mutations is atypical of dominant inheritance, showing the phenomenon of partial penetrance, whereby a dominant mutations appear to "skip" generations. This is thought to be due to the presence of two wild type alleles, a high-expressivity allele and a low-expressivity allele. If a patient has a mutant allele and a high-expressivity allele, they do not show disease phenotype. If a patient has a mutant allele and a low-expressivity allele, the residual level of protein falls beneath the threahold for normal function, and so they do show disease phenotype. The inheritance pattern of PRPF31 can therefore be thought of as a variation of haploinsufficiency. This variant of haploinsufficiency is only seen in two other human diseases: Erythropoietic protoporphyria, caused by mutations in the FECH gene; and hereditary elliptocytosis, caused by mutations in the spectrin gene.[6][7]	https://www.wikidoc.org/index.php/PRPF31
9cef4377e35e89c78ce67c48ad283b3b0fadb2d5	wikidoc	PRSS56	PRSS56 Putative serine protease 56 (PRSS56) is a serine protease that has been implicated in human eye development. # Genomics The gene is located on long arm of chromosome 2 (2q37.1). The encoded protein is 603 amino acid residues in length with a predicted molecular weight of 64 597 Daltons. The protein contains a peptidase S1 domain and possesses trypsin like serine protease activity. # Clinical Mutations in this gene are a cause of autosomal recessive posterior microphthalmos. The clinical features of this condition include extreme hyperopia due to short axial length with essentially normal anterior segment, steep corneal curvatures, shallow anterior chamber, thick lenses and thickened scleral walls. The palpebral fissures appear narrow because of relatively deep set eyes. Visual acuity is mildly to moderately reduced, and anisometropic or strabismic amblyopia is common. The fundus of the eye shows crowded optical discs, tortuous vessels and an abnormal foveal avascular zone. # Disease Model Mice homozygous for an ENU induced mutation show increased intraocular pressure, reduction in eye axial length, and narrow iridocorneal angles. Eyes from individuals with angle-closure glaucoma (ACG) often have a modestly decreased axial length, shallow anterior chamber and relatively large lens, features that predispose to angle closure. Homozygous mice model ACG.	PRSS56 Putative serine protease 56 (PRSS56) is a serine protease that has been implicated in human eye development. # Genomics The gene is located on long arm of chromosome 2 (2q37.1). The encoded protein is 603 amino acid residues in length with a predicted molecular weight of 64 597 Daltons. The protein contains a peptidase S1 domain and possesses trypsin like serine protease activity. # Clinical Mutations in this gene are a cause of autosomal recessive posterior microphthalmos.[1][2][3] The clinical features of this condition include extreme hyperopia due to short axial length with essentially normal anterior segment, steep corneal curvatures, shallow anterior chamber, thick lenses and thickened scleral walls. The palpebral fissures appear narrow because of relatively deep set eyes. Visual acuity is mildly to moderately reduced, and anisometropic or strabismic amblyopia is common. The fundus of the eye shows crowded optical discs, tortuous vessels and an abnormal foveal avascular zone. # Disease Model Mice homozygous for an ENU induced mutation show increased intraocular pressure, reduction in eye axial length, and narrow iridocorneal angles. Eyes from individuals with angle-closure glaucoma (ACG) often have a modestly decreased axial length, shallow anterior chamber and relatively large lens, features that predispose to angle closure. Homozygous mice model ACG.[2]	https://www.wikidoc.org/index.php/PRSS56
00169c1f8a2280e394ccbbe8b8b16118fc308f3c	wikidoc	PSMB10	PSMB10 Proteasome subunit beta type-10 as known as 20S proteasome subunit beta-2i is a protein that in humans is encoded by the PSMB10 gene. This protein has a major role in the immune system as part of an immunoproteasome that is primarily induced upon infection and formed by replacing constitutive beta subunits with inducible beta subunits which possess specific cleavage properties that aid in the release of peptides necessary for MHC class I antigen presentation. The immunoproteasome appears to have a pivotal role in modulating NFκB signaling. # Structure ## Gene This gene PSMB10 encodes a member of the proteasome B-type family, also known as the T1B family, that is a 20S core beta subunit. Proteolytic processing is required to generate a mature subunit. Expression of this gene is induced by gamma interferon, and this gene product replaces catalytic subunit beta2 (proteasome subunit beta type-7) in the immunoproteasome. The human PSMB10 gene has 8 exons and locates at chromosome band 16q22.1. ## Protein structure The human protein proteasome subunit beta type-8 is 25 kDa in size and composed of 234 amino acids. The calculated theoretical pI of this protein is 6.07. ## Complex assembly Proteasome subunit beta type-10 is one of the 17 essential subunits (alpha subunits 1-7, constitutive beta subunits 1-7, and inducible subunits including beta1i, beta2i, beta5i) that contributes to the complete assembly of 20S proteasome complex. In particular, proteasome subunit beta-2i, along with other beta subunits, assemble into two heptameric rings and subsequently a proteolytic chamber for substrate degradation. This protein contains "Trypsin-like" activity and is capable of cleaving after basic residues of peptide. The eukaryotic proteasome recognized degradable proteins, including damaged proteins for protein quality control purpose or key regulatory protein components for dynamic biological processes. The constitutive subunit beta1, beta2, and beta 5 (systematic nomenclature) can be replaced by their inducible counterparts beta1i, 2i, and 5i when cells are under the treatment of interferon-γ. The resulting proteasome complex becomes the so-called immunoproteasome. An essential function of the modified proteasome complex, the immunoproteasome, is the processing of numerous MHC class-I restricted T cell epitopes. The proteasome is a multicatalytic proteinase complex with a highly ordered 20S core structure. This barrel-shaped core structure is composed of 4 axially stacked rings of 28 non-identical subunits: the two end rings are each formed by 7 alpha subunits, and the two central rings are each formed by 7 beta subunits. Three beta subunits (beta1, beta2, beta5) each contains a proteolytic active site and has distinct substrate preferences. Proteasomes are distributed throughout eukaryotic cells at a high concentration and cleave peptides in an ATP/ubiquitin-dependent process in a non-lysosomal pathway. # Function Protein functions are supported by its tertiary structure and its interaction with associating partners. As one of 28 subunits of 20S proteasome, protein proteasome subunit beta type-2 contributes to form a proteolytic environment for substrate degradation. Evidences of the crystal structures of isolated 20S proteasome complex demonstrate that the two rings of beta subunits form a proteolytic chamber and maintain all their active sites of proteolysis within the chamber. Concomitantly, the rings of alpha subunits form the entrance for substrates entering the proteolytic chamber. In an inactivated 20S proteasome complex, the gate into the internal proteolytic chamber are guarded by the N-terminal tails of specific alpha-subunit. This unique structure design prevents random encounter between proteolytic active sites and protein substrate, which makes protein degradation a well-regulated process. 20S proteasome complex, by itself, is usually functionally inactive. The proteolytic capacity of 20S core particle (CP) can be activated when CP associates with one or two regulatory particles (RP) on one or both side of alpha rings. These regulatory particles include 19S proteasome complexes, 11S proteasome complex, etc. Following the CP-RP association, the confirmation of certain alpha subunits will change and consequently cause the opening of substrate entrance gate. Besides RPs, the 20S proteasomes can also be effectively activated by other mild chemical treatments, such as exposure to low levels of sodium dodecylsulfate (SDS) or NP-14. The 20S proteasome subunit beta-2i (systematic nomenclature) is originally expressed as a precursor with 273 amino acids. The fragment of 39 amino acids at peptide N-terminal is essential for proper protein folding and subsequent complex assembly. At the end-stage of complex assembly, the N-terminal fragment of beta2i subunit is cleaved, forming the mature beta2i subunit of 20S complex. During the basal assembly, and proteolytic processing is required to generate a mature subunit. The subunit beta5i only presents in the immunoproteasome and is replaced by subunit beta5(proteasome beta 5 subunit) in constitutive 20S proteasome complex. This protein has an important function in the immune system as part of an immunoproteasome which possess specific cleavage properties that aid in the release of peptides necessary for MHC class I antigen presentation. # Clinical significance The Proteasome and its subunits are of clinical significance for at least two reasons: (1) a compromised complex assembly or a dysfunctional proteasome can be associated with the underlying pathophysiology of specific diseases, and (2) they can be exploited as drug targets for therapeutic interventions. More recently, more effort has been made to consider the proteasome for the development of novel diagnostic markers and strategies. An improved and comprehensive understanding of the pathophysiology of the proteasome should lead to clinical applications in the future. The proteasomes form a pivotal component for the Ubiquitin-Proteasome System (UPS) and corresponding cellular Protein Quality Control (PQC). Protein ubiquitination and subsequent proteolysis and degradation by the proteasome are important mechanisms in the regulation of the cell cycle, cell growth and differentiation, gene transcription, signal transduction and apoptosis. Subsequently, a compromised proteasome complex assembly and function lead to reduced proteolytic activities and the accumulation of damaged or misfolded protein species. Such protein accumulation may contribute to the pathogenesis and phenotypic characteristics in neurodegenerative diseases, cardiovascular diseases, inflammatory responses and autoimmune diseases, and systemic DNA damage responses leading to malignancies. Several experimental and clinical studies have indicated that aberrations and deregulations of the UPS contribute to the pathogenesis of several neurodegenerative and myodegenerative disorders, including Alzheimer's disease, Parkinson's disease and Pick's disease, Amyotrophic lateral sclerosis (ALS), Huntington's disease, Creutzfeldt–Jakob disease, and motor neuron diseases, polyglutamine (PolyQ) diseases, Muscular dystrophies and several rare forms of neurodegenerative diseases associated with dementia. As part of the Ubiquitin-Proteasome System (UPS), the proteasome maintains cardiac protein homeostasis and thus plays a significant role in cardiac Ischemic injury, ventricular hypertrophy and Heart failure. Additionally, evidence is accumulating that the UPS plays an essential role in malignant transformation. UPS proteolysis plays a major role in responses of cancer cells to stimulatory signals that are critical for the development of cancer. Accordingly, gene expression by degradation of transcription factors, such as p53, c-Jun, c-Fos, NF-κB, c-Myc, HIF-1α, MATα2, STAT3, sterol-regulated element-binding proteins and androgen receptors are all controlled by the UPS and thus involved in the development of various malignancies. Moreover, the UPS regulates the degradation of tumor suppressor gene products such as adenomatous polyposis coli (APC) in colorectal cancer, retinoblastoma (Rb). and von Hippel-Lindau tumor suppressor (VHL), as well as a number of proto-oncogenes (Raf, Myc, Myb, Rel, Src, Mos, Abl). The UPS is also involved in the regulation of inflammatory responses. This activity is usually attributed to the role of proteasomes in the activation of NF-κB which further regulates the expression of pro inflammatory cytokines such as TNF-α, IL-β, IL-8, adhesion molecules (ICAM-1, VCAM-1, P-selectin) and prostaglandins and nitric oxide (NO). Additionally, the UPS also plays a role in inflammatory responses as regulators of leukocyte proliferation, mainly through proteolysis of cyclines and the degradation of CDK inhibitors. Lastly, autoimmune disease patients with SLE, Sjogren's syndrome and rheumatoid arthritis (RA) predominantly exhibit circulating proteasomes which can be applied as clinical biomarkers. During the antigen processing for the major histocompatibility complex (MHC) class-I, the proteasome is the major degradation machinery that degrades the antigen and present the resulting peptides to cytotoxic T lymphocytes. The immunoproteasome has been considered playing a critical role in improving the quality and quantity of generated class-I ligands.	PSMB10 Proteasome subunit beta type-10 as known as 20S proteasome subunit beta-2i is a protein that in humans is encoded by the PSMB10 gene.[1] This protein has a major role in the immune system as part of an immunoproteasome that is primarily induced upon infection and formed by replacing constitutive beta subunits with inducible beta subunits which possess specific cleavage properties that aid in the release of peptides necessary for MHC class I antigen presentation.[2] The immunoproteasome appears to have a pivotal role in modulating NFκB signaling.[3] # Structure ## Gene This gene PSMB10 encodes a member of the proteasome B-type family, also known as the T1B family, that is a 20S core beta subunit. Proteolytic processing is required to generate a mature subunit. Expression of this gene is induced by gamma interferon, and this gene product replaces catalytic subunit beta2 (proteasome subunit beta type-7) in the immunoproteasome.[4] The human PSMB10 gene has 8 exons and locates at chromosome band 16q22.1. ## Protein structure The human protein proteasome subunit beta type-8 is 25 kDa in size and composed of 234 amino acids. The calculated theoretical pI of this protein is 6.07. ## Complex assembly Proteasome subunit beta type-10 is one of the 17 essential subunits (alpha subunits 1-7, constitutive beta subunits 1-7, and inducible subunits including beta1i, beta2i, beta5i) that contributes to the complete assembly of 20S proteasome complex. In particular, proteasome subunit beta-2i, along with other beta subunits, assemble into two heptameric rings and subsequently a proteolytic chamber for substrate degradation. This protein contains "Trypsin-like" activity and is capable of cleaving after basic residues of peptide.[5] The eukaryotic proteasome recognized degradable proteins, including damaged proteins for protein quality control purpose or key regulatory protein components for dynamic biological processes. The constitutive subunit beta1, beta2, and beta 5 (systematic nomenclature) can be replaced by their inducible counterparts beta1i, 2i, and 5i when cells are under the treatment of interferon-γ. The resulting proteasome complex becomes the so-called immunoproteasome. An essential function of the modified proteasome complex, the immunoproteasome, is the processing of numerous MHC class-I restricted T cell epitopes.[6] The proteasome is a multicatalytic proteinase complex with a highly ordered 20S core structure. This barrel-shaped core structure is composed of 4 axially stacked rings of 28 non-identical subunits: the two end rings are each formed by 7 alpha subunits, and the two central rings are each formed by 7 beta subunits. Three beta subunits (beta1, beta2, beta5) each contains a proteolytic active site and has distinct substrate preferences. Proteasomes are distributed throughout eukaryotic cells at a high concentration and cleave peptides in an ATP/ubiquitin-dependent process in a non-lysosomal pathway.[7][8] # Function Protein functions are supported by its tertiary structure and its interaction with associating partners. As one of 28 subunits of 20S proteasome, protein proteasome subunit beta type-2 contributes to form a proteolytic environment for substrate degradation. Evidences of the crystal structures of isolated 20S proteasome complex demonstrate that the two rings of beta subunits form a proteolytic chamber and maintain all their active sites of proteolysis within the chamber.[8] Concomitantly, the rings of alpha subunits form the entrance for substrates entering the proteolytic chamber. In an inactivated 20S proteasome complex, the gate into the internal proteolytic chamber are guarded by the N-terminal tails of specific alpha-subunit. This unique structure design prevents random encounter between proteolytic active sites and protein substrate, which makes protein degradation a well-regulated process.[9][10] 20S proteasome complex, by itself, is usually functionally inactive. The proteolytic capacity of 20S core particle (CP) can be activated when CP associates with one or two regulatory particles (RP) on one or both side of alpha rings. These regulatory particles include 19S proteasome complexes, 11S proteasome complex, etc. Following the CP-RP association, the confirmation of certain alpha subunits will change and consequently cause the opening of substrate entrance gate. Besides RPs, the 20S proteasomes can also be effectively activated by other mild chemical treatments, such as exposure to low levels of sodium dodecylsulfate (SDS) or NP-14.[10][11] The 20S proteasome subunit beta-2i (systematic nomenclature) is originally expressed as a precursor with 273 amino acids. The fragment of 39 amino acids at peptide N-terminal is essential for proper protein folding and subsequent complex assembly. At the end-stage of complex assembly, the N-terminal fragment of beta2i subunit is cleaved, forming the mature beta2i subunit of 20S complex.[12] During the basal assembly, and proteolytic processing is required to generate a mature subunit. The subunit beta5i only presents in the immunoproteasome and is replaced by subunit beta5(proteasome beta 5 subunit) in constitutive 20S proteasome complex. This protein has an important function in the immune system as part of an immunoproteasome which possess specific cleavage properties that aid in the release of peptides necessary for MHC class I antigen presentation.[2] # Clinical significance The Proteasome and its subunits are of clinical significance for at least two reasons: (1) a compromised complex assembly or a dysfunctional proteasome can be associated with the underlying pathophysiology of specific diseases, and (2) they can be exploited as drug targets for therapeutic interventions. More recently, more effort has been made to consider the proteasome for the development of novel diagnostic markers and strategies. An improved and comprehensive understanding of the pathophysiology of the proteasome should lead to clinical applications in the future. The proteasomes form a pivotal component for the Ubiquitin-Proteasome System (UPS) [13] and corresponding cellular Protein Quality Control (PQC). Protein ubiquitination and subsequent proteolysis and degradation by the proteasome are important mechanisms in the regulation of the cell cycle, cell growth and differentiation, gene transcription, signal transduction and apoptosis.[14] Subsequently, a compromised proteasome complex assembly and function lead to reduced proteolytic activities and the accumulation of damaged or misfolded protein species. Such protein accumulation may contribute to the pathogenesis and phenotypic characteristics in neurodegenerative diseases,[15][16] cardiovascular diseases,[17][18][19] inflammatory responses and autoimmune diseases,[20] and systemic DNA damage responses leading to malignancies.[21] Several experimental and clinical studies have indicated that aberrations and deregulations of the UPS contribute to the pathogenesis of several neurodegenerative and myodegenerative disorders, including Alzheimer's disease,[22] Parkinson's disease[23] and Pick's disease,[24] Amyotrophic lateral sclerosis (ALS),[24] Huntington's disease,[23] Creutzfeldt–Jakob disease,[25] and motor neuron diseases, polyglutamine (PolyQ) diseases, Muscular dystrophies[26] and several rare forms of neurodegenerative diseases associated with dementia.[27] As part of the Ubiquitin-Proteasome System (UPS), the proteasome maintains cardiac protein homeostasis and thus plays a significant role in cardiac Ischemic injury,[28] ventricular hypertrophy[29] and Heart failure.[30] Additionally, evidence is accumulating that the UPS plays an essential role in malignant transformation. UPS proteolysis plays a major role in responses of cancer cells to stimulatory signals that are critical for the development of cancer. Accordingly, gene expression by degradation of transcription factors, such as p53, c-Jun, c-Fos, NF-κB, c-Myc, HIF-1α, MATα2, STAT3, sterol-regulated element-binding proteins and androgen receptors are all controlled by the UPS and thus involved in the development of various malignancies.[31] Moreover, the UPS regulates the degradation of tumor suppressor gene products such as adenomatous polyposis coli (APC) in colorectal cancer, retinoblastoma (Rb). and von Hippel-Lindau tumor suppressor (VHL), as well as a number of proto-oncogenes (Raf, Myc, Myb, Rel, Src, Mos, Abl). The UPS is also involved in the regulation of inflammatory responses. This activity is usually attributed to the role of proteasomes in the activation of NF-κB which further regulates the expression of pro inflammatory cytokines such as TNF-α, IL-β, IL-8, adhesion molecules (ICAM-1, VCAM-1, P-selectin) and prostaglandins and nitric oxide (NO).[20] Additionally, the UPS also plays a role in inflammatory responses as regulators of leukocyte proliferation, mainly through proteolysis of cyclines and the degradation of CDK inhibitors.[32] Lastly, autoimmune disease patients with SLE, Sjogren's syndrome and rheumatoid arthritis (RA) predominantly exhibit circulating proteasomes which can be applied as clinical biomarkers.[33] During the antigen processing for the major histocompatibility complex (MHC) class-I, the proteasome is the major degradation machinery that degrades the antigen and present the resulting peptides to cytotoxic T lymphocytes.[34][35] The immunoproteasome has been considered playing a critical role in improving the quality and quantity of generated class-I ligands.	https://www.wikidoc.org/index.php/PSMB10
72a5eddc62c99f328b9da2d876f20e77c6cb1f47	wikidoc	PSMD10	PSMD10 26S proteasome non-ATPase regulatory subunit 10 or gankyrin is an enzyme that in humans is encoded by the PSMD10 gene. Gankyrin is an oncoprotein that is a component of the 19S regulatory cap of the proteasome. Structurally, it contains a 33-amino acid ankyrin repeat that forms a series of alpha helices. It plays a key role in regulating the cell cycle via protein-protein interactions with the cyclin-dependent kinase CDK4. It also binds closely to the E3 ubiquitin ligase MDM2, which is a regulator of the degradation of p53 and retinoblastoma protein, both transcription factors involved in tumor suppression and found mutated in many cancers. Gankyrin also has an anti-apoptotic effect and is overexpressed in certain types of tumor cells such as hepatocellular carcinoma. # Function The 26S proteasome is a multicatalytic proteinase complex with a highly ordered structure composed of 2 complexes, a 20S core and a 19S regulator. The 20S core is composed of 4 rings of 28 non-identical subunits; 2 rings are composed of 7 alpha subunits and 2 rings are composed of 7 beta subunits. The 19S regulator is composed of a base, which contains 6 ATPase subunits and 2 non-ATPase subunits, and a lid, which contains up to 10 non-ATPase subunits. Proteasomes are distributed throughout eukaryotic cells at a high concentration and cleave peptides in an ATP/ubiquitin-dependent process in a non-lysosomal pathway. An essential function of a modified proteasome, the immunoproteasome, is the processing of class I MHC peptides. This gene encodes a non-ATPase subunit of the 19S regulator. Two transcripts encoding different isoforms have been described. Pseudogenes have been identified on chromosomes 3 and 20. # Clinical significance The Proteasome and its subunits are of clinical significance for at least two reasons: (1) a compromised complex assembly or a dysfunctional proteasome can be associated with the underlying pathophysiology of specific diseases, and (2) they can be exploited as drug targets for therapeutic interventions. More recently, more effort has been made to consider the proteasome for the development of novel diagnostic markers and strategies. An improved and comprehensive understanding of the pathophysiology of the proteasome should lead to clinical applications in the future. The proteasomes form a pivotal component for the Ubiquitin-Proteasome System (UPS) and corresponding cellular Protein Quality Control (PQC). Protein ubiquitination and subsequent proteolysis and degradation by the proteasome are important mechanisms in the regulation of the cell cycle, cell growth and differentiation, gene transcription, signal transduction and apoptosis. Subsequently, a compromised proteasome complex assembly and function lead to reduced proteolytic activities and the accumulation of damaged or misfolded protein species. Such protein accumulation may contribute to the pathogenesis and phenotypic characteristics in neurodegenerative diseases, cardiovascular diseases, inflammatory responses and autoimmune diseases, and systemic DNA damage responses leading to malignancies. Several experimental and clinical studies have indicated that aberrations and deregulations of the UPS contribute to the pathogenesis of several neurodegenerative and myodegenerative disorders, including Alzheimer's disease, Parkinson's disease and Pick's disease, Amyotrophic lateral sclerosis (ALS), Huntington's disease, Creutzfeldt–Jakob disease, and motor neuron diseases, polyglutamine (PolyQ) diseases, Muscular dystrophies and several rare forms of neurodegenerative diseases associated with dementia. As part of the Ubiquitin-Proteasome System (UPS), the proteasome maintains cardiac protein homeostasis and thus plays a significant role in cardiac Ischemic injury, ventricular hypertrophy and Heart failure. Additionally, evidence is accumulating that the UPS plays an essential role in malignant transformation. UPS proteolysis plays a major role in responses of cancer cells to stimulatory signals that are critical for the development of cancer. Accordingly, gene expression by degradation of transcription factors, such as p53, c-Jun, c-Fos, NF-κB, c-Myc, HIF-1α, MATα2, STAT3, sterol-regulated element-binding proteins and androgen receptors are all controlled by the UPS and thus involved in the development of various malignancies. Moreover, the UPS regulates the degradation of tumor suppressor gene products such as adenomatous polyposis coli (APC) in colorectal cancer, retinoblastoma (Rb). and von Hippel-Lindau tumor suppressor (VHL), as well as a number of proto-oncogenes (Raf, Myc, Myb, Rel, Src, Mos, Abl). The UPS is also involved in the regulation of inflammatory responses. This activity is usually attributed to the role of proteasomes in the activation of NF-κB which further regulates the expression of pro inflammatory cytokines such as TNF-α, IL-β, IL-8, adhesion molecules (ICAM-1, VCAM-1, P-selectin) and prostaglandins and nitric oxide (NO). Additionally, the UPS also plays a role in inflammatory responses as regulators of leukocyte proliferation, mainly through proteolysis of cyclines and the degradation of CDK inhibitors. Lastly, autoimmune disease patients with SLE, Sjogren's syndrome and rheumatoid arthritis (RA) predominantly exhibit circulating proteasomes which can be applied as clinical biomarkers. # Interactions PSMD10 has been shown to interact with: - Mdm2, - PAAF1, and - PSMC4.	PSMD10 26S proteasome non-ATPase regulatory subunit 10 or gankyrin is an enzyme that in humans is encoded by the PSMD10 gene.[1] Gankyrin is an oncoprotein that is a component of the 19S regulatory cap of the proteasome. Structurally, it contains a 33-amino acid ankyrin repeat that forms a series of alpha helices.[2] It plays a key role in regulating the cell cycle via protein-protein interactions with the cyclin-dependent kinase CDK4. It also binds closely to the E3 ubiquitin ligase MDM2, which is a regulator of the degradation of p53 and retinoblastoma protein, both transcription factors involved in tumor suppression and found mutated in many cancers.[3] Gankyrin also has an anti-apoptotic effect and is overexpressed in certain types of tumor cells such as hepatocellular carcinoma.[4] # Function The 26S proteasome is a multicatalytic proteinase complex with a highly ordered structure composed of 2 complexes, a 20S core and a 19S regulator. The 20S core is composed of 4 rings of 28 non-identical subunits; 2 rings are composed of 7 alpha subunits and 2 rings are composed of 7 beta subunits. The 19S regulator is composed of a base, which contains 6 ATPase subunits and 2 non-ATPase subunits, and a lid, which contains up to 10 non-ATPase subunits. Proteasomes are distributed throughout eukaryotic cells at a high concentration and cleave peptides in an ATP/ubiquitin-dependent process in a non-lysosomal pathway. An essential function of a modified proteasome, the immunoproteasome, is the processing of class I MHC peptides. This gene encodes a non-ATPase subunit of the 19S regulator. Two transcripts encoding different isoforms have been described. Pseudogenes have been identified on chromosomes 3 and 20.[5] # Clinical significance The Proteasome and its subunits are of clinical significance for at least two reasons: (1) a compromised complex assembly or a dysfunctional proteasome can be associated with the underlying pathophysiology of specific diseases, and (2) they can be exploited as drug targets for therapeutic interventions. More recently, more effort has been made to consider the proteasome for the development of novel diagnostic markers and strategies. An improved and comprehensive understanding of the pathophysiology of the proteasome should lead to clinical applications in the future. The proteasomes form a pivotal component for the Ubiquitin-Proteasome System (UPS) [6] and corresponding cellular Protein Quality Control (PQC). Protein ubiquitination and subsequent proteolysis and degradation by the proteasome are important mechanisms in the regulation of the cell cycle, cell growth and differentiation, gene transcription, signal transduction and apoptosis.[7] Subsequently, a compromised proteasome complex assembly and function lead to reduced proteolytic activities and the accumulation of damaged or misfolded protein species. Such protein accumulation may contribute to the pathogenesis and phenotypic characteristics in neurodegenerative diseases,[8][9] cardiovascular diseases,[10][11][12] inflammatory responses and autoimmune diseases,[13] and systemic DNA damage responses leading to malignancies.[14] Several experimental and clinical studies have indicated that aberrations and deregulations of the UPS contribute to the pathogenesis of several neurodegenerative and myodegenerative disorders, including Alzheimer's disease,[15] Parkinson's disease[16] and Pick's disease,[17] Amyotrophic lateral sclerosis (ALS),[17] Huntington's disease,[16] Creutzfeldt–Jakob disease,[18] and motor neuron diseases, polyglutamine (PolyQ) diseases, Muscular dystrophies[19] and several rare forms of neurodegenerative diseases associated with dementia.[20] As part of the Ubiquitin-Proteasome System (UPS), the proteasome maintains cardiac protein homeostasis and thus plays a significant role in cardiac Ischemic injury,[21] ventricular hypertrophy[22] and Heart failure.[23] Additionally, evidence is accumulating that the UPS plays an essential role in malignant transformation. UPS proteolysis plays a major role in responses of cancer cells to stimulatory signals that are critical for the development of cancer. Accordingly, gene expression by degradation of transcription factors, such as p53, c-Jun, c-Fos, NF-κB, c-Myc, HIF-1α, MATα2, STAT3, sterol-regulated element-binding proteins and androgen receptors are all controlled by the UPS and thus involved in the development of various malignancies.[24] Moreover, the UPS regulates the degradation of tumor suppressor gene products such as adenomatous polyposis coli (APC) in colorectal cancer, retinoblastoma (Rb). and von Hippel-Lindau tumor suppressor (VHL), as well as a number of proto-oncogenes (Raf, Myc, Myb, Rel, Src, Mos, Abl). The UPS is also involved in the regulation of inflammatory responses. This activity is usually attributed to the role of proteasomes in the activation of NF-κB which further regulates the expression of pro inflammatory cytokines such as TNF-α, IL-β, IL-8, adhesion molecules (ICAM-1, VCAM-1, P-selectin) and prostaglandins and nitric oxide (NO).[13] Additionally, the UPS also plays a role in inflammatory responses as regulators of leukocyte proliferation, mainly through proteolysis of cyclines and the degradation of CDK inhibitors.[25] Lastly, autoimmune disease patients with SLE, Sjogren's syndrome and rheumatoid arthritis (RA) predominantly exhibit circulating proteasomes which can be applied as clinical biomarkers.[26] # Interactions PSMD10 has been shown to interact with: - Mdm2,[27] - PAAF1,[28] and - PSMC4.[28][29][30]	https://www.wikidoc.org/index.php/PSMD10
d179fe656daf27ad8dd2ca00999ee68d95334941	wikidoc	PSMD11	PSMD11 26S proteasome non-ATPase regulatory subunit 11 is an enzyme that in humans is encoded by the PSMD11 gene. # Function The 26S proteasome is a multicatalytic proteinase complex with a highly ordered structure composed of 2 complexes, a 20S core and a 19S regulator. The 20S core is composed of 4 rings of 28 non-identical subunits; 2 rings are composed of 7 alpha subunits and 2 rings are composed of 7 beta subunits. The 19S regulator is composed of a base, which contains 6 ATPase subunits and 2 non-ATPase subunits, and a lid, which contains up to 10 non-ATPase subunits. Proteasomes are distributed throughout eukaryotic cells at a high concentration and cleave peptides in an ATP/ubiquitin-dependent process in a non-lysosomal pathway. An essential function of a modified proteasome, the immunoproteasome, is the processing of class I MHC peptides. This gene encodes a non-ATPase subunit of the 19S regulator. # Clinical significance The Proteasome and its subunits are of clinical significance for at least two reasons: (1) a compromised complex assembly or a dysfunctional proteasome can be associated with the underlying pathophysiology of specific diseases, and (2) they can be exploited as drug targets for therapeutic interventions. More recently, more effort has been made to consider the proteasome for the development of novel diagnostic markers and strategies. An improved and comprehensive understanding of the pathophysiology of the proteasome should lead to clinical applications in the future. The proteasomes form a pivotal component for the Ubiquitin-Proteasome System (UPS) and corresponding cellular Protein Quality Control (PQC). Protein ubiquitination and subsequent proteolysis and degradation by the proteasome are important mechanisms in the regulation of the cell cycle, cell growth and differentiation, gene transcription, signal transduction and apoptosis. Subsequently, a compromised proteasome complex assembly and function lead to reduced proteolytic activities and the accumulation of damaged or misfolded protein species. Such protein accumulation may contribute to the pathogenesis and phenotypic characteristics in neurodegenerative diseases, cardiovascular diseases, inflammatory responses and autoimmune diseases, and systemic DNA damage responses leading to malignancies. Several experimental and clinical studies have indicated that aberrations and deregulations of the UPS contribute to the pathogenesis of several neurodegenerative and myodegenerative disorders, including Alzheimer's disease, Parkinson's disease and Pick's disease, Amyotrophic lateral sclerosis (ALS), Huntington's disease, Creutzfeldt–Jakob disease, and motor neuron diseases, polyglutamine (PolyQ) diseases, Muscular dystrophies and several rare forms of neurodegenerative diseases associated with dementia. As part of the Ubiquitin-Proteasome System (UPS), the proteasome maintains cardiac protein homeostasis and thus plays a significant role in cardiac Ischemic injury, ventricular hypertrophy and Heart failure. Additionally, evidence is accumulating that the UPS plays an essential role in malignant transformation. UPS proteolysis plays a major role in responses of cancer cells to stimulatory signals that are critical for the development of cancer. Accordingly, gene expression by degradation of transcription factors, such as p53, c-Jun, c-Fos, NF-κB, c-Myc, HIF-1α, MATα2, STAT3, sterol-regulated element-binding proteins and androgen receptors are all controlled by the UPS and thus involved in the development of various malignancies. Moreover, the UPS regulates the degradation of tumor suppressor gene products such as adenomatous polyposis coli (APC) in colorectal cancer, retinoblastoma (Rb). and von Hippel-Lindau tumor suppressor (VHL), as well as a number of proto-oncogenes (Raf, Myc, Myb, Rel, Src, Mos, Abl). The UPS is also involved in the regulation of inflammatory responses. This activity is usually attributed to the role of proteasomes in the activation of NF-κB which further regulates the expression of pro inflammatory cytokines such as TNF-α, IL-β, IL-8, adhesion molecules (ICAM-1, VCAM-1, P-selectin) and prostaglandins and nitric oxide (NO). Additionally, the UPS also plays a role in inflammatory responses as regulators of leukocyte proliferation, mainly through proteolysis of cyclines and the degradation of CDK inhibitors. Lastly, autoimmune disease patients with SLE, Sjogren's syndrome and rheumatoid arthritis (RA) predominantly exhibit circulating proteasomes which can be applied as clinical biomarkers. Gene expression levels of the proteasomal subunits (PSMA1, PSMA5, PSMB4, PSMB5 and PSMD1) were investigated in 80 patients with neuroendocrine pulmonary tumors and compared to controls. The study reviled that PSMB4 mRNA was significantly associated with proliferative activity of neuroendocrine pulmonary tumors. However, a role of PSMA5 was also indicated in neuroendocrine pulmonary tumors. The PSMA5 protein has further been associated with the biosynthesis of conjugated linoleum acid (CLA) in mammary tissue.	PSMD11 26S proteasome non-ATPase regulatory subunit 11 is an enzyme that in humans is encoded by the PSMD11 gene.[1][2][3] # Function The 26S proteasome is a multicatalytic proteinase complex with a highly ordered structure composed of 2 complexes, a 20S core and a 19S regulator. The 20S core is composed of 4 rings of 28 non-identical subunits; 2 rings are composed of 7 alpha subunits and 2 rings are composed of 7 beta subunits. The 19S regulator is composed of a base, which contains 6 ATPase subunits and 2 non-ATPase subunits, and a lid, which contains up to 10 non-ATPase subunits. Proteasomes are distributed throughout eukaryotic cells at a high concentration and cleave peptides in an ATP/ubiquitin-dependent process in a non-lysosomal pathway. An essential function of a modified proteasome, the immunoproteasome, is the processing of class I MHC peptides. This gene encodes a non-ATPase subunit of the 19S regulator.[3] # Clinical significance The Proteasome and its subunits are of clinical significance for at least two reasons: (1) a compromised complex assembly or a dysfunctional proteasome can be associated with the underlying pathophysiology of specific diseases, and (2) they can be exploited as drug targets for therapeutic interventions. More recently, more effort has been made to consider the proteasome for the development of novel diagnostic markers and strategies. An improved and comprehensive understanding of the pathophysiology of the proteasome should lead to clinical applications in the future. The proteasomes form a pivotal component for the Ubiquitin-Proteasome System (UPS) [4] and corresponding cellular Protein Quality Control (PQC). Protein ubiquitination and subsequent proteolysis and degradation by the proteasome are important mechanisms in the regulation of the cell cycle, cell growth and differentiation, gene transcription, signal transduction and apoptosis.[5] Subsequently, a compromised proteasome complex assembly and function lead to reduced proteolytic activities and the accumulation of damaged or misfolded protein species. Such protein accumulation may contribute to the pathogenesis and phenotypic characteristics in neurodegenerative diseases,[6][7] cardiovascular diseases,[8][9][10] inflammatory responses and autoimmune diseases,[11] and systemic DNA damage responses leading to malignancies.[12] Several experimental and clinical studies have indicated that aberrations and deregulations of the UPS contribute to the pathogenesis of several neurodegenerative and myodegenerative disorders, including Alzheimer's disease,[13] Parkinson's disease[14] and Pick's disease,[15] Amyotrophic lateral sclerosis (ALS),[15] Huntington's disease,[14] Creutzfeldt–Jakob disease,[16] and motor neuron diseases, polyglutamine (PolyQ) diseases, Muscular dystrophies[17] and several rare forms of neurodegenerative diseases associated with dementia.[18] As part of the Ubiquitin-Proteasome System (UPS), the proteasome maintains cardiac protein homeostasis and thus plays a significant role in cardiac Ischemic injury,[19] ventricular hypertrophy[20] and Heart failure.[21] Additionally, evidence is accumulating that the UPS plays an essential role in malignant transformation. UPS proteolysis plays a major role in responses of cancer cells to stimulatory signals that are critical for the development of cancer. Accordingly, gene expression by degradation of transcription factors, such as p53, c-Jun, c-Fos, NF-κB, c-Myc, HIF-1α, MATα2, STAT3, sterol-regulated element-binding proteins and androgen receptors are all controlled by the UPS and thus involved in the development of various malignancies.[22] Moreover, the UPS regulates the degradation of tumor suppressor gene products such as adenomatous polyposis coli (APC) in colorectal cancer, retinoblastoma (Rb). and von Hippel-Lindau tumor suppressor (VHL), as well as a number of proto-oncogenes (Raf, Myc, Myb, Rel, Src, Mos, Abl). The UPS is also involved in the regulation of inflammatory responses. This activity is usually attributed to the role of proteasomes in the activation of NF-κB which further regulates the expression of pro inflammatory cytokines such as TNF-α, IL-β, IL-8, adhesion molecules (ICAM-1, VCAM-1, P-selectin) and prostaglandins and nitric oxide (NO).[11] Additionally, the UPS also plays a role in inflammatory responses as regulators of leukocyte proliferation, mainly through proteolysis of cyclines and the degradation of CDK inhibitors.[23] Lastly, autoimmune disease patients with SLE, Sjogren's syndrome and rheumatoid arthritis (RA) predominantly exhibit circulating proteasomes which can be applied as clinical biomarkers.[24] Gene expression levels of the proteasomal subunits (PSMA1, PSMA5, PSMB4, PSMB5 and PSMD1) were investigated in 80 patients with neuroendocrine pulmonary tumors and compared to controls. The study reviled that PSMB4 mRNA was significantly associated with proliferative activity of neuroendocrine pulmonary tumors.[25] However, a role of PSMA5 was also indicated in neuroendocrine pulmonary tumors. The PSMA5 protein has further been associated with the biosynthesis of conjugated linoleum acid (CLA) in mammary tissue.[26]	https://www.wikidoc.org/index.php/PSMD11
9971eda1e3151cc3d453925f0b30f8042666d120	wikidoc	PSMD12	PSMD12 26S proteasome non-ATPase regulatory subunit 12 is an enzyme that in humans is encoded by the PSMD12 gene. # Function The 26S proteasome is a multicatalytic proteinase complex with a highly ordered structure composed of 2 complexes, a 20S core and a 19S regulator. The 20S core is composed of 4 rings of 28 non-identical subunits; 2 rings are composed of 7 alpha subunits and 2 rings are composed of 7 beta subunits. The 19S regulator is composed of a base, which contains 6 ATPase subunits and 2 non-ATPase subunits, and a lid, which contains up to 10 non-ATPase subunits. Proteasomes are distributed throughout eukaryotic cells at a high concentration and cleave peptides in an ATP/ubiquitin-dependent process in a non-lysosomal pathway. An essential function of a modified proteasome, the immunoproteasome, is the processing of class I MHC peptides. This gene encodes a non-ATPase subunit of the 19S regulator. A pseudogene has been identified on chromosome 3. # Clinical significance The Proteasome and its subunits are of clinical significance for at least two reasons: (1) a compromised complex assembly or a dysfunctional proteasome can be associated with the underlying pathophysiology of specific diseases, and (2) they can be exploited as drug targets for therapeutic interventions. More recently, more effort has been made to consider the proteasome for the development of novel diagnostic markers and strategies. An improved and comprehensive understanding of the pathophysiology of the proteasome should lead to clinical applications in the future. The proteasomes form a pivotal component for the Ubiquitin-Proteasome System (UPS) and corresponding cellular Protein Quality Control (PQC). Protein ubiquitination and subsequent proteolysis and degradation by the proteasome are important mechanisms in the regulation of the cell cycle, cell growth and differentiation, gene transcription, signal transduction and apoptosis. Subsequently, a compromised proteasome complex assembly and function lead to reduced proteolytic activities and the accumulation of damaged or misfolded protein species. Such protein accumulation may contribute to the pathogenesis and phenotypic characteristics in neurodegenerative diseases, cardiovascular diseases, inflammatory responses and autoimmune diseases, and systemic DNA damage responses leading to malignancies. Several experimental and clinical studies have indicated that aberrations and deregulations of the UPS contribute to the pathogenesis of several neurodegenerative and myodegenerative disorders, including Alzheimer's disease, Parkinson's disease and Pick's disease, Amyotrophic lateral sclerosis (ALS), Huntington's disease, Creutzfeldt–Jakob disease, and motor neuron diseases, polyglutamine (PolyQ) diseases, Muscular dystrophies and several rare forms of neurodegenerative diseases associated with dementia. As part of the Ubiquitin-Proteasome System (UPS), the proteasome maintains cardiac protein homeostasis and thus plays a significant role in cardiac Ischemic injury, ventricular hypertrophy and Heart failure. Additionally, evidence is accumulating that the UPS plays an essential role in malignant transformation. UPS proteolysis plays a major role in responses of cancer cells to stimulatory signals that are critical for the development of cancer. Accordingly, gene expression by degradation of transcription factors, such as p53, c-Jun, c-Fos, NF-κB, c-Myc, HIF-1α, MATα2, STAT3, sterol-regulated element-binding proteins and androgen receptors are all controlled by the UPS and thus involved in the development of various malignancies. Moreover, the UPS regulates the degradation of tumor suppressor gene products such as adenomatous polyposis coli (APC) in colorectal cancer, retinoblastoma (Rb). and von Hippel-Lindau tumor suppressor (VHL), as well as a number of proto-oncogenes (Raf, Myc, Myb, Rel, Src, Mos, Abl). The UPS is also involved in the regulation of inflammatory responses. This activity is usually attributed to the role of proteasomes in the activation of NF-κB which further regulates the expression of pro inflammatory cytokines such as TNF-α, IL-β, IL-8, adhesion molecules (ICAM-1, VCAM-1, P-selectin) and prostaglandins and nitric oxide (NO). Additionally, the UPS also plays a role in inflammatory responses as regulators of leukocyte proliferation, mainly through proteolysis of cyclines and the degradation of CDK inhibitors. Lastly, autoimmune disease patients with SLE, Sjogren's syndrome and rheumatoid arthritis (RA) predominantly exhibit circulating proteasomes which can be applied as clinical biomarkers. Gene expression levels of the proteasomal subunits (PSMA1, PSMA5, PSMB4, PSMB5 and PSMD1) were investigated in 80 patients with neuroendocrine pulmonary tumors and compared to controls. The study reviled that PSMB4 mRNA was significantly associated with proliferative activity of neuroendocrine pulmonary tumors. However, a role of PSMA5 was also indicated in neuroendocrine pulmonary tumors. The PSMA5 protein has further been associated with the biosynthesis of conjugated linoleum acid (CLA) in mammary tissue.	PSMD12 26S proteasome non-ATPase regulatory subunit 12 is an enzyme that in humans is encoded by the PSMD12 gene.[1] # Function The 26S proteasome is a multicatalytic proteinase complex with a highly ordered structure composed of 2 complexes, a 20S core and a 19S regulator. The 20S core is composed of 4 rings of 28 non-identical subunits; 2 rings are composed of 7 alpha subunits and 2 rings are composed of 7 beta subunits. The 19S regulator is composed of a base, which contains 6 ATPase subunits and 2 non-ATPase subunits, and a lid, which contains up to 10 non-ATPase subunits. Proteasomes are distributed throughout eukaryotic cells at a high concentration and cleave peptides in an ATP/ubiquitin-dependent process in a non-lysosomal pathway. An essential function of a modified proteasome, the immunoproteasome, is the processing of class I MHC peptides. This gene encodes a non-ATPase subunit of the 19S regulator. A pseudogene has been identified on chromosome 3.[2] # Clinical significance The Proteasome and its subunits are of clinical significance for at least two reasons: (1) a compromised complex assembly or a dysfunctional proteasome can be associated with the underlying pathophysiology of specific diseases, and (2) they can be exploited as drug targets for therapeutic interventions. More recently, more effort has been made to consider the proteasome for the development of novel diagnostic markers and strategies. An improved and comprehensive understanding of the pathophysiology of the proteasome should lead to clinical applications in the future. The proteasomes form a pivotal component for the Ubiquitin-Proteasome System (UPS) [3] and corresponding cellular Protein Quality Control (PQC). Protein ubiquitination and subsequent proteolysis and degradation by the proteasome are important mechanisms in the regulation of the cell cycle, cell growth and differentiation, gene transcription, signal transduction and apoptosis.[4] Subsequently, a compromised proteasome complex assembly and function lead to reduced proteolytic activities and the accumulation of damaged or misfolded protein species. Such protein accumulation may contribute to the pathogenesis and phenotypic characteristics in neurodegenerative diseases,[5][6] cardiovascular diseases,[7][8][9] inflammatory responses and autoimmune diseases,[10] and systemic DNA damage responses leading to malignancies.[11] Several experimental and clinical studies have indicated that aberrations and deregulations of the UPS contribute to the pathogenesis of several neurodegenerative and myodegenerative disorders, including Alzheimer's disease,[12] Parkinson's disease[13] and Pick's disease,[14] Amyotrophic lateral sclerosis (ALS),[14] Huntington's disease,[13] Creutzfeldt–Jakob disease,[15] and motor neuron diseases, polyglutamine (PolyQ) diseases, Muscular dystrophies[16] and several rare forms of neurodegenerative diseases associated with dementia.[17] As part of the Ubiquitin-Proteasome System (UPS), the proteasome maintains cardiac protein homeostasis and thus plays a significant role in cardiac Ischemic injury,[18] ventricular hypertrophy[19] and Heart failure.[20] Additionally, evidence is accumulating that the UPS plays an essential role in malignant transformation. UPS proteolysis plays a major role in responses of cancer cells to stimulatory signals that are critical for the development of cancer. Accordingly, gene expression by degradation of transcription factors, such as p53, c-Jun, c-Fos, NF-κB, c-Myc, HIF-1α, MATα2, STAT3, sterol-regulated element-binding proteins and androgen receptors are all controlled by the UPS and thus involved in the development of various malignancies.[21] Moreover, the UPS regulates the degradation of tumor suppressor gene products such as adenomatous polyposis coli (APC) in colorectal cancer, retinoblastoma (Rb). and von Hippel-Lindau tumor suppressor (VHL), as well as a number of proto-oncogenes (Raf, Myc, Myb, Rel, Src, Mos, Abl). The UPS is also involved in the regulation of inflammatory responses. This activity is usually attributed to the role of proteasomes in the activation of NF-κB which further regulates the expression of pro inflammatory cytokines such as TNF-α, IL-β, IL-8, adhesion molecules (ICAM-1, VCAM-1, P-selectin) and prostaglandins and nitric oxide (NO).[10] Additionally, the UPS also plays a role in inflammatory responses as regulators of leukocyte proliferation, mainly through proteolysis of cyclines and the degradation of CDK inhibitors.[22] Lastly, autoimmune disease patients with SLE, Sjogren's syndrome and rheumatoid arthritis (RA) predominantly exhibit circulating proteasomes which can be applied as clinical biomarkers.[23] Gene expression levels of the proteasomal subunits (PSMA1, PSMA5, PSMB4, PSMB5 and PSMD1) were investigated in 80 patients with neuroendocrine pulmonary tumors and compared to controls. The study reviled that PSMB4 mRNA was significantly associated with proliferative activity of neuroendocrine pulmonary tumors.[24] However, a role of PSMA5 was also indicated in neuroendocrine pulmonary tumors. The PSMA5 protein has further been associated with the biosynthesis of conjugated linoleum acid (CLA) in mammary tissue.[25]	https://www.wikidoc.org/index.php/PSMD12
