Datasets:

HiTZ

/

Multilingual-BioASQ-6B

like 2

Follow

HiTZ zentroa 55

[ "Cyclophilins are ubiquitously expressed proteins that bind to prolines." ]

[ "yes" ]

[ "Cyclophilins are ubiquitously expressed proteins that bind to prolines and can catalyse cis/trans isomerization of proline residues.", "a characteristic of the cyclophilin family of proteins that bind prolines and often act as cis-trans peptidyl-prolyl isomerases. ", "The cyclophilins are widely expressed enzymes that catalyze the interconversion of the cis and trans peptide bonds of prolines. ", " an immunophilin on the isomerization of critical prolines that are found in the tCHT1 sequence." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/24831536", "http://www.ncbi.nlm.nih.gov/pubmed/12358793", "http://www.ncbi.nlm.nih.gov/pubmed/25967372", "http://www.ncbi.nlm.nih.gov/pubmed/18823995" ]

[]

[]

[ "A given genotype can be either beneficial or detrimental, even deleterious, depending on the environment in which an organism lives. This is known as antagonistic pleiotropy. Antagonistic pleiotropy can operate even within the same environment. For example, in Escherichia coli, certain mutations can exhibit beneficial, deleterious or neutral fitness effects at different growth rates. Also, antagonistic pleiotropy is involved in the evolution of ageing, since a certain genotype may affect late- and early-life fitness in opposite directions." ]

[ "yes" ]

[ "Mutations beneficial in one environment may cause costs in different environments, resulting in antagonistic pleiotropy. Here, we describe a novel form of antagonistic pleiotropy that operates even within the same environment, where benefits and deleterious effects exhibit themselves at different growth rates.", "The hfq mutations were beneficial, deleterious or neutral at an intermediate growth rate (0.5 h(-1)) and one changed from beneficial to deleterious within a 36 min difference in doubling time.", "Two genetic models exist to explain the evolution of ageing - mutation accumulation (MA) and antagonistic pleiotropy (AP).", "Under AP, late-acting deleterious mutations accumulate because they confer beneficial effects early in life.", "Many marker loci responded in opposite directions to selection for late- and early-life fitness, indicating negative genetic correlations or trade-offs between those traits. Indirect evidence suggested that some negative genetic correlations were due to antagonistic pleiotropy.", "Here, we describe a novel form of antagonistic pleiotropy that operates even within the same environment, where benefits and deleterious effects exhibit themselves at different growth rates.", "The basis of antagonistic pleiotropy in hfq mutations that have opposite effects on fitness at slow and fast growth rates.", "Here, we describe a novel form of antagonistic pleiotropy that operates even within the same environment, where benefits and deleterious effects exhibit themselves at different growth rates" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/23169561", "http://www.ncbi.nlm.nih.gov/pubmed/15454545", "http://www.ncbi.nlm.nih.gov/pubmed/19226414" ]

[]

[]

[ "Yes, the protein SETMAR (Metnase) has a transposase domain." ]

[ "yes" ]

[ "Metnase (SETMAR) is a SET-transposase fusion protein that promotes nonhomologous end joining (NHEJ) repair in humans.", "The transposase domain protein Metnase/SETMAR suppresses chromosomal translocations.", " Metnase (also termed SETMAR) is a fusion of a histone methylase and transposase protein that arose specifically in primates. ", "the only intact Hsmar1 transposase gene exists within a chimeric SET-transposase fusion protein referred to as Metnase or SETMAR. ", "The Metnase transposase has been remarkably conserved through evolution;", "Metnase (also known as SETMAR) is a SET and transposase fusion protein in humans and plays a positive role in double-strand break (DSB) repair. While the SET domain possesses histone lysine methyltransferase activity, the transposase domain is responsible for 5'-terminal inverted repeat (TIR)-specific binding, DNA looping, and DNA cleavage activities. ", "Metnase is a fusion gene comprising a SET histone methyl transferase domain and a transposase domain derived from the Mariner transposase.", "ulated by the DNA repair component Metnase (also termed SETMAR). Metnase contains a SET histone methylase and transposase nuclease domain", "Metnase is a human SET and transposase domain protein ", "The human set and transposase domain protein Metnase", " of transposase-related sequences in humans are pseudogenes. We recently isolated and characterized a SET and transposase domain protein termed Metnase that promotes DNA double-strand break (DSB) repair by non-homologous end-joining (NHEJ). Both the SET and transposase domain were required for its NHEJ activity.", "Metnase, also known as SETMAR, is a SET and transposase fusion protein with an undefined role in mammalian DNA repair.", "Biochemical characterization of a SET and transposase fusion protein, Metnase: i", "Metnase (SETMAR) is a SET and transposase fusion protein that promotes in vivo end joining activity and mediates genomic integration of foreign DNA. ", " This transposase coding region is part of the SETMAR gene, in which a histone methylatransferase SET domain is fused to an Hsmar1 transposase domain. ", "The human SETMAR protein preserves most of the activities of the ancestral Hsmar1 transposase.", "ere we investigate the activity of the human SETMAR protein, a highly expressed fusion between a histone H3 methylase and a mariner family transposase.", "SETMAR, a new primate chimeric gene resulting from fusion of a SET histone methyltransferase gene to the transposase gene of a mobile element.", "We identified a protein, termed Metnase, that has a SET domain and a transposase/nuclease domain. ", "Metnase has a nuclease domain that shares homology with the Transposase family.", "Metnase (also called SETMAR) is a SET and transposase domain protein that promotes both DNA double-strand break (DSB) repair and restart of stalled replication forks. " ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/18790802", "http://www.ncbi.nlm.nih.gov/pubmed/22231448", "http://www.ncbi.nlm.nih.gov/pubmed/20620605", "http://www.ncbi.nlm.nih.gov/pubmed/20309721", "http://www.ncbi.nlm.nih.gov/pubmed/17877369", "http://www.ncbi.nlm.nih.gov/pubmed/21491884", "http://www.ncbi.nlm.nih.gov/pubmed/17130240", "http://www.ncbi.nlm.nih.gov/pubmed/16332963", "http://www.ncbi.nlm.nih.gov/pubmed/18263876", "http://www.ncbi.nlm.nih.gov/pubmed/17403897", "http://www.ncbi.nlm.nih.gov/pubmed/23090115", "http://www.ncbi.nlm.nih.gov/pubmed/18773976", "http://www.ncbi.nlm.nih.gov/pubmed/20416268", "http://www.ncbi.nlm.nih.gov/pubmed/20521842", "http://www.ncbi.nlm.nih.gov/pubmed/16672366", "http://www.ncbi.nlm.nih.gov/pubmed/19458360" ]

[]

[ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0004803", "http://www.uniprot.org/uniprot/SETMR_HUMAN", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D019895", "http://www.uniprot.org/uniprot/SETMR_RAT", "http://www.uniprot.org/uniprot/TRAT_CHEHE", "http://www.uniprot.org/uniprot/TRA_BPMU", "http://www.uniprot.org/uniprot/SETMR_MOUSE", "http://www.uniprot.org/uniprot/SETMR_BOVIN" ]

[ "Yes, alternative splicing seem to play a key role in the response to DNA or mitocondrial damage as suggested by the number of apoptotic genes that are alternatively spliced, with often antagonistic roles of the isoforms generated." ]

[ "yes" ]

[ "Apoptosis promoted by UV in cells lacking p53 is prevented when the change in AS of the apoptotic gene bcl-x is reverted, confirming the relevance of this mechanism.", "We demonstrate that E2F1 requires SC35 to switch the alternative splicing profile of various apoptotic genes such as c-flip, caspases-8 and -9 and Bcl-x, towards the expression of pro-apoptotic splice variants. Finally, we provide evidence that E2F1 upregulates SC35 in response to DNA-damaging agents and show that SC35 is required for apoptosis in response to these drugs.", "This analysis revealed that DNA damage resulted in changes in splicing activity that modified the splicing pattern of Fas, a key pro-apoptotic, p53-inducible death receptor.", "Bortezomib induces mitochondrial damage in native cells and also activates the UPR by splicing of Xbp-1 and induction of CHOP, which is significantly reduced by silencing of MUC4.", "The tumour-suppressor protein p53 is an important activator of apoptosis. Although p53-deficient cancer cells are less responsive to chemotherapy, their resistance is not complete, which suggests that other apoptotic pathways may exist. A p53-related gene, p73, which encodes several proteins as a result of alternative splicing, can also induce apoptosis.", "Induction of apoptosis was significantly reduced in P388/SPR cells, as indicated by minimal DNA fragmentation. Analysis of oncogenes regulating apoptotic cell death revealed a marked decrease of bcl-2 in combination with a moderate reduction of bax protein, but a striking overexpression of the long form of the bcl-X protein." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/19450518", "http://www.ncbi.nlm.nih.gov/pubmed/18806759", "http://www.ncbi.nlm.nih.gov/pubmed/9010037", "http://www.ncbi.nlm.nih.gov/pubmed/17692132", "http://www.ncbi.nlm.nih.gov/pubmed/19690168", "http://www.ncbi.nlm.nih.gov/pubmed/21483803", "http://www.ncbi.nlm.nih.gov/pubmed/19170108", "http://www.ncbi.nlm.nih.gov/pubmed/18571879", "http://www.ncbi.nlm.nih.gov/pubmed/18211505", "http://www.ncbi.nlm.nih.gov/pubmed/12067235", "http://www.ncbi.nlm.nih.gov/pubmed/10391249", "http://www.ncbi.nlm.nih.gov/pubmed/22266985" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004249", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D017398" ]

[ "Cellular senescence can be induced through activation or inactivation of a number of oncogenes, such as Ras, c-Abl, Raf, Myc, Skp2, BRAF, AKT, HDAC2, p38 MAPK, Caveolin-1 and Mek1." ]

[ "Ras", "c-Abl", "Raf", "Myc", "Skp2", "BRAF", "AKT", "HDAC2", "p38 MAPK", "Caveolin-1", "Mek1" ]

[ "ROS-generating oxidases Nox1 and Nox4 contribute to oncogenic Ras-induced premature senescence", "Activated oncogenes induce premature cellular senescence, a permanent state of proliferative arrest in primary rodent and human fibroblasts. Recent studies suggest that generation of reactive oxygen species (ROS) is involved in oncogenic Ras-induced premature senescence.", "these findings suggest that Nox1- and Nox4-generated ROS play an important role in Ras-induced premature senescence", "A role for c-Abl in cell senescence and spontaneous immortalization", "Here, we report an important role for c-Abl in replicative senescence and immortalization by regulating the expression of two tumor suppressors that induce cellular senescence, p53 and p16(INK4a).", "The role for c-Abl in regulating cell senescence and immortalization might explain some of the developmental defects in c-Abl (-/-) mice and how BCR-ABL transforms cells.", "Ras/Raf-prototypic oncogenes induce cellular senescence, a terminal cell-cycle arrest, as a default cellular safeguard program", "oncogene-induced senescence, Myc style", "We review and discuss here evidence for Myc-induced senescence - which is detectable to a limited degree as a cell-autonomous, direct response to Myc action, but occurs predominantly in a non-cell-autonomous fashion via crosstalk of the oncogene-driven cell population with non-neoplastic bystanders, namely cells of the host immune system, prompting them to release pro-senescent cytokines that strike back onto adjacent proliferating tumor cells.", "genetic Skp2 inactivation evokes cellular senescence even in oncogenic conditions in which the p19(Arf)-p53 response is impaired, whereas a Skp2-SCF complex inhibitor can trigger cellular senescence in p53/Pten-deficient cells and tumour regression in preclinical studies.", "Activated RAS/BRAF oncogenes induce cellular senescence as a tumor-suppressive barrier in early cancer development, at least in part, via an oncogene-evoked DNA damage response (DDR).", "Cdk2 suppresses cellular senescence induced by the c-myc oncogene", "Loss of Cdk2 also caused sensitization to Myc-induced senescence in pancreatic beta-cells or splenic B-cells in vivo", "Myc also causes senescence in cells lacking the DNA repair protein Wrn.", "In MEFs, Myc-induced senescence was genetically dependent on the ARF-p53-p21Cip1 and p16INK4a-pRb pathways, p21Cip1 and p16INK4a being selectively induced in Cdk2-/- cells.", "We have found that expression of such an oncogene, Akt, causes senescence in primary mouse hepatoblasts in vitro.", "hyperproliferative signaling through AKT might be a driving force of the senescence in activated hepatic stellate cells.", "oncogenic RAS expression, which causes genotoxic stress and senescence in normal cells,", "Here we report that the suppression of the c-Myc (MYC) oncogene induces cellular senescence in diverse tumor types including lymphoma, osteosarcoma, and hepatocellular carcinoma.", "Cellular senescence is an important mechanism of tumor regression upon c-Myc inactivation", "MYC inactivation was associated with prototypical markers of senescence", "only after lymphomas were repaired for p53 expression did MYC inactivation induce robust senescence and sustained tumor regression.", "Replicative senescence due to telomere shortening can, for example, be induced by a dominant negative version of telomerase, premature senescence by the overexpression of oncogenic ras, or p16.", "knockdown of HDAC2 induced cellular senescence.", "MYC overexpression is thought to initiate tumorigenesis by inducing cellular proliferation and growth and to be restrained from causing tumorigenesis by inducing cell cycle arrest, cellular senescence, and/or apoptosis.", "Several conditions, including oncogenic Ras over-expression and inappropriate culture conditions, also induce senescence without telomere shortening.", "We demonstrate that p38 mitogen-activated protein kinase (MAPK) plays important causative roles in senescent cells following telomere shortening, Ras-Raf activation, oxidative stress or inappropriate culture conditions.", "Mitogen-activated protein kinase p38 defines the common senescence-signalling pathway", "These results indicate that p38 comprises the senescence-executing pathway in response to diverse stimuli.", "this p38-activating condition appears to be defined quantitatively as a sum of continuous and low-level stresses, and remains even after the initial stimuli are withdrawn, which may explain the well-known irreversible nature of cellular senescence. We also show that papilloma virus E7 abolishes the p38-induced growth arrest but not other senescence-associated phenotypes, indicating the differential role of pRb in the downstream of p38.", "Expression of caveolin-1 induces premature cellular senescence in primary cultures of murine fibroblasts", "Here, we demonstrate that mouse embryonic fibroblasts transgenically overexpressing caveolin-1 show: 1) a reduced proliferative lifespan; 2) senescence-like cell morphology; and 3) a senescence-associated increase in beta-galactosidase activity. These results indicate for the first time that the expression of caveolin-1 in vivo is sufficient to promote and maintain the senescent phenotype.", "Interestingly, premature senescence induced by hydrogen peroxide is greatly reduced in NIH 3T3 cells harboring antisense caveolin-1. Importantly, induction of premature senescence is recovered when caveolin-1 levels are restored.", "these results clearly indicate a central role for caveolin-1 in promoting cellular senescence", "Oncogenic activation of the mitogen-activated protein (MAP) kinase cascade in murine fibroblasts initiates a senescence-like cell cycle arrest that depends on the ARF/p53 tumor suppressor pathway.", "In contrast, coexpression of oncogenic ras or activated mek1 with p53 enhanced both p53 levels and activity relative to that observed for p53 alone and produced an irreversible cell cycle arrest that displayed features of cellular senescence.", "our results indicate that oncogenic activation of the MAP kinase pathway in murine fibroblasts converts p53 into a senescence inducer through both quantitative and qualitative mechanisms.", "Myc-evoked apoptosis serves as a signal for macrophage attraction and activation, followed by the secretion of TGF-β as a cytokine that is capable of terminally arresting Myc-driven lymphoma cells without causing further DNA damage and without launching a senescence-associated, pro-inflammatory, and, therefore, potentially detrimental cytokine response in the target population.", "The suppression of oncogenic levels of MYC is sufficient to induce sustained tumor regression associated with proliferative arrest, differentiation, cellular senescence, and/or apoptosis, a phenomenon known as oncogene addiction." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/23216904", "http://www.ncbi.nlm.nih.gov/pubmed/19053174", "http://www.ncbi.nlm.nih.gov/pubmed/20010815", "http://www.ncbi.nlm.nih.gov/pubmed/17409421", "http://www.ncbi.nlm.nih.gov/pubmed/17634581", "http://www.ncbi.nlm.nih.gov/pubmed/11971980", "http://www.ncbi.nlm.nih.gov/pubmed/22791394", "http://www.ncbi.nlm.nih.gov/pubmed/22019769", "http://www.ncbi.nlm.nih.gov/pubmed/17664422", "http://www.ncbi.nlm.nih.gov/pubmed/20227040", "http://www.ncbi.nlm.nih.gov/pubmed/16818632", "http://www.ncbi.nlm.nih.gov/pubmed/20237562", "http://www.ncbi.nlm.nih.gov/pubmed/12581156", "http://www.ncbi.nlm.nih.gov/pubmed/21969595", "http://www.ncbi.nlm.nih.gov/pubmed/12134086", "http://www.ncbi.nlm.nih.gov/pubmed/19150958" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016922", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:2000773", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:2000772", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:2000774", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016283", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0090398", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011905", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D018631", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016315", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016313", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016374", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0090402" ]

[ "HbVar (http://globin.cse.psu.edu) is a relational database of hemoglobin variants and thalassemia mutations. Extensive information is recorded for each variant and mutation, including a description of the variant and associated pathology, hematology, electrophoretic mobility, methods of isolation, stability information, ethnic occurrence, structure studies, functional studies, and references. The initial information was derived from books by Dr. Titus Huisman and colleagues [Huisman et al., 1996, 1997, 1998]. The current database is updated regularly with the addition of new data and corrections to previous data. Queries can be formulated based on fields in the database. Tables of common categories of variants, such as all those involving the alpha1-globin gene (HBA1) or all those that result in high oxygen affinity, are maintained by automated queries on the database. Users can formulate more precise queries, such as identifying \"all beta-globin variants associated with instability and found in Scottish populations.\" This new database should be useful for clinical diagnosis as well as in fundamental studies of hemoglobin biochemistry, globin gene regulation, and human sequence variation at these loci." ]

[]

[ "HbVar: A relational database of human hemoglobin variants and thalassemia mutations at the globin gene server.", "We have constructed a relational database of hemoglobin variants and thalassemia mutations, called HbVar, which can be accessed on the web at http://globin.cse.psu.edu. Extensive information is recorded for each variant and mutation, including a description of the variant and associated pathology, hematology, electrophoretic mobility, methods of isolation, stability information, ethnic occurrence, structure studies, functional studies, and references. The initial information was derived from books by Dr. Titus Huisman and colleagues [Huisman et al., 1996, 1997, 1998]. The current database is updated regularly with the addition of new data and corrections to previous data. Queries can be formulated based on fields in the database. Tables of common categories of variants, such as all those involving the alpha1-globin gene (HBA1) or all those that result in high oxygen affinity, are maintained by automated queries on the database. Users can formulate more precise queries, such as identifying \"all beta-globin variants associated with instability and found in Scottish populations.\" This new database should be useful for clinical diagnosis as well as in fundamental studies of hemoglobin biochemistry, globin gene regulation, and human sequence variation at these loci.", "A registry of these Hb variants and other information, a legacy from Professor Huisman, is now available online, at HbVar database (hhtp://globin.bx.psu.edu/hbvar).", "HbVar (http://globin.bx.psu.edu/hbvar) is a locus-specific database (LSDB) developed in 2001 by a multi-center academic effort to provide timely information on the genomic sequence changes leading to hemoglobin variants and all types of thalassemia and hemoglobinopathies.", "HbVar (http://globin.cse.psu.edu/globin/hbvar/) is a relational database developed by a multi-center academic effort to provide up-to-date and high quality information on the genomic sequence changes leading to hemoglobin variants and all types of thalassemia and hemoglobinopathies.", "HbVar (http://globin.bx.psu.edu/hbvar) is one of the oldest and most appreciated locus-specific databases launched in 2001 by a multi-center academic effort to provide timely information on the genomic alterations leading to hemoglobin variants and all types of thalassemia and hemoglobinopathies.", "HbVar database of human hemoglobin variants and thalassemia mutations: 2007 update.", "Updates of the HbVar database of human hemoglobin variants and thalassemia mutations.", "Improvements in the HbVar database of human hemoglobin variants and thalassemia mutations for population and sequence variation studies.", "HbVar (http://globin.bx.psu.edu/hbvar) is one of the oldest and most appreciated locus-specific databases launched in 2001 by a multi-center academic effort to provide timely information on the genomic alterations leading to hemoglobin variants and all types of thalassemia and hemoglobinopathies. ", "We have constructed a relational database of hemoglobin variants and thalassemia mutations, called HbVar, which can be accessed on the web at http://globin.cse.psu.edu. ", "We have constructed a relational database of hemoglobin variants and thalassemia mutations, called HbVar, which can be accessed on the web at http://globin.cse.psu.edu.", "HbVar (http://globin.bx.psu.edu/hbvar) is a locus-specific database (LSDB) developed in 2001 by a multi-center academic effort to provide timely information on the genomic sequence changes leading to hemoglobin variants and all types of thalassemia and hemoglobinopathies.", "HbVar (http://globin.cse.psu.edu/globin/hbvar/) is a relational database developed by a multi-center academic effort to provide up-to-date and high quality information on the genomic sequence changes leading to hemoglobin variants and all types of thalassemia and hemoglobinopathies.", "HbVar (http://globin.bx.psu.edu/hbvar) is one of the oldest and most appreciated locus-specific databases launched in 2001 by a multi-center academic effort to provide timely information on the genomic alterations leading to hemoglobin variants and all types of thalassemia and hemoglobinopathies.", "A registry of these Hb variants and other information, a legacy from Professor Huisman, is now available online, at HbVar database (hhtp://globin.bx.psu.edu/hbvar)." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/17221864", "http://www.ncbi.nlm.nih.gov/pubmed/14681476", "http://www.ncbi.nlm.nih.gov/pubmed/21932936", "http://www.ncbi.nlm.nih.gov/pubmed/11857738", "http://www.ncbi.nlm.nih.gov/pubmed/24137000" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D017085", "http://www.disease-ontology.org/api/metadata/DOID:10241", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D017086", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D019991", "http://www.biosemantics.org/jochem#4249395", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005319", "http://www.disease-ontology.org/api/metadata/DOID:1099", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D006441", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D055538", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013789" ]

[ "Quantitative precisions improved significantly when DMSO (dimethylsulfoxide) was added to the matrix solution.\nIntroducing to the 80% formic acid injection solution an organic solvent such as acetonitrile or acetonitrile-DMSO induced further retention selectivity, and increasing levels of organic solvents reduced on-column retention.\nLow percentages of dimethylsulfoxide (DMSO) in liquid chromatography solvents lead to a strong enhancement of electrospray ionization of peptides, improving the sensitivity of protein identification in bottom-up proteomics by up to tenfold.", "Llow percentages of dimethylsulfoxide (DMSO) in liquid chromatography solvents lead to a strong enhancement of electrospray ionization of peptides, improving the sensitivity of protein identification in bottom-up proteomics by up to tenfold. Additionally, the presence of DMSO in the sample allow the retention time selectivity of the peptides." ]

[]

[ "Introducing to the 80% formic acid injection solution an organic solvent such as acetonitrile or acetonitrile-DMSO induced further retention selectivity, and increasing levels of organic solvents reduced on-column retention.", "We report that low percentages of dimethylsulfoxide (DMSO) in liquid chromatography solvents lead to a strong enhancement of electrospray ionization of peptides, improving the sensitivity of protein identification in bottom-up proteomics by up to tenfold. ", "We found that the quantitative precisions improved significantly when DMSO (dimethylsulfoxide) was added to the matrix solution." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/18393531", "http://www.ncbi.nlm.nih.gov/pubmed/18926777", "http://www.ncbi.nlm.nih.gov/pubmed/23975139" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D020543", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D040901", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004121", "http://www.biosemantics.org/jochem#4275915" ]

[ "Modulation of the immune system by targeting coinhibitory and costimulatory receptors has become a promising new approach of immunotherapy for cancer. OBJECTIVE: CT-011 is a humanized IgG1 monoclonal antibody that modulates the immune response through interaction with PD-1, a protein belonging to the B7 receptor family present on lymphocytes. The objectives of this phase I study were to assess the dose-limiting toxicities, to determine the maximum tolerated dose, and to study the pharmacokinetics of CT-011 administered once to patients with advanced hematologic malignancies. We have developed a cancer vaccine in which autologous tumor is fused with dendritic cells resulting in the presentation of tumor antigens in the context of DC-mediated costimulation. The median t1/2 of CT-011 ranged from 217 to 410 hours. The PD1/PDL1 pathway is an important element contributing to tumor-mediated immune suppression. The recent approval of the CTLA-4-blocking antibody ipilimumab for the treatment of melanoma was a watershed event, opening up a new era in the field of immunotherapy. T-cell expression of programmed death receptor-1 down-regulates the immune response against malignancy by interacting with cognate ligands ( eg, PD-L1 ) on tumor cells; however, little is known regarding PD-1 and natural killer ( NK ) cells. ", "PD-1" ]

[ "PD-1" ]

[ "we find that using an anti-PD-1 antibody (CT-011)", "PD-1 blockade by CT-011, anti-PD-1 antibody,", ". Presence of CT-011, an anti-PD1 antibody,", "CT-011, a novel monoclonal anti-PD-1 antibody", "CT-011, a humanized antibody interacting with PD-1,", "Anti-PD1 (nivolumab and MK-3475)", "anti-PD-1 antibodies MK-3475" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/23460532", "http://www.ncbi.nlm.nih.gov/pubmed/20460501", "http://www.ncbi.nlm.nih.gov/pubmed/21577144", "http://www.ncbi.nlm.nih.gov/pubmed/23263823", "http://www.ncbi.nlm.nih.gov/pubmed/21710477", "http://www.ncbi.nlm.nih.gov/pubmed/18483370" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D000918", "http://www.disease-ontology.org/api/metadata/DOID:1909", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D008545", "http://www.disease-ontology.org/api/metadata/DOID:4159", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D058950" ]

[ "Alternative splicing of the locus AbetaH-J-J (asparetyl-beta-hydroxylase) generates three functionally distinct proteins: an enzyme, AbetaH (aspartyl-beta-hydroxylase), a structural protein of the sarcoplasmic reticulum membrane (junctin), and an integral membrane calcium binding protein (junctate). Aspartyl (asparaginyl)-beta-hydroxylase (AAH), has also two related transcripts, Humbug and Junctin, which lack catalytic domains. The smallest BAH-related transcript (2,789 base pairs) uses an alternative 3' terminal exon, resulting in a protein lacking a catalytic domain. Evolutionary conservation of this noncatalytic isoform of BAH (humbug) is demonstrated in mouse, man, and Drosophila. A human junctin isoform (isoform 1, 225 aa) was also identified and characterized. The isoform 1 has a 15 aa insertion at the amino acid residue 55 of the human junctin." ]

[ "Aspartyl-beta-hydroxylase", "Aspartyl (asparaginyl)-beta-hydroxylase", "AbetaH", "AAH", "BAH", "humbug", "junctate", "junctin", "junctin isoform" ]

[ "The single genomic locus, AbetaH-J-J, encodes three functionally distinct proteins aspartyl beta-hydroxylase, junctin and junctate by alternative splicing.", "The human AbetaH-J-J locus is a genomic sequence which generates three functionally distinct proteins, the enzyme aspartyl-beta-hydroxylase (AbetaH), the structural protein of sarcoplasmic reticulum junctin, and the membrane-bound calcium binding protein junctate.", "Aspartyl (asparaginyl)-beta-hydroxylase (AAH) hydroxylates Asp and Asn residues within EGF-like domains of Notch and Jagged, which mediate cell motility and differentiation. This study examines the expression, regulation and function of AAH, and its related transcripts, Humbug and Junctin, which lack catalytic domains, using SH-Sy5y neuroblastoma cells.", "Alternative splicing of the locus AbetaH-J-J generates three functionally distinct proteins: an enzyme, AbetaH (aspartyl-beta-hydroxylase), a structural protein of the sarcoplasmic reticulum membrane (junctin), and an integral membrane calcium binding protein (junctate).", "Junctate is a newly identified integral ER/SR membrane calcium binding protein, which is an alternative splicing form of the same gene generating aspartyl beta-hydroxylase and junctin.", "Screening a mouse heart cDNA library using canine junctin cDNA as a probe yielded three complete mouse heart cDNAs. One of the cDNAs is homologous to the previously reported human junctate.", "Screening a cDNA library from human skeletal muscle and cardiac muscle with a cDNA probe derived from junctin led to the isolation of two groups of cDNA clones. The first group displayed a deduced amino acid sequence that is 84% identical to that of dog heart junctin, whereas the second group had a single open reading frame that encoded a polypeptide with a predicted mass of 33 kDa, whose first 78 NH(2)-terminal residues are identical to junctin whereas its COOH terminus domain is identical to aspartyl beta-hydroxylase, a member of the alpha-ketoglutarate-dependent dioxygenase family. We named the latter amino acid sequence junctate.", "Our study shows that alternative splicing of the same gene generates the following functionally distinct proteins: an enzyme (aspartyl beta-hydroxylase), a structural protein of SR (junctin), and a membrane-bound calcium binding protein (junctate).", "Junctin is a calsequestrin binding protein detected in junctional sarcoplasmic reticulum of striated muscles. In the present study, the human cardiac junctin cDNA has been cloned by human heart cDNA library screening and RT-PCR, and the cDNA sequence has been determined. The deduced amino acid sequence of human junctin (210 aa) has 84% sequence identity to that of canine junctin identified previously. A human junctin isoform (isoform 1, 225 aa) was also identified and characterized. The isoform 1 has a 15 aa insertion at the amino acid residue 55 of the human junctin. Northern blot analysis revealed that the human junctin was present both in cardiac and skeletal muscles, and the sizes of the transcripts were approximately 3.0 and 4.2kb. Amino acid residues 6-78 of human junctin and 35-107 of human aspartyl beta-hydroxylase (hAspH) overlapped perfectly.", "The mouse aspartyl beta-hydroxylase gene (Asph, BAH) has been cloned and characterized. The mouse BAH gene spans 200 kilobase pairs of genomic DNA and contains 24 exons. Of three major BAH-related transcripts, the two largest (6,629 and 4,419 base pairs) encode full-length protein and differ only in the use of alternative polyadenylation signals. The smallest BAH-related transcript (2,789 base pairs) uses an alternative 3' terminal exon, resulting in a protein lacking a catalytic domain. Evolutionary conservation of this noncatalytic isoform of BAH (humbug) is demonstrated in mouse, man, and Drosophila.", "The single genomic locus, AbetaH-J-J, encodes three functionally distinct proteins aspartyl beta-hydroxylase, junctin and junctate by alternative splicing", "Multiple levels of control of the expression of the human A beta H-J-J locus encoding aspartyl-beta-hydroxylase, junctin, and junctate.", "A human junctin isoform (isoform 1, 225 aa) was also identified and characterized" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/17706594", "http://www.ncbi.nlm.nih.gov/pubmed/17341613", "http://www.ncbi.nlm.nih.gov/pubmed/11007777", "http://www.ncbi.nlm.nih.gov/pubmed/10974562", "http://www.ncbi.nlm.nih.gov/pubmed/17156427", "http://www.ncbi.nlm.nih.gov/pubmed/10956665", "http://www.ncbi.nlm.nih.gov/pubmed/11735129", "http://www.ncbi.nlm.nih.gov/pubmed/15798210" ]

[]

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

[ "Yes-associated protein (YAP), a transcription coactivator, is the major downstream effector of the Hippo pathway, which plays a critical role in organ size control, cell poliferation and cancer development and tissue homeostasis and differentiation." ]

[ "cell proliferation", "organ size control", "cancer development", "tissue homeostasis", "cell differentiation" ]

[ "in which YAP appears to regulate cell proliferation ", "YAP and TAZ oncoproteins confer malignancy and drug resistance to various cancer types. ", "Yes-associated protein (YAP), a transcription coactivator, is the major downstream effector of the Hippo pathway, which plays a critical role in organ size control and cancer development", "YAP (Yes-associated protein) and TAZ (transcriptional coactivator with PDZ-binding motif) are major downstream effectors of the Hippo pathway that influences tissue homeostasis, organ size, and cancer development. ", "The Hippo signaling pathway converges on YAP to regulate growth, differentiation, and regeneration.", "Yes associated protein (YAP) and transcriptional co-activator with PDZ-binding motif (TAZ) are its targets and terminal effectors: inhibition of the pathway promotes YAP/TAZ translocation to the nucleus, where they interact with transcriptional enhancer associate domain (TEAD) transcription factors and coactivate the expression of target genes, promoting cell proliferation. ", "Intracellular molecules Yap, Akt, mTOR, and Erk are signaling pathway members that regulate the proliferation of tumor cells" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/26109050", "http://www.ncbi.nlm.nih.gov/pubmed/25719868", "http://www.ncbi.nlm.nih.gov/pubmed/26039999", "http://www.ncbi.nlm.nih.gov/pubmed/26125451", "http://www.ncbi.nlm.nih.gov/pubmed/26109051", "http://www.ncbi.nlm.nih.gov/pubmed/26366214", "http://www.ncbi.nlm.nih.gov/pubmed/25109332", "http://www.ncbi.nlm.nih.gov/pubmed/26199863" ]

[]

[]

[ "mDia proteins are members of the formin family." ]

[ "mDia proteins are members of the formin family" ]

[ "mDia proteins are members of the formin family of actin nucleating proteins that polymerize linear actin filaments.", "mDia1, a linear actin nucleator of the Formin family", "the mammalian Diaphanous members of the formin family of proteins (mDia) are two key players in the formation of filopodia and neurites.", "mDia proteins are mammalian homologues of Drosophila diaphanous and belong to the formin family proteins that catalyze actin nucleation and polymerization. ", " The mDia family of formins ", "interacts with the formin protein mDia1 (DIAPH1).", "Formin-family proteins, in the active state, form actin-based structures such as stress fibres. Their activation mechanisms, however, are largely unknown except that mDia and its closely related formins can be activated by direct binding of the small GTPase Rho or Cdc42.", "Mouse Diaphanous-related formins (mDias) are members of the formin protein family that nucleate actin polymerization and subsequently promote filamentous actin (F-actin) elongation by monomer addition to fast-growing barbed ends.", "Diaphanous related formins (DRFs) are part of the formin protein family that control morphogenesis, embryonic differentiation, cytokinesis, and cell polarity.", "Diaphanous related formins (DRFs) are cytoskeleton remodeling proteins that mediate specific upstream GTPase signals to regulate cellular processes such as cytokinesis, cell polarity, and organelle motility. " ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/18230650", "http://www.ncbi.nlm.nih.gov/pubmed/24333164", "http://www.ncbi.nlm.nih.gov/pubmed/24025634", "http://www.ncbi.nlm.nih.gov/pubmed/16487696", "http://www.ncbi.nlm.nih.gov/pubmed/23721065", "http://www.ncbi.nlm.nih.gov/pubmed/24563699", "http://www.ncbi.nlm.nih.gov/pubmed/19160018", "http://www.ncbi.nlm.nih.gov/pubmed/11509578", "http://www.ncbi.nlm.nih.gov/pubmed/21930699", "http://www.ncbi.nlm.nih.gov/pubmed/24242070", "http://www.ncbi.nlm.nih.gov/pubmed/18362183", "http://www.ncbi.nlm.nih.gov/pubmed/14765113", "http://www.ncbi.nlm.nih.gov/pubmed/14519394", "http://www.ncbi.nlm.nih.gov/pubmed/11591323", "http://www.ncbi.nlm.nih.gov/pubmed/16361707", "http://www.ncbi.nlm.nih.gov/pubmed/16303559", "http://www.ncbi.nlm.nih.gov/pubmed/8144827", "http://www.ncbi.nlm.nih.gov/pubmed/17682067", "http://www.ncbi.nlm.nih.gov/pubmed/18239683", "http://www.ncbi.nlm.nih.gov/pubmed/16361249", "http://www.ncbi.nlm.nih.gov/pubmed/22179776", "http://www.ncbi.nlm.nih.gov/pubmed/23060957", "http://www.ncbi.nlm.nih.gov/pubmed/12673949", "http://www.ncbi.nlm.nih.gov/pubmed/23740402", "http://www.ncbi.nlm.nih.gov/pubmed/20869367", "http://www.ncbi.nlm.nih.gov/pubmed/19768111", "http://www.ncbi.nlm.nih.gov/pubmed/10436006", "http://www.ncbi.nlm.nih.gov/pubmed/15371418", "http://www.ncbi.nlm.nih.gov/pubmed/18287523", "http://www.ncbi.nlm.nih.gov/pubmed/12857739", "http://www.ncbi.nlm.nih.gov/pubmed/15096506", "http://www.ncbi.nlm.nih.gov/pubmed/17198702", "http://www.ncbi.nlm.nih.gov/pubmed/21278336", "http://www.ncbi.nlm.nih.gov/pubmed/10629846" ]

[]

[]

[ "Yes, nucleosome eviction and chromatin remodelling depends on ATP" ]

[ "yes" ]

[ "ATP-dependent chromatin remodeling and nucleosome-depleted 'barriers' co-operate to determine the kinetics of nucleosome organization", "ATP-dependent nucleosome-remodeling factors endow chromatin with structural flexibility by promoting assembly or disruption of nucleosomes and the exchange of histone variants.", "remodeling takes place in an ATP-independent manner. Binding of distamycin to the linker and nucleosomal DNA culminates in eviction of the linker histone and the formation of a population of off-centered nucleosomes.", "which promotes histone deposition onto DNA, and a novel activity, which prevents nucleosome eviction but not remodeling mediated by the ATP-dependent RSC complex", "ATP-dependent chromatin remodeling complex SWI/SNF regulates transcription and has been implicated in promoter nucleosome eviction", "ATP-dependent nucleosome-remodeling enzyme involved in transcription, replication, and the DNA damage response", "Iec1-Ino80 complex promotes transcription through nucleosome eviction", "Ino80 complex from fission yeast mediates ATP-dependent nucleosome remodeling in vitro", "reconstitution of nucleosome disassembly using the ATP-dependent chromatin remodeler Rsc and Vps75 revealed that these proteins can cooperate to remove H2A/H2B dimers from nucleosomes.", "TP-dependent chromatin-remodeling complexes, such as RSC, can reposition, evict or restructure nucleosome", "TP-dependent chromatin remodeling complexes play a critical role in chromatin dynamics", " activity of SWI/SNF to histone eviction in trans from gene promoters." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/24068556", "http://www.ncbi.nlm.nih.gov/pubmed/19933844", "http://www.ncbi.nlm.nih.gov/pubmed/17235287", "http://www.ncbi.nlm.nih.gov/pubmed/22177115", "http://www.ncbi.nlm.nih.gov/pubmed/19470761", "http://www.ncbi.nlm.nih.gov/pubmed/19029894", "http://www.ncbi.nlm.nih.gov/pubmed/23460895", "http://www.ncbi.nlm.nih.gov/pubmed/20513433", "http://www.ncbi.nlm.nih.gov/pubmed/24008565" ]

[]

[ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0000786", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0006337", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009707", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D000255" ]

[ "TREM2 variants have been found to be associated with early as well as with late onset Alzheimer's disease." ]

[ "yes" ]

[ "Genetic deficits and loss of function for the triggering receptor expressed in myeloid cells 2 (TREM2; encoded at chr6p21.1), a transmembrane spanning stimulatory receptor of the immunoglobulin/lectin-like gene superfamily, have been associated with deficiencies in phagocytosis and the innate immune system in Alzheimer's disease.", "Recent works have demonstrated a rare functional variant (R47H) in triggering receptor expressed on myeloid cells (TREM) 2 gene, encoding TREM2 protein, increase susceptibility to late-onset Alzheimer's disease (AD),", "possible involvement of TREM2 in AD pathogenesis.", "TREM2 is associated with the risk of Alzheimer's disease in Spanish population.", "Two recent studies have reported the association of rs75932628-T in the TREM2 gene with the risk for Alzheimer's disease (AD).", "we report the first positive replication study in a Spanish population and confirm that TREM2 rs75932628-T is associated with the risk for AD.", "(TREM2) has recently been identified as a rare risk factor for late-onset Alzheimer's disease (AD).", "In this study we examined the association between TREM2 exon 2 variants and early-onset AD in a sample of Caucasian subjects of French origin including 726 patients with age of onset ≤65 years and 783 controls.", "We found significantly more variants in exon 2 of TREM2 in patients with Alzheimer's disease than in controls in the discovery set", "The most commonly associated variant, rs75932628 (encoding R47H), showed highly significant association with Alzheimer's disease (P<0.001).", "Our findings strongly implicate variant TREM2 in the pathogenesis of Alzheimer's disease. Given the reported antiinflammatory role of TREM2 in the brain, the R47H substitution may lead to an increased predisposition to Alzheimer's disease", "Recent works have demonstrated a rare functional variant (R47H) in triggering receptor expressed on myeloid cells (TREM) 2 gene, encoding TREM2 protein, increase susceptibility to late-onset Alzheimer's disease (AD), with an odds ratio similar to that of the apolipoprotein E ε4 allele.", "The rs75932628-T variant of the gene encoding the triggering receptor expressed on myeloid cells 2 (TREM2) has recently been identified as a rare risk factor for late-onset Alzheimer's disease (AD).", "BACKGROUND: Homozygous loss-of-function mutations in TREM2, encoding the triggering receptor expressed on myeloid cells 2 protein, have previously been associated with an autosomal recessive form of early-onset dementia.", "CONCLUSIONS: Heterozygous rare variants in TREM2 are associated with a significant increase in the risk of Alzheimer's disease.", "RESULTS: A rare missense mutation (rs75932628-T) in the gene encoding the triggering receptor expressed on myeloid cells 2 (TREM2), which was predicted to result in an R47H substitution, was found to confer a significant risk of Alzheimer's disease in Iceland (odds ratio, 2.92; 95% confidence interval [CI], 2.09 to 4.09; P=3.42×10(-10))." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/23391427", "http://www.ncbi.nlm.nih.gov/pubmed/23462268", "http://www.ncbi.nlm.nih.gov/pubmed/23150908", "http://www.ncbi.nlm.nih.gov/pubmed/17088018", "http://www.ncbi.nlm.nih.gov/pubmed/23407992", "http://www.ncbi.nlm.nih.gov/pubmed/23380991", "http://www.ncbi.nlm.nih.gov/pubmed/23150934" ]

[ { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#type", "s": "http://linkedlifedata.com/resource/#_45325250343700D", "o": "http://purl.uniprot.org/core/Gene" } ]

[ "http://www.uniprot.org/uniprot/TREM2_HUMAN", "http://www.disease-ontology.org/api/metadata/DOID:10652", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D000544" ]

[ "The concept of a genomic signature was introduced with the observation of species-type specific Dinucleotide Relative Abundance Profiles (DRAPs). The set of dinucleotide odds ratios or 'general design' is a remarkably stable property of the DNA of an organism, and can be used to discriminate between sequences from different organisms. The average absolute dinucleotide relative abundance difference is termed delta-distance. Delta-distance is the most commonly used measure of differences bwetween \"genomic signatures\". Delta-distances between different genomic sequences in the same species are low, and are generally smaller than the between-species delta-distances." ]

[ "delta-distance" ]

[ "The average absolute dinucleotide relative abundance difference, termed delta-distance, has been commonly used to measure differences in dinucleotide composition, or 'genomic signature',", "the concept of a genomic signature was introduced with the observation of species-type specific Dinucleotide Relative Abundance Profiles (DRAPs)", "The dinucleotide relative abundance profile can be regarded as a genomic signature because, despite diversity between species, it varies little between 50 kilobase or longer windows on a given genome.", "The profile is computed from the base step \"odds ratios\" that compare dinucleotide frequencies to those expected under the assumption of stochastic equilibrium (thorough shuffling).", "The genome signatures (dinucleotide relative abundance values)", "the set of dinucleotide biases constitutes a 'genomic signature' that can discriminate sequences from different organisms.", "the set of dinucleotide odds ratio (relative abundance) values constitute a signature of each DNA genome, which can discriminate between sequences from different organisms.", "Genomic homogeneity is investigated for a broad base of DNA sequences in terms of dinucleotide relative abundance distances (abbreviated delta-distances)", "delta-distances between different genomic sequences in the same species are low, only about 2 or 3 times the distance found in random DNA, and are generally smaller than the between-species delta-distances", "the set of dinucleotide odds ratios or 'general design' is a remarkably stable property of the DNA of an organism", "The average absolute dinucleotide relative abundance difference, termed delta-distance, has been commonly used to measure differences in dinucleotide composition, or 'genomic signature', between bacterial chromosomes and plasmids.", "The dinucleotide relative abundance profile can be regarded as a genomic signature because, despite diversity between species, it varies little between 50 kilobase or longer windows on a given genome.", "The correlation between the genomic signature and DNA-DNA hybridisation values was high and taxa that showed less than 30% DNA-DNA binding will in general not have dinucleotide relative abundance dissimilarity (delta*) values below 40.", "Previously, the concept of a genomic signature was introduced with the observation of species-type specific Dinucleotide Relative Abundance Profiles (DRAPs); dinucleotides were identified as the subsequences with the greatest bias in representation in a majority of genomes.", "Comparisons within and between species sample sequences are based on the profile of dinucleotide relative abundance values (The profile is rho*XY = f*XY/f*Xf*Y for all XY, where f*X denotes the frequency of the nucleotide X and f*XY denotes the frequency of the dinucleotide XY, both computed from the sequence concatenated with its inverted complement).", "The average absolute dinucleotide relative abundance difference, termed delta-distance, has been commonly used to measure differences in dinucleotide composition, or genomic signature, between bacterial chromosomes and plasmids.", "Comparisons within and between species sample sequences are based on the profile of dinucleotide relative abundance values (The profile is rho*XY = f*XY/f*Xf*Y for all XY, where f*X denotes the frequency of the nucleotide X and f*XY denotes the frequency of the dinucleotide XY, both computed from the sequence concatenated with its inverted complement).", "We demonstrate that the Mahalanobis distance is better than the delta-distance at measuring genomic signature differences between plasmids and chromosomes of potential hosts.", "The average absolute dinucleotide relative abundance difference, termed delta-distance, has been commonly used to measure differences in dinucleotide composition, or 'genomic signature', between bacterial chromosomes and plasmids.", "The average absolute dinucleotide relative abundance difference, termed delta-distance, has been commonly used to measure differences in dinucleotide composition, or 'genomic signature', between bacterial chromosomes and plasmids", "Previously, the concept of a genomic signature was introduced with the observation of species-type specific Dinucleotide Relative Abundance Profiles (DRAPs); dinucleotides were identified as the subsequences with the greatest bias in representation in a majority of genomes" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/12171605", "http://www.ncbi.nlm.nih.gov/pubmed/15046306", "http://www.ncbi.nlm.nih.gov/pubmed/15716010", "http://www.ncbi.nlm.nih.gov/pubmed/9294192", "http://www.ncbi.nlm.nih.gov/pubmed/10430918", "http://www.ncbi.nlm.nih.gov/pubmed/9190805", "http://www.ncbi.nlm.nih.gov/pubmed/7482779", "http://www.ncbi.nlm.nih.gov/pubmed/10066522", "http://www.ncbi.nlm.nih.gov/pubmed/7809131", "http://www.ncbi.nlm.nih.gov/pubmed/18953039" ]

