Datasets:

HiTZ

/

Multilingual-BioASQ-6B

like 2

Follow

HiTZ zentroa 65

[ "CASQ2 mutations are associated with autosomal recessive catecholaminergic polymorphic ventricular tachycardia (CPVT) and familial hypertrophic cardiomyopathy.", "Mutations in the gene encoding for cardiac calsequestrin, CASQ2, cause a rare but severe form of catecholaminergic polymorphic ventricular tachycardia (CPVT).\nThere is also a publication that links mutations in CASQ2 gene to the disease of hypertrophic cardiomyopathy (HCM)." ]

[ "catecholaminergic polymorphic ventricular tachycardia (CPVT)", "CPVT", "catecholaminergic polymorphic ventricular tachycardia", "familial hypertrophic cardiomyopathy", "HCM", "hypertrophic cardiomyopathy" ]

[ "Recessively inherited CPVT is caused by either missense or null-allele mutations in the cardiac calsequestrin (CASQ2) gene. It was suggested that defects in CASQ2 cause protein deficiency and impair Ca(2+) uptake to the sarcoplasmic reticulum and Ca(2+)-dependent inhibition of ryanodine channels, leading to diastolic Ca(2+) leak, after-depolarizations, and arrhythmia. ", "The autosomal recessive form of CPVT is caused by mutations in the CASQ2 gene. In a consanguineous family, a novel homozygous CASQ2 mutation (p.L77P) was identified in a child with CPVT who required implantation of a cardioverter defibrillator due to episodes of syncope while on medical therapy. ", "Catecholaminergic polymorphic ventricular tachycardia is a familial cardiac arrhythmia that is related to RYR2 or CASQ2 gene mutation.", "Thirteen mutations in the CASQ2 gene have been reported so far in association with CPVT. ", "These data increased significantly the number of CASQ2 mutations described in association with CPVT, revealed the high prevalence of splicing and truncating mutations in this gene and brought new insight regarding the dominant inheritance of the disease. Moreover, our report of the first splicing abnormalities in CASQ2 caused by intronic mutation or synonymous change underlines the absolute necessity to perform extensive molecular analysis for genetic diagnosis and counseling of CPVT.", "Mutations in the human cardiac calsequestrin gene (CASQ2) are linked to catecholaminergic polymorphic ventricular tachycardia (CPVT-2).", "Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a familial cardiac arrhythmia that is related to RYR2 or CASQ2 gene mutation. ", "Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an uncommon heritable disease presenting with syncope or sudden cardiac death. Two genes involved in calcium homeostasis, the ryanodine receptor gene and the calsequestrin 2 (CASQ2) gene, have been implicated in this disease. We describe a young man presenting with exercise-induced syncope, clinically diagnosed as CPVT. Genetic analysis revealed two mutations, p.Y55C (c.164A>G) and p.P308L (c.923C>T), in the CASQ2 gene. ", "A novel heterozygous mutation, F189L, in CASQ2 gene was identified in one family with CPVT.", "Catecholamine-induced polymorphic ventricular tachycardia (CPVT) is a familial disorder caused by cardiac ryanodine receptor type 2 (RyR2) or calsequestrin 2 (CASQ2) gene mutations. ", "We conclude that CPVT-causing CASQ2 missense mutations function as null alleles. ", "The central role of RyR2 dysfunction in CASQ2 deficiency unifies the pathophysiologic mechanism underlying CPVT due to RyR2 or CASQ2 mutations and suggests a therapeutic approach for these inherited cardiac arrhythmias.", "Mutations of the RyR2 gene cause autosomal dominant CPVT, while mutations of the CASQ2 gene may cause an autosomal recessive or dominant form of CPVT. ", "Mutations of two myocardial calcium signaling molecules, ryanodine receptor 2 (RYR2) and calsequestrin 2 (CASQ2), may cause catecholaminergic polymorphic ventricular tachycardia (CPVT), a severe inherited arrhythmic disease manifesting with salvoes of exercise-induced bidirectional and polymorphic tachycardias. ", "These data, combined with our previous findings, show that RYR2 mutations are present in at least 6/16 (38%) of the catecholaminergic polymorphic ventricular tachycardia families, while CASQ2 mutations must be a rare cause of CPVT.", "This report reviews evidence that a missense mutation in the CASQ2 gene is associated with autosomal-recessive CPVT.", "An Australian cohort of 252 unrelated familial hypertrophic cardiomyopathy patients were screened for mutations in the Ca(2+) regulatory genes, sorcin (SRI), calstabin (FKBP1B), calsequestrin (CASQ2), phospholamban (PLN), sarcolipin (SLN), calreticulin (CALR3) and calmodulin (CALM). A total of 17 exonic DNA variants were identified in the 7 Ca(2+) regulatory genes studied, of which 4 were considered of pathogenic significance. Two novel mutations in the CALR3 gene were identified (Lys82Arg, Arg73Gln) and one truncation mutation in the PLN gene (Leu39Ter). A variant was also identified in the CASQ2 gene (Asp63Glu). These four variants were all novel, resulted in changes in conserved amino acids and were not identified in a normal population." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/17655857", "http://www.ncbi.nlm.nih.gov/pubmed/24025405", "http://www.ncbi.nlm.nih.gov/pubmed/22650415", "http://www.ncbi.nlm.nih.gov/pubmed/20302875", "http://www.ncbi.nlm.nih.gov/pubmed/22119737", "http://www.ncbi.nlm.nih.gov/pubmed/21618644", "http://www.ncbi.nlm.nih.gov/pubmed/18684293", "http://www.ncbi.nlm.nih.gov/pubmed/22422768", "http://www.ncbi.nlm.nih.gov/pubmed/22298808", "http://www.ncbi.nlm.nih.gov/pubmed/18543230", "http://www.ncbi.nlm.nih.gov/pubmed/22515980", "http://www.ncbi.nlm.nih.gov/pubmed/22733215", "http://www.ncbi.nlm.nih.gov/pubmed/22421959", "http://www.ncbi.nlm.nih.gov/pubmed/15913575", "http://www.ncbi.nlm.nih.gov/pubmed/22557844", "http://www.ncbi.nlm.nih.gov/pubmed/14571276", "http://www.ncbi.nlm.nih.gov/pubmed/23042908", "http://www.ncbi.nlm.nih.gov/pubmed/23595086", "http://www.ncbi.nlm.nih.gov/pubmed/12732448", "http://www.ncbi.nlm.nih.gov/pubmed/19568611", "http://www.ncbi.nlm.nih.gov/pubmed/17607358" ]

[ { "p": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseasome/associatedGene", "s": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseases/1171", "o": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/genes/CASQ2" }, { "p": "http://www.w3.org/2004/02/skos/core#exactMatch", "s": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseases/1171", "o": "http://www.dbpedia.org/resource/Ventricular_tachycardia" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/genes/CASQ2", "o": "CASQ2" }, { "p": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseasome/name", "s": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseases/1171", "o": "Ventricular_tachycardia" }, { "p": "http://www.w3.org/2004/02/skos/core#exactMatch", "s": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseases/1171", "o": "http://www4.wiwiss.fu-berlin.de/sider/resource/side_effects/C0042514" }, { "p": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseasome/associatedGene", "s": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseases/4133", "o": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/genes/CASQ2" }, { "p": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseasome/name", "s": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseases/4133", "o": "Ventricular tachycardia, stress-induced polymorphic, 604772" }, { "p": "http://purl.uniprot.org/core/encodedBy", "s": "http://purl.uniprot.org/uniprot/B3IYI4", "o": "http://linkedlifedata.com/resource/#_42334959493400D" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_423349594934009", "o": "Calsequestrin" }, { "p": "http://www.w3.org/2004/02/skos/core#prefLabel", "s": "http://linkedlifedata.com/resource/#_42334959493400D", "o": "CASQ2" }, { "p": "http://purl.uniprot.org/core/encodedBy", "s": "http://purl.uniprot.org/uniprot/Q3MHM1", "o": "http://linkedlifedata.com/resource/#_51334D484D310013" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_51334D484D3100E", "o": "Calsequestrin" }, { "p": "http://www.w3.org/2004/02/skos/core#prefLabel", "s": "http://linkedlifedata.com/resource/#_51334D484D310013", "o": "CASQ2" }, { "p": "http://purl.uniprot.org/core/encodedBy", "s": "http://purl.uniprot.org/uniprot/B9EHC7", "o": "http://linkedlifedata.com/resource/#_4239454843370010" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_42394548433700B", "o": "Calsequestrin" }, { "p": "http://www.w3.org/2004/02/skos/core#prefLabel", "s": "http://linkedlifedata.com/resource/#_4239454843370010", "o": "Casq2" }, { "p": "http://purl.uniprot.org/core/encodedBy", "s": "http://purl.uniprot.org/uniprot/Q6DI16", "o": "http://linkedlifedata.com/resource/#_51364449313600F" }, { "p": "http://www.w3.org/2004/02/skos/core#prefLabel", "s": "http://linkedlifedata.com/resource/#_51364449313600F", "o": "casq2" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_51364449313600A", "o": "Calsequestrin" }, { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A12021593", "o": "OMIM" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A12036000", "o": "CALSEQUESTRIN, FAST-TWITCH, CARDIAC MUSCLE" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C1413135", "o": "http://linkedlifedata.com/resource/umls/label/A11694918" }, { "p": "http://linkedlifedata.com/resource/umls/altMetaMap", "s": "http://linkedlifedata.com/resource/umls/id/C1413135", "o": "http://linkedlifedata.com/resource/umls/label/A12036000" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A11694918", "o": "calsequestrin 2 (cardiac muscle)" }, { "p": "http://linkedlifedata.com/resource/umls/altMetaMap", "s": "http://linkedlifedata.com/resource/umls/id/C1413135", "o": "http://linkedlifedata.com/resource/umls/label/A12021594" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C1413135", "o": "http://linkedlifedata.com/resource/umls/label/A12021594" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C1413135", "o": "http://linkedlifedata.com/resource/umls/label/A17706428" }, { "p": "http://linkedlifedata.com/resource/umls/altMetaMap", "s": "http://linkedlifedata.com/resource/umls/id/C1413135", "o": "http://linkedlifedata.com/resource/umls/label/A17753910" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A11656733", "o": "PDIB2" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A12021593", "o": "CALSEQUESTRIN 2" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A17706428", "o": "CASQ2" }, { "p": "http://linkedlifedata.com/resource/umls/prefMetaMap", "s": "http://linkedlifedata.com/resource/umls/id/C1413135", "o": "http://linkedlifedata.com/resource/umls/label/A6899061" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A17753910", "o": "CASQ2 gene" }, { "p": "http://linkedlifedata.com/resource/umls/altMetaMap", "s": "http://linkedlifedata.com/resource/umls/id/C1413135", "o": "http://linkedlifedata.com/resource/umls/label/A12021593" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C1413135", "o": "http://linkedlifedata.com/resource/umls/label/A11656733" }, { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A12021594", "o": "OMIM" }, { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A12036000", "o": "OMIM" }, { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A11656733", "o": "HUGO" }, { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A11694918", "o": "HUGO" }, { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A17706428", "o": "HUGO" }, { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A17753910", "o": "HUGO" }, { "p": "http://purl.uniprot.org/core/encodedBy", "s": "http://purl.uniprot.org/uniprot/Q56A03", "o": "http://linkedlifedata.com/resource/#_513536413033001E" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_5135364130330018", "o": "Calsequestrin" }, { "p": "http://purl.uniprot.org/core/orfName", "s": "http://linkedlifedata.com/resource/#_513536413033001E", "o": "mCG_5476" }, { "p": "http://www.w3.org/2004/02/skos/core#prefLabel", "s": "http://linkedlifedata.com/resource/#_513536413033001E", "o": "Casq2" }, { "p": "http://purl.uniprot.org/core/encodedBy", "s": "http://purl.uniprot.org/uniprot/Q6P7Z0", "o": "http://linkedlifedata.com/resource/#_513650375A3000F" }, { "p": "http://www.w3.org/2004/02/skos/core#prefLabel", "s": "http://linkedlifedata.com/resource/#_513650375A3000F", "o": "casq2" }, { "p": "http://www.w3.org/2004/02/skos/core#altLabel", "s": "http://linkedlifedata.com/resource/#_513650375A3000F", "o": "MGC76326" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_513650375A3000A", "o": "Calsequestrin" }, { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A6899061", "o": "Metathesaurus Names" }, { "p": "http://purl.uniprot.org/core/encodedBy", "s": "http://purl.uniprot.org/uniprot/P12637", "o": "http://linkedlifedata.com/resource/#_5031323633370011" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_50313236333700E", "o": "Calsequestrin-2" }, { "p": "http://www.w3.org/2004/02/skos/core#prefLabel", "s": "http://linkedlifedata.com/resource/#_5031323633370011", "o": "CASQ2" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_50313236333700F", "o": "Calsequestrin, cardiac muscle isoform" }, { "p": "http://purl.uniprot.org/core/encodedBy", "s": "http://purl.uniprot.org/uniprot/Q5RAN9", "o": "http://linkedlifedata.com/resource/#_513552414E3900D" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_513552414E3900A", "o": "Calsequestrin-2" }, { "p": "http://www.w3.org/2004/02/skos/core#prefLabel", "s": "http://linkedlifedata.com/resource/#_513552414E3900D", "o": "CASQ2" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_513552414E3900B", "o": "Calsequestrin, cardiac muscle isoform" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A6792080", "o": "C443109" }, { "p": "http://www.w3.org/2008/05/skos-xl#prefLabel", "s": "http://linkedlifedata.com/resource/umls/id/C1432385", "o": "http://linkedlifedata.com/resource/umls/label/A6792080" }, { "p": "http://linkedlifedata.com/resource/umls/altMetaMap", "s": "http://linkedlifedata.com/resource/umls/id/C1432385", "o": "http://linkedlifedata.com/resource/umls/label/A6809413" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A6792080", "o": "CASQ2 protein, human" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A6809413", "o": "calsequestrin 2, human" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A6809413", "o": "C443109" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A8597538", "o": "C503872" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C1610406", "o": "http://linkedlifedata.com/resource/umls/label/A8597538" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A8597538", "o": "CASQ2 protein, rat" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A8603121", "o": "caisequestrin 2, rat" }, { "p": "http://linkedlifedata.com/resource/umls/prefMetaMap", "s": "http://linkedlifedata.com/resource/umls/id/C1610406", "o": "http://linkedlifedata.com/resource/umls/label/A8603121" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A8603121", "o": "C503872" }, { "p": "http://purl.uniprot.org/core/encodedBy", "s": "http://purl.uniprot.org/uniprot/O09161", "o": "http://linkedlifedata.com/resource/#_4F303931363100F" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_4F303931363100E", "o": "Calsequestrin, cardiac muscle isoform" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_4F303931363100D", "o": "Calsequestrin-2" }, { "p": "http://www.w3.org/2004/02/skos/core#prefLabel", "s": "http://linkedlifedata.com/resource/#_4F303931363100F", "o": "Casq2" }, { "p": "http://purl.uniprot.org/core/encodedBy", "s": "http://purl.uniprot.org/uniprot/O14958", "o": "http://linkedlifedata.com/resource/#_4F3134393538001B" }, { "p": "http://www.w3.org/2004/02/skos/core#prefLabel", "s": "http://linkedlifedata.com/resource/#_4F3134393538001B", "o": "CASQ2" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_4F31343935380018", "o": "Calsequestrin, cardiac muscle isoform" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_4F31343935380017", "o": "Calsequestrin-2" }, { "p": "http://purl.uniprot.org/core/encodedBy", "s": "http://purl.uniprot.org/uniprot/O18934", "o": "http://linkedlifedata.com/resource/#_4F313839333400B" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_4F313839333400A", "o": "Calsequestrin, cardiac muscle isoform" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_4F3138393334009", "o": "Calsequestrin-2" }, { "p": "http://www.w3.org/2004/02/skos/core#prefLabel", "s": "http://linkedlifedata.com/resource/#_4F313839333400B", "o": "CASQ2" }, { "p": "http://purl.uniprot.org/core/encodedBy", "s": "http://purl.uniprot.org/uniprot/P31235", "o": "http://linkedlifedata.com/resource/#_50333132333500D" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_50333132333500B", "o": "Calsequestrin-2" }, { "p": "http://www.w3.org/2004/02/skos/core#prefLabel", "s": "http://linkedlifedata.com/resource/#_50333132333500D", "o": "CASQ2" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_50333132333500C", "o": "Calsequestrin, cardiac muscle isoform" }, { "p": "http://purl.uniprot.org/core/encodedBy", "s": "http://purl.uniprot.org/uniprot/P51868", "o": "http://linkedlifedata.com/resource/#_503531383638001C" }, { "p": "http://www.w3.org/2004/02/skos/core#prefLabel", "s": "http://linkedlifedata.com/resource/#_503531383638001C", "o": "Casq2" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_5035313836380017", "o": "Calsequestrin-2" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_5035313836380018", "o": "Calsequestrin, cardiac muscle isoform" }, { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A6792080", "o": "MeSH" }, { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A6809413", "o": "MeSH" }, { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A8597538", "o": "MeSH" }, { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A8603121", "o": "MeSH" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A11276089", "o": "C514388" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A11278195", "o": "calsequestrin 2, mouse" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A11278194", "o": "casq2 protein, mouse" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C1742998", "o": "http://linkedlifedata.com/resource/umls/label/A11278195" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A11276089", "o": "cardiac calsequestrin 2, mouse" }, { "p": "http://linkedlifedata.com/resource/umls/prefMetaMap", "s": "http://linkedlifedata.com/resource/umls/id/C1742998", "o": "http://linkedlifedata.com/resource/umls/label/A11278194" }, { "p": "http://linkedlifedata.com/resource/umls/altMetaMap", "s": "http://linkedlifedata.com/resource/umls/id/C1742998", "o": "http://linkedlifedata.com/resource/umls/label/A11276089" }, { "p": "http://www.w3.org/2008/05/skos-xl#prefLabel", "s": "http://linkedlifedata.com/resource/umls/id/C1742998", "o": "http://linkedlifedata.com/resource/umls/label/A11278194" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A11278194", "o": "C514388" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A11278195", "o": "C514388" }, { "p": "http://purl.uniprot.org/core/encodedBy", "s": "http://purl.uniprot.org/uniprot/Q6PBF1", "o": "http://linkedlifedata.com/resource/#_5136504246310010" }, { "p": "http://www.w3.org/2004/02/skos/core#altLabel", "s": "http://linkedlifedata.com/resource/#_5136504246310010", "o": "casq2" }, { "p": "http://www.w3.org/2004/02/skos/core#prefLabel", "s": "http://linkedlifedata.com/resource/#_5136504246310010", "o": "casq1" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_51365042463100B", "o": "Calsequestrin" }, { "p": "http://purl.uniprot.org/core/encodedBy", "s": "http://purl.uniprot.org/uniprot/Q7ZWM0", "o": "http://linkedlifedata.com/resource/#_51375A574D300011" }, { "p": "http://www.w3.org/2004/02/skos/core#prefLabel", "s": "http://linkedlifedata.com/resource/#_51375A574D300011", "o": "casq1" }, { "p": "http://www.w3.org/2004/02/skos/core#altLabel", "s": "http://linkedlifedata.com/resource/#_51375A574D300011", "o": "casq2" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_51375A574D3000C", "o": "Calsequestrin" } ]

[ "http://www.uniprot.org/uniprot/CASQ2_CHICK", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005796", "http://www.uniprot.org/uniprot/CASQ2_PIG", "http://www.uniprot.org/uniprot/CASQ2_PONAB", "http://www.uniprot.org/uniprot/CASQ2_HUMAN", "http://www.uniprot.org/uniprot/CASQ2_CANFA", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009154", "http://www.uniprot.org/uniprot/CASQ2_RAT", "http://www.uniprot.org/uniprot/CASQ2_RABIT", "http://www.uniprot.org/uniprot/CASQ2_MOUSE" ]

[ "There are two major exceptions to the canonical GT-AG dinucleotides at donor and acceptor sites: the GG-AG splice site pairs, recognized through the typical U2 splicing machinery, and the AT-AC splice pairs recognized by the U12 splicing machinery." ]

[]

[ "About 1-2% of introns are non-canonical, with the most abundant subtype of non-canonical introns being characterized by GC and AG dinucleotides at their 5'- and 3'-termini, respectively.", "Our results indicate that the incorporation of non-canonical splice site models yields dramatic improvements in annotating genes containing GC-AG and AT-AC non-canonical introns", "If we assume that approximately the same situation is true for the whole set of annotated mammalian non-canonical splice sites, then the 99.24% of splice site pairs should be GT-AG, 0.69% GC-AG, 0.05% AT-AC and finally only 0.02% could consist of other types of non-canonical splice sites." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/21079731", "http://www.ncbi.nlm.nih.gov/pubmed/17082203", "http://www.ncbi.nlm.nih.gov/pubmed/11058137", "http://www.ncbi.nlm.nih.gov/pubmed/11125105", "http://www.ncbi.nlm.nih.gov/pubmed/20163699", "http://www.ncbi.nlm.nih.gov/pubmed/16267086", "http://www.ncbi.nlm.nih.gov/pubmed/16306388", "http://www.ncbi.nlm.nih.gov/pubmed/11574683" ]

[]

[]

[ "Isradipine antagonizes/blocks the L-type channels." ]

[ "antagonizes", "blocks" ]

[ "The L-type channel blocker, isradipine (5 microM), had no significant effect on the amplitude or kinetics of the Ca(2+) signal.", "A comparison of the sensitivity to blockade by isradipine of the L-type currents in Purkinje cells and ventricular epicardial myocytes, which only express Ca(v)1.2, suggests that the Ca(v)1.3 channels make, at most, a minor contribution to the L-type current in canine Purkinje cells.", "Action potential repolarisation in hippocampal pyramidal neurons was slowed by the N-type channel blocker omega-conotoxin GVIA, but not by the L-type channel blocker isradipine.", "Systemic administration of isradipine, a dihydropyridine blocker of L-type channels, forces dopaminergic neurons in rodents to revert to a juvenile, Ca(2+)-independent mechanism to generate autonomous activity.", "The release of glutamate was significantly inhibited by both omega-agatoxin IVA, a P/Q-type calcium channel antagonist, and isradipine, an L type calcium channel antagonist.", "What distinguishes snail and mammalian L-type channels is a difference in dihydropyridine sensitivity: 100 nM isradipine exhibits a significant block of mammalian Ca(v) 1.2 currents without effect on snail LCa(v)1 currents.", "A comparison of the sensitivity to blockade by isradipine of the L-type currents in Purkinje cells and ventricular epicardial myocytes, which only express Ca(v)1.2, suggests that the Ca(v)1.3 channels make, at most, a minor contribution to the L-type current in canine Purkinje cells.", "Action potential repolarisation in hippocampal pyramidal neurons was slowed by the N-type channel blocker omega-conotoxin GVIA, but not by the L-type channel blocker isradipine.", "During control stimulation of the presynaptic GABAergic neuron at 40 Hz for 1-2 s, DeltaF/F(0) increased rapidly to a peak value and started to decline shortly after the train ended, returning to baseline within 10-20 s. The L-type channel blocker, isradipine (5 microM), had no significant effect on the amplitude or kinetics of the Ca(2+) signal.", "The release of glutamate was significantly inhibited by both omega-agatoxin IVA, a P/Q-type calcium channel antagonist, and isradipine, an L type calcium channel antagonist.", "The L-type channel antagonist isradipine is neuroprotective in a mouse model of Parkinson's disease.", "L-type voltage-gated calcium channel blockade with isradipine as a therapeutic strategy for Alzheimer's disease.", "Effects of isradipine, an L-type calcium channel blocker on permanent and transient focal cerebral ischemia in spontaneously hypertensive rats.", "The release of glutamate was significantly inhibited by both omega-agatoxin IVA, a P/Q-type calcium channel antagonist, and isradipine, an L type calcium channel antagonist. Omega-conotoxin GVIA, an N type calcium channel antagonist and flunarizine, a nonselective T-type calcium channel antagonist were without effect.", "Action potential repolarisation in hippocampal pyramidal neurons was slowed by the N-type channel blocker omega-conotoxin GVIA, but not by the L-type channel blocker isradipine. These data showed that selective functional coupling between N-type Ca(2+) and BK channels provided rapid activation of BK channels in central neurons." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/17218348", "http://www.ncbi.nlm.nih.gov/pubmed/20816785", "http://www.ncbi.nlm.nih.gov/pubmed/11285265", "http://www.ncbi.nlm.nih.gov/pubmed/17884683", "http://www.ncbi.nlm.nih.gov/pubmed/11283860", "http://www.ncbi.nlm.nih.gov/pubmed/18996099", "http://www.ncbi.nlm.nih.gov/pubmed/17311846", "http://www.ncbi.nlm.nih.gov/pubmed/19385055", "http://www.ncbi.nlm.nih.gov/pubmed/8178970", "http://www.ncbi.nlm.nih.gov/pubmed/9398449", "http://www.ncbi.nlm.nih.gov/pubmed/21487241", "http://www.ncbi.nlm.nih.gov/pubmed/9585150", "http://www.ncbi.nlm.nih.gov/pubmed/21515375", "http://www.ncbi.nlm.nih.gov/pubmed/21925266", "http://www.ncbi.nlm.nih.gov/pubmed/7978480" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D020746", "http://www.biosemantics.org/jochem#4250298", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D017275" ]

[ "Cranberry products affect the surface properties, such as fimbriae and lipopolysaccharides, and adhesion of fimbriated and nonfimbriated E. coli." ]

[]

[ " Cranberry products affect the surface properties, such as fimbriae and lipopolysaccharides, and adhesion of fimbriated and nonfimbriated E. coli. ", " Cranberry juice has been shown to be effective in preventing adhesion of bacteria such as Escherichia coli to the bladder epithelium.", "Inhibition of adherence to an extent of about 70% with multi-drug resistant E. coli strains was observed on uroepithelial cell. The anti-adherence bioactivity of the proanthocyanidin was detected at concentrations of 10-50 µg/ml with significant bacteriuria. ", "Still with regard to antibiotic treatment in women, a recently published study investigated also the potential cranberry juice interaction with beta-lactam antibiotics supporting the hypothesis that cranberry juice in usual quantities as prophylaxis for UTI is not likely to alter the pharmacokinetics of these oral antibiotics.", "In vitro studies have shown that binding of the P fimbriae of Escherichia coli to the uroepithelial tissue can be inhibited in the presence of proanthocyanidins, the active ingredient of cranberries.", "NDM at concentrations between 0.2/mL and 1mg/mL significantly (P<.05) decreased secretion of extracellular FTF, as well as down-regulated ftf expression in a dose-dependent manner. NDM also markedly reduced the luciferase activity under the ftf promoter.", "Cranberry juice has long been recognized in folk medicine as a therapeutic agent, mainly in urinary tract infections. Its proposed mechanism of action is antiadhesion of bacteria. ", "The AFM adhesion force measurements were consistent with the results of a hemagglutination assay, confirming that oral consumption of CJC could act against adhesion of uropathogenic E. coli.", "These data suggest that daily consumption of concentrated cranberry juice can significantly prevent the recurrence of symptomatic UTIs in children." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/21688109", "http://www.ncbi.nlm.nih.gov/pubmed/19921981", "http://www.ncbi.nlm.nih.gov/pubmed/24304610", "http://www.ncbi.nlm.nih.gov/pubmed/21480803", "http://www.ncbi.nlm.nih.gov/pubmed/19636526", "http://www.ncbi.nlm.nih.gov/pubmed/19257836", "http://www.ncbi.nlm.nih.gov/pubmed/20495471", "http://www.ncbi.nlm.nih.gov/pubmed/23440506", "http://www.ncbi.nlm.nih.gov/pubmed/9110682", "http://www.ncbi.nlm.nih.gov/pubmed/19284180", "http://www.ncbi.nlm.nih.gov/pubmed/22499815" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D029799", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D014552", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D014551" ]

[ "Parkinson's disease\nCOPD\nFood hypersensitivity\nNiacin induced flushing\nHemophilia\nHeartburn\nHeadache" ]

[ "Parkinson's disease", "COPD", "Chronic obstructive pulmonary disease", "Chronic Obstructive Airways Disease", "Chronic Obstructive Lung Disease", "Food hypersensitivity", "Allergy", "Niacin induced flushing", "Hemophilia", "Heartburn", "Reflux", "GERD", "Esophageal reflux", "Headache", "Migraine", "migraine headache", "Migraine Disorder", "Migraine Headaches" ]

[ "WiiPD is an approach for the objective home based assessment of Parkinson's disease which utilizes the intuitive and sensor rich Nintendo Wii Remote. Combined with an electronic patient diary, a suite of mini-games, a metric analyzer, and a visualization engine, we propose that this system can complement existing clinical practice by providing objective metrics gathered frequently over extended periods of time.", "This research paper examines the challenges in the development and adoption of an electronic patient diary within the Pathways Home for Respiratory Illness Project", "This project supported community-based patients suffering from chronic obstructive pulmonary disease (COPD) to achieve increased levels of self-management and self-efficacy using electronic-monitoring techniques and mentoring by community health nurses.", "Instead of measuring physiological parameters, a Smartphone based Personal Allergy Assistant (PAA) allows patients to keep an electronic patient diary by scanning the barcode of the consumed food products.", "Telemedicine assisted diet and diagnosis management in food hypersensitivity", "The Flushing ASsessment Tool (FAST) was developed to assess flushing symptoms and their impact on patients receiving niacin therapy.", " This was a prospective, randomized, double-blind, placebo-controlled, parallel-group 8-week study conducted to evaluate the psychometric characteristics of the FAST. The instrument is administered daily using an electronic patient diary.", "Haemoassist--a hand-held electronic patient diary for haemophilia home care.", "A comparison of self-documentation in diabetics: electronic versus paper diaries.", "Subjects with self-perceived heartburn without known gastrointestinal disease or interfering treatments were selected with questionnaires. The study was performed unsupervised, whenever heartburn required medication. An electronic patient diary gave instructions when to take study medication", "Self-medication of a single headache episode with ketoprofen, ibuprofen or placebo, home-monitored with an electronic patient diary." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/20841643", "http://www.ncbi.nlm.nih.gov/pubmed/19301936", "http://www.ncbi.nlm.nih.gov/pubmed/22949085", "http://www.ncbi.nlm.nih.gov/pubmed/10594395", "http://www.ncbi.nlm.nih.gov/pubmed/19226411", "http://www.ncbi.nlm.nih.gov/pubmed/14728392", "http://www.ncbi.nlm.nih.gov/pubmed/19999626", "http://www.ncbi.nlm.nih.gov/pubmed/8904620" ]

[]

[]

[ "The disease focus for the irreversible epoxyketone proteasome inhibitor ixazomib is multiple myeloma." ]

[ "Multiple myeloma" ]

[ "Next generation proteasome inhibitors include carfilzomib and oprozomib which are irreversible epoxyketone proteasome inhibitors; and ixazomib and delanzomib which are reversible boronic acid proteasome inhibitors. Two proteasome inhibitors, bortezomib and carfilzomib are FDA approved drugs and ixazomib and oprozomib are in late stage clinical trials. ", "The disease focus for all the proteasome inhibitors is multiple myeloma.", "In addition, novel drug classes have shown promising activity in RR MM, including the orally-administered proteasome inhibitors ixazomib and oprozomib; monoclonal antibodies such as the anti-CS1 monoclonal antibody elotuzumab and anti-CD38 monoclonal antibody daratumumab; and histone deacetylase inhibitors such as panobinostat and rocilinostat.", "These findings have informed the subsequent clinical development of ixazomib in multiple myeloma.", "Phase 1 study of twice-weekly ixazomib, an oral proteasome inhibitor, in relapsed/refractory multiple myeloma patients.", "An evidence-based review of ixazomib citrate and its potential in the treatment of newly diagnosed multiple myeloma.", "Phase 1 study of weekly dosing with the investigational oral proteasome inhibitor ixazomib in relapsed/refractory multiple myeloma.", "(18)F-FDG-PET/CT imaging in an IL-6- and MYC-driven mouse model of human multiple myeloma affords objective evaluation of plasma cell tumor progression and therapeutic response to the proteasome inhibitor ixazomib.", "Sixty patients with relapsed and/or refractory multiple myeloma were enrolled on this phase 1 trial to evaluate safety and tolerability and determine the maximum tolerated dose (MTD) of single-agent, oral ixazomib given weekly for 3 of 4 weeks.", "Sixty patients with relapsed and/or refractory multiple myeloma were enrolled on this phase 1 trial to evaluate safety and tolerability and determine the maximum tolerated dose (MTD) of single-agent, oral ixazomib given weekly for 3 of 4 weeks", "Among second-generation proteasome inhibitors, ixazomib (MLN9708) is the first oral compound to be evaluated for the treatment of MM", "Sixty patients with relapsed and/or refractory multiple myeloma were enrolled on this phase 1 trial to evaluate safety and tolerability and determine the maximum tolerated dose (MTD) of single-agent, oral ixazomib given weekly for 3 of 4 weeks. ", "Ixazomib is the first investigational oral proteasome inhibitor to be studied clinically. In this phase 1 trial, 60 patients with relapsed/refractory multiple myeloma (median of 4 prior lines of therapy; bortezomib, lenalidomide, thalidomide, and carfilzomib/marizomib in 88%, 88%, 62%, and 5%, respectively) received single-agent ixazomib 0.24 to 2.23 mg/m(2) (days 1, 4, 8, 11; 21-day cycles). ", "Safety and tolerability of ixazomib, an oral proteasome inhibitor, in combination with lenalidomide and dexamethasone in patients with previously untreated multiple myeloma: an open-label phase 1/2 study.", "In a phase 1/2 trial we aimed to assess the safety, tolerability, and activity of ixazomib in combination with lenalidomide and dexamethasone in newly diagnosed multiple myeloma.METHODS: We enrolled patients newly diagnosed with multiple myeloma aged 18 years or older with measurable disease, Eastern Cooperative Oncology Group performance status 0-2, and no grade 2 or higher peripheral neuropathy, and treated them with oral ixazomib (days 1, 8, 15) plus lenalidomide 25 mg (days 1-21) and dexamethasone 40 mg (days 1, 8, 15, 22) for up to 12 28-day cycles, followed by maintenance therapy with ixazomib alone. ", "Among second-generation proteasome inhibitors, ixazomib (MLN9708) is the first oral compound to be evaluated for the treatment of MM. Ixazomib has shown improved pharmacokinetic and pharmacodynamic parameters compared with bortezomib, in addition to similar efficacy in the control of myeloma growth and prevention of bone loss.", "Among 55 response-evaluable patients, 15% achieved partial response or better (76% stable disease or better). These findings have informed the subsequent clinical development of ixazomib in multiple myeloma.", "Ixazomib is an investigational, orally bioavailable 20S proteasome inhibitor. Sixty patients with relapsed and/or refractory multiple myeloma were enrolled on this phase 1 trial to evaluate safety and tolerability and determine the maximum tolerated dose (MTD) of single-agent, oral ixazomib given weekly for 3 of 4 weeks." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/24920586", "http://www.ncbi.nlm.nih.gov/pubmed/24292417", "http://www.ncbi.nlm.nih.gov/pubmed/24904120", "http://www.ncbi.nlm.nih.gov/pubmed/24471924", "http://www.ncbi.nlm.nih.gov/pubmed/25268212", "http://www.ncbi.nlm.nih.gov/pubmed/24486586", "http://www.ncbi.nlm.nih.gov/pubmed/24712303", "http://www.ncbi.nlm.nih.gov/pubmed/24578203", "http://www.ncbi.nlm.nih.gov/pubmed/25456369", "http://www.ncbi.nlm.nih.gov/pubmed/25302026", "http://www.ncbi.nlm.nih.gov/pubmed/25935605" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009101" ]

[ "Autophagy (Autophagy-related protein 8 or Atg8p or APG8 or AUT7 or CVT5) is a yeast protein involved in cytoplasm to vacuole transport (Cvt) vesicles and autophagosomes formation. In yeast it is represented by a single gene, the ATG8 family in humans contains 6 members (microtubule-associated protein-1 light chain 3A (MAP1LC3A), MAP1LC3B, MAP1LC3C, GABA(A) receptor-associated protein (GABARAP), GABARAPL1, and GABARAPL2/GATE-16)." ]

[ "MAP1LC3A", "microtubule-associated protein-1 light chain 3A", "LC3A", "MAP1LC3B", "microtubule-associated protein-1 light chain 3B", "LC3B", "MAP1LC3C", "microtubule-associated protein-1 light chain 3C", "LC3C", "GABARAP", "GABA(A) receptor-associated protein", "Gamma-aminobutyric acid receptor-associated protein", "MM46", "GABARAPL1", "Gamma-aminobutyric acid receptor-associated protein-like 1", "Early estrogen-regulated protein", "GABA(A) receptor-associated protein-like 1", "Glandular epithelial cell protein 1", "GEC-1", "GABARAPL2", "Gamma-aminobutyric acid receptor-associated protein-like 2", "GABA(A) receptor-associated protein-like 2", "Ganglioside expression factor 2", "GEF-2", "General protein transport factor p16", "Golgi-associated ATPase enhancer of 16 kDa", "GATE-16", "MAP1 light chain 3-related protein" ]

[ "Strikingly, in addition to ULK1 and ULK2, ATG13 and FIP200 interacted with human ATG8 proteins, all with strong preference for the GABARAP subfamily.", "GABARAPL1 belongs to the small family of GABARAP proteins (including GABARAP, GABARAPL1 and GABARAPL2/GATE-16), one of the two subfamilies of the yeast Atg8 orthologue.", "Identification of the Atg8 family interacting motif (AIM) in Stbd1 required for interaction with GABARAPL1", "Stbd1 has been reported to interact with a known autophagy protein, GABARAPL1, a member of the Atg8 family.", "Atg8 is a yeast protein involved in the autophagic process and in particular in the elongation of autophagosomes. In mammals, several orthologs have been identified and are classed into two subfamilies: the LC3 subfamily and the GABARAP subfamily, referred to simply as the LC3 or GABARAP families. GABARAPL1 (GABARAP-like protein 1), one of the proteins belonging to the GABARAP (GABA(A) receptor-associated protein) family", "The proteins that make up the GABARAP family demonstrate conservation of their amino acid sequences and protein structures. In humans, GABARAPL1 shares 86% identity with GABARAP and 61% with GABARAPL2 (GATE-16).", "The selectivity is mediated by autophagy receptors, such as p62 and NBR1, which can bind to autophagic effector proteins (Atg8 in yeast, MAP1LC3 protein family in mammals) anchored in the membrane of autophagosomes.", "ATG3 is the E2-like enzyme necessary for ATG8/LC3 lipidation during autophagy.", "Recently, autophagy receptors, like p62/SQSTM1 and NBR1, which physically link autophagic cargo to ATG8/MAP1-LC3/GABARAP family members located on the forming autophagic membranes, have been identified.", "At least eight different Atg8 orthologs belonging to two subfamilies (LC3 and GATE-16/GABARAP) occur in mammalian cells, but their individual roles and modes of action are largely unknown.", "truncated DeltaN63 Atg4D displays increased activity against the Atg8 paralogue, gamma-aminobutyric acid receptor-associated protein-like 1 (GABARAP-L1)", "Structure of GATE-16, membrane transport modulator and mammalian ortholog of autophagocytosis factor Aut7p.", "The yeast ortholog of GATE-16 is the autophagocytosis factor Aut7p. GATE-16 is also closely related to the GABA receptor-associated protein (GABARAP),", "Three human Atg8 (hAtg8) homologs, LC3, GABARAP, and GATE-16, have been characterized as modifiers in reactions mediated by hAtg7 (an E1-like enzyme) and hAtg3 (an E2-like enzyme) as in yeast Atg8 lipidation, but their final targets have not been identified." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/21620860", "http://www.ncbi.nlm.nih.gov/pubmed/21893048", "http://www.ncbi.nlm.nih.gov/pubmed/23043107", "http://www.ncbi.nlm.nih.gov/pubmed/20418806", "http://www.ncbi.nlm.nih.gov/pubmed/21862879", "http://www.ncbi.nlm.nih.gov/pubmed/20723759", "http://www.ncbi.nlm.nih.gov/pubmed/22948227", "http://www.ncbi.nlm.nih.gov/pubmed/10856287", "http://www.ncbi.nlm.nih.gov/pubmed/16303767", "http://www.ncbi.nlm.nih.gov/pubmed/22120110", "http://www.ncbi.nlm.nih.gov/pubmed/20562859", "http://www.ncbi.nlm.nih.gov/pubmed/22302004", "http://www.ncbi.nlm.nih.gov/pubmed/19549685", "http://www.ncbi.nlm.nih.gov/pubmed/20574168", "http://www.ncbi.nlm.nih.gov/pubmed/23022382" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D006801", "http://www.uniprot.org/uniprot/ATG8_MAGO7" ]

[ "The Zika virus belongs to the family Flaviviridae." ]

[ "Flaviviridae" ]

[ "Zika virus (ZIKV; genus Flavivirus, family Flaviviridae) " ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/25310102" ]

[ { "p": "http://purl.uniprot.org/core/reviewed", "s": "http://purl.uniprot.org/taxonomy/64320", "o": "false" }, { "p": "http://purl.uniprot.org/core/scientificName", "s": "http://purl.uniprot.org/taxonomy/64320", "o": "Zika virus" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A0820708", "o": "64320" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A0820708", "o": "Zika virus" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A14224049", "o": "Zika virus (organism)" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C0318793", "o": "http://linkedlifedata.com/resource/umls/label/A0820708" }, { "p": "http://www.w3.org/2008/05/skos-xl#prefLabel", "s": "http://linkedlifedata.com/resource/umls/id/C0318793", "o": "http://linkedlifedata.com/resource/umls/label/A14224049" }, { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A0820708", "o": "NCBI Taxonomy" }, { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A14224049", "o": "Metathesaurus Names" } ]

[ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005190", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D014780", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D014777", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009679" ]

[ "Yes, Ashbya gossypii has a budding yeast-like genome but grows exclusively as multinucleated hyphae." ]

[ "yes" ]

[ "multinucleated Ashbya gossypii cells.", "multinucleated Ashbya gossypii fungal cells", "Nuclei in the filamentous, multinucleated fungus Ashbya gossypii divide asynchronously. ", "multinucleated Ashbya gossypii cells", "We analyzed a unique asynchronous nuclear division cycle in a multinucleated filamentous fungus, Ashbya gossypii.", " multinucleated hyphae in Ashbya gossypii.", "We have followed the migration of GFP-labelled nuclei in multinucleate hyphae of Ashbya gossypii", "multinucleate fungus Ashbya gossypii", "Ashbya gossypii grows as multinucleated and constantly elongating hyphae", "multinucleated hyphae of Ashbya gossypii.", "We report the mechanistic basis guiding the migration pattern of multiple nuclei in hyphae of Ashbya gossypii. ", "multinucleate fungal cells", "multinucleate Ashbya gossypii cells relies on a minimal network of genes", "Clustering of nuclei in multinucleated hyphae is prevented by dynein-driven bidirectional nuclear movements and microtubule growth control in Ashbya gossypii.", "In the multinucleate fungus Ashbya gossypii, cytoplasmic microtubules (cMTs) emerge from the spindle pole body outer plaque (OP) in perpendicular and tangential directions.", "multinucleated hyphae of Ashbya gossypii.", "multiple nuclei in Ashbya gossypii hyphae", "Ashbya gossypii has a budding yeast-like genome but grows exclusively as multinucleated hyphae." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/24094857", "http://www.ncbi.nlm.nih.gov/pubmed/20053682", "http://www.ncbi.nlm.nih.gov/pubmed/16449188", "http://www.ncbi.nlm.nih.gov/pubmed/16023404", "http://www.ncbi.nlm.nih.gov/pubmed/17158735", "http://www.ncbi.nlm.nih.gov/pubmed/23015595", "http://www.ncbi.nlm.nih.gov/pubmed/21737675", "http://www.ncbi.nlm.nih.gov/pubmed/21642510", "http://www.ncbi.nlm.nih.gov/pubmed/16899511", "http://www.ncbi.nlm.nih.gov/pubmed/22267774", "http://www.ncbi.nlm.nih.gov/pubmed/20844079", "http://www.ncbi.nlm.nih.gov/pubmed/11181180", "http://www.ncbi.nlm.nih.gov/pubmed/17122387", "http://www.ncbi.nlm.nih.gov/pubmed/19910487", "http://www.ncbi.nlm.nih.gov/pubmed/23771903" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D002467", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D002529" ]

[ "Triplex is an R/Bioconductor package for identification and visualization of potential intramolecular triplex patterns in DNA sequences. The package provides functions that can be used to search Bioconductor genomes and other DNA sequence data for occurrence of nucleotide patterns capable of forming intramolecular triplexes (H-DNA). Functions producing 2D and 3D diagrams of the identified triplexes allow instant visualization of the search results. Leveraging the power of Biostrings and GRanges classes, the results get fully integrated into the existing Bioconductor framework, allowing their passage to other Genome visualization and annotation packages, such as GenomeGraphs, rtracklayer or Gviz." ]

[]

[ "Triplex: an R/Bioconductor package for identification and visualization of potential intramolecular triplex patterns in DNA sequences.", "The new package provides functions that can be used to search Bioconductor genomes and other DNA sequence data for occurrence of nucleotide patterns capable of forming intramolecular triplexes (H-DNA). Functions producing 2D and 3D diagrams of the identified triplexes allow instant visualization of the search results. Leveraging the power of Biostrings and GRanges classes, the results get fully integrated into the existing Bioconductor framework, allowing their passage to other Genome visualization and annotation packages, such as GenomeGraphs, rtracklayer or Gviz.", "RESULTS: We combined a previously published implementation of a triplex DNA search algorithm with visualization to create a versatile R/Bioconductor package 'triplex'. The new package provides functions that can be used to search Bioconductor genomes and other DNA sequence data for occurrence of nucleotide patterns capable of forming intramolecular triplexes (H-DNA). Functions producing 2D and 3D diagrams of the identified triplexes allow instant visualization of the search results. " ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/23709494" ]

[]

[]

[ "Activating point mutations most frequently in codon 12" ]

[ "Point mutations" ]

[ "activating mutations in KRAS are identified in most pancreatic cancers", "Mutations at codon 12 of the K-ras gene are present in 65%-100% of carcinomas of human exocrine pancreas and could be used as a potential tumor marker at the tissue level.", "Activating point mutations in the K-Ras oncogene are among the most common genetic alterations in pancreatic cancer, occurring early in the progression of the disease.", "Activating K-ras mutations are found in approximately 90% of pancreatic carcinomas and may contribute to the poor prognosis of these tumors.", "Five of the seven duct lesions harbored activating point mutations in codon 12 of K-ras; a G to A transition was found in four and a G to C transversion in one.", "Ki-RAS mutations in 38% of the overall series", "KRAS exon 2 mutations were detected in a total of 62 patients with the two methods combined, comprising 11 different mutant alleles.", "gain-of-function mutations in ras genes were the first specific genetic alterations identified in human cancer" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/19509115", "http://www.ncbi.nlm.nih.gov/pubmed/12697967", "http://www.ncbi.nlm.nih.gov/pubmed/19783717", "http://www.ncbi.nlm.nih.gov/pubmed/8613066", "http://www.ncbi.nlm.nih.gov/pubmed/21779504", "http://www.ncbi.nlm.nih.gov/pubmed/8178941", "http://www.ncbi.nlm.nih.gov/pubmed/16757361", "http://www.ncbi.nlm.nih.gov/pubmed/16166322", "http://www.ncbi.nlm.nih.gov/pubmed/19826477", "http://www.ncbi.nlm.nih.gov/pubmed/21626008", "http://www.ncbi.nlm.nih.gov/pubmed/21886451" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011905", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0032856", "http://www.disease-ontology.org/api/metadata/DOID:305" ]

[ "Myocardial remodeling after an ischemic insult involves extracellular matrix proteins with increased fibrosis\nInitial experimental data indicate that miRNA 30 decreases CTGF a key molecule in the process of fibrosis, by directly downregulating the production of CTGF" ]

[ "yes" ]

[ "The myocardium of the failing heart undergoes a number of structural alterations, most notably hypertrophy of cardiac myocytes and an increase in extracellular matrix proteins, often seen as primary fibrosi", "Connective tissue growth factor (CTGF) is a key molecule in the process of fibrosis and therefore seems an attractive therapeutic target", "CTGF is importantly regulated by 2 major cardiac microRNAs (miRNAs), miR-133 and miR-30.", "the expression of both miRNAs was inversely related to the amount of CTGF in 2 rodent models of heart disease and in human pathological left ventricular hypertrophy. Second, in cultured cardiomyocytes and fibroblasts, knockdown of these miRNAs increased CTGF levels. Third, overexpression of miR-133 or miR-30c decreased CTGF levels, which was accompanied by decreased production of collagens.", "miR-30 importantly limit the production of CTGF", "miR-30 directly downregulate CTGF, a key profibrotic protein, and thereby establish an important role for these miRNAs in the control of structural changes in the extracellular matrix of the myocardium." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/22352753", "http://www.ncbi.nlm.nih.gov/pubmed/21434842", "http://www.ncbi.nlm.nih.gov/pubmed/22038740", "http://www.ncbi.nlm.nih.gov/pubmed/19096030" ]

[]

[ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0010586", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D020257", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D035683" ]

[ "'Use of a Multidrug Pill In Reducing cardiovascular Events' (UMPIRE) trial, European Clinical Trials database, as EudraCT: 2009-016278-34 and the Clinical Trials Registry, India as CTRI/2010/091/000250.\n'IMProving Adherence using Combination Therapy (IMPACT)', Australian New Zealand Clinical Trial Registry (ACTRN12606000067572).\n'Kanyini Guidelines Adherence with the Polypill (Kanyini-GAP)'\nPhase II study of the Polycap, double-blind, randomised trial, registered with ClinicalTrials.gov, number NCT00443794\nSecond Indian Polycap Study, TIPS-2\nCluster Randomized Usual Care vs Caduet Investigation Assessing Long-term-risk (CRUCIAL trial)\nGEMINI trial, 14-week, open-label trial conducted in 1220 patients from the USA\nGEMINI-Australia, Asia, Latin America, Africa/Middle East (AALA) study \nJEWEL study program, with JEWEL 1 conducted among 1138 patients from the UK and Canada and JEWEL 2 conducted in 1107 patients from Europe\nCAPABLE54, the Clinical Utility of Caduet in Simultaneously Achieving Blood Pressure and Lipid End Points , in the USA\nCUSP (The Caduet® in an Untreated Subject Population trial)\nTOGETHER trial\nA randomised controlled trial in seven countries – Australia, Brazil, India, Netherlands , New Zealand , United Kingdom and United States. Australian New Zealand Clinical Trials Registry (ACTRN 12607000099426)", "A number of clinical trials evaluating polypill, mainly in cardiovascular patients, have been performed and include the Use of a Multidrug Pill In Reducing cardiovascular Events (UMPIRE) trial, Cluster Randomized Usual Care vs Caduet Investigation Assessing Long-term-risk (CRUCIAL trial), Atorvastatin and Amlodipine in Patients with Elevated Lipids and Hypertension (AVALON) trial, Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT), GEMINI trial, GEMINI-Australia, Asia, Latin America, Africa/Middle East (GEMINI-AALA) study, JEWEL 1 trial, JEWEL 2 trial, Clinical Utility of Caduet in Simultaneously Achieving Blood Pressure and Lipid End Points (CAPABLE54), The Caduet® in an Untreated Subject Population trial (CUSP), TOGETHER trial, TIPS trial, TIPS-2 trial and IMProving Adherence using Combination Therapy (IMPACT)." ]

[ "Use of a Multidrug Pill In Reducing cardiovascular Events' (UMPIRE) trial, European Clinical Trials database\\, as EudraCT: 2009-016278-34 and the Clinical Trials Registry\\, India as CTRI/2010/091/000250.", "UMPIRE", "IMProving Adherence using Combination Therapy (IMPACT)', Australian New Zealand Clinical Trial Registry (ACTRN12606000067572)", "IMPACT", "Kanyini Guidelines Adherence with the Polypill (Kanyini-GAP)", "Phase II study of the Polycap, double-blind\\, randomised trial\\, registered with ClinicalTrials.gov\\, number NCT00443794", "ndian Polycap Study, TIPS", "TIPS", "Cluster Randomized Usual Care vs Caduet Investigation Assessing Long-term-risk (CRUCIAL trial)", "CRUCIAL", "GEMINI trial, 14-week\\, open-label trial conducted in 1220 patients from the USA", "GEMINI", "GEMINI-Australia, Asia\\, Latin America\\, Africa/Middle East (AALA) study", "GEMINI-AALA", "JEWEL 1 conducted among 1138 patients from the UK and Canada", "JEWEL 1", "JEWEL 2 conducted in 1107 patients from Europe", "JEWEL 2", "CAPABLE54, the Clinical Utility of Caduet in Simultaneously Achieving Blood Pressure and Lipid End Points\\, in the USA", "CAPABLE54", "CUSP (The Caduet® in an Untreated Subject Population trial)", "CUSP", "TOGETHER trial", "TOGETHER", "A randomised controlled trial in seven countries – Australia, Brazil\\, India\\, Netherlands\\, New Zealand\\, United Kingdom and United States\\, Australian New Zealand Clinical Trials Registry (ACTRN 12607000099426)", "Second Indian Polycap Study, TIPS-2", "TIPS-2", " Atorvastatin and Amlodipine in Patients with Elevated Lipids and Hypertension (AVALON) trial", "AVALON", "Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT)", "ASCOT" ]

[ "The 'Use of a Multidrug Pill In Reducing cardiovascular Events' (UMPIRE) trial assesses whether a polypill strategy (by combining aspirin, a statin and two blood pressure lowering agents) would improve adherence to guideline-indicated therapies and would lower both blood pressure and cholesterol, in people with established cardiovascular disease. UMPIRE, running in India and three European countries (England, Ireland and the Netherlands), is an open, randomised, controlled trial designed to include 1000 participants in India and 1000 in Europe, with a followup of 12-24 months.", "UMPIRE is registered with the European Clinical Trials database, as EudraCT: 2009-016278-34 and the Clinical Trials Registry, India as CTRI/2010/091/000250. The trial was part of the 'Single Pill Against Cardiovascular Events (SPACE)' collaboration, which encompasses the 'IMProving Adherence using Combination Therapy (IMPACT)' and 'Kanyini Guidelines Adherence with the Polypill (Kanyini-GAP)' trials.", "IMProving Adherence using Combination Therapy (IMPACT) is an open-label randomised controlled trial comparing a once-daily polypill containing four preventive medications with usual care", "The trial is registered with the Australian New Zealand Clinical Trial Registry (ACTRN12606000067572).", "Effects of a polypill (Polycap) on risk factors in middle-aged individuals without cardiovascular disease (TIPS): a phase II, double-blind, randomised trial.", "This study is registered with ClinicalTrials.gov, number NCT00443794" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/15670547", "http://www.ncbi.nlm.nih.gov/pubmed/21682553", "http://www.ncbi.nlm.nih.gov/pubmed/22080542", "http://www.ncbi.nlm.nih.gov/pubmed/20334446", "http://www.ncbi.nlm.nih.gov/pubmed/16479100", "http://www.ncbi.nlm.nih.gov/pubmed/19339045", "http://www.ncbi.nlm.nih.gov/pubmed/22787067", "http://www.ncbi.nlm.nih.gov/pubmed/22162939", "http://www.ncbi.nlm.nih.gov/pubmed/15830173", "http://www.ncbi.nlm.nih.gov/pubmed/21777702", "http://www.ncbi.nlm.nih.gov/pubmed/20687931", "http://www.ncbi.nlm.nih.gov/pubmed/21647425", "http://www.ncbi.nlm.nih.gov/pubmed/23038750", "http://www.ncbi.nlm.nih.gov/pubmed/18227490", "http://www.ncbi.nlm.nih.gov/pubmed/21205325" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D002986" ]

