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[ "Nucleotide Excision Repair (NER) removes a variety of helix-distorting lesions from DNA. It has two sub-pathways, the global genome (gg) NER and the transcription-coupled repair (TCR). TCR is triggered when a RNA polymerase, translocating along the transcribed strand, is arrested at a lesion or unusual structure in the DNA. TCR is dedicated to target and repair the transcribed strand of an active gene." ]

[ "the transcribed strand" ]

[ "Transcription-coupled repair (TCR) is the major pathway involved in the removal of UV-induced photolesions from the transcribed strand of active genes.", "transcription-coupled repair (TCR) provides faster repair of the transcribed strand of active genes.", "there are two sub-pathways of nucleotide excision repair (NER), the global genome (gg) NER and the transcription-coupled repair (TCR). TCR can preferentially remove the bulky DNA lesions located at the transcribed strand of a transcriptional active gene more rapidly than those at the untranscribed strand or overall genomic DNA.", "transcription-coupled repair (TCR) since targets for DNA damage are situated on the transcribed or coding strand of DNA", "Nucleotide Excision Repair (NER), which removes a variety of helix-distorting lesions from DNA, is initiated by two distinct DNA damage-sensing mechanisms. Transcription Coupled Repair (TCR) removes damage from the active strand of transcribed genes", "Transcription-coupled repair (TCR) is a sub-pathway of nucleotide excision repair that allows for the enhanced repair of the transcribed strand of active genes.", "Transcription coupled repair (TCR) is a nucleotide excision repair (NER) pathway that is dedicated to repair in the transcribed strand of an active gene.", "Transcription-coupled repair (TCR) is a pathway dedicated to the removal of damage from the template strands of actively transcribed genes.", "Although the detailed mechanism of TCR is not yet understood, it is believed to be triggered when a translocating RNA polymerase is arrested at a lesion or unusual structure in the DNA.", "Among these is a process called transcription-coupled repair (TCR) that catalyzes the removal of DNA lesions from the transcribed strand of expressed genes, often resulting in a preferential bias of damage clearance from this strand relative to its non-transcribed counterpart.", "These results suggest that UV treatment results in an induced repair of UV-damaged DNA in the transcribed strand of an active gene in XP-C and normal cells through an enhancement of TCR or a mechanism which involves the TCR pathway.", "TCR can preferentially remove the bulky DNA lesions located at the transcribed strand of a transcriptional active gene more rapidly than those at the untranscribed strand or overall genomic DNA.", "The proficient repair of the nontranscribed strand cannot be explained by the dedicated subpathway of transcription-coupled repair (TCR), which is targeted to the transcribed strand in expressed genes.", "Transcription-coupled repair (TCR) is a universal sub-pathway of the nucleotide excision repair (NER) system that is limited to the transcribed strand of active structural genes.", "NER can operate via two subpathways: global genome repair (GGR) and a specialized pathway coupled to active transcription (transcription-coupled repair, TCR) and directed to DNA lesions in the transcribed strand of active genes.", "Transcription coupled repair (TCR), a special sub-pathway of nucleotide excision repair (NER), removes transcription blocking lesions rapidly from the transcribing strand of active genes.", "Transcription-coupled repair (TCR) acts solely on the transcribed strand of expressed genes, while global genomic repair (GGR) is responsible for the ubiquitous repair of the genome.", "In addition to the recognition and excision of DNA damage throughout the genome (GGR), there exists a mechanism, transcription-coupled nucleotide excision repair (TCR), for recognizing some types of DNA damage in the transcribed strand of genes in Escherichia coli, yeast and mammalian cells.", "The proficient repair of the nontranscribed strand cannot be explained by the dedicated subpathway of transcription-coupled repair (TCR), which is targeted to the transcribed strand in expressed genes.", "TCR can preferentially remove the bulky DNA lesions located at the transcribed strand of a transcriptional active gene more rapidly than those at the untranscribed strand or overall genomic DNA.", "Transcription-coupled repair (TCR) is a subpathway of nucleotide excision repair (NER) that acts specifically on lesions in the transcribed strand of expressed genes.", "The blockage of transcription elongation by RNA polymerase II (pol II) at a DNA damage site on the transcribed strand triggers a transcription-coupled DNA repair (TCR), which rapidly removes DNA damage on the transcribed strand of the expressed gene and allows the resumption of transcription.", "It has been previously shown that disruption of RAD26 in yeast strain W303-1B results in a strain that is deficient in transcription-coupled repair (TCR), the preferential repair of the transcribed strand of an expressed gene over the non-transcribed strand and the rest of the genome.", "The proficient repair of the nontranscribed strand cannot be explained by the dedicated subpathway of transcription-coupled repair (TCR), which is targeted to the transcribed strand in expressed genes", "A dedicated excision repair pathway, termed transcription-coupled repair (TCR), targets the removal of DNA lesions from transcribed strands of expressed genes", "NER can operate via two subpathways: global genome repair (GGR) and a specialized pathway coupled to active transcription (transcription-coupled repair, TCR) and directed to DNA lesions in the transcribed strand of active genes", "Transcription coupled repair (TCR) is a nucleotide excision repair (NER) pathway that is dedicated to repair in the transcribed strand of an active gene", "Transcription-coupled repair (TCR) is generally observed as more rapid or more efficient removal of certain types of DNA damage from the transcribed strands of expressed genes compared with the nontranscribed strands", "In addition to the recognition and excision of DNA damage throughout the genome (GGR), there exists a mechanism, transcription-coupled nucleotide excision repair (TCR), for recognizing some types of DNA damage in the transcribed strand of genes in Escherichia coli, yeast and mammalian cells" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/18817898", "http://www.ncbi.nlm.nih.gov/pubmed/8807287", "http://www.ncbi.nlm.nih.gov/pubmed/12142466", "http://www.ncbi.nlm.nih.gov/pubmed/10637337", "http://www.ncbi.nlm.nih.gov/pubmed/9637246", "http://www.ncbi.nlm.nih.gov/pubmed/11821423", "http://www.ncbi.nlm.nih.gov/pubmed/15380101", "http://www.ncbi.nlm.nih.gov/pubmed/7957102", "http://www.ncbi.nlm.nih.gov/pubmed/9288788", "http://www.ncbi.nlm.nih.gov/pubmed/14734564", "http://www.ncbi.nlm.nih.gov/pubmed/17893751", "http://www.ncbi.nlm.nih.gov/pubmed/22902626", "http://www.ncbi.nlm.nih.gov/pubmed/20463888", "http://www.ncbi.nlm.nih.gov/pubmed/11182543", "http://www.ncbi.nlm.nih.gov/pubmed/15913669", "http://www.ncbi.nlm.nih.gov/pubmed/17015469", "http://www.ncbi.nlm.nih.gov/pubmed/14599741", "http://www.ncbi.nlm.nih.gov/pubmed/14599769", "http://www.ncbi.nlm.nih.gov/pubmed/9065408", "http://www.ncbi.nlm.nih.gov/pubmed/8972850", "http://www.ncbi.nlm.nih.gov/pubmed/9934845", "http://www.ncbi.nlm.nih.gov/pubmed/16158195", "http://www.ncbi.nlm.nih.gov/pubmed/18291710", "http://www.ncbi.nlm.nih.gov/pubmed/9150262", "http://www.ncbi.nlm.nih.gov/pubmed/22749141", "http://www.ncbi.nlm.nih.gov/pubmed/21466822", "http://www.ncbi.nlm.nih.gov/pubmed/16394029", "http://www.ncbi.nlm.nih.gov/pubmed/15186415", "http://www.ncbi.nlm.nih.gov/pubmed/21214942", "http://www.ncbi.nlm.nih.gov/pubmed/11452033", "http://www.ncbi.nlm.nih.gov/pubmed/20978633", "http://www.ncbi.nlm.nih.gov/pubmed/19381941", "http://www.ncbi.nlm.nih.gov/pubmed/16978026", "http://www.ncbi.nlm.nih.gov/pubmed/15249207", "http://www.ncbi.nlm.nih.gov/pubmed/12509290" ]

[]

[ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0090262", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D052416", "http://www.uniprot.org/uniprot/MFD_STAAM", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0006283" ]

[ "chromosomes 3, 6, 8, 12, 15, 17, 21, X and Y were implicated in the Moyamoya disease." ]

[ "3", "6", "8", "12", "15", "17", "21", "X", "Y" ]

[ "Complex chromosome rearrangement of 6p25.3->p23 and 12q24.32->qter in a child with moyamoya.", "Routine karyotype demonstrated extra chromosomal material on 6p. Single nucleotide polymorphism microarray revealed a previously unreported complex de novo genetic rearrangement involving subtelomeric segments on chromosomes 6p and 12q.", "In terms of the genetics, recent literature suggests a low penetrance autosomal dominant or polygenic mode of transmission involving chromosomes 3, 6, 8, 12, and 17 for familial MMD. ", "Furthermore, the current literature on familial MMD has pointed to a low penetrance autosomal dominant or polygenic mode of transmittance at loci on chromosomes 3, 6, 8, 12, and 17.", "Here, we report on three unrelated families affected with an X-linked moyamoya syndrome characterized by the association of a moyamoya angiopathy, short stature, and a stereotyped facial dysmorphism. ", "We show that this syndromic moyamoya is caused by Xq28 deletions removing MTCP1/MTCP1NB and BRCC3. ", "A genome-wide association study of 785,720 single-nucleotide polymorphisms (SNPs) was performed, comparing 72 Japanese MMD patients with 45 Japanese controls and resulting in a strong association of chromosome 17q25-ter with MMD risk. This result was further confirmed by a locus-specific association study using 335 SNPs in the 17q25-ter region. ", "Investigations included neuroimaging, cardiologic and ophthalmologic evaluation, hormonal testing, hemoglobin electrophoresis, chromosomal karyotyping, muscle biopsy for morphology, immunohistochemistry and enzyme assays, mtDNA mutation screening, and haplotype analysis of 2 loci previously linked to moyamoya, on chromosomes 10 (ACTA2) and 17.", "These data strongly suggest that this family is affected by a hereditary moyamoya multisystem disorder with X-linked recessive pattern of inheritance.", "Her features were consistent with TS and chromosome analysis revealed mosaicism in which 17% of the cells showed a pseudoisodicentric Y chromosome: 45,X (25)/46,X psu idic (Y)(11.2) (5). ", "The small number of cases does not allow detailed analysis other than noting patient age (two older than 40 years), karyotype (two others associated with isochrome Xq), and associated cardiac risk factors (one with BAV).", " Studies have shown a possible genetic association of MMD linked to chromosome 17 in Japanese cases as well as in cases found in other demographics. ", "The gene responsible for NF1 is located on the chromosome region 17q11.2 and for familial moyamoya disease on chromosome 17q25. ", "Autosomal dominant moyamoya disease maps to chromosome 17q25.3.", "Under both classifications, significant evidence of linkage was only observed on chromosome 17q25.3, with maximum multipoint logarithm of odds (lod) scores of 6.57 (under the narrow classification) and 8.07 (under the broad classification) at D17S704. Haplotype analysis revealed segregation of a disease haplotype in all families but one, and informative crossovers enabled mapping of the MMD locus to a 3.5-Mb region between D17S1806 and the telomere of 17q, encompassing 94 annotated genes. CONCLUSIONS: Our data suggest that there is a major gene locus for autosomal dominant moyamoya disease on chromosome 17q25.3.", "However, the mitochondrial DNA and Y chromosomal genotype showed that affected members had the same sequence of the Mitochondrial 3 portion of D-loop with Japanese patients. ", "Smith-Magenis syndrome and Moyamoya disease in a patient with del(17)(p11.2p13.1).", "We have employed a combination of aCGH, FISH, and MLPA to characterize an approximately 6.3 Mb deletion spanning chromosome region 17p11.2-p13.1 in this patient, with the proximal breakpoint within the RAI1 gene. ", "Moyamoya syndrome in a child with trisomy 12p syndrome.", "This report presents the first case of moyamoya syndrome with trisomy 12p with a familial pericentric inversion of chromosome 12.", " She had been prenatally diagnosed with trisomy 12p with a familial pericentric inversion of chromosome 12 originating from her mother. She manifested developmental delay and some dysmorphic features of the face and limbs compatible with the clinical features of trisomy 12p.", "The genes encoding tissue inhibitor of metalloproteinase (TIMP) 4 and TIMP2 span chromosomes 3p24.2-p26 and 17q25, respectively, which are the locations of familial moyamoya disease (FMMD) genes. ", "We postulate that a protein encoded on chromosome 21 may be related to the pathogenesis of Down's syndrome with moyamoya syndrome.", "[Molecular screening for moyamoya disease by use of expressed sequence tag on chromosome 3p].", " To identify the expressed sequence tags (ESTs) with monoallelic expressions on chromosome 3, we used mouse A9 hybrid cells having human chromosome 3. Two ESTs showed only maternal expression in mouse A9 hybrid cells, and four showed non-expression in the lymphocytes derived from moyamoya patients. ", "A novel susceptibility locus for moyamoya disease on chromosome 8q23.", "Previous linkage studies have indicated that susceptibility loci for the disease are located on chromosomes 3p, 6q, and 17q. In the present study, we searched for loci linked to the disease in 12 Japanese families using 428 microsatellite markers and found significant evidence for linkage to 8q23 [maximum LOD score (MLS) of 3.6] and suggestive evidence for linkage to 12p12 (MLS=2.3). ", "Considering the function, we selected nine genes as candidates from a total of 65 genes identified in the 9-cM region of D17S785-D17S836 in chromosome 17q25, and performed sequence analysis on the DNA samples obtained from a pedigree of familial moyamoya disease, which showed a complete linkage to the region by a haplotype analysis. ", "Linkage of familial moyamoya disease (spontaneous occlusion of the circle of Willis) to chromosome 17q25.", "The characteristic lesions of moyamoya disease are occasionally seen in neurofibromatosis type 1, of which the causative gene (NF1) has been assigned to chromosome 17q11.2.", "CONCLUSIONS: A gene for familial moyamoya disease is located on chromosome 17q25.", "Recent genetic studies suggest some responsible genetic foci in chromosomes 3, 6 and 17.", "To further specify the genetic component of moyamoya disease, a linkage study of moyamoya disease using markers on chromosome 6, where the HLA gene is located, was performed. ", "Mapping of a familial moyamoya disease gene to chromosome 3p24.2-p26.", "A linkage was found between the disease and markers located at 3p24.2-26.", "We postulate that a protein encoded on chromosome 21 may be related to the pathogenesis of moyamoya disease. ", "The diagnosis of PWS was confirmed genetically by the method of fluorescence in situ hybridization which showed the deletion of chromosome 15. " ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/10754001", "http://www.ncbi.nlm.nih.gov/pubmed/23713105", "http://www.ncbi.nlm.nih.gov/pubmed/22426657", "http://www.ncbi.nlm.nih.gov/pubmed/15340753", "http://www.ncbi.nlm.nih.gov/pubmed/16164190", "http://www.ncbi.nlm.nih.gov/pubmed/23966756", "http://www.ncbi.nlm.nih.gov/pubmed/22436252", "http://www.ncbi.nlm.nih.gov/pubmed/21968521", "http://www.ncbi.nlm.nih.gov/pubmed/11037190", "http://www.ncbi.nlm.nih.gov/pubmed/17431895", "http://www.ncbi.nlm.nih.gov/pubmed/15675355", "http://www.ncbi.nlm.nih.gov/pubmed/20644152", "http://www.ncbi.nlm.nih.gov/pubmed/18576213", "http://www.ncbi.nlm.nih.gov/pubmed/24167642", "http://www.ncbi.nlm.nih.gov/pubmed/10757474", "http://www.ncbi.nlm.nih.gov/pubmed/9128751", "http://www.ncbi.nlm.nih.gov/pubmed/9973290", "http://www.ncbi.nlm.nih.gov/pubmed/19335127", "http://www.ncbi.nlm.nih.gov/pubmed/8898827", "http://www.ncbi.nlm.nih.gov/pubmed/21596366", "http://www.ncbi.nlm.nih.gov/pubmed/15675354", "http://www.ncbi.nlm.nih.gov/pubmed/20635402", "http://www.ncbi.nlm.nih.gov/pubmed/18463369", "http://www.ncbi.nlm.nih.gov/pubmed/23077562", "http://www.ncbi.nlm.nih.gov/pubmed/16475235", "http://www.ncbi.nlm.nih.gov/pubmed/19918425", "http://www.ncbi.nlm.nih.gov/pubmed/17138018", "http://www.ncbi.nlm.nih.gov/pubmed/18174554", "http://www.ncbi.nlm.nih.gov/pubmed/15362573", "http://www.ncbi.nlm.nih.gov/pubmed/8937199", "http://www.ncbi.nlm.nih.gov/pubmed/21631222", "http://www.ncbi.nlm.nih.gov/pubmed/16723886", "http://www.ncbi.nlm.nih.gov/pubmed/21048783" ]

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[ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009072", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D002875", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0005694", "http://www.disease-ontology.org/api/metadata/DOID:13099", "http://www.disease-ontology.org/api/metadata/DOID:0080014" ]

[ "The branch site consensus sequence in U12-dependent introns is UUCCUUAAC." ]

[ "UUCCUUAAC" ]

[ "Highly conserved sequences at the 5' splice site and branch site of U12-dependent introns are important determinants for splicing by U12-dependent spliceosomes. This study investigates the in vivo splicing phenotypes of mutations in the branch site consensus sequence of the U12-dependent intron F from a human NOL1 (P120) minigene. Intron F contains a fully consensus branch site sequence (UUCCUUAAC). ", "Intron F contains a fully consensus branch site sequence (UUCCUUAAC).", "Intron F contains a fully consensus branch site sequence (UUCCUUAAC)" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/18824513" ]

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[ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016384", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0005689", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0000348", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0005693", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D032921", "http://www.uniprot.org/uniprot/PM14_HUMAN", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D007438", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0071017", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0071015", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0030626" ]

[ "Protein A from the bacterium Staphylococcus aureus (SpA) is used as an affinity ligand for purification of immunoglobulin G (IgG)." ]

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[ "Staphylococcal protein A (SpA) binds Fcγ and VH3 clan Fab domains of human and animal immunoglobulin (Ig) with each of its five Ig binding domains (IgBDs),", "Protein A from Staphylococcus aureus plays one key role as an immobilized affinity ligand for the purification of antibodies. ", "The recombinant SpA is also widely used in biotechnology to purify polyclonal and monoclonal immunoglobulin G antibodies.", "Staphylococcus aureus protein A (SpA) is the most popular affinity ligand for immunoglobulin G1 (IgG1).", "Staphylococcal Protein A (SPA), a cell wall protein of Staphylococcus aureus, is in high demand because of its ability to bind immunoglobulins.", "Protein A from the bacterium Staphylococcus aureus (SpA) has been widely used as an affinity ligand for purification of immunoglobulin G (IgG). ", "Affinity chromatography with protein A from Staphylococcus aureus (SpA) is the most widespread and accepted methodology for antibody capture during the downstream process of antibody manufacturing", "Affinity chromatography using protein A from Staphylococcus aureus as the ligand has been widely used for the isolation of immunoglobulin G (IgG) from various species." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/22136061", "http://www.ncbi.nlm.nih.gov/pubmed/24184233", "http://www.ncbi.nlm.nih.gov/pubmed/22621885", "http://www.ncbi.nlm.nih.gov/pubmed/24033345", "http://www.ncbi.nlm.nih.gov/pubmed/12472184", "http://www.ncbi.nlm.nih.gov/pubmed/23776704", "http://www.ncbi.nlm.nih.gov/pubmed/24291195", "http://www.ncbi.nlm.nih.gov/pubmed/23770556" ]

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[ "http://www.uniprot.org/uniprot/SRAP_STAAU", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013211", "http://www.uniprot.org/uniprot/SRAP_STAAW" ]

[ "The activity of TLC G-65 (a liposomal gentamicin preparation), alone and in combination with rifapentine, clarithromycin, clofazimine and ethambutol, was evaluated in the beige mouse (C57BL/6J--bgj/bgj) model of disseminated Mycobacterium avium infection. TLC G-65 in combination with rifapentine appears to be an attractive regimen for the treatment of infections caused by bacteria in the M. avium complex. Rifampin 10 mg/kg daily, ciprofloxacin 500 mg twice daily, clofazimine 100 mg every day, and ethambutol 15 mg/kg orally daily for 24 weeks, with or without amikacin 10 mg/kg intravenously or intramuscularly 5 days weekly for the first 4 weeks. In vivo phage treatment may also be used in some cases.", "Rifampin 10 mg/kg daily, ciprofloxacin 500 mg twice daily, clofazimine 100 mg every day, and ethambutol 15 mg/kg orally daily for 24 weeks, with or without amikacin 10 mg/kg intravenously or intramuscularly 5 days weekly for the first 4 weeks", "The activity of TLC G-65 (a liposomal gentamicin preparation), alone and in combination with rifapentine, clarithromycin, clofazimine and ethambutol, was evaluated in the beige mouse (C57BL/6J--bgj/bgj) model of disseminated Mycobacterium avium infection" ]

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[ "The activity of TLC G-65 (a liposomal gentamicin preparation), alone and in combination with rifapentine, clarithromycin, clofazimine and ethambutol, was evaluated in the beige mouse (C57BL/6J--bgj/bgj) model of disseminated Mycobacterium avium infection", "TLC G-65 in combination with rifapentine appears to be an attractive regimen for the treatment of infections caused by bacteria in the M. avium complex.", "Rifampin 10 mg/kg daily, ciprofloxacin 500 mg twice daily, clofazimine 100 mg every day, and ethambutol 15 mg/kg orally daily for 24 weeks, with or without amikacin 10 mg/kg intravenously or intramuscularly 5 days weekly for the first 4 weeks", "TM4 is a lytic mycobacteriophage that kills both extracellular M. avium and M. tuberculosis. When delivered by M. smegmatis transiently infected with TM4, it kills both M. avium and M. tuberculosis within RAW 264.7 macrophages.", "The patient was commenced on a 3-drug regimen with rifabutin, ethambutol and clarithromycin and has remained asymptomatic now for over 9 months. ", "A randomized, double-blind trial comparing azithromycin and clarithromycin in the treatment of disseminated Mycobacterium avium infection in patients with human immunodeficiency virus.", "Activity of clarithromycin against Mycobacterium avium infection in patients with the acquired immune deficiency syndrome. ", "Evolution was favorable with multiple-drug therapy including rifampicin, ethambutol, and clarithromycin, along with a slight reduction in immunosuppression.", "The turning point in antimicrobial therapy of Mycobacterium avium infections came with the development of two new macrolides, clarithromycin and azithromycin.", "Clarithromycin against Mycobacterium avium complex infections." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/19929882", "http://www.ncbi.nlm.nih.gov/pubmed/1832527", "http://www.ncbi.nlm.nih.gov/pubmed/9875582", "http://www.ncbi.nlm.nih.gov/pubmed/11073759", "http://www.ncbi.nlm.nih.gov/pubmed/1387133", "http://www.ncbi.nlm.nih.gov/pubmed/10714126", "http://www.ncbi.nlm.nih.gov/pubmed/16584300", "http://www.ncbi.nlm.nih.gov/pubmed/8733409" ]

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[ "A multidisciplinary approach is frequently necessary to treat acute pericarditis; the most frequent treatments are: antiinflammatory steroid and non-steroid drugs, antibiotic therapy, pericardial drainage and, less frequently ,intrapericardial irrigation of fibrinolytics; antituberculous chemotherapy in presence of Tuberculous Agent" ]

[]

[ "Recurrences develop in up to 20-50% of patients with acute pericarditis. Although different causes of recurrent pericarditis have been identified, the etiology remains obscure in most cases which are therefore labelled as idiopathic.", "A poor response to colchicine treatment and/or a steroid-dependence may be the clue to investigate TNFRSF1A mutations in patients with idiopathic recurrent pericarditis.", "intravenous infusion of inotropic agents", "medical treatment may be changed in these patients with a slower tapering of the dosage of steroidal and non-steroidal antiinflammatory drugs.", "The incidence of purulent pericarditis has decreased considerably since the antibiotic era. It is typically an acute and potentially lethal disease, necessitating rapid diagnosis and adequate therapy to improve prognosis. Standard treatment combines appropriate antibiotic therapy with surgical drainage.", "We report successful treatment of a non-resolving fibrino-purulent pericardial effusion by combined intrapericardial irrigation of fibrinolytics and systemic corticosteroids administration as an alternative to pericardectomy.", "Prednisolone (20-30 mg/d) was used in addition to antituberculous chemotherapy in 11 of the 17 patients with effusive pericarditis", "antibiotic therapy has been initiated. Use of appropriate parenterally administered antibiotics, in combination with early surgical pericardial drainage or partial pericardiectomy, should minimize morbidity and mortality and prevent acute constrictive sequelae." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/18924029", "http://www.ncbi.nlm.nih.gov/pubmed/10560235", "http://www.ncbi.nlm.nih.gov/pubmed/12405580", "http://www.ncbi.nlm.nih.gov/pubmed/17415329", "http://www.ncbi.nlm.nih.gov/pubmed/12379412", "http://www.ncbi.nlm.nih.gov/pubmed/6966005", "http://www.ncbi.nlm.nih.gov/pubmed/7375968", "http://www.ncbi.nlm.nih.gov/pubmed/6727432", "http://www.ncbi.nlm.nih.gov/pubmed/10920507", "http://www.ncbi.nlm.nih.gov/pubmed/6726718", "http://www.ncbi.nlm.nih.gov/pubmed/308705" ]

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[ "The genetic basis of tuberous sclerosis has been attributed to mutations in one of two unlinked genes, TSC1 and TSC2. The functions of the TSC1 and TSC2 gene products, hamartin and tuberin, respectively, have remained ill defined until recently. Genetic, biochemical, and biologic analyses have highlighted their role as negative regulators of the mTOR signaling pathway. Tuberin, serving as a substrate of AKT and AMPK, mediates mTOR activity by coordinating inputs from growth factors and energy availability in the control of cell growth, proliferation, and survival. Emerging evidence also suggests that the TSC 1/2 complex may play a role in modulating the activity of beta-catenin and TGFbeta. These findings provide novel functional links between the TSC genes and other tumor suppressors.", "The genetic basis of this disease has been attributed to mutations in one of two unlinked genes, TSC1 and TSC2.", "We previously found TSC2 loss of heterozygosity in 7 of 13 (54%) of angiomyolipomas from sporadic LAM patients, suggesting that LAM and TSC could have a common genetic basis. In this study, we report the identification of somatic TSC2 mutations in five of seven angiomyolipomas from sporadic LAM patients. Our data demonstrate that somatic mutations in the TSC2 gene occur in the angiomyolipomas and pulmonary LAM cells of women with sporadic LAM, strongly supporting a direct role of TSC2 in the pathogenesis of this disease. The study of hereditary tumor syndromes has laid a solid foundation toward understanding the genetic basis of cancer." ]

[ "TSC1 and TSC2 genes" ]

[ "The genetic basis of this disease has been attributed to mutations in one of two unlinked genes, TSC1 and TSC2.", "The functions of the TSC1 and TSC2 gene products, hamartin and tuberin, respectively, have remained ill defined until recently", "Genetic, biochemical, and biologic analyses have highlighted their role as negative regulators of the mTOR signaling pathway. Tuberin, serving as a substrate of AKT and AMPK, mediates mTOR activity by coordinating inputs from growth factors and energy availability in the control of cell growth, proliferation, and survival. Emerging evidence also suggests that the TSC 1/2 complex may play a role in modulating the activity of beta-catenin and TGFbeta. These findings provide novel functional links between the TSC genes and other tumor suppressors", "Ten years ago, a mutation in the TSC2 gene was identified in the Eker rat at Fox Chase Cancer Center by Yeung and Knudson, and in Tokyo by Kobayashi and Hino.", "Here, we will review the clinical association of RCC in TSC, consider the factors that have led to its under-emphasis within the RCC field, address the cellular and biochemical mechanisms that may contribute to RCC in cells with TSC1 or TSC2 mutations, and finally discuss the ways in which the TSC signaling pathways may be linked to sporadic RCC in the general population.", "Either of two genes, TSC1 or TSC2, can be mutated, resulting in the tuberous sclerosis complex phenotype.", "The protein products of the tuberous sclerosis complex genes, hamartin (TSC1) and tuberin (TSC2), have been discovered to play important roles in several cell-signaling pathways", "Knowledge regarding the function of the tuberin-hamartin complex has led to therapeutic intervention trials. ", "TSC2 mutations were identified in all cyst-positive patients who were tested (n = 8), whereas both TSC1 and TSC2 mutations were found in patients with nodular disease.", "We previously found TSC2 loss of heterozygosity in 7 of 13 (54%) of angiomyolipomas from sporadic LAM patients, suggesting that LAM and TSC could have a common genetic basis.", "Mutations in the tuberous sclerosis complex gene TSC2 are a cause of sporadic pulmonary lymphangioleiomyomatosis", "The disease can be caused by mutations in either of two genes, TSC2, identified in 1993, and TSC1, only recently identified.", "Molecular genetic basis of renal carcinogenesis in the Eker rat model of tuberous sclerosis (Tsc2)", "We have recently identified on rat chromosome 10q a germline mutation in the tuberous sclerosis gene (Tsc2), the gene predisposing to renal carcinoma (RC) in the Eker rat", "Tuberous sclerosis complex is a genetic disorder caused by mutations in either the TSC1 or TSC2 gene that can result in the growth of hamartomas in multiple organ systems", "Striking improvements in the understanding of the genetic basis of this autosomal dominant genetic disease are coupled to the understanding of the mechanisms that link the loss of TSC1 (9q34) or TSC2 (16p13.3) genes with the regulation of the Rheb/m-TOR/p70S6K pathway. ", "In all these lesions, genetic alterations related to the tuberous sclerosis complex (TSC) have been demonstrated. Striking improvements in the understanding of the genetic basis of this autosomal dominant genetic disease are coupled to the understanding of the mechanisms that link the loss of TSC1 (9q34) or TSC2 (16p13.3) genes with the regulation of the Rheb/m-TOR/p70S6K pathway.", "In all these lesions, genetic alterations related to the tuberous sclerosis complex (TSC) have been demonstrated. Striking improvements in the understanding of the genetic basis of this autosomal dominant genetic disease are coupled to the understanding of the mechanisms that link the loss of TSC1 (9q34) or TSC2 (16p13." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/7546221", "http://www.ncbi.nlm.nih.gov/pubmed/15579029", "http://www.ncbi.nlm.nih.gov/pubmed/10823953", "http://www.ncbi.nlm.nih.gov/pubmed/20073603", "http://www.ncbi.nlm.nih.gov/pubmed/15565817", "http://www.ncbi.nlm.nih.gov/pubmed/11520734", "http://www.ncbi.nlm.nih.gov/pubmed/9743993", "http://www.ncbi.nlm.nih.gov/pubmed/24105488", "http://www.ncbi.nlm.nih.gov/pubmed/15563017" ]

[]

[ "http://www.disease-ontology.org/api/metadata/DOID:13515", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D014402" ]

[ "The ATP-dependent chromatin-remodelling enzyme Chd1 is a 168-kDa protein consisting of a double chromodomain, Snf2-related ATPase domain, and a C-terminal DNA-binding domain. One of the two chromodomains of Chd1 specifically interacts with the methylated lysine 4 mark on histone H3 that is associated with transcriptional activity. Human CHD1 is an ATP-dependent chromatin remodeling protein, as a factor that directly and selectively recognizes histone H3 methylated on lysine 4." ]

[ "Chd1 is an ATP-dependent DNA helicase" ]

[ "The DNA-binding domain of the Chd1 chromatin-remodelling enzyme contains SANT and SLIDE domains", "The ATP-dependent chromatin-remodelling enzyme Chd1 is a 168-kDa protein consisting of a double chromodomain, Snf2-related ATPase domain, and a C-terminal DNA-binding domain.", "The presence of these domains in ISWI and Chd1 chromatin-remodelling enzymes may provide a means of efficiently harnessing the action of the Snf2-related ATPase domain for the purpose of nucleosome spacing and provide an explanation for partial redundancy between these proteins.", "Here we identify the chromatin remodelling protein Chd1 (chromo-ATPase/helicase-DNA binding domain 1) as a component of SAGA and SLIK", "one of the two chromodomains of Chd1 specifically interacts with the methylated lysine 4 mark on histone H3 that is associated with transcriptional activity", "Human but not yeast CHD1 binds directly and selectively to histone H3 methylated at lysine 4 via its tandem chromodomains", "In the current study, we identify human CHD1, an ATP-dependent chromatin remodeling protein, as a factor that directly and selectively recognizes histone H3 methylated on lysine 4", "human CHD1 binds to methylated H3K4 in a manner that requires both of its tandem chromodomains.", "Our findings indicate that yeast and human CHD1 have diverged in their ability to discriminate covalently modified histones and link histone modification-recognition and non-covalent chromatin remodeling activities within a single human protein.", "We find that the yeast Isw1a, Isw2, and Chd1 enzymes preferentially move nucleosomes toward more central locations on short DNA fragments whereas Isw1b does not. ", "Analysis of nucleosome repositioning by yeast ISWI and Chd1 chromatin remodeling complexes.", "However, a key difference is that the Isw1a, Isw2, and Chd1 enzymes are unable to move nucleosomes to positions closer than 15 bp from a DNA end, whereas Isw1b can.", "The ISWI and CHD1 chromatin remodelling activities influence ADH2 expression and chromatin organization", "Here we show that the absence of the Isw1 and Chd1 ATP-dependent chromatin remodelling activities delays the maximal expression of ADH2 without impairing the chromatin remodelling that occurs upon activation.", "Thus, the ISWI and Chd1 remodelling factors are not only involved in transcription-related chromatin remodelling, but also are required to maintain a specific chromatin configuration across the yeast genome.", "the lack of Chd1 combined with the absence of Isw1 and Isw2 impairs nucleosome spacing along the ADH2 gene, and genome-wide in S. cerevisiae", "Through inclusion of Chd1 sequences in homology searches SLIDE domains were identified in CHD6-9 proteins. ", "The molecular motor protein CHD1 has been implicated in the regulation of transcription and in the transcription-independent genome-wide incorporation of H3.3 into paternal chromatin in Drosophila melanogaster.", "Interestingly, changes in CHD1 protein levels did not correlate with changes in the levels of the euchromatin mark H3K4me3 or elongating RNA Polymerase II.", "CHD1 is known to bind H3K4me3 in mammalian cells, and Neurospora CHD1 is required for proper regulation of the frequency (frq) gene.", "The molecular motor protein CHD1 has been implicated in the regulation of transcription and in the transcription-independent genome-wide incorporation of H3.3 into paternal chromatin in Drosophila melanogaster. ", "Thus, while CHD1 is localized to transcriptionally active regions of the genome, it can function to alter the levels of HP1a, perhaps through changes in methylation of H3K9.", "Histone H3K4 and K36 methylation, Chd1 and Rpd3S oppose the functions of Saccharomyces cerevisiae Spt4-Spt5 in transcription.", "Interestingly, changes in CHD1 protein levels did not correlate with changes in the levels of the euchromatin mark H3K4me3 or elongating RNA Polymerase II.", "The molecular motor protein CHD1 has been implicated in the regulation of transcription and in the transcription-independent genome-wide incorporation of H3.3 into paternal chromatin in Drosophila melanogaster.", "Interestingly, changes in CHD1 protein levels did not correlate with changes in the levels of the euchromatin mark H3K4me3 or elongating RNA Polymerase II. Thus, while CHD1 is localized to transcriptionally active regions of the genome, it can function to alter the levels of HP1a, perhaps through changes in methylation of H3K9.", " Chromodomain from heterochromatin protein 1 and polycomb protein is known to be a lysine-methylated histone H3 tail-binding module. Chromo-helicase/ATPase DNA-binding protein 1 (CHD1) is an ATP-dependent chromatin remodeling factor, containing two tandem chromodomains.", "Over-expression of an ATPase inactive form of CHD1 did not result in severe chromosomal defects, suggesting that the ATPase activity is required for this in vivo phenotype. Interestingly, changes in CHD1 protein levels did not correlate with changes in the levels of the euchromatin mark H3K4me3 or elongating RNA Polymerase II.", "Interestingly, changes in CHD1 protein levels did not correlate with changes in the levels of the euchromatin mark H3K4me3 or elongating RNA Polymerase II." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/16263726", "http://www.ncbi.nlm.nih.gov/pubmed/16468993", "http://www.ncbi.nlm.nih.gov/pubmed/17098252", "http://www.ncbi.nlm.nih.gov/pubmed/21177652", "http://www.ncbi.nlm.nih.gov/pubmed/23533627", "http://www.ncbi.nlm.nih.gov/pubmed/21623345", "http://www.ncbi.nlm.nih.gov/pubmed/15647753", "http://www.ncbi.nlm.nih.gov/pubmed/23319591", "http://www.ncbi.nlm.nih.gov/pubmed/16606615", "http://www.ncbi.nlm.nih.gov/pubmed/19948887" ]

[]

[ "http://www.uniprot.org/uniprot/CHD1_MOUSE", "http://www.uniprot.org/uniprot/CHD1_DROME" ]

[ "Fluorouracil, epirubicin, and cyclophosphamide are included in the FEC-75 regimen. This chemotherapy regiment is used for breast cancer treatment." ]

[ "fluorouracil", "epirubicin", "cyclophosphamide" ]

[ "Fluorouracil, epirubicin, and cyclophosphamide (FEC-75) followed by paclitaxel plus trastuzumab versus paclitaxel plus trastuzumab followed by FEC-75 plus trastuzumab as neoadjuvant treatment for patients with HER2-positive breast cancer (Z1041): a randomised, controlled, phase 3 trial.", "Patients randomly assigned to sequential treatment received fluorouracil 500 mg/m(2), epirubicin 75 mg/m(2), and cyclophosphamide 500 mg/m(2) (FEC-75) on day 1 of a 21-day cycle for four cycles followed by paclitaxel 80 mg/m(2) and trastuzumab 2 mg/kg (after a 4 mg/kg loading dose) once per week for 12 weeks, while those randomly assigned to the concurrent treatment group received paclitaxel and trastuzumab once per week for 12 weeks followed by four cycles of FEC-75 (on day 1 of each 21-day cycle) and once-weekly trastuzumab, in the same doses as the sequential group.", "In May 2008, the patient underwent preoperative chemotherapy consisting of 4 courses of FEC 75(fluororracil, epirubicin, and cyclophosphamide).", "Stage II-IIIC HER2-positive breast cancer patients, including inflammatory disease, were treated with weekly-trastuzumab for 24 weeks administered concurrently with all primary chemotherapy containing paclitaxel (80 mg/m(2)) for 12 weeks and 4 cycles of FEC-75 (fluorouracil 500 mg/m(2), epirubicine 75 mg/m(2), and cyclophosphamide 500 mg/m(2)) followed by surgery. ", "Further improvements can be achieved with dose-dense regimens, but densification of fluorouracil/epirubicin/cyclophosphamide (FEC) has proved difficult, with FEC(60) providing little benefit over standard chemotherapy and FEC(100) associated with toxicity. We investigated the feasibility of two intermediate dose-dense FEC regimens. Patients were randomised to six cycles of FEC(75) or FEC(90), with all three drugs given on day 1 of each 14-day cycle. ", "BACKGROUND: A previously published prospective randomized phase 3 trial showed that administration of 24 weeks of primary systemic chemotherapy (PST) with paclitaxel and FEC(75) (fluorouracil, epirubicin, cyclophosphamide) concurrently with trastuzumab in patients with HER2-positive primary breast cancer resulted in a 60% pathologic complete response rate (PCR) with no associated severe cardiac toxicity. ", "Maintenance chemotherapy was FEC 75 (fluorouracil 500 mg/m(2), epirubicin 75 mg/m(2), and cyclophosphamide 500 mg/m(2) on Day 1 every 21 days for 4 cycles). ", "The French Epirubicin Study Group carried out a randomized trial comparing epirubicin alone 75 mg/m2 with fluorouracil (5FU) 500 mg/m2, cyclophosphamide 500 mg/m2, and epirubicin 50 mg/m2 (FEC 50) and 5FU 500 mg/m2, cyclophosphamide 500 mg/m2, and epirubicin 75 mg/m2 (FEC 75) as first treatment for advanced breast cancer patients.", "Patients were randomised to 1 of 3 treatment groups: Group A (n = 207) received FEC 50 (fluorouracil 500 mg/m2, epirubicin 50 mg/m2 plus cyclophosphamide 500 mg/m2) every 21 days for 6 cycles; Group B (n = 193) received FEC 50 every 21 days for 3 cycles; Group C (n = 195) received FEC 75 (fluorouracil 500 mg/m2, epirubicin 75 mg/m2 plus cyclophosphamide 500 mg/m2) every 21 days for 3 cycles.", "Sixty chemotherapy-naive breast cancer patients of 30 to 71 years in age, P.S. = 0-1, receiving 5-fluorouracil-epirubicin-cyclophosphamide (FEC 75) q 21 days or cyclophosphamide-methotrexate-5-fluorouracil (CMF) or 120 mg/m2 epirubicin or high dose mitomycin-methotrexate-mitoxantrone (MMM) q 14 days (+ G-CSF) or 100 mg/m2 epirubicin (+ G-CSF) were randomized to receive, 15 min before chemotherapy, 8 mg i.v. bolus of ondansetron or 3 mg i.v. granisetron or 5 mg i.v. tropisetron and no further antiemetic therapy in the following days.", "PATIENTS AND METHODS: Four hundred seventeen anthracycline-naive MBC patients were randomized to receive one of the following regimens: arm A: 11 cycles of fluorouracil 500 mg/m(2), epirubicin 75 mg/m(2), and cyclophosphamide 500 mg/m(2) (FEC 75) every 21 days; arm B: four cycles of FEC 100 (same regimen but with epirubicin 100 mg/m(2)) then eight cycles of FEC 50 (epirubicin 50 mg/m(2)); and arm C: four cycles of FEC 100 then restart the same regimen at disease progression in case of prior response or stabilization.", "The aim of this study, using a Fleming single-stage design, was to explore the efficacy and safety of Taxotere 100 x mg x m(-2) docetaxel and FEC 75 cyclophosphamide 500 mg x m(-2), fluorouracil 500 x mg x m(-2) and epirubicin 75 mg x m(-2), in alternating and sequential schedules for the first-line treatment of metastatic breast cancer.", "PATIENTS AND METHODS: Between 1986 and 1990, 621 patients with operable breast cancer were randomly assigned to receive fluorouracil (Roche SA, Basel, Switzerland) 500 mg/m2, epirubicin (Pharmacia SA, Milan, Italy) 50 mg/m2, and cyclophosphamide (Asta Medica AG, Frankfurt, Germany) 500 mg/m2 every 21 days (FEC 50) for six cycles (6 FEC 50); FEC 50 for three cycles (3 FEC 50); or the same regimen with epirubicin 75 mg/m2 (FEC 75) for three cycles (3 FEC 75).", "We studied the feasibility of FEC (75) (fluorouracil: 500 mg/m(2), epirubicin: 75 mg/m(2), and cyclophosphamide:500 mg/m(2), q 3 w, 6 cycles) as adjuvant chemotherapy for 59 primary breast cancer patients.", "Between 1986 and 1990, 621 patients with operable breast cancer were randomly assigned to receive fluorouracil (Roche SA, Basel, Switzerland) 500 mg/m2, epirubicin (Pharmacia SA, Milan, Italy) 50 mg/m2, and cyclophosphamide (Asta Medica AG, Frankfurt, Germany) 500 mg/m2 every 21 days (FEC 50) for six cycles (6 FEC 50); FEC 50 for three cycles (3 FEC 50); or the same regimen with epirubicin 75 mg/m2 (FEC 75) for three cycles (3 FEC 75)", "Four hundred seventeen anthracycline-naive MBC patients were randomized to receive one of the following regimens: arm A: 11 cycles of fluorouracil 500 mg/m(2), epirubicin 75 mg/m(2), and cyclophosphamide 500 mg/m(2) (FEC 75) every 21 days; arm B: four cycles of FEC 100 (same regimen but with epirubicin 100 mg/m(2)) then eight cycles of FEC 50 (epirubicin 50 mg/m(2)); and arm C: four cycles of FEC 100 then restart the same regimen at disease progression in case of prior response or stabilization.", "The French Epirubicin Study Group carried out a randomized trial comparing epirubicin alone 75 mg/m2 with fluorouracil (5FU) 500 mg/m2, cyclophosphamide 500 mg/m2, and epirubicin 50 mg/m2 (FEC 50) and 5FU 500 mg/m2, cyclophosphamide 500 mg/m2, and epirubicin 75 mg/m2 (FEC 75) as first treatment for advanced breast cancer patients" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/12525522", "http://www.ncbi.nlm.nih.gov/pubmed/16315865", "http://www.ncbi.nlm.nih.gov/pubmed/16282727", "http://www.ncbi.nlm.nih.gov/pubmed/18344024", "http://www.ncbi.nlm.nih.gov/pubmed/1988577", "http://www.ncbi.nlm.nih.gov/pubmed/10885599", "http://www.ncbi.nlm.nih.gov/pubmed/22902450", "http://www.ncbi.nlm.nih.gov/pubmed/11875727", "http://www.ncbi.nlm.nih.gov/pubmed/18189160", "http://www.ncbi.nlm.nih.gov/pubmed/24239210", "http://www.ncbi.nlm.nih.gov/pubmed/22772380", "http://www.ncbi.nlm.nih.gov/pubmed/7693420", "http://www.ncbi.nlm.nih.gov/pubmed/17647266", "http://www.ncbi.nlm.nih.gov/pubmed/17054108", "http://www.ncbi.nlm.nih.gov/pubmed/10963640", "http://www.ncbi.nlm.nih.gov/pubmed/8808724" ]

[]

[]

[ "The recurrent translocation breakpoint on chromosome 22 of neuroepithelioma has been localized between two probes, D22S1 and D22S15, by both in situ hybridization and somatic cell hybrids", "The recurrent translocation breakpoint on chromosome 22 of neuroepithelioma has been localized between two probes, D22S1 and D22S15, by both in situ hybridization and somatic cell hybrids. ", "The recurrent translocation breakpoint on chromosome 22 of neuroepithelioma has been localized between two probes, D22S1 and D22S15, by both in situ hybridization and somatic cell hybrids.", "The recurrent translocation breakpoint on chromosome 22 of neuroepithelioma has been localized between two probes, D22S1 and D22S15, by both in situ hybridization and somatic cell hybrids " ]

[ "D22S1", "D22S15" ]

[ "The recurrent translocation breakpoint on chromosome 22 of neuroepithelioma has been localized between two probes, D22S1 and D22S15, by both in situ hybridization and somatic cell hybrids", "The recurrent translocation breakpoint on chromosome 22 of neuroepithelioma has been localized between two probes, D22S1 and D22S15, by both in situ hybridization and somatic cell hybrids." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/2303258" ]

[]

[ "http://www.disease-ontology.org/api/metadata/DOID:4389", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D014178", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D015342", "http://www.disease-ontology.org/api/metadata/DOID:4388", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D056905" ]

[ "Perioperative administration of synthetic thyroid hormone therapy have positive hemodynamic effects (consisting of increases cardiac output, lowered systemic vascular resistance) determining improved postoperative ventricular function, reduced the need for treatment with inotropic agents and mechanical devices, in the absence of relevant effects on outcome ad exception of lower incidence of atrial fibrillation." ]

[ "no" ]

[ "Serum T3 concentrations were significantly higher with fewer patients having T3 concentrations below the normal range in the T3 group than the placebo group throughout the postoperative period. Hemodynamic variables, postoperative inotrope requirement, and outcome variables showed no differences between the groups", "We conclude that although widespread interest has been shown on the use of thyroid hormones in the perioperative period, and the effect of cardiopulmonary bypass on thyroid hormone metabolism widely studied, there is no substantial evidence to justify routine use of thyroid hormones in patients undergoing coronary artery bypass grafting.", "Treatment with GIK, T3, and GIK/T3 improves hemodynamic performance and results in reduced cTnI release in patients undergoing on-pump CABG surgery.", "Perioperative administration of triiodothyronine increased cardiac output slightly and decreased systemic vascular resistance, but it had no effect on operative outcome.", "Parenteral triiodothyronine given after crossclamp removal during elective coronary artery bypass grafting significantly improved postoperative ventricular function, reduced the need for treatment with inotropic agents and mechanical devices, and decreased the incidence of myocardial ischemia. The incidence of atrial fibrillation was slightly decreased, and the need for postoperative pacemaker support was reduced.", "Perioperative T3 administration decreased the incidence and need for treatment of postoperative atrial fibrillation.", " Intravenous T(3) does not have dramatic effects on hemodynamic variables in this setting as has been previously suggested. ", "Raising serum triiodothyronine concentrations in patients undergoing coronary-artery bypass surgery increases cardiac output and lowers systemic vascular resistance, but does not change outcome or alter the need for standard postoperative therapy.", "No significant differences were noted in the pre and post CPB hemodynamics between the two groups for the most part of the study except that heart rate was increased in T3 group.", "The haemodynamic parameters were no different between the two groups at any postoperative time point. Likewise, density and affinity of lymphocyte beta-adrenoceptors were not significantly different from pre-operative values in either group." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/18290900", "http://www.ncbi.nlm.nih.gov/pubmed/16820580", "http://www.ncbi.nlm.nih.gov/pubmed/19303793", "http://www.ncbi.nlm.nih.gov/pubmed/8633935", "http://www.ncbi.nlm.nih.gov/pubmed/19609889", "http://www.ncbi.nlm.nih.gov/pubmed/7995828", "http://www.ncbi.nlm.nih.gov/pubmed/12213743", "http://www.ncbi.nlm.nih.gov/pubmed/10343261", "http://www.ncbi.nlm.nih.gov/pubmed/7477166", "http://www.ncbi.nlm.nih.gov/pubmed/23958074", "http://www.ncbi.nlm.nih.gov/pubmed/8389710", "http://www.ncbi.nlm.nih.gov/pubmed/8594265" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D047549", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013963", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D020249", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001026", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D003324", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016896", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D014284", "http://www.biosemantics.org/jochem#4275387", "http://www.disease-ontology.org/api/metadata/DOID:3393" ]

