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HiTZ zentroa 55

[ "Parkinson s disease (PD) is one of the most common degenerative disorders of the central nervous system that produces motor and non-motor symptoms. The majority of cases are idiopathic and characterized by the presence of Lewy bodies containing fibrillar α-synuclein ", "Parkinson's disease (PD) is one of the most common degenerative disorders of the central nervous system that produces motor and non-motor symptoms. The majority of cases are idiopathic and characterized by the presence of Lewy bodies containing fibrillar α-synuclein.", "Parkinsons disease (PD) is one of the most common degenerative disorders of the central nervous system that produces motor and non-motor symptoms. The protein α-synuclein is well recognized to contribute to the pathogenesis of Parkinson disease and is the major component of Lewy bodies and Lewy neurites" ]

[ "Parkinson's disease (PD)" ]

[ "Parkinson's disease (PD) is one of the most common degenerative disorders of the central nervous system that produces motor and non-motor symptoms. The majority of cases are idiopathic and characterized by the presence of Lewy bodies containing fibrillar α-synuclein", "Parkinson's disease is characterized by α-synuclein pathology in the form of Lewy bodies and Lewy neurites", "Parkinson's disease is characterized by neuronal death in the substantia nigra and the presence of intracellular inclusions of α-synuclein in the Lewy bodies", "Parkinson's disease, also known as paralysis agitans, is a progressive degenerative disorder of the central nervous system, with onset usually between the ages of 50 and 65 years, and is associated with loss of dopaminergic neurons in the subsantia nigra and the presence of Lewy bodies", "The protein α-synuclein is well recognized to contribute to the pathogenesis of Parkinson disease and is the major component of Lewy bodies and Lewy neurites", "Parkinson's disease (PD) and related Lewy body diseases are characterized by deposition of α-synuclein aggregates in both the central nervous system and peripheral nervous system.", "Parkinsons disease (PD) and dementia with Lewy bodies are common disorders of the aging population and characterized by the progressive accumulation of �-synuclein (�-syn) in the central nervous system.", "AF-LB and Parkinsons disease (PD) share the neuropathological findings characterized by widely distributed Lewy bodies in the central nervous system including the substantia nigra and locus coeruleus.", "Parkinsons disease (PD) and dementia with Lewy bodies (DLB) are characterized by abnormal deposition of �-synuclein aggregates in many regions of the central and peripheral nervous systems.", "A number of neurodegenerative diseases including Parkinsons disease, dementia with Lewy bodies (DLB) and multiple system atrophy are characterized by the formation and intraneuronal accumulation of fibrillar aggregates of alpha-synuclein (alpha-syn) protein in affected brain regions.", "They have been a long time the hallmark of Parkinsons disease, but in recent years it has emerged that a small group of rare disorders or rare variants of common degenerative diseases are also sometimes associated with Lewy bodies in the nervous system.", "BACKGROUND: Lewy body disease is a heterogeneous group of neurodegenerative disorders characterized by alpha-synuclein accumulation that includes dementia with Lewy bodies (DLB) and Parkinsons Disease (PD).", "Although Parkinsons disease with later dementia (PDD) and dementia with Lewy bodies (DLB) are pathologically characterized by the presence of intraneuronal Lewy inclusion bodies, amyloid deposition is also associated to varying degrees with both these disorders.", "Parkinsons disease (PD) is a neurodegnerative disorder that is pathologically characterized by the presence of Lewy bodies in the brain.", "However, it seems that Braak staging can not explain difference in severity of autonomic failure between DLB and PD. As a possibility, in DLB patients with significant autonomic failure, Lewy bodies may have been localized to the peripheral autonomic nervous system in a long time before onset of dementia or parkinsonism, and propagation of Lewy bodies into the central nervous system may be initiated by apparition of certain promotion factor, such as ageing and amyloid-�.", "Parkinson's disease (PD) is the second most common neurodegenerative disorder that is characterized by two major neuropathological hallmarks: the degeneration of dopaminergic neurons in the substantia nigra (SN) and the presence of Lewy bodies in the surviving SN neurons, as well as other regions of the central and peripheral nervous system", "These include multiple system atrophy (MSA), characterized by accumulation of glial cytoplasmic inclusions, and Lewy body disorders, including Parkinson disease (PD), dementia with Lewy bodies, and the so-called \"pure\" autonomic failure" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/2085926", "http://www.ncbi.nlm.nih.gov/pubmed/22355263", "http://www.ncbi.nlm.nih.gov/pubmed/22251432", "http://www.ncbi.nlm.nih.gov/pubmed/25514659", "http://www.ncbi.nlm.nih.gov/pubmed/23281786", "http://www.ncbi.nlm.nih.gov/pubmed/23979994", "http://www.ncbi.nlm.nih.gov/pubmed/23587141", "http://www.ncbi.nlm.nih.gov/pubmed/24465140", "http://www.ncbi.nlm.nih.gov/pubmed/23225525", "http://www.ncbi.nlm.nih.gov/pubmed/24291999", "http://www.ncbi.nlm.nih.gov/pubmed/19877240", "http://www.ncbi.nlm.nih.gov/pubmed/20174468", "http://www.ncbi.nlm.nih.gov/pubmed/19155272", "http://www.ncbi.nlm.nih.gov/pubmed/23531432", "http://www.ncbi.nlm.nih.gov/pubmed/10986355", "http://www.ncbi.nlm.nih.gov/pubmed/1534893" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D002490", "http://www.disease-ontology.org/api/metadata/DOID:12217", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D002493", "http://www.disease-ontology.org/api/metadata/DOID:331", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D020961" ]

[ "High D1 and D3 activities are present in fetal human liver, and high D1 and mostly absent D3 activities are present in adult human liver." ]

[ "Type 1 deiodinase", "type 3 deiodinase" ]

[ "Iodothyronine deiodinase in vitro activity studies in the chicken showed the presence of type I and type III iodothyronine deiodinase activity in both liver and kidney.", "In embryonic chicken liver (ECL) two types of iodothyronine deiodinases are expressed: D1 and D3.", "In liver homogenates, D1 activity was not correlated with age, whereas D3 activity showed a strong negative correlation with age (r -0.84), with high D3 activities in preterm infants and (except in 1 infant of 35 weeks) absent D3 activity in full-term infants. In microsomes, D1 activities amounted to 4.3-60 pmol/min/mg protein in fetal livers and to 170-313 pmol/min/mg protein in adult livers, whereas microsomal D3 activities were 0.15-1.45 pmol/min/mg protein in fetuses and <0.1 pmol/min/mg protein in all but one adult.", "high D1 and D3 activities in fetal human liver, and high D1 and mostly absent D3 activities in adult human liver." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/9389494", "http://www.ncbi.nlm.nih.gov/pubmed/9794474", "http://www.ncbi.nlm.nih.gov/pubmed/8550759", "http://www.ncbi.nlm.nih.gov/pubmed/9709961", "http://www.ncbi.nlm.nih.gov/pubmed/7629231", "http://www.ncbi.nlm.nih.gov/pubmed/15072569" ]

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[ "The Notch intracellular domain (NICD) forms a transcriptional activation complex with the DNA-binding factor CSL and a transcriptional co-activator of the Mastermind family (MAML). ICN binds to a highly conserved DNA-binding transcription factor called CSL (also known as RBP-Jkappa, CBF1, Suppressor of Hairless, and Lag-1) and recruits Mastermind-like transcriptional co-activators to form a transcriptional activation complex.", "Although it is well understood that N(ICD) forms a transcriptional activation complex, little is known about how the complex is assembled. The Notch intracellular domain (NICD) forms a transcriptional activation complex with the DNA-binding factor CSL and a transcriptional co-activator of the Mastermind family (MAML)." ]

[ "Notch intracellular domain (NICD)", "NICD", "Intracellular part of Notch", "ICN", "NIC", "Transcription factor CSL", "RBP-Jkappa", "CBF1", "Suppressor of Hairless", "Lag-1", "The coactivator protein Mastermind-like 1", "MAML-1" ]

[ "The Notch intracellular domain (NICD) forms a transcriptional activation complex with the DNA-binding factor CSL and a transcriptional co-activator of the Mastermind family (MAML). The \"RAM\" region of NICD recruits Notch to CSL, facilitating the binding of MAML at the interface between the ankyrin (ANK) repeat domain of NICD and CSL.", "Inappropriate release of the intracellular domain of Notch (N(ICD)) from the plasma membrane results in the accumulation of deregulated nuclear N(ICD) that has been linked to human cancers, notably T-cell acute lymphoblastic leukemia (T-ALL). Nuclear N(ICD) forms a transcriptional activation complex by interacting with the coactivator protein Mastermind-like 1 and the DNA binding protein CSL (for CBF-1/Suppressor of Hairless/Lag-1) to regulate target gene expression.", "Although it is well understood that N(ICD) forms a transcriptional activation complex, little is known about how the complex is assembled.", "Canonical Notch signaling is initiated when ligand binding induces proteolytic release of the intracellular part of Notch (ICN) from the cell membrane. ICN then travels into the nucleus where it drives the assembly of a transcriptional activation complex containing the DNA-binding transcription factor CSL, ICN, and a specialized co-activator of the Mastermind family. A consensus DNA binding site motif for the CSL protein was previously defined using selection-based methods, but whether subsequent association of Notch and Mastermind-like proteins affects the DNA binding preferences of CSL has not previously been examined.", "We report here the crystal structure of a Notch transcriptional activation complex containing the ankyrin domain of human Notch1 (ANK), the transcription factor CSL on cognate DNA, and a polypeptide from the coactivator Mastermind-like-1 (MAML-1). ", "Ligand binding by Notch receptors triggers a series of proteolytic cleavages that liberate the intracellular portion of Notch (ICN) from the cell membrane, permitting it to translocate to the nucleus. Nuclear ICN binds to a highly conserved DNA-binding transcription factor called CSL (also known as RBP-Jkappa, CBF1, Suppressor of Hairless, and Lag-1) and recruits Mastermind-like transcriptional co-activators to form a transcriptional activation complex.", "On the basis of our results, we present a working structural model for the organization of the MAML1.ICN.CSL.DNA complex.", "The requirement for cooperative assembly of the MAML1.ICN.CSL.DNA complex suggests that a primary function of ICN is to render CSL competent for MAML loading.", "We report here that the astrogliogenic role of Notch is in part mediated by direct binding of the Notch intracellular domain to the CSL DNA binding protein, forming a transcriptional activation complex onto the astrocyte marker gene, glial fibrillary acidic protein (GFAP).", "Importantly, although the classical CSL-dependent Notch signaling pathway is intact and able to activate the Notch canonical target promoter during the neurogenic phase, it is unable to activate the GFAP promoter during neurogenesis.", "Mastermind (Mam) is a component of Notch pathway signaling. In combination with the intracellular domain of Notch and Suppressor of Hairless, Mam forms a transcriptional activation complex.", "High levels of Notch-mediated transcriptional activation require the formation of a ternary complex consisting of NotchICD, CSL (CBF-1, suppressor of hairless, LAG-1) and a Mastermind family member.", "This function relies on the formation of transcriptional activation complexes that include intracellular Notch, a Mastermind co-activator and the transcription factor CSL bound to cognate DNA.", "This function relies on the formation of transcriptional activation complexes that include intracellular Notch, a Mastermind co-activator and the transcription factor CSL bound to cognate DNA", "High levels of Notch-mediated transcriptional activation require the formation of a ternary complex consisting of NotchICD, CSL (CBF-1, suppressor of hairless, LAG-1) and a Mastermind family member", "NotchIC, together with the transcriptional coactivator Mastermind, form a ternary complex with CSL that activates transcription from genes that are responsive to Notch signaling", "Nuclear N(ICD) forms a transcriptional activation complex by interacting with the coactivator protein Mastermind-like 1 and the DNA binding protein CSL (for CBF-1/Suppressor of Hairless/Lag-1) to regulate target gene expression", "Nuclear ICN binds to a highly conserved DNA-binding transcription factor called CSL (also known as RBP-Jkappa, CBF1, Suppressor of Hairless, and Lag-1) and recruits Mastermind-like transcriptional co-activators to form a transcriptional activation complex" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/20972443", "http://www.ncbi.nlm.nih.gov/pubmed/18758478", "http://www.ncbi.nlm.nih.gov/pubmed/11536431", "http://www.ncbi.nlm.nih.gov/pubmed/20118921", "http://www.ncbi.nlm.nih.gov/pubmed/21124806", "http://www.ncbi.nlm.nih.gov/pubmed/12644465", "http://www.ncbi.nlm.nih.gov/pubmed/12205678", "http://www.ncbi.nlm.nih.gov/pubmed/21245387", "http://www.ncbi.nlm.nih.gov/pubmed/16530044", "http://www.ncbi.nlm.nih.gov/pubmed/22325781" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D015533", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D051880" ]

[ "The variability at each position of the polypeptide chain is defined as:\nVariability = number of different amino acids at a given position / frequency of the most common amino acid at given position." ]

[]

[ "Structural and immunochemical data suggest, however, that V3 contains conserved elements which explain its role in binding to virus co-receptors despite its sequence variability.", "This study, for the first time, describes an in-depth analysis of genetic variation in Vpr using information from global HIV-1 isolates involving a total of 976 Vpr sequences", "We investigated the possible link between enzyme secretion and variability in the linker sequence segment using site-directed mutagenesis and linker domain swapping to construct mutated and chimeric forms of the IgA1 protease from", "We have performed low to high resolution molecular typing to assess the genetic variability of major histocompatibility complex loci (HLA-A, -B, -Cw, -DRB1, and -DQA1) in a large population of European American patients with IIM (n = 571) representing the major myositis autoantibody groups", "In this study, we analyzed the value of IHC versus that of microsatellite instability (MSI) testing in predicting mutation status of the MLH1, MSH2, and MSH6 genes in colorectal carcinomas and adenomas, and explored the frequency and significance of immunohistochemical staining variability", "Computational analyses were used to position the epitope in the context of the virion-associated envelope glycoprotein complex, to determine the variability of the surrounding surface, and to calculate the surface accessibility of possible glycan- and polypeptide-epitope components. ", "ese variations in structure of an expression site for a major, immunoprotective outer membrane protein have important implications for vaccine development and for obtaining an improved understanding of the mechanisms of persistence of ehrlichial infections in humans, domestic animals, and reservoir hosts.", " The V3 region of the isolates used in the neutralization assay was amplified by PCR, directly sequenced, and analyzed to reveal variability between the consensus HIV-1 sequences and the isolates. " ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/12547627", "http://www.ncbi.nlm.nih.gov/pubmed/12072528", "http://www.ncbi.nlm.nih.gov/pubmed/20421997", "http://www.ncbi.nlm.nih.gov/pubmed/11790764", "http://www.ncbi.nlm.nih.gov/pubmed/11292724", "http://www.ncbi.nlm.nih.gov/pubmed/22661385", "http://www.ncbi.nlm.nih.gov/pubmed/17258731", "http://www.ncbi.nlm.nih.gov/pubmed/22863657", "http://www.ncbi.nlm.nih.gov/pubmed/22067045", "http://www.ncbi.nlm.nih.gov/pubmed/8944774", "http://www.ncbi.nlm.nih.gov/pubmed/18721481", "http://www.ncbi.nlm.nih.gov/pubmed/9783696", "http://www.ncbi.nlm.nih.gov/pubmed/16609350", "http://www.ncbi.nlm.nih.gov/pubmed/15613860", "http://www.ncbi.nlm.nih.gov/pubmed/16517887", "http://www.ncbi.nlm.nih.gov/pubmed/17353288", "http://www.ncbi.nlm.nih.gov/pubmed/7511773" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D000917", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D057127", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D000940", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D000906" ]

[ "BACH1, a basic leucine zipper mammalian transcriptional repressor, negatively regulates heme oxygenase 1 (HMOX1), a key cytoprotective enzyme that has antioxidant and anti-inflammatory activities. In the absence of elevated intracellular heme or oxidative stress, BACH1 functions as a repressor of the enhancers of heme oxygenase-1 (HO-1) gene (Hmox-1) by forming heterodimers with the small Maf proteins such as MafK. Bach1 is recruited to a subset of p53 target genes and contributes to impeding p53 action by promoting histone deacetylation.", "BACH1 is, in most contexts, a transcriptional repressor" ]

[ "Repressor" ]

[ "the impact of BACH1 repression on transcription", "Bach1 is a repressor of the oxidative stress response", "transcriptional repressor Bach-1, ", "Bach1, a transcriptional repressor of the HMOX1 gene", "The mechanism underlying Bach1-mediated HO-1 repression is less well understood", "Transcription factor BACH1 [BTB (broad-complex, tramtrack and bric-a-brac) and CNC (cap'n'collar protein) homology 1] binds to ARE-like sequences, functioning as a transcriptional repressor ", "Bach1) is a transcriptional repressor of heme oxygenase-1 (HO-1)", " its regulatory mechanism by the transcriptional repressor, BTB and CNC homology 1 (Bach1),", "Bach1, a basic leucine zipper mammalian transcriptional repressor, negatively regulates heme oxygenase 1 (HMOX1),", "Bach1, the negative regulator of Nrf2", "ach1 is a transcriptional repressor of the heme oxygenase (HO)-1 gene. ", "The inhibitory role for Bach1 may stem from its activity to repress gene expression including HO-1", "Bach1 is a transcriptional repressor of the HO-1 gene (Hmox-1)", "Here we show that the transcription factor Bach1 (BTB and CNC homology 1, basic leucine zipper transcription factor 1), which inhibits oxidative stress-inducible genes, is a crucial negative regulator of oxidative stress-induced cellular senescence", "Bach1 is a transcriptional repressor of the HO-1 gene", "Bach1 repressively controls myocardial HO-1 expression ", " the transcriptional repressor BACH1 binds ARE-like enhancers", " transcription factor Bach1 functions as a repressor of the enhancers of heme oxygenase-1 (HO-1) gene (Hmox-1)", "Bach1, a transcription factor that suppresses the HO-1 gene", "Bach1, a transcriptional repressor that is negatively regulated by heme in mammalian cells", "Bach1 normally represses HO-1 expression. ", "Bach1, a heme binding protein that represses gene expression", "complexes with Bach1 repress MARE-dependent gene expression", "transcriptional repressor Bach1", "bach1-ablation resulted in increased expression of HO-1 ", "Bach1 contributes to the down-regulation of ARE-regulated genes", "evidence that BACH1 acts as a transcriptional repressor in the regulation of MARE-dependent genes", "Bach1 forms a heterodimer with small Maf family, and functions as a repressor of the Maf recognition element (MARE) in vivo", "ach1 is a transcriptional repressor of heme oxygenase-1 and beta-globin genes,", "BACH1 suppresses expression of HO1", "transcription factor Bach1 heterodimerizes with small Maf proteins to repress Maf recognition element (MARE)-dependent gene expression", " Bach1 as a heme-regulated and hypoxia-inducible repressor for transcription of the HO-1 gene", "Bach1, a transcriptional repressor of heme oxygenase-1 gene", "Bach1, a heme-regulated transcriptional repressor", "a heme-binding factor, Bach1, is a critical physiological repressor of ho-1", "transcription repressor Bach1" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/23738048", "http://www.ncbi.nlm.nih.gov/pubmed/23181164", "http://www.ncbi.nlm.nih.gov/pubmed/17257585", "http://www.ncbi.nlm.nih.gov/pubmed/12511571", "http://www.ncbi.nlm.nih.gov/pubmed/15809329", "http://www.ncbi.nlm.nih.gov/pubmed/18426999", "http://www.ncbi.nlm.nih.gov/pubmed/23562577", "http://www.ncbi.nlm.nih.gov/pubmed/14660636", "http://www.ncbi.nlm.nih.gov/pubmed/24035498", "http://www.ncbi.nlm.nih.gov/pubmed/15613547", "http://www.ncbi.nlm.nih.gov/pubmed/19439223", "http://www.ncbi.nlm.nih.gov/pubmed/19011633", "http://www.ncbi.nlm.nih.gov/pubmed/17701549", "http://www.ncbi.nlm.nih.gov/pubmed/16824198", "http://www.ncbi.nlm.nih.gov/pubmed/15068251", "http://www.ncbi.nlm.nih.gov/pubmed/11387216", "http://www.ncbi.nlm.nih.gov/pubmed/22698995", "http://www.ncbi.nlm.nih.gov/pubmed/11530014", "http://www.ncbi.nlm.nih.gov/pubmed/21373270", "http://www.ncbi.nlm.nih.gov/pubmed/18325350", "http://www.ncbi.nlm.nih.gov/pubmed/20388958", "http://www.ncbi.nlm.nih.gov/pubmed/15464985", "http://www.ncbi.nlm.nih.gov/pubmed/16530877", "http://www.ncbi.nlm.nih.gov/pubmed/23880309", "http://www.ncbi.nlm.nih.gov/pubmed/16724942", "http://www.ncbi.nlm.nih.gov/pubmed/20501657", "http://www.ncbi.nlm.nih.gov/pubmed/16487043", "http://www.ncbi.nlm.nih.gov/pubmed/18948842", "http://www.ncbi.nlm.nih.gov/pubmed/21555518", "http://www.ncbi.nlm.nih.gov/pubmed/20345481", "http://www.ncbi.nlm.nih.gov/pubmed/17901053", "http://www.ncbi.nlm.nih.gov/pubmed/19282658", "http://www.ncbi.nlm.nih.gov/pubmed/19035757", "http://www.ncbi.nlm.nih.gov/pubmed/18550526", "http://www.ncbi.nlm.nih.gov/pubmed/16894358", "http://www.ncbi.nlm.nih.gov/pubmed/23446334", "http://www.ncbi.nlm.nih.gov/pubmed/15743416", "http://www.ncbi.nlm.nih.gov/pubmed/17682061", "http://www.ncbi.nlm.nih.gov/pubmed/19119918", "http://www.ncbi.nlm.nih.gov/pubmed/18555605", "http://www.ncbi.nlm.nih.gov/pubmed/22847612", "http://www.ncbi.nlm.nih.gov/pubmed/17942419", "http://www.ncbi.nlm.nih.gov/pubmed/22289179", "http://www.ncbi.nlm.nih.gov/pubmed/21982894", "http://www.ncbi.nlm.nih.gov/pubmed/20127796", "http://www.ncbi.nlm.nih.gov/pubmed/14580148", "http://www.ncbi.nlm.nih.gov/pubmed/22107958", "http://www.ncbi.nlm.nih.gov/pubmed/15855052", "http://www.ncbi.nlm.nih.gov/pubmed/22735309", "http://www.ncbi.nlm.nih.gov/pubmed/15175654", "http://www.ncbi.nlm.nih.gov/pubmed/22127667", "http://www.ncbi.nlm.nih.gov/pubmed/21812759", "http://www.ncbi.nlm.nih.gov/pubmed/15734732", "http://www.ncbi.nlm.nih.gov/pubmed/14504288", "http://www.ncbi.nlm.nih.gov/pubmed/19591297", "http://www.ncbi.nlm.nih.gov/pubmed/16771696", "http://www.ncbi.nlm.nih.gov/pubmed/12356737", "http://www.ncbi.nlm.nih.gov/pubmed/19897490", "http://www.ncbi.nlm.nih.gov/pubmed/21473739" ]

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[ "http://www.uniprot.org/uniprot/BACH1_MOUSE", "http://www.uniprot.org/uniprot/FANCJ_HUMAN", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0006351", "http://www.uniprot.org/uniprot/CODY_LACLA", "http://www.uniprot.org/uniprot/FANCJ_MOUSE", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D050976", "http://www.uniprot.org/uniprot/BACH1_HUMAN" ]

[ "Yes, Kanzaki disease is attributable to a deficiency in alpha-N-acetylgalactosaminidase, which hydrolyzes GalNAcalpha1-O-Ser/Thr." ]

[ "yes" ]

[ "Kanzaki disease (OMIM#104170) is attributable to a deficiency in alpha-N-acetylgalactosaminidase (alpha-NAGA; E.C.3.2.1.49), which hydrolyzes GalNAcalpha1-O-Ser/Thr. ", " Our findings suggest that the association of alpha-NAGA with its substrates is strongly affected by the amino acid substitution at R329 and that the association with GalNAcalpha1-O-Thr is more highly susceptible to structural changes. The residual mutant enzyme in R329W could not associate with GalNAcalpha1-O-Thr and GalNAcalpha1-O-Ser. However, the residual mutant enzyme in R329Q catalyzed GalNAcalpha1-O-Ser to some extent. Therefore, the urinary ratio of GalNAcalpha1-O-Ser:GalNAcalpha1-O-Thr was lower and the clinical phenotype was milder in the R329Q mutation. ", "Kanzaki disease (OMIM#104170) is attributable to a deficiency in alpha-N-acetylgalactosaminidase (alpha-NAGA; E.C.3.2.1.49), which hydrolyzes GalNAcalpha1-O-Ser/Thr.", "Alpha-N-acetylgalactosaminidase (alpha-NAGA) deficiency (Schindler/Kanzaki disease) is a clinically and pathologically heterogeneous genetic disease with a wide spectrum including an early onset neuroaxonal dystrophy (Schindler disease) and late onset angiokeratoma corporis diffusum (Kanzaki disease).", "Structural and immunocytochemical studies on alpha-N-acetylgalactosaminidase deficiency (Schindler/Kanzaki disease).", "We describe the neurologic findings in a patient with alpha-N-acetylgalactosaminidase deficiency (Kanzaki disease).", "Three dimensional structural studies of alpha-N-acetylgalactosaminidase (alpha-NAGA) in alpha-NAGA deficiency (Kanzaki disease): different gene mutations cause peculiar structural changes in alpha-NAGAs resulting in different substrate specificities and clinical phenotypes.", "alpha-N-acetylgalactosaminidase (alpha-NAGA) deficiency is a rare hereditary lysosomal storage disease, and only three alpha-NAGA-deficient patients with angiokeratoma corporis diffusum (Kanzaki) have been described.", "Schindler disease and Kanzaki disease are caused by a deficient lysosomal enzyme, alpha-N-acetylgalactosaminidase (E.C.3.2.1.49).", "The 1.9 a structure of human alpha-N-acetylgalactosaminidase: The molecular basis of Schindler and Kanzaki diseases.", "These data suggest that a prototype of alpha-NAGA deficiency in Kanzaki disease and factors other than the defect of alpha-NAGA may contribute to severe neurological disorders, and Kanzaki disease is thought to be caused by a single enzyme deficiency.", "Alpha-N-acetylgalactosaminidase (alpha-NAGA) deficiency (Schindler/Kanzaki disease) is a clinically and pathologically heterogeneous genetic disease with a wide spectrum including an early onset neuroaxonal dystrophy (Schindler disease) and late onset angiokeratoma corporis diffusum (Kanzaki disease). ", "alpha-N-acetylgalactosaminidase (alpha-NAGA) deficiency is a rare hereditary lysosomal storage disease, and only three alpha-NAGA-deficient patients with angiokeratoma corporis diffusum (Kanzaki) have been described. ", "Kanzaki disease (OMIM#104170) is attributable to a deficiency in alpha-N-acetylgalactosaminidase (alpha-NAGA; E.C.3.2.1.49), which hydrolyzes GalNAcalpha1-O-Ser/Thr. Missense mutations, R329W or R329Q were identified in two Japanese Kanzaki patients.", "Alpha-N-acetylgalactosaminidase (alpha-NAGA) deficiency (Schindler/Kanzaki disease) is a clinically and pathologically heterogeneous genetic disease with a wide spectrum including an early onset neuroaxonal dystrophy (Schindler disease) and late onset angiokeratoma corporis diffusum (Kanzaki disease).", "Kanzaki disease (OMIM#104170) is attributable to a deficiency in alpha-N-acetylgalactosaminidase (alpha-NAGA; E.C.3.2.1.49),", "Kanzaki disease (OMIM#104170) is attributable to a deficiency in alpha-N-acetylgalactosaminidase (alpha-NAGA; E.C.3.2.1.49), which hydrolyzes GalNAcalpha1-O-Ser/Thr.", "alpha-N-acetylgalactosaminidase (alpha-NAGA) deficiency is a rare hereditary lysosomal storage disease, and only three alpha-NAGA-deficient patients with angiokeratoma corporis diffusum (Kanzaki) have been described." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/11251574", "http://www.ncbi.nlm.nih.gov/pubmed/14685826", "http://www.ncbi.nlm.nih.gov/pubmed/19683538", "http://www.ncbi.nlm.nih.gov/pubmed/8577046", "http://www.ncbi.nlm.nih.gov/pubmed/15136691", "http://www.ncbi.nlm.nih.gov/pubmed/15619430" ]

[]

[ "http://www.uniprot.org/uniprot/NAGAB_CHICK", "http://www.uniprot.org/uniprot/NAGAB_BOSIN", "http://www.uniprot.org/uniprot/NAGAB_RAT", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D048809", "http://www.uniprot.org/uniprot/G1092_BACFN", "http://www.uniprot.org/uniprot/GH109_ELIME", "http://www.uniprot.org/uniprot/GH109_SHEON", "http://www.uniprot.org/uniprot/NAGAB_HUMAN" ]

[ "Mycobacterium avium causes disseminated infection in patients with acquired immune deficiency syndrome. M tuberculosis disease is preventable and curable and yet communicable, physicians should maintain a high degree of suspicion for tuberculosis in HIV-infected adults. In comparison, the goal of treating M avium complex in patients with advanced HIV disease is to reduce constitutional symptoms and improve survival. Patients who were suspected to have disseminated mycobacterial infection, presenting fever and (preferably) a CD4 T cell count<100.0 cell/mL were investigated. Twelve (15%) of the 80 blood cultures were positive for mycobacteria, with Mycobacterium avium being identified in 7 (8.8%) samples and M. tuberculosis in 5 (6.2%). The antimycobacterial activities of RS-112997, RS-124922 and RS-118641, three capuramycin analogues that inhibit phospho-N-acetylmuramyl-pentapeptide translocase, were tested against clinical isolates of Mycobacterium tuberculosis, Mycobacterium avium and Mycobacterium intracellulare. The MIC50/90 (mg/L) results for RS-118641 were: M. tuberculosis, 1/2; multidrug-resistant (MDR) M. tuberculosis, 0.5/2; M. avium, 4/8; and M. intracellulare, 0.06/0.5" ]

[ "yes" ]

[ "The prevalence of MAC lung infection in two inner city hospitals was four times higher than that of TB.", "Most patients with combined infection were clinically consistent with MTB and responded to anti MTB treatment alone.", "The triplex PCR developed by us could be used to detect and differentiate M. tuberculosis, M. avium and other mycobacteria in a single reaction tube.", "Twelve (15%) of the 80 blood cultures were positive for mycobacteria, with Mycobacterium avium being identified in 7 (8.8%) samples and M. tuberculosis in 5 (6.2%). ", "The antimycobacterial activities of RS-112997, RS-124922 and RS-118641, three capuramycin analogues that inhibit phospho-N-acetylmuramyl-pentapeptide translocase, were tested against clinical isolates of Mycobacterium tuberculosis, Mycobacterium avium and Mycobacterium intracellulare", "The MIC50/90 (mg/L) results for RS-118641 were: M. tuberculosis, 1/2; multidrug-resistant (MDR) M. tuberculosis, 0.5/2; M. avium, 4/8; and M. intracellulare, 0.06/0.5", "These results suggest that capuramycin analogues exhibit strong antimycobacterial potential and should be considered for further evaluation in the treatment of M. tuberculosis and M. avium-M. intracellulare complex infections in humans.", "Mycobacterium avium causes disseminated infection in patients with acquired immune deficiency syndrome.", "Overall incidences of Mycobacterium tuberculosis (TB) and Mycobacterium avium complex (MAC) were 0.8 and 1.4 cases/100 person-years of follow-up (PYF), decreasing from 1.8 (TB) and 3.5 cases/100 PYF (MAC) before September 1995 to 0.3 and 0.2 cases/100 PYF after March 1997.", "Because M tuberculosis disease is preventable and curable and yet communicable, physicians should maintain a high degree of suspicion for tuberculosis in HIV-infected adults. In comparison, the goal of treating M avium complex in patients with advanced HIV disease is to reduce constitutional symptoms and improve survival.", "MAC pulmonary disease should be considered in the differential diagnosis of SPNs, even when encountered in geographic regions with a high prevalence of pulmonary tuberculosis.", "From April 2001 to February 2002, 80 blood samples from patients who were suspected to have disseminated mycobacterial infection, presenting fever and (preferably) a CD4 T cell count<100.0 cell/mL were investigated", "IL-10 underlies distinct susceptibility of BALB/c and C57BL/6 mice to Mycobacterium avium infection and influences efficacy of antibiotic therapy.", "Clinical utility of rifabutin 1 (RBT), a potent antibiotic used in multidrug regimens for tuberculosis (TB) as well as for infections caused by Mycobacterium avium complex (MAC), has been hampered due to dose-limiting toxicity. ", "Effective therapeutic regimens exist that are limited by the emergence of drug resistance and the inability of antibiotics to kill dormant organisms. ", "Clinical utility of rifabutin 1 (RBT), a potent antibiotic used in multidrug regimens for tuberculosis (TB) as well as for infections caused by Mycobacterium avium complex (MAC), has been hampered due to dose-limiting toxicity.", "a potent antibiotic used in multidrug regimens for tuberculosis (TB) as well as for infections caused by Mycobacterium avium complex (MAC),", "Clinical utility of rifabutin 1 (RBT), a potent antibiotic used in multidrug regimens for tuberculosis (TB) as well as for infections caused by Mycobacterium avium complex (MAC), has been hampered due to dose-limiting toxicity.", "tuberculosis appear to have different genetic mechanisms for resisting the effects of these antibiotics, with pks12 playing a relatively more significant role in MAC." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/19956964", "http://www.ncbi.nlm.nih.gov/pubmed/21258569", "http://www.ncbi.nlm.nih.gov/pubmed/16410940", "http://www.ncbi.nlm.nih.gov/pubmed/15328105", "http://www.ncbi.nlm.nih.gov/pubmed/17548640", "http://www.ncbi.nlm.nih.gov/pubmed/19302308", "http://www.ncbi.nlm.nih.gov/pubmed/10988097", "http://www.ncbi.nlm.nih.gov/pubmed/15347635", "http://www.ncbi.nlm.nih.gov/pubmed/12355367", "http://www.ncbi.nlm.nih.gov/pubmed/17897062", "http://www.ncbi.nlm.nih.gov/pubmed/1441463", "http://www.ncbi.nlm.nih.gov/pubmed/19119013" ]

[]

[]

[ "Suvorexant is a dual orexin receptor antagonist for the treatment of sleep onset and sleep maintenance insomnia." ]

[ "orexin" ]

[ "Suvorexant is the first DORA to be approved and has demonstrated efficacy at decreasing both time to sleep onset and increasing total sleep time compared with placebo. ", "Suvorexant: a dual orexin receptor antagonist for the treatment of sleep onset and sleep maintenance insomnia.", "CONCLUSION: Suvorexant is the first dual orexin receptor antagonist approved for the treatment of insomnia. ", "Crystal structure of the human OX2 orexin receptor bound to the insomnia drug suvorexant.", " The human OX2 receptor (OX2R) belongs to the β branch of the rhodopsin family of GPCRs, and can bind to diverse compounds including the native agonist peptides orexin-A and orexin-B and the potent therapeutic inhibitor suvorexant. ", "Orexin receptor antagonism for treatment of insomnia: a randomized clinical trial of suvorexant.", "Promotion of sleep by suvorexant-a novel dual orexin receptor antagonist.", "The neurotransmitter systems on which the development of these agents were based included serotonin for ondansetron and lorcaserin, dopamine for varenicline, substance P (or neurokinin) for aprepitant, melatonin for ramelteon, and orexin for suvorexant. The indications were chemotherapy-induced nausea and vomiting for ondansetron and aprepitant, smoking cessation for varenicline, weight loss for lorcaserin, and insomnia for suvorexant and ramelteon.", "Suvorexant, a dual orexin receptor antagonist for the management of insomnia.", "Suvorexant, a dual orexin receptor antagonist for the management of insomnia.", "The orexin-1 and orexin-2 receptors are two G protein-coupled receptors that bind the neuropeptides orexin-A and orexin-B. Dual antagonism of the receptors by small molecules is clinically efficacious in the treatment of insomnia, where the most advanced molecule suvorexant has recently been approved.", "Suvorexant helps in decreasing wakefulness by counteracting orexin activity.", " The orexin-1 and orexin-2 receptors are two G protein-coupled receptors that bind the neuropeptides orexin-A and orexin-B. Dual antagonism of the receptors by small molecules is clinically efficacious in the treatment of insomnia, where the most advanced molecule suvorexant has recently been approved.", "Hypnotic drug development has arguably become more focused in recent years, particularly upon the highly anticipated novel target, the orexin (hypocretin) system. Merck&apos;s suvorexant (MK-4305) is the first compound of the so-called dual orexin receptor antagonist (DORA) class expected to be submitted for FDA approval, with a new drug application anticipated in 2012." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/22920041", "http://www.ncbi.nlm.nih.gov/pubmed/25489915", "http://www.ncbi.nlm.nih.gov/pubmed/25406050", "http://www.ncbi.nlm.nih.gov/pubmed/25533960", "http://www.ncbi.nlm.nih.gov/pubmed/23197752", "http://www.ncbi.nlm.nih.gov/pubmed/25667197", "http://www.ncbi.nlm.nih.gov/pubmed/21473737", "http://www.ncbi.nlm.nih.gov/pubmed/24757363", "http://www.ncbi.nlm.nih.gov/pubmed/25397996", "http://www.ncbi.nlm.nih.gov/pubmed/26478806" ]

[]

[]

[ "The oral antidiabetes agent, empagliflozin, can be used as monotherapy or alongside other glucose-lowering treatments, including insulin, to treat T2DM." ]

[ "type 2 diabetes mellitus" ]

[ "Empagliflozin, an SGLT2 inhibitor for the treatment of type 2 diabetes mellitus: a review of the evidence.", "To review available studies of empagliflozin, a sodium glucose co-transporter-2 (SGLT2) inhibitor approved in 2014 by the European Commission and the United States Food and Drug Administration for the treatment of type 2 diabetes mellitus (T2DM).", "In Phase II trials in patients with type 2 diabetes, empagliflozin provided improvements in glycosylated hemoglobin (HbA1c) and other measures of glycemic control when given as monotherapy or add-on to metformin, as well as reductions in weight and systolic blood pressure.", "Empagliflozin: a review of its use in patients with type 2 diabetes mellitus.", "This article reviews the pharmacological properties and clinical use of empagliflozin in patients with type 2 diabetes.", "Empagliflozin: a new sodium-glucose co-transporter 2 (SGLT2) inhibitor for the treatment of type 2 diabetes.", "To evaluate the pharmacodynamics, pharmacokinetics, safety and tolerability of empagliflozin in Japanese patients with type 2 diabetes mellitus.", "A Phase IIb, randomized, placebo-controlled study of the SGLT2 inhibitor empagliflozin in patients with type 2 diabetes.", "Pharmacokinetics, pharmacodynamics, safety and tolerability of 4 weeks' treatment with empagliflozin in Japanese patients with type 2 diabetes mellitus.", "We assessed the efficacy and safety of empagliflozin as an add-on treatment in patients with type 2 diabetes and CKD.", "The SGLT-2 inhibitor empagliflozin improves glucose control, body weight and blood pressure when used as monotherapy or add-on to other antihyperglycemic agents in patients with type 2 diabetes", "Data from five randomized, placebo-controlled, multiple oral dose studies of empagliflozin in patients with type 2 diabetes mellitus (T2DM; N = 974; 1-100 mg q.d.; ≤12 weeks) were used to develop a population pharmacokinetic (PK) model for empagliflozin", "Empagliflozin, (2S,3R,4R,5S,6R)-2-[4-chloro-3-[[4-[(3S)-oxolan-3-yl]oxyphenyl]methyl]phenyl]-6-(hydroxymethyl)oxane-3,4,5-triol was recently approved by the FDA for the treatment of chronic type 2 diabetes mellitus", "The SGLT2 inhibitor empagliflozin has gained approval in the EU and in the USA for the treatment of adults with T2DM (there is no current indication in type 1 diabetes)", "Pharmacokinetics, pharmacodynamics, safety and tolerability of 4 weeks&apos; treatment with empagliflozin in Japanese patients with type 2 diabetes mellitus", "The SGLT-2 inhibitor empagliflozin improves glucose control, body weight and blood pressure when used as monotherapy or add-on to other antihyperglycemic agents in patients with type 2 diabetes. ", "Efficacy and safety of empagliflozin, a sodium glucose cotransporter 2 (SGLT2) inhibitor, as add-on to metformin in type 2 diabetes with mild hyperglycaemia.", "The SGLT2 inhibitor empagliflozin ameliorates early features of diabetic nephropathy in BTBR ob/ob type 2 diabetic mice with and without hypertension.", "Rationale, design and baseline characteristics of a 4-year (208-week) phase III trial of empagliflozin, an SGLT2 inhibitor, versus glimepiride as add-on to metformin in patients with type 2 diabetes mellitus with insufficient glycemic control.", "Exposure-response modelling for empagliflozin, a sodium glucose cotransporter 2 (SGLT2) inhibitor, in patients with type 2 diabetes.", "This article reviews the pharmacological properties and clinical use of empagliflozin in patients with type 2 diabetes.", "With its insulin-independent mechanism of action, empagliflozin monotherapy or combination therapy with other antidiabetic drugs, including insulin, provides a useful addition to the therapeutic options for the management of type 2 diabetes.", "In several phase III trials (104weeks' duration; typically 24weeks' duration) and extension studies (typically76weeks' treatment), empagliflozin monotherapy or add-on therapy to other antihyperglycaemics, including insulin, improved glycaemic control and reduced bodyweight and systolic blood pressure in adult patients with type 2 diabetes.", "Oral empagliflozin (Jardiance()), a sodium glucose cotransporter-2 (SGLT2) inhibitor, is a convenient once-daily treatment for adult patients with type 2 diabetes mellitus.", "Sodium glucose cotransporter 2 (SGLT2) inhibitors are a new class of treatment for T2DM that reduce hyperglycemia by reducing renal glucose reabsorption and thereby increasing urinary glucose excretion.This paper reviews the pharmacokinetic and pharmacodynamic properties of the SGLT2 inhibitor empagliflozin , the results of clinical trials investigating the efficacy of empagliflozin given as monotherapy or as add-on therapy on glycemic control, body weight, and blood pressure in patients with T2DM, and the safety and tolerability profile of empagliflozin.Empagliflozin offers good glycemic efficacy, weight loss, blood pressure reduction, and a low risk of hypoglycemia.", "Empagliflozin for the treatment of type 2 diabetes.", "This paper reviews the pharmacokinetic and pharmacodynamic properties of the SGLT2 inhibitor empagliflozin , the results of clinical trials investigating the efficacy of empagliflozin given as monotherapy or as add-on therapy on glycemic control, body weight, and blood pressure in patients with T2DM, and the safety and tolerability profile of empagliflozin.", "In patients with type 2 diabetes and stage 2 or 3 CKD, empagliflozin reduced HbA1c and was well tolerated. However, our findings might not be applicable to the general population of patients with type 2 diabetes and renal impairment.", "With its insulin-independent mechanism of action, empagliflozin monotherapy or combination therapy with other antidiabetic drugs, including insulin, provides a useful addition to the therapeutic options for the management of type 2 diabetes. This article reviews the pharmacological properties and clinical use of empagliflozin in patients with type 2 diabetes.", "In patients with type 2 diabetes, empagliflozin resulted in dose-dependent, clinically meaningful reductions in HbA1c and FPG, and reductions in body weight compared with placebo. Empagliflozin was well-tolerated with a favourable safety profile.", "No UTIs or genital infections led to premature discontinuation. In patients with type 2 diabetes, empagliflozin resulted in dose-dependent, clinically meaningful reductions in HbA1c and FPG, and reductions in body weight compared with placebo.", "In patients with type 2 diabetes, empagliflozin resulted in dose-dependent, clinically meaningful reductions in HbA1c and FPG, and reductions in body weight compared with placebo.", "In Phase II trials in patients with type 2 diabetes, empagliflozin provided improvements in glycosylated hemoglobin (HbA1c) and other measures of glycemic control when given as monotherapy or add-on to metformin, as well as reductions in weight and systolic blood pressure.", "This article reviews the pharmacological properties and clinical use of empagliflozin in patients with type 2 diabetes.", "A Phase IIb, randomized, placebo-controlled study of the SGLT2 inhibitor empagliflozin in patients with type 2 diabetes.", "Empagliflozin: a review of its use in patients with type 2 diabetes mellitus.", "Empagliflozin: a new sodium-glucose co-transporter 2 (SGLT2) inhibitor for the treatment of type 2 diabetes.", "In patients with type 2 diabetes, empagliflozin-induced glycosuria improved β cell function and insulin sensitivity, despite the fall in insulin secretion and tissue glucose disposal and the rise in EGP after one dose, thereby lowering fasting and postprandial glycemia.", "Single-pill combination therapy for type 2 diabetes mellitus: linagliptin plus empagliflozin." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/23398530", "http://www.ncbi.nlm.nih.gov/pubmed/24943000", "http://www.ncbi.nlm.nih.gov/pubmed/26557225", "http://www.ncbi.nlm.nih.gov/pubmed/25692841", "http://www.ncbi.nlm.nih.gov/pubmed/23906374", "http://www.ncbi.nlm.nih.gov/pubmed/22268612", "http://www.ncbi.nlm.nih.gov/pubmed/24186878", "http://www.ncbi.nlm.nih.gov/pubmed/25598831", "http://www.ncbi.nlm.nih.gov/pubmed/24843716", "http://www.ncbi.nlm.nih.gov/pubmed/24746173", "http://www.ncbi.nlm.nih.gov/pubmed/25712444", "http://www.ncbi.nlm.nih.gov/pubmed/25644093", "http://www.ncbi.nlm.nih.gov/pubmed/24795251", "http://www.ncbi.nlm.nih.gov/pubmed/24991224", "http://www.ncbi.nlm.nih.gov/pubmed/25274537", "http://www.ncbi.nlm.nih.gov/pubmed/25941565", "http://www.ncbi.nlm.nih.gov/pubmed/24944269", "http://www.ncbi.nlm.nih.gov/pubmed/23940010", "http://www.ncbi.nlm.nih.gov/pubmed/25332189", "http://www.ncbi.nlm.nih.gov/pubmed/24964723", "http://www.ncbi.nlm.nih.gov/pubmed/25301180", "http://www.ncbi.nlm.nih.gov/pubmed/24948511", "http://www.ncbi.nlm.nih.gov/pubmed/24622369", "http://www.ncbi.nlm.nih.gov/pubmed/24007456", "http://www.ncbi.nlm.nih.gov/pubmed/24463454", "http://www.ncbi.nlm.nih.gov/pubmed/25775379" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D003924", "http://www.disease-ontology.org/api/metadata/DOID:9352" ]

[ "A pharmacophore describes the arrangement of molecular features a ligand must contain to efficaciously bind a receptor. Pharmacophore models are developed to improve molecular understanding of ligand–protein interactions, and can be used as a tool to identify novel compounds that fulfil the pharmacophore requirements and have a high probability of being biologically active. Protein structure-based pharmacophores (SBPs) derive these molecular features by conversion of protein properties to reciprocal ligand space. Unlike ligand-based pharmacophore models, which require templates of ligands in their bioactive conformation, SBPs do not depend on ligand information." ]

[ "Ligand-based, pharmacophore modeling", "Structure-base, pharmacophore modeling" ]

[ "protein interactions are becoming increasingly significant as potential drug targets; however, the rational identification of small molecule inhibitors of such interactions remains a challenge. Pharmacophore modelling is a popular tool for virtual screening of compound libraries, and has previously been successfully applied to the discovery of enzymatic inhibitors. However, the application of pharmacophore modelling in the field of protein:protein interaction inhibitors has historically been considered more of a challenge and remains limited. In this review, we explore the interaction mimicry by known inhibitors that originate from in vitro screening, demonstrating the validity of pharmacophore mapping in the generation of queries for virtual screening. We discuss the pharmacophore mapping methods that have been successfully employed in the discovery of first-in-class inhibitors. ", " a popular tool for virtual screening of libraries to identify novel active substances that can be potentially developed into drugs. While they have been applied for years on common drug targets, their application in the discovery of protein-protein interaction inhibitors remains limited. This review describes current pharmacophore modelling methods applied in the discovery of novel inhibitors targeting protein-protein interactions. We first address the mimicry of protein-protein interactions with their respective inhibitors as observed in crystal structure complexes. This mimicry can be exploited to derive a pharmacophore query from protein-protein complex structures. We then discuss several cases where pharmacophore queries were utilized for the discovery of first-in-class inhibitors of their respective protein-protein interaction targets.", "The best HypoGen pharmacophore model for ACC2 inhibitors (Hypo1_ACC2) consists of one hydrogen bond acceptor, one hydrophobic aliphatic and one hydrophobic aromatic feature, whereas the best pharmacophore (Hypo1_ACC1) for ACC1 consists of one additional hydrogen-bond donor (HBD) features. The best pharmacophore hypotheses were validated by various methods such as test set, decoy set and Cat-Scramble methodology. The validated pharmacophore models were used to screen several small-molecule databases, including Specs, NCI, ChemDiv and Natural product databases to identify the potential dual ACC inhibitors. The virtual hits were then subjected to several filters such as estimated [Formula: see text] value, quantitative estimation of drug-likeness and molecular docking analysis.", "pharmacophore model has been developed using diverse classes of epidermal growth factor receptor (EGFR) tyrosine kinase (TK) inhibitors useful in the treatment of human tumours. Among the top 10 generated hypotheses, the second hypothesis, with one hydrogen bond acceptor, one ring aromatic and three hydrophobic features, was found to be the best on the basis of Cat Scramble validation as well as test set prediction (r(training) = 0.89, r(test) = 0.82). The model also maps well to the external test set molecules as well as clinically active molecules and corroborates the docking studies. Finally, 10 hits were identified as potential leads after virtual screening of ZINC database for EGFR TK inhibition. ", "In order to clarify the essential structure-activity relationship for the known Aurora-A inhibitors as well as identify new lead compounds against Aurora-A, 3D pharmacophore models were developed based on the known inhibitors. ", "computational methods for molecular design are well established in medicinal chemistry research, their application in the field of natural products is still not exhaustively explored. This article gives a short introduction into both the potential for the application of computer-assisted approaches, such as pharmacophore modelling, virtual screening, docking, and neural networking to efficiently access the bioactive metabolites, and the requirements and limitations related to this specific field. The challenge is which selection criteria and/or multiple filtering tools to apply for a target-oriented isolation of potentially bioactive secondary metabolites. Application examples are provided where in silico tools and classical methods used by natural product scientists are used in an effort to maximize their efficacy in drug discovery. ", "pharmacophore models derived from protein binding site atoms without the inclusion of any ligand information have become more popular in virtual screening studies. However, the accuracy of protein-based pharmacophore models for reproducing the critical protein-ligand interactions has never been explicitly assessed. ", "Our results demonstrate that there are significant variations in the success of protein-based pharmacophore models to reproduce native contacts and consequently native ligand poses dependent on the details of the pharmacophore generation process. We show that the generation of optimized protein-based pharmacophore models is a promising approach for ligand pose prediction and pose rankings", "pharmacophore model does not describe a real molecule or a real association of functional groups but illustrates a molecular recognition of a biological target shared by a group of compounds. Pharmacophores also represent the spatial arrangement of essential interactions in a receptor-binding pocket. Structure based pharmacophores (SBPs) can work both with a free (apo) structure or a macromolecule-ligand complex (holo) structure. The SBP methods that derive pharmacophore from protein-ligand complexes use the potential interactions observed between ligand and protein, whereas, the SBP method that aims to derive pharmacophore from ligand free protein, uses only protein active site information", "3D pharmacophore methods are now commonly used as part of more complex workflows in drug discovery campaigns, and have been successfully and extensively applied in virtual screening (VS) approaches. " ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/23651479", "http://www.ncbi.nlm.nih.gov/pubmed/23651482", "http://www.ncbi.nlm.nih.gov/pubmed/16783689", "http://www.ncbi.nlm.nih.gov/pubmed/22650262", "http://www.ncbi.nlm.nih.gov/pubmed/23651486", "http://www.ncbi.nlm.nih.gov/pubmed/23933279", "http://www.ncbi.nlm.nih.gov/pubmed/15807512", "http://www.ncbi.nlm.nih.gov/pubmed/18410307", "http://www.ncbi.nlm.nih.gov/pubmed/24504131", "http://www.ncbi.nlm.nih.gov/pubmed/23862697", "http://www.ncbi.nlm.nih.gov/pubmed/21521148", "http://www.ncbi.nlm.nih.gov/pubmed/22380004", "http://www.ncbi.nlm.nih.gov/pubmed/16996282", "http://www.ncbi.nlm.nih.gov/pubmed/23621564", "http://www.ncbi.nlm.nih.gov/pubmed/23957390", "http://www.ncbi.nlm.nih.gov/pubmed/20362693", "http://www.ncbi.nlm.nih.gov/pubmed/24266725", "http://www.ncbi.nlm.nih.gov/pubmed/21400356", "http://www.ncbi.nlm.nih.gov/pubmed/23334436", "http://www.ncbi.nlm.nih.gov/pubmed/23675939" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D015195", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D008722" ]