[ "An unusual feature of the Diptera is that homologous chromosomes are intimately synapsed in somatic cells. At a number of loci in Drosophila, this pairing can significantly influence gene expression. Such influences were first detected within the bithorax complex (BX-C) by E.B. Lewis, who coined the term transvection to describe them. Most cases of transvection involve the action of enhancers in trans. At several loci deletion of the promoter greatly increases this action in trans, suggesting that enhancers are normally tethered in cis by the promoter region. Transvection can also occur by the action of silencers in trans or by the spreading of position effect variegation from rearrangements having heterochromatic breakpoints to paired unrearranged chromosomes. Although not demonstrated, other cases of transvection may involve the production of joint RNAs by trans-splicing. Several cases of transvection require Zeste, a DNA-binding protein that is thought to facilitate homolog interactions by self-aggregation. Genes showing transvection can differ greatly in their response to pairing disruption. In several cases, transvection appears to require intimate synapsis of homologs. However, in at least one case (transvection of the iab-5,6,7 region of the BX-C), transvection is independent of synapsis within and surrounding the interacting gene. The latter example suggests that transvection could well occur in organisms that lack somatic pairing. In support of this, transvection-like phenomena have been described in a number of different organisms, including plants, fungi, and mammals.", "Pairing-dependent interallelic complementation was first described for the Ultrabithorax gene of the bithorax-complex in Drosophila by Lewis and cited as an example of a new phenomenon that Lewis called the trans-vection effect. Several different kinds of pairing-dependent gene expression have been observed in Drosophila, and it is now clear that a variety of different molecular mechanisms probably underlie the changes in gene expression that are observed after disrupting chromosome pairing. Transvection in the bithorax-complex appears to result from the ability of cis-regulatory elements to regulate transcription of the promoter on the homologous chromosome. The same phenomenon appears to be responsible for pairing-dependent interallelic complementation at numerous other genes in Drosophila. Some transvection effects are dependent on the presence of wild-type or specific mutant forms of the protein encoded by the zeste trans-regulatory gene, but other transvection effects are zeste-independent. The ease with which chromosome aberrations can disrupt transvection also varies widely among different genes " ]

[]

[ "An unusual feature of the Diptera is that homologous chromosomes are intimately synapsed in somatic cells. At a number of loci in Drosophila, this pairing can significantly influence gene expression. Such influences were first detected within the bithorax complex (BX-C) by E.B. Lewis, who coined the term transvection to describe them. Most cases of transvection involve the action of enhancers in trans. At several loci deletion of the promoter greatly increases this action in trans, suggesting that enhancers are normally tethered in cis by the promoter region. Transvection can also occur by the action of silencers in trans or by the spreading of position effect variegation from rearrangements having heterochromatic breakpoints to paired unrearranged chromosomes. Although not demonstrated, other cases of transvection may involve the production of joint RNAs by trans-splicing. Several cases of transvection require Zeste, a DNA-binding protein that is thought to facilitate homolog interactions by self-aggregation. Genes showing transvection can differ greatly in their response to pairing disruption. In several cases, transvection appears to require intimate synapsis of homologs. However, in at least one case (transvection of the iab-5,6,7 region of the BX-C), transvection is independent of synapsis within and surrounding the interacting gene. The latter example suggests that transvection could well occur in organisms that lack somatic pairing. In support of this, transvection-like phenomena have been described in a number of different organisms, including plants, fungi, and mammals", "Pairing-dependent interallelic complementation was first described for the Ultrabithorax gene of the bithorax-complex in Drosophila by Lewis and cited as an example of a new phenomenon that Lewis called the \"trans-vection effect.\" Several different kinds of pairing-dependent gene expression have been observed in Drosophila, and it is now clear that a variety of different molecular mechanisms probably underlie the changes in gene expression that are observed after disrupting chromosome pairing. Transvection in the bithorax-complex appears to result from the ability of cis-regulatory elements to regulate transcription of the promoter on the homologous chromosome. The same phenomenon appears to be responsible for pairing-dependent interallelic complementation at numerous other genes in Drosophila. Some transvection effects are dependent on the presence of wild-type or specific mutant forms of the protein encoded by the zeste trans-regulatory gene, but other transvection effects are zeste-independent. The ease with which chromosome aberrations can disrupt transvection also varies widely among different genes", "The presence of homologous nucleic acid sequences can exert profound effects on chromosomal and gene function in a wide range of organisms. These homology effects reveal remarkable forms of regulation as well as suggest possible avenues for the development of new technologies", "Enhancers have been defined operationally as cis-regulatory sequences that can stimulate transcription of RNA polymerase-II-transcribed genes over large distances and even when located downstream of the gene. Recently, it has become evident that enhancers can also stimulate transcription in trans if they are brought into close proximity to the promoter/gene. These reports provide clues to the mechanism of remote enhancer action. In addition, the findings, together with genetic studies in Drosophila, strongly suggest that enhancer action in trans could underlie phenomena such as 'transvection', where one chromosome affects gene expression in the paired homolog", "Numerous genes contain regulatory elements located many tens of kilobases away from the promoter they control. Specific mechanisms must be required to ensure that such distant elements can find and interact with their proper targets but not with extraneous genes. This review explores the connections between transvection phenomena, the activation of domains of homeotic gene expression, position effect variegation and silencers. These various examples of long-distance effects suggest that, in all cases, related forms of chromatin packaging may be involved", "The zeste locus of Drosophila melanogaster encodes a DNA-binding protein that can influence transcription. A number of sites recognized by this protein fall within genes associated with transvection, a phenomenon suggesting a form of gene regulation that is responsive to the proximity of a gene to its homologous allele on another chromosome", "Special attention is paid to the transvection effect (synapsis-dependent interaction between white and zeste genes), cis-acting regulatory elements and the behaviour of the white genes introduced into the genome by P element-mediated DNA transformation" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/12429702", "http://www.ncbi.nlm.nih.gov/pubmed/2238088", "http://www.ncbi.nlm.nih.gov/pubmed/10322135", "http://www.ncbi.nlm.nih.gov/pubmed/9348657", "http://www.ncbi.nlm.nih.gov/pubmed/11931232", "http://www.ncbi.nlm.nih.gov/pubmed/11504843", "http://www.ncbi.nlm.nih.gov/pubmed/3135240", "http://www.ncbi.nlm.nih.gov/pubmed/1979484", "http://www.ncbi.nlm.nih.gov/pubmed/2505416" ]

[]

[]

[ "Probiotics are live, microbial food supplements that benefit the host animal by improving intestinal microbial balance. Across all 11 probiotic species and eight different gastrointestinal diseases - Irritable Bowel Syndrome (IBS), Helicobacter pylori infection (HPP), Necrotizing Enterocolitis (NEC), Pouchitis (Pouch), Antibiotic Associated diarrhea (AAD), Clostridium difficile Disease (CDD), Infectious diarrhea (ID), and Travellers diarrhea (TD) - probiotics have been shown to have effect on prevention and treatment of gastrointestinal disease through enhancing the immune response, protection against abnormal invasive bacteria. Probiotics have a role in all age groups, incl. infants." ]

[]

[ "The overall response rate was 80.5%, of which 69.5% of respondents said they recommended or prescribed probiotic food supplements to their patients, including 53.4% of surgeons and 80.8% of gastroenterologists (P = 0.00013). The most popular probiotic supplements among surgeons were probiotic-containing yoghurt and drinks (79.5% and 71.8%, respectively), whereas VSL#3 was more popular with gastroenterologists (83.3%). The most popular indications were irritable bowel syndrome (70.7% of prescribers) and pouchitis (67.5% of prescribers). Many respondents prescribed long-term probiotics.", "Current evidence indicates that probiotic effects are strain-specific, they do not act through the same mechanisms, and nor are all probiotics indicated for the same health conditions. However, they do share several common features in that they exert anti-inflammatory effects, they employ different strategies to antagonize competing microorganisms, and they induce cytoprotective changes in the host either through enhancement of barrier function, or through the upregulation of cytoprotective host proteins.", "Most surveyed physicians recommended probiotics for irritable bowel syndrome, antibiotic, and Clostridium difficile-associated diarrhea because they believed that the literature supports their usage for these conditions.", "This study suggests most gastrointestinal disease specialists recognize a role for and have used probiotics as part of their therapeutic armamentarium", "probiotics for these patients with small bowel bacterial overgrowth, inflammatory bowel disease, and radiation enteritis.", "These results provide some evidence that viable Bifidobacterium lactis strain Bb 12, added to an acidified infant formula, has some protective effect against acute diarrhea in healthy children.", "Probiotics are live, microbial food supplements that benefit the host animal by improving intestinal microbial balance. Their major role in preventing and treating gastrointestinal disease appears to be from their effect on the immune process, protection against abnormal invasive bacteria, and in the production of short-chain fatty acids from starch and non-starch polysaccharides." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/22529959", "http://www.ncbi.nlm.nih.gov/pubmed/15076628", "http://www.ncbi.nlm.nih.gov/pubmed/12846937", "http://www.ncbi.nlm.nih.gov/pubmed/16215086", "http://www.ncbi.nlm.nih.gov/pubmed/20890386", "http://www.ncbi.nlm.nih.gov/pubmed/21426607", "http://www.ncbi.nlm.nih.gov/pubmed/22118700", "http://www.ncbi.nlm.nih.gov/pubmed/20216432", "http://www.ncbi.nlm.nih.gov/pubmed/19930635" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005767", "http://www.disease-ontology.org/api/metadata/DOID:77", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D019936" ]

[ "The diagnosis and surgical treatment of patients with Marfan syndrome remain controversial. Pathohistological alterations of the aorta in patients with Marfan syndrome consisted in pronounced restructuring of the wall with deep irreversible alternative changes. The risk of aortic dissection, which is the most serious manifestation of the Marfan syndrome, increases as the aorta enlarges. Surgical replacement of the aortic root with a composite graft does not end the disease process.", "Marfan syndrome is a multisystemic connective tissue disorder caused mainly by mutations in the fibrillin-1 gene. The entire cardiovascular system is affected in patients with Marfan syndrome. Aortic root dilatation, which may involve the proximal and distal aorta, mitral valve prolapse, and mitral regurgitation, aortic valve regurgitation or - the most feared and life-threatening symptom - aortic root dissection are the most common manifestations.", "The diagnosis and surgical treatment of patients with Marfan syndrome remain controversial. It is of utmost importance to identify patients at risk for acute aortic events to establish the correct surgical timing and the appropriate surgical treatment" ]

[ "aortic root dissection" ]

[ "The diagnosis and surgical treatment of patients with Marfan syndrome remain controversial. It is of utmost importance to identify patients at risk for acute aortic events to establish the correct surgical timing and the appropriate surgical treatment", "The not-uncommon spinal abnormalities associated with Marfan's syndrome rarely undergird clinical problems, and neurological features accompanying such bone abnormalities are rare.", "The major cardiovascular manifestations of this condition are aortic dilation, which may involve the proximal and distal aorta, aortic regurgitation, aortic dissection, mitral valve prolapse, and mitral regurgitation. ", "For the first time Bernhard Marfan described the Marfan-Syndrome in 1896; it is a meso- and ectodermed variety with the conducting symptom of \"arachnodactyly\".", "Initial physical examination revealed an aortic systolic murmur and musculoskeletal morphological abnormalities compatible with Marfan syndrome", "Marfan syndrome is a multisystemic connective tissue disorder caused mainly by mutations in the fibrillin-1 gene. The entire cardiovascular system is affected in patients with Marfan syndrome. Aortic root dilatation, aortic valve regurgitation or - the most feared and life-threatening symptom - aortic root dissection are the most common manifestations.", "Meningeal abnormalities such as dural ectasia are seen in Marfan syndrome, but spinal meningeal cysts are rarely seen.", "Pathohistological alterations of the aorta in patients with Marfan syndrome consisted in pronounced restructuring of the wall with deep irreversible alternative changes. ", "The characteristics of acute aortic dissection among young Chinese patients: a comparison between Marfan syndrome and non-Marfan syndrome patients.", "The main objective of this trial is to assess whether losartan treatment leads to a clinically relevant decrease of aortic dilatation in adult patients with Marfan syndrome.", "During a 16-year period, 300 patients with presumed Marfan syndrome underwent 398 operations on the aorta and branch arteries, including 125 aortic root operations, 59 aortic arch repairs, 31 descending thoracic aortic repairs, and 178 thoracoabdominal aortic repairs.", "Aortic disease in patients with Marfan syndrome: aortic volume assessment for surveillance", "To compare the clinical features of type A aortic dissection (AAD) in patients with Marfan syndrome (MFS) and bicuspid aortic valves (BAV)", "Impairment of flow-mediated dilation correlates with aortic dilation in patients with Marfan syndrome" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/25490352", "http://www.ncbi.nlm.nih.gov/pubmed/23941798", "http://www.ncbi.nlm.nih.gov/pubmed/24721296", "http://www.ncbi.nlm.nih.gov/pubmed/23877552", "http://www.ncbi.nlm.nih.gov/pubmed/1464550", "http://www.ncbi.nlm.nih.gov/pubmed/21958999", "http://www.ncbi.nlm.nih.gov/pubmed/20067609", "http://www.ncbi.nlm.nih.gov/pubmed/3392569", "http://www.ncbi.nlm.nih.gov/pubmed/10147800", "http://www.ncbi.nlm.nih.gov/pubmed/23852405", "http://www.ncbi.nlm.nih.gov/pubmed/19430557", "http://www.ncbi.nlm.nih.gov/pubmed/16731131", "http://www.ncbi.nlm.nih.gov/pubmed/22397493", "http://www.ncbi.nlm.nih.gov/pubmed/23801775", "http://www.ncbi.nlm.nih.gov/pubmed/19216964" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013577", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D008382", "http://www.disease-ontology.org/api/metadata/DOID:14323", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D010361" ]

[ "Tetrodotoxin (TTX) is a low molecular weight (approximately 319 Da) neurotoxin found in a number of animal species, including pufferfish. TTX is originally produced by marine bacteria, and pufferfish are intoxicated through the food chain that starts with the bacteria. TTX is found in warm waters, especially of the Indian and Pacific Oceans. TTX poisoning due to marine snails has recently spread through Japan, China, Taiwan, and Europe." ]

[]

[ "The selling and importing of puffer fish species and their products was banned in Thailand in 2002, because of possible neurotoxic effects.", "Efficiency of a rapid test for detection of tetrodotoxin in puffer fish.", "Marine pufferfish contain tetrodotoxin (TTX), an extremely potent neurotoxin", "Tetrodotoxin is a potent low weight marine toxin found in warm waters, especially of the Indian and Pacific Oceans. Intoxications are usually linked to the consumption of the puffer fish, although TTX was already detected in several different edible taxa.", "Food poisoning due to ingestion of a puffer fish occurred in Nagasaki Prefecture, Japan, in October 2008, causing neurotoxic symptoms similar to those of tetrodotoxin (TTX) poisoning.", " Our findings raised a concern for people, not only Thais but also inhabitants of other countries situated on the Andaman coast; consuming puffers of the Andaman seas is risky due to potential TTX intoxication.", "Toxic marine puffer fish in Thailand seas and tetrodotoxin they contained.", "Puffer fish, Takifugu niphobles, collected from the Hong Kong coastal waters were screened for tetrodotoxin-producing bacteria. A Gram-negative, non-acid-fast, non-sporing and rod shaped bacterial strain (designated as gutB01) was isolated from the intestine of the puffer fish and was shown to produce tetrodotoxin (TTX)", "Isolation and identification of a new tetrodotoxin-producing bacterial species, Raoultella terrigena, from Hong Kong marine puffer fish Takifugu niphobles.", "Green toadfish Lagocephalus lunaris inhabits tropical and subtropical seas and contains high tetrodotoxin (TTX) levels in the muscle as well as liver and gonad", "Tetrodotoxin (TTX) is a highly potent neurotoxin that blocks the action potential by selectively binding to voltage-gated sodium channels (Na(v))", "Suspected tetrodotoxin (TTX) poisoning was associated with eating unknown fish in April 2009 in Taiwan", "Marine pufferfish generally contain a large amount of tetrodotoxin (TTX) in their skin and viscera, and have caused many incidences of food poisoning, especially in Japan.", " TTX is originally produced by marine bacteria, and pufferfish are intoxicated through the food chain that starts with the bacteria. ", ", TTX poisoning due to marine snails has recently spread through Japan, China, Taiwan, and Europe.", "The inhibitory effects of toxin extracted from muscle or liver of five different puffer fishes (hereafter referred as puffer(s)) captured on the Japanese sea coast ", "LC/MS analysis of tetrodotoxin and its deoxy analogs in the marine puffer fish Fugu niphobles from the southern coast of Korea, and in the brackishwater puffer fishes Tetraodon nigroviridis and Tetraodon biocellatus from Southeast Asia.", "Toxins such as saxitoxins, tetrodotoxin, palytoxin, nodularin, okadaic acid, domoic acid, may be produced in large amounts by dinoflagellates, cyanobacteria, bacteria and diatoms and accumulate in vectors that transfer the toxin along food chains", "Tetrodotoxin (TTX) is a low molecular weight (approximately 319 Da) neurotoxin found in a number of animal species, including pufferfish." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/22163191", "http://www.ncbi.nlm.nih.gov/pubmed/22069694", "http://www.ncbi.nlm.nih.gov/pubmed/20479966", "http://www.ncbi.nlm.nih.gov/pubmed/22690139", "http://www.ncbi.nlm.nih.gov/pubmed/23724281", "http://www.ncbi.nlm.nih.gov/pubmed/24279996", "http://www.ncbi.nlm.nih.gov/pubmed/24295175", "http://www.ncbi.nlm.nih.gov/pubmed/22028709", "http://www.ncbi.nlm.nih.gov/pubmed/20161971", "http://www.ncbi.nlm.nih.gov/pubmed/20637221", "http://www.ncbi.nlm.nih.gov/pubmed/20411115", "http://www.ncbi.nlm.nih.gov/pubmed/22688023", "http://www.ncbi.nlm.nih.gov/pubmed/21734837", "http://www.ncbi.nlm.nih.gov/pubmed/21549050" ]

[ { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A0463937", "o": "DXplain" }, { "p": "http://www.w3.org/2008/05/skos-xl#prefLabel", "s": "http://linkedlifedata.com/resource/umls/id/C0275142", "o": "http://linkedlifedata.com/resource/umls/label/A0463937" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A0463937", "o": "TETRODOTOXIN POISONING" }, { "p": "http://linkedlifedata.com/resource/pubmed/registryNumber", "s": "http://linkedlifedata.com/resource/pubmed/chemical/Tetrodotoxin", "o": "4368-28-9" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://linkedlifedata.com/resource/pubmed/chemical/Tetrodotoxin", "o": "Tetrodotoxin" }, { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A0366686", "o": "MeSH" }, { "p": "http://linkedlifedata.com/resource/umls/prefMetaMap", "s": "http://linkedlifedata.com/resource/umls/id/C0208311", "o": "http://linkedlifedata.com/resource/umls/label/A0366687" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A0366686", "o": "Tetrodotoxin, (4beta)-" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C0208311", "o": "http://linkedlifedata.com/resource/umls/label/A0366686" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A0366687", "o": "4-epitetrodotoxin" }, { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A0366687", "o": "MeSH" } ]

[ "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013779", "http://www.biosemantics.org/jochem#4053979", "http://www.biosemantics.org/jochem#4274648" ]

[ "Myotonic dystrophy (DM) is a heterogeneous neuromuscular disease with an autosomal dominant pattern of inheritance." ]

[ "autosomal dominant" ]

[ "Myotonic dystrophy type 2 (DM2) is an autosomal dominant, multisystem disorder caused by a CCTG tetranucleotide repeat expansion located in intron 1 of the zinc finger protein 9 gene (ZNF9 gene) on chromosome 3q 21.3.", "Myotonic dystrophy type 1 (DM1) is an autosomal dominant disorder, caused by an expansion of a CTG triplet repeat in the DMPK gene.", "Myotonic dystrophy (DM), the most common form of muscular dystrophy in adults, is a clinically and genetically heterogeneous neuromuscular disorder. DM is characterized by autosomal dominant inheritance, muscular dystrophy, myotonia, and multisystem involvement. Type 1 DM (DM1) is caused by a (CTG)(n) expansion in the 3' untranslated region of DMPK in 19q13.3.", "proximal myotonic myopathy (PROMM) and type 2 DM (DM2) but without the DM1 mutation, showed linkage to the 3q21 region and were recently shown to segregate a (CCTG)(n) expansion mutation in intron 1 of ZNF9.", "All patients have the DM2 (CCTG)(n) expansion.", "Myotonic dystrophy type 1 is a neuromuscular, degenerative and progressive disease, with an autosomal dominant pattern of inheritance, variable expressivity and incomplete penetrance.", "The worldwide intergenerational behavior of the DM1 mutation is similar in Costa Rica", "Dystrophic myotonia is a sufficiently rare disease inherited mainly by the autosomal dominant type." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/12577208", "http://www.ncbi.nlm.nih.gov/pubmed/12970845", "http://www.ncbi.nlm.nih.gov/pubmed/8154209", "http://www.ncbi.nlm.nih.gov/pubmed/18228241", "http://www.ncbi.nlm.nih.gov/pubmed/22332444" ]

[ { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A1189440", "o": "myotonic dystrophy" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A12058083", "o": "Myotonic Dystrophy" }, { "p": "http://www.w3.org/2008/05/skos-xl#prefLabel", "s": "http://linkedlifedata.com/resource/umls/id/C0027126", "o": "http://linkedlifedata.com/resource/umls/label/A12058083" } ]

[ "http://www.disease-ontology.org/api/metadata/DOID:11722", "http://www.disease-ontology.org/api/metadata/DOID:655", "http://www.disease-ontology.org/api/metadata/DOID:9884", "http://www.disease-ontology.org/api/metadata/DOID:450" ]

[ "HBS1L-MYB intergenic variants modulate fetal hemoglobin via long-range MYB enhancers. Several HBS1L-MYB intergenic variants affect regulatory elements that are occupied by key erythroid transcription factors within this region. These elements interact with MYB, a critical regulator of erythroid development and HbF levels. Several HBS1L-MYB intergenic variants reduce transcription factor binding, affecting long-range interactions with MYB and MYB expression levels." ]

[]

[ "HBS1L-MYB intergenic variants modulate fetal hemoglobin via long-range MYB enhancers.", "Here, we determined that several HBS1L-MYB intergenic variants affect regulatory elements that are occupied by key erythroid transcription factors within this region. These elements interact with MYB, a critical regulator of erythroid development and HbF levels. We found that several HBS1L-MYB intergenic variants reduce transcription factor binding, affecting long-range interactions with MYB and MYB expression levels. These data provide a functional explanation for the genetic association of HBS1L-MYB intergenic polymorphisms with human erythroid traits and HbF levels. Our results further designate MYB as a target for therapeutic induction of HbF to ameliorate sickle cell and β-thalassemia disease severity." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/24614105" ]

[ { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A0067026", "o": "D006454" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A0067106", "o": "D006454" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A0058894", "o": "D005319" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A0067093", "o": "D005319" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A0067060", "o": "D005319" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A0067059", "o": "D005319" } ]

[ "http://www.biosemantics.org/jochem#4257620", "http://www.uniprot.org/uniprot/HBBF_CAPHI", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D020570", "http://www.biosemantics.org/jochem#4256386", "http://www.uniprot.org/uniprot/MYB_BOVIN", "http://www.uniprot.org/uniprot/MYB_CHICK", "http://www.biosemantics.org/jochem#4265352", "http://www.biosemantics.org/jochem#4249310", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D020598", "http://www.uniprot.org/uniprot/MYB_HUMAN", "http://www.uniprot.org/uniprot/HBS1L_HUMAN", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D006454", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D006441", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D006442", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D006443", "http://www.biosemantics.org/jochem#4259159", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D020626", "http://www.uniprot.org/uniprot/HBBF_BOVIN", "http://www.uniprot.org/uniprot/HBS1L_PONAB", "http://www.biosemantics.org/jochem#4249395", "http://amigo.geneontology.org/amigo/term/GO:0020027", "http://www.uniprot.org/uniprot/HBS1L_BOVIN", "http://amigo.geneontology.org/amigo/term/GO:0042540", "http://amigo.geneontology.org/amigo/term/GO:0031523", "http://amigo.geneontology.org/amigo/term/GO:0020028", "http://www.biosemantics.org/jochem#4264470", "http://www.biosemantics.org/jochem#4259595", "http://www.uniprot.org/uniprot/HBBF_SHEEP", "http://www.biosemantics.org/jochem#4256471", "http://www.uniprot.org/uniprot/HBB1_TRICR", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005319", "http://www.biosemantics.org/jochem#4264315" ]

[ "There are two mammalian orthologs of Yki: YAP and TAZ" ]

[ "YAP", "TAZ" ]

[ "Yorkie ortholog YAP", "Yorkie ortholog, Yap1", "human ortholog of Yorkie, YAP", "YAP1, the ortholog of Drosophila Yorkie", "Yorkie ortholog YAP", " Yorkie homolog YAP", "Yki (YAP/TAZ in vertebrates" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/17980593", "http://www.ncbi.nlm.nih.gov/pubmed/18413746", "http://www.ncbi.nlm.nih.gov/pubmed/23484853", "http://www.ncbi.nlm.nih.gov/pubmed/22898666", "http://www.ncbi.nlm.nih.gov/pubmed/23985272", "http://www.ncbi.nlm.nih.gov/pubmed/22101275", "http://www.ncbi.nlm.nih.gov/pubmed/19878874" ]

[]

[ "http://www.uniprot.org/uniprot/YORKI_DROME" ]

[ "Statin use after subarachnoid hemorrhage has been shown be associated with improved outcomes by some prospective clinical trials. It has been reported that statin use after subarachnoid hemorrhage reduced rates of vasospasm, delayed cerebral ischemia, and mortality. However, other authors have failed to find beneficial effect of statin use in subarachnoid hemorrhage patients." ]

[ "yes" ]

[ "Statins have been shown in two recent small phase I/II trials to be associated with a marked reduction in clinical and transcranial Doppler (TCD) evidence of vasospasm after aneurysmal subarachnoid haemorrhage (SAH). ", "Statins did not result in reduced TCD velocities, clinical or angiographic vasospasm, or improvements in global outcome at the time of hospital discharge. ", "There remains significant uncertainty as to the role of statins in preventing vasospasm after SAH.", "Although the results of 2 randomized clinical trials demonstrated that statin decreases the incidence of symptomatic cerebral vasospasm after aSAH, retrospective studies have failed to confirm this.", "There were no differences in the incidence of symptomatic vasospasm (25.3 vs 30.5%; p = 0.277), in-hospital mortality rate (18 vs 15%; p = 0.468), length of hospitalization (21 +/- 15 vs 19 +/- 12 days; p = 0.281), or poor outcome at discharge (Glasgow Outcome Scale Scores 1-2: 21.7 vs 18.2%; p = 0.416) between the simvastatin and nonstatin cohorts. ", "The uniform introduction of simvastatin did not reduce the incidence of symptomatic cerebral vasospasm, death, or poor outcome in patients with aSAH. Simvastatin was well tolerated, but its benefit may be less than has been previously reported.", "Cholesterol-reducing agents might improve unfavourable outcomes.", "We cannot draw any conclusions about the effectiveness and safety of lowering cholesterol in aneurysmal SAH because of insufficient reliable evidence from only one small trial.", "Experimental evidence has indicated the benefit of simvastatin in the treatment of subarachnoid hemorrhage.", "There was an improvement in the functional outcome in the simvastatin group at 1, 3 or 6 months in the follow-up; however, this difference was not statistically significant.", " There was benefit of simvastatin in terms of reduction in clinical vasospasm, mortality or improved functional outcome, however, this was not statistically significant.", "Cerebral vasomotor reactivity, however, is significantly improved after long-term statin administration in most patients with severe small vessel disease, aneurysmal subarachnoid hemorrhage, or impaired baseline CA.", "Atorvastatin decreases computed tomography and S100-assessed brain ischemia after subarachnoid aneurysmal hemorrhage: a comparative study.", "In the overall population, cerebral vasospasm was significantly less common in the statin-treated group. Severity of vasospasm, as assessed on the most severe angiogram, was lowered with statin. Statins significantly reduced volume of ischemia in patients with vasospasm and an uncomplicated coiling procedure. S100B levels were significantly lower in statin-treated patients, and the decrease was greatest among high-grade patients (World Federation of Neurological Surgeons 3-5). No differences were found between statin-treated and untreated groups regarding rescue therapy intensity or 1-yr clinical outcomes.", "Atorvastatin reduces the incidence, the severity and the ischemic consequences of vasospasm as assessed on computed tomography. In high-grade World Federation of Neurological Surgeons patients, atorvastatin decreases serum levels of S100B, a biomarker of brain ischemia. Despite these positive effects on biomarkers, no improvement of outcome was seen in the overall population, although there was a tendency for a better clinical outcome in high-grade patients.", "3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, or statins, have been associated with improved clinical outcomes after ischemic stroke and subarachnoid hemorrhage, but with an increased risk of incidental spontaneous intracerebral hemorrhage (ICH).", "Statins are known to have pleiotropic vascular effects, some of which may interrupt the pathogenesis of DNDs. Based on promising preliminary reports, many clinicians routinely administer statins to prevent DNDs.", "However, observational studies have not revealed an association between statin-use and reduced DNDs or improved neurological outcomes. Results of RCTs have been inconsistent and limited by small sample size, but together suggest that statins may reduce DNDs, with no clear impact on mortality or neurological recovery.", "the role of statins in the management of patients with SAH remains unclear. Although promising, statins should not, at this time, be considered standard care.", "In patients with SAH, they may decrease the incidence of symptomatic vasospasm, although the effects on overall outcome are less clear.", "Statins treatment may have potential clinical impact in vascular disease beyond cholesterol lowering. Its benefits have been documented in cerebral ischaemia and in subarachnoid haemorrhage.", "A recent meta-analysis investigating the efficacy of statin treatment in patients with aneurysmal subarachnoid hemorrhage reported a reduced incidence of vasospasm, delayed cerebral ischemia, and mortality in statin-treated patients.", "The results of the present systematic review do not lend statistically significant support to the finding of a beneficial effect of statins in patients with aneurysmal subarachnoid hemorrhage as reported in a previous meta-analysis.", "Pre-treatment with cholesterol lowering drugs of the statin family may exert protective effects in patients with ischaemic stroke and subarachnoid haemorrhage but their effects are not clear in patients with intracerebral haemorrhage (ICH). ", "Recently, two randomized controlled phase II studies showed that acute initiation of statin treatment directly after aneurysmal subarachnoid hemorrhage (SAH) decreases the incidence of radiologic vasospasm and clinical signs of delayed cerebral ischemia (DCI), and even reduces mortality.", "We conclude that both the primary and secondary outcome results of this study do not support a beneficial effect of simvastatin in patients with SAH.", "Novel uses of their anti-inflammatory properties in sepsis and vasomotor properties in subarachnoid haemorrhage are being further investigated by randomised trials.", "A trend towards a lower mortality within 14 days in patients receiving solely simvastatin and those receiving statin and magnesium as compared with the control group was found. ", "Initiation of statin therapy after aneurysmal SAH significantly reduces the incidence of vasospasm, delayed ischemic deficits, and mortality.", "The addition of statins to standard care was not associated with any reduction in the development of vasospasm or improvement in outcomes after aneurysmal subarachnoid hemorrhage. ", "We have previously demonstrated that acute pravastatin therapy after aneurysmal subarachnoid hemorrhage ameliorates vasospasm-related delayed ischemic deficits.", " This trial demonstrates that acute statin treatment reduces traditional rescue therapy for vasospasm after aneurysmal subarachnoid hemorrhage. Improvement in early outcome has proved robust at 6 months, particularly in relation to physical and psychosocial (Short Form 36) outcome.", "The authors previously have demonstrated that acute treatment with pravastatin after aneurysmal subarachnoid hemorrhage (SAH) can ameliorate vasospasm-related delayed ischemic neurological deficits (DINDs).", "The neuroprotective effects of acute treatment with pravastatin following aneurysmal SAH are associated with enhancement of autoregulation", "Simvastatin reduces vasospasm after aneurysmal subarachnoid hemorrhage: results of a pilot randomized clinical trial.", "The use of simvastatin as prophylaxis against delayed cerebral ischemia after aneurysmal SAH is a safe and well-tolerated intervention. Its use attenuates serum markers associated with brain injury and decreases the incidence of radiographic vasospasm and delayed ischemic deficit.", "Acute treatment with pravastatin after aSAH is safe and ameliorates cerebral vasospasm, improves cerebral autoregulation, and reduces vasospasm-related DID.", " SAH statin users demonstrated significant improvement in 14-day functional outcome, a significantly lower incidence of DCI and cerebral infarctions of any type, as well as prevention of TCD highest mean velocity elevation. However, we did not find a significant statin impact on mortality or global outcome (Modified Rankin Scale) in this small sample. " ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/16051891", "http://www.ncbi.nlm.nih.gov/pubmed/19875741", "http://www.ncbi.nlm.nih.gov/pubmed/19614959", "http://www.ncbi.nlm.nih.gov/pubmed/24323051", "http://www.ncbi.nlm.nih.gov/pubmed/19439205", "http://www.ncbi.nlm.nih.gov/pubmed/23392270", "http://www.ncbi.nlm.nih.gov/pubmed/23298376", "http://www.ncbi.nlm.nih.gov/pubmed/19458605", "http://www.ncbi.nlm.nih.gov/pubmed/16049199", "http://www.ncbi.nlm.nih.gov/pubmed/22709377", "http://www.ncbi.nlm.nih.gov/pubmed/20934152", "http://www.ncbi.nlm.nih.gov/pubmed/19199459", "http://www.ncbi.nlm.nih.gov/pubmed/19231192", "http://www.ncbi.nlm.nih.gov/pubmed/23633351", "http://www.ncbi.nlm.nih.gov/pubmed/19912325", "http://www.ncbi.nlm.nih.gov/pubmed/18382320", "http://www.ncbi.nlm.nih.gov/pubmed/18658040", "http://www.ncbi.nlm.nih.gov/pubmed/23691312", "http://www.ncbi.nlm.nih.gov/pubmed/22929438", "http://www.ncbi.nlm.nih.gov/pubmed/17413047", "http://www.ncbi.nlm.nih.gov/pubmed/17029334", "http://www.ncbi.nlm.nih.gov/pubmed/21125471", "http://www.ncbi.nlm.nih.gov/pubmed/21926584", "http://www.ncbi.nlm.nih.gov/pubmed/18691455", "http://www.ncbi.nlm.nih.gov/pubmed/19197830", "http://www.ncbi.nlm.nih.gov/pubmed/21556312", "http://www.ncbi.nlm.nih.gov/pubmed/17986515", "http://www.ncbi.nlm.nih.gov/pubmed/15730572", "http://www.ncbi.nlm.nih.gov/pubmed/21755120" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D019161", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013345", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D017063", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D010043" ]

[ "Microtubules are highly anisotropic structures built from tubulin heterodimers. They are hollow cylindrical shells with a ∼ 25 nm (24nm - 25nm) outer diameter." ]

[ "24nm - 25 nm" ]

[ "microtubules are highly anisotropic structures built from tubulin heterodimers. They are hollow cylindrical shells with a ∼ 25 nm outer diameter", "single microtubules (diameter 25 nm", "The individual microtubules measured about 24 nm in outer diameter", "Microtubules are hollow tubes some 25 nm in diameter participating in the eukaryotic cytoskeleton.", "Microtubule assembly is accompanied by hydrolysis of GTP associated with beta-tubulin so that microtubules consist principally of \"GDP-tubulin\" stabilized by a short \"GTP cap.\" Microtubules are polar, cylindrical structures some 25 nm in diameter.", "They are hollow cylindrical shells with a ∼ 25 nm outer diameter and are tens of microns long", "Microtubule assembly is accompanied by hydrolysis of GTP associated with beta-tubulin so that microtubules consist principally of \"GDP-tubulin\" stabilized by a short \"GTP cap.\" Microtubules are polar, cylindrical structures some 25 nm in diameter", "Microtubules are hollow tubes some 25 nm in diameter participating in the eukaryotic cytoskeleton" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/19565362", "http://www.ncbi.nlm.nih.gov/pubmed/7161484", "http://www.ncbi.nlm.nih.gov/pubmed/23145817", "http://www.ncbi.nlm.nih.gov/pubmed/23729907", "http://www.ncbi.nlm.nih.gov/pubmed/9549038", "http://www.ncbi.nlm.nih.gov/pubmed/18085218" ]

[]

[ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0005874", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0045298" ]

[ "Yes, molindone has a tendency to cause weight loss or limited weight gain." ]

[ "yes" ]

[ "Mean weight increased by 0.54 kg, and mean body mass index by 0.24 kg/m(2). ", "A large-scale trial comparing a first-generation antipsychotic (molindone) with newer agents did not find significant differences in treatment response, although the newer antipsychotics were associated with more severe weight gain. ", "No agent demonstrated superior efficacy, and all were associated with side effects, including weight gain. ", "The three treatment arms did not significantly differ in symptom decrease or time to discontinuation. Akathisia was more common with molindone and elevated prolactin concentrations more common with risperidone. Although weight gain and metabolic adverse events had occurred more often with olanzapine and risperidone during the acute trial, no significant between-drug differences emerged in most of these parameters during maintenance treatment. ", "Olanzapine and risperidone were associated with significantly greater weight gain. Olanzapine showed the greatest risk of weight gain and significant increases in fasting cholesterol, low density lipoprotein, insulin, and liver transaminase levels. Molindone led to more self-reports of akathisia. ", "Molindone is no more or less likely than typical drugs to cause movement disorders, but it does cause significantly more weight loss (2RCTs n=60 RR 2.78, CI 1.10 to 6.99, NNH 5 CI 2 to 77). ", "Molindone may be an effective antipsychotic but its adverse effect profile does not differ significantly from that of typical antipsychotics (apart from the event of weight loss). ", "Convergent evidence suggests a hierarchy in the magnitude of BWG that may be induced by diverse agents, being very high for clozapine and olanzapine; high for quetiapine, zotepin, chlorpromazine, and thioridazine; moderate for risperidone and sertindole; and low for ziprazidone, amisulpiride, haloperidol, fluphenazine, pimozide, and molindone. ", "Loxapine and molindone induce weight decreases, and these exceptions are difficult to explain.", "It is no more or less likely than typical drugs to cause movement disorders, but causes significantly more weight loss (RR 2.78, CI 1.10 to 6.99).", "Molindone may be an effective antipsychotic; however, its adverse effect profile does not differ significantly from that of typical antipsychotics, apart from the event of weight loss. ", "Among conventional agents, mean weight change ranged from a reduction of 0.39 kg with molindone to an increase of 3.19 kg with thioridazine.", "Weight gain has been reported with nearly every antipsychotic drug on the market (molindone is an exception). ", "Although almost all antipsychotics induce bodyweight gain, molindone and loxapine appear to induce bodyweight loss. ", "Clozapine and low-potency phenothiazines are associated with the largest gains and molindone with weight loss, but the mechanism is not known. ", "On average, molindone patients lost 5 pounds over the 6 weeks of treatment, whereas thioridazine patients gained 6 pounds. ", "Clinically, molindone has a tendency to cause weight loss and may have less effect on seizure threshold than conventional antipsychotic agents", " Monthly weights and neuroleptic dosages during the first three months of psychiatric hospitalization were compared between matched groups of patients receiving molindone, a combination of molindone and other neuroleptics, or other neuroleptic drugs. We found no significant differences in weight gain among the three groups. ", "The weight-reducing property of molindone, a recently introduced antipsychotic drug, was tested in 9 hospitalized chronic schizophrenic patients. There was an average weight loss of 7.6 kg after 3 months on molindone; most of the loss occurred during the first month." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/10548138", "http://www.ncbi.nlm.nih.gov/pubmed/2671060", "http://www.ncbi.nlm.nih.gov/pubmed/3780420", "http://www.ncbi.nlm.nih.gov/pubmed/8800628", "http://www.ncbi.nlm.nih.gov/pubmed/20502331", "http://www.ncbi.nlm.nih.gov/pubmed/8290673", "http://www.ncbi.nlm.nih.gov/pubmed/22372512", "http://www.ncbi.nlm.nih.gov/pubmed/7481576", "http://www.ncbi.nlm.nih.gov/pubmed/18794207", "http://www.ncbi.nlm.nih.gov/pubmed/11488257", "http://www.ncbi.nlm.nih.gov/pubmed/12518268", "http://www.ncbi.nlm.nih.gov/pubmed/10553730", "http://www.ncbi.nlm.nih.gov/pubmed/17253473", "http://www.ncbi.nlm.nih.gov/pubmed/20494268", "http://www.ncbi.nlm.nih.gov/pubmed/10796464", "http://www.ncbi.nlm.nih.gov/pubmed/842709" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D015431", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D015430", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D008972", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001836", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001837", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001835", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D019440", "http://www.biosemantics.org/jochem#4249624" ]

[ "Mutations in the PCCA or PCCB genes, encoding both subunits of propionyl-CoA carboxylase." ]

[]

[ "utations in the PCCA or PCCB genes coding for alpha and beta subunits of propionyl CoA carboxylase can cause propionic acidemia", "propionic acidemia (PA) can result from mutations in either of the genes PCCA or PCCB, which encode the alpha and beta subunits, respectively, of the mitochondrial enzyme propionyl CoA-carboxylase", "eficiency of propionyl-CoA carboxylase (PCC; alpha 4 beta 4) results in the rare, autosomal recessive disease propionic acidemia", "PA is caused by mutations in either the PCCA or PCCB genes encoding the α- and β-subunits of the PCC enzyme ", "eficiency of propionyl CoA carboxylase (PCC), a dodecamer of alpha and beta subunits, causes inherited propionic acidemia", "Recent studies have identified the genomic mutations in the genes PCCA and PCCB", "ropionic acidemia is an organic acidemia that can lead to metabolic acidosis", "plicing defects account for 16% of the mutant alleles in the PCCA and PCCB genes, encoding both subunits of the propionyl-CoA carboxylase (PCC) enzyme, defective in propionic acidemia", "ropionic acidemia (PA) is an autosomal recessive disorder of metabolism caused by a deficiency of propionyl-coenzyme A carboxylase (PCC)", "In the PA patients, we have identified four different changes in the PCCA gene, including one novel one (c.414+5G>A) affecting the splicing process", "utations in either the PCCA or PCCB genes are responsible for propionic acidemia (PA)", "Propionic acidemia is a common organic acidemia, caused by deficiency of propionyl-CoA carboxylase (PCC), which catalyzes the carboxylation of propionyl-CoA to D-methylmalonyl-CoA. PCC is a dodecameric enzyme of alpha-PCC and beta-PCC subunits, nuclearly encoded by genes PCCA and PCCB, respectively. Mutation in either gene cause propionic acidemia", "PA is inherited in an autosomal recessive fashion involving mutations in PCCA or PCCB encoding the alpha and beta subunits of propionyl-CoA carboxylase (PCC)", "Two siblings affected with propionic acidemia were screened for putative mutations in PCCA and PCCB genes coding alpha and beta subunits of propionyl-coenzyme A (CoA) carboxylase", "ropionic acidemia results from mutations in either of the two genes, PCCA or PCCB, that encode the two subunits of the propionyl-CoA carboxylase (PCC) enzyme", "utations in the PCCA or PCCB genes, encoding both subunits of propionyl-CoA carboxylase, result in propionic acidemia", " we analyze splicing mutations identified in propionic acidemia patients to clarify their functional effects and their involvement in the disease phenotype. Two mutations in the PCCA gene detected in homozygous patients and involving consensus splice sequences ", "An enzyme deficiency can result from mutations in either PCCA or PCCB.", "(PA) is an inborn error of organic acid metabolism caused by a deficiency of propionyl-CoA carboxylase.", "Mutations in either gene cause PA and to date, up to 47 different allelic variations in the PCCB gene have been identified in different population", "ropionic acidemia (PA) is a recessive disorder caused by a deficiency of propionyl-CoA carboxylase (PCC), a dodecameric enzyme composed of two different proteins alpha-PCC and beta-PC", "PCC is a multimeric protein composed of two different alpha- and beta-PCC subunits, nuclearly encoded by the PCCA and PCCB genes, respectively. Mutations in either gene cause the clinically heterogeneous disease propionic acidemia", "More than 24 mutations have been found in the PCCA gene in patients with PA, ", "ropionic acidemia (PA, MIM 232000 and 232050) is caused by a deficiency of mitochondrial biotin-dependent propionyl-CoA carboxylase (PCC, EC 6.4.1.3), a heteropolymeric enzyme composed of alpha and beta subunits, which are encoded by the PCCA and PCCB genes, respectively", "Approximately 60 mutations have been reported in the nuclear genes PCCA and PCCB that encode the two PCC subunits", "eficiency of propionyl-CoA carboxylase (PCC) results in propionic acidemia", "ropionic acidemia can result from mutations in the PCCA or PCCB genes encoding the alpha and beta subunits", "ropionic acidemia is an inherited metabolic disorder caused by deficiency of propionyl-CoA carboxylase, a dodecameric enzyme composed of alpha-PCC and beta-PCC subunits ", "A genetic deficiency of PCC activity causes propionic acidemia, a potentially fatal disease with onset in severe cases in the newborn period. Affected patients may have mutations of either the PCCA or PCCB gene.", "PCC is composed of two equal subunits, alpha and beta, which are encoded by two separate genes at two distinct human loci. Mutations of either gene in humans results in propionic acidemia (PA)", "Deficiency of PCC results in propionic acidemia (PA), a metabolic disorder", " PCC consists of two subunits, alpha and beta, encoded by the PCCA and PCCB genes, respectively. Inherited PCC deficiency due to mutations in either gene results in propionic acidemia (PA),", "mutations in the PCCA and PCCB genes causing propionic acidemia", "Mutations in the PCCA and PCCB genes, which encode the a and b subunits of this heteropolymer, result in propionic acidemia (PA)", "ropionic acidemia is a rare autosomal recessive disorder of intermediary metabolism. It is caused by a deficiency of the mitochondrial enzyme propionyl-CoA carboxylase (PCC, EC 6.4.1.3), a heteropolymeric protein composed of two subunits, alpha and beta", "ropionic acidemia is an autosomal recessive disorder caused by a deficiency in the mitochondrial enzyme propionyl-CoA carboxylase (PCC). PCC is composed of two subunits, alpha and beta, encoded by the PCCA and PCCB genes,", "Propionyl-CoA carboxylase (PCC) is a mitochondrial biotin-dependent enzyme composed of an equal number of alpha and beta subunits. Mutations in the PCCA (alpha subunit) or PCCB (beta subunit) gene can cause the inherited metabolic disease propionic acidemia (PA), which can be life threatening in the neonatal period. Lack of data on the genomic structure of PCCB has been a significant impediment to full characterization of PCCB mutant chromosomes. In this study, we describe the genomic organization of the coding sequence of the human PCCB gene and the characterization of mutations causing PA in a total of 29 unrelated patients-21 from Spain and 8 from Latin America. The implementation of long-distance PCR has allowed us to amplify the regions encompassing the exon/intron boundaries and all the exons. The gene consists of 15 exons of 57-183 bp in size. All splice sites are consistent with the gt/ag rule. The availability of the intron sequences flanking each exon has provided the basis for implementation of screening for mutations in the PCCB gene. A total of 56/58 mutant chromosomes studied have been defined, with a total of 16 different mutations detected. The mutation spectrum includes one insertion/deletion, two insertions, 10 missense mutations, one nonsense mutation, and two splicing defects. Thirteen of these mutations correspond to those not described yet in other populations. The mutation profile found in the chromosomes from the Latin American patients basically resembles that of the Spanish patients.", "Inherited deficiency of PCC due to mutations in either the PCCA or the PCCB gene results in propionic acidemia (PA)", "Mutations of the PCCA (alpha subunit) or PCCB (beta subunit) gene cause the inherited metabolic disease, propionic acidemia", "We have detected three types of mutation in the same exon of the coding sequence of beta-subunit of PCC", "ropionic acidemia is an inborn error of organic acid metabolism caused by deficiency of propionyl-CoA carboxylase", "we have identified two mutations of the PCCB gene in a propionic acidemia patient", "ropionic acidemia is an inherited disorder of organic acid metabolism that is caused by deficiency of propionyl-CoA carboxylase (PCC; EC 6.4.1.3). Affected patients fall into two complementation groups, pccA and pccBC (subgroups B, C, and BC), resulting from deficiency of the nonidentical alpha and beta subunits of PCC", "ropionic acidemia (PA) is an autosomal recessive inborn error", "It is caused by a deficiency of propionyl-CoA carboxylase", "PCC is a heteropolymeric enzyme composed of alpha- and beta-subunits.", "Mutation analysis confirmed the diagnosis of propionic acidemia (PA) with compound heterozygosity for 2 new missense mutations L417W/Q293E in the PCCA gene" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/18790721", "http://www.ncbi.nlm.nih.gov/pubmed/10447268", "http://www.ncbi.nlm.nih.gov/pubmed/19157943", "http://www.ncbi.nlm.nih.gov/pubmed/15235904", "http://www.ncbi.nlm.nih.gov/pubmed/11592820", "http://www.ncbi.nlm.nih.gov/pubmed/12409268", "http://www.ncbi.nlm.nih.gov/pubmed/17051315", "http://www.ncbi.nlm.nih.gov/pubmed/12007220", "http://www.ncbi.nlm.nih.gov/pubmed/12559849", "http://www.ncbi.nlm.nih.gov/pubmed/9683601", "http://www.ncbi.nlm.nih.gov/pubmed/15164333", "http://www.ncbi.nlm.nih.gov/pubmed/21094621", "http://www.ncbi.nlm.nih.gov/pubmed/23053474", "http://www.ncbi.nlm.nih.gov/pubmed/9385377", "http://www.ncbi.nlm.nih.gov/pubmed/8188292", "http://www.ncbi.nlm.nih.gov/pubmed/8023851", "http://www.ncbi.nlm.nih.gov/pubmed/11245989", "http://www.ncbi.nlm.nih.gov/pubmed/12385775", "http://www.ncbi.nlm.nih.gov/pubmed/15059621", "http://www.ncbi.nlm.nih.gov/pubmed/15949719", "http://www.ncbi.nlm.nih.gov/pubmed/21986446", "http://www.ncbi.nlm.nih.gov/pubmed/2154743", "http://www.ncbi.nlm.nih.gov/pubmed/22033733", "http://www.ncbi.nlm.nih.gov/pubmed/15464417", "http://www.ncbi.nlm.nih.gov/pubmed/10502773", "http://www.ncbi.nlm.nih.gov/pubmed/19099776", "http://www.ncbi.nlm.nih.gov/pubmed/11749052", "http://www.ncbi.nlm.nih.gov/pubmed/12757933", "http://www.ncbi.nlm.nih.gov/pubmed/20549364", "http://www.ncbi.nlm.nih.gov/pubmed/11136555", "http://www.ncbi.nlm.nih.gov/pubmed/2095843", "http://www.ncbi.nlm.nih.gov/pubmed/10329019", "http://www.ncbi.nlm.nih.gov/pubmed/11914040", "http://www.ncbi.nlm.nih.gov/pubmed/2249848", "http://www.ncbi.nlm.nih.gov/pubmed/10820128", "http://www.ncbi.nlm.nih.gov/pubmed/20950151", "http://www.ncbi.nlm.nih.gov/pubmed/19025475", "http://www.ncbi.nlm.nih.gov/pubmed/10101253", "http://www.ncbi.nlm.nih.gov/pubmed/9887338" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D056693" ]

[ "Protein phosphatase-1 activity is regulated by two binding partners, inhibitor-1 and the small heat shock protein 20, Hsp20. Cell fractionation, coimmunoprecipitation, and coimmunolocalization studies, revealed an association between Hsp20 and PP1. Small heat shock protein 20 interacts with protein phosphatase-1 and enhances sarcoplasmic reticulum calcium cycling.", "Moreover, protein phosphatase-1 activity is regulated by two binding partners, inhibitor-1 and the small heat shock protein 20, Hsp20. Small heat shock protein 20 interacts with protein phosphatase-1 and enhances sarcoplasmic reticulum calcium cycling." ]

[ "Protein phosphatase 1", "PP1" ]

[ " Moreover, protein phosphatase-1 activity is regulated by two binding partners, inhibitor-1 and the small heat shock protein 20, Hsp20. Indeed, human genetic variants of inhibitor-1 (G147D) or Hsp20 (P20L) result in reduced binding and inhibition of protein phosphatase-1, suggesting aberrant enzymatic regulation in human carriers. ", "Small heat shock protein 20 interacts with protein phosphatase-1 and enhances sarcoplasmic reticulum calcium cycling.", " Hsp20 overexpression in intact animals resulted in significant enhancement of cardiac function, coupled with augmented Ca cycling and sarcoplasmic reticulum Ca load in isolated cardiomyocytes. This was associated with specific increases in phosphorylation of phospholamban (PLN) at both Ser16 and Thr17, relieving its inhibition of the apparent Ca affinity of SERCA2a. Accordingly, the inotropic effects of Hsp20 were abrogated in cardiomyocytes expressing nonphosphorylatable PLN (S16A/T17A). Interestingly, the activity of type 1 protein phosphatase (PP1), a known regulator of PLN signaling, was significantly reduced by Hsp20 overexpression, suggesting that the Hsp20 stimulatory effects are partially mediated through the PP1-PLN axis. This hypothesis was supported by cell fractionation, coimmunoprecipitation, and coimmunolocalization studies, which revealed an association between Hsp20, PP1, and PLN.", "Hsp20 is a novel regulator of sarcoplasmic reticulum Ca cycling by targeting the PP1-PLN axis. These findings, coupled with the well-recognized cardioprotective role of Hsp20, suggest a dual benefit of targeting Hsp20 in heart disease.", "Moreover, protein phosphatase-1 activity is regulated by two binding partners, inhibitor-1 and the small heat shock protein 20, Hsp20.", "Moreover, protein phosphatase-1 activity is regulated by two binding partners, inhibitor-1 and the small heat shock protein 20, Hsp20" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/24244723", "http://www.ncbi.nlm.nih.gov/pubmed/21493896" ]

[]

[ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0016791", "http://www.uniprot.org/uniprot/HSP20_NIPBR" ]

[ "Severe congenital neutropenia is a rare hematological condition causing severe chronic neutropenia. Treatment with the myeloid growth factor, granulocyte-colony stimulating factor (G-CSF) is usually effective, but the dose of G-CSF required to normalize blood neutrophils varies greatly. Ten to thirty percent of the patients evolve to develop acute myeloid leukemia or myelodysplastic syndromes, necessitating careful clinical monitoring." ]

[]

[ "We obtained serial hematopoietic samples from an SCN patient who developed AML 17 years after the initiation of G-CSF treatment. Next- generation sequencing was performed to identify mutations during disease progression. In the AML phase, we found 12 acquired nonsynonymous mutations. Three of these, in CSF3R, LLGL2, and ZC3H18, co-occurred in a subpopulation of progenitor cells already in the early SCN phase. This population expanded over time, whereas clones harboring only CSF3R mutations disappeared from the BM. The other 9 mutations were only apparent in the AML cells and affected known AML-associated genes (RUNX1 and ASXL1) and chromatin remodelers (SUZ12 and EP300). In addition, a novel CSF3R mutation that conferred autonomous proliferation to myeloid progenitors was found. We conclude that progression from SCN to AML is a multistep process, with distinct mutations arising early during the SCN phase and others later in AML development. The sequential gain of 2 CSF3R mutations implicates abnormal G-CSF signaling as a driver of leukemic transformation in this case of SCN", "This chapter focuses on cyclic and congenital neutropenia, two very interesting and rare hematological conditions causing severe chronic neutropenia. Both disorders respond well to treatment with the myeloid growth factor, granulocyte colony-stimulating factor (G-CSF)", "Treatment with G-CSF is usually effective, but the dose of G-CSF required to normalize blood neutrophils varies greatly. Ten to thirty percent of severe congenital neutropenia patients evolve to develop acute myeloid leukemia, necessitating careful clinical monitoring.", "In severe congenital neutropenia (SCN), long-term therapy with granulocyte colony-stimulating factor (G-CSF) has reduced mortality from sepsis, revealing an underlying predisposition to myelodysplastic syndrome and acute myeloid leukaemia (MDS/AML)", "Granulocyte colony-stimulating factor (G-CSF) therapy has significantly reduced the frequency and severity of infections, but its possible influence on the risk of malignancy is not known", "No septic deaths occurred during G-CSF therapy. Thirteen cases of MDS/AL were recorded. The cumulative incidence of MDS/AL was 2.7% (SD 1.3%) at 10 years and 8.1% (SD 2.7%) at 20 years", "Owing to their particular susceptibility to infections, patients with severe congenital neutropenia had the strongest exposure to G-CSF; the risk of leukemia increased with the degree of G-CSF exposure in this subgroup", "Stable long-term risk of leukaemia in patients with severe congenital neutropenia maintained on G-CSF therapy.", "This specifically applies to children with severe congenital neutropenia who receive lifelong treatment with G-CSF and in which the high susceptibility to develop MDS and acute myeloid leukemia (AML) has now become a major clinical concern.", "Owing to their particular susceptibility to infections, patients with severe congenital neutropenia had the strongest exposure to G-CSF; the risk of leukemia increased with the degree of G-CSF exposure in this subgroup.", "As of January 1, 2000, myelodysplasia (MDS) or acute myelogenous leukemia (AML) has occurred in 35 of 387 patients with congenital neutropenia with a cumulative risk of 13% after 8 years of G-CSF treatment" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/15642668", "http://www.ncbi.nlm.nih.gov/pubmed/20456363", "http://www.ncbi.nlm.nih.gov/pubmed/20237318", "http://www.ncbi.nlm.nih.gov/pubmed/22371884", "http://www.ncbi.nlm.nih.gov/pubmed/21052952", "http://www.ncbi.nlm.nih.gov/pubmed/12555210" ]