[ "Computational methods attempting to identify instances of cis-regulatory modules (CRMs) in the genome face a challenging problem of searching for potentially interacting transcription factor binding sites while knowledge of the specific interactions involved remains limited. When discriminating CRMs from non-coding regions, those methods considering evolutionary conservation have a stronger predictive power than methods designed to be run on a single genome. Furthermore, most methods appear to be sensitive to the composition and structure of the genome to which they are applied. CisMiner allows to perform a blind search of CRMs without any prior information about target CRMs nor limitation in the number of motifs.", "The optimal choice of method varies depending on species and composition of the sequences in question. When discriminating CRMs from non-coding regions, those methods considering evolutionary conservation have a stronger predictive power than methods designed to be run on a single genome. Different CRM representations and search strategies rely on different CRM properties, and different methods can complement one another. For example, some favour homotypical clusters of binding sites, while others perform best on short CRMs. Furthermore, most methods appear to be sensitive to the composition and structure of the genome to which they are applied. A statistical model to describe the underlying cluster structure as well as individual motif conservation has also been proposed, accompanied with a Monte Carlo motif screening strategy for predicting novel regulatory modules in upstream sequences of coregulated genes." ]

[ "motif conservation", "fuzzy itemset mining", "combinatorial methods" ]

[ "Several tools allow to detect significant co-occurrences of closely located binding sites (cis-regulatory modules, CRMs). However, these tools present at least one of the following limitations: 1) scope limited to promoter or conserved regions of the genome; 2) do not allow to identify combinations involving more than two motifs; 3) require prior information about target motifs.", "In this work we present CisMiner, a novel methodology to detect putative CRMs by means of a fuzzy itemset mining approach able to operate at genome-wide scale. CisMiner allows to perform a blind search of CRMs without any prior information about target CRMs nor limitation in the number of motifs. CisMiner tackles the combinatorial complexity of genome-wide cis-regulatory module extraction using a natural representation of motif combinations as itemsets and applying the Top-Down Fuzzy Frequent- Pattern Tree algorithm to identify significant itemsets.", "To be able to handle the large datasets, the query-based setting and other specificities proper to CRM detection on ChIP-Seq based data, we developed a novel powerful CRM detection method 'CPModule'", "the optimal choice of method varies depending on species and composition of the sequences in question. When discriminating CRMs from non-coding regions, those methods considering evolutionary conservation have a stronger predictive power than methods designed to be run on a single genome. Different CRM representations and search strategies rely on different CRM properties, and different methods can complement one another. For example, some favour homotypical clusters of binding sites, while others perform best on short CRMs. Furthermore, most methods appear to be sensitive to the composition and structure of the genome to which they are applied. ", "CisMiner: genome-wide in-silico cis-regulatory module prediction by fuzzy itemset mining", "Additionally, we make a number of new predictions on combinatorial regulation of these five key TFs with other TFs documented in TRANSFAC.", "Due to degeneracy of nucleotide content among binding site instances or motifs, and intricate 'grammatical organization' of motifs within cis-regulatory modules (CRMs), extant pattern matching-based in silico motif search methods often suffer from impractically high false positive rates, especially in the context of analyzing large genomic datasets, and noisy position weight matrices which characterize binding sites", "Genome-wide identification of cis-regulatory motifs and modules underlying gene coregulation using statistics and phylogeny.", "We thus developed a new CRM identification method MOPAT (motif pair tree), which identifies CRMs through the identification of motif modules, groups of motifs co-occurring in multiple CRMs. It can identify 'orthologous' CRMs without multiple alignments.", "These methods are problematic when binding sites are not well aligned in multiple alignments or when the number of input known motifs is large. We thus developed a new CRM identification method MOPAT (motif pair tree), which identifies CRMs through the identification of motif modules, groups of motifs co-occurring in multiple CRMs.", "We thus developed a new CRM identification method MOPAT (motif pair tree), which identifies CRMs through the identification of motif modules, groups of motifs co-occurring in multiple CRMs." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/22422841", "http://www.ncbi.nlm.nih.gov/pubmed/25268582", "http://www.ncbi.nlm.nih.gov/pubmed/15883375", "http://www.ncbi.nlm.nih.gov/pubmed/18606616", "http://www.ncbi.nlm.nih.gov/pubmed/20671200", "http://www.ncbi.nlm.nih.gov/pubmed/19478006", "http://www.ncbi.nlm.nih.gov/pubmed/21152003" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D008722", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D019295" ]

[ "MLN4924 is an investigational small molecule inhibitor of NEDD8-activating enzyme (NAE)." ]

[ "NEDD8-activating enzyme" ]

[ "Finally, MLN4924, an investigational small molecule inhibitor of NEDD8-activating enzyme (NAE) that inhibits CRL, suppresses in vitro migration, proliferation and tube formation, as well as in vivo angiogenesis and tumorigenesis. ", "MLN4924, a small molecule inhibitor of NEDD8 activating enzyme (NAE), has been reported to elicit an anti-tumor effect on various malignancies. ", "The more targeted impact of NEDD8-activating enzyme on protein degradation prompted us to study MLN4924, an investigational NEDD8-activating enzyme inhibitor, in preclinical multiple myeloma models.", "A gatekeeper residue for NEDD8-activating enzyme inhibition by MLN4924.", "Treatment-emergent mutations in NAEβ confer resistance to the NEDD8-activating enzyme inhibitor MLN4924.", "Quantifiable analysis of cellular pathway inhibition of a Nedd8-activating enzyme inhibitor, MLN4924, using AlphaScreen.", "Cellular effects of a Nedd8-activating enzyme (NAE) inhibitor, MLN4924, using the AlphaScreen format were explored.", "Quantitative proteomic analysis of cellular protein modulation upon inhibition of the NEDD8-activating enzyme by MLN4924.", "Inactivation of the Cullin (CUL)-RING E3 ligase by the NEDD8-activating enzyme inhibitor MLN4924 triggers protective autophagy in cancer cells.", "The Nedd8-activating enzyme inhibitor MLN4924 thwarts microenvironment-driven NF-κB activation and induces apoptosis in chronic lymphocytic leukemia B cells.", "Inhibition of Nedd8-activating enzyme by MLN4924 prevents the conjugation of cullin proteins with NEDD8, resulting in inactivation of the entire family of CRLs.", "Substrate-assisted inhibition of ubiquitin-like protein-activating enzymes: the NEDD8 E1 inhibitor MLN4924 forms a NEDD8-AMP mimetic in situ.", "To inhibit cellular neddylation, we used a cell line with tetracycline-inducible expression of a dominant-negative form of the Nedd8 E2 enzyme or treatment of cells with the Nedd8 E1 inhibitor MLN4924", "MLN4924 is a first-in-class experimental cancer drug that inhibits the NEDD8-activating enzyme, thereby inhibiting cullin-RING E3 ubiquitin ligases and stabilizing many cullin substrates", "MLN4924 is a first-in-class cancer drug that inhibits the Nedd8-activating enzyme (NAE)", "MLN4924 is an investigational agent that inhibits the Nedd8-activating enzyme, thereby neutralizing Cullin-RING ubiquitin ligases and preventing degradation of their substrates", "We used MLN4924, a phase 2 oncology therapeutic, which targets and inhibits the NEDD8-activating enzyme pathway involved in the ubiquitin-proteasome system", "Neddylation occurs through a multistep enzymatic process involving Nedd8 activating enzymes, and recent studies have shown that the pharmacological agent, MLN4924, can potently inhibit Nedd8 activating enzymes, thereby preventing neddylation of Cullin proteins and preventing the degradation of CRL target proteins", "The stability of the NEDD8-MLN4924 adduct within the NAE active site blocks enzyme activity, thereby accounting for the potent inhibition of the NEDD8 pathway by MLN4924. ", "MLN4924 is a first-in-class experimental cancer drug that inhibits the NEDD8-activating enzyme, thereby inhibiting cullin-RING E3 ubiquitin ligases and stabilizing many cullin substrates. ", "The NEDD8-activating enzyme inhibitor, MLN4924, cooperates with TRAIL to augment apoptosis through facilitating c-FLIP degradation in head and neck cancer cells.", "Initial testing of the investigational NEDD8-activating enzyme inhibitor MLN4924 by the pediatric preclinical testing program.", "MLN4924, a NEDD8-activating enzyme inhibitor, is active in diffuse large B-cell lymphoma models: rationale for treatment of NF-{kappa}B-dependent lymphoma.", " MLN4924 is a first-in-class cancer drug that inhibits the Nedd8-activating enzyme (NAE). Herein, we report that MLN4924 inhibits Vpx/Vpr-induced SAMHD1 degradation by inhibiting the neddylation of E3 ubiquitin ligase and blocks macaque simian immunodeficiency virus (SIVmac) replication in myeloid cells.", "Neddylation can be prevented by MLN4924, a drug that inhibits the nedd8-activating enzyme. We report that MLN4924 inhibits the neddylation of CRL4, blocking Vpx-induced degradation of SAMHD1 and maintaining the restriction.", " MLN4924 is a first-in-class experimental cancer drug that inhibits the NEDD8-activating enzyme, thereby inhibiting cullin-RING E3 ubiquitin ligases and stabilizing many cullin substrates. The mechanism by which MLN4924 inhibits cancer cell proliferation has not been defined, although it is accompanied by DNA rereplication and attendant DNA damage.", "MLN4924 inhibits NAE (NEDD8 Activating Enzyme),", " MLN4924 is an investigational small-molecule inhibitor of NEDD8-activating enzyme (NAE) in clinical trials for the treatment of cancer. MLN4924 is a mechanism-based inhibitor, with enzyme inhibition occurring through the formation of a tight-binding NEDD8-MLN4924 adduct.", "Ubiquitin-activating enzyme (UAE or E1) activates ubiquitin via an adenylate intermediate and catalyzes its transfer to a ubiquitin-conjugating enzyme (E2). MLN4924 is an adenosine sulfamate analogue that was identified as a selective, mechanism-based inhibitor of NEDD8-activating enzyme (NAE), another E1 enzyme, by forming a NEDD8-MLN4924 adduct that tightly binds at the active site of NAE, a novel mechanism termed substrate-assisted inhibition (Brownell, J.", "(2010) elucidate the mechanism of action of MLN4924, a NEDD8-activating enzyme inhibitor. MLN4924 requires the activity of the enzyme to generate a NEDD8-adenylate analog that potently and selectively shuts down this posttranslational modification system.", " Cellular effects of a Nedd8-activating enzyme (NAE) inhibitor, MLN4924, using the AlphaScreen format were explored. MLN4924 acts as a substrate-assisted inhibitor of NAE by forming a tight binding Nedd8-MLN4924 adduct.", "MLN4924 is a first-in-class cancer drug that inhibits the Nedd8-activating enzyme (NAE). Herein, we report that MLN4924 inhibits Vpx/Vpr-induced SAMHD1 degradation by inhibiting the neddylation of E3 ubiquitin ligase and blocks macaque simian immunodeficiency virus (SIVmac) replication in myeloid cells.", "MLN4924 is a first-in-class experimental cancer drug that inhibits the NEDD8-activating enzyme, thereby inhibiting cullin-RING E3 ubiquitin ligases and stabilizing many cullin substrates. The mechanism by which MLN4924 inhibits cancer cell proliferation has not been defined, although it is accompanied by DNA rereplication and attendant DNA damage.", "MLN4924 is an investigational small-molecule inhibitor of NEDD8-activating enzyme (NAE) in clinical trials for the treatment of cancer. MLN4924 is a mechanism-based inhibitor, with enzyme inhibition occurring through the formation of a tight-binding NEDD8-MLN4924 adduct.", "Cellular effects of a Nedd8-activating enzyme (NAE) inhibitor, MLN4924, using the AlphaScreen format were explored. MLN4924 acts as a substrate-assisted inhibitor of NAE by forming a tight binding Nedd8-MLN4924 adduct." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/22874562", "http://www.ncbi.nlm.nih.gov/pubmed/19360080", "http://www.ncbi.nlm.nih.gov/pubmed/24672057", "http://www.ncbi.nlm.nih.gov/pubmed/20142034", "http://www.ncbi.nlm.nih.gov/pubmed/21873567", "http://www.ncbi.nlm.nih.gov/pubmed/21969368", "http://www.ncbi.nlm.nih.gov/pubmed/24213570", "http://www.ncbi.nlm.nih.gov/pubmed/21677879", "http://www.ncbi.nlm.nih.gov/pubmed/25615422", "http://www.ncbi.nlm.nih.gov/pubmed/24634471", "http://www.ncbi.nlm.nih.gov/pubmed/21914854", "http://www.ncbi.nlm.nih.gov/pubmed/24525735", "http://www.ncbi.nlm.nih.gov/pubmed/22951983", "http://www.ncbi.nlm.nih.gov/pubmed/21994410", "http://www.ncbi.nlm.nih.gov/pubmed/22439935", "http://www.ncbi.nlm.nih.gov/pubmed/22012946", "http://www.ncbi.nlm.nih.gov/pubmed/22246439", "http://www.ncbi.nlm.nih.gov/pubmed/22832224", "http://www.ncbi.nlm.nih.gov/pubmed/21417215", "http://www.ncbi.nlm.nih.gov/pubmed/22927439", "http://www.ncbi.nlm.nih.gov/pubmed/21159650", "http://www.ncbi.nlm.nih.gov/pubmed/20129059", "http://www.ncbi.nlm.nih.gov/pubmed/24155378", "http://www.ncbi.nlm.nih.gov/pubmed/22072567", "http://www.ncbi.nlm.nih.gov/pubmed/21463634", "http://www.ncbi.nlm.nih.gov/pubmed/20525923", "http://www.ncbi.nlm.nih.gov/pubmed/23624319", "http://www.ncbi.nlm.nih.gov/pubmed/25388161", "http://www.ncbi.nlm.nih.gov/pubmed/23527154", "http://www.ncbi.nlm.nih.gov/pubmed/23986575" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004791" ]

[ "Phospholamban interacts with HAX-1, a mitochondrial protein with anti-apoptotic function.The discovery of the PLN/HAX-1 interaction therefore unveils an important new link between Ca(2+) homeostasis and cell survival, with significant therapeutic potential.", "The HS-1 associated protein X-1 (HAX-1) is a mitochondrial protein with anti-apoptotic function and presents with numerous similarities to Bcl-2. and was identified as a phospholamban-binding partner. Using the yeast-two-hybrid system, HS-1 associated protein X-1 (HAX-1) was identified as a PLN-binding partner.", "The sarco(endo)plasmic reticulum (SR) Ca(2+) transport ATPase (SERCA2a) and its inhibitor phospholamban (PLN) control the uptake of Ca(2+) by SR membranes during relaxation. Recently, the antiapoptotic HS-1-associated protein X-1 (HAX-1) was identified as a binding partner of PLN, and this interaction was postulated to regulate cell apoptosis.Phospholamban interacts with HAX-1, a mitochondrial protein with anti-apoptotic function." ]

[ "The HS-1 associated protein X-1", "(HAX-1)" ]

[ "To identify additional proteins that may interact with PLN, we used the yeast-two-hybrid system to screen an adult human cardiac cDNA library. HS-1 associated protein X-1 (HAX-1) was identified as a PLN-binding partner.", "Analysis of the anti-apoptotic function of HAX-1 revealed that the presence of PLN enhanced the HAX-1 protective effects from hypoxia/reoxygenation-induced cell death. These findings suggest a possible link between the Ca(2+) handling by the sarcoplasmic reticulum and cell survival mediated by the PLN/HAX-1 interaction.", "The sarco(endo)plasmic reticulum Ca(2+) transport adenosine triphosphatase (SERCA2a) and its regulator phospholamban (PLN) have a central role in modulating Ca(2+) homeostasis and, therefore, cardiac function. Herein, we discuss the mechanisms through which SERCA2a and PLN control cardiomyocyte function in health and disease. Emphasis is placed on our newly identified PLN-binding partner HS-1-associated protein X-1 (HAX-1), which has an anti-apoptotic function and presents with numerous similarities to Bcl-2.", "The discovery of the PLN/HAX-1 interaction therefore unveils an important new link between Ca(2+) homeostasis and cell survival, with significant therapeutic potential.", "The sarco(endo)plasmic reticulum (SR) Ca(2+) transport ATPase (SERCA2a) and its inhibitor phospholamban (PLN) control the uptake of Ca(2+) by SR membranes during relaxation. Recently, the antiapoptotic HS-1-associated protein X-1 (HAX-1) was identified as a binding partner of PLN, and this interaction was postulated to regulate cell apoptosis.", "On triple transfections with PLN, however, HAX-1 massively translocated to the ER membranes, where it codistributed with PLN and SERCA2.", "These findings suggest that HAX-1 may promote cell survival through modulation of SERCA2 protein levels and thus ER Ca(2+) stores.", "Phospholamban interacts with HAX-1, a mitochondrial protein with anti-apoptotic function.", "The HS-1 associated protein X-1 (HAX-1) is a ubiquitously expressed protein that protects cardiomyocytes from programmed cell death. Here we identify HAX-1 as a regulator of contractility and calcium cycling in the heart. HAX-1 overexpression reduced sarcoplasmic reticulum Ca-ATPase (SERCA2) pump activity in isolated cardiomyocytes and in vivo, leading to depressed myocyte calcium kinetics and mechanics.", "The inhibitory effects of HAX-1 were abolished upon phosphorylation of phospholamban, which plays a fundamental role in controlling basal contractility and constitutes a key downstream effector of the beta-adrenergic signaling cascade.", " Furthermore, the effects of PLN and its phosphorylation on cardiac function are subject to additional regulation by its interacting partners, the anti-apoptotic HAX-1 protein and Gm or the anchoring unit of protein phosphatase 1.", " Emphasis is placed on our newly identified PLN-binding partner HS-1-associated protein X-1 (HAX-1), which has an anti-apoptotic function and presents with numerous similarities to Bcl-2.", "Furthermore, the effects of PLN and its phosphorylation on cardiac function are subject to additional regulation by its interacting partners, the anti-apoptotic HAX-1 protein and Gm or the anchoring unit of protein phosphatase 1" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/19920172", "http://www.ncbi.nlm.nih.gov/pubmed/18971376", "http://www.ncbi.nlm.nih.gov/pubmed/18415121", "http://www.ncbi.nlm.nih.gov/pubmed/17241641", "http://www.ncbi.nlm.nih.gov/pubmed/24550830" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D051017", "http://www.uniprot.org/uniprot/PPLA_RABIT", "http://www.uniprot.org/uniprot/PPLA_RAT", "http://www.uniprot.org/uniprot/PPLA_CHICK", "http://www.uniprot.org/uniprot/PPLA_MOUSE", "http://www.uniprot.org/uniprot/PPLA_BOVIN", "http://www.uniprot.org/uniprot/PPLA_CANFA", "http://www.uniprot.org/uniprot/PPLA_PIG" ]

[ "One of several causes of sudden cardiac death in athletes is long QT syndrome" ]

[ "yes" ]

[ "A diversity of cardiovascular disorders including hypertrophic cardiomyopathy, congenital coronary anomalies, arrhythmogenic right ventricular dysplasia, dilated cardiomyopathy, aortic rupture due to Marfan syndrome, myocarditis, valvular disease and electrical disorders (Wolff-Parkinson-White syndrome, long QT syndrome, Brugada syndrome), as well as commotio cordis represent the common causes of SCD in young athletes.", "Sudden cardiac death is the leading cause of mortality among young athletes with an incidence of 1-2 per 100,000 athletes per annum.", "The majority of cases are caused by an underlying structural cardiac abnormality, most commonly hypertrophic cardiomyopathy. More recently, the understanding of non-structural causes such as long QT syndrome and Brugada syndrome has grown and diagnostic criteria have been developed. ", "This review considers in particular the causes of death affecting athletes below 35 years of age. In this age group the largest proportion of deaths are caused by diseases with autosomal dominant inheritance such as hypertrophic cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy, long QT-syndrome, and Marfan's syndrome. ", "Knowledge of sudden cardiac death in young athletes is imperative for all physicians and allied health professionals. ", "In this article, we review several etiologies of sudden cardiac death, including hypertrophic cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy, Wolff-Parkinson-White syndrome, long QT syndrome, Brugada syndrome, and commotio cordis. ", "Sudden cardiac death (SCD) in young athletes is generally caused by inherited cardiac disorders.", "The genetic abnormalities most associated with SCD are hypertrophic cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy, long QT syndrome, Brugada syndrome, and catecholaminergic polymorphic ventricular tachycardia.", "The most common cause of sudden cardiac death in athletes is hypertrophic cardiomyopathy. Other reasons are congenital coronary artery anomalies, nivocarditis, dilatative cardiomyopathy, arrhythmogenic cardiomyopathy of the right ventricle, sarcoidosis, mitral valve prolapse, aortic valve stenosis, atherosclerosis, long QT syndrome, and blunt impact to the chest.", "The congenital long QT syndrome (LQTS) is caused by cardiac ion channel mutations, which predispose young individuals to sudden cardiac death often related to exercise. ", "A group of relatively uncommon but important genetic cardiovascular diseases (GCVDs) are associated with increased risk for sudden cardiac death during exercise, including hypertrophic cardiomyopathy, long-QT syndrome, Marfan syndrome, and arrhythmogenic right ventricular cardiomyopathy.", "Primary electrical disorders (such as the long QT syndrome) are rarely present in athletes but, so far, are a considerable reason for disqualification from sport activity. " ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/17853713", "http://www.ncbi.nlm.nih.gov/pubmed/22362900", "http://www.ncbi.nlm.nih.gov/pubmed/20675977", "http://www.ncbi.nlm.nih.gov/pubmed/22375212", "http://www.ncbi.nlm.nih.gov/pubmed/20089483", "http://www.ncbi.nlm.nih.gov/pubmed/17726868", "http://www.ncbi.nlm.nih.gov/pubmed/16672832", "http://www.ncbi.nlm.nih.gov/pubmed/15184297", "http://www.ncbi.nlm.nih.gov/pubmed/11475927", "http://www.ncbi.nlm.nih.gov/pubmed/24198575", "http://www.ncbi.nlm.nih.gov/pubmed/15074012", "http://www.ncbi.nlm.nih.gov/pubmed/19535269", "http://www.ncbi.nlm.nih.gov/pubmed/12831662", "http://www.ncbi.nlm.nih.gov/pubmed/21234187" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016757", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D008133", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D056352" ]

[ "MammaPrint has a prognostic value for distant metastasis and death, as well as predictive value for response to adjuvant chemotherapy in patients with breast cancer. However, the EGAPP Working Group found no evidence regarding the clinical utility of the MammaPrint." ]

[]

[ "In the intermediate-risk subgroup, the 70-gene signature could be useful to decide in elderly patients whether they may benefit from adjuvant chemotherapy or not.", "Adjuvant assessment tools for prognosis and prediction of treatment benefit, including Adjuvant! Online, the St Gallen Consensus, Oncotype DX(®) and MammaPrint(®), aid clinical decision making", "The 70-gene MammaPrint prognosis profile accurately identified Japanese breast cancer patients at low risk of developing recurrences. In fact, 100% of the individuals in the low-risk category remained metastasis-free for the duration of the observation period.", "he probability of distant metastasis-free survival at five years was 100% for the low-risk group and 94% for the high-risk group.", "The 70-gene prognosis signature can accurately select postmenopausal patients at low risk of breast cancer-related death within 5 years of diagnosis and can be of clinical use in selecting postmenopausal women for adjuvant chemotherapy.", "The 70-gene signature (MammaPrint) is a prognostic tool used to guide adjuvant treatment decisions", "A pCR is unlikely to be achieved in tumors that have a good prognosis-signature. Tumors with a poor prognosis-signature are more sensitive to chemotherapy.", "The EWG found adequate evidence to characterize the association of MammaPrint with future metastases, but inadequate evidence to assess the added value to standard risk stratification, and could not determine the population to which the test would best apply.", "he EWG found no evidence regarding the clinical utility of the MammaPrint and Quest H:I Ratio tests, and inadequate evidence regarding Oncotype DX. These technologies have potential for both benefit and harm", "MammaPrint, an oligonucleotide microassay performed on fresh-frozen tumor samples, analyzes the expression of 70 genes. Studies have found that MammaPrint allows young patients (<61 years) with early-stage breast cancer to be categorized as having a high or low risk of distant metastasis. High-risk patients may then be managed with more aggressive therapy." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/22553468", "http://www.ncbi.nlm.nih.gov/pubmed/20110242", "http://www.ncbi.nlm.nih.gov/pubmed/20975745", "http://www.ncbi.nlm.nih.gov/pubmed/19125125", "http://www.ncbi.nlm.nih.gov/pubmed/21847392", "http://www.ncbi.nlm.nih.gov/pubmed/18159035", "http://www.ncbi.nlm.nih.gov/pubmed/19825882", "http://www.ncbi.nlm.nih.gov/pubmed/19214742" ]

[ { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A7746488", "o": "Clinic" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A8316941", "o": "Clinical" } ]

[ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013677", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D003695", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D008495", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D015510", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D019411" ]

[ "M3/6 (DUSP8) is a dual-specificity phosphatase implicated in the dephosphorylation and inactivation of JNK and, to a lesser extent, p38 MAPKs.", "Yes. Phosphatases play a particularly important role in this respect, by tightly controlling MAPK phosphorylation and activation. M3/6 (DUSP8) is a dual-specificity phosphatase implicated in the dephosphorylation and inactivation of JNK and, to a lesser extent, p38 MAPKs and is found in a complex with these kinases, along with other pathway components, held together by scaffold proteins.", "The protein M3/6 (DUSP8) is a dual-specificity phosphatase implicated in the dephosphorylation and inactivation of JNK" ]

[ "yes" ]

[ "Involvement of the dual-specificity phosphatase M3/6 in c-Jun N-terminal kinase inactivation following cerebral ischemia in the rat hippocampus.", "The results revealed upregulation of dual-specificity phosphatase M3/6 (DUSP8) activity at 4 h of reperfusion in rat hippocampi. ", "This study examines the molecular mechanism underlying JNK dephosphorylation and inactivation evoked by dual-specificity phosphates following cerebral ischemia.", "Phosphatases play a particularly important role in this respect, by tightly controlling MAPK phosphorylation and activation. M3/6 (DUSP8) is a dual-specificity phosphatase implicated in the dephosphorylation and inactivation of JNK and, to a lesser extent, p38 MAPKs and is found in a complex with these kinases, along with other pathway components, held together by scaffold proteins. ", "Dual-specificity phosphatases (DUSPs) play a very important role in these events by modulating the extent of JNK phosphorylation and activation and thus regulating cellular responses to stress. M3/6 (DUSP8) is one of the dual-specificity protein phosphatases with distinct specificity towards JNK.", "M3/6 is a dual-specificity phosphatase selective for JNK [7, 8]. ", "Here we describe two new dual specificity phosphatases of the CL100/MKP-1 family that are selective for inactivating ERK or JNK/SAPK and p38 MAP kinases when expressed in COS-7 cells. M3/6 is the first phosphatase of this family to display highly specific inactivation of JNK/SAPK and p38 MAP kinases. ", "We previously demonstrated that the dual specificity phosphatases (DSPs) MKP7 and M3/6 bind the scaffold JNK-interacting protein-1 (JIP-1) and inactivate the bound subset of JNK (1).", "the dual-specificity phosphatase M3/6", " dual-specificity phosphatase M3/6 (DUSP8)", "M3/6 (DUSP8) is a dual-specificity phosphatase implicated in the dephosphorylation and inactivation of JNK ", "the M3/6 dual-specificity phosphatase", "M3/6 (DUSP8) is one of the dual-specificity protein phosphatases with distinct specificity towards JNK", "M3/6 is a dual-specificity phosphatase selective for JNK", "The dual specificity phosphatases M3/6 and MKP-3 are highly selective for inactivation of distinct mitogen-activated protein kinases.", "Phosphorylation of the M3/6 dual-specificity phosphatase enhances the activation of JNK by arsenite.", "Indeed, expanded polyglutamine impaired the solubility of the dual-specificity JNK phosphatase M3/6.", "Regulation of dual-specificity phosphatases M3/6 and hVH5 by phorbol esters.", "M3/6 (DUSP8) is one of the dual-specificity protein phosphatases with distinct specificity towards JNK.", "M3/6 is a dual-specificity phosphatase selective for JNK [7, 8]", "M3/6 (DUSP8) is one of the dual-specificity protein phosphatases with distinct specificity towards JNK", "Here we describe how diverse cellular stresses affect differently the stability and activity of a JNK-inactivating dual-specificity threonine-tyrosine phosphatase M3/6", "M3/6 is a dual-specificity phosphatase selective for JNK [7, 8]", "Regulation of dual-specificity phosphatases M3/6 and hVH5 by phorbol esters. Analysis of a delta-like domain.", "The results revealed upregulation of dual-specificity phosphatase M3/6 (DUSP8) activity at 4 h of reperfusion in rat hippocampi", "Indeed, expanded polyglutamine impaired the solubility of the dual-specificity JNK phosphatase M3/6", "Here we report that JIP-1 also binds the dual-specificity phosphatases MKP7 and M3/6 via a region independent of its JNK binding domain.", "Differential regulation of M3/6 (DUSP8) signaling" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/15888437", "http://www.ncbi.nlm.nih.gov/pubmed/11566103", "http://www.ncbi.nlm.nih.gov/pubmed/23679081", "http://www.ncbi.nlm.nih.gov/pubmed/22100391", "http://www.ncbi.nlm.nih.gov/pubmed/8910287", "http://www.ncbi.nlm.nih.gov/pubmed/11948422", "http://www.ncbi.nlm.nih.gov/pubmed/12524447", "http://www.ncbi.nlm.nih.gov/pubmed/12598532", "http://www.ncbi.nlm.nih.gov/pubmed/10915787", "http://www.ncbi.nlm.nih.gov/pubmed/23159405" ]

[]

[ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0016791", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D054638", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D054637", "http://www.uniprot.org/uniprot/DUS1_RAT", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0004712", "http://www.uniprot.org/uniprot/DUS8_MOUSE", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0008138", "http://www.uniprot.org/uniprot/DUS2_MOUSE", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D054641", "http://www.uniprot.org/uniprot/DUS3_HUMAN", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0017017", "http://www.uniprot.org/uniprot/DUS8_HUMAN" ]

[ "Biological databases are used to store and edit large amount of data, created from genomics data. In the most of the cases the data are stored according to their type but there are cases of focused databases that store database on a specific disease. In the case of renal disease there are plenty of databases, for example KUPKB a collection of omics datasets, Nephromine a renal genome-wide gene expression dataset based in transcriptomics, CDKD and Proteomics Database in Chronic Kidney Disease." ]

[ "yes" ]

[ "Proteomics database in chronic kidney disease", "Naturally occurring human urinary peptides for use in diagnosis of chronic kidney disease" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/20616184", "http://www.ncbi.nlm.nih.gov/pubmed/23593176", "http://www.ncbi.nlm.nih.gov/pubmed/19604367", "http://www.ncbi.nlm.nih.gov/pubmed/19703314", "http://www.ncbi.nlm.nih.gov/pubmed/21044771", "http://www.ncbi.nlm.nih.gov/pubmed/21930502", "http://www.ncbi.nlm.nih.gov/pubmed/21143788", "http://www.ncbi.nlm.nih.gov/pubmed/17877839" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D020869", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D059467", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D051436", "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=D015870" ]

[ "The most prevalent antibody numbering systems are the Kabat system, the Chothia system as well as the IMGT numbering system." ]

[]

[ "IMGT is a high quality integrated knowledge resource specialized in immunoglobulins (IG), T cell receptors (TR), major histocompatibility complex (MHC) of human and other vertebrates, and related proteins of the immune system (RPI) of any species which belong to the immunoglobulin superfamily (IgSF) and to the MHC superfamily (MhcSF). IMGT consists of five databases, ten on-line tools and more than 8,000 HTML pages of Web resources. IMGT provides a common access to standardized data from genome, genetics, proteome and three-dimensional structures. ", "amino acid positions according to the IMGT unique numbering (NUMEROTATION) that are used in IMGT/3Dstructure-DB cards, results of contact analysis and renumbered flat files.", "Standardized sequence and structure analysis of antibody using IMGT(®) databases and tools allows one to bridge, for the first time, the gap between antibody sequences and three-dimensional (3D) structures. This is achieved through the IMGT Scientific chart rules, based on the IMGT-ONTOLOGY concepts of classification (IMGT gene and allele nomenclature), description (IMGT standardized labels), and numerotation (IMGT unique numbering and IMGT Colliers de Perles). ", "Kabat Database was initially started in 1970 to determine the combining site of antibodies based on the available amino acid sequences at that time.", "comparative analysis of the main-chain conformation of the L1, L2, L3, H1 and H2 hypervariable regions in 17 immunoglobulin structures that have been accurately determined at high resolution is described. This involves 79 hypervariable regions in all. We also analysed a part of the H3 region in 12 of the 15 VH domains considered here. On the basis of the residues at key sites the 79 hypervariable regions can be assigned to one of 18 different canonical structures. We show that 71 of these hypervariable regions have a conformation that is very close to what can be defined as a \"standard\" conformation of each canonical structure. These standard conformations are described in detail. The other eight hypervariable regions have small deviations from the standard conformations that, in six cases, involve only the rotation of a single peptide group", "the basis of comparative studies of known antibody structures and sequences it has been argued that there is a small repertoire of main-chain conformations for at least five of the six hypervariable regions of antibodies, and that the particular conformation adopted is determined by a few key conserved residues." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/23157214", "http://www.ncbi.nlm.nih.gov/pubmed/22907343", "http://www.ncbi.nlm.nih.gov/pubmed/8227075", "http://www.ncbi.nlm.nih.gov/pubmed/22665257", "http://www.ncbi.nlm.nih.gov/pubmed/2687698", "http://www.ncbi.nlm.nih.gov/pubmed/12182069", "http://www.ncbi.nlm.nih.gov/pubmed/10592229", "http://www.ncbi.nlm.nih.gov/pubmed/19900967", "http://www.ncbi.nlm.nih.gov/pubmed/18503082", "http://www.ncbi.nlm.nih.gov/pubmed/16305737", "http://www.ncbi.nlm.nih.gov/pubmed/8918594", "http://www.ncbi.nlm.nih.gov/pubmed/9367782", "http://www.ncbi.nlm.nih.gov/pubmed/22390639" ]

[]

[ "http://www.biosemantics.org/jochem#4000002", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D007158", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D000906", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D007136", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0003823" ]

[ "Yes. The plant DOMAINS REARRANGED METHYLTRANSFERASE2 (DRM2) is a homolog of the mammalian de novo methyltransferase DNMT3. DRM2 contains a novel arrangement of the motifs required for DNA methyltransferase catalytic activity." ]

[ "yes" ]

[ "De novo DNA methylation in Arabidopsis thaliana is catalyzed by the methyltransferase DRM2, a homolog of the mammalian de novo methyltransferase DNMT3.", "Here we describe DNA methyltransferase genes from both Arabidopsis and maize that show a high level of sequence similarity to Dnmt3, suggesting that they encode plant de novo methyltransferases. Relative to all known eukaryotic methyltransferases, these plant proteins contain a novel arrangement of the motifs required for DNA methyltransferase catalytic activity. The N termini of these methyltransferases contain a series of ubiquitin-associated (UBA) domains. ", "BLASTX searches and phylogenetic analysis suggested that five cDNAs belonged to four classes (Dnmt1, Dnmt2, CMT and Dnmt3) of DNA methyltransferase genes." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/22058406", "http://www.ncbi.nlm.nih.gov/pubmed/11487702", "http://www.ncbi.nlm.nih.gov/pubmed/20505370", "http://www.ncbi.nlm.nih.gov/pubmed/15946751", "http://www.ncbi.nlm.nih.gov/pubmed/17660570", "http://www.ncbi.nlm.nih.gov/pubmed/11459824", "http://www.ncbi.nlm.nih.gov/pubmed/21150311", "http://www.ncbi.nlm.nih.gov/pubmed/23021223", "http://www.ncbi.nlm.nih.gov/pubmed/21060858", "http://www.ncbi.nlm.nih.gov/pubmed/15282033", "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", "http://www.ncbi.nlm.nih.gov/pubmed/10781108" ]

[]

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

[ "The number of protein coding genes in the human genome is currently estimated between 20,000 and 25,000" ]

[ "Between 20,000 and 25,000" ]

[ "Here, seven membrane protein topology prediction methods based on different underlying algorithms, such as hidden Markov models, neural networks and support vector machines, have been used for analysis of the protein sequences from the 21,416 annotated genes in the human genome.", "he GENCODE 7 release contains 20,687 protein-coding and 9640 long noncoding RNA loci and has 33,977 coding transcripts not represented in UCSC genes and RefSeq", "Current catalogs list a total of approximately 24,500 putative protein-coding genes.", "Clustering of these sequences using cross-species relationships suggests that millions of expressed sequences may correspond to only approximately 20,000 distinct protein-coding transcripts." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/18040051", "http://www.ncbi.nlm.nih.gov/pubmed/15034132", "http://www.ncbi.nlm.nih.gov/pubmed/20175080", "http://www.ncbi.nlm.nih.gov/pubmed/22955987" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016366", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011506", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005796" ]

[ "The rate of falls and the number of fallers was significantly reduced in two studies evaluating the effect of medication on preventing falls; one study (85 participants) compared vitamin D versus placebo in institutionalised women after stroke with low vitamin D levels, and the other study (79 participants) evaluated alendronate versus alphacalcidol in hospitalised people after stroke.\nTwo studies testing vitamin D versus placebo and alendronate versus alphacalcidol found a significant reduction in falls and the number of people falling.\nOverall, vitamin D did not reduce rate of falls (RaR 1.00, 95% CI 0.90 to 1.11; seven trials; 9324 participants) or risk of falling (RR 0.96, 95% CI 0.89 to 1.03; 13 trials; 26,747 participants), but may do so in people with lower vitamin D levels before treatment.\nWe found 26 eligible trials of moderate quality that enrolled 45,782 participants, the majority of which were elderly and female. Vitamin D use was associated with statistically significant reduction in the risk of falls (odds ratio for suffering at least one fall, 0.86; 95% confidence interval, 0.77-0.96)" ]

[ "yes" ]

[ "However, apart from the beneficial effects of 800 IU/d of vitamin D3 for reduction of falls in the elderly, causality remains yet unproven in randomized controlled trials (RCTs). ", "The rate of falls and the number of fallers was significantly reduced in two studies evaluating the effect of medication on preventing falls; one study (85 participants) compared vitamin D versus placebo in institutionalised women after stroke with low vitamin D levels, and the other study (79 participants) evaluated alendronate versus alphacalcidol in hospitalised people after stroke.", "Two studies testing vitamin D versus placebo and alendronate versus alphacalcidol found a significant reduction in falls and the number of people falling", ".Overall, vitamin D supplementation does not appear to reduce falls but may be effective in people who have lower vitamin D levels before treatment.", "Overall, vitamin D did not reduce rate of falls (RaR 1.00, 95% CI 0.90 to 1.11; seven trials; 9324 participants) or risk of falling (RR 0.96, 95% CI 0.89 to 1.03; 13 trials; 26,747 participants), but may do so in people with lower vitamin D levels before treatment.", "Vitamin D affects bone and muscle health and likely reduces the risk of falls in the elderly.", "We found 26 eligible trials of moderate quality that enrolled 45,782 participants, the majority of which were elderly and female. Vitamin D use was associated with statistically significant reduction in the risk of falls (odds ratio for suffering at least one fall, 0.86; 95% confidence interval, 0.77-0.96)", "This effect was more prominent in patients who were vitamin D deficient at baseline and in studies in which calcium was coadministered with vitamin D.", "Vitamin D combined with calcium reduces the risk of falls.", "The majority of the evidence is derived from trials enrolling elderly women.", "Studies of vitamin D and calcium for fracture prevention have produced inconsistent results, as a result of different vitamin D status and calcium intake at baseline, different doses and poor to adequate compliance.", "Despite significant increases in the provision of hip protectors and use of vitamin D supplementation in both intervention and control facilities, there was no difference in the number of falls or falls injuries between the intervention and control groups, nor a reduction in falls overall.", "Beyond fall and fracture prevention, vitamin D may also reduce overall morbidity by multiple mechanisms. ", "There is evidence to suggest that these agents may reduce the incidence of nonvertebral fractures and falls; however, their benefit on vertebral fracture reduction may depend on the type of active vitamin D. " ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/20796001", "http://www.ncbi.nlm.nih.gov/pubmed/21795448", "http://www.ncbi.nlm.nih.gov/pubmed/20136906", "http://www.ncbi.nlm.nih.gov/pubmed/22972103", "http://www.ncbi.nlm.nih.gov/pubmed/23922354", "http://www.ncbi.nlm.nih.gov/pubmed/18979152", "http://www.ncbi.nlm.nih.gov/pubmed/20230348", "http://www.ncbi.nlm.nih.gov/pubmed/23728680" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D014807", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004872", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D002762", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D014808" ]

[ "In a subset of patients with severe disease and prone to developing infections prophylactic use of antibiotics may reduce number of exacerbations and improve social and health care costs." ]

[ "Reduction of number of exacerbations" ]

[ "Yet recent well-designed studies have demonstrated that prophylactic antibiotic use is of significant benefit to patients prone to developing infections. Study patients suffered from recurrent urinary tract infections, COPD or were mechanically ventilated in intensive care units. In the first 2 populations, use of antibiotics was associated with an increase in carriage of antibiotic-resistant bacteria, but in intensive care patients the opposite was documented", "Guidelines do not recommend the use of prophylactic antibiotics in COPD but there is preliminary evidence to suggest that they may reduce the number of exacerbations.", "A short prophylactic treatment course with azithromycin is a good alternative in the management of patients with severe, advanced COPD, and could lead to an improvement in social and healthcare costs" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/20477251", "http://www.ncbi.nlm.nih.gov/pubmed/22108462", "http://www.ncbi.nlm.nih.gov/pubmed/11498704" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D029424", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D000900", "http://www.disease-ontology.org/api/metadata/DOID:3083", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D019072" ]

[ "Yes" ]

[ "yes" ]

[ "significant role of frailty as a predictor of depression in a relatively younger old Chinese population", "significant relationships between frailty and depressive symptoms and mortality at 1 year", "These findings suggest that malnutrition is a major predictor of frailty or the \"failure to thrive\" syndrome in older persons. Depression is a major cause of poor nutritional status in older persons.", "Depressed mood was associated with increased risk of steep strength decline, in particular in older men with low body weight. Low body weight in combination with depressed mood may be an indicator of frailty or severe disease status that leads to accelerated strength loss and disability.", "Longitudinally, depressed mood was the only independent predictor of decline in cognition, functional ability, physician-rated health, and mortality;" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/9520923", "http://www.ncbi.nlm.nih.gov/pubmed/24314697", "http://www.ncbi.nlm.nih.gov/pubmed/18684366", "http://www.ncbi.nlm.nih.gov/pubmed/10855595", "http://www.ncbi.nlm.nih.gov/pubmed/11490597" ]

[ { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A15575023", "o": "797" }, { "p": "http://linkedlifedata.com/resource/umls/altMetaMap", "s": "http://linkedlifedata.com/resource/umls/id/C0424594", "o": "http://linkedlifedata.com/resource/umls/label/A15575023" }, { "p": "http://www.w3.org/2008/05/skos-xl#prefLabel", "s": "http://linkedlifedata.com/resource/umls/id/C0424594", "o": "http://linkedlifedata.com/resource/umls/label/A7186488" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C0424594", "o": "http://linkedlifedata.com/resource/umls/label/A17777767" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A7186488", "o": "Frailty" }, { "p": "http://linkedlifedata.com/resource/umls/prefMetaMap", "s": "http://linkedlifedata.com/resource/umls/id/C0424594", "o": "http://linkedlifedata.com/resource/umls/label/A7186488" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A17777767", "o": "R54" }, { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A17777767", "o": "ICD-10-CM" } ]

[ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D003866", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D003863" ]

[ "5-aminolevulinic acid (or 5-ALA) is the generic name of Gliolan. It is approved for fluorescence-guided resections of adult malignant gliomas." ]

[ "5-aminolevulinic acid" ]

[ "BACKGROUND: Five-aminolevulinic acid (Gliolan, medac, Wedel, Germany, 5-ALA) is approved for fluorescence-guided resections of adult malignant gliomas. ", "OBJECTIVE: This study evaluates the cost-effectiveness of 5-aminolevulinic acid (5-ALA, Gliolan®) in patients undergoing surgery for malignant glioma, in standard clinical practice conditions in Spain. ", "OBJECTIVE: To assess effectiveness of 5-aminolevulinic acid (5-ALA, Gliolan(®)) in patients treated for malignant glioma under typical daily practice conditions in Spain, using complete resection rate (CR) and progression free survival at 6 months (PFS6). ", "Today, ALA is approved as Levulan for actinic keratoses, the ALA-methyl ester Metvix for actinic keratoses and basal cell carcinoma, the ALA-hexyl ester Hexvix for the diagnosis of bladder cancer and Gliolan for malignant glioma. ", "MATERIAL AND METHODS: All patients who had undergone 5-ALA fluorescence-guided surgery due to suspected malignant glioma were included. Patients received a standard preoperative dose of Gliolan. ", "Today, ALA is approved as Levulan for actinic keratoses, the ALA-methyl ester Metvix for actinic keratoses and basal cell carcinoma, the ALA-hexyl ester Hexvix for the diagnosis of bladder cancer and Gliolan for malignant glioma" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/24468659", "http://www.ncbi.nlm.nih.gov/pubmed/22849976", "http://www.ncbi.nlm.nih.gov/pubmed/18389144", "http://www.ncbi.nlm.nih.gov/pubmed/25248327", "http://www.ncbi.nlm.nih.gov/pubmed/23870657" ]

[]

[]

[ "Yes. Activation-induced miR-155 targets the chromatin protein Jarid2 to regulate proinflammatory cytokine production in T helper 17 cells." ]

[ "yes" ]

[ "Jarid2 links MicroRNA and chromatin in Th17 cells.", "In this issue of Immunity, Escobar et al. (2014) bring microRNAs and chromatin together by showing how activation-induced miR-155 targets the chromatin protein Jarid2 to regulate proinflammatory cytokine production in T helper 17 cells.", "miR-155 activates cytokine gene expression in Th17 cells by regulating the DNA-binding protein Jarid2 to relieve polycomb-mediated repression.", "Mir155 was bound by Th17 cell transcription factors and was highly expressed during Th17 cell differentiation. miR-155-deficient Th17 and T regulatory (Treg) cells expressed increased amounts of Jarid2, a DNA-binding protein that recruits the Polycomb Repressive Complex 2 (PRC2) to chromatin. PRC2 binding to chromatin and H3K27 histone methylation was increased in miR-155-deficient cells, coinciding with failure to express Il22, Il10, Il9, and Atf3. Defects in Th17 cell cytokine expression and Treg cell homeostasis in the absence of Mir155 could be partially suppressed by Jarid2 deletion. Thus, miR-155 contributes to Th17 cell function by suppressing the inhibitory effects of Jarid2.", "Thus, miR-155 contributes to Th17 cell function by suppressing the inhibitory effects of Jarid2.", "Thus, miR-155 contributes to Th17 cell function by suppressing the inhibitory effects of Jarid2.", "Defects in Th17 cell cytokine expression and Treg cell homeostasis in the absence of Mir155 could be partially suppressed by Jarid2 deletion. Thus, miR-155 contributes to Th17 cell function by suppressing the inhibitory effects of Jarid2.", "Thus, miR-155 contributes to Th17 cell function by suppressing the inhibitory effects of Jarid2." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/24856900", "http://www.ncbi.nlm.nih.gov/pubmed/24950205" ]

[]

[ "http://www.uniprot.org/uniprot/JARD2_CHICK", "http://www.uniprot.org/uniprot/JARD2_HUMAN", "http://amigo.geneontology.org/amigo/term/GO:2000317", "http://www.uniprot.org/uniprot/JARD2_MOUSE", "http://amigo.geneontology.org/amigo/term/GO:0072538", "http://amigo.geneontology.org/amigo/term/GO:2000318", "http://amigo.geneontology.org/amigo/term/GO:2000316", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D058504", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D018417" ]

[ "Engineered DNA-binding molecule-mediated chromatin immunoprecipitation (enChIP) is a novel method for purification of specific genomic regions retaining molecular interactions. EnChIP using the CRISPR system efficiently isolates specific genomic regions. In this form of enChIP, specific genomic regions are immunoprecipitated with antibody against a tag(s), which is fused to a catalytically inactive form of Cas9 (dCas9), which is co-expressed with a guide RNA (gRNA) and recognizes endogenous DNA sequence in the genomic regions of interest. enChIP-mass spectrometry (enChIP-MS) targeting endogenous loci identified associated proteins. enChIP using the CRISPR system would be a convenient and useful tool for dissecting chromatin structure of genomic regions of interest." ]