[]

[]

[ "Immunoaffinity purification using specific antibodies has been used in order to perform enrichment of methylated peptides." ]

[ "Immunoaffinity purification" ]

[ "To better study protein methylation, we have developed highly specific antibodies against monomethyl arginine; asymmetric dimethyl arginine; and monomethyl, dimethyl, and trimethyl lysine motifs. These antibodies were used to perform immunoaffinity purification of methyl peptides followed by LC-MS/MS analysis to identify and quantify arginine and lysine methylation sites in several model studies. " ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/24129315" ]

[]

[ "http://www.biosemantics.org/jochem#4275376", "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=D001120", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D008745" ]

[ "N-terminal proteomics allows the systematic identification of protease/peptidase cleavage events revealing substrate cleavage specificities." ]

[]

[ "ChaFRADIC is a powerful and practicable tool for protease and peptidase research,", "systematic identification of protease cleavage events by quantitative N-terminal proteomics,", " identifying the largest set of protein protease substrates ever reported and gaining novel insight into substrate specificity differences of these cathepsins.", "new insights into the structure-function relationship of protease targets and their validation from large-scale approaches.", "revealed unknown cleavage specificities, uncharacterized extended specificity profiles, and macromolecular determinants in substrate selection that were confirmed by molecular modeling. " ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/23745983", "http://www.ncbi.nlm.nih.gov/pubmed/19767749", "http://www.ncbi.nlm.nih.gov/pubmed/22065552", "http://www.ncbi.nlm.nih.gov/pubmed/18836177", "http://www.ncbi.nlm.nih.gov/pubmed/20627866", "http://www.ncbi.nlm.nih.gov/pubmed/23964590" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D020543", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D040901" ]

[ "System biology combines various omics technologies such as genomics, transcriptomics, proteomics, metabolomics, epigenomics, glucomics, degradomics and fluxomics." ]

[ "genomics", "transcriptomics", "proteomics", "metabolomics", "degradomics", "fluxomics", "epigenomics", "glucomics" ]

[ "The increasing role of metabolomics in system biology is driving the development of tools for comprehensive analysis of high-resolution NMR spectral datasets.", "Proteomics technology, a major component of system biology, has gained comprehensive attention in the area of medical diagnosis, drug development, and mechanism research.", "Metabolomics complements other omics, such as transcriptomics and proteomics and since it is a 'downstream' result of gene expression, changes in the metabolome is considered to best reflect the activities of the cell at a functional level. ", "In addition, integrated applications with genomics, transcriptomics, and proteomics provide greater understanding of global system biology.", "From proteomics to integrated omics towards system biology.", "In recent years, in the post genomic era, more and more data is being generated by biological high throughput technologies, such as proteomics and transcriptomics. ", "Glycomics meets genomics, epigenomics and other high throughput omics for system biology studies.", "The current state-of-the-art in high-throughput glycomics and its integration with genomics, epigenomics and lipidomics is reviewed in this article.", "The resulting lists of metabolites and their steady state concentrations in combination with transcriptomics can be used in system biology approaches.", "all system biology aspects (genomics, transcriptomics, proteomics, metabolomics, degradomics and fluxomics). ", "Recent development in high-throughput methods enables analysis of genome, transcriptome, proteome, and metabolome at an unprecedented scale, thus contributing to the deluge of experimental data in numerous public databases. " ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/23294434", "http://www.ncbi.nlm.nih.gov/pubmed/23287290", "http://www.ncbi.nlm.nih.gov/pubmed/26557869", "http://www.ncbi.nlm.nih.gov/pubmed/23369275", "http://www.ncbi.nlm.nih.gov/pubmed/22221061", "http://www.ncbi.nlm.nih.gov/pubmed/23137709", "http://www.ncbi.nlm.nih.gov/pubmed/24957891", "http://www.ncbi.nlm.nih.gov/pubmed/16895927", "http://www.ncbi.nlm.nih.gov/pubmed/23256674" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D049490" ]

[ "Rindopepimut is an analog of EGFRvIII. It is being tested for treatment of glioblastoma multiforme", "Rindopepimut is a peptide vaccine which elicits EGFRvIII-specific humoral and cellular immune responses. " ]

[ "EGFRvIII" ]

[ "Rindopepimut consists of a 14-mer peptide that spans the length of EGF receptor variant III, a mutant variant of EGF receptor found on approximately 30% of primary GBM, conjugated to the carrier protein keyhole limpet hemocyanin.", "Rindopepimut is a peptide vaccine which elicits EGFRvIII-specific humoral and cellular immune responses. ", "A peptide vaccine, rindopepimut (CDX-110, Celldex Therapeutics), is directed against the novel exon 1-8 junction produced by the EGFRvIII deletion, and it has shown high efficacy in preclinical models. ", "Rindopepimut, a 14-mer injectable peptide vaccine against EGFRvIII for the potential treatment of glioblastoma multiforme.", "Rindopepimut specifically targets a novel junctional epitope of the EGFR deletion mutant EGFRvIII, which is a constitutively active receptor that is expressed in approximately 60 to 70% of patients with GBM. ", "A peptide vaccine, rindopepimut (CDX-110, Celldex Therapeutics), is directed against the novel exon 1-8 junction produced by the EGFRvIII deletion, and it has shown high efficacy in preclinical models", "Rindopepimut is a peptide vaccine which elicits EGFRvIII-specific humoral and cellular immune responses" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/25186601", "http://www.ncbi.nlm.nih.gov/pubmed/23055947", "http://www.ncbi.nlm.nih.gov/pubmed/22309662", "http://www.ncbi.nlm.nih.gov/pubmed/21154166" ]

[]

[ "http://www.uniprot.org/uniprot/GRFA_CAMPM", "http://www.uniprot.org/uniprot/GRFA_RFVKA", "http://www.uniprot.org/uniprot/GRFA_RABPU", "http://www.uniprot.org/uniprot/GRFA_MYXVL", "http://www.uniprot.org/uniprot/GRFA_CAMPS" ]

[ "The gene mutations that have been shown to be the causes of isolated non-compaction cardiomyopathy are alpha-tropomyosin, alpha-tropomyosin, troponin T and desmoplakin", "cardiac β-myosin heavy chain gene (MYH7)\nc.349G>A (p.D117N) in the ZASP gene\nmutation in the isoform-1 specific region of the DSP C-terminus\npE96K mutation in the cardiac troponin T gene (TNNT2)" ]

[ "alpha-tropomyosin", "TPM1", "β-myosin heavy chain", "MYH7", "troponin T", "TNNT2", "pE96K mutation", "Desmoplakin", "DSP", "mutation in the isoform-1 specific region of the DSP C-terminus", "mindbomb homolog 1", "MIB1", "c.349G>A (p.D117N) in the ZASP gene" ]

[ "A novel alpha-tropomyosin mutation associates with dilated and non-compaction cardiomyopathy", "We show that a mutation in TPM1 is associated with DCM and a lethal, early onset form of NCCM", "Mutation in MYH7B causes a classical LVNC phenotype", "We report on two prenatal ultrasound diagnoses of left ventricular non-compaction cardiomyopathy (LVNC) associated with mutation of the cardiac β-myosin heavy chain gene (MYH7)", "This novel homozygous truncating mutation in the isoform-1 specific region of the DSP C-terminus caused Carvajal syndrome comprising severe early-onset heart failure with features of non-compaction cardiomyopathy", "Severe familial left ventricular non-compaction cardiomyopathy due to a novel troponin T (TNNT2) mutation", "we describe a family with LVNC due to a novel missense mutation, pE96K, in the cardiac troponin T gene", "We describe, in two separate autosomal-dominant NCCM families, the identification of mutations in the sarcomeric cardiac beta-myosin heavy chain gene (MYH7)", "the molecular classification of cardiomyopathies includes an MYH7-associated spectrum of NCCM" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/21285074", "http://www.ncbi.nlm.nih.gov/pubmed/18159245", "http://www.ncbi.nlm.nih.gov/pubmed/23147248", "http://www.ncbi.nlm.nih.gov/pubmed/19438153", "http://www.ncbi.nlm.nih.gov/pubmed/14662268", "http://www.ncbi.nlm.nih.gov/pubmed/21604106", "http://www.ncbi.nlm.nih.gov/pubmed/20083571", "http://www.ncbi.nlm.nih.gov/pubmed/20542340", "http://www.ncbi.nlm.nih.gov/pubmed/21551322", "http://www.ncbi.nlm.nih.gov/pubmed/20386670", "http://www.ncbi.nlm.nih.gov/pubmed/23314057", "http://www.ncbi.nlm.nih.gov/pubmed/23074372", "http://www.ncbi.nlm.nih.gov/pubmed/18395448", "http://www.ncbi.nlm.nih.gov/pubmed/17101628", "http://www.ncbi.nlm.nih.gov/pubmed/22619057", "http://www.ncbi.nlm.nih.gov/pubmed/23800289", "http://www.ncbi.nlm.nih.gov/pubmed/19467449", "http://www.ncbi.nlm.nih.gov/pubmed/19028670", "http://www.ncbi.nlm.nih.gov/pubmed/22859017", "http://www.ncbi.nlm.nih.gov/pubmed/17956225", "http://www.ncbi.nlm.nih.gov/pubmed/24015429", "http://www.ncbi.nlm.nih.gov/pubmed/21894393", "http://www.ncbi.nlm.nih.gov/pubmed/21789513", "http://www.ncbi.nlm.nih.gov/pubmed/17947214" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D056830", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009202", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009154", "http://www.disease-ontology.org/api/metadata/DOID:0050700", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005796" ]

[ "Non-small cell lung cancer (NSCLC) cell line NCI-H520. \nSquamous cell carcinoma cell line NCI-H520.", "The NCI-H520 cell-line is derived from human non-small cell lung cancer tissue." ]

[ "Squamous cell carcinoma", "Non-small cell lung cancer", "Lung" ]

[ "The nanostructures target the cells with high affinity and specificity via the specific interaction between the aptamer (a 45-base oligonucleotide) and the cell, and distinguish A549 cells from other types of cancer cells (HeLa and MCF-7 cells) and subtypes of lung cancer cells (NCI-H157, NCI-H520, NCI-H1299, and NCI-H446 cells). ", "Functional studies in A549 bronchioalveolar carcinoma and NCI-H520 squamous cell carcinoma cells revealed that Msi1 was enriched in spheroid cultures of tumor cells and in the CD133+ cell population. ", "BHLHB3 gene overexpression inhibited colony formation of A549, NCI-H520 and NCI-H596 lung cancer cells. ", "Cellular proliferation was inhibited in non-small cell lung cancer (NSCLC) cell lines NCI-H460, NCI-H520, NCI-H1299, and SK-MES-1 by CTGF overexpression.", "Human NCI-H520 cancer cells transfected with PDCD5 cDNA showed decreased colony-forming ability. ", "In 4 lung cancer cell strains, BNIP3L protein was not detected in A549, NCI-H460, NCI-H446, except for NCI-H520, in which the protein expression level was slightly lower than that in immortal bronchial epithelial cell strain HBE4-E6/E7.", "We show that CLN3 mRNA and protein are overexpressed in glioblastoma (U-373G and T98g), neuroblastoma (IMR-32 and SK-N-MC), prostate (Du145, PC-3, and LNCaP), ovarian (SK-OV-3, SW626, and PA-1), breast (BT-20, BT-549, and BT-474), and colon (SW1116, SW480, and HCT 116) cancer cell lines but not in pancreatic (CAPAN and As-PC-1) or lung (A-549 and NCI-H520) cancer cell lines.", "NSCLC cell lines NCI-H520 and H460, which have no endogenous Cyr61, formed 60-90% fewer colonies after being transfected with a Cyr61 cDNA expression vector than cells transfected with the same amount of empty vector.", "Importantly, the non-small cell lung carcinoma cell lines expressed either liver-specific (non-neuronal) mRNA (cell line A549) or predominantly the neuronal (cell line NCI-H520) AADC message. ", "The antitumor effect of CGP41251 (4'-N-benzoyl staurosporine), a selective protein kinase C (PKC) inhibitor, was examined on two kinds of human non-small cell lung cancer (NSCLC) cell lines (adenocarcinoma: A549 and squamous cell carcinoma: NCI-H520)." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/20219072", "http://www.ncbi.nlm.nih.gov/pubmed/8822090", "http://www.ncbi.nlm.nih.gov/pubmed/23489803", "http://www.ncbi.nlm.nih.gov/pubmed/12702576", "http://www.ncbi.nlm.nih.gov/pubmed/14965369", "http://www.ncbi.nlm.nih.gov/pubmed/15750352", "http://www.ncbi.nlm.nih.gov/pubmed/12964003", "http://www.ncbi.nlm.nih.gov/pubmed/9099905", "http://www.ncbi.nlm.nih.gov/pubmed/16798224", "http://www.ncbi.nlm.nih.gov/pubmed/16820889", "http://www.ncbi.nlm.nih.gov/pubmed/14586397", "http://www.ncbi.nlm.nih.gov/pubmed/16462760", "http://www.ncbi.nlm.nih.gov/pubmed/12851688", "http://www.ncbi.nlm.nih.gov/pubmed/16549820", "http://www.ncbi.nlm.nih.gov/pubmed/17600088", "http://www.ncbi.nlm.nih.gov/pubmed/14720367", "http://www.ncbi.nlm.nih.gov/pubmed/18223678", "http://www.ncbi.nlm.nih.gov/pubmed/16877704", "http://www.ncbi.nlm.nih.gov/pubmed/23715514", "http://www.ncbi.nlm.nih.gov/pubmed/19968287", "http://www.ncbi.nlm.nih.gov/pubmed/11830536", "http://www.ncbi.nlm.nih.gov/pubmed/22562359", "http://www.ncbi.nlm.nih.gov/pubmed/19700217", "http://www.ncbi.nlm.nih.gov/pubmed/9492037", "http://www.ncbi.nlm.nih.gov/pubmed/15007389", "http://www.ncbi.nlm.nih.gov/pubmed/15254679", "http://www.ncbi.nlm.nih.gov/pubmed/18502124", "http://www.ncbi.nlm.nih.gov/pubmed/9616291", "http://www.ncbi.nlm.nih.gov/pubmed/24040647", "http://www.ncbi.nlm.nih.gov/pubmed/12680874", "http://www.ncbi.nlm.nih.gov/pubmed/11598125" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D002460", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D002461", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D014024", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D045744", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D054547" ]

[ "Yes, different members of the Polycomb family have been found mutated in diseases such as primary microcephaly, nonsyndromic cleft lip and several cancers (including hemotopoietic malignancies, esophageal carcinoma, head and neck cancer or prostate cancer).\n\nExact anser:\nYes" ]

[ "yes" ]

[ "We identify a novel mutation in PHC1, a human orthologue of the Drosophila polyhomeotic member of polycomb group (PcG), which significantly decreases PHC1 protein expression, increases Geminin protein level and markedly abolishes the capacity to ubiquitinate histone H2A in patient cells.", "In clinical specimens of head and neck cancer, we found that coamplification of BMI1 and AURKA correlated with poorer prognosis.", "Mutations of EZH2, RUNX1, TP53, and ASXL1 were associated with shorter overall survival independent of the LR-PSS.", "In this study, we show the high frequency of spontaneous γδ T-cell leukemia (T-ALL) occurrence in mice with biallelic deletion of enhancer of zeste homolog 2 (Ezh2).", "Subsequently, analysis of deletion profiles of other PRC2 members revealed frequent losses of genes such as EZH2, AEBP2, and SUZ12; however, the deletions targeting these genes were large. We also identified two patients with homozygous losses of JARID2 and AEBP2. We observed frequent codeletion of AEBP2 and ETV6, and similarly, SUZ12 and NF1.", "A total of 25 different EZH2 mutations were detected in 5.9% of PMF, 1.2% of PPV-MF, and 9.4% of PET-MF patients; most were exonic heterozygous missense changes.", "In the present investigation we have focused on the candidate region in 6p23, a region that have been found linked to CL/P in several investigations, in the attempt to find out the susceptibility gene provisionally named OFC1. Gene expression experiments in mice embryo of positional candidate genes revealed that JARID2 was highly and specifically expressed in epithelial cells in merging palatal shelves.", "High expression of EZH2 and amplification of EZH2 was found in 54.1% and 12.0% of ESCCs, respectively.", "We also observed that HOXA9 levels were significantly inversely correlated with survival and that BMI-1 was overexpressed in cases with 11q23 rearrangements, suggesting that p19(ARF) suppression may be involved in MLL-associated leukemia.", "We demonstrate that in multiple experimental models of metastatic prostate cancer both BMI1 and Ezh2 genes are amplified and gene amplification is associated with increased expression of corresponding mRNAs and proteins.", "he EZH2 gene amplification was significantly (P < 0.05) associated with increased EZH2 protein expression.", "The third tumor showed a t(6p;10q;10p) as the sole karyotypic abnormality, leading to the fusion of PHF1 with another partner, the enhancer of polycomb (EPC1) gene from 10p11; EPC1 has hitherto not been associated with neoplasia." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/22869879", "http://www.ncbi.nlm.nih.gov/pubmed/23204235", "http://www.ncbi.nlm.nih.gov/pubmed/23418308", "http://www.ncbi.nlm.nih.gov/pubmed/20506229", "http://www.ncbi.nlm.nih.gov/pubmed/18668134", "http://www.ncbi.nlm.nih.gov/pubmed/16397222", "http://www.ncbi.nlm.nih.gov/pubmed/16575874", "http://www.ncbi.nlm.nih.gov/pubmed/22328940", "http://www.ncbi.nlm.nih.gov/pubmed/22190018", "http://www.ncbi.nlm.nih.gov/pubmed/16963837", "http://www.ncbi.nlm.nih.gov/pubmed/22237151", "http://www.ncbi.nlm.nih.gov/pubmed/19904743", "http://www.ncbi.nlm.nih.gov/pubmed/22431509", "http://www.ncbi.nlm.nih.gov/pubmed/21921040" ]

[]

[ "http://www.uniprot.org/uniprot/PC_DROME", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0031519" ]

[ "Drisapersen is a 2'-O-methyl-phosphorothioate oligonucleotide designed to skip exon 51 in dystrophin pre-mRNA to restore the reading frame of the mRNA. It has potential for treatment of Duchenne muscular dystrophy." ]

[]

[ "Drisapersen is a 2'-O-methyl-phosphorothioate oligonucleotide designed to skip exon 51 in dystrophin pre-mRNA to restore the reading frame of the mRNA. ", "UNLABELLED: Chronic administration of drisapersen, a 2'-OMe phosphorothioate antisense oligonucleotide (AON) to mice and monkeys resulted in renal tubular accumulation, with secondary tubular degeneration.", "Currently, the most promising potential drugs are the exon-skipping agents eteplirsen and drisapersen.", "Currently, the most promising potential drugs are the exon-skipping agents eteplirsen and drisapersen", "Drisapersen is a 2'-O-methyl-phosphorothioate oligonucleotide designed to skip exon 51 in dystrophin pre-mRNA to restore the reading frame of the mRNA", "Fast forward 25 years, and two phase 2b/3 trials have been carried out with agents designed to induce de novo dystrophin production in DMD patient's muscle; ataluren (stop codon read through) with 174 patients, and drisapersen (exon skipping) with 186 patients" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/25209738", "http://www.ncbi.nlm.nih.gov/pubmed/24292388", "http://www.ncbi.nlm.nih.gov/pubmed/24620745", "http://www.ncbi.nlm.nih.gov/pubmed/23995279", "http://www.ncbi.nlm.nih.gov/pubmed/24321374", "http://www.ncbi.nlm.nih.gov/pubmed/24229740" ]

[]

[]

[ "miRNA 29 is involved in post-ischemic myocardial remodeling in particular in the peri-infarctual zone. miRNA 29 produces apoptosis and enhances fibrotic response." ]

[ "yes" ]

[ "Myocardial ischaemia/reperfusion (I/R)-induced remodelling generally includes cell death (necrosis and apoptosis), myocyte hypertrophy, angiogenesis, cardiac fibrosis, and myocardial dysfunction. I", "In addition, miR-21, -24, -133, -210, -494, and -499 appear to protect myocytes against I/R-induced apoptosis, whereas miR-1, -29, -199a, and -320 promote apoptosis", "Myocardial fibrosis can be regulated by the miR-29 family", "Studies using various in vivo, ex vivo, and in vitro models have suggested the possible involvement of miR-1, miR-21, miR-29, miR-92a, miR-133, miR-199a, and miR-320 in ischemia-reperfusion injury and/or remodeling after myocardial infarction.", "Among the MI-regulated miRNAs are members of the miR-29 family, which are down-regulated in the region of the heart adjacent to the infarct. The miR-29 family targets a cadre of mRNAs that encode proteins involved in fibrosis, including multiple collagens, fibrillins, and elastin. Thus, down-regulation of miR-29 would be predicted to derepress the expression of these mRNAs and enhance the fibrotic response. Indeed, down-regulation of miR-29 with anti-miRs in vitro and in vivo induces the expression of collagens, whereas over-expression of miR-29 in fibroblasts reduces collagen expression. We conclude that miR-29 acts as a regulator of cardiac fibrosis and represents a potential therapeutic target for tissue fibrosis in general." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/20971881", "http://www.ncbi.nlm.nih.gov/pubmed/20959496", "http://www.ncbi.nlm.nih.gov/pubmed/22038740", "http://www.ncbi.nlm.nih.gov/pubmed/20733099", "http://www.ncbi.nlm.nih.gov/pubmed/18723672" ]

[]

[ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0035196", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0010586", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0010587", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D020257", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D035683" ]

[ "Between 0.125 and 39 in every 1000 live births. Most probably 1:5000 of live-born." ]

[ "1:5000" ]

[ "dwards syndrome (trisomy 18) occurs in 1: 8000 live births and is closely related to the mother's age", "Mean incidence was 390.06 (449.08 in boys and 327.93 in girls) per 10 000 live births", "The incidence of Edwards syndrome is 1:5000 of live-born", "The OR for Patau syndrome was 1.10 (95% CI 0.83 to 1.45); for Edwards syndrome, 1.15 (0.96 to 1.38); for Klinefelter syndrome, 1.35 (1.02 to 1.79); and for XYY syndrome, 1.99 (0.75 to 5.26)", "The live birth prevalence in the absence of prenatal screening and selective termination in England and Wales from 1997 to 2004 was 1.4 (95% CI: 1.2-1.6) per 10 000 births for trisomy 13 and 2.3 (95% CI: 2.1-2.5) for trisomy 18", "During the period under the study, following total numbers, mean relative incidences (per 10,000 live births, in brackets) and mean prenatal diagnostics efficiency (in %) were found in following chromosomal syndromes: Down syndrome 2,244 (16.58) and 63.37%, Edwards syndrome 521 (3.85) and 79.93%, Patau syndrome 201 (1.49) and 68.87%, Turner syndrome 380 (2.81) and 79.89%, 47,XXX syndrome 61 (0.45) and 59.74%, Klinefelter syndrome 163 (1.20) and 73.65% and 47,XYY syndrome 22 (0.16) and 54.76%", "There was evidence of space-time clustering for Down syndrome (fixed threshold of close in space: P = 0.01, NN threshold: P = 0.02), but little or no clustering for Patau (P = 0.57, P = 0.19) or Edwards (P = 0.37, P = 0.06) syndromes. ", "Of the 49,806 pregnant women between 15 and 23 weeks' gestational age who received prenatal serum screening with a cut-off value (a risk of 1:270 for Down and 1:100 for Edwards syndrome), 2,116 (4.2%) and 196 (0.4%) were screen positive for Down syndrome and for Edwards syndrome, respectively.", "26,803 of the 27,313 women (98%) were screened. The average was 25.1, and 1.7% of them were over 35. Serum screening showed that 1,244 (5%) were Down syndrome positive and 105 (0.4%) were Edwards syndrome positive.", "235 pregnancies of women delivered in units in the North West Thames region over a two-year period (1990-91) whose babies or fetuses were diagnosed as having Down, Edwards or Patau syndrome. RESULTS: 33% of Down syndrome, 68% of Edwards syndrome and 52% of Patau syndrome were diagnosed prenatally (before 28 weeks) in the region without the use of serum screening. " ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/19911411", "http://www.ncbi.nlm.nih.gov/pubmed/18467377", "http://www.ncbi.nlm.nih.gov/pubmed/20584846", "http://www.ncbi.nlm.nih.gov/pubmed/18067809", "http://www.ncbi.nlm.nih.gov/pubmed/18156713", "http://www.ncbi.nlm.nih.gov/pubmed/21786507", "http://www.ncbi.nlm.nih.gov/pubmed/23421080", "http://www.ncbi.nlm.nih.gov/pubmed/19408854", "http://www.ncbi.nlm.nih.gov/pubmed/8248469", "http://www.ncbi.nlm.nih.gov/pubmed/23116348" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D015994", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D014314", "http://www.disease-ontology.org/api/metadata/DOID:1085" ]

[ "In eukaryotic cells, XRN1 is often found in particles known as processing bodies (P bodies) together with other proteins involved in the 5' → 3' degradation pathway, such as DCP2 and the helicase DHH1 (Me31B). In yeast and human tissue culture cells, Xrn1 has been shown to be a component of P-bodies (processing bodies), dynamic cytoplasmic granules where RNA degradation can take place. Many P-body components including LSM1, GW182, DDX3, DDX6 and XRN1, but not others like DCP1a and EDC4 are recruited to the viral replication sites, as evidenced by their colocalization at perinuclear region with viral NS3.", "In eukaryotic cells, degradation of bulk mRNA in the 5' to 3' direction requires the consecutive action of the decapping complex (consisting of DCP1 and DCP2) and the 5' to 3' exonuclease XRN1. These enzymes are found in discrete cytoplasmic foci known as P-bodies.", "We show that the RNA-binding protein GW182 and the DCP1:DCP2 decapping complex are required for miRNA-mediated gene silencing, uncovering a crucial role for P-body components in the miRNA pathway. An alternative pathway of mRNA degradation occurs at processing bodies, cytoplasmic foci that contain decapping enzymes, the 5'-3' exonuclease Xrn1 and the Lsm1-7 heptamer. Our results show that mammalian cells, similar to yeast, require the 5'-3' Xrn1 pathway to degrade ARE-mRNAs. Recent evidence suggests that the processing bodies may constitute specialized cellular compartments of mRNA turnover, which suggests that mRNA and protein localization may be integral to mRNA decay." ]

[ "yes" ]

[ "PBs are associated with mRNA decay and contain the decapping enzymes DCP1/2, the 5' to 3' exonuclease Xrn1, the Lsm proteins (1-7), and the scaffolding proteins hedls/GE-1 and GW182. Both SGs and PBs contain mRNA, eIF4E, microRNAs and argonaute proteins, and various regulators of mRNA stability and translation (TTP, RCK/p54, and CPEB).", "An alternative pathway of mRNA degradation occurs at processing bodies, cytoplasmic foci that contain decapping enzymes, the 5'-3' exonuclease Xrn1 and the Lsm1-7 heptamer. ", "n eukaryotic cells degradation of bulk mRNA in the 5' to 3' direction requires the consecutive action of the decapping complex (consisting of DCP1 and DCP2) and the 5' to 3' exonuclease XRN1. These enzymes are found in discrete cytoplasmic foci known as P-bodies or GW-bodies (because of the accumulation of the GW182 antigen).", "Several proteins that stimulate mRNA decapping by the Dcp1:Dcp2 complex co-localize with Dcp1 and Dcp2, together with Xrn1, a 5'-to-3' exonuclease, to structures in the cytoplasm called processing bodies. ", " On the other hand, many P-body components including LSM1, GW182, DDX3, DDX6 and XRN1, but not others like DCP1a and EDC4 are recruited to the viral replication sites, as evidenced by their colocalization at perinuclear region with viral NS3.", "We identified the Pab 1801 cytoplasmic puncta as P Bodies (PBs), which are involved in mRNA regulation. We found that, in several cell lines, including U2OS, WI38, SK-N-SH and HCT116, the Pab 1801 puncta strictly colocalize with PBs identified with specific antibodies against the PB components Hedls, Dcp1a, Xrn1 or Rck/p54.", "The core components of P-bodies, including the decapping machinery (Dcp2 and Dhh1), 5'-3' exoribonuclease (Kem1/Xrn1), and the P-body scaffolding protein (Edc3), were identified and their localizations with respect to P-bodies were demonstrated.", "The second type of granules, piP-bodies, harbors the MIWI2-TDRD9-MAEL module of the piRNA pathway and signature components of P-bodies, GW182, DCP1a, DDX6/p54, and XRN1 proteins.", "In yeast and human tissue culture cells, Xrn1 has been shown to be a component of P-bodies (processing bodies), dynamic cytoplasmic granules where RNA degradation can take place.", "Here, we show that staufen- and FMRP-containing RNPs in Drosophila neurons contain proteins also present in somatic \"P bodies,\" including the RNA-degradative enzymes Dcp1p and Xrn1p/Pacman and crucial components of miRNA (argonaute), NMD (Upf1p), and general translational repression (Dhh1p/Me31B) pathways.", " In eukaryotic cells, XRN1 is often found in particles known as processing bodies (P bodies) together with other proteins involved in the 5' → 3' degradation pathway, such as DCP2 and the helicase DHH1 (Me31B). ", "In yeast and human tissue culture cells, Xrn1 has been shown to be a component of P-bodies (processing bodies), dynamic cytoplasmic granules where RNA degradation can take place", "Owing to the essential functions of P bodies in mRNA regulation, we explored computationally the functional significance of SNPs in 7 P body components such as XRN1, DCP2, EDC3, CPEB1, GEMIN5, STAU1 and TRIM71", "The core components of P-bodies, including the decapping machinery (Dcp2 and Dhh1), 5&apos;-3&apos; exoribonuclease (Kem1/Xrn1), and the P-body scaffolding protein (Edc3), were identified and their localizations with respect to P-bodies were demonstrated", "Here, we show that staufen- and FMRP-containing RNPs in Drosophila neurons contain proteins also present in somatic &quot;P bodies,&quot; including the RNA-degradative enzymes Dcp1p and Xrn1p/Pacman and crucial components of miRNA (argonaute), NMD (Upf1p), and general translational repression (Dhh1p/Me31B) pathways", "P-body components LSM1, GW182, DDX3, DDX6 and XRN1 are recruited to WNV replication sites and positively regulate viral replication.", "The core components of P-bodies, including the decapping machinery (Dcp2 and Dhh1), 5&apos;-3&apos; exoribonuclease (Kem1/Xrn1), and the P-body scaffolding protein (Edc3), were identified and their localizations with respect to P-bodies were demonstrated. Various growth conditions, including glucose deprivation, hyperosmotic stress, and heat stress, stimulated the accumulation of P-bodies.", "Here we show that microscopically visible P-bodies are greatly diminished following West Nile viral infection, but the component proteins are not depleted. On the other hand, many P-body components including LSM1, GW182, DDX3, DDX6 and XRN1, but not others like DCP1a and EDC4 are recruited to the viral replication sites, as evidenced by their colocalization at perinuclear region with viral NS3.", "Owing to the essential functions of P bodies in mRNA regulation, we explored computationally the functional significance of SNPs in 7 P body components such as XRN1, DCP2, EDC3, CPEB1, GEMIN5, STAU1 and TRIM71. Computational analyses of non-synonymous SNPs of these components was initiated using well utilized publicly available software programs such as the SIFT, followed by PolyPhen, PANTHER, MutPred, I-Mutant-2.", "Xrn1 has been shown to be a component of P-bodies (processing bodies),", "Here, we show that hDIS3L2 is an exosome-independent cytoplasmic mRNA 3'-5' exonuclease, which exhibits processive activity on structured RNA substrates in vitro. hDIS3L2 associates with hXRN1 in an RNA-dependent manner and can, like hXRN1, be found on polysomes", "Inhibition of TAK1-JNK signaling also affected the number and size of P bodies and the localization of DCP1a, Xrn1, and Edc4.", " The organizing mechanism that forms P body foci in cells is unknown; however, potential scaffolding, aggregating, or other regulatory proteins found in P bodies were investigated for degradation. Two factors involved in 5'-end mRNA decapping and degradation, Xrn1 and Dcp1a, and the 3' deadenylase complex component Pan3 underwent accelerated degradation during infection, and Dcp1a may be a direct substrate of PV 3C proteinase.", "Secondly, P-bodies recruit mRNAs that are targeted for deadenylation and degradation by the decapping/Xrn1 pathway. ", "Depletion of TRN increased the number of P-bodies and stabilized ARE-containing mRNAs, as observed with knockdown of the 5'-3' exonuclease Xrn1.", "In this paper we show for the first time that Pacman, the Drosophila homologue of Xrn1, is localized in cytoplasmic particles in Drosophila testis cells. ", "Depletion of TRN increased the number of P-bodies and stabilized ARE-containing mRNAs, as observed with knockdown of the 5&apos;-3&apos; exonuclease Xrn1", "These structures stain positively for a number of P-body and microRNP components, a microRNA-repressed mRNA and some translational repressors. They appear more heterogeneous than P-bodies of HeLa cells, and they rarely contain the exonuclease Xrn1 but are positive for rRNA." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/19729507", "http://www.ncbi.nlm.nih.gov/pubmed/17923231", "http://www.ncbi.nlm.nih.gov/pubmed/16299471", "http://www.ncbi.nlm.nih.gov/pubmed/22383165", "http://www.ncbi.nlm.nih.gov/pubmed/20011505", "http://www.ncbi.nlm.nih.gov/pubmed/17178403", "http://www.ncbi.nlm.nih.gov/pubmed/18652574", "http://www.ncbi.nlm.nih.gov/pubmed/22590546", "http://www.ncbi.nlm.nih.gov/pubmed/16177138", "http://www.ncbi.nlm.nih.gov/pubmed/22056521", "http://www.ncbi.nlm.nih.gov/pubmed/23756462", "http://www.ncbi.nlm.nih.gov/pubmed/20962086", "http://www.ncbi.nlm.nih.gov/pubmed/23102969", "http://www.ncbi.nlm.nih.gov/pubmed/19091970", "http://www.ncbi.nlm.nih.gov/pubmed/21859862", "http://www.ncbi.nlm.nih.gov/pubmed/15901504", "http://www.ncbi.nlm.nih.gov/pubmed/20074068", "http://www.ncbi.nlm.nih.gov/pubmed/23892092" ]

[]

[]

[ "The inulinase acts on the beta-(2,1)-D-fructoside links in inulin releasing D-fructose." ]

[ "The inulinase acts on the beta-(2,1)-D-fructoside links in inulin releasing D-fructose." ]

[ "Inulinases mainly produced by the microorganism and it degrades inulin into fructose which is a digestible form. ", " Inulin or inulin-rich materials can be actively hydrolyzed by microbial inulinases to produce glucose and fructose syrups that can be used in bioprocesses.", " The catalysts treated at these conditions in both fluids were then used for the production of fructooligosaccharides (FOS) using sucrose and inulin as substrates in aqueous and organic systems.", "This work is focused on the synthesis of the fructooligosaccharides (FOS) from sucrose and inulin, using free, immobilized and pre-treated immobilized inulinase", "Using inulinases from K. marxianus NRRL Y 7571, 11.89% of GF2 and 20.83% of GF3 were obtained, using inulin as substrate. ", "TLC analysis of end product revealed that inulinase hydrolyzed inulin exclusively into fructose. ", "One product was an endo-inulinase, and the other was a β-fructofuranosidase. Both enzymes worked together to effectively degrade inulin.", "The K (m) and V (max) values of the purified enzyme for inulin were 2.3 mg/mL and 4.8 mg/min, respectively.", "Fructans were extracted from Agave salmiana juice, characterized and subjected to hydrolysis process using a commercial inulinase preparation acting freely. ", "A comparatively lower Michaelis-Menten constant (2.15 mg/ml) and higher maximum initial velocity (115 µmol/min/mg of protein) for inulinase I on inulin demonstrated the exoinulinase's greater affinity for inulin substrate.", "Inulin was hydrolyzed by the purified enzyme, yielding d-fructose as the main product. ", "The inulinase acts on the beta-(2,1)-D-fructoside links in inulin releasing D-fructose. " ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/22622836", "http://www.ncbi.nlm.nih.gov/pubmed/22286980", "http://www.ncbi.nlm.nih.gov/pubmed/23419675", "http://www.ncbi.nlm.nih.gov/pubmed/18592410", "http://www.ncbi.nlm.nih.gov/pubmed/17659392", "http://www.ncbi.nlm.nih.gov/pubmed/18065000", "http://www.ncbi.nlm.nih.gov/pubmed/23997327", "http://www.ncbi.nlm.nih.gov/pubmed/23265469", "http://www.ncbi.nlm.nih.gov/pubmed/23271628", "http://www.ncbi.nlm.nih.gov/pubmed/18663416", "http://www.ncbi.nlm.nih.gov/pubmed/24031675", "http://www.ncbi.nlm.nih.gov/pubmed/18427804", "http://www.ncbi.nlm.nih.gov/pubmed/24031804", "http://www.ncbi.nlm.nih.gov/pubmed/19107534", "http://www.ncbi.nlm.nih.gov/pubmed/18449567", "http://www.ncbi.nlm.nih.gov/pubmed/18833660", "http://www.ncbi.nlm.nih.gov/pubmed/18726619", "http://www.ncbi.nlm.nih.gov/pubmed/19514896", "http://www.ncbi.nlm.nih.gov/pubmed/17005986", "http://www.ncbi.nlm.nih.gov/pubmed/20597549", "http://www.ncbi.nlm.nih.gov/pubmed/19256341", "http://www.ncbi.nlm.nih.gov/pubmed/22629216", "http://www.ncbi.nlm.nih.gov/pubmed/18051293" ]

[]

[ "http://www.uniprot.org/uniprot/INU2_ASPFI", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0051670", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013379", "http://www.uniprot.org/uniprot/INU1_KLUMA" ]

[ "Treatment of acute myocarditis includes antiinflammatory drugs like ibuoprofen and steroids, inotropic agents and mechanical support (intra-aortic ballon pump). TandemHeart percutaneous ventricular assist device may be used in some, more compromised, patients for few days." ]

[ "antiinflammatory steroid and non steroid drugs", "inotropic agents", "mechanical support" ]

[ "ibuprofen 400 mg twice a day as therapy", "Acute fulminant myocarditis commonly manifests itself as severe, rapidly progressive hemodynamic deterioration and circulatory collapse that may be resistant to high doses of inotropic agents and steroids and to mechanical support by intra-aortic balloon pump", "the TandemHeart percutaneous ventricular assist device, can enable patients to recover in a few days.", "he authors report a typical case of fulminating myocarditis with electromechanical dissociation, which recovered completely after a period of circulatory assistance.", "To clarify the effects of Astragalus Membranaceus (AM) combined with taurine and/or coenzyme Q10(CoQ10) on coxsackievirus B3 (CVB3) murine myocarditis", "AM, taurine and CoQ10 have some curative effects on CVB3 murine myocarditis, AM combined with taurine and CoQ10 is the best." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/19214293", "http://www.ncbi.nlm.nih.gov/pubmed/11477833", "http://www.ncbi.nlm.nih.gov/pubmed/17574515", "http://www.ncbi.nlm.nih.gov/pubmed/17622371", "http://www.ncbi.nlm.nih.gov/pubmed/12055771", "http://www.ncbi.nlm.nih.gov/pubmed/20034334", "http://www.ncbi.nlm.nih.gov/pubmed/20207278" ]

[]

[]

[ "Causative genes for autosomal recessive forms of monogenic Parkinson's disease are:\nPARK2\nPARK7\nPINK1\nPARK9\nPARK14\nPARK15" ]

[ "PARK2", "PARK7", "DJ-1", "PINK1", "PARK9", "ATP13A2", "PARK14", "PLA2G6", "PARK15", "FBX07" ]

[ "Mutations in the Parkin gene (PARK2) are the major cause of autosomal recessive early-onset parkinsonism.", "Early onset PD (EOPD) is particularly associated with autosomal recessive (AR) mutations, and three genes, PARK2, PARK7 and PINK1, have been found to carry mutations leading to AR disease. ", "Homozygous or compound heterozygous mutations in the phosphatase and tensin homolog-induced putative kinase 1 (PINK1) gene are causative of autosomal recessive, early onset Parkinson's disease. ", "Mutations in other genes, including ATP13A2 (PARK9), PLA2G6 (PARK14), and FBX07 (PARK15), cause more rare forms of recessive parkinsonism with very early-onset (<30 years)", "In three forms, caused by mutations in parkin (PARK2), PINK1 (PARK6), or DJ-1 (PARK7),", "oss-of-function mutations in Parkin, PINK1, DJ-1 and ATP13A2 cause autosomal recessive parkinsonism with early-onset.", "mutations in the parkin gene, in DJ-1, PINK1 and ATP13A2 all cause autosomal-recessive parkinsonism of early onset.", "mutations in the parkin gene, in DJ-1, PINK1 and ATP13A2 cause autosomal recessive parkinsonism of early onset", "Mutations in the parkin gene, in DJ-1 and PINK1 all cause autosomal recessive parkinsonism of early onset.", "PTEN-induced putative kinase 1 (PINK1) is a causative gene for autosomal recessive early onset parkinsonism.", " we focus on PARK7, a gene relates to an autosomal recessive form of early-onset Parkinsonism and encodes a protein named DJ-1.", "PINK-1 for an autosomal-recessive early-onset variant", " Heritable mutations in alpha-synuclein, parkin, DJ-1 and PINK1 cause familial forms of PD. ", "we focus on PARK7, an autosomal recessive form of early-onset parkinsonism caused by mutations in the DJ-1 gene", "Mutations in the DJ-1 gene associated with autosomal recessive early-onset parkinsonism.", "Autosomal recessive parkinsonism associated with mutations in the parkin gene represents a monogenic form of hereditary parkinsonism.", "Mutations of the parkin gene on chromosome 6 cause autosomal recessive, early onset parkinsonism. ", " A gene causing autosomal recessive parkinsonism of juvenile onset has been mapped to chromosome 6 (PARK 2), and the causative gene has been identified and named parkin. ", "The gene responsible for AR-JP was recently identified and designated parkin." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/24167038", "http://www.ncbi.nlm.nih.gov/pubmed/18787878", "http://www.ncbi.nlm.nih.gov/pubmed/11128611", "http://www.ncbi.nlm.nih.gov/pubmed/15525661", "http://www.ncbi.nlm.nih.gov/pubmed/16003110", "http://www.ncbi.nlm.nih.gov/pubmed/18279377", "http://www.ncbi.nlm.nih.gov/pubmed/17713120", "http://www.ncbi.nlm.nih.gov/pubmed/24244333", "http://www.ncbi.nlm.nih.gov/pubmed/12446870", "http://www.ncbi.nlm.nih.gov/pubmed/10072423", "http://www.ncbi.nlm.nih.gov/pubmed/15917645", "http://www.ncbi.nlm.nih.gov/pubmed/18175395", "http://www.ncbi.nlm.nih.gov/pubmed/19168133", "http://www.ncbi.nlm.nih.gov/pubmed/21626549", "http://www.ncbi.nlm.nih.gov/pubmed/14712351", "http://www.ncbi.nlm.nih.gov/pubmed/19297401", "http://www.ncbi.nlm.nih.gov/pubmed/11911988", "http://www.ncbi.nlm.nih.gov/pubmed/22166400", "http://www.ncbi.nlm.nih.gov/pubmed/17704838", "http://www.ncbi.nlm.nih.gov/pubmed/11261251", "http://www.ncbi.nlm.nih.gov/pubmed/22166450", "http://www.ncbi.nlm.nih.gov/pubmed/17713119", "http://www.ncbi.nlm.nih.gov/pubmed/22427796", "http://www.ncbi.nlm.nih.gov/pubmed/20696312", "http://www.ncbi.nlm.nih.gov/pubmed/11487197" ]

[]

[ "http://www.disease-ontology.org/api/metadata/DOID:4", "http://www.disease-ontology.org/api/metadata/DOID:0050737", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0030849", "http://www.disease-ontology.org/api/metadata/DOID:0050739", "http://www.disease-ontology.org/api/metadata/DOID:14330", "http://www.disease-ontology.org/api/metadata/DOID:0050177", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D010300" ]

[ "Ranolazine has only a small effect on the basal calcium current, while it greatly affects whole cell calcium current when facilitated by beta-adrenoceptor or histamine receptor activation.\nRanolazine is a novel agent that inhibits the late sodium current thereby reducing cellular sodium and calcium overload.\nRanolazine reduces Ca2+ overload and LV mechanical dysfunction during ischemia/reperfusion.\nranolazine decreases I(Na,L)-induced dysregulation of calcium cycling that contributes to the antiarrhythmic actions of this agent.\nranolazine desensitizes Ca(2+)-dependent RyR2 activation, and inhibits Ca(i) oscillations.\nranolazine ameliorates the Ca(2+) response and cross-bridge kinetics of cardiac myofilaments." ]

[]