aecc05ead113b7a8a965ad6cb01b230827e27251	wikidoc	PSMD13	PSMD13 26S proteasome non-ATPase regulatory subunit 13 is an enzyme that in humans is encoded by the PSMD13 gene. # Function The 26S proteasome is a multicatalytic proteinase complex with a highly ordered structure composed of 2 complexes, a 20S core and a 19S regulator. The 20S core is composed of 4 rings of 28 non-identical subunits; 2 rings are composed of 7 alpha subunits and 2 rings are composed of 7 beta subunits. The 19S regulator is composed of a base, which contains 6 ATPase subunits and 2 non-ATPase subunits, and a lid, which contains up to 10 non-ATPase subunits. Proteasomes are distributed throughout eukaryotic cells at a high concentration and cleave peptides in an ATP/ubiquitin-dependent process in a non-lysosomal pathway. An essential function of a modified proteasome, the immunoproteasome, is the processing of class I MHC peptides. This gene encodes a non-ATPase subunit of the 19S regulator. Two transcripts encoding different isoforms have been described. # Clinical significance The Proteasome and its subunits are of clinical significance for at least two reasons: (1) a compromised complex assembly or a dysfunctional proteasome can be associated with the underlying pathophysiology of specific diseases, and (2) they can be exploited as drug targets for therapeutic interventions. More recently, more effort has been made to consider the proteasome for the development of novel diagnostic markers and strategies. An improved and comprehensive understanding of the pathophysiology of the proteasome should lead to clinical applications in the future. The proteasomes form a pivotal component for the Ubiquitin-Proteasome System (UPS) and corresponding cellular Protein Quality Control (PQC). Protein ubiquitination and subsequent proteolysis and degradation by the proteasome are important mechanisms in the regulation of the cell cycle, cell growth and differentiation, gene transcription, signal transduction and apoptosis. Subsequently, a compromised proteasome complex assembly and function lead to reduced proteolytic activities and the accumulation of damaged or misfolded protein species. Such protein accumulation may contribute to the pathogenesis and phenotypic characteristics in neurodegenerative diseases, cardiovascular diseases, inflammatory responses and autoimmune diseases, and systemic DNA damage responses leading to malignancies. Several experimental and clinical studies have indicated that aberrations and deregulations of the UPS contribute to the pathogenesis of several neurodegenerative and myodegenerative disorders, including Alzheimer's disease, Parkinson's disease and Pick's disease, Amyotrophic lateral sclerosis (ALS), Huntington's disease, Creutzfeldt–Jakob disease, and motor neuron diseases, polyglutamine (PolyQ) diseases, Muscular dystrophies and several rare forms of neurodegenerative diseases associated with dementia. As part of the Ubiquitin-Proteasome System (UPS), the proteasome maintains cardiac protein homeostasis and thus plays a significant role in cardiac Ischemic injury, ventricular hypertrophy and Heart failure. Additionally, evidence is accumulating that the UPS plays an essential role in malignant transformation. UPS proteolysis plays a major role in responses of cancer cells to stimulatory signals that are critical for the development of cancer. Accordingly, gene expression by degradation of transcription factors, such as p53, c-Jun, c-Fos, NF-κB, c-Myc, HIF-1α, MATα2, STAT3, sterol-regulated element-binding proteins and androgen receptors are all controlled by the UPS and thus involved in the development of various malignancies. Moreover, the UPS regulates the degradation of tumor suppressor gene products such as adenomatous polyposis coli (APC) in colorectal cancer, retinoblastoma (Rb). and von Hippel-Lindau tumor suppressor (VHL), as well as a number of proto-oncogenes (Raf, Myc, Myb, Rel, Src, Mos, Abl). The UPS is also involved in the regulation of inflammatory responses. This activity is usually attributed to the role of proteasomes in the activation of NF-κB which further regulates the expression of pro inflammatory cytokines such as TNF-α, IL-β, IL-8, adhesion molecules (ICAM-1, VCAM-1, P-selectin) and prostaglandins and nitric oxide (NO). Additionally, the UPS also plays a role in inflammatory responses as regulators of leukocyte proliferation, mainly through proteolysis of cyclines and the degradation of CDK inhibitors. Lastly, autoimmune disease patients with SLE, Sjogren's syndrome and rheumatoid arthritis (RA) predominantly exhibit circulating proteasomes which can be applied as clinical biomarkers. Gene expression levels of the proteasomal subunits (PSMA1, PSMA5, PSMB4, PSMB5 and PSMD1) were investigated in 80 patients with neuroendocrine pulmonary tumors and compared to controls. The study reviled that PSMB4 mRNA was significantly associated with proliferative activity of neuroendocrine pulmonary tumors. However, a role of PSMA5 was also indicated in neuroendocrine pulmonary tumors. The PSMA5 protein has further been associated with the biosynthesis of conjugated linoleum acid (CLA) in mammary tissue. # Interactions PSMD13 has been shown to interact with PSMC4 and PSMD6.	PSMD13 26S proteasome non-ATPase regulatory subunit 13 is an enzyme that in humans is encoded by the PSMD13 gene.[1][2] # Function The 26S proteasome is a multicatalytic proteinase complex with a highly ordered structure composed of 2 complexes, a 20S core and a 19S regulator. The 20S core is composed of 4 rings of 28 non-identical subunits; 2 rings are composed of 7 alpha subunits and 2 rings are composed of 7 beta subunits. The 19S regulator is composed of a base, which contains 6 ATPase subunits and 2 non-ATPase subunits, and a lid, which contains up to 10 non-ATPase subunits. Proteasomes are distributed throughout eukaryotic cells at a high concentration and cleave peptides in an ATP/ubiquitin-dependent process in a non-lysosomal pathway. An essential function of a modified proteasome, the immunoproteasome, is the processing of class I MHC peptides. This gene encodes a non-ATPase subunit of the 19S regulator. Two transcripts encoding different isoforms have been described.[3] # Clinical significance The Proteasome and its subunits are of clinical significance for at least two reasons: (1) a compromised complex assembly or a dysfunctional proteasome can be associated with the underlying pathophysiology of specific diseases, and (2) they can be exploited as drug targets for therapeutic interventions. More recently, more effort has been made to consider the proteasome for the development of novel diagnostic markers and strategies. An improved and comprehensive understanding of the pathophysiology of the proteasome should lead to clinical applications in the future. The proteasomes form a pivotal component for the Ubiquitin-Proteasome System (UPS) [4] and corresponding cellular Protein Quality Control (PQC). Protein ubiquitination and subsequent proteolysis and degradation by the proteasome are important mechanisms in the regulation of the cell cycle, cell growth and differentiation, gene transcription, signal transduction and apoptosis.[5] Subsequently, a compromised proteasome complex assembly and function lead to reduced proteolytic activities and the accumulation of damaged or misfolded protein species. Such protein accumulation may contribute to the pathogenesis and phenotypic characteristics in neurodegenerative diseases,[6][7] cardiovascular diseases,[8][9][10] inflammatory responses and autoimmune diseases,[11] and systemic DNA damage responses leading to malignancies.[12] Several experimental and clinical studies have indicated that aberrations and deregulations of the UPS contribute to the pathogenesis of several neurodegenerative and myodegenerative disorders, including Alzheimer's disease,[13] Parkinson's disease[14] and Pick's disease,[15] Amyotrophic lateral sclerosis (ALS),[15] Huntington's disease,[14] Creutzfeldt–Jakob disease,[16] and motor neuron diseases, polyglutamine (PolyQ) diseases, Muscular dystrophies[17] and several rare forms of neurodegenerative diseases associated with dementia.[18] As part of the Ubiquitin-Proteasome System (UPS), the proteasome maintains cardiac protein homeostasis and thus plays a significant role in cardiac Ischemic injury,[19] ventricular hypertrophy[20] and Heart failure.[21] Additionally, evidence is accumulating that the UPS plays an essential role in malignant transformation. UPS proteolysis plays a major role in responses of cancer cells to stimulatory signals that are critical for the development of cancer. Accordingly, gene expression by degradation of transcription factors, such as p53, c-Jun, c-Fos, NF-κB, c-Myc, HIF-1α, MATα2, STAT3, sterol-regulated element-binding proteins and androgen receptors are all controlled by the UPS and thus involved in the development of various malignancies.[22] Moreover, the UPS regulates the degradation of tumor suppressor gene products such as adenomatous polyposis coli (APC) in colorectal cancer, retinoblastoma (Rb). and von Hippel-Lindau tumor suppressor (VHL), as well as a number of proto-oncogenes (Raf, Myc, Myb, Rel, Src, Mos, Abl). The UPS is also involved in the regulation of inflammatory responses. This activity is usually attributed to the role of proteasomes in the activation of NF-κB which further regulates the expression of pro inflammatory cytokines such as TNF-α, IL-β, IL-8, adhesion molecules (ICAM-1, VCAM-1, P-selectin) and prostaglandins and nitric oxide (NO).[11] Additionally, the UPS also plays a role in inflammatory responses as regulators of leukocyte proliferation, mainly through proteolysis of cyclines and the degradation of CDK inhibitors.[23] Lastly, autoimmune disease patients with SLE, Sjogren's syndrome and rheumatoid arthritis (RA) predominantly exhibit circulating proteasomes which can be applied as clinical biomarkers.[24] Gene expression levels of the proteasomal subunits (PSMA1, PSMA5, PSMB4, PSMB5 and PSMD1) were investigated in 80 patients with neuroendocrine pulmonary tumors and compared to controls. The study reviled that PSMB4 mRNA was significantly associated with proliferative activity of neuroendocrine pulmonary tumors.[25] However, a role of PSMA5 was also indicated in neuroendocrine pulmonary tumors. The PSMA5 protein has further been associated with the biosynthesis of conjugated linoleum acid (CLA) in mammary tissue.[26] # Interactions PSMD13 has been shown to interact with PSMC4[27] and PSMD6.[27]	https://www.wikidoc.org/index.php/PSMD13
ac136555bc9792fc0c367d9ad6d3e08cdaaf7c7f	wikidoc	PSMD14	PSMD14 26S proteasome non-ATPase regulatory subunit 14, also known as 26S proteasome non-ATPase subunit Rpn11, is an enzyme that in humans is encoded by the PSMD14 gene. This protein is one of the 19 essential subunits of a complete assembled 19S proteasome complex. Nine subunits Rpn3, Rpn5, Rpn6, Rpn7, Rpn8, Rpn9, Rpn11, SEM1(Yeast analogue for human protein DSS1), and Rpn12 form the lid sub complex of 19S regulatory particle for proteasome complex. # Gene The gene PSMD14 encodes one of 26S proteasome non-ATPase subunit. The human gene PSMD14 has 12 Exons and locates at chromosome band 2q24.2. # Protein The human protein 26S proteasome non-ATPase regulatory subunit 14 is 34.6 kDa in size and composed of 310 amino acids. The calculated theoretical pI of this protein is 6.06. # Complex assembly 26S proteasome complex is usually consisted of a 20S core particle (CP, or 20S proteasome) and one or two 19S regulatory particles (RP, or 19S proteasome) on either one side or both side of the barrel-shaped 20S. The CP and RPs pertain distinct structural characteristics and biological functions. In brief, 20S sub complex presents three types proteolytic activities, including caspase-like, trypsin-like, and chymotrypsin-like activities. These proteolytic active sites located in the inner side of a chamber formed by 4 stacked rings of 20S subunits, preventing random protein-enzyme encounter and uncontrolled protein degradation. The 19S regulatory particles can recognize ubiquitin-labeled protein as degradation substrate, unfold the protein to linear, open the gate of 20S core particle, and guide the substate into the proteolytic chamber. To meet such functional complexity, 19S regulatory particle contains at least 18 constitutive subunits. These subunits can be categorized into two classes based on the ATP dependence of subunits, ATP-dependent subunits and ATP-independent subunits. According to the protein interaction and topological characteristics of this multisubunit complex, the 19S regulatory particle is composed of a base and a lid subcomplex. The base consists of a ring of six AAA ATPases (Subunit Rpt1-6, systematic nomenclature) and four non-ATPase subunits (Rpn1, Rpn2, Rpn10, and Rpn13).s The lid sub complex of 19S regulatory particle consisted of 9 subunits. The assembly of 19S lid is independent to the assembly process of 19S base. Two assembly modules, Rpn5-Rpn6-Rpn8-Rpn9-Rpn11 modules and Rpn3-Rpn7-SEM1 modules were identified during 19S lid assembly using yeast proteasome as a model complex. The subunit Rpn12 incorporated into 19S regulatory particle when 19S lid and base bind together. Among these lid subunits, protein Rpn11 presents the metalloproteases activity to hydrolyze the ubiquitin molecules from the poly-ubiquitin chain before protein substrates are unfolded and degraded. During substrate degradation, the 19S regulatory particles undergo a conformation switch that is characterized by a rearranged ATPase ring with uniform subunit interfaces. Notably, Rpn11 migrates from an occluded position to directly above the central pore, thus facilitating substrate deubiquitination concomitant with translocation. # Function As the degradation machinery that is responsible for ~70% of intracellular proteolysis, proteasome complex (26S proteasome) plays a critical roles in maintaining the homeostasis of cellular proteome. Accordingly, misfolded proteins and damaged protein need to be continuously removed to recycle amino acids for new synthesis; in parallel, some key regulatory proteins fulfill their biological functions via selective degradation; furthermore, proteins are digested into peptides for MHC class I antigen presentation. To meet such complicated demands in biological process via spatial and temporal proteolysis, protein substrates have to be recognized, recruited, and eventually hydrolyzed in a well controlled fashion. Thus, 19S regulatory particle pertains a series of important capabilities to address these functional challenges. To recognize protein as designated substrate, 19S complex has subunits that are capable to recognize proteins with a special degradative tag, the ubiquitinylation. It also have subunits that can bind with nucleotides (e.g., ATPs) in order to facilitate the association between 19S and 20S particles, as well as to cause confirmation changes of alpha subunit C-terminals that form the substate entrance of 20S complex. Protein Rpn11 presents the metalloproteases activity to hydrolyze the ubiquitin molecules from the poly-ubiquitin chain before protein substrates are unfolded and degraded # Clinical significance The Proteasome and its subunits are of clinical significance for at least two reasons: (1) a compromised complex assembly or a dysfunctional proteasome can be associated with the underlying pathophysiology of specific diseases, and (2) they can be exploited as drug targets for therapeutic interventions. More recently, more effort has been made to consider the proteasome for the development of novel diagnostic markers and strategies. An improved and comprehensive understanding of the pathophysiology of the proteasome should lead to clinical applications in the future. The proteasomes form a pivotal component for the Ubiquitin-Proteasome System (UPS) and corresponding cellular Protein Quality Control (PQC). Protein ubiquitination and subsequent proteolysis and degradation by the proteasome are important mechanisms in the regulation of the cell cycle, cell growth and differentiation, gene transcription, signal transduction and apoptosis. Subsequently, a compromised proteasome complex assembly and function lead to reduced proteolytic activities and the accumulation of damaged or misfolded protein species. Such protein accumulation may contribute to the pathogenesis and phenotypic characteristics in neurodegenerative diseases, cardiovascular diseases, inflammatory responses and autoimmune diseases, and systemic DNA damage responses leading to malignancies. Several experimental and clinical studies have indicated that aberrations and deregulations of the UPS contribute to the pathogenesis of several neurodegenerative and myodegenerative disorders, including Alzheimer's disease, Parkinson's disease and Pick's disease, Amyotrophic lateral sclerosis (ALS), Huntington's disease, Creutzfeldt–Jakob disease, and motor neuron diseases, polyglutamine (PolyQ) diseases, Muscular dystrophies and several rare forms of neurodegenerative diseases associated with dementia. As part of the Ubiquitin-Proteasome System (UPS), the proteasome maintains cardiac protein homeostasis and thus plays a significant role in cardiac Ischemic injury, ventricular hypertrophy and Heart failure. Additionally, evidence is accumulating that the UPS plays an essential role in malignant transformation. UPS proteolysis plays a major role in responses of cancer cells to stimulatory signals that are critical for the development of cancer. Accordingly, gene expression by degradation of transcription factors, such as p53, c-Jun, c-Fos, NF-κB, c-Myc, HIF-1α, MATα2, STAT3, sterol-regulated element-binding proteins and androgen receptors are all controlled by the UPS and thus involved in the development of various malignancies. Moreover, the UPS regulates the degradation of tumor suppressor gene products such as adenomatous polyposis coli (APC) in colorectal cancer, retinoblastoma (Rb). and von Hippel-Lindau tumor suppressor (VHL), as well as a number of proto-oncogenes (Raf, Myc, Myb, Rel, Src, Mos, Abl). The UPS is also involved in the regulation of inflammatory responses. This activity is usually attributed to the role of proteasomes in the activation of NF-κB which further regulates the expression of pro inflammatory cytokines such as TNF-α, IL-β, IL-8, adhesion molecules (ICAM-1, VCAM-1, P-selectin) and prostaglandins and nitric oxide (NO). Additionally, the UPS also plays a role in inflammatory responses as regulators of leukocyte proliferation, mainly through proteolysis of cyclines and the degradation of CDK inhibitors. Lastly, autoimmune disease patients with SLE, Sjogren's syndrome and rheumatoid arthritis (RA) predominantly exhibit circulating proteasomes which can be applied as clinical biomarkers.	PSMD14 26S proteasome non-ATPase regulatory subunit 14, also known as 26S proteasome non-ATPase subunit Rpn11, is an enzyme that in humans is encoded by the PSMD14 gene.[1][2] This protein is one of the 19 essential subunits of a complete assembled 19S proteasome complex.[3] Nine subunits Rpn3, Rpn5, Rpn6, Rpn7, Rpn8, Rpn9, Rpn11, SEM1(Yeast analogue for human protein DSS1), and Rpn12 form the lid sub complex of 19S regulatory particle for proteasome complex.[3] # Gene The gene PSMD14 encodes one of 26S proteasome non-ATPase subunit.[2] The human gene PSMD14 has 12 Exons and locates at chromosome band 2q24.2. # Protein The human protein 26S proteasome non-ATPase regulatory subunit 14 is 34.6 kDa in size and composed of 310 amino acids. The calculated theoretical pI of this protein is 6.06.[4] # Complex assembly 26S proteasome complex is usually consisted of a 20S core particle (CP, or 20S proteasome) and one or two 19S regulatory particles (RP, or 19S proteasome) on either one side or both side of the barrel-shaped 20S. The CP and RPs pertain distinct structural characteristics and biological functions. In brief, 20S sub complex presents three types proteolytic activities, including caspase-like, trypsin-like, and chymotrypsin-like activities. These proteolytic active sites located in the inner side of a chamber formed by 4 stacked rings of 20S subunits, preventing random protein-enzyme encounter and uncontrolled protein degradation. The 19S regulatory particles can recognize ubiquitin-labeled protein as degradation substrate, unfold the protein to linear, open the gate of 20S core particle, and guide the substate into the proteolytic chamber. To meet such functional complexity, 19S regulatory particle contains at least 18 constitutive subunits. These subunits can be categorized into two classes based on the ATP dependence of subunits, ATP-dependent subunits and ATP-independent subunits. According to the protein interaction and topological characteristics of this multisubunit complex, the 19S regulatory particle is composed of a base and a lid subcomplex. The base consists of a ring of six AAA ATPases (Subunit Rpt1-6, systematic nomenclature) and four non-ATPase subunits (Rpn1, Rpn2, Rpn10, and Rpn13).s The lid sub complex of 19S regulatory particle consisted of 9 subunits. The assembly of 19S lid is independent to the assembly process of 19S base. Two assembly modules, Rpn5-Rpn6-Rpn8-Rpn9-Rpn11 modules and Rpn3-Rpn7-SEM1 modules were identified during 19S lid assembly using yeast proteasome as a model complex.[5][6][7][8] The subunit Rpn12 incorporated into 19S regulatory particle when 19S lid and base bind together.[9] Among these lid subunits, protein Rpn11 presents the metalloproteases activity to hydrolyze the ubiquitin molecules from the poly-ubiquitin chain before protein substrates are unfolded and degraded.[10][11] During substrate degradation, the 19S regulatory particles undergo a conformation switch that is characterized by a rearranged ATPase ring with uniform subunit interfaces. Notably, Rpn11 migrates from an occluded position to directly above the central pore, thus facilitating substrate deubiquitination concomitant with translocation.[12] # Function As the degradation machinery that is responsible for ~70% of intracellular proteolysis,[13] proteasome complex (26S proteasome) plays a critical roles in maintaining the homeostasis of cellular proteome. Accordingly, misfolded proteins and damaged protein need to be continuously removed to recycle amino acids for new synthesis; in parallel, some key regulatory proteins fulfill their biological functions via selective degradation; furthermore, proteins are digested into peptides for MHC class I antigen presentation. To meet such complicated demands in biological process via spatial and temporal proteolysis, protein substrates have to be recognized, recruited, and eventually hydrolyzed in a well controlled fashion. Thus, 19S regulatory particle pertains a series of important capabilities to address these functional challenges. To recognize protein as designated substrate, 19S complex has subunits that are capable to recognize proteins with a special degradative tag, the ubiquitinylation. It also have subunits that can bind with nucleotides (e.g., ATPs) in order to facilitate the association between 19S and 20S particles, as well as to cause confirmation changes of alpha subunit C-terminals that form the substate entrance of 20S complex. Protein Rpn11 presents the metalloproteases activity to hydrolyze the ubiquitin molecules from the poly-ubiquitin chain before protein substrates are unfolded and degraded[10] # Clinical significance The Proteasome and its subunits are of clinical significance for at least two reasons: (1) a compromised complex assembly or a dysfunctional proteasome can be associated with the underlying pathophysiology of specific diseases, and (2) they can be exploited as drug targets for therapeutic interventions. More recently, more effort has been made to consider the proteasome for the development of novel diagnostic markers and strategies. An improved and comprehensive understanding of the pathophysiology of the proteasome should lead to clinical applications in the future. The proteasomes form a pivotal component for the Ubiquitin-Proteasome System (UPS) [14] and corresponding cellular Protein Quality Control (PQC). Protein ubiquitination and subsequent proteolysis and degradation by the proteasome are important mechanisms in the regulation of the cell cycle, cell growth and differentiation, gene transcription, signal transduction and apoptosis.[15] Subsequently, a compromised proteasome complex assembly and function lead to reduced proteolytic activities and the accumulation of damaged or misfolded protein species. Such protein accumulation may contribute to the pathogenesis and phenotypic characteristics in neurodegenerative diseases,[16][17] cardiovascular diseases,[18][19][20] inflammatory responses and autoimmune diseases,[21] and systemic DNA damage responses leading to malignancies.[22] Several experimental and clinical studies have indicated that aberrations and deregulations of the UPS contribute to the pathogenesis of several neurodegenerative and myodegenerative disorders, including Alzheimer's disease,[23] Parkinson's disease[24] and Pick's disease,[25] Amyotrophic lateral sclerosis (ALS),[25] Huntington's disease,[24] Creutzfeldt–Jakob disease,[26] and motor neuron diseases, polyglutamine (PolyQ) diseases, Muscular dystrophies[27] and several rare forms of neurodegenerative diseases associated with dementia.[28] As part of the Ubiquitin-Proteasome System (UPS), the proteasome maintains cardiac protein homeostasis and thus plays a significant role in cardiac Ischemic injury,[29] ventricular hypertrophy[30] and Heart failure.[31] Additionally, evidence is accumulating that the UPS plays an essential role in malignant transformation. UPS proteolysis plays a major role in responses of cancer cells to stimulatory signals that are critical for the development of cancer. Accordingly, gene expression by degradation of transcription factors, such as p53, c-Jun, c-Fos, NF-κB, c-Myc, HIF-1α, MATα2, STAT3, sterol-regulated element-binding proteins and androgen receptors are all controlled by the UPS and thus involved in the development of various malignancies.[32] Moreover, the UPS regulates the degradation of tumor suppressor gene products such as adenomatous polyposis coli (APC) in colorectal cancer, retinoblastoma (Rb). and von Hippel-Lindau tumor suppressor (VHL), as well as a number of proto-oncogenes (Raf, Myc, Myb, Rel, Src, Mos, Abl). The UPS is also involved in the regulation of inflammatory responses. This activity is usually attributed to the role of proteasomes in the activation of NF-κB which further regulates the expression of pro inflammatory cytokines such as TNF-α, IL-β, IL-8, adhesion molecules (ICAM-1, VCAM-1, P-selectin) and prostaglandins and nitric oxide (NO).[21] Additionally, the UPS also plays a role in inflammatory responses as regulators of leukocyte proliferation, mainly through proteolysis of cyclines and the degradation of CDK inhibitors.[33] Lastly, autoimmune disease patients with SLE, Sjogren's syndrome and rheumatoid arthritis (RA) predominantly exhibit circulating proteasomes which can be applied as clinical biomarkers.[34]	https://www.wikidoc.org/index.php/PSMD14
9e8e349c30009d2adeb154a1a03c01a0d7564ee5	wikidoc	PTPN11	PTPN11 Tyrosine-protein phosphatase non-receptor type 11 (PTPN11) also known as protein-tyrosine phosphatase 1D (PTP-1D), SHP-2, or protein-tyrosine phosphatase 2C (PTP-2C) is an enzyme that in humans is encoded by the PTPN11 gene. PTPN11 is a protein tyrosine phosphatase (PTP) Shp2. PTPN11 is a member of the protein tyrosine phosphatase (PTP) family. PTPs are known to be signaling molecules that regulate a variety of cellular processes including cell growth, differentiation, mitotic cycle, and oncogenic transformation. This PTP contains two tandem Src homology-2 domains, which function as phospho-tyrosine binding domains and mediate the interaction of this PTP with its substrates. This PTP is widely expressed in most tissues and plays a regulatory role in various cell signaling events that are important for a diversity of cell functions, such as mitogenic activation, metabolic control, transcription regulation, and cell migration. Mutations in this gene are a cause of Noonan syndrome as well as acute myeloid leukemia. # Structure and function This phosphatase, along with its paralogue, Shp1, possesses a domain structure that consists of two tandem SH2 domains in its N-terminus followed by a protein tyrosine phosphatase (PTP) domain. In the inactive state, the N-terminal SH2 domain binds the PTP domain and blocks access of potential substrates to the active site. Thus, Shp2 is auto-inhibited. Upon binding to target phospho-tyrosyl residues, the N-terminal SH2 domain is released from the PTP domain, catalytically activating the enzyme by relieving this auto-inhibition. # Genetic diseases associated with PTPN11 Missense mutations in the PTPN11 locus are associated with both Noonan syndrome and Leopard syndrome. It has also been associated with Metachondromatosis. ## Noonan syndrome In the case of Noonan syndrome, mutations are broadly distributed throughout the coding region of the gene but all appear to result in hyper-activated, or unregulated mutant forms of the protein. Most of these mutations disrupt the binding interface between the N-SH2 domain and catalytic core necessary for the enzyme to maintain its auto-inhibited conformation. ## Leopard syndrome The mutations that cause Leopard syndrome are restricted regions affecting the catalytic core of the enzyme producing catalytically impaired Shp2 variants. It is currently unclear how mutations that give rise to mutant variants of Shp2 with biochemically opposite characteristics result in similar human genetic syndromes. # Cancer associated with PTPN11 Patients with a subset of Noonan syndrome PTPN11 mutations also have a higher prevalence of juvenile myelomonocytic leukemias (JMML). Activating Shp2 mutations have also been detected in neuroblastoma, melanoma, acute myeloid leukemia, breast cancer, lung cancer, colorectal cancer. Recently, a relatively high prevalence of PTPN11 mutations (24%) were detected by next-generation sequencing in a cohort of NPM1-mutated acute myeloid leukemia patients, although the prognostic significance of such associations has not been clarified. These data suggests that Shp2 may be a proto-oncogene. However, it has been reported that PTPN11/Shp2 can act as either tumor promoter or suppressor. In aged mouse model, hepatocyte-specific deletion of PTPN11/Shp2 promotes inflammatory signaling through the STAT3 pathway and hepatic inflammation/necrosis, resulting in regenerative hyperplasia and spontaneous development of tumors. Decreased PTPN11/Shp2 expression was detected in a subfraction of human hepatocellular carcinoma (HCC) specimens. The bacterium Helicobacter pylori has been associated with gastric cancer, and this is thought to be mediated in part by the interaction of its virulence factor CagA with SHP2. # Interactions PTPN11 has been shown to interact with - CagA, - Cbl gene, - CD117, - CD31, - CEACAM1, - Epidermal growth factor receptor, - Erk - FRS2, - GAB1, - GAB2, - Glycoprotein 130, - Grb2, - Growth hormone receptor, - HoxA10, - Insulin receptor, - Insulin-like growth factor 1 receptor, - IRS1, - Janus kinase 1, - Janus kinase 2, - LAIR1, - LRP1, - PDGFRB, - PI3K → Akt - PLCG2, - PTK2B, - Ras - SLAMF1, - SOCS3, - SOS1, - STAT3, - STAT5A, and - STAT5B. ## H Pylori CagA virulence factor CagA is a protein and virulence factor inserted by Helicobacter pylori into gastric epithelia. Once activated by SRC phosphorylation, CagA binds to SHP2, allosterically activating it. This leads to morphological changes, abnormal mitogenic signals and sustained activity can result in apoptosis of the host cell. Epidemiological studies have shown roles of cagA- positive H. pylori in the development of atrophic gastritis, peptic ulcer disease and gastric carcinoma.	PTPN11 Tyrosine-protein phosphatase non-receptor type 11 (PTPN11) also known as protein-tyrosine phosphatase 1D (PTP-1D), SHP-2, or protein-tyrosine phosphatase 2C (PTP-2C) is an enzyme that in humans is encoded by the PTPN11 gene. PTPN11 is a protein tyrosine phosphatase (PTP) Shp2.[1][2] PTPN11 is a member of the protein tyrosine phosphatase (PTP) family. PTPs are known to be signaling molecules that regulate a variety of cellular processes including cell growth, differentiation, mitotic cycle, and oncogenic transformation. This PTP contains two tandem Src homology-2 domains, which function as phospho-tyrosine binding domains and mediate the interaction of this PTP with its substrates. This PTP is widely expressed in most tissues and plays a regulatory role in various cell signaling events that are important for a diversity of cell functions, such as mitogenic activation, metabolic control, transcription regulation, and cell migration. Mutations in this gene are a cause of Noonan syndrome as well as acute myeloid leukemia.[3] # Structure and function This phosphatase, along with its paralogue, Shp1, possesses a domain structure that consists of two tandem SH2 domains in its N-terminus followed by a protein tyrosine phosphatase (PTP) domain. In the inactive state, the N-terminal SH2 domain binds the PTP domain and blocks access of potential substrates to the active site. Thus, Shp2 is auto-inhibited. Upon binding to target phospho-tyrosyl residues, the N-terminal SH2 domain is released from the PTP domain, catalytically activating the enzyme by relieving this auto-inhibition. # Genetic diseases associated with PTPN11 Missense mutations in the PTPN11 locus are associated with both Noonan syndrome and Leopard syndrome. It has also been associated with Metachondromatosis.[4] ## Noonan syndrome In the case of Noonan syndrome, mutations are broadly distributed throughout the coding region of the gene but all appear to result in hyper-activated, or unregulated mutant forms of the protein. Most of these mutations disrupt the binding interface between the N-SH2 domain and catalytic core necessary for the enzyme to maintain its auto-inhibited conformation.[5] ## Leopard syndrome The mutations that cause Leopard syndrome are restricted regions affecting the catalytic core of the enzyme producing catalytically impaired Shp2 variants.[6] It is currently unclear how mutations that give rise to mutant variants of Shp2 with biochemically opposite characteristics result in similar human genetic syndromes. # Cancer associated with PTPN11 Patients with a subset of Noonan syndrome PTPN11 mutations also have a higher prevalence of juvenile myelomonocytic leukemias (JMML). Activating Shp2 mutations have also been detected in neuroblastoma, melanoma, acute myeloid leukemia, breast cancer, lung cancer, colorectal cancer.[7] Recently, a relatively high prevalence of PTPN11 mutations (24%) were detected by next-generation sequencing in a cohort of NPM1-mutated acute myeloid leukemia patients,[8] although the prognostic significance of such associations has not been clarified. These data suggests that Shp2 may be a proto-oncogene. However, it has been reported that PTPN11/Shp2 can act as either tumor promoter or suppressor.[9] In aged mouse model, hepatocyte-specific deletion of PTPN11/Shp2 promotes inflammatory signaling through the STAT3 pathway and hepatic inflammation/necrosis, resulting in regenerative hyperplasia and spontaneous development of tumors. Decreased PTPN11/Shp2 expression was detected in a subfraction of human hepatocellular carcinoma (HCC) specimens.[9] The bacterium Helicobacter pylori has been associated with gastric cancer, and this is thought to be mediated in part by the interaction of its virulence factor CagA with SHP2.[10] # Interactions PTPN11 has been shown to interact with - CagA,[10] - Cbl gene,[11] - CD117,[12][13] - CD31,[14][15][16][17] - CEACAM1,[18] - Epidermal growth factor receptor,[19][20] - Erk [21][22] - FRS2,[23][24][25] - GAB1,[26][27] - GAB2,[28][29][30][31] - Glycoprotein 130,[32][33][34] - Grb2,[25][35][36][37][38][39][40][41][42] - Growth hormone receptor,[43][44] - HoxA10,[45] - Insulin receptor,[46][47] - Insulin-like growth factor 1 receptor,[48][49] - IRS1,[50][51] - Janus kinase 1,[32][35] - Janus kinase 2,[35][52][53] - LAIR1,[54][55] - LRP1,[56] - PDGFRB,[57][58] - PI3K → Akt [21] - PLCG2,[28] - PTK2B,[59] - Ras[21][22] - SLAMF1,[60][61] - SOCS3,[32] - SOS1,[25][62] - STAT3,[9] - STAT5A,[63][64] and - STAT5B.[63] ## H Pylori CagA virulence factor CagA is a protein and virulence factor inserted by Helicobacter pylori into gastric epithelia. Once activated by SRC phosphorylation, CagA binds to SHP2, allosterically activating it. This leads to morphological changes, abnormal mitogenic signals and sustained activity can result in apoptosis of the host cell. Epidemiological studies have shown roles of cagA- positive H. pylori in the development of atrophic gastritis, peptic ulcer disease and gastric carcinoma.[65]	https://www.wikidoc.org/index.php/PTPN11
262c0e106fbedbca939e9270f734f0b48d67e0c5	wikidoc	PTPN12	PTPN12 Tyrosine-protein phosphatase non-receptor type 12 is an enzyme that in humans is encoded by the PTPN12 gene. The protein encoded by this gene is a member of the protein tyrosine phosphatase (PTP) family. PTPs are known to be signaling molecules that regulate a variety of cellular processes including cell growth, differentiation, mitotic cycle, and oncogenic transformation. This PTP contains a C-terminal PEST motif, which serves as a protein–protein interaction domain, and may be related to protein intracellular half-life. This PTP was found to bind and dephosphorylate the product of oncogene c-ABL, thus may play a role in oncogenesis. This PTP was shown to interact with, and dephosphorylate, various of cytoskeleton and cell adhesion molecules, such as p130 (Cas), CAKbeta/PTK2B, PSTPIP1, and paxillin, which suggested its regulatory roles in controlling cell shape and mobility. # Interactions PTPN12 has been shown to interact with BCAR1, Grb2, PSTPIP1, TGFB1I1, Paxillin and SHC1.	PTPN12 Tyrosine-protein phosphatase non-receptor type 12 is an enzyme that in humans is encoded by the PTPN12 gene.[1][2] The protein encoded by this gene is a member of the protein tyrosine phosphatase (PTP) family. PTPs are known to be signaling molecules that regulate a variety of cellular processes including cell growth, differentiation, mitotic cycle, and oncogenic transformation. This PTP contains a C-terminal PEST motif, which serves as a protein–protein interaction domain, and may be related to protein intracellular half-life. This PTP was found to bind and dephosphorylate the product of oncogene c-ABL, thus may play a role in oncogenesis. This PTP was shown to interact with, and dephosphorylate, various of cytoskeleton and cell adhesion molecules, such as p130 (Cas), CAKbeta/PTK2B, PSTPIP1, and paxillin, which suggested its regulatory roles in controlling cell shape and mobility.[2] # Interactions PTPN12 has been shown to interact with BCAR1,[3][4][5][6] Grb2,[7] PSTPIP1,[8] TGFB1I1,[9] Paxillin[10][11][12] and SHC1.[13][14]	https://www.wikidoc.org/index.php/PTPN12
681c5f8069b33abf6749b642a676fc7ec6f38552	wikidoc	PTPN22	PTPN22 Protein tyrosine phosphatase, non-receptor type 22 (lymphoid), also known as PTPN22, is a protein that in humans is encoded by the PTPN22 gene. This gene can be expressed in different forms. PTPN22 affects the responsiveness of T and B cell receptors, and mutations are associated with increases or decreases in risks of autoimmune diseases. # Molecular biology The gene is located on the short arm of Chromosome 1 near the centromere (1p13.2) on the Crick (minus) strand. It is 57,898 bases in length and encodes a protein of 807 amino acids (molecular weight 91,705 Da). There are 24 exons in the gene and 21 transcript variants encoding 10 distinct proteins are known. The proteins are located in the cytoplasm. # Function This gene encodes a protein tyrosine phosphatase which is expressed primarily in lymphoid tissues. This enzyme is involved in several signalling pathways associated with the immune response. Based on models of the murine phosphatase, structural identification, and human genetics the phosphatase forms complexes with C-src tyrosine kinase (Csk), associated with the control of Src family members. The mutation Arg620Trp disrupts binding to Csk, alters the responsiveness of T and B cell receptors, and is associated with autoimmune diseases. There are other suggestions that the phosphatase regulates CBL function in the T cell receptor signaling pathway. Other interactions are likely. # Disease association The common 1858T (rs2476601) Arg620Trp nonsynonymous single nucleotide polymorphism located in the PTPN22 gene has been associated with autoimmune disorders, including an increased risk of Type 1 Diabetes, rheumatoid arthritis, Systemic Lupus Erythematosus, Vitiligo and Graves' disease, but a decreased risk of Crohn's disease. A recent study suggests that the mutation does not, on a population basis, reduce life span. The mutation may be conserved in human evolution because it may provide a hyper-immune response to infectious disease. Mutations in PTPN22 are over-represented in breast cancer.	PTPN22 Protein tyrosine phosphatase, non-receptor type 22 (lymphoid), also known as PTPN22, is a protein that in humans is encoded by the PTPN22 gene.[1][2][3] This gene can be expressed in different forms. PTPN22 affects the responsiveness of T and B cell receptors, and mutations are associated with increases or decreases in risks of autoimmune diseases. # Molecular biology The gene is located on the short arm of Chromosome 1 near the centromere (1p13.2) on the Crick (minus) strand. It is 57,898 bases in length and encodes a protein of 807 amino acids (molecular weight 91,705 Da). There are 24 exons in the gene and 21 transcript variants encoding 10 distinct proteins are known. The proteins are located in the cytoplasm.[citation needed] # Function This gene encodes a protein tyrosine phosphatase which is expressed primarily in lymphoid tissues. This enzyme is involved in several signalling pathways associated with the immune response. Based on models of the murine phosphatase,[4][5] structural identification,[6] and human genetics[7] the phosphatase forms complexes with C-src tyrosine kinase (Csk), associated with the control of Src family members. The mutation Arg620Trp disrupts binding to Csk, alters the responsiveness of T and B cell receptors, and is associated with autoimmune diseases. There are other suggestions that the phosphatase regulates CBL function in the T cell receptor signaling pathway.[1] Other interactions are likely. # Disease association The common 1858T (rs2476601) Arg620Trp nonsynonymous single nucleotide polymorphism located in the PTPN22 gene has been associated with autoimmune disorders, including an increased risk of Type 1 Diabetes, rheumatoid arthritis, Systemic Lupus Erythematosus, Vitiligo and Graves' disease, but a decreased risk of Crohn's disease.[8][9] A recent study suggests that the mutation does not, on a population basis, reduce life span.[10] The mutation may be conserved in human evolution because it may provide a hyper-immune response to infectious disease.[11] Mutations in PTPN22 are over-represented in breast cancer.[12]	https://www.wikidoc.org/index.php/PTPN22
880db997151727f6e2d086b56e49b46b6fb69000	wikidoc	PTPRN2	PTPRN2 Receptor-type tyrosine-protein phosphatase N2 (R-PTP-N2) also known as islet cell autoantigen-related protein (ICAAR) and phogrin is an enzyme that in humans is encoded by the PTPRN2 gene. PTPRN and PTPRN2 (this gene) are both found to be major autoantigens associated with insulin-dependent diabetes mellitus. # Function Due to a close similarity in the gene sequences, the protein encoded by this gene has traditionally been considered a member of the protein tyrosine phosphatase (PTP) family. PTPs are known to be signaling molecules that regulate a variety of cellular processes including cell growth, differentiation, mitotic cycle, and oncogenic transformation. However, recent research has shown that the PTPRN2 mouse homolog, known as phogrin, dephosphorylates the lipid phosphatidylinositol rather than tyrosine. Specifically, phogrin was shown to act upon phosphatidylinositol 3-phosphate and Phosphatidylinositol 4,5-diphosphate, whereas it has never been observed acting upon tyrosine. PTPRN2 should, therefore, be more accurately considered a PIPase rather than a PTPase. Phosphorylated forms of phosphatidylinositol (PI) are called phosphoinositides and play important roles in lipid signaling, cell signaling and membrane trafficking. The protein produced by PTPRN2 possesses an extracellular region, a single transmembrane region, and a single intracellular catalytic domain, and thus represents a receptor-type PTP. The catalytic domain of this PTP is most closely related to PTPRN, also known as IA-2. # Gene Three alternatively spliced transcript variants of this gene, which encode distinct proteins, have been reported. # Interactions PTPRN2 has been shown to interact with: CKAP5, SPTBN4, and UBQLN4. # Clinical significance R-PTP-N2 functions as an autoantigen in diabetes mellitus type 1.	PTPRN2 Receptor-type tyrosine-protein phosphatase N2 (R-PTP-N2) also known as islet cell autoantigen-related protein (ICAAR) and phogrin is an enzyme that in humans is encoded by the PTPRN2 gene.[1][2][3] PTPRN and PTPRN2 (this gene) are both found to be major autoantigens associated with insulin-dependent diabetes mellitus.[3] # Function Due to a close similarity in the gene sequences, the protein encoded by this gene has traditionally been considered a member of the protein tyrosine phosphatase (PTP) family. PTPs are known to be signaling molecules that regulate a variety of cellular processes including cell growth, differentiation, mitotic cycle, and oncogenic transformation. However, recent research has shown that the PTPRN2 mouse homolog, known as phogrin, dephosphorylates the lipid phosphatidylinositol rather than tyrosine. Specifically, phogrin was shown to act upon phosphatidylinositol 3-phosphate and Phosphatidylinositol 4,5-diphosphate, whereas it has never been observed acting upon tyrosine.[4] PTPRN2 should, therefore, be more accurately considered a PIPase rather than a PTPase. Phosphorylated forms of phosphatidylinositol (PI) are called phosphoinositides and play important roles in lipid signaling, cell signaling and membrane trafficking. The protein produced by PTPRN2 possesses an extracellular region, a single transmembrane region, and a single intracellular catalytic domain, and thus represents a receptor-type PTP. The catalytic domain of this PTP is most closely related to PTPRN, also known as IA-2.[3] # Gene Three alternatively spliced transcript variants of this gene, which encode distinct proteins, have been reported.[3] # Interactions PTPRN2 has been shown to interact with: CKAP5,[5] SPTBN4,[6] and UBQLN4.[7] # Clinical significance R-PTP-N2 functions as an autoantigen in diabetes mellitus type 1.[8][9]	https://www.wikidoc.org/index.php/PTPRN2
86c89d094aebb3a4ca4efc8d812c7ec0bbdd6456	wikidoc	PTPRZ1	PTPRZ1 Receptor-type tyrosine-protein phosphatase zeta also known as phosphacan is an enzyme that in humans is encoded by the PTPRZ1 gene. # Function This gene is a member of the receptor tyrosine phosphatase family and encodes a single-pass type I membrane protein with two cytoplasmic tyrosine-protein phosphatase domains, an alpha-carbonic anhydrase domain and a fibronectin type III domain. Alternative splice variants that encode different protein isoforms have been described but their full-length nature has not been determined. # Clinical significance Expression of this gene is induced in gastric cancer cells, in the remyelinating oligodendrocytes of multiple sclerosis lesions, and in human embryonic kidney cells under hypoxic conditions. Both the protein and transcript are overexpressed in glioblastoma cells, promoting their haptotactic migration.	PTPRZ1 Receptor-type tyrosine-protein phosphatase zeta also known as phosphacan is an enzyme that in humans is encoded by the PTPRZ1 gene.[1][2][3] # Function This gene is a member of the receptor tyrosine phosphatase family and encodes a single-pass type I membrane protein with two cytoplasmic tyrosine-protein phosphatase domains, an alpha-carbonic anhydrase domain and a fibronectin type III domain. Alternative splice variants that encode different protein isoforms have been described but their full-length nature has not been determined.[3] # Clinical significance Expression of this gene is induced in gastric cancer cells, in the remyelinating oligodendrocytes of multiple sclerosis lesions, and in human embryonic kidney cells under hypoxic conditions. Both the protein and transcript are overexpressed in glioblastoma cells, promoting their haptotactic migration.[3]	https://www.wikidoc.org/index.php/PTPRZ1
ea95a6899518071e78fee75ec44264912a4f8fbb	wikidoc	PYCARD	PYCARD PYCARD, often referred to as ASC (Apoptosis-associated speck-like protein containing a CARD), is a protein that in humans is encoded by the PYCARD gene. It is localized mainly in the nucleus of monocytes and macrophages. In case of pathogen infection, however, it relocalizes rapidly to the cytoplasm, perinuclear space, endoplasmic reticulum and mitochondria and it is a key adaptor protein in activation of the inflammasome . NMR structure of full-length ASC: PDB ID 2KN6 # Function This gene encodes an adaptor protein that is composed of two protein–protein interaction domains: a N-terminal PYRIN-PAAD-DAPIN domain (PYD) and a C-terminal caspase-recruitment domain (CARD). The PYD and CARD domains are members of the six-helix bundle death domain-fold superfamily that mediates assembly of large signaling complexes in the inflammatory and apoptotic signaling pathways via the activation of caspase. In normal cells, this protein is localized to the cytoplasm; however, in cells undergoing apoptosis, it forms ball-like aggregates near the nuclear periphery. PYCARD can occur in four different isoforms. Isoform 1, often referred to as canonical PYCARD, and isoform 2 are the activatory isoforms. They co-localize with nucleotide oligomerization domain-like receptors (NLRs) and caspase-1. Unlike isoform 1, isoform 2 is involved in direct IL-1β processing regulation. Isoform 3 is an inhibitory isoform, so that it only co-localizes with caspase-1, but not with NLRs. Isoform 4 is not able to act as an adaptor protein in NLR signalling and its role remains elusive. # Interactions PYCARD has been shown to interact with MEFV.	PYCARD PYCARD, often referred to as ASC (Apoptosis-associated speck-like protein containing a CARD), is a protein that in humans is encoded by the PYCARD gene.[1] It is localized mainly in the nucleus of monocytes and macrophages. In case of pathogen infection, however, it relocalizes rapidly to the cytoplasm, perinuclear space, endoplasmic reticulum and mitochondria and it is a key adaptor protein in activation of the inflammasome [2]. NMR structure of full-length ASC: PDB ID 2KN6 [2][3] # Function This gene encodes an adaptor protein that is composed of two protein–protein interaction domains: a N-terminal PYRIN-PAAD-DAPIN domain (PYD) and a C-terminal caspase-recruitment domain (CARD). The PYD and CARD domains are members of the six-helix bundle death domain-fold superfamily that mediates assembly of large signaling complexes in the inflammatory and apoptotic signaling pathways via the activation of caspase. In normal cells, this protein is localized to the cytoplasm; however, in cells undergoing apoptosis, it forms ball-like aggregates near the nuclear periphery. PYCARD can occur in four different isoforms. Isoform 1, often referred to as canonical PYCARD, and isoform 2 are the activatory isoforms. They co-localize with nucleotide oligomerization domain-like receptors (NLRs) and caspase-1. Unlike isoform 1, isoform 2 is involved in direct IL-1β processing regulation. Isoform 3 is an inhibitory isoform, so that it only co-localizes with caspase-1, but not with NLRs. Isoform 4 is not able to act as an adaptor protein in NLR signalling and its role remains elusive[2]. # Interactions PYCARD has been shown to interact with MEFV.[4]	https://www.wikidoc.org/index.php/PYCARD
9396a0f688defc71cd6feb532667e3add862ceff	wikidoc	Palate	Palate # Overview The palate (Template:IPAEng) is the roof of the mouth in humans and vertebrate animals. It separates the oral cavity from the nasal cavity. The palate is divided into two parts, the anterior bony hard palate, and the posterior fleshy soft palate or velum. The maxillary nerve branch of the trigeminal nerve (V) supplies sensory innervation to the palate. # Etymology The name is middle English and is probably derived from the Latin palatum or the Old French palat. # Function When functioning in conjunction with other parts of the mouth the palate produces certain sounds, particularly velar consonant, palatal consonant, palatalized, postalveolar consonant, alveolo-palatal consonant, and uvular consonants.	Palate Template:Infobox Anatomy Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] # Overview The palate (Template:IPAEng) is the roof of the mouth in humans and vertebrate animals. It separates the oral cavity from the nasal cavity. The palate is divided into two parts, the anterior bony hard palate, and the posterior fleshy soft palate or velum. The maxillary nerve branch of the trigeminal nerve (V) supplies sensory innervation to the palate. # Etymology The name is middle English and is probably derived from the Latin palatum or the Old French palat. # Function When functioning in conjunction with other parts of the mouth the palate produces certain sounds, particularly velar consonant, palatal consonant, palatalized, postalveolar consonant, alveolo-palatal consonant, and uvular consonants.	https://www.wikidoc.org/index.php/Palate