[ "Vertebrate genomes contain thousands of conserved noncoding elements (CNEs) that often function as tissue-specific enhancers. In this study, we have identified CNEs in human, dog, chicken, Xenopus, and four teleost fishes (zebrafish, stickleback, medaka, and fugu) using elephant shark, a cartilaginous vertebrate, as the base genome and investigated the evolution of these ancient vertebrate CNEs (aCNEs) in bony vertebrate lineages ", "Yes. Vertebrate genomes contain thousands of conserved noncoding elements (CNEs) that often function as tissue-specific enhancers. CNEs have been identified, among others, in human, dog, chicken, Xenopus, and four teleost fishes (zebrafish, stickleback, medaka, and fugu)." ]

[ "yes" ]

[ "We report evidence for a mechanism for the maintenance of long-range conserved synteny across vertebrate genomes. We found the largest mammal-teleost conserved chromosomal segments to be spanned by highly conserved noncoding elements (HCNEs), their developmental regulatory target genes, and phylogenetically and functionally unrelated \"bystander\" genes", "After whole genome duplication in teleosts, GRBs, including HCNEs and target genes, were often maintained in both copies, while bystander genes were typically lost from one GRB, strongly suggesting that evolutionary pressure acts to keep the single-copy GRBs of higher vertebrates intact. We show that loss of bystander genes and other mutational events suffered by duplicated GRBs in teleost genomes permits target gene identification and HCNE/target gene assignment", "Vertebrate genomes contain thousands of conserved noncoding elements (CNEs) that often function as tissue-specific enhancers. In this study, we have identified CNEs in human, dog, chicken, Xenopus, and four teleost fishes (zebrafish, stickleback, medaka, and fugu) using elephant shark, a cartilaginous vertebrate, as the base genome and investigated the evolution of these ancient vertebrate CNEs (aCNEs) in bony vertebrate lineages", "This implicates the \"fish-specific\" whole-genome duplication in the accelerated evolution and the loss of a large number of both copies of duplicated CNEs in teleost fishes", "We found zebrafish conserved noncoding elements (CNEs) with pan-vertebrate as well as fish-specific orthologous sequences from across 200 kb of the zebrafish fgf8a genomic regulatory block to direct reporter expression in patterns consistent with the expression pattern of fgf8a", " A significant number of conserved noncoding elements (CNEs) shared between cartilaginous fishes and tetrapods have diverged beyond recognition in teleost fishes. The divergence of CNEs seems to have been initiated in basal ray-finned fishes before the WGD. The fast evolving singleton and duplicated genes as well as the divergent CNEs might have contributed to the diversity of teleost fishes", "We found the largest mammal-teleost conserved chromosomal segments to be spanned by highly conserved noncoding elements (HCNEs), their developmental regulatory target genes, and phylogenetically and functionally unrelated \"bystander\" genes.", "Ancient vertebrate conserved noncoding elements have been evolving rapidly in teleost fishes.", "A significant number of conserved noncoding elements (CNEs) shared between cartilaginous fishes and tetrapods have diverged beyond recognition in teleost fishes.", "We have used a transposon-based transgenic assay in zebrafish to evaluate noncoding sequences at the zebrafish ret locus, conserved among teleosts, and at the human RET locus, conserved among mammals.", "Using computational analysis and exploiting the diversity of teleost genomes, we identified a cluster of highly conserved noncoding sequences surrounding the Six3 gene" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/19095434", "http://www.ncbi.nlm.nih.gov/pubmed/21081479", "http://www.ncbi.nlm.nih.gov/pubmed/19782672", "http://www.ncbi.nlm.nih.gov/pubmed/19562753", "http://www.ncbi.nlm.nih.gov/pubmed/18047696", "http://www.ncbi.nlm.nih.gov/pubmed/17387144", "http://www.ncbi.nlm.nih.gov/pubmed/17617896", "http://www.ncbi.nlm.nih.gov/pubmed/16556802" ]

[]

[]

[ "Using cffDNA from maternal blood, the fetal gender can be determined as early as 6 to 10 weeks of gestation (during the first trimester of pregnancy)." ]

[ "6th to 10th week of gestation", "first trimester of pregnancy" ]

[ "The use of cffDNA in fetal sex determination during the first trimester of pregnancy of female DMD carriers.", "We determined fetal sex during the first trimester using a quantitative real-time polymerase chain reaction (PCR) assay of cffDNA in pregnant carriers of DMD.", "Early fetal gender determination using real-time PCR analysis of cell-free fetal DNA during 6th-10th weeks of gestation.", "Considerable 97.3% sensitivity and 97.3% specificity were obtained in fetal gender determination which is significant in the first trimester of pregnancy.", "Therefore in this study, the probability of detecting sequences on the human Y-chromosome in pregnant women has been evaluated to identify the gender of fetuses. Peripheral blood samples were obtained from 80 pregnant women with gestational age between 6th to 10th weeks and the fetal DNA was extracted from the plasma.", "We evaluated the feasibility and accuracy of non-invasive fetal gender determination using quantitative fluorescent-polymerase chain reaction (QF-PCR) analysis of circulating cffDNA in the first-trimester maternal plasma.", "This study aims to validate a reliable method for non-invasive prenatal diagnosis of fetal gender using maternal plasma cell-free fetal DNA (cffDNA) for fetal sex assessment in the first trimester of pregnancy and test its clinical utility in the diagnosis of potentially affected pregnancies in carriers of X-linked disorders.", "We performed a review of the published literature evaluating the use of cffDNA and ultrasound for prenatal determination of fetal sex during the first trimester of pregnancy.", "The use of cffDNA in fetal sex determination during the first trimester of pregnancy of female DMD carriers", "We performed a review of the published literature evaluating the use of cffDNA and ultrasound for prenatal determination of fetal sex during the first trimester of pregnancy", "Fetal Sex Determination using Non-Invasive Method of Cell-free Fetal DNA in Maternal Plasma of Pregnant Women During 6(th)- 10(th) Weeks of Gestation", "US allows reliable fetal sex determination only during the second trimester. " ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/22261468", "http://www.ncbi.nlm.nih.gov/pubmed/25343090", "http://www.ncbi.nlm.nih.gov/pubmed/14680784", "http://www.ncbi.nlm.nih.gov/pubmed/23690098", "http://www.ncbi.nlm.nih.gov/pubmed/24094458", "http://www.ncbi.nlm.nih.gov/pubmed/11746166", "http://www.ncbi.nlm.nih.gov/pubmed/12661284", "http://www.ncbi.nlm.nih.gov/pubmed/23407464", "http://www.ncbi.nlm.nih.gov/pubmed/22192861" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005333", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D019849", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012732", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012723", "http://amigo.geneontology.org/amigo/term/GO:0030237", "http://amigo.geneontology.org/amigo/term/GO:0007530", "http://amigo.geneontology.org/amigo/term/GO:0030238" ]

[ "Yes, cortical spreading depression appears in ischemic penumbra following ischemic stroke and is associated with expansion of ischemic injury. This has been shown in humans and in animal models." ]

[ "yes" ]

[ "During the subacute phase, the irreversible damage expands into the penumbra: multiple electrical and biological signals are triggered by periinfarct, spreading depression-like depolarizations leading to hypoxia and stepwise increase in lactate.", "Experimental and clinical studies indicate that waves of cortical spreading depolarization (CSD) appearing in the ischemic penumbra contribute to secondary lesion growth.", "Analysis of MCA occlusions (MCAOs) revealed a first CSD wave starting off during ischemic decline at the emerging core region, propagating concentrically over large portions of left cortex.", "Subsequent recurrent waves of CSD did not propagate concentrically but preferentially circled around the ischemic core.", "In the vicinity of the core region, CSDs were coupled to waves of predominantly vasoconstrictive CBF(LSF) responses, resulting in further decline of CBF in the entire inner penumbra and in expansion of the ischemic core.", "We conclude that CSDs and corresponding CBF responses follow a defined spatiotemporal order, and contribute to early evolution of ischemic territories.", "Astrocytes in the metabolically compromised ischemic penumbra-like area showed a long lasting swelling response to spontaneous spreading depolarizations despite rapid dendritic recovery in a photothrombotic occlusion model of focal stroke.", "Spontaneous spreading depolarizations (SDs) occur in the penumbra surrounding ischemic core.", "These SDs, often referred to as peri-infarct depolarizations, cause vasoconstriction and recruitment of the penumbra into the ischemic core in the critical first hours after focal ischemic stroke; however, the real-time spatiotemporal dynamics of SD-induced injury to synaptic circuitry in the penumbra remain unknown.", "We propose that metabolic stress resulting from recurring SDs facilitates acute injury at the level of dendrites and dendritic spines in metabolically compromised tissue, expediting penumbral recruitment into the ischemic core.", "Although the mechanism remains unknown, SDs show delayed electrophysiological recovery within the ischemic penumbra.", "Spreading depression-like peri-infarct depolarizations not only characterize but also worsen penumbra conditions in cortical border zones of experimental focal ischemia.", "We conclude that in focal ischemia, transient peri-infarct depolarizations emerge not only in cortical but also in striatal gray matter, thereby demonstrating the existence of subcortical zones of ischemic penumbra.", "Spreading depression (SD) has been demonstrated following focal ischemia, and the additional workload imposed by SD on a tissue already compromised by a marked reduction in blood flow may contribute to the evolution of irreversible damage in the ischemic penumbra.", "While the changes in the glucose-related metabolites persisted during recovery even in anterior portions of the cortex in both groups in the aftermath of the SD, the magnitude of the changes was greater in the penumbra than in the normal cortex.", "SD appears to impose an equivalent increase in energy demands in control and ischemic brain, but the ability of the penumbra to recover from the insult is compromised.", "Thus, increasing the energy imbalance in the penumbra after multiple SDs may hasten the deterioration of the energy status of the tissue and eventually contribute to terminal depolarization and cell death, particularly in the penumbra.", "It is suggested that the limited survival of the penumbra is due to periinfarct depolarizations, which result in repeated episodes of tissue hypoxia, because the increased metabolic workload is not coupled to an adequate increase of collateral blood supply.", "Transient decreases of the apparent diffusion coefficient (ADC) of water as measured by fast diffusion-weighted imaging (DWI) in the ischemic border zone are thought to reflect cellular swelling associated with spreading depression.", "Severely delayed recovery time after spreading depression is thought to represent the ischemic penumbra.", "One current but controversial hypothesis is that this penumbra tissue often eventually dies because of the metabolic stress imposed by multiple cortical spreading depression (CSD) waves, that is, by ischemic depolarizations.", "After simulated infarction, the model displays the linear relation between final infarct size and the number of CSD waves traversing the penumbra that has been reported experimentally, although damage with each individual wave progresses nonlinearly with time.", "These findings support the hypothesis that CSD waves play an important causal role in the death of ischemic penumbra tissue.", "MCAO also triggers periodic periinfarction depolarizing waves (PIDs) in the ischemic penumbra, the territory of salvage.", "Here, the effects of SD at reduced flow conditions as encountered in the ischemic penumbra are examined.", "The experiments illustrate how peri-infarct depolarizations may detrimentally affect the penumbra.", "In the second series of experiments, periinfarct depolarizations (PIDs) were recorded with an extracellular DC electrode at two locations in the ischemic penumbra for the initial 3 h following MCAO.", "In vivo two-photon microscopy of green fluorescent protein-expressing neurons in this penumbra-like area at risk revealed that SDs were temporally correlated with rapid (<6 s) dendritic beading." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/15078545", "http://www.ncbi.nlm.nih.gov/pubmed/20087371", "http://www.ncbi.nlm.nih.gov/pubmed/9740103", "http://www.ncbi.nlm.nih.gov/pubmed/22821441", "http://www.ncbi.nlm.nih.gov/pubmed/10082816", "http://www.ncbi.nlm.nih.gov/pubmed/14568331", "http://www.ncbi.nlm.nih.gov/pubmed/14759495", "http://www.ncbi.nlm.nih.gov/pubmed/8623122", "http://www.ncbi.nlm.nih.gov/pubmed/15879337", "http://www.ncbi.nlm.nih.gov/pubmed/11450018", "http://www.ncbi.nlm.nih.gov/pubmed/18446167", "http://www.ncbi.nlm.nih.gov/pubmed/7944288", "http://www.ncbi.nlm.nih.gov/pubmed/20700132", "http://www.ncbi.nlm.nih.gov/pubmed/22994218", "http://www.ncbi.nlm.nih.gov/pubmed/20660268", "http://www.ncbi.nlm.nih.gov/pubmed/15703392" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013181", "http://www.disease-ontology.org/api/metadata/DOID:3455", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D020521" ]

[ "Phospholamban (PLB) is a 24- to 27-kDa phosphoprotein that modulates activity of the sarco(endo)plasmic reticulum Ca2+ ATPase (SERCA). Expression of PLB is reportedly limited to cardiac, slow-twitch skeletal and smooth muscle in which PLB is an important regulator of [Ca2+]i and contractility in these muscles.The membrane protein complex between the sarcoplasmic reticulum Ca(2+)-ATPase (SERCA) and phospholamban (PLN) controls Ca(2+) transport in cardiomyocytes, thereby modulating cardiac contractility. β-Adrenergic-stimulated phosphorylation of PLN at Ser-16 enhances SERCA activity via an unknown mechanism.", "Phospholamban (PLN) is a type II membrane protein that inhibits the sarcoplasmic reticulum Ca(2+)-ATPase (SERCA), thereby regulating calcium homeostasis in cardiac muscle. The sarco(endo)plasmic reticulum Ca(2+) ATPase (SERCA) 2a is responsible for Ca(2+) up-take by this organelle and is inhibited in a reversible manner by phospholamban. When PLB is phosphorylated, its inhibitory effect towards SERCA 2a is relieved, leading to an enhanced myocardial performance.Thus, alleviation of phospholamban-mediated inhibition of SERCA2a is a potential therapeutic option for heart failure and cardiomyopathy." ]

[ "yes" ]

[ "The membrane protein complex between the sarcoplasmic reticulum Ca(2+)-ATPase (SERCA) and phospholamban (PLN) controls Ca(2+) transport in cardiomyocytes, thereby modulating cardiac contractility. β-Adrenergic-stimulated phosphorylation of PLN at Ser-16 enhances SERCA activity via an unknown mechanism.", "Phospholamban (PLN) is a type II membrane protein that inhibits the sarcoplasmic reticulum Ca(2+)-ATPase (SERCA), thereby regulating calcium homeostasis in cardiac muscle. In membranes, PLN forms pentamers that have been proposed to function either as a storage for active monomers or as ion channels.", "Regulation of the SERCA calcium pump by phospholamban (PLB) is largely due to interactions between their respective transmembrane domains. In spite of numerous mutagenesis and kinetic studies, we still do not have a clear mechanistic picture of how PLB influences the calcium transport cycle of SERCA.", "Calcium transport across the membrane of the sarcoplasmic reticulum (SR) plays an important role in the regulation of heart muscle contraction and relaxation. The sarco(endo)plasmic reticulum Ca(2+) ATPase (SERCA) 2a is responsible for Ca(2+) up-take by this organelle and is inhibited in a reversible manner by phospholamban, another SR membrane protein. Thus, alleviation of phospholamban-mediated inhibition of SERCA2a is a potential therapeutic option for heart failure and cardiomyopathy.", "Phospholamban has been suggested to be a key regulator of cardiac sarcoplasmic reticulum (SR) Ca cycling and contractility and a potential therapeutic target in restoring the depressed Ca cycling in failing hearts.", "In larger mammals, a higher fraction of SERCA2a pumps are regulated by phospholamban, and this may influence therapeutic strategies to enhance cardiac contractility and functional cardiac reserve.", "Phospholamban (PLB) inhibits the sarcoplasmic reticulum (SR) Ca(2+)-ATPase (SERCA), and this inhibition is relieved by Ca(2+) calmodulin-dependent protein kinase II (CaM kinase II) phosphorylation", "These findings suggest that PLB is an important modulator of gastric antrum smooth muscle contractility by modulation of SR Ca(2+) release and CaM kinase II activity.", "The function of the SERCA pump is modulated by the endogenous molecules phospholamban (PLB) and sarcolipin (SLN), expressed in cardiac and skeletal muscles. The mechanism of action of PLB on SERCA is well characterized, whereas that of SLN is only beginning to be understood. ", " Phospholamban (PLB) is an inhibitor of the sarcoplasmic reticulum (SR) Ca2+-ATPase (SERCA).", "These results show that alteration of the PLB:SERCA ratio can significantly modulate smooth muscle [Ca2+]i.", "Phospholamban expressed in cardiac muscle and sarcolipin expressed in skeletal muscle regulate SERCA activity.", "Phospholamban (PLB) is a 24- to 27-kDa phosphoprotein that modulates activity of the sarco(endo)plasmic reticulum Ca2+ ATPase (SERCA). Expression of PLB is reportedly limited to cardiac, slow-twitch skeletal and smooth muscle in which PLB is an important regulator of [Ca2+]i and contractility in these muscles.", "Regulation of the sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA 2a) depends on the phosphorylation state of phospholamban (PLB). When PLB is phosphorylated, its inhibitory effect towards SERCA 2a is relieved, leading to an enhanced myocardial performance. ", " Ca(2+) reuptake occurs via sarcoendoplasmic reticulum Ca(2+) ATPase (SERCA) and is regulated by the inhibitory protein phospholamban (PLB) in many cell types.", "Phospholamban (PLN) is a small integral membrane protein, which binds and inhibits in a yet unknown fashion the Ca(2+)-ATPase (SERCA) in the sarcoplasmic reticulum.", "Phospholamban (PLN) is the endogenous inhibitor of the sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA), the integral membrane enzyme responsible for 70�% of the removal of Ca(2+) from the cytosol, inducing cardiac muscle relaxation in humans.", "Phospholamban (PLB) is an integral membrane protein regulating Ca(2+) transport through inhibitory interaction with sarco(endo)plasmic reticulum calcium ATPase (SERCA).", "Phosphorylation by protein kinase A and dephosphorylation by protein phosphatase 1 modulate the inhibitory activity of phospholamban (PLN), the endogenous regulator of the sarco(endo)plasmic reticulum calcium Ca(2+) ATPase (SERCA).", "Phosphorylation by protein kinase A and dephosphorylation by protein phosphatase 1 modulate the inhibitory activity of phospholamban (PLN), the endogenous regulator of the sarco(endo)plasmic reticulum calcium Ca(2+) ATPase (SERCA)", "We used EPR spectroscopy to probe directly the interaction between phospholamban (PLB) and its regulatory target, the sarcoplasmic reticulum Ca-ATPase (SERCA)" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/16564056", "http://www.ncbi.nlm.nih.gov/pubmed/23308118", "http://www.ncbi.nlm.nih.gov/pubmed/18045856", "http://www.ncbi.nlm.nih.gov/pubmed/17286271", "http://www.ncbi.nlm.nih.gov/pubmed/19112098", "http://www.ncbi.nlm.nih.gov/pubmed/22971924", "http://www.ncbi.nlm.nih.gov/pubmed/19708671", "http://www.ncbi.nlm.nih.gov/pubmed/9845327", "http://www.ncbi.nlm.nih.gov/pubmed/10024311", "http://www.ncbi.nlm.nih.gov/pubmed/11559781", "http://www.ncbi.nlm.nih.gov/pubmed/19840770", "http://www.ncbi.nlm.nih.gov/pubmed/21576492", "http://www.ncbi.nlm.nih.gov/pubmed/24101520", "http://www.ncbi.nlm.nih.gov/pubmed/10951187", "http://www.ncbi.nlm.nih.gov/pubmed/19395670", "http://www.ncbi.nlm.nih.gov/pubmed/15134458", "http://www.ncbi.nlm.nih.gov/pubmed/19158349" ]

[]

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

[ "To utilize DNA shape information when analysing the DNA binding specificities of TFs, the TFBSshape database was developed for calculating DNA structural features from nucleotide sequences provided by motif databases. The TFBSshape database can be used to generate heat maps and quantitative data for DNA structural features (i.e., minor groove width, roll, propeller twist and helix twist) for 739 TF datasets from 23 different species derived from the motif databases JASPAR and UniPROBE. As demonstrated for the basic helix-loop-helix and homeodomain TF families, TFBSshape database can be used to compare, qualitatively and quantitatively, the DNA binding specificities of closely related TFs and, thus, uncover differential DNA binding specificities that are not apparent from nucleotide sequence alone." ]

[]

[ "TFBSshape: a motif database for DNA shape features of transcription factor binding sites.", "To utilize DNA shape information when analysing the DNA binding specificities of TFs, we developed a new tool, the TFBSshape database (available at http://rohslab.cmb.usc.edu/TFBSshape/), for calculating DNA structural features from nucleotide sequences provided by motif databases. The TFBSshape database can be used to generate heat maps and quantitative data for DNA structural features (i.e., minor groove width, roll, propeller twist and helix twist) for 739 TF datasets from 23 different species derived from the motif databases JASPAR and UniPROBE. As demonstrated for the basic helix-loop-helix and homeodomain TF families, our TFBSshape database can be used to compare, qualitatively and quantitatively, the DNA binding specificities of closely related TFs and, thus, uncover differential DNA binding specificities that are not apparent from nucleotide sequence alone.", "To utilize DNA shape information when analysing the DNA binding specificities of TFs, we developed a new tool, the TFBSshape database (available at http://rohslab.cmb.usc.edu/TFBSshape/), for calculating DNA structural features from nucleotide sequences provided by motif databases.", "The TFBSshape database can be used to generate heat maps and quantitative data for DNA structural features (i.e., minor groove width, roll, propeller twist and helix twist) for 739 TF datasets from 23 different species derived from the motif databases JASPAR and UniPROBE.", "As demonstrated for the basic helix-loop-helix and homeodomain TF families, our TFBSshape database can be used to compare, qualitatively and quantitatively, the DNA binding specificities of closely related TFs and, thus, uncover differential DNA binding specificities that are not apparent from nucleotide sequence alone.", "DNA structural features refine the description of TF binding specificities and provide mechanistic insights into protein-DNA recognition. Existing motif databases contain extensive nucleotide sequences identified in binding experiments based on their selection by a TF. To utilize DNA shape information when analysing the DNA binding specificities of TFs, we developed a new tool, the TFBSshape database (available at http://rohslab.cmb.usc.edu/TFBSshape/), for calculating DNA structural features from nucleotide sequences provided by motif databases. ", "To utilize DNA shape information when analysing the DNA binding specificities of TFs, we developed a new tool, the TFBSshape database (available at http://rohslab.cmb.usc.edu/TFBSshape/), for calculating DNA structural features from nucleotide sequences provided by motif databases. The TFBSshape database can be used to generate heat maps and quantitative data for DNA structural features (i.e., minor groove width, roll, propeller twist and helix twist) for 739 TF datasets from 23 different species derived from the motif databases JASPAR and UniPROBE.", "Existing motif databases contain extensive nucleotide sequences identified in binding experiments based on their selection by a TF. To utilize DNA shape information when analysing the DNA binding specificities of TFs, we developed a new tool, the TFBSshape database (available at http://rohslab.cmb.usc.edu/TFBSshape/), for calculating DNA structural features from nucleotide sequences provided by motif databases.", "The TFBSshape database can be used to generate heat maps and quantitative data for DNA structural features (i.e., minor groove width, roll, propeller twist and helix twist) for 739 TF datasets from 23 different species derived from the motif databases JASPAR and UniPROBE. As demonstrated for the basic helix-loop-helix and homeodomain TF families, our TFBSshape database can be used to compare, qualitatively and quantitatively, the DNA binding specificities of closely related TFs and, thus, uncover differential DNA binding specificities that are not apparent from nucleotide sequence alone.", "As demonstrated for the basic helix-loop-helix and homeodomain TF families, our TFBSshape database can be used to compare, qualitatively and quantitatively, the DNA binding specificities of closely related TFs and, thus, uncover differential DNA binding specificities that are not apparent from nucleotide sequence alone. ." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/24214955" ]

[]

[ "http://amigo.geneontology.org/amigo/term/GO:0051090", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001665" ]

[ "Alpers disease is a fatal neurogenetic disorder first described more than 70 years ago. It is an autosomal recessive, developmental mitochondrial DNA depletion disorder characterized by deficiency in mitochondrial DNA polymerase gamma (POLG) catalytic activity, refractory seizures, neurodegeneration, and liver disease.", "Alpers-Huttenlocher syndrome (AHS) is a very rare autosomal recessive disorder" ]

[ "yes" ]

[ "Alpers-Huttenlocher syndrome (AHS) is a very rare autosomal recessive disorder", "Alpers syndrome is an autosomal recessive mitochondrial DNA depletion disorder that affects children and young adults", "Alpers' syndrome is a fatal neurogenetic disorder first described more than 70 years ago. It is an autosomal recessive, developmental mitochondrial DNA depletion disorder characterized by deficiency in mitochondrial DNA polymerase gamma (POLG) catalytic activity, refractory seizures, neurodegeneration, and liver disease", "Histopathological findings in both patients ((a) chronic hepatitis with prominent bile duct proliferation, fatty change, and fibrosis; (b) in the brain a patchy destruction of the cerebral cortex, predominantly involving striate cortex) were characteristic of progressive neuronal degeneration of childhood with liver disease--Alpers-Huttenlocher syndrome--a rare autosomal recessive disorder usually seen in infants and young children", "Histopathological findings in both patients ((a) chronic hepatitis with prominent bile duct proliferation, fatty change, and fibrosis; (b) in the brain a patchy destruction of the cerebral cortex, predominantly involving striate cortex) were characteristic of progressive neuronal degeneration of childhood with liver disease--Alpers-Huttenlocher syndrome--a rare autosomal recessive disorder usually seen in infants and young children.", "Alpers syndrome is a rare autosomal recessive hepatocerebral degenerative disorder.", "Alpers disease is a recessive mitochondrial disorder caused by mutations in POLG1 and characterized primarily by progressive neurological and hepatic degeneration.", "Alpers syndrome is an autosomal recessive mitochondrial DNA depletion disorder that affects children and young adults.", "We conclude that Alpers disease can be a cause of rapidly progressive liver failure in early childhood. Although the cause of this autosomal recessive disease is not known, it does not appear to be related to peroxisomal dysfunction." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/22000311", "http://www.ncbi.nlm.nih.gov/pubmed/15122711", "http://www.ncbi.nlm.nih.gov/pubmed/22006280", "http://www.ncbi.nlm.nih.gov/pubmed/1861211", "http://www.ncbi.nlm.nih.gov/pubmed/21451360", "http://www.ncbi.nlm.nih.gov/pubmed/16181814", "http://www.ncbi.nlm.nih.gov/pubmed/7897414" ]

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[]

[ "Yes, vemurafenib is highly effective in patients with relapsed or refractory hairy-cell leukemia." ]

[ "yes" ]

[ "CONCLUSIONS: A short oral course of vemurafenib was highly effective in patients with relapsed or refractory hairy-cell leukemia.", "Our results strongly support and inform the clinical use of BRAF and MEK inhibitors in HCL.", "The therapeutic approach of vemurafenib in treatment-refractory hairy cell leukemia is promising and offers an additional treatment option. ", "Successful re-treatment of a relapsed V600E mutated HCL patient with low-dose vemurafenib.", "Recent identification of the recurrent V600E BRAF mutation in a majority of HCL patients has led some teams to evaluate the clinical potential of vemurafenib, a BRAF V600 specific inhibitor in a limited number of refractory HCL patients. Recently, we published the case of an HCL patient successfully treated with a low dose of vemurafenib.", "We present here the successful retreatment of this patient with a second line of vemurafenib. Our data suggest for the first time that vemurafenib at the dose of 240 mg once a day could be sufficient to maintain a complete hematological remission after an initial induction treatment with low-dose vemurafenib (2 × 240 mg) daily without inducing major toxicity.", "The discovery of the BRAF mutation has created a therapeutic target exploited by oral inhibitors like vemurafenib and dabrafenib.", "[Successful use of vemurafenib in a patient with resistant hairy cell leukemia].", "The frequent persistence of phosphorylated ERK-positive leukemic cells in bone marrow at the end of treatment suggests bypass reactivation of MEK and ERK as a resistance mechanism.CONCLUSIONS: A short oral course of vemurafenib was highly effective in patients with relapsed or refractory hairy-cell leukemia. ", "A short oral course of vemurafenib was highly effective in patients with relapsed or refractory hairy-cell leukemia.", "A short oral course of vemurafenib was highly effective in patients with relapsed or refractory hairy-cell leukemia.", "The therapeutic approach of vemurafenib in treatment-refractory hairy cell leukemia is promising and offers an additional treatment option." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/25480661", "http://www.ncbi.nlm.nih.gov/pubmed/25815361", "http://www.ncbi.nlm.nih.gov/pubmed/25148599", "http://www.ncbi.nlm.nih.gov/pubmed/26352686", "http://www.ncbi.nlm.nih.gov/pubmed/24137951", "http://www.ncbi.nlm.nih.gov/pubmed/25774734" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D007943", "http://www.disease-ontology.org/api/metadata/DOID:285" ]

[ "In general, histone methyltransferases (HMTs) have no widely approved high-throughput screening assay format, and therefore reference inhibitors are not available for many of the HMTs. However, there are several selective HMT inhibitors: Trichostatin A (TSA), BIX-01294 and its derivative TM2-115, 2,4-pyridinedicarboxylic acid (2,4-PDCA), 3-deazaneplanocin A (DZNep), Psammaplin A (PsA) and Sulforaphane (SFN)." ]

[ "BIX-01294", "TM2-115", "2,4-pyridinedicarboxylic acid", "2,4-PDCA", "3-deazaneplanocin A", "DZNep", "Trichostatin A", "TSA", "Psammaplin A", "PsA", "Sulforaphane", "SFN" ]

[ "However, in general, HMTs have no widely accepted high-throughput screening (HTS) assay format, and reference inhibitors are not available for many of the enzymes.", "Small-molecule histone methyltransferase inhibitors display rapid antimalarial activity against all blood stage forms in Plasmodium falciparum.", "We synthesized a compound library based upon a known specific inhibitor (BIX-01294) of the human G9a histone methyltransferase. Two compounds, BIX-01294 and its derivative TM2-115, inhibited P. falciparum 3D7 parasites in culture with IC(50) values of ~100 nM, values at least 22-fold more potent than their apparent IC(50) toward two human cell lines and one mouse cell line.", "Together, these results suggest that BIX-01294 and TM2-115 inhibit malaria parasite histone methyltransferases, resulting in rapid and irreversible parasite death.", "Synthesis and structure-activity relationship investigation of adenosine-containing inhibitors of histone methyltransferase DOT1L.", "A total of 55 adenosine-containing compounds were designed and synthesized, among which several potent DOT1L inhibitors were identified with K(i) values as low as 0.5 nM.", "Several new reagents and assays were developed to aid in the identification of EZH2 inhibitors, and these were used to execute two high-throughput screening campaigns.", "Of the five histone methyltransferases known to mediate methylation of the lysine 9 residue of histone H3 (H3K9), euchromatic histone-lysine N-methyltransferase 2 (EHMT2; also known as G9a) has been shown to be a primary mediator of H3K9 dimethylation; BIX-01294 has been shown to be a specific inhibitor of EHMT2", "We hypothesised that inhibition of EHMT2 by BIX-01294 would result in reduced levels of H3K9 dimethylation and compromised embryo development.", "We also demonstrate that peptides that mimic SET1 family Win motif sequences inhibit H3K4 dimethylation by the MLL1 core complex with varying degrees of efficiency.", "Studies of H3K4me3 demethylation by KDM5B/Jarid1B/PLU1 reveals strong substrate recognition in vitro and identifies 2,4-pyridine-dicarboxylic acid as an in vitro and in cell inhibitor.", "Inhibition studies of ccKDM5B showed both in vitro and in cell inhibition of ccKDM5B by 2,4-pyridinedicarboxylic acid (2,4-PDCA) with a potency similar to that reported for the HDM KDM4C.", "Treatment with 3-deazaneplanocin A (DZNep), an inhibitor of H3K27me3 and H4K20me3, significantly enhanced the BZLF1 transcription in Raji cells when in combination with an HDAC inhibitor, trichostatin A (TSA).", "All assays allowed profiling of known SET7/9 and LSD1 inhibitors. The results demonstrate that the optimized LANCE Ultra and AlphaLISA assay formats provide a relevant biochemical screening approach toward the identification of small-molecule inhibitors of HMTs and HDMs that could lead to novel epigenetic therapies.", "Selective inhibitors of histone methyltransferase DOT1L: design, synthesis, and crystallographic studies.", "We used structure- and mechanism-based design to discover several potent inhibitors of DOT1L with IC(50) values as low as 38 nM.", "Inhibition of histone lysine methylation enhances cancer-testis antigen expression in lung cancer cells: implications for adoptive immunotherapy of cancer.", "Short hairpin RNAs were used to inhibit several histone methyltransferases (KMT) and histone demethylases (KDM) that mediate histone methylation and repress gene expression.", "DZNep, a pharmacologic inhibitor of KMT6 expression, recapitulated the effects of KMT6 knockdown.", "Recent evidence shows that S-adenosylhomocysteine (AdoHcy) hydrolase inhibitors (AHI) such as 3-deazaneplanocin A (DZNep) modulate chromatin through indirect inhibition of histone methyltransferases including EZH2. We investigated the biological effects of AdoHcy hydrolase inhibition using DZNep and its structural analogues 3-deazaadenosine (DZA) and neplanocin A (Nep A) in breast cancer cells.", "A chemiluminescence-based method for identification of histone lysine methyltransferase inhibitors.", "The method is particularly well suited for detection of inhibitors acting by the desired histone peptide competitive mechanism and is applicable to testing other HMTs, demonstrated here with the G9a homolog EHMT1, also known as GLP.", "This study reports the pharmacokinetics and tissue distribution of a novel histone deacetylase and DNA methyltransferase inhibitor, psammaplin A (PsA), in mice.", "Human diet contains many histone deacetylase (HDAC) inhibitors, such as the bioactive component sulforaphane (SFN), whose epigenetic effects on MSTN gene in satellite cells are unknown.", "We found that DNA methyltransferase inhibitor (5-Aza-2'-deoxycytidine) and histone deacetylase inhibitor (trichostatin A) reduced leptin receptor expression.", "However, histone deacetylase (HDAC) inhibitors trichostatin A (TSA) and sodium butyrate (NaBt) significantly increased Wnt5a mRNA expression in SW620." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/23557020", "http://www.ncbi.nlm.nih.gov/pubmed/22522911", "http://www.ncbi.nlm.nih.gov/pubmed/22924785", "http://www.ncbi.nlm.nih.gov/pubmed/21940714", "http://www.ncbi.nlm.nih.gov/pubmed/23077658", "http://www.ncbi.nlm.nih.gov/pubmed/23092945", "http://www.ncbi.nlm.nih.gov/pubmed/23139138", "http://www.ncbi.nlm.nih.gov/pubmed/20567762", "http://www.ncbi.nlm.nih.gov/pubmed/23379261", "http://www.ncbi.nlm.nih.gov/pubmed/22357272", "http://www.ncbi.nlm.nih.gov/pubmed/22781932", "http://www.ncbi.nlm.nih.gov/pubmed/23011794", "http://www.ncbi.nlm.nih.gov/pubmed/22964322", "http://www.ncbi.nlm.nih.gov/pubmed/22420752", "http://www.ncbi.nlm.nih.gov/pubmed/19860425", "http://www.ncbi.nlm.nih.gov/pubmed/22560341", "http://www.ncbi.nlm.nih.gov/pubmed/22429326", "http://www.ncbi.nlm.nih.gov/pubmed/22904200", "http://www.ncbi.nlm.nih.gov/pubmed/20556507", "http://www.ncbi.nlm.nih.gov/pubmed/21546573", "http://www.ncbi.nlm.nih.gov/pubmed/21936531", "http://www.ncbi.nlm.nih.gov/pubmed/22665483" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D056572", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0042054" ]

[ "Amyotrophic lateral sclerosis (ALS) is a progressive degeneration of upper and lower motor neurons. ", "Amyotrophic lateral sclerosis (ALS) is a progressive degeneration of upper and lower motor neurons." ]

[]

[ "Motor neuron diseases (MND), such as amyotrophic lateral sclerosis (ALS) and spinal muscular atrophy (SMA), are progressive neurodegenerative diseases that share the common characteristic of upper and/or lower motor neuron degeneration.", "Amyotrophic lateral sclerosis (ALS) is a progressive degeneration of upper and lower motor neurons.", "There are four main hypotheses about the cause of ALS: excitotoxicity linked to glutamate receptor overactivation; mutation of the superoxide dismutase gene; production of autoantibodies to calcium channels; neurofilament accumulation. The motoneuron degeneration characteristic of ALS could be caused by any one or a combination of these mechanisms.", "Amyotrophic lateral sclerosis is the most common adult-onset motor neuron disease and evidence from mice expressing amyotrophic lateral sclerosis-causing SOD1 mutations suggest that neurodegeneration is a non-cell autonomous process where microglial cells influence disease progression" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/17128093", "http://www.ncbi.nlm.nih.gov/pubmed/16228969", "http://www.ncbi.nlm.nih.gov/pubmed/8959997", "http://www.ncbi.nlm.nih.gov/pubmed/25384799" ]

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[]

[ "COX-2, ANF, estrogen receptor (ER)alpha gene, calsequestrin gene, casq2, cTnT, MCK, alpha-cardiac actin, sarco(endo)plasmic reticulum Ca2+-ATPase, SERCA, MLC-2, alpha-cardiac myosin heavy chain gene, phosphoglycerate mutase and PGAM-M are regulated by MEF-2 in the heart" ]

[ "COX-2", "ANF", "estrogen receptor (ER)alpha gene", "calsequestrin gene", "casq2", "cTnT", "MCK", "alpha-cardiac actin", "sarco(endo)plasmic reticulum Ca2+-ATPase", "SERCA", "MLC-2", "alpha-cardiac myosin heavy chain gene", "phosphoglycerate mutase", "PGAM-M", "cardiac troponin C", "cTnC" ]

[ "Inhibition of MEF2A using siRNA attenuated HB-EGF-induced COX-2, ANF expression and cell size.", "This genetic reprogramming coincides with a pronounced increase in expression of the estrogen receptor (ER)alpha gene, which we show to be a direct MEF2 target gene", "cardiac calsequestrin gene (casq2)", "Functional studies demonstrated that site-directed mutagenesis of the proximal MEF-2 and CArG box sites significantly decreased the transcription of the gene in cardiac and skeletal muscle cells, indicating that they are important to drive cardiac and skeletal muscle-specific transcription of the casq2 gene.", "DTEF-1 also interacts with MEF- 2 by coimmunoprecipitation and independently or cooperatively (with MEF-2) trans-activates the cTnT promoter", "An 85-bp region within the enhancer is highly conserved between human and mouse and contains a central AT-rich site, which is essential for enhancer activity. This site binds myocyte enhancer factor (MEF)2 factors, principally MEF2D and MEF2A in cardiocyte nuclear extracts. These results are discussed in the context of MEF2 activity and of the regulation of the alpha-cardiac actin locus.", "The cis-acting elements, MEF-2, E boxes and A/T rich elements present in the enhancer region of the mouse MCK gene are known to regulate the expression of the gene", "The sarco(endo)plasmic reticulum Ca2+-ATPases (SERCAs) belong to a family of active calcium transport enzymes encoded by the SERCA1, 2, and 3 genes. In this study, we describe the complete structure of the human SERCA2 gene and its 5 -regulatory region.", "Among the DNA cis-elements present in these two regulatory regions there are potential binding sites for: GATA-4, -5, -6, Nkx-2.5/Csx, OTF-1, USF, MEF-2, SRF, PPAR/RXR, AP-2, and TREs. Upstream from position -1.5 kb, there is no significant homology among the SERCA2 genes cloned.", "The cardiac calsequestrin gene consists of 11 exons and its 5' flanking region is characterized by the presence of a TATA-like box, muscle specific promoter elements such as 7 E-boxes, 1 MEF-2, 1 MCBF and 1 Repeat (musS) motifs, as well as several muscle non-specific transcriptional elements (AP-2A, NRE1, NRE2, p53, Spel and TFI-IIA).", "our laboratory identified a 28 bp HF-la/MEF-2 element in the MLC-2v promoter region, which confers cardiac ventricular chamber-specific gene expression during murine cardiogenesis,", "In this study, we investigated T3R alpha 1-vs. T3R beta 1-specific interactions with the myocyte enhancer-specific factor-2 (MEF-2) on the expression of the SERCA 2 gene in transient transfection assays in embryonal heart-derived H9c2 cells.", "point to T3R isoform-specific interactions with a cell type-specific transcription factor (MEF-2) in the regulation of SERCA 2 gene expression.", "In multiple independent transgenic mouse lines, we found that both a 250 base pair myosin light chain-2 ventricular promoter fragment, as well as a dimerized 28 bp sub-element (HF-1) containing binding sites for HF1a and HF1b/MEF2 factors, directed ventricular-specific reporter expression from as early as the endogenous gene, at day 7.5-8.0 post coitum.", "Myocyte-specific enhancer-binding factor (MEF-2) regulates alpha-cardiac myosin heavy chain gene expression in vitro and in vivo", "In the MLC-2 gene, an AT-rich element (HF-1b) which contains a consensus MEF-2 site is required for cardiac tissue-specific expression.", "Role of myocyte-specific enhancer-binding factor (MEF-2) in transcriptional regulation of the alpha-cardiac myosin heavy chain gene.", "In order to analyze the transcriptional regulation of the muscle-specific subunit of the human phosphoglycerate mutase (PGAM-M) gene, chimeric genes composed of the upstream region of the PGAM-M gene", "These observations define the PGAM-M enhancer as the only cardiac- and skeletal-muscle-specific enhancer characterized thus far that is mainly activated through MEF-2.", "Transcription of each gene is independently controlled but coordinately regulated. During each embryogenesis, the beta-MHC gene is expressed as part of the cardiac myogenic program under the control of NKX-2.5, MEF-2C, and GATA-4/5/6.", "We have characterized the specific DNA regulatory elements responsible for the function of the human cardiac troponin C gene (cTnC) muscle-specific enhancer in myogenic cells. We used functional transient transfection assays with deletional and site-specific mutagenesis to evaluate the role of the conserved sequence elements. Gel electrophoresis mobility shift assays (EMSA) demonstrated the ability of the functional sites to interact with nuclear proteins. We demonstrate that three distinct transcription activator binding sites commonly found in muscle-specific enhancers (a MEF-2 site, a MEF-3 site, and at least four redundant E-box sites) all contribute to full enhancer activity but a CArG box does not." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/17518763", "http://www.ncbi.nlm.nih.gov/pubmed/8035789", "http://www.ncbi.nlm.nih.gov/pubmed/17938175", "http://www.ncbi.nlm.nih.gov/pubmed/8321243", "http://www.ncbi.nlm.nih.gov/pubmed/21244855", "http://www.ncbi.nlm.nih.gov/pubmed/16049055", "http://www.ncbi.nlm.nih.gov/pubmed/8366095", "http://www.ncbi.nlm.nih.gov/pubmed/21812548", "http://www.ncbi.nlm.nih.gov/pubmed/10998641", "http://www.ncbi.nlm.nih.gov/pubmed/9043061", "http://www.ncbi.nlm.nih.gov/pubmed/15491989", "http://www.ncbi.nlm.nih.gov/pubmed/7982978", "http://www.ncbi.nlm.nih.gov/pubmed/8977381", "http://www.ncbi.nlm.nih.gov/pubmed/1532229", "http://www.ncbi.nlm.nih.gov/pubmed/19893013", "http://www.ncbi.nlm.nih.gov/pubmed/10794526", "http://www.ncbi.nlm.nih.gov/pubmed/1328854", "http://www.ncbi.nlm.nih.gov/pubmed/15040454", "http://www.ncbi.nlm.nih.gov/pubmed/8449897", "http://www.ncbi.nlm.nih.gov/pubmed/11770083", "http://www.ncbi.nlm.nih.gov/pubmed/8674419", "http://www.ncbi.nlm.nih.gov/pubmed/20075332", "http://www.ncbi.nlm.nih.gov/pubmed/12805933" ]

[]

[ "http://www.uniprot.org/uniprot/MYEF2_HUMAN", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D006321", "http://www.uniprot.org/uniprot/MYEF2_MOUSE", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005796" ]

[ "Yes, TERT mutation is associated with survival of glioma patients and was suggested as a bio-marker of gliomas." ]

[ "yes" ]

[ "Mutations lead to TERT upregulation and are associated with aggressive clinical behavior in glioblastomas.", "Kaplan-Meier's survival analysis showed that TERT promoter mutation (P=0.037), Isocitrate dehydrogenase (IDH) mutation (P<0.001), and 1p/19q codeletion (P<0.001) were associated with favorable overall survival (OS). In the subset of 116 IDH-mutated lower-grade gliomas lacking 1p/19q codeletion, 19 TERT promoter-mutated tumors exhibited longer progression-free survival (PFS) (P=0.027) and OS (P=0.004). Consistent with this observation, in the subset of 97 IDH-mutated astrocytomas, 14 TERT promoter-mutated tumors showed longer PFS (P=0.001) and OS (P=0.001). In contrast, among the subset of 74 IDH wild-type lower-grade gliomas with intact 1p/19q, TERT promoter mutation was associated with shorter PFS (P=0.001) and OS (P=0.001). Similarly, in the subset of 65 IDH wild-type astrocytomas, 16 TERT promoter-mutated tumors exhibited unfavorable PFS (P=0.007) and OS (P=0.008). Our results indicate that when combined with IDH status, TERT promoter mutation contributes to prognostic subgroups of lower-grade astrocytic tumors or 1p/19q intact lower-grade gliomas and this may further refine future molecular classification of lower-grade gliomas.", "RESULTS: TERTp-mut identified in 60.8% of gliomas (491 out of 807) was globally associated with poorer outcome (Hazard ratio (HR)=1.50). ", "TERT promoter mutations lead to high transcriptional activity under hypoxia and temozolomide treatment and predict poor prognosis in gliomas.", "Patients with TERT promoter mutations had lower survival rates, even after adjusting for other known or potential risk factors, and the incidence of mutation was correlated with patient age.", "TERT promoter mutations maintained its ability of inducing high transcriptional activity even under hypoxic and TMZ treatment conditions, and the presence of mutations was associated with poor prognosis in glioma patients. ", "Patients whose Grade III-IV gliomas exhibit TERT promoter mutations alone predominately have primary GBMs associated with poor median OS (11.5 months). Patients whose Grade III-IV gliomas exhibit IDH1/2 mutations alone predominately have astrocytic morphologies and exhibit a median OS of 57 months while patients whose tumors exhibit both TERT promoter and IDH1/2 mutations predominately exhibit oligodendroglial morphologies and exhibit median OS of 125 months.", "Patients with TERT promoter mutations had lower survival rates, even after adjusting for other known or potential risk factors, and the incidence of mutation was correlated with patient age.CONCLUSION: TERT promoter mutations were specific to gliomas. ", "We defined, based on TERTp-mut and IDH mutation status, four prognostic groups: (1) TERTp-mut and IDH-mut associated with 1p19q codeletion, overall survival (OS)>17 years; (2) TERTp-wt and IDH-mut, associated with TP53 mutation, OS=97.5 months; (3) TERTp-wt and IDH-wt, with no specific association, OS=31.6 months; (4) TERTp-mut and IDH-wt, associated with EGFR amplification, OS=15.4 months. ", "Mutations lead to TERT upregulation and are associated with aggressive clinical behavior in glioblastomas. ", "In the subset of 116 IDH-mutated lower-grade gliomas lacking 1p/19q codeletion, 19 TERT promoter-mutated tumors exhibited longer progression-free survival (PFS) (P=0.027) and OS (P=0.004). ", "The mean age at diagnosis was lowest (37 years) among patients who had gliomas with only IDH mutations and was highest (59 years) among patients who had gliomas with only TERT mutations. The molecular groups were independently associated with overall survival among patients with grade II or III gliomas but not among patients with grade IV gliomas.", "Mutations were detected in gliomas, but not in meningiomas, pituitary adenomas, cavernomas, intracranial metastases, normal brain tissues, or peripheral blood of glioma patients. Patients with TERT promoter mutations had lower survival rates, even after adjusting for other known or potential risk factors, and the incidence of mutation was correlated with patient age." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/25081751", "http://www.ncbi.nlm.nih.gov/pubmed/25314060", "http://www.ncbi.nlm.nih.gov/pubmed/24722048", "http://www.ncbi.nlm.nih.gov/pubmed/24937153", "http://www.ncbi.nlm.nih.gov/pubmed/26061753" ]

[]

[ "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=D005910" ]

[ "Tofacitinib (or CP690.550) is an oral JAK (Janus kinase) inhibitor that is approved for treatment of rheumatoid arthritis. Tofacitinib inhibits JAK family kinase members, in particular JAK1 and JAK3, achieving a broad limitation of inflammation by interfering with several cytokine receptors. Tofacitinib has also a proven efficacy as an immunosuppressive regimen after renal transplantation. \nGLPG-0634 and INCB18424 are other JAK kinase inhibitors that are being studied for treatment of rheumatoid arthritis." ]

[ "tofacitinib" ]

