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HiTZ zentroa 49

[ "Coding sequence mutations in RET, GDNF, EDNRB, EDN3, and SOX10 are involved in the development of Hirschsprung disease. The majority of these genes was shown to be related to Mendelian syndromic forms of Hirschsprung's disease, whereas the non-Mendelian inheritance of sporadic non-syndromic Hirschsprung disease proved to be complex; involvement of multiple loci was demonstrated in a multiplicative model." ]

[]

[ "Hirschsprung disease (HSCR) is a multifactorial, non-mendelian disorder in which rare high-penetrance coding sequence mutations in the receptor tyrosine kinase RET contribute to risk in combination with mutations at other genes", "In this study, we review the identification of genes and loci involved in the non-syndromic common form and syndromic Mendelian forms of Hirschsprung's disease. The majority of the identified genes are related to Mendelian syndromic forms of Hirschsprung's disease. The non-Mendelian inheritance of sporadic non-syndromic Hirschsprung's disease proved to be complex; involvement of multiple loci was demonstrated in a multiplicative model", "Coding sequence mutations in e.g. RET, GDNF, EDNRB, EDN3, and SOX10 lead to long-segment (L-HSCR) as well as syndromic HSCR but fail to explain the transmission of the much more common short-segment form (S-HSCR). Furthermore, mutations in the RET gene are responsible for approximately half of the familial and some sporadic cases, strongly suggesting, on the one hand, the importance of non-coding variations and, on the other hand, that additional genes involved in the development of the enteric nervous system still await their discovery", "For almost all of the identified HSCR genes incomplete penetrance of the HSCR phenotype has been reported, probably due to modifier loci. Therefore, HSCR has become a model for a complex oligo-/polygenic disorder in which the relationship between different genes creating a non-mendelian inheritance pattern still remains to be elucidated", " Hirschsprung disease (HSCR) is a multifactorial, non-mendelian disorder in which rare high-penetrance coding sequence mutations in the receptor tyrosine kinase RET contribute to risk in combination with mutations at other genes.", " The inheritance of Hirschsprung disease is generally consistent with sex-modified multifactorial inheritance with a lower threshold of expression in males.", "Hirschsprung disease (HSCR) is a multifactorial, non-mendelian disorder in which rare high-penetrance coding sequence mutations in the receptor tyrosine kinase RET contribute to risk in combination with mutations at other genes.", "Differential contributions of rare and common, coding and noncoding Ret mutations to multifactorial Hirschsprung disease liability.", "BACKGROUND: 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.", "In the etiology of Hirschsprung disease various genes play a role; these are: RET, EDNRB, GDNF, EDN3 and SOX10, NTN3, ECE1, Mutations in these genes may result in dominant, recessive or multifactorial patterns of inheritance.", "Chromosomal and related Mendelian syndromes associated with Hirschsprung's disease.", "The majority of the identified genes are related to Mendelian syndromic forms of Hirschsprung's disease", "In the etiology of Hirschsprung disease various genes play a role; these are: RET, EDNRB, GDNF, EDN3 and SOX10, NTN3, ECE1, Mutations in these genes may result in dominant, recessive or multifactorial patterns of inheritance", "On the basis of a skewed sex-ratio (M/F = 4/1) and a risk to relatives much higher than the incidence in the general population, HSCR has long been regarded as a sex-modified multifactorial disorder", "The inheritance of Hirschsprung disease is generally consistent with sex-modified multifactorial inheritance with a lower threshold of expression in males", "The non-Mendelian inheritance of sporadic non-syndromic Hirschsprung's disease proved to be complex; involvement of multiple loci was demonstrated in a multiplicative model" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/15829955", "http://www.ncbi.nlm.nih.gov/pubmed/6650562", "http://www.ncbi.nlm.nih.gov/pubmed/12239580", "http://www.ncbi.nlm.nih.gov/pubmed/21995290", "http://www.ncbi.nlm.nih.gov/pubmed/23001136", "http://www.ncbi.nlm.nih.gov/pubmed/15617541", "http://www.ncbi.nlm.nih.gov/pubmed/8896569", "http://www.ncbi.nlm.nih.gov/pubmed/20598273" ]

[]

[ "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=D020412", "http://www.disease-ontology.org/api/metadata/DOID:11372" ]

[ "The 7 known EGFR ligands are: epidermal growth factor (EGF), betacellulin (BTC), epiregulin (EPR), heparin-binding EGF (HB-EGF), transforming growth factor-α [TGF-α], amphiregulin (AREG) and epigen (EPG)." ]

[ "epidermal growth factor", "betacellulin", "epiregulin", "heparin-binding epidermal growth factor", "transforming growth factor-α", "amphiregulin", "epigen" ]

[ "the epidermal growth factor receptor (EGFR) ligands, such as epidermal growth factor (EGF) and amphiregulin (AREG)", " EGFR ligands epidermal growth factor (EGF), amphiregulin (AREG) and transforming growth factor alpha (TGFα)", " EGFR and its ligand EGF ", "Among EGFR ligands, heparin-binding EGF-like growth factor, TGF-α and Betacellulin (BTC) are produced in the tumor microenvironment of FDC-S at RNA level. ", ". Plasma amphiregulin (AR), epidermal growth factor (EGF), transforming growth factor-α, and heparin binding-EGF were assessed by ELISA in 45 chemorefractory mCRC patients", "Among EGFR ligands, heparin-binding epidermal growth factor (HB-EGF)", " Of the six known EGFR ligands, transforming growth factor alpha (TGFα) was expressed more highly in triple-negative breast tumors than in tumors of other subtypes.", "the 7 known EGFR ligands (EGF, betacellulin, epiregulin, heparin-binding EGF, transforming growth factor-α [TGF-α], amphiregulin, and epigen) ", "EGFR ligands based on the two affinity classes: EGF>HB-EGF>TGF-α>BTC>EPR>EPG>AR", "In this article, however, we demonstrate that PEPD directly binds to and activates epidermal growth factor receptor (EGFR),", "four EGFR ligands (AR, HB-EGF, TGF-α, and EREG) ", "Epidermal growth factor (EGF) family peptides are ligands for the EGF receptor (EGFR). ", "oluble amphiregulin (AR), transforming growth factor alpha (TGFα), neuregulin 2 beta, and epigen stimulate greater EGFR coupling to cell proliferation and DNA synthesis than do EGF, betacellulin, heparin-binding EGF-like growth factor, and epiregulin", "Here, we demonstrate that histamine releases 2 EGFR ligands, amphiregulin and heparin-binding epidermal growth factor-like growth factor (HB-EGF), from airway epithelial cells.", "mammalian EGFR ligands including EGF, TGF-α (TGFα), amphiregulin (AREG), heparin-binding EGF-like growth factor (HB-EGF), betacellulin, epiregulin, and epigen." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/23959273", "http://www.ncbi.nlm.nih.gov/pubmed/21514161", "http://www.ncbi.nlm.nih.gov/pubmed/23787814", "http://www.ncbi.nlm.nih.gov/pubmed/23888072", "http://www.ncbi.nlm.nih.gov/pubmed/23821377", "http://www.ncbi.nlm.nih.gov/pubmed/24124521", "http://www.ncbi.nlm.nih.gov/pubmed/22260327", "http://www.ncbi.nlm.nih.gov/pubmed/24204699", "http://www.ncbi.nlm.nih.gov/pubmed/24323361", "http://www.ncbi.nlm.nih.gov/pubmed/23089711", "http://www.ncbi.nlm.nih.gov/pubmed/23399900", "http://www.ncbi.nlm.nih.gov/pubmed/23382875", "http://www.ncbi.nlm.nih.gov/pubmed/23729230", "http://www.ncbi.nlm.nih.gov/pubmed/23212918", "http://www.ncbi.nlm.nih.gov/pubmed/23099994", "http://www.ncbi.nlm.nih.gov/pubmed/22247333" ]

[ { "p": "http://purl.uniprot.org/core/encodedBy", "s": "http://purl.uniprot.org/uniprot/Q9QX70", "o": "http://linkedlifedata.com/resource/#_5139515837300022" }, { "p": "http://www.w3.org/2004/02/skos/core#prefLabel", "s": "http://linkedlifedata.com/resource/#_5139515837300022", "o": "Egfr" }, { "p": "http://www.w3.org/2004/02/skos/core#exactMatch", "s": "http://purl.uniprot.org/intact/EBI-1256812", "o": "http://purl.uniprot.org/uniprot/Q9QX70" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://purl.uniprot.org/intact/EBI-1256812", "o": "Egfr" } ]

[ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0005154", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0007176", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0005488", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0042058", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D018773", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D008024", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0045741", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0007173", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0005006", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0007175", "http://www.uniprot.org/uniprot/EGFR_HUMAN", "http://www.uniprot.org/uniprot/EGFR_CHICK" ]

[ "Yes, papilin is a secreted protein" ]

[ "yes" ]

[ "Using expression analysis, we identify three genes that are transcriptionally regulated by HLH-2: the protocadherin cdh-3, and two genes encoding secreted extracellular matrix proteins, mig-6/papilin and him-4/hemicentin. ", "We found that mig-6 encodes long (MIG-6L) and short (MIG-6S) isoforms of the extracellular matrix protein papilin, each required for distinct aspects of DTC migration. Both MIG-6 isoforms have a predicted N-terminal papilin cassette", "apilins are homologous, secreted extracellular matrix proteins which share a common order of protein domains. ", "The TSR superfamily is a diverse family of extracellular matrix and transmembrane proteins, many of which have functions related to regulating matrix organization, cell-cell interactions and cell guidance. This review samples some of the contemporary literature regarding TSR superfamily members (e.g. F-spondin, UNC-5, ADAMTS, papilin, and TRAP) where specific functions are assigned to the TSR domains.", "Papilins are extracellular matrix proteins ", "Papilin is an extracellular matrix glycoprotein ", " Collagen IV, laminin, glutactin, papilin, and other extracellular matrix proteins were made primarily by hemocytes and were secreted into the medium. ", "A sulfated glycoprotein was isolated from the culture media of Drosophila Kc cells and named papilin." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/3320045", "http://www.ncbi.nlm.nih.gov/pubmed/7515725", "http://www.ncbi.nlm.nih.gov/pubmed/20805556", "http://www.ncbi.nlm.nih.gov/pubmed/19297413", "http://www.ncbi.nlm.nih.gov/pubmed/19724244", "http://www.ncbi.nlm.nih.gov/pubmed/15094122", "http://www.ncbi.nlm.nih.gov/pubmed/12666201", "http://www.ncbi.nlm.nih.gov/pubmed/21784067", "http://www.ncbi.nlm.nih.gov/pubmed/11076767", "http://www.ncbi.nlm.nih.gov/pubmed/15094110" ]

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[]

[ "Long non coding RNAs appear to be spliced through the same pathway as the mRNAs" ]

[ "yes" ]

[ "Our analyses indicate that lncRNAs are generated through pathways similar to that of protein-coding genes, with similar histone-modification profiles, splicing signals, and exon/intron lengths.", "For alternative exons and long noncoding RNAs, splicing tends to occur later, and the latter might remain unspliced in some cases.", "bosome-mapping data to identify lncRNAs of Caenorhabditis elegans. We found 170 long intervening ncRNAs (lincRNAs), which had single- or multiexonic structures that did not overlap protein-coding transcripts, and about sixty antisense lncRNAs (ancRNAs), which were complementary to protein-coding transcripts", "We introduce an approach to predict spliced lncRNAs in vertebrate genomes combining comparative genomics and machine learning.", "Owing to similar alternative splicing pattern to mRNAs, the concept of lncRNA genes was put forward to help systematic understanding of lncRNAs. ", "Our synthesis of recent studies suggests that neither size, presence of a poly-A tail, splicing, direction of transcription, nor strand specificity are of importance to lncRNA function." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/22955988", "http://www.ncbi.nlm.nih.gov/pubmed/22955974", "http://www.ncbi.nlm.nih.gov/pubmed/24285305", "http://www.ncbi.nlm.nih.gov/pubmed/22707570", "http://www.ncbi.nlm.nih.gov/pubmed/21622663", "http://www.ncbi.nlm.nih.gov/pubmed/24106460" ]

[]

[ "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=D062085" ]

[ "Receptor activator of nuclear factor κB ligand (RANKL) is a cytokine predominantly secreted by osteoblasts." ]

[ "yes" ]

[ "Osteoprotegerin (OPG) is a soluble secreted factor that acts as a decoy receptor for receptor activator of NF-κB ligand (RANKL) ", "Osteoprotegerin (OPG) is a secreted glycoprotein and a member of the tumor necrosis factor receptor superfamily. It usually functions in bone remodeling, by inhibiting osteoclastogenesis through interaction with a receptor activator of the nuclear factor κB (RANKL).", "e RANKL/OPG ratio secreted by osteoblasts increased and RANK expression by osteoclasts increased, leading to increased osteoclastogenesis", "Osteoprotegerin (OPG) is an essential secreted protein in bone turnover due to its role as a decoy receptor for the Receptor Activator of Nuclear Factor-kB ligand (RANKL) in the osteoclasts, thus inhibiting their differentiation", "We identify a TNFSF11 transcript variant that extends the originally identified transcript encoding secreted RANKL.", "Activated human T cells express alternative mRNA transcripts encoding a secreted form of RANKL.", "OPG, on the other hand, is secreted by osteoblast as a decoy receptor for RANKL, prevents RANKL from binding to RANK and thus prevents bone resorption", "Receptor activator of nuclear factor κB ligand (RANKL) and osteoprotegerin (OPG) are cytokines predominantly secreted by osteoblasts and play a central role in differentiation and functional activation of osteoclasts", "Although B. abortus-activated T cells actively secreted the pro-osteoclastogenic cytokines RANKL and IL-17, osteoclastogenesis depended on IL-17, because osteoclast generation induced by Brucella-activated T cells was completely abrogated when these cells were cultured with BMMs from IL-17 receptor knockout mice. ", " osteoclastogenesis and bone destruction in autoimmune arthritis. We isolated human fibroblasts from RA, pyrophosphate arthropathy (PPA) and osteoarthritis (OA) patients and analyzed their RANKL/OPG expression profile and the capacity of their secreted factors to induce osteoclastogenesis.", "Osteoprotegerin (OPG) and receptor activator of nuclear factor κB ligand (RANKL) are cytokines predominantly secreted by osteoblasts and play critical roles in the differentiation and function of osteoclasts. " ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/22948539", "http://www.ncbi.nlm.nih.gov/pubmed/23698708", "http://www.ncbi.nlm.nih.gov/pubmed/23827649", "http://www.ncbi.nlm.nih.gov/pubmed/22901753", "http://www.ncbi.nlm.nih.gov/pubmed/21618594", "http://www.ncbi.nlm.nih.gov/pubmed/23835909", "http://www.ncbi.nlm.nih.gov/pubmed/23632157", "http://www.ncbi.nlm.nih.gov/pubmed/24265865", "http://www.ncbi.nlm.nih.gov/pubmed/24267510", "http://www.ncbi.nlm.nih.gov/pubmed/22867712" ]

[]

[ "http://www.uniprot.org/uniprot/TNF11_RAT", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D015870", "http://www.uniprot.org/uniprot/TNF11_HUMAN" ]

[ "There are not reported data indicating that metformin interferes with thyroxine absorption" ]

[ "no" ]

[]

[ "http://www.ncbi.nlm.nih.gov/pubmed/23264396", "http://www.ncbi.nlm.nih.gov/pubmed/21633823", "http://www.ncbi.nlm.nih.gov/pubmed/23554450", "http://www.ncbi.nlm.nih.gov/pubmed/23244059", "http://www.ncbi.nlm.nih.gov/pubmed/21041167", "http://www.ncbi.nlm.nih.gov/pubmed/21748540", "http://www.ncbi.nlm.nih.gov/pubmed/23072197", "http://www.ncbi.nlm.nih.gov/pubmed/21468525", "http://www.ncbi.nlm.nih.gov/pubmed/23154888", "http://www.ncbi.nlm.nih.gov/pubmed/21435090" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013974", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D008687", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D000042" ]

[ "miR-200a, miR-100, miR-141, miR-200b, miR-200c, miR-203, miR-510, miR-509-5p, miR-132, miR-26a, let-7b, miR-145, miR-182, miR-152, miR-148a, let-7a, let-7i, miR-21, miR-92 and miR-93 could be used as potential biomarkers for epithelial ovarian cancer." ]

[ "let-7a", "let-7b", "let-7i", "miR-21", "miR-26a", "miR-92", "miR-93", "miR-100", "miR-132", "miR-141", "miR-145", "miR-148a", "miR-152", "miR-182", "miR-200a", "miR-200b", "miR-200c", "miR-203", "miR-509-5p", "miR-510" ]

[ "Finally, five promising differentially miRNAs (miR-200a, miR-100, miR-141, miR-200b, and miR-200c) were reported with the consistent direction in four or more studies. MiR-200a, miR-200b, miR-200c, and miR-141, all of them belong to miR-200 family, were reported with consistently up-regulated in at least 4 studies, whereas miR-100 was reported with down-regulated in 4 studies", "Upregulation of microRNA-203 is associated with advanced tumor progression and poor prognosis in epithelial ovarian cancer", "multivariate analysis showed that the status of miR-203 expression was an independent predictor for both overall survival and progression-free survival in EOC. These findings provide the convincing evidence for the first time that the upregulation of miR-203 may serve as a novel molecular marker to predict the aggressive tumor progression and unfavorable prognosis of EOC patients", "Some, but not all, of the data indicated that the miR-200 family was dysregulated in a variety of malignancies. In this study, we demonstrated that miR-200a and E-cadherin were significantly upregulated in EOC compared to benign epithelial ovarian cysts and normal ovarian tissues", "There was a significantly positive correlation between miR-200a and E-cadherin in EOC. The biphasic expression pattern suggested that miR-200a levels may serve as novel biomarkers for the early detection of EOC, and miR-200a and E-cadherin are candidate targets for the development of new treatment modalities against ovarian cancer", "Kaplan-Meier analysis showed low miR-510 expression, low miR-509-5p expression, and advanced FIGO stage, and chemotherapy resistance were significantly associated with poorer overall survival (P < 0.05). Our results suggest that miRNAs may play a role in the progression of OSC, and miR-510 and miR-509-5p may be considered novel-candidate clinical biomarkers for predicting OSC outcome", "The qRT-PCR results showed that miR-510, miR-509-5p, and miR-508-3p were significantly downregulated and that miR-483-5p was upregulated in stage III OSC compared with stage I, which was consistent with the microarray results", "In this study, we examined serum miR-21 levels in epithelial ovarian cancer (EOC) patients, and explored its association with clinicopathological factors and prognosis. The results showed significantly higher serum miR-21 levels in EOC patients than in healthy controls. In addition, increased serum miR-21 expression was correlated with advanced FIGO stage, high tumor grade, and shortened overall survival. These findings indicate that serum miR-21 may serve as a novel diagnostic and prognostic marker, and be used as a therapeutic target for the treatment of EOC", "Identification of serum microRNA-21 as a biomarker for early detection and prognosis in human epithelial ovarian cancer", "Serum miR-132, miR-26a, let-7b, and miR-145 could be considered as potential candidates as novel biomarkers in serous ovarian cancer.", "Among the miRNAs that showed a consistent regulation tendency through all specimens and showed more than a 2-fold difference in serum, 5 miRNAs (miR-132, miR-26a, let-7b, miR-145, and miR-143) were determined as the 5 most markedly down-regulated miRNAs in the serum from ovarian cancer patients with respect to those of controls. Four miRNAs (miR-132, miR-26a, let-7b, and miR-145) out of 5 selected miRNAs were significantly underexpressed in the serum of ovarian cancer patients in qRT-PCR", " microRNA (miR)-182, miR-200a, miR-200b and miR-200c were highly overexpressed in the SEOC cell lines relative to normal human ovarian surface epithelial cells and were assessed in RNA extracted from serum as candidate biomarkers", "Together, these results suggest that low miR-100 expression may be an independent poor prognostic factor and miR-100 can function as a tumor suppressor by targeting PLK1 in human EOCs", "Prognostic implications of microRNA-100 and its functional roles in human epithelial ovarian cancer", "Taken together, miR-152 and miR-148a may be involved in the carcinogenesis of ovarian cancer through deregulation of cell proliferation. They may be novel biomarkers for early detection or therapeutic targets of ovarian cancer", "MicroRNA let-7a: a potential marker for selection of paclitaxel in ovarian cancer management", " The study suggests that the beneficial impact of the addition of paclitaxel on EOC survival was significantly linked to let-7a levels, and that miRNAs such as let-7a may be a useful marker for selection of chemotherapeutic agents in EOC management", "miR-200c has potential as a predictor of survival, and is a biomarker of relapse, in stage I EOC", "MicroRNA microarray identifies Let-7i as a novel biomarker and therapeutic target in human epithelial ovarian cancer", " our results strongly suggest that let-7i might be used as a therapeutic target to modulate platinum-based chemotherapy and as a biomarker to predict chemotherapy response and survival in patients with ovarian cancer", "miRNAs-21, 92 and 93 are known oncogenes with therapeutic and biomarker potential", "Serum miR-132, miR-26a, let-7b, and miR-145 could be considered as potential candidates as novel biomarkers in serous ovarian cancer" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/21345725", "http://www.ncbi.nlm.nih.gov/pubmed/22246341", "http://www.ncbi.nlm.nih.gov/pubmed/23888941", "http://www.ncbi.nlm.nih.gov/pubmed/23836287", "http://www.ncbi.nlm.nih.gov/pubmed/23542579", "http://www.ncbi.nlm.nih.gov/pubmed/23978303", "http://www.ncbi.nlm.nih.gov/pubmed/20035894", "http://www.ncbi.nlm.nih.gov/pubmed/19074899", "http://www.ncbi.nlm.nih.gov/pubmed/21571355", "http://www.ncbi.nlm.nih.gov/pubmed/18954897", "http://www.ncbi.nlm.nih.gov/pubmed/23918241", "http://www.ncbi.nlm.nih.gov/pubmed/21971665", "http://www.ncbi.nlm.nih.gov/pubmed/23272653", "http://www.ncbi.nlm.nih.gov/pubmed/23621186" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D035683", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D015415", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D010051", "http://www.disease-ontology.org/api/metadata/DOID:2394" ]

[ "Pyridostigmine and neostygmine are acetylcholinesterase inhibitors that are used as first-line therapy for symptomatic treatment of myasthenia gravis. Pyridostigmine is the most widely used acetylcholinesterase inhibitor. Extended release pyridotsygmine and novel acetylcholinesterase inhibitors inhibitors with oral antisense oligonucleotides are being studied." ]

[ "neostigmine", "pyridostigmine" ]

[ "Pyridostigmine is the most widely used acetylcholinesterase inhibitor.", "For more than 50 years the acetylcholinesterase inhibitor pyridostigmine bromide has been the drug of choice in the symptomatic therapy for myasthenia gravis. ", "The switch to SR-Pyr ameliorated the total quantified myasthenia gravis (QMG) score from 0.9 ± 0.5 to 0.6 ± 0.4 (p<0.001) in all patients and in the younger subgroup. This was accompanied by a significant improvement in the quality of life parameters. The health status valued by EuroQoL questionnaire improved from 0.626 ± 0.286 to 0.782 ± 0.186 (p<0.001). ", "Our results support the usefulness of SR-Pyr in an individualized therapeutic regimen to improve quality of life regardless of the patient's age in myasthenia gravis.", "This review focuses on treatment of MG, mainly on the use of the AChE inhibitor pyridostigmine.", "Despite a lack of data from well controlled clinical trials to support their use, AChE inhibitors, of which pyridostigmine is the most commonly used, are recommended as first-line therapy for MG. ", "Novel AChE inhibitors with oral antisense oligonucleotides have been developed and preliminary results appear to be promising.", "Except for one small and inconclusive trial of intranasal neostigmine, no randomised controlled trial has been conducted on the use of acetylcholinesterase inhibitors in myasthenia gravis. Response to acetylcholinesterase inhibitors in observational studies is so clear that a randomised controlled trial depriving participants in the placebo arm of treatment would be difficult to justify.", " Current guidelines and recommendations for MG treatment are based largely on clinical experience, retrospective analyses and expert consensus. Available therapies include oral acetylcholinesterase (AChE) inhibitors for symptomatic treatment, and short- and long-term disease-modifying treatments.", "Pyridostigmine has been used as a treatment for MG for over 50 years and is generally considered safe. It is suitable as a long-term treatment in patients with generalized non-progressive milder disease, and as an adjunctive therapy in patients with severe disease who are also receiving immunotherapy. ", "Acetylcholinesterase inhibitors provide temporary, symptomatic treatment for all forms of myasthenia gravis. " ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/21815707", "http://www.ncbi.nlm.nih.gov/pubmed/21845054", "http://www.ncbi.nlm.nih.gov/pubmed/21328290", "http://www.ncbi.nlm.nih.gov/pubmed/20663605", "http://www.ncbi.nlm.nih.gov/pubmed/21133188", "http://www.ncbi.nlm.nih.gov/pubmed/15610702" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D000110", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009157", "http://www.disease-ontology.org/api/metadata/DOID:437", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D002800", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004791" ]

[ "Yes, Denosumab was approved by the FDA in 2010." ]

[ "yes" ]

[ "Denosumab is a RANK-ligand antibody that was approved by the FDA in 2010 for the prevention of skeletal fractures in patients with bone metastases from solid tumors.", " The authors present the imaging findings and technical report of an attempted percutaneous vertebroplasty in the only patient found to be actively under treatment with denosumab after a retrospective review of the databank of patients with pathological fractures referred to the Department Radiology of the Ohio State University for percutaneous vertebroplasty (a total sample of 20 patients) since the FDA approval of denosumab (November 2010) until June of 2013 (a 30-month period).", "On the basis of this data, the FDA approved denosumab for the treatment of patients whose GCTB is unresectable, or when surgery is likely to result in severe morbidity.", "Denosumab (Prolia®) is a fully human monoclonal antibody for RANKL, which selectively inhibits osteoclastogenesis, being recently approved for the treatment of postmenopausal osteoporosis in women at a high or increased risk of fracture by the FDA in the United Sates and by the European Medicines Agency in Europe since June 2010.", "Recent phase II clinical trials with denosumab in skeletally mature adolescents over age 12 years and adults with GCTB, have shown both safety and efficacy, leading to its accelerated US FDA approval on 13 June 2013. ", "Zoledronic acid (ZA), an intravenously administered bisphosphonate, and Denosumab, a subcutaneously administered inhibitor of nuclear factor B ligand (RANKL), have already been approved by Food and Drug Administration (FDA) for their use in treatment of bone metastases.", "These results led to the approval of denosumab by the European Medicines Agency (EMA) and the US Food and Drug Administration (FDA), for the prevention of SREs in adults with bone metastases from solid tumors, including breast cancer.", "Alendronate, risedronate, zoledronic acid, denosumab, and teriparatide are Food and Drug Administration (FDA)-approved therapeutic options. ", "Several of these therapies have recently been approved by the FDA to treat bone cancer pain (bisphosphonates, denosumab) and others are currently being evaluated in human clinical trials (tanezumab).", "A fourth agent, denosumab (bone targeted therapy) was also recently approved by the FDA for patients with bone metastasis after showing a reduction in the occurrence of skeletal-related events. ", "AHRQ published an updated review in March 2012 that summarized the benefits and risks of osteoporosis medications in treatment and prevention of osteoporosis, including bisphosphonates (aledronate, risedronate, ibandronate, zoledronic acid), parathyroid hormone, teriparatide, calcitonin, estrogens (for prevention in postmenopausal women), selective estrogen receptor modulators (raloxifene), and denosumab(approved by the FDA in 2010). ", "Four new drugs have received U.S. Food and Drug Administration (FDA)-approval in 2010 and 2011: sipuleucel-T, an immunotherapeutic agent; cabazitaxel, a novel microtubule inhibitor; abiraterone acetate, a new androgen biosynthesis inhibitor; and denosumab, a bone-targeting agent. ", "Recently, the US FDA and the EMA approved denosumab (a fully human monoclonal antibody) to treat skeletal-related events in bone-metastatic prostate cancer.", "In addition to these new and emerging therapeutic agents, denosumab was approved for the prevention of skeletal complications in patients with bone metastases due to solid tumor malignancies, providing an alternative to zoledronic acid. ", "Recently, denosumab was FDA-approved for prevention of SREs in patients with bone metastases from solid tumors. ", "In the 2010s to date, an additional 3 antibodies (denosumab, belimumab, ipilimumab) have been approved and one antibody-drug conjugate (brentuximab vedotin) is undergoing regulatory review and may be approved in the US by August 30, 2011.", "We also review the evidence supporting the FDA's approval of denosumab (bone-targeted therapy) as a treatment option for men with CRPC and bony metastases. ", " It has been approved for clinical use by the FDA in the US and by the European Medicines Agency in Europe since June 2010 (trade name Prolia(™), Amgen, Thousand Oaks, CA, USA). ", "The fully human monoclonal antibody denosumab (Prolia(®)) has been recently approved by the European Medical Agency (EMEA) and the Food and Drug Administration (FDA) for the treatment of postmenopausal osteoporosis. ", "Raloxifene and denosumab are only FDA approved for postmenopausal osteoporosis.", "The new antiresorptive drug, denosumab, although FDA-approved only for postmenopausal women, has been shown in a study of men on ADT to increase bone density in spine, hip, and forearm and decrease vertebral fractures on x-ray. ", " Since then, an additional six human mAbs have received FDA approval: panitumumab, golimumab, canakinumab, ustekinumab, ofatumumab and denosumab. " ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/24126422", "http://www.ncbi.nlm.nih.gov/pubmed/22826702", "http://www.ncbi.nlm.nih.gov/pubmed/23759273", "http://www.ncbi.nlm.nih.gov/pubmed/21785279", "http://www.ncbi.nlm.nih.gov/pubmed/21113693", "http://www.ncbi.nlm.nih.gov/pubmed/21129866", "http://www.ncbi.nlm.nih.gov/pubmed/23956508", "http://www.ncbi.nlm.nih.gov/pubmed/22716221", "http://www.ncbi.nlm.nih.gov/pubmed/23757624", "http://www.ncbi.nlm.nih.gov/pubmed/23367751", "http://www.ncbi.nlm.nih.gov/pubmed/22074657", "http://www.ncbi.nlm.nih.gov/pubmed/21170699", "http://www.ncbi.nlm.nih.gov/pubmed/21942303", "http://www.ncbi.nlm.nih.gov/pubmed/24114694", "http://www.ncbi.nlm.nih.gov/pubmed/22540167", "http://www.ncbi.nlm.nih.gov/pubmed/24308016", "http://www.ncbi.nlm.nih.gov/pubmed/21208140", "http://www.ncbi.nlm.nih.gov/pubmed/23652187", "http://www.ncbi.nlm.nih.gov/pubmed/21470540", "http://www.ncbi.nlm.nih.gov/pubmed/24316116", "http://www.ncbi.nlm.nih.gov/pubmed/20811384" ]

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[ "http://www.biosemantics.org/jochem#4268082" ]

[ "DVL-1\nDVL-2\nDVL-3" ]

[ "DVL-1", "DVL-2", "DVL-3" ]

[ "Dishevelled (Dvl/Dsh) is a multi-module protein and a key regulator of both the canonical Wnt and the PCP pathway. In mouse, all Dvl1(-/-) ; Dvl2(-/-) double mutants display craniorachischisis, a severe form of open NTDs. ", " In this study, we explore the cause of HSCR by studying the expression of DVL-1 and DVL-3 genes and their proteins in the aganglionic segment and the ganglionic segment of colon in HSCR patients.", "Dishevelled (Dvl) proteins are key transducers of Wnt signaling encoded by members of a multi-gene family in vertebrates. We report here the divergent, tissue-specific expression patterns for all three Dvl genes in Xenopus embryos, which contrast dramatically with their expression patterns in mice.", "velopmental processes, including segmentation and neuroblast specification. We have isolated and characterized cDNA clones from two different human dsh-homologous genes, designated as DVL-1 and DVL-3. ", "In the Drosophila embryo dishevelled (dsh) function is required by target cells in order to respond to wingless (wg, the homolog of Wnt-1), demonstrating a role for dsh in Wnt signal transduction. We have isolated a mouse homolog of the Drosophila dsh segment polarity gene. The 695-amino-acid protein encoded by the mouse dishevelled gene (Dvl-1) shares 50% identity (65% similarity) with dsh.", "The Dvl-1 gene on chromosome 1p36 belongs to a family of highly conserved secreted proteins which regulates embryonic induction, generation of cell polarity and specification of cell fate through activation of Wnt signaling pathways. Wnt signaling activates the gene encoding DVL-1;", "We report here that the mouse Dishevelled-1 (Dvl-1) and Dishevelled-2 genes encode proteins that are differentially localized in Wnt-overexpressing PC12 cell lines (PC12/Wnt). ", "Recently, the DVL1 gene was identified as a middle molecule of the Wnt/beta-catenin signaling pathway. " ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/12883684", "http://www.ncbi.nlm.nih.gov/pubmed/24040443", "http://www.ncbi.nlm.nih.gov/pubmed/19618470", "http://www.ncbi.nlm.nih.gov/pubmed/8817329", "http://www.ncbi.nlm.nih.gov/pubmed/8856345", "http://www.ncbi.nlm.nih.gov/pubmed/23836490", "http://www.ncbi.nlm.nih.gov/pubmed/8149913", "http://www.ncbi.nlm.nih.gov/pubmed/7958461", "http://www.ncbi.nlm.nih.gov/pubmed/16457155" ]

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[ "Acrokeratosis paraneoplastic (Bazex syndrome) is a rare, but distinctive paraneoplastic dermatosis characterized by erythematosquamous lesions located at the acral sites and is most commonly associated with carcinomas of the upper aerodigestive tract." ]

[ "Bazex syndrome" ]

[ "Acrokeratosis paraneoplastica of Bazex is a rare but important paraneoplastic dermatosis, usually manifesting as psoriasiform rashes over the acral sites.", "[Paraneoplastic palmoplantar hyperkeratosis. Minor form of acrokeratosis neoplastica Bazex?].", "Acrokeratosis paraneoplastica Bazex is a rare, obligate paraneoplasia initially presenting with palmoplantar hyperkeratosis. ", "We diagnosed a minor form of acrokeratosis paraneoplastica Bazex. ", "Acrokeratosis paraneoplastica (Bazex syndrome): report of a case associated with small cell lung carcinoma and review of the literature.", "Acrokeratosis paraneoplastic (Bazex syndrome) is a rare, but distinctive paraneoplastic dermatosis characterized by erythematosquamous lesions located at the acral sites and is most commonly associated with carcinomas of the upper aerodigestive tract. ", "Bazex syndrome (acrokeratosis paraneoplastica): persistence of cutaneous lesions after successful treatment of an associated oropharyngeal neoplasm.", "Acrokeratosis paraneoplastica Bazex syndrome associated with esophageal squamocellular carcinoma.", "BACKGROUND: Acrokeratosis paraneoplastica Bazex (APB) is a very rare disease in the group of obligate paraneoplastic dermatoses, associated mostly with squamous cell carcinoma of the upper aerodigestive tract and metastatic cervical lymphadenopathy. ", "Acrokeratosis paraneoplastica (Bazex' syndrome).", "Acrokeratosis paraneoplastica (first described by Gougerot and Rupp in 1922) was named after Bazex who had then reported several cases in a French dermatological journal since 1965 (Bazex et al. in Bull Soc Fr Dermatol Syphiligr 72:182, 1965; Bazex and Griffiths in Br J Dermatol 102:301-306, 1980).METHOD: The study is a clinical case of a patient with acrokeratosis paraneoplastica.RESULTS: the patient was later diagnosed with a cervical lymph node metastasis and thereafter with a primary squamous cell carcinoma of the left upper lobe and upon treatment responded with the clearing of the skin changes.CONCLUSION: Identification of a paraneoplastic syndrome may enhance the earlier diagnosis of the associated tumor and may thus enable curative treatment.", "Acrokeratosis paraneoplastica (Bazex's syndrome): association with liposarcoma.", "Acrokeratosis paraneoplastica of Bazex as an indicator for underlying squamous cell carcinoma of the lung.", "Acrokeratosis paraneoplastica (Bazex syndrome) with oropharyngeal squamous cell carcinoma.", "Acrokeratosis paraneoplastica of Bazex: report of a case in a young black woman.", "Acrokeratosis paraneoplastica of Bazex.", "Acrokeratosis paraneoplastica (first described by Gougerot and Rupp in 1922) was named after Bazex who had then reported several cases in a French dermatological journal since 1965 (Bazex et al.", "Acrokeratosis paraneoplastica: Bazex syndrome.", "Bazex syndrome: acrokeratosis paraneoplastica.", "Acrokeratosis paraneoplastica (Bazex&apos; syndrome) is a rare but clinically distinctive dermatosis that has been associated in all reported cases, to our knowledge, with either a primary malignant neoplasm of the upper aerodigestive tract or metastatic cancer to the lymph nodes of the neck. Acrokeratosis paraneoplastica was found in a 53-year-old black man with squamous cell carcinoma of the tonsil.", "Bazex syndrome (acrokeratosis paraneoplastica) is a rare paraneoplastic syndrome that usually occurs in males over 40 years old and is particularly associated with squamous cell carcinoma of the upper aerodigestive tract and adenopathy above the diaphragm.The objectives of our article are (1) to describe a unique case of acrokeratosis paraneoplastica and (2) to review the current literature regarding skin findings, commonly associated neoplasms, and treatment options relative to this condition." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/3819049", "http://www.ncbi.nlm.nih.gov/pubmed/18775590", "http://www.ncbi.nlm.nih.gov/pubmed/22146896", "http://www.ncbi.nlm.nih.gov/pubmed/6225397", "http://www.ncbi.nlm.nih.gov/pubmed/18672707", "http://www.ncbi.nlm.nih.gov/pubmed/7796616", "http://www.ncbi.nlm.nih.gov/pubmed/16435144", "http://www.ncbi.nlm.nih.gov/pubmed/7640201", "http://www.ncbi.nlm.nih.gov/pubmed/22252191", "http://www.ncbi.nlm.nih.gov/pubmed/17097409", "http://www.ncbi.nlm.nih.gov/pubmed/17374318", "http://www.ncbi.nlm.nih.gov/pubmed/22470801", "http://www.ncbi.nlm.nih.gov/pubmed/8949310", "http://www.ncbi.nlm.nih.gov/pubmed/1521479", "http://www.ncbi.nlm.nih.gov/pubmed/1433123" ]

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[ "Antiarrhythmic drugs can be divided into four Vaughan Williams classes (I-IV). Class I antiarrhythmic agents have as a common action, blockade of the sodium channels. Class II agents are antisympathetic drugs, particularly the beta-adrenoceptor blockers. Class-III antiarrhythmics have as a common action the potassium-channel blockade. Class IV antiarrhythmic drugs are calcium channel blockers." ]

[ "Class I: sodium channel blockers", "ClassII: beta blockers", "Class III: potassium channel blockers", "Class IV: calcium channel blockers" ]

[ "Class II agents are antisympathetic drugs, particularly the beta-adrenoceptor blockers", "Class III antiarrhythmic agents include sotalol and amiodarone.", "Class IV antiarrhythmic drugs are the calcium channel blockers verapamil and diltiazem. ", "Other agents which do not fall neatly into the Vaughan Williams classification include digoxin and perhexiline.", "Antiarrhythmic drugs can be divided into four Vaughan Williams classes (I-IV) according to defined electrophysiological effects on the myocardium.", "Thus, the Vaughan Williams classification also coincides with the main myocardial targets of the antiarrhythmics, i.e., myocardial sodium-, potassium-, and calcium-channels or beta-adrenergic receptors. ", "The sodium-channel blockade induced by class-I substances is enhanced with increasing heart rates. Thus, class-I antiarrhythmics can be subclassified as substances showing a more exponential, an approximately linear, or rather saturated block-frequency relation.", "Class-III antiarrhythmics (potassium-channel blockade) can be further differentiated according to the component of the delayed rectifier potassium current (IK) which is inhibited by a drug. ", "Class-III substances inhibiting the slowly activating IKs component are currently under investigation and are expected to show a direct rate dependence.", "Antiarrhythmic agents are traditionally classified according to Vaughan Williams into four classes of action. Class I antiarrhythmic agents include most of the drugs traditionally thought of as antiarrhythmics, and have as a common action, blockade of the fast-inward sodium channel on myocardium. ", "Antiarrhythmic drugs can be divided into four Vaughan Williams classes (I-IV) according to defined electrophysiological effects on the myocardium", "The classification of antiarrhythmic agents according to Vaughan Williams is based on electrophysiological findings in isolated heart muscle and defines four classes of drug actions.", "Antiarrhythmic agents are traditionally classified according to Vaughan Williams into four classes of action. Class I antiarrhythmic agents include most of the drugs traditionally thought of as antiarrhythmics, and have as a common action, blockade of the fast-inward sodium channel on myocardium.", "Class II agents are antisympathetic drugs, particularly the b-adrenoceptor blockers.", "Class III antiarrhythmic agents include sotalol and amiodarone. ", "Class IV antiarrhythmic drugs are the calcium channel blockers verapamil and diltiazem. ", "These are classified according to their electrophysiological effects observed in isolated cardiac tissues in vitro (Vaughan Williams, 1989). Fast sodium channel blockers (class I) which reduce the upstroke velocity of the action potential are usually subclassified into three groups, class I A-C, according to their effect on the action potential duration. Beta-adrenergic antagonists (class II) exert their effects by antagonizing the electrophysiological effects of beta-adrenergic catecholamines. Class III antiarrhythmic agents (eg amiodarone) prolong the action potential and slow calcium channel blockers (class IV) suppress the calcium inward current and calcium-dependent action potentials. " ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/9803978", "http://www.ncbi.nlm.nih.gov/pubmed/11564050", "http://www.ncbi.nlm.nih.gov/pubmed/1290288", "http://www.ncbi.nlm.nih.gov/pubmed/7875632", "http://www.ncbi.nlm.nih.gov/pubmed/10810787" ]

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[ "Notch signaling is an evolutionarily conserved mechanism, used to regulate cell fate decisions. Four Notch receptors have been identified in man: Notch-1, Notch-2, Notch-3 and Notch-4." ]

[ "Notch-1", "Notch-2", "Notch-3", "Notch-4" ]

[ "Here, we investigate protein interactions between NOTCH3 and other vascular Notch isoforms and characterize the effects of elevated NOTCH3 on smooth muscle gene regulation. We demonstrate that NOTCH3 forms heterodimers with NOTCH1, NOTCH3, and NOTCH4.", "We conclude that CADASIL mutants of NOTCH3 complex with NOTCH1, 3, and 4, slow NOTCH3 clearance, and that overexpressed wild type and mutant NOTCH3 protein interfere with key NOTCH-mediated functions in smooth muscle cells.", "In the vertebrate embryo, skeletal muscle is derived from the myotome of the somites. Notch1-3 demonstrate overlapping and distinct expression patterns in mouse somites. Notch1 and Notch2 have been shown to be inhibitors of skeletal myogenesis. ", "In this study, we analyzed the immunohistochemical staining pattern of four Notch receptors (Notch1-4) and their ligands (Delta1 and Jagged1) in 14 synovial tissues obtained from 14 RA patients. ", "Notch signaling is an evolutionarily conserved mechanism, used to regulate cell fate decisions. Four Notch receptors have been identified in man (Notch-1 to -4).", "All 4 receptors were expressed in the adult liver, with no significant differences in the levels of Notch-1, -2, and -4 messenger RNA (mRNA) between normal and diseased liver. However, Notch-3 expression appeared to be increased in diseased tissue. ", "We studied the immunohistochemical expression of NOTCH2 and its isoforms NOTCH1, NOTCH3, and NOTCH4 and the NOTCH2 primary ligand JAGGED1 in hepatoblastomas.", "There are four different mammalian Notch receptors that can be activated by five cell surface ligands", "There are four mammalian Notch receptors that have only partially overlapping functions despite sharing similar structures and ligands." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/23028706", "http://www.ncbi.nlm.nih.gov/pubmed/21639801", "http://www.ncbi.nlm.nih.gov/pubmed/11532344", "http://www.ncbi.nlm.nih.gov/pubmed/22842086", "http://www.ncbi.nlm.nih.gov/pubmed/21356309", "http://www.ncbi.nlm.nih.gov/pubmed/11732008", "http://www.ncbi.nlm.nih.gov/pubmed/16307184" ]

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[ "The defining characteristics of cellular senescence are altered morphology, arrested cell-cycle progression, development of aberrant gene expression with proinflammatory behavior, and telomere shortening." ]

[ "altered morphology", "arrested cell-cycle progression", "development of aberrant gene expression with proinflammatory behavior", "telomere shortening" ]

[ "Cellular senescence is recognized as a critical cellular response to prolonged rounds of replication and environmental stresses. Its defining characteristics are arrested cell-cycle progression and the development of aberrant gene expression with proinflammatory behavior.", "telomeres are the central timing mechanism for cellular aging", "Recent research has shown that inserting a gene for the protein component of telomerase into senescent human cells reextends their telomeres to lengths typical of young cells, and the cells then display all the other identifiable characteristics of young, healthy cells.", "Our data demonstrate that Sod1 transfected cell lines that have an elevation in the ratio of Sod1 activity to Gpx1 activity produce higher levels of H2O2 and exhibit well characterised markers of cellular senescence viz. slower proliferation and altered morphology." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/9624027", "http://www.ncbi.nlm.nih.gov/pubmed/18976161", "http://www.ncbi.nlm.nih.gov/pubmed/8824885" ]

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[ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0090398", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016922", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:2000772", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:2000773", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:2000774" ]

[ "Orteronel was developed for treatment of castration-resistant prostate cancer." ]

[ "castration-resistant prostate cancer" ]

[ "Pooled-analysis was also performed, to assess the effectiveness of agents targeting the androgen axis via identical mechanisms of action (abiraterone acetate, orteronel).", "The experimental interventions tested in these studies were enzalutamide, ipilimumab, abiraterone acetate, orteronel and cabazitaxel. ", " Pooled analysis of androgen synthesis inhibitors orteronel and abiraterone resulted in significantly increased overall and progression-free survival for anti-androgen agents, compared to placebo (hazard ratio for death: 0.76, 95% CI 0.67 to 0.87, P<0.0001; hazard ratio for radiographic progression: 0.7, 95% CI 0.63 to 0.77, P<0.00001). ", "Agents targeting the androgen axis (enzalutamide, abiraterone, orteronel) significantly prolonged rPFS, compared to placebo. ", "Orteronel plus prednisone in patients with chemotherapy-naive metastatic castration-resistant prostate cancer (ELM-PC 4): a double-blind, multicentre, phase 3, randomised, placebo-controlled trial.", "BACKGROUND: Orteronel is an investigational, partially selective inhibitor of CYP 17,20-lyase in the androgen signalling pathway, a validated therapeutic target for metastatic castration-resistant prostate cancer. We assessed orteronel in chemotherapy-naive patients with metastatic castration-resistant prostate cancer.", "NTERPRETATION: In chemotherapy-naive patients with metastatic castration-resistant prostate cancer, radiographic progression-free survival was prolonged with orteronel plus prednisone versus placebo plus prednisone.", "On the basis of these and other data, orteronel is not undergoing further development in metastatic castration-resistant prostate cancer.", "Phase III, randomized, double-blind, multicenter trial comparing orteronel (TAK-700) plus prednisone with placebo plus prednisone in patients with metastatic castration-resistant prostate cancer that has progressed during or after docetaxel-based therapy: ELM-PC 5.", "This study examined orteronel in patients with metastatic castration-resistant prostate cancer that progressed after docetaxel therapy.", "Longer rPFS and a higher PSA50 rate with orteronel-prednisone indicate antitumor activity.", "A phase 1 multiple-dose study of orteronel in Japanese patients with castration-resistant prostate cancer.", "We evaluated the safety, tolerability, pharmacokinetics, pharmacodynamics, and antitumor effect of orteronel with or without prednisolone in Japanese patients with castration-resistant prostate cancer (CRPC).", "CONCLUSIONS: Orteronel at doses up to 400 mg BID was tolerable in Japanese CRPC patients.", "Orteronel for the treatment of prostate cancer.", "Orteronel (also known as TAK-700) is a novel hormonal therapy that is currently in testing for the treatment of prostate cancer.", "Orteronel is a nonsteroidal, selective inhibitor of 17,20-lyase that was recently in phase 3 clinical development as a treatment for castration-resistant prostate cancer.", "Early reports of clinical studies demonstrate that orteronel treatment leads to reduced prostate-specific antigen levels, a marker of prostate cancer tumor burden, and more complete suppression of androgen synthesis than conventional androgen deprivation therapies that act in the testes alone.", "Discovery of orteronel (TAK-700), a naphthylmethylimidazole derivative, as a highly selective 17,20-lyase inhibitor with potential utility in the treatment of prostate cancer.", "Therefore, (+)-3c (termed orteronel [TAK-700]) was selected as a candidate for clinical evaluation and is currently in phase III clinical trials for the treatment of castration-resistant prostate cancer.", "We assessed orteronel in chemotherapy-naive patients with metastatic castration-resistant prostate cancer.", "Orteronel is a nonsteroidal, selective inhibitor of 17,20-lyase that was recently in phase 3 clinical development as a treatment for castration-resistant prostate cancer. ", "Phase I/II trial of orteronel (TAK-700)--an investigational 17,20-lyase inhibitor--in patients with metastatic castration-resistant prostate cancer.", "On the basis of these and other data, orteronel is not undergoing further development in metastatic castration-resistant prostate cancer.FUNDING: Millennium Pharmaceuticals, Inc, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited.", "New androgen biosynthesis inhibitors have been developed, such as orteronel (TAK-700), but also new antiandrogens (enzalutamide, ARN-509, ODM-201) or even agents with a dual mechanism of action (galeterone). In this review the development of new hormonal therapies following the arrival of abiraterone for the treatment of prostate cancer will be summarized." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/24799061", "http://www.ncbi.nlm.nih.gov/pubmed/24418642", "http://www.ncbi.nlm.nih.gov/pubmed/25537627", "http://www.ncbi.nlm.nih.gov/pubmed/25701170", "http://www.ncbi.nlm.nih.gov/pubmed/25624429", "http://www.ncbi.nlm.nih.gov/pubmed/25264242", "http://www.ncbi.nlm.nih.gov/pubmed/21978946", "http://www.ncbi.nlm.nih.gov/pubmed/26150028", "http://www.ncbi.nlm.nih.gov/pubmed/24100689" ]

[]

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

[ "Although is still controversial, Trastuzumab (Herceptin) can be of potential use in the treatment of prostate cancer overexpressing HER2, either alone or in combination with other drugs." ]

[ "yes" ]