e29b7d8e187b36abb4942de43dd4e5d08e7afd96	wikidoc	Pannus	Pannus Pannus is a medical term for a hanging flap of tissue. When involving the stomach, it is called a Panniculus and consists of skin, fat, and sometimes contents of the internal abdomen as part of a hernia. A pannus can be the result of loose hanging tissues after pregnancy or weight loss. It can also be the deformity of obesity. A pannus can come in many different sizes and shapes and can get very large hanging down below the knees. The extra tissue of a hanging pannus can make personal hygiene difficult. Skin conditions such as yeast infections under the pannus are common problems. A massive hanging pannus can get in the way of walking. A smaller pannus can be an annoyance with clothing as the individual sits or stands. Pannus can be removed by plastic surgery operation called a panniculectomy (which is a type of tummy tuck). In people suffering from rheumatoid arthritis, pannus tissue eventually forms in the joint affected by the disease, causing loss of bone and cartilage. In ophthalmology, "'pannus'" refers to the growth of blood vessels into the peripheral cornea. In normal individuals, the cornea is avascular. Chronic local hypoxia (such as that occurring with overuse of contact lenses) or inflammation may lead to peripheral corneal vascularization, or pannus. Pannus may also develop in diseases of the corneal stem cells, such as aniridia. It is often solved by peritomy.	Pannus Pannus is a medical term for a hanging flap of tissue. When involving the stomach, it is called a Panniculus and consists of skin, fat, and sometimes contents of the internal abdomen as part of a hernia. A pannus can be the result of loose hanging tissues after pregnancy or weight loss. It can also be the deformity of obesity. A pannus can come in many different sizes and shapes and can get very large hanging down below the knees. The extra tissue of a hanging pannus can make personal hygiene difficult. Skin conditions such as yeast infections under the pannus are common problems. A massive hanging pannus can get in the way of walking. A smaller pannus can be an annoyance with clothing as the individual sits or stands. Pannus can be removed by plastic surgery operation called a panniculectomy (which is a type of tummy tuck). In people suffering from rheumatoid arthritis, pannus tissue eventually forms in the joint affected by the disease, causing loss of bone and cartilage. In ophthalmology, "'pannus'" refers to the growth of blood vessels into the peripheral cornea. In normal individuals, the cornea is avascular. Chronic local hypoxia (such as that occurring with overuse of contact lenses) or inflammation may lead to peripheral corneal vascularization, or pannus. Pannus may also develop in diseases of the corneal stem cells, such as aniridia. It is often solved by peritomy.	https://www.wikidoc.org/index.php/Pannus
c11a9a321c8ed569d8058b36e8e3b3b480a7c849	wikidoc	Papain	Papain Papain is a cysteine protease (EC 3.4.22.2) hydrolase enzyme present in papaya (Carica papaya) and mountain papaya (Vasconcellea cundinamarcensis). # Structure It consists of 212 amino acids stabilised by 3 disulfide bridges. Its 3D structure consists of 2 distinct structural domains with a cleft between them. This cleft contains the active site, which contains a catalytic triad that has been likened to that of chymotrypsin. Its catalytic triad is made up of 3 amino acids - cysteine-25 (from which it gets its classification), histidine-159, and asparagine-158. # Function The mechanism by which it breaks peptide bonds involves deprotonation of Cys-25 by His-159. Asn-158 helps to orient the imidazole ring of His-159 to allow this deprotonation to take place. Cys-25 then performs a nucleophilic attack on the carbonyl carbon of a peptide backbone. This frees the amino terminal of the peptide, and forms a covalent acyl-enzyme intermediate. The enzyme is then deacylated by a water molecule, and releases the carboxy terminal portion of the peptide. In immunology, papain is known to cleave the Fc (crystallisable) portion of immunoglobulins (antibodies) from the Fab (antigen-binding) portion. # Uses Its utility is in breaking down the tough meat fibers and has been utilized for thousands of years in its native South America. It is sold as a component in powdered meat tenderizer available in most supermarkets. Papain, in the form of a meat tenderizer such as Adolph's, made into a paste with water, is also a home remedy treatment for jellyfish, bee, yellow jacket (wasps) stings and possibly stingray wounds, breaking down the protein toxins in the venom. It is also the main ingredient in Stop Itch and Stop Itch Plus, a DermaTech Laboratories first aid cream popular in Australia. Papain is used to dissociate cells in the first step of cell culture preparations. A 10 minute treatment of small tissue pieces (less than 1 mm cubed) will allow papain to begin breaking down the extracellular matrix molecules holding the cells together. After 10 minutes, the tissue should be treated with a protease inhibitor solution to stop the protease action (if left untreated papain's activity will lead to complete lysis of the cells). The tissue must then be triturated (passed quickly up and down through a Pasteur pipette) in order to break up the pieces of tissue into a single cell suspension. It is also used as an ingredient in various enzymatic debriding preparations, notably Accuzyme. These are used in the care of some chronic wounds to clean up dead tissue. It can also be found as an ingredient in some toothpastes or mints as teeth-whitener. Its whitening effect in toothpastes and mints however is minimal, because the papain is present in low concentrations, and will be quickly diluted by saliva. It would take several months of using the whitening product to have noticeably whiter teeth. # Immunoglobulins An antibody digested by papain yields three fragments, two 50 kDa Fab fragments and one 50kDa Fc fragment. The agents are not approved by the FDA, and according to the latest FDA position/policy papers these products are not legally marketed. # Production Papain is usually produced as a crude, dried material by collecting the latex from the fruit of the papaya tree. The latex is collected after scoring the neck of the fruit where it may either dry on the fruit or drip into a container. This latex is then further dried. It is now classified as a dried, crude material. A purification step is necessary to remove contaminating substances. This purification consists of the solubilization and extraction of the active papain enzyme system through a government registered process. This purified papain may be supplied as powder or as liquid.	Papain Papain is a cysteine protease (EC 3.4.22.2) hydrolase enzyme present in papaya (Carica papaya) and mountain papaya (Vasconcellea cundinamarcensis). # Structure It consists of 212[1] amino acids stabilised by 3 disulfide bridges. Its 3D structure consists of 2 distinct structural domains with a cleft between them. This cleft contains the active site, which contains a catalytic triad that has been likened to that of chymotrypsin. Its catalytic triad is made up of 3 amino acids - cysteine-25 (from which it gets its classification), histidine-159, and asparagine-158. # Function The mechanism by which it breaks peptide bonds involves deprotonation of Cys-25 by His-159. Asn-158 helps to orient the imidazole ring of His-159 to allow this deprotonation to take place. Cys-25 then performs a nucleophilic attack on the carbonyl carbon of a peptide backbone. This frees the amino terminal of the peptide, and forms a covalent acyl-enzyme intermediate. The enzyme is then deacylated by a water molecule, and releases the carboxy terminal portion of the peptide. In immunology, papain is known to cleave the Fc (crystallisable) portion of immunoglobulins (antibodies) from the Fab (antigen-binding) portion. # Uses Its utility is in breaking down the tough meat fibers and has been utilized for thousands of years in its native South America. It is sold as a component in powdered meat tenderizer available in most supermarkets. Papain, in the form of a meat tenderizer such as Adolph's, made into a paste with water, is also a home remedy treatment for jellyfish, bee, yellow jacket (wasps) stings and possibly stingray wounds, breaking down the protein toxins in the venom. It is also the main ingredient in Stop Itch and Stop Itch Plus, a DermaTech Laboratories first aid cream popular in Australia. Papain is used to dissociate cells in the first step of cell culture preparations. A 10 minute treatment of small tissue pieces (less than 1 mm cubed) will allow papain to begin breaking down the extracellular matrix molecules holding the cells together. After 10 minutes, the tissue should be treated with a protease inhibitor solution to stop the protease action (if left untreated papain's activity will lead to complete lysis of the cells). The tissue must then be triturated (passed quickly up and down through a Pasteur pipette) in order to break up the pieces of tissue into a single cell suspension. It is also used as an ingredient in various enzymatic debriding preparations, notably Accuzyme. These are used in the care of some chronic wounds to clean up dead tissue. It can also be found as an ingredient in some toothpastes or mints as teeth-whitener. Its whitening effect in toothpastes and mints however is minimal, because the papain is present in low concentrations, and will be quickly diluted by saliva. It would take several months of using the whitening product to have noticeably whiter teeth. # Immunoglobulins An antibody digested by papain yields three fragments, two 50 kDa Fab fragments and one 50kDa Fc fragment. The agents are not approved by the FDA, and according to the latest FDA position/policy papers these products are not legally marketed. # Production Papain is usually produced as a crude, dried material by collecting the latex from the fruit of the papaya tree. The latex is collected after scoring the neck of the fruit where it may either dry on the fruit or drip into a container. This latex is then further dried. It is now classified as a dried, crude material. A purification step is necessary to remove contaminating substances. This purification consists of the solubilization and extraction of the active papain enzyme system through a government registered process. This purified papain may be supplied as powder or as liquid. # External links - Papain at the US National Library of Medicine Medical Subject Headings (MeSH) - drugdigest- info on papin - Papain Applications, Inhibitors and Substrates	https://www.wikidoc.org/index.php/Papain
e83ec77cc09883f200d6843bea90ceedd2859db3	wikidoc	Papaya	Papaya The papaya (from Carib via Spanish), is the fruit of the tree Carica papaya, in the genus Carica. It is native to the tropics of the Americas, and was cultivated in Mexico several centuries before the emergence of the Mesoamerican classic cultures. Nowadays, the papaya is also known as fruta bomba (Cuba), lechosa (Venezuela, Puerto Rico, the Philippines and the Dominican Republic), mamão, papaw (Sri Lankan English), Papol \ Guslabu (Tree melon - in Sinhalese ), pawpaw or tree melon, as well as tree melon (木瓜) in Chinese and đu đủ in Vietnamese. It is a small tree, the single stem growing from 5 to 10 m tall, with spirally arranged leaves confined to the top of the trunk; the lower trunk is conspicuously scarred where leaves and fruit were borne. The leaves are large, 50-70 cm diameter, deeply palmately lobed with 7 lobes. The tree is usually unbranched if unlopped. The flowers are similar in shape to the flowers of the Plumeria but are much smaller and wax like. They appear on the axils of the leaves, maturing into the large 15-45 cm long, 10-30 cm diameter fruit. The fruit is ripe when it feels soft (like a ripe avocado or a bit softer) and its skin has attained an amber to orange hue. The fruit's taste is vaguely similar to pineapple and peach, although much milder without the tartness, creamier, and more fragrant, with a texture of slightly over-ripened cantaloupe. # Cultivation and uses Originally from southern Mexico, Central America and northern South America, the papaya is now cultivated in most countries with a tropical climate like Brazil, India, South Africa, Sri Lanka and the Philippines. The ripe fruit is usually eaten raw, without the skin or seeds. The unripe green fruit of papaya can be eaten cooked, usually in curries, salads and stews. Papaya is rich in an enzyme called papain, a protease which is useful in tenderizing meat and other proteins. Its ability to break down tough meat fibers was utilized for thousands of years by indigenous Americans. It is included as a component in powdered meat tenderizers, and is also marketed in tablet form to remedy digestive problems. Papain is also popular (in countries where it grows) as a topical application in the treatment of cuts, rashes, stings and burns. Papain ointment is commonly made from fermented papaya flesh, and is applied as a gel-like paste. Harrison Ford was treated for a ruptured disc incurred during filming of Indiana Jones and the Temple of Doom by having papain injected into his back. Caution should be taken when harvesting, as papaya is known to release a latex fluid when not quite ripe, which can cause irritation and provoke allergic reaction in some people. The papaya fruit and leaves also contains carpaine, an anthelmintic alkaloid which could be dangerous in high doses. Women in India, Pakistan, Sri Lanka, and other parts of the world have long used papaya as a folk remedy for contraception and abortion. Medical research in animals has confirmed the contraceptive and abortifacient capability of papaya, and also found that papaya seeds have contraceptive effects in adult male langur monkeys, possibly in adult male humans as well. Unripe papaya is especially effective in large amounts or high doses. Papaya is not teratogenic and will not cause miscarriage in small, ripe amounts. Phytochemicals in papaya may suppress the effects of progesterone. The black seeds are edible and have a sharp, spicy taste. They are sometimes ground up and used as a substitute for black pepper. In some parts of Asia the young leaves of papaya are steamed and eaten like spinach. Excessive consumption of papaya, as of carrots, can cause carotenemia, the yellowing of soles and palms which is otherwise harmless. The papaya fruit is susceptible to the Papaya Fruit Fly. This wasp-like fly lays its eggs in young fruit. # Ethnomedical uses - The mature (ripe) fruit treats ringworm, green fruits treat high blood pressure, and are used as an aphrodisiac. - The fruit can be directly applied topically to skin sores . - The seeds are anti-inflammatory and analgesic, and they are used to treat stomachache and fungal infections. - The leaves are used as a heart tonic, analgesic, and to treat stomachache. - The roots are used as an analgesic. ## Diseases	Papaya The papaya (from Carib via Spanish), is the fruit of the tree Carica papaya, in the genus Carica. It is native to the tropics of the Americas, and was cultivated in Mexico several centuries before the emergence of the Mesoamerican classic cultures. Nowadays, the papaya is also known as fruta bomba (Cuba), lechosa (Venezuela, Puerto Rico, the Philippines and the Dominican Republic), mamão, papaw (Sri Lankan English), Papol \ Guslabu (Tree melon - in Sinhalese ), pawpaw or tree melon, as well as tree melon (木瓜) in Chinese and đu đủ in Vietnamese. It is a small tree, the single stem growing from 5 to 10 m tall, with spirally arranged leaves confined to the top of the trunk; the lower trunk is conspicuously scarred where leaves and fruit were borne. The leaves are large, 50-70 cm diameter, deeply palmately lobed with 7 lobes. The tree is usually unbranched if unlopped. The flowers are similar in shape to the flowers of the Plumeria but are much smaller and wax like. They appear on the axils of the leaves, maturing into the large 15-45 cm long, 10-30 cm diameter fruit. The fruit is ripe when it feels soft (like a ripe avocado or a bit softer) and its skin has attained an amber to orange hue. The fruit's taste is vaguely similar to pineapple and peach, although much milder without the tartness, creamier, and more fragrant, with a texture of slightly over-ripened cantaloupe.[citation needed] # Cultivation and uses Originally from southern Mexico, Central America and northern South America, the papaya is now cultivated in most countries with a tropical climate like Brazil, India, South Africa, Sri Lanka and the Philippines. The ripe fruit is usually eaten raw, without the skin or seeds. The unripe green fruit of papaya can be eaten cooked, usually in curries, salads and stews. Papaya is rich in an enzyme called papain, a protease which is useful in tenderizing meat and other proteins. Its ability to break down tough meat fibers was utilized for thousands of years by indigenous Americans. It is included as a component in powdered meat tenderizers, and is also marketed in tablet form to remedy digestive problems. Papain is also popular (in countries where it grows) as a topical application in the treatment of cuts, rashes, stings and burns. Papain ointment is commonly made from fermented papaya flesh, and is applied as a gel-like paste. Harrison Ford was treated for a ruptured disc incurred during filming of Indiana Jones and the Temple of Doom by having papain injected into his back.[1] Caution should be taken when harvesting, as papaya is known to release a latex fluid when not quite ripe, which can cause irritation and provoke allergic reaction in some people. The papaya fruit and leaves also contains carpaine, an anthelmintic alkaloid which could be dangerous in high doses. Women in India, Pakistan, Sri Lanka, and other parts of the world have long used papaya as a folk remedy for contraception and abortion.[citation needed] Medical research in animals has confirmed the contraceptive and abortifacient capability of papaya, and also found that papaya seeds have contraceptive effects in adult male langur monkeys, possibly in adult male humans as well.[2] Unripe papaya is especially effective in large amounts or high doses. Papaya is not teratogenic and will not cause miscarriage in small, ripe amounts. Phytochemicals in papaya may suppress the effects of progesterone.[3] The black seeds are edible and have a sharp, spicy taste. They are sometimes ground up and used as a substitute for black pepper. In some parts of Asia the young leaves of papaya are steamed and eaten like spinach. Excessive consumption of papaya, as of carrots, can cause carotenemia, the yellowing of soles and palms which is otherwise harmless.[citation needed] The papaya fruit is susceptible to the Papaya Fruit Fly. This wasp-like fly lays its eggs in young fruit. # Ethnomedical uses - The mature (ripe) fruit treats ringworm, green fruits treat high blood pressure, and are used as an aphrodisiac. - The fruit can be directly applied topically to skin sores [1]. - The seeds are anti-inflammatory and analgesic, and they are used to treat stomachache and fungal infections[1]. - The leaves are used as a heart tonic, analgesic, and to treat stomachache[1]. - The roots are used as an analgesic[2]. ## Diseases	https://www.wikidoc.org/index.php/Papaya
33aefe4d84af35fd4dadd7da5e7271448b1a7f77	wikidoc	Papule	Papule A papule is a small, solid and usually conical elevation of the skin. Papules do not contain pus, which distinguishes them from pustules. Papules often occur in clusters and can accompany rashes. A condition that causes a papule is called a "Papulosis". Examples of papuloses include: - Lymphomatoid papulosis - Bowenoid papulosis - Clear cell papulosis # Causes Papules can be caused by: - Inflammation (which in turn is often caused by infection or abrasion of the skin) - Accumulated secretion of skin tissue (hyperplasia) or glandular fluids. - Presence of an infection such as disseminated histoplasmosis. - Hypertrophy of skin cells - Acne - Drugs like Azficel-T	Papule A papule is a small, solid and usually conical elevation of the skin. Papules do not contain pus, which distinguishes them from pustules. Papules often occur in clusters and can accompany rashes. A condition that causes a papule is called a "Papulosis". Examples of papuloses include: - Lymphomatoid papulosis - Bowenoid papulosis - Clear cell papulosis # Causes Papules can be caused by: - Inflammation (which in turn is often caused by infection or abrasion of the skin) - Accumulated secretion of skin tissue (hyperplasia) or glandular fluids. - Presence of an infection such as disseminated histoplasmosis. - Hypertrophy of skin cells - Acne - Drugs like Azficel-T	https://www.wikidoc.org/index.php/Papule
ed378757e9c80e9909688ae9fe02495de3f28b83	wikidoc	Patent	Patent A patent is a set of exclusive rights granted by a state to an inventor or his assignee for a fixed period of time in exchange for a disclosure of an invention. The procedure for granting patents, the requirements placed on the patentee and the extent of the exclusive rights vary widely between countries according to national laws and international agreements. Typically, however, a patent application must include one or more claims defining the invention which must be new, inventive, and useful or industrially applicable. In many countries, certain subject areas are excluded from patents, such as business methods and mental acts. The exclusive right granted to a patentee in most countries is the right to prevent or exclude others from making, using, selling, offering to sell or importing the invention. # Definition The term patent usually refers to a right granted to anyone who invents or discovers any new and useful process, machine, article of manufacture, or composition of matter, or any new and useful improvement thereof. The additional qualification utility patents is used in countries such as the United States to distinguish them from other types of patents but should not be confused with utility models granted by other countries. Examples of particular species of patents for inventions include biological patents, business method patents, chemical patents and software patents. Some other types of intellectual property rights are referred to as patents in some jurisdictions: industrial design rights are called design patents in some jurisdictions (they protect the visual design of objects that are not purely utilitarian), plant breeders' rights are sometimes called plant patents, and utility models or Gebrauchsmuster are sometimes called petty patents or innovation patents. This article relates primarily to the patent for an invention, although so-called petty patents and utility models may also be granted for inventions. Certain grants made by the monarch in pursuance of the royal prerogative were sometimes called letters patent, which was a government notice to the public of a grant of an exclusive right to ownership and possession. These were often grants of a patent-like monopoly and predate the modern British origins of the patent system. For other uses of the term patent see Land patents, which were land grants by early state governments in the USA. This reflects the original meaning of letters patent that had a broader scope than current usage. # Law ## Effects A patent is not a right to practice or use the invention. Rather, a patent provides the right to exclude others from making, using, selling, offering for sale, or importing the patented invention for the term of the patent, which is usually 20 years from the filing date. A patent is, in effect, a limited property right that the government offers to inventors in exchange for their agreement to share the details of their inventions with the public. Like any other property right, it may be sold, licensed, mortgaged, assigned or transferred, given away, or simply abandoned. The rights conveyed by a patent vary country-by-country. For example, in the United States, a patent covers research, except "purely philosophical" inquiry. A U.S. patent is infringed by any "making" of the invention, even a making that goes toward development of a new invention — which may itself become subject of a patent. In contrast, Australian law permits others to build on top of a patented invention, by carving out exceptions from infringement for those who conduct research (e.g. for academic purposes) on the invention. A patent being an exclusionary right does not, however, necessarily give the owner of the patent the right to exploit the patent. For example, many inventions are improvements of prior inventions which may still be covered by someone else's patent. If an inventor takes an existing, patented mouse trap design, adds a new feature to make an improved mouse trap, and obtains a patent on the improvement, he or she can only legally build his or her improved mouse trap with permission from the patent holder of the original mouse trap, assuming the original patent is still in force. On the other hand, the owner of the improved mouse trap can exclude the original patent owner from using the improvement. Some countries have "working provisions" which require that the invention be exploited in the jurisdiction it covers. Consequences of not working an invention vary from one country to another, ranging from revocation of the patent rights to the awarding of a compulsory license awarded by the courts to a party wishing to exploit a patented invention. The patentee has the opportunity to challenge the revocation or license, but is usually required to provide evidence that the reasonable requirements of the public have been met by the working of invention. ## Enforcement Patents can generally only be enforced through civil lawsuits (for example, for a US patent, by an action for patent infringement in a United States federal court), although some territories (such as France and Austria) have criminal penalties for wanton infringement. Typically, the patent owner will seek monetary compensation for past infringement, and will seek an injunction prohibiting the defendant from engaging in future acts of infringement. In order to prove infringement, the patent owner must establish that the accused infringer practices all of the requirements of at least one of the claims of the patent (noting that in many jurisdictions the scope of the patent may not be limited to what is literally stated in the claims, for example due to the "doctrine of equivalents"). An important limitation on the ability of a patent owner to successfully assert the patent in civil litigation is the accused infringer's right to challenge the validity of that patent. Civil courts hearing patent cases can and often do declare patents invalid. The grounds on which a patent can be found invalid are set out in the relevant patent legislation and vary between countries. Often, the grounds are a sub-set of the requirements for patentability in the relevant country. Whilst an infringer is generally free to rely on any available ground of invalidity (such as a prior publication, for example), some countries have sanctions to prevent the same validity questions being relitigated. An example is the UK Certificate of contested validity. The vast majority of patent rights, however, are not determined through litigation, but are resolved privately through patent licensing. Patent licensing agreements are effectively contracts in which the patent owner (the licensor) agrees not to sue the licensee for infringement of the licensor's patent rights, usually in return for a royalty or other payment. It is common for companies engaged in complex technical fields to enter into dozens of license agreements associated with the production of a single product. Moreover, it is equally common for competitors in such fields to license patents to each other under cross-licensing agreements in order to gain access to each other's patents. A cross license agreement could be highly desirable to the mouse trap developers discussed above, for example, because it would permit both parties to profit off each other's inventions. The United Nations Statistics Division reports that USA was the top market for patents in force in 2000 closely followed by the EU and Japan. ## Ownership In most countries, both natural persons and corporate entities may apply for a patent. The entity or entities then become the owners of the patent when and if it issues. However, it is nearly always required that the inventor or inventors be named and an indication be given on the public record as to how the owner or owners acquired their rights to the invention from the inventor or inventors. In the United States, however, only the natural person(s) (i.e. the inventor/s) may apply for a patent. If a patent issues, then each person listed as an inventor owns the patent separately from the other. For example, if two inventors are listed on a patent, then each one may grant licenses to the patent independently of the other, absent an agreement to the contrary. It is common in the United States for inventors to assign their ownership rights to a corporate entity. Inventors that work for a corporation, for example, often are required to assign their ownership rights to their corporation as a condition of their employment. Independent inventors often assign their ownership rights to a single entity so that only one entity has the right to grant a license. The ability to assign ownership rights increases the liquidity of a patent as property. Inventors can obtain patents and then sell them to third parties. The third parties then own the patents as if they had originally made the inventions themselves. ## Governing laws The grant and enforcement of patents are governed by national laws, and also by international treaties, where those treaties have been given effect in national laws. Patents are, therefore, territorial in nature. Commonly, a nation forms a patent office with responsibility for operating that nation's patent system, within the relevant patent laws. The patent office generally has responsibility for the grant of patents, with infringement being the remit of national courts. There is a trend towards global harmonization of patent laws, with the World Trade Organization (WTO) being particularly active in this area. The TRIPs Agreement has been largely successful in providing a forum for nations to agree on an aligned set of patent laws. Conformity with the TRIPs agreement is a requirement of admission to the WTO and so compliance is seen by many nations as important. This has also led to many developing nations, which may historically have developed different laws to aid their development, enforcing patents laws in line with global practice. A key international convention relating to patents is the Paris Convention for the Protection of Industrial Property, initially signed in 1883. The Paris Convention sets out a range of basic rules relating to patents, and although the convention does not have direct legal effect in all national jurisdictions, the principles of the convention are incorporated into all notable current patent systems. The most significant aspect of the convention is the provision of the right to claim priority: filing an application in any one member state of the Paris Convention preserves the right for one year to file in any other member state, and receive the benefit of the original filing date. Because the right to a patent is intensely date-driven, this right is fundamental to modern patent usage. The authority for patent statutes in different countries varies. In the United States, the Constitution empowers Congress to make laws to "promote the Progress of Science and useful Arts..." The laws Congress passed are codified in title 35 of the United States Code and created the United States Patent and Trademark Office. In the UK, substantive patent law is contained in the Patents Act 1977 as amended. In addition, there are international treaty procedures, such as the procedures under the European Patent Convention (EPC) , and the Patent Cooperation Treaty (PCT) (administered by WIPO and covering 137 countries), that centralise some portion of the filing and examination procedure. Similar arrangements exist among the member states of ARIPO, OAPI, the analogous treaties among African countries. ## Application A patent is requested by filing a written application at the relevant patent office. The application contains a description of how to make and use the invention and, under some legislations, if not self evident, the usefulness of the invention. The patent application may or must also comprise "claims". Claims define the invention and embodiments for which the applicant wants patent rights. To obtain a patent, an applicant must provide a written description of the invention in sufficient detail for a person skilled in the art (i.e., the relevant area of technology) to make and use the invention. This written description is provided in what is known as the patent specification, which is often accompanied by illustrating drawings. Some countries, such as the United States, further require that the specification disclose the "best mode" of the invention (i.e., the most effective way, to the best of the inventor's knowledge, to make or practice the invention). In addition, at the end of the specification, the applicant must provide one or more claims that define what the applicant regards as their invention. A claim, unlike the body of the specification, is a description designed to provide the public with notice of precisely what the patent owner has a right to exclude others from making, using, or selling. Claims are often analogized to a deed or other instrument that, in the context of real property, sets the metes and bounds of an owner's right to exclude. The claims define what a patent covers. A single patent may contain numerous claims, each of which is regarded as a distinct invention. For a patent to be granted, that is to take legal effect, the patent application must meet the legal requirements related to patentability. Once a patent application has been filed, most patent offices examine the application for compliance with the requirements of the relevant patent law. If the application does not comply, the objections are usually communicated to the applicant or their patent agent or attorney, who can respond to the objections to attempt to overcome them and obtain the grant of the patent. In most countries, there is no requirement that the inventor build a prototype or otherwise reduce his or her invention to actual practice in order to obtain a patent. The description of the invention, however, must be sufficiently complete so that another person with ordinary skill in the art of the invention can make and use the invention without undue experimentation. Once granted the patent is subject in most countries to renewal fees, generally due each year, to keep the patent in force. In Egbert v. Lippmann,104 U. S. 333 (1881) (the "corset case"), the United States Supreme Court affirmed a decision that an inventor who had "slept on his rights for eleven years" without applying for a patent could not obtain one at that time. This decision has been codified as 35. U.S.C. §102, which bars an inventor from obtaining a patent if the invention has been in public use for more than one year prior to filing. ## Prosecution # Economics ## Rationale There are four primary incentives embodied in the patent system: to invent in the first place; to disclose the invention once made; to invest the sums necessary to experiment, produce and market the invention; and to design around and improve upon earlier patents. - Patents provide incentives for economically efficient research and development (R&D). Many large modern corporations have annual R&D budgets of hundreds of millions or even billions of dollars. Without patents, R&D spending would be significantly less or eliminated altogether, limiting the possibility of technological advances or breakthroughs. Corporations would be much more conservative about the R&D investments they made, as third parties would be free to exploit any developments. This second justification is closely related to the basic ideas underlying traditional property rights. - In accordance with the original definition of the term "patent," patents facilitate and encourage disclosure of innovations into the public domain for the common good. If inventors did not have the legal protection of patents, in many cases, they would prefer or tend to keep their inventions secret. Awarding patents generally makes the details of new technology publicly available, for exploitation by anyone after the patent expires, or for further improvement by other inventors. Furthermore, when a patent's term has expired, the public record ensures that the patentee's idea is not lost to humanity. - In many industries (especially those with high fixed costs and either low marginal costs or low reverse engineering costs — computer processors, software, and pharmaceuticals for example), once an invention exists, the cost of commercialization (testing, tooling up a factory, developing a market, etc.) is far more than the initial conception cost. (For example, the internal "rule of thumb" at several computer companies in the 1980s was that post-R&D costs were 7-to-1). Unless there is some way to prevent copies from competing at the marginal cost of production, companies will not make that productization investment. - Patent rights create an incentive for companies to develop workarounds to patented inventions, thereby creating improved or alternative technologies that might not otherwise be developed. One interesting side effect of modern patent usage is that the small-time inventor can use the exclusive right status to become a licensor. This allows the inventor to accumulate capital quickly from licensing the invention and may allow rapid innovation to occur because he or she may choose to not manage a manufacturing buildup for the invention. Thus the inventor's time and energy can be spent on pure innovation, allowing others to concentrate on manufacturability. ## Criticism While each of the four incentives is achieved by the patent system in some contexts, the patent system has countervailing costs, and those costs fall more heavily in some contexts than others. There are many critics and criticisms of patents and this has resulted in the formation of a large number of groups who oppose patents in general, or specific types of patents, and who lobby for their abolishment. Patents have always been criticized for being granted on already known inventions. In 1938, for example, R. Buckminster Fuller, inventor of the geodesic dome wrote: Patents have also been criticized for conferring a "negative right" upon a patent owner, permitting them to exclude competitors from using or exploiting the invention, even if the competitor subsequently develops the same invention independently. This may be subsequent to the date of invention, or to the priority date, depending upon the relevant patent law (see First to file and first to invent). Patents may hinder innovation as well. A holding company, pejoratively known as a "patent troll", owns a portfolio of patents, and sues others for infringement of these patents while doing little to develop the technology itself. Another theoretical problem with patent rights was proposed by law professors Michael Heller and Rebecca Sue Eisenberg in a 1998 Science article. Building from Heller's theory of the tragedy of the anticommons, the professors postulated that intellectual property rights may become so fragmented that, effectively, no one can take advantage of them as to do so would require an agreement between the owners of all of the fragments. Since at least the early 1980s, patent offices have accepted that computer programs can lie within the realm of patentable subject matter, although the regulations for when a computer program is a patentable invention differ markedly between countries. In response to perceived problems with the grant of patents, and the evolving nature of technology and industry, there is debate about, and reform of, patent systems around the world. The TRIPs agreement, developed by the WTO has led to the alignment of many patent systems with regard to certain controversial issues, such as what can be protected by patents and the issue of compulsory licences in cases of national need. # Etymology The term "patent" originates from the Latin word patere which means "to lay open" (i.e., make available for public inspection) and the term letters patent, which originally denoted royal decrees granting exclusive rights to certain individuals or businesses. # History There is evidence suggesting that something like patents was used among some ancient Greek cities. The creator of a new recipe was granted an exclusive right to make the food for one year, and a similar practice existed in some Roman cities. Patents in the modern sense originated in Italy in 1474. At that time the Republic of Venice issued a decree by which new and inventive devices, once they had been put into practice, had to be communicated to the Republic in order to obtain the right to prevent others from using them. England followed with the Statute of Monopolies in 1623 under King James I, which declared that patents could only be granted for "projects of new invention." During the reign of Queen Anne (1702–1714), the lawyers of the English Court developed the requirement that a written description of the invention must be submitted. These developments, which were in place during the Colonial period, formed the basis for modern English and United States patent law. In the United States, during the colonial period and Articles of Confederation years (1778–1789), several states adopted patent systems of their own. The first Congress adopted a Patent Act, in 1790, and the first patent was issued under this Act on July 31, 1790 (and the subject matter of that patent was for the making of potash).	Patent A patent is a set of exclusive rights granted by a state to an inventor or his assignee for a fixed period of time in exchange for a disclosure of an invention. The procedure for granting patents, the requirements placed on the patentee and the extent of the exclusive rights vary widely between countries according to national laws and international agreements. Typically, however, a patent application must include one or more claims defining the invention which must be new, inventive, and useful or industrially applicable. In many countries, certain subject areas are excluded from patents, such as business methods and mental acts. The exclusive right granted to a patentee in most countries is the right to prevent or exclude others from making, using, selling, offering to sell or importing the invention. # Definition The term patent usually refers to a right granted to anyone who invents or discovers any new and useful process, machine, article of manufacture, or composition of matter, or any new and useful improvement thereof. The additional qualification utility patents is used in countries such as the United States to distinguish them from other types of patents but should not be confused with utility models granted by other countries. Examples of particular species of patents for inventions include biological patents, business method patents, chemical patents and software patents. Some other types of intellectual property rights are referred to as patents in some jurisdictions: industrial design rights are called design patents in some jurisdictions (they protect the visual design of objects that are not purely utilitarian), plant breeders' rights are sometimes called plant patents, and utility models or Gebrauchsmuster are sometimes called petty patents or innovation patents. This article relates primarily to the patent for an invention, although so-called petty patents and utility models may also be granted for inventions. Certain grants made by the monarch in pursuance of the royal prerogative were sometimes called letters patent, which was a government notice to the public of a grant of an exclusive right to ownership and possession. These were often grants of a patent-like monopoly and predate the modern British origins of the patent system. For other uses of the term patent see Land patents, which were land grants by early state governments in the USA. This reflects the original meaning of letters patent that had a broader scope than current usage. # Law ## Effects A patent is not a right to practice or use the invention.[1] Rather, a patent provides the right to exclude others[1] from making, using, selling, offering for sale, or importing the patented invention for the term of the patent, which is usually 20 years from the filing date. A patent is, in effect, a limited property right that the government offers to inventors in exchange for their agreement to share the details of their inventions with the public. Like any other property right, it may be sold, licensed, mortgaged, assigned or transferred, given away, or simply abandoned. The rights conveyed by a patent vary country-by-country. For example, in the United States, a patent covers research, except "purely philosophical" inquiry. A U.S. patent is infringed by any "making" of the invention, even a making that goes toward development of a new invention — which may itself become subject of a patent. In contrast, Australian law permits others to build on top of a patented invention, by carving out exceptions from infringement for those who conduct research (e.g. for academic purposes) on the invention.[2] A patent being an exclusionary right does not, however, necessarily give the owner of the patent the right to exploit the patent.[1] For example, many inventions are improvements of prior inventions which may still be covered by someone else's patent.[1] If an inventor takes an existing, patented mouse trap design, adds a new feature to make an improved mouse trap, and obtains a patent on the improvement, he or she can only legally build his or her improved mouse trap with permission from the patent holder of the original mouse trap, assuming the original patent is still in force. On the other hand, the owner of the improved mouse trap can exclude the original patent owner from using the improvement. Some countries have "working provisions" which require that the invention be exploited in the jurisdiction it covers. Consequences of not working an invention vary from one country to another, ranging from revocation of the patent rights to the awarding of a compulsory license awarded by the courts to a party wishing to exploit a patented invention. The patentee has the opportunity to challenge the revocation or license, but is usually required to provide evidence that the reasonable requirements of the public have been met by the working of invention. ## Enforcement Patents can generally only be enforced through civil lawsuits (for example, for a US patent, by an action for patent infringement in a United States federal court), although some territories (such as France and Austria) have criminal penalties for wanton infringement.[3] Typically, the patent owner will seek monetary compensation for past infringement, and will seek an injunction prohibiting the defendant from engaging in future acts of infringement. In order to prove infringement, the patent owner must establish that the accused infringer practices all of the requirements of at least one of the claims of the patent (noting that in many jurisdictions the scope of the patent may not be limited to what is literally stated in the claims, for example due to the "doctrine of equivalents"). An important limitation on the ability of a patent owner to successfully assert the patent in civil litigation is the accused infringer's right to challenge the validity of that patent. Civil courts hearing patent cases can and often do declare patents invalid. The grounds on which a patent can be found invalid are set out in the relevant patent legislation and vary between countries. Often, the grounds are a sub-set of the requirements for patentability in the relevant country. Whilst an infringer is generally free to rely on any available ground of invalidity (such as a prior publication, for example), some countries have sanctions to prevent the same validity questions being relitigated. An example is the UK Certificate of contested validity. The vast majority of patent rights, however, are not determined through litigation, but are resolved privately through patent licensing. Patent licensing agreements are effectively contracts in which the patent owner (the licensor) agrees not to sue the licensee for infringement of the licensor's patent rights, usually in return for a royalty or other payment. It is common for companies engaged in complex technical fields to enter into dozens of license agreements associated with the production of a single product. Moreover, it is equally common for competitors in such fields to license patents to each other under cross-licensing agreements in order to gain access to each other's patents. A cross license agreement could be highly desirable to the mouse trap developers discussed above, for example, because it would permit both parties to profit off each other's inventions. The United Nations Statistics Division reports that USA was the top market for patents in force in 2000 closely followed by the EU and Japan. ## Ownership In most countries, both natural persons and corporate entities may apply for a patent. The entity or entities then become the owners of the patent when and if it issues. However, it is nearly always required that the inventor or inventors be named and an indication be given on the public record as to how the owner or owners acquired their rights to the invention from the inventor or inventors. In the United States, however, only the natural person(s) (i.e. the inventor/s) may apply for a patent. If a patent issues, then each person listed as an inventor owns the patent separately from the other. For example, if two inventors are listed on a patent, then each one may grant licenses to the patent independently of the other, absent an agreement to the contrary. It is common in the United States for inventors to assign their ownership rights to a corporate entity.[4] Inventors that work for a corporation, for example, often are required to assign their ownership rights to their corporation as a condition of their employment. Independent inventors often assign their ownership rights to a single entity so that only one entity has the right to grant a license. The ability to assign ownership rights increases the liquidity of a patent as property. Inventors can obtain patents and then sell them to third parties. The third parties then own the patents as if they had originally made the inventions themselves. ## Governing laws Template:Sidebar with heading backgrounds The grant and enforcement of patents are governed by national laws, and also by international treaties, where those treaties have been given effect in national laws. Patents are, therefore, territorial in nature. Commonly, a nation forms a patent office with responsibility for operating that nation's patent system, within the relevant patent laws. The patent office generally has responsibility for the grant of patents, with infringement being the remit of national courts. There is a trend towards global harmonization of patent laws, with the World Trade Organization (WTO) being particularly active in this area. The TRIPs Agreement has been largely successful in providing a forum for nations to agree on an aligned set of patent laws. Conformity with the TRIPs agreement is a requirement of admission to the WTO and so compliance is seen by many nations as important. This has also led to many developing nations, which may historically have developed different laws to aid their development, enforcing patents laws in line with global practice. A key international convention relating to patents is the Paris Convention for the Protection of Industrial Property, initially signed in 1883. The Paris Convention sets out a range of basic rules relating to patents, and although the convention does not have direct legal effect in all national jurisdictions, the principles of the convention are incorporated into all notable current patent systems. The most significant aspect of the convention is the provision of the right to claim priority: filing an application in any one member state of the Paris Convention preserves the right for one year to file in any other member state, and receive the benefit of the original filing date. Because the right to a patent is intensely date-driven, this right is fundamental to modern patent usage. The authority for patent statutes in different countries varies. In the United States, the Constitution empowers Congress to make laws to "promote the Progress of Science and useful Arts..." The laws Congress passed are codified in title 35 of the United States Code and created the United States Patent and Trademark Office.[5] In the UK, substantive patent law is contained in the Patents Act 1977 as amended.[6] In addition, there are international treaty procedures, such as the procedures under the European Patent Convention (EPC) [administered by the European Patent Organisation (EPOrg)], and the Patent Cooperation Treaty (PCT) (administered by WIPO and covering 137 countries), that centralise some portion of the filing and examination procedure. Similar arrangements exist among the member states of ARIPO, OAPI, the analogous treaties among African countries. ## Application A patent is requested by filing a written application at the relevant patent office. The application contains a description of how to make and use the invention and, under some legislations, if not self evident, the usefulness of the invention. The patent application may or must also comprise "claims". Claims define the invention and embodiments for which the applicant wants patent rights. To obtain a patent, an applicant must provide a written description of the invention in sufficient detail for a person skilled in the art (i.e., the relevant area of technology) to make and use the invention. This written description is provided in what is known as the patent specification, which is often accompanied by illustrating drawings. Some countries, such as the United States, further require that the specification disclose the "best mode" of the invention (i.e., the most effective way, to the best of the inventor's knowledge, to make or practice the invention).