[]

[ "http://www.biosemantics.org/jochem#4250245", "http://www.disease-ontology.org/api/metadata/DOID:0050590", "http://www.uniprot.org/uniprot/CSF3_CANFA" ]

[ "Neurostimulation of globus pallidus internus is effective for treatment of dystonia. Ventral intermediate thalamic nucleus has also been tested for neurostimulation in dystonia patients." ]

[ "globus pallidus internus" ]

[ "Bilateral globus pallidus internus (GPi) DBS was performed in five SD patients and unilateral ventralis oralis anterior and posterior (Voa/Vop) nucleus of the thalamus DBS in two post-stroke hemiballismus patients. ", "BACKGROUND: Deep brain stimulation of the internal pallidum (GPi-DBS) is effective for various types of drug-refractory primary dystonias. ", "METHODS: In the parent trial, 40 patients were randomly assigned to either sham neurostimulation or neurostimulation of the internal globus pallidus for a period of 3 months and thereafter all patients completed 6 months of active neurostimulation. 38 patients agreed to be followed up annually after the activation of neurostimulation, including assessments of dystonia severity, pain, disability, and quality of life.", "INTERPRETATION: 3 years and 5 years after surgery, pallidal neurostimulation continues to be an effective and relatively safe treatment option for patients with severe idiopathic dystonia. This long-term observation provides further evidence in favour of pallidal neurostimulation as a first-line treatment for patients with medically intractable, segmental, or generalised dystonia.", "We describe a patient who received bilateral globus pallidus internus DBS for dystonia with initially good clinical response, but the device eventually failed. ", "Bilateral pallidal deep brain stimulation for the treatment of patients with dystonia-choreoathetosis cerebral palsy: a prospective pilot study.", "Bilateral pallidal deep brain stimulation (BP-DBS) of the globus pallidus internus (GPi) is an effective treatment for primary dystonia, but the effect of this reversible surgical procedure on dystonia-choreoathetosis CP, which is a subtype of secondary dystonia, is unknown. ", "INTERPRETATION: Bilateral pallidal neurostimulation could be an effective treatment option for patients with dystonia-choreoathetosis CP. ", "Pallidal deep-brain stimulation in primary generalized or segmental dystonia.", "BACKGROUND: Neurostimulation of the internal globus pallidus has been shown to be effective in reducing symptoms of primary dystonia. ", "CONCLUSIONS: Bilateral pallidal neurostimulation for 3 months was more effective than sham stimulation in patients with primary generalized or segmental dystonia.", "OBJECTIVE: To assess the effects of bilateral pallidal deep brain stimulation (DBS) on mood and cognitive performance in patients with dystonia before surgery (at baseline, while patients received their usual treatment) and 12 months postoperatively (while patients received neurostimulation and their medications) in a multicenter prospective study. ", "CONCLUSIONS: Bilateral pallidal stimulation has a good benefit-to-risk ratio as it did not negatively affect cognitive performance and mood in primary dystonia, while a significant motor improvement was obtained.", "Despite that deep brain stimulation (DBS) of the globus pallidus internus (GPi) is emerging as the favored intervention for patients with medically intractable dystonia, the pathophysiological mechanisms of dystonia are largely unclear. In eight patients with primary dystonia who were treated with bilateral chronic pallidal stimulation, we correlated symptom-related electromyogram (EMG) activity of the most affected muscles with the local field potentials (LFPs) recorded from the globus pallidus electrodes. ", "Bilateral deep-brain stimulation of the globus pallidus in primary generalized dystonia.", "METHODS: We performed a prospective, controlled, multicenter study assessing the efficacy and safety of bilateral pallidal stimulation in 22 patients with primary generalized dystonia. ", "CONCLUSIONS: These findings support the efficacy and safety of the use of bilateral stimulation of the internal globus pallidus in selected patients with primary generalized dystonia.", "Bilateral pallidotomy or pallidal stimulation may provide major benefit especially in patients with generalized, disabling dystonia with the most dramatic improvements in dystonia type 1 patients.", "This suggests that neurostimulation of the VIM may be an effective treatment for myoclonus in pharmacologically intractable IMDS.", "We report on the effects of bilateral neurostimulation of the ventral intermediate thalamic nucleus (VIM) in a patient with medically intractable and progressing inherited myoclonus dystonia syndrome (IMDS). ", "Neurostimulation of the ventral intermediate thalamic nucleus in inherited myoclonus-dystonia syndrome.", "Pallidal and thalamic neurostimulation in severe tardive dystonia.", "After informed consent, a bilateral stereotactic electrode placement targeting the ventral intermediate thalamic nucleus (VIM) and the globus pallidus internus (GPi) was performed.", "Stimulation of the VIM did not improve the hyperkinetic movements and simultaneous stimulation of both the GPi and the VIM did not result in any additional benefit. ", "Bilateral pallidal neurostimulation could be an effective treatment option for patients with dystonia-choreoathetosis CP.", "3 years and 5 years after surgery, pallidal neurostimulation continues to be an effective and relatively safe treatment option for patients with severe idiopathic dystonia.", " This long-term observation provides further evidence in favour of pallidal neurostimulation as a first-line treatment for patients with medically intractable, segmental, or generalised dystonia.", "INTERPRETATION: 3 years and 5 years after surgery, pallidal neurostimulation continues to be an effective and relatively safe treatment option for patients with severe idiopathic dystonia.", "This long-term observation provides further evidence in favour of pallidal neurostimulation as a first-line treatment for patients with medically intractable, segmental, or generalised dystonia.", "Bilateral pallidal neurostimulation could be an effective treatment option for patients with dystonia-choreoathetosis CP", "3 years and 5 years after surgery, pallidal neurostimulation continues to be an effective and relatively safe treatment option for patients with severe idiopathic dystonia" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/17093249", "http://www.ncbi.nlm.nih.gov/pubmed/11254790", "http://www.ncbi.nlm.nih.gov/pubmed/11481711", "http://www.ncbi.nlm.nih.gov/pubmed/21549607", "http://www.ncbi.nlm.nih.gov/pubmed/12151848", "http://www.ncbi.nlm.nih.gov/pubmed/24268100", "http://www.ncbi.nlm.nih.gov/pubmed/16410002", "http://www.ncbi.nlm.nih.gov/pubmed/24292857", "http://www.ncbi.nlm.nih.gov/pubmed/15689584", "http://www.ncbi.nlm.nih.gov/pubmed/17277672", "http://www.ncbi.nlm.nih.gov/pubmed/23123071", "http://www.ncbi.nlm.nih.gov/pubmed/19576854", "http://www.ncbi.nlm.nih.gov/pubmed/25127231", "http://www.ncbi.nlm.nih.gov/pubmed/23037556", "http://www.ncbi.nlm.nih.gov/pubmed/16717218", "http://www.ncbi.nlm.nih.gov/pubmed/20482602", "http://www.ncbi.nlm.nih.gov/pubmed/17973330" ]

[]

[ "http://www.disease-ontology.org/api/metadata/DOID:543" ]

[ "The hair cell is located in the inner ear, a tissue that is particularly reliant on actin-rich structures and unconventional myosin isozymes. Within the pericuticular necklace, a domain of the hair cell, certain unconventional myosin isozymes are located, namely myosins-Ibeta, myosin-VI, and myosin-VIIa." ]

[ "myosins-Ibeta", "myosin-VI", "myosin-VIIa" ]

[ "Myosin 1 beta, VI, VIIa and probably XV are all expressed within a single cell in the inner ear, the hair cell.", "The myosin isozymes expressed in the hair cell all have unique domains of expression and in some areas, such as the pericuticular necklace, several domains overlap.", "Substantial amounts of myosins-Ibeta, -VI, and -VIIa are located in a pericuticular necklace", "four unconventional myosin isozymes in the inner ear, a tissue that is particularly reliant on actin-rich structures and unconventional myosin isozymes.", "The myosin isozymes expressed in the hair cell all have unique domains of expression and in some areas, such as the pericuticular necklace, several domains overlap.", "Substantial amounts of myosins-Ibeta, -VI, and -VIIa are located in a pericuticular necklace that is largely free of F-actin, squeezed between (but not associated with) actin of the cuticular plate and the circumferential belt.", "To understand how cells differentially use the dozens of myosin isozymes present in each genome, we examined the distribution of four unconventional myosin isozymes in the inner ear, a tissue that is particularly reliant on actin-rich structures and unconventional myosin isozymes.", "This study examined the changes of myosin VI and myosin VIIa, two unconventional myosins that are critical for normal hair cell formation and function, during hair cell death and regeneration.", "Substantial amounts of myosins-Ibeta, -VI, and -VIIa are located in a pericuticular necklace that is largely free of F-actin, squeezed between (but not associated with) actin of the cuticular plate and the circumferential belt.", "Substantial amounts of myosins-Ibeta, -VI, and -VIIa are located in a pericuticular necklace that is largely free of F-actin, squeezed between (but not associated with) actin of the cuticular plate and the circumferential belt", "The myosin isozymes expressed in the hair cell all have unique domains of expression and in some areas, such as the pericuticular necklace, several domains overlap", "To understand how cells differentially use the dozens of myosin isozymes present in each genome, we examined the distribution of four unconventional myosin isozymes in the inner ear, a tissue that is particularly reliant on actin-rich structures and unconventional myosin isozymes" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/12471897", "http://www.ncbi.nlm.nih.gov/pubmed/12486594", "http://www.ncbi.nlm.nih.gov/pubmed/17048225", "http://www.ncbi.nlm.nih.gov/pubmed/9182663" ]

[]

[ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0035315", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0002093", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0032507" ]

[ "The novel treatment strategy proposed for treatment of Spinocerebellar ataxia type 3 is the removal of the toxic polyglutamine repeat from the ataxin-3 protein through antisense oligonucleotide-mediated exon skipping while maintaining important wild type functions of the protein." ]

[]

[ "Ataxin-3 protein modification as a treatment strategy for spinocerebellar ataxia type 3: removal of the CAG containing exon", "Spinocerebellar ataxia type 3 is caused by a polyglutamine expansion in the ataxin-3 protein, resulting in gain of toxic function of the mutant protein. The expanded glutamine stretch in the protein is the result of a CAG triplet repeat expansion in the penultimate exon of the ATXN3 gene", "we propose a novel protein modification approach to reduce mutant ataxin-3 toxicity by removing the toxic polyglutamine repeat from the ataxin-3 protein through antisense oligonucleotide-mediated exon skipping while maintaining important wild type functions of the protein", "exon skipping may be a novel therapeutic approach to reduce polyglutamine-induced toxicity in spinocerebellar ataxia type 3", "Ataxin-3 protein modification as a treatment strategy for spinocerebellar ataxia type 3: removal of the CAG containing exon.", "Ataxin-3 protein modification as a treatment strategy for spinocerebellar ataxia type 3: removal of the CAG containing exon." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/23659897" ]

[]

[]

[ "Angiogenin binds to CT repeats that are abundant in the nontranscribed region of the ribosomal RNA gene. An angiogenin-binding DNA sequence (CTCTCTCTCTCTCTCTCCCTC) has been identified and designated angiogenin-binding element (ABE)." ]

[]

[ "ANG binds at the upstream control element (UCE) of the promoter and enhances promoter occupancy of RNA Pol I as well as the selectivity factor SL1 components TAFI 48 and TAFI 110. ", " Here we report that angiogenin binds to CT repeats that are abundant in the nontranscribed region of the ribosomal RNA gene. An angiogenin-binding DNA sequence (CTCTCTCTCTCTCTCTCCCTC) has been identified and designated angiogenin-binding element (ABE). " ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/24122807", "http://www.ncbi.nlm.nih.gov/pubmed/7875314", "http://www.ncbi.nlm.nih.gov/pubmed/12515546", "http://www.ncbi.nlm.nih.gov/pubmed/9413551", "http://www.ncbi.nlm.nih.gov/pubmed/2813401", "http://www.ncbi.nlm.nih.gov/pubmed/3289612" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004602", "http://www.uniprot.org/uniprot/ANGI_GORGO", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0032311" ]

[ "In unstimulated cells, NF-kB transcription factors are retained in the cytoplasm with the inhibitory activity of I-kBs, Sef, NF-kB1 (p105) and NF-kB2 (p100)." ]

[ "I-kBs", "Sef", "NF-kB1 (p105)", "NF-kB2 (p100)" ]

[ "Sef is an inhibitor of proinflammatory cytokine signaling, acting by cytoplasmic sequestration of NF-κB", "According to the classical model, NF-κB is retained in the cytoplasm of resting cells via binding to inhibitory, IκB proteins and translocates into the nucleus upon their ligand-induced degradation.", "Like IκBs, Sef sequesters NF-κB in the cytoplasm of resting cells.", "The activity of NF-κB is tightly controlled through its cytoplasmic sequestration by specific inhibitors, IκBs.", "The inhibitor of NF-kappaB (IkappaB) family of proteins is believed to regulate NF-kappaB activity by cytoplasmic sequestration.", "IkappaBalpha is an inhibitory molecule that sequesters NF-kappaB dimers in the cytoplasm of unstimulated cells.", "p105.Ikappa Bgamma and prototypical Ikappa Bs use a similar mechanism to bind but a different mechanism to regulate the subcellular localization of NF-kappa B", "We show that the death domain of p105 (also of IkappaBgamma) is essential for the cytoplasmic sequestration of NF-kappaB by p105 and IkappaBgamma.", "In unstimulated cells, NF-kappaB transcription factors are retained in the cytoplasm by inhibitory IkappaB proteins.", "The ability of the IkappaB alpha protein to sequester dimeric NF-kappaB/Rel proteins in the cytoplasm provides an effective mechanism for regulating the potent transcriptional activation properties of NF-kappaB/Rel family members.", "The presence of a discrete nuclear import sequence in IkappaB alpha suggests that cytoplasmic sequestration of the NF-kappaB/Rel-IkappaB alpha complex is a consequence of the mutual masking of the NLS within NF-kappaB/Rel proteins and the import sequence within IkappaB alpha.", "The viral Tax protein, which is encoded by human T-cell leukaemia virus HTLV-I, activates nuclear translocation of the NF-kappa B/Rel transcription factors and relieves cytoplasmic sequestration of RelA and Rel by heterodimerization with NF-kappa B1/p1O5 (refs 1,2).", "The I-kappa B protein, which is necessary for the cytoplasmic sequestration of the NF-kappa B transcription factor complex, was identified specifically in regions of limbic, hypothalamic, and autonomic nuclei.", "Human T-cell leukemia virus type I Tax-protein-mediated activation of NF-kappa B from p100 (NF-kappa B2)-inhibited cytoplasmic reservoirs", "The preexisting NF-kappa B proteins are retained in the cytoplasm of cells by association with inhibitory ankyrin-motif-containing I kappa B proteins, primarily I kappa B-alpha but also including the precursor proteins p105 (NF-kappa B1) and p100 (NF-kappa B2)." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/22975329", "http://www.ncbi.nlm.nih.gov/pubmed/16136188", "http://www.ncbi.nlm.nih.gov/pubmed/12399470", "http://www.ncbi.nlm.nih.gov/pubmed/12972430", "http://www.ncbi.nlm.nih.gov/pubmed/20845110", "http://www.ncbi.nlm.nih.gov/pubmed/8692272", "http://www.ncbi.nlm.nih.gov/pubmed/10454561", "http://www.ncbi.nlm.nih.gov/pubmed/8804077", "http://www.ncbi.nlm.nih.gov/pubmed/9566872", "http://www.ncbi.nlm.nih.gov/pubmed/7809091" ]

[]

[ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0008588", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0035525", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0032088", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0042994", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0007253", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0051220", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016328", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0071159", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0042347" ]

[ "Yes, SDHAF2 or hSDH5, is the gene encoding the enzyme responsible for the flavination of SDHA.", "Yes, SDHAF2 is required for flavination of SDHA." ]

[ "yes" ]

[ "the gene encoding the enzyme responsible for the flavination of SDHA (SDHAF2 or hSDH5)", "SDHAF2, required for flavination of SDHA", "Pheochromocytoma-paraganglioma syndrome is caused by mutations in SDHB, SDHC, and SDHD, encoding subunits of succinate dehydrogenase (SDH), and in SDHAF2, required for flavination of SDHA. ", "At present, these are RET proto-oncogene, von Hippel-Lindau disease tumor suppressor gene (VHL), neurofibromatosis type 1 tumor suppressor gene (NF1), genes encoding the succinate dehydrogenase (SDH) complex subunits SDHB, SDHC, and SDHD, but also SDHA, the gene encoding the enzyme responsible for the flavination of SDHA (SDHAF2 or hSDH5), and the newly described TMEM127 and MAX tumor suppressor genes.", "Pheochromocytoma-paraganglioma syndrome is caused by mutations in SDHB, SDHC, and SDHD, encoding subunits of succinate dehydrogenase (SDH), and in SDHAF2, required for flavination of SDHA.", "In a recent issue of Science, Rutter and coworkers showed that SDH5 is required for the flavination of SDHA, which is necessary for SDH assembly and function.", "At present, these are RET proto-oncogene, von Hippel-Lindau disease tumor suppressor gene (VHL), neurofibromatosis type 1 tumor suppressor gene (NF1), genes encoding the succinate dehydrogenase (SDH) complex subunits SDHB, SDHC, and SDHD, but also SDHA, the gene encoding the enzyme responsible for the flavination of SDHA (SDHAF2 or hSDH5), and the newly described TMEM127 and MAX tumor suppressor genes", "Pheochromocytoma-paraganglioma syndrome is caused by mutations in SDHB, SDHC, and SDHD, encoding subunits of succinate dehydrogenase (SDH), and in SDHAF2, required for flavination of SDHA", "CONTEXT: Pheochromocytoma-paraganglioma syndrome is caused by mutations in SDHB, SDHC, and SDHD, encoding subunits of succinate dehydrogenase (SDH), and in SDHAF2, required for flavination of SDHA. ", "This gene is co-expressed with a number of genes encoding mitochondrial proteins, including SDH1-1, and has low partial sequence similarity to human SDHAF2, a protein required for flavin-adenine dinucleotide (FAD) insertion into SDH. " ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/21752896", "http://www.ncbi.nlm.nih.gov/pubmed/23036115", "http://www.ncbi.nlm.nih.gov/pubmed/19732718", "http://www.ncbi.nlm.nih.gov/pubmed/23061808" ]

[]

[]

[ "Marchesani syndrome is transmitted either by an autosomal dominant (mutations in FBN1) or an autosomal recessive (mutations in ADAMTS10) mode of inheritance" ]

[ "autosomal dominant or autosomal recessive" ]

[ "Autosomal recessive and autosomal dominant WMS cannot be distinguished by clinical findings alone. ", "Weill-Marchesani syndrome (WMS) is a well-characterized disorder in which patients develop eye and skeletal abnormalities. Autosomal-recessive and autosomal-dominant forms of WMS are caused by mutations in ADAMTS10 and FBN1 genes, respectively. ", "Finally, WMS is transmitted either by an autosomal dominant or an autosomal recessive (AR) mode of inheritance, GD by an autosomal recessive mode of inheritance and AD by an autosomal dominant mode of inheritance. ", "Weill-Marchesani syndrome (WMS) is a rare condition characterized by short stature, brachydactyly, joint stiffness, and characteristic eye abnormalities including microspherophakia, ectopia of lens, severe myopia, and glaucoma. Both autosomal recessive (AR) and autosomal dominant (AD) modes of inheritance have been described for WMS.", "Weill-Marchesani syndrome (WMS) is a connective tissue disorder characterised by short stature, brachydactyly, joint stiffness, and characteristic eye anomalies including microspherophakia, ectopia of the lenses, severe myopia, and glaucoma. Both autosomal recessive (AR) and autosomal dominant (AD) modes of inheritance have been described and a gene for AR WMS has recently been mapped to chromosome 19p13.3-p13.2.", "Both autosomal recessive and autosomal dominant modes of inheritance have been described in association with WMS. ", "We report 6 patients with Weill-Marchesani syndrome (with or without ocular involvement) in three generations, identified by screening 26 members of two families. This is the largest family in the literature showing an autosomal dominant pattern of inheritance.", "Weill-Marchesani syndrome comprises short stature, brachydactyly, microspherophakia, glaucoma, and ectopia lentis is regarded as an autosomal recessive trait", "We present two families each with affected individuals in 3 generations demonstrating autosomal dominant inheritance of Weill-Marchesani syndrome.", "Weill-Marchesani syndrome is a rare, generalized disorder of connective tissue manifested by short stature, brachymorphia, and spherophakia. Inheritance is autosomal recessive." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/10707143", "http://www.ncbi.nlm.nih.gov/pubmed/8914744", "http://www.ncbi.nlm.nih.gov/pubmed/20301293", "http://www.ncbi.nlm.nih.gov/pubmed/19396027", "http://www.ncbi.nlm.nih.gov/pubmed/6739588", "http://www.ncbi.nlm.nih.gov/pubmed/19836009", "http://www.ncbi.nlm.nih.gov/pubmed/12525539", "http://www.ncbi.nlm.nih.gov/pubmed/14598350", "http://www.ncbi.nlm.nih.gov/pubmed/11941487" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D056846", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D040582" ]

[ "Clinical trials have shown that Tumor-treating fields are effective for treatment of non-small cell lung cancer and glioblastoma. Ongoing and future trials will evaluate TTFields in solid tumor brain metastases, and ovarian, pancreatic cancers and multidrug resistance cancer cells." ]

[ "non-small cell lung cancer", "glioblastoma" ]

[ "Alternating electric fields (tumor-treating fields therapy) can improve chemotherapy treatment efficacy in non-small cell lung cancer both in vitro and in vivo.", "e evaluated the effects of combining TTFields with standard chemotherapeutic agents on several NSCLC cell lines, both in vitro and in vivo. Frequency titration curves demonstrated that the inhibitory effects of TTFields were maximal at 150 kHz for all NSCLC cell lines tested, and that the addition of TTFields to chemotherapy resulted in enhanced treatment efficacy across all cell lines. ", "Together, these findings suggest that combining TTFields therapy with chemotherapy may provide an additive efficacy benefit in the management of NSCLC.", "Response patterns of recurrent glioblastomas treated with tumor-treating fields.", "NovoTTF Therapy is a novel and US Food and Drug Administration (FDA)-approved antimitotic treatment for recurrent GBM with potential benefits compared with other options. Recurrent GBM patients from two prior trials with demonstrated radiologic tumor response to single-agent NovoTTF Therapy were analyzed to better characterize tumor response patterns and evaluate the associations between response, compliance, and OS. In addition, a compartmental tumor growth model was developed and evaluated for its ability to predict GBM response to tumor-treating fields (TTFields). The overall response rate across both trials was 15% (4% complete responses): 14% in the phase III trial (14/120) and 20% (2/10) in a pilot study. Tumor responses to NovoTTF Therapy developed slowly (median time to response, 5.2 months) but were durable (median duration, 12.9 months).", "NovoTTF Therapy is a novel antimitotic treatment for recurrent GBM associated with slowly developing but durable tumor responses in approximately 15% of patients.", "The effect of field strength on glioblastoma multiforme response in patients treated with the NovoTTF™-100A system.", " An ongoing trial is assessing its efficacy for newly diagnosed glioblastoma multiforme (GBM) and it has been FDA-approved for recurrent GBM.", "We present three patients with GBM in whom the fields were adjusted at recurrence and the effects of each adjustment.", "The first patient underwent subtotal resection, radiotherapy with temozolomide (TMZ), and then began NovoTTF Therapy with metronomic TMZ. ", " A second patient underwent two resections followed by radiotherapy/TMZ and NovoTTF Therapy/TMZ. Six months later, two new distal lesions were noted, and he underwent further resection with adjustment of his fields. He remained stable over the subsequent year on NovoTTF Therapy and bevacizumab. A third patient on NovoTTF Therapy/TMZ remained stable for two years but developed a small, slow growing enhancing lesion, which was resected, and his fields were adjusted accordingly. ", "A phase I/II trial of Tumor Treating Fields (TTFields) therapy in combination with pemetrexed for advanced non-small cell lung cancer.", "Promising preclinical data have led to a single arm phase I/II trial in NSCLC patients.METHODS: Forty-two inoperable stage IIIB (with pleural effusion) and IV NSCLC patients who had had tumor progression received pemetrexed 500 mg/m(2) iv q3w together with daily TTFields therapy until disease progression.", "The median time to in-field progression was 28 weeks and the median time to systemic progression was 22 weeks.", "CONCLUSIONS: The combination of TTFields and pemetrexed as a second line therapy for NSCLC is safe and potentially more effective than pemetrexed alone. TTFields improved disease control within the treatment field and a phase III study is planned to further investigate its role as a novel treatment in NSCLC.", "Tumor treating fields (TTFields) is a noninvasive, regional antimitotic treatment modality that has been approved for the treatment of recurrent glioblastoma by the U.S. FDA and has a CE mark in Europe. ", "The antimitotic effect of TTFields therapy has been demonstrated in multiple cell lines when the appropriate frequency was utilized. A phase III trial of TTFields monotherapy compared to active chemotherapy in recurrent glioblastoma patients established that TTFields therapy is associated with minimal toxicity, better quality of life, and comparable efficacy to chemotherapy. Ongoing and future trials will evaluate TTFields in newly diagnosed glioblastoma, solid tumor brain metastases, nonsmall cell lung cancer, and ovarian and pancreatic cancers.", "The U.S. Food and Drug Administration has approved the first device, the NovoTTF-100A™, that uses this technology and is indicated for use in progressive glioblastoma multiforme after standard therapies have failed. Promising clinical trial results will likely lead to expanded uses in primary brain tumors and other cancer types. ", "Long-term survival of patients suffering from glioblastoma multiforme treated with tumor-treating fields.", "Tumor-treating fields (TTField) therapy is a novel treatment technique that has recently received CE and FDA approval for the treatment of RGBM, and is based on the principle that low intensity, intermediate frequency electric fields (100 to 300 kHz) may induce apoptosis in specific cell types. Our center was the first to apply TTField treatment to histologically proven GBM in a small pilot study of 20 individuals in 2004 and 2005, and four of those original 20 patients are still alive today. We report two cases of GBM and two cases of RGBM treated by TTField therapy, all in good health and no longer receiving any treatment more than seven years after initiating TTField therapy, with no clinical or radiological evidence of recurrence.", "Tumor treating fields (TTFields) are low intensity (1 ? 2 V/cm), intermediate frequency (100 ? 200 kHz) alternating electric fields administered using insulated electrodes placed on the skin surrounding the region of a malignant tumor. ", "Furthermore, it summarizes the clinical experience with TTFields, mainly in two indications: one in recurrent glioblastoma multiforme: in a large prospective randomized Phase III trial TTFields was compared with best standard care (including chemotherapy): TTFields significantly improved median overall survival (OS) compared with standard therapy (7.8 vs 6.1 months) for the patients treated per protocol.", "The second indication was a Phase II study in second-line non-small cell lung cancer, where TTFields was administered concomitantly with pemetrexed. ", "EXPERT OPINION: The proof of concept of TTFields has been well demonstrated in the preclinical setting, and the clinical data seem promising in various tumor types. ", "CONCLUSIONS: The results indicate that TTFields alone and in combination with paclitaxel and doxorubicin effectively reduce the viability of both wild type and MDR cell sub-lines and thus can potentially be used as an effective treatment of drug resistant tumors.", "Alternating electric fields (TTFields) inhibit metastatic spread of solid tumors to the lungs.", "Tumor treating fields (TTFields) are low intensity, intermediate frequency, alternating electric fields used to treat cancerous tumors. This novel treatment modality effectively inhibits the growth of solid tumors in vivo and has shown promise in pilot clinical trials in patients with advanced stage solid tumors.", "BACKGROUND: The present study explores the efficacy and toxicity of combining a new, non-toxic, cancer treatment modality, termed Tumor Treating Fields (TTFields), with chemotherapeutic treatment in-vitro, in-vivo and in a pilot clinical trial.", "In addition, we studied the effects of combining chemotherapy with TTFields in an animal tumor model and in a pilot clinical trial in recurrent and newly diagnosed GBM patients.RESULTS: The efficacy of TTFields-chemotherapy combination in-vitro was found to be additive with a tendency towards synergism for all drugs and cell lines tested (combination index", "A pilot study with very low-intensity, intermediate-frequency electric fields in patients with locally advanced and/or metastatic solid tumors.", "PATIENTS AND METHODS: This open, prospective pilot study was designed to evaluate the safety, tolerability, and efficacy profile of TTFields treatment in patients with locally advanced and/or metastatic solid tumors using the NovoTTF100A(TM) device.", "Outcomes showed 1 partial response of a treated skin metastasis from a primary breast cancer, 3 cases where tumor growth was arrested during treatment, and 1 case of disease progression. One mesothelioma patient experienced lesion regression near TTFields with simultaneous tumor stability or progression in distal areas.CONCLUSION: Although the number of patients in this study is small, the lack of therapy toxicity and the efficacy observed in data gathered to date indicate the potential of TTFields as a new treatment modality for solid tumors, definitely warranting further investigation.", "Mitotic disruption and reduced clonogenicity of pancreatic cancer cells in vitro and in vivo by tumor treating fields.", "OBJECTIVES: Tumor Treating Fields (TTFields) are a non-invasive cancer treatment modality approved for the treatment of patients with recurrent glioblastoma. The present study determined the efficacy and mechanism of action of TTFields in preclinical models of pancreatic cancer.", "RESULTS: Application of TTFields in vitro showed a significant decrease in cell count, an increase in cell volume and reduced clonogenicity. Further analysis demonstrated significant increase in the number of abnormal mitotic figures, as well as a decrease in G2-M cell population. In hamsters with orthotopic pancreatic tumors, TTFields significantly reduced tumor volume accompanied by an increase in the frequency of abnormal mitotic events. TTFields efficacy was enhanced both in vitro and in vivo when combined with chemotherapy.CONCLUSIONS: These results provide the first evidence that TTFields serve as an effective antimitotic treatment in preclinical pancreatic cancer models and have a long term negative effect on cancer cell survival. These results make TTFields an attractive candidate for testing in the treatment of patients with pancreatic cancer.", "Tumor Treating Fields (TTFields) are a non-invasive cancer treatment modality approved for the treatment of patients with recurrent glioblastoma.", "In addition, a compartmental tumor growth model was developed and evaluated for its ability to predict GBM response to tumor-treating fields (TTFields).", "Tumor-treating fields (TTField) therapy is a novel treatment technique that has recently received CE and FDA approval for the treatment of RGBM, and is based on the principle that low intensity, intermediate frequency electric fields (100 to 300 kHz) may induce apoptosis in specific cell types.", "Tumor treating fields (TTFields) is a noninvasive, regional antimitotic treatment modality that has been approved for the treatment of recurrent glioblastoma by the U.S. FDA and has a CE mark in Europe.", "Tumor-treating fields (TTField) therapy is a novel treatment technique that has recently received CE and FDA approval for the treatment of RGBM, and is based on the principle that low intensity, intermediate frequency electric fields (100 to 300 kHz) may induce apoptosis in specific cell types. ", "In addition, a compartmental tumor growth model was developed and evaluated for its ability to predict GBM response to tumor-treating fields (TTFields). ", "OBJECTIVES: Tumor Treating Fields (TTFields) are a non-invasive cancer treatment modality approved for the treatment of patients with recurrent glioblastoma. ", "Tumor Treating Fields (TTFields) are a non-invasive cancer treatment modality approved for the treatment of patients with recurrent glioblastoma." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/19133110", "http://www.ncbi.nlm.nih.gov/pubmed/23899985", "http://www.ncbi.nlm.nih.gov/pubmed/23095807", "http://www.ncbi.nlm.nih.gov/pubmed/18596382", "http://www.ncbi.nlm.nih.gov/pubmed/24884522", "http://www.ncbi.nlm.nih.gov/pubmed/21548832", "http://www.ncbi.nlm.nih.gov/pubmed/24555979", "http://www.ncbi.nlm.nih.gov/pubmed/20492723", "http://www.ncbi.nlm.nih.gov/pubmed/25213867", "http://www.ncbi.nlm.nih.gov/pubmed/23659608", "http://www.ncbi.nlm.nih.gov/pubmed/23891283", "http://www.ncbi.nlm.nih.gov/pubmed/25213870", "http://www.ncbi.nlm.nih.gov/pubmed/19387848" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009369", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013812" ]

[ "Using acetyl-specific K516 antibodies, we show that acetylation of endogenous S6K1 at this site is potently induced upon growth factor stimulation. We propose that K516 acetylation may serve to modulate important kinase-independent functions of S6K1 in response to growth factor signalling. Following mitogen stimulation, S6Ks interact with the p300 and p300/CBP-associated factor (PCAF) acetyltransferases. S6Ks can be acetylated by p300 and PCAF in vitro and S6K acetylation is detected in cells expressing p300", "Acetylation of S6K1 and 2 is increased upon the inhibition of class I/II histone deacetylases (HDACs) by trichostatin-A, while the enhancement of S6K1 acetylation by nicotinamide suggests the additional involvement of sirtuin deacetylases in S6K deacetylationUsing acetyl-specific K516 antibodies, we show that acetylation of endogenous S6K1 at this site is potently induced upon growth factor stimulation", "Using acetyl-specific K516 antibodies, we show that acetylation of endogenous S6K1 at this site is potently induced upon growth factor stimulation We propose that K516 acetylation may serve to modulate important kinase-independent functions of S6K1 in response to growth factor signalling", "K516 acetylation may serve to modulate important kinase-independent functions of S6K1 in response to growth factor signalling, followed by interaction with the p300 and p300/CBP-associated factor (PCAF) acetyltransferases. S6K1 can be acetylated by p300 and PCAF in vitro and S6K acetylation is detected in cells expressing p300." ]

[]

[ "S6K1 is acetylated at lysine 516 in response to growth factor stimulation", "In addition to phosphorylation, we have recently shown that S6K1 is also targeted by lysine acetylation", "Here, using tandem mass spectrometry we have mapped acetylation of S6K1 to lysine 516, a site close to the C-terminus of the kinase that is highly conserved amongst vertebrate S6K1 orthologues", "Using acetyl-specific K516 antibodies, we show that acetylation of endogenous S6K1 at this site is potently induced upon growth factor stimulation", "We propose that K516 acetylation may serve to modulate important kinase-independent functions of S6K1 in response to growth factor signalling", "Histone acetyltransferases interact with and acetylate p70 ribosomal S6 kinases in vitro and in vivo", "Following mitogen stimulation, S6Ks interact with the p300 and p300/CBP-associated factor (PCAF) acetyltransferases. S6Ks can be acetylated by p300 and PCAF in vitro and S6K acetylation is detected in cells expressing p300", "Acetylation of S6K1 and 2 is increased upon the inhibition of class I/II histone deacetylases (HDACs) by trichostatin-A, while the enhancement of S6K1 acetylation by nicotinamide suggests the additional involvement of sirtuin deacetylases in S6K deacetylation", "Following mitogen stimulation, S6Ks interact with the p300 and p300/CBP-associated factor (PCAF) acetyltransferases. S6Ks can be acetylated by p300 and PCAF in vitro and S6K acetylation is detected in cells expressing p300.", "Furthermore, it appears that the acetylation sites targeted by p300 lie within the divergent C-terminal regulatory domains of both S6K1 and S6K2.", "Furthermore, it appears that the acetylation sites targeted by p300 lie within the divergent C-terminal regulatory domains of both S6K1 and S6K2", "We propose that K516 acetylation may serve to modulate important kinase-independent functions of S6K1 in response to growth factor signalling." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/20599721", "http://www.ncbi.nlm.nih.gov/pubmed/19961954" ]

[]

[ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0006473", "http://www.uniprot.org/uniprot/KS6B1_MOUSE", "http://www.uniprot.org/uniprot/KS6B1_BOVIN", "http://www.uniprot.org/uniprot/KS6B1_RAT", "http://www.uniprot.org/uniprot/KS6B1_HUMAN", "http://www.uniprot.org/uniprot/KS6B1_RABIT" ]

[ "Angiocrine factors are: Ccl4, neurotensin, vascular endothelial growth factor, metalloproteinases-1, thrombospondin 3, Slit2, hepatocyte growth factor, Wnt2. " ]

[ "Ccl4", "neurotensin", "vascular endothelial growth factor", "metalloproteinases-1", "thrombospondin 3", "Slit2", "hepatocyte growth factor", "Wnt2" ]

[ "Ccl4 and neurotensin (Nts) (angiocrine factors)", "vascular endothelial growth factor (VEGF)-A was identified as the most abundantly expressed factor, ", "angiocrine factors tissue inhibitor of metalloproteinases-1 (Timp-1) and thrombospondin 3 (THBS3) ", "We found that Slit2, which is negatively regulated by endothelial EphA2 receptor, is one such tumor suppressive angiocrine factor. ", "angiocrine factors, including hepatocyte growth factor (HGF) and Wnt2." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/21148069", "http://www.ncbi.nlm.nih.gov/pubmed/24018375", "http://www.ncbi.nlm.nih.gov/pubmed/24257808", "http://www.ncbi.nlm.nih.gov/pubmed/20094048", "http://www.ncbi.nlm.nih.gov/pubmed/21068842", "http://www.ncbi.nlm.nih.gov/pubmed/24257019" ]

[]

[]

[ "Protein carbamylation is a post-translational modification that can occur in the presence of urea. In solution, urea is in equilibrium with ammonium cyanate, and carbamylation occurs when cyanate ions react with the amino groups of lysines, arginines, protein N-termini, as well as sulfhydryl groups of cysteines. Protein carbamylation is one of the important post-translational modifications, which plays a pivotal role in a number of biological conditions, such as diseases, chronic renal failure and atherosclerosis." ]

[]

[ "urea solution can cause carbamylation at the N termini of proteins/peptides and at the side chain amino groups of lysine and arginine residues. ", "Carbamylation describes a nonenzymatic posttranslational protein modification mediated by cyanate, a dissociation product of urea. ", "Cyanate, a reactive electrophilic species in equilibrium with urea, posttranslationally modifies proteins through a process called carbamylation, which promotes atherosclerosis. ", "Protein carbamylation, a posttranslational modification promoted during uremia and catalyzed by myeloperoxidase (MPO) at sites of inflammation, is linked to altered protein structure, vascular dysfunction, and poor prognosis. ", "Carbamylation (carbamoylation) of lysine residues and protein N-termini is a nonenzymatic PTM that has been related to protein ageing. In contrast to other PTM, such as phosphorylation, carbamylation can be artificially introduced during sample preparation with urea, thus affecting studies directed toward in vivo carbamylation. ", "Carbamylation is a general process involved in protein molecular ageing due to the nonenzymatic binding of isocyanic acid, mainly generated by urea dissociation, to free amino groups. ", "Protein carbamylation is one of the important post-translational modifications, which plays a pivotal role in a number of biological conditions, such as diseases, chronic renal failure and atherosclerosis.", "Protein carbamylation is a post-translational modification that can occur in the presence of urea. In solution, urea is in equilibrium with ammonium cyanate, and carbamylation occurs when cyanate ions react with the amino groups of lysines, arginines, protein N-termini, as well as sulfhydryl groups of cysteines. ", "Carbamylation of proteins through reactive cyanate has been demonstrated to predict an increased cardiovascular risk. ", "Protein carbamylation is of great concern both in vivo and in vitro. Here, we report the first structural characterization of a protein carbamylated at the N-terminal proline. ", "Post-translational modification and functional impairment of proteins through carbamylation is thought to promote vascular dysfunction during end-stage renal disease. Cyanate, a reactive species in equilibrium with urea, carbamylates protein lysine residues to form epsilon-carbamyllysine (homocitrulline), altering protein structure and function." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/23335428", "http://www.ncbi.nlm.nih.gov/pubmed/24161613", "http://www.ncbi.nlm.nih.gov/pubmed/21235354", "http://www.ncbi.nlm.nih.gov/pubmed/25037561", "http://www.ncbi.nlm.nih.gov/pubmed/24056952", "http://www.ncbi.nlm.nih.gov/pubmed/24386107", "http://www.ncbi.nlm.nih.gov/pubmed/17828273", "http://www.ncbi.nlm.nih.gov/pubmed/24324801", "http://www.ncbi.nlm.nih.gov/pubmed/24900204", "http://www.ncbi.nlm.nih.gov/pubmed/21838543", "http://www.ncbi.nlm.nih.gov/pubmed/23582087", "http://www.ncbi.nlm.nih.gov/pubmed/23431074" ]

[]

[]

[ "Episodic ataxia type 6, is caused by mutations in the gene encoding a glial glutamate transporter, the excitatory amino acid transporter-1. Reduced glutamate uptake by mutant excitatory amino acid transporter-1 (EAAT1) has been thought to be the main pathophysiological process in episodic ataxia type 6." ]

[ "EAAT1 mutations" ]

[ "There are several genetically and clinically distinct forms of this disease, and one of them, episodic ataxia type 6, is caused by mutations in the gene encoding a glial glutamate transporter, the excitatory amino acid transporter-1. So far, reduced glutamate uptake by mutant excitatory amino acid transporter-1 has been thought to be the main pathophysiological process in episodic ataxia type 6. ", "Episodic ataxia type 6 represents the first human disease found to be associated with altered function of excitatory amino acid transporter anion channels and illustrates possible physiological and pathophysiological impacts of this functional mode of this class of glutamate transporters.", "There are several genetically and clinically distinct forms of this disease, and one of them, episodic ataxia type 6, is caused by mutations in the gene encoding a glial glutamate transporter, the excitatory amino acid transporter-1. So far, reduced glutamate uptake by mutant excitatory amino acid transporter-1 has been thought to be the main pathophysiological process in episodic ataxia type 6.", "There are several genetically and clinically distinct forms of this disease, and one of them, episodic ataxia type 6, is caused by mutations in the gene encoding a glial glutamate transporter, the excitatory amino acid transporter-1." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/23107647" ]

[]

[ "http://www.disease-ontology.org/api/metadata/DOID:963" ]

[ "coupling MCM2-7 to replicative polymerases is an important feature of the regulation of chromosome replication in eukaryotes, and highlight a key role for Ctf4 in this processAnd-1/Ctf4 is therefore a new replication initiation factor that brings together the MCM2-7 helicase and the DNA pol alpha-primase complex, analogous to the linker between helicase and primase or helicase and polymerase that is seen in the bacterial replication machinery", "Ctf4 coordinates the progression of helicase and DNA polymerase alpha. Mcm10 and And-1/CTF4 recruit DNA polymerase alpha to chromatin for initiation of DNA replication. And-1/Ctf4 is therefore a new replication initiation factor that brings together the MCM2-7 helicase and the DNA pol alpha-primase complex, analogous to the linker between helicase and primase or helicase and polymerase that is seen in the bacterial replication machinery." ]

[ "Coordination of the progression of helicase and DNA polymerase alpha at the eukaryotic replication fork." ]

[ "In this report, interactions between human Ctf4 (hCtf4) and the replicative helicase containing the cell division cycle 45 (Cdc45)/minichromosome maintenance 2-7 (Mcm2-7)/Go, Ichi, Nii, and San (GINS) (CMG) proteins [human CMG (hCMG) complex] were examined", "We demonstrate that the hCtf4-CMG complex contains a homodimeric hCtf4 and a monomeric hCMG complex and suggest that the homodimeric hCtf4 acts as a platform linking polymerase α to the hCMG complex", "Drosophila Ctf4 is essential for efficient DNA replication and normal cell cycle progression", "The Ctf4 protein has been shown to be a central member of the replication fork and links the replicative MCM helicase and DNA polymerase α primase", " it has been implicated as a member of a complex that promotes replication fork stability, the Fork Protection Complex (FPC), and as being important for sister chromatid cohesion", "Drosophila Ctf4 is a conserved protein that interacts with members of the GINS complex, Mcm2, and Polymerase α primase", "Ctf4 remains a central player in DNA replication", "These data indicate that Ctf4p facilitates Mcm10p to promote the DNA replication", " hCtf4 plays an essential role in DNA replication and its ability to stimulate the replicative DNA polymerases ", "Our data indicate that a complex of the GINS and Ctf4 components of the RPC is crucial to couple MCM2-7 to DNA polymerase alpha", "coupling MCM2-7 to replicative polymerases is an important feature of the regulation of chromosome replication in eukaryotes, and highlight a key role for Ctf4 in this process", "Ctf4 coordinates the progression of helicase and DNA polymerase alpha", "Mcm10 and And-1/CTF4 recruit DNA polymerase alpha to chromatin for initiation of DNA replication", "We show that And-1/Ctf4 (Chromosome transmission fidelity 4) interacts with Mcm10, which associates with MCM2-7, and with the p180 subunit of DNA pol alpha", "And-1/Ctf4 is therefore a new replication initiation factor that brings together the MCM2-7 helicase and the DNA pol alpha-primase complex, analogous to the linker between helicase and primase or helicase and polymerase that is seen in the bacterial replication machinery", "Mcm10 and And-1/CTF4 recruit DNA polymerase alpha to chromatin for initiation of DNA replication.", "Ctf4 remains a central player in DNA replication.", "Drosophila Ctf4 is essential for efficient DNA replication and normal cell cycle progression.", "Influence of the human cohesion establishment factor Ctf4/AND-1 on DNA replication.", "Ctf4/AND-1 is a highly conserved gene product required for both DNA replication and the establishment of sister chromatid cohesion.", "In this report, we examined the mechanism of action of human Ctf4 (hCtf4) in DNA replication both in vitro and in vivo.", "And-1/Ctf4 is therefore a new replication initiation factor that brings together the MCM2-7 helicase and the DNA pol alpha-primase complex, analogous to the linker between helicase and primase or helicase and polymerase that is seen in the bacterial replication machinery.", "We show that cells lacking both Ctf4 and Mrc1 experience chronic activation of the DNA damage checkpoint during chromosome replication and do not complete the cell cycle.", "Using in vivo RNAi knockdown of CTF4 in Drosophila we show that Ctf4 is required for viability, S phase progression, sister chromatid cohesion, endoreplication, and coping with replication stress.", "We show that Ctf4 function is conserved and that Drosophila can be effectively used as a model to further probe the precise function of Ctf4 as a member of the replication fork and possible roles in development.", "Chromosome transmission fidelity 4 (Ctf4) is a conserved protein required for DNA replication.", "Here we show that three proteins required for sister chromatid cohesion, Eco1, Ctf4, and Ctf18, are found at, and Ctf4 travels along chromosomes with, replication forks.", "A key role for Ctf4 in coupling the MCM2-7 helicase to DNA polymerase alpha within the eukaryotic replisome." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/11287619", "http://www.ncbi.nlm.nih.gov/pubmed/24255107", "http://www.ncbi.nlm.nih.gov/pubmed/20381454", "http://www.ncbi.nlm.nih.gov/pubmed/19805216", "http://www.ncbi.nlm.nih.gov/pubmed/17761813", "http://www.ncbi.nlm.nih.gov/pubmed/12455694", "http://www.ncbi.nlm.nih.gov/pubmed/23334284", "http://www.ncbi.nlm.nih.gov/pubmed/19430531", "http://www.ncbi.nlm.nih.gov/pubmed/19661920", "http://www.ncbi.nlm.nih.gov/pubmed/9199353", "http://www.ncbi.nlm.nih.gov/pubmed/20980819", "http://www.ncbi.nlm.nih.gov/pubmed/24805245", "http://www.ncbi.nlm.nih.gov/pubmed/1448101", "http://www.ncbi.nlm.nih.gov/pubmed/20089864", "http://www.ncbi.nlm.nih.gov/pubmed/19496828", "http://www.ncbi.nlm.nih.gov/pubmed/16962805", "http://www.ncbi.nlm.nih.gov/pubmed/19910927", "http://www.ncbi.nlm.nih.gov/pubmed/15226378", "http://www.ncbi.nlm.nih.gov/pubmed/14742710", "http://www.ncbi.nlm.nih.gov/pubmed/21470422" ]

[]

[ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0045740", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0006261", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0006260", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004261", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0006275", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0008156" ]

[ "Yes. Hot flashes are one of the most common adverse effects of Arimidex." ]

[ "yes" ]

[ "More than a third of breast cancer patients undergoing aromatase inhibitor (AI) treatment report joint pain.", "In the first 6 weeks, emergence of joint pain was associated with increase in general pain, fatigue, disturbed sleep, hot flashes, vaginal dryness, and decreased sexual activity.", "Antiestrogen therapy can cause vasomotor symptoms similar to those occurring during menopause, including hot flashes.", "The purpose of this study was to assess the feasibility and safety of acupuncture for treatment of hot flashes in Korean patients with breast cancer receiving antiestrogen therapy.", "10 patients with breast cancer who were undergoing antiestrogen therapy with tamoxifen or anastrozole and who were suffering from hot flashes.", "During treatment, severity of hot flashes was reduced by 70%-95% in all patients.", "anastrozole has been widely used in Japan as an adjuvant treatment for postmenopausal, hormone-responsive breast cancer patients.", "The aim of this study is to evaluate the rate of bone fracture and bone mineral density (BMD) during anastrozole treatment in Japanese patients.", "Musculoskeletal disorders were the most common (26.1 %), and hot flashes were the second most common adverse event (7.9 %).", "To compare the effect of therapy with anastrozole versus a combination of fulvestrant and anastrozole in women in first relapse of endocrine-responsive breast cancer.", "fulvestrant loading dose (LD) regimen followed by monthly injection plus 1 mg of anastrozole daily or to 1 mg of anastrozole daily alone.", "Incidences of prespecified adverse events (AEs) were similar. Hot flashes were more common in the experimental arm: 63 patients (24.6%) versus 35 patients (13.8%) in the standard arm (P = .0023).", "The third-generation agents (anastrozole, letrozole, and exemestane) have been shown to be more effective and safer than the selective estrogen receptor modulators tamoxifen and raloxifen.", "AIs are well tolerated and cause a lower incidence of gynecological symptoms (vaginal bleeding, discharge, and endometrial neoplasia), venous thromboembolic events, and hot flashes compared with tamoxifen.", "Mood disturbances, somnolence, anxiety, fatigue, hot flashes, and memory impairment have been reported among patients receiving anastrozole as adjuvant therapy.", "Twenty-five PM-BC patients received, in sequence, leuprorelin, taxane-anthracycline induction chemotherapy, radiation therapy, a platinum-based intensification high-dose CT, followed by leuprorelin and anastrazole for five years.", "Grade 4 hematologic toxicity was observed in all patients, no patient showed a decrease of cardiac ejection fraction and hot flashes and arthralgias were of moderate intensity.", "Of the patients treated with anastrozole, 3 (37.5%) reported toxicity, with 1 report each of decreased libido, leg swelling, and depression (12.5%). Toxicity was reported in 2 patients taking letrozole (40%), with both reporting peripheral edema, and 1 reporting hot flashes.", "Patients were treated with goserelin 3.6 mg subcutaneous monthly and began anastrozole 1-mg daily 21 days after the first injection of goserelin.", "The most common adverse events were fatigue (50%), arthralgias (53%), and hot flashes (59%).", "These studies were designed to evaluate the safety and efficacy of AIs in the following clinical settings: 1) as initial adjuvant therapy (the Arimidex, Tamoxifen, Alone or in Combination trial, Breast International Group Trial 1-98),", "AIs were tolerated well, and patients who received them experienced fewer thrombolic events and less endometrial cancer, hot flashes, night sweats, and vaginal bleeding compared with patients who receive tamoxifen.", "It has been suggested that the association of AI and GnRh analogues and AI could block the two routes of oestrogen production in males, and therefore this approach could increase efficacy. However, it could also enhance the rate of adverse events (hot flashes, sexual impotence, etc.).", "We reviewed therapeutic effects and harmful side effects in 33 patients with advanced or recurrent breast cancer who underwent treatment with Anastrozole 1 mg/day in our department.", "The most frequent harmful side effects were rise in total cholesterol, general fatigue, hot flashes and arthralgia (9.1%).", "We analyzed the changes in frequency and severity of menopausal symptoms in patients receiving tamoxifen or aromatase inhibitors and identified factors influencing these symptoms.", "Both first-line tamoxifen and aromatase inhibitors induced an increase in the occurrence and severity of hot flashes (p<0.0001 and p=0.014, respectively).", "To evaluate the efficacy and toxicity of the selective aromatase inhibitor anastrozole (Arimidex), we conducted a phase II trial in 53 women with asymptomatic recurrent/persistent müllerian cancer.", "Toxicity was modest (grade I) and infrequent, with the most common toxicities being fatigue and hot flashes.", "The first analysis of the ATAC (Arimidex, Tamoxifen Alone or in Combination) trial (median follow-up, 33 months) demonstrated that in adjuvant endocrine therapy for postmenopausal patients with early-stage breast cancer, anastrozole was superior to tamoxifen in terms of disease-free survival (DFS), time to recurrence (TTR), and incidence of contralateral breast cancer (CLBC).", "in that endometrial cancer (P = 0.007), vaginal bleeding and discharge (P < 0.001 for both), cerebrovascular events (P < 0.001), venous thromboembolic events (P < 0.001), and hot flashes (P < 0.001) all occurred less frequently in the anastrozole group, whereas musculoskeletal disorders and fractures (P < 0.001 for both) continued to occur less frequently in the tamoxifen group.", "reduced nausea, hot flashes, and abdominal discomfort caused almost twice as many patients to prefer to continue with letrozole therapy than with anastrozole" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/21378354", "http://www.ncbi.nlm.nih.gov/pubmed/23452648", "http://www.ncbi.nlm.nih.gov/pubmed/23314924", "http://www.ncbi.nlm.nih.gov/pubmed/17292609", "http://www.ncbi.nlm.nih.gov/pubmed/20975874", "http://www.ncbi.nlm.nih.gov/pubmed/20679610", "http://www.ncbi.nlm.nih.gov/pubmed/14584060", "http://www.ncbi.nlm.nih.gov/pubmed/23383974", "http://www.ncbi.nlm.nih.gov/pubmed/18072256", "http://www.ncbi.nlm.nih.gov/pubmed/18728707", "http://www.ncbi.nlm.nih.gov/pubmed/12902876", "http://www.ncbi.nlm.nih.gov/pubmed/15494636", "http://www.ncbi.nlm.nih.gov/pubmed/14675683", "http://www.ncbi.nlm.nih.gov/pubmed/22677000", "http://www.ncbi.nlm.nih.gov/pubmed/22370325", "http://www.ncbi.nlm.nih.gov/pubmed/15508444" ]

[ { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#type", "s": "http://linkedlifedata.com/resource/umls/label/A10338338", "o": "http://www.w3.org/2008/05/skos-xl#Label" }, { "p": "http://linkedlifedata.com/resource/umls/altMetaMap", "s": "http://linkedlifedata.com/resource/umls/id/C0878174", "o": "http://linkedlifedata.com/resource/umls/label/A11917539" } ]

[ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D019584", "http://www.biosemantics.org/jochem#4266381", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D006358" ]

[ "Inn1 associates with the contractile actomyosin ring at the end of mitosis and is needed for cytokinesis. Inn1 has a C2 domain at the amino terminus of the protein that is required for ingression of the plasma membrane during cytokinesis in budding yeast, whereas the remainder of the protein recruits Inn1 to the actomyosin ring" ]

