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[ "DOORS syndrome is a constellation of deafness, onychodystrophy, osteodystrophy, mental retardation, and seizures. It is a rare autosomal recessive disorder of unknown cause." ]

[ "deafness", "onychodystrophy", "osteodystrophy", "mental retardation", "seizures" ]

[ "Deafness, onychodystrophy, osteodystrophy, mental retardation, and seizures (DOORS) syndrome is a rare autosomal recessive disorder of unknown cause. ", "Through a search of available case studies and communication with collaborators, we identified families that included at least one individual with at least three of the five main features of the DOORS syndrome: deafness, onychodystrophy, osteodystrophy, intellectual disability, and seizures. " ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/24291220" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013568", "http://www.disease-ontology.org/api/metadata/DOID:225", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012816", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013577" ]

[ "Currently, two applications for NIPD of Down syndrome have been developed with potential and have displayed positive results; the NIPD using next-generation sequencing technologies and the NIPD using the methylated DNA immunoprecipitation (MeDIP) real-time quantitative polymerase chain reaction (qPCR). This study examined the methylation difference in AIRE and RASSF1A between maternal and placental DNA, and the implication of this difference in the identification of free fetal DNA in maternal plasma and in prenatal diagnosis of trisomy 21. Diagnosis of trisomy 21 was established according to the ratio of fetal-specific AIRE to RASSF1A in maternal plasma. Both methods confirmed that AIRE and RASSF1A were hypomethylated in maternal blood cells but hypermethylated in placental or chorionic villus tissues. It was concluded that hypermethylated AIRE and RASSF1A may serve as fetal-specific markers for the identification of fetal DNA in maternal plasma and may be used for noninvasive prenatal diagnosis of trisomy 21.", "This study examined the methylation difference in AIRE and RASSF1A between maternal and placental DNA, and the implication of this difference in the identification of free fetal DNA in maternal plasma and in prenatal diagnosis of trisomy 21. Similarly, cell-free fetal DNA can be reliably recovered from maternal plasma and assessed by quantitative PCR to detect fetal trisomy 21 and paternally derived single gene mutations. The presence of foetal DNA in the plasma of pregnant women has opened up new possibilities for non-invasive prenatal diagnosis. Moreover, the differential methylation for each locus could be seen during the whole pregnant period." ]

[]

[ "Potential of syncytiotrophoblasts isolated from the cervical mucus for early non-invasive prenatal diagnosis", "Maternal serum protein profile and immune response protein subunits as markers for non-invasive prenatal diagnosis of trisomy 21, 18, and 13", "Maternal serum protein profiling using proteomics may allow non-invasive diagnostic testing for the most common trisomies and may complement ultrasound-based methods to more accurately determine pregnancies with fetal aneuploidies", "The presence of foetal DNA in the plasma of pregnant women has opened up new possibilities for non-invasive prenatal diagnosis. The use of circulating foetal DNA for the non-invasive prenatal detection of foetal chromosomal aneuploidies is challenging as foetal DNA represents a minor fraction of maternal plasma DNA", "Using massively parallel sequencing, foetal trisomies 21, 13 and 18 have been detected from maternal plasma.", "These developments suggest that the analysis of foetal DNA in maternal plasma would play an increasingly important role in future obstetrics practice.", "Currently, two applications for NIPD of Down syndrome have been developed with potential and have displayed positive results; the NIPD using next-generation sequencing technologies and the NIPD using the methylated DNA immunoprecipitation (MeDIP) real-time quantitative polymerase chain reaction (qPCR)", "Cell-free fetal RNA was extracted from the plasma of peripheral blood from 121 women 9-20 weeks of pregnancy. Five single nucleotide polymorphism (SNP) loci in PLAC4 gene were analyzed by reverse transcriptase multiplex ligation-dependent probe amplification (RT-MLPA), followed by capillary electrophoresis", "Non-invasive prenatal diagnosis of trisomy 21 by dosage ratio of fetal chromosome-specific epigenetic markers in maternal plasma", "This study examined the methylation difference in AIRE and RASSF1A between maternal and placental DNA, and the implication of this difference in the identification of free fetal DNA in maternal plasma and in prenatal diagnosis of trisomy 21.", "Diagnosis of trisomy 21 was established according to the ratio of fetal-specific AIRE to RASSF1A in maternal plasma. Both methods confirmed that AIRE and RASSF1A were hypomethylated in maternal blood cells but hypermethylated in placental or chorionic villus tissues.", "It was concluded that hypermethylated AIRE and RASSF1A may serve as fetal-specific markers for the identification of fetal DNA in maternal plasma and may be used for noninvasive prenatal diagnosis of trisomy 21.", "Preliminary reports indicate that the detection of fetal aneuploidies might be possible using epigenetically modified genes, e.g. maspin on chromosome 18. Additionally, an exiting recent development is that it might be feasible to detect Down syndrome via the quantitative assessment of placentally derived cell-free mRNA of chromosome-21-specific genes such as PLAC4", "Candidate epigenetic biomarkers for non-invasive prenatal diagnosis of Down syndrome", "Next, it was shown that the methylation status of chorionic villus sample DNA from first trimester pregnancies matched the hypermethylated state of term placenta.", "Non-invasive prenatal diagnosis of trisomy 21 by reverse transcriptase multiplex ligation-dependent probe amplification.", "To study whether pregnant women would like to be informed if sex chromosomal abnormalities (SCA) were suspected with the non-invasive prenatal diagnosis of fetal Down syndrome (the NIFTY) test." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/25218787", "http://www.ncbi.nlm.nih.gov/pubmed/22500647", "http://www.ncbi.nlm.nih.gov/pubmed/22839575", "http://www.ncbi.nlm.nih.gov/pubmed/18207470", "http://www.ncbi.nlm.nih.gov/pubmed/12498419", "http://www.ncbi.nlm.nih.gov/pubmed/21303301", "http://www.ncbi.nlm.nih.gov/pubmed/22038362", "http://www.ncbi.nlm.nih.gov/pubmed/17697502", "http://www.ncbi.nlm.nih.gov/pubmed/23371439", "http://www.ncbi.nlm.nih.gov/pubmed/22773950" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004314", "http://www.disease-ontology.org/api/metadata/DOID:14250", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011296" ]

[ "H3K4me3 is associated with transcriptionally active genes, but its function in the transcription process is still unclear. It is well known to occur in the promoter region of genes for transcription activation but its levels correlate positively with the antisense expression levels of the associated sense genes implying that it may be also involved in the activation of antisense transcription. Although it is mostly associated with transcription initiation H3K4me3 levels determine the efficiency of transcription elongation." ]

[ "transcriptional initiation" ]

[ "The histone marks appeared mainly in generic regions and were enriched around the transcription start sites (TSSs) of genes", "Trimethylation of histone H3 Lys 4 (H3K4me3) is a mark of active and poised promoters.", "Histone H3 lysine 4 trimethylation (H3K4me3) is well known to occur in the promoter region of genes for transcription activation", "3'-H3K4me3 is associated with ~15% of protein-coding genes in both tissues", "Furthermore, 3'-H3K4me3 modification levels correlate positively with the antisense expression levels of the associated sense genes, implying that 3'-H3K4me3 is involved in the activation of antisense transcription.", "Among these are forms of histone 3 that are mono- or tri-methylated at lysine 4 (H3K4me1 or H3K4me3, respectively), which bind preferentially to promoter and enhancer elements in the mammalian genome", "we find that H3K4me1 and H3K4me3 are enriched at transcriptional start sites in the genome", "H3K4me1 and H3K4me3 generally mark cis regulatory elements" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/22855832", "http://www.ncbi.nlm.nih.gov/pubmed/21435340", "http://www.ncbi.nlm.nih.gov/pubmed/22132139", "http://www.ncbi.nlm.nih.gov/pubmed/23284292", "http://www.ncbi.nlm.nih.gov/pubmed/22768981", "http://www.ncbi.nlm.nih.gov/pubmed/22904080", "http://www.ncbi.nlm.nih.gov/pubmed/18682226", "http://www.ncbi.nlm.nih.gov/pubmed/23355544" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D035165", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D020871", "http://www.biosemantics.org/jochem#4250488", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D042925", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D050436", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D051697", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D051758", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D035582", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D048348", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D061805", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D015533", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D035181", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D035581" ]

[ "PABP4 binds mRNA poly(A) tails." ]

[ "PABP4 binds mRNA poly(A) tails." ]

[ "RNA binding proteome", "In vertebrates, poly(A) binding protein (PABP) is known to exist in five different isoforms.", "Cytoplasmic poly(A)-binding proteins (PABPs) regulate mRNA stability and translation. ", " poly(A) binding proteins 1 and 4 (PABPC1 and PABPC4)", "Cytoplasmic poly(A) binding protein 4 (PABPC4) is an RNA-processing protein that plays an important role in the regulation of gene expression.", "Cytoplasmic poly(A) binding protein 4 ", "poly(A)-binding protein (PABP) ", "Poly(A) binding protein (PABP) binds mRNA poly(A) tails ", "Using mass spectrometry sequencing we identified poly(A) binding proteins-1 and -4 (PABP1 and PABP4) ", "The poly(A)-binding protein (PABP) is an important translation initiation factor that binds to the polyadenylated 3' end of mRNA.", "A family of cytoplasmic poly(A)-binding proteins (PABPs) bind the poly(A) tail and can regulate mRNA translation and stability. ", "Human PABP binds AU-rich RNA via RNA-binding domains 3 and 4." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/23938467", "http://www.ncbi.nlm.nih.gov/pubmed/18467502", "http://www.ncbi.nlm.nih.gov/pubmed/21518916", "http://www.ncbi.nlm.nih.gov/pubmed/22884093", "http://www.ncbi.nlm.nih.gov/pubmed/23300856", "http://www.ncbi.nlm.nih.gov/pubmed/14717712", "http://www.ncbi.nlm.nih.gov/pubmed/21940797", "http://www.ncbi.nlm.nih.gov/pubmed/18753244", "http://www.ncbi.nlm.nih.gov/pubmed/20943973", "http://www.ncbi.nlm.nih.gov/pubmed/22896784", "http://www.ncbi.nlm.nih.gov/pubmed/15676026" ]

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"http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A2373607", "o": "inducible PABP, human" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A2374397", "o": "poly(A)-binding protein, cytoplasmic 4 (inducible form), human" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A3831853", "o": "PABPC4 protein, human" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C0536210", "o": "http://linkedlifedata.com/resource/umls/label/A2374397" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A3839562", "o": "activated-platelet protein-1, human" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A3845291", "o": "APP-1 protein, human" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C0536210", "o": "http://linkedlifedata.com/resource/umls/label/A8596234" }, { "p": "http://linkedlifedata.com/resource/umls/prefMetaMap", "s": "http://linkedlifedata.com/resource/umls/id/C0536210", "o": "http://linkedlifedata.com/resource/umls/label/A3831853" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C0536210", "o": "http://linkedlifedata.com/resource/umls/label/A3831883" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C0536210", "o": "http://linkedlifedata.com/resource/umls/label/A2373607" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A2373587", "o": "iPABP protein, human" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A8596234", "o": "PABP4 protein, human" }, { "p": "http://linkedlifedata.com/resource/umls/altMetaMap", "s": "http://linkedlifedata.com/resource/umls/id/C0536210", "o": "http://linkedlifedata.com/resource/umls/label/A8606969" }, { "p": "http://linkedlifedata.com/resource/umls/altMetaMap", "s": "http://linkedlifedata.com/resource/umls/id/C0536210", "o": "http://linkedlifedata.com/resource/umls/label/A8596234" }, { "p": "http://linkedlifedata.com/resource/umls/altMetaMap", "s": "http://linkedlifedata.com/resource/umls/id/C0536210", "o": "http://linkedlifedata.com/resource/umls/label/A3845291" }, { "p": "http://www.w3.org/2008/05/skos-xl#altLabel", "s": "http://linkedlifedata.com/resource/umls/id/C0536210", "o": "http://linkedlifedata.com/resource/umls/label/A3839562" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A2373607", "o": "C104581" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": 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[ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0006378", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D026723", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0005515", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011061", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0043631", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011485", "http://www.uniprot.org/uniprot/PABP4_HUMAN", "http://www.biosemantics.org/jochem#4249823", "http://www.uniprot.org/uniprot/PABP_DROME", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0008143", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D039221" ]

[ "Intermediate filaments have an average diameter of 10 nanometers (nm)." ]

[ "10 nanometers", "10 nm" ]

[ "Negative staining showed that supernatants from the centrifugation assays contained protofilaments, protofibrils and short particles (less than 300 nm), but pellets contained long filaments (greater than 1 micron) with an average diameter of 10 nm.", "Ultrastructurally, rhabdoid cells showed paranuclear aggregates and whorls of intermediate filaments with a 9-10 nm diameter.", "After removing IFs by calcination, electron microscopy revealed hollow silica nanotubes several micrometers long, with outer diameters of 35-55 nm and an average inner diameter of 10 nm (comparable to that of IFs)", "Intermediate filaments are filaments 10 nm in diameter that make up an important component of the cytoskeleton in most metazoan taxa.", "Neurofilaments (NFs) are essential cytoskeletal filaments that impart mechanical integrity to nerve cells. They are assembled from three distinct molecular mass proteins that bind to each other to form a 10-nm-diameter filamentous rod with sidearm extensions.", "Scanning tunneling microscope (STM) and transmission electron microscope (TEM) micrographs showed that acidic keratins and basic keratins can assemble into dimers and further into 10 nm filamentsin vitro.", "Intermediate in diameter between microtubules and microfilaments, IFs constitute the third cytoskeletal filament system of metazoan cells.", "Just above the bulb, the filaments are characterized by a diameter of 100 Angstroms and a low-density core.", "Further, using cryo-transmission electron microscopy on native, fully hydrated, vitreous epidermis we show that the subfilametous keratin electron density pattern consists, both in corneocytes and in viable keratinocytes, of one axial subfilament surrounded by an undetermined number of peripheral subfilaments forming filaments with a diameter of approximately 8 nm." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/18523546", "http://www.ncbi.nlm.nih.gov/pubmed/17289402", "http://www.ncbi.nlm.nih.gov/pubmed/22126386", "http://www.ncbi.nlm.nih.gov/pubmed/22848616", "http://www.ncbi.nlm.nih.gov/pubmed/18726512", "http://www.ncbi.nlm.nih.gov/pubmed/15373777", "http://www.ncbi.nlm.nih.gov/pubmed/19559031", "http://www.ncbi.nlm.nih.gov/pubmed/19656809", "http://www.ncbi.nlm.nih.gov/pubmed/21669844", "http://www.ncbi.nlm.nih.gov/pubmed/2264817", "http://www.ncbi.nlm.nih.gov/pubmed/16458019" ]

[ { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A0059267", "o": "Filaments, Intermediate" } ]

[ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D007382" ]

[ "Genomic regulatory blocks (GRBs) are chromosomal regions spanned by highly conserved non-coding elements (HCNEs), most of which serve as regulatory inputs of one target gene in the region. The target genes are most often transcription factors involved in embryonic development and differentiation. GRBs often contain extensive gene deserts, as well as additional 'bystander' genes intertwined with HCNEs but whose expression and function are unrelated to those of the target gene. GRB target genes have properties that set them apart from their bystanders as well as other genes in the genome: longer CpG islands, a higher number and wider spacing of alternative transcription start sites, and a distinct composition of transcription factor binding sites in their core/proximal promoters. Target gene expression correlates with the acetylation state of HCNEs in the region." ]

[]