[ "Tofacitinib: The First Janus Kinase (JAK) inhibitor for the treatment of rheumatoid arthritis.", "Tofacitinib is the first oral Janus kinase inhibitor indicated for treatment of moderate to severe RA.", "Preclinical to clinical translation of tofacitinib, a Janus kinase inhibitor, in rheumatoid arthritis.", "The preclinical pharmacokinetic (PK)/pharmacodynamic (PD) profile of tofacitinib, an oral Janus kinase (JAK) inhibitor, in a mouse collagen-induced arthritis (mCIA) model was compared with clinical PK/PD data from patients with rheumatoid arthritis (RA).", "With tofacitinib, the first Janus kinase (JAK) inhibitor has been approved in the USA, as well as in Switzerland and other countries. ", "Tofacitinib, which is a Janus kinase (JAK) inhibitor, has shown clinical effects in the treatment of rheumatoid arthritis. ", "Tofacitinib is an oral janus kinase (JAK) inhibitor that inhibits JAK family kinase members, in particular JAK1 and JAK3, achieving a broad limitation of inflammation by interfering with several cytokine receptors. It first proved its efficacy as an immunosuppressive regimen after renal transplantation, and was recently approved by the FDA for rheumatoid arthritis. ", " In patients treated with the JAK inhibitor tofacitinib, RR for hypercholesterolaemia was 1.70 (1.10 to 2.63) that was dose related. ", "After two decades of research and development activity focussed on orally active kinase inhibitors, the first such drug (the JAK inhibitor Xeljanz, tofacitinib) was approved by the FDA in November 2012 for the treatment of rheumatoid arthritis (RA). ", "JAK inhibitor tofacitinib for treating rheumatoid arthritis: from basic to clinical.", "An orally available JAK3 inhibitor, tofacitinib, has been applied for RA, with satisfactory effects and acceptable safety in multiple clinical examinations. ", "Subsequently, multiple phase 3 studies were carried out, and tofacitinib with or without methotrexate (MTX) is efficacious and has a manageable safety profile in active RA patients who are MTX naïve or show inadequate response to methotrexate (MTX-IR), disease-modifying antirheumatic drugs (DMARD)-IR, or tumor necrosis factor (TNF)-inhibitor-IR.", "Taken together, an orally available kinase inhibitor tofacitinib targeting JAK-mediated signals would be expected to be a new option for RA treatment.", "A non-selective JAK inhibitor, ruxolitinib, has recently been approved to treat myelofibrosis whereas tofacitinib is poised for approval to treat rheumatoid arthritis. ", "The recent disclosure of the clinical efficacy of a selective JAK1 inhibitor (GLPG-0634) in rheumatoid arthritis and detailed disclosure of the some potent and highly selective JAK1 inhibitors provide a clear stimulus for further activity in this area. ", "These results suggest that the JAK inhibitor tofacitinib suppresses osteoclast-mediated structural damage to arthritic joints, and this effect is secondary to decreased RANKL production.", "More recently, the Janus kinase (JAK) inhibitor tofacitinib has been evaluated as a potential new treatment option in RA and is awaiting approval.", "A total of 140 patients were randomised to tofacitinib 1, 3, 5, 10 mg or placebo twice daily and the American College of Rheumatology 20% improvement criteria (ACR20) response rate at week 12, a primary end point, was significant for all tofacitinib treatment groups. Thus, an orally available tofacitinib in combination with MTX was efficacious and had a manageable safety profile. Tofacitinib at 5 and 10 mg twice a day appears suitable for further evaluation to optimise the treatment of RA.", "Moreover, induction of IL-10 production by DCs can be one mechanism of action of the JAK inhibitor (tofacitinib) which have shown high efficiency on active rheumatoid arthritis in clinical trials.", "Recently, CP-690,550 (tofacitinib), originally developed as a JAK3 inhibitor, has been shown to be effective in phase III clinical trials of rheumatoid arthritis and collagen-induced arthritis (CIA) models, but the precise mechanism of the effect, especially with respect to Th17 cells, is poorly understood. ", " Tofacitinib (CP-690,550) is a novel JAK inhibitor that is currently in clinical trials for the treatment of rheumatoid arthritis (RA). ", "To compare the efficacy, safety, and tolerability of 6 dosages of oral tofacitinib (CP-690,550) with placebo for the treatment of active rheumatoid arthritis (RA) in patients receiving a stable background regimen of methotrexate (MTX) who have an inadequate response to MTX monotherapy. ", "In patients with active RA in whom the response to MTX has been inadequate, the addition of tofacitinib at a dosage ≥3 mg twice daily showed sustained efficacy and a manageable safety profile over 24 weeks.", "OBJECTIVE: To compare the efficacy, safety, and tolerability of 5 doses of oral tofacitinib (CP-690,550) or adalimumab monotherapy with placebo for the treatment of active rheumatoid arthritis (RA) in patients with an inadequate response to disease-modifying antirheumatic drugs.", "Tofacitinib monotherapy at ≥3 mg twice a day was efficacious in the treatment of patients with active RA over 24 weeks and demonstrated a manageable safety profile.", "The new JAK3 inhibitor, CP690,550, has shown efficacy in the treatment of rheumatoid arthritis.", "CP-690,550 is a potent and selective JAK inhibitor currently in clinical trials for rheumatoid arthritis (RA) and other autoimmune disease indications.", "Co-administration of the JAK inhibitor CP-690,550 and methotrexate is well tolerated in patients with rheumatoid arthritis without need for dose adjustment.", "To investigate the effects of methotrexate (MTX) on the pharmacokinetics (PK) of CP-690,550, a novel Janus kinase (JAK) inhibitor in development as a therapy for rheumatoid arthritis (RA), to determine the effects of multiple doses of CP-690,550 on the PK of MTX, and to evaluate the short-term safety and tolerability of co-administration of CP-690,550 and MTX. ", "Improved pain, physical functioning and health status in patients with rheumatoid arthritis treated with CP-690,550, an orally active Janus kinase (JAK) inhibitor: results from a randomised, double-blind, placebo-controlled trial.", "CP-690,550 was efficacious in improving the pain, function and health status of patients with RA, from week 1 to week 6.", "Our findings indicate that CP-690,550 is efficacious in the treatment of RA, resulting in rapid, statistically significant, and clinically meaningful reductions in the signs and symptoms of RA.", "INCB18424 targeting Jak1/2 and CP690,550 targeting Jak3 has been developed and is now on phase II clinical study for RA." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/19587388", "http://www.ncbi.nlm.nih.gov/pubmed/20732649", "http://www.ncbi.nlm.nih.gov/pubmed/22374445", "http://www.ncbi.nlm.nih.gov/pubmed/24013646", "http://www.ncbi.nlm.nih.gov/pubmed/19565475", "http://www.ncbi.nlm.nih.gov/pubmed/22777068", "http://www.ncbi.nlm.nih.gov/pubmed/23599436", "http://www.ncbi.nlm.nih.gov/pubmed/23212593", "http://www.ncbi.nlm.nih.gov/pubmed/23961674", "http://www.ncbi.nlm.nih.gov/pubmed/24285764", "http://www.ncbi.nlm.nih.gov/pubmed/19404006", "http://www.ncbi.nlm.nih.gov/pubmed/22121136", "http://www.ncbi.nlm.nih.gov/pubmed/20701804", "http://www.ncbi.nlm.nih.gov/pubmed/22006202", "http://www.ncbi.nlm.nih.gov/pubmed/24193189", "http://www.ncbi.nlm.nih.gov/pubmed/22209716", "http://www.ncbi.nlm.nih.gov/pubmed/22147632", "http://www.ncbi.nlm.nih.gov/pubmed/23523202", "http://www.ncbi.nlm.nih.gov/pubmed/22252297", "http://www.ncbi.nlm.nih.gov/pubmed/20233177", "http://www.ncbi.nlm.nih.gov/pubmed/23384668", "http://www.ncbi.nlm.nih.gov/pubmed/22971156", "http://www.ncbi.nlm.nih.gov/pubmed/24218541", "http://www.ncbi.nlm.nih.gov/pubmed/23642011", "http://www.ncbi.nlm.nih.gov/pubmed/21884580", "http://www.ncbi.nlm.nih.gov/pubmed/21105711", "http://www.ncbi.nlm.nih.gov/pubmed/22460142", "http://www.ncbi.nlm.nih.gov/pubmed/23627915", "http://www.ncbi.nlm.nih.gov/pubmed/22899318", "http://www.ncbi.nlm.nih.gov/pubmed/21548952", "http://www.ncbi.nlm.nih.gov/pubmed/21952978" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001172", "http://www.uniprot.org/uniprot/JAK2_PIG", "http://www.uniprot.org/uniprot/JAK2_MOUSE", "http://www.uniprot.org/uniprot/JAK2_RAT", "http://www.uniprot.org/uniprot/JAK2_HUMAN", "http://www.uniprot.org/uniprot/JAK3_HUMAN", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0004713", "http://www.uniprot.org/uniprot/JAK3_MOUSE", "http://www.uniprot.org/uniprot/JAK1_MOUSE", "http://www.uniprot.org/uniprot/JAK3_RAT", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D053614", "http://www.uniprot.org/uniprot/JAK2_PONAB", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D053613", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D053612", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0033673", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013812", "http://www.uniprot.org/uniprot/JAK1_DANRE", "http://www.disease-ontology.org/api/metadata/DOID:7148", "http://www.uniprot.org/uniprot/JAK1_CYPCA", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D053616", "http://www.uniprot.org/uniprot/JAK2_CHICK", "http://www.uniprot.org/uniprot/JAK1_HUMAN" ]

[ "Translation from a DMD exon 5 IRES results in a functional dystrophin isoform that attenuates dystrophinopathy in humans and mice", "Alternative translation initiation beginning in DMD exon 6 with the use of an internal ribosome entry site (IRES) within exon 5 that is glucocorticoid inducible leads to expression of a highly functional N-truncated dystrophin isoform which is able to ameliorate disease severity.", "Translation from a DMD exon 5 IRES results in a functional dystrophin isoform that attenuates dystrophinopathy in humans and mice " ]

[]

[ "Translation from a DMD exon 5 IRES results in a functional dystrophin isoform that attenuates dystrophinopathy in humans and mice", "amelioration of disease severity has been shown to result from alternative translation initiation beginning in DMD exon 6 that leads to expression of a highly functional N-truncated dystrophin. Here we demonstrate that this isoform results from usage of an internal ribosome entry site (IRES) within exon 5 that is glucocorticoid inducible", "However, amelioration of disease severity has been shown to result from alternative translation initiation beginning in DMD exon 6 that leads to expression of a highly functional N-truncated dystrophin.", "Translation from a DMD exon 5 IRES results in a functional dystrophin isoform that attenuates dystrophinopathy in humans and mice.", "We generated a truncated reading frame upstream of the IRES by exon skipping, which led to synthesis of a functional N-truncated isoform in both human subject-derived cell lines and in a new DMD mouse model, where expression of the truncated isoform protected muscle from contraction-induced injury and corrected muscle force to the same level as that observed in control mice.", "However, amelioration of disease severity has been shown to result from alternative translation initiation beginning in DMD exon 6 that leads to expression of a highly functional N-truncated dystrophin", "We generated a truncated reading frame upstream of the IRES by exon skipping, which led to synthesis of a functional N-truncated isoform in both human subject-derived cell lines and in a new DMD mouse model, where expression of the truncated isoform protected muscle from contraction-induced injury and corrected muscle force to the same level as that observed in control mice", "However, amelioration of disease severity has been shown to result from alternative translation initiation beginning in DMD exon 6 that leads to expression of a highly functional N-truncated dystrophin. ", "We generated a truncated reading frame upstream of the IRES by exon skipping, which led to synthesis of a functional N-truncated isoform in both human subject-derived cell lines and in a new DMD mouse model, where expression of the truncated isoform protected muscle from contraction-induced injury and corrected muscle force to the same level as that observed in control mice. ", "However, amelioration of disease severity has been shown to result from alternative translation initiation beginning in DMD exon 6 that leads to expression of a highly functional N-truncated dystrophin.", "We generated a truncated reading frame upstream of the IRES by exon skipping, which led to synthesis of a functional N-truncated isoform in both human subject-derived cell lines and in a new DMD mouse model, where expression of the truncated isoform protected muscle from contraction-induced injury and corrected muscle force to the same level as that observed in control mice.", "amelioration of disease severity has been shown to result from alternative translation initiation beginning in DMD exon 6 that leads to expression of a highly functional N-truncated dystrophin.", "However, amelioration of disease severity has been shown to result from alternative translation initiation beginning in DMD exon 6 that leads to expression of a highly functional N-truncated dystrophin.", "Translation from a DMD exon 5 IRES results in a functional dystrophin isoform that attenuates dystrophinopathy in humans and mice." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/25108525" ]

[]

[]

[ "Thalassemia is genetic diseases of the blood caused by mutations in the globin gene. Main goal for thalassemia treatment is to develop homologous recombination based gene therapy in order to cure these diseases. Zinc finger nucleases (ZFNs) and TAL effector nucleases (TALENs) are proper targets for the human globin gene. Genome editing using engineered nucleases such as ZFNs and TALENs has become a powerful technology for reverse genetics.", "The newly identified DNA nucleases that can be used to treat thalassemia are the transcription activator-like effector nucleases (TALEN). These are engineered proteins able to stimulate targeted integration of therapeutic wild-type beta-globin cDNAs to the endogenous beta-globin locus." ]

[ "TALEN", "Transcription activator-like effector nucleases", "Crispr/CAS", "zinc-finger nucleases" ]

[ "Transcription activator-like effector nuclease (TALEN) and zinc finger nuclease (ZFN) DNA editing technology enables site-directed engineering of the genome", "We used this opportunity to evaluate the effect of total donor homology on transcription activator-like effector nuclease (TALEN) mediated bi-allelic modification. ", "Herein we describe our applications of site-specific nucleases, especially transcription activator-like effector nucleases, to engineer specific alterations in the genomes of pigs and cows.", "In this study, we used zinc finger nuclease-mediated knockout of the aryl hydrocarbon receptor (AHR) or AHR nuclear translocator (ARNT) in MCF7 and AHR knockout in MDA-MB-231 human breast cancer cells to investigate cross talk among AHR, ARNT, and estrogen receptor α (ERα).", " For example, after binding DNA, TALEs fused to transcriptional activation domains can function as robust transcription factors (TALE-TFs), while fused to restriction endonucleases (TALENs) can cut DNA. ", "Genome editing using engineered nucleases such as transcription activator-like effector nucleases (TALENs) has become a powerful technology for reverse genetics", "Here, we describe a robust process combining efficient generation of integration-free β-Thal iPSCs from the cells of patients and transcription activator-like effector nuclease (TALEN)-based universal correction of HBB mutations in situ.", "We report here the correction of α-thalassemia major hydrops fetalis in transgene-free iPS cells using zinc finger-mediated insertion of a globin transgene in the AAVS1 site on human chromosome 19. ", " Here, we review the development of Cas9 as an important tool to not only edit the genomes of a number of different prokaryotic and eukaryotic species, but also as an efficient system for site-specific transcriptional repression or activation. Additionally, a specific Cas9 protein has been observed to target an RNA substrate, suggesting that Cas9 may have the ability to be programmed to target RNA as well.", "RNA-guided endonucleases (RGENs), derived from the prokaryotic adaptive immune system known as CRISPR/Cas, enable targeted genome engineering in cells and organisms. ", "The CRISPR/Cas technology has been successfully used to stimulate the integration of small DNA sequences in a target locus to produce gene mutations." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/24305179", "http://www.ncbi.nlm.nih.gov/pubmed/24286287", "http://www.ncbi.nlm.nih.gov/pubmed/24323919", "http://www.ncbi.nlm.nih.gov/pubmed/24305403", "http://www.ncbi.nlm.nih.gov/pubmed/24299737", "http://www.ncbi.nlm.nih.gov/pubmed/24211574", "http://www.ncbi.nlm.nih.gov/pubmed/24155235", "http://www.ncbi.nlm.nih.gov/pubmed/24305278", "http://www.ncbi.nlm.nih.gov/pubmed/24291598", "http://www.ncbi.nlm.nih.gov/pubmed/24253446", "http://www.ncbi.nlm.nih.gov/pubmed/23408852", "http://www.ncbi.nlm.nih.gov/pubmed/21953455", "http://www.ncbi.nlm.nih.gov/pubmed/23002118", "http://www.ncbi.nlm.nih.gov/pubmed/24157834", "http://www.ncbi.nlm.nih.gov/pubmed/23386979" ]

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[ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001483", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0004523", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0008821", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0032075", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004269", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013789", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D015723", "http://www.disease-ontology.org/api/metadata/DOID:1099", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004260", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004247", "http://www.uniprot.org/uniprot/NUCE_STRPN", "http://www.uniprot.org/uniprot/NUCA_BACSU", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D064112", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D064113", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D064130", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D017085", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D017086", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0004530", "http://www.uniprot.org/uniprot/NUCE_STRR6", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D059372", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004274", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0004518", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0032074", "http://www.uniprot.org/uniprot/NUC1_SYNRA", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0032069", "http://www.uniprot.org/uniprot/NUCA_NOSS1", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D003851", "http://www.disease-ontology.org/api/metadata/DOID:10241", "http://www.disease-ontology.org/api/metadata/DOID:12241", "http://www.uniprot.org/uniprot/NUCA_SERMA" ]

[ "Yes, ziconotide/omega-conotoxin MVIIA blocks N-type calcium channels." ]

[ "yes" ]

[ "Since this region partially overlaps with residues previously implicated in block of the channel by omega-conotoxin GVIA, we assessed the effects of mutations in the putative EF hand domain on channel block by omega-conotoxin GVIA and the structurally related omega-conotoxin MVIIA. Both of the toxins irreversibly block the activity of wild type alpha(1B) N-type channels. ", "Despite their high sequence homology, the peptide neurotoxins omega-conotoxin MVIIA and MVIIC selectively block N- and P/Q-type calcium channels, respectively. ", " Binding assay for both N- and P/Q-type calcium channels showed that amino acid residues restricted to the N-terminal half are important for the recognition of N-type channels, whereas essential residues for P/Q-type channel recognition are widely spread over the whole omega-conotoxin molecule.", "Ziconotide is a novel peptide that blocks the entry of calcium into neuronal N-type voltage-sensitive calcium channels, preventing the conduction of nerve signals.", "Ziconotide is a selective, potent and reversible blocker of neuronal N-type voltage-sensitive calcium channels (VSCCs).", "The therapeutic benefit of ziconotide derives from its potent and selective blockade of neuronal N-type voltage-sensitive calcium channels.", "Interactions of intrathecally administered ziconotide, a selective blocker of neuronal N-type voltage-sensitive calcium channels, with morphine on nociception in rats.", "Ziconotide, a new N-type calcium channel blocker, administered intrathecally for acute postoperative pain.", "Ziconotide, an intrathecally administered N-type calcium channel antagonist for the treatment of chronic pain.", "Thus, ziconotide is the first of a new class of agents--N-type calcium channel blockers, or NCCBs.", "Ziconotide, formerly known also as SNX- 111, represents a new class of agents, the N-type calcium channel blockers.", "The selective N-type calcium channel blocker ziconotide ameliorates severe chronic pain but has a narrow therapeutic window and requires intrathecal administration.", "A selective N-type calcium channel inhibitor, ziconotide (Prialt), is a neuroactive peptide recently marketed as a novel nonopioid treatment for severe chronic pain.", "As the clinically available analgesics, pregabalin (alpha2delta-subunit calcium channel ligand), ziconotide (N-type calcium channel blocker), mexiletine (sodium channel blocker), and duloxetine (serotonin and norepinephrine reuptake inhibitors) were evaluated in these neurochemically-induced allodynia models.", "The present investigation was designed to assess the safety and analgesic efficacy of ziconotide, a new N-type calcium channel blocker, when administered intrathecally to patients with acute postoperative pain.", "Inhibition of the N-type calcium channel by intrathecal administration of the channel-specific blocker omega-conotoxin MVIIA (ziconotide) is efficacious in the treatment of severe chronic pain.", "Ziconotide is a powerful analgesic drug that has a unique mechanism of action involving potent and selective block of N-type calcium channels, which control neurotransmission at many synapses.", "In conclusion, present findings provide implication that the spinal anti-nociceptive mechanistic site of pregabalin is different from that of ziconotide, mexiletine, and duloxetine, and pregabalin could have a broader anti-nociceptive mechanism other than N-type calcium channel blockade.", "Ziconotide (SNX-111), a selective blocker of neuronal N-type voltage-sensitive calcium channels, is antinociceptive when it is administered intrathecally.", "Effects of intrathecal administration of ziconotide, a selective neuronal N-type calcium channel blocker, on mechanical allodynia and heat hyperalgesia in a rat model of postoperative pain.", "A state-dependent Ca(V)2.2 inhibitor may provide an improved therapeutic window over ziconotide, the peptidyl Ca(V)2.2 inhibitor used clinically. ", "There is also human validation data from ziconotide, the CaV2.2-selective peptidyl inhibitor used clinically to treat refractory pain. ", "A selective N-type calcium channel inhibitor, ziconotide (Prialt), is a neuroactive peptide recently marketed as a novel nonopioid treatment for severe chronic pain. ", "The neuroprotective effects of intrathecal administration of the selective N-type calcium channel blocker ziconotide in a rat model of spinal ischemia." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/11279062", "http://www.ncbi.nlm.nih.gov/pubmed/16831862", "http://www.ncbi.nlm.nih.gov/pubmed/16225359", "http://www.ncbi.nlm.nih.gov/pubmed/22608964", "http://www.ncbi.nlm.nih.gov/pubmed/20413151", "http://www.ncbi.nlm.nih.gov/pubmed/25456079", "http://www.ncbi.nlm.nih.gov/pubmed/10666532", "http://www.ncbi.nlm.nih.gov/pubmed/15578997", "http://www.ncbi.nlm.nih.gov/pubmed/16207099", "http://www.ncbi.nlm.nih.gov/pubmed/10834782", "http://www.ncbi.nlm.nih.gov/pubmed/20188724", "http://www.ncbi.nlm.nih.gov/pubmed/22084632", "http://www.ncbi.nlm.nih.gov/pubmed/17063978", "http://www.ncbi.nlm.nih.gov/pubmed/16845440", "http://www.ncbi.nlm.nih.gov/pubmed/11059665", "http://www.ncbi.nlm.nih.gov/pubmed/21577088", "http://www.ncbi.nlm.nih.gov/pubmed/10666519", "http://www.ncbi.nlm.nih.gov/pubmed/15209164", "http://www.ncbi.nlm.nih.gov/pubmed/9315745", "http://www.ncbi.nlm.nih.gov/pubmed/25446431", "http://www.ncbi.nlm.nih.gov/pubmed/22428804", "http://www.ncbi.nlm.nih.gov/pubmed/17199507", "http://www.ncbi.nlm.nih.gov/pubmed/10436454", "http://www.ncbi.nlm.nih.gov/pubmed/22188924", "http://www.ncbi.nlm.nih.gov/pubmed/21992243", "http://www.ncbi.nlm.nih.gov/pubmed/19300539", "http://www.ncbi.nlm.nih.gov/pubmed/10547097" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D020864" ]

[ "OCT3 plays a role in serotonin clearance" ]

[ "serotonin clearance" ]

[ "The organic cation transporter 3 (OCT3) is a widely expressed transporter for endogenous and exogenous organic cations. Of particular interest is OCT3 expression and function in the brain, where it plays a role in serotonin clearance and influences mood and behavior. ", "Interestingly, OCT3 mRNA is however also significantly up-regulated in the hippocampus of serotonin transporter knockout mice where it might serve as an alternative reuptake mechanism for serotonin.", "Of particular interest is OCT3 expression and function in the brain, where it plays a role in serotonin clearance and influences mood and behavior.", "However, OCT3 was determined to be a high-capacity and low-affinity transporter for the neurotransmitters dopamine (DA), norepinephrine (NE), and serotonin (5-HT).", "Organic cation transporter 3 (OCT3) is a high-capacity, low-affinity transporter that mediates bidirectional, sodium-independent transport of dopamine, norepinephrine, epinephrine, serotonin, and histamine.", "The effect of blockade of either 5-hydroxytryptamine (5-HT)/serotonin transporter (SERT) with citalopram or the organic cation transporter 3 (OCT3)/plasma membrane monoamine transporter (PMAT) with decynium-22 (D-22) on spontaneous and evoked release of 5-HT in the nucleus tractus solitarius (NTS) was investigated in rat brainstem slices treated with gabazine", "Of particular interest is OCT3 expression and function in the brain, where it plays a role in serotonin clearance and influences mood and behavior", "However, OCT3 was determined to be a high-capacity and low-affinity transporter for the neurotransmitters dopamine (DA), norepinephrine (NE), and serotonin (5-HT)", "Interestingly, OCT3 mRNA is however also significantly up-regulated in the hippocampus of serotonin transporter knockout mice where it might serve as an alternative reuptake mechanism for serotonin", "Organic cation transporter 3 (OCT3) is a high-capacity, low-affinity transporter that mediates bidirectional, sodium-independent transport of dopamine, norepinephrine, epinephrine, serotonin, and histamine", "RESULTS: We found a drastic decrease in IL-4 production by stimulated basophils on exposure to serotonin (5-hydroxytryptamine [5-HT]) that is taken up by basophils through the specific high-affinity transporters serotonin transporter and the polyspecific, high-capacity organic cation transporter 3 (OCT3; or Slc22a3) but inhibits their function exclusively through the latter. ", "Of particular interest is OCT3 expression and function in the brain, where it plays a role in serotonin clearance and influences mood and behavior. ", "However, OCT3 was determined to be a high-capacity and low-affinity transporter for the neurotransmitters dopamine (DA), norepinephrine (NE), and serotonin (5-HT). ", "Organic cation transporter 3: Keeping the brake on extracellular serotonin in serotonin-transporter-deficient mice.", "Organic cation transporter capable of transporting serotonin is up-regulated in serotonin transporter-deficient mice.", "Interestingly, OCT3 mRNA is however also significantly up-regulated in the hippocampus of serotonin transporter knockout mice where it might serve as an alternative reuptake mechanism for serotonin.", "Of particular interest is OCT3 expression and function in the brain, where it plays a role in serotonin clearance and influences mood and behavior.", "However, OCT3 was determined to be a high-capacity and low-affinity transporter for the neurotransmitters dopamine (DA), norepinephrine (NE), and serotonin (5-HT).", "We found a drastic decrease in IL-4 production by stimulated basophils on exposure to serotonin (5-hydroxytryptamine [5-HT]) that is taken up by basophils through the specific high-affinity transporters serotonin transporter and the polyspecific, high-capacity organic cation transporter 3 (OCT3; or Slc22a3) but inhibits their function exclusively through the latter." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/20402963", "http://www.ncbi.nlm.nih.gov/pubmed/19033200", "http://www.ncbi.nlm.nih.gov/pubmed/19280114", "http://www.ncbi.nlm.nih.gov/pubmed/19025979", "http://www.ncbi.nlm.nih.gov/pubmed/21636115", "http://www.ncbi.nlm.nih.gov/pubmed/24618127", "http://www.ncbi.nlm.nih.gov/pubmed/24246570", "http://www.ncbi.nlm.nih.gov/pubmed/23982114", "http://www.ncbi.nlm.nih.gov/pubmed/12584728", "http://www.ncbi.nlm.nih.gov/pubmed/19371745" ]

[]

[ "http://www.biosemantics.org/jochem#4274509", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012701", "http://www.biosemantics.org/jochem#http://www.biosemantics.org/jochem#:4274509", "http://www.uniprot.org/uniprot/OCT3_ARATH" ]

[ "Fanconi anemia is a rare genetic disorder associated with an increased risk of leukemias and solid tumors." ]

[]

[ "Fanconi anemia (FA) is a rare autosomal recessive disease characterized by a greatly increased risk of cancer among those diagnosed with the syndrome", "Fanconi anaemia (FA) is an inherited condition characterised by congenital and developmental abnormalities and a strong cancer predisposition", "Fanconi anemia (FA) is a heterogeneous disease characterized by spontaneous chromosomal breaks and abnormal DNA repair. Major clinical problems in FA include congenital abnormalities, endocrinopathies, early onset bone marrow failure and increased risk of myelodysplastic syndrome, acute leukemia and solid tumors", "Fanconi anemia is associated with an increased risk of malignancy. ", "Fanconi anemia (FA) is a rare genetic disorder characterized by bone marrow failure, congenital abnormalities, and an increased risk for cancer and leukemia", "Fanconi anemia (FA) is an autosomal recessive, cancer susceptibility disorder characterized by diverse clinical features, such as short stature, skeletal or skin abnormalities, progressive bone marrow (BM) failure, and increased risk of malignancies", "The FA patients have a high risk of developing malignancies", "Fanconi anemia (FA) is an autosomal recessive DNA repair disorder with affected individuals having a high risk of developing acute myeloid leukaemia and certain solid tumours.", "In summary, both heterozygous and homozygous mutations in several Fanconi anemia-predisposing genes are associated with an increased risk of ESCC in Iran.", "Fanconi anemia (FA) is an inherited disease characterized by bone marrow failure, increased cancer risk and hypersensitivity to DNA cross-linking agents, implying a role for this pathway in the maintenance of genomic stability.", "BACKGROUND: Fanconi anemia (FA) is a rare autosomal recessive genetic disorder characterized by bone marrow failure and increased risk of cancers including acute myelogenous leukemia and various solid tumors, especially head and neck cancer.", "Fanconi anemia (FA) is a rare recessive DNA repair disorder that is clinically characterized by congenital malformations, progressive bone marrow failure, and increased incidence of malignancies, especially acute myeloid leukemia and squamous cell carcinomas of the head and neck (HNSCCs) and the anogenital regions.", "In summary, both heterozygous and homozygous mutations in several Fanconi anemia-predisposing genes are associated with an increased risk of ESCC in Iran.", "FA is one of a group of recessive syndromes characterized by excessive spontaneous chromosomal breakage in which heterozygote carriers appear to display an increased risk of cancer and there is some indirect evidence that FA carriers may also be at increased risk of AML.", "Mutations in Fanconi anemia genes and the risk of esophageal cancer.", "The co-occurrence of brain tumors, Fanconi anemia, and breast cancer observed in one of these kindreds constitutes a new syndromic association.", "Fanconi anemia is a genetically heterogeneous disorder associated with chromosome instability and a highly elevated risk for developing cancer.", "BRCA2 is an FA gene and additionally conveys an inherited risk for breast, ovarian, and pancreatic cancer for individuals carrying a single mutated allele [N. G. Howlett et al., Science (Wash. DC), 297: 606-609, 2002]", "Around 10-15% of individuals with recessively inherited Fanconi anaemia (FA) develop AML.", "The co-occurrence of brain tumors, Fanconi anemia, and breast cancer observed in one of these kindreds constitutes a new syndromic association", "It is postulated that both T and B cells could be involved in the development of leukemia in Fanconi's anemia patients, assuming that chromosome breaks constitute a factor predisposing to the development of malignancy.", "Patients with Fanconi Anemia (FANC) have a well documented increased risk to develop malignancies, especially Acute Myeloid Leukemia (AML) and Myelodysplastic Syndrome (MDS)", "The findings within this family support the hypothesis of an increased risk to develop malignancies in heterozygous carriers of FANC-mutations", "FA is one of a group of recessive syndromes characterized by excessive spontaneous chromosomal breakage in which heterozygote carriers appear to display an increased risk of cancer and there is some indirect evidence that FA carriers may also be at increased risk of AML", "Fanconi anemia (FA) is a rare autosomal recessive disease characterized by skeletal defects, anemia, chromosomal instability and increased risk of leukemia" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/22965917", "http://www.ncbi.nlm.nih.gov/pubmed/24259538", "http://www.ncbi.nlm.nih.gov/pubmed/1084238", "http://www.ncbi.nlm.nih.gov/pubmed/10994546", "http://www.ncbi.nlm.nih.gov/pubmed/21279724", "http://www.ncbi.nlm.nih.gov/pubmed/21355096", "http://www.ncbi.nlm.nih.gov/pubmed/22504776", "http://www.ncbi.nlm.nih.gov/pubmed/21131752", "http://www.ncbi.nlm.nih.gov/pubmed/21109493", "http://www.ncbi.nlm.nih.gov/pubmed/17909071", "http://www.ncbi.nlm.nih.gov/pubmed/18786261", "http://www.ncbi.nlm.nih.gov/pubmed/12750283", "http://www.ncbi.nlm.nih.gov/pubmed/22937327", "http://www.ncbi.nlm.nih.gov/pubmed/12354784", "http://www.ncbi.nlm.nih.gov/pubmed/19728769", "http://www.ncbi.nlm.nih.gov/pubmed/14559878", "http://www.ncbi.nlm.nih.gov/pubmed/12685843", "http://www.ncbi.nlm.nih.gov/pubmed/23146055" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D051856", "http://www.disease-ontology.org/api/metadata/DOID:13636", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005199", "http://www.disease-ontology.org/api/metadata/DOID:1062" ]

[ "In 1999, proof-of-concept for treating these disorders was obtained in a mouse model of muscular dystrophy, when administration of aminoglycosides restored protein translation by inducing the ribosome to bypass a PTC.\nAminoglycosides can bypass nonsense mutations and are the prototypic agents for translational bypass therapy (TBT).\nExpression of retroviral replication enzymes (Pol) requires a controlled translational recoding event to bypass the stop codon at the end of gag. This recoding event occurs either by direct suppression of termination via the insertion of an amino acid at the stop codon (readthrough) or by alteration of the mRNA reading frame (frameshift).", "Yes it is. The UGA stop codon was found to code for seleno-cysteine in a number of Saccharomyces cerevisiae genes, whereas the UAG stop codon was shown to code for pyrro-lysine in some archaean species. Moreover, in experimental and therapeutic settings, aminoglycoside-induced stop codon bypass has been used to restore protein translation by promoting readthrough of stop codons, generated by mutations causing premature termination of protein synthesis. Additionally, cytosine deamination to uracil in stop codons may result in stop codon bypass, whereas in a number of polycistronic genes or sequential ORFs, there is evidence for stop codon bypass, although their induction mechanisms are still unclear. Additional hypotheses for stop codon bypass involve the 3' context of the translated transcript, non-conventional anticodon-codon interactions or translational frameshifts." ]

[ "yes" ]

[ "In 1999, proof-of-concept for treating these disorders was obtained in a mouse model of muscular dystrophy, when administration of aminoglycosides restored protein translation by inducing the ribosome to bypass a PTC.", "Aminoglycosides can bypass nonsense mutations and are the prototypic agents for translational bypass therapy (TBT).", "Expression of retroviral replication enzymes (Pol) requires a controlled translational recoding event to bypass the stop codon at the end of gag. This recoding event occurs either by direct suppression of termination via the insertion of an amino acid at the stop codon (readthrough) or by alteration of the mRNA reading frame (frameshift).", "Recent studies on translation termination in the yeast Saccharomyces cerevisiae have not only enabled the identification of the key components of the termination machinery, but have also revealed several regulatory mechanisms that might enable the controlled synthesis of C-terminally extended polypeptides via stop-codon readthrough. ", "The effects of all possible single-base mutations in the codons flanking the stop indicated that 3' contexts of the form CAR-YYA confer leakiness and that the 3' context permits read through of UAA and UGA stop codons as well as UAG.", "As a first step to elucidate the mechanism(s) by which ribosomes bypass leaky stop codons in vivo, we have devised a system in which readthrough is coupled to the transient expression of beta-glucuronidase (GUS) in tobacco protoplasts. " ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/17961216", "http://www.ncbi.nlm.nih.gov/pubmed/2010914", "http://www.ncbi.nlm.nih.gov/pubmed/21969101", "http://www.ncbi.nlm.nih.gov/pubmed/18809619", "http://www.ncbi.nlm.nih.gov/pubmed/23083810", "http://www.ncbi.nlm.nih.gov/pubmed/17187982", "http://www.ncbi.nlm.nih.gov/pubmed/2207158", "http://www.ncbi.nlm.nih.gov/pubmed/17881586", "http://www.ncbi.nlm.nih.gov/pubmed/11492998", "http://www.ncbi.nlm.nih.gov/pubmed/7479046", "http://www.ncbi.nlm.nih.gov/pubmed/23649834", "http://www.ncbi.nlm.nih.gov/pubmed/9223347", "http://www.ncbi.nlm.nih.gov/pubmed/9537381", "http://www.ncbi.nlm.nih.gov/pubmed/22718819", "http://www.ncbi.nlm.nih.gov/pubmed/2103444", "http://www.ncbi.nlm.nih.gov/pubmed/10102819", "http://www.ncbi.nlm.nih.gov/pubmed/17158156", "http://www.ncbi.nlm.nih.gov/pubmed/12711673", "http://www.ncbi.nlm.nih.gov/pubmed/2691247" ]

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[ "http://www.uniprot.org/uniprot/BSC1_YEAST", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D018387", "http://www.uniprot.org/uniprot/BSC2_YEAST", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D018388", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D018389", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D003062", "http://www.uniprot.org/uniprot/BSC5_YEAST", "http://www.uniprot.org/uniprot/BSC4_YEAST", "http://www.uniprot.org/uniprot/BSC6_YEAST" ]

[ "Yes, the β1-integrin is recycled." ]

[ "yes" ]

[ "Pathways selectively regulating β1-integrin recycling are implicated in cancer invasion and metastasis,", "integrin-positive early and recycling endosomes ", "LPA-induced recycling of β1 integrin,", "RCP-mediated recycling of α5β1 integrin ", "CycD1 overexpression increased β1 integrin recycling ", "inhibition of autophagy slowed down the lysosomal degradation of internalized β1 integrins and promoted its membrane recycling", "recycling pathway for β1-integrin", " β1 integrin recycling", " β1 integrin recycling", " controlling β1 integrin recycling to the plasma membrane ", "integrin recycling pathway", "Distinct recycling of active and inactive β1 integrins.", "Integrin functions are controlled by regulating their affinity for ligand, and by the efficient recycling of intact integrins through endosomes.", " β1 integrins, resulting in their recycling to the cell surface where they can be reused." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/23264734", "http://www.ncbi.nlm.nih.gov/pubmed/22454518", "http://www.ncbi.nlm.nih.gov/pubmed/24036548", "http://www.ncbi.nlm.nih.gov/pubmed/24887021", "http://www.ncbi.nlm.nih.gov/pubmed/25344254", "http://www.ncbi.nlm.nih.gov/pubmed/26256210", "http://www.ncbi.nlm.nih.gov/pubmed/23839032", "http://www.ncbi.nlm.nih.gov/pubmed/23139422", "http://www.ncbi.nlm.nih.gov/pubmed/24719112", "http://www.ncbi.nlm.nih.gov/pubmed/22561348", "http://www.ncbi.nlm.nih.gov/pubmed/22222055" ]

[]

[]

[ "In 3 families with Bardet-Biedl syndrome (BBS) and Hirschsprung disease (HSCR), concomitant mutations in BBS genes and regulatory RET elements have been identified. Analysis of the data suggests that BBS mutations can potentiate HSCR predisposing RET alleles, which by themselves are insufficient to cause disease." ]

[ "yes" ]

[ "Epistasis between RET and BBS mutations modulates enteric innervation and causes syndromic Hirschsprung disease", "Here, we report 3 families with BBS and HSCR with concomitant mutations in BBS genes and regulatory RET elements, whose functionality is tested in physiologically relevant assays. Our data suggest that BBS mutations can potentiate HSCR predisposing RET alleles, which by themselves are insufficient to cause disease", "Epistasis between RET and BBS mutations modulates enteric innervation and causes syndromic Hirschsprung disease.", "Our data suggest that BBS mutations can potentiate HSCR predisposing RET alleles, which by themselves are insufficient to cause disease.", "Here, we report 3 families with BBS and HSCR with concomitant mutations in BBS genes and regulatory RET elements, whose functionality is tested in physiologically relevant assays", "Our data suggest that BBS mutations can potentiate HSCR predisposing RET alleles, which by themselves are insufficient to cause disease", "Here, we report 3 families with BBS and HSCR with concomitant mutations in BBS genes and regulatory RET elements, whose functionality is tested in physiologically relevant assays" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/19666486" ]

[]

[ "http://www.disease-ontology.org/api/metadata/DOID:10487" ]

[ "Dishevelled (Xdsh) controls cell fate via canonical Wnt signaling" ]

[ "Wnt signaling" ]

[ "Wnt signaling is known to be important for diverse embryonic and post-natal cellular events and be regulated by the proteins Dishevelled and Axin. Although Dishevelled is activated by Wnt and involved in signal transduction, it is not clear how Dishevelled-mediated signaling is turned off. ", "The Dishevelled protein mediates several diverse biological processes. Intriguingly, within the same tissues where Xenopus Dishevelled (Xdsh) controls cell fate via canonical Wnt signaling,", "Dishevelled (DVL) proteins, three of which have been identified in humans, are highly conserved components of canonical and noncanonical Wnt signaling pathways." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/25358879", "http://www.ncbi.nlm.nih.gov/pubmed/15936275", "http://www.ncbi.nlm.nih.gov/pubmed/19561403" ]

[]

[]

[ "Anderson-Fabry disease (referred to as Fabry disease) is an X-linked disorder characterized by a deficiency of the lysosomal enzyme alpha-galactosidase A and the subsequent accumulation in various tissues of globotriaosylceramide (Gb(3)), the main substrate of the defective enzyme." ]

[ "alpha-galactosidase A" ]

[ "The lysosomal storage disorder Fabry disease is characterized by excessive globotriaosylceramide (Gb3) accumulation in major organs such as the heart and kidney. Defective lysosomal alpha-galactosidase A (Gla) is responsible for excessive Gb3 accumulation, and one cell sensitive to the effects of Gb3 accumulation is vascular endothelium.", "Anderson-Fabry disease (referred to as Fabry disease) is an X-linked disorder characterized by a deficiency of the lysosomal enzyme alpha-galactosidase A and the subsequent accumulation in various tissues of globotriaosylceramide (Gb(3)), the main substrate of the defective enzyme.", "Human alpha-galactosidase A (EC 3.2.1.22; alpha-Gal A) is the lysosomal exoglycosidase responsible for the hydrolysis of terminal alpha-galactosyl residues from glycoconjugates and is the defective enzyme causing Fabry disease (McKusick 301500).", "Transgenic mice expressing a human mutant alpha-galactosidase with an R301Q substitution, which was found in a patient with a variant form of Fabry disease, were established." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/19202000", "http://www.ncbi.nlm.nih.gov/pubmed/9323559", "http://www.ncbi.nlm.nih.gov/pubmed/15533650", "http://www.ncbi.nlm.nih.gov/pubmed/19146893", "http://www.ncbi.nlm.nih.gov/pubmed/15702403", "http://www.ncbi.nlm.nih.gov/pubmed/9395081" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D008247", "http://www.disease-ontology.org/api/metadata/DOID:3211", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016464", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0005764", "http://www.disease-ontology.org/api/metadata/DOID:14499", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D000795" ]

[ "In some studies of breast cancer, quantitation of immunohistochemically highlighted microvessel ‘hot spots’ has been shown to be a powerful prognostic tool. However, the antibody used, the number and size of the ‘hot spots’ assessed, and the stratification of patients into high and low vascular groups vary between studies. Furthermore, little is known about the relationship between microvessel density and other vascular parameters. These uncertainties and the laborious nature of the technique make it unsuitable for diagnostic practice. Both manual and computerized image analysis techniques were used in this study to examine the relationship between microvessel density and the vascular parameters in different sized microscopic fields in a pilot series of 30 invasive breast carcinomas. Automated pixel analysis of immunohistochemical staining, Chalkley point counting, and observer subjective vascular grading were also assessed as more rapid methods of measuring tumour vascularity" ]

[ "yes" ]

[ "The LIM homeobox gene Lhx2 is expressed in cortical progenitors during development and also in the superficial layers of the neocortex in maturity. However, analysis of Lhx2 function at later stages of cortical development has been hampered by severe phenotypes associated with early loss of function. ", "The vein graft samples were obtained on each time point after surgery. The expression of the EDRz transfected in the vein graft was detected using a fluorescent microscope. Early growth response gene-1 (Egr-1) mRNA was measured using reverse transcription-PCR and in situ hybridization. And the protein expression of Egr-1 was detected by using western blot and immunohistochemistry analyses.", "Tissue Transglutaminase (TG2) is a multifunctional enzyme, which amongst other functions, is involved in cell differentiation. Therefore, we hypothesized that TG2 contributes to differentiation of OPCs into OLGs and thereby stimulates remyelination. " ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/21818782", "http://www.ncbi.nlm.nih.gov/pubmed/23625497", "http://www.ncbi.nlm.nih.gov/pubmed/22114700", "http://www.ncbi.nlm.nih.gov/pubmed/20663194", "http://www.ncbi.nlm.nih.gov/pubmed/20588996", "http://www.ncbi.nlm.nih.gov/pubmed/24003130", "http://www.ncbi.nlm.nih.gov/pubmed/23586030", "http://www.ncbi.nlm.nih.gov/pubmed/24262147" ]

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[ "http://www.disease-ontology.org/api/metadata/DOID:4943", "http://www.uniprot.org/uniprot/HCP_ECOSE", "http://www.uniprot.org/uniprot/GFP_AEQVI", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D007150", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D017403", "http://www.uniprot.org/uniprot/HCP_CLOB1", "http://www.uniprot.org/uniprot/HCP_ENT38", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005453" ]

[ "Yes, TALEN is being used on stem cells for genome editing." ]

[ "yes" ]

[ "Precise correction of the dystrophin gene in duchenne muscular dystrophy patient induced pluripotent stem cells by TALEN and CRISPR-Cas9.", "Genetic correction of patient-derived induced pluripotent stem cells (iPSCs) by TALENs or CRISPR-Cas9 holds promise for DMD gene therapy; however, the safety of such nuclease treatment must be determined.", "We generated helper-dependent, capsid-modified adenovirus (HD-Ad5/35) vectors for zinc-finger nuclease (ZFN)- or transcription activator-like effector nuclease (TALEN)-mediated genome editing in human CD34+ hematopoietic stem cells (HSCs) from mobilized adult donors. ", "We used transcription activator-like effector nuclease (TALEN)-mediated gene editing in mouse embryonic stem cells (mESCs) to produce mice with targeted gene disruptions and insertions in two Y-linked genes--Sry and Uty.", "Transcription activator-like effector nuclease (TALEN)-mediated gene correction in integration-free β-thalassemia induced pluripotent stem cells.", "A TALEN genome-editing system for generating human stem cell-based disease models.", "Low incidence of off-target mutations in individual CRISPR-Cas9 and TALEN targeted human stem cell clones detected by whole-genome sequencing.", "Using CRISPR-Cas9 and TALEN targeted human pluripotent stem cell clones, we performed whole-genome sequencing at high coverage in order to assess the degree of mutagenesis across the entire genome.", "A modified TALEN-based system for robust generation of knock-out human pluripotent stem cell lines and disease models.", "In this study, we utilized a cell-penetrating peptide-based system for ZFN and TALEN delivery.", "At all loci tested we obtained human embryonic stem cell (ESC) and induced pluripotent stem cell (iPSC) clones carrying transgenic cassettes solely at the TALEN-specified location.", "We report here the use of TALENs to rapidly and efficiently generate mutant alleles of 15 genes in cultured somatic cells or human pluripotent stem cells, the latter for which we differentiated both the targeted lines and isogenic control lines into various metabolic cell types.", "Zinc-finger nucleases (ZFNs) and transcription activator-like effector nucleases (TALENs) have been successfully used to knock out endogenous genes in stem cell research.", "Here we report different methods to efficiently perform TALEN-mediated gene integration and inactivation in different mammalian cell systems including induced pluripotent stem cells and delineate experimental examples associated with these approaches", "Together, our results demonstrate that TALE-based transcriptional repressor and TALENs are two promising approaches for loss-of-function studies of microRNA clusters in somatic cells and pluripotent stem cells", "We report here the use of TALENs to rapidly and efficiently generate mutant alleles of 15 genes in cultured somatic cells or human pluripotent stem cells, the latter for which we differentiated both the targeted lines and isogenic control lines into various metabolic cell types", "TALEN-mediated generation and genetic correction of disease-specific human induced pluripotent stem cells.", "Baculoviral transduction facilitates TALEN-mediated targeted transgene integration and Cre/LoxP cassette exchange in human-induced pluripotent stem cells.", "We used transcription activator-like effector nuclease (TALEN)-mediated gene editing in mouse embryonic stem cells (mESCs) to produce mice with targeted gene disruptions and insertions in two Y-linked genes--Sry and Uty. ", "Using CRISPR-Cas9 and TALEN targeted human pluripotent stem cell clones, we performed whole-genome sequencing at high coverage in order to assess the degree of mutagenesis across the entire genome. ", "A 5% modification rate was observed in human induced pluripotent stem cells (hiPSCs) treated with TAT-TALEN as measured by the Surveyor assay. TAT-TALEN protein-mediated gene disruption was applicable in hiPSCs and represents a promising technique for gene knockout in stem cells.", "Here we engineered transcription activator-like effector nucleases (TALENs) for five distinct genomic loci. At all loci tested we obtained human embryonic stem cell (ESC) and induced pluripotent stem cell (iPSC) clones carrying transgenic cassettes solely at the TALEN-specified location.", "Seamless correction of the sickle cell disease mutation of the HBB gene in human induced pluripotent stem cells using TALENs.", "At all loci tested we obtained human embryonic stem cell (ESC) and induced pluripotent stem cell (iPSC) clones carrying transgenic cassettes solely at the TALEN-specified location. Our data suggest that TALENs employing the specific architectures described here mediate site-specific genome modification in human pluripotent cells with similar efficiency and precision as do zinc-finger nucleases (ZFNs)." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/24305178", "http://www.ncbi.nlm.nih.gov/pubmed/24206569", "http://www.ncbi.nlm.nih.gov/pubmed/25245091", "http://www.ncbi.nlm.nih.gov/pubmed/25408877", "http://www.ncbi.nlm.nih.gov/pubmed/24155235", "http://www.ncbi.nlm.nih.gov/pubmed/24319658", "http://www.ncbi.nlm.nih.gov/pubmed/24691488", "http://www.ncbi.nlm.nih.gov/pubmed/25434822", "http://www.ncbi.nlm.nih.gov/pubmed/26052525", "http://www.ncbi.nlm.nih.gov/pubmed/23246482", "http://www.ncbi.nlm.nih.gov/pubmed/24996167", "http://www.ncbi.nlm.nih.gov/pubmed/23928856", "http://www.ncbi.nlm.nih.gov/pubmed/23666012", "http://www.ncbi.nlm.nih.gov/pubmed/25414332", "http://www.ncbi.nlm.nih.gov/pubmed/23921522", "http://www.ncbi.nlm.nih.gov/pubmed/23945944", "http://www.ncbi.nlm.nih.gov/pubmed/21738127", "http://www.ncbi.nlm.nih.gov/pubmed/22749015" ]

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[ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013234", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D002477" ]

[ "There is an association between bruxism and reflux." ]

[ "yes" ]