[ "Herceptin is widely used in treating Her2-overexpressing breast cancer. However, the application of Herceptin in prostate cancer is still controversial.", "Our data demonstrate that Re-188-labeled Herceptin effectively inhibited the growth of DU145 cells compared to the Herceptin- and Re-188-treated cohorts. This implies that targeting Her2 by both radio- and immuno- therapy might be a potential strategy for treating patients with androgen-independent prostate cancer.", "epidermal growth factor receptor (EGFR) family members are potential targets for therapy using extra-cellular domain receptor binding agents, such as the antibodies trastuzumab and cetuximab", " there were tendencies for upregulation of HER2, increased co-expression of EGFR and HER2 and downregulation of HER3 in the prostate cancer lymph node metastases in comparison to the primary tumors. ", "We performed a comparative analysis in vitro and in vivo of the antitumor effects of three different antibodies targeting different epitopes of ErbB2: Herceptin (trastuzumab), 2C4 (pertuzumab) and Erb-hcAb (human anti-ErbB2-compact antibody), a novel fully human compact antibody produced in our laboratory. Herein, we demonstrate that the growth of both androgen-dependent and independent prostate cancer cells was efficiently inhibited by Erb-hcAb. The antitumor effects induced by Erb-hcAb on some cell lines were more potent than those observed for either Herceptin or 2C4.", "These findings suggest that a systemic delivery of 212Pb-trastuzumab could be an effective modality for management of advanced human prostate cancer.", "Human epidermal growth factor receptor type 2 (HER2) overexpression supports proliferation of androgen-independent prostate cancer (PC)", "Radiolabeled ABY-025 Affibody molecule provides higher contrast in imaging of HER2-expressing PC xenografts than radiolabeled trastuzumab. ", "These studies indicate that dual EGFR/HER2 inhibition, administered together with AWT, sensitize prostate cancer cells to apoptosis during AWT", "The overall goal of these studies is to determine whether dual inhibition of the receptor tyrosine kinases epidermal growth factor receptor (EGFR) and HER2 would prolong the effectiveness of this treatment in prostate cancer. ", "The expression of HER2 was demonstrated and quantified in all three tested prostate cancer cell-lines.", "Such features would definitely favor the use of radiometal labels for trastuzumab and, most likely, for affibody molecules", "our data demonstrate that Her2 plays an important role in the support of AR protein stability in the transition of androgen requirement in prostate cancer cells. We hope these findings will provide novel insight into the treatment of hormone-refractory prostate cancer.", "These two cell lines exhibited distinct responses to Her2 activation (by heregulin treatment) on Her2 phosphorylation and Her2 inhibition (by AG825 or Herceptin treatments) on proliferation", " While prostate cancers that express high levels of HER-2 are resistant to the killing effects of trastuzumab, they can be targeted for selective gene expression and destruction by lentiviruses with envelope proteins engineered to bind to this therapeutic antibody", "Overexpression of ErbB-2 and EGFR has been associated with aggressive disease and poor patient prognosis in a range of human tumour types (e.g. breast, lung, ovarian, prostate", "Various approaches have been developed to target the ErbB signalling pathways including monoclonal antibodies (trastuzumab/Herceptin", "The data from these in vitro and in vivo studies supported advancement of radiolabeled trastuzumab into two clinical studies", "Tumor targeting was evaluated in mice bearing subcutaneous (s.c.) xenografts of colorectal, pancreatic, ovarian, and prostate carcinomas.", "we found that although prostate cancers that express high levels of HER-2 are resistant to the killing effects of trastuzumab, they can be targeted for selective gene expression and destruction by viruses with envelope proteins engineered to bind this antibody", "detection of prostate cancer (PCa) and advances in hormonal and chemotherapy treatments have provided great clinical benefits to patients with early stages of the disease.", "MAbs directed to established targets include those approved for other solid tumors, including anti-human epidermal growth factor receptor-2 (HER2) MAb trastuzumab", "We conclude that Her2/neu expression in the peripheral blood mononuclear cell fraction of prostate cancer patients is frequent and therefore this assay may potentially be useful to detect the presence of micrometastatic disease in men with prostate cancer and for monitoring patients enrolled in trastuzumab-based therapeutic protocols.", "This study suggests that the docetaxel/trastuzumab combination may prove an effective therapeutic approach for HER2-expressing hormone-refractory prostate cancer.", "there was no significant difference in antimetastatic activity between the emulsion and the immunoemulsion despite the affinity of the immunoemulsion towards the HER2 receptor. ", "a targeted drug delivery system based on cationic emulsion covalently linked to anti-HER2 monoclonal antibody (Herceptin), in a well-established in vivo pharmacologic model of metastatic prostate cancer that overexpresses the HER2 receptor", "The finding of strong, consistent HER-2/neu expression in ACBCC suggests that treatment with Herceptin (trastuzumab) may be effective in patients with this rare tumour.", "Although HER2 can be over-expressed in prostate cancer, there is no clinical data to support the use of trastuzumab for prostate cancer patients.", "whereas the effect of the trastuzumab-RT combination was inferior to that predicted by the individual effects.", "HER 1-2 targeting of hormone-refractory prostate cancer by ZD1839 and trastuzumab", "Trastuzumab (Herceptin) as a single agent demonstrated poor efficacy in treating HRPC.", "To investigate the efficacy and toxicity of the antibody to the HER-2/neu receptor (trastuzumab, Herceptin) in the treatment of advanced hormone-refractory prostate cancer (HRPC)", "Conclusions regarding the predictive value of HER-2 status on outcome after trastuzumab-based therapy were not reached and were only drawn after larger-scale screening efforts. ", "rastuzumab plus docetaxel in HER-2/neu-positive prostate carcinoma", "clinical trials are currently in progress in patients with prostate cancer testing novel agents that selectively interfere with these receptors, such as trastuzumab,", "ytotoxicity of human prostate cancer cell lines in vitro and induction of apoptosis using 213Bi-Herceptin alpha-conjugate", "The clinical interpretation of c-erbB-2 abnormalities should reflect the complexity of c-erbB-2 mediated regulatory pathway and explain why tumours with overexpression/amplification of c-erbB-2 very often do not respond to therapy using Herceptin", "HER-2 overexpression also has been reported in up to 60% of patients with hormone-refractory prostate carcinoma (HRPC) and was correlated with shortened survival", "Unlike breast carcinoma and contrary to prior reports, HER-2 overexpression by IHC in archival prostate tissue from patients who eventually developed hormone-refractory disease was infrequent. There did not appear to be any correlation between HER-2 overexpression by IHC and shed HER-2 antigen levels in serum by ELISA in this tumor type.", "Further development of trastuzumab for the treatment of patients with metastatic prostate carcinoma is not feasible until more reliable and practical methods of sampling metastatic disease are developed to identify patients with HER-2 positive tumors.", "the expression of ERBB2 in prostate cancer is relatively low, and is not altered during disease progression. Thus, it is unlikely that treatment modalities relying on the overexpression of ERBB2 gene will be useful in treating prostate cancer.", "A phase I study was designed to evaluate docetaxel/estramustine plus trastuzumab, a humanized monoclonal antibody that binds to the HER2 receptor, in patients with metastatic androgen-independent prostate cancer (AIPC)", "Laboratory evidence also supports the clinical evaluation of docetaxel-based combinations that include agents such as trastuzumab and/or estramustine", "trastuzumab, a monoclonal antibody binding to the HER2 receptor; immunotoxin conjugates use an antibody directed against EGFR joined to a cell toxin. All are in clinical trials for a number of cancers, including prostate cancer", "we investigated the antitumor efficacy of Herceptin, a new recombinant humanized anti-HER2/neu antibody, which exhibits cytostatic activity on breast and prostate cancer cells that overexpress the HER2 oncogene.", "trastuzumab was found to have additive and synergistic effects with some chemotherapeutic agents", "ER-2/neu as a therapeutic target in non-small cell lung cancer, prostate cancer", "in these prostate cancer model systems, Herceptin alone has clinical activity only in the androgen-dependent tumor and has at least an additive effect on growth,", "anti-HER2 receptor monoclonal antibody Herceptin significantly enhanced growth inhibition of the MDA PCa 2a cells." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/23294030", "http://www.ncbi.nlm.nih.gov/pubmed/10473102", "http://www.ncbi.nlm.nih.gov/pubmed/11786427", "http://www.ncbi.nlm.nih.gov/pubmed/17210707", "http://www.ncbi.nlm.nih.gov/pubmed/21364123", "http://www.ncbi.nlm.nih.gov/pubmed/12173324", "http://www.ncbi.nlm.nih.gov/pubmed/22322558", "http://www.ncbi.nlm.nih.gov/pubmed/16163160", "http://www.ncbi.nlm.nih.gov/pubmed/11236029", "http://www.ncbi.nlm.nih.gov/pubmed/10519379", "http://www.ncbi.nlm.nih.gov/pubmed/15264245", "http://www.ncbi.nlm.nih.gov/pubmed/20716957", "http://www.ncbi.nlm.nih.gov/pubmed/11502465", "http://www.ncbi.nlm.nih.gov/pubmed/15046685", "http://www.ncbi.nlm.nih.gov/pubmed/17211467", "http://www.ncbi.nlm.nih.gov/pubmed/11920466", "http://www.ncbi.nlm.nih.gov/pubmed/17142577", "http://www.ncbi.nlm.nih.gov/pubmed/11685722", "http://www.ncbi.nlm.nih.gov/pubmed/21844010", "http://www.ncbi.nlm.nih.gov/pubmed/18038879", "http://www.ncbi.nlm.nih.gov/pubmed/12677892", "http://www.ncbi.nlm.nih.gov/pubmed/15036648", "http://www.ncbi.nlm.nih.gov/pubmed/15571968", "http://www.ncbi.nlm.nih.gov/pubmed/22977535", "http://www.ncbi.nlm.nih.gov/pubmed/23255921", "http://www.ncbi.nlm.nih.gov/pubmed/15919200", "http://www.ncbi.nlm.nih.gov/pubmed/15139054", "http://www.ncbi.nlm.nih.gov/pubmed/18071949", "http://www.ncbi.nlm.nih.gov/pubmed/19373278", "http://www.ncbi.nlm.nih.gov/pubmed/11331475", "http://www.ncbi.nlm.nih.gov/pubmed/22137850", "http://www.ncbi.nlm.nih.gov/pubmed/22505344", "http://www.ncbi.nlm.nih.gov/pubmed/21326934", "http://www.ncbi.nlm.nih.gov/pubmed/21254978", "http://www.ncbi.nlm.nih.gov/pubmed/11685733" ]

[]

[ "http://www.biosemantics.org/jochem#4002084", "http://www.disease-ontology.org/api/metadata/DOID:10283" ]

[ "The GLT8D1 gene codes for the protein named glycosyltransferase 8 domain containing 1" ]

[ "glycosyltransferase 8 domain containing 1" ]

[]

[ "http://www.ncbi.nlm.nih.gov/pubmed/24114764", "http://www.ncbi.nlm.nih.gov/pubmed/24373612" ]

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[ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0016757", "http://www.uniprot.org/uniprot/GL8D1_DANRE", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016695", "http://www.uniprot.org/uniprot/GL8D1_BOVIN" ]

[ "The Yamanaka factors are the OCT4, SOX2, MYC, and KLF4 transcription factors" ]

[ "OCT4", "Oct3/4", "Pou5f1", "SOX2", "MYC", "c-MYC", "KLF4" ]

[ "Yamanaka factors (OCT4, SOX2, MYC, and KLF4", "Yamanaka factors' (Oct4, Sox2, Klf4 and c-Myc)", "Yamanaka factors (Oct4, Sox2, Klf4, and c-Myc) ", "Yamanaka factors (c-myc, KLF4, Oct3/4 and SOX2)", "Yamanaka factors (i.e., Oct4, Sox2, Klf4, and c-Myc) ", "Yamanaka factors (Oct3/4, Sox2, Klf4, and c-Myc)", "Yamanaka factors (OCT4, SOX2, KLF4, cMYC - OSKM", "Oct4, Sox2, Klf4 and cMyc (4TF, Yamanaka factors) ", "Yamanaka factors (Pou5f1, Myc, Klf4, and Sox2) ", "c-Myc, Klf4, Oct3/4, and Sox2 (the so-called \"Yamanaka factors\")", "Yamanaka factors, Oct3/4, Sox2, Klf4, and c-Myc", "Yamanaka factors, namely Sox2, Oct3/4 (Pou5f1), Klf4, and c-Myc", "Oct4, Sox2, Klf4 and c-Myc, also known as the Yamanaka factors. ", "Yamanaka factors (SOX2, OCT3/4, and KLF4, with or without c-MYC)", "Yamanaka factors Oct4, Sox2, Klf4, and c-Myc", "amanaka factors (Oct3/4, Sox2, Klf4, c-Myc)", "Yamanaka factors (Oct3/4, Sox2, Klf4, c-Myc) are highly expressed in embryonic stem (ES) cells, and their over-expression can induce pluripotency in both mouse and human somatic cells, indicating that these factors regulate the developmental signaling network necessary for ES cell pluripotency.", "These protein sets have been called the Yamanaka factors, namely Sox2, Oct3/4 (Pou5f1), Klf4, and c-Myc, and the Thomson factors, namely Sox2, Oct3, Lin28, and Nanog", "Yamanaka factors (Oct3/4, Sox2, Klf4, c-Myc) are highly expressed in embryonic stem (ES) cells, and their over-expression can induce pluripotency in both mouse and human somatic cells, indicating that these factors regulate the developmental signaling network necessary for ES cell pluripotency", "Transcription factors, Oct4, Sox2, Klf4 and cMyc (4TF, Yamanaka factors) are used as basal conditions to generate iPS cells", "Generation of induced pluripotent stem (iPS) cells from somatic cells has been successfully achieved by ectopic expression of four transcription factors, Oct4, Sox2, Klf4 and c-Myc, also known as the Yamanaka factors" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/23658991", "http://www.ncbi.nlm.nih.gov/pubmed/21839145", "http://www.ncbi.nlm.nih.gov/pubmed/23612755", "http://www.ncbi.nlm.nih.gov/pubmed/21761058", "http://www.ncbi.nlm.nih.gov/pubmed/23939864", "http://www.ncbi.nlm.nih.gov/pubmed/24150221", "http://www.ncbi.nlm.nih.gov/pubmed/22357549", "http://www.ncbi.nlm.nih.gov/pubmed/20144262", "http://www.ncbi.nlm.nih.gov/pubmed/23527808", "http://www.ncbi.nlm.nih.gov/pubmed/21640101", "http://www.ncbi.nlm.nih.gov/pubmed/19030024", "http://www.ncbi.nlm.nih.gov/pubmed/23704989", "http://www.ncbi.nlm.nih.gov/pubmed/22449255", "http://www.ncbi.nlm.nih.gov/pubmed/22075965", "http://www.ncbi.nlm.nih.gov/pubmed/21249204", "http://www.ncbi.nlm.nih.gov/pubmed/23166588" ]

[]

[]

[ "The chromosome-centric human proteome project aims to systematically map all human proteins, chromosome by chromosome, in a gene-centric manner through dedicated efforts from national and international teams", "The Chromosome-Centric Human Proteome Project (C-HPP) is an international effort for creating an annotated proteomic catalog for each chromosome. (PMID: 23312004) The chromosome-centric human proteome project aims to systematically map all human proteins, chromosome by chromosome, in a gene-centric manner through dedicated efforts from national and international teams. (PMID: 23308364) The Chromosome-centric Human Proteome Project (C-HPP) aims to systematically map the entire human proteome with the intent to enhance our understanding of human biology at the cellular level. (PMID: 23253012)" ]

[]

[ "The Chromosome-Centric Human Proteome Project (C-HPP) is an international effort for creating an annotated proteomic catalog for each chromosome", "The chromosome-centric human proteome project aims to systematically map all human proteins, chromosome by chromosome, in a gene-centric manner through dedicated efforts from national and international teams", "A gene-centric Human Proteome Project has been proposed to characterize the human protein-coding genes in a chromosome-centered manner to understand human biology and disease.", "dedicated to a systematic description of proteins as gene products encoded in the human genome (the C-HPP)", "a chromosome-centric protein mapping strategy, termed C-HPP", "The Chromosome-centric Human Proteome Project (C-HPP) aims to systematically map the entire human proteome with the intent to enhance our understanding of human biology at the cellular level.", "The objective of the international Chromosome-Centric Human Proteome Project (C-HPP) is to map and annotate all proteins encoded by the genes on each human chromosome. The C-HPP consortium was established to organize a collaborative network among the research teams responsible for protein mapping of individual chromosomes and to identify compelling biological and genetic mechanisms influencing colocated genes and their protein products. The C-HPP aims to foster the development of proteome analysis and integration of the findings from related molecular -omics technology platforms through collaborations among universities, industries, and private research groups.", "The goal of the Human Proteome Project (HPP) is to fully characterize the 21,000 human protein-coding genes with respect to the estimated two million proteins they encode. As such, the HPP aims to create a comprehensive, detailed resource to help elucidate protein functions and to advance medical treatment.", "The Chromosome-centric Human Proteome Project (C-HPP) aims to define all proteins encoded in each chromosome and especially to identify proteins that currently lack evidence by mass spectrometry.", "Our results will contribute to the accomplishment of the primary goal of the C-HPP in identifying so-called \"missing proteins\" and generating a whole protein catalog for each chromosome.", "there is only little information relative to their abundance, distribution, subcellular localization, interactions, or cellular functions. The aim of the HUPO Human Proteome Project (HPP, www.thehpp.org ) is to collect this information for every human protein.", ". To support the efforts of the Chromosome-centric Human Proteome Project Consortium, we have annotated these proteins with their respective chromosome location.", "One of the major challenges of a chromosome-centric proteome project is to explore in a systematic manner the potential proteins identified from the chromosomal genome sequence, but not yet characterized on a protein level.", "The Chromosome 16 Consortium forms part of the Human Proteome Project that aims to develop an entire map of the proteins encoded by the human genome following a chromosome-centric strategy (C-HPP) to make progress in the understanding of human biology in health and disease (B/D-HPP).", "A first research development progress report of the Chromosome 19 Consortium with members from Sweden, Norway, Spain, United States, China and India, a part of the Chromosome-centric Human Proteome Project (C-HPP) global initiative, is presented ( http://www.c-hpp.org ).", "In an effort to map the human proteome, the Chromosome-centric Human Proteome Project (C-HPP) was recently initiated." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/23312004", "http://www.ncbi.nlm.nih.gov/pubmed/23253012", "http://www.ncbi.nlm.nih.gov/pubmed/23252913", "http://www.ncbi.nlm.nih.gov/pubmed/22966780", "http://www.ncbi.nlm.nih.gov/pubmed/23249167", "http://www.ncbi.nlm.nih.gov/pubmed/23259496", "http://www.ncbi.nlm.nih.gov/pubmed/21742803", "http://www.ncbi.nlm.nih.gov/pubmed/23205526", "http://www.ncbi.nlm.nih.gov/pubmed/23234512", "http://www.ncbi.nlm.nih.gov/pubmed/23308364", "http://www.ncbi.nlm.nih.gov/pubmed/23214983", "http://www.ncbi.nlm.nih.gov/pubmed/23276153", "http://www.ncbi.nlm.nih.gov/pubmed/23153008", "http://www.ncbi.nlm.nih.gov/pubmed/23227862", "http://www.ncbi.nlm.nih.gov/pubmed/22443261" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D006801", "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=D002875", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D002877", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D041322" ]

[ "The protein Pannexin1 is localized to the plasma membranes." ]

[ "plasma membrane" ]

[ "zfPanx1 was identified on the surface of horizontal cell dendrites invaginating deeply into the cone pedicle near the glutamate release sites of the cones, providing in vivo evidence for hemichannel formation at that location.", "pannexin1, a vertebrate homolog of invertebrate gap junction proteins.", "The specific profile of gap junction proteins, the connexins, expressed in these different cell types forms compartments of intercellular communication that can be further shaped by the release of extracellular nucleotides via pannexin1 channels. ", "Recent studies demonstrated that ATP can be released from cells in a controlled manner through pannexin (Panx) channels.", "The ATP release channel Pannexin1 (Panx1) is self-regulated", "The membrane protein Pannexin1 forms two open-channel conformations depending on the mode of activation.", " Pannexin1 channels traffic to the plasma membrane.", "We previously showed that pannexins form oligomeric channels but unlike connexins and innexins, they form only single membrane channels.", "ATP release channel Pannexin1 ", "Pannexin1 (Panx1) is a newly discovered extracellular ATP release channel with a wide tissue distribution and diverse biological functions in mammals.", "In mammals, a single pannexin1 gene (Panx1) is widely expressed in the CNS including the inner and outer retinae, forming large-pore voltage-gated membrane channels, which are involved in calcium and ATP signaling. ", "Six of them form a \"gap junction hemichannel-like\" structure that connects the cytoplasm with the extracellular space; here they will be called Panx1 channels. These are poorly selective channels permeable to ions, small metabolic substrate, and signaling molecules." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/24642372", "http://www.ncbi.nlm.nih.gov/pubmed/25056878", "http://www.ncbi.nlm.nih.gov/pubmed/24694658", "http://www.ncbi.nlm.nih.gov/pubmed/25698922", "http://www.ncbi.nlm.nih.gov/pubmed/17064878", "http://www.ncbi.nlm.nih.gov/pubmed/24782784", "http://www.ncbi.nlm.nih.gov/pubmed/26100513", "http://www.ncbi.nlm.nih.gov/pubmed/25007779", "http://www.ncbi.nlm.nih.gov/pubmed/19409451", "http://www.ncbi.nlm.nih.gov/pubmed/24194896" ]

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[ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0051179" ]

[ "Mutations in the POLG gene have emerged as one of the most common causes of inherited mitochondrial disease in children and adults. They are responsible for a heterogeneous group of at least 6 major phenotypes of neurodegenerative disease that include: 1) childhood Myocerebrohepatopathy Spectrum disorders (MCHS), 2) Alpers syndrome, 3) Ataxia Neuropathy Spectrum (ANS) disorders, 4) Myoclonus Epilepsy Myopathy Sensory Ataxia (MEMSA), 5) autosomal recessive Progressive External Ophthalmoplegia (arPEO), and 6) autosomal dominant Progressive External Ophthalmoplegia (adPEO).", "Mutations in the POLG gene have emerged as one of the most common causes of inherited mitochondrial disease in children and adults. They are responsible for a heterogeneous group of at least 6 major phenotypes of neurodegenerative disease that include: 1) childhood Myocerebrohepatopathy Spectrum disorders (MCHS), 2) Alpers syndrome, 3) Ataxia Neuropathy Spectrum (ANS) disorders, 4) Myoclonus Epilepsy Myopathy Sensory Ataxia (MEMSA), 5) autosomal recessive Progressive External Ophthalmoplegia (arPEO), and 6) autosomal dominant Progressive External Ophthalmoplegia (adPEO)" ]

[ "childhood Myocerebrohepatopathy Spectrum disorders (MCHS)", "Alpers syndrome", "Ataxia Neuropathy Spectrum (ANS) disorders", "Myoclonus Epilepsy Myopathy Sensory Ataxia (MEMSA)", "autosomal recessive Progressive External Ophthalmoplegia (arPEO)", "autosomal dominant Progressive External Ophthalmoplegia (adPEO)" ]

[ "Mutations in the POLG gene have emerged as one of the most common causes of inherited mitochondrial disease in children and adults. They are responsible for a heterogeneous group of at least 6 major phenotypes of neurodegenerative disease that include: 1) childhood Myocerebrohepatopathy Spectrum disorders (MCHS), 2) Alpers syndrome, 3) Ataxia Neuropathy Spectrum (ANS) disorders, 4) Myoclonus Epilepsy Myopathy Sensory Ataxia (MEMSA), 5) autosomal recessive Progressive External Ophthalmoplegia (arPEO), and 6) autosomal dominant Progressive External Ophthalmoplegia (adPEO)", "Mutations in the gene encoding mitochondrial DNA polymerase gamma (POLG), the enzyme that synthesises mitochondrial DNA (mtDNA), have been associated with a mitochondrial disease-autosomal dominant or recessive progressive external ophthalmoplegia-and multiple deletions of mtDNA.", "About 150 mutations in the human POLG have been identified in patients with mitochondrial diseases such as Alpers syndrome, progressive external ophthalmoplegia, and ataxia-neuropathy syndromes.", "Nineteen exhibited a cluster of three or more predefined clinical manifestations suggestive of POLG-related disease: progressive external ophthalmoplegia, seizures and/or an abnormal electroencephalogram, neuropathy, ataxia, liver function abnormalities, migraine or dysphagia/dysarthria. ", "Novel POLG mutations in progressive external ophthalmoplegia mimicking mitochondrial neurogastrointestinal encephalomyopathy." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/18546365", "http://www.ncbi.nlm.nih.gov/pubmed/12825077", "http://www.ncbi.nlm.nih.gov/pubmed/22647225", "http://www.ncbi.nlm.nih.gov/pubmed/15351195", "http://www.ncbi.nlm.nih.gov/pubmed/20927567" ]

[]

[]

[ "Ιvabradine decreases heart rate and reduces myocardial oxygen demand, increases diastolic perfusion time and improves energetics in ischemic myocardium. Ivabradine protects the myocardium during ischemia, improves left ventricular function in heart failure and reduces remodeling following myocardial infarction. It improves prognosis in patients with coronary artery disease, left ventricular dysfunction and heart rate ≥70 beats per minute, as well as in patients with heart failure and left ventricular dysfunction. The beneficial effects of ivabradine may be due to the reversal of electrophysiological cardiac remodelling in post-MI rats by reduction of functional overexpression of HCN channels. Furthermore, the improvement of cardiac function is related not only to the HR reduction per se but also to modifications in the extracellular matrix." ]

[]

[ "Ivabradine may be important for the improvement of clinical outcomes in patients with LV systolic dysfunction and heart rate ≥ 70 b.p.m., whatever the primary clinical presentation (CAD or HF) or clinical status (NYHA class).", "Treatment with ivabradine was associated with a 13% relative risk reduction for the composite of cardiovascular mortality or HF hospitalization (P < 0.001 vs. placebo); this was driven by HF hospitalizations (19%, P < 0.001). ", "Ivabradine (IVA), a pure HR lowering drug, reduces the demand of myocardial oxygen during exercise, contributes to the restoration of oxygen balance and is therefore beneficial in chronic CVD. No relevant negative effects have been observed on cardiac conduction, contractility, relaxation, repolarization or blood pressure (BP).", "The most significant results were obtained in the subgroup of patients with life-limiting exertional angina. In this group, ivabradine significantly reduced the primary endpoint, a composite of cardiovascular death, hospitalization for fatal and nonfatal acute myocardial infarction (AMI) or heart failure, by 24%, and hospitalizations for AMI by 42%. In the subgroup of patients with baseline heart rate >70 bpm, hospitalizations for AMI and revascularization were reduced by 73% and 59%, respectively", "Indeed, heart rate reduction with ivabradine, a selective and specific I(f) inhibitor, reduces myocardial oxygen demand, increases diastolic perfusion time and improves energetics in ischemic myocardium. Ivabradine protects the myocardium during ischemia, improves left ventricular function in heart failure and reduces remodeling following myocardial infarction. It improves prognosis in patients with coronary artery disease, left ventricular dysfunction and heart rate ≥70 beats per minute, as well as in patients with heart failure and left ventricular dysfunction.", "The beneficial effects of ivabradine may be due to the reversal of electrophysiological cardiac remodelling in post-MI rats by reduction of functional overexpression of HCN channels. This is attributable to transcriptional and post-transcriptional mechanisms.", "Addition of ivabradin to standard treatment of SCCF after MI promoted less frequency of hospitalizations, recurrent non-fatal MI, fatal cardiovascular events. This effect was especially strong in high baseline HR.", "The most important finding of the study was that patients with high baseline HR had an increase in serious cardiovascular events including death (34%), hospital admission secondary to congestive heart failure (53%), acute myocardial infarction (46%), or revascularization procedure (38%). In addition, in the subset analysis focusing on patients with baseline HR > or =70 bpm and left ventricular ejection fraction <40% the agent resulted in a 36% decrease in hospital admissions secondary to fatal and nonfatal myocardial infarction and a 30% decrease in coronary revascularization.", "In the subgroup of patients with a baseline heart rate > or =70 bpm, treatment with ivabradine resulted in a significant, 36% reduction in the risk of myocardial infarction and a 20% reduction in the need for coronary revascularisation. Ivabradine was well tolerated, with an increased rate of treatment discontinuation, mainly due to bradycardia, compared with placebo.", "Ivabradine did not significantly affect the combined primary endpoint. Significant reduction by 36% (p = 0.001) in myocardial infarction and by 30% (p = 0.016) in coronary revascularization was observed in the pre-defined subgroup of patients with heart rate > or = 70/min. ", "In conclusion, these data indicated that HR reduction by Iva prevents the worsening of LV dysfunction and remodeling that may be related to a downregulation of cardiac renin-angiotensin-aldosterone system transcripts.", "Interstitial fibrosis in the MI-remote LV was markedly reduced by Iva (4.0 +/- 0.1 vs. 1.8 +/- 0.1%, P < 0.005). ", "Although both metoprolol and ivabradine comparably prevented post-MI deterioration of haemodynamic function in the rat, metoprolol had additional potentially beneficial effects; it prevented LV dilation and hypertrophy, chronotropic incompetence, strongly increased contractility of isolated cardiomyocytes, and prevented the potentially proarrhythmic increase in NCX activity.", "In rats with CHF, long-term HRR induced by the selective I(f) inhibitor ivabradine improves LV function and increases stroke volume, preserving cardiac output despite the HRR. The improvement of cardiac function is related not only to the HRR per se but also to modifications in the extracellular matrix and/or function of myocytes as a consequence of long-term HRR." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/21838751", "http://www.ncbi.nlm.nih.gov/pubmed/19074674", "http://www.ncbi.nlm.nih.gov/pubmed/18310678", "http://www.ncbi.nlm.nih.gov/pubmed/23067195", "http://www.ncbi.nlm.nih.gov/pubmed/18757088", "http://www.ncbi.nlm.nih.gov/pubmed/20000882", "http://www.ncbi.nlm.nih.gov/pubmed/19664404", "http://www.ncbi.nlm.nih.gov/pubmed/14981003", "http://www.ncbi.nlm.nih.gov/pubmed/23096376", "http://www.ncbi.nlm.nih.gov/pubmed/21878041", "http://www.ncbi.nlm.nih.gov/pubmed/19514618", "http://www.ncbi.nlm.nih.gov/pubmed/22416440", "http://www.ncbi.nlm.nih.gov/pubmed/19129742", "http://www.ncbi.nlm.nih.gov/pubmed/23536611", "http://www.ncbi.nlm.nih.gov/pubmed/18621770", "http://www.ncbi.nlm.nih.gov/pubmed/19411283", "http://www.ncbi.nlm.nih.gov/pubmed/20028694", "http://www.ncbi.nlm.nih.gov/pubmed/23394554" ]

[]

[ "http://www.biosemantics.org/jochem#4266225", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009203", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D054143" ]

[ "Wilson's disease (WD) is an autosomal recessive disorder." ]

[ "autosomal recessive" ]

[ "The disease has an autosomal recessive mode of inheritance, and is characterized by excessive copper deposition, predominantly in the liver and brain.", " The inheritance is autosomal recessive. ", "Wilson's disease (WD), or hepatolenticular degeneration, is an autosomal recessive inheritance disorder of copper metabolism caused by ATP7B gene mutation. ", "Inheritance seems most likely to be autosomal recessive", "When familial, it is inherited recessively and has been linked to chromosome 20. ", "Inheritance of a pair of alleles of an autosomal recessive gene on chromosome 13 is necessary and sufficient to cause such copper accumulation in WD; reducing the dietary intake of copper cannot prevent the development of WD. ", "Wilson's disease is a treatable movement disorder with autosomal recessive inheritance which is associated with severe morbidity and mortality if not treated early. ", "The patient was considered heterozygote for hemochromatosis on the basis of the autosomal recessive inheritance for hemochromatosis, the frequency of the hemochromatosis gene, and the laboratory parameters defining her iron overload. ", "Wilson's disease (WD) is an autosomal recessive disorder of copper accumulation leading to liver and/or brain damage. ", "Autosomal recessive inheritance indicates that siblings of affected patients are at 25% risk of having the disease. ", "Wilson's disease is a rare genetic disorder of copper metabolism with autosomal recessive inheritance.", "Recessive inheritance is, however, supported. ", "The autosomal recessive mode of inheritance strongly suggests that mutation of a single gene causes the impairment of both caeruloplasmin synthesis and biliary copper excretion.", "This is consistent with the autosomal-recessive pattern of inheritance", "The overall sex ratio of patients was nearly 1:1, and genetic analysis of 20 families confirmed an autosomal recessive mode of inheritance. ", "Dermatoglyphics of 11 patients with Wilson's disease and 16 of their clinically asymptomatic relatives of first degree were investigated; 11 of the latter ones were heterozygous in agreement with the turn over rates of Cu-67, 12 under the assumption of autosomal recessive inheritance." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/838566", "http://www.ncbi.nlm.nih.gov/pubmed/12152840", "http://www.ncbi.nlm.nih.gov/pubmed/20662462", "http://www.ncbi.nlm.nih.gov/pubmed/16932613", "http://www.ncbi.nlm.nih.gov/pubmed/1248830", "http://www.ncbi.nlm.nih.gov/pubmed/22610954", "http://www.ncbi.nlm.nih.gov/pubmed/2724779", "http://www.ncbi.nlm.nih.gov/pubmed/8615372", "http://www.ncbi.nlm.nih.gov/pubmed/1940586", "http://www.ncbi.nlm.nih.gov/pubmed/6620327", "http://www.ncbi.nlm.nih.gov/pubmed/8186659", "http://www.ncbi.nlm.nih.gov/pubmed/759736", "http://www.ncbi.nlm.nih.gov/pubmed/6109943" ]

[ { "p": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseasome/diseaseSubtypeOf", "s": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseases/4181", "o": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseases/1198" }, { "p": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseasome/name", "s": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseases/1198", "o": "Wilson_disease" }, { "p": "http://www.w3.org/2004/02/skos/core#exactMatch", "s": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseases/1198", "o": "http://www.dbpedia.org/resource/Wilson%27s_disease" }, { "p": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseasome/name", "s": "http://www4.wiwiss.fu-berlin.de/diseasome/resource/diseases/4181", "o": "Wilson disease, 277900" } ]

[ "http://www.disease-ontology.org/api/metadata/DOID:4", "http://www.disease-ontology.org/api/metadata/DOID:893", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=diseases_category", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D006527", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D040582", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004194", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D014918", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D020739", "http://www.disease-ontology.org/api/metadata/DOID:2214" ]

[ "Yes. There is strong evidence that splicing and transcription are intimately coupled in metazoans, with genome wide surveys show that most splicing occurs during transcription. Chromatin structure, RNA polymerase dynamics, and recruitment of splicing factors through the transcriptional machinery are factors that explain a role for transcription in the regulation of splicing." ]

[ "yes" ]

[ ", as splicing is often cotranscriptional, a complex picture emerges in which splicing regulation not only depends on the balance of splicing factor binding to their pre-mRNA target sites but also on transcription-associated features such as protein recruitment to the transcribing machinery and elongation kinetics.", "recent evidence shows that chromatin structure is another layer of regulation that may act through various mechanisms", "hese span from regulation of RNA polymerase II elongation, which ultimately determines splicing decisions, to splicing factor recruitment by specific histone marks.", "Chromatin may not only be involved in alternative splicing regulation but in constitutive exon recognition as well", "Moreover, splicing was found to be necessary for the proper 'writing' of particular chromatin signatures, giving further mechanistic support to functional interconnections between splicing, transcription and chromatin structure.", "These links between chromatin configuration and splicing raise the intriguing possibility of the existence of a memory for splicing patterns to be inherited through epigenetic modifications.", "Spliceosome assembly occurs co-transcriptionally, raising the possibility that DNA structure may directly influence alternative splicing.", "upporting such an association, recent reports have identified distinct histone methylation patterns, elevated nucleosome occupancy and enriched DNA methylation at exons relative to introns", "Moreover, the rate of transcription elongation has been linked to alternative splicing.", "ere we provide the first evidence that a DNA-binding protein, CCCTC-binding factor (CTCF), can promote inclusion of weak upstream exons by mediating local RNA polymerase II pausing both in a mammalian model system for alternative splicing, CD45, and genome-wide", "We recently showed that cotranscriptional splicing occurs efficiently in Drosophila,", "In recent years it became apparent that splicing is predominantly cotranscriptional", "To determine the prevalence of cotranscriptional splicing in Drosophila, we sequenced nascent RNA transcripts from Drosophila S2 cells as well as from Drosophila heads. Eighty-seven percent of the introns assayed manifest >50% cotranscriptional splicing. The remaining 13% are cotranscriptionally spliced poorly or slowly, with ∼3% being almost completely retained in nascent pre-mRNA.", "We estimate that > or =90% of endogenous yeast splicing is posttranscriptional, consistent with an analysis of posttranscriptional snRNP-associated pre-mRNA.", "Notably, the topoisomerase I inhibitor camptothecin, which stalls elongating Pol II, increased cotranscriptional splicing factor accumulation and splicing in parallel. This provides direct evidence for a kinetic link between transcription, splicing factor recruitment and splicing catalysis.", "Recent evidence indicates that transcriptional elongation and splicing can be influenced reciprocally: Elongation rates control alternative splicing and splicing factors can, in turn, modulate pol II elongation.", "The presence of transcription factors in the spliceosome and the existence of proteins, such as the coactivator PGC-1, with dual activities in splicing and transcription can explain the links between both processes and add a new level of complexity to the regulation of gene expression in eukaryotes." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/20808788", "http://www.ncbi.nlm.nih.gov/pubmed/23074139", "http://www.ncbi.nlm.nih.gov/pubmed/23097425", "http://www.ncbi.nlm.nih.gov/pubmed/17189193", "http://www.ncbi.nlm.nih.gov/pubmed/21964334", "http://www.ncbi.nlm.nih.gov/pubmed/16921380", "http://www.ncbi.nlm.nih.gov/pubmed/15870275", "http://www.ncbi.nlm.nih.gov/pubmed/22479188", "http://www.ncbi.nlm.nih.gov/pubmed/22975042", "http://www.ncbi.nlm.nih.gov/pubmed/15905409", "http://www.ncbi.nlm.nih.gov/pubmed/21095588", "http://www.ncbi.nlm.nih.gov/pubmed/16172632", "http://www.ncbi.nlm.nih.gov/pubmed/15383674", "http://www.ncbi.nlm.nih.gov/pubmed/22156210", "http://www.ncbi.nlm.nih.gov/pubmed/23209445", "http://www.ncbi.nlm.nih.gov/pubmed/16769980" ]

[]

[]

[ "Facioscapulohumeral muscular dystrophy has an autosomal dominant inheritance pattern." ]

[ "autosomal dominant" ]

[ "autosomal dominant FSHD1", "Facioscapulohumeral muscular dystrophy (FSHD) is a neuromuscular disease, characterized by an autosomal dominant mode of inheritance, facial involvement, and selectivity and asymmetry of muscle involvement.", "Facioscapulohumeral dystrophy (FSHD) is an autosomal-dominant disorder characterized by weakness of the face, upper arm, shoulder, and lower limb musculature, with an onset between the first and third decades. ", "Clinical diagnosis is made from the distinctive pattern of weakness, autosomal-dominant inheritance, and confirmed by genetic testing.", " In one family together with prenatal diagnosis founder mutation in FSHD A1 gene was detected, according to the autosomal dominant (AD) inheritance.", "Facioscapulohumeral muscular dystrophy (FSHD) is a primary muscle disorder with autosomal dominant inheritance.", "Facioscapulohumeral muscular dystrophy (FSHD) is a slowly progressive myopathy with autosomal dominant inheritance remarkable for its early involvement of facial musculature.", "Consensual diagnostic criteria for facioscapulohumeral dystrophy (FSHD) include onset of the disease in facial or shoulder girdle muscles, facial weakness in more than 50% of affected family members, autosomal dominant inheritance in familial cases, and evidence of myopathic disease in at least one affected member without biopsy features specific to alternative diagnoses", "Facioscapulohumeral dystrophy (FSHD) is an autosomal-dominant muscular disorder associated with a short (<35 kb) EcoRI/BlnI fragment resulting from deletion of an integral number of units of a 3.3-kb repeat located at 4q35.", "In 139 families, dominant inheritance was observed in 97, a pattern compatible with germline mosaicism in 6, while sporadic cases were found in 36 families. ", "In 139 families, dominant inheritance was observed in 97, a pattern compatible with germline mosaicism in 6, while sporadic cases were found in 36 families." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/10487912", "http://www.ncbi.nlm.nih.gov/pubmed/15307599", "http://www.ncbi.nlm.nih.gov/pubmed/10969520", "http://www.ncbi.nlm.nih.gov/pubmed/19248726", "http://www.ncbi.nlm.nih.gov/pubmed/10864616", "http://www.ncbi.nlm.nih.gov/pubmed/7739631", "http://www.ncbi.nlm.nih.gov/pubmed/22551571", "http://www.ncbi.nlm.nih.gov/pubmed/22525183", "http://www.ncbi.nlm.nih.gov/pubmed/21795275", "http://www.ncbi.nlm.nih.gov/pubmed/23573591" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D040582", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D014918" ]

[ "Yes, Alu elements were found to be hypomethylated in breast cancer, especially in the HER2-enriched subtype. Furthermore, Alu hypomethylation was identified as a late event during breast cancer progression, and in invasive breast cancer, tended to be associated with negative estrogen receptor status and poor disease-free survival of the patients.", "Alu and LINE-1 hypomethylation is associated with HER2 enriched subtype of breast cancer " ]

[ "yes" ]

[ "Alu and LINE-1 hypomethylation is associated with HER2 enriched subtype of breast cancer", "In IBC, Alu hypomethylation correlated with negative estrogen receptor (ER) status", "In survival analyses, low Alu methylation status tended to be associated with poor disease-free survival of the patients.", "Alu hypomethylation is probably a late event during breast cancer progression", "prominent hypomethylation of Alu and LINE-1 in HER2 enriched subtype may be related to chromosomal instability of this specific subtype.", "DNA methylation for three repetitive elements (LINE1, Sat2 and Alu) were analyzed in invasive ductal carcinoma of the breast, paired adjacent normal tissue and WBC from 40 breast cancer patients", "DNA methylation for the three repetitive elements was lower in tumor compared to adjacent tissue and WBC DNA." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/20682973", "http://www.ncbi.nlm.nih.gov/pubmed/24971511" ]

[]

[ "http://www.disease-ontology.org/api/metadata/DOID:1612" ]

[ "Junctin is a major transmembrane protein in cardiac junctional sarcoplasmic reticulum, which forms a quaternary complex with the ryanodine receptor (Ca(2+) release channel), triadin, and calsequestrin. ", "Calsequestrin (CSQ) is a Ca(2+) storage protein that interacts with triadin (TRN), the ryanodine receptor (RyR), and junctin (JUN) to form a macromolecular tetrameric Ca(2+) signaling complex in the cardiac junctional sarcoplasmic reticulum (SR). Junctin, calsequestrin, triadin, and the ryanodine receptor form a quaternary complex that may be required for normal operation of Ca2+ release." ]

[ "Ryanodine receptor", "RyR", "Calsequestrin", "CASQ", "CSQ", "Triadin", "TrD", "TRN", "Junctin", "JCN", "JnC", "JUN" ]

[ "Calsequestrin (CSQ) is a Ca(2+) storage protein that interacts with triadin (TRN), the ryanodine receptor (RyR), and junctin (JUN) to form a macromolecular tetrameric Ca(2+) signaling complex in the cardiac junctional sarcoplasmic reticulum (SR).", "The decrease of CASQ2 is associated with a reduction in the levels of Triadin (TrD) and Junctin (JnC), two proteins that form, with CASQ2 and RyR2, a macromolecular complex devoted to control of calcium release from the sarcoplasmic reticulum.", "Triadin and junctin are integral sarcoplasmic reticulum membrane proteins that form a macromolecular complex with the skeletal muscle ryanodine receptor (RyR1) but their roles in skeletal muscle calcium homeostasis remain incompletely understood.", "Junctin, a 26 kDa intra-sarcoplasmic reticulum (SR) protein, forms a quaternary complex with triadin, calsequestrin and the ryanodine receptor (RyR) at the junctional SR membrane. ", "In cardiac muscle, junctin forms a quaternary protein complex with the ryanodine receptor (RyR), calsequestrin, and triadin 1 at the luminal face of the junctional sarcoplasmic reticulum (jSR). By binding directly the RyR and calsequestrin, junctin may mediate the Ca(2+)-dependent regulatory interactions between both proteins.", "Calsequestrin, the major calcium sequestering protein in the sarcoplasmic reticulum of muscle, forms a quaternary complex with the ryanodine receptor calcium release channel and the intrinsic membrane proteins triadin and junctin. ", "Junctin is a transmembrane protein of the cardiac junctional sarcoplasmic reticulum (SR) that binds to the ryanodine receptor, calsequestrin, and triadin 1. This quaternary protein complex is thought to facilitate SR Ca2+ release.", "In mammalian striated muscles, ryanodine receptor (RyR), triadin, junctin, and calsequestrin form a quaternary complex in the lumen of sarcoplasmic reticulum. Such intermolecular interactions contribute not only to the passive buffering of sarcoplasmic reticulum luminal Ca2+, but also to the active Ca2+ release process during excitation-contraction coupling. ", "Junctin is a major transmembrane protein in cardiac junctional sarcoplasmic reticulum, which forms a quaternary complex with the ryanodine receptor (Ca(2+) release channel), triadin, and calsequestrin. ", "Triadin 1 is a major transmembrane protein in cardiac junctional sarcoplasmic reticulum (SR), which forms a quaternary complex with the ryanodine receptor (Ca(2+) release channel), junctin, and calsequestrin.", "Several key proteins have been localized to junctional sarcoplasmic reticulum which are important for Ca2+ release. These include the ryanodine receptor, triadin, and calsequestrin, which may associate into a stable complex at the junctional membrane. We recently purified and cloned a fourth component of this complex, junctin, which exhibits homology with triadin and is the major 125I-calsequestrin-binding protein detected in cardiac sarcoplasmic reticulum vesicles", "By a combination of approaches including calsequestrin-affinity chromatography, filter overlay, immunoprecipitation assays, and fusion protein binding analyses, we find that junctin binds directly to calsequestrin, triadin, and the ryanodine receptor. ", "Taken together, these results suggest that junctin, calsequestrin, triadin, and the ryanodine receptor form a quaternary complex that may be required for normal operation of Ca2+ release.", "Calsequestrin, the major calcium sequestering protein in the sarcoplasmic reticulum of muscle, forms a quaternary complex with the ryanodine receptor calcium release channel and the intrinsic membrane proteins triadin and junctin.", "Junctin, a 26 kDa intra-sarcoplasmic reticulum (SR) protein, forms a quaternary complex with triadin, calsequestrin and the ryanodine receptor (RyR) at the junctional SR membrane.", "Junctin (JCN), a 26-kd sarcoplasmic reticulum (SR) transmembrane protein, forms a quaternary protein complex with the ryanodine receptor, calsequestrin, and triadin in the SR lumen of cardiac muscle.", "Junctin (JCN), a 26-kd sarcoplasmic reticulum (SR) transmembrane protein, forms a quaternary protein complex with the ryanodine receptor, calsequestrin, and triadin in the SR lumen of cardiac muscle", "Calsequestrin, the major calcium sequestering protein in the sarcoplasmic reticulum of muscle, forms a quaternary complex with the ryanodine receptor calcium release channel and the intrinsic membrane proteins triadin and junctin", "Junctin is a major transmembrane protein in cardiac junctional sarcoplasmic reticulum, which forms a quaternary complex with the ryanodine receptor (Ca(2+) release channel), triadin, and calsequestrin." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/12909320", "http://www.ncbi.nlm.nih.gov/pubmed/11069905", "http://www.ncbi.nlm.nih.gov/pubmed/15205169", "http://www.ncbi.nlm.nih.gov/pubmed/22298808", "http://www.ncbi.nlm.nih.gov/pubmed/22025663", "http://www.ncbi.nlm.nih.gov/pubmed/18620751", "http://www.ncbi.nlm.nih.gov/pubmed/18206802", "http://www.ncbi.nlm.nih.gov/pubmed/16289269", "http://www.ncbi.nlm.nih.gov/pubmed/15731387", "http://www.ncbi.nlm.nih.gov/pubmed/14638677", "http://www.ncbi.nlm.nih.gov/pubmed/9287354", "http://www.ncbi.nlm.nih.gov/pubmed/22427521" ]

[]

[ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0065003", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D020836", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D019837" ]

[ "Hydrophilic Interaction Chromatography (HILIC)" ]

[ "Hydrophilic Interaction Chromatography" ]

[ "hydrophilic interaction liquid chromatography-tandem mass spectrometry (HILIC LC-MS/MS) method", "Hydrophilic-interaction liquid chromatography (HILIC) is a widely used technique for small polar molecule analysis ", "hydrophilic-interaction LC (HILIC)", "A hydrophilic interaction liquid chromatography-tandem mass spectrometry (HILIC LC-MS/MS) method ", "Hydrophilic Interaction Chromatography (HILIC) ", "n this study a hydrophilic interaction chromatographic (HILIC) method " ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/21737084", "http://www.ncbi.nlm.nih.gov/pubmed/23217321", "http://www.ncbi.nlm.nih.gov/pubmed/22946920", "http://www.ncbi.nlm.nih.gov/pubmed/23073287", "http://www.ncbi.nlm.nih.gov/pubmed/21238772", "http://www.ncbi.nlm.nih.gov/pubmed/21316059" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D002845" ]

[ "TRH improves myocardial contractility" ]

[]

[ "Acute intravenous administration of TRH to rats with ischemic cardiomyopathy caused a significant increase in heart rate, mean arterial pressure, cardiac output, stroke volume, and cardiac contractility", "TRH can enhance cardiomyocyte contractility in vivo.", "TRH in the range of 0.1-10 mumol/l was found to exert a positive inotropic effect on cardiac contractility", "Thyrotropin-releasing hormone (TRH) improved mean arterial pressure (MAP) and myocardial contractility (dp/dtmax, -dp/dtmax, Vpm, and Vmax)", "TRH improves cardiac contractility, cardiac output, and hemodynamics", "Thyrotropin-releasing hormone (TRH) could improve mean arterial pressure (MAP), myocardial contractile parameters (+/- dp/dtmax, Vpm and Vmax)", "TRH increased the contractile force of muscles dose-dependently without changing the time course of contraction", "TRH potentiated the response of contractile force to increasing extracellular Ca2+ concentration.", "TRH has a positive inotropic effect at least partly due to an increase in the slow inward Ca2+ current", "Thus, TRH improves cardiac contractility, cardiac output, and hemodynamics during hemorrhagic shock." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/9225129", "http://www.ncbi.nlm.nih.gov/pubmed/1979356", "http://www.ncbi.nlm.nih.gov/pubmed/9088928", "http://www.ncbi.nlm.nih.gov/pubmed/15096458", "http://www.ncbi.nlm.nih.gov/pubmed/2848686", "http://www.ncbi.nlm.nih.gov/pubmed/1611701" ]

[]

[ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0008437", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D003285", "http://www.uniprot.org/uniprot/TRFR_MOUSE", "http://www.uniprot.org/uniprot/TRFR_CHICK", "http://www.disease-ontology.org/api/metadata/DOID:114", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D006331", "http://www.uniprot.org/uniprot/TRFR_SHEEP", "http://www.uniprot.org/uniprot/TRFR_RAT", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D006321", "http://www.biosemantics.org/jochem#4254151", "http://www.uniprot.org/uniprot/TRFR_HUMAN", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009200", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013973", "http://www.uniprot.org/uniprot/TRFR_BOVIN" ]

[ "Yes, the complete genome sequence of Arthrobacter (two strains) is deposited in GenBank." ]

[ "yes" ]

[]

[ "http://www.ncbi.nlm.nih.gov/pubmed/21677849", "http://www.ncbi.nlm.nih.gov/pubmed/23039946" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001173", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016678" ]

[ "The structure fold of the bromodomains is an all-alpha-helical fold, which includes a left-handed four-helix bundle topology, with two short additional helices in a long connecting loop." ]

[ "All-alpha-helical fold" ]

[ "These new studies also support the notion that functional diversity of a conserved bromodomain structural fold is achieved by evolutionary changes of structurally flexible amino-acid sequences in the ligand binding site such as the ZA and BC loops.", "Although the overall fold resembles the bromodomains from other proteins, significant differences can be found in loop regions, especially in the ZA loop in which a two amino acids insertion is involved in an uncommon pi-helix, termed piD", "In addition to a typical all-alpha-helical fold that was observed in the bromodomains, we observed for the first time a small beta-sheet in the ZA loop region of the BRG1 protein.", "Here, we report the crystal structure of the N-terminal bromodomain (BD1, residues 74-194) of human BRD2.", "This is the first observation of a homodimer among the known bromodomain structures, through the buried hydrophobic core region at the interface.", "The Brg1 bromodomain conserves the left-handed, four-helix bundle topology found in other bromodomain structures. However, the alphaZ helix of Brg1 bromodomain is about 4 residues shorter relative to previously published bromodomain structures.", "Here, we report the solution structure of BRD7 bromodomain determined by NMR spectroscopy, and its binding specificity revealed by NMR titration with several acetylated histone peptides.", "The 2.1 angstrom crystal structure of the double bromodomain reveals two side-by-side, four-helix bundles with a highly polarized surface charge distribution", "The structure has a left-handed four-helix bundle topology, with two short additional helices in a long connecting loop.", "The structure reveals an unusual left-handed up-and-down four-helix bundle. ", "In addition to a typical all-alpha-helical fold that was observed in the bromodomains, we observed for the first time a small beta-sheet in the ZA loop region of the BRG1 protein.", "In addition to a typical all-alpha-helical fold that was observed in the bromodomains," ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/17498659", "http://www.ncbi.nlm.nih.gov/pubmed/10365964", "http://www.ncbi.nlm.nih.gov/pubmed/17694091", "http://www.ncbi.nlm.nih.gov/pubmed/10827952", "http://www.ncbi.nlm.nih.gov/pubmed/17148447", "http://www.ncbi.nlm.nih.gov/pubmed/17582821", "http://www.ncbi.nlm.nih.gov/pubmed/11090279", "http://www.ncbi.nlm.nih.gov/pubmed/17274598", "http://www.ncbi.nlm.nih.gov/pubmed/17848202" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011506" ]

[ "Endoscopic examinations in autistic children have been reported to show : I or II reflux esophagitis, Achalasia, chronic gastritis and chronic duodenitis, mild acute and chronic inflammation of the small bowel and colorectum and Ileo-colonic lymphoid nodular hyperplasia (LNH). \nThe number of Paneth's cells in the duodenal crypts was found to be significantly elevated in autistic children compared with non-autistic control subjects. Low intestinal carbohydrate digestive enzyme activity was reported although there was no abnormality found in pancreatic function. Autistic children have ben reported to have an increased pancreatico-biliary fluid output after intravenous secretin administration." ]

[ "Reflux esophagitis", "Achalasia", "chronic gastritis", "chronic duodenitis", "inflammation of the small bowel and colorectum", "Ileo-colonic lymphoid nodular hyperplasia (LNH)" ]

[ "Autism and esophageal achalasia in childhood: a possible correlation?", "In the last case, a 15-year-old male underwent barium swallow and endoscopy that confirmed achalasia.", "Intestinal mucosal pathology, characterized by ileo-colonic lymphoid nodular hyperplasia (LNH) and mild acute and chronic inflammation of the colorectum, small bowel and stomach, has been reported in children with autistic spectrum disorder (ASD)", "Ileo-colonic LNH is a characteristic pathological finding in children with ASD and gastrointestinal symptoms, and is associated with mucosal inflammation.", "The data support the hypothesis that LNH is a significant pathological finding in ASD children.", "A relationship between autism and gastrointestinal (GI) immune dysregulation has been postulated based on incidence of GI complaints as well as macroscopically observed lymphonodular hyperplasia and microscopically determined enterocolitis in pediatric patients with autism.", "These data fail to support an association between autism and GI inflammation.", "Intestinal pathology, i.e., ileocolonic lymphoid nodular hyperplasia (LNH) and mucosal inflammation, has been described in children with developmental disorders.", "This study describes some of the endoscopic and pathological characteristics in a group of children with developmental disorders (affected children) that are associated with behavioral regression and bowel symptoms, and compares them with pediatric controls. METHODS: Ileocolonoscopy and biopsy were performed on 60 affected children (median age 6 yr, range 3-16; 53 male). Developmental diagnoses were autism (50 patients), Asperger's syndrome (five), disintegrative disorder (two), attention deficit hyperactivity disorder (ADHD) (one), schizophrenia (one), and dyslexia (one).", "Ileal LNH was present in 54 of 58 (93%) affected children and in five of 35 (14.3%) controls (p < 0.001). Colonic LNH was present in 18 of 60 (30%) affected children and in two of 37 (5.4%) controls (p < 0.01). Histologically, reactive follicular hyperplasia was present in 46 of 52 (88.5%) ileal biopsies from affected children and in four of 14 (29%) with UC, but not in non-IBD controls (p < 0.01). Active ileitis was present in four of 51 (8%) affected children but not in controls. Chronic colitis was identified in 53 of 60 (88%) affected children compared with one of 22 (4.5%) controls and in 20 of 20 (100%) with UC", "Thirty-six children (age: 5.7 +/- 2 years, mean +/- SD) with autistic disorder underwent upper gastrointestinal endoscopy with biopsies, intestinal and pancreatic enzyme analyses, and bacterial and fungal cultures", "Histologic examination in these 36 children revealed grade I or II reflux esophagitis in 25 (69.4%), chronic gastritis in 15, and chronic duodenitis in 24. The number of Paneth's cells in the duodenal crypts was significantly elevated in autistic children compared with non-autistic control subjects. Low intestinal carbohydrate digestive enzyme activity was reported in 21 children (58.3%), although there was no abnormality found in pancreatic function. Seventy-five percent of the autistic children (27/36) had an increased pancreatico-biliary fluid output after intravenous secretin administration. Nineteen of the 21 patients with diarrhea had significantly higher fluid output than those without diarrhea.", "Unrecognized gastrointestinal disorders, especially reflux esophagitis and disaccharide malabsorption, may contribute to the behavioral problems of the non-verbal autistic patients. The observed increase in pancreatico-biliary secretion after secretin infusion suggests an upregulation of secretin receptors in the pancreas and liver.", "three children with autistic spectrum disorders who underwent upper gastrointestinal endoscopy and intravenous administration of secretin to stimulate pancreaticobiliary secretion. All three had an increased pancreaticobiliary secretory response when compared with nonautistic patients (" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/11007230", "http://www.ncbi.nlm.nih.gov/pubmed/22607127", "http://www.ncbi.nlm.nih.gov/pubmed/16003132", "http://www.ncbi.nlm.nih.gov/pubmed/9585670", "http://www.ncbi.nlm.nih.gov/pubmed/10547242", "http://www.ncbi.nlm.nih.gov/pubmed/12907332" ]

[]

[ "http://www.disease-ontology.org/api/metadata/DOID:12849", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001321", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016099", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004724" ]

[ "Significant decreases and progressively higher reductions of systolic and diastolic blood pressure were observed after RSD. The complication rate was minimal.\nRenal sympathetic denervation also reduces heart rate, which is a surrogate marker of cardiovascular risk." ]

[]

[ "Significant decreases and progressively higher reductions of systolic and diastolic blood pressure were observed after RSD. The complication rate was minimal. ", "In conclusion, the RSD presents itself as an effective and safe approach to resistant hypertension.", "Renal sympathetic denervation delivers not only a decrease in blood pressure levels but also renal as well as systemic sympathetic nerve activity. The reduction in blood pressure appears to be sustained over 3 years after the procedure, which implies no counterregulatory mechanism or re-innervation of afferent renal sympathetic nerve so far.", "Renal sympathetic denervation not only reduces blood pressure but also renal as well as systemic sympathetic nerve activity in such patients. The reduction in blood pressure appears to be sustained over 3 years after the procedure, which suggests absence of re-innervation of renal sympathetic nerves. Safety appears to be adequate.", "Clinical trials of renal sympathetic denervation have shown significant reductions in blood pressure in these patients. Renal sympathetic denervation also reduces heart rate, which is a surrogate marker of cardiovascular risk. ", "Small studies suggest that RSD can produce dramatic blood pressure reductions: In the randomized Symplicity HTN-2 trial of 106 patients, the mean fall in blood pressure at 6 months in patients who received the treatment was 32/12 mm Hg. However, there are limitations to the evidence for RSD in the treatment of resistant hypertension. These include the small number of patients studied; the lack of any placebo-controlled evidence; the fact that blood pressure outcomes were based on office assessments, as opposed to 24-hour ambulatory monitoring; the lack of longer-term efficacy data; and the lack of long-term safety data.", "Clinical evaluation of selective renal sympathetic denervation demonstrated a decrease of renal norepinephrine spillover and renin activity, an increase of renal plasma flow, and has confirmed clinically significant, sustained reductions in blood pressure in patients with resistant hypertension.", "In addition to drug treatment, baroreceptor stimulation therapy and renal sympathetic denervation are promising new approaches in this group of patients.", "Early clinical evaluation with catheter-based, selective renal sympathetic denervation in patients with resistant hypertension has mechanistically correlated sympathetic efferent denervation with decreased renal norepinephrine spillover and renin activity, increased renal plasma flow, and has demonstrated clinically significant, sustained reductions in blood pressure. The SYMPLICITY HTN-3 Trial is a pivotal study designed as a prospective, randomized, masked procedure, single-blind trial evaluating the safety and effectiveness of catheter-based bilateral renal denervation for the treatment of uncontrolled hypertension despite compliance with at least 3 antihypertensive medications of different classes (at least one of which is a diuretic) at maximal tolerable doses.", "Novel procedure- and device-based strategies to control hypertension include renal sympathetic denervation and baroreflex sensitization." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/21247927", "http://www.ncbi.nlm.nih.gov/pubmed/22573363", "http://www.ncbi.nlm.nih.gov/pubmed/23176687", "http://www.ncbi.nlm.nih.gov/pubmed/23541665", "http://www.ncbi.nlm.nih.gov/pubmed/23774592", "http://www.ncbi.nlm.nih.gov/pubmed/24029963", "http://www.ncbi.nlm.nih.gov/pubmed/23890950", "http://www.ncbi.nlm.nih.gov/pubmed/23514712", "http://www.ncbi.nlm.nih.gov/pubmed/23819768" ]

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[ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013563", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013562", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D003714", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012077" ]

[ "c-Jun is phosphorylated by c-Jun NH2-terminal kinase (JNK).", "An in vitro kinase assay revealed that c-Jun phosphorylation is primarily mediated via activated c-Jun N-terminal protein kinase (JNK)." ]

[ "c-Jun NH2-terminal kinase", "JNK" ]

[ " c-Jun NH2-terminal kinase (JNK)", " c-jun N-terminal kinase (JNK) of mitogen-activated protein kinase (MAPK) family ", "-Jun N-terminal kinase (JNK)", "activated c-Jun N-terminal kinase (JNK)", "-Jun N-terminal kinase (JNK) mitogen-activated protein kinase (MAPK) signaling pathways", " c-Jun N-terminal kinases (JNK) ", " including c-Jun N-terminal kinase, c-Jun", "The c-Jun N-terminal kinase (JNK) is thought to be involved in inflammation, proliferation and apoptosis. ", " c-Jun NH2-terminal protein kinases (JNK), ", " c-Jun N-terminal kinase (JNK) phosphorylation, c-Jun phosphorylation", "JNK phosphorylated recombinant c-Jun at T91/T93 in a T95-dependent manner", " c-Jun N-terminal kinase (JNK) MAPKs (mitogen-activated protein kinases)", "c-Jun N-terminal kinases (JNKs) are a group of mitogen-activated protein kinase family members that are important in regulating cell growth, proliferation, and apoptosis.", "Jun and Fos transcriptional activities are also regulated by phosphorylation as a result of the activation of intracellular signaling cascades. In this regard, the phosphorylation of c-Jun by UV-induced JNK has been readily documented, whereas a role for Fos proteins in UV-mediated responses and the identification of Fos-activating kinases has remained elusive", "An in vitro kinase assay revealed that the resultant c-Jun phosphorylation was primarily mediated via activated c-Jun N-terminal protein kinase (JNK).", "The c-Jun N-terminal kinase (JNK) pathway forms part of the mitogen-activated protein kinase (MAPK) signaling pathways comprising a sequential three-tiered kinase cascade. ", "The c-Jun N-terminal kinases (JNKs) are members of the mitogen-activated protein kinase (MAPK) family and are activated by environmental stress.", "JNK phosphorylates and regulates the activity of transcription factors other than c-Jun, including ATF2, Elk-1, p53 and c-Myc and non-transcription factors, such as members of the Bcl-2 family.", "A candidate for this extended family of MAP kinases is the c-Jun NH2-terminal kinase (Jnk), which binds to and phosphorylates the transcription factor c-Jun at the activating sites Ser-63 and Ser-73.", "An in vitro kinase assay revealed that the resultant c-Jun phosphorylation was primarily mediated via activated c-Jun N-terminal protein kinase (JNK)", "A candidate for this extended family of MAP kinases is the c-Jun NH2-terminal kinase (Jnk), which binds to and phosphorylates the transcription factor c-Jun at the activating sites Ser-63 and Ser-73" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/24113186", "http://www.ncbi.nlm.nih.gov/pubmed/24300195", "http://www.ncbi.nlm.nih.gov/pubmed/24272171", "http://www.ncbi.nlm.nih.gov/pubmed/24291243", "http://www.ncbi.nlm.nih.gov/pubmed/24252081", "http://www.ncbi.nlm.nih.gov/pubmed/15228586", "http://www.ncbi.nlm.nih.gov/pubmed/23028407", "http://www.ncbi.nlm.nih.gov/pubmed/24285252", "http://www.ncbi.nlm.nih.gov/pubmed/23385061", "http://www.ncbi.nlm.nih.gov/pubmed/24321566", "http://www.ncbi.nlm.nih.gov/pubmed/23147205", "http://www.ncbi.nlm.nih.gov/pubmed/8607977", "http://www.ncbi.nlm.nih.gov/pubmed/24139673", "http://www.ncbi.nlm.nih.gov/pubmed/24321066", "http://www.ncbi.nlm.nih.gov/pubmed/15637069", "http://www.ncbi.nlm.nih.gov/pubmed/24270002", "http://www.ncbi.nlm.nih.gov/pubmed/24144051", "http://www.ncbi.nlm.nih.gov/pubmed/15708845" ]

[]

[ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0007257", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0007258", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016755" ]

[ "TAILS stands for \"Terminal Amine Isotopic Labeling of Substrates\"" ]

[ "TAILS: Terminal Amine Isotopic Labeling of Substrates" ]

[ ". It is important to identify what proteins are substrates of proteases and where their cleavage sites are so as to reveal the molecular mechanisms and specificity of signaling. ", "It is important to identify what proteins are substrates of proteases and where their cleavage sites are so as to reveal the molecular mechanisms and specificity of signaling.", "analysis of N- terminomics data generated by terminal amine isotopic labeling of substrates (TAILS) enables high confidence peptide to protein assignment, protein N-terminal characterization and annotation, and for protease analysis readily allows protease substrate discovery with high confidence.", "Several approaches to studying proteolytic activity as it relates to biology, pathophysiology, and drug therapy have been published, including the recently described terminal amine isotopic labeling of substrates (TAILS) strategy by Kleifeld and colleagues", " The degradomics screen terminal amine isotopic labeling of substrates (TAILS), which enriches for neo-N-terminal peptides of cleaved substrates, was used to identify 58 new native substrates in fibroblast secretomes after incubation with MT6-MMP. ", " Here we present in detail the steps required to perform our recently described approach we call Terminal Amine Isotopic Labeling of Substrates (TAILS), a combined N-terminomics and protease substrate discovery degradomics platform for the simultaneous quantitative and global analysis of the N-terminome and proteolysis in one MS/MS experiment. ", "Identification of proteolytic products and natural protein N-termini by Terminal Amine Isotopic Labeling of Substrates (TAILS).", " Incorporating iTRAQ whole protein labeling with terminal amine isotopic labeling of substrates (iTRAQ-TAILS) to enrich the N-terminome by negative selection of the blocked mature original N-termini and neo-N-termini has many advantages. " ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/22577022", "http://www.ncbi.nlm.nih.gov/pubmed/23667905", "http://www.ncbi.nlm.nih.gov/pubmed/21604129", "http://www.ncbi.nlm.nih.gov/pubmed/20305284", "http://www.ncbi.nlm.nih.gov/pubmed/22367194" ]

[]

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

[ "Yes, AKT1 mutation occurs in meningiomas." ]

[ "yes" ]

[ "The recent identification of somatic mutations in components of the SHH-GLI1 and AKT1-MTOR signaling pathways indicates the potential for cross talk of these pathways in the development of meningiomas.", "A mutation in PIK3CA or AKT1 was found in around 9 % of the cases.", "AKT1E17K mutations cluster with meningothelial and transitional meningiomas and can be detected by SFRP1 immunohistochemistry.", "AKT1E17K mutations were exclusively seen in meningiomas and occurred in 65 of 958 of these tumors. A strong preponderance was seen in the variant of meningothelial meningioma WHO grade I of basal and spinal localization. In contrast, AKT1E17K mutations were rare in WHO grade II and absent in WHO grade III meningiomas. ", "We observed strong up-regulation of SFRP1 expression in all meningiomas with AKT1E17K mutation and in HEK293 cells after transfection with mutant AKT1E17K, but not in meningiomas and HEK293 cells lacking this mutation.", "SMO and AKT1 mutations occur in non-NF2 meningiomas.", "Recurrent mutations in SMO and AKT1 are mutually exclusive with NF2 loss in meningioma.", "Genomic sequencing of meningiomas identifies oncogenic SMO and AKT1 mutations.", " A subset of meningiomas lacking NF2 alterations harbored recurrent oncogenic mutations in AKT1 (p.Glu17Lys) and SMO (p.Trp535Leu) and exhibited immunohistochemical evidence of activation of these pathways.", "Genomic analysis of non-NF2 meningiomas reveals mutations in TRAF7, KLF4, AKT1, and SMO.", "A subset of meningiomas lacking NF2 alterations harbored recurrent oncogenic mutations in AKT1 (p.Glu17Lys) and SMO (p.Trp535Leu) and exhibited immunohistochemical evidence of activation of these pathways.", "SMO and AKT1 mutations occur in non-NF2 meningiomas", "The recent identification of somatic mutations in components of the SHH-GLI1 and AKT1-MTOR signaling pathways indicates the potential for cross talk of these pathways in the development of meningiomas", "A subset of meningiomas lacking NF2 alterations harbored recurrent oncogenic mutations in AKT1 (p.Glu17Lys) and SMO (p.Trp535Leu) and exhibited immunohistochemical evidence of activation of these pathways", "Genomic analysis of non-NF2 meningiomas reveals mutations in TRAF7, KLF4, AKT1, and SMO", "Genomic sequencing of meningiomas identifies oncogenic SMO and AKT1 mutations", "Recurrent mutations in SMO and AKT1 are mutually exclusive with NF2 loss in meningioma", "A subset of meningiomas lacking NF2 alterations harbored recurrent oncogenic mutations in AKT1 (p.Glu17Lys) and SMO (p.Trp535Leu) and exhibited immunohistochemical evidence of activation of these pathways. These mutations were present in therapeutically challenging tumors of the skull base and higher grade. ", "A subset of meningiomas lacking NF2 alterations harbored recurrent oncogenic mutations in AKT1 (p.Glu17Lys) and SMO (p.Trp535Leu) and exhibited immunohistochemical evidence of activation of these pathways. " ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/25146167", "http://www.ncbi.nlm.nih.gov/pubmed/23475883", "http://www.ncbi.nlm.nih.gov/pubmed/23348505", "http://www.ncbi.nlm.nih.gov/pubmed/23334667", "http://www.ncbi.nlm.nih.gov/pubmed/24096618", "http://www.ncbi.nlm.nih.gov/pubmed/25857641" ]

[]

[ "http://www.biosemantics.org/jochem#4264173", "http://www.disease-ontology.org/api/metadata/DOID:3565", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009154", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D008579" ]

[ "Lacosamide is an anti-epileptic drug, licensed for refractory partial-onset seizures. In addition to this, it has demonstrated analgesic activity in various animal models. Apart from this, LCM has demonstrated potent effects in animal models for a variety of CNS disorders like schizophrenia and stress induced anxiety." ]

[ "epilepsy", "refractory epilepsy", "refractory partial-onset seizures", "analgesic", "CNS disorders" ]

[ "The current article presents a concise review of network theory and its application to the characterization of AED use in children with refractory epilepsy.", "Furthermore, first generation AEDs were often discontinued, while lacosamide and topiramate were most likely to be initiated. ", "Overall, there is compelling evidence that salivary TDM can be usefully applied so as to optimize the treatment of epilepsy with carbamazepine, clobazam, ethosuximide, gabapentin, lacosamide, lamotrigine, levetiracetam, oxcarbazepine, phenobarbital, phenytoin, primidone, topiramate, and zonisamide.", "The first examples are carbamazepine, gabapentin, and lacosamide as drugs well established in epilepsy market as well as drug candidates such as valnoctamide, and other valproic acid derivatives, novel biphenyl pyrazole derivatives, etc.", "Two additional AEDs, lacosamide and eslicarbazepine acetate, have been licensed recently for a more traditional indication, refractory partial-onset seizures. ", "A discussion is made of recent findings that the atypical antidepressant tianeptine increases CRMP2 expression, whereas other, neuroactive small molecules including the epilepsy drug lacosamide and the natural brain metabolite lanthionine ketimine appear to bind CRMP2 directly with concomitant affects on neural structure.", "Lacosamide (LCM) is a newer antiepileptic drug with a dual mode of action.", " It has shown potent and broad neuroprotective effects in vitro and in vivo animal models making it a potential candidate for long term treatment of epilepsy. In addition to this, it has demonstrated analgesic activity in various animal models. Apart from this, LCM has demonstrated potent effects in animal models for a variety of CNS disorders like schizophrenia and stress induced anxiety. ", "Clinical trials have also suggested that LCM is a safe, effective, and well tolerated adjunctive treatment for reduction of seizure frequency in patients with highly refractory, partial seizures.", "Lacosamide (LCM), (SPM 927, (R)-2-acetamido-N-benzyl-3-methoxypropionamide, previously referred to as harkoseride or ADD 234037) is a member of a series of functionalized amino acids that were specifically synthesized as anticonvulsive drug candidates. LCM has demonstrated antiepileptic effectiveness in different rodent seizure models and antinociceptive potential in experimental animal models that reflect distinct types and symptoms of neuropathic as well as chronic inflammatory pain.", "Recent results suggest that LCM has a dual mode of action underlying its anticonvulsant and analgesic activity.", "Currently, LCM is in a late stage of clinical development as an adjunctive treatment for patients with uncontrolled partial-onset seizures, and it is being assessed as monotherapy in patients with painful diabetic neuropathy. ", "Lacosamide was effective against sound-induced seizures in the genetically susceptible Frings mouse, against maximal electroshock test (MES)-induced seizures in rats and mice, in the rat hippocampal kindling model of partial seizures, and in the 6Hz model of psychomotor seizures in mice.", "Lacosamide was inactive against clonic seizures induced by subcutaneous administration of the chemoconvulsants pentylenetetrazol, bicuculline, and picrotoxin, but it did inhibit NMDA-induced seizures in mice and showed full efficacy in the homocysteine model of epilepsy.", "These results suggest that lacosamide may have the potential to be clinically useful for at least the treatment of generalized tonic-clonic and partial-onset epilepsies, and support ongoing clinical trials in these indications." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/23288091", "http://www.ncbi.nlm.nih.gov/pubmed/17461888", "http://www.ncbi.nlm.nih.gov/pubmed/23648276", "http://www.ncbi.nlm.nih.gov/pubmed/20677583", "http://www.ncbi.nlm.nih.gov/pubmed/21861814", "http://www.ncbi.nlm.nih.gov/pubmed/21301338", "http://www.ncbi.nlm.nih.gov/pubmed/21271304", "http://www.ncbi.nlm.nih.gov/pubmed/17433624" ]

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[ "http://www.biosemantics.org/jochem#4267957" ]

[ "Ewing sarcoma is the second most common bone malignancy in children and young adults. In almost 95% of the cases, it is driven by oncogenic fusion protein EWS/FLI1, which acts as an aberrant transcription factor, that upregulates or downregulates target genes, leading to cellular transformation." ]

[ "EWS/FLI1" ]

[ "Ewing sarcoma is the second most common bone malignancy in children and young adults. It is driven by oncogenic fusion proteins (i.e. EWS/FLI1) acting as aberrant transcription factors that upregulate and downregulate target genes, leading to cellular transformation", "EWS/FLI-1 oncoprotein subtypes impose different requirements for transformation and metastatic activity in a murine model", "Ewing sarcoma/primitive neuroectodermal tumors (EWS/PNET) are characterized by specific chromosomal translocations most often generating a chimeric EWS/FLI-1 gene", "The resulting EWS-FLI-1 fusion protein is believed to behave as an aberrant transcriptional activator that contributes to ESFT development by altering the expression of its target genes in a permissive cellular environment", "Herein, we show that the DNA repair protein and transcriptional cofactor, EYA3, is highly expressed in Ewing sarcoma tumor samples and cell lines compared with mesenchymal stem cells, the presumed cell-of-origin of Ewing sarcoma, and that it is regulated by the EWS/FLI1 fusion protein transcription factor", "The orphan nuclear receptor DAX1 is up-regulated by the EWS/FLI1 oncoprotein and is highly expressed in Ewing tumors", "The Ewing family of tumors harbors chromosomal translocations that join the N-terminal region of the EWS gene with the C-terminal region of several transcription factors of the ETS family, mainly FLI1, resulting in chimeric transcription factors that play a pivotal role in the pathogenesis of Ewing tumors. To identify downstream targets of the EWS/FLI1 fusion protein, we established 293 cells expressing constitutively either the chimeric EWS/FLI1 or wild type FLI1 proteins and used cDNA arrays to identify genes differentially regulated by EWS/FLI1", "The high levels of DAX1 found in Ewing tumors and its potent transcriptional repressor activity suggest that the oncogenic effect of EWS/FLI1 may be mediated, at least in part, by the up-regulation of DAX1 expression", "Herein, we show that the DNA repair protein and transcriptional cofactor, EYA3, is highly expressed in Ewing sarcoma tumor samples and cell lines compared with mesenchymal stem cells, the presumed cell-of-origin of Ewing sarcoma, and that it is regulated by the EWS/FLI1 fusion protein transcription factor.", "Ewing sarcoma family tumors (ESFT) are highly aggressive and highly metastatic tumors caused by a chromosomal fusion between the Ewing sarcoma protein (EWS) with the transcription factor FLI-1.", "EWS-FLI1 is a fusion protein that results from the pathognomonic translocation of Ewing sarcoma (ES).", "Chromosomal translocation that results in fusion of the genes encoding RNA-binding protein EWS and transcription factor FLI1 (EWS-FLI1) is pathognomonic for Ewing sarcoma.", "Eighty-five percent of Ewing sarcoma is characterized by the presence of the aberrant chimeric EWS/FLI1 fusion gene.", "Blocking the road, stopping the engine or killing the driver? Advances in targeting EWS/FLI-1 fusion in Ewing sarcoma as novel therapy.", "Fusion of the EWS gene to FLI1 produces a fusion oncoprotein that drives an aberrant gene expression program responsible for the development of Ewing sarcoma.", "Mosaic expression of the human EWS-FLI1 fusion protein in zebrafish caused the development of tumors with histology strongly resembling that of human Ewings sarcoma.", "Ewing sarcoma family of tumors (ESFT) is a group of aggressive pediatric malignancies driven by the EWS-FLI1 fusion protein, an aberrant transcription factor up-regulating specific target genes, such as neuropeptide Y (NPY) and its Y1 and Y5 receptors (Y5Rs).", "Ewing sarcoma is primarily caused by a t(11;22) chromosomal translocation encoding the EWS-FLI1 fusion protein.", "Herein, we show that the DNA repair protein and transcriptional cofactor, EYA3, is highly expressed in Ewing sarcoma tumor samples and cell lines compared with mesenchymal stem cells, the presumed cell-of-origin of Ewing sarcoma, and that it is regulated by the EWS/FLI1 fusion protein transcription factor.", "The EWS-ETS fusion is causative in the development of Ewing's tumour.", "The resulting EWS-FLI-1 fusion protein is believed to behave as an aberrant transcriptional activator that contributes to ESFT development by altering the expression of its target genes in a permissive cellular environment.", "EWS-FLI1 is an oncogenic fusion protein implicated in the development of Ewing's sarcoma family tumors (ESFT)", "Eighty-five percent of Ewing sarcoma is characterized by the presence of the aberrant chimeric EWS/FLI1 fusion gene", "Chromosomal translocation that results in fusion of the genes encoding RNA-binding protein EWS and transcription factor FLI1 (EWS-FLI1) is pathognomonic for Ewing sarcoma", "Together, our data reveal that EWSAT1 is a downstream target of EWS-FLI1 that facilitates the development of Ewing sarcoma via the repression of target genes", "Thus, we developed a highly validated transcriptional profile for the EWS/FLI fusion protein and identified a critical target gene in Ewing's sarcoma development.", "Our understanding of Ewing's sarcoma development mediated by the EWS/FLI fusion protein has been limited by a lack of knowledge regarding the tumor cell of origin", "Ewing's sarcomas are characterized by recurrent chromosomal translocations expressing EWS-ETS fusion proteins, the most common of which is EWS-FLI.(1-5) EWS-FLI is an oncogenic transcription factor that regulates genes involved in tumorigenesis.(6,7) Because the Ewing's sarcoma cell of origin remains unknown, a variety of model systems have been developed to study EWS-FLI fusions,(8-14) and multiple microarray experiments describing potential EWS-FLI target genes have been reported.(8,10,11,13,15-21) Each model has potential benefits and drawbacks, but a large-scale comparison of these has not been reported", "Most cases of Ewing's sarcoma express the EWS/FLI fusion protein" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/25432018", "http://www.ncbi.nlm.nih.gov/pubmed/21979944", "http://www.ncbi.nlm.nih.gov/pubmed/16206264", "http://www.ncbi.nlm.nih.gov/pubmed/18256529", "http://www.ncbi.nlm.nih.gov/pubmed/25162919", "http://www.ncbi.nlm.nih.gov/pubmed/19718047", "http://www.ncbi.nlm.nih.gov/pubmed/22241085", "http://www.ncbi.nlm.nih.gov/pubmed/24481407", "http://www.ncbi.nlm.nih.gov/pubmed/17250957", "http://www.ncbi.nlm.nih.gov/pubmed/25483190", "http://www.ncbi.nlm.nih.gov/pubmed/20691659", "http://www.ncbi.nlm.nih.gov/pubmed/22723308", "http://www.ncbi.nlm.nih.gov/pubmed/23750284", "http://www.ncbi.nlm.nih.gov/pubmed/16697960", "http://www.ncbi.nlm.nih.gov/pubmed/25401475", "http://www.ncbi.nlm.nih.gov/pubmed/17453169", "http://www.ncbi.nlm.nih.gov/pubmed/18485618", "http://www.ncbi.nlm.nih.gov/pubmed/23894528", "http://www.ncbi.nlm.nih.gov/pubmed/21680731" ]

[]

[ "http://www.disease-ontology.org/api/metadata/DOID:3368", "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" ]

[ "Hemolytic uremic syndrome (HUS) is a clinical syndrome characterized by the triad of anaemia, thrombocytopenia, renal failure." ]

[ "anaemia", "thrombocytopenia", "renal failure" ]

[ "Hemolytic uremic syndrome (HUS) is a clinical syndrome characterized by the triad of thrombotic microangiopathy, thrombocytopenia, and acute kidney injury.", "Atypical hemolytic uremic syndrome (aHUS) is a rare disease characterized by the triad of microangiopathic hemolytic anemia, thrombocytopenia, and acute renal failure.", "Atypical hemolytic uremic syndrome (aHUS) is a relatively rare disorder described by the triad of hemolytic anemia, thrombocytopenia, and renal failure.", "Until recently, atypical hemolytic uremic syndrome (aHUS), conventionally defined in the pediatric literature as a syndrome of the triad of renal failure, microangiopathic hemolytic anemia, and thrombocytopenia without a prodrome of hemorrhagic diarrhea, has received little attention in adult practice because the patients are commonly given the diagnosis of thrombotic thrombocytopenic purpura (TTP) or TTP/HUS and treated as TTP with plasma exchange, augmented in refractory cases with rituximab and sometimes even splenectomy. ", "Atypical hemolytic uremic syndrome (aHUS) is rare and comprises the triad of microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury. ", "Hemolyitic uremic syndrome (HUS), characterized by triad of acute kidney injury, thrombocytopenia, and hemolytic anemia, has considerable morbidity and mortality and is known to be associated with diarrheal illness. ", "Hemolytic uremic syndrome (HUS) is a rare thrombotic complication characterized by a triad of microangiopathic hemolytic anemia, thrombocytopenia, and acute renal failure.", "Until recently, atypical hemolytic uremic syndrome (aHUS), conventionally defined in the pediatric literature as a syndrome of the triad of renal failure, microangiopathic hemolytic anemia, and thrombocytopenia without a prodrome of hemorrhagic diarrhea, has received little attention in adult practice because the patients are commonly given the diagnosis of thrombotic thrombocytopenic purpura (TTP) or TTP/HUS and treated as TTP with plasma exchange, augmented in refractory cases with rituximab and sometimes even splenectomy.", "Hemolytic uremic syndrome consists of a triad of acquired hemolytic anemia, thrombocytopenia and renal failure.", "Hemolytic uremic syndrome (HUS) is a triad of microangiopathic hemolytic anemia, thrombocytopenia, and acute renal failure.", "The hemolytic-uremic syndrome consists of the triad of microangiopathic hemolytic anemia, thrombocytopenia, and renal failure.", "Atypical hemolytic uremic syndrome (aHUS) is characterized by the triad of microangiopathic hemolytic anemia, thrombocytopenia, and renal impairment.", "Hemolytic uremic syndrome is a rare condition compromising the clinical triad of acute renal failure, microangiopathic hemolytic anemia, and thrombocytopenia.", "Hemolytic Uremic Syndrome (HUS) consists ofa triad of acquired hemolytic anemia, thrombocytopenia, and renal failure that occurs acutely in otherwise healthy individuals.", "The hemolytic-uremic syndrome is a pathology characterized by a triad consisting of acute renal failure, microangiopathic hemolytic anemia and thrombocytopenia, with complications of the central nervous system arising in a considerable number of cases.", "Hemolytic uremic syndrome, one of the common causes of acute renal failure in children, is characterized by the triad of microangiopathy, haemolytic anemia, thrombocytopenia and acute renal failure.", "Hemolytic uremic syndrome (HUS) is a triad of microangiopathic hemolytic anemia, thrombocytopenia, and acute renal failure", "Hemolytic uremic syndrome (HUS) is a rare thrombotic complication characterized by a triad of microangiopathic hemolytic anemia, thrombocytopenia, and acute renal failure", "Hemolytic uremic syndrome (HUS) is a disorder characterized by the presence of the classic triad: microangiopathic hemolytic anemia, thrombocytopenia and acute renal injury", "Hemolytic uremic syndrome consists of a triad of acquired hemolytic anemia, thrombocytopenia and renal failure", "Hemolytic uremic syndrome (HUS) is a severe disease characterized by the clinical triad of hemolytic anemia, thrombocytopenia, and acute renal failure", "Hemolytic uremic syndrome is a rare condition compromising the clinical triad of acute renal failure, microangiopathic hemolytic anemia, and thrombocytopenia", "Hemolytic uremic syndrome is a triad of microangiopathic hemolytic anemia, thrombocytopenia, and acute renal failure", "Hemolytic uremic syndrome is a rare entity in patients with carcinoma and presents with a triad of renal insufficiency, microangiopathic hemolytic anemia, and thrombocytopenia", "Hemolytic Uremic Syndrome (HUS) consists ofa triad of acquired hemolytic anemia, thrombocytopenia, and renal failure that occurs acutely in otherwise healthy individuals", "Hemolytic Uremic Syndrome (HUS) consists ofa triad of acquired hemolytic anemia, thrombocytopenia, and renal failure that occurs acutely in otherwise healthy individuals. ", "Acute renal insufficiency in the setting of hemolysis and thrombocytopenia, a triad that constitutes adult or pediatric hemolytic uremic syndrome, can be associated with or triggered by diverse conditions such as verocytotoxin-producing Escherichia coli, viral infections, pregnancy, malignant hypertension, scleroderma, renal radiation, allograft rejection, lupus erythematosus, and assorted medications such as mitomycin C, cyclosporine, and oral contraceptives.", "Hemolytic uremic syndrome, one of the common causes of acute renal failure in children, is characterized by the triad of microangiopathy, haemolytic anemia, thrombocytopenia and acute renal failure. The diarrhoea-associated Hemolytic uremic syndrome is usually termed as a typical Hemolytic uremic syndrome." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/25011592", "http://www.ncbi.nlm.nih.gov/pubmed/24161037", "http://www.ncbi.nlm.nih.gov/pubmed/25765799", "http://www.ncbi.nlm.nih.gov/pubmed/8589282", "http://www.ncbi.nlm.nih.gov/pubmed/16387683", "http://www.ncbi.nlm.nih.gov/pubmed/20209841", "http://www.ncbi.nlm.nih.gov/pubmed/2831711", "http://www.ncbi.nlm.nih.gov/pubmed/19227723", "http://www.ncbi.nlm.nih.gov/pubmed/26265890", "http://www.ncbi.nlm.nih.gov/pubmed/17705684", "http://www.ncbi.nlm.nih.gov/pubmed/20865638", "http://www.ncbi.nlm.nih.gov/pubmed/16006690", "http://www.ncbi.nlm.nih.gov/pubmed/23380391", "http://www.ncbi.nlm.nih.gov/pubmed/25345382", "http://www.ncbi.nlm.nih.gov/pubmed/20499172", "http://www.ncbi.nlm.nih.gov/pubmed/25280590", "http://www.ncbi.nlm.nih.gov/pubmed/22956028", "http://www.ncbi.nlm.nih.gov/pubmed/24516709", "http://www.ncbi.nlm.nih.gov/pubmed/19625716", "http://www.ncbi.nlm.nih.gov/pubmed/7487540", "http://www.ncbi.nlm.nih.gov/pubmed/24548192" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D006463", "http://www.disease-ontology.org/api/metadata/DOID:12554" ]

[ "Yes." ]

[ "yes" ]

[ "Increases in blood PYY(3-36) levels were dependent on the exercise intensity (effect of session: P<0.001 by two-way ANOVA), whereas those in GLP-1 levels were similar between two different exercise sessions.", "A decrease in serum leptin levels (-48.4%, p < 0.001) was observed after intervention without changes in total peptide YY and insulin levels.", "ur data suggest that the control of spontaneous physical activity by gut hormones or their neuropeptide targets may represent an important mechanistic component of energy balance regulation", "Hunger and gut hormones remained unchanged during the bed rest.", "weight-bearing exercise has a greater exercise-induced appetite suppressive effect compared with non-weight-bearing exercise, and both forms of exercise lowered acylated ghrelin and increased total PYY, but the changes did not differ significantly between exercise modes.", "Appetite (P < 0.0005) and acylated ghrelin (P < 0.002) were suppressed during exercise but more so during SIE. Peptide YY increased during exercise but most consistently during END (P < 0.05). Acylated ghrelin was lowest in the afternoon of SIE (P = 0.018) despite elevated appetite", "Following the pre-exercise meal, ghrelin was suppressed ~17% and insulin and PYY were elevated ~157 and ~40%, respectively, relative to fasting (day 7). Following exercise, PYY, ghrelin, and GH were significantly (p < 0.0001) increased by ~11, ~16 and ~813%, respectively. The noted disruption in the typical inverse relationship between ghrelin and PYY following exercise suggests that interaction of these peptides may be at least partially responsible for post-exercise appetite suppression", "Plasma levels of PYY and GLP-1 were increased by exercise, whereas plasma ghrelin levels were unaffected by exercise", "These findings suggest ghrelin and PYY may regulate appetite during and after exercise,", "significant (P < 0.05) interaction effects for hunger, acylated ghrelin, and PYY, indicating suppressed hunger and acylated ghrelin during aerobic and resistance exercise and increased PYY during aerobic exercise", "'exercise-induced anorexia' may potentially be linked to increased PYY, GLP-1 and PP levels.", "Hunger scores and PYY, GLP-1 and PP levels showed an inverse temporal pattern during the 1-h exercise/control intervention", "Exercise significantly increased mean PYY, GLP-1 and PP levels, and this effect was maintained during the post-exercise period for GLP-1 and PP. No significant effect of exercise was observed on postprandial levels of ghrelin", "following blood donation the strenuous exercise resulted in a marked reduction in the plasma leptin", "We conclude that strenuous physical exercise; 1) fails to affect plasma leptin level but when performed after meal but not after blood withdrawal it results in an increase and fall in plasma leptin, and 2) the release of gut hormones (gastrin, CCK and PP) and stress hormones (norepinephrine, cortisol, GH) increase immediately after exercise independently of feeding or blood donation", "the unrestricted exercise group has a significantly elevated SRIF-LI concentration", "Exercise has recently been reported to influence ghrelin and PYY concentrations." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/2888163", "http://www.ncbi.nlm.nih.gov/pubmed/23402716", "http://www.ncbi.nlm.nih.gov/pubmed/18987287", "http://www.ncbi.nlm.nih.gov/pubmed/11321513", "http://www.ncbi.nlm.nih.gov/pubmed/21554896", "http://www.ncbi.nlm.nih.gov/pubmed/22619704", "http://www.ncbi.nlm.nih.gov/pubmed/19158129", "http://www.ncbi.nlm.nih.gov/pubmed/20061436", "http://www.ncbi.nlm.nih.gov/pubmed/15795476", "http://www.ncbi.nlm.nih.gov/pubmed/20690071", "http://www.ncbi.nlm.nih.gov/pubmed/23111564", "http://www.ncbi.nlm.nih.gov/pubmed/19737911", "http://www.ncbi.nlm.nih.gov/pubmed/21615652", "http://www.ncbi.nlm.nih.gov/pubmed/17470516", "http://www.ncbi.nlm.nih.gov/pubmed/21927572", "http://www.ncbi.nlm.nih.gov/pubmed/16942616" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D015444" ]

[ "The knockdown of km23-1 results in numerous effects at the cellular level, such as decreased cell migration. Additionaly, km23-1 is involved in signalling pathways and its knockdown results in decreased RhoA activation, inhibition of TGFβ-mediated activation of ERK and JNK, phosphorylation of c-Jun, transactivation of the c-Jun promoter and decreased TGFbeta responses." ]

[ "inhibition of cell migration of human colon carcinoma cells (HCCCs) in wound-healing assays", "decreased RhoA activation", "inhibition of TGFβ-mediated activation of ERK and JNK", "phosphorylation of c-Jun", "transactivation of the c-Jun promoter", "decreased key TGFbeta responses" ]

[ "Finally, our results demonstrated for the first time that depletion of km23-1 inhibited cell migration of human colon carcinoma cells (HCCCs) in wound-healing assays. Overall, our findings demonstrate that km23-1 regulates RhoA and motility-associated actin modulating proteins, suggesting that km23-1 may represent a novel target for anti-metastatic therapy.", "Further, knockdown of km23-1 inhibited TGFβ-mediated activation of ERK and JNK, phosphorylation of c-Jun, and transactivation of the c-Jun promoter.", "knockdown (KD) of km23-1 decreased RhoA activation in Mv1Lu epithelial cells", "We have previously reported that the dynein light chain (DLC) km23-1 is required for Smad2-dependent TGFbeta signaling.", "Blockade of km23-1 using a small interfering RNA approach resulted in a reduction in both total intracellular Smad2 levels and in nuclear levels of phosphorylated Smad2 after TGFbeta treatment.", "Blockade of km23 using small interfering RNAs significantly decreased key TGFbeta responses, including induction of fibronectin expression and inhibition of cell growth.", "On the other hand, inhibiting the endogenous DYNLRB1 with gene-specific small interfering RNA or pharmacologically with a specific inhibitor (vanadate) led to a significant (P < 0.05) decrease in folate uptake.", "Functional studies showed that some mutations disrupt km23 function, resulting in aberrant transforming growth factor-beta signaling and presumably enhanced tumorigenicity." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/15925487", "http://www.ncbi.nlm.nih.gov/pubmed/19711352", "http://www.ncbi.nlm.nih.gov/pubmed/23079622", "http://www.ncbi.nlm.nih.gov/pubmed/22637579", "http://www.ncbi.nlm.nih.gov/pubmed/17420258", "http://www.ncbi.nlm.nih.gov/pubmed/16778097", "http://www.ncbi.nlm.nih.gov/pubmed/19571232" ]

[ { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#subject", "s": "http://linkedlifedata.com/resource/#_41324156523900B", "o": "http://linkedlifedata.com/resource/#_41324156523900A" } ]

[ "http://www.uniprot.org/uniprot/DLRB1_HUMAN" ]

[ "Multicenter Randomized CLinical trial of Endovascular treatment for Acute ischemic stroke in the Netherlands (MR CLEAN) study investigated endovascular treatment for acute ischemic stroke." ]

[ "acute ischemic stroke" ]

[ "INTRODUCTION: A recent randomized controlled trial (RCT), the Multicenter Randomized CLinical trial of Endovascular treatment for Acute ischemic stroke in the Netherlands (MR CLEAN), demonstrated better outcomes with endovascular treatment compared with medical therapy for acute ischemic stroke (AIS). ", "INTRODUCTION: A recent randomized controlled trial (RCT), the Multicenter Randomized CLinical trial of Endovascular treatment for Acute ischemic stroke in the Netherlands (MR CLEAN), demonstrated better outcomes with endovascular treatment compared with medical therapy for acute ischemic stroke (AIS).", "CONCLUSIONS: In patients with acute ischemic stroke caused by a proximal intracranial occlusion of the anterior circulation, intraarterial treatment administered within 6 hours after stroke onset was effective and safe. (Funded by the Dutch Heart Foundation and others; MR CLEAN Netherlands Trial Registry number, NTR1804, and Current Controlled Trials number, ISRCTN10888758.).", "MR CLEAN, a multicenter randomized clinical trial of endovascular treatment for acute ischemic stroke in the Netherlands: study protocol for a randomized controlled trial.", " In our view, a rational and ethical approach would now be to treat quickly with IV rtPA and when possible, refer and include in new randomized clinical trials that compare intra-arterial treatment with standard care, such as MR CLEAN or BASICS in the Netherlands." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/25517348", "http://www.ncbi.nlm.nih.gov/pubmed/25432979", "http://www.ncbi.nlm.nih.gov/pubmed/25179366", "http://www.ncbi.nlm.nih.gov/pubmed/24330796" ]

[]

[]

[ "Nanog, Pou5f1 and SoxB1 activate zygotic gene expression during the maternal-to-zygotic transition. Maternal Nanog, Pou5f1 and SoxB1 are required to initiate the zygotic developmental program and induce clearance of the maternal program by activating miR-430 expression." ]

[ "Nanog", "Pou5f1", "SoxB1" ]

[ "Nanog, Pou5f1 and SoxB1 activate zygotic gene expression during the maternal-to-zygotic transition.", "Our results demonstrate that maternal Nanog, Pou5f1 and SoxB1 are required to initiate the zygotic developmental program and induce clearance of the maternal program by activating miR-430 expression.", "Here we show that Nanog, Pou5f1 (also called Oct4) and SoxB1 regulate zygotic gene activation in zebrafish.", "Here we show that Nanog, Pou5f1 (also called Oct4) and SoxB1 regulate zygotic gene activation in zebrafish. We identified several hundred genes directly activated by maternal factors, constituting the first wave of zygotic transcription." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/24056933" ]

[ { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A0134867", "o": "D015027" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A2030872", "o": "D015027" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A0062415", "o": "D015870" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A0057285", "o": "D015870" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A0057283", "o": "D015870" } ]

[ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D015027", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D018507", "http://amigo.geneontology.org/amigo/term/GO:0010468", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D020869", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005786", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D015870" ]

[ "Yes, irritable bowel syndrome (IBS) is more common in women with endometriosis. It has been shown that 15% of the patients with endometriosis also had IBS. Women with endometriosis are more likely to have received a diagnosis of IBS. Endometriosis may coexist with or be misdiagnosed as IBS." ]

[ "yes" ]