[ "Ranolazine and lidocaine (10 μM) similarly reduced Ca2+i overload and improved left ventricle work recovery in whole-heart models of IR injury or exposure to ouabain (80 μM).", "Ranolazine (10 μM), but not lidocaine (10 μM), reduced RM NCX1.1-mediated Ca2+i overload in ventricular myocytes.", "Blockade of the late inward sodium current, late I(Na), offers another target for the treatment of ischemia. Blockade of late I(Na) reduces the sodium and calcium overload that follows ischemia.", "Ranolazine, a late I(Na) inhibitor, has been shown to provide both anti-anginal and anti-ischemic benefits without significant alterations in the heart rate and blood pressure in patients with stable coronary artery disease.", "Ranolazine is a new antianginal drug that reduces intracellular sodium and calcium accumulation during ischemia, thus potentially limiting myocardial ischemia.", "Detergent extracted fiber bundles from DOCA-salt hearts demonstrated increased myofilament response to Ca(2+) with glutathionylation of myosin binding protein C. Treatment with ranolazine ameliorated the Ca(2+) response and cross-bridge kinetics.", "Ran reduces P(o) of RyR2, desensitizes Ca(2+)-dependent RyR2 activation, and inhibits Ca(i) oscillations,", "Ranolazine may provide functional protection of the heart during IR injury by reducing cCa2+ and mCa2+ loading secondary to its effect to block the late Na+ current.", "Ranolazine is a novel antianginal medication that acts by ameliorating disturbed sodium and calcium homeostasis.", "By preventing myocyte sodium and calcium overload, ranolazine also have potential beneficial effects on myocardial function.", "Reduction by RAN of I(Na,L)-induced dysregulation of calcium cycling could contribute to the antiarrhythmic actions of this agent in both reentrant and triggered arrhythmias.", "Moreover, in rabbit myocytes the increases in late I(Na), [Na(+)](i) and [Ca(2+)](i) caused by ATX-II, were significantly blunted by ranolazine. These results suggest that ranolazine may be of therapeutic benefit in conditions of diastolic dysfunction due to elevated [Na(+)](i) and diastolic [Ca(2+)](i).", "Ranolazine is a selective inhibitor of the late sodium current relative to peak sodium channel current, and via this mechanism, it may decrease sodium-dependent intracellular calcium overload during ischemia and reperfusion.", "he beneficial effects of ranolazine in reducing Ca2+ overload and LV mechanical dysfunction during ischemia/reperfusion is consistent with the inhibition of late INa mechanism of action.", "Ranolazine is a novel agent that inhibits the late sodium current thereby reducing cellular sodium and calcium overload", "Ranolazine selectively inhibits late I(Na), reduces [Na(+)](i)-dependent calcium overload and attenuates the abnormalities of ventricular repolarisation and contractility that are associated with ischaemia/reperfusion and heart failure.", "The results indicate that ranolazine, at concentrations which have significantly beneficial effects during ischaemic episodes, only greatly affects whole cell calcium current when facilitated by beta-adrenoceptor or histamine receptor activation.", "Ranolazine had only a small effect on the basal calcium current" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/21741479", "http://www.ncbi.nlm.nih.gov/pubmed/17027025", "http://www.ncbi.nlm.nih.gov/pubmed/18439620", "http://www.ncbi.nlm.nih.gov/pubmed/23247666", "http://www.ncbi.nlm.nih.gov/pubmed/17220471", "http://www.ncbi.nlm.nih.gov/pubmed/22879384", "http://www.ncbi.nlm.nih.gov/pubmed/22245792", "http://www.ncbi.nlm.nih.gov/pubmed/19675298", "http://www.ncbi.nlm.nih.gov/pubmed/23271797", "http://www.ncbi.nlm.nih.gov/pubmed/22709755", "http://www.ncbi.nlm.nih.gov/pubmed/22343711", "http://www.ncbi.nlm.nih.gov/pubmed/8735623", "http://www.ncbi.nlm.nih.gov/pubmed/16781216", "http://www.ncbi.nlm.nih.gov/pubmed/16775092", "http://www.ncbi.nlm.nih.gov/pubmed/20924097", "http://www.ncbi.nlm.nih.gov/pubmed/23596505" ]

[]

[ "http://www.uniprot.org/uniprot/CCAMK_ORYSJ", "http://www.uniprot.org/uniprot/CCAMK_LOTJA", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D002118", "http://www.disease-ontology.org/api/metadata/DOID:114", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D006331", "http://www.uniprot.org/uniprot/CCAMK_PEA", "http://www.biosemantics.org/jochem#4277675", "http://www.biosemantics.org/jochem#4268168", "http://www.biosemantics.org/jochem#4071295", "http://www.biosemantics.org/jochem#4000018", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D006321", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009206", "http://www.biosemantics.org/jochem#4260677", "http://www.biosemantics.org/jochem#4202863", "http://www.biosemantics.org/jochem#4202864", "http://www.uniprot.org/uniprot/CCAMK_LILLO" ]

[ "The conventional \"Warburg effect\" reffers to the metabolic shift of cancer cells towards aerobic glycolysis, due to mitochondrial dysfunction. The \"reverse Warburg effect\" or \"parasitic\" energy-transfer, is a model of \"two-compartment tumor metabolism\". In this model, cancer cells secrete hydrogen peroxide (H2O2), initiating oxidative stress and aerobic glycolysis in the tumor stroma. The cancer-associated fibroblasts of the stroma are glycolytic and lack detectable mitochondria. These glycolytic stromal cells produce mitochondrial fuels (L-lactate, ketone bodies and chemical building blocks, such as amino acids -glutamine-, and nucleotides) that are then transferred to oxidative epithelial cancer cells. Lactate and ketones drive cancer cell oxidative mitochondrial metabolism (OXPHOS), and building blocks sustain the anabolic needs of rapidly proliferating cancer cells. Therefore, according to the \"reverse Warburg effect\", stromal catabolism fuels anabolic tumor growth via energy transfer. Thus, in \"reverse Warburg effect\" the cancer-associated fibroblasts of the stroma undergo aerobic glycolysis, rather than epithelial cancer cells themselves, as proposed by the conventional \"Warburg effect\"." ]

[]

[ "The metabolic energy transduction pathways are strongly affected in cancers. Mitochondrial dysfunction in cancer cells (Warburg effect) or in fibroblasts associated with cancer cells (reverse Warburg effect) results in decreased or increased power of the generated electromagnetic field, respectively", "cigarette smoke induces catabolism in the local microenvironment, directly fueling oxidative mitochondrial metabolism (OXPHOS) in neighboring epithelial cancer cells, actively promoting anabolic tumor growth.", "our current findings are consistent with the idea that cigarette smoke induces the \"reverse Warburg effect,\" thereby fueling \"two-compartment tumor metabolism\" and oxidative mitochondrial metabolism in epithelial cancer cells.", "We have recently proposed a new two-compartment model for understanding the Warburg effect in tumor metabolism. In this model, glycolytic stromal cells produce mitochondrial fuels (L-lactate and ketone bodies) that are then transferred to oxidative epithelial cancer cells, driving OXPHOS and mitochondrial metabolism. Thus, stromal catabolism fuels anabolic tumor growth via energy transfer. We have termed this new cancer paradigm the \"reverse Warburg effect,\" because stromal cells undergo aerobic glycolysis, rather than tumor cells.", "Consistent with the \"reverse Warburg effect,\" our results indicate that metastatic breast cancer cells amplify oxidative mitochondrial metabolism (OXPHOS) and that adjacent stromal cells are glycolytic and lack detectable mitochondria.", "\"glycolytic\" cancer cells were rarely observed, indicating that the conventional \"Warburg effect\" does not frequently occur in cancer-positive lymph node metastases.", "We have recently proposed a new model of cancer metabolism to explain the role of aerobic glycolysis and L-lactate production in fueling tumor growth and metastasis. In this model, cancer cells secrete hydrogen peroxide (H2O2), initiating oxidative stress and aerobic glycolysis in the tumor stroma. This, in turn, drives L-lactate secretion from cancer-associated fibroblasts. Secreted L-lactate then fuels oxidative mitochondrial metabolism (OXPHOS) in epithelial cancer cells, by acting as a paracrine onco-metabolite. We have previously termed this type of two-compartment tumor metabolism the \"Reverse Warburg Effect,\" as aerobic glycolysis takes place in stromal fibroblasts, rather than epithelial cancer cells.", "the \"Reverse Warburg Effect\" or \"parasitic\" energy-transfer", "We have previously demonstrated that enhanced aerobic glycolysis and/or autophagy in the tumor stroma supports epithelial cancer cell growth and aggressive behavior, via the secretion of high-energy metabolites. These nutrients include lactate and ketones, as well as chemical building blocks, such as amino acids (glutamine) and nucleotides. Lactate and ketones serve as fuel for cancer cell oxidative metabolism, and building blocks sustain the anabolic needs of rapidly proliferating cancer cells. We have termed these novel concepts the \"Reverse Warburg Effect,\" and the \"Autophagic Tumor Stroma Model of Cancer Metabolism.", "Previously, we proposed that cancer cells behave as metabolic parasites, as they use targeted oxidative stress as a \"weapon\" to extract recycled nutrients from adjacent stromal cells. Oxidative stress in cancer-associated fibroblasts triggers autophagy and  mitophagy, resulting in compartmentalized cellular catabolism, loss of mitochondrial function, and the onset of aerobic glycolysis, in the tumor stroma. As such, cancer-associated fibroblasts produce high-energy nutrients (such as lactate and ketones) that fuel mitochondrial biogenesis, and oxidative metabolism in cancer cells. We have termed this new energy-transfer mechanism the \"reverse Warburg effect.\"", "Recently, we proposed a new mechanism for understanding the Warburg effect in cancer metabolism. In this new paradigm, cancer-associated fibroblasts undergo aerobic glycolysis, and extrude lactate to \"feed\" adjacent cancer cells, which then drives mitochondrial biogenesis and oxidative mitochondrial metabolism in cancer cells. Thus, there is vectorial transport of energy-rich substrates from the fibroblastic tumor stroma to anabolic cancer cells.", " the \"reverse Warburg effect,\" which states that cancer-associated fibroblasts undergo aerobic glycolysis, thereby producing lactate, which is utilized as a metabolic substrate by adjacent cancer cells. In this model, \"energy transfer\" or \"metabolic-coupling\" between the tumor stroma and epithelial cancer cells \"fuels\" tumor growth and metastasis, via oxidative mitochondrial metabolism in anabolic cancer cells.", "the Warburg effect in cancer cells may be due to culturing cancer cells by themselves, out of their normal stromal context or tumor microenvironment. In fact, when cancer cells are co-cultured with fibroblasts, then cancer cells increase their mitochondrial mass, while fibroblasts lose their mitochondria.", " stromal catabolism, via autophagy and mitophagy, fuels the anabolic growth of tumor cells, promoting tumor progression and metastasis. We have previously termed this new paradigm \"The Autophagic Tumor Stroma Model of Cancer Metabolism\", or the \"Reverse Warburg Effect\".", "Our findings are consistent with the recently proposed \"Reverse Warburg Effect\" and the \"Autophagic Tumor Stroma Model of Cancer Metabolism.\" In these two complementary models, cancer cells induce oxidative stress in adjacent stromal cells, which then forces these stromal fibroblasts to undergo autophagy/mitophagy and aerobic glycolysis. This, in turn, produces recycled nutrients (lactate, ketones and glutamine) to feed anabolic cancer cells, which are undergoing oxidative mitochondrial metabolism.", "cancer-associated fibroblasts undergo aerobic glycolysis and the resulting energy-rich metabolites are then transferred to epithelial cancer cells, where they enter the TCA cycle, resulting in high ATP production via oxidative phosphorylation. We have termed this new paradigm \"The Reverse Warburg Effect.\"", "Previously, we proposed a new model for understanding the Warburg effect in tumorigenesis and metastasis. In this model, the stromal fibroblasts would undergo aerobic glycolysis (a.k.a., the Warburg effect)--producing and secreting increased pyruvate/lactate that could then be used by adjacent epithelial cancer cells as \"fuel\" for the mitochondrial TCA cycle, oxidative phosphorylation, and ATP production.", "In this alternative model of tumorigenesis, the epithelial cancer cells instruct the normal stroma to transform into a wound-healing stroma, providing the necessary energy-rich micro-environment for facilitating tumor growth and angiogenesis. In essence, the fibroblastic tumor stroma would directly feed the epithelial cancer cells, in a type of host-parasite relationship. We have termed this new idea the \"Reverse Warburg Effect.\" In this scenario, the epithelial tumor cells \"corrupt\" the normal stroma, turning it into a factory for the production of energy-rich metabolites.", "Warburg's original observation that tumors show a metabolic shift towards aerobic glycolysis.", "The reverse Warburg effect: aerobic glycolysis in cancer associated fibroblasts and the tumor stroma.", "We have termed this new cancer paradigm the \"reverse Warburg effect,\" because stromal cells undergo aerobic glycolysis, rather than tumor cells.", "Thus, we conclude that ketones and lactate fuel tumor growth and metastasis, providing functional evidence to support the \"Reverse Warburg Effect\".", "We have termed this new cancer paradigm the \"reverse Warburg effect,\" because stromal cells undergo aerobic glycolysis, rather than tumor cells" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/19923890", "http://www.ncbi.nlm.nih.gov/pubmed/20818174", "http://www.ncbi.nlm.nih.gov/pubmed/22236875", "http://www.ncbi.nlm.nih.gov/pubmed/20495363", "http://www.ncbi.nlm.nih.gov/pubmed/22313602", "http://www.ncbi.nlm.nih.gov/pubmed/21300172", "http://www.ncbi.nlm.nih.gov/pubmed/25197670", "http://www.ncbi.nlm.nih.gov/pubmed/22395432", "http://www.ncbi.nlm.nih.gov/pubmed/20562527", "http://www.ncbi.nlm.nih.gov/pubmed/23388463", "http://www.ncbi.nlm.nih.gov/pubmed/21778829", "http://www.ncbi.nlm.nih.gov/pubmed/23844381", "http://www.ncbi.nlm.nih.gov/pubmed/21558814", "http://www.ncbi.nlm.nih.gov/pubmed/23443971", "http://www.ncbi.nlm.nih.gov/pubmed/21521946" ]

[]

[ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0004129" ]

[ "PER1 and PER2 genes are involved in cell cycle regulation and tumor suppression, controlling expression of genes such as c-Myc, Cyclin D1, Cyclin A, Mdm-2 and Gadd45alpha." ]

[]

[ "Temporal expression of genes involved in cell cycle regulation and tumor suppression, such as c-Myc, Cyclin D1, Cyclin A, Mdm-2 and Gadd45alpha is deregulated in mPer2 mutant mice.", "The Period (Per) genes are key circadian rhythm regulators in mammals. Expression of the mouse Per (mPer) genes have diurnal pattern in the suprachiamstic nuclei and in peripheral tissues. Genetic ablation mPER1 and mPER2 function results in a complete loss of circadian rhythm control based on wheel running activity in mice. In addition, these animals also display apparent premature aging and significant increase in neoplastic and hyperplastic phenotypes.", "Period (Per) genes are key circadian rhythm regulators in mammals. Expression of mouse Per (mPer) genes has a diurnal pattern in the suprachiasmatic nucleus and in peripheral tissues. Genetic ablation mPER1 and mPER2 function results in a complete loss of circadian rhythm control based on wheel-running activity in mice. In addition, these animals also display apparent premature aging and a significant increase in neoplastic and hyperplastic phenotypes.", "The temporal expression of genes involved in cell cycle regulation and tumor suppression, such as c-Myc, Cyclin D1, Cyclin A, Mdm-2, and Gadd45alpha, is deregulated in mPer2 mutant mice." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/16596306", "http://www.ncbi.nlm.nih.gov/pubmed/15817328" ]

[]

[ "http://www.uniprot.org/uniprot/PER1_HUMAN", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D002940", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0007623", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0032922", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0042752" ]

[ "Sorafenib induces persisten AMPK activation" ]

[ "yes" ]

[ "Here, we identify sorafenib as an activator of AMP-activated protein kinase (AMPK), in a manner that involves either upstream LKB1 or CAMKK2. ", "Persistent activation of AMPK by sorafenib finally led to the impairment of glucose metabolism both in MCF-7 and SKBR3 cells as well as in the highly glycolytic MDA-MB-231 cells, resulting in cell death.", "Here, we identify sorafenib as an activator of AMP-activated protein kinase (AMPK), in a manner that involves either upstream LKB1 or CAMKK2", "Sorafenib synergizes with metformin in NSCLC through AMPK pathway activation.", "Persistent activation of AMPK by sorafenib finally led to the impairment of glucose metabolism both in MCF-7 and SKBR3 cells as well as in the highly glycolytic MDA-MB-231 cells, resulting in cell death. This previously unrecognized long-term effect of sorafenib was mediated by AMPK-dependent inhibition of the mTORC1 pathway." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/23963659", "http://www.ncbi.nlm.nih.gov/pubmed/25080865", "http://www.ncbi.nlm.nih.gov/pubmed/25349646" ]

[]

[ "http://www.biosemantics.org/jochem#http://www.biosemantics.org/jochem#:4243524", "http://www.biosemantics.org/jochem#4243524", "http://amigo.geneontology.org/amigo/term/GO:0031588" ]

[ "The fusion protein BCR-ABL" ]

[ "BCR-ABL" ]

[ "CR-ABL-targeted TKI that inhibits BCR-ABL with greater potency compared with imatinib", "reciprocal translocation between chromosomes 9 and 22 [t(9;22)(q34;q11), Philadelphia chromosome] creates a BCR-ABL1 fusion protein", "A novel tyrosine kinase inhibitor (TKI), imatinib, has been confirmed as an effective targeted treatment in most CML patients", "The availability of tyrosine kinase inhibitors (TKIs) has considerably changed the management of Philadelphia chromosome positive leukemia. The BCR-ABL inhibitor imatinib i", "The BCR/ABL fusion tyrosine kinase is expressed in chronic myeloid leukemia and Philadelphia-positive (Ph+) acute lymphoblastic leukemia cells, and its inhibition by the clinically used tyrosine kinase inhibitors imatinib ", "Chronic myeloid leukemia (CML) is a clonal malignant myeloproliferative disorder characterized by the expansion of hematopoietic cells carrying the Philadelphia chromosome", "Patients received imatinib after diagnosis and underwent regular laboratory monitoring (quantification of BCR-ABL ratio", "CML is characterized by a balanced genetic translocation, t(9;22)(q34;q11.2), involving a fusion of the Abelson oncogene (ABL) from chromosome 9q34 with the breakpoint cluster region (BCR) gene on chromosome 22q11.2. This rearrangement is known as the Philadelphia chromosome. ", "tyrosine kinase inhibitors (TKIs), imatinib", "Characterized by a translocation between chromosomes 9 and 22, known as the Philadelphia chromosome, small-molecule tyrosine kinase inhibitors (TKIs) targeted against the oncogenic BCR-ABL fusion protein", "Chronic myelogenous leukemia (CML) and Philadelphia chromosome-positive (Ph+) acute lymphatic leukemia (Ph + ALL) are caused by the t(9;22), which fuses BCR to ABL ", "ABL-kinase inhibitors (AKIs) Imatinib", "hiladelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) is triggered by constitutively activated BCR-ABL", " BCR-ABL tyrosine kinase inhibitor imatinib ", "matinib was the first BCR-ABL tyrosine kinase inhibitor", "CML) is a pluripotent hematopoietic disorder that is currently considered incurable. The tyrosine kinase product of the Philadelphia chromosome, P210 BCR-ABL, ", "Imatinib mesylate, an orally available BCR-ABL kinase inhibitor", "Since the initial approval of imatinib much has been learned about its resistance mechanisms, and efforts have continued to improve upon BCR-ABL tyrosine kinase inhibitor therapy.", "CML) originates from a hematopoietic stem cell carrying the Philadelphia (Ph) chromosome and oncogenic BCR-ABL1 fusion gene. The first tyrosine-kinase inhibitor (TKI) imatinib ", "chronic myeloid leukemia (CML) patients ", "Philadelphia chromosome and/or BCR-ABL positive, received first-line treatment with imatinib", "matinib mesylate is the sole BCR-ABL tyrosine kinase inhibitor approved as first-line treatment of accelerated-phase (AP) chronic myeloid leukemia (CML", "Imatinib is an inhibitor of the Bcr-Abl tyrosine kinase", "Imatinib mesylate, a selective Bcr-Abl tyrosine kinase inhibitor, has revolutionized the treatment of Bcr-Abl positive chronic myeloid leukemia ", "The development of first-generation (imatinib) and second-generation (dasatinib and nilotinib) tyrosine kinase inhibitors (TKIs) that target the BCR-ABL1 fusion protein produced by the Ph chromosome revolutionized the treatment of chronic myelogenous leukemia (CML).", "The cytogenetic characteristic of Chronic Myeloid Leukemia (CML) is the formation of the Philadelphia chromosome gene product, BCR-ABL. Given that BCR-ABL is the specific target of Gleevec in CML treatment, ", "chronic myeloid leukemia (CML), BCR-ABL-mediated oncogenic signaling can be successfully targeted with the BCRABL- inhibitors imatinib", "matinib mesylate (STI 571; Gleevec; Novartis Pharmaceuticals, Basel, Switzerland) is an orally available tyrosine kinase inhibitor that targets a constitutively activated BCR-ABL tyrosine kinase", "Philadelphia chromosome positive chronic myelogenous leukemia (CML) ", "CML) is caused by the BCR-ABL oncogene. The Philadelphia chromosome (Ph) from a reciprocal translocation, t(9;22) (q34;q11) causes a fusion gene, BCR-ABL, that encodes a constitutively active tyrosine kinase. Treatment of CML by imatinib", "BCR-ABL levels", "Imatinib induces a durable response in most patients with Philadelphia chromosome-positive chronic myeloid leukemia,", "CML is a myeloproliferative disorder characterized by the presence of the Philadelphia chromosome or the BCR-ABL fusion oncogene", "imatinib therapy", "The discovery of targeted tyrosine kinase inhibition of BCR-ABL kinase dramatically changed the treatment of CML. Imatinib, the first TKI approved for treatment of patients with Philadelphia chromosome--positive CML", "CML) is a genetically associated malignancy of haematopoietic stem cells, characterized by a t(9;22) translocation that forms the Philadelphia chromosome and creates a novel fusion gene, BCR-ABL. Treatment with molecular-targeted therapy is usually initiated with imatinib", "imatinib, a selective BCR-ABL tyrosine kinase inhibitor (TKI), was started but Ph-positive chromosomes remained", "CML is induced by the BCR-ABL oncogene, whose gene product is a BCR-ABL tyrosine kinase. Currently, inhibition of BCR-ABL kinase activity by its kinase inhibitor such as imatinib mesylate (Gleevec)", "The Bcr-Abl tyrosine kinase inhibitor imatinib represented a major advance over conventional CML therapy", "Imatinib (Glivec, Gleevec), a specific small molecule inhibitor of Bcr-Abl, has become the standard drug therapy for CML,", "Imatinib blocks proliferation and induces apoptosis of BCR-ABL-expression in CML", "CML is the presence of a balanced translocation between the long arms of chromosomes 9 and 22, t(9;22)(q34;q11.2), which is known as the Philadelphia (Ph) chromosome. This translocation results in the formation of the bcr-abl fusion gene,", "emergence of imatinib", "matinib mesylate, binding to the inactive conformation of Bcr-Abl tyrosine kinase and suppressing the Ph chromosome positive clone, has revolutionized the treatment of chronic myeloid leukaemia (CML) patients.", "Ph) chromosome is the cytogenetic hallmark of chronic myeloid leukemia (CML). The translocation forms a chimeric gene, bcr-abl, which generates BCR-ABL. This fusion protein constitutively activate ABL tyrosine kinase and causes CML. Imatinib mesylate is a selective tyrosine kinase inhibitor on ABL", "CML) is characterized by the presence of a BCR-ABL fusion gene, which is the result of a reciprocal translocation between chromosomes 9 and 22, and is cytogenetically visible as a shortened chromosome 22 (Philadelphia)", "imatinib mesylate was introduced into the treatment regimen for CML", "matinib was developed as the first molecularly targeted therapy to specifically inhibit the BCR-ABL kinase in Philadelphia chromosome (Ph)-positive chronic myeloid leukemia (CML)", "hronic myelogenous leukemia is characterized by the Philadelphia-chromosome, a shortened chromosome 22 which is the result of a reciprocal translocation between chromosome 9 and 22. The fusion gene is called BCR-ABL. ", "Imatinib mesylate (Glivec) ", " BCR-ABL transcripts in the peripheral blood of patients with CML who were treated with imatinib mesylate (Glivec, Novartis)", "Imatinib was the first small molecule developed to inhibit BCR-ABL tyrosine kinase ", "hronic myeloid leukemia cells contain a BCR-ABL oncoprotein", "Imatinib mesylate, a tyrosine kinase inhibitor with specific activity against the breakpoint cluster region--Abelson murine leukemia (BCR-ABL) tyrosine kinase has been developed for treatment of chronic myelogenous leukemia (CML).", "The hallmark of CML is an acquired chromosomal translocation known as the Philadelphia chromosome (Ph), which results in the synthesis of the breakpoint cluster region-Abelson murine leukemia (BCR-ABL) fusion oncoprotein, a constitutively active tyrosine kinase. The introduction of imatinib, a tyrosine kinase inhibitor (TKI) that is specific for BCR-ABL, was a major breakthrough in CML therapy", "original TKI, imatinib", "CML were the discovery of the Philadelphia chromosome in 1960, and of the (9;22) translocation in 1973. There followed definition of the breakpoint cluster region on chromosome 22 in 1984 and the demonstration of the BCR-ABL transcript in CM", "Imatinib mesylate, a selective Bcr-Abl tyrosine kinase inhibitor, has proved to be most effective therapy of Philadelphia chromosome-positive chronic myelogenous leukemia. ", "The hallmark of CML is an acquired chromosomal translocation known as the Philadelphia chromosome (Ph) that results in the synthesis of the BCR-ABL fusion protein, a constitutively active tyrosine kinase (TK). The introduction of imatinib, a TK inhibitor (TKI) specific for BCR-ABL, was a major breakthrough in CML therapy", "CML has enabled the development of Abl-specific tyrosine kinase inhibitors, such as imatinib mesylate", "CML) arises as a consequence of a chromosomal translocation giving rise to the Philadelphia chromosome and Bcr-Abl oncogene.", "CML) is a paradigm for neoplasias that are defined by a unique genetic aberration, the BCR-ABL1 fusion gene", "protein tyrosine kinase inhibitor, imatinib,", "BCR-ABL fusion gene represents the hallmark of chronic myelogenous leukemia (CML) and is derived from a translocation between chromosome 9 and 22.", "CML patients with imatinib treatment", "CML) is characterized by the presence of the Philadelphia chromosome (Ph), a genetic aberration that codes for bcrabl, which plays a key role in disease pathophysiology. The first oral inhibitor of Brc-Abl was imatinib", "CML) is characterized by the presence of the Philadelphia (Ph) chromosome, which results from a reciprocal translocation between the long arms of the chromosomes 9 and 22 t(9;22)(q34;q11). This translocation creates two new genes, BCR-ABL on the 22q- (Ph chromosome) and the reciprocal ABL-BCR on 9q-. ", "tyrosine kinase inhibitor (TKI), introduced into clinical practice in 1998, was imatinib mesylate", "BCR-ABL tyrosine kinase is the critical pathogenetic event in CML and an ideal target for therapy. This was confirmed in clinical trials of imatinib", "CML) is characterized by the presence of a constitutively active Abl kinase, which is the product of a chimeric BCR-ABL gene, caused by the genetic translocation known as the Philadelphia chromosome. Imatinib, a selective inhibitor of the Bcr-Abl tyrosine kinase, ", "CML) is the first human malignancy for which the promise of targeted therapy has come true. CML is invariably associated with a specific genetic lesion--the t(9;22) chromosomal translocation. As a consequence of this translocation, a BCR-ABL fusion gene", "Imatinib mesylate, an orally available tyrosine kinase inhibitor that targets Bcr-Abl,", "CR-ABL tyrosine kinase inhibitors, such as imatinib (Gleevec) are highly effective in treating human Philadelphia chromosome-positive (Ph+) chronic myeloid leukaemia (CML) ", "Chronic myeloid leukemia (CML) is a hematopoietic stem cell cancer driven by the BCR-ABL fusion protein that arises from the translocation of chromosomes 9 and 22", "BCR-ABL inhibitors, such as imatinib", "TKIs (tyrosine kinase inhibitors), including IM (imatinib mesylate),", "chronic myeloid leukaemia) is a myeloproliferative disease that originates in an HSC (haemopoietic stem cell) as a result of the t(9;22) translocation, giving rise to the Ph (Philadelphia chromosome) and bcr-abl oncoprotein", "CML) was the first human malignant disease to be linked to a single, acquired genetic abnormality. Identification of the Bcr-Abl kinase fusion protein and its pivotal role in the pathogenesis of CML provided new opportunities to develop molecular-targeted therapies. Imatinib mesylate", " identification of the Philadelphia chromosome in cells from individuals with chronic myelogenous leukemia (CML) led to the recognition that the BCR-ABL tyrosine kinase causes CML. This in turn led to the development of imatinib mesylate, a clinically successful inhibitor of the BCR-ABL kinase", "CML) was the first human malignancy to be associated with a single genetic abnormality, characterized by a reciprocal translocation involving chromosomes 9 and 22 (the Philadelphia chromosome). The fusion gene that results (BCR-ABL) produces a constitutively activated tyrosine kinase that exists in different isoforms depending on BCR break-points. Imatinib mesylate is a highly selective inhibitor of this kinase,", "CML) is characterized by the presence of the Philadelphia chromosome, which is associated with a balanced translocation involving chromosomes 9 and 22 to produce a fusion gene (bcr-abl) that gives rise to a constitutively activated Abl tyrosine kinase. This kinase led to the discovery of several small-molecule inhibitors, imatinib", "matinib mesylate was designed as an inhibitor targeting the BCR-ABL tyrosine kinase, the molecular counterpart of the Philadelphia translocation t(9;22)(q34;q11).", "CML) is a clonal hematopoietic disorder caused by the reciprocal translocation between chromosome 9 and 22. As a result of this translocation, a novel fusion gene, BCR-ABL, is created on Philadelphia (Ph) chromosome, and the constitutive activity of the BCR-ABL protein tyrosine kinase plays a critical role in the disease pathogenesis. Imatinib mesylate, a selective BCR-ABL tyrosine kinase inhibitor", "CML was the first human cancer demonstrated to be strongly associated to the presence of a recurrent chromosomal translocation (the t(9;22)(q34;q11) that creates the Philadelphia (Ph)-chromosome) and to a specific molecular defect, the formation of a hybrid BCR-ABL gene ", "imatinib, (Glivec, Gleevec, Novartis), a potent tyrosine kinase inhibitor of the Bcr-Abl protein", "matinib mesylate is a new drug that can inhibit the tyrosine kinase activity of Bcr-Abl, the receptors for platelet-derived growth factor receptor(PDGF) and stem cell factor, or c-kit. Chronic myeloid leukemia (CML) is distinguished by the presence of a reciprocal translocation between chromosomes 9 and 22 that results in a shortened chromosome 22, termed the Philadelphia(Ph) chromosome.", "IM) binds to the BCR-ABL protein", "Philadelphia chromosome found in leukemia cells of chronic myelogenous leukemia (CML) patients is produced by translocation between chromosomes 9 and 22, resulting in expression of a chimera protein of Bcr and Abl kinase", "Abl kinase inhibitors were synthesized. STI571 (imatinib mesylate", "CML) is characterized by the Philadelphia translocation that fuses BCR sequences from chromosome 22 upstream of the ABL gene on chromosome 9.", "Imatinib, an ATP-competitive selective inhibitor of Bcr-Abl", "Imatinib mesylate is a tyrosine kinase inhibitor with high affinity for the BCR-ABL fusion protein expressed by the hematopoietic cells in chronic myelogenous leukemia (CML).", "BCR/ABL, encodes an activated tyrosine kinase that can act alone to induce a CML-like syndrome ", "The kinase inhibitor imatinib mesylate (Gleevec)", "hiladelphia chromosome translocation (t(9;22)) results in the molecular juxtaposition of two genes, BCR and ABL, to form an aberrant BCR-ABL gene on chromosome 22. BCR-ABL is critical to the pathogenesis of chronic myelogenous leukemia", "imatinib mesylate (Gleevec,", "matinib mesylate (Glivec) is a selective inhibitor of bcr-abl tyrosine kinase, the product of the Philadelphia chromosome, which is the hallmark of chronic myeloid leukaemia (CML)", "matinib mesylate (STI571, Glivec, Gleevec) is a powerful inhibitor of the tyrosine kinase activity of Bcr-Abl, the oncoprotein responsible for chronic myeloid leukemia (CML)", "CML) is characterized by the presence of a Bcr-Abl fusion protein with deregulated tyrosine kinase activity that is required for maintaining the malignant phenotype. Imatinib, a selective inhibitor of Bcr-Abl", "Imatinib is an orally administered, potent inhibitor of the Bcr-Abl tyrosine kinase.", "Imatinib mesylate (STI571), a selective inhibitor of the Bcr-Abl tyrosine kinase, has significant activity in AP CML.", "Chronic myelogenous leukemia (CML) is characterized by a molecular aberration, a fusion BCR-ABL gene encoding for aberrant tyrosine kinase activity, which is crucial in the pathogenesis of CML. In vitro, inhibition of BCR-ABL protein tyrosine kinase activity by a tyrosine kinase inhibitor, Imatinib mesylate", "CML) is characterised by the occurrence of the Philadelphia (Ph) chromosome (9/22 translocation) and the formation of a fusion protein--the BCR-ABL transcript with constitutive activation of the BCR-ABL tyrosine kinase and consequent changes in the intracellular signal transduction, which is responsible for the deregulated myeloid cell proliferation. STI571 (signal transduction inhibition number 571) is a potent and selective inhibitor of the BCR-ABL tyrosine kinase", "Imatinib mesylate (STI571), a specific Bcr-Abl tyrosine-kinase signal-transduction inhibitor, has shown encouraging activity in phase I and II studies of CML", "Chronic myelogenous leukemia (CML) is caused by the BCR-ABL tyrosine kinase, the product of the Philadelphia chromosome. Imatinib mesylate, formerly STI571, is a selective inhibitor of this kinase.", "CML) is a clonal hematopoietic stem cell disorder characterized by Philadelphia chromosome and resultant production of the constitutively activated BCR-ABL tyrosine kinase. Imatinib (STI571), selective inhibitor of the ABL-tyrosine kinase," ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/16757427", "http://www.ncbi.nlm.nih.gov/pubmed/22037271", "http://www.ncbi.nlm.nih.gov/pubmed/23090888", "http://www.ncbi.nlm.nih.gov/pubmed/22895079", "http://www.ncbi.nlm.nih.gov/pubmed/21279819", "http://www.ncbi.nlm.nih.gov/pubmed/23285088", "http://www.ncbi.nlm.nih.gov/pubmed/22985168", "http://www.ncbi.nlm.nih.gov/pubmed/17379100", "http://www.ncbi.nlm.nih.gov/pubmed/11808344", "http://www.ncbi.nlm.nih.gov/pubmed/19641300", "http://www.ncbi.nlm.nih.gov/pubmed/21672337", "http://www.ncbi.nlm.nih.gov/pubmed/14639002", "http://www.ncbi.nlm.nih.gov/pubmed/12755554", "http://www.ncbi.nlm.nih.gov/pubmed/20875546", "http://www.ncbi.nlm.nih.gov/pubmed/22160058", "http://www.ncbi.nlm.nih.gov/pubmed/16850123", "http://www.ncbi.nlm.nih.gov/pubmed/20425400", "http://www.ncbi.nlm.nih.gov/pubmed/22460758", "http://www.ncbi.nlm.nih.gov/pubmed/21672900", "http://www.ncbi.nlm.nih.gov/pubmed/11870241", "http://www.ncbi.nlm.nih.gov/pubmed/22461032", "http://www.ncbi.nlm.nih.gov/pubmed/12082821", "http://www.ncbi.nlm.nih.gov/pubmed/21892537", "http://www.ncbi.nlm.nih.gov/pubmed/12783369", "http://www.ncbi.nlm.nih.gov/pubmed/21903771", "http://www.ncbi.nlm.nih.gov/pubmed/23174189", "http://www.ncbi.nlm.nih.gov/pubmed/22087818", "http://www.ncbi.nlm.nih.gov/pubmed/22052279", "http://www.ncbi.nlm.nih.gov/pubmed/17382020", "http://www.ncbi.nlm.nih.gov/pubmed/22191306", "http://www.ncbi.nlm.nih.gov/pubmed/22506320", "http://www.ncbi.nlm.nih.gov/pubmed/23942795", "http://www.ncbi.nlm.nih.gov/pubmed/22349810", "http://www.ncbi.nlm.nih.gov/pubmed/19075651", "http://www.ncbi.nlm.nih.gov/pubmed/23666688", "http://www.ncbi.nlm.nih.gov/pubmed/16146726", "http://www.ncbi.nlm.nih.gov/pubmed/17956348", "http://www.ncbi.nlm.nih.gov/pubmed/20425355", "http://www.ncbi.nlm.nih.gov/pubmed/18974832", "http://www.ncbi.nlm.nih.gov/pubmed/15739279", "http://www.ncbi.nlm.nih.gov/pubmed/12869662", "http://www.ncbi.nlm.nih.gov/pubmed/17292736", "http://www.ncbi.nlm.nih.gov/pubmed/16988930", "http://www.ncbi.nlm.nih.gov/pubmed/12411298", "http://www.ncbi.nlm.nih.gov/pubmed/23032801", "http://www.ncbi.nlm.nih.gov/pubmed/21203982", "http://www.ncbi.nlm.nih.gov/pubmed/23233201", "http://www.ncbi.nlm.nih.gov/pubmed/12173333", "http://www.ncbi.nlm.nih.gov/pubmed/17970609", "http://www.ncbi.nlm.nih.gov/pubmed/20529808", "http://www.ncbi.nlm.nih.gov/pubmed/15899391", "http://www.ncbi.nlm.nih.gov/pubmed/15027317", "http://www.ncbi.nlm.nih.gov/pubmed/17364993", "http://www.ncbi.nlm.nih.gov/pubmed/21061842", "http://www.ncbi.nlm.nih.gov/pubmed/19064740", "http://www.ncbi.nlm.nih.gov/pubmed/12176881", "http://www.ncbi.nlm.nih.gov/pubmed/22519766", "http://www.ncbi.nlm.nih.gov/pubmed/12796373", "http://www.ncbi.nlm.nih.gov/pubmed/14744784", "http://www.ncbi.nlm.nih.gov/pubmed/18533795", "http://www.ncbi.nlm.nih.gov/pubmed/22151181", "http://www.ncbi.nlm.nih.gov/pubmed/17382013", "http://www.ncbi.nlm.nih.gov/pubmed/12750692", "http://www.ncbi.nlm.nih.gov/pubmed/17671641", "http://www.ncbi.nlm.nih.gov/pubmed/22761178", "http://www.ncbi.nlm.nih.gov/pubmed/16475128", "http://www.ncbi.nlm.nih.gov/pubmed/12200353", "http://www.ncbi.nlm.nih.gov/pubmed/15791812", "http://www.ncbi.nlm.nih.gov/pubmed/16689455", "http://www.ncbi.nlm.nih.gov/pubmed/18205699", "http://www.ncbi.nlm.nih.gov/pubmed/11986206", "http://www.ncbi.nlm.nih.gov/pubmed/22893108", "http://www.ncbi.nlm.nih.gov/pubmed/16843101", "http://www.ncbi.nlm.nih.gov/pubmed/19860186", "http://www.ncbi.nlm.nih.gov/pubmed/20607973", "http://www.ncbi.nlm.nih.gov/pubmed/19254884", "http://www.ncbi.nlm.nih.gov/pubmed/20945321", "http://www.ncbi.nlm.nih.gov/pubmed/12454739", "http://www.ncbi.nlm.nih.gov/pubmed/17929114" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D010677", "http://www.biosemantics.org/jochem#4275840", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011505", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016044", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D015464", "http://www.disease-ontology.org/api/metadata/DOID:8552" ]

[ "Empagliflozin was approved in 2014 by the European Commission and the United States Food and Drug Administration for the treatment of type 2 diabetes mellitus (T2DM)." ]

[ "2014" ]

[ "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).", "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)", "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)." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/25712444" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D014486", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D017277" ]

[ "Yes, vortioxetine (Lu AA21004) is effective for treatment of major depressive disorder (MDD). Vortioxetine is approved for MDD in the USA. Vortioxetine has been also shown to be effective for treatment of generalized anxiety disorder." ]

[ "yes" ]

[ "Vortioxetine is an orally administered small molecule developed by Lundbeck A/S for the once-daily treatment of major depressive disorder (MDD) and generalized anxiety disorder (GAD). Vortioxetine received its first global approval for MDD in the USA in September 2013 and regulatory approval for its use in this indication in the EU (where it has received a positive opinion) and Canada is awaited. ", "This article summarizes the milestones in the development of vortioxetine leading to this first approval for MDD.", "Vortioxetine was efficacious and well tolerated in the treatment of patients with major depressive disorder.", "On the primary efficacy endpoint, both vortioxetine doses were statistically significantly superior to placebo, with a mean difference to placebo (n=158) of -5.5 (vortioxetine 15 mg, P<0.0001, n=149) and -7.1 MADRS points (vortioxetine 20 mg, P<0.0001, n=151).", "The change in the severity of depressive and anxiety symptoms was maintained throughout the study as reflected by a 24-item Hamilton Depression Scale total score of 8.2 at week 52 (from 17.6 at open-label baseline) in the observed case data set.", "Vortioxetine is a multi-modal antidepressant that functions as a human 5-HT3A and 5-HT7 receptor antagonist, 5-HT1B receptor partial agonist, 5-HT1A receptor agonist, and inhibitor of the serotonin transporter. ", "Approval for the treatment of MDD was based on a clinical development programme that included six positive 6-8 week studies, including one study in elderly people, and one positive maintenance study in adults.", "Vortioxetine represents another option for the treatment of MDD. ", "The multimodal compounds vortioxetine and vilazodone are examples of this approach with diverse mechanisms, and their different clinical effects will provide valuable insights into serotonergic modulation of glutamate transmission for the potential treatment of depression and associated cognitive dysfunction.", "Two new antidepressant drugs, vilazodone (marketed in the USA) and vortioxetine (in development) incorporate partial 5-HT1A-R agonist properties with SERT blockade.", "Novel drugs in development include those that combine multiple simultaneous pharmacologic mechanisms in addition to SERT inhibition within the same molecule, such as vilazodone (combining 5HT1A partial agonism with SERT inhibition), triple reuptake inhibitors (combining norepinephrine and dopamine reuptake inhibition with SERT inhibition), and vortioxetine, a multimodal antidepressant combining actions at the G protein receptor mode (5HT1A and 5HT1B partial agonism and 5HT7 antagonism), at the ion channel mode (5HT3 antagonism) as well as the neurotransmitter transporter mode (SERT inhibition). ", "In this study of adults with MDD treated for 8 weeks with vortioxetine 2.5 mg or 5 mg per day, reductions in depression symptoms were not statistically significant compared with placebo. ", "However, on the basis of these findings, vortioxetine (2.5, 5, 10 mg/day) demonstrated a favourable safety and tolerability profile and maintained effectiveness over 12 months of treatment. ", "In this study of adults with MDD, 5 mg vortioxetine did not differ significantly from placebo in reducing depression symptoms after 6 wk of treatment.", "After 8 weeks of treatment with Lu AA21004 10 mg, there was a significant reduction in HDRS-24 total score compared with placebo in adults with MDD.", "In conclusion, Lu AA21004 was efficacious and well tolerated in the treatment of elderly patients with recurrent major depressive disorder.", "Thus, Lu AA21004 was effective in preventing relapse of MDD and was well tolerated as maintenance treatment.", " Findings on secondary outcome measures, using MMRM instead of LOCF, were supportive of likely efficacy for Lu AA21004 5mg and 10mg and duloxetine. ", "In this study, treatment with 5 mg and 10 mg Lu AA21004 for 6 wk was efficacious and well tolerated in patients with MDD.", "Results from phase II clinical trials have reported improvement in depression and anxiety symptoms after 6 weeks of treatment. " ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/21154150", "http://www.ncbi.nlm.nih.gov/pubmed/21486038", "http://www.ncbi.nlm.nih.gov/pubmed/24284262", "http://www.ncbi.nlm.nih.gov/pubmed/24165478", "http://www.ncbi.nlm.nih.gov/pubmed/22171087", "http://www.ncbi.nlm.nih.gov/pubmed/22495621", "http://www.ncbi.nlm.nih.gov/pubmed/22963932", "http://www.ncbi.nlm.nih.gov/pubmed/24169027", "http://www.ncbi.nlm.nih.gov/pubmed/23252878", "http://www.ncbi.nlm.nih.gov/pubmed/24570588", "http://www.ncbi.nlm.nih.gov/pubmed/24311349", "http://www.ncbi.nlm.nih.gov/pubmed/24016840", "http://www.ncbi.nlm.nih.gov/pubmed/24257717", "http://www.ncbi.nlm.nih.gov/pubmed/23531115", "http://www.ncbi.nlm.nih.gov/pubmed/22978748", "http://www.ncbi.nlm.nih.gov/pubmed/23916504", "http://www.ncbi.nlm.nih.gov/pubmed/21767441", "http://www.ncbi.nlm.nih.gov/pubmed/23757185", "http://www.ncbi.nlm.nih.gov/pubmed/22572889", "http://www.ncbi.nlm.nih.gov/pubmed/22209361", "http://www.ncbi.nlm.nih.gov/pubmed/23903233", "http://www.ncbi.nlm.nih.gov/pubmed/22901346" ]

[]

[ "http://www.disease-ontology.org/api/metadata/DOID:1595", "http://www.disease-ontology.org/api/metadata/DOID:1596", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D003866", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D003865", "http://www.disease-ontology.org/api/metadata/DOID:1470", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D003863", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016896", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013812" ]

[ "Sushi.R is a flexible, quantitative and integrative genomic visualizations for publication-quality multi-panel figures using common genomic data formats including Browser Extensible Data (BED), bedGraph and Browser Extensible Data Paired-End (BEDPE). Sushi.R is open source and made publicly available through GitHub (https://github.com/dphansti/Sushi) and Bioconductor (http://bioconductor.org/packages/release/bioc/html/Sushi.html)." ]

[ "Sushi.R" ]

[ "Sushi.R: flexible, quantitative and integrative genomic visualizations for publication-quality multi-panel figures.", "Interpretation and communication of genomic data require flexible and quantitative tools to analyze and visualize diverse data types, and yet, a comprehensive tool to display all common genomic data types in publication quality figures does not exist to date. To address this shortcoming, we present Sushi.R, an R/Bioconductor package that allows flexible integration of genomic visualizations into highly customizable, publication-ready, multi-panel figures from common genomic data formats including Browser Extensible Data (BED), bedGraph and Browser Extensible Data Paired-End (BEDPE). Sushi.R is open source and made publicly available through GitHub (https://github.com/dphansti/Sushi) and Bioconductor (http://bioconductor.org/packages/release/bioc/html/Sushi.html).", "To address this shortcoming, we present Sushi.R, an R/Bioconductor package that allows flexible integration of genomic visualizations into highly customizable, publication-ready, multi-panel figures from common genomic data formats including Browser Extensible Data (BED), bedGraph and Browser Extensible Data Paired-End (BEDPE)" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/24903420" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016678", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D023281" ]

[ "Classic triad of toxoplasmosis include hydrocephalus, cerebral calcification and chorioretinitis." ]

[ "hydrocephalus", "cerebral calcification", "chorioretinitis" ]

[ "Most patients had systemic manifestations, but only 25% of diagnosed patients exhibited the classic triad of hydrocephalus, cerebral calcification and chorioretinitis.", "The pathogenic potential of T. gondii was recognized in the 1920s and 1930s, in congenitally infected children presenting with the classic triad of symptoms, namely hydrocephalus, retinochoroiditis and encephalitis. ", "Intracranial calcifications within the classical triad were only found in two cases.", "Congenital toxoplasmosis is characterized by the classical triads: hydrocephaly, chorioretinitis and intracerebral calcifications.", "Most patients had systemic manifestations, but only 25% of diagnosed patients exhibited the classic triad of hydrocephalus, cerebral calcification and chorioretinitis. " ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/19744303", "http://www.ncbi.nlm.nih.gov/pubmed/25547178", "http://www.ncbi.nlm.nih.gov/pubmed/7193392", "http://www.ncbi.nlm.nih.gov/pubmed/2089735" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D014125", "http://www.disease-ontology.org/api/metadata/DOID:13336", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012816" ]