[ "Rhythmic masticatory muscle activity, including sleep bruxism (SB), can be induced in healthy individuals by experimental esophageal acidification, which plays an important role in the pathogenesis of gastroesophageal reflux disease (GERD). However, no robust evidence supports the association between SB and GERD.", "Sleep bruxism is prevalent in GERD patients, and GERD is highly associated with SB.", "Our large-scale cross-sectional study found that problem behaviors in adolescents were associated with sleep problems, including sleep bruxism, as well as lifestyle and food habits and GERD symptoms.", "The frequencies of EMG bursts, rhythmic masticatory muscle activity (RMMA) episodes, grinding noise, and the RMMA/microarousal ratio were significantly higher in the 20-minute period after acidic infusion than after saline infusion. RMMA episodes including SB were induced by esophageal acidification. ", "Direct restorative treatment of dental erosion caused by gastroesophageal reflux disease associated with bruxism:", "This article presents a case report of a 27-year-old male smoker with tooth wear and dentin sensitivity caused by GERD associated with bruxism", "Dental wear caused by association between bruxism and gastroesophageal reflux disease:", "This paper presents a case report in which bruxism associated with acid feeding, smoking habit and episodes of gastric reflow caused severe tooth wear and great muscular discomfort with daily headache episodes.", "most jaw muscle activities, ie, RMMA, single short-burst, and clenching episodes, occur in relation to gastroesophageal reflux mainly in the supine position.", "Association between nocturnal bruxism and gastroesophageal reflux.", "Nocturnal bruxism may be secondary to nocturnal gastroesophageal reflux, occurring via sleep arousal and often together with swallowing." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/15520695", "http://www.ncbi.nlm.nih.gov/pubmed/19089153", "http://www.ncbi.nlm.nih.gov/pubmed/23738993", "http://www.ncbi.nlm.nih.gov/pubmed/23937680", "http://www.ncbi.nlm.nih.gov/pubmed/24011800", "http://www.ncbi.nlm.nih.gov/pubmed/14655925", "http://www.ncbi.nlm.nih.gov/pubmed/21248360", "http://www.ncbi.nlm.nih.gov/pubmed/19830044" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D057045", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004942", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D002012", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D020186", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005764" ]

[ "Ischemia-reperfusion injury is a strong stimulus for both global and focal cardiomyocyte progenitor cell marker up-regulations, correlating to the endogenous up-regulation of IGF-1. Furthermore, in an animal model of myocardial infarction, intracoronary administration of IGF-1 is shown to reduce pathological cardiac remodeling, induce myocardial regeneration, and improve ventricular function. IGF-1 is a potent modulator of stem cell replication, commitment to the myocyte lineage, and myocyte differentiation. In another study, the dual delivery of IGF-1 and HGF from affinity-binding alginate biomaterial prevented cell apoptosis, induced cardiomyocyte cell cycle re-entry and increased the incidence of GATA-4-positive cell clusters. The addition of nanofiber-mediated IGF-1 delivery to Cardiac Progenitor Cells therapy improved in part the recovery of myocardial structure and function after infarction. IGF-1 promotes proliferation and survival of CPCs. The strategy of IGF-1 transgene expression has shown to induce massive stem cell mobilization via SDF-1alpha signaling and culminated in extensive angiomyogenesis in the infarcted heart." ]

[]

[ "In conclusion, ischemia-reperfusion injury was the strongest stimulus with both global and focal cardiomyocyte progenitor cell marker up-regulations, correlating to the endogenous up-regulation of the growth factors IGF-1 and HGF. Also pregnancy induced a general up-regulation of c-Kit and early Nkx2.5+ cardiomyocytes throughout the heart. Utilization of these pathways could provide new strategies for the treatment of cardiac disease.", "Together, our data demonstrate that the paracrine regulation of cardiac miRNAs by transplanted BMCs contributes to the protective effects of cell therapy. BMCs release IGF-1, which inhibits the processing of miR-34a, thereby blocking cardiomyocyte apoptosis.", "In an animal model of AMI relevant to the human disease, intracoronary administration of IGF-1/HGF is a practical and effective strategy to reduce pathological cardiac remodeling, induce myocardial regeneration, and improve ventricular function.", "hCSCs expressing only IGF-1R synthesize both IGF-1 and IGF-2, which are potent modulators of stem cell replication, commitment to the myocyte lineage, and myocyte differentiation, which points to this hCSC subset as the ideal candidate cell for the management of human heart failure.", "In physiologic conditions, cardiac overexpression of the IGF-1Ea propeptide is associated with an enrichment of c-Kit/Sca-1 positive side population cells in the bone marrow and the occurrence of an endothelial-primed CD34 positive side population in the heart. This cellular profile is shown here to correlate with the expression of cytokines involved in stem cell mobilization and vessel formation. This molecular and cellular interplay favored IGF-1Ea-mediated vessel formation in injured hearts. ", "Furthermore, this treatment prevented cell apoptosis, induced cardiomyocyte cell cycle re-entry and increased the incidence of GATA-4-positive cell clusters. The dual delivery of IGF-1 and HGF from affinity-binding alginate biomaterial represents a useful strategy to treat MI. It showed a marked therapeutic efficacy at various tissue levels, as well as potential to induce endogenous regeneration of cardiac muscle.", "Finally, neuregulins and periostin are proteins that induce cell-cycle reentry of cardiomyocytes, and growth factors like IGF-1 can induce growth and differentiation of stem cells. ", "The addition of nanofiber-mediated IGF-1 delivery to CPC therapy improved in part the recovery of myocardial structure and function after infarction.", "In conclusion, the strategy of IGF-1 transgene expression induced massive stem cell mobilization via SDF-1alpha signaling and culminated in extensive angiomyogenesis in the infarcted heart.", "We tested whether cardiac progenitor cells (CPCs) implanted in proximity of healed infarcts or resident CPCs stimulated locally by hepatocyte growth factor and insulin-like growth factor-1 invade the scarred myocardium and generate myocytes and coronary vessels improving the hemodynamics of the infarcted heart. Hepatocyte growth factor is a powerful chemoattractant of CPCs, and insulin-like growth factor-1 promotes their proliferation and survival. ", "Alternatively, growth factors may be delivered locally to stimulate resident CPCs and promote myocardial regeneration. ", "supplemental mIGF-1 expression did not perturb normal cardiac growth and physiology. Restoration of cardiac function in post-infarct mIGF-1 transgenic mice was facilitated by modulation of the inflammatory response and increased antiapoptotic signaling. mIGF-1 ventricular tissue exhibited increased proliferative activity several weeks after injury. ", "Cardiac stem cells and early committed cells (CSCs-ECCs) express c-Met and insulin-like growth factor-1 (IGF-1) receptors and synthesize and secrete the corresponding ligands, hepatocyte growth factor (HGF) and IGF-1. HGF mobilizes CSCs-ECCs and IGF-1 promotes their survival and proliferation. ", "After infarction, HGF and IGF-1 were injected intramyocardially to stimulate resident cardiac progenitor cells. ", "These results suggest that strategies capable of activating the growth reserve of the myocardium may be important in cardiac repair after ischemic injury.", "In conclusion, constitutive overexpression of IGF-1 prevented activation of cell death in the viable myocardium after infarction, limiting ventricular dilation, myocardial loading, and cardiac hypertrophy." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/22403243", "http://www.ncbi.nlm.nih.gov/pubmed/21546606", "http://www.ncbi.nlm.nih.gov/pubmed/15951423", "http://www.ncbi.nlm.nih.gov/pubmed/9329962", "http://www.ncbi.nlm.nih.gov/pubmed/21621517", "http://www.ncbi.nlm.nih.gov/pubmed/17525368", "http://www.ncbi.nlm.nih.gov/pubmed/18948617", "http://www.ncbi.nlm.nih.gov/pubmed/19704095", "http://www.ncbi.nlm.nih.gov/pubmed/17805990", "http://www.ncbi.nlm.nih.gov/pubmed/21723061", "http://www.ncbi.nlm.nih.gov/pubmed/22590612", "http://www.ncbi.nlm.nih.gov/pubmed/16141414", "http://www.ncbi.nlm.nih.gov/pubmed/18556576", "http://www.ncbi.nlm.nih.gov/pubmed/20889201", "http://www.ncbi.nlm.nih.gov/pubmed/16698918", "http://www.ncbi.nlm.nih.gov/pubmed/20607468", "http://www.ncbi.nlm.nih.gov/pubmed/17045939" ]

[]

[ "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=D012038", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D007334" ]

[ "Screening for early disease has been available for many years, but there is still no national screening programme established in the United Kingdom. Two systematic reviews have concluded that screening should not be carried out. In general, this recommendation has been accepted in the United Kingdom." ]

[]

[ "Introduction of PSA screening will increase total healthcare costs for prostate cancer substantially, of which the actual screening costs will be a small part.", "The vast majority of citizens in nine European countries systematically overestimate the benefits of mammography and PSA screening. In the countries investigated, physicians and other information sources appear to have little impact on improving citizens' perceptions of these benefits.", "National systematic prostate cancer screening programmes outside randomised clinical trial settings have not been implemented to date owing to lack of robust evidence that such programmes would improve survival and/or quality of life in men with screen-detected disease.", "In the case of prostate cancer screening, two systematic reviews have concluded that screening should not be carried out. In general, this recommendation has been accepted in the United Kingdom.", "Screening for early disease has been available for many years, but there is still no national screening programme established in the United Kingdom. ", "the positive predictive value of PSA screening in BRCA mutation carriers is high and that screening detects clinically significant prostate cancer.", "Web-based decision aids are known to have an effect on knowledge, attitude, and behavior; important components of informed decision making", "Increased usage of Prosdex leads to more informed decision making, the key aim of the UK Prostate Cancer Risk Management Programme. ", "Prostate specific antigen (PSA) was introduced as a prostate cancer screening tool more than 20 years ago. However, there is continuing debate regarding its utility in screening for prostate cancer. Mass screening is costly, may result in the diagnosis and treatment of prostate cancers that never become clinically significant, and the evidence of a subsequent reduction in mortality is inconclusive. In addition to its role in screening, PSA is also used to monitor the progression of the disease, both localized and metastatic. Although the evidence is contradictory, PSA is still an important tool for monitoring patient progression following treatment of definitive localized prostate cancer." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/11495383", "http://www.ncbi.nlm.nih.gov/pubmed/20507844", "http://www.ncbi.nlm.nih.gov/pubmed/20840664", "http://www.ncbi.nlm.nih.gov/pubmed/19904272", "http://www.ncbi.nlm.nih.gov/pubmed/19671770", "http://www.ncbi.nlm.nih.gov/pubmed/20060331", "http://www.ncbi.nlm.nih.gov/pubmed/17826892", "http://www.ncbi.nlm.nih.gov/pubmed/23728749" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011471", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D006113", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D055088" ]

[ "Yes, peptide aptamers can be used as inhibitors." ]

[ "yes" ]

[ "Peptide aptamers of LIM-only protein 2 (Lmo2) were previously used to successfully treat Lmo2-induced tumours in a mouse model of leukaemia.", "Inhibition of mammalian cell proliferation by genetically selected peptide aptamers that functionally antagonize E2F activity.", "Accumulating work over the past decade has shown that peptide aptamer screening represents a valid strategy for inhibitor identification that can be applied to a variety of different targets. ", ". The target of one inhibitor peptide, Pep80, identified in this screen was determined to be Snapin, a protein associated with the soluble N-ethyl maleimide sensitive factor adaptor protein receptor (SNARE) complex that is critical for calcium-dependent exocytosis during neurotransmission. ", "Use of the genetically selected intracellular aptamer inhibitors allowed us to define unique mechanisms important to HIV-1 replication and T cell biology.", "This review will describe pre-clinical and clinical data of four major classes of TGF-β inhibitor, namely i) ligand traps, ii) antisense oligonucleotides, iii) receptor kinase inhibitors and iv) peptide aptamers. ", " A peptide aptamer (ID1/3-PA7) has been designed to prevent this interaction and thereby leading to the transcription of p16(INK4a).", "A peptide kinase inhibitor (IP(20)) was used as the aptameric peptide ", "Peptide aptamer mimicking RAD51-binding domain of BRCA2 inhibits DNA damage repair and survival in Trypanosoma brucei.", " peptide aptamer, Id1/3-PA7, targeting Id1 and Id3,", "Targeting Id1 and Id3 by a specific peptide aptamer induces E-box promoter activity, cell cycle arrest, and apoptosis in breast cancer cells.", "Aptamer-derived peptides as potent inhibitors of the oncogenic RhoGEF Tgat.", "Our approach thus demonstrates that peptide aptamers are potent inhibitors that can be used to interfere with RhoGEF functions in vivo.", "Development of systemic in vitro evolution and its application to generation of peptide-aptamer-based inhibitors of cathepsin E.", "he fusion peptide, TA aptamer, was observed within PC12 cytoplasm and maintained both Abeta-binding ability and antioxygenic property similar to TRX.", "Stable expression of a novel fusion peptide of thioredoxin-1 and ABAD-inhibiting peptide protects PC12 cells from intracellular amyloid-beta.", "In order to efficiently select aptamers that bind to and inhibit proteins,", "Aptamer selection based on inhibitory activity using an evolution-mimicking algorithm.", "This demonstrates the utility of this strategy for screening aptamers based on their inhibitory actions.", "Intracellular expression of the DRD-binding peptide aptamer specifically suppressed receptor-mediated extrinsic apoptosis but not intrinsic pathway, which was recapitulated by the antisense oligonucleotides for FLASH. ", "Peptide aptamers are peptides constrained and presented by a scaffold protein that are used to study protein function in cells. They are able to disrupt protein-protein interactions ", "Here we have used a genetic screen in yeast to select in vivo peptides coupled to thioredoxin, called aptamers, that could inhibit GEFD2 activity. One aptamer, TRIAPalpha (TRio Inhibitory APtamer), specifically blocks GEFD2-exchange activity on RhoA in vitro.", "These results show that cell proliferation can be inhibited using genetically-selected synthetic peptides that specifically target protein-protein interaction motifs within cell cycle regulators.", "These data highlight the utility of peptide aptamers to identify novel binding interfaces and highlight a role for MAP1B in DAPK-1-dependent signaling in autophagy and membrane blebbing." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/20842131", "http://www.ncbi.nlm.nih.gov/pubmed/21296653", "http://www.ncbi.nlm.nih.gov/pubmed/22811618", "http://www.ncbi.nlm.nih.gov/pubmed/22956136", "http://www.ncbi.nlm.nih.gov/pubmed/17917077", "http://www.ncbi.nlm.nih.gov/pubmed/16581027", "http://www.ncbi.nlm.nih.gov/pubmed/18195017", "http://www.ncbi.nlm.nih.gov/pubmed/19150354", "http://www.ncbi.nlm.nih.gov/pubmed/22714536", "http://www.ncbi.nlm.nih.gov/pubmed/10439043", "http://www.ncbi.nlm.nih.gov/pubmed/19389625", "http://www.ncbi.nlm.nih.gov/pubmed/24130701", "http://www.ncbi.nlm.nih.gov/pubmed/18186614", "http://www.ncbi.nlm.nih.gov/pubmed/20191379", "http://www.ncbi.nlm.nih.gov/pubmed/12123800", "http://www.ncbi.nlm.nih.gov/pubmed/22533554", "http://www.ncbi.nlm.nih.gov/pubmed/16815302", "http://www.ncbi.nlm.nih.gov/pubmed/16139842", "http://www.ncbi.nlm.nih.gov/pubmed/24188027" ]

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[ "http://www.uniprot.org/uniprot/INH_BPT4", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D010455", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011500", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D052158" ]

[ "caspase-1\ncaspase-4\ncaspase-5" ]

[ "caspase-1", "caspase-4", "caspase-5" ]

[ " In addition to identifying caspases-4 and -5 as potential targets for limiting intestinal inflammation, this study has identified epithelial-expressed caspases-4 and -5 as biomarkers with diagnostic and therapeutic potential in CRC.", "However, the involvement of two related inflammatory caspase members, caspases-4 and -5, during intestinal homeostasis and disease has not yet been established. This study demonstrates that caspases-4 and -5 are involved in IBD-associated intestinal inflammation.", "Altered activity of caspases, particularly caspase-1, has been implicated in the development of intestinal diseases, such as inflammatory bowel disease (IBD) and colorectal cancer (CRC)", "In contrast, engagement of various PRR in the recently identified inflammasome complexes lead to activation of a cysteine protease, caspase-1. ", "ctivation of inflammatory caspase proteases. One such caspase, CASPASE-1 (CASP1), ", "Inflammasomes are cytosolic multiprotein complexes assembled by intracellular nucleotide-binding oligomerization domain (NOD)-like receptors (NLRs) and they initiate innate immune responses to invading pathogens and danger signals by activating caspase-1 (ref. 1).", "e activation of inflammasome by different stimuli triggers the proteolytic cleavage of pro-caspase 1 into active caspase 1", "Formation of the inflammasome can lead to the activation of inflammatory caspases, such as Caspase-1, which then activate pro-inflammatory cytokines by proteolytic cleavage. ", "inflammatory caspase-1 ", "Human caspase-5 is classified as an inflammatory caspase, although its substrate has not been identified yet.", "e inflammatory Caspase-1 ", "the inflammatory caspase-1 ", "Although it is conventionally regarded as an inflammatory caspase, recent studies have shown that caspase-4 plays a role in induction of apoptosis by endoplasmic reticulum (ER) stress. " ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/21051981", "http://www.ncbi.nlm.nih.gov/pubmed/20401526", "http://www.ncbi.nlm.nih.gov/pubmed/22195746", "http://www.ncbi.nlm.nih.gov/pubmed/23215645", "http://www.ncbi.nlm.nih.gov/pubmed/19927353", "http://www.ncbi.nlm.nih.gov/pubmed/24280500", "http://www.ncbi.nlm.nih.gov/pubmed/22895188", "http://www.ncbi.nlm.nih.gov/pubmed/20514521", "http://www.ncbi.nlm.nih.gov/pubmed/25943872", "http://www.ncbi.nlm.nih.gov/pubmed/20541850", "http://www.ncbi.nlm.nih.gov/pubmed/21880711", "http://www.ncbi.nlm.nih.gov/pubmed/20401456" ]

[]

[]

[ "Ultraconserved elements have been identified in the following genomes of invertebrates: tunicates, diptera, worm and yeast." ]

[ "tunicates", "diptera", "worm", "yeast" ]

[ "Highly conserved elements discovered in vertebrates are present in non-syntenic loci of tunicates", "To trace the history of non-coding elements, which may represent candidate ancestral cis-regulatory modules affirmed during chordate evolution, we have searched for conserved elements in tunicate and vertebrate (Olfactores) genomes. We identified, for the first time, 183 non-coding sequences that are highly conserved between the two groups", "In a recent study that identified highly evolutionary conserved sequences in three genomes of Diptera species we described an ultraconserved element found at an internal exon-intron junction of the Drosophila melanogaster homothorax (hth) gene that appeared to be involved in the control of hth pre-mRNA splicing", "We have explored the distributions of fully conserved ungapped blocks in genome-wide pair-wise alignments of recently completed species of Drosophila: D. melanogaster, D. yakuba, D. ananassae, D. pseudoobscura, D. virilis, and D. mojavensis", "Parallel searches have been performed with multiple alignments of four insect species (three species of Drosophila and Anopheles gambiae), two species of Caenorhabditis, and seven species of Saccharomyces. Conserved elements were identified with a computer program called phastCons, which is based on a two-state phylogenetic hidden Markov model ", "Ultraconserved elements in insect genomes", "Here, we used similar methods to identify ultraconserved genomic regions between the insect species Drosophila melanogaster and Drosophila pseudoobscura, as well as the more distantly related Anopheles gambiae", "Here, we identified a wide range of ultraconserved elements common to distant species, from primitive aquatic organisms to terrestrial species with complicated body systems, including some novel elements conserved in fruit fly and human.", "RESULTS: Here, we identified a wide range of ultraconserved elements common to distant species, from primitive aquatic organisms to terrestrial species with complicated body systems, including some novel elements conserved in fruit fly and human." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/16024819", "http://www.ncbi.nlm.nih.gov/pubmed/23217155", "http://www.ncbi.nlm.nih.gov/pubmed/16697139", "http://www.ncbi.nlm.nih.gov/pubmed/15899965", "http://www.ncbi.nlm.nih.gov/pubmed/18514361", "http://www.ncbi.nlm.nih.gov/pubmed/17114937", "http://www.ncbi.nlm.nih.gov/pubmed/23393190" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D007448" ]

[ "Neutrophil elastase gene (ELANE) mutations are responsible for the majority of cases of severe congenital neutropenia (SCN) and cyclic neutropenia (CN).", "Cyclic neutropenia (CN) and severe congenital neutropenia (SCN) are disorders of neutrophil production that differ markedly in disease severity. Mutations of the ELANE gene (the symbol recently replacing ELA2) are considered largely responsible for most cases of CN and SCN, but specific mutations are typically associated with one or the other " ]

[ "The neutrophil elastase gene (ELANE)" ]

[ "Neutrophil elastase gene (ELANE) mutations are responsible for the majority of cases of severe congenital neutropenia (CN) and cyclic neutropenia (CyN)", "We screened CN (n = 395) or CyN (n = 92) patients for ELANE mutations and investigated the impact of mutations on mRNA expression, protein expression, and activity. We found 116 different mutations in 162 (41%) CN patients and 26 in 51 (55%) CyN patients, 69 of them were novel", "Cyclic neutropenia and severe congenital neutropenia in patients with a shared ELANE mutation and paternal haplotype", "Cyclic neutropenia (CN) and severe congenital neutropenia (SCN) are disorders of neutrophil production that differ markedly in disease severity. Mutations of the ELANE gene (the symbol recently replacing ELA2) are considered largely responsible for most cases of CN and SCN, but specific mutations are typically associated with one or the other", "One patient with CN had the same S97L ELANE mutation as seven patients with the SCN phenotype", "Three familial cases of each of severe congenital neutropenia (SCN) and cyclic neutropenia (CN) in addition to 3 sporadic cases of SCN were analyzed for neutrophil elastase (Ela2) gene mutation", "Three cases of familial SCN (P13L, R52P, and S97L), 2 of familial CN (W212stop and P110L), and 1 of sporadic SCN (V72M) were shown to have heterozygous mutations in the Ela2 gene", "Recent studies have elucidated a role for the unfolded protein response in mediating the pathogenic effects of ELA2 mutations, the most common mutation in severe congenital neutropenia (SCN) as well as cyclic neutropenia", "Severe congenital neutropenia (SCN) is an inborn disorder of granulopoiesis. Mutations of the ELA2 gene encoding neutrophil elastase (NE) are responsible for most cases of SCN and cyclic neutropenia (CN), a related but milder disorder of granulopoiesis", "Heterozygous mutations of the gene encoding neutrophil elastase (ELA2) have been associated with cyclic neutropenia (CN) and severe congenital neutropenia (SCN).", "The observation that mutations in the neutrophil elastase gene, which cause cyclic and severe congenital neutropenia, are associated with protease maldistribution gives some clue as to the potential importance of inhibitor proteins.", "All cases of cyclic neutropenia and most cases of severe congenital neutropenia result from heterozygous germline mutations in the gene encoding neutrophil elastase, ela2.", "Mutations in the neutrophil elastase gene were identified in all patients with cyclic neutropenia and most of the patients with severe congenital neutropenia.", "Mutations in the neutrophil elastase gene were identified in all patients with cyclic neutropenia and most of the patients with severe congenital neutropenia", "Neutrophil elastase gene (ELANE) mutations are responsible for the majority of cases of severe congenital neutropenia (CN) and cyclic neutropenia (CyN)", "This study indicates that mutations of the gene encoding neutrophil elastase are probably the most common cause for severe congenital neutropenia as well as the cause for sporadic and autosomal dominant cyclic neutropenia", "Mutations in ELA2 encoding the neutrophil granule protease, neutrophil elastase (NE), are the major cause of the 2 main forms of hereditary neutropenia, cyclic neutropenia and severe congenital neutropenia (SCN)", "Mutations of the ELA2 gene encoding neutrophil elastase (NE) are responsible for most cases of SCN and cyclic neutropenia (CN), a related but milder disorder of granulopoiesis", "Heterozygous mutations of the gene encoding neutrophil elastase (ELA2) have been associated with cyclic neutropenia (CN) and severe congenital neutropenia (SCN)" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/20582973", "http://www.ncbi.nlm.nih.gov/pubmed/19057199", "http://www.ncbi.nlm.nih.gov/pubmed/12483111", "http://www.ncbi.nlm.nih.gov/pubmed/17761833", "http://www.ncbi.nlm.nih.gov/pubmed/23463630", "http://www.ncbi.nlm.nih.gov/pubmed/19415009", "http://www.ncbi.nlm.nih.gov/pubmed/11001877", "http://www.ncbi.nlm.nih.gov/pubmed/17053055", "http://www.ncbi.nlm.nih.gov/pubmed/17107353", "http://www.ncbi.nlm.nih.gov/pubmed/11543999", "http://www.ncbi.nlm.nih.gov/pubmed/14962902" ]

[]

[ "http://www.disease-ontology.org/api/metadata/DOID:0050590" ]

[ "TGFβ is activated in the myocardium in response to injury and plays a crucial role in cardiac repair by suppressing inflammation while promoting myofibroblast phenotypic modulation and extracellular matrix deposition. In fact, upregulation of TGF-beta signaling promotes the formation of a myofibroblast-like phenotype. TGF-beta interacts with bone morphogenic protein and Wnt pathways to form a complex signaling network that is critical in regulating the fate choices of both stromal and tissue-specific resident stem cells, determining whether functional regeneration or the formation of scar tissue follows an injury. In addition, TGF-beta enhances the formation of cardiospheres and could potentially enhance the regenerative potential of adult cardiac progenitor cells." ]

[]

[ "Transforming growth factor (TGF)-beta plays a crucial role in cardiac repair by suppressing inflammation while promoting myofibroblast phenotypic modulation and extracellular matrix deposition.", "We then performed a chemical screen and identified several small molecules that increase or reduce cardiomyocyte proliferation during heart development. These compounds act via Hedgehog, Insulin-like growth factor or Transforming growth factor β signaling pathways. Direct examination of heart regeneration after mechanical or genetic ablation injuries indicated that these pathways are activated in regenerating cardiomyocytes and that they can be pharmacologically manipulated to inhibit or enhance cardiomyocyte proliferation during adult heart regeneration. ", "Transforming growth factor beta, bone morphogenic protein and Wnt pathways interact to form a complex signaling network that is critical in regulating the fate choices of both stromal and tissue-specific resident stem cells (TSCs), determining whether functional regeneration or the formation of scar tissue follows an injury. ", "In the adult heart under pressure overload, Notch inhibited the development of cardiomyocyte hypertrophy and transforming growth factor-β/connective tissue growth factor-mediated cardiac fibrosis.", "EMT and CSps formation is enhanced in the presence of transforming growth factor β1 (TGFβ1) and drastically blocked by the type I TGFβ-receptor inhibitor SB431452, indicating that TGFβ-dependent EMT is essential for the formation of these niche-like 3D-multicellular clusters. Since TGFβ is activated in the myocardium in response to injury, our data suggest that CSps formation mimics an adaptive mechanism that could potentially be enhanced to increase in vivo or ex vivo regenerative potential of adult CPCs.", "During the proliferative phase of healing, infarct fibroblasts undergo myofibroblast transdifferentiation forming stress fibers and expressing contractile proteins (such as α-smooth muscle actin). Mechanical stress, transforming growth factor (TGF)-β/Smad3 signaling and alterations in the composition of the extracellular matrix induce acquisition of the myofibroblast phenotype. ", "Collectively, this data strongly suggests Wnt3a promotes the formation of a myofibroblast-like phenotype in cultured fibroblasts, in part, by upregulating TGF-β signaling through SMAD2 in a β-catenin-dependent mechanism. As myofibroblasts are critical regulators of wound healing responses, these findings may have important implications for our understanding of normal and aberrant injury and repair events.", "Conversely, exogenous addition of TGF-beta to the wound increased VIC activation, proliferation, wound closure rate, and stress fibers. Thus, wounding activates VICs, and TGF-beta signaling modulates VIC response to injury." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/21611174", "http://www.ncbi.nlm.nih.gov/pubmed/23293297", "http://www.ncbi.nlm.nih.gov/pubmed/22982064", "http://www.ncbi.nlm.nih.gov/pubmed/22765842", "http://www.ncbi.nlm.nih.gov/pubmed/23166366", "http://www.ncbi.nlm.nih.gov/pubmed/23270300", "http://www.ncbi.nlm.nih.gov/pubmed/18620057", "http://www.ncbi.nlm.nih.gov/pubmed/18832581" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016212", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D006321", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D006335", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012038" ]

[ "Everolimus and rapamycin are chemotherapeutic agents that are used for treatment of Subependymal Giant Cell Astrocytoma." ]

[ "everolimus", "rapamycin" ]

[ "Everolimus has been approved by the FDA and the EMA for the treatment of advanced renal cell carcinoma (RCC), subependymal giant cell astrocytoma (SEGA) associated with tuberous sclerosis (TSC), pancreatic neuroendocrine tumors (PNET), in combination with exemestane in advanced hormone-receptor (HR)-positive, HER2-negative breast cancer.", "The effect of everolimus on renal angiomyolipoma in patients with tuberous sclerosis complex being treated for subependymal giant cell astrocytoma: subgroup results from the randomized, placebo-controlled, Phase 3 trial EXIST-1.", "Our objective was to evaluate everolimus, an mTOR inhibitor, in the treatment of angiomyolipoma in patients with subependymal giant cell astrocytoma (SEGA) associated with TSC. METHODS: EXamining everolimus In a Study of Tuberous Sclerosis Complex-1 (NCT00789828), a prospective, double-blind, randomized, placebo-controlled, Phase 3 study, examined everolimus in treating SEGA associated with TSC. Patients with serial SEGA growth from pre-baseline to baseline scans were randomly assigned (2:1) to receive 4.5 mg/m(2)/day everolimus (target blood trough: 5-15 ng/mL; n = 78) or placebo (n = 39). ", "CONCLUSIONS: Everolimus showed efficacy in reducing angiomyolipoma lesion volume in patients with SEGA associated with TSC.", "Everolimus has demonstrated substantial clinical benefit in randomized, controlled, phase III studies leading to approval for the treatment of advanced renal cell carcinoma, advanced neuroendocrine tumors of pancreatic origin, renal angiomyolipoma and subependymal giant-cell astrocytoma associated with tuberous sclerosis complex, as well as advanced hormone-receptor-positive (HR(+)) and human epidermal growth factor receptor-2-negative advanced breast cancer. ", "Everolimus for the treatment of subependymal giant cell astrocytoma probably causing seizure aggravation in a child with tuberous sclerosis complex: a case report.", "We are reporting on a 13.5-year-old girl with tuberous sclerosis complex (TSC) who was treated with everolimus because of giant cell astrocytoma and bilateral angiomyolipoma.", "Response of subependymal giant cell astrocytoma with spinal cord metastasis to everolimus.", "BACKGROUND: Brain subependymal giant cell astrocytomas (SEGAs) in patients with tuberous sclerosis have been reported to respond to everolimus. ", "CONCLUSIONS: We describe a rare case of metastatic SEGA, which was successfully treated with everolimus.", "Additional oncology indications for everolimus include renal angiomyolipoma with tuberous sclerosis complex and subependymal giant-cell astrocytoma.", "Everolimus is a mammalian target of rapamycin (mTOR) inhibitor approved for the treatment of advanced renal cell carcinoma, pancreatic neuroendocrine tumors, subependymal giant cell astrocytoma associated with tuberous sclerosis complex, renal angiomyolipoma and tuberous sclerosis complex, and, in combination with exemestane, for hormone receptor-positive HER2-negative advanced breast cancer after failure of treatment with letrozole or anastrozole. ", "Long-term effect of everolimus on epilepsy and growth in children under 3 years of age treated for subependymal giant cell astrocytoma associated with tuberous sclerosis complex.", "AIMS: To show the long-term safety data and the effect of everolimus treatment on epilepsy in children under the age of 3 who received everolimus for SEGAs associated with TSC. ", "CONCLUSIONS: This study suggests that everolimus is effective and safe in infants and young children with epilepsy and SEGA associated with TSC and offers a valuable treatment option.", "Everolimus long-term safety and efficacy in subependymal giant cell astrocytoma.", "OBJECTIVE: To report long-term efficacy and safety data for everolimus for the treatment of subependymal giant cell astrocytoma (SEGA) in patients with tuberous sclerosis complex (TSC).", "CONCLUSION: Everolimus therapy is safe and effective for longer term (median exposure 34.2 months) treatment of patients with TSC with SEGA. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that everolimus, titrated to trough serum levels of 5-15 ng/mL, was effective in reducing tumor size in patients with SEGA secondary to TSC for a median of 34 months.", "Everolimus (RAD001): first systemic treatment for subependymal giant cell astrocytoma associated with tuberous sclerosis complex.", "In patients with subependymal giant cell astrocytomas (SEGAs) associated with tuberous sclerosis complex who are not candidates for surgery, single-agent everolimus has demonstrated the ability to significantly reduce SEGA volume with good tolerability. In the Phase III, randomized, placebo-controlled trial, everolimus was associated with a SEGA response rate of 35% compared with 0% in the placebo group. ", "Efficacy and safety of everolimus for subependymal giant cell astrocytomas associated with tuberous sclerosis complex (EXIST-1): a multicentre, randomised, placebo-controlled phase 3 trial.", "In an open-label, phase 1/2 study, the mTOR inhibitor everolimus substantially and significantly reduced the volume of subependymal giant cell astrocytomas. We assessed the efficacy and safety of everolimus in patients with subependymal giant cell astrocytomas associated with tuberous sclerosis complex. ", "INTERPRETATION: These results support the use of everolimus for subependymal giant cell astrocytomas associated with tuberous sclerosis.", "Everolimus for tumor recurrence after surgical resection for subependymal giant cell astrocytoma associated with tuberous sclerosis complex.", "A recent phase 1/2 study demonstrated that treatment with the mammalian target of rapamycin inhibitor everolimus reduced subependymal giant cell astrocytoma volume by 30% in 75% of the patients, all of whom were poor candidates for surgical resection. ", "All 4 experienced over 50% initial reduction in the volume of their subependymal giant cell astrocytoma after 2 to 3 years of therapy with everolimus.", "METHODS: Recently, a phase I/II trial of everolimus demonstrated significant reductions in subependymal giant cell astrocytoma (SEGA) volume and decreased seizure frequency.", "TSC patients with SEGA received everolimus, titrated to tolerability to achieve target trough concentrations of 5-15 ng/mL.", "Everolimus: in patients with subependymal giant cell astrocytoma associated with tuberous sclerosis complex.", "Everolimus is an orally administered inhibitor of the mammalian target of rapamycin (mTOR). Everolimus (starting dosage 3.0 mg/m(2)) was associated with a significant reduction in the volume of the largest subependymal giant cell astrocytoma (SEGA) in 28 patients aged ≥3 years with tuberous sclerosis complex (TSC) in a phase II trial (C2485). ", "During the extension phase of this trial (median duration 34 months), the reduction in SEGA volume was maintained, with no everolimus recipient requiring surgery or other therapy for SEGA or hydrocephalus. ", "Effective everolimus treatment of inoperable, life-threatening subependymal giant cell astrocytoma and intractable epilepsy in a patient with tuberous sclerosis complex.", "We present successful everolimus treatment of a huge subependymal giant cell astrocytoma in a 10-year old boy with tuberous sclerosis complex. ", "Everolimus tablets for patients with subependymal giant cell astrocytoma.", "Recently, mTOR inhibitors such as everolimus have shown encouraging benefit for patients with SEGAs. ", "The authors also examine the rationale for targeted agents against this pathway therapeutically and describe the clinical evidence underlying the FDA approval of everolimus for patients with inoperable SEGAs. EXPERT OPINION: Everolimus (Afinitor) selectively targets a molecular defect of SEGAs in TSC patients.", "Everolimus for subependymal giant-cell astrocytomas in tuberous sclerosis.", "An alternative may be the use of everolimus, which inhibits the mammalian target of rapamycin, a protein regulated by gene products involved in the tuberous sclerosis complex.", "Everolimus therapy was associated with a clinically meaningful reduction in volume of the primary subependymal giant-cell astrocytoma, as assessed on independent central review (P<0.001 for baseline vs. 6 months), with a reduction of at least 30% in 21 patients (75%) and at least 50% in 9 patients (32%). ", "CONCLUSIONS: Everolimus therapy was associated with marked reduction in the volume of subependymal giant-cell astrocytomas and seizure frequency and may be a potential alternative to neurosurgical resection in some cases, though long-term studies are needed.", "The authors present a 21-year-old woman who has been receiving rapamycin for 5 months for bilateral subependymal giant cell astrocytomas.", "We present successful everolimus treatment of a huge subependymal giant cell astrocytoma in a 10-year old boy with tuberous sclerosis complex.", "A recent phase 1/2 study demonstrated that treatment with the mammalian target of rapamycin inhibitor everolimus reduced subependymal giant cell astrocytoma volume by 30% in 75% of the patients, all of whom were poor candidates for surgical resection.", "This review provides an overview of TSC, everolimus, and the clinical trials that led to its approval for the treatment of TSC-associated subependymal giant cell astrocytoma and renal angiomyolipoma.", "Everolimus in the treatment of subependymal giant cell astrocytomas, angiomyolipomas, and pulmonary and skin lesions associated with tuberous sclerosis complex.", "In patients with subependymal giant cell astrocytomas (SEGAs) associated with tuberous sclerosis complex who are not candidates for surgery, single-agent everolimus has demonstrated the ability to significantly reduce SEGA volume with good tolerability", "The authors also examine the rationale for targeted agents against this pathway therapeutically and describe the clinical evidence underlying the FDA approval of everolimus for patients with inoperable SEGAs." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/24667713", "http://www.ncbi.nlm.nih.gov/pubmed/23689226", "http://www.ncbi.nlm.nih.gov/pubmed/23567018", "http://www.ncbi.nlm.nih.gov/pubmed/24276039", "http://www.ncbi.nlm.nih.gov/pubmed/24293099", "http://www.ncbi.nlm.nih.gov/pubmed/24143074", "http://www.ncbi.nlm.nih.gov/pubmed/21047224", "http://www.ncbi.nlm.nih.gov/pubmed/22000822", "http://www.ncbi.nlm.nih.gov/pubmed/24729041", "http://www.ncbi.nlm.nih.gov/pubmed/22805244", "http://www.ncbi.nlm.nih.gov/pubmed/22262746", "http://www.ncbi.nlm.nih.gov/pubmed/22136276", "http://www.ncbi.nlm.nih.gov/pubmed/23231513", "http://www.ncbi.nlm.nih.gov/pubmed/18952591", "http://www.ncbi.nlm.nih.gov/pubmed/24756805", "http://www.ncbi.nlm.nih.gov/pubmed/23158522", "http://www.ncbi.nlm.nih.gov/pubmed/21806479", "http://www.ncbi.nlm.nih.gov/pubmed/24518170", "http://www.ncbi.nlm.nih.gov/pubmed/23686401", "http://www.ncbi.nlm.nih.gov/pubmed/23325902" ]

[]

[]

[ "Yes, \tintegrins are a central family of extracellular matrix receptors." ]

[ "yes" ]

[ "Several constituents of the ECM provide adhesive cues, which serve as binding sites for cell trans-membrane receptors, such as integrins.", "We also determined that blocking β1integrins, the major class of receptors for all ECM proteins tested,", "Here, we elucidate a cross-scale mechanism for tissue assembly and ECM remodeling involving Cadherin 2, the ECM protein Fibronectin, and its receptor Integrin α5. ", "due to the diverse functions and variable expression of proteoglycans, matrix proteins, and integrins, it is rather difficult to identify a comprehensive therapeutic target among ECM components.", "Integrin-dependent cell-extracellular matrix (ECM) adhesion is a determinant of spindle orientation.", "The extracellular matrix component periostin is a secreted protein that functions as both a cell attachment protein and an autocrine or paracrine factor that signals through the cell adhesion molecule integrins αvβ3 and αvβ5. ", "Integrin receptors connect the extracellular matrix to the cell cytoskeleton to provide essential forces and signals. ", " the integrin, talin, and actin filament form a linear complex of which both ends are typically anchored to the extracellular matrices via integrins.", "Integrins, a central family of cellular ECM receptors, have been implicated in these processes but their specific role in ES cell self-renewal remains unclear.", "Attachment to the extracellular matrix is mediated by a complex of adhesion proteins, including integrins, signaling molecules, actin and actin-binding proteins, and scaffolding proteins.", "Beta 1 integrin binding plays a role in the constant traction force generation in response to varying stiffness for cells grown on mature cardiac extracellular matrix." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/25220424", "http://www.ncbi.nlm.nih.gov/pubmed/26029690", "http://www.ncbi.nlm.nih.gov/pubmed/25759527", "http://www.ncbi.nlm.nih.gov/pubmed/26096733", "http://www.ncbi.nlm.nih.gov/pubmed/24965068", "http://www.ncbi.nlm.nih.gov/pubmed/26067407", "http://www.ncbi.nlm.nih.gov/pubmed/25631868", "http://www.ncbi.nlm.nih.gov/pubmed/25886986", "http://www.ncbi.nlm.nih.gov/pubmed/25605337", "http://www.ncbi.nlm.nih.gov/pubmed/25460334", "http://www.ncbi.nlm.nih.gov/pubmed/26089687" ]

[]

[]

[ "Calcium homeostasis is very important in cardiac physiology and pathophysiology. Maintenance of cellular calcium homeostasis is critical to regulating cardiac contraction. Abnormalities in calcium homeostasis underlie cardiac arrhythmia, contractile dysfunction and cardiac remodelling." ]

[ "yes" ]

[ "Maintenance of cellular calcium homeostasis is critical to regulating mitochondrial ATP production and cardiac contraction. ", "the Ca(2+) signal regulates the most important activities of the cell, from the expression of genes, to heart and muscle contraction and other motility processes, to diverse metabolic pathways involved in the generation of cell fuels", "Pharmacologic modification of cellular calcium handling recently moved into focus as an alternative for prevention and treatment of ventricular tachyarrhythmias", "diabetic rats displayed abnormal cardiac structure and systolic and diastolic dysfunction, and spermine (CaSR agonist) could prevent or slow its progression. These results indicate that the CaSR expression of myocardium is reduced in the progress of DCM, and its potential mechanism is related to the impaired intracellular calcium homeostasis.", "calcium-sensing receptor (CaSR)", "Na(+)/Ca(2+) exchanger (NCX) plays important roles in cardiac electrical activity and calcium homeostasis.", "NCX current (I(NCX)) shows transmural gradient across left ventricle in many species. Previous studies demonstrated that NCX expression was increased and transmural gradient of I(NCX) was disrupted in failing heart", "calcium homeostasis, the key process underlying excitation-contraction coupling", "The results indicate the calcium handling properties of hiPSC-derived cardiomyocytes are relatively immature to hESC counterparts", "Our understanding of the molecular processes which regulate cardiac function has grown immeasurably in recent years. Even with the advent of β-blockers, angiotensin inhibitors and calcium modulating agents, heart failure (HF) still remains a seriously debilitating and life-threatening condition. Here, we review the molecular changes which occur in the heart in response to increased load and the pathways which control cardiac hypertrophy, calcium homeostasis, and immune activation during HF.", "Calcium-sensing receptors (CaSRs) are G-protein coupled receptors which maintain systemic calcium homeostasis and participate in hormone secretion, activation of ion channels, cell apoptosis, proliferation, and differentiation.", "CaSRs are associated with I/R injury and apoptosis in neonatal rat ventricular cardiomyocytes via suppressing Bcl-2 and promoting caspase-3 expression.", "Important insights into the molecular basis of hypertrophic cardiomyopathy and related diseases have been gained by studying families with inherited cardiac hypertrophy. Integrated clinical and genetic investigations have demonstrated that different genetic defects can give rise to the common phenotype of cardiac hypertrophy. Diverse pathways have been identified, implicating perturbations in force generation, force transmission, intracellular calcium homeostasis, myocardial energetics, and cardiac metabolism in causing disease", "HAX-1 as a regulator of contractility and calcium cycling in the heart. HAX-1 overexpression reduced sarcoplasmic reticulum Ca-ATPase (SERCA2) pump activity in isolated cardiomyocytes and in vivo, leading to depressed myocyte calcium kinetics and mechanics.", "Thus, HAX-1 represents a regulatory mechanism in cardiac calcium cycling and its responses to sympathetic stimulation, implicating its importance in calcium homeostasis and cell survival.", "Calcium ions are the most ubiquitous and versatile signaling molecules in eukaryotic cells. Calcium homeostasis and signaling systems are crucial for both the normal growth of the budding yeast Saccharomyces cerevisiae and the intricate working of the mammalian heart.", "this knowledge can be used to help treat relevant human diseases such as pathological cardiac hypertrophy and heart failure", "With aging, the heart develops myocyte hypertrophy associated with impaired relaxation indices. To define the cellular basis of this adaptation, we examined the physiological changes that arise in calcium handling in the aging heart and contrasted the adaptations that occur following the imposition of a stimulus that alters calcium homeostasis in a young and an old heart", "alterations in the calcium-handling machinery of the cardiocyte differ in the context of age and as such may predispose the older heart to the development of a hypertrophic phenotype.", "The cardiac sodium-calcium exchanger (NCX1) is a key sarcolemmal protein for the maintenance of calcium homeostasis in the heart. ", "Thus exchanger overexpression in mice leads to abnormal calcium handling and a decompensatory transition to heart failure with stress", "Central to controlling intracellular calcium concentration ([Ca(2+)](i)) are a number of Ca(2+) transporters and channels with the L-type Ca(2+) channel, Na(+)-Ca(2+) exchanger and sarcoplasmic reticulum Ca(2+)-ATPase (SERCA) being of particular note in the heart. This review concentrates on the regulation of [Ca(2+)](i) in cardiac muscle and the homeostatic mechanisms employed to ensure that the heart can operate under steady-state conditions on a beat by beat basis.", "the tight regulation of SR Ca(2+) content is also required to prevent the abnormal, spontaneous or diastolic release of Ca(2+) from the SR. Such diastolic events are a major factor contributing to the genesis of cardiac arrhythmias in disease situations and in recently identified familial mutations in the SR Ca(2+) release channel (ryanodine receptor, RyR).", "Calcium channels have a unique functional role, because not only do they participate in this activity, they form the means by which electrical signals are converted to responses within the cell. Calcium channels play an integral role in excitation in the heart and shaping the cardiac action potential. In addition, calcium influx through calcium channels is responsible for initiating contraction. Abnormalities in calcium homeostasis underlie cardiac arrhythmia, contractile dysfunction and cardiac remodelling. ", "Cardiac calcium (Ca(2+)) handling subsumes the mechanisms maintaining the myocardial Ca(2+) homeostasis that contribute essentially to cardiac performance.", "Calcium is an important mediator in cardiac excitation and disorders in cardiac Ca(2+) homeostasis have great influence on the cardiac action potential.", "We review the physiology of the cardiac calcium homeostasis, including the cardiac excitation contraction coupling and myocyte calcium cycling.", "We review the physiology of the cardiac calcium homeostasis, including the cardiac excitation contraction coupling and myocyte calcium cycling", "Calcium is an important mediator in cardiac excitation and disorders in cardiac Ca(2+) homeostasis have great influence on the cardiac action potential", "The role of calcium in cardiac and vascular smooth muscle physiology was reviewed, highlighting the major mechanisms responsible for maintaining calcium homeostasis in these cells", "Energy metabolism and Ca(2+) handling serve critical roles in cardiac physiology and pathophysiology" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/23595672", "http://www.ncbi.nlm.nih.gov/pubmed/21750914", "http://www.ncbi.nlm.nih.gov/pubmed/22137362", "http://www.ncbi.nlm.nih.gov/pubmed/24657282", "http://www.ncbi.nlm.nih.gov/pubmed/19678847", "http://www.ncbi.nlm.nih.gov/pubmed/22707075", "http://www.ncbi.nlm.nih.gov/pubmed/23554644", "http://www.ncbi.nlm.nih.gov/pubmed/17517353", "http://www.ncbi.nlm.nih.gov/pubmed/7889444", "http://www.ncbi.nlm.nih.gov/pubmed/22733365", "http://www.ncbi.nlm.nih.gov/pubmed/22673935", "http://www.ncbi.nlm.nih.gov/pubmed/17353151", "http://www.ncbi.nlm.nih.gov/pubmed/19920172", "http://www.ncbi.nlm.nih.gov/pubmed/18172603", "http://www.ncbi.nlm.nih.gov/pubmed/20875630", "http://www.ncbi.nlm.nih.gov/pubmed/17509680", "http://www.ncbi.nlm.nih.gov/pubmed/20347784", "http://www.ncbi.nlm.nih.gov/pubmed/21614516" ]

[]

[ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0003301", "http://www.biosemantics.org/jochem#4277675", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0055074", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0042592" ]

[ "Ancora and TFCONES." ]

[ "Ancora", "TFCONES" ]

[ "Ancora: a web resource for exploring highly conserved noncoding elements and their association with developmental regulatory genes", " We describe Ancora http://ancora.genereg.net, a web resource that provides data and tools for exploring genomic organization of HCNEs for multiple genomes. Ancora includes a genome browser that shows HCNE locations and features novel HCNE density plots as a powerful tool to discover developmental regulatory genes and distinguish their regulatory elements and domains", "TFCONES: a database of vertebrate transcription factor-encoding genes and their associated conserved noncoding elements", " We have created a database named TFCONES (Transcription Factor Genes & Associated COnserved Noncoding ElementS) (http://tfcones.fugu-sg.org) which contains all human, mouse and fugu TF-encoding genes and conserved noncoding elements (CNEs) associated with them", "The conserved noncoding elements identified in TFCONES represent a catalog of highly prioritized putative cis-regulatory elements of TF-encoding genes and are candidates for functional assay.", "TFCONES: a database of vertebrate transcription factor-encoding genes and their associated conserved noncoding elements.", "We have created a database named TFCONES (Transcription Factor Genes & Associated COnserved Noncoding ElementS) (http://tfcones.", "We have created a database named TFCONES (Transcription Factor Genes & Associated COnserved Noncoding ElementS) (http://tfcones.fugu-sg.org) which contains all human, mouse and fugu TF-encoding genes and conserved noncoding elements (CNEs) associated with them" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/18279518", "http://www.ncbi.nlm.nih.gov/pubmed/18045502" ]

[]

[]

[ "The functional annotation of the mammalian genome 5 (FANTOM5) project provides comprehensive expression profiles and functional annotation of mammalian cell-type-specific transcriptomes with wide applications in biomedical research. The FANTOM5 and ENCODE projects represent two independent large scale efforts to map regulatory and transcriptional features to the human genome." ]

[ "To provide comprehensive expression profiles and functional annotation of mammalian cell-type-specific transcriptomes with wide applications in biomedical research." ]