[ "CONCLUSIONS: Comorbid pain syndromes, mood conditions and asthma are common in adolescents and young women with endometriosis.", "There are many etiologies of pelvic pain that present with symptoms resembling those of endometriosis-associated pelvic pain that are not diagnosable with laparoscopy, such as interstitial cystitis and irritable bowel syndrome.", "Often, such patients are labelled with irritable bowel syndrome. ", "Irritable bowel syndrome (IBS) is also common in this setting, and it was speculated that the visceral hypersensitivity associated with this condition might be amplifying the symptoms of endometriosis. ", "RESULTS: Compared with controls, patients with minimal to mild and moderate to severe endometriosis had a higher prevalence of symptoms consistent with IBS (0% vs 65% and 50%, respectively, p<0.001) with significantly lower mean pain thresholds (39.5 mm Hg (95% CI 36.0 to 43.0) vs 28.1 mm Hg (95% CI 24.5 to 31.6), p=0.001 and 28.8 mm Hg (95% CI 24.9 to 32.6), p=0.002) not explained by differences in rectal compliance. ", "Similarly, women with a history of irritable bowel syndrome were twice as likely to develop endometriosis [AOR=1.9, 95% CI (1.03-3.87)].", "A weak association between reported family history of endometriosis and history of irritable bowel syndrome and the development of endometriosis was also observed. ", "Irritable bowel syndrome and chronic constipation in patients with endometriosis.", "Fifteen per cent of the patients with endometriosis also had IBS and 14% of the patients with endometriosis had functional constipation without IBS.", "CONCLUSION: In patients with endometriosis, 29% also had IBS or constipation. ", "Seventy-six women (21.4%) had previously been diagnosed with irritable bowel syndrome and 79% of them had endometriosis confirmed.", "Compared with controls, women with endometriosis had increased risks of abdominopelvic pain (OR 5.2 [95% CI: 4.7-5.7]), dysmenorrhoea (OR 8.1 [95% CI: 7.2-9.3]), menorrhagia (OR 4.0 [95% CI: 3.5-4.5]), subfertility (OR 8.2 [95% CI: 6.9-9.9]), dyspareunia and/or postcoital bleeding (OR 6.8 [95% CI: 5.7-8.2]), and ovarian cysts (OR 7.3 [95% CI: 5.7-9.4]), and of being diagnosed with irritable bowel syndrome (IBS) (OR 1.6 [95% CI: 1.3-1.8]) or pelvic inflammatory disease (OR 3.0 [95% CI: 2.5-3.6]).", "Endometriosis may coexist with or be misdiagnosed as pelvic inflammatory disease or IBS.", "RESULTS: Compared with the controls, women with endometriosis were 3.5 times more likely to have received a diagnosis of IBS (OR 3.5 [95% CI: 3.1-3.9]). Even after women had been diagnosed with endometriosis, they were still two and a half times more likely to receive a new diagnosis of IBS when compared with the controls (OR 2.5 [95% CI: 2.2-2.8]).", "CONCLUSIONS: Women with endometriosis are more likely to be diagnosed with IBS and PID than controls, even after a definitive diagnosis of endometriosis has been reached.", "In women, clinical studies suggest that functional pain syndromes such as irritable bowel syndrome, interstitial cystitis, and fibromyalgia, are co-morbid with endometriosis, chronic pelvic pain, and others diseases.", "In women, clinical studies suggest that pain syndromes such as irritable bowel syndrome and interstitial cystitis, which are associated with visceral hyperalgesia, are often comorbid with endometriosis and chronic pelvic pain. ", "Depression, anxiety, IBS, FM, CFS, and IC were more common in migraine with EM group than in controls.", "Intestinal endometriosis can mimic many gastrointestinal diseases, such as irritable bowel syndrome, inflammatory bowel disease, infections and neoplasms.", "Endometriosis is often associated with other painful conditions such as irritable bowel syndrome, interstitial cystitis and fibromyalgia. ", "CONCLUSIONS: Diagnosis of endometriosis should be considered in women with recurrent monthly abdominal pain and bowel symptoms, especially if accompanied by gynaecologic complaints, even because the significant symptoms overlap with the irritable bowel syndrome (IBS) and makes the differentiation extremely difficult.", "Intestinal endometriosis is typically asymptomatic; however, when symptoms occur, they can mimic those of irritable bowel syndrome.", " Similarly, women with a history of irritable bowel syndrome were twice as likely to develop endometriosis [AOR=1.", "Irritable bowel syndrome (IBS) is also common in this setting, and it was speculated that the visceral hypersensitivity associated with this condition might be amplifying the symptoms of endometriosis.", "Irritable bowel syndrome (IBS) is also common in this setting, and it was speculated that the visceral hypersensitivity associated with this condition might be amplifying the symptoms of endometriosis." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/15341718", "http://www.ncbi.nlm.nih.gov/pubmed/18478547", "http://www.ncbi.nlm.nih.gov/pubmed/14501624", "http://www.ncbi.nlm.nih.gov/pubmed/15605531", "http://www.ncbi.nlm.nih.gov/pubmed/21527837", "http://www.ncbi.nlm.nih.gov/pubmed/22096721", "http://www.ncbi.nlm.nih.gov/pubmed/18646315", "http://www.ncbi.nlm.nih.gov/pubmed/21868492", "http://www.ncbi.nlm.nih.gov/pubmed/23507008", "http://www.ncbi.nlm.nih.gov/pubmed/15894210", "http://www.ncbi.nlm.nih.gov/pubmed/19694698", "http://www.ncbi.nlm.nih.gov/pubmed/18715239", "http://www.ncbi.nlm.nih.gov/pubmed/17635599", "http://www.ncbi.nlm.nih.gov/pubmed/17701798", "http://www.ncbi.nlm.nih.gov/pubmed/19832874", "http://www.ncbi.nlm.nih.gov/pubmed/18715240", "http://www.ncbi.nlm.nih.gov/pubmed/22134016", "http://www.ncbi.nlm.nih.gov/pubmed/17493437" ]

[]

[ "http://www.disease-ontology.org/api/metadata/DOID:289", "http://www.disease-ontology.org/api/metadata/DOID:9778" ]

[ "The European Organisation for Research and Treatment of Cancer Quality of Life Group information questionnaire (EORTC QLQ-INFO 25) evaluates the level of information patients have received in different areas of their disease, treatment and care, and evaluates qualitative aspects together with satisfaction with information." ]

[]

[ "The EORTC QLQ-INFO25 was used to evaluate the perceived level of and satisfaction with information. ", "METHODS: The EORTC information questionnaire, EORTC QLQ-INFO25, was administered during the treatment process.", "The EORTC information questionnaire, EORTC QLQ-INFO25. Validation study for Spanish patients.", "INTRODUCTION: The EORTC QLQ-INFO25 evaluates the information received by cancer patients. ", "Information disclosure to cancer patients: EORTC QLQ-INFO25 questionnaire.", "We highlight the need to assess patients' characteristics and desires through questionnaires and interviews and present the European Organisation for Research and Treatment of Cancer Quality of Life Group information questionnaire (EORTC QLQ-INFO 25). This instrument evaluates the level of information patients have received in different areas of their disease, treatment and care, and evaluates qualitative aspects. ", "AIM: The EORTC Quality of Life (QOL) Group has developed an instrument to evaluate the information received by cancer patients. This study assessed the psychometric characteristics of the EORTC INFO module in a large international/multi-cultural sample of cancer patients. ", "An international validation study of the EORTC QLQ-INFO25 questionnaire: an instrument to assess the information given to cancer patients.", "The EORTC QLQ-INFO25 was used to evaluate the perceived level of and satisfaction with information.", "The EORTC QLQ-INFO25 evaluates the information received by cancer patients", "The EORTC QLQ-INFO25 was used to evaluate the perceived level of and satisfaction with information" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/21680301", "http://www.ncbi.nlm.nih.gov/pubmed/24834120", "http://www.ncbi.nlm.nih.gov/pubmed/25475735", "http://www.ncbi.nlm.nih.gov/pubmed/21671697", "http://www.ncbi.nlm.nih.gov/pubmed/22052786", "http://www.ncbi.nlm.nih.gov/pubmed/20674333", "http://www.ncbi.nlm.nih.gov/pubmed/22638756" ]

[]

[]

[ "BNP and NTproBNP increase early after exercise in healthy athletes performing different types of sports. It is unknown the reason of this increase. The transient increases in BNP, NT-pro-BNP and troponin T are more likely to reflect myocardial stunning than cardiomyocyte damage." ]

[ "yes" ]

[ "NT-pro-BNP was significantly elevated postexercise in both adults and adolescents and remained above baseline at 24 h in both groups.", "NT-pro-BNP concentrations increased significantly (28 +/- 17.1 vs 795 +/- 823 ng x L, P < 0.05), whereas postrace cTnT were elevated in just five athletes (20%).", "[NT-pro-BNP] was observed immediately after the marathon (median [NT-pro-BNP] before: 39.6 pg ml(-1), after: 138.6 pg ml(-1), p=0.003) with a further increase on day one. [BNP] did not increase immediately after the marathon but increased on day one (median [BNP] before: 15 pg ml(-1), day one: 27.35 pg ml(-1), p=0.006).", "Pro-BNP was significantly increased immediately post-race (27+/-21 vs 7+/-2 pmol/L pre-race, P < or = 0.007), which 12-24 h later, decreased to 19+/-14 pmol/L (P = 0.07 vs pre-race).", "The relatively high NT-proBNP levels after active recovery when psychophysical stress is higher, because of cycling and cold water immersion, suggest that not only endurance exercise, but also strenuous, stressful short exercise can induce an increase in NT-proBNP concentrations.", "Running a marathon significantly increases NT-pro-BNP levels in healthy adults. This increase could be partially attributed to cardiac stress.", "Increases in NT-proBNP can be found in a major part of obviously healthy athletes after prolonged strenuous exercise. The release of BNP during and after exercise may not result from myocardial damage but may have cytoprotective and growth-regulating effects. The different nature of exercise-induced increases in BNP and cardiac troponins has to be elucidated in the future.", "In healthy cyclists, transient increases in NT-pro-BNP and cTnT are more likely to reflect cardiac fatigue than injury.", "The rise in BNP in older athletes may reflect a reversible, mainly diastolic left ventricular dysfunction. ", "Plasma BNP concentrations were higher in both the judo and marathon groups than in controls, and positively correlated with LV mass as well as with deceleration time.", "Such exercise significantly increased ANP and BNP levels in healthy men, and the increases could be partially attributed to myocardial damage during the race." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/16338248", "http://www.ncbi.nlm.nih.gov/pubmed/22653984", "http://www.ncbi.nlm.nih.gov/pubmed/16125505", "http://www.ncbi.nlm.nih.gov/pubmed/17289431", "http://www.ncbi.nlm.nih.gov/pubmed/19092706", "http://www.ncbi.nlm.nih.gov/pubmed/14523304", "http://www.ncbi.nlm.nih.gov/pubmed/12417808", "http://www.ncbi.nlm.nih.gov/pubmed/16879068", "http://www.ncbi.nlm.nih.gov/pubmed/18076361", "http://www.ncbi.nlm.nih.gov/pubmed/17395308", "http://www.ncbi.nlm.nih.gov/pubmed/11320362", "http://www.ncbi.nlm.nih.gov/pubmed/23304255", "http://www.ncbi.nlm.nih.gov/pubmed/18630737", "http://www.ncbi.nlm.nih.gov/pubmed/18248532", "http://www.ncbi.nlm.nih.gov/pubmed/18184752", "http://www.ncbi.nlm.nih.gov/pubmed/12890912", "http://www.ncbi.nlm.nih.gov/pubmed/16446686", "http://www.ncbi.nlm.nih.gov/pubmed/19638823" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D054874", "http://www.uniprot.org/uniprot/ANFB_OREMO", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D056352", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D015444", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D020097", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013177" ]

[ "The association between hormone replacement therapy and meningioma risk is controversial. Increased risk of meningioma was demonstrated in estrogen-only hormonal replacement therapy. However, other studies did not find an association between hormonal replacement therapy and meningioma risk." ]

[]

[ "The meta-analyses yielded significantly increased risks for all CNS tumors, glioma and meningioma in users of estrogen-only [1.35 (1.22-1.49), 1.23 (1.06-1.42) and 1.31 (1.20-1.43), respectively] but not estrogen-progestin HT [1.09 (0.99-1.19), 0.92 (0.78-1.08) and 1.05 (0.95-1.16), respectively]; these differences were statistically significant (p<0.005 for each tumor type). There was no significant difference between glioma and meningioma risk in users of estrogen-only HT. The totality of the available evidence suggests an increased risk of all CNS tumors (and of glioma and meningioma separately) in users of estrogen-only HT. ", "Among premenopausal women, current use of oral contraceptives was associated with an increased risk of meningiomas (OR 1.8, 95% CI 1.1-2.9), while current use of hormone replacement therapy among postmenopausal women was not associated with a significant elevation in risk (OR 1.1, 95% CI 0.74-1.67). ", "The relationship between current use of exogenous hormones and meningioma remains unclear, limited by the small numbers of patients currently on oral hormone medications and a lack of hormone receptor data for meningioma tumors.", "Ever use of estradiol-only therapy was associated with an increased risk of meningioma (standardized incidence ratio = 1.29, 95% confidence interval: 1.15, 1.44). Among women who had been using estradiol-only therapy for at least 3 years, the incidence of meningioma was 1.40-fold higher (95% confidence interval: 1.18, 1.64; P<0.001) than in the background population. ", "Estradiol-only therapy was accompanied with a slightly increased risk of meningioma.", "Results from several prospective, large-scale studies indicate that postmenopausal hormone therapy may increase the risk for diagnosing meningioma by 30-80%, but there is no effect in regard to glioma. ", "A retrospective study including more than 350,000 women, about 1400 of whom had developed meningioma, showed that the risk of meningioma was about twice as high in users of postmenopausal hormone replacement therapy as in non-users.", "Compared with never users of HRT, the relative risks (RRs) for all incident CNS tumours, gliomas, meningiomas and acoustic neuromas in current users of HRT were 1.20 (95% CI: 1.05-1.36), 1.09 (95% CI: 0.89-1.32), 1.34 (95% CI: 1.03-1.75) and 1.58 (95% CI: 1.02-2.45), respectively, and there was no significant difference in the relative risks by tumour type (heterogeneity p = 0.2). ", "BACKGROUND: Previous studies on association of exogenous female sex hormones and risk for meningioma have yielded conflicting results.", "RESULTS: Postmenopausal hormonal treatment, use of contraceptives, or fertility treatment did not influence the risk of meningioma. ", "CONCLUSIONS: Overall, we found little indication that reproductive factors or use of exogenous sex hormones affect meningioma risk.", "Although not definitive, available data suggest an association between the use of hormone replacement therapy and increased meningioma risk. ", "BACKGROUND: The role of exogenous hormone exposures in the development of meningioma is unclear, but these exposures have been proposed as one hypothesis to explain the over-abundance of such tumors in women.", "RESULTS: Although risk of meningioma appeared modestly elevated in past OC users (OR = 1.5, 95% CI 0.8 - 2.7), and in current users (OR = 2.5, 95% CI 0.5 - 12.6), the confidence intervals were wide. ", "Likewise, risk of meningioma was only weakly associated with past use of HRT (OR = 0.7, 95% CI 0.4 - 1.3), and not at all with current use of HRT (OR = 1.0, 95% CI 0.5 - 2.2). ", " Overall, in post menopausal women, HRT use appeared to confer a non-significant protective effect, and was not associated with low or high PR expressing meningiomas.CONCLUSION: This study found little evidence of associations between meningioma and exogenous hormone exposures in women but did suggest that some hormonal exposures may influence tumor biology in those women who develop meningioma.", "The increased odds ratios with African Americans was retained in post-menopausal women, while the protective odds ratios for pregnancy, smoking and oral contraceptives (OCs) became stronger in pre-menopausal women. The pattern by duration and timing of use does not suggest an etiologic role for OCs or hormone replacement therapy. ", "The use of hormone replacement therapy in symptomatic postmenopausal women either with previously treated disease or with dormant tumors is discussed, but remains controversial.", "Although not definitive, available data suggest an association between the use of hormone replacement therapy and increased meningioma risk.", "OC use was associated with increased risk of a meningioma expressing less rather than more PR (OR = 3.2, 95% CI 1.3 - 8.0). ", "In further analysis by hormone receptor status, there was some indication for an increased risk of progesterone receptor-positive meningiomas associated with oral contraceptive use (OR 1.39, 95% confidence interval 0.92-2.10) and other hormonal contraception (OR 1.50, 95% CI 0.95-2.36). ", "Several studies indicate that use of hormone replacement therapy (HRT) is associated with an increased risk of intracranial meningioma, while associations between HRT use and risk of other brain tumors have been less explored.", "available data suggest an association between the use of hormone replacement therapy and increased meningioma risk.", "A significant positive association existed between meningioma risk and increased body mass index (p &lt; 0.01) while a significant negative association existed between meningioma risk and current smoking (p &lt; 0.01). Among premenopausal women, current use of oral contraceptives was associated with an increased risk of meningiomas (OR 1.8, 95% CI 1.1-2.9), while current use of hormone replacement therapy among postmenopausal women was not associated with a significant elevation in risk (OR 1.1, 95% CI 0.74-1.67).", "A higher risk of meningioma was observed among postmenopausal women who were current users of hormone replacement therapy (HR,", "Among premenopausal women, current use of oral contraceptives was associated with an increased risk of meningiomas (OR 1.8, 95% CI 1.1-2.9), while current use of hormone replacement therapy among postmenopausal women was not associated with a significant elevation in risk (OR 1.1, 95% CI 0.74-1.67). There was no association between use of fertility medications and meningioma risk.", "Although not definitive, available data suggest an association between the use of hormone replacement therapy and increased meningioma risk.", "A higher risk of meningioma was observed among postmenopausal women who were current users of hormone replacement therapy (HR, 1.79; 95% CI, 1.18-2.71) compared with never users.", "Among premenopausal women, current use of oral contraceptives was associated with an increased risk of meningiomas (OR 1.8, 95% CI 1.1-2.9), while current use of hormone replacement therapy among postmenopausal women was not associated with a significant elevation in risk (OR 1.1, 95% CI 0.74-1.67)." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/16570277", "http://www.ncbi.nlm.nih.gov/pubmed/22287638", "http://www.ncbi.nlm.nih.gov/pubmed/21067422", "http://www.ncbi.nlm.nih.gov/pubmed/20730482", "http://www.ncbi.nlm.nih.gov/pubmed/15006250", "http://www.ncbi.nlm.nih.gov/pubmed/24138870", "http://www.ncbi.nlm.nih.gov/pubmed/20738039", "http://www.ncbi.nlm.nih.gov/pubmed/20091865", "http://www.ncbi.nlm.nih.gov/pubmed/20802020", "http://www.ncbi.nlm.nih.gov/pubmed/17580362", "http://www.ncbi.nlm.nih.gov/pubmed/23101448", "http://www.ncbi.nlm.nih.gov/pubmed/16759391", "http://www.ncbi.nlm.nih.gov/pubmed/25335165" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D015914", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D008579", "http://www.disease-ontology.org/api/metadata/DOID:3565" ]

[ "Results suggest the potential value of self-management for chronic pain patients and the potential acceptability of web-based delivery of intervention content. ", "Yes, there are successful web based self management strategies for chronic pain." ]

[ "yes" ]

[ "Fibromyalgia Symptom Reduction by Online Behavioral Self-monitoring, ", "This study aimed to evaluate effects of a web-based, self-monitoring and symptom management system (SMARTLog) that analyzes personal self-monitoring data and delivers data-based feedback over time.", "Moderate use (3 times weekly x 3 months) increased likelihood of clinically significant improvements in pain, memory, gastrointestinal problems, depression, fatigue, and concentration; heavy use (4.5 times weekly x five months) produced the above plus improvement in stiffness and sleep difficulties.", "Results suggest that the tailored online chronic pain management program showed promising effects on pain at 1 and 6 months posttreatment and quality of life at 6 months posttreatment in this naturalistic study.", "Results suggest the potential value of self-management for chronic pain patients and the potential acceptability of web-based delivery of intervention content.", "Patient involvement can be fostered by web-based applications combining health information with decision support or behaviour change support. These so-called Interactive Health Communication Applications (IHCAs) can reach great numbers of patients at low financial cost and provide information and support at the time, place and learning speed patients prefer.", "Web-based interventions may also be effective in enhancing self-management for individuals with chronic pain, but little is known about long-term effects. Research on Web-based interventions to support self-management following participation in pain management programs is limited. OBJECTIVE: The aim is to examine the long-term effects of a 4-week smartphone-intervention " ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/24251273", "http://www.ncbi.nlm.nih.gov/pubmed/23859438", "http://www.ncbi.nlm.nih.gov/pubmed/23768119", "http://www.ncbi.nlm.nih.gov/pubmed/23538392", "http://www.ncbi.nlm.nih.gov/pubmed/24067267" ]

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[ "Overgrowth conditions are a heterogeneous group of disorders characterised by increased growth and variable features, including macrocephaly, distinctive facial appearance and various degrees of learning difficulties and intellectual disability. Among them, Sotos and Weaver syndromes are clinically well defined and due to heterozygous mutations in NSD1 and EZH2, respectively. NSD1 and EZH2 are both histone-modifying enzymes", "Constitutional NSD1 and EZH2 mutations cause Sotos and Weaver syndromes respectively, overgrowth syndromes with considerable phenotypic overlap. NSD1 and EZH2 are SET domain-containing histone methyltransferases that play key roles in the regulation of transcription through histone modification and chromatin modeling." ]

[ "yes" ]

[ "Overgrowth conditions are a heterogeneous group of disorders characterised by increased growth and variable features, including macrocephaly, distinctive facial appearance and various degrees of learning difficulties and intellectual disability. Among them, Sotos and Weaver syndromes are clinically well defined and due to heterozygous mutations in NSD1 and EZH2, respectively. NSD1 and EZH2 are both histone-modifying enzymes", "NSD1 and EZH2 are SET domain-containing histone methyltransferases that play key roles in the regulation of transcription through histone modification and chromatin modeling: NSD1 preferentially methylates lysine residue 36 of histone 3 (H3K36) and is primarily associated with active transcription, while EZH2 shows specificity for lysine residue 27 (H3K27) and is associated with transcriptional repression", "Constitutional NSD1 and EZH2 mutations cause Sotos and Weaver syndromes respectively, overgrowth syndromes with considerable phenotypic overlap", "Clinically, Weaver syndrome is closely related to Sotos syndrome, which is frequently caused by mutations in NSD1", "Overgrowth syndromes such as Beckwith-Wiedemann syndrome, Sotos syndrome, and Weaver syndrome have an increased risk of neoplasia.", "Thus, it is not surprising that prenatal overgrowth occurs in several syndromes, including the Sotos and Weaver syndromes.", "NSD1 mutations are the major cause of Sotos syndrome and occur in some cases of Weaver syndrome but are rare in other overgrowth phenotypes.", "We conclude therefore that NSD1 mutations account for most cases of Sotos syndrome and a significant number of Weaver syndrome cases in our series.", "We conclude that intragenic mutations of NSD1 are the major cause of Sotos syndrome and account for some Weaver syndrome cases but rarely occur in other childhood overgrowth phenotypes.", "Overgrowth syndromes such as Beckwith-Wiedemann syndrome, Sotos syndrome, and Weaver syndrome have an increased risk of neoplasia", "NSD1 mutations are the major cause of Sotos syndrome and occur in some cases of Weaver syndrome but are rare in other overgrowth phenotypes", "We conclude that intragenic mutations of NSD1 are the major cause of Sotos syndrome and account for some Weaver syndrome cases but rarely occur in other childhood overgrowth phenotypes", "Considerable phenotypic overlap between Sotos and Weaver syndromes is also evident. ", "Considerable phenotypic overlap between Sotos and Weaver syndromes is also evident. The identification of an EZH2 mutation can therefore provide an objective means of confirming a subtle presentation of Weaver syndrome and/or distinguishing Weaver and Sotos syndromes.", " Overgrowth syndromes such as Beckwith-Wiedemann syndrome, Sotos syndrome, and Weaver syndrome have an increased risk of neoplasia. Two previous cases of neuroblastoma have been reported in children with Weaver syndrome.", "Weaver syndrome is closely related to Sotos syndrome,", "Overgrowth syndromes such as Beckwith-Wiedemann syndrome, Sotos syndrome, and Weaver syndrome have an increased risk of neoplasia.", "Considerable phenotypic overlap between Sotos and Weaver syndromes is also evident.", "Clinically, Weaver syndrome is closely related to Sotos syndrome, which is frequently caused by mutations in NSD1." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/9781911", "http://www.ncbi.nlm.nih.gov/pubmed/12807965", "http://www.ncbi.nlm.nih.gov/pubmed/23592277", "http://www.ncbi.nlm.nih.gov/pubmed/12464997", "http://www.ncbi.nlm.nih.gov/pubmed/22287508", "http://www.ncbi.nlm.nih.gov/pubmed/19011474", "http://www.ncbi.nlm.nih.gov/pubmed/24852293", "http://www.ncbi.nlm.nih.gov/pubmed/24214728" ]

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[ "Evolocumab (AMG145) is a fully human monoclonal antibody to proprotein convertase subtilisin/kexin type 9 (PCSK9) that demonstrated marked reductions in plasma low-density lipoprotein cholesterol concentrations in statin-intolerant patients." ]

[ "proprotein convertase subtilisin/kexin type 9" ]

[ "Efficacy and safety profile of evolocumab (AMG145), an injectable inhibitor of the proprotein convertase subtilisin/kexin type 9: the available clinical evidence.", "AREAS COVERED: Evolocumab (AMG145) is a monoclonal antibody inhibiting the proprotein convertase subtilisin/kexin type 9 that binds to the liver LDL receptor and prevents it from normal recycling by targeting it for degradation. ", "Efficacy and safety of evolocumab (AMG 145), a fully human monoclonal antibody to PCSK9, in hyperlipidaemic patients on various background lipid therapies: pooled analysis of 1359 patients in four phase 2 trials.", "We report a pooled analysis from four phase 2 studies of evolocumab (AMG 145), a monoclonal antibody to PCSK9. ", "Reduction in lipoprotein(a) with PCSK9 monoclonal antibody evolocumab (AMG 145): a pooled analysis of more than 1,300 patients in 4 phase II trials.", "METHODS: A pooled analysis of data from 1,359 patients in 4 phase II trials assessed the effects of evolocumab, a fully human monoclonal antibody to PCSK9, on Lp(a), the relationship between Lp(a) and lowering of low-density lipoprotein cholesterol (LDL-C) and apolipoprotein B, and the influence of background statin therapy.", "CONCLUSIONS: Inhibition of PCSK9 with evolocumab resulted in significant dose-related reductions in Lp(a). ", "Monoclonal antibodies that inhibit proprotein convertase subtilisin/kexin type 9, including evolocumab (previously AMG 145), dramatically lowered LDL-C in phase 2 clinical trials when administered alone or in combination with a statin. ", "Evolocumab (AMG 145) is a fully human monoclonal antibody that binds PCSK9, inhibiting its interaction with the LDL receptor to preserve LDL-receptor recycling and reduce LDL-C.", "Antibody therapeutics in Phase 3 studies are described, with an emphasis on those with study completion dates in 2014, including antibodies targeting interleukin-17a or the interleukin-17a receptor (secukinumab, ixekizumab, brodalumab), proprotein convertase subtilisin/kexin type 9 (alirocumab, evolocumab, bococizumab), and programmed death 1 receptor (lambrolizumab, nivolumab).", "BACKGROUND: Evolocumab (AMG 145), a monoclonal antibody against proprotein convertase subtilisin/kexin type 9 (PCSK9), significantly reduced low-density lipoprotein cholesterol (LDL-C) in phase 2 studies of 12 weeks' duration. ", "These compounds act either by reducing low-density lipoprotein (LDL) production by inhibiting apolipoprotein B synthesis with an antisense oligonucleotide (mipomersen) or by inhibiting microsomal triglyceride transfer protein (lomitapide), or by enhancing LDL catabolism via monoclonal antibody-mediated inhibition of the activity of proprotein convertase subtilisin/kexin 9 (PCSK9) (evolocumab). ", "Inhibition of PCSK9 with evolocumab in homozygous familial hypercholesterolaemia (TESLA Part B): a randomised, double-blind, placebo-controlled trial.", "Evolocumab, a monoclonal antibody to proprotein convertase subtilisin/kexin type 9 (PCSK9), reduced LDL cholesterol by 16% in a pilot study. ", "PCSK9 inhibition with evolocumab (AMG 145) in heterozygous familial hypercholesterolaemia (RUTHERFORD-2): a randomised, double-blind, placebo-controlled trial.", "We investigated the effect of PCSK9 inhibition with evolocumab (AMG 145) on LDL cholesterol in patients with this disorder. ", "Some of the anti-dyslipidemic drugs which work by PCSK9 inhibition include evolocumab, alirocumab and ALN-PCS.", "We highlight the different steps of this adventure and review the published clinical trials especially those with the anti-PCSK9 antibodies evolocumab (AMG 145) and alirocumab (SAR236553/REGN727), which are in phase III trials.", "Monoclonal antibodies against PCSK9 represent so far the most advanced approach in clinical development, with alirocumab, evolocumab and bococizumab under advanced clinical development. ", "AREAS COVERED: Evolocumab and alirocumab are fully human monoclonal antibodies inhibiting the proprotein convertase subtilisin/kexin type 9 (PCSK9) that binds to hepatic LDL receptor and prevents it from normal recycling by targeting it for degradation.", "Phase II (for evolocumab and alirocumab) and III (for evolocumab) trials show that PCSK9 inhibitors are equally well tolerated, with adverse events mainly limited to mild-to-moderate nasopharyngitis, injection-site pain, arthralgia and back pain. ", "Four classes of newer lipid-lowering drugs offer promising advances in treating FH, namely the apolipoprotein-B synthesis inhibitors (mipomersen), the microsomal transfer protein inhibitors (lomitapide), the cholesterol ester transfer protein inhibitors (anacetrapib, evacetrapib) and the proprotein convertase subtilisin/kexin type 9 inhibitors (evolocumab, alirocumab).", "Monoclonal antibodies that inhibit proprotein convertase subtilisin/ kexin type 9 (PCSK9), which degrades the LDL receptor, like alirocumab and evolocumab, are in phase 3 trials.", "In support of the drug development program for Evolocumab, a fully human IgG₂ antibody that targets PCSK9, a quantitative ELISA to measure free PCSK9 in human serum was developed. ", "IMPORTANCE: In phase 2 studies, evolocumab, a fully human monoclonal antibody to PCSK9, reduced LDL-C levels in patients receiving statin therapy. ", "Anti-PCSK9 antibody effectively lowers cholesterol in patients with statin intolerance: the GAUSS-2 randomized, placebo-controlled phase 3 clinical trial of evolocumab.", "Evolocumab, a fully human monoclonal antibody to proprotein convertase subtilisin/kexin type 9 (PCSK9), demonstrated marked reductions in plasma low-density lipoprotein cholesterol (LDL-C) in a phase 2 study in statin-intolerant patients.", "Anti-PCSK9 monotherapy for hypercholesterolemia: the MENDEL-2 randomized, controlled phase III clinical trial of evolocumab.", "BACKGROUND: Evolocumab, a fully human monoclonal antibody against proprotein convertase subtilisin/kexin type 9 (PCSK9), significantly reduced LDL-C in phase II trials. ", "BACKGROUND: Evolocumab, a monoclonal antibody that inhibits proprotein convertase subtilisin/kexin type 9 (PCSK9), significantly reduced low-density lipoprotein (LDL) cholesterol levels in phase 2 studies. ", "Effects of evolocumab (AMG 145), a monoclonal antibody to PCSK9, in hypercholesterolemic, statin-treated Japanese patients at high cardiovascular risk--primary results from the phase 2 YUKAWA study." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/24691094", "http://www.ncbi.nlm.nih.gov/pubmed/25410046", "http://www.ncbi.nlm.nih.gov/pubmed/25052769", "http://www.ncbi.nlm.nih.gov/pubmed/24661068", "http://www.ncbi.nlm.nih.gov/pubmed/24477778", "http://www.ncbi.nlm.nih.gov/pubmed/25079474", "http://www.ncbi.nlm.nih.gov/pubmed/24662398", "http://www.ncbi.nlm.nih.gov/pubmed/25470376", "http://www.ncbi.nlm.nih.gov/pubmed/24694531", "http://www.ncbi.nlm.nih.gov/pubmed/24961142", "http://www.ncbi.nlm.nih.gov/pubmed/24481874", "http://www.ncbi.nlm.nih.gov/pubmed/24373748", "http://www.ncbi.nlm.nih.gov/pubmed/25282520", "http://www.ncbi.nlm.nih.gov/pubmed/24953393", "http://www.ncbi.nlm.nih.gov/pubmed/24953396", "http://www.ncbi.nlm.nih.gov/pubmed/25002170", "http://www.ncbi.nlm.nih.gov/pubmed/24859266", "http://www.ncbi.nlm.nih.gov/pubmed/24678979", "http://www.ncbi.nlm.nih.gov/pubmed/25282519", "http://www.ncbi.nlm.nih.gov/pubmed/24255061", "http://www.ncbi.nlm.nih.gov/pubmed/24509273", "http://www.ncbi.nlm.nih.gov/pubmed/24284914", "http://www.ncbi.nlm.nih.gov/pubmed/24598985", "http://www.ncbi.nlm.nih.gov/pubmed/24825642" ]

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[ "Yes. Especially, a large fraction of non-exonic UCEs is transcribed across all developmental stages examined from only one DNA strand." ]

[ "yes" ]

[ "Starting from a genome-wide expression profiling, we demonstrate for the first time a functional link between oxygen deprivation and the modulation of long noncoding transcripts from ultraconserved regions, termed transcribed-ultraconserved regions (T-UCRs)", "Our data gives a first glimpse of a novel functional hypoxic network comprising protein-coding transcripts and noncoding RNAs (ncRNAs) from the T-UCRs category", "Highly conserved elements discovered in vertebrates are present in non-syntenic loci of tunicates, act as enhancers and can be transcribed during development", "The majority of these regions map onto ultraconserved elements and we demonstrate that they can act as functional enhancers within the organism of origin, as well as in cross-transgenesis experiments, and that they are transcribed in extant species of Olfactores. We refer to the elements as 'Olfactores conserved non-coding elements'", "We used a custom microarray to assess the levels of UCE transcription during mouse development and integrated these data with published microarray and next-generation sequencing datasets as well as with newly produced PCR validation experiments. We show that a large fraction of non-exonic UCEs is transcribed across all developmental stages examined from only one DNA strand. Although the nature of these transcripts remains a mistery, our meta-analysis of RNA-Seq datasets indicates that they are unlikely to be short RNAs and that some of them might encode nuclear transcripts", "Our data shows that the concurrent presence of enhancer and transcript function in non-exonic UCE elements is more widespread than previously shown. Moreover through our own experiments as well as the use of next-generation sequencing datasets, we were able to show that the RNAs encoded by non-exonic UCEs are likely to be long RNAs transcribed from only one DNA strand", "Short ultraconserved promoter regions delineate a class of preferentially expressed alternatively spliced transcripts", "The importance of other classes of non-coding RNAs, such as long intergenic ncRNAs (lincRNAs) and transcribed ultraconserved regions (T-UCRs) as altered elements in neoplasia, is also gaining recognition.", "Other ncRNAs, such as PIWI-interacting RNAs (piRNAs), small nucleolar RNAs (snoRNAs), transcribed ultraconserved regions (T-UCRs) and large intergenic non-coding RNAs (lincRNAs) are emerging as key elements of cellular homeostasis.", "The majority of these regions map onto ultraconserved elements and we demonstrate that they can act as functional enhancers within the organism of origin, as well as in cross-transgenesis experiments, and that they are transcribed in extant species of Olfactores.", "Transcribed ultraconserved regions (T-UCRs) are a subset of 481 sequences longer than 200 bp, which are absolutely conserved between orthologous regions of human, rat and mouse genomes, and are actively transcribed.", "Highly conserved elements discovered in vertebrates are present in non-syntenic loci of tunicates, act as enhancers and can be transcribed during development.", "The Evf-2 noncoding RNA is transcribed from the Dlx-5/6 ultraconserved region and functions as a Dlx-2 transcriptional coactivator.", "In this report, we show that the Dlx-5/6 ultraconserved region is transcribed to generate an alternatively spliced form of Evf-1, the ncRNA Evf-2.", "These studies identify a critical role for TUC338 in regulation of transformed cell growth and of transcribed ultraconserved ncRNA as a unique class of genes involved in the pathobiology of HCC.", "Transcribed ultraconserved region (T-UCR) transcripts are a novel class of lncRNAs transcribed from ultraconserved regions (UCRs)", "The majority of these regions map onto ultraconserved elements and we demonstrate that they can act as functional enhancers within the organism of origin, as well as in cross-transgenesis experiments, and that they are transcribed in extant species of Olfactores", "Transcribed ultraconserved regions (T-UCRs) are a subset of 481 sequences longer than 200 bp, which are absolutely conserved between orthologous regions of human, rat and mouse genomes, and are actively transcribed", "Other ncRNAs, such as PIWI-interacting RNAs (piRNAs), small nucleolar RNAs (snoRNAs), transcribed ultraconserved regions (T-UCRs) and large intergenic non-coding RNAs (lincRNAs) are emerging as key elements of cellular homeostasis", "Transcribed ultraconserved region in human cancers.", "We show that a large fraction of non-exonic UCEs is transcribed across all developmental stages examined from only one DNA strand", "Although uc.338 is partially located within the poly(rC) binding protein 2 (PCBP2) gene, the transcribed ncRNA encoding uc.338 is expressed independently of PCBP2 and was cloned as a 590-bp RNA gene, termed TUC338", "Moreover through our own experiments as well as the use of next-generation sequencing datasets, we were able to show that the RNAs encoded by non-exonic UCEs are likely to be long RNAs transcribed from only one DNA strand." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/24037088", "http://www.ncbi.nlm.nih.gov/pubmed/20202189", "http://www.ncbi.nlm.nih.gov/pubmed/24384562", "http://www.ncbi.nlm.nih.gov/pubmed/22328099", "http://www.ncbi.nlm.nih.gov/pubmed/19660540", "http://www.ncbi.nlm.nih.gov/pubmed/21187392", "http://www.ncbi.nlm.nih.gov/pubmed/16705037", "http://www.ncbi.nlm.nih.gov/pubmed/23393190" ]

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[]

[ "S-adenosyl-L-methionine (AdoMet, SAM) is the methyl donor of DNA (cytosine-5)-methyltransferases. DNA (cytosine-5)-methyltransferases catalyze the transfer of a methyl group from S-adenosyl-L-methionine to the C-5 position of cytosine residues in DNA." ]

[ "S-adenosyl-L-methionine" ]

[ "The product of the dcm gene is the only DNA cytosine-C5 methyltransferase of Escherichia coli K-12; it catalyses transfer of a methyl group from S-adenosyl methionine (SAM) to the C-5 position of the inner cytosine residue of the cognate sequence CCA/TGG. ", "Deoxycytosine methylase (Dcm) enzyme activity causes mutagenesis in vitro either directly by enzyme-induced deamination of cytosine to uracil in the absence of the methyl donor, S-adenosylmethionine (SAM), or indirectly through spontaneous deamination of [5-methyl]cytosine to thymine", "In the absence of DNA substrate, the DNA methyltransferase (MTase) M.BspRI can methylate itself using the methyl donor S-adenosyl-L-methionine (AdoMet). The methyl group is transferred to two Cys residues of the MTase.", "The reaction is fairly insensitive to the methyl donor in the reaction, S-adenosylmethionine.", "Formation of the complex was dependent upon the presence of the methyl donor S-adenosylmethionine, suggesting that it comprises an enzyme-linked 5-substituted dihydrocytosine moiety in DNA. ", "The DNA (cytosine-5)-methyltransferase (m5C-MTase) M.BspRI is able to accept the methyl group from the methyl donor S-adenosyl-L-methionine (AdoMet) in the absence of DNA. Transfer of the methyl group to the enzyme is a slow reaction relative to DNA methylation. S", "Here, we report the structure of HhaI methyltransferase in complex with DNA containing a south-constrained abasic carbocyclic sugar at the target site in the presence of the methyl donor byproduct AdoHcy." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/7578083", "http://www.ncbi.nlm.nih.gov/pubmed/8441638", "http://www.ncbi.nlm.nih.gov/pubmed/1584813", "http://www.ncbi.nlm.nih.gov/pubmed/11208790", "http://www.ncbi.nlm.nih.gov/pubmed/8065896", "http://www.ncbi.nlm.nih.gov/pubmed/15273274", "http://www.ncbi.nlm.nih.gov/pubmed/7607467" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004248", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D019175", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0003886" ]

[ "Experimental data support the concept that Ewing sarcoma and peripheral neuroepithelioma are both peripheral primitive neuroectodermal neoplasms, differing only in the extent of neuroectodermal phenotype and morphological differentiation." ]

[ "yes" ]

[ "The term \"small round-cell tumor\" describes a group of highly aggressive malignant tumors composed of relatively small and monotonous undifferentiated cells with high nuclear to cytoplasmic ratios. This group includes Ewing's sarcoma (ES), peripheral neuroepithelioma (aka, primitive neuroectodermal tumor or extraskeletal ES), peripheral neuroblastoma (\"classic-type\"), rhabdomyosarcoma, desmoplastic small round-cell tumor, lymphoma, leukemia, small-cell osteosarcoma, small-cell carcinoma (either undifferentiated or neuroendocrine), olfactory neuroblastoma, cutaneous neuroendocrine carcinoma (aka, Merkel-cell carcinoma), small-cell melanoma, and mesenchymal chondrosarcoma. Their clinical presentations often overlap, thus making a definitive diagnosis problematic in some cases", "AIMS: To retrospectively study the DNA content in a series of childhood Ewing Family Tumors (EFT), and to investigate its prognostic value. METHODS: The study was performed on a series of 27 EFTs (osseous Ewing's sarcoma, 18 cases; extraosseous Ewing's sarcoma, 2; peripheral neuroepithelioma, 4; Askin Rosai tumors, 3", "To improve the prognosis of patients with poor-risk peripheral primitive neuroectodermal tumors (pPNETs; including peripheral neuroepithelioma and Ewing's sarcoma)", "Large group of small-round-cell tumours of soft tissues and bone represents a complex diagnostic problem for the pathologists. Neuronal nature of many tumours from this group is proven by means of new methods--immunophenotypic analysis, tissue culture, cytogenetics. Peripheral neuroepithelioma, Ewing tumour, primitive neuroectodermal tumour (PNET), Askin tumour belong to these neoplasms", "Comparison of Ewing's sarcoma of bone and peripheral neuroepithelioma. An immunocytochemical and ultrastructural analysis of two primitive neuroectodermal neoplasms", "Ewing's sarcoma of bone (ESB) and peripheral neuroepithelioma (PN) are frequently considered to be different tumors. Some researchers have suggested that PN is morphologically a neuroectodermal Ewing's sarcoma. We sought to determine the extent of neuroectodermal features in conventional ESB on direct patient material (25 cases) and to compare these tumors with a similar group of readily diagnosed PNs (10 cases)", "Neuroectodermal antigens (neuron-specific enolase, Leu-7 [HNK-1], neurofilament 200 kd, and S100) were found in nine of 10 cases of PN and in 17 of 25 cases of ESB", "These data support the concept that ESB and PN are both peripheral primitive neuroectodermal neoplasms, differing only in extent of neuroectodermal phenotype and morphological differentiation", "Besides these antigenic features, Ewing sarcoma cells are characterized by a specific t(11;22)(q24;q12) translocation also observed in neuroepithelioma, a neuroectodermal tumor, suggesting a possible evolutionary related origin.", "Ewings sarcoma (ES) and peripheral neuroepithelioma (PN) are closely related tumors, and it can be difficult to distinguish them from other small-round-cell tumors (SRCTs).", "The presence of this translocation in Ewing sarcoma and peripheral primitive neuroectodermal tumor has been taken as evidence that these two tumors are related.", "Besides these antigenic features, Ewing sarcoma cells are characterized by a specific t(11;22)(q24;q12) translocation also observed in neuroepithelioma, a neuroectodermal tumor, suggesting a possible evolutionary related origin.", "Indistinguishable patterns of protooncogene expression in two distinct but closely related tumors: Ewing's sarcoma and neuroepithelioma.", "Ewing's sarcoma (ES) and peripheral neuroepithelioma (PN) are related tumors, possibly of neural crest origin, which are cytogenetically characterized by the specific translocation t(11;22)(q24;q12).", "Ewing's sarcoma/peripheral primitive neuroectodermal tumors (ES/pPNET) are a group of small round cell sarcomas that show varying degrees of neuroectodermal differentiation characterized by translocation involving the EWS gene", "Ewing's sarcoma (ES) and peripheral neuroepithelioma (PN) are closely related tumors, and it can be difficult to distinguish them from other small-round-cell tumors (SRCTs)", "Ewing's sarcoma (ES) and peripheral neuroepithelioma (PN) are related tumors, possibly of neural crest origin, which are cytogenetically characterized by the specific translocation t(11;22)(q24;q12)", "This genetical similarity further supports a nosological concept according to which Askin's tumour, Ewing's sarcoma and peripheral neuroepithelioma represent phenotypic variations of the same tumour, namely the peripheral primitive neuroectodermal tumour.", "Besides these antigenic features, Ewing sarcoma cells are characterized by a specific t(11;22)(q24;q12) translocation also observed in neuroepithelioma, a neuroectodermal tumor, suggesting a possible evolutionary related origin" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/8204006", "http://www.ncbi.nlm.nih.gov/pubmed/25303625", "http://www.ncbi.nlm.nih.gov/pubmed/3390826", "http://www.ncbi.nlm.nih.gov/pubmed/9825003", "http://www.ncbi.nlm.nih.gov/pubmed/7595741", "http://www.ncbi.nlm.nih.gov/pubmed/7513503", "http://www.ncbi.nlm.nih.gov/pubmed/1283315", "http://www.ncbi.nlm.nih.gov/pubmed/10968707", "http://www.ncbi.nlm.nih.gov/pubmed/8321753", "http://www.ncbi.nlm.nih.gov/pubmed/8644855", "http://www.ncbi.nlm.nih.gov/pubmed/7771924", "http://www.ncbi.nlm.nih.gov/pubmed/3760036" ]

[]

[ "http://www.disease-ontology.org/api/metadata/DOID:3369", "http://www.disease-ontology.org/api/metadata/DOID:3368", "http://www.disease-ontology.org/api/metadata/DOID:4388", "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=D018241", "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" ]

[ "Sonidegib is a Hedghog signalling pathway inhibitor." ]

[ "Hedghog signalling pathway" ]

[ "The association between Hh activation status and tumor response to the Hh pathway inhibitor sonidegib (LDE225) was analyzed.", "Distinct molecular subgroups of medulloblastoma, including hedgehog (Hh) pathway-activated disease, have been reported. ", "We assessed the antitumour activity of sonidegib, a Hedgehog signalling inhibitor, in patients with advanced basal cell carcinoma.", "Among such pathways, RAS/RAF/MEK/ERK, PI3K/AKT/mTOR, EGFR, and Notch are of particular interest because agents that selectively inhibit these pathways are available and can be readily combined with agents such as vismodegib, sonidegib (LDE225), and BMS-833923, which target smoothened-a key Hh pathway regulator.", "This phase I trial was undertaken to determine the maximum tolerated dose (MTD), dose-limiting toxicities (DLT), safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary antitumor activity of the novel smoothened inhibitor sonidegib (LDE225), a potent inhibitor of hedgehog signaling, in patients with advanced solid tumors.", "The absorption, distribution, metabolism, and excretion of the hedgehog pathway inhibitor sonidegib (LDE225) were determined in healthy male subjects.", "Future studies, including one combining the Hh pathway inhibitor sonidegib and the JAK2 inhibitor ruxolitinib, are underway in patients with MF and will inform whether this combination approach can lead to true disease modification.", "We assessed the antitumour activity of sonidegib, a Hedgehog signalling inhibitor, in patients with advanced basal cell carcinoma.", "We assessed the antitumour activity of sonidegib, a Hedgehog signalling inhibitor, in patients with advanced basal cell carcinoma.METHODS: BOLT is an ongoing multicentre, randomised, double-blind, phase 2 trial. ", "PURPOSE: This phase I trial was undertaken to determine the maximum tolerated dose (MTD), dose-limiting toxicities (DLT), safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary antitumor activity of the novel smoothened inhibitor sonidegib (LDE225), a potent inhibitor of hedgehog signaling, in patients with advanced solid tumors. EXPERIMENTAL DESIGN: Oral sonidegib was administered to 103 patients with advanced solid tumors, including medulloblastoma and basal cell carcinoma (BCC), at doses ranging from 100 to 3,000 mg daily and 250 to 750 mg twice daily, continuously, with a single-dose pharmacokinetics run-in period. ", "PURPOSE: The absorption, distribution, metabolism, and excretion of the hedgehog pathway inhibitor sonidegib (LDE225) were determined in healthy male subjects. ", "Hedgehog pathway signalling is aberrantly activated in around 95% of tumours. We assessed the antitumour activity of sonidegib, a Hedgehog signalling inhibitor, in patients with advanced basal cell carcinoma.METHODS: BOLT is an ongoing multicentre, randomised, double-blind, phase 2 trial. Eligible patients had locally advanced basal cell carcinoma not amenable to curative surgery or radiation or metastatic basal cell carcinoma. ", "PURPOSE: The absorption, distribution, metabolism, and excretion of the hedgehog pathway inhibitor sonidegib (LDE225) were determined in healthy male subjects. METHODS: Six subjects received a single oral dose of 800 mg ¹⁴C-sonidegib (74 kBq, 2.0 µCi) under fasting conditions. ", " The absorption, distribution, metabolism, and excretion of the hedgehog pathway inhibitor sonidegib (LDE225) were determined in healthy male subjects. Six subjects received a single oral dose of 800 mg ¹⁴C-sonidegib (74 kBq, 2.0 µCi) under fasting conditions.", "Future studies, including one combining the Hh pathway inhibitor sonidegib and the JAK2 inhibitor ruxolitinib, are underway in patients with MF and will inform whether this combination approach can lead to true disease modification. .", "The association between Hh activation status and tumor response to the Hh pathway inhibitor sonidegib (LDE225) was analyzed.", " This phase I trial was undertaken to determine the maximum tolerated dose (MTD), dose-limiting toxicities (DLT), safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary antitumor activity of the novel smoothened inhibitor sonidegib (LDE225), a potent inhibitor of hedgehog signaling, in patients with advanced solid tumors. Oral sonidegib was administered to 103 patients with advanced solid tumors, including medulloblastoma and basal cell carcinoma (BCC), at doses ranging from 100 to 3,000 mg daily and 250 to 750 mg twice daily, continuously, with a single-dose pharmacokinetics run-in period.", "Preliminary clinical data also suggest that inhibition of the Hh pathway, alone or in combination with JAK2 inhibition, may enable disease modification in patients with MF. Future studies, including one combining the Hh pathway inhibitor sonidegib and the JAK2 inhibitor ruxolitinib, are underway in patients with MF and will inform whether this combination approach can lead to true disease modification.", "The absorption, distribution, metabolism, and excretion of the hedgehog pathway inhibitor sonidegib (LDE225) were determined in healthy male subjects. Six subjects received a single oral dose of 800 mg ¹⁴C-sonidegib (74 kBq, 2.", "including one combining the Hh pathway inhibitor sonidegib and the JAK2 inhibitor ruxolitinib,", "This phase I trial was undertaken to determine the maximum tolerated dose (MTD), dose-limiting toxicities (DLT), safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary antitumor activity of the novel smoothened inhibitor sonidegib (LDE225), a potent inhibitor of hedgehog signaling, in patients with advanced solid tumors. Oral sonidegib was administered to 103 patients with advanced solid tumors, including medulloblastoma and basal cell carcinoma (BCC), at doses ranging from 100 to 3,000 mg daily and 250 to 750 mg twice daily, continuously, with a single-dose pharmacokinetics run-in period.", "Hedgehog pathway signalling is aberrantly activated in around 95% of tumours. We assessed the antitumour activity of sonidegib, a Hedgehog signalling inhibitor, in patients with advanced basal cell carcinoma." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/24598114", "http://www.ncbi.nlm.nih.gov/pubmed/25981810", "http://www.ncbi.nlm.nih.gov/pubmed/24523439", "http://www.ncbi.nlm.nih.gov/pubmed/24613036", "http://www.ncbi.nlm.nih.gov/pubmed/25646180", "http://www.ncbi.nlm.nih.gov/pubmed/24817600", "http://www.ncbi.nlm.nih.gov/pubmed/24928708", "http://www.ncbi.nlm.nih.gov/pubmed/25473003" ]