[ "Among approximately 70 known imprinted genes are some causing disorders affecting growth, metabolism and cancer predisposition. ", "Approximately 150 imprinted genes are known to date, in humans and mice but, though computational searches have tried to extract intrinsic characteristics of these genes to identify new ones, the existing list is probably far from being comprehensive. To date, fewer than 100 imprinted genes have been identified in the human genome." ]

[ " fewer than 100" ]

[ "Among approximately 70 known imprinted genes are some causing disorders affecting growth, metabolism and cancer predisposition. ", "By applying dsPIG to the mRNA-Seq data, we predicted 94 imprinted genes in 20 cerebellum samples and 57 imprinted genes in 9 diverse tissue samples with expected low false discovery rates. ", "Interestingly, we found that, among biallelically expressed genes, at least 18 genes expressed significantly more transcripts from one allele than the other among different individuals and tissues.", "To date, however, fewer than 100 imprinted genes have been identified in the human genome.", "Approximately 150 imprinted genes are known to date, in humans and mice but, though computational searches have tried to extract intrinsic characteristics of these genes to identify new ones, the existing list is probably far from being comprehensive.", " In this study we analyzed the imprinting of 22 genes in human, mouse, and cattle and found that in only 11 was imprinting conserved across the three species.", "However, 62 unique clones in the library were characterized, all of which were methylated and GC-rich, with a GC content>50%. Of these, 43 clones also showed a CpG(obs)/CpG(exp)>0.6, of which 30 were studied in detail. These unique methylated CpG islands mapped to 23 chromosomal regions, and 12 were differentially methylated regions in uniparental tissues of germline origin, i.e., hydatidiform moles (paternal origin) and complete ovarian teratomas (maternal origin), even though many apparently were methylated in somatic tissues.", "Our findings suggest that there are at most several hundred genes in the human genome that are universally imprinted.", "To date, however, fewer than 100 imprinted genes have been identified in the human genome.", "The Imprinted Gene Catalogue now has more than 200 genes listed, and estimates based on mouse models suggest many more may exist in humans. ", "Our findings suggest that there are at most several hundred genes in the human genome that are universally imprinted. With samples of mRNA from appropriate tissues and a collection of informative cSNPs, a genome-wide search using this methodology could expand the list of genes that undergo genomic imprinting in a tissue- or temporal-specific manner.", "We confirmed that PEG10 is paternally expressed, identified one gene (ZNF331) with multiple lines of data indicating it is imprinted, and predicted several additional imprinting candidate genes. Our findings suggest that there are at most several hundred genes in the human genome that are universally imprinted.", "Our findings suggest that there are at most several hundred genes in the human genome that are universally imprinted." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/22894909", "http://www.ncbi.nlm.nih.gov/pubmed/17955261", "http://www.ncbi.nlm.nih.gov/pubmed/23083219", "http://www.ncbi.nlm.nih.gov/pubmed/24501229", "http://www.ncbi.nlm.nih.gov/pubmed/11932239", "http://www.ncbi.nlm.nih.gov/pubmed/15802919", "http://www.ncbi.nlm.nih.gov/pubmed/17653590" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005796", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016678", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D015894" ]

[ "Exome sequencing is an efficient, sensitive, rapid and relatively cheap method for detection of germline mutations." ]

[ "yes" ]

[ "Whole exome sequencing is an efficient and sensitive method for detection of germline mutations in patients with phaeochromcytomas and paragangliomas", "Whole exome sequencing is sensitive, rapid and efficient for detection of PCC/PGL germline mutations.", "These results from deep sequencing demonstrate a higher mutational detection rate than reported with conventional sequencing methodology.", "We performed exome sequencing of germline DNA from members of the affected family. Exome-wide analysis identified a novel loss-of-function mutation in the BAP1 gene, previously suggested as a tumor suppressor.", "whole-exome sequencing has been widely applied in the identification of germline mutations underlying Mendelian disorders, somatic mutations in various cancers and de novo mutations in neurodevelopmental disorders." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/24102379", "http://www.ncbi.nlm.nih.gov/pubmed/23341325", "http://www.ncbi.nlm.nih.gov/pubmed/23832012", "http://www.ncbi.nlm.nih.gov/pubmed/22468815" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001483", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D018095", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D059472", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009154", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D017421", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D017422", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004252" ]

[ "The pluripotency sustaining factor Nanog, controls a cascade of pathways that are intricately connected to govern pluripotency, self-renewal, genome surveillance and cell fate determination. Elevated expression of Nanog has also been reported to result in clonal expansion of murine ESCs, but it also plays a role in tumor development. A positive regulator of cell proliferation, it is essential for G1 to S transition in human embryonic stem cells while it regulates primordial germ cell migration." ]

[ "cell proliferation", "pluripotency", "cell fate determination", "G1 to S transition", "germ cell migration", "tumour development" ]

[ "critical for the regulation of cancer stem cells.", "the effect of FAK and Nanog cross-regulation on cancer cell morphology, invasion, and growth that plays a significant role in carcinogenesis", "Nanog-like regulates endoderm formation", "In mammalian embryonic stem cells, the acquisition of pluripotency is dependent on Nanog", "we identified a zebrafish Nanog ortholog and found that its knockdown impaired endoderm formation", "establishes a role for Nanog-like in regulating the formation of the extraembryonic tissue required for endoderm induction", "Nanog regulates molecules involved in stemness and cell cycle-signaling pathway for maintenance of pluripotency", "Nanog, a key transcription factor in the maintenance of pluripotency of embryonic stem (ES) and embryonal carcinoma (EC) cells", "Nanog, a positive regulator of ESC proliferation and G1/S transition", "Nanog is a stem cell transcription factor required for self-renewal and for maintaining pluripotency", "NANOG regulates glioma stem cells", "We find that NANOG modulates gliomasphere clonogenicity, CD133(+) stem cell cell behavior and proliferation", "NANOG is essential for GBM tumourigenicity", "Nanog regulates primordial germ cell migration", "Nanog mediates PGC migration by regulating Cxcr4b expression", "Nanog regulates proliferation during early fish development.", "Nanog is necessary for S-phase transition and proliferation in the developing embryo", "our results demonstrate that NANOG, a cell-fate regulatory molecule known to be important for ESC self-renewal, also plays a novel role in tumor development", "the self-renewal gene NANOG regulates human tumor development", "The emerging picture is one in which Oct4 and Nanog control a cascade of pathways that are intricately connected to govern pluripotency, self-renewal, genome surveillance and cell fate determination", "the pluripotency sustaining factor nanog" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/19544407", "http://www.ncbi.nlm.nih.gov/pubmed/20962578", "http://www.ncbi.nlm.nih.gov/pubmed/20581802", "http://www.ncbi.nlm.nih.gov/pubmed/20578184", "http://www.ncbi.nlm.nih.gov/pubmed/22421047", "http://www.ncbi.nlm.nih.gov/pubmed/19139263", "http://www.ncbi.nlm.nih.gov/pubmed/22493428", "http://www.ncbi.nlm.nih.gov/pubmed/22315219", "http://www.ncbi.nlm.nih.gov/pubmed/22378194", "http://www.ncbi.nlm.nih.gov/pubmed/19415763", "http://www.ncbi.nlm.nih.gov/pubmed/16518401", "http://www.ncbi.nlm.nih.gov/pubmed/14728807", "http://www.ncbi.nlm.nih.gov/pubmed/22934707" ]

[]

[ "http://www.uniprot.org/uniprot/NANOG_MOUSE", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0065007" ]

[ "In the rat brain, lamin A and C are expressed in relatively equal amounts, while the expressions of lamin B1 and B2 vary depending on the cell type. Human cells with reduced expression of the major B-type lamin protein, lamin B1, were generated using RNA interference. In addition, horizontal cells and a subpopulation of retinal ganglion cells expressed lamin A and C, while photoreceptor cells expressed neither lamin A nor C, and all other retinal neurons expressed lamin C only. Parallel in vivo experiments showed that treatment with thioglycollate caused the percentage of lamin A/C-positive peritoneal macrophages to increase from 5 to 80% between Days 0 and 6.", "Early embryonic cells and stem cells of mammals generally possess only lamin B while lamins A and C appear later during differentiation. Northern analysis and immunoblotting demonstrated that lamin A/C mRNA and protein were not detectable in some human cell lines whereas lamin B1 was always present. Hemopoietic cells from blood and bone marrow of mammals usually do not express lamins A/C but only lamin B, and this feature distinguishes these cells from the vast majority of somatic cells of the adult animal, which reveal lamins A/C as well as lamin B." ]

[ "late differentiating primary cells" ]

[ "Antibodies specific for mouse A/C lamins, human A/C lamins, or B lamins have been used to define the lamin complement as a function of time in culture and of cell type. ", "dramatic increase in lamin A/C-positive cells was observed in the first 3 days of culture with both accessory cells and macrophages expressing lamins A/C as soon as such cell types could be identified. Parallel in vivo experiments showed that treatment with thioglycollate caused the percentage of lamin A/C-positive peritoneal macrophages to increase from 5 to 80% between Days 0 and 6.", "Early embryonic cells and stem cells of mammals generally possess only lamin B while lamins A and C appear later during differentiation. ", "Northern analysis and immunoblotting demonstrated that lamin A/C mRNA and protein were not detectable in some human cell lines whereas lamin B1 was always present", "In the rat brain, lamin A and C are expressed in relatively equal amounts, while the expressions of lamin B1 and B2 vary depending on the cell type.", "Hemopoietic cells from blood and bone marrow of mammals usually do not express lamins A/C but only lamin B, and this feature distinguishes these cells from the vast majority of somatic cells of the adult animal, which reveal lamins A/C as well as lamin B", "These results demonstrated that EC cells devoid of lamins A and C nevertheless possessed the appropriate mechanisms for the localization and mitotic redistribution of exogenous lamins A and C.", "Spermatogonia and seminoma cells, which follow a differentiation pathway along the spermatogenic lineage and show characteristics of germ cells, do not express A-type lamins.", "While B-type lamins are expressed in almost all cell types, no A-type lamins are present in early vertebrate embryos or undifferentiated embryonal carcinoma cell lines.", "B-type lamins are present in almost all cell types, but A-type lamins are expressed predominantly in differentiated cells, suggesting a role in maintenance of the differentiated state.", "The expression of A-type lamins coincides with cell differentiation and as A-type lamins specifically interact with chromatin, a role in the regulation of differential gene expression has been suggested for A-type lamins.", "In the literature it is conveyed that only B-type lamins are required in these early stages of development and that A-type lamins are not present or required until differentiation of specific cell types associated with specialized tissue is initiated.", "B-type lamins are present in almost all cell types, but A-type lamins are expressed predominantly in differentiated cells, suggesting a role in maintenance of the differentiated state", "The nuclear lamina is a meshwork of intermediate filaments adjacent to the inner nuclear membrane that in mammalian cells is predominantly composed of three proteins: lamin A, lamin B, and lamin C. Because lamin A and C (A-type lamins) expression has been shown to be lacking in several types of undifferentiated or rapidly proliferating cells, we investigated lamin expression in the human liver in conditions with hepatocellular regeneration (cirrhosis of various etiologies and macroregenerative nodules) and in hepatocellular carcinomas of various grades of differentiation", "Our results identify the absence of A-type lamin expression as a novel marker for undifferentiated ES cells and further support a role for nuclear lamins in cell maintenance and differentiation", "In an attempt to provide an additional meaning to lamin-genome contacts, a recent study characterized the association of gene promoters with A-type lamins in progenitor and differentiated cells", "Previous studies have shown that lamin A/C is not expressed during mouse development before day 9, nor in undifferentiated mouse embryonic carcinoma cells. ", "Ectopic expression of an A-type lamin does not interfere with differentiation of lamin A-negative embryonal carcinoma cells.", "Intriguingly, expression of A-type lamins occurs concomitant with cell differentiation and embryonic development. ", "While B-type lamins are expressed in almost all cell types, no A-type lamins are present in early vertebrate embryos or undifferentiated embryonal carcinoma cell lines. Intriguingly, expression of A-type lamins occurs concomitant with cell differentiation and embryonic development.", "B-type lamins are present in almost all cell types, but A-type lamins are expressed predominantly in differentiated cells, suggesting a role in maintenance of the differentiated state. Previous studies have shown that lamin A/C is not expressed during mouse development before day 9, nor in undifferentiated mouse embryonic carcinoma cells.", "On the basis of biochemical properties and sequence criteria, vertebrate lamin proteins are classified as either A- or B-type. While B-type lamins are expressed in almost all cell types, no A-type lamins are present in early vertebrate embryos or undifferentiated embryonal carcinoma cell lines." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/24213377", "http://www.ncbi.nlm.nih.gov/pubmed/21842415", "http://www.ncbi.nlm.nih.gov/pubmed/9363444", "http://www.ncbi.nlm.nih.gov/pubmed/9274531", "http://www.ncbi.nlm.nih.gov/pubmed/20568006", "http://www.ncbi.nlm.nih.gov/pubmed/2404771", "http://www.ncbi.nlm.nih.gov/pubmed/2415378", "http://www.ncbi.nlm.nih.gov/pubmed/7781761", "http://www.ncbi.nlm.nih.gov/pubmed/16179429", "http://www.ncbi.nlm.nih.gov/pubmed/9367621", "http://www.ncbi.nlm.nih.gov/pubmed/8381765", "http://www.ncbi.nlm.nih.gov/pubmed/17203376", "http://www.ncbi.nlm.nih.gov/pubmed/1808207", "http://www.ncbi.nlm.nih.gov/pubmed/2209722", "http://www.ncbi.nlm.nih.gov/pubmed/9410886" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D034882", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D034904", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D002477" ]

[ "There are several definitions of autophagy. Among them, autophagy can be defined as a non- apoptotic programmed cell death that consists on a catabolic trafficking pathway for bulk destruction and turnover of long-lived proteins and organelles via regulated lysosomal degradation." ]

[]

[ "autophagy, a process in which de novo formed membrane enclosed vesicles engulf and consume cellular components", "As a general definition, autophagy encompasses a range of processes in which the cell degrades parts of itself within the lysosome (or the analogous organelle, the vacuole, in yeast and plants), followed by the release and reuse of the breakdown products", "definition of autophagy is the following: all processes in which intracellular material is degraded within the lysosome/vacuole and where the macromolecular constituents are recycled", "Autophagic PCD in animals is defined as being accompanied by an increase in the number of autophagosomes, autolysosomes, and small lytic vacuoles produced by autolysosomes", "utophagy is the endogenous, tightly regulated cellular \"housekeeping\" process responsible for the degradation of damaged and dysfunctional cellular organelles and protein aggregates", "utophagy has been predominantly studied as a nonselective self-digestion process that recycles macromolecules and produces energy in response to starvation", "utophagy is a ubiquitous eukaryotic cytoplasmic quality and quantity control pathway", "utophagy is a catabolic trafficking pathway for bulk destruction and turnover of long-lived proteins and organelles via regulated lysosomal degradation.", " non-apoptotic programmed cell death, such as autophagy ", "utophagy and senescence share a number of characteristics, which suggests that both responses could serve to collaterally protect the cell from the toxicity of external stress such as radiation and chemotherapy and internal forms of stress such as telomere shortening and oncogene activation" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/24308968", "http://www.ncbi.nlm.nih.gov/pubmed/23159909", "http://www.ncbi.nlm.nih.gov/pubmed/20116986", "http://www.ncbi.nlm.nih.gov/pubmed/19323652", "http://www.ncbi.nlm.nih.gov/pubmed/20595626", "http://www.ncbi.nlm.nih.gov/pubmed/23774579", "http://www.ncbi.nlm.nih.gov/pubmed/20404488", "http://www.ncbi.nlm.nih.gov/pubmed/21778180", "http://www.ncbi.nlm.nih.gov/pubmed/23422284", "http://www.ncbi.nlm.nih.gov/pubmed/16271306" ]

[]

[ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0006914", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001343" ]

[ "Bacteria have developed several defense mechanisms against bacteriophages over evolutionary time, but the concept of prokaryotic RNA interference mediated defense mechanism against phages and other invading genetic elements has emerged only recently. Clustered regularly interspaced short palindromic repeats (CRISPR) together with closely associated genes (cas genes) constitute the CASS system that is believed to provide a RNAi-like defense mechanism against bacteriophages within the host bacterium." ]

[ "CRISPR-Cas" ]

[ "he CRISPR-Cas (clustered regularly interspaced short palindromic repeats, CRISPR-associated genes) is an adaptive immunity system in bacteria and archaea that functions via a distinct self-non-self recognition mechanism that is partially analogous to the mechanism of eukaryotic RNA interference (RNAi).", "RNA-guided RNA cleavage by a CRISPR RNA-Cas protein complex.", "Compelling evidence indicates that the CRISPR-Cas system protects prokaryotes from viruses and other potential genome invaders.", "RNA in defense: CRISPRs protect prokaryotes against mobile genetic elements.", "n this article, we discuss our current understanding of this fascinating adaptive and heritable defense system, and describe functional similarities and differences with RNAi in eukaryotes.", "Bacteria have developed several defense mechanisms against bacteriophages over evolutionary time, but the concept of prokaryotic RNA interference mediated defense mechanism against phages and other invading genetic elements has emerged only recently. Clustered regularly interspaced short palindromic repeats (CRISPR) together with closely associated genes (cas genes) constitute the CASS system that is believed to provide a RNAi-like defense mechanism against bacteriophages within the host bacterium.", "In many prokaryotes, noncoding RNAs that arise from the clustered regularly interspaced short palindromic repeat (CRISPR) loci are now thought to mediate defense against viruses and other molecular invaders by an RNAi-like pathway." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/20109154", "http://www.ncbi.nlm.nih.gov/pubmed/16545108", "http://www.ncbi.nlm.nih.gov/pubmed/19706170", "http://www.ncbi.nlm.nih.gov/pubmed/21441598", "http://www.ncbi.nlm.nih.gov/pubmed/17537822", "http://www.ncbi.nlm.nih.gov/pubmed/18971321", "http://www.ncbi.nlm.nih.gov/pubmed/23439366", "http://www.ncbi.nlm.nih.gov/pubmed/19945378" ]

[]

[ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=1900370", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0016246", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=1900368", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011387", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D056890", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005057" ]

[ "The rates of substitution mutations in two directions, v (from an AT-pair to a GC-pair) and u (from a GC-pair to an AT-pair), are usually not the same. Thereafter, the effect of mutation on a genome is not random but has a directionality toward higher or lower GC content of DNA. The net effect, v/(u + v), has previously been defined as directional mutation pressure. Thus, directional mutation pressure (GC/AT pressure) refers to mutational biases between alpha-bases (A or T) and gamma-bases (G or C)." ]

[]

[ "directional mutation pressure for variation of the DNA G + C content due to mutational biases between alpha-bases (A or T) and gamma-bases (G or C)", "A/T-biased directional mutation pressure", "Rates of substitution mutations in two directions, v [from an A-T or T-A nucleotide pair (AT-pair) to a G-C or C-G nucleotide pair (GC-pair)] and u [from a GC-pair to an AT-pair], are usually not the same. The net effect, v/(u + v), has previously been defined as directional mutation pressure (mu D), which explains the wide interspecific variation and narrow intragenomic heterogeneity of DNA G + C content in bacteria.", "The prokaryotic genetic code has been influenced by directional mutation pressure (GC/AT pressure) that has been exerted on the entire genome.", "directional mutation pressure affecting the base composition of DNA, sometimes in the direction of increased GC content and at other times, in the direction of AT.", "GC content of DNA varies, as a result of directional mutation pressure (AT/GC pressure), especially in bacteria.", "the effect of mutation on a genome is not random but has a directionality toward higher or lower guanine-plus-cytosine content of DNA, and this pressure generates directional changes more in neutral parts of the genome than in functionally significant parts.", "GC-biased mutation pressure", "Directional mutation theory predicts that when the mutational bias between A/T and G/C nucleotide pairs is equilibrated with the base composition of a neutral set of DNA nucleotides, the mutation frequency per gene will be much lower than the frequency immediately after the mutator mutation takes place.", "The parity rules lay the foundation for evaluating the biases in synonymous codon usage in terms of (1) directional mutation pressure for variation of the DNA G + C content due to mutational biases between alpha-bases (A or T) and gamma-bases (G or C), (2) strand-bias mutation, for example, by DNA repair during transcription, and (3) functional selection in evolution, for example, due to tRNA abundance.", "Directional mutation theory predicts that when the mutational bias between A/T and G/C nucleotide pairs is equilibrated with the base composition of a neutral set of DNA nucleotides, the mutation frequency per gene will be much lower than the frequency immediately after the mutator mutation takes place.", "Directional mutation pressure, the heterogenicity in the likelihood of different nucleotide substitutions, is used to explain the increasing or decreasing guanine-cytosine content (GC%) in DNA and is represented by microD, in agreement with Sueoka (1962, Proc Natl Acad Sci USA 48:582-592).", "The net effect, v/(u + v), has previously been defined as directional mutation pressure (mu D), which explains the wide interspecific variation and narrow intragenomic heterogeneity of DNA G + C content in bacteria.", "The parity rules lay the foundation for evaluating the biases in synonymous codon usage in terms of (1) directional mutation pressure for variation of the DNA G + C content due to mutational biases between alpha-bases (A or T) and gamma-bases (G or C), (2) strand-bias mutation, for example, by DNA repair during transcription, and (3) functional selection in evolution, for example, due to tRNA abundance.", "The parity rules lay the foundation for evaluating the biases in synonymous codon usage in terms of (1) directional mutation pressure for variation of the DNA G + C content due to mutational biases between alpha-bases (A or T) and gamma-bases (G or C), (2) strand-bias mutation, for example, by DNA repair during transcription, and (3) functional selection in evolution, for example, due to tRNA abundance", "Directional mutation theory predicts that when the mutational bias between A/T and G/C nucleotide pairs is equilibrated with the base composition of a neutral set of DNA nucleotides, the mutation frequency per gene will be much lower than the frequency immediately after the mutator mutation takes place" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/20838599", "http://www.ncbi.nlm.nih.gov/pubmed/3357886", "http://www.ncbi.nlm.nih.gov/pubmed/2326195", "http://www.ncbi.nlm.nih.gov/pubmed/1556753", "http://www.ncbi.nlm.nih.gov/pubmed/2253708", "http://www.ncbi.nlm.nih.gov/pubmed/7932780", "http://www.ncbi.nlm.nih.gov/pubmed/8411203", "http://www.ncbi.nlm.nih.gov/pubmed/7723058", "http://www.ncbi.nlm.nih.gov/pubmed/3454289", "http://www.ncbi.nlm.nih.gov/pubmed/1978331", "http://www.ncbi.nlm.nih.gov/pubmed/8433382" ]

[]

[]

[ "Yes, since the complete genome of yeast is known." ]

[ "yes" ]

[ "or model organisms like yeast, we can now quantify complete proteomes in just a few hours.", "A complete mass-spectrometric map of the yeast proteome applied to quantitative trait analysis.", "So far, attempts to generate such maps for any proteome have failed to reach complete proteome coverage. Here we use a strategy based on high-throughput peptide synthesis and mass spectrometry to generate an almost complete reference map (97% of the genome-predicted proteins) of the Saccharomyces cerevisiae proteome." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/23438854", "http://www.ncbi.nlm.nih.gov/pubmed/12912986", "http://www.ncbi.nlm.nih.gov/pubmed/23334424", "http://www.ncbi.nlm.nih.gov/pubmed/15768030", "http://www.ncbi.nlm.nih.gov/pubmed/14730684", "http://www.ncbi.nlm.nih.gov/pubmed/16784548" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D020543", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D015003" ]

[ "The following mutations of alpha-myosin heavy chain gene are implicated in hypertrophic cardiomyopathy: R403Q; Q1065H and Arg-249-->Gln" ]

[ "R403Q", "Arg403Gln", "Q1065H", "Arg-249-->Gln" ]

[ "Accordingly, pressure overload by transverse aortic constriction (TAC) was induced in 2-month-old, male mice with and without a FHC (R403Q) mutation in α-myosin heavy chain.", "This model (designated TnI-203/MHC-403) was generated by crossbreeding mice with the Gly203Ser cardiac troponin I (TnI-203) and Arg403Gln alpha-myosin heavy chain (MHC-403) FHC-causing mutations. ", "Male but not female mice carrying a single R403Q missense allele for cardiac alpha-myosin heavy chain (M-alphaMHC(R403Q/+) and F-alphaMHC(R403Q/+), respectively) develop significant hypertrophic cardiomyopathy (HCM) compared with male and female wild-type mice (M-alphaMHC(+/+) and F-alphaMHC(+/+), respectively) after approximately 30 wk of age.", "A Q1065H mutation was detected in 1 of 21 HCM probands and was absent in 2 unaffected offspring.", "To understand further the pathogenesis of familial hypertrophic cardiomyopathy, we determined how the cardiomyopathy induced by an Arg403-->Gln missense mutation in the alpha-myosin heavy chain (403) is affected by chronically enhancing sympathetic drive by mating the mice with those overexpressing G(s)alpha (G(s)alpha x403). ", "A mouse model of FHC resulting from a mutation in the alpha-myosin heavy-chain (Arg403Gln) was used to study the electrophysiologic phenotype of this disease.", "We used small-amplitude (0.25%) length-perturbation analysis to examine the mechanical properties of skinned left ventricular papillary muscle strips from mouse hearts bearing the R403Q mutation in the alpha-myosin heavy chain (alphaMHC403/+).", "Genetically-manipulated mice harboring an alpha-myosin heavy chain Arg403Gln missense mutation (alpha-MHC403/+) display a phenotype characteristic of familial hypertrophic cardiomyopathy (FHC).", "A new mouse cardiac electrophysiology method was used to study mice harboring an alpha-myosin heavy chain Arg403Gln missense mutation (alpha-MHC403/+), which results in histological and hemodynamic abnormalities characteristic of familial hypertrophic cardiomyopathy (FHC) and sudden death of uncertain etiology during exercise. ", "The introduction of the mouse model for FHC (the mouse expresses predominantly alpha-MHC as opposed to the beta-isoform in larger mammals) created a new paradigm for FHC based on finding enhanced motor function for R403Q alpha-MHC.", "A mouse model of familial hypertrophic cardiomyopathy (FHC) was generated by the introduction of an Arg 403 --> Gln mutation into the alpha cardiac myosin heavy chain (MHC) gene.", "Biochemical analysis of one FHC mutant (Arg-249-->Gln) demonstrates that the structures formed by the mutant are solubilized at a lower ionic strength than those formed by wild-type MHC. We conclude that although the FHC mutant MHC is not labile, its assembly properties may be impaired." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/11827928", "http://www.ncbi.nlm.nih.gov/pubmed/18480046", "http://www.ncbi.nlm.nih.gov/pubmed/8290568", "http://www.ncbi.nlm.nih.gov/pubmed/9884344", "http://www.ncbi.nlm.nih.gov/pubmed/8614836", "http://www.ncbi.nlm.nih.gov/pubmed/9869991", "http://www.ncbi.nlm.nih.gov/pubmed/15998695", "http://www.ncbi.nlm.nih.gov/pubmed/10066683", "http://www.ncbi.nlm.nih.gov/pubmed/9045856", "http://www.ncbi.nlm.nih.gov/pubmed/23986715", "http://www.ncbi.nlm.nih.gov/pubmed/18362229", "http://www.ncbi.nlm.nih.gov/pubmed/10231857", "http://www.ncbi.nlm.nih.gov/pubmed/18281382" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D002312", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D018995" ]

[ "Cardiac manifestations of Marfan syndrome include aortic root dilation,aortic regurgitation, mitral valve prolapse and mitral valve regurgitation." ]

[ "aortic root dilation", "mitral valve prolapse", "aortic regurgitation", "mitral valve regurgitation" ]

[ "Cardiac manifestations of Marfan syndrome include aortic root dilation and mitral valve prolapse (MVP).", "Marfan syndrome (MFS) is a genetic disorder of the connective tissue. Aortic root dilation is a main criterion of the Ghent Nosology. Dural ectasia and the presence of mitral valve prolapse (MVP) contribute to its systemic score.", "The typical cardiac manifestations of Marfan syndrome are aortic regurgitation with progressive dilatation of the aortic root, which may cause dissection and rupture of the ascending aorta, mitral valve prolapse and mitral valve regurgitation.", "To describe the clinical cardiac manifestations and temporal evolution of Marfan syndrome in children; to estimate the incidence of annuloaortic ectasia and mitral valve prolapse", "the presence of mitral valve prolapse, aortic root diameter, mitral and aortic valves regurgitation, and aortic enlargement during beta-blocker therapy", "Cardiovascular manifestations in Marfan syndrome.", "The major cardiac diagnoses were aortic dilatation (1/3) and mitral valve prolapse with severe mitral regurgitation (2/3).", "Marfan syndrome is a hereditable disorder of connective tissue that causes several distinct cardiovascular abnormalities, including aortic regurgitation, dissection, and aneurysm." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/21866385", "http://www.ncbi.nlm.nih.gov/pubmed/2225986", "http://www.ncbi.nlm.nih.gov/pubmed/16358146", "http://www.ncbi.nlm.nih.gov/pubmed/22457261", "http://www.ncbi.nlm.nih.gov/pubmed/11865681", "http://www.ncbi.nlm.nih.gov/pubmed/7113187", "http://www.ncbi.nlm.nih.gov/pubmed/20301510", "http://www.ncbi.nlm.nih.gov/pubmed/15755703", "http://www.ncbi.nlm.nih.gov/pubmed/24043612", "http://www.ncbi.nlm.nih.gov/pubmed/15554020", "http://www.ncbi.nlm.nih.gov/pubmed/21161115", "http://www.ncbi.nlm.nih.gov/pubmed/8322324", "http://www.ncbi.nlm.nih.gov/pubmed/22397493", "http://www.ncbi.nlm.nih.gov/pubmed/9586150", "http://www.ncbi.nlm.nih.gov/pubmed/20232788", "http://www.ncbi.nlm.nih.gov/pubmed/9587454", "http://www.ncbi.nlm.nih.gov/pubmed/24030414", "http://www.ncbi.nlm.nih.gov/pubmed/11159287" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D008382" ]

[ "Mutations in cardiac beta-myosin heavy chain and alpha-tropomyosin link isolated Non-compaction cardiomyopathy with dilated cardiomyopathy" ]

[ "via mutations in beta-MHC and alpha-TPM1" ]

[ "A novel alpha-tropomyosin mutation associates with dilated and non-compaction cardiomyopathy and diminishes actin binding", "We show that a mutation in TPM1 is associated with DCM and a lethal, early onset form of NCCM, probably as a result of diminished actin binding caused by weakened charge-charge interactions.", "We describe, in two separate autosomal-dominant NCCM families, the identification of mutations in the sarcomeric cardiac beta-myosin heavy chain gene (MYH7), known to be associated with hypertrophic cardiomyopathy (HCM), restricted cardiomyopathy (RCM), and dilated cardiomyopathy (DCM).", "These results confirm the genetic heterogeneity of NCCM and suggest that the molecular classification of cardiomyopathies includes an MYH7-associated spectrum of NCCM with HCM, RCM, and DCM." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/23147248", "http://www.ncbi.nlm.nih.gov/pubmed/17947214" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D002311", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D056830" ]

[ "AMPK activation protects cardiac structure and function by increasing cardiac autophagy in the diabetic heart. Decreased AMPK activity and the subsequent reduction in cardiac autophagy are central to the development of diabetic cardiomyopathy. In fact, dissociation of Bcl-2 from Beclin1 may be an important mechanism for preventing diabetic cardiomyopathy via AMPK activation that restores autophagy and protects against cardiac apoptosis. In addition, genetic inhibition of AMPK in cardiomyocytes attenuates cardiac autophagy, exacerbates cardiac dysfunction and increases mortality in diabetic mice. The modulation of AT-1R/AMPK-MAPK pathway might play crucial roles for the pathogenesis of diabetic cardiomyopathy and it could become an important therapeutic target to ameliorate the diabetic cardiomyopathy. Stimulation of AMPK by metformin or trimetazidine administration may represent a novel approach to treat diabetic cardiomyopathy." ]

[]

[ "We recently reported that diabetes depresses AMP-activated protein kinase (AMPK) activity, inhibits MAPK8/JNK1-BCL2 signaling", "Activation of AMPK directly phosphorylates MAPK8, which mediates BCL2 phosphorylation and subsequent BECN1-BCL2 dissociation, leading to restoration of cardiac autophagy, protection against cardiac apoptosis, and ultimately improvement in cardiac structure and function.", "studies were shown that p38 MAPK stimulates glucose uptake through the AMPK activation.", "Taken together, it is suggested that the modulation of AT-1R/AMPK-MAPK pathway might play crucial roles for the pathogenesis of diabetic cardiomyopathy and it could become an important therapeutic target to ameliorate the diabetic cardiomyopathy.", "We conclude that AMPK activation protects cardiac structure and function by increasing cardiac autophagy in the diabetic heart.", "Genetic inhibition of AMPK in cardiomyocytes attenuates cardiac autophagy, exacerbates cardiac dysfunction and increases mortality in diabetic mice.", "Oxidative stress and lipid deposition were markedly increased in the myocardium, concomitant with inactivation of AMPK and increased expression of peroxisome proliferator-activated receptor coactivator-1 alpha (PGC-1 alpha).", "Trimetazidine also caused AMPK activation and reduced PGC-1 alpha expression in the hearts of db/db mice.", "The data suggest that trimetazidine significantly improves cardiac function in db/db mice by attenuating lipotoxicity and improving the oxidation status of the heart. Activation of AMPK and decreased expression of PGC-1 alpha were involved in this process.", "Our findings highlight a role of PP2C and AMPK in the derangements of cardiac lipid metabolism in obesity and provide new insights as to the mechanisms of the liporegulatory disorder leading to lipotoxic cardiomyopathy.", "We conclude that dissociation of BCL2 from BECN1 through activation of MAPK8-BCL2 signaling may be an important mechanism by which AMPK activation restores autophagy, protects against cardiac apoptosis, and prevents diabetic cardiomyopathy.", "Both the AMPK activator resveratrol and the antioxidant N-acetylcysteine mimicked the UCF-101-induced beneficial effect in STZ-induced diabetic cardiomyocytes.", "UCF-101 protects against STZ-induced cardiomyocyte contractile dysfunction, possibly via an AMPK-associated mechanism." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/23223177", "http://www.ncbi.nlm.nih.gov/pubmed/19561140", "http://www.ncbi.nlm.nih.gov/pubmed/22842069", "http://www.ncbi.nlm.nih.gov/pubmed/22146585", "http://www.ncbi.nlm.nih.gov/pubmed/20383170", "http://www.ncbi.nlm.nih.gov/pubmed/21562078", "http://www.ncbi.nlm.nih.gov/pubmed/23380689", "http://www.ncbi.nlm.nih.gov/pubmed/21685727", "http://www.ncbi.nlm.nih.gov/pubmed/15367397" ]

[]

[ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0004679", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0031588", "http://www.uniprot.org/uniprot/AAPK2_RAT", "http://www.uniprot.org/uniprot/AAKG2_HUMAN", "http://www.uniprot.org/uniprot/AAKB2_RAT", "http://www.uniprot.org/uniprot/AAKG1_HUMAN", "http://www.uniprot.org/uniprot/AAPK2_HUMAN", "http://www.uniprot.org/uniprot/AAPK1_CAEEL", "http://www.uniprot.org/uniprot/AAPK1_PIG", "http://www.uniprot.org/uniprot/AAPK2_PONAB", "http://www.uniprot.org/uniprot/AAKG1_BOVIN", "http://www.uniprot.org/uniprot/AAKB1_PIG", "http://www.uniprot.org/uniprot/AAPK1_MOUSE", "http://www.uniprot.org/uniprot/AAPK1_RAT", "http://www.uniprot.org/uniprot/AAKB1_BOVIN", "http://www.uniprot.org/uniprot/AAKG2_MOUSE", "http://www.uniprot.org/uniprot/AAKG1_RAT", "http://www.uniprot.org/uniprot/AAKB1_HUMAN", "http://www.uniprot.org/uniprot/AAPK1_PONAB", "http://www.uniprot.org/uniprot/AAKG1_MOUSE", "http://www.disease-ontology.org/api/metadata/DOID:9351", "http://www.uniprot.org/uniprot/AAKG2_PONAB", "http://www.uniprot.org/uniprot/AAKB2_HUMAN", "http://www.uniprot.org/uniprot/AAKG1_PIG", "http://www.uniprot.org/uniprot/AAKB1_MOUSE", "http://www.uniprot.org/uniprot/AAKB1_PONAB", "http://www.uniprot.org/uniprot/AAPK2_MOUSE", "http://www.uniprot.org/uniprot/AAPK2_CAEEL", "http://www.uniprot.org/uniprot/AAPK1_HUMAN", "http://www.uniprot.org/uniprot/AAKG_YEAST", "http://www.uniprot.org/uniprot/AAKB2_MOUSE", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D058065", "http://www.uniprot.org/uniprot/AAKB1_RAT", "http://www.uniprot.org/uniprot/AAPK2_PIG" ]

[ "Yes. Circular RNAs (circRNAs) play a crucial role in fine tuning the level of miRNA mediated regulation of gene expression by sequestering the miRNAs. Their interaction with disease associated miRNAs indicates that circular RNAs are important for disease regulation." ]

[ "yes" ]

[ "Circ2Traits: a comprehensive database for circular RNA potentially associated with disease and traits.", "Circular RNAs play a crucial role in fine tuning the level of miRNA mediated regulation of gene expression by sequestering the miRNAs. Their interaction with disease associated miRNAs indicates that circular RNAs are important for disease regulation.", "Firstly, the interactions of circRNAs with disease associated miRNAs were identified, following which the likelihood of a circRNA being associated with a disease was calculated", "Emerging evidence indicates that circRNAs might play important roles in atherosclerotic vascular disease risk, neurological disorders, prion diseases and cancer; exhibit aberrant expression in colorectal cancer (CRC) and pancreatic ductal adenocarcinoma (PDAC); and serve as diagnostic or predictive biomarkers of some diseases", "In this paper we studied the potential association of circular RNAs (circRNA) with human diseases in two different ways. Firstly, the interactions of circRNAs with disease associated miRNAs were identified, following which the likelihood of a circRNA being associated with a disease was calculated.", "Firstly, the interactions of circRNAs with disease associated miRNAs were identified, following which the likelihood of a circRNA being associated with a disease was calculated. For the miRNAs associated with individual diseases, we constructed a network of predicted interactions between the miRNAs and protein coding, long non-coding and circular RNA genes." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/26052092", "http://www.ncbi.nlm.nih.gov/pubmed/24339831" ]

[]

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

[ "the most common cause of sudden cardiac death in young athletes is hypertrophic cardiomyopathy" ]

[ "hypertrophic cardiomyopathy" ]

[ "The most common cause of death was hypertrophic cardiomyopathy (30 %), followed by coronary artery anomalies (9 %), and myocarditis (9 %). ", "The most common cause of this, hypertrophic cardiomyopathy (HCM), is a genetic disorder responsible for more than a third of cases and is manageable.", "HCM is the most common cause of sudden death in young competitive athletes and preparticipation screening programs have to be implemented to avoid these tragic fatalities. ", "Hypertrophic cardiomyopathy (HCM) is the most common cause of sudden cardiac death (SCD) in young people, including trained athletes.", "Hypertrophic cardiomyopathy (HCM) is regarded as the most common cause of sudden cardiac death in young people (including trained athletes). ", "Hypertrophic cardiomyopathy (HCM) is the most common cause of sudden cardiac death in young people, including trained athletes. ", "Hypertrophic cardiomyopathy is regarded as the most common cause of sudden cardiac death in young people (including trained athletes).", "The most common cause of sudden cardiac death in athletes is hypertrophic cardiomyopathy. ", "Hypertrophic cardiomyopathy (HCM) is one of the most common inherited primary cardiac disorders and the most common cause of sudden cardiac death in young athletes.", "The most common cause of sudden cardiac death in individuals aged less than 35 years, including competitive athletes, is the inherited disorder hypertrophic cardiomyopathy (HCM). ", "udden death in young competitive athletes is due to a variety of cardiovascular diseases (CVDs) and, most commonly, HCM. ", "Hypertrophic cardiomyopathy (HCM) is the most common cause of death in the young, particularly in young competitive athletes.", "Hypertrophic cardiomyopathy (HC) is probably the most common cause of sudden cardiac death in youthful athletes, and this diagnosis has represented a contraindication to continued participation in competitive sports. " ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/16352133", "http://www.ncbi.nlm.nih.gov/pubmed/21858983", "http://www.ncbi.nlm.nih.gov/pubmed/11886323", "http://www.ncbi.nlm.nih.gov/pubmed/12793636", "http://www.ncbi.nlm.nih.gov/pubmed/12651044", "http://www.ncbi.nlm.nih.gov/pubmed/20559995", "http://www.ncbi.nlm.nih.gov/pubmed/6686529", "http://www.ncbi.nlm.nih.gov/pubmed/20962423", "http://www.ncbi.nlm.nih.gov/pubmed/7788945", "http://www.ncbi.nlm.nih.gov/pubmed/10798028", "http://www.ncbi.nlm.nih.gov/pubmed/21716109", "http://www.ncbi.nlm.nih.gov/pubmed/18325444", "http://www.ncbi.nlm.nih.gov/pubmed/19336382", "http://www.ncbi.nlm.nih.gov/pubmed/22846097", "http://www.ncbi.nlm.nih.gov/pubmed/15929462", "http://www.ncbi.nlm.nih.gov/pubmed/20378375", "http://www.ncbi.nlm.nih.gov/pubmed/21234187", "http://www.ncbi.nlm.nih.gov/pubmed/6446987", "http://www.ncbi.nlm.nih.gov/pubmed/1554567", "http://www.ncbi.nlm.nih.gov/pubmed/22874472", "http://www.ncbi.nlm.nih.gov/pubmed/8667563", "http://www.ncbi.nlm.nih.gov/pubmed/17157688", "http://www.ncbi.nlm.nih.gov/pubmed/21160605", "http://www.ncbi.nlm.nih.gov/pubmed/19575162", "http://www.ncbi.nlm.nih.gov/pubmed/9858396", "http://www.ncbi.nlm.nih.gov/pubmed/9636339", "http://www.ncbi.nlm.nih.gov/pubmed/17853713", "http://www.ncbi.nlm.nih.gov/pubmed/8198037", "http://www.ncbi.nlm.nih.gov/pubmed/17322504", "http://www.ncbi.nlm.nih.gov/pubmed/17961794", "http://www.ncbi.nlm.nih.gov/pubmed/18384577", "http://www.ncbi.nlm.nih.gov/pubmed/11043079", "http://www.ncbi.nlm.nih.gov/pubmed/1450882", "http://www.ncbi.nlm.nih.gov/pubmed/23681420" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016757", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D056352", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D002423" ]

[ "Yes. The view of Menzerath-Altmann law in genomes, as inevitable, is seriously flawed." ]

[ "yes" ]

[ "Here we review the statistical foundations of that test and consider three non-parametric tests based upon different correlation metrics and one parametric test to evaluate if Z ∼ 1/X in genomes. The most powerful test is a new non-parametric one based upon the correlation ratio, which is able to reject Z ∼ 1/X in nine out of 11 taxonomic groups and detect a borderline group. Rather than a fact, Z ∼ 1/X is a baseline that real genomes do not meet. The view of Menzerath-Altmann law as inevitable is seriously flawed.", "The view of Menzerath-Altmann law as inevitable is seriously flawed.", "The view of Menzerath-Altmann law as inevitable is seriously flawed.", "The view of Menzerath-Altmann law as inevitable is seriously flawed." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/25503672" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016678" ]

[ "Survival rates for commotio cordis are low, even when resuscitation is performed. Survival rates vary between 10% and 28%." ]

[ "10-28%" ]

[ "At their commotio cordis event, 216 study patients were 0.2-51 years old (mean age 15±9 years); 95% were males. Death occurred in 156 individuals (72%), while the other 60 (28%) survived.", "In the 2 groups, events were largely similar demographically, including frequency of survival (26% in U.S. vs 25%; P = .84),", "Survival of commotio cordis has risen from 10% to 15% since 2001.", "Only 21 (16%) individuals survived their event, with particularly prompt cardiopulmonary resuscitation/defibrillation (most commonly reversing ventricular fibrillation) the only identifiable factor associated with a favorable outcome.", "Survival rates for commotio cordis are low, even with prompt CPR and defibrillation.", "Survival is low, even when resuscitation is performed. " ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/23107651", "http://www.ncbi.nlm.nih.gov/pubmed/23015869", "http://www.ncbi.nlm.nih.gov/pubmed/11879111", "http://www.ncbi.nlm.nih.gov/pubmed/11555799", "http://www.ncbi.nlm.nih.gov/pubmed/21763255", "http://www.ncbi.nlm.nih.gov/pubmed/20086611" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013534", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D056104" ]

[ "The Tyrolean Iceman's brain is the oldest (5300 years old) human sample that has been studied by paleoproteomics." ]

[]

[ "Paleoproteomic study of the Iceman's brain tissue.", "We report the first use of shotgun proteomics to detect the protein expression profile of buccal swabs and cloth samples from two 500-year-old Andean mummies.", "Identification of ancient biological samples from the 1991-discovered and more than 5300-year-old Tyrolean mummy, also called iceman or Oetzi, is very difficult. T", "To determine whether a 2,700-year-old tumor can be reliably diagnosed using microscopic and proteomic techniques " ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/22348088", "http://www.ncbi.nlm.nih.gov/pubmed/18720427", "http://www.ncbi.nlm.nih.gov/pubmed/23739949", "http://www.ncbi.nlm.nih.gov/pubmed/22848450", "http://www.ncbi.nlm.nih.gov/pubmed/17918181" ]

[ { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A0096938", "o": "MeSH" }, { "p": "http://linkedlifedata.com/resource/umls/prefMetaMap", "s": "http://linkedlifedata.com/resource/umls/id/C0030224", "o": "http://linkedlifedata.com/resource/umls/label/A0096938" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C0030224", "o": "http://linkedlifedata.com/resource/umls/label/A1308492" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A1308492", "o": "paleontology" }, { "p": "http://linkedlifedata.com/resource/umls/altMetaMap", "s": "http://linkedlifedata.com/resource/umls/id/C0030224", "o": "http://linkedlifedata.com/resource/umls/label/A0096937" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A0096937", "o": "Paleontology" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A0096938", "o": "D010163" } ]

[ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D020543", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D010163", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D006801", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D040901" ]

[ "Loss of Lon1 in Arabidopsis changes the mitochondrial proteome leading to altered metabolite profiles and growth retardation. Additionaly, seedling establishment is also impaired." ]