[ "Recent functional studies have demonstrated that many microRNAs (miRNAs) are expressed by RNA polymerase II in a specific spatiotemporal manner during the development of organisms and play a key role in cell-lineage decisions and morphogenesis. They are therefore functionally related to a number of key protein coding developmental genes, that form genomic regulatory blocks (GRBs) with arrays of highly conserved non-coding elements (HCNEs) functioning as long-range enhancers that collaboratively regulate the expression of their target genes", "Genomic regulatory blocks (GRBs) are chromosomal regions spanned by highly conserved non-coding elements (HCNEs), most of which serve as regulatory inputs of one target gene in the region. The target genes are most often transcription factors involved in embryonic development and differentiation. GRBs often contain extensive gene deserts, as well as additional 'bystander' genes intertwined with HCNEs but whose expression and function are unrelated to those of the target gene.", "We show evidence that GRB target genes have properties that set them apart from their bystanders as well as other genes in the genome: longer CpG islands, a higher number and wider spacing of alternative transcription start sites, and a distinct composition of transcription factor binding sites in their core/proximal promoters. Target gene expression correlates with the acetylation state of HCNEs in the region", "GRB targets are genes with a number of unique features that are the likely cause of their ability to respond to regulatory inputs from very long distances.", "Insect genomes contain larger blocks of conserved gene order (microsynteny) than would be expected under a random breakage model of chromosome evolution. We present evidence that microsynteny has been retained to keep large arrays of highly conserved noncoding elements (HCNEs) intact. These arrays span key developmental regulatory genes, forming genomic regulatory blocks (GRBs). We recently described GRBs in vertebrates, where most HCNEs function as enhancers and HCNE arrays specify complex expression programs of their target genes.", "We found the largest mammal-teleost conserved chromosomal segments to be spanned by highly conserved noncoding elements (HCNEs), their developmental regulatory target genes, and phylogenetically and functionally unrelated \"bystander\" genes. Bystander genes are not specifically under the control of the regulatory elements that drive the target genes and are expressed in patterns that are different from those of the target genes", "Genomic regulatory blocks (GRBs) are chromosomal regions spanned by highly conserved non-coding elements (HCNEs), most of which serve as regulatory inputs of one target gene in the region.", "BACKGROUND: Genomic regulatory blocks (GRBs) are chromosomal regions spanned by highly conserved non-coding elements (HCNEs), most of which serve as regulatory inputs of one target gene in the region. The target genes are most often transcription factors involved in embryonic development and differentiation. ", "GRBs often contain extensive gene deserts, as well as additional 'bystander' genes intertwined with HCNEs but whose expression and function are unrelated to those of the target gene. The tight regulation of target genes, complex arrangement of regulatory inputs, and the differential responsiveness of genes in the region call for the examination of fundamental rules governing transcriptional activity in GRBs. ", "Genomic regulatory blocks (GRBs) are chromosomal regions spanned by highly conserved non-coding elements (HCNEs), most of which serve as regulatory inputs of one target gene in the region. The target genes are most often transcription factors involved in embryonic development and differentiation." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/19969543", "http://www.ncbi.nlm.nih.gov/pubmed/17387144", "http://www.ncbi.nlm.nih.gov/pubmed/17989259", "http://www.ncbi.nlm.nih.gov/pubmed/21619633", "http://www.ncbi.nlm.nih.gov/pubmed/19374772" ]

[ { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A0027269", "o": "D001244" }, { "p": "http://www.w3.org/2004/02/skos/core#notation", "s": "http://linkedlifedata.com/resource/umls/label/A0027288", "o": "D001244" } ]

[ "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=D005809", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D053263" ]

[ "The main bulk of experimental pharmacological interventions addressing the clinical problem of frailty have been focused on the use of hormones, as replacement therapy in subjects with low or normal circulating basal levels of the hormone. Results have been disappointing, except for the case of testosterone that have shown some benefits. The effectiveness of other potential therapeutic interventions (antioxidants, anti-inflammatory agents, nutritional supplements) appears to be limited or has not been explored in detail until now." ]

[]

[ "The main bulk of experimental pharmacological interventions addressing the clinical problem of frailty have been focused on the use of hormones, as replacement therapy in subjects with low or normal circulating basal levels of the hormone. Results have been disappointing, except for the case of testosterone that have shown some benefits. The effectiveness of other potential therapeutic interventions (antioxidants, anti-inflammatory agents, nutritional supplements) appears to be limited or has not been explored in detail until now.", "effective treatment options are still under investigation.", "Design of therapeutic interventions for geriatric frailty has been challenging and may be because of inadequate understanding of its biological underpinnings" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/20852673", "http://www.ncbi.nlm.nih.gov/pubmed/20223299", "http://www.ncbi.nlm.nih.gov/pubmed/24079768" ]

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"http://data.linkedct.org/resource/linkedct/condition", "s": "http://data.linkedct.org/resource/trials/NCT00190060", "o": "http://data.linkedct.org/resource/condition/11756" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://data.linkedct.org/resource/trials/NCT00190060", "o": "Trial NCT00190060" }, { "p": "http://data.linkedct.org/resource/linkedct/condition", "s": "http://data.linkedct.org/resource/trials/NCT00465153", "o": "http://data.linkedct.org/resource/condition/11756" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://data.linkedct.org/resource/trials/NCT00465153", "o": "Trial NCT00465153" }, { "p": "http://data.linkedct.org/resource/linkedct/condition", "s": "http://data.linkedct.org/resource/trials/NCT00744094", "o": "http://data.linkedct.org/resource/condition/11756" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://data.linkedct.org/resource/trials/NCT00744094", "o": "Trial NCT00744094" }, { "p": 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[ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016033", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D055948" ]

[ "Hutchinson-Gilford progeria syndrome is a rare, sporadic, autosomal dominant syndrome that involves premature aging, generally leading to death at approximately 13 years of age due to myocardial infarction or stroke. \tThe genetic basis of most cases of this syndrome is a change from glycine GGC to glycine GGT in codon 608 of the lamin A (LMNA) gene, which activates a cryptic splice donor site to produce abnormal lamin A; this disrupts the nuclear membrane and alters transcription." ]

[]

[ "Hutchinson-Gilford progeria syndrome is a syndrome that involves premature aging, leading usually to death at the age between 10 to 14 years predominatly due to a myocardial infarction or a stroke", "The genetic basis in most cases is a mutation at the nucleotide position 1824 of the lamin A gene", "At this position, cytosine is substituted for thymine so that a cryptic splice site within the precursor mRNA for lamin A is generated. This results in a production of abnormal lamin A, termed progerin", "Hutchinson-Gilford progeria syndrome is a rare, sporadic, autosomal dominant syndrome that involves premature aging, generally leading to death at approximately 13 years of age due to myocardial infarction or stroke", "The genetic basis of most cases of this syndrome is a change from glycine GGC to glycine GGT in codon 608 of the lamin A (LMNA) gene, which activates a cryptic splice donor site to produce abnormal lamin A; this disrupts the nuclear membrane and alters transcription" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/24019745", "http://www.ncbi.nlm.nih.gov/pubmed/17677003", "http://www.ncbi.nlm.nih.gov/pubmed/2687104", "http://www.ncbi.nlm.nih.gov/pubmed/6214719", "http://www.ncbi.nlm.nih.gov/pubmed/21217880", "http://www.ncbi.nlm.nih.gov/pubmed/18256394", "http://www.ncbi.nlm.nih.gov/pubmed/9309268", "http://www.ncbi.nlm.nih.gov/pubmed/1128606" ]

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[ "http://www.disease-ontology.org/api/metadata/DOID:37", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D014898", "http://www.disease-ontology.org/api/metadata/DOID:0050325", "http://www.disease-ontology.org/api/metadata/DOID:3911", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011371", "http://www.disease-ontology.org/api/metadata/DOID:0050739", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D003057", "http://www.disease-ontology.org/api/metadata/DOID:5688", "http://www.disease-ontology.org/api/metadata/DOID:630" ]

[ "Cryptochrome-1 (Cry1) is an essential component of the central and peripheral circadian clocks for generation of circadian rhythms in mice." ]

[ "component of the central and peripheral circadian clocks for generation of circadian rhythms in mice" ]

[ "Malfunction of the circadian clock has been linked to the pathogenesis of a variety of diseases. We show that mice lacking the core clock components Cryptochrome-1 (Cry1) and Cryptochrome-2 (Cry2) (Cry-null mice) show salt-sensitive hypertension due to abnormally high synthesis of the mineralocorticoid aldosterone by the adrenal gland.", "The Cryptochrome 1 and 2 genes are indispensable for molecular core oscillator function, as evident from the arrhythmic wheel-running behavior and lack of rhythmic clock gene expression in mCry1/mCry2 double-mutant mice in constant darkness.", "Among the components driving the mammalian circadian clock are the Period 1 and 2 (mPer1 and mPer2) and Cryptochrome 1 and 2 (mCry1 and mCry2) genes. A mutation in the mPer2 gene leads to a gradual loss of circadian rhythmicity in mice kept in constant darkness (DD). Here we show that inactivation of the mCry2 gene in mPer2 mutant mice restores circadian rhythmicity and normal clock gene expression patterns. Thus, mCry2 can act as a nonallelic suppressor of mPer2, which points to direct or indirect interactions of PER2 and CRY2 proteins. In marked contrast, inactivation of mCry1 in mPer2 mutant mice does not restore circadian rhythmicity but instead results in complete behavioral arrhythmicity in DD, indicating different effects of mCry1 and mCry2 in the clock mechanism", "Cryptochrome 1 and 2 gene products act in the negative feedback loop and are indispensable for molecular core oscillator function, as evident from the arrhythmic wheel running behaviour and absence of cyclic clock gene expression in mCry1/mCry2 double mutant mice in constant darkness.", ", when mCry-deficient mice are housed in normal light-dark cycles, a single non-circadian peak in neuronal activity can be detected in SCN slices prepared two hours after the beginning of the day. This light-induced increase in electric activity of the SCN suggests that deletion of the mCry genes converts the core oscillator in an hour-glass-like timekeeper and may explain why in normal day-night cycles mCry-deficient mice show apparently normal behaviour.", "Cryptochrome 1 and 2 act as essential components of the central and peripheral circadian clocks for generation of circadian rhythms in mammals", "cryptochrome-1 mRNA was found in DA cells, immunocytochemistry was extended to other components of the circadian clock machinery. This analysis showed that DA cells contain the most common clock-related proteins.", "Cryptochrome 1 and cryptochrome 2 proteins are core components of the mammalian circadian clock and mice mutated in both genes are arrhythmic.", "a domain in the extreme C terminus of BMAL1 that plays an essential role in the rhythmic control of E-box-mediated circadian transcription. Remarkably, the last 43 aa of BMAL1 are required for transcriptional activation, as well as for association with the circadian transcriptional repressor CRYPTOCHROME 1 (CRY1), depending on the coexistence of CLOCK protein.", "circadian rhythm protein cryptochrome 1 (CRY1).", "CRY1 is a master regulator of circadian rhythm that regulates the extracellular calcification of MSCs.", "Studying mouse fibroblasts, we demonstrated that the nutrient-responsive adenosine monophosphate-activated protein kinase (AMPK) phosphorylates and destabilizes the clock component cryptochrome 1 (CRY1). In mouse livers, AMPK activity and nuclear localization were rhythmic and inversely correlated with CRY1 nuclear protein abundance. Stimulation of AMPK destabilized cryptochromes and altered circadian rhythms, and mice in which the AMPK pathway was genetically disrupted showed alterations in peripheral clocks. Thus, phosphorylation by AMPK enables cryptochrome to transduce nutrient signals to circadian clocks in mammalian peripheral organs.", "Cytoplasmic hnRNP D levels displayed a pattern that was reciprocal to the mcry1 oscillation. Knockdown of hnRNP D stabilized mcry1 mRNA and resulted in enhancement of the oscillation amplitude and a slight delay of the phase. Our results suggest that hnRNP D plays a role as a fine regulator contributing to the mcry1 mRNA turnover rate and the modulation of circadian rhythm.", "more than three mutations of conserved PER2 residues impaired not only binding to CRY1 but also subsequent nuclear translocation, although mutations of non-conserved residues did not affect interaction with CRY1. Thus, the conserved amino acid residues of 1179-1198 in PER2 are apparently responsible for binding to CRY1.", "Cryptochrome 1 and 2 (Cry1 and Cry2) are considered essential for generating circadian rhythms in mammals. The role of Cry1 and Cry2 in circadian rhythm expression and acute light-induced suppression of pineal melatonin was assessed using Cry1 and Cry2 double-deficient mice (Cry1(-/-) /Cry2(-/-) ) developed from the C3H strain that synthesizes melatonin.", "Cryptochrome 1 (Cry1), an essential clock component, displays evening-time expression and serves as a strong repressor at morning-time elements (E box/E' box).", "A genetic complementation assay in Cry1(-/-):Cry2(-/-) cells revealed that substantial delay of Cry1 expression is required to restore circadian rhythmicity, and its prolonged delay slows circadian oscillation. Taken together, our data suggest that phase delay in Cry1 transcription is required for mammalian clock function.", "the 24-h mRNA rhythms of the following genes were suppressed in db/db mice compared with control mice: the clock genes period homolog 1/2 (Per1/2) and cryptochrome 1/2 (Cry1/2) and their target genes D site albumin promoter-binding protein (Dbp) and peroxisome proliferator-activated receptor-γ (Pparg) in the aorta and mesenteric arteries; Dbp in the heart; Per1, nuclear receptor subfamily 1, group D, member 1 (Rev-erba), and Dbp in the kidney; and Per1 in the suprachiasmatic nucleus.", "In mammals, circadian rhythms in behavior and physiology are controlled by a central pacemaker, the SCN, and subordinated clocks throughout the body. On the molecular level, these clocks are based on transcriptional/translational feedback loops involving a set of clock genes that regulate their own transcription. Among the components driving the mammalian circadian clock are the Period 1 and 2 (Per1 and Per2) and Cryptochrome 1 and 2 (Cry1 and Cry2) genes. I", "The mammalian clock protein, cryptochrome 1 (CRY1), is degraded via the FBXL3-mediated ubiquitination pathway, suggesting that it is also likely to be targeted by the deubiquitination pathway. Here, we identified that USP2a, a circadian-controlled deubiquitinating enzyme, interacts with CRY1 and enhances its protein stability via deubiquitination upon serum shock. Depletion of Usp2a by shRNA greatly enhances the ubiquitination of CRY1 and dampens the oscillation amplitude of the CRY1 protein during a circadian cycle. By stabilizing the CRY1 protein, USP2a represses the Per2 promoter activity as well as the endogenous Per2 gene expression. We also demonstrated that USP2a-dependent deubiquitination and stabilization of the CRY1 protein occur in the mouse liver.", "The mammalian circadian clock is composed of interlocking feedback loops. Cryptochrome is a central component in the core negative feedback loop, whereas Rev-Erbα, a member of the nuclear receptor family, is an essential component of the interlocking loop.", "By analyzing the Fbxl3 and Cryptochrome 1 double-mutant mice, we found that FBXL3 also regulates the amplitudes of E-box-driven gene expression. These two separate roles of FBXL3 in circadian feedback loops provide a mechanism that contributes to the period determination and robustness of the clock." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/19858287", "http://www.ncbi.nlm.nih.gov/pubmed/16731656", "http://www.ncbi.nlm.nih.gov/pubmed/12381662", "http://www.ncbi.nlm.nih.gov/pubmed/16061665", "http://www.ncbi.nlm.nih.gov/pubmed/19833968", "http://www.ncbi.nlm.nih.gov/pubmed/12495442", "http://www.ncbi.nlm.nih.gov/pubmed/15047890", "http://www.ncbi.nlm.nih.gov/pubmed/23471982", "http://www.ncbi.nlm.nih.gov/pubmed/16777965", "http://www.ncbi.nlm.nih.gov/pubmed/21236481", "http://www.ncbi.nlm.nih.gov/pubmed/19405859", "http://www.ncbi.nlm.nih.gov/pubmed/22952936", "http://www.ncbi.nlm.nih.gov/pubmed/22140039", "http://www.ncbi.nlm.nih.gov/pubmed/22170608", "http://www.ncbi.nlm.nih.gov/pubmed/18974860", "http://www.ncbi.nlm.nih.gov/pubmed/20100521", "http://www.ncbi.nlm.nih.gov/pubmed/15980066", "http://www.ncbi.nlm.nih.gov/pubmed/20825493", "http://www.ncbi.nlm.nih.gov/pubmed/12121621", "http://www.ncbi.nlm.nih.gov/pubmed/20023637", "http://www.ncbi.nlm.nih.gov/pubmed/22669941", "http://www.ncbi.nlm.nih.gov/pubmed/14712914" ]

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[]

[ "The July effect is the hypothetical increase in morbidity and mortality thought to be associated with the influx of new (or newly promoted) trainees during the first portion of the academic year (in July)." ]

[]