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[ "In response to damage induced by DNA cross-linking agents, the S-phase checkpoint is inefficient in Fanconi anemia (FA) cells, leading to accumulation of secondary lesions, such as single- and double-strand breaks and gaps. The prolonged time in G2 phase seen in FA cells therefore exists in order to allow the cells to remove lesions which accumulated during the preceding abnormal S phase." ]

[ "In Fanconi anemia cells, the S-phase checkpoint is inefficient." ]

[ "We found that ICLs activate a branched pathway downstream of the ATR kinase: one branch depending on CHK1 activity and the other on the FANCs-RMN complex. The transient slow-down of DNA synthesis was abolished in cells lacking ATR, whereas CHK1-siRNA-treated cells, NBS1 or FA cells showed partial S-phase arrest", "Arrest of S-phase progression is impaired in Fanconi anemia cells", "Fanconi anemia (FA) is an inherited cancer-susceptibility disorder, characterized by genomic instability, hypersensitivity to DNA cross-linking agents, and a prolonged G2 phase of the cell cycle", "We observed a marked dose-dependent accumulation of FA cells in the G2 compartment after treatment with 4,5',8-trimethylpsoralen (Me(3)Pso) in combination with 365 nm irradiation", "Taken together, the above data suggest that, in response to damage induced by DNA cross-linking agents, the S-phase checkpoint is inefficient in FA cells. This would lead to accumulation of secondary lesions, such as single- and double-strand breaks and gaps. The prolonged time in G2 phase seen in FA cells therefore exists in order to allow the cells to remove lesions which accumulated during the preceding abnormal S phase", "Fanconi anemia (FA) is a genetic disorder defined by cellular hypersensitivity to DNA cross-linking agents, such as mitomycin C (MMC). MMC causes increased FA cell death, chromosome breakage, and accumulation in the G2 phase of the cell cycle", "DNA cross-linker-induced G2/M arrest in group C Fanconi anemia lymphoblasts reflects normal checkpoint function", "Cells from individuals with Fanconi anemia (FA) arrest excessively in the G2/M cell cycle compartment after exposure to low doses of DNA cross-linking agents", "Based on these studies we conclude that the aberrant G2/M arrest that typifies the response of FA(C) cells to low doses of cross-linking agents does not represent an abnormal cell cycle response but instead represents a normal cellular response to the excessive DNA damage that results in FA(C) cells following exposure to low doses of cross-linking agents", "Arrest of S-phase progression is impaired in Fanconi anemia cells.", "The 4N cell cycle delay in Fanconi anemia reflects growth arrest in late S phase." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/11035915", "http://www.ncbi.nlm.nih.gov/pubmed/9414295", "http://www.ncbi.nlm.nih.gov/pubmed/14988723", "http://www.ncbi.nlm.nih.gov/pubmed/9650445", "http://www.ncbi.nlm.nih.gov/pubmed/11749045" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D051856", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0007050", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D059447", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005199", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0022403" ]

[ "R-loops, transcriptionally-induced RNA:DNA hybrids, occurring at repeat tracts (CTG)n, (CAG)n, (CGG)n, (CCG)n and (GAA)n, are associated with diseases including myotonic dystrophy, Huntington's disease, fragile X and Friedreich's ataxia. Physiological R-loop formation at CpG island promoters can contribute to DNA replication origin specification at these regions, the most efficient replication initiation sites in mammalian cells. R-loops may also possess beneficial effects, as their widespread formation has been detected over CpG island promoters in human genes. R-loops are particularly enriched over G-rich terminator elements." ]

[ "G-rich elements", "CpG islands", "(CTG)n, (CAG)n, (CGG)n, (CCG)n and (GAA)n" ]

[ "R-loops, transcriptionally-induced RNA:DNA hybrids, occurring at repeat tracts (CTG)n, (CAG)n, (CGG)n, (CCG)n and (GAA)n, are associated with diseases including myotonic dystrophy, Huntington's disease, fragile X and Friedreich's ataxia", "Double-R-loop formation and processing to instability was extended to the expanded C9orf72 (GGGGCC)·(GGCCCC) repeats, known to cause amyotrophic lateral sclerosis and frontotemporal dementia, providing the first suggestion through which these repeats may become unstable. ", "Here we propose that physiological R-loop formation at CpG island promoters can contribute to DNA replication origin specification at these regions, the most efficient replication initiation sites in mammalian cells.", "R-loops may also possess beneficial effects, as their widespread formation has been detected over CpG island promoters in human genes", "Furthermore, we have previously shown that R-loops are particularly enriched over G-rich terminator elements", "R-loops associated with triplet repeat expansions", "Periodic DNA patrolling underlies diverse functions of Pif1 on R-loops and G-rich DNA", "Ginno et al. (2012) describe unusual sequence features at promoter CpG islands that can lead to formation of persistent RNA-DNA hybrids (R loops), which are proposed to prevent genomic DNA methylation", "R loops stimulate genetic instability of CTG.CAG repeats", " We demonstrate, using biochemical and genetic approaches, that the formation of stable RNA.DNA hybrids enhances the instability of CTG.CAG repeat tracts.", " The R-loop, previously characterized in vitro at the leading strand replication origin (OH), is isolated as a native RNA-DNA hybrid copurifying with mtDNA", "All of these R-loops arise upon generation of a G-rich RNA strand by an RNA polymerase upon transcription of a C-rich DNA template strand.", "Finally, non-denaturing bisulfite mapping of the displaced single-stranded DNA confirmed R-loop formation at the endogenous FMR1 locus and further indicated that R-loops formed over CGG repeats may be prone to structural complexities, including hairpin formation, not commonly associated with other R-loops", "We have observed that transcription through the GC-rich FMR1 5&apos;UTR region favors R-loop formation, with the nascent (G-rich) RNA forming a stable RNA:DNA hybrid with the template DNA strand, thereby displacing the non-template DNA strand", "which is rich in AT and not prone to form R-loops,", "Finally, non-denaturing bisulfite mapping of the displaced single-stranded DNA confirmed R-loop formation at the endogenous FMR1 locus and further indicated that R-loops formed over CGG repeats may be prone to structural complexities, including hairpin formation, not commonly associated with other R-loops." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/16793409", "http://www.ncbi.nlm.nih.gov/pubmed/25147206", "http://www.ncbi.nlm.nih.gov/pubmed/24843019", "http://www.ncbi.nlm.nih.gov/pubmed/20080737", "http://www.ncbi.nlm.nih.gov/pubmed/15531884", "http://www.ncbi.nlm.nih.gov/pubmed/18986989", "http://www.ncbi.nlm.nih.gov/pubmed/25296254", "http://www.ncbi.nlm.nih.gov/pubmed/25972891", "http://www.ncbi.nlm.nih.gov/pubmed/22464440", "http://www.ncbi.nlm.nih.gov/pubmed/24787137", "http://www.ncbi.nlm.nih.gov/pubmed/24743386" ]

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[ "Mutation of aryl hydrocarbon receptor interacting protein (AIP) gene was implicated in the familial isolated pituitary adenoma (FIPA) syndrome. About 20% of the families with FIPA harbor inactivating mutation in AIP gene." ]

[ "aryl hydrocarbon receptor interacting protein" ]

[ "The cause of familial isolated pituitary adenomas (FIPA) remains unknown in a high percentage of cases, but the AIP gene plays an important role in the etiology. ", "Familial isolated pituitary adenoma caused by a Aip gene mutation not described before in a family context.", "We report a Spanish family with FIPA in whom a mutation in the AIP gene previously unreported in a familiar context was identified.", "FIPA, an autosomal-dominant disease with variable penetrance, is explained in 20% of patients by germline mutations in the tumor suppressor aryl hydrocarbon receptor interacting protein(AIP), while no gene abnormality has been identified to date in the majority of the FIPA families.", "Understanding the tumorigenic process in AIP-positive and AIP-negative FIPA patients could result in better diagnostic and treatment options for both familial and sporadic cases.", "The aryl hydrocarbon receptor interacting protein (AIP) gene has a major role in the pathogenesis of familial isolated pituitary adenoma.", " The discovery of heterozygous, loss-of-function germline mutations in the gene encoding the aryl hydrocarbon receptor interacting protein (AIP) in 2006 has subsequently enabled the identification of a mutation in this gene in 20% of FIPA families and 20% of childhood-onset simplex soma- totroph adenomas.", " This review aims to summarize currently available clinical data on AIP mutation-positive and negative FIPA patients.", "[Aryl hydrocarbon receptor interacting protein gene and familial isolated pituitary adenomas].", "Many heterozygous mutations have been discovered in AIP in about 20% of FIPA families. ", "Germline mutations of aryl-hydrocarbon-receptor interacting protein (AIP) are associated with pituitary adenoma predisposition. They occur in 20 % of familial isolated pituitary adenoma (FIPA) and in about 3-5 % of sporadic pituitary adenomas, especially in early onset somatotropinomas and prolactinomas. ", "We report a FIPA family harbouring an AIP R16H change, supporting the hypothesis that the latter represents a variant of unknown significance.", "Germline mutations in the aryl-hydrocarbon interacting protein gene are identified in around 25% of familial isolated pituitary adenoma kindreds. ", "Genetic analysis in a patient presenting with meningioma and familial isolated pituitary adenoma (FIPA) reveals selective involvement of the R81X mutation of the AIP gene in the pathogenesis of the pituitary tumor.", "About 20 % of the families with FIPA harbor inactivating mutation in aryl hydrocarbon receptor-interacting protein gene (AIP) associated with loss of heterozygosity of the same genetic locus (11q13) in the tumor. Rarely different types of extra-pituitary tumors have been described in the setting of AIP mutation-positive FIPA. ", "Mutations in AIP account only for 15-25% of FIPA families. ", "In 20-40% of families with this syndrome, mutations have been identified in the aryl hydrocarbon receptor interacting protein gene while in the rest of the families the causative gene or genes have not been identified. ", "Germline mutations in the aryl hydrocarbon receptor-interacting protein gene (AIP) predispose to young-onset pituitary tumours, most often to GH- or prolactin-secreting adenomas, and most of these patients belong to familial isolated pituitary adenoma families.", "We also briefly describe the genetic basis of three other inherited states predisposing individuals to endocrine tumors, namely Carney's syndrome, hyperparathyroidism type 2 (HRPT2) and familial isolated pituitary adenoma (FIPA), which are related to inactivating mutations in the PRKAR1-alpha, HRPT2 and AIP genes, respectively.", "The identification of mutations in the Aryl hydrocarbon receptor interacting protein (AIP) gene in a subset of familial isolated pituitary adenoma (FIPA) cases has recently expanded our understanding of the pathophysiology of inherited pituitary adenoma disorders.", "Several studies and reviews have assessed the genetic and clinical features of AIP-mutated FIPA patients, which range from a complete lack of symptoms in adult/elderly individuals to large, aggressive early-onset pituitary tumors.", "In 20% of FIPA families, heterozygous mutations have been described in the aryl hydrocarbon receptor interacting (AIP) gene, whereas in other families the causative gene(s) are unknown.", "A novel C-terminal nonsense mutation, Q315X, of the aryl hydrocarbon receptor-interacting protein gene in a Japanese familial isolated pituitary adenoma family.", "Familial isolated pituitary adenomas (FIPA) and the pituitary adenoma predisposition due to mutations in the aryl hydrocarbon receptor interacting protein (AIP) gene.", "Germline mutations in the aryl-hydrocarbon interacting protein gene are identified in around 25% of familial isolated pituitary adenoma kindreds.", "Mutations of the aryl hydrocarbon receptor interacting protein (AIP) gene are associated with pituitary adenomas that usually occur as familial isolated pituitary adenomas (FIPA).", "Clinical experience in the screening and management of a large kindred with familial isolated pituitary adenoma due to an aryl hydrocarbon receptor interacting protein (AIP) mutation.", "Cyclin-dependent kinase inhibitor 1B (CDKN1B) gene variants in AIP mutation-negative familial isolated pituitary adenoma kindreds.", "Although the cause of familial isolated pituitary adenoma (FIPA) remains unknown in many cases, germline mutations in the aryl hydrocarbon receptor-interacting protein (AIP) gene were identified in approximately 20 % of families with FIPA", "The cause of familial isolated pituitary adenomas (FIPA) remains unknown in a high percentage of cases, but the AIP gene plays an important role in the etiology", "FIPA, an autosomal-dominant disease with variable penetrance, is explained in 20% of patients by germline mutations in the tumor suppressor aryl hydrocarbon receptor interacting protein(AIP), while no gene abnormality has been identified to date in the majority of the FIPA families", "Germline mutations in the aryl-hydrocarbon interacting protein gene are identified in around 25% of familial isolated pituitary adenoma kindreds", "The identification of mutations in the Aryl hydrocarbon receptor interacting protein (AIP) gene in a subset of familial isolated pituitary adenoma (FIPA) cases has recently expanded our understanding of the pathophysiology of inherited pituitary adenoma disorders", "To date, the number of molecular genetic factors unequivocally linked to pituitary tumours can be counted on the fingers of one hand: (1) GNAS1 activation in acromegaly; (2) the MENIN and p27Kip1 (CDKN1B) mutations associated with multiple endocrine neoplasia type 1; (3) mutations of PRKA1RA with loss of 17q22-24 in Carney complex, and (4) aryl hydrocarbon receptor interacting protein gene mutations in 15% of familial isolated pituitary adenomas and 50% of familial isolated acromegaly" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/23743763", "http://www.ncbi.nlm.nih.gov/pubmed/24078436", "http://www.ncbi.nlm.nih.gov/pubmed/24050928", "http://www.ncbi.nlm.nih.gov/pubmed/20457215", "http://www.ncbi.nlm.nih.gov/pubmed/22915287", "http://www.ncbi.nlm.nih.gov/pubmed/17961654", "http://www.ncbi.nlm.nih.gov/pubmed/23633209", "http://www.ncbi.nlm.nih.gov/pubmed/17244780", "http://www.ncbi.nlm.nih.gov/pubmed/21450940", "http://www.ncbi.nlm.nih.gov/pubmed/23286415", "http://www.ncbi.nlm.nih.gov/pubmed/23652674", "http://www.ncbi.nlm.nih.gov/pubmed/21778740", "http://www.ncbi.nlm.nih.gov/pubmed/17893250", "http://www.ncbi.nlm.nih.gov/pubmed/22527616", "http://www.ncbi.nlm.nih.gov/pubmed/21454441", "http://www.ncbi.nlm.nih.gov/pubmed/20570174", "http://www.ncbi.nlm.nih.gov/pubmed/24423289", "http://www.ncbi.nlm.nih.gov/pubmed/20616498", "http://www.ncbi.nlm.nih.gov/pubmed/22584704", "http://www.ncbi.nlm.nih.gov/pubmed/24996936", "http://www.ncbi.nlm.nih.gov/pubmed/20669561", "http://www.ncbi.nlm.nih.gov/pubmed/20616502", "http://www.ncbi.nlm.nih.gov/pubmed/19883897", "http://www.ncbi.nlm.nih.gov/pubmed/24366639", "http://www.ncbi.nlm.nih.gov/pubmed/23371967", "http://www.ncbi.nlm.nih.gov/pubmed/20506337", "http://www.ncbi.nlm.nih.gov/pubmed/20833337", "http://www.ncbi.nlm.nih.gov/pubmed/23310926", "http://www.ncbi.nlm.nih.gov/pubmed/24789813", "http://www.ncbi.nlm.nih.gov/pubmed/22291433", "http://www.ncbi.nlm.nih.gov/pubmed/23038625", "http://www.ncbi.nlm.nih.gov/pubmed/17993773", "http://www.ncbi.nlm.nih.gov/pubmed/21498161" ]

[]

[]

[ "The following mutations of troponin C gene have been found to cause hypertrophic cardiomyopathy: L29Q; A8V; A31S; E134D; c.363dupG; A23Q; D145E and C84Y" ]

[ "L29Q", "A8V", "A31S", "E134D", "c.363dupG", "A23Q", "D145E", "C84Y" ]

[ "The Ca(2+) binding properties of the FHC-associated cardiac troponin C (cTnC) mutation L29Q were examined in isolated cTnC, troponin complexes, reconstituted thin filament preparations, and skinned cardiomyocytes. ", "Effects of calcium binding and the hypertrophic cardiomyopathy A8V mutation on the dynamic equilibrium between closed and open conformations of the regulatory N-domain of isolated cardiac troponin C", "We also used PRE data to assess the structural effects of a familial hypertrophic cardiomyopathy point mutation located within the N-domain of cTnC (A8V). ", "A mutation in TNNC1-encoded cardiac troponin C, TNNC1-A31S, predisposes to hypertrophic cardiomyopathy and ventricular fibrillation.", "Here, we report clinical and functional characterization of a novel TNNC1 mutation, A31S, identified in a pediatric HCM proband with multiple episodes of ventricular fibrillation and aborted sudden cardiac death.", "In summary, we report a novel mutation in the TNNC1 gene that is associated with HCM pathogenesis and may predispose to the pathogenesis of a fatal arrhythmogenic subtype of HCM.", "The objective of this work was to investigate the effect of hypertrophic cardiomyopathy-linked A8V and E134D mutations in cardiac troponin C (cTnC) on the response of reconstituted thin filaments to calcium upon phosphorylation of cardiac troponin I (cTnI) by protein kinase A.", "We describe a novel type of mutation (c.363dupG) in Troponin C, a rare form of hypertrophic cardiomyopathy.", "We report the first frameshift mutation (c.363dupG or p.Gln122AlafsX30) in Troponin C causing hypertrophic cardiomyopathy (and sudden cardiac death) in a 19-year-old male, and have demonstrated that the mutation segregates with hypertrophic cardiomyopathy within the family.", "One mutant (A23Q) was found with HCM-like properties (increased Ca(2+) sensitivity of force and normal levels of ATPase inhibition).", "In this study, we investigated the effects of hypertrophic cardiomyopathy-linked mutations A8V, E134D, and D145E in cardiac troponin C on the properties of the C-domain sites.", "Recently four new hypertrophic cardiomyopathy mutations in cardiac troponin C (cTnC) (A8V, C84Y, E134D, and D145E) were reported, and their effects on the Ca(2+) sensitivity of force development were evaluated", "Comprehensive open reading frame/splice site mutation analysis of TNNC1 performed on 1025 unrelated HCM patients enrolled over the last 10 years revealed novel missense mutations in TNNC1: A8V, C84Y, E134D, and D145E.", "The cardiac troponin C (cTnC) mutation, L29Q, has been found in a patient with familial hypertrophic cardiomyopathy.", "These results demonstrate that the L29Q mutation enhances the Ca(2+)-binding characteristics of cTnC and that when incorporated into cardiac myocytes, this mutant alters myocyte contractility.", "Cardiac troponin C-L29Q, related to hypertrophic cardiomyopathy, hinders the transduction of the protein kinase A dependent phosphorylation signal from cardiac troponin I to C.", "This mutation leads to a leucine-glutamine exchange at position 29 in the nonfunctional calcium-binding site of cTnC. " ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/19439414", "http://www.ncbi.nlm.nih.gov/pubmed/20459070", "http://www.ncbi.nlm.nih.gov/pubmed/23425245", "http://www.ncbi.nlm.nih.gov/pubmed/21262074", "http://www.ncbi.nlm.nih.gov/pubmed/22489623", "http://www.ncbi.nlm.nih.gov/pubmed/16302972", "http://www.ncbi.nlm.nih.gov/pubmed/18572189", "http://www.ncbi.nlm.nih.gov/pubmed/18285522", "http://www.ncbi.nlm.nih.gov/pubmed/20566645", "http://www.ncbi.nlm.nih.gov/pubmed/19506933", "http://www.ncbi.nlm.nih.gov/pubmed/24260207", "http://www.ncbi.nlm.nih.gov/pubmed/22815480" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D002312", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D019209", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009154" ]

[ "Ear acupressure (EAP) and ear acupuncture have been used for smoking cessation, and some positive results have been reported.\nAuricular (ear) acupressure has been purported to be beneficial in achieving smoking cessation in some studies, while in others has been deemed insignificant.\nThe combined acupuncture-education group showing the greatest effect from treatment." ]

[]

[ "Ear acupressure (EAP) and ear acupuncture have been used for smoking cessation, and some positive results have been reported", "Auricular (ear) acupressure has been purported to be beneficial in achieving smoking cessation in some studies, while in others has been deemed insignificant", "Acupuncture combined with auricular point sticking and pressing has reliable therapeutic effect for smoking cessation", "Acupuncture has been promoted as a treatment modality for smoking cessation. However, its efficacy still remains controversial", "Our results showed that auricular acupuncture did not have a better efficacy in smoking cessation compared to sham acupuncture. Combined acupuncture with behavior counseling or with nicotine replacement therapy should be used in further smoking cessation trials to enhance the success rate of smoking cessation.", "Combining ten studies showed auricular acupuncture at 'correct' points to be more effective than control interventions, odds ratio 2.24 (95% CI 1.61, 3.10),", "Auricular acupuncture appears to be effective for smoking cessation, but the effect may not depend on point location.", "The combination of auricular acupressure and Internet-assisted smoking cessation program was more efficacious than auricular acupressure alone in terms of quit rate.", "auricular acupuncture in smoking cessation has some effect.", "With a one-year success rate of 41.1% ear acupuncture is a competitive alternative to orthodox medicine withdrawal methods. Acupuncture treatment can be applied and adapted individually, furthermore it is economical and without side effects.", "Auriculotherapy is an useful aid for giving up smoking. It is easy and painless, has no secondary effects and it is economic.", "the combined acupuncture-education group showing the greatest effect from treatment.", "Acupuncture and education, alone and in combination, significantly reduce smoking; however, combined they show a significantly greater effect, as seen in subjects with a greater pack-year history.", "A double blind, randomized, placebo-controlled clinical study was conducted to evaluate the efficacy of laser acupuncture treatment in adolescent smokers. ", "Thus, there was no significant difference in the rates of smoking cessation in the treatment and control groups.", "This simple ear electroacupuncture treatment was significantly more effective in helping volunteers to quit smoking than placebo treatment." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/24030452", "http://www.ncbi.nlm.nih.gov/pubmed/17264832", "http://www.ncbi.nlm.nih.gov/pubmed/15861492", "http://www.ncbi.nlm.nih.gov/pubmed/16566674", "http://www.ncbi.nlm.nih.gov/pubmed/22373002", "http://www.ncbi.nlm.nih.gov/pubmed/17698433", "http://www.ncbi.nlm.nih.gov/pubmed/11154059", "http://www.ncbi.nlm.nih.gov/pubmed/10024707", "http://www.ncbi.nlm.nih.gov/pubmed/12356614", "http://www.ncbi.nlm.nih.gov/pubmed/15004442", "http://www.ncbi.nlm.nih.gov/pubmed/18405159", "http://www.ncbi.nlm.nih.gov/pubmed/12416359" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D026881", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012907", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016540", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D020831", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D015669" ]

[ "H3K9me3 is the major marker of constitutive heterochromatin. Other histone methylation marks usually found in constitutive heterochromatin, are H4K20me3 and H3K79me3. Classical histone modifications associated with heterochromatin include H3K9me2, H3K27me1 and H3K27me2. Histone H3 trimethylation at lysine 36 is associated with constitutive and facultative heterochromatin. H3S10 phosphorylation marks constitutive heterochromatin during interphase in early mouse embryos until the 4-cell stage" ]

[ "H3S10p", "H3K36me3", "H4K20me3", "H3K9me3", "H3K79me3", "H3K9me2", "H3K27me1", "H3K27me2", "H3K27me3" ]

[ "H3S10 phosphorylation marks constitutive heterochromatin during interphase in early mouse embryos until the 4-cell stage", "We show here that the maternally inherited Snurf-Snrpn 3-Mb region, which is silenced by a potent transcription repressive mechanism, is uniformly enriched in histone methylation marks usually found in constitutive heterochromatin, such as H4K20me3, H3K9me3, and H3K79me3.", "This result indicates that H3K36me3 is associated with both facultative and constitutive heterochromatin.", "Classical histone modifications associated with heterochromatin, including H3K9me2, H3K27me1 and H3K27me2, were distributed throughout both A and B chromosomes.", "In this review, available data will be evaluated concerning (1) the phylogenetic distribution of H3K9me as heterochromatin-specific histone modification and its evolutionary stability in relation to other epigenetic marks, (2) known families of H3K9 methyltransferases, (3) their responsibility for the formation of constitutive heterochromatin and (4) the evolution of Su(var)3-9-like and SUVH-like H3K9 methyltransferases", " While these regions were furthermore largely devoid of the constitutive heterochromatin marker H3K9-me3, we observed rapid and widespread deposition of H3K27-me3 across latent KSHV genomes, a bivalent modification which is able to repress transcription in spite of the simultaneous presence of activating marks.", "Histone modifications in Arabidopsis- high methylation of H3 lysine 9 is dispensable for constitutive heterochromatin", "The recent discovery of the first histone Lys methyltransferase has allowed the identification of a molecular mechanism in which the specific methylation of histone H3 at Lys9 generates a binding site for heterochromatin-associated proteins.", "At the SUMO-1 labelled areas, the presence of HP1alpha protein, as well as of trimethylated H3-K9 and H4-K20 histone modifications, supports a role for SUMO-1 in constitutive heterochromatin organization.", "Surprisingly, the marsupial Xi was stably enriched for modifications associated with constitutive heterochromatin in all eukaryotes (H4K20me3, H3K9me3).", "Constitutive heterochromatin during mouse oogenesis: the pattern of histone H3 modifications and localization of HP1alpha and HP1beta proteins.", "In fission yeast, heterochromatin formation requires RNAi and the histone H3K9 methyltransferase complex CLRC, composed of Clr4, Raf1, Raf2, Cul4, and Rik1. ", "Methylation of histone H3 at lysine 9 (H3-Lys9) by site-specific histone methyltransferases (Suv39h HMTases) marks constitutive heterochromatin. ", "H3S10 phosphorylation marks constitutive heterochromatin during interphase in early mouse embryos until the 4-cell stage.", "In placental mammals non-coding XIST RNA triggers silencing of one X (Xi) and recruits a characteristic suite of epigenetic modifications, including the histone mark H3K27me3." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/11740497", "http://www.ncbi.nlm.nih.gov/pubmed/21541345", "http://www.ncbi.nlm.nih.gov/pubmed/17710556", "http://www.ncbi.nlm.nih.gov/pubmed/11356363", "http://www.ncbi.nlm.nih.gov/pubmed/22319459", "http://www.ncbi.nlm.nih.gov/pubmed/22572731", "http://www.ncbi.nlm.nih.gov/pubmed/18592385", "http://www.ncbi.nlm.nih.gov/pubmed/18987983", "http://www.ncbi.nlm.nih.gov/pubmed/12581305", "http://www.ncbi.nlm.nih.gov/pubmed/20532208", "http://www.ncbi.nlm.nih.gov/pubmed/17891782", "http://www.ncbi.nlm.nih.gov/pubmed/21803857" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D006570", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D002843" ]

[ "GV1001 is a 16-amino-acid vaccine peptide derived from the human telomerase reverse transcriptase sequence. It has been developed as a vaccine against various cancers." ]

[ "human telomerase reverse transcriptase" ]

[ "A reverse-transcriptase-subunit of telomerase (hTERT) derived peptide, GV1001, has been developed as a vaccine against various cancers. ", "Telomerase (GV1001) vaccination together with gemcitabine in advanced pancreatic cancer patients.", "A study was conducted to investigate safety and immunogenicity in non-resectable pancreatic carcinoma patients using a 16-amino acid telomerase peptide (GV1001) for vaccination in combination with GM-CSF and gemcitabine as first line treatment. ", "Telomerase vaccination (GV1001) in combination with chemotherapy appeared to be safe but the immune responses were weak and transient. ", "Gemcitabine and capecitabine with or without telomerase peptide vaccine GV1001 in patients with locally advanced or metastatic pancreatic cancer (TeloVac): an open-label, randomised, phase 3 trial.", "BACKGROUND: We aimed to assess the efficacy and safety of sequential or simultaneous telomerase vaccination (GV1001) in combination with chemotherapy in patients with locally advanced or metastatic pancreatic cancer.", "Novel vaccine peptide GV1001 effectively blocks β-amyloid toxicity by mimicking the extra-telomeric functions of human telomerase reverse transcriptase.", "GV1001 is a 16-amino-acid vaccine peptide derived from the human telomerase reverse transcriptase sequence.", "Together, these results suggest that GV1001 possesses neuroprotective effects against Aβ₂₅₋₃₅ oligomer in NSCs and that these effects are mediated through mimicking the extra-telomeric functions of human telomerase reverse transcriptase, including the induction of cellular proliferation, anti-apoptotic effects, mitochondrial stabilization, and anti-aging and anti-oxidant effects.", "Peptide GV1001 is a peptide vaccine representing a 16-amino acid human telomerase reverse transcriptase sequence, which has been reported to possess potential antineoplastic and anti-inflammatory activity. ", "Based on this review, the most promising current telomerase targeting therapeutics are the antisense oligonucleotide inhibitor GRN163L and immunotherapies that use dendritic cells (GRVAC1), hTERT peptide (GV1001) or cryptic peptides (Vx-001).", "A reverse-transcriptase-subunit of telomerase (hTERT) derived peptide, GV1001, has been developed as a vaccine against various cancers.", "Of the increasing number of immunological agents, the GV1001 antitelomerase vaccine holds some interest.", "A reverse-transcriptase-subunit of telomerase (hTERT) derived peptide, GV1001, has been developed as a vaccine against various cancers.", "Peptide GV1001 is a peptide vaccine representing a 16-amino acid human telomerase reverse transcriptase sequence, which has been reported to possess potential antineoplastic and anti-inflammatory activity.", "It places GV1001 in the context of other immunotherapeutic approaches targeting telomerase and assesses the chances of the vaccine becoming a future standard of care in the treatment of cancer.", "GV1001 is a telomerase-specific, promiscuous class II peptide vaccine which is currently in an advanced stage of clinical development.", "The study is a proof-of-principle trial evaluating toxicity, immune response, and clinical response in melanoma patients after combined therapy with temozolomide and the telomerase peptide vaccine GV1001.", "Telomerase-specific GV1001 peptide vaccination fails to induce objective tumor response in patients with cutaneous T cell lymphoma.", "This article reviews the biological rationale underpinning the design of ongoing studies with the vaccine as well as its immunogenicity and clinical activity. It places GV1001 in the context of other immunotherapeutic approaches targeting telomerase and assesses the chances of the vaccine becoming a future standard of care in the treatment of cancer.", "It places GV1001 in the context of other immunotherapeutic approaches targeting telomerase and assesses the chances of the vaccine becoming a future standard of care in the treatment of cancer. .", "Human telomerase reverse transcriptase (hTERT), the rate-limiting subunit of the telomerase complex, is therefore an attractive target for cancer vaccination. The present review provides an update on the development of GV1001, a peptide vaccine representing a 16-aa hTERT sequence.", "It places GV1001 in the context of other immunotherapeutic approaches targeting telomerase and assesses the chances of the vaccine becoming a future standard of care in the treatment of cancer.", "Of the increasing number of immunological agents, the GV1001 antitelomerase vaccine holds some interest.", "GV1001 is a 16-amino-acid vaccine peptide derived from the human telomerase reverse transcriptase sequence.", "Based on this review, the most promising current telomerase targeting therapeutics are the antisense oligonucleotide inhibitor GRN163L and immunotherapies that use dendritic cells (GRVAC1), hTERT peptide (GV1001) or cryptic peptides (Vx-001)." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/24815142", "http://www.ncbi.nlm.nih.gov/pubmed/19072345", "http://www.ncbi.nlm.nih.gov/pubmed/24954781", "http://www.ncbi.nlm.nih.gov/pubmed/21377838", "http://www.ncbi.nlm.nih.gov/pubmed/19388882", "http://www.ncbi.nlm.nih.gov/pubmed/23827187", "http://www.ncbi.nlm.nih.gov/pubmed/20822343", "http://www.ncbi.nlm.nih.gov/pubmed/22841437", "http://www.ncbi.nlm.nih.gov/pubmed/21586625", "http://www.ncbi.nlm.nih.gov/pubmed/24919654", "http://www.ncbi.nlm.nih.gov/pubmed/24439482", "http://www.ncbi.nlm.nih.gov/pubmed/24411674" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D014612", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004798" ]

[ "IκB degradation involves ubiquitination mediated by a specific E3 ubiquitin ligase SCF(β-TrCP). SCF(β-TrCP) -mediated IκB ubiquitination and degradation is a very efficient process, often resulting in complete degradation of the key inhibitor IκBα within a few minutes of cell stimulation.", "IkappaB degradation is dependent upon its phosphorylation by the IkappaB kinase (IKK) complex and subsequent ubiquitination facilitated by beta-Trcp E3 ubiquitin ligase.Sequence comparison analysis showed sequence motif identity between CLU and beta-transducin repeat-containing protein (beta-TrCP), a main E3 ubiquitin ligase involved in IkappaB-alpha degradation.", "IkappaB degradation is dependent upon its phosphorylation by the IkappaB kinase (IKK) complex and subsequent ubiquitination facilitated by beta-Trcp E3 ubiquitin ligase. SCF(β-TrCP) -mediated IκB ubiquitination and degradation is a very efficient process, often resulting in complete degradation of the key inhibitor IκBα within a few minutes of cell stimulation." ]

[ "SCF(β-TrCP)", "SCF beta-transducin repeat-containing protein (beta-TrCP)", "beta-Trcp" ]

[ "IKK activation and IκB degradation involve different ubiquitination modes; the latter is mediated by a specific E3 ubiquitin ligase SCF(β-TrCP) . The F-box component of this E3, β-TrCP, recognizes the IκB degron formed following phosphorylation by IKK and thus couples IκB phosphorylation to ubiquitination. SCF(β-TrCP) -mediated IκB ubiquitination and degradation is a very efficient process, often resulting in complete degradation of the key inhibitor IκBα within a few minutes of cell stimulation. In vivo ablation of β-TrCP results in accumulation of all the IκBs and complete NF-κB inhibition. ", "Sequence comparison analysis showed sequence motif identity between CLU and beta-transducin repeat-containing protein (beta-TrCP), a main E3 ubiquitin ligase involved in IkappaB-alpha degradation.", "IkappaB degradation is dependent upon its phosphorylation by the IkappaB kinase (IKK) complex and subsequent ubiquitination facilitated by beta-Trcp E3 ubiquitin ligase.", "Here we show that beta-catenin stabilizes the mRNA encoding the F-box protein betaTrCP1, and identify the RNA-binding protein CRD-BP (coding region determinant-binding protein) as a previously unknown target of beta-catenin/Tcf transcription factor. CRD-BP binds to the coding region of betaTrCP1 mRNA. Overexpression of CRD-BP stabilizes betaTrCP1 mRNA and elevates betaTrCP1 levels (both in cells and in vivo), resulting in the activation of the Skp1-Cullin1-F-box protein (SCF)(betaTrCP) E3 ubiquitin ligase and in accelerated turnover of its substrates including IkappaB and beta-catenin.", " The multisubunit IkappaB kinase (IKK) responsible for inducible IkappaB phosphorylation is the point of convergence for most NF-kappaB-activating stimuli. IKK contains two catalytic subunits, IKKalpha and IKKbeta, both of which are able to correctly phosphorylate IkappaB. Gene knockout studies have shed light on the very different physiological functions of IKKalpha and IKKbeta. After phosphorylation, the IKK phosphoacceptor sites on IkappaB serve as an essential part of a specific recognition site for E3RS(IkappaB/beta-TrCP), an SCF-type E3 ubiquitin ligase, thereby explaining how IKK controls IkappaB ubiquitination and degradation. " ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/22435548", "http://www.ncbi.nlm.nih.gov/pubmed/17001349", "http://www.ncbi.nlm.nih.gov/pubmed/16778892", "http://www.ncbi.nlm.nih.gov/pubmed/10837071", "http://www.ncbi.nlm.nih.gov/pubmed/20028970" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D044767" ]

[ "HGF-induced activation of c-Met is playing a pivotal role in the stimulation of c-Src activation, resulting in induction of phosphatidylinositol 3-kinase complexes p85α/p110α and p85α/p110δ, which is required for Akt-mediated activation of mammalian target of rapamycin, with consequent inhibition of IκB kinase and nuclear factor-κB activation, resulting in enhanced cell survival." ]

[ "yes" ]

[ "Amplification of MET has been reported in approximately 5%-22% of lung tumors with acquired resistance to small-molecule inhibitors of the epidermal growth factor receptor (EGFR). Resistance to EGFR inhibitors is likely mediated through downstream activation of the phosphoinositide 3-kinase /AKT pathway.", "Simultaneous treatment of resistant tumors with a MET inhibitor plus an EGFR inhibitor can abrogate activation of downstream effectors of cell growth, proliferation, and survival, thereby overcoming acquired resistance to EGFR inhibitors.", "HGF mediated both ERK and Akt phosphorylation.", "ERK/Akt signaling, but not the Smad pathway, may be one of the main processes in HGF-induced EMT,", "The MAPK/Akt pathway is indispensable in HGF/c-Met signaling.", "Inhibition of c-Met activation sensitizes osteosarcoma cells to cisplatin via suppression of the PI3K-Akt signaling", "Specifically, we demonstrated that inhibition of c-Met activity led to suppression of the PI3K-Akt pathway, thus enhancing cisplatin chemosensitivity.", "Our study clearly suggests that inhibition of c-Met activity can effectively sensitize osteosarcoma cells to cisplatin via suppression of the PI3K-Akt signaling.", "We found that a dual Met/VEGF receptor 2 kinase inhibitor, E7050, circumvented HGF-induced EGFR-TKI resistance in EGFR mutant lung cancer cell lines by inhibiting the Met/Gab1/PI3K/Akt pathway in vitro.", "Here, we report that i) treatment of RL95-2 cells with HGF resulted in phosphorylation of the HGF receptor c-Met, activation of Akt and IκB, translocation of NF-κB into the nucleus, and up-regulation of COX-2 mRNA;", "Our data suggest that HGF possesses chemotactic ability, has anti-apoptosis action, and induces cellular infiltration via the PI3K/Akt pathway;", "Hepatocyte growth factor-induced c-Src-phosphatidylinositol 3-kinase-AKT-mammalian target of rapamycin pathway inhibits dendritic cell activation by blocking IκB kinase activity", "Activation of c-Src in turn establishes a complex consisting of phosphatidylinositol 3-kinase and c-MET, and promotes downstream activation of the phosphatidylinositol 3-kinase/AKT pathway and mammalian target of rapamycin.", "Notably, hepatocyte growth factor-stimulated c-Src activation results in induction of phosphatidylinositol 3-kinase complexes p85α/p110α and p85α/p110δ, which is required for activation of mammalian target of rapamycin, and consequent inhibition of IκB kinase and nuclear factor-κB activation.", "Our findings, for the first time, have identified the c-Src-phosphatidylinositol 3-kinase-AKT-mammalian target of rapamycin pathway that plays a pivotal role in mediating the inhibitory effects of hepatocyte growth factor on dendritic cell activation by blocking nuclear factor-κB signaling.", "Cyr61 siRNA inhibited a second phase of Akt phosphorylation measured 12 hours after cell stimulation with HGF and also inhibited HGF-induced phosphorylation of the Akt target glycogen synthase kinase 3alpha.", "HGF+EGF treatment increased the duration of ERK1/2 and AKT activation compared to HGF or EGF alone. All these data indicate that a crosstalk between the EGF and HGF pathways in mammary epithelial cells may modulate the development of the mammary gland.", "Hepatocyte growth factor and c-Met promote dendritic maturation during hippocampal neuron differentiation via the Akt pathway", "Consistent with these results, HGF activated Akt, which phosphorylates glycogen synthase kinase-3beta (GSK-3beta) to inactivate it, and reduced phosphorylation of microtubule-associated protein 2 (MAP2), which can promote microtubule polymerization and dendrite elongation when dephosphorylated.", "Conversely, pharmacological inhibition of c-Met with its specific inhibitor, PHA-665752, or genetic knock-down of c-Met with short hairpin RNAs (shRNAs) suppressed HGF-induced phosphorylation of Akt and GSK-3beta, increased phosphorylation of MAP2, and reduced dendrite number and length in cultured hippocampal neurons.", "Inhibiting Akt activity with the phosphoinositide-3-kinase inhibitor LY294002 or Akt inhibitor X suppressed HGF-induced phosphorylation of GSK-3beta, increased MAP2 phosphorylation, and blocked the ability of HGF to enhance dendritic length.", "These observations indicate that HGF and c-Met can regulate the early stages of dendrite maturation via activation of the Akt/GSK-3beta pathway.", "Involvement of PI3K/Akt signaling pathway in hepatocyte growth factor-induced migration of uveal melanoma cells", "HGF was found to enhance cell migration, and that HGF-induced migration depends on PI3K/Akt pathway. The activation of PI3K/Akt pathway induced by the HGF/c-Met axis is involved in the downregulation of cell adhesion molecules E-cadherin and beta-catenin, contributing to the attenuation of cell-cell adhesion and promoting the enhanced motility and migration of uveal melanoma cells.", "HGF protects cultured cortical neurons against hypoxia/reoxygenation induced cell injury via ERK1/2 and PI-3K/Akt pathways", "HGF stimulated both ERK1/2 and Akt activities in cortical neurons.", "Inhibition of ERK activation completely abolished the protective effects of HGF, and inhibition of Akt activation reduced, but did not completely eliminate the HGF mediated neuroprotection.", "It is suggested that the neuroprotection of HGF depend on ERK1/2 pathway, and, to a lesser extent, PI-3K/Akt pathway. ", "Met signals hepatocyte survival by preventing Fas-triggered FLIP degradation in a PI3k-Akt-dependent manner", "Thus, Met acting on PI3K and Akt ensures high levels of FLIPL, and disruption of this pathway contributes to hepatic apoptosis and possibly to Fas-related liver diseases.", "The HGF-induced increase in Nkx 2.5 expression was inhibited by co-treatment with the PI3 kinase inhibitors Wortmannin and LY294002, but not by its inactive homolog LY303511, suggesting an involvement of the PI3 kinase/Akt pathway in this effect.", "X-Linked inhibitor of apoptosis protein expression level in colorectal cancer is regulated by hepatocyte growth factor/C-met pathway via Akt signaling", "Activation of XIAP expression by HGF was inhibited by siRNA targeting Akt1 and Akt2.", "Activation of C-MET enhances XIAP through the Akt pathway.", "Hepatocyte growth factor prevents ventricular remodeling and dysfunction in mice via Akt pathway and angiogenesis", "A significant reduction in apoptosis in the HGF-treated hearts was observed compared with control hearts, and was strongly associated with increased Akt activation.", "The antiapoptotic effect of HGF was mediated by activation of PI3-kinase/Akt pathway.", "The protective effect of HGF/SF against the ADR-induced apoptosis was abolished in the presence of either LY294002, an inhibitor of phosphatidylinositol-3'-OH kinase (PI3-K) or 1L-6-hydroxymethyl-chiro-inositol 2-(R)-2-O-methyl-3-O-octadecylcarbonate, an inhibitor of Akt, thus implicating the activation of PI3-K-Akt signaling in the antiapoptotic action of HGF/SF.", "Immunoblotting analysis revealed that HGF/SF stimulated the sustained phosphorylation of Akt for several hours", "Furthermore, ADR-induced activation of caspase-9, a downstream molecule of Akt, was inhibited for at least 24 h after HGF/SF stimulation,", "These results indicate that HGF/SF, but not EGF, transmitted protective signals against ADR-induced apoptosis by causing sustained activation of the PI3-K-Akt signaling pathway.", "Hepatocyte growth factor/scatter factor inhibits UVB-induced apoptosis of human keratinocytes but not of keratinocyte-derived cell lines via the phosphatidylinositol 3-kinase/AKT pathway", "When we analyzed the signaling pathways initiated by the HGF/SF receptor c-met, we found that the phosphatidylinositol (PI) 3-kinase and its downstream-element AKT and the mitogen-activated protein (MAP) kinase were activated.", "Inhibition of PI 3-kinase led to a complete abrogation of the anti-apoptotic effect of HGF/SF, whereas blockade of the MAP kinase pathway had no effect.", "We now show in detached cells a cooperative effect of HGF and FN in the activation of PI 3-kinase and on the phosphorylation of PKB/Akt at serine 473.", "PI 3-kinase activity is also required for the HGF- and fibronectin-induced survival responses, as well as anchorage-independent colony growth.", "Together, these results demonstrate that the PI 3-kinase/Akt pathway is a key effector of the HGF- and fibronectin-induced survival response of breast carcinoma cells under detached conditions and corroborate an interaction between integrin and HGF/ Met signalling pathways in the development of invasive breast cancer." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/17258200", "http://www.ncbi.nlm.nih.gov/pubmed/23345546", "http://www.ncbi.nlm.nih.gov/pubmed/14570904", "http://www.ncbi.nlm.nih.gov/pubmed/18234991", "http://www.ncbi.nlm.nih.gov/pubmed/22820099", "http://www.ncbi.nlm.nih.gov/pubmed/23229794", "http://www.ncbi.nlm.nih.gov/pubmed/21687953", "http://www.ncbi.nlm.nih.gov/pubmed/17942284", "http://www.ncbi.nlm.nih.gov/pubmed/15522281", "http://www.ncbi.nlm.nih.gov/pubmed/10714768", "http://www.ncbi.nlm.nih.gov/pubmed/19850646", "http://www.ncbi.nlm.nih.gov/pubmed/21536148", "http://www.ncbi.nlm.nih.gov/pubmed/11821397", "http://www.ncbi.nlm.nih.gov/pubmed/18262389", "http://www.ncbi.nlm.nih.gov/pubmed/20233866", "http://www.ncbi.nlm.nih.gov/pubmed/22789825", "http://www.ncbi.nlm.nih.gov/pubmed/16278380", "http://www.ncbi.nlm.nih.gov/pubmed/17464994" ]

[]

[ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0043491", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0048012", "http://www.uniprot.org/uniprot/SLTM_HUMAN", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D051057", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D019859", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0051896", "http://www.uniprot.org/uniprot/AKT1_HUMAN" ]

[ "Pregnant women are at increased risk for complications from pandemic influenza H1N1 virus infection. Pregnant women, because of their altered immunity and physiological adaptations, are at higher risk of developing pulmonary complications, especially in the second and third trimesters. Pregnancy, particularly during the third trimester, increases the risk of complications and early antiviral treatment is associated with improved outcomes." ]

[ "yes" ]

[ "H1N1 influenza in pregnancy can be associated with severe complications", "This case series confirms a high number of complications in pregnant women due to pandemic H1N1/09.", "Pregnant women might be at increased risk for complications from pandemic H1N1 virus infection.", "Pregnant women are at increased risk for complications from pandemic influenza H1N1 virus infection. ", "Vaccination of pregnant women against influenza A (H1N1) by Russian subunit formulation (MonoGrippol plus) showed reactogenicity comparable to control group by the level of influence on general metabolic and immunologic homeostasis and on the course of pregnancy, which is an evidence of its safety", "Pregnancy was identified as a major risk factor for increased mortality and morbidity due to H1N1 influenza in the pandemic of 2009 to 2010", "While it is not possible to ascertain retrospectively if myocarditis was caused by either infection with H1N1 virus or as a result of pregnancy (in the absence of endomyocardial biopsies), the significant association with myocardial involvement in both women demonstrates the increased risk of exposure to H1N1 influenza virus in pregnant women.", "Although limited in size, the fully prospective nature of the safety follow-up of these women vaccinated during pregnancy is unique and offers an important degree of reassurance for the use of the AS03 adjuvanted H1N1 (2009) vaccine in this high risk group for H1N1 infection.", "During the H1N1 2009 pandemic, pregnant women constituted one of the priority groups for vaccination in many countries, creating a need for close monitoring of the safety of the vaccine in pregnant women", "Emerging data suggest that pregnancy conveys high risk for severe complications from the 2009 pandemic influenza A virus (2009 H1N1) infection", "Pregnant women have been identified as a group at risk, both for respiratory complications than for the admissions to the Intensive Care Unit (ICU) during the 2009 H1N1 influenza pandemic", "This report mitigates substantially the presumed severity of pandemic H1N1/09 influenza infection during pregnancy", "The results of our study do not indicate a risk for the pregnant woman and the developing embryo/fetus after H1N1 vaccination", "This large cohort study found no evidence of an increased risk of fetal death associated with exposure to an adjuvanted pandemic A/H1N1 2009 influenza vaccine during pregnancy", "Our results suggest that second- or third-trimester H1N1 vaccination was associated with improved fetal and neonatal outcomes during the recent pandemic", "Pregnant women might thus be at increased risk of complications from pandemic H1N1 virus infection, and illness may progress rapidly", "Pregnant women with H1N1 infection seem to benefit from antiviral therapy.", "arly identification and treatment were the most important factors in different countries and areas examined.", "The vaccine and antiviral drugs that have been the most efficient means to control the novel virus appear to be safe but require more extensive study", "However, there were significant differences between the two groups in relation to mean age, treatment with oseltamivir, schooling, and presence of other risk factors", "To investigate whether exposure to an adjuvanted influenza A(H1N1)pdm09 vaccine during pregnancy was associated with increased risk of adverse fetal outcomes.", "In this Danish cohort, exposure to an adjuvanted influenza A(H1N1)pdm09 vaccine during pregnancy was not associated with a significantly increased risk of major birth defects, preterm birth, or fetal growth restriction", "Most people affected by the virus, including pregnant women, suffer a mild viral illness, and make a full recovery", "Pregnant women, because of their altered immunity and physiological adaptations, are at higher risk of developing pulmonary complications, especially in the second and third trimesters", "The pregnancy outcomes were also poor for women who were affected by the virus with a fivefold increase in the perinatal mortality rate and threefold increase in the preterm delivery rate", "regnant women were at increased risk for serious outcomes of 2009 pandemic influenza A virus subtype H1N1 (influenza A[H1N1]pdm09) infection, but little is known about the overall impact of the pandemic on neonatal and maternal outcomes", "In this large, geographically diverse population, A(H1N1)pdm09 infection increased the risk for hospitalization during pregnancy", "Vaccination during pregnancy with Pandemrix(®) appeared to have no ill effects on the pregnancy. On the contrary, the rate of preterm birth and low birthweight was lower than expected, which agrees with some previous results", "During the influenza A(H1N1)pmd09 pandemic, although many cases occurred in younger adults, the risk factors identified for severe infections and complications were similar to those for seasonal influenza, including chronic respiratory, renal, liver, and heart diseases.", "In terms of pregnancy, the studies have shown contradictory results due to variations in methodology and medical care.", "However, it seems that pregnancy, particularly during the third trimester, increases the risk of complications, and that early antiviral treatment is associated with improved outcomes.", "Pregnant women with mild clinical illness secondary to 2009 H1N1 were not at a greater risk of adverse pregnancy outcomes", "However, severely infected women were more likely to deliver SGA infants", "Gestational age is associated with the risk of developing critical infection. The risk increases with increasing weeks of gestation.", " Following the start of winter in Liaoning province in China, the number of pregnant women infected with influenza increased significantly", "regnancy, with or without additional complications, constitutes a high-risk condition for complications of influenza infection and warrants early intervention with neuraminidase inhibitors such as oseltamivir, if influenza is suspected" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/22551713", "http://www.ncbi.nlm.nih.gov/pubmed/22782418", "http://www.ncbi.nlm.nih.gov/pubmed/22482974", "http://www.ncbi.nlm.nih.gov/pubmed/22851818", "http://www.ncbi.nlm.nih.gov/pubmed/20148081", "http://www.ncbi.nlm.nih.gov/pubmed/24051575", "http://www.ncbi.nlm.nih.gov/pubmed/22515877", "http://www.ncbi.nlm.nih.gov/pubmed/22859826", "http://www.ncbi.nlm.nih.gov/pubmed/22331165", "http://www.ncbi.nlm.nih.gov/pubmed/22564554", "http://www.ncbi.nlm.nih.gov/pubmed/21596080", "http://www.ncbi.nlm.nih.gov/pubmed/21756329", "http://www.ncbi.nlm.nih.gov/pubmed/20531946", "http://www.ncbi.nlm.nih.gov/pubmed/20100064", "http://www.ncbi.nlm.nih.gov/pubmed/21913391", "http://www.ncbi.nlm.nih.gov/pubmed/22411229", "http://www.ncbi.nlm.nih.gov/pubmed/19643469", "http://www.ncbi.nlm.nih.gov/pubmed/21252793", "http://www.ncbi.nlm.nih.gov/pubmed/22030045", "http://www.ncbi.nlm.nih.gov/pubmed/23116790", "http://www.ncbi.nlm.nih.gov/pubmed/22272853", "http://www.ncbi.nlm.nih.gov/pubmed/22120858" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D018566", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D053118", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012306", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011247" ]