[ "growth rate deficit in both roots and shoots", "lowered activity of specific mitochondrial enzymes associated with respiratory metabolism", "impaired seedling establishment" ]

[ "Knockout in Arabidopsis (Arabidopsis thaliana) leads to a significant growth rate deficit in both roots and shoots and lowered activity of specific mitochondrial enzymes associated with respiratory metabolism. ", "loss of Lon1 significantly modifies respiratory function and plant performance by small but broad alterations in the mitochondrial proteome gained by subtly changing steady-state protein assembly, stability, and damage of a range of components that debilitate an anaplerotic role for mitochondria in cellular carbon metabolism.", "the lack of Lon selective proteolysis leading to growth retardation and impaired seedling establishment can be attributed to defects in the oil reserve mobilization pathway. ", "Loss of Lon1 in Arabidopsis changes the mitochondrial proteome leading to altered metabolite profiles and growth retardation without an accumulation of oxidative damage.", " a genetic screen was performed that led to the identification of Arabidopsis thaliana Lon1 protease mutants that exhibit a post-embryonic growth retardation phenotype.", "mitochondria isolated from lon1 mutants had a lower capacity for respiration of succinate and cytochrome c via complexes II and IV, respectively. Furthermore, the activity of key enzymes of the tricarboxylic acid (TCA) cycle was significantly reduced. Additionally, mitochondria in lon1 mutants had an aberrant morphology. ", " AtLon1 protease in organelle biogenesis and seedling establishment." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/19076295", "http://www.ncbi.nlm.nih.gov/pubmed/22968828", "http://www.ncbi.nlm.nih.gov/pubmed/22023720" ]

[]

[ "http://www.uniprot.org/uniprot/LON_AQUAE", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D017360", "http://www.uniprot.org/uniprot/LON_MYCAP", "http://www.uniprot.org/uniprot/LON_DESDA", "http://www.uniprot.org/uniprot/LON_BUCAP", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D029681", "http://www.uniprot.org/uniprot/LON_RICFE", "http://www.uniprot.org/uniprot/LON_ORITI", "http://www.uniprot.org/uniprot/LON_CHLT3", "http://www.uniprot.org/uniprot/LON_GEOMG", "http://www.uniprot.org/uniprot/LON_ERWAM", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D049070" ]

[ "Giant axonal neuropathy (GAN) is a progressive neurodegenerative disease caused by autosomal recessive mutations in the GAN gene resulting in a loss of a ubiquitously expressed protein, gigaxonin", "Giant axonal neuropathy (GAN) is a progressive neurodegenerative disease caused by autosomal recessive mutations in the GAN gene, resulting in a loss of a ubiquitously expressed protein, gigaxonin." ]

[ "GAN gene" ]

[ "Giant axonal neuropathy (GAN) is a progressive neurodegenerative disease caused by autosomal recessive mutations in the GAN gene resulting in a loss of a ubiquitously expressed protein, gigaxonin", "We describe a toddler with clinical features suggesting giant axonal neuropathy (GAN), whose diagnosis was confirmed by minimally invasive skin biopsy and corroborated by the finding of compound heterozygous mutations involving the GAN gene", "Giant Axonal Neuropathy is a pediatric neurodegenerative disorder caused by autosomal recessive mutations in the GAN gene on chromosome 16q24.1", "Giant axonal neuropathy (GAN) is a rare autosomal recessive neurodegenerative disorder caused by mutations in the GAN gene", "Giant axonal neuropathy (GAN) is a rare pediatric neurodegenerative disease. It is best known for the \"giant\" axons caused by accumulations of intermediate filaments. The disease is progressive, with onset around age 3 years and death by the third decade of life. GAN results from recessive mutations in the GAN gene encoding gigaxonin", "Restoration of cytoskeleton homeostasis after gigaxonin gene transfer for giant axonal neuropathy.", "A novel mutation in the GAN gene causes an intermediate form of giant axonal neuropathy in an Arab-Israeli family.", "In this family, missense mutation of c.224 T>A and missense mutation of c.1634G>A in GAN gene caused the phenotype of giant axonal neuropathy in the proband.", "Different missense, nonsense and frameshift mutations in the GAN gene encoding gigaxonin have been described to cause giant axonal neuropathy, a severe early-onset progressive neurological disease with autosomal recessive inheritance.", "The giant axonal neuropathy gene was localised by homozygosity mapping to chromosome 16q24.1 and identified as encoding a novel, ubiquitously expressed cytoskeletal protein named gigaxonin.We describe a consanguineous Algerian family with three affected sibs aged 16, 14 and 12 years who present a mild demyelinating sensory motor neuropathy, hypoacousia and kyphoscoliosis which was moderate in the two elder patients, severe in the third one, with no sign of central nervous system involvement and normal cerebral magnetic resonance imaging.", "Giant axonal neuropathy (GAN): case report and two novel mutations in the gigaxonin gene.", "Giant axonal neuropathy caused by a novel compound heterozygous mutation in the gigaxonin gene.", "Giant axonal neuropathy (GAN) is a rare autosomal recessive neurodegenerative disorder caused by mutations in the GAN gene", "Giant axonal neuropathy caused by a novel compound heterozygous mutation in the gigaxonin gene", "We describe a toddler with clinical features suggesting giant axonal neuropathy (GAN), whose diagnosis was confirmed by minimally invasive skin biopsy and corroborated by the finding of compound heterozygous mutations involving the GAN gene, including a novel interstitial microdeletion at 16q23.2 detected by microarray and a point mutation detected by direct sequencing", "Indeed, recessive mutations in the Gigaxonin-encoding gene cause Giant Axonal Neuropathy (GAN), a severe neurodegenerative disorder characterized by a wide disorganization of the Intermediate Filament network", "A novel mutation in the GAN gene causes an intermediate form of giant axonal neuropathy in an Arab-Israeli family", "Restoration of cytoskeleton homeostasis after gigaxonin gene transfer for giant axonal neuropathy", "Giant axonal neuropathy (GAN)(1) is a rare autosomal recessive neurological disorder caused by mutations in the GAN gene that encodes gigaxonin, a member of the BTB/Kelch family of E3 ligase adaptor proteins.(1) This disease is characterized by the aggregation of Intermediate Filaments (IF)-cytoskeletal elements that play important roles in cell physiology including the regulation of cell shape, motility, mechanics and intra-cellular signaling", "Giant Axonal Neuropathy is a pediatric neurodegenerative disorder caused by autosomal recessive mutations in the GAN gene on chromosome 16q24.1. ", "Indeed, recessive mutations in the Gigaxonin-encoding gene cause Giant Axonal Neuropathy (GAN), a severe neurodegenerative disorder characterized by a wide disorganization of the Intermediate Filament network. ", "The instability of the BTB-KELCH protein Gigaxonin causes Giant Axonal Neuropathy and constitutes a new penetrant and specific diagnostic test.", "We describe a toddler with clinical features suggesting giant axonal neuropathy (GAN), whose diagnosis was confirmed by minimally invasive skin biopsy and corroborated by the finding of compound heterozygous mutations involving the GAN gene, including a novel interstitial microdeletion at 16q23.2 detected by microarray and a point mutation detected by direct sequencing.", "INTRODUCTION: Giant axonal neuropathy (GAN) is a rare autosomal recessive neurodegenerative disorder caused by mutations in the GAN gene. ", "Analysis of the microarray data identified a change in the gene giant axonal neuropathy 1 (Gan1). Mutation of this gene has been linked to the development of giant axonal neuropathy (GAN), a rare autosomal recessive condition characterized by a progressive sensorimotor neuropathy.", " Giant axonal neuropathy (GAN, MIM: 256850) is a devastating autosomal recessive disorder characterized by an early onset severe peripheral neuropathy, varying central nervous system involvement and strikingly frizzly hair. Giant axonal neuropathy is usually caused by mutations in the gigaxonin gene (GAN) but genetic heterogeneity has been demonstrated for a milder variant of this disease.", "Giant axonal neuropathy caused by a novel compound heterozygous mutation in the gigaxonin gene.", "A novel mutation in the GAN gene causes an intermediate form of giant axonal neuropathy in an Arab-Israeli family.", "Giant Axonal Neuropathy is a pediatric neurodegenerative disorder caused by autosomal recessive mutations in the GAN gene on chromosome 16q24.1.", "Restoration of cytoskeleton homeostasis after gigaxonin gene transfer for giant axonal neuropathy.", "Giant axonal neuropathy (GAN) is a rare autosomal recessive neurodegenerative disorder caused by mutations in the GAN gene." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/23248352", "http://www.ncbi.nlm.nih.gov/pubmed/25003002", "http://www.ncbi.nlm.nih.gov/pubmed/11971098", "http://www.ncbi.nlm.nih.gov/pubmed/19398414", "http://www.ncbi.nlm.nih.gov/pubmed/23890932", "http://www.ncbi.nlm.nih.gov/pubmed/24947478", "http://www.ncbi.nlm.nih.gov/pubmed/24273072", "http://www.ncbi.nlm.nih.gov/pubmed/17587580", "http://www.ncbi.nlm.nih.gov/pubmed/12398836", "http://www.ncbi.nlm.nih.gov/pubmed/23332420", "http://www.ncbi.nlm.nih.gov/pubmed/24758703", "http://www.ncbi.nlm.nih.gov/pubmed/23316953", "http://www.ncbi.nlm.nih.gov/pubmed/25398950", "http://www.ncbi.nlm.nih.gov/pubmed/20949505", "http://www.ncbi.nlm.nih.gov/pubmed/19295179", "http://www.ncbi.nlm.nih.gov/pubmed/24211141" ]

[]

[]

[ "The Notch signaling pathway is an evolutionarily conserved, intercellular signaling mechanism essential for proper embryonic development in organisms as diverse as insects, nematodes, echinoderms and mammals. Disruptions in conserved developmental pathways frequently result in inherited congenital anomalies in humans. Mutations in genes encoding Notch pathway components underlie human disease such as Down syndrome, Pick's and Prion's disease, and cadasil syndrome." ]

[ "yes" ]

[ "he Notch signaling pathway plays a critical role in maintaining the balance between cell proliferation, differentiation and apoptosis, and is a highly conserved signaling pathway that regulates normal development in a context- and dose-dependent manner. Dysregulation of Notch signaling has been suggested to be key events in a variety of hematological malignancies. Notch1 signaling appears to be the central oncogenic trigger in T cell acute lymphoblastic leukemia (T-ALL), in which the majority of human malignancies have acquired mutations that lead to constitutive activation of Notch1 signaling.", "In a forward genetic screen for mutations that alter intracellular Notch receptor trafficking in Drosophila melanogaster, we recovered mutants that disrupt genes encoding serine palmitoyltransferase and acetyl-CoA carboxylase.", "Signaling pathways have become a major source of targets for novel therapies in hepatocellular carcinoma (HCC). Survival benefits achieved with sorafenib, a multikinase inhibitor, are unprecedented and underscore the importance of improving our understanding of how signaling networks interact in transformed cells.", "Notch-1 immunoexpression is increased in Alzheimer's and Pick's disease", "(PSEN1) is the major locus for mutations causing familial Alzheimer's disease (FAD) and is also mutated in Pick disease of brain, familial acne inversa and dilated cardiomyopathy. It is a critical facilitator of Notch signalling and many other signalling pathways and protein cleavage events including production of the Amyloidβ (Aβ) peptide from the AMYLOID BETA A4 PRECURSOR PROTEIN (APP", "As beta-APP and Notch are both processed by gamma-secretase, we analyzed expression of the Notch signaling pathway in the adult DS brain and in a model system for DS, human trisomy 21 fibroblasts by quantitative PCR. In adult DS cortex we found that Notch1, Dll1 and Hes1 expression is up-regulated. Moreover, DS fibroblasts and Alzheimer disease cortex also show overexpression of Notch1 and Dll1, indicating that enhanced beta-APP processing found in both DS and AD could be instrumental in these changes", "A systems biology approach to Down syndrome: identification of Notch/Wnt dysregulation in a model of stem cells aging", "Notch3 gene has been recently identified as a causative gene for cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL)" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/17981814", "http://www.ncbi.nlm.nih.gov/pubmed/24101600", "http://www.ncbi.nlm.nih.gov/pubmed/21772710", "http://www.ncbi.nlm.nih.gov/pubmed/24252593", "http://www.ncbi.nlm.nih.gov/pubmed/24249312", "http://www.ncbi.nlm.nih.gov/pubmed/15640354", "http://www.ncbi.nlm.nih.gov/pubmed/19383720", "http://www.ncbi.nlm.nih.gov/pubmed/16126912", "http://www.ncbi.nlm.nih.gov/pubmed/24140581", "http://www.ncbi.nlm.nih.gov/pubmed/24191040", "http://www.ncbi.nlm.nih.gov/pubmed/23432468", "http://www.ncbi.nlm.nih.gov/pubmed/24244188", "http://www.ncbi.nlm.nih.gov/pubmed/19419698", "http://www.ncbi.nlm.nih.gov/pubmed/11244211", "http://www.ncbi.nlm.nih.gov/pubmed/16473372", "http://www.ncbi.nlm.nih.gov/pubmed/24159576", "http://www.ncbi.nlm.nih.gov/pubmed/20205843", "http://www.ncbi.nlm.nih.gov/pubmed/24107444" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D051880", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009154", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D059645" ]

[ "Both Cockayne syndrome protein B (CSB) and Mfd are involved in transcription-coupled repair. CSB is the human TCR coupling factor and Mfd is the bacterial TCR coupling factor. However, unlike Mfd, CSB does not act as a helicase nor does it dissociate stalled RNA polymerase II, suggesting a coupling mechanism in humans different from that in prokaryotes. Moreover, Mfd may be functionally distinct from its human CSB homolog in that it does not detectably contribute to the recovery of gene expression or global repair following oxidative damage." ]

[ "yes" ]

[ "In humans, the TCR coupling factor, CSB, plays a critical role in restoring transcription following both UV-induced and oxidative DNA damage. It also contributes indirectly to the global repair of some forms of oxidative DNA damage. The Escherichia coli homolog, Mfd, is similarly required for TCR of UV-induced lesions.", "Mfd may be functionally distinct from its human CSB homolog in that it does not detectably contribute to the recovery of gene expression or global repair following oxidative damage.", "CSB has an ATPase activity that is stimulated strongly by DNA; however, it neither acts as a helicase nor does it dissociate stalled RNA polymerase II, suggesting a coupling mechanism in humans different from that in prokaryotes. ", "In addition, these findings imply that Mfd may be functionally distinct from its human CSB homolog in that it does not detectably contribute to the recovery of gene expression or global repair following oxidative damage.", "In addition, these findings imply that Mfd may be functionally distinct from its human CSB homolog in that it does not detectably contribute to the recovery of gene expression or global repair following oxidative damage.", "In contrast, no difference was detected in the rate of transcription recovery in mfd, uvrA, fpg, nth, or polB dinB umuDC mutants relative to wild-type cells following oxidative damage" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/22427630", "http://www.ncbi.nlm.nih.gov/pubmed/8999876" ]

[]

[ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0050783", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0050784" ]

[ "Membrane scission is the final step in order to complete the budding process, pinching off of the vesicle. To promote membrane scission, dynamin proteins polymerize, wrap around, and constrict the membrane. The scission of biological membranes is facilitated by a variety of protein complexes that bind and manipulate lipid bilayers." ]

[]

[ "To promote membrane scission, dynamin proteins polymerize, wrap around, and constrict the membrane; however, the mechanism underlying their role in membrane fusion remains unclear.", " Its role in endocytosis may be mediated by its reported interaction with dynamin 2, a 100 kDa GTPase that polymerizes around the necks of budding vesicles and catalyzes membrane scission", "Because the neck's radius is, in general, finite, membrane scission and the consequent pinching off of the vesicle can only occur if it is narrowed to permit the necessary membrane topological reformation.", "Dynamin recruitment and membrane scission at the neck of a clathrin-coated pit.", "ESCRT-III is the final complex in the pathway that assembles on endosomes and executes membrane scission of intraluminal vesicles.", "The scission of biological membranes is facilitated by a variety of protein complexes that bind and manipulate lipid bilayers. ", "Dynamin-2 is a pleiotropic GTPase whose best-known function is related to membrane scission during vesicle budding from the plasma or Golgi membranes. ", " Force produced by actin similarly contributes in membrane scission in endocytosis or Golgi remodeling.", "Dynamin 2 (Dyn2) is a ~100kDa GTPase that assembles around the necks of nascent endocytic and Golgi vesicles and catalyzes membrane scission. ", "membrane scission protein dynamin-2.", " Finally, a membrane scission event must occur to release the free virion", " Furthermore, GTP-dependent membrane scission by dynamin was dramatically elevated by BAR domain proteins. ", "few can mediate membrane scission to complete the budding process." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/25429432", "http://www.ncbi.nlm.nih.gov/pubmed/24440309", "http://www.ncbi.nlm.nih.gov/pubmed/25783003", "http://www.ncbi.nlm.nih.gov/pubmed/25784211", "http://www.ncbi.nlm.nih.gov/pubmed/24102355", "http://www.ncbi.nlm.nih.gov/pubmed/24878737", "http://www.ncbi.nlm.nih.gov/pubmed/24753582", "http://www.ncbi.nlm.nih.gov/pubmed/24099087", "http://www.ncbi.nlm.nih.gov/pubmed/23252497", "http://www.ncbi.nlm.nih.gov/pubmed/24016602", "http://www.ncbi.nlm.nih.gov/pubmed/25353823", "http://www.ncbi.nlm.nih.gov/pubmed/25202029", "http://www.ncbi.nlm.nih.gov/pubmed/23297414", "http://www.ncbi.nlm.nih.gov/pubmed/25664996" ]

[]

[]

[ "The TP73 gene, due to the presence of two promoters (P1 and P2) in its 5' flanking region, encodes a fully transcriptionally active domain (TAp73) and the amino terminus deleted (ΔNp73). TAp73 possesses pro-apoptotic properties, while deltaNp73 has anti-apoptotic functions. Alternative 3'-end splicing results in generation of at least seven TAp73 distinctive isoforms ( α, β, γ, etc ).", "The Trp73 gene belongs to the p53 family of transcription factors and, like the other members, is transcribed into different isoforms [1-4]. TP73 gene contains two promoters, encoding the transcriptional domain-containing (TAp73) and the amino deleted (DNp73) isoforms [5, 6]. Furthermore alternative splicing at the 3'-end (to generate a, b, g, etc isoforms) and 5'-end (to generate D2, D3 and D2-3 isoforms) results in generation of at least 14 different transcripts, with different abilities to promote or repress apoptosis [7, 8]. (PMID: 22388545)" ]

[ "seven", "7" ]

[ "A member of the p53 family, p73, has several isoforms and differentially regulates transcription of genes involved in the control of the cell cycle and apoptosis.", "The p73 gene, a homologue of the p53 tumor suppressor, is expressed as TA and ΔN isoforms. TAp73 has similar activity as p53 and functions as a tumor suppressor whereas ΔNp73 has both pro- and anti-survival functions.", "Transcription from two different promoters on the p73 gene results in generation of transcriptionally active TAp73 isoforms and dominant negative DeltaNp73 isoforms with opposing pro- and anti-apoptotic functions.", "We have evaluated the differential expression and subcellular localization of the functionally distinct apoptotic (TA) and anti-apoptotic (DeltaN) isoforms of p73 in non-small cell lung cancer (NSCLC), their possible association with p53 expression and determined the methylation status of the two p73 gene promoters (P1 and P2) in this tumor type.", "The role of various p73 isoforms in tumorigenesis has been controversial. However, as we have recently shown, the generation of TAp73-deficient (TAp73(-/-)) mice reveals that TAp73 isoforms exert tumor-suppressive functions, indicating an emerging role for Trp-73 in the maintenance of genomic stability. Unlike mice lacking all p73 isoforms, TAp73(-/-) mice show a high incidence of spontaneous tumors.", "Alternative promoters and N-terminal splicing result in the transcription and processing of either full-length (TA) or N-terminally truncated (deltaN) p73 isoforms. TAp73 possesses pro-apoptotic functions, while deltaNp73 has anti-apoptotic properties via functional inhibition of TAp73 and p53.", "The p73 gene is able to encode transcriptionaly active TAp73, as well as a dominant-negatively acting DeltaNp73 transcript isoforms.", "Since some mutant p53 proteins and ΔNp73 isoforms form heterocomplexes with TAp73, we asked whether p53 isoforms can do the same and potentially act as dominant-negative inhibitors of TAp73.", "p73, a p53 family tumor suppressor, is expressed as TA and ΔN isoforms.", "p73 is expressed as TA and ΔN isoforms, both of which are implicated in tumor suppression and/or promotion.", "We found that TAp73 isoforms are down regulated in oocytes from women older than 38 years.", "p73 possesses an extrinsic P1 promoter and an intrinsic P2 promoter controlling the expression of the pro-apoptotic TAp73 isoforms and the anti-apoptotic ΔΝp73 isoforms respectively.", "BRCA1-deficient ovarian carcinoma cells exhibit hypermethylation within a p73 regulatory region, which includes the binding site for the p73 transcriptional repressor ZEB1, leading to the abrogation of ZEB1 binding and increased expression of transactivating p73 isoforms (TAp73).", "In this study, we investigated the expression and subcellular distribution of two N-terminal isoforms, TAp73 and ΔNp73, in medulloblastoma cells using immunofluorescence microscopy.", "Proteasomal degradation of p73 is mediated by polyubiquitination-dependent and -independent processes both of which appear, thus far, to lack selectivity for the TAp73 and DeltaNp73 isoforms.", "In general, TAp73 isoforms show proapoptotic activities, whereas members of the N-terminally truncated (ΔN) p73 subfamily that lack the transactivation domain show antiapoptotic functions.", "The p73 gene possesses an extrinsic P1 promoter and an intrinsic P2 promoter, resulting in TAp73 and DeltaNup73 isoforms, respectively.", "Mice with a complete deficiency of p73 have severe neurological and immunological defects due to the absence of all TAp73 and DeltaNp73 isoforms.", "Moreover, we also found that subcellular location of p73 isoforms changes with the culture density increases.", "Moreover, ectopic expression of DeltaNp73alpha (but not other p73 isoforms) increased alphaB-crystallin mRNA levels in the absence of p53.", "Like wt p53, TAp63 and TAp73 isoforms transactivate target genes that activate apoptosis signaling pathways.", "The TP73 gene gives rise to transactivation domain-p73 isoforms (TAp73) as well as DeltaNp73 variants with a truncated N terminus.", "In contrast, antiapoptotic DeltaNp73 isoforms lack the TA domain and are dominant-negative inhibitors of p53 and TAp73.", "The isoforms TAp63 and TAp73 transactivate p53 target genes and induce apoptosis, whereas the isoforms DeltaNp63 and DeltaNp73 lack transactivation and might have dominant-negative effects in p53 family members.", "The expression of all 5 N-terminal isoforms (TAp73, DeltaNp73, DeltaN'p73, Ex2p73 and Ex2/3p73) was measured by real-time RT-PCR and p53 status was analyzed by immunohistochemistry. TAp73, DeltaNp73 and DeltaN'p73 were significantly upregulated in tumors.", "Consequently, different p73 isoforms can be degraded by calpains, i.e., both N-terminal isoforms (TAp73 and DeltaNp73) as well as the C-terminal isoforms (alpha, beta, gamma, delta).", "Variants lacking the TA domain (DeltaN isoforms) are induced by TAp73 and by p53, and inhibit their transcriptional activity.", "Indeed, tazarotene modulates the expression of the p73 gene in immortalized keratinocyte cell lines by inducing the pro-apoptotic and anti-proliferative TAp73 isoforms and by repressing the anti-apoptotic and pro-proliferative DeltaNp73 isoforms.", "p73, the first p53 gene homologue, encodes an array of p73 proteins including p73 alpha full-length (TAp73 alpha) and amino-truncated isoforms (Delta Np73 alpha), two proteins with opposite biological functions.", "We further showed that DeltaNp73 is a potent transdominant inhibitor of wild-type p53 and TAp73 in cultured human tumor cells by efficiently counteracting their target gene transactivations, apoptosis, and growth suppression functions (A.", "In developing sympathetic neurons of mice, p73 is predominantly expressed as a truncated anti-apoptotic isoform (DeltaNp73), which antagonizes both p53 and the full-length p73 protein (TAp73).", "Interestingly, expression of the Delta Np73 is strongly up-regulated by the TA isoforms and by p53, thus creating a feedback loop that tightly regulates the function of TAp73 and more importantly of p53." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/21946516", "http://www.ncbi.nlm.nih.gov/pubmed/22457351", "http://www.ncbi.nlm.nih.gov/pubmed/19139399", "http://www.ncbi.nlm.nih.gov/pubmed/16773194", "http://www.ncbi.nlm.nih.gov/pubmed/23271007", "http://www.ncbi.nlm.nih.gov/pubmed/21807636", "http://www.ncbi.nlm.nih.gov/pubmed/19885566", "http://www.ncbi.nlm.nih.gov/pubmed/20615966", "http://www.ncbi.nlm.nih.gov/pubmed/20926182", "http://www.ncbi.nlm.nih.gov/pubmed/22388545", "http://www.ncbi.nlm.nih.gov/pubmed/16254107", "http://www.ncbi.nlm.nih.gov/pubmed/18342333", "http://www.ncbi.nlm.nih.gov/pubmed/15059898", "http://www.ncbi.nlm.nih.gov/pubmed/12235210", "http://www.ncbi.nlm.nih.gov/pubmed/20298673", "http://www.ncbi.nlm.nih.gov/pubmed/21643019", "http://www.ncbi.nlm.nih.gov/pubmed/23470527", "http://www.ncbi.nlm.nih.gov/pubmed/11753569", "http://www.ncbi.nlm.nih.gov/pubmed/15610529", "http://www.ncbi.nlm.nih.gov/pubmed/14634023", "http://www.ncbi.nlm.nih.gov/pubmed/19861456", "http://www.ncbi.nlm.nih.gov/pubmed/12897129", "http://www.ncbi.nlm.nih.gov/pubmed/15975558", "http://www.ncbi.nlm.nih.gov/pubmed/12920125", "http://www.ncbi.nlm.nih.gov/pubmed/14676279", "http://www.ncbi.nlm.nih.gov/pubmed/15781249", "http://www.ncbi.nlm.nih.gov/pubmed/21852228", "http://www.ncbi.nlm.nih.gov/pubmed/16467208", "http://www.ncbi.nlm.nih.gov/pubmed/16322298", "http://www.ncbi.nlm.nih.gov/pubmed/19777343", "http://www.ncbi.nlm.nih.gov/pubmed/18546269", "http://www.ncbi.nlm.nih.gov/pubmed/15138575", "http://www.ncbi.nlm.nih.gov/pubmed/11830511", "http://www.ncbi.nlm.nih.gov/pubmed/12944917", "http://www.ncbi.nlm.nih.gov/pubmed/18350258", "http://www.ncbi.nlm.nih.gov/pubmed/15803372", "http://www.ncbi.nlm.nih.gov/pubmed/17626635", "http://www.ncbi.nlm.nih.gov/pubmed/22056305", "http://www.ncbi.nlm.nih.gov/pubmed/20146801", "http://www.ncbi.nlm.nih.gov/pubmed/19148480", "http://www.ncbi.nlm.nih.gov/pubmed/18477895", "http://www.ncbi.nlm.nih.gov/pubmed/19509292", "http://www.ncbi.nlm.nih.gov/pubmed/20733477", "http://www.ncbi.nlm.nih.gov/pubmed/20803057", "http://www.ncbi.nlm.nih.gov/pubmed/16964385", "http://www.ncbi.nlm.nih.gov/pubmed/20842728", "http://www.ncbi.nlm.nih.gov/pubmed/20581467", "http://www.ncbi.nlm.nih.gov/pubmed/19615968", "http://www.ncbi.nlm.nih.gov/pubmed/23159862", "http://www.ncbi.nlm.nih.gov/pubmed/16083956", "http://www.ncbi.nlm.nih.gov/pubmed/17076661", "http://www.ncbi.nlm.nih.gov/pubmed/19671150", "http://www.ncbi.nlm.nih.gov/pubmed/18039564", "http://www.ncbi.nlm.nih.gov/pubmed/18611950", "http://www.ncbi.nlm.nih.gov/pubmed/18469517", "http://www.ncbi.nlm.nih.gov/pubmed/16380414", "http://www.ncbi.nlm.nih.gov/pubmed/17029218", "http://www.ncbi.nlm.nih.gov/pubmed/17047653", "http://www.ncbi.nlm.nih.gov/pubmed/15889017", "http://www.ncbi.nlm.nih.gov/pubmed/22508983", "http://www.ncbi.nlm.nih.gov/pubmed/22484480", "http://www.ncbi.nlm.nih.gov/pubmed/20528922", "http://www.ncbi.nlm.nih.gov/pubmed/20194434", "http://www.ncbi.nlm.nih.gov/pubmed/23414597", "http://www.ncbi.nlm.nih.gov/pubmed/20807817", "http://www.ncbi.nlm.nih.gov/pubmed/11859407", "http://www.ncbi.nlm.nih.gov/pubmed/18256531", "http://www.ncbi.nlm.nih.gov/pubmed/23436675", "http://www.ncbi.nlm.nih.gov/pubmed/23362263", "http://www.ncbi.nlm.nih.gov/pubmed/23188674", "http://www.ncbi.nlm.nih.gov/pubmed/18583365", "http://www.ncbi.nlm.nih.gov/pubmed/21459846", "http://www.ncbi.nlm.nih.gov/pubmed/15752257", "http://www.ncbi.nlm.nih.gov/pubmed/16630058", "http://www.ncbi.nlm.nih.gov/pubmed/17430565", "http://www.ncbi.nlm.nih.gov/pubmed/18421303", "http://www.ncbi.nlm.nih.gov/pubmed/22740507", "http://www.ncbi.nlm.nih.gov/pubmed/17446929", "http://www.ncbi.nlm.nih.gov/pubmed/17912537", "http://www.ncbi.nlm.nih.gov/pubmed/15741235", "http://www.ncbi.nlm.nih.gov/pubmed/15467455", "http://www.ncbi.nlm.nih.gov/pubmed/16290057", "http://www.ncbi.nlm.nih.gov/pubmed/19103865", "http://www.ncbi.nlm.nih.gov/pubmed/19363520", "http://www.ncbi.nlm.nih.gov/pubmed/16980297", "http://www.ncbi.nlm.nih.gov/pubmed/17637683", "http://www.ncbi.nlm.nih.gov/pubmed/20613985" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D020033" ]

[ "In Saccharomyces cerevisiae, transcriptional responses to copper deficiency are mediated by the copper-responsive transcription factor Mac1. Ace1 mediates copper-induced gene expression in cells exposed to stressful levels of copper salts, whereas Mac1 activates a subset of genes under copper-deficient conditions." ]

[ "yes" ]

[ "Low-affinity copper transporter CTR2 is regulated by copper-sensing transcription factor Mac1p in Saccharomyces cerevisiae.", "The copper-depletion induced CTR2 transcription can be abrogated by genetic deletion of copper-sensing transcription factor Mac1p", "Taken together, our results suggest that Mac1p can activate the expression of vacuolar copper transporter Ctr2p in response to copper deficiency, resulting in yeast resistance to copper starvation.", "The ablation of either MAC1 or AFT1 also abrogated CTR2 expression induced by copper depletion", "Our further study revealed that exogenous Aft1p upregulates CTR2 transcription only in the presence of Mac1p, whereas exogenous Mac1p upregulates CTR2 transcription only in the presence of Aft1p.", "We previously reported that CTR2 can be upregulated by copper deficiency via copper-sensing transcription factor Mac1p.", "In Saccharomyces cerevisiae, transcriptional responses to copper deficiency are mediated by the copper-responsive transcription factor Mac1", "Although Mac1 activates the transcription of genes involved in high affinity copper uptake during periods of deficiency, little is known about the mechanisms by which Mac1 senses or responds to reduced copper availability. ", "The catalytic activity of Sod1 is essential for Mac1 activation and promotes a regulated increase in binding of Mac1 to copper response elements in the promoter regions of genomic Mac1 target genes.", "In Saccharomyces cerevisiae, copper ions regulate gene expression through the two transcriptional activators, Ace1 and Mac1.", "Ace1 mediates copper-induced gene expression in cells exposed to stressful levels of copper salts, whereas Mac1 activates a subset of genes under copper-deficient conditions.", "Taken together, our results suggest that Mac1p can activate the expression of vacuolar copper transporter Ctr2p in response to copper deficiency, resulting in yeast resistance to copper starvation.", "In Saccharomyces cerevisiae, transcriptional responses to copper deficiency are mediated by the copper-responsive transcription factor Mac1.", "We previously reported that CTR2 can be upregulated by copper deficiency via copper-sensing transcription factor Mac1p.", "The yeast Mac1 protein is a copper-sensing transcription factor that is essential for both the activation and inactivation of genes required for high affinity copper ion transport.", "The copper-depletion induced CTR2 transcription can be abrogated by genetic deletion of copper-sensing transcription factor Mac1p. ", "Copper-mediated repression of the activation domain in the yeast Mac1p transcription factor.", "We previously reported that CTR2 can be upregulated by copper deficiency via copper-sensing transcription factor Mac1p. ", "In this study, we found that copper depletion can upregulate yeast CTR2 gene transcription while copper overload downregulate it. The copper-depletion induced CTR2 transcription can be abrogated by genetic deletion of copper-sensing transcription factor Mac1p." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/22445756", "http://www.ncbi.nlm.nih.gov/pubmed/9159110", "http://www.ncbi.nlm.nih.gov/pubmed/9430656", "http://www.ncbi.nlm.nih.gov/pubmed/10922376", "http://www.ncbi.nlm.nih.gov/pubmed/18977757", "http://www.ncbi.nlm.nih.gov/pubmed/22683637", "http://www.ncbi.nlm.nih.gov/pubmed/21489137" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D003300", "http://amigo.geneontology.org/amigo/term/GO:0046688" ]

[ "Eukaryotic DNA replication terminates when replisomes from adjacent replication origins converge. Termination involves local completion of DNA synthesis, decatenation of daughter molecules and replisome disassembly. DNA synthesis does not slow detectably as forks approach each other, and leading strands pass each other unhindered before undergoing ligation to downstream lagging strands. Dissociation of the replicative CMG helicase (comprising CDC45, MCM2-7 and GINS) occurs only after the final ligation step, and is not required for completion of DNA synthesis, strongly suggesting that converging CMGs pass one another and dissociate from double-stranded DNA. This termination mechanism allows rapid completion of DNA synthesis while avoiding premature replisome disassembly." ]

[]

[ "Eukaryotic DNA replication terminates when replisomes from adjacent replication origins converge. Termination involves local completion of DNA synthesis, decatenation of daughter molecules and replisome disassembly.", "We show that DNA synthesis does not slow detectably as forks approach each other, and that leading strands pass each other unhindered before undergoing ligation to downstream lagging strands. Dissociation of the replicative CMG helicase (comprising CDC45, MCM2-7 and GINS) occurs only after the final ligation step, and is not required for completion of DNA synthesis, strongly suggesting that converging CMGs pass one another and dissociate from double-stranded DNA. This termination mechanism allows rapid completion of DNA synthesis while avoiding premature replisome disassembly" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/26322582" ]

[]

[ "http://amigo.geneontology.org/amigo/term/GO:2000621", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004261", "http://amigo.geneontology.org/amigo/term/GO:0097047", "http://amigo.geneontology.org/amigo/term/GO:0071170", "http://www.uniprot.org/uniprot/RTP_BACPZ", "http://www.uniprot.org/uniprot/RTP_BACVA", "http://amigo.geneontology.org/amigo/term/GO:0006274", "http://amigo.geneontology.org/amigo/term/GO:0071946" ]

[ "Ras proteins are proto-oncogenes that are frequently mutated in human cancers. Three closely related isoforms, HRAS, KRAS and NRAS, are expressed in all cells and have overlapping but distinctive functions.", "H-ras, N-ras, and K-ras are canonical ras gene family members frequently activated by point mutation in human cancers and coding for 4 different, highly related protein isoforms (H-Ras, N-Ras, K-Ras4A, and K-Ras4B)" ]

[ "H-Ras", "N-Ras", "K-Ras4A", "K-Ras4B" ]

[ "The major Ras isoforms (K, H, and N) ", "Mutations in Ras isoforms such as K-Ras, N-Ras, and H-Ras contribute to roughly 85, 15, and 1% of human cancers, respectively.", "the Ras isoforms (H, N and K) ", "The mutant forms of KRas, NRas and HRas", " lipidated Ras isoforms (H-Ras and N-Ras)", ": H-Ras, K-Ras, and N-Ras regulate cellular growth and survival and are often activated by somatic mutation in human tumors.", "Human tumours frequently express Ras proteins (Ha-, Ki-, N-Ras) ", " There are three major ras isoforms: H-, N- and K-Ras. ", "All mammalian cells express 3 closely related Ras proteins, termed H-Ras, K-Ras, and N-Ras", "hree closely related isoforms, HRAS, KRAS and NRAS, ", "H-ras, N-ras, and K-ras are canonical ras gene family members frequently activated by point mutation in human cancers and coding for 4 different, highly related protein isoforms (H-Ras, N-Ras, K-Ras4A, and K-Ras4B).", "he 3 Ras isoforms-H-Ras, K-Ras, and N-Ras-", "In this study, we compared the leukemogenic potential of activated NRAS, KRAS, and HRAS in the same bone marrow transduction/transplantation model system. ", "H-Ras, K-Ras, and N-Ras regulate cellular growth and survival and are often activated by somatic mutation in human tumors.", "Ras proteins are small GTPase functioning as molecular switches that, in response to particular extracellular signalling, as growth factors, activate a diverse array of intracellular effector cascades regulating cell proliferation, differentiation and apoptosis. Human tumours frequently express Ras proteins (Ha-, Ki-, N-Ras) activated by point mutations which contribute to malignant phenotype, including invasiveness and angiogenesis.", "Ras small GTPases function as transducers of extracellular signals regulating cell survival, growth and differentiation. There are three major ras isoforms: H-, N- and K-Ras. ", "All mammalian cells express 3 closely related Ras proteins, termed H-Ras, K-Ras, and N-Ras, that promote oncogenesis when they are mutationally activated at codon 12, 13, or 61.", "Ras proteins are proto-oncogenes that are frequently mutated in human cancers. Three closely related isoforms, HRAS, KRAS and NRAS, are expressed in all cells and have overlapping but distinctive functions.", "H-ras, N-ras, and K-ras are canonical ras gene family members frequently activated by point mutation in human cancers and coding for 4 different, highly related protein isoforms (H-Ras, N-Ras, K-Ras4A, and K-Ras4B)" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/24194124", "http://www.ncbi.nlm.nih.gov/pubmed/21924373", "http://www.ncbi.nlm.nih.gov/pubmed/22648805", "http://www.ncbi.nlm.nih.gov/pubmed/21779492", "http://www.ncbi.nlm.nih.gov/pubmed/23103856", "http://www.ncbi.nlm.nih.gov/pubmed/21779495", "http://www.ncbi.nlm.nih.gov/pubmed/22981836", "http://www.ncbi.nlm.nih.gov/pubmed/23496764", "http://www.ncbi.nlm.nih.gov/pubmed/22589270", "http://www.ncbi.nlm.nih.gov/pubmed/23871832", "http://www.ncbi.nlm.nih.gov/pubmed/23412389", "http://www.ncbi.nlm.nih.gov/pubmed/24247240", "http://www.ncbi.nlm.nih.gov/pubmed/17671181" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D020033", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011905", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0005099", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D015689", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0032856", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D018631", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016283" ]

[ "Endoplasmic reticulum aminopeptidase 2 (ERAP2) is localized to the luminal side of the endoplasmic reticulum." ]

[ "luminal side of the endoplasmic reticulum" ]

[ "The human endoplasmic reticulum aminopeptidase (ERAP) 1 and 2 proteins ", "They are categorized as a unique class of proteases based on their subcellular localization on the luminal side of the endoplasmic reticulum. ", "endoplasmic reticulum aminopeptidase 2 (ERAP2) ", "ERAP2 is a proteolytic enzyme set in the endoplasmic reticulum (ER) ", "both A-LAP and L-RAP are retained in the endoplasmic reticulum" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/23988446", "http://www.ncbi.nlm.nih.gov/pubmed/23946506", "http://www.ncbi.nlm.nih.gov/pubmed/16054015" ]

[ { "p": "http://purl.uniprot.org/core/encodedBy", "s": "http://purl.uniprot.org/uniprot/A6QPT7", "o": "http://linkedlifedata.com/resource/#_41365150543700A" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_413651505437008", "o": "Endoplasmic reticulum aminopeptidase 2" }, { "p": "http://www.w3.org/2004/02/skos/core#prefLabel", "s": "http://linkedlifedata.com/resource/#_41365150543700A", "o": "ERAP2" }, { "p": "http://purl.uniprot.org/core/encodedBy", "s": "http://purl.uniprot.org/uniprot/Q5RFP3", "o": "http://linkedlifedata.com/resource/#_513552465033009" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_513552465033007", "o": "Endoplasmic reticulum aminopeptidase 2" }, { "p": "http://www.w3.org/2004/02/skos/core#prefLabel", "s": "http://linkedlifedata.com/resource/#_513552465033009", "o": "ERAP2" }, { "p": "http://purl.uniprot.org/core/encodedBy", "s": "http://purl.uniprot.org/uniprot/Q6P179", "o": "http://linkedlifedata.com/resource/#_513650313739001B" }, { "p": "http://www.w3.org/2004/02/skos/core#altLabel", "s": "http://linkedlifedata.com/resource/#_513650313739001B", "o": "LRAP" }, { "p": "http://www.w3.org/2004/02/skos/core#prefLabel", "s": "http://linkedlifedata.com/resource/#_513650313739001B", "o": "ERAP2" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_5136503137390017", "o": "Leukocyte-derived arginine aminopeptidase" }, { "p": "http://purl.uniprot.org/core/shortName", "s": "http://linkedlifedata.com/resource/#_5136503137390017", "o": "L-RAP" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_5136503137390016", "o": "Endoplasmic reticulum aminopeptidase 2" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A14198238", "o": "29499" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A14201379", "o": "L-RAP" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C1836110", "o": "http://linkedlifedata.com/resource/umls/label/A11966235" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A14198239", "o": "LRAP" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C1836110", "o": "http://linkedlifedata.com/resource/umls/label/A17746860" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A11966235", "o": "ENDOPLASMIC RETICULUM AMINOPEPTIDASE 2" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C1836110", "o": "http://linkedlifedata.com/resource/umls/label/A14198238" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C1836110", "o": "http://linkedlifedata.com/resource/umls/label/A16703451" }, { "p": "http://linkedlifedata.com/resource/umls/altMetaMap", "s": "http://linkedlifedata.com/resource/umls/id/C1836110", "o": "http://linkedlifedata.com/resource/umls/label/A17731032" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A11951913", "o": "ERAP2" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A16703451", "o": "leukocyte-derived arginine aminopeptidase" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A14203968", "o": "ERAP2 gene" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C1836110", "o": "http://linkedlifedata.com/resource/umls/label/A12009126" }, { "p": "http://linkedlifedata.com/resource/umls/prefMetaMap", "s": "http://linkedlifedata.com/resource/umls/id/C1836110", "o": "http://linkedlifedata.com/resource/umls/label/A14203968" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C1836110", "o": "http://linkedlifedata.com/resource/umls/label/A11951913" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A14198238", "o": "endoplasmic reticulum aminopeptidase 2" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A12009126", "o": "LEUKOCYTE-DERIVED ARGININE AMINOPEPTIDASE" }, { "p": "http://linkedlifedata.com/resource/umls/altMetaMap", "s": "http://linkedlifedata.com/resource/umls/id/C1836110", "o": "http://linkedlifedata.com/resource/umls/label/A14198239" }, { "p": "http://linkedlifedata.com/resource/umls/altMetaMap", "s": "http://linkedlifedata.com/resource/umls/id/C1836110", "o": "http://linkedlifedata.com/resource/umls/label/A14201379" }, { "p": "http://linkedlifedata.com/resource/umls/altMetaMap", "s": "http://linkedlifedata.com/resource/umls/id/C1836110", "o": "http://linkedlifedata.com/resource/umls/label/A11966234" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A14198239", "o": "29499" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A14201379", "o": "29499" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A16703451", "o": "29499" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A17731032", "o": "29499" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A17746860", "o": "29499" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A18467226", "o": "C503944" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C1609313", "o": "http://linkedlifedata.com/resource/umls/label/A8599584" }, { "p": "http://linkedlifedata.com/resource/umls/prefMetaMap", "s": "http://linkedlifedata.com/resource/umls/id/C1609313", "o": "http://linkedlifedata.com/resource/umls/label/A18467226" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A9368721", "o": "leukocyte-derived arginine aminopeptidase, human" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C1609313", "o": "http://linkedlifedata.com/resource/umls/label/A9368721" }, { "p": "http://linkedlifedata.com/resource/umls/altMetaMap", "s": "http://linkedlifedata.com/resource/umls/id/C1609313", "o": "http://linkedlifedata.com/resource/umls/label/A8599671" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A9373187", "o": "endoplasmic reticulum aminopeptidase 2, human" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A18467226", "o": "ERAP2 protein, human" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A8599671", "o": "LRAP protein, human" }, { "p": "http://www.w3.org/2008/05/skos-xl#prefLabel", "s": "http://linkedlifedata.com/resource/umls/id/C1609313", "o": "http://linkedlifedata.com/resource/umls/label/A18467226" }, { "p": "http://linkedlifedata.com/resource/umls/altMetaMap", "s": "http://linkedlifedata.com/resource/umls/id/C1609313", "o": "http://linkedlifedata.com/resource/umls/label/A9373187" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A8599584", "o": "L-RAP protein, human" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A8599584", "o": "C503944" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A8599671", "o": "C503944" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A9368721", "o": "C503944" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A9373187", "o": "C503944" }, { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A14198238", "o": "HUGO" }, { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A14198239", "o": "HUGO" }, { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A14201379", "o": "HUGO" }, { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A16703451", "o": "HUGO" }, { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A17731032", "o": "HUGO" }, { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A17746860", "o": "HUGO" } ]

[ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0060341", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0008104", "http://www.uniprot.org/uniprot/ERAP2_PONAB", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0051179", "http://www.uniprot.org/uniprot/ERAP2_HUMAN", "http://www.uniprot.org/uniprot/ERAP2_BOVIN" ]

[ "There is not clear evidence that thyronamines have direct effect on adipose tissue" ]

[ "no" ]