[7] In addition, at the end of the specification, the applicant must provide one or more claims that define what the applicant regards as their invention. A claim, unlike the body of the specification, is a description designed to provide the public with notice of precisely what the patent owner has a right to exclude others from making, using, or selling. Claims are often analogized to a deed or other instrument that, in the context of real property, sets the metes and bounds of an owner's right to exclude. The claims define what a patent covers. A single patent may contain numerous claims, each of which is regarded as a distinct invention. For a patent to be granted, that is to take legal effect, the patent application must meet the legal requirements related to patentability. Once a patent application has been filed, most patent offices examine the application for compliance with the requirements of the relevant patent law. If the application does not comply, the objections are usually communicated to the applicant or their patent agent or attorney, who can respond to the objections to attempt to overcome them and obtain the grant of the patent. In most countries, there is no requirement that the inventor build a prototype or otherwise reduce his or her invention to actual practice in order to obtain a patent. The description of the invention, however, must be sufficiently complete so that another person with ordinary skill in the art of the invention can make and use the invention without undue experimentation. Once granted the patent is subject in most countries to renewal fees, generally due each year,[8] to keep the patent in force. In Egbert v. Lippmann,104 U. S. 333 (1881) (the "corset case"), the United States Supreme Court affirmed a decision that an inventor who had "slept on his rights for eleven years" without applying for a patent could not obtain one at that time. This decision has been codified as 35. U.S.C. §102, which bars an inventor from obtaining a patent if the invention has been in public use for more than one year prior to filing. ## Prosecution # Economics Template:Tfd ## Rationale There are four primary incentives embodied in the patent system: to invent in the first place; to disclose the invention once made; to invest the sums necessary to experiment, produce and market the invention; and to design around and improve upon earlier patents.[9] - Patents provide incentives for economically efficient research and development (R&D). Many large modern corporations have annual R&D budgets of hundreds of millions or even billions of dollars. Without patents, R&D spending would be significantly less or eliminated altogether, limiting the possibility of technological advances or breakthroughs. Corporations would be much more conservative about the R&D investments they made, as third parties would be free to exploit any developments. This second justification is closely related to the basic ideas underlying traditional property rights. - In accordance with the original definition of the term "patent," patents facilitate and encourage disclosure of innovations into the public domain for the common good. If inventors did not have the legal protection of patents, in many cases, they would prefer or tend to keep their inventions secret. Awarding patents generally makes the details of new technology publicly available, for exploitation by anyone after the patent expires, or for further improvement by other inventors. Furthermore, when a patent's term has expired, the public record ensures that the patentee's idea is not lost to humanity. - In many industries (especially those with high fixed costs and either low marginal costs or low reverse engineering costs — computer processors, software, and pharmaceuticals for example), once an invention exists, the cost of commercialization (testing, tooling up a factory, developing a market, etc.) is far more than the initial conception cost. (For example, the internal "rule of thumb" at several computer companies in the 1980s was that post-R&D costs were 7-to-1). Unless there is some way to prevent copies from competing at the marginal cost of production, companies will not make that productization investment. - Patent rights create an incentive for companies to develop workarounds to patented inventions, thereby creating improved or alternative technologies that might not otherwise be developed. One interesting side effect of modern patent usage is that the small-time inventor can use the exclusive right status to become a licensor. This allows the inventor to accumulate capital quickly from licensing the invention and may allow rapid innovation to occur because he or she may choose to not manage a manufacturing buildup for the invention. Thus the inventor's time and energy can be spent on pure innovation, allowing others to concentrate on manufacturability. ## Criticism While each of the four incentives is achieved by the patent system in some contexts, the patent system has countervailing costs, and those costs fall more heavily in some contexts than others. There are many critics and criticisms of patents and this has resulted in the formation of a large number of groups who oppose patents in general, or specific types of patents, and who lobby for their abolishment. Patents have always been criticized for being granted on already known inventions. In 1938, for example, R. Buckminster Fuller, inventor of the geodesic dome wrote:[10] Patents have also been criticized for conferring a "negative right" upon a patent owner, permitting them to exclude competitors from using or exploiting the invention, even if the competitor subsequently develops the same invention independently. This may be subsequent to the date of invention, or to the priority date, depending upon the relevant patent law (see First to file and first to invent).[citation needed] Patents may hinder innovation as well. A holding company, pejoratively known as a "patent troll", owns a portfolio of patents, and sues others for infringement of these patents while doing little to develop the technology itself.[citation needed] Another theoretical problem with patent rights was proposed by law professors Michael Heller and Rebecca Sue Eisenberg in a 1998 Science article.[11] Building from Heller's theory of the tragedy of the anticommons, the professors postulated that intellectual property rights may become so fragmented that, effectively, no one can take advantage of them as to do so would require an agreement between the owners of all of the fragments. Since at least the early 1980s, patent offices have accepted that computer programs can lie within the realm of patentable subject matter, although the regulations for when a computer program is a patentable invention differ markedly between countries. In response to perceived problems with the grant of patents, and the evolving nature of technology and industry, there is debate about, and reform of, patent systems around the world. The TRIPs agreement, developed by the WTO has led to the alignment of many patent systems with regard to certain controversial issues, such as what can be protected by patents and the issue of compulsory licences in cases of national need. # Etymology The term "patent" originates from the Latin word patere which means "to lay open" (i.e., make available for public inspection) and the term letters patent, which originally denoted royal decrees granting exclusive rights to certain individuals or businesses. # History There is evidence suggesting that something like patents was used among some ancient Greek cities. The creator of a new recipe was granted an exclusive right to make the food for one year, and a similar practice existed in some Roman cities.[citation needed] Patents in the modern sense originated in Italy in 1474.[13] At that time the Republic of Venice issued a decree by which new and inventive devices, once they had been put into practice, had to be communicated to the Republic in order to obtain the right to prevent others from using them.[14] England followed with the Statute of Monopolies in 1623 under King James I, which declared that patents could only be granted for "projects of new invention." During the reign of Queen Anne (1702–1714), the lawyers of the English Court developed the requirement that a written description of the invention must be submitted.[15] These developments, which were in place during the Colonial period, formed the basis for modern English and United States patent law. In the United States, during the colonial period and Articles of Confederation years (1778–1789), several states adopted patent systems of their own. The first Congress adopted a Patent Act, in 1790, and the first patent was issued under this Act on July 31, 1790 (and the subject matter of that patent was for the making of potash).	https://www.wikidoc.org/index.php/Patent
f6d6c606d09ca1c19321ffa3034f0d45d9f30495	wikidoc	Pawpaw	Pawpaw # Overview Pawpaw (Asimina) is a genus of eight or nine species of small trees with large leaves and fruit, native to eastern North America. The genus includes the largest edible fruit indigenous to the continent. They are understory trees found in deep fertile bottomland and hilly upland habitat. Pawpaw is in the same family (Annonaceae) as the custard-apple, cherimoya, sweetsop, and soursop, and it is the only member of that family not confined to the tropics. # Names The name, also spelled paw paw, paw-paw, and papaw, probably derives from the Spanish papaya, perhaps due to the superficial similarity of their fruit. Pawpaw has numerous other common names, often very local, such as prairie banana, Indiana banana, Kentucky banana, Michigan banana, and Ozark banana. # Description The pawpaws are shrubs or small trees, reaching heights of 2 to 12 m tall. The northern, cold-tolerant common pawpaw (Asimina triloba) is deciduous, while the southern species are often evergreen. The leaves are alternate, simple ovate, entire, 20 to 35 cm long and 10 to 15 cm broad. The fetid flowers are produced singly or in clusters of up to eight together; they are large, 4 to 6 cm across, perfect, with six sepals and petals (three large outer petals, three smaller inner petals). The petal color varies from white to purple or red-brown. The fruit is a large edible berry, 5 to 16 cm long and 3 to 7 cm broad, weighing from 20 to 500 g, with numerous seeds; it is green when unripe, maturing to yellow or brown. It has a flavor somewhat similar to both banana and mango, varying significantly by cultivar, and has more protein than most fruits. - Bark: Dark brown, blotched with gray spots, sometimes covered with small excrescences, divided by shallow fissures. Inner bark tough, fibrous. Branchlets light brown, tinged with red, marked by shallow grooves. - Wood: Pale, greenish yellow, sapwood lighter; light, soft, coarse-grained and spongy. Sp. gr., 0.3969; weight of cu. ft. 24.74 lbs. - Winter buds: Small, brown, acuminate, hairy. - Leaves: Alternate, simple, feather-veined, obovate-lanceolate, ten to twelve inches long, four to five broad, wedge-shaped at base, entire, acute at apex; midrib and primary veins prominent. They come out of the bud conduplicate, green, covered with rusty tomentum beneath, hairy above; when full grown are smooth, dark green above, paler beneath. In autumn they are a rusty yellow. Petioles short and stout with a prominent adaxial groove. Stipules wanting. - Flowers: April, with the leaves. Perfect, solitary, axillary, rich red purple, two inches across, borne on stout, hairy peduncles. Ill smelling. - Calyx: Sepals three, valvate in bud, ovate, acuminate, pale green, downy. - Corolla: Petals six, in two rows, imbricate in the bud. Inner row acute, erect, nectariferous. Outer row broadly ovate, reflexed at maturity. Petals at first are green, then brown, and finally become dull purple and conspicuously veiny. - Stamens: Indefinite, densely packed on the globular receptacle. Filaments short; anthers extrorse, two-celled, opening longitudinally. - Pistils: Several, on the summit of the receptacle, projecting from the mass of stamens. Ovary one-celled; stigma sessile; ovules many. - Fruit: September, October. Cotyledons broad, five-lobed. # Cultivation Pollinated by scavenging carrion flies and beetles, the flowers emit a weak scent which attracts few pollinators, thus limiting fruit production. Larger growers sometimes locate rotting meat near the trees at bloom time to increase the number of blowflies. Asimina triloba is the only larval host of the Zebra Swallowtail Butterfly. # Species - Asimina angustifolia Raf. - Slimleaf Pawpaw. Florida, Georgia, and Alabama. - Asimina incana (W. Bartram) Exell - Woolly Pawpaw. Florida and Georgia. - Asimina obovata (Willd.) Nash - Bigflower Pawpaw. Florida. - Asimina parviflora (Michx.) Dunal - Smallflower Pawpaw. Southern states from Texas to Virginia. - Asimina pygmea (W. Bartram) Dunal - Dwarf Pawpaw. Florida and Georgia. - Asimina reticulata Shuttlw. ex Chapman - Netted Pawpaw. Florida and Georgia. - Asimina tetramera Small - Fourpetal Pawpaw. Florida Template:StatusEndangered. - Asimina triloba (L.) Dunal - Common Pawpaw. Extreme southern Ontario, Canada, and the eastern United States from New York west to southeast Nebraska, and south to northern Florida and eastern Texas. # Cultivation and uses The pawpaw's chosen home is in the shade of the rich bottom lands of the Mississippi valley, where it often forms a dense undergrowth in the forest. Where it dominates a tract it appears as a thicket of small slender trees, whose great leaves are borne so close together at the ends of the branches, and which cover each other so symmetrically, that the effect is to give a peculiar imbricated appearance to the tree. Although it is a delicious and nutritious fruit, it has never been cultivated on the scale of apples and peaches, primarily because it does not store or ship well. It is also difficult to transplant due to its long taproot. Cultivars are propagated by chip budding or whip grafting. In recent years the pawpaw has attracted renewed interest, particularly among organic growers, as a native fruit which has few pests, and which therefore requires little pesticide use for cultivation. The shipping and storage problem has largely been addressed by pulping the fruit and freezing the pulp. Among backyard gardeners it also is gaining in popularity because of the appeal of fresh fruit and because it is relatively low maintenance once planted. The pulp is used primarily in baked dessert recipes, as well as for brewing pawpaw beer. The commercial growing and harvesting of pawpaws is strongest in southeast Ohio. The Ohio Pawpaw Growers' Association annually sponsors the Ohio Pawpaw Festival at Lake Snowden near Albany, Ohio. The flowers are self-incompatible, requiring cross pollination; at least two different varieties of the plant are needed as pollenizers. The flowers produce an odor similar to that of rotting meat to attract blowflies or carrion beetles for cross pollination. Lack of pollination is the most common cause of poor fruiting, and growers resort to hand pollination or to hanging chicken necks or other meat to attract pollinators. The leaves, twigs, and bark of the tree also contain natural insecticides known as acetogenins, which can be used to make an organic pesticide. Acetogenins from pawpaw have also been investigated for their potent anticancer effects stemming from their ability to inhibit NADH oxidase. This colonial tree has a strong tendency to form colonial thickets if left unchecked. # History The earliest documentation of pawpaws is in the 1541 report of the de Soto expedition, who found Native Americans cultivating it east of the Mississippi River. The Lewis and Clark Expedition depended and sometimes subsisted on pawpaws during their travels. Chilled pawpaw fruit was a favorite dessert of George Washington, and Thomas Jefferson was certainly familiar with it as he planted it at Monticello. In 2006, following lobbying by the Ohio Pawpaw Growers' Association, the Ohio House of Representatives passed a law that would have declared the pawpaw to be the state native fruit of Ohio. However, the Ohio Senate failed to act on the bill, resulting in its death. # Medicinal properties Compounds found in the bark and leaves of the pawpaw tree have been investigated and tested for anti-cancer properties because of the chemicals' effect on cell metabolism , particularly by Dr Jerry McLaughlin and his team at Purdue University . Growers hope that potential medical use will eventually lead to increased market demand from the pharmaceutical industry. In homeopathy, Asimina triloba is used as remedy for scarlet fever and red skin rashes. The seeds also have insecticidal properties. The Native Americans dried and powdered them and applied the powder to childrens' heads to control lice; specialized shampoos now use compounds from pawpaw for the same purpose. Recent research has shown that the consumption of Annonaceous fruit may lead to the onset of atypical Parkinson's Disease in human, and a subsequent study has suggested a possible involvement of phytochemicals in the onset of symptoms in rats. Further research is currently underway to investigate the relationship between Annonaceous compounds and neurodegeneration.	Pawpaw # Overview Pawpaw (Asimina) is a genus of eight or nine species of small trees with large leaves and fruit, native to eastern North America. The genus includes the largest edible fruit indigenous to the continent. They are understory trees found in deep fertile bottomland and hilly upland habitat. Pawpaw is in the same family (Annonaceae) as the custard-apple, cherimoya, sweetsop, and soursop, and it is the only member of that family not confined to the tropics. # Names The name, also spelled paw paw, paw-paw, and papaw, probably derives from the Spanish papaya, perhaps due to the superficial similarity of their fruit. Pawpaw has numerous other common names, often very local, such as prairie banana, Indiana banana, Kentucky banana, Michigan banana, and Ozark banana. # Description The pawpaws are shrubs or small trees, reaching heights of 2 to 12 m tall. The northern, cold-tolerant common pawpaw (Asimina triloba) is deciduous, while the southern species are often evergreen. The leaves are alternate, simple ovate, entire, 20 to 35 cm long and 10 to 15 cm broad. The fetid flowers are produced singly or in clusters of up to eight together; they are large, 4 to 6 cm across, perfect, with six sepals and petals (three large outer petals, three smaller inner petals). The petal color varies from white to purple or red-brown. The fruit is a large edible berry, 5 to 16 cm long and 3 to 7 cm broad, weighing from 20 to 500 g, with numerous seeds; it is green when unripe, maturing to yellow or brown. It has a flavor somewhat similar to both banana and mango, varying significantly by cultivar, and has more protein than most fruits. - Bark: Dark brown, blotched with gray spots, sometimes covered with small excrescences, divided by shallow fissures. Inner bark tough, fibrous. Branchlets light brown, tinged with red, marked by shallow grooves. - Wood: Pale, greenish yellow, sapwood lighter; light, soft, coarse-grained and spongy. Sp. gr., 0.3969; weight of cu. ft. 24.74 lbs. - Winter buds: Small, brown, acuminate, hairy. - Leaves: Alternate, simple, feather-veined, obovate-lanceolate, ten to twelve inches long, four to five broad, wedge-shaped at base, entire, acute at apex; midrib and primary veins prominent. They come out of the bud conduplicate, green, covered with rusty tomentum beneath, hairy above; when full grown are smooth, dark green above, paler beneath. In autumn they are a rusty yellow. Petioles short and stout with a prominent adaxial groove. Stipules wanting. - Flowers: April, with the leaves. Perfect, solitary, axillary, rich red purple, two inches across, borne on stout, hairy peduncles. Ill smelling. - Calyx: Sepals three, valvate in bud, ovate, acuminate, pale green, downy. - Corolla: Petals six, in two rows, imbricate in the bud. Inner row acute, erect, nectariferous. Outer row broadly ovate, reflexed at maturity. Petals at first are green, then brown, and finally become dull purple and conspicuously veiny. - Stamens: Indefinite, densely packed on the globular receptacle. Filaments short; anthers extrorse, two-celled, opening longitudinally. - Pistils: Several, on the summit of the receptacle, projecting from the mass of stamens. Ovary one-celled; stigma sessile; ovules many. - Fruit: September, October. Cotyledons broad, five-lobed.[1] # Cultivation Pollinated by scavenging carrion flies and beetles, the flowers emit a weak scent which attracts few pollinators, thus limiting fruit production. Larger growers sometimes locate rotting meat near the trees at bloom time to increase the number of blowflies. Asimina triloba is the only larval host of the Zebra Swallowtail Butterfly. # Species - Asimina angustifolia Raf. - Slimleaf Pawpaw. Florida, Georgia, and Alabama. - Asimina incana (W. Bartram) Exell - Woolly Pawpaw. Florida and Georgia. - Asimina obovata (Willd.) Nash - Bigflower Pawpaw. Florida. - Asimina parviflora (Michx.) Dunal - Smallflower Pawpaw. Southern states from Texas to Virginia. - Asimina pygmea (W. Bartram) Dunal - Dwarf Pawpaw. Florida and Georgia. - Asimina reticulata Shuttlw. ex Chapman - Netted Pawpaw. Florida and Georgia. - Asimina tetramera Small - Fourpetal Pawpaw. Florida Template:StatusEndangered. - Asimina triloba (L.) Dunal - Common Pawpaw. Extreme southern Ontario, Canada, and the eastern United States from New York west to southeast Nebraska, and south to northern Florida and eastern Texas. # Cultivation and uses The pawpaw's chosen home is in the shade of the rich bottom lands of the Mississippi valley, where it often forms a dense undergrowth in the forest. Where it dominates a tract it appears as a thicket of small slender trees, whose great leaves are borne so close together at the ends of the branches, and which cover each other so symmetrically, that the effect is to give a peculiar imbricated appearance to the tree.[1] Although it is a delicious and nutritious fruit, it has never been cultivated on the scale of apples and peaches, primarily because it does not store or ship well. It is also difficult to transplant due to its long taproot. Cultivars are propagated by chip budding or whip grafting. In recent years the pawpaw has attracted renewed interest, particularly among organic growers, as a native fruit which has few pests, and which therefore requires little pesticide use for cultivation. The shipping and storage problem has largely been addressed by pulping the fruit and freezing the pulp. Among backyard gardeners it also is gaining in popularity because of the appeal of fresh fruit and because it is relatively low maintenance once planted. The pulp is used primarily in baked dessert recipes, as well as for brewing pawpaw beer. The commercial growing and harvesting of pawpaws is strongest in southeast Ohio. The Ohio Pawpaw Growers' Association annually sponsors the Ohio Pawpaw Festival at Lake Snowden near Albany, Ohio. The flowers are self-incompatible, requiring cross pollination; at least two different varieties of the plant are needed as pollenizers. The flowers produce an odor similar to that of rotting meat to attract blowflies or carrion beetles for cross pollination. Lack of pollination is the most common cause of poor fruiting, and growers resort to hand pollination or to hanging chicken necks or other meat to attract pollinators. The leaves, twigs, and bark of the tree also contain natural insecticides known as acetogenins, which can be used to make an organic pesticide[citation needed]. Acetogenins from pawpaw have also been investigated for their potent anticancer effects stemming from their ability to inhibit NADH oxidase. This colonial tree has a strong tendency to form colonial thickets if left unchecked. # History The earliest documentation of pawpaws is in the 1541 report of the de Soto expedition, who found Native Americans cultivating it east of the Mississippi River. The Lewis and Clark Expedition depended and sometimes subsisted on pawpaws during their travels. Chilled pawpaw fruit was a favorite dessert of George Washington, and Thomas Jefferson was certainly familiar with it as he planted it at Monticello. In 2006, following lobbying by the Ohio Pawpaw Growers' Association, the Ohio House of Representatives passed a law that would have declared the pawpaw to be the state native fruit of Ohio. However, the Ohio Senate failed to act on the bill, resulting in its death. # Medicinal properties Compounds found in the bark and leaves of the pawpaw tree have been investigated and tested for anti-cancer properties because of the chemicals' effect on cell metabolism [1], particularly by Dr Jerry McLaughlin and his team at Purdue University [2]. Growers hope that potential medical use will eventually lead to increased market demand from the pharmaceutical industry. In homeopathy, Asimina triloba is used as remedy for scarlet fever and red skin rashes.[citation needed] The seeds also have insecticidal properties. The Native Americans dried and powdered them and applied the powder to childrens' heads to control lice; specialized shampoos now use compounds from pawpaw for the same purpose. Recent research has shown that the consumption of Annonaceous fruit may lead to the onset of atypical Parkinson's Disease in human, and a subsequent study has suggested a possible involvement of phytochemicals in the onset of symptoms in rats. Further research is currently underway to investigate the relationship between Annonaceous compounds and neurodegeneration.[2][3][4][5]	https://www.wikidoc.org/index.php/Pawpaw
4b27d0eb27106a2a0cab9881669144ca2e2901a2	wikidoc	Pectin	Pectin # Disclaimer WikiDoc MAKES NO GUARANTEE OF VALIDITY. WikiDoc is not a professional health care provider, nor is it a suitable replacement for a licensed healthcare provider. WikiDoc is intended to be an educational tool, not a tool for any form of healthcare delivery. The educational content on WikiDoc drug pages is based upon the FDA package insert, National Library of Medicine content and practice guidelines / consensus statements. WikiDoc does not promote the administration of any medication or device that is not consistent with its labeling. Please read our full disclaimer here. NOTE: Most over the counter (OTC) are not reviewed and approved by the FDA. However, they may be marketed if they comply with applicable regulations and policies. FDA has not evaluated whether this product complies. # Overview Pectin is a demulcent that is FDA approved for the treatment of symptoms associated with sore mouth and sore throat. Common adverse reactions include diarrhea, gas, and loose stools. # Adult Indications and Dosage ## FDA-Labeled Indications and Dosage (Adult) # Indications Temporarily relieves the following symptoms associated with sore mouth and sore throat: - Minor discomfort - Irritated areas # Dosage - Adults: dissolve 1 or 2 drops (one at a time) slowly in the mouth. Repeat as needed. ## Off-Label Use and Dosage (Adult) ### Guideline-Supported Use There is limited information regarding Off-Label Guideline-Supported Use of Pectin in adult patients. ### Non–Guideline-Supported Use There is limited information regarding Off-Label Non–Guideline-Supported Use of Pectin in adult patients. # Pediatric Indications and Dosage ## FDA-Labeled Indications and Dosage (Pediatric) # Indications Temporarily relieves the following symptoms associated with sore mouth and sore throat: - Minor discomfort - Irritated areas # Dosage - Children 5 years and over: dissolve 1 or 2 drops (one at a time) slowly in the mouth. Repeat as needed. - Children under 5 years, ask a doctor. ## Off-Label Use and Dosage (Pediatric) ### Guideline-Supported Use There is limited information regarding Off-Label Guideline-Supported Use of Pectin in pediatric patients. ### Non–Guideline-Supported Use There is limited information regarding Off-Label Non–Guideline-Supported Use of Pectin in pediatric patients. # Contraindications There is limited information regarding Contraindications of Pectin in patientspatients. # Warnings Sore throat warning: if sore throat is severe, persists for more than 2 days, is accompanied or followed by fever, headache, rash, swelling, nausea, or vomiting, consult a doctor promptly. These may be serious. # Adverse Reactions ## Clinical Trials Experience There is limited information regarding Adverse Reactions of Pectin in patients. ## Postmarketing Experience There is limited information regarding postmarketing experience of Pectin in patients. # Drug Interactions There is limited information regarding of Pectin in patients. # Use in Specific Populations ### Pregnancy Pregnancy Category (FDA): There is limited information regarding FDA Pregnancy Category/i> of Pectin in patients. Pregnancy Category (AUS): There is limited information regarding Australian pregnancy category/i> of Pectin in patients. ### Labor and Delivery There is no FDA guidance on use of Pectin during labor and delivery. ### Nursing Mothers There is no FDA guidance on the use of Pectin in women who are nursing. ### Pediatric Use There is no FDA guidance on the use of Pectin in pediatric settings. ### Geriatic Use There is no FDA guidance on the use of Pectin in geriatric settings. ### Gender There is no FDA guidance on the use of Pectin with respect to specific gender populations. ### Race There is no FDA guidance on the use of Pectin with respect to specific racial populations. ### Renal Impairment There is no FDA guidance on the use of Pectin in patients with renal impairment. ### Hepatic Impairment There is no FDA guidance on the use of Pectin in patients with hepatic impairment. ### Females of Reproductive Potential and Males There is no FDA guidance on the use of Pectin in women of reproductive potentials and males. ### Immunocompromised Patients There is no FDA guidance one the use of Pectin in patients who are immunocompromised. ### Others # Administration and Monitoring ### Administration - Oral ### Monitoring There is limited information regarding Pectin Monitoring in the drug label. # IV Compatibility There is limited information regarding the compatibility of Pectin and IV administrations. # Overdosage There is limited information regarding drug overdose/i> of Pectin in patients # Pharmacology There is limited information regarding Pectin Pharmacology in the drug label. ## Mechanism of Action There is limited information regarding Pectin Mechanism of Action in the drug label. ## Structure There is limited information regarding Pectin Structure in the drug label. ## Pharmacodynamics There is limited information regarding Pectin Pharmacodynamics in the drug label. ## Pharmacokinetics There is limited information regarding Pectin Pharmacokinetics in the drug label. ## Nonclinical Toxicology There is limited information regarding Pectin Nonclinical Toxicology in the drug label. # Clinical Studies There is limited information regarding Pectin Clinical Studies in the drug label. # How Supplied There is limited information regarding Pectin How Supplied in the drug label. ## Storage There is limited information regarding Pectin Storage in the drug label. # Images ## Drug Images ## Package and Label Display Panel # Patient Counseling Information STOP USE AND ASK A DOCTOR IF - Sore mouth does not improve in 7 days - Irritation, pain, or redness persists or worsens # Precautions with Alcohol Alcohol-Pectin interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication. # Brand Names BREEZERS COOL BERRY # Look-Alike Drug Names There is limited information regarding Pectin Look-Alike Drug Names in the drug label. # Drug Shortage Status Drug Shortage # Price	Pectin Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Kiran Singh, M.D. [2] # Disclaimer WikiDoc MAKES NO GUARANTEE OF VALIDITY. WikiDoc is not a professional health care provider, nor is it a suitable replacement for a licensed healthcare provider. WikiDoc is intended to be an educational tool, not a tool for any form of healthcare delivery. The educational content on WikiDoc drug pages is based upon the FDA package insert, National Library of Medicine content and practice guidelines / consensus statements. WikiDoc does not promote the administration of any medication or device that is not consistent with its labeling. Please read our full disclaimer here. NOTE: Most over the counter (OTC) are not reviewed and approved by the FDA. However, they may be marketed if they comply with applicable regulations and policies. FDA has not evaluated whether this product complies. # Overview Pectin is a demulcent that is FDA approved for the treatment of symptoms associated with sore mouth and sore throat. Common adverse reactions include diarrhea, gas, and loose stools. # Adult Indications and Dosage ## FDA-Labeled Indications and Dosage (Adult) # Indications Temporarily relieves the following symptoms associated with sore mouth and sore throat: - Minor discomfort - Irritated areas # Dosage - Adults: dissolve 1 or 2 drops (one at a time) slowly in the mouth. Repeat as needed. ## Off-Label Use and Dosage (Adult) ### Guideline-Supported Use There is limited information regarding Off-Label Guideline-Supported Use of Pectin in adult patients. ### Non–Guideline-Supported Use There is limited information regarding Off-Label Non–Guideline-Supported Use of Pectin in adult patients. # Pediatric Indications and Dosage ## FDA-Labeled Indications and Dosage (Pediatric) # Indications Temporarily relieves the following symptoms associated with sore mouth and sore throat: - Minor discomfort - Irritated areas # Dosage - Children 5 years and over: dissolve 1 or 2 drops (one at a time) slowly in the mouth. Repeat as needed. - Children under 5 years, ask a doctor. ## Off-Label Use and Dosage (Pediatric) ### Guideline-Supported Use There is limited information regarding Off-Label Guideline-Supported Use of Pectin in pediatric patients. ### Non–Guideline-Supported Use There is limited information regarding Off-Label Non–Guideline-Supported Use of Pectin in pediatric patients. # Contraindications There is limited information regarding Contraindications of Pectin in patientspatients. # Warnings Sore throat warning: if sore throat is severe, persists for more than 2 days, is accompanied or followed by fever, headache, rash, swelling, nausea, or vomiting, consult a doctor promptly. These may be serious. # Adverse Reactions ## Clinical Trials Experience There is limited information regarding Adverse Reactions of Pectin in patients. ## Postmarketing Experience There is limited information regarding postmarketing experience of Pectin in patients. # Drug Interactions There is limited information regarding <Drug Interactions/i> of Pectin in patients. # Use in Specific Populations ### Pregnancy Pregnancy Category (FDA): There is limited information regarding FDA Pregnancy Category/i> of Pectin in patients. Pregnancy Category (AUS): There is limited information regarding Australian pregnancy category/i> of Pectin in patients. ### Labor and Delivery There is no FDA guidance on use of Pectin during labor and delivery. ### Nursing Mothers There is no FDA guidance on the use of Pectin in women who are nursing. ### Pediatric Use There is no FDA guidance on the use of Pectin in pediatric settings. ### Geriatic Use There is no FDA guidance on the use of Pectin in geriatric settings. ### Gender There is no FDA guidance on the use of Pectin with respect to specific gender populations. ### Race There is no FDA guidance on the use of Pectin with respect to specific racial populations. ### Renal Impairment There is no FDA guidance on the use of Pectin in patients with renal impairment. ### Hepatic Impairment There is no FDA guidance on the use of Pectin in patients with hepatic impairment. ### Females of Reproductive Potential and Males There is no FDA guidance on the use of Pectin in women of reproductive potentials and males. ### Immunocompromised Patients There is no FDA guidance one the use of Pectin in patients who are immunocompromised. ### Others # Administration and Monitoring ### Administration - Oral ### Monitoring There is limited information regarding Pectin Monitoring in the drug label. # IV Compatibility There is limited information regarding the compatibility of Pectin and IV administrations. # Overdosage There is limited information regarding drug overdose/i> of Pectin in patients # Pharmacology There is limited information regarding Pectin Pharmacology in the drug label. ## Mechanism of Action There is limited information regarding Pectin Mechanism of Action in the drug label. ## Structure There is limited information regarding Pectin Structure in the drug label. ## Pharmacodynamics There is limited information regarding Pectin Pharmacodynamics in the drug label. ## Pharmacokinetics There is limited information regarding Pectin Pharmacokinetics in the drug label. ## Nonclinical Toxicology There is limited information regarding Pectin Nonclinical Toxicology in the drug label. # Clinical Studies There is limited information regarding Pectin Clinical Studies in the drug label. # How Supplied There is limited information regarding Pectin How Supplied in the drug label. ## Storage There is limited information regarding Pectin Storage in the drug label. # Images ## Drug Images ## Package and Label Display Panel # Patient Counseling Information STOP USE AND ASK A DOCTOR IF - Sore mouth does not improve in 7 days - Irritation, pain, or redness persists or worsens # Precautions with Alcohol Alcohol-Pectin interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication. # Brand Names BREEZERS COOL BERRY # Look-Alike Drug Names There is limited information regarding Pectin Look-Alike Drug Names in the drug label. # Drug Shortage Status Drug Shortage # Price	https://www.wikidoc.org/index.php/Pectin
77b6769df2c4e1e8e5edebad6ea1921b626133a2	wikidoc	Pedant	Pedant A pedant, or pædant, is a person who is overly concerned with formalism and precision, or who makes a show of learning. The corresponding (obsolete) female noun is pedantess. The term comes from the French pédant (1566 in Darme & Hatzfeldster's Dictionnaire général de la langue française) or its source Italian pedante "teacher," schoolmaster, pedant. (Compare the Spanish pedante.). The origin of the Italian term is uncertain. The first element is apparently the same as in pedagogue (a teacher) etc.; and it has been suggested that pedante was contracted from the medieval Latin pædagogans, present participle of pædagogare "to act as pedagogue, to teach" (Du Cange); but evidence is wanting. The Latin word is derived from Greek παιδαγογός, < παιδ- "child" + αγειν "to lead", which originally referred to a slave who led children to and from school but later meant "a source of instruction or guidance". # Negative connotation The term is typically used with a negative connotation, indicating someone overly concerned with minutiae detail and whose tone is perceived as condescending. When it was first used by Shakespeare in Love's Labour's Lost (1588), it simply meant "teacher". Shortly afterward, it began to be used negatively. Thomas Nashe wrote in Have with you to Saffron-walden (1596), page 43: "O, tis a precious apothegmaticall Pedant, who will finde matter inough to dilate a whole daye of the first inuention of Fy, fa, fum" # Usage of term Being referred to as a pedant, or pedantic, is generally considered insulting. However some people take pride in being a pedant, especially with regard to the use of the English language. In an attempt to avoid censure, people who wish to make a correction might preface it with "not wishing to be pedantic, but ..." or "without being a pedant, ...". Pedantry can also be an indication of certain developmental disorders. In particular those with high-functioning autism, often have behavior characterized by pedantic speech. Those with Asperger's tend to obsess over the minutiae of subjects, and are prone to giving long detailed expositions, and the related corrections, and may gravitate to careers in academia or science where such obsessive attention to detail is often functional and rewarded. # Obsessive-compulsive personality disorder Obsessive-compulsive personality disorder is also in part characterized by a form of pedantry that is overly concerned with the correct following of rules, procedures and practices. Sometimes the rules that OCPD sufferers obsessively follow are of their own devising, or are corruptions or re-interpretations of the letter of actual rules. # Quotations - "A Man who has been brought up among Books, and is able to talk of nothing else, is what we call a Pedant. But, methinks, we should enlarge the Title, and give it to every one that does not know how to think out of his Profession and particular way of Life." - Addison, Spectator 1711. - "Nothing is as peevish and pedantic as men's judgments of one another." - Desiderius Erasmus - "The pedant is he who finds it impossible to read criticism of himself, without immediately reaching for his pen and replying to the effect that the accusation is a gross insult to his person. He is, in effect, a man unable to laugh at himself." - Sigmund Freud, The Ego and the Id. - "Servile and impertinent, shallow and pedantic, a bigot and sot" - Thomas Macaulay, describing James Boswell - "The term, then, is obviously a relative one: my pedantry is your scholarship, his reasonable accuracy, her irreducible minimum of education and someone else’s ignorance." H. W. Fowler, Modern English Usage - "It's not pedantry, but merely a desire for accuracy." - Roy Cropper, in an episode of Coronation Street. - "Pedantic, I?" - Alexei Sayle - "The only other thing is that I am a pendant went it comes to written English and I would like to proof-read anything that can viewed outside the company." - Garty Vicksters - "He can be pedantic, he can be pedantic." - George Costanza, in The Big Salad episode of Seinfeld - "I find this meatloaf rather shallow and pedantic." - Peter Griffin, in Petarted episode of Family Guy	Pedant A pedant, or pædant, is a person who is overly concerned with formalism and precision, or who makes a show of learning. The corresponding (obsolete) female noun is pedantess. The term comes from the French pédant (1566 in Darme & Hatzfeldster's Dictionnaire général de la langue française) or its source Italian pedante "teacher," schoolmaster, pedant. (Compare the Spanish pedante.). The origin of the Italian term is uncertain. The first element is apparently the same as in pedagogue (a teacher) etc.; and it has been suggested[citation needed] that pedante was contracted from the medieval Latin pædagogans, present participle of pædagogare "to act as pedagogue, to teach" (Du Cange); but evidence is wanting. The Latin word is derived from Greek παιδαγογός, < παιδ- "child" + αγειν "to lead", which originally referred to a slave who led children to and from school but later meant "a source of instruction or guidance".[1] # Negative connotation The term is typically used with a negative connotation, indicating someone overly concerned with minutiae detail and whose tone is perceived as condescending. When it was first used by Shakespeare in Love's Labour's Lost (1588), it simply meant "teacher". Shortly afterward, it began to be used negatively. Thomas Nashe wrote in Have with you to Saffron-walden (1596), page 43: "O, tis a precious apothegmaticall [terse] Pedant, who will finde matter inough to dilate a whole daye of the first inuention [invention] of Fy, fa, fum" # Usage of term Being referred to as a pedant, or pedantic, is generally considered insulting.[citation needed] However some people take pride in being a pedant, especially with regard to the use of the English language.[citation needed] In an attempt to avoid censure, people who wish to make a correction might preface it with "not wishing to be pedantic, but ..." or "without being a pedant, ...".[citation needed] Pedantry can also be an indication of certain developmental disorders. In particular those with high-functioning autism, often have behavior characterized by pedantic speech.[2] Those with Asperger's tend to obsess over the minutiae of subjects, and are prone to giving long detailed expositions, and the related corrections, and may gravitate to careers in academia or science where such obsessive attention to detail is often functional and rewarded. # Obsessive-compulsive personality disorder Obsessive-compulsive personality disorder is also in part characterized by a form of pedantry that is overly concerned with the correct following of rules, procedures and practices.[3] Sometimes the rules that OCPD sufferers obsessively follow are of their own devising, or are corruptions or re-interpretations of the letter of actual rules. # Quotations Template:Copy section to Wikiquote - "A Man who has been brought up among Books, and is able to talk of nothing else, is what we call a Pedant. But, methinks, we should enlarge the Title, and give it to every one that does not know how to think out of his Profession and particular way of Life." - Addison, Spectator 1711. [1] - "Nothing is as peevish and pedantic as men's judgments of one another." - Desiderius Erasmus [2] - "The pedant is he who finds it impossible to read criticism of himself, without immediately reaching for his pen and replying to the effect that the accusation is a gross insult to his person. He is, in effect, a man unable to laugh at himself." - Sigmund Freud, The Ego and the Id. - "Servile and impertinent, shallow and pedantic, a bigot and sot" - Thomas Macaulay, describing James Boswell - "The term, then, is obviously a relative one: my pedantry is your scholarship, his reasonable accuracy, her irreducible minimum of education and someone else’s ignorance." H. W. Fowler, Modern English Usage - "It's not pedantry, but merely a desire for accuracy." - Roy Cropper, in an episode of Coronation Street. - "Pedantic, I?" - Alexei Sayle - "The only other thing is that I am a pendant went it comes to written English and I would like to proof-read anything that can viewed outside the company." - Garty Vicksters - "He can be pedantic, he can be pedantic." - George Costanza, in The Big Salad episode of Seinfeld - "I find this meatloaf rather shallow and pedantic." - Peter Griffin, in Petarted episode of Family Guy	https://www.wikidoc.org/index.php/Pedant
db43e0a876142a2239064968436d011f435e616d	wikidoc	Pepsin	Pepsin Pepsin is an endopeptidase that breaks down proteins into smaller peptides (that is, a protease). It is produced in the stomach and is one of the main digestive enzymes in the digestive systems of humans and many other animals, where it helps digest the proteins in food. Pepsin has a three-dimensional structure, of which one or more polypeptide chains twist and fold, bringing together a small number of amino acids to form the active site, or the location on the enzyme where the substrate binds and the reaction takes place. Pepsin is an aspartic protease, using a catalytic aspartate in its active site. It is one of three principal proteases in the human digestive system, the other two being chymotrypsin and trypsin. During the process of digestion, these enzymes, each of which is specialized in severing links between particular types of amino acids, collaborate to break down dietary proteins into their components, i.e., peptides and amino acids, which can be readily absorbed by the small intestine. Pepsin is most efficient in cleaving peptide bonds between hydrophobic and preferably aromatic amino acids such as phenylalanine, tryptophan, and tyrosine. Pepsin's proenzyme, pepsinogen, is released by the chief cells in the stomach wall, and upon mixing with the hydrochloric acid of the gastric juice, pepsinogen activates to become pepsin. # History Pepsin was one of the first enzymes to be discovered, and is polypeptidic in nature. It was discovered in 1836 by Theodor Schwann. Schwann coined its name from the Greek word πέψις pepsis, meaning "digestion" (from πέπτειν peptein "to digest"). Scientists around this time began discovering many biochemical compounds that play a significant role in biological processes, and pepsin was one of them. An acidic substance that was able to convert nitrogen-based foods into water-soluble material was determined to be pepsin. In 1928, it became one of the first enzymes to be crystallized when John H. Northrop crystallized it using dialysis, filtration, and cooling. # Precursor Pepsin is expressed as a zymogen called pepsinogen, whose primary structure has an additional 44 amino acids. In the stomach, chief cells release pepsinogen. This zymogen is activated by hydrochloric acid (HCl), which is released from parietal cells in the stomach lining. The hormone gastrin and the vagus nerve trigger the release of both pepsinogen and HCl from the stomach lining when food is ingested. Hydrochloric acid creates an acidic environment, which allows pepsinogen to unfold and cleave itself in an autocatalytic fashion, thereby generating pepsin (the active form). Pepsin cleaves the 44 amino acids from pepsinogen to create more pepsin. # Activity and stability Pepsin is most active in acidic environments between 37 °C and 42 °C. Accordingly, its primary site of synthesis and activity is in the stomach (pH 1.5 to 2). Pepsin will digest up to 20% of ingested amide bonds by cleaving preferentially at the C-terminal side:96 of aromatic amino acids such as phenylalanine, tryptophan, and tyrosine.:675 Pepsin exhibits preferential cleavage for hydrophobic, preferably aromatic, residues in P1 and P1' positions. Increased susceptibility to hydrolysis occurs if there is a sulfur-containing amino acid close to the peptide bond, which has an aromatic amino acid. Pepsin cleaves Phe1Val, Gln4His, Glu13Ala, Ala14Leu, Leu15Tyr, Tyr16Leu, Gly23Phe, Phe24 in the insulin B chain. Pepsin exhibits maximal activity at pH 2.0 and is inactive at pH 6.5 and above, however pepsin is not fully denatured or irreversibly inactivated until pH 8.0. Therefore, pepsin in solution of up to pH 8.0 can be reactivated upon re-acidification. The stability of pepsin at high pH has significant implications on disease attributed to laryngopharyngeal reflux. Pepsin remains in the larynx following a gastric reflux event. At the mean pH of the laryngopharynx (pH = 6.8) pepsin would be inactive but could be reactivated upon subsequent acid reflux events resulting in damage to local tissues. # In laryngopharyngeal reflux Pepsin is one of the primary causes of mucosal damage during laryngopharyngeal reflux. Pepsin remains in the larynx (pH 6.8) following a gastric reflux event. While enzymatically inactive in this environment, pepsin would remain stable and could be reactivated upon subsequent acid reflux events. Exposure of laryngeal mucosa to enzymatically active pepsin, but not irreversibly inactivated pepsin or acid, results in reduced expression of protective proteins and thereby increases laryngeal susceptibility to damage. Pepsin may also cause mucosal damage during weakly acidic or non-acid gastric reflux. Weak or non-acid reflux is correlated with reflux symptoms and mucosal injury. Under non-acid conditions (neutral pH), pepsin is internalized by cells of the upper airways such as the larynx and hypopharynx by a process known as receptor-mediated endocytosis. The receptor by which pepsin is endocytosed is currently unknown. Upon cellular uptake, pepsin is stored in intracellular vesicles of low pH at which its enzymatic activity would be restored. Pepsin is retained within the cell for up to 24 hours. Such exposure to pepsin at neutral pH and endocyctosis of pepsin causes changes in gene expression associated with inflammation, which underlies signs and symptoms of reflux, and tumor progression. This and other research implicates pepsin in carcinogenesis attributed to gastric reflux. Pepsin in airway specimens is considered to be a sensitive and specific marker for laryngopharyngeal reflux. Research to develop new pepsin-targeted therapeutic and diagnostic tools for gastric reflux is ongoing. A rapid non-invasive pepsin diagnostic called Peptest is now available which determines the presence of pepsin in saliva samples. # Storage Pepsins should be stored at very low temperatures (between −80 °C and −20 °C) to prevent autolysis (self-digestion). # Inhibitors Pepsin may be inhibited by high pH (see "Activity" and "Stability", above) or by inhibitor compounds. Pepstatin is a low molecular weight compound and potent inhibitor specific for acid proteases with a Ki of about 10−10 M for pepsin. The statyl residue of pepstatin is thought to be responsible for pepstatin inhibition of pepsin; statine is a potential analog of the transition state for catalysis by pepsin and other acid proteases. Pepstatin does not covalently bind pepsin and inhibition of pepsin by pepstatin is therefore reversible. 