[ "Based on results no crustal structure of Greek Goat Encephalitis found." ]

[ "no" ]

[]

[ "http://www.ncbi.nlm.nih.gov/pubmed/20862256", "http://www.ncbi.nlm.nih.gov/pubmed/18258134", "http://www.ncbi.nlm.nih.gov/pubmed/18471057" ]

[ { "p": "http://www.w3.org/2000/01/rdf-schema#subClassOf", "s": "http://purl.uniprot.org/taxonomy/41406", "o": "http://purl.uniprot.org/taxonomy/39686" }, { "p": "http://purl.uniprot.org/core/scientificName", "s": "http://purl.uniprot.org/taxonomy/39686", "o": "unclassified Flavivirus" }, { "p": "http://purl.uniprot.org/core/scientificName", "s": "http://purl.uniprot.org/taxonomy/41406", "o": "Greek goat encephalitis virus" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A2147701", "o": "41406" }, { "p": "http://linkedlifedata.com/resource/umls/prefMetaMap", "s": "http://linkedlifedata.com/resource/umls/id/C1009477", "o": "http://linkedlifedata.com/resource/umls/label/A2147701" }, { "p": "http://www.w3.org/2008/05/skos-xl#prefLabel", "s": "http://linkedlifedata.com/resource/umls/id/C1009477", "o": "http://linkedlifedata.com/resource/umls/label/A2147701" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A2147701", "o": "Greek goat encephalitis virus" } ]

[ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004660", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D003460", "http://www.disease-ontology.org/api/metadata/DOID:646", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D015511", "http://www.disease-ontology.org/api/metadata/DOID:9588" ]

[ "No. Most long non coding RNAs (lncRNAs) are under lower sequence constraints than protein-coding genes." ]

[ "no" ]

[ "Most lncRNAs are under lower sequence constraints than protein-coding genes and lack conserved secondary structures, making it hard to predict them computationally.", "hey are under stronger selective pressure than neutrally evolving sequences-particularly in their promoter regions, which display levels of selection comparable to protein-coding genes.", "bout one-third seem to have arisen within the primate lineage." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/23467124", "http://www.ncbi.nlm.nih.gov/pubmed/22955988", "http://www.ncbi.nlm.nih.gov/pubmed/22707570", "http://www.ncbi.nlm.nih.gov/pubmed/22844254", "http://www.ncbi.nlm.nih.gov/pubmed/22708672", "http://www.ncbi.nlm.nih.gov/pubmed/23463798", "http://www.ncbi.nlm.nih.gov/pubmed/23028352", "http://www.ncbi.nlm.nih.gov/pubmed/20428234", "http://www.ncbi.nlm.nih.gov/pubmed/20624288", "http://www.ncbi.nlm.nih.gov/pubmed/21112873", "http://www.ncbi.nlm.nih.gov/pubmed/21622663", "http://www.ncbi.nlm.nih.gov/pubmed/20587619", "http://www.ncbi.nlm.nih.gov/pubmed/23454638" ]

[]

[]

[ "Brain-lung-thyroid syndrome (BLTS) characterized by congenital hypothyroidism, respiratory distress syndrome, and benign hereditary chorea is caused by thyroid transcription factor 1 (NKX2-1/TTF1) mutations." ]

[ "thyroid transcription factor 1" ]

[ " The disorder is caused by mutations to the NKX2.1 (TITF1) gene and also forms part of the \"brain-lung-thyroid syndrome\", in which additional developmental abnormalities of lung and thyroid tissue are observed. ", "Novel NKX2-1 Frameshift Mutations in Patients with Atypical Phenotypes of the Brain-Lung-Thyroid Syndrome.", "OBJECTIVES: To verify the involvement of NKX2-1 gene in infants with brain-lung-thyroid (BLT) syndrome and hypothyroid phenotypes variable among congenital hypothyroidism (CH) or idiopathic mild hypothyroidism (IMH) of postnatal onset.", "They were carriers of new de novo heterozygous frameshift mutations of NKX2-1 (c.177delG and c.153_166del14).", "CONCLUSIONS: Two novel heterozygous frameshift mutations of NKX2-1 were identified in 2 cases selected on the basis of a BLT-like phenotype among 183 hypothyroid infants. ", "NKX2-1 mutations in brain-lung-thyroid syndrome: a case series of four patients.", "Brain-lung-thyroid syndrome (BLTS) characterized by congenital hypothyroidism, respiratory distress syndrome, and benign hereditary chorea is caused by thyroid transcription factor 1 (NKX2-1/TTF1) mutations.", "Two of the four patients presenting with the triad of BLTS had NKX2-1 mutations, and one of these NKX2-1 [c.890_896del (p.Ala327Glyfs*52)] is a novel variant. The third patient without any identified NKX2-1 mutations was a carrier of mitochondrial mutation; this raises the possibility of mitochondrial mutations contributing to thyroid dysgenesis. Although rare, the triad of congenital hypothyroidism, neurological, and respiratory signs is highly suggestive of NKX2-1 anomalies. Screening for NKX2-1 mutations in patients with thyroid, lung, and neurological abnormalities will enable a unifying diagnosis and genetic counseling for the affected families. In addition, identification of an NKX2-1 defect would be helpful in allaying the concerns about inadequate thyroxine supplementation as the cause of neurological defects observed in some children with congenital hypothyroidism.", "Loss-of-function mutations in NKX2.1, a gene vital to the normal development and function of the brain, lungs, and thyroid, have been identified in a number of individuals.", "BACKGROUND: NKX2.1 mutations have been identified in patients displaying complete or partial brain-lung-thyroid syndrome, which can include benign hereditary chorea (BHC), hypothyroidism and/or lung disease.", "CONCLUSION: MLPA should be considered as a complementary tool in patients with partial or total brain-lung-thyroid syndrome when direct sequencing failed to identify NKX2.1 mutations. ", "Mutations in NKX2-1 cause neurological, pulmonary, and thyroid hormone impairment. Recently, the disease was named brain-lung-thyroid syndrome. ", "Genetic analysis of NKX2-1 revealed a novel missense mutation (p.Val205Phe) in two patients who were cousins and their maternal families, and a novel 2.6-Mb deletion including NKX2-1 on chromosome 14 in the other patient. Congenital hypothyroidism was not detected on neonatal screening in the patient with the missense mutation, and frequent respiratory infections were observed in the patient with the deletion in NKX2-1. ", "Haploinsufficiency of NKX2.1, the gene encoding the thyroid transcription factor-1 (TTF-1)--critical for lung, thyroid and central nervous system morphogenesis and function--causes a rare form of progressive respiratory failure designated brain-lung-thyroid syndrome. ", "We report a novel TTF-1 molecular defect causing recurrent respiratory failure episodes in an infant.", "In conclusion, ILD in patients with NKX2-1 mutations was associated with altered surfactant protein metabolism, and both gain and loss of function of the mutated NKX2-1 genes on surfactant protein promoters were associated with ILD in \"Brain-Lung-Thyroid syndrome\".", "Thyroid transcription factor 1 (NKX2-1/TITF1) mutations cause brain-lung-thyroid syndrome, characterized by congenital hypothyroidism (CH), infant respiratory distress syndrome (IRDS) and benign hereditary chorea (BHC).", "The objectives of the present study were (i) detection of NKX2-1 mutations in patients with CH associated with pneumopathy and/or BHC, (ii) functional analysis of new mutations in vitro and (iii) description of the phenotypic spectrum of brain-lung-thyroid syndrome.", "Five new TTF1/NKX2.1 mutations in brain-lung-thyroid syndrome: rescue by PAX8 synergism in one case.", "NKX2-1 mutations leading to surfactant protein promoter dysregulation cause interstitial lung disease in \"Brain-Lung-Thyroid Syndrome\".", "Multiplex Ligation-dependent Probe Amplification improves the detection rate of NKX2.1 mutations in patients affected by brain-lung-thyroid syndrome.", "NKX2.1 mutations have been identified in patients displaying complete or partial brain-lung-thyroid syndrome, which can include benign hereditary chorea (BHC), hypothyroidism and/or lung disease.", "The clinical spectrum of 6 own and 40 published patients with NKX2-1 mutations ranged from the complete triad of brain-lung-thyroid syndrome (50%), brain and thyroid disease (30%), to isolated BHC (13%).", "Haploinsufficiency of NKX2.1, the gene encoding the thyroid transcription factor-1 (TTF-1)--critical for lung, thyroid and central nervous system morphogenesis and function--causes a rare form of progressive respiratory failure designated brain-lung-thyroid syndrome.", "Thyroid transcription factor 1 (NKX2-1/TITF1) mutations cause brain-lung-thyroid syndrome, characterized by congenital hypothyroidism (CH), infant respiratory distress syndrome (IRDS) and benign hereditary chorea (BHC). ", "The clinical spectrum of 6 own and 40 published patients with NKX2-1 mutations ranged from the complete triad of brain-lung-thyroid syndrome (50%), brain and thyroid disease (30%), to isolated BHC (13%). ", "In conclusion, ILD in patients with NKX2-1 mutations was associated with altered surfactant protein metabolism, and both gain and loss of function of the mutated NKX2-1 genes on surfactant protein promoters were associated with ILD in \"Brain-Lung-Thyroid syndrome\".", "BACKGROUND: NKX2.1 mutations have been identified in patients displaying complete or partial brain-lung-thyroid syndrome, which can include benign hereditary chorea (BHC), hypothyroidism and/or lung disease. ", "CONCLUSION: MLPA should be considered as a complementary tool in patients with partial or total brain-lung-thyroid syndrome when direct sequencing failed to identify NKX2.1 mutations. ", "Brain-lung-thyroid syndrome (BLTS) characterized by congenital hypothyroidism, respiratory distress syndrome, and benign hereditary chorea is caused by thyroid transcription factor 1 (NKX2-1/TTF1) mutations. ", "Thyroid transcription factor 1 (NKX2-1/TITF1) mutations cause brain-lung-thyroid syndrome, characterized by congenital hypothyroidism (CH), infant respiratory distress syndrome (IRDS) and benign hereditary chorea (BHC). The objectives of the present study were (i) detection of NKX2-1 mutations in patients with CH associated with pneumopathy and/or BHC, (ii) functional analysis of new mutations in vitro and (iii) description of the phenotypic spectrum of brain-lung-thyroid syndrome.", " Mutations of genes affecting surfactant homeostasis, such as SFTPB, SFTPC and ABCA3, lead to diffuse lung disease in neonates and children. Haploinsufficiency of NKX2.1, the gene encoding the thyroid transcription factor-1 (TTF-1)--critical for lung, thyroid and central nervous system morphogenesis and function--causes a rare form of progressive respiratory failure designated brain-lung-thyroid syndrome.", "The disorder is caused by mutations to the NKX2.1 (TITF1) gene and also forms part of the \"brain-lung-thyroid syndrome\", in which additional developmental abnormalities of lung and thyroid tissue are observed.", "Haploinsufficiency of NKX2.1, the gene encoding the thyroid transcription factor-1 (TTF-1)--critical for lung, thyroid and central nervous system morphogenesis and function--causes a rare form of progressive respiratory failure designated brain-lung-thyroid syndrome. Molecular mechanisms involved in this syndrome are heterogeneous and poorly explored.", "Brain-lung-thyroid syndrome (BLTS) characterized by congenital hypothyroidism, respiratory distress syndrome, and benign hereditary chorea is caused by thyroid transcription factor 1 (NKX2-1/TTF1) mutations.", "Haploinsufficiency of NKX2.1, the gene encoding the thyroid transcription factor-1 (TTF-1)--critical for lung, thyroid and central nervous system morphogenesis and function--causes a rare form of progressive respiratory failure designated brain-lung-thyroid syndrome.", "NKX2-1 mutations leading to surfactant protein promoter dysregulation cause interstitial lung disease in \"Brain-Lung-Thyroid Syndrome\".", "Thyroid transcription factor 1 (NKX2-1/TITF1) mutations cause brain-lung-thyroid syndrome, characterized by congenital hypothyroidism (CH), infant respiratory distress syndrome (IRDS) and benign hereditary chorea (BHC).", "NKX2-1 mutations in brain-lung-thyroid syndrome: a case series of four patients.", "Novel NKX2-1 Frameshift Mutations in Patients with Atypical Phenotypes of the Brain-Lung-Thyroid Syndrome.", "The clinical spectrum of 6 own and 40 published patients with NKX2-1 mutations ranged from the complete triad of brain-lung-thyroid syndrome (50%), brain and thyroid disease (30%), to isolated BHC (13%).", "Mutations in the gene encoding thyroid transcription factor, NKX2-1, result in neurologic abnormalities, hypothyroidism, and neonatal respiratory distress syndrome (RDS) that together are known as the brain-thyroid-lung syndrome." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/22166853", "http://www.ncbi.nlm.nih.gov/pubmed/20020530", "http://www.ncbi.nlm.nih.gov/pubmed/25759798", "http://www.ncbi.nlm.nih.gov/pubmed/26196025", "http://www.ncbi.nlm.nih.gov/pubmed/24129101", "http://www.ncbi.nlm.nih.gov/pubmed/22488412", "http://www.ncbi.nlm.nih.gov/pubmed/24171694", "http://www.ncbi.nlm.nih.gov/pubmed/23430038", "http://www.ncbi.nlm.nih.gov/pubmed/19336474", "http://www.ncbi.nlm.nih.gov/pubmed/21867529" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009154", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005796" ]

[ "Clathrin helps build small vesicles in order to safely transport molecules within and between cells." ]

[]

[ "Clathrin-mediated endocytosis is a central and well-studied trafficking process in eukaryotic cells.", "We reported the first small molecule inhibitors of the interaction between the clathrin N-terminal domain (TD) and endocyctic accessory proteins (i.e., clathrin inhibition1).", "Tubulobulbar complexes are elaborate clathrin/actin related structures that form at sites of intercellular attachment in the seminiferous epithelium of the mammalian testis.", " Clathrin-coated vesicles (CCVs) are formed at the plasma membrane and act as vectors for endocytosis. They also assemble at the trans-Golgi network (TGN), but their exact function at this organelle is unclear. ", " Clathrin immunohistochemistry and immunoblotting showed increased immunoreactivity of clathrin protein in the placental tissues of mice treated with 20- and 50-nm gold nanoparticles; clathrin immunopositivity was observed in syncytiotrophoblasts and fetal endothelial cells." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/24322426", "http://www.ncbi.nlm.nih.gov/pubmed/23093191", "http://www.ncbi.nlm.nih.gov/pubmed/19809570", "http://www.ncbi.nlm.nih.gov/pubmed/12952941", "http://www.ncbi.nlm.nih.gov/pubmed/22042622", "http://www.ncbi.nlm.nih.gov/pubmed/24307937", "http://www.ncbi.nlm.nih.gov/pubmed/24280271", "http://www.ncbi.nlm.nih.gov/pubmed/24299503", "http://www.ncbi.nlm.nih.gov/pubmed/24263003", "http://www.ncbi.nlm.nih.gov/pubmed/21445329", "http://www.ncbi.nlm.nih.gov/pubmed/24257253" ]

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[ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0030118", "http://www.uniprot.org/uniprot/CLCA_MOUSE", "http://www.uniprot.org/uniprot/CLCA_HUMAN", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D033922", "http://www.uniprot.org/uniprot/CLCA_BOVIN", "http://www.uniprot.org/uniprot/CLC1_SCHPO", "http://www.uniprot.org/uniprot/CLC_DICDI", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0030119", "http://www.uniprot.org/uniprot/CLC1_YEAST", "http://www.biosemantics.org/jochem#4250446", "http://www.uniprot.org/uniprot/EPN4_BOVIN", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D033942", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D033941", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0030276", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0071439", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D002966", "http://www.uniprot.org/uniprot/EPN4_MOUSE", "http://www.uniprot.org/uniprot/CLCA_RAT", "http://www.uniprot.org/uniprot/CLC_DROME" ]

[ "Suppression of protein kinase A regulatory subunit 1 alpha (PRKAR1A) has been proven to inhibit cholangiocarcinoma (CCA) cell growth and enhance apoptosis. Also, Knockdown of the cAMP-dependent protein kinase (PKA) Type Ialpha regulatory subunit in mouse oocytes disrupts meiotic arrest and results in meiotic spindle defects." ]

[]

[ "These results show that RIα inactivation leads to multiple, compartment-specific alterations of the cAMP/PKA pathway revealing new aspects of signaling dysregulation in tumorigenesis.", "Suppression of protein kinase A regulatory subunit 1 alpha (PRKAR1A) has been proven to inhibit cholangiocarcinoma (CCA) cell growth and enhance apoptosis.", "Silencing PRKAR1A expression induced growth inhibition and apoptosis of CCA cells, with an associated decrease in mitogen-activated protein kinases, PI3K/Akt, JAK/STAT and Wnt/β-catenin pathway signaling.", "The inhibition of PKA using a PKA inhibitor and cAMP analogs also led to a significant cell growth inhibition.", "abrogation of gene expression caused significant CCA cell growth inhibition, oncogenic signaling and coupled apoptosis induction", "Knockdown of the cAMP-dependent protein kinase (PKA) Type Ialpha regulatory subunit in mouse oocytes disrupts meiotic arrest and results in meiotic spindle defects.", "These results demonstrate that RIalpha is required for regulating PKA activity in maturing oocytes and that compensatory upregulation of RII does not occur." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/20824711", "http://www.ncbi.nlm.nih.gov/pubmed/24122441", "http://www.ncbi.nlm.nih.gov/pubmed/16937372", "http://www.ncbi.nlm.nih.gov/pubmed/23480756" ]

[]

[ "http://www.uniprot.org/uniprot/KAP0_BOVIN", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D055785" ]

[ "Transcutaneous electrical nerve stimulation is widely used in pain management" ]

[ "yes" ]

[ "Transcutaneous electrical nerve stimulation is widely used in pain management but its effectiveness depends on the stimulation being targeted appropriately", "hypoalgesic effects of transcutaneous electrical nerve stimulation upon experimentally induced ischaemic pain.", "The results of this study have provided evidence of the hypoalgesic effects of TENS upon experimental ischaemic pain which were found to be frequency specific with the lower frequency used here (4 Hz) demonstrating the only significant effect" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/7644247", "http://www.ncbi.nlm.nih.gov/pubmed/17333874" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D018710", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D010146", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D059350", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004561" ]

[ "yes", "Yes. RFECS is a random-forest based algorithm for enhancer identification from chromatin state. It integrates histone modification profiles for the identification of enhancers, and can be used to identify enhancers in a number of cell-types. RFECS not only leads to more accurate and precise prediction of enhancers than previous methods, but also helps identify the most informative and robust set of three chromatin marks for enhancer prediction." ]

[ "yes" ]

[ "RFECS: a random-forest based algorithm for enhancer identification from chromatin state.", "However, only a limited number of cell types or chromatin marks have previously been investigated for this purpose, leaving the question unanswered whether there exists an optimal set of histone modifications for enhancer prediction in different cell types. Here, we address this issue by exploring genome-wide profiles of 24 histone modifications in two distinct human cell types, embryonic stem cells and lung fibroblasts. We developed a Random-Forest based algorithm, RFECS (Random Forest based Enhancer identification from Chromatin States) to integrate histone modification profiles for identification of enhancers, and used it to identify enhancers in a number of cell-types. We show that RFECS not only leads to more accurate and precise prediction of enhancers than previous methods, but also helps identify the most informative and robust set of three chromatin marks for enhancer prediction.", "We developed a Random-Forest based algorithm, RFECS (Random Forest based Enhancer identification from Chromatin States) to integrate histone modification profiles for identification of enhancers, and used it to identify enhancers in a number of cell-types.", "Here, we address this issue by exploring genome-wide profiles of 24 histone modifications in two distinct human cell types, embryonic stem cells and lung fibroblasts. We developed a Random-Forest based algorithm, RFECS (Random Forest based Enhancer identification from Chromatin States) to integrate histone modification profiles for identification of enhancers, and used it to identify enhancers in a number of cell-types. ", "ChromaGenSVM selects optimum combinations of specific histone epigenetic marks to predict enhancers. ", "We developed a Random-Forest based algorithm, RFECS (Random Forest based Enhancer identification from Chromatin States) to integrate histone modification profiles for identification of enhancers, and used it to identify enhancers in a number of cell-types." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/23526891", "http://www.ncbi.nlm.nih.gov/pubmed/22328731" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D000465" ]

[ "Imetelstat sodium (GRN163L), is a 13-mer oligonucleotide N3'→P5' thio-phosphoramidate lipid conjugate, which represents the latest generation of telomerase inhibitors targeting the template region of the human functional telomerase RNA subunit. In preclinical trials, this compound has been found to inhibit telomerase activity in multiple cancer cell lines, as well as in vivo xenograft mouse models." ]

[ "Human Telomerase" ]

[ "Imetelstat (a telomerase antagonist) exerts off‑target effects on the cytoskeleton.", "imetelstat sodium (GRN163L), is a 13-mer oligonucleotide N3'→P5' thio-phosphoramidate lipid conjugate, which represents the latest generation of telomerase inhibitors targeting the template region of the human functional telomerase RNA (hTR) subunit. In preclinical trials, this compound has been found to inhibit telomerase activity in multiple cancer cell lines, as well as in vivo xenograft mouse models. ", "In addition to the inhibition of telomerase activity in cancer cell lines, GRN163L causes morphological cell rounding changes, independent of hTR expression or telomere length.", "We sought to evaluate the potential of the thio-phosphoramidate oligonucleotide inhibitor of telomerase, imetelstat, as a drug candidate for treatment of esophageal cancer. Our results showed that imetelstat inhibited telomerase activity in a dose-dependent manner in esophageal cancer cells", "Furthermore, long-term treatment with imetelstat decreased cell growth of esophageal cancer cells with different kinetics regarding telomere lengths", " Telomerase extension is less processive during the first few weeks following the reversal of long-term treatment with the telomerase inhibitor Imetelstat (GRN163L), a time when Cajal bodies fail to deliver telomerase RNA to telomeres.", "The role of telomerase as an immunotherapy, as a gene therapy approach using telomerase promoter driven oncolytic viruses and as a small oligonucleotide targeted therapy (Imetelstat) will be discussed", "We then tested the efficacy of the telomerase inhibitor Imetelstat on propagation and self-renewal capacity of TIC and normal stem cells in vitro and in vivo. R", "e telomerase inhibitor imetelstat depletes cancer stem cells in breast and pancreatic cancer cell lines", "In this study, we investigated the effects of imetelstat (GRN163L), a potent telomerase inhibitor, on both the bulk cancer cells and putative CSCs. When breast and pancreatic cancer cell lines were treated with imetelstat in vitro, telomerase activity in the bulk tumor cells and CSC subpopulations were inhibited.", "Telomerase activity is required for the maintenance of normal adult stem cells, and we examined the activity of the telomerase inhibitor imetelstat against MM CSC.", "Human MM CSC were isolated from cell lines and primary clinical specimens and treated with imetelstat, a specific inhibitor of the reverse transcriptase activity of telomerase. Two weeks of exposure to imetelstat resulted in a significant reduction in telomere length and the inhibition of clonogenic MM growth both in vitro and in vivo. ", "Short oligonucleotide N3'-->P5' thio-phosphoramidate conjugated to 5'-palmitoyl group, designated as GRN163L (Imetelstat), was recently introduced as a potent human telomerase inhibitor", "etelstat (GRN163L)--telomerase-based cancer therapy.", "Imetelstat (GRN163L) is a potent and specific telomerase inhibitor and so far the only drug of its class in clinical trials.", "e telomerase antagonist, imetelstat, efficiently targets glioblastoma tumor-initiating cells leading to decreased proliferation and tumor growth.", "The effects of a novel human telomerase antagonist, imetelstat, on primary human glioblastoma (GBM) tumor-initiating cells were investigated in vitro and in vivo. ", "Imetelstat treatment produced a dose-dependent inhibition of telomerase (IC(50) 0.45 micromol/L). Long-term imetelstat treatment led to progressive telomere shortening, reduced rates of proliferation, and eventually cell death in GBM tumor-initiating cells.", " We have found that prostate TICs have significant telomerase activity which is inhibited by imetelstat sodium (GRN163L), a new telomerase antagonist that is currently in Phase I/II clinical trials for several hematological and solid tumor malignancies. Prostate TICs telomeres were of similar average length to the telomeres of the main population of cells and significant telomere shortening was detected in prostate TICs as a result of imetelstat treatment. ", "Telomerase activation was countered by co-treatment with Imetelstat (GRN163L), a potent telomerase inhibitor." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/21208905", "http://www.ncbi.nlm.nih.gov/pubmed/23386830", "http://www.ncbi.nlm.nih.gov/pubmed/21549308", "http://www.ncbi.nlm.nih.gov/pubmed/23521791", "http://www.ncbi.nlm.nih.gov/pubmed/23558965", "http://www.ncbi.nlm.nih.gov/pubmed/23545855", "http://www.ncbi.nlm.nih.gov/pubmed/20072842", "http://www.ncbi.nlm.nih.gov/pubmed/21845093", "http://www.ncbi.nlm.nih.gov/pubmed/23467584", "http://www.ncbi.nlm.nih.gov/pubmed/20232321", "http://www.ncbi.nlm.nih.gov/pubmed/21332640", "http://www.ncbi.nlm.nih.gov/pubmed/22382179", "http://www.ncbi.nlm.nih.gov/pubmed/21062983", "http://www.ncbi.nlm.nih.gov/pubmed/23272238", "http://www.ncbi.nlm.nih.gov/pubmed/24327604", "http://www.ncbi.nlm.nih.gov/pubmed/23516479", "http://www.ncbi.nlm.nih.gov/pubmed/19908230", "http://www.ncbi.nlm.nih.gov/pubmed/23326372", "http://www.ncbi.nlm.nih.gov/pubmed/22870217", "http://www.ncbi.nlm.nih.gov/pubmed/20824134", "http://www.ncbi.nlm.nih.gov/pubmed/22906540", "http://www.ncbi.nlm.nih.gov/pubmed/20048334", "http://www.ncbi.nlm.nih.gov/pubmed/23727752" ]

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[ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004798", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004791", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004358" ]

[ "Dupilumab, a fully human monoclonal antibody that blocks interleukin-4 and interleukin-13, has shown efficacy in patients with asthma and elevated eosinophil levels." ]

[ "interleukin-4", "interleukin-13" ]

[ "The world's first prospective controlled studies with the biologic human anti-IL4R antibody dupilumab for the indication \"atopic dermatitis\" were published in 2014. These motivated (1) to extend the studies to dupilumab and (2) to clinically test antagonization of other target molecules of TH2 polarized, atopic inflammation, e.g., IL-13, IL-31, IL-22, TSLP, and CRTH2. A", "Among the recently developed antiasthma biologic drugs, the monoclonal antibody dupilumab is very promising because of its ability to inhibit the biological effects of both IL-4 and IL-13. Indeed, dupilumab prevents IL-4/13 interactions with the α-subunit of the IL-4 receptor complex. ", "BACKGROUND: Dupilumab, a fully human monoclonal antibody that blocks interleukin-4 and interleukin-13, has shown efficacy in patients with asthma and elevated eosinophil levels. ", " In early-phase trials, dupilumab, a fully human mAb targeting IL-4 receptor α, markedly improved disease activity, but the effect of IL-4/IL-13 blockade on AD at the molecular level has not been characterized.", "Examples include the efficacy of omalizumab in patients with severe refractory atopic asthma characterized by raised serum total IgE, mepolizumab, reslizumab, and benralizumab in patients with recurrent eosinophilic exacerbations characterized by blood and sputum eosinophilia despite high doses of corticosteroids, and lebrikizumab, pitrakinra, dupilumab, and tralokinumab that target the IL-4/IL-13 signalling pathways in patients with eosinophilic asthma or raised serum periostin.", "BACKGROUND: Moderate-to-severe asthma remains poorly treated. We evaluated the efficacy and safety of dupilumab (SAR231893/REGN668), a fully human monoclonal antibody to the alpha subunit of the interleukin-4 receptor, in patients with persistent, moderate-to-severe asthma and elevated eosinophil levels.", "With respect to immune dysregulation, dupilumab, a fully human monoclonal antibody directed at the IL-4 receptor alpha subunit was recently shown to be effective in treating adults with moderate-to-severe AD.", "Dupilumab, a fully human monoclonal antibody that blocks interleukin-4 and interleukin-13, has shown efficacy in patients with asthma and elevated eosinophil levels.", "We evaluated the efficacy and safety of dupilumab (SAR231893/REGN668), a fully human monoclonal antibody to the alpha subunit of the interleukin-4 receptor, in patients with persistent, moderate-to-severe asthma and elevated eosinophil levels.", "Indeed, dupilumab prevents IL-4/13 interactions with the α-subunit of the IL-4 receptor complex.", "We evaluated the efficacy and safety of dupilumab (SAR231893/REGN668), a fully human monoclonal antibody to the alpha subunit of the interleukin-4 receptor, in patients with persistent, moderate-to-severe asthma and elevated eosinophil levels. ", "BACKGROUND: Dupilumab, a fully human monoclonal antibody that blocks interleukin-4 and interleukin-13, has shown efficacy in patients with asthma and elevated eosinophil levels. The blockade by dupilumab of these key drivers of type 2 helper T-cell (Th2)-mediated inflammation could help in the treatment of related diseases, including atopic dermatitis. ", "Indeed, dupilumab prevents IL-4/13 interactions with the α-subunit of the IL-4 receptor complex.", "We evaluated the efficacy and safety of dupilumab (SAR231893/REGN668), a fully human monoclonal antibody to the alpha subunit of the interleukin-4 receptor, in patients with persistent, moderate-to-severe asthma and elevated eosinophil levels.", "Dupilumab, a fully human monoclonal antibody that blocks interleukin-4 and interleukin-13, has shown efficacy in patients with asthma and elevated eosinophil levels." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/25482871", "http://www.ncbi.nlm.nih.gov/pubmed/25584909", "http://www.ncbi.nlm.nih.gov/pubmed/25006719", "http://www.ncbi.nlm.nih.gov/pubmed/25214796", "http://www.ncbi.nlm.nih.gov/pubmed/25645542", "http://www.ncbi.nlm.nih.gov/pubmed/24275927", "http://www.ncbi.nlm.nih.gov/pubmed/23688323" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D007378" ]

[ "The genes that are most commonly linked to craniosynostoses are the members of the Fibroblast Growth Factor Receptor family FGFR3 and to a lesser extent FGFR1 and FGFR2. Some variants of the disease have been associated with the triplication of the MSX2 gene and mutations in NELL-1. NELL-1 is being regulated bu RUNX2, which has also been associated to cases of craniosynostosis. Other genes reported to have a role in the development of the disease are RECQL4, TWIST, SOX6 and GNAS." ]

[ "FGFR3", "FGFR2", "FGFR1", "MSX2", "NELL1", "RUNX2", "RECQL4", "TWIST", "SOX6", "GNAS" ]

[ "The FGFR3 P250R mutation was the single largest contributor (24%) to the genetic group", "FGFR3 P250R and FGFR2 exons IIIa/c) should be targeted to patients with coronal or multisuture synostoses", "GNAS, the gene for guanine nucleotide-binding protein, alpha-stimulating activity polypeptide (gene for PHP1A), identified a de novo heterozygous 3 bp in frame deletion predicting a deletion of the asparagine residue at position 377 (deltaN377", "craniosynostosis genes (FGFR2, FGFR3)", "Syndromic craniosynostosis due to complex chromosome 5 rearrangement and MSX2 gene triplication", "early fusion of cranial sutures commonly observed in the dup(5q) syndrome is caused by triplication of the MSX2 gene", "further evidence that extra copy of MSX2 gene leads to craniosynostosis", "Our results support the previous finding that distal 5q-trisomy together with an extra copy of the MSX2 gene leads to abnormal closure of sutures and craniosynostosis", "Craniosynostosis-associated gene nell-1 is regulated by runx2", "We studied the transcriptional regulation of NELL-1, a craniosynostosis-related gene", "Runx2 directly binds to the OSE2 elements and transactivates the human NELL-1 promoter. These results suggest that Nell-1 is likely a downstream target of Runx2", "The breakpoint on chromosome 11p15 disrupts the SOX6 gene, known to be involved in skeletal growth and differentiation processes", "SOX6 mutation screening of another 104 craniosynostosis patients revealed one missense mutation leading to the exchange of a highly conserved amino acid (p.D68N) in a single patient and his reportedly healthy mother", "Revisiting the craniosynostosis-radial ray hypoplasia association: Baller-Gerold syndrome caused by mutations in the RECQL4 gene", "Overexpression of Nell-1, a craniosynostosis-associated gene", "Mutations in five genes (FGFR1-, -2, -3, TWIST, and MSX2) causing craniosynostosis as the main clinical feature were described.", "One of the genes involved in craniosynostosis syndromes is the fibroblast growth factor receptor 2 (FGFR2) gene, a tyrosine kinase receptor gene", "Most mutations in Crouzon, Pfeiffer, and Apert syndromes are in the extracellular, third immunoglobulin-like domain and adjacent linker regions (exons IIIa and IIIc) of the fibroblast growth factor receptor 2 (FGFR2) gene", "Familial craniosynostosis due to Pro250Arg mutation in the fibroblast growth factor receptor 3 gene.", "Apert (Ap) syndrome is characterized by premature cranial suture ossification caused by fibroblast growth factor receptor 2 (FGFR-2) mutations", "Recently, the substitution of proline 250 by arginine in the fibroblast growth factor receptor 3 (FGFR3) gene, has been identified in patients with craniosynostosis and defines a new syndrome on a molecular basis", "Mutations in the fibroblast growth factor receptor 1, 2 and 3 (FGFR1, -2 and -3) and TWIST genes have been identified in several syndromic forms of craniosynostosis", "We describe a novel heterozygous mutation of FGFR2 (943G --> T, encoding the amino acid substitution Ala315Ser) in a girl with non-syndromic unicoronal craniosynostosis.", "A unique Pro250Arg mutation in fibroblast growth factor receptor 3 (FGFR3) was recently found in patients with non-syndromic craniosynostosis", "a possible mechanism for MSX2-mediated craniosynostosis in humans", "We found previously that a single amino acid substitution in the homeodomain of the human MSX2 gene is associated with the autosomal dominant disorder craniosynostosis, Boston type.", "Recently, a unique Pro250Arg point mutation in fibroblast growth factor receptor 3 (FGFR3) was reported in 61 individuals with coronal craniosynostosis from 20 unrelated families", "We identified a novel TWIST gene mutation in this patient, a Glu181Stop mutation predicting a premature termination of the protein carboxy-terminal to the helix 2 domain", "A unique point mutation in the fibroblast growth factor receptor 3 gene (FGFR3) defines a new craniosynostosis syndrome", "A mutation in the homeodomain of the human MSX2 gene in a family affected with autosomal dominant craniosynostosis" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/12407713", "http://www.ncbi.nlm.nih.gov/pubmed/19530187", "http://www.ncbi.nlm.nih.gov/pubmed/16258006", "http://www.ncbi.nlm.nih.gov/pubmed/20643727", "http://www.ncbi.nlm.nih.gov/pubmed/10914960", "http://www.ncbi.nlm.nih.gov/pubmed/9934984", "http://www.ncbi.nlm.nih.gov/pubmed/18000908", "http://www.ncbi.nlm.nih.gov/pubmed/11428324", "http://www.ncbi.nlm.nih.gov/pubmed/17042739", "http://www.ncbi.nlm.nih.gov/pubmed/11746040", "http://www.ncbi.nlm.nih.gov/pubmed/17955513", "http://www.ncbi.nlm.nih.gov/pubmed/14672347", "http://www.ncbi.nlm.nih.gov/pubmed/10951518", "http://www.ncbi.nlm.nih.gov/pubmed/9917362", "http://www.ncbi.nlm.nih.gov/pubmed/15964893", "http://www.ncbi.nlm.nih.gov/pubmed/9042914", "http://www.ncbi.nlm.nih.gov/pubmed/11820058", "http://www.ncbi.nlm.nih.gov/pubmed/8106171", "http://www.ncbi.nlm.nih.gov/pubmed/9600744", "http://www.ncbi.nlm.nih.gov/pubmed/11484208", "http://www.ncbi.nlm.nih.gov/pubmed/11197897", "http://www.ncbi.nlm.nih.gov/pubmed/11341328" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D018566", "http://www.disease-ontology.org/api/metadata/DOID:2340", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D003398" ]

[ "Yes, it appears that there is widespread T-UCR (Transcribed - UltraConserved Region) involvement in diverse cellular processes that are deregulated in the process of tumourigenesis. Transcribed ultraconserved regions (T-UCRs) are a subset of 481 sequences longer than 200 bp, which are absolutely conserved between orthologous regions of human, rat and mouse genomes, and are actively transcribed. It has recently been proven in cancer systems that differentially expressed T-UCRs could alter the functional characteristics of malignant cells." ]

[ "yes" ]

[ "Although most cancer research has focused in mRNA, non-coding RNAs are also an essential player in tumorigenesis. In addition to the well-recognized microRNAs, recent studies have also shown that epigenetic silencing by CpG island hypermethylation of other classes of non-coding RNAs, such as transcribed ultraconserved regions (T-UCRs) or small nucleolar RNAs (snoRNAs), also occur in human neoplasia", "Starting from a genome-wide expression profiling, we demonstrate for the first time a functional link between oxygen deprivation and the modulation of long noncoding transcripts from ultraconserved regions, termed transcribed-ultraconserved regions (T-UCRs). Interestingly, several hypoxia-upregulated T-UCRs, henceforth named 'hypoxia-induced noncoding ultraconserved transcripts' (HINCUTs), are also overexpressed in clinical samples from colon cancer patients", "Consistent with the hypothesis that T-UCRs have important function in tumor formation", "The importance of other classes of non-coding RNAs, such as long intergenic ncRNAs (lincRNAs) and transcribed ultraconserved regions (T-UCRs) as altered elements in neoplasia, is also gaining recognition", "Expression levels of transcribed ultraconserved regions uc.73 and uc.388 are altered in colorectal cancer", "Transcribed ultraconserved regions (T-UCRs) are a subset of 481 sequences longer than 200 bp, which are absolutely conserved between orthologous regions of human, rat and mouse genomes, and are actively transcribed. It has recently been proven in cancer systems that differentially expressed T-UCRs could alter the functional characteristics of malignant cells. Genome-wide profiling revealed that T-UCRs have distinct signatures in human leukemia and carcinoma", " Our preliminary results suggest that uc.73 and uc.388 could be potential diagnostic and prognostic biomarkers in CRC patients", "The transcribed-ultraconserved regions: a novel class of long noncoding RNAs involved in cancer susceptibility", "This review gives a picture of the state of the art of a novel class of long ncRNA known as transcribed-ultraconserved regions (T-UCRs). Most recent studies show that they are significantly altered in adult chronic lymphocytic leukemias, carcinomas, and pediatric neuroblastomas, leading to the hypothesis that UCRs may play a role in tumorigenesis and promising innovative future T-UCR-based therapeutic approaches", "CpG island hypermethylation-associated silencing of non-coding RNAs transcribed from ultraconserved regions in human cancer", "We focused on the transcribed-ultraconserved regions (T-UCRs), a subset of DNA sequences that are absolutely conserved between orthologous regions of the human, rat and mouse genomes and that are located in both intra- and intergenic regions. We used a pharmacological and genomic approach to reveal the possible existence of an aberrant epigenetic silencing pattern of T-UCRs by treating cancer cells with a DNA-demethylating agent followed by hybridization to an expression microarray containing these sequences. We observed that DNA hypomethylation induces release of T-UCR silencing in cancer cells. Among the T-UCRs that were reactivated upon drug treatment, Uc.160+, Uc283+A and Uc.346+ were found to undergo specific CpG island hypermethylation-associated silencing in cancer cells compared with normal tissues. The analysis of a large set of primary human tumors (n=283) demonstrated that hypermethylation of the described T-UCR CpG islands was a common event among the various tumor types. Our finding that, in addition to microRNAs, another class of ncRNAs (T-UCRs) undergoes DNA methylation-associated inactivation in transformed cells supports a model in which epigenetic and genetic alterations in coding and non-coding sequences cooperate in human tumorigenesis", "An integrative genomics screen uncovers ncRNA T-UCR functions in neuroblastoma tumours", "Different classes of non-coding RNAs, including microRNAs, have recently been implicated in the process of tumourigenesis. In this study, we examined the expression and putative functions of a novel class of non-coding RNAs known as transcribed ultraconserved regions (T-UCRs) in neuroblastoma", "our results define a T-UCR expression landscape in neuroblastoma and suggest widespread T-UCR involvement in diverse cellular processes that are deregulated in the process of tumourigenesis", "Moreover, the recent demonstration that other ncRNAs, the ultraconserved genes (UCGs) or transcribed ultraconserved regions (T-UCRs), are involved in human cancerogenesis, suggests that the wider family of ncRNAs (including both miRNAs and UCGs) could contribute to the development of the malignant phenotype. Here we review the main studies investigating the role of miRNAs and UCRs in both normal hemopoiesis and hematological malignancies, and identify the molecular, clinical and therapeutic implications of these recent findings", "The transcribed-ultraconserved regions: a novel class of long noncoding RNAs involved in cancer susceptibility.", "Expression levels of transcribed ultraconserved regions uc.73 and uc.388 are altered in colorectal cancer.", "CpG island hypermethylation-associated silencing of non-coding RNAs transcribed from ultraconserved regions in human cancer.", "Starting from a genome-wide expression profiling, we demonstrate for the first time a functional link between oxygen deprivation and the modulation of long noncoding transcripts from ultraconserved regions, termed transcribed-ultraconserved regions (T-UCRs).", "The importance of other classes of non-coding RNAs, such as long intergenic ncRNAs (lincRNAs) and transcribed ultraconserved regions (T-UCRs) as altered elements in neoplasia, is also gaining recognition.", "Moreover, the recent demonstration that other ncRNAs, the ultraconserved genes (UCGs) or transcribed ultraconserved regions (T-UCRs), are involved in human cancerogenesis, suggests that the wider family of ncRNAs (including both miRNAs and UCGs) could contribute to the development of the malignant phenotype.", "Moreover, the recent demonstration that other ncRNAs, the ultraconserved genes (UCGs) or transcribed ultraconserved regions (T-UCRs), are involved in human cancerogenesis, suggests that the wider family of ncRNAs (including both miRNAs and UCGs) could contribute to the development of the malignant phenotype", "Starting from a genome-wide expression profiling, we demonstrate for the first time a functional link between oxygen deprivation and the modulation of long noncoding transcripts from ultraconserved regions, termed transcribed-ultraconserved regions (T-UCRs)" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/24037088", "http://www.ncbi.nlm.nih.gov/pubmed/21298224", "http://www.ncbi.nlm.nih.gov/pubmed/22617881", "http://www.ncbi.nlm.nih.gov/pubmed/22328099", "http://www.ncbi.nlm.nih.gov/pubmed/24247010", "http://www.ncbi.nlm.nih.gov/pubmed/18323801", "http://www.ncbi.nlm.nih.gov/pubmed/20802525", "http://www.ncbi.nlm.nih.gov/pubmed/20383195" ]

[]

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

[ "Palbociclib is useful for women with hormone receptor-positive, human epidermal growth factor receptor 2-negative breast cancer." ]

[ "hormone receptor-positive, human epidermal growth factor receptor 2-negative" ]

[ "Women with hormone receptor-positive, human epidermal growth factor receptor 2- negative breast cancer-the most common subtype-have new options as palbociclib and similar drugs debut. ", "We aimed to assess the safety and efficacy of palbociclib in combination with letrozole as first-line treatment of patients with advanced, oestrogen receptor-positive, HER2-negative breast cancer." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/25524798", "http://www.ncbi.nlm.nih.gov/pubmed/25792301", "http://www.ncbi.nlm.nih.gov/pubmed/26236140" ]

[]

[ "http://www.disease-ontology.org/api/metadata/DOID:1612", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001943" ]

[ "Congenital deafness is one of the characteristics of Pendred syndrome patients." ]

[ "yes" ]

[ "Pendred Syndrome can be characterized by the triad composed of familial goitre, abnormal perchlorate discharge and congenital deafness.", "Pendred syndrome is an autosomal recessive disorder characterized by congenital deafness and goiter. ", "Pendred syndrome comprises congenital sensorineural hearing loss, thyroid goiter, and positive perchlorate discharge test. ", "The cause of the congenital deafness in Pendred syndrome is obscure, although a Mondini type malformation of the cochlea exists in some patients.", "Pendred syndrome is an autosomal recessive disorder characterized by congenital deafness and goiter.", "Pendred syndrome is the autosomal recessively transmitted association of familial goiter and congenital deafness.", "Pendred syndrome (PDS) is an autosomal recessive disorder characterized by congenital deafness, goiter and iodide organification defect.", "Pendred syndrome is a recessively inherited disorder with the hallmark features of congenital deafness and thyroid goitre.", "Pendred syndrome, a common autosomal-recessive disorder characterized by congenital deafness and goiter, is caused by mutations of SLC26A4, which codes for pendrin.", "These studies provide compelling evidence that defects in pendrin cause Pendred syndrome thereby launching a new area of investigation into thyroid physiology, the pathogenesis of congenital deafness and the role of altered sulphate transport in human disease.", "Mutations in the Pendred syndrome gene have been observed in patients with deafness and vestibular aqueduct dilatation, in the absence of other Pendred syndrome features.", "The occurrence of congenital deafness, mutism and goitre unassociated with cretinism or mental retardation in euthyroid patients is known as Pendred's Syndrome.", "The autosomal recessive Pendred's syndrome is defined by congenital sensorineural deafness, goiter, and impaired iodide organification.", "Pendred's syndrome is an autosomal recessive disease characterized by goiter, impaired iodide organification, and congenital sensorineural deafness.", "Pendred syndrome is an autosomal recessive disorder characterized by congenital sensorineural deafness, goiter, and impaired iodide organification.", "Pendred's syndrome is manifested by congenital sensorineural deafness in association with familial goiter due to defective organic binding of iodine in the thyroid gland.", "Although the textbook view of the Pendred syndrome is that of an autosomal recessive condition characterised by deafness and goitre, it is increasingly clear that not all patients present this classical clinical description.", "Pendred's syndrome may account for up to 10% of the cases with hereditary hearing loss, and pendrin mutations have also been found in a kindred with non-syndromic deafness.", "Pendred syndrome comprises the association of severe congenital sensorineural deafness with thyroid pathology.", "The first one is named Pendred Syndrome (PS) when deafness is associated with thyroid goiter; the second is called DFNB4, when no other symptoms are present.", "Pendred syndrome is an autosomal recessive disorder characterized by sensorineural deafness, a partial defect in iodide organification, and dyshormonogenetic goiter.", "Pendred syndrome and non-syndromic recessive deafness associated with enlarged vestibular aqueduct (NSRD with EVA) are caused by mutations in the SLC26A4 (PDS) gene.", "Although the textbook view of Pendred syndrome is that of an autosomal recessive condition characterized by deafness and goitre, it is increasingly clear that not all such patients present this classical clinical picture. ", "The occurrence of congenital deafness, mutism and goitre unassociated with cretinism or mental retardation in euthyroid patients is known as Pendred's Syndrome. ", "The cause of the congenital deafness in Pendred syndrome is obscure, although a Mondini type malformation of the cochlea exists in some patients. ", "The discovery of mutations in the SLC26A4 gene in patients with Pendred syndrome (congenital deafness, goiter, and defective iodide organification) suggested a possible role for the encoded protein, pendrin, as an apical iodide transporter. ", "Pendred syndrome is a recessively inherited disorder with the hallmark features of congenital deafness and thyroid goitre. ", "Pendred&apos;s syndrome is manifested by congenital sensorineural deafness in association with familial goiter due to defective organic binding of iodine in the thyroid gland. The majority of patients with Pendred&apos;s syndrome are euthyroid. We report on an unusual case of a patient with Pendred&apos;s syndrome presenting with amenorrhea and late-onset hypothyroidism.", " Although the textbook view of Pendred syndrome is that of an autosomal recessive condition characterized by deafness and goitre, it is increasingly clear that not all such patients present this classical clinical picture. Malformations of the inner ear, specifically enlargement of the vestibular aqueduct, are common in Pendred syndrome and mutations in the PDS (Pendred Syndrome) gene have been recorded in patients presenting with deafness and vestibular aqueduct dilatation only, without other features of Pendred syndrome.", "The occurrence of congenital deafness, mutism and goitre unassociated with cretinism or mental retardation in euthyroid patients is known as Pendred&apos;s Syndrome. It has been estimated that 4-10 % of children with congenital deafness suffer from this condition.", "Malformations of the inner ear, specifically enlargement of the vestibular aqueduct, are common in Pendred syndrome and mutations in the PDS (Pendred Syndrome) gene have been recorded in patients presenting with deafness and vestibular aqueduct dilatation only, without other features of Pendred syndrome. Since this is the most common radiological malformation of the cochlea in deaf patients, we investigated what proportion of such cases were due to mutation of the PDS gene.", "Although the textbook view of Pendred syndrome is that of an autosomal recessive condition characterized by deafness and goitre, it is increasingly clear that not all such patients present this classical clinical picture. Malformations of the inner ear, specifically enlargement of the vestibular aqueduct, are common in Pendred syndrome and mutations in the PDS (Pendred Syndrome) gene have been recorded in patients presenting with deafness and vestibular aqueduct dilatation only, without other features of Pendred syndrome." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/15320950", "http://www.ncbi.nlm.nih.gov/pubmed/9070918", "http://www.ncbi.nlm.nih.gov/pubmed/10502702", "http://www.ncbi.nlm.nih.gov/pubmed/1810081", "http://www.ncbi.nlm.nih.gov/pubmed/10602116", "http://www.ncbi.nlm.nih.gov/pubmed/9398842", "http://www.ncbi.nlm.nih.gov/pubmed/21551164", "http://www.ncbi.nlm.nih.gov/pubmed/22717225", "http://www.ncbi.nlm.nih.gov/pubmed/8979104", "http://www.ncbi.nlm.nih.gov/pubmed/10443670", "http://www.ncbi.nlm.nih.gov/pubmed/9585042", "http://www.ncbi.nlm.nih.gov/pubmed/11375792", "http://www.ncbi.nlm.nih.gov/pubmed/21704276", "http://www.ncbi.nlm.nih.gov/pubmed/21274344", "http://www.ncbi.nlm.nih.gov/pubmed/18250610", "http://www.ncbi.nlm.nih.gov/pubmed/16924389", "http://www.ncbi.nlm.nih.gov/pubmed/22109890", "http://www.ncbi.nlm.nih.gov/pubmed/16482981", "http://www.ncbi.nlm.nih.gov/pubmed/10037079", "http://www.ncbi.nlm.nih.gov/pubmed/11716048", "http://www.ncbi.nlm.nih.gov/pubmed/8706311", "http://www.ncbi.nlm.nih.gov/pubmed/9920104", "http://www.ncbi.nlm.nih.gov/pubmed/8630498", "http://www.ncbi.nlm.nih.gov/pubmed/19318451", "http://www.ncbi.nlm.nih.gov/pubmed/10700480", "http://www.ncbi.nlm.nih.gov/pubmed/8476169", "http://www.ncbi.nlm.nih.gov/pubmed/14727345", "http://www.ncbi.nlm.nih.gov/pubmed/23459462", "http://www.ncbi.nlm.nih.gov/pubmed/17299139" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D003638" ]