[ "The FANTOM5 and ENCODE projects represent two independent large scale efforts to map regulatory and transcriptional features to the human genome.", "The functional annotation of the mammalian genome 5 (FANTOM5) project provides comprehensive expression profiles and functional annotation of mammalian cell-type-specific transcriptomes with wide applications in biomedical research", "The functional annotation of the mammalian genome 5 (FANTOM5) project provides comprehensive expression profiles and functional annotation of mammalian cell-type-specific transcriptomes with wide applications in biomedical research.", "The online FANTOM5 enhancer atlas represents a unique resource for studies on cell-type-specific enhancers and gene regulation.", "The FANTOM5 and ENCODE projects represent two independent large scale efforts to map regulatory and transcriptional features to the human genome.", "The functional annotation of the mammalian genome 5 (FANTOM5) project provides comprehensive expression profiles and functional annotation of mammalian cell-type-specific transcriptomes with wide applications in biomedical research.", "The FANTOM5 and ENCODE projects represent two independent large scale efforts to map regulatory and transcriptional features to the human genome. ", "The online FANTOM5 enhancer atlas represents a unique resource for studies on cell-type-specific enhancers and gene regulation.", "Here we use the FANTOM5 panel of samples, covering the majority of human tissues and cell types, to produce an atlas of active, in vivo-transcribed enhancers. ", "The FANTOM5 and ENCODE projects represent two independent large scale efforts to map regulatory and transcriptional features to the human genome. Here we investigate chromatin features around a comprehensive set of transcription start sites in four cell lines by integrating data from these two projects. ", "The functional annotation of the mammalian genome 5 (FANTOM5) project provides comprehensive expression profiles and functional annotation of mammalian cell-type-specific transcriptomes with wide applications in biomedical research.", "The FANTOM5 and ENCODE projects represent two independent large scale efforts to map regulatory and transcriptional features to the human genome." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/24669905", "http://www.ncbi.nlm.nih.gov/pubmed/24670763", "http://www.ncbi.nlm.nih.gov/pubmed/24670764" ]

[]

[]

[ "The human double-homeodomain retrogene DUX4 is expressed in the testis and epigenetically repressed in somatic tissues. Recent studies provide evidence that DUX4 is expressed in the human germline and then epigenetically silenced in somatic cells.", "Yes, the human double-homeodomain retrogene DUX4 is expressed in the testis and epigenetically repressed in somatic tissues.", "Recent studies provide compelling evidence that a retrotransposed gene in the D4Z4 repeat, DUX4, is expressed in the human germline and then epigenetically silenced in somatic tissues. ", "The human double-homeodomain retrogene DUX4 is expressed in the testis and epigenetically repressed in somatic tissues.DUX4, a retrogene contained in the D4Z4 repeats, is normally epigenetically silenced in somatic cells." ]

[ "yes" ]

[ "There are several genes on chromosome 4q35 region including DUX4 within D4Z4 repeats. Transcription of these genes is usually repressed by epigenetic modifications of this chromosomal region and also accumulation of transcriptional repressors to the repeat array.", "Recent studies provide compelling evidence that a retrotransposed gene in the D4Z4 repeat, DUX4, is expressed in the human germline and then epigenetically silenced in somatic tissues. ", "The human double-homeodomain retrogene DUX4 is expressed in the testis and epigenetically repressed in somatic tissues.", "Facioscapulohumeral dystrophy (FSHD) is a progressive muscular dystrophy caused by decreased epigenetic repression of the D4Z4 macrosatellite repeats and ectopic expression of DUX4, a retrogene encoding a germline transcription factor encoded in each repeat.", " These mice recapitulate important epigenetic and DUX4 expression attributes seen in patients and controls, respectively, including high DUX4 expression levels in the germline, (incomplete) epigenetic repression in somatic tissue, and FSHD-specific variegated DUX4 expression in sporadic muscle nuclei associated with D4Z4 chromatin relaxation.", "DUX4, a retrogene contained in the D4Z4 repeats, is normally epigenetically silenced in somatic cells.", "In contrast to control skeletal muscle and most other somatic tissues, full-length DUX4 transcript and protein is expressed at relatively abundant levels in human testis, most likely in the germ-line cells. Induced pluripotent (iPS) cells also express full-length DUX4 and differentiation of control iPS cells to embryoid bodies suppresses expression of full-length DUX4, whereas expression of full-length DUX4 persists in differentiated FSHD iPS cells. Together, these findings indicate that full-length DUX4 is normally expressed at specific developmental stages and is suppressed in most somatic tissues.", "Recent studies provide compelling evidence that a retrotransposed gene in the D4Z4 repeat, DUX4, is expressed in the human germline and then epigenetically silenced in somatic tissues.", "DUX4, a retrogene contained in the D4Z4 repeats, is normally epigenetically silenced in somatic cells. ", "DUX4, a retrogene contained in the D4Z4 repeats, is normally epigenetically silenced in somatic cells.", "Recent studies provide compelling evidence that a retrotransposed gene in the D4Z4 repeat, DUX4, is expressed in the human germline and then epigenetically silenced in somatic tissues.", "Normally expressed in the testis and epigenetically repressed in somatic tissues, DUX4 expression in skeletal muscle induces expression of many germline, stem cell, and other genes that might account for the pathophysiology of FSHD.", "Recent studies provide compelling evidence that a retrotransposed gene in the D4Z4 repeat, DUX4, is expressed in the human germline and then epigenetically silenced in somatic tissues", "The human double-homeodomain retrogene DUX4 is expressed in the testis and epigenetically repressed in somatic tissues", "Normally expressed in the testis and epigenetically repressed in somatic tissues, DUX4 expression in skeletal muscle induces expression of many germline, stem cell, and other genes that might account for the pathophysiology of FSHD", "DUX4, a retrogene contained in the D4Z4 repeats, is normally epigenetically silenced in somatic cells", "Recent studies provide compelling evidence that a retrotransposed gene in the D4Z4 repeat, DUX4, is expressed in the human germline and then epigenetically silenced in somatic tissues", "The identification of the gene(s) and the exact epigenetic pathway underlining this disease will be mandatory to increase the rate of diagnosis for FSHD2 patients and to confirm the hypothesis of a common FSHD1 and FSHD2 pathophysiological pathway involving DUX4 gene", "This deletion induces epigenetic modifications that affect the expression of several genes located in the vicinity. In each D4Z4 element, we identified the double homeobox 4 (DUX4) gene. DUX4 expresses a transcription factor that plays a major role in the development of FSHD through the initiation of a large gene dysregulation cascade that causes myogenic differentiation defects, atrophy and reduced response to oxidative stress. ", "decreased epigenetic repression and variegated expression of DUX4 in skeletal muscle", "(incomplete) epigenetic repression in somatic tissue,", "Facioscapulohumeral dystrophy (FSHD) is characterized by chromatin relaxation of the D4Z4 macrosatellite array on chromosome 4 and expression of the D4Z4-encoded DUX4 gene in skeletal muscle.", "derepression of the DUX4 retrogene", "The aim of our study was to identify relationships between epigenetic parameters correlating with a relaxed chromatin state of the DUX4 promoter region and clinical severity as measured by a clinical severity score or muscle pathologic changes in D4Z4 contraction-dependent (FSHD1) and -independent (FSHD2) facioscapulohumeral muscular dystrophy patients. ", "Specifically, abundance of RNA transcripts encoded by the DUX4 locus correlated to differential DNA methylation and H3K36me3 enrichment.", "Together, these findings indicate that full-length DUX4 is normally expressed at specific developmental stages and is suppressed in most somatic tissue" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/23969240", "http://www.ncbi.nlm.nih.gov/pubmed/22522912", "http://www.ncbi.nlm.nih.gov/pubmed/23196547", "http://www.ncbi.nlm.nih.gov/pubmed/23272181", "http://www.ncbi.nlm.nih.gov/pubmed/24278031", "http://www.ncbi.nlm.nih.gov/pubmed/21288772", "http://www.ncbi.nlm.nih.gov/pubmed/21734574", "http://www.ncbi.nlm.nih.gov/pubmed/23593020", "http://www.ncbi.nlm.nih.gov/pubmed/24940479", "http://www.ncbi.nlm.nih.gov/pubmed/23143600", "http://www.ncbi.nlm.nih.gov/pubmed/22871573", "http://www.ncbi.nlm.nih.gov/pubmed/22025602", "http://www.ncbi.nlm.nih.gov/pubmed/21060811" ]

[ { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A16475868", "o": "C532958" }, { "p": "http://www.w3.org/2008/05/skos-xl#prefLabel", "s": "http://linkedlifedata.com/resource/umls/id/C2607370", "o": "http://linkedlifedata.com/resource/umls/label/A16475868" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A16475868", "o": "Dux4 protein, mouse" }, { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A16475868", "o": "MeSH" }, { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A3832170", "o": "MeSH" }, { "p": "http://www.w3.org/2008/05/skos-xl#prefLabel", "s": "http://linkedlifedata.com/resource/umls/id/C1317909", "o": "http://linkedlifedata.com/resource/umls/label/A3832170" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A3832170", "o": "DUX4 protein, human" }, { "p": "http://linkedlifedata.com/resource/umls/altMetaMap", "s": "http://linkedlifedata.com/resource/umls/id/C1317909", "o": "http://linkedlifedata.com/resource/umls/label/A3840964" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A3840964", "o": "double homeobox, 4 protein, human" }, { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A3840964", "o": "MeSH" } ]

[ "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D063185", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D044127", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0040029", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0040030", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D057890", "http://www.uniprot.org/uniprot/DUX4_HUMAN", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0045858" ]

[ "Human IRG1 and mouse Irg1 mediates antiviral and antimicrobial immune responses, without its exact role having been elucidated. Irg1 has been suggested to have a role in apoptosis and to play a significant role in embryonic implantation. Irg1 is reported as the mammalian ortholog of methylcitrate dehydratase." ]

[]

[ "IRG1 is highly upregulated in murine ANA-1 macrophages by several proinflammatory cytokines and Toll-like receptor (TLR) agonists, as well as in spleen and lung of Listeria monocytogenes or Toxoplasma gondii infected mice, respectively", "The proinflammatory cytokine-induced IRG1 protein associates with mitochondria", "multiple genes induced by Borrelia burgdorferi in macrophages to regulate Lyme disease inflammation", "One of these genes, IRG1, was confirmed by single nucleotide polymorphism analysis to be involved in susceptibility. Its precise mechanism remains to be elucidated, although the analysis of gene expression data suggests it has a role in apoptosis.", "Murine immune-responsive gene 1 (IRG1) plays significant roles in embryonic implantation and neurodegeneration", "the IRG1 gene is differentially expressed in human fetal PBMCs and LPS-stimulated adult PBMCs.", "we identified the immune-responsive gene 1 (IRG1), which was expressed substantially higher in lipopolysaccharide (LPS)-stimulated than in MAP-infected murine macrophage cell lines.", "The inhibitor also blocked induction by LIF of several LIF-regulated genes in the LE including Irg1, which has been shown previously to be essential for implantation.", "Immune-responsive gene 1 is a novel target of progesterone receptor and plays a critical role during implantation in the mouse.", "our studies identified Irg1 as a novel target of PR in the pregnant uterus and also revealed that it is a critical regulator of the early events leading to implantation", " This resulted in the identification of one novel P4-regulated gene that had been previously found in lipopolysaccharide-stimulated macrophages and called immune response gene-1 (Irg1) and which is the mammalian ortholog of the bacterial gene encoding methylcitrate dehydratase", "the mammalian ortholog of methylcitrate dehydratase (immune response gene 1)", "Here we report the isolation of a complementary DNA representing a novel gene, interferon-regulated gene 1 (IRG1). T", "Here we report the isolation of a complementary DNA representing a novel gene, interferon-regulated gene 1 (IRG1). This gene exhibits significant homology to interferon (IFN)-alpha/beta-inducible human genes p27 and 6-16, indicating that these genes may belong to the same family", "The level of IRG1 mRNA again rose transiently on day 4 immediately preceding implantation.", "Although the functional roles of IRG1 and p27 remain unclear, we describe for the first time, identification of a gene family regulated by IFNalpha in both rodent and human uteri", "Hence, the induction of IRG1 by LPS is mediated by tyrosine kinase and protein kinase C pathway." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/19014335", "http://www.ncbi.nlm.nih.gov/pubmed/12893884", "http://www.ncbi.nlm.nih.gov/pubmed/21424586", "http://www.ncbi.nlm.nih.gov/pubmed/21865384", "http://www.ncbi.nlm.nih.gov/pubmed/16415166", "http://www.ncbi.nlm.nih.gov/pubmed/23455712", "http://www.ncbi.nlm.nih.gov/pubmed/11356686", "http://www.ncbi.nlm.nih.gov/pubmed/15937114", "http://www.ncbi.nlm.nih.gov/pubmed/14500577", "http://www.ncbi.nlm.nih.gov/pubmed/21947773", "http://www.ncbi.nlm.nih.gov/pubmed/7721348" ]

[]

[ "http://www.uniprot.org/uniprot/IRG1_MOUSE" ]

[ "Yes, human embryonic stem cell (hESC) therapies are being assessed for age-related macular degeneration (AMD)." ]

[ "yes" ]

[ "Development of human embryonic stem cell therapies for age-related macular degeneration", "In this review, we describe recent approaches to develop cell-based therapies for the treatment of AMD. Recent research has focused on replacing the retinal pigment epithelium (RPE), a monolayer of cells vital to photoreceptor cell health. We discuss the various methods used to differentiate and purify RPE from human embryonic stem cells (HESC), and describe the surgical approaches being used to transplant these cells in existing and forthcoming clinical trials.", "Age-related macular degeneration (AMD) is characterized by the loss or dysfunction of retinal pigment epithelium (RPE) and is the most common cause of vision loss among the elderly. Stem-cell-based strategies, using human embryonic stem cells (hESCs) or human-induced pluripotent stem cells (hiPSCs), may provide an abundant donor source for generating RPE cells in cell replacement therapies.", "This study contributes to our understanding of the utility of hESC/hiPSC-derived RPE in AMD therapy.", "Two important early potential hESC applications are the use of retinal pigment epithelium (RPE) for the treatment of age-related macular degeneration and Stargardt disease, an untreatable form of macular dystrophy that leads to early-onset blindness.", "Human embryonic stem cells (hESCs) are a promising source of retinal pigment epithelium (RPE) cells: cells that can be used for the treatment of common and incurable forms of blindness, such as age-related macular degeneration.", "A potential application of human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs) is the generation of retinal pigmented epithelium (RPE) to treat age-related macular degeneration (AMD), a common but incurable retinal disease.", "Human embryonic stem cells (hESCs) are a promising source of retinal pigment epithelium (RPE) cells: cells that can be used for the treatment of common and incurable forms of blindness, such as age-related macular degeneration", "A potential application of human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs) is the generation of retinal pigmented epithelium (RPE) to treat age-related macular degeneration (AMD), a common but incurable retinal disease", "Assessments of safety and efficacy are crucial before human ESC (hESC) therapies can move into the clinic. Two important early potential hESC applications are the use of retinal pigment epithelium (RPE) for the treatment of age-related macular degeneration and Stargardt disease, an untreatable form of macular dystrophy that leads to early-onset blindness.", "A potential application of human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs) is the generation of retinal pigmented epithelium (RPE) to treat age-related macular degeneration (AMD), a common but incurable retinal disease. RPE cells derived from hESCs (hESC-RPEs) and iPSCs (iPSC-RPEs) express essential RPE markers and can rescue visual function in animal models.", "Two important early potential hESC applications are the use of retinal pigment epithelium (RPE) for the treatment of age-related macular degeneration and Stargardt disease, an untreatable form of macular dystrophy that leads to early-onset blindness. Here we show long-term functional rescue using hESC-derived RPE in both the RCS rat and Elov14 mouse, which are animal models of retinal degeneration and Stargardt, respectively." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/22281388", "http://www.ncbi.nlm.nih.gov/pubmed/19521979", "http://www.ncbi.nlm.nih.gov/pubmed/20709808", "http://www.ncbi.nlm.nih.gov/pubmed/22514096", "http://www.ncbi.nlm.nih.gov/pubmed/23601133", "http://www.ncbi.nlm.nih.gov/pubmed/25273541" ]

[]

[ "http://www.disease-ontology.org/api/metadata/DOID:4448", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D008268", "http://www.disease-ontology.org/api/metadata/DOID:10871" ]

[ "The best indication of loxapine is paranoid schizophrenia." ]

[ "schizophrenia" ]

[ "To describe the frequency and trends in the use of antipsychotics for adults with schizophrenia in Canada from 2005 to 2009.", "Antipsychotic recommendations were estimated using CDTI data in which schizophrenia was listed as the indication. RESULTS: First-generation antipsychotic (FGA) recommendations for adults with schizophrenia increased by 38% between 2005 and 2009, from 329 380 to 454 960 recommendations. There were notable increases in recommendations for chlorpromazine, loxapine, zuclopenthixol, and flupentixol.", "Loxapine has been prescribed in France since 1980. Its pharmacological profile is close to that of clozapine: it has dopamine (D2), histamine (H1), serotonin (5-HT2) and adrenergic (alpha 1)-blocking activities. Its best indication seems to be paranoid schizophrenia, although some data suggest bipolar action." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/22014696", "http://www.ncbi.nlm.nih.gov/pubmed/7914051" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D008152", "http://www.biosemantics.org/jochem#4090321", "http://www.biosemantics.org/jochem#4274767", "http://www.biosemantics.org/jochem#4122154" ]

[ "A severe form of this allergy is the Systemic nickel allergy syndrome, clinically characterized by cutaneous manifestions (contact dermatitis, pompholyx, hand dermatitis dyshydrosis, urticaria) with chronic course and systemic symptoms (headache, asthenia, itching, and gastrointestinal disorders related to histopathological alterations of gastrointestinal mucosa, borderline with celiac disease)." ]

[]

[ "patients with \"systemic nickel allergy syndrome\" (SNAS), characterized by Ni-allergic contact dermatitis and systemic reactions after eating Ni-rich food.", "Systemic (gastrointestinal and skin) reactions to ingestion of nickel rich foods in patients with nickel allergic contact dermatitis characterize Systemic Nickel Allergy Syndrome (SNAS)", "Nickel ingested with food can elicit either systemic cutaneous or gastrointestinal symptoms causing a systemic nickel allergy syndrome (SNAS) ", "Sistemic Nickel Allergy Syndrome (SNAS) consisting of urticaria-like troubles, itch, erythema, cutaneous rush, headache, intestinal symptoms, recurrent vesicular palmar dermatitis.", "A severe form of this allergy is the Systemic nickel allergy syndrome, clinically characterized by cutaneous manifestions (contact dermatitis, pompholyx, hand dermatitis dyshydrosis, urticaria) with chronic course and systemic symptoms (headache, asthenia, itching, and gastrointestinal disorders related to histopathological alterations of gastrointestinal mucosa, borderline with celiac disease).", "Some patients with nickel (Ni) allergic contact dermatitis (ACD) suffer from systemic symptoms after ingestion of Ni-rich foods, a condition termed Systemic Nickel Allergy Syndrome (SNAS).", "Recently a Systemic Nickel Allergy Syndrome (SNAS) has been identified in allergic subjects, with a clinical picture of urticaria, general hitching, headache, gastrointestinal troubles. SNAS may affect allergic occupational or non-occupational ones.", "Some patients affected by nickel-contact allergy present digestive symptoms in addition to systemic cutaneous manifestations, falling under the condition known as systemic nickel allergy syndrome (SNAS).", "systemic nickel allergy syndrome (SNAS). The SNAS can have cutaneous signs and symptoms (Systemic Contact Dermatitis or SCD) or extracutaneous signs and symptoms (gastrointestinal, respiratory, neurological, etc.).", "Some patients with nickel (Ni) allergic contact dermatitis suffer from systemic (intestinal or cutaneous) symptoms after ingestion of Ni-rich foods and experience symptoms reduction with low-Ni diet, a condition termed Systemic Ni Allergy Syndrome (SNAS)", "\"systemic nickel allergy syndrome\" (SNAS), characterized by urticaria/angioedema and gastrointestinal symptoms correlated to the ingestion of nickel-containing foods. " ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/22217998", "http://www.ncbi.nlm.nih.gov/pubmed/22652902", "http://www.ncbi.nlm.nih.gov/pubmed/24067467", "http://www.ncbi.nlm.nih.gov/pubmed/24256166", "http://www.ncbi.nlm.nih.gov/pubmed/23405604", "http://www.ncbi.nlm.nih.gov/pubmed/21658331", "http://www.ncbi.nlm.nih.gov/pubmed/23393800", "http://www.ncbi.nlm.nih.gov/pubmed/23527730", "http://www.ncbi.nlm.nih.gov/pubmed/21409856", "http://www.ncbi.nlm.nih.gov/pubmed/20378005", "http://www.ncbi.nlm.nih.gov/pubmed/19843408" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009532", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005512" ]

[ "Riedel thyroiditis (Immunoglobulin G4-related thyroid disease) is caused by IgG4 antibodies. It is part of the spectrum of Ig4-related sclerosing disease.\nIt is associated with fibrosis and inflammation of the thyroid gland." ]

[ "IgG4" ]

[ "LEARNING POINTS: There are potential clinical applications of identifying subsets of patients with IgG4 thyroiditis (FVHT and Riedel thyroiditis).", "The importance of IgG4 in the predictive model of thyroiditis.", "Increased lymphangiogenesis in Riedel thyroiditis (Immunoglobulin G4-related thyroid disease).", "The present study describes in depth a case of Riedel thyroiditis (RT) to clarify its pathogenesis and its putative inclusion in the spectrum of IgG4-related disease. ", "Our findings support the inclusion of RT within the spectrum of IgG4-related thyroid disease (IgG4-RTD). Although the etiology and physiopathology of IgG4-RTD still remain elusive, the results obtained in the present case suggest the participation of lymphatic vessels in the pathogenesis of RT.", "More than 80 % of the left thyroid lobe was effaced by fibrosis and inflammation (lymphocytes, 57 IgG4+ plasma cells per 1 high-power field, an IgG4/IgG ratio of 0.67, and eosinophils) with extension into the surrounding tissues and occlusive phlebitis. ", "Diagnosed early as Riedel disease, the high serum IgG4, immunohistopathology and decreased fibrosis with corticosteroid therapy, finally confirm for the first time, the origin of IgG4-RSD fibrosis of the thyroid.", " While IgG4-RSD is well documented in the pancreas and other organs, it is poorly characterized in the thyroid gland. ", "He was careful to distinguish this from Riedel thyroiditis but it has become clear that fibrosis and atrophy of the thyroid are indeed components of Hashimoto thyroiditis, and in rare cases IgG4-related sclerosing disease may be an outcome. ", "The relationship between HT and Riedel thyroiditis remains unclear; however, recent evidence seems to suggest that it may also be part of the spectrum of Ig4-related sclerosing disease. ", " One patient with advanced thyroid fibrosis associated with Riedel thyroiditis and a history of disease in multiple other organ systems did not have improvement in the thyroid gland, but the disease did not progress to involve new organs. ", "IgG4RD may be present in a certain proportion of patients with a wide variety of diseases, including Mikulicz's disease, autoimmune pancreatitis, hypophysitis, Riedel thyroiditis, interstitial pneumonitis, interstitial nephritis, prostatitis, lymphadenopathy, retroperitoneal fibrosis, inflammatory aortic aneurysm, and inflammatory pseudotumor.", "Increased lymphangiogenesis in Riedel thyroiditis (Immunoglobulin G4-related thyroid disease)", "The present study describes in depth a case of Riedel thyroiditis (RT) to clarify its pathogenesis and its putative inclusion in the spectrum of IgG4-related disease", "The present study describes in depth a case of Riedel thyroiditis (RT) to clarify its pathogenesis and its putative inclusion in the spectrum of IgG4-related disease." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/25011997", "http://www.ncbi.nlm.nih.gov/pubmed/26273473", "http://www.ncbi.nlm.nih.gov/pubmed/22210556", "http://www.ncbi.nlm.nih.gov/pubmed/24783026", "http://www.ncbi.nlm.nih.gov/pubmed/25224542", "http://www.ncbi.nlm.nih.gov/pubmed/21881964", "http://www.ncbi.nlm.nih.gov/pubmed/22498583" ]

[]

[ "http://www.disease-ontology.org/api/metadata/DOID:7188", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013966", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D000906", "http://www.disease-ontology.org/api/metadata/DOID:7166" ]

[ "Depending on the tissue or cell where ILK is ablated we see different effects:\nAblation of ILK in heart results in dilated cardiomyopathy and spontaneous heart failure\nAblation of ILK in fibroblasts leads to impaired healing due to a severe reduction in the number of myofibroblasts\nAblation of ILK in osteoclasts inhibits bone resorption\nAblation of ILK in liver results in enhanced and prolonged cell proliferation and hepatomegaly after phenobarbital administration and in abnormal histology\nAblation of ILK in podocytes caused an aberrant distribution of nephrin and alpha-actinin-4" ]

[ "Ablation of ILK in heart results in dilated cardiomyopathy and spontaneous heart failure", "Ablation of ILK in fibroblasts leads to impaired healing due to a severe reduction in the number of myofibroblasts", "Ablation of ILK in osteoclasts inhibits bone resorption", "Ablation of ILK in liver results in enhanced and prolonged cell proliferation and hepatomegaly after phenobarbital administration and in abnormal histology", "Ablation of ILK in podocytes caused an aberrant distribution of nephrin and alpha-actinin-4" ]

[ "ILK knockdown had no effect on the viability or survival pathway activity pattern of MM cells.", "We conclude that ILK does not play a prominent role in the promotion or sustenance of established MM.", "Defective granulation tissue formation in mice with specific ablation of integrin-linked kinase in fibroblasts", "Here, we show that fibroblast-restricted inactivation of ILK in mice leads to impaired healing due to a severe reduction in the number of myofibroblasts, whereas inflammatory infiltrate and vascularization of the granulation tissue are unaffected.", "in fibroblasts, ILK is crucial for limiting RhoA activity, thus promoting TGFβ1 production, which is essential for dermal repair following injury.", "Our results show that ILK is important for the function, but not the differentiation, of osteoclasts.", "Osteoclast-specific inactivation of the integrin-linked kinase (ILK) inhibits bone resorption.", "ack of ILK in the hepatocytes imparts prolonged proliferative response not only to stimuli related to liver regeneration but also to xenobiotic chemical mitogens, such as PB.", "Liver-specific ablation of integrin-linked kinase in mice results in enhanced and prolonged cell proliferation and hepatomegaly after phenobarbital administration.", "Enhanced liver regeneration following changes induced by hepatocyte-specific genetic ablation of integrin-linked kinase.", "ILK deficiency caused an aberrant distribution of nephrin and alpha-actinin-4 in podocytes, whereas the localization of podocin and synaptopodin remained relatively intact.", "Targeted ablation of ILK from the murine heart results in dilated cardiomyopathy and spontaneous heart failure.", "Here we show that targeted ablation of the integrin-linked kinase (ILK) expression results in spontaneous cardiomyopathy and heart failure by 6 wk of age.", "Together, these results suggest that ILK plays a central role in protecting the mammalian heart against cardiomyopathy and failure.", "Our results show for the first time in vivo the significance of ILK and hepatic ECM-signaling for regulation of hepatocyte proliferation and differentiation.", "Liver-specific ablation of integrin-linked kinase in mice results in abnormal histology, enhanced cell proliferation, and hepatomegaly." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/19575460", "http://www.ncbi.nlm.nih.gov/pubmed/19920070", "http://www.ncbi.nlm.nih.gov/pubmed/16951252", "http://www.ncbi.nlm.nih.gov/pubmed/19349584", "http://www.ncbi.nlm.nih.gov/pubmed/16837631", "http://www.ncbi.nlm.nih.gov/pubmed/20564195", "http://www.ncbi.nlm.nih.gov/pubmed/22658851", "http://www.ncbi.nlm.nih.gov/pubmed/20980390", "http://www.ncbi.nlm.nih.gov/pubmed/18846549" ]

[]

[ "http://www.uniprot.org/uniprot/ILK_MOUSE", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D055011", "http://www.uniprot.org/uniprot/ILK_HUMAN" ]

[ "The d-tubocurarine is a nondepolarizing neuromuscular blocking agent (nondepolarizing muscle relaxant - NDMR). The nondepolarizing muscle relaxants act by blocking the nicotinic acetylcholine receptors of the neuromuscular junction. The neuromuscular blocking action of tubocurarine is reversible and concentration-dependent. The inhibition of acetylcholine-induced currents by d-tubocurarine can be reversed by anticholinesterase agents, such as edrophonium and methamidophos." ]

[ "no" ]

[ "An integrated model describing the interaction of nondepolarizing neuromuscular blocking agents with reversible anticholinesterase agents is derived and compared with a naive model using experimental data obtained from four anesthetized dogs. Three consecutive but separate steady-state d-tubocurarine blocks (approximately 50, 70, and 90%) were induced in each of the four dogs and reversed by short edrophonium infusions.", "The ability of hexamethonium (C6) to reverse the neuromuscular blocking action of tubocurarine (Tc)", "Volatile anesthetics enhance the neuromuscular blockade produced by nondepolarizing muscle relaxants (NDMRs). The neuromuscular junction is a postulated site of this interaction. We tested the hypothesis that volatile anesthetic enhancement of muscle relaxation is the result of combined drug effects on the nicotinic acetylcholine receptor.", "Concentration-effect curves for the inhibition of acetylcholine-induced currents were established for vecuronium, d-tubocurarine, isoflurane, and sevoflurane. Subsequently, inhibitory effects of NDMRs were studied in the presence of the volatile anesthetics at a concentration equivalent to half the concentration producing a 50% inhibition alone. All individually tested compounds produced rapid and readily reversible concentration-dependent inhibition.", "The pharmacological diversity of the different isoforms of the nicotinic acetylcholine receptor arises from the diversity of the subunits that assemble to form the native receptors. The aim of this study was to investigate the actions of the muscle relaxants d-tubocurarine, pancuronium and vecuronium on different isoforms of nicotinic acetylcholine receptors", "At all three receptor types, d-tubocurarine and pancuronium blocked the responses elicited by acetylcholine in a reversible manner. ", "As further evidence of anticholinesterase activity, methamidophos (1-100 microM) was able to reverse the blockade by d-tubocurarine", "There was an initial partial reversal of the neuromuscular inhibition caused by tubocurarine", "Isoflurane and sevoflurane enhance the receptor blocking effects of nondepolarizing muscle relaxants on nicotinic acetylcholine receptors.", "Because other purinergic 2X (P2X) receptor antagonists, NF023 and NF279, do not have the reverse effects on the neuromuscular blockade of d-TC, the effect of NF449 seems irrelevant to inhibition of P2X receptors.", "The association rate constant for Tc binding to sites on the nicotinic acetylcholine receptor appears to be very fast (k+D = 8.9 x 10(8) M-1 s-1) and comparable to that for acetylcholine (ACh).", "The aim of this study was to investigate the mechanism for the reversal effect of NF449 (a suramin analogue) on the neuromuscular block induced by d-tubocurarine (d-TC).", "Study of the reversal effect of NF449 on neuromuscular blockade induced by d-tubocurarine." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/9788777", "http://www.ncbi.nlm.nih.gov/pubmed/16931985", "http://www.ncbi.nlm.nih.gov/pubmed/9291508", "http://www.ncbi.nlm.nih.gov/pubmed/6141831", "http://www.ncbi.nlm.nih.gov/pubmed/2611499", "http://www.ncbi.nlm.nih.gov/pubmed/11867382", "http://www.ncbi.nlm.nih.gov/pubmed/2002334", "http://www.ncbi.nlm.nih.gov/pubmed/11562442", "http://www.ncbi.nlm.nih.gov/pubmed/12145052", "http://www.ncbi.nlm.nih.gov/pubmed/21453711", "http://www.ncbi.nlm.nih.gov/pubmed/2066280", "http://www.ncbi.nlm.nih.gov/pubmed/1884116", "http://www.ncbi.nlm.nih.gov/pubmed/3781972" ]

[]

[ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0015464", "http://www.biosemantics.org/jochem#4273076", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0005892", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011978", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009469", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0031594" ]

[ "Tasimelteon (HETLIOZ™) is an orally bioavailable agonist of the melatonin MT1 and MT2 receptors that has been approved in the US for the treatment of non-24-hour sleep-wake disorder." ]

[ "MT1", "MT2" ]

[ "We present here data on the in vitro binding affinity of tasimelteon for both human melatonin receptors MT1 and MT2, as well as the extended screen of other receptors and enzymes. Results indicate that tasimelteon is a potent Dual Melatonin Receptor Agonist (DMRA) with 2.1-4.4 times greater affinity for the MT2 receptor believed to mediate circadian rhythm phase-shifting (Ki = 0.0692 nM and Ki = 0.17 nM in NIH-3T3 and CHO-K1 cells, respectively), than for the MT1 receptor (Ki = 0.304 nM and Ki = 0.35 nM, respectively).", "The drugs covered target GABAA (zaleplon-CR, lorediplon, EVT-201), orexin (filorexant, MIN-202), histamine-H1 (LY2624803), serotonin 5-HT2A (ITI-007), melatonin/serotonin5-HT1A (piromelatine) and melatonin (indication expansions of prolonged-release melatonin and tasimelteon for pediatric sleep and circadian rhythm disorders) receptors.", "Several melatonin receptors agonists (ramelteon, prolonged-release melatonin, agomelatine and tasimelteon) have recently become available for the treatment of insomnia, depression and circadian rhythms sleep-wake disorders. ", "Tasimelteon (HETLIOZ™) is an orally bioavailable agonist of the melatonin MT1 and MT2 receptors that has been approved in the US for the treatment of non-24-hour sleep-wake disorder. ", "Numerous physiological functions of the pineal gland hormone melatonin are mediated via activation of two G-protein-coupled receptors, MT1 and MT2. The melatonergic drugs on the market, ramelteon and agomelatine, as well as the most advanced drug candidates under clinical evaluation, tasimelteon and TIK-301, are high-affinity nonselective MT1/MT2 agonists. ", "A new melatonin 1 and melatonin 2 agonist tasimelteon improves sleep in these patients, resetting their circadian sleep-wake clocks.", "A general suitability in mitigating other symptoms of major depressive disorder cannot be deduced from the actions of tasimelteon via the melatonin receptors MT1 and MT2.", "Tasimelteon (HETLIOZ™) is an orally bioavailable agonist of the melatonin MT1 and MT2 receptors that has been approved in the US for the treatment of non-24-hour sleep-wake disorder.", "Ramelteon and tasimelteon are new chrono-hypnotic agents, selective for melatonin MT1 and MT2 receptors.", "Results indicate that tasimelteon is a potent Dual Melatonin Receptor Agonist (DMRA) with 2.1-4.4 times greater affinity for the MT2 receptor believed to mediate circadian rhythm phase-shifting (Ki = 0.0692 nM and Ki = 0.17 nM in NIH-3T3 and CHO-K1 cells, respectively), than for the MT1 receptor (Ki = 0.304 nM and Ki = 0.35 nM, respectively). ", "A general suitability in mitigating other symptoms of major depressive disorder cannot be deduced from the actions of tasimelteon via the melatonin receptors MT1 and MT2. ", "We present here data on the in vitro binding affinity of tasimelteon for both human melatonin receptors MT1 and MT2, as well as the extended screen of other receptors and enzymes.", "Results indicate that tasimelteon is a potent Dual Melatonin Receptor Agonist (DMRA) with 2.1-4.4 times greater affinity for the MT2 receptor believed to mediate circadian rhythm phase-shifting (Ki = 0.0692 nM and Ki = 0.17 nM in NIH-3T3 and CHO-K1 cells, respectively), than for the MT1 receptor (Ki = 0.304 nM and Ki = 0.35 nM, respectively).", "We present here data on the in vitro binding affinity of tasimelteon for both human melatonin receptors MT1 and MT2, as well as the extended screen of other receptors and enzymes. Results indicate that tasimelteon is a potent Dual Melatonin Receptor Agonist (DMRA) with 2.1-4.4 times greater affinity for the MT2 receptor believed to mediate circadian rhythm phase-shifting (Ki = 0.0692 nM and Ki = 0.17 nM in NIH-3T3 and CHO-K1 cells, respectively), than for the MT1 receptor (Ki = 0.304 nM and Ki = 0.35 nM, respectively).", "Results indicate that tasimelteon is a potent Dual Melatonin Receptor Agonist (DMRA) with 2.1-4.4 times greater affinity for the MT2 receptor believed to mediate circadian rhythm phase-shifting (Ki = 0.0692 nM and Ki = 0.17 nM in NIH-3T3 and CHO-K1 cells, respectively), than for the MT1 receptor (Ki = 0.304 nM and Ki = 0.35 nM, respectively). Tasimelteon was also shown to have no appreciable affinity for more than 160 other pharmacologically relevant receptors and several enzymes.", " Hetlioz(®) (tasimelteon) is the first approved treatment in the United States for Non-24-Hour Sleep-Wake Disorder (Non-24). We present here data on the in vitro binding affinity of tasimelteon for both human melatonin receptors MT1 and MT2, as well as the extended screen of other receptors and enzymes.", "Results indicate that tasimelteon is a potent Dual Melatonin Receptor Agonist (DMRA) with 2.1-4.4 times greater affinity for the MT2 receptor believed to mediate circadian rhythm phase-shifting (Ki = 0.0692 nM and Ki = 0.17 nM in NIH-3T3 and CHO-K1 cells, respectively), than for the MT1 receptor (Ki = 0.304 nM and Ki = 0.35 nM, respectively).", "We present here data on the in vitro binding affinity of tasimelteon for both human melatonin receptors MT1 and MT2, as well as the extended screen of other receptors and enzymes." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/25423562", "http://www.ncbi.nlm.nih.gov/pubmed/25534555", "http://www.ncbi.nlm.nih.gov/pubmed/24610704", "http://www.ncbi.nlm.nih.gov/pubmed/25207602", "http://www.ncbi.nlm.nih.gov/pubmed/19579175", "http://www.ncbi.nlm.nih.gov/pubmed/24228714", "http://www.ncbi.nlm.nih.gov/pubmed/25422900", "http://www.ncbi.nlm.nih.gov/pubmed/20945020" ]

[]

[]

[ "Yes, zyxin is a focal adhesion protein." ]

[ "yes" ]

[ " zyxin from FAs", "zyxin relocation from focal adhesions ", ". Here we systematically examined the expression, localization, and function of zyxin, a focal adhesion protein", "focal adhesion protein zyxin", "Focal adhesions formed in the absence of α-actinins are delayed in their maturation, exhibit altered morphology, have decreased amounts of Zyxin and VASP, and reduced adhesiveness to extracellular matrix", "one focal adhesion protein (zyxin)", "Zyxin is a focal adhesion protein that has been implicated in the modulation of cell adhesion and motility", " focal adhesion proteins (vinculin, talin, zyxin, FAK, and paxilin)", "Such paxillin-positive complexes mature into focal adhesions by tyrosine phosphorylation and recruitment of zyxin. ", "Zyxin concentrates at focal adhesions ", "zyxin, a focal adhesion protein,", "Focal adhesion proteins Zyxin and Vinculin are co-distributed at tubulobulbar complexes.", " Here we explore the prediction that zyxin, a focal adhesion protein known to be present at podosomes, also is present at apical TBCs", "the association of zyxin with focal adhesions is force-dependent, smaller zyxin-positive adhesion as well as its higher turnover rate suggests that the traction force in focal adhesion on 350 nm topography is decreased.", ". Zyxin is a focal adhesion protein that responds to external mechanical forces;", "Vinculin and zyxin in focal adhesions but not integrins are seen to bridge ligand gaps. ", "The focal adhesion protein zyxin", ". To explore how this response is regulated by focal adhesion-associated proteins the expression levels of paxillin, focal adhesion kinase (FAK), and zyxin were knocked down using gene silencing techniques", " Zyxin is an adaptor protein at focal adhesion plaque", "ocked localization of zyxin at focal adhesion sites" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/22553491", "http://www.ncbi.nlm.nih.gov/pubmed/23454549", "http://www.ncbi.nlm.nih.gov/pubmed/23336069", "http://www.ncbi.nlm.nih.gov/pubmed/19853601", "http://www.ncbi.nlm.nih.gov/pubmed/23742986", "http://www.ncbi.nlm.nih.gov/pubmed/23267329", "http://www.ncbi.nlm.nih.gov/pubmed/22778267", "http://www.ncbi.nlm.nih.gov/pubmed/24039980", "http://www.ncbi.nlm.nih.gov/pubmed/23254340", "http://www.ncbi.nlm.nih.gov/pubmed/21889443", "http://www.ncbi.nlm.nih.gov/pubmed/20139076", "http://www.ncbi.nlm.nih.gov/pubmed/21598955", "http://www.ncbi.nlm.nih.gov/pubmed/22609203", "http://www.ncbi.nlm.nih.gov/pubmed/24157374", "http://www.ncbi.nlm.nih.gov/pubmed/19856213", "http://www.ncbi.nlm.nih.gov/pubmed/20801875", "http://www.ncbi.nlm.nih.gov/pubmed/22516607", "http://www.ncbi.nlm.nih.gov/pubmed/23028903", "http://www.ncbi.nlm.nih.gov/pubmed/23687301", "http://www.ncbi.nlm.nih.gov/pubmed/19173742" ]

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[ "http://www.uniprot.org/uniprot/ZYX_CHICK", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0051894", "http://www.uniprot.org/uniprot/ZYX_HUMAN", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D060589", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0005925", "http://www.uniprot.org/uniprot/ZYX_MOUSE", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0048041", "http://www.uniprot.org/uniprot/ZYX_XENTR", "http://www.uniprot.org/uniprot/ZYX_XENLA", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D022001", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D002448" ]

[ "ELMO proteins are also known to regulate actin cytoskeleton reorganization through activation of the small GTPbinding protein Rac via the ELMO-Dock180 complex. In mammalian cells, ELMO1 interacts with Dock180 as a component of the CrkII/Dock180/Rac pathway responsible for phagocytosis and cell migration. We also show that Hck and ELMO1 interact in intact cells and that ELMO1 is heavily tyrosine-phosphorylated in cells that co-express Hck, suggesting that it is a substrate of Hck.The ELMO1/DOCK180 complex then forms a guanine nucleotide exchange factor for Rac1, regulating its activation during cell migration in different biological systems. Rac activation by the ELMO.Dock180 complex at discrete intracellular locations is mediated by the N-terminal 330 amino acids of ELMO1 rather than generalized Rac activation plays a role in cell migration.", "Engulfment and cell motility 1 (Elmo1) has been reported to cooperate with dedicator of cytokinesis 1 (Dock180) and to be linked to the invasive phenotype of cancer cells through activating small G-protein Rac." ]

[]

[ "Elmo1 helps dock180 to regulate Rac1 activity and cell migration of ovarian cancer", "Engulfment and cell motility 1 (Elmo1) has been reported to cooperate with dedicator of cytokinesis 1 (Dock180) and to be linked to the invasive phenotype of cancer cells through activating small G-protein Rac", "Engulfment and cell motility 1 presents with synergetic action in helping Dock180 to activate Rac1 and promote cell motility, and thus promote untoward expansion and aggressiveness of SOC.", "Elmo1 and Elmo2 are highly homologous cytoplasmic adaptor proteins that interact with Dock family guanine nucleotide exchange factors to promote activation of the small GTPase Rac", "This work provides valuable insights into the molecular regulation of Dock2 by Elmo1 that can be used to design improved inhibitors that target the Elmo-Dock-Rac signaling complex", "Taken together, these findings reveal a previously unknown, nonredundant role for Elmo1 in controlling Dock2 levels and Dock2-dependent T cell migration in primary lymphocytes", "Here we show that CXCL12 stimulation promotes interaction between Gαi2 and ELMO1.", "Gi signalling and ELMO1 are both required for CXCL12-mediated actin polymerization, migration and invasion of breast cancer cells. CXCL12 triggers a Gαi2-dependent membrane translocation of ELMO1, which associates with Dock180 to activate small G-proteins Rac1 and Rac2.", "Our findings indicate that a chemokine-controlled pathway, consisting of Gαi2, ELMO1/Dock180, Rac1 and Rac2, regulates the actin cytoskeleton during breast cancer metastasis.", "These findings suggest that clearance of apoptotic cells in living vertebrates is accomplished by the combined actions of apoptotic cell migration and elmo1-dependent macrophage engulfment.", "Mechanistically, we identified Netrin-1 and its receptor Unc5B as upstream activators of the ELMO1/DOCK180 complex, regulating its functional interaction and leading to Rac1 activation in endothelial cells and vessel formation in zebrafish", "The ELMO1/DOCK180 complex forms a guanine nucleotide exchange factor for Rac1, regulating its activation during cell migration in different biological systems.", "ELMO proteins are also known to regulate actin cytoskeleton reorganization through activation of the small GTPbinding protein Rac via the ELMO-Dock180 complex.", "Finally, in contrast to most other ERM-binding proteins, ELMO1 binding occurred independently of the state of radixin C-terminal phosphorylation, suggesting an ELMO1 interaction with both the active and inactive forms of ERM proteins and implying a possible role of ELMO in localizing or retaining ERM proteins in certain cellular sites. Together these data suggest that ELMO1-mediated cytoskeletal changes may be coordinated with ERM protein crosslinking activity during dynamic cellular functions.", "In mammalian fibroblasts, ELMO1 binds to Dock180, and functions upstream of Rac during phagocytosis and cell migration.", "We previously showed that ELMO1 binds directly to the Hck SH3 domain and is phosphorylated by Hck.", "The data suggest that Src family kinase mediated tyrosine phosphorylation of ELMO1 might represent an important regulatory mechanism that controls signaling through the ELMO1/Crk/Dock180 pathway.", "We also found that ELMO1 regulated multiple Dock180 superfamily members to promote migration.", "This finding suggests that Rac activation by the ELMO.Dock180 complex at discrete intracellular locations mediated by the N-terminal 330 amino acids of ELMO1 rather than generalized Rac activation plays a role in cell migration", "In mammalian cells, ELMO1 interacts with Dock180 as a component of the CrkII/Dock180/Rac pathway responsible for phagocytosis and cell migration.", "The binding of ELMO1 to Hck is specifically dependent on the interaction of a polyproline motif with the SH3 domain of Hck. Our results suggest that these proteins may be novel activators/effectors of Hck.", "We also show that Hck and ELMO1 interact in intact cells and that ELMO1 is heavily tyrosine-phosphorylated in cells that co-express Hck, suggesting that it is a substrate of Hck", "these findings reveal a previously unknown, nonredundant role for Elmo1 in controlling Dock2 levels and Dock2-dependent T cell migration in primary lymphocytes", "Essential role of Elmo1 in Dock2-dependent lymphocyte migration.", "Dock180 and ELMO1 proteins cooperate to promote evolutionarily conserved Rac-dependent cell migration.", "Taken together, these findings reveal a previously unknown, nonredundant role for Elmo1 in controlling Dock2 levels and Dock2-dependent T cell migration in primary lymphocytes. ", "nonredundant role for Elmo1 in controlling Dock2 levels and Dock2-dependent T cell migration in primary lymphocytes.", "Here, we addressed the role of Dock180 and ELMO1 proteins, which function as a complex to mediate Rac activation, in mammalian cell migration.", "Engulfment and cell motility 1 presents with synergetic action in helping Dock180 to activate Rac1 and promote cell motility, and thus promote untoward expansion and aggressiveness of SOC", "Here, we addressed the role of Dock180 and ELMO1 proteins, which function as a complex to mediate Rac activation, in mammalian cell migration", "Here, we addressed the role of Dock180 and ELMO1 proteins, which function as a complex to mediate Rac activation, in mammalian cell migration. ", "This finding suggests that Rac activation by the ELMO.Dock180 complex at discrete intracellular locations mediated by the N-terminal 330 amino acids of ELMO1 rather than generalized Rac activation plays a role in cell migration.", "These studies identify CED-12/ELMO as an upstream regulator of Rac1 that affects engulfment and cell migration from C. elegans to mammals.", "elegans, ced-12 is required for the engulfment of dying cells and for cell migration. In mammalian fibroblasts, ELMO1 binds to Dock180, and functions upstream of Rac during phagocytosis and cell migration." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/11595183", "http://www.ncbi.nlm.nih.gov/pubmed/22503503", "http://www.ncbi.nlm.nih.gov/pubmed/24819662", "http://www.ncbi.nlm.nih.gov/pubmed/23591873", "http://www.ncbi.nlm.nih.gov/pubmed/16377631", "http://www.ncbi.nlm.nih.gov/pubmed/20466982", "http://www.ncbi.nlm.nih.gov/pubmed/12029088", "http://www.ncbi.nlm.nih.gov/pubmed/14638695", "http://www.ncbi.nlm.nih.gov/pubmed/24821968", "http://www.ncbi.nlm.nih.gov/pubmed/15952790" ]

[]

[ "http://www.uniprot.org/uniprot/ELMO1_HUMAN", "http://amigo.geneontology.org/amigo/term/GO:0016477" ]

[ "The proteasome, which identifies and destroys unwanted proteins rapidly, plays a vital role in maintaining cellular protein homeostasis. Proteins that are destined for proteasome-mediated degradation are usually tagged with a chain of ubiquitin linked via lysine (K) 48 that targets them to the proteolytic machinery. K(48)-linked polyubiquitinated proteins are degraded by the proteasomes to elevate cellular levels of amino acids needed for intracellular proliferation. NF-κB and ubiquitylation initially became linked when it was recognised that lysine (K)48-linked ubiquitin chains are involved in the processing of NF-κB precursors and the degradation of inhibitor of kappa B (IκB) proteins." ]

[]

[ "On the LCV, AnkB triggers docking of K(48)-linked polyubiquitinated proteins that are degraded by the host proteasomes to elevate cellular levels of amino acids needed for intracellular proliferation. ", "Transcription and injection of ankB is triggered by attached extracellular bacteria followed by rapid farnesylation and anchoring of AnkB to the cytosolic side of the plasma membrane beneath bacterial attachment, where K(48)-linked polyubiquitinated proteins are assembled and degraded by the proteasomes, leading to a rapid rise in the cellular levels of amino acids.", "Although it has been known for a long time that ubiquitylation has a major role in the activation and regulation of the nuclear factor kappa B (NF-κB) pathway, recent studies have revealed that the picture is a lot more complex than originally thought. NF-κB and ubiquitylation initially became linked when it was recognised that lysine (K)48-linked ubiquitin chains are involved in the processing of NF-κB precursors and the degradation of inhibitor of kappa B (IκB) proteins. ", "The proteasome, which identifies and destroys unwanted proteins rapidly, plays a vital role in maintaining cellular protein homeostasis. Proteins that are destined for proteasome-mediated degradation are usually tagged with a chain of ubiquitin linked via lysine (K) 48 that targets them to the proteolytic machinery. ", "Covalent and reversible post-translational modifications of proteins are a common theme in signaling. Ubiquitin conjugation was originally described to target proteins to proteasomal degradation by ubiquitin polymerization involving lysine (K) 48 residues.", "Proteins tagged with lysine (Lys, K) 48 polyubiquitins chains are destined for degradation by the 26S proteasomal system.", "Ubiquitination is best known for its role in targeting proteins for degradation by the proteasome, but evidence of the nonproteolytic functions of ubiquitin is also rapidly accumulating. One example of the regulatory, rather than proteolytic, function of ubiquitin is provided by study of the tumor necrosis factor (TNF) receptor-associated factor (TRAF) proteins, which function as ubiquitin ligases to synthesize lysine 63 (K(63))-linked polyubiquitin chains to mediate protein kinase activation through a proteasome-independent mechanism.", "Indeed, the TRAF2-interacting protein RIP can mediate IKK activation when it is modified by K(63) polyubiquitin chains, but is targeted to degradation by the proteasome when it is K(48)-polyubiquitinted by the NF-kappaB inhibitor A20.", "NF-κB and ubiquitylation initially became linked when it was recognised that lysine (K)48-linked ubiquitin chains are involved in the processing of NF-κB precursors and the degradation of inhibitor of kappa B (IκB) proteins", "NF-κB and ubiquitylation initially became linked when it was recognised that lysine (K)48-linked ubiquitin chains are involved in the processing of NF-κB precursors and the degradation of inhibitor of kappa B (IκB) proteins", "Proteins that are destined for proteasome-mediated degradation are usually tagged with a chain of ubiquitin linked via lysine (K) 48 that targets them to the proteolytic machinery" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/22389394", "http://www.ncbi.nlm.nih.gov/pubmed/20696248", "http://www.ncbi.nlm.nih.gov/pubmed/19432818", "http://www.ncbi.nlm.nih.gov/pubmed/15728425", "http://www.ncbi.nlm.nih.gov/pubmed/19887490", "http://www.ncbi.nlm.nih.gov/pubmed/24126522" ]