[]

[ "Identification of telomere-associated molecules by engineered DNA-binding molecule-mediated chromatin immunoprecipitation (enChIP).", "Here, we report isolation of telomeres by engineered DNA-binding molecule-mediated chromatin immunoprecipitation (enChIP) using a transcription activator-like (TAL) protein recognizing telomere repeats. Telomeres recognized by the tagged TAL protein were immunoprecipitated with an antibody against the tag and subjected to identification of telomere-binding molecules. enChIP-mass spectrometry (enChIP-MS) targeting telomeres identified known and novel telomere-binding proteins.", "Efficient isolation of specific genomic regions and identification of associated proteins by engineered DNA-binding molecule-mediated chromatin immunoprecipitation (enChIP) using CRISPR.", "Here, we established a novel method, engineered DNA-binding molecule-mediated chromatin immunoprecipitation (enChIP), for purification of specific genomic regions retaining molecular interactions. We showed that enChIP using the CRISPR system efficiently isolates specific genomic regions. In this form of enChIP, specific genomic regions are immunoprecipitated with antibody against a tag(s), which is fused to a catalytically inactive form of Cas9 (dCas9), which is co-expressed with a guide RNA (gRNA) and recognizes endogenous DNA sequence in the genomic regions of interest. enChIP-mass spectrometry (enChIP-MS) targeting endogenous loci identified associated proteins. enChIP using the CRISPR system would be a convenient and useful tool for dissecting chromatin structure of genomic regions of interest.", "Recently, we developed the engineered DNA-binding molecule-mediated chromatin immunoprecipitation (enChIP) technology for purification of specific genomic regions.", "Here, we established a novel method, engineered DNA-binding molecule-mediated chromatin immunoprecipitation (enChIP), for purification of specific genomic regions retaining molecular interactions. ", "Recently, we developed the engineered DNA-binding molecule-mediated chromatin immunoprecipitation (enChIP) technology for purification of specific genomic regions.", "Here, we established a novel method, engineered DNA-binding molecule-mediated chromatin immunoprecipitation (enChIP), for purification of specific genomic regions retaining molecular interactions.", "In this form of enChIP, specific genomic regions are immunoprecipitated with antibody against a tag(s), which is fused to a catalytically inactive form of Cas9 (dCas9), which is co-expressed with a guide RNA (gRNA) and recognizes endogenous DNA sequence in the genomic regions of interest. enChIP-mass spectrometry (enChIP-MS) targeting endogenous loci identified associated proteins.", "Recently, we developed the engineered DNA-binding molecule-mediated chromatin immunoprecipitation (enChIP) technology for purification of specific genomic regions. Here, we developed a retroviral expression system for enChIP using CRISPR.", "Here, we established a novel method, engineered DNA-binding molecule-mediated chromatin immunoprecipitation (enChIP), for purification of specific genomic regions retaining molecular interactions. We showed that enChIP using the CRISPR system efficiently isolates specific genomic regions." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/23942116", "http://www.ncbi.nlm.nih.gov/pubmed/25051498", "http://www.ncbi.nlm.nih.gov/pubmed/24201379" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D047369" ]

[ "The human HOXD complex contains nine genes: HOXD1, HOXD3, HOXD4, HOXD8, HOXD9, HOXD10, HOXD11, HOXD12 and HOXD13, which are clustered from 3′ to 5′ in an approximately 100-kb stretch on chromosome 2q31.1 with HOXD1 at the 3' end and HOXD13 the 5′ end." ]

[ "9" ]

[ "Both children are heterozygous for a deletion that eliminates at least eight (HOXD3-HOXD13) of the nine genes in the HOXD cluster" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/10364522", "http://www.ncbi.nlm.nih.gov/pubmed/22879880" ]

[]

[]

[ "No. The isotretinoin has severe teratogenic effects and it is not safe to use during pregnancy." ]

[ "no" ]

[ "Isotretinoin is a remarkably effective drug for severe, recalcitrant acne vulgaris.", "a number of important adverse effects were reported", "even the most recent pregnancy prevention program (iPledge) is no more successful than prior programs; there will likely always be a small number of female patients becoming pregnant while receiving isotretinoin for acne vulgaris.", "Isotretinoin has revolutionized the management of acne vulgaris.", "The adverse effect(s) that led to patients stopping isotretinoin were cheilitis (22 patients), mood change (13), tiredness (12), eczema (6) and pregnancy (2).", "Downregulation of FGFR2b-signaling by isotretinoin explains its therapeutic effect in acne. Downregulation of FGFR2b-signaling during the first trimester of pregnancy disturbs branched morphogenesis and explains retinoid embryotoxicity.", "The isotretinoin, a 13-cis-retinoic acid, has revolutionized the management of severe treatment-resistant acne and it has been widely used for a range of dermatological conditions, in 90% of the time in young women between 13 and 45 years of age. This agent has severe teratogenic effects, as serious craniofacial, cardiovascular, thymic and central nervous system malformations.", "malformations is 3-5%, but it increases to almost 30% in women exposed to isotretinoin during the first trimester of pregnancy. Generally, patients in treatment with isotretinoin avoid eventual pregnancy during assumption and, after its stopping, fertility and foetal development are normal once circulating isotretinoin levels return to normal.", "After 3 months of pharmacological wash out, patient become pregnant and manifested this severe malformation. Woman interrupted gestation, by labour induction.", "Clindamycin phosphate 1.2% together with tretinoin 0.025% as a gel (CTG) is a topical formulation of a fixed and stable combination approved by the FDA for the treatment of acne vulgaris in patients 12 years of age or older.", "Safety of CTG use in pregnancy has not been established.", "To estimate the population-based incidence rates of pregnancy, spontaneous and elective abortions, and birth defects associated with isotretinoin use, and to determine predictors of pregnancy while on isotretinoin", "Pregnancies, spontaneous and elective abortions, and birth defects were identified using procedure codes and medical diagnoses.", "90 women who became pregnant while on the drug, 76 terminated the pregnancy (84%), three had a spontaneous abortion (3%), two had trauma during delivery resulting in neonatal deaths (2%) and nine had a live birth (10%). Among the live births, only one had a congenital anomaly of the face and neck (11%).", "elective abortion rates were also much higher in our study.", "Topical antibiotics, isotretinoin or systemic antibiotics are usually used for acne therapy. However, isotretinoin cannot be used during pregnancy because it can cause significant birth defects while systemic antibiotics can have adverse side effects such as gastrointestinal irritation, photosensitivity and tetracycline sensitivity.", "Isotretinoin has been used to treat acne since 1982. Its current indications in the package insert are limited and many physicians still feel uncomfortable prescribing it because of its side effects.", "Aside from its teratogenic effect, isotretinoin is a safe and excellent drug for acne therapy. I", "a pregnancy test in females.", "Vitamin A and its derivatives, retinoic acid, tretinoin and isotretinoin, are currently used in dermatological treatments. The administration of high doses of this vitamin provokes congenital malformations in mice: cleft palate, maxillary and mandibular hypoplasia and total or partial fusion of the maxillary incisors.", "Twelve 60-day-old female Mus musculus were divided into two groups on the 7th day of pregnancy: treated group--1 mg isotretinoin per kg body weight, dissolved in vegetable oil, was administered from the 7th to the 13th day of pregnancy; control group--vegetable oil in equivalent volume was administered orally for the same period. On the 16th day of pregnancy, the females were sacrificed, the fetuses were removed and their heads amputated.", "The results showed that both groups had closed palates with no reminiscence of epithelial cells; however, the first molar germs of the isotretinoin-treated animals showed delayed development compared to the control animals.", "Isotretinoin (13-cis-RA) is teratogenic in all species examined; based on administered dose, humans appear most sensitive, followed by (in order or decreasing sensitivity) monkey, rabbit, hamster, mouse, and rat.", "Based on embryonic delivered dose, we suggest that 13-cis-RA is an equipotent teratogen in hamster and rabbit.", "its safety in humans is occasionally questioned because oral ingestion of retinoids at therapeutic levels is known to entail teratogenic risks.", "topical tretinoin is not a potential human developmental toxicant.", "Teratogenicity of vitamin A was firstly detected in experimental animals in 1953. Nearly 30 years later, teratogenicity of vitamin A analogue-isotretinoin was reported in humans. Isotretinoin induces serious birth defects of craniofacial and central nervous system, cardiovascular system and thymic malformations--in about 25% of babies exposed during the first trimester of their prenatal development.", "high vitamin A intake in pregnant woman: Women who use daily vitamin A supplements during early pregnancy have approximately a two-fold increased risk of giving birth to a malformed baby.", "Vitamin A started to affect development between doses 0.3-0.3 microm [corrected] per embryo. Malformations of head, extremities and heart were detected similarly like in laboratory mammals and in man", "the minimal embryotoxic doses of vitamin A in mammals were estimated to be between 0.1-1 mg/kg of maternal weight", "Human epidemiological studies have proved teratogenicity of vitamin A after daily doses 25,000 i.u.-8.3 mg (0.13 mg/kg)- and reduction of its maximum intake has been recommended to 10,000 i.u. per day (0.05 mg/kg). The results about teratogenicity of vitamin A achieved in the chick embryo are in agreement with such a recommendation. Intake of vitamin A in the food is sufficient for pregnant woman in common Czech population. Therefore, an artificial supplementation of vitamin A brings risk of overdosage. If supplementation by vitamin A is unavoidable during pregnancy, B-carotene should be preferred.", "a teratogenic dosing regimen with 13-cis-RA [Hummler et al. (1994) Teratology 50:184-193].", "plasma AUC values of all-trans-RA were 2- to 7-fold higher after all-trans-RA administration (present study) than after dosing with the teratogenic dose of 13-cis-RA. These results strengthen our recent suggestion that the teratogenic effects induced in cynomolgus monkeys by 13-cis-RA treatment cannot solely result from the action of all-trans-RA, but may involve 13-cis-RA and 13-cis-4-oxo-RA, which could act directly or function as transport vehicle.", "VITA, among others, is involved in the process of morphogenesis. In contrast, synthetic derivatives of VITA, specifically Tigasone (etretinate, TIG) and Roaccutane (isotretinoin, ROA), are regarded as major teratogens.", "A biphasic maximal inhibition was present at 1 microM concentrations when the retinoids VITA, TIG and ROA were added for 16 h (52, 58 and 57%, respectively; P < 0.01 by one-way analysis of variance). In contrast, the addition of the three retinoids at 1 microM concentrations for 16 h had no significant effect on HCG secretion by placental explants of 11-13 weeks gestational age.", "Inhibition of HCG secretion by retinoids may contribute either directly or indirectly to their teratogenicity.", "Isotretinoin is a potent retinoic acid used in the treatment of skin disorders. Though very effective, it is teratogenic if administered during pregnancy, and its teratogenic effect may be related to the normal activity of retinoids as signalling molecules in the embryo.", "defects that includes heart defects, by inhibiting the migration of neural crest cells.", "Proliferation in heart tissue of whole embryo cultures was inhibited in medium with 10(-6) M isotretinoin to 62% of the control level in myocardium.", "The results suggest multiple effects of retinoids on growth, morphogenesis, and differentiation of early cardiac tissue, and are discussed in relation to the potential role of retinoids in early embryogenesis.", "Oral administration of 400 mg/kg of 13-cis retinoic acid to 9 day pregnant mice gives rise to important maxillofacial malformations. The first manifestation of teratogenic effect is an increase of density of cell death arising in the dorsal part of the first two branchial arches at day 9.5. These two arches become hypoplastic at days 10 and 11, and the preskeletal anlagen appear too late in comparison to control embryos. Meckel's cartilage is too curvilinear and medially situated. Pre-ossicular and pre-mandibular blastemata develop with spatial distortions which are well analyzable at days 16 and 17", "Isotretinoin (13-cis-retinoic acid, Accutane) increases the risk of major congenital malformations in infants exposed to isotretinoin during pregnancy. However, there have been no epidemiologic reports to date on the effect of a subsequent pregnancy after discontinuation of isotretinoin.", "analysis of pregnancy case reports from patients in whom conception occurred after isotretinoin treatment had been discontinued", "spontaneous and missed abortions from all pregnancies was 9.1% (eight patients), and the incidence rate of congenital malformation among the live births was 5.0% (four patients).", "were not significantly different from the rates reported for women of reproductive age in the general population. In addition, the malformations reported were not characteristic of retinoic acid-induced congenital anomalies.", "Keratolenticular dysgenesis (Peters' anomaly) was induced in mice by exposure to the human teratogens, ethanol or 13-cis retinoic acid (isotretinoin, Accutane). Acute teratogen exposure on the seventh day of gestation (corresponding to the third week of human gestation) resulted in an eye malformation incidence of 46% to 100% in day 14 fetuses", "This secondary effect on neural crest derivatives is exhibited in the adult animals as corneal opacities associated with defects in Descemet's membrane and endothelium, and anterior polar cataracts.", "13-cis-retinoic acid (13-cis-RA, or isotretinoin) is responsible for various craniofacial malformations in the rodent and human embryo.", "In whole embryo culture, 13-cis-RA caused significant overall embryonic growth retardation, especially in the primary and secondary palatal processes.", "subsequent cell growth was decreased at concentrations of 13-cis-RA greater than 1 X 10(-5) M. After a 40-hr treatment period, labeling indices in retinoid-treated cells were significantly lower than control values (25% compared with 40%). Retinoic acid also caused a significant, concentration-dependent decrease in 3H-thymidine incorporation. The inhibitory effect of 13-cis-RA on proliferation of oral-nasal mesenchymal cells appears to be related to the production of craniofacial malformations.", "Reports of adverse human pregnancy outcomes including cleft palate have increased as the clinical use of isotretinoin (13-cis-retinoic acid) and other retinoic acid (RA) derivatives have increased, but the mechanisms by which their effects are exerted are not understood.", "In shelves exposed to EGF and trans-RA early in their development, DNA synthesis appears to terminate prematurely as compared to shelves cultured in control media, and this effect is accompanied by excessive mesenchymal extracellular space expansion. Exposure of shelves to EGF alone is sufficient to block degeneration and induce hyperplasia of the medial epithelial cells but does not induce other ultrastructural changes seen with both EGF and RA. The observed alterations in medial cell morphology could interfere with adhesion of the palatal shelves and may play a role in retinoid-induced cleft palate in the human embryo.", "Recent clinical observations strongly suggest that isotretinoin [13-cis-retinoic acid (cis RA)] is a human teratogen causing primarily heart and craniofacial malformations including ear and palatal defects.", "Our results demonstrate that labeled cis RA enters the tissues of the embryo both in vivo and in vitro. Cis RA inhibited proliferation of the frontonasal mesenchyme cells in primary culture with 31% inhibition occurring at 2 X 10(-5) M cis RA.", "Retinoic acid, an analogue of vitamin A, is known to be teratogenic in laboratory animals and has recently been implicated in a few clinical case reports. To study the human teratogenicity of this agent, we investigated 154 human pregnancies with fetal exposure to isotretinoin, a retinoid prescribed for severe recalcitrant cystic acne. The outcomes were 95 elective abortions, 26 infants without major malformations, 12 spontaneous abortions, and 21 malformed infants. A subset of 36 of the 154 pregnancies was observed prospectively.", "Exposure to isotretinoin was associated with an unusually high relative risk for a group of selected major malformations (relative risk = 25.6; 95 per cent confidence interval, 11.4 to 57.5).", "It is possible that a major mechanism of isotretinoin teratogenesis is a deleterious effect on cephalic neural-crest cell activity that results in the observed craniofacial, cardiac, and thymic malformations." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/3209676", "http://www.ncbi.nlm.nih.gov/pubmed/18937624", "http://www.ncbi.nlm.nih.gov/pubmed/3459732", "http://www.ncbi.nlm.nih.gov/pubmed/23559397", "http://www.ncbi.nlm.nih.gov/pubmed/2923442", "http://www.ncbi.nlm.nih.gov/pubmed/17214828", "http://www.ncbi.nlm.nih.gov/pubmed/21198520", "http://www.ncbi.nlm.nih.gov/pubmed/12171680", "http://www.ncbi.nlm.nih.gov/pubmed/19961047", "http://www.ncbi.nlm.nih.gov/pubmed/7962395", "http://www.ncbi.nlm.nih.gov/pubmed/2102396", "http://www.ncbi.nlm.nih.gov/pubmed/9439011", "http://www.ncbi.nlm.nih.gov/pubmed/9035347", "http://www.ncbi.nlm.nih.gov/pubmed/20436882", "http://www.ncbi.nlm.nih.gov/pubmed/3162101", "http://www.ncbi.nlm.nih.gov/pubmed/3162748", "http://www.ncbi.nlm.nih.gov/pubmed/11445913", "http://www.ncbi.nlm.nih.gov/pubmed/15545101", "http://www.ncbi.nlm.nih.gov/pubmed/3501432", "http://www.ncbi.nlm.nih.gov/pubmed/9091512", "http://www.ncbi.nlm.nih.gov/pubmed/9299599", "http://www.ncbi.nlm.nih.gov/pubmed/1473624" ]

[ { "p": "http://www4.wiwiss.fu-berlin.de/drugbank/resource/drugbank/description", "s": "http://www4.wiwiss.fu-berlin.de/drugbank/resource/drugs/DB00982", "o": "Isotretinoin is a medication used for the treatment of severe acne. It is sometimes used in prevention of certain skin cancers. It is a retinoid, meaning it derives from vitamin A and is found in small quantities naturally in the body. Isotretinoin binds to and activates nuclear retinoic acid receptors (RAR), thereby regulating cell proliferation and differentiation. This agent also exhibits immunomodulatory and anti-inflammatory responses and inhibits ornithine decarboxylase, thereby decreasing polyamine synthesis and keratinization." }, { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A11572307", "o": "FDA Structured Product Labels" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A12802988", "o": "Isotretinoin" }, { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A17902718", "o": "National Drug File - Reference Terminology" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C0022265", "o": "http://linkedlifedata.com/resource/umls/label/A17902718" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://linkedlifedata.com/resource/pubmed/chemical/Isotretinoin", "o": "Isotretinoin" }, { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#type", "s": "http://linkedlifedata.com/resource/umls/label/A0599177", "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/A17035190", "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/A18361057", "o": "http://www.w3.org/2008/05/skos-xl#Label" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A10769142", "o": "ISOTRETINOIN" } ]

[ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0007565", "http://www.biosemantics.org/jochem#4165261", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011247", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D015474", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011259", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D061685" ]

[ "The p53 tumour suppressor protein is tightly controlled by the E3 ubiquitin ligase, mouse double minute 2 (MDM2). The RING domain E3 ubiquitin ligase Mdm2 is the master regulator of the tumor suppressor p53. It targets p53 for proteasomal degradation, restraining the potent activity of p53 and enabling cell survival and proliferation. p53 is inactivated in many human malignancies through missense mutations or overexpression of the human homologue of Mdm2 (Hdm2), an E3 ubiquitin ligase that ubiquitinates p53, thereby promoting its proteasomal degradation.", "This is well illustrated by the E3 ubiquitin ligase MDM2 that targets p53 for proteasomal degradation under normal conditions and is essential for controlling p53 activity during development., p53 is inactivated in many human malignancies through missense mutations or overexpression of the human homologue of Mdm2 (Hdm2), an E3 ubiquitin ligase that ubiquitinates p53, thereby promoting its proteasomal degradation., Mdm2 has been thought to regulate the tumor suppressor p53 in two ways: by masking p53's access to transcriptional machinery, and by ubiquitinating p53, targeting it for proteasomal degradation" ]

[ "The mouse double minute 2 (mdm2)", "The human homologue of Mdm2 (Hdm2)" ]

[ "p53 levels and activity are controlled in large part through regulated ubiquitination and subsequent destruction by the 26S proteasome. Monoubiquitination of p53 is mediated primarily by the RING-finger E3 ubiquitin ligase MDM2 and impacts p53 activity through modulation of p53 localization and transcription activities. ", "The RING domain E3 ubiquitin ligase Mdm2 is the master regulator of the tumor suppressor p53. It targets p53 for proteasomal degradation, restraining the potent activity of p53 and enabling cell survival and proliferation.", "The p53 transcription factor and tumor suppressor is regulated primarily by the E3 ubiquitin ligase Mdm2, which ubiquitinates p53 to target it for proteasomal degradation. Aside from its ubiquitin ligase function, Mdm2 has been believed to be capable of suppressing p53's transcriptional activity by binding with and masking the transactivation domain of p53.", "The regulation of p53 expression levels is critical in controlling p53 activity in normal and damaged cells. This is well illustrated by the E3 ubiquitin ligase MDM2 that targets p53 for proteasomal degradation under normal conditions and is essential for controlling p53 activity during development.", "p53 is inactivated in many human malignancies through missense mutations or overexpression of the human homologue of Mdm2 (Hdm2), an E3 ubiquitin ligase that ubiquitinates p53, thereby promoting its proteasomal degradation.", "Mdm2 has been thought to regulate the tumor suppressor p53 in two ways: by masking p53's access to transcriptional machinery, and by ubiquitinating p53, targeting it for proteasomal degradation. This dogma was recently challenged by data generated from knockin mice in which Mdm2's RING E3 ubiquitin ligase activity was abrogated by a single point mutation. The RING mutant Mdm2 is fully capable of binding with p53, yet cannot suppress p53 activity, suggesting that Mdm2 cannot block p53 by binding alone, without ubiquitination.", "MDM2 is an E3 ubiquitin ligase that regulates the proteasomal degradation and activity of proteins involved in cell growth and apoptosis, including the tumor suppressors p53 and retinoblastoma and the transcription factor E2F1. ", "The p53 tumor suppressor protein has a major role in protecting genome integrity. Under normal circumstances Mdmx and Mdm2 control the activity of p53. Both proteins inhibit the transcriptional regulation by p53, while Mdm2 also functions as an E3 ubiquitin ligase to target both p53 and Mdmx for proteasomal degradation. ", "p53 is a critical coordinator of a wide range of stress responses. To facilitate a rapid response to stress, p53 is produced constitutively but is negatively regulated by MDM2. MDM2 can inhibit p53 in multiple independent ways: by binding to its transcription activation domain, inhibiting p53 acetylation, promoting nuclear export, and probably most importantly by promoting proteasomal degradation of p53. The latter is achieved via MDM2's E3 ubiquitin ligase activity harbored within the MDM2 RING finger domain.", "Mdm2 is a RING finger E3 ubiquitin ligase, which promotes ubiquitination and proteasomal degradation of the p53 tumor suppressor protein. Acetylation of p53 regulates p53's transcriptional activity and inhibits Mdm2-mediated p53 ubiquitination and degradation.", "MDM2 is an E3 ubiquitin ligase that targets p53 for proteasomal degradation. Recent studies have shown, however, that the ring-finger domain (RFD) of MDM2, where the ubiquitin E3 ligase activity resides, is necessary but not sufficient for p53 ubiquitination, suggesting that an additional activity of MDM2 might be required.", "The Mdm2 proto-oncogene is amplified and over-expressed in a variety of tumors. One of the major functions of Mdm2 described to date is its ability to modulate the levels and activity of the tumor suppressor protein p53. Mdm2 binds to the N-terminus of p53 and, through its action as an E3 ubiquitin ligase, targets p53 for rapid proteasomal degradation. ", "The HDM2-p53 loop is crucial for monitoring p53 level and human pathologies. Therefore, identification of novel molecules involved in this regulatory loop is necessary for understanding the dynamic regulation of p53 and treatment of human diseases. Here, we characterized that the ribosomal protein L6 binds to and suppresses the E3 ubiquitin ligase activity of HDM2, and subsequently attenuates HDM2-mediated p53 polyubiquitination and degradation. ", "Together, our study identifies the crucial function of RPL6 in regulating HDM2-p53 pathway, which highlights the importance of RPL6 in human genetic diseases and cancers.", "Targeting the E3 ubiquitin ligase HDM2 can lead to a therapeutic surge in p53 levels. However, the efficacy of HDM2 inhibition can be compromised by overexpression of HDMX, an HDM2 homolog that binds and sequesters p53.", "The p53 tumour suppressor protein is tightly controlled by the E3 ubiquitin ligase, mouse double minute 2 (MDM2), but maintains MDM2 expression as part of a negative feedback loop. ", "Murine double minute (MDM2) is an E3 ligase that promotes ubiquitination and degradation of tumor suppressor protein 53 (p53).", "This is well illustrated by the E3 ubiquitin ligase MDM2 that targets p53 for proteasomal degradation under normal conditions and is essential for controlling p53 activity during development.", "Mdm2 is a RING finger E3 ubiquitin ligase, which promotes ubiquitination and proteasomal degradation of the p53 tumor suppressor protein", "MDM2 is an E3 ubiquitin ligase that regulates the proteasomal degradation and activity of proteins involved in cell growth and apoptosis, including the tumor suppressors p53 and retinoblastoma and the transcription factor E2F1", "The p53 transcription factor and tumor suppressor is regulated primarily by the E3 ubiquitin ligase Mdm2, which ubiquitinates p53 to target it for proteasomal degradation" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/18235222", "http://www.ncbi.nlm.nih.gov/pubmed/16082221", "http://www.ncbi.nlm.nih.gov/pubmed/22819825", "http://www.ncbi.nlm.nih.gov/pubmed/23150437", "http://www.ncbi.nlm.nih.gov/pubmed/11948425", "http://www.ncbi.nlm.nih.gov/pubmed/12832479", "http://www.ncbi.nlm.nih.gov/pubmed/21075307", "http://www.ncbi.nlm.nih.gov/pubmed/15632057", "http://www.ncbi.nlm.nih.gov/pubmed/19934289", "http://www.ncbi.nlm.nih.gov/pubmed/15013777", "http://www.ncbi.nlm.nih.gov/pubmed/19166840", "http://www.ncbi.nlm.nih.gov/pubmed/24174547", "http://www.ncbi.nlm.nih.gov/pubmed/22666487", "http://www.ncbi.nlm.nih.gov/pubmed/16339144", "http://www.ncbi.nlm.nih.gov/pubmed/23671280", "http://www.ncbi.nlm.nih.gov/pubmed/23581014" ]

[]

[]

[ "The DNA unwinding suggests DNA intercalation, which could explain the inhibition of topoisomerase II. Among its many properties, amiloride is a DNA intercalator and topoisomerase II inhibitor. Amsacrine, a DNA intercalator and topoisomerase II inhibitor, is efficacious as an antileukemogenic agent. AQ4N (1,4-bis[[2-(dimethylamino)ethyl] amino]-5,8-dihydroxyanthracene-9, 10-dione bis-N-oxide dihydrochloride) is a prodrug which is selectively activated within hypoxic tissues to AQ4, a topoisomerase II inhibitor and DNA intercalator. Amonafide is a DNA intercalator and topoisomerase II inhibitor in clinical development for the treatment of neoplastic diseases." ]

[ "yes" ]

[ "The aporphine alkaloids (+)-dicentrine and (+)-bulbocapnine are non-planar molecules lacking features normally associated with DNA binding by intercalation or minor groove binding. Surprisingly, dicentrine showed significant activity as a topoisomerase II (EC 5.99.1.3) inhibitor and also was active in a DNA unwinding assay.", "The DNA unwinding suggests DNA intercalation, which could explain the inhibition of topoisomerase II.", "We found that several agents, including adriamycin (a DNA intercalator and inhibitor of topoisomerase II)", "Amsacrine, a DNA intercalator and topoisomerase II inhibitor, is efficacious as an antileukemogenic agent.", "Quinacrine was less effective. (ii) Inhibitors intercalating and binding to the 'cleavable' DNA-topoisomerase complex (m-AMSA, mitoxantrone, doxorubicin and daunorubicin) strongly suppressed reparative DNA incision. ", "DNA intercalation and inhibition of topoisomerase II.", "Among its many properties, amiloride is a DNA intercalator and topoisomerase II inhibitor.", "To determine whether the ability of amiloride to intercalate into DNA and to inhibit DNA topoisomerase II was dependent on the ability to assume a cyclized conformation, we studied the structure-activity relationship for 12 amiloride analogs", "Empirical assays consisting of biophysical, biochemical, and cell biological approaches, as well as computational molecular modeling approaches, were used to determine conformational properties for these molecules, and to determine whether they intercalated into DNA and inhibited topoisomerase II. ", "Results indicated that only those analogs capable of cyclization could intercalate into DNA and inhibit topoisomerase II. Thus, the ability of amiloride and the 12 analogs studied to intercalate into DNA and to inhibit topoisomerase II appears dependent on the ability to exist in a planar, hydrogen-bonded, tricyclic conformation.", "Abnormal expression of the nuclear-associated enzyme DNA topoisomerase II (topoisomerase II) has been implicated in the in vitro phenotype of radiation hypersensitive ataxia-telangiectasia (A-T) cells and in modifying sensitivity of eukaryotic cells to topoisomerase II-inhibitor drugs [e.g., the DNA intercalator amsacrine (mAMSA)]. ", "All three tested anthraquinones, emodin, aloe-emodin, and danthron, showed capabilities to inhibit the non-covalent binding of bisbenzimide Hoechst 33342 to isolated DNA and in mouse lymphoma L5178Y cells comparable to the topoisomerase II inhibitor and intercalator m-amsacrine.", "These studies suggest that AD 288 inhibits topoisomerase II activity by preventing the initial non-covalent binding of topoisomerase II to DNA. Since AD 288 is a potent DNA intercalator, catalytic inhibition is achieved by prohibiting access of the enzyme to DNA binding sites. ", "AQ4N (1,4-bis[[2-(dimethylamino)ethyl] amino]-5,8-dihydroxyanthracene-9, 10-dione bis-N-oxide dihydrochloride) is a prodrug which is selectively activated within hypoxic tissues to AQ4, a topoisomerase II inhibitor and DNA intercalator.", "Amonafide is a DNA intercalator and topoisomerase II inhibitor in clinical development for the treatment of neoplastic diseases.", " We found that three compounds had similar cancer cell-selective growth inhibition to amonafide, while retaining similar subcellular localization, DNA intercalation and topoisomerase II inhibition activities.", "Amonafide is a novel topoisomerase II (Topo II) inhibitor and DNA intercalator that induces apoptotic signaling by blocking the binding of Topo II to DNA.", "At higher concentrations, inhibition of Top1 catalytic activity and DNA intercalation is observed.", "Design, synthesis and biological evaluation of new oligopyrrole carboxamides linked with tricyclic DNA-intercalators as potential DNA ligands or topoisomerase inhibitors.", "It was found that 1) morpholinyldoxorubicin, cyanomorpholinyldoxorubicin, and Actinomycin D (but not doxorubicin) stimulated DNA topoisomerase I-induced cleavage at specific DNA sites; 2) only doxorubicin and Actinomycin D stimulated DNA cleavage by DNA topoisomerase II; 3) at higher drug concentrations, DNA intercalators suppressed enzyme-mediated DNA cleavage induced by DNA topoisomerase I, as well as topoisomerase II; 4) only cyanomorpholinyldoxorubicin produced DNA-DNA cross-links; no DNA unwinding could be observed; and 5) DNA intercalation (unwinding) potency of morpholinyldoxorubicin was about 2-fold less than that of doxorubicin.", "The data indicate that some DNA intercalators are not only inhibitors of DNA topoisomerase II but act also on DNA topoisomerase I.", "The screen of cMAP for uncharacterized drugs indicated the signature of Epoxy anthraquinone derivative (EAD) matched the profiles of multiple known DNA targeted agents (topoisomerase I/II inhibitors, DNA intercalators, and DNA alkylation agents) as predicted by its structure.", "Cytotoxicity of several classes of antitumor DNA intercalators is thought to result from disturbance of DNA metabolism following trapping of the nuclear enzyme DNA topoisomerase II as a covalent complex on DNA.", "Most DNA intercalators and epipodophyllotoxins inhibit mammalian topoisomerase II by trapping the enzyme within DNA cleavage complexes that can be detected in cells as protein-associated DNA strand breaks.", "Many compounds capable of inhibiting DNA topoisomerase II are DNA intercalators.", "Numerous topoisomerase I poisons including DNA minor groove binders such as Hoechst 33258 and DNA intercalators such as benzophenanthridine alkaloids and indolocarbazole derivatives have been discovered and developed.", "The stabilization of cleavage intermediates by intercalators may have a common mechanism for DNA topoisomerase I and DNA topoisomerase II.", "Because structurally related antitumor alkaloids such as camptothecin and fagaronine are known to function as intercalative topoisomerase poisons, it is hypothesized that cytotoxic Stauranthus alkaloids may also serve as intercalative topoisomerase inhibitors.", "Taken together, our results suggest that much of the activity and specificity of m-AMSA as a topoisomerase II poison is embodied in the headgroup, while DNA intercalation is used primarily to increase the affinity of m-AMSA for the topoisomerase II-DNA cleavage complex.", "The cross-sensitivity patterns of the mutant were examined for covalently (anthramycin) and non-covalently (distamycin A) binding minor groove ligands, and DNA intercalating [adriamycin, mitoxantrone and 4'-(9-acridinylamino)methanesulphon-m-anisidide (mAMSA)] and non-intercalating (VP16-213) topoisomerase II poisons.", "Quinoline alkaloids as intercalative topoisomerase inhibitors.", "DNA intercalation and inhibition of topoisomerase II. Structure-activity relationships for a series of amiloride analogs.", "These include: (i) the production of improved topoisomerase inhibitors (by consideration of drug/protein as well as drug/DNA interactions); (ii) the development of reductively-activated chromophores as hypoxia-selective agents; and (iii) the use of DNA-intercalators of known DNA binding orientation as 'carriers' for the delivery of other reactive functionality specifically (sequence-, regio- and site-specifically) to DNA.", "Indolo[2,3-b]quinolines are a family of DNA intercalators and inhibitors of topoisomerase II, synthetic analogs of neocryptolepine, an alkaloid traditionally used in African folk medicine.", "Their ability to function as bis-intercalators was assessed by a novel and convenient topoisomerase fluorescent assay.", "Structure-activity relationship of polypyridyl ruthenium(II) complexes as DNA intercalators, DNA photocleavage reagents, and DNA topoisomerase and RNA polymerase inhibitors.", "In addition, fragments of about 900 kbp were detected in the cells treated with a topoisomerase inhibitor, 4'-(9-acridinylamino)methane-sulfon-m-anisidine, and fragments in the broad size range between 700 and 245 kbp in the cells treated with radical producers, bleomycin and neocarzinostatin. ", "The data indicate that some DNA intercalators are not only inhibitors of DNA topoisomerase II but act also on DNA topoisomerase I. ", "Long-term inhibition of DNA synthesis and the persistence of trapped topoisomerase II complexes in determining the toxicity of the antitumor DNA intercalators mAMSA and mitoxantrone.", "Effects of the DNA intercalators 4'-(9-acridinylamino)methanesulfon-m-anisidide and 2-methyl-9-hydroxyellipticinium on topoisomerase II mediated DNA strand cleavage and strand passage.", "Most DNA intercalators and epipodophyllotoxins inhibit mammalian topoisomerase II by trapping the enzyme within DNA cleavage complexes that can be detected in cells as protein-associated DNA strand breaks. ", "Here, molecular interactions of the potent antitumor drug amsacrine (m-AMSA), an inhibitor of topoisomerase II, within living K562 cancer cells have been studied using surface-enhanced Raman (SER) spectroscopy. ", "It has been shown previously that DNA intercalators can inhibit the action of amsacrine and several other topoisomerase II poisons, presumably as a result of interference with the DNA binding sites for the enzyme. ", "The gadd153 promoter was strongly activated by a broad spectrum of genotoxic agents including UV-mimetic agents, DNA-cross-linking and alkylating agents, DNA intercalators, and topoisomerase inhibitors. ", "Our study indicates that Epoxy anthraquinone derivative may be a novel DNA topoisomerase inhibitor that can be potentially used for treatment of neuroblastoma or other cancer patients.", "Organic intercalators can inhibit nucleic acid synthesis in vivo, and they are now common anticancer drugs in clinical therapy. ", "Because structurally related antitumor alkaloids such as camptothecin and fagaronine are known to function as intercalative topoisomerase poisons, it is hypothesized that cytotoxic Stauranthus alkaloids may also serve as intercalative topoisomerase inhibitors.", "Specifically, we measured the ability of these compounds to 1) alter the thermal denaturation profile of DNA, 2) modify the hydrodynamic behavior of DNA, 3) inhibit the catalytic activity of purified DNA topoisomerase II in vitro, 4) promote the topoisomerase II-dependent cleavage of DNA, and 5) inhibit functions associated with DNA topoisomerase II in intact cells. Results indicated that only those analogs capable of cyclization could intercalate into DNA and inhibit topoisomerase II.", "A function for topoisomerases I and II in DNA excision repair can be postulated from the organization of the mammalian chromosome, involving nucleosomal structures and matrix-attached DNA loops. To analyse this function we determined UV-induced DNA incision in confluent human fibroblasts in the presence of 16 inhibitors of topoisomerases I and II which belonged to at least five different drug categories, based on their mechanism of action.", "In experiments to determine the mechanism of inhibition of DNA synthesis by amiloride, we observed that amiloride inhibited both the catalytic activity of purified DNA topoisomerase II in vitro and DNA topoisomerase II-dependent cell functions in vivo. Many compounds capable of inhibiting DNA topoisomerase II are DNA intercalators.", "The pyridoacridines&apos; ability to inhibit TOPO II-mediated decatenation of kDNA correlated with their cytotoxic potencies and their ability to intercalate into calf thymus DNA. These results suggest that disruption of the function of TOPO II, subsequent to intercalation, is a probable mechanism by which pyridoacridines inhibit the proliferation of HCT cells.", "Evidence for DNA intercalation by AD41 is provided by the observation that the drug introduces positive supercoils into covalently closed plasmid DNA. Based on these data, a hypothesis is proposed that would provide a general mechanism whereby intercalating agents and epipodophyllotoxins alter topoisomerase function and presumably exert their antitumor effects.", "Therefore, to more fully analyze structure-function relationships and the role of DNA binding in the action of m-AMSA, we analyzed a series of derivatives for the ability to enhance DNA cleavage mediated by human topoisomerase IIα and topoisomerase IIβ and to intercalate DNA. Results indicate that the 3&apos;-methoxy (m-AMSA) positively affects drug function, potentially by restricting the rotation of the headgroup in a favorable orientation." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/23495154", "http://www.ncbi.nlm.nih.gov/pubmed/16798938", "http://www.ncbi.nlm.nih.gov/pubmed/3002440", "http://www.ncbi.nlm.nih.gov/pubmed/8242865", "http://www.ncbi.nlm.nih.gov/pubmed/2168281", "http://www.ncbi.nlm.nih.gov/pubmed/10691026", "http://www.ncbi.nlm.nih.gov/pubmed/21591994", "http://www.ncbi.nlm.nih.gov/pubmed/7525959", "http://www.ncbi.nlm.nih.gov/pubmed/3009009", "http://www.ncbi.nlm.nih.gov/pubmed/2536704", "http://www.ncbi.nlm.nih.gov/pubmed/18043127", "http://www.ncbi.nlm.nih.gov/pubmed/19424733", "http://www.ncbi.nlm.nih.gov/pubmed/17433851", "http://www.ncbi.nlm.nih.gov/pubmed/10637356", "http://www.ncbi.nlm.nih.gov/pubmed/11077044", "http://www.ncbi.nlm.nih.gov/pubmed/17442658", "http://www.ncbi.nlm.nih.gov/pubmed/8941714", "http://www.ncbi.nlm.nih.gov/pubmed/2157558", "http://www.ncbi.nlm.nih.gov/pubmed/8449832", "http://www.ncbi.nlm.nih.gov/pubmed/2164630", "http://www.ncbi.nlm.nih.gov/pubmed/1727386", "http://www.ncbi.nlm.nih.gov/pubmed/10434060", "http://www.ncbi.nlm.nih.gov/pubmed/2695099", "http://www.ncbi.nlm.nih.gov/pubmed/22304499", "http://www.ncbi.nlm.nih.gov/pubmed/11230801", "http://www.ncbi.nlm.nih.gov/pubmed/8812219", "http://www.ncbi.nlm.nih.gov/pubmed/2845248", "http://www.ncbi.nlm.nih.gov/pubmed/22975492", "http://www.ncbi.nlm.nih.gov/pubmed/2820967", "http://www.ncbi.nlm.nih.gov/pubmed/20133050", "http://www.ncbi.nlm.nih.gov/pubmed/2537142", "http://www.ncbi.nlm.nih.gov/pubmed/367540", "http://www.ncbi.nlm.nih.gov/pubmed/21446672", "http://www.ncbi.nlm.nih.gov/pubmed/9619832" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D026942", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D059004", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D059005", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004264", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004250" ]

[ "Several targets for for miR-132 have been described and it is implicated in many diseases such as:\nneurodegenerative disease, \nepilepsy,\nschizophrenia,\nHuntington's disease (HD),\nAlzheimer's disease (AD),\nneuroinflammation,\nosteosarcoma,\nchronic lymphocytic leukemia (CLL),\nangiogenesis,\neye disease,\nalcoholic liver disease,\nprogressive supranuclear palsy (PSP taupathy),\nmild cognitive impairment." ]

[ "neurodegenerative disease", "epilepsy", "schizophrenia", "Huntington's disease (HD)", "Alzheimer's disease (AD)", "neuroinflammation", "osteosarcoma", "chronic lymphocytic leukemia (CLL)", "angiogenesis", "eye disease", "alcoholic liver disease", "progressive supranuclear palsy (PSP taupathy)", "mild cognitive impairment" ]

[ "Levels of six candidate miRNAs (miR-21, miR-199a-3p, miR-143, miR-34, miR-140, and miR-132) that were previously demonstrated to be regulated in osteosarcoma were examined in plasma of 40 osteosarcoma patients and 40 matched healthy controls by quantitative reverse-transcription polymerase chain reaction assays.", "Functional studies employing antagomirs have identified contributions from miR-34a and miR-132 to seizure-induced neuronal death whereas silencing miR-134 potently reduced status epilepticus, seizure-damage and the later occurrence of spontaneous seizures. Efforts to identify the in vivo target(s) of epilepsy-regulated miRNAs, is now a priority. Last, miRNA are stable, information-carrying (paracrine) signals. Profiling miRNA in biofluids may represent a novel source of disease biomarkers in epilepsy.", "Inflammation, stress signalling and neuronal excitation are among the pathways most impacted.", "Herpes simplex virus (HSV) causes a chronic immuno-inflammatory response in the eye that may result in corneal neovascularization during blinding immunopathological lesion stromal keratitis (SK). miR-132 is a highly conserved miRNA that is induced in endothelial cells in response to growth factors, such as vascular endothelial growth factor (VEGF).", "miR-132 expression was up-regulated (10- to 20-fold) after ocular infection with HSV, an event that involved the production of both VEGF-A and IL-17.", "The anti-angiogenic effect of antagomir-132 was reflected by a reduction in angiogenic Ras activity in corneal CD31-enriched cells (presumably blood vessel endothelial cells) during SK. To our knowledge, this is one of the first reports of miRNA involvement in an infectious ocular disease. Manipulating miRNA expression holds promise as a therapeutic approach to control an ocular lesion that is an important cause of human blindness.", "Role of miR-132 in angiogenesis", "The cyclic AMP-responsive element binding- and NMDA-regulated microRNA miR-132 was significantly down-regulated in both the schizophrenic discovery cohort and a second, independent set of schizophrenic subjects. Analysis of miR-132 target gene expression in schizophrenia gene-expression microarrays identified 26 genes up-regulated in schizophrenia subjects.", "Our data suggest miR-132 dysregulation and subsequent abnormal expression of miR-132 target genes contribute to the neurodevelopmental and neuromorphological pathologies present in schizophrenia.", "Analysis of miRNA expression profiles from sporadic progressive supranuclear palsy (PSP) patients, a major 4R-tau tauopathy, showed that miR-132 is specifically down-regulated in disease. We demonstrate that miR-132 directly targets the neuronal splicing factor polypyrimidine tract-binding protein 2 (PTBP2), which protein levels were increased in PSP patients. miR-132 overexpression or PTBP2 knockdown similarly affected endogenous 4R:3R-tau ratios in neuronal cells. Finally, we provide evidence that miR-132 is inversely correlated with PTBP2 during post-natal brain development at the time when 4R-tau becomes expressed. Taken together, these results suggest that changes in the miR-132/PTBP2 pathway could contribute to the abnormal splicing of tau exon 10 in the brain, and sheds light into the potential role played by miRNAs in a subset of tauopathies.", "Huntington's disease (HD) is a genetic neurodegenerative disease caused by abnormal CAG expansion. MicroRNAs (miRNAs) are short RNA molecules regulating gene expression, and are implicated in a variety of diseases including HD.", "Nine miRNAs (miR-22, miR-29c, miR-128, miR-132, miR-138, miR-218, miR-222, miR-344, and miR-674*) were commonly down-regulated in both the 12-month-old YAC128 and 10-week-old R6/2 mice.", "Osteosarcoma is the first primary malignant bone tumor, characterized by a complex genetic and resistance to conventional treatments.", "Osteosarcoma of rat and human origins showed a miRNA signature, which could discriminate good from bad responders. In particular, we identified five discriminating miRNAs (miR-92a, miR-99b, miR-132, miR-193a-5p and miR-422a) in patient tumors, which could be easily transferable to diagnosis.", "Levels of several microRNA (miR-10a, -10b, -212, -132, -495) were significantly altered. One of them (miR-132) has been reported to be highly inducible by growth factors and to be a key regulator of neurite outgrowth. Moreover, miR-132-recognition sequences were detected in the mRNA transcripts of two differentially expressed proteins. MicroRNA may thus represent novel biomarkers for neuronal malfunction and potential therapeutic targets for human neurodegenerative diseases.", "The data indicate that micro-RNAs encoding miR-9, miR-124a, miR-125b, miR-128, miR-132 and miR-219 are abundantly represented in fetal hippocampus, are differentially regulated in aged brain, and an alteration in specific micro-RNA complexity occurs in Alzheimer hippocampus. These data are consistent with the idea that altered micro-RNA-mediated processing of messenger RNA populations may contribute to atypical mRNA abundance and neural dysfunction in Alzheimer's disease brain." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/22659469", "http://www.ncbi.nlm.nih.gov/pubmed/23560086", "http://www.ncbi.nlm.nih.gov/pubmed/22315408", "http://www.ncbi.nlm.nih.gov/pubmed/22518321", "http://www.ncbi.nlm.nih.gov/pubmed/23001356", "http://www.ncbi.nlm.nih.gov/pubmed/21807765", "http://www.ncbi.nlm.nih.gov/pubmed/21035445", "http://www.ncbi.nlm.nih.gov/pubmed/23269581", "http://www.ncbi.nlm.nih.gov/pubmed/23485811", "http://www.ncbi.nlm.nih.gov/pubmed/20949564", "http://www.ncbi.nlm.nih.gov/pubmed/21136867", "http://www.ncbi.nlm.nih.gov/pubmed/17314675" ]

[ { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#type", "s": "http://linkedlifedata.com/resource/umls/label/A18453276", "o": "http://www.w3.org/2008/05/skos-xl#Label" }, { "p": "http://linkedlifedata.com/resource/umls/altMetaMap", "s": "http://linkedlifedata.com/resource/umls/id/C0012634", "o": "http://linkedlifedata.com/resource/umls/label/A0015570" }, { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A0015570", "o": "MeSH" }, { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#type", "s": "http://linkedlifedata.com/resource/umls/label/A17694181", "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/A7568412", "o": "http://www.w3.org/2008/05/skos-xl#Label" } ]

[ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D010300", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D007905", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004194", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D030342", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D006816", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005128", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D002908", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D020734", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D000544" ]

[ "Glutamate/aspartate transporter (GLAST) and glutamate transporter-1 (GLT-1) are the most abundant subtypes and are essential for the functioning of the mammalian CNS, but the contribution of the EAAC1 subtype in the clearance of synaptic glutamate has remained controversial, because the density of this transporter in different tissues has not been determined. Using immunofluorescence and postembedding immunogold labeling, we investigated the distributions of the glutamate-aspartate transporter (GLAST or excitatory amino acid transporter 1), vesicular glutamate transporter (VGLUT1), and the AMPA receptor glutamate receptor 4 (GluR4) along the spiral.", "To date, five distinct mammalian glutamate transporters have been cloned. The extracellular levels of excitatory amino acids are kept low by the action of the glutamate transporters. Glutamate/aspartate transporter (GLAST) and glutamate transporter-1 (GLT-1) are the most abundant subtypes and are essential for the functioning of the mammalian CNS, but the contribution of the EAAC1 subtype in the clearance of synaptic glutamate has remained controversial, because the density of this transporter in different tissues has not been determined. Expression of short interfering RNA-mediated knockdown of RTN2B decreases the EAAC1 protein level in neurons." ]

[ "EAAC1", "EAAT3", "GLT-1", "glutamate transporter-1", "excitatory amino acid transporter 1", "GLAST", "Glutamate/aspartate transporter", "GluR4", "AMPA receptor glutamate receptor 4", "VGLUT1", "vesicular glutamate transporter" ]