[]

[ "Inn1 and Cyk3 regulate chitin synthase during cytokinesis in budding yeasts", "Our data support a model in which the C2-domain of Inn1 acts in conjunction with Cyk3 to regulate the catalytic domain of Chs2 during cytokinesis.", "Cdc14-dependent dephosphorylation of Inn1 contributes to Inn1-Cyk3 complex formation", "Cdc14 colocalizes with Inn1 at the cell division site and interacts with the C-terminal proline-rich domain of Inn1 that mediates its binding to the SH3-domain-containing proteins Hof1 and Cyk3. We show that phosphorylation of Inn1 by Cdk1 partially perturbs the interaction of Inn1 with Cyk3 thereby reducing the levels of Cyk3 at the cell division site. We propose that Cdc14 counteracts Cdk1 phosphorylation of Inn1 to facilitate Inn1-Cyk3 complex formation and so promote cytokinesis", "Targeted localization of Inn1, Cyk3 and Chs2 by the mitotic-exit network regulates cytokinesis in budding yeast", "Cyk3 acts in actomyosin ring independent cytokinesis by recruiting Inn1 to the yeast bud neck", "Role of Inn1 and its interactions with Hof1 and Cyk3 in promoting cleavage furrow and septum formation in S. cerevisiae", "we identified a novel factor that we call Inn1, which associates with the contractile actomyosin ring at the end of mitosis and is needed for cytokinesis. We show that Inn1 has a C2 domain at the amino terminus of the protein that is required for ingression of the plasma membrane, whereas the remainder of the protein recruits Inn1 to the actomyosin ring", " Our data indicate that recruitment of the C2 domain of Inn1 to the contractile actomyosin ring is crucial for ingression of the plasma membrane during cytokinesis in budding yeast", "We previously found that the C2-domain of the Saccharomyces cerevisiae Inn1 protein plays an essential but uncharacterised role at the cleavage site during cytokinesis.", "We propose that Cdc14 counteracts Cdk1 phosphorylation of Inn1 to facilitate Inn1-Cyk3 complex formation and so promote cytokinesis.", "Inn1 and Cyk3 regulate chitin synthase during cytokinesis in budding yeasts.", "Cyk3 acts in actomyosin ring independent cytokinesis by recruiting Inn1 to the yeast bud neck.", "Inn1 couples contraction of the actomyosin ring to membrane ingression during cytokinesis in budding yeast.", "Targeted localization of Inn1, Cyk3 and Chs2 by the mitotic-exit network regulates cytokinesis in budding yeast.", "We therefore propose that the MEN directly controls cytokinesis via targeting of Inn1, Cyk3 and Chs2 to the bud neck.", "Our data support a model in which the C2-domain of Inn1 acts in conjunction with Cyk3 to regulate the catalytic domain of Chs2 during cytokinesis.", "In addition to compensating for mutations in the Inn1 C2-domain, the dominant CHS2 alleles suppress cytokinesis defects produced by the lack of the Cyk3 protein.", "We propose that Cyk3 is part of an actomyosin ring independent cytokinesis pathway, which acts as a rescue mechanism to recruit Inn1 to the bud neck.", "We previously found that the C2-domain of the Saccharomyces cerevisiae Inn1 protein plays an essential but uncharacterised role at the cleavage site during cytokinesis.", "We propose that Cyk3 is part of an actomyosin ring independent cytokinesis pathway, which acts as a rescue mechanism to recruit Inn1 to the bud neck.", "The Inn1 C-terminal region is necessary for localization, and distinct PXXP motifs in this region mediate functionally important interactions with SH3 domains in the cytokinesis proteins Hof1 (an F-BAR protein) and Cyk3 (whose overexpression can restore PS formation in inn1Delta cells).", "Role of Inn1 and its interactions with Hof1 and Cyk3 in promoting cleavage furrow and septum formation in S. cerevisiae.", "We propose that Cdc14 counteracts Cdk1 phosphorylation of Inn1 to facilitate Inn1-Cyk3 complex formation and so promote cytokinesis." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/22956544", "http://www.ncbi.nlm.nih.gov/pubmed/22454527", "http://www.ncbi.nlm.nih.gov/pubmed/20442249", "http://www.ncbi.nlm.nih.gov/pubmed/19707790", "http://www.ncbi.nlm.nih.gov/pubmed/19528296", "http://www.ncbi.nlm.nih.gov/pubmed/18344988" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D048749", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0000910", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0032466", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0032467", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0032465" ]

[ "Growth hormone deficiency is implicated in Costello syndrome. Growth hormone therapy should be administered with caution due to possible severe side effects. Cortisol and sex hormone deficiencies were also implicated in Costello syndrome." ]

[ "Growth hormone deficiency" ]

[ "Measurements obtained after growth hormone exposure in 15 individuals were excluded in this analysis.", "Furthermore, we observed that RasGRF1 becomes phosphorylated in ARMS after stimulation by several pro-metastatic factors, such as SDF-1 and HGF/SF, as well as after exposure to growth-promoting Igf-2 and insulin.", "Progressively worsening hypertrophic cardiomyopathy in a child with newly diagnosed Costello syndrome while receiving growth hormone therapy.", "This report highlights two important concepts: the association of genetic syndromes with hypertrophic cardiomyopathy and the possibility of worsening severity of hypertrophic cardiomyopathy linked to growth hormone therapy.", "Oncogenic HRAS mutations cause prolonged PI3K signaling in response to epidermal growth factor in fibroblasts of patients with Costello syndrome.", "Statistical significance was achieved, despite the relatively small number of patients with BRAF and MEK1 mutations reported here, for polyhydramnios, growth hormone deficiency and the presence of more than one papilloma, which were less common in CFC compared to HRAS mutation positive patients. ", "Endocrine abnormalities including growth hormone deficiency, adrenal insufficiency, glucose intolerance, parathyroid adenoma with hyperprolactinemia and hypoglycemia have been described. Hypoglycemia has been documented due to growth hormone and cortisol deficiency. ", "Endocrine problems in this series were osteoporosis, central hypogonadism, and delayed puberty.", "Growth hormone deficiency in Costello syndrome.", "We report on three patients with Costello syndrome and isolated growth hormone (GH) deficiency treated with biosynthetic GH. To our knowledge, these are the only patients with Costello syndrome who have been successfully treated for GH deficiency. We review the pathophysiology of Costello syndrome and highlight the recent recommendations of tumor screening and cardiac surveillance in this population, of particular relevance to those receiving GH therapy.", "Costello syndrome with growth hormone deficiency and hypoglycemia: a new report and review of the endocrine associations.", "We describe an 18-month-old boy with Costello syndrome (CS) with proven partial growth hormone (GH) deficiency and hypoglycemic episodes. The hypoglycemia is deemed to be due to cortisol deficiency. This report represents the second published case of cortisol deficiency in the CS.", "We present the case of a boy with Costello syndrome who developed osteofibrous dysplasia during a phase of growth hormone therapy.", "Thus, although osteofibrous dysplasia in Costello syndrome has not been reported before, growth hormone therapy should be used under close supervision in children with this syndrome.", "Endocrinological investigations revealed a partial deficiency of growth hormone." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/15940703", "http://www.ncbi.nlm.nih.gov/pubmed/15316968", "http://www.ncbi.nlm.nih.gov/pubmed/17551924", "http://www.ncbi.nlm.nih.gov/pubmed/22752028", "http://www.ncbi.nlm.nih.gov/pubmed/22887473", "http://www.ncbi.nlm.nih.gov/pubmed/16278907", "http://www.ncbi.nlm.nih.gov/pubmed/14564166", "http://www.ncbi.nlm.nih.gov/pubmed/15316966", "http://www.ncbi.nlm.nih.gov/pubmed/20307337", "http://www.ncbi.nlm.nih.gov/pubmed/19035362", "http://www.ncbi.nlm.nih.gov/pubmed/18483625", "http://www.ncbi.nlm.nih.gov/pubmed/21438134", "http://www.ncbi.nlm.nih.gov/pubmed/22821884", "http://www.ncbi.nlm.nih.gov/pubmed/8168845", "http://www.ncbi.nlm.nih.gov/pubmed/19258709" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D056685", "http://www.disease-ontology.org/api/metadata/DOID:0050469", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D006728" ]

[ "RPC components include the essential initiation and elongation factor, Cdc45, the checkpoint mediator Mrc1, the Tof1-Csm3 complex that allows replication forks to pause at protein-DNA barriers, the histone chaperone FACT (facilitates chromatin transcription) and Ctf4, which helps to establish sister chromatid cohesion. RPCs also interact with Mcm10 and topoisomerase I.", "RPCs also interact with Mcm10 and topoisomerase I. Others have found recently that the Mrc1 subunit of RPCs binds DNA polymerase epsilon, which synthesises the leading strand at DNA replication forks. Here, we show that the RPC associates with DNA polymerase alpha that primes each Okazaki fragment during lagging strand synthesis. During initiation, GINS is essential for a specific subset of RPC proteins to interact with MCM. GINS is also important for the normal progression of DNA replication forks, and we show that it is required after initiation to maintain the association between MCM and Cdc45 within RPCs. This interaction requires the RPC components Mrc1 and Ctf4, both of which associate with a tetratricopeptide repeat (TPR) domain located at the amino terminus of Dia2. RPC components include the essential initiation and elongation factor, Cdc45, the checkpoint mediator Mrc1, the Tof1-Csm3 complex that allows replication forks to pause at protein-DNA barriers, the histone chaperone FACT (facilitates chromatin transcription) and Ctf4, which helps to establish sister chromatid cohesion. " ]

[ "Cdc45", "Mrc1", "Tof1-Csm3 complex", "FACT", "Ctf4" ]

[ "This interaction requires the RPC components Mrc1 and Ctf4, both of which associate with a tetratricopeptide repeat (TPR) domain located at the amino terminus of Dia2", "Here we show that SCF(Dia2) associates with the replisome progression complex (RPC) that assembles around the MCM2-7 helicase at DNA replication forks", "We found previously that many regulatory proteins assemble around the MCM2-7 helicase at yeast replication forks to form the replisome progression complex (RPC), which might link MCM2-7 to other replisome components", "Here, we show that the RPC associates with DNA polymerase alpha that primes each Okazaki fragment during lagging strand synthesis. Our data indicate that a complex of the GINS and Ctf4 components of the RPC is crucial to couple MCM2-7 to DNA polymerase alpha", "Others have found recently that the Mrc1 subunit of RPCs binds DNA polymerase epsilon, which synthesises the leading strand at DNA replication forks", "we show that the GINS (go ichi ni san) complex allows the MCM (minichromosome maintenance) helicase to interact with key regulatory proteins in large replisome progression complexes (RPCs) that are assembled during initiation and disassembled at the end of S phase", "RPC components include the essential initiation and elongation factor, Cdc45, the checkpoint mediator Mrc1, the Tof1-Csm3 complex that allows replication forks to pause at protein-DNA barriers, the histone chaperone FACT (facilitates chromatin transcription) and Ctf4, which helps to establish sister chromatid cohesion. RPCs also interact with Mcm10 and topoisomerase I", "During initiation, GINS is essential for a specific subset of RPC proteins to interact with MCM. GINS is also important for the normal progression of DNA replication forks, and we show that it is required after initiation to maintain the association between MCM and Cdc45 within RPCs", "We found previously that many regulatory proteins assemble around the MCM2-7 helicase at yeast replication forks to form the replisome progression complex (RPC), which might link MCM2-7 to other replisome components.", "Here we show that SCF(Dia2) associates with the replisome progression complex (RPC) that assembles around the MCM2-7 helicase at DNA replication forks [6].", "Compared with wild type, hydroxyurea-treated ctf18жд cells exhibited increased chromatin association of replisome progression complex components including Cdc45, Ctf4, and GINS complex subunits, the polymerase processivity clamp PCNA and the single-stranded DNA-binding complex RPA.", "The amino-terminal TPR domain of Dia2 tethers SCF(Dia2) to the replisome progression complex.", "Ctf4 is a protein conserved in eukaryotes and a constituent of the replisome progression complex.", "Eukaryotic GINS also links with other key proteins at the fork to maintain an active replisome progression complex.", "Dia2 has previously been implicated in the control of replication and genome stability via its interaction with the replisome progression complex.", "The Cdc45-MCM-GINS complex could constitute the core of a larger macromolecular structure that has been termed the \"replisome progression complex\".", "FACT does not associate with the Mcm2-7 helicase at replication origins during G1 phase but is subsequently incorporated into the replisome progression complex independently of histone binding and uniquely among histone chaperones.", "Our data indicate that a complex of the GINS and Ctf4 components of the RPC is crucial to couple MCM2-7 to DNA polymerase alpha.", "Replisome progression complex links DNA replication to sister chromatid cohesion in Xenopus egg extracts.", "On the basis of the physical interactions between AND-1 and DNA polymerases, we discuss a model to describe how replisome progression complex establishes sister chromatid cohesion.", "The components of the replisome that preserve genomic stability by controlling the progression of eukaryotic DNA replication forks are poorly understood.", "RPC components include the essential initiation and elongation factor, Cdc45, the checkpoint mediator Mrc1, the Tof1-Csm3 complex that allows replication forks to pause at protein-DNA barriers, the histone chaperone FACT (facilitates chromatin transcription) and Ctf4, which helps to establish sister chromatid cohesion." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/22918584", "http://www.ncbi.nlm.nih.gov/pubmed/16930479", "http://www.ncbi.nlm.nih.gov/pubmed/16531994", "http://www.ncbi.nlm.nih.gov/pubmed/23499444", "http://www.ncbi.nlm.nih.gov/pubmed/19496828", "http://www.ncbi.nlm.nih.gov/pubmed/21701592", "http://www.ncbi.nlm.nih.gov/pubmed/19913425", "http://www.ncbi.nlm.nih.gov/pubmed/21505101", "http://www.ncbi.nlm.nih.gov/pubmed/19661920", "http://www.ncbi.nlm.nih.gov/pubmed/19910927", "http://www.ncbi.nlm.nih.gov/pubmed/16483939", "http://www.ncbi.nlm.nih.gov/pubmed/19622120" ]

[]

[ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0030894" ]

[ "An absent word of a word y of length n is a word that does not occur in y. It is a minimal absent word if all its proper factors occur in y. Minimal absent words have been computed in genomes of organisms from all domains of life; their computation also provides a fast alternative for measuring approximation in sequence comparison." ]

[]

[ " We show how absent words relate to the repetitions and structure of the data, and define a new and larger class of absent words, called minimal absent words, that still captures the essential properties of the shortest absent words introduced in recent works. The words of this new class are minimal in the sense that if their leftmost or rightmost character is removed, then the resulting word is no longer an absent word. ", "An absent word (also called a forbidden word or an unword in other contexts) in a sequence is a segment that does not appear in the given sequence. It is a minimal absent word if all its proper factors occur in the given sequence.", "An absent word of a word y of length n is a word that does not occur in y. It is a minimal absent word if all its proper factors occur in y. Minimal absent words have been computed in genomes of organisms from all domains of life; their computation also provides a fast alternative for measuring approximation in sequence comparison.", " We show how absent words relate to the repetitions and structure of the data, and define a new and larger class of absent words, called minimal absent words, that still captures the essential properties of the shortest absent words introduced in recent works. The words of this new class are minimal in the sense that if their leftmost or rightmost character is removed, then the resulting word is no longer an absent word.", "We show how absent words relate to the repetitions and structure of the data, and define a new and larger class of absent words, called minimal absent words, that still captures the essential properties of the shortest absent words introduced in recent works. The words of this new class are minimal in the sense that if their leftmost or rightmost character is removed, then the resulting word is no longer an absent word." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/19426495", "http://www.ncbi.nlm.nih.gov/pubmed/22974263", "http://www.ncbi.nlm.nih.gov/pubmed/25526884" ]

[]

[]

[ "About 30% of Hirschsprung disease (HSCR) cases are syndromic. Hitherto, the disease causing gene has been identified for eight Mendelian syndromes with HSCR: congenital central hypoventilation (CCHS), Mowat-Wilson (MWS), Bardet-Biedl (BBS), Shah-Waardenburg (WS4), cartilage-hair-hypoplasia (CHH), Smith-Lemli-Opitz (SLO), Goldberg-Sprintzsen (GSS), and hydrocephalus due to congenital stenosis of the aqueduct of sylvius (HSAS).", "In CCHS patients, the weak predisposing haplotype of the RET gene can be regarded as a quantitative trait, being a risk factor for the HSCR phenotype, while in MWS, for which the HSCR penetrance is high, the role of the RET predisposing haplotype is not significant." ]

[]

[ "Hirschsprung's disease (HSCR) is a fairly frequent cause of intestinal obstruction in children. It is characterized as a sex-linked heterogonous disorder with variable severity and incomplete penetrance giving rise to a variable pattern of inheritance. Although Hirschsprung's disease occurs as an isolated phenotype in at least 70% of cases, it is not infrequently associated with a number of congenital abnormalities and associated syndromes, demonstrating a spectrum of congenital anomalies. Certain of these syndromic phenotypes have been linked to distinct genetic sites, indicating underlying genetic associations of the disease and probable gene-gene interaction, in its pathogenesis. These associations with HSCR include Down's syndrome and other chromosomal anomalies, Waardenburg syndrome and other Dominant sensorineural deafness, the Congenital Central Hypoventilation and Mowat-Wilson and other brain-related syndromes, as well as the MEN2 and other tumour associations", "On the other hand, about 30% of HSCR are syndromic. Hitherto, the disease causing gene has been identified for eight Mendelian syndromes with HSCR: congenital central hypoventilation (CCHS), Mowat-Wilson (MWS), Bardet-Biedl (BBS), Shah-Waardenburg (WS4), cartilage-hair-hypoplasia (CHH), Smith-Lemli-Opitz (SLO), Goldberg-Sprintzsen (GSS), and hydrocephalus due to congenital stenosis of the aqueduct of sylvius (HSAS)", "The syndromic HSCR entities studied were congenital central hypoventilation (CCHS) and Mowat-Wilson syndrome (MWS), caused by PHOX2B and ZFHX1B gene mutations, respectively", "The RET locus was genotyped in 143 CCHS patients, among whom 44 had HSCR, and in 30 MWS patients, among whom 20 had HSCR", "RET was shown to act as a modifier gene for the HSCR phenotype in patients with CCHS but not with MWS", "These associations with HSCR include Down's syndrome and other chromosomal anomalies, Waardenburg syndrome and other Dominant sensorineural deafness, the Congenital Central Hypoventilation and Mowat-Wilson and other brain-related syndromes, as well as the MEN2 and other tumour associations", "Hitherto, the disease causing gene has been identified for eight Mendelian syndromes with HSCR: congenital central hypoventilation (CCHS), Mowat-Wilson (MWS), Bardet-Biedl (BBS), Shah-Waardenburg (WS4), cartilage-hair-hypoplasia (CHH), Smith-Lemli-Opitz (SLO), Goldberg-Sprintzsen (GSS), and hydrocephalus due to congenital stenosis of the aqueduct of sylvius (HSAS).", "The syndromic HSCR entities studied were congenital central hypoventilation (CCHS) and Mowat-Wilson syndrome (MWS), caused by PHOX2B and ZFHX1B gene mutations, respectively.", "RET was shown to act as a modifier gene for the HSCR phenotype in patients with CCHS but not with MWS.", "In CCHS patients, the weak predisposing haplotype of the RET gene can be regarded as a quantitative trait, being a risk factor for the HSCR phenotype, while in MWS, for which the HSCR penetrance is high, the role of the RET predisposing haplotype is not significant.", "These associations with HSCR include Down's syndrome and other chromosomal anomalies, Waardenburg syndrome and other Dominant sensorineural deafness, the Congenital Central Hypoventilation and Mowat-Wilson and other brain-related syndromes, as well as the MEN2 and other tumour associations.", "Hitherto, the disease causing gene has been identified for eight Mendelian syndromes with HSCR: congenital central hypoventilation (CCHS), Mowat-Wilson (MWS), Bardet-Biedl (BBS), Shah-Waardenburg (WS4), cartilage-hair-hypoplasia (CHH), Smith-Lemli-Opitz (SLO), Goldberg-Sprintzsen (GSS), and hydrocephalus due to congenital stenosis of the aqueduct of sylvius (HSAS).", "The syndromic HSCR entities studied were congenital central hypoventilation (CCHS) and Mowat-Wilson syndrome (MWS), caused by PHOX2B and ZFHX1B gene mutations, respectively.", "These associations with HSCR include Downs syndrome and other chromosomal anomalies, Waardenburg syndrome and other Dominant sensorineural deafness, the Congenital Central Hypoventilation and Mowat-Wilson and other brain-related syndromes, as well as the MEN2 and other tumour associations.", "METHODS: The syndromic HSCR entities studied were congenital central hypoventilation (CCHS) and Mowat-Wilson syndrome (MWS), caused by PHOX2B and ZFHX1B gene mutations, respectively.", "These associations with HSCR include Down's syndrome and other chromosomal anomalies, Waardenburg syndrome and other Dominant sensorineural deafness, the Congenital Central Hypoventilation and Mowat-Wilson and other brain-related syndromes, as well as the MEN2 and other tumour associations.", "Hitherto, the disease causing gene has been identified for eight Mendelian syndromes with HSCR: congenital central hypoventilation (CCHS), Mowat-Wilson (MWS), Bardet-Biedl (BBS), Shah-Waardenburg (WS4), cartilage-hair-hypoplasia (CHH), Smith-Lemli-Opitz (SLO), Goldberg-Sprintzsen (GSS), and hydrocephalus due to congenital stenosis of the aqueduct of sylvius (HSAS)", "These associations with HSCR include Down's syndrome and other chromosomal anomalies, Waardenburg syndrome and other Dominant sensorineural deafness, the Congenital Central Hypoventilation and Mowat-Wilson and other brain-related syndromes, as well as the MEN2 and other tumour associations", "The frequent, low penetrant, predisposing allele of the RET gene can be regarded as a risk factor for the HSCR phenotype in CCHS, BBS, and Down syndrome, while its role is not significant in MWS and WS4", "RET acts as a modifier gene for the HSCR phenotype in patients with CCHS, BBS, and Down syndrome, but not in patients with MWS and WS4", "The syndromic HSCR entities studied were congenital central hypoventilation (CCHS) and Mowat-Wilson syndrome (MWS), caused by PHOX2B and ZFHX1B gene mutations, respectively", "Hitherto, the disease causing gene has been identified for eight Mendelian syndromes with HSCR: congenital central hypoventilation (CCHS), Mowat-Wilson (MWS), Bardet-Biedl (BBS), Shah-Waardenburg (WS4), cartilage-hair-hypoplasia (CHH), Smith-Lemli-Opitz (SLO), Goldberg-Sprintzsen (GSS), and hydrocephalus due to congenital stenosis of the aqueduct of sylvius (HSAS)", "These data highlight the pivotal role of the RET gene in both isolated and syndromic HSCR." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/23001136", "http://www.ncbi.nlm.nih.gov/pubmed/16443855", "http://www.ncbi.nlm.nih.gov/pubmed/17397038" ]

[]

[]

[ "The commonest CFTR mutation, deltaF508, is found in 74.1% of all CF chromosomes. In the Caucasian CF population, 57.5% are deltaF508 homozygotes but the UK ISC CF population with only 24.7%, has significantly fewer deltaF508 homozygotes patients (95% confidence interval (CI) 0.2-0.4)." ]

[ "deltaF508" ]

[ "Exposure to WCS caused a pronounced reduction in CFTR activity in both CFTR (+/+) cells and F508del CFTR (+/-) cell", "Moreover, the common heterozygous F508del/5T and F508del/R117H were observed in 17 and 4% of CBAVD cases respectively, and the allele frequency in CBAVD was 17% for F508del, 25% for 5T and 3% for R117H.", "The most common mutations were p.F508del (DeltaF508) (18.1%), c.2183_2184delAAinsG (2183AA>G) (6.5%), p.S466X (5.8%), p.N1303K (4.3%), c.2789+5G>A (4.3%), p.G542X (3.6%), c.3120+1G>A (3.6%), p.R334W (2.9%) and c.3130delA (2.9%). These 9 types of mutant CFTR genes totaled for 52% of all CFTR genes derived from the 69 Iranian CF patients. Eight mutations, c.406-8T>C, p.A566D, c.2576delA, c.2752-1_2756delGGTGGCinsTTG, p.T1036I, p.W1145R, c.3850-24G>A, c.1342-?_1524+?del, were found for the first time in this study.", "The commonest CFTR mutation, deltaF508, is found in 74.1% of all CF chromosomes. In the Caucasian CF population, 57.5% are deltaF508 homozygotes but the UK ISC CF population with only 24.7%, has significantly fewer deltaF508 homozygotes patients (95% confidence interval (CI) 0.2-0.4).", "Although the major mutation that results in a single amino acid deletion (F508) accounts for 70% of the disease alleles, more than 550 additional mutant alleles of different forms have been detected.", "Besides the major 3-bp deletion, delta F508 that was found on 73% of German CF chromosomes, more than 50 other missense, nonsense, frame-shift, and splice-site mutations have already been identified.", "However, the CFTR mutation delta F508 is the most common reason for the frequently inherited disease among the Caucasian population. Maturation and processing of delta F508-CFTR is defective which leads to expression of only very little but functional CFTR in the cell membrane.", "The most common disease-causing mutation, DeltaF508, is found in 70% of patients with cystic fibrosis. ", " Cystic fibrosis is the most common inherited lethal disease in Caucasians. It is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR), of which the cftr ΔF508 mutation is the most common.", "Cystic fibrosis is the most common inherited lethal disease in Caucasians. It is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR), of which the cftr ΔF508 mutation is the most common.", "Caucasians (eight of nine), Northern Irish (four of five), and Israelis (three of three) also occurred in other Caucasian groups. The preponderance of previously reported mutations in these three groups suggested that a subset of the non-delta F508 mutations occur in common among Caucasians." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/11014930", "http://www.ncbi.nlm.nih.gov/pubmed/8222279", "http://www.ncbi.nlm.nih.gov/pubmed/1376017", "http://www.ncbi.nlm.nih.gov/pubmed/17662673", "http://www.ncbi.nlm.nih.gov/pubmed/8825494", "http://www.ncbi.nlm.nih.gov/pubmed/24517344", "http://www.ncbi.nlm.nih.gov/pubmed/23148214", "http://www.ncbi.nlm.nih.gov/pubmed/22081250", "http://www.ncbi.nlm.nih.gov/pubmed/12357328", "http://www.ncbi.nlm.nih.gov/pubmed/19837664" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009154", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D003550", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D006801" ]

[ "Aip1, Ede1 and Inn1 are CDK targets whose dephosphorylation is required for cytokinesis." ]

[ "Aip1", "Ede1", "Inn1" ]

[ "We use phosphoproteome analysis of mitotic exit to identify Cdk targets that are dephosphorylated at the time of cytokinesis. We then apply a new and widely applicable tool to generate conditionally phosphorylated proteins to identify those whose dephosphorylation is required for cytokinesis. This approach identifies Aip1, Ede1 and Inn1 as cytokinetic regulators. Our results suggest that cytokinesis is coordinately controlled by the master cell cycle regulator Cdk together with its counteracting phosphatase and that it is executed by concerted dephosphorylation of Cdk targets involved in several cell biological processes." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/25371407" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D048749", "http://amigo.geneontology.org/amigo/term/GO:0032465", "http://amigo.geneontology.org/amigo/term/GO:0000910", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D018844" ]

[ "A significant percentage of the more than 1 million copies of Alu elements was shown to be transrcribed. Free Alu RNAs are known to be transcribed by Pol III from their own promoter. On the other hand, embedded Alu RNAs are transcribed by Pol II as part of protein- and non-protein-coding RNAs. Recent studies have demonstrated that both free and embedded Alu RNAs play a major role in post transcriptional regulation of gene expression." ]

[ "yes" ]

[ "Alu RNAs in the human transcriptome", "Alu elements can be transcribed in two different ways, by two independent polymerases", "'Free Alu RNAs' are transcribed by Pol III from their own promoter", "'embedded Alu RNAs' are transcribed by Pol II as part of protein- and non-protein-coding RNAs", "Recent studies have demonstrated that both free and embedded Alu RNAs play a major role in post transcriptional regulation of gene expression", "Alu RNAs transcribed from these elements are present at low levels at normal cell growth but various stress conditions increase their abundance", "Alu RNAs are known to bind the cognate proteins SRP9/14", "Increased level of polymerase III transcribed Alu RNA in hepatocellular carcinoma tissue", "we used primer extension analysis to determine the level of polymerase III directed Alu RNA and found an increased expression of Alu RNA in hepatocellular carcinoma", "Widespread RNA editing of embedded alu elements in the human transcriptome", "Transcribed Alu sequences can alter splicing patterns by generating new exons", "In the vast majority of edited RNAs, A-to-I substitutions are clustered within transcribed sense or antisense Alu sequences", "Alu-associated RNA editing may be a mechanism for marking nonstandard transcripts, not destined for translation", "the case of transcribed Alus", "Differential levels of Alu RNA during different conditions of stress also await clear functional understanding", "Alu expression in human cell lines and their retrotranspositional potential", "Alu expression likely varies by cell type, growth conditions and transformation state", "The vast majority of Alu loci potentially transcribed by RNA pol III lack important sequence features for retrotransposition and the majority of potentially active Alu loci in the genome (scored high ERP) belong to young Alu subfamilies", "We suggest that the genomic sequences upstream from most Alu elements and 7SL pseudogenes do not contain this element, and consequently that only a small subset of such sequences can be transcribed in vivo.", "These similarities suggest that some Alu family sequences are mobile genetic elements that can transpose to new chromosomal loci using as an intermediate a cDNA copy of an RNA transcribed from the Alu family element by RNA polymerase III.", "Primate and rodent genomes are populated with hundreds of thousands copies of Alu and B1 elements dispersed by retroposition, i.e., by genomic reintegration of their reverse transcribed RNAs.", "Members of this family are readily transcribed in vitro by RNA polymerase III, but RNA corresponding to only a small sub-set of Alu elements has been found in vivo.", "Alu interspersed repetitive elements possess internal RNA polymerase III promoters which are strongly transcribed in vitro, yet these elements are nearly silent in somatic cells.", "The amplification of genomic Alu elements by retroposition, i.e. by reintegration of reverse-transcribed RNA, suggests that Alu RNA plays an important role in this process.", "We report enzymatic studies of the secondary structure of Alu RNAs transcribed in vitro from two recently retroposed Alu elements.", "The results of this study indicate that Alu and 7SL RNA gene sequences interact with cellular factors that are important for HeLa cell proliferation and suggest that these pol III-transcribed elements may be involved in the regulation of cellular growth.", "Then we used primer extension analysis to determine the level of polymerase III directed Alu RNA and found an increased expression of Alu RNA in hepatocellular carcinoma", "Alu interspersed repetitive elements possess internal RNA polymerase III promoters which are strongly transcribed in vitro, yet these elements are nearly silent in somatic cells", "'Free Alu RNAs' are transcribed by Pol III from their own promoter, while 'embedded Alu RNAs' are transcribed by Pol II as part of protein- and non-protein-coding RNAs", "We report enzymatic studies of the secondary structure of Alu RNAs transcribed in vitro from two recently retroposed Alu elements", "Transcribed Alu sequences can alter splicing patterns by generating new exons, but other impacts of intragenic Alu elements on their host RNA are largely unexplored", "Both 7SL genes and Alu elements are transcribed by RNA polymerase III, and we show here that the internal 7SL promoter lies within the Alu-like part of the 7SL gene", "Each group revealed a divergent pattern of transcribed Alu elements" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/1709156", "http://www.ncbi.nlm.nih.gov/pubmed/8093066", "http://www.ncbi.nlm.nih.gov/pubmed/17514354", "http://www.ncbi.nlm.nih.gov/pubmed/22716230", "http://www.ncbi.nlm.nih.gov/pubmed/1704372", "http://www.ncbi.nlm.nih.gov/pubmed/8366099", "http://www.ncbi.nlm.nih.gov/pubmed/16682445", "http://www.ncbi.nlm.nih.gov/pubmed/15342557", "http://www.ncbi.nlm.nih.gov/pubmed/21987713", "http://www.ncbi.nlm.nih.gov/pubmed/6173130", "http://www.ncbi.nlm.nih.gov/pubmed/20424511", "http://www.ncbi.nlm.nih.gov/pubmed/7528809", "http://www.ncbi.nlm.nih.gov/pubmed/2415825", "http://www.ncbi.nlm.nih.gov/pubmed/15593371" ]

[]

[]

[ "Prolamellar body (PLB) is a highly organized lipid structure, which is the main site of accumulation of the ternary light-harvesting POR complex LHPP (light-harvesting NADPH:protochlorophyllide oxidoreductase:protochlorophyllide). Prolamellar bodies have been discovered in etioplasts with the use of thin section electron microscopy. Etioplasts develop in the place of chloroplasts in the dark. During skotomorphogenesis in angiosperms, NADPH:protochlorophyllide oxidoreductase (POR) forms the photolabile NADPH-POR-protochlorophyllide (Pchlide) ternary complexes. Prolamellar bodies (PLBs) efficiently capture the light energy for photo conversion in etioplasts. Upon illumination, the etioplasts transformed into regular chloroplasts. PLBs are formed not only in etioplasts but also in chloroplasts in young developing leaves during the night." ]

[ "etioplasts (mainly)", "chloroplasts (in young developing leaves during the night)" ]

[ "CPP1 depletion also causes reduced POR accumulation in etioplasts of dark-grown plants and as a result impairs the formation of prolamellar bodies, which subsequently affects chloroplast biogenesis upon illumination.", "Prolamellar bodies (PLBs) isolated from etiolated wheat seedlings were studied with the use of atomic force microscopy (AFM), transmission electron microscopy (TEM) and fluorescence spectroscopy", "TEM analyses confirmed that PLBs of wheat leaf etioplasts also had an average diameter of appr. 1μm", "etioplasts with prolamellar bodies (PLBs) and photoactive, 655nm emitting Pchlide form accumulated primarily in the basal leaf regions after 2 weeks of regeneration. When these latter leaves were illuminated with continuous light for 3 days, the etioplasts transformed into regular chloroplasts", "POR complex assembly (including LHPP and POR dimers) did not affect the formation of prolamellar bodies (PLBs) that function for efficient capture of light energy for photo conversion in etioplasts.", "Etioplasts that develop in the place of chloroplasts in the dark contain a highly organized lipid structure termed prolamellar body (PLB), which is the main site of accumulation of the ternary Pchlide:POR:NADPH complexes.", "During skotomorphogenesis in angiosperms, NADPH:protochlorophyllide oxidoreductase (POR) forms an aggregate of photolabile NADPH-POR-protochlorophyllide (Pchlide) ternary complexes localized to the prolamellar bodies within etioplasts.", "The content of the supramolecular light-harvesting POR complex LHPP (light-harvesting NADPH:protochlorophyllide oxidoreductase:protochlorophyllide) and the density of prolamellar bodies in etioplasts are decreased in the mutant.", "The Arabidopsis porB-1 porC-1 mutant displays a severe xantha (highly chlorophyll-deficient) phenotype characterized by smaller prolamellar bodies in etioplasts", "The most notable contributions of thin section electron microscopy include the elucidation of the 3-D organization of thylakoid membranes, the discovery of prolamellar bodies in etioplasts", "This resulted in the recovery of thylakoid membrane stacking in chloroplasts in the light, and the formation of prolamellar bodies and plastoglobuli in etioplasts in the dark.", "The prolamellar body (PLB) proteome of dark-grown wheat leaves was characterized. PLBs are formed not only in etioplasts but also in chloroplasts in young developing leaves during the night", "A fraction of highly purified prolamellar bodies was isolated from etioplasts of wheat (Triticum aestivum L.", "The highest specific activity of the enzyme in etiolated leaf tissue was confirmed to be in the fraction of prolamellar bodies.", "This work reveals a new view on the formation of prolamellar bodies and provides new clues about the function of POR in the etioplast-chloroplast transition.", "The Arabidopsis porB-1 porC-1 mutant displays a severe xantha (highly chlorophyll-deficient) phenotype characterized by smaller prolamellar bodies in etioplasts and decreased thylakoid stacking in chloroplasts.", "Transmission electron microscopy revealed partially developed, agranal plastids in the dark-grown mutant, unlike wild-type seedlings that contain etioplasts with prolamellar bodies.", "Organization of protochlorophyllide oxidoreductase in prolamellar bodies isolated from etiolated carotenoid-deficient wheat leaves as revealed by fluorescence probes.", "In fully etiolated leaves lamellae are absent and the prolamellar bodies become quite large, presumably because of inhibition of the fusion step which appears to require chlorophyll.", "POR is a peripheral membrane protein that accumulates to high levels in the prolamellar bodies of vascular plant etioplasts and is present at low levels in the thylakoid membranes of developing and mature plastids.", "This work reveals a new view on the formation of prolamellar bodies and provides new clues about the function of POR in the etioplast-chloroplast transition.", "The results presented in this paper are not consistent with the hypothesis that the molar ratio of MGDG/DGDG is responsible for the tubular structure of prolamellar bodies in etioplasts." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/24232321", "http://www.ncbi.nlm.nih.gov/pubmed/23415648", "http://www.ncbi.nlm.nih.gov/pubmed/22704664", "http://www.ncbi.nlm.nih.gov/pubmed/24151298", "http://www.ncbi.nlm.nih.gov/pubmed/18071923", "http://www.ncbi.nlm.nih.gov/pubmed/12602886", "http://www.ncbi.nlm.nih.gov/pubmed/11532175", "http://www.ncbi.nlm.nih.gov/pubmed/23777838", "http://www.ncbi.nlm.nih.gov/pubmed/14581621", "http://www.ncbi.nlm.nih.gov/pubmed/10080697", "http://www.ncbi.nlm.nih.gov/pubmed/22278767", "http://www.ncbi.nlm.nih.gov/pubmed/24249610", "http://www.ncbi.nlm.nih.gov/pubmed/20012672", "http://www.ncbi.nlm.nih.gov/pubmed/22573443", "http://www.ncbi.nlm.nih.gov/pubmed/12447549", "http://www.ncbi.nlm.nih.gov/pubmed/1467651", "http://www.ncbi.nlm.nih.gov/pubmed/20616380", "http://www.ncbi.nlm.nih.gov/pubmed/16228577", "http://www.ncbi.nlm.nih.gov/pubmed/16229815", "http://www.ncbi.nlm.nih.gov/pubmed/13376637", "http://www.ncbi.nlm.nih.gov/pubmed/19222806", "http://www.ncbi.nlm.nih.gov/pubmed/16663945" ]

[]

[ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0009541", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0043226" ]

[ "Mepolizumab and reslizumab are monoclonal antibodies that target and neutralize interleukin 5. They have been shown to reduce eosinophil counts and they are used for the treatment of refractory asthma (associated with eosiniphilia) and other eosinophilic diseases." ]

[ "monoclonal antibodies", "treatment for refractory asthma", "treatment for eosinophilic disease", "neutralize interleukin 5", "reduce eosinophil counts" ]

[ "The most promising agents are targeted against cytokines of Th2 pattern and related receptors, such as IL-2 (daclizumab) and IL-13 (lebrikizumab) or IL-5 in patients with hypereosinophilia (mepolizumab, reslizumab and benralizumab).", "Patients with severe asthma or COPD have often a suboptimal symptom control due to inadequate treatment. ", "For example, patients with the hypereosinophilic syndrome have received mepolizumab, an anti-IL-5 monoclonal antibody, for as long as 6 years and have not developed any characteristic set of adverse events. Safety data for reslizumab, another anti-IL-5 monoclonal antibody, and benralizumab, a monoclonal antibody to the IL-5 receptor α-chain, are comparatively limited, especially for benralizumab, although reports of administration of these antibodies to humans suggest that they are well tolerated.", "IL-5 antagonist therapies in current development include two monoclonal anti-IL-5 antibodies (mepolizumab, reslizumab), a monoclonal antibody directed at the IL-5 receptor (benralizumab), and anti-sense oligonucleotide therapy (TPI ASM8).", "In patients with severe, refractory asthma associated with eosinophilia, however, clinical trials have demonstrated significant reductions in asthma exacerbations. Clinical studies in other disorders, particularly eosinophilic esophagitis and hypereosinophilic syndrome, have also shown significant improvements in blood and/or tissue eosinophilia and variable alterations in clinical disease activity. Strategies aimed at the inhibition of IL-5 may hold great promise in the treatment of eosinophilic diseases.", "Two monoclonal antibodies have been designed to neutralize IL-5 (mepolizumab and reslizumab). Both antibodies have demonstrated the ability to reduce blood and tissue eosinophil counts. ", "Two monoclonal antibodies have been designed to neutralize IL-5 (mepolizumab and reslizumab).", "To date, two humanized monoclonal antibodies, mepolizumab and reslizumab, have been developed that bind to human IL-5.", "Monoclonal antibodies directed towards interleukin-5, such as mepolizumab or reslizumab, were shown to be very effective at reducing blood and airways eosinophilia.", "IL-5 antagonist therapies in current development include two monoclonal anti-IL-5 antibodies (mepolizumab, reslizumab), a monoclonal antibody directed at the IL-5 receptor (benralizumab), and anti-sense oligonucleotide therapy (TPI ASM8).", "The most promising agents are targeted against cytokines of Th2 pattern and related receptors, such as IL-2 (daclizumab) and IL-13 (lebrikizumab) or IL-5 in patients with hypereosinophilia (mepolizumab, reslizumab and benralizumab).", "Asthma is a chronic inflammatory disease that often features eosinophilia, especially in its most severe forms. Monoclonal antibodies directed towards interleukin-5, such as mepolizumab or reslizumab, were shown to be very effective at reducing blood and airways eosinophilia. " ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/22541618", "http://www.ncbi.nlm.nih.gov/pubmed/21824072", "http://www.ncbi.nlm.nih.gov/pubmed/26285457", "http://www.ncbi.nlm.nih.gov/pubmed/25671117", "http://www.ncbi.nlm.nih.gov/pubmed/22092535", "http://www.ncbi.nlm.nih.gov/pubmed/23742015", "http://www.ncbi.nlm.nih.gov/pubmed/24275927", "http://www.ncbi.nlm.nih.gov/pubmed/20565230", "http://www.ncbi.nlm.nih.gov/pubmed/19037962" ]

[]

[ "http://www.biosemantics.org/jochem#4002251", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D015848" ]

[ "Itaconic acid levels are elevetad in immune defence." ]

[ "Immune Defence" ]

[ "taconic acid (P = 0.0003), with a false discovery rate of 0.012, was found to be significantly more abundant in women who subsequently developed gestational diabetes mellitus, when compared to controls with uncomplicated pregnancies.", "Using a gain-and-loss-of-function approach in both mouse and human immune cells, we found Irg1 expression levels correlating with the amounts of itaconic acid, a metabolite previously proposed to have an antimicrobial effect.", "Here we show that itaconic acid inhibits the growth of bacteria expressing isocitrate lyase, such as Salmonella enterica and Mycobacterium tuberculosis.", " immune defense " ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/23610393", "http://www.ncbi.nlm.nih.gov/pubmed/25209111", "http://www.ncbi.nlm.nih.gov/pubmed/25064235" ]

[ { "p": "http://www.w3.org/2004/02/skos/core#narrower", "s": "http://linkedlifedata.com/resource/umls/id/C0064110", "o": "http://linkedlifedata.com/resource/umls/id/C0951348" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A7819222", "o": "itaconic acid, copper salt" }, { "p": "http://linkedlifedata.com/resource/umls/prefMetaMap", "s": "http://linkedlifedata.com/resource/umls/id/C0064110", "o": "http://linkedlifedata.com/resource/umls/label/A0196938" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A0196938", "o": "itaconic acid" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A0204017", "o": "methylenesuccinic acid" }, { "p": "http://linkedlifedata.com/resource/umls/altMetaMap", "s": "http://linkedlifedata.com/resource/umls/id/C0064110", "o": "http://linkedlifedata.com/resource/umls/label/A0204017" }, { "p": "http://www.w3.org/2008/05/skos-xl#prefLabel", "s": "http://linkedlifedata.com/resource/umls/id/C0951348", "o": "http://linkedlifedata.com/resource/umls/label/A7819222" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A0204008", "o": "methylenebutanedioic acid" }, { "p": "http://www.w3.org/2008/05/skos-xl#prefLabel", "s": "http://linkedlifedata.com/resource/umls/id/C0064110", "o": "http://linkedlifedata.com/resource/umls/label/A0196938" }, { "p": "http://linkedlifedata.com/resource/umls/altMetaMap", "s": "http://linkedlifedata.com/resource/umls/id/C0064110", "o": "http://linkedlifedata.com/resource/umls/label/A0204008" }, { "p": "http://www.w3.org/2004/02/skos/core#narrower", "s": "http://linkedlifedata.com/resource/umls/id/C0064110", "o": "http://linkedlifedata.com/resource/umls/id/C0951349" }, { "p": "http://www.w3.org/2008/05/skos-xl#prefLabel", "s": "http://linkedlifedata.com/resource/umls/id/C0951349", "o": "http://linkedlifedata.com/resource/umls/label/A7819221" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A7819221", "o": "itaconic acid, calcium salt" } ]

[]

[ "No. Multiple lines of experimental evidence suggest that chromomethylases (CMTs) have been hitherto identified in plant genomes(Arabidopsis, maize, tomato). CMTs maintain CpNpG (N = A, T, C, or G) methylation and they are unique to the plant kingdom. The lack of CMT homologs in animal genomes could be explained based on the fact that, in contrast to plants, animals maintain primarily CG methylation. Therefore, the presence of CMTs is not required in the animal genomes." ]

[ "no" ]

[ "Many plant, animal, and fungal genomes contain cytosine DNA methylation in asymmetric sequence contexts (CpHpH, H = A, T, C).", "However, at the SUPERMAN locus, asymmetric methylation was only completely abolished in drm1 drm2 chromomethylase 3 (cmt3) triple mutant plants.", "Although neither the drm1 drm2 double mutants nor the cmt3 single mutants show morphological defects, drm1 drm2 cmt3 triple mutant plants show pleiotropic effects on plant development.", "Arabidopsis cmt3 chromomethylase mutations block non-CG methylation and silencing of an endogenous gene.", "The lack of CMT homologs in animal genomes could account for the observation that in contrast to plants, animals maintain primarily CG methylation.", "Dual binding of chromomethylase domains to H3K9me2-containing nucleosomes directs DNA methylation in plants.", "A role for CHROMOMETHYLASE3 in mediating transposon and euchromatin silencing during egg cell reprogramming in Arabidopsis.", "During embryogenesis there is a major switch from dependence upon maternally-deposited products to reliance on products of the zygotic genome.", "Expression analysis of eight putative tomato DNA methyltransferases encoding genes showed that one chromomethylase (CMT) and two rearranged methyltransferases (DRMs) are preferentially expressed in the pericarp during fruit growth and could be involved in the locus-specific increase of methylation observed at this developmental phase in the pericarp.", "Natural variation for alleles under epigenetic control by the maize chromomethylase zmet2.", "Arabidopsis has two types of methyltransferases with demonstrated maintenance activity: MET1, which maintains CpG methylation and is homologous to mammalian DNMT1, and CHROMOMETHYLASE 3 (CMT3), which maintains CpNpG (N = A, T, C, or G) methylation and is unique to the plant kingdom.", "Maize chromomethylase Zea methyltransferase2 is required for CpNpG methylation.", "A cytosine DNA methyltransferase containing a chromodomain, Zea methyltransferase2 (Zmet2), was cloned from maize. The sequence of ZMET2 is similar to that of the Arabidopsis chromomethylases CMT1 and CMT3, with C-terminal motifs characteristic of eukaryotic and prokaryotic DNA methyltransferases.", "We have detected a chromodomain embedded within the catalytic region of a predicted Arabidopsis DNA methyltransferase that is diverged from other eukaryotic enzymes. The 791 residue \"chromomethylase\" (CMT1) is encoded by a floral transcript that is spliced from 20 exons and is present at only approximately 1/10(-7) of total mRNA." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/11487702", "http://www.ncbi.nlm.nih.gov/pubmed/20505370", "http://www.ncbi.nlm.nih.gov/pubmed/17660570", "http://www.ncbi.nlm.nih.gov/pubmed/11459824", "http://www.ncbi.nlm.nih.gov/pubmed/12740729", "http://www.ncbi.nlm.nih.gov/pubmed/23021223", "http://www.ncbi.nlm.nih.gov/pubmed/9584105", "http://www.ncbi.nlm.nih.gov/pubmed/18488247", "http://www.ncbi.nlm.nih.gov/pubmed/12121623", "http://www.ncbi.nlm.nih.gov/pubmed/12151602" ]

[ { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_4F3634393937006", "o": "Chromomethylase" }, { "p": "http://purl.uniprot.org/core/submittedName", "s": "http://purl.uniprot.org/uniprot/O64997", "o": "http://linkedlifedata.com/resource/#_4F3634393937006" }, { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#subject", "s": "http://linkedlifedata.com/resource/#_4F3634393937007", "o": "http://linkedlifedata.com/resource/#_4F3634393937006" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_423147594832004", "o": "Chromomethylase" }, { "p": "http://purl.uniprot.org/core/submittedName", "s": "http://purl.uniprot.org/uniprot/B1GYH2", "o": "http://linkedlifedata.com/resource/#_423147594832004" }, { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#subject", "s": "http://linkedlifedata.com/resource/#_423147594832005", "o": "http://linkedlifedata.com/resource/#_423147594832004" }, { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#type", "s": "http://linkedlifedata.com/resource/#_423147594832004", "o": "http://purl.uniprot.org/core/Structured_Name" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_423147594831006", "o": "Chromomethylase" }, { "p": "http://purl.uniprot.org/core/submittedName", "s": "http://purl.uniprot.org/uniprot/B1GYH1", "o": "http://linkedlifedata.com/resource/#_423147594831006" }, { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#subject", "s": "http://linkedlifedata.com/resource/#_423147594831007", "o": "http://linkedlifedata.com/resource/#_423147594831006" }, { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#type", "s": "http://linkedlifedata.com/resource/#_423147594831006", "o": "http://purl.uniprot.org/core/Structured_Name" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_42314759483300E", "o": "Chromomethylase" }, { "p": "http://purl.uniprot.org/core/submittedName", "s": "http://purl.uniprot.org/uniprot/B1GYH3", "o": "http://linkedlifedata.com/resource/#_42314759483300E" }, { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#subject", "s": "http://linkedlifedata.com/resource/#_42314759483300F", "o": "http://linkedlifedata.com/resource/#_42314759483300E" }, { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#type", "s": "http://linkedlifedata.com/resource/#_42314759483300E", "o": "http://purl.uniprot.org/core/Structured_Name" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_4F3634393935004", "o": "Chromomethylase" }, { "p": "http://purl.uniprot.org/core/submittedName", "s": "http://purl.uniprot.org/uniprot/O64995", "o": "http://linkedlifedata.com/resource/#_4F3634393935004" }, { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#subject", "s": "http://linkedlifedata.com/resource/#_4F3634393935005", "o": "http://linkedlifedata.com/resource/#_4F3634393935004" }, { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#type", "s": "http://linkedlifedata.com/resource/#_4F3634393935004", "o": "http://purl.uniprot.org/core/Structured_Name" }, { "p": "http://linkedlifedata.com/resource/umls/prefMetaMap", "s": "http://linkedlifedata.com/resource/umls/id/C0676094", "o": "http://linkedlifedata.com/resource/umls/label/A1361869" }, { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#type", "s": "http://linkedlifedata.com/resource/umls/label/A1361869", "o": "http://www.w3.org/2008/05/skos-xl#Label" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A1361869", "o": "C112810" }, { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A1361869", "o": "MeSH" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A1361869", "o": "chromomethylase" }, { "p": "http://www.w3.org/2008/05/skos-xl#prefLabel", "s": "http://linkedlifedata.com/resource/umls/id/C0676094", "o": "http://linkedlifedata.com/resource/umls/label/A1361869" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_4F343931343400F", "o": "Chromomethylase" }, { "p": "http://purl.uniprot.org/core/submittedName", "s": "http://purl.uniprot.org/uniprot/O49144", "o": "http://linkedlifedata.com/resource/#_4F343931343400F" }, { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#subject", "s": "http://linkedlifedata.com/resource/#_4F34393134340010", "o": "http://linkedlifedata.com/resource/#_4F343931343400F" }, { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#type", "s": "http://linkedlifedata.com/resource/#_4F343931343400F", "o": "http://purl.uniprot.org/core/Structured_Name" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_4F353030333700F", "o": "Chromomethylase" }, { "p": "http://purl.uniprot.org/core/submittedName", "s": "http://purl.uniprot.org/uniprot/O50037", "o": "http://linkedlifedata.com/resource/#_4F353030333700F" }, { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#subject", "s": "http://linkedlifedata.com/resource/#_4F35303033370010", "o": "http://linkedlifedata.com/resource/#_4F353030333700F" }, { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#type", "s": "http://linkedlifedata.com/resource/#_4F353030333700F", "o": "http://purl.uniprot.org/core/Structured_Name" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_4F3634393936005", "o": "Chromomethylase" }, { "p": "http://purl.uniprot.org/core/submittedName", "s": "http://purl.uniprot.org/uniprot/O64996", "o": "http://linkedlifedata.com/resource/#_4F3634393936005" }, { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#subject", "s": "http://linkedlifedata.com/resource/#_4F3634393936006", "o": "http://linkedlifedata.com/resource/#_4F3634393936005" }, { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#type", "s": "http://linkedlifedata.com/resource/#_4F3634393936005", "o": "http://purl.uniprot.org/core/Structured_Name" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_513057534338006", "o": "Chromomethylase" }, { "p": "http://purl.uniprot.org/core/submittedName", "s": "http://purl.uniprot.org/uniprot/Q0WSC8", "o": "http://linkedlifedata.com/resource/#_513057534338006" }, { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#subject", "s": "http://linkedlifedata.com/resource/#_513057534338007", "o": "http://linkedlifedata.com/resource/#_513057534338006" }, { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#type", "s": "http://linkedlifedata.com/resource/#_513057534338006", "o": "http://purl.uniprot.org/core/Structured_Name" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://linkedlifedata.com/resource/pubmed/chemical/chromomethylase", "o": "chromomethylase" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_4F3634393934005", "o": "Chromomethylase" }, { "p": "http://purl.uniprot.org/core/submittedName", "s": "http://purl.uniprot.org/uniprot/O64994", "o": "http://linkedlifedata.com/resource/#_4F3634393934005" }, { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#subject", "s": "http://linkedlifedata.com/resource/#_4F3634393934006", "o": "http://linkedlifedata.com/resource/#_4F3634393934005" }, { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#type", "s": "http://linkedlifedata.com/resource/#_4F3634393934005", "o": "http://purl.uniprot.org/core/Structured_Name" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_42365A43513700D", "o": "Chromomethylase" }, { "p": "http://purl.uniprot.org/core/submittedName", "s": "http://purl.uniprot.org/uniprot/B6ZCQ7", "o": "http://linkedlifedata.com/resource/#_42365A43513700D" }, { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#subject", "s": "http://linkedlifedata.com/resource/#_42365A43513700E", "o": "http://linkedlifedata.com/resource/#_42365A43513700D" }, { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#type", "s": "http://linkedlifedata.com/resource/#_42365A43513700D", "o": "http://purl.uniprot.org/core/Structured_Name" } ]

[ "http://www.uniprot.org/uniprot/CMT3_ARATH", "http://www.uniprot.org/uniprot/CMT2_ARATH", "http://www.uniprot.org/uniprot/CMT1_ARATH" ]

[ "The genes associated with the X-linked and the autosomal dominant forms of Charcot-Marie-Tooth disease are GJB1, MPZ, INF2, DNM2, YARS, GNB4, NEFL, MFN2, LRSAM1, GDAP1, PMP22, LITAF, and EGR2. Identification of these genes has not only been important for patients and families, but also provided new information about disease pathogenesis." ]

[ "GJB1", "MPZ", "INF2", "DNM2", "YARS", "GNB4", "NEFL", "MFN2", "LRSAM1", "GDAP1", "PMP22", "LITAF", "EGR2" ]