[]

[ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0016567" ]

[ "Yes. It has been demonstrated in a number of experimental studies that DNA (Cytosine-5-)-methyltransferases (DNMT1, DNMT3A and DNMT3B) are deregulated in several types of cancer (invasive cervical cancer, colon cancer, esophageal squamous cell carcinoma (ESCC), gastric cancer, embryonal carcinoma, cervical cancer, adenoma, adenoid cystic carcinoma, salivary gland neoplasms). Moreover, three single nucleotide polymorphisms (SNPs) of the DNMT3B promoter region have been reported to be stratification markers that can predict an individual's susceptibility to cancers. Therefore, DNA (Cytosine-5-)-methyltransferases can serve as tumour markers." ]

[ "yes" ]

[ "Here, we report evidence of the overexpression of DNA methyltransferases 3B (DNMT3B) in invasive cervical cancer and of the inhibition of metastasis by DNMT3B interference.", "This study was designed to determine the significance of DNA methyltransferases (DNMTs) in DNA hypermethylation in esophageal squamous cell carcinoma (ESCC) and to identify DNA methylation markers in serum for the early diagnosis of ESCC.", "DNA methyltransferase 1 as a predictive biomarker and potential therapeutic target for chemotherapy in gastric cancer.", "We examined the prognostic and predictive impact of DNA methyltransferase (DNMT) 1 and 3b expression in gastric carcinomas (GC) treated by neoadjuvant chemotherapy.", "High DNMT1 and DNMT3b expression was found in 105/127 (83%) and 79/127 (62%) carcinomas, respectively.", "Tumoral DNMT3b mRNA up-regulation was significantly correlated with hypermethylation of multiple tumor-related genes (P=0.021).", "A regulator of de novo DNA methyltransferases DNMT3A and DNMT3B, DNMT3L promoter was found to have lost DNA methylation to varying levels in 14 out of 15 cancer cervix samples analysed. The present study highlights the importance of DNA methylation profile at DNMT3L promoter not only as a promising biomarker for cervical cancer, which is the second most common cancer among women worldwide, but also provides insight into the possible role of DNMT3L in cancer development.", "DNMT3L is a novel marker and is essential for the growth of human embryonal carcinoma.", "Among the DNMT genes, we found that mRNA for DNMT3L was specifically expressed in TGCTs, but neither in normal testicular tissues nor in cancer cells of somatic tissue origin. DNMT3L protein was strongly expressed in two EC cell lines, but not in the cell lines of somatic tissue origin.", "Positive nuclear labeling for DNMT3a was found only in few neoplasms: 1 pleomorphic adenoma (9.0%), 2 adenoid cystic carcinoma (16.6%) and 1 mucoepidermoid (9.0%) cases. CONCLUSIONS: Our results were not able to demonstrate a clear correlation between DNMT1 and DNMT3a immunoexpression and salivary gland neoplasms development.", "DNA methylation, mediated by the combined action of three DNA methyltransferases (DNMT1, DNMT3A, and DNMT3B), is essential for mammalian development and is a major contributor to cellular transformation.", "The prevalence, the prognostic effect, and interaction with other molecular markers of DNMT3A mutations was studied in 415 patients with acute myeloid leukemia (AML) younger than 60 years.", "The recent identification of DNMT3A mutations in de novo acute myeloid leukemia prompted us to determine their frequency, patterns and clinical impact in a cohort of 98 patients with either therapy-related or secondary acute myeloid leukemia developing from an antecedent hematologic disorder.", "DNA methyltransferases (DNMT1 and DNMT3b) were also decreased in vorinostat-treated A549 cancer cells.", "To identify the mechanisms responsible for these genome-wide DNA methylation alterations, we measured the gene expression levels of several DNA methyltransferases (DNMTs) and their interacting proteins by TaqMan qPCR and observed increased expression of DNMT3A2, DNMT3B, and EZH2 in tumors.", "DNA methyltransferase 1 (DNMT1) is the primary enzyme that maintains DNA methylation.", "5-Azactydine inhibits cell growth by direct cytotoxic action as well as by inhibition of DNA methyl transferase enzyme.", "Alterations in metabolism of methyl donors, disturbances in activity and/or expression of DNA methyltransferases, and presence of DNA single-strand breaks could contribute to the loss of cytosine methylation during carcinogenesis; however, the precise mechanisms of genomic hypomethylation induced by chemical carcinogens remain largely unknown.", "Recently, three single nucleotide polymorphisms (SNPs) of the DNMT3B promoter region, C46359T (-149C>T), -283T>C, and -579G>T have also been reported to be stratification markers that can predict an individual's susceptibility to cancers.", "Aberrant DNA methylation has been shown to play important roles during multistage carcinogenesis in various human organs.", "Thus, tumour subsets exist that display concurrent decreased BRCA1 expression, BRCA1 promoter methylation, cytoplasmic CTCF expression and with DNMT3b over-expression.", "DNA methylation patterns in genome are maintained during replication by a DNA methyltransferase Dnmt1.", "Aberrant DNA methylation has been shown to play an important role during multistage carcinogenesis in various human organs.", "To investigate the relationship between the expression of DNMT and clinical prognosis in adult patients with acute leukemia (AL), the mRNA expressions of DNMT, p15(INK4B), mdr1 were measured in 72 AL patients and 20 normal controls by semi-quantitative reverse transcription polymerase chain reaction (RT-PCR); the ratio of p15 CpG land methylation was measured in 56 AL patients and 14 normal controls by methylation-specific PCR (MSP-PCR).", "DNA methyltransferase Dnmt1 ensures clonal transmission of lineage-specific DNA methylation patterns in a mammalian genome during replication.", "Overexpression of the major DNA methyltransferase Dnmt1 is cytotoxic and has been hypothesized to result in aberrant hypermethylation of genes required for cell survival.", "DNA (cytosine-5-)-methyltransferase 1 (DNMT1) plays an important role in the maintenance of DNA methylation patterns via complicated networks including signaling pathways and transcriptional factors, relating to cell differentiation or carcinogenesis.", "We evaluated the significance of aberrant DNA methyltransferase 1 (DNMT1) protein expression during gastric carcinogenesis." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/21993668", "http://www.ncbi.nlm.nih.gov/pubmed/22490330", "http://www.ncbi.nlm.nih.gov/pubmed/19468253", "http://www.ncbi.nlm.nih.gov/pubmed/18639561", "http://www.ncbi.nlm.nih.gov/pubmed/15854288", "http://www.ncbi.nlm.nih.gov/pubmed/21045206", "http://www.ncbi.nlm.nih.gov/pubmed/21458988", "http://www.ncbi.nlm.nih.gov/pubmed/15509558", "http://www.ncbi.nlm.nih.gov/pubmed/21629434", "http://www.ncbi.nlm.nih.gov/pubmed/20460473", "http://www.ncbi.nlm.nih.gov/pubmed/19723570", "http://www.ncbi.nlm.nih.gov/pubmed/17071074", "http://www.ncbi.nlm.nih.gov/pubmed/14742272", "http://www.ncbi.nlm.nih.gov/pubmed/17046852", "http://www.ncbi.nlm.nih.gov/pubmed/20613874", "http://www.ncbi.nlm.nih.gov/pubmed/16053511", "http://www.ncbi.nlm.nih.gov/pubmed/1684097", "http://www.ncbi.nlm.nih.gov/pubmed/15499388", "http://www.ncbi.nlm.nih.gov/pubmed/18097598", "http://www.ncbi.nlm.nih.gov/pubmed/21521786", "http://www.ncbi.nlm.nih.gov/pubmed/21150312", "http://www.ncbi.nlm.nih.gov/pubmed/15289832", "http://www.ncbi.nlm.nih.gov/pubmed/23177624", "http://www.ncbi.nlm.nih.gov/pubmed/23251566", "http://www.ncbi.nlm.nih.gov/pubmed/22330137", "http://www.ncbi.nlm.nih.gov/pubmed/17196739", "http://www.ncbi.nlm.nih.gov/pubmed/23100393", "http://www.ncbi.nlm.nih.gov/pubmed/21678477", "http://www.ncbi.nlm.nih.gov/pubmed/20454457", "http://www.ncbi.nlm.nih.gov/pubmed/17965599" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004248" ]

[ "DNA-dependent RNA polymerase II of plant origin transcribes viroid RNA into full-length copies", "DNA-dependent RNA polymerase II purified from healthy plant tissue is capable of synthesizing linear (-)-viroid RNA copies of full length from (+)-viroid RNA templates in vitro. The RNA genome of potato spindle tuber viroid (PSTV) is transcribed in vitro into complementary DNA and RNA by DNA-dependent DNA polymerase I and RNA polymerase, respectively, from Escherichia coli. Host DNA-dependent RNA polymerase II (RNAP II) was proposed to be critical for its replication, but no interaction site for RNAP II on the PSTVd RNA genome was identified. Whereas maximum total activity was observed in 1 mM Mn(2+) with a pronounced reduction (80%) in 5 mM Mn(2+), CEV synthesis was maintained in 1-15 mM Mn(2+).", "DNA-dependent RNA polymerase II purified from healthy plant tissue is capable of synthesizing linear (-)-viroid RNA copies of full length from (+)-viroid RNA templates in vitro. Research results support a role for RNA polymerase II in viroid replication and provide the first direct evidence of an association in vivo between host RNA polymerase II and CEV." ]

[ "DNA-dependent RNA polymerase II", "RNA polymerase II", "RNAP II" ]

[ "DNA-dependent RNA polymerase II of plant origin transcribes viroid RNA into full-length copies", "DNA-dependent RNA polymerase II purified from healthy plant tissue is capable of synthesizing linear (-)-viroid RNA copies of full length from (+)-viroid RNA templates in vitro.", "Viroid RNA is accepted as a template for in vitro transcription by DNA-dependent DNA polymerase I and RNA polymerase from Escherichia coli", "The RNA genome of potato spindle tuber viroid (PSTV) is transcribed in vitro into complementary DNA and RNA by DNA-dependent DNA polymerase I and RNA polymerase, respectively, from Escherichia coli.", "In vitro transcription of viroid RNA into full-length copies by RNA-dependent RNA polymerase from healthy tomato leaf tissue", "RNA-dependent RNA polymerase from healthy tomato plant tissue accepts potato spindle tuber viroid (PSTV) RNA as a template for the in vitro synthesis of full-length RNA copies of the PSTV genome", "Whereas maximum total activity was observed in 1 mM Mn(2+) with a pronounced reduction (80%) in 5 mM Mn(2+), CEV synthesis was maintained in 1-15 mM Mn(2+). Inhibition of alpha-amanitin-sensitive CEV synthesis in 200 mM (NH(4))(2)SO(4) resembles the reaction of RNA polymerase II on a free nucleic acid template", "Citrus exocortis viroid RNA is associated with the largest subunit of RNA polymerase II in tomato in vivo.", "The results support a role for RNA polymerase II in viroid replication and provide the first direct evidence of an association in vivo between host RNA polymerase II and CEV.", "Transcription of potato spindle tuber viroid by RNA polymerase II starts predominantly at two specific sites", "Pospiviroidae, with their main representative potato spindle tuber viroid (PSTVd), are replicated via a rolling circle mechanism by the host-encoded DNA-dependent RNA polymerase II (pol II)", "Transcription of potato spindle tuber viroid by RNA polymerase II starts in the left terminal loop", "Viroids of the family Pospiviroidae, of which potato spindle tuber viroid (PSTVd) is the type strain, are replicated by the host's DNA-dependent RNA polymerase II in the nucleus.", "Tomato RNA polymerase II interacts with the rod-like conformation of the left terminal domain of the potato spindle tuber viroid positive RNA genome", "Host DNA-dependent RNA polymerase II (RNAP II) was proposed to be critical for its replication, but no interaction site for RNAP II on the PSTVd RNA genome was identified. ", "RNA polymerase II is implicated in the RNA-templated RNA synthesis during replication of viroids and Hepatitis Delta Virus (HDV); however, neither the RNA template nor protein factor requirements for this process are well defined.", "Viroids of the Pospiviroidae family, as represented by the Potato spindle tuber viroid (PSTVd), replicate in the nucleus by utilizing DNA-dependent RNA polymerase II.", "The results support a role for RNA polymerase II in viroid replication and provide the first direct evidence of an association in vivo between host RNA polymerase II and CEV.", "These results suggest that either RNA polymerase I or an unidentified RNA polymerase activity resistant to alpha-amanitin, acting on an RNA template, plays a role in the replication of ASBV, whereas for the rest of the viroids studied so far it appears that RNA polymerase II is involved", "RNA polymerase II is implicated in the RNA-templated RNA synthesis during replication of viroids and Hepatitis Delta Virus (HDV); however, neither the RNA template nor protein factor requirements for this process are well defined", "Viroids of the family Pospiviroidae, of which potato spindle tuber viroid (PSTVd) is the type strain, are replicated by the host&apos;s DNA-dependent RNA polymerase II in the nucleus", "Viroids of the Pospiviroidae family, as represented by the Potato spindle tuber viroid (PSTVd), replicate in the nucleus by utilizing DNA-dependent RNA polymerase II. ", "These results suggest that either RNA polymerase I or an unidentified RNA polymerase activity resistant to alpha-amanitin, acting on an RNA template, plays a role in the replication of ASBV, whereas for the rest of the viroids studied so far it appears that RNA polymerase II is involved. ", "Inhibition studies with alpha-amanitin showed that the synthesis of ASBV-specific RNAs was not affected by concentrations of 1 and 200 micrograms/ml of the drug, which typically inhibit RNA polymerase II and III, respectively, from most animal and plant systems. These results suggest that either RNA polymerase I or an unidentified RNA polymerase activity resistant to alpha-amanitin, acting on an RNA template, plays a role in the replication of ASBV, whereas for the rest of the viroids studied so far it appears that RNA polymerase II is involved.", "Nucleoprotein complexes in the soluble fraction which bound to a monoclonal antibody to the carboxy terminal domain of the largest subunit of RNA polymerase II (8WG16) were affinity purified and contained plus- and minus-sense CEV RNA. The results support a role for RNA polymerase II in viroid replication and provide the first direct evidence of an association in vivo between host RNA polymerase II and CEV." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/11713308", "http://www.ncbi.nlm.nih.gov/pubmed/6896006", "http://www.ncbi.nlm.nih.gov/pubmed/1733098", "http://www.ncbi.nlm.nih.gov/pubmed/10664390", "http://www.ncbi.nlm.nih.gov/pubmed/10668797", "http://www.ncbi.nlm.nih.gov/pubmed/6760914", "http://www.ncbi.nlm.nih.gov/pubmed/16912306", "http://www.ncbi.nlm.nih.gov/pubmed/22422064", "http://www.ncbi.nlm.nih.gov/pubmed/7231549", "http://www.ncbi.nlm.nih.gov/pubmed/16593489", "http://www.ncbi.nlm.nih.gov/pubmed/16406459" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012313", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D014772" ]

[ "HSP90\nCDC37\nGRP75\nHSP60\nLRPPRC\nTUFM\nPICK1\nPSMA7\nPael receptor" ]

[ "HSP90", "CDC37", "GRP75", "HSP60", "LRPPRC", "TUFM", "PICK1", "PSMA7", "XAPC7", "Pael receptor" ]

[ "In addition to two known binding partners (HSP90, CDC37), 12 proteins were identified using the TAP assay; four of which are mitochondrially localized (GRP75, HSP60, LRPPRC, and TUFM).", "We find that parkin binds PICK1 via a PDZ-mediated interaction, which predominantly promotes PICK1 monoubiquitination rather than polyubiquitination. ", "We have identified the 20S proteasomal subunit alpha4 (synonyms: PSMA7, XAPC7, subunit alpha type 7) as a new interacting partner of parkin.", "we cloned parkin-binding protein using a yeast two-hybrid system and identified a putative G protein-coupled receptor protein,which we named the Pael receptor (Pael-R)", ", whose interactions with CASK are reviewed here, include the Parkinson's disease molecule parkin, " ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/21437181", "http://www.ncbi.nlm.nih.gov/pubmed/20064468", "http://www.ncbi.nlm.nih.gov/pubmed/18623069", "http://www.ncbi.nlm.nih.gov/pubmed/24244333", "http://www.ncbi.nlm.nih.gov/pubmed/15987638", "http://www.ncbi.nlm.nih.gov/pubmed/14579121", "http://www.ncbi.nlm.nih.gov/pubmed/17553932", "http://www.ncbi.nlm.nih.gov/pubmed/17229476", "http://www.ncbi.nlm.nih.gov/pubmed/18190519", "http://www.ncbi.nlm.nih.gov/pubmed/16842202", "http://www.ncbi.nlm.nih.gov/pubmed/16714300" ]

[]

[ "http://www.uniprot.org/uniprot/PRKN2_HUMAN" ]

[ "Riociguat is generic name of drug Adempas. It is a soluble guanylate cyclase stimulator that was approved for the treatment of patients with chronic thromboembolic pulmonary hypertension and pulmonary arterial hypertension." ]

[ "riociguat" ]

[ "Riociguat (adempas): a novel agent for the treatment of pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension.", "Riociguat (Adempas): a novel agent for the treatment of pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension.", "Riociguat (Adempas(®)), a soluble guanylate cyclase stimulator, is a new, first-in-class drug approved for the treatment of patients with chronic thromboembolic pulmonary hypertension (CTEPH) [inoperable or persistent/recurrent following surgery] or pulmonary arterial hypertension (PAH). ", "On October 8, 2013, riociguat (Adempas®) became the first medication approved for multiple etiologies of PH.", "Duavee, an oral contraceptive; riociguat (Adempas) for two types of pulmonary hypertension; and macitentan (Opsumit) for pulmonary arterial hypertension.", "Riociguat (Adempas(®)), an oral first-in-class soluble guanylate cyclase (sGC) stimulator, is under global development by Bayer Healthcare Pharmaceuticals Inc. for the treatment of adult patients with inoperable or chronic/persistent chronic thromboembolic pulmonary hypertension (CTEPH) and for the treatment of adult patients with pulmonary arterial hypertension (PAH). ", "Riociguat (Adempas): a novel agent for the treatment of pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension", "Riociguat (Adempas(®)), an oral first-in-class soluble guanylate cyclase (sGC) stimulator, is under global development by Bayer Healthcare Pharmaceuticals Inc", "Duavee, an oral contraceptive; riociguat (Adempas) for two types of pulmonary hypertension; and macitentan (Opsumit) for pulmonary arterial hypertension" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/24218053", "http://www.ncbi.nlm.nih.gov/pubmed/25395817", "http://www.ncbi.nlm.nih.gov/pubmed/25352393", "http://www.ncbi.nlm.nih.gov/pubmed/24391396", "http://www.ncbi.nlm.nih.gov/pubmed/24524094" ]

[]

[]

[ "Staphylococcus epidermis, including methicillin-resistant strains, are inhibited by vancomycin concentrations of 1-4 µg/ml. \nStaphylococcus pyogenes, Streptococcus pneumonia, and Streptococcus viridans are susceptible to 2 µg/ml vancomycin. \nBacillus spp. are inhibited by 2 µg/ml, Corynebacterium spp. by 0.04-3.1 µg/ml and Clostridium spp. by 0.39-6 µg/ml vancomycin. \nPeak and trough concentrations of vancomycin should be 40 μg/ml and 10 μg/ml, respectively, to both be effective and avoid oto- or nephrotoxicity in adults. There is no ideal pattern of vancomycin dosing; vancomycin dosages must be individualized. Because vancomycin activity is primarily time-dependent, the 24-h area under the curve (AUC0-24h) divided by the minimum inhibitor concentration (MIC) value (AUC0-24h/MIC) is a better predictor of efficacy. In adults with MIC values less than 1 μg/ml, trough concentrations greater than 10 µg/ml result in AUC0-24h/MIC values 400\nCompared with adults, neonates have a higher extracellular fluid volume and a limited renal elimination capacity resulting in different pharmacokinetics subject to maturation stage. Infants weighing less than 1,000 gm had significantly larger volumes of drug distribution and consequently longer drug half-lives than larger premature infants, regardless of postconceptual or actual age. These differences alter the vancomycin dosing recommendations in these two groups of premature infants.\nVancomycin-associated nephrotoxicity is rare in neonates, even with serum peak concentrations 40 microg/mL. Vancomycin is associated with ototoxicity.\nThere is no consensus on vancomycin dosing in newborns and young infants, which leads to significant variation in vancomycin dosing regimens and TDM guidance across neonatal units. The development of standardized, evidence-based protocols should be prioritized." ]

[]

[ "Monte Carlo simulations based on our population pharmacokinetic model suggest that vancomycin dosing guidelines based on serum creatinine concentration have a greater likelihood of achieving trough concentrations in the 5-15-mg/L range compared with other evaluated dosing regimens. None of the four dosing regimens is suitable to produce target trough concentration of 15-20 mg/L in an acceptable number of patients.", "There is significant variation in gentamicin and vancomycin dosing regimens and TDM guidance across a UK network of neonatal units. The development of standardized, evidence-based protocols should be prioritized.", "Vancomycin, by contrast, was associated with ototoxicity.", "There is no consensus on vancomycin dosing in newborns and young infants.", "The modified regimen for a target vancomycin concentration of 25 mg/l consisted of a bolus of 20 mg/kg followed by continuous infusion of 30 mg/kg.", "There is no ideal pattern of vancomycin dosing; vancomycin dosages must be individualized.", "Recommended vancomycin schedules for term newborn infants with neonatal sepsis should be based on the weight and postconceptual age only to start antimicrobial therapy. There is", "Targets were a trough concentration between 5 and 15 mg/L and a peak below 40 mg/L. In the prospective study, the optimal scheme was tested in 22 patients. RESULTS: Of the 108 patients, 34.3% of measured trough concentrations and 17.6% of peak concentrations were outside the desired therapeutic range. The model that best fitted the data included clearance and volume per kilogram and was independent of gestational age. Simulation of various dosing schemes showed that a dosing schedule of 30 mg/kg/day, irrespective of gestational age, in three doses was optimal, and this scheme was prospectively tested. Mean trough concentrations before the second dose were 8.2 +/- 2.2 mg/L versus a predicted trough of 8.9 +/- 2.5 mg/L. No peak levels higher than 40 mg/L were found. CONCLUSIONS: The use of the proposed schedule leads to adequate vancomycin trough serum concentrations, and there is no need for routine monitoring of peak serum concentrations.", "Vancomycin-associated nephrotoxicity is rare in neonates, even with serum peak concentrations >40 microg/mL.", "Infants weighing less than 1,000 gm had significantly larger volumes of drug distribution and consequently longer drug half-lives than larger premature infants, regardless of postconceptual or actual age. These differences alter the vancomycin dosing recommendations in these two groups of premature infants. We recommend initial dosage regimens consisting of a loading dose of vancomycin of 25 mg/kg followed by doses of 15 mg/kg every 12 hours for infants with weights less than 1,000 gm. Infants weighing over 1,000 gm should receive 10 mg/kg every 12 hours, with a loading dose of 12.5 mg/kg. Serum vancomycin concentration should be monitored, however, for final optimization of therapy." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/21862473", "http://www.ncbi.nlm.nih.gov/pubmed/22488303", "http://www.ncbi.nlm.nih.gov/pubmed/3991250", "http://www.ncbi.nlm.nih.gov/pubmed/11378679", "http://www.ncbi.nlm.nih.gov/pubmed/21455009", "http://www.ncbi.nlm.nih.gov/pubmed/10801244", "http://www.ncbi.nlm.nih.gov/pubmed/2630235", "http://www.ncbi.nlm.nih.gov/pubmed/21378399", "http://www.ncbi.nlm.nih.gov/pubmed/10103340", "http://www.ncbi.nlm.nih.gov/pubmed/22892931" ]

[]

[ "http://www.biosemantics.org/jochem#4272288", "http://www.biosemantics.org/jochem#4272290", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D014640", "http://www.biosemantics.org/jochem#4022642", "http://www.biosemantics.org/jochem#4145076", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D007231", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D007234" ]

[ "Single guide RNA is part of the CRISPR/Cas9 system." ]

[ "Single guide RNA is part of the CRISPR/Cas9 system." ]

[ "Cas9, an RNA-guided DNA endonuclease found in clustered regularly interspaced short palindromic repeats (CRISPR) bacterial immune systems, is a versatile tool for genome editing, transcriptional regulation, and cellular imaging applications. Structures of Streptococcus pyogenes Cas9 alone or bound to single-guide RNA (sgRNA) and target DNA revealed a bilobed protein architecture that undergoes major conformational changes upon guide RNA and DNA binding.", "Although the lobes do not interact on their own, the sgRNA recruits them into a ternary complex that recapitulates the activity of full-length Cas9 and catalyzes site-specific DNA cleavage. The use of a modified sgRNA abrogates split-Cas9 activity by preventing dimerization, allowing for the development of an inducible dimerization system. ", "This new type of genetic library is constructed through the lentiviral delivery of single-guide RNA collections that direct Cas9 or inactive dead Cas9 fused with effectors to interrogate gene function or regulate gene transcription in targeted cells. ", "The CRISPR/Cas9 system has recently emerged as a powerful tool for functional genomic studies in Drosophila melanogaster. However, single-guide RNA (sgRNA) parameters affecting the specificity and efficiency of the system in flies are still not clear. Here, we found that off-target effects did not occur in regions of genomic DNA with three or more nucleotide mismatches to sgRNAs.", "Our work demonstrates a comprehensive optimization of sgRNA and promises to vastly simplify CRISPR/Cas9 experiments in Drosophila.", "Targeted genome engineering is expected to contribute significantly to future varietal improvement, and genome editing technologies using zinc finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs), and clustered regularly interspaced short palindromic repeat (CRISPR)/Cas9/single guide RNA (sgRNA) have already been successfully used to genetically modify plants.", "A unique capability of the CRISPR/Cas9 system is multiplex genome engineering by delivering a single Cas9 enzyme and two or more single guide RNAs (sgRNAs) targeted to distinct genomic sites.", "To determine if the Cas9 and single guide RNA (sgRNA) genes were functional in C. reinhardtii, we tested the ability of a codon-optimized Cas9 gene along with one of four different sgRNAs to cause targeted gene disruption during a 24-h period immediately following transformation.", "Recently, compared to the wildtype nuclease, paired Cas9 nickase (Cas9n) combined with single guide RNA (sgRNA) molecules has been found to enhance the specificity of genome editing while reducing off-target effects.", "Here we utilized a CRISPR/CAS9-based system with single guide RNAs to disrupt genes in T. gondii.", "To address the need for uniform and sustained delivery of multiplex CRISPR/Cas9-based genome engineering tools, we developed a single lentiviral system to express a Cas9 variant, a reporter gene and up to four sgRNAs from independent RNA polymerase III promoters that are incorporated into the vector by a convenient Golden Gate cloning method.", "A unique capability of the CRISPR/Cas9 system is multiplex genome engineering by delivering a single Cas9 enzyme and two or more single guide RNAs (sgRNAs) targeted to distinct genomic sites. ", "Using synthetic single RNA guides, Cas9 can be reprogrammed to create specific double-stranded DNA breaks in the genomes of a variety of organisms, ranging from human cells to bacteria, and thus constitutes a powerful tool for genetic engineering. " ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/25122746", "http://www.ncbi.nlm.nih.gov/pubmed/25048165", "http://www.ncbi.nlm.nih.gov/pubmed/25731961", "http://www.ncbi.nlm.nih.gov/pubmed/24870050", "http://www.ncbi.nlm.nih.gov/pubmed/23907171", "http://www.ncbi.nlm.nih.gov/pubmed/25713377", "http://www.ncbi.nlm.nih.gov/pubmed/24838573", "http://www.ncbi.nlm.nih.gov/pubmed/24825012", "http://www.ncbi.nlm.nih.gov/pubmed/25398342", "http://www.ncbi.nlm.nih.gov/pubmed/25437567", "http://www.ncbi.nlm.nih.gov/pubmed/25274302", "http://www.ncbi.nlm.nih.gov/pubmed/25161872", "http://www.ncbi.nlm.nih.gov/pubmed/24710347", "http://www.ncbi.nlm.nih.gov/pubmed/24920971", "http://www.ncbi.nlm.nih.gov/pubmed/25239977" ]

[]

[ "http://www.uniprot.org/uniprot/CAS9_NEIMA", "http://www.uniprot.org/uniprot/CAS9_CAMJE", "http://www.uniprot.org/uniprot/CAS9_FRATN", "http://www.uniprot.org/uniprot/CAS9_STRTR", "http://www.uniprot.org/uniprot/CAS9_ACTNH", "http://www.uniprot.org/uniprot/CAS9_NEIM8", "http://www.uniprot.org/uniprot/CAS9_PASMU" ]

[ "Idelalisib represents a first-in-class specific inhibitor of the phosphoinositol-3 kinase (PI3K) delta isoform." ]

[ "PI3K-δ", "phosphoinositol-3 kinase delta isoform" ]

[ " PI3Kδ (idelalisib). ", "Idelalisib (PI3K inhibitor) ", "In the last few years, several classes of potent and selective small molecule PI3K inhibitors have been developed, and at least fifteen compounds have progressed into clinical trials as new anticancer drugs. Among these, idelalisib", " idelalisib represents a first-in-class specific inhibitor of the phosphoinositol-3 kinase (PI3K) delta isoform.", "PI3K inhibitor idelalisib ", "the PI3K inhibitor idelalisib ", "PI3K-δ inhibitor idelalisib", "idelalisib (GS-1101) -a specific isoform of the PI3K (PI3K) inhibitor." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/24261963", "http://www.ncbi.nlm.nih.gov/pubmed/24009233", "http://www.ncbi.nlm.nih.gov/pubmed/24085367", "http://www.ncbi.nlm.nih.gov/pubmed/23847354", "http://www.ncbi.nlm.nih.gov/pubmed/24323900", "http://www.ncbi.nlm.nih.gov/pubmed/24014301", "http://www.ncbi.nlm.nih.gov/pubmed/23617253", "http://www.ncbi.nlm.nih.gov/pubmed/24273091", "http://www.ncbi.nlm.nih.gov/pubmed/24060900" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011955", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004364" ]

[ "Phenytoin is not used in pregnancy as it is associated with a severe fetal deformation. From the other anticonvulsants most studies report the higher association between use during pregnancy and spin bifida to occur with Valproate." ]

[ "Valproate" ]

[ "The teratogenicity of antiepilepsy drug valproic acid (VPA) mostly is found in genetic and somatic levels, causing teratogenesis involving neurotubular defects (NTDs), anencephaly, lumbosacral meningomyelocele, and leg dysfunction due to spina bifida aperta.", "The summary odds ratio estimate for the association between valproic acid and spina bifida was 11.9 (95% uncertainty interval (UI): 4.0-21.2); for valproic acid and cleft palate 5.8 (95% UI: 3.3-9.5); for carbamazepine and spina bifida 3.6 (95% UI: 1.3-7.8); and for carbamazepine and cleft palate 2.4 (95% UI: 1.1-4.5) in the United States.", "Increased risk for MCMs could be demonstrated only for exposure to valproate (5.6%, p = 0.005) and AED polytherapy (6.1%, p = 0.02). Neonatal spina bifida was not significantly increased, but was a major indication for elective pregnancy termination among women with epilepsy. ", "Valproic acid, a drug commonly used to treat seizures and other psychiatric disorders, causes neural tube defects (NTDs) in exposed fetuses at a rate 20 times higher than in the general population. Failure of the neural tube to close during development results in exencephaly or anencephaly, as well as spina bifida.", "Associations were found for spina bifida with valproic acid. ", "Fetal exposure to valproic acid or carbamazepine increases the risk of neural tube defect (NTD)", "Women with epilepsy giving birth during 1973 to 1991 were identified by record linkage of Swedish health registries. Among 3,625 identified infants, 9 had spina bifida. A nested case-control study was performed, comparing drugs used in early pregnancy in the 9 cases and in 18 controls, matched for year of delivery, maternal age, and parity. Six of the spina bifida mothers had used carbamazepine and two had used valproic acid. Among the controls, 5 women used carbamazepine and one valproic acid. There is an apparent excess risk for spina bifida after use of either of these two drugs, but it is not statistically significant when the analysis is restricted to drug-using women. T", "A significant association was seen between maternal use of valproic acid and spina bifida, and a weaker, non-significant one between carbamazepine and spina bifida.", "A statistically significant association between Spina Bifida and Valproic Acid (odds ratio 22.7; Fisher p value = 0.0364) was observed: no other anticonvulsant tested showed any association with any type of malformation." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/10339792", "http://www.ncbi.nlm.nih.gov/pubmed/3939491", "http://www.ncbi.nlm.nih.gov/pubmed/21766433", "http://www.ncbi.nlm.nih.gov/pubmed/8075508", "http://www.ncbi.nlm.nih.gov/pubmed/23082254", "http://www.ncbi.nlm.nih.gov/pubmed/22051200", "http://www.ncbi.nlm.nih.gov/pubmed/17075842", "http://www.ncbi.nlm.nih.gov/pubmed/19490036", "http://www.ncbi.nlm.nih.gov/pubmed/11077457", "http://www.ncbi.nlm.nih.gov/pubmed/2707392" ]

[]

[ "http://www.disease-ontology.org/api/metadata/DOID:0080016", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D000927" ]

[ "Yersinia pestis is the causative bacteria of the plague." ]

[ "Yersinia pestis" ]

[ " the causative bacteria Yersinia pestis as an agent of biological warfare have highlighted the need for a safe, efficacious, and rapidly producible vaccine. ", "Yersinia, the causative bacteria of the bubonic plague and other enteric diseases" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/8052312", "http://www.ncbi.nlm.nih.gov/pubmed/16410352" ]

[]

[]

[ "The 1,4-benzothiazepine derivative JTV-519 is a new type of calcium ion channel modulator.JTV-519, which has potential use as an antiarrhythmic [285800]. The drug is a novel cardioprotectant derivative of 1,4-benzothiazepine for which phase I trials were completed in the third quarter of 1998", "JTV519 (K201), is a 1,4-benzothiazepine derivative and multi-channel blocker, which has been found to stabilize RyR2s and decrease SR Ca²⁺ leak." ]

[ "1,4-benzothiazepine", "benzothiazepine" ]

[ "In these conditions, JTV519 (K201), a 1,4-benzothiazepine derivative and multi-channel blocker, stabilizes RyR2s and decrease SR Ca²⁺ leak.", "The 1,4-benzothiazepine derivative JTV519, and the more specific derivative S107 (2,3,4,5,-tetrahydro-7-methoxy-4-methyl-1,4-benzothiazepine), are thought to improve skeletal muscle function by stabilizing the RyR1-FKBP12 complex.", "In this article, we synthesize derivatives of the channel activator 4-chloro-3-methyl phenol (4-CmC) and the 1,4-benzothiazepine channel inhibitor 4-[-3{1-(4-benzyl) piperidinyl}propionyl]-7-methoxy-2,3,4,5-tetrahydro-1,4-benzothiazepine (K201, JTV519) with enhanced electron donor properties.", "K201 (JTV519), a benzothiazepine derivative, has been shown to possess anti-arrhythmic and cardioprotective properties, but the mechanism of its action is both complex and controversial.", "K201 (JTV519) is a 1,4-benzothiazepine derivative that exhibits a strong cardioprotective action and acts as a multiple-channel blocker, including as a K+ channel blocker.", "A derivative of 1,4-benzothiazepine (JTV519) increased the affinity of calstabin2 for RyR2, which stabilized the closed state of RyR2 and prevented the Ca2+ leak that triggers arrhythmias.", "We report that a new drug, the 1,4-benzothiazepine derivative JTV519, reverses this pathogenic process. JTV519 is known to have a protective effect against Ca2+ overload-induced myocardial injury.", "In conclusion, JTV519, a new 1,4-benzothiazepine derivative, corrected the defective channel gating in RyR (increase in both the rapid conformational change and the subsequent Ca(2+) release rate) in HF.", "A newly synthesized 1,4-benzothiazipine derivate, 4-[3-(4-benzylpiperidin-1-yl) propionyl]-7-methoxy-2,3,4,5-tetrahydro-1, 4-benzothiazepine monohydrochloride (JTV-519) was examined for its ability to reverse P-glycoprotein (P-gp) and multidrug resistance protein 1 (MRP1) mediated multidrug resistance (MDR) in K562/MDR and KB/MRP cells, respectively. ", "JTV-519, which has potential use as an antiarrhythmic [285800]. The drug is a novel cardioprotectant derivative of 1,4-benzothiazepine for which phase I trials were completed in the third quarter of 1998", "The 1,4-benzothiazepine derivative JTV-519 is a new type of calcium ion channel modulator.", "A new 1,4-benzothiazepine derivative, JTV519 (JTV), has strong protective effects against isoproterenol-induced myocardial injury. ", "A newly synthesized benzothiazepine derivative, JTV-519 (JT) has been reported to be cardioprotective.", "Protective effect of JTV519, a new 1,4-benzothiazepine derivative, on prolonged myocardial preservation", "A new 1,4-benzothiazepine derivative, JTV519, has a strong protective effect against Ca(2+) overload-induced myocardial injury.", " We report that a new drug, the 1,4-benzothiazepine derivative JTV519, reverses this pathogenic process.", "Protective effect of JTV519, a new 1,4-benzothiazepine derivative, on prolonged myocardial preservation.", "A new 1,4-benzothiazepine derivative, JTV519 (JTV), has strong protective effects against isoproterenol-induced myocardial injury.", "A new 1,4-benzothiazepine derivative, JTV519, has a strong protective effect against Ca(2+) overload-induced myocardial injury.", " In these conditions, JTV519 (K201), a 1,4-benzothiazepine derivative and multi-channel blocker, stabilizes RyR2s and decrease SR Ca?⁺ leak.", "The cardioprotective effects of a new 1,4-benzothiazepine derivative, JTV519, on ischemia/reperfusion-induced Ca2+ overload in isolated rat hearts.", "We report that a new drug, the 1,4-benzothiazepine derivative JTV519, reverses this pathogenic process" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/11429046", "http://www.ncbi.nlm.nih.gov/pubmed/11757794", "http://www.ncbi.nlm.nih.gov/pubmed/21989257", "http://www.ncbi.nlm.nih.gov/pubmed/10683355", "http://www.ncbi.nlm.nih.gov/pubmed/15073377", "http://www.ncbi.nlm.nih.gov/pubmed/12433661", "http://www.ncbi.nlm.nih.gov/pubmed/23349825", "http://www.ncbi.nlm.nih.gov/pubmed/17112502", "http://www.ncbi.nlm.nih.gov/pubmed/22509897", "http://www.ncbi.nlm.nih.gov/pubmed/10789707", "http://www.ncbi.nlm.nih.gov/pubmed/12551874", "http://www.ncbi.nlm.nih.gov/pubmed/12359358", "http://www.ncbi.nlm.nih.gov/pubmed/17313373", "http://www.ncbi.nlm.nih.gov/pubmed/10864882", "http://www.ncbi.nlm.nih.gov/pubmed/11101196" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=chemicals_and_drugs_category", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004339" ]

[ "Malat-1 expression is upregulated in several tumor types" ]

[ "upregulated" ]

[ "lncRNA MALAT-1 expression is upregulated in some tumors.", "Metastasis-Associated-in-Lung-Adenocarcinoma-Transcript-1 (MALAT-1) is an ncRNA that is highly expressed in several tumor types", "metastasis-associated lung adenocarcinoma transcript (MALAT)-1 is known to be consistently upregulated in several epithelial malignancies", "MALAT-1 was up-regulated in human prostate cancer tissues and cell lines.", "Genome-wide profiling revealed that MALAT-1 and prostate cancer gene 3 (PCA3) are overexpressed in PCa tissues", "The level of MALAT-1 in LSCC was significantly higher than that in the corresponding adjacent non-neoplastic tissues", "metastasis-associated lung adenocarcinoma transcript 1, MALAT1, is a long non-coding RNA (lncRNA) that has been discovered as a marker for lung cancer metastasis. It is highly abundant,", "(MALAT1), a long non-coding RNA (lncRNA), is up-regulated in many solid tumors and associated with cancer metastasis and recurrence", " Quantitative analyses indicated a 6-7-fold increased RNA level in HCCs versus uninvolved liver,", "(hcn), encoding a 7-kb mRNA-like transcript. The gene appears to be the murine ortholog of the human alpha gene, that is, MALAT-1.", "After suppression subtractive hybridization and differential screening, we detected the metastasis-associated lung adenocarcinoma transcript 1 (MALAT-1) gene as one of the major genes upregulated in ESS", "a novel non-coding RNA (MALAT-1) to be expressed at significantly higher levels in stage-I and stage-II NSCLC primary tumours that subsequently metastasised", "quantitative RT-PCR verified overexpression in metastasizing samples. Several of the identified genes (eIF4A1, thymosin beta4 and a novel transcript named MALAT-1) were demonstrated to be significantly associated with metastasis in NSCLC patients ", "Σ RNA is a class of conserved large non-coding RNAs (murine Hepcarcin; human MALAT-1) up-regulated in carcinomas", "To date, most known NCTs studied have been relatively short, but several important regulatory NCTs, including XIST, MALAT-1, BC1 and BC200, are considerably larger in length", "These NCTs were among the most abundantly expressed transcripts detected", "The nuclear transcript MALAT-1 has been functionally associated with gene regulation and alternative splicing and its regulation has been shown to impact proliferation, apoptosis, migration and invasion" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/16441420", "http://www.ncbi.nlm.nih.gov/pubmed/23726266", "http://www.ncbi.nlm.nih.gov/pubmed/22722759", "http://www.ncbi.nlm.nih.gov/pubmed/15552795", "http://www.ncbi.nlm.nih.gov/pubmed/24163781", "http://www.ncbi.nlm.nih.gov/pubmed/18006640", "http://www.ncbi.nlm.nih.gov/pubmed/21266177", "http://www.ncbi.nlm.nih.gov/pubmed/23845456", "http://www.ncbi.nlm.nih.gov/pubmed/12970751", "http://www.ncbi.nlm.nih.gov/pubmed/16878148", "http://www.ncbi.nlm.nih.gov/pubmed/22858678", "http://www.ncbi.nlm.nih.gov/pubmed/23104528", "http://www.ncbi.nlm.nih.gov/pubmed/21678027", "http://www.ncbi.nlm.nih.gov/pubmed/22088988" ]

[]

[ "http://www.disease-ontology.org/api/metadata/DOID:162", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D062085", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D022661" ]

[ "Oxantel, a cholinergic anthelmintic and fumarate reductase inhibitor, significantly inhibited biofilm formation by P. gingivalis and disrupted established biofilms." ]

[ "Oxantel disrupts polymicrobial biofilm" ]

[ "Oxantel disrupts polymicrobial biofilm development of periodontal pathogens", "he anthelmintic drug oxantel has been shown to inhibit fumarate reductase (Frd) activity in some pathogenic bacteria and inhibit P. gingivalis homotypic biofilm formation.", "Oxantel, a cholinergic anthelmintic and fumarate reductase inhibitor, significantly inhibited biofilm formation by P. gingivalis and disrupted established biofilms at concentrations below its MIC against planktonic cells." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/20038616", "http://www.ncbi.nlm.nih.gov/pubmed/24165189" ]

[ { "p": "http://linkedlifedata.com/resource/pubmed/registryNumber", "s": "http://linkedlifedata.com/resource/pubmed/chemical/oxantel", "o": "36531-26-7" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://linkedlifedata.com/resource/pubmed/chemical/oxantel", "o": "oxantel" }, { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A0294401", "o": "MeSH" }, { "p": "http://linkedlifedata.com/resource/umls/prefMetaMap", "s": "http://linkedlifedata.com/resource/umls/id/C0163908", "o": "http://linkedlifedata.com/resource/umls/label/A0294401" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A0294401", "o": "oxantel pamoate" }, { "p": "http://www.w3.org/2008/05/skos-xl#prefLabel", "s": "http://linkedlifedata.com/resource/umls/id/C0163908", "o": "http://linkedlifedata.com/resource/umls/label/A0294401" } ]

[ "http://www.biosemantics.org/jochem#4251142", "http://www.disease-ontology.org/api/metadata/DOID:824", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D010518" ]

[ "Apelin, a small regulatory peptide, is the endogenous ligand for the apelin receptor (APJ) receptor." ]

[ "Apelin, a small regulatory peptide, is the endogenous ligand for the apelin receptor (APJ) receptor." ]

[ "Apelin, a small regulatory peptide, is the endogenous ligand for the apelin receptor (APJ) receptor.", "Apelin is an adipocyte-derived hormone that plays important roles in energy metabolism.", "Apelin, as the endogenous ligand of G protein-coupled receptor APJ, participates in a number of physiological and pathological processes. ", "Apelin is a novel bioactive peptide as the endogenous ligand for APJ.", "adipokine apelin ", "Apelin is the endogenous ligand of the APJ receptor, a member of the G protein-coupled receptor family.", "To date four adipokines (leptin, visfatin, apelin and ghrelin) have been investigated and all affect myometrial contractility, but some more potently than others.", "The adipocytokine apelin is a peptide, Apelin and its receptor are abundantly expressed in the nervous and cardiovascular systems.", "The aim of this study was to determine the levels of regulatory peptides apelin", "Apelin is a vaso-dilatory peptide that also has a modulatory role in pain processing. " ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/25668242", "http://www.ncbi.nlm.nih.gov/pubmed/25362565", "http://www.ncbi.nlm.nih.gov/pubmed/25486928", "http://www.ncbi.nlm.nih.gov/pubmed/25711427", "http://www.ncbi.nlm.nih.gov/pubmed/25931124", "http://www.ncbi.nlm.nih.gov/pubmed/25965959", "http://www.ncbi.nlm.nih.gov/pubmed/25380625", "http://www.ncbi.nlm.nih.gov/pubmed/26491547", "http://www.ncbi.nlm.nih.gov/pubmed/25491175", "http://www.ncbi.nlm.nih.gov/pubmed/26149233" ]

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[ "The main function of PABPC4 is in mRNA stability and translation initiation. PABPC4 may also play a role in chronic inflammation and in the pathogenesis of colorectal cancer." ]

[ "PABC4 is important for mRNA stability and translation initiation, in chronic inflammation and in the pathogenesis of colorectal cancer." ]

[ "In testis mRNA stability and translation initiation are extensively under the control of poly(A)-binding proteins (PABP).", "Taken together, our findings indicate that PABPC4 may play a role in the pathogenesis of colorectal cancer.", "Consistent with these biochemical activities, plus corresponding histological profiles, the identified RNA processing factors are predicted to collectively drive post-transcriptional expression of an alternative exome that fuels finishing steps of sperm maturation and fitness.", "This is the first evidence that PABPCs have a targeted role in hTERT regulation leading to a growth advantage in cells expressing HPV16 E6.", "to play a role in chronic inflammation (PPP1R3B, SALL1, PABPC4,", "and with the exception of PABP4, appear to be restricted in their expression to a small number of cell types. ", "PABPC4 (p(Het) = 0.034) for HDL-C. Our findings suggest that some of the previously identified variants associate differently with lipid traits in adolescents compared to adults, either because of developmental changes or because of greater interactions with environmental differences in adults.", "In addition, PABP4 was associated with the poly(A) tract of pre-mRNA" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/23938467", "http://www.ncbi.nlm.nih.gov/pubmed/22884093", "http://www.ncbi.nlm.nih.gov/pubmed/21300955", "http://www.ncbi.nlm.nih.gov/pubmed/23300856", "http://www.ncbi.nlm.nih.gov/pubmed/22530058", "http://www.ncbi.nlm.nih.gov/pubmed/21940797", "http://www.ncbi.nlm.nih.gov/pubmed/11328870", "http://www.ncbi.nlm.nih.gov/pubmed/20943973", "http://www.ncbi.nlm.nih.gov/pubmed/22896784", "http://www.ncbi.nlm.nih.gov/pubmed/23181716" ]

[ { "p": "http://purl.uniprot.org/core/reviewed", "s": "http://purl.uniprot.org/uniprot/P21187", "o": "true" }, { "p": "http://purl.uniprot.org/core/shortName", "s": "http://linkedlifedata.com/resource/#_5032313138370015", "o": "Poly(A)-binding protein" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://purl.uniprot.org/intact/EBI-103658", "o": "pAbp" }, { "p": "http://www.w3.org/2004/02/skos/core#exactMatch", "s": "http://purl.uniprot.org/intact/EBI-103658", "o": "http://purl.uniprot.org/uniprot/P21187" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_5032313138370015", "o": "Polyadenylate-binding protein" }, { "p": "http://purl.uniprot.org/core/recommendedName", "s": "http://purl.uniprot.org/uniprot/P21187", "o": "http://linkedlifedata.com/resource/#_5032313138370015" }, { "p": "http://purl.uniprot.org/core/shortName", "s": "http://linkedlifedata.com/resource/#_5032313138370015", "o": "PABP" } ]

[ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0006378", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D026723", "http://www.uniprot.org/uniprot/PABP_DROME", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D002352", "http://www.uniprot.org/uniprot/PABP4_HUMAN", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011485", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0043631", "http://www.biosemantics.org/jochem#4249823", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0005515", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0008143", "http://www.biosemantics.org/jochem#4002540" ]

[ "ABL-family proteins comprise one of the best conserved branches of the tyrosine kinases. Each ABL protein contains an SH3-SH2-TK (Src homology 3-Src homology 2-tyrosine kinase) domain cassette, which confers autoregulated kinase activity and is common among nonreceptor tyrosine kinases. This cassette is coupled to an actin-binding and -bundling domain, which makes ABL proteins capable of connecting phosphoregulation with actin-filament reorganization. Two vertebrate paralogs, ABL1 and ABL2, have evolved to perform specialized functions. ", "The Abelson (ABL) family of nonreceptor tyrosine kinases, ABL1 and ABL2, transduces diverse extracellular signals to protein networks that control proliferation, survival, migration and invasion. Constitutively activated mutants of the non-receptor tyrosine kinase (TK) ABL1 (Abelson murine leukemia viral (v-abl) homolog (1) protein) play a central role in the pathogenesis myeloproliferative disorders and in some cases of acute leukemia and lymphoma." ]

[ "Nonreceptor tyrosine kinase", "Protein-Tyrosine Kinase" ]