1-bis(diazoacetyl)-2-phenylethane reversibly inactivates pepsin at pH 5, a reaction which is accelerated by the presence of Cu(II). Pepsin also undergoes feedback inhibition; a product of protein digestion slows down the reaction by inhibiting pepsin. Sucralfate also inhibits pepsin activity. # Applications Commercial pepsin is extracted from the glandular layer of hog stomachs. It is a component of rennet used to curdle milk during the manufacture of cheese. Pepsin is used for a variety of applications in food manufacturing: to modify and provide whipping qualities to soy protein and gelatin, to modify vegetable proteins for use in nondairy snack items, to make precooked cereals into instant hot cereals, and to prepare animal and vegetable protein hydrolysates for use in flavoring foods and beverages. It is used in the leather industry to remove hair and residual tissue from hides and in the recovery of silver from discarded photographic films by digesting the gelatin layer that holds the silver. Pepsin was historically an additive of Beemans gum brand chewing gum by Dr. Edward E. Beeman. Pepsin is commonly used in the preparation of F(ab')2 fragments from antibodies. In some assays, it is preferable to use only the antigen-binding (Fab) portion of the antibody. For these applications, antibodies may be enzymatically digested to produce either an Fab or an F(ab')2 fragment of the antibody. To produce an F(ab')2 fragment, IgG is digested with pepsin, which cleaves the heavy chains near the hinge region. One or more of the disulfide bonds that join the heavy chains in the hinge region are preserved, so the two Fab regions of the antibody remain joined together, yielding a divalent molecule (containing two antibody binding sites), hence the designation F(ab')2. The light chains remain intact and attached to the heavy chain. The Fc fragment is digested into small peptides. Fab fragments are generated by cleavage of IgG with papain instead of pepsin. Papain cleaves IgG above the hinge region containing the disulfide bonds that join the heavy chains, but below the site of the disulfide bond between the light chain and heavy chain. This generates two separate monovalent (containing a single antibody binding site) Fab fragments and an intact Fc fragment. The fragments can be purified by gel filtration, ion exchange, or affinity chromatography. Fab and F(ab')2 antibody fragments are used in assay systems where the presence of the Fc region may cause problems. In tissues such as lymph nodes or spleen, or in peripheral blood preparations, cells with Fc receptors (macrophages, monocytes, B lymphocytes, and natural killer cells) are present which can bind the Fc region of intact antibodies, causing background staining in areas that do not contain the target antigen. Use of F(ab')2 or Fab fragments ensures that the antibodies are binding to the antigen and not Fc receptors. These fragments may also be desirable for staining cell preparations in the presence of plasma, because they are not able to bind complement, which could lyse the cells. F(ab')2, and to a greater extent Fab, fragments allow more exact localization of the target antigen, i.e., in staining tissue for electron microscopy. The divalency of the F(ab')2 fragment enables it to cross-link antigens, allowing use for precipitation assays, cellular aggregation via surface antigens, or rosetting assays. # Genes The following three genes encode identical human pepsinogen A enzymes: A fourth human gene encodes gastricsin also known as pepsinogen C:	Pepsin Pepsin is an endopeptidase that breaks down proteins into smaller peptides (that is, a protease). It is produced in the stomach and is one of the main digestive enzymes in the digestive systems of humans and many other animals, where it helps digest the proteins in food. Pepsin has a three-dimensional structure, of which one or more polypeptide chains twist and fold, bringing together a small number of amino acids to form the active site, or the location on the enzyme where the substrate binds and the reaction takes place. Pepsin is an aspartic protease, using a catalytic aspartate in its active site.[2] It is one of three principal proteases in the human digestive system, the other two being chymotrypsin and trypsin. During the process of digestion, these enzymes, each of which is specialized in severing links between particular types of amino acids, collaborate to break down dietary proteins into their components, i.e., peptides and amino acids, which can be readily absorbed by the small intestine. Pepsin is most efficient in cleaving peptide bonds between hydrophobic and preferably aromatic amino acids such as phenylalanine, tryptophan, and tyrosine.[3] Pepsin's proenzyme, pepsinogen, is released by the chief cells in the stomach wall, and upon mixing with the hydrochloric acid of the gastric juice, pepsinogen activates to become pepsin.[2] # History Pepsin was one of the first enzymes to be discovered, and is polypeptidic in nature. It was discovered in 1836 by Theodor Schwann. Schwann coined its name from the Greek word πέψις pepsis, meaning "digestion" (from πέπτειν peptein "to digest").[4][5][6][7] Scientists around this time began discovering many biochemical compounds that play a significant role in biological processes, and pepsin was one of them. An acidic substance that was able to convert nitrogen-based foods into water-soluble material was determined to be pepsin.[8] In 1928, it became one of the first enzymes to be crystallized when John H. Northrop crystallized it using dialysis, filtration, and cooling.[9] # Precursor Pepsin is expressed as a zymogen called pepsinogen, whose primary structure has an additional 44 amino acids. In the stomach, chief cells release pepsinogen. This zymogen is activated by hydrochloric acid (HCl), which is released from parietal cells in the stomach lining. The hormone gastrin and the vagus nerve trigger the release of both pepsinogen and HCl from the stomach lining when food is ingested. Hydrochloric acid creates an acidic environment, which allows pepsinogen to unfold and cleave itself in an autocatalytic fashion, thereby generating pepsin (the active form). Pepsin cleaves the 44 amino acids from pepsinogen to create more pepsin. # Activity and stability Pepsin is most active in acidic environments between 37 °C and 42 °C.[10][11] Accordingly, its primary site of synthesis and activity is in the stomach (pH 1.5 to 2). Pepsin will digest up to 20% of ingested amide bonds by cleaving preferentially at the C-terminal side[12]:96 of aromatic amino acids such as phenylalanine, tryptophan, and tyrosine.[12]:675 Pepsin exhibits preferential cleavage for hydrophobic, preferably aromatic, residues in P1 and P1' positions. Increased susceptibility to hydrolysis occurs if there is a sulfur-containing amino acid close to the peptide bond, which has an aromatic amino acid. Pepsin cleaves Phe1Val, Gln4His, Glu13Ala, Ala14Leu, Leu15Tyr, Tyr16Leu, Gly23Phe, Phe24 in the insulin B chain. Pepsin exhibits maximal activity at pH 2.0 and is inactive at pH 6.5 and above, however pepsin is not fully denatured or irreversibly inactivated until pH 8.0.[13] Therefore, pepsin in solution of up to pH 8.0 can be reactivated upon re-acidification. The stability of pepsin at high pH has significant implications on disease attributed to laryngopharyngeal reflux. Pepsin remains in the larynx following a gastric reflux event.[14][15] At the mean pH of the laryngopharynx (pH = 6.8) pepsin would be inactive but could be reactivated upon subsequent acid reflux events resulting in damage to local tissues. # In laryngopharyngeal reflux Pepsin is one of the primary causes of mucosal damage during laryngopharyngeal reflux.[16][17] Pepsin remains in the larynx (pH 6.8) following a gastric reflux event.[14][15] While enzymatically inactive in this environment, pepsin would remain stable and could be reactivated upon subsequent acid reflux events.[13] Exposure of laryngeal mucosa to enzymatically active pepsin, but not irreversibly inactivated pepsin or acid, results in reduced expression of protective proteins and thereby increases laryngeal susceptibility to damage.[13][14][15] Pepsin may also cause mucosal damage during weakly acidic or non-acid gastric reflux. Weak or non-acid reflux is correlated with reflux symptoms and mucosal injury.[18][19][20][21] Under non-acid conditions (neutral pH), pepsin is internalized by cells of the upper airways such as the larynx and hypopharynx by a process known as receptor-mediated endocytosis.[22] The receptor by which pepsin is endocytosed is currently unknown. Upon cellular uptake, pepsin is stored in intracellular vesicles of low pH at which its enzymatic activity would be restored. Pepsin is retained within the cell for up to 24 hours.[23] Such exposure to pepsin at neutral pH and endocyctosis of pepsin causes changes in gene expression associated with inflammation, which underlies signs and symptoms of reflux,[24] and tumor progression.[25] This and other research[26] implicates pepsin in carcinogenesis attributed to gastric reflux. Pepsin in airway specimens is considered to be a sensitive and specific marker for laryngopharyngeal reflux.[27][28] Research to develop new pepsin-targeted therapeutic and diagnostic tools for gastric reflux is ongoing. A rapid non-invasive pepsin diagnostic called Peptest is now available which determines the presence of pepsin in saliva samples.[29] # Storage Pepsins should be stored at very low temperatures (between −80 °C and −20 °C) to prevent autolysis (self-digestion). # Inhibitors Pepsin may be inhibited by high pH (see "Activity" and "Stability", above) or by inhibitor compounds. Pepstatin is a low molecular weight compound and potent inhibitor specific for acid proteases with a Ki of about 10−10 M for pepsin. The statyl residue of pepstatin is thought to be responsible for pepstatin inhibition of pepsin; statine is a potential analog of the transition state for catalysis by pepsin and other acid proteases. Pepstatin does not covalently bind pepsin and inhibition of pepsin by pepstatin is therefore reversible.[30] 1-bis(diazoacetyl)-2-phenylethane reversibly inactivates pepsin at pH 5, a reaction which is accelerated by the presence of Cu(II).[31] Pepsin also undergoes feedback inhibition; a product of protein digestion slows down the reaction by inhibiting pepsin.[32][33] Sucralfate also inhibits pepsin activity. # Applications Commercial pepsin is extracted from the glandular layer of hog stomachs. It is a component of rennet used to curdle milk during the manufacture of cheese. Pepsin is used for a variety of applications in food manufacturing: to modify and provide whipping qualities to soy protein and gelatin,[34] to modify vegetable proteins for use in nondairy snack items, to make precooked cereals into instant hot cereals,[35] and to prepare animal and vegetable protein hydrolysates for use in flavoring foods and beverages. It is used in the leather industry to remove hair and residual tissue from hides and in the recovery of silver from discarded photographic films by digesting the gelatin layer that holds the silver.[36] Pepsin was historically an additive of Beemans gum brand chewing gum by Dr. Edward E. Beeman. Pepsin is commonly used in the preparation of F(ab')2 fragments from antibodies. In some assays, it is preferable to use only the antigen-binding (Fab) portion of the antibody. For these applications, antibodies may be enzymatically digested to produce either an Fab or an F(ab')2 fragment of the antibody. To produce an F(ab')2 fragment, IgG is digested with pepsin, which cleaves the heavy chains near the hinge region.[37] One or more of the disulfide bonds that join the heavy chains in the hinge region are preserved, so the two Fab regions of the antibody remain joined together, yielding a divalent molecule (containing two antibody binding sites), hence the designation F(ab')2. The light chains remain intact and attached to the heavy chain. The Fc fragment is digested into small peptides. Fab fragments are generated by cleavage of IgG with papain instead of pepsin. Papain cleaves IgG above the hinge region containing the disulfide bonds that join the heavy chains, but below the site of the disulfide bond between the light chain and heavy chain. This generates two separate monovalent (containing a single antibody binding site) Fab fragments and an intact Fc fragment. The fragments can be purified by gel filtration, ion exchange, or affinity chromatography.[38] Fab and F(ab')2 antibody fragments are used in assay systems where the presence of the Fc region may cause problems. In tissues such as lymph nodes or spleen, or in peripheral blood preparations, cells with Fc receptors (macrophages, monocytes, B lymphocytes, and natural killer cells) are present which can bind the Fc region of intact antibodies, causing background staining in areas that do not contain the target antigen. Use of F(ab')2 or Fab fragments ensures that the antibodies are binding to the antigen and not Fc receptors. These fragments may also be desirable for staining cell preparations in the presence of plasma, because they are not able to bind complement, which could lyse the cells. F(ab')2, and to a greater extent Fab, fragments allow more exact localization of the target antigen, i.e., in staining tissue for electron microscopy. The divalency of the F(ab')2 fragment enables it to cross-link antigens, allowing use for precipitation assays, cellular aggregation via surface antigens, or rosetting assays.[39] # Genes The following three genes encode identical human pepsinogen A enzymes: A fourth human gene encodes gastricsin also known as pepsinogen C:	https://www.wikidoc.org/index.php/Pepsin
9af88f688c89ccc93ba6c11026a56eefa7fb44b8	wikidoc	Peptic	Peptic # Overview Peptic is an adjective that refers to any part of the body that normally has an acidic lumen. 'Peptic' is medical and veterinary terminology, most often used in the context of humans. # Peptic anatomy The peptic areas of the human body under normal circumstances are the stomach and duodenum. A person with gastroesophageal reflux disease may have an acidic esophagus, particularly at the inferior (lower) end. Also, a person with a Meckel's diverticulum may have cells that produce acid within the diverticulum and therefore may be prone to peptic ulcers and perforation. A person with an unusual anatomy, such as one who has had a gastrectomy or an esophagectomy with transplantation of the ileum to replace the esophagus, may experience acidity in parts of the body that would not normally be acidic. In all normal humans and in almost all humans, only the gastrointestinal tract is peptic. # Peptic diseases A common problem with the peptic areas of the body is peptic ulcer. These ulcers are most commonly caused by bacteria, and not by the acidic environment.	Peptic # Overview Peptic is an adjective that refers to any part of the body that normally has an acidic lumen. 'Peptic' is medical and veterinary terminology, most often used in the context of humans. # Peptic anatomy The peptic areas of the human body under normal circumstances are the stomach and duodenum. A person with gastroesophageal reflux disease may have an acidic esophagus, particularly at the inferior (lower) end. Also, a person with a Meckel's diverticulum may have cells that produce acid within the diverticulum and therefore may be prone to peptic ulcers and perforation. A person with an unusual anatomy, such as one who has had a gastrectomy or an esophagectomy with transplantation of the ileum to replace the esophagus, may experience acidity in parts of the body that would not normally be acidic. In all normal humans and in almost all humans, only the gastrointestinal tract is peptic. # Peptic diseases A common problem with the peptic areas of the body is peptic ulcer. These ulcers are most commonly caused by bacteria, and not by the acidic environment. Template:WH Template:WikiDoc Sources	https://www.wikidoc.org/index.php/Peptic
90cc827af3ba8a81abda7652305727d0d4509c2e	wikidoc	Rectum	Rectum # Overview The rectum (from the Latin rectum intestinum, meaning straight intestine) is the final straight portion of the large intestine in some mammals, and the gut in others, terminating in the anus. The human rectum is about 12 cm long. At its commencement its caliber is similar to that of the sigmoid colon, but near its termination it is dilated, forming the rectal ampulla. # Role in human defecation The rectum intestinum acts as a temporary storage facility for feces. As the rectal walls expand due to the materials filling it from within, stretch receptors from the nervous system located in the rectal walls stimulate the desire to defecate. If the urge is not acted upon, the material in the rectum is often returned to the colon where more water is absorbed. If defecation is delayed for a prolonged period, constipation and hardened feces results. When the rectum becomes full the increase in intrarectal pressure forces the walls of the anal canal apart allowing the fecal matter to enter the canal. The rectum shortens as material is forced into the anal canal and peristaltic waves propel the feces out of the rectum. The internal and external sphincter allow the faeces to be passed by muscles pulling the anus up over the exiting faeces. # Medical procedures For the diagnosis of certain ailments, a rectal exam may be done. Suppositories may be inserted into the rectum as a route of administration for medicine. The endoscopic procedures colonoscopy and sigmoidoscopy are performed to diagnose diseases such as cancer. ## Temperature taking Body temperature can also be taken in the rectum. Rectal temperature can be taken by inserting a mercury thermometer for 3 to 5 minutes, or a digital thermometer until it "beeps", not more than 25 mm (1 inch) into the rectum via the anus. Due to recent concerns related to mercury poisoning, the use of mercury thermometers is now discouraged. Normal rectal temperature generally ranges from 36 to 38 °C (97.6 to 100.4 °F) and is about 0.5 °C (1 °F) above oral (mouth) temperature and about 1 °C (2 °F) above axillary (armpit) temperature. Many pediatricians recommend that parents take infants and toddler's temperature in the rectum for two reasons: - (1) Rectal temperature is the closest to core body temperature and in children that young, accuracy is critical. - (2) Younger children are unable to cooperate when having their temperature taken by mouth (oral) which is recommended for children, ages 6 and above and for adults. In recent years, the introduction of ear (tympanic) thermometers and changing attitudes on privacy and modesty have led some parents and doctors to discontinue taking rectal temperatures. # Sexual stimulation Due to the proximity of the anterior wall of the rectum to the vagina in females or to the prostate in males and the shared nerves thereof, rectal stimulation or penetration can result in sexual arousal. For further information on this aspect, see anal sex. # Additional images - Organs of the female reproductive system. - Median sagittal section of pelvis, showing arrangement of fasciæ. - The arteries of the pelvis. - Section of mucous membrane of human rectum. X 60. - The blood vessels of the rectum and anus. - Median sagittal section of male pelvis. - Median sagittal section of female pelvis. - Sagittal section of the lower part of a female trunk, right segment. - Error creating thumbnail: File missing The rectum can be seen the left of this illustration. - Cross section microscopic shot of the rectal wall.	Rectum Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] # Overview Template:Infobox Anatomy The rectum (from the Latin rectum intestinum, meaning straight intestine) is the final straight portion of the large intestine in some mammals, and the gut in others, terminating in the anus. The human rectum is about 12 cm long. At its commencement its caliber is similar to that of the sigmoid colon, but near its termination it is dilated, forming the rectal ampulla. # Role in human defecation The rectum intestinum acts as a temporary storage facility for feces. As the rectal walls expand due to the materials filling it from within, stretch receptors from the nervous system located in the rectal walls stimulate the desire to defecate. If the urge is not acted upon, the material in the rectum is often returned to the colon where more water is absorbed. If defecation is delayed for a prolonged period, constipation and hardened feces results. When the rectum becomes full the increase in intrarectal pressure forces the walls of the anal canal apart allowing the fecal matter to enter the canal. The rectum shortens as material is forced into the anal canal and peristaltic waves propel the feces out of the rectum. The internal and external sphincter allow the faeces to be passed by muscles pulling the anus up over the exiting faeces. # Medical procedures For the diagnosis of certain ailments, a rectal exam may be done. Suppositories may be inserted into the rectum as a route of administration for medicine. The endoscopic procedures colonoscopy and sigmoidoscopy are performed to diagnose diseases such as cancer. ## Temperature taking Body temperature can also be taken in the rectum. Rectal temperature can be taken by inserting a mercury thermometer for 3 to 5 minutes, or a digital thermometer until it "beeps", not more than 25 mm (1 inch) into the rectum via the anus. Due to recent concerns related to mercury poisoning, the use of mercury thermometers is now discouraged. Normal rectal temperature generally ranges from 36 to 38 °C (97.6 to 100.4 °F) and is about 0.5 °C (1 °F) above oral (mouth) temperature and about 1 °C (2 °F) above axillary (armpit) temperature. Many pediatricians recommend that parents take infants and toddler's temperature in the rectum for two reasons: - (1) Rectal temperature is the closest to core body temperature and in children that young, accuracy is critical. - (2) Younger children are unable to cooperate when having their temperature taken by mouth (oral) which is recommended for children, ages 6 and above and for adults. In recent years, the introduction of ear (tympanic) thermometers and changing attitudes on privacy and modesty have led some parents and doctors to discontinue taking rectal temperatures. # Sexual stimulation Due to the proximity of the anterior wall of the rectum to the vagina in females or to the prostate in males and the shared nerves thereof, rectal stimulation or penetration can result in sexual arousal. For further information on this aspect, see anal sex. # Additional images - Organs of the female reproductive system. - Median sagittal section of pelvis, showing arrangement of fasciæ. - The arteries of the pelvis. - Section of mucous membrane of human rectum. X 60. - The blood vessels of the rectum and anus. - Median sagittal section of male pelvis. - Median sagittal section of female pelvis. - Sagittal section of the lower part of a female trunk, right segment. - Error creating thumbnail: File missing The rectum can be seen the left of this illustration. - Cross section microscopic shot of the rectal wall.	https://www.wikidoc.org/index.php/Perirectal
110c6b60dcccd3e0528c4bbfc03f7c1087b32846	wikidoc	Persin	Persin Persin is a fungicidal toxin present in the avocado, isolated only recently. It is generally harmless to humans, but when consumed by domestic animals in large quantities it is dangerous. It has been suggested as a treatment for breast cancer. The chemistry of persin is not yet understood, but it is similar to a fatty acid, carried in an oil, and it leaches into the body of the fruit from the pits. Negative effects in humans seem to be primarily in allergic individuals. # Pathology Feeding avocados or guacamole to any non-human animal should be avoided completely. The symptoms include gastrointestinal irritation, vomiting, diarrhea, respiratory distress, congestion, fluid accumulation around the tissues of the heart and even death. Birds seem to be particularly sensitive to this toxic compound. Pits may lodge in the intestinal tract of cats and dogs and require surgery for removal. - In birds, the symptoms are: increased heart rate, myocardial tissue damage, labored breathing, disordered plumage, unrest, weakness, and apathy. High doses cause acute respiratory syndrome (asphyxia), with death approximately 12 to 24 hours after consumption. - Lactating rabbits and mice: non-infectious mastitis and agalactia after consumption of leaves or bark. - Rabbits: cardial arrhythmia, submandibular edema and death after consumption of leaves. - Cows and goats: mastitis after consumption of leaves or bark. - Horses: mastitis after consumption of leaves or bark. - Hares, pigs, rats, sheep, ostriches, chickens, turkeys and fish: symptoms of intoxication similar those described above. The lethal dose is not known; the effect is different depending upon the animal species. # Medical uses Persin has recently been discovered to kill breast cancer cells. It has also been shown to enhance the effect of the breast cancer fighting drug Tamoxifen. This could potentially reduce the necessary dosage of current cancer drugs. Persin is however highly insoluble, and more research will be needed to put it into a soluble tablet form. The result was announced by the Garvan Institute at the Australian Society for Medical Research meeting held at the Powerhouse Museum, Ultimo, on 4 June 2007.	Persin Persin is a fungicidal toxin present in the avocado, isolated only recently.[1] It is generally harmless to humans, but when consumed by domestic animals in large quantities it is dangerous. It has been suggested as a treatment for breast cancer.[2] The chemistry of persin is not yet understood, but it is similar to a fatty acid, carried in an oil, and it leaches into the body of the fruit from the pits. Negative effects in humans seem to be primarily in allergic individuals. # Pathology Feeding avocados or guacamole to any non-human animal should be avoided completely. The symptoms include gastrointestinal irritation, vomiting, diarrhea, respiratory distress, congestion, fluid accumulation around the tissues of the heart and even death. Birds seem to be particularly sensitive to this toxic compound. Pits may lodge in the intestinal tract of cats and dogs and require surgery for removal. - In birds, the symptoms are: increased heart rate, myocardial tissue damage, labored breathing, disordered plumage, unrest, weakness, and apathy. High doses cause acute respiratory syndrome (asphyxia), with death approximately 12 to 24 hours after consumption. - Lactating rabbits and mice: non-infectious mastitis and agalactia after consumption of leaves or bark. - Rabbits: cardial arrhythmia, submandibular edema and death after consumption of leaves. - Cows and goats: mastitis after consumption of leaves or bark. - Horses: mastitis after consumption of leaves or bark. - Hares, pigs, rats, sheep, ostriches, chickens, turkeys and fish: symptoms of intoxication similar those described above. The lethal dose is not known; the effect is different depending upon the animal species.[3][4] # Medical uses Persin has recently been discovered to kill breast cancer cells. It has also been shown to enhance the effect of the breast cancer fighting drug Tamoxifen. This could potentially reduce the necessary dosage of current cancer drugs. Persin is however highly insoluble, and more research will be needed to put it into a soluble tablet form. The result was announced by the Garvan Institute at the Australian Society for Medical Research meeting held at the Powerhouse Museum, Ultimo, on 4 June 2007.[5]	https://www.wikidoc.org/index.php/Persin
84b60362849afbf34b59928c67555f9db03c8264	wikidoc	Person	Person The classical definition of a person is "a human being regarded as an individual." In modern usage, the term "person" is subject to dispute and re-interpretation based on alternate definitions. This is especially so for uses that are not necessarily synonymous with the classical definition of human or human being. For example, in many jurisdictions a corporation may be treated as a "person" under the law. In the fields of philosophy, theology, and bioethics, the definition of 'person' may exclude human beings who are incapable of certain kinds of thought (such as embryos, fetuses with incomplete brain development, or adult humans lacking higher brain functions). These alternative definitions of what constitutes a "person" include a wide and varying range of alternative defining characteristics, some of which have evolved historically, and continue to shift with time and social context. Some other characteristics used to define a 'person' include personal identity, self-awareness, individuality, and a sense of self that persists through time. Other views centre around the degree to which properties such as agency (both human agency and moral agency) and rights are recognized and acknowledged in society or enforcable by law. The recognition of status as a person is known as personhood. The inquiry into what it means to be a 'person' is the subject of considerable analysis and debate within diverse fields such as religion, medicine, ethics, economic and political theory, human rights, and animal rights. # Overview The establishment of 'personhood' represents a complex issue that covers a wide swath of human activities and discourse. Generally, the issue can be categorized by the underlying intended uses of the term "person". Such intended uses include: - Analytic: definitions or prescriptive rules used to delineate personhood in a falsifiable formal system; - Normative: moral or deontological arguments to advocate fair and equitable treatment for recognized classes of sentient beings; - Conceptual: descriptive, taxonomical, or epistemological inquiry into the fundamental nature, limitations, and scope of personhood; especially as it relates to the examination of living organisms or other intelligences; - Metaphysical: esoteric or mystical exposition of personhood; especially as it relates to religion, spirituality, or mythical views and beliefs outside ordinary human experience - Artistic: literary, rhetorical or allegorical devices to convey personhood; especially as it relates to fantasy and science fiction Discourse on personhood may combine different elements of the previous categories in order to coincide with a particular viewpoint or academic theory. For example, a legal scholar and economist might define a person as "any being with the neurological prerequisites to understand moral consequences and take his life morally seriously." (Markovits) The conceptual and normative elements could then be incorporated into established legal doctrine and economic theory, both of which assume some level of individual choice and personal responsibility. The normative principle of absolutism is often combined with an analytic definition of persons as co-equal participants in a given society, based on citizenship, nationality or common humanity. This combination is very common in such instruments as the Declaration of the Rights of Man and of the Citizen, and the Universal Declaration of Human Rights. ## Analytic definitions A person can have recognition, existence and legal capacity under the law (legal personhood). There are various legally operative definitions for personhood, but they all rely on formal, prescriptive definitions that must eventually be evaluated and falsifiable. Most such definitions form the basis of specific rights that may be exercised or enforced (such as human rights, custody, conservatorship and suffrage). Such definitions may also impose obligations or duties which carry a penalty if they are breached. Some legally operative definitions of 'person' go beyond the scope of establishing rights and obligations for individual human beings. For example, in many jurisdictions, any artificial legal entity (like a school, business, or non-profit organization) is considered a juristic person. As another example, the United States Constitution has historically applied different definitions of 'person' for the purpose of allotting seats in the House of Representatives. ## Normative views Recognition as a 'person' is significant in society because it goes to the heart of many debates over the status, respect, rights, and treatments, which are obligatory to different types of living beings. It is closely connected to the societal concept that sufficiently intelligent or self-aware beings should be respected and have their rights enforced for this reason, whereas a degree of exploitation is permissible for entities lacking it. Such exploitation has at times taken the form of slavery or medical torture for humans, and cruelty and vivisection for animals. Personhood is directly connected to issues such as rights and the capability to protect those rights by law or to have them protected on one's behalf if incapable. ## Conceptual views Human beings represent the most prevalent conceptual definition of 'person'. Some philosophers, like Peter Singer of Princeton University, regard certain types of animals with high cognitive abilities and a degree of societal development as persons, and argue that some human beings — for example, those with certain types of brain damage — are not. Should other intelligent life ever be discovered beyond those known to science, similar questions would be relevant in establishing personhood. ## Metaphysical views Personhood is held by some to be an attribute of more than just human beings. Some religions specify deities as occupying the place of personhood in many different forms. It is not uncommon for spiritual and archetypal roles to be depicted as "persons". For example, in the Book of Proverbs the attribute Wisdom is personified: Scripture scholars differ on whether and the extent to which this and other similar personification represents an attribute of the Divine Nature as made manifest in the form of a distinct 'person'. ## Artistic depictions Personhood is frequently examined through any of several artistic modalities, especially in literary works. In fictional works, fantasy and science fiction often explore the question of personhood by relaxing one or more of the common characteristics associated with it, and then exploring the ramifications and possible consequences. For example, Isaac Asimov introduced the three laws of robotics by relaxing the assumption that personhood is restricted to biological organisms. As another example, David Brin explored the attributes of personhood; especially identity, autonomy, and agency, by depicting a world in which characters could "copy" themselves in the novel Kiln People. An notable example if the character Data from Star Trek: The Next Generation. In one episode Data's status as a legal person was question and a hearing was carried out to determine if Data, an android who lacked human emotions but otherwise met or exceeded all other human mental characteristics such as self-awareness, imagination, creativity etc qualified as a person. # Personhood in philosophy and theory Philosophers have expounded on every dimension — from the purely analytical to the metaphysical — in discourses on personhood. Conceptually, a person is defined by the characteristics of reasoning, consciousness, and persistent personal identity. The English philosopher John Locke defined a person as "a thinking intelligent Being, that has reason and reflection, and can consider it self as it self, the same thinking thing in different times and places; which it does only by that consciousness, which is inseparable from thinking, and as it seems to me essential to it" (Essay on Humane Understanding, Book 2, Chapter 27, Section 9). ## Personhood theory According to Boethius: John Locke emphasized the idea of a living being that is conscious of itself as persisting over time (and hence able to have conscious preferences about its own future). In recent years a kind of consensus among secular scholars has emerged, which might be referred to as "personhood theory". This is strongly influenced by Locke's approach. The criteria a person must have in being a person are one or more of the following: - Consciousness, - The ability to steer one's attention and action purposively, - Self-awareness, self-bonded to objectivities (existing independently of the subject's perception of it), - Self as longitudinal thematic identity, one's biographic identity. Neo-Kantian philosophers over the last two decades have emphasized that conscious awareness requires both: - The sensorial capacity to access an environment (and one's own body) in a way that offers the basic qualitative content for subjective experience. - The intellectual capacity to conceptually interpret sensorial content as representing some thing to oneself. Both of these capacities are required for a subject of experience, action, thought, or self-reflection to exist, at least in the physically embodied, world-accessing manner of humans (and presumably other intelligent animals). As Kant wrote: Without sensibility no object would be given to us, and without understanding none would be thought. Thoughts without content are empty, intuitions without concepts are blind. (Critique of Pure Reason, A 51 = B 75). For those who consider an embodied capacity for subjectivity as necessary for personhood, these abstract constraints are quite relevant to the personhood theory debate. Advocates of alternative positions, such as a biological species or potentiality criterion, would instead need to provide arguments against embodied subjectivity as a basis for personhood. For example, one might argue that property claims are made by immaterial minds on immature material bodies, though any claim as to the nature of such minds would be necessarily speculative and would typically involve an argument for Cartesian substance dualism (see "mind-body problem"). In addition speculatively, there are three other likely categories of beings where personhood might be at issue: - Unknown intelligent life-forms - for example, should alien life be found to exist, under what circumstances would they be counted as 'persons'? - Artificial life - at what point might human-created life be considered to have achieved 'personhood'? - Artificial intelligence - assuming the eventual creation of an intelligent and self-aware system of hardware and software, what criteria would be used to confer or withhold the status of 'person'? - Modified living beings - for example, how much of a human being can be replaced by artificial parts before personhood is lost? - Further, if the brain is the reason people are considered 'persons', then if the human brain and all its thought patterns, memories and other attributes could also in future be transposed faithfully into some form of artificial device (for example to avoid illness such as brain cancer) would the patient still be considered a 'person' after the operation? Such questions are used by philosophers to clarify thinking concerning what it means to be 'human', or 'living', or a 'person'. # Implications of the person, non-person debate The personhood theory has become a pivotal issue in the interdisciplinary field of bioethics. While historically most humans did not enjoy full legal protection as "persons" (women, children, non-landowners, minorities, slaves, etc.), from the late 18th through the late 20th century being born as a member of the human species gradually became secular grounds for an appeal for basic rights of liberty, freedom from persecution, and humanitarian care. Since modern movements emerged to oppose animal cruelty (and advocate vegetarian or vegan lifestyles) and theorists like Turing have recognized the possibility of artificial minds with human-level competence, the identification of personhood protections exclusively with human species membership has been challenged. On the other hand, some proponents of "human exceptionalism" (also referred to by its critics as "speciesism") have countered that we must institute a strict demarcation of personhood based on species membership in order to avoid the horrors of genocide (based on propaganda dehumanizing one or more ethnicities) or the injustices of forced sterilization (as occurred in the U.S. to people with low I.Q. scores and prisoners). While the former advocates tend to be comfortable constraining personhood status within the human species based on basic capacities (e.g. excluding human stem cells, fetuses, and bodies that cannot recover awareness), the latter often wish to include all these forms of human bodies even if they have never had awareness (which some would call "pre-people") or had awareness, but could never have awareness again due to massive and irrecoverable brain damage (some would call these "post-people"). The Vatican has recently been advancing a human exceptionist understanding of the personhood theory, while other communities such as Christian Evangelicals in the U.S. have sometimes rejected the personhood theory as biased against human exceptionism. Of course, many religious communities (of many traditions) view the other versions of the personhood theory perfectly compatible with their faith, as do the majority of modern Humanists. The theoretical landscape of the personhood theory has been altered recently by controversy in the bioethics community concerning an emerging community of scholars, researchers and activists identifying with an explicitly Transhumanist position, which supports morphological freedom even if a person changed so much as to no longer be considered members of the human species (whatever standard is used for this determination). # Individual rights and responsibility Closely related to the debate on the definition of personhood is the relationship between persons', individual rights, and ethical responsibility. Many philosophers would agree that all and only people are expected to be ethically responsible, and that all people deserve a varying degree of individual rights. There is less consensus on whether only people deserve individual rights and whether people deserve greater individual rights than non-people. The rights of animals are an example of contention on this issue. # Nonhuman sentient beings as persons The idea of extending personhood to all animals has the support of legal scholars such as Alan Dershowitz and Laurence Tribe of Harvard Law School, and animal law courses are now taught in 92 out of 180 law schools in the United States. On May 9, 2008, Columbia University Press will publish Animals as Persons: Essays on the Abolition of Animal Exploitation by Prof. Gary L. Francione of Rutgers University School of Law, a collection of writings that summarizes his work to date and makes the case for non-human animals as persons. There are also hypothetical persons, sentient non-human persons such as sentient extra-terrestrial life and self aware machines. A popular Novel and loosely based animated series called Ghost in the Shell frequently touches on the potential of inorganic sentience, while classical works of fiction and fantasy regarding extra-terrestrials have challenged people to reconsider long held traditional definitions.	Person The classical definition of a person is "a human being regarded as an individual."[1] In modern usage, the term "person" is subject to dispute and re-interpretation based on alternate definitions. This is especially so for uses that are not necessarily synonymous with the classical definition of human or human being. For example, in many jurisdictions a corporation may be treated as a "person" under the law. In the fields of philosophy, theology, and bioethics, the definition of 'person' may exclude human beings who are incapable of certain kinds of thought (such as embryos, fetuses with incomplete brain development, or adult humans lacking higher brain functions).[2][3] These alternative definitions of what constitutes a "person" include a wide and varying range of alternative defining characteristics, some of which have evolved historically, and continue to shift with time and social context. Some other characteristics used to define a 'person' include personal identity,[4] self-awareness, individuality, and a sense of self that persists through time. Other views centre around the degree to which properties such as agency (both human agency and moral agency) and rights are recognized and acknowledged in society or enforcable by law. The recognition of status as a person is known as personhood. The inquiry into what it means to be a 'person' is the subject of considerable analysis and debate within diverse fields such as religion, medicine, ethics, economic and political theory, human rights, and animal rights. # Overview The establishment of 'personhood' represents a complex issue that covers a wide swath of human activities and discourse. Generally, the issue can be categorized by the underlying intended uses of the term "person". Such intended uses include: - Analytic: definitions or prescriptive rules used to delineate personhood in a falsifiable formal system; - Normative: moral or deontological arguments to advocate fair and equitable treatment for recognized classes of sentient beings; - Conceptual: descriptive, taxonomical, or epistemological inquiry into the fundamental nature, limitations, and scope of personhood; especially as it relates to the examination of living organisms or other intelligences; - Metaphysical: esoteric or mystical exposition of personhood; especially as it relates to religion, spirituality, or mythical views and beliefs outside ordinary human experience - Artistic: literary, rhetorical or allegorical devices to convey personhood; especially as it relates to fantasy and science fiction[5] Discourse on personhood may combine different elements of the previous categories in order to coincide with a particular viewpoint or academic theory. For example, a legal scholar and economist might define a person as "any being with the neurological prerequisites to understand moral consequences and take his life morally seriously." (Markovits) The conceptual and normative elements could then be incorporated into established legal doctrine and economic theory, both of which assume some level of individual choice and personal responsibility. The normative principle of absolutism is often combined with an analytic definition of persons as co-equal participants in a given society, based on citizenship, nationality or common humanity. This combination is very common in such instruments as the Declaration of the Rights of Man and of the Citizen, and the Universal Declaration of Human Rights. ## Analytic definitions A person can have recognition, existence and legal capacity under the law (legal personhood). There are various legally operative definitions for personhood, but they all rely on formal, prescriptive definitions that must eventually be evaluated and falsifiable. Most such definitions form the basis of specific rights that may be exercised or enforced (such as human rights, custody, conservatorship and suffrage). Such definitions may also impose obligations or duties which carry a penalty if they are breached. Some legally operative definitions of 'person' go beyond the scope of establishing rights and obligations for individual human beings. For example, in many jurisdictions, any artificial legal entity (like a school, business, or non-profit organization) is considered a juristic person. As another example, the United States Constitution has historically applied different definitions of 'person' for the purpose of allotting seats in the House of Representatives. ## Normative views Recognition as a 'person' is significant in society because it goes to the heart of many debates over the status, respect, rights, and treatments, which are obligatory to different types of living beings. It is closely connected to the societal concept that sufficiently intelligent or self-aware beings should be respected and have their rights enforced for this reason, whereas a degree of exploitation is permissible for entities lacking it. Such exploitation has at times taken the form of slavery or medical torture for humans, and cruelty and vivisection for animals. Personhood is directly connected to issues such as rights and the capability to protect those rights by law or to have them protected on one's behalf if incapable. ## Conceptual views Human beings represent the most prevalent conceptual definition of 'person'. Some philosophers, like Peter Singer of Princeton University, regard certain types of animals with high cognitive abilities and a degree of societal development as persons, and argue that some human beings — for example, those with certain types of brain damage — are not. Should other intelligent life ever be discovered beyond those known to science, similar questions would be relevant in establishing personhood. ## Metaphysical views Personhood is held by some to be an attribute of more than just human beings. Some religions specify deities as occupying the place of personhood in many different forms. It is not uncommon for spiritual and archetypal roles to be depicted as "persons". For example, in the Book of Proverbs the attribute Wisdom is personified: Scripture scholars differ on whether and the extent to which this and other similar personification represents an attribute of the Divine Nature as made manifest in the form of a distinct 'person'. ## Artistic depictions Personhood is frequently examined through any of several artistic modalities, especially in literary works. In fictional works, fantasy and science fiction often explore the question of personhood by relaxing one or more of the common characteristics associated with it, and then exploring the ramifications and possible consequences. For example, Isaac Asimov introduced the three laws of robotics by relaxing the assumption that personhood is restricted to biological organisms. As another example, David Brin explored the attributes of personhood; especially identity, autonomy, and agency, by depicting a world in which characters could "copy" themselves in the novel Kiln People.[5] An notable example if the character Data from Star Trek: The Next Generation. In one episode Data's status as a legal person was question and a hearing was carried out to determine if Data, an android who lacked human emotions but otherwise met or exceeded all other human mental characteristics such as self-awareness, imagination, creativity etc qualified as a person. # Personhood in philosophy and theory Philosophers have expounded on every dimension — from the purely analytical to the metaphysical — in discourses on personhood. Conceptually, a person is defined by the characteristics of reasoning, consciousness, and persistent personal identity. The English philosopher John Locke defined a person as "a thinking intelligent Being, that has reason and reflection, and can consider it self as it self, the same thinking thing in different times and places; which it does only by that consciousness, which is inseparable from thinking, and as it seems to me essential to it" (Essay on Humane Understanding, Book 2, Chapter 27, Section 9). ## Personhood theory According to Boethius: John Locke emphasized the idea of a living being that is conscious of itself as persisting over time (and hence able to have conscious preferences about its own future). In recent years a kind of consensus among secular scholars has emerged, which might be referred to as "personhood theory". This is strongly influenced by Locke's approach. The criteria a person must have in being a person are one or more of the following: - Consciousness, - The ability to steer one's attention and action purposively, - Self-awareness, self-bonded to objectivities (existing independently of the subject's perception of it), - Self as longitudinal thematic identity, one's biographic identity. Neo-Kantian philosophers over the last two decades have emphasized that conscious awareness requires both: - The sensorial capacity to access an environment (and one's own body) in a way that offers the basic qualitative content for subjective experience. - The intellectual capacity to conceptually interpret sensorial content as representing some thing to oneself. Both of these capacities are required for a subject of experience, action, thought, or self-reflection to exist, at least in the physically embodied, world-accessing manner of humans (and presumably other intelligent animals). As Kant wrote: Without sensibility no object would be given to us, and without understanding none would be thought. Thoughts without content are empty, intuitions without concepts are blind. (Critique of Pure Reason, A 51 = B 75). For those who consider an embodied capacity for subjectivity as necessary for personhood, these abstract constraints are quite relevant to the personhood theory debate. Advocates of alternative positions, such as a biological species or potentiality criterion, would instead need to provide arguments against embodied subjectivity as a basis for personhood. For example, one might argue that property claims are made by immaterial minds on immature material bodies, though any claim as to the nature of such minds would be necessarily speculative and would typically involve an argument for Cartesian substance dualism (see "mind-body problem"). In addition speculatively, there are three other likely categories of beings where personhood might be at issue: - Unknown intelligent life-forms - for example, should alien life be found to exist, under what circumstances would they be counted as 'persons'? - Artificial life - at what point might human-created life be considered to have achieved 'personhood'? - Artificial intelligence - assuming the eventual creation of an intelligent and self-aware system of hardware and software, what criteria would be used to confer or withhold the status of 'person'? - Modified living beings - for example, how much of a human being can be replaced by artificial parts before personhood is lost? - Further, if the brain is the reason people are considered 'persons', then if the human brain and all its thought patterns, memories and other attributes could also in future be transposed faithfully into some form of artificial device (for example to avoid illness such as brain cancer) would the patient still be considered a 'person' after the operation? Such questions are used by philosophers to clarify thinking concerning what it means to be 'human', or 'living', or a 'person'. # Implications of the person, non-person debate The personhood theory has become a pivotal issue in the interdisciplinary field of bioethics. While historically most humans did not enjoy full legal protection as "persons" (women, children, non-landowners, minorities, slaves, etc.), from the late 18th through the late 20th century being born as a member of the human species gradually became secular grounds for an appeal for basic rights of liberty, freedom from persecution, and humanitarian care. Since modern movements emerged to oppose animal cruelty (and advocate vegetarian or vegan lifestyles) and theorists like Turing have recognized the possibility of artificial minds with human-level competence, the identification of personhood protections exclusively with human species membership has been challenged. On the other hand, some proponents of "human exceptionalism" (also referred to by its critics as "speciesism") have countered that we must institute a strict demarcation of personhood based on species membership in order to avoid the horrors of genocide (based on propaganda dehumanizing one or more ethnicities) or the injustices of forced sterilization (as occurred in the U.S. to people with low I.Q. scores and prisoners). While the former advocates tend to be comfortable constraining personhood status within the human species based on basic capacities (e.g. excluding human stem cells, fetuses, and bodies that cannot recover awareness), the latter often wish to include all these forms of human bodies even if they have never had awareness (which some would call "pre-people") or had awareness, but could never have awareness again due to massive and irrecoverable brain damage (some would call these "post-people"). The Vatican has recently been advancing a human exceptionist understanding of the personhood theory, while other communities such as Christian Evangelicals in the U.S. have sometimes rejected the personhood theory as biased against human exceptionism. Of course, many religious communities (of many traditions) view the other versions of the personhood theory perfectly compatible with their faith, as do the majority of modern Humanists. The theoretical landscape of the personhood theory has been altered recently by controversy in the bioethics community concerning an emerging community of scholars, researchers and activists identifying with an explicitly Transhumanist position, which supports morphological freedom even if a person changed so much as to no longer be considered members of the human species (whatever standard is used for this determination). # Individual rights and responsibility Closely related to the debate on the definition of personhood is the relationship between persons', individual rights, and ethical responsibility. Many philosophers would agree that all and only people are expected to be ethically responsible, and that all people deserve a varying degree of individual rights. There is less consensus on whether only people deserve individual rights and whether people deserve greater individual rights than non-people. The rights of animals are an example of contention on this issue. # Nonhuman sentient beings as persons The idea of extending personhood to all animals has the support of legal scholars such as Alan Dershowitz[6] and Laurence Tribe of Harvard Law School,[7] and animal law courses are now taught in 92 out of 180 law schools in the United States.[8] On May 9, 2008, Columbia University Press will publish Animals as Persons: Essays on the Abolition of Animal Exploitation by Prof. Gary L. Francione of Rutgers University School of Law, a collection of writings that summarizes his work to date and makes the case for non-human animals as persons. There are also hypothetical persons, sentient non-human persons such as sentient extra-terrestrial life and self aware machines. A popular Novel and loosely based animated series called Ghost in the Shell frequently touches on the potential of inorganic sentience, while classical works of fiction and fantasy regarding extra-terrestrials have challenged people to reconsider long held traditional definitions.	https://www.wikidoc.org/index.php/Person