[ "In conclusion, trace amines and thyronamines are negative inotropic agents.", "Their in vivo administration induces effects opposite to those induced by thyroid hormone, including lowering of body temperature." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/17579492", "http://www.ncbi.nlm.nih.gov/pubmed/17912534", "http://www.ncbi.nlm.nih.gov/pubmed/6094171", "http://www.ncbi.nlm.nih.gov/pubmed/20880963", "http://www.ncbi.nlm.nih.gov/pubmed/20005733", "http://www.ncbi.nlm.nih.gov/pubmed/18486124", "http://www.ncbi.nlm.nih.gov/pubmed/19273499", "http://www.ncbi.nlm.nih.gov/pubmed/22016721", "http://www.ncbi.nlm.nih.gov/pubmed/21664427", "http://www.ncbi.nlm.nih.gov/pubmed/19116337", "http://www.ncbi.nlm.nih.gov/pubmed/21490071", "http://www.ncbi.nlm.nih.gov/pubmed/17204552" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D000273", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D050153", "http://www.biosemantics.org/jochem#4251308", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D019358", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D014024", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005218", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005223", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D017667" ]

[ "Alemtuzumab and Campath-1H are the names of anti-CD52 monoclonal antibody that is used for treatment of multiple sclerosis patients. It has been shown to be effective for treatment naive and treatment resistant multiple sclerosis patients." ]

[ "Alemtuzumab", "Campath-1H" ]

[ "Alemtuzumab offers induction strategy for very active relapsing MS patients who have failed conventional therapy, and possibly selected treatment-naive patients.", "Differential reconstitution of T cell subsets following immunodepleting treatment with alemtuzumab (anti-CD52 monoclonal antibody) in patients with relapsing-remitting multiple sclerosis.", "Alemtuzumab (anti-CD52 mAb) provides long-lasting disease activity suppression in relapsing-remitting multiple sclerosis (RRMS).", "Alemtuzumab, an anti-CD52 monoclonal antibody, increased the risk of thyroid dysfunction in CAMMS223, a phase 2 trial in relapsing-remitting multiple sclerosis.", "Since then, one phase II and two phase III trials have shown that alemtuzumab reduces the relapse rate, compared with the active comparator interferon beta-1a (IFNβ-1a), in treatment-naïve and treatment-experienced MS up to 10 years from disease onset. Furthermore, in two of these trials, alemtuzumab reduced the risk of accumulating disability compared with IFNβ-1a; indeed alemtuzumab treatment led to an improvement in disability and reduction in cerebral atrophy.", "Alemtuzumab is a humanized monoclonal antibody specific for the CD52 protein present at high levels on the surface of B and T lymphocytes. In clinical trials, alemtuzumab has shown a clinical benefit superior to that of interferon-β in relapsing-remitting multiple sclerosis patients.", "These results potentially help explain the level of immunocompetence observed in alemtuzumab-treated MS patients.", "Alemtuzumab was first used in multiple sclerosis in 1991. It is a monoclonal antibody which is directed against CD52, a protein of unknown function on lymphocytes. ", "Against an active comparator and the current first-line therapy for relapsing-remitting multiple sclerosis (interferon-beta), alemtuzumab showed a significant reduction in annualized relapse rate as well as a significant reduction in the accumulation of disability. ", "Alemtuzumab (previously known as Campath(®)) is a humanized monoclonal antibody directed against the CD52 antigen on mature lymphocytes that results in lymphopenia and subsequent modification of the immune repertoire. ", "Compared to interferon beta-1a, alemtuzumab reduced the relapse rate by 49%-74% (P < 0.0001), and in two studies it reduced the risk of sustained disability accumulation by 42%-71% (P < 0.01). In one study (Comparison of Alemtuzumab and Rebif Efficacy in Multiple Sclerosis; CARE-MS1), there was no significant difference compared to interferon, perhaps reflecting the surprisingly low frequency of disability events in the comparator group.", "Alemtuzumab has been submitted for licensing in relapsing-remitting multiple sclerosis in the United States and Europe.", "Alemtuzumab was associated with a greater chance of improved contrast sensitivity in patients with RRMS and may delay the worsening of visual function. ", "The anti-CD52 monoclonal antibody alemtuzumab reduced disease activity in a phase 2 trial of previously untreated patients with relapsing-remitting multiple sclerosis. ", "Alemtuzumab's consistent safety profile and benefit in terms of reductions of relapse support its use for patients with previously untreated relapsing-remitting multiple sclerosis; however, benefit in terms of disability endpoints noted in previous trials was not observed here. ", "Alemtuzumab, formally known as Campath-1H, is a humanized monoclonal antibody directed against CD52, a protein on the surface of lymphocytes and monocytes with unknown function. A single dose of alemtuzumab leads to a rapid, profound and prolonged lymphopenia. A Phase II trial has shown that alemtuzumab reduces the risk of relapse and accumulation of disability by over 70% compared with interferon beta in patients with early relapsing-remitting multiple sclerosis (MS).", "Alemtuzumab, targeting CD52 expressed on T-cells, B-cells, monocytes and macrophages, has also shown to be effective in early RRMS and phase III trials are currently ongoing. ", "monoclonal antibody therapy has provided the opportunity to rationally direct the therapeutic intervention by specifically targeting mechanisms of the immune system such as CD52 (alemtuzumab), CD25 (daclizumab), VLA-4 (natalizumab) and CD20 (rituximab)", "Alemtuzumab is a humanized monoclonal antibody targeting CD52, a broadly expressed cell surface molecule on immune cells.", "Alemtuzumab-treatment of MS patients with relapsing-remitting forms of the disease significantly reduced the risk of relapse and accumulation of disability compared to interferon β-1a treatment in a phase II trial. ", "Alemtuzumab (CD52-specific humanized monoclonal antibody) was found to be an effective therapy for treatment-naive patients with relapsing-remitting multiple sclerosis. ", "Alemtuzumab effectively reduced relapse rates and improved clinical scores in patients with active relapsing-remitting multiple sclerosis not controlled by interferon therapy.", "Alemtuzumab is an anti-CD52 monoclonal antibody with remarkable efficacy in relapsing multiple sclerosis (MS). ", "The anti-CD52 monoclonal antibody alemtuzumab reduces disease activity in previously untreated patients with relapsing-remitting multiple sclerosis. ", "For patients with first-line treatment-refractory relapsing-remitting multiple sclerosis, alemtuzumab could be used to reduce relapse rates and sustained accumulation of disability. ", "Campath-1H causes the immune response to change from the Th1 phenotype, suppressing multiple sclerosis disease activity, but permitting the generation of antibody-mediated thyroid autoimmunity.", "Campath-1H is a humanized monoclonal antibody directed at CD52 expressed on lymphocytes and other cells of the immune system. It has been tested extensively in lymphoid malignancies, autoimmune diseases including rheumatoid arthritis, multiple sclerosis, and organ transplantation.", "Campath 1-H (Alemtuzumab) is a humanised monoclonal antibody which targets the CD52 antigen, a low molecular weight glycoprotein present on the surface of most lymphocyte lineages, causing complement mediated lysis and rapid and prolonged T lymphocyte depletion. Following encouraging initial data from other centres we report our open label experience of using Campath 1-H as a treatment in aggressive relapsing multiple sclerosis in a consecutive series of 39 highly selected patients treated across three regional centres and followed for a mean of 1.89 years.", "Alemtuzumab, a humanized monoclonal antibody that targets CD52 on lymphocytes and monocytes, may be an effective treatment for early multiple sclerosis. ", "In patients with early, relapsing-remitting multiple sclerosis, alemtuzumab was more effective than interferon beta-1a but was associated with autoimmunity, most seriously manifesting as immune thrombocytopenic purpura.", "Alemtuzumab, a monoclonal antibody targeting CD52, is a highly promising agent currently being studied in two phase III clinical trials. In this review, data from the recently published phase II clinical trial in the treatment of early relapsing remitting MS is summarized and analyzed in light of the development of alemtuzumab for MS and its potential role in treating this disease is discussed.", "Alemtuzumab is a humanized monoclonal antibody against CD52, an antigen found on the surface of normal and malignant lymphocytes. It is approved for the treatment of B-cell chronic lymphocytic leukaemia and is undergoing Phase III clinical trials for the treatment of multiple sclerosis. ", "To assess the effect of systemic lymphocyte depletion on disease activity, seven patients with MS received a 10-day intravenous course of the humanised monoclonal antibody CAMPATH-1H (anti-CDw52).", "The effect of CAMPATH-1H on disease activity provides direct, but preliminary, evidence that disease activity in MS depends on the availability of circulating lymphocytes and can be prevented by lymphocyte depletion.", "The elective treatment of patients with multiple sclerosis, using a humanized anti-leukocyte (CD52) monoclonal antibody (Campath-1H), has illuminated mechanisms that underlie the clinical course of the disease. ", "Alemtuzumab is currently under review to treat relapsing multiple sclerosis (MS) in the United States, based on positive Phase II and Phase III trials in both treatment-naïve and treated relapsing MS patients. ", "Alemtuzumab has recently been approved by the European authorities for active relapsing MS, in essence as a first-line agent.", "Alemtuzumab is a humanized monoclonal antibody directed against CD52. " ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/23122652", "http://www.ncbi.nlm.nih.gov/pubmed/23122650", "http://www.ncbi.nlm.nih.gov/pubmed/24170099", "http://www.ncbi.nlm.nih.gov/pubmed/10482259", "http://www.ncbi.nlm.nih.gov/pubmed/20236038", "http://www.ncbi.nlm.nih.gov/pubmed/7914262", "http://www.ncbi.nlm.nih.gov/pubmed/15049789", "http://www.ncbi.nlm.nih.gov/pubmed/24116901", "http://www.ncbi.nlm.nih.gov/pubmed/23558379", "http://www.ncbi.nlm.nih.gov/pubmed/21550857", "http://www.ncbi.nlm.nih.gov/pubmed/23494602", "http://www.ncbi.nlm.nih.gov/pubmed/23448220", "http://www.ncbi.nlm.nih.gov/pubmed/23459567", "http://www.ncbi.nlm.nih.gov/pubmed/19740383", "http://www.ncbi.nlm.nih.gov/pubmed/24289293", "http://www.ncbi.nlm.nih.gov/pubmed/18946064", "http://www.ncbi.nlm.nih.gov/pubmed/22056965", "http://www.ncbi.nlm.nih.gov/pubmed/20088763", "http://www.ncbi.nlm.nih.gov/pubmed/22229582", "http://www.ncbi.nlm.nih.gov/pubmed/18075272", "http://www.ncbi.nlm.nih.gov/pubmed/24198283", "http://www.ncbi.nlm.nih.gov/pubmed/16231285", "http://www.ncbi.nlm.nih.gov/pubmed/8624684", "http://www.ncbi.nlm.nih.gov/pubmed/23759318", "http://www.ncbi.nlm.nih.gov/pubmed/19296065", "http://www.ncbi.nlm.nih.gov/pubmed/18283404", "http://www.ncbi.nlm.nih.gov/pubmed/18713579", "http://www.ncbi.nlm.nih.gov/pubmed/22252465", "http://www.ncbi.nlm.nih.gov/pubmed/23634277", "http://www.ncbi.nlm.nih.gov/pubmed/21899662", "http://www.ncbi.nlm.nih.gov/pubmed/23709214", "http://www.ncbi.nlm.nih.gov/pubmed/10568572", "http://www.ncbi.nlm.nih.gov/pubmed/17920549", "http://www.ncbi.nlm.nih.gov/pubmed/19878629" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D061067", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009103", "http://www.disease-ontology.org/api/metadata/DOID:2377", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D000911" ]

[ "Yes. SpliceR is an R package for classification of alternative splicing and prediction of coding potential from RNA-seq data." ]

[ "yes" ]

[ "spliceR: an R package for classification of alternative splicing and prediction of coding potential from RNA-seq data.", "Recent software improvements in full-length transcript deconvolution prompted us to develop spliceR, an R package for classification of alternative splicing and prediction of coding potential.", "spliceR uses the full-length transcript output from RNA-seq assemblers to detect single or multiple exon skipping, alternative donor and acceptor sites, intron retention, alternative first or last exon usage, and mutually exclusive exon events. For each of these events spliceR also annotates the genomic coordinates of the differentially spliced elements, facilitating downstream sequence analysis. For each transcript isoform fraction values are calculated to identify transcript switching between conditions. Lastly, spliceR predicts the coding potential, as well as the potential nonsense mediated decay (NMD) sensitivity of each transcript.", "Recent software improvements in full-length transcript deconvolution prompted us to develop spliceR, an R package for classification of alternative splicing and prediction of coding potential.", "Recent software improvements in full-length transcript deconvolution prompted us to develop spliceR, an R package for classification of alternative splicing and prediction of coding potential. ", "Recent software improvements in full-length transcript deconvolution prompted us to develop spliceR, an R package for classification of alternative splicing and prediction of coding potential." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/24655717" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D017398", "http://amigo.geneontology.org/amigo/term/GO:0000381", "http://amigo.geneontology.org/amigo/term/GO:0000380" ]

[ "Subgenual cingulate gyrus, the anterior limb of the capsula interna, nucleus accumbens, medial forebrain bundle, habenula, and caudate nucleus have been investigated as potential targeted for the deep brain stimulation of patients suffering from major depression." ]

[ "subgenual cingulate gyrus", "anterior limb of the capsula interna", "nucleus accumbens", "medial forebrain bundle", "habenula", "ventral caudate nucleus" ]

[ "Deep brain stimulation (DBS) is under scientific evaluation as a new treatment option for these treatment-resistant patients. First clinical studies with small samples have been stimulated at the subgenual cingulate gyrus (Cg25/24), the anterior limb of the capsula interna (ALIC), and the nucleus accumbens (NAcc). ", "New hypothesis-guided targets (e.g., medial forebrain bundle, habenula) are about to be assessed in clinical trials. ", "Deep brain stimulation (DBS) to the nucleus accumbens (NAcc-DBS) has antidepressant effects in patients suffering from treatment-resistant depression (TRD). ", "The ventral striatum, including the head of the caudate nucleus and the nucleus accumbens, is a putative target for deep brain stimulation (DBS) in the treatment of obsessive-compulsive disorder (OCD) and major depression (MD). ", "High frequency stimulation was successfully applied in several small samples of patients with treatment-resistant depression when the stimulation focused on different areas, e.g., nucleus accumbens, the lateral habenula or cortical areas.", "We recorded electrophysiological activity directly from the nucleus accumbens of five patients undergoing deep brain stimulation for treatment of refractory major depression. ", "Functional inhibition of the lateral habenula via deep brain stimulation (DBS) has antidepressive properties.", "Because a prominent clinical feature of depression is anhedonia--the inability to experience pleasure from previously pleasurable activities--and because there is clear evidence of dysfunctions of the reward system in depression, DBS to the nucleus accumbens might offer a new possibility to target depressive symptomatology in otherwise treatment-resistant depression.", "These preliminary findings suggest that DBS to the nucleus accumbens might be a hypothesis-guided approach for refractory major depression.", "Deep brain stimulation of the ventral caudate nucleus markedly improved symptoms of depression and anxiety until their remission, which was achieved at 6 months after the start of stimulation (HDRS < or = 7 and HARS < or = 10).", "No neuropsychological deterioration was observed, indicating that DBS of the ventral caudate nucleus could be a promising strategy in the treatment of refractory cases of both OCD and major depression.", "Comparisons of clinical outcomes and anatomical data on electrode positioning showed that caudate nucleus stimulation preferentially alleviated OCD manifestations, whereas nucleus accumbens stimulation improved depressive symptoms. " ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/24112897", "http://www.ncbi.nlm.nih.gov/pubmed/23230531", "http://www.ncbi.nlm.nih.gov/pubmed/17498883", "http://www.ncbi.nlm.nih.gov/pubmed/21736514", "http://www.ncbi.nlm.nih.gov/pubmed/19284243", "http://www.ncbi.nlm.nih.gov/pubmed/15481726", "http://www.ncbi.nlm.nih.gov/pubmed/22473055", "http://www.ncbi.nlm.nih.gov/pubmed/19137233", "http://www.ncbi.nlm.nih.gov/pubmed/17429407", "http://www.ncbi.nlm.nih.gov/pubmed/19092783", "http://www.ncbi.nlm.nih.gov/pubmed/18704495", "http://www.ncbi.nlm.nih.gov/pubmed/19727257", "http://www.ncbi.nlm.nih.gov/pubmed/16816792" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D003865", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D046690", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001921", "http://www.disease-ontology.org/api/metadata/DOID:1470" ]

[ "Yes, alemtuzumab (anti-CD52, Campath-1H) is effective for remission induction in patients diagnosed with T-cell prolymphocytic leukemia. Alemtuzumab can be administered in combination with other chemotherapeutic agents or as mono-therapy. Response rate to alemtuzumab is more than 90%. Alemtuzumab therapy is associated with improved survival of T-cell prolymphocytic leukemia patients." ]

[ "yes" ]

[ "Sequential chemoimmunotherapy of fludarabine, mitoxantrone, and cyclophosphamide induction followed by alemtuzumab consolidation is effective in T-cell prolymphocytic leukemia", "A central need in this historically refractory tumor is the controlled evaluation of multiagent chemotherapy and its combination with the currently most active single agent, alemtuzumab. ", "FMC-A is a safe and efficient protocol in T-PLL, which compares favorably to published data.", "Currently, the best treatment for T-PLL is IV alemtuzumab, which has resulted in very high response rates of more than 90% when given as frontline treatment and a significant improvement in survival. ", "The patient failed to respond to standard ALL induction chemotherapy, but achieved complete remission following treatment with a fludarabine and alemtuzumab-based regimen.", "Here we present a rare case of concurrent T-PLL and Kaposi sarcoma who achieved a complete hematologic and cytogenetic remission after a very short course of treatment with alemtuzumab.", " Recent studies with single-agent alemtuzumab, an anti-CD52 monoclonal antibody, have shown improved response rates and survival in patients with T-cell prolymphocytic leukemia and cutaneous T-cell lymphoma. ", "The CD52 antigen is expressed at high density on the malignant T-cells and therapy with alemtuzumab, a humanized IgG1 antibody that targets this antigen, has produced promising results. ", "With the introduction of alemtuzumab, most patients who progressed despite treatment with pentostatin had a major response with a complete remission rate higher than that obtained with pentostatin when used as a first line.", "Alemtuzumab (anti-CD52, Campath-1H) has recently been shown to be effective in the treatment of a range of hematological malignancies, including B-cell chronic lymphocytic leukemia and T-cell prolymphocytic leukemia.", "Here we report the outcome of two patients with CD4-positive T cell prolymphocytic leukemia treated with CAMPATH-1H. Both patients responded rapidly to treatment and subsequently developed CD4 lymphopenia.", "T-cell prolymphocytic leukemia (T-PLL) is a chemotherapy-resistant malignancy with a median survival of 7.5 months. Preliminary results indicated a high remission induction rate with the human CD52 antibody, CAMPATH-1H. ", "CAMPATH-1H (30 mg) was administered intravenously 3 times weekly until maximal response. The overall response rate was 76% with 60% CR and 16% partial remission (PR). These responses were durable with a median disease-free interval of 7 months (range, 4-45 months). ", "The conclusion is that CAMPATH-1H is an effective therapy in T-PLL, producing remissions in more than two thirds of patients. ", "For example, most patients with T-cell prolymphocytic leukemia, including those with large tumor burdens and high peripheral white blood cell counts, will enter complete remission using the antibody CAMPATH-1H without any evidence of tumor lysis.", "Overall response rate to FMC was 68%, comprising 6 complete remissions (all bone-marrow confirmed) and 11 partial remissions. Alemtuzumab consolidation increased the intent-to-treat overall response rate to 92% (12 complete remissions; 11 partial remissions). " ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/15453953", "http://www.ncbi.nlm.nih.gov/pubmed/10561018", "http://www.ncbi.nlm.nih.gov/pubmed/15757437", "http://www.ncbi.nlm.nih.gov/pubmed/12950233", "http://www.ncbi.nlm.nih.gov/pubmed/23512246", "http://www.ncbi.nlm.nih.gov/pubmed/22517037", "http://www.ncbi.nlm.nih.gov/pubmed/16720203", "http://www.ncbi.nlm.nih.gov/pubmed/16645226", "http://www.ncbi.nlm.nih.gov/pubmed/23211022", "http://www.ncbi.nlm.nih.gov/pubmed/23233647", "http://www.ncbi.nlm.nih.gov/pubmed/11535503", "http://www.ncbi.nlm.nih.gov/pubmed/11986948", "http://www.ncbi.nlm.nih.gov/pubmed/23645660", "http://www.ncbi.nlm.nih.gov/pubmed/15869731", "http://www.ncbi.nlm.nih.gov/pubmed/21948296", "http://www.ncbi.nlm.nih.gov/pubmed/17118783", "http://www.ncbi.nlm.nih.gov/pubmed/22649104" ]

[]

[ "http://www.biosemantics.org/jochem#4002029", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D015461", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012074" ]

[ "It has been reported that moon phases correlate with the incidence of aneurysmal subarachnoid hemorrhage due to ruptured intracranial aneurysms. However, other authors have found no correlation between incidence of aneurysmal SAH, location of the aneurysm, initial clinical presentation, or amount of subarachnoid blood and the lunar cycle." ]

[]

[ "Recently, it has been reported that moon phases correlate with the incidence of aneurysmal subarachnoid hemorrhage (SAH), however, another author found no such association. ", "We found no correlation between incidence of aneurysmal SAH, location of the aneurysm, initial clinical presentation, or amount of subarachnoid blood and the lunar cycle. ", "The moon influences neither the incidence of aneurysmal SAH nor the grade of initial neurological deterioration or amount of subarachnoid blood.", "We did not observe any significant impact of the lunar cycle on the incidence of aneurysmal subarachnoid haemorrhage in 717 consecutive patients (p=0.84).", "The impact of the lunar cycle on aneurysmal subarachnoid haemorrhage is a myth rather than reality.", "An incidence peak for aneurysm rupture (28 patients) was seen during the phase of new moon, which was statistically significant (p < 0.001).", "The lunar cycle seems to affect the incidence of intracranial aneurysm rupture, with the new moon being associated with an increased risk of aneurysmal SAH." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/19101078", "http://www.ncbi.nlm.nih.gov/pubmed/18353534", "http://www.ncbi.nlm.nih.gov/pubmed/23702791" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D017542", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D002532", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016081", "http://www.disease-ontology.org/api/metadata/DOID:10941" ]

[ "Telomerase reverse transcriptase (TERT) promoter are associated with shorter survival of glioblastoma patients. Prognostic value of TERT mutations for poor survival is largely due to their inverse correlation with IDH1 mutations." ]

[ "yes" ]

[ "Glioblastoma patients with TERT mutations showed a shorter survival than those without TERT mutations in univariate analysis (median, 9.3 vs. 10.5 months; P = 0.015) and multivariate analysis after adjusting for age and gender (HR 1.38, 95 % CI 1.01-1.88, P = 0.041). However, TERT mutations had no significant impact on patients' survival in multivariate analysis after further adjusting for other genetic alterations, or when primary and secondary glioblastomas were separately analysed. These results suggest that the prognostic value of TERT mutations for poor survival is largely due to their inverse correlation with IDH1 mutations, which are a significant prognostic marker of better survival in patients with secondary glioblastomas.", "Patients with tumors lacking hTERT expression/TA showed a significant survival benefit (Kaplan-Meier test, both P < .01), which, however, was based exclusively on the younger patient subgroup (≤60 y, both P < .005; >60 y, both ns). ", "Glioblastoma patients with TERT mutations showed a shorter survival than those without TERT mutations in univariate analysis (median, 9.3 vs" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/23393205", "http://www.ncbi.nlm.nih.gov/pubmed/24937153", "http://www.ncbi.nlm.nih.gov/pubmed/23955565" ]

[]

[ "http://www.disease-ontology.org/api/metadata/DOID:3073" ]

[ "Clinical trials have demonstrated that bapineuzumab, a humanized monoclonal antibody against the end terminus of amyloid plaques, is not effective for treatment of patients with Alzheimer's disease. The burden of beta amyloid plaques was reduced in response to bapineuzumab therapy. However, bapineuzumab therapy did not improve cognitive functioning and was associated with significant adverse effects in Alzheimer's disease patients." ]

[ "no" ]

[ " Thus far, results from two large phase 3 trial programs with bapineuzumab and solaneuzumab, respectively, have brought rather disappointing results.", "More recently, in phase III studies, bapineuzumab has been discontinued because it did not prove clinically effective (despite its significant effect on biomarkers), while solaneuzumab has been found effective in slowing AD progression. ", "Passive immunotherapy with monoclonal antibodies (mAbs) against Aβ is in late clinical development but recently the two most advanced mAbs, Bapineuzumab and Solanezumab, targeting an N-terminal or central epitope, respectively, failed to meet their target of improving or stabilizing cognition and function.", "The marginal effects observed in recent clinical studies of solanezumab, targeting monomeric Aβ, and bapineuzumab, targeting amyloid plaques, prompted expert comments that drug discovery efforts in Alzheimer's disease should focus on soluble forms of Aβ rather than fibrillar Aβ deposits found in amyloid plaques.", "Phase III trials showed that bapineuzumab failed to improve cognitive and functional performances in AD patients, and was associated with a high incidence of amyloid-related imaging abnormalities (ARIA).", "Clinical trials on various drugs, including AN1792, bapineuzumab, and solanezumab, have been carried out; however, all trials have failed to demonstrate apparent clinical benefits. ", "Despite the alteration in biochemical composition, all 3 immunized subjects exhibited continued cognitive decline.", "Despite negative topline phase 3 clinical trial results for bapineuzumab and solanezumab in mild to moderate AD, findings from these trials and recent advances suggest renewed optimism for anti-amyloid therapies. ", "The lack of progress in the development of disease-modifying therapy in Alzheimer's disease (AD) was highlighted recently by the cessation of a phase 3 clinical trial studying the effects of bapineuzumab on mild to moderate disease. No treatment benefit was apparent, whereas several serious side effects occurred more commonly in the treatment group compared to placebo. ", "Clinical studies using the N-terminal-directed anti-Aβ antibody bapineuzumab have demonstrated reduced brain PET-Pittsburg-B signals, suggesting the reduction of Aβ plaques, and reduced levels of total and phosphorylated tau protein in the CSF of treated AD patients. Preclinical studies using 3D6 (the murine form of bapineuzumab) have demonstrated resolution of Aβ plaque and vascular burdens, neuritic dystrophy, and preservation of synaptic density in the transgenic APP mouse models.", "The clinical results of the initial studies with bapineuzumab were equivocal in terms of cognitive benefit. The occurrence of vasogenic edema after bapineuzumab, and more rarely brain microhemorrhages (especially in Apo E ε4 carriers), has raised concerns on the safety of these antibodies directed against the N-terminus of the Aβ peptide. ", " The most advanced of these immunological approaches is bapineuzumab, composed of humanized anti-Aβ monoclonal antibodies, that has been tested in two Phase II trials, demonstrating to reduce Aβ burden in the brain of AD patients. However, the preliminary cognitive efficacy of bapineuzumab appears uncertain. The occurrence of vasogenic edema, especially in apolipoprotein E 4 carriers, may limit its clinical use and have led to abandon the highest dose of the drug (2 mg/kg).", "However, the preliminary cognitive efficacy of bapineuzumab, a humanized anti-Aβ monoclonal antibody, appears uncertain. Moreover, the occurrence of vasogenic edema and, more rarely, brain microhemorrhages, especially in apolipoprotein E ϵ4 carriers, have led to abandoning of the highest dose of the drug. ", "However, the preliminary equivocal cognitive results obtained with bapineuzumab as well as the detrimental cognitive effects observed with semagacestat, a potent γ-secretase inhibitor, raise the possibility that targeting Aβ may not be clinically efficacious in AD. ", "The patient received four bapineuzumab infusions over a 39 week period. During the course of this treatment, there was no remarkable change in cognitive impairment as determined by MMSE scores. Forty-eight days after the fourth bapineuzumab infusion was given, MRI revealed that the patient had developed lacunar infarcts and possible vasogenic edema, probably related to immunotherapy, but a subsequent MRI scan 38 days later demonstrated resolution of vasogenic edema. The patient expired due to acute congestive heart failure complicated by progressive AD and cerebrovascular accident 378 days after the first bapineuzumab infusion and 107 days after the end of therapy. Neuropathological and biochemical analysis did not produce evidence of lasting plaque regression or clearance of Aβ due to immunotherapy.", "These results suggest that, in this particular case, bapineuzumab immunotherapy neither resulted in detectable clearance of amyloid plaques nor prevented further cognitive impairment.", "Bapineuzumab has been shown to reduce Aβ burden in the brain of AD patients. However, its preliminary cognitive efficacy appears uncertain, particularly in ApoE ε4 carriers, and vasogenic edema may limit its clinical use. ", "Bapineuzumab appears capable of reducing the cerebral beta-amyloid peptide burden in patients with Alzheimer's disease. However, particularly in APOE 4 carriers, its ability to slow disease progression remains uncertain, and vasogenic edema - a dose-limiting and potentially severe adverse reaction - may limit its clinical applicability.", "The first is a phase 2 study of passive immunotherapy with bapineuzumab, a humanized anti-Abeta monoclonal antibody directed against the N-terminus of Abeta. This trial showed no differences within dose cohorts on the primary efficacy analysis. Exploratory analyses showed potential treatment differences on cognitive and functional endpoints in study completers and apolipoprotein E epsilon4 noncarriers. A safety concern was the occurrence of reversible vasogenic edema. ", "The first passive immunotherapy trial with bapineuzumab, a humanized monoclonal antibody against the end terminus of Abeta, also encountered some dose dependent adverse events during the Phase II portion of the study, vasogenic edema in 12 cases, which were significantly over represented in ApoE4 carriers." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/22529838", "http://www.ncbi.nlm.nih.gov/pubmed/21263194", "http://www.ncbi.nlm.nih.gov/pubmed/24255592", "http://www.ncbi.nlm.nih.gov/pubmed/22357853", "http://www.ncbi.nlm.nih.gov/pubmed/24086465", "http://www.ncbi.nlm.nih.gov/pubmed/24216217", "http://www.ncbi.nlm.nih.gov/pubmed/20929585", "http://www.ncbi.nlm.nih.gov/pubmed/24434253", "http://www.ncbi.nlm.nih.gov/pubmed/23599675", "http://www.ncbi.nlm.nih.gov/pubmed/20189881", "http://www.ncbi.nlm.nih.gov/pubmed/19674435", "http://www.ncbi.nlm.nih.gov/pubmed/23299380", "http://www.ncbi.nlm.nih.gov/pubmed/22506132", "http://www.ncbi.nlm.nih.gov/pubmed/23582316", "http://www.ncbi.nlm.nih.gov/pubmed/23847530", "http://www.ncbi.nlm.nih.gov/pubmed/21091109", "http://www.ncbi.nlm.nih.gov/pubmed/23555764", "http://www.ncbi.nlm.nih.gov/pubmed/21592055", "http://www.ncbi.nlm.nih.gov/pubmed/22815077", "http://www.ncbi.nlm.nih.gov/pubmed/23874844", "http://www.ncbi.nlm.nih.gov/pubmed/23574434", "http://www.ncbi.nlm.nih.gov/pubmed/23894286", "http://www.ncbi.nlm.nih.gov/pubmed/20205639", "http://www.ncbi.nlm.nih.gov/pubmed/23931438", "http://www.ncbi.nlm.nih.gov/pubmed/23809364", "http://www.ncbi.nlm.nih.gov/pubmed/20154508", "http://www.ncbi.nlm.nih.gov/pubmed/23210837", "http://www.ncbi.nlm.nih.gov/pubmed/23861639", "http://www.ncbi.nlm.nih.gov/pubmed/21501112", "http://www.ncbi.nlm.nih.gov/pubmed/20388189", "http://www.ncbi.nlm.nih.gov/pubmed/20497044", "http://www.ncbi.nlm.nih.gov/pubmed/23416764", "http://www.ncbi.nlm.nih.gov/pubmed/23085451", "http://www.ncbi.nlm.nih.gov/pubmed/22339463", "http://www.ncbi.nlm.nih.gov/pubmed/23568994", "http://www.ncbi.nlm.nih.gov/pubmed/23255116", "http://www.ncbi.nlm.nih.gov/pubmed/23663286", "http://www.ncbi.nlm.nih.gov/pubmed/22957288", "http://www.ncbi.nlm.nih.gov/pubmed/19923550", "http://www.ncbi.nlm.nih.gov/pubmed/24489866", "http://www.ncbi.nlm.nih.gov/pubmed/22305802", "http://www.ncbi.nlm.nih.gov/pubmed/20122289", "http://www.ncbi.nlm.nih.gov/pubmed/19585948" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013812", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016896", "http://www.disease-ontology.org/api/metadata/DOID:10652", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D000544" ]

[ "Two deiodinase polymorphisms are implicated in arterial hypertension: Ala92 type 2 deiodinase allele and rs7140952 polymorphism of DIO2", "At least two deiodinease polymorfisms are implicated in arterial hypertension:\nDIO 2 Thr92Ala\nrs7140952" ]

[ "rs7140952 polymorphism of DIO2", "rs7140952", "Ala92 type 2 deiodinase allele", "DIO 2 Thr92Ala" ]

[ "However, rs7140952 polymorphism is associated with components of metabolic syndrome including blood pressure and central obesity.", "Among euthyroid adults, the common Ala92 allele of the type 2 iodothyronine deiodinase increases risk for the development of hypertension. ", "Ala92 type 2 deiodinase allele increases risk for the development of hypertension.", "This study investigates the clinical and biochemical response to L-T4 replacement therapy in hypothyroid patients in correlation with genetic variation in Deiodinase type || (DIO2) gene. " ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/21415143", "http://www.ncbi.nlm.nih.gov/pubmed/17224473", "http://www.ncbi.nlm.nih.gov/pubmed/19178511", "http://www.ncbi.nlm.nih.gov/pubmed/18198294", "http://www.ncbi.nlm.nih.gov/pubmed/23329579", "http://www.ncbi.nlm.nih.gov/pubmed/19014646" ]

[]

[ "http://www.disease-ontology.org/api/metadata/DOID:10825", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D006973", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D007453", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011110", "http://www.disease-ontology.org/api/metadata/DOID:10763" ]

[ "Treatment of subclinical hypothyroidism is associated with fewer cardiovascular events in younger individuals, but this issue has not been resolved yet in elderly people." ]

[ "effective in younger individuals" ]

[ "sHT in older people should be not regarded as a unique condition, and moderately old patients (aged <70-75 y) could be considered clinically similar to the adult population, albeit with a higher optimal TSH target value. Conversely, the oldest old subjects should be carefully followed with a wait-and-see strategy, generally avoiding hormonal treatment. The decision to treat elderly people is still an unresolved clinical challenge--first, due to a lack of appropriately powered randomized controlled trials of L-T4 in sHT patients, examining cardiovascular hard endpoints in various classes of age; and second, because of the negative effects of possible overtreatment.", "Treatment of SCH with levothyroxine was associated with fewer IHD events in younger individuals, but this was not evident in older people. An appropriately powered randomized controlled trial of levothyroxine in SCH examining vascular outcomes is now warranted.", "SCH appears to influence the postoperative outcome for patients by increasing the development of postoperative atrial fibrillation. However, it is still unproven whether preoperative thyroxine replacement therapy for patients with SCH might prevent postoperative atrial fibrillation after CABG.", "Sustained normalization of thyroid function during l-T(4) replacement therapy significantly decreases baPWV in female subclinical hypothyroid patients with autoimmune chronic thyroiditis, suggesting the improvement of arterial stiffening and, consequently, possible prevention of cardiovascular disease.", "Our results suggest that L-T(4) replacement therapy may be especially beneficial in female subclinical hypothyroid patients with high baseline baPWV and pulse pressure. The beneficial effects of L-T(4) replacement therapy in decreasing arterial stiffening and thus preventing cardiovascular disease might be limited to this sub-population.", "Although a consensus is still lacking, the strongest evidence for a beneficial effect of levothyroxine replacement on markers of cardiovascular risk is the substantial demonstration that restoration of euthyroidism can lower both total and low-density lipoprotein-cholesterol levels in most patients with subclinical hypothyroidism.", "However, the actual effectiveness of thyroid hormone substitution in reducing the risk of cardiovascular events remains to be elucidated.", "Restoration of euthyroidism by levothyroxine (LT4) treatment may correct the lipid profile and cardiac abnormalities, especially in patients with an initially higher deviation from normality and higher serum TSH levels. Importantly, a strong association between SH and atherosclerotic cardiovascular disease, independent of the traditional risk factors, has been recently reported in a large cross-sectional survey (the Rotterdam Study). However, whether SH confers a high risk for cardiovascular disease, and whether LT4 therapy has a long-term benefit that clearly outweighs the risks of overzealous treatment in these individuals, remain topics of controversy." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/23559085", "http://www.ncbi.nlm.nih.gov/pubmed/16542047", "http://www.ncbi.nlm.nih.gov/pubmed/17544610", "http://www.ncbi.nlm.nih.gov/pubmed/22529180", "http://www.ncbi.nlm.nih.gov/pubmed/16026106", "http://www.ncbi.nlm.nih.gov/pubmed/17636722", "http://www.ncbi.nlm.nih.gov/pubmed/19463607", "http://www.ncbi.nlm.nih.gov/pubmed/19114542" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013812", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D002318", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D007037" ]

[ "YES:" ]

[ "yes" ]

[ "Our major finding is that repeated very intense exercise prolongs life span in well trained practitioners.", "Death rates declined with increased levels of total activity (estimated in kilocalories), and declined also with increased intensity of effort measured as from none, to light, to moderately vigorous or vigorous sports play. Death rates at any given quantity of physical exercise were lower for men playing moderately intense sports than for less vigorous men.", "he purpose of this study was to investigate if jogging, which can be very vigorous, is associated with increased all-cause mortality in men and women.", "This long-term study of joggers showed that jogging was associated with significantly lower all-cause mortality and a substantial increase in survival for both men and women.", "Light activities (<4 multiples of resting metabolic rate (METs)) were not associated with reduced mortality rates, moderate activities (4-<6 METs) appeared somewhat beneficial, and vigorous activities (> or =6 METs) clearly predicted lower mortality rates (p, trend = 0.72, 0.07, and <0.001, respectively).", "These data demonstrate a graded inverse relationship between total physical activity and mortality. Furthermore, vigorous activities but not nonvigorous activities were associated with longevity.", "The capacity for prolonged and vigorous physical exercise, particularly if the exercise is recreational, is a strong indicator of longevity." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/23449779", "http://www.ncbi.nlm.nih.gov/pubmed/7707624", "http://www.ncbi.nlm.nih.gov/pubmed/22587716", "http://www.ncbi.nlm.nih.gov/pubmed/21618162", "http://www.ncbi.nlm.nih.gov/pubmed/2279154", "http://www.ncbi.nlm.nih.gov/pubmed/10670554" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D008136", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D015444", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005082", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005081" ]

[ "Evolutionary processes create both newly derived characteristics shared by related descendant lineages (homology) and \"false\" similarities which confound phylogenetic reconstruction (homoplasy). Homology arises by divergent evolution from a common ancestor and provides us with a phylogenetic signal, while homoplasy arises by convergent evolution or random coincidence. Homoplastic characters do not allows branch points and clade membership to be accurately estimated, as they may group unrelated taxa together. Such characters add \"noise\" in phylogenetic analysis and are not informative for the population genetics and the phylogenetic reconstruction of closely related taxa. In phylogenetic reconstruction, homoplasy leads to inaccurate conclusions about phylogenetic relationships among operational taxonomic units, and characters with high degree of homoplasy result in incongruences of cladistic relationships." ]

[]

[ "Phylogenetic reconstruction using molecular data is often subject to homoplasy, leading to inaccurate conclusions about phylogenetic relationships among operational taxonomic units.", "Our use of nonhomoplastic whole-genome SNP characters allows branch points and clade membership to be estimated with great precision", "The control region proved to be a less useful molecular marker for the population genetics and the phylogenetic reconstruction of closely related taxa in A. urticae than it has for other species. The extreme bias in adenine and thymine content (A+T=90.91%) probably renders this region highly susceptible to homoplasy, resulting in a less informative molecular marker.", "Minimal homoplasy (consistency index = 0.9591) was detected among parsimony-informative SNPs, allowing for the generation of a highly accurate phylogenetic reconstruction of the CC398 clonal lineage.", "These findings provide evidence for the occurrence of a high degree of homoplasy in the DR locus leading to convergent evolution to identical spoligotypes. The incongruence between Large Sequence Polymorphism and spoligotype polymorphism argues against the use of spoligotyping for establishing phylogenetic relationships within the Euro-American lineage.", "The species diversity of the phylum Rotifera has been largely studied on the basis of morphological characters. However, cladistic relationships within this group are poorly resolved due to extensive homoplasy in morphological traits", "Molecular evolutionary processes modify DNA over time, creating both newly derived substitutions shared by related descendant lineages (phylogenetic signal) and \"false\" similarities which confound phylogenetic reconstruction (homoplasy).", "This added level of homoplasic \"noise\" can make DNA regions with repeats less reliable in phylogenetic reconstruction than those without repeats.", "Computational and phylogenetic analyses suggest that only some BH3 motifs arose by divergent evolution from a common ancestor (homology), whereas others arose by convergent evolution or random coincidence (homoplasy)", "The high frequency of morphological homoplasy in pennatulaceans has led to many misinterpretations in the systematics of the group.", "Conflict among data sources can be frequent in evolutionary biology, especially in cases where one character set poses limitations to resolution. Earthworm taxonomy, for example, remains a challenge because of the limited number of morphological characters taxonomically valuable. An explanation to this may be morphological convergence due to adaptation to a homogeneous habitat, resulting in high degrees of homoplasy. This sometimes impedes clear morphological diagnosis of species.", "We also report one of the first findings of homoplasy in mitochondrial gene order, namely a shared relative position of trnV in unrelated isopod lineages.", "This taxon therefore provides the opportunity to evaluate those neural characters common to these two clades likely to be results of shared ancestry (homology) versus convergence (homoplasy). ", "Taxa that experienced molecular homoplasy, recent selection, a spur of evolution, and so forth may disrupt the inference and cause incongruences in the estimated phylogeny.", "myrmecophagy in these mammalian lineages was more likely because of homoplasy (convergent evolution) than being an ancestral character.", "The four regions were equally affected by homoplasy and were, therefore, equally unreliable for phylogenetic reconstruction.", "Early hominid masticatory characters are widely considered to be more prone to homoplasy than characters from other regions of the early hominid skull and therefore less reliable for phylogenetic reconstruction.", "These findings are in clear contrast with the views that rapidly evolving regions and the 3rd codon position have inevitable negative impact on phylogenetic reconstruction at deep historic level due to accumulation of multiple hits and subsequent elevation in homoplasy and saturation.", "Phylogenetic reconstructions are often plagued by difficulties in distinguishing phylogenetic signal (due to shared ancestry) from phylogenetic noise or homoplasy (due to character-state convergences or reversals).", "Homoplasy, in particular, is a difficulty faced by all methods of phylogenetic inference.", "Homoplasy, in particular, is a difficulty faced by all methods of phylogenetic inference.", "Sequence-based methods for phylogenetic reconstruction from (nucleic acid) sequence data are notoriously plagued by two effects: homoplasies and alignment errors", "Early hominid masticatory characters are widely considered to be more prone to homoplasy than characters from other regions of the early hominid skull and therefore less reliable for phylogenetic reconstruction", "Molecular evolutionary processes modify DNA over time, creating both newly derived substitutions shared by related descendant lineages (phylogenetic signal) and \"false\" similarities which confound phylogenetic reconstruction (homoplasy)", "The four regions were equally affected by homoplasy and were, therefore, equally unreliable for phylogenetic reconstruction", "mellifera that the detection of size homoplasy may alter phylogenetic reconstructions." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/8042708", "http://www.ncbi.nlm.nih.gov/pubmed/21619604", "http://www.ncbi.nlm.nih.gov/pubmed/22728915", "http://www.ncbi.nlm.nih.gov/pubmed/15062799", "http://www.ncbi.nlm.nih.gov/pubmed/12116430", "http://www.ncbi.nlm.nih.gov/pubmed/22192390", "http://www.ncbi.nlm.nih.gov/pubmed/14530127", "http://www.ncbi.nlm.nih.gov/pubmed/22354957", "http://www.ncbi.nlm.nih.gov/pubmed/22491068", "http://www.ncbi.nlm.nih.gov/pubmed/9664695", "http://www.ncbi.nlm.nih.gov/pubmed/18577231", "http://www.ncbi.nlm.nih.gov/pubmed/18787123", "http://www.ncbi.nlm.nih.gov/pubmed/22228800", "http://www.ncbi.nlm.nih.gov/pubmed/15347815", "http://www.ncbi.nlm.nih.gov/pubmed/22431149", "http://www.ncbi.nlm.nih.gov/pubmed/20525577", "http://www.ncbi.nlm.nih.gov/pubmed/11098408", "http://www.ncbi.nlm.nih.gov/pubmed/16414286", "http://www.ncbi.nlm.nih.gov/pubmed/23906600", "http://www.ncbi.nlm.nih.gov/pubmed/11534998", "http://www.ncbi.nlm.nih.gov/pubmed/2682738", "http://www.ncbi.nlm.nih.gov/pubmed/10605118", "http://www.ncbi.nlm.nih.gov/pubmed/24932884", "http://www.ncbi.nlm.nih.gov/pubmed/23199982", "http://www.ncbi.nlm.nih.gov/pubmed/23378793", "http://www.ncbi.nlm.nih.gov/pubmed/15805007" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D058974" ]

[ "Greater risk for autism spectrum disorders has been reported among mothers that have used selective serotonin reuptake inhibitors during pregnancy. However, others did not find an association between the use of selective serotonin reuptake inhibitors during pregnancy and risk for autism in offspring. Also, selective serotonin reuptake inhibitor use during pregnancy were associated with a greater number of gastrointestinal complaints in children with autism spectrum disorders." ]

[]