[ " GJB1 is currently considered to be associated with X-linked DI-CMT, and MPZ, INF2, DNM2, YARS, GNB4, NEFL, and MFN2 are associated with autosomal DI-CMT. Moreover, GDAP1, KARS, and PLEKHG5 are associated with RI-CMT. Identification of these genes is not only important for patients and families but also provides new information about pathogenesis", "A novel mutation in LRSAM1 causes axonal Charcot-Marie-Tooth disease with dominant inheritance", "Charcot-Marie-Tooth disease (CMT) refers to a heterogeneous group of genetic motor and sensory neuropathies. According to the primary site of damage, a distinction is made between demyelinating and axonal forms (CMT1 and 2, respectively, when inherited as an autosomal dominant trait). Leucine-rich repeat and sterile alpha motif-containing protein 1 (LRSAM1) is a ubiquitin-protein ligase with a role in sorting internalised cell-surface receptor proteins. So far, mutations in the LRSAM1 gene have been shown to cause axonal CMT in three different families and can confer either dominant or recessive transmission of the disease", "We have identified a novel mutation in LRSAM1 in a small family with dominant axonal CMT", "Phenotypical features of the p.R120W mutation in the GDAP1 gene causing autosomal dominant Charcot-Marie-Tooth disease", "Mutations in the ganglioside-induced-differentiation-associated protein 1 gene (GDAP1) can cause Charcot-Marie-Tooth (CMT) disease with demyelinating (CMT4A) or axonal forms (CMT2K and ARCMT2K). Most of these mutations present a recessive inheritance, but few autosomal dominant GDAP1 mutations have also been reported", " Our findings highlight the relevance of dominantly transmitted p.R120W GDAP1 gene mutations which can cause an axonal CMT with a wide clinical profile", "A novel GDAP1 Q218E mutation in autosomal dominant Charcot-Marie-Tooth disease", "There have been very few reports of GDAP1 mutations in autosomal dominant (AD) CMT", "Here, we report an AD CMT family with a novel Q218E mutation in the GDAP1 gene", "CMT type 1 (CMT1; MIM 118200) is a group of autosomal dominant-inherited demyelinating neuropathies with a disease onset at or after childhood. Five different subtypes have been identified based on different causative genes. Among them, CMT1A (MIM #118220) is most common and is usually associated with a duplication of a 1.5-Mb region on chromosome 17p11.2, which includes peripheral myelin protein 22 gene (PMP22; MIM *601097)", "Mutations in the NF-L gene (NEFL) cause autosomal dominant neuropathies that are classified either as axonal Charcot-Marie-Tooth (CMT) type 2E (CMT2E) or demyelinating CMT type 1F (CMT1F)", "Recently, mutations affecting different domains of dynamin-2 (DNM2) were associated alternatively with autosomal dominant centronuclear myopathy or dominant intermediate (demyelinating and axonal) Charcot-Marie-Tooth disease (CMT) type B", "Four genes (PMP22, MPZ, LITAF, and EGR2) have been described in the last 15 yr associated with AD CMTI and a further gene (NEFL), originally described as causing AD CMT2 can also cause AD CMT1 (by neurophysiological criteria)", "Mutations in the pleckstrin homology domain of dynamin 2 cause dominant intermediate Charcot-Marie-Tooth disease", "We refined the locus associated with DI-CMTB on chromosome 19p12-13.2 to 4.2 Mb in three unrelated families with CMT originating from Australia, Belgium and North America. After screening candidate genes, we identified unique mutations in dynamin 2 (DNM2) in all families", "Here, we report a large family showing characteristic phenotypes of Charcot-Marie-Tooth type 1A along with deafness in an autosomal dominant fashion. We detected a sequence variation (c.68C>G) co-segregating with the disease phenotype and leading to a T23R missense mutation in PMP22", "The authors recently mapped an autosomal dominant demyelinating form of CMT type 1 (CMT1C) to chromosome 16p13.1-p12.3", "The authors identified missense mutations (G112S, T115N, W116G) in the LITAFgene (lipopolysaccharide-induced tumor necrosis factor-alpha factor) in three CMT1C pedigrees", "We identified a novel neurofilament-light missense mutation (C64T) that causes the disease in a large Slovenian CMT2 family. This novel mutation shows complete co-segregation with the dominantly inherited CMT2 phenotype in our family", "Phenotypical features of the p.R120W mutation in the GDAP1 gene causing autosomal dominant Charcot-Marie-Tooth disease.", "Ganglioside-induced differentiation associated-protein 1 (GDAP1) mutations are commonly associated with autosomal recessive Charcot-Marie-Tooth (ARCMT) neuropathy; however, in rare instances, they also lead to autosomal dominant Charcot-Marie-Tooth (ADCMT).", "A novel GDAP1 Q218E mutation in autosomal dominant Charcot-Marie-Tooth disease.", "In this study, we aimed to elucidate the disease mechanisms in dominant intermediate Charcot-Marie-Tooth neuropathy type B and to find explanations for the tissue-specific defects that are associated with different DNM2 mutations in dominant intermediate Charcot-Marie-Tooth neuropathy type B versus autosomal dominant centronuclear myopathy.", "Mutations in dynamin 2 (DNM2) lead to dominant intermediate Charcot-Marie-Tooth neuropathy type B, while a different set of DNM2 mutations cause autosomal dominant centronuclear myopathy.", "A novel LRSAM1 mutation is associated with autosomal dominant axonal Charcot-Marie-Tooth disease", "Recently, mutations affecting different domains of dynamin-2 (DNM2) were associated alternatively with autosomal dominant centronuclear myopathy or dominant intermediate (demyelinating and axonal) Charcot-Marie-Tooth disease (CMT) type B.", "Mutations in the Dynamin 2 gene (DNM2) cause autosomal dominant centronuclear myopathy or autosomal dominant (AD) Charcot-Marie-Tooth (CMT) disease", "Mutations in the ganglioside-induced differentiation-associated protein 1 gene cause either autosomal recessive demyelinating Charcot-Marie-Tooth disease type 4A or autosomal recessive axonal Charcot-Marie-Tooth disease with vocal cord paresis", "A novel mutation in the GDAP1 gene is associated with autosomal recessive Charcot-Marie-Tooth disease in an Amish family", "Phenotypical features of a Moroccan family with autosomal recessive Charcot-Marie-Tooth disease associated with the S194X mutation in the GDAP1 gene", "Autosomal dominant Charcot-Marie-Tooth type-1A neuropathy (CMT1A) is a demyelinating peripheral nerve disorder that is commonly associated with a submicroscopic tandem DNA duplication of a 1.5-Mb region of 17p11.2p12 that contains the peripheral myelin gene PMP22. ", "OBJECTIVE: Ganglioside-induced differentiation associated-protein 1 (GDAP1) mutations are commonly associated with autosomal recessive Charcot-Marie-Tooth (ARCMT) neuropathy; however, in rare instances, they also lead to autosomal dominant Charcot-Marie-Tooth (ADCMT). ", "Mutations in the ganglioside-induced-differentiation-associated protein 1 gene (GDAP1) can cause Charcot-Marie-Tooth (CMT) disease with demyelinating (CMT4A) or axonal forms (CMT2K and ARCMT2K). ", "Mutations in the NEFL gene were recently reported as a cause for autosomal dominant Charcot-Marie-Tooth type 2E (CMT2E) linked to chromosome 8p21. ", "Mild functional differences of dynamin 2 mutations associated to centronuclear myopathy and Charcot-Marie Tooth peripheral neuropathy.", "Ganglioside-induced differentiation associated-protein 1 (GDAP1) mutations are commonly associated with autosomal recessive Charcot-Marie-Tooth (ARCMT) neuropathy; however, in rare instances, they also lead to autosomal dominant Charcot-Marie-Tooth (ADCMT).", "In this study, we aimed to elucidate the disease mechanisms in dominant intermediate Charcot-Marie-Tooth neuropathy type B and to find explanations for the tissue-specific defects that are associated with different DNM2 mutations in dominant intermediate Charcot-Marie-Tooth neuropathy type B versus autosomal dominant centronuclear myopathy. We used tissue derived from Dnm2-deficient mice to establish an appropriate peripheral nerve model and found that dominant intermediate Charcot-Marie-Tooth neuropathy type B-associated dynamin 2 mutants, but not autosomal dominant centronuclear myopathy mutants, impaired myelination.", " Mutations in dynamin 2 (DNM2) lead to dominant intermediate Charcot-Marie-Tooth neuropathy type B, while a different set of DNM2 mutations cause autosomal dominant centronuclear myopathy. In this study, we aimed to elucidate the disease mechanisms in dominant intermediate Charcot-Marie-Tooth neuropathy type B and to find explanations for the tissue-specific defects that are associated with different DNM2 mutations in dominant intermediate Charcot-Marie-Tooth neuropathy type B versus autosomal dominant centronuclear myopathy.", "We conclude that dynamin 2 mutations should be screened in the autosomal dominant Charcot-Marie-Tooth neuropathy families with intermediate or axonal NCV, and in patients with a classical mild to moderately severe Charcot-Marie-Tooth phenotype, especially when Charcot-Marie-Tooth is associated with neutropaenia or cataracts. .", "A novel LRSAM1 mutation is associated with autosomal dominant axonal Charcot-Marie-Tooth disease.", "We conclude that dynamin 2 mutations should be screened in the autosomal dominant Charcot-Marie-Tooth neuropathy families with intermediate or axonal NCV, and in patients with a classical mild to moderately severe Charcot-Marie-Tooth phenotype, especially when Charcot-Marie-Tooth is associated with neutropaenia or cataracts.", "In this study, we aimed to elucidate the disease mechanisms in dominant intermediate Charcot-Marie-Tooth neuropathy type B and to find explanations for the tissue-specific defects that are associated with different DNM2 mutations in dominant intermediate Charcot-Marie-Tooth neuropathy type B versus autosomal dominant centronuclear myopathy.", "Phenotypical features of the p.R120W mutation in the GDAP1 gene causing autosomal dominant Charcot-Marie-Tooth disease.", "Mutations in the ganglioside-induced-differentiation-associated protein 1 gene (GDAP1) can cause Charcot-Marie-Tooth (CMT) disease with demyelinating (CMT4A) or axonal forms (CMT2K and ARCMT2K).", "A wide range of phenotypes have been reported in autosomal recessive (AR) Charcot-Marie-Tooth disease (CMT) patients carrying mutations in the ganglioside-induced differentiation-associated protein 1 (GDAP1) gene, such as axonal, demyelinating, and intermediate forms of AR CMT.", "A severe recessive and a mild dominant form of Charcot-Marie-Tooth disease associated with a newly identified Glu222Lys GDAP1 gene mutation.", "A novel GDAP1 Q218E mutation in autosomal dominant Charcot-Marie-Tooth disease.", "A novel LRSAM1 mutation is associated with autosomal dominant axonal Charcot-Marie-Tooth disease." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/25337607", "http://www.ncbi.nlm.nih.gov/pubmed/14561495", "http://www.ncbi.nlm.nih.gov/pubmed/12707075", "http://www.ncbi.nlm.nih.gov/pubmed/16775366", "http://www.ncbi.nlm.nih.gov/pubmed/24894446", "http://www.ncbi.nlm.nih.gov/pubmed/15099592", "http://www.ncbi.nlm.nih.gov/pubmed/12481988", "http://www.ncbi.nlm.nih.gov/pubmed/18492089", "http://www.ncbi.nlm.nih.gov/pubmed/17636067", "http://www.ncbi.nlm.nih.gov/pubmed/22451505", "http://www.ncbi.nlm.nih.gov/pubmed/21753178", "http://www.ncbi.nlm.nih.gov/pubmed/12566280", "http://www.ncbi.nlm.nih.gov/pubmed/25326399", "http://www.ncbi.nlm.nih.gov/pubmed/18231710", "http://www.ncbi.nlm.nih.gov/pubmed/18975529", "http://www.ncbi.nlm.nih.gov/pubmed/12525712", "http://www.ncbi.nlm.nih.gov/pubmed/8655146", "http://www.ncbi.nlm.nih.gov/pubmed/22091729", "http://www.ncbi.nlm.nih.gov/pubmed/17052987", "http://www.ncbi.nlm.nih.gov/pubmed/19502294", "http://www.ncbi.nlm.nih.gov/pubmed/21199105", "http://www.ncbi.nlm.nih.gov/pubmed/22781092", "http://www.ncbi.nlm.nih.gov/pubmed/22096584", "http://www.ncbi.nlm.nih.gov/pubmed/15731758" ]

[]

[]

[ "Transcriptional activation of the IFN beta gene in response to virus infection requires the assembly of an enhanceosome, consisting of the transcriptional activators NF-kappa B, IRF1, ATF2/c-Jun, and the architectural protein HMG I(Y). Transcriptional activation of the human interferon-beta (IFN-beta) gene by virus infection requires the assembly of a higher order nucleoprotein complex, the enhanceosome, which consists of the transcriptional activators NF-kappa B (p50/p65), ATF-2/c-jun, IRF-3 and IRF-7, architectural protein HMGI(Y), and the coactivators p300 and CBP. ", "Transcriptional activation of the human interferon-beta (IFN-beta) gene by virus infection requires the assembly of a higher order nucleoprotein complex, the enhanceosome, which consists of the transcriptional activators NF-kappa B (p50/p65), ATF-2/c-jun, IRF-3 and IRF-7, architectural protein HMGI(Y), and the coactivators p300 and CBP. A functional interferon-beta gene enhanceosome was assembled in vitro using the purified recombinant transcriptional activator proteins ATF2/c-JUN, IRF1, and p50/p65 of NF-kappa B. However, HMG I(Y) plays an essential role in the assembly and function of the IFN beta gene enhanceosome." ]

[ "NF-kappa B (p50/p65)", "ATF-2", "c-jun", "IRF-3", "IRF-7", "IRF-1" ]

[ "The dimer formed by the ATF-2 and c-Jun transcription factors is one of the main components of the human interferon-beta enhanceosome.", "The induction of IFN transcription resulted from the activation of the components of the IFN-beta enhanceosome, i.e. IFN regulatory factor (IRF) 3, nuclear factor (NF)-kappaB, activating transcription factor (ATF)-2 and c-Jun.", "Transcriptional activation of the interferon-beta (IFN-beta) gene requires assembly of an enhanceosome containing the transcription factors ATF-2/c-Jun, IRF-3/IRF-7, NF-kappaB and HMGI(Y). These factors cooperatively bind a composite DNA site and activate expression of the IFN-beta gene.", "Here we report that within the IFN-beta enhanceosome the ATF-2-c-jun heterodimer binds in a specific orientation, which is required for assembly of a complex between ATF-2-c-jun and interferon regulatory factor 3 (IRF-3).", " Here, we identified a small molecule that induces the assembly of the interferon-beta (IFN-beta) enhanceosome by stimulating all the enhancer-binding activator proteins: ATF2/c-JUN, IRF3, and p50/p65 of NF-kappaB.", "Transcriptional activation of the virus inducible enhancer of the human interferon-beta (IFN-beta) gene in response to virus infection requires the assembly of an enhanceosome, consisting of the transcriptional activators NF-kappaB, ATF-2/c-Jun, IRFs and the architectural protein of the mammalian high mobility group I(Y) [HMG I(Y)].", "Here, we demonstrate that the first step in enhanceosome assembly, i.e. HMG I(Y)-dependent recruitment of NF-kappaB and ATF-2/c-Jun to the enhancer, is facilitated by discrete regions of HMG I and is mediated by allosteric changes induced in the DNA by HMG I(Y) and not by protein-protein interactions between HMG I(Y) and these proteins. However, we show that completion of the enhanceosome assembly process requires protein-protein interactions between HMG I(Y) and the activators.", "Transcriptional activation of the human interferon-beta (IFN-beta) gene by virus infection requires the assembly of a higher order nucleoprotein complex, the enhanceosome, which consists of the transcriptional activators NF-kappa B (p50/p65), ATF-2/c-jun, IRF-3 and IRF-7, architectural protein HMGI(Y), and the coactivators p300 and CBP. ", "The transcriptional coactivators CBP and P/CAF are required for activation of transcription from the IFN beta enhanceosome. We show that CBP and P/CAF acetylate HMG I(Y), the essential architectural component required for enhanceosome assembly, at distinct lysine residues, causing distinct effects on transcription.", "The transcriptional activity of an in vitro assembled human interferon-beta gene enhanceosome is highly synergistic. This synergy requires five distinct transcriptional activator proteins (ATF2/c-JUN, interferon regulatory factor 1, and p50/p65 of NF-kappaB), the high mobility group protein HMG I(Y), and the correct alignment of protein-binding sites on the face of the DNA double helix.", "In addition, we provide evidence that recruitment of the holoenzyme by the enhanceosome is due, at least in part, to interactions between the enhanceosome and the transcriptional coactivator CREB, cAMP responsive element binding protein (CBP). ", "Transcriptional activation of the IFN beta gene in response to virus infection requires the assembly of an enhanceosome, consisting of the transcriptional activators NF-kappa B, IRF1, ATF2/c-Jun, and the architectural protein HMG I(Y).", "Transcriptional synergy requires recruitment of the CBP/p300 coactivator to the enhanceosome, via a new activating surface assembled from the novel p65 domain and the activation domains of all of the activators.", "A functional interferon-beta gene enhanceosome was assembled in vitro using the purified recombinant transcriptional activator proteins ATF2/c-JUN, IRF1, and p50/p65 of NF-kappa B. Maximal levels of transcriptional synergy between these activators required the specific interactions with the architectural protein HMG I(Y) and the correct helical phasing of the binding sites of these proteins on the DNA helix.", "We present evidence that transcriptional activation of the human interferon-beta (IFN beta) gene requires the assembly of a higher order transcription enhancer complex (enhanceosome). This multicomponent complex includes at least three distinct transcription factors and the high mobility group protein HMG I(Y).", "Thus, HMG I(Y) plays an essential role in the assembly and function of the IFN beta gene enhanceosome.", "Transcriptional activation of the interferon-beta (IFN-beta) gene requires assembly of an enhanceosome containing the transcription factors ATF-2/c-Jun, IRF-3/IRF-7, NF-kappaB and HMGI(Y).", "A functional interferon-beta gene enhanceosome was assembled in vitro using the purified recombinant transcriptional activator proteins ATF2/c-JUN, IRF1, and p50/p65 of NF-kappa B", "Transcriptional activation of the human interferon-beta (IFN-beta) gene by virus infection requires the assembly of a higher order nucleoprotein complex, the enhanceosome, which consists of the transcriptional activators NF-kappa B (p50/p65), ATF-2/c-jun, IRF-3 and IRF-7, architectural protein HMGI(Y), and the coactivators p300 and CBP", "Transcriptional activation of the IFN beta gene in response to virus infection requires the assembly of an enhanceosome, consisting of the transcriptional activators NF-kappa B, IRF1, ATF2/c-Jun, and the architectural protein HMG I(Y)" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/10747925", "http://www.ncbi.nlm.nih.gov/pubmed/19944700", "http://www.ncbi.nlm.nih.gov/pubmed/15510218", "http://www.ncbi.nlm.nih.gov/pubmed/10024886", "http://www.ncbi.nlm.nih.gov/pubmed/9770462", "http://www.ncbi.nlm.nih.gov/pubmed/8548797", "http://www.ncbi.nlm.nih.gov/pubmed/10357819", "http://www.ncbi.nlm.nih.gov/pubmed/9809067", "http://www.ncbi.nlm.nih.gov/pubmed/9659924", "http://www.ncbi.nlm.nih.gov/pubmed/10848607", "http://www.ncbi.nlm.nih.gov/pubmed/18420790", "http://www.ncbi.nlm.nih.gov/pubmed/9659909" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016899", "http://www.uniprot.org/uniprot/IFN_ANAPL", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0034206", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D014157", "http://www.biosemantics.org/jochem#4250284" ]

[ "BNP and fT3 are independently associated in severely compromised HF patients.\nNT-pro-BNP was significantly associated with low-T3 syndrome in cardiac patients.\nHigher NT-pro BNP concentrations are related to lower total T3 concentrations in cardiac patients" ]

[ "yes" ]

[ "BNP and fT3 are independently associated with exercise capacity in severely compromised HF patients.", "fter adjustment for known confounders, NT-pro-BNP was significantly associated with fT3 and low-T3 syndrome. fT3 (HR 0.58, 95%CI 0.34-0.98) and low-T3 syndrome (HR 3.0, 95%CI 1.4-6.3) were predictive for mortality after adjustment for NT-pro-BNP levels and other cardiovascular prognostic variables.", "fT3 and low-T3 syndrome are significantly related to NT-pro-BNP in patients with cardiovascular disease, but are predictors of mortality independently of NT-pro-BNP and other known cardiovascular risk parameters.", "Higher NT-pro BNP concentrations were related to lower total T3 concentrations (r = -0.294, p = 0.011) and to higher reverse T3 concentrations (r = 0.353, p = 0.002)" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/14678288", "http://www.ncbi.nlm.nih.gov/pubmed/22870736", "http://www.ncbi.nlm.nih.gov/pubmed/17375888", "http://www.ncbi.nlm.nih.gov/pubmed/16649727", "http://www.ncbi.nlm.nih.gov/pubmed/18620103", "http://www.ncbi.nlm.nih.gov/pubmed/18729306", "http://www.ncbi.nlm.nih.gov/pubmed/17646607", "http://www.ncbi.nlm.nih.gov/pubmed/12655635", "http://www.ncbi.nlm.nih.gov/pubmed/12578873", "http://www.ncbi.nlm.nih.gov/pubmed/8345811", "http://www.ncbi.nlm.nih.gov/pubmed/20492497", "http://www.ncbi.nlm.nih.gov/pubmed/18949097", "http://www.ncbi.nlm.nih.gov/pubmed/19423177", "http://www.ncbi.nlm.nih.gov/pubmed/16952785", "http://www.ncbi.nlm.nih.gov/pubmed/19181292", "http://www.ncbi.nlm.nih.gov/pubmed/17635576", "http://www.ncbi.nlm.nih.gov/pubmed/18073483", "http://www.ncbi.nlm.nih.gov/pubmed/20888651", "http://www.ncbi.nlm.nih.gov/pubmed/19221174", "http://www.ncbi.nlm.nih.gov/pubmed/19778808" ]

[]

[ "http://www.uniprot.org/uniprot/ANFB_OREMO", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005067", "http://www.disease-ontology.org/api/metadata/DOID:2856", "http://www.disease-ontology.org/api/metadata/DOID:1287", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D006331", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011988", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D020097" ]

[ "Neighbourhood Consistent PC (NCPC) algorithms, MMDiff and cosmo." ]

[ "Neighbourhood Consistent PC (NCPC) algorithms", "MMDiff", "cosmo", "dPattern", "TFBS" ]

[ "Clustered occurrence of multiple TFs at genomic sites may arise from chromatin accessibility and local cooperation between TFs, or binding sites may simply appear clustered if the profiles are generated from diverse cell populations. Overlaps in TF binding profiles may also result from measurements taken at closely related time intervals. It is thus of great interest to distinguish TFs that directly regulate gene expression from those that are indirectly associated with gene expression. Graphical models, in particular Bayesian networks, provide a powerful mathematical framework to infer different types of dependencies. However, existing methods do not perform well when the features (here: TF binding profiles) are highly correlated, when their association with the biological outcome is weak, and when the sample size is small. Here, we develop a novel computational method, the Neighbourhood Consistent PC (NCPC) algorithms, which deal with these scenarios much more effectively than existing methods do. We further present a novel graphical representation, the Direct Dependence Graph (DDGraph), to better display the complex interactions among variables. NCPC and DDGraph can also be applied to other problems involving highly correlated biological features. Both methods are implemented in the R package ddgraph, available as part of Bioconductor", "Here, we present MMDiff, a robust, broadly applicable method for detecting differences between sequence count data sets. Based on quantifying shape changes in signal profiles, it overcomes challenges imposed by the highly structured nature of the data and the paucity of replicates", "Supervised detection of conserved motifs in DNA sequences with cosmo", "We here introduce an algorithm, called cosmo, that allows this search to be supervised by specifying a set of constraints that the position weight matrix of the unknown motif must satisfy. Such constraints may be formulated, for example, on the basis of prior knowledge about the structure of the transcription factor in question. The algorithm is based on the same two-component multinomial mixture model used by MEME, with stronger reliance, however, on the likelihood principle instead of more ad-hoc criteria like the E-value", "dPattern: transcription factor binding site (TFBS) discovery in human genome using a discriminative pattern analysis.", "TFBS: Computational framework for transcription factor binding site analysis." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/23144600", "http://www.ncbi.nlm.nih.gov/pubmed/17402923", "http://www.ncbi.nlm.nih.gov/pubmed/17550915", "http://www.ncbi.nlm.nih.gov/pubmed/24267901", "http://www.ncbi.nlm.nih.gov/pubmed/12176838" ]

[]

[ "http://amigo.geneontology.org/amigo/term/GO:0008134", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001665" ]

[ "The Simpson grading system was used to assess the extent of surgical resection of meningioma." ]

[ "meningioma" ]

[ "The impact of age (≤ 70 vs.>70 years), sex, tumor diameter (<6 vs. ≥ 6 cm), pre- and postoperative KPS (<80 vs. ≥ 80), Simpson grade (I-II vs. III-IV), and World Health Organization (WHO) histologic grade (I vs. II-III) on survival was assessed. Kaplan-Meier survival curves were plotted and differences in survival between groups of patients were compared. A multivariate analysis adjusted for age, pre- and postoperative KPS, Simpson grade, tumor diameter, and WHO histologic grade also was performed.RESULTS: The fronto-orbito-basal approach (n = 22) allowed a significantly greater percentage of Simpson I-II removals than the bifrontal (n = 70) and pterional approach (n = 21) (P = 0.0354 and P = 0.0485, respectively). ", "Simpson Grade I-III Resection of Spinal Atypical (World Health Organization Grade II) Meningiomas is Associated With Symptom Resolution and Low Recurrence.", "Simpson grade I, II, III, and IV resection were achieved in 3 (15%), 13 (65%), 2 (10%), and 2 (10%) tumors, respectively. One patient that underwent Simpson grade III resection received adjuvant radiation therapy. After Simpson grade I-III or gross total resection, no tumors recurred (0%; confidence interval, 0%-17.6%). After Simpson grade IV resection, 1 tumor recurred (50%; confidence interval, 1.3%-98.7%). ", " The Simpson grading system was used to assess the extent of surgical resection.", "Simpson grade: an opportunity to reassess the need for complete resection of meningiomas.", "BACKGROUND: The relevance of the Simpson grading system as a predictor of meningioma progression or recurrence in modern neurosurgical practice has recently been called into question. The aim of our study was to compare the risk of progression/recurrence of tumours that had been treated with different Simpson grade resections in a contemporary population of benign (WHO grade I) meningioma patients.", "RESULTS: The three-year progression/recurrence-free survival rates for patients receiving Simpson grade 1, 2 or 4 resections were 95 %, 87 % and 67 %, respectively. Simpson grade 4 resections progressed/recurred at a significantly greater rate than Simpson grade 1 resections (hazard ratio [HR] = 3.26, P = 0.04), whereas Simpson grade 2 resections did not progress/recur at a significantly greater rate than Simpson grade 1 resections (HR = 1.78, P = 0.29).", "Effect of dural detachment on long-term tumor control for meningiomas treated using Simpson grade IV resection.", "The Simpson grading system classifies incomplete resections into a single category, namely Simpson Grade IV, with wide variations in the volume and location of residual tumors, making it complicated to evaluate the achievement of surgical goals and predict the prognosis of these tumors. Authors of the present study investigated the factors related to necessity of retreatment and tried to identify any surgical nuances achievable with the aid of modern neurosurgical techniques for meningiomas treated using Simpson Grade IV resection.METHODS: This retrospective analysis included patients with WHO Grade I meningiomas treated using Simpson Grade IV resection as the initial therapy at the University of Tokyo Hospital between January 1995 and April 2010. ", "Stereotactic radiosurgery provides equivalent tumor control to Simpson Grade 1 resection for patients with small- to medium-size meningiomas.", "Multivariate analysis revealed that no dural detachment (hazard ratio [HR]6.42, 95% CI 1.41-45.0; p = 0.02) and skull base location (HR 11.6, 95% CI 2.18-218; p = 0.002) were independent risk factors for the necessity of early retreatment, whereas postresection tumor volume of 4 cm(3) or more was not a statistically significant risk factor.CONCLUSIONS: Compared with Simpson Grade I, II, and III resections, Simpson Grade IV resection includes highly heterogeneous tumors in terms of resection rate and location of the residual mass. Despite the difficulty in analyzing such diverse data, these results draw attention to the favorable effect of dural detachment (instead of maximizing the resection rate) on long-term tumor control. Surgical strategy with an emphasis on detaching the tumor from the affected dura might be another important option in resection of high-risk meningiomas not amenable to gross-total resection.", "The relevance of Simpson Grade I and II resection in modern neurosurgical treatment of World Health Organization Grade I meningiomas.", "Surgery for convexity meningioma: Simpson Grade I resection as the goal: clinical article.", "However, for skull base meningiomas, in which mostly Simpson Grade II resection is achieved, the use of this classification should be further validated. " ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/12605979", "http://www.ncbi.nlm.nih.gov/pubmed/25774702", "http://www.ncbi.nlm.nih.gov/pubmed/24965072", "http://www.ncbi.nlm.nih.gov/pubmed/25464274", "http://www.ncbi.nlm.nih.gov/pubmed/22839654", "http://www.ncbi.nlm.nih.gov/pubmed/20380529", "http://www.ncbi.nlm.nih.gov/pubmed/23061394", "http://www.ncbi.nlm.nih.gov/pubmed/24053497", "http://www.ncbi.nlm.nih.gov/pubmed/24193889" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001932" ]

[ "centrosome" ]

[ "centrosome" ]

[ "CEP family protein is the active component of centrosome", "Cep135/Bld10 is a conserved centriolar protein required for the formation of the central cartwheel, an early intermediate in centriole assembly.", "Thus, in flies, Cep135/Bld10 is not essential for cartwheel assembly or for establishing the ninefold symmetry of centrioles; rather, it appears to stabilize the connection between inner and outer centriole components.", "Cep135 is a 135-kDa, coiled-coil centrosome protein important for microtubule organization in mammalian cells", "135 kDa centrosomal protein (CEP135)", "In the present study, we investigated a novel interaction between CEP135 and C-NAP1, two core centriolar proteins.", "Drosophila Bld10, the ortholog of Chlamydomonas reinhardtii Bld10p and human Cep135, is a ubiquitous centriolar protein that also localizes to the spermatid basal body. M", "BLD10/CEP135 is a microtubule-associated protein that controls the formation of the flagellum central microtubule pair.", "We found an evolutionarily cohesive and ancestral module, which we term UNIMOD and is defined by three components (SAS6, SAS4/CPAP and BLD10/CEP135), that correlates with the occurrence of CBBs.", "pericentriolar material proteins including pericentrin and CEP135.", "hereas Cep135 and CPAP formed a core structure within the proximal lumen of both parental and nascent centrioles", ". Centrosome components, including γ-tubulin and Cep135,", "suggesting that Cep135 is a structural component of the centrosome." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/20392737", "http://www.ncbi.nlm.nih.gov/pubmed/22898782", "http://www.ncbi.nlm.nih.gov/pubmed/23456457", "http://www.ncbi.nlm.nih.gov/pubmed/17681131", "http://www.ncbi.nlm.nih.gov/pubmed/22261722", "http://www.ncbi.nlm.nih.gov/pubmed/23213374", "http://www.ncbi.nlm.nih.gov/pubmed/19321663", "http://www.ncbi.nlm.nih.gov/pubmed/14983524", "http://www.ncbi.nlm.nih.gov/pubmed/22976301", "http://www.ncbi.nlm.nih.gov/pubmed/21766470", "http://www.ncbi.nlm.nih.gov/pubmed/18851962", "http://www.ncbi.nlm.nih.gov/pubmed/23115304", "http://www.ncbi.nlm.nih.gov/pubmed/10842375", "http://www.ncbi.nlm.nih.gov/pubmed/19454482", "http://www.ncbi.nlm.nih.gov/pubmed/22521416", "http://www.ncbi.nlm.nih.gov/pubmed/11781336", "http://www.ncbi.nlm.nih.gov/pubmed/19293139", "http://www.ncbi.nlm.nih.gov/pubmed/16240430" ]

[]

[ "http://www.uniprot.org/uniprot/CP135_HUMAN" ]

[ "Delayed enhancement is documented in almost 30% of patients with non-ischemic dilated cardiomyopathy and its pattern is characterized by mid-wall, patchy or diffuse location." ]

[ "yes" ]

[ "Myocardial fibrosis was present in 30% of patients, the majority of which was mid-myocardial (63%). ", " DCM patients frequently have myocardial fibrosis detected on CE-CMR, the majority of which is mid-myocardial.", "Fifty (40%) patients showed myocardial DE, representing 12±7% of LV mass.", "one case was dilated cardiomyopathy, in which the delayed enhancement was diffuse small midwall spots ", "In the dilated cardiomyopathy group, only seven (29%) patients showed delayed enhancement and its pattern was characterized by mid-wall, patchy or diffuse location.", "Patterns of delayed enhancement are different in dilated cardiomyopathy and ischemic cardiomyopathy, reflecting the presence of scarring or various degrees of fibrosis in left ventricular myocardium. The presence of subendocardial or transmural delayed enhancement at contrast-enhanced cardiovascular magnetic resonance allowed distinction between dilated cardiomyopathy and ischemic cardiomyopathy with high sensitivity (88%) and specificity (100%)." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/17885521", "http://www.ncbi.nlm.nih.gov/pubmed/21176853", "http://www.ncbi.nlm.nih.gov/pubmed/22875171", "http://www.ncbi.nlm.nih.gov/pubmed/23021326", "http://www.ncbi.nlm.nih.gov/pubmed/17131077", "http://www.ncbi.nlm.nih.gov/pubmed/19185371", "http://www.ncbi.nlm.nih.gov/pubmed/19317068", "http://www.ncbi.nlm.nih.gov/pubmed/23422782", "http://www.ncbi.nlm.nih.gov/pubmed/20118568", "http://www.ncbi.nlm.nih.gov/pubmed/17602984", "http://www.ncbi.nlm.nih.gov/pubmed/22552168", "http://www.ncbi.nlm.nih.gov/pubmed/21234292", "http://www.ncbi.nlm.nih.gov/pubmed/20149594", "http://www.ncbi.nlm.nih.gov/pubmed/24315973" ]

[]

[ "http://www.disease-ontology.org/api/metadata/DOID:0050700", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009682", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D008279", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009202", "http://www.disease-ontology.org/api/metadata/DOID:12930", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D002311" ]

[ "Varespladib is a secretory phospholipase A2 (sPLA2) inhibitor. It was tested in patients with acute coronary syndrome." ]

[ "secretory phospholipase A2" ]

[ "The VISTA-16 trial of varespladib, a secretory phospholipase A2 (sPLA2) inhibitor, in patients with an acute coronary syndrome was terminated prematurely owing to futility and a signal towards harm.", "Large-scale Phase III trials are now underway with agents that lead to marked reductions in IL-6 and C-reactive protein (such as canakinumab and methotrexate) as well as with agents that impact on diverse non-IL-6-dependent pathways (such as varespladib and darapladib). ", "The sPLA2 inhibitor varespladib has favorable effects on lipid and inflammatory markers; however, its effect on cardiovascular outcomes is unknown.OBJECTIVE: To determine the effects of sPLA2 inhibition with varespladib on cardiovascular outcomes.", "The sPLA2 inhibition with varespladib may be harmful and is not a useful strategy to reduce adverse cardiovascular outcomes after ACS.", "The potential pro-atherogenic role of PLA(2) led to the development of two small molecules, varespladib, a reversible sPLA(2) inhibitor, and darapladib, a selective Lp-PLA(2) inhibitor. ", "In the present article, the enzymatic properties and the involvement of sPLA(2) and Lp-PLA(2) in atherogenesis are reviewed, with a focus on the results of experimental studies and clinical studies with both varespladib and darapladib inhibitors.", "OBJECTIVE: Several secreted phospholipases A2 (sPLA2s), including group IIA, III, V, and X, have been linked to the development of atherosclerosis, which led to the clinical testing of A-002 (varespladib), a broad sPLA2 inhibitor for the treatment of coronary artery disease. ", "Varespladib was able to inhibit sPLA2 in the types of neonatal lung injury investigated. sPLA2 activity was reduced in hyaline membrane disease (P &lt; .0001), infections (P = .003), and meconium aspiration (P = .04) using 40 µM varespladib; 10 µM was able to lower enzyme activity (P = .001), with an IC(50) of 87 µM", "Varespladib methyl is a prodrug that is rapidly metabolized to varespladib, and both compounds are able to potently inhibit the enzymes of the human secretory phospholipase groups IIa, V and X, which play a pivotal role in atherosclerotic disease and inflammation", "The sPLA2 inhibitor varespladib has favorable effects on lipid and inflammatory markers; however, its effect on cardiovascular outcomes is unknown.OBJECTIVE: To determine the effects of sPLA2 inhibition with varespladib on cardiovascular outcomes.DESIGN, SETTING, AND PARTICIPANTS: A double-blind, randomized, multicenter trial at 362 academic and community hospitals in Europe, Australia, New Zealand, India, and North America of 5145 patients randomized within 96 hours of presentation of an acute coronary syndrome (ACS) to either varespladib (n = 2572) or placebo (n = 2573) with enrollment between June 1, 2010, and March 7, 2012 (study termination on March 9, 2012).INTERVENTIONS: Participants were randomized to receive varespladib (500 mg) or placebo daily for 16 weeks, in addition to atorvastatin and other established therapies.MAIN OUTCOMES AND MEASURES: The primary efficacy measure was a composite of cardiovascular mortality, nonfatal myocardial infarction (MI), nonfatal stroke, or unstable angina with evidence of ischemia requiring hospitalization at 16 weeks. ", "The composite secondary end point of cardiovascular mortality, MI, and stroke was observed in 107 patients (4.6%) in the varespladib group and 79 patients (3.8%) in the placebo group (HR, 1.36; 95% CI, 1.02-1.82; P = .04).CONCLUSIONS AND RELEVANCE: In patients with recent ACS, varespladib did not reduce the risk of recurrent cardiovascular events and significantly increased the risk of MI. The sPLA2 inhibition with varespladib may be harmful and is not a useful strategy to reduce adverse cardiovascular outcomes after ACS.TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01130246.", "The central hypothesis of this study was that treatment with varespladib, a small-molecule inhibitor of sPLA(2) would reduce postprocedural release of cardiac biomarkers after elective percutaneous coronary intervention.METHODS AND RESULTS: Between October 2007 and June 2009, 144 stable patients were randomized in a phase II trial to receive varespladib 500 mg PO BID or placebo 3 to 5 days before and for 5 days after elective percutaneous coronary intervention. ", "We evaluated whether endothelial function is attenuated after PCI and if inhibition of secretory phospholipase A2 (sPLA2) activity augments endothelial function and coronary flow reserve (CFR) in these patients.METHODS: In the sPLA2 Inhibition to Decrease Enzyme Release After Percutaneous Coronary Intervention (SPIDER-PCI) study, patients undergoing elective PCI were randomized to receive Varespladib (Anthera Pharmaceuticals Inc, San Mateo, CA), an inhibitor of sPLA2, or placebo 3-5 days prior to PCI and for 5 days after PCI. ", "The present study evaluated the effects of sPLA2-IIA inhibition with varespladib acid in a novel mouse model, human apolipoprotein B (apoB)/human cholesteryl ester transfer protein (CETP)/human sPLA2-IIA triple transgenic mice (TTT) fed a Western-type diet.APPROACH AND RESULTS: sPLA2-IIA expression increased atherosclerotic lesion formation in TTT compared with human apoB/human CETP double transgenic mice (P<0.01). Varespladib acid effectively inhibited plasma sPLA2-IIA activity. Surprisingly, however, administration of varespladib acid to TTT had no impact on atherosclerosis, which could be attributed to a proatherogenic plasma lipoprotein profile that appears in response to sPLA2-IIA inhibition because of increased plasma CETP activity. ", "Acute inhibition of sPLA2 activity with Varespladib does not affect endothelial or microvascular function after PCI.", "Varespladib acid effectively inhibited plasma sPLA2-IIA activity. Surprisingly, however, administration of varespladib acid to TTT had no impact on atherosclerosis, which could be attributed to a proatherogenic plasma lipoprotein profile that appears in response to sPLA2-IIA inhibition because of increased plasma CETP activity.", "We aimed at investigating the effect of co-administration of surfactant and varespladib on sPLA2 activity. Alveolar macrophages were cultured and stimulated with lipopolysaccharide and then treated with either varespladib, surfactant, varespladib followed by surfactant or nothing." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/23590147", "http://www.ncbi.nlm.nih.gov/pubmed/19697278", "http://www.ncbi.nlm.nih.gov/pubmed/24115030", "http://www.ncbi.nlm.nih.gov/pubmed/24247616", "http://www.ncbi.nlm.nih.gov/pubmed/23349189", "http://www.ncbi.nlm.nih.gov/pubmed/21602519", "http://www.ncbi.nlm.nih.gov/pubmed/21098449", "http://www.ncbi.nlm.nih.gov/pubmed/25533115", "http://www.ncbi.nlm.nih.gov/pubmed/24864079", "http://www.ncbi.nlm.nih.gov/pubmed/24419257", "http://www.ncbi.nlm.nih.gov/pubmed/22281412" ]

[]

[ "http://www.biosemantics.org/jochem#4240439", "http://www.biosemantics.org/jochem#4240440", "http://www.biosemantics.org/jochem#http://www.biosemantics.org/jochem#:4240439", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004798" ]

[ "Empagliflozin (Jardiance) is a SGLT2 inhibitor." ]

[ "SGLT2" ]

[ "Empagliflozin (Jardiance): a novel SGLT2 inhibitor for the treatment of type-2 diabetes.", "AIMS: Empagliflozin is a selective sodium glucose cotransporter 2 (SGLT2) inhibitor that inhibits renal glucose reabsorption and is being investigated for the treatment of type 2 diabetes mellitus (T2DM). ", "Effect of food on the pharmacokinetics of empagliflozin, a sodium glucose cotransporter 2 (SGLT2) inhibitor, and assessment of dose proportionality in healthy volunteers.", "Safety, tolerability, pharmacokinetics and pharmacodynamics of single doses of empagliflozin, a sodium glucose cotransporter 2 (SGLT2) inhibitor, in healthy Japanese subjects.", "Efficacy and safety of empagliflozin, a sodium glucose cotransporter 2 (SGLT2) inhibitor, as add-on to metformin in type 2 diabetes with mild hyperglycaemia.", "Pharmacokinetics, pharmacodynamics and safety of empagliflozin, a sodium glucose cotransporter 2 (SGLT2) inhibitor, in subjects with renal impairment.", "Pharmacokinetics of empagliflozin, a sodium glucose cotransporter-2 (SGLT2) inhibitor, and metformin following co-administration in healthy volunteers.", "Exposure-response modelling for empagliflozin, a sodium glucose cotransporter 2 (SGLT2) inhibitor, in patients with type 2 diabetes.", "Rationale, design and baseline characteristics of a 4-year (208-week) phase III trial of empagliflozin, an SGLT2 inhibitor, versus glimepiride as add-on to metformin in patients with type 2 diabetes mellitus with insufficient glycemic control.", "By inhibiting reabsorption of glucose from the proximal tubules in the kidney via inhibition of SGLT2, empagliflozin provides a novel insulin-independent mechanism of lowering blood glucose.", "Sodium glucose cotransporter 2 (SGLT2) inhibitors are a new class of treatment for T2DM that reduce hyperglycemia by reducing renal glucose reabsorption and thereby increasing urinary glucose excretion.This paper reviews the pharmacokinetic and pharmacodynamic properties of the SGLT2 inhibitor empagliflozin , the results of clinical trials investigating the efficacy of empagliflozin given as monotherapy or as add-on therapy on glycemic control, body weight, and blood pressure in patients with T2DM, and the safety and tolerability profile of empagliflozin.Empagliflozin offers good glycemic efficacy, weight loss, blood pressure reduction, and a low risk of hypoglycemia.", "Oral empagliflozin (Jardiance()), a sodium glucose cotransporter-2 (SGLT2) inhibitor, is a convenient once-daily treatment for adult patients with type 2 diabetes mellitus.", " This randomized, open-label, crossover study investigated potential drug-drug interactions between the sodium glucose cotransporter-2 (SGLT-2) inhibitor empagliflozin and the dipeptidyl peptidase-4 (DPP-4) inhibitor sitagliptin. Empagliflozin is a potent and selective SGLT-2 inhibitor that lowers blood glucose levels by inhibiting renal glucose reabsorption, leading to an increase in urinary glucose excretion.", "Empagliflozin is a potent, oral, selective inhibitor of sodium glucose cotransporter 2 in development for the treatment of type 2 diabetes mellitus. The goal of these studies was to investigate potential drug-drug interactions between empagliflozin and gemfibrozil (an organic anion-transporting polypeptide 1B1 [OATP1B1]/1B3 and organic anion transporter 3 [OAT3] inhibitor), rifampicin (an OATP1B1/1B3 inhibitor), or probenecid (an OAT3 and uridine diphosphate glucuronosyltransferase inhibitor).", "Empagliflozin, a novel selective sodium glucose cotransporter-2 (SGLT-2) inhibitor: characterisation and comparison with other SGLT-2 inhibitors.", " Empagliflozin is a potent and competitive SGLT-2 inhibitor with an excellent selectivity profile and the highest selectivity window of the tested SGLT-2 inhibitors over hSGLT-1. Empagliflozin represents an innovative therapeutic approach to treat diabetes.", "Empagliflozin, a novel selective sodium glucose cotransporter-2 (SGLT-2) inhibitor: characterisation and comparison with other SGLT-2 inhibitors.", "Empagliflozin is a selective sodium glucose cotransporter 2 (SGLT2) inhibitor that inhibits renal glucose reabsorption and is being investigated for the treatment of type 2 diabetes mellitus (T2DM).", "Empagliflozin is a potent and competitive SGLT-2 inhibitor with an excellent selectivity profile and the highest selectivity window of the tested SGLT-2 inhibitors over hSGLT-1.", "Pharmacokinetics, safety and tolerability of empagliflozin, a sodium glucose cotransporter 2 inhibitor, in patients with hepatic impairment.", "Pharmacokinetics, pharmacodynamics and safety of empagliflozin, a sodium glucose cotransporter 2 (SGLT2) inhibitor, in subjects with renal impairment.", "Compared with other SGLT-2 inhibitors, empagliflozin has a high degree of selectivity over SGLT-1, 4, 5 and 6.", "Safety, tolerability, pharmacokinetics and pharmacodynamics of single doses of empagliflozin, a sodium glucose cotransporter 2 (SGLT2) inhibitor, in healthy Japanese subjects.", "The SGLT2 inhibitor empagliflozin ameliorates early features of diabetic nephropathy in BTBR ob/ob type 2 diabetic mice with and without hypertension.", "Empagliflozin is an orally available, potent and highly selective inhibitor of the sodium glucose cotransporter 2 (SGLT2).", "This randomized, open-label, crossover study investigated potential drug-drug interactions between the sodium glucose cotransporter-2 (SGLT-2) inhibitor empagliflozin and the dipeptidyl peptidase-4 (DPP-4) inhibitor sitagliptin.", "Empagliflozin is a potent and selective SGLT-2 inhibitor that lowers blood glucose levels by inhibiting renal glucose reabsorption, leading to an increase in urinary glucose excretion." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/23398530", "http://www.ncbi.nlm.nih.gov/pubmed/25488697", "http://www.ncbi.nlm.nih.gov/pubmed/23054692", "http://www.ncbi.nlm.nih.gov/pubmed/24622320", "http://www.ncbi.nlm.nih.gov/pubmed/25369239", "http://www.ncbi.nlm.nih.gov/pubmed/25419452", "http://www.ncbi.nlm.nih.gov/pubmed/24226524", "http://www.ncbi.nlm.nih.gov/pubmed/24007456", "http://www.ncbi.nlm.nih.gov/pubmed/24993361", "http://www.ncbi.nlm.nih.gov/pubmed/24152604", "http://www.ncbi.nlm.nih.gov/pubmed/25260362", "http://www.ncbi.nlm.nih.gov/pubmed/22268612", "http://www.ncbi.nlm.nih.gov/pubmed/25598831", "http://www.ncbi.nlm.nih.gov/pubmed/24491572", "http://www.ncbi.nlm.nih.gov/pubmed/26045645", "http://www.ncbi.nlm.nih.gov/pubmed/25712444", "http://www.ncbi.nlm.nih.gov/pubmed/25402275", "http://www.ncbi.nlm.nih.gov/pubmed/23859534", "http://www.ncbi.nlm.nih.gov/pubmed/25274537", "http://www.ncbi.nlm.nih.gov/pubmed/24944269", "http://www.ncbi.nlm.nih.gov/pubmed/23390498", "http://www.ncbi.nlm.nih.gov/pubmed/23940010", "http://www.ncbi.nlm.nih.gov/pubmed/24964723", "http://www.ncbi.nlm.nih.gov/pubmed/25301180", "http://www.ncbi.nlm.nih.gov/pubmed/23253948", "http://www.ncbi.nlm.nih.gov/pubmed/24622369", "http://www.ncbi.nlm.nih.gov/pubmed/23859488", "http://www.ncbi.nlm.nih.gov/pubmed/21985634", "http://www.ncbi.nlm.nih.gov/pubmed/23906374", "http://www.ncbi.nlm.nih.gov/pubmed/23149871", "http://www.ncbi.nlm.nih.gov/pubmed/24463454", "http://www.ncbi.nlm.nih.gov/pubmed/25775379", "http://www.ncbi.nlm.nih.gov/pubmed/23497760" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D003924", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D051273", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D051297", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D003920" ]

[ "Muenke syndrome is an autosomal dominant disorder characterized by coronal suture craniosynostosis, hearing loss, developmental delay, carpal and tarsal fusions, and the presence of the Pro250Arg mutation in the FGFR3 gene. Muenke syndrome is characterized by coronal craniosynostosis (bilateral more often than unilateral), hearing loss, developmental delay, and carpal and/or tarsal bone coalition. Tarsal coalition is a distinct feature of Muenke syndrome and has been reported since the initial description of the disorder in the 1990s. ", "Muenke syndrome is characterized by considerable phenotypic variability: features may include coronal synostosis (more often bilateral than unilateral); synostosis of other sutures, all sutures (pansynostosis), or no sutures; or macrocephaly. Bilateral coronal synostosis typically results in brachycephaly (broad skull), although turribrachycephaly (a \"tower-shaped\" skull) or a cloverleaf skull can be observed. Unilateral coronal synostosis results in anterior plagiocephaly (asymmetry of the skull and face). Other craniofacial findings typically include: ocular hypertelorism, ptosis or proptosis (usually mild), midface hypoplasia, temporal bossing, and a highly arched palate. Strabismus is common. Extracranial findings can include: hearing loss (in 33%-100% of affected individuals); developmental delay (~33%); intellectual disability; carpal bone and/or tarsal bone fusions; brachydactyly, broad toes, broad thumbs, and/or clinodactyly; and radiographic findings of thimble-like (short and broad) middle phalanges and/or cone-shaped epiphyses. Phenotypic variability is considerable even within the same family." ]

[]

[ "Muenke syndrome is characterized by coronal craniosynostosis (bilateral more often than unilateral), hearing loss, developmental delay, and carpal and/or tarsal bone coalition. Tarsal coalition is a distinct feature of Muenke syndrome and has been reported since the initial description of the disorder in the 1990s. ", "Muenke syndrome caused by the FGFR3 Pro250Arg mutation is associated with craniosynostosis, hearing loss, and various bony anomalies.", "Muenke syndrome caused by the FGFR3(P250R) mutation is an autosomal dominant disorder mostly identified with coronal suture synostosis, but it also presents with other craniofacial phenotypes that include mild to moderate midface hypoplasia. ", "Sensorineural hearing loss at lower frequencies was found only in patients with Muenke syndrome. ", " Sensorineural hearing loss can occur in all 4 syndromes studied but is the primary cause of hearing loss in children and young adults with Muenke syndrome.", "The facial features of children with FGFR3Pro250Arg mutation (Muenke syndrome) differ from those with the other eponymous craniosynostotic disorders. We documented midfacial growth and position of the forehead after fronto-orbital advancement (FOA) in patients with the FGFR3 mutation. ", "The Muenke syndrome (MS) is characterized by unicoronal or bicoronal craniosynostosis, midfacial hypoplasia, ocular hypertelorism, and a variety of minor abnormalities associated with a mutation in the fibroblast growth factor receptor 3 (FGFR3) gene. ", "Muenke syndrome is characterized by considerable phenotypic variability: features may include coronal synostosis (more often bilateral than unilateral); synostosis of other sutures, all sutures (pansynostosis), or no sutures; or macrocephaly. Bilateral coronal synostosis typically results in brachycephaly (broad skull), although turribrachycephaly (a \"tower-shaped\" skull) or a cloverleaf skull can be observed. Unilateral coronal synostosis results in anterior plagiocephaly (asymmetry of the skull and face). Other craniofacial findings typically include: ocular hypertelorism, ptosis or proptosis (usually mild), midface hypoplasia, temporal bossing, and a highly arched palate. Strabismus is common. Extracranial findings can include: hearing loss (in 33%-100% of affected individuals); developmental delay (~33%); intellectual disability; carpal bone and/or tarsal bone fusions; brachydactyly, broad toes, broad thumbs, and/or clinodactyly; and radiographic findings of thimble-like (short and broad) middle phalanges and/or cone-shaped epiphyses. Phenotypic variability is considerable even within the same family. ", "Muenke syndrome is an autosomal dominant disorder characterized by coronal suture craniosynostosis, hearing loss, developmental delay, carpal and tarsal fusions, and the presence of the Pro250Arg mutation in the FGFR3 gene. ", "A majority of the patients (95%) demonstrated a mild-to-moderate, low frequency sensorineural hearing loss.", "Increased digital markings were more severe posteriorly in Muenke patients than in non-Muenke patients. The Muenke patients with unilateral coronal synostosis showed a somewhat more severe asymmetry in the anterior part of the skull than the non-Muenke patients.", "Muenke syndrome is a genetically determined craniosynostosis that involves one or both coronal sutures. In some patients it is associated with skeletal abnormalities such as thimble-like middle phalanges, coned epiphysis, and/or neurological impairment, namely sensorineural hearing loss or mental retardation.", "Muenke syndrome is an autosomal dominant disorder characterized by coronal suture craniosynostosis, hearing loss, developmental delay, carpal and tarsal fusions, and the presence of the Pro250Arg mutation in the FGFR3 gene.", "Muenke syndrome is characterized by various craniofacial deformities and is caused by an autosomal-dominant activating mutation in fibroblast growth factor receptor 3 (FGFR3(P250R) ).", "The Muenke syndrome (MS) is characterized by unicoronal or bicoronal craniosynostosis, midfacial hypoplasia, ocular hypertelorism, and a variety of minor abnormalities associated with a mutation in the fibroblast growth factor receptor 3 (FGFR3) gene.", "Muenke syndrome and FGFR2-related isolated coronal synostosis are characterized only by uni- or bicoronal craniosynostosis; the remainder are characterized by bicoronal craniosynostosis or cloverleaf skull, distinctive facial features, and variable hand and foot findings.", "Muenke syndrome is an autosomal-dominant craniosynostosis syndrome characterized by unilateral or bilateral coronal craniosynostosis, hearing loss, intellectual disability, and relatively subtle limb findings such as carpal bone fusion and tarsal bone fusion.", "Muenke syndrome is an autosomal dominant disorder characterized by coronal suture craniosynostosis, hearing loss, developmental delay, carpal and tarsal fusions, and the presence of the Pro250Arg mutation in the FGFR3 gene", "Muenke syndrome caused by the FGFR3 Pro250Arg mutation is associated with craniosynostosis, hearing loss, and various bony anomalies", "Muenke syndrome is characterized by coronal suture synostosis, midface hypoplasia, subtle limb anomalies, and hearing loss", "Muenke syndrome is an autosomal-dominant craniosynostosis syndrome characterized by unilateral or bilateral coronal craniosynostosis, hearing loss, intellectual disability, and relatively subtle limb findings such as carpal bone fusion and tarsal bone fusion", "Muenke syndrome is characterized by coronal craniosynostosis (bilateral more often than unilateral), hearing loss, developmental delay, and carpal and/or tarsal bone coalition", "Muenke syndrome is characterized by various craniofacial deformities and is caused by an autosomal-dominant activating mutation in fibroblast growth factor receptor 3 (FGFR3(P250R) )", "Muenke syndrome is an autosomal dominant disorder characterized by coronal suture craniosynostosis, hearing loss, developmental delay, carpal and tarsal fusions, and the presence of the Pro250Arg mutation in the FGFR3 gene" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/20301588", "http://www.ncbi.nlm.nih.gov/pubmed/17414289", "http://www.ncbi.nlm.nih.gov/pubmed/21844411", "http://www.ncbi.nlm.nih.gov/pubmed/22622662", "http://www.ncbi.nlm.nih.gov/pubmed/22446440", "http://www.ncbi.nlm.nih.gov/pubmed/14963686", "http://www.ncbi.nlm.nih.gov/pubmed/20592905", "http://www.ncbi.nlm.nih.gov/pubmed/18000976", "http://www.ncbi.nlm.nih.gov/pubmed/21403567", "http://www.ncbi.nlm.nih.gov/pubmed/20301628", "http://www.ncbi.nlm.nih.gov/pubmed/23378035", "http://www.ncbi.nlm.nih.gov/pubmed/22016144", "http://www.ncbi.nlm.nih.gov/pubmed/23044018" ]