[ "The density of EAAC1 (EAAT3) glutamate transporters expressed by neurons in the mammalian CNS.", "Glutamate/aspartate transporter (GLAST) and glutamate transporter-1 (GLT-1) are the most abundant subtypes and are essential for the functioning of the mammalian CNS, but the contribution of the EAAC1 subtype in the clearance of synaptic glutamate has remained controversial, because the density of this transporter in different tissues has not been determined.", "Using immunofluorescence and postembedding immunogold labeling, we investigated the distributions of the glutamate-aspartate transporter (GLAST or excitatory amino acid transporter 1), vesicular glutamate transporter (VGLUT1), and the AMPA receptor glutamate receptor 4 (GluR4) along the spiral. ", "Immunogold labeling for GluR4 was confined to synaptic sites, represented by puncta in immunofluorescence. The relative numbers of puncta changed with a gradient similar to that of GLAST labeling. VGLUT1 labeling occurred in IHCs but showed no clear cochleotopic gradient. These data suggest that both the density of innervation and the activity levels of glutamatergic synapses may be involved in modulating regional expression of GLAST.", "In brain, EAAC1 (excitatory amino acid carrier 1) is the primary neuronal glutamate transporter, localized on the perisynaptic membranes that are near release sites.", "Reticulon RTN2B regulates trafficking and function of neuronal glutamate transporter EAAC1.", "Previously, we identified an EAAC1-associated protein, GTRAP3-18, an ER protein that prevents ER exit of EAAC1 when induced", "Here we show that RTN2B, a member of the reticulon protein family that mainly localizes in the ER and ER exit sites interacts with EAAC1 and GTRAP3-18", "In this study, uptake of L-[14C]cystine by three of the high affinity sodium-dependent mammalian glutamate transporters (GLT1, GLAST and EAAC1) individually expressed in HEK cells has been determined", "Reduction of L-[14C]cystine to L-[14C]cysteine in the presence of 1mM cysteinylglycine increases the uptake rate in HEK(GLT1), HEK(GLAST) and HEK(EAAC1) cells, but only a small proportion (<10%) of L-[14C]cysteine uptake in HEK(GLT1) and HEK(GLAST) cells occurs by the high affinity glutamate transporters", "Position of the third Na+ site in the aspartate transporter GltPh and the human glutamate transporter, EAAT1.", "We studied the subunit stoichiometry of two distantly related glutamate transporters, the human glial glutamate transporter hEAAT2 and a bacterial glutamate transporter from Escherichia coli, ecgltP.", "Glutamate receptors and transporters, including T1R1 and T1R3 (taste receptor 1, subtypes 1 and 3), mGluRs (metabotropic glutamate receptors), EAAC-1 (excitatory amino acid carrier-1), GLAST-1 (glutamate-aspartate transporter-1), and GLT-1 (glutamate transporter-1), are expressed in the gastrointestinal tract", "The ASCTs (alanine, serine, and cysteine transporters) belong to the solute carrier family 1 (SLC1), which also includes the human glutamate transporters (excitatory amino acid transporters, EAATs) and the prokaryotic aspartate transporter GltPh", "As astrocytes protect neurons by taking up glutamate via plasma-membrane transporters, we also studied the effect of GRK2 on the localization of the GLutamate ASpartate Transporter (GLAST)", "GLT-1, Glutamate Transporter 1, same as excitatory amino acid transporter 2; Glu, glutamate", "Multiple Functions of Glutamate Uptake via Meningococcal GltT-GltM l-Glutamate ABC Transporter in Neisseria meningitidis Internalization into Human Brain Microvascular Endothelial Cells", "Despite the high degree of amino acid sequence identity between family members, ASCTs function quite differently from the EAATs and GltPh. ", "First, Li(+) cannot support transport by EAAT2, whereas it can support transport by the other excitatory amino acid transporters, and second, EAAT2 is sensitive to a wider range of blockers than other subtypes. ", "hGLT-1 and hGLuT-1 mRNAs were most abundantly expressed in the brain, while hEAAC1 mRNA expression (3.8 kb and 2,4 kb) was strongest in peripheral organs. ", "Identification of functional domains of the human glutamate transporters EAAT1 and EAAT2.", "The glutamate transporter EAAT2 is different from other subtypes in two respects. ", "DNA methylation dependent silencing of the human glutamate transporter EAAT2 gene in glial cells.", "We have investigated the functional impact of a naturally occurring mutation of the human glutamate transporter GLT1 (EAAT2), which had been detected in a patient with sporadic amyotrophic lateral sclerosis. ", "We studied the subunit stoichiometry of two distantly related glutamate transporters, the human glial glutamate transporter hEAAT2 and a bacterial glutamate transporter from Escherichia coli, ecgltP. Using blue native polyacrylamide gel electrophoresis, analysis of concatenated transporters, and chemical cross-linking, we demonstrated that human and prokaryotic glutamate transporters expressed in Xenopus laevis oocytes or in mammalian cells are assembled as trimers composed of three identical subunits.", "Five glutamate transporters in the human brain (EAAT1-5) are present on both astroglia and neurons. We characterize the profile of three different human astroglial progenitors in vitro: human glial restricted precursors (HGRP), human astrocyte precursors (HAPC), and early-differentiated astrocytes.", "They are known to be multimers; however, the number of subunits forming a functional transporter is controversial. We studied the subunit stoichiometry of two distantly related glutamate transporters, the human glial glutamate transporter hEAAT2 and a bacterial glutamate transporter from Escherichia coli, ecgltP.", "We studied the subunit stoichiometry of two distantly related glutamate transporters, the human glial glutamate transporter hEAAT2 and a bacterial glutamate transporter from Escherichia coli, ecgltP.", "Position of the third Na+ site in the aspartate transporter GltPh and the human glutamate transporter, EAAT1.", "Immunofluorescent analysis was used to investigate the existence and location of glutamate, glutamate receptor (NR2B), and glutamate transporter (GLT1) in mouse and human sperm." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/23313319", "http://www.ncbi.nlm.nih.gov/pubmed/25196144", "http://www.ncbi.nlm.nih.gov/pubmed/14730707", "http://www.ncbi.nlm.nih.gov/pubmed/23943043", "http://www.ncbi.nlm.nih.gov/pubmed/9011758", "http://www.ncbi.nlm.nih.gov/pubmed/23393130", "http://www.ncbi.nlm.nih.gov/pubmed/18096700", "http://www.ncbi.nlm.nih.gov/pubmed/15265858", "http://www.ncbi.nlm.nih.gov/pubmed/22539860", "http://www.ncbi.nlm.nih.gov/pubmed/15863236", "http://www.ncbi.nlm.nih.gov/pubmed/26099588", "http://www.ncbi.nlm.nih.gov/pubmed/22427946", "http://www.ncbi.nlm.nih.gov/pubmed/17311293", "http://www.ncbi.nlm.nih.gov/pubmed/14662797", "http://www.ncbi.nlm.nih.gov/pubmed/14672993", "http://www.ncbi.nlm.nih.gov/pubmed/19074430", "http://www.ncbi.nlm.nih.gov/pubmed/9614067", "http://www.ncbi.nlm.nih.gov/pubmed/11031254" ]

[]

[]

[ "Sorting nexin 27 (SNX27) regulates endocytic sorting/recycling and intracellular trafficking of ion channels and receptors." ]

[]

[ "Knockdown of SNX27 by siRNA in HEK293 cells raised MRP4 expression on the plasma membrane, increased the extrusion of 6-[(14)C]mercaptopurine, an MRP4 substrate, and conferred resistance against 6-[(14)C]mercaptopurine.", "Sorting nexin 27 (SNX27) is a 62-kDa protein localized to early endosomes and known to regulate the intracellular trafficking of ion channels and receptors.", "Finally, migration assays revealed that depletion of SNX27 from HeLa and mouse principal kidney cortical collecting duct cells significantly decreases cell motility. We propose a model by which SNX27 regulates trafficking of β-Pix to focal adhesions and thereby influences cell motility.", "We found that SNX27a redirected part of 5-HT4(a)R to early endosomes.", "sorting nexin 27 (SNX27), a recently described member of a protein family involved in intracellular trafficking,", "SNX27 co-localized with transferrin receptor-positive vesicles, pointing to its participation in T cell endocytic recycling.", "This protein is a unique member of the sorting nexin family of proteins, a group generally involved in the endocytic and intracellular sorting machinery", "These previously unreported results indicate that SNX27 is a participant in NK cell polarization, as a mediator or target of the mechanism.", "Like most sorting nexins, SNX27 possesses a functional PX domain that selectively binds the membrane phospholipid phosphatidylinositol-3-phosphate (PI3P) and is important for trafficking to the early endosome.", "This is consistent with a role of SNX27 as a general regulator for sorting of membrane proteins containing a PDZ-binding motif, and its absence may alter the trafficking of these proteins, leading to growth and survival defects.", "Sorting nexin 27 (SNX27) belongs to the sorting nexin family of proteins, which participate in vesicular and protein trafficking. Similarly to all sorting nexin proteins, SNX27 has a functional PX domain that is important for endosome binding, but it is the only sorting nexin with a PDZ domain.", "These results identify SNX27 as a PDZ-containing component of the T cell immunological synapse, and demonstrate a role for this protein in the regulation of the Ras-ERK pathway, suggesting a functional relationship between SNX27 and DGKζ.", "Sorting nexins have been implicated in trafficking of proteins through endosomal compartments." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/18690037", "http://www.ncbi.nlm.nih.gov/pubmed/22411990", "http://www.ncbi.nlm.nih.gov/pubmed/23536889", "http://www.ncbi.nlm.nih.gov/pubmed/21303929", "http://www.ncbi.nlm.nih.gov/pubmed/17577583", "http://www.ncbi.nlm.nih.gov/pubmed/15466885", "http://www.ncbi.nlm.nih.gov/pubmed/21300787", "http://www.ncbi.nlm.nih.gov/pubmed/20733053", "http://www.ncbi.nlm.nih.gov/pubmed/17644068", "http://www.ncbi.nlm.nih.gov/pubmed/17828261", "http://www.ncbi.nlm.nih.gov/pubmed/21602791", "http://www.ncbi.nlm.nih.gov/pubmed/17351151", "http://www.ncbi.nlm.nih.gov/pubmed/21926430", "http://www.ncbi.nlm.nih.gov/pubmed/23524343" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D058305", "http://www.uniprot.org/uniprot/SNX27_HUMAN" ]

[ "Yes. Orphan and gene related CpG Islands follow power-law-like distributions in several genomes. The observed distributional pattern is independent of the analogous pattern that protein coding segments were reported to follow." ]

[ "yes" ]

[ "Orphan and gene related CpG Islands follow power-law-like distributions in several genomes: evidence of function-related and taxonomy-related modes of distribution.", "Here, an investigation of their distributional characteristics in a variety of genomes is undertaken for both whole CGI populations as well as for CGI subsets that lie away from known genes (gene-unrelated or \"orphan\" CGIs). In both cases power-law-like linearity in double logarithmic scale is found.", " Our results on power-law-like linearity found in orphan CGI populations suggest that the observed distributional pattern is independent of the analogous pattern that protein coding segments were reported to follow. The power-law-like patterns in the genomic distributions of CGIs described herein are found to be compatible with several other features of the composition, abundance or functional role of CGIs reported in the current literature across several genomes, on the basis of the proposed evolutionary model.", "Our results on power-law-like linearity found in orphan CGI populations suggest that the observed distributional pattern is independent of the analogous pattern that protein coding segments were reported to follow.", "The power-law-like patterns in the genomic distributions of CGIs described herein are found to be compatible with several other features of the composition, abundance or functional role of CGIs reported in the current literature across several genomes, on the basis of the proposed evolutionary model.", "Our results on power-law-like linearity found in orphan CGI populations suggest that the observed distributional pattern is independent of the analogous pattern that protein coding segments were reported to follow. ", "Our results on power-law-like linearity found in orphan CGI populations suggest that the observed distributional pattern is independent of the analogous pattern that protein coding segments were reported to follow. The power-law-like patterns in the genomic distributions of CGIs described herein are found to be compatible with several other features of the composition, abundance or functional role of CGIs reported in the current literature across several genomes, on the basis of the proposed evolutionary model.", "Initially, they were assigned the role of transcriptional regulation of protein-coding genes, especially the house-keeping ones, while more recently there is found evidence that they are involved in several other functions as well, which might include regulation of the expression of RNA genes, DNA replication etc. Here, an investigation of their distributional characteristics in a variety of genomes is undertaken for both whole CGI populations as well as for CGI subsets that lie away from known genes (gene-unrelated or \"orphan\" CGIs). In both cases power-law-like linearity in double logarithmic scale is found. ", "Our results on power-law-like linearity found in orphan CGI populations suggest that the observed distributional pattern is independent of the analogous pattern that protein coding segments were reported to follow.", "The power-law-like patterns in the genomic distributions of CGIs described herein are found to be compatible with several other features of the composition, abundance or functional role of CGIs reported in the current literature across several genomes, on the basis of the proposed evolutionary model.", "Our results on power-law-like linearity found in orphan CGI populations suggest that the observed distributional pattern is independent of the analogous pattern that protein coding segments were reported to follow." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/25242375" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D018899" ]

[ "Between 1% and 2% of human splice sites do not contain the canonical GT-AG dinucleotides" ]

[ "Between 1% and 2% " ]

[ "Of these, 98.71% contain canonical GT-AG junctions (22 199 entries) and 0.56% have non-canonical GC-AG splice site pairs. The remainder (0.73%) occurs in a lot of small groups (with a maximum size of 0.05%).", "Of these, 98.71% contain canonical dinucleotides GT and AG for donor and acceptor sites, respectively; 0.56% hold non-canonical GC-AG splice site pairs; and the remaining 0.73% occurs in a lot of small groups (with a maximum size of 0.05%). " ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/11125105", "http://www.ncbi.nlm.nih.gov/pubmed/11058137" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012326", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D015894", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004274", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D019154" ]

[ "Several staining protocols for the visualization of proteins separated by SDS-PAGE have been described in literature: \nfluorescence\nSypro Ruby\nColloidal Coomassie Blue\nCoomassie Blue\nSilver staining\nCoomassie Brilliant Blue" ]

[ "fluorochromes", "fluorescence", "Sypro Ruby", "Colloidal Coomassie Blue", "Coomassie Blue", "Silver staining", "Coomassie Brilliant Blue" ]

[ "DIGE requires the labelling of proteins by fluorochromes prior to their separation on 2DE gels. ", "Stains-All (ISA) staining method for phosphoproteins in SDS-PAGE was described.", " Pro-Q Diamond stain", "Quantitative proteome analyses suggest that the well-established stain colloidal Coomassie Blue, when used as an infrared dye, may provide sensitive, post-electrophoretic in-gel protein detection that can rival even Sypro Ruby.", "Several new fast staining protocols for the visualization of proteins separated by SDS-PAGE utilizing Coomassie Blue staining (CBS) have been described in literature. ", "The CyDye family of fluorescent dyes is currently the overwhelming choice for applications in proteomic analysis, using two-dimensional difference gel electrophoresis (2D-DIGE)", "his enables the co-detection of phosphoproteins as well as total proteins from the same gel and is accomplished by utilizing two different fluorescent stains, the ProQ-Diamond, which stains only phosphorylated proteins, and Sypro Ruby, which stains the entire subset of proteins.", "Detection of the resulting protein maps relies on staining (i.e. colloidal coomassie blue (CCB) or SYPRO Ruby (SR), in addition to many others). Fluorescent in-gel protein stains are generally preferred for higher sensitivity, reduced background, and wider dynamic range.", "Commonly used staining methods with excellent mass spectrometry compatibility are coomassie brilliant blue (CBB) or fluorescent dyes.", "The typical concentration of protein loaded varies from 0.13 to 1.40 μg/μL for a classical silver staining method in 2DE gel", "Silver staining is widely used to detect protein in polyacrylamide gels when high sensitivity is required.", "Silver staining is used to detect proteins after electrophoretic separation on polyacrylamide gels" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/24043422", "http://www.ncbi.nlm.nih.gov/pubmed/23977684", "http://www.ncbi.nlm.nih.gov/pubmed/24114871", "http://www.ncbi.nlm.nih.gov/pubmed/22665294", "http://www.ncbi.nlm.nih.gov/pubmed/22821490", "http://www.ncbi.nlm.nih.gov/pubmed/23681577", "http://www.ncbi.nlm.nih.gov/pubmed/23428344", "http://www.ncbi.nlm.nih.gov/pubmed/23256673", "http://www.ncbi.nlm.nih.gov/pubmed/23161123", "http://www.ncbi.nlm.nih.gov/pubmed/23941326", "http://www.ncbi.nlm.nih.gov/pubmed/24136520" ]

[]

[ "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=D016622", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004396", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005782" ]

[ "In the clinic, aptamers may be used to enhance the antigenicity of disseminated tumors, leading to their immune recognition and rejection; to target HPV16 E7 oncoprotein, inhibiting cell proliferation and activating apoptosis of infected cells; to act as inhibitors for targets such as VEGF, in age-related macular degeneration, and thrombin, or von Willebrand factor, in patients with acute coronary syndromes; to target the RNase H domain of the HIV-1 reverse transcriptase and inhibit viral replication; to transfect and activate B cells in human chronic lymphocytic leukemia (CLL); or finally, to be used as probes in CD4-cell phenotyping." ]

[]

[ "In murine tumor models, the aptamer-targeted siRNA-mediated NMD inhibition in tumor cells led to significant inhibition of tumor growth, which was superior to best-in-class \"conventional\" cancer vaccination protocols. Tumor-targeted NMD inhibition forms the basis of a simple, broadly useful, and clinically feasible approach to enhance the antigenicity of disseminated tumors leading to their immune recognition and rejection.", "This study is focused on one aptamer (termed A2). Transfection of this molecule into HPV16-transformed cells resulted in inhibition of cell proliferation (shown using real-time cell electronic sensing and MTT assays) due to the induction of apoptosis (as demonstrated by Annexin V/propidium iodide staining).", "Transfection of cells with A2 was correlated with the loss of E7 and the induction of apoptosis.", "Aptamers specific for a number of cellular and viral proteins have been documented previously; one aptamer (Macugen) is approved for clinical use and several others are in clinical trials.", "The high binding affinity and specificity of aptamers allows for isolation of an artificial ligand for theoretically any therapeutic target of interest.", "Aptamers are a special class of nucleic acid molecules that are beginning to be investigated for clinical use. These small RNA/DNA molecules can form secondary and tertiary structures capable of specifically binding proteins or other cellular targets; they are essentially a chemical equivalent of antibodies. Aptamers have the advantage of being highly specific, relatively small in size, and non-immunogenic.", "In the last two decades, many aptamers have been clinically developed as inhibitors for targets such as vascular endothelial growth factor (VEGF) and thrombin.", "The first aptamer based therapeutic was FDA approved in 2004 for the treatment of age-related macular degeneration and several other aptamers are currently being evaluated in clinical trials.", "Preclinical studies using aptamer-siRNA chimeras and aptamer targeted nanoparticle therapeutics have been very successful in mouse models of cancer and HIV.", "In summary aptamers are in several stages of development, from pre-clinical studies to clinical trials and even as FDA approved therapeutics.", "In subcutaneous and metastatic tumour models, tumour-targeted delivery of NMD factor-specific siRNAs conjugated to oligonucleotide aptamer ligands led to significant inhibition of tumour growth that was superior to that of vaccination with granulocyte-macrophage colony-stimulating factor (GM-CSF)-expressing irradiated tumour cells, and could be further enhanced by co-stimulation.", "An assortment of non-viral carriers including liposomes, peptides, polymers, and aptamers are being evaluated for their ability to shepherd siRNA to the target tissue and cross the plasma membrane barrier into the cell.", "In addition, a new thromboxane receptor antagonist, NCX-4016, a newly discovered protease-activated receptor antagonist that targets thrombin-induced platelet aggregation, and anti-von Willebrand factor aptamers show tremendous promise in refining antiplatelet therapy by targeting different receptors and molecules.", "First-in-human evaluation of anti von Willebrand factor therapeutic aptamer ARC1779 in healthy volunteers", "ARC1779 is a therapeutic aptamer antagonist of the A1 domain of von Willebrand Factor (vWF), the ligand for receptor glycoprotein 1b on platelets. ARC1779 is being developed as a novel antithrombotic agent for use in patients with acute coronary syndromes.", "This is the first-in-human evaluation of a novel aptamer antagonist of vWF. ARC1779 produced dose- and concentration-dependent inhibition of vWF activity and platelet function with duration of effect suitable for the intended clinical use in acute coronary syndromes.", "Wet age-related macular degeneration and diabetic retinopathy are pathological consequences of vascular endothelial growth factor (VEGF) release as a reaction to deficiency of oxygen and nutrients in the macular cells.", "FDA recently approved two drugs specifically aimed at VEGF, bevacizumab, a humanized monoclonal antibody, and pegaptinib, a pegylated aptamer with application in ophthalmic pathologies.", "Delivery of double-stranded DNA thioaptamers into HIV-1 infected cells for antiviral activity", "Our lead thioaptamer, R12-2, targets the RNase H domain of the HIV-1 reverse transcriptase (RT) and inhibits viral infection in U373-MAGI-CCR5 cells.", "In this report, we demonstrate that monothioate-modified DNA duplex oligonucleotides can be efficiently delivered into cells by liposome-based transfection agents to inhibit HIV replication.", "Nucleic acid aptamers in therapeutic anticoagulation", "Pegaptanib sodium for the treatment of neovascular age-related macular degeneration", "Pegaptanib sodium is one of the first therapeutics belonging to the class of compounds known as aptamers.", "The article highlights and summarises the results of the multi-centre, randomised, sham-controlled clinical trials with pegaptanib sodium to treat subfoveal choroidal neovascularisation in AMD. In addition, the safety profile is reviewed.", "Regulatable aptamers in medicine: focus on antithrombotic strategies", "After a decade of intensive research, technology development and initial clinical evaluation, aptamers have now demonstrated broad potential as direct protein ligands and inhibitors, and thus represent an exciting class of compounds for the development of new therapeutic and diagnostic agents. ", "Two R-aptamers (R10-60 and D-R15-8) with the predominant shared characteristics were selected for further study on primary human chronic lymphocytic leukemia (CLL) B cells, which are well known to be difficult to transfect and activate.", "Together, these findings suggest that the sequence compositions in R-aptamers that promote multimerization and contain optimal ISS CpG motifs facilitate the delivery of ISS-ODN to CLL cells and enhance the activation of these cells.", "In particular, the use of aptamers for the alleviation of blood clotting and the treatment of AIDS are considered.", "We synthesized an RNA aptamer probe specific for human CD4 using a reported sequence and investigated the potential use of this probe in cell phenotyping. Studies in cultured cells demonstrated that the synthetic CD4 aptamer had a nearly identical cell-binding specificity as the standard CD4 antibody. Fluorescent microscopy confirmed that the aptamer and antibody generated the same CD4 staining pattern in cells without competing with one another.", "transfection of HPV16-transformed cells with A2 appeared to result in the loss of E7 and rise in pRb levels" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/18708826", "http://www.ncbi.nlm.nih.gov/pubmed/18025536", "http://www.ncbi.nlm.nih.gov/pubmed/23738000", "http://www.ncbi.nlm.nih.gov/pubmed/15968382", "http://www.ncbi.nlm.nih.gov/pubmed/16631118", "http://www.ncbi.nlm.nih.gov/pubmed/9704089", "http://www.ncbi.nlm.nih.gov/pubmed/20855639", "http://www.ncbi.nlm.nih.gov/pubmed/20161621", "http://www.ncbi.nlm.nih.gov/pubmed/21838685", "http://www.ncbi.nlm.nih.gov/pubmed/24198064", "http://www.ncbi.nlm.nih.gov/pubmed/17951900", "http://www.ncbi.nlm.nih.gov/pubmed/16842232", "http://www.ncbi.nlm.nih.gov/pubmed/22352726", "http://www.ncbi.nlm.nih.gov/pubmed/20463739", "http://www.ncbi.nlm.nih.gov/pubmed/15926872", "http://www.ncbi.nlm.nih.gov/pubmed/15461575", "http://www.ncbi.nlm.nih.gov/pubmed/12828856" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D045506", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D052157", "http://www.biosemantics.org/jochem#4265428", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D052158" ]

[ "Panama disease of banana is caused by the fungus Fusarium oxysporum f. sp. cubense." ]

[ "Fusarium oxysporum f. sp. cubense" ]

[ "Fusarium oxysporum f. sp. cubense (Foc), the causal agent of Fusarium wilt (Panama disease), is one of the most devastating diseases of banana (Musa spp.)", "avendish, the most widely grown banana cultivar, is relatively resistant to Race 1 of Fusarium oxysporum f. sp. cubense (Foc1) which caused widespread Panama disease during the first half of the 20th century but is susceptible to Tropical Race 4 of Foc (Foc TR4) which is threatening world banana production. ", "Fusarium oxysporum f. sp. cubense race 4 (FOC), the causal agent of Panama disease in banana,", "Fusarium oxysporum f.sp. cubense, a causative agent of Panama disease", "Fusarium wilt of banana (also known as Panama disease) is caused by Fusarium oxysporum f. sp. cubense", " inoculated with Fusarium oxysporum f.sp. cubense (FOC), Race 4, the causal agent of Panama disease", "the fungus causing Panama disease of banana", "Panama disease of banana, caused by the fungus Fusarium oxysporum f. sp. cubense, is a serious constraint both to the commercial production of banana and cultivation for subsistence agriculture" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/24304681", "http://www.ncbi.nlm.nih.gov/pubmed/18943184", "http://www.ncbi.nlm.nih.gov/pubmed/12926878", "http://www.ncbi.nlm.nih.gov/pubmed/25969777", "http://www.ncbi.nlm.nih.gov/pubmed/9482835", "http://www.ncbi.nlm.nih.gov/pubmed/24376590", "http://www.ncbi.nlm.nih.gov/pubmed/23355016" ]

[ { "p": "http://purl.uniprot.org/core/reviewed", "s": "http://purl.uniprot.org/taxonomy/5507", "o": "true" }, { "p": "http://purl.uniprot.org/core/otherName", "s": "http://purl.uniprot.org/taxonomy/5507", "o": "fungal sp. ZZF51" }, { "p": "http://purl.uniprot.org/core/commonName", "s": "http://purl.uniprot.org/taxonomy/5507", "o": "Panama disease fungus" }, { "p": "http://purl.uniprot.org/core/scientificName", "s": "http://purl.uniprot.org/taxonomy/5507", "o": "Fusarium oxysporum" }, { "p": "http://purl.uniprot.org/core/mnemonic", "s": "http://purl.uniprot.org/taxonomy/5507", "o": "FUSOX" }, { "p": "http://www.w3.org/2000/01/rdf-schema#subClassOf", "s": "http://purl.uniprot.org/taxonomy/660034", "o": "http://purl.uniprot.org/taxonomy/5507" }, { "p": "http://purl.uniprot.org/core/scientificName", "s": "http://purl.uniprot.org/taxonomy/660034", "o": "Fusarium oxysporum II5" }, { "p": "http://www.w3.org/2000/01/rdf-schema#subClassOf", "s": "http://purl.uniprot.org/taxonomy/909454", "o": "http://purl.uniprot.org/taxonomy/5507" }, { "p": "http://purl.uniprot.org/core/scientificName", "s": "http://purl.uniprot.org/taxonomy/909454", "o": "Fusarium oxysporum Cotton" }, { "p": "http://www.w3.org/2000/01/rdf-schema#subClassOf", "s": "http://purl.uniprot.org/taxonomy/660031", "o": "http://purl.uniprot.org/taxonomy/5507" }, { "p": "http://purl.uniprot.org/core/scientificName", "s": "http://purl.uniprot.org/taxonomy/660031", "o": "Fusarium oxysporum PHW808" }, { "p": "http://purl.uniprot.org/core/strain", "s": "http://purl.uniprot.org/taxonomy/5507", "o": "http://linkedlifedata.com/resource/#_2503" }, { "p": "http://purl.uniprot.org/core/name", "s": "http://linkedlifedata.com/resource/#_2503", "o": "FOM24" } ]

[ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=diseases_category", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D010176", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D010935" ]

[ "Nalmefene shows opioid receptor antagonism, binds the μ-opioid receptor (MOR1) and modulates opioidergic transmission in the CNS." ]

[]

[ "Opioids that stimulate the μ-opioid receptor (MOR1) are the most frequently prescribed and effective analgesics. Here we present a structural model of MOR1. Molecular dynamics simulations show a ligand-dependent increase in the conformational flexibility of the third intracellular loop that couples with the G protein complex. These simulations likewise identified residues that form frequent contacts with ligands. We validated the binding residues using site-directed mutagenesis coupled with radioligand binding and functional assays. The model was used to blindly screen a library of ∼1.2 million compounds. From the 34 compounds predicted to be strong binders, the top three candidates were examined using biochemical assays. One compound showed high efficacy and potency. Post hoc testing revealed this compound to be nalmefene, a potent clinically used antagonist, thus further validating the model. ", "The neurobiological mechanism by which opioid modulators affect drinking behavior is based on the strong connection between the endogenous opioid system, the dopamine system and the influence of the CNS stress response.", "Naltrexone- and to a lesser extent nalmefene- is an agent that modulates opioidergic transmission in the CNS and it shows a limited but well-studied efficacy in treating alcohol dependence. ", "Several derivatives of Naltrexone, Nalmefene (Nal) and JKB-119, exert immunomodulatory activity; however, unlike Nal, JKB-119 does not show significant opioid receptor antagonism. " ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/22078567", "http://www.ncbi.nlm.nih.gov/pubmed/21651459", "http://www.ncbi.nlm.nih.gov/pubmed/21291870" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D045504", "http://www.biosemantics.org/jochem#4258016", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D040542" ]

[ "Synostosis of sagittal and lambdoid structures are characteristic to the Mercedes Benz syndrome." ]

[ "sagittal", "lambdoid" ]

[ "Among these are a trisutural fusion, dubbed the \"Mercedes Benz pattern,\" involving the sagittal and both lambdoid sutures. ", "CONCLUSIONS: Despite fusion of the sagittal suture, the surgical treatment for Mercedes Benz pattern craniosynostosis should include skull lengthening, not reduction.", "Multisutural craniosynostosis that includes bilateral lambdoid and sagittal synostosis (BLSS) results in a very characteristic head shape with frontal bossing, turribrachycephaly, biparietal narrowing, occipital concavity, and inferior displacement of the ears. This entity has been reported both in the genetics literature as craniofacial dyssynostosis and in the surgical literature as \"Mercedes Benz\" syndrome. ", "Bilambdoid and posterior sagittal synostosis: the Mercedes Benz syndrome.", "A consistent pattern of craniosynostosis in the sagittal and bilateral lambdoid sutures is described in three patients. The external cranial ridging associated with fusion of these sutures produces a characteristic triradiate, or \"Mercedes Benz,\" appearance to the posterior skull.", "Bilambdoid and posterior sagittal synostosis: the Mercedes Benz syndrome." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/20048621", "http://www.ncbi.nlm.nih.gov/pubmed/19396832", "http://www.ncbi.nlm.nih.gov/pubmed/9780908" ]

[]

[ "http://www.disease-ontology.org/api/metadata/DOID:11971", "http://www.disease-ontology.org/api/metadata/DOID:2340", "http://www.disease-ontology.org/api/metadata/DOID:225" ]

[ "Yes, valproic acid canact as an activator of AMPK.", "VPA is a novel activator of AMP-activated protein kinase (AMPK)" ]

[ "yes" ]

[ "Here we demonstrate that VPA is a novel activator of AMP-activated protein kinase (AMPK), a key regulator of cellular metabolism, using primary mouse and human hepatocytes.", "These studies are the first to establish VPA and its metabolites as in vitro activators of AMPK." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/24105977", "http://www.ncbi.nlm.nih.gov/pubmed/23889921" ]

[]

[ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0031588", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D055372", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0004679", "http://www.uniprot.org/uniprot/AAKB1_HUMAN", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:2000479", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D014635", "http://www.biosemantics.org/jochem#4271063", "http://www.uniprot.org/uniprot/AAPK2_HUMAN" ]

[ "Medulloblastoma comprises approximately 20% of all primary pediatric brain tumors. Multiple signaling pathways have been associated with disease formation and growth. These include the developmental pathways Hedgehog, Notch, and Wnt, as well as pathways in which the receptor tyrosine kinases (RTK) c-Met, erbB2, IGF-R and TrkC, and the oncoprotein Myc are involved." ]

[ "Hedgehog", "Notch", "Wnt", "c-Met", "erbB2", "IGF-R", "TrkC", "Myc" ]

[ "Hedgehog (Hh) signaling is an important factor in growth and patterning during embryonic development. A mutation in Patched, Smoothened or Gli1, which regulate the Hh signaling pathway, might lead to the onset of glioblastoma, basal cell carcinoma, medulloblastoma and rhabdomyosarcoma", "These data indicate that inhibition of Aurora Kinase A inhibits cell growth in medulloblastoma through inhibition of pro-proliferative signaling pathways Wnt, Myc, and RB", "Multiple signaling pathways have been associated with medulloblastoma formation and growth. These include the developmental pathways Hedgehog, (Hh) Notch, and Wnt as well as the receptor tyrosine kinases (RTK) c-Met, erbB2, IGF-R and TrkC, and the oncoprotein Myc", "Activation of neurotrophin-3 receptor TrkC induces apoptosis in medulloblastomas", "Elevated expression of the neurotrophin-3 (NT-3) receptor TrkC by childhood medulloblastomas is associated with favorable clinical outcome", "Considered collectively, these results support the conclusion that the biological actions of TrkC activation affect medulloblastoma outcome by inhibiting tumor growth through the promotion of apoptosis.", "During development, proliferation of cerebellar granule neuron precursors (CGNP), candidate cells-of-origin for the pediatric brain tumor medulloblastoma, requires signaling by Sonic hedgehog (Shh) and insulin-like growth factor (IGF), the pathways of which are also implicated in medulloblastoma.", "Sonic hedgehog and insulin-like growth factor signaling synergize to induce medulloblastoma formation from nestin-expressing neural progenitors in mice.", "Ectopic expression of alpha and beta interferons in the developing brain also induces Shh-mediated medulloblastoma formation, suggesting a possible role for antiviral response in the genesis of medulloblastoma.", "Aberrant activation of the Hedgehog (Hh) and Wnt developmental pathways is associated with medulloblastoma, but deregulation of other molecular pathways, including insulin-like growth factor (IGF) signaling, has also been implicated in the pathogenesis of the tumor.", "Sunitinib induces apoptosis and growth arrest of medulloblastoma tumor cells by inhibiting STAT3 and AKT signaling pathways.", "Aberrant activation of the Sonic hedgehog (Shh) and insulin-like growth factor (IGF) pathways is associated with human medulloblastomas.", "N-myc can substitute for insulin-like growth factor signaling in a mouse model of sonic hedgehog-induced medulloblastoma.", "Aberrant activation of the Hedgehog (Hh) and Wnt developmental pathways is associated with medulloblastoma, but deregulation of other molecular pathways, including insulin-like growth factor (IGF) signaling, has also been implicated in the pathogenesis of the tumor", "Aberrant expression/activation of EGFR is found in multiple human cancers, including medulloblastoma, the most prevalent pediatric brain cancer, and often has been associated with metastasis, poor prognosis, and resistance to chemotherapy", "We emphasize the cancer-relevance of cilia-dependent signaling pathways and proteins including mTOR, VHL, TSC, WNT, Aurora-A, NEDD9, and Hedgehog, and highlight the emerging role of ciliary dysfunction in renal cell carcinoma, medulloblastoma, and breast cancer", "Here, we show that in medulloblastoma cells, both EGF and ouabain activate Erk1/2 and PI3K/Akt signaling", "Expression level of tumor/metastasis suppressive miRNAs in the WNT signaling associated medulloblastomas is likely to determine their response to treatment, and thus, these miRNAs would be important biomarkers for risk stratification within the WNT signaling associated medulloblastomas.", "Aberrant activation of the Sonic hedgehog (Shh) and insulin-like growth factor (IGF) pathways is associated with human medulloblastomas", "Shh-dependent medulloblastoma formation is enhanced by hyperactive insulin-like growth factor (IGF) signaling and ectopic expression of Myc oncogenes", "Phosphatidylinositol 3'-kinase/AKT signaling is activated in medulloblastoma cell proliferation and is associated with reduced expression of PTEN.", "A number of miRNAs like miR-193a, miR-224/miR-452 cluster, miR-182/miR-183/miR-96 cluster, and miR-148a having potential tumor/metastasis suppressive activity were found to be overexpressed in the WNT signaling associated medulloblastomas", "The requirement for SHH-Gli signaling in the growth of the mouse brain, together with the ability of inappropriate pathway activation in the cerebellum to cause medulloblastomas, and the inhibition of the growth of a number of brain tumors with cyclopamine, a SHH signaling inhibitor, underscores the critical role of the SHH-GLI pathway in brain growth and tumor formation", "Aberrant activation of the Hedgehog (Hh) and Wnt developmental pathways is associated with medulloblastoma, but deregulation of other molecular pathways, including insulin-like growth factor (IGF) signaling, has also been implicated in the pathogenesis of the tumor", "Distinctive microRNA signature of medulloblastomas associated with the WNT signaling pathway." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/21679342", "http://www.ncbi.nlm.nih.gov/pubmed/20232424", "http://www.ncbi.nlm.nih.gov/pubmed/16510586", "http://www.ncbi.nlm.nih.gov/pubmed/24982684", "http://www.ncbi.nlm.nih.gov/pubmed/18651559", "http://www.ncbi.nlm.nih.gov/pubmed/9973222", "http://www.ncbi.nlm.nih.gov/pubmed/19738049", "http://www.ncbi.nlm.nih.gov/pubmed/16707597", "http://www.ncbi.nlm.nih.gov/pubmed/20053726", "http://www.ncbi.nlm.nih.gov/pubmed/15013214", "http://www.ncbi.nlm.nih.gov/pubmed/17545597", "http://www.ncbi.nlm.nih.gov/pubmed/21358093", "http://www.ncbi.nlm.nih.gov/pubmed/19747111" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D015398", "http://www.disease-ontology.org/api/metadata/DOID:3858", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0009966" ]

[ "In a process of epithelial-mesenchymal transition (EMT), besides changing their adhesive repertoire, cancer cells employ developmental processes to gain migratory and invasive properties that involve a dramatic reorganization of the actin cytoskeleton and the concomitant formation of membrane protrusions required for invasive growth. An important type of such membrane protrusions are the invadopodia, which have been increasingly recognized as important drivers of local invasion in metastasis. They are basally-localized, actin-rich structures that concentrate protease activity to areas of the cell in contact with the extracellular matrix." ]

[]

[ "FHOD1, a poorly studied formin, appeared to be markedly upregulated upon EMT.", "Furthermore, functional assays demonstrated that FHOD1 contributes to cell migration and invasion. Finally, FHOD1 depletion reduced the ability of EMT cancer cells to form invadopodia and to degrade extracellular matrix. Our results indicate that FHOD1 participates in cytoskeletal changes in EMT.", "Invadopodia are considered to be crucial structures that allow cancer cells to penetrate across the extracellular matrix (ECM) by using matrix metalloproteinases (MMPs).", "Previously, we isolated a highly invasive A431-III subline from parental A431 cells by Boyden chamber assay. The A431-III cells possess higher invasive and migratory abilities, elevated levels of MMP-9 and an enhanced epithelial-mesenchymal transition (EMT) phenotype. In this study, we discovered that A431-III cells had an increased potential to form invadopodia and an improved capacity to degrade ECM compared with the original A431 cells.", "Activated Twist upregulates N-cadherin and downregulates E-cadherin, which are the hallmarks of EMT. Moreover, Twist plays an important role in some physiological processes involved in metastasis, like angiogenesis, invadopodia, extravasation, and chromosomal instability.", "Transforming growth factor β (TGF-β)-stimulated epithelial-mesenchymal transition (EMT) is an important developmental process that has also been implicated in increased cell invasion and metastatic potential of cancer cells.", "Herein, we demonstrate that TGF-β-induced Hic-5 up-regulation or ectopic expression of Hic-5 in normal MCF10A cells promoted increased extracellular matrix degradation and invasion through the formation of invadopodia.", "These data identify Hic-5 as a critical mediator of TGF-β-stimulated invadopodia formation, cell migration, and invasion.", "Recently, invadopodia have been increasingly recognized as important drivers of local invasion in metastasis. Invadopodia are basally-localized, actin-rich structures that concentrate protease activity to areas of the cell in contact with the extracellular matrix. We recently found that the transcription factor Twist1, a central regulator of the epithelial-mesenchymal transition (EMT), promotes invadopodia formation via upregulation of platelet-derived growth factor receptor (PDGFR) expression and activity.", "Twist1-induced invadopodia formation promotes tumor metastasis", "The Twist1 transcription factor is known to promote tumor metastasis and induce Epithelial-Mesenchymal Transition (EMT). Here, we report that Twist1 is capable of promoting the formation of invadopodia, specialized membrane protrusions for extracellular matrix degradation.", "Twist1 induces PDGFRα expression, which in turn activates Src, to promote invadopodia formation. We show that Twist1 and PDGFRα are central mediators of invadopodia formation in response to various EMT-inducing signals.", "Podosome-like structures of non-invasive carcinoma cells are replaced in epithelial-mesenchymal transition by actin comet-embedded invadopodia", "Podosomes and invadopodia are actin-based structures at the ventral cell membrane, which have a role in cell adhesion, migration and invasion.", "In conclusion, EMT affects the invasion machinery of oral squamous carcinoma cells. Non-invasive squamous carcinoma cells constitutively organize podosomes, whereas invasive cells form invadopodia. The club-ended cell extensions, or externalized invadopodia, are involved in ECM degradation and maintenance of contact to adhesion substrate and surrounding cells during invasion.", "In a process of epithelial-mesenchymal transition (EMT), besides changing their adhesive repertoire, cancer cells employ developmental processes to gain migratory and invasive properties that involve a dramatic reorganization of the actin cytoskeleton and the concomitant formation of membrane protrusions required for invasive growth. The molecular processes underlying such cellular changes are still only poorly understood, and the various migratory organelles, including lamellipodia, filopodia, invadopodia and podosomes, still require a better functional and molecular characterization." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/23873099", "http://www.ncbi.nlm.nih.gov/pubmed/24086398", "http://www.ncbi.nlm.nih.gov/pubmed/21725138", "http://www.ncbi.nlm.nih.gov/pubmed/19169796", "http://www.ncbi.nlm.nih.gov/pubmed/21397860", "http://www.ncbi.nlm.nih.gov/pubmed/22529104", "http://www.ncbi.nlm.nih.gov/pubmed/19656240", "http://www.ncbi.nlm.nih.gov/pubmed/23991004" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D058750", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0001837" ]

[ "Recent sequencing and resequencing (i.e., polymorphism identification) efforts have catalyzed the quest for 'driver' mutations (i.e., those genetic alterations which contribute to the transformation of a normal cell to a proliferating cancerous cell) in distinction to 'passenger' mutations which reflect mutations that merely build up in course of normal and unchecked (i.e., cancerous) somatic cell replication and proliferation. Analysis of the frequency of specific mutations across different tumors has been able to identify some, but not all of the mutated genes that contribute to tumor initiation and progression. A subset of these mutations contribute to tumor progression (known as \"driver\" mutations) whereas the majority of these mutations are effectively neutral (known as \"passenger\" mutations)." ]

[]

[ "We constructed DriverDB (http://ngs.ym.edu.tw/driverdb/), a database which incorporates 6079 cases of exome-seq data, annotation databases (such as dbSNP, 1000 Genome and Cosmic) and published bioinformatics algorithms dedicated to driver gene/mutation identification.", "DriverDB: an exome sequencing database for cancer driver gene identification.", "With the ability to fully sequence tumor genomes/exomes, the quest for cancer driver genes can now be undertaken in an unbiased manner.", "Here we show that the combination of complementary methods allows identifying a comprehensive and reliable list of cancer driver genes. ", "In summary, the catalog of driver genes and the methodology presented here open new avenues to better understand the mechanisms of tumorigenesis.", "A subset of these mutations contribute to tumor progression (known as \"driver\" mutations) whereas the majority of these mutations are effectively neutral (known as \"passenger\" mutations)", "The ability to differentiate between drivers and passengers will be critical to the success of upcoming large-scale cancer DNA resequencing projects.", " In fact, recent sequencing and resequencing (i.e., polymorphism identification) efforts have catalyzed the quest for protein kinase 'driver' mutations (i.e., those genetic alterations which contribute to the transformation of a normal cell to a proliferating cancerous cell) in distinction to kinase 'passenger' mutations which reflect mutations that merely build up in course of normal and unchecked (i.e., cancerous) somatic cell replication and proliferation.", "This method was applied to available breast cancer, colorectal cancer, and glioblastoma sequence data, and identified Wnt/TGF-beta cross-talk, Wnt/VEGF signaling, and MAPK/focal adhesion kinase pathways as targets of rare driver mutations in breast, colorectal cancer, and glioblastoma, respectively.", "Analysis of the frequency of specific mutations across different tumors has been able to identify some, but not all of the mutated genes that contribute to tumor initiation and progression.", "We are developing a cross-species comparison strategy to distinguish between cancer driver- and passenger gene alteration candidates, by utilizing the difference in genomic location of orthologous genes between the human and other mammals.", "Major tumor sequencing projects have been conducted in the past few years to identify genes that contain 'driver' somatic mutations in tumor samples.", "At the same time, we determined that some genes previously reported as drivers were not significant by the new analysis because mutations in these genes occurred mainly in tumors with large background mutation rates. ", "Identifying genomic alterations driving breast cancer is complicated by tumor diversity and genetic heterogeneity.", "Herein we report a proof-of-principle study illustrating a novel dog-human comparison strategy that addresses a central aim of cancer research, namely cancer driver-passenger distinction.", "Expansion of this study would make more driver-passenger distinctions for cancers with large genomic amplifications or deletions, and address key questions regarding the relationship between cancer pathogenesis and epithelial cell polarity control in mammals.", "Adjusting for background mutation frequency biases improves the identification of cancer driver genes.", "The identification of cancer drivers is a major goal of current cancer research", "We conclude that zebrafish-human comparative analysis represents a powerful, and broadly applicable, tool to enrich for evolutionarily conserved cancer drivers." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/23416983", "http://www.ncbi.nlm.nih.gov/pubmed/24009526", "http://www.ncbi.nlm.nih.gov/pubmed/24233780", "http://www.ncbi.nlm.nih.gov/pubmed/20707908", "http://www.ncbi.nlm.nih.gov/pubmed/22851646", "http://www.ncbi.nlm.nih.gov/pubmed/21169372", "http://www.ncbi.nlm.nih.gov/pubmed/24084849", "http://www.ncbi.nlm.nih.gov/pubmed/19081671", "http://www.ncbi.nlm.nih.gov/pubmed/24214964", "http://www.ncbi.nlm.nih.gov/pubmed/23694700", "http://www.ncbi.nlm.nih.gov/pubmed/18339846", "http://www.ncbi.nlm.nih.gov/pubmed/19574499" ]

[]

[ "http://www.disease-ontology.org/api/metadata/DOID:162", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009369", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D052138" ]

[ "A naked mtDNA molecule is longer than a typical mitochondrion and is therefore compacted in vivo to form a nucleoprotein complex, denoted the mitochondrial nucleoid." ]

[]

[ "A naked mtDNA molecule is longer than a typical mitochondrion and is therefore compacted in vivo to form a nucleoprotein complex, denoted the mitochondrial nucleoid.", "The packaging of mitochondrial DNA (mtDNA) into DNA-protein assemblies called nucleoids provides an efficient segregating unit of mtDNA,", "Mitochondrial DNA (mtDNA) is organized in nucleoids in complex with accessory proteins, proteins of mtDNA replication and gene expression machinery.", "The independent mitochondrial genetic information is organized in so-called mitochondrial nucleoids", " packaging of mitochondrial DNA (mtDNA) into protein-DNA assemblies called nucleoids confers higher-order organization to the mitochondrial genome.", "mitochondrial DNA is packaged into macromolecular assemblies called nucleoids, composed of one or more copies of mitochondrial DNA and associated proteins. ", "human mitochondrial DNA (mtDNA) had long been believed to be rather naked because mitochondria lack histone" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/23637282", "http://www.ncbi.nlm.nih.gov/pubmed/19703654", "http://www.ncbi.nlm.nih.gov/pubmed/23721879", "http://www.ncbi.nlm.nih.gov/pubmed/23220174", "http://www.ncbi.nlm.nih.gov/pubmed/19704786", "http://www.ncbi.nlm.nih.gov/pubmed/20577028", "http://www.ncbi.nlm.nih.gov/pubmed/15126284" ]

[]

[ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0042645", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0090144", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0009295", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D024101", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0090143" ]

[ "Treatment of amiodarone-induced thyrotoxicosis is complex and may include drugs such as antithyroid drugs, beta-blockers, corticosteroids lithium as well as iopanoic acid in preparation of thyroidectomy. Total thyroidectomy and radioiodine represent alternative treatment options" ]

[]