[ "In doing so, we examined whether two proposed risk factors - low birth weight (LBW), and in utero exposure to selective serotonin reuptake inhibitors (SSRIs) - are associated with greater behavioral homogeneity. Using data from the Western Australian Autism Biological Registry, this study found that LBW and maternal SSRI use during pregnancy were associated with greater sleep disturbances and a greater number of gastrointestinal complaints in children with ASD, respectively.", "The outcome of one study suggested that children with autism were more likely to have a mother who was prescribed an SSRI during pregnancy.", "A history of maternal (adjusted odds ratio 1.49, 95% confidence interval 1.08 to 2.08) but not paternal depression was associated with an increased risk of autism spectrum disorders in offspring. In the subsample with available data on drugs, this association was confined to women reporting antidepressant use during pregnancy (3.34, 1.50 to 7.47, P=0.003), irrespective of whether selective serotonin reuptake inhibitors (SSRIs) or non-selective monoamine reuptake inhibitors were reported.", "In utero exposure to both SSRIs and non-selective monoamine reuptake inhibitors (tricyclic antidepressants) was associated with an increased risk of autism spectrum disorders, particularly without intellectual disability.", "Repeated findings of elevated platelet serotonin levels in approximately one third of children with autism has led some to believe that dysfunctional serotonin signaling may be a causal mechanism for the disorder. Because serotonin is critical to fetal brain development, concerns have arisen regarding prenatal exposure to substances that manipulate serotonin levels, such as selective serotonin reuptake inhibitors (SSRIs).", "Though the majority of studies conducted in infants and children suggest prenatal exposure to SSRIs does not affect neurodevelopment, interpretation must be tempered given small sample sizes. The only published study that focused on prenatal SSRI exposure and ASD found an increased risk with exposure to SSRIs, especially during the first trimester. ", "Among the potential environmental factors, hyperserotonemia during pregnancy and its effect on brain development could be playing a role in this prevalence raise. In the rodent model developed by Whitaker-Azmitia and colleagues, hyperserotonemia during fetal development results in a dysfunction of the hypothalamo-pituitary axis, affecting the amygdala as well as pro-social hormone oxytocin regulation. Dysfunction of the amygdala and abnormal oxytocin levels may underlie many clinical features of ASD. Selective serotonin reuptake inhibitors (SSRI) are the most widely used class of antidepressants drugs, and they are not contraindicated during pregnancy. ", "In adjusted logistic regression models, we found a 2-fold increased risk of ASD associated with treatment with selective serotonin reuptake inhibitors by the mother during the year before delivery (adjusted odds ratio, 2.2 [95% confidence interval, 1.2-4.3]), with the strongest effect associated with treatment during the first trimester (adjusted odds ratio, 3.8 [95% confidence interval, 1.8-7.8]).", "Although the number of children exposed prenatally to selective serotonin reuptake inhibitors in this population was low, results suggest that exposure, especially during the first trimester, may modestly increase the risk of ASD. ", "Together, these results indicate that administration of SSRIs during a sensitive period of brain development results in long-lasting alterations in NE-LC circuit function in adults and may be useful in understanding the etiology of pervasive developmental disorders such as autism spectrum disorder.", " Although several studies have not confirmed an increased risk for adverse neurodevelopment, a recent study observed an increased risk for autism spectrum disorders in prenatally exposed offspring. ", "Considering the important role of serotonin in central nervous system development, more studies are needed to assess the possible adverse effects on long-term neurodevelopment." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/24065914", "http://www.ncbi.nlm.nih.gov/pubmed/21727247", "http://www.ncbi.nlm.nih.gov/pubmed/23681158", "http://www.ncbi.nlm.nih.gov/pubmed/23604083", "http://www.ncbi.nlm.nih.gov/pubmed/20018455", "http://www.ncbi.nlm.nih.gov/pubmed/22090498", "http://www.ncbi.nlm.nih.gov/pubmed/23495208", "http://www.ncbi.nlm.nih.gov/pubmed/23042258" ]

[]

[ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0007565", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D017367", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001321", "http://www.disease-ontology.org/api/metadata/DOID:12849", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011247", "http://www.disease-ontology.org/api/metadata/DOID:0060041" ]

[ "Downregulation of E-cadherin is a crucial event for epithelial to mesenchymal transition (EMT) in embryonic development and cancer progression. Overexpression of Snail1 (Snail), Snail2 (Slug), Zeb1, Twist, SIP1 and DeltaEF1 have been found to mediate E-cadherin repression, induce the mesenchymal markers vimentin and fibronectin, and finally promote the migratory and invasive capabilities in cancer cells." ]

[ "Snail1 (Snail)", "Snail2 (Slug)", "Zeb1", "Twist", "SIP1", "DeltaEF1" ]

[ "ifferential role of Snail1 and Snail2 zinc fingers in E-cadherin repression and epithelial to mesenchymal transition", "nail1 (Snail) and Snail2 (Slug) are transcription factors that share a similar DNA binding structure of four and five C2H2 zinc finger motifs (ZF), respectively. Both factors bind specifically to a subset of E-box motifs (E2-box: CAGGTG/CACCTG) in target promoters like the E-cadherin promoter and are key mediators of epithelial-to-mesenchymal transition (EMT).", "hrombin induces slug-mediated E-cadherin transcriptional repression and the parallel up-regulation of N-cadherin by a transcription-independent mechanism in RPE cells", "We demonstrate, for the first time, that thrombin induces E-cadherin repression by stimulating snail-2 (SLUG) transcription factor expression,", "Mutation of the putative GSK-3β phosphorylation sites (S92/96A or S100/104A) enhanced the Slug/Snail2-mediated EMT properties of E-cadherin repression and vimentin induction, compared with wild-type Slug/Snail2.", "xpression of E-cadherin, a hallmark of epithelial-mesenchymal transition (EMT), is often lost due to promoter DNA methylation in basal-like breast cancer (BLBC),", "Here, we identified that Snail interacted with Suv39H1 (suppressor of variegation 3-9 homolog 1), a major methyltransferase responsible for H3K9me3 that intimately links to DNA methylation. ", "We showed that Snail interacted with Suv39H1 and recruited it to the E-cadherin promoter for transcriptional repression.", "Knockdown of Suv39H1 restored E-cadherin expression by blocking H3K9me3 and DNA methylation and resulted in the inhibition of cell migration, invasion and metastasis of BLBC.", "9a interacts with Snail and is critical for Snail-mediated E-cadherin repression in human breast cancer", "Here, we have determined that methylation of histone H3 on lysine 9 (H3K9me2) is critical for promoter DNA methylation of E-cadherin in three TGF-β-induced EMT model cell lines, as well as in CLBC cell lines.", "Further, Snail interacted with G9a, a major euchromatin methyltransferase responsible for H3K9me2, and recruited G9a and DNA methyltransferases to the E-cadherin promoter for DNA methylation.", "Knockdown of G9a restored E-cadherin expression by suppressing H3K9me2 and blocking DNA methylation. This resulted in inhibition of cell migration and invasion in vitro and suppression of tumor growth and lung colonization in in vivo models of CLBC metastasis.", "ZEB1, which targets E-cadherin repression, is a transcriptional regulator that has been implicated in EMT, and is associated with uterine and colorectal cancers.", "The introduction or knockdown of ZEB1 expression in bladder carcinoma cell lines showed enhanced or reduced migration and invasive potential, respectively.", "However, in vitro assays showed enhanced or reduced migration and invasion after the introduction or reduction of ZEB1, respectively, in transfected bladder cell lines.", "Finally, we showed aberrant IL-6 production and STAT3 activation in MCF-7 cells that constitutively express Twist, a metastatic regulator and direct transcriptional repressor of E-cadherin. To our knowledge, this is the first study that shows IL-6 as an inducer of an EMT phenotype in breast cancer cells and implicates its potential to promote breast cancer metastasis.", "unctional loss of the cell-cell adhesion molecule E-cadherin is an essential event for epithelial-mesenchymal transition (EMT), a process that allows cell migration during embryonic development and tumour invasion. In most carcinomas, transcriptional repression has emerged as the main mechanism responsible for E-cadherin downregulation.", "Here, we report the identification of class I bHLH factor E2-2 (TCF4/ITF2) as a new EMT regulator.", "E-cadherin repression mediated by E2-2 is indirect and independent of proximal E-boxes of the promoter.", "Knockdown studies indicate that E2-2 expression is dispensable for maintenance of the EMT driven by Snail1 and E47.", "Slug mRNA was shown to be over-expressed in adenocarcinoma and inversely correlated to E-cadherin expression.", "Overexpression of Slug in OE33 mediated E-cadherin repression and induced the mesenchymal markers vimentin and fibronectin.", "SIP1 and deltaEF1 each dramatically down-regulated the transcription of E-cadherin in NMuMG cells through direct binding to the E-cadherin promoter.", "Silencing of the expression of both SIP1 and deltaEF1, but not either alone, completely abolished TGF-beta-induced E-cadherin repression.", "eltaEF1 is a transcriptional repressor of E-cadherin and regulates epithelial plasticity in breast cancer cells", "ownregulation of E-cadherin is a crucial event for epithelial to mesenchymal transition (EMT) in embryonic development and cancer progression.", "Using the EpFosER mammary tumour model we show that during EMT, upregulation of the transcriptional regulator deltaEF1 coincided with transcriptional repression of E-cadherin.", "Ectopic expression of deltaEF1 in epithelial cells was sufficient to downregulate E-cadherin and to induce EMT.", "Analysis of E-cadherin promoter activity and chromatin immunoprecipitation identified deltaEF1 as direct transcriptional repressor of E-cadherin.", "In human cancer cells, transcript levels of deltaEF1 correlated directly with the extent of E-cadherin repression and loss of the epithelial phenotype.", "RNA interference-mediated downregulation of deltaEF1 in cancer cells was sufficient to derepress E-cadherin expression and restore cell to cell adhesion, suggesting that deltaEF1 is a key player in late stage carcinogenesis.", "TGF-beta-induced the expression of Ets1, which in turn activated deltaEF1 promoter activity. Moreover, up-regulation of SIP1 and deltaEF1 expression by TGF-beta was suppressed by knockdown of Ets1 expression. ", "ETV5 modulated Zeb1 expression and E-Cadherin repression leading to a complete reorganization of cell-cell and cell-substrate contacts. ETV5-promoted EMT resulted in the acquisition of migratory and invasive capabilities in endometrial cell lines." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/19581928", "http://www.ncbi.nlm.nih.gov/pubmed/22833386", "http://www.ncbi.nlm.nih.gov/pubmed/19295128", "http://www.ncbi.nlm.nih.gov/pubmed/22727060", "http://www.ncbi.nlm.nih.gov/pubmed/22562246", "http://www.ncbi.nlm.nih.gov/pubmed/15674322", "http://www.ncbi.nlm.nih.gov/pubmed/22406531", "http://www.ncbi.nlm.nih.gov/pubmed/20735391", "http://www.ncbi.nlm.nih.gov/pubmed/22266854", "http://www.ncbi.nlm.nih.gov/pubmed/17615296", "http://www.ncbi.nlm.nih.gov/pubmed/18286686", "http://www.ncbi.nlm.nih.gov/pubmed/24297167" ]

[]

[ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0001837", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D015820", "http://www.uniprot.org/uniprot/CADH1_HUMAN", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D058750", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D014157", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0060231" ]

[ "According to the predominant view, desmin mutations cause dilated cardiomyopathy (DCM). Mice deficient in desmin, the muscle-specific member of the intermediate filament gene family, display defects in all muscle types and particularly in the myocardium. Desmin null hearts develop cardiomyocyte hypertrophy and dilated cardiomyopathy (DCM) characterized by extensive myocyte cell death, calcific fibrosis and multiple ultrastructural defects. Desmin defects were also recently identified in 1 familial dilated cardiomyopathy." ]

[ "yes" ]

[ "Desmin-related myofibrillar myopathy (DRM) is a cardiac and skeletal muscle disease caused by mutations in the desmin (DES) gene. Mutations in the central 2B domain of DES cause skeletal muscle disease that typically precedes cardiac involvement. However, the prevalence of DES mutations in dilated cardiomyopathy (DCM) without skeletal muscle disease is not known.", "The lack of severe disruption of cytoskeletal desmin network formation seen with mutations in the 1A and tail domains suggests that dysfunction of seemingly intact desmin networks is sufficient to cause DCM.", "According to the predominant view, desmin mutations cause dilated cardiomyopathy (DCM). We evaluated a family with restrictive cardiomyopathy (RCM) associated with a novel desmin mutation and reviewed recent reports regarding the frequency of RCM in patients with desmin myopathy.", "Dilated cardiomyopathy (DCM) is characterized by enlargement and dilation of all heart compartments associated with serious decrease of its contractile function. DCM hallmark is the combination of dystrophic and hypertrophic alterations of cardiomyocytes. Since the power output of cardiac cells is directly related to remodeling of their contractile machinery we investigated expression of selected contractile and cytoskeletal proteins in the left ventricle of DCM patients using immunoblotting. The content of the recognized protein markers of cardiomyocyte hypertrophy such as tubulin, desmin and slow skeletal myosin heavy chain isoform, MHCbeta, was significantly elevated in DCM compared to normal myocardium.", "In contrast, overexpression of desmin filaments by itself is not detrimental to the heart. Although loss-of-function studies have been more limited, ablation of the desmin gene causes mitochondrial dysfunction and apoptosis, resulting in cardiomyopathy in mice. From function studies, abnormal desmin aggregation and disruption of the desmin networks resulting from expression of either mutant desmin or mutant CryAB have been shown to remodel the heart and compromise cardiac function, suggesting their synergistic roles in disease pathogenesis.", "A missense mutation in the desmin gene (DES) causes DCM in a human family.", "Mice deficient in desmin, the muscle-specific member of the intermediate filament gene family, display defects in all muscle types and particularly in the myocardium. Desmin null hearts develop cardiomyocyte hypertrophy and dilated cardiomyopathy (DCM) characterized by extensive myocyte cell death, calcific fibrosis and multiple ultrastructural defects. Several lines of evidence suggest impaired vascular function in desmin null animals.", "Familial DCM is commonly inherited as autosomal dominant trait; less frequently it is autosomal recessive, X-linked or matrilinear. The disease is clinically and genetically heterogeneous. Genes causally linked to this phenotype include dystrophin, dystrophin-associated glycoproteins, actin, desmin, beta-miosin heavy chain, cardiac troponin T, and mitochondrial DNA genes, mostly transfer RNAs.", "Examination of families has identified so far eight disease genes, namely the dystrophin, tafazzin, cardiac actin, desmin, lamin A/C, delta- sarcoglycan, cardiac beta-myosin heavy chain, and cardiac troponin T gene.", "Mutations of the desmin, delta-sarcoglycan, the cardiac actin and beta-myosin heavy chain as well as the troponin T gene are known to cause autosomal dominant-dilated cardiomyopathy without other abnormalities.", "Autosomal dominant DCM is the most frequent form (56% of our cases), and several candidate disease loci have been identified by linkage analysis. Three disease genes are presently known: the cardiac actin gene, the desmin gene, and the lamin A/C gene.", "Dilated cardiomyopathy (DCM) is a major cause of morbidity and mortality. Two genes have been identified for the X-linked forms (dystrophin and tafazzin), whereas three other genes (actin, lamin A/C, and desmin) cause autosomal dominant DCM;", "Desmin defects were also recently identified in 1 familial dilated cardiomyopathy.", "By candidate gene screening, the molecular diagnosis can be provided for dystrophin, DAG, mitochondrial DNA, actin and desmin gene defects.", "Desmin (z-bands) are partly destroyed in DCM. Anti-desmin antibody titers as indicators of a possible secondary immune response are found high in patients with acute myocarditis declining during reconvalescence and are also elevated in DCM. ", "Desmin, the muscle-specific intermediate filament protein, is a major target in dilated cardiomyopathy and heart failure in humans and mice", "Desmin, the muscle-specific intermediate filament, is involved in myofibrillar myopathies, dilated cardiomyopathy and muscle wasting" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/10904833", "http://www.ncbi.nlm.nih.gov/pubmed/15475165", "http://www.ncbi.nlm.nih.gov/pubmed/16890305", "http://www.ncbi.nlm.nih.gov/pubmed/15699919", "http://www.ncbi.nlm.nih.gov/pubmed/14734054", "http://www.ncbi.nlm.nih.gov/pubmed/10974018", "http://www.ncbi.nlm.nih.gov/pubmed/17325244", "http://www.ncbi.nlm.nih.gov/pubmed/11374497", "http://www.ncbi.nlm.nih.gov/pubmed/7774871", "http://www.ncbi.nlm.nih.gov/pubmed/12025381", "http://www.ncbi.nlm.nih.gov/pubmed/15572040", "http://www.ncbi.nlm.nih.gov/pubmed/24091796", "http://www.ncbi.nlm.nih.gov/pubmed/11515275", "http://www.ncbi.nlm.nih.gov/pubmed/21525025" ]

[]

[ "http://www.uniprot.org/uniprot/DESM_RAT", "http://www.uniprot.org/uniprot/DESM_HUMAN", "http://www.uniprot.org/uniprot/DESM_CHICK", "http://www.uniprot.org/uniprot/DESM_MOUSE", "http://www.uniprot.org/uniprot/DESM_XENLA", "http://www.disease-ontology.org/api/metadata/DOID:12930", "http://www.uniprot.org/uniprot/DESM_CANFA", "http://www.uniprot.org/uniprot/DESM_PIG", "http://www.uniprot.org/uniprot/DESM_MESAU" ]

[ "Lambrolizumab, a programmed death-1 receptor (PD-1)/its ligand (PD-L1) antibody, has been shown to be effective for treatment of patients with melanoma. High rate of sustained tumor regression with mainly minimal adverse effects in melanoma patients treated with lambrolizumab has been reported. Because of all these reasons PD-1/PD-L1 antibodies are considered 'drug of the year.", "Yes. In patients with advanced melanoma, including those who had had disease progression while they had been receiving ipilimumab, treatment with lambrolizumab resulted in a high rate of sustained tumor regression, with mainly grade 1 or 2 toxic effects." ]

[ "yes" ]

[ "However, through parallel efforts that have showcased the efficacy of small-molecule BRAF and MAP-ERK kinase (MEK) inhibitors, as well as the immune checkpoint inhibitors, namely ipilimumab and the anti-PD1/PDL1 antibodies (lambrolizumab, nivolumab, MPDL3280), an opportunity exists to transform the treatment of melanoma specifically and cancer generally by exploring rational combinations of molecularly targeted therapies, immunotherapies, and molecular targeted therapies with immunotherapies. ", "Programmed death-1 receptor (PD-1)/its ligand (PD-L1) antibodies have changed the landscape in oncology in 2013. The most mature results have been obtained in advanced melanoma patients. ", "Merck's lambrolizumab (MK-3475) monoclonal antibody received \"Breakthrough Therapy\" designation from the U.S. Food and Drug Administration in April for treating patients with advanced melanoma.", "The programmed death 1 (PD-1) receptor is a negative regulator of T-cell effector mechanisms that limits immune responses against cancer. We tested the anti-PD-1 antibody lambrolizumab (previously known as MK-3475) in patients with advanced melanoma. ", "In patients with advanced melanoma, including those who had had disease progression while they had been receiving ipilimumab, treatment with lambrolizumab resulted in a high rate of sustained tumor regression, with mainly grade 1 or 2 toxic effects. ", "Because of all these reasons PD-1/PD-L1 antibodies are considered 'drug of the year'." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/23724846", "http://www.ncbi.nlm.nih.gov/pubmed/24416617", "http://www.ncbi.nlm.nih.gov/pubmed/23847357", "http://www.ncbi.nlm.nih.gov/pubmed/24089441", "http://www.ncbi.nlm.nih.gov/pubmed/24499550", "http://www.ncbi.nlm.nih.gov/pubmed/23970885", "http://www.ncbi.nlm.nih.gov/pubmed/24516336", "http://www.ncbi.nlm.nih.gov/pubmed/23907003", "http://www.ncbi.nlm.nih.gov/pubmed/24348481", "http://www.ncbi.nlm.nih.gov/pubmed/23997828" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D018328", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013812", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D018326", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016896", "http://www.disease-ontology.org/api/metadata/DOID:1909", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D008545" ]

[ "Prader Willi Syndrome\nAngelman syndrome\nBeckwith-Wiedemann syndrome\nHydatidiform mole\nCancer\nSilver-Russell syndrome\nDiabetes" ]

[ "Prader Willi Syndrome", "Angelman syndrome", "Beckwith-Wiedemann syndrome", "Hydatidiform mole", "Cancer", "Silver-Russell syndrome", "Diabetes" ]

[ " Here we describe the clinical case of a female patient with Prader Willi Syndrome (PWS), a genomic imprinting disorder", "Perturbation of the allelic DNA methylation at ICRs is causally involved in several human diseases, including the Beckwith-Wiedemann and Silver-Russell syndromes, associated with aberrant foetal growth.", "Perturbed imprinted gene expression is also implicated in the neuro-developmental disorders Prader-Willi syndrome and Angelman syndrome.", "This epigenetic \"life cycle\" of imprinting (germline erasure, germline establishment, and somatic maintenance) can be disrupted in several human diseases, including Beckwith-Wiedemann syndrome (BWS), Prader-Willi syndrome (PWS), Angelman syndrome and Hydatidiform mole.", "In the neurodevelopmental Rett syndrome, the way the ICR mediates imprinted expression is perturbed.", "eregulation of imprinted genes has been observed in a number of human diseases as gestation trophoblastic disease, Prader-Willi, Angelmann and Beckwith-Wiedemann syndromes and plays significant role in the carcinogenesis.", "Angelman's syndrome families, which are known to be imprinted. ", "Deregulation of imprinted genes has been observed in a number of human diseases such as Beckwith-Wiedemann syndrome, Prader-Willi/Angelman syndromes and cancer.", "Genomic imprinting is the phenomenon whereby some genes preferentially produce mRNA transcripts from the gene copy derived from the parent of a specific sex. It has been implicated in a number of human diseases (most of them of endocrine interest), such as Prader-Willi/Angelman syndromes, Silver-Russell syndrome, Beckwith-Wiedemann syndrome, transient neonatal diabetes, the focal form of nesidioblastosis, and pseudohypoparathyroidism.", "imprinting disorders like Beckwith-Wiedemann and Prader-Willi/Angelman syndromes", "It is particularly interesting from the clinical point of view that a number of human diseases, such as the Beckwith-Wiedemann and Prader-Willi/Angelman syndromes, appear to involve unbalanced parental contributions of imprinted loci. ", "Examples include the Prader-Willi, Angelman, and Beckwith-Wiedemann syndromes [Nicholls (1994): Am J Hum Genet 54:733-740], malignancy [Sapienza (1990): Biochim Biophys Acta 1072:51-61; Feinberg (1993): Nat Genet 4:110-113], and insulin-dependent diabetes mellitus (IDDM) [Julier et al. (1994) Nature 354:155-159; Bennett et al. (1995) Nat Genet 9:284-292]. " ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/15945483", "http://www.ncbi.nlm.nih.gov/pubmed/22960339", "http://www.ncbi.nlm.nih.gov/pubmed/12524013", "http://www.ncbi.nlm.nih.gov/pubmed/12444886", "http://www.ncbi.nlm.nih.gov/pubmed/16035043", "http://www.ncbi.nlm.nih.gov/pubmed/7868070", "http://www.ncbi.nlm.nih.gov/pubmed/15802919", "http://www.ncbi.nlm.nih.gov/pubmed/11568896", "http://www.ncbi.nlm.nih.gov/pubmed/20822494", "http://www.ncbi.nlm.nih.gov/pubmed/8565331" ]

[]

[ "http://www.disease-ontology.org/api/metadata/DOID:4", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D015894", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:2000653", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D018392", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0071514", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016678" ]

[ "a) They inhibit oncogene activation upon vector integration and b) They maximize the probability of vector expression upon integration in heterochromatinic regions", "The presence of insulators in gene therapy vectors is necessary because these elements have the ability to help overcome the problem of position effects, caused due to random integration of the therapeutic genes in the host cell genome." ]

[]

[ "hromatin insulators separate active transcriptional domains and block the spread of heterochromatin in the genome. Studies on the chicken hypersensitive site-4 (cHS4) element, a prototypic insulator, have identified CTCF and USF-1/2 motifs in the proximal 250 bp of cHS4, termed the \"core\", which provide enhancer blocking activity and reduce position effects.", "An attractive solution to the problem of oncogene activation is the inclusion of insulators/enhancer-blockers in the viral vectors.", "We propose the incorporation of chromatin insulators in the design of gene therapy vectors to overcome the problem of position effects. Chromatin insulators are protein-binding DNA elements that lack intrinsic promoter/enhancer activity but shelter genes from transcriptional influence of surrounding chromatin.", "The design and incorporation of effective chromatin insulator sequences in the next generation of gene therapy vectors should lead to improved and more predictable expression of therapeutic transgenes and constitute an important step toward clinically effective gene therapy." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/21562592", "http://www.ncbi.nlm.nih.gov/pubmed/21205311", "http://www.ncbi.nlm.nih.gov/pubmed/21475904", "http://www.ncbi.nlm.nih.gov/pubmed/19352322", "http://www.ncbi.nlm.nih.gov/pubmed/12200360", "http://www.ncbi.nlm.nih.gov/pubmed/24098520", "http://www.ncbi.nlm.nih.gov/pubmed/9368350", "http://www.ncbi.nlm.nih.gov/pubmed/24312663", "http://www.ncbi.nlm.nih.gov/pubmed/19746166", "http://www.ncbi.nlm.nih.gov/pubmed/21247248", "http://www.ncbi.nlm.nih.gov/pubmed/14683449", "http://www.ncbi.nlm.nih.gov/pubmed/23786330", "http://www.ncbi.nlm.nih.gov/pubmed/15638709", "http://www.ncbi.nlm.nih.gov/pubmed/19536296" ]

[ { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A11616828", "o": "GO:0043035" }, { "p": "http://www.w3.org/2008/05/skos-xl#prefLabel", "s": "http://linkedlifedata.com/resource/umls/id/C1156211", "o": "http://linkedlifedata.com/resource/umls/label/A11616828" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A11616828", "o": "chromatin insulator sequence binding" } ]

[ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0044009", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0044008", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D002273", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D038101", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0010468", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005796", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0043035", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0010629", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D015316", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0016458", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0045892", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0010628", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0045893", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009857", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0006355", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005822", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0010467", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004199", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D015513" ]

[ "It has been well-documented that iron deficiency is the cause of restless leg syndrome. Magnesium and ferritin were also associated with restless leg syndrome." ]

[ "iron" ]

[ "We describe a unique case of a 23-yr-old female patient affected by a homozygous loss of function mutation in the L-ferritin gene, idiopathic generalized seizures, and atypical restless leg syndrome (RLS). We show that L chain ferritin is undetectable in primary fibroblasts from the patient, and thus ferritin consists only of H chains.", "Our results demonstrate for the first time the pathophysiological consequences of L-ferritin deficiency in a human and help to define the concept for a new disease entity hallmarked by idiopathic generalized seizure and atypical RLS.", "These results when viewed along with prior RLS SPECT and autopsy studies of DAT, and cell culture studies with iron deficiency and DAT, suggest that membrane-bound striatal DAT, but not total cellular DAT, may be decreased in RLS.", " Compared with the PD or healthy group, the level of serum ferritin and the H-reflex latency of tibial nerve were significantly decreased in PD with RLS group (P < 0.05).", "Deficiency of iron and decreased inhibition function of spinal cord may lead to the occurrence of RLS in PD patients. ", "Association of iron deficiency with febrile seizures, pica, breath holding spells, restless leg syndrome and thrombosis is increasingly being recognized.", " Iron status was generally poor among regular blood donors, especially in women, with a high incidence of iron depletion (>20%) and RLS (18%). ", "Iron status is poor in regular blood donors, restless legs syndrome is common, and the routine iron supplementation is insufficient. ", "Furthermore, there appears to be an association between iron deficiency and those suffering from Restless Leg Syndrome (RLS). ", "The authors propose that PPIs, such as omeprazole, may interfere with iron absorption in certain patients and that a subpopulation of patients who develop significant iron deficiency characterized by low serum ferritin levels while on PPIs may also develop RLS-like symptoms (including RLSAP).", "Clinical studies have implicated the dopaminergic system in RLS, while others have suggested that it is associated with insufficient levels of brain iron. ", "The results are consistent with the hypothesis that a primary iron insufficiency produces a dopaminergic abnormality characterized as an overly activated dopaminergic system as part of the RLS pathology.", "RLS may also be secondary to a number of conditions including iron deficiency, pregnancy and end-stage renal failure and, perhaps, neuropathy.", "The pathogenesis of RLS probably involves the interplay of systemic or brain iron deficiency and impaired dopaminergic neurotransmission in the subcortex of the brain. ", "All patients showed low levels of ferritin and iron supplementation was effective in five cases. ", "Clinical and animal studies that support the benefits of iron supplementation, independent of increasing hemoglobin, such as those on immune function, physical performance, thermoregulation, cognition, and restless leg syndrome and aluminum absorption is the subject of this narrative review.", "Restless leg syndrome (RLS) and periodic limb movement disorder (PLMD) are considered to be a continuum of a neurological sleep disorder associated with abnormal iron metabolism or deficiency. I describe a case of RLS and PLMD in a cystic fibrosis patient with iron deficiency from chronic hemoptysis. This is the first case that reports RLS and PLMD manifesting from iron deficiency caused by chronic hemoptysis in advanced cystic fibrosis lung disease.", "Restless leg syndrome manifested by iron deficiency from chronic hemoptysis in cystic fibrosis.", "Diurnal effects on motor control are evident in the human disease of Restless Leg Syndrome (RLS), which is purported to be linked to brain iron deficiency as well as alterations in dopaminergic systems. ", "Iron deficiency in the central nervous system is known to cause motor impairment and cognitive deficits; more recently, it has been suggested that it may play a role in the pathophysiology of the restless leg syndrome. ", "Restless leg syndrome (RLS), aging, pregnancy, uraemia, iron deficiency, polyneuropathy are some of the common causes of secondary PLMD.", "The syndrome is increasingly often diagnosed, particularly in association with iron deficiency, during pregnancy, in chronic renal failure and in patients with peripheral neuropathy. ", "Clinical, EEG, electromyographic and polysomnographic studies in restless legs syndrome caused by magnesium deficiency.", "A frequent polymorphism in BTBD9 was significantly associated with serum ferritin. This polymorphism has previously been associated with RLS, but not low iron stores in blood donors." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/19935988", "http://www.ncbi.nlm.nih.gov/pubmed/11863398", "http://www.ncbi.nlm.nih.gov/pubmed/22258033", "http://www.ncbi.nlm.nih.gov/pubmed/21358851", "http://www.ncbi.nlm.nih.gov/pubmed/11310286", "http://www.ncbi.nlm.nih.gov/pubmed/11799409", "http://www.ncbi.nlm.nih.gov/pubmed/22377249", "http://www.ncbi.nlm.nih.gov/pubmed/20814842", "http://www.ncbi.nlm.nih.gov/pubmed/19039990", "http://www.ncbi.nlm.nih.gov/pubmed/24267148", "http://www.ncbi.nlm.nih.gov/pubmed/20303704", "http://www.ncbi.nlm.nih.gov/pubmed/22096645", "http://www.ncbi.nlm.nih.gov/pubmed/17804903", "http://www.ncbi.nlm.nih.gov/pubmed/21211209", "http://www.ncbi.nlm.nih.gov/pubmed/14643912", "http://www.ncbi.nlm.nih.gov/pubmed/18360657", "http://www.ncbi.nlm.nih.gov/pubmed/24101430", "http://www.ncbi.nlm.nih.gov/pubmed/23940258", "http://www.ncbi.nlm.nih.gov/pubmed/12530992", "http://www.ncbi.nlm.nih.gov/pubmed/21398376", "http://www.ncbi.nlm.nih.gov/pubmed/22486183", "http://www.ncbi.nlm.nih.gov/pubmed/19467991", "http://www.ncbi.nlm.nih.gov/pubmed/16982219", "http://www.ncbi.nlm.nih.gov/pubmed/21779527", "http://www.ncbi.nlm.nih.gov/pubmed/23257652", "http://www.ncbi.nlm.nih.gov/pubmed/16828857", "http://www.ncbi.nlm.nih.gov/pubmed/20598107" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D003677", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012148", "http://www.disease-ontology.org/api/metadata/DOID:0050425" ]

[ "Acetylated lysines in histones (generally H3 and H4)" ]

[ "Acetylated lysines" ]

[ "acetyllysine-specific protein-protein interaction with bromodomain reader modules", "Bromodomains bind acetylated lysines, acting as readers of the histone-acetylation code", " three acetyllysine ligands are indentified for a PHD-adjacent bromodomain in BPTF via systematic screening and biophysical characterization.", "acetyl-lysine binding bromodomain (BRD)", "bromodomain proteins bind to acetylated lysines in histones", "romodomains are present in many chromatin-associated proteins such as the SWI/SNF and RSC chromatin remodelling and the SAGA HAT (histone acetyltransferase) complexes, and can bind to acetylated lysine residues in the N-terminal tails of the histones", "recognition of acetylated histones by bromodomains", "BRD7, a novel bromodomain gene", "BRD7 interacted with H3 peptide acetylated", "bromodomain-containing proteins that recognize histone acetylation sites", "bromodomains of Gcn5, PCAF, TAF1 and CBP are able to recognize acetyllysine residues in histones", "romodomain factor 1 (Bdf1", " Bdf1 binds preferentially to acetylated histone H4", "chromatin remodeling complex RSC bears multiple bromodomains, motifs for acetyl-lysine and histone tail interaction", " in vitro binding of a HAT bromodomain with acetylated lysines within H3 and H4 amino-terminal peptides", "bromodomain, that recognizes acetylated residues" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/15014446", "http://www.ncbi.nlm.nih.gov/pubmed/21596426", "http://www.ncbi.nlm.nih.gov/pubmed/17049045", "http://www.ncbi.nlm.nih.gov/pubmed/21189220", "http://www.ncbi.nlm.nih.gov/pubmed/16265664", "http://www.ncbi.nlm.nih.gov/pubmed/10746732", "http://www.ncbi.nlm.nih.gov/pubmed/15382140", "http://www.ncbi.nlm.nih.gov/pubmed/15143168", "http://www.ncbi.nlm.nih.gov/pubmed/21851057", "http://www.ncbi.nlm.nih.gov/pubmed/15970672", "http://www.ncbi.nlm.nih.gov/pubmed/23095041", "http://www.ncbi.nlm.nih.gov/pubmed/21271695", "http://www.ncbi.nlm.nih.gov/pubmed/10716917" ]

[]

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

[ "Loss of memory and dysmnesia are memory problems reported in the \" Gulf war syndrome\". Patients suffering from this syndrome often have other\nnonspecific symptoms such as fatigue, skin rash, headache, muscle and joint pain and sexual dysfunction." ]

[ "loss of memory", "dysmnesia" ]

[ "The strongest associations were for mood swings (OR 20.9, 95%CI 16.2-27.0), memory loss/lack of concentration (OR 19.6, 95% CI 15.5-24.8), night sweats (OR 9.9, 95% CI 6.5-15.2), general fatigue (OR 9.6, 95% CI 8.3-11.1) and sexual dysfunction (OR 4.6, 95%CI 3.2-6.6).", "The symptoms include incapacitating fatigue, musculoskeletel and joint pains, headaches, neuropsychiatric disorders, affect changes, confusion, visual problems, changes of gait, loss of memory, lymphadenopathies, respiratory impairment, impotence, and urinary tract morphological and functional alterations. ", "In early 1992, U.S. troops returning from the Gulf War began reporting a variety of nonspecific symptoms such as fatigue, skin rash, headache, muscle and joint pain, and loss of memory. These reports marked the beginning of what was to be identified as the Gulf War Syndrome (GWS). ", "We report on a 29-year-old man who suffered from dysmnesia, disturbance of orientation, cognitive impairment, and double vision. His history revealed several front-line operations in 1990 and 1991 during the Gulf War. ", "Neuropsychological tests disclosed severe cognitive impairment especially concerning memory.", "A cluster of common health problems included: skin rash, cough, depression, unintentional weight loss, insomnia, and memory problems.", "Syndromes 1 (\"impaired cognition,\" characterized by problems with attention, memory, and reasoning, as well as insomnia, depression, daytime sleepiness, and headaches), 2 (\"confusion-ataxia,\" characterized by problems with thinking, disorientation, balance disturbances, vertigo, and impotence), and 3 (\"arthro-myo-neuropathy,\" characterized by joint and muscle pains, muscle fatigue, difficulty lifting, and extremity paresthesias) represented strongly clustered symptoms; whereas, syndromes 4 (\"phobia-apraxia\"), 5 (\"fever-adenopathy\"), and 6 (\"weakness-incontinence\") involved weaker clustering and mostly overlapped syndromes 2 and 3. " ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/15251045", "http://www.ncbi.nlm.nih.gov/pubmed/11600803", "http://www.ncbi.nlm.nih.gov/pubmed/14590665", "http://www.ncbi.nlm.nih.gov/pubmed/12446953", "http://www.ncbi.nlm.nih.gov/pubmed/9005271", "http://www.ncbi.nlm.nih.gov/pubmed/14515407", "http://www.ncbi.nlm.nih.gov/pubmed/9096828", "http://www.ncbi.nlm.nih.gov/pubmed/11478226", "http://www.ncbi.nlm.nih.gov/pubmed/21930452" ]

[]

[ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0007613", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D008569", "http://www.disease-ontology.org/api/metadata/DOID:4491", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D018923", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D008568" ]

[ "Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an inherited cerebral small vessel disease, clinically characterized by migraine, recurrent transient ischemic attacks or strokes, psychiatric disorders and cognitive decline. Strokes are typically ischemic, while hemorrhagic events have been only sporadically described. CADASIL is the most common form of hereditary cerebral angiopathy." ]

[ "yes" ]

[ " CADASIL is the most frequent hereditary small-vessel disease of the brain. The clinical impact of various MR imaging markers has been repeatedly studied in this disorder, but alterations of contrast between gray matter and normal-appearing white matter remain unknown. The aim of this study was to evaluate the contrast alterations between gray matter and normal-appearing white matter on T1-weighted images in patients with CADASIL compared with healthy subjects", " (CADASIL) is the most common form of hereditary cerebral angiopathy", "Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an inherited cerebral small vessel disease, clinically characterized by migraine, recurrent transient ischemic attacks or strokes, psychiatric disorders and cognitive decline. Strokes are typically ischemic, while hemorrhagic events have been only sporadically described", "Mutations in the TREX1 and NOTCH3 genes cause retinal vasculopathy with cerebral leukodystrophy (RVCL) and cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), respectively", "We used immunohistochemistry and immunogold electron microscopy (EM) to examine the distribution of GOM and NOTCH3 ectodomain (N3ECD) protein in microvasculature of brain gray matter and white matter in patients with CADASIL, non-CADASIL hereditary small-vessel disease and sporadic age-related degenerative disease, and comparable-age controls" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/23868154", "http://www.ncbi.nlm.nih.gov/pubmed/23355563", "http://www.ncbi.nlm.nih.gov/pubmed/23587639", "http://www.ncbi.nlm.nih.gov/pubmed/21772710", "http://www.ncbi.nlm.nih.gov/pubmed/23221354", "http://www.ncbi.nlm.nih.gov/pubmed/23832984", "http://www.ncbi.nlm.nih.gov/pubmed/23597439", "http://www.ncbi.nlm.nih.gov/pubmed/21197470", "http://www.ncbi.nlm.nih.gov/pubmed/24274803", "http://www.ncbi.nlm.nih.gov/pubmed/23465844", "http://www.ncbi.nlm.nih.gov/pubmed/23412372", "http://www.ncbi.nlm.nih.gov/pubmed/23602593", "http://www.ncbi.nlm.nih.gov/pubmed/23639391", "http://www.ncbi.nlm.nih.gov/pubmed/23799017", "http://www.ncbi.nlm.nih.gov/pubmed/23649698", "http://www.ncbi.nlm.nih.gov/pubmed/23799141", "http://www.ncbi.nlm.nih.gov/pubmed/23460375", "http://www.ncbi.nlm.nih.gov/pubmed/23705041", "http://www.ncbi.nlm.nih.gov/pubmed/23394849", "http://www.ncbi.nlm.nih.gov/pubmed/23584202", "http://www.ncbi.nlm.nih.gov/pubmed/23308019" ]

[ { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/diseaseontology/id/DOID:13945", "o": "UMLS_CUI:C0751587" }, { "p": "http://www.w3.org/2004/02/skos/core#prefLabel", "s": "http://linkedlifedata.com/resource/diseaseontology/id/DOID:13945", "o": "cadasil" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A8400718", "o": "C499374" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C1452875", "o": "http://linkedlifedata.com/resource/umls/label/A8407072" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A8400738", "o": "Notch homolog 3 (Drosophila) protein, human" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A8400718", "o": "NOTCH3 protein, human" }, { "p": "http://linkedlifedata.com/resource/umls/prefMetaMap", "s": "http://linkedlifedata.com/resource/umls/id/C1452875", "o": "http://linkedlifedata.com/resource/umls/label/A8400718" }, { "p": "http://linkedlifedata.com/resource/umls/altMetaMap", "s": "http://linkedlifedata.com/resource/umls/id/C1452875", "o": "http://linkedlifedata.com/resource/umls/label/A8407072" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C1452875", "o": "http://linkedlifedata.com/resource/umls/label/A8400738" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A8407072", "o": "CADASIL protein, human" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A8400738", "o": "C499374" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A8407072", "o": "C499374" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/diseaseontology/id/DOID:13945", "o": "MSH2010_2010_02_22:D046589" }, { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A8400718", "o": "MeSH" }, { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A8400738", "o": "MeSH" }, { "p": "http://www.w3.org/2004/02/skos/core#note", "s": "http://linkedlifedata.com/resource/umls/label/A8407072", "o": "MeSH" } ]

[ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D046589", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D020271", "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=D030342", "http://www.disease-ontology.org/api/metadata/DOID:4", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=diseases_category", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013577", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004194", "http://www.disease-ontology.org/api/metadata/DOID:13945" ]

[ "Neuroendocrine tumors are a heterogeneous group of benign and malignant neoplasias, detectable in the context of hereditary tumor syndromes in up to 30% of cases. Neuroendocrine tumors include medullary thyroid carcinoma, gastroenteropancreatic tumors, pheochromocytoma, and paraganglioma." ]

[ "medullary thyroid carcinoma", "gastroenteropancreatic tumors", "pheochromocytoma", "paraganglioma" ]

[ "Pheochromocytomas are neuroendocrine tumors of the adrenal medulla which can occur either sporadically or in the context of hereditary tumor syndromes", "Pheochromocytomas (PCCs) and paragangliomas (PGLs) are rare neuroendocrine tumors of the adrenal glands and the sympathetic and parasympathetic paraganglia. They can occur sporadically or as a part of different hereditary tumor syndromes", "Pancreatic neuroendocrine tumors (PNETs) are a characteristic feature of the tumor syndromes multiple endocrine neoplasia type 1 (MEN-1) and von Hippel-Lindau disease (VHL)", "This review focuses on hereditary syndromes with neuroendocrine tumors, including multiple endocrine neoplasia types 1 and 2, Von Hippel-Lindau disease, neurofibromatosis type 1, Carney complex, pheochromocytoma-paraganglioma syndrome, and familial nonmedullary thyroid carcinoma. In addition, several individual neuroendocrine tumors are described, such as medullary thyroid carcinoma, gastroenteropancreatic tumors, pheochromocytoma, and paraganglioma, emphasizing specific histopathologic characteristics", "Neuroendocrine tumors (NETs) are a heterogeneous group of benign and malignant neoplasias, detectable in the context of hereditary tumor syndromes in up to 30% of cases", "RET gene analysis can identify individuals with a very high risk to develop familial medullary cancer (MEN2)", "In addition, several individual neuroendocrine tumors are described, such as medullary thyroid carcinoma, gastroenteropancreatic tumors, pheochromocytoma, and paraganglioma, emphasizing specific histopathologic characteristics" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/23010473", "http://www.ncbi.nlm.nih.gov/pubmed/22041710", "http://www.ncbi.nlm.nih.gov/pubmed/21181474", "http://www.ncbi.nlm.nih.gov/pubmed/14685672", "http://www.ncbi.nlm.nih.gov/pubmed/19708762" ]

[]

[ "http://www.disease-ontology.org/api/metadata/DOID:169" ]

[ "Investigators proposed that there have been three extended periods in the evolution of gene regulatory elements. Early vertebrate evolution was characterized by regulatory gains near transcription factors and developmental genes, but this trend was replaced by innovations near extracellular signaling genes, and then innovations near posttranslational protein modifiers." ]

[ "Three" ]

[ "Three periods of regulatory innovation during vertebrate evolution.", "To investigate the gain of regulatory elements throughout vertebrate evolution, we identified genome-wide sets of putative regulatory regions for five vertebrates, including humans. These putative regulatory regions are conserved nonexonic elements (CNEEs), which are evolutionarily conserved yet do not overlap any coding or noncoding mature transcript. We then inferred the branch on which each CNEE came under selective constraint. Our analysis identified three extended periods in the evolution of gene regulatory elements. Early vertebrate evolution was characterized by regulatory gains near transcription factors and developmental genes, but this trend was replaced by innovations near extracellular signaling genes, and then innovations near posttranslational protein modifiers.", "Early vertebrate evolution was characterized by regulatory gains near transcription factors and developmental genes, but this trend was replaced by innovations near extracellular signaling genes, and then innovations near posttranslational protein modifiers.", "Our analysis identified three extended periods in the evolution of gene regulatory elements. ", "Our analysis identified three extended periods in the evolution of gene regulatory elements. Early vertebrate evolution was characterized by regulatory gains near transcription factors and developmental genes, but this trend was replaced by innovations near extracellular signaling genes, and then innovations near posttranslational protein modifiers.", "Our analysis identified three extended periods in the evolution of gene regulatory elements. Early vertebrate evolution was characterized by regulatory gains near transcription factors and developmental genes, but this trend was replaced by innovations near extracellular signaling genes, and then innovations near posttranslational protein modifiers.", "We then inferred the branch on which each CNEE came under selective constraint. Our analysis identified three extended periods in the evolution of gene regulatory elements.", "Our analysis identified three extended periods in the evolution of gene regulatory elements.", "Early vertebrate evolution was characterized by regulatory gains near transcription factors and developmental genes, but this trend was replaced by innovations near extracellular signaling genes, and then innovations near posttranslational protein modifiers." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/21852499" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D014714", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005075" ]

[ "Yes, nintedanib is approved for Idiopathic Pulmonary Fibrosis treatment. Nintedanib was shown to slow the decline in lung function, decrease acute exacerbations, decrease the annual rate of decline in forced vital capacity and increase time to acute exacerbation." ]

[ "yes" ]