[ "SGLT2 inhibitors can be associated with urogenital infections related to the enhanced glycosuria, and low blood pressure." ]

[ "urinary tract infections", "genital infections", "low blood pressure" ]

[ "Due to side effects such as urinary tract and genital infections and decrease in blood pressure, proper patient selection for drug initiation and close monitoring will be important. ", "Urogenital side-effects related to the enhanced glycosuria can be troublesome, yet seldom lead to discontinuation.", "Promotion of urinary loss of glucose by SGLT2 inhibitors embodies a new principle of control in type 2 diabetes that has several advantages with some urogenital side-effects, both of which are evaluated in this review. ", "Promotion of urinary loss of glucose by SGLT2 inhibitors embodies a new principle of control in type 2 diabetes that has several advantages with some urogenital side-effects, both of which are evaluated in this review", "Effect of SGLT2 inhibitors in a murine model of urinary tract infection with Candida albicans.", "Promotion of urinary loss of glucose by SGLT2 inhibitors embodies a new principle of control in type 2 diabetes that has several advantages with some urogenital side-effects,", "Urogenital side-effects related to the enhanced glycosuria can be troublesome, yet seldom lead to discontinuation.", "Promotion of urinary loss of glucose by SGLT2 inhibitors embodies a new principle of control in type 2 diabetes that has several advantages with some urogenital side-effects, both of which are evaluated in this review.", "There are some side effects that warrant further investigation and establishing whether SGLT2 inhibition provides a renal benefit relies on future long-term studies with specific renal end-points.", "It should be noted that the currently approved agents have side effects that include an increased incidence of genital infections, predominantly in women." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/24341330", "http://www.ncbi.nlm.nih.gov/pubmed/22977310", "http://www.ncbi.nlm.nih.gov/pubmed/24400675", "http://www.ncbi.nlm.nih.gov/pubmed/24825435", "http://www.ncbi.nlm.nih.gov/pubmed/23807940", "http://www.ncbi.nlm.nih.gov/pubmed/24631482", "http://www.ncbi.nlm.nih.gov/pubmed/25488697", "http://www.ncbi.nlm.nih.gov/pubmed/24455799", "http://www.ncbi.nlm.nih.gov/pubmed/23042029", "http://www.ncbi.nlm.nih.gov/pubmed/25962253" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D051297", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D064420", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D065606" ]

[ "Excellent prognosis in a subset of patients with Ewing sarcoma identified at diagnosis by CD56 using flow cytometryIn patients with localized nonpelvic disease, those expressing low/negative CD56 had 100% PFS versus 40% in the high expressing group (P = 0.02)", "CD56 expression could be used to reveal Ewing sarcoma patients with excellent prognosis or patients predisposed to relapse, thus improving treatment stratification and implementation of personalized therapy." ]

[ "yes" ]

[ "Excellent prognosis in a subset of patients with Ewing sarcoma identified at diagnosis by CD56 using flow cytometry", "There was a highly significant correlation between CD56 expression and progression-free survival (PFS; 69% in low/negative expression versus 30% in high expression groups, P = 0.024)", "In patients with localized nonpelvic disease, those expressing low/negative CD56 had 100% PFS versus 40% in the high expressing group (P = 0.02)", "CD56 was found to be an independent prognostic marker with an 11-fold increased risk for relapse in patients with localized disease (P = 0.006)", "CD56 expression could be used to reveal ES patients with excellent prognosis or patients predisposed to relapse, thus improving treatment stratification and implementation of personalized therapy", "Excellent prognosis in a subset of patients with Ewing sarcoma identified at diagnosis by CD56 using flow cytometry.", "Three years after diagnosis the patient presented with severe respiratory difficulty and following resection, the final pathology revealed multiple tumors with foci of high grade sarcoma compatible with primitive neuroectodermal tumor/extraskeletal Ewing sarcoma based on morphology and immunohistochemistry (CD99, CD56).", "CD56 expression could be used to reveal ES patients with excellent prognosis or patients predisposed to relapse, thus improving treatment stratification and implementation of personalized therapy.", "Identification of CD56 and CD57 by flow cytometry in Ewing's sarcoma or primitive neuroectodermal tumor.", "CD56 expression could be used to reveal ES patients with excellent prognosis or patients predisposed to relapse, thus improving treatment stratification and implementation of personalized therapy." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/21467162", "http://www.ncbi.nlm.nih.gov/pubmed/9692823", "http://www.ncbi.nlm.nih.gov/pubmed/22498946" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011379", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012512" ]

[ "Filter Aided Sample Preparation (FASP), a type of proteomic reactor, in which samples dissolved in sodium dodecyl sulfate (SDS) are digested in an ultrafiltration unit." ]

[ "proteomic sample preparation" ]

[ "FASP (filter-aided sample preparation) ", "mouse brain tissue lysate was prepared using filter-aided sample preparation (FASP) method ", " an increased number of confident protein identifications are attained with a filter-aided digestion approach as compared to an in-solution digestion.", "filter-aided sample preparation (FASP)", "In the second step the isolated cells are lysed and processed using 'filter aided sample preparation' (FASP) technique. ", "filter-aided sample preparation (FASP),", "filter assisted sample preparation (FASP) method", "d filter-aided sample preparation (FASP)-", " filter-aided sample preparation (FASP)", "filter-aided sample preparation (FASP)", "Filter Aided Sample Preparation (FASP), a type of proteomic reactor, in which samples dissolved in sodium dodecyl sulfate (SDS) are digested in an ultrafiltration unit.", " filter-aided sample preparation (FASP) protocol ", "by combining a filter-aided sample preparation method a" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/23603217", "http://www.ncbi.nlm.nih.gov/pubmed/22949036", "http://www.ncbi.nlm.nih.gov/pubmed/24051509", "http://www.ncbi.nlm.nih.gov/pubmed/24022122", "http://www.ncbi.nlm.nih.gov/pubmed/24288579", "http://www.ncbi.nlm.nih.gov/pubmed/22324799", "http://www.ncbi.nlm.nih.gov/pubmed/23784971", "http://www.ncbi.nlm.nih.gov/pubmed/24289162", "http://www.ncbi.nlm.nih.gov/pubmed/23126408", "http://www.ncbi.nlm.nih.gov/pubmed/23436586", "http://www.ncbi.nlm.nih.gov/pubmed/24309553", "http://www.ncbi.nlm.nih.gov/pubmed/23214492", "http://www.ncbi.nlm.nih.gov/pubmed/22092713" ]

[]

[]

[ "Reduced dosage of ERF, which encodes an inhibitory ETS transcription factor directly bound by ERK1/2 causes complex craniosynostosis (premature fusion of the cranial sutures) in humans and mice. Features of this newly recognized clinical disorder include multiple-suture synostosis, craniofacial dysmorphism, Chiari malformation and language delay." ]

[]

[ "Reduced dosage of ERF causes complex craniosynostosis in humans and mice and links ERK1/2 signaling to regulation of osteogenesis", "we show that reduced dosage of ERF, which encodes an inhibitory ETS transcription factor directly bound by ERK1/2 (refs. 2,3,4,5,6,7), causes complex craniosynostosis (premature fusion of the cranial sutures) in humans and mice. Features of this newly recognized clinical disorder include multiple-suture synostosis, craniofacial dysmorphism, Chiari malformation and language delay. Mice with functional Erf levels reduced to ∼30% of normal exhibit postnatal multiple-suture synostosis; by contrast, embryonic calvarial development appears mildly delayed" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/23354439" ]

[]

[ "http://www.uniprot.org/uniprot/ERK1_CANAL", "http://www.disease-ontology.org/api/metadata/DOID:2340", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0070371" ]

[ "Chronic kidney disease (CKD), is a progressive loss in renal function over a period of months or years. The symptoms of worsening kidney function are non-specific, and might include feeling generally unwell and experiencing a reduced appetite. Often, chronic kidney disease is diagnosed as a result of screening of people known to be at risk of kidney problems, such as those with high blood pressure or diabetes and those with a blood relative with chronic kidney disease. Chronic kidney disease may also be identified when it leads to one of its recognized complications, such as cardiovascular disease, anemia or pericarditis. It is differentiated from acute kidney disease in that the reduction in kidney function must be present for over 3 months.", "Yes, there is a number of urine biomarkers used for early detection of chronic kidney disease." ]

[ "yes" ]

[ "Kidney and urine proteomic biomarkers are considered as promising diagnostic tools to predict CKD progression early in diabetic nephropathy, facilitating timely and selective intervention that may reduce the related health-care expenditures.", "Both blood and urine biomarkers are reviewed in this paper and offer a considerable opportunity to enhance the understanding of the pathophysiology and known epidemiology of these recently defined syndromes.", "Cardiorenal syndromes (CRS) have been subclassified as five defined entities which represent clinical circumstances in which both the heart and the kidney are involved in a bidirectional injury and dysfunction via a final common pathway of cell-to-cell death and accelerated apoptosis mediated by oxidative stress.", "There is a strong association between both acute and chronic dysfunction of the heart and kidneys with respect to morbidity and mortality.", "Both blood and urine biomarkers, including the assessment of catalytic iron, a critical element to the generation of oxygen-free radicals and oxidative stress, are reviewed in this paper.", "Identification of urine biomarkers has proven to be beneficial in recent years because of ease of handling, stability, and the ability to standardize the various markers to creatinine or other peptides generally already present in the urine. Recent markers such as neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), and podocin have garnered a lot of attention. The emergence of these and other biomarkers is largely because of the evolution of novel genomic and proteomic applications in investigations of acute kidney injury and chronic kidney disease." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/20425065", "http://www.ncbi.nlm.nih.gov/pubmed/24315007", "http://www.ncbi.nlm.nih.gov/pubmed/24281781", "http://www.ncbi.nlm.nih.gov/pubmed/23758910", "http://www.ncbi.nlm.nih.gov/pubmed/24308223", "http://www.ncbi.nlm.nih.gov/pubmed/24065527", "http://www.ncbi.nlm.nih.gov/pubmed/23344473", "http://www.ncbi.nlm.nih.gov/pubmed/21151537", "http://www.ncbi.nlm.nih.gov/pubmed/23339563", "http://www.ncbi.nlm.nih.gov/pubmed/24133923", "http://www.ncbi.nlm.nih.gov/pubmed/21286212", "http://www.ncbi.nlm.nih.gov/pubmed/24224012", "http://www.ncbi.nlm.nih.gov/pubmed/24205707", "http://www.ncbi.nlm.nih.gov/pubmed/23617441", "http://www.ncbi.nlm.nih.gov/pubmed/22189039", "http://www.ncbi.nlm.nih.gov/pubmed/21538916", "http://www.ncbi.nlm.nih.gov/pubmed/23061738", "http://www.ncbi.nlm.nih.gov/pubmed/22914685", "http://www.ncbi.nlm.nih.gov/pubmed/21816077", "http://www.ncbi.nlm.nih.gov/pubmed/24152229" ]

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[ "Accelerometer assessment measuring overall physical activity (PAL), constant strain postures (CSP), standing time (ST) and lying time (LT)...\nThe following parameters of physical activity were recorded: time upright (standing or walking), time standing, time walking, and step count." ]

[ "Physical activity", "PA", "PAL", "Constant Strain Postures", "CSP", "constant postures", "Standing time", "ST", "Lying time", "LT" ]

[ "accelerometer assessment measuring overall physical activity (PAL), constant strain postures (CSP), standing time (ST) and lying time (LT)", "Physical activity was measured for 7 days at both baseline and at 3 months with an RT3 accelerometer", "wearing an accelerometer to assess physical activity in daily life", "An accelerometer was used to objectively assess their activity level ", "objective activity data to determine whether patients with chronic lower back pain report their activity levels as accurately as controls do. DESIGN: A cross-sectional study was performed in patients and controls. SETTING: The study was carried out in the daily environment of the subjects. SUBJECTS: Thirty-two chronic lower back pain patients with symptoms more than three months and 20 healthy controls from the Netherlands, aged 18-65 years. MAIN MEASURES: A tri-axial accelerometer was worn for five weekdays", "During 14days physical activity in daily life was measured, with both an electronic diary and an accelerometer", "physical activity in daily life was measured with an accelerometer", "physical activity (PA) in individuals with chronic low back pain (CLBP). Thirty-eight participants with non-specific CLBP (29=distressed; 9=non-distressed) were recruited. PA levels were measured using an accelerometer (activPAL activity monitor) over a one week period. The following parameters of physical activity were recorded: time upright (standing or walking), time standing, time walking, and step count.", "Physical activity levels will be measured by self report, RT3 triaxial accelerometer,", "to study the time spent in different static trunk postures which was recorded by a biaxial accelerometer attached to the T12 level", "Daily activities were assessed by measuring body movement with a tri-axial accelerometer", "nighttime activity data from 18 patients diagnosed with chronic back pain. The patients were followed for 6 days and 5 nights. Pain levels were collected every 90 min between 0800 hours and 2,200 hours using a computerized electronic diary. Activity levels were collected using a wrist accelerometer (Actiwatch AW-64). The Actiwatch sampled activity counts every 1 min. Patients were asked to wear the Actiwatch on their non-dominant arm.", " 8-h accelerometer assessment in their daily life (physical activity level (PAL), number of constant postures (CP)", "The activity levels were collected automatically using a wrist accelerometer and were sampled every minute.", "Physical activity in daily life, expressed as whole-body acceleration measured with a triaxial accelerometer (Tracmor)," ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/23865908", "http://www.ncbi.nlm.nih.gov/pubmed/18752975", "http://www.ncbi.nlm.nih.gov/pubmed/19945891", "http://www.ncbi.nlm.nih.gov/pubmed/16437292", "http://www.ncbi.nlm.nih.gov/pubmed/15271728", "http://www.ncbi.nlm.nih.gov/pubmed/21872993", "http://www.ncbi.nlm.nih.gov/pubmed/21195646", "http://www.ncbi.nlm.nih.gov/pubmed/23560880", "http://www.ncbi.nlm.nih.gov/pubmed/19895697", "http://www.ncbi.nlm.nih.gov/pubmed/16426878", "http://www.ncbi.nlm.nih.gov/pubmed/20921030", "http://www.ncbi.nlm.nih.gov/pubmed/11387574", "http://www.ncbi.nlm.nih.gov/pubmed/19402888", "http://www.ncbi.nlm.nih.gov/pubmed/20457489", "http://www.ncbi.nlm.nih.gov/pubmed/19945334" ]

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These devices typically consist of a sensor and transducer, an amplifier, and extension cables for connection to an electronic measuring unit. They work on the principle of seismic mass: this mass is restrained by a spring, and when the transducer case is accelerated, the mass moves relative to the case and exerts a force on the spring. The acceleration is calculated by measuring mass displacement or the mass' force on the spring, converted to an electrical signal. Acceleration transducers are available using strain gauges (e.g., metallic foil, piezoresistive), capacitive elements, and piezoelectric elements. Clinical accelerometers are intended for several purposes, including measuring the acceleration of body parts to assess a patient's mobility and/or activity (alone or as a component of activity monitors and gait analyzers respectively); assess tremor (e.g., in patients with Parkinson's disease); and activate pacemakers according" } ]

[ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013001", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D059787", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001416", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D010146", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D059352", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D019567", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D059350", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D017116", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D018710" ]

[ "JASPAR, JASPAR CORE, JASPAR FAM, JASPAR phyloFACTS, JASPAR 2008 update, JASPAR 2010, JASPAR 2014." ]

[ "JASPAR", "JASPAR CORE", "JASPAR FAM", "JASPAR phyloFACTS", "JASPAR 2008 update", "JASPAR 2010", "JASPAR 2014" ]

[ "JASPAR is an open-access database of annotated, high-quality, matrix-based transcription factor binding site profiles for multicellular eukaryotes. The profiles were derived exclusively from sets of nucleotide sequences experimentally demonstrated to bind transcription factors. The database is complemented by a web interface for browsing, searching and subset selection, an online sequence analysis utility and a suite of programming tools for genome-wide and comparative genomic analysis of regulatory regions.", "JASPAR is the most complete open-access collection of transcription factor binding site (TFBS) matrices. In this new release, JASPAR grows into a meta-database of collections of TFBS models derived by diverse approaches. We present JASPAR CORE--an expanded version of the original, non-redundant collection of annotated, high-quality matrix-based transcription factor binding profiles, JASPAR FAM--a collection of familial TFBS models and JASPAR phyloFACTS--a set of matrices computationally derived from statistically overrepresented, evolutionarily conserved regulatory region motifs from mammalian genomes. JASPAR phyloFACTS serves as a non-redundant extension to JASPAR CORE, enhancing the overall breadth of JASPAR for promoter sequence analysis", "JASPAR 2010: the greatly expanded open-access database of transcription factor binding profiles.", "JASPAR 2014: an extensively expanded and updated open-access database of transcription factor binding profiles.", "The fifth major release greatly expands the heart of JASPAR-the JASPAR CORE subcollection, which contains curated, non-redundant profiles-with 135 new curated profiles (74 in vertebrates, 8 in Drosophila melanogaster, 10 in Caenorhabditis elegans and 43 in Arabidopsis thaliana; a 30% increase in total) and 43 older updated profiles (36 in vertebrates, 3 in D. melanogaster and 4 in A. thaliana; a 9% update in total). The new and updated profiles are mainly derived from published chromatin immunoprecipitation-seq experimental datasets. In addition, the web interface has been enhanced with advanced capabilities in browsing, searching and subsetting. Finally, the new JASPAR release is accompanied by a new BioPython package, a new R tool package and a new R/Bioconductor data package to facilitate access for both manual and automated methods.", "JASPAR, the open access database of transcription factor-binding profiles: new content and tools in the 2008 update.", "In this new release, JASPAR grows into a meta-database of collections of TFBS models derived by diverse approaches. We present JASPAR CORE--an expanded version of the original, non-redundant collection of annotated, high-quality matrix-based transcription factor binding profiles, JASPAR FAM--a collection of familial TFBS models and JASPAR phyloFACTS--a set of matrices computationally derived from statistically overrepresented, evolutionarily conserved regulatory region motifs from mammalian genomes.", "JASPAR phyloFACTS serves as a non-redundant extension to JASPAR CORE, enhancing the overall breadth of JASPAR for promoter sequence analysis. The new release of JASPAR is available at http://jaspar.genereg.net. .", "JASPAR phyloFACTS serves as a non-redundant extension to JASPAR CORE, enhancing the overall breadth of JASPAR for promoter sequence analysis. The new release of JASPAR is available at http://jaspar.", "JASPAR phyloFACTS serves as a non-redundant extension to JASPAR CORE, enhancing the overall breadth of JASPAR for promoter sequence analysis. The new release of JASPAR is available at http://jaspar.genereg.net." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/16381983", "http://www.ncbi.nlm.nih.gov/pubmed/19906716", "http://www.ncbi.nlm.nih.gov/pubmed/24194598", "http://www.ncbi.nlm.nih.gov/pubmed/14681366", "http://www.ncbi.nlm.nih.gov/pubmed/18006571" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D019991" ]

[ "The IFAP syndrome is a rare X-linked genetic disorder characterized by the triad of follicular ichthyosis, atrichia, and photophobia." ]

[ "follicular ichthyosis", "atrichia", "photophobia" ]

[ "The IFAP syndrome is a rare X-linked genetic disorder characterized by the triad of follicular ichthyosis, atrichia, and photophobia.", "Mutations in MBTPS2 have been reported to cause a broad phenotypic spectrum of X-linked genodermatoses, including IFAP (ichthyosis follicularis; atrichia and photophobia) syndrome (OMIM 308205) with or without BRESHECK (brain anomalies, retardation of mentality and growth, ectodermal dysplasia, skeletal malformations, Hirschsprung disease, ear deformity and deafness, eye hypoplasia, cleft palate, cryptorchidism, and kidney dysplasia/hypoplasia) syndrome, keratosis follicularis spinulosa decalvans (KFSD; OMIM 308800) and an X-linked form of Olmsted syndrome. We report a recurrent intronic mutation in MBTPS2 (c.671-9T>G) in a Chinese patient with the typical triad of IFAP syndrome (i.e. ichthyosis, atrichia and photophobia), along with pachyonychia, palmoplantar and periorificial keratoderma, which were reminiscent of Olmsted syndrome. ", "The ichthyosis follicular with atrichia and photophobia syndrome (IFAP) is a rare X-linked multiple congenital malformation syndrome.", "This patient presented with a severe IFAP/BRESHECK phenotype including ichthyosis follicular, atrichia, photophobia, brain anomalies, global developmental delay, Hirschsprung disease and kidney hypoplasia. ", "The clinical findings include all the features that dermotrichic and ichthyosis follicularis-alopecia-photophobia (IFAP) syndrome have in common and in addition those that characterize IFAP syndrome (photophobia, recurrent respiratory infections, etc.", "Photoletter to the editor: A new variant of ichthyosis follicularis with alopecia and photophobia (IFAP) syndrome with coexisting psoriasiform lesions and palmoplantar keratoderma. IFAP-PPK syndrome?", "Ichthyosis follicularis, atrichia, and photophobia (IFAP) are typical features of a rare neuroichthyosis termed IFAP syndrome.", "Child with manifestations of dermotrichic syndrome and ichthyosis follicularis-alopecia-photophobia (IFAP) syndrome.", "These features correspond to the ichthyosis follicularis, alopecia, photophobia (IFAP) syndrome.", "Ichthyosis follicularis, atrichia, and photophobia (IFAP) syndrome is a rare congenital disorder.", "Ichthyosis follicularis with atrichia and photophobia (IFAP) syndrome in two unrelated female patients.", "Linear lesions reflecting lyonization in women heterozygous for IFAP syndrome (ichthyosis follicularis with atrichia and photophobia).", "Ichthyosis follicularis, alopecia, and photophobia (IFAP) syndrome due to mutation of the gene MBTPS2 in a large Australian kindred.", "Ichthyosis follicularis, alopecia and photophobia (IFAP) syndrome treated with acitretin.", "Atrichia, ichthyosis, follicular hyperkeratosis, chronic candidiasis, keratitis, seizures, mental retardation and inguinal hernia: a severe manifestation of IFAP syndrome?", "Ocular findings in ichthyosis follicularis-alopecia-photophobia (IFAP) syndrome.", "We describe an 18-month-old male infant suffering from the ichthyosis follicularis, atrichia, and photophobia (IFAP) syndrome and further delineate the clinical phenotype.", "The clinical findings include all the features that dermotrichic and ichthyosis follicularis-alopecia-photophobia (IFAP) syndrome have in common and in addition those that characterize IFAP syndrome (photophobia, recurrent respiratory infections, etc.), those that are present only in dermotrichic syndrome (nail anomalies, hypohydrosis, megacolon, vertebral defects, etc.) and additional ones (enamel dysplasia, renal anomalies, inguinal hernia, etc.).", "The clinical findings include all the features that dermotrichic and ichthyosis follicularis-alopecia-photophobia (IFAP) syndrome have in common and in addition those that characterize IFAP syndrome (photophobia,", "Ichthyosis follicularis, atrichia, and photophobia (IFAP) are typical features of a rare neuroichthyosis termed IFAP syndrome.", "These features correspond to the ichthyosis follicularis, alopecia, photophobia (IFAP) syndrome.", "Ichthyosis follicularis, atrichia, and photophobia (IFAP) syndrome is a rare congenital disorder.", "The ichthyosis follicular with atrichia and photophobia syndrome (IFAP) is a rare X-linked multiple congenital malformation syndrome." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/10398262", "http://www.ncbi.nlm.nih.gov/pubmed/1915513", "http://www.ncbi.nlm.nih.gov/pubmed/19689518", "http://www.ncbi.nlm.nih.gov/pubmed/21886760", "http://www.ncbi.nlm.nih.gov/pubmed/14708109", "http://www.ncbi.nlm.nih.gov/pubmed/24090718", "http://www.ncbi.nlm.nih.gov/pubmed/15370546", "http://www.ncbi.nlm.nih.gov/pubmed/25685152", "http://www.ncbi.nlm.nih.gov/pubmed/21315478", "http://www.ncbi.nlm.nih.gov/pubmed/16268889", "http://www.ncbi.nlm.nih.gov/pubmed/10694306", "http://www.ncbi.nlm.nih.gov/pubmed/12004300", "http://www.ncbi.nlm.nih.gov/pubmed/1456297", "http://www.ncbi.nlm.nih.gov/pubmed/10326971", "http://www.ncbi.nlm.nih.gov/pubmed/24313295" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013577", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012816", "http://www.disease-ontology.org/api/metadata/DOID:225" ]

[ "The prodrug clopidogrel requires activation by cytochrome P-450 (CYP) enzymes for its antiplatelet effect. Variability in clopidogrel response might be influenced by polymorphisms in genes coding for drug metabolism enzymes (cytochrome P450 CYP2C19), transport proteins (P-glycoprotein) and/or target proteins for the drug (adenosine diphosphate-receptor P2Y12). The CYP2C19 loss-of-function alleles had a gene dose effect on the pharmacodynamics and composite ischemic events of clopidogrel in our study population. Neither the ABCB1 nor the PON1 genotype significantly influenced the antiplatelet effect and clinical outcomes of clopidogrel in these patients" ]

[ "cytochrome P450, CYPC19" ]

[ "The CYP2C19 G681A single polymorphism has been proven to affect clopidogrel responsiveness. ", "This study investigated the effect of coexisting polymorphisms of CYP2C19 and P2Y12 on clopidogrel responsiveness and adverse clinical events in Chinese patient", "ssociation of a functional polymorphism in the clopidogrel target receptor gene, P2Y12", "We tested for an association of gene sequence variations in P2Y12 and occurrence of neurological adverse events in patients with symptomatic peripheral artery disease (PAD) during clopidogrel treatment", "Variability in clopidogrel response might be influenced by polymorphisms in genes coding for drug metabolism enzymes (cytochrome P450 [CYP] family), transport proteins (P-glycoprotein) and/or target proteins for the drug (adenosine diphosphate-receptor P2Y12)", "Polymerase chain reaction-based genotyping evaluated polymorphisms in the CYP2C19, CYP2C9, CYP3A4, CYP3A5, ABCB1, P2Y12, and CES genes. ", "The prodrug clopidogrel requires activation by cytochrome P-450 (CYP) enzymes for its antiplatelet effect", "Carriers of the CYP2C19*2 and *4 alleles showed reduced platelet inhibition after a clopidogrel 600-mg loading dose but responded to higher loading and maintenance dose regimens", "Carriers of the CYP2C19*17 T-allele, with increased clopidogrel activation, had a 37% relative reduction in the TLR incidence, the primary end point", "The cytochrome P450 (CYP) 2C19*2 polymorphism is associated with reduced responsiveness to clopidogrel and poor clinical outcome after stent implantation", "From these results it is suggested that CYP2C19*2 polymorphism is associated with subclinical thrombus formation among Japanese patients receiving clopidogrel. ", "To determine the effect of various SNPs on post-clopidogrel platelet reactivity and clinical outcome. MATERIALS & METHODS: Cytochrome 2C19 (CYP2C19) loss-of-function (LOF; *2, *3) and gain-of-function (GOF; *17) allelic variants, together with ABCB1 (3435 C→T and 2677 G→T/A) and paraoxonase-1 (PON-1; 192 Q→R) SNPs were analyzed in 189 patients after elective stent implantation who participated in a randomized, placebo-controlled trial (NCT00638326)", "Chinese people are more frequent carriers of cytochrome P450 2C19 (CYP2C19) loss-of-function alleles than Caucasians.", "The aim of this study was to investigate the effect of the CYP2C19, ABCB1, and PON1 variants on clopidogrel pharmacodynamics and clinical outcomes in these patients", "The risk of a low response to clopidogrel and composite ischemic events increased with the number of CYP2C19 loss-of-function alleles.", "However, there were not significant differences in clopidogrel pharmacodynamics and clinical outcomes across the ABCB1 and PON1 genotype groups; bleeding was not significantly different across the CYP2C19, ABCB1, and PON1 genotype groups", "The CYP2C19 loss-of-function alleles had a gene dose effect on the pharmacodynamics and composite ischemic events of clopidogrel in our study population. Neither the ABCB1 nor the PON1 genotype significantly influenced the antiplatelet effect and clinical outcomes of clopidogrel in these patients" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/23150151", "http://www.ncbi.nlm.nih.gov/pubmed/21806387", "http://www.ncbi.nlm.nih.gov/pubmed/15933261", "http://www.ncbi.nlm.nih.gov/pubmed/21099121", "http://www.ncbi.nlm.nih.gov/pubmed/19463375", "http://www.ncbi.nlm.nih.gov/pubmed/20826260", "http://www.ncbi.nlm.nih.gov/pubmed/23506580" ]

[]

[ "http://www.biosemantics.org/jochem#4275944", "http://www.biosemantics.org/jochem#4260620", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011110", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005796" ]

[ "Yes, valproic acid prolong survival of glioblastoma patients. Valproic acid is an antiepileptic agent with histone deacetylase inhibitor activity shown to sensitize glioblastoma cells to radiation in preclinical models." ]

[ "yes" ]

[ "A Phase 2 Study of Concurrent Radiation Therapy, Temozolomide, and the Histone Deacetylase Inhibitor Valproic Acid for Patients With Glioblastoma.", "PURPOSE: Valproic acid (VPA) is an antiepileptic agent with histone deacetylase inhibitor (HDACi) activity shown to sensitize glioblastoma (GBM) cells to radiation in preclinical models.", " Median overall survival (OS) was 29.6 months (range: 21-63.8 months), and median progression-free survival (PFS) was 10.5 months (range: 6.8-51.2 months). OS at 6, 12, and 24 months was 97%, 86%, and 56%, respectively. PFS at 6, 12, and 24 months was 70%, 43%, and 38% respectively. ", "CONCLUSIONS: Addition of VPA to concurrent RT/TMZ in patients with newly diagnosed GBM was well tolerated. Additionally, VPA may result in improved outcomes compared to historical data and merits further study.", "Treatment of GDSCs with histone deacetylase inhibitors, TSA and VPA, significantly reduced proliferation rates of the cells and expression of the stem cell markers, indicating differentiation of the cells. Since differentiation into GBM makes them susceptible to the conventional cancer treatments, we posit that use of histone deacetylase inhibitors may increase efficacy of the conventional cancer treatments for eliminating GDSCs.", "Several clinical studies have reported that valproic acid could prolong survival of GBM patients. ", "Our meta-analysis confirmed the benefit of using VPA (HR, 0.56; 95% CI, 0.44-0.71). Sub-group analysis shows that patients treated with VPA had a hazard ratio of 0.74 with a 95% confidence interval of 0.59-0.94 vs. patients treated by other-AEDs and a hazard ratio of 0.66 with a 95% confidence interval of 0.52-0.84 vs. patients treated by administration of non-AEDs. ", ".CONCLUSION: The results of our study suggest that glioblastoma patients may experience prolonged survival due to VPA administration. ", "A new and exciting insight is the potential contribution of VPA to prolonged survival, particularly in glioblastomas. ", "Valproic acid (VPA) is an antiepileptic agent with histone deacetylase inhibitor (HDACi) activity shown to sensitize glioblastoma (GBM) cells to radiation in preclinical models", "Valproic acid use during radiation therapy for glioblastoma associated with improved survival", "Valproic acid (VA) is an antiepileptic drug (AED) and histone deacetylase (HDAC) inhibitor taken by patients with glioblastoma (GB) to manage seizures, and it can modulate the biologic effects of radiation therapy (RT)", "Valproic acid use during radiation therapy for glioblastoma associated with improved survival.", "Prolonged survival with valproic acid use in the EORTC/NCIC temozolomide trial for glioblastoma.", "PURPOSE: Valproic acid (VA) is an antiepileptic drug (AED) and histone deacetylase (HDAC) inhibitor taken by patients with glioblastoma (GB) to manage seizures, and it can modulate the biologic effects of radiation therapy (RT). We investigated whether VA use during RT for GB was associated with overall survival (OS).METHODS AND MATERIALS: Medical records of 544 adults with GB were retrospectively reviewed. Analyses were performed to determine the association of Radiation Therapy Oncology Group recursive partitioning analysis (RTOG RPA) class, seizure history, and concurrent temozolomide (TMZ) and AED use during RT with OS.RESULTS: Seizures before the end of RT were noted in 217 (40%) patients, and 403 (74%) were taking an AED during RT; 29 (7%) were taking VA. ", "When the analysis was restricted to patients who received concurrent TMZ, VA use was marginally associated with OS (P=.057; HR, 0.54; 95% CI, -0.09 to 1.17), independently of RTOG RPA class and seizure history.", "Patients using VPA in combination with temozolomide showed a longer median survival of 69 weeks (95% confidence interval [CI]: 61.7-67.3) compared with 61 weeks (95% CI: 52.5-69.5) in the group without VPA (hazard ratio, 0.63; 95% CI: 0.43-0.92; P = .016), adjusting for age, extent of resection, and O(6)-DNA methylguanine-methyltransferase promoter methylation status.", "Use of VPA together with chemoradiation with temozolomide results in a 2-months' longer survival of patients with GBM." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/26194676", "http://www.ncbi.nlm.nih.gov/pubmed/24874578", "http://www.ncbi.nlm.nih.gov/pubmed/25066904", "http://www.ncbi.nlm.nih.gov/pubmed/21880994", "http://www.ncbi.nlm.nih.gov/pubmed/23680820", "http://www.ncbi.nlm.nih.gov/pubmed/24899645", "http://www.ncbi.nlm.nih.gov/pubmed/23523186" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D014635", "http://www.disease-ontology.org/api/metadata/DOID:3068", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013812", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005909", "http://www.biosemantics.org/jochem#http://www.biosemantics.org/jochem#:4271063", "http://www.biosemantics.org/jochem#4271063" ]

[ "Transcription factor EB (TFEB) is a master regulator of lysosomal biogenesis and autophagy, driving lysosome adaptation to environmental cues, such as starvation, and therefore targeting of TFEB may provide a novel therapeutic strategy for modulating lysosomal function in human disease." ]

[ "Transcription factor EB (TFEB)" ]

[ "In this paper, we identify a novel role for Rags in controlling activation of transcription factor EB (TFEB), a master regulator of autophagic and lysosomal gene expression", "Interaction of TFEB with active Rag heterodimers promoted recruitment of TFEB to lysosomes, leading to mTORC1-dependent phosphorylation and inhibition of TFEB", "Depletion or inactivation of Rags prevented recruitment of TFEB to lysosomes, whereas expression of active Rags induced association of TFEB with lysosomal membranes", "The identification of a master regulator, transcription factor EB (TFEB), that regulates lysosomal biogenesis and autophagy has revealed how the lysosome adapts to environmental cues, such as starvation, and targeting TFEB may provide a novel therapeutic strategy for modulating lysosomal function in human disease", "TFEB regulates lysosomal proteostasis", "Here, we investigate the role of the transcription factor EB (TFEB), a master regulator of lysosomal biogenesis and function, in modulating lysosomal proteostasis in LSDs", "our findings identify TFEB as a specific regulator of lysosomal proteostasis", "the transcription factor EB (TFEB), a master regulator of lysosomal biogenesis and autophagy, is induced by starvation through an autoregulatory feedback loop and exerts a global transcriptional control on lipid catabolism", "A lysosome-to-nucleus signalling mechanism senses and regulates the lysosome via mTOR and TFEB.", "the Transcription Factor EB (TFEB), a master regulator of lysosomal biogenesis, colocalizes with master growth regulator mTOR complex 1 (mTORC1) on the lysosomal membrane", "the lysosome senses its content and regulates its own biogenesis by a lysosome-to-nucleus signalling mechanism that involves TFEB and mTOR", "These data uncover a regulatory network linking an oncogenic transcription factor that is a master regulator of lysosomal biogenesis, TFEB, to mTORC1 and endocytosis.", "We showed that the mouse GRN gene has two possible coordinated lysosomal expression and regulation (CLEAR) sequences that bind to transcription factor EB (TFEB), a master regulator of lysosomal genes.", "In this paper, we identify a novel role for Rags in controlling activation of transcription factor EB (TFEB), a master regulator of autophagic and lysosomal gene expression.", "In particular, active RRAGs interact with the transcription factor EB (TFEB), the master regulator of a gene network that promotes lysosomal biogenesis and autophagy.", "Here, we show that the Transcription Factor EB (TFEB), a master regulator of lysosomal biogenesis, colocalizes with master growth regulator mTOR complex 1 (mTORC1) on the lysosomal membrane.", "Here, we investigate the role of the transcription factor EB (TFEB), a master regulator of lysosomal biogenesis and function, in modulating lysosomal proteostasis in LSDs.", "Here we show that the transcription factor EB (TFEB), a master regulator of lysosomal biogenesis and autophagy, is induced by starvation through an autoregulatory feedback loop and exerts a global transcriptional control on lipid catabolism via Ppargc1α and Ppar1α.", "Transcription factor EB, a master regulator of lysosomal biogenesis, also negatively regulated HIF-1 activity.", "These data uncover a regulatory network linking an oncogenic transcription factor that is a master regulator of lysosomal biogenesis, TFEB, to mTORC1 and endocytosis.", "We found that ceria nanoparticles promote activation of the transcription factor EB, a master regulator of lysosomal function and autophagy, and induce upregulation of genes of the lysosome-autophagy system.", "The transcription factor EB (TFEB), a master gene for lysosomal biogenesis, coordinated this program by driving expression of autophagy and lysosomal genes. ", "In particular, active RRAGs interact with the transcription factor EB (TFEB), the master regulator of a gene network that promotes lysosomal biogenesis and autophagy. ", "We showed that the mouse GRN gene has two possible coordinated lysosomal expression and regulation (CLEAR) sequences that bind to transcription factor EB (TFEB), a master regulator of lysosomal genes. ", "In this paper, we identify a novel role for Rags in controlling activation of transcription factor EB (TFEB), a master regulator of autophagic and lysosomal gene expression. ", "We recently discovered the CLEAR (Coordinated Lysosomal Expression and Regulation) gene network and its master gene transcription factor EB (TFEB), which regulates lysosomal biogenesis and function. ", "Transcription factor EB (TFEB) is the only known transcription factor that is a master regulator of lysosomal biogenesis although its role in macrophages has not been studied. ", "In contrast to its classical function as the waste management machinery, lysosomes are now considered to be an integral part of various cellular signaling processes. The diverse functionality of this single organelle requires a very complex and coordinated regulation of its activity with transcription factor EB (TFEB), a master regulator of lysosomal biogenesis, at its core.", "Here, we show that the Transcription Factor EB (TFEB), a master regulator of lysosomal biogenesis, colocalizes with master growth regulator mTOR complex 1 (mTORC1) on the lysosomal membrane.", "We showed that the mouse GRN gene has two possible coordinated lysosomal expression and regulation (CLEAR) sequences that bind to transcription factor EB (TFEB), a master regulator of lysosomal genes.", "In this paper, we identify a novel role for Rags in controlling activation of transcription factor EB (TFEB), a master regulator of autophagic and lysosomal gene expression.", "We observed that the MiT family of transcription factors, which includes the melanoma oncogene MITF (micropthalmia-associated transcription factor) and the lysosomal master regulator TFEB, had the highest phylogenetic conservation of three consecutive putative GSK3 phosphorylation sites in animal proteomes.", "Transcription factor EB, a master regulator of lysosomal biogenesis, also negatively regulated HIF-1 activity.", "Here, we investigate the role of the transcription factor EB (TFEB), a master regulator of lysosomal biogenesis and function, in modulating lysosomal proteostasis in LSDs.", "Transcription factor EB (TFEB) is the only known transcription factor that is a master regulator of lysosomal biogenesis although its role in macrophages has not been studied.", "These data uncover a regulatory network linking an oncogenic transcription factor that is a master regulator of lysosomal biogenesis, TFEB, to mTORC1 and endocytosis.", "In particular, active RRAGs interact with the transcription factor EB (TFEB), the master regulator of a gene network that promotes lysosomal biogenesis and autophagy." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/22343943", "http://www.ncbi.nlm.nih.gov/pubmed/23457305", "http://www.ncbi.nlm.nih.gov/pubmed/25315655", "http://www.ncbi.nlm.nih.gov/pubmed/23401004", "http://www.ncbi.nlm.nih.gov/pubmed/25750174", "http://www.ncbi.nlm.nih.gov/pubmed/23830905", "http://www.ncbi.nlm.nih.gov/pubmed/25605940", "http://www.ncbi.nlm.nih.gov/pubmed/21804531", "http://www.ncbi.nlm.nih.gov/pubmed/23604321", "http://www.ncbi.nlm.nih.gov/pubmed/23524842", "http://www.ncbi.nlm.nih.gov/pubmed/21617040", "http://www.ncbi.nlm.nih.gov/pubmed/21752829", "http://www.ncbi.nlm.nih.gov/pubmed/23609508", "http://www.ncbi.nlm.nih.gov/pubmed/25060788", "http://www.ncbi.nlm.nih.gov/pubmed/23393155" ]

[]

[]

[ "Under some conditions, both ramoplanin and vancomycin probes produce helicoid staining patterns along the cylindrical walls of B. subtilis cells. This work has implications for the design of ramoplanin derivatives and may influence how other proposed substrate binding antibiotics are studied. This was confirmed by in vitro studies involving a wall-membrane particulate fraction from Gaffkya homari in which peptidoglycan synthesis from UDP-MurNAc-tetrapeptide was inhibited by ramoplanin but not by vancomycin. New results support a two-state model for septal and peripheral PG synthesis at mid-cell, involvement of essential cell division proteins in PG remodeling, and mid-cell localization of proteins that organize PG biosynthesis and that form the protein translocation apparatus.", "Antibiotics which inhibit bacterial peptidoglycan biosynthesis are the most widely used in current clinical practice. Cells treated with ampicillin, D-cycloserine, or fosfomycin had only one chloroplast after cell division, suggesting that the cells divided without chloroplast division. The antibiotics bacitracin and vancomycin showed no obvious effect. Colchicine inhibits Closterium cell elongation after division. Surprisingly, also cinnamycin of Streptomyces cinnamoneus cinnamoneus), previously known to bind specifically to phosphatidylethanolamin of biological membranes, provoked strong cell wall biosynthetic stress. Other substances include fluorescent derivatives of two PG-binding antibiotics, vancomycin and ramoplanin. The muraymycins constitute a new antibiotic family whose core structure contains a glycosylated uronic acid derivative joined by an aminopropane group to a hexahydro-2-imino-4-pyrimidylglycyl residue (epicapreomycidine) containing dipeptide that is further extended by a urea-valine moiety. The muraymycins inhibited peptidoglycan biosynthesis. Ramoplanin is a cyclicdepsipeptide antibiotic that inhibits peptidoglycan biosynthesis. The lantibiotic mersacidin inhibits peptidoglycan biosynthesis at the level of transglycosylation. Ramoplanin, a new lipoglycopeptide antibiotic, inhibits cell wall peptidoglycan biosynthesis in gram-positive bacteria." ]

[ "colchicine", "fosfomycin", "bacitracin", "vancomycin", "D-cycloserine", "seromycin", "ampicillin", "cinnamycin", "ramoplanin", "muraymycin", "mersacidin" ]

[ "Treatment with antibiotics that interfere with peptidoglycan biosynthesis inhibits chloroplast division in the desmid Closterium", "To detect cells just after division, we used colchicine, which inhibits Closterium cell elongation after division", "The antibiotics bacitracin and vancomycin showed no obvious effect.", "cells treated with ampicillin, D-cycloserine, or fosfomycin had only one chloroplast after cell division, suggesting that the cells divided without chloroplast division", "We investigated the effects of antibiotics that interfere with peptidoglycan biosynthesis on chloroplast division in the desmid Closterium peracerosum-strigosum-littorale complex", "Recent advances in pneumococcal peptidoglycan biosynthesis suggest new vaccine and antimicrobial targets.", "Of late, the peptidoglycan (PG) layer, the most important component of the bacterial cell wall has been the subject of drug targeting because, first, it is essential for the survivability of eubacteria and secondly, it is absent in humans.", "Antibiotics which inhibit bacterial peptidoglycan biosynthesis are the most widely used in current clinical practice.", "A dose-response experiment with an E. coli strain susceptible to ampicillin demonstrated a weak effect before the MIC dose.", " In an initial approach, the procedure accurately discriminates susceptible, intermediate and resistant strains of Escherichia coli to amoxicillin/clavulanic acid.", "Surprisingly, also cinnamycin of Streptomyces cinnamoneus cinnamoneus), previously known to bind specifically to phosphatidylethanolamin of biological membranes, provoked strong cell wall biosynthetic stress.", "Here, we compare the staining patterns observed in Bacillus subtilis using fluorescent derivatives of two PG-binding antibiotics, vancomycin and ramoplanin.", "Ramoplanin probes may be better imaging agents than vancomycin probes because they yield clear staining patterns at concentrations well below their minimum inhibitory concentrations.", "Structures of the muraymycins, novel peptidoglycan biosynthesis inhibitors.", "The muraymycins constitute a new antibiotic family whose core structure contains a glycosylated uronic acid derivative joined by an aminopropane group to a hexahydro-2-imino-4-pyrimidylglycyl residue (epicapreomycidine) containing dipeptide that is further extended by a urea-valine moiety.", "The muraymycins inhibited peptidoglycan biosynthesis. ", "Rethinking ramoplanin: the role of substrate binding in inhibition of peptidoglycan biosynthesis.", "Ramoplanin is a cyclicdepsipeptide antibiotic that inhibits peptidoglycan biosynthesis.", "Vancomycin binds to bacterial cell-wall intermediates to achieve its antibiotic effect.", "The lantibiotic mersacidin inhibits peptidoglycan biosynthesis at the level of transglycosylation.", "The lantibiotic mersacidin has been previously reported to interfere with bacterial peptidoglycan biosynthesis", "Here, we focus on the target reaction and describe a mersacidin-induced accumulation of UDP-N-acetylmuramoyl-pentapeptide, indicating that inhibition of peptidoglycan synthesis occurs after the formation of cytoplasmic precursors", "The analogy to the glycopeptides may hint at an interaction of mersacidin with the peptidoglycan precursor rather than with the enzyme. Unlike vancomycin however, mersacidin inhibits peptidoglycan formation from UDP-N-acetylmuramoyl-tripeptide and is active against Enterococcus faecium expressing the vanA resistance gene cluster.", "Inhibition of peptidoglycan biosynthesis in vancomycin-susceptible and -resistant bacteria by a semisynthetic glycopeptide antibiotic.", "LY191145 is a p-chlorobenzyl derivative of LY264826 (A82846B) with activity against both vancomycin-susceptible and -resistant enterococci. Incorporation of L-[14C]lysine into peptidoglycan of intact vancomycin-susceptible and -resistant Enterococcus faecium was inhibited by LY191145 (50% inhibitory concentrations of 1 and 5 microgram/ml, respectively). Inhibition was accompanied by accumulation of UDP-muramyl-peptide precursors in the cytoplasm", "The fact that inhibition of peptidoglycan biosynthesis by LY191145 was not readily antagonized by an excess of free acyl-D-alanyl-D-alanine or acyl-D-alanyl-D-lactate ligands indicates that the manner in which this compound inhibits transglycosylation may not be identical to that of vancomycin.", "Comparison with tunicamycin-treated cells indicated that peptidoglycan rather than teichoic acid metabolism is primarily affected", "Mersacidin caused the excretion of a putative cell wall precursor into the culture supernatant", "Mode of action of the lantibiotic mersacidin: inhibition of peptidoglycan biosynthesis via a novel mechanism?", "Mersacidin is an antibiotic peptide produced by Bacillus sp. strain HIL Y-85,54728 that belongs to the group of lantibiotics. Its activity in vivo against methicillin-resistant Staphylococcus aureus strains compares with that of the glycopeptide antibiotic vancomycin", "Incubation of Staphylococcus simulans 22 with mersacidin resulted in the cessation of growth and slow lysis.", "n contrast to vancomycin, the activity of mersacidin was not antagonized by the tripeptide diacetyl-L-Lys-D-Ala-D-Ala, indicating that on the molecular level its mode of action differs from those of glycopeptide antibiotics.", "Inhibition of peptidoglycan biosynthesis by ramoplanin.", "Ramoplanin, a new lipoglycopeptide antibiotic, inhibits cell wall peptidoglycan biosynthesis in gram-positive bacteria.", "Bacitracin and other antibiotics that inhibit late stages in peptidoglycan biosynthesis induce vancomycin resistance in a high-level, inducibly vancomycin-resistant strain of Enterococcus faecium.", "This effect does not involve a change in the permeability of the cell wall by this drug and is consistent with the identification of D-alanine racemase as a target of D-cycloserine. ", "CONCLUSIONS: Several pathways and genes downregulated by fosfomycin have been identified, in contrast to previously described cell wall active antibiotics, and was explained by starvation response induced by phosphoenolpyruvate accumulation. ", "The target pathway - peptidoglycan biosynthesis - was upregulated following fosfomycin treatment. ", "Ramoplanin, a new lipoglycopeptide antibiotic, inhibits cell wall peptidoglycan biosynthesis in gram-positive bacteria. ", "Fosfomycin inhibited the first enzymatic step of peptidoglycan synthesis, which was followed by decreased levels of peptidoglycan precursors but enhanced levels of substrates such as UDP-GlcNAc and alanine-alanine.", "In contrast, vancomycin and ampicillin inhibited the last stage of peptidoglycan construction on the outer cell surface.", "The target pathway - peptidoglycan biosynthesis - was upregulated following fosfomycin treatment. Modulation of transport processes, cofactor biosynthesis, energy metabolism and nucleic acid biosynthesis was also observed.", "Ramoplanin, a new lipoglycopeptide antibiotic, inhibits cell wall peptidoglycan biosynthesis in gram-positive bacteria." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/9210483", "http://www.ncbi.nlm.nih.gov/pubmed/10801476", "http://www.ncbi.nlm.nih.gov/pubmed/12440876", "http://www.ncbi.nlm.nih.gov/pubmed/21091161", "http://www.ncbi.nlm.nih.gov/pubmed/22280885", "http://www.ncbi.nlm.nih.gov/pubmed/8891144", "http://www.ncbi.nlm.nih.gov/pubmed/21867549", "http://www.ncbi.nlm.nih.gov/pubmed/11751110", "http://www.ncbi.nlm.nih.gov/pubmed/2334153", "http://www.ncbi.nlm.nih.gov/pubmed/7590155", "http://www.ncbi.nlm.nih.gov/pubmed/25224006", "http://www.ncbi.nlm.nih.gov/pubmed/20515462", "http://www.ncbi.nlm.nih.gov/pubmed/7793878", "http://www.ncbi.nlm.nih.gov/pubmed/18558445", "http://www.ncbi.nlm.nih.gov/pubmed/12197711", "http://www.ncbi.nlm.nih.gov/pubmed/22815801", "http://www.ncbi.nlm.nih.gov/pubmed/16832063" ]