[ "It is unclear, however, if this difference was related to climatological changes or inexperienced medical trainees (the July effect). ", " Given the nonteaching nature of these hospitals, the findings demonstrate that increases in the rate of SSI during the summer are more likely related to ecological and/or environmental factors than the July effect.", "BACKGROUND: Lower quality of care and poorer outcomes are suspected when new trainees (eg, residents) start in July in teaching hospitals, the so-called \"the July effect.\"", "The \"August\" or \"July effect\" describes increased errors and reduced patient safety during this transition. ", "PURPOSE: Researchers have found mixed results about the risk to patient safety in July, when newly minted physicians enter U.S. hospitals to begin their clinical training, the so-called \"July effect.\"", "INTRODUCTION: There has been concern of increased emergency department (ED) length of stay (LOS) during the months when new residents are orienting to their roles. This so-called \"July Effect\" has long been thought to increase LOS, and potentially contribute to hospital overcrowding and increased waiting time for patients.", "SUMMARY OF BACKGROUND DATA: The July effect is the hypothetical increase in morbidity and mortality thought to be associated with the influx of new (or newly promoted) trainees during the first portion of the academic year.", "Studies of whether inpatient mortality in US teaching hospitals rises in July as a result of organizational disruption and relative inexperience of new physicians (July effect) find small and mixed results, perhaps because study populations primarily include low-risk inpatients whose mortality outcomes are unlikely to exhibit a July effect.", "Elderly hip fracture patients treated at teaching hospitals had 12% greater relative risk of mortality in July/August (ie, experience a \"July effect\") compared with nonteaching hospitals during that time period (1998-2003).", "Many have suggested that these new medical residents may produce errors and worsen patient outcomes-the so-called \"July Effect;\" however, we have found no U.S. evidence documenting this effect.", "A "July effect" of increased complications when new trainees begin residency has been reported widely by the media.", "The July Effect thus contributed to only a 2.4% higher FTOR in teaching hospitals compared to 19% in non teaching hospitals. The July Effect is reflective of an overall increase in morbidity in all hospitals at the beginning of the academic cycle and it had a pronounced effect in non-teaching hospitals.", "Studies of whether inpatient mortality in US teaching hospitals rises in July as a result of organizational disruption and relative inexperience of new physicians (July effect) find small and mixed results, perhaps because study populations primarily include low-risk inpatients whose mortality outcomes are unlikely to exhibit a July effect." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/20145785", "http://www.ncbi.nlm.nih.gov/pubmed/24152859", "http://www.ncbi.nlm.nih.gov/pubmed/25633735", "http://www.ncbi.nlm.nih.gov/pubmed/20512532", "http://www.ncbi.nlm.nih.gov/pubmed/24578770", "http://www.ncbi.nlm.nih.gov/pubmed/25374038", "http://www.ncbi.nlm.nih.gov/pubmed/23737378", "http://www.ncbi.nlm.nih.gov/pubmed/25542761", "http://www.ncbi.nlm.nih.gov/pubmed/24384663", "http://www.ncbi.nlm.nih.gov/pubmed/25860519", "http://www.ncbi.nlm.nih.gov/pubmed/24059450" ]

[]

[]

[ "Nestin can be used as a nonspecific marker protein for precursor cells in the subventricular zone (SVZ). Nestin is a unique intermediate filament protein. While it is robustly expressed in developing brain, postnatal expression is limited to the brain's SVZ." ]

[ "Nestin" ]

[ "Nestin is a unique intermediate filament protein. While it is robustly expressed in developing brain, postnatal expression is limited to the brain's subventricular zone (SVZ)", "nestin, a marker protein for precursor cells in the subventricular zone", "adult subventricular zone (SVZ) stem and progenitor cells express nestin", "the typical protein of neural progenitors, nestin", "the nonspecific precursor cell marker Nestin", "In the subventricular zone, this effect was exerted selectively on a precursor subpopulation expressing nestin but not neuronal or glial cell-specific proteins.", "Nestin is an intermediate filament protein expressed in neuroepithelial stem cells during development and it is later replaced by cell specific neuronal or glial filaments.", "The results indicate that administration of thyroid hormone and retinoic acid increases the expression of Ki67, a nuclear antigen associated with cell proliferation, and of nestin, a marker protein for precursor cells in the subventricular zone of adult male rats.", "Only a minority of stem cells expressed nestin, a marker for neural precursor cells.", "In addition, bone marrow transplantation promoted proliferation of ependymal and subependymal cells, identified by nestin (a neuroepithelial stem cell marker), within the ventricular zone and subventricular zone (VZ/SVZ).", "The results indicate that administration of thyroid hormone and retinoic acid increases the expression of Ki67, a nuclear antigen associated with cell proliferation, and of nestin, a marker protein for precursor cells in the subventricular zone of adult male rats", "In all animals, 20-40% of the newly generated cells in the dentate gyrus and subventricular zone expressed the neural progenitor cell markers Musashi1 or Nestin" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/21527990", "http://www.ncbi.nlm.nih.gov/pubmed/23131160", "http://www.ncbi.nlm.nih.gov/pubmed/20552272", "http://www.ncbi.nlm.nih.gov/pubmed/15458607", "http://www.ncbi.nlm.nih.gov/pubmed/16567040", "http://www.ncbi.nlm.nih.gov/pubmed/16647786", "http://www.ncbi.nlm.nih.gov/pubmed/17717696", "http://www.ncbi.nlm.nih.gov/pubmed/11294470", "http://www.ncbi.nlm.nih.gov/pubmed/22027098", "http://www.ncbi.nlm.nih.gov/pubmed/10802345", "http://www.ncbi.nlm.nih.gov/pubmed/15056462", "http://www.ncbi.nlm.nih.gov/pubmed/11078926", "http://www.ncbi.nlm.nih.gov/pubmed/23407958", "http://www.ncbi.nlm.nih.gov/pubmed/14715941", "http://www.ncbi.nlm.nih.gov/pubmed/12812760" ]

[]

[ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0005882", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0021849" ]

[ "The mammalian DNA (cytosine-5) methyltransferase 1, DNMT1 is the major enzyme responsible for the maintenance of the DNA methylation patterns on the newly synthesized strand after DNA replication. DNMT1 prefers hemimethylated DNA and during DNA replication methylates hemimethylated CpG sites by copying methylation patterns from the parental DNA strand to the newly synthesized daughter strand. The equivalent of DNMT1 in plants is MET1." ]

[ "DNMT1", "MET1" ]

[ "his defect does not appear in mouse models with mutations in Dnmt3a and Mthfr genes and, therefore, it is specific for the Dnmt1 gene and is suggestive of a role of DNMT1 in imprint resetting or maintenance in the male germ line.", "Specificity of Dnmt1 for methylation of hemimethylated CpG sites resides in its catalytic domain.", "We obtained evidence that some 5-methylcytosine residues in these single-stranded DNAs can stimulate de novo methylation of adjacent sites by murine DNA 5-cytosine methyltransferase as effectively as 5-methylcytosine residues in double-stranded DNA stimulate maintenance methylation.", "We present in vitro evidence that the mammalian de novo DNA methyltransferases DNMT3A and DNMT3B, but not the maintenance enzyme DNMT1, are also redox-dependent DNA dehydroxymethylases.", "Direct comparison to met1 plants, deficient in maintenance methyltransferase MET1, showed higher sensitivity of ddm1 plants to NaCl.", "DNMT1, the major maintenance DNA methyltransferase in animals, helps to regulate gene expression, genome imprinting, and X-chromosome inactivation.", "Correct establishment and maintenance of methylation patterns at imprinted genes has been associated with placental function and regulation of embryonic/fetal development.", "Contributions of CTCF and DNA methyltransferases DNMT1 and DNMT3B to Epstein-Barr virus restricted latency.", "Thus, differential expression of CTCF and DNMT1 and -3B is not critical for maintenance of restricted latency.", "Recent studies demonstrate that UHRF1 is required for DNA methylation maintenance by targeting DNMT1 to DNA replication foci, presumably through its unique hemi-methylated DNA-binding activity and interaction with DNMT1.", "It is generally accepted that DNA methyltransferases carry out specific and non-overlapping functions, Dnmt3a and Dnmt3b being responsible for the establishment of methylation around the time of implantation and Dnmt1 ensuring that methylation is faithfully copied to daughter cells via what has come to be known as \"maintenance methylation.\"", "A new model is emerging that takes into account a contribution of the de novo enzymes Dnmt3a and Dnmt3b in the maintenance of the DNA methylation.", "We propose here observations in support of the hypothesis that the maintenance of methylation and subsequent silencing of a handful of germ line genes requires Dnmt3b but not Dnmt1.", "DNA methyltransferase 1 (Dnmt1) is the enzyme responsible for maintaining the methylation marks through cell division. However, the de novo methyltransferases, Dnmt3a and Dnmt3b, can also contribute to the maintenance of the methylation pattern.", "These new data support the notion that de novo DNMTs also have an important role in the maintenance of DNA methylation and suggest that, in addition to acting as oncogenes, they also behave as tumor suppressors.", "Structural insight into maintenance methylation by mouse DNA methyltransferase 1 (Dnmt1).", "The DNA methyltransferase Dnmt1 is responsible for the propagation of methylation patterns to the next generation via its preferential methylation of hemimethylated CpG sites in the genome; however, how Dnmt1 maintains methylation patterns is not fully understood.", "Usp7 and Uhrf1 control ubiquitination and stability of the maintenance DNA methyltransferase Dnmt1.", "In mammals Dnmt1 is the DNA methyltransferase chiefly responsible for maintaining genomic methylation patterns through DNA replication cycles, but how its maintenance activity is controlled is still not well understood.", "DMAP1 is a potent activator of DNMT1 methylation in vitro, suggesting that DMAP1 is a co-repressor that supports the maintenance and de novo action of DNMT1.", "A group of enzymes, the DNA methyltransferases (DNMTs) tightly regulate both the initiation and maintenance of these methyl marks.", "Maintenance of DNA methylation depends on DNA methyltransferase 1 (Dnmt1) and intracellular S-adenosylmethionine (SAM) levels, and is inhibited by S-adenosylhomocysteine (SAH).", "While DNMT3a is mostly involved in de novo methylation, DNMT1 acts as a maintenance methyltransferase.", "We propose a new model that suggests that the maintenance of DNA methylation relies not only on the recognition of hemimethylated DNA by DNA methyltransferase 1 (DNMT1) but also on the localization of the DNMT3A and DNMT3B enzymes to specific chromatin regions that contain methylated DNA.", "The maintenance methylase, DNMT1 (DNA methyltransferase 1), is a prominent enzyme in the process that is linked to DNA replication and drives the heritable nature of epigenetic modifications.", "We have shown previously that these drugs selectively and rapidly induce degradation of the maintenance DNA methyltransferase (DNMT) 1 by a proteasomal pathway.", "Inheritance of epigenetic information encoded by cytosine DNA methylation patterns is crucial for mammalian cell survival, in large part through the activity of the maintenance DNA methyltransferase (DNMT1).", "We and others have shown that DNA methyltransferase 1 (DNMT1), the maintenance methyltransferase, contributes to the cellular response to DNA damage, yet DNMT1's exact role in this process remains unclear.", "The maintenance function of Dnmt1 is regulated by its large regulatory N-terminal domain that interacts with other chromatin factors and is essential for the recognition of hemi-methylated DNA.", "In the absence of a human pituitary tumor cell line, small interfering RNA-mediated knockdown of the maintenance methyltransferase DNA methyltransferase (cytosine 5)-1 (Dnmt1) was used in the murine pituitary adenoma cell line AtT-20.", "We found that DNA methylation was maintained only when exogenous DNA methyltransferase 1 (DNMT1) and S-adenosyl methionine (SAM) were added to the reaction.", "We examined the expression of DNMT1 and DNMT3a, representative of a maintenance and de novo methyltransferase respectively, in response to in-vitro depolarization of cortical neurons, using standard techniques such as high potassium (KCl) or the sodium channel agonist veratridine.", "DNA methyltransferase-1 (DNMT1) has a higher specific activity on hemimethylated DNA than on unmethylated DNA, but this preference is too small to explain the faithful mitotic inheritance of genomic methylation patterns. New genetic studies in plants and mammals have identified a novel factor that increases the fidelity of maintenance methylation.", "Dnmt1 is the main maintenance methyltransferase in the mouse and its expression is regulated by a splicing mechanism that dictates the expression of stage-specific isoforms.", "Phosphorylation of serine-515 activates the Mammalian maintenance methyltransferase Dnmt1.", "DNA methyltransferase 1 methylates hemi-methylated CG sites generated during DNA replication.", "DNA methylation is catalyzed by a family of DNA methyltransferases (DNMTs) including the maintenance enzyme DNMT 1 and de novo methyltransferases DNMT 3a and DNMT 3b.", "Our data suggest that DNMT1 might be essential for maintenance of DNA methylation, proliferation, and survival of cancer cells.", "Maintenance DNA methyltransferase (Met1) and silencing of CpG-methylated foreign DNA in Volvox carteri.", "DNA methylation plays an important role in the gene-silencing network of higher eukaryotes. We have analyzed the 21.5-kb maintenance methyltransferase (M-MTase) gene, met1, of the multicellular green alga Volvox carteri.", "DNA damage-induced down-regulation of human Cdc25C and Cdc2 is mediated by cooperation between p53 and maintenance DNA (cytosine-5) methyltransferase 1.", "Methylation at the 5-position of DNA cytosine on the vertebrate genomes is accomplished by the combined catalytic actions of three DNA methyltransferases (DNMTs), the de novo enzymes DNMT3A and DNMT3B and the maintenance enzyme DNMT1.", "DNA methylation, the major form of epigenetic modifications, is catalyzed by the maintenance DNA methyltransferase (DNMT) 1 and/or the de novo methyltransferases DNMT3A and DNMT3B.", "The maintenance methylation of hemimethylated CpG sites by the DNA methyltransferase Dnmt1 is the molecular basis of the inheritance of DNA methylation patterns.", "The allosteric site(s) on Dnmt1 can regulate processes of de novo and maintenance DNA methylation in cells.", "Dnmt1 (DNA methyltransferase 1) is the principal enzyme responsible for maintenance of cytosine methylation at CpG dinucleotides in the mammalian genome.", "Maintenance of genomic methylation patterns is mediated primarily by DNA methyltransferase-1 (DNMT1).", "In this study, we showed that DNMT1, which encodes a methylation maintenance enzyme, is a transcriptional target of BRCA1.", "DNA methyltransferases (DNMTs) are essential for maintenance of aberrant methylation in cancer cells and play important roles in the development of cancers.", "DNA methyltransferase-1 (Dnmt1) is involved in the maintenance of DNA methylation patterns and is crucial for normal mammalian development.", "DNMT1, which is important for maintenance of methylation, increased across development and stayed high in adult cortex.", "Our results indicate that DNMT1 plays the main role in maintenance of methylation of CXCR4 promoter, while DNMT3B may function as an accessory DNA methyltransferase to modulate CXCR4 expression in AsPC1 cells.", "DNA methylation patterns are established and maintained by three DNA methyltransferases: DNMT1, DNMT3A, and DNMT3B.", "According to their structure and functions, DNA methyltransferases (Dnmts) are divided into two major families in mammalian cells: maintenance methyltransferase (Dnmt1) and de novo methyltransferases (Dnmt3a, Dnmt3b, and Dnmt3L).", "The 5-LOX DNA methylation increased with the age of the cells." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/21268065", "http://www.ncbi.nlm.nih.gov/pubmed/19468253", "http://www.ncbi.nlm.nih.gov/pubmed/7638194", "http://www.ncbi.nlm.nih.gov/pubmed/20506537", "http://www.ncbi.nlm.nih.gov/pubmed/18536530", "http://www.ncbi.nlm.nih.gov/pubmed/17312023", "http://www.ncbi.nlm.nih.gov/pubmed/22704242", "http://www.ncbi.nlm.nih.gov/pubmed/17929180", "http://www.ncbi.nlm.nih.gov/pubmed/19778587", "http://www.ncbi.nlm.nih.gov/pubmed/19282482", "http://www.ncbi.nlm.nih.gov/pubmed/22072770", "http://www.ncbi.nlm.nih.gov/pubmed/16963560", "http://www.ncbi.nlm.nih.gov/pubmed/22967183", "http://www.ncbi.nlm.nih.gov/pubmed/15799776", "http://www.ncbi.nlm.nih.gov/pubmed/22761581", "http://www.ncbi.nlm.nih.gov/pubmed/18665914", "http://www.ncbi.nlm.nih.gov/pubmed/22278882", "http://www.ncbi.nlm.nih.gov/pubmed/20940144", "http://www.ncbi.nlm.nih.gov/pubmed/21559294", "http://www.ncbi.nlm.nih.gov/pubmed/20864525", "http://www.ncbi.nlm.nih.gov/pubmed/19417133", "http://www.ncbi.nlm.nih.gov/pubmed/18302924", "http://www.ncbi.nlm.nih.gov/pubmed/20348135", "http://www.ncbi.nlm.nih.gov/pubmed/17989773", "http://www.ncbi.nlm.nih.gov/pubmed/20035856", "http://www.ncbi.nlm.nih.gov/pubmed/20007090", "http://www.ncbi.nlm.nih.gov/pubmed/22898819", "http://www.ncbi.nlm.nih.gov/pubmed/21553025", "http://www.ncbi.nlm.nih.gov/pubmed/17965600", "http://www.ncbi.nlm.nih.gov/pubmed/22563479", "http://www.ncbi.nlm.nih.gov/pubmed/22284370", "http://www.ncbi.nlm.nih.gov/pubmed/19825994", "http://www.ncbi.nlm.nih.gov/pubmed/19966177", "http://www.ncbi.nlm.nih.gov/pubmed/22934696", "http://www.ncbi.nlm.nih.gov/pubmed/18922972", "http://www.ncbi.nlm.nih.gov/pubmed/21625467", "http://www.ncbi.nlm.nih.gov/pubmed/23029374", "http://www.ncbi.nlm.nih.gov/pubmed/22633409", "http://www.ncbi.nlm.nih.gov/pubmed/20139415", "http://www.ncbi.nlm.nih.gov/pubmed/20364115", "http://www.ncbi.nlm.nih.gov/pubmed/16500889", "http://www.ncbi.nlm.nih.gov/pubmed/22413869", "http://www.ncbi.nlm.nih.gov/pubmed/20071334", "http://www.ncbi.nlm.nih.gov/pubmed/22323818", "http://www.ncbi.nlm.nih.gov/pubmed/22073356", "http://www.ncbi.nlm.nih.gov/pubmed/21389349", "http://www.ncbi.nlm.nih.gov/pubmed/22088914", "http://www.ncbi.nlm.nih.gov/pubmed/22064703", "http://www.ncbi.nlm.nih.gov/pubmed/21163962", "http://www.ncbi.nlm.nih.gov/pubmed/17033890", "http://www.ncbi.nlm.nih.gov/pubmed/21507353", "http://www.ncbi.nlm.nih.gov/pubmed/21913078", "http://www.ncbi.nlm.nih.gov/pubmed/16807237", "http://www.ncbi.nlm.nih.gov/pubmed/22538524", "http://www.ncbi.nlm.nih.gov/pubmed/21518897", "http://www.ncbi.nlm.nih.gov/pubmed/19932585", "http://www.ncbi.nlm.nih.gov/pubmed/18297739", "http://www.ncbi.nlm.nih.gov/pubmed/22048250", "http://www.ncbi.nlm.nih.gov/pubmed/23393137", "http://www.ncbi.nlm.nih.gov/pubmed/19016755", "http://www.ncbi.nlm.nih.gov/pubmed/21532572", "http://www.ncbi.nlm.nih.gov/pubmed/19819843", "http://www.ncbi.nlm.nih.gov/pubmed/20820192", "http://www.ncbi.nlm.nih.gov/pubmed/19173286", "http://www.ncbi.nlm.nih.gov/pubmed/19450230", "http://www.ncbi.nlm.nih.gov/pubmed/19789556", "http://www.ncbi.nlm.nih.gov/pubmed/17576694", "http://www.ncbi.nlm.nih.gov/pubmed/19923434" ]