[ "Prednisone remains the preferred treatment modality of AIT type 2, because perchlorate given alone or in combination with prednisone had no better outcomes.", "Total thyroidectomy, by rapidly restoring euthyroidism, may improve cardiac function and reduce the risk of mortality in AIT patients with severe LV dysfunction.", "Prednisone restores euthyroidism in most type 2 AIT patients, irrespective of amiodarone continuation or withdrawal. However, continuing amiodarone increases the recurrence rate of thyrotoxicosis, causing a delay in the stable restoration of euthyroidism and a longer exposure of the heart to thyroid hormone excess.", "Steroid therapy should be started when findings indicate type II or mixed-type AIT. Beta blockers may prevent heart thyrotoxicosis and recurrence of primary arrhythmia if amiodarone is discontinued.", "Glucocorticoids are the first-line treatment in type 2 AIT, whereas thionamides play no role in this destructive thyroiditis.", "iopanoic can be used to rapidly lower FT(3) levels and to treat symptoms of thyrotoxicosis in a preoperative setting.", "The patient responded to iopanoic acid with a rapid decrease in his FT(3) level and slight increase in his FT(4) level.", "In patients with type-2 AIT, RAI treatment may be the therapy of choice for thyroid gland ablation.", "In type 1 AIT thionamides represent the treatment of choice for North Americans as well as for Europeans,", "Glucocorticoids are the selected treatment for type 2 AIT, alone (62%vs. 46% in Europe, P < 0.05) or in association with thionamides", "After restoration of euthyroidism, thyroid ablation in the absence of recurrent thyrotoxicosis is recommended in type 1 AIT less frequently by North Americans." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/22130792", "http://www.ncbi.nlm.nih.gov/pubmed/19109209", "http://www.ncbi.nlm.nih.gov/pubmed/20583541", "http://www.ncbi.nlm.nih.gov/pubmed/19105148", "http://www.ncbi.nlm.nih.gov/pubmed/22386340", "http://www.ncbi.nlm.nih.gov/pubmed/19675515", "http://www.ncbi.nlm.nih.gov/pubmed/18410546", "http://www.ncbi.nlm.nih.gov/pubmed/21865355", "http://www.ncbi.nlm.nih.gov/pubmed/22865896", "http://www.ncbi.nlm.nih.gov/pubmed/21225109", "http://www.ncbi.nlm.nih.gov/pubmed/18595575", "http://www.ncbi.nlm.nih.gov/pubmed/18421194", "http://www.ncbi.nlm.nih.gov/pubmed/19622616" ]

[]

[]

[ "Exercise has been shown to increase TRβ1 receptor expression in young rats. Exercise has been shown to increase both TRα1 and TRβ1 receptor expression in aged rats." ]

[]

[ "Exercise increased the TRβ1 receptor, L-channel and NCX", "Expression of TR-alpha1 and TR-beta1 proteins in the heart were significantly lower in sedentary aged rats than in sedentary young rats and were significantly higher in trained aged rats than in sedentary aged rats.", "Myocyte TRbeta1 was upregulated in models with a hyperthyroid-like phenotype, TH (triiodothyronine, T3), in culture and exercise in vivo." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/11577024", "http://www.ncbi.nlm.nih.gov/pubmed/14704232", "http://www.ncbi.nlm.nih.gov/pubmed/21625820" ]

[]

[ "http://www.uniprot.org/uniprot/THAB_PAROL", "http://www.uniprot.org/uniprot/THA_LITCT", "http://www.uniprot.org/uniprot/THAB_XENLA", "http://www.uniprot.org/uniprot/THB_SHEEP", "http://www.uniprot.org/uniprot/THA_MOUSE", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0046966", "http://www.uniprot.org/uniprot/THAA_PAROL", "http://www.uniprot.org/uniprot/THA_PYGAD", "http://www.uniprot.org/uniprot/THA_CHICK", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013963", "http://www.uniprot.org/uniprot/THA_APTPA", "http://www.uniprot.org/uniprot/THB_LITCT", "http://www.uniprot.org/uniprot/THB_CAIMO", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D006321", "http://www.uniprot.org/uniprot/THA_CAIMO", "http://www.uniprot.org/uniprot/TR150_HUMAN", "http://www.uniprot.org/uniprot/THA_PIG", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011988", "http://www.uniprot.org/uniprot/THBA_XENLA", "http://www.uniprot.org/uniprot/THB_PAROL", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D037021", "http://www.uniprot.org/uniprot/THA_HIPHI", "http://www.uniprot.org/uniprot/THB_DANRE", "http://www.uniprot.org/uniprot/THB_RAT", "http://www.uniprot.org/uniprot/THAA_DANRE", "http://www.uniprot.org/uniprot/THA_ELECQ", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0010861", "http://www.uniprot.org/uniprot/TR150_RAT", "http://www.uniprot.org/uniprot/TR150_MOUSE", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0004887", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0030375", "http://www.uniprot.org/uniprot/THA_SPAAU", "http://www.uniprot.org/uniprot/THA_NECMA", "http://www.uniprot.org/uniprot/THB_HUMAN", "http://www.uniprot.org/uniprot/THA_HUMAN", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D037042", "http://www.uniprot.org/uniprot/THA_SHEEP", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D015444", "http://www.uniprot.org/uniprot/THAA_XENLA", "http://www.uniprot.org/uniprot/THB_CHICK", "http://www.uniprot.org/uniprot/THBB_XENLA", "http://www.uniprot.org/uniprot/THA_RAT", "http://www.uniprot.org/uniprot/THA_ONCMY", "http://www.uniprot.org/uniprot/THA_SALSA", "http://www.uniprot.org/uniprot/THB_MOUSE" ]

[ "Yes. The Drosophila Translational Control Element (TCE), a 12 nucleotide long sequence element, was demonstrated to be necessary for translational control of expression in the male germ line of Drosophila melanogaster." ]

[ "yes" ]

[ "Gene regulation in Drosophila spermatogenesis: analysis of protein binding at the translational control element TCE.", "We have previously identified a 12 nucleotide long sequence element, the TCE, that was demonstrated to be necessary for translational control of expression in the male germ line of Drosophila melanogaster (Schäfer et al., 1990).", "Gene regulation in Drosophila spermatogenesis: analysis of protein binding at the translational control element TCE", "The Drosophila Translational Control Element (TCE) is required for high-level transcription of many genes that are specifically expressed in testes", "Bioinformatic analyses of core promoter sequences from 190 genes that are specifically expressed in testes identified a 10 bp A/T-rich motif that is identical to the translational control element (TCE)", "The Drosophila Translational Control Element (TCE) is required for high-level transcription of many genes that are specifically expressed in testes." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/22984601", "http://www.ncbi.nlm.nih.gov/pubmed/8111973" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004330", "http://amigo.geneontology.org/amigo/term/GO:0007283", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013091", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D029721" ]

[ "Patients receiving abacavir develop an idiosyncratic hypersensitivity reaction that can include a wide range of symptoms. The most common are: fever, enathema, skin rash, nausea, vomiting, diarrhoea, cough, gastrointestinal disorders, anaphylactic shock, respiratory symptoms." ]

[ "fever", "enathema", "skin rash", "nausea", "vomiting", "diarrhea", "cough", "gastrointestinal disorders", "anaphylactic shock", "respiratory symptoms" ]

[ "patients receiving abacavir develop a hypersensitivity reaction, characterized by rash, fever and, occasionally, multisystemic involvement", "The predictors included any one of several specific symptoms commonly found with this reaction, a claims diagnosis of adverse effect of drug, anaphylactic shock or unspecified allergy, and a discontinuation in abacavir prior to completing a 90-day course of therapy.", "patients who receive abacavir develop an idiosyncratic hypersensitivity reaction. The most common symptoms are fever, skin rash and gastrointestinal disorders. Respiratory symptoms occurred in approximately 20% of patients who have hypersensitivity reaction. We describe the first case, to our knowledge, of hypesensitivity reaction characterized by enanthema and fever without skin rash promptly resolved after discontinuation of abacavir", "Abacavir is associated with an infrequent but potentially serious hypersensitivity reaction (HSR) that can include a wide range of signs and symptoms.", "Rash was associated with hypersensitivity (odds ratio [OR] = 13.1, P = 0.02) as was the presence of nausea (OR = 30, P < 0.001), vomiting (OR = 17.1, P = 0.001) or diarrhoea (OR = 22, P < 0.001). The number of gastrointestinal symptoms was also predictive of hypersensitivity reaction (", "the number of gastrointestinal symptoms (OR = 8.6, P = 0.0032), cough (OR = 0.039, P = 0.02) and rash (OR = 16.9, P = 0.07). Abacavir hypersensitivity is strongly associated with gastrointestinal (GI) symptoms." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/12719670", "http://www.ncbi.nlm.nih.gov/pubmed/12869229", "http://www.ncbi.nlm.nih.gov/pubmed/18855539", "http://www.ncbi.nlm.nih.gov/pubmed/17245797" ]

[ { "p": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseasome/class", "s": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseases/1297", "o": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseaseClass/Immunological" }, { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#type", "s": "http://linkedlifedata.com/resource/umls/label/A12061804", "o": "http://www.w3.org/2008/05/skos-xl#Label" }, { "p": "http://www.w3.org/2008/05/skos-xl#prefLabel", "s": "http://linkedlifedata.com/resource/umls/id/C1840547", "o": "http://linkedlifedata.com/resource/umls/label/A12061804" }, { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#type", "s": "http://linkedlifedata.com/resource/umls/label/A11948761", "o": "http://www.w3.org/2008/05/skos-xl#Label" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A11994170", "o": "ABACAVIR HYPERSENSITIVITY, SUSCEPTIBILITY TO" }, { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#type", "s": "http://linkedlifedata.com/resource/umls/label/A17030126", "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/A7589770", "o": "http://www.w3.org/2008/05/skos-xl#Label" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C1457887", "o": "http://linkedlifedata.com/resource/umls/label/A7589770" } ]

[ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004342", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D006967", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0002524", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012816", "http://www.biosemantics.org/jochem#4274474", "http://www.biosemantics.org/jochem#4239946", "http://www.biosemantics.org/jochem#4274473" ]

[ "I(f)-channel inhibition potentially exhibits beneficial effects in diastolic heart failure. In patients with heart failure with preserved ejection fraction (HFpEF), short-term treatment with ivabradine increased exercise capacity, with a contribution from improved left ventricular filling pressure response to exercise as reflected by the ratio of peak early diastolic mitral flow velocity to peak early diastolic mitral annular velocity. Ivabradine has demonstrated benefits in HFpEF without improving mortality.\tIn db/db, a model of HFpEF, ivabradine improved vascular stiffness, left ventricular contractility, and diastolic function. Furthermore, ivabradine reduces cardiac fibrosis in hypercholesterolemic rabbits." ]

[]

[ "Traditional agents with strong evidence in HFrEF have proved unsuccessful in HFpEF. Newer agents such as angiotensin receptor neprilysin inhibitor, sildenafil, and ivabradine have demonstrated benefits without improving mortality.", "In db/db, a model of HFPEF, selective HR reduction by If-inhibition improved vascular stiffness, LV contractility, and diastolic function. Therefore, If-inhibition might be a therapeutic concept for HFPEF, if confirmed in humans.", "Selective HR reduction with IVA reduces DD and cardiac fibrosis in hypercholesterolemic rabbits. These beneficial effects of IVA support testing pure HR reduction in patients with diastolic heart failure.", "Beside its use in therapy of coronary artery disease, I(f)-channel inhibition potentially exhibits beneficial effects in systolic and diastolic heart failure as well.", "In patients with HFpEF, short-term treatment with ivabradine increased exercise capacity, with a contribution from improved left ventricular filling pressure response to exercise as reflected by the ratio of peak early diastolic mitral flow velocity to peak early diastolic mitral annular velocity." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/22833515", "http://www.ncbi.nlm.nih.gov/pubmed/20005474", "http://www.ncbi.nlm.nih.gov/pubmed/23916925", "http://www.ncbi.nlm.nih.gov/pubmed/23274284", "http://www.ncbi.nlm.nih.gov/pubmed/21212673" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D054144", "http://www.biosemantics.org/jochem#4266225" ]

[ "Low fT3 is an independent predictor of death in chronic kidney disease, in particular in dialised patients at end-stage renal diseases." ]

[ "yes" ]

[ "Low T3 was particularly common (44.3 %), and clearly associated with increased 6- and 12-month mortality and decreased overall survival (log rank test, P=0.007). ", "Increased rT3 may be more common in ESRD patients than previously described, and together with decreased T3 it may serve as an indicator of poor prognosis in subsequent months.", "The presence of TFT alterations seems to not be associated with clinical and prognostic implications in AKI patients.", "Multivariate analysis, according to receiver operating characteristic (ROC) curves, showed that mortality was best predicted by total triiodothyronine (T3).", "Finally, low T3 but not low free triiodothyronine was associated with worse all-cause (Likelihood ratio = 45.4; P < 0.0001) and cardiovascular mortality (Likelihood ratio = 47.8; P < 0.0001) after adjustment for confounding factors.", " In Cox analyses, fT3 was a significant predictor of mortality independent of the main traditional as well as non-traditional risk factors.", "All-cause and CV mortality rates were significantly higher in patients with 'lower' T3 levels than in the 'higher' T3 group (113.4 vs 18.2 events per 1000 patient-years, P<0.001, and 49.8 vs 9.1 events per 1000 patient-years, P=0.001, respectively). The Kaplan-Meier analysis also showed significantly worse cumulative survival rates in the 'lower' T3 group (P<0.001). In the Cox regression analysis, low T3 was an independent predictor of all-cause mortality even after adjusting for traditional risk factors (hazard ratio=3.76, P=0.021). ", "In CKD patients with proteinuria, low T3 concentration predicted all-cause mortality and cardiovascular event independently of the severity of proteinuria.", "Low-T3 syndrome is a frequent finding among HD patients, but it does not predict outcome. However, serum fT3 level is a strong and inverse mortality predictor, in part explained by its underlying association with nutritional state and inflammation.", "These data suggest that low FT3 levels are not predictive for mortality in a subgroup of stable HD patients who could survive more than 12 months.", "Low fT3 is an independent predictor of death in hemodialysis patients. These data lend support to the hypothesis that thyroid dysfunction is implicated in the high risk of the ESRD population." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/958900", "http://www.ncbi.nlm.nih.gov/pubmed/21189433", "http://www.ncbi.nlm.nih.gov/pubmed/22419237", "http://www.ncbi.nlm.nih.gov/pubmed/17908160", "http://www.ncbi.nlm.nih.gov/pubmed/999108", "http://www.ncbi.nlm.nih.gov/pubmed/19367004", "http://www.ncbi.nlm.nih.gov/pubmed/16230785", "http://www.ncbi.nlm.nih.gov/pubmed/21389695", "http://www.ncbi.nlm.nih.gov/pubmed/20178724", "http://www.ncbi.nlm.nih.gov/pubmed/18211669", "http://www.ncbi.nlm.nih.gov/pubmed/22881233", "http://www.ncbi.nlm.nih.gov/pubmed/17082213", "http://www.ncbi.nlm.nih.gov/pubmed/23857979", "http://www.ncbi.nlm.nih.gov/pubmed/16775599", "http://www.ncbi.nlm.nih.gov/pubmed/22260378", "http://www.ncbi.nlm.nih.gov/pubmed/7385804" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011379", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005067", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D058186", "http://www.disease-ontology.org/api/metadata/DOID:784", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D051437", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D051436" ]

[ "BMS is observed principally in middle-aged patients and postmenopausal women \nBMS mostly affects elderly citizens, especially postmenopausal women with prevalence up to 12-18%." ]

[ "yes" ]

[ "It is observed principally in middle-aged patients and postmenopausal women and may be accompanied by xerostomia and altered taste.", "It occurs more commonly in middle-aged and elderly women and often affects the tongue tip and lateral borders, lips, and hard and soft palate. ", "BMS is a chronic disorder that frequently affects women and is characterised by burning symptoms of the oral mucosa without clinical signs.", "It mostly affects elderly citizens, especially postmenopausal women with prevalence up to 12-18%. " ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/8725589", "http://www.ncbi.nlm.nih.gov/pubmed/17439072", "http://www.ncbi.nlm.nih.gov/pubmed/15055637", "http://www.ncbi.nlm.nih.gov/pubmed/18985004", "http://www.ncbi.nlm.nih.gov/pubmed/10431669", "http://www.ncbi.nlm.nih.gov/pubmed/12017897", "http://www.ncbi.nlm.nih.gov/pubmed/23772971", "http://www.ncbi.nlm.nih.gov/pubmed/23201368", "http://www.ncbi.nlm.nih.gov/pubmed/15911160", "http://www.ncbi.nlm.nih.gov/pubmed/3476895", "http://www.ncbi.nlm.nih.gov/pubmed/21685517", "http://www.ncbi.nlm.nih.gov/pubmed/21528120", "http://www.ncbi.nlm.nih.gov/pubmed/17967714", "http://www.ncbi.nlm.nih.gov/pubmed/20701667", "http://www.ncbi.nlm.nih.gov/pubmed/20230455", "http://www.ncbi.nlm.nih.gov/pubmed/12907696", "http://www.ncbi.nlm.nih.gov/pubmed/12764983", "http://www.ncbi.nlm.nih.gov/pubmed/19689438", "http://www.ncbi.nlm.nih.gov/pubmed/16142094", "http://www.ncbi.nlm.nih.gov/pubmed/17849966", "http://www.ncbi.nlm.nih.gov/pubmed/20440632", "http://www.ncbi.nlm.nih.gov/pubmed/8170453", "http://www.ncbi.nlm.nih.gov/pubmed/7838464", "http://www.ncbi.nlm.nih.gov/pubmed/11871678", "http://www.ncbi.nlm.nih.gov/pubmed/12618668", "http://www.ncbi.nlm.nih.gov/pubmed/19450321", "http://www.ncbi.nlm.nih.gov/pubmed/19658340", "http://www.ncbi.nlm.nih.gov/pubmed/22612823", "http://www.ncbi.nlm.nih.gov/pubmed/23050296", "http://www.ncbi.nlm.nih.gov/pubmed/24096230", "http://www.ncbi.nlm.nih.gov/pubmed/17452954", "http://www.ncbi.nlm.nih.gov/pubmed/17541900", "http://www.ncbi.nlm.nih.gov/pubmed/9237148", "http://www.ncbi.nlm.nih.gov/pubmed/11441716", "http://www.ncbi.nlm.nih.gov/pubmed/21903545", "http://www.ncbi.nlm.nih.gov/pubmed/20597947", "http://www.ncbi.nlm.nih.gov/pubmed/9844361", "http://www.ncbi.nlm.nih.gov/pubmed/18305436", "http://www.ncbi.nlm.nih.gov/pubmed/21418666", "http://www.ncbi.nlm.nih.gov/pubmed/10478959", "http://www.ncbi.nlm.nih.gov/pubmed/7629360", "http://www.ncbi.nlm.nih.gov/pubmed/11603307", "http://www.ncbi.nlm.nih.gov/pubmed/15024358", "http://www.ncbi.nlm.nih.gov/pubmed/22030140", "http://www.ncbi.nlm.nih.gov/pubmed/16905808", "http://www.ncbi.nlm.nih.gov/pubmed/18558051", "http://www.ncbi.nlm.nih.gov/pubmed/15195716", "http://www.ncbi.nlm.nih.gov/pubmed/18625105", "http://www.ncbi.nlm.nih.gov/pubmed/23787507", "http://www.ncbi.nlm.nih.gov/pubmed/10446526", "http://www.ncbi.nlm.nih.gov/pubmed/16637799", "http://www.ncbi.nlm.nih.gov/pubmed/8469539", "http://www.ncbi.nlm.nih.gov/pubmed/2700889", "http://www.ncbi.nlm.nih.gov/pubmed/20038880", "http://www.ncbi.nlm.nih.gov/pubmed/6589575", "http://www.ncbi.nlm.nih.gov/pubmed/18278306" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D002054", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D002056", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D008593", "http://www.disease-ontology.org/api/metadata/DOID:403", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016387", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D014930", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009055", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D017698", "http://www.disease-ontology.org/api/metadata/DOID:4331" ]

[ "CD99 is a hallmark marker for Ewing sarcoma and primitive neuroectodermal tumors." ]

[ "CD99" ]

[ "half of B-LBL patients are negative for CD45 (leucocyte common antigen, LCA), a widely used marker for the diagnosis of lymphoma, and a significant portion express CD99, a marker for Ewing's sarcoma (ES) or primitive neuroectodermal tumor (PNET)", "Moreover, half of B-LBL patients are negative for CD45 (leucocyte common antigen, LCA), a widely used marker for the diagnosis of lymphoma, and a significant portion express CD99, a marker for Ewing's sarcoma (ES) or primitive neuroectodermal tumor (PNET)" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/12783138" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D015415", "http://www.disease-ontology.org/api/metadata/DOID:4980", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012512", "http://www.disease-ontology.org/api/metadata/DOID:3368" ]

[ "Selected proteins of interest proposed from triple-negative cancer proteomic studies are CD44, PARP1, Mage-A4, LSR, RAB25, S100A14, MUC1, Hsp90, Actin, 14-3-3, vimentin, HSP70, CK18, moesin, IDH2, CRABP2, SEC14L2, beta-catenin, MUC18, Stat1 and CD74." ]

[ "CD44", "PARP1", "Mage-A4", "LSR", "RAB25", "S100A14", "MUC1", "Hsp90", "Actin", "14-3-3", "vimentin", "HSP70", "CK18", "moesin", "IDH2", "CRABP2", "SEC14L2", "beta-catenin", "MUC18", "Stat1", "CD74" ]

[ "Some of these proteins are of outstanding interest in the biology and clinical management of this disease, such as CD44 and PARP1.", "We present here our results, including a large cumulative database of proteins based on the analysis of 78 TNBCs, and the identification and validation of one specific protein, Mage-A4, which was expressed in a significant fraction of TNBC and Her2-positive/ER negative lesions.", "Proteomic profiling of triple-negative breast carcinomas in combination with a three-tier orthogonal technology approach identifies Mage-A4 as potential therapeutic target in estrogen receptor negative breast cancer.", "Further, we performed comparative quantitative proteomic and gene array analyses of these cells and identified potential novel markers of breast cancer cells with tumor-initiating features, such as lipolysis-stimulated lipoprotein receptor (LSR), RAB25, S100A14 and mucin 1 (MUC1), as well as a novel 31-gene signature capable of predicting distant metastasis in cohorts of estrogen receptor-negative human breast cancers.", "he results identify Hsp90 as a critical and multimodal target in this most difficult to treat breast cancer subtype and support the use of the Hsp90 inhibitor PU-H71 for clinical trials involving patients with TNBC.", "We obtained differential expression patterns for several glycolytic enzymes (as for example MDH2, PGK1, TKT, Aldolase1), cytokeratins (CK7, 8, 9, 14, 17, 19), further structure proteins (vimentin, fibronectin, L-plastin), for NME1-NME2, lactoferrin, and members of the Annexin family.", "he expression of calreticulin, cellular retinoic acid-binding protein II, chloride intracellular channel protein 1, EF-1-beta, galectin 1, peroxiredoxin-2, platelet-derived endothelial cell growth factor, protein disulfide isomerase and ubiquitin carboxyl-terminal hydrolase 5 were further validated using a tissue microarray containing 70 malignant breast carcinomas of various grades of atypia.", "The first is characterized by high expression of Stat1, Mx1, and CD74.", "This effect was accompanied with a marked increase in the membrane expression of beta-catenin, MUC18, plexins, integrins, and other proteins involved in cell adhesion and cancer metastasis. Taken together, our results show that Stat1/CD74 positive triple-negative tumors are more aggressive and suggest an approach for development of better diagnostics and more targeted therapies for triple negative breast cancer.", "Proteomic analysis also identified high levels of IDH2 and CRABP2 and low levels of SEC14L2 to be prognostic markers for overall breast cancer survival.", "Proteomic and validation immunohistochemical analyses revealed that alpha-defensins (DEFA) were overexpressed in tumors from patients with a pCR.", "The expression of a selected group of high abundance and/or breast cancer-specific potential biomarkers including thromobospondin 1, galectin-3 binding protein, cathepsin D, vimentin, zinc-α2-glycoprotein, CD44, and EGFR from the breast cancer cell lines and in their culture media were further validated by Western blot analysis.", "his provided novel evidence for PMA regulation of the enzymes glyceraldehyde-3-phosphate dehydrogenase, nucleolar RNA helicase 2 and Heterogeneous nuclear ribonucleoprotein M.", "Among them, we identify downregulation of components of the Ras/Raf/MAPK pathway and G(2)-M phase to contribute to its anti-proliferative effect, degradation of activated Akt and Bcl-xL to induce apoptosis, and inhibition of activated NF-kappaB, Akt, ERK2, Tyk2, and PKC to reduce TNBC invasive potential." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/19416831", "http://www.ncbi.nlm.nih.gov/pubmed/23172894", "http://www.ncbi.nlm.nih.gov/pubmed/22414580", "http://www.ncbi.nlm.nih.gov/pubmed/20068102", "http://www.ncbi.nlm.nih.gov/pubmed/22692575", "http://www.ncbi.nlm.nih.gov/pubmed/19485423", "http://www.ncbi.nlm.nih.gov/pubmed/23436753", "http://www.ncbi.nlm.nih.gov/pubmed/22178447", "http://www.ncbi.nlm.nih.gov/pubmed/22934887", "http://www.ncbi.nlm.nih.gov/pubmed/21630460", "http://www.ncbi.nlm.nih.gov/pubmed/20005186" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D020543", "http://www.disease-ontology.org/api/metadata/DOID:0060081", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D040901" ]

[ "Tuberous Sclerosis is a multisystem genetic disorder caused by mutation in TSC1 or TSC2 gene, that leads to hyperactivation of the mTOR signalling pathway, and subsequent dysregulation of cell growth control." ]

[ "Tuberous Sclerosis is caused by hyperactivation of the mTOR signalling pathway." ]

[ "Tuberous Sclerosis Complex (TSC) is a multisystem genetic disorder caused by mutation in either Tsc1 or Tsc2 genes that leads to the hyper activation of the mTOR pathway, a key signalling pathway for synaptic plasticity. ", "Tuberous sclerosis, caused by germline mutations in the TSC1 or TSC2 genes, is associated with aberrant upregulation of the mammalian target of rapamycin (mTOR) signalling pathway, resulting in growth of tumours, including renal angiomyolipomas (AMLs).", "Tuberous Sclerosis Complex is genetically determined with an autosomal dominant inheritance and is caused by inactivating mutations in either the TSC1 or TSC2 genes. TSC1/2 genes play a fundamental role in the regulation of phosphoinositide 3-kinase (PI3K) signalling pathway, inhibiting the mammalian target of rapamycin (mTOR) through activation of the GTPase activity of Rheb.", "TSC is an autosomal dominant disorder caused by mutation in either of two genes: TSC1, encoding hamartin, and TSC2, encoding tuberin. Both proteins form a complex inhibiting mTOR signalling pathway and thus regulate cell size and proliferation.", "Recent findings from this laboratory and others suggests that the tumour suppressor complex made of two proteins TSC1/hamartin and TSC2/tuberin, acts as a negative regulator of mTOR/S6K1 signalling. Mutations in either TSC1 or TSC2 are genetically linked to tuberous sclerosis complex (TSC) syndrome, which can lead to severe pathological consequences, including mental retardation, epilepsy and autism, as well as cardiac, pulmonary and renal failure.", "Here we review recent findings demonstrating that the TSC1/TSC2 inhibitory complex normally acts on Rheb to mediate mTOR/S6K1-signalling.", "Ras homologue enriched in brain (Rheb) represents a unique group of small GTPases and shares moderate sequence identity with the Ras/Rap subfamily. It acts downstream of nutrient signalling as the direct target of the tuberous sclerosis complex (TSC) and upstream of mTOR/S6K1/4EBP in the insulin-signalling pathway.", "Recent studies suggest that the tuberous sclerosis complex Tsc1-Tsc2 may couple insulin signalling to Tor activity", "Our genetic and biochemical analyses suggest that Rheb functions downstream of the tumour suppressors Tsc1 (tuberous sclerosis 1)-Tsc2 in the TOR (target of rapamycin) signalling pathway to control growth", "Our results indicate activation of a mammalian target of rapamycin metabolic pathway in tuberous sclerosis lesions, which contributes to their growth.", "Tuberous sclerosis (TSC) is an autosomal dominant hamartoma syndrome whose causative genes (TSC1 and TSC2) were identified 5 and 9 years ago respectively.", "Recent studies in Drosophila have pinpointed a critical function for the DrosophilaTSC1/TSC2 homologues in the regulation of cell size. Epistasis experiments and a variety of biochemical studies that followed have indicated a critical function for these proteins in the highly conserved PI-3-kinase-Akt-mTOR signalling pathway.", "Here, we show that tuberous sclerosis 1 (Tsc1) and Tsc2, tumour suppressors that are responsible for the tuberous sclerosis syndrome, antagonize this amino acid-TOR signalling pathway. We show that Tsc1 and Tsc2 can physically associate with TOR and function upstream of TOR genetically. In Drosophila melanogaster and mammalian cells, loss of Tsc1 and Tsc2 results in a TOR-dependent increase of S6K activity." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/20457704", "http://www.ncbi.nlm.nih.gov/pubmed/19506736", "http://www.ncbi.nlm.nih.gov/pubmed/15388940", "http://www.ncbi.nlm.nih.gov/pubmed/12766776", "http://www.ncbi.nlm.nih.gov/pubmed/12766775", "http://www.ncbi.nlm.nih.gov/pubmed/23159330", "http://www.ncbi.nlm.nih.gov/pubmed/12556239", "http://www.ncbi.nlm.nih.gov/pubmed/12172555", "http://www.ncbi.nlm.nih.gov/pubmed/12711473", "http://www.ncbi.nlm.nih.gov/pubmed/18368626", "http://www.ncbi.nlm.nih.gov/pubmed/15562827" ]

[]

[ "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.disease-ontology.org/api/metadata/DOID:13515", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D014402", "http://www.uniprot.org/uniprot/TSC2_MOUSE", "http://www.uniprot.org/uniprot/TSC1_HUMAN", "http://www.biosemantics.org/jochem#4266396", "http://www.uniprot.org/uniprot/TSC1_MOUSE", "http://www.uniprot.org/uniprot/TSC2_HUMAN" ]

[ "Our results suggested that life style changes which related to migration might reduce DNA damage in Hasake nationalities." ]

[ "yes" ]

[ "The CFS group had an unfavorable lipid profile and signs of oxidative stress induced damage to lipids and proteins. These results might be indicative of early proatherogenic processes in this group of patients who are otherwise at low risk for atherosclerosis. Antioxidant treatment and life style changes are indicated for women with CFS, as well as closer observation in order to assess the degree of atherosclerosis.", "Once detected, these patients may be offered more aggressive treatment strategies such as early pharmacotherapy in addition to life style changes targeted to maintaining pericyte integrity.", "Our results suggested that life style changes which related to migration might reduce DNA damage in Hasake nationalities.", "Low levels of antioxidants and increased oxidative stress with insulin resistance in metabolic syndrome suggests that besides therapeutic life style changes (TLC) as suggested in ATP III guidelines inclusion of antioxidant vitamins, fruits and vegetable could be beneficial to ward off the consequences of metabolic syndrome." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/21150342", "http://www.ncbi.nlm.nih.gov/pubmed/23185200", "http://www.ncbi.nlm.nih.gov/pubmed/19031760", "http://www.ncbi.nlm.nih.gov/pubmed/23105513" ]

[ { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A18450882", "o": "D008019" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A18450882", "o": "Life Style Induced Illness" }, { "p": "http://www.w3.org/2008/05/skos-xl#prefLabel", "s": "http://linkedlifedata.com/resource/umls/id/C2936742", "o": "http://linkedlifedata.com/resource/umls/label/A18450882" }, { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A18450882", "o": "MeSH" } ]

[ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D008019", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D018384" ]

[ "There is no clear evidence of the relationship between sweating and anaerobic threshold" ]

[ "There is no clear evidence of the relationship between sweating and anaerobic threshold" ]

[ "It is concluded that the sweating response during upright recovery is significantly modified by exercise intensity and may likely be influenced by the nonthermal baroreceptor reflex adjustments postexercise.", " The purpose of this paper is to delineate the effects of training status, heat acclimation, environmental conditions and host factors on the sweating response to exercise.", "These results would suggest that at a given exercise intensity in subjects with a higher aerobic capacity body temperature is maintained with a lower sweating rate than that in subjects with a lower aerobic capacity." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/2703281", "http://www.ncbi.nlm.nih.gov/pubmed/7588694", "http://www.ncbi.nlm.nih.gov/pubmed/9694410", "http://www.ncbi.nlm.nih.gov/pubmed/12937031" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D015308", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D008660", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013546" ]

[ "Elotuzumab is a humanized monoclonal antibody specific for signaling lymphocytic activation molecule-F7 (SLAMF7, also known as CS1, CD319, or CRACC) that enhances natural killer cell-mediated antibody-dependent cellular cytotoxicity of SLAMF7-expressing myeloma cells." ]

[ "signaling lymphocytic activation molecule-F7" ]

[ "BACKGROUND: Elotuzumab, an immunostimulatory monoclonal antibody targeting signaling lymphocytic activation molecule F7 (SLAMF7), showed activity in combination with lenalidomide and dexamethasone in a phase 1b-2 study in patients with relapsed or refractory multiple myeloma.", "Elotuzumab is a humanized monoclonal antibody specific for signaling lymphocytic activation molecule-F7 (SLAMF7, also known as CS1, CD319, or CRACC) that enhances natural killer (NK) cell-mediated antibody-dependent cellular cytotoxicity (ADCC) of SLAMF7-expressing myeloma cells.", "This led to development of an anti-SLAMF7 antibody, elotuzumab, showing efficacy against MM.", "One of the most promising MoAb is elotuzumab, the only humanized IgG1 MoAb specifically targeting CS1 (SLAMF7), a cell surface glycoprotein that is highly expressed in plasma cells. ", "This led to development of an anti-SLAMF7 antibody, elotuzumab, showing efficacy against MM.", "Elotuzumab is a humanized monoclonal antibody specific for signaling lymphocytic activation molecule-F7 (SLAMF7, also known as CS1, CD319, or CRACC) that enhances natural killer (NK) cell-mediated antibody-dependent cellular cytotoxicity (ADCC) of SLAMF7-expressing myeloma cells.", " New agents are awaited for the treatment of multiple myeloma and research is ongoing for the development of monoclonal antibodies (MoAbs) targeting the tumor cells. One of the most promising MoAb is elotuzumab, the only humanized IgG1 MoAb specifically targeting CS1 (SLAMF7), a cell surface glycoprotein that is highly expressed in plasma cells.", "This led to development of an anti-SLAMF7 antibody, elotuzumab, showing efficacy against MM.", "Elotuzumab, an immunostimulatory monoclonal antibody targeting signaling lymphocytic activation molecule F7 (SLAMF7), showed activity in combination with lenalidomide and dexamethasone in a phase 1b-2 study in patients with relapsed or refractory multiple myeloma." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/26035255", "http://www.ncbi.nlm.nih.gov/pubmed/25287778", "http://www.ncbi.nlm.nih.gov/pubmed/25312647", "http://www.ncbi.nlm.nih.gov/pubmed/24941981" ]

[]

[ "http://www.uniprot.org/uniprot/SLAF7_HUMAN", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D000911" ]

[ "Bedaquiline works by inhibiting bacterial adenosine triphosphate (ATP) synthase and represents the first novel class of antituberculosis agents that is used for treatment of multi drug resistant tuberculosis." ]

[]

[ "Bedaquiline works by inhibiting bacterial adenosine triphosphate (ATP) synthase and represents the first novel class of antituberculosis agents in more than 40 years. ", "Bedaquiline has an entirely novel mechanism of action and so should be active against otherwise highly resistant organisms. It acts on the transmembrane component of adenosine triphosphate synthase and acts by preventing electron transport.", "Bedaquiline - The first ATP synthase inhibitor against multi drug resistant tuberculosis.", " Bedaquiline is an anti-tuberculosis drug with unique mechanism of action. It selectively inhibits the mycobacterial energy metabolism i.e. ATP synthesis and found to be effective against all states of Mycobacterium tuberculosis like active, dormant, replicating, non-replicating, intracellular and extracellular.", "DATA SYNTHESIS: Bedaquiline possesses a unique mechanism of action that disrupts the activity of the mycobacterial adenosine triphosphate synthase. ", "By directly inhibiting adenosine triphosphate (ATP) synthase, bedaquiline is effective against both replicating and dormant mycobacteria. ", "Enhanced sterilizing capacity via synergistic depletion of ATP further exhibits the promising potential of bedaquiline with pyrazinamide. ", "Bedaquiline possesses a unique mechanism of action that disrupts the activity of the mycobacterial adenosine triphosphate synthase" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/24563587", "http://www.ncbi.nlm.nih.gov/pubmed/25203970", "http://www.ncbi.nlm.nih.gov/pubmed/25114537", "http://www.ncbi.nlm.nih.gov/pubmed/24173008", "http://www.ncbi.nlm.nih.gov/pubmed/23459487", "http://www.ncbi.nlm.nih.gov/pubmed/24259600" ]

[]

[]

[ "Findings regarding association between helicobacter pylori infection and ischemic stroke risk are conflicting. There is evidence to suggest that helicobacter pylori infection is associated with increased risk for ischemic stroke and should be considered stroke risk factors. However, some studies reported no association between helicobacter pylori infection and stroke." ]

[]

[ "Helicobacter pylori (H. pylori) infection is reported to be associated with many extragastrointestinal manifestations, such as hematological diseases [idiopathic thrombocytopenic purpura (ITP) and unexplained iron deficiency anemia (IDA)], cardiovascular diseases (ischemic heart diseases), neurological disorders (stroke, Parkinson's disease, Alzheimer's disease), obesity and skin disorders.", "Helicobacter pylori infection contributes to high risk of ischemic stroke: evidence from a meta-analysis.", "This meta-analysis indicated that chronic H. pylori infection was significantly associated with an increased risk of IS, especially for non-cardioembolic IS. ", "In the last years, a considerable number of studies have been performed on the relationship between infection from Helicobacter Pylori and atherosclerotic diseases, like stroke and ischemic heart disease. ", "However, there are conflicting results on the relevance of chronic infection by Helicobacter pylori as a risk factor for ischemic stroke.", "CONCLUSIONS: This case-control study does not reveal any strong association between chronic Helicobacter pylori infection and ischemic stroke. ", "Case-control and prospective studies indicate that chronic infections, such as periodontitis, chronic bronchitis and infection with Helicobacter pylori, Chlamydia pneumoniae or Cytomegalovirus, might increase stroke risk, although considerable variation exists in the results of these studies, and methodological issues regarding serological results remain unresolved.", "Chronic infections, presently discussed as stroke risk factors mainly include periodontitis and infections with Helicobacter pylori (Hp) and Chlamydia pneumoniae (Cp). ", "CONCLUSION: H. Pylori gastritis is not independently associated with increased risk for stroke. ", "CONCLUSIONS: Our results support the hypothesis that CagA-seropositive strains infection is significantly associated with susceptibility to ischemic strokes and coronary heart diseases. ", "BACKGROUND: Previous studies suggested an association between CagA-positive H. pylori strains and ischemic stroke. ", "CONCLUSIONS: Our findings suggest that CagA-positive strains of H. pylori are significantly associated to atherosclerotic stroke.", "We concluded that H pylori infection is common in DM and seems to be linked to the presence of atherosclerosis and ischemic cerebrovascular stroke. ", "Interesting results show that H. pylori infection affects atherosclerosis and is weakly associated with ischemic heart disease and stroke. Moreover, CagA-positive H. pylori strains may play a role in the natural history of atherosclerotic stroke.", "Interestingly, the majority of the extradigestive-related literature is focused on two vascular manifestations: stroke and ischemic heart disease. ", "Chronic infectious diseases that may increase the risk of stroke include periodontitis, chronic bronchitis and infections with microbial antigens, such as Helicobacter pylori and Chlamydia pneumoniae. ", "CONCLUSIONS: These results suggest that H. pylori infection is a risk factor for ischemic stroke and that CD14 polymorphism is not.", " CONCLUSIONS: Our case-control study provides evidence of an association between the immune response to H. pylori , a marker of prior infection with this organism and noncardioembolic ischemic stroke.", "Case-control studies and a few prospective studies have indicated that chronic infections may add to the risk of stroke and that acute infections may act as trigger factors for stroke. Such chronic infections include periodontal disease, infection with Chlamydia pneumoniae or Helicobacter pylori, and chronic bronchitis", "Chronic H. pylori infection still showed an overall association with ischemic stroke (odds ratio for all subtypes combined: 2.57; 95% CI: 1.09-6.08) after adjusting for major cardiovascular risk factors. These results suggest that chronic H. pylori infection may be a triggering factor that increases the risk of acute ischemic stroke.", "BACKGROUND AND PURPOSE: Studies on Helicobacter pylori infection and risk of ischemic stroke yielded variable results. ", "CONCLUSIONS: Our results support the hypothesis of an association between infection with CagA-positive H. pylori strains and acute cerebral ischemia.", " Chronic infections (eg, infection with Chlamydia pneumoniae or Helicobacter pylori) were found to increase the risk of stroke; however, study results are at variance, residual confounding is not excluded, and causality is not established at present. ", "CONCLUSIONS: Infection with Helicobacter pylori is associated with an increased risk of stroke and increased fibrinogen levels but these findings can be attributed to a confounding effect of socio-economic status.", " CONCLUSIONS: Hp infection represents risk factor of ischemic stoke via an interaction of Hp cytotoxins or cytokines with atherosclerotic plaques in carotic arteries.", "CONCLUSIONS: The association between H pylori and acute cerebrovascular disease seems to be due to a higher prevalence of more virulent H pylori strains in patients with atherosclerotic stroke.", "CONCLUSIONS: H. pylori infection appears to be significantly more frequent in middle-aged patients with acute ischemic stroke than in controls.", "Chronic H pylori infection was associated with a higher risk of stroke caused by small-artery occlusion (adjusted odds ratio, 3.31; 95% CI, 1.15 to 9.56) and a lower risk of cardioembolic stroke (adjusted odds ratio, 0.21; 95% CI, 0.06 to 0.71). Overall, elevated H pylori as well as elevated C pneumoniae antibodies were not associated with ischemic stroke.", "Presently, it is insufficiently established whether Helicobacter pylori infection represents a risk factor for ischemic stroke.", " H. pylori seropositivity may be an independent risk factor for stroke of atherothrombotic origin.", "Appropriately randomized studies employing an antibiotic treatment for patients affected by ischemic vascular disease will answer the question of whether H. pylori has a causal role in the pathogenesis of acute myocardial infarction and ischemic stroke.", "Results on the association between this bacterium and acute myocardial infarction or stroke are controversial, due to the degree of studies heterogeneity. ", "Interventional randomized studies employing an antibiotic treatment for patients affected by ischemic vascular diseases will rapidly answer the question of wheather Helicobacter pylori has a causal role in the pathogenesis of acute myocardial infarction and ischemic stroke.", " CONCLUSION: Chronic H pylori infection is an independent risk factor for ischaemic cerebrovascular disease and may act, at least in part, by increasing atherosclerosis.", "Presently, it is insufficiently established whether Helicobacter pylori infection represents a risk factor for ischemic stroke.", "This case-control study does not reveal any strong association between chronic Helicobacter pylori infection and ischemic stroke.", "However, there are conflicting results on the relevance of chronic infection by Helicobacter pylori as a risk factor for ischemic stroke.", "Chronic infections (eg, infection with Chlamydia pneumoniae or Helicobacter pylori) were found to increase the risk of stroke; however, study results are at variance, residual confounding is not excluded, and causality is not established at present.", "BACKGROUND AND PURPOSE: Studies on Helicobacter pylori infection and risk of ischemic stroke yielded variable results.", "This case-control study does not reveal any strong association between chronic Helicobacter pylori infection and ischemic stroke.", "Presently, it is insufficiently established whether Helicobacter pylori infection represents a risk factor for ischemic stroke", "Chronic infectious diseases that may increase the risk of stroke include periodontitis, chronic bronchitis and infections with microbial antigens, such as Helicobacter pylori and Chlamydia pneumoniae", "Studies on Helicobacter pylori infection and risk of ischemic stroke yielded variable results", "Presently, it is insufficiently established whether Helicobacter pylori infection represents a risk factor for ischemic stroke", "However, there are conflicting results on the relevance of chronic infection by Helicobacter pylori as a risk factor for ischemic stroke" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/12063957", "http://www.ncbi.nlm.nih.gov/pubmed/18988408", "http://www.ncbi.nlm.nih.gov/pubmed/21060340", "http://www.ncbi.nlm.nih.gov/pubmed/15694938", "http://www.ncbi.nlm.nih.gov/pubmed/18249521", "http://www.ncbi.nlm.nih.gov/pubmed/22713083", "http://www.ncbi.nlm.nih.gov/pubmed/12725602", "http://www.ncbi.nlm.nih.gov/pubmed/19355997", "http://www.ncbi.nlm.nih.gov/pubmed/18665936", "http://www.ncbi.nlm.nih.gov/pubmed/12388919", "http://www.ncbi.nlm.nih.gov/pubmed/11588309", "http://www.ncbi.nlm.nih.gov/pubmed/22688569", "http://www.ncbi.nlm.nih.gov/pubmed/11157171", "http://www.ncbi.nlm.nih.gov/pubmed/17669100", "http://www.ncbi.nlm.nih.gov/pubmed/11155465", "http://www.ncbi.nlm.nih.gov/pubmed/16230797", "http://www.ncbi.nlm.nih.gov/pubmed/21775946", "http://www.ncbi.nlm.nih.gov/pubmed/11253332", "http://www.ncbi.nlm.nih.gov/pubmed/18346651", "http://www.ncbi.nlm.nih.gov/pubmed/14500942", "http://www.ncbi.nlm.nih.gov/pubmed/16386288", "http://www.ncbi.nlm.nih.gov/pubmed/16004850", "http://www.ncbi.nlm.nih.gov/pubmed/9805426", "http://www.ncbi.nlm.nih.gov/pubmed/24890556", "http://www.ncbi.nlm.nih.gov/pubmed/21669114", "http://www.ncbi.nlm.nih.gov/pubmed/18706211", "http://www.ncbi.nlm.nih.gov/pubmed/16466297", "http://www.ncbi.nlm.nih.gov/pubmed/15166387", "http://www.ncbi.nlm.nih.gov/pubmed/12147540", "http://www.ncbi.nlm.nih.gov/pubmed/9436737", "http://www.ncbi.nlm.nih.gov/pubmed/11412864" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016480", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016481" ]

[ "Dysarthria is a motor speech disorder which can be classified according to the underlying neuropathology and is associated with disturbances of respiration, laryngeal function, airflow direction, and articulation resulting in difficulties of speech quality and intelligibility. There are six major types of dysarthria: \"flaccid dysarthria\" associated with lower motor neuron impairment, \"spastic dysarthria\" associated with damaged upper motor neurons linked to the motor areas of the cerebral cortex, \"ataxic dysarthria\" primarily caused by cerebellar dysfunction, and \"hyperkinetic dysarthria\" and \"hypokinetic dysarthria\", which are related to a disorder of the extrapyramidal system. The sixth is generally termed a \"mixed dysarthria\" and is associated with damage in more than one area, resulting in speech characteristics of at least two groups." ]

[ "flaccid dysarthria", "spastic dysarthria", "ataxic dysarthria", "hyperkinetic dysarthria", "hypokinetic dysarthria", "mixed dysarthria" ]