54e66f6c9481c2ad21e3b3a40bcc182a777e1f7d	wikidoc	Peyote	Peyote Lophophora williamsii, (lō-fof′ŏ-ră wil-yăm′sē-ī), better known by its common name Peyote, but also sometimes called Mescal Button or the Divine Cactus, is a small, spineless cactus whose native region extends from the southwestern United States, specifically in the southwestern part of Texas, through central Mexico. They are found primarily in the Chihuahuan desert and in the states of Tamaulipas and San Luis Potosi amongst scrub, especially when limestone is present in the soil. The cactus is well known for its psychoactive alkaloids and among these mescaline in particular. It is currently used world wide mainly as a recreational drug, an entheogen, and a tool in use to supplement various types of practices for transcendence including in meditation, psychonautics, and illegal psychedelic psychotherapy whether self administered or not. Certain American Indians tribes have used the plant for thousands of years prior to European arrival in the Americas, for both medicinal and religious purposes. The plant's pink flowers emerge from March through May, and in exceptional cases as late as September. # Description The cactus flowers sporadically, producing small pink fruit, which can be very delectable and bitter-sweet-tasting when eaten. The seeds are small and black, requiring hot and humid conditions to germinate. Peyote contains a large spectrum of phenethylamine alkaloids, the principal of which is mescaline. The mescaline content of Lophophora williamsii is about 0.4% fresh (undried) and 3-6% dried. All Lophophora species are extremely slow growing, often taking three years to reach flowering age in the wild (about the size of a golf ball, not including its root). Human cultivated specimens grow considerably faster, usually taking less than three years to go from seedling to mature flowering adult, and more rapid growth can be achieved by grafting Peyote onto mature San Pedro root stock; to expedite the age at which the Peyote flowers. Peyote contains two antibiotics named peyocactin. The top of the cactus that grows above ground, also referred to as the crown, consists of disc-shaped buttons that are cut above the roots and sometimes dried. When done properly, the top of the root will callous over, and new buttons will eventually grow from the root left in the ground. The cut must be made at an angle, so as to not allow the Peyote root to rot. When poor harvesting techniques are used, however, the root is damaged and the entire plant dies. This is the current situation in South Texas where Peyote grows naturally; but has been over-harvested to the point of listing as endangered species.The buttons are generally chewed, or boiled in water to produce a healing tea. The resulting infusion is extremely bitter to some people and, in most cases, the partaker experiences a high degree of nausea before the onset of the hallucinogenic effects. # Distribution and habitat L. williamsii is native in southern North America where it is only found in the extreme southwest of the US in the state of Texas, as well as much of northern Mexico. It is primarily found at elevations of 100 to 1500 m and exceptionally up to 1900 metres in the Chihuahuan desert, but is also present in the more mild climate of the state of Tamaulipas. Altogether, peyote can be found in the Mexican states of Chihuahua, Coahuila, Nuevo León, and Tamaulipas in the north to Durango, San Luis Potosi and Zacatecas in the south. Its habitat is primarily in desert scrub, particularly thorn scrub in Tamaulipas, and it is most common on or near limestone hills. # Uses The effective dose for mescaline is about 300 to 500 mg (equivalent to roughly 5 grams of dried peyote) and the effects last about 10 to 12 hours. When combined with appropriate set and setting, peyote is reported to trigger states of deep introspection and insight that have been described as being of a metaphysical or spiritual nature. At times, these can be accompanied by rich visual or auditory effects (see synesthesia). The flesh may also be applied topically as a galactogogue. # History From earliest recorded time, peyote has been used by indigenous peoples, such as the Huichol of northern Mexico and the Navajo in the southwestern United States, as a part of traditional religious rites. There is documented evidence of the religious, ceremonial, and healing uses of Peyote dating back to over 20,000 years. The tradition began to spread northward as part of a revival of native spirituality under the auspices of what came to be known as the Native American Church, whose members refer to Peyote as "the sacred medicine", and use it to combat spiritual, alcoholism and other physical and social ills. Between the 1880s and 1930s, U.S. authorities attempted to ban Native American religious rituals involving the Peyote, including the Ghost Dance. Native American Church is one among several religious organizations that use peyote as part of their religious practice. A resurgence of interest in the use of peyote was spawned in the 1970s by very detailed accounts of its use, properties and effects in the early works of writer Carlos Castaneda. Don Juan Matus, the name of Castaneda's teacher in the use of peyote, used the name "Mescalito" to refer to an entity that purportedly can be sensed by those using peyote to gain insight in how to live one's life well, but only if Mescalito accepted the user. Later works of Castaneda asserted that the use of such psychotropic substances was not necessary to achieve heightened awareness although his teacher advised its use was beneficial in helping to free the mind of some persons. An image of the plant, and by extension its possible usage, can be seen in the gonzo fist symbol attributed to Hunter S. Thompson. # Legality ## United States United States federal law (and many state laws) protect the harvest, possession, consumption and cultivation) of peyote as part of "bonafide religious ceremonies" (the federal regulation is 42 USC §1996a, "Traditional Indian religious use of the peyote sacrament," exempting only Native American use, while most state laws exempt any general "bonafide religious activity"). American jurisdictions enacted these specific statutory exemptions in reaction to the U.S. Supreme Court's decision in Employment Division v. Smith, Template:Ussc, which held that laws prohibiting the use of peyote that do not specifically exempt religious use nevertheless do not violate the Free Exercise Clause of the First Amendment. Although many American jurisdictions specifically allow religious use of peyote, religious or therapeutic use not under the aegis of the Native American Church has often been targeted by local law enforcement agencies, and non-natives attempting to establish spiritual centers based on the consumption of peyote as a sacrament or as medicine, such as the Peyote Foundation in Arizona, have been prosecuted. The Peyote Way Church of God in Arizona, is a spiritual center that welcomes all races to Peyotism. ## Canada Mescaline is listed as a Schedule III controlled substance under the Canadian Controlled Drugs and Substances Act, but peyote is specifically exempt. Peyote contains mescaline. ## International Article 32 of the Convention on Psychotropic Substances allows nations to exempt certain traditional uses of peyote from prohibition:	Peyote Template:ConvertIPA Lophophora williamsii, (lō-fof′ŏ-ră wil-yăm′sē-ī), better known by its common name Peyote, but also sometimes called Mescal Button or the Divine Cactus, is a small, spineless cactus whose native region extends from the southwestern United States, specifically in the southwestern part of Texas, through central Mexico. They are found primarily in the Chihuahuan desert and in the states of Tamaulipas and San Luis Potosi amongst scrub, especially when limestone is present in the soil. The cactus is well known for its psychoactive alkaloids and among these mescaline in particular. It is currently used world wide mainly as a recreational drug, an entheogen, and a tool in use to supplement various types of practices for transcendence including in meditation, psychonautics, and illegal psychedelic psychotherapy whether self administered or not. Certain American Indians tribes have used the plant for thousands of years prior to European arrival in the Americas, for both medicinal and religious purposes. The plant's pink flowers emerge from March through May, and in exceptional cases as late as September. # Description The cactus flowers sporadically, producing small pink fruit, which can be very delectable and bitter-sweet-tasting when eaten. The seeds are small and black, requiring hot and humid conditions to germinate. Peyote contains a large spectrum of phenethylamine alkaloids, the principal of which is mescaline. The mescaline content of Lophophora williamsii is about 0.4% fresh[2] (undried) and 3-6% dried.[2] All Lophophora species are extremely slow growing, often taking three years to reach flowering age in the wild (about the size of a golf ball, not including its root). Human cultivated specimens grow considerably faster, usually taking less than three years to go from seedling to mature flowering adult, and more rapid growth can be achieved by grafting Peyote onto mature San Pedro root stock; to expedite the age at which the Peyote flowers. Peyote contains two antibiotics named peyocactin. [3] The top of the cactus that grows above ground, also referred to as the crown, consists of disc-shaped buttons that are cut above the roots and sometimes dried. When done properly, the top of the root will callous over, and new buttons will eventually grow from the root left in the ground.[citation needed] The cut must be made at an angle, so as to not allow the Peyote root to rot.[citation needed] When poor harvesting techniques are used, however, the root is damaged and the entire plant dies. This is the current situation in South Texas where Peyote grows naturally; but has been over-harvested to the point of listing as endangered species.[citation needed]The buttons are generally chewed, or boiled in water to produce a healing tea. The resulting infusion is extremely bitter to some people and, in most cases, the partaker experiences a high degree of nausea before the onset of the hallucinogenic effects. # Distribution and habitat L. williamsii is native in southern North America where it is only found in the extreme southwest of the US in the state of Texas, as well as much of northern Mexico. It is primarily found at elevations of 100 to 1500 m and exceptionally up to 1900 metres in the Chihuahuan desert, but is also present in the more mild climate of the state of Tamaulipas. Altogether, peyote can be found in the Mexican states of Chihuahua, Coahuila, Nuevo León, and Tamaulipas in the north to Durango,[4] San Luis Potosi and Zacatecas in the south. Its habitat is primarily in desert scrub, particularly thorn scrub in Tamaulipas, and it is most common on or near limestone hills.[5] # Uses The effective dose for mescaline is about 300 to 500 mg (equivalent to roughly 5 grams of dried peyote) and the effects last about 10 to 12 hours. When combined with appropriate set and setting, peyote is reported to trigger states of deep introspection and insight that have been described as being of a metaphysical or spiritual nature. At times, these can be accompanied by rich visual or auditory effects (see synesthesia). The flesh may also be applied topically as a galactogogue. # History From earliest recorded time, peyote has been used by indigenous peoples, such as the Huichol of northern Mexico and the Navajo in the southwestern United States, as a part of traditional religious rites.[citation needed] There is documented evidence of the religious, ceremonial, and healing uses of Peyote dating back to over 20,000 years. The tradition began to spread northward as part of a revival of native spirituality under the auspices of what came to be known as the Native American Church, whose members refer to Peyote as "the sacred medicine", and use it to combat spiritual, alcoholism and other physical and social ills. Between the 1880s and 1930s, U.S. authorities attempted to ban Native American religious rituals involving the Peyote, including the Ghost Dance. Native American Church is one among several religious organizations that use peyote as part of their religious practice. A resurgence of interest in the use of peyote was spawned in the 1970s by very detailed accounts of its use, properties and effects in the early works of writer Carlos Castaneda. Don Juan Matus, the name of Castaneda's teacher in the use of peyote, used the name "Mescalito" to refer to an entity that purportedly can be sensed by those using peyote to gain insight in how to live one's life well, but only if Mescalito accepted the user. Later works of Castaneda asserted that the use of such psychotropic substances was not necessary to achieve heightened awareness although his teacher advised its use was beneficial in helping to free the mind of some persons. An image of the plant, and by extension its possible usage, can be seen in the gonzo fist symbol attributed to Hunter S. Thompson. # Legality ## United States United States federal law (and many state laws) protect the harvest, possession, consumption and cultivation) of peyote as part of "bonafide religious ceremonies" (the federal regulation is 42 USC §1996a, "Traditional Indian religious use of the peyote sacrament," exempting only Native American use, while most state laws exempt any general "bonafide religious activity"). American jurisdictions enacted these specific statutory exemptions in reaction to the U.S. Supreme Court's decision in Employment Division v. Smith, Template:Ussc, which held that laws prohibiting the use of peyote that do not specifically exempt religious use nevertheless do not violate the Free Exercise Clause of the First Amendment. Although many American jurisdictions specifically allow religious use of peyote, religious or therapeutic use not under the aegis of the Native American Church has often been targeted by local law enforcement agencies, and non-natives attempting to establish spiritual centers based on the consumption of peyote as a sacrament or as medicine, such as the Peyote Foundation in Arizona, have been prosecuted. The Peyote Way Church of God in Arizona, is a spiritual center that welcomes all races to Peyotism. ## Canada Mescaline is listed as a Schedule III controlled substance under the Canadian Controlled Drugs and Substances Act, but peyote is specifically exempt. Peyote contains mescaline. [1] ## International Article 32 of the Convention on Psychotropic Substances allows nations to exempt certain traditional uses of peyote from prohibition:	https://www.wikidoc.org/index.php/Peyote
24c22de643c4124c1ace62c1b1639a40752aa77d	wikidoc	Phlegm	Phlegm Please Take Over This Page and Apply to be Editor-In-Chief for this topic: There can be one or more than one Editor-In-Chief. You may also apply to be an Associate Editor-In-Chief of one of the subtopics below. Please mail us to indicate your interest in serving either as an Editor-In-Chief of the entire topic or as an Associate Editor-In-Chief for a subtopic. Please be sure to attach your CV and or biographical sketch. # Overview Phlegm (pronounced Template:IPA) is sticky fluid secreted by the typhoid membranes of animals. Its definition is limited to the mucus produced by the respiratory system, excluding that from the nasal passages, and particularly that which is expelled by coughing (sputum). Its composition varies, depending on climate, genetics and state of the immune system, but basically is a water-based gel consisting in glycoproteins, immunoglobulins, lipids, etc. In Hippocratic medicine, and for hundreds of years until about the 19th century, phlegm was counted as one of the four bodily humours, possessing the properties of coldness and wetness, and was responsible for apathetic and sluggish behaviour. This old belief is preserved in the word phlegmatic. # Colors of phlegm Phlegm may be of several different colors. - "Healthy" phlegm is normally clear or white. - Yellow phlegm is normally a sign of an infection. The initial state of the common flu when the phlegm is still clear is the most infectious period. When the phlegm turns into yellow, the body is already taking care of the infection. - Greenish or brownish phlegm is nearly always a sign of infection. Greenish or rusty phlegm or phlegm with rusty spots can also be a sign of pneumonia and/or internal micro-bleedings. - Coughing up brown phlegm is also a common symptom of smoking. This is due to resin sticking to the viscous texture of the phlegm and being ejected by the body. - Another type of phlegm often associated with smoking is brownish gray in color. This variant is encased in clear saliva. When spread out, the brown-gray "core" is shown to be grainy in composition, as opposed to holding together. This is simply dust and other foreign matter and may be caused by damage to the cilia, as in COPD patients. # Illnesses related to phlegm Phlegm may be a carrier of larvae of intestinal parasites (see hookworm). Bloody sputum can be a symptom of serious disease (such as tuberculosis and lung cancer), but can also be a relatively benign symptom of a minor disease (such as bronchitis). In the latter case, the sputum is normally lightly streaked with blood. Coughing up any significant quantity of blood is always a serious medical condition, and any person who experiences this should seek medical attention. Another case would be if you had a nose bleed and some blood went down your throat. Some blood could stick the some phlegm and cause bloody phlegm. # Phlegm and humourism Humourism holds that the human body is filled with four basic substances, called the four humours, which are held in balance when a person is healthy. All diseases and disabilities result from an excess or deficit in one of these humours. The four humours, corresponding to the four elements of earth, fire, water, and air, are black bile, yellow bile, phlegm, and blood, respectively.	Phlegm Please Take Over This Page and Apply to be Editor-In-Chief for this topic: There can be one or more than one Editor-In-Chief. You may also apply to be an Associate Editor-In-Chief of one of the subtopics below. Please mail us [1] to indicate your interest in serving either as an Editor-In-Chief of the entire topic or as an Associate Editor-In-Chief for a subtopic. Please be sure to attach your CV and or biographical sketch. # Overview Phlegm (pronounced Template:IPA) is sticky fluid secreted by the typhoid membranes of animals. Its definition is limited to the mucus produced by the respiratory system, excluding that from the nasal passages, and particularly that which is expelled by coughing (sputum). Its composition varies, depending on climate, genetics and state of the immune system, but basically is a water-based gel consisting in glycoproteins, immunoglobulins, lipids, etc. In Hippocratic medicine, and for hundreds of years until about the 19th century, phlegm was counted as one of the four bodily humours, possessing the properties of coldness and wetness, and was responsible for apathetic and sluggish behaviour. This old belief is preserved in the word phlegmatic. # Colors of phlegm Phlegm may be of several different colors. - "Healthy" phlegm is normally clear or white. - Yellow phlegm is normally a sign of an infection. The initial state of the common flu when the phlegm is still clear is the most infectious period. When the phlegm turns into yellow, the body is already taking care of the infection. - Greenish or brownish phlegm is nearly always a sign of infection. Greenish or rusty phlegm or phlegm with rusty spots can also be a sign of pneumonia and/or internal micro-bleedings. - Coughing up brown phlegm is also a common symptom of smoking. This is due to resin sticking to the viscous texture of the phlegm and being ejected by the body. - Another type of phlegm often associated with smoking is brownish gray in color. This variant is encased in clear saliva. When spread out, the brown-gray "core" is shown to be grainy in composition, as opposed to holding together. This is simply dust and other foreign matter and may be caused by damage to the cilia, as in COPD patients. # Illnesses related to phlegm Phlegm may be a carrier of larvae of intestinal parasites (see hookworm). Bloody sputum can be a symptom of serious disease (such as tuberculosis and lung cancer), but can also be a relatively benign symptom of a minor disease (such as bronchitis). In the latter case, the sputum is normally lightly streaked with blood. Coughing up any significant quantity of blood is always a serious medical condition, and any person who experiences this should seek medical attention. Another case would be if you had a nose bleed and some blood went down your throat. Some blood could stick the some phlegm and cause bloody phlegm. # Phlegm and humourism Humourism holds that the human body is filled with four basic substances, called the four humours, which are held in balance when a person is healthy. All diseases and disabilities result from an excess or deficit in one of these humours. The four humours, corresponding to the four elements of earth, fire, water, and air, are black bile, yellow bile, phlegm, and blood, respectively.	https://www.wikidoc.org/index.php/Phlegm
bd438362ff1203e03effdc4c4c6eece947c42460	wikidoc	Piedra	Piedra Piedra is a hair disease caused by a fungus. Types include: - White piedra - Black piedra # Gallery - Under a relatively-low magnification of 100X, this photomicrograph reveals some of the pathologic morphology displayed by a primate hair shaft indicative of the disease known as, “black piedra”, also known as “trichosporosis”, which is caused by the fungal organism, Piedraia hortae. From Public Health Image Library (PHIL). - This is a photomicrograph of a hair shaft with a condition called “black piedra” due to Piedraia hortae. From Public Health Image Library (PHIL). - This is a photomicrograph of the mycelium of the fungus Piedraia hortae, magnified 475X. From Public Health Image Library (PHIL). - This is a plate culture of Piedraia hortae, strain A272. From Public Health Image Library (PHIL).	Piedra Piedra is a hair disease caused by a fungus.[1] Types include: - White piedra - Black piedra # Gallery - Under a relatively-low magnification of 100X, this photomicrograph reveals some of the pathologic morphology displayed by a primate hair shaft indicative of the disease known as, “black piedra”, also known as “trichosporosis”, which is caused by the fungal organism, Piedraia hortae. From Public Health Image Library (PHIL). [2] - This is a photomicrograph of a hair shaft with a condition called “black piedra” due to Piedraia hortae. From Public Health Image Library (PHIL). [2] - This is a photomicrograph of the mycelium of the fungus Piedraia hortae, magnified 475X. From Public Health Image Library (PHIL). [2] - This is a plate culture of Piedraia hortae, strain A272. From Public Health Image Library (PHIL). [2]	https://www.wikidoc.org/index.php/Piedra
b1f0f709b0c43b7b2f2e09d66e8d4fd40eb99feb	wikidoc	Pilosa	Pilosa Please Take Over This Page and Apply to be Editor-In-Chief for this topic: There can be one or more than one Editor-In-Chief. You may also apply to be an Associate Editor-In-Chief of one of the subtopics below. Please mail us to indicate your interest in serving either as an Editor-In-Chief of the entire topic or as an Associate Editor-In-Chief for a subtopic. Please be sure to attach your CV and or biographical sketch. The order Pilosa is a group of placental mammals, extant today only in the Americas. It includes the anteaters and sloths. The origins of the order can be traced back as far as the early Tertiary (about 60 million years ago, or only a short time after the end of the dinosaur era). The presence of these animals in North America is explained by the Great American Interchange. Until recently, Pilosa was lumped with the armadillos in the order Xenarthra. Xenarthra is now generally regarded as a superorder. In the past, these families were classified together with the pangolins and Aardvark as the order Edentata (meaning toothless, because the members do not have front incisor teeth or molars, or have poorly-developed molars). It was subsequently realized that Edentata was polyphyletic—that it contained unrelated families and was thus invalid. # Classification Order Pilosa - Suborder Vermilingua Family Cyclopedidae Silky Anteater, Cyclopes didactylus Family Myrmecophagidae Giant Anteater, Myrmecophaga tridactyla Northern Tamandua, Tamandua mexicana Southern Tamandua, Tamandua tetradactyla - Family Cyclopedidae Silky Anteater, Cyclopes didactylus - Silky Anteater, Cyclopes didactylus - Family Myrmecophagidae Giant Anteater, Myrmecophaga tridactyla Northern Tamandua, Tamandua mexicana Southern Tamandua, Tamandua tetradactyla - Giant Anteater, Myrmecophaga tridactyla - Northern Tamandua, Tamandua mexicana - Southern Tamandua, Tamandua tetradactyla - Suborder Folivora Family Bradypodidae: three-toed sloths Pygmy Three-toed Sloth, Bradypus pygmaeus Brown-throated Three-toed Sloth, Bradypus variegatus Pale-throated Three-toed Sloth, Bradypus tridactylus Maned Three-toed Sloth, Bradypus torquatus Family Megalonychidae: two-toed sloths Hoffman's Two-toed Sloth, Choloepus hoffmanni Southern Two-toed Sloth, Choloepus didactylus - Family Bradypodidae: three-toed sloths Pygmy Three-toed Sloth, Bradypus pygmaeus Brown-throated Three-toed Sloth, Bradypus variegatus Pale-throated Three-toed Sloth, Bradypus tridactylus Maned Three-toed Sloth, Bradypus torquatus - Pygmy Three-toed Sloth, Bradypus pygmaeus - Brown-throated Three-toed Sloth, Bradypus variegatus - Pale-throated Three-toed Sloth, Bradypus tridactylus - Maned Three-toed Sloth, Bradypus torquatus - Family Megalonychidae: two-toed sloths Hoffman's Two-toed Sloth, Choloepus hoffmanni Southern Two-toed Sloth, Choloepus didactylus - Hoffman's Two-toed Sloth, Choloepus hoffmanni - Southern Two-toed Sloth, Choloepus didactylus	Pilosa Please Take Over This Page and Apply to be Editor-In-Chief for this topic: There can be one or more than one Editor-In-Chief. You may also apply to be an Associate Editor-In-Chief of one of the subtopics below. Please mail us [1] to indicate your interest in serving either as an Editor-In-Chief of the entire topic or as an Associate Editor-In-Chief for a subtopic. Please be sure to attach your CV and or biographical sketch. The order Pilosa is a group of placental mammals, extant today only in the Americas. It includes the anteaters and sloths. The origins of the order can be traced back as far as the early Tertiary (about 60 million years ago, or only a short time after the end of the dinosaur era). The presence of these animals in North America is explained by the Great American Interchange. Until recently, Pilosa was lumped with the armadillos in the order Xenarthra. Xenarthra is now generally regarded as a superorder. In the past, these families were classified together with the pangolins and Aardvark as the order Edentata (meaning toothless, because the members do not have front incisor teeth or molars, or have poorly-developed molars). It was subsequently realized that Edentata was polyphyletic—that it contained unrelated families and was thus invalid. # Classification Order Pilosa - Suborder Vermilingua Family Cyclopedidae Silky Anteater, Cyclopes didactylus Family Myrmecophagidae Giant Anteater, Myrmecophaga tridactyla Northern Tamandua, Tamandua mexicana Southern Tamandua, Tamandua tetradactyla - Family Cyclopedidae Silky Anteater, Cyclopes didactylus - Silky Anteater, Cyclopes didactylus - Family Myrmecophagidae Giant Anteater, Myrmecophaga tridactyla Northern Tamandua, Tamandua mexicana Southern Tamandua, Tamandua tetradactyla - Giant Anteater, Myrmecophaga tridactyla - Northern Tamandua, Tamandua mexicana - Southern Tamandua, Tamandua tetradactyla - Suborder Folivora Family Bradypodidae: three-toed sloths Pygmy Three-toed Sloth, Bradypus pygmaeus Brown-throated Three-toed Sloth, Bradypus variegatus Pale-throated Three-toed Sloth, Bradypus tridactylus Maned Three-toed Sloth, Bradypus torquatus Family Megalonychidae: two-toed sloths Hoffman's Two-toed Sloth, Choloepus hoffmanni Southern Two-toed Sloth, Choloepus didactylus - Family Bradypodidae: three-toed sloths Pygmy Three-toed Sloth, Bradypus pygmaeus Brown-throated Three-toed Sloth, Bradypus variegatus Pale-throated Three-toed Sloth, Bradypus tridactylus Maned Three-toed Sloth, Bradypus torquatus - Pygmy Three-toed Sloth, Bradypus pygmaeus - Brown-throated Three-toed Sloth, Bradypus variegatus - Pale-throated Three-toed Sloth, Bradypus tridactylus - Maned Three-toed Sloth, Bradypus torquatus - Family Megalonychidae: two-toed sloths Hoffman's Two-toed Sloth, Choloepus hoffmanni Southern Two-toed Sloth, Choloepus didactylus - Hoffman's Two-toed Sloth, Choloepus hoffmanni - Southern Two-toed Sloth, Choloepus didactylus	https://www.wikidoc.org/index.php/Pilosa
ba0fe4eff3c19dbc5ff9c10ce72fd508fb93201d	wikidoc	Piping	Piping Within industry, piping is a system of pipes used to convey fluids and gases, from one location to another. The engineering discipline of piping design studies the best and most efficient manner of transporting fluid to where it is needed. Industrial process piping (and accompanying in-line components) can be manufactured from wood, glass, steel, aluminum, plastic, copper, and concrete. The in-line components, known as fittings, valves, and other devices, typically sense and control the pressure, flow rate and temperature of the transmitted fluid, and usually are included when one discusses the concept of piping design. Piping systems are documented in Piping and Instrumentation Diagrams. If necessary, pipes can be cleaned by the tube cleaning process. Plumbing is a piping system that most people are familiar with, as it constitutes the form of fluid transportation that is used to provide potable water and fuels to their homes and business. Plumbing pipes also remove waste in the form of sewage, and allow venting of sewage gases to the outdoors. Fire sprinkler systems also use piping, and may transport potable or nonpotable water, or other fire-suppression fluids. Piping also has many other industrial applications, which are crucial for moving raw and semi-processed fluids for refining into more useful products. Some of the more exotic materials of construction are titanium, chrome-moly and various other steel alloys. # Pipe stress analysis Process piping and power piping are typically checked by pipe stress engineers to verify that the routing, nozzle loads, hangers, and supports are properly placed and selected such that allowable pipe stress is not exceeded under the appropriate ASME code. This checking is usually done with the assistance of a finite element pipe stress analysis program such as Caesar II, ROHR2, CAEPIPE and AUTOPIPE.	Piping Within industry, piping is a system of pipes used to convey fluids and gases, from one location to another. The engineering discipline of piping design studies the best and most efficient manner of transporting fluid to where it is needed.[1][2] Industrial process piping (and accompanying in-line components) can be manufactured from wood, glass, steel, aluminum, plastic, copper, and concrete. The in-line components, known as fittings, valves, and other devices, typically sense and control the pressure, flow rate and temperature of the transmitted fluid, and usually are included when one discusses the concept of piping design. Piping systems are documented in Piping and Instrumentation Diagrams. If necessary, pipes can be cleaned by the tube cleaning process. Plumbing is a piping system that most people are familiar with, as it constitutes the form of fluid transportation that is used to provide potable water and fuels to their homes and business. Plumbing pipes also remove waste in the form of sewage, and allow venting of sewage gases to the outdoors. Fire sprinkler systems also use piping, and may transport potable or nonpotable water, or other fire-suppression fluids. Piping also has many other industrial applications, which are crucial for moving raw and semi-processed fluids for refining into more useful products. Some of the more exotic materials of construction are titanium, chrome-moly and various other steel alloys. # Pipe stress analysis Process piping and power piping are typically checked by pipe stress engineers to verify that the routing, nozzle loads, hangers, and supports are properly placed and selected such that allowable pipe stress is not exceeded under the appropriate ASME code.[3][4] This checking is usually done with the assistance of a finite element pipe stress analysis program such as Caesar II, ROHR2, CAEPIPE and AUTOPIPE.	https://www.wikidoc.org/index.php/Piping
f7d5ecb59cfe1546fb42647ffea71b4f930b81aa	wikidoc	Plexus	Plexus Please Take Over This Page and Apply to be Editor-In-Chief for this topic: There can be one or more than one Editor-In-Chief. You may also apply to be an Associate Editor-In-Chief of one of the subtopics below. Please mail us to indicate your interest in serving either as an Editor-In-Chief of the entire topic or as an Associate Editor-In-Chief for a subtopic. Please be sure to attach your CV and or biographical sketch. # Overview A plexus is a network. It has more specific meanings in multiple fields. # Biology In biology, plexus has multiple meanings. ## Nervous system In many animals the processes of neurons join together to form a plexus or nerve net. This is the characteristic form of nervous system in the coelenterates and persists with modifications in the flatworms. The nerves of the radially symmetric echinoderms also take this form, where a plexus underlies the ectoderm of these animals and, deeper in the body, other nerve cells form plexuses of limited extent. In vertebrates nerves branch and rejoin in some parts of the body, for example the brachial plexus made up of the spinal nerves which enter the arm and the solar plexus above the stomach. Almost a hundred such plexuses have been named in the human body, but the four primary nerve plexuses are the cervical plexus, brachial plexus, lumbar plexus, and the sacral plexus. ## Circulatory system A plexus is also a network of blood vessels, with the choroid plexuses of the brain being the most commonly mentioned example. Choroid plexuses are very thin and vascular roof plates of the most anterior and most posterior cavities of the brain which expand into the interiors of the cavities. Other vascular plexuses are found elsewhere in the body. de:Plexus (Medizin)	Plexus Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Please Take Over This Page and Apply to be Editor-In-Chief for this topic: There can be one or more than one Editor-In-Chief. You may also apply to be an Associate Editor-In-Chief of one of the subtopics below. Please mail us [2] to indicate your interest in serving either as an Editor-In-Chief of the entire topic or as an Associate Editor-In-Chief for a subtopic. Please be sure to attach your CV and or biographical sketch. # Overview A plexus is a network. It has more specific meanings in multiple fields. # Biology In biology, plexus has multiple meanings. ## Nervous system In many animals the processes of neurons join together to form a plexus or nerve net. This is the characteristic form of nervous system in the coelenterates and persists with modifications in the flatworms. The nerves of the radially symmetric echinoderms also take this form, where a plexus underlies the ectoderm of these animals and, deeper in the body, other nerve cells form plexuses of limited extent. In vertebrates nerves branch and rejoin in some parts of the body, for example the brachial plexus made up of the spinal nerves which enter the arm and the solar plexus above the stomach. Almost a hundred such plexuses have been named in the human body, but the four primary nerve plexuses are the cervical plexus, brachial plexus, lumbar plexus, and the sacral plexus. ## Circulatory system A plexus is also a network of blood vessels, with the choroid plexuses of the brain being the most commonly mentioned example. Choroid plexuses are very thin and vascular roof plates of the most anterior and most posterior cavities of the brain which expand into the interiors of the cavities. Other vascular plexuses are found elsewhere in the body. Template:SIB de:Plexus (Medizin) Template:WikiDoc Sources	https://www.wikidoc.org/index.php/Plexus
c75022b8bc6012a3e15aa0e7bf2ed5e21228b0d9	wikidoc	Potash	Potash Potash (or carbonate of potash) is an impure form of potassium carbonate (K2CO3). Potash has been used since antiquity in the manufacture of glass and soap and as a fertilizer. The name comes from the English words pot and ash, referring to its discovery in the water-soluble fraction of wood ash. The term has become somewhat ambiguous due to the substitution in fertilizers of cheaper potassium salts, such as potassium chloride (KCl) or potassium oxide (K2O), to which the same common name is now sometimes also applied. In addition, potassium hydroxide (KOH) is commonly called caustic potash, an additional source of confusion. The element potassium derives its English name from potash. A number of chemical compounds containing potassium use the word potash in their traditional names: # Potash production and trade ## History Since the 14th century, potash was widely produced by Ethiopia. It was their number one export up until the 20th century; however after the Ethiopian War against Kenya it became irrelevant. Potash was one of the most important industrial chemicals in Canada. It was refined from the ashes of broadleaved trees and produced primarily in the forested areas of Europe, Russia, and North America. The first U.S. patent was issued in 1790 to Samuel Hopkins for an improvement "in the making Pot ash and Pearl ash by a new Apparatus and Process." Potash production provided late-18th and early-19th century settlers in North America a way to obtain badly needed cash and credit as they cleared their wooded land for crops. To make full use of their land, excess wood, including stumps, needed to be disposed. The easiest way to accomplish this was to burn any wood not needed for fuel or construction. Ashes from hardwood trees could then be used to make lye, which could either be used to make soap or boiled down to produce valuable potash. Hardwood could generate ashes at the rate of 60 to 100 bushels per acre (500 to 900 m³/km²). In 1790, ashes could be sold for $3.25 to $6.25 per acre ($800 to $1500/km²) in rural New York State – nearly the same rate as hiring a laborer to clear the same area. ## Potash as baking aid Potash along with hartshorn is also used as a baking aid similar to baking soda in old German Christmas bakery receipes such as Lebkuchen (ginger bread). ## Potash in the modern era In 2005, Canada was the largest producer of potash with almost one-fourth of the world share followed by Russia and Belarus in Soligorsk, reports the British Geological Survey. Natural potash deposits can also be mined; a substantial deposit is also located in New Brunswick. The most significant reserve in New Brunswick occurs in formations held by the Windsor group, a Canadian investment bank, where a potash resource base of more than 1.6 billion t KCl has been estimated. Many other areas also have the resources for potash production. It should be noted that unlike other producers, Israel's Dead Sea Works and Jordan's Arab Potash Company use solar evaporation pans in the Dead Sea to produce carnallite from which potassium chloride is produced.	Potash Potash (or carbonate of potash) is an impure form of potassium carbonate (K2CO3). Potash has been used since antiquity in the manufacture of glass and soap and as a fertilizer. The name comes from the English words pot and ash, referring to its discovery in the water-soluble fraction of wood ash. The term has become somewhat ambiguous due to the substitution in fertilizers of cheaper potassium salts, such as potassium chloride (KCl) or potassium oxide (K2O)[1], to which the same common name is now sometimes also applied. In addition, potassium hydroxide (KOH) is commonly called caustic potash, an additional source of confusion. The element potassium derives its English name from potash. A number of chemical compounds containing potassium use the word potash in their traditional names: # Potash production and trade ## History Since the 14th century, potash was widely produced by Ethiopia. It was their number one export up until the 20th century; however after the Ethiopian War against Kenya it became irrelevant. Potash was one of the most important industrial chemicals in Canada. It was refined from the ashes of broadleaved trees and produced primarily in the forested areas of Europe, Russia, and North America. The first U.S. patent was issued in 1790 to Samuel Hopkins for an improvement "in the making Pot ash and Pearl ash by a new Apparatus and Process."[2] Potash production provided late-18th and early-19th century settlers in North America a way to obtain badly needed cash and credit as they cleared their wooded land for crops. To make full use of their land, excess wood, including stumps, needed to be disposed. The easiest way to accomplish this was to burn any wood not needed for fuel or construction. Ashes from hardwood trees could then be used to make lye, which could either be used to make soap or boiled down to produce valuable potash. Hardwood could generate ashes at the rate of 60 to 100 bushels per acre (500 to 900 m³/km²). In 1790, ashes could be sold for $3.25 to $6.25 per acre ($800 to $1500/km²) in rural New York State – nearly the same rate as hiring a laborer to clear the same area. ## Potash as baking aid Potash along with hartshorn is also used as a baking aid similar to baking soda in old German Christmas bakery receipes such as Lebkuchen (ginger bread). ## Potash in the modern era In 2005, Canada was the largest producer of potash with almost one-fourth of the world share followed by Russia and Belarus in Soligorsk, reports the British Geological Survey. Natural potash deposits can also be mined; a substantial deposit is also located in New Brunswick. The most significant reserve in New Brunswick occurs in formations held by the Windsor group, a Canadian investment bank, where a potash resource base of more than 1.6 billion t KCl has been estimated.[3] Many other areas also have the resources for potash production. It should be noted that unlike other producers, Israel's Dead Sea Works and Jordan's Arab Potash Company use solar evaporation pans in the Dead Sea to produce carnallite from which potassium chloride is produced. # External links - The Potash Trade in North America - Potash Production in Northern Sweden: History and Ecological Effects of a Pre-industrial Forest Exploitation - They Burned The Woods and Sold the Ashes - Henry M. Paynter, The First Patent, Invention & Technology, Fall 1990 - World Agriculture and Fertilizer Markets Map - The First U.S. Patent, issued for a method of potash production - "Digging for Potash, Mining Companies Encounter An Iron Will" magazine article - Russia reaps rich harvest with potash # References and notes - ↑ In actuality, fertilizer never contains potassium oxide, per se, because it is both a caustic and a highly reactive chemical. It is so reactive that is must be stored under kerosene, like metallic potassium. However, it was decided to standardize the reporting of potassium in terms of the oxide. The potassium oxide itself is even barely available in the commercial world, difficult to obtain even as a reagent, though. - ↑ Kids - Time Machine - Historic Press Releases - USPTO - ↑ Potash da:Potaske de:Kaliumcarbonat he:אשלג nl:Potas no:Pottaske sr:Поташ fi:Potaska sv:Pottaska is:Pottaska	https://www.wikidoc.org/index.php/Potash
2530001bec13a43f8dc98fbbcdf8838357e6188d	wikidoc	Potato	Potato The potato is the term which applies either to the starchy tuberous crop from the perennial plant Solanum tuberosum of the Solanaceae, or nightshade, family, or to the plant itself. They are the world's most widely grown tuber crop, and the fourth largest food crop in terms of fresh produce — after rice, wheat, and maize ('corn'). Potatoes originated in the area of modern day Peru and then spread from South America to Spain and from there to the rest of the world after European colonization in the late 1400s and early 1500s. In the Southern Bolivian town of San Andreas, as many as 300 varieties may be showcased at the town's annual potato festival. They soon became an important food staple and field crop. For instance, the potato was a staple food for sailors in Spanish ships. After the wreck of the Spanish Armada in 1588, Irish coastal villagers rescued potatoes and planted them. In 1845, a fungal disease, Phytophthora infestans, also known as late blight, spread rapidly through the poorer communities of western Ireland, resulting in the Great Irish Famine. Unfortunately the local population had come to rely heavily on the potato and when crops failed, year after year, huge numbers of people died. Others emigrated, largely to the United States, blaming the British government for the situation. The potato is also strongly associated with Idaho, Maine, North Dakota, Prince Edward Island, Ireland, Jersey and Russia because of its large role in the agricultural economy and history of these regions. # Etymology The English word potato comes from Spanish patata, ultimately from Nahuatl potatl, potentially its first name. Bulgarian картоф, as well as Russian картофель and German Kartoffel, derive from the Italian word tartufoli, which was given to potato because of its similarity to truffles (Italian: tartufo). Another common name is "ground apple": pomme de terre in French, aardappel in Dutch, תפוח אדמה in Hebrew (often written just as פוד), and Erdapfel in Austrian German. An analogous name is Finnish as peruna, which comes from the old Swedish term jordpäron "earth pear". In 16th century French, pomme meant "fruit", thus pomme de terre meant "ground fruit" and was probably literally loan translated to other languages when potatoes were introduced. In Polish potato is called just ziemniaki, and in Slovak zemiak, from the word for "ground". In several northern Indian languages and in Nepali the potato is called alu and in Indonesian kentang. Different names for the potato developed in China's various regions, the most widely used names in standard Chinese today are "horse-bell yam" (马铃薯 - mǎlíngshǔ), "earth bean" (土豆 - tǔdòu), and "foreign taro" (洋芋 - yángyù). # Description Potato plants grow high to the ground and bear yellow to silver flowers with yellow stamens. Potatoes are cross-pollinated mostly by bumblebees that carry pollen from other potato plants, but a substantial amount of self-fertilizing occurs as well. Any potato variety can also be propagated vegetatively by planting tubers, pieces of tubers, cut to include at least one or two eyes, or also by cuttings, a practice used in greenhouses for the production of healthy seed tubers. Some commercial potato varieties do not produce seeds at all (they bear imperfect flowers) and are propagated only from tuber pieces. Confusingly, these tubers or tuber pieces are called "seed potatoes". After potato plants flower, some varieties will produce small green fruits that resemble green cherry tomatoes. Each fruit can contain up to 300 true seeds. One can separate seeds from the fruits by putting them in a blender on a slow speed with some water, then leaving them in water for a day so that the seeds will sink and the rest of the fruit will float. All new potato varieties are grown from seeds, also called "true seed" or "botanical seed" to distinguish it from seed tubers. # Origin and history There is general agreement among contemporary botanists that the potato originated in the Andes, all the way from Colombia to northern Argentina, but with a concentration of genetic diversity, both in the form of cultivated and wild species, in the area of modern day Peru. The potatoes cultivated in the Andes are not all the same species. The major species is Solanum tuberosum ssp. andigena (a tetraploid with 48 chromosomes,) then there are four diploid species (with 24 chromosomes) by the names of Solanum stenotomum, Solanum phureja, Solanum goniocalyx and Solanum ajanhuiri. There are two triploid species (with 36 chromosomes) Solanum chaucha and Solanum juzepczukii, and finally, there is one pentaploid cultivated species (with 60 chromosomes) called Solanum curtilobum. Andean potatoes are adapted to short day conditions and Chilean potatoes to long day conditions. There is sufficient evidence that the tetraploid Andean short day potato was the one that first arrived in Southern Spain in about 1565, from where it spread to the rest of Europe, adapting to European long day conditions in a period of about two hundred years. In order to botanically distinguish potatoes adapted to short days from those thriving and producing tubers under long day conditions, Solanum tuberosum has been split into two subspecies by present-day taxonomists, Solanum tuberosum ssp. tuberosum (adapted to long days) and Solanum tuberosum ssp. andigena (adapted to short days.) Apart from their different photoperiodic reaction, these two subspecies are also distinct morphologically, though the differences are apparent only to an experienced taxonomist. Russian taxonomists did, in fact, create two different species in the early part of the 20th century, Solanum tuberosum and Solanum andigenum, to mark the same distinction. The process of adaptation to long days has happened once before as the potato moved from the Andes to the south of the continent. This was before the Europeans arrived in South America. Chile still has a large amount of valuable potato germplasm adapted to long days. Historical and genetic evidence suggests that the potato reached India not very much later than Europe, probably taken there by the Portuguese. In isolated areas in the Himalayas of India and Nepal, so called "desi" potatoes are still grown, and they are very similar to the short day adapted modern Andean potato, Solanum tuberosum ssp. andigena. There are about five thousand potato varieties world wide. Three thousand of them are found in the Andes alone, mainly in Peru, Bolivia, Ecuador and Colombia. They belong to eight or nine species, depending on the taxonomic school. Apart from the five thousand cultivated varieties, there are about 200 wild species, many of which can be cross-bred with cultivated species, which has been done repeatedly to transfer resistances to certain pests and diseases from the gene pool of wild species to the gene pool of cultivated potato species. The list of varieties found in European, North American or Asian markets is very limited, and these varieties are all of the same species, Solanum tuberosum ssp. tuberosum. These potatoes are often referred to as "Irish" potatoes in the English speaking world because of their association with the Great Irish Famine, which began in 1845 and lasted for six years. The Irish peasant population had become highly dependent on the potato because of the relatively large amount of food that could be produced on fairly small holdings. Immigrant farmers from the Palatinate region of Germany brought their own crops, such as turnips, to Western Ireland. They were much less dependent on the potato than their native Irish neighbors and were largely spared the effects of the potato famine. The disease killing the Irish potato crop was the late blight fungus Phytophthora infestans. The long lasting aftereffects of this famine are well known and well documented. What is less well known is the role of the British during the potato famine. Rich aristocratic British landowners continued to export grain from Ireland to other parts of the world even as tens of thousands of Irish were dying of starvation. However, there were some British owned estates where not one Irish peasant starved during the famine. Authors