[ "The Abelson (ABL) family of nonreceptor tyrosine kinases, ABL1 and ABL2, transduces diverse extracellular signals to protein networks that control proliferation, survival, migration and invasion. ABL1 was first identified as an oncogene required for the development of leukaemias initiated by retroviruses or chromosome translocations. ", "Chromosomal rearrangements involving the ABL1 gene, leading to a BCR-ABL1 fusion gene, have been mainly associated with chronic myeloid leukemia and B-cell acute lymphoblastic leukemia (ALL). At present, six other genes have been shown to fuse to ABL1. The kinase domain of ABL1 is retained in all chimeric proteins that are also composed of the N-terminal part of the partner protein that often includes a coiled-coil or a helix-loop-helix domain. These latter domains allow oligomerization of the protein that is required for tyrosine kinase activation, cytoskeletal localization, and neoplastic transformation.", "ABL-family proteins comprise one of the best conserved branches of the tyrosine kinases. Each ABL protein contains an SH3-SH2-TK (Src homology 3-Src homology 2-tyrosine kinase) domain cassette, which confers autoregulated kinase activity and is common among nonreceptor tyrosine kinases. This cassette is coupled to an actin-binding and -bundling domain, which makes ABL proteins capable of connecting phosphoregulation with actin-filament reorganization. Two vertebrate paralogs, ABL1 and ABL2, have evolved to perform specialized functions. ", "Protein tyrosine kinases form a large family of signaling proteins implicated in both normal and malignant cell signaling. The aim of this study was to identify protein tyro-sine kinases that can transform hematopoietic cells to growth factor independent proliferation when constitutively activated by homodimerization. We used a modified retroviral insertion mutagenesis screen with a retroviral vector containing the homodimerization domain of ETV6 followed by an artificial splice donor site. Integration of this retroviral vector within a gene of the host genome would generate a fusion transcript containing the dimerization domain and part of the disrupted gene. Using this strategy with the IL3 dependent Ba/F3 cell line, we identified 8 different protein tyrosine kinases (Abl1, Fgfr1, Hck, Jak2, Lck, Mertk, Mst1r, Tnk1) that transformed the cells.", "Three families of tyrosine kinases have long been recognized to play critical roles in TCR-dependent signaling. They are the Src, zeta-associated protein of 70 kDa, and Tec families of kinases. More recently, the Abelson (Abl) tyrosine kinases have been shown to be activated by TCR engagement and to be required for maximal TCR signaling. Using T-cell conditional knockout mice deficient for Abl family kinases, Abl (Abl1) and Abl-related gene (Arg) (Abl2), it was recently shown that loss of Abl kinases results in defective T-cell development and a partial block in the transition to the CD4(+)CD8(+) stage. ", "ABL family tyrosine kinases are tightly regulated by autoinhibition and phosphorylation mechanisms. These kinases maintain an inactive conformation through intramolecular interactions involving SH3 and SH2 domains. RIN1, a downstream effector of RAS, binds to the ABL SH3 and SH2 domains and stimulates ABL tyrosine kinase activity.", "RIN1 binding to the ABL2 kinase resulted in a large decrease in Km and a small increase in Vmax toward an ABL consensus substrate peptide.", "RIN1 increased the kinase activity of both ABL1 and ABL2, and this occurred in the presence or absence of ABL regulatory domains outside the SH3-SH2-tyrosine kinase domain core.", "Constitutively activated mutants of the non-receptor tyrosine kinases (TK) ABL1 (Abelson murine leukemia viral (v-abl) homolog (1) protein) and JAK2 (JAnus Kinase 2 or Just Another Kinase 2) play a central role in the pathogenesis of clinically and morphologically distinct chronic myeloproliferative disorders but are also found in some cases of de novo acute leukemia and lymphoma.", "Abl1 (previously known as Abl) and the Abl1-related gene product Abl2 (previously known as Arg) define a family of tyrosine kinases that regulate actin structure and presynaptic axon guidance. Here we show that the Abl kinases are critical mediators of postsynaptic assembly downstream of agrin and MuSK. ", "The ABL1 proto-oncogene encodes a cytoplasmic and nuclear protein tyrosine kinase (c-Abl) that has been implicated in processes of cell differentiation, cell division, cell adhesion and stress response.", "Two essential proteins, Proto-oncogene tyrosine-protein kinase ABL1 (c-ABL) and Heat shock 70kDa protein 4 (Apg-2), were confirmed by Western blot and showed consistent changes with proteomic results.", "The ABL1 proto-oncogene encodes a cytoplasmic and nuclear protein tyrosine kinase (c-Abl) that has been implicated in processes of cell differentiation, cell division, cell adhesion and stress response" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/19794087", "http://www.ncbi.nlm.nih.gov/pubmed/20841568", "http://www.ncbi.nlm.nih.gov/pubmed/12796783", "http://www.ncbi.nlm.nih.gov/pubmed/19290927", "http://www.ncbi.nlm.nih.gov/pubmed/21435002", "http://www.ncbi.nlm.nih.gov/pubmed/23842646", "http://www.ncbi.nlm.nih.gov/pubmed/9500553", "http://www.ncbi.nlm.nih.gov/pubmed/18528425", "http://www.ncbi.nlm.nih.gov/pubmed/18796434", "http://www.ncbi.nlm.nih.gov/pubmed/24012954" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011519", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011518" ]

[ "The Romano Ward long QT syndrome (LQTS) has an autosomal dominant mode of inheritance." ]

[ "autosomal dominant" ]

[ "KCNQ1 is associated with two different entities of LQTS, the autosomal-dominant Romano-Ward syndrome (RWS), and the autosomal-recessive Jervell and Lange-Nielsen syndrome (JLNS) characterized by bilateral deafness in addition to cardiac arrhythmias.", "The Romano Ward long QT syndrome (LQTS) has an autosomal dominant mode of inheritance.", "The genetic forms of LQTS include Romano-Ward syndrome (RWS), which is characterized by isolated LQTS and an autosomal dominant pattern of inheritance, and syndromes with LQTS in association with other conditions.", "The Jervell and Lange-Nielsen syndrome (JLNS) is characterized by prolongation of the QT interval, deafness, and autosomal-recessive inheritance, and the Romano-Ward syndrome is characterized by a prolonged QT interval, autosomal-dominant inheritance, and no deafness. ", "Different mutations in KVLQT1 cause the dominant Romano-Ward (RW) syndrome and the recessive Jervell and Lange-Nielsen (JLN) syndrome, which, in addition to cardiac abnormalities, includes congenital deafness. ", "The Romano-Ward syndrome shows an autosomal dominant pattern of inheritance and normal hearing. ", "The Romano-Ward syndrome is of autosomal dominant inheritance, and the Jervell and Lange-Nielson syndrome, with associated deafness, of autosomal recessive inheritance. ", "Romano-Ward syndrome is a subtype of prolonged QT syndrome with autosomal dominant inheritance. ", "A family with the Romano-Ward syndrome is presented. This family showed typical features of this syndrome with QT prolongation, torsades de pointes ventricular tachycardia, sudden death and an autosomal dominant inheritance pattern. " ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/7994803", "http://www.ncbi.nlm.nih.gov/pubmed/10593671", "http://www.ncbi.nlm.nih.gov/pubmed/9272155", "http://www.ncbi.nlm.nih.gov/pubmed/8098062", "http://www.ncbi.nlm.nih.gov/pubmed/19862833", "http://www.ncbi.nlm.nih.gov/pubmed/15950200", "http://www.ncbi.nlm.nih.gov/pubmed/8223759", "http://www.ncbi.nlm.nih.gov/pubmed/2771275", "http://www.ncbi.nlm.nih.gov/pubmed/7695867", "http://www.ncbi.nlm.nih.gov/pubmed/10560244", "http://www.ncbi.nlm.nih.gov/pubmed/9302275", "http://www.ncbi.nlm.nih.gov/pubmed/8048706", "http://www.ncbi.nlm.nih.gov/pubmed/8180509" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D008133", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D029597", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D040582" ]

[ "H3K36m3 has been systematically associated to exon inclusion in almost all published studies. Other marks have been associated as well in specific studies to exon expression, but it can not be concluded that the effect of these marks in exon expression it is not a consequence of their effect in gene expression." ]

[]

[ "We found that several types of histone modifications including H3K36me3 were associated with the inclusion or exclusion of alternative exons. Furthermore, we observed that the levels of H3K36me3 and H3K79me1 in the cell lines were well correlated with the differences in alternative splicing patterns between the cell lines.", "Here we find that elevated levels of trimethylation of histone H3 on Lys9 (H3K9me3) are a characteristic of the alternative exons of several genes including CD44.", "he first report shows that a physiological stimulus such as neuron depolarization promotes intragenic histone acetylation (H3K9ac) and chromatin relaxation, causing the skipping of exon 18 of the neural cell adhesion molecule gene.", "Using small interfering RNAs (siRNAs), we increased the levels of H3K9me2 and H3K27me3 in the proximity of alternative exon 33 of the human fibronectin gene, favoring its inclusion into mature messenger RNA (mRNA) through a mechanism that recalls RNA-mediated transcriptional gene silencing.", "Among the 38 histone modifications analyzed in man, H3K36me3, H3K79me1, H2BK5me1, H3K27me1, H3K27me2, and H3K27me3 had evidently higher signals in internal exons than in the following introns and were clearly related to exon expression" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/21289049", "http://www.ncbi.nlm.nih.gov/pubmed/20407423", "http://www.ncbi.nlm.nih.gov/pubmed/19687145", "http://www.ncbi.nlm.nih.gov/pubmed/19182803", "http://www.ncbi.nlm.nih.gov/pubmed/20133523", "http://www.ncbi.nlm.nih.gov/pubmed/22242188", "http://www.ncbi.nlm.nih.gov/pubmed/21358630", "http://www.ncbi.nlm.nih.gov/pubmed/22455468", "http://www.ncbi.nlm.nih.gov/pubmed/21057525", "http://www.ncbi.nlm.nih.gov/pubmed/21173847", "http://www.ncbi.nlm.nih.gov/pubmed/22345622", "http://www.ncbi.nlm.nih.gov/pubmed/23353998" ]

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[ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D042421", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D017398" ]

[ "Phospholamban (PLB) is a sarcoplasmic reticulum (SR) protein that is phosphorylated at Ser16 by PKA. Phosphorylation of PLB by PKA reverses the inhibitory action of PLB." ]

[ "yes" ]

[ "cAMP-dependent protein kinase (PKA) phosphorylation of PLB", "phosphorylation of PLN, at either Ser(16) by PKA ", "Activation of cardiac muscle sarcoplasmic reticulum Ca2+-ATPase (SERCA2a) by beta1-agonists involves cAMP- and PKA-dependent phosphorylation of phospholamban (PLB), which relieves the inhibitory effects of PLB on SERCA2a. ", "Phospholamban (PLB) is a sarcoplasmic reticulum (SR) protein that when phosphorylated at Ser16 by PKA", "phosphorylation of PLB by the Ca2+-calmodulin-dependent protein kinase (CaMK) and cAMP-dependent protein kinase (PKA). ", "cAMP-dependent protein kinase (PKA)-mediated phospholamban (PLB) phosphorylation at serine-16", "Phospholamban (PLB) is a major target of the beta-adrenergic cascade in the heart, functioning to modulate contractile force by altering the rate of calcium re-sequestration by the Ca-ATPase. Functionally, inhibition by PLB binding is manifested by shifts in the calcium dependence of Ca-ATPase activation toward higher calcium levels; phosphorylation of PLB by PKA reverses the inhibitory action of PLB.", "phosphorylation of both PLB residues (Ser16, PKA site, and Thr17, CaMKII site) ", "Phosphorylation of Ser(16) by PKA", "stabilization of the structure of PLB following phosphorylation of Ser(16)", "Phospholamban (PLB) inhibits the sarcoplasmic reticulum (SR) Ca(2+)-ATPase, and this inhibition is relieved by cAMP-dependent protein kinase (PKA)-mediated phosphorylation. ", "Two-dimensional tryptic peptide maps of phosphorylated phospholamban indicated that cAMP-dependent protein kinase phosphorylates at a single site, A, and Ca2+-calmodulin-dependent protein kinase phosphorylates at sites C1 and C2 in the low molecular weight form, where A is different from C1 but may be the same as C2.", "Because SR function is regulated by phosphorylation of phospholamban (PLB), a SR protein phosphorylated by cAMP-dependent protein kinase (PKA) at Ser(16)and Ca(2+)-calmodulin-dependent protein kinase (CaMKII) at Thr(17), the phosphorylation of these residues during ischemia and reperfusion was examined in Langendorff-perfused rat hearts", "These changes were associated with reduced protein expression of sarcoplasmic reticulum Ca(2+)-ATPase (SERCA2a) and protein kinase A phosphorylated phospholamban (PLB), which was reduced in HF, but essentially abolished in VD-HF", "The data indicate that 1) phosphorylation of phospholamban at Ser16 by cAMP-dependent protein kinase is the main regulator of beta-adrenergic-induced cardiac relaxation definitely preceding Thr17 phosphorylation and 2) the beta-adrenergic-mediated phosphorylation of Thr17 by Ca2+-calmodulin-dependent protein kinase required influx of Ca2+ through the L-type Ca2+ channel", "Here we extend this model to explain the reversal of SERCA2a inhibition that occurs after phosphorylation of PLB at Ser(16) by protein kinase A (PKA) and after binding of the anti-PLB monoclonal antibody 2D12, which recognizes residues 7-13 of PLB", "Phospholamban is phosphorylated in heart by cAMP-dependent protein kinase, cGMP-dependent protein kinase and calcium/calmodulin-dependent protein kinase II (CM-kinase-II) and in smooth muscle cells by cGMP-dependent protein kinase", "Phospholamban, the cardiac sarcoplasmic reticulum proteolipid, is phosphorylated by cAMP-dependent protein kinase, by Ca2+/phospholipid-dependent protein kinase, and by an endogenous Ca2+/calmodulin-dependent protein kinase, the identity of which remains to be defined" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/14577598", "http://www.ncbi.nlm.nih.gov/pubmed/12962492", "http://www.ncbi.nlm.nih.gov/pubmed/15909986", "http://www.ncbi.nlm.nih.gov/pubmed/11502581", "http://www.ncbi.nlm.nih.gov/pubmed/7857766", "http://www.ncbi.nlm.nih.gov/pubmed/19191503", "http://www.ncbi.nlm.nih.gov/pubmed/17548345", "http://www.ncbi.nlm.nih.gov/pubmed/15524173", "http://www.ncbi.nlm.nih.gov/pubmed/10330247", "http://www.ncbi.nlm.nih.gov/pubmed/15049694", "http://www.ncbi.nlm.nih.gov/pubmed/11812163", "http://www.ncbi.nlm.nih.gov/pubmed/3730367", "http://www.ncbi.nlm.nih.gov/pubmed/15362510", "http://www.ncbi.nlm.nih.gov/pubmed/15229104", "http://www.ncbi.nlm.nih.gov/pubmed/16600289", "http://www.ncbi.nlm.nih.gov/pubmed/16226237" ]

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[]

[ "Yes, telemedicine is feasible and cost-effective for education and therapy of patients with chronic pain.", "Yes, there are." ]

[ "yes" ]

[ "An integrated cognitive-behavioral and physical therapy group protocol has been developed and then implemented at remote sites using videoconferencing technology to provide pain management for veterans. ", "Tele-pain management: use of videoconferencing technology in the delivery of an integrated cognitive-behavioral and physical therapy group intervention.", "It is feasible to provide treatment to women veterans living in rural areas by utilizing video-teleconferencing technology between larger VA medical centers and facilities at CBOCs in more rural settings", "The results suggest that a smartphone-delivered intervention with diaries and personalized feedback can reduce catastrophizing and prevent increases in functional impairment and symptom levels in women with chronic widespread pain following inpatient rehabilitation.", " Of the studies available, there are very few randomized trials of telehealth pain care and only one general overview of e-health and chronic pain, which dedicates just a few paragraphs to telehealth.", "therapy adaptation and the resultant specification for the SMART2 project-a technology-based self-management system for assisting long-term health conditions, including chronic pain", "Results showed the use of videoconferencing for this group of patients is useable and satisfactory for both patients and staff, that the patients save time and money, and that for a system where videoconferencing equipment is already in use, it is also cost effective. Staff were able to identify new patient problems. ", "This pilot study indicates that telemedicine follow-up consultations for chronic pain patients are feasible and cost-saving. Patients and anesthesiologists were highly satisfied with telemedicine consultation." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/23659470", "http://www.ncbi.nlm.nih.gov/pubmed/21375412", "http://www.ncbi.nlm.nih.gov/pubmed/23291270", "http://www.ncbi.nlm.nih.gov/pubmed/22662734", "http://www.ncbi.nlm.nih.gov/pubmed/16691087", "http://www.ncbi.nlm.nih.gov/pubmed/22303839", "http://www.ncbi.nlm.nih.gov/pubmed/17336868" ]

[]

[]

[ "Processing bodies (P bodies, PB) are cytoplasmic protein complexes involved in degradation and translational arrest of mRNA." ]

[]

[ " processing (P) bodies, a site for mRNA degradation.", "processing bodies are RNA-containing granules that contribute to this process by modulating cellular signaling pathways, metabolic machinery, and stress response programs. ", "translationally repressed mRNAs localize to P-bodies and stress granules where their decay and storage, respectively, are directed. ", "stress-dependent formation of P-bodies.", " P-bodies involved in RNA metabolism", "cytoplasmic RNA granules called processing bodies (P-bodies)", "The 5'-to-3' mRNA degradation machinery localizes to cytoplasmic processing bodies (P-bodies), which are non-membranous structures found in all eukaryotes. ", "This analysis demonstrates the dual role of P-bodies as decay sites and storage areas under regular and stress conditions.", " mRNA P-bodies (processing bodies) harbour much of the mRNA decay machinery", "P-bodies contain the mRNA decay and translational repression machineries ", "P-bodies belong to a large family of RNA granules that are associated with post-transcriptional gene regulation, conserved from yeast to mammals, and influence biological processes ranging from germ cell development to neuronal plasticity.", "In eukaryotic cells, components of the 5' to 3' mRNA degradation machinery can undergo a rapid phase transition. The resulting cytoplasmic foci are referred to as processing bodies (P-bodies). ", "Processing bodies (P bodies, PB) are cytoplasmic protein complexes involved in degradation and translational arrest of mRNA.", "The mRNA processing body (P-body) is a cellular structure that regulates the stability of cytoplasmic mRNA.", "while most other messenger RNAs (mRNAs) are stored away in stress granules or degraded in processing bodies (P-bodies).", "Numerous mRNAs are degraded in processing bodies (P bodies) in Saccharomyces cerevisiae.", "Processing (P)-bodies are cytoplasmic RNA protein aggregates responsible for the storage, degradation, and quality control of translationally repressed messenger RNAs in eukaryotic cells.", "in P-bodies (PBs), where translationally silenced mRNAs are deposited, ", "Processing bodies (P-bodies) are cytoplasmatic mRNP granules containing non-translating mRNAs and proteins from the mRNA decay and silencing machineries. ", "The control of mRNA translation and degradation is mediated in part by a set of proteins that can inhibit translation and promote decapping, as well as function in the assembly of cytoplasmic mRNP granules referred to as processing bodies (P-bodies). " ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/25529221", "http://www.ncbi.nlm.nih.gov/pubmed/24918601", "http://www.ncbi.nlm.nih.gov/pubmed/25437551", "http://www.ncbi.nlm.nih.gov/pubmed/24862735", "http://www.ncbi.nlm.nih.gov/pubmed/25514416", "http://www.ncbi.nlm.nih.gov/pubmed/25128566", "http://www.ncbi.nlm.nih.gov/pubmed/25416063", "http://www.ncbi.nlm.nih.gov/pubmed/25339350", "http://www.ncbi.nlm.nih.gov/pubmed/25110026", "http://www.ncbi.nlm.nih.gov/pubmed/24659297", "http://www.ncbi.nlm.nih.gov/pubmed/25110034", "http://www.ncbi.nlm.nih.gov/pubmed/24860588", "http://www.ncbi.nlm.nih.gov/pubmed/24418890", "http://www.ncbi.nlm.nih.gov/pubmed/24292556", "http://www.ncbi.nlm.nih.gov/pubmed/25482014", "http://www.ncbi.nlm.nih.gov/pubmed/24755989", "http://www.ncbi.nlm.nih.gov/pubmed/24569876", "http://www.ncbi.nlm.nih.gov/pubmed/24525673", "http://www.ncbi.nlm.nih.gov/pubmed/24504254" ]

[]

[ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0043186", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0000932", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0033962", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0010494" ]

[ "Decitabine reactivates unmethylated p21WAF1 in some AML cell lines but the possible occurrence of p21WAF1 methylation in AML in vivo has not been studied in detail and decitabine effects on p21WAF1 chromatin remodeling have not been reported. We also discuss the following questions: What is the best administration schedule of decitabine in solid tumors? Is there tumor type specificity for decitabine-based epigenetic therapy? We found that p21WAF1 mRNA was undetectable in 6 of 24 AML patient samples and 4 of 5 AML cell lines but there was no evidence of p21WAF1 promoter methylation.", "The use of the DNA methylation inhibitor decitabine (Dacogen®) has been approved in the treatment of hematological malignancies, and its clinical effects on solid tumors have gained attention.", "Decitabine is a potent demethylating agent that exhibits clinical activity against myeloid malignancies. Numerous genes silenced by hypermethylation are reactivated by decitabine through a mechanism involving promoter demethylation with subsequent release of histone deacetylases (HDACs) and accumulation of acetylated histones. Recent studies indicating that decitabine also induces regional chromatin remodeling of some unmethylated genes suggest additional mechanisms of action." ]

[]

[ "The use of the DNA methylation inhibitor decitabine (Dacogen®) has been approved in the treatment of hematological malignancies, and its clinical effects on solid tumors have gained attention.", "low-dose decitabine and combined therapy show significant improvement in solid tumor treatment.", "Here, we demonstrate dose-dependent degradation of Dnmt1 in mouse embryonic stem (ES) cells expressing catalytic site mutant (cys-ser), confirming that the covalent bond formation between Dnmt1 and decitabine-incorporated DNA is not essential for this process.", "NMT1o, the oocyte-specific isoform that lacks the N-terminal 118-amino acid domain, did not undergo decitabine-mediated degradation, which further proves the requirement of multiple domains including nuclear localization signa", "Analysis of glycerol density gradient fractions of micrococcal nuclease-digested nuclei showed that both nucleosomal and nucleoplasmic DNMT1 are degraded upon decitabine treatment.", "The maximal effect caused by inhibiting protein kinase C (PKC) persuaded us to investigate further its role in decitabine-mediated DNMT1 degradation. ", "These studies provide substantial evidence that decitabine-induced degradation of the maintenance methyltransferase DNMT1 does not require covalent bond formation with the substrate and also elucidate its underlying molecular mechanism.", "Decitabine is a potent demethylating agent that exhibits clinical activity against myeloid malignancies. Numerous genes silenced by hypermethylation are reactivated by decitabine through a mechanism involving promoter demethylation with subsequent release of histone deacetylases (HDACs) and accumulation of acetylated histones. Recent studies indicating that decitabine also induces regional chromatin remodeling of some unmethylated genes suggest additional mechanisms of action.", "Our findings indicate that decitabine can relieve p21WAF1 repression in AML by a mechanism that involves release of HDAC1 without requiring promoter demethylation.", "Numerous genes silenced by hypermethylation are reactivated by decitabine through a mechanism involving promoter demethylation with subsequent release of histone deacetylases (HDACs) and accumulation of acetylated histones.", "5-Aza-2'-deoxycytidine (decitabine) can relieve p21WAF1 repression in human acute myeloid leukemia by a mechanism involving release of histone deacetylase 1 (HDAC1) without requiring p21WAF1 promoter demethylation.", "Decitabine, a demethylating drug, is the first-line treatment for myelodysplastic syndromes and gains better overall survival, which is based on epigenetic mechanism", "Demethylating agent decitabine was reported to be able to up-regulate CTAs through its hypomethylation mechanism, thus enhance the immunogenicity of leukemia cells", "However, further elucidation of its mechanism of action is required, as clinical response to decitabine does not correlate with demethylation of the p15 gene promoter or the repetitive DNA element LINE. ", "In the area of epigenetic therapy, the demethylating drug decitabine (5-aza-2'-deoxycytidine) is increasingly used to treat acute myelogenous leukemia and myelodysplastic syndrome, but the mechanisms of its anticancer activity have remained unclear. ", "An epigenetic approach to the treatment of advanced MDS; the experience with the DNA demethylating agent 5-aza-2'-deoxycytidine (decitabine) in 177 patients.", "Numerous genes silenced by hypermethylation are reactivated by decitabine through a mechanism involving promoter demethylation with subsequent release of histone deacetylases (HDACs) and accumulation of acetylated histones. Recent studies indicating that decitabine also induces regional chromatin remodeling of some unmethylated genes suggest additional mechanisms of action.", "However, further elucidation of its mechanism of action is required, as clinical response to decitabine does not correlate with demethylation of the p15 gene promoter or the repetitive DNA element LINE." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/25130173", "http://www.ncbi.nlm.nih.gov/pubmed/25123082", "http://www.ncbi.nlm.nih.gov/pubmed/16043219", "http://www.ncbi.nlm.nih.gov/pubmed/24286424", "http://www.ncbi.nlm.nih.gov/pubmed/16273408", "http://www.ncbi.nlm.nih.gov/pubmed/16585166", "http://www.ncbi.nlm.nih.gov/pubmed/22893792", "http://www.ncbi.nlm.nih.gov/pubmed/16211386" ]

[]

[ "http://www.biosemantics.org/jochem#4269908", "http://www.biosemantics.org/jochem#http://www.biosemantics.org/jochem#:4269908" ]

[ "Mutations in the gene coding for the transcription factor RFX6 (regulatory factor X,6) have been described as the cause of the Mitchell-Riley syndrome." ]

[ "RFX6" ]

[ "Mutations in rfx6 were recently associated with Mitchell-Riley syndrome, which involves neonatal diabetes, and other digestive system defects. ", "bi-allelic mutations in the transcription factor RFX6 were described as the cause of a rare condition characterized by neonatal diabetes with pancreatic and biliary hypoplasia and duodenal/jejunal atresia." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/21215266", "http://www.ncbi.nlm.nih.gov/pubmed/23914949" ]

[ { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A17467973", "o": "OMIM" }, { "p": "http://www.w3.org/2008/05/skos-xl#prefLabel", "s": "http://linkedlifedata.com/resource/umls/id/C2748662", "o": "http://linkedlifedata.com/resource/umls/label/A17467973" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A17467973", "o": "MITCHELL-RILEY SYNDROME" } ]

[ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004402", "http://www.disease-ontology.org/api/metadata/DOID:0050657", "http://www.disease-ontology.org/api/metadata/DOID:11589", "http://www.disease-ontology.org/api/metadata/DOID:225", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013577" ]

[ "There is no evidence that paramyxovirus are involved in etiology of subacute thyroiditis." ]

[ "no" ]

[ "Most cases of subacute thyroiditis are caused by a variety of viruses, for example, Coxsackie, cytomegalovirus, Epstein-Barr virus, and adenovirus. Influenza immunization or infection may cause subacute thyroiditis.", "Coxsackie virus has been reported to be one of the viruses associated with the disease.", "The etiology of subacute granulomatous thyroiditis (SAT) is obscure, although it is postulated to be associated with viral infections and genetic factors.", "The results suggest that SAT is not usually associated with acute infections", "No evidence was obtained to support the proposed role of enteroviruses as an important etiologic agent of SAT.", "The viral antibodies evaluated were those of Influenza A and B, Coxsackie A9, B1, B2, B3, B4, B5 and B6, Echo 3, 7, 11 and 12, Parainfluenza 1, 2, 3 and 4, and Adeno 8 virus. The following results were obtained: In class I HLA typing, the frequency of HLA-Bw35 in SAT was 67.4%, which was significantly (p less than 0.0001) higher than that in the control (14.1%). On the other hand, the frequency of Cw1 in SAT (14.6%) was significantly (p less than 0.01) lower than that of the control (32.1%), and that of Cw3 (65.2%) was significantly (p less than 0.01) higher than that of the control (46.5%)." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/22819125", "http://www.ncbi.nlm.nih.gov/pubmed/1691523", "http://www.ncbi.nlm.nih.gov/pubmed/20960165", "http://www.ncbi.nlm.nih.gov/pubmed/806773", "http://www.ncbi.nlm.nih.gov/pubmed/16279854", "http://www.ncbi.nlm.nih.gov/pubmed/22459018", "http://www.ncbi.nlm.nih.gov/pubmed/2998895", "http://www.ncbi.nlm.nih.gov/pubmed/20886354", "http://www.ncbi.nlm.nih.gov/pubmed/1180050", "http://www.ncbi.nlm.nih.gov/pubmed/9637274", "http://www.ncbi.nlm.nih.gov/pubmed/9797" ]

[ { "p": "http://www.w3.org/2004/02/skos/core#altLabel", "s": "http://linkedlifedata.com/resource/diseaseontology/id/DOID:7165", "o": "Granulomatous thyroiditis" } ]

[ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013968", "http://www.disease-ontology.org/api/metadata/DOID:7165", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D018109", "http://www.disease-ontology.org/api/metadata/DOID:7187", "http://www.disease-ontology.org/api/metadata/DOID:7166" ]

[ "Weight-loss mobile applications\npediatric obesity prevention and treatment, healthy eating, and physical activity promotion\nA total of 229 dermatology-related apps were identified in the following categories: general dermatology reference (61 [26.6%]), self-surveillance/diagnosis (41 [17.9%]), disease guide (39 [17.0%]), educational aid (20 [8.7%]), sunscreen/UV recommendation (19 [8.3%]), calculator (12 [5.2%]), teledermatology (8 [3.5%]), conference (6 [2.6%]), journal (6 [2.6%]), photograph storage/sharing (5 [2.2%]), dermoscopy (2 [0.9%]), pathology (2 [0.9%]), and other (8 [3.5%]). The most reviewed apps included Ultraviolet ~ UV Index (355 reviews), VisualDx (306), SPF (128), iSore (61), and SpotMole (50)\nmobile health and fitness app\nalcohol-use behavior change or recovery\nMore than 17,000 mHealth apps now are available for smart phones and other devices, and they do everything from monitoring urine flow for patients with enlarged prostates to reminding people prone to kidney stones to drink more water." ]

[ "weight loss", "exercise", "physical activity", "fitness", "dermatology", "alcohol-use behavior change", "urine flow", "fluid intake" ]

[ "Evidence-based strategies in weight-loss mobile apps", "Weight-loss mobile applications (apps) have the potential to be a helpful tool", "Mobile apps for pediatric obesity prevention and treatment, healthy eating, and physical activity promotion", "Mobile applications (apps) offer a novel way to engage children in behavior change,", "Mobile applications in dermatology", "A total of 229 dermatology-related apps were identified in the following categories: general dermatology reference (61 [26.6%]), self-surveillance/diagnosis (41 [17.9%]), disease guide (39 [17.0%]), educational aid (20 [8.7%]), sunscreen/UV recommendation (19 [8.3%]), calculator (12 [5.2%]), teledermatology (8 [3.5%]), conference (6 [2.6%]), journal (6 [2.6%]), photograph storage/sharing (5 [2.2%]), dermoscopy (2 [0.9%]), pathology (2 [0.9%]), and other (8 [3.5%]). The most reviewed apps included Ultraviolet ~ UV Index (355 reviews), VisualDx (306), SPF (128), iSore (61), and SpotMole (50).", " Twenty-seven mobile apps were identified and reviewed that involved general pharmacy practice, including apps that involved drug references, clinical references, medical calculators, laboratory references, news and continuing medical education, and productivity.", "Today, many high quality mobile apps are available for users and health professionals and cover the whole health care chain, i.e. information collection, prevention, diagnosis, treatment and monitoring", "Our team has developed a mobile health and fitness app called myFitnessCompanion® ", "to examine the current available mobile smartphone applications (e.g., apps) that utilize principles of ecological momentary assessment (EMA)-daily self-monitoring or near real-time self-assessment of alcohol-use behavior-to promote positive behavior change, alcohol harm reduction, psycho-education about alcohol use, or abstinence from alcohol.", "few apps addressed alcohol-use behavior change or recovery. Aside from tracking drinking consumption, a minority utilized empirically based components of alcohol treatment.", "More than 17,000 mHealth apps now are available for smart phones and other devices, and they do everything from monitoring urine flow for patients with enlarged prostates to reminding people prone to kidney stones to drink more water." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/22942063", "http://www.ncbi.nlm.nih.gov/pubmed/24073184", "http://www.ncbi.nlm.nih.gov/pubmed/24067948", "http://www.ncbi.nlm.nih.gov/pubmed/24139770", "http://www.ncbi.nlm.nih.gov/pubmed/21689119", "http://www.ncbi.nlm.nih.gov/pubmed/23821609", "http://www.ncbi.nlm.nih.gov/pubmed/21591562" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D063731", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D017216" ]

[ "Yes. The aurora B kinase and the polycomb protein ring1B combine to regulate active promoters in quiescent lymphocytes." ]

[ "yes" ]

[ "The aurora B kinase and the polycomb protein ring1B combine to regulate active promoters in quiescent lymphocytes.", "We show that the Aurora B kinase and the polycomb protein Ring1B have essential roles in regulating transcriptionally active genes in quiescent lymphocytes. Ring1B and Aurora B bind to a wide range of active promoters in resting B and T cells. Conditional knockout of either protein results in reduced transcription and binding of RNA Pol II to promoter regions and decreased cell viability. Aurora B phosphorylates histone H3S28 at active promoters in resting B cells as well as inhibiting Ring1B-mediated ubiquitination of histone H2A and enhancing binding and activity of the USP16 deubiquitinase at transcribed genes. Our results identify a mechanism for regulating transcription in quiescent cells that has implications for epigenetic regulation of the choice between proliferation and quiescence.", "We show that the Aurora B kinase and the polycomb protein Ring1B have essential roles in regulating transcriptionally active genes in quiescent lymphocytes.", "We show that the Aurora B kinase and the polycomb protein Ring1B have essential roles in regulating transcriptionally active genes in quiescent lymphocytes. Ring1B and Aurora B bind to a wide range of active promoters in resting B and T cells. Conditional knockout of either protein results in reduced transcription and binding of RNA Pol II to promoter regions and decreased cell viability. ", "We show that the Aurora B kinase and the polycomb protein Ring1B have essential roles in regulating transcriptionally active genes in quiescent lymphocytes. Ring1B and Aurora B bind to a wide range of active promoters in resting B and T cells." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/24034696" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D064127", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D064107", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D063146", "http://www.biosemantics.org/jochem#4262561" ]

[ "To date, 8 genes have been associated with Dyskeratosis Congenita development. These are DKC1, TERC, TERT, NOP10, NHP2, TIN2, C16orf57, and TCAB1. Seven of these are important in telomere maintenance, because either they encode components of the telomerase enzyme complex (DKC1, TERC, TERT, NOP10, NHP2, and TCAB1) or the shelterin complex (TINF2).", "To date, CTC1, DKC1, TERC, TERT, TINF2, NHP2, NOP10, and WRAP53 are the genes in which mutations are known to cause DC and result in very short telomeres Seven of these are important in telomere maintenance either because they encode components of the telomerase enzyme complex (DKC1, TERC, TERT, NOP10, NHP2, and TCAB1) or the shelterin complex (TINF2) " ]

[ "DKC1", "TERC", "TERT", "NOP10", "NHP2", "TIN2", "C16orf57", "TCAB1" ]

[ "Studies over the last 15 years have led to significant advances, with 8 DC genes (DKC1, TERC, TERT, NOP10, NHP2, TIN2, C16orf57, and TCAB1) having been characterized", "Seven of these are important in telomere maintenance either because they encode components of the telomerase enzyme complex (DKC1, TERC, TERT, NOP10, NHP2, and TCAB1) or the shelterin complex (TINF2)", "Dyskeratosis congenita (DC) is a heterogeneous bone marrow failure syndrome with seven disease-causing genes identified to date, six of which are linked to telomere maintenance. Mutations in one of these genes (TINF2), which encodes a component of the shelterin complex, are associated with particularly short telomeres", "Dyskeratosis congenita (DC) is an inheritable bone marrow failure syndrome characterized by reticulated hyperpigmentation, dystrophic nails and oral leukoplakia", "Four genes, namely DKC1 (codes for dyskerin), TERC and TERT (code for telomerase) and NOP10, have been implicated in the pathogenesis", "To date, CTC1, DKC1, TERC, TERT, TINF2, NHP2, NOP10, and WRAP53 are the genes in which mutations are known to cause DC and result in very short telomeres", "The mode of inheritance of DC varies by gene: DKC1 (X-linked), TERC and TINF2 (autosomal dominant), TERT (autosomal dominant or autosomal recessive), CTC1, WRAP53, NHP2, and NOP10 (autosomal recessive)", "Six genes have been identified, defects in which cause different genetic subtypes (X-linked recessive, autosomal dominant, autosomal recessive) of DC. The products of these genes encode components that are critical for telomere maintenance; either because they are core constituents of telomerase (dyskerin, TERC, TERT, NOP10 and NHP2) or are part of the shelterin complex that protects the telomeric end (TIN2)", "BACKGROUND: Telomerase complex genes mutations (DKC1, TERC, TERT, and NOP10) lead to premature telomere shortening and are responsible for different forms of dyskeratosis congenita.", "Mutations in DKC1 gene encoding dyskerin are responsible for the X-linked dyskeratosis congenita.", "The DC1 gene responsible for the X linked form (MIM 305000) of dyskeratosis congenita has been mapped to Xq28.", "The DC1 gene responsible for the X linked form (MIM 305000) of dyskeratosis congenita has been mapped to Xq28", "Mutations in DKC1 gene encoding dyskerin are responsible for the X-linked dyskeratosis congenita", "Mutations in the DKC1 gene are responsible for causing X-linked recessive dyskeratosis congenita (DKC) and a more severe allelic variant of the disease, Hoyeraal-Hreidarsson syndrome", "Telomerase complex genes mutations (DKC1, TERC, TERT, and NOP10) lead to premature telomere shortening and are responsible for different forms of dyskeratosis congenita", "Linkage analysis in multiplex families confirmed that the DKC1 gene, responsible for the X-linked form of DC, is located within Xq28 and facilitated its positional cloning", "DKC1 has been identified as the gene responsible for X-linked DC, and genetic analyses have been performed in a worldwide study" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/10903840", "http://www.ncbi.nlm.nih.gov/pubmed/22160078", "http://www.ncbi.nlm.nih.gov/pubmed/21199492", "http://www.ncbi.nlm.nih.gov/pubmed/20301779", "http://www.ncbi.nlm.nih.gov/pubmed/18989882", "http://www.ncbi.nlm.nih.gov/pubmed/15842668", "http://www.ncbi.nlm.nih.gov/pubmed/20687509", "http://www.ncbi.nlm.nih.gov/pubmed/19419704", "http://www.ncbi.nlm.nih.gov/pubmed/15304085", "http://www.ncbi.nlm.nih.gov/pubmed/9863595", "http://www.ncbi.nlm.nih.gov/pubmed/9886310" ]

[]

[ "http://www.disease-ontology.org/api/metadata/DOID:2729" ]

[ "CD99 is a 32-kDa transmembrane glycoprotein that is encoded by the MIC2 gene ", "CD99 is a transmembrane protein encoded by MIC2 gene. It is involved in multiple cellular functions, including cell adhesion and migration, apoptosis, cell differentiation, and regulation of protein trafficking, in either physiological or pathological conditions." ]

[ "yes" ]

[ "We report 2 unusual cytogenetic findings in a pediatric Ewing sarcoma, an insertion of the MIC2 gene encoding CD99 from Xp to 10p and a submicroscopic deletion of the well-known tumor supressor gene KLF6", "We obtained the final diagnosis of ES/PNET by immunohistochemical molecular study with positive staining for the MIC2 gene product (CD99) and a Ewing sarcoma breakpoint region 1 (EWSR1) gene rearrangement", "CD99, a transmembrane protein encoded by MIC2 gene is involved in multiple cellular events including cell adhesion and migration, apoptosis, cell differentiation and regulation of protein trafficking either in physiological or pathological conditions", "CD99 is a 32-kDa transmembrane glycoprotein that is encoded by the MIC2 gene", "The surgical specimens showed small round cell tumor with positive staining for MIC2 gene product (CD99)", "CD99 is a 32-kDa transmembrane glycoprotein that is encoded by the MIC2 gene.", "The leukocyte surface molecule CD99 is an integral membrane glycoprotein encoded by the E2/MIC2 gene.", "Human CD99, which is encoded by the mic2 gene, is a ubiquitous 32 kDa transmembrane protein.", "Human CD99 is a 32-kDa cell surface protein that is encoded by the MIC2 gene localized to the PAR1.", "The tumors displayed intense immunoreactivity in a membranous pattern for CD99, the cell surface glycoprotein encoded by the MIC2 gene.", "CD99, a transmembrane protein encoded by MIC2 gene is involved in multiple cellular events including cell adhesion and migration, apoptosis, cell differentiation and regulation of protein trafficking either in physiological or pathological conditions.", "CD99, the product of the MIC2 gene, exhibits an erythroid-specific quantitative polymorphism coregulated with the polymorphism of the XG blood group gene.", "CD99, the product of the MIC2 gene, exhibits an erythroid-specific quantitative polymorphism co-regulated with the Xga blood group polymorphism.", "Homology searches resulted in finding homologous sequences (totally about 40% homology) in the human MIC2 gene product (CD99; 32-kDa) of T lymphocytes.", "Although considered a specific marker for Ewing's sarcoma/peripheral neuroectodermal tumour, the MIC2 gene product (CD99) has been immunolocalised in a variety of human tumours.", "MIC2, the gene encoding the CD99 antigen, is found in the pseudoautosomal region of both the X and Y chromosomes.", "Human CD99 is a 32-kDa cell surface protein that is encoded by the MIC2 gene localized to the PAR1.", "The tumors displayed intense immunoreactivity in a membranous pattern for CD99, the cell surface glycoprotein encoded by the MIC2 gene.", "CD99 (MIC2) regulates the LFA-1/ICAM-1-mediated adhesion of lymphocytes, and its gene encodes both positive and negative regulators of cellular adhesion.", "Relation of neurological marker expression and EWS gene fusion types in MIC2/CD99-positive tumors of the Ewing family.", "The Ewing family of tumors (EFT) is characterized by high MIC2/CD99 expression and specific EWS/ETS gene rearrangements, resulting in different chimeric transcripts.", "The tumors displayed intense immunoreactivity in a membranous pattern for CD99, the cell surface glycoprotein encoded by the MIC2 gene.", "Monoclonal antibody (MAb) HBA71, which was raised against Ewing's sarcoma cells, recognizes a cell-surface glycoprotein, p30/32MIC2, that is encoded by the MIC2 gene in the pseudoautosomal region of human chromosomes X and Y.", "Monoclonal antibodies (mAbs) directed against E2, a 32-kDa transmembrane protein encoded by the MIC2 gene located in the pseudoautosomal region, induce a transbilayer movement of phosphatidylserine and, to a lesser extent, phosphatidylethanolamine in human thymocytes and a Jurkat T lymphocytes.", "Homology searches resulted in finding homologous sequences (totally about 40% homology) in the human MIC2 gene product (CD99; 32-kDa) of T lymphocytes.", "CD99 is a 32-kDa transmembrane glycoprotein that is encoded by the MIC2 gene", "CD99, a transmembrane protein encoded by MIC2 gene is involved in multiple cellular events including cell adhesion and migration, apoptosis, cell differentiation and regulation of protein trafficking either in physiological or pathological conditions", "The surgical specimens showed small round cell tumor with positive staining for MIC2 gene product (CD99)", "We report 2 unusual cytogenetic findings in a pediatric Ewing sarcoma, an insertion of the MIC2 gene encoding CD99 from Xp to 10p and a submicroscopic deletion of the well-known tumor supressor gene KLF6", "MIC2, the gene encoding the CD99 antigen, is found in the pseudoautosomal region of both the X and Y chromosomes", "Immunohistochemical analysis showed weak to moderate and partial staining for MIC2 (CD99) and WT1, respectively", "Human CD99, which is encoded by the mic2 gene, is a ubiquitous 32 kDa transmembrane protein", "The leukocyte surface molecule CD99 is an integral membrane glycoprotein encoded by the E2/MIC2 gene", "The tumors displayed intense immunoreactivity in a membranous pattern for CD99, the cell surface glycoprotein encoded by the MIC2 gene", "Human CD99 is a 32-kDa cell surface protein that is encoded by the MIC2 gene localized to the PAR1", "MIC2, the gene encoding the CD99 antigen, is found in the pseudoautosomal region of both the X and Y chromosomes", "CD99, the product of the MIC2 gene, exhibits an erythroid-specific quantitative polymorphism co-regulated with the Xga blood group polymorphism" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/8399135", "http://www.ncbi.nlm.nih.gov/pubmed/24322504", "http://www.ncbi.nlm.nih.gov/pubmed/17725386", "http://www.ncbi.nlm.nih.gov/pubmed/15978751", "http://www.ncbi.nlm.nih.gov/pubmed/9623916", "http://www.ncbi.nlm.nih.gov/pubmed/10492040", "http://www.ncbi.nlm.nih.gov/pubmed/24158076", "http://www.ncbi.nlm.nih.gov/pubmed/1867320", "http://www.ncbi.nlm.nih.gov/pubmed/15359120", "http://www.ncbi.nlm.nih.gov/pubmed/10782405", "http://www.ncbi.nlm.nih.gov/pubmed/11037347", "http://www.ncbi.nlm.nih.gov/pubmed/10941840", "http://www.ncbi.nlm.nih.gov/pubmed/9278313", "http://www.ncbi.nlm.nih.gov/pubmed/22356523", "http://www.ncbi.nlm.nih.gov/pubmed/23644663", "http://www.ncbi.nlm.nih.gov/pubmed/21063743", "http://www.ncbi.nlm.nih.gov/pubmed/25007147", "http://www.ncbi.nlm.nih.gov/pubmed/22020966", "http://www.ncbi.nlm.nih.gov/pubmed/10688843" ]

[]

[ "http://www.uniprot.org/uniprot/CD99_HUMAN" ]

[ "Popular programs for transcript quantification from RNASeq experiments include: Cufflinks, RSEM, Flux Capacitor, Mitie, Miso, Tigar, Montebello, Drut, Traph, Pome, IsoformEx, Neuma," ]

[ "Cufflinks", "RSEM", "Flux Capacitor", "Mitie", "Miso", "Tigar", "Montebello", "Drut", "Traph", "Pome", "IsoformEx", "Neuma" ]

[ "Splicing Analysis Kit (Spanki", "ORMAN ( O ptimal R esolution of M ultimapping A mbiguity of R N A-Seq Reads), which aims to compute the minimum number of potential transcript products for each gene and to assign each multimapping read to one of these transcripts based on the estimated distribution of the region covering the read.", "MITIE (Mixed Integer Transcript IdEntification) for simultaneous transcript reconstruction and quantification.", "Montebello, an integrated statistical approach which performs simultaneous isoform discovery and quantification by using a Monte Carlo simulation to find the most likely isoform composition", "IGAR: transcript isoform abundance estimation method with gapped alignment of RNA-Seq data", "a statistical method to estimate transcript isoform abundances from RNA-Seq data.", "RNA-Seq data with TopHat and Cufflinks", "Experimental results on prediction accuracy show that our method is very competitive with popular tools such as Cufflinks and IsoLasso. Our tool, called Traph", "By resolving the linear system with LASSO, our approach can infer an accurate set of dominantly expressed transcripts while existing methods tend to assign positive expression to every candidate isoform", "the Minimum Unique Length Tool (MULTo), a framework for efficient and comprehensive representation of mappability information, through identification of the shortest possible length required for each genomic coordinate to become unique in the genome and transcriptome", " a pipeline for processing and analyzing RNA-Seq data, that we have named Grape (Grape RNA-Seq Analysis Pipeline Environment)", "Our method, referred as Discovery and Reconstruction of Unannotated Transcripts (DRUT), can be used to enhance existing transcriptome assemblers, such as Cufflinks, as well as to accurately estimate the transcript frequencies", "DiffSplice", "Omicsoft sequence aligner (OSA), a fast and accurate alignment tool for RNA-Seq data.", " two popular tools for isoform quantification, MISO and Cufflinks", " The method is implemented in the seqbias R/Bioconductor package, available freely under the LGPL license", "Poisson mixed-effects (POME) model to characterize base-level read coverage within each transcript", "SpliceTrap, a method to quantify exon inclusion levels using paired-end RNA-seq data", "We present RSEM, an user-friendly software package for quantifying gene and isoform abundances from single-end or paired-end RNA-Seq data", "We propose a novel algorithm (IsoformEx) that employs weighted non-negative least squares estimation method to estimate the expression levels of transcript isoforms.", "Rnnotator, an automated software pipeline that generates transcript models by de novo assembly of RNA-Seq data without the need for a reference genome", "Here we introduce such algorithms in an open-source software program called Cufflinks.", "propose a novel, efficient and intuitive approach of estimating mRNA abundances from the whole transcriptome shotgun sequencing (RNA-Seq) data. Our method, NEUMA (Normalization by Expected Uniquely Mappable Area), is based on effective length normalization using uniquely mappable areas of gene and mRNA isoform models." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/20436464", "http://www.ncbi.nlm.nih.gov/pubmed/24209455", "http://www.ncbi.nlm.nih.gov/pubmed/21896509", "http://www.ncbi.nlm.nih.gov/pubmed/23616006", "http://www.ncbi.nlm.nih.gov/pubmed/23888185", "http://www.ncbi.nlm.nih.gov/pubmed/23821651", "http://www.ncbi.nlm.nih.gov/pubmed/23349747", "http://www.ncbi.nlm.nih.gov/pubmed/22537040", "http://www.ncbi.nlm.nih.gov/pubmed/21816040", "http://www.ncbi.nlm.nih.gov/pubmed/22072384", "http://www.ncbi.nlm.nih.gov/pubmed/24130305", "http://www.ncbi.nlm.nih.gov/pubmed/21106091", "http://www.ncbi.nlm.nih.gov/pubmed/22285831", "http://www.ncbi.nlm.nih.gov/pubmed/21059678", "http://www.ncbi.nlm.nih.gov/pubmed/21794104", "http://www.ncbi.nlm.nih.gov/pubmed/23980025", "http://www.ncbi.nlm.nih.gov/pubmed/23329413", "http://www.ncbi.nlm.nih.gov/pubmed/23155066", "http://www.ncbi.nlm.nih.gov/pubmed/23461570", "http://www.ncbi.nlm.nih.gov/pubmed/23202426", "http://www.ncbi.nlm.nih.gov/pubmed/23734627", "http://www.ncbi.nlm.nih.gov/pubmed/22592379" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D017423" ]

[ "In 1992, Brugada and Brugada first described a new entity, which became known as Brugada syndrome, that is associated with a high risk of ventricular arrhythmias and sudden cardiac death in patients without structural heart disease. This syndrome is characterized by a distinct electrocardiographic phenotype, type 1 Brugada pattern, consisting of a coved ST-segment elevation (≥0.2 mV) followed by a negative T wave in more than one right precordial lead. The typical Brugada electrocardiogram (ECG) phenotype is often concealed in affected population. Brugada syndrome is a genetically determined familial disease with autosomal dominant transmission and variable penetrance, conferring a predisposition to sudden cardiac death due to ventricular arrhythmias. Brugada syndrome (BrS)is considered to be a primary inherited channelopathy often involving the inward sodium current and the diagnosis has traditionally required the exclusion of overt structural heart disease. Brugada syndrome (BrS) is an inherited cardiac disease characterized by ST segment elevation in V1-V3 ECG leads. Mutations SCN5A gene encoding for the cardiac voltage-gated Na(+) channel are found in some BrS patients, but also in family members with isolated conduction disturbances." ]