[]

[ "http://www.uniprot.org/uniprot/CMT1_MAIZE", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0010216", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D019175", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0090116", "http://www.uniprot.org/uniprot/DCM_ECOLI", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D015257", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0003886" ]

[ "An altered TERalb is present in type 2 diabetic patients, both with normal and altered patterns of AER.\nTERalb is increased also in normo-albuminuric type 1 diabetic patients." ]

[ "yes" ]

[ "On the contrary, altered TERalb and increased carotid artery intimal thickness are shown by all hypertensive type 2 diabetic patients, both with normal and altered patterns of AER.", "Altered systemic capillary permeability characterizes insulin-resistant hypertensive patients with Metabolic Syndrome.", "TERalb is increased in normo-albuminuric type 1 diabetic patients. " ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/2060321", "http://www.ncbi.nlm.nih.gov/pubmed/21219847", "http://www.ncbi.nlm.nih.gov/pubmed/15616033", "http://www.ncbi.nlm.nih.gov/pubmed/2951101", "http://www.ncbi.nlm.nih.gov/pubmed/2949917", "http://www.ncbi.nlm.nih.gov/pubmed/3522326", "http://www.ncbi.nlm.nih.gov/pubmed/10922975", "http://www.ncbi.nlm.nih.gov/pubmed/18347777", "http://www.ncbi.nlm.nih.gov/pubmed/22950063", "http://www.ncbi.nlm.nih.gov/pubmed/10027580", "http://www.ncbi.nlm.nih.gov/pubmed/8187356", "http://www.ncbi.nlm.nih.gov/pubmed/7579054", "http://www.ncbi.nlm.nih.gov/pubmed/10703889", "http://www.ncbi.nlm.nih.gov/pubmed/3569694", "http://www.ncbi.nlm.nih.gov/pubmed/6642091", "http://www.ncbi.nlm.nih.gov/pubmed/2210073", "http://www.ncbi.nlm.nih.gov/pubmed/11395874", "http://www.ncbi.nlm.nih.gov/pubmed/8712223", "http://www.ncbi.nlm.nih.gov/pubmed/10405209", "http://www.ncbi.nlm.nih.gov/pubmed/2970919", "http://www.ncbi.nlm.nih.gov/pubmed/378740", "http://www.ncbi.nlm.nih.gov/pubmed/1547928", "http://www.ncbi.nlm.nih.gov/pubmed/9536925", "http://www.ncbi.nlm.nih.gov/pubmed/8960847", "http://www.ncbi.nlm.nih.gov/pubmed/22516624", "http://www.ncbi.nlm.nih.gov/pubmed/7698029", "http://www.ncbi.nlm.nih.gov/pubmed/1619500", "http://www.ncbi.nlm.nih.gov/pubmed/18712042", "http://www.ncbi.nlm.nih.gov/pubmed/8436254", "http://www.ncbi.nlm.nih.gov/pubmed/15581746", "http://www.ncbi.nlm.nih.gov/pubmed/15019550" ]

[]

[ "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=D012709", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D058065", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D000418", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D003920", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D003929" ]

[ "LDL receptor\"//\n\"ChREBP\"//\n\"ME\", \"malic enzyme\"//\n\"cytochrome P450 oxidoreductase\"//" ]

[ "LDL receptor", "ChREBP", "Carbohydrate response element binding protein", "ME", "malic enzyme", "cytochrome P450 oxidoreductase" ]

[ "our data suggests that TRbeta1-mediated down regulation of hepatic LDLr gene may play a critical role in iodine excess-induced hypercholesterolemic effects.", "These data suggest that ChREBP mRNA expression is positively regulated by TR-beta1 and TH at the transcriptional level in mammals. This novel observation indicates that TH fine-tunes hepatic lipogenesis via regulating SREBP-1c and ChREBP gene expression reciprocally.", "In contrast treatment with L-T3 produced an increase in S14 and ME but no change in TR beta-/- mice. From these results, it can be concluded that regulation of HR and EE are independent of TR beta. With the exception of serum cholesterol concentration and liver ME mRNA accumulation, all other markers of TH action examined during TH deprivation exhibited the expected responses in the absence of TR beta.", "However, the T3-activated expression of the GH gene in GH3-PV and ME gene in SK-Hep-1-PV was repressed by approximately 30% and 90%, respectively, indicating the lack of correlation of PV/TRpbeta1 protein ratio with the dominant negative potency of mutant PV.", "Transient cotransfection of P450R promoter/chloramphenicol acetyl transferase (CAT) constructs and the thyroid hormone receptor beta1 (TR beta1) expression plasmid into rat hepatoma H4IIE cells resulted in a 2.4-fold induction of promoter activity that was both T3 and TR beta1 dependent.", "At the molecular level, we detected a dose-dependent attenuation of hepatic low density lipoprotein receptor (LDLr) and thyroid hormone receptor beta1 (TRbeta1) expression in parallel to the change of serum cholesterol." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/19916081", "http://www.ncbi.nlm.nih.gov/pubmed/9224811", "http://www.ncbi.nlm.nih.gov/pubmed/9832432", "http://www.ncbi.nlm.nih.gov/pubmed/19324998", "http://www.ncbi.nlm.nih.gov/pubmed/10319950" ]

[]

[ "http://www.uniprot.org/uniprot/THBA_XENLA", "http://www.uniprot.org/uniprot/THB_SHEEP", "http://www.uniprot.org/uniprot/THB_PAROL", "http://www.uniprot.org/uniprot/THB_CHICK", "http://www.uniprot.org/uniprot/THBB_XENLA", "http://www.uniprot.org/uniprot/THB_DANRE", "http://www.uniprot.org/uniprot/THB_RAT", "http://www.uniprot.org/uniprot/THB_HUMAN", "http://www.uniprot.org/uniprot/THB_CAIMO", "http://www.uniprot.org/uniprot/THB_MOUSE", "http://www.uniprot.org/uniprot/THB_LITCT", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D037042" ]

[ "Yes. Numerous studies suggest that conserved noncoding elements span developmental regulatory genes and define regulatory domains." ]

[ "yes" ]

[ "Some characteristics of CNEs include their high frequency in mammalian genomes, their potential regulatory role in gene expression, and their enrichment in gene deserts nearby master developmental genes", "we review recent findings that disruptions of CNEs, within or at long distance from the coding sequences of key genes involved in NCC development, result in neurocristopathies via the alteration of tissue- or stage-specific long-distance regulation of gene expression", "Genomic regulatory blocks are chromosomal regions spanned by long clusters of highly conserved noncoding elements devoted to long-range regulation of developmental genes", "Analysis of CNEs, at least some of which are candidate regulatory elements, suggests that ancestral CNEs partitioned between gene duplicates. These results help explain the evolutionary pathways by which the developmentally important family of FgfD molecules arose and the deduced principles that guided FgfD evolution are likely applicable to the evolution of developmental regulation in many vertebrate multigene families", "Pan-vertebrate developmental cis-regulatory elements are discernible as highly conserved noncoding elements (HCNEs) and are often dispersed over large areas around the pleiotropic genes whose expression they control. On the loci of two developmental transcription factor genes, SOX3 and PAX6, we demonstrate that HCNEs conserved between human and zebrafish can be systematically and reliably tested for their regulatory function in multiple stable transgenes in zebrafish, and their genomic reach estimated with confidence using synteny conservation and HCNE density along these loci. HCNEs of both human and zebrafish function as specific developmental enhancers in zebrafish", "We show that human HCNEs result in expression patterns in zebrafish equivalent to those in mouse, establishing zebrafish as a suitable model for large-scale testing of human developmental enhancers", "HCNEs from the same area often drive overlapping patterns, suggesting that multiple regulatory inputs are required to achieve robust and precise complex expression patterns exhibited by developmental genes", "Organization of conserved elements near key developmental regulators in vertebrate genomes", "Further positional analysis of these conserved noncoding elements (CNEs) in the genome demonstrates that they cluster around genes involved in developmental regulation", "Ancora: a web resource for exploring highly conserved noncoding elements and their association with developmental regulatory genes", "Metazoan genomes contain arrays of highly conserved noncoding elements (HCNEs) that span developmental regulatory genes and define regulatory domains", "The most highly conserved noncoding elements (HCNEs) in mammalian genomes cluster within regions enriched for genes encoding developmentally important transcription factors (TFs). This suggests that HCNE-rich regions may contain key regulatory controls involved in development", "We found the largest mammal-teleost conserved chromosomal segments to be spanned by highly conserved noncoding elements (HCNEs), their developmental regulatory target genes, and phylogenetically and functionally unrelated \"bystander\" genes.", "Ancora: a web resource for exploring highly conserved noncoding elements and their association with developmental regulatory genes.", "Pan-vertebrate developmental cis-regulatory elements are discernible as highly conserved noncoding elements (HCNEs) and are often dispersed over large areas around the pleiotropic genes whose expression they control.", "Metazoan genomes contain arrays of highly conserved noncoding elements (HCNEs) that span developmental regulatory genes and define regulatory domains.", "Further positional analysis of these conserved noncoding elements (CNEs) in the genome demonstrates that they cluster around genes involved in developmental regulation.", "The most highly conserved noncoding elements (HCNEs) in mammalian genomes cluster within regions enriched for genes encoding developmentally important transcription factors (TFs).", "Disruption of long-distance highly conserved noncoding elements in neurocristopathies.", "Fish-mammal genomic comparisons have proved powerful in identifying conserved noncoding elements likely to be cis-regulatory in nature, and the majority of those tested in vivo have been shown to act as tissue-specific enhancers associated with genes involved in transcriptional regulation of development.", "Despite this, attempts at unearthing genome-wide regulatory elements conserved throughout the vertebrate lineage using BLAST-like approaches have thus far detected noncoding conservation in only a few hundred genes, mostly associated with regulation of transcription and development.", "Further positional analysis of these conserved noncoding elements (CNEs) in the genome demonstrates that they cluster around genes involved in developmental regulation.", "We found the largest mammal-teleost conserved chromosomal segments to be spanned by highly conserved noncoding elements (HCNEs), their developmental regulatory target genes, and phylogenetically and functionally unrelated \"bystander\" genes.", "Organization of conserved elements near key developmental regulators in vertebrate genomes.", "Pan-vertebrate developmental cis-regulatory elements are discernible as highly conserved noncoding elements (HCNEs) and are often dispersed over large areas around the pleiotropic genes whose expression they control" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/18282512", "http://www.ncbi.nlm.nih.gov/pubmed/16630819", "http://www.ncbi.nlm.nih.gov/pubmed/19562753", "http://www.ncbi.nlm.nih.gov/pubmed/21175683", "http://www.ncbi.nlm.nih.gov/pubmed/18279518", "http://www.ncbi.nlm.nih.gov/pubmed/16533910", "http://www.ncbi.nlm.nih.gov/pubmed/17387144", "http://www.ncbi.nlm.nih.gov/pubmed/19698106", "http://www.ncbi.nlm.nih.gov/pubmed/16859531", "http://www.ncbi.nlm.nih.gov/pubmed/19073165" ]

[]

[ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0051094", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0048589", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D050437", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0050793", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0032502" ]

[ "In children with heart failure evidence of the effect of enalapril is empirical. Enalapril was clinically safe and effective in 50% to 80% of for children with cardiac failure secondary to congenital heart malformations before and after cardiac surgery, impaired ventricular function , valvar regurgitation, congestive cardiomyopathy, , arterial hypertension, life-threatening arrhythmias coexisting with circulatory insufficiency. \nACE inhibitors have shown a transient beneficial effect on heart failure due to anticancer drugs and possibly a beneficial effect in muscular dystrophy-associated cardiomyopathy, which deserves further studies." ]

[ "50% to 80%" ]