[ "Dysarthria is a motor speech disorder which can be classified according to the underlying neuropathology and is associated with disturbances of respiration, laryngeal function, airflow direction, and articulation resulting in difficulties of speech quality and intelligibility. There are six major types of dysarthria: flaccid dysarthria associated with lower motor neuron impairment, spastic dysarthria associated with damaged upper motor neurons linked to the motor areas of the cerebral cortex, ataxic dysarthria primarily caused by cerebellar dysfunction, and hyperkinetic dysarthria and hypokinetic dysarthria, which are related to a disorder of the extrapyramidal system. The sixth is generally termed a mixed dysarthria and is associated with damage in more than one area, resulting in speech characteristics of at least two groups.", "address voice problems of stroke patients with mixed dysarthria", "Characterizing intonation deficit in motor speech disorders: an autosegmental-metrical analysis of spontaneous speech in hypokinetic dysarthria, ataxic dysarthria", "ataxic dysarthria (AT)", "Acoustic analysis provides objective quantitative measures of speech that enable a comprehensive and accurate understanding of motor disorders and complement the traditional measures. This paper aims to distinguish between normal and pathological speech, more specifically between apraxia of speech and spastic dysarthria", "Long-term phonatory instability in ataxic dysarthria.", "The objective of this study is to evaluate phonation in ataxic dysarthria and a control group of normal speakers", "Dysprosody is a common feature in speakers with hypokinetic dysarthria.", "The prosodic profile of Cantonese speakers with hypokinetic dysarthria is similar to those of other languages (for example, English).", "Classification of dysarthria types comprises flaccid, spastic, ataxic, hypo- and hyperkinetic and mixed dysarthria.", "Dysarthria affects linguistic domains such as respiration, phonation, articulation, resonance and prosody due to upper motor neuron, lower motor neuron, cerebellar or extrapyramidal tract lesions.", "The dysarthria types were spastic (15 subjects), flaccid (10), mixed (12), hypokinetic (12), hyperkinetic (9) and ataxic (8).", "Dysarthria is a motor speech disorder which can be classified according to the underlying neuropathology and is associated with disturbances of respiration, laryngeal function, airflow direction, and articulation resulting in difficulties of speech quality and intelligibility.", "There are six major types of dysarthria: flaccid dysarthria associated with lower motor neuron impairment, spastic dysarthria associated with damaged upper motor neurons linked to the motor areas of the cerebral cortex, ataxic dysarthria primarily caused by cerebellar dysfunction, and hyperkinetic dysarthria and hypokinetic dysarthria, which are related to a disorder of the extrapyramidal system.", "There are six major types of dysarthria: flaccid dysarthria associated with lower motor neuron impairment, spastic dysarthria associated with damaged upper motor neurons linked to the motor areas of the cerebral cortex, ataxic dysarthria primarily caused by cerebellar dysfunction, and hyperkinetic dysarthria and hypokinetic dysarthria, which are related to a disorder of the extrapyramidal system.", "Motor neuron disease encompasses a group of terminal, demyelinating diseases affecting upper- and lower-motor neurons and producing muscular weakness resulting in a flaccid, spastic, or spastic-flaccid dysarthria of speech.", "Dysarthria is a frequently occurring motor speech disorder which can be caused by neurological trauma, cerebral palsy, or degenerative neurological diseases.", "Dysarthria is a motor disorder of speech characterized by abnormalities of the articulation and intelligibility of speech.", "There are six major types of dysarthria: flaccid dysarthria associated with lower motor neuron impairment, spastic dysarthria associated with damaged upper motor neurons linked to the motor areas of the cerebral cortex, ataxic dysarthria primarily caused by cerebellar dysfunction, and hyperkinetic dysarthria and hypokinetic dysarthria, which are related to a disorder of the extrapyramidal system" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/9197089", "http://www.ncbi.nlm.nih.gov/pubmed/22268902", "http://www.ncbi.nlm.nih.gov/pubmed/23422471", "http://www.ncbi.nlm.nih.gov/pubmed/10693258", "http://www.ncbi.nlm.nih.gov/pubmed/22774423", "http://www.ncbi.nlm.nih.gov/pubmed/19995207", "http://www.ncbi.nlm.nih.gov/pubmed/19295217", "http://www.ncbi.nlm.nih.gov/pubmed/18953144", "http://www.ncbi.nlm.nih.gov/pubmed/21088427", "http://www.ncbi.nlm.nih.gov/pubmed/23312647", "http://www.ncbi.nlm.nih.gov/pubmed/23033442", "http://www.ncbi.nlm.nih.gov/pubmed/20882349" ]

[]

[ "http://www.disease-ontology.org/api/metadata/DOID:92", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004401", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013064" ]

[ "Yes. In different cell types, induction of forkhead transcription factor FOXO1 was found to increase expression of the mitochondrial antioxidant manganese superoxide dismutase, and lead to suppression of oxidative stress." ]

[ "yes" ]

[ "Forkhead-box class O (FoxO) transcription factors regulate mechanisms of cellular aging, including protein quality control, autophagy and defenses against oxidative stress.", "Statin-mediated upregulation of klotho expression and differential regulation of FoxO expression promote resistance to CsA-induced oxidative stress.", "FoxO expression suppressed the ROS-induced apoptosis in differentiated 3T3-L1 cells via the expression of ROS-scavenging enzymes.", "Differential expression of FOXO1 and FOXO3a confers resistance to oxidative cell death upon endometrial decidualization.", "We demonstrate that human endometrial stromal cells become extraordinarily resistant to oxidative stress-induced apoptosis upon decidualization in response to cAMP and progesterone signaling. This differentiation process is associated with the induction of the forkhead transcription factor FOXO1, which in turn increases the expression of the mitochondrial antioxidant manganese superoxide dismutase.", "Comparative analysis demonstrated that hydrogen peroxide, a source of free radicals, strongly induces FOXO3a mRNA and protein expression in undifferentiated human endometrial stromal cells but not in decidualized cells.", "These results suggest that the induction of FOXO1 may enhance the ability of decidualized cells to prevent oxidative damage while the simultaneous repression of FOXO3a expression disables the signaling pathway responsible for oxidative cell death. The differential regulation of FOXO expression provides the decidua with a robust system capable of coping with prolonged episodes of oxidative stress during pregnancy." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/16709600", "http://www.ncbi.nlm.nih.gov/pubmed/19842039", "http://www.ncbi.nlm.nih.gov/pubmed/24269635", "http://www.ncbi.nlm.nih.gov/pubmed/22986347" ]

[]

[ "http://www.uniprot.org/uniprot/FOXO_DROME", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0006979", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0034599", "http://www.uniprot.org/uniprot/FOXO_CAEEL", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:1900407", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D018384" ]

[ "LINX Reflux Management System is a sphincter augmentation device designed to prevent gastroesophageal reflux due to abnormal opening of the lower esophageal sphincter (LES) by augmenting the sphincter barrier. It is implanted via laparoscopic procedure that does not alter gastric anatomy and is easily reversible." ]

[]

[ "Magnetic sphincter augmentation with the LINX device for gastroesophageal reflux disease after U.S. Food and Drug Administration approval.", "Magnetic sphincter augmentation (MSA) of the gastroesophageal junction with the LINX Reflux Management System is an alternative to fundoplication for gastroesophageal reflux disease (GERD) that was approved by the U.S. Food and Drug Administration (FDA) in March 2012. ", "Is the LINX reflux management system an effective treatment for gastro-oesophageal reflux disease?", "BACKGROUND: Laparoscopic magnetic sphincter augmentation (MSA) with the LINX device is a promising new therapy for the treatment of gastroesophageal reflux disease (GERD).", "Other nonmedical therapies include, the Stretta procedure, transoral incisionless fundoplication, and the magnetic sphincter augmentation device (LINX). ", "LINX(®) Reflux Management System in chronic gastroesophageal reflux: a novel effective technology for restoring the natural barrier to reflux.", " The LINX(®) Reflux Management System (Torax Medical, St. Paul, MN, USA) is designed to provide a permanent solution to GERD by augmenting the sphincter barrier with a standardized, reproducible laparoscopic procedure that does not alter gastric anatomy and is easily reversible.", "LINX(™) Reflux Management System: magnetic sphincter augmentation in the treatment of gastroesophageal reflux disease.", "The LINX(™) Reflux Management System (Torax Medical) is designed to provide a permanent solution to GERD by augmenting the physiologic function of the sphincter barrier with a simple and reproducible laparoscopic procedure that does not alter gastric anatomy and can be easily reversed if necessary.", "The Linx sphincter augmentation device has been developed to address this gap with improvement of the barrier function of LES and reversible design if necessary.", " METHODS: A sphincter augmentation device (LINX Reflux Management System; Torax Medical, Shoreview, MN), designed to prevent reflux due to abnormal opening of the lower esophageal sphincter (LES), was laparoscopically implanted at the gastroesophageal junction in 44 patients.", "Specific topics include reviews of long-term outcomes after laparoscopic antireflux surgery, the use of surgically placed implantable device for LES augmentation (Linx), the use of mesh for hiatal hernioplasty, and prone and nonthoracic approaches to minimally invasive esophagectomy.", "LINX( ) Reflux Management System: magnetic sphincter augmentation in the treatment of gastroesophageal reflux disease.", "METHODS: A sphincter augmentation device (LINX Reflux Management System; Torax Medical, Shoreview, MN), designed to prevent reflux due to abnormal opening of the lower esophageal sphincter (LES), was laparoscopically implanted at the gastroesophageal junction in 44 patients.", "BACKGROUND: Sphincter augmentation with the LINX� Reflux Management System is a surgical option for patients with chronic gastroesophageal disease (GERD) and an inadequate response to proton pump inhibitors (PPIs).", "A sphincter augmentation device (LINX Reflux Management System; Torax Medical, Shoreview, MN), designed to prevent reflux due to abnormal opening of the lower esophageal sphincter (LES), was laparoscopically implanted at the gastroesophageal junction in 44 patients", "Sphincter augmentation with the LINX Reflux Management System provided long-term clinical benefits with no safety issues, as demonstrated by reduced esophageal acid exposure, improved GERD-related quality of life, and cessation of dependence on PPIs, with minimal side effects and no safety issues", "The limitations of current therapy for GERD have encouraged a search for more effective treatment.The Linx sphincter augmentation device has been developed to address this gap with improvement of the barrier function of LES and reversible design if necessary." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/23155537", "http://www.ncbi.nlm.nih.gov/pubmed/23237251", "http://www.ncbi.nlm.nih.gov/pubmed/24117632", "http://www.ncbi.nlm.nih.gov/pubmed/21037442", "http://www.ncbi.nlm.nih.gov/pubmed/25062898", "http://www.ncbi.nlm.nih.gov/pubmed/24778041", "http://www.ncbi.nlm.nih.gov/pubmed/19951799", "http://www.ncbi.nlm.nih.gov/pubmed/25000345", "http://www.ncbi.nlm.nih.gov/pubmed/25012804", "http://www.ncbi.nlm.nih.gov/pubmed/23814607", "http://www.ncbi.nlm.nih.gov/pubmed/22538694", "http://www.ncbi.nlm.nih.gov/pubmed/25264655" ]

[]

[ "http://www.disease-ontology.org/api/metadata/DOID:8534" ]

[ "GM1 gangliosidoses are associated with deficiency of β-galactosidase." ]

[ "β-galactosidase" ]

[ "GM1 and GM2 gangliosidosis are associated with deficiency of β-galactosidase and β-hexosaminidase respectively", "The total content and distribution of retinal glycosphingolipids was studied for the first time in control mice and in Sandhoff disease (SD) and GM1 gangliosidosis mice", "The GSL abnormalities in the SD and the GM1 retinas reflect significant reductions in beta-hexosaminidase and beta-galactosidase enzyme activities, respectively", "In the absence of macular or retinal degeneration, organomegaly, and somatic-facial features suggesting mucopolysaccharidosis, the presence of hyperacusis together with sea-blue histiocytes in bone marrow biopsies and deficient beta-galactosidase activity but normal glucosidase, hexosaminidase, and neuraminidase activity on lysosomal enzyme assays constitutes the clinical-pathologic-biochemical profile of GM1 gangliosidosis type 2. This is a rare, late infantile onset, progressive gray-matter disease in which beta-galactosidase deficiency is largely localized to the brain, though it can be demonstrated in leukocytes and cultured skin fibroblasts", "GM1-gangliosidosis (genetic beta-galactosidase deficiency)", "GM1-gangliosidosis is a genetic neurological disorder caused by mutations in the lysosomal acid beta-galactosidase gene", "GM1-gangliosidosis is a rare neurovisceral storage disease caused by an inherited deficiency of acid beta-galactosidase", "A female infant with early-onset GM1-gangliosidosis type I was investigated. The lymphocytes, transformed lymphocytes and cultured skin fibroblasts of the patient were demonstrated to have severe beta-D-galactosidase deficiency", "Only 1 individual was found to have about 50% of normal beta-galactosidase activity; presumably he is a carrier for beta-galactosidase deficiency (GM1 gangliosidosis).", "GM1 gangliosidosis is a lysosomal storage disorder caused by mutations in the GLB1 gene, leading to the deficiency of the enzyme β-d-galactosidase", "GM1 gangliosidosis is a genetic disease with lysosomal beta-galactosidase deficiency caused by mutations of the gene coding for this enzyme", "GM1 gangliosidosis is a glycosphingolipid (GSL) lysosomal storage disease caused by a genetic deficiency of acid beta-galactosidase (beta-gal), the enzyme that catabolyzes GM1 within lysosomes", "Correction of acid beta-galactosidase deficiency in GM1 gangliosidosis human fibroblasts by retrovirus vector-mediated gene transfer: higher efficiency of release and cross-correction by the murine enzyme", "Review of the data is presented on the hereditary disease gangliosidosis GM1 and on the enzyme beta-galactosidose, deficiency of which is responsible for this disease", "GM1 gangliosidosis and Morquio B disease are distinct disorders both clinically and biochemically yet they arise from the same beta-galactosidase enzyme deficiency", "Heterogeneous patterns of biosynthesis, posttranslational processing, and degradation were demonstrated for mutant enzymes in three clinical forms of beta-galactosidase deficiency (beta-galactosidosis): juvenile GM1-gangliosidosis, adult GM1-gangliosidosis, and Morquio B disease.", "GM1 gangliosidosis and Morquio B disease are distinct disorders both clinically and biochemically yet they arise from the same beta-galactosidase enzyme deficiency.", "Cerebral lipids of patients with GM1-gangliosidoses, infantile, juvenile, and chronic type which are caused by deficiency of beta-galactosidase, were examined and compared to each other.", "In the autosomal recessive disease GM1-gangliosidosis caused by a beta-gal deficiency and in galactosialidosis, associated with a combined deficiency of lysosomal neuraminidase and beta-gal, precursor forms of the latter enzyme are found in RER, Golgi and some labeling is present at the cell surface. The lysosomes remain unlabeled, indicative for the absence of enzyme molecules in this organelle.", "In the lysosomes virtually all beta-gal exists as a high molecular weight multimer of mature enzyme. In the autosomal recessive disease GM1-gangliosidosis caused by a beta-gal deficiency and in galactosialidosis, associated with a combined deficiency of lysosomal neuraminidase and beta-gal, precursor forms of the latter enzyme are found in RER, Golgi and some labeling is present at the cell surface.", "In the autosomal recessive disease GM1-gangliosidosis caused by a beta-gal deficiency and in galactosialidosis, associated with a combined deficiency of lysosomal neuraminidase and beta-gal, precursor forms of the latter enzyme are found in RER, Golgi and some labeling is present at the cell surface.", "GM1 and GM2 gangliosidosis are associated with deficiency of β-galactosidase and β-hexosaminidase respectively." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/2837434", "http://www.ncbi.nlm.nih.gov/pubmed/8112731", "http://www.ncbi.nlm.nih.gov/pubmed/1909089", "http://www.ncbi.nlm.nih.gov/pubmed/3088302", "http://www.ncbi.nlm.nih.gov/pubmed/17442056", "http://www.ncbi.nlm.nih.gov/pubmed/25936995", "http://www.ncbi.nlm.nih.gov/pubmed/8068159", "http://www.ncbi.nlm.nih.gov/pubmed/2117086", "http://www.ncbi.nlm.nih.gov/pubmed/117628", "http://www.ncbi.nlm.nih.gov/pubmed/2123760", "http://www.ncbi.nlm.nih.gov/pubmed/1588015", "http://www.ncbi.nlm.nih.gov/pubmed/10757351", "http://www.ncbi.nlm.nih.gov/pubmed/10571006", "http://www.ncbi.nlm.nih.gov/pubmed/23622392", "http://www.ncbi.nlm.nih.gov/pubmed/3084261", "http://www.ncbi.nlm.nih.gov/pubmed/15086521" ]

[]

[]

[ "Cerebral hemiatrophy (atrophy of one cerebral hemisphere) is the characteristic feature of the Dyke-Davidoff-Masson syndrome. It develops due to an insult to the brain in fetal or early childhood period. Calvarial thickening, skull and facial asymmetry, contralateral hemiparesis, cognitive impairment and seizures are also characteristic to the Dyke-Davidoff-Masson syndrome.\n." ]

[ "cerebral hemiatrophy" ]

[ "Dyke-Davidoff-Masson syndrome is a rare condition characterized by cerebral hemiatrophy, calvarial thickening, skull and facial asymmetry, contralateral hemiparesis, cognitive impairment and seizures.", "Dyke-Davidoff-Masson syndrome refers to atrophy of one cerebral hemisphere (hemiatrophy) due to an insult to the brain in fetal or early childhood period. ", "Acquired cerebral hemiatrophy: Dyke-Davidoff-Masson Syndrome - a case report.", "CT and MRI scan of the head showed hemiatrophic cerebral parenchyma with prominent sulci and encephalomalacia.", "CT of the brain revealed characteristic features diagnostic of infantile type of cerebral hemiatrophy or Dyke-Davidoff-Masson syndrome.", "Magnetic resonance imaging (MRI) of brain revealed atrophic of left cerebral hemisphere with mildly ventricular dilatation, prominent paranasal and mastoid air cells, suggestive of Dyke-Davidoff-Masson syndrome (DDMS).", "Imaging showed resolution of the infection and features of Dyke-Davidoff-Masson syndrome (cerebral hemiatrophy). ", "Dyke-Davidoff-Masson syndrome (DDMS) is a rare epilepsy syndrome that is characterized by cerebral hemiatrophy, homolateral skull hyperplasia, hyperpneumatization of the paranasal sinuses, seizures with or without mental retardation, and contralateral hemiparesis. ", "Brain MRI showed prominent atrophy in the left frontal dorsal and lateral regions and mild atrophy of the left superior temporal gyrus and left parietal gyri.", "A 15-year-old female presented with seizures, right-sided hemiparesis, hemiatrophy of the right side of the body and mental retardation. ", "Described here is the case of a girl with a reticulated capillary malformation on the right side of her face, along with Dyke-Davidoff-Masson syndrome, as evidenced by microphthalmia and severe associated anomalies in the right eye, and right cerebral hemispheric atrophy and cerebral arteries malformations.", "The purpose of this study was to retrospectively evaluate the cognitive and electroclinical characteristics of right cerebral hemiatrophy (Dyke-Davidoff-Masson syndrome [DDMS]). ", "The CHA of childhood or Dyke-Davidoff-Masson syndrome, is originated by intrauterine or perinatal insults that affect the perfusion of a single cerebral hemisphere, manifesting clinically by variable mental retardation, refractory epilepsy, facial asymmetry, hemiplegia/hemiparesis or abnormal movements of the contralateral extremities and by imaging studies, loss of volume in one cerebral hemisphere and ipsilateral compensatory cranial changes such as skull vault thickening, elevation of the orbital roof and petreous ridge, also hyperpneumatization of the frontal sinus and mastoid cells.", "Dyke-Davidoff-Masson syndrome is a disorder involving hemiatrophy or hypoplasia of 1 cerebral hemisphere secondary to an insult in the developing brain. Often this will manifest with seizures, hemiparesis, mental retardation, and facial changes. Associated with this pathology are the radiologically evident changes, such as thickening of the calvarium, hyperpneumatization of the sinuses, and dilation of the ipsilateral lateral ventricle among others.", "Dyke-Davidoff-Masson syndrome, or cerebral hemiatrophy, is a pre- or perinatally acquired entity characterized by predominantly neurologic symptoms, such as seizures, facial asymmetry, contralateral hemiplegia, and mental retardation. ", "The Dyke-Davidoff-Masson syndrome is characterized by various symptoms related to hemiatrophy of the cerebrum and hypertrophy of the ipsilateral calvarium and paranasal sinuses. Clinical findings include hemiparesis or hemiplegia, seizures and/or mental retardation. ", "Asymmetry of cerebral hemispheric growth with atrophy on one side, ipsilateral osseous hypertrophy and hyper-pneumatization of sinuses with contralateral paresis are features of Dyke Davidoff Masson Syndrome (DDMS). ", "Dyke Davidoff Masson syndrome (DDMS) is characterized by seizures, facial asymmetry, contralateral hemiplegia and mental retardation. The characteristic radiologic features are cerebral hemiatrophy with homolateral hypertrophy of the skull and sinuses. We report a case of DDMS in an 18-month-old girl who presented with right sided focal seizures, hemiparesis of the same side, and delayed milestones.", "Cerebral hemiatrophy (Dyke-Davidoff-Masson syndrome) in childhood: clinicoradiological analysis of 19 cases.", "The so-called Dyke-Davidoff-Masson syndrome (DDMS) is a rare disorder of cerebral hemiatrophy. The clinical presentation may consist of facial asymmetry, contralateral atrophy (including the trunk, and the extremities) and hemiparesis, speech difficulties, mental retardation, and epilepsy.", "Dyke-Davidoff-Masson syndrome is clinically characterized by hemiparesis, hemiplegia, seizures, mental retardation, and facial asymmetry secondary to congenital or early childhood vascular insult. A 21-year-old man with Dyke-Davidoff-Masson syndrome presented with uncontrolled seizures.", "Dyke-Davidoff-Masson syndrome is a condition characterized by seizures, facial asymmetry, contralateral hemiplegia or hemiparesis and mental retardation.", "Brain MRI showed unilateral loss of cerebral volume with hypertrophy and hyperpneumatization of the paranasal sinuses and mastoid cells. ", "Although radiological findings of cerebral hemiatrophy (Dyke-Davidoff-Masson Syndrome) are well known, there is no systematic study about the gender and the affected side in this syndrome.", "The patient was a 19-year-old woman who presented with hemiatrophy and diminished superficial sensation on the left side of her body including her face. She had a past history of tonic-clonic seizures accompanied by left hemiparesis in late childhood. Brain CT demonstrated dilatation of the frontal sinus, calvarial thickening, cerebral hemiatrophy and dilatation of the lateral ventricle on the right side. Brain MRI showed atrophy of the right cerebrum and midbrain and dilatation of the lateral ventricle on T1-weighted images, as well as a high signal intensity area from the parietal to the occipital lobe on T2-weighted images. ", "Cerebral hemiatrophy or Dyke-Davidoff-Masson syndrome is a condition characterized by seizures, facial asymmetry, contralateral hemiplegia or hemiparesis, and mental retardation. ", "The radiological features are unilateral loss of cerebral volume and associated compensatory bone alterations in the calvarium, like thickening, hyperpneumatization of the paranasal sinuses and mastoid cells and elevation of the petrous ridge. ", "We reported a 39-year-old man with Dyke-Davidoff-Masson syndrome presenting with total hemiatrophy. ", "This paper presents an 18-year-old mentally retarded patient with cerebral hemiatrophy (Dyke-Davidoff-Masson syndrome) associated with a growing skull fracture in the ipsilateral hemicranium, in whom not only a dural tear but also the ipsilaterally displaced and dilated lateral ventricle due to the original disease apparently contributed to the development of growing skull fracture.", "The magnetic resonance (MR) findings of three patients with cerebral hemiatrophy, the so-called Dyke-Davidoff-Masson syndrome, which is characterized by variable degrees of unilateral loss of cerebral volume and compensatory changes of the calvarium are presented.", "MRI brain revealed characteristic features diagnostic of congenital type of cerebral hemiatrophy or Dyke-Davidoff-Masson syndrome.", "Imaging showed resolution of the infection and features of Dyke-Davidoff-Masson syndrome (cerebral hemiatrophy).", "Asymmetry of cerebral hemispheric growth with atrophy on one side, ipsilateral osseous hypertrophy and hyper-pneumatization of sinuses with contralateral paresis are features of Dyke Davidoff Masson Syndrome (DDMS).", "CT of the brain revealed characteristic features diagnostic of infantile type of cerebral hemiatrophy or Dyke-Davidoff-Masson syndrome", "Dyke-Davidoff-Masson syndrome refers to atrophy of one cerebral hemisphere (hemiatrophy) due to an insult to the brain in fetal or early childhood period", "Magnetic resonance imaging (MRI) of brain revealed atrophic of left cerebral hemisphere with mildly ventricular dilatation, prominent paranasal and mastoid air cells, suggestive of Dyke-Davidoff-Masson syndrome (DDMS)", "Dyke-Davidoff-Masson syndrome is a relatively rare syndrome with its typical clinical and radiological features including facial asymmetry, hemiplegia, cerebral hemiatrophy, mental retardation with calvarial thickening, hypertrophy of sinuses and elevated petrous ridge on imaging", "Dyke Davidoff Masson syndrome (DDMS) refers to atrophy or hypoplasia of one cerebral hemisphere following a prior fetal or childhood insult", "The purpose of this study was to retrospectively evaluate the cognitive and electroclinical characteristics of right cerebral hemiatrophy (Dyke-Davidoff-Masson syndrome [DDMS])", "We describe a female infant with prenatal diagnosis of unilateral left ventriculomegaly in which early brain MRI and contrast enhanced-MRI angiography, showed cerebral left hemiatrophy associated with reduced caliber of the left middle cerebral artery revealing the characteristic findings of the Dyke-Davidoff-Masson syndrome" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/25207154", "http://www.ncbi.nlm.nih.gov/pubmed/23672850", "http://www.ncbi.nlm.nih.gov/pubmed/20691943", "http://www.ncbi.nlm.nih.gov/pubmed/21764333", "http://www.ncbi.nlm.nih.gov/pubmed/15869006", "http://www.ncbi.nlm.nih.gov/pubmed/7761171", "http://www.ncbi.nlm.nih.gov/pubmed/7214933", "http://www.ncbi.nlm.nih.gov/pubmed/15158218", "http://www.ncbi.nlm.nih.gov/pubmed/19204321", "http://www.ncbi.nlm.nih.gov/pubmed/23591309", "http://www.ncbi.nlm.nih.gov/pubmed/10029885", "http://www.ncbi.nlm.nih.gov/pubmed/22967682", "http://www.ncbi.nlm.nih.gov/pubmed/20236868", "http://www.ncbi.nlm.nih.gov/pubmed/23189018", "http://www.ncbi.nlm.nih.gov/pubmed/17250509", "http://www.ncbi.nlm.nih.gov/pubmed/24419451", "http://www.ncbi.nlm.nih.gov/pubmed/12763349", "http://www.ncbi.nlm.nih.gov/pubmed/19744394", "http://www.ncbi.nlm.nih.gov/pubmed/11814746", "http://www.ncbi.nlm.nih.gov/pubmed/21559157", "http://www.ncbi.nlm.nih.gov/pubmed/24891488", "http://www.ncbi.nlm.nih.gov/pubmed/1547482", "http://www.ncbi.nlm.nih.gov/pubmed/16100487", "http://www.ncbi.nlm.nih.gov/pubmed/15798614", "http://www.ncbi.nlm.nih.gov/pubmed/8997138", "http://www.ncbi.nlm.nih.gov/pubmed/23344879", "http://www.ncbi.nlm.nih.gov/pubmed/19029569", "http://www.ncbi.nlm.nih.gov/pubmed/19169186", "http://www.ncbi.nlm.nih.gov/pubmed/24257011", "http://www.ncbi.nlm.nih.gov/pubmed/22681314", "http://www.ncbi.nlm.nih.gov/pubmed/19097769", "http://www.ncbi.nlm.nih.gov/pubmed/24977128" ]

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[ "Tafazzin is a mitochondrial phospholipid transacylase, and its mutations cause Barth syndrome (BTHS)", "Tafazzin, a mitochondrial acyltransferase encoded by a gene of the same name, plays an important role in cardiolipin side chain remodeling. Studies have shown that mutation-induced dysfunction of tafazzin reduces cardiolipin content, impairs mitochondrial function, and causes dilated cardiomyopathy in Barth syndrome (BTHS)." ]

[ "Tafazzin (TAZ) gene" ]

[ "Tafazzin is a mitochondrial phospholipid transacylase, and its mutations cause Barth syndrome (BTHS)", "Tafazzin, a mitochondrial acyltransferase, plays an important role in cardiolipin side chain remodeling. Previous studies have shown that dysfunction of tafazzin reduces cardiolipin content, impairs mitochondrial function, and causes dilated cardiomyopathy in Barth syndrome", "we combined patient-derived and genetically engineered induced pluripotent stem cells (iPSCs) with tissue engineering to elucidate the pathophysiology underlying the cardiomyopathy of Barth syndrome (BTHS), a mitochondrial disorder caused by mutation of the gene encoding tafazzin (TAZ)", "A zebrafish model of human Barth syndrome reveals the essential role of tafazzin in cardiac development and function.", "Barth syndrome: cellular compensation of mitochondrial dysfunction and apoptosis inhibition due to changes in cardiolipin remodeling linked to tafazzin (TAZ) gene mutation.", "This resynthesis of deacylated cardiolipin from monolysocardiolipin occurs via the Barth Syndrome gene product tafazzin and acyllysocardiolipin acyltransferase-1, monolysocardiolipin acyltransferase-1 and the alpha subunit of trifunctional protein.", "We conclude that mitochondria-targeted antioxidant prevents cardiac dysfunction induced by tafazzin gene knockdown in cardiac myocytes and suggest mito-Tempo as a potential therapeutic for Barth syndrome and other dilated cardiomyopathies resulting from mitochondrial oxidative stress.", "Here, we combined patient-derived and genetically engineered induced pluripotent stem cells (iPSCs) with tissue engineering to elucidate the pathophysiology underlying the cardiomyopathy of Barth syndrome (BTHS), a mitochondrial disorder caused by mutation of the gene encoding tafazzin (TAZ).", "Mutations in the human TAZ gene are associated with Barth Syndrome, an often fatal X-linked disorder that presents with cardiomyopathy and neutropenia.", "A Novel TAZ Gene Mutation and Mosaicism in a Polish Family with Barth Syndrome", "Barth syndrome: cellular compensation of mitochondrial dysfunction and apoptosis inhibition due to changes in cardiolipin remodeling linked to tafazzin (TAZ) gene mutation", "Barth syndrome is caused by mutations in the TAZ (tafazzin) gene on human chromosome Xq28", "BTHS is caused by loss-of-function mutations of the tafazzin (TAZ) gene. ", "This abnormality involves the deletion of the bases TGA starting at cDNA nucleotide 891 (c891_893delTGA), resulting in the absence of glutamic acid at codon 202 from a highly conserved area of the tafazzin protein, consistent with the diagnosis of Barth syndrome. ", "Novel mutations in the TAZ gene in patients with Barth syndrome.", "A zebrafish model of human Barth syndrome reveals the essential role of tafazzin in cardiac development and function.", "The Barth Syndrome gene TAZ has been identified and expression of the gene yields proteins known as tafazzins." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/20981509", "http://www.ncbi.nlm.nih.gov/pubmed/24342716", "http://www.ncbi.nlm.nih.gov/pubmed/23523468", "http://www.ncbi.nlm.nih.gov/pubmed/24813252", "http://www.ncbi.nlm.nih.gov/pubmed/24093814", "http://www.ncbi.nlm.nih.gov/pubmed/24801725", "http://www.ncbi.nlm.nih.gov/pubmed/25941633", "http://www.ncbi.nlm.nih.gov/pubmed/16857210", "http://www.ncbi.nlm.nih.gov/pubmed/22023389", "http://www.ncbi.nlm.nih.gov/pubmed/16442164", "http://www.ncbi.nlm.nih.gov/pubmed/16794186", "http://www.ncbi.nlm.nih.gov/pubmed/25247053", "http://www.ncbi.nlm.nih.gov/pubmed/25776009" ]

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[ "Common treatment of subacute thyroiditis is with anti-inflammatory drug agents, namely corticosteroids" ]

[]

[ "Oral glucocorticoids are administered in moderate and severe cases of subacute thyroiditis (SAT)", "he treatment protocol that we employed had 15 mg/day of PSL as the initial dosage for the treatment of SAT, with tapering by 5 mg every 2 weeks" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/17923793", "http://www.ncbi.nlm.nih.gov/pubmed/23227861", "http://www.ncbi.nlm.nih.gov/pubmed/22313427", "http://www.ncbi.nlm.nih.gov/pubmed/22138076" ]

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[ "http://www.disease-ontology.org/api/metadata/DOID:7187", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004364", "http://www.disease-ontology.org/api/metadata/DOID:7166", "http://www.disease-ontology.org/api/metadata/DOID:7165", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013959", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0042493", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013968", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013956" ]

[ "BMAL1 deficiency is associated with premature aging and reduced lifespan and BMAL1 deficiency leads to development of stress induced senescence in vivo. Down-regulation of Bmal1 also accelerates the development of tumours, adipogenesis." ]

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[ "BMAL1 deficiency is associated with premature aging and reduced lifespan", "BMAL1 deficiency leads to development of stress induced senescence in vivo.", " Down-regulation of Bmal1 accelerates the development of tumours ", "BMAL1 deficiency results in premature aging in mice", "BMAL1 deficiency disrupts circadian oscillation in gene expression and reactive oxygen species homeostasis in the brain,", "We demonstrate that attenuation of Bmal1 function resulted in down-regulation of genes in the canonical Wnt pathway, known to suppress adipogenesis. " ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/22611086", "http://www.ncbi.nlm.nih.gov/pubmed/24481314", "http://www.ncbi.nlm.nih.gov/pubmed/20576619", "http://www.ncbi.nlm.nih.gov/pubmed/21149897", "http://www.ncbi.nlm.nih.gov/pubmed/22101268", "http://www.ncbi.nlm.nih.gov/pubmed/20519775" ]

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[ "A member of the polycomb repressive complex 2 (PRC2) directly mediates the addition of K27me3 to histone H3, a modification associated with heterochromatin, and it is believed that this activity mediates transcriptional repression. At the same time PRC2 activity results in a global increase in H3K27 acetylation. Some members of the PcG display affinity towards both histone H3 trimethylated at K9 and H3K27me3, and one CD prefers K9me3." ]

[ "H3K27me3", "H3K27Ac", "H3K9me3", "H3K36me" ]

[ "The PcG proteins are well-conserved chromatin factors that repress transcription of numerous target genes. They bind the genome at specific sites, forming chromatin domains of associated histone modifications as well as higher-order chromatin structures.", "A component of Polycomb repressive complex 2 (PRC2), which mediates the addition of K27me3 to histone H3 (Suz12), was also recruited by 14 dpi", "We found that a component of the PRC1 complex (Bmi1), which binds to H3K27me3, was not enriched at promoters found previously to be enriched for H3K27me3", " Here we show that the HSV DNA first associates with histone H3, with later recruitment of Polycomb repressor complex 2 (PRC2) and trimethylation of the lysine 27 residue of histone H3 (H3K27me3), a modification associated with heterochromatin", "Here we show that direct recognition of methylated histone H3 Lys36 (H3K36me), a mark associated with activation, by the PRC2 subunit Phf19 is required for the full enzymatic activity of the PRC2 complex", "Furthermore, we show that Phf19 binds to a subset of PRC2 targets in mouse embryonic stem cells and that this is required for their repression and for H3K27me3 deposition", "The Polycomb repressive complex 2 (PRC2) catalyzes trimethylation (me3) of histone H3 lysine 27 (K27), and it is believed that this activity mediates transcriptional repression", "We show that loss of PRC2 activity results in a global increase in H3K27 acetylation", "Moreover, we provide evidence that the acetylation of H3K27 is catalyzed by the acetyltransferases p300 and CBP.", "Taken together, these studies suggest that patterns of epigenetic modifiers and the histone code influence the propensity of a gene to become hypermethylated in cancer and that DNMT3B plays an important role in regulating PRC1 function", "During differentiation, binding of polycomb repressive complex 2 (PRC2), which mediates trimethylation of lysine 27 on histone H3 (K27me3), is lost on developmental genes that are transcriptionally induced", "chromodomain (CD) of the Drosophila Polycomb protein exhibits preferential binding affinity for histone H3 when trimethylated at lysine 27", "Not all CDs bind preferentially to K27me3; rather, some display affinity towards both histone H3 trimethylated at K9 and H3K27me3, and one CD prefers K9me3" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/23694722", "http://www.ncbi.nlm.nih.gov/pubmed/19723660", "http://www.ncbi.nlm.nih.gov/pubmed/23322639", "http://www.ncbi.nlm.nih.gov/pubmed/20385584", "http://www.ncbi.nlm.nih.gov/pubmed/16537902", "http://www.ncbi.nlm.nih.gov/pubmed/17525233", "http://www.ncbi.nlm.nih.gov/pubmed/23104054" ]

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[ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0031519", "http://www.biosemantics.org/jochem#4278518", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D063146", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0016573", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0016570", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0016571", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D006657", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0035102" ]

[ "CLIC1 is an intracellular chloride ion channel that is localized both to the nucleus and to the cytolasm." ]

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[ "CLIC1 expression was obtained in the cytoplasm and plasma membrane of cells in both cell lines.", "CLIC1, an intracellular chloride ion channel,", "Like NCC27/CLIC1, CLIC3 is predominantly localized in the nucleus ", "the nuclear localization pattern of CLIC1 was remarkably changed by insulin stimulation" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/21055175", "http://www.ncbi.nlm.nih.gov/pubmed/15827065", "http://www.ncbi.nlm.nih.gov/pubmed/9880541" ]

[ { "p": "http://purl.uniprot.org/core/encodedBy", "s": "http://purl.uniprot.org/uniprot/Q5E9B7", "o": "http://linkedlifedata.com/resource/#_51354539423700E" }, { "p": "http://www.w3.org/2004/02/skos/core#prefLabel", "s": "http://linkedlifedata.com/resource/#_51354539423700E", "o": "CLIC1" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_51354539423700C", "o": "Chloride intracellular channel protein 1" }, { "p": "http://purl.uniprot.org/core/encodedBy", "s": "http://purl.uniprot.org/uniprot/Q95MF9", "o": "http://linkedlifedata.com/resource/#_5139354D463900A" }, { "p": "http://www.w3.org/2004/02/skos/core#prefLabel", "s": "http://linkedlifedata.com/resource/#_5139354D463900A", "o": "CLIC1" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_5139354D4639009", "o": "Chloride intracellular channel protein 1" } ]

[ "http://www.uniprot.org/uniprot/CLIC1_MOUSE", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0008104", "http://www.uniprot.org/uniprot/CLIC1_RAT", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0051234", "http://www.uniprot.org/uniprot/CLIC1_PIG", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0051179", "http://www.uniprot.org/uniprot/CLIC1_HUMAN", "http://www.uniprot.org/uniprot/CLIC1_RABIT", "http://www.uniprot.org/uniprot/CLIC1_BOVIN" ]

[ "The most common consensus motifs for CK1 are: pSer-Xaa-Xaa-Ser, K/R-X-K/R-X-X-S/T, SLS and acidic cluster motifs and SerP/ThrP-Xaa-Xaa-Ser/Thr." ]

[ "pSer-Xaa-Xaa-Ser", "K/R-X-K/R-X-X-S/T", "SLS and acidic cluster motifs", "SerP/ThrP-Xaa-Xaa-Ser/Thr" ]

[ "Members of the protein kinase CK1 family usually phosphorylate residues of serine that are close to other phosphoserine in a consensus motif of pS-X-X-S,", "a novel consensus phosphorylation motif (K/R-X-K/R-X-X-S/T) for CK1 ", "CK1 acts as a 'phosphate-directed' kinase whose targeting is primed by a single phosphorylated side chain at position n-3 or n-4 relative to serine/threonine", "The protein kinase CK1 phosphorylates serine residues that are located close to another phosphoserine in the consensus pSer-Xaa-Xaa-Ser.", "The results demonstrate that SLS and acidic cluster motifs are crucial for CK1 recognition. ", "The common features include an SLS motif followed two to five residues downstream by a cluster of acidic residues.", "These data provide the clear-cut demonstration that the consensus sequence with N-terminal prephosphorylated residue(s), SerP/ThrP-Xaa-Xaa-Ser/Thr" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/8055935", "http://www.ncbi.nlm.nih.gov/pubmed/18239272", "http://www.ncbi.nlm.nih.gov/pubmed/15975091", "http://www.ncbi.nlm.nih.gov/pubmed/12925738", "http://www.ncbi.nlm.nih.gov/pubmed/11781102", "http://www.ncbi.nlm.nih.gov/pubmed/14710188", "http://www.ncbi.nlm.nih.gov/pubmed/18799313" ]

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[ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D010766", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D047389", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0016310", "http://www.uniprot.org/uniprot/KC1A_RAT", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0042327", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D032921", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016384", "http://www.uniprot.org/uniprot/KC1_PLAF7", "http://www.uniprot.org/uniprot/KC1A_CAEEL", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0042325", "http://www.uniprot.org/uniprot/KC1A_HUMAN", "http://www.uniprot.org/uniprot/KC1AL_HUMAN" ]

[ "ROCKET-AF trial compared rivaroxaban and warfarin for for prevention of stroke and embolism." ]

[ "rivaroxaban", "warfarin" ]

[ "METHODS AND RESULTS: Patients randomized in the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET-AF) trial (n = 14 264) were grouped by baseline AF category: paroxysmal or persistent. Multivariable adjustment was performed to compare thrombo-embolic events, bleeding, and death between groups, in high-risk subgroups, and across treatment assignment (rivaroxaban or warfarin). ", "This review focuses on the direct Factor Xa inhibitor rivaroxaban, summarizing the properties that make rivaroxaban appropriate for anticoagulant therapy in this indication (including its predictable pharmacokinetic and pharmacodynamic profile and once-daily dosing regimen) and describing data from the Phase III ROCKET AF trial, which showed once-daily rivaroxaban to be noninferior to warfarin for the prevention of stroke in patients with nonvalvular AF.", "Subanalyses of ROCKET AF data showed rivaroxaban to have consistent efficacy and safety across a wide range of patients, and studies to confirm these results in real-world settings are underway. ", "Rivaroxaban for stroke prevention in East Asian patients from the ROCKET AF trial.", "CONCLUSIONS: Observed relative efficacy and safety of rivaroxaban versus warfarin were similar among patients within and outside East Asia. ", "Rivaroxaban versus warfarin in Japanese patients with nonvalvular atrial fibrillation in relation to the CHADS2 score: a subgroup analysis of the J-ROCKET AF trial.", "BACKGROUND: Results from a trial of rivaroxaban versus warfarin in 1280 Japanese patients with atrial fibrillation (J-ROCKET AF) revealed that rivaroxaban was noninferior to warfarin with respect to the principal safety outcome. ", "Rivaroxaban, an oral direct factor Xa-inhibitor was non-inferior to adjusted dose warfarin in the prevention of stroke and embolism among patients with atrial fibrillation (AF) in the ROCKET-AF trial and has been approved for stroke prevention in AF.", "The ROCKET AF trial compared rivaroxaban (20 mg/day; 15 mg/day in patients with creatinine clearance 30-49 ml/min) with dose-adjusted warfarin (international normalized ratio 2-3) in 14,264 patients with AF and a prior history of stroke or at least two other additional risk factors for stroke.", "Factors associated with major bleeding events: insights from the ROCKET AF trial (rivaroxaban once-daily oral direct factor Xa inhibition compared with vitamin K antagonism for prevention of stroke and embolism trial in atrial fibrillation).", "In Rivaroxaban Once Daily Oral Direct Factor Xa Inhibitor Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF) trial, rivaroxaban was noninferior to dose-adjusted warfarin in preventing stroke or systemic embolism among patients with nonvalvular atrial fibrillation at moderate to high stroke risk.", "Different clinical trials have shown the benefits of new oral anticoagulants over warfarin, but patients included in the ROCKET-AF trial were found to be at a higher risk of AF-related complications.", "The ROCKET AF trial demonstrated the noninferiority of rivaroxaban compared with warfarin for the prevention of stroke and systemic embolism, with a similar rate of major bleeding and a substantial reduction in intracranial hemorrhage.", "Rivaroxaban for stroke prevention in atrial fibrillation: a critical review of the ROCKET AF trial.", "Outcomes after cardioversion and atrial fibrillation ablation in patients treated with rivaroxaban and warfarin in the ROCKET AF trial.", "The overall analysis of the rivaroxaban versus warfarin in Japanese patients with atrial fibrillation (J-ROCKET AF) trial revealed that rivaroxaban was not inferior to warfarin with respect to the primary safety outcome.", "Medical costs in the US of clinical events associated with oral anticoagulant (OAC) use compared to warfarin among non-valvular atrial fibrillation patients ≥75 and <75 years of age, based on the ARISTOTLE, RE-LY, and ROCKET-AF trials.", "In patients at risk of stroke due to atrial fibrillation, rivaroxaban was noninferior compared to warfarin in preventing stroke/systemic embolism in the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET-AF) trial and was associated with a similar risk of major bleeding; the incidence of intracranial hemorrhage was 33% lower with rivaroxaban", "Outcomes of discontinuing rivaroxaban compared with warfarin in patients with nonvalvular atrial fibrillation: analysis from the ROCKET AF trial (Rivaroxaban Once-Daily, Oral, Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation)", "The Phase III ROCKET AF (Rivaroxaban Once-Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation) trial showed that rivaroxaban, an oral, direct Factor Xa inhibitor, was noninferior to warfarin for the reduction of stroke or systemic embolism in patients with AF", "In Rivaroxaban Once Daily Oral Direct Factor Xa Inhibitor Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF) trial, rivaroxaban was noninferior to dose-adjusted warfarin in preventing stroke or systemic embolism among patients with nonvalvular atrial fibrillation at moderate to high stroke risk", "We investigated clinical characteristics and outcomes of patients with significant valvular disease (SVD) in the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF) trial", "Efficacy and safety of rivaroxaban compared with warfarin among elderly patients with nonvalvular atrial fibrillation in the Rivaroxaban Once Daily, Oral, Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF)", "The oral factor Xa inhibitor rivaroxaban was noninferior to warfarin in the Rivaroxaban Once Daily, Oral, Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF)", "We studied the use and outcomes of digoxin in patients in the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF)", "Outcomes of discontinuing rivaroxaban compared with warfarin in patients with nonvalvular atrial fibrillation: analysis from the ROCKET AF trial (Rivaroxaban Once-Daily, Oral, Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation).", "Relationship between time in therapeutic range and comparative treatment effect of rivaroxaban and warfarin: results from the ROCKET AF trial.", "Efficacy and safety of rivaroxaban compared with warfarin among elderly patients with nonvalvular atrial fibrillation in the Rivaroxaban Once Daily, Oral, Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF).", "Outcomes of temporary interruption of rivaroxaban compared with warfarin in patients with nonvalvular atrial fibrillation: results from the rivaroxaban once daily, oral, direct factor Xa inhibition compared with vitamin K antagonism for prevention of stroke and embolism trial in atrial fibrillation (ROCKET AF).", " Health care providers should consider renal function, concomitant medication, polymorbidity and age prior to prescribing rivaroxaban. Care has to be taken when prescribing rivaroxaban to patients who are different from those included in the ROCKET AF trial.", "Health care providers should consider renal function, concomitant medication, polymorbidity and age prior to prescribing rivaroxaban. Care has to be taken when prescribing rivaroxaban to patients who are different from those included in the ROCKET AF trial.", "A separate trial, J-ROCKET AF, compared the safety of a Japan-specific rivaroxaban dose with warfarin administered according to Japanese guidelines in Japanese patients with AF.J-ROCKET AF was a prospective, randomized, double-blind, phase III trial.", "A separate trial, J-ROCKET AF, compared the safety of a Japan-specific rivaroxaban dose with warfarin administered according to Japanese guidelines in Japanese patients with AF. J-ROCKET AF was a prospective, randomized, double-blind, phase III trial." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/23352688", "http://www.ncbi.nlm.nih.gov/pubmed/22664783", "http://www.ncbi.nlm.nih.gov/pubmed/24659084", "http://www.ncbi.nlm.nih.gov/pubmed/24895454", "http://www.ncbi.nlm.nih.gov/pubmed/24763930", "http://www.ncbi.nlm.nih.gov/pubmed/24794785", "http://www.ncbi.nlm.nih.gov/pubmed/24755148", "http://www.ncbi.nlm.nih.gov/pubmed/25148838", "http://www.ncbi.nlm.nih.gov/pubmed/23405833", "http://www.ncbi.nlm.nih.gov/pubmed/25083135", "http://www.ncbi.nlm.nih.gov/pubmed/24552831", "http://www.ncbi.nlm.nih.gov/pubmed/25209598", "http://www.ncbi.nlm.nih.gov/pubmed/23954611", "http://www.ncbi.nlm.nih.gov/pubmed/23391196", "http://www.ncbi.nlm.nih.gov/pubmed/24315894", "http://www.ncbi.nlm.nih.gov/pubmed/25749644", "http://www.ncbi.nlm.nih.gov/pubmed/23869941", "http://www.ncbi.nlm.nih.gov/pubmed/23030284", "http://www.ncbi.nlm.nih.gov/pubmed/24711702", "http://www.ncbi.nlm.nih.gov/pubmed/23500298" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016449", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016032", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016430", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D002986" ]

[ "The rapid accumulation of knowledge on biological signaling pathways and their regulatory mechanisms has highlighted the need for specific repositories that can store, organize and allow retrieval of pathway information in a way that will be useful for the research community. SPIKE (Signaling Pathways Integrated Knowledge Engine; http://www.cs.tau.ac.il/&~spike/) is a database for achieving this goal, containing highly curated interactions for particular human pathways, along with literature-referenced information on the nature of each interaction. To make database population and pathway comprehension straightforward, a simple yet informative data model is used, and pathways are laid out as maps that reflect the curator’s understanding and make the utilization of the pathways easy. The database currently focuses primarily on pathways describing DNA damage response, cell cycle, programmed cell death and hearing related pathways. Pathways are regularly updated, and additional pathways are gradually added. The complete database and the individual maps are freely exportable in several formats. The database is accompanied by a stand-alone software tool for analysis and dynamic visualization of pathways." ]

[]