like Salaman have written in detail about that situation, which has also been recognized by contemporary British historians. Most modern potatoes grown in North America arrived through European settlement and not independently from the South American sources. Still, one wild potato species, Solanum fendleri, is found as far north as Texas and used in breeding for resistance to a nematode species attacking cultivated potatoes. A secondary center of genetic variability of the potato is Mexico, where important wild species are found that have been used extensively in modern breeding, such as the hexaploid Solanum demissum, as a source of resistance to the devastating late blight disease. The potato became an important staple crop in northern Europe as the climate changed due to the Little Ice Age, when traditional crops in this region did not produce as reliably as before. At times when and where most other crops would fail, potatoes could still typically be relied upon to contribute adequately to food supplies during the colder years. The potato was not popular in France during this time, and it is believed that some of the infamous famines could have been lessened if French farmers had adopted it. Today, the potato forms an important part of the traditional cuisine of the British Isles, northern Europe, central Europe and eastern Europe. As of 2007, Germany has a higher consumption of potato per capita than any other country. # Nutrition Nutritionally, potatoes are best known for their carbohydrate content (approximately 26 grams in a medium potato). Starch is the predominant form of carbohydrate found in potatoes. A small but significant portion of the starch in potatoes is resistant to enzymatic digestion in the stomach and small intestine and, thus, reaches the large intestine essentially intact. This resistant starch is considered to have similar physiological effects and health benefits of fiber (e.g., provide bulk, offer protection against colon cancer, improve glucose tolerance and insulin sensitivity, lower plasma cholesterol and triglyceride concentrations, increase satiety, and possibly even reduce fat storage) (Cummings et al. 1996; Hylla et al 1998; Raban et al. 1994). The amount of resistant starch found in potatoes is highly dependent upon preparation methods. Cooking and then cooling potatoes significantly increases resistant starch. For example, cooked potato starch contains about 7% resistant starch, which increases to about 13% upon cooling (Englyst et al. 1992). Potatoes contain a number of important vitamins and minerals. A medium potato (150g/5.3 oz) with the skin provides 27 mg vitamin C (45% of the Daily Value (DV)), 620 mg of potassium (18% of DV), 0.2 mg vitamin B6 (10% of DV) and trace amounts of thiamin, riboflavin, folate, niacin, magnesium, phosphorus, iron, and zinc. Moreover, the fiber content of a potato with skin (2 grams) equals that of many whole grain breads, pastas, and cereals. In addition to vitamins, minerals and fiber, potatoes also contain an assortment of phytochemicals, such as carotenoids and polyphenols. The notion that “all of the potato’s nutrients” are found in the skin is an urban legend. While the skin does contain approximately half of the total dietary fiber, the majority (more than 50%) of the nutrients are found within the potato itself. The cooking method used can significantly impact the nutrient availability of the potato. New and fingerling potatoes offer the advantage that they contain fewer toxic chemicals. Such potatoes offer an excellent source of nutrition. Peeled, long-stored potatoes have less nutritional value, although they still have potassium and vitamin B. Potatoes are often broadly classified as “high” on the glycemic index (GI) and thus are frequently excluded from the diets of individuals trying to follow a “low GI” eating regimen. In fact, the GI of potatoes can vary considerably depending on the type (i.e., red vs. russet vs. white vs. Prince Edward), origin (i.e., where it was grown), preparation methods (i.e., cooking method, whether it is eaten hot or cold, whether it is mashed or cubed or consumed whole, etc), and what it is consumed with (i.e., the addition of various high fat or high protein toppings) (Fernandes et al. 2006). Potatoes are prepared in many ways: skin-on or peeled, whole or cut up, with seasonings or without. The only requirement involves cooking to break down the starch. Most potato dishes are served hot, but some are first cooked then served cold, notably potato salad and potato chips/crisps. Common dishes are: mashed potatoes, which are first boiled (usually peeled), and then mashed with milk or yogurt and butter; whole baked potatoes; boiled or steamed potatoes; French-fried potatoes or chips; cut into cubes and roasted; scalloped, diced, or sliced and fried (home fries); grated into small thin strips and fried (hash browns); grated and formed into dumplings, Rösti or potato pancakes. Unlike many foods, potatoes can also be easily cooked in a microwave oven and still retain nearly all of their nutritional value, provided that they are covered in ventilated plastic wrap to prevent moisture from escaping—this method produces a meal very similar to a steamed potato while retaining the appearance of a conventionally baked potato. Potato chunks also commonly appear as a stew ingredient. Potatoes are boiled between 10 and 25 minutes, depending on size and type, to become soft. # Regional dishes ## Latin America Peruvian Cuisine naturally contains the potato as a primary ingredient in many dishes, as around 3,000 varieties of this tuber are grown there. Some of the more famous dishes include Papa a la huancaina, Papa rellena, Ocopa, Carapulcra, Causa and Cau Cau among many others. ## Europe Mashed potatoes form a major component of several traditional dishes from the British Isles such as shepherd's pie, bubble and squeak, champ and the 'mashit tatties' (Scots language) which accompany haggis. They are also often sautéed to accompany a meal. Colcannon is a traditional Irish dish involving mashed potato combined with shredded cabbage and onion. Boxty pancakes are eaten all over Ireland, although associated especially with the north, and in Irish diaspora communities: they are traditionally made with grated potatoes, soaked to loosen the starch and mixed with flour, buttermilk and baking powder. A variant eaten and sold in Lancashire, especially Liverpool, is made with cooked and mashed potatoes. In Northern Europe, especially Denmark, Sweden and Finland, newly harvested, early ripening varieties are considered a special delicacy. Boiled whole and served with dill, these "new potatoes" are traditionally consumed together with Baltic herring. In the UK, new potatoes are cooked with mint and served with a little melted butter - Jersey Royal potatoes are the most prized new potatoes, and have their own Protected Designation of Origin. Potatoes are very popular in continental Europe as well. In Italy, they serve to make a type of pasta called gnocchi. Similarly, cooked and mashed potatoes or potato flour can be used in the knödel or dumpling eaten with or added to meat dishes all over central and Eastern Europe, but especially in Bavaria and Luxembourg. Potatoes form one of the main ingredients in many soups such as the pseudo-French vichyssoise and Albanian potato and cabbage soup. In western Norway, komle is popular. A traditional Canary Islands dish is Canarian wrinkly potatoes or Papas arrugadas. Patatas bravas, a dish of fried potatoes in a spicy tomato sauce, is a near-universal constituent of Spanish tapas. ## North America In the United States, potatoes have become one of the most widely consumed crops, and thus have a variety of preparation methods and condiments. One popular favorite involves a baked potato with cheddar cheese (or sour cream and chives) on top, and in New England "smashed potatoes" (a chunkier variation on mashed potatoes, retaining the peel) have great popularity. Potato flakes are popular as an instant variety of mashed potatoes, which reconstitute into mashed potatoes by adding water, plus butter & salt for taste. A regional dish of Central New York, salt potatoes are bite-sized new potatoes boiled in water saturated with salt then served with melted butter. A traditional Acadian dish from New Brunswick is known as poutine râpée. The Acadian poutine is a ball of grated and mashed potato, salted, sometimes filled with pork in the center, and boiled. The result is a moist ball about the size of a baseball. It is commonly eaten with salt and pepper or brown sugar. It is believed to have originated from the German Klöße, prepared by early German settlers who lived among the Acadians. Poutine, by contrast, is a hearty serving of french fries, fresh cheese curds and hot gravy. Tracing its origins to Quebec in the 1950s, it has become popular across Canada and can usually be found where Canadians gather abroad. # Toxic compounds in potatoes Potatoes contain glycoalkaloids, toxic compounds, of which the most prevalent are solanine and chaconine. Cooking at high temperatures (over 170 °C or 340 °F) partly destroys these. The concentration of glycoalkaloid in wild potatoes suffices to produce toxic effects in humans. Glycoalkaloids occur in the greatest concentrations just underneath the skin of the tuber, and they increase with age and exposure to light. Glycoalkaloids may cause headaches, diarrhea, cramps and in severe cases coma and death; however, poisoning from potatoes occurs very rarely. Light exposure also causes greening, thus giving a visual clue as to areas of the tuber that may have become more toxic; however, this does not provide a definitive guide, as greening and glycoalkaloid accumulation can occur independently of each other. Some varieties of potato contain greater glycoalkaloid concentrations than others; breeders developing new varieties test for this, and sometimes have to discard an otherwise promising cultivar. Breeders try to keep solanine levels below 200 mg/kg (200 ppmw). However, when these commercial varieties turn green, even they can approach concentrations of solanine of 1000 mg/kg (1000 ppmw). In normal potatoes though, analysis has shown solanine levels may be as little as 3.5% of the breeders' maximum, with 7–187 mg/kg being found. The National Toxicology Program suggests that the average American consumes at most 12.5 mg/person/day of solanine from potatoes (note that the toxic dose is actually several times this, depending on body weight). Dr. Douglas L. Holt, the State Extension Specialist for Food Safety at the University of Missouri - Columbia, notes that no reported cases of potato-source solanine poisoning have occurred in the U.S. in the last 50 years and most cases involved eating green potatoes or drinking potato-leaf tea. Solanine is also found in other plants, mainly in the mostly-deadly nightshade family, which includes a minority of edible plants including the potato and the tomato, and other typically more dangerous plants like tobacco. This poison affects the nervous system causing weakness and confusion. - Solanine - List of poisonous plants - Sites with information about the safety of green potatoes: # Cultivation Potatoes are generally grown from the eyes of another potato and not from seed. Home gardeners often plant a piece of potato with two or three eyes in a hill of mounded soil. Commercial growers plant potatoes as a row crop using seed tubers, young plants or microtubers and may mound the entire row. At harvest time, gardeners generally dig up potatoes with a long-handled, three-prong "grape" (or graip), i.e. a spading fork, or a potato hook which is similar to the graip, except the tines are at a 90 degree angle to the handle as is the blade of a hoe. In larger plots, the plow can serve as the most expeditious implement for unearthing potatoes. Commercial harvesting is typically done with large potato harvesters which scoop up the plant and the surrounding earth. This is transported up an apron chain consisting of steel links several feet wide, which separates some of the dirt. The chain deposits into an area where further separation occurs. Different designs employ different systems at this point. The most complex designs use vine choppers and shakers, along with a blower system or "Flying Willard" to separate the potatoes from the plant. The result is then usually run past workers who continue to sort out plant material, stones, and rotten potatoes before the potatoes are continuously delivered to a wagon or truck. Further inspection and separation occurs when the potatoes are unloaded from the field vehicles and put into storage. Correct potato husbandry is an arduous task in the best of circumstances. Good ground preparation, harrowing, plowing, and rolling are always needed, along with a little grace from the weather and a good source of water. Three successive plowings, with associated harrowing and rolling, are desirable before planting. Eliminating all root-weeds is desirable in potato cultivation. Potatoes are the most fruitful of the root crops, but much care and consideration is needed to keep them satisfied and fruitful. It is important to harvest potatoes before heavy frosts begin, since field frost damages potatoes in the ground, and even cold weather makes potatoes more susceptible to bruising and possibly later rotting which can quickly ruin a large stored crop. Seed potato crops are 'rogued' in some countries to eliminate diseased plants or those of a different variety from the seed crop. Storage facilities need to be carefully designed to keep the potatoes alive and slow the natural process of decomposition, which involves the breakdown of starch. It is crucial that the storage area is dark, well ventilated and for long-term storage maintained at temperatures near 40°F (4°C). For short-term storage prior to cooking, temperatures of about 45-50°F (7-10°C) are preferred. Temperatures below 40°F (4°C) convert potatoes' starch into sugar, which alters their taste and cooking qualities and leads to higher acrylamide levels in the cooked product, especially in deep-fried dishes. Under optimum conditions possible in commercial warehouses, potatoes can be stored for up to six months, but several weeks is the normal shelf life in homes. If potatoes develop green areas or start to sprout, these areas should be trimmed before using. FAO reports that the world production of potatoes in 2005 was 319 million tonnes. The largest producer, China, accounted for one-fourth of the global output followed by Russia and India. ## Varieties Potatoes have been bred into many standard or well-known varieties, each of which have particular agricultural or culinary attributes. Varieties are generally categorized into a few main groups, such as Russets, Reds, Whites, Yellows (aka Yukons), and Purples based on common characteristics. Popular varieties found in markets may include: - Désirée - King Edward - Kipfler - New - Nicola - Pink Eye - Pink Fir Apple - Red Pontiac - Russet Burbank - Spunta Genetic research on the potato has resulted in at least one genetically-modified variety, the New Leaf, owned by Monsanto corporation. Potatoes of all varieties are generally cured after harvest to thicken the skin. Prior to curing, the skin is very thin and delicate. These potatoes are sometimes sold as "New Potatoes" and are particularly flavorful. New potatoes are often harvested by the home gardener or farmer by "grabbling", i.e. pulling out the young tubers by hand while leaving the plant in place. In additions, markets may sometimes present various thin-skinned potato varieties as "new potatoes". Some horticulturists sell chimeras, made by grafting a tomato plant onto a potato plant, producing both edible tomatoes and potatoes. This practice is not very widespread. ### Philippines On September 22, 2007, Benguet State University (BSU) announce that 4 potato varieties -- Igorota, Solibao, Ganza and a 4th one yet to be given an official tag -- possess more than 18% dry matter content required by fast-food chains to make crispy and sturdy French fries. ## Pests A major pest of potato plants is the Colorado potato beetle. The potato root nematode is a microscopic worm that thrives on the roots, thus causing the potato plants to wilt. Since its eggs can survive in the soil for several years, crop rotation is recommended. Other pests include Aphids, both the Green Peach Aphid and the Potato Aphid. Beetleafhoppers, Thrips, and Mites are also very common potato insect pests. A major disease of potato plants is potato blight caused by Phytophthora infestans. Other major diseases include Rhizoctonia, Sclerotinia, Black Leg, Powdery Mildew, Powdery Scab, Leafroll Virus, Purple Top, and others. # Potatoes and Art The potato has been an essential crop in the Andes since the pre-Columbian Era. The Moche culture from Northern Peru made ceramics from earth, water, and fire. This pottery was a sacred substance, formed in significant shapes and used to represent important themes. Potatoes are represented anthropomorphically as well as naturally. Maine companies are exploring the possibilities of using waste potatoes to obtain polylactic acid for use in plastic products.	Potato The potato is the term which applies either to the starchy tuberous crop from the perennial plant Solanum tuberosum of the Solanaceae, or nightshade, family, or to the plant itself. They are the world's most widely grown tuber crop, and the fourth largest food crop in terms of fresh produce — after rice, wheat, and maize ('corn'). Potatoes originated in the area of modern day Peru[1] and then spread from South America to Spain and from there to the rest of the world after European colonization in the late 1400s and early 1500s. In the Southern Bolivian town of San Andreas, as many as 300 varieties may be showcased at the town's annual potato festival. [2] They soon became an important food staple and field crop. For instance, the potato was a staple food for sailors in Spanish ships. After the wreck of the Spanish Armada in 1588, Irish coastal villagers rescued potatoes and planted them. In 1845, a fungal disease, Phytophthora infestans, also known as late blight, spread rapidly through the poorer communities of western Ireland, resulting in the Great Irish Famine. Unfortunately the local population had come to rely heavily on the potato and when crops failed, year after year, huge numbers of people died. Others emigrated, largely to the United States, blaming the British government for the situation. The potato is also strongly associated with Idaho, Maine, North Dakota, Prince Edward Island, Ireland, Jersey and Russia because of its large role in the agricultural economy and history of these regions. # Etymology The English word potato comes from Spanish patata, ultimately from Nahuatl potatl, potentially its first name. Bulgarian картоф, as well as Russian картофель and German Kartoffel, derive from the Italian word tartufoli, which was given to potato because of its similarity to truffles (Italian: tartufo). Another common name is "ground apple": pomme de terre in French, aardappel in Dutch, תפוח אדמה in Hebrew (often written just as פוד), and Erdapfel in Austrian German. An analogous name is Finnish as peruna, which comes from the old Swedish term jordpäron "earth pear". In 16th century French, pomme meant "fruit", thus pomme de terre meant "ground fruit" and was probably literally loan translated to other languages when potatoes were introduced. In Polish potato is called just ziemniaki, and in Slovak zemiak, from the word for "ground". In several northern Indian languages and in Nepali the potato is called alu and in Indonesian kentang. Different names for the potato developed in China's various regions, the most widely used names in standard Chinese today are "horse-bell yam" (马铃薯 - mǎlíngshǔ), "earth bean" (土豆 - tǔdòu), and "foreign taro" (洋芋 - yángyù). # Description Potato plants grow high to the ground and bear yellow to silver flowers with yellow stamens. Potatoes are cross-pollinated mostly by bumblebees that carry pollen from other potato plants, but a substantial amount of self-fertilizing occurs as well. Any potato variety can also be propagated vegetatively by planting tubers, pieces of tubers, cut to include at least one or two eyes, or also by cuttings, a practice used in greenhouses for the production of healthy seed tubers. Some commercial potato varieties do not produce seeds at all (they bear imperfect flowers) and are propagated only from tuber pieces. Confusingly, these tubers or tuber pieces are called "seed potatoes". After potato plants flower, some varieties will produce small green fruits that resemble green cherry tomatoes. Each fruit can contain up to 300 true seeds. One can separate seeds from the fruits by putting them in a blender on a slow speed with some water, then leaving them in water for a day so that the seeds will sink and the rest of the fruit will float. All new potato varieties are grown from seeds, also called "true seed" or "botanical seed" to distinguish it from seed tubers. # Origin and history There is general agreement among contemporary botanists that the potato originated in the Andes, all the way from Colombia to northern Argentina, but with a concentration of genetic diversity, both in the form of cultivated and wild species, in the area of modern day Peru. The potatoes cultivated in the Andes are not all the same species. The major species is Solanum tuberosum ssp. andigena (a tetraploid with 48 chromosomes,) then there are four diploid species (with 24 chromosomes) by the names of Solanum stenotomum, Solanum phureja, Solanum goniocalyx and Solanum ajanhuiri. There are two triploid species (with 36 chromosomes) Solanum chaucha and Solanum juzepczukii, and finally, there is one pentaploid cultivated species (with 60 chromosomes) called Solanum curtilobum. Andean potatoes are adapted to short day conditions and Chilean potatoes to long day conditions. There is sufficient evidence that the tetraploid Andean short day potato was the one that first arrived in Southern Spain in about 1565, from where it spread to the rest of Europe, adapting to European long day conditions in a period of about two hundred years. In order to botanically distinguish potatoes adapted to short days from those thriving and producing tubers under long day conditions, Solanum tuberosum has been split into two subspecies by present-day taxonomists, Solanum tuberosum ssp. tuberosum (adapted to long days) and Solanum tuberosum ssp. andigena (adapted to short days.) Apart from their different photoperiodic reaction, these two subspecies are also distinct morphologically, though the differences are apparent only to an experienced taxonomist. Russian taxonomists did, in fact, create two different species in the early part of the 20th century, Solanum tuberosum and Solanum andigenum, to mark the same distinction. The process of adaptation to long days has happened once before as the potato moved from the Andes to the south of the continent. This was before the Europeans arrived in South America. Chile still has a large amount of valuable potato germplasm adapted to long days. Historical and genetic evidence suggests that the potato reached India not very much later than Europe, probably taken there by the Portuguese. In isolated areas in the Himalayas of India and Nepal, so called "desi" potatoes are still grown, and they are very similar to the short day adapted modern Andean potato, Solanum tuberosum ssp. andigena. There are about five thousand potato varieties world wide. Three thousand of them are found in the Andes alone, mainly in Peru, Bolivia, Ecuador and Colombia. They belong to eight or nine species, depending on the taxonomic school. Apart from the five thousand cultivated varieties, there are about 200 wild species, many of which can be cross-bred with cultivated species, which has been done repeatedly to transfer resistances to certain pests and diseases from the gene pool of wild species to the gene pool of cultivated potato species. The list of varieties found in European, North American or Asian markets is very limited, and these varieties are all of the same species, Solanum tuberosum ssp. tuberosum. These potatoes are often referred to as "Irish" potatoes in the English speaking world because of their association with the Great Irish Famine, which began in 1845 and lasted for six years. The Irish peasant population had become highly dependent on the potato because of the relatively large amount of food that could be produced on fairly small holdings. Immigrant farmers from the Palatinate region of Germany brought their own crops, such as turnips, to Western Ireland. They were much less dependent on the potato than their native Irish neighbors and were largely spared the effects of the potato famine. The disease killing the Irish potato crop was the late blight fungus Phytophthora infestans. The long lasting aftereffects of this famine are well known and well documented. What is less well known is the role of the British during the potato famine. Rich aristocratic British landowners continued to export grain from Ireland to other parts of the world even as tens of thousands of Irish were dying of starvation. However, there were some British owned estates where not one Irish peasant starved during the famine. Authors like Salaman have written in detail about that situation, which has also been recognized by contemporary British historians. Most modern potatoes grown in North America arrived through European settlement and not independently from the South American sources. Still, one wild potato species, Solanum fendleri, is found as far north as Texas and used in breeding for resistance to a nematode species attacking cultivated potatoes. A secondary center of genetic variability of the potato is Mexico, where important wild species are found that have been used extensively in modern breeding, such as the hexaploid Solanum demissum, as a source of resistance to the devastating late blight disease. The potato became an important staple crop in northern Europe as the climate changed due to the Little Ice Age, when traditional crops in this region did not produce as reliably as before. At times when and where most other crops would fail, potatoes could still typically be relied upon to contribute adequately to food supplies during the colder years. The potato was not popular in France during this time, and it is believed that some of the infamous famines could have been lessened if French farmers had adopted it. Today, the potato forms an important part of the traditional cuisine of the British Isles, northern Europe, central Europe and eastern Europe. As of 2007, Germany has a higher consumption of potato per capita than any other country. # Nutrition Template:Nutritionalvalue Nutritionally, potatoes are best known for their carbohydrate content (approximately 26 grams in a medium potato). Starch is the predominant form of carbohydrate found in potatoes. A small but significant portion of the starch in potatoes is resistant to enzymatic digestion in the stomach and small intestine and, thus, reaches the large intestine essentially intact. This resistant starch is considered to have similar physiological effects and health benefits of fiber (e.g., provide bulk, offer protection against colon cancer, improve glucose tolerance and insulin sensitivity, lower plasma cholesterol and triglyceride concentrations, increase satiety, and possibly even reduce fat storage) (Cummings et al. 1996; Hylla et al 1998; Raban et al. 1994). The amount of resistant starch found in potatoes is highly dependent upon preparation methods. Cooking and then cooling potatoes significantly increases resistant starch. For example, cooked potato starch contains about 7% resistant starch, which increases to about 13% upon cooling (Englyst et al. 1992). Potatoes contain a number of important vitamins and minerals. A medium potato (150g/5.3 oz) with the skin provides 27 mg vitamin C (45% of the Daily Value (DV)), 620 mg of potassium (18% of DV), 0.2 mg vitamin B6 (10% of DV) and trace amounts of thiamin, riboflavin, folate, niacin, magnesium, phosphorus, iron, and zinc. Moreover, the fiber content of a potato with skin (2 grams) equals that of many whole grain breads, pastas, and cereals. In addition to vitamins, minerals and fiber, potatoes also contain an assortment of phytochemicals, such as carotenoids and polyphenols. The notion that “all of the potato’s nutrients” are found in the skin is an urban legend. While the skin does contain approximately half of the total dietary fiber, the majority (more than 50%) of the nutrients are found within the potato itself. The cooking method used can significantly impact the nutrient availability of the potato. New and fingerling potatoes offer the advantage that they contain fewer toxic chemicals. Such potatoes offer an excellent source of nutrition. Peeled, long-stored potatoes have less nutritional value, although they still have potassium and vitamin B. Potatoes are often broadly classified as “high” on the glycemic index (GI) and thus are frequently excluded from the diets of individuals trying to follow a “low GI” eating regimen. In fact, the GI of potatoes can vary considerably depending on the type (i.e., red vs. russet vs. white vs. Prince Edward), origin (i.e., where it was grown), preparation methods (i.e., cooking method, whether it is eaten hot or cold, whether it is mashed or cubed or consumed whole, etc), and what it is consumed with (i.e., the addition of various high fat or high protein toppings) (Fernandes et al. 2006). Potatoes are prepared in many ways: skin-on or peeled, whole or cut up, with seasonings or without. The only requirement involves cooking to break down the starch. Most potato dishes are served hot, but some are first cooked then served cold, notably potato salad and potato chips/crisps. Common dishes are: mashed potatoes, which are first boiled (usually peeled), and then mashed with milk or yogurt and butter; whole baked potatoes; boiled or steamed potatoes; French-fried potatoes or chips; cut into cubes and roasted; scalloped, diced, or sliced and fried (home fries); grated into small thin strips and fried (hash browns); grated and formed into dumplings, Rösti or potato pancakes. Unlike many foods, potatoes can also be easily cooked in a microwave oven and still retain nearly all of their nutritional value, provided that they are covered in ventilated plastic wrap to prevent moisture from escaping—this method produces a meal very similar to a steamed potato while retaining the appearance of a conventionally baked potato. Potato chunks also commonly appear as a stew ingredient. Potatoes are boiled between 10 and 25[3] minutes, depending on size and type, to become soft. # Regional dishes ## Latin America Peruvian Cuisine naturally contains the potato as a primary ingredient in many dishes, as around 3,000 varieties of this tuber are grown there.[4] Some of the more famous dishes include Papa a la huancaina, Papa rellena, Ocopa, Carapulcra, Causa and Cau Cau among many others. ## Europe Mashed potatoes form a major component of several traditional dishes from the British Isles such as shepherd's pie, bubble and squeak, champ and the 'mashit tatties' (Scots language) which accompany haggis. They are also often sautéed to accompany a meal. Colcannon is a traditional Irish dish involving mashed potato combined with shredded cabbage and onion. Boxty pancakes are eaten all over Ireland, although associated especially with the north, and in Irish diaspora communities: they are traditionally made with grated potatoes, soaked to loosen the starch and mixed with flour, buttermilk and baking powder. A variant eaten and sold in Lancashire, especially Liverpool, is made with cooked and mashed potatoes. In Northern Europe, especially Denmark, Sweden and Finland, newly harvested, early ripening varieties are considered a special delicacy. Boiled whole and served with dill, these "new potatoes" are traditionally consumed together with Baltic herring. In the UK, new potatoes are cooked with mint and served with a little melted butter - Jersey Royal potatoes are the most prized new potatoes, and have their own Protected Designation of Origin. Potatoes are very popular in continental Europe as well. In Italy, they serve to make a type of pasta called gnocchi. Similarly, cooked and mashed potatoes or potato flour can be used in the knödel or dumpling eaten with or added to meat dishes all over central and Eastern Europe, but especially in Bavaria and Luxembourg. Potatoes form one of the main ingredients in many soups such as the pseudo-French vichyssoise and Albanian potato and cabbage soup. In western Norway, komle is popular. A traditional Canary Islands dish is Canarian wrinkly potatoes or Papas arrugadas. Patatas bravas, a dish of fried potatoes in a spicy tomato sauce, is a near-universal constituent of Spanish tapas. ## North America In the United States, potatoes have become one of the most widely consumed crops, and thus have a variety of preparation methods and condiments. One popular favorite involves a baked potato with cheddar cheese (or sour cream and chives) on top, and in New England "smashed potatoes" (a chunkier variation on mashed potatoes, retaining the peel) have great popularity. Potato flakes are popular as an instant variety of mashed potatoes, which reconstitute into mashed potatoes by adding water, plus butter & salt for taste. A regional dish of Central New York, salt potatoes are bite-sized new potatoes boiled in water saturated with salt then served with melted butter. A traditional Acadian dish from New Brunswick is known as poutine râpée. The Acadian poutine is a ball of grated and mashed potato, salted, sometimes filled with pork in the center, and boiled. The result is a moist ball about the size of a baseball. It is commonly eaten with salt and pepper or brown sugar. It is believed to have originated from the German Klöße, prepared by early German settlers who lived among the Acadians. Poutine, by contrast, is a hearty serving of french fries, fresh cheese curds and hot gravy. Tracing its origins to Quebec in the 1950s, it has become popular across Canada and can usually be found where Canadians gather abroad. # Toxic compounds in potatoes Potatoes contain glycoalkaloids, toxic compounds, of which the most prevalent are solanine and chaconine. Cooking at high temperatures (over 170 °C or 340 °F) partly destroys these. The concentration of glycoalkaloid in wild potatoes suffices to produce toxic effects in humans. Glycoalkaloids occur in the greatest concentrations just underneath the skin of the tuber, and they increase with age and exposure to light. Glycoalkaloids may cause headaches, diarrhea, cramps and in severe cases coma and death; however, poisoning from potatoes occurs very rarely. Light exposure also causes greening, thus giving a visual clue as to areas of the tuber that may have become more toxic; however, this does not provide a definitive guide, as greening and glycoalkaloid accumulation can occur independently of each other. Some varieties of potato contain greater glycoalkaloid concentrations than others; breeders developing new varieties test for this, and sometimes have to discard an otherwise promising cultivar. Breeders try to keep solanine levels below 200 mg/kg (200 ppmw). However, when these commercial varieties turn green, even they can approach concentrations of solanine of 1000 mg/kg (1000 ppmw). In normal potatoes though, analysis has shown solanine levels may be as little as 3.5% of the breeders' maximum, with 7–187 mg/kg being found.[5] The National Toxicology Program suggests that the average American consumes at most 12.5 mg/person/day of solanine from potatoes (note that the toxic dose is actually several times this, depending on body weight). Dr. Douglas L. Holt, the State Extension Specialist for Food Safety at the University of Missouri - Columbia, notes that no reported cases of potato-source solanine poisoning have occurred in the U.S. in the last 50 years and most cases involved eating green potatoes or drinking potato-leaf tea. Solanine is also found in other plants, mainly in the mostly-deadly nightshade family, which includes a minority of edible plants including the potato and the tomato, and other typically more dangerous plants like tobacco. This poison affects the nervous system causing weakness and confusion. - Solanine - List of poisonous plants - Sites with information about the safety of green potatoes: http://www.straightdope.com/classics/a2_055b.html http://www.foodscience.afisc.csiro.au/spuds.htm http://www.promolux.com/english/retail_produce_greening.html - http://www.straightdope.com/classics/a2_055b.html - http://www.foodscience.afisc.csiro.au/spuds.htm - http://www.promolux.com/english/retail_produce_greening.html # Cultivation Potatoes are generally grown from the eyes of another potato and not from seed. Home gardeners often plant a piece of potato with two or three eyes in a hill of mounded soil. Commercial growers plant potatoes as a row crop using seed tubers, young plants or microtubers and may mound the entire row. At harvest time, gardeners generally dig up potatoes with a long-handled, three-prong "grape" (or graip), i.e. a spading fork, or a potato hook which is similar to the graip, except the tines are at a 90 degree angle to the handle as is the blade of a hoe. In larger plots, the plow can serve as the most expeditious implement for unearthing potatoes. Commercial harvesting is typically done with large potato harvesters which scoop up the plant and the surrounding earth. This is transported up an apron chain consisting of steel links several feet wide, which separates some of the dirt. The chain deposits into an area where further separation occurs. Different designs employ different systems at this point. The most complex designs use vine choppers and shakers, along with a blower system or "Flying Willard" to separate the potatoes from the plant. The result is then usually run past workers who continue to sort out plant material, stones, and rotten potatoes before the potatoes are continuously delivered to a wagon or truck. Further inspection and separation occurs when the potatoes are unloaded from the field vehicles and put into storage. Correct potato husbandry is an arduous task in the best of circumstances. Good ground preparation, harrowing, plowing, and rolling are always needed, along with a little grace from the weather and a good source of water. Three successive plowings, with associated harrowing and rolling, are desirable before planting. Eliminating all root-weeds is desirable in potato cultivation. Potatoes are the most fruitful of the root crops, but much care and consideration is needed to keep them satisfied and fruitful. It is important to harvest potatoes before heavy frosts begin, since field frost damages potatoes in the ground, and even cold weather makes potatoes more susceptible to bruising and possibly later rotting which can quickly ruin a large stored crop. Seed potato crops are 'rogued' in some countries to eliminate diseased plants or those of a different variety from the seed crop. Storage facilities need to be carefully designed to keep the potatoes alive and slow the natural process of decomposition, which involves the breakdown of starch. It is crucial that the storage area is dark, well ventilated and for long-term storage maintained at temperatures near 40°F (4°C). For short-term storage prior to cooking, temperatures of about 45-50°F (7-10°C) are preferred.[6] Temperatures below 40°F (4°C) convert potatoes' starch into sugar, which alters their taste and cooking qualities and leads to higher acrylamide levels in the cooked product, especially in deep-fried dishes. Under optimum conditions possible in commercial warehouses, potatoes can be stored for up to six months, but several weeks is the normal shelf life in homes.[6] If potatoes develop green areas or start to sprout, these areas should be trimmed before using.[6] FAO reports that the world production of potatoes in 2005 was 319 million tonnes. The largest producer, China, accounted for one-fourth of the global output followed by Russia and India. ## Varieties Potatoes have been bred into many standard or well-known varieties, each of which have particular agricultural or culinary attributes. Varieties are generally categorized into a few main groups, such as Russets, Reds, Whites, Yellows (aka Yukons), and Purples based on common characteristics. Popular varieties found in markets may include: - Désirée - King Edward - Kipfler - New - Nicola - Pink Eye - Pink Fir Apple - Red Pontiac - Russet Burbank - Spunta Genetic research on the potato has resulted in at least one genetically-modified variety, the New Leaf, owned by Monsanto corporation. Potatoes of all varieties are generally cured after harvest to thicken the skin. Prior to curing, the skin is very thin and delicate. These potatoes are sometimes sold as "New Potatoes" and are particularly flavorful. New potatoes are often harvested by the home gardener or farmer by "grabbling", i.e. pulling out the young tubers by hand while leaving the plant in place. In additions, markets may sometimes present various thin-skinned potato varieties as "new potatoes". Some horticulturists sell chimeras, made by grafting a tomato plant onto a potato plant, producing both edible tomatoes and potatoes. This practice is not very widespread. ### Philippines On September 22, 2007, Benguet State University (BSU) announce that 4 potato varieties -- Igorota, Solibao, Ganza and a 4th one yet to be given an official tag -- possess more than 18% dry matter content required by fast-food chains to make crispy and sturdy French fries.[7] ## Pests A major pest of potato plants is the Colorado potato beetle. The potato root nematode is a microscopic worm that thrives on the roots, thus causing the potato plants to wilt. Since its eggs can survive in the soil for several years, crop rotation is recommended. Other pests include Aphids, both the Green Peach Aphid and the Potato Aphid. Beetleafhoppers, Thrips, and Mites are also very common potato insect pests. A major disease of potato plants is potato blight caused by Phytophthora infestans. Other major diseases include Rhizoctonia, Sclerotinia, Black Leg, Powdery Mildew, Powdery Scab, Leafroll Virus, Purple Top, and others. # Potatoes and Art The potato has been an essential crop in the Andes since the pre-Columbian Era. The Moche culture from Northern Peru made ceramics from earth, water, and fire. This pottery was a sacred substance, formed in significant shapes and used to represent important themes. Potatoes are represented anthropomorphically as well as naturally.[8] Maine companies are exploring the possibilities of using waste potatoes to obtain polylactic acid for use in plastic products.	https://www.wikidoc.org/index.php/Potato
10fb1448cabb19712adae9411c77244715d3f5e3	wikidoc	Probit	Probit In probability theory and statistics, the probit function is the inverse cumulative distribution function (CDF), or quantile function associated with the standard normal distribution. It has applications in exploratory statistical graphics and specialized regression modeling of binary response variables. For the standard normal distribution (often denoted N(0,1)), the CDF is commonly denoted \Phi(z). \Phi(z) is a continuous, monotone increasing sigmoid function whose domain is the real line and range is (0,1). As an example, consider the familiar fact that the N(0,1) distribution places 95% of probability between -1.96 and 1.96, and is symmetric around zero. It follows that The probit function gives the 'inverse' computation, generating a value of an N(0,1) random variable, associated with specified cumulative probability. Formally, the probit function is the inverse of \Phi(z), denoted \Phi^{-1}(p). Continuing the example, In general, The idea of probit was published in 1934 by Chester Ittner Bliss (1899-1979) in an article in Science on how to treat data such as the percentage of a pest killed by a pesticide. Bliss proposed transforming the percentage killed into a "probability unit" (or "probit") which was linearly related to the modern definition (he defined it arbitrarily as equal to 0 for 0.0001 and 10 for 0.9999). He included a table to aid other researchers to convert their kill percentages to his probit, which they could then plot against the logarithm of the dose and thereby, it was hoped, obtain a more or less straight line. Such a so-called probit model is still important in toxicology, as well as other fields. The approach is justified in particular if response variation can be rationalized as a lognormal distribution of tolerances among subjects on test, where the tolerance of a particular subject is the dose just sufficient for the response of interest. The table introduced by Bliss was carried forward in an important text on toxicological applications by D. J. Finney. Values tabled by Bliss can be derived from probits as defined here by adding a value of 5. This distinction is summarized by Collett (p. 55): "The original definition of a probit primarily to avoid having to work with negative probits; ... This definition is still used in some quarters, but in the major statistical software packages for what is referred to as probit analysis, probits are defined without the addition of 5." It should be observed that probit methodology, including numerical optimization for fitting of probit functions, was introduced before widespread availability of electronic computing. When using tables, it was convenient to have probits uniformly positive. Common areas of application do not require positive probits. # Diagnosing deviation of a distribution from normality In addition to providing a basis for important types of regression, the probit function is useful in statistical analysis for diagnosing deviation from normality, according to the method of Q-Q plotting. If a set of data is actually a sample of a normal distribution, a plot of the values against their probit scores will be approximately linear. Specific deviations from normality such as asymmetry, heavy tails, or bimodality can be diagnosed based on detection of specific deviations from linearity. While the Q-Q plot can be used for comparison to any distribution family (not only the normal), the normal Q-Q plot is a relatively standard exploratory data analysis procedure because the assumption of normality is often a starting point for analysis. # Computation The normal distribution CDF and its inverse are not available in closed form, and computation requires careful use of numerical procedures. However, the functions are widely available in software for statistics and probability modeling, and in spreadsheets. In computing environments where numerical implementations of the inverse error function are available, the probit function may be obtained as \operatorname{probit}(p) = \sqrt{2}\,\operatorname{erf}^{-1}(2p-1). An example is MATLAB, where an 'erfinv' function is available. The language Mathematica implements 'InverseErf'. Other environments directly implement the probit function as is shown in the following session in the R programming language. qnorm(0.025) pnorm(-1.96) ## An ordinary differential equation for the probit function Another means of computation is based on forming a non-linear ordinary differential equation for probit. Abbreviating the probit function as w(p), the ODE is with the centre (boundary) conditions This equation may be solved by several methods, including the classical power series approach. From this solutions of arbitrarily high accuracy may be developed based on Steinbrecher's approach to the series for the inverse error function. The power series solution is given by where the coefficients d_k satisfy the non-linear recurrence with d_0=1 . In this form the ratio d_{k+1}/d_k \rightarrow 1 as k \rightarrow \infty . # Related topics Closely related to the probit function (and probit model) are the logit function and logit model. The inverse of the logistic function is given by Analogously to the probit model, we may assume that such a quantity is related linearly to a set of predictors, resulting in the logit model, the basis in particular of logistic regression model, the most prevalent form of regression analysis for binary response data. In current statistical practice, probit and logit regression models are often handled as cases of the generalized linear model.	Probit In probability theory and statistics, the probit function is the inverse cumulative distribution function (CDF), or quantile function associated with the standard normal distribution. It has applications in exploratory statistical graphics and specialized regression modeling of binary response variables. For the standard normal distribution (often denoted N(0,1)), the CDF is commonly denoted <math>\Phi(z)</math>. <math>\Phi(z)</math> is a continuous, monotone increasing sigmoid function whose domain is the real line and range is (0,1). As an example, consider the familiar fact that the N(0,1) distribution places 95% of probability between -1.96 and 1.96, and is symmetric around zero. It follows that The probit function gives the 'inverse' computation, generating a value of an N(0,1) random variable, associated with specified cumulative probability. Formally, the probit function is the inverse of <math>\Phi(z)</math>, denoted <math>\Phi^{-1}(p)</math>. Continuing the example, In general, The idea of probit was published in 1934 by Chester Ittner Bliss (1899-1979) in an article in Science on how to treat data such as the percentage of a pest killed by a pesticide.[1] Bliss proposed transforming the percentage killed into a "probability unit" (or "probit") which was linearly related to the modern definition (he defined it arbitrarily as equal to 0 for 0.0001 and 10 for 0.9999). He included a table to aid other researchers to convert their kill percentages to his probit, which they could then plot against the logarithm of the dose and thereby, it was hoped, obtain a more or less straight line. Such a so-called probit model is still important in toxicology, as well as other fields. The approach is justified in particular if response variation can be rationalized as a lognormal distribution of tolerances among subjects on test, where the tolerance of a particular subject is the dose just sufficient for the response of interest. The table introduced by Bliss was carried forward in an important text on toxicological applications by D. J. Finney.[2][3] Values tabled by Bliss can be derived from probits as defined here by adding a value of 5. This distinction is summarized by Collett (p. 55):[4] "The original definition of a probit [with 5 added was] primarily to avoid having to work with negative probits; ... This definition is still used in some quarters, but in the major statistical software packages for what is referred to as probit analysis, probits are defined without the addition of 5." It should be observed that probit methodology, including numerical optimization for fitting of probit functions, was introduced before widespread availability of electronic computing. When using tables, it was convenient to have probits uniformly positive. Common areas of application do not require positive probits. # Diagnosing deviation of a distribution from normality In addition to providing a basis for important types of regression, the probit function is useful in statistical analysis for diagnosing deviation from normality, according to the method of Q-Q plotting. If a set of data is actually a sample of a normal distribution, a plot of the values against their probit scores will be approximately linear. Specific deviations from normality such as asymmetry, heavy tails, or bimodality can be diagnosed based on detection of specific deviations from linearity. While the Q-Q plot can be used for comparison to any distribution family (not only the normal), the normal Q-Q plot is a relatively standard exploratory data analysis procedure because the assumption of normality is often a starting point for analysis. # Computation The normal distribution CDF and its inverse are not available in closed form, and computation requires careful use of numerical procedures. However, the functions are widely available in software for statistics and probability modeling, and in spreadsheets. In computing environments where numerical implementations of the inverse error function are available, the probit function may be obtained as \operatorname{probit}(p) = \sqrt{2}\,\operatorname{erf}^{-1}(2p-1). </math> An example is MATLAB, where an 'erfinv' function is available. The language Mathematica implements 'InverseErf'. Other environments directly implement the probit function as is shown in the following session in the R programming language. > qnorm(0.025) [1] -1.959964 > pnorm(-1.96) [1] 0.02499790 ## An ordinary differential equation for the probit function Another means of computation is based on forming a non-linear ordinary differential equation for probit. Abbreviating the probit function as <math>w(p)</math>, the ODE is with the centre (boundary) conditions This equation may be solved by several methods, including the classical power series approach. From this solutions of arbitrarily high accuracy may be developed based on Steinbrecher's approach to the series for the inverse error function[5]. The power series solution is given by where the coefficients <math>d_k </math> satisfy the non-linear recurrence with <math> d_0=1 </math>. In this form the ratio <math>d_{k+1}/d_k \rightarrow 1 </math> as <math>k \rightarrow \infty </math>. # Related topics Closely related to the probit function (and probit model) are the logit function and logit model. The inverse of the logistic function is given by Analogously to the probit model, we may assume that such a quantity is related linearly to a set of predictors, resulting in the logit model, the basis in particular of logistic regression model, the most prevalent form of regression analysis for binary response data. In current statistical practice, probit and logit regression models are often handled as cases of the generalized linear model.	https://www.wikidoc.org/index.php/Probit