[ { "p": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseasome/diseaseSubtypeOf", "s": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseases/3212", "o": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseases/779" }, { "p": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseasome/name", "s": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseases/779", "o": "Muenke_syndrome" }, { "p": "http://www.w3.org/2004/02/skos/core#exactMatch", "s": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseases/779", "o": "http://www.dbpedia.org/resource/Muenke_syndrome" }, { "p": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseasome/name", "s": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseases/3212", "o": "Muenke syndrome, 602849" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A17680562", "o": "C84904" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C1864436", "o": "http://linkedlifedata.com/resource/umls/label/A11927462" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C1864436", "o": "http://linkedlifedata.com/resource/umls/label/A17680562" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A11927462", "o": "MUENKE SYNDROME" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C1864436", "o": "http://linkedlifedata.com/resource/umls/label/A18467923" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A18449528", "o": "Muenke Syndrome" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A18467923", "o": "Syndrome of coronal craniosynostosis" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A11999362", "o": "MUENKE NONSYNDROMIC CORONAL CRANIOSYNOSTOSIS" }, { "p": "http://linkedlifedata.com/resource/umls/prefMetaMap", "s": "http://linkedlifedata.com/resource/umls/id/C1864436", "o": "http://linkedlifedata.com/resource/umls/label/A11999362" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C1864436", "o": "http://linkedlifedata.com/resource/umls/label/A18449529" }, { "p": "http://www.w3.org/2008/05/skos-xl#prefLabel", "s": "http://linkedlifedata.com/resource/umls/id/C1864436", "o": "http://linkedlifedata.com/resource/umls/label/A18449528" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A18449529", "o": "Muenke nonsyndromic coronal craniosynostosis" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A18449528", "o": "C537369" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A18449529", "o": "C537369" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A18467923", "o": "C537369" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A11927462", "o": "602849" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A11999362", "o": "602849" }, { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A18449528", "o": "MeSH" }, { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A18449529", "o": "MeSH" }, { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A18467923", "o": "MeSH" }, { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A11927462", "o": "OMIM" }, { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A11999362", "o": "OMIM" }, { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A17680562", "o": "NCI Thesaurus" }, { "p": "http://www.w3.org/2004/02/skos/core#broader", "s": "http://linkedlifedata.com/resource/umls/id/C1864436", "o": "http://linkedlifedata.com/resource/umls/id/C0010278" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A11993001", "o": "CRS" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A18466196", "o": "Craniostenoses" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A12007160", "o": "CRANIOSYNOSTOSIS, TYPE 1" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A17867080", "o": "Craniosynostosis" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A18447707", "o": "Craniosynostosis Plagiocephalies" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A0476812", "o": "craniosynostosis" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A18469337", "o": "Synostotic Plagiocephaly" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A8356736", "o": "Premature closure of cranial sutures" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A11935450", "o": "CRS1" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A18457001", "o": "Craniostenosis" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A18447706", "o": "Plagiocephaly, Craniosynostosis" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A18463141", "o": "Plagiocephaly, Synostotic" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A18460116", "o": "Plagiocephalies, Synostotic" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A0398432", "o": "CRANIOSYNOSTOSIS" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A17990682", "o": "Craniosynostoses" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A18469338", "o": "Craniosynostosis Plagiocephaly" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A18450823", "o": "Synostotic Plagiocephalies" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A12007161", "o": "CRANIOSTENOSIS" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A18014478", "o": "Craniosynostoses [Disease/Finding]" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A18457000", "o": "Plagiocephalies, Craniosynostosis" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A1305187", "o": "synostosis (cranial)" }, { "p": "http://www.w3.org/2004/02/skos/core#definition", "s": "http://linkedlifedata.com/resource/umls/id/C1864436", "o": "NCI: A rare autosomal dominant inherited disorder caused by mutations in the FGFR3 gene. It is characterized by premature fusion of cranial bones, resulting in head shape abnormalities, flattened cheekbones, and wide-set eyes." } ]

[ "http://www.disease-ontology.org/api/metadata/DOID:225", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012816", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013577" ]

[ "The predominant approach is to use versions of cognitive behavioural therapies, such as:\nMindfulness Based Therapy (MBT)\nMultimodal Anxiety and Social Skills Intervention (MASSI) program\nmodified version of the Coping Cat program, (cognitive-behavioral therapy; CBT)\nFamily cognitive-behavioral therapy has been found to be more effective than Individual cognitive-behavioral therapy \nConflict management for couples, even when conflict and family distress is low\n\nDrugtherapy: \nSertraline" ]

[ "Mindfulness Based Therapy (MBT)", "Multimodal Anxiety and Social Skills Intervention (MASSI) program", "modified version of the Coping Cat program", "(cognitive-behavioral therapy; CBT", "Family cognitive-behavioral therapy", "Individual cognitive-behavioral therapy", "Conflict management for couples", "even when conflict and family distress is low", "Sertraline" ]

[ "A parent report of comorbid diagnosis of attention-deficit/hyperactivity disorder, bipolar disorder, obsessive-compulsive disorder, depression, or anxiety was associated with a high rate of use, with 80% receiving ≥ 1 psychotropic medication", "Mindfulness-based therapy (MBT) has been found effective in reducing anxiety and depression symptoms, however research in autism is limited.", "Therefore, we examined the effects of a modified MBT protocol (MBT-AS) in high-functioning adults with ASD.", "the present study is the first controlled trial to demonstrate that adults with ASD can benefit from MBT-AS.", "This pilot, randomized controlled trial evaluated the feasibility and preliminary outcomes of the Multimodal Anxiety and Social Skills Intervention (MASSI) program in a sample of 30 adolescents with ASD and anxiety symptoms of moderate or greater severity.", "These findings suggest MASSI is a feasible treatment program and further evaluation is warranted.", "The purpose of this pilot study was to evaluate whether a modified version of the Coping Cat program could be effective in reducing anxiety in children with autism spectrum disorder (ASD).", "the Coping Cat program (cognitive-behavioral therapy; CBT)", "Results provide preliminary evidence that a modified version of the Coping Cat program may be a feasible and effective program for reducing clinically significant levels of anxiety in children with high-functioning ASD.", "The intent of this article is to explore the efficacy of both the literal and concrete externalization aspects within narrative therapy, and the implementation of interactive metaphors as a combined psychotherapeutic approach for decreasing anxiety with people who present with high-functioning autism.", "This paper reports a case series of children and adolescents with ASD and an anxiety disorder who were treated with a standard cognitive behaviour therapy (CBT) rationale adapted to take account of the neuropsychological features of ASD.", "children with moderate autistic symptomology (per SRS-P) were significantly more likely to improve from family CBT (FCBT) than individual CBT (ICBT; OR = 8.67)", "Though both treatments reduced anxiety, FCBT outperformed ICBT for children with moderate ASD symptoms, a benefit potentially linked to more at-home exposures and greater child involvement in FCBT.", "A structural model-building approach was used to test the extent to which family and peer variables directly or indirectly affected ASD via child anxiety/depression.", "The key findings were that anxiety/depression and ASD symptomatology were significantly related, and family conflict was more predictive of ASD symptomatology than positive family/peer influences. The results point to the utility of expanding interventions to include conflict management for couples, even when conflict and family distress is low.", "A family-based, cognitive behavioural treatment for anxiety in 47 children with comorbid anxiety disorders and High Functioning Autism Spectrum Disorder (HFA) was evaluated.", "Following treatment, 71.4% of the treated participants no longer fulfilled diagnostic criteria for an anxiety disorder. Comparisons between the two conditions indicated significant reductions in anxiety symptoms as measured by self-report, parent report and teacher report" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/18437549", "http://www.ncbi.nlm.nih.gov/pubmed/22964266", "http://www.ncbi.nlm.nih.gov/pubmed/22735897", "http://www.ncbi.nlm.nih.gov/pubmed/23118256", "http://www.ncbi.nlm.nih.gov/pubmed/22588377", "http://www.ncbi.nlm.nih.gov/pubmed/21571763", "http://www.ncbi.nlm.nih.gov/pubmed/17171539", "http://www.ncbi.nlm.nih.gov/pubmed/20694508", "http://www.ncbi.nlm.nih.gov/pubmed/22299802", "http://www.ncbi.nlm.nih.gov/pubmed/22934167" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D002659", "http://www.disease-ontology.org/api/metadata/DOID:2030", "http://www.disease-ontology.org/api/metadata/DOID:12849", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001007", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001008", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001321", "http://www.disease-ontology.org/api/metadata/DOID:0060041" ]

[ "Istradefylline and preladenant are adenosine A2A receptor antagonists that are used for Parkinson's disease treatment." ]

[ "istradefylline", "preladenant" ]

[ "Adenosine A2A antagonists, such as istradefylline, improve motor function in PD, but their effect on cognitive impairment has not been determined.", "Both istradefylline and preladenant have demonstrated moderate efficacy in reducing off time in PD patients with motor fluctuations. ", " The available data also suggest that caffeine can improve the motor deficits of PD and that adenosine A2A receptor antagonists such as istradefylline reduces OFF time and dyskinesia associated with standard 'dopamine replacement' treatments. ", "Istradefylline (KW-6002) is the first of several adenosine A2A receptor antagonists in development for PD to advance to phase III clinical trials. Initial studies indicate that in patients with motor fluctuations on levodopa, addition of istradefylline reduces 'off' time. ", "These include alpha2 adrenergic receptor antagonists (eg, fipamezole), adenosine A2A receptor antagonists (eg, istradefylline), AMPA receptor antagonists (eg, talampanel), neuronal synchronization modulators (eg, levetiracetam) and agents that interact with serotonergic systems such as 5-hydroxytryptamine (5-HT)1A agonists (eg, sarizotan) and 5-HT2A antagonists (eg, quetiapine). ", "BACKGROUND: We evaluated the efficacy and safety of istradefylline, a selective adenosine A2A receptor antagonist administered as adjunctive treatment to levodopa for 12 weeks in a double-blind manner in Parkinsons disease patients with motor complications in Japan.", "Istradefylline, a novel adenosine A2A receptor antagonist, for the treatment of Parkinsons disease.", "Istradefylline, a novel adenosine A2A receptor antagonist, for the treatment of Parkinson's disease.", "In this article, the author discusses the potential role of A2A adenosine receptor antagonists in the treatment of Parkinson's disease through the evaluation of istradefylline", "Suitability of the adenosine antagonist istradefylline for the treatment of Parkinson's disease: pharmacokinetic and clinical considerations." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/23748382", "http://www.ncbi.nlm.nih.gov/pubmed/20182024", "http://www.ncbi.nlm.nih.gov/pubmed/24687255", "http://www.ncbi.nlm.nih.gov/pubmed/15298067", "http://www.ncbi.nlm.nih.gov/pubmed/22585137", "http://www.ncbi.nlm.nih.gov/pubmed/25175961", "http://www.ncbi.nlm.nih.gov/pubmed/15974638", "http://www.ncbi.nlm.nih.gov/pubmed/23483627", "http://www.ncbi.nlm.nih.gov/pubmed/16004599", "http://www.ncbi.nlm.nih.gov/pubmed/23642267" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D058917", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D010300", "http://www.disease-ontology.org/api/metadata/DOID:14330" ]

[ "T1 mapping can quantitatively characterize myocardial tissue, in particular diffuse and interstitial fibrosis, edema in both overt and subclinical cardiophyopathies. However more research is required before a large-scale application for clinical decision-making can be recommended.", "The clinical indication of cardiac T1 mapping magnetic resonance is the detection of diffuse myocardial fibrosis in nonischemic cardiomyopathies" ]

[ "detection of myocardial fibrosis in nonischemic cardiomyopathies", "T1 mapping can quantitatively characterize myocardial tissue, i.e. fibrosis and edema." ]

[ "More diverse patterns of late enhancement including patchy, mid-wall, subepicardial, or diffuse enhancement are of interest in diagnosing nonischemic cardiomyopathies.", "Methods for quantification of T1 and extracellular volume fraction are emerging to tackle the issue of discriminating globally diffuse fibrosis from normal healthy tissue which is challenging using conventional late enhancement methods. ", "Recent T1 mapping techniques aim to overcome the limitations of late gadolinium enhancement to assess diffuse fibrosis.", "T1 mapping techniques performed both with and without contrast are enabling quantification of diffuse myocardial fibrosis and myocardial infiltration.", "Noncontrast T1 mapping has high diagnostic accuracy for detecting cardiac AL amyloidosis, correlates well with markers of systolic and diastolic dysfunction, and is potentially more sensitive for detecting early disease than LGE imaging.", "T1 mapping has been proposed as potentially valuable in the quantitative assessment of diffuse myocardial fibrosis, but no studies to date have systematically evaluated its role in the differentiation of healthy myocardium from diffuse disease in a clinical setting. ", "This study demonstrates that native and post-contrast T1 values provide indexes with high diagnostic accuracy for the discrimination of normal and diffusely diseased myocardium.", "T1 values lengthened with greater LVMI and correlated with the degree of biopsy-quantified fibrosis. This may provide a useful clinical assessment of diffuse myocardial fibrosis in the future.", "Cardiac magnetic resonance (CMR) T1 mapping has been used to characterize myocardial diffuse fibrosis. ", "In HCM and DCM, noncontrast T1 mapping detects underlying disease processes beyond those assessed by LGE in relatively low-risk individuals." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/23564562", "http://www.ncbi.nlm.nih.gov/pubmed/22720998", "http://www.ncbi.nlm.nih.gov/pubmed/12765114", "http://www.ncbi.nlm.nih.gov/pubmed/24518490", "http://www.ncbi.nlm.nih.gov/pubmed/24036385", "http://www.ncbi.nlm.nih.gov/pubmed/24566951", "http://www.ncbi.nlm.nih.gov/pubmed/25310419", "http://www.ncbi.nlm.nih.gov/pubmed/24011774", "http://www.ncbi.nlm.nih.gov/pubmed/17896383", "http://www.ncbi.nlm.nih.gov/pubmed/23549230", "http://www.ncbi.nlm.nih.gov/pubmed/22279111", "http://www.ncbi.nlm.nih.gov/pubmed/24425501", "http://www.ncbi.nlm.nih.gov/pubmed/24931636", "http://www.ncbi.nlm.nih.gov/pubmed/21974927", "http://www.ncbi.nlm.nih.gov/pubmed/23071146", "http://www.ncbi.nlm.nih.gov/pubmed/23349348", "http://www.ncbi.nlm.nih.gov/pubmed/23643513", "http://www.ncbi.nlm.nih.gov/pubmed/24903343", "http://www.ncbi.nlm.nih.gov/pubmed/17659622", "http://www.ncbi.nlm.nih.gov/pubmed/22967246", "http://www.ncbi.nlm.nih.gov/pubmed/19007595", "http://www.ncbi.nlm.nih.gov/pubmed/23403334", "http://www.ncbi.nlm.nih.gov/pubmed/24472162", "http://www.ncbi.nlm.nih.gov/pubmed/23272704", "http://www.ncbi.nlm.nih.gov/pubmed/24043965", "http://www.ncbi.nlm.nih.gov/pubmed/23408722", "http://www.ncbi.nlm.nih.gov/pubmed/24058912", "http://www.ncbi.nlm.nih.gov/pubmed/22161952", "http://www.ncbi.nlm.nih.gov/pubmed/22309452", "http://www.ncbi.nlm.nih.gov/pubmed/22710483", "http://www.ncbi.nlm.nih.gov/pubmed/25424139", "http://www.ncbi.nlm.nih.gov/pubmed/23845576", "http://www.ncbi.nlm.nih.gov/pubmed/24576837", "http://www.ncbi.nlm.nih.gov/pubmed/23280998", "http://www.ncbi.nlm.nih.gov/pubmed/23890156", "http://www.ncbi.nlm.nih.gov/pubmed/24124732", "http://www.ncbi.nlm.nih.gov/pubmed/23498672", "http://www.ncbi.nlm.nih.gov/pubmed/22903654", "http://www.ncbi.nlm.nih.gov/pubmed/23498674" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D008279", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D006321" ]

[ "Cytosolic proteins carrying the KFERQ motif (a specific lysosomal import consensus sequence) are directed to a selective form of lysosomal degradation, called chaperone-mediated autophagy (CMA), as chaperone protein Hsc73 and other chaperones are involved in this process." ]

[ "chaperone-mediated autophagy (CMA)" ]

[ "Chaperone-mediated autophagy (CMA) is a selective form of lysosomal degradation targeting proteins carrying the KFERQ motif.", "The significance of the receptor glycoprotein lamp2a in the chaperone-mediated autophagy of cytosolic proteins with KFERQ motif has been described in details as well as the chaperone protein Hsc73 and other chaperones involved in this process.", "We investigated chaperone-mediated autophagy, a lysosomal import pathway that depends on the 73-kDa heat shock cognate protein and allows the degradation of proteins containing a specific lysosomal import consensus sequence (KFERQ motif). ", "The significance of the receptor glycoprotein lamp2a in the chaperone-mediated autophagy of cytosolic proteins with KFERQ motif has been described in details as well as the chaperone protein Hsc73 and other chaperones involved in this process.", "We investigated chaperone-mediated autophagy, a lysosomal import pathway that depends on the 73-kDa heat shock cognate protein and allows the degradation of proteins containing a specific lysosomal import consensus sequence (KFERQ motif).", "Chaperone-mediated autophagy (CMA) is a selective form of lysosomal degradation targeting proteins carrying the KFERQ motif.", "Chaperone-mediated autophagy (CMA) is a selective mechanism for the degradation of soluble cytosolic proteins bearing the sequence KFERQ.", "The abundance of proteins containing that chaperone-mediated autophagy KFERQ signal motif increased 38% and individual KFERQ containing proteins [e.", "Furthermore, four annexins containing KFERQ-like sequences, annexins I, II, IV, and VI, are enriched in lysosomes with high chaperone-mediated autophagy activity as expected for substrate proteins.", "Using isolated lysosomes, only the annexins containing KFERQ-like sequences are degraded by chaperone mediated-autophagy.", "Macroautophagy is followed by chaperone-mediated autophagy (CMA), in which Hsc70 (Heat shock cognate 70) selectively binds proteins with exposed KFERQ motifs and pushes them inside lysosomes through the LAMP-2A (Lysosome-associated membrane protein type 2A) receptor.", "Macroautophagy is followed by chaperone-mediated autophagy (CMA), in which Hsc70 (Heat shock cognate 70) selectively binds proteins with exposed KFERQ motifs and pushes them inside lysosomes through the LAMP-2A (Lysosome-associated membrane protein type 2A) receptor.", "AIMS: Chaperone-mediated autophagy (CMA) is a selective mechanism for the degradation of soluble cytosolic proteins bearing the sequence KFERQ.", "We investigated chaperone-mediated autophagy, a lysosomal import pathway that depends on the 73-kDa heat shock cognate protein and allows the degradation of proteins containing a specific lysosomal import consensus sequence (KFERQ motif).", "The significance of the receptor glycoprotein lamp2a in the chaperone-mediated autophagy of cytosolic proteins with KFERQ motif has been described in details as well as the chaperone protein Hsc73 and other chaperones involved in this process", "Chaperone-mediated autophagy (CMA) is a selective mechanism for the degradation of soluble cytosolic proteins bearing the sequence KFERQ", "In cell culture, growth factors suppress the lysosomal pathway of chaperone-mediated autophagy leading to the accumulation of specific cytoplasmic proteins containing KFERQ motifs", "We investigated chaperone-mediated autophagy, a lysosomal import pathway that depends on the 73-kDa heat shock cognate protein and allows the degradation of proteins containing a specific lysosomal import consensus sequence (KFERQ motif)", "The abundance of proteins containing that chaperone-mediated autophagy KFERQ signal motif increased 38% and individual KFERQ containing proteins [e.g., M2 pyruvate kinase, glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and pax2] were more abundant", "These results provide striking evidence for the importance of KFERQ motifs in substrates of chaperone-mediated autophagy.", "Macroautophagy is followed by chaperone-mediated autophagy (CMA), in which Hsc70 (Heat shock cognate 70) selectively binds proteins with exposed KFERQ motifs and pushes them inside lysosomes through the LAMP-2A (Lysosome-associated membrane protein type 2A) receptor" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/15149326", "http://www.ncbi.nlm.nih.gov/pubmed/24477641", "http://www.ncbi.nlm.nih.gov/pubmed/23452232", "http://www.ncbi.nlm.nih.gov/pubmed/11262416", "http://www.ncbi.nlm.nih.gov/pubmed/10938088", "http://www.ncbi.nlm.nih.gov/pubmed/12105396", "http://www.ncbi.nlm.nih.gov/pubmed/19433452", "http://www.ncbi.nlm.nih.gov/pubmed/23880665", "http://www.ncbi.nlm.nih.gov/pubmed/23070014", "http://www.ncbi.nlm.nih.gov/pubmed/24323530", "http://www.ncbi.nlm.nih.gov/pubmed/16782460", "http://www.ncbi.nlm.nih.gov/pubmed/23404999", "http://www.ncbi.nlm.nih.gov/pubmed/16209346" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001343", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0006914", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D054730" ]

[ "Tuberous sclerosis or tuberous sclerosis complex (TSC) is a rare multi-system genetic disease that causes benign tumors to grow in the brain and on other vital organs such as the kidneys, heart, eyes, lungs, and skin. A combination of symptoms may include seizures, intellectual disability, developmental delay, behavioral problems, skin abnormalities, lung and kidney disease. TSC is caused by a mutation of either of two genes, TSC1 and TSC2, which code for the proteins hamartin and tuberin respectively. These proteins act as tumor growth suppressors, agents that regulate cell proliferation and differentiation." ]

[ "Brain lesions", "Kidney lesions", "Lung lesions", "renal angiomyolipoma", "subependymal giant cell astrocytoma (SEGA)", "seizures", "mental detardation", "autism", "hepatic lesions", "Pulmonary lymphangioleiomyomatosis" ]

[ "Most cases of tuberous sclerosis complex are complicated with bilateral multiple renal angiomyolipoma.", "Periodic imaging surveillance for development of subependymal giant cell astrocytoma (SEGA), preferably by magnetic resonance imaging (MRI) every 1-3 years, is now standard of care", " Although large tubers are less common than small to medium-sized ones, they are much more likely to be accompanied by severe clinical symptoms (seizures, mental retardation and autistic behaviour), even when the smaller tubers are quite numerous", "Hepatic angiomyolipomas (AML), cysts, and other benign lesions were identified in 30% of the cohort, and some lesions grew significantly over time. ", "Pulmonary lymphangioleiomyomatosis and bilateral renal angiomyolipomas are some presentations of tuberous sclerosis and the coexistence of both conditions may cause devastating morbidity and mortality.", "uberous sclerosis, a genetic, rare, variably expressed disease. Clinical symptoms were chest pain, and progressive dyspnea. Computed tomography scan of the chest showed bilateral, diffuse, small thin-walled cysts scattered throughout the lungs characteristic for pulmonary lymphangioleiomyomatosis." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/15220823", "http://www.ncbi.nlm.nih.gov/pubmed/8375445", "http://www.ncbi.nlm.nih.gov/pubmed/9657027", "http://www.ncbi.nlm.nih.gov/pubmed/8585387", "http://www.ncbi.nlm.nih.gov/pubmed/9973956", "http://www.ncbi.nlm.nih.gov/pubmed/21372179", "http://www.ncbi.nlm.nih.gov/pubmed/21919012", "http://www.ncbi.nlm.nih.gov/pubmed/10215407", "http://www.ncbi.nlm.nih.gov/pubmed/6775242", "http://www.ncbi.nlm.nih.gov/pubmed/8181495", "http://www.ncbi.nlm.nih.gov/pubmed/16459994", "http://www.ncbi.nlm.nih.gov/pubmed/22438024", "http://www.ncbi.nlm.nih.gov/pubmed/23776883", "http://www.ncbi.nlm.nih.gov/pubmed/16529961", "http://www.ncbi.nlm.nih.gov/pubmed/20184711", "http://www.ncbi.nlm.nih.gov/pubmed/7587886", "http://www.ncbi.nlm.nih.gov/pubmed/23274119", "http://www.ncbi.nlm.nih.gov/pubmed/24169285", "http://www.ncbi.nlm.nih.gov/pubmed/18325099", "http://www.ncbi.nlm.nih.gov/pubmed/22251200", "http://www.ncbi.nlm.nih.gov/pubmed/16329102", "http://www.ncbi.nlm.nih.gov/pubmed/15874888", "http://www.ncbi.nlm.nih.gov/pubmed/2208245", "http://www.ncbi.nlm.nih.gov/pubmed/23852707" ]

[ { "p": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseasome/associatedGene", "s": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseases/4099", "o": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/genes/TSC2" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/genes/TSC2", "o": "TSC2" }, { "p": "http://www.w3.org/2004/02/skos/core#exactMatch", "s": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/genes/TSC2", "o": "http://www.dbpedia.org/resource/TSC2" }, { "p": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseasome/name", "s": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseases/4099", "o": "Tuberous sclerosis-2, 191100" }, { "p": "http://purl.uniprot.org/core/mnemonic", "s": "http://purl.uniprot.org/uniprot/Q9UUG9", "o": "TSC2_SCHPO" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_513955554739008", "o": "Tuberous sclerosis 2 protein homolog" }, { "p": "http://purl.uniprot.org/core/recommendedName", "s": "http://purl.uniprot.org/uniprot/Q9UUG9", "o": "http://linkedlifedata.com/resource/#_513955554739008" }, { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A12023964", "o": "OMIM" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A12023964", "o": "Associated with tuberous sclerosis ({191100})" }, { "p": "http://www.w3.org/2008/05/skos-xl#prefLabel", "s": "http://linkedlifedata.com/resource/umls/id/C1837693", "o": "http://linkedlifedata.com/resource/umls/label/A12023964" }, { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A11925970", "o": "OMIM" }, { "p": "http://linkedlifedata.com/resource/umls/altMetaMap", "s": "http://linkedlifedata.com/resource/umls/id/C1854459", "o": "http://linkedlifedata.com/resource/umls/label/A11925970" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A11997913", "o": "TUBEROUS SCLEROSIS 1, LEU250TER" }, { "p": "http://linkedlifedata.com/resource/umls/prefMetaMap", "s": "http://linkedlifedata.com/resource/umls/id/C1854459", "o": "http://linkedlifedata.com/resource/umls/label/A11997913" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A11925970", "o": "TSC1, LEU250TER" }, { "p": "http://www.w3.org/2008/05/skos-xl#prefLabel", "s": "http://linkedlifedata.com/resource/umls/id/C1854459", "o": "http://linkedlifedata.com/resource/umls/label/A11997913" }, { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A11997913", "o": "OMIM" }, { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A17460634", "o": "OMIM" }, { "p": "http://www.w3.org/2008/05/skos-xl#prefLabel", "s": "http://linkedlifedata.com/resource/umls/id/C2751561", "o": "http://linkedlifedata.com/resource/umls/label/A17464209" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C2751561", "o": "http://linkedlifedata.com/resource/umls/label/A17460634" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A17464209", "o": "TUBEROUS SCLEROSIS 1, MET224ARG" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A17460634", "o": "TSC1, MET224ARG" }, { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A17464209", "o": "OMIM" }, { "p": "http://linkedlifedata.com/resource/relationontology/binding", "s": "http://purl.uniprot.org/uniprot/Q09778", "o": "http://purl.uniprot.org/uniprot/Q9UUG9" }, { "p": "http://purl.uniprot.org/core/recommendedName", "s": "http://purl.uniprot.org/uniprot/Q09778", "o": "http://linkedlifedata.com/resource/#_513039373738006" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_513039373738006", "o": "Tuberous sclerosis 1 protein homolog" }, { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A17462986", "o": "OMIM" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A17462986", "o": "TUBEROUS SCLEROSIS 1, LEU180PRO" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A17462987", "o": "TSC1, LEU180PRO" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C2751562", "o": "http://linkedlifedata.com/resource/umls/label/A17462987" }, { "p": "http://www.w3.org/2008/05/skos-xl#prefLabel", "s": "http://linkedlifedata.com/resource/umls/id/C2751562", "o": "http://linkedlifedata.com/resource/umls/label/A17462986" }, { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A17462987", "o": "OMIM" }, { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A11954787", "o": "OMIM" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A11969101", "o": "TUBEROUS SCLEROSIS 1, LYS585ARG" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A11954787", "o": "TSC1, LYS585ARG" }, { "p": "http://linkedlifedata.com/resource/umls/prefMetaMap", "s": "http://linkedlifedata.com/resource/umls/id/C1854460", "o": "http://linkedlifedata.com/resource/umls/label/A11969101" }, { "p": "http://www.w3.org/2008/05/skos-xl#prefLabel", "s": "http://linkedlifedata.com/resource/umls/id/C1854460", "o": "http://linkedlifedata.com/resource/umls/label/A11969101" }, { "p": "http://linkedlifedata.com/resource/umls/altMetaMap", "s": "http://linkedlifedata.com/resource/umls/id/C1854460", "o": "http://linkedlifedata.com/resource/umls/label/A11954787" }, { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A11969101", "o": "OMIM" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A12023964", "o": "MTHU001988" }, { "p": "http://purl.uniprot.org/core/citation", "s": "http://purl.uniprot.org/uniprot/Q09778", "o": "http://purl.uniprot.org/citations/11859360" }, { "p": "http://purl.uniprot.org/core/name", "s": "http://purl.uniprot.org/pubmed/11859360", "o": "Nature" }, { "p": "http://www.w3.org/2004/02/skos/core#exactMatch", "s": "http://purl.uniprot.org/pubmed/11859360", "o": "http://purl.uniprot.org/pubmed/11859360" }, { "p": "http://www.w3.org/2004/02/skos/core#exactMatch", "s": "http://purl.uniprot.org/pubmed/11859360", "o": "http://purl.uniprot.org/medline/21848401" } ]

[ "http://www.uniprot.org/uniprot/TSC2_RAT", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0033596", "http://www.uniprot.org/uniprot/TSC1_RAT", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012598", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D014402", "http://www.uniprot.org/uniprot/TSC1_SCHPO", "http://www.uniprot.org/uniprot/TSC1_HUMAN", "http://www.uniprot.org/uniprot/TSC2_SCHPO", "http://www.disease-ontology.org/api/metadata/DOID:13515", "http://www.biosemantics.org/jochem#4266396", "http://www.uniprot.org/uniprot/TSC2_HUMAN" ]

[ "Dabigatran increases aPTT in patients with atrial fibrillation, although aPTT does not respond linearily to dabigatran therapy." ]

[]

[ "He had been started on dabigatran 150 mg twice a day about 4 months ago as an outpatient by his cardiologist. His prothrombin time (PT) was 63 seconds with international normalized ratio (INR) of 8.8 and his activated partial thromboplastin time (aPTT) was 105.7 seconds. ", "The aPTT assay is relatively insensitive to dabigatran, and normal aPTT results may be observed even with therapeutic dabigatran concentrations.", "The APTT values became prolonged under dabigatran usage and exhibited a remarkable diversity. Although major bleeding did not occur unless APTT was prolonged excessively, minor bleeding arose irrespective of the APTT values even within the range of the APTT values not exceeding 80s.", "Dabigatran led to a dose-dependent prolongation of the clotting times in coagulometric tests and influenced the majority of the parameters measured. Statistically significant interference could be observed with the prothrombin time (PT), activated partial thromboplastin time (aPTT) and PT/aPTT-based assays (extrinsic/intrinsic factors, APC-resistance test) as well as lupus anticoagulant testing.", "Although aPTT does not provide a linear response to dabigatran therapy, the presence of a completely normal PTT may exclude therapeutic dabigatran anticoagulation.", "Commonly available global coagulation time assessments (e.g. prothrombin time and activated partial thromboplastin time) are highly influenced by rivaroxaban and dabigatran but these assays are relatively insensitive. ", "The relationship between dabigatran plasma concentrations and activated partial thromboplastin time in healthy volunteers and patients (n=762) was best described with a combination of a linear model and a maximum effect (Emax) model, consistent with previous reports. ", "We found a wide distribution of APTT in NVAF patients under dabigatran treatment. High APTT might help screen for bleeding risks among patients under dabigatran, but requires future investigation." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/23100377", "http://www.ncbi.nlm.nih.gov/pubmed/23784008", "http://www.ncbi.nlm.nih.gov/pubmed/22608344", "http://www.ncbi.nlm.nih.gov/pubmed/22539097", "http://www.ncbi.nlm.nih.gov/pubmed/23680005", "http://www.ncbi.nlm.nih.gov/pubmed/24151507", "http://www.ncbi.nlm.nih.gov/pubmed/22398858", "http://www.ncbi.nlm.nih.gov/pubmed/22293451" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001281", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D010314", "http://www.biosemantics.org/jochem#4242811" ]

[ "AFP-I\nAFP-II\nAFP-III\nAnti-freeze glycoprotein\nThermal hysteresis protein" ]

[ "anti-freeze protein-3", "AFP-III", "anti-freeze glycoprotein", "Thermal hysteresis protein", "AFP-I", "AFP-II" ]

[ "the anti-freeze glycoprotein of Antarctic and Arctic notothenoids, ", "pe III anti-freeze protein (AFP)", "AFP I or AFP III", "type III anti-freeze proteins ", "wild type III thermal hysteresis protein", "Thermal hysteresis proteins (THPs) have been found in vertebrates, invertebrates, plants, bacteria and fungi and are able to depress the freezing point of water (in the presence of ice crystals) in a non-colligative manner by binding to the surface of nascent ice crystals", "skin-type anti-freeze protein-3" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/19857362", "http://www.ncbi.nlm.nih.gov/pubmed/23479899", "http://www.ncbi.nlm.nih.gov/pubmed/17189482", "http://www.ncbi.nlm.nih.gov/pubmed/10405170", "http://www.ncbi.nlm.nih.gov/pubmed/15059666", "http://www.ncbi.nlm.nih.gov/pubmed/16297800", "http://www.ncbi.nlm.nih.gov/pubmed/12065219", "http://www.ncbi.nlm.nih.gov/pubmed/17553775", "http://www.ncbi.nlm.nih.gov/pubmed/11240367", "http://www.ncbi.nlm.nih.gov/pubmed/15146494", "http://www.ncbi.nlm.nih.gov/pubmed/22180206" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011506", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0009409", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0050826", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005615", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0033637" ]

[ "The promoter paused form of RNA polymerase II is phosphorylated on serine 5 residues of the C-terminal heptapeptide repeat domain (CTD) of the largest subunit." ]

[ "Serine 5" ]

[ "increase levels of serine-5 phosphorylated RNA polymerase II in the mutation target region, consistent with an effect on transcriptional elongation/pausing", "pol-II accumulated in the 5'-region of the gene, which indicated postinitiation pausing. pol-II binding, 5'-accumulation, C-terminal domain Ser-5 and Ser-2 phosphorylation", "The carboxy-terminal domain of the paused polymerase large subunit is hyperphosphorylated on serine 5, and phosphorylation of serine 2 is first detected here", "the promoter-paused form of Pol II (Pol IIo(ser5)", "Pause release depends on Cdk9-cyclin T1 (P-TEFb); Cdk7 is also required for Cdk9-activating phosphorylation and Cdk9-dependent downstream events--Pol II C-terminal domain Ser2 phosphorylation ", "For genes containing a 5' paused polymerase, passage of the paused RNA polymerase into an elongationally competent mode in vivo coincides with phosphorylation of the CTD", "Ser-5 phosphorylation of Pol II is concentrated near the promoter", "the promoter-paused Pol II shows Ser5 but not Ser2 phosphorylation" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/8015613", "http://www.ncbi.nlm.nih.gov/pubmed/17942706", "http://www.ncbi.nlm.nih.gov/pubmed/12612070", "http://www.ncbi.nlm.nih.gov/pubmed/21095588", "http://www.ncbi.nlm.nih.gov/pubmed/21385935", "http://www.ncbi.nlm.nih.gov/pubmed/23087403", "http://www.ncbi.nlm.nih.gov/pubmed/14560008" ]

[]

[ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0001055", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012319", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0071620", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0071619" ]

[ "Overexpression of sirtuins (NAD(+)-dependent protein deacetylases) has been reported to increase lifespan in budding yeast (Saccharomyces cerevisiae)." ]

[ "yes" ]

[ "In addition, Sir2 overexpression prevents Rif1 deletion from disrupting Sir2 at IGS1 and shortening lifespan. ", "Roles for sirtuin proteins at telomeres are thought to promote lifespan in yeast and mammals.", "Overexpression of sirtuins (NAD(+)-dependent protein deacetylases) has been reported to increase lifespan in budding yeast (Saccharomyces cerevisiae)", "When overexpressed, the NAD-dependent protein deacetylase Sir2 extends the lifespan of both budding yeast ", "When overexpressed in primary mouse embryo fibroblasts (MEFs), SIRT1 antagonizes PML-induced acetylation of p53 and rescues PML-mediated premature cellular senescence. " ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/12006491", "http://www.ncbi.nlm.nih.gov/pubmed/21938067", "http://www.ncbi.nlm.nih.gov/pubmed/15308206", "http://www.ncbi.nlm.nih.gov/pubmed/23082874" ]

[]

[ "http://www.uniprot.org/uniprot/SIR2_MOUSE", "http://www.uniprot.org/uniprot/SIR2_HUMAN", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004718", "http://www.uniprot.org/uniprot/SIR6_HUMAN", "http://www.uniprot.org/uniprot/SIR3_MOUSE", "http://www.uniprot.org/uniprot/SIR7_HUMAN", "http://www.uniprot.org/uniprot/SIR6_MOUSE", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D015003", "http://www.uniprot.org/uniprot/SIR2_PONAB", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D037761", "http://www.uniprot.org/uniprot/SIR2_DANRE", "http://www.uniprot.org/uniprot/SIR7_MOUSE", "http://www.uniprot.org/uniprot/SIR4_HUMAN", "http://www.uniprot.org/uniprot/SIR4_BOVIN", "http://www.uniprot.org/uniprot/SIR1_HUMAN", "http://www.uniprot.org/uniprot/SIR7_BOVIN", "http://www.uniprot.org/uniprot/SIR2_RAT", "http://www.uniprot.org/uniprot/SIR4_MOUSE", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D056564", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D056565", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D056566", "http://www.uniprot.org/uniprot/SIR1_MOUSE", "http://www.uniprot.org/uniprot/SIR2_MACFA" ]

[ "microRNAs (miRNAs), small nuclear RNAs (snRNAs), small nucleolar RNAs (snoRNAs) are the major classes of small non coding RNAs. Recently, thanks mostly to massively parallel sequencing technologies, other classes of small RNAs have been discovered, such as piRNAs and scaRNAs." ]

[ "miRNA", "snRNA", "snoRNAs", "scaRNAs", "piRNAS" ]

[ "Some of these RNA classes, in particular microRNAs and snoRNAs, undergo maturation processes that lead to the production of shorter RNAs." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/20823303", "http://www.ncbi.nlm.nih.gov/pubmed/19908360" ]

[]

[]

[ "People can help prevent kidney stones by making changes in fluid intake and, depending on the type of kidney stone, changes in consumption of sodium, animal protein, calcium, and oxalate.\nDrinking enough fluids each day is the best way to help prevent most types of kidney stones. Health care providers recommend that a person drink 2 to 3 liters of fluid a day. People with cystine stones may need to drink even more. Though water is best, other fluids may also help prevent kidney stones, such as citrus drinks." ]

[ "reducing sodium" ]

[ "calcium oxalate remains the dominant type accounting for 64% of stones in our dataset,", "Uric acid stones contributed 16% of contemporary stone compositions,", "Struvite stones showed a decreasing trend from 14% in the 1970s, to 12% in the 1980s and 7% in the current data.", ". Given recent concerns that calcium supplements may raise risk for cardiovascular disease and kidney stones," ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/23302672", "http://www.ncbi.nlm.nih.gov/pubmed/23438422", "http://www.ncbi.nlm.nih.gov/pubmed/23593205", "http://www.ncbi.nlm.nih.gov/pubmed/23880796", "http://www.ncbi.nlm.nih.gov/pubmed/23535174", "http://www.ncbi.nlm.nih.gov/pubmed/24127678", "http://www.ncbi.nlm.nih.gov/pubmed/22857835", "http://www.ncbi.nlm.nih.gov/pubmed/24026180", "http://www.ncbi.nlm.nih.gov/pubmed/16174292", "http://www.ncbi.nlm.nih.gov/pubmed/23221031", "http://www.ncbi.nlm.nih.gov/pubmed/23732207", "http://www.ncbi.nlm.nih.gov/pubmed/21369385", "http://www.ncbi.nlm.nih.gov/pubmed/23634702", "http://www.ncbi.nlm.nih.gov/pubmed/11269613", "http://www.ncbi.nlm.nih.gov/pubmed/23674806", "http://www.ncbi.nlm.nih.gov/pubmed/23568066", "http://www.ncbi.nlm.nih.gov/pubmed/23546565", "http://www.ncbi.nlm.nih.gov/pubmed/14552081", "http://www.ncbi.nlm.nih.gov/pubmed/23827660" ]

[ { "p": "http://linkedlifedata.com/resource/pubmed/keyword", "s": "http://linkedlifedata.com/resource/pubmed/id/13727389", "o": "http://linkedlifedata.com/resource/pubmed/keyword/KIDNEY+DISEASES%2Fnutrition+and+diet" }, { "p": "http://linkedlifedata.com/resource/pubmed/keyword", "s": "http://linkedlifedata.com/resource/pubmed/id/13688679", "o": "http://linkedlifedata.com/resource/pubmed/keyword/KIDNEY+DISEASES%2Fnutrition+and+diet" }, { "p": "http://linkedlifedata.com/resource/pubmed/keyword", "s": "http://linkedlifedata.com/resource/pubmed/id/13725651", "o": "http://linkedlifedata.com/resource/pubmed/keyword/KIDNEY+DISEASES%2Fnutrition+and+diet" }, { "p": "http://linkedlifedata.com/resource/pubmed/keyword", "s": "http://linkedlifedata.com/resource/pubmed/id/13688680", "o": "http://linkedlifedata.com/resource/pubmed/keyword/KIDNEY+DISEASES%2Fnutrition+and+diet" }, { "p": "http://linkedlifedata.com/resource/pubmed/keyword", "s": "http://linkedlifedata.com/resource/pubmed/id/13903830", "o": "http://linkedlifedata.com/resource/pubmed/keyword/KIDNEY+DISEASES%2Fnutrition+and+diet" }, { "p": "http://linkedlifedata.com/resource/pubmed/keyword", "s": "http://linkedlifedata.com/resource/pubmed/id/13816280", "o": "http://linkedlifedata.com/resource/pubmed/keyword/KIDNEY+DISEASES%2Fnutrition+and+diet" }, { "p": "http://linkedlifedata.com/resource/pubmed/keyword", "s": "http://linkedlifedata.com/resource/pubmed/id/13688678", "o": "http://linkedlifedata.com/resource/pubmed/keyword/KIDNEY+DISEASES%2Fnutrition+and+diet" } ]

[ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D007669", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D007668", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D014545", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D014676", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D007674", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004035", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D018753", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004032", "http://www.disease-ontology.org/api/metadata/DOID:585" ]

[ "Verapamil, a calcium channel blocker, is considered the mainstay of prophylactic therapy of Cluster Headache patients. Lithium carbonate, topiramate, valproic acid, gabapentin, baclofen, methysergide, melatonin, ketoprofen and indomethacin can also be tried for prophylactic therapy of Cluster Headaches patients. Non-pharmacological prophylactic measures, such as peripheral (mostly occipital nerve) and central (hypothalamic) neurostimulation, ablative surgery, and botulinum toxin type-A (BTX-A) injection, can be also considered." ]

[]

[ "The calcium channel blocker verapamil is the drug of choice for CH prevention. Other drugs that may be used for this purpose include lithium carbonate, topiramate, valproic acid, gabapentin, and baclofen.", "Recently, the therapeutic options for refractory CH patients have expanded with the emergence of both peripheral (mostly occipital nerve) and central (hypothalamic) neurostimulation.", "With the emergence of these novel treatments, the role of ablative surgery in CH has declined.", "The mainstay of prophylactic therapy is verapamil. Yet, other medications, including lithium, divalproex sodium, topiramate, methysergide, gabapentin, and even indomethacin, may be useful when the headache fails to respond to verapamil.", "For medically refractory patients, surgical interventions, occipital nerve stimulation, and deep brain stimulation remain an option.", "The objective of this open single-centre study was to evaluate the efficacy and tolerability of botulinum toxin type-A (BTX-A) as add-on in the prophylactic treatment of cluster headache (CH).", "These findings provide evidence that BTX-A may be beneficial as an add-on prophylactic therapy for a limited number of patients with chronic CH.", "There are a variety of different medications for abortive and prophylactic therapy, accompanied by a variable amount of evidence-based medicine.", "Most procedures are directed against the sensory trigeminal nerve and associated ganglia, eg, anesthetizing the sphenopalatine ganglion.", "The mainstay of prophylactic therapy is verapamil. Lithium, divalproex sodium, or topiramate may also be useful.", "Based on our clinical experience, we recommended the combination of nasal sumatriptan for acute attacks and verapamil 240 mg/day for prophylaxis.", "Topiramate also appears to be well tolerated and useful in the adjunctive treatment of cluster headache.", "The cornerstone of maintenance prophylaxis is verapamil, yet methysergide, lithium, and divalproex sodium may also be employed. In some patients, melatonin or topiramate may be useful adjunctive therapies.", "Prophylactic therapy in most cases consisted of verapamil, also with a good response.", "Patients with chronic cluster headache may achieve good results from long-term treatment with other therapies, including lithium carbonate, verapamil, and ketoprofen." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/11252143", "http://www.ncbi.nlm.nih.gov/pubmed/16628535", "http://www.ncbi.nlm.nih.gov/pubmed/15651299", "http://www.ncbi.nlm.nih.gov/pubmed/21284609", "http://www.ncbi.nlm.nih.gov/pubmed/17901920", "http://www.ncbi.nlm.nih.gov/pubmed/11026146", "http://www.ncbi.nlm.nih.gov/pubmed/2520442", "http://www.ncbi.nlm.nih.gov/pubmed/12390644", "http://www.ncbi.nlm.nih.gov/pubmed/20352587", "http://www.ncbi.nlm.nih.gov/pubmed/16041199" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D003027", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D055502" ]

[ "SR calcium uptake is mediated by a Ca(2+)-ATPase (SERCA2), whose activity is reversibly regulated by phospholamban (PLN). Dephosphorylated PLN is an inhibitor of SERCA and phosphorylation of PLN relieves this inhibition. Phospholamban (PLN) is a small integral membrane protein, which binds and inhibits in a yet unknown fashion the Ca(2+)-ATPase (SERCA) in the sarcoplasmic reticulum. Based on structural and dynamics data, a model in which PLN undergoes allosteric activation upon encountering SERCA has been proposed. The allosteric regulation of SERCA depends on the conformational equilibrium of PLN, whose cytoplasmic regulatory domain interconverts between three different states: a ground T state (helical and membrane associated), an excited R state (unfolded and membrane detached), and a B state (extended and enzyme-bound), which is noninhibitory. Phosphorylation of PLN shifts the populations toward the B state, increasing SERCA activity. Phospholamban (PLN) regulates cardiac contractility via its modulation of sarco(endo)plasmic reticulum calcium ATPase (SERCA) activity. Impairment of this regulatory process causes heart failure." ]

[]

[ "Phospholamban (PLN) is a small integral membrane protein, which binds and inhibits in a yet unknown fashion the Ca(2+)-ATPase (SERCA) in the sarcoplasmic reticulum.", "SR calcium uptake is mediated by a Ca(2+)-ATPase (SERCA2), whose activity is reversibly regulated by phospholamban (PLN). Dephosphorylated PLN is an inhibitor of SERCA and phosphorylation of PLN relieves this inhibition. ", "Regulation of the SERCA calcium pump by phospholamban (PLB) is largely due to interactions between their respective transmembrane domains. In spite of numerous mutagenesis and kinetic studies, we still do not have a clear mechanistic picture of how PLB influences the calcium transport cycle of SERCA. ", "Phospholamban (PLN) regulates cardiac contractility via its modulation of sarco(endo)plasmic reticulum calcium ATPase (SERCA) activity. Impairment of this regulatory process causes heart failure.", "Based on structural and dynamics data, we propose a model in which PLN undergoes allosteric activation upon encountering SERCA.", "The membrane protein complex between the sarcoplasmic reticulum Ca(2+)-ATPase (SERCA) and phospholamban (PLN) controls Ca(2+) transport in cardiomyocytes, thereby modulating cardiac contractility. β-Adrenergic-stimulated phosphorylation of PLN at Ser-16 enhances SERCA activity via an unknown mechanism.", "We found that the allosteric regulation of SERCA depends on the conformational equilibrium of PLN, whose cytoplasmic regulatory domain interconverts between three different states: a ground T state (helical and membrane associated), an excited R state (unfolded and membrane detached), and a B state (extended and enzyme-bound), which is noninhibitory. Phosphorylation at Ser-16 of PLN shifts the populations toward the B state, increasing SERCA activity.", "Phospholamban (PLN) is a type II membrane protein that inhibits the sarcoplasmic reticulum Ca(2+)-ATPase (SERCA), thereby regulating calcium homeostasis in cardiac muscle." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/23308118", "http://www.ncbi.nlm.nih.gov/pubmed/15781867", "http://www.ncbi.nlm.nih.gov/pubmed/22679139", "http://www.ncbi.nlm.nih.gov/pubmed/24101520", "http://www.ncbi.nlm.nih.gov/pubmed/21576492", "http://www.ncbi.nlm.nih.gov/pubmed/19708671" ]

[]

[ "http://www.uniprot.org/uniprot/AT2A_CHIOP", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D053498" ]

[ "Mammalian target of rapamycin complex 2 (mTORC2) is a kinase complex comprised of mTOR, Rictor, mSin1, mLST8/GβL and PRR5." ]

[ "mTOR", "Rictor", "mSin1", "mLST8/GβL", "PRR5" ]

[ "mTOR is the major component of two protein complexes: mTOR complex 1 (mTORC1) and mTORC2", " Rictor, an mTORC2-specific component", "f Rictor (rapamycin-insensitive companion of mTOR), an mTORC2 component,", " The mammalian target of rapamycin (mTOR) complex 2 (mTORC2), which contains the regulatory protein Rictor (rapamycin-insensitive companion of mTOR), ", " Rictor, a key component of mTORC2", "SIN1, a key component of mTOR complex 2 (mTORC2)", " the essential mTORC2 component rictor ", "Sin1 is an essential component of mTOR complex 2 (mTORC2). ", " SIN1 or Rictor, two key components of mTOR complex 2 (mTORC2)", " Mammalian target of rapamycin complex 2 (mTORC2) is a kinase complex comprised of mTOR, Rictor, mSin1, mLST8/GβL and PRR5 " ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/23455608", "http://www.ncbi.nlm.nih.gov/pubmed/22820188", "http://www.ncbi.nlm.nih.gov/pubmed/22595285", "http://www.ncbi.nlm.nih.gov/pubmed/22773877", "http://www.ncbi.nlm.nih.gov/pubmed/23049074", "http://www.ncbi.nlm.nih.gov/pubmed/22532249", "http://www.ncbi.nlm.nih.gov/pubmed/24077282", "http://www.ncbi.nlm.nih.gov/pubmed/23673367", "http://www.ncbi.nlm.nih.gov/pubmed/22678916", "http://www.ncbi.nlm.nih.gov/pubmed/24244675" ]

[ { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A10789460", "o": "C39159" }, { "p": "http://linkedlifedata.com/resource/umls/prefMetaMap", "s": "http://linkedlifedata.com/resource/umls/id/C1515673", "o": "http://linkedlifedata.com/resource/umls/label/A7667725" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A7667725", "o": "mTOR Signaling Pathway" }, { "p": "http://www.w3.org/2008/05/skos-xl#prefLabel", "s": "http://linkedlifedata.com/resource/umls/id/C1515673", "o": "http://linkedlifedata.com/resource/umls/label/A7667725" }, { "p": "http://linkedlifedata.com/resource/umls/altMetaMap", "s": "http://linkedlifedata.com/resource/umls/id/C1515673", "o": "http://linkedlifedata.com/resource/umls/label/A10789460" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A7667725", "o": "C39159" } ]

[ "http://www.uniprot.org/uniprot/MTOR_MOUSE", "http://www.uniprot.org/uniprot/MTOR_HUMAN", "http://www.uniprot.org/uniprot/MTOR_RAT", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0070438" ]

[ "Digit ratio (2D:4D) is associated with gastric cancer, prostate cancer, breast cancer, cervical intraepithelial neoplasia and oral squamous cell carcinoma. 2D:4D was found to be higher in patients diagnosed with gastric cancer and prostate cancer patients relative to controls. Among prostate cancer patients, 2D:4D shows strong differences between African-Americans and Caucasians; however, it does not correlate with disease severity in men already diagnosed with prostate cancer. However, other authors did not find an association between 2D:4D and prostate cancer risk.\n 2D:4D is not associated with testicular germ cell tumors." ]

[]