[]

[ "In 1992, Brugada and Brugada first described a new entity, which became known as Brugada syndrome, that is associated with a high risk of ventricular arrhythmias and sudden cardiac death in patients without structural heart disease. This syndrome is characterized by a distinct electrocardiographic phenotype, type 1 Brugada pattern, consisting of a coved ST-segment elevation (≥0.2 mV) followed by a negative T wave in more than one right precordial lead.", "Brugada syndrome predisposes individuals to ventricular arrhythmias and sudden cardiac death, in the absence of structural heart disease. The typical Brugada electrocardiogram (ECG) phenotype is often concealed in affected population", "Brugada syndrome is a rare cardiac arrhythmia characterized by electrocardiographic right bundle branch block and persistent ST-segment elevation in the right precordial leads.", "Brugada syndrome is a genetically determined familial disease with autosomal dominant transmission and variable penetrance, conferring a predisposition to sudden cardiac death due to ventricular arrhythmias.", "Brugada syndrome (BrS) ", "BrS is considered to be a primary inherited channelopathy often involving the inward sodium current and the diagnosis has traditionally required the exclusion of overt structural heart disease. ", "Brugada syndrome (BrS) primarily associates with the loss of sodium channel function.", "PKP2 mutations may be a molecular substrate leading to the diagnosis of BrS.", "Brugada syndrome is an inherited arrhythmia syndrome predisposing to sudden cardiac death. ", "the first mutations in SCN5A encoding the cardiac sodium channel Nav1.5 were reported.", "Brugada syndrome is characterized by typical ECG features, ventricular arrhythmias and sudden cardiac death (SCD), more frequent during nighttime.", "Brugada syndrome (BrS) is an inherited cardiac disease characterized by ST segment elevation in V1-V3 ECG leads. Mutations SCN5A gene encoding for the cardiac voltage-gated Na(+) channel are found in some BrS patients, but also in family members with isolated conduction disturbances.", "Brugada syndrome (BrS), one of the most frequently diagnosed inherited arrhythmogenic syndromes, is responsible for more than 4% of all sudden deaths and at least 20% of sudden deaths in patients with structurally normal hearts.", "Brugada syndrome is a major cause of sudden death in young adults.", "Brugada's syndrome is one of the main causes of sudden death in young adults without a structural heart disease", "The Brugada syndrome is a clinical-electrocardiographic diagnosis characterized by syncopal episodes or sudden death (caused by ventricular tachycardia and ventricular fibrillation) in patients with a structurally normal heart with a characteristic electrocardiographic pattern consisting of ST segment elevation in precordial leads (Vl-V3) and a morphology of the QRS complex resembling right bundle branch block (the latter can transiently disappear). Timely diagnosis and adequate treatment may essentially decrease mortality of this disease.", "Brugada syndrome", "In 1992 we described a new syndrome consisting of syncopal episodes and/or sudden death in patients with a structurally normal heart and a characteristic electrocardiogram displaying a pattern resembling right bundle branch block with an ST segment elevation in leads V1 to V3. In 1998 it was described that the disease is genetically determined with an autosomal dominant pattern of transmission. Three different mutations have been identified. All three mutations affect the structure and the function of the sodium channel SCN5A.", "The diagnosis is easily made by means of the electrocardiogram (ECG). The presence of concealed and intermittent forms, however, makes the diagnosis difficult in some patients.", "The Brugada syndrome is a clinical-electrocardiographic diagnosis characterised by syncopal or sudden death episodes in patients with a structurally normal heart with a characteristic electrocardiographic pattern consisting of ST segment elevation in the precordial leads V1 to V3 and a morphology of the QRS complex resembling a right bundle branch block. In many patients with the Brugada syndrome, the electrocardiographic manifestations transiently normalize; leading to underdiagnosis of the syndrome. ", "The incidence of sudden death in this syndrome is very high and can only be prevented by implanting a cardioverter-defibrillator. " ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/23905889", "http://www.ncbi.nlm.nih.gov/pubmed/14671564", "http://www.ncbi.nlm.nih.gov/pubmed/24827804", "http://www.ncbi.nlm.nih.gov/pubmed/25187091", "http://www.ncbi.nlm.nih.gov/pubmed/23669108", "http://www.ncbi.nlm.nih.gov/pubmed/22559801", "http://www.ncbi.nlm.nih.gov/pubmed/10443304", "http://www.ncbi.nlm.nih.gov/pubmed/24405173", "http://www.ncbi.nlm.nih.gov/pubmed/25448794", "http://www.ncbi.nlm.nih.gov/pubmed/10959460", "http://www.ncbi.nlm.nih.gov/pubmed/22451857", "http://www.ncbi.nlm.nih.gov/pubmed/23612926", "http://www.ncbi.nlm.nih.gov/pubmed/11892423", "http://www.ncbi.nlm.nih.gov/pubmed/24932359", "http://www.ncbi.nlm.nih.gov/pubmed/24352520" ]

[]

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

[ "Parkinson's disease (PD) is characterized by the progressive degeneration of substantia nigra pars compacta (SNpc) dopaminergic neurones and the formation of Lewy bodies (LB) in a proportion of the remaining neurones. Alpha-synuclein has been identified as the main component of the Lewy bodies.", "The main component of Lewy bodies is alpha-synuclein.", "Parkinson s disease (PD) is one of the most common neurodegenerative diseases. Majority of PD are sporadic, for which genetic causes remain largely unknown. Alpha-synuclein, the main component of Lewy bodies, plays a central role in the PD pathogenesis " ]

[ "Alpha-synuclein" ]

[ "α-syn is the main component of Lewy bodies in Parkinson's disease (PD) and Lewy body dementia", "Parkinson's disease (PD) is one of the most common neurodegenerative diseases. Majority of PD are sporadic, for which genetic causes remain largely unknown. Alpha-synuclein, the main component of Lewy bodies, plays a central role in the PD pathogenesis", "Parkinson's disease (PD) is characterized by the progressive degeneration of substantia nigra pars compacta (SNpc) dopaminergic neurones and the formation of Lewy bodies (LB) in a proportion of the remaining neurones. α-synuclein is the main component of LB, but the pathological mechanisms that lead to neurodegeneration associated with LB formation remain unclear", "α-Synuclein is the main component of Lewy bodies, the intraneuronal inclusion bodies characteristic of Parkinson's disease", "Parkinson's disease (PD) is the second most common neurodegenerative disease. The majority of PD cases are sporadic, for which genetic causes and underlying molecular mechanisms remain largely unclear. Autophagy, a highly conserved cellular process that governs the breakdown of long-lived proteins and organelles, has been involved in the degradation of α-synuclein (α-Syn), the main component of Lewy bodies", "The main component of Lewy bodies is alpha-synuclein", "Alpha-synuclein, a main component of Lewy bodies in synucleinopathies and senile plaques in Alzheimer disease, is centrally involved in neurodegeneration", "alpha-Synuclein, the main component of LBs, is expressed as two main isoforms (112 and 140), but little is known about their differential expression in the brain. ", "Amyloid precursor protein (APP) is involved in the accumulation of alpha-synuclein, the main component of Lewy bodies", "The pre-synaptic protein alpha-synuclein is the main component of Lewy bodies and Lewy neurites, the defining neuropathological characteristics of Parkinson's disease and dementia with Lewy bodies.", "Specifically, identification of Lewy bodies in fetal mesencephalic neurons transplanted in patients with Parkinson's disease raised the hypothesis that α-synuclein, the main component of Lewy bodies, could be transmitted from the host brain to a graft of healthy neurons.", "LBD has neuropathological characteristics whereby numerous Lewy bodies are present in the central and sympathetic nervous systems, and it is a type of alpha-synucleinopathy because the main component of Lewy body is alpha-synuclein.", "In Parkinson's disease, the inclusion bodies are referred to as Lewy bodies and their main component is alpha-synuclein.", "The main component of Lewy bodies is alpha-synuclein.", "The main component of Lewy bodies is alpha-synuclein (AS).", "Amyloid precursor protein (APP) is involved in the accumulation of alpha-synuclein, the main component of Lewy bodies.", "Alpha-synuclein, a main component of Lewy bodies in synucleinopathies and senile plaques in Alzheimer disease, is centrally involved in neurodegeneration.", "�-Synuclein is the main component of Lewy bodies, the intraneuronal inclusion bodies characteristic of Parkinsons disease.", "In the 1990s, �-synuclein was identified as the main constituent of the Lewy pathology, and its aggregation was shown to be central to PD, dementia with Lewy bodies, and multiple system atrophy.", "Identification of protein interfaces between �-synuclein, the principal component of Lewy bodies in Parkinson disease, and the molecular chaperones human Hsc70 and the yeast Ssa1p.", "Fibrillar �-synuclein (�-Syn) is the principal component of Lewy bodies, which are evident in individuals affected by Parkinson disease (PD).", "�-Synuclein is a major component of Lewy bodies in Parkinson disease (PD) and dementia with Lewy bodies (DLB).", "The main component of Lewy bodies is alpha-synuclein.", "In Parkinson's disease, the inclusion bodies are referred to as Lewy bodies and their main component is alpha-synuclein.", "Specifically, identification of Lewy bodies in fetal mesencephalic neurons transplanted in patients with Parkinson's disease raised the hypothesis that α-synuclein, the main component of Lewy bodies, could be transmitted from the host brain to a graft of healthy neurons.", "alpha-Synuclein, the main component of LBs, is expressed as two main isoforms (112 and 140), but little is known about their differential expression in the brain.", "In Parkinson's disease and Lewy body dementia, alpha-synuclein is the main component of Lewy bodies and dystrophic neurites; alpha-synuclein also accumulates in the cytoplasm of glial cells", "In Parkinson's disease, the inclusion bodies are referred to as Lewy bodies and their main component is alpha-synuclein", "The main component of Lewy bodies is alpha-synuclein (AS)", "Specifically, identification of Lewy bodies in fetal mesencephalic neurons transplanted in patients with Parkinson's disease raised the hypothesis that α-synuclein, the main component of Lewy bodies, could be transmitted from the host brain to a graft of healthy neurons", "alpha-Synuclein, the main component of LBs, is expressed as two main isoforms (112 and 140), but little is known about their differential expression in the brain", "alpha-Synuclein and ubiquitin are two Lewy body protein components that may play antagonistic roles in the pathogenesis of Lewy bodies", "Recently, the presynaptic protein alpha-synuclein was shown to be a major component of Lewy bodies and Lewy neurites", "Alpha-synuclein (AS) is the main component of Lewy bodies and its aggregation is a key event in the pathogenesis of PD", "The therapeutical potential of alpha-synuclein antiaggregatory agents for dementia with Lewy bodies." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/23300799", "http://www.ncbi.nlm.nih.gov/pubmed/23295909", "http://www.ncbi.nlm.nih.gov/pubmed/15541000", "http://www.ncbi.nlm.nih.gov/pubmed/20534649", "http://www.ncbi.nlm.nih.gov/pubmed/22923347", "http://www.ncbi.nlm.nih.gov/pubmed/11412709", "http://www.ncbi.nlm.nih.gov/pubmed/20846907", "http://www.ncbi.nlm.nih.gov/pubmed/16969096", "http://www.ncbi.nlm.nih.gov/pubmed/18991634", "http://www.ncbi.nlm.nih.gov/pubmed/23183883", "http://www.ncbi.nlm.nih.gov/pubmed/10327208", "http://www.ncbi.nlm.nih.gov/pubmed/21683963", "http://www.ncbi.nlm.nih.gov/pubmed/21937912", "http://www.ncbi.nlm.nih.gov/pubmed/23382946", "http://www.ncbi.nlm.nih.gov/pubmed/22843682", "http://www.ncbi.nlm.nih.gov/pubmed/15530662", "http://www.ncbi.nlm.nih.gov/pubmed/23562579", "http://www.ncbi.nlm.nih.gov/pubmed/23384565", "http://www.ncbi.nlm.nih.gov/pubmed/11085897", "http://www.ncbi.nlm.nih.gov/pubmed/16951579", "http://www.ncbi.nlm.nih.gov/pubmed/24597591" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016631", "http://www.disease-ontology.org/api/metadata/DOID:12217", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D020961" ]

[ "T4 increases myocardial mitochondrial bioenergetic capacity, oxygen consumption and markers of mitochondrial biogenesis. The marked, parallel increases in PPARalpha levels suggest its potential involvement in mediating myocardial-specific remodeling of mitochondria in response to T4. T3 induces mitochondrial biogenesis. In fact, T3 treatment for 72h increases activity of respiratory complexes II, IV, V and citrate synthase (CS), levels of mitochondrial enzyme subunits (e.g. COXI, COXIV) and nuclear-encoded transcription factors, involved in mitochondrial biogenesis (e.g. PGC-1, mtTFA and PPAR-alpha). Furthermore, L-T3 increases the expression of factors involved in mitochondrial DNA transcription and biogenesis, such as hypoxic inducible factor-1α, mitochondrial transcription factor A and peroxisome proliferator activated receptor γ coactivator-1α, in the LV peri-infarct zone.\nThe activation of TFAM and TFB2M expression is shown to be required for the induction of mtDNA biogenesis by T3. Truncated forms of the nuclear receptor TRα1, with molecular weights of 43 kDa (p43) and 28 Kda have been previously identified in mitochondria. P43 is a mitochondrial T3 receptor which stimulates mitochondrial transcription and protein synthesis in the presence of T3. p43 depletion in mice decreases mitochondrial DNA replication and respiratory chain activity." ]

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[ "L-T3 significantly increased the expression of factors involved in mitochondrial DNA transcription and biogenesis, such as hypoxic inducible factor-1α, mitochondrial transcription factor A and peroxisome proliferator activated receptor γ coactivator-1α, in the LV peri-infarct zone", "the T(3)-induced phosphorylation of p38 and AMPK in both slow- and fast-twitch skeletal muscles suggests that these events may be important in mediating hormone-induced increases in mitochondrial biogenesis in skeletal muscle.", "Our findings indicate parallel increases in myocardial mitochondrial bioenergetic capacity, oxygen consumption and markers of mitochondrial biogenesis with 15-day T4", "The marked, parallel increases in PPARalpha levels suggest its potential involvement in mediating myocardial-specific remodeling of mitochondria in response to T4", "T3 mediates an early stimulation of enzymes containing mtDNA encoded subunits (e.g. complex IV and V) in contrast to a different regulatory pattern for the entirely nuclear-encoded enzymes", "Activity of respiratory complexes II, IV, V and citrate synthase (CS), levels of mitochondrial enzyme subunits (e.g. COXI, COXIV) and nuclear-encoded transcription factors, involved in mitochondrial biogenesis (e.g. PGC-1, mtTFA and PPAR-alpha), were significantly elevated with 72 h T3 treatment", "T(3) increased PGC-1alpha content similarly in both fast- and slow-twitch muscle, as well as in the liver, but not in heart.", "Thyroid hormone [3,5,3'-triiodo-l-thyronine (T(3))] induces phenotypic alterations in cardiac mitochondria, in part by influencing protein import and the expression of the import motor mitochondrial heat shock protein (mtHsp70).", "These findings indicate that import machinery components are differentially regulated in response to stimuli that induce mitochondrial biogenesis, like T(3) and differentiation.", "We have previously identified a mitochondrial triiodothyronine receptor (p43) regulating mitochondrial transcription and mitochondrial biogenesis. When overexpressed in skeletal muscle, it increases mitochondrial DNA content, stimulates mitochondrial respiration,", "Here we show that a p43 depletion in mice decreases mitochondrial DNA replication and respiratory chain activity in skeletal muscle", "The contribution of TFAM, TFB2M, and helicase Twinkle in thyroid-induced mtDNA biogenesis was assessed. The activation of TFAM and TFB2M expression is shown to be required for the induction of mtDNA biogenesis. The role of helicase Twinkle, the expression induction of which is also observed after triiodothyronine addition, remains unclear. The analysis of factors that activate TFAM and TFB2M expression showed that NRF-1 is the determinative regulator:", "in rat cerebellum show that hypothyroidism causes reduction in expression of nuclear encoded genes controlling mitochondrial biogenesis like PGC-1alpha, NRF-1alpha and Tfam", "These results thus indicate an integrated nuclear-mitochondrial cross talk in regulation of mitochondrial transcription by TH during brain development.", "T(3) acts to reduce cellular oxidative stress, which may help attenuate ROS-mediated damage, along with improving mitochondrial function and energy status in cells with mtDNA defects.", "These findings suggest the existence of compensatory mechanisms operating at the translational and/or post-translational levels which promote proliferation of mitochondria in the hypothyroid liver. However, when the liver mass was considered, hypothyroidism significantly reduced overall mitochondrial proliferation in rat liver.", "Total liver mitochondrial DNA levels in thyroid-treated animals were greater than age-paired controls by 79% at 7 days but only 67% at 14 days since a small gain occurred in control animals and no further increase occurred in treated rats during the second week.", "thyroid hormone treatment produces hyperplasia and an increase in mitochondrial number and mass in rat liver", "It is concluded that T3 exerts a direct, rather than permissive, effect on mitochondrial biogenesis, and that high affinity binding sites for GH are not present in rat liver mitochondria.", "These data strengthen the view that thyroid hormone regulates synthesis of specific components within each respiratory-chain complex and that these products apparently play key roles in inner-membrane biogenesis and assembly", "It is concluded that thyroid hormone causes an increase in the mitochondrial mass, mitochondrial cytochrome content, and respiratory rate, and consequently expands the capacity of oxidative metabolism without an uncoupling effect on oxidative phosphorylation." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/15543939", "http://www.ncbi.nlm.nih.gov/pubmed/17962579", "http://www.ncbi.nlm.nih.gov/pubmed/2773621", "http://www.ncbi.nlm.nih.gov/pubmed/12388124", "http://www.ncbi.nlm.nih.gov/pubmed/215035", "http://www.ncbi.nlm.nih.gov/pubmed/19462004", "http://www.ncbi.nlm.nih.gov/pubmed/20100314", "http://www.ncbi.nlm.nih.gov/pubmed/21568860", "http://www.ncbi.nlm.nih.gov/pubmed/7556180", "http://www.ncbi.nlm.nih.gov/pubmed/22109994", "http://www.ncbi.nlm.nih.gov/pubmed/12734114", "http://www.ncbi.nlm.nih.gov/pubmed/19036942", "http://www.ncbi.nlm.nih.gov/pubmed/1321044", "http://www.ncbi.nlm.nih.gov/pubmed/15893763", "http://www.ncbi.nlm.nih.gov/pubmed/21914860", "http://www.ncbi.nlm.nih.gov/pubmed/20515651", "http://www.ncbi.nlm.nih.gov/pubmed/18575627", "http://www.ncbi.nlm.nih.gov/pubmed/6157679" ]

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[ "http://www.uniprot.org/uniprot/THB_SHEEP", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013963", "http://www.uniprot.org/uniprot/THA_APTPA", "http://www.uniprot.org/uniprot/THB_CAIMO", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009206", "http://www.uniprot.org/uniprot/THA_CAIMO", "http://www.uniprot.org/uniprot/THB_LITCT", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011988", "http://www.uniprot.org/uniprot/THBA_XENLA", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0070324", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0070327", "http://www.uniprot.org/uniprot/THB_PAROL", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D037021", "http://www.uniprot.org/uniprot/THB_DANRE", "http://www.uniprot.org/uniprot/THB_RAT", "http://www.uniprot.org/uniprot/THAA_DANRE", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0010861", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0046966", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0002154", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013974", "http://www.uniprot.org/uniprot/THB_HUMAN", "http://www.biosemantics.org/jochem#4250045", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D037042", "http://www.uniprot.org/uniprot/THB_CHICK", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0004887", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D008929", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D008928", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0006590", "http://www.uniprot.org/uniprot/THA_SALSA", "http://www.uniprot.org/uniprot/THB_MOUSE" ]

[ "Most HOT regions co-localize with RNA polymerase II binding sites, but many are not near the promoters of annotated genes. At HOT promoters, TF occupancy is strongly predictive of transcription preinitiation complex recruitment and moderately predictive of initiating Pol II recruitment, but only weakly predictive of elongating Pol II and RNA transcript abundance." ]

[ "Transcription-factor occupancy at HOT regions quantitatively predicts RNA polymerase recruitment." ]

[ "Transcription-factor occupancy at HOT regions quantitatively predicts RNA polymerase recruitment in five human cell lines.", "Most HOT regions co-localize with RNA polymerase II binding sites, but many are not near the promoters of annotated genes. At HOT promoters, TF occupancy is strongly predictive of transcription preinitiation complex recruitment and moderately predictive of initiating Pol II recruitment, but only weakly predictive of elongating Pol II and RNA transcript abundance.", "CONCLUSIONS: Mammalian HOT regions are regulatory hubs that integrate the signals from diverse regulatory pathways to quantitatively tune the promoter for RNA polymerase II recruitment.", "We identified HOT regions by a comprehensive analysis of ChIP-seq data from 96 DNA-associated proteins in 5 human cell lines. Most HOT regions co-localize with RNA polymerase II binding sites, but many are not near the promoters of annotated genes.", "Most HOT regions co-localize with RNA polymerase II binding sites, but many are not near the promoters of annotated genes. At HOT promoters, TF occupancy is strongly predictive of transcription preinitiation complex recruitment and moderately predictive of initiating Pol II recruitment, but only weakly predictive of elongating Pol II and RNA transcript abundance.", "At HOT promoters, TF occupancy is strongly predictive of transcription preinitiation complex recruitment and moderately predictive of initiating Pol II recruitment, but only weakly predictive of elongating Pol II and RNA transcript abundance. TF occupancy varies quantitatively within human HOT regions; we used this variation to discover novel associations between TFs.", "Mammalian HOT regions are regulatory hubs that integrate the signals from diverse regulatory pathways to quantitatively tune the promoter for RNA polymerase II recruitment.", "We identified HOT regions by a comprehensive analysis of ChIP-seq data from 96 DNA-associated proteins in 5 human cell lines. Most HOT regions co-localize with RNA polymerase II binding sites, but many are not near the promoters of annotated genes.", "Mammalian HOT regions are regulatory hubs that integrate the signals from diverse regulatory pathways to quantitatively tune the promoter for RNA polymerase II recruitment." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/24138567" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012320", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012318", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012319", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012321" ]

[ "V60L\nD84E\nV92M\nR151C\nR160W\nR163Q\nD294H" ]

[ "V60L", "D84E", "V92M", "R151C", "R160W", "R163Q", "D294H" ]

[ "All of the investigated variants showed positive associations with NMSC, with consistent significant results obtained for V60L, D84E, V92M, R151C, R160W, R163Q and D294H: SOR (95%CI) ranged from 1.42 (1.19-1.70) for V60L to 2.66 (1.06-6.65) for D84E variant.", "The melanocortin 1 receptor (MC1R) gene encodes for a seven-pass transmembrane receptor primarily expressed on melanocytes and melanoma cells.", "for V60L to 2.74 (1.53-4.89) for D84E. ", " We aim to examine the influence of the MC1R variants (RHC: D84E, R151C, R160W; NRHC: V60L, R163Q and the synonymous polymorphism T314T) on the MM risk in a population from the Canary Islands. " ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/24170137", "http://www.ncbi.nlm.nih.gov/pubmed/25219681", "http://www.ncbi.nlm.nih.gov/pubmed/26103569", "http://www.ncbi.nlm.nih.gov/pubmed/24917043" ]

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[]

[ "The removal of the 5'-cap structure by the decapping enzyme DCP2 and its coactivator DCP1 shuts down translation and exposes the mRNA to 5'-to-3' exonucleolytic degradation by XRN1", "The removal of the 5'-cap structure by the decapping enzyme DCP2 and its coactivator DCP1 shuts down translation and exposes the mRNA to 5'-to-3' exonucleolytic degradation by XRN1." ]

[ "XRN1" ]

[ "The removal of the 5'-cap structure by the decapping enzyme DCP2 and its coactivator DCP1 shuts down translation and exposes the mRNA to 5'-to-3' exonucleolytic degradation by XRN1", "DCP2 activation by DCP1 occurs preferentially on the EDC4 scaffold, which may serve to couple DCP2 activation by DCP1 with 5'-to-3' mRNA degradation by XRN1 in human cells", "XRN1 is a 5' → 3' processive exoribonuclease that degrades mRNAs after they have been decapped" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/24510189", "http://www.ncbi.nlm.nih.gov/pubmed/22383165" ]

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[]

[ "Heterozygous mutations in the Berardinelli-Seip congenital lipodystrophy (BSCL2) gene have been associated with different clinical phenotypes including Silver syndrome/spastic paraplegia 17, distal hereditary motor neuropathy type V, and Charcot-Marie-Tooth disease type 2 (CMT2) with predominant hand involvement.", "Heterozygous mutations in the Berardinelli-Seip congenital lipodystrophy (BSCL2) gene have been associated with different clinical phenotypes including Silver syndrome/spastic paraplegia 17, distal hereditary motor neuropathy type V, and Charcot-Marie-Tooth disease type 2 (CMT2) with predominant hand involvement" ]

[ "Silver syndrome/spastic paraplegia 17", "Distal hereditary motor neuropathy type V", "Charcot-Marie-Tooth disease type 2 (CMT2) with predominant hand involvement" ]

[ "Heterozygous mutations in the Berardinelli-Seip congenital lipodystrophy (BSCL2) gene have been associated with different clinical phenotypes including Silver syndrome/spastic paraplegia 17, distal hereditary motor neuropathy type V, and Charcot-Marie-Tooth disease type 2 (CMT2) with predominant hand involvement", "Distal hereditary motor neuropathy type V (dHMN-V) and Charcot-Marie-Tooth syndrome (CMT) type 2 presenting with predominant hand involvement, also known as CMT2D and Silver syndrome (SS) are rare phenotypically overlapping diseases which can be caused by mutations in the Berardinelli-Seip Congenital Lipodystrophy 2 (BSCL2) and in the glycyl-tRNA synthetase encoding (GARS) genes", "Heterozygous mutations in the Berardinelli-Seip congenital lipodystrophy (BSCL2) gene have been associated with different clinical phenotypes including Silver syndrome/spastic paraplegia 17, distal hereditary motor neuropathy type V, and Charcot-Marie-Tooth disease type 2 (CMT2) with predominant hand involvement.", "In 2004, heterozygous mutations (N88S, S90L) in the Seipin/BSCL2 gene were identified in two autosomal dominant motor neuron diseases, distal hereditary motor neuropathy type V (OMIM #182960) and Silver syndrome (OMIM #270685).", "We recently found heterozygous mutations in the Berardinelli-Seip congenital lipodystrophy (BSCL2, seipin) gene causing SPG17 and distal hereditary motor neuropathy type V (distal HMN V).", "Distal hereditary motor neuropathy type V (dHMN-V) and Silver syndrome are rare phenotypically overlapping diseases which can be caused by mutations in the Berardinelli-Seip Congenital Lipodystrophy 2 (BSCL2) gene or Seipin.", "Heterozygous missense mutations in BSCL2 are associated with distal hereditary motor neuropathy and Silver syndrome.", "Heterozygous mutations in the Seipin/BSCL2 gene have recently been identified in two autosomal dominant motor neuron diseases, distal hereditary motor neuropathy type V and Silver's syndrome.", "We recently found heterozygous mutations in the Berardinelli-Seip congenital lipodystrophy (BSCL2, seipin) gene causing SPG17 and distal hereditary motor neuropathy type V (distal HMN V)", "Heterozygous missense mutations in BSCL2 are associated with distal hereditary motor neuropathy and Silver syndrome", "In 2004, heterozygous mutations (N88S, S90L) in the Seipin/BSCL2 gene were identified in two autosomal dominant motor neuron diseases, distal hereditary motor neuropathy type V (OMIM #182960) and Silver syndrome (OMIM #270685)", "Heterozygous mutations in the Berardinelli-Seip congenital lipodystrophy (BSCL2) gene have been associated with different clinical phenotypes including Silver syndrome/spastic paraplegia 17, distal hereditary motor neuropathy type V, and Charcot-Marie-Tooth disease type 2 (CMT2) with predominant hand involvement. ", "Heterozygous mutations in the Berardinelli-Seip congenital lipodystrophy (BSCL2) gene have been associated with different clinical phenotypes including Silver syndrome/spastic paraplegia 17,", "We recently found heterozygous mutations in the Berardinelli-Seip congenital lipodystrophy (BSCL2, seipin) gene causing SPG17 and distal hereditary motor neuropathy type V (distal HMN V). Here we report the clinical features of two families with heterozygous BSCL2 mutations.", "Heterozygous mutations in the Berardinelli-Seip congenital lipodystrophy (BSCL2) gene have been associated with different clinical phenotypes including Silver syndrome/spastic paraplegia 17, distal hereditary motor neuropathy type V, and Charcot-Marie-Tooth disease type 2 (CMT2) with predominant hand involvement.", "Heterozygous missense mutations in BSCL2 are associated with distal hereditary motor neuropathy and Silver syndrome.", "We recently found heterozygous mutations in the Berardinelli-Seip congenital lipodystrophy (BSCL2, seipin) gene causing SPG17 and distal hereditary motor neuropathy type V (distal HMN V).", "In 2004, heterozygous mutations (N88S, S90L) in the Seipin/BSCL2 gene were identified in two autosomal dominant motor neuron diseases, distal hereditary motor neuropathy type V (OMIM #182960) and Silver syndrome (OMIM #270685).", "Heterozygous mutations in the Seipin/BSCL2 gene have recently been identified in two autosomal dominant motor neuron diseases, distal hereditary motor neuropathy type V and Silver's syndrome." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/17387721", "http://www.ncbi.nlm.nih.gov/pubmed/20598714", "http://www.ncbi.nlm.nih.gov/pubmed/17633104", "http://www.ncbi.nlm.nih.gov/pubmed/14981520", "http://www.ncbi.nlm.nih.gov/pubmed/20806400", "http://www.ncbi.nlm.nih.gov/pubmed/17663003", "http://www.ncbi.nlm.nih.gov/pubmed/15242882" ]

[]

[]

[ "Nivolumab was developed as a monoclonal antibody against programmed death receptor-1, an immune checkpoint inhibitor which negatively regulates T-cell proliferation and activation." ]

[ "programmed death receptor-1" ]

[ "nivolumab, a fully human IgG4 programmed death 1 (PD-1) immune-checkpoint-inhibitor antibody", " Nivolumab (a programmed death 1 [PD-1] checkpoint inhibitor)", "Nivolumab, a fully human immunoglobulin G4 programmed death 1 immune checkpoint inhibitor antibody, ", " programmed death receptor-1 (PD-1) inhibitors pembrolizumab and nivolumab were approved for the treatment of advanced melanoma", "Nivolumab was developed as a monoclonal antibody against programmed death receptor-1, an immune checkpoint inhibitor which negatively regulates T-cell proliferation and activation. ", "Nivolumab, a programmed death 1 (PD-1) checkpoint inhibitor," ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/26028407", "http://www.ncbi.nlm.nih.gov/pubmed/26448890", "http://www.ncbi.nlm.nih.gov/pubmed/26273207", "http://www.ncbi.nlm.nih.gov/pubmed/26027431", "http://www.ncbi.nlm.nih.gov/pubmed/25897158", "http://www.ncbi.nlm.nih.gov/pubmed/26406148" ]

[]

[]

[ "There are numerous CXCR2 receptor antagonists, such as SB225002, G31P, SCH-527123, AZ10397767, SCH-479833." ]

[ "SB225002", "G31P", "SCH-527123", "AZ10397767", "SCH-479833" ]

[ "CXCR2 small-molecule antagonist (SB225002)", "G31P, an antagonist against CXC chemokine receptors 1 and 2, inhibits growth of human prostate cancer cells in nude mice.", "The CXCR2 antagonist, SCH-527123, shows antitumor activity", "retreatment with the CXCR2 antagonist AZ10397767", "The aim of this study was to investigate whether the CXCR2 antagonist, SCH-527123, inhibits colorectal cancer proliferation and if it can sensitize colorectal cancer cells to oxaliplatin both in vitro and in vivo.", "we report that targeting CXCR2 and CXCR1 activity using orally active small molecule antagonist (SCH-527123, SCH-479833) inhibits human colon cancer liver metastasis mediated by decreased neovascularization and enhanced malignant cell apoptosis.", "CXCR2-specific small molecule inhibitor (AZ10397767) to investigate the recruitment and function of human neutrophils in tumors" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/15623601", "http://www.ncbi.nlm.nih.gov/pubmed/19549892", "http://www.ncbi.nlm.nih.gov/pubmed/15805273", "http://www.ncbi.nlm.nih.gov/pubmed/22590561", "http://www.ncbi.nlm.nih.gov/pubmed/21328342", "http://www.ncbi.nlm.nih.gov/pubmed/19809428", "http://www.ncbi.nlm.nih.gov/pubmed/17634442", "http://www.ncbi.nlm.nih.gov/pubmed/18289803", "http://www.ncbi.nlm.nih.gov/pubmed/20967859", "http://www.ncbi.nlm.nih.gov/pubmed/23204236", "http://www.ncbi.nlm.nih.gov/pubmed/11700073", "http://www.ncbi.nlm.nih.gov/pubmed/20652010", "http://www.ncbi.nlm.nih.gov/pubmed/23019013", "http://www.ncbi.nlm.nih.gov/pubmed/16540656", "http://www.ncbi.nlm.nih.gov/pubmed/21670971", "http://www.ncbi.nlm.nih.gov/pubmed/18790747", "http://www.ncbi.nlm.nih.gov/pubmed/18780829", "http://www.ncbi.nlm.nih.gov/pubmed/22391039", "http://www.ncbi.nlm.nih.gov/pubmed/23359652", "http://www.ncbi.nlm.nih.gov/pubmed/12244149", "http://www.ncbi.nlm.nih.gov/pubmed/12753603", "http://www.ncbi.nlm.nih.gov/pubmed/19293256", "http://www.ncbi.nlm.nih.gov/pubmed/21035946" ]

[]

[ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0048019", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0006605", "http://www.uniprot.org/uniprot/CXCR2_HUMAN", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0045238", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0046817", "http://www.disease-ontology.org/api/metadata/DOID:162" ]

[ "The FAA (FANCA) gene contains 43 exons spanning approximately 80 kb. Exons range from 34 to 188 bp, whereas sequence analysis of the 5' region upstream of the putative transcription start site showed no obvious TATA and CAAT boxes, but did show a GC-rich region, typical of housekeeping genes." ]

[]

[ "In the present study we describe the genomic structure of the FAA gene. The gene contains 43 exons spanning approximately 80 kb as determined by the alignment of four cosmids and the fine localization of the first and the last exons in restriction fragments of these clones. Exons range from 34 to 188 bp", "Sequence analysis of the 5' region upstream of the putative transcription start site showed no obvious TATA and CAAT boxes, but did show a GC-rich region, typical of housekeeping genes" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/9169126" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D052217" ]

[ "SNORD116 is a small nucleolar (sno) RNA gene cluster (HBII-85) implicated as a major contributor the Prader-Willi phenotype. \nSNORD116 genes appears to be responsible for the major features of PWS. \nSNORD116 is a paternally expressed box C/D snoRNA gene cluster.\nThe mouse C/D box snoRNA MBII-85 (SNORD116) is processed into at least five shorter RNAs using processing sites near known functional elements of C/D box snoRNAs.\nSnord116 expression in the medial hypothalamus, particularly within nuclei that are part of feeding circuitry. High expression of Snord116 was evident in the paraventricular (PVN) and ventromedial (VMH) nuclei, but particularly prevalent in the arcuate nucleus (ARC) according to in situ hybridization. Snord116 expression level in ventral hypothalamic dissections including ARC was significantly greater (by 2-fold) than that in cortex; and its expression level in dorsal hypothalamic dissections including PVN was double that in cortex. The enhanced expression pattern of Snord116 in hypothalamic nuclei was observed at weaning and young adult stages, but less obvious neonatally when expression was significantly more widespread. Therefore the expression of Snord116 likely is regulated developmentally.\nSnord116del mice with paternally derived deletion lack expression of this snoRNA. They have early-onset postnatal growth deficiency, but normal fertility and lifespan. While pituitary structure and somatotrophs are normal, liver Igf1 mRNA is decreased. In cognitive and behavior tests, Snord116del mice are deficient in motor learning and have increased anxiety. Around three months of age, they develop hyperphagia, but stay lean on regular and high-fat diet. On reduced caloric intake, Snord116del mice maintain their weight better than wild-type littermates, excluding increased energy requirement as a cause of hyperphagia. Normal compensatory feeding after fasting, and ability to maintain body temperature in the cold indicate normal energy homeostasis regulation. Metabolic chamber studies reveal that Snord116del mice maintain energy homeostasis by altered fuel usage. Prolonged mealtime and increased circulating ghrelin indicate a defect in meal termination mechanism. Snord116del mice, the first snoRNA deletion animal model, reveal a novel role for a non-coding RNA in growth and feeding regulation." ]

[]

[ "Further analysis with array-CGH identified a mosaic 847 kb deletion in 15q11-q13, including SNURF-SNRPN, the snoRNA gene clusters SNORD116 (HBII-85), SNORD115, (HBII-52), SNORD109 A and B (HBII-438A and B), SNORD64 (HBII-13), and NPAP1 (C15ORF2).", "All three deletions included SNORD116, but only two encompassed parts of SNURF-SNRPN, implicating SNORD116 as the major contributor to the Prader-Willi phenotype. Our case adds further information about genotype-phenotype correlation and supports the hypothesis that SNORD116 plays a major role in the pathogenesis of Prader-Willi syndrome.", "Whereas loss of function of the SNORD116 genes appears to be responsible for the major features of PWS, the role of the other genes is less clear. ", "Small nucleolar (sno) RNAs are a group of small RNAs located in nucleoli that modulate chemical modifications and maturation of ribosomal or other RNAs. Recent data suggest that snoRNA Snord116 is important for the pathogenesis of Prader-Willi syndrome (PWS) characterized by hyperphagia and obesity. The current study was conducted to assess a potential cellular link between Snord116 and phenotypes of PWS. Data from mice revealed Snord116 expression in the medial hypothalamus, particularly within nuclei that are part of feeding circuitry. High expression of Snord116 was evident in the paraventricular (PVN) and ventromedial (VMH) nuclei, but particularly prevalent in the arcuate nucleus (ARC) according to in situ hybridization. Snord116 expression level in ventral hypothalamic dissections including ARC was significantly greater (by 2-fold) than that in cortex; and its expression level in dorsal hypothalamic dissections including PVN was double that in cortex. The enhanced expression pattern of Snord116 in hypothalamic nuclei was observed at weaning and young adult stages, but less obvious neonatally when expression was significantly more widespread. Therefore the expression of Snord116 likely is regulated developmentally", "The imprinted Snurf-Snrpn chromosomal domain contains two large arrays of tandemly repeated, paternally expressed box C/D small-nucleolar RNA (snoRNA) genes: the SNORD115 (H/MBII-52) and SNORD116 (H/MBII-85) gene clusters believed to play key roles in the fine-tuning of serotonin receptor (5-HT2C) pre-mRNA processing and in the etiology of the Prader-Willi Syndrome (PWS), respectively.", "We demonstrate that the mouse C/D box snoRNA MBII-85 (SNORD116) is processed into at least five shorter RNAs using processing sites near known functional elements of C/D box snoRNAs.", "Although the SNORD116 gene cluster has become a prime candidate for PWS, it cannot be excluded that other paternally expressed genes in the chromosomal region 15q11q13 contribute to the full phenotype.", "In addition, recently published data provide strong evidence in support of a role for the snoRNA SNORD116 cluster (HBII-85) in PWS etiology", " Identification and characterization of this case provide unequivocal evidence for a critical role for the SNORD116 snoRNA molecules in PWS pathogenesis. ", "Our previous translocation studies predicted a major role for the C/D box small nucleolar RNA cluster SNORD116 (PWCR1/HBII-85) in PWS. ", "Snord116del mice with paternally derived deletion lack expression of this snoRNA. They have early-onset postnatal growth deficiency, but normal fertility and lifespan. While pituitary structure and somatotrophs are normal, liver Igf1 mRNA is decreased. In cognitive and behavior tests, Snord116del mice are deficient in motor learning and have increased anxiety. Around three months of age, they develop hyperphagia, but stay lean on regular and high-fat diet. On reduced caloric intake, Snord116del mice maintain their weight better than wild-type littermates, excluding increased energy requirement as a cause of hyperphagia. Normal compensatory feeding after fasting, and ability to maintain body temperature in the cold indicate normal energy homeostasis regulation. Metabolic chamber studies reveal that Snord116del mice maintain energy homeostasis by altered fuel usage. Prolonged mealtime and increased circulating ghrelin indicate a defect in meal termination mechanism. Snord116del mice, the first snoRNA deletion animal model, reveal a novel role for a non-coding RNA in growth and feeding regulation." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/24311433", "http://www.ncbi.nlm.nih.gov/pubmed/18320030", "http://www.ncbi.nlm.nih.gov/pubmed/22694955", "http://www.ncbi.nlm.nih.gov/pubmed/22495932", "http://www.ncbi.nlm.nih.gov/pubmed/21880592", "http://www.ncbi.nlm.nih.gov/pubmed/20803659", "http://www.ncbi.nlm.nih.gov/pubmed/22664655", "http://www.ncbi.nlm.nih.gov/pubmed/20588305" ]

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[ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012313", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D058727", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D020537" ]

[ "Drp1 is involved in the regulation of mitochondrial fission.", "Dynamin-related protein 1 (Drp1) mediates mitochondrial fission." ]

[ "mitochondrial fission" ]

[ "dynamin-related protein 1 (Drp1), a GTPase that mediates mitochondrial fission,", "dynamin-related protein 1 (DRP1), a protein required for mitochondrial network division.", "dynamin-related protein 1 (Drp1)-mediated mitochondrial fission", "Mitochondrial fission is mediated by dynamin-related protein 1 (Drp1),", "Drp1 is a dynamin-like GTPase that mediates mitochondrial and peroxisomal division in a process dependent on self-assembly and coupled to GTP hydrolysis. ", "Mitochondrial fission requires the dynamin GTPase Drp1, which assembles in a ring around the mitochondrion and appears to constrict both outer and inner mitochondrial membranes.", "DRP1; a mitochondrial fission protein", "Mitochondrial morphology is primarily controlled by the activation of dynamin-related proteins including dynamin-related protein 1 (Drp1), which promotes mitochondrial fission. ", "The change in mitochondrial morphology was caused by downregulation of the expression of Fis1 and Drp1, two proteins regulating mitochondrial fission.", "Furthermore, overexpression of the fission protein Drp1 (dynamin-related protein 1) or knocking down of the fusion protein OPA1 (optical atrophy 1) suppressed PINK1 RNAi-induced mitochondrial morphological defect, and overexpression of PINK1 or Parkin suppressed the elongated mitochondria phenotype caused by Drp1 RNAi.", "These results collectively indicate that ER-specific BNIP1 plays an important role in mitochondrial dynamics by modulating the mitochondrial fission protein Drp1 in a BH3 domain-dependent fashion.", "In the present study, we found a marked upregulation of mitochondrial fission protein dynamin-related protein 1 (Drp1) expression in human invasive breast carcinoma and metastases to lymph nodes.", "Mitochondrial remodeling was associated with increased proximity between Rab11a and mitochondrial membranes, changes in fusion-fission dynamics, and mitochondrial relocalization of the fission factor dynamin-related protein 1 (Drp1), which was regulated by the Rab11a effector protein FIP1/RCP.", "Functional analysis demonstrated that BNIP1 expression increased dynamin-related protein 1 (Drp1) expression followed by the mitochondrial translocation of Drp1 and subsequent mitochondrial fission.", "Role of dynamin-related protein 1 (Drp1)-mediated mitochondrial fission in oxygen sensing and constriction of the ductus arteriosus.", "In this study the role of the mitochondrial fission protein, Drp1 during Shigella infection in HeLa cells was examined", "In this study, we investigate the role of mitochondrial fission factor dynamin-related protein 1 (Drp1) in myogenic differentiation", "Role of dynamin-related protein 1 (Drp1)-mediated mitochondrial fission in oxygen sensing and constriction of the ductus arteriosus", "Functional analysis demonstrated that BNIP1 expression increased dynamin-related protein 1 (Drp1) expression followed by the mitochondrial translocation of Drp1 and subsequent mitochondrial fission", "These results collectively indicate that ER-specific BNIP1 plays an important role in mitochondrial dynamics by modulating the mitochondrial fission protein Drp1 in a BH3 domain-dependent fashion", "Glucocorticoid modulation of mitochondrial function in hepatoma cells requires the mitochondrial fission protein Drp1.", "Mitochondria in DRG neurons undergo hyperglycemic mediated injury through Bim, Bax and the fission protein Drp1.", "This novel function for DRP1 is distinct from its recognized role in regulating mitochondrial fission. ", "Abnormal interaction between the mitochondrial fission protein Drp1 and hyperphosphorylated tau in Alzheimer's disease neurons: implications for mitochondrial dysfunction and neuronal damage.", "SUMOylation of the mitochondrial fission protein Drp1 occurs at multiple nonconsensus sites within the B domain and is linked to its activity cycle.", "Dynamic regulation of mitochondrial fission through modification of the dynamin-related protein Drp1.", "We highlight posttranslational modifications of the mitochondrial fission protein Drp1, for which these regulatory mechanisms are best characterized.", "Furthermore, overexpression of the fission protein Drp1 (dynamin-related protein 1) or knocking down of the fusion protein OPA1 (optical atrophy 1) suppressed PINK1 RNAi-induced mitochondrial morphological defect, and overexpression of PINK1 or Parkin suppressed the elongated mitochondria phenotype caused by Drp1 RNAi. Functionally, PINK1 knockdown and overexpression had opposite effects on dendritic spine formation and neuronal vulnerability to excitotoxicity.", "In this study the role of the mitochondrial fission protein, Drp1 during Shigella infection in HeLa cells was examined." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/24302731", "http://www.ncbi.nlm.nih.gov/pubmed/17015472", "http://www.ncbi.nlm.nih.gov/pubmed/23027751", "http://www.ncbi.nlm.nih.gov/pubmed/22334657", "http://www.ncbi.nlm.nih.gov/pubmed/23888838", "http://www.ncbi.nlm.nih.gov/pubmed/23904108", "http://www.ncbi.nlm.nih.gov/pubmed/20850011", "http://www.ncbi.nlm.nih.gov/pubmed/25658204", "http://www.ncbi.nlm.nih.gov/pubmed/23334860", "http://www.ncbi.nlm.nih.gov/pubmed/16684605", "http://www.ncbi.nlm.nih.gov/pubmed/25012575", "http://www.ncbi.nlm.nih.gov/pubmed/22703557", "http://www.ncbi.nlm.nih.gov/pubmed/24080278", "http://www.ncbi.nlm.nih.gov/pubmed/19638400", "http://www.ncbi.nlm.nih.gov/pubmed/23128392", "http://www.ncbi.nlm.nih.gov/pubmed/24485837", "http://www.ncbi.nlm.nih.gov/pubmed/25036098", "http://www.ncbi.nlm.nih.gov/pubmed/24388463", "http://www.ncbi.nlm.nih.gov/pubmed/20649536", "http://www.ncbi.nlm.nih.gov/pubmed/22020994", "http://www.ncbi.nlm.nih.gov/pubmed/25348719", "http://www.ncbi.nlm.nih.gov/pubmed/24878071", "http://www.ncbi.nlm.nih.gov/pubmed/20179104", "http://www.ncbi.nlm.nih.gov/pubmed/15791210", "http://www.ncbi.nlm.nih.gov/pubmed/25192600", "http://www.ncbi.nlm.nih.gov/pubmed/24764190", "http://www.ncbi.nlm.nih.gov/pubmed/22367970", "http://www.ncbi.nlm.nih.gov/pubmed/24755420", "http://www.ncbi.nlm.nih.gov/pubmed/24631294", "http://www.ncbi.nlm.nih.gov/pubmed/24616159", "http://www.ncbi.nlm.nih.gov/pubmed/21613270", "http://www.ncbi.nlm.nih.gov/pubmed/21459773", "http://www.ncbi.nlm.nih.gov/pubmed/25237193", "http://www.ncbi.nlm.nih.gov/pubmed/26038571", "http://www.ncbi.nlm.nih.gov/pubmed/25332205" ]

[ { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A0112997", "o": "D012380" } ]

[ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D024101", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012380" ]

[ "Fanconi anemia complementation group D1 (FANCD1) was shown to be induced by biallelic mutations in the BRCA2 breast-cancer-susceptibility gene." ]

[]

[ "The discovery of biallelic BRCA2 mutations in the FA-D1 complementation group allows for the first time to study the characteristics of primary BRCA2-deficient human cells.", "Although he lacked a strong family history of cancer, he was subsequently shown to carry biallelic mutations in the FANCD1/BRCA2 gene. These included an IVS7 splice-site mutation, which is strongly associated with early AML in homozygous or compound heterozygous carrier status in FA-D1 patients.", "Biallelic BRCA2 mutations were shown recently to cause FA-D1. ", "The breast cancer susceptibility gene BRCA2 was recently found to be associated with Fanconi anemia complementation group D1 (FA-D1)", "One kindred, of Ashkenazi Jewish ancestry, had five members who were diagnosed with breast cancer and two cousins who were BRCA2*6174delT/C3069X compound heterozygotes and had Fanconi anemia and brain tumors", "In another kindred of Ashkenazi Jewish and Lithuanian Catholic ancestry, a child with Fanconi anemia and a medulloblastoma was a BRCA2*6174delT/886delGT compound heterozygote", "Two other kindreds each contained a Fanconi anemia-afflicted child who developed medulloblastoma; one child was of Latin American ancestry and a compound heterozygote for BRCA2*I2490T/ 5301insA and the other was African American and a compound heterozygote for BRCA2*Q3066X/E1308X", "Surprisingly, biallelic mutations in the BRCA2 breast-cancer-susceptibility gene were found in Fanconi anemia (FA), a rare hereditary disorder characterized by chromosomal instability, hypersensitivity to DNA cross-linking agents, and cancer susceptibility", " The breast cancer susceptibility gene BRCA2 was recently found to be associated with Fanconi anemia complementation group D1 (FA-D1).", "Biallelic mutations in Fanconi anemia complementation group genes disrupt DNA repair and result in the complex Fanconi anemia phenotype.", "Thirteen complementation groups and genes are identified, including BRCA2, which is defective in the FA-D1 group.", "Biallelic BRCA2 mutations were shown recently to cause FA-D1.", "Biallelic BRCA2 mutations were shown recently to cause FA-D1", "Thirteen complementation groups and genes are identified, including BRCA2, which is defective in the FA-D1 group" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/15695377", "http://www.ncbi.nlm.nih.gov/pubmed/15645491", "http://www.ncbi.nlm.nih.gov/pubmed/18212739", "http://www.ncbi.nlm.nih.gov/pubmed/14559878", "http://www.ncbi.nlm.nih.gov/pubmed/14695169", "http://www.ncbi.nlm.nih.gov/pubmed/12383764", "http://www.ncbi.nlm.nih.gov/pubmed/16920162" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D051856", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D024682", "http://www.uniprot.org/uniprot/BRCA2_MOUSE" ]