[ "The responses to IV KCl were attenuated by concomitant furosemide (p = 0.01), amphotericin B (p < 0.01), and KCl in parenteral nutrition (p < 0.01). The responses were augmented by concomitant enalapril", "To determine whether an angiotensin-converting enzyme (ACE) inhibitor, enalapril, prevents cardiac function deterioration (defined using maximal cardiac index [MCI] on exercise testing or increase in left ventricular end-systolic wall stress [LVESWS]) in long-term survivors of pediatric cancer.", "Enalapril treatment did not influence exercise performance, but did reduce LVESWS in the first year", "Patients with intraatrial baffle procedure for transposition of the great arteries (TGA) have diastolic dysfunction, decreased exercise capacity, stroke volume response and elevated systemic vascular resistance (SVR) during exercise.", "We conclude that short-term (<1 year) use of enalapril does not improve exercise performance in patients with TGA in whom the intraatrial baffle procedure has been performed.", "A common late effect of doxorubicin therapy for childhood cancer is reduced left-ventricular (LV) wall thickness resulting in elevated LV afterload and depressed LV function. Many children are given angiotensin-converting enzyme inhibitors, which have been studied primarily in adults. We document the long-term effects of angiotensin-converting enzyme inhibitors in doxorubicin-treated survivors of childhood cancer.", "In doxorubicin-treated long-term survivors of childhood cancer, enalapril-induced improvement in LV structure and function is transient. The primary defect, which is LV wall thinning, continues to deteriorate, and thus the short-term improvement was mostly related to lowered diastolic blood pressure.", "Patients who have undergone the Fontan procedure have decreased cardiac output, increased systemic vascular resistance, abnormal diastolic function, and decreased exercise capacity compared with normal people.", "We conclude that enalapril administration for 10 weeks does not alter abnormal systemic vascular resistance, resting cardiac index, diastolic function, or exercise capacity in patients who have undergone a Fontan procedure.", "Angiotensin convertase inhibitor (Enalapril) was used in 51 children aged 4 days up to 18 years (mean 4.3 +/- 5.5, years). As many as 27 subjects were newborns (4) and infants (23). The patients suffered from circulatory insufficiency due to congestive cardiomyopathy (13 cases). 6 treated subjects suffered from circulatory insufficiency due to congenital heart malformations before cardiac surgery and 22 after it (including complex malformations operated according to Fontan method). 10 children were treated because of arterial hypertension. 4 subjects suffered form life-threatening arrhythmias coexisting with circulatory insufficiency.", "4 patients (8%) died during treatment but their deaths can not be related to angiotensin convertase inhibitor therapy. In the other children (82%) the beneficial influence of angiotensin convertase inhibitor use was found (improvement in comparison with the state before convertase inhibitor introduction). In 10% of subjects enalapril did not show any significant therapeutic effect", "We conclude that the combination of ACE inhibitor and beta-blocker deserves further exploration for inclusion in any management regimen for the treatment of muscular dystrophy-associated cardiomyopathy.", "Addition of these medications, never before attempted in the management of cardiomyopathy associated with generalized myopathic disease, complemented each other in relieving symptoms and reversing signs of congestive heart failure and DCM.", "Enalapril was clinically safe and effective for children with cardiac failure secondary to ventricular impairment, valvar regurgitation, or after cardiac surgery. Renal failure was a problem in young infants with left-to-right shunts.", "In a tertiary referral centre 63 patients underwent 67 treatment periods with enalapril. The median age was 5.4 months. All children had signs of heart failure: congestive cardiac failure with breathlessness at rest was present in 88%. Haemodynamic groups were left-to-right shunt (n = 15), impaired ventricular function (n = 14), after cardiac surgery (n = 23), valvar regurgitation (n = 12), and hypertension (n = 3). Serial clinical, radiological, and laboratory data were used to judge outcome. The mean (SD) maximal dose was 0.30 (0.21) mg/kg/day. Thirty nine (58%) patients improved, 20 (30%) showed no improvement, and eight (12%) had side effects requiring discontinuation of enalapril.", "We studied the inhibition of angiotensin converting enzyme (ACE) in eight infants with congestive heart failure (CHF) poorly controlled with digoxin and diuretics, treated orally with 0.25 mg kg-1 enalapril maleate once a day", "In infants with CHF, mean baseline ACE activity was significantly higher than in control infants", "Converting enzyme inhibitors may benefit \"heart failure\" associated with large ventricular septal defects and normal or mildly elevated pulmonary resistance." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/1318542", "http://www.ncbi.nlm.nih.gov/pubmed/23124387", "http://www.ncbi.nlm.nih.gov/pubmed/8110005", "http://www.ncbi.nlm.nih.gov/pubmed/12530495", "http://www.ncbi.nlm.nih.gov/pubmed/9315539", "http://www.ncbi.nlm.nih.gov/pubmed/7576410", "http://www.ncbi.nlm.nih.gov/pubmed/8512763", "http://www.ncbi.nlm.nih.gov/pubmed/14990637", "http://www.ncbi.nlm.nih.gov/pubmed/9381720", "http://www.ncbi.nlm.nih.gov/pubmed/12454107" ]

[]

[ "http://www.biosemantics.org/jochem#4176194", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D006333", "http://www.disease-ontology.org/api/metadata/DOID:6000", "http://www.biosemantics.org/jochem#4249241", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D054144", "http://www.biosemantics.org/jochem#4175579", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D054143", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004656", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D015773", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D002648", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D006321", "http://www.disease-ontology.org/api/metadata/DOID:9775", "http://www.biosemantics.org/jochem#4250224", "http://www.disease-ontology.org/api/metadata/DOID:9651" ]

[ "Myasthenia gravis (MG) is a neuromuscular disease which has been associated with an increased risk of glucocorticoid-induced osteoporosis. Thymectomy can also increase risk for osteoporosis. Appropriate osteoporosis preventive measures can reduce osteoporosis risk in MG patients." ]

[ "yes" ]

[ "We performed PVP in 4 patients with generalized MG associated with recent steroid-induced symptomatic VFs. ", "In this case report, we used tacrolimus to successfully treat a 13-year-old boy with ocular MG who had suffered from severe steroid complications, including a failure of thrive and osteoporosis.", " INTRODUCTION: Myasthenia gravis (MG) is a neuromuscular disease which has been associated with an increased falls risk and glucocorticoid-induced osteoporosis, recognized determinants of increased fracture risk. ", "RESULTS: Compared to the control cohort, there was no statistically significant increased risk observed in patients with MG for any fracture (adjusted hazard ratio [AHR] 1.11; 95 % confidence interval [CI], 0.84-1.47) or osteoporotic fractures (AHR 0.98 [95 % CI 0.67-1.41]). Further, use of oral glucocorticoids up to a cumulative dose exceeding 5 g prednisolone equivalents did not increase risk of osteoporotic fracture (AHR 0.99 [95 % CI, 0.31-3.14]) compared with MG patients without glucocorticoid exposure.", "The RANKL/OPG ratio and indices of bone metabolisms are also not affected by THX, although THX increases the levels of IL-7 and RANKL.", "Both disorders had been controlled for around 15 years by oral prednisolone and a cholinesterase inhibitor following surgical removal of invasive thymoma and radiotherapy, but muscular weakness due to myalgia and an increase in serum levels of myogenic enzymes, mainly ascribable to the recurrence of PM, reappeared immediately after cessation of these drugs, which was done because the patient had multiple bone fractures and severe osteoporosis due to the long-term corticosteroid therapy. ", "We measured bone density in 36 patients (26 females and 10 males) who had undergone long-term prednisolone administration, and found a decrease in bone density in 31% of female patients and osteoporosis in only 11.5% (three cases).", "In conclusion, prednisolone-treated patients with myasthenia gravis have an acceptable risk of bone loss if prophylactic medication is administered.", "INTRODUCTION: Myasthenia gravis (MG) is a neuromuscular disease which has been associated with an increased falls risk and glucocorticoid-induced osteoporosis, recognized determinants of increased fracture risk.", "Alendronate should be used with caution in patients with myasthenia gravis who have corticosteroid-induced osteoporosis", "In this paper we present two cases of young women who developed severe PAO with vertebral fractures: a 42-year-old woman with a family history of osteoporosis, and a 21-year-old woman affected with myasthenia gravis", "Myasthenia gravis (MG) is a neuromuscular disease which has been associated with an increased falls risk and glucocorticoid-induced osteoporosis, recognized determinants of increased fracture risk" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/15168159", "http://www.ncbi.nlm.nih.gov/pubmed/25122205", "http://www.ncbi.nlm.nih.gov/pubmed/25285145", "http://www.ncbi.nlm.nih.gov/pubmed/22531999", "http://www.ncbi.nlm.nih.gov/pubmed/16690366", "http://www.ncbi.nlm.nih.gov/pubmed/22840813", "http://www.ncbi.nlm.nih.gov/pubmed/15003307", "http://www.ncbi.nlm.nih.gov/pubmed/11328209", "http://www.ncbi.nlm.nih.gov/pubmed/24935165", "http://www.ncbi.nlm.nih.gov/pubmed/2237235", "http://www.ncbi.nlm.nih.gov/pubmed/23543381" ]

[]

[ "http://www.disease-ontology.org/api/metadata/DOID:437", "http://www.disease-ontology.org/api/metadata/DOID:11476" ]

[ "Chromogranin A is a marker for neuroendocrine cells" ]

[ "neuroendocrine cells" ]

[ "Neuroendocrine differentiation (chromogranin A and/or synaptophysin positivity) ", "All paragangliomas were universally positive for chromogranin A ", "chromogranin A (CGA) is a useful marker for pancreatic neuroendocrine tumors (pNET)", "Together with Chromogranin B and Secretogranins, Chromogranin A (CGA) is stored in secretory (chromaffin) granules of the diffuse neuroendocrine system", "Chromogranin A (CgA) is the most important general tumour marker used in the diagnosis and follow-up of patients with neuroendocrine tumours (NET).", "Chromogranin A (CgA) not only plays an important role in pathologic diagnosis, but is also used as a circulating biomarker in patients with gastroenteropancreatic neuroendocrine neoplasm (GEP-NEN).", "numbers of chromogranin A (CHGA)-positive enteroendocrine cells (EEC", " CgA is a reliable serum diagnostic biomarker for PNETs", "Chromogranin A (CgA) was considered as the most practical and useful serum tumor marker in PNET patients.", "the neuroendocrine markers chromogranin A and synaptophysin;" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/25532001", "http://www.ncbi.nlm.nih.gov/pubmed/25294372", "http://www.ncbi.nlm.nih.gov/pubmed/25294889", "http://www.ncbi.nlm.nih.gov/pubmed/25394660", "http://www.ncbi.nlm.nih.gov/pubmed/24888775", "http://www.ncbi.nlm.nih.gov/pubmed/24897131", "http://www.ncbi.nlm.nih.gov/pubmed/25177680", "http://www.ncbi.nlm.nih.gov/pubmed/25099181", "http://www.ncbi.nlm.nih.gov/pubmed/25220535", "http://www.ncbi.nlm.nih.gov/pubmed/25501094" ]

[ { "p": "http://purl.uniprot.org/core/reviewed", "s": "http://purl.uniprot.org/uniprot/P33716", "o": "true" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_503333373136007", "o": "Chromogranin-A" }, { "p": "http://purl.uniprot.org/core/recommendedName", "s": "http://purl.uniprot.org/uniprot/P33716", "o": "http://linkedlifedata.com/resource/#_503333373136007" }, { "p": "http://purl.uniprot.org/core/classifiedWith", "s": "http://purl.uniprot.org/uniprot/P33716", "o": "http://purl.uniprot.org/keywords/964" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://purl.uniprot.org/keywords/964", "o": "Secreted" } ]

[ "http://www.uniprot.org/uniprot/CMGA_BOVIN", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D000943", "http://www.biosemantics.org/jochem#4266983", "http://www.biosemantics.org/jochem#4262122", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D053379", "http://www.biosemantics.org/jochem#4218257", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D002864", "http://www.uniprot.org/uniprot/CMGA_HUMAN" ]

[ "Selective sweep is a phenomenon in which the fixation of strongly beneficial alleles within a population reduces genetic diversity at partially linked neutral loci. Reduced variation or deviations from neutrality, along with an excess of fixed replacement sites, are indicative of selective sweep." ]

[ "no" ]

[ "An East African population that gave rise to non-Africans underwent a selective sweep affecting the subcentromeric region where MTMR8 is located. This and similar sweeps in four other regions of the X chromosome, documented in the literature, effectively reduced genetic diversity of non-African chromosomes", "a selective sweep that has removed genetic variation from much of the drive X chromosome.", "evidence of reduced diversity and an excess of fixed replacement sites, consistent with a species-wide selective sweep.", "recent independent selective sweeps in AGO2 have reduced genetic variation", "episodes of natural selection (likely a selective sweep) predating the coalescent of human lineages, within the last 25 million years, account for the observed reduced diversity", "reduced variation or deviations from neutrality that might indicate a recent selective sweep", "Consider a genetic locus carrying a strongly beneficial allele which has recently fixed in a large population. As strongly beneficial alleles fix quickly, sequence diversity at partially linked neutral loci is reduced. This phenomenon is known as a selective sweep.", "a local selective sweep or demographic process that reduced variability", "reduced variation (a selective sweep)", "the mtDNA diversity, but not the nuclear DNA diversity, has been reduced relative to the neutral expectation of molecular evolution, suggesting the action of a selective sweep", "Furthermore, the amount of genetic variation after a selective sweep is expected to be unequal over demes: a greater reduction in expected heterozygosity occurs in the subpopulation from which the beneficial mutation originates than in its neighboring subpopulations.", "Our observation of reduction in variation at both intragenic and flanking loci of mutant pfcrt gene confirmed the selective sweep model of natural selection in chloroquine resistant P.", "A selective sweep describes the reduction of linked genetic variation due to strong positive selection.", "In these situations, adaptation should commonly produce 'soft' selective sweeps, where multiple adaptive alleles sweep through the population at the same time, either because the alleles were already present as standing genetic variation or arose independently by recurrent de novo mutations.", "CONCLUSIONS: The severe reduction in nucleotide variation at OsAMT1;1 in rice was caused by a selective sweep around OsAMT1;1, which may reflect the nitrogen uptake system under strong selection by the paddy soil during the domestication of rice.", "A selective sweep describes the reduction of linked genetic variation due to strong positive selection" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/17396267", "http://www.ncbi.nlm.nih.gov/pubmed/21624997", "http://www.ncbi.nlm.nih.gov/pubmed/21076829", "http://www.ncbi.nlm.nih.gov/pubmed/16951057", "http://www.ncbi.nlm.nih.gov/pubmed/20352120", "http://www.ncbi.nlm.nih.gov/pubmed/22087274", "http://www.ncbi.nlm.nih.gov/pubmed/24075201", "http://www.ncbi.nlm.nih.gov/pubmed/16322515", "http://www.ncbi.nlm.nih.gov/pubmed/24465214", "http://www.ncbi.nlm.nih.gov/pubmed/24126360", "http://www.ncbi.nlm.nih.gov/pubmed/21705748", "http://www.ncbi.nlm.nih.gov/pubmed/20140188", "http://www.ncbi.nlm.nih.gov/pubmed/24282552", "http://www.ncbi.nlm.nih.gov/pubmed/22491190", "http://www.ncbi.nlm.nih.gov/pubmed/21385389", "http://www.ncbi.nlm.nih.gov/pubmed/20978039", "http://www.ncbi.nlm.nih.gov/pubmed/18346126", "http://www.ncbi.nlm.nih.gov/pubmed/16339379", "http://www.ncbi.nlm.nih.gov/pubmed/16367838" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012641", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D014644" ]

[ "X-linked Charcot-Marie-Tooth disease type 5 (CMTX5), Arts syndrome, and non-syndromic sensorineural deafness (DFN2) are allelic syndromes, caused by reduced activity of phosphoribosylpyrophosphate synthetase 1 (PRS-I) due to loss-of-function mutations in PRPS1." ]

[ "X-linked Charcot-Marie-Tooth disease type 5 (CMTX5)", "Arts syndrome", "Non-syndromic sensorineural deafness (DFN2)" ]

[ "X-linked Charcot-Marie-Tooth disease, Arts syndrome, and prelingual non-syndromic deafness form a disease continuum: evidence from a family with a novel PRPS1 mutation", "X-linked Charcot-Marie-Tooth disease type 5 (CMTX5), Arts syndrome, and non-syndromic sensorineural deafness (DFN2) are allelic syndromes, caused by reduced activity of phosphoribosylpyrophosphate synthetase 1 (PRS-I) due to loss-of-function mutations in PRPS1", "Our findings demonstrate that CMTX5, Arts syndrome and DFN2 are phenotypic clusters on an intrafamilial continuum, including overlapping phenotypes even within individuals. The respective phenotypic presentation seems to be determined by the exact PRPS1 mutation and the residual enzyme activity, the latter being largely influenced by the degree of skewed X-inactivation", "Mutations in PRPS1 are associated with a spectrum of non-syndromic to syndromic hearing loss", "Gain of function mutations in PRPS1 cause a superactivity of the PRS-I protein whereas the loss-of-function mutations result in X-linked nonsyndromic sensorineural deafness type 2 (DFN2), or in syndromic deafness including Arts syndrome and X-linked Charcot-Marie-Tooth disease-5 (CMTX5)", "X-linked Charcot-Marie-Tooth disease, Arts syndrome, and prelingual non-syndromic deafness form a disease continuum: evidence from a family with a novel PRPS1 mutation.", "Mutations described thus far in PRPS1 are all missense mutations that result in PRS-I superactivity or in variable levels of decreased activity, resulting in X-linked Charcot-Marie-Tooth disease-5 (CMTX5), Arts syndrome, and X-linked nonsyndromic sensorineural deafness (DFN2).", "Mutations described thus far in PRPS1 are all missense mutations that result in PRS-I superactivity or in variable levels of decreased activity, resulting in X-linked Charcot-Marie-Tooth disease-5 (CMTX5), Arts syndrome, and X-linked nonsyndromic sensorineural deafness (DFN2)", "X-linked Charcot-Marie-Tooth disease type 5 (CMTX5), Arts syndrome, and non-syndromic sensorineural deafness (DFN2) are allelic syndromes, caused by reduced activity of phosphoribosylpyrophosphate synthetase 1 (PRS-I) due to loss-of-function mutations in PRPS1", "X-linked Charcot-Marie-Tooth disease type 5 (CMTX5) is caused by mutations in the gene encoding phosphoribosyl pyrophosphate synthetase I (PRPS1)", "Gain of function mutations in PRPS1 cause a superactivity of the PRS-I protein whereas the loss-of-function mutations result in X-linked nonsyndromic sensorineural deafness type 2 (DFN2), or in syndromic deafness including Arts syndrome and X-linked Charcot-Marie-Tooth disease-5 (CMTX5).", "The spectrum of PRPS1-related disorders associated with reduced activity includes Arts syndrome, Charcot-Marie-Tooth disease-5 (CMTX5) and X-linked non-syndromic sensorineural deafness (DFN2).", "X-linked Charcot-Marie-Tooth disease, Arts syndrome, and prelingual non-syndromic deafness form a disease continuum: evidence from a family with a novel PRPS1 mutation." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/24528855", "http://www.ncbi.nlm.nih.gov/pubmed/23190330", "http://www.ncbi.nlm.nih.gov/pubmed/20380929", "http://www.ncbi.nlm.nih.gov/pubmed/24961627", "http://www.ncbi.nlm.nih.gov/pubmed/24285972" ]