[ "RESULTS: Right 2D:4D was not associated with TGCT [odds ratio (OR) for a one-standard deviation (SD) increase in right-hand 2D:4D: 1.12, 95% confidence interval (CI): 0.93-1.34]. The results were consistent when evaluating the association based on the left hand. The difference between right and left-hand 2D:4D was also not associated with TGCT risk [OR for a one-SD increase in ΔR-L: 1.03, 95% CI: 0.87-1.23]. ", "Digit ratio (2D:4D) is associated with gastric cancer.", "RESULTS: GCA group presented significantly higher left 2D:4D, but significantly lower R-L in comparison to healthy controls, particularly so for males. Digit ratio did not correlate to clinical staging or TNM staging.", "The 2D:4D pattern found for gastric cancer parallels that earlier described for breast cancer.", "Higher second fourth digit ratio predicts higher incidence of prostate cancer in prostate biopsy.", "2D/4D ratio >0,95 (OR (CI 95%) 4,4 (1,491-13,107) was related to neoplasia. ", "CONCLUSION: High digit ratio predicts PCa in men undergoing prostate biopsy. Digit ratio >0,95 has 4-fold risk of PCa compared to men with digit ratio ≤0.95.", "RESULTS: African-American men with prostate cancer are 3.70 times more likely to have a low 2D:4D digit ratio than Caucasian men with prostate cancer (95% confidence interval: 1.98, 6.92; P < 0.0001). There were no statistically significant differences in the presence of metastasis, Gleason score, family history or age at diagnosis by digit ratio. CONCLUSION: 2D:4D ratio shows strong differences between African-Americans and Caucasians; however, it does not correlate with disease severity in men already diagnosed with prostate cancer. ", "RESULTS: We found a direct association between left 2D:4D and breast cancer risk, an inverse association between Δ(r-l) and risk of breast cancer, but no association between right 2D:4D and breast cancer risk. Among breast cancer cases, both right 2D:4D and Δ(r-l) were inversely associated with age at diagnosis.", "CONCLUSION: Digit ratio measures might be associated with breast cancer risk and age at onset of breast cancer.", "Recent studies have reported a strong association between 2D:4D and risk of prostate cancer. ", "RESULTS: No association was observed between 2D:4D and prostate cancer risk overall (HRs 1.00; 95% CIs, 0.92-1.08 for right, 0.93-1.08 for left). ", "CONCLUSION: Our results are not consistent with an association between 2D:4D and overall prostate cancer risk, but we cannot exclude a weak inverse association between 2D:4D and early onset prostate cancer risk.", "Males in the OSCC group presented significantly higher digit ratio (P = 0.03) in comparison with males with OPLs and individuals without oral lesions. CONCLUSIONS: According to the results, males with the higher digit ratio seem to be more prone to undergo malignization of lesions in the oral cavity. ", "Compared with index finger shorter than ring finger (low 2D : 4D), men with index finger longer than ring finger (high 2D : 4D) showed a negative association, suggesting a protective effect with a 33% risk reduction (odds ratio (OR) 0.67, 95% confidence interval (CI) 0.57-0.80). Risk reduction was even greater (87%) in age group <60 (OR 0.13, 95% CI 0.09-0.21). CONCLUSION: Pattern of finger lengths may be a simple marker of prostate cancer risk, with length of 2D greater than 4D suggestive of lower risk.", "In the case-control analysis (n = 263), after controlling for ethnicity, women who developed CIN were significantly more likely to have a higher 2D:4D compared with HPV-negative women. A similar, nonsignificant trend was observed among women with a persistent HPV infection. CONCLUSION: Lower fetal androgen exposure may predispose to persistent HPV and increased risk of CIN.", "Low numbers of CAG repeats and low 2D:4D are both associated with high sperm numbers and protection against breast cancer. ", "Digit ratio measures might be associated with breast cancer risk and age at onset of breast cancer.", "A lower digit ratio is related to an increased detection rate of prostate cancer, a high percentage of core cancer volume and a high Gleason score.", " Digit ratio could act as a possible marker for cancer predisposition.", "Right hand digit ratio (2D:4D) is associated with oral cancer.", "CONCLUSION: Digit ratio measures might be associated with breast cancer risk and age at onset of breast cancer.", "Second to fourth digit ratio: a predictor of prostate-specific antigen level and the presence of prostate cancer.", "CONCLUSIONS: Patients with a lower digit ratio have higher risks of prostate biopsy and prostate cancer.", "Second and fourth digit ratio has also found to be correlated with sexual orientation, left hand preference autism and some adult onset diseases such as breast cancer and myocardial infarction.", "Low numbers of CAG repeats and low 2D:4D are both associated with high sperm numbers and protection against breast cancer.", "Findings from AR studies predict that low 2D:4D will be associated with prostate and hepatocellular cancer, urolithiasis, ADHD, ankylosing spondylitis, spontaneous abortion, and polycystic ovaries, while high 2D:4D will be associated with motor neuron diseases and endometrial cancer.", "We found a direct association between left 2D:4D and breast cancer risk, an inverse association between Δ(r-l) and risk of breast cancer, but no association between right 2D:4D and breast cancer risk", "Digit ratio measures might be associated with breast cancer risk and age at onset of breast cancer", "The 2D:4D pattern found for gastric cancer parallels that earlier described for breast cancer" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/23146972", "http://www.ncbi.nlm.nih.gov/pubmed/24677324", "http://www.ncbi.nlm.nih.gov/pubmed/21119657", "http://www.ncbi.nlm.nih.gov/pubmed/12208164", "http://www.ncbi.nlm.nih.gov/pubmed/18203126", "http://www.ncbi.nlm.nih.gov/pubmed/23154605", "http://www.ncbi.nlm.nih.gov/pubmed/22990654", "http://www.ncbi.nlm.nih.gov/pubmed/20633006", "http://www.ncbi.nlm.nih.gov/pubmed/23218867", "http://www.ncbi.nlm.nih.gov/pubmed/23623693", "http://www.ncbi.nlm.nih.gov/pubmed/23131519", "http://www.ncbi.nlm.nih.gov/pubmed/21730975", "http://www.ncbi.nlm.nih.gov/pubmed/12441204", "http://www.ncbi.nlm.nih.gov/pubmed/21445935" ]

[]

[ "http://www.disease-ontology.org/api/metadata/DOID:162" ]

[ "A rare variant of the TREM2 gene, which encodes the triggering receptor encoded in myeloid cells 2 (rs75932628-T) causing a R47H substitution has been associated with both early and late onset Alzheimer's disease in various populations. Emerging evidence has demonstrated that TREM2 could suppress inflammatory response by repression of microglia-mediated cytokine production and secretion, which may prevent inflammation-induced bystander damage of neurons. Higher levels of TREM2 mRNA (p = 0.002) and protein (p < 0.001) were identified in AD patients which indicates that TREM2 might serve as a novel noninvasive biomarker for AD diagnosis. Based on the potential protective actions of TREM2 in AD pathogenesis, targeting TREM2 might provide new opportunities for AD treatment." ]

[ "yes" ]

[ "Absence of TREM2 polymorphisms in patients with Alzheimer's disease and Frontotemporal Lobar Degeneration", " These data demonstrate that TREM2 coding region is highly conserved, implying a crucial role of this receptor. Further studies, including a functional analysis, are certainly required to clarify the role of TREM2 in neurodegenerative processes", "Moreover, a rare TREM2 exon 2 variant (p.R47H) was reported to increase the risk of Alzheimer's disease (AD) with an odds ratio as strong as that for APOEε4", "We observed an enrichment of rare variants across TREM2 in both AD and FTD patients compared to controls, most notably in the extracellular IgV-set domain", "None of the rare variants individually reached significant association, but the frequency of p.R47H was increased ~ 3-fold in both AD and FTD patients compared to controls, in line with previous reports", "Our data corroborate and extend previous findings to include an increased frequency of rare heterozygous TREM2 variations in AD and FTD, and show that TREM2 variants may play a role in neurodegenerative diseases in general.", "non-synonymous genetic rare variant, rs75932628-T (p.R47H), in the TREM2 gene has recently been reported to be a strong genetic risk factor for Alzheimer's disease (AD)", "These data strongly support the important role of p.R47H in AD risk, and suggest that this rare genetic variant is not related to FTD.", " Higher levels of TREM2 mRNA (p = 0.002) and protein (p < 0.001) were identified in AD patients", "Our results indicate that TREM2 might serve as a novel noninvasive biomarker for AD diagnosis", "studies have identified the rs75932628 (R47H) variant in TREM2 as an Alzheimer's disease risk factor with estimated odds ratio ranging from 2.9 to 5.1", "This study replicates the association between R47H and Alzheimer's disease risk in a large, population-based sample, and estimates the population frequency and attributable risk of this rare variant", "Moreover, mutation scanning of the five exons of TREM2 failed to detect the presence of novel polymorphisms", "A rare missense mutation (rs75932628-T) in the gene encoding the triggering receptor expressed on myeloid cells 2 (TREM2), which was predicted to result in an R47H substitution, was found to confer a significant risk of Alzheimer's disease in Iceland", "We also found that carriers of rs75932628-T between the ages of 80 and 100 years without Alzheimer's disease had poorer cognitive function than noncarriers", "Our findings strongly implicate variant TREM2 in the pathogenesis of Alzheimer's disease. Given the reported antiinflammatory role of TREM2 in the brain, the R47H substitution may lead to an increased predisposition to Alzheimer's disease through impaired containment of inflammatory processes", "rs75932628-T variant of the gene encoding the triggering receptor expressed on myeloid cells 2 (TREM2) has recently been identified as a rare risk factor for late-onset Alzheimer's disease (AD)", "These results confirm the association between this variant and AD and underline its involvement in early-onset cases", "recent studies have reported the association of rs75932628-T in the TREM2 gene with the risk for Alzheimer's disease (AD)", "Rs75932628-T is a rare nonsynonymous variant (p.R47H) that confers a high risk of AD with an effect size similar to that of the APOE ɛ4 allele", "Here, we report the first positive replication study in a Spanish population and confirm that TREM2 rs75932628-T is associated with the risk for AD", "works have demonstrated a rare functional variant (R47H) in triggering receptor expressed on myeloid cells (TREM) 2 gene, encoding TREM2 protein, increase susceptibility to late-onset Alzheimer's disease (AD), with an odds ratio similar to that of the apolipoprotein E ε4 allele", "The reduced function of TREM2 was speculated to be the main cause in the pathogenic effects of this risk variant, and TREM2 is highly expressed in white matter, as well as in the hippocampus and neocortex, which is partly consistent with the pathological features reported in AD brain, indicating the possible involvement of TREM2 in AD pathogenesis", "Emerging evidence has demonstrated that TREM2 could suppress inflammatory response by repression of microglia-mediated cytokine production and secretion, which may prevent inflammation-induced bystander damage of neurons", "TREM2 also participates in the regulation of phagocytic pathways that are responsible for the removal of neuronal debris", "Based on the potential protective actions of TREM2 in AD pathogenesis, targeting TREM2 might provide new opportunities for AD treatment", "Under the hypothesis that low-prevalence variants showing moderate-to-high effect size may be associated with risk for sAD, two independent research groups have demonstrated that a rare variant (rs75932628, encoding a substitution of arginine by histidine at residue 47 (R47H), in the TREM2 gene, which encodes the triggering receptor expressed on myeloid cells 2) is significantly associated with an increased susceptibility to sAD", "Recently, a novel variant in the gene encoding the triggering receptor expressed on myeloid cells 2 (TREM2) has been identified that has refocused the spotlight back onto inflammation as a major contributing factor in AD", "TREM gene cluster, a region recently reported to harbor rare variants that increase AD risk", "evidence suggests that rare genetic variants within the TREM2 gene are associated with increased risk of Alzheimer's disease", "These data suggest that a mutational burden in TREM2 may serve as a risk factor for neurodegenerative disease in general, and that potentially this class of TREM2 variant carriers with dementia should be considered as having a molecularly distinct form of neurodegenerative disease", "The association of TREM2 variants with AD brings innate immune signaling into the light, affirming innate immunity's role as a significant factor in AD pathogenesis", "The purpose of this paper is to discuss these recent developments including the potential role that TREM2 normally plays and how loss of function may contribute to AD pathogenesis by enhancing oxidative stress and inflammation within the CNS", "Even though we are more at the beginning than at the end of sAD genetics, there is some reason for optimism given the recent identification of novel risk or protective variants (such as rare TREM2 and APP mutations) showing strong statistical associations with sAD" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/23855982", "http://www.ncbi.nlm.nih.gov/pubmed/23391427", "http://www.ncbi.nlm.nih.gov/pubmed/24041969", "http://www.ncbi.nlm.nih.gov/pubmed/23582655", "http://www.ncbi.nlm.nih.gov/pubmed/23562540", "http://www.ncbi.nlm.nih.gov/pubmed/23150908", "http://www.ncbi.nlm.nih.gov/pubmed/17088018", "http://www.ncbi.nlm.nih.gov/pubmed/23692967", "http://www.ncbi.nlm.nih.gov/pubmed/23510020", "http://www.ncbi.nlm.nih.gov/pubmed/23407992", "http://www.ncbi.nlm.nih.gov/pubmed/23380991", "http://www.ncbi.nlm.nih.gov/pubmed/24002183", "http://www.ncbi.nlm.nih.gov/pubmed/24119542", "http://www.ncbi.nlm.nih.gov/pubmed/23533697" ]

[]

[ "http://www.uniprot.org/uniprot/TREM2_HUMAN", "http://www.uniprot.org/uniprot/TREM2_MOUSE", "http://www.disease-ontology.org/api/metadata/DOID:10652", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D000544" ]

[ "mammalian target of rapamycin (mTOR) is a major negative regulator of autophagy." ]

[ "yes" ]

[ "autophagy is negatively regulated by the mammalian target of rapamycin receptor (mTOR)", "Subjecting cells to starvation or rapamycin efficiently induces autophagy by inhibiting the MTOR signaling pathway triggering increased autophagic flux. ", "Several pathways, including mTOR, have been shown to regulate autophagy.", "these results provide insights into the mechanism by which hyperactivation of mTORC1 promotes breast cancer progression through increasing autophagy and Akt activation in vivo.", " the canonical mTOR-controlled autophagy pathway", "mTOR inhibition severely impairs liver regeneration and increases autophagy after PH", "mTOR remains at a high level and inhibits autophagy.", "AKT is involved in granulosa cell autophagy regulation via mTOR signaling during rat follicular development and atresia.", "mammalian target of rapamycin (mTOR), a major negative regulator of autophagy.", "mTOR suppresses granulosa cell autophagy", "Mammalian target of rapamycin (mTOR), a potent suppressor of autophagy,", "The mTOR signaling pathway integrates inputs from a variety of upstream stimuli to regulate diverse cellular processes including proliferation, growth, survival, motility, autophagy, protein synthesis and metabolism", "The activation of mammalian target of rapamycin (mTOR) signaling pathway blocks the effects of ghrelin-induced autophagy and apoptosis,", " inducing apoptosis and autophagy via the mTOR signaling pathway", " The mTOR gene regulates cell growth by controlling mRNA translation, ribosome biogenesis, autophagy, and metabolism." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/24275666", "http://www.ncbi.nlm.nih.gov/pubmed/24209762", "http://www.ncbi.nlm.nih.gov/pubmed/23940798", "http://www.ncbi.nlm.nih.gov/pubmed/24265855", "http://www.ncbi.nlm.nih.gov/pubmed/24024901", "http://www.ncbi.nlm.nih.gov/pubmed/24255881", "http://www.ncbi.nlm.nih.gov/pubmed/24275748", "http://www.ncbi.nlm.nih.gov/pubmed/24092929", "http://www.ncbi.nlm.nih.gov/pubmed/24131573", "http://www.ncbi.nlm.nih.gov/pubmed/23982275", "http://www.ncbi.nlm.nih.gov/pubmed/24278483", "http://www.ncbi.nlm.nih.gov/pubmed/24326530" ]

[ { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A10789460", "o": "C39159" }, { "p": "http://linkedlifedata.com/resource/umls/prefMetaMap", "s": "http://linkedlifedata.com/resource/umls/id/C1515673", "o": "http://linkedlifedata.com/resource/umls/label/A7667725" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A7667725", "o": "mTOR Signaling Pathway" }, { "p": "http://www.w3.org/2008/05/skos-xl#prefLabel", "s": "http://linkedlifedata.com/resource/umls/id/C1515673", "o": "http://linkedlifedata.com/resource/umls/label/A7667725" }, { "p": "http://linkedlifedata.com/resource/umls/altMetaMap", "s": "http://linkedlifedata.com/resource/umls/id/C1515673", "o": "http://linkedlifedata.com/resource/umls/label/A10789460" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A7667725", "o": "C39159" } ]

[ "http://www.uniprot.org/uniprot/MTOR_MOUSE", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0010508", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001343", "http://www.uniprot.org/uniprot/MTOR_HUMAN", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0010506", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0006914", "http://www.uniprot.org/uniprot/MTOR_RAT", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0010507" ]

[ "Metabolic syndrome is a disorder of energy utilization and storage, diagnosed by a co-occurrence of three out of five of the following medical conditions: abdominal (central) obesity, elevated blood pressure, elevated fasting plasma glucose, high serum triglycerides, and low high-density cholesterol (HDL) levels. Metabolic syndrome increases the risk of developing cardiovascular disease, particularly heart failure, and diabetes." ]

[ "Obesity", "High blood pressure", "Hypertension", "High serum triglycerides", "Low high-density cholesterol (HDL) levels", "Diabetes type 2", "Dyslipidaemia" ]

[ "tigated the association between circulating levels of 60 and 70 kDa heat-shock proteins (HSP60 and 70) and cardiovascular risk factors in postmenopausal women with or without metabolic syndrome (MetS). This cross-sectional study included 311 Brazilian women (age ≥45 years with amenorrhea ≥12 months). Women showing three or more of the following diagnostic criteria were diagnosed with MetS: waist circumference (WC) ≥88 cm, blood pressure ≥130/85 mmHg, triglycerides ≥150 mg/dl, high-density lipoprotein (HDL) <50 mg/dl, and glucose ≥100 mg/dl. Clinical, anthropometric, and biochemical parameters were collected. HSP60, HSP70, antibodies to HSP60 and HSP70, and C-reactive protein (CRP) levels were measured in serum. Student's t test, Kruskal-Wallis test, chi-square test, and Pearson correlation were used for statistical analysis. Of the 311 women, 30.9 % (96/311) were diagnosed with MetS. These women were, on average, obese with abdominal fat deposition and had lower HDL values as well as higher triglycerides and glucose levels. Homeostasis model assessment-insulin resistant (HOMA-IR) test values in these women were compatible with insulin resistance (P < 0.05). CRP and ", " is associated with an increased risk for cardiovascular disease (CVD) and type 2 diabetes mellitus (T2DM). Several", "alence of the metabolic syndrome (MetS), a cluster of cardiovascular risk factors associated with obesity and insulin resistance, is dramatically increasing in Western and developing countries. This disorder is not only associated with a higher risk of appearance of type 2 diabetes and cardiovascular events, but impacts on the liver in different ways. Nonalc", "bolic syndrome (MS) components, such as dyslipidemia, prothrombotic status, and increased blood pressure, are risk factors for patients with renal disease. Visceral fat mass is closely related to the MS and atherosclerosis. We investigated the effects of body compositions and MS on anemia parameters and recombinant human erythropoietin (rHuEPO) requirements in maintenance hemodialysis patients. METHODS: Body composition (body mass index and bioimpedance analysis) and laboratory data were obtained from 110 dialysis patients. The MS was identified according to ATP-III criteria. Anemia parameters, hemoglobin (Hgb), albumin, C-reactive protein (CRP), calcium, phosphorus, parathormone levels, and rHuEPO requirements over the last 6 months were retrospectively analyzed. RESULTS: Patients with the MS seem to reach target Hgb levels more frequently (10-12 g/dL; 66.3% vs 84.8%; P = .03) without any difference in total intravenous iron therapy dosage. MS patients also required lower rHuEPO for reaching similar Hgb levels compared with patients without MS (2679.3 ± 1936.1 vs 3702.5 ± 2213.0 U/kg/6 mo; P = .02). There we", "bolic syndrome (MetS) is typically diagnosed based on abnormalities in specific clustered clinical measures that are associated with increased risk for coronary heart disease (CHD) and Type 2 diabetes mellitus (T2DM). However, current MetS criteria result in racial/ethnic discrepancies. Our goals were to use confirmatory factor analysis (CFA) to delineate differential contributions to MetS by sub-group, and if contributions were discovered, develop sex and racial/ethnic-specific equations to calculate MetS severity. RESEARCH DESIGN AND METHODS: Using data on adults from the National Health and Nutrition Examination Survey 1999-2010, we performed a CFA of a single MetS factor that allowed differential loadings across groups, resulting in a sex and race/ethnicity-specific continuous MetS severity score. RESULTS: Loadings to the single MetS factor differed by sub-group for each MetS component (p<0.001), with lower factor loadings among non-Hispanic-blacks for triglycerides and among Hispanics for waist circumference. Systolic blood pressure exhibited low factor loadings among all groups. MetS severity scores were correlated with biomarkers of future disease (high-sensitivity C-reactive-protein, uric acid, insulin resistance). Non-Hispanic-black-males with diabetics had a low prevalence of MetS but high MetS severity scores that were not significantly different from other racial/ethnic groups. CONCLUSIONS: This analysis among adults uniquely demonstrated differences between sexes and racial/ethnic groups regarding contributions of traditional MetS components to an assumed single factor. The resulting equations provide a clinically-accessible and interpretable continuous measure of MetS for potential use in identifying adults at higher risk for MetS-related diseases and following changes within individuals over time. These eq", " study, we aim to examine the associations of obesity related loci with risk of metabolic syndrome (MetS) in a children population from China. A tota", "alence of obesity is on the increase, and consequently metabolic syndrome is also becoming a serious health problem in children and adolescents all over the world. This rev", "ciation between alopecia areata (AA), psoriasis, and other autoimmune diseases has been well reported in the literature, an association with metabolic syndrome has not been reported. We present two young women with the combination of severe psoriasis, androgen excess, metabolic syndrome, thyroiditis, and AA. Both w" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/21448316", "http://www.ncbi.nlm.nih.gov/pubmed/24290837", "http://www.ncbi.nlm.nih.gov/pubmed/24227418", "http://www.ncbi.nlm.nih.gov/pubmed/24308220", "http://www.ncbi.nlm.nih.gov/pubmed/24320032", "http://www.ncbi.nlm.nih.gov/pubmed/24320038", "http://www.ncbi.nlm.nih.gov/pubmed/24269186", "http://www.ncbi.nlm.nih.gov/pubmed/24247648", "http://www.ncbi.nlm.nih.gov/pubmed/24277673", "http://www.ncbi.nlm.nih.gov/pubmed/24203651", "http://www.ncbi.nlm.nih.gov/pubmed/24152591", "http://www.ncbi.nlm.nih.gov/pubmed/24314947", "http://www.ncbi.nlm.nih.gov/pubmed/24287796", "http://www.ncbi.nlm.nih.gov/pubmed/24313546", "http://www.ncbi.nlm.nih.gov/pubmed/24326560", "http://www.ncbi.nlm.nih.gov/pubmed/24295929", "http://www.ncbi.nlm.nih.gov/pubmed/23093663", "http://www.ncbi.nlm.nih.gov/pubmed/18793503", "http://www.ncbi.nlm.nih.gov/pubmed/24309486", "http://www.ncbi.nlm.nih.gov/pubmed/24274871", "http://www.ncbi.nlm.nih.gov/pubmed/24327239", "http://www.ncbi.nlm.nih.gov/pubmed/18931101", "http://www.ncbi.nlm.nih.gov/pubmed/24314937", "http://www.ncbi.nlm.nih.gov/pubmed/24305580", "http://www.ncbi.nlm.nih.gov/pubmed/16855517", "http://www.ncbi.nlm.nih.gov/pubmed/24191289" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D024821", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D008659", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D008660" ]

[ "Multiple kinase inhibitors used in cancer therapy include ZD6474, SU11248, AEE 788, sorafenib, vatalanib, and AG-013736." ]

[ "ZD6474", "SU11248", "AEE 788", "sorafenib", "vatalanib", "AG-013736" ]

[ "These inhibitors generally hinder the phosphorylation of several protein kinases of membrane receptors, such as vascular endothelial growth factor receptors, platelet-derived growth factor receptors, the human epidermal growth factor receptor family, and cytoplasmic receptors such as c-Kit, Raf kinase, and FLT3.", "These inhibitors include ZD6474, SU11248, AEE 788, sorafenib, vatalanib, and AG-013736." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/16159418" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004358", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009369", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0033673", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011494", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D047428", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013812", "http://www.disease-ontology.org/api/metadata/DOID:162" ]

[ "Yes, proteomics has been used in the study of Pick's disease." ]

[ "yes" ]

[ "In Pick's disease, increased AGE, CML, CEL, HNE and MDAL bands of about 50 kDa were observed in the frontal cortex (but not in the occipital cortex) in association with increased density of glial acidic protein bands.", "Thus, brain and cerebrospinal fluid (CSF) samples from patients with Alzheimer's disease, Down syndrome, Pick's disease, Parkinson's disease, schizophrenia, and other disorders as well as brain and CSF from animals serving as models of neurological disorders have been analyzed by proteomics. ", "The present study is designed to investigate expression of peroxiredoxins (Prxs), the newly characterized family of highly conserved antioxidant enzymes, and other antioxidant enzymes in frontal cortex and cerebellum of DS, AD and PD patients using the technique of proteomics. ", "HMT levels were measured in the frontal cortex and cerebellum of brains of patients with AD, DS, and PiD, and normal aged subjects using proteomics techniques. " ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/11880199", "http://www.ncbi.nlm.nih.gov/pubmed/16987245", "http://www.ncbi.nlm.nih.gov/pubmed/16555340", "http://www.ncbi.nlm.nih.gov/pubmed/12650976" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D020543", "http://www.disease-ontology.org/api/metadata/DOID:4", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D040901", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D057180", "http://www.disease-ontology.org/api/metadata/DOID:11870", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D020774" ]

[ "Bladder cancer is any of several types of malignancy arising from the epithelial lining of the urinary bladder. Rarely the bladder is involved by non-epithelial cancers, such as lymphoma or sarcoma. It is a disease in which abnormal cells multiply without control in the bladder.The bladder is a hollow, muscular organ that stores urine; it is located in the pelvis. The most common type of bladder cancer recapitulates the normal histology of the urothelium and is known as transitional cell carcinoma or more properly urothelial cell carcinoma. It is estimated that there are 383,000 cases of bladder cancer worldwide", "Yes, there are. Urine biomarkers for bladder cancer diagnosis range from voided urine cytology and the UroVysion® cytogenetic test, to fluorescence in situ hybridisation (FISH), ImmunoCyt, NMP22, Bladder Tumor Antigen, BLCA-1, BLCA-4, hyaluronic acid, hyaluronidase, Lewis X antigen, microsatellite analysis, Quanticyt, soluble Fas, Survivin, telomerase, IL-8, MMP-9 and 10, PAI-1, VEGF, ANG, CA9 and APOE." ]

[ "yes" ]

[ "CONCLUSIONS: Several gene-based urinary biomarkers have demonstrated promise in initial studies, which now need to be rigorously validated in the clinical setting for them to be translated into clinically useful tests in diagnosis, surveillance or risk-stratification of bladder cancer", " Novel promising markers are in various stages of clinical testing, and a panel of biomarkers may serve in the future as a feasible alternative to urine cytology and cystoscopy for the screening, detection, and follow-up of non-muscle invasive bladder cancer.", "RESULTS: Seven of the 8 urine biomarkers were increased in subjects with bladder cancer relative to those without bladder cancer. The 7 biomarkers were assessed in a new model, which had an AUROC of 0.88 (95% CI 0.84-0.93), and 74% sensitivity and 90% specificity.", "The study provides further evidence that the reported panel of diagnostic biomarkers can reliably achieve the noninvasive detection of bladder cancer with higher sensitivity than currently available urine based assays.", "The urinary concentrations of 14 biomarkers (IL-8, MMP-9, MMP-10, SDC1, CCL18, PAI-1, CD44, VEGF, ANG, CA9, A1AT, OPN, PTX3, and APOE) were assessed by enzyme-linked immunosorbent assay (ELISA). Diagnostic performance of each biomarker and multivariate models were compared using receiver operating characteristic curves and the chi-square test. An 8-biomarker model achieved the most accurate BCa diagnosis (sensitivity 92%, specificity 97%), but a combination of 3 of the 8 biomarkers (IL-8, VEGF, and APOE) was also highly accurate (sensitivity 90%, specificity 97%). For comparison, the commercial BTA-Trak ELISA test achieved a sensitivity of 79% and a specificity of 83%, and voided urine cytology detected only 33% of BCa cases in the same cohort. These data show that a multivariate urine-based assay can markedly improve the accuracy of non-invasive BCa detection", ": Histopathological grading of papillary urothelial tumors (PUTs) of the urinary bladder is subjective and poorly reproducible. We investigated the relationship between the expression of frequently deregulated microRNAs (miRNAs) as well as their target genes (ZEB1/ZEB2) and bladder cancer histopathological grade in an attempt to find a miRNA that might allow more reliable grading of PUTs.", "The Mcm5 immunoassay is a non-invasive test for identifying patients with urothelial cancers with similar accuracy to the FDA-approved NMP22 ELISA Test Kit. The combination of Mcm5 plus NMP22 improves the detection of UCC and identifies 95% of clinically significant disease. Trials of a commercially developed Mcm5 assay suitable for an end-user laboratory alongside NMP22 are required to assess their potential clinical utility in improving diagnostic and surveillance care pathways.", "HYAL-1 and HAS1 expression predicted BCa metastasis, and HYAL-1 expression also predicted disease-specific survival. Furthermore, the combined HAS2-HYAL-1 biomarker detected BCa and significantly predicted its recurrence.", "Cancer biomarkers are the backbone for the implementation of individualized approaches to bladder cancer (BCa). ", "Through genomic and proteomic profiling of urine, we have identified a panel of biomarkers associated with the presence of BCa. In this study, we evaluated the utility of three of these biomarkers, interleukin 8 (IL-8), Matrix metallopeptidase 9 (MMP-9) and Syndecan in the diagnosis of BCa through urinalysis. METHODS: Voided urines from 127 subjects, cancer subjects (n = 64), non-cancer subjects (n = 63) were analyzed. The protein concentrations of IL-8, MMP-9, and Syndecan were assessed by enzyme-linked immunosorbent assay (ELISA).", ". There was an association between differences in individual biomarkers and differences in protein levels over time, particularly in control patients. Collectively, our findings identify caveats intrinsic to the common practice of protein standardization in biomarker discovery studies conducted on urine, particularly in patients with hematuria" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/24139504", "http://www.ncbi.nlm.nih.gov/pubmed/24578952", "http://www.ncbi.nlm.nih.gov/pubmed/22559832", "http://www.ncbi.nlm.nih.gov/pubmed/24183881", "http://www.ncbi.nlm.nih.gov/pubmed/18070176", "http://www.ncbi.nlm.nih.gov/pubmed/24306957", "http://www.ncbi.nlm.nih.gov/pubmed/18923359", "http://www.ncbi.nlm.nih.gov/pubmed/24140246", "http://www.ncbi.nlm.nih.gov/pubmed/19181545", "http://www.ncbi.nlm.nih.gov/pubmed/22426337", "http://www.ncbi.nlm.nih.gov/pubmed/22615872", "http://www.ncbi.nlm.nih.gov/pubmed/22888342", "http://www.ncbi.nlm.nih.gov/pubmed/20960509", "http://www.ncbi.nlm.nih.gov/pubmed/23764080", "http://www.ncbi.nlm.nih.gov/pubmed/19565266", "http://www.ncbi.nlm.nih.gov/pubmed/20082749", "http://www.ncbi.nlm.nih.gov/pubmed/24212086", "http://www.ncbi.nlm.nih.gov/pubmed/23945108", "http://www.ncbi.nlm.nih.gov/pubmed/20657287", "http://www.ncbi.nlm.nih.gov/pubmed/24281040", "http://www.ncbi.nlm.nih.gov/pubmed/15341676", "http://www.ncbi.nlm.nih.gov/pubmed/23300915" ]

[ { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A7638941", "o": "C16181" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A7638941", "o": "Cancer Biomarkers Research Group" }, { "p": "http://www.w3.org/2008/05/skos-xl#prefLabel", "s": "http://linkedlifedata.com/resource/umls/id/C1516166", "o": "http://linkedlifedata.com/resource/umls/label/A7638941" }, { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A7638941", "o": "NCI Thesaurus" } ]

[ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001749", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D014554", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D014556", "http://www.disease-ontology.org/api/metadata/DOID:4007", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001743", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D055088", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D054316", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D042241", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D015415", "http://www.disease-ontology.org/api/metadata/DOID:6933", "http://www.uniprot.org/uniprot/BLCAP_HUMAN", "http://www.disease-ontology.org/api/metadata/DOID:11054" ]

[ "Short palindromic sequences (4, 5 and 6 bp palindromes) are avoided at a statistically significant level in the genomes of several bacteria, including the completely sequenced Haemophilus influenzae and Synechocystis sp. genomes and in the complete genome of the archaeon Methanococcus jannaschii. Palindromes corresponding to sites for restriction enzymes from other species are also avoided, albeit less significantly, suggesting that in the course of evolution bacterial DNA has been exposed to a wide spectrum of restriction enzymes, probably as the result of lateral transfer mediated by mobile genetic elements, such as plasmids and prophages. Palindromic words appear to accumulate in DNA once it becomes isolated from restriction-modification systems, as demonstrated by the case of organellar genomes." ]

[ "Short palindromic sequences (4, 5 and 6 bp palindromes)", "Palindromes corresponding to sites for restriction enzymes from other species" ]

[ "Avoidance of palindromic words in bacterial and archaeal genomes: a close connection with restriction enzymes.", "Short palindromic sequences (4, 5 and 6 bp palindromes) are avoided at a statistically significant level in the genomes of several bacteria, including the completely sequenced Haemophilus influenzae and Synechocystis sp. genomes and in the complete genome of the archaeon Methanococcus jannaschii.", "Palindromes corresponding to sites for restriction enzymes from other species are also avoided, albeit less significantly, suggesting that in the course of evolution bacterial DNA has been exposed to a wide spectrum of restriction enzymes, probably as the result of lateral transfer mediated by mobile genetic elements, such as plasmids and prophages", "Palindromic words appear to accumulate in DNA once it becomes isolated from restriction-modification systems, as demonstrated by the case of organellar genomes", "In certain cases, a comparison of avoided palindromic words in taxonomically related bacteria shows a pattern of relatedness of their R-M systems.", "Recognition sites for type II restriction and modification enzymes in genomes of several bacteria are recognized as semi-palindromic motifs and are avoided at a significant degree.", "On the basis of the set of most avoided words, and in accordance to the IUPAC coding standards, suggestions are made regarding potential recognition sequences. In certain cases, a comparison of avoided palindromic words in taxonomically related bacteria shows a pattern of relatedness of their R-M systems." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/12762852", "http://www.ncbi.nlm.nih.gov/pubmed/9171096" ]

[]

[]

[ "KRAS mutation has been unambiguously identified as a marker of resistance to cetuximab-based treatment in metastatic colorectal cancer (mCRC) patients.\nOther genes are such as EGFR, BRAF and T53 have also been suggested to be genotyped in order to evaluate the drug responsivness." ]

[ "KRAS", "EGFR", "BRAF", "T53" ]

[ "Treatment of metastatic colorectal cancer with targeted anti-EGFR therapeutics such as cetuximab extends survival in only 25% of patients who test wild-type for KRAS, while the majority of patients prove resistant (J Clin Oncol 28(7):1254-1261, 2010).", ". Somatic mutation of the EGFR signalling pathway is a prevalent mechanism of resistance to cetuximab (Nature 486(7404):532-536, 2012). If the human genome harbours variants that influence susceptibility of the EGFR pathway to oncogenic mutation, such variants could also be prognostic for cetuximab responsiveness. ", "KRAS mutations are strong predictors for clinical outcomes of EGFR-targeted treatments such as cetuximab and panitumumab in metastatic colorectal cancer (mCRC).", "KRAS mutation is widely accepted as a strong, negative predictive marker for anti-epidermal growth factor receptor antibodies, including cetuximab and panitumumab. ", "KRAS status is now a mandatory prerequisite in order to treat metastatic colorectal patients with anti-Epidermal Growth Factor Receptor (EGFR) antibodies, such as cetuximab or panitumumab. KRAS mutations are unambiguously linked to a lack of response to these targeted therapies.", "The EGFR-R497K polymorphism is a potential predictor for overall survival in HNSCC patients treated with cetuximab based therapy in the palliative setting.", "Laboratories are increasingly required to perform molecular tests for the detection of mutations in the KRAS gene in metastatic colorectal cancers to allow better clinical management and more effective treatment for these patients. KRAS mutation status predicts a patient's likely response to the monoclonal antibody cetuximab.", "KRAS mutation has been unambiguously identified as a marker of resistance to cetuximab-based treatment in metastatic colorectal cancer (mCRC) patients. ", " This study suggested EGF A+61G polymorphism to be a predictive marker for pCR, independent of KRAS mutation status, to cetuximab-based neoadjuvant chemoradiation of patients with locally advanced rectal cancer.", "Intratumoral gene expression levels of EGFR, VEGFR2 and NRP as well as polymorphisms in FCGR3A, CyclinD1 and EGFR could predict clinical outcome in mCRC patients enrolled in BOND2, independent of KRAS mutation status.", "Numerous clinical studies have shown that anti-EGFR therapies are effective only in a subset of patients with colorectal cancer. Even though mutations in the KRAS gene have been confirmed as negative predictors of the response to EGFR-targeted therapies, not all KRAS wild-type (wt-KRAS) patients will respond to treatment. Recent studies have demonstrated that additionally wild-type BRAF (wt-BRAF) genotype is required for response to panitumumab or cetuximab, suggesting that BRAF genotype criteria should be used together with KRAS genotype for selecting the patients who are about to benefit from the anti-EGFR therapy.", "KRAS mutation is a dramatic example of single nucleotide polymorphism, which is able to identify a priori patients that could receive or not an anti-EGFR monoclonal antibody such as cetuximab or panitumumab. ", "While confirming the negative effect of KRAS mutations on outcome after cetuximab, we show that BRAF, NRAS, and PIK3CA exon 20 mutations are significantly associated with a low response rate.", "Cetuximab and panitumumab, mAbs targeting EGFR, are registered for metastatic colorectal carcinoma (mCRC) patients whose tumors express EGFR as determined by immunohistochemistry. However, this method is not predictive of treatment efficacy.", ". This study suggests that TP53 mutations are predictive of cetuximab sensitivity, particularly in patients without KRAS mutation, and that TP53 genotyping could have a clinical interest to select patients who should benefit from cetuximab-based CT.", "A KRAS mutation confers resistance to cetuximab, which reduces treatment options, especially in first-line. ", "KRAS genotyping was recently introduced as predictive biomarker, since only tumors carrying a wildtype were found to respond to treatment with panitumumab." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/20645028", "http://www.ncbi.nlm.nih.gov/pubmed/21686179", "http://www.ncbi.nlm.nih.gov/pubmed/19367287", "http://www.ncbi.nlm.nih.gov/pubmed/24152305", "http://www.ncbi.nlm.nih.gov/pubmed/19368524", "http://www.ncbi.nlm.nih.gov/pubmed/21851273", "http://www.ncbi.nlm.nih.gov/pubmed/22287728", "http://www.ncbi.nlm.nih.gov/pubmed/21036743", "http://www.ncbi.nlm.nih.gov/pubmed/18810446", "http://www.ncbi.nlm.nih.gov/pubmed/20619739", "http://www.ncbi.nlm.nih.gov/pubmed/21673069", "http://www.ncbi.nlm.nih.gov/pubmed/20637356", "http://www.ncbi.nlm.nih.gov/pubmed/19343364", "http://www.ncbi.nlm.nih.gov/pubmed/23671647", "http://www.ncbi.nlm.nih.gov/pubmed/23299277", "http://www.ncbi.nlm.nih.gov/pubmed/22735045" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005838", "http://www.biosemantics.org/jochem#4002122" ]

[ "(STAT3) is a latent cytoplasmic transcription factor, originally discovered as a transducer of signal from cell surface receptors to the nucleus. It is activated by tyrosine phosphorylation at position 705 leading to its dimerization, nuclear translocation, DNA binding, and activation of gene transcription. Under normal physiological conditions, STAT3 activation is tightly regulated. However, compelling evidence suggests that STAT3 is constitutively activated in many cancers and plays a pivotal role in tumor growth and metastasis. It regulates cellular proliferation, invasion, migration, and angiogenesis that are critical for cancer metastasis" ]

[ "yes" ]

[ " (STAT3) is critical for cancer progression by regulating tumor cell survival, proliferation, and angiogenesis. Herein, we investigated the regulation of STAT3 activation and the therapeutic effects of Icaritin, a prenyl flavonoid derivative from Epimedium Genus, in renal cell carcinoma (RCC). ", " Overall, these results suggest that Icaritin strongly inhibits STAT3 activation and is a potentially effective therapeutic option for the treatment of renal cell carcinoma", "we have reviewed important signaling pathways that are closely related to radiosensitization, such as cell cycle arrest, tumor angiogenesis, JAK/STAT3 signaling pathway and Mismatch repair", "Interleukin-27 signaling is mediated by the JAK-STAT pathway via activation of STAT1 and STAT3, which have tumor suppressive and oncogenic activities, respectively. Epithelial-mesenchymal transition (EMT) and angiogenesis are key processes in carcinogenesis.", "The inhibition of STAT3 activation had no effect on the development of the epithelial phenotype.", "STAT3 plays a vital role in inducing and maintaining a pro-carcinogenic inflammatory microenvironment and is reported to be a critical mediator of the oncogenic effects of EGFR mutations. STAT3 activation is mediated through JAK family kinases", " EESB treatment could significantly suppress the activation of several CRC-related pathways, including STAT3, Erk, and p38 signalings in tumor tissues, and alter the expression of multiple critical target genes such as Bcl-2, Bax, Cyclin D1, CDK4, and p21. These molecular effects lead to the induction of cancer cell apoptosis and inhibition of cell proliferation. Our findings demonstrate that SB possesses a broad range of antitumor activities because of its ability to affect multiple intracellular targets", "Western immunoblotting analyses of mouse lung tissues indicated significantly lower level of pSTAT3 and Mcl-1 in the carcinogen plus DMAPT group relative to the group treated with the carcinogen only. Given the evidence that STAT3 is activated in more than half of lung cancers and it regulates genes involved in cell proliferation, survival and angiogenesis, DMAPT is a promising agent for lung cancer chemoprevention in subjects who are at high risk of developing this devastating disease.", "(STAT3) is a latent cytoplasmic transcription factor, originally discovered as a transducer of signal from cell surface receptors to the nucleus. It is activated by tyrosine phosphorylation at position 705 leading to its dimerization, nuclear translocation, DNA binding, and activation of gene transcription. Under normal physiological conditions, STAT3 activation is tightly regulated. However, compelling evidence suggests that STAT3 is constitutively activated in many cancers and plays a pivotal role in tumor growth and metastasis. It regulates cellular proliferation, invasion, migration, and angiogenesis that are critical for cancer metastasis", "STAT3) signaling pathway plays important roles in oncogenesis, angiogenesis, immunity, and tumor cell invasion. In the present study, we investigated the association of interleukin ", " Phosphorylated STAT3 (pSTAT3) regulates many genes that are necessarily expressed in cancer initiation, development, and progression, being involved in proliferation, anti-apoptosis, invasion, angiogenesis, and immune surveillance evasion" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/24042330", "http://www.ncbi.nlm.nih.gov/pubmed/20204067", "http://www.ncbi.nlm.nih.gov/pubmed/24305878", "http://www.ncbi.nlm.nih.gov/pubmed/24058783", "http://www.ncbi.nlm.nih.gov/pubmed/24200081", "http://www.ncbi.nlm.nih.gov/pubmed/22076197", "http://www.ncbi.nlm.nih.gov/pubmed/24307888", "http://www.ncbi.nlm.nih.gov/pubmed/17610223", "http://www.ncbi.nlm.nih.gov/pubmed/23848338", "http://www.ncbi.nlm.nih.gov/pubmed/24238495", "http://www.ncbi.nlm.nih.gov/pubmed/23962559", "http://www.ncbi.nlm.nih.gov/pubmed/23848964", "http://www.ncbi.nlm.nih.gov/pubmed/20052595", "http://www.ncbi.nlm.nih.gov/pubmed/18498667", "http://www.ncbi.nlm.nih.gov/pubmed/15665295", "http://www.ncbi.nlm.nih.gov/pubmed/24324713", "http://www.ncbi.nlm.nih.gov/pubmed/24178245", "http://www.ncbi.nlm.nih.gov/pubmed/24005169", "http://www.ncbi.nlm.nih.gov/pubmed/16061629", "http://www.ncbi.nlm.nih.gov/pubmed/23903834", "http://www.ncbi.nlm.nih.gov/pubmed/24274066", "http://www.ncbi.nlm.nih.gov/pubmed/24199193", "http://www.ncbi.nlm.nih.gov/pubmed/19566485", "http://www.ncbi.nlm.nih.gov/pubmed/24231788", "http://www.ncbi.nlm.nih.gov/pubmed/9091577", "http://www.ncbi.nlm.nih.gov/pubmed/24116074" ]

[ { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A10788344", "o": "C39238" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C1514955", "o": "http://linkedlifedata.com/resource/umls/label/A10788344" }, { "p": "http://linkedlifedata.com/resource/umls/altMetaMap", "s": "http://linkedlifedata.com/resource/umls/id/C1514955", "o": "http://linkedlifedata.com/resource/umls/label/A10788344" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A10788344", "o": "Stat3 Signaling Pathway" }, { "p": "http://linkedlifedata.com/resource/umls/prefMetaMap", "s": "http://linkedlifedata.com/resource/umls/id/C1514955", "o": "http://linkedlifedata.com/resource/umls/label/A7663266" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A7663266", "o": "C39238" }, { "p": "http://purl.uniprot.org/core/citation", "s": "http://purl.uniprot.org/uniprot/Q7Z4H9", "o": "http://purl.uniprot.org/citations/12853948" }, { "p": "http://purl.uniprot.org/core/name", "s": "http://purl.uniprot.org/pubmed/12853948", "o": "Nature" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_51375A34483900F", "o": "STAT3-interacting protein as a repressor" }, { "p": "http://www.w3.org/2004/02/skos/core#exactMatch", "s": "http://purl.uniprot.org/pubmed/12853948", "o": "http://purl.uniprot.org/pubmed/12853948" }, { "p": "http://www.w3.org/2004/02/skos/core#exactMatch", "s": "http://purl.uniprot.org/pubmed/12853948", "o": "http://purl.uniprot.org/medline/22737999" }, { "p": "http://purl.uniprot.org/core/recommendedName", "s": "http://purl.uniprot.org/uniprot/Q7Z4H9", "o": "http://linkedlifedata.com/resource/#_51375A34483900F" }, { "p": "http://linkedlifedata.com/resource/relationontology/expressedInCellLine", "s": "http://purl.uniprot.org/uniprot/Q3ZN08", "o": "http://purl.uniprot.org/tissues/597" }, { "p": "http://purl.uniprot.org/core/alternativeName", "s": "http://purl.uniprot.org/uniprot/Q3ZN08", "o": "http://linkedlifedata.com/resource/#_51335A4E30380015" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://purl.uniprot.org/tissues/597", "o": "Breast tumor" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://purl.uniprot.org/tissues/597", "o": "Mammary tumour" }, { "p": "http://purl.uniprot.org/core/recommendedName", "s": "http://purl.uniprot.org/uniprot/Q3ZN08", "o": "http://linkedlifedata.com/resource/#_51335A4E30380014" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_51335A4E30380014", "o": "STAT3-interacting protein as a repressor" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_51335A4E30380015", "o": "Acrosomal protein ACPIN1" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://purl.uniprot.org/tissues/597", "o": "Mammary tumor" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://purl.uniprot.org/tissues/597", "o": "Mammary gland tumor" } ]

[ "http://www.uniprot.org/uniprot/STAT3_MOUSE", "http://www.biosemantics.org/jochem#4243664", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0045766", "http://www.uniprot.org/uniprot/STAT3_CHICK", "http://www.uniprot.org/uniprot/STAT3_HUMAN", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0045765", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D043925", "http://www.uniprot.org/uniprot/STAT3_BOVIN", "http://www.uniprot.org/uniprot/STAT3_RAT", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D050796", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0001525", "http://www.uniprot.org/uniprot/STAT3_PIG", "http://www.uniprot.org/uniprot/STATC_DICDI", "http://www.disease-ontology.org/api/metadata/DOID:162" ]

[ "QUALITY CONTROL", "The physiological target for LeuRS translational quality control is norvaline.", "The fidelity of protein synthesis depends on the capacity of aminoacyl-tRNA synthetases (AARSs) to couple only cognate amino acid-tRNA pairs. If amino acid selectivity is compromised, fidelity can be ensured by an inherent AARS editing activity that hydrolyses mischarged tRNAs. Rather, as shown by kinetic, structural and in vivo approaches, the prime biological function of LeuRS editing is to prevent mis-incorporation of the non-standard amino acid norvaline." ]

[ "Norvaline" ]

[ "The physiological target for LeuRS translational quality control is norvaline.", "The physiological target for LeuRS translational quality control is norvaline", "Rather, as shown by kinetic, structural and in vivo approaches, the prime biological function of LeuRS editing is to prevent mis-incorporation of the non-standard amino acid norvaline" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/24935946" ]

[]

[ "http://www.uniprot.org/uniprot/SYL_SHEWM", "http://www.uniprot.org/uniprot/SYL_SHESR", "http://www.uniprot.org/uniprot/SYL_COXBR", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D007935", "http://www.uniprot.org/uniprot/SYL_SHESW", "http://www.uniprot.org/uniprot/SYLC_MOUSE", "http://www.uniprot.org/uniprot/SYL_SHIB3", "http://www.uniprot.org/uniprot/SYLC_ENCCU", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011786", "http://www.uniprot.org/uniprot/SYL_SHESA", "http://www.uniprot.org/uniprot/SYL_RICPU", "http://www.uniprot.org/uniprot/SYLB_AQUAE", "http://www.uniprot.org/uniprot/SYLC_SCHPO", "http://www.uniprot.org/uniprot/SYL_SHIBS", "http://www.uniprot.org/uniprot/SYL2_METS5" ]

[ "Yes, sumoylation is implicated in myogenesis.", "Yes, protein sumoylation present in myoblasts is regulated in myogenesis." ]

[ "yes" ]

[ "Sentrin/small ubiquitin-like modifier (SUMO)-specific protease 2 (SENP2) has broad de-SUMOylation activities in vitro, which is essential for embryonic heart development.", "Silencing SENP2 can reduce myostatin expression and, therefore, promote myogenesis of skeletal muscle. These results reveal the important role of SENP2 in the regulation of myostatin expression and myogenesis.", "Overexpression of c-Ski/SnoN also induces skeletal muscle differentiation, but how c-Ski/SnoN function in myogenesis is largely unknown.", "Notably, loss of sumoylation in the Lys-50 site (via a Lys-to-Arg point mutation) potently activates muscle-specific gene expression and enhances myotube formation. Our study suggests a novel role for SUMO modification in the regulation of myogenic differentiation.", "Although this modification has little effect on SnoN repression of the plasminogen activator inhibitor-1 promoter and only modestly potentiates SnoN repression of the p21 promoter, SnoN sumoylation robustly augments the ability of SnoN to suppress transcription of the myogenesis master regulatory gene myogenin", "Our study also points to a physiological role for SnoN sumoylation in the control of myogenin expression in differentiating muscle cells.", "Here, we biochemically characterize SnoN sumoylation in detail and report the physiological function of the modification. ", "An essential role of small ubiquitin-like modifier (SUMO)-specific Protease 2 in myostatin expression and myogenesis.", "These results reveal the important role of SENP2 in the regulation of myostatin expression and myogenesis.", "The E3 SUMO ligase Nse2 regulates sumoylation and nuclear-to-cytoplasmic translocation of skNAC-Smyd1 in myogenesis.", "Sumoylation of the basic helix-loop-helix transcription factor sharp-1 regulates recruitment of the histone methyltransferase G9a and function in myogenesis.", " We show that the overall load of sumoylated proteins present in myoblasts diminishes progressively throughout myogenesis", "These novel results suggest that protein sumoylation plays a pivotal role in myoblast differentiation and is required to regulate the activity of key targets downstream of MyoD and myogenin.", "a composite sequence motif has recently been identified that couples phosphorylation, sumoylation, and perhaps also deacetylation to control transcriptional repression in stress response, mitogen and nuclear hormone signaling, myogenesis, and neuronal differentiation.", "Mutation of these SUMO acceptor sites in Sharp-1 does not impact its subcellular localization but attenuates its ability to act as a transcriptional repressor and inhibit myogenic differentiation. Consistently, co-expression of the SUMO protease SENP1 with wild type Sharp-1 abrogates Sharp-1-dependent inhibition of myogenesis. ", "Transforming growth factor-beta-independent regulation of myogenesis by SnoN sumoylation.", "Ubiquitin Specific Protease 25 (USP25), a member of the deubiquitinase family, is involved in several disease-related signal pathways including myogenesis, immunity and protein degradation. ", " In addition, we show that the skNAC interaction partner Smyd1 contains a putative sumoylation motif and is sumoylated in muscle cells, with depletion of Mms21/Nse2 leading to reduced concentrations of sumoylated Smyd1. Taken together, our data suggest that the function, specifically the balance between the nuclear and cytosolic roles, of the skNAC-Smyd1 complex might be regulated by sumoylation." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/16973431", "http://www.ncbi.nlm.nih.gov/pubmed/24344126", "http://www.ncbi.nlm.nih.gov/pubmed/23247248", "http://www.ncbi.nlm.nih.gov/pubmed/25002400", "http://www.ncbi.nlm.nih.gov/pubmed/16631162", "http://www.ncbi.nlm.nih.gov/pubmed/17202138", "http://www.ncbi.nlm.nih.gov/pubmed/16478538", "http://www.ncbi.nlm.nih.gov/pubmed/23637228", "http://www.ncbi.nlm.nih.gov/pubmed/16966324", "http://www.ncbi.nlm.nih.gov/pubmed/23754700" ]

[ { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A18469770", "o": "D058207" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A7814146", "o": "D024510" } ]

[ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D024510", "http://amigo.geneontology.org/amigo/term/GO:0016925", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D058207" ]

[ "Randomised studies have demonstrated the efficacy of hypothermia for the treatment of perinatal hypoxic-ischaemic encephalopathy (HIE) in reducing rate of death or neurodevelopmental disabilities in term or late preterm infants. It remains unclear to what degree preterm infants were included in these studies.\nA prospective non-randomised pilot study reported that mild hypothermia for 48 hours in preterm neonates with severe NEC (necrotising enterocolitis) seems both feasible and safe." ]

[]

[ "Therapeutic hypothermia is a recognized treatment for term infants with hypoxic-ischemic encephalopathy (HIE) in reducing rate of death or neurodevelopmental disabilities. Little is known about applications of this treatment to preterm newborns.", "Randomised studies have demonstrated the efficacy of hypothermia for the treatment of perinatal hypoxic-ischaemic encephalopathy (HIE) in term or late preterm infants.", "We aimed to establish the feasibility and safety of mild hypothermia in preterm neonates with NEC and MODS as a prelude to a randomized trial. METHODS: This was a prospective, nonrandomized pilot study of 15 preterm infants who were referred for surgical intervention of advanced NEC and failure of at least 3 organs. Whole-body cooling was achieved by ambient temperature adjustment with or without cooling mattress", "Mild hypothermia for 48 hours in preterm neonates with severe NEC seems both feasible and safe. Additional investigation of the efficacy of this therapeutic intervention in this population is warranted." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/20470651", "http://www.ncbi.nlm.nih.gov/pubmed/20100756", "http://www.ncbi.nlm.nih.gov/pubmed/22320395", "http://www.ncbi.nlm.nih.gov/pubmed/19020525" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D007036", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D047928", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D007234", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D007235", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D007752" ]

[ "Stain-Free technology can be used as a normalization tool in Western blot analysis." ]

[]

[ "V3 stain-free workflow for a practical, convenient, and reliable total protein loading control in western blotting.", "The V3 stain-free workflow makes the western blot process faster, transparent, more quantitative and reliable.", "Direct Blue 71 (DB71) staining-a novel, sensitive, dye-binding staining method compatible with immunodetection-may offer advantages over these traditional loading control methods.", "Direct Blue 71 staining as a destaining-free alternative loading control method for Western blotting.", "Stain-Free technology as a normalization tool in Western blot analysis.", "Stain-Free technology appears to be more reliable, more robust, and more sensitive", "tain-Free technology offers the additional advantages of providing checkpoints throughout the Western blotting process by allowing rapid visualization of gel separation and protein transfer." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/23085117", "http://www.ncbi.nlm.nih.gov/pubmed/23712695", "http://www.ncbi.nlm.nih.gov/pubmed/24429481" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D015153", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013194", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005782" ]

[ "Denosumab (Dmab) is a fully human monoclonal antibody against the receptor activator of nuclear factor-κB ligand (RANKL)." ]

[ "receptor activator of nuclear factor-κB ligand", "RANKL" ]

[ "Denosumab is a human monoclonal antibody which specifically blocks receptor activator of nuclear factor κB ligand and is a very potent antiresorptive drug. ", "denosumab, a monoclonal antibody against RANKL", "Denosumab is a human monoclonal antibody indicated for the treatment of osteoporosis in postmenopausal women with a high risk of fractures. ", "Denosumab (Dmab) is a fully human monoclonal antibody against the receptor activator of nuclear factor-κB ligand (RANKL), which, through the prevention of the RANKL/RANK interaction, inhibits osteoclast-mediated bone resorption and significantly reduces the risk of vertebral, nonvertebral, and hip fractures. " ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/26504466", "http://www.ncbi.nlm.nih.gov/pubmed/26029270", "http://www.ncbi.nlm.nih.gov/pubmed/26508890", "http://www.ncbi.nlm.nih.gov/pubmed/26203221" ]