[ "In this review, we present the positive results of recently published clinical trials regarding therapy for IPF, with emphasis on pirfenidone and nintedanib.", "Nintedanib: evidence for its therapeutic potential in idiopathic pulmonary fibrosis", " In the Phase II TOMORROW trial, treatment with 150 mg of nintedanib twice daily showed a trend to slow the decline in lung function and significantly decrease acute exacerbations in patients with IPF, while showing an acceptable safety profile. The Phase III INPULSIS trials demonstrated a significant decrease in the annual rate of decline in forced vital capacity in IPF patients treated with 150 mg nintedanib twice daily. In the INPULSIS-2 trial, the time to the first acute exacerbation significantly increased in IPF patients who were treated with 150 mg of nintedanib twice daily.", " Effects on collagen secretion were compared with those of the drugs nintedanib and pirfenidone, recently approved for IPF.", "Nintedanib, an orally available, small-molecule tyrosine kinase inhibitor with selectivity for vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF) and fibroblast growth factor (FGF) receptors has recently been shown, in two pivotal phase III studies, to effectively slow IPF disease progression. Consequently, nintedanib was given accelerated approval by the FDA in October 2014 for the treatment of IPF. ", "Most recently, pirfenidone and nintedanib, two compounds with pleiotropic anti-fibrotic properties, have been proven effective in reducing functional decline and disease progression in IPF. ", "Meningococcal group B vaccine (Trumenba) to prevent more types of invasive meningococcal disease; antihemophilic factor (recombinant), porcine sequence (Obizur) to treat bleeding from acquired hemophilia A; and pirfenidone (Esbriet) and nintedanib (Ofev) for idiopathic pulmonary fibrosis.", " More importantly, the period ends with the publication of two groundbreaking studies that confirmed that two drugs, pirfenidone and nintedanib, slowed disease progression, leading to a historic approval by the FDA. ", "Nintedanib (Ofev(®)) is an orally available, small, multiple receptor tyrosine kinase inhibitor developed by Boehringer Ingelheim for the treatment of idiopathic pulmonary fibrosis (IPF) and cancer. Nintedanib received its first global approval in the US in October 2014 for the treatment of IPF. Nintedanib has received a positive opinion from the European Medicines Agency's Committee for Medicinal Products for Human Use for the treatment of IPF, and for the second-line treatment in combination with docetaxel of locally advanced, metastatic or locally recurrent non-small cell lung cancer of adenocarcinoma tumour histology. ", "This article summarizes the milestones in the development of nintedanib leading to this first approval for IPF.", "Efficacy and safety of nintedanib in idiopathic pulmonary fibrosis.", "Nintedanib: a novel therapeutic approach for idiopathic pulmonary fibrosis.", "Nintedanib is in clinical development as a treatment for idiopathic pulmonary fibrosis (IPF).", "Reducing lung function decline in patients with idiopathic pulmonary fibrosis: potential of nintedanib.", "These results suggest that nintedanib may impact the progressive course of fibrotic lung diseases such as idiopathic pulmonary fibrosis.", "Findings from recently published placebo-controlled trials in idiopathic pulmonary fibrosis have established that pirfenidone and nintedanib prevent about 50% of the decline in forced vital capacity typically seen in this disease; future trials are therefore unlikely to use placebo as a control group for ethical reasons.", "The tyrosine kinase inhibitor nintedanib (BIBF 1120) is in clinical development for the treatment of idiopathic pulmonary fibrosis.", "A phase 2 trial suggested that treatment with 150 mg of nintedanib twice daily reduced lung-function decline and acute exacerbations in patients with idiopathic pulmonary fibrosis.", "A phase 2 trial suggested that treatment with 150 mg of nintedanib twice daily reduced lung-function decline and acute exacerbations in patients with idiopathic pulmonary fibrosis. ", "Data from the Phase II TOMORROW study suggested that nintedanib 150�mg twice daily had clinical benefits with an acceptable safety profile.METHODS: The INPULSIS� trials are replicate Phase III, randomized, double-blind, studies comparing the efficacy and safety of nintedanib 150�mg twice daily with placebo in patients with IPF. ", "Nintedanib received its first global approval in the US in October 2014 for the treatment of IPF. ", "The most frequent adverse event in the nintedanib groups was diarrhea, with rates of 61.5% and 18.6% in the nintedanib and placebo groups, respectively, in INPULSIS-1 and 63.2% and 18.3% in the two groups, respectively, in INPULSIS-2. CONCLUSIONS: In patients with idiopathic pulmonary fibrosis, nintedanib reduced the decline in FVC, which is consistent with a slowing of disease progression; nintedanib was frequently associated with diarrhea, which led to discontinuation of the study medication in less than 5% of patients. ", "A phase 2 trial suggested that treatment with 150 mg of nintedanib twice daily reduced lung-function decline and acute exacerbations in patients with idiopathic pulmonary fibrosis. METHODS: We conducted two replicate 52-week, randomized, double-blind, phase 3 trials (INPULSIS-1 and INPULSIS-2) to evaluate the efficacy and safety of 150 mg of nintedanib twice daily as compared with placebo in patients with idiopathic pulmonary fibrosis. ", "Nintedanib (Ofev(�)) is an orally available, small, multiple receptor tyrosine kinase inhibitor developed by Boehringer Ingelheim for the treatment of idiopathic pulmonary fibrosis (IPF) and cancer. Nintedanib received its first global approval in the US in October 2014 for the treatment of IPF. ", "Nintedanib: evidence for its therapeutic potential in idiopathic pulmonary fibrosis.", "A phase 2 trial suggested that treatment with 150 mg of nintedanib twice daily reduced lung-function decline and acute exacerbations in patients with idiopathic pulmonary fibrosis. We conducted two replicate 52-week, randomized, double-blind, phase 3 trials (INPULSIS-1 and INPULSIS-2) to evaluate the efficacy and safety of 150 mg of nintedanib twice daily as compared with placebo in patients with idiopathic pulmonary fibrosis." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/25628503", "http://www.ncbi.nlm.nih.gov/pubmed/26261848", "http://www.ncbi.nlm.nih.gov/pubmed/24834811", "http://www.ncbi.nlm.nih.gov/pubmed/26039104", "http://www.ncbi.nlm.nih.gov/pubmed/25430078", "http://www.ncbi.nlm.nih.gov/pubmed/24782550", "http://www.ncbi.nlm.nih.gov/pubmed/26380465", "http://www.ncbi.nlm.nih.gov/pubmed/24556663", "http://www.ncbi.nlm.nih.gov/pubmed/23818761", "http://www.ncbi.nlm.nih.gov/pubmed/24836310", "http://www.ncbi.nlm.nih.gov/pubmed/25767391", "http://www.ncbi.nlm.nih.gov/pubmed/25439569", "http://www.ncbi.nlm.nih.gov/pubmed/26346347", "http://www.ncbi.nlm.nih.gov/pubmed/25635490" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D054990", "http://www.disease-ontology.org/api/metadata/DOID:0050156" ]

[ "Diabetic cardiomyopathy is accompanied by reduced SERCA levels and activity in later stages. The up-regulation of SERCA2a in the early phase of type 2 diabetes is an important physiological adaptation of the heart." ]

[]

[ "Compared with control group, [Ca(2+)](i) and the expression of CaSR, RyR and SERCA/PLN were decreased, while PKC-α and PLN were significantly increased in a time-dependent manner in diabetic group", "Diabetic rats showed impaired cardiac structure and function compared with control rats. The expression of PKC, PLB increased significantly, while the PPI-1, SERCA-2 and RyR expression decreased. Treatment with breviscapine could reverse the cardiac dysfunction and structure changes in diabetic cardiomyopathy rats, and decrease the expression of PKC and PLB, as well as increase the expression of PPI-1, SERCA-2 and RyR.", "Diabetic Ren-2 rats developed impairment of both active and passive phases of diastole, accompanied by reductions in SERCA-2a ATPase and phospholamban along with activation of the fetal gene program.", "The levels of SERCA and GLUT4, but not PLB, were significantly reduced in diabetic hearts compared with controls.", "CONCLUSIONS: CASQ2, FKBP12.6 and SERCA2a were down-regulated in diabetic cardiomyopathy.", "Reduced sarcoplasmic calcium ATPase (SERCA2a) expression has been shown to play a significant role in the cardiac dysfunction in diabetic cardiomyopathy.", "Depressed sarcoplasmic reticulum (SR) Ca(2+)-ATPase (SERCA2a) and Ca(2+)-release channels (ryanodine receptor RyR2) are involved in diabetic cardiomyopathy, however, the implication of intracellular calcium handling proteins in SR is undefined.", "The depressed sarcoplasmic reticulum (SR) Ca2+-ATPase (SERCA2a) and Ca2+-release channels (ryanodine receptor RyR2) are involved in the diabetic cardiomyopathy.", "Slowed relaxation in diabetic cardiomyopathy (CM) is partially related to diminished expression of the sarcoplasmic reticulum (SR) Ca2+-ATPase SERCA2a." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/18570267", "http://www.ncbi.nlm.nih.gov/pubmed/16810072", "http://www.ncbi.nlm.nih.gov/pubmed/22137362", "http://www.ncbi.nlm.nih.gov/pubmed/20008278", "http://www.ncbi.nlm.nih.gov/pubmed/22621761", "http://www.ncbi.nlm.nih.gov/pubmed/12217882", "http://www.ncbi.nlm.nih.gov/pubmed/19882101", "http://www.ncbi.nlm.nih.gov/pubmed/12206992", "http://www.ncbi.nlm.nih.gov/pubmed/21441944", "http://www.ncbi.nlm.nih.gov/pubmed/17716638", "http://www.ncbi.nlm.nih.gov/pubmed/18492789", "http://www.ncbi.nlm.nih.gov/pubmed/22590623" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D003920", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D058065", "http://www.uniprot.org/uniprot/AT2A_CHIOP", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D003924", "http://www.disease-ontology.org/api/metadata/DOID:9351" ]

[ "Yes, it is associated with peripheral neuropathy.", "Yes, pesticide exposure is associated with delayed polyneuropathy. Electrophysiological studies have revealed three characteristic phenomena: (i) repetitive firing following a single stimulus; (ii) gradual reduction in twitch height or compound muscle action potential followed by an increase with repetitive stimulation (the 'decrement-increment response'); and (iii) continued reduction in twitch height or compound muscle action potential with repetitive simulation ('decrementing response'). Pesticide exposure was also implicated in Alzheimer's disease, suicide attempts and affective disorders." ]

[ "yes" ]

[ "As the syndrome occurred after the acute cholinergic syndrome but before organophosphate-induced delayed polyneuropathy, the syndrome was called 'intermediate syndrome'.", "The characteristic features of the IMS are weakness of the muscles of respiration (diaphragm, intercostal muscles and accessory muscles including neck muscles) and of proximal limb muscles. Accompanying features often include weakness of muscles innervated by some cranial nerves. It is now emerging that the degree and extent of muscle weakness may vary following the onset of the IMS. ", "Electrophysiological studies following OP poisoning have revealed three characteristic phenomena: (i) repetitive firing following a single stimulus; (ii) gradual reduction in twitch height or compound muscle action potential followed by an increase with repetitive stimulation (the 'decrement-increment response'); and (iii) continued reduction in twitch height or compound muscle action potential with repetitive simulation ('decrementing response'). ", "Organophosphate-induced delayed polyneuropathy is a sensory-motor distal axonopathy which usually occurs after exposure of certain OP insecticides. Neuropathies due to ingestion of OPs have rarely been reported in the literature.", "We report a patient with serious organophosphorus-induced delayed neuropathy due to malathion injection. The patient was a 32-year-old female who self-injected undetermined amounts of malathion over the median nerve trace on the forearm crease in a suicide attempt which resulted in peripheral neuropathy.", " Acutely, these patients present with cholinergic crisis; intermediate syndrome and delayed polyneuropathy are other sequel of this form of poisoning.", "There was no strong evidence of irreversible peripheral nerve damage following acute OP poisoning, however further studies are required.", "Particular interactions are also addressed, such as those of pesticides acting as endocrine disruptors, the cumulative toxicity of organophosphates and organochlorines resulting in estrogenic effects and the promotion of organophosphate-induced delayed polyneuropathy.", "The multivariate analyses showed that the population living in areas with high pesticide use had an increased risk for Alzheimer's disease and suicide attempts and that males living in these areas had increased risks for polyneuropathies, affective disorders and suicide attempts. ", "These compounds cause four important neurotoxic effects in humans: the cholinergic syndrome, the intermediate syndrome, organophosphate-induced delayed polyneuropathy (OPIDP) and chronic organophosphate-induced neuropsychiatric disorder (COPIND). ", "An 18-year-old woman and a 22-year-old man were admitted to the hospital with weakness, paresthesia, and gait disturbances at 35 and 22 days, respectively, after ingesting dimethyl-2,2-dichloro vinyl phosphate (DDVP). Neurological examination revealed weakness, vibration sense loss, bilateral dropped foot, brisk deep tendon reflexes, and bilaterally positive Babinski sign. Electroneurography demonstrated distal motor polyneuropathy with segmental demyelination associated with axonal degeneration prominent in the distal parts of both lower extremities.", "Sensory complaints and electrodiagnostic findings consistent with polyneuropathy were found in a minority (3/7) of subjects 28 years after an acute toxic arsenic exposure.", "Organophosphate-induced delayed polyneuropathy (OPIDP) is a rare toxicity resulting from exposure to certain organophosphorus (OP) esters. ", "Therefore, OPIDP may develop only after very large exposures to insecticides, causing severe cholinergic toxicity.", "Several studies have reported the occurrence of sensory neuropathy with exposure to chlorpyrifos and other organophosphorus insecticides, at levels not associated with overt toxicity. ", "We found no evidence of sensory neuropathy or isolated peripheral abnormalities among subjects with long-term chlorpyrifos exposure at levels known to be associated with the manufacturing process.", "Persistent, mainly motor, impairment of the peripheral nervous system was found in men two years after OP poisoning, in particular in severe occupational and intentional poisonings with neuropathic OPs. This finding is possibly due to remaining organophosphate induced delayed polyneuropathy.", "Besides the well known acute cholinergic toxicity, these compounds may cause late-onset distal polyneuropathy occurring two to three weeks after the acute exposure. ", "Electromyography demonstrated motor weighed sensory-motor polyneuropathy with axonal degeneration significant in the distal parts of bilateral lower extremities. ", "The two cases are presented here since organophosphate poisonings are common in our country, and since late-onset polyneuropathy is not a well known clinical presentation as acute toxicity.", "The course of organophosphate-induced delayed polyneuropathy (OPIDP) in humans has not been quantitatively measured in epidemiologic studies.", "The persistence of deficits in motor strength in all severely poisoned patients regardless of pesticide type was unexpected, and may reflect persistent cholinergic blockade or intermediate syndrome, neuropathy, or a combination of these.", "The findings showed a strong association between exposure to OP concentrate and neurological symptoms, but a less consistent association with sensory thresholds. ", "Following accidental or suicidal exposure, these anticholinesterases lead to three well defined neurological syndromes i.e. initial life threatening acute cholinergic crisis which often requires management in intensive care unit, intermediate syndrome in which cranial nerve palsies, proximal muscle weakness and respiratory muscle weakness are common and patients often require respiratory support and delayed organophosphate induced polyneuropathy.", "[Late onset polyneuropathy due to exposure to organophosphates].", " Less often a polyneuropathic syndrome of late onset may occur.", "On electromyography there was sensomotor peripheral polyneuropathy, which was primarily axonal and predominantly motor and distal. Peripheral nerve biopsy confirmed the presence of 'dying back' type axonopathy. ", "Agricultural workers chronically exposed to organophosphate insecticides, without adequate protection, have an increased risk of developing late onset neuropathy due to organophosphates. ", "Epidemiologic studies on pesticides have found associations with long-term effects on health mainly in three fields: cancer (especially hematological cancer), neurotoxic effects (polyneuropathy, neuro-behavioral hazards, Parkinson's disease), and reproductive disorders (infertility, birth defects, adverse pregnancy outcomes, perinatal mortality). ", "EMG studies showed evidence of partial denervation of the anterior tibial group of muscles and flexor digiti minimi in 2 of the 30 workers (6.7%) who underwent EMG examination.", "Neurological symptoms consist in cerebro-organic disfunctions, locomotory disorders reminiscent of multiple sclerosis or M. Parkinson, and sensory, motoric and vegetative polyneuropathy, leading, for instance, to cardiovascular regulatory disorder like sympathicotonia or, orthostatic hypotonia. ", "Thirty percent of patients had definite or possible exposure to organophosphate pesticides, and the peak use coincides with the peak incidence of Guillain-Barré syndrome.", "These results suggest that previously reported cases of organophosphate-induced delayed polyneuropathy may represent only the worst disease in a spectrum of impairment, a sequela of exposure that may be much more common than previously thought.", "It is suggested that the main cause of nervous lesions in these cases was the complex effect of pesticides.", "Delayed polyneuropathy develops within 1 to 3 weeks and abates after 6 to 12 months. ", "Isolated case reports have circumstantially linked the use of the herbicide 2,4-dichlorophenoxyacetic acid (2,4-D) to polyneuropathy.", "Thus, the weight of evidence indicates that 2,4-D is an unlikely cause of polyneuropathy.", "A patient is reported presenting a cerebellar disorder developing about 5 weeks after acute exposure to an organophosphate insecticide. ", "Less well known, but more complex and idiosyncratic, is the potential for some agents to produce a delayed and progressive polyneuropathy--Organophosphorus Induced Delayed Neurotox-icity (OPIDN).", " It is also quite probable that human neurotoxicity may be a potential hazard from exposure to more than the handful of organophosphorus pesticides that have been described in the literature.", "In the present study the electroencephalograms of 3 of a group 10 workmen, who had been continually exposed to hexachlorcyclohexane, show pathological findings. The electromyograms of 8 of these 10 workman demonstrate a disturbance of the peripherical motoneuron. All probands, who exhibit o pathological EEG, also show a polyneuropathy.", "Many organophosphorus compounds, including the organophosphate insecticides, may cause polyneuropathy of delayed onset.", "Nevertheless, we describe a patient with delayed polyneuropathy after suicidal ingestion of parathion.", "Following acute organophosphorus (OP) poisoning patients complain of numbness without objective sensory abnormalities or other features of OP induced delayed polyneuropathy. " ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/2158793", "http://www.ncbi.nlm.nih.gov/pubmed/23251840", "http://www.ncbi.nlm.nih.gov/pubmed/23251841", "http://www.ncbi.nlm.nih.gov/pubmed/16140621", "http://www.ncbi.nlm.nih.gov/pubmed/21432383", "http://www.ncbi.nlm.nih.gov/pubmed/19079407", "http://www.ncbi.nlm.nih.gov/pubmed/22728724", "http://www.ncbi.nlm.nih.gov/pubmed/23185328", "http://www.ncbi.nlm.nih.gov/pubmed/21787602", "http://www.ncbi.nlm.nih.gov/pubmed/12718377", "http://www.ncbi.nlm.nih.gov/pubmed/7998771", "http://www.ncbi.nlm.nih.gov/pubmed/15116371", "http://www.ncbi.nlm.nih.gov/pubmed/17107865", "http://www.ncbi.nlm.nih.gov/pubmed/14691285", "http://www.ncbi.nlm.nih.gov/pubmed/7194975", "http://www.ncbi.nlm.nih.gov/pubmed/10528323", "http://www.ncbi.nlm.nih.gov/pubmed/21258583", "http://www.ncbi.nlm.nih.gov/pubmed/9311548", "http://www.ncbi.nlm.nih.gov/pubmed/11600725", "http://www.ncbi.nlm.nih.gov/pubmed/16856766", "http://www.ncbi.nlm.nih.gov/pubmed/16042503", "http://www.ncbi.nlm.nih.gov/pubmed/16702122", "http://www.ncbi.nlm.nih.gov/pubmed/19922373", "http://www.ncbi.nlm.nih.gov/pubmed/7787373", "http://www.ncbi.nlm.nih.gov/pubmed/11146591", "http://www.ncbi.nlm.nih.gov/pubmed/21601587", "http://www.ncbi.nlm.nih.gov/pubmed/22399093", "http://www.ncbi.nlm.nih.gov/pubmed/23703814", "http://www.ncbi.nlm.nih.gov/pubmed/22262687", "http://www.ncbi.nlm.nih.gov/pubmed/1481520", "http://www.ncbi.nlm.nih.gov/pubmed/8160653", "http://www.ncbi.nlm.nih.gov/pubmed/11843436", "http://www.ncbi.nlm.nih.gov/pubmed/6179111", "http://www.ncbi.nlm.nih.gov/pubmed/9592856", "http://www.ncbi.nlm.nih.gov/pubmed/11045057", "http://www.ncbi.nlm.nih.gov/pubmed/22655091", "http://www.ncbi.nlm.nih.gov/pubmed/2707289", "http://www.ncbi.nlm.nih.gov/pubmed/2462700", "http://www.ncbi.nlm.nih.gov/pubmed/18780003", "http://www.ncbi.nlm.nih.gov/pubmed/21120082", "http://www.ncbi.nlm.nih.gov/pubmed/1665780" ]

[]

[ "http://www.disease-ontology.org/api/metadata/DOID:1389", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011115", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004781", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016273", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D010575" ]

[ "Chromatin interaction analysis with paired-end tag sequencing (ChIA-PET) is a new technology to study genome-wide long-range chromatin interactions bound by protein factors. To minimize non-specific noise and reduce complexity, as well as to increase the specificity of the chromatin interaction analysis, chromatin immunoprecipitation (ChIP) is used against specific protein factors to enrich chromatin fragments of interest before proximity ligation. Combining Chromatin Immunoprecipitation (ChIP), proximity ligation and high-throughput sequencing, ChIA-PET provides a global and unbiased interrogation of higher-order chromatin structures associated with specific protein factors. Here, we propose a statistical model taking into account the genomic distance relationship, as well as the general propensity of anchors to be involved in contacts overall.", "Chromatin interaction analysis with paired-end tag sequencing (ChIA-PET) is a new technology to study genome-wide long-range chromatin interactions bound by protein factors. It converts functional chromatin structure into millions of short tag sequences. By combining Chromatin Immunoprecipitation (ChIP), proximity ligation and high-throughput sequencing, ChIA-PET provides a global and unbiased interrogation of higher-order chromatin structures associated with specific protein factors." ]

[]

[ "Overall we show that ChIA-PET is the cornerstone to explore the three-dimensional (3D) chromatin structure, and certainly will lead the forthcoming wave of 3D genomics studies.", "Chromatin interaction analysis with paired-end tag sequencing (ChIA-PET) is a new technology to study genome-wide long-range chromatin interactions bound by protein factors. ", "Chromatin Interaction Analysis using Paired-End Tag sequencing (ChIA-PET) is a method which converts functional chromatin structure into millions of short tag sequences. Combining Chromatin Immunoprecipitation (ChIP), proximity ligation and high-throughput sequencing, ChIA-PET provides a global and unbiased interrogation of higher-order chromatin structures associated with specific protein factors.", "Chromatin Interaction Analysis by Paired-End Tag Sequencing (ChIA-PET) was developed to identify these higher-order chromatin structures", " ChIA-PET is a novel method to identify such interactions, where physical contacts between regions bound by a specific protein are quantified using next-generation sequencing. ", "Proximity ligation assays commonly known as chromosome conformation capture (3C) and 3C based methodologies (e.g., GCC, HiC and ChIA-Pet) are increasingly being incorporated into empirical studies to investigate the role that three-dimensional genome structure plays in the regulation of phenotype." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/20181287", "http://www.ncbi.nlm.nih.gov/pubmed/25563301", "http://www.ncbi.nlm.nih.gov/pubmed/22564980", "http://www.ncbi.nlm.nih.gov/pubmed/22926262", "http://www.ncbi.nlm.nih.gov/pubmed/24051548", "http://www.ncbi.nlm.nih.gov/pubmed/25114054" ]

[]

[]

[ "There is no data to suggest an association between borna virus and brain tumor. Borna disease virus establishes a persistent infection in the central nervous system of vertebrate animal species as well as in tissue cultures causing cellular damage. Infected neural cells, include astrocytes, neurons, oligodendroglioma cell line. Borna disease virus replicates and can cause damage of brain cells." ]

[ "no" ]

[ "Borna disease virus (BDV), a nonsegmented, negative-strand RNA virus, infects a wide variety of mammalian species and readily establishes a long-lasting, persistent infection in brain cells. ", "To investigate the biological characteristics of field isolates of Borna disease virus (BDV), as well as to understand BDV infections outside endemic countries, we isolated the virus from brain samples of a heifer with Borna disease in Japan.", "Neonatal Borna disease virus (BDV) infection of the rat brain is associated with microglial activation and damage to the certain neuronal populations.", "In addition, compared to uninfected mixed cultures, activation of microglia in BDV-infected mixed cultures was associated with a significantly greater lipopolysaccharide-induced release of tumor necrosis factor alpha, interleukin 1beta, and interleukin 10. Taken together, the present data are the first in vitro evidence that persistent BDV infection of neurons and astrocytes rather than direct exposure to the virus or dying neurons is critical for activating microglia.", "Usually, Borna disease virus is not cleared from the brain but rather persists in neural cells.", "Varied persistent life cycles of Borna disease virus in a human oligodendroglioma cell line.", "Borna disease virus (BDV) establishes a persistent infection in the central nervous system of vertebrate animal species as well as in tissue cultures. ", "Thus, our findings show that BDV may have established a persistent infection at low levels of viral expression in OL cells with the possibility of a latent infection.", "These results suggested that BDV infection may cause direct damage in the developing brain by inhibiting the function of amphoterin due to binding by the p24 phosphoprotein.", "We describe a model for investigating disorders of central nervous system development based on neonatal rat infection with Borna disease virus, a neurotropic noncytolytic RNA virus. ", "Borna disease virus (BDV) replicates in brain cells. The neonatally infected rat with BDV exhibits developmental-neuromorphological abnormalities, neuronal cytolysis, and multiple behavioral and physiological alterations. ", "Borna disease virus (BDV) causes central nervous system (CNS) disease in several vertebrate species, which is frequently accompanied by behavioral abnormalities.", "Intrinsic responses to Borna disease virus infection of the central nervous system.", "Immune cells invading the central nervous system (CNS) in response to Borna disease virus (BDV) antigens are central to the pathogenesis of Borna disease (BD). ", "We report here the partial purification and characterization of cell-free BDV from the tissue culture supernatant of infected human neuroblastoma SKNSH cells.", "We have used the reverse transcriptase-polymerase chain reaction technique to gain insight into the pathogenesis of encephalitis caused by Borna disease virus (BDV). ", "In contrast, in the BDV-infected primary mixed cultures, we observed proliferation of microglia cells that acquired the round morphology and expressed major histocompatibility complex molecules of classes I and II." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/10483922", "http://www.ncbi.nlm.nih.gov/pubmed/10227422", "http://www.ncbi.nlm.nih.gov/pubmed/1731117", "http://www.ncbi.nlm.nih.gov/pubmed/17020949", "http://www.ncbi.nlm.nih.gov/pubmed/11507219", "http://www.ncbi.nlm.nih.gov/pubmed/11070091", "http://www.ncbi.nlm.nih.gov/pubmed/21937656", "http://www.ncbi.nlm.nih.gov/pubmed/8917593", "http://www.ncbi.nlm.nih.gov/pubmed/15596826", "http://www.ncbi.nlm.nih.gov/pubmed/8184547", "http://www.ncbi.nlm.nih.gov/pubmed/10518583", "http://www.ncbi.nlm.nih.gov/pubmed/11907227", "http://www.ncbi.nlm.nih.gov/pubmed/22848506" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001890", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001891", "http://www.disease-ontology.org/api/metadata/DOID:1319", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001932", "http://www.disease-ontology.org/api/metadata/DOID:5154" ]

[ "Deoxycoformycin and pentostatin are purine analogs that interfere with purine metabolism and are used for treatment of T-cell prolymphocytic leukemia patients." ]

[ "deoxycoformycin", "pentostatin", "nelarabine" ]

[ "Treatment with purine analogues and alemtuzumab has resulted in significantly higher response rates and improved survival. ", " Treatment with purine analogs and the monoclonal antibody alemtuzumab has resulted in significantly higher response rates and increased survival.", "Nelarabine is an effective regimen against indolent leukemias, and combining it with fludarabine was most promising. Determination of tumor cell ara-GTP levels may provide a predictive test for response to nelarabine.", "T-cell prolymphocytic leukemia has an aggressive course with short median survival and poor response to chemotherapy. With the use of the purine analogue pentostatin more than half of patients will have a major response and a minority will have a complete remission, usually lasting months.", " T-cell prolymphocytic leukaemia (T-PLL) is a rare post-thymic T-cell malignancy with an aggressive clinical course. It has generally been resistant to alkylating chemotherapy, but some effect has been observed with the purine analog 2-deoxycoformicin with documented partial or complete response rates in up to 45% of patients.", "Fifteen patients with T-PLL, most of whom had received the purine analog deoxycoformycin (DCF), were treated with CAMPATH-1H.", "Pentostatin (2'-deoxycoformycin; DCF) is a purine analogue that has shown activity in treatment of chronic lymphoid malignancies.", "Trials using DCF or other purine analogues alone or in combination with standard chemotherapeutic agents in front-line or salvage therapy are warranted to improve the prognosis of patients with prolymphocytic leukemia." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/18039954", "http://www.ncbi.nlm.nih.gov/pubmed/22538464", "http://www.ncbi.nlm.nih.gov/pubmed/23512246", "http://www.ncbi.nlm.nih.gov/pubmed/19915381", "http://www.ncbi.nlm.nih.gov/pubmed/18309944", "http://www.ncbi.nlm.nih.gov/pubmed/19778847", "http://www.ncbi.nlm.nih.gov/pubmed/19275513", "http://www.ncbi.nlm.nih.gov/pubmed/12447847", "http://www.ncbi.nlm.nih.gov/pubmed/8468724", "http://www.ncbi.nlm.nih.gov/pubmed/15869731", "http://www.ncbi.nlm.nih.gov/pubmed/22483155", "http://www.ncbi.nlm.nih.gov/pubmed/9215839", "http://www.ncbi.nlm.nih.gov/pubmed/15039804" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D008660", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013812", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0006144", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0042278", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0006163", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011684", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D015461", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011687" ]

[ "Recent data demonstrate that developmental transcription factors like the macrophage fate-determining Pu.1 set the stage for the activity of ubiquitous transcription factors activated by inflammatory stimuli, like NF-kB, AP-1, and interferon regulatory factors (IRFs). Within 1217 bp of upstream sequence, 3 sites for NF-kB, 10 sites for NF-IL6, 15 sites for AP1, 6 sites for AP4, 2 sites for CHOP/CEBP alpha and 1 site for SP1 and PU.1 were identified.", "Recent data demonstrate that developmental transcription factors like the macrophage fate-determining Pu.1 set the stage for the activity of ubiquitous transcription factors activated by inflammatory stimuli, like NF-kB, AP-1, and interferon regulatory factors (IRFs)." ]

[ "yes" ]

[ "Recent data demonstrate that developmental transcription factors like the macrophage fate-determining Pu.1 set the stage for the activity of ubiquitous transcription factors activated by inflammatory stimuli, like NF-kB, AP-1, and interferon regulatory factors (IRFs).", "Within 1217 bp of upstream sequence, 3 sites for NF-kB, 10 sites for NF-IL6, 15 sites for AP1, 6 sites for AP4, 2 sites for CHOP/CEBP alpha and 1 site for SP1 and PU.1 were identified.", "As little as 82 bp of upstream sequence gave relatively strong luciferase activity, a region containing both a PU.1 and NF-kB site.", "Potential transcription regulatory elements, AP1, AP2, AP3, NF-kB and GATA recognition sequences, are located within 523 bp upstream of the p35 gene; however, no TATA box was identified. The p40 subunit gene consists of eight exons. A TATA box is located 30 bp upstream from the transcription start site, and AP1, AP3, GATA, and Pu.1 recognition sequences are located within 690 bp upstream of the p40 gene.", "Several putative binding sequences for ubiquitous (Sp1, AP-1, AP-2, and NF-kB) and leukocyte-specific (PU.1) transcription factors have been identified in the proximal region of the CD11c promoter which may participate in the regulation of the expression of p150,95.", "PU.1 is regulated by NF-kappaB through a novel binding site in a 17 kb upstream enhancer element." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/19966852", "http://www.ncbi.nlm.nih.gov/pubmed/12020825", "http://www.ncbi.nlm.nih.gov/pubmed/7678251", "http://www.ncbi.nlm.nih.gov/pubmed/21245163", "http://www.ncbi.nlm.nih.gov/pubmed/8647196", "http://www.ncbi.nlm.nih.gov/pubmed/10023076" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016328" ]

[ "A large number of mitochondrial genomes significantly deviate from the 2nd parity rule, in contrast to the eubacterial ones. This behaviour of the large majority of the mitochondrial genomes may be attributed to their distinct mode of replication, which is fundamentally different from the one of the eubacteria." ]

[ "no" ]

[ "a large number of mitochondrial genomes significantly deviate from the 2nd parity rule in contrast to the eubacterial ones", "mitochondria may be divided into three distinct sub-groups according to their overall deviation from the aforementioned parity rule.", "The behaviour of the large majority of the mitochondrial genomes may be attributed to their distinct mode of replication, which is fundamentally different from the one of the eubacteria.", "We tested all available organellar genomes and found that a large number of mitochondrial genomes significantly deviate from the 2nd parity rule in contrast to the eubacterial ones, although mitochondria are believed to have evolved from proteobacteria.", "The behaviour of the large majority of the mitochondrial genomes may be attributed to their distinct mode of replication, which is fundamentally different from the one of the eubacteria.", "We tested all available organellar genomes and found that a large number of mitochondrial genomes significantly deviate from the 2nd parity rule in contrast to the eubacterial ones, although mitochondria are believed to have evolved from proteobacteria.", "The behaviour of the large majority of the mitochondrial genomes may be attributed to their distinct mode of replication, which is fundamentally different from the one of the eubacteria", "We tested all available organellar genomes and found that a large number of mitochondrial genomes significantly deviate from the 2nd parity rule in contrast to the eubacterial ones, although mitochondria are believed to have evolved from proteobacteria" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/16893615", "http://www.ncbi.nlm.nih.gov/pubmed/17562011", "http://www.ncbi.nlm.nih.gov/pubmed/11675596" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D054629", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0000262" ]

[ "Greater h-index is associated with greater academic rank in academic neurosurgery. The h indices increased significantly with increasing academic rank, with the median for instructors, assistant professors, associate professors, and professors was shown to be 2, 5, 10, and 19, respectively. In addition, h-index was shown to be predictive of NIH funding, fellowship training, academic productivity and salary." ]

[]

[ " The contemporary h-index was found to be significantly predictive of NIH funding (p<0.001). ", "Bibliometric indices are higher for those with NIH funding compared to those without, but only the contemporary h-index was shown to be predictive of NIH funding. ", "However, when stratified by academic rank, a trend was observed showing greater mean h-index scores for those who completed fellowships. ", "Overall, being a senior faculty member corresponds with a greater h-index score, regardless of whether a fellowship was completed.", "There was a positive association between the h-index, academic rank, and years posttraining.", "Application of the h-index as a bibliometric in neurosurgery can distinguish academic productivity on the basis of academic rank, years posttraining, and neurosurgical subspecialties. ", "Overall, the authors conclude that the h index metric is a reasonable measure of academic productivity in the pediatric neurosurgery arena that provides a robust measure of an individual's contribution to the pediatric neurosurgery literature. ", "The h index calculation also reveals the productivity of the pediatric neurosurgeons to be on par with the productivity of neurosurgeons in general.", "The h-index frequency distribution conformed to both the log-linear variation of a power law (r (2) = .99) and the beta distribution with the same fitting exponents as previously described in a power law analysis of the productivity of neurosurgeons. ", "The h indices increased significantly with increasing academic rank, with the median for instructors, assistant professors, associate professors, and professors being 2, 5, 10, and 19, respectively (p < 0.0001, Kruskal-Wallis; all groups significantly different from each other except the difference between instructor and assistant professor [Conover]). Departmental chairs had a median h index of 22 (range 3-55) and program directors a median of 17 (range 0-62). Plot of the log of the rank versus h index demonstrated a remarkable linear pattern (R(2) = 0.995, p < 0.0001), suggesting that this is a power-law relationship.", "The distribution of the h index within an academic population is described for the first time and appears related to the ubiquitous power-law distribution.", "As expected, the h index increased with academic rank and there was a statistically significant difference between each rank. ", "Within the field of academic neurosurgery, clear differences of h indices between academic ranks exist. On average, an increase of the h index by 5 appears to correspond to the next highest academic rank, with the exception of chairperson.", "Scopus h-index was of borderline significance in predicting physician salary (P = 0.12). " ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/23820322", "http://www.ncbi.nlm.nih.gov/pubmed/23079075", "http://www.ncbi.nlm.nih.gov/pubmed/22381859", "http://www.ncbi.nlm.nih.gov/pubmed/19392590", "http://www.ncbi.nlm.nih.gov/pubmed/24055571", "http://www.ncbi.nlm.nih.gov/pubmed/21495810", "http://www.ncbi.nlm.nih.gov/pubmed/23886815", "http://www.ncbi.nlm.nih.gov/pubmed/22544537", "http://www.ncbi.nlm.nih.gov/pubmed/23870040", "http://www.ncbi.nlm.nih.gov/pubmed/24239737", "http://www.ncbi.nlm.nih.gov/pubmed/20380531", "http://www.ncbi.nlm.nih.gov/pubmed/23872122", "http://www.ncbi.nlm.nih.gov/pubmed/20469986" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D000043", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009493" ]

[ "Yes, bruxism is associated with reflux. Sleep bruxism is prevalent in GERD patients." ]

[ "yes" ]

[ "Sleep bruxism is prevalent in GERD patients, and GERD is highly associated with SB.", "There was a statistical trend towards tooth wear progression being associated with gastric risk factors (p < 0.05). ", "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. ", "The aim of this cross-over, randomized, single-blinded trial was to examine whether intra-esophageal acidification induces sleep bruxism (SB). ", "RMMA episodes including SB were induced by esophageal acidification. ", "Chronic regurgitation of gastric acids in patients with gastroesophageal reflux disease may cause dental erosion, which can lead in combination with attrition or bruxism to extensive loss of coronal tooth tissue.", "This clinical report describes treatment of severe tooth wear of a gastroesophageal reflux disease patient who is 54-year-old Turkish male patient. After his medical treatment, severe tooth wear, bruxism and decreased vertical dimensions were determined. ", "Gastroesophageal reflux disease by itself or in combination with attrition, abrasion or bruxism may be responsible for the loss.", "The association between bruxism, feeding and smoking habits and digestive disorders may lead to serious consequences to dental and related structures, involving dental alterations (wear, fractures and cracks), periodontal signs (gingival recession and tooth mobility) and muscle-joint sensitivity, demanding a multidisciplinary treatment plan. 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. ", "The frequencies of RMMA, single short-burst, and clenching episodes were significantly higher during decreased esophageal pH episodes than those during other times. ", "These results suggest that most jaw muscle activities, ie, RMMA, single short-burst, and clenching episodes, occur in relation to gastroesophageal reflux mainly in the supine position.", "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/22926484", "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/22156738", "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.ncbi.nlm.nih.gov/pubmed/841409" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D020186", "http://www.disease-ontology.org/api/metadata/DOID:2846", "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=D005764", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001244", "http://www.disease-ontology.org/api/metadata/DOID:8534" ]

[ "In prostate cancer patients, mindfulness interventions were well accepted and were effective in reducing stress, anxiety, avoidance, fear of cancer recurrence, cortisol levels and blood pressure, and improving quality of life, sleep quality and immune system functioning. In addition, mindfulness interventions promoted initiation of healthy dietary changes and decreases the rate of PSA increase and may slow the rate of tumor progression in cases of biochemically recurrent prostate cancer." ]

[]

[ "Participants reported regular mindfulness training practice, and there was a significant correlation between mindfulness training practice and changes in both initiation and maintenance of the change in A:V. These pilot results provide encouraging evidence for the feasibility of a dietary program that includes mindfulness training in supporting dietary change for men with recurrent prostate cancer and invite further study to explore the possible role of mindfulness training as a means of supporting both initiation of dietary changes and maintenance of those changes over time.", "FINDINGS: Following the 6-week MBSR program, patients showed improvements in stress and anxiety (p < .05); caregivers' psychological and QOL also improved but were not statistically significant. Both patients and caregivers had decreases in cortisol at Weeks 1 and 3 (p < .05) but not at Week 6. Similar to cortisol levels at Week 6, salivary interleukin-6 levels were lower overall (before/after an MBSR-C session), compared with Week 1 for patients and caregivers. CONCLUSIONS: MBSR-C may be a beneficial intervention for reducing stress, anxiety, cortisol levels, and symptoms in advanced-stage cancer patients and may also benefit caregivers.", "ESULTS: Significant improvements were observed for anxiety (p = 0.027), avoidance (p = 0.032), and mindfulness skills (p = 0.019), with a trend for a reduction in fear of cancer recurrence (p = 0.062).", "CONCLUSIONS: Mindfulness-based group interventions appear to have utility in this patient group and show promise for reducing anxiety, avoidance, and fear of cancer recurrence. ", " Linear mixed modeling showed significant improvements in overall symptoms of stress which were maintained over the follow-up period. Cortisol levels decreased systematically over the course of the follow-up. Immune patterns over the year supported a continued reduction in Th1 (pro-inflammatory) cytokines. Systolic blood pressure (SBP) decreased from pre- to post-intervention and HR was positively associated with self-reported symptoms of stress. CONCLUSIONS: MBSR program participation was associated with enhanced quality of life and decreased stress symptoms, altered cortisol and immune patterns consistent with less stress and mood disturbance, and decreased blood pressure. ", "Significant improvements were seen in overall quality of life, symptoms of stress, and sleep quality, but these improvements were not significantly correlated with the degree of program attendance or minutes of home practice. ", "CONCLUSIONS: MBSR program enrollment was associated with enhanced quality of life and decreased stress symptoms in breast and prostate cancer patients, and resulted in possibly beneficial changes in hypothalamic-pituitary-adrenal (HPA) axis functioning. ", "Significant improvements were seen in overall quality of life, symptoms of stress, and sleep quality. Although there were no significant changes in the overall number of lymphocytes or cell subsets, T cell production of IL-4 increased and IFN-gamma decreased, whereas NK cell production of IL-10 decreased.", "CONCLUSIONS: MBSR participation was associated with enhanced quality of life and decreased stress symptoms in breast and prostate cancer patients. This study is also the first to show changes in cancer-related cytokine production associated with program participation.", "CONCLUSIONS: Our small study provides evidence that a plant-based diet delivered in the context of MBSR decreases the rate of PSA increase and may slow the rate of tumor progression in cases of biochemically recurrent prostate cancer." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/16685074", "http://www.ncbi.nlm.nih.gov/pubmed/18400281", "http://www.ncbi.nlm.nih.gov/pubmed/22442202", "http://www.ncbi.nlm.nih.gov/pubmed/22853988", "http://www.ncbi.nlm.nih.gov/pubmed/7776900", "http://www.ncbi.nlm.nih.gov/pubmed/14749092", "http://www.ncbi.nlm.nih.gov/pubmed/23442556", "http://www.ncbi.nlm.nih.gov/pubmed/21625914", "http://www.ncbi.nlm.nih.gov/pubmed/17521871", "http://www.ncbi.nlm.nih.gov/pubmed/11696736", "http://www.ncbi.nlm.nih.gov/pubmed/12883107" ]

[]

[ "http://www.disease-ontology.org/api/metadata/DOID:10283", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D064866" ]

[ "There is still no national screening programme established in the UK. Prostate cancer screening of asymptomatic men is not recommended by the National Screening Council at present and is not encouraged in the NHS. However, PSA tests are being performed for prostate cancer screening. The CAP and ProtecT trials are aimed to evaluate prostate cancer screening in the UK." ]

[]

[ "Screening for early disease has been available for many years, but there is still no national screening programme established in the United Kingdom.", "Latest results from the UK trials evaluating prostate cancer screening and treatment: the CAP and ProtecT studies.", "The CAP and ProtecT trials (ISRCTN92187251 and ISRCTN20141217) will help resolve the prostate cancer screening debate, define the optimum treatment for localised disease and generate evidence to improve men's health.", "Increased usage of Prosdex leads to more informed decision making, the key aim of the UK Prostate Cancer Risk Management Programme. ", "To date, the AIDIT team has established a website to facilitate communication between project collaborators (www.impact-study.co.uk), has been represented at several international meetings and has facilitated a conference for the IMPACT study to bring together international research teams, clinicians and policy makers.", " This prospective questionnaire study was nested within the case-finding component of the ProtecT (prostate testing for cancer and treatment) feasibility study (ISRCTN20141297). ", "The UK NHS Executive has issued extensive guidance stressing the importance of adequate counselling prior to performing this test. ", "To examine the pattern of use of prostate-specific antigen (PSA) testing in a UK region, where National Health Service policy does not recommend screening for prostate cancer. ", "In all, 165 862 PSA tests were performed on 84 669 men, and over a third of men aged > or = 50 years had at least one PSA test. Men aged < 50 years accounted for 12.9% of first tests. The proportion of tests from primary care increased from 47.2% in 1993 to 67.0% in 1999. The mean age of men tested once decreased from 65.6 to 61.9 years (P trend < 0.001) and the proportion with an elevated PSA level also declined during the period. Repeat testing increased with PSA level (P < 0.001) but 29.4% of men with a PSA level of < or = 4 ng/mL also had repeat testing. Raised PSA values were more common from hospital than primary care (32.4% vs 20.6%, P < 0.001) and in older men. Test rates varied 100-fold across general practices, a finding not explained by sociodemographic factors, but one which reflects differential adherence to national guidelines, suggesting that general practitioners are key targets for attempting to rationalise the use of the PSA test. ", "These findings suggest that PSA screening is taking place against evidence-based advice and has resulted in over 20 000 men being designated as having a raised PSA level, creating a need for further assessment.", "There is no current prostate cancer screening programme in the UK. ", "Prostate cancer screening of asymptomatic men is not recommended by the National Screening Council at present and is not encouraged in the NHS.", "We used a nested case-control design on data from men in four prospective studies (from the UK, Maryland in the USA, and two from Finland) with available stored serum samples to determine whether there was an advantage in measuring both free prostate-specific antigen (PSA) and total PSA as a potential screening test for prostate cancer.", "Some respondents were reluctant to give the leaflet to people enquiring about screening for prostate cancer, for example, because they thought that the leaflet would cause anxiety, or because prostate cancer screening was not freely available locally. ", "National guidance (executive letter) EL(97)12 stated that population screening should not be provided by the NHS, or be offered to the public until there is effective screening technology for prostate cancer. ", "This postal questionnaire survey reveals that 81% (95% CI 75% to 87%) of responding general practitioners in North Staffordshire agreed with EL(97)12 and one in ten said that the executive letter changed their views, suggesting that such national guidance has an effect." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/20507844", "http://www.ncbi.nlm.nih.gov/pubmed/16720000", "http://www.ncbi.nlm.nih.gov/pubmed/12614245", "http://www.ncbi.nlm.nih.gov/pubmed/10185137", "http://www.ncbi.nlm.nih.gov/pubmed/21047592", "http://www.ncbi.nlm.nih.gov/pubmed/12587941", "http://www.ncbi.nlm.nih.gov/pubmed/10682690", "http://www.ncbi.nlm.nih.gov/pubmed/15049981", "http://www.ncbi.nlm.nih.gov/pubmed/15946386", "http://www.ncbi.nlm.nih.gov/pubmed/17309171", "http://www.ncbi.nlm.nih.gov/pubmed/19138385", "http://www.ncbi.nlm.nih.gov/pubmed/22952783", "http://www.ncbi.nlm.nih.gov/pubmed/16978272", "http://www.ncbi.nlm.nih.gov/pubmed/19021912", "http://www.ncbi.nlm.nih.gov/pubmed/11002455", "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=D008403", "http://www.disease-ontology.org/api/metadata/DOID:10283", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D055088", "http://www.disease-ontology.org/api/metadata/DOID:10286" ]