[]

[]

[ "Levoxyl monotherapy is associated with increased insomnia compared to a combination of levothyroxine and liothyronine." ]

[ "yes" ]

[ "METHODS: Seventy-one patients diagnosed with primary hypothyroidism were randomly allocated into two study groups: the first group received usual dose of levothyroxine and the second group received combination of levothyroxine and liothyronine for at least 4 months. The main outcomes were psychosocial problems (Goldberg's General Health Questionnaire, GHQ-28), bodyweight, heart rate, blood pressure, and serum lipid levels. RESULTS: In both groups serum thyroid-stimulating hormone levels remained unchanged compared with baseline. Psychosocial scores, body weight, heart rate, blood pressure, and lipid profile in the two groups remained constant. The only exception was a small but significant reduction in anxiety/insomnia in combined treatment group as compared with monotherapy. " ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/19701833" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013974", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D007319" ]

[ "Yes, fatigue is a common complication of glioblastoma patients receiving chemotherapy or radiotherapy." ]

[ "yes" ]

[ "By contrast, fatigue worsened over time, with a difference in mean score of 5.6 points between baseline and 4-month follow-up (P=.02).", "In the GB cohort, the most common side effects were fatigue (56 %), diarrhea (44 %), neutropenia (31 %), and thrombocytopenia (25 %). ", "A total of 37 patients were treated, and treatment was well tolerated: grade 3, 4 nonhematologic toxicity occurred in 30% of patients and consisted mainly of fatigue (14%) and neuropathy (5%); grade 3, 4 hematologic toxicity occurred in 37% of patients and consisted of thrombocytopenia (30%), lymphopenia (4%), and neutropenia (4%). ", "Nonhematologic Grade 3 toxicity was rare, and included fatigue in 4 patients and cognitive disability in 1 patient.", "The most common grade 3 events were neutropenia, thrombocytopenia, fatigue, and infection in 25, 20, 13, and 10%, respectively. ", "Analysis of the results of the VAS Norris scale did not demonstrate an increase in emotional fatigue but did show an increase in physical fatigue that did not reach statistical significance. With regards to the MFI 20 tool, analysis of the results demonstrated a significant increase in general (P=0.0260) as well as physical (P=0.0141) fatigue but there was no difference in the other indices.", "This study demonstrated a progressive increase in physical fatigue in patients with glioblastoma relapse treated with irinotecan-bevacizumab. ", "One patient treated with temozolomide plus isotretinoin plus thalidomide had dose-limiting grade 3 fatigue and rash, and 1 patient receiving all 4 agents had dose-limiting grade 4 neutropenia. ", "The toxicities observed were primarily grade 1 and 2, and the most common were fatigue, hypertension, and headache. ", "Fatigue (41%), rash (62%), and loose stools (58%) constituted the most frequent adverse events, the majority of these being limited to Grade 1/2. ", "The most common grades 3 and 4 nonhematologic toxicities were nausea/vomiting (6.7%) and fatigue (5.8%). ", "Grade 3/4 toxicities included leukopenia (n = 1), lymphopenia (n = 2), thrombocytopenia (n = 1), ALT elevation (n = 3), AST elevation (n = 1), CNS hemorrhage (n = 1), fatigue (n = 1), and thrombotic/embolic events (n = 3); 8 patients required dose reduction. ", "The most common grade 3 or greater adverse events were fatigue (7%), neutropaenia (7%), and thrombocytopaenia (7%).", "Bevacizumab-related toxicity included fatigue (16 patients; 4 grade 3), leukopenia (9; 1 grade 3), anemia (5; 0 grade 3), hypertension (7; 1 grade 3), deep vein thrombosis (4; 1 grade 3) and wound dehiscence (2; 1 grade 3). ", "Tiredness may be caused by the brain injury due to the tumor or the treatment in patients with glioblastoma multiforme (GBM). Some patients describe a sense of tiredness particularly after radiation or oral chemotherapy.", "Levels of tiredness in patients with GBM were greatly affected by the radiotherapy and oral chemotherapy (temozolomide).", "The treatment had no negative effect on HRQOL, however, fatigue (P = 0.02) and constipation (P = 0.01) scales worsened over time.", " This regimen was well tolerated with grade 3/4 toxicities of fatigue, leukopenia, thrombocytopenia and rash requiring dose reductions. ", "The most common atrasentan-related toxicities were grade 1 or 2 rhinitis, fatigue, and edema.", "One patient developed Grade IV fatigue at the 100 ng/mL dose, but the MTD has not been established. ", "Side-effects in all patients have included varying degrees of anorexia, fatigue, ipsilateral forehead dermatitis, blepharitis, and conjunctivitis. ", " Some patients suffered from fatigue and weak concentration about three months after the end of radiotherapy, in some cases even the neurologic state was deteriorated. ", "grade 1-2 common toxicities included fever, chills, fatigue, dizziness, nausea, vomiting and headache, neutrophilia and skin painful reactions appeared regularly at levels 3 and 4 (2.5 mg and 3.5 mg). ", "Ten episodes of grade 3/4 adverse events were observed in nine patients, including fatigue (n = 3), thrombocytopenia (n = 4), and myelotoxicity, febrile neutropenia, and pulmonary embolism (each n = 1).", "Common adverse events were CTCAE grade 1-2 fatigue, loss of appetite, diarrhea, and nausea.", "The most common grade 3-4 toxicities were venous thrombosis, fatigue, skin reactions, encephalopathy, and neuropathy." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/20510539", "http://www.ncbi.nlm.nih.gov/pubmed/19593660", "http://www.ncbi.nlm.nih.gov/pubmed/3008359", "http://www.ncbi.nlm.nih.gov/pubmed/22832897", "http://www.ncbi.nlm.nih.gov/pubmed/20729242", "http://www.ncbi.nlm.nih.gov/pubmed/2168357", "http://www.ncbi.nlm.nih.gov/pubmed/18758912", "http://www.ncbi.nlm.nih.gov/pubmed/22079725", "http://www.ncbi.nlm.nih.gov/pubmed/23419575", "http://www.ncbi.nlm.nih.gov/pubmed/18477765", "http://www.ncbi.nlm.nih.gov/pubmed/23422478", "http://www.ncbi.nlm.nih.gov/pubmed/14649883", "http://www.ncbi.nlm.nih.gov/pubmed/23642624", "http://www.ncbi.nlm.nih.gov/pubmed/18581057", "http://www.ncbi.nlm.nih.gov/pubmed/18990027", "http://www.ncbi.nlm.nih.gov/pubmed/20308655", "http://www.ncbi.nlm.nih.gov/pubmed/23086432", "http://www.ncbi.nlm.nih.gov/pubmed/21514945", "http://www.ncbi.nlm.nih.gov/pubmed/20200024", "http://www.ncbi.nlm.nih.gov/pubmed/21986722", "http://www.ncbi.nlm.nih.gov/pubmed/22090453", "http://www.ncbi.nlm.nih.gov/pubmed/20665891", "http://www.ncbi.nlm.nih.gov/pubmed/19904263", "http://www.ncbi.nlm.nih.gov/pubmed/23184145" ]

[]

[ "http://www.disease-ontology.org/api/metadata/DOID:3073", "http://www.disease-ontology.org/api/metadata/DOID:3068", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005909", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005222", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005221", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D015995" ]

[ "Tay syndrome is a rare autosomal recessive genetic disorder characterized by congenital ichthyosis and trichothiodystrophy (abnormal brittle hair). Other less common features of this syndrome are photosensitivity, low birth weight, short stature, mental retardation, delayed neuromuscular development and other CNS anomalies, dysplasia of nails, hypoplasia of subcutaneous fatty tissue, prematurely aged facial appearance, hypogonadism, cataracts, osteosclerosis, dysphonia, and increased susceptibility to infections." ]

[ "ichthyosis", "trichothiodystrophy" ]

[ "TTD is part of a more broadly defined group of diseases identified as IBIDS (ichthyosis, brittle hair, impaired intelligence, decreased fertility and short stature). Photosensitive cases are also identified as PIBIDS (photosensitivity with IBIDS). Cases without manifest ichthyosis are also identified as PBIDS. These syndromes defy rigorous definition because of clinical variation between patients. The original two cases were described by Tay in oriental siblings, whose parents were first cousins; thus the disease is also known as Tay syndrome. ", "Tay syndrome or IBIDS is a rare autosomal recessive genetic disorder characterized by congenital ichthyosis and abnormal brittle hair (trichothiodystrophy). Other features include photosensitivity, abnormal nails and multiple developmental defects affecting organs mainly derived from neuroectoderm. ", "We report a case of trichothiodystrophy initially classified as Tay syndrome that based on clinical features, complementary exams as well as on the disease evolution was labelled as PIBIDS syndrome.", "Tay-syndrome is a rare monogen-inherited ektodermal dysplastic syndrome with ichtyosis, fragility of the hair and physical and mental retardation. The congenital ichtyosis is ubiquitous. Only the skin on the flexion side of the extremity joints are not involved (orthocerathosis combined with paraceratotic strings).", "In Tay syndrome, the trichothiodystrophy is accompanied by congenital ichthyosis, short stature, delayed physical and mental development and pyramidal tract signs with increase in muscular tone and brisk tendon reflexes. ", "We present a case of Tay syndrome in which a cranial MRI revealed an almost total lack of myelin within the cerebral hemispheres and a patchy hypomyelination of the cerebellum. In accordance, a strongly prolonged visual evoked response pointed to a dysfunction of the white matter in Tay syndrome.", "For example, the brittle hair due to sulphur deficiency (trichothiodystrophy) is nowadays regarded as genetically heterogeneous; three different syndromes can be distinguished: BIDS syndrome, Tay syndrome, and PIBIDS syndrome. ", "The Tay syndrome (congenital ichthyosis with trichothiodystrophy).", "The Tay syndrome is a distinct type of congenital ichthyosis characterized by a peculiar anomaly of hair growth which has been termed trichothiodystrophy. ", "Other features of this syndrome are low birth weight, short stature, mental retardation, delayed neuromuscular development and other CNS anomalies, dysplasia of nails, hypoplasia of subcutaneous fatty tissue, prematurely aged facial appearance, hypogonadism, cataracts, osteosclerosis, dysphonia, and increased susceptibility to infections. " ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/6538137", "http://www.ncbi.nlm.nih.gov/pubmed/18376101", "http://www.ncbi.nlm.nih.gov/pubmed/9050052", "http://www.ncbi.nlm.nih.gov/pubmed/2087835", "http://www.ncbi.nlm.nih.gov/pubmed/20687499", "http://www.ncbi.nlm.nih.gov/pubmed/10797890", "http://www.ncbi.nlm.nih.gov/pubmed/17504703" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D054463", "http://www.disease-ontology.org/api/metadata/DOID:2960" ]

[ "Macrophages, T cells and their respective cytokines play a pivotal role in RA. Rheumatoid arthritis synovial fibroblasts (RASFs) constitute a quite unique cell type that distinguishes RA from other inflammatory conditions of the joints. Activated synovial fibroblasts (SFs) have the ability to invade joint cartilage, actively contributing to joint destruction in RA." ]

[ "Macrophages", "T-cells", "Fibroblast-like synoviocytes (FLS)", "Dendritic cells", "synovial fibroblasts" ]

[ "Integration of GWAS results with cell-type specific gene expression or epigenetic marks have highlighted regulatory T cells and CD4 memory T cells as critical cell types in RA", "A subset of synovial DCs is important in the response to cigarette smoke", " we demonstrate that autoimmune patient (systemic lupus erythematosus and rheumatoid arthritis) serum activates both pDC and B cells, but IRAK1/4 kinase inhibition affects only the pDC response, underscoring the differential IRAK1/4 functional requirements in human immune cell", "In rheumatoid arthritis (RA), activated synovial fibroblasts (SFs) have the ability to invade joint cartilage, actively contributing to joint destruction in RA", "Recently, RASFs have been shown to be able to migrate to non-affected areas and joints through the blood stream and to invade distant cartilage", "MSC interaction with B cells provides stimuli for B-cell survival and therefore may contribute to the pathogenesis of rheumatoid arthritis", "Fibroblast-like synoviocytes (FLS) are resident mesenchymal cells of synovial joints that have been recognized to play an increasingly important role in the pathogenesis of rheumatoid arthritis (RA)", "This study investigates the production of CCL18 in polymorphonuclear neutrophils (PMN), the predominant cell type recruited into synovial fluid (SF)", "In this regard, macrophages, T cells and their respective cytokines play a pivotal role in RA", "it has been understood that resident, fibroblast-like cells contribute significantly to the perpetuation of disease, and that they may even play a role in its initiation", "RASFs are no longer considered passive bystanders but active players in the complex intercellular network of RA", "These rheumatoid arthritis synovial fibroblasts (RASFs) constitute a quite unique cell type that distinguishes RA from other inflammatory conditions of the joints", "The molecular feature that defines the myofibroblast-like phenotype was reflected as an increased proportion of myofibroblast-like cells in the heterogeneous FLS population", "ur findings support the notion that heterogeneity between synovial tissues is reflected in FLS as a stable trait, and provide evidence of a possible link between the behavior of FLS and the inflammation status of RA synovium", "This change was accompanied by a significant decrease in the synovial monocyte/macrophage population", "In RA patients, both etanercept and infliximab are able to induce cell type-specific apoptosis in the monocyte/macrophage population", "Furthermore, fluorescent double-staining showed that the HOXD9 protein was expressed in fibroblast-like synoviocytes (FLS)", "AHR gene expression was demonstrated in rheumatoid synovial tissues and nodules with significantly greater expression in synovia.", "Twenty synovial and eighteen subcutaneous nodule tissue samples from 31 patients with RA were studied. Patient smoking status at the time of tissue collection was established", "Release of the chemokine CCL18 has been widely attributed to antigen-presenting cells, including macrophages and dendritic cells" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/19863844", "http://www.ncbi.nlm.nih.gov/pubmed/15692990", "http://www.ncbi.nlm.nih.gov/pubmed/21160042", "http://www.ncbi.nlm.nih.gov/pubmed/24276088", "http://www.ncbi.nlm.nih.gov/pubmed/18613841", "http://www.ncbi.nlm.nih.gov/pubmed/16567358", "http://www.ncbi.nlm.nih.gov/pubmed/17875202", "http://www.ncbi.nlm.nih.gov/pubmed/12060849", "http://www.ncbi.nlm.nih.gov/pubmed/15641091", "http://www.ncbi.nlm.nih.gov/pubmed/23036591", "http://www.ncbi.nlm.nih.gov/pubmed/20519953" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001172", "http://www.disease-ontology.org/api/metadata/DOID:7148", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0005623" ]

[ "High neuroticism is associated with increased risk to develop Alzheimer's disease. Greater neuroticism is also associated more advanced Alzheimer's disease neuropathology and younger age of dementia onset. Neuroticism's association with late-life dementia mainly reflects vulnerability to stress and anxiety. Neuroticism moderates the relationship between APOE-4 genotype and cognitive outcomes in elderly. Neuroticism also predicts Mild Cognitive Impairment, Aging-Associated Cognitive Decline and cognitive decline among elderly. Alzheimer's disease patients have greater neuroticism relative to controls." ]

[]

[ "RESULTS: Individuals with scores in the top quartile of neuroticism (hazard ratio = 3.1; 95% confidence interval = 1.6-6.0) or the lowest quartile of conscientiousness (hazard ratio = 3.3; 95% confidence interval = 1.4-7.4) had a threefold increased risk of incident AD.", "Five of nine studies found that higher neuroticism was associated with greater dementia risk (pooled hazard ratio [HR] per unit increase on neuroticism score, HR = 1.13, 95% confidence interval [CI] = 1.08-1.18, z = 5.11, p <0.001, N = 3,285), and two studies showed it increased risk of MCI. ", "CONCLUSIONS: Neuroticism increased risk for dementia, and conscientiousness reduced risk. ", "RESULTS: Fully adjusted multivariate analyses showed that the association between the presence of APOE [Latin Small Letter Open E]-4 allele(s) and both outcomes was evident among individuals with high levels of neuroticism and extraversion but not among persons with low levels of these traits. CONCLUSIONS: Phenotypic personality dimensions, primarily neuroticism and extraversion, moderate the relationship between APOE [Latin Small Letter Open E]-4 genotype and cognitive outcomes among older adults.", " Individuals with higher baseline scores on vulnerability to stress, anxiety, and depression (neuroticism: odds ratio, 2.0; 95% confidence interval, 1.2-3.5), or lower scores on order and competence (conscientiousness: odds ratio, 0.4; 95% confidence interval, 0.2-0.9) were less likely to remain asymptomatic in the presence of AD neuropathology. Neuroticism (r = 0.26), low agreeableness (r = -0.34), and some facets were also significantly associated with advanced stages of neurofibrillary tangles, but the associations between personality traits and risk of clinical dementia were mostly unchanged by controlling for the extent of neurofibrillary tangles and Aβ neuritic plaques.", "Using mixed models adjusted for age, sex, education, race, social network size, depression, chronic conditions, disability, neuroticism, extraversion, cognitive activity, and physical activity, more social activity was associated with less cognitive decline during average follow-up of 5.2 years (SD = 2.7).", "RESULTS: After controlling for age, the Alzheimer disease group presented significantly higher scores than normal control subjects on current neuroticism, and significantly lower scores on current extraversion, openness, and conscientiousness, while no significant difference was observed on agreeableness. ", " In analyses of specific cognitive systems, neuroticism subscales were related to decline in episodic memory, working memory, and perceptual speed, but not in semantic memory or visuospatial ability. No component of neuroticism was related to the neuropathologic lesions most commonly associated with late-life dementia. CONCLUSIONS: Neuroticism's association with late-life dementia mainly reflects vulnerability to stress and anxiety and their correlation with decline in the ability to process and retain new information.", "The finding that AD risk is associated with elevated Neuroticism and lower Conscientiousness can be added to the accumulating literature documenting the pathogenic effects of these two traits. ", "tau was also correlated with the psychometric measures of episodic/semantic memory, working memory, and processing speed, and with the personality traits of neuroticism and conscientiousness.", "The pre-morbid personality domain of Neuroticism constituted an interesting and theoretically plausible, yet uninvestigated, candidate for such an association. ", "RESULTS: Midlife Neuroticism predicted younger age of dementia onset in females but not in males.", "Preliminary research suggests that cognitively impaired MS patients exhibit elevation in Neuroticism, and diminution in Extraversion, Agreeableness, and Conscientiousness, as do patients with Alzheimer's disease. ", "On the basis of both self-report and informant report, there was an increase in neuroticism and a decrease in conscientiousness in persons with very mild DAT relative to healthy individuals without it, and in persons with mild DAT relative to those with very mild DAT. ", "CONCLUSIONS: As subjective cognitive complaints in the AACD group were related to neuroticism and gender rather than to cognitive performance, their inclusion in diagnostic concepts such as AACD should be revaluated. ", "Multiple studies of individuals with Alzheimer disease have substantiated significant levels of informant-rated change in several domains and facets of the Neuroticism-Extraversion-Openness Personality Inventory, including increases in Neuroticism and decreases in Extraversion and Conscientiousness relative to premorbid personality traits. ", "RESULTS: The AD patients showed higher neuroticism than the controls with PD (p=0.013). ", "CONCLUSION: Our results support the assumption of specific premorbid characteristics in AD patients, ie increased neuroticism and rigidity.", "Personality change in DAT was consistent with previous reports of increased neuroticism, decreased extraversion, and decreased conscientiousness, with smaller decreases in openness and agreeableness. ", "Neuroticism (r = 0.26), low agreeableness (r = -0.34), and some facets were also significantly associated with advanced stages of neurofibrillary tangles, but the associations between personality traits and risk of clinical dementia were mostly unchanged by controlling for the extent of neurofibrillary tangles and A� neuritic plaques.", "Multiple studies of individuals with Alzheimer disease have substantiated significant levels of informant-rated change in several domains and facets of the Neuroticism-Extraversion-Openness Personality Inventory, including increases in Neuroticism and decreases in Extraversion and Conscientiousness relative to premorbid personality traits", "Multiple studies of individuals with Alzheimer disease have substantiated significant levels of informant-rated change in several domains and facets of the Neuroticism-Extraversion-Openness Personality Inventory, including increases in Neuroticism and decreases in Extraversion and Conscientiousness relative to premorbid personality traits" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/23040035", "http://www.ncbi.nlm.nih.gov/pubmed/19153372", "http://www.ncbi.nlm.nih.gov/pubmed/20973606", "http://www.ncbi.nlm.nih.gov/pubmed/17244848", "http://www.ncbi.nlm.nih.gov/pubmed/18590355", "http://www.ncbi.nlm.nih.gov/pubmed/20438208", "http://www.ncbi.nlm.nih.gov/pubmed/16252381", "http://www.ncbi.nlm.nih.gov/pubmed/7493597", "http://www.ncbi.nlm.nih.gov/pubmed/10718200", "http://www.ncbi.nlm.nih.gov/pubmed/16314587", "http://www.ncbi.nlm.nih.gov/pubmed/16974109", "http://www.ncbi.nlm.nih.gov/pubmed/21835104", "http://www.ncbi.nlm.nih.gov/pubmed/23706517", "http://www.ncbi.nlm.nih.gov/pubmed/23567438", "http://www.ncbi.nlm.nih.gov/pubmed/22040898", "http://www.ncbi.nlm.nih.gov/pubmed/18079420", "http://www.ncbi.nlm.nih.gov/pubmed/10679843", "http://www.ncbi.nlm.nih.gov/pubmed/12767492", "http://www.ncbi.nlm.nih.gov/pubmed/15358438", "http://www.ncbi.nlm.nih.gov/pubmed/23079898", "http://www.ncbi.nlm.nih.gov/pubmed/21905097", "http://www.ncbi.nlm.nih.gov/pubmed/18694539", "http://www.ncbi.nlm.nih.gov/pubmed/21427641", "http://www.ncbi.nlm.nih.gov/pubmed/25274849", "http://www.ncbi.nlm.nih.gov/pubmed/9924832" ]

[]

[]

[ "Everolimus is a drug that binds to mTORC1 and inhibits activation of the mTOR signalling pathway. It is used in targeted cancer therapy protocols or after transplantation for maintenance immunosuppression, against allograft rejection." ]

[]

[ "Target-of-Rapamycin Inhibitors (Sirolimus, Everolimus),", "Although the mTOR inhibitor everolimus is effective for the treatment of patients who have failed TKI therapy, it is important to consider all available treatment options before switching therapy mode of action.", "The mTOR pathway, and its upstream regulators in the PI3K/PTEN/AKT cascade, are altered in a variety of experimental and human malignancies.This has led to the prediction that mTOR inhibitors may be used as anticancer agents. With the recent approval of two mTOR-targeted drugs (temsirolimus and everolimus) for the treatment of renal cell carcinoma and mantle cell lymphoma, this paradigm has been effectively translated into the clinical setting.", "mTOR inhibitors such as Temsirolimus (CCI779) and Everolimus (RAD001) are effective for suppressing cell growth with inhibiting mTOR kinase activity. Rapamycin and its related analogs such as Temsirolimus and Everolimus are less toxic for humans compared with other anti-VEGFR inhibitors and has been used as an immunosuppressive agent. These agents have an inhibitory activity against the mTORC1 complex.", "mTOR inhibitors act on the signaling pathway PI3K/AKT/mTOR, and key molecules are temsirolimus, everolimus, and deforolimus.", "The introduction of the inhibitors of the mammalian target of rapamycin sirolimus and everolimus in renal transplantation has increased the repertoire of immunosuppressive protocols substantially.", "Octreotide and the mTOR inhibitor RAD001 (everolimus) block proliferation and interact with the Akt-mTOR-p70S6K pathway", "RAD001 (everolimus) is a novel agent that is being trialled in the treatment of neuro-endocrine tumours, and is known to interact with mTOR.", "In this cell model, octreotide and RAD001 appear to act through a similar pathway and inhibit the Akt-mTOR-p70S6 kinase pathway downstream of Akt.", "Target of rapamycin inhibitors (sirolimus and everolimus)", "Target of rapamycin inhibitors (TOR-I; sirolimus and everolimus)", "Target of rapamycin inhibitors (TOR-I) (sirolimus, everolimus) are immunosuppressive agents with a novel mode of action", "These three classes are tyrosine kinase inhibitors with sunitinib and sorafenib, the anti-VEGF antibodies (bevacizumab which is associated with alpha interferon in the treatment of advanced kidney cancer) and mTOR inhibitors with temsirolimus and everolimus." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/17890266", "http://www.ncbi.nlm.nih.gov/pubmed/24183081", "http://www.ncbi.nlm.nih.gov/pubmed/19620795", "http://www.ncbi.nlm.nih.gov/pubmed/20384580", "http://www.ncbi.nlm.nih.gov/pubmed/19299048", "http://www.ncbi.nlm.nih.gov/pubmed/16625599", "http://www.ncbi.nlm.nih.gov/pubmed/16699448", "http://www.ncbi.nlm.nih.gov/pubmed/21279702", "http://www.ncbi.nlm.nih.gov/pubmed/18025810", "http://www.ncbi.nlm.nih.gov/pubmed/22139982" ]

[]

[ "http://www.biosemantics.org/jochem#4267185" ]

[ "Yes, mutations in the DNA that affect the splicing pattern of genes have been linked in transcriptome population studies to a number of diseases." ]

[ "yes" ]

[]

[ "http://www.ncbi.nlm.nih.gov/pubmed/21846806", "http://www.ncbi.nlm.nih.gov/pubmed/20707912", "http://www.ncbi.nlm.nih.gov/pubmed/23133393", "http://www.ncbi.nlm.nih.gov/pubmed/21628452", "http://www.ncbi.nlm.nih.gov/pubmed/22784570", "http://www.ncbi.nlm.nih.gov/pubmed/20856809", "http://www.ncbi.nlm.nih.gov/pubmed/18962861", "http://www.ncbi.nlm.nih.gov/pubmed/22723018", "http://www.ncbi.nlm.nih.gov/pubmed/20948966", "http://www.ncbi.nlm.nih.gov/pubmed/19915720" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D056426", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0000395", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0000381", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D040641", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D017398", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D022821", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0000389", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0000398", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0043484", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012326", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D019655", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0045291", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0045292", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0008380", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0006376" ]

[ "Molecular detection of EWS-FLI1 chimeric transcripts in Ewing family tumors is carried out by reverse transcription-polymerase chain reaction (RT-PCR)." ]

[ "Reverse transcription - polymerase chain reaction (RT-PCR)" ]

[ "We evaluated the feasibility and usefulness of reverse transcriptase-polymerase chain reaction (RT-PCR) on fine-needle aspirates for categorization of small blue round cell tumors (SBRCTs). A total of 51 cases, including 25 Ewing sarcoma/peripheral primitive neuroectodermal tumors (PNETs), 11 rhabdomyosarcomas, 13 neuroblastomas, and 2 desmoplastic small round cell tumors (DSRCTs) were analyzed. The detection of the EWS-FLI1 (20/25) and EWS-ERG (4/25) fusion transcripts resolved 24 of 25 cases of Ewing sarcoma/PNET", "Molecular detection of EWS-FLI1 chimeric transcripts in Ewing family tumors by nested reverse transcription-polymerase chain reaction", "To assess the feasibility and reliability of the molecular detection of the transcript originating from the chimeric gene in paraffin-embedded tumor specimens, we performed a nested reverse transcription-polymerase chain reaction (RT-PCR)-based assay to detect the EWS-FLI1 chimeric message in a series of Ewing family tumors. Of 24 paraffin-embedded tumor specimens from 23 cases analyzed, the chimeric message was detectable in 20 (83%) specimens from 20 cases (87%) by this nested RT-PCR assay, whereas none of 7 small round cell tumors not from this family (3 alveolar rhabdomyosarcomas, 2 neuroblastomas, 2 malignant lymphomas) showed detectable chimeric messages", "Using our different sets of exon specific primer pairs, it was possible to detect 4 different breakpoints of ews/fli1 fusion transcripts and the ews/erg fusion by RT-PCR in RNA isolates from formalin-fixed, paraffin-embedded Ewing's tumor tissue.", "Molecular detection of EWS-Fli1 fusion transcripts in formalin-fixed paraffin-embedded material by nested RT-PCR is feasible and is useful for the diagnosis and differential diagnosis of ES/pPNETs.", "We established a novel RT-PCR method, using 3 different exon specific sets of PCR primer pairs, selected according to the coding ews and fli1 nucleotide sequences (NCBI database), suitable for RT-PCR identification of variant ews/fli1 fusion transcripts in RNA isolated from formalin-fixed, paraffin-embedded tissue.", "In this study, we evaluated reverse transcriptase-polymerase chain (RT-PCR) for EWS-FLI1 fusion transcripts in 18 neurally derived small round cell tumours.", "We performed a clinical and pathologic analysis of 112 patients with ES in which EWS-FLI1 fusion transcripts were identified by reverse-transcriptase polymerase chain reaction (RT-PCR).", "Molecular detection of EWS-Fli1 fusion transcripts in formalin-fixed paraffin-embedded material by nested RT-PCR is feasible and is useful for the diagnosis and differential diagnosis of ES/pPNETs.", "RT-PCR confirmed that SK-NEP-1 expresses EWS-FLI1 gene fusion transcripts characteristic of Ewing sarcoma, and DNA sequencing demonstrated the joining of exon 7 of EWS with exon 5 of FLI1 for these transcripts.", "Reverse transcriptase-polymerase chain reaction confirmed the expression of EWS-FLI1 fusion transcripts", "The aims of this study were (1) to present the diverse clinicopathological and molecular profile of EFTs in our settings, (2) to identify a pragmatic approach for diagnosing EFTs, especially for application of ancillary techniques, namely RT-PCR for specific transcripts (EWS-FLI1, EWS-ERG) and FISH for EWSR1 gene rearrangement, in certain cases and (3) to show the utility of tissue microarray in establishing a new FISH test", "[Detection of EWS-FLI1 fusion transcript in Ewing's sarcoma/peripheral primitive neuroectodermal tumors by one-step RT-PCR using paraffin-embedded tissues].", "Molecular detection of EWS-Fli1 fusion transcripts in formalin-fixed paraffin-embedded material by nested RT-PCR is feasible and is useful for the diagnosis and differential diagnosis of ES/pPNETs.", "We established a novel RT-PCR method, using 3 different exon specific sets of PCR primer pairs, selected according to the coding ews and fli1 nucleotide sequences (NCBI database), suitable for RT-PCR identification of variant ews/fli1 fusion transcripts in RNA isolated from formalin-fixed, paraffin-embedded tissue", "Molecular detection of EWS-FLI1 chimeric transcripts in Ewing family tumors by nested reverse transcription-polymerase chain reaction: application to archival paraffin-embedded tumor tissues." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/23475435", "http://www.ncbi.nlm.nih.gov/pubmed/20231617", "http://www.ncbi.nlm.nih.gov/pubmed/9552022", "http://www.ncbi.nlm.nih.gov/pubmed/24293381", "http://www.ncbi.nlm.nih.gov/pubmed/10379685", "http://www.ncbi.nlm.nih.gov/pubmed/17154184", "http://www.ncbi.nlm.nih.gov/pubmed/15363317", "http://www.ncbi.nlm.nih.gov/pubmed/15565546" ]

[]

[]

[ "Recent genome-wide studies mapping the binding sites of CTCF and its interacting partner, cohesin, using chromatin immunoprecipitation coupled with deep sequencing (ChIP-seq) revealded that CTCF globally co-localizes with cohesin.", "Recent genome-wide studies mapping the binding sites of CTCF and its interacting partner, cohesin, using chromatin immunoprecipitation coupled with deep sequencing (ChIP-seq) revealded that CTCF globally co-localizes with cohesin " ]

[ "yes" ]

[ "To investigate cohesin-non-CTCF (CNC) binding events in vivo we mapped cohesin and CTCF, as well as a collection of tissue-specific and ubiquitous transcriptional regulators using ChIP-seq in primary mouse liver.", "In contrast to regions of the genome where cohesin and CTCF colocalize, CNC sites coincide with the binding of master regulators and enhancer-markers and are significantly associated with liver-specific expressed genes.", "Here we report that cohesins colocalize with CTCF at two additional imprinted loci, the Dlk1-Dio3 and the Kcnq1/Kcnq1ot1 loci.", "By use of human hepatocellular carcinoma cells (HepG2), we found that liver-specific transcription factors colocalize with cohesin independently of CTCF at liver-specific targets that are distinct from those found in breast cancer cells", "Because cohesin can colocalize with CTCF, we performed chromatin immunoprecipitation for the cohesin subunit Rad21 and found lineage and stage-specific Rad21 recruitment to CTCF in all Ig loci", "Here we show that zebrafish runx1 is directly bound by cohesin and CCCTC binding factor (CTCF) at the P1 and P2 promoters, and within the intron between P1 and P2.", "The intronic binding sites for cohesin and CTCF coincide with histone modifications that confer enhancer-like properties, and two of the cohesin/CTCF sites behaved as insulators in an in vivo assay", "The identified cohesin and CTCF binding sites are likely to be cis-regulatory elements (CREs) for runx1 since they also recruit RNA polymerase II (RNAPII).", "We have found that CTCF and cohesin are highly enriched at the convergent and partially overlapping transcripts for the LMP1 and LMP2A genes, but it is not yet known how CTCF and cohesin may coordinately regulate these transcripts", "haracterization of constitutive CTCF/cohesin loci: a possible role in establishing topological domains in mammalian genomes", "Our analysis revealed: 1) constitutive CTCF loci were located in constitutive open chromatin and often co-localized with constitutive cohesin loci", "In brain, a third of CTCF and cohesin binding sites coincide, consistent with the potential for many interactions between cohesin and CTCF but also many instances of independent action", "Here, we focus on the emerging roles of CTCF and the cohesin in coordinating long-range interactions between regulatory elements", "Chromatin immunoprecipitation for CTCF and the cohesin subunits RAD21 and SMC3 reveals evolutionarily conserved binding sites within unmethylated regions ∼5 kb downstream of the PLAGL1 differentially methylated region and within the PLAGL1 3' untranslated region (UTR)", "TCF physically links cohesin to chromatin", "ohesin and CTCF: cooperating to control chromosome conformation?", "Recently, three groups mapped numerous cohesin-binding sites in mammalian chromosomes and found substantial overlap with the CCCTC-binding factor (CTCF)", "We found that each site contains a conserved CTCF consensus sequence, binds CTCF, and recruits the cohesin subunit Rad21 in vivo", "Recent experiments have revealed that cohesin binds to the same sites in mammalian genomes as the zinc finger transcription factor CTCF", "Here we review what is known about the roles of cohesin and CTCF in regulating gene expression in mammalian cells, and we discuss how cohesin might mediate the insulator function of CTCF", "Previous studies have shown that this major latency control region is occupied by the cellular chromatin boundary factor CTCF and chromosome structural maintenance proteins SMC1, SMC3, and RAD21, which comprise the cohesin complex", "Cohesin subunits assembled at the CTCF binding sites and bound CTCF proteins in a cell cycle-dependent manner", "We propose that the CTCF-cohesin complex plays a critical role in regulating the cell cycle control of viral gene expression during latency and that failure to maintain cell cycle control of latent transcripts inhibits host cell proliferation and survival", "We used chromosome conformation capture to determine long-range interactions among CTCF/cohesin sites over 2 Mb on human chromosome 11 encompassing the beta-globin locus and flanking olfactory receptor genes", "These results support a genome-wide role for CTCF/cohesin sites through loop formation that both influences transcription and contributes to cell-type-specific chromatin organization and function", "Increased methylation at this promoter triggered the dissociation of the insulator protein CTCF as well as the accompanying cohesin from the BDNF locus", "icotinamide adenine dinucleotide (NAD)-regulated DNA methylation alters CCCTC-binding factor (CTCF)/cohesin binding and transcription at the BDNF locus", "ecent studies have shown that the protein CTCF, which plays an important role in insulation and in large-scale organization of chromatin within the eukaryotic nucleus, depends for both activities on recruitment of the cohesin complex", "We show here that the interaction of CTCF with the cohesin complex involves direct contacts between the cohesin subunit SA2 and specific regions of the C-terminal tail of CTCF", "Taken together, our results demonstrate that specific sites on the C terminus of CTCF are essential for cohesin binding and insulator function", "The only direct interaction between CTCF and cohesin involves contact with SA2, which is external to the cohesin ring", "These numerous CTCF/cohesin sites potentially form the bases of the multiloop rosette structures at the Igh locus that compact during Ig heavy chain rearrangement", "We have previously shown that the Kaposi's Sarcoma-Associated Herpesvirus (KSHV) major latency transcripts encoding LANA, vCyclin, vFLIP, v-miRNAs, and Kaposin are regulated, in part, by a chromatin organizing element that binds CTCF and cohesins", "Mutation of the CTCF-cohesin binding site reduced or eliminated the chromatin conformation linkages, and deregulated viral transcription and genome copy number control", "Our findings indicate that KSHV genomes are organized into chromatin loops mediated by CTCF and cohesin interactions, and that these inter-chromosomal linkages coordinate latent and lytic gene control.", "We show here that GA disrupts an RNA polymerase II (RNAPII) complex that accumulates at the CTCF-cohesin binding site within the first intron of the latency transcript.", "GA altered the enrichment of the RNAPII pausing complex, along with pausing factors SPT5 and NELF-A, at the intragenic CTCF-cohesin binding sites.", "GA treatment also inhibited the transcription of some cellular genes, like c-myc, which contain a similar CTCF-cohesin binding site within the first intron.", "These findings suggest that RNAPII pauses at intragenic CTCF-cohesin binding sites and that abrogation of this pausing by GA leads to loss of proper mRNA production and defects in sister chromatid cohesion, a process important for both viral and cellular chromosome stability.", "TCF and cohesin cooperatively mediate the cell-type specific interchromatin interaction between Bcl11b and Arhgap6 loci", "Additional experiments verified that the interchromatin interaction between the Bcl11b and Arhgap6 loci was cell-type specific, which was cooperatively mediated by CTCF and cohesin.", "enome-wide studies of CCCTC-binding factor (CTCF) and cohesin provide insight into chromatin structure and regulation", "Recent genome-wide studies mapping the binding sites of CTCF and its interacting partner, cohesin, using chromatin immunoprecipitation coupled with deep sequencing (ChIP-seq) revealded that CTCF globally co-localizes with cohesin", "Here, we show by ChIP-Seq that most human subtelomeres contain a CTCF- and cohesin-binding site within ∼1-2 kb of the TTAGGG repeat tract and adjacent to a CpG-islands implicated in TERRA transcription control.", "These findings indicate that CTCF and cohesin are integral components of most human subtelomeres, and important for the regulation of TERRA transcription and telomere end protection", "In addition, we show that this DNA looping requires specific binding of the CTCF/cohesin complex to two symmetrically aligned binding sites in both the transcriptionally active promoters and in one of the enhancers" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/22780989", "http://www.ncbi.nlm.nih.gov/pubmed/23010778", "http://www.ncbi.nlm.nih.gov/pubmed/19158269", "http://www.ncbi.nlm.nih.gov/pubmed/21876668", "http://www.ncbi.nlm.nih.gov/pubmed/19109133", "http://www.ncbi.nlm.nih.gov/pubmed/23295672", "http://www.ncbi.nlm.nih.gov/pubmed/23204437", "http://www.ncbi.nlm.nih.gov/pubmed/18623068", "http://www.ncbi.nlm.nih.gov/pubmed/22550178", "http://www.ncbi.nlm.nih.gov/pubmed/19308701", "http://www.ncbi.nlm.nih.gov/pubmed/21444719", "http://www.ncbi.nlm.nih.gov/pubmed/24257606", "http://www.ncbi.nlm.nih.gov/pubmed/21880767", "http://www.ncbi.nlm.nih.gov/pubmed/21106760", "http://www.ncbi.nlm.nih.gov/pubmed/23804403", "http://www.ncbi.nlm.nih.gov/pubmed/22952237", "http://www.ncbi.nlm.nih.gov/pubmed/19369356", "http://www.ncbi.nlm.nih.gov/pubmed/23498937", "http://www.ncbi.nlm.nih.gov/pubmed/21948239", "http://www.ncbi.nlm.nih.gov/pubmed/21970734", "http://www.ncbi.nlm.nih.gov/pubmed/22440186", "http://www.ncbi.nlm.nih.gov/pubmed/24321385", "http://www.ncbi.nlm.nih.gov/pubmed/20219941", "http://www.ncbi.nlm.nih.gov/pubmed/21628529", "http://www.ncbi.nlm.nih.gov/pubmed/20133600", "http://www.ncbi.nlm.nih.gov/pubmed/21606361", "http://www.ncbi.nlm.nih.gov/pubmed/23945083", "http://www.ncbi.nlm.nih.gov/pubmed/18550811" ]

[]

[ "http://www.uniprot.org/uniprot/CTCF_RAT", "http://www.uniprot.org/uniprot/CTCFL_HUMAN" ]

[ "Bimolecular fluorescence complementation (BiFC) is a powerful method for studying protein-protein interactions in different cell types and organisms. This method was recently developed in the fruit fly Drosophila melanogaster, allowing analyzing protein interaction properties in a physiologically relevant developing context." ]

[ "The study of protein-protein interactions in a physiologically relevant developing context." ]

[ "Bimolecular fluorescence complementation (BiFC) is a powerful method for studying protein-protein interactions in different cell types and organisms. This method was recently developed in the fruit fly Drosophila melanogaster, allowing analyzing protein interaction properties in a physiologically relevant developing context. Here we present a detailed protocol for performing BiFC with the Venus fluorescent protein in live Drosophila embryos, taking the Hox-PBC partnership as an illustrative test case. This protocol applies to any transcription factor and split fluorescent protein in general.", "The understanding of developmental complexity will, therefore, require the characterization of protein interactions within their proper environment. The bimolecular fluorescence complementation (BiFC) technology offers this possibility as it enables the direct visualization of protein interactions in living cells.", "Using a Hox protein partnership as a test case, we investigated the suitability of BiFC for the study of protein interactions in the living Drosophila embryo. Importantly, all BiFC parameters were established with constructs that were stably expressed under the control of endogenous promoters. Under these physiological conditions, we showed that BiFC is specific and sensitive enough to analyse dynamic protein interactions. We next used BiFC in a candidate interaction screen, which led to the identification of several Hox protein partners.", "Using fluorescent proteins, we previously developed a bimolecular fluorescence complementation (BiFC) assay and a multicolor BiFC assay to visualize protein-protein interactions in living cells.", "The bimolecular fluorescence complementation (BiFC) assay represents one of these imaging tools for direct visualization of PPIs in living cells.", "The bimolecular fluorescence complementation (BiFC) assay provides an approach for the visualization of protein interactions and modifications in living cells.", "The bimolecular fluorescence complementation (BiFC) assay provides a direct approach for the visualization of molecular interactions in living cells and organisms.", "The purpose of this protocol is to calculate signal-to-noise (S/N) ratio in the bimolecular fluorescence complementation (BiFC) assay and to provide a semi-quantitative analysis of protein-protein interaction (PPI) in living cells.", "Bimolecular fluorescence complementation (BiFC) analysis enables direct visualization of protein interactions in living cells.", "The bimolecular fluorescence complementation (BiFC) assay has been widely accepted for studying in vivo detection of protein-protein interactions in several organisms.", "Visualization of protein interactions in living Drosophila embryos by the bimolecular fluorescence complementation assay.", "RESULTS: Using a Hox protein partnership as a test case, we investigated the suitability of BiFC for the study of protein interactions in the living Drosophila embryo. ", "Design and implementation of bimolecular fluorescence complementation (BiFC) assays for the visualization of protein interactions in living cells.", "However, its potential has rarely been applied in embryos of animal model organisms and was only performed under transient protein expression levels. RESULTS: Using a Hox protein partnership as a test case, we investigated the suitability of BiFC for the study of protein interactions in the living Drosophila embryo. ", "However, its potential has rarely been applied in embryos of animal model organisms and was only performed under transient protein expression levels. Using a Hox protein partnership as a test case, we investigated the suitability of BiFC for the study of protein interactions in the living Drosophila embryo.", "The bimolecular fluorescence complementation (BiFC) technology offers this possibility as it enables the direct visualization of protein interactions in living cells. However, its potential has rarely been applied in embryos of animal model organisms and was only performed under transient protein expression levels.", "we previously developed a bimolecular fluorescence complementation (BiFC) assay and a multicolor BiFC assay to visualize protein-protein interactions in living cells.", "Using a Hox protein partnership as a test case, we investigated the suitability of BiFC for the study of protein interactions in the living Drosophila embryo.", "Using fluorescent proteins, we previously developed a bimolecular fluorescence complementation (BiFC) assay and a multicolor BiFC assay to visualize protein-protein interactions in living cells." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/16454041", "http://www.ncbi.nlm.nih.gov/pubmed/21276241", "http://www.ncbi.nlm.nih.gov/pubmed/19771334", "http://www.ncbi.nlm.nih.gov/pubmed/18573091", "http://www.ncbi.nlm.nih.gov/pubmed/17406412", "http://www.ncbi.nlm.nih.gov/pubmed/25151172", "http://www.ncbi.nlm.nih.gov/pubmed/23317900", "http://www.ncbi.nlm.nih.gov/pubmed/21091444", "http://www.ncbi.nlm.nih.gov/pubmed/18155474", "http://www.ncbi.nlm.nih.gov/pubmed/17534848" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004330", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004331", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013050", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005453" ]

[ "Hypertrophic cardiomyopathy (HCM) has been recently recognized as the most common inherited cardiovascular disorder, affecting 1 in 500 adults worldwide. HCM is characterized by myocyte hypertrophy resulting in thickening of the ventricular wall, myocyte disarray, interstitial and/or replacement fibrosis, decreased ventricular cavity volume and diastolic dysfunction. HCM is also the most common cause of sudden death in the young particularly among athletes. A large proportion of patients diagnosed with HCM have mutations in sarcomeric proteins. HCM is the most prevalent genetic disorder affecting the heart and is typically inherited in an autosomal dominant pattern. Adults with cardiomyopathy suffer SCD or adverse events such as stroke and heart failure from HCM." ]

[]

[ "Hypertrophic cardiomyopathy (HCM) is a primary disease of the cardiac muscle that occurs mainly due to mutations (>1,400 variants) in genes encoding for the cardiac sarcomere. HCM, the most common familial form of cardiomyopathy, affecting one in every 500 people in the general population, is typically inherited in an autosomal dominant pattern, and presents variable expressivity and age-related penetrance.", "Familial hypertrophic cardiomyopathy (HCM), due to point mutations in genes for sarcomere proteins such as myosin, occurs in 1/500 people and is the most common cause of sudden death in young individuals.", "n HCM, the modified protein function leads, over years to decades, to secondary remodeling with substantial morphological changes, such as hypertrophy, myofibrillar disarray, and extensive fibrosis associated with severe functional deterioration.", "Hypertrophic cardiomyopathy (HCM) is the most common cause of sudden cardiac death (SCD) in the young, particularly among athletes.", "Familial hypertrophic cardiomyopathy (HCM) is one the most common heart disorders, with gene mutations in the cardiac sarcomere.", "Hypertrophic cardiomyopathy (HCM) has been recently recognized as the most common inherited cardiovascular disorder, affecting 1 in 500 adults worldwide. HCM is characterized by myocyte hypertrophy resulting in thickening of the ventricular wall, myocyte disarray, interstitial and/or replacement fibrosis, decreased ventricular cavity volume and diastolic dysfunction. HCM is also the most common cause of sudden death in the young. A large proportion of patients diagnosed with HCM have mutations in sarcomeric proteins.", "Hypertrophic cardiomyopathy (HCM) is a genetic cardiomyopathy. The prevalence of phenotypic expression, in the absence of another systemic or cardiac disease causing increased left ventricular (LV) wall thickness, is estimated to be 1:500. ", "HCM is the most prevalent genetic disorder affecting the heart, it often goes undiagnosed until midlife after patients show symptoms of myocardial remodeling. Adults with cardiomyopathy suffer SCD or adverse events such as stroke and heart failure from HCM.", "Hypertrophic cardiomyopathy (HCM) is a clinically heterogeneous autosomal dominant heart disease characterised by left ventricular hypertrophy in the absence of another cardiac or systemic disease that is capable of producing significant wall thickening.", "Hypertrophic cardiomyopathy (HCM) is an autosomal dominant inherited genetic disease characterized by compensatory pathological left ventricle (LV) hypertrophy due to sarcomere dysfunction.", "Hypertrophic cardiomyopathy (HCM) is a clinically heterogeneous genetic heart disease characterized by left ventricular hypertrophy in the absence of another disease that could explain the wall thickening." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/25044876", "http://www.ncbi.nlm.nih.gov/pubmed/23782526", "http://www.ncbi.nlm.nih.gov/pubmed/25309450", "http://www.ncbi.nlm.nih.gov/pubmed/25191275", "http://www.ncbi.nlm.nih.gov/pubmed/25209314", "http://www.ncbi.nlm.nih.gov/pubmed/25328416", "http://www.ncbi.nlm.nih.gov/pubmed/22665960", "http://www.ncbi.nlm.nih.gov/pubmed/21507890", "http://www.ncbi.nlm.nih.gov/pubmed/25228955", "http://www.ncbi.nlm.nih.gov/pubmed/25081404" ]

[]

[ "http://www.disease-ontology.org/api/metadata/DOID:11984" ]