[]

[]

[ "Fostamatinib (R788) acts by inhibiting spleen tyrosine kinase. Fostamatinib (R788) is a prodrug rapidly converted to its active metabolite on oral administration. This (known as R406) is a potent inhibitor of spleen tyrosine kinase that is required for the expression of a number of proinflammatory cytokines. Fostamatinib has been shown to be effective in patients with rheumatoid arthritis, leukemia, lymphoma, bronchial asthma and thrombocytopenic purpura." ]

[ "spleen tyrosine kinase" ]

[ "It outlines preclinical and early clinical experiences with the Syk inhibitor fostamatinib disodium (R788) and discusses various options for further clinical development of this compound. ", "To assess the efficacy and safety of R788 (fostamatinib disodium), an inhibitor of spleen tyrosine kinase (Syk), in patients with active rheumatoid arthritis (RA) that did not respond to biologic therapies. ", "The mTOR inhibitors temsirolimus and everolimus have demonstrated antitumor activity in all types of lymphoma, the Syk inhibitor fostamatinib has activity in diffuse large B-cell lymphoma and chronic lymphocytic leukemia, and the PKC-β inhibitor enzastaurin is being used as consolidation therapy after remission in diffuse large B-cell lymphoma. ", "Fostamatinib, a Syk-kinase inhibitor, does not affect methotrexate pharmacokinetics in patients with rheumatoid arthritis.", "The objective of this phase 2 study was to evaluate the efficacy and safety of R788, an oral inhibitor of Syk, in patients with active rheumatoid arthritis despite methotrexate therapy.", "The Syk inhibitor fostamatinib disodium (R788) inhibits tumor growth in the Eμ- TCL1 transgenic mouse model of CLL by blocking antigen-dependent B-cell receptor signaling.", "We have now investigated whether inhibition of BCR signaling with the selective Syk inhibitor fostamatinib disodium (R788) will affect the growth of the leukemias that develop in the Eμ-TCL1 transgenic mouse model of CLL.", "We show that conditional ablation of the syk gene in dendritic cells (DCs) abrogates FcgammaR-mediated cross priming of diabetogenic T cells in RIP-mOVA mice, a situation phenocopied in wild-type RIP-mOVA mice treated with the selective Syk inhibitor R788.", "We investigated the ability of a small drug Syk inhibitor, R788, to protect mice against mesenteric ischemia-reperfusion (I/R)-induced local (intestine) and remote lung injury.", "The spleen tyrosine kinase (Syk) inhibitor R406 is orally administered as the prodrug R788. ", "Inhibition of Syk with fostamatinib disodium has significant clinical activity in non-Hodgkin lymphoma and chronic lymphocytic leukemia.", "These data prompted a phase 1/2 clinical trial of fostamatinib disodium, the first clinically available oral Syk inhibitor, in patients with recurrent B-cell non-Hodgkin lymphoma (B-NHL). ", "We examined the effect of R788 (fostamatinib disodium), an oral prodrug of the selective Syk inhibitor R406, in nephrotoxic nephritis in Wistar-Kyoto rats.", "Fostamatinib, a Syk inhibitor prodrug for the treatment of inflammatory diseases.", "Rigel Pharmaceuticals Inc is developing fostamatinib, a prodrug of the spleen tyrosine kinase (Syk) inhibitor R-406, for the potential treatment of autoimmune diseases such as rheumatoid arthritis (RA), idiopathic thrombocytopenic purpura (ITP) and B-cell lymphomas.", "In developmental toxicity studies with the Syk kinase inhibitor R788, a spectrum of findings, including renal agenesis, were observed.", "R788, a prodrug of active metabolite R406, has been shown to be an inhibitor of Syk kinase, active in a variety of in vitro and in vivo models, suggesting potential activity in the treatment of rheumatoid arthritis (RA). ", "In collagen-induced arthritis, R788/R406, a novel and potent small molecule Syk inhibitor suppressed clinical arthritis, bone erosions, pannus formation, and synovitis. ", "Fostamatinib (R788) inhibits spleen tyrosine kinase (Syk) and has been in clinical trials involving both MTX inadequate responders (MTX-IRs) and biologic inadequate responders. ", "The compounds that are currently investigated in patients with CLL include ibrutinib -inhibitor of Btk, fostamatinib-inhibitor of Syk and idelalisib (GS-1101) -a specific isoform of the PI3K (PI3K) inhibitor. ", "TK inhibitors including spleen TK (fostamatinib) and Janus kinases (tofacitinib) inhibitors are two novel oral therapies that have demonstrated short-term good clinical responses in active rheumatoid arthritis patients with and inadequate responses to methotrexate or other traditional (non-biologic) disease-modifying antirheumatic drugs (DMARDs). ", "Progress is also being made with orally active Syk inhibitors. One such inhibitor (fostamatinib) is currently in large-scale phase 3 trials, and there are others in clinical development.", "We have shown that R406, the active metabolite of the Syk inhibitor fostamatinib, induces apoptosis and cell cycle arrest while decreasing downstream phosphatidylinositol-3'-kinase (PI3K)/Akt signaling in EBV+ B cell lymphoma PTLD lines in vitro.", "Effects of fostamatinib (R788), an oral spleen tyrosine kinase inhibitor, on health-related quality of life in patients with active rheumatoid arthritis: analyses of patient-reported outcomes from a randomized, double-blind, placebo-controlled trial.", "Pharmacokinetics of fostamatinib, a spleen tyrosine kinase (SYK) inhibitor, in healthy human subjects following single and multiple oral dosing in three phase I studies.", "Fostamatinib (R788) is an orally dosed prodrug designed to deliver the active metabolite R940406 (R406), a spleen tyrosine kinase (SYK) inhibitor, for the treatment of rheumatoid arthritis.", "Fostamatinib demonstrates rapid and extensive conversion to R406, an inhibitor of SYK.", "Fostamatinib, a Syk inhibitor that successfully completed phase II clinical trials, also exhibits some undesirable side effects.", "Fostamatinib (R788) is a prodrug rapidly converted to its active metabolite on oral administration. This (known as R406) is a potent inhibitor of spleen tyrosine kinase, required for the expression of a number of proinflammatory cytokines. ", "The Syk inhibitor, fostamatinib, proved superior to placebo in Phase II trials and is currently under Phase III investigation. T", "More recently, several KIs have been developed to target the proximal B-cell receptor (BCR) signaling pathway including spleen tyrosine kinase inhibitor (Fostamatinib) and Bruton's tyrosine kinase inhibitors (Ibrutinib, AVL-263). ", "Because inhibitors of SYK activity, such as fostamatinib, are in advanced clinical trials for rheumatoid arthritis and other autoimmune diseases, understanding the role of SYK in signalling via TLR4 is of immediate importance. ", "The search terms used were Bruton's tyrosine kinase (Btk) inhibitors, PCI-32765, GDC-0834, LFM-A13, AVL-101, AVL-292, spleen tyrosine kinase (Syk) inhibitors, R343, R406, R112, R788, fostamatinib, BAY-61-3606, C-61, piceatannol, Lyn, imatinib, nilotinib, bafetinib, dasatinib, GDC-0834, PP2, SU6656 in conjunction with lymphoid malignancy, NHL, CLL, autoimmune disease, allergic disease, asthma, and rheumatoid arthritis.", "Inhibition of Syk activity by R788 in platelets prevents remote lung tissue damage after mesenteric ischemia-reperfusion injury.", "Recently, Syk inhibitor fostamatinib has exerted potent therapeutic efficacy against autoimmune and allergic diseases such as rheumatoid arthritis (RA), bronchial asthma and thrombocytopenic purpura (ITP).", "In chronic lymphocytic leukemia (CLL), Syk becomes activated by external signals from the tissue microenvironment, and was targeted in a first clinical trial with R788 (fostamatinib), a relatively nonspecific Syk inhibitor.", "In vivo expansion of luciferase(+) donor Tcs in mice developing GvHD was reduced by treatment with the Syk inhibitor Fostamatinib, which led to increased survival and reduced histologically confirmed GvHD severity.", "Syk inhibition with fostamatinib leads to transitional B lymphocyte depletion.", "No oral biologic agents are available at this time but promising data is emerging for two drugs, tofacitinib and fostamatinib, inhibitors of JAK and Syk kinases, respectively. ", "Fostamatinib (R-788) is an orally bioavailable small molecule. It is the prodrug of R406, which is a potent Syk inhibitor. ", "The oral spleen tyrosine kinase inhibitor fostamatinib attenuates inflammation and atherogenesis in low-density lipoprotein receptor-deficient mice.", "Low-density lipoprotein receptor-deficient mice consuming a high-cholesterol diet supplemented with 2 doses of the orally available SYK inhibitor fostamatinib for 16 weeks showed a dose-dependent reduction in atherosclerotic lesion size by up to 59±6% compared with the respective controls. " ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/20716772", "http://www.ncbi.nlm.nih.gov/pubmed/23233565", "http://www.ncbi.nlm.nih.gov/pubmed/21304505", "http://www.ncbi.nlm.nih.gov/pubmed/20879879", "http://www.ncbi.nlm.nih.gov/pubmed/22374444", "http://www.ncbi.nlm.nih.gov/pubmed/21239804", "http://www.ncbi.nlm.nih.gov/pubmed/23151054", "http://www.ncbi.nlm.nih.gov/pubmed/23378467", "http://www.ncbi.nlm.nih.gov/pubmed/23190017", "http://www.ncbi.nlm.nih.gov/pubmed/21394647", "http://www.ncbi.nlm.nih.gov/pubmed/17537677", "http://www.ncbi.nlm.nih.gov/pubmed/23055694", "http://www.ncbi.nlm.nih.gov/pubmed/22421457", "http://www.ncbi.nlm.nih.gov/pubmed/23574525", "http://www.ncbi.nlm.nih.gov/pubmed/21438742", "http://www.ncbi.nlm.nih.gov/pubmed/21209239", "http://www.ncbi.nlm.nih.gov/pubmed/22492694", "http://www.ncbi.nlm.nih.gov/pubmed/20601600", "http://www.ncbi.nlm.nih.gov/pubmed/23094030", "http://www.ncbi.nlm.nih.gov/pubmed/22301676", "http://www.ncbi.nlm.nih.gov/pubmed/23078058", "http://www.ncbi.nlm.nih.gov/pubmed/20522642", "http://www.ncbi.nlm.nih.gov/pubmed/19333898", "http://www.ncbi.nlm.nih.gov/pubmed/21700926", "http://www.ncbi.nlm.nih.gov/pubmed/21279990", "http://www.ncbi.nlm.nih.gov/pubmed/22035435", "http://www.ncbi.nlm.nih.gov/pubmed/19965662", "http://www.ncbi.nlm.nih.gov/pubmed/22357358", "http://www.ncbi.nlm.nih.gov/pubmed/23861534", "http://www.ncbi.nlm.nih.gov/pubmed/22166799", "http://www.ncbi.nlm.nih.gov/pubmed/22362000", "http://www.ncbi.nlm.nih.gov/pubmed/24072968", "http://www.ncbi.nlm.nih.gov/pubmed/18975322", "http://www.ncbi.nlm.nih.gov/pubmed/22875912", "http://www.ncbi.nlm.nih.gov/pubmed/23281837", "http://www.ncbi.nlm.nih.gov/pubmed/23523202", "http://www.ncbi.nlm.nih.gov/pubmed/23617253", "http://www.ncbi.nlm.nih.gov/pubmed/20415544", "http://www.ncbi.nlm.nih.gov/pubmed/24455520", "http://www.ncbi.nlm.nih.gov/pubmed/19959716", "http://www.ncbi.nlm.nih.gov/pubmed/22284392", "http://www.ncbi.nlm.nih.gov/pubmed/22830347", "http://www.ncbi.nlm.nih.gov/pubmed/21711059", "http://www.ncbi.nlm.nih.gov/pubmed/19107952", "http://www.ncbi.nlm.nih.gov/pubmed/24376763", "http://www.ncbi.nlm.nih.gov/pubmed/22776094", "http://www.ncbi.nlm.nih.gov/pubmed/21211067", "http://www.ncbi.nlm.nih.gov/pubmed/23717217", "http://www.ncbi.nlm.nih.gov/pubmed/23398911", "http://www.ncbi.nlm.nih.gov/pubmed/23170196", "http://www.ncbi.nlm.nih.gov/pubmed/23642011", "http://www.ncbi.nlm.nih.gov/pubmed/22612424", "http://www.ncbi.nlm.nih.gov/pubmed/23455231", "http://www.ncbi.nlm.nih.gov/pubmed/21878134", "http://www.ncbi.nlm.nih.gov/pubmed/23431463", "http://www.ncbi.nlm.nih.gov/pubmed/23133664" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004798", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004791", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004364" ]

[ "Miller Fisher syndrome is a variant of Guillain-Barre syndrome characterized by the classic triad of ophthalmoplegia, ataxia, and areflexia", "Miller-Fisher syndrome is a variant of Guillain-Barré syndrome, characterized by the classic triad of ophthalmoplegia, ataxia, and areflexia." ]

[ "yes" ]

[ "Miller Fisher syndrome is a variant of Guillain-Barre syndrome characterized by the classic triad of ophthalmoplegia, ataxia, and areflexia", "We are reporting a rare case of Miller-Fisher (MFS) variant of Guillain-Barré syndrome (GBS) as the first manifestation of SLE in a 41-year-old female", "Miller-Fisher syndrome is defined as ophthalmoplegia, ataxia and areflexia. Considered as a variant of Guillain-Barré syndrome, it differs in its clinical presentation and by anti-GQ1b antibody positivity", "Guillain-Barré syndrome (GBS) and its variant, Miller Fisher syndrome (MFS), exist as several clinical subtypes with different neurological features and presentations", "Using in vitro and in vivo models of the Guillain-Barré syndrome variant, Miller Fisher syndrome, we have shown previously that anti-GQ1b ganglioside antibodies target the presynaptic motor nerve terminal axon and surrounding perisynaptic Schwann cells, thereby mediating destructive injury through deposition of membrane attack complex.", "Miller Fisher syndrome is a variant of Guillain-Barré syndrome, characterized by ophthalmoplegia, ataxia and areflexia.", "Miller Fisher syndrome is a localized variant of Guillain-Barré syndrome, characterized by ophthalmoplegia, areflexia and ataxia.", "Miller Fisher syndrome, a variant of Guillain-Barré syndrome, is associated with IgG antibody to GQ1b ganglioside.", "Miller Fisher syndrome (MFS), a variant of Guillain-Barré syndrome, is a rare disorder typically characterized by a triad of ataxia, areflexia, and ophthalmoplegia, which may have a highly variable clinical presentation.", "Miller Fisher syndrome is an acute inflammatory polyradiculoneuropathy that is generally considered a variant of Guillain-Barré syndrome and is characterized by the clinical triad of ataxia, areflexia, and ophthalmoplegia.", "The objective of this study was to review the occurrence and clinical features of Guillain-Barré syndrome and its variant, the Miller Fisher syndrome, during TNFalpha antagonist therapy.", "Miller Fisher variant of Guillain-Barré syndrome masquerading as acute sphenoid sinusitis with orbital apex syndrome.", "Controversy exists concerning whether Miller Fisher syndrome (MFS) is the result of a predominantly axonal or demyelinating polyneuropathy and whether the Guillain-Barré syndrome variant of acute ataxia and areflexia without ophthalmoplegia, ataxic Guillain-Barré syndrome (atxGBS), has a distinct pathophysiology.", "Miller Fisher syndrome is characterised by the triad ophthalmoparesis, ataxia and areflexia and is considered to be a variant of Guillain-Barré syndrome; its differential diagnosis includes Wernicke&apos;s encephalopathy", "Miller Fisher syndrome is an acute inflammatory polyradiculoneuropathy that is generally considered a variant of Guillain-Barré syndrome and is characterized by the clinical triad of ataxia, areflexia, and ophthalmoplegia", "Miller-Fisher syndrome is characterised by the clinical triad of ophthalmoplegia, ataxia and areflexia and is considered a variant form of Guillain-Barré syndrome", "The syndrome of ataxia, areflexia and ophthalmoplegia, or Miller-Fisher syndrome, has been considered to be a variant of Guillain-Barré syndrome with pathology restricted to the peripheral nervous system", "Miller-Fisher syndrome (MFS) is considered the most common variant of Guillain-Barré syndrome (GBS) and is characterized by the clinical triad of ophthalmoplegia, ataxia and areflexia", "Miller Fisher syndrome (MFS), characterized as ataxia, areflexia and ophthalmoplegia, is generally considered as a variant of Guillain-Barré syndrome (GBS)", "Miller Fisher Syndrome (MFS), which is characterized by ophthalmoplegia, ataxia and tendon areflexia, is generally considered as a clinical variant of Guillain-Barré Syndrome", "Miller-Fisher syndrome (MFS), a variant of Guillain-Barré syndrome (GBS) is a self-limiting demyelinating disease of the peripheral nervous system", "BACKGROUND: Miller-Fisher syndrome is characterised by the clinical triad of ophthalmoplegia, ataxia and areflexia and is considered a variant form of Guillain-Barré syndrome. ", "BACKGROUND AND OBJECTIVE: Miller-Fisher syndrome (MFS) is considered the most common variant of Guillain-Barré syndrome (GBS) and is characterized by the clinical triad of ophthalmoplegia, ataxia and areflexia. ", "Miller Fisher syndrome is characterised by the triad ophthalmoparesis, ataxia and areflexia and is considered to be a variant of Guillain-Barré syndrome; its differential diagnosis includes Wernicke's encephalopathy. ", "A recent report described serum anti-GQ1b ganglioside antibodies in Miller Fisher syndrome (MFS), a clinical variant of Guillain-Barré syndrome (GBS).", "The syndrome of ataxia, areflexia and ophthalmoplegia, or Miller-Fisher syndrome, has been considered to be a variant of Guillain-Barré syndrome with pathology restricted to the peripheral nervous system.", "Guillain-Barré syndrome (GBS), an acute inflammatory polyneuropathy, is preceded in most cases by an infectious illness, and Campylobacter jejuni, a leading cause of acute gastroenteritis, is the most common antecedent to GBS and its ocular variant, Miller Fisher syndrome (MFS).", "Miller-Fisher syndrome is characterised by the clinical triad of ophthalmoplegia, ataxia and areflexia and is considered a variant form of Guillain-Barré syndrome.", "Miller-Fisher syndrome is characterised by the clinical triad of ophthalmoplegia, ataxia and areflexia and is considered a variant form of Guillain-Barré syndrome.", " The syndrome of ataxia, areflexia and ophthalmoplegia, or Miller-Fisher syndrome, has been considered to be a variant of Guillain-Barré syndrome with pathology restricted to the peripheral nervous system. A patient with Miller-Fisher syndrome and bilateral demyelinating optic neuropathy suggesting associated central nervous system pathology is presented.", "Miller Fisher syndrome is an acute inflammatory polyradiculoneuropathy that is generally considered a variant of Guillain-Barré syndrome and is characterized by the clinical triad of ataxia,", " Miller Fisher syndrome is an uncommon disease and it is a variant of Guillain-Barre syndrome. Miller Fisher syndrome also has rarer variants.", "Miller Fisher syndrome is characterised by the triad ophthalmoparesis, ataxia and areflexia and is considered to be a variant of Guillain-Barré syndrome; its differential diagnosis includes Wernicke's encephalopathy.", "Miller Fisher syndrome is an acute inflammatory polyradiculoneuropathy that is generally considered a variant of Guillain-Barré syndrome and is characterized by the clinical triad of ataxia, areflexia, and ophthalmoplegia.", "Data were separately analysed for Miller Fisher syndrome and other Guillain-Barré syndrome variants.", "Guillain-Barré syndrome variants alone (excluding Miller Fisher syndrome) accounted for 10.5% of total cases.", "The syndrome of ataxia, areflexia and ophthalmoplegia, or Miller-Fisher syndrome, has been considered to be a variant of Guillain-Barré syndrome with pathology restricted to the peripheral nervous system." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/25072194", "http://www.ncbi.nlm.nih.gov/pubmed/16049921", "http://www.ncbi.nlm.nih.gov/pubmed/16645971", "http://www.ncbi.nlm.nih.gov/pubmed/9703176", "http://www.ncbi.nlm.nih.gov/pubmed/11155543", "http://www.ncbi.nlm.nih.gov/pubmed/1667714", "http://www.ncbi.nlm.nih.gov/pubmed/10965158", "http://www.ncbi.nlm.nih.gov/pubmed/16155441", "http://www.ncbi.nlm.nih.gov/pubmed/15012892", "http://www.ncbi.nlm.nih.gov/pubmed/8437011", "http://www.ncbi.nlm.nih.gov/pubmed/19810856", "http://www.ncbi.nlm.nih.gov/pubmed/10511801", "http://www.ncbi.nlm.nih.gov/pubmed/26380131", "http://www.ncbi.nlm.nih.gov/pubmed/19374296", "http://www.ncbi.nlm.nih.gov/pubmed/11521055", "http://www.ncbi.nlm.nih.gov/pubmed/24513384", "http://www.ncbi.nlm.nih.gov/pubmed/18428104", "http://www.ncbi.nlm.nih.gov/pubmed/26366317", "http://www.ncbi.nlm.nih.gov/pubmed/21325125", "http://www.ncbi.nlm.nih.gov/pubmed/22447677", "http://www.ncbi.nlm.nih.gov/pubmed/3612209", "http://www.ncbi.nlm.nih.gov/pubmed/15909003", "http://www.ncbi.nlm.nih.gov/pubmed/19263690" ]

[]

[]

[ "Yes. Ctf4 is associated with the replisome and is required for proper establishment of cohesion by facilitating cohesin acetylation." ]

[ "yes" ]

[ "In addition to Eco1, several other factors contribute to cohesion establishment, including Ctf4, Ctf18, Tof1, Csm3, Chl1 and Mrc1, but little is known about their roles. Here, we show that each of these factors facilitates cohesin acetylation. Moreover, the absence of Ctf4 and Chl1, but not of the other factors, causes a synthetic growth defect in cells lacking Eco1. Distinct from acetylation defects, sister chromatid cohesion in ctf4Δ and chl1Δ cells is not improved by removing Wapl", "Thus, Ctf4 and Chl1 delineate an additional acetylation-independent pathway that might hold important clues as to the mechanism of sister chromatid cohesion establishment", "Genetic analyses revealed that Rmi1 promoted sister chromatid cohesion in a process that was distinct from both the cohesion establishment pathway involving Ctf4, Csm3, and Chl1", "Influence of the human cohesion establishment factor Ctf4/AND-1", " Here, we used Xenopus egg extracts to show that AND-1 and Tim1-Tipin, homologues of Saccharomyces cerevisiae Ctf4 and Tof1-Csm3, respectively, are associated with the replisome and are required for proper establishment of the cohesion observed in the M-phase extracts", "These data defined two cohesion pathways, one containing CSM3, TOF1, CTF4, and CHL1, and the second containing MRC1, CTF18, CTF8, and DCC1", "Our results suggest that Chl1 and Ctf4 are directly involved in homologous recombination repair rather than acting indirectly via the establishment of sister chromatid cohesion", "Here we show that three proteins required for sister chromatid cohesion, Eco1, Ctf4, and Ctf18, are found at, and Ctf4 travels along chromosomes with, replication forks", "WSS1 was also found to interact genetically with SGS1, TOP3, SRS2 and CTF4, which are involved in recombination, repair of replication forks and the establishment of sister chromatid cohesion", "The catalytic subunit of budding yeast Polalpha (Pol1p) has been shown to associate in vitro with the Spt16p-Pob3p complex, a component of the nucleosome reorganization system required for both replication and transcription, and with a sister chromatid cohesion factor, Ctf4p", "Constituents of the replication fork, such as the DNA polymerase alpha-binding protein Ctf4, contribute to cohesion in ways that are poorly understood", "Genetic analyses revealed that Rmi1 promoted sister chromatid cohesion in a process that was distinct from both the cohesion establishment pathway involving Ctf4, Csm3, and Chl1 and the pathway involving the acetylation of Smc3.", "Our results suggest that Chl1 and Ctf4 are directly involved in homologous recombination repair rather than acting indirectly via the establishment of sister chromatid cohesion.", "Ctf4/AND-1 is a highly conserved gene product required for both DNA replication and the establishment of sister chromatid cohesion.", "Here we show that three proteins required for sister chromatid cohesion, Eco1, Ctf4, and Ctf18, are found at, and Ctf4 travels along chromosomes with, replication forks.", "Sister-chromatid cohesion mediated by the alternative RF-CCtf18/Dcc1/Ctf8, the helicase Chl1 and the polymerase-alpha-associated protein Ctf4 is essential for chromatid disjunction during meiosis II.", "Saccharomyces cerevisiae CTF18 and CTF4 are required for sister chromatid cohesion.", "We find that absence of either CTF4 or CTF18 causes sister chromatid cohesion failure and leads to a preanaphase accumulation of cells that depends on the spindle assembly checkpoint.", "We show here that CTF8, CTF4 and a helicase encoded by CHL1 are required for efficient sister chromatid cohesion in unperturbed mitotic cells, and provide evidence that Chl1 functions during S-phase.", "In budding yeast, a specialized replication factor C called RF-C(Ctf18/Dcc1/Ctf8) and the DNA-polymerase-alpha-associated protein Ctf4 are required to maintain sister-chromatid cohesion in cells arrested for long periods in mitosis.", "The physical and genetic interactions between CTF4, CTF18, and core components of replication fork complexes observed in this study and others suggest that both gene products act in association with the replication fork to facilitate sister chromatid cohesion.", "Our results suggest that Chl1 and Ctf4 are directly involved in homologous recombination repair rather than acting indirectly via the establishment of sister chromatid cohesion.", "Thus, Ctf4 and Chl1 delineate an additional acetylation-independent pathway that might hold important clues as to the mechanism of sister chromatid cohesion establishment.", "Thus, Ctf4 and Chl1 delineate an additional acetylation-independent pathway that might hold important clues as to the mechanism of sister chromatid cohesion establishment.", "Ctf4/AND-1 is a highly conserved gene product required for both DNA replication and the establishment of sister chromatid cohesion", "Genetic analyses revealed that Rmi1 promoted sister chromatid cohesion in a process that was distinct from both the cohesion establishment pathway involving Ctf4, Csm3, and Chl1 and the pathway involving the acetylation of Smc3", "Establishment of sister chromatid cohesion at the S. cerevisiae replication fork." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/11287619", "http://www.ncbi.nlm.nih.gov/pubmed/17483413", "http://www.ncbi.nlm.nih.gov/pubmed/15598824", "http://www.ncbi.nlm.nih.gov/pubmed/23334284", "http://www.ncbi.nlm.nih.gov/pubmed/19622120", "http://www.ncbi.nlm.nih.gov/pubmed/15485923", "http://www.ncbi.nlm.nih.gov/pubmed/20089864", "http://www.ncbi.nlm.nih.gov/pubmed/17222391", "http://www.ncbi.nlm.nih.gov/pubmed/16962805", "http://www.ncbi.nlm.nih.gov/pubmed/19496828", "http://www.ncbi.nlm.nih.gov/pubmed/15226378", "http://www.ncbi.nlm.nih.gov/pubmed/14742710", "http://www.ncbi.nlm.nih.gov/pubmed/23036200" ]

[]

[ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0034089", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0007062", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0007063", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0034087", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0045876", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0034085" ]

[ "The second parity rule (PR2), also known as Chargaff' s second parity rule, is an intra-strand rule which states that, when there are no biases between the two complementary strands of DNA in mutation and selection rates (substitution rates), complementary nucleotides are expected to have almost equal frequencies within single stranded DNA, namely A = T and G = C at equilibrium, without regard to the G + C content of the DNA." ]

[]

[ "Chargaff' s second parity rule (PR2) states that complementary nucleotides are met with almost equal frequencies in single stranded DNA.", "Sueoka and Lobry declared respectively that, in the absence of bias between the two DNA strands for mutation and selection, the base composition within each strand should be A=T and C=G (this state is called Parity Rule type 2, PR2)", "The intra-strand Parity Rule 2 of DNA (PR2) states that A=T and G=C within each strands.", "deviations from the PR2 is a sign of strand-specific (or asymmetric) mutation and/or selection pressures.", "PR2 is an intra-strand rule where A=T and G=C are expected when there are no biases between the two complementary strands of DNA in mutation and selection rates (substitution rates)", "When there are no biases in mutation and selection between the two strands of DNA, the 12 possible substitution rates of the four nucleotides reduces to six (type 1 parity rule or PR1), and the intrastrand average base composition is expected to be A = T and G = C at equilibrium without regard to the G + C content of DNA (type 2 parity rule or PR2)", "The second method was to plot the intrastrand bias of the third codon position from Parity Rule 2 (PR2), where A = T and G = C.", "The extent of deviation from intra-strand equality rule of A = T and G = C (Parity Rule 2, or PR2) is specific for individual amino acids and has been expressed as the PR2-bias fingerprint.", "When there are no biases in mutation and selection between the two strands of DNA, the 12 possible substitution rates of the four nucleotides reduces to six (type 1 parity rule or PR1), and the intrastrand average base composition is expected to be A = T and G = C at equilibrium without regard to the G + C content of DNA (type 2 parity rule or PR2).", "Chargaff s second parity rule (PR2) states that complementary nucleotides are met with almost equal frequencies in single stranded DNA.", "The second parity rule of Chargaff (AHT and GHC within one strand) holds all over the living world with minor exceptions.", "The second method was to plot the intrastrand bias of the third codon position from Parity Rule 2 (PR2), where A = T and G = C.", "The extent of deviation from intra-strand equality rule of A = T and G = C (Parity Rule 2, or PR2) is specific for individual amino acids and has been expressed as the PR2-bias fingerprint.", "Chargaff' s second parity rule (PR2) states that complementary nucleotides are met with almost equal frequencies in single stranded DNA", "The intra-strand Parity Rule 2 of DNA (PR2) states that A=T and G=C within each strands", "The second method was to plot the intrastrand bias of the third codon position from Parity Rule 2 (PR2), where A = T and G = C", "The extent of deviation from intra-strand equality rule of A = T and G = C (Parity Rule 2, or PR2) is specific for individual amino acids and has been expressed as the PR2-bias fingerprint" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/10570983", "http://www.ncbi.nlm.nih.gov/pubmed/7723058", "http://www.ncbi.nlm.nih.gov/pubmed/16893615", "http://www.ncbi.nlm.nih.gov/pubmed/10368434", "http://www.ncbi.nlm.nih.gov/pubmed/11164037", "http://www.ncbi.nlm.nih.gov/pubmed/14732869", "http://www.ncbi.nlm.nih.gov/pubmed/12468095", "http://www.ncbi.nlm.nih.gov/pubmed/10570985", "http://www.ncbi.nlm.nih.gov/pubmed/11675607", "http://www.ncbi.nlm.nih.gov/pubmed/19861381" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D010298" ]

[ "Gene therapy is one of the most promising and active fields in therapeutic research. Gene therapy is a treatment option that introduces genetic material in vivo or ex vivo into the cells of an affected organism in order to: exchange a defective gene; manipulate a disease-related gene; or introduce an additional gene copy for overexpression of the encoded protein to generate a curative biological effect. Somatic gene therapy is gene transfer by a specific vector to a somatic cell; in contrast to germline gene therapy, the modification of the cell is restricted to the recipient and cannot be passed to her/his progeny. High efficiency of gene transfer, high specificity for the target cells, long-lasting expression of the transgene and safety without adverse reactions are the desired characteristics of an ideal vector for gene transfer.\nRetroviral (gretroviral and lentiviral) vectors have now been used in more than 350 gene-therapy studies. Retroviral vectors are particularly suited for gene-correction of cells due to long-term and stable expression of the transferred transgene(s), and also because little effort is required for their cloning and production. Several monogenic inherited diseases, mostly immunodeficiencies, can now be successfully treated." ]

[ "yes" ]

[ "Several immunodeficiencies have been treated successfully by stem cell-targeted, retroviral-mediated gene transfer with reconstitution of the immune system following infusion of the transduced cells.", "In this work we have developed and tested a self-inactivating (SIN) gammaretroviral vector (SINfes.gp91s) containing a codon-optimized transgene (gp91(phox)) under the transcriptional control of a myeloid promoter for the gene therapy of the X-linked form of CGD (X-CGD).", " We used a lentiviral vector encoding functional WASP to genetically correct HSPCs from three WAS patients and reinfused the cells after a reduced-intensity conditioning regimen", "We used a lentiviral vector to transfer a functional ARSA gene into hematopoietic stem cells (HSCs) from three presymptomatic patients who showed genetic, biochemical, and neurophysiological evidence of late infantile MLD. ", "We assessed lentiviral vectors (LVs) targeted to the EC surface marker CD105 for in vivo gene delivery.", "gef and apoptin genes were cloned into a doxycycline-regulated retrovirus-mediated gene expression system." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/23921576", "http://www.ncbi.nlm.nih.gov/pubmed/23843498", "http://www.ncbi.nlm.nih.gov/pubmed/23884859", "http://www.ncbi.nlm.nih.gov/pubmed/23860311", "http://www.ncbi.nlm.nih.gov/pubmed/19435468", "http://www.ncbi.nlm.nih.gov/pubmed/21943326", "http://www.ncbi.nlm.nih.gov/pubmed/24120896", "http://www.ncbi.nlm.nih.gov/pubmed/23845947", "http://www.ncbi.nlm.nih.gov/pubmed/23845948", "http://www.ncbi.nlm.nih.gov/pubmed/23845071", "http://www.ncbi.nlm.nih.gov/pubmed/12686720", "http://www.ncbi.nlm.nih.gov/pubmed/16251873", "http://www.ncbi.nlm.nih.gov/pubmed/15912200" ]

[ { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C0598504", "o": "http://linkedlifedata.com/resource/umls/label/A1306652" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A1306651", "o": "gene transplantation for gene therapy" }, { "p": "http://data.linkedct.org/resource/linkedct/intervention_name", "s": "http://data.linkedct.org/resource/intervention/39568", "o": "Gene Therapy" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://data.linkedct.org/resource/intervention/39568", "o": "Intervention #39568 (Genetic:Gene Therapy)" }, { "p": "http://data.linkedct.org/resource/linkedct/intervention_name", "s": "http://data.linkedct.org/resource/intervention/17724", "o": "gene therapy" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://data.linkedct.org/resource/intervention/17724", "o": "Intervention #17724 (Procedure:gene therapy)" } ]

[ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005796", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012191", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012190", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0016458", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D015316", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0010467", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012192" ]

[ "Long non-coding RNAs (lncRNAs) are pervasively transcribed in the genome and are emerging as new players in tumorigenesis due to their various functions in transcriptional, posttranscriptional and epigenetic mechanisms of gene regulation. The best-studied examples include HOTAIR, a negative prognostic factor that exhibits pro-oncogenic activity in a variety of human cancers, CRNDE the gene symbol for Colorectal Neoplasia Differentially Expressed (non-protein-coding), a long non-coding RNA (lncRNA) gene that expresses multiple splice variants and displays a very tissue-specific pattern of expression and ANRIL, a lincRNA that is required for the PRC2 recruitment to and silencing of p15(INK4B) tumor suppressor gene." ]

[ "yes" ]

[ "Long non-coding RNA H19 increases bladder cancer metastasis", "These data suggest that upregulated H19 enhances bladder cancer metastasis by associating with EZH2 and inhibiting E-cad expression", "lncRNA H19 is essential for human tumor growth", "Previous reports have demonstrated that HOTAIR associates with chromatin modifications in cooperation with the Polycomb complex PRC2, and promotes breast and colorectal cancer metastasis", "although the clinical significance of HOTAIR expression in HCC may not be as pronounced as that in breast and colorectal cancers, the current study demonstrates that HOTAIR expression is associated with HCC progression, warranting further studies.", "Long non-coding RNA HOTAIR is an independent prognostic marker for nasopharyngeal carcinoma progression and survival", "Long non-coding RNA influences radiosensitivity of colorectal carcinoma cell lines by regulating cyclin D1 expression", "Long non-coding RNA urothelial carcinoma associated 1 (UCA1) promotes human bladder cancer cell proliferation, but the underlying mechanism remains unknown", "UCA1 regulated cell cycle through CREB via PI3K-AKT dependent pathway in bladder cancer.", "Long non-coding RNA UCA1 regulated cell cycle distribution via CREB through PI3-K dependent pathway in bladder carcinoma cells", "overexpression of Yiya promotes cell cycle progression at the G1/S transition, therefore identifying Yiya as a cell-cycle-associated long non-coding RNA", "The long noncoding RNA HOTAIR has been reported as a poor prognostic biomarker in patients with breast cancer. The aim of the present study is to examine the expression pattern of HOTAIR in hepatocellular carcinoma (HCC) and its clinical significance as well as its biological role in tumor progression", "The high expression level of HOTAIR in HCC could be a candidate biomarker for predicting tumor recurrence in HCC patients who have undergone liver transplant therapy and might be a potential therapeutic target", "Long non-coding RNA ANRIL is required for the PRC2 recruitment to and silencing of p15(INK4B) tumor suppressor gene", "A 42 kb region on human chromosome 9p21 encodes for three distinct tumor suppressors, p16(INK4A), p14(ARF) and p15(INK4B), and is altered in an estimated 30-40% of human tumors", "These results advance our understanding of the role of lncRNA-LET as a regulator of hypoxia signaling and offer new avenues for therapeutic intervention against cancer progression.", "Silencing MALAT1 is a potential novel therapeutic approach for this cancer." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/21991387", "http://www.ncbi.nlm.nih.gov/pubmed/22363342", "http://www.ncbi.nlm.nih.gov/pubmed/22493738", "http://www.ncbi.nlm.nih.gov/pubmed/23226159", "http://www.ncbi.nlm.nih.gov/pubmed/22454180", "http://www.ncbi.nlm.nih.gov/pubmed/23281836", "http://www.ncbi.nlm.nih.gov/pubmed/23354591", "http://www.ncbi.nlm.nih.gov/pubmed/22285928", "http://www.ncbi.nlm.nih.gov/pubmed/23443164", "http://www.ncbi.nlm.nih.gov/pubmed/21327457", "http://www.ncbi.nlm.nih.gov/pubmed/22258142", "http://www.ncbi.nlm.nih.gov/pubmed/23153939", "http://www.ncbi.nlm.nih.gov/pubmed/23208419", "http://www.ncbi.nlm.nih.gov/pubmed/23133536", "http://www.ncbi.nlm.nih.gov/pubmed/20393566", "http://www.ncbi.nlm.nih.gov/pubmed/21151178", "http://www.ncbi.nlm.nih.gov/pubmed/23267367", "http://www.ncbi.nlm.nih.gov/pubmed/22614017", "http://www.ncbi.nlm.nih.gov/pubmed/23292722", "http://www.ncbi.nlm.nih.gov/pubmed/23395002" ]

[]

[]

[ "Protein homeostasis, or proteostasis, refers to a proper balance between synthesis, maturation, and degradation of cellular proteins. Disruption of proteostasis is implicated in aging and the pathogenesis of numerous degenerative diseases." ]

[]

[ "Protein homeostasis, or proteostasis, refers to a proper balance between synthesis, maturation, and degradation of cellular proteins.", "Mechanisms that promote the homeostasis of the proteome, or proteostasis, can slow aging and decrease the incidence of age-related diseases.", "The eukaryotic cell possesses specialized pathways to turn over and degrade redundant proteins and organelles. Each pathway is unique and responsible for degradation of distinctive cytosolic material. The ubiquitin-proteasome system and autophagy (chaperone-mediated, macro, micro and organelle specific) act synergistically to maintain proteostasis. Defects in this equilibrium can be deleterious at cellular and organism level, giving rise to various disease states.", " protein homeostasis (proteostasis) ", "The folding biology common to all three kingdoms of life (Archaea, Bacteria, and Eukarya) is proteostasis. The proteostasis network (PN) functions as a “cloud” to generate, protect, and degrade the proteome.", "Maintaining the dynamic proteome of a living cell in the face of an ever-changing environment depends on a fine-tuned balance of protein synthesis and protein degradation. Molecular chaperones exert key functions during protein homeostasis (proteostasis). ", "This research highlighted the central importance of protein homeostasis, or proteostasis for short, defined as the cellular state in which the proteome is both stable and functional. It implicates an equilibrium between synthesis, folding, trafficking, aggregation, disaggregation and degradation.", "Protein homeostasis, also called proteostasis, is critical for cellular health and its dysregulation is implicated in aging, cancer, metabolic disease, and neurodegenerative disorders.", " protein homeostasis (proteostasis) ", " Disruption of proteostasis is implicated in aging and the pathogenesis of numerous degenerative diseases.", "Protein homeostasis, proteostasis, is essential to understand cell function. Protein degradation is a crucial component of the proteostatic mechanisms of the cell.", "Maintaining correct cellular function is a fundamental biological process for all forms of life. A critical aspect of this process is the maintenance of protein homeostasis (proteostasis) in the cell, which is largely performed by a group of proteins, referred to as the protein quality control (PQC) network. This network of proteins, comprised of chaperones and proteases, is critical for maintaining proteostasis not only during favourable growth conditions, but also in response to stress. ", "All organisms--Bacteria, Archaea and Eukarya--have evolved a protein homeostasis, or proteostasis, network comprising chaperones and folding factors, degradation components, signalling pathways and specialized compartmentalized modules that manage protein folding in response to environmental stimuli and variation. " ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/23463216", "http://www.ncbi.nlm.nih.gov/pubmed/24116849", "http://www.ncbi.nlm.nih.gov/pubmed/23986815", "http://www.ncbi.nlm.nih.gov/pubmed/23119163", "http://www.ncbi.nlm.nih.gov/pubmed/23479439", "http://www.ncbi.nlm.nih.gov/pubmed/23746257", "http://www.ncbi.nlm.nih.gov/pubmed/24126073", "http://www.ncbi.nlm.nih.gov/pubmed/24094931", "http://www.ncbi.nlm.nih.gov/pubmed/23833797", "http://www.ncbi.nlm.nih.gov/pubmed/23986914", "http://www.ncbi.nlm.nih.gov/pubmed/24079818", "http://www.ncbi.nlm.nih.gov/pubmed/23894132" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D057165" ]

[ "Genetic testing of the MTM1 gene can be used for the X-linked myotubular myopathy." ]

[ "MTM1 gene test" ]

[ "X-linked myotubular myopathy (MTM) is a severe neuromuscular disease of infancy caused by mutations of MTM1, which encodes the phosphoinositide lipid phosphatase, myotubularin", "As a gene for X linked MTM was recently identified in Xq28, we screened the obligatory carrier mothers for mutation. We found a 4 bp deletion in exon 4 of the MTM1 gene,", "X-linked Myotubular Myopathy has clearly shown the benefits to be gained from a multinational research consortium with a common interest in identifying and cloning the MTM1 gene.", "Myotubular myopathy (MTM1) is an X-linked disease, characterized by severe neonatal hypotonia and generalized muscle weakness, with pathological features suggesting an impairment in maturation of muscle fibres. The MTM1 gene encodes a protein (myotubularin) with a phosphotyrosine phosphatase consensus.", "myotubular myopathy (XLMTM), a severe congenital muscular disorder due to loss-of-function mutations in the MTM1 gene,", "We established a colony of dogs that harbor an X-linked MTM1 missense mutation.Muscle from affected male dogs exhibits reduction and altered localization of the MTM1 gene product, myotubularin, and provides a model analogous to X-linked myotubular myopathy (XLMTM)", "X-linked myotubular myopathy (XLMTM) is a rare congenital myopathy, usually characterized by severe hypotonia and respiratory insufficiency at birth, in affected, male infants. The disease is causally associated with mutations in the MTM1 gene, coding for phosphatase myotubularin.", "Mutations in the MTM1 gene encoding myotubularin cause X-linked myotubular myopathy (XLMTM), a well-defined subtype of human centronuclear myopathy.", "MTM1 gene sequencing revealed a unique exon 7 variant in all seven affected males, causing a nonconservative missense change, p.N155K, which haplotype data suggest derives from a recent founder in the local population.", "X-linked centronuclear myopathy (XLMTM), also called myotubular myopathy, is a severe congenital myopathy characterized by generalized hypotonia and weakness at birth and the typical histological finding of centralization of myo-nuclei. It is caused by mutations in the MTM1 gene encoding the 3-phosphoinositides phosphatase myotubularin.", "sequencing all MTM1 exons", "X-linked myotubular myopathy (XLMTM), a severe congenital disorder due to loss of function mutations in the MTM1 gene, encoding myotubularin, a phosphoinositide phosphatase thought to have a role in plasma membrane homeostasis and endocytosis.", "Mutations in the gene encoding the phosphoinositide phosphatase myotubularin 1 protein (MTM1) are usually associated with severe neonatal X-linked myotubular myopathy (XLMTM). However, mutations in MTM1 have also been recognized as the underlying cause of \"atypical\" forms of XLMTM in newborn boys, female infants, female manifesting carriers and adult men.", "X-linked myotubular myopathy (XLMTM), a recessive disorder, is caused by mutations affecting the myotubulatin (MTM1) gene located on the X chromosome. Most of the affected males die in the early postnatal period whereas female carriers are usually asymptomatic.", "The authors present a patient with the most severe X-linked recessive type (XLMTM).", "The diagnosis was confirmed and further specified by genetic analysis, revealing a novel frameshift mutation (1314-1315insT) of the myotubularin-coding MTM1 gene.", "X-linked myotubular myopathy (XLMTM) is a congenital muscle disorder caused by mutations in the MTM1 gene.", "MTM1, the gene encoding myotubularin (MTM1), is mutated in the X-linked myotubular myopathy (XLMTM), a severe genetic muscular disorder", "Myotubularin is a ubiquitously expressed phosphatase that acts on phosphatidylinositol 3-monophosphate [PI(3)P], a lipid implicated in intracellular vesicle trafficking and autophagy. It is encoded by the MTM1 gene, which is mutated in X-linked myotubular myopathy (XLMTM), a muscular disorder characterized by generalized hypotonia and muscle weakness at birth leading to early death of most affected males.", "The entire coding sequence of the gene was screened in 10 XLMTM patients using this technique.", "X-linked myotubular myopathy (XLMTM; OMIM# 310400) is a severe congenital muscle disease caused by mutations in the myotubularin (MTM1) gene.", "Mutations in the MTM1 gene cause X-linked recessive myotubular myopathy (XLMTM; MIM310400).", "We screened 29 independant patients with XLMTM phenotype and four with centronuclear myopathy. 87% (21/24) of patients with known MTM1 mutations showed abnormal myotubularin levels, including some with missense mutations.", "X-linked myotubular myopathy (XLMTM) characteristically causes severe or fatal muscle weakness in male infants. Mutations in the gene MTM1, encoding the protein myotubularin, can be identified in most families.", "X-linked myotubular myopathy (XLMTM) is a congenital muscular disease characterized by severe hypotonia and generalized muscle weakness, leading in most cases to early postnatal death. The gene responsible for the disease, MTM1, encodes a dual specificity phosphatase, named myotubularin, which is highly conserved throughout evolution.", "X-linked recessive myotubular myopathy (XLMTM) is a muscle disorder usually affecting newborn males. In the majority of cases, muscle weakness and hypotonia lead to a rapid demise at neonatal age. The responsible MTM1 gene is located in proximal Xq28.", "X-linked myotubular myopathy (XLMTM) is a severe congenital muscle disorder due to mutations in the MTM1 gene.", "X-linked recessive myotubular myopathy (XLMTM) is characterized by severe hypotonia and generalized muscle weakness, with impaired maturation of muscle fibres. The gene responsible, MTM1, was identified recently by positional cloning, and encodes a protein (myotubularin) with a tyrosine phosphatase domain (PTP).", "X-linked recessive myotubular myopathy (XLMTM; MTM1) is a severe neonatal disorder often causing perinatal death of the affected males. The responsible gene, designated MTM1, was localized to proximal Xq28 and recently isolated. The characterization of MTM1 allowed us to screen for causing mutations in three families, previously investigated by linkage analysis. Using exon amplification, single strand conformation polymorphism, and subsequent sequencing analysis, three new mutations and their mutational origin were characterized by analyzing 10 exons." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/17005396", "http://www.ncbi.nlm.nih.gov/pubmed/20434914", "http://www.ncbi.nlm.nih.gov/pubmed/10714588", "http://www.ncbi.nlm.nih.gov/pubmed/17621527", "http://www.ncbi.nlm.nih.gov/pubmed/9450905", "http://www.ncbi.nlm.nih.gov/pubmed/19084976", "http://www.ncbi.nlm.nih.gov/pubmed/8664565", "http://www.ncbi.nlm.nih.gov/pubmed/12391329", "http://www.ncbi.nlm.nih.gov/pubmed/20682747", "http://www.ncbi.nlm.nih.gov/pubmed/22068590", "http://www.ncbi.nlm.nih.gov/pubmed/12031625", "http://www.ncbi.nlm.nih.gov/pubmed/9736772", "http://www.ncbi.nlm.nih.gov/pubmed/9541111", "http://www.ncbi.nlm.nih.gov/pubmed/14660569", "http://www.ncbi.nlm.nih.gov/pubmed/11456308", "http://www.ncbi.nlm.nih.gov/pubmed/10063835", "http://www.ncbi.nlm.nih.gov/pubmed/18434328", "http://www.ncbi.nlm.nih.gov/pubmed/10323249", "http://www.ncbi.nlm.nih.gov/pubmed/19846786", "http://www.ncbi.nlm.nih.gov/pubmed/22987702", "http://www.ncbi.nlm.nih.gov/pubmed/22435031", "http://www.ncbi.nlm.nih.gov/pubmed/18358876", "http://www.ncbi.nlm.nih.gov/pubmed/23390130", "http://www.ncbi.nlm.nih.gov/pubmed/9781038", "http://www.ncbi.nlm.nih.gov/pubmed/9305655", "http://www.ncbi.nlm.nih.gov/pubmed/10502779", "http://www.ncbi.nlm.nih.gov/pubmed/23346162", "http://www.ncbi.nlm.nih.gov/pubmed/21488203", "http://www.ncbi.nlm.nih.gov/pubmed/11001925" ]

[ { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#type", "s": "http://linkedlifedata.com/resource/umls/label/A16765414", "o": "http://www.w3.org/2008/05/skos-xl#Label" }, { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#type", "s": "http://linkedlifedata.com/resource/umls/label/A10788614", "o": "http://www.w3.org/2008/05/skos-xl#Label" }, { "p": "http://linkedlifedata.com/resource/umls/altMetaMap", "s": "http://linkedlifedata.com/resource/umls/id/C0410203", "o": "http://linkedlifedata.com/resource/umls/label/A11987180" } ]

[ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D020914", "http://www.disease-ontology.org/api/metadata/DOID:14717", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005796" ]

[ "In biology, phylogenetics is the study of evolutionary relationships among groups of organisms (e.g. species, populations), which are discovered through molecular sequencing data and morphological data matrices. The result of phylogenetic studies is a hypothesis about the evolutionary history of taxonomic groups: their phylogeny. \nPhylogenetic analysis examines small differences in HIV’s genes using computational methods to calculate the genetic distance between strains. Unlike\nhuman DNA, which remains stable for a lifetime, HIV’s RNA changes very rapidly, leading to a huge amount of genetic diversity. This diversity means that scientists, using phylogenetic analysis, have been able to ascertain where HIV comes from, as well as track the various strains of HIV that exist worldwide.\nBased on results, there are found many studies on HIV phylogenetic analysis." ]

[ "yes" ]

[ "The results of Burst and phylogenetic analysis suggested that the C. neoformans var. grubii strains could be separated into three nonredundant evolutionary groups (Burst group 1 to group 3). ", "Phylogenetic trees were constructed to evaluate the relationships between the variants", "We analyzed pol (protease/reverse transcriptase) sequences from 135 newly diagnosed HIV-1-infected patients during the years 2009-2011. For phylogenetic relationships, sequences were aligned to the most recent reference data set from the Los Alamos database using BioEdit (version 7.1.3). The resulting alignment was analyzed with the Phylip package (version 3.67) building a neighbor-joining tree based on the Kimura two-parameter substitution model", ". Phylogenetic analysis of gag gene were then performed using the MEGA 3.1 software, the gene distances were calculated by Distance program. There were three different HIV-1 subtypes including B, CRF01-AE and CRF07-BC present among twenty four MSMs in Zhengzhou", "Phylogenetic analysis showed interpatient and intrapatient clustering of LTR nucleotide sequences.", " We evaluated the risk factors for intrafamilial transmission of HIV-1 infection through qualitative epidemiology following pol and env gene sequencing and phylogenetic analysis", "Phylogenetic analysis has shown that the Siberian 10.RU.6637 isolate displays the highest sequence identity to the HIV-1 subtype AG forms circulating in Uzbekistan", "Phylogenetic analysis showed that the evolutionary relationship of Env between HIV and SIV was the closest and they appeared to descend from a common ancestor, and the relationship of HIV and EIAV was the furthest", "DI was confirmed when maximum sequence divergence was excessive and supported by phylogenetic analysis", " (HIV-1) dual infection (DI) has been associated with decreased CD4 T-cell counts and increased viral loads; however, the frequency of intrasubtype DI is poorly understood.", "The aim of this study was to investigate the phylogenetic relationships of HIV-1 subtype C strains from Bangladesh and related strains from other countries, and thereby clarify when and from where subtype C was introduced in the country and how it subsequently spread within Bangladesh", " This study characterized HCV genotype 5 sequences from South Africa, including six near full-length genomes, as well as the E1 region from an additional 12 genotype 5 samples. Phylogenetic analysis of these near full-length genome sequences revealed that all genotype 5 sequences formed a close cluster with high bootstrap support", " The evolutionary history of the B subregion was not as clear as the C subregion, as the short length of this region yielded poor phylogenetic results", " Finally, a phylogenetic tree was constructed to elucidate the observed pattern of HIV TDR" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/24205972", "http://www.ncbi.nlm.nih.gov/pubmed/22981618", "http://www.ncbi.nlm.nih.gov/pubmed/22978157", "http://www.ncbi.nlm.nih.gov/pubmed/24273040", "http://www.ncbi.nlm.nih.gov/pubmed/23015735", "http://www.ncbi.nlm.nih.gov/pubmed/24223905", "http://www.ncbi.nlm.nih.gov/pubmed/22924643", "http://www.ncbi.nlm.nih.gov/pubmed/22899432", "http://www.ncbi.nlm.nih.gov/pubmed/19245688", "http://www.ncbi.nlm.nih.gov/pubmed/23555898", "http://www.ncbi.nlm.nih.gov/pubmed/24171696", "http://www.ncbi.nlm.nih.gov/pubmed/22162803", "http://www.ncbi.nlm.nih.gov/pubmed/24220189", "http://www.ncbi.nlm.nih.gov/pubmed/22903393", "http://www.ncbi.nlm.nih.gov/pubmed/23555203", "http://www.ncbi.nlm.nih.gov/pubmed/22996031", "http://www.ncbi.nlm.nih.gov/pubmed/22918554" ]

[ { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A7584997", "o": "C18940" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A7584997", "o": "Phylogenetics" }, { "p": "http://linkedlifedata.com/resource/umls/prefMetaMap", "s": "http://linkedlifedata.com/resource/umls/id/C1519068", "o": "http://linkedlifedata.com/resource/umls/label/A7658697" }, { "p": "http://www.w3.org/2008/05/skos-xl#prefLabel", "s": "http://linkedlifedata.com/resource/umls/id/C1519068", "o": "http://linkedlifedata.com/resource/umls/label/A7658697" }, { "p": "http://linkedlifedata.com/resource/umls/altMetaMap", "s": "http://linkedlifedata.com/resource/umls/id/C1519068", "o": "http://linkedlifedata.com/resource/umls/label/A7584997" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A7658697", "o": "Phylogenetic Analysis" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A7658697", "o": "C18940" }, { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A7584997", "o": "NCI Thesaurus" }, { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A7658697", "o": "NCI Thesaurus" } ]

[ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D006678", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D010802", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D058974" ]