[]

[]

[ "antioxidant supplementation \nHowever there are no clear evidencies on the clinical and prognostic benefit of this supplementation. \nCurrently there areno recommendation for the antioxidant therapy in patients with coronary artery disease.\nCurrently the American Heart Association recommends consumption of a balanced diet with emphasis on antioxidant-rich fruits and vegetables but does not recommend antioxidant supplementation for the general population." ]

[ "no" ]

[ "We and others have published observational epidemiologic studies in support of vitamins in the primary prevention of CVD, but the results from intervention studies are mixed.", "For vitamin E, observational data suggest benefit at doses of 100 to 400 IU/d. Results from recent large-scale trials are mixed, with some showing modest benefit but others suggesting no benefit, especially for secondary prevention. Results for B vitamins are also mixed and further complicated by the recent folate fortification of the flour supply. If greater B vitamin intake does reduce CVD, the benefits are likely to be greatest for primary prevention and in populations with intake below dietary reference standards. ", "In the dose-response meta-analysis, each 30 mg/day increase in vitamin C, 30 IU/day increase in vitamin E, and 1 mg/day increase in beta-carotene yielded the estimated overall relative risk for CHD of 1.01 (95% CI, 0.99-1.02), 0.96 (95% CI, 0.94-0.99), and 1.00 (95% CI, 0.88-1.14), respectively. CONCLUSIONS: Our findings in this meta-analysis suggest that an increase in dietary intake of antioxidant vitamins has encouraging prospects for possible CHD prevention.", "High levels of α-tocopherol in serum were associated with 30% lower CAD risk in another study (HR 0.71; 95%CI 0.53-0.94). Among minerals (zinc, selenium, and chromium), an inverse association between zinc and CAD was observed; levels lower than 14.1 µmol/L were associated with an increased risk for CAD (RR 1.70; 95%CI 1.21-2.38).", "The information available on this issue is scarce. Further prospective studies are needed to elucidate the role of these nutrients in the cardiovascular risk of patients with diabetes.", "Coenzyme Q10 supplementation at a dosage of 150 mg appears to decrease the inflammatory marker IL-6 in patients with CAD.", " Coenzyme Q10 supplements at a dose of 150 mg can decrease oxidative stress and increase antioxidant enzyme activity in patients with CAD. A higher dose of coenzyme Q10 supplements (>150 mg/d) might promote rapid and sustainable antioxidation in patients with CAD.", "Alpha-tocopherol or beta-carotene supplementation has no protective effect on macrovascular outcomes or total mortality of diabetic male smokers.", "Sodium selenite supplementation increases GPx-1 activity in endothelial cells and in CAD patients. Future studies have to demonstrate whether long-term CAD outcome can be improved.", "After 7.3 years of treatment and follow-up, a combination pill of folic acid, vitamin B6, and vitamin B12 did not reduce a combined end point of total cardiovascular events among high-risk women, despite significant homocysteine lowering.", " In this population-based study, vitamin E use was unrelated to mortality, but this apparently null finding seems to represent a combination of increased mortality in those with severe cardiovascular disease and a possible protective effect in those without.", " In this large cohort of apparently healthy US male physicians, self-selected supplementation with vitamin E, vitamin C, or multivitamins was not associated with a significant decrease in total CVD or CHD mortality. ", "The American Heart Association has recommended consumption of a balanced diet with emphasis on antioxidant-rich fruits and vegetables but has made no recommendations regarding vitamin E supplementation for the general population. Although vitamin E supplementation seems to be safe for most people, recommendations from health care professionals should reflect the uncertainty of established benefit as demonstrated in clinical trials", "Recent studies show that supplementation with antioxidant vitamins E and C have benefits in CHD prevention; however, supplementation with beta-carotene may have deleterious effects and is not recommended. Current evidence suggests that patients with CHD would probably benefit from taking vitamin E in a dosage of 400 IU per day and vitamin C in a dosage of 500 to 1,000 mg per day. Clinicians may also want to consider vitamin supplementation for CHD prevention in high-risk patients. Folate lowers elevated homocysteine levels, but evidence for routine supplemental use does not yet exist. ", "In patients at high risk for cardiovascular events, treatment with vitamin E for a mean of 4.5 years had no apparent effect on cardiovascular outcomes." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/19774218", "http://www.ncbi.nlm.nih.gov/pubmed/10575394", "http://www.ncbi.nlm.nih.gov/pubmed/8164066", "http://www.ncbi.nlm.nih.gov/pubmed/8650957", "http://www.ncbi.nlm.nih.gov/pubmed/23877741", "http://www.ncbi.nlm.nih.gov/pubmed/11944023", "http://www.ncbi.nlm.nih.gov/pubmed/9430400", "http://www.ncbi.nlm.nih.gov/pubmed/20400494", "http://www.ncbi.nlm.nih.gov/pubmed/18377792", "http://www.ncbi.nlm.nih.gov/pubmed/9877124", "http://www.ncbi.nlm.nih.gov/pubmed/18277182", "http://www.ncbi.nlm.nih.gov/pubmed/12968298", "http://www.ncbi.nlm.nih.gov/pubmed/10987596", "http://www.ncbi.nlm.nih.gov/pubmed/9193380", "http://www.ncbi.nlm.nih.gov/pubmed/9746269", "http://www.ncbi.nlm.nih.gov/pubmed/9723625", "http://www.ncbi.nlm.nih.gov/pubmed/9849356", "http://www.ncbi.nlm.nih.gov/pubmed/19033020", "http://www.ncbi.nlm.nih.gov/pubmed/22645453", "http://www.ncbi.nlm.nih.gov/pubmed/22293859", "http://www.ncbi.nlm.nih.gov/pubmed/15531665", "http://www.ncbi.nlm.nih.gov/pubmed/8479464", "http://www.ncbi.nlm.nih.gov/pubmed/18548846", "http://www.ncbi.nlm.nih.gov/pubmed/15567903", "http://www.ncbi.nlm.nih.gov/pubmed/12675072", "http://www.ncbi.nlm.nih.gov/pubmed/15302616", "http://www.ncbi.nlm.nih.gov/pubmed/8602181", "http://www.ncbi.nlm.nih.gov/pubmed/11192356", "http://www.ncbi.nlm.nih.gov/pubmed/9659191", "http://www.ncbi.nlm.nih.gov/pubmed/10386507", "http://www.ncbi.nlm.nih.gov/pubmed/7977015", "http://www.ncbi.nlm.nih.gov/pubmed/8479463", "http://www.ncbi.nlm.nih.gov/pubmed/12204790", "http://www.ncbi.nlm.nih.gov/pubmed/12069675", "http://www.ncbi.nlm.nih.gov/pubmed/23335472", "http://www.ncbi.nlm.nih.gov/pubmed/10077397", "http://www.ncbi.nlm.nih.gov/pubmed/16603825", "http://www.ncbi.nlm.nih.gov/pubmed/8946266", "http://www.ncbi.nlm.nih.gov/pubmed/10711786", "http://www.ncbi.nlm.nih.gov/pubmed/15153272", "http://www.ncbi.nlm.nih.gov/pubmed/11089430", "http://www.ncbi.nlm.nih.gov/pubmed/12741415", "http://www.ncbi.nlm.nih.gov/pubmed/7695869", "http://www.ncbi.nlm.nih.gov/pubmed/12732794", "http://www.ncbi.nlm.nih.gov/pubmed/22254063", "http://www.ncbi.nlm.nih.gov/pubmed/10329064", "http://www.ncbi.nlm.nih.gov/pubmed/20350251", "http://www.ncbi.nlm.nih.gov/pubmed/10656300", "http://www.ncbi.nlm.nih.gov/pubmed/9164706", "http://www.ncbi.nlm.nih.gov/pubmed/19859067", "http://www.ncbi.nlm.nih.gov/pubmed/24489984", "http://www.ncbi.nlm.nih.gov/pubmed/21115589", "http://www.ncbi.nlm.nih.gov/pubmed/15117174", "http://www.ncbi.nlm.nih.gov/pubmed/10812586", "http://www.ncbi.nlm.nih.gov/pubmed/23055813", "http://www.ncbi.nlm.nih.gov/pubmed/10639540", "http://www.ncbi.nlm.nih.gov/pubmed/15585762", "http://www.ncbi.nlm.nih.gov/pubmed/17275460", "http://www.ncbi.nlm.nih.gov/pubmed/15693087", "http://www.ncbi.nlm.nih.gov/pubmed/23833580", "http://www.ncbi.nlm.nih.gov/pubmed/21996047", "http://www.ncbi.nlm.nih.gov/pubmed/12492632", "http://www.ncbi.nlm.nih.gov/pubmed/18460663", "http://www.ncbi.nlm.nih.gov/pubmed/10498115", "http://www.ncbi.nlm.nih.gov/pubmed/8570438", "http://www.ncbi.nlm.nih.gov/pubmed/10696633", "http://www.ncbi.nlm.nih.gov/pubmed/12090883", "http://www.ncbi.nlm.nih.gov/pubmed/8472392", "http://www.ncbi.nlm.nih.gov/pubmed/11702901", "http://www.ncbi.nlm.nih.gov/pubmed/23022248", "http://www.ncbi.nlm.nih.gov/pubmed/10600089", "http://www.ncbi.nlm.nih.gov/pubmed/22342390" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D000975", "http://www.disease-ontology.org/api/metadata/DOID:3393", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D023921", "http://www.disease-ontology.org/api/metadata/DOID:4248", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D003324", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D003327", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D010361", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D054059", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D019587" ]

[ "HuR is an RNA-binding protein that can stabilize labile mRNAs containing AU-rich elements in their 3' untranslated regions and has been shown to shuttle between the nucleus and cytoplasm. HuR function was previously shown to be implicated in the maintenance of a \"young cell\" phenotype in models of replicative cellular senescence. Loss of HuR is linked to reduced expression of proliferative genes during replicative senescence. Importantly, overexpression of HuR in senescent cells restored a \"younger\" phenotype, while a reduction in HuR expression accentuated the senescent phenotype. HuR associated with the 3' untranslated region of the mRNA encoding the longevity and stress-response protein SIRT1, stabilized the SIRT1 mRNA, and increased SIRT1 expression levels. In mesenchymal cells HuR plays a dominant role in lung development and as a key post-transcriptional regulator of networks guiding tissue remodeling during branching morphogenesis. In fibroblasts knockdown of HuR decreased the endogenous expression of TGFβ1 under exogenous TGFβ1 treatment, simultaneously with the decrease of Col1a, Col3a and fibronectin expression. HuR (human antigen R), represses ARF mRNA translation, thereby maintaining the replicative life span of mouse embryonic fibroblasts (MEFs). HuR is considered a global regulator of cell-cycle progression and tumorigenesis. Through its post-transcriptional influence on specific target mRNAs, HuR can alter the cellular response to proliferative, stress, apoptotic, differentiation, senescence, inflammatory and immune stimuli." ]

[]