[ "The rapid accumulation of knowledge on biological signaling pathways and their regulatory mechanisms has highlighted the need for specific repositories that can store, organize and allow retrieval of pathway information in a way that will be useful for the research community. SPIKE (Signaling Pathways Integrated Knowledge Engine; http://www.cs.tau.ac.il/&~spike/) is a database for achieving this goal, containing highly curated interactions for particular human pathways, along with literature-referenced information on the nature of each interaction. To make database population and pathway comprehension straightforward, a simple yet informative data model is used, and pathways are laid out as maps that reflect the curator’s understanding and make the utilization of the pathways easy. The database currently focuses primarily on pathways describing DNA damage response, cell cycle, programmed cell death and hearing related pathways. Pathways are regularly updated, and additional pathways are gradually added. The complete database and the individual maps are freely exportable in several formats. The database is accompanied by a stand-alone software tool for analysis and dynamic visualization of pathways.", "SPIKE: a database of highly curated human signaling pathways.", "SPIKE (Signaling Pathways Integrated Knowledge Engine; http://www.cs.tau.ac.il/&~spike/) is a database for achieving this goal, containing highly curated interactions for particular human pathways, along with literature-referenced information on the nature of each interaction.", "SPIKE--a database, visualization and analysis tool of cellular signaling pathways.", "SPIKE (Signaling Pathways Integrated Knowledge Engine; http://www.cs.tau.ac.il/&~spike/) is a database for achieving this goal, containing highly curated interactions for particular human pathways, along with literature-referenced information on the nature of each interaction. ", "SPIKE (Signaling Pathways Integrated Knowledge Engine; http://www.cs.tau.ac.il/&amp;~spike/) is a database for achieving this goal, containing highly curated interactions for particular human pathways, along with literature-referenced information on the nature of each interaction." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/21097778", "http://www.ncbi.nlm.nih.gov/pubmed/18289391" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D015398", "http://amigo.geneontology.org/amigo/term/GO:0007165", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D019991" ]

[ "Yes, The Dictyostelium discoideum genome has been sequenced, assembled and annotated to a high degree of reliability. The parts-list of proteins and RNA encoded by the six chromosomes can now be accessed and analyzed. Consequently, this genomic sequence information can now be exploited to realize D. discoideum proteomics projects." ]

[ "yes" ]

[ "The Negative Proteome Database (NPD) is populated with pair-wise protein sequence comparisons between each of the following proteomes: Homo sapiens, Mus musculus, Drosophila melanogaster, Caenorhabditis elegans, Saccharomyces cerevisiae, Dictyostelium discoideum, Chlamydomonus reinhardti, Escherichia coli K12, Arabidopsis thaliana and Methanoscarcina acetivorans.", "The Dictyostelium discoideum proteome--the SWISS-2DPAGE database of the multicellular aggregate (slug).", "Consequently, this genomic sequence information can now be exploited to realize D. discoideum proteomics projects. ", "The Dictyostelium discoideum genome has been sequenced, assembled and annotated to a high degree of reliability. The parts-list of proteins and RNA encoded by the six chromosomes can now be accessed and analyzed. ", "The 34 Mb genome of Dictyostelium discoideum is carried on 6 chromosomes and has been fully sequenced by an international consortium. The sequence was assembled on the classical and physical maps that had been built up over the years and refined by HAPPY mapping. Annotation of the sequence predicted about 12,000 genes for proteins of at least 50 amino acids in length.", "In this study, a quantitative comparative proteomics approach has been used to analyze the Dictyostelium discoideum mitochondrial proteome variations during vegetative growth, starvation and the early stages of development. ", "The secreted proteome profile of developing Dictyostelium discoideum cells.", "The present repertoire validates our purification method and paves the way for a future proteomics approach to study the dynamics of macropinocytosis.", "Proteomic analysis of a developmentally regulated secretory vesicle." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/16875414", "http://www.ncbi.nlm.nih.gov/pubmed/20013782", "http://www.ncbi.nlm.nih.gov/pubmed/20422638", "http://www.ncbi.nlm.nih.gov/pubmed/16957282", "http://www.ncbi.nlm.nih.gov/pubmed/22120990", "http://www.ncbi.nlm.nih.gov/pubmed/16957286", "http://www.ncbi.nlm.nih.gov/pubmed/18820470", "http://www.ncbi.nlm.nih.gov/pubmed/9150929", "http://www.ncbi.nlm.nih.gov/pubmed/11990506" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D040901", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D020543", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004023" ]

[ "perilipins\nadipose differentiation-related protein\nlipid storage droplet protein 5 \ntail-interacting protein of 47 kilodaltons \nS3-12" ]

[ "perilipins", "adipose differentiation-related protein", "ADFP", "LSDP5", "lipid storage droplet protein 5", "tail-interacting protein of 47 kilodaltons", "TIP47", "S3-12" ]

[ "The perilipins are a multi-protein family that targets lipid droplet surfaces and regulates lipid storage and hydrolysis.", "or the abundance of the lipid droplet coat proteins (perilipins 2, 3, 4, and 5) between treatments. ", "This study investigated the lipid droplet coat proteins perilipin 1 (PLIN1) and perilipin 2 (PLIN2) localization in pig skeletal muscle and their relationship with intramuscular fat (IMF) content.", "Lipid droplets of mammalian cells are coated with one or more members of the PAT protein family, which serve important functions in regulating lipolysis. In this study, we investigate the mechanisms by which PAT family members, perilipin A, adipose differentiation-related protein (ADFP), and LSDP5, control lipolysis catalyzed by hormone-sensitive lipase (HSL), a major lipase in adipocytes and several non-adipose cells.", "The coordination of lipid storage and utilization is regulated by the perilipin family of lipid droplet coat proteins [perilipin, adipophilin/adipocyte differentiation-related protein (ADRP), S3-12, tail-interacting protein of 47 kilodaltons (TIP47), and myocardial lipid droplet protein (MLDP)/oxidative tissues-enriched PAT protein (OXPAT)/lipid storage droplet protein 5 (LSDP5)].", " Perilipin is a member of the evolutionarily related family of PAT proteins (Perilipin, Adipophilin, TIP47), which is defined by sequence similarity and association with lipid droplets. " ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/23204327", "http://www.ncbi.nlm.nih.gov/pubmed/18202123", "http://www.ncbi.nlm.nih.gov/pubmed/21420243", "http://www.ncbi.nlm.nih.gov/pubmed/24036367", "http://www.ncbi.nlm.nih.gov/pubmed/19717842", "http://www.ncbi.nlm.nih.gov/pubmed/19748893", "http://www.ncbi.nlm.nih.gov/pubmed/15731108", "http://www.ncbi.nlm.nih.gov/pubmed/20870251" ]

[ { "p": "http://purl.uniprot.org/core/mnemonic", "s": "http://purl.uniprot.org/uniprot/O60240", "o": "PLIN1_HUMAN" }, { "p": "http://purl.uniprot.org/core/recommendedName", "s": "http://purl.uniprot.org/uniprot/O60240", "o": "http://linkedlifedata.com/resource/#_4F363032343000B" }, { "p": "http://purl.uniprot.org/core/alternativeName", "s": "http://purl.uniprot.org/uniprot/O60240", "o": "http://linkedlifedata.com/resource/#_4F363032343000C" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_4F363032343000B", "o": "Perilipin-1" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_4F363032343000C", "o": "Lipid droplet-associated protein" }, { "p": "http://purl.uniprot.org/core/mnemonic", "s": "http://purl.uniprot.org/uniprot/P43884", "o": "PLIN_RAT" }, { "p": "http://purl.uniprot.org/core/alternativeName", "s": "http://purl.uniprot.org/uniprot/P43884", "o": "http://linkedlifedata.com/resource/#_503433383834009" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_503433383834009", "o": "Lipid droplet-associated protein" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_503433383834008", "o": "Perilipin-1" }, { "p": "http://purl.uniprot.org/core/recommendedName", "s": "http://purl.uniprot.org/uniprot/P43884", "o": "http://linkedlifedata.com/resource/#_503433383834008" }, { "p": "http://purl.uniprot.org/core/mnemonic", "s": "http://purl.uniprot.org/uniprot/P43884", "o": "PERL_RAT" } ]

[]

[ "The Barr body is the inactive X chromosome in a female somatic cell. It is readily identified as plano-convex structure of 2-3 micron in diameter on the periphery of the nuclear membrane. One of the X-chromosomes by a random inactivation process condenses to form X-chromatin (Barr body) in early embryonic life. Once this occurs, it is final and fixed for that cell and all its descendants (1,2). Barr body is an inactivated X chromosome in the normal female somatic cell. Inactivation of these chromosomes is known as Lyonization. Lyonization has both genetic and clinical significance. Barr body can be easily identified with ordinary stains. It also helps in identifying the sex of an individual when used judiciously. The Barr body has long been recognized as the cytological manifestation of the inactive X chromosome (Xi) in interphase nuclei. Despite being known for over 50 years, relatively few components of the Barr body have been identified. ", "The Barr body is the inactive X chromosome in a female somatic cell.", "The Barr body is the inactive X chromosome in a female somatic cell. It is readily identified as plano-convex structure of 2-3 micron in diameter on the periphery of the nuclear membrane. One of the X-chromosomes by a random inactivation process condenses to form X-chromatin (Barr body) in early embryonic life. Once this occurs, it is final and fixed for that cell and all its descendants (1,2). ", "The Barr body is the inactive X chromosome in a female somatic cell. It is readily identified as plano-convex structure of 2-3 micron in diameter on the periphery of the nuclear membrane. One of the X-chromosomes by a random inactivation process condenses to form X-chromatin (Barr body) in early embryonic life. Once this occurs, it is final and fixed for that cell and all its descendants (1,2). The Barr body has long been recognized as the cytological manifestation of the inactive X chromosome (Xi) in interphase nuclei. Despite being known for over 50 years, relatively few components of the Barr body have been identified. ", "In the late 1940s, a microanatomist from London Ontario, Murray Barr, discovered a mark of sex chromosome status in bodily tissues, what came to be known as the 'Barr body'. The Barr body is the inactive X chromosome in a female somatic cell. It is readily identified as plano-convex structure of 2-3 micron in diameter on the periphery of the nuclear membrane. One of the X-chromosomes by a random inactivation process condenses to form X-chromatin (Barr body) in early embryonic life. Once this occurs, it is final and fixed for that cell and all its descendants. Inactivation of these chromosomes is known as Lyonization. Lyonization has both genetic and clinical significance. Barr body can be easily identified with ordinary stains. It also helps in identifying the sex of an individual when used judiciously. Despite being known for over 50 years, relatively few components of the Barr body have been identified. The Barr body, is enriched in repressive histone modifications such as trimethylation of histone H3 Lys9 (H3K9me3) and Lys27 (H3K27me3). However, numerous investigators have observed extreme variations in Barr body frequency in tumour cells." ]

[]

[ "The Barr body is the inactive X chromosome in a female somatic cell. It is readily identified as plano-convex structure of 2-3 micron in diameter on the periphery of the nuclear membrane. ", "Human inactive X chromosome (Xi) forms a compact structure called the Barr body, which is enriched in repressive histone modifications such as trimethylation of histone H3 Lys9 (H3K9me3) and Lys27 (H3K27me3). ", "In the late 1940s, a microanatomist from London Ontario, Murray Barr, discovered a mark of sex chromosome status in bodily tissues, what came to be known as the 'Barr body'. This discovery offered an important diagnostic technology to the burgeoning clinical science community engaged with the medical interpretation and management of sexual anomalies.", "Barr body is an inactivated X chromosome in the normal female somatic cell. Inactivation of these chromosomes is known as Lyonization. Lyonization has both genetic and clinical significance. Barr body can be easily identified with ordinary stains. It also helps in identifying the sex of an individual when used judiciously. ", "The Barr body has long been recognized as the cytological manifestation of the inactive X chromosome (Xi) in interphase nuclei. Despite being known for over 50 years, relatively few components of the Barr body have been identified.", "One of the X-chromosomes by a random inactivation process condenses to form X-chromatin (Barr body) in early embryonic life. Once this occurs, it is final and fixed for that cell and all its descendants (1,2).", "However, numerous investigators have observed extreme variations in Barr body frequency in tumour cells. ", "Human inactive X chromosome (Xi) forms a compact structure called the Barr body, which is enriched in repressive histone modifications such as trimethylation of histone H3 Lys9 (H3K9me3) and Lys27 (H3K27me3).", "The Barr body is the inactive X chromosome in a female somatic cell", "Barr body is an inactivated X chromosome in the normal female somatic cell. ", "In the late 1940s, a microanatomist from London Ontario, Murray Barr, discovered a mark of sex chromosome status in bodily tissues, what came to be known as the 'Barr body'. ", "The Barr body has long been recognized as the cytological manifestation of the inactive X chromosome (Xi) in interphase nuclei.", "One of the X-chromosomes by a random inactivation process condenses to form X-chromatin (Barr body) in early embryonic life.", "The Barr body is the inactive X chromosome in a female somatic cell.", "There are three classical problems at the chromosome level in cytogenetics, namely the formation mechanisms and effects of Barr body, ", ". The fascination arose in part from the realisation that the inactive X corresponded to a dense heterochromatin mass called the \"Barr body\"", "The presence of a heavily stained condensed chromatin body (i.e., a Barr body) indicates the XX samples. ", "Interest has recently reawakened in whether loss of the heterochromatic X chromosome (Barr body) is prevalent in certain breast and ovarian cancers, and new insights into the mechanisms involved have emerged. ", "The colocalization of a 4,6-diamidino-2-phenylindole dihydrochloride-stained Barr body with one of the two painted X territories allowed the unequivocal discrimination of the inactive X from its active counterpart" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/21416650", "http://www.ncbi.nlm.nih.gov/pubmed/17611545", "http://www.ncbi.nlm.nih.gov/pubmed/23542155", "http://www.ncbi.nlm.nih.gov/pubmed/6270519", "http://www.ncbi.nlm.nih.gov/pubmed/21356720", "http://www.ncbi.nlm.nih.gov/pubmed/15682788", "http://www.ncbi.nlm.nih.gov/pubmed/12915472", "http://www.ncbi.nlm.nih.gov/pubmed/16980188", "http://www.ncbi.nlm.nih.gov/pubmed/8978813", "http://www.ncbi.nlm.nih.gov/pubmed/7973466", "http://www.ncbi.nlm.nih.gov/pubmed/10079142", "http://www.ncbi.nlm.nih.gov/pubmed/21811421", "http://www.ncbi.nlm.nih.gov/pubmed/22522168", "http://www.ncbi.nlm.nih.gov/pubmed/10393442" ]

[]

[ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0009048", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0001740", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:1900095", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:1900096", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:1900097", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012728" ]

[ "No, it is not yet feasible, although smaller pilot studies has been performed where a limited number of proteins has been analysed." ]

[ "no" ]

[ "Toward Single Cell Analysis by Plume Collimation in Laser Ablation Electrospray Ionization Mass Spectrometry.", "he advent of proteomics and genomics at a single-cell level has set the basis for an outstanding improvement in analytical technology and data acquisition.", "The new-generation technology of single-cell analysis is able to better characterize a cell's population, identifying and differentiating outlier cells, in order to provide both a single-cell experiment and a corresponding bulk measurement, through the identification, quantification and characterization of all system biology aspects (genomics, transcriptomics, proteomics, metabolomics, degradomics and fluxomics). The movement of omics into single-cell analysis represents a significant and outstanding shift.", "Laser ablation electrospray ionization (LAESI) is a novel method for the direct imaging of biological tissues by mass spectrometry. By performing ionization in the ambient environment, this technique enables in vivo studies with potential for single-cell analysis.", "Other approaches for MS-based chemical imaging and profiling include those based on near-field laser ablation and inductively-coupled plasma MS analysis, which offer complementary capabilities for subcellular chemical imaging and profiling.", "Mass spectrometry imaging and profiling of single cells.", "his is rapidly changing with the recent examples of single cell genomics, transcriptomics, proteomics and metabolomics. The rate of change is expected to accelerate owing to emerging technologies that range from micro/nanofluidics to microfabricated interfaces for mass spectrometry to third- and fourth-generation automated DNA sequencers", "Single-cell analysis (SCA) has been increasingly recognized as the key technology for the elucidation of cellular functions, which are not accessible from bulk measurements on the population level. Thus far, SCA has been achieved by miniaturization of established engineering concepts to match the dimensions of a single cell", "Single-cell proteomic chip for profiling intracellular signaling pathways in single tumor cells.", "The amount of single proteins in single cells can be as low as one copy per cell and is for most proteins in the attomole range or below; usually considered as insufficient for proteomic analysis.", "n Arabidopsis thaliana, we have successfully identified nine unique proteins in a single-cell sample and 56 proteins from a pool of 15 single-cell samples from glucosinolate-rich S-cells by nanoLC-MS/MS proteomic analysis, thus establishing the proof-of-concept for true single-cell proteomic analysis", "A first step towards practical single cell proteomics: a microfluidic antibody capture chip with TIRF detection." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/20680590", "http://www.ncbi.nlm.nih.gov/pubmed/16806894", "http://www.ncbi.nlm.nih.gov/pubmed/16098176", "http://www.ncbi.nlm.nih.gov/pubmed/22203961", "http://www.ncbi.nlm.nih.gov/pubmed/17560583", "http://www.ncbi.nlm.nih.gov/pubmed/18392595", "http://www.ncbi.nlm.nih.gov/pubmed/23445532", "http://www.ncbi.nlm.nih.gov/pubmed/20434785", "http://www.ncbi.nlm.nih.gov/pubmed/21708264", "http://www.ncbi.nlm.nih.gov/pubmed/22468600", "http://www.ncbi.nlm.nih.gov/pubmed/21347466", "http://www.ncbi.nlm.nih.gov/pubmed/15174138", "http://www.ncbi.nlm.nih.gov/pubmed/18664433", "http://www.ncbi.nlm.nih.gov/pubmed/17953400", "http://www.ncbi.nlm.nih.gov/pubmed/17439240", "http://www.ncbi.nlm.nih.gov/pubmed/18657818", "http://www.ncbi.nlm.nih.gov/pubmed/18682362", "http://www.ncbi.nlm.nih.gov/pubmed/22498881", "http://www.ncbi.nlm.nih.gov/pubmed/17109634", "http://www.ncbi.nlm.nih.gov/pubmed/22921068", "http://www.ncbi.nlm.nih.gov/pubmed/23256674" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D020543", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D059010", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0005623", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D002477", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D040901" ]

[ "Yes, shotgun lipidomics relies on direct infusion of total lipid extracts into a high-resolution tandem mass spectrometer." ]

[ "yes" ]

[ "In direct infusion/injection (or shotgun) lipidomics", "An efficient shotgun lipidomics strategy was established and optimized for fast phospholipid profiling of viscera from three fish species: Lateolabrax japonicas, Ctenopharyngodon idellus, and Carassius auratus. This strategy relies on direct infusion of total lipid extracts into a tandem mass spectrometer without additional separation of the individual molecular species. ", "Top-down shotgun lipidomics relies on direct infusion of total lipid extracts into a high-resolution tandem mass spectrometer", "shotgun lipidomic approaches that use direct infusion", "direct infusion (shotgun lipidomics) ", "direct infusion-based shotgun lipidomics approaches", "shotgun lipidomics (MDMS-SL) data, which are acquired directly from lipid extracts after direct infusion ", "Through direct infusion of the resultant enriched solution, we identified and quantitated a variety of very-low-abundance sphingolipid classes (e.g., sphingosine, psychosine, and lysosphingomyelin) and molecular species (e.g., sphingomyelin) using electrospray ionization mass spectrometry (i.e., shotgun sphingolipidomics)." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/17920553", "http://www.ncbi.nlm.nih.gov/pubmed/22629264", "http://www.ncbi.nlm.nih.gov/pubmed/19408941", "http://www.ncbi.nlm.nih.gov/pubmed/22946708", "http://www.ncbi.nlm.nih.gov/pubmed/21207296", "http://www.ncbi.nlm.nih.gov/pubmed/22282095", "http://www.ncbi.nlm.nih.gov/pubmed/23825371", "http://www.ncbi.nlm.nih.gov/pubmed/21755525" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D053719", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D008055", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013058", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013057", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D007260", "http://www.biosemantics.org/jochem#4269483" ]

[ "Mammaprint has a 70 gene signature." ]

[ "70 genes" ]

[ "The 70 gene-signature (MammaPrint(®)) is a prognostic profile of distant recurrence and survival of primary breast cancer (BC)", "The 70-gene signature was analysed using MammaPrint", "the prognostic value of the MammaPrint(TM) signature", "by the 70-gene signature", "the 70-gene signature", "n FDA-cleared 70-gene signature of MammaPrint panel", "70-gene MammaPrint signature", "70-gene signature", "The 70-gene signature (MammaPrint) is a prognostic test used to guide adjuvant treatment decisions in patients with node-negative breast cancer.", "70-gene signature.", "70-gene signature", "the 70-gene MammaPrint signature for chemotherapy (CT) benefit", "the 70-gene MammaPrint signature", "The 70-gene signature (MammaPrint) is a prognostic tool used to guide adjuvant treatment decisions.", "the 70-gene profile", "the 70-gene prognosis signature (MammaPrint) for node-negative breast cancer patients.", "70-gene signature.", "70-gene signature", "The MammaPrint 70-gene signature" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/22553468", "http://www.ncbi.nlm.nih.gov/pubmed/20094918", "http://www.ncbi.nlm.nih.gov/pubmed/23371464", "http://www.ncbi.nlm.nih.gov/pubmed/19126254", "http://www.ncbi.nlm.nih.gov/pubmed/20359886", "http://www.ncbi.nlm.nih.gov/pubmed/20204499", "http://www.ncbi.nlm.nih.gov/pubmed/21347257", "http://www.ncbi.nlm.nih.gov/pubmed/23347730", "http://www.ncbi.nlm.nih.gov/pubmed/21291290", "http://www.ncbi.nlm.nih.gov/pubmed/21081926", "http://www.ncbi.nlm.nih.gov/pubmed/22738860", "http://www.ncbi.nlm.nih.gov/pubmed/21479927", "http://www.ncbi.nlm.nih.gov/pubmed/21151591", "http://www.ncbi.nlm.nih.gov/pubmed/18483364", "http://www.ncbi.nlm.nih.gov/pubmed/18786252", "http://www.ncbi.nlm.nih.gov/pubmed/19214742" ]

[ { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A17680439", "o": "MammaPrint" } ]

[]

[ "Apixaban is a direct inhibitor of factor Xa, and is a potential alternative for the treatment of acute venous thromboembolism. These results suggest a lack of clear superiority of apixaban relative to enoxaparin. Apixaban is an oral alternative with similar efficacy and safety to existing anticoagulant therapies.", "Yes, apixaban is effective for treatment of acute venous thromboembolismis. Apixiban is a direct inhibitor of factor Xa, and is a potential alternative for the treatment of acute venous thromboembolism. Apixaban is an oral alternative with similar efficacy and safety to existing anticoagulant therapies." ]

[ "yes" ]

[ "Apixaban is a direct inhibitor of factor Xa, and is a potential alternative for the treatment of acute venous thromboembolism. ", "These results suggest a lack of clear superiority of apixaban relative to enoxaparin. Apixaban is an oral alternative with similar efficacy and safety to existing anticoagulant therapies.", "A fixed-dose regimen of apixaban alone was noninferior to conventional therapy for the treatment of acute venous thromboembolism and was associated with significantly less bleeding", "To critically review the effectiveness of the novel oral anticoagulants (rivaroxaban, dabigatran, ximelagatran, and apixaban) in the treatment of acute venous thromboembolism.", "ompared with vitamin K antagonists, the novel oral anticoagulants had a similar risk of recurrence of acute venous thromboembolism and all cause mortality, though rivaroxaban was associated with a reduced risk of bleeding", "Nowadays, the new anticoagulants, such as dabigatran, rivaroxaban and apixaban, show potential advantages over classical treatments. These agents inhibit specific coagulation factors and are administered orally at fixed doses.", "In a recently completed phase III trial, apixaban also demonstrated promising efficacy and safety in that indication", "the most advanced oral direct inhibitors to factor Xa (rivaroxaban and apixaban) and IIa (dabigatran)" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/18393142", "http://www.ncbi.nlm.nih.gov/pubmed/24554904", "http://www.ncbi.nlm.nih.gov/pubmed/23117646", "http://www.ncbi.nlm.nih.gov/pubmed/22153026", "http://www.ncbi.nlm.nih.gov/pubmed/24057162", "http://www.ncbi.nlm.nih.gov/pubmed/23808982", "http://www.ncbi.nlm.nih.gov/pubmed/22084658", "http://www.ncbi.nlm.nih.gov/pubmed/19014462", "http://www.ncbi.nlm.nih.gov/pubmed/22795419", "http://www.ncbi.nlm.nih.gov/pubmed/23233582", "http://www.ncbi.nlm.nih.gov/pubmed/19308891", "http://www.ncbi.nlm.nih.gov/pubmed/24278706", "http://www.ncbi.nlm.nih.gov/pubmed/23822763", "http://www.ncbi.nlm.nih.gov/pubmed/23150473" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013923", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013812", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D020246", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D054556", "http://www.biosemantics.org/jochem#4243936" ]

[ "Metabolic reprogramming is implicated in macrophage activation. In many cases, intermediates of the TCA cycle are involved in the response to hypoxic conditions brought about by inflammation." ]

[ "yes" ]

[ "In this study, the levels of amino acids and trichloroacetic acid (TCA) cycle-related molecules in the colonic tissues and sera of patients with ulcerative colitis (UC) were profiled by gas chromatography/mass spectrometry (GC/MS), with the aim of evaluating whether the clinical state induced by UC leads to variations in the amino acid profile", "Our study raises the possibility that GC/MS-based profiling of amino acids and TCA cycle-related molecules is a useful early diagnostic tool for UC.", "Succinate is an intermediate of the tricarboxylic acid (TCA) cycle, and plays a crucial role in adenosine triphosphate (ATP) generation in mitochondria.", "In plasma, most metabolites in the central metabolic pathway (glycolysis and TCA cycle) were significantly downregulated after zymosan administration", "Thus, IL-1beta+TNFalpha treated astrocytes show a marked decrease in glycogen levels, a slight but not significant decrease in lactate release as well as a massive increase in both the pentose phosphate pathway and TCA cycle activities.", "A total of 77 and 92 metabolites were detected in serum and colon tissue, respectively, and among the metabolites the compositions of TCA cycle intermediates and amino acids changed depending on the degree of colitis", "Extension of these findings identified a functional role for stretch-induced inhibition of succinate dehydrogenase (SDH) in mediating normoxic HIF1A stabilization, concomitant increases in glycolytic capacity, and improved tricarboxylic acid (TCA) cycle function", "These studies reveal a surprising role for HIF1A in lung protection during ALI, where normoxic HIF1A stabilization and HIF-dependent control of alveolar-epithelial glucose metabolism function as an endogenous feedback loop to dampen lung inflammation", "These results suggest a cataplerosis of the TCA cycle induced by phenobarbital, caused by the massive withdrawal of succinyl-CoA by ALAS induction, such that the TCA cycle is unable to supply the reduced cofactors to the RC", "The mitochondrial respiratory chain (RC) and the tricarboxylic acid (TCA) cycle were explored in the Hmbs(-/-) mouse model. RC and TCA cycle were significantly affected in comparison to controls in mice treated with phenobarbital with decreased activities of RC complexes", "Several changes in substrate utilization for energy homeostasis were identified in severe AAH, including increased glucose consumption by the pentose phosphate pathway, altered tricarboxylic acid (TCA) cycle activity, and enhanced peptide catabolism. ", "Enhanced mitochondrial glucose oxidation was achieved by increased recruitment of the NOTCH1 intracellular domain (NICD1) to nuclear and mitochondrial genes that encode respiratory chain components and by NOTCH-dependent induction of pyruvate dehydrogenase phosphatase 1 (Pdp1) expression, pyruvate dehydrogenase activity, and glucose flux to the TCA cycle. ", "Metabolic reprogramming is implicated in macrophage activation,", "BHB blocks the NLRP3 inflammasome without undergoing oxidation in the TCA cycle, and independently of uncoupling protein-2 (UCP2), sirtuin-2 (SIRT2), the G protein-coupled receptor GPR109A or hydrocaboxylic acid receptor 2 (HCAR2). ", "Our findings suggest that the anti-inflammatory effects of caloric restriction or ketogenic diets may be linked to BHB-mediated inhibition of the NLRP3 inflammasome.", "Succinate: a metabolic signal in inflammation." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/23776651", "http://www.ncbi.nlm.nih.gov/pubmed/24727425", "http://www.ncbi.nlm.nih.gov/pubmed/21523508", "http://www.ncbi.nlm.nih.gov/pubmed/24361092", "http://www.ncbi.nlm.nih.gov/pubmed/21287666", "http://www.ncbi.nlm.nih.gov/pubmed/25461442", "http://www.ncbi.nlm.nih.gov/pubmed/24086109", "http://www.ncbi.nlm.nih.gov/pubmed/25686106", "http://www.ncbi.nlm.nih.gov/pubmed/25798621", "http://www.ncbi.nlm.nih.gov/pubmed/18383346" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D007249", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D002952", "http://amigo.geneontology.org/amigo/term/GO:0006099" ]

[ "improving anemia control\nanemia management in hemodialysis\niron-restricted anemias" ]

[ "iron-restricted anemias", "anemia of inflammation", "anemia of cancer", "anemia of chronic kidney disease", "anemia of chronic disease" ]

[ "anti-hepcidin strategies for improving anemia control.", "anti-hepcidin therapies may improve anemia management in hemodialysis.", "Anti-hepcidin therapy for iron-restricted anemias", "human anti-hepcidin antibody as a novel therapeutic for iron-restricted anemias such as anemia of inflammation, cancer, or chronic kidney disease " ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/24159166", "http://www.ncbi.nlm.nih.gov/pubmed/24231125", "http://www.ncbi.nlm.nih.gov/pubmed/24175256" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D064451" ]

[ "The family Flaviviridae is comprised of three genera: Flavivirus, Pestivirus and Hepacivirus." ]

[ "three", "3" ]

[ "Within a project aimed at discovering new Flaviviridae inhibitors, new variously substituted 2-phenylbenzimidazoles were synthesized and evaluated in cell-based assays for cytotoxicity and antiviral activity against viruses representatives of the three genera of the Flaviviridae family, i.e.: Pestivirus (BVDV), Flavivirus (YFV) and Hepacivirus (HCV).", "Compounds were tested in cell-based assays against viruses representative of: i) two of the three genera of the Flaviviridae family, i.e. Pestiviruses and Flaviviruses;", "The RNA-stimulated NTPase activity of this protein from prototypic members of the Pestivirus and Flavivirus genera has recently been established and enzymologically characterized.", "Compounds were tested in cell-based assays against viruses representative of: i) two of the three genera of the Flaviviridae family, i.e. Flaviviruses and Pestiviruses; ii) other RNA virus families, such as Retroviridae, Picornaviridae, Paramyxoviridae, Rhabdoviridae and Reoviridae; iii) two DNA virus families (Herpesviridae and Poxviridae).", "Forty-three 2-[(benzotriazol-1/2-yl)methyl]benzimidazoles, bearing either linear (dialkylamino)alkyl- or bulkier (quinolizidin-1-yl)alkyl moieties at position 1, were evaluated in cell-based assays for cytotoxicity and antiviral activity against viruses representative of two of the three genera of the Flaviviridae family, i.e. Flaviviruses (Yellow Fever Virus (YFV)) and Pestiviruses (Bovine Viral Diarrhoea Virus (BVDV)), as Hepaciviruses can hardly be used in routine cell-based assays.", "Compounds were tested in cell-based assays against viruses representative of: i) two of the three genera of the Flaviviridae family, i.e. Flaviviruses and Pestiviruses; ii) other RNA virus families, such as Retroviridae, Picornaviridae, Paramyxoviridae, Rhabdoviridae and Reoviridae; iii) two DNA virus families (Herpesviridae and Poxviridae).", ": Pestivirus (BVDV), Flavivirus (YFV) and Hepacivirus (HCV).", "The family Flaviviridae contains three genera of positive-strand RNA viruses, namely, Flavivirus, Hepacivirus (e.g., hepatitis C virus [HCV]), and Pestivirus." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/21249176", "http://www.ncbi.nlm.nih.gov/pubmed/19555498", "http://www.ncbi.nlm.nih.gov/pubmed/19035566", "http://www.ncbi.nlm.nih.gov/pubmed/16225688", "http://www.ncbi.nlm.nih.gov/pubmed/8396675", "http://www.ncbi.nlm.nih.gov/pubmed/18991746", "http://www.ncbi.nlm.nih.gov/pubmed/22039536", "http://www.ncbi.nlm.nih.gov/pubmed/20470249", "http://www.ncbi.nlm.nih.gov/pubmed/19534676", "http://www.ncbi.nlm.nih.gov/pubmed/22513121", "http://www.ncbi.nlm.nih.gov/pubmed/22031952" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D018067" ]

[ "Yes, reduced-nicotine cigarettes are effective for smoking cessation." ]

[ "yes" ]

[ "CONCLUSIONS: In this 6-week study, reduced-nicotine cigarettes versus standard-nicotine cigarettes reduced nicotine exposure and dependence and the number of cigarettes smoked. ", "RESULTS: Significant reductions in nicotine intake were observed between usual brand smoking (∼1.2 mg nicotine) and the 0.3 and 0.05 mg nicotine emission cigarettes, but not the 0.6 mg cigarette.", "CONCLUSIONS: The study adds to the evidence that cigarettes with markedly reduced nicotine content are not associated with increased smoking intensity or exposure to smoke toxicants.", "BACKGROUND: When switching from usual brand cigarettes, very low nicotine content (VLNC) cigarettes lead to a reduction in the number of cigarettes smoked, toxicant exposure, withdrawal symptoms and dependence. ", "Moreover, while nicotine patches were well tolerated when subjects smoked nicotine-containing cigarettes, the use of nicotine skin patches with reduced-nicotine cigarettes potentially offers the advantage of increased efficacy without introducing concern about toxic effects of excessive nicotine intake.", "Results showed that Quest plus NRT was more effective than active control plus NRT in achieving 4 weeks of continuous abstinence (32.8% vs. 21.9%).", "Quest plus NRT offers promise as a new smoking cessation treatment.", "We identified three clinical trials (total n = 489) that suggest that smokers can dissociate nicotine delivery from the act of smoking if they use reduced-nicotine content cigarettes in combination with nicotine replacement therapy.", "CONCLUSION: The 0.05 mg nicotine yield cigarettes may be a tobacco product that can facilitate cessation; however, future research is clearly needed to support these preliminary findings.", "Preliminary studies suggest an extinction-based smoking cessation treatment using reduced nicotine content (RNC) cigarettes decreases self-report craving for cigarettes prior to quitting and may be an effective smoking cessation treatment.", "Reduced nicotine content (RNC) cigarettes have led to smoking fewer cigarettes, withdrawal relief, and facilitation of cessation.", "Evidence from a number of small smoking cessation studies suggests that the use of cigarettes with reduced nicotine content, in combination with nicotine replacement therapy (NRT), may help reduce withdrawal symptoms and increase quit rates.", "The concept for a reduced-nicotine cigarette designed to progressively wean smokers from the smoking habit is based on research demonstrating that successful smoking cessation is not only dependent on withdrawal of nicotine, but also on weaning from the habitual sensory and behavioral reinforcement of smoking.", "Preliminary studies suggest an extinction-based smoking cessation treatment using reduced nicotine content (RNC) cigarettes decreases self-report craving for cigarettes prior to quitting and may be an effective smoking cessation treatment", "Specifically, standards that required substantially reduced nicotine content in cigarettes could enable cessation in smokers and prevent future smoking among current non-smokers", "Reduced nicotine content (RNC) cigarettes have led to smoking fewer cigarettes, withdrawal relief, and facilitation of cessation", "Evidence from a number of small smoking cessation studies suggests that the use of cigarettes with reduced nicotine content, in combination with nicotine replacement therapy (NRT), may help reduce withdrawal symptoms and increase quit rates", "The concept for a reduced-nicotine cigarette designed to progressively wean smokers from the smoking habit is based on research demonstrating that successful smoking cessation is not only dependent on withdrawal of nicotine, but also on weaning from the habitual sensory and behavioral reinforcement of smoking", "These results suggest that use of NRT before a target quit-smoking date deserves further evaluation as a possible smoking cessation treatment. Moreover, while nicotine patches were well tolerated when subjects smoked nicotine-containing cigarettes, the use of nicotine skin patches with reduced-nicotine cigarettes potentially offers the advantage of increased efficacy without introducing concern about toxic effects of excessive nicotine intake.", "Preliminary studies suggest an extinction-based smoking cessation treatment using reduced nicotine content (RNC) cigarettes decreases self-report craving for cigarettes prior to quitting and may be an effective smoking cessation treatment." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/26422724", "http://www.ncbi.nlm.nih.gov/pubmed/25150282", "http://www.ncbi.nlm.nih.gov/pubmed/21232155", "http://www.ncbi.nlm.nih.gov/pubmed/25025523", "http://www.ncbi.nlm.nih.gov/pubmed/24746485", "http://www.ncbi.nlm.nih.gov/pubmed/17573781", "http://www.ncbi.nlm.nih.gov/pubmed/23603206", "http://www.ncbi.nlm.nih.gov/pubmed/16497603", "http://www.ncbi.nlm.nih.gov/pubmed/18629723", "http://www.ncbi.nlm.nih.gov/pubmed/19793786", "http://www.ncbi.nlm.nih.gov/pubmed/20078491" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016540" ]

[ "Yes, \tNotum deacylates Wnt proteins to suppress signalling activity." ]

[ "yes" ]

[ "Notum deacylates Wnt proteins to suppress signalling activity.", "Kinetic and mass spectrometric analyses of human proteins show that Notum is a carboxylesterase that removes an essential palmitoleate moiety from Wnt proteins and thus constitutes the first known extracellular protein deacylase.", "the Wnt inhibitor notum", "the WNT-inhibitor notum." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/18505598", "http://www.ncbi.nlm.nih.gov/pubmed/22669824", "http://www.ncbi.nlm.nih.gov/pubmed/22159580", "http://www.ncbi.nlm.nih.gov/pubmed/18429952", "http://www.ncbi.nlm.nih.gov/pubmed/24523458", "http://www.ncbi.nlm.nih.gov/pubmed/15647319", "http://www.ncbi.nlm.nih.gov/pubmed/25731175", "http://www.ncbi.nlm.nih.gov/pubmed/10049571", "http://www.ncbi.nlm.nih.gov/pubmed/24992682" ]

[]

[]

[ "The FOUR (Full Outline of UnResponsiveness) score, a new coma scale, evaluates 4 components: eye and motor responses, brainstem reflexes and respiration." ]

[ "eye responses", "motor responses", "brainstem reflexes", "respiration" ]

[ "The Full Outline of UnResponsiveness (FOUR) Score is a coma scale that consists of four components (eye and motor response, brainstem reflexes, and respiration). ", "Recently, the full outline of unresponsiveness (FOUR) score was introduced, which is composed of four clinically distinct categories of evaluation: eye reaction, motor function, brainstem reflexes and respiratory pattern. ", "The FOUR (Full Outline of UnResponsiveness) score, a new coma scale, evaluates 4 components: eye and motor responses, brainstem reflexes and respiration. ", "The FOUR (Full Outline of UnResponsiveness) score, a new coma scale, evaluates 4 components: eye and motor responses, brainstem reflexes and respiration.", "To evaluate the validity of the FOUR (Full Outline of UnResponsiveness) score (ranging from 0 to 16), a new coma scale consisting of 4 components (eye response, motor response, brainstem reflexes, and respiration pattern), when used by the staff members of a medical intensive care unit (ICU).", "To evaluate the validity of the FOUR (Full Outline of UnResponsiveness) score (ranging from 0 to 16), a new coma scale consisting of 4 components (eye response, motor response, brainstem reflexes, and respiration pattern), when used by the staff members of a medical intensive care unit (ICU).", "Recently, the full outline of unresponsiveness (FOUR) score was introduced, which is composed of four clinically distinct categories of evaluation: eye reaction, motor function, brainstem reflexes and respiratory pattern.", "The FOUR (Full Outline of UnResponsiveness) score, a new coma scale, evaluates 4 components: eye and motor responses, brainstem reflexes and respiration." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/24556655", "http://www.ncbi.nlm.nih.gov/pubmed/19648386", "http://www.ncbi.nlm.nih.gov/pubmed/24013867", "http://www.ncbi.nlm.nih.gov/pubmed/20551672" ]

[]

[]

[ "Nose, ear and meniscus prototypes/constructs have been produced with 3D (3-dimesional) printing." ]

[ "nose", "ear", "meniscus" ]

[ "To determine the potential of an integrated, image-based computer-aided design (CAD) and 3-dimensional (3D) printing approach to engineer scaffolds for head and neck cartilaginous reconstruction for auricular and nasal reconstruction.", "Subcutaneous in vivo implantation of auricular and nasal scaffolds was performed in a porcine model.", "Auricular and nasal constructs with several types of microporous architecture were rapidly manufactured with high fidelity to human patient anatomy. Subcutaneous in vivo implantation of auricular and nasal scaffolds resulted in an excellent appearance and complete soft tissue ingrowth. Histological analysis of in vitro scaffolds demonstrated native-appearing cartilaginous growth that respected the boundaries of the scaffold.CONCLUSION: Integrated, image-based CAD and 3D printing processes generated patient-specific nasal and auricular scaffolds that supported cartilage regeneration.", "A prototype meniscus cartilage was prepared to illustrate the potential application in bioengineering.", "As a proof of concept, we generated a bionic ear via 3D printing of a cell-seeded hydrogel matrix in the anatomic geometry of a human ear, along with an intertwined conducting polymer consisting of infused silver nanoparticles. This allowed for in vitro culturing of cartilage tissue around an inductive coil antenna in the ear, which subsequently enables readout of inductively-coupled signals from cochlea-shaped electrodes. The printed ear exhibits enhanced auditory sensing for radio frequency reception, and complementary left and right ears can listen to stereo audio music. ", "In this study, we describe the construction of a hybrid inkjet printing/electrospinning system that can be used to fabricate viable tissues for cartilage tissue engineering applications.", "Before 3D Printing can be used routinely for the regeneration of complex tissues (e.g. bone, cartilage, muscles, vessels, nerves in the craniomaxillofacial complex), and complex organs with intricate 3D microarchitecture (e.g. liver, lymphoid organs), several technological limitations must be addressed", "3D Printing promises to produce complex biomedical devices according to computer design using patient-specific anatomical data", "3D printing of HEK 293FT cell-laden hydrogel into macroporous constructs with high cell viability and normal biological functions.", "3D-printing of lightweight cellular composites.", "3D bioprinting is being applied to regenerative medicine to address the need for tissues and organs suitable for transplantation. ", "In this paper, we reported a novel study of 3D printing of cell lines derived from human embryonic kidney tissue into a macroporous tissue-like construct. ", "Compared with non-biological printing, 3D bioprinting involves additional complexities, such as the choice of materials, cell types, growth and differentiation factors, and technical challenges related to the sensitivities of living cells and the construction of tissues. ", "Organ printing, which we define as computer-aided, jet-based 3D tissue-engineering of living human organs, offers a possible solution. Organ printing involves three sequential steps: pre-processing or development of \"blueprints\" for organs; processing or actual organ printing; and postprocessing or organ conditioning and accelerated organ maturation.", "Organ printing involves three sequential steps: pre-processing or development of \"blueprints\" for organs; processing or actual organ printing; and postprocessing or organ conditioning and accelerated organ maturation.", "Bioprinting has no or little side effect to the printed mammalian cells and it can conveniently combine with gene transfection or drug delivery to the ejected living systems during the precise placement for tissue construction.", "Compared with non-biological printing, 3D bioprinting involves additional complexities, such as the choice of materials, cell types, growth and differentiation factors, and technical challenges related to the sensitivities of living cells and the construction of tissues.", "Innovations in 3D printing: a 3D overview from optics to organs.", "Organ printing: computer-aided jet-based 3D tissue engineering." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/22436025", "http://www.ncbi.nlm.nih.gov/pubmed/19901446", "http://www.ncbi.nlm.nih.gov/pubmed/25197745", "http://www.ncbi.nlm.nih.gov/pubmed/25387454", "http://www.ncbi.nlm.nih.gov/pubmed/25641220", "http://www.ncbi.nlm.nih.gov/pubmed/24288392", "http://www.ncbi.nlm.nih.gov/pubmed/23822094", "http://www.ncbi.nlm.nih.gov/pubmed/25839977", "http://www.ncbi.nlm.nih.gov/pubmed/25093879", "http://www.ncbi.nlm.nih.gov/pubmed/12740943", "http://www.ncbi.nlm.nih.gov/pubmed/24805923", "http://www.ncbi.nlm.nih.gov/pubmed/25281749", "http://www.ncbi.nlm.nih.gov/pubmed/23635097", "http://www.ncbi.nlm.nih.gov/pubmed/24942232", "http://www.ncbi.nlm.nih.gov/pubmed/25492194", "http://www.ncbi.nlm.nih.gov/pubmed/25159591", "http://www.ncbi.nlm.nih.gov/pubmed/23172542", "http://www.ncbi.nlm.nih.gov/pubmed/2087655", "http://www.ncbi.nlm.nih.gov/pubmed/25866560", "http://www.ncbi.nlm.nih.gov/pubmed/18154465", "http://www.ncbi.nlm.nih.gov/pubmed/25691496" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D066330", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011327" ]

[ "Yes, ospamifene is effective for treatment of dyspareunia. Ospemifene is a selective estrogen receptor modulator, or estrogen receptor agonist/antagonist, that was recently approved by the US Food and Drug Administration for the treatment of dyspareunia associated with vulvar and vaginal atrophy, a chronic condition that affects up to 60% of postmenopausal women. Ospemifene is the first non-estrogen treatment approved for moderate to severe dyspareunia in women with menopause-related vulvar and vaginal atrophy." ]

[ "yes" ]

[ "Ospemifene, a novel selective estrogen receptor modulator, has been developed for the treatment of vulvovaginal atrophy and dyspareunia in postmenopausal women. ", "For the comparison of short-term ospemifene with placebo, parabasal cells (the standardized mean difference [SMD] = -37.5, 95% confidence interval [CI] = -41.83 to -33.17, P < 0.00001), superficial cells (SMD = 9.24, 95% CI = 7.70 to 10.79, P < 0.00001), vaginal PH (SMD = -0.89, 95% CI = -0.98 to -0.80, P = 0.00001), and dyspareunia (SMD = -0.37, 95% CI = -0.43 to -0.30, P = 0.00001) indicated that ospemifene was more effective than the placebo. ", "This meta-analysis indicates that ospemifene to be an effective and safe treatment for dyspareunia associated with postmenopausal vulvar and vaginal atrophy.", "Ospemifene is a selective estrogen receptor modulator (SERM), or estrogen receptor agonist/antagonist, that was recently approved by the US Food and Drug Administration for the treatment of dyspareunia associated with vulvar and vaginal atrophy, a chronic condition that affects up to 60% of postmenopausal women.", "In conclusion, ospemifene is a SERM with a unique estrogen agonist/antagonist tissue profile that was recently approved in the US for the treatment of dyspareunia associated with vulvar and vaginal atrophy in postmenopausal women. ", "To characterize the pharmacokinetics of the oral, non-estrogen agent ospemifene, an estrogen agonist/antagonist with tissue-selective effects (also called a selective estrogen receptor modulator) that was recently approved for the treatment of dyspareunia associated with vulvar and vaginal atrophy in postmenopausal women.", "Here, we review the estrogen agonist/antagonist profile of ospemifene, a novel triphenylethylene derivative recently approved to treat dyspareunia, a symptom of vulvar and vaginal atrophy (VVA) due to menopause, both preclinically and clinically.", " Long-term studies on the endometrial safety of local estrogen and ospemifene are lacking. ", "Ospemifene is a tissue-selective estrogen agonist/antagonist (a selective estrogen receptor modulator) recently approved by the US Food and Drug Administration for treatment of dyspareunia, a symptom of VVA, due to menopause.", "SERMs with positive vaginal effects (such as improvement in the vaginal maturation index, reduced vaginal pH, and improvement in the signs and symptoms of VVA) on postmenopausal symptomatic women include lasofoxifene (clinical development on hold) and ospemifene, which was recently approved for the treatment of VVA-related dyspareunia, with a class effect warning of potential venous thrombosis risk. ", "Ospemifene is the first non-estrogen treatment approved for moderate to severe dyspareunia in women with menopause-related vulvar and vaginal atrophy. ", "This article summarizes the milestones in the development of ospemifene leading to this first approval for moderate to severe dyspareunia, a symptom of postmenopausal vulvar and vaginal atrophy.", "The aim of this work was to study the role of ospemifene, a novel selective estrogen receptor modulator, in the treatment of vulvar and vaginal atrophy in postmenopausal women with moderate to severe dyspareunia and physiological vaginal changes. ", "In this study, once-daily oral ospemifene 60 mg was effective for the treatment of vulvar and vaginal atrophy in postmenopausal women with dyspareunia.", "Clinical trials have confirmed that daily doses are well-tolerated and that it is effective in normalizing vaginal maturation index and pH as well as improving the symptoms associated with VVA including dyspareunia.", "Ospemifene was shown to be effective and well tolerated for the treatment of the symptoms of vaginal dryness and dyspareunia associated with vulvovaginal atrophy over and above the use of provided lubricants." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/24055829", "http://www.ncbi.nlm.nih.gov/pubmed/24075094", "http://www.ncbi.nlm.nih.gov/pubmed/23985562", "http://www.ncbi.nlm.nih.gov/pubmed/23605694", "http://www.ncbi.nlm.nih.gov/pubmed/23945733", "http://www.ncbi.nlm.nih.gov/pubmed/24109197", "http://www.ncbi.nlm.nih.gov/pubmed/20032798", "http://www.ncbi.nlm.nih.gov/pubmed/20429673", "http://www.ncbi.nlm.nih.gov/pubmed/23361170", "http://www.ncbi.nlm.nih.gov/pubmed/23777900", "http://www.ncbi.nlm.nih.gov/pubmed/24251418" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013812", "http://www.biosemantics.org/jochem#4226329", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004414" ]