7b22245a8cd31d869e6477600cc6fd8983e9f11d	wikidoc	Proton	Proton Please Take Over This Page and Apply to be Editor-In-Chief for this topic: There can be one or more than one Editor-In-Chief. You may also apply to be an Associate Editor-In-Chief of one of the subtopics below. Please mail us to indicate your interest in serving either as an Editor-In-Chief of the entire topic or as an Associate Editor-In-Chief for a subtopic. Please be sure to attach your CV and or biographical sketch. In physics, the proton (Greek πρώτον / proton = first) is a subatomic particle with an electric charge of one positive fundamental unit 1.60217653(14)×10^−19 C, a diameter of about 1.65x10^-15 m , and a mass of (938.27231 MeV/c2) (1.00727646688(13) u), (1.6726x10^-27 kg), or about 1836 times the mass of an electron. # History Ernest Rutherford is generally credited with the discovery of the proton. In 1918 Rutherford noticed that when alpha particles were shot into nitrogen gas, his scintillation detectors showed the signatures of hydrogen nuclei. Rutherford determined that the only place this hydrogen could have come from was the nitrogen, and therefore nitrogen must contain hydrogen nuclei. He thus suggested that the hydrogen nucleus, which was known to have an atomic number of 1, was an elementary particle. Prior to Rutherford, Eugene Goldstein had observed canal rays, which were composed of positively charged ions. After the discovery of the electron by J.J. Thomson, Goldstein suggested that since the atom is electrically neutral there must be a positively charged particle in the atom and tried to discover it. He used the "canal rays" observed to be moving against the electron flow in cathode ray tubes. After the electron had been removed from particles inside the cathode ray tube they became positively charged and moved towards the cathode. Most of the charged particles passed through the cathode, it being perforated, and produced a glow on the glass. At this point, Goldstein believed that he had discovered the proton. When he calculated the ratio of charge to mass of this new particle (which in case of the electron was found to be the same for every gas that was used in the cathode ray tube) was found to be different when the gases used were changed. The reason was simple. What Goldstein assumed to be a proton was actually an ion. He gave up his work there, but promised that "he would return." However, he was widely ignored. # Description Protons are spin −1/2 fermions and are composed of three quarks, making them baryons. The two up quarks and one down quark of the proton are held together by the strong force, mediated by gluons. Protons and neutrons are both nucleons, which may be bound by the nuclear force into atomic nuclei. The nucleus of the most common isotope of the hydrogen atom is a single proton (it contains no neutrons). The nuclei of heavy hydrogen (deuterium and tritium) contain neutrons. All other types atoms are composed of two or more protons and various numbers of neutrons. The number of protons in the nucleus determines the chemical properties of the atom and thus which chemical element is represented; it is the number of both neutrons and protons in a nuclide which determine the particular isotope of an element. # Antiproton The antiparticle of the proton is the antiproton. It was discovered in 1955 by Emilio Segrè and Owen Chamberlain, for which they were awarded the 1959 Nobel Prize in Physics. CPT-symmetry puts strong constraints on the relative properties of particles and antiparticles and, therefore, is open to stringent tests. For example, the charges of the proton and antiproton must sum to exactly zero. This equality has been tested to one part in 10^8. The equality of their masses is also tested to better than one part in 10^8. By holding antiprotons in a Penning trap, the equality of the charge to mass ratio of the proton and the antiproton has been tested to 1 part in 9 x 10^11. The magnetic moment of the antiproton has been measured with error of 8 x 10^-3 nuclear Bohr magnetons, and is found to be equal and opposite to that of the proton. # High-energy physics Due to their stability and large mass (relative to electrons), protons are well suited to use in particle colliders such as the Large Hadron Collider at CERN and the Tevatron at Fermilab. Protons also make up a large majority of the cosmic rays which impinge on the Earth's atmosphere. Such high-energy proton collisions are more complicated to study than electron collisions, due to the composite nature of the proton. Understanding the details of proton structure requires quantum chromodynamics.	Proton Template:Infobox Particle Please Take Over This Page and Apply to be Editor-In-Chief for this topic: There can be one or more than one Editor-In-Chief. You may also apply to be an Associate Editor-In-Chief of one of the subtopics below. Please mail us [1] to indicate your interest in serving either as an Editor-In-Chief of the entire topic or as an Associate Editor-In-Chief for a subtopic. Please be sure to attach your CV and or biographical sketch. In physics, the proton (Greek πρώτον / proton = first) is a subatomic particle with an electric charge of one positive fundamental unit 1.60217653(14)×10^−19 C, a diameter of about 1.65x10^-15 m [1], and a mass of (938.27231 MeV/c2) (1.00727646688(13) u), (1.6726x10^-27 kg), or about 1836 times the mass of an electron. # History Ernest Rutherford is generally credited with the discovery of the proton. In 1918 Rutherford noticed that when alpha particles were shot into nitrogen gas, his scintillation detectors showed the signatures of hydrogen nuclei. Rutherford determined that the only place this hydrogen could have come from was the nitrogen, and therefore nitrogen must contain hydrogen nuclei. He thus suggested that the hydrogen nucleus, which was known to have an atomic number of 1, was an elementary particle. Template:Seealso Prior to Rutherford, Eugene Goldstein had observed canal rays, which were composed of positively charged ions. After the discovery of the electron by J.J. Thomson, Goldstein suggested that since the atom is electrically neutral there must be a positively charged particle in the atom and tried to discover it. He used the "canal rays" observed to be moving against the electron flow in cathode ray tubes. After the electron had been removed from particles inside the cathode ray tube they became positively charged and moved towards the cathode. Most of the charged particles passed through the cathode, it being perforated, and produced a glow on the glass. At this point, Goldstein believed that he had discovered the proton.[2] When he calculated the ratio of charge to mass of this new particle (which in case of the electron was found to be the same for every gas that was used in the cathode ray tube) was found to be different when the gases used were changed. The reason was simple. What Goldstein assumed to be a proton was actually an ion. He gave up his work there, but promised that "he would return." However, he was widely ignored. # Description Protons are spin −1/2 fermions and are composed of three quarks[3], making them baryons. The two up quarks and one down quark of the proton are held together by the strong force, mediated by gluons. Protons and neutrons are both nucleons, which may be bound by the nuclear force into atomic nuclei. The nucleus of the most common isotope of the hydrogen atom is a single proton (it contains no neutrons). The nuclei of heavy hydrogen (deuterium and tritium) contain neutrons. All other types atoms are composed of two or more protons and various numbers of neutrons. The number of protons in the nucleus determines the chemical properties of the atom and thus which chemical element is represented; it is the number of both neutrons and protons in a nuclide which determine the particular isotope of an element. # Antiproton The antiparticle of the proton is the antiproton. It was discovered in 1955 by Emilio Segrè and Owen Chamberlain, for which they were awarded the 1959 Nobel Prize in Physics. CPT-symmetry puts strong constraints on the relative properties of particles and antiparticles and, therefore, is open to stringent tests. For example, the charges of the proton and antiproton must sum to exactly zero. This equality has been tested to one part in 10^8. The equality of their masses is also tested to better than one part in 10^8. By holding antiprotons in a Penning trap, the equality of the charge to mass ratio of the proton and the antiproton has been tested to 1 part in 9 x 10^11. The magnetic moment of the antiproton has been measured with error of 8 x 10^-3 nuclear Bohr magnetons, and is found to be equal and opposite to that of the proton. # High-energy physics Due to their stability and large mass (relative to electrons), protons are well suited to use in particle colliders such as the Large Hadron Collider at CERN and the Tevatron at Fermilab. Protons also make up a large majority of the cosmic rays which impinge on the Earth's atmosphere. Such high-energy proton collisions are more complicated to study than electron collisions, due to the composite nature of the proton. Understanding the details of proton structure requires quantum chromodynamics.	https://www.wikidoc.org/index.php/Proton
b1eb510d1ff940c249e9896a36d15ac01ba2f57e	wikidoc	Pulsus	Pulsus Please Take Over This Page and Apply to be Editor-In-Chief for this topic: There can be one or more than one Editor-In-Chief. You may also apply to be an Associate Editor-In-Chief of one of the subtopics below. Please mail us to indicate your interest in serving either as an Editor-In-Chief of the entire topic or as an Associate Editor-In-Chief for a subtopic. Please be sure to attach your CV and or biographical sketch. There are four separate findings that pulsus may refer to: # Pulsus tardus et parvus Pulsus tardus et parvus also known as Pulsus parvus et tardus, more commonly known as a "slow-rising" or "anacrotic" pulse, is a sign where, upon palpation, the pulse is weak/small (parvus), and late (tardus) relative to contraction of the heart. Classically, it is seen in aortic valve stenosis. With respect to aortic stenosis, "typical findings include a narrow pulse pressure, a harsh late-peaking systolic murmur heard best at the right second intercostal space with radiation to the carotid arteries, and a delayed slow-rising carotid upstroke (pulsus parvus et tardus)." # Pulsus bisferiens Pulsus bisferiens also bisferious pulse or biphasic pulse, is a sign where, on palpation of the pulse, a double peak per cardiac cycle can be appreciated. Bisferious means striking twice. Classically, it is detected when aortic insufficiency exists in association with aortic stenosis, but may also be found in isolated but severe aortic insufficiency, and hypertrophic obstructive cardiomyopathy. # Pulsus bigeminus Pulsus bigeminus is a cardiovascular phenomenon characterized by groups of two heartbeats close together followed by a longer pause. The second pulse is weaker than the first. It is caused by premature contractions, usually of the ventricles, after every other beat. It can be a sign of hypertrophic obstructive cardiomyopathy or of many other types of heart disease. It can also be an innocent and passing phenomenon. # Pulsus paradoxus Pulsus paradoxus (PP), also paradoxic pulse and paradoxical pulse, is an exaggeration of the normal variation in the pulse during the inspiratory phase of respiration, in which the pulse becomes weaker as one inhales and stronger as one exhales. It is a sign that is indicative of several conditions including cardiac tamponade and lung diseases (e.g. asthma, COPD). The paradox in pulsus paradoxus is that, on clinical examination, one can detect extra beats on cardiac auscultation, during inspiration, when compared to the radial pulse. It results from an accentuated decrease of the blood pressure, which leads to the (radial) pulse not being palpable and may be accompanied by an increase in the jugular venous pressure height (Kussmaul sign). As is usual with inspiration, the heart rate is increased, due to increased venous return.	Pulsus Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Please Take Over This Page and Apply to be Editor-In-Chief for this topic: There can be one or more than one Editor-In-Chief. You may also apply to be an Associate Editor-In-Chief of one of the subtopics below. Please mail us [2] to indicate your interest in serving either as an Editor-In-Chief of the entire topic or as an Associate Editor-In-Chief for a subtopic. Please be sure to attach your CV and or biographical sketch. There are four separate findings that pulsus may refer to: ## Pulsus tardus et parvus Pulsus tardus et parvus also known as Pulsus parvus et tardus, more commonly known as a "slow-rising" or "anacrotic" pulse, is a sign where, upon palpation, the pulse is weak/small (parvus), and late (tardus) relative to contraction of the heart. Classically, it is seen in aortic valve stenosis. With respect to aortic stenosis, "typical findings include a narrow pulse pressure, a harsh late-peaking systolic murmur heard best at the right second intercostal space with radiation to the carotid arteries, and a delayed slow-rising carotid upstroke (pulsus parvus et tardus)."[1] ## Pulsus bisferiens Pulsus bisferiens also bisferious pulse or biphasic pulse, is a sign where, on palpation of the pulse, a double peak per cardiac cycle can be appreciated. Bisferious means striking twice. Classically, it is detected when aortic insufficiency exists in association with aortic stenosis, but may also be found in isolated but severe aortic insufficiency, and hypertrophic obstructive cardiomyopathy. ## Pulsus bigeminus Pulsus bigeminus is a cardiovascular phenomenon characterized by groups of two heartbeats close together followed by a longer pause. The second pulse is weaker than the first. It is caused by premature contractions, usually of the ventricles, after every other beat. It can be a sign of hypertrophic obstructive cardiomyopathy or of many other types of heart disease. It can also be an innocent and passing phenomenon. ## Pulsus paradoxus Pulsus paradoxus (PP), also paradoxic pulse and paradoxical pulse, is an exaggeration of the normal variation in the pulse during the inspiratory phase of respiration, in which the pulse becomes weaker as one inhales and stronger as one exhales. It is a sign that is indicative of several conditions including cardiac tamponade and lung diseases (e.g. asthma, COPD).[1] The paradox in pulsus paradoxus is that, on clinical examination, one can detect extra beats on cardiac auscultation, during inspiration, when compared to the radial pulse.[1] It results from an accentuated decrease of the blood pressure, which leads to the (radial) pulse not being palpable and may be accompanied by an increase in the jugular venous pressure height (Kussmaul sign). As is usual with inspiration, the heart rate is increased,[2] due to increased venous return.[3]	https://www.wikidoc.org/index.php/Pulsus
0824385e377b14aeceee05c25f5b848092d675d8	wikidoc	Purell	Purell Purell is an instant hand sanitizer which claims to kill "99.99% of most common germs that may cause illness in as little as 15 seconds." Its active ingredient is ethyl alcohol (62%). It is used by wetting one's hands thoroughly with the product, then briskly rubbing one's hands together until dry. Purell is the most popular hand sanitizer in the U.S. Pfizer acquired the exclusive rights to distribute Purell in the consumer market from GOJO Industries in 2004, and on June 27 2006 Johnson & Johnson announced its acquisition of the Pfizer Consumer Healthcare division, which includes the Purell brand, for $16.6 billion. In 2006, The New York Times reported that Purell is heavily used by politicians during election season, when they have to shake countless hands and remain in robust health. The product is flammable and may discolor fabrics. The inactive ingredients include water, isopropyl alcohol, glycerin, carbomer, fragrance, aminomethyl propanol, propylene glycol, isopropyl myristate, and tocopheryl acetate. # Health Risks The product is labelled as needing to be kept out of the reach of Children. The Chicago Tribune reported that children have become inebriated by ingesting Purell. One child's ingestion of the hand sanitizer caused her blood alcohol level to reach 0.218.	Purell Purell is an instant hand sanitizer which claims to kill "99.99% of most common germs that may cause illness in as little as 15 seconds." Its active ingredient is ethyl alcohol (62%). It is used by wetting one's hands thoroughly with the product, then briskly rubbing one's hands together until dry. Purell is the most popular hand sanitizer in the U.S.[citation needed] Pfizer acquired the exclusive rights to distribute Purell in the consumer market from GOJO Industries in 2004[1], and on June 27 2006 Johnson & Johnson announced its acquisition of the Pfizer Consumer Healthcare division, which includes the Purell brand, for $16.6 billion.[2] In 2006, The New York Times reported that Purell is heavily used by politicians during election season, when they have to shake countless hands and remain in robust health.[3] The product is flammable and may discolor fabrics. The inactive ingredients include water, isopropyl alcohol, glycerin, carbomer, fragrance, aminomethyl propanol, propylene glycol, isopropyl myristate, and tocopheryl acetate. # Health Risks The product is labelled as needing to be kept out of the reach of Children. The Chicago Tribune reported that children have become inebriated by ingesting Purell. One child's ingestion of the hand sanitizer caused her blood alcohol level to reach 0.218. [4]	https://www.wikidoc.org/index.php/Purell
c08ec84c066f09c5e379e5770f194542045b98d9	wikidoc	Pyemia	Pyemia Please Take Over This Page and Apply to be Editor-In-Chief for this topic: There can be one or more than one Editor-In-Chief. You may also apply to be an Associate Editor-In-Chief of one of the subtopics below. Please mail us to indicate your interest in serving either as an Editor-In-Chief of the entire topic or as an Associate Editor-In-Chief for a subtopic. Please be sure to attach your CV and or biographical sketch. Pyaemia (or pyemia) is a type of septicaemia that leads to widespread abscesses and is usually caused by the staphylococcus bacteria. Apart from the distinctive abscesses, pyaemia exhibits the same symptoms as other forms of septicaemia. It was almost universally fatal before the introduction of antibiotics. Sir William Osler included a three-page discussion of pyaemia in his textbook The Principles and Practice of Medicine, published in 1892. He defined pyaemia as follows: "A general disease, characterized by recurring chills and intermittent fever and the formation of abscesses in various parts, all of which result from the contamination of the blood by products arising from a focus contaminated by the bacteria of suppuration." Earlier still, Ignaz Semmelweis included a section entitled "Childbed fever is a variety of pyaemia" in his treatise, The Etiology of Childbed Fever (1861). Jane Grey Swisshelm, in her autobiography entitled Half a Century, describes the treatment of pyaemia in 1862 during the American Civil War.	Pyemia Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Please Take Over This Page and Apply to be Editor-In-Chief for this topic: There can be one or more than one Editor-In-Chief. You may also apply to be an Associate Editor-In-Chief of one of the subtopics below. Please mail us [2] to indicate your interest in serving either as an Editor-In-Chief of the entire topic or as an Associate Editor-In-Chief for a subtopic. Please be sure to attach your CV and or biographical sketch. Pyaemia (or pyemia) is a type of septicaemia that leads to widespread abscesses and is usually caused by the staphylococcus bacteria. Apart from the distinctive abscesses, pyaemia exhibits the same symptoms as other forms of septicaemia. It was almost universally fatal before the introduction of antibiotics. Sir William Osler included a three-page discussion of pyaemia in his textbook The Principles and Practice of Medicine, published in 1892. He defined pyaemia as follows: "A general disease, characterized by recurring chills and intermittent fever and the formation of abscesses in various parts, all of which result from the contamination of the blood by products arising from a focus contaminated by the bacteria of suppuration." Earlier still, Ignaz Semmelweis included a section entitled "Childbed fever is a variety of pyaemia" in his treatise, The Etiology of Childbed Fever (1861). Jane Grey Swisshelm, in her autobiography entitled Half a Century, describes the treatment of pyaemia in 1862 during the American Civil War. Template:SIB Template:WikiDoc Sources	https://www.wikidoc.org/index.php/Pyemia
eab104e3b2d81644c3e31bdba7d322d2927ff086	wikidoc	QRICH1	QRICH1 QRICH1, also known as Glutamine-rich protein 1, is a protein that in humans is encoded by the QRICH1 gene. One notable feature of this protein is that it contains a Caspase Activation Recruitment Domain, also known as a CARD domain. As a result of having this domain, QRICH1 is believed to be involved in apoptotic, inflammatory, and host-immune response pathways. # Gene The QRICH1 gene is 64,363 base pairs long, encoding an mRNA transcript that is 3331 bp in length. QRICH1 is located on chromosome 3p21.31 and contains 11 exons. The genomic sequence begins at base pair 49,057,531 and ends at base pair 49,141,201. # Function The exact function of QRICH1 is not well understood by the scientific community. It is, however, thought to be involved in processes such as inflammation and apoptosis due to the presence of a CARD domain near the beginning of the protein sequence. This protein is predicted to localize to the nucleus and is known to interact with the ATXN1 and ATF7IP proteins shown in the image below. # Protein The glutamine-rich protein 1 is 776 amino acids in length. Glutamine residues are abundant, comprising 109 of the amino acids or 14% of the protein. The protein contains three distinct domains. The first, a CARD domain, is a member of the death fold superfamily and is involved in apoptosis signaling pathways, immune signaling, inflammation, and host-defense mechanisms. The second domain is a glutamine-rich domain which comprises a majority of the protein and is highly conserved among orthologs. The final domain is a Domain of Unknown Function (DUF3504) found near the end of the protein sequence. All three of these domains are well conserved throughout strict orthologs. ## Predicted Features Properties of QRICH1 that were predicted using Bioinformatics tools: - Molecular Weight: 86.5 KDa - Isoelectric Point: 5.59 - Post-translational modification: Multiple phosphorylation sites are reported or predicted. PhosphoSitePlus contains three annotated phosphorylated serines at residues 343, 345, and 659. The NetPhos program on ExPASy predicted 45 phosphorylation sites on multiple serine, threonine, and tyrosine residues. There is one predicted sulfinated tyrosine at amino acid 725. - No predicted Signal Peptide or signal peptide cleavage. - Interacting Proteins: ATXN1, Spinocerebellar ataxia type 1 protein, and ATF7IP, activating transcription factor 7-interacting protein 1. ATXN1 is involved in binding RNA in vitro and may be involved in RNA metabolism. ATF7IP is a recruiter protein that couples transcriptional factors to the general transcription apparatus, thereby modulating transcription regulation and chromatin formation. # Expression QRICH1 is expressed at a high level, 3.3 times the average gene. It is expressed ubiquitously throughout the human body, although EST Profile data reveal that QRICH1 is expressed particularly high in tissues such as the thymus, testis, cerebellar cortex and other areas of the brain, trachea, and in embryonic tissue. Health states such as germ cell tumors, leukemia, lymphoma, and chondrosarcoma have also reported high QRICH1 expression. # Homology ## Orthologs QRICH1 is highly conserved among mammalian orthologs, along with other chordates such as fish, birds, and amphibians. The gene has some conservation among insects, but there were no orthologs found in plants, fungi, or yeast. ## Paralogs QRICH1 has five paralogs all of which encode a zinc finger protein.	QRICH1 QRICH1, also known as Glutamine-rich protein 1, is a protein that in humans is encoded by the QRICH1 gene.[1] One notable feature of this protein is that it contains a Caspase Activation Recruitment Domain, also known as a CARD domain.[2] As a result of having this domain, QRICH1 is believed to be involved in apoptotic, inflammatory, and host-immune response pathways.[3] # Gene The QRICH1 gene is 64,363 base pairs long, encoding an mRNA transcript that is 3331 bp in length.[4] QRICH1 is located on chromosome 3p21.31 and contains 11 exons.[5] The genomic sequence begins at base pair 49,057,531 and ends at base pair 49,141,201.[4] # Function The exact function of QRICH1 is not well understood by the scientific community. It is, however, thought to be involved in processes such as inflammation and apoptosis due to the presence of a CARD domain near the beginning of the protein sequence.[3] This protein is predicted to localize to the nucleus and is known to interact with the ATXN1 and ATF7IP proteins shown in the image below.[7] # Protein The glutamine-rich protein 1 is 776 amino acids in length. Glutamine residues are abundant, comprising 109 of the amino acids or 14% of the protein.[8] The protein contains three distinct domains. The first, a CARD domain, is a member of the death fold superfamily and is involved in apoptosis signaling pathways, immune signaling, inflammation, and host-defense mechanisms.[2] The second domain is a glutamine-rich domain which comprises a majority of the protein and is highly conserved among orthologs.[2] The final domain is a Domain of Unknown Function (DUF3504) found near the end of the protein sequence.[2] All three of these domains are well conserved throughout strict orthologs. ## Predicted Features Properties of QRICH1 that were predicted using Bioinformatics tools: - Molecular Weight: 86.5 KDa[9] - Isoelectric Point: 5.59[10] - Post-translational modification: Multiple phosphorylation sites are reported or predicted. PhosphoSitePlus contains three annotated phosphorylated serines at residues 343, 345, and 659.[11] The NetPhos program on ExPASy predicted 45 phosphorylation sites on multiple serine, threonine, and tyrosine residues.[12] There is one predicted sulfinated tyrosine at amino acid 725.[13] - No predicted Signal Peptide or signal peptide cleavage.[14] - Interacting Proteins: ATXN1, Spinocerebellar ataxia type 1 protein, and ATF7IP, activating transcription factor 7-interacting protein 1.[15] ATXN1 is involved in binding RNA in vitro and may be involved in RNA metabolism.[16] ATF7IP is a recruiter protein that couples transcriptional factors to the general transcription apparatus, thereby modulating transcription regulation and chromatin formation.[17] # Expression QRICH1 is expressed at a high level, 3.3 times the average gene.[18] It is expressed ubiquitously throughout the human body, although EST Profile data reveal that QRICH1 is expressed particularly high in tissues such as the thymus, testis, cerebellar cortex and other areas of the brain, trachea, and in embryonic tissue. Health states such as germ cell tumors, leukemia, lymphoma, and chondrosarcoma have also reported high QRICH1 expression. # Homology ## Orthologs QRICH1 is highly conserved among mammalian orthologs, along with other chordates such as fish, birds, and amphibians. The gene has some conservation among insects, but there were no orthologs found in plants, fungi, or yeast.[19] ## Paralogs QRICH1 has five paralogs all of which encode a zinc finger protein.[20]	https://www.wikidoc.org/index.php/QRICH1
fd2478cab830592461f3562604fd9396782c43b3	wikidoc	QRICH2	QRICH2 Glutamine-rich protein 2 is a protein that in humans is edcoded by the QRICH2 gene on human chromosome 17. The function of QRICH2 protein is mostly unknown, but it has been shown that QRICH2 gene contains a high molecular weight Glutenin domain and an ATPase involved domain. QRICH2 gene is highly expressed in testis, and the subcellular location of QRICH2 protein is in the nucleus. # Gene QRICH2 mRNA is 5411 bp long, and its chromosomal location in human is 17q25.1. QRICH2 mRNA has 19 exons and it contains two main function domains: a high molecular weight Glutenin domain (amino acid 446-979) and an ATPase involved domain (amino acid 1036-1413). QRICH2 locates between UBAL D2 gene and PRPSAP1 gene on chromosome 17. There is no predicted stem loop structure on QRICH2 mRNA because there isn't any complementary RNA sequences. # Protein QRICH2 protein is 1663 amino acids long, and 10.9% of the amino acids are Glutamine (Q). 38% of the QRICH2 protein secondary structure is alpha-helix, 39% is beta-sheet and 13% is turning. The human tissue type with the highest level of QRICH2 expression is testis, and this result is confirmed by the Gene Expression Profile for mouse and dog too. The subcellular location of QRICH2 protein is in the nucleus. QRICH2 is a soluble protein, its average hydrophobicity is -0.5995. QRICH2 protein interact with a number of other proteins including SSSCA1, TSSC1, GAPDH, NUP98 and SNAI1. # Homology ## paralogs FLJ25737 mRNA sequences perfectly match with two regions on the QRICH2 mRNA (bp 3157-4302 on QRICH2 match with bp 1-1146 on FLJ25737, bp 4998-5307 on QRICH2 match with bp 1140-1499 on FLJ25737). However, FLJ25737 locates on chromosome 7 and QRICH2 locates on chromosome 17. ## Orthologs QRICH2 protein has well conserved orthologs in many species. The orthologous protein sequences match very well at the region where the high molecular weight Glutenin domain and ATPase involved domain is. # Function The function of QRICH2 protein is mostly unknown. QRICH2 has been shown to belong to the common expression groups on human chromosome 17. The following genes belonged to the common expression groups on chromosome 17: NCOR1, GFAP, QRICH2, ANAPC11 and PER1. QRICH2 may also be an up-regulated gene involved in cell adhesion and cellular morphogenesis. The high expression of QRICH2 gene in testis may suggest that QRICH2 protein has some functions related to hormone production in males. QRICH2 protein has some sequence similarities with the spermidine/spermine N(1)-acetyl-like protein 1 in several species.	QRICH2 Glutamine-rich protein 2 is a protein that in humans is edcoded by the QRICH2 gene on human chromosome 17.[1][2] The function of QRICH2 protein is mostly unknown, but it has been shown that QRICH2 gene contains a high molecular weight Glutenin domain and an ATPase involved domain.[2] QRICH2 gene is highly expressed in testis,[3] and the subcellular location of QRICH2 protein is in the nucleus.[4] # Gene QRICH2 mRNA is 5411 bp long, and its chromosomal location in human is 17q25.1. QRICH2 mRNA has 19 exons and it contains two main function domains: a high molecular weight Glutenin domain (amino acid 446-979) and an ATPase involved domain (amino acid 1036-1413). QRICH2 locates between UBAL D2 gene and PRPSAP1 gene on chromosome 17.[5] There is no predicted stem loop structure on QRICH2 mRNA because there isn't any complementary RNA sequences.[6] # Protein QRICH2 protein is 1663 amino acids long, and 10.9% of the amino acids are Glutamine (Q). 38% of the QRICH2 protein secondary structure is alpha-helix, 39% is beta-sheet and 13% is turning.[7][8] The human tissue type with the highest level of QRICH2 expression is testis, and this result is confirmed by the Gene Expression Profile for mouse and dog too.[9] The subcellular location of QRICH2 protein is in the nucleus. QRICH2 is a soluble protein, its average hydrophobicity is -0.5995.[10] QRICH2 protein interact with a number of other proteins including SSSCA1, TSSC1, GAPDH, NUP98 and SNAI1.[1] # Homology[11] ## paralogs FLJ25737 mRNA sequences[12] perfectly match with two regions on the QRICH2 mRNA (bp 3157-4302 on QRICH2 match with bp 1-1146 on FLJ25737, bp 4998-5307 on QRICH2 match with bp 1140-1499 on FLJ25737). However, FLJ25737 locates on chromosome 7 and QRICH2 locates on chromosome 17. ## Orthologs QRICH2 protein has well conserved orthologs in many species. The orthologous protein sequences match very well at the region where the high molecular weight Glutenin domain and ATPase involved domain is. # Function The function of QRICH2 protein is mostly unknown. QRICH2 has been shown to belong to the common expression groups on human chromosome 17. The following genes belonged to the common expression groups on chromosome 17:[13] NCOR1, GFAP, QRICH2, ANAPC11 and PER1. QRICH2 may also be an up-regulated gene involved in cell adhesion and cellular morphogenesis.[14] The high expression of QRICH2 gene in testis may suggest that QRICH2 protein has some functions related to hormone production in males. QRICH2 protein has some sequence similarities with the spermidine/spermine N(1)-acetyl-like protein 1 in several species.[11]	https://www.wikidoc.org/index.php/QRICH2
c64d44118dd4a58cef3484f92b0746df4ac7327e	wikidoc	Quartz	Quartz Quartz (from German Template:Audio) is the most abundant mineral in the Earth's continental crust (although feldspar is more common in the world as a whole). It is made up of a lattice of silica (Template:SiliconTemplate:Oxygen) tetrahedra. Quartz has a hardness of 7 on the Mohs scale and a density of 2.65 g/cm³. # Crystal habit Quartz belongs to the rhombohedral crystal system. The ideal crystal shape is a six-sided prism terminating with six-sided pyramids at each end. In nature quartz crystals are often twinned, distorted, or so intergrown with adjacent crystals of quartz or other minerals as to only show part of this shape, or to lack obvious crystal faces altogether and appear massive. Well-formed crystals typically form in a 'bed' that has unconstrained growth into a void, but because the crystals must be attached at the other end to a matrix, only one termination pyramid is present. A quartz geode is such a situation where the void is approximately spherical in shape, lined with a bed of crystals pointing inward. It looks very nice # Varieties Pure quartz is colorless or white, colored varieties include rose quartz, amethyst, smoky quartz, milky quartz, and others. Quartz goes by an array of different names. The most important distinction between types of quartz is that of macrocrystalline (individual crystals visible to the unaided eye) and the microcrystalline or cryptocrystalline varieties (aggregates of crystals visible only under high magnification). Chalcedony is a generic term for cryptocrystalline quartz. The cryptocrystalline varieties are either translucent or mostly opaque, while the transparent varieties tend to be macrocrystalline. Although many of the varietal names historically arose from the color of the mineral, current scientific naming schemes refer primarily to the microstructure of the mineral. Color is a secondary identifier for the cryptocrystalline minerals, although it is a primary identifier for the macrocrystalline varieties. This does not always hold true. - Rose quartz Rose quartz - Milk quartz Milk quartz - Rutilated quartz crystal Rutilated quartz crystal ## Synthetic and artificial treatments Not all varieties of quartz are naturally occurring. Prasiolite, an olive colored material, is produced by heat treatment; natural prasiolite has also been observed in Lower Silesia in Poland. Although citrine occurs naturally, the majority is the result of heat-treated amethyst. Carnelian is widely heat-treated to deepen its color. Due to natural quartz being so often twinned, much of the quartz used in industry is synthesized. Large, flawless and untwinned crystals are produced in an autoclave via the hydrothermal process; emeralds are also synthesized in this fashion. While these are still commonly referred to as quartz, the correct term for this material is silicon dioxide. # Occurrence Quartz occurs in hydrothermal veins and pegmatites. Well-formed crystals may reach several meters in length and weigh hundreds of kilograms. These veins may bear precious metals such as gold or silver, and form the quartz ores sought in mining. Erosion of pegmatites may reveal expansive pockets of crystals, known as "cathedrals." Quartz is a common constituent of granite, sandstone, limestone, and many other igneous, sedimentary, and metamorphic rocks. # Related silica minerals Tridymite and cristobalite are high-temperature polymorphs of SiO2 that occur in high-silica volcanic rocks. Coesite is a denser polymorph of quartz found in some meteorite impact sites and in metamorphic rocks formed at pressures greater than those typical of the Earth's crust. Stishovite is a yet denser and higher-pressure polymorph of quartz found in some meteorite impact sites. Lechatelierite is an amorphous silica glass SiO2 which is formed by lightning strikes in quartz sand. # History The name "quartz" comes from the German "Quarz", which is of Slavic origin (Czech miners called it křemen). Other sources insist the name is from the Saxon word "Querkluftertz", meaning cross-vein ore. Quartz is the most common material identified as the mystical substance maban in Australian Aboriginal mythology. It is found regularly in passage tomb cemeteries in Europe in a burial context, eg. Newgrange or Carrowmore in the Republic of Ireland. The Irish word for quartz is grian cloch, which means 'stone of the sun'. Roman naturalist Pliny the Elder believed quartz to be water ice, permanently frozen after great lengths of time. (The word "crystal" comes from the Greek word for ice.) He supported this idea by saying that quartz is found near glaciers in the Alps, but not on volcanic mountains, and that large quartz crystals were fashioned into spheres to cool the hands. He also knew of the ability of quartz to split light into a spectrum. This idea persisted until at least the 1600s. Nicolas Steno's study of quartz paved the way for modern crystallography. He discovered that no matter how distorted a quartz crystal, the long prism faces always made a perfect 60 degree angle. Charles Sawyer invented the commercial quartz crystal manufacturing process in Cleveland, Ohio, United States. This initiated the transition from mined and cut quartz for electrical appliances to manufactured quartz. Quartz's piezoelectric properties were discovered by Jacques and Pierre Curie in 1880. The quartz oscillator or resonator was first developed by Walter Guyton Cady in 1921 . George Washington Pierce designed and patented quartz crystal oscillators in 1923 . Warren Marrison created the first quartz oscillator clock based on the work of Cady and Pierce in 1927 . Quartz crystals are rotary polar (see rotary polarization) and have the ability to rotate the plane of polarization of light passing through them. They are also highly piezoelectric, becoming polarized with a negative charge on one end and a positive charge on the other when subjected to pressure. They will vibrate if an alternating electric current is applied to them. This proves them to be highly important in commerce for making pressure gauges, oscillators, resonators and watches. # Piezoelectricity Quartz crystals have piezoelectric properties, that is they develop an electric potential upon the application of mechanical stress. An early use of this property of quartz crystals was in phonograph pickups. One of the most common piezoelectric uses of quartz today is as a crystal oscillator. The quartz clock is a familiar device using the mineral. The resonant frequency of a quartz crystal oscillator is changed by mechanically loading it, and this principle is used for very accurate measurements of very small mass changes in the quartz crystal microbalance and in thin-film thickness monitors.	Quartz Template:Infobox mineral Quartz (from German Template:Audio[1]) is the most abundant mineral in the Earth's continental crust (although feldspar is more common in the world as a whole). It is made up of a lattice of silica (Template:SiliconTemplate:Oxygen) tetrahedra. Quartz has a hardness of 7 on the Mohs scale and a density of 2.65 g/cm³. # Crystal habit Quartz belongs to the rhombohedral crystal system. The ideal crystal shape is a six-sided prism terminating with six-sided pyramids at each end. In nature quartz crystals are often twinned, distorted, or so intergrown with adjacent crystals of quartz or other minerals as to only show part of this shape, or to lack obvious crystal faces altogether and appear massive. Well-formed crystals typically form in a 'bed' that has unconstrained growth into a void, but because the crystals must be attached at the other end to a matrix, only one termination pyramid is present. A quartz geode is such a situation where the void is approximately spherical in shape, lined with a bed of crystals pointing inward. It looks very nice # Varieties Pure quartz is colorless or white, colored varieties include rose quartz, amethyst, smoky quartz, milky quartz, and others. Quartz goes by an array of different names. The most important distinction between types of quartz is that of macrocrystalline (individual crystals visible to the unaided eye) and the microcrystalline or cryptocrystalline varieties (aggregates of crystals visible only under high magnification). Chalcedony is a generic term for cryptocrystalline quartz. The cryptocrystalline varieties are either translucent or mostly opaque, while the transparent varieties tend to be macrocrystalline. Although many of the varietal names historically arose from the color of the mineral, current scientific naming schemes refer primarily to the microstructure of the mineral. Color is a secondary identifier for the cryptocrystalline minerals, although it is a primary identifier for the macrocrystalline varieties. This does not always hold true. - Rose quartz Rose quartz - Milk quartz Milk quartz - Rutilated quartz crystal Rutilated quartz crystal ## Synthetic and artificial treatments Not all varieties of quartz are naturally occurring. Prasiolite, an olive colored material, is produced by heat treatment; natural prasiolite has also been observed in Lower Silesia in Poland. Although citrine occurs naturally, the majority is the result of heat-treated amethyst. Carnelian is widely heat-treated to deepen its color. Due to natural quartz being so often twinned, much of the quartz used in industry is synthesized. Large, flawless and untwinned crystals are produced in an autoclave via the hydrothermal process; emeralds are also synthesized in this fashion. While these are still commonly referred to as quartz, the correct term for this material is silicon dioxide. # Occurrence Quartz occurs in hydrothermal veins and pegmatites. Well-formed crystals may reach several meters in length and weigh hundreds of kilograms. These veins may bear precious metals such as gold or silver, and form the quartz ores sought in mining. Erosion of pegmatites may reveal expansive pockets of crystals, known as "cathedrals." Quartz is a common constituent of granite, sandstone, limestone, and many other igneous, sedimentary, and metamorphic rocks. # Related silica minerals Tridymite and cristobalite are high-temperature polymorphs of SiO2 that occur in high-silica volcanic rocks. Coesite is a denser polymorph of quartz found in some meteorite impact sites and in metamorphic rocks formed at pressures greater than those typical of the Earth's crust. Stishovite is a yet denser and higher-pressure polymorph of quartz found in some meteorite impact sites. Lechatelierite is an amorphous silica glass SiO2 which is formed by lightning strikes in quartz sand. # History The name "quartz" comes from the German "Quarz", which is of Slavic origin (Czech miners called it křemen). Other sources insist the name is from the Saxon word "Querkluftertz", meaning cross-vein ore.[2] Quartz is the most common material identified as the mystical substance maban in Australian Aboriginal mythology. It is found regularly in passage tomb cemeteries in Europe in a burial context, eg. Newgrange or Carrowmore in the Republic of Ireland. The Irish word for quartz is grian cloch, which means 'stone of the sun'. Roman naturalist Pliny the Elder believed quartz to be water ice, permanently frozen after great lengths of time. (The word "crystal" comes from the Greek word for ice.) He supported this idea by saying that quartz is found near glaciers in the Alps, but not on volcanic mountains, and that large quartz crystals were fashioned into spheres to cool the hands. He also knew of the ability of quartz to split light into a spectrum. This idea persisted until at least the 1600s. Nicolas Steno's study of quartz paved the way for modern crystallography. He discovered that no matter how distorted a quartz crystal, the long prism faces always made a perfect 60 degree angle. Charles Sawyer invented the commercial quartz crystal manufacturing process in Cleveland, Ohio, United States. This initiated the transition from mined and cut quartz for electrical appliances to manufactured quartz. Quartz's piezoelectric properties were discovered by Jacques and Pierre Curie in 1880. The quartz oscillator or resonator was first developed by Walter Guyton Cady in 1921 [1]. George Washington Pierce designed and patented quartz crystal oscillators in 1923 [2]. Warren Marrison created the first quartz oscillator clock based on the work of Cady and Pierce in 1927 [3]. Quartz crystals are rotary polar (see rotary polarization) and have the ability to rotate the plane of polarization of light passing through them. They are also highly piezoelectric, becoming polarized with a negative charge on one end and a positive charge on the other when subjected to pressure. They will vibrate if an alternating electric current is applied to them. This proves them to be highly important in commerce for making pressure gauges, oscillators, resonators and watches. # Piezoelectricity Quartz crystals have piezoelectric properties, that is they develop an electric potential upon the application of mechanical stress. An early use of this property of quartz crystals was in phonograph pickups. One of the most common piezoelectric uses of quartz today is as a crystal oscillator. The quartz clock is a familiar device using the mineral. The resonant frequency of a quartz crystal oscillator is changed by mechanically loading it, and this principle is used for very accurate measurements of very small mass changes in the quartz crystal microbalance and in thin-film thickness monitors.	https://www.wikidoc.org/index.php/Quartz
4654f0a0fb4e5602e90ba5e65274a2461658a0af	wikidoc	Quench	Quench # Overview A quench refers to a rapid cooling. In polymer chemistry and materials science, quenching is used to prevent low-temperature processes such as phase transformations from occurring by only providing a narrow window of time in which the reaction is both thermodynamically favorable and kinetically accessible. For instance, it can reduce crystallinity and thereby increase toughness of both alloys and plastics (produced through polymerization). In metallurgy, it is most commonly used to harden steel by introducing martensite, in which case the steel must be rapidly cooled through its eutectoid point, the temperature at which austenite becomes unstable. In steel alloyed with metals such as nickel and manganese, the eutectoid temperature becomes much lower, but the kinetic barriers to phase transformation remain the same. This allows quenching to start at a lower temperature, making the process much easier. High speed steel also has added tungsten, which serves to raise kinetic barriers and give the illusion that the material has been cooled more rapidly than it really has. Even cooling such alloys slowly in air has most of the desired effects of quenching. Extremely rapid cooling can prevent the formation of all crystal structure, resulting in amorphous metal or "metallic glass". When an electrical current is flowing through a cryogenic superconductor, a slight temperature rise can cause a loss of superconductivity, which leads to resistive heating and a sudden temperature rise. This phenomenon is also called "quenching" # Role of quenching in scrubbing In pollution scrubbers, sometimes hot exhaust gas is quenched, or cooled by water sprays, before entering the scrubber proper. Hot gases (those above ambient temperature) are often cooled to near the saturation level. If not cooled, the hot gas stream can evaporate a large portion of the scrubbing liquor, adversely affecting collection efficiency and damaging scrubber internal parts. If the gases entering the scrubber are too hot, some liquid droplets may evaporate before they have a chance to contact pollutants in the exhaust stream, and others may evaporate after contact, causing captured particles to become reentrained. In some cases, quenching can actually save money. Cooling the gases reduces the temperature and, therefore, the volume of gases,permitting the use of less expensive construction materials and a smaller scrubber vessel and fan. A quenching system can be as simple as spraying liquid into the duct just preceding the main scrubbing vessel, or it can be a separate chamber (or tower) with its own spray system identical to a spray tower. Quenchers are designed using the same principles as scrubbers. Increasing the gas-liquid contact in them increases their operational efficiency. Small liquid droplets cool the exhaust stream more quickly than large droplets because they evaporate more easily. Therefore, less liquid is required. However, in most scrubbing systems, approximately one-and-a-half to two and- a-half times the theoretical evaporation demand is required to ensure proper cooling (Industrial Gas Cleaning Institute 1975). Evaporation also depends on time; it does not occur instantaneously. Therefore, the quencher should be sized to allow for an adequate exhaust stream residence time. Normal residence times range from 0.15 to 0.25 seconds for gases under 540°C (1000°F) to 0.2 to 0.3 seconds for gases hotter than 540°C (Schifftner 1979). Quenching with recirculated scrubber liquor could potentially reduce overall scrubber performance, since recycled liquid usually contains a high level of suspended and dissolved solids. As the liquid droplets evaporate, these solids could become reentrained in the exhaust gas stream. To help reduce this problem, clean makeup water can be added directly to the quench system rather than adding all makeup water to a common sump.	Quench # Overview A quench refers to a rapid cooling. In polymer chemistry and materials science, quenching is used to prevent low-temperature processes such as phase transformations from occurring by only providing a narrow window of time in which the reaction is both thermodynamically favorable and kinetically accessible. For instance, it can reduce crystallinity and thereby increase toughness of both alloys and plastics (produced through polymerization). In metallurgy, it is most commonly used to harden steel by introducing martensite, in which case the steel must be rapidly cooled through its eutectoid point, the temperature at which austenite becomes unstable. In steel alloyed with metals such as nickel and manganese, the eutectoid temperature becomes much lower, but the kinetic barriers to phase transformation remain the same. This allows quenching to start at a lower temperature, making the process much easier. High speed steel also has added tungsten, which serves to raise kinetic barriers and give the illusion that the material has been cooled more rapidly than it really has. Even cooling such alloys slowly in air has most of the desired effects of quenching. Extremely rapid cooling can prevent the formation of all crystal structure, resulting in amorphous metal or "metallic glass". When an electrical current is flowing through a cryogenic superconductor, a slight temperature rise can cause a loss of superconductivity, which leads to resistive heating and a sudden temperature rise. This phenomenon is also called "quenching" # Role of quenching in scrubbing In pollution scrubbers, sometimes hot exhaust gas is quenched, or cooled by water sprays, before entering the scrubber proper. Hot gases (those above ambient temperature) are often cooled to near the saturation level. If not cooled, the hot gas stream can evaporate a large portion of the scrubbing liquor, adversely affecting collection efficiency and damaging scrubber internal parts. If the gases entering the scrubber are too hot, some liquid droplets may evaporate before they have a chance to contact pollutants in the exhaust stream, and others may evaporate after contact, causing captured particles to become reentrained. In some cases, quenching can actually save money. Cooling the gases reduces the temperature and, therefore, the volume of gases,permitting the use of less expensive construction materials and a smaller scrubber vessel and fan. A quenching system can be as simple as spraying liquid into the duct just preceding the main scrubbing vessel, or it can be a separate chamber (or tower) with its own spray system identical to a spray tower. Quenchers are designed using the same principles as scrubbers. Increasing the gas-liquid contact in them increases their operational efficiency. Small liquid droplets cool the exhaust stream more quickly than large droplets because they evaporate more easily. Therefore, less liquid is required. However, in most scrubbing systems, approximately one-and-a-half to two and- a-half times the theoretical evaporation demand is required to ensure proper cooling (Industrial Gas Cleaning Institute 1975). Evaporation also depends on time; it does not occur instantaneously. Therefore, the quencher should be sized to allow for an adequate exhaust stream residence time. Normal residence times range from 0.15 to 0.25 seconds for gases under 540°C (1000°F) to 0.2 to 0.3 seconds for gases hotter than 540°C (Schifftner 1979). Quenching with recirculated scrubber liquor could potentially reduce overall scrubber performance, since recycled liquid usually contains a high level of suspended and dissolved solids. As the liquid droplets evaporate, these solids could become reentrained in the exhaust gas stream. To help reduce this problem, clean makeup water can be added directly to the quench system rather than adding all makeup water to a common sump. [1]	https://www.wikidoc.org/index.php/Quench

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