[ "The H(2)O(2)-dependent sGCβ1 upregulation was attributable to sGCβ1 mRNA stabilization, conditioned by the translocation of the mRNA-binding protein HuR from the nucleus to the cytosol, and the increased mRNA binding of HuR to the sGCβ1 3' untranslated region.", "HuR silencing reversed the effects of H(2)O(2) on sGCβ1 levels and cGMP synthesis.", "Our results identify H(2)O(2) as an endogenous mediator contributing to the regulation of vascular tone and point to a key role of HuR in sGCβ1 mRNA stabilization.", "Cytoplasmic export of the RNA-binding protein HuR, a process that critically regulates its function, was recently shown to be inhibited by the AMP-activated protein kinase (AMPK)", "HuR function was previously shown to be implicated in the maintenance of a \"young cell\" phenotype in models of replicative cellular senescence.", "The in vitro binding selectivity of HuR is indicative of an ARE sequence's ability to destabilize a mRNA in vivo, suggesting a critical role for HuR in the regulation of mRNA degradation.", "urification and subsequent analyses demonstrate that this 32 kDa protein is identical to a recently identified member of the Elav-like gene family (ELG) called HuR.", "We also show that HuR can be induced to redistribute from the nucleus to the cytoplasm and that this redistribution is associated with an altered function.", "RNA stabilization by the AU-rich element binding protein, HuR, an ELAV protein.", "ELAV protein HuA (HuR) can redistribute between nucleus and cytoplasm and is upregulated during serum stimulation and T cell activation.", " HuR is an RNA-binding protein that can stabilize labile mRNAs containing AU-rich elements in their 3' untranslated regions and has been shown to shuttle between the nucleus and cytoplasm (18, 19).", "We propose that HuR first may bind AU-rich element-containing mRNAs in the nucleus and then escort them through the nuclear pore, providing protection during and after export to the cytoplasmic compartment.", "Taken together, these data show that a correlation exists between the binding of HuR to the AU-rich motif in vitro and the destabilizing properties conferred by this sequence in vivo.", "HuR interacts with AU-rich elements in the 3'UTR of many protooncogenes, cytokines, and transcription factors, thereby regulating the expression of these mRNAs on the posttranscriptional level.", "Transfection assays with a CAT reporter construct revealed reduced expression of the reporter, suggesting that HuR may be involved in the fine-tuning of the expression of the NF1 gene.", "Importantly, overexpression of HuR in senescent cells restored a \"younger\" phenotype, while a reduction in HuR expression accentuated the senescent phenotype.", "Our studies highlight a critical role for HuR during the process of replicative senescence.", "Here, using two models of replicative senescence, we describe the influence of the RNA-binding protein HuR in regulating the expression of several genes whose expression decreases during senescence", "We demonstrate that HuR levels, HuR binding to target mRNAs encoding proliferative genes, and the half-lives of such mRNAs are lower in senescent cells.", "Loss of HuR is linked to reduced expression of proliferative genes during replicative senescence.", "Although in vitro experiments showed indiscriminate binding of Hu proteins synthesized in bacterial systems to many different AU-rich elements (AREs), in vivo studies have pointed to a cytoplasmic role for HuR protein in antagonizing the rapid decay of some specific ARE-containing mRNAs, depending on physiological situations.", "Our data suggest that the ARE-binding specificity of HuR in vivo is modulated to interact only with and thus regulate specific AREs in a cell type- and physiological state-dependent manner.", "Overexpression of HuD and HuR in murine fibroblasts caused a striking stabilization of the endogenous MARCKS mRNA even under conditions when the MARCKS mRNA is normally actively degraded, i.e. after treating cells with phorbol ester. ", "Our findings implicate mRNA stabilization in the cytokine-mediated increase in eotaxin expression and strongly suggest a role for HuR in this effect.", "Proteasome inhibition increases HuR level, restores heat-inducible HSP72 expression and thermotolerance in WI-38 senescent human fibroblasts.", "This result is consistent with the proposed role of HuR in assisting mRNA export to the cytoplasm and in antagonizing its degradation.", "HuR immunoprecipitations were positive for RhoB mRNA indicating an in vivo association, and Western blot analysis and immunofluorescence demonstrated that HuR rapidly partitions from the nucleus to the cytoplasm after UVL", "In the cytosol, HuR is thought to function to control stability and translation of its ligand message. ", "HuR is a ligand for nuclear mRNAs containing adenylate-uridylate-rich (ARE) elements in the 3'-untranslated region.", "Once bound to the mRNA, HuR is recognized by adapter proteins that then facilitate nuclear export of the complex.", "In the cytosol, HuR is thought to function to control stability and translation of its ligand message.", "HuR is a ligand for nuclear mRNAs containing adenylate-uridylate rich elements in the 3'-untranslated region. Once bound to the mRNA, HuR is recognized by adapter proteins which then facilitate nuclear export of the complex. In the cytosol HuR is thought to function to control stability and translation of its ligand message.", "The RNA binding protein HuR regulates the stability of many target mRNAs.", "Here, we report that HuR associated with the 3' untranslated region of the mRNA encoding the longevity and stress-response protein SIRT1, stabilized the SIRT1 mRNA, and increased SIRT1 expression levels.", "In this study, we investigated the molecular mechanisms underlying the ATP analogue adenosine-5'-O-(3-thio)triphosphate-induced nucleocytoplasmic shuttling of the mRNA stabilizing factor HuR in human (h) mesangial cells (MC). ", "HuR is an essential regulator of mesenchymal responses during lung branching.", "Our data reveals HuR as the first RBP identified to play a dominant role in lung development and as a key post-transcriptional regulator of networks guiding tissue remodeling during branching morphogenesis.", "Here we demonstrated a relevance for miR-9 in HL pathogenesis and identified two new targets Dicer1 and HuR.", "We show that inhibition of miR-9 leads to derepression of DICER and HuR, which in turn results in a decrease in cytokine production by HL cells followed by an impaired ability to attract normal inflammatory cells.", "A conserved TGFβ1/HuR feedback circuit regulates the fibrogenic response in fibroblasts.", "Knockdown of HuR decreased the endogenous expression of TGFβ1 under exogenous TGFβ1 treatment, simultaneously with the decrease of Col1a, Col3a and fibronectin expression.", "Our study here established a TGFβ1/HuR feedback circuit regulating the fibrogenic response in fibroblasts, and targeting this feedback loop is of great potential to control fibrosis.", "Here, we demonstrated that increased stabilization and subsequent over-expression of HuR mRNA were coupled to TTP deficiency. These findings were observed in breast cancer cell lines with an invasive phenotype and were further confirmed in ZFP36-knockout mouse fibroblasts.", "We show that TTP-HuR imbalance correlated with increased expression of AU-rich element (ARE) mRNAs that code for cancer invasion genes.", "Here, we show that an RNA-binding protein, HuR (human antigen R), represses ARF mRNA translation, thereby maintaining the replicative life span of mouse embryonic fibroblasts (MEFs).", "The outcome of this analysis was a list of target genes regulated via HuR for their association (either increased or reduced) with the nuclear hnRNP A1-RNP complexes.", "The differentially enriched mRNAs were found to belong to GO categories relevant to biological processes anticipated for hnRNP A1 and HuR (such as transport, transcription, translation, apoptosis and cell cycle) indicating their concerted function in mRNA metabolism.", "Here, we show that overexpression of RNase L decreases cellular growth and downmodulates the RNA-binding protein, HuR, a regulator of cell-cycle progression and tumorigenesis.", "In sum, our results indicate that NO stabilizes mRNA subsets in fibroblasts, identify HuR as an RBP implicated in the NO response, reveal that HuR alone is insufficient for stabilizing several mRNAs by NO, and show that HO-1 induction by NO is regulated by HuR.", "Suppression of HuR using siRNA resulted in an attenuation of the 3T3-L1 differentiation program, consistent with HuR control of the expression of mRNA ligand(s) critical to the differentiation process.", "In mouse embryonic fibroblasts, HuR bound to and stabilized the mRNA for Mdm2, a critical negative regulator of p53.", "Our results reveal a positive feedback mechanism for the regulation of HuR, which may play an important role in the regulation of HuR during replicative senescence.", "In dividing cells, the RNA-binding protein HuR associates with and stabilizes labile mRNAs encoding proliferative proteins, events that are linked to the increased cytoplasmic presence of HuR.", "On the basis of these observations, we postulated a role for HuR in promoting the proliferation of vascular smooth muscle cells.", "We propose that HuR contributes to regulating hVSMC growth and homeostasis in pathologies associated with vascular smooth muscle proliferation.", "Antiapoptotic function of RNA-binding protein HuR effected through prothymosin alpha.", "We report the antiapoptotic effect of RNA-binding protein HuR, a critical regulator of the post-transcriptional fate of target transcripts.", "Together, our data support a regulatory scheme whereby HuR binds the ProTalpha mRNA, elevates its cytoplasmic abundance and translation, and thereby elicits an antiapoptotic program.", "CARM1 represses replicative senescence by methylating HuR and thereby enhancing HuR's ability to regulate the turnover of cyclin A, cyclin B1, c-fos, SIRT1, and p16 mRNAs.", "HuR, also known as Elavl1, is an RNA-binding protein that regulates embryonic development, progenitor cell survival, and cell stress responses.", "Together, these studies reveal an evolutionarily conserved post-transcriptional mechanism involving competitive interactions between HuR and miR-200b that controls angiogenesis.", "Immunoprecipitation of RNA-protein complexes and luciferase reporter assays indicate that HuR antagonizes the suppressive activity of miR-200b, down-regulates miR-200b expression, and promotes VEGF-A expression.", "Here we present evidence that CUGBP1 and HuR jointly regulate the translation of occludin and play a crucial role in the maintenance of tight junction (TJ) integrity in the intestinal epithelial cell monolayer.", "These findings indicate that CUGBP1 represses occludin translation by increasing occludin mRNA recruitment to P-bodies, whereas HuR promotes occludin translation by blocking occludin mRNA translocation to P-bodies via the displacement of CUGBP1.", "Through its post-transcriptional influence on specific target mRNAs, HuR can alter the cellular response to proliferative, stress, apoptotic, differentiation, senescence, inflammatory and immune stimuli.", "We focus on HuR's well-recognized implication in cancer and chronic inflammation, and discuss emerging studies linking HuR to cardiovascular, neurological, and muscular pathologies. We also discuss the progress, potential, and challenges of targeting HuR therapeutically.", "These results indicate that HuR regulates occludin mRNA translation through Chk2-dependent HuR phosphorylation and that this influence is crucial for maintenance of the epithelial barrier integrity in the intestinal tract.", "The RNA-binding protein HuR modulates the stability and translation of many target mRNAs.", "Here, we investigated the role of HuR in the regulation of occludin expression and therefore in the intestinal epithelial barrier function.", "HuR bound the 3'-untranslated region of the occludin mRNA and enhanced occludin translation.", "HuR association with the occludin mRNA depended on Chk2-dependent HuR phosphorylation. " ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/12242302", "http://www.ncbi.nlm.nih.gov/pubmed/21816340", "http://www.ncbi.nlm.nih.gov/pubmed/23837869", "http://www.ncbi.nlm.nih.gov/pubmed/11486028", "http://www.ncbi.nlm.nih.gov/pubmed/12730239", "http://www.ncbi.nlm.nih.gov/pubmed/23401122", "http://www.ncbi.nlm.nih.gov/pubmed/10673359", "http://www.ncbi.nlm.nih.gov/pubmed/23155001", "http://www.ncbi.nlm.nih.gov/pubmed/19345675", "http://www.ncbi.nlm.nih.gov/pubmed/9155038", "http://www.ncbi.nlm.nih.gov/pubmed/19884656", "http://www.ncbi.nlm.nih.gov/pubmed/17317627", "http://www.ncbi.nlm.nih.gov/pubmed/14530362", "http://www.ncbi.nlm.nih.gov/pubmed/23223443", "http://www.ncbi.nlm.nih.gov/pubmed/19289500", "http://www.ncbi.nlm.nih.gov/pubmed/15036402", "http://www.ncbi.nlm.nih.gov/pubmed/12605686", "http://www.ncbi.nlm.nih.gov/pubmed/21164076", "http://www.ncbi.nlm.nih.gov/pubmed/9860962", "http://www.ncbi.nlm.nih.gov/pubmed/16639702", "http://www.ncbi.nlm.nih.gov/pubmed/20007147", "http://www.ncbi.nlm.nih.gov/pubmed/19252527", "http://www.ncbi.nlm.nih.gov/pubmed/15824116", "http://www.ncbi.nlm.nih.gov/pubmed/10075998", "http://www.ncbi.nlm.nih.gov/pubmed/22446588", "http://www.ncbi.nlm.nih.gov/pubmed/15861128", "http://www.ncbi.nlm.nih.gov/pubmed/17288991", "http://www.ncbi.nlm.nih.gov/pubmed/9628881", "http://www.ncbi.nlm.nih.gov/pubmed/22310293", "http://www.ncbi.nlm.nih.gov/pubmed/21515253", "http://www.ncbi.nlm.nih.gov/pubmed/9763509", "http://www.ncbi.nlm.nih.gov/pubmed/22201738", "http://www.ncbi.nlm.nih.gov/pubmed/15863502", "http://www.ncbi.nlm.nih.gov/pubmed/15543229", "http://www.ncbi.nlm.nih.gov/pubmed/24152440", "http://www.ncbi.nlm.nih.gov/pubmed/23508105", "http://www.ncbi.nlm.nih.gov/pubmed/17392515", "http://www.ncbi.nlm.nih.gov/pubmed/21745814" ]

[]

[ "http://www.uniprot.org/uniprot/ELV1A_XENLA", "http://www.uniprot.org/uniprot/ELAV1_MOUSE", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005347", "http://www.uniprot.org/uniprot/ELV1B_XENLA", "http://www.uniprot.org/uniprot/ELAV1_XENTR", "http://www.uniprot.org/uniprot/ELAV1_HUMAN", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D051959" ]

[ "Baricitinib is an inhibitor of Janus kinase family of enzymes (JAKs) with selectivity for JAK1 and JAK2." ]

[ "JAK1", "JAK2" ]

[ "Reversal of Alopecia Areata Following Treatment With the JAK1/2 Inhibitor Baricitinib.", "A patient with AA was enrolled in a clinical trial to examine the efficacy of baricitinib, a JAK1/2 inhibitor, to treat concomitant CANDLE syndrome.", "Baricitinib (also known as LY3009104 or INCB028050), a novel and potent small molecule inhibitor of Janus kinase family of enzymes (JAKs) with selectivity for JAK1 and JAK2, is currently in clinical development for the treatment of rheumatoid arthritis (RA) and other inflammatory disorders.", "A patient with AA was enrolled in a clinical trial to examine the efficacy of baricitinib, a JAK1/2 inhibitor, to treat concomitant CANDLE syndrome. In vivo, preclinical studies were conducted using the C3H/HeJ AA mouse model to assess the mechanism of clinical improvement by baricitinib.", "Phase II data for four JAK inhibitors (baricitinib,", "Positive clinical trial results have also been reported for several other JAK inhibitors including baricitinib. Several other JAK inhibitors and other small molecular entities are also being developed in studies ranging from preclinical models to large clinical trials." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/24965573", "http://www.ncbi.nlm.nih.gov/pubmed/25431052", "http://www.ncbi.nlm.nih.gov/pubmed/26137574", "http://www.ncbi.nlm.nih.gov/pubmed/24818516", "http://www.ncbi.nlm.nih.gov/pubmed/23492738" ]

[]

[ "http://www.uniprot.org/uniprot/JAK2_PONAB", "http://www.uniprot.org/uniprot/JAK2_PIG", "http://www.uniprot.org/uniprot/JAK2_MOUSE", "http://www.uniprot.org/uniprot/JAK2_CHICK", "http://www.uniprot.org/uniprot/JAK2_RAT", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D053613", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D053612", "http://www.uniprot.org/uniprot/JAK2_HUMAN", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D053614" ]

[ "Yes, it has been demonstrated that triiodothyronine exerts neuroprotective properties in traumatic brain injury setting." ]

[ "yes" ]

[ "Exogenous T3 administration provides neuroprotection in a murine model of traumatic brain injury.", "Treatment with T3 (1.2μg/100g body weight, i.p.) 1h after TBI resulted in a significant improvement in motor and cognitive recovery after CCI, as well as in marked reduction of lesion volumes. ", "Western blot analysis revealed the ability of T3 to reduce brain trauma through modulation of cytoplasmic-nuclear shuttling of nuclear factor-κB (NF-κB). Twenty-four hours after brain trauma, T3-treated mice also showed significantly lower number of TUNEL(+) apoptotic neurons and curtailed induction of Bax, compared to vehicle control. In addition, T3 significantly enhanced the post-TBI expression of the neuroprotective neurotrophins (BDNF and GDNF) compared to vehicle. ", "The stimulating effect of T3 on peripheral nerve regeneration may have considerable therapeutic potential.", "The present study provides evidence that the peripheral nervous system has its own system responsible for the local production of 3,5,3'-triiodothyronine, which may play a key role during the regeneration process.", "Although it has been hypothesized that T3 may facilitate neuronal regeneration after CNS injury, the 5'-D2 response to brain injury is unknown.", "The outcome after brain injury is closely correlated with the intensity of these changes, particularly with catecholamine plasma levels and the severity of the low triiodothyronine syndrome.", "The thyroid hormones triiodothyronine (T3) and L-thyroxine appear to enhance regeneration in the peripheral and central nervous system (CNS). ", "T3 treatment influenced the general levels of incorporation of all treated groups over all days postoperation.", "T3 effects appear to involve an increased sensitivity of the cells of the injured nervous system to the hormone.", "T3, when administered over an 8 week period, stimulated axonal regeneration in the dorsal cortex and corpus callosum and promoted healing of the wound in the corpus callosum. The results of this investigation suggest that the use of T3 in the clinical treatment of injury to the central nervous system may be of less value than the work of earlier authors had indicated.", "In addition, T3 significantly enhanced the post-TBI expression of the neuroprotective neurotrophins (BDNF and GDNF) compared to vehicle" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/9681483", "http://www.ncbi.nlm.nih.gov/pubmed/11719005", "http://www.ncbi.nlm.nih.gov/pubmed/12445968", "http://www.ncbi.nlm.nih.gov/pubmed/6798220", "http://www.ncbi.nlm.nih.gov/pubmed/23313345", "http://www.ncbi.nlm.nih.gov/pubmed/23601250", "http://www.ncbi.nlm.nih.gov/pubmed/839237", "http://www.ncbi.nlm.nih.gov/pubmed/7804793" ]

[]

[]

[ "When subjected to pressure overload, mTOR-ablated mice demonstrated an impaired hypertrophic response and accelerated heart failure progression. Thus, mTOR complex 1 signaling plays an important role in myocardial response to stress, to regulate cardiomyocyte viability and heart failure." ]

[]

[ "Myocardial MTOR activity changes during hypertrophy and heart failure (HF).", "When subjected to pressure overload, Mtor-ablated mice demonstrated an impaired hypertrophic response and accelerated HF progression.", "Our results demonstrate a role for the MTORC1 signaling network in the myocardial response to stress. In particular, they highlight the role of 4E-BP1 in regulating cardiomyocyte viability and in HF. Because the effects of reduced MTOR activity were mediated through increased 4E-BP1 inhibitory activity, blunting this mechanism may represent a novel therapeutic strategy for improving cardiac function in clinical HF." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/20644257" ]

[]

[ "http://www.disease-ontology.org/api/metadata/DOID:11984", "http://www.uniprot.org/uniprot/MTOR_HUMAN", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D054144", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D006321", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D006333", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D058570", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009206", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D002312", "http://www.disease-ontology.org/api/metadata/DOID:9775" ]

[ "Yes. Lysine-specific demethylase 1 restricts hematopoietic progenitor proliferation and is essential for terminal differentiation of erythroid, granulomonocytic and megakaryocytic progenitors." ]

[ "yes" ]

[ "Histone lysine-specific demethylase 1 (LSD1) protein is involved in Sal-like protein 4 (SALL4)-mediated transcriptional repression in hematopoietic stem cells", "shRNA-mediated knockdown of LSD1 in hematopoietic precursor cells resulted in altered SALL4 downstream gene expression and increased cellular activity", "our data revealed that histone demethylase LSD1 may negatively regulate SALL4-mediated transcription, and the dynamic regulation of SALL4-associated epigenetic factors cooperatively modulates early hematopoietic precursor proliferation", "Lysine-specific demethylase 1 restricts hematopoietic progenitor proliferation and is essential for terminal differentiation", " LSD1 represents a central regulator of hematopoietic stem and progenitor cells", " LSD1-kd led to an extensive expansion of granulomonocytic, erythroid and megakaryocytic progenitors", "LSD1-kd was associated with the upregulation of key hematopoietic genes", "our findings distinguish LSD1 as a critical regulator of hematopoiesis", "A short Gfi-1B isoform controls erythroid differentiation by recruiting the LSD1-CoREST complex through the dimethylation of its SNAG domain", "Dynamic interaction between TAL1 oncoprotein and LSD1 regulates TAL1 function in hematopoiesis and leukemogenesis", "Here, we reported that protein kinase A (PKA)-mediated phosphorylation regulates TAL1 interaction with the lysine-specific demethylase (LSD1) that removes methyl group from methylated Lys 4 on histone H3 tails. Phosphorylation of serine 172 in TAL1 specifically destabilizes the TAL1-LSD1 interaction leading to promoter H3K4 hypermethylation and activation of target genes that have been suppressed in normal and malignant hematopoiesis", "LSD1-mediated epigenetic modification is required for TAL1 function and hematopoiesis", "we show that TAL1 is associated with histone demethylase complexes containing lysine-specific demethylase 1 (LSD1), RE1 silencing transcription factor corepressor (CoREST), histone deacetylase 1 (HDAC1), and histone deacetylase 2 in erythroleukemia and T cell leukemia cells", "we demonstrate that the TAL1-associated LSD1, HDAC1, and their enzymatic activities are coordinately down-regulated during the early phases of erythroid differentiation", "TAL1 recruits LSD1 to the silenced p4.2 promoter in undifferentiated, but not in differentiated, murine erythroleukemia (MEL) cells", "the dynamic regulation of TAL1-associated LSD1/HDAC1 complex may determine the onset of erythroid differentiation programs", "Epigenetic regulation of hematopoietic differentiation by Gfi-1 and Gfi-1b is mediated by the cofactors CoREST and LSD1", "Inhibition of CoREST and LSD1 perturbs differentiation of erythroid, megakaryocytic, and granulocytic cells as well as primary erythroid progenitors", "we show that chromatin regulatory proteins CoREST and LSD1 mediate transcriptional repression by Gfi proteins. Lineage-restricted deployment of these cofactors through interaction with Gfi proteins controls hematopoietic differentiation", "Taken together, our findings distinguish LSD1 as a critical regulator of hematopoiesis and point to severe, but reversible, side effects of a LSD1-targeted therapy.", "LSD1-mediated epigenetic modification is required for TAL1 function and hematopoiesis.", "Dynamic interaction between TAL1 oncoprotein and LSD1 regulates TAL1 function in hematopoiesis and leukemogenesis.", "Phosphorylation of serine 172 in TAL1 specifically destabilizes the TAL1-LSD1 interaction leading to promoter H3K4 hypermethylation and activation of target genes that have been suppressed in normal and malignant hematopoiesis.", "Histone lysine-specific demethylase 1 (LSD1) protein is involved in Sal-like protein 4 (SALL4)-mediated transcriptional repression in hematopoietic stem cells.", "Taken together, our findings distinguish LSD1 as a critical regulator of hematopoiesis and point to severe, but reversible, side effects of a LSD1-targeted therapy." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/19497860", "http://www.ncbi.nlm.nih.gov/pubmed/19736520", "http://www.ncbi.nlm.nih.gov/pubmed/22699452", "http://www.ncbi.nlm.nih.gov/pubmed/22801375", "http://www.ncbi.nlm.nih.gov/pubmed/23795291", "http://www.ncbi.nlm.nih.gov/pubmed/22310283", "http://www.ncbi.nlm.nih.gov/pubmed/17707228", "http://www.ncbi.nlm.nih.gov/pubmed/23147254", "http://www.ncbi.nlm.nih.gov/pubmed/24163373", "http://www.ncbi.nlm.nih.gov/pubmed/22399799" ]

[]

[ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0035162", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0030097", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0033193" ]

[ "Ubiquitination is best known for its role in targeting proteins for degradation by the proteasome, but evidence of the nonproteolytic functions of ubiquitin is also rapidly accumulating. One example of the regulatory, rather than proteolytic, function of ubiquitin is provided by study of the tumor necrosis factor (TNF) receptor-associated factor (TRAF) proteins, which function as ubiquitin ligases to synthesize lysine 63 (K(63))-linked polyubiquitin chains to mediate protein kinase activation through a proteasome-independent mechanism. Some TRAF proteins, such as TRAF2 and TRAF3, have recently been shown to have a positive role in the canonical pathway that activates nuclear factor kappaB (NF-kappaB) through IkappaB kinase beta (IKKbeta), but a negative role in the noncanonical pathway that activates NF-kappaB through IKKalpha. These opposing roles of TRAF proteins may be linked to their ability to synthesize distinct forms of polyubiquitin chains. Indeed, the TRAF2-interacting protein RIP can mediate IKK activation when it is modified by K(63) polyubiquitin chains, but is targeted to degradation by the proteasome when it is K(48)-polyubiquitinted by the NF-kappaB inhibitor A20. Thus, ubiquitin chains are dynamic switches that can influence signaling outputs in dramatically different ways.In contrast to K48-linked polyubiquitin chains, K63-linked polyubiquitin chains function in nonproteasomal biological processes.", "In contrast to K48-linked polyubiquitin chains, K63-linked polyubiquitin chains function in nonproteasomal biological processes. Modification of proteins by the addition of lysine (K)-63-linked polyubiquitin (polyUb) chains is suggested to play important roles in a variety of cellular events, including DNA repair, signal transduction, and receptor endocytosis. One example of the regulatory, rather than proteolytic, function of ubiquitin is provided by study of the tumor necrosis factor (TNF) receptor-associated factor (TRAF) proteins, which function as ubiquitin ligases to synthesize lysine 63 (K(63))-linked polyubiquitin chains to mediate protein kinase activation through a proteasome-independent mechanism.", "One example of the regulatory, rather than proteolytic, function of ubiquitin is provided by study of the tumor necrosis factor (TNF) receptor-associated factor (TRAF) proteins, which function as ubiquitin ligases to synthesize lysine 63 (K(63))-linked polyubiquitin chains to mediate protein kinase activation through a proteasome-independent mechanism", "Modification of proteins by the addition of lysine (K)-63-linked polyubiquitin (polyUb) chains is suggested to play important roles in a variety of cellular events, including DNA repair, signal transduction, and receptor endocytosis. In contrast to K48-linked polyubiquitin chains, K63-linked polyubiquitin chains function in nonproteasomal biological processes." ]

[ "no" ]

[ "In contrast to K48-linked polyubiquitin chains, K63-linked polyubiquitin chains function in nonproteasomal biological processes.", "Modification of proteins by the addition of lysine (K)-63-linked polyubiquitin (polyUb) chains is suggested to play important roles in a variety of cellular events, including DNA repair, signal transduction, and receptor endocytosis. ", "Ubiquitination is best known for its role in targeting proteins for degradation by the proteasome, but evidence of the nonproteolytic functions of ubiquitin is also rapidly accumulating. One example of the regulatory, rather than proteolytic, function of ubiquitin is provided by study of the tumor necrosis factor (TNF) receptor-associated factor (TRAF) proteins, which function as ubiquitin ligases to synthesize lysine 63 (K(63))-linked polyubiquitin chains to mediate protein kinase activation through a proteasome-independent mechanism. Some TRAF proteins, such as TRAF2 and TRAF3, have recently been shown to have a positive role in the canonical pathway that activates nuclear factor kappaB (NF-kappaB) through IkappaB kinase beta (IKKbeta), but a negative role in the noncanonical pathway that activates NF-kappaB through IKKalpha. These opposing roles of TRAF proteins may be linked to their ability to synthesize distinct forms of polyubiquitin chains. Indeed, the TRAF2-interacting protein RIP can mediate IKK activation when it is modified by K(63) polyubiquitin chains, but is targeted to degradation by the proteasome when it is K(48)-polyubiquitinted by the NF-kappaB inhibitor A20. Thus, ubiquitin chains are dynamic switches that can influence signaling outputs in dramatically different ways.", "Importantly, although Lys-48-linked ubiquitin chains appear to trigger proteasomal degradation, the presence of Lys-63-linked ubiquitin chains suggests that ubiquitination of IP(3)Rs may have physiological consequences beyond signaling for degradation.", "Chains of ubiquitin linked via lysine 48 (K48) are associated with protein degradation while chains linked via lysine 63 (K63) are associated with intracellular signaling.", "Lys(48)-linked chains target proteins for proteasomal degradation, and Lys(63)-linked chains function in signal transduction, endocytosis and DNA repair", "Remarkably, the attached Lys-48- and Lys-63-linked ubiquitin chains are homogeneous and are segregated to separate IP(3)R subunits, and Lys-48-linked ubiquitin chains, but not Lys-63-linked chains, are required for IP(3)R degradation", "Activated inositol 1,4,5-trisphosphate receptors are modified by homogeneous Lys-48- and Lys-63-linked ubiquitin chains, but only Lys-48-linked chains are required for degradation." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/18042044", "http://www.ncbi.nlm.nih.gov/pubmed/21737094", "http://www.ncbi.nlm.nih.gov/pubmed/19091944", "http://www.ncbi.nlm.nih.gov/pubmed/21071436", "http://www.ncbi.nlm.nih.gov/pubmed/15728425", "http://www.ncbi.nlm.nih.gov/pubmed/20663875" ]

[]

[ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0061136", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0016567", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0010498" ]

[ "Yes. Recent data support the view that transcription factors - in particular, homeoproteins - can be transferred from cell to cell and have direct non-cell-autonomous (and therefore paracrine) activities.", "Pax6 is a transcription factor essential for the development of tissues including the eyes, central nervous system and endocrine glands of vertebrates and invertebrates. It regulates the expression of a broad range of molecules, including transcription factors, cell adhesion and short-range cell-cell signalling molecules, hormones and structural proteins" ]

[ "yes" ]

[ "Pax6 is a transcription factor essential for the development of tissues including the eyes, central nervous system and endocrine glands of vertebrates and invertebrates. It regulates the expression of a broad range of molecules, including transcription factors, cell adhesion and short-range cell-cell signalling molecules, hormones and structural proteins", "Recent data support the view that transcription factors - in particular, homeoproteins - can be transferred from cell to cell and have direct non-cell-autonomous (and therefore paracrine) activities" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/14570063", "http://www.ncbi.nlm.nih.gov/pubmed/12386935" ]

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[ "http://amigo.geneontology.org/amigo/term/GO:0007267", "http://amigo.geneontology.org/amigo/term/GO:0006351", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D014157" ]

[ "aptamers\nenzymes\nstreptavidin\nconcanavalin A\ncarboxylic-modified \nTiO2\nantibodies\nSELEX library\nsynthesized DNA\nC18\nC8\noligo(dT)" ]

[ "aptamers", "enzymes", "streptavidin", "concanavalin A", "carboxylic-modified", "TiO2", "antibodies", "SELEX library", "synthesized DNA", "C18", "C8", "oligo(dT)" ]

[ "aptamer-based magnetic separation system ", "enzymes coated to magnetic beads", " Aptamers are short, single-stranded (ss) oligonucleotidesable to recognize target molecules with high affinity. ", " Recent developments involve immobilization of tagged enzymes onto magnetic nanoparticles. ", "Using magnetic beads to immobilize DNAs containing various types of structures, we evaluated the in vitro binding activities of two well-characterized DNA repair proteins, Escherichia coli MutS and human p53.", "An affinity capture involved enzymatic assay for thrombin by using peptide aptamers as affinity ligands on magnetic beads", "During phage selection the biotinylated antigens are bound to streptavidin coupled magnetic beads, ", " aptamer-functionalized magnetic beads ", "native antibody immobilized to magnetic beads", "Plasma membrane isolation using immobilized concanavalin A magnetic beads.", "streptavidin magnetic beads", " Digoxin was coated onto the surface of streptavidin magnetic beads. ", "covalent immobilization of the antigen onto carboxylic-modified magnetic beads (HOOC-MBs) activated with N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide (EDC) and N-hydroxysulfosuccinimide (sulfo-NHS), and further incubation in a mixture solution containing variable concentrations of the antigen and a fixed concentration of an HRP-labeled detection antibody. ", "Aptamers against HNE were immobilized on magnetic beads", "The high specificity was obtained by using the magnetic beads and aptamers,", "Multiple targets (maltase, invertase, lipase) were immobilized on the magnetic beads by covalent linkage using 1-(3-dimethyl-aminopropyl)-3-ethyl-carbodiimide (EDC) and N-hydroxysuccinimide (NHS) as reaction reagents, respectively.", "TiO2 -coated magnetic beads", "antibody-targeted magnetic beads", "A special SELEX library was constructed with the aim to immobilize this library on magnetic beads", "streptavidin-coupled magnetic beads", "aptamers loaded on the magnetic beads ", "His-affinity magnetic beads", "treptavidin-coated magnetic beads", ", synthesized DNA is bound to magnetic beads", "streptavidin-modified magnetic microbeads ", "oligo(dT) magnetic beads" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/23326761", "http://www.ncbi.nlm.nih.gov/pubmed/22903707", "http://www.ncbi.nlm.nih.gov/pubmed/23176741", "http://www.ncbi.nlm.nih.gov/pubmed/23143268", "http://www.ncbi.nlm.nih.gov/pubmed/23021809", "http://www.ncbi.nlm.nih.gov/pubmed/23746403", "http://www.ncbi.nlm.nih.gov/pubmed/23149231", "http://www.ncbi.nlm.nih.gov/pubmed/22796092", "http://www.ncbi.nlm.nih.gov/pubmed/23401153", "http://www.ncbi.nlm.nih.gov/pubmed/23928048", "http://www.ncbi.nlm.nih.gov/pubmed/23877419", "http://www.ncbi.nlm.nih.gov/pubmed/23971905", "http://www.ncbi.nlm.nih.gov/pubmed/24291643", "http://www.ncbi.nlm.nih.gov/pubmed/23501439", "http://www.ncbi.nlm.nih.gov/pubmed/24224000", "http://www.ncbi.nlm.nih.gov/pubmed/23411631", "http://www.ncbi.nlm.nih.gov/pubmed/22841112", "http://www.ncbi.nlm.nih.gov/pubmed/23850993", "http://www.ncbi.nlm.nih.gov/pubmed/23845492", "http://www.ncbi.nlm.nih.gov/pubmed/23174509", "http://www.ncbi.nlm.nih.gov/pubmed/23934803", "http://www.ncbi.nlm.nih.gov/pubmed/24148457", "http://www.ncbi.nlm.nih.gov/pubmed/23378340", "http://www.ncbi.nlm.nih.gov/pubmed/23540244", "http://www.ncbi.nlm.nih.gov/pubmed/23598134", "http://www.ncbi.nlm.nih.gov/pubmed/23257838" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D059346", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D008280" ]

[ "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." ]

[ "no" ]

[ "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.", "The lack of specific randomized trials enrolling either old or very old subjects, aimed at evaluate the efficacy of hormonal replacement on overall survival and cardiovascular risk reduction along with the negative effects of possible over-treatment, makes the decision to treat older people a still unresolved clinical challenge", "In patients with type 2 DM, the presence of SH serves as an additional risk factor for endothelial dysfunction.", "Treatment of SCH with levothyroxine was associated with fewer IHD events in younger individuals, but this was not evident in older people.", "Subclinical hyperthyroidism seems to be a risk factor of developing major cardiovascular events, especially stroke in older adults from the general population with normal left ventricular function.", "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.", "In CHF patients TSH levels even slightly above normal range are independently associated with a greater likelihood of heart failure progression.", "In current RCTs, levothyroxine replacement therapy for subclinical hypothyroidism did not result in improved survival or decreased cardiovascular morbidity. Data on health-related quality of life and symptoms did not demonstrate significant differences between intervention groups.", "However, the actual effectiveness of thyroid hormone substitution in reducing the risk of cardiovascular events remains to be elucidated. In conclusion, the multiplicity and the possible reversibility of subclinical hypothyroidism-associated cardiovascular abnormalities suggest that the decision to treat a patient should depend on the presence of risk factors, rather than on a TSH threshold. ", "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/20807695", "http://www.ncbi.nlm.nih.gov/pubmed/16259335", "http://www.ncbi.nlm.nih.gov/pubmed/23559085", "http://www.ncbi