[ "Yes, numerous evidence from clinical trials indicate that pregabalic is effective for treatment of patients diagnosed with restless leg syndrome." ]

[ "yes" ]

[ "CONCLUSIONS: This study demonstrated improvements in objective and subjective measures of sleep maintenance and sleep architecture with pregabalin compared with placebo and pramipexole. Effects of pregabalin on periodic limb movement arousal index were comparable to pramipexole. ", "CONCLUSIONS: Pregabalin provided significantly improved treatment outcomes as compared with placebo, and augmentation rates were significantly lower with pregabalin than with 0.5 mg of pramipexole.", "The alpha-2-delta ligands, including gabapentin, gabapentin enacarbil, and pregabalin, are effective for RLS without known occurrence of augmentation or impulse control disorders, although sedation and dizziness can occur. ", "Pregabalin has been established as effective for up to 1 year in treating RLS/WED (Level A evidence). ", "In the group of anticonvulsants, only the trials performed with α₂δ ligands such as gabapentin, gabapentin enacarbil, and pregabalin showed good efficacy. ", "Alternative or additional pharmacologic treatment with a lower level of overall quality of evidence includes opioids (codeine, tramadol, and oxycodone) and anticonvulsants (gabapentin, gabapentin enacarbil, and pregabalin). ", "There is sufficient evidence to conclude that dopamine agonists such as rotigotine transdermal patch, pramipexole, ropinirole, gabapentin enacarbil, pregabalin and gabapentin are effective in the short-term treatment of RLS and rotigotine, followed by gabapentin enacarbil, ropinirole, pramipexole and gabapentin for long-term treatment.", "Calcium channel alpha-2-delta ligands (gabapentin, gabapentin enacarbil, and pregabalin) provide alternative therapies for RLS especially in patients with augmentation, impulse control disorders, or hypersomnia induced by dopamine agonists. ", "Alpha-2-delta ligands (gabapentin enacarbil, gabapentin, and pregabalin) increased the number of IRLS responders (RR=1.66; [95% CI: 1.33 to 2.09], k=3, high strength of evidence) and mean change in IRLS symptom scores (k=3, high strength of evidence). ", "RECOMMENDATIONS: Level A recommendations can be made for rotigotine, ropinirole, pramipexole, gabapentin enacarbil, gabapentin and pregabalin, which are all considered effective for the short-term treatment for RLS.", "Therapies with an OPTION level of recommendation include carbamazepine, gabapentin, pregabalin, clonidine, and for patients with low ferritin levels, iron supplementation.", "CONCLUSIONS: In this 6-week phase 2b study, pregabalin reduced RLS symptoms in patients with moderate-to-severe idiopathic RLS", "CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that pregabalin is effective for the treatment of restless legs syndrome and improves sleep architecture and periodic limb movements in placebo-unresponsive patients.", "In severe, refractory or neuropathy-associated RLS, antiepileptic (gabapentin, pregabalin) or opioid (oxycodone, tramadol) drugs can be used.", "The alpha-2-delta ligands, including gabapentin, gabapentin enacarbil, and pregabalin, are effective for RLS without known occurrence of augmentation or impulse control disorders, although sedation and dizziness can occur", "This study provides Class II evidence that pregabalin is effective for the treatment of restless legs syndrome and improves sleep architecture and periodic limb movements in placebo-unresponsive patients.", "Level A recommendations can be made for rotigotine, ropinirole, pramipexole, gabapentin enacarbil, gabapentin and pregabalin, which are all considered effective for the short-term treatment for RLS" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/23859128", "http://www.ncbi.nlm.nih.gov/pubmed/22851801", "http://www.ncbi.nlm.nih.gov/pubmed/18656214", "http://www.ncbi.nlm.nih.gov/pubmed/24521108", "http://www.ncbi.nlm.nih.gov/pubmed/17489946", "http://www.ncbi.nlm.nih.gov/pubmed/23746768", "http://www.ncbi.nlm.nih.gov/pubmed/24363103", "http://www.ncbi.nlm.nih.gov/pubmed/23385700", "http://www.ncbi.nlm.nih.gov/pubmed/22937989", "http://www.ncbi.nlm.nih.gov/pubmed/24119681", "http://www.ncbi.nlm.nih.gov/pubmed/20466589", "http://www.ncbi.nlm.nih.gov/pubmed/24899755", "http://www.ncbi.nlm.nih.gov/pubmed/23524988", "http://www.ncbi.nlm.nih.gov/pubmed/22570552", "http://www.ncbi.nlm.nih.gov/pubmed/20427750", "http://www.ncbi.nlm.nih.gov/pubmed/23771546", "http://www.ncbi.nlm.nih.gov/pubmed/23703310", "http://www.ncbi.nlm.nih.gov/pubmed/23304742" ]

[]

[ "http://www.biosemantics.org/jochem#4236113" ]

[ "Expansins are extracellular proteins that increase plant cell-wall extensibility. These wall-loosening proteins are involved in cell wall extension and polysaccharide degradation. In fungi expansins and expansin-like proteins have been found to localize in the conidial cell wall and are probably involved in cell wall remodeling during germination." ]

[]

[ "interactions with alpha-expansin in cell wall extension and polysaccharide degradation", "cell wall swelling may not be a significant event during the action of expansin and hydrolases", "To evaluate a putative implication of three newly identified expansin/family 45 endoglucanase-like (EEL) proteins in lignocellulose degradation", "Our results show that EglD is a conidial cell wall localized expansin-like protein, which could be involved in cell wall remodeling during germination", "Swollenin, a protein first characterized in the saprophytic fungus Trichoderma reesei, contains an N-terminal carbohydrate-binding module family 1 domain (CBD) with cellulose-binding function and a C-terminal expansin-like domain", "alpha-Expansins are extracellular proteins that increase plant cell-wall extensibility", "these wall-loosening proteins are directly involved in the accommodation of the fungus by infected cortical cells" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/15195944", "http://www.ncbi.nlm.nih.gov/pubmed/18400936", "http://www.ncbi.nlm.nih.gov/pubmed/20478643", "http://www.ncbi.nlm.nih.gov/pubmed/18406638", "http://www.ncbi.nlm.nih.gov/pubmed/15605243", "http://www.ncbi.nlm.nih.gov/pubmed/19479322" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005658" ]

[ "Yes, zinc finger nucleases are a useful tool for treating disease." ]

[ "yes" ]

[ "Genetic engineering has emerged as a powerful mechanism for understanding biological systems and a potential approach for redressing congenital disease.", "This is of particular importance, given the momentum currently behind ZFNs in moving into phase I clinical trials. This study provides a historical account of the origins of ZFN technology, an analysis of current techniques and applications, and an examination of the ethical issues applicable to translational ZFN genetic engineering in early phase clinical trials.", "This broad range of tractable species renders ZFNs a useful tool for improving the understanding of complex physiological systems, to produce transgenic animals, cell lines, and plants, and to treat human disease.", "We observe comparably high frequencies in human T cells, raising the possibility of strategies based on zinc-finger nucleases for the treatment of disease.", "Using engineered nucleases, such as Zinc Finger Nucleases (ZFNs) or Transcription Activator-Like Effector Nucleases (TALENs), to make targeted genomic modifications has become a common technique to create new model organisms and custom cell lines, and has shown great promise for disease treatment.", "Zinc Finger nucleases (ZFNs) have been used to create precise genome modifications at frequencies that might be therapeutically useful in gene therapy.", "Zinc finger nucleases as tools to understand and treat human diseases.", "Evaluation of novel design strategies for developing zinc finger nucleases tools for treating human diseases.", "An over expression APP model for anti-Alzheimer disease drug screening created by zinc finger nuclease technology.", "Oxidase-deficient neutrophils from X-linked chronic granulomatous disease iPS cells: functional correction by zinc finger nuclease-mediated safe harbor targeting.", "Recently, it has been shown that targeted mutagenesis using zinc-finger nucleases (ZFNs) and transcription activator-like effector nucleases (TALENs) can be used to generate knockout zebrafish lines for analysis of their function and/or developing disease models", "Using engineered nucleases, such as Zinc Finger Nucleases (ZFNs) or Transcription Activator-Like Effector Nucleases (TALENs), to make targeted genomic modifications has become a common technique to create new model organisms and custom cell lines, and has shown great promise for disease treatment", "Gene correction by homologous recombination with zinc finger nucleases in primary cells from a mouse model of a generic recessive genetic disease.", "raising the possibility of strategies based on zinc-finger nucleases for the treatment of disease." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/15806097", "http://www.ncbi.nlm.nih.gov/pubmed/16082368", "http://www.ncbi.nlm.nih.gov/pubmed/22318089", "http://www.ncbi.nlm.nih.gov/pubmed/20389291", "http://www.ncbi.nlm.nih.gov/pubmed/18511461", "http://www.ncbi.nlm.nih.gov/pubmed/23161061", "http://www.ncbi.nlm.nih.gov/pubmed/21631241", "http://www.ncbi.nlm.nih.gov/pubmed/20846404", "http://www.ncbi.nlm.nih.gov/pubmed/20594338", "http://www.ncbi.nlm.nih.gov/pubmed/24557916", "http://www.ncbi.nlm.nih.gov/pubmed/24808958" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016335", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D015032", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004194", "http://www.disease-ontology.org/api/metadata/DOID:4" ]

[ "From 10.2% to 38% acoustic neuroma patients report depression. Depression is predicted by the number of symptoms, prolonged postoperative headache, deterioration of hearing and female gender." ]

[]

[ "Clinically significant anxiety was reported by 29.8% of participants and 10.2% were depressed. ", "Time since management, number of symptoms and comorbid medical conditions predicted anxiety, while depression was predicted by number of symptoms. ", "Depression (usually mild) occurred in 24% of the respondents, being significantly more common in prolonged postoperative headache patients. ", "Three patients had a depressive disorder in the preoperative assessment. Of the remaining 24 patients, nine (38%) had a depressive disorder at the three month check up. Deterioration of hearing was the only postoperative detriment associated with a depressive disorder (P = 0·024). All nine patients with a depressive disorder were women (P = 0·001), giving them a 69% incidence.", "Content analysis indicated that the majority of subjects experienced tiredness, depression, headache, and dryness of eyes and mouth in the postoperative and convalescent phases. ", "Treating physicians should be aware that as the number of acoustic neuroma symptoms increases, so may the likelihood of clinically significant anxiety and depression.", "Treating physicians should be aware that as the number of acoustic neuroma symptoms increases, so may the likelihood of clinically significant anxiety and depression.", "Clinically significant anxiety was reported by 29.8% of participants and 10.2% were depressed.", "Time since management, number of symptoms and comorbid medical conditions predicted anxiety, while depression was predicted by number of symptoms.", "This appears to be the first study among acoustic neuroma patients in which anxiety and depression were compared across management options. Treating physicians should be aware that as the number of acoustic neuroma symptoms increases, so may the likelihood of clinically significant anxiety and depression.", "Time since management, number of symptoms and comorbid medical conditions predicted anxiety, while depression was predicted by number of symptoms. This appears to be the first study among acoustic neuroma patients in which anxiety and depression were compared across management options." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/17711494", "http://www.ncbi.nlm.nih.gov/pubmed/8965089", "http://www.ncbi.nlm.nih.gov/pubmed/22051029", "http://www.ncbi.nlm.nih.gov/pubmed/2775668" ]

[]

[ "http://www.disease-ontology.org/api/metadata/DOID:12689", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D003863", "http://www.disease-ontology.org/api/metadata/DOID:1596", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009464" ]

[ "Achondroplasia is due to mutations in the fibroblast growth factor receptor 3 (FGFR3) gene." ]

[ "fibroblast growth factor receptor 3 (FGFR3)" ]

[ "She was subsequently diagnosed with hypochondroplasia at the age of 6 years when disproportional short stature, stocky habitus and macrocephaly were observed. These phenotypic findings were later confirmed by the presence of fibroblast growth factor receptor 3 (FGFR3) gene mutation N540K.", "Achondroplasia can be diagnosed by characteristic clinical and radiographic findings in most affected individuals. In individuals who may be too young to diagnose with certainty or in individuals with atypical findings, molecular genetic testing can be used to detect a mutation in FGFR3.", "Achondroplasia comes from the genetic point mutations in the fibroblastic growth factor receptor 3 gene (FGFR3), which enables abnormal cartilage growth-plate differentiation and insufficient bony development. The most common genetic mutations in this receptor are G to A at position 1138 (G1138A), which result in the substitution of glycine to arginine at codon 380.", "To investigate the mutation at the transmembrane domain of fibroblast growth factor receptor 3 (FGFR3) nucleotide 1138 site for identifying the major pathologic mechanism of achondroplasia (ACH) and to evaluate the efficacy of denaturing gradient gel electrophoresis(DGGE) method for screening the point mutations. ", "Nucleotide 1138 in transmembrane domain of FGFR3 gene is the hot point for mutation in ACH and hence its major pathologic cause. ", "The nucleotide 1138 of FGFR3 gene is also the hotspot of mutation in Chinese patients with ACH. A simple and rapid molecular diagnostic method has been set up to differentiate ACH from other similar genetic dwarfism.", "The diagnosis of achondroplasia was based on the presence of clinical and radiographic findings and confirmed by the presence of a common FGFR3 gene mutation (Gly380Arg) detected by restriction enzyme analysis and sequencing of the polymerase chain reaction products.", "All patients carried the same glycine-to-arginine mutation at codon 380(G380R) of the transmembrane domain of FGFR3. ", "The results suggest that the G380R mutation of FGFR3 is also a frequent mutation causing achondroplasia in Chinese. Detecting FGFR 3 gene mutation with PCR-SSCP and restriction enzymes analysis is a convenient, rapid and reliable molecular diagnostic assay for prenatal and early diagnosis of achondroplasia.", "To evaluate whether mutation in the exon 10 of the fibroblast growth factor receptor 3(FGFR3) gene in common in Chinese patients with achondroplasia.", "Achondroplasia (ACH) is the most frequent form of short-limb dwarfism. Recently, the gene mutation responsible for ACH has been identified in the transmembrane domain of the fibroblast growth factor receptor 3 gene. The cause of ACH is a point mutation at nucleotide 1138 of the cDNA, resulting in the substitution of an arginine residue for a glycine. ", "Recent studies mapped the achondroplasia gene on chromosome region 4p16.3 and identified a common mutation in the gene encoding the fibroblast growth factor receptor 3 (FGFR3). " ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/10932008", "http://www.ncbi.nlm.nih.gov/pubmed/10881785", "http://www.ncbi.nlm.nih.gov/pubmed/9115628", "http://www.ncbi.nlm.nih.gov/pubmed/7702086", "http://www.ncbi.nlm.nih.gov/pubmed/9949234", "http://www.ncbi.nlm.nih.gov/pubmed/15221641", "http://www.ncbi.nlm.nih.gov/pubmed/20301331", "http://www.ncbi.nlm.nih.gov/pubmed/12048679" ]

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[ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D000130", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009154", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005796" ]

[ "Pharmacologic inhibition of Hsp90 involves interaction with the ATP-binding site of the chaperone. This exerts antiproliferative effects resulting in a marked suppression of tumor growth. Following treatment with a Hsp90 inhibitor, expression of a number of proteins is affected, and most notably the Hsp90 clients, leading to dysregulation of intracellular signal transduction, immune response, cell growth and maintenance, transport, and metabolism, finally resulting in cancer cell death through activation of both intrinsic and extrinsic apoptotic pathways." ]

[]

[ "In vitro, we show that pharmacologic inhibition of Hsp90 by IPI-504 exerts antiproliferative effects in a panel of pancreatic cancer cells in a dose- and time-dependent manner.", "In pancreatic cancer xenografts obtained directly from patients with pancreas cancer, the agent resulted in a marked suppression of tumor growth.", "Using a proteomic profiling analysis with isotope tags for relative and absolute quantitation labeling technique, we have identified 20 down-regulated proteins and 42 up-regulated proteins on IPI-504 treatment.tumor growth Identical changes were observed in the expression of the genes coding for these proteins in a subset of proteins including HSPA1B, LGALS3, CALM1, FAM84B, FDPS, GOLPH2, HBA1, HIST1H1C, HLA-B, and MARCKS. The majority of these proteins belong to the functional class of intracellular signal transduction, immune response, cell growth and maintenance, transport, and metabolism.", "Dicoumarol, a long-established oral anticoagulant, is a new Hsp90 inhibitor that represses PTTG1/Securin gene expression and provokes apoptosis through a complex trait involving both intrinsic and extrinsic pathways.", "Dicoumarol activity as an Hsp90 inhibitor is confirmed by smaller levels of Hsp90 clients in treated cells and inhibition of in vivo heat shock luciferase activity recovery assays.", "Likewise, established Hsp90 inhibitors (17-allylamino-geldanamycin and novobiocin) repress PTTG1/Securin gene expression. ", "However, effects on PTTG1/Securin could be partially ascribed to inhibition of the Ras/Raf/extracellular signal-regulated kinase pathway.", "To document this field, we have studied two Hsp90 inhibitors (radicicol and geldanamycin), known to interact with the ATP-binding site of Hsp90 (the Bergerat fold),", "One of these is the novel agent 17-allylamino-17-demethoxygeldanamycin that acts to inhibit the hsp90 molecular chaperone. Treatment of four human colon cancer cell lines with iso-effective concentrations of this agent resulted in depletion of c-raf-1 and akt and inhibition of signal transduction.", "The expression of hsp90 client protein genes was not affected, but hsc hsp70, hsp90beta, keratin 8, keratin 18 and caveolin-1 were deregulated following treatment." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/18852131", "http://www.ncbi.nlm.nih.gov/pubmed/18347135", "http://www.ncbi.nlm.nih.gov/pubmed/15849317", "http://www.ncbi.nlm.nih.gov/pubmed/10962573" ]

[]

[ "http://www.uniprot.org/uniprot/HSP82_ENCCU", "http://www.uniprot.org/uniprot/HSP90_THEPA", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0051879", "http://www.uniprot.org/uniprot/HSP90_ASPFU", "http://www.biosemantics.org/jochem#4175054", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D018841", "http://www.uniprot.org/uniprot/HSP90_BRUPA", "http://www.uniprot.org/uniprot/HSP90_EIMTE", "http://www.uniprot.org/uniprot/HSP90_THEAN", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D045504", "http://www.uniprot.org/uniprot/H90A1_DANRE", "http://www.biosemantics.org/jochem#4250710", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D020228" ]

[ "The RET proto-oncogene is the major gene associated to Hirschsprung disease (HSCR) with differential contributions of its rare and common, coding and noncoding mutations to the multifactorial nature of this pathology.", "RET is the major gene associated to Hirschsprung disease (HSCR) with differential contributions of its rare and common, coding and noncoding mutations to the multifactorial nature of this pathology " ]

[ "yes" ]

[ "The RET proto-oncogene is the major gene associated to HSCR with differential contributions of its rare and common, coding and noncoding mutations to the multifactorial nature of this pathology", "The RET proto-oncogene is the major gene for HSCR with differential contributions of its rare and common, coding and noncoding mutations to the multifactorial nature of this pathology", "The rearranged during transfection gene (RET) is considered the major gene in HSCR", "RET is the major gene associated to Hirschsprung disease (HSCR) with differential contributions of its rare and common, coding and noncoding mutations to the multifactorial nature of this pathology", "While all Mendelian modes of inheritance have been described in syndromic HSCR, isolated HSCR stands as a model for genetic disorders with complex patterns of inheritance. The tyrosine kinase receptor RET is the major gene with both rare coding sequence mutations and/or a frequent variant located in an enhancer element predisposing to the disease", " The rearranged during transfection (RET) proto-oncogene is the major susceptibility gene for Hirschsprung disease, and germline mutations in RET have been reported in up to 50% of the inherited forms of Hirschsprung disease and in 15-20% of sporadic cases of Hirschsprung disease.", "The RET proto-oncogene is the major gene involved in the complex genetics of Hirschsprung disease (HSCR), or aganglionic megacolon, showing causative loss-of-function mutations in 15-30% of the sporadic cases.", "The major gene for Hirschsprung disease (HSCR) encodes the receptor tyrosine kinase RET.", "The RET proto-oncogene is considered to be the major susceptibility gene involved in Hirschsprung disease.", " Hirschsprung disease (HSCR), a developmental disorder characterized by the absence of enteric neurons in distal segments of the gut, shows a complex pattern of inheritance, with the RET protooncogene acting as a major gene and additional susceptibility loci playing minor roles.", " Traditional RET germline mutations account for a small subset of Hirschsprung disease patients, but several studies have shown that there is a specific haplotype of RET associated with the sporadic forms of Hirschsprung disease.", "PURPOSE: The RET proto-oncogene is considered to be the major susceptibility gene involved in Hirschsprung disease.", "The RET proto-oncogene is the major gene involved in the pathogenesis of Hirschsprung (HSCR), a complex genetic disease characterized by lack of ganglia along variable lengths of the gut.", "While rare variants (RVs) in the coding sequence (CDS) of several genes involved in ENS development lead to disease, the association of common variants (CVs) with HSCR has only been reported for RET (the major HSCR gene) and NRG1.", "The rearranged during transfection (RET) proto-oncogene is the major susceptibility gene for Hirschsprung disease, and germline mutations in RET have been reported in up to 50% of the inherited forms of Hirschsprung disease and in 15-20% of sporadic cases of Hirschsprung disease.", "The major gene for Hirschsprung disease (HSCR) encodes the receptor tyrosine kinase RET. In a study of 690 European- and 192 Chinese-descent probands and their parents or controls, we demonstrate the ubiquity of a >4-fold susceptibility from a C-->T allele (rs2435357: p = 3.9 x 10(-43) in European ancestry; p = 1.1 x 10(-21) in Chinese samples) that probably arose once within the intronic RET enhancer MCS+9.7.", "Hirschsprung disease (HSCR), a developmental disorder characterized by the absence of enteric neurons in distal segments of the gut, shows a complex pattern of inheritance, with the RET protooncogene acting as a major gene and additional susceptibility loci playing minor roles.", "BACKGROUND: The RET gene encodes a tyrosine kinase receptor involved in different human neurocristopathies, such as specific neuroendocrine tumours and Hirschsprung disease (HSCR).", "The first major susceptibility gene for Hirschsprung disease is the RET proto-oncogene on 10q11.2.", "The developmental abnormalities apparent in these mice, together with the observation that the major tissues affected in MEN 2 and Hirschsprung disease have a common origin in the embryonal neural crest, suggest that RET encodes a receptor for a developmental regulator involved in the genesis of a variety of neural crest derivatives, and in the organogenesis of the kidney.", "RET is the major gene involved in HSCR.", "Recent advances show that the RET gene is a major locus involved in the pathogenesis of HSCR.", "Although with several genes involved in its pathogenesis, the major HSCR gene is the RET proto-oncogene.", "In this model, a major gene, RET, is involved in most if not all cases of isolated (i.e., nonsyndromic) HSCR, in conjunction with other autosomal susceptibility loci under a multiplicative model.", "The RET proto-oncogene is the major gene involved in the pathogenesis of Hirschsprung (HSCR), a complex genetic disease characterized by lack of ganglia along variable lengths of the gut", "The RET proto-oncogene is the major gene involved in the complex genetics of Hirschsprung disease (HSCR), or aganglionic megacolon, showing causative loss-of-function mutations in 15-30% of the sporadic cases", "The RET proto-oncogene is considered to be the major susceptibility gene involved in Hirschsprung disease", "Analysis of the RET gene, the major gene involved in HSCR susceptibility, revealed neither linkage nor mutations", "RET is the major gene involved in HSCR", "Although with several genes involved in its pathogenesis, the major HSCR gene is the RET proto-oncogene", "While rare variants (RVs) in the coding sequence (CDS) of several genes involved in ENS development lead to disease, the association of common variants (CVs) with HSCR has only been reported for RET (the major HSCR gene) and NRG1", "The rearranged during transfection (RET) proto-oncogene is the major susceptibility gene for Hirschsprung disease, and germline mutations in RET have been reported in up to 50% of the inherited forms of Hirschsprung disease and in 15-20% of sporadic cases of Hirschsprung disease", "Recent advances show that the RET gene is a major locus involved in the pathogenesis of HSCR", "In this model, a major gene, RET, is involved in most if not all cases of isolated (i.e., nonsyndromic) HSCR, in conjunction with other autosomal susceptibility loci under a multiplicative model", "We report on mutation analysis of five genes involved in the receptor tyrosine kinase (RET) or the endothelin-signalling pathways in 28 sporadic Japanese patients with Hirschsprung disease", "In addition to mutations in the RET and EDNRB genes, embryonic environmental factors and/or other genetic factors appear to be involved in the development of Hirschsprung disease", "The RET gene is the major HSCR gene, although reduced penetrance of RET mutations and variable expression of HSCR phenotype indicates that more than one gene is required" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/12865274", "http://www.ncbi.nlm.nih.gov/pubmed/22574178", "http://www.ncbi.nlm.nih.gov/pubmed/16816022", "http://www.ncbi.nlm.nih.gov/pubmed/22131258", "http://www.ncbi.nlm.nih.gov/pubmed/23400839", "http://www.ncbi.nlm.nih.gov/pubmed/17108762", "http://www.ncbi.nlm.nih.gov/pubmed/16986122", "http://www.ncbi.nlm.nih.gov/pubmed/23372769", "http://www.ncbi.nlm.nih.gov/pubmed/9727738", "http://www.ncbi.nlm.nih.gov/pubmed/16877807", "http://www.ncbi.nlm.nih.gov/pubmed/16441254", "http://www.ncbi.nlm.nih.gov/pubmed/22584707", "http://www.ncbi.nlm.nih.gov/pubmed/16448984", "http://www.ncbi.nlm.nih.gov/pubmed/10664228", "http://www.ncbi.nlm.nih.gov/pubmed/10790203", "http://www.ncbi.nlm.nih.gov/pubmed/20598273", "http://www.ncbi.nlm.nih.gov/pubmed/22344793", "http://www.ncbi.nlm.nih.gov/pubmed/17397038", "http://www.ncbi.nlm.nih.gov/pubmed/21995290", "http://www.ncbi.nlm.nih.gov/pubmed/18285831", "http://www.ncbi.nlm.nih.gov/pubmed/17965226", "http://www.ncbi.nlm.nih.gov/pubmed/7883791" ]

[]

[ "http://www.disease-ontology.org/api/metadata/DOID:10487", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D006627", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D051096" ]

[ "Small-cell lung cancer is most commonly associated with Lambert-Eaton syndrome. Case reports suggest that other non-small-cell lung cancer types, such as large-cell neuroendocrine carcinoma and squamous cell carcinoma, can be also very rarely associated this syndrome." ]

[ "small-cell lung cancer" ]

[ "The autoantibodies implicated in the Lambert-Eaton myasthenic syndrome (LES), which are known to inhibit ICa and INa in bovine adrenal chromaffin cells, also significantly inhibited INa in SCLC cells.", "These results indicate that (i) action potentials in human SCLC cells result from the regenerative increase in voltage-gated Na+ channel conductance; (ii) fundamental characteristics of SCLC Na+ channels are the same as the classical sodium channels found in a variety of excitable cells; and (iii) in some LES patients, SCLC Na+ channels are an additional target of the pathological IgG present in the patients' sera.", "Clinical features were those of LES and occurred insidiously in this 68-year old man: proximal weakness predominant in the lower limbs, generalized areflexia, dryness of the mouth and partial right eye palsy. Investigations disclosed a small cell lung cancer.", "Voltage-gated Ca2+ channels may be important to the secretion of ectopic hormones and the etiology and pathogenesis of Lambert-Eaton syndrome, an autoimmune disorder of the motor nerve terminal in which autoantibodies directed against voltage-gated Ca2+ channels are produced.", "Lambert-Eaton syndrome is a myasthenia-like syndrome of paraneoplastic origin which is often associated with anaplastic small-cell lung cancer.", "Small-cell lung cancer (SCLC) is the most common cause of LES.", "We report an unusual case of LES associated with large-cell neuroendocrine carcinoma (LCNEC) of the lung.", "The Lambert-Eaton syndrome is caused by antibodies against voltage-gated calcium channels and often occurs in patients with small cell lung cancer.", "A 53 year-old heavy smoker presented with a Lambert-Eaton myasthenic syndrome (LEMS). Bronchoscopy was normal but radiological examinations revealed a lymph node in site 4R. The pathological diagnosis after mediastinoscopy was negative. Twenty-five months later, an opacity on chest X-ray led to a biopsy which revealed a squamous cell carcinoma.", "LEMS is generally associated with small cell lung cancer occurring in three percent of cases.", "However, the case that we report shows the unusual association of LEMS with non small-cell lung cancer and highlights the difficulties associated in the management of this condition.", "LEMS has a high degree of coincidence (approximately 60%) with small cell lung cancer; the remaining 40% of patients with LEMS have no detectable tumor.", "BACKGROUND: To enhance the acknowledgement of Lambert-Eaton syndrome in patients with small cell lung cancer.", "There were 10 cases of Lambert-Eaton syndrome in 332 pathologically diagnosed small cell lung cancer", "Treatment of small cell lung cancer may improve the symptoms of Lambert-Eaton syndrome", "Improving the recognition of Lambert-Eaton syndrome may be helpful to identify early small cell lung cancer and improve the prognosis,as the symptom of muscular weakness usually appears early before the diagnosis of small cell lung cancer.", "The Lambert Eaton syndrome is a paraneoplastic manifestation of small-cell lung cancer in 50% of the cases unlike generalized myasthenia which apparently is never associated with small-cell lung cancer.", "Paraneoplastic Lambert-Eaton myasthenia syndrome is presented in two cases with small cell lung cancer.", "Human small-cell lung cancer (SCLC) cells are believed to express the antigens responsible for the production of pathological antibodies in the Lambert-Eaton syndrome (LES), a Ca2+ channel disorder in which quantal transmitter release from the motor nerve terminal is impaired.", "Lambert-Eaton myasthenic syndrome (LEMS) is a paraneoplastic autoimmune disorder caused by an IgG-mediated reduction in number of presynaptic voltage-gated calcium channels (VGCC) at the neuromuscular junction. In at least 50% of cases, the stimulus for antibody production may be VGCC on small cell lung cancer (SCLC)", "Also, there was no obvious band pattern distinguishing patients with LES from those with LES and concurrent SCLC.", "The cancer associated with LEMS was small-cell lung carcinoma (SCLC) in 15 cases and epidermoid lung carcinoma in 3 cases.", "Etiology of this disease is uncertain but in view of its frequent association with small cell lung cancer, this specific type of neoplasm may be implicated in the initiation of autoimmune response.", "Recent studies indeed support the possibility that the antigenic stimulus in the neoplastic form of LES may arise from voltage-dependent Ca2+ channels found in the lung cancer cells.", "In the majority of LEMS patients, those having detectable tumor, the disease is thought to occur as a result of immune response directed initially against voltage-gated Ca2+ channels found on the lung tumor cells.", "Radiological, bronchoscopic and histological investigations revealed small-cell lung cancer, and neurophysiological investigations confirmed a diagnosis of LEMS.", "Physicians need to be aware that patients may develop PCD and LEMS associated with anti-VGCC antibody caused by small cell lung cancer, and a mass survey should be conducted and careful examinations performed.", "Biopsy revealed small cell lung cancer (SCLC) indicating the importance of repeated chest CT in LEMS even when an existing autoimmune-like disease and negative CT may suggest an autoimmune origin.", "BACKGROUND: Neuromuscular symptoms in patients with Lambert-Eaton myasthenic syndrome (LEMS) and a small cell lung cancer (SCLC) develop more rapidly than in LEMS patients without a SCLC.", "The detection of SOX1 antibodies in patients with Lambert-Eaton myasthenic syndrome (LEMS) predicts the presence of small cell lung cancer and may be used to follow more closely those LEMS patients with no evidence of cancer at the initial workup.", "The presence of a particular symptom associated with LEMS did not predict the presence of SCLC, but in patients with rapidly progressive LEMS the possibility of underlying lung cancer should be of particular concern.", "We report a case of small-cell lung cancer (SCLC) presenting with LEMS and ventilatory failure in a 67-year-old man who initially presented with progressive limb weakness for 6 months and tachypnea with shallow breathing for 1 week.", "Using this protein, we demonstrated that anti-beta-subunit antibodies are present in the sera of 23% of LEMS patients and only, in low titer, in 2% of small cell lung cancer patients without LEMS.", "The gene encoding the beta 2 protein, first described as a Lambert-Eaton myasthenic syndrome (LEMS) antigen in humans, is found close to a region that undergoes chromosome rearrangements in small cell lung cancer, which occurs in association with LEMS.", "We then tested sera from 72 LEMS patients' 25 with proven small cell lung cancer (SCLC) and 66 healthy or other neurological, SCLC or autoimmune disease controls in an immunoprecipitation assay using 125I-omega-CmTx-labelled (P/Q-type) VGCCs in human cerebellar extract.", "In the majority of patients LEMS is associated with small cell lung cancer (SCLC).", "Patients with small cell lung cancer (SCLC) in particular may develop LEMS, and SCLC is very often detected in patients affected by LEMS.", "We present a 69-year-old woman who had preventive whole brain radiation after a diagnosis of paraneoplastic Lambert-Eaton syndrome related to small cell lung cancer Five months after radiation therapy, she developed radiation-induced leukoencephalopathy manifested by ataxia.", "Among the symptoms of lung cancer LEMS can be seen, but it is very rare.", "A patient with the Lambert-Eaton syndrome (LES) and small cell lung cancer developed respiratory failure several hours after verapamil was given." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/8568672", "http://www.ncbi.nlm.nih.gov/pubmed/18032743", "http://www.ncbi.nlm.nih.gov/pubmed/16100656", "http://www.ncbi.nlm.nih.gov/pubmed/9094058", "http://www.ncbi.nlm.nih.gov/pubmed/9254841", "http://www.ncbi.nlm.nih.gov/pubmed/2189179", "http://www.ncbi.nlm.nih.gov/pubmed/1339000", "http://www.ncbi.nlm.nih.gov/pubmed/1318636", "http://www.ncbi.nlm.nih.gov/pubmed/19803409", "http://www.ncbi.nlm.nih.gov/pubmed/18644631", "http://www.ncbi.nlm.nih.gov/pubmed/20392978", "http://www.ncbi.nlm.nih.gov/pubmed/8009147", "http://www.ncbi.nlm.nih.gov/pubmed/18841652", "http://www.ncbi.nlm.nih.gov/pubmed/20514935", "http://www.ncbi.nlm.nih.gov/pubmed/2833535", "http://www.ncbi.nlm.nih.gov/pubmed/1448671", "http://www.ncbi.nlm.nih.gov/pubmed/10486838", "http://www.ncbi.nlm.nih.gov/pubmed/7731034", "http://www.ncbi.nlm.nih.gov/pubmed/9538660", "http://www.ncbi.nlm.nih.gov/pubmed/20979723", "http://www.ncbi.nlm.nih.gov/pubmed/18506722", "http://www.ncbi.nlm.nih.gov/pubmed/3016531", "http://www.ncbi.nlm.nih.gov/pubmed/8186692", "http://www.ncbi.nlm.nih.gov/pubmed/15793845", "http://www.ncbi.nlm.nih.gov/pubmed/12632823", "http://www.ncbi.nlm.nih.gov/pubmed/1470196", "http://www.ncbi.nlm.nih.gov/pubmed/9484375", "http://www.ncbi.nlm.nih.gov/pubmed/15000529", "http://www.ncbi.nlm.nih.gov/pubmed/8387255", "http://www.ncbi.nlm.nih.gov/pubmed/17395141", "http://www.ncbi.nlm.nih.gov/pubmed/15767964" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D015624", "http://www.disease-ontology.org/api/metadata/DOID:3905", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D008175", "http://www.disease-ontology.org/api/metadata/DOID:0050214", "http://www.disease-ontology.org/api/metadata/DOID:1324" ]

[ "Lantibiotic compounds are ribosomally synthesized antimicrobial peptides against which bacteria are not able to produce resistance, hence making them a good alternative to antibiotics. It is interesting that low levels of resistance have been reported for lantibiotics compared with commercial antibiotics. Given that there are very few examples of naturally occurring lantibiotic resistance, attempts have been made to deliberately induce resistance phenotypes in order to investigate this phenomenon. Other general forms of resistance include the formation of spores or biofilms, which are a common mechanistic response to many classes of antimicrobials.", "One potentially interesting class of antimicrobials are the modified bacteriocins termed lantibiotics, which are bacterially produced, posttranslationally modified, lanthionine/methyllanthionine-containing peptides. Low levels of resistance have been reported for lantibiotics compared with commercial antibiotics. Nisin is the oldest and the most widely used lantibiotic, in food preservation, without having developed any significant resistance against it.", "One potentially interesting class of antimicrobials are the modified bacteriocins termed lantibiotics, which are bacterially produced, posttranslationally modified, lanthionine/methyllanthionine-containing peptides." ]

[ "Lantibiotics are post-translationally modified natural peptides containing lanthionine" ]

[ "One potentially interesting class of antimicrobials are the modified bacteriocins termed lantibiotics, which are bacterially produced, posttranslationally modified, lanthionine/methyllanthionine-containing peptides.", "low levels of resistance have been reported for lantibiotics compared with commercial antibiotics", "Mechanisms that hinder the action of lantibiotics are often innate systems that react to the presence of any cationic peptides/proteins or ones which result from cell well damage, rather than being lantibiotic specific.", "Lantibiotics are biologically active peptides produced by Gram-positive bacteria. ", "Lantibiotics are post-translationally modified, ribosomally synthesised antimicrobial peptides with a broad spectrum antimicrobial activity.", "Lantibiotic compounds are ribosomally synthesized antimicrobial peptides against which bacteria are not able to produce resistance, hence making them a good alternative to antibiotics.", "Lantibiotics are ribosomally synthesized peptide antibiotics that are posttranslationally modified to introduce (methyl)lanthionine bridges.", "Lantibiotics are defined as peptide antibiotics containing the unusual amino acids mesolanthionine, 3-methyllanthionine, dehydroalanine, and dehydrobutyrine.", "Lantibiotics are antibiotic peptides distinguished by the presence of the rare thioether amino acids lanthionine and/or methyllanthionine.", "Lantibiotics are ribosomally synthesized, post-translationally modified, peptide antibiotics containing unusual amino acids such as dehydrated amino acids and lanthionine.", "Lantibiotics are peptide antibiotics, realizing their unique secondary structure by posttranslational modifications, the most important one being the formation of the characteristic amino acid lanthionine.", "Lantibiotics are lanthionine-containing peptide antibiotics. ", "Lantibiotics, a group of lanthionine-containing peptides, display their antibiotic activity by combining different killing mechanisms within one molecule. ", "Lantibiotics are ribosomally synthesized as prepeptides, which are posttranslationally modified." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/12361237", "http://www.ncbi.nlm.nih.gov/pubmed/19009315", "http://www.ncbi.nlm.nih.gov/pubmed/21905643", "http://www.ncbi.nlm.nih.gov/pubmed/8264800", "http://www.ncbi.nlm.nih.gov/pubmed/24069959", "http://www.ncbi.nlm.nih.gov/pubmed/21470152", "http://www.ncbi.nlm.nih.gov/pubmed/19393544", "http://www.ncbi.nlm.nih.gov/pubmed/15044440", "http://www.ncbi.nlm.nih.gov/pubmed/23168402", "http://www.ncbi.nlm.nih.gov/pubmed/11945173", "http://www.ncbi.nlm.nih.gov/pubmed/25787977", "http://www.ncbi.nlm.nih.gov/pubmed/23475977", "http://www.ncbi.nlm.nih.gov/pubmed/1482192", "http://www.ncbi.nlm.nih.gov/pubmed/24621781", "http://www.ncbi.nlm.nih.gov/pubmed/24210177" ]

[]

[ "http://www.biosemantics.org/jochem#4275453", "http://www.biosemantics.org/jochem#4260744" ]

[ "Congenital cataracts, facial dysmorphism and peripheral neuropathy are three major features of the CCFDN syndrome. Other described signs and symptoms of the CCFDN syndrome include microcornea, microphthalmos, micropupil, floppy eyelid syndrome, pseudoptosis, nystagmus, congenital esotropia, impairment of distant visual acuity, ataxia, pyramidal signs, mild chorea, short stature, muscular atrophy, delayed early motor and intellectual development, hypogonadotrop hypogonadism, hypomyelination of the peripheral nervous system, serious complications related to general anaesthesia and parainfectious rhabdomyolysis." ]

[ "congenital cataracts", "facial dysmorphism", "peripheral neuropathy" ]

[ "Because of our experience in neuromuscular disorders, we choose six, frequent, autosomal recessive disorders for these clinical and genetic studies: hereditary motor and sensory neuropathy type Lom (HMSNL), hereditary motor and sensory neuropathy type Russe (HMSNR), congenital cataracts facial dysmorphism syndrome (CCFDN), limb-girdle muscular dystrophy 2C (LGMD2C), congenital myasthenic syndrome (CMS) and spinal muscular atrophy (SMA).", "The congenital cataracts facial dysmorphism neuropathy (CCFDN) syndrome (OMIM 604168) is a recently described autosomal recessive developmental disorder. ", "Congenital cataracts-facial dysmorphism-neuropathy syndrome (CCFDN, MIM: 604168), is a recently delineated neurogenetic disease causing recurrent episodes of rhabdomyolysis; prevention and early diagnosis of rhabdomyolysis should be part of the clinical management of the disease.", "Congenital Cataracts Facial Dysmorphism Neuropathy (CCFDN) syndrome is a complex developmental disorder of autosomal recessive inheritance. ", "OBJECTIVE: To determine the nature and course of ophthalmologic abnormalities in congenital cataracts facial dysmorphism neuropathy (CCFDN) syndrome in a genetically verified group of 9 patients.", "Congenital cataracts facial dysmorphism neuropathy (CCFDN) syndrome (OMIM 604168) is an autosomal recessive developmental disorder that occurs in an endogamous group of Vlax Roma (Gypsies; refs. 1-3). ", "The major differential diagnosis of MSS is the syndrome defined by congenital cataracts, facial dysmorphism and peripheral neuropathy (CCFDN), which is localised to 18qter.", "The CCFDN syndrome is a complex phenotype involving multiple systems, characterized by facial dysmorphism, congenital cataracts, microcorneae, delayed early motor and intellectual development, hypogonadotrop hypogonadism, hypomyelination of the peripheral nervous system, and serious complications related to general anaesthesia. ", "Developmental abnormalities include congenital cataracts and microcorneae, primary hypomyelination of the peripheral nervous system, impaired physical growth, delayed early motor and intellectual development, mild facial dysmorphism and hypogonadism. Para-infectious rhabdomyolysis is a serious complication reported in an increasing number of patients. ", "CONCLUSIONS: Early-onset congenital cataracts associated with microcornea, microphthalmos, and micropupil are essential ocular features of the CCFDN syndrome and are the first recognizable signs during early infancy. ", "All patients showed a peripheral, demyelinating neuropathy and varying degrees of ataxia. In the older patients, muscular atrophy in distal muscles and facial dysmorphism was evident. Early-onset bilateral congenital cataracts associated with microcornea, microphthalmos, and micropupil could be found in all patients. All children had floppy eyelid syndrome and pseudoptosis.", "All patients had syndrome-associated nystagmus and congenital esotropia. Distant visual acuity could be classified as severe to moderate impairment, whereas near visual acuity was much better (mild to moderate impairment).", "Because these families originated from the same genetically isolated founder population as did patients with congenital cataracts facial dysmorphism neuropathy (CCFDN) syndrome, and because the two syndromes have clinical manifestations in common, we hypothesized that the two related, albeit distinct, syndromes may represent clinical variants of a single genetic disorder. ", "Peripheral nerve abnormalities in the congenital cataracts facial dysmorphism neuropathy (CCFDN) syndrome.", "Congenital cataracts facial dysmorphism neuropathy (CCFDN) syndrome: a novel developmental disorder in Gypsies maps to 18qter.", "We propose to refer to the syndrome as congenital cataracts facial dysmorphism neuropathy (CCFDN). ", "The disorder has been termed the congenital cataracts facial dysmorphism neuropathy (CCFDN) syndrome to emphasize its salient features. ", "Associated neurological features are a moderate nonprogressive cognitive deficit in most affected individuals together with pyramidal signs and mild chorea in some. Accompanying nonneurological features include short stature, characteristic facial dysmorphism, and hypogonadotrophic hypogonadism. Nerve conduction studies suggest a hypomyelinating/demyelinating neuropathy, confirmed by nerve biopsy. ", "Congenital cataracts facial dysmorphism neuropathy (CCFDN) syndrome: a rare cause of parainfectious rhabdomyolysis.", "CONCLUSIONS: Early-onset congenital cataracts associated with microcornea, microphthalmos, and micropupil are essential ocular features of the CCFDN syndrome and are the first recognizable signs during early infancy.", "The disorder has been termed the congenital cataracts facial dysmorphism neuropathy (CCFDN) syndrome to emphasize its salient features.", "Because these families originated from the same genetically isolated founder population as did patients with congenital cataracts facial dysmorphism neuropathy (CCFDN) syndrome, and because the two syndromes have clinical manifestations in common, we hypothesized that the two related, albeit distinct, syndromes may represent clinical variants of a single genetic disorder.", "Congenital cataracts-facial dysmorphism-neuropathy syndrome (CCFDN, MIM: 604168), is a recently delineated neurogenetic disease causing recurrent episodes of rhabdomyolysis; prevention and early diagnosis of rhabdomyolysis should be part of the clinical management of the disease", "The major differential diagnosis of MSS is the syndrome defined by congenital cataracts, facial dysmorphism and peripheral neuropathy (CCFDN), which is localised to 18qter" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/25186864", "http://www.ncbi.nlm.nih.gov/pubmed/15234148", "http://www.ncbi.nlm.nih.gov/pubmed/17195938", "http://www.ncbi.nlm.nih.gov/pubmed/14512967", "http://www.ncbi.nlm.nih.gov/pubmed/11805249", "http://www.ncbi.nlm.nih.gov/pubmed/19070320", "http://www.ncbi.nlm.nih.gov/pubmed/17578274", "http://www.ncbi.nlm.nih.gov/pubmed/16939648", "http://www.ncbi.nlm.nih.gov/pubmed/14517542", "http://www.ncbi.nlm.nih.gov/pubmed/10439962", "http://www.ncbi.nlm.nih.gov/pubmed/10442556", "http://www.ncbi.nlm.nih.gov/pubmed/10360766" ]

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[ "Several survival studies showed that professional athletes has higher longevity than general population. These epidemiological data matches the evidences that long-term endurance training induces in elderly subjects an increased HRV and a higher exercise working capacity, which are well-established predictors of cardiovascular and overall mortality, and also telomere length." ]

[ "yes" ]

[ "We found a very significant increase in average longevity (17%) of the cyclists when compared with the general population. The age at which 50% of the general population died was 73.5 vs. 81.5 years in Tour de France participants. Our major finding is that repeated very intense exercise prolongs life span in well trained practitioners.", "Competitive exercise does not induce cardiac damage in individuals with healthy hearts, but does induce physiological functional and structural cardiac adaptations which have positive effects on life expectancy.", "Medallists lived an average of 2.8 years longer than controls. Medallists in eight of the nine country groups had a significant survival advantage compared with controls. Gold, silver, and bronze medallists each enjoyed similar sized survival advantages. Medallists in endurance sports and mixed sports had a larger survival advantage over controls at 30 years (1.13, 1.09 to 1.17; 1.11, 1.09 to 1.13) than that of medallists in power sports (1.05, 1.01 to 1.08). CONCLUSIONS: Olympic medallists live longer than the general population, irrespective of country, medal, or sport. This study was not designed to explain this effect, but possible explanations include genetic factors, physical activity, healthy lifestyle, and the wealth and status that come with international sporting glory.", "Long-term endurance training induces in elderly subjects an increased HRV and a higher exercise working capacity, which are well-established predictors of cardiovascular and overall mortality.", "Sports activity in adolescents and young adults was associated with an increased risk of SD, both in males and females. Sports, per se, was not a cause of the enhanced mortality, but it triggered SD in those athletes who were affected by cardiovascular conditions predisposing to life-threatening ventricular arrhythmias during physical exercise." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/21925040", "http://www.ncbi.nlm.nih.gov/pubmed/14662259", "http://www.ncbi.nlm.nih.gov/pubmed/12832429", "http://www.ncbi.nlm.nih.gov/pubmed/16355084", "http://www.ncbi.nlm.nih.gov/pubmed/17436206", "http://www.ncbi.nlm.nih.gov/pubmed/23300766", "http://www.ncbi.nlm.nih.gov/pubmed/23241272", "http://www.ncbi.nlm.nih.gov/pubmed/21477204", "http://www.ncbi.nlm.nih.gov/pubmed/12919770", "http://www.ncbi.nlm.nih.gov/pubmed/17036189", "http://www.ncbi.nlm.nih.gov/pubmed/21435018", "http://www.ncbi.nlm.nih.gov/pubmed/22413946", "http://www.ncbi.nlm.nih.gov/pubmed/23450998", "http://www.ncbi.nlm.nih.gov/pubmed/19575156", "http://www.ncbi.nlm.nih.gov/pubmed/21618162", "http://www.ncbi.nlm.nih.gov/pubmed/2279154", "http://www.ncbi.nlm.nih.gov/pubmed/23241269", "http://www.ncbi.nlm.nih.gov/pubmed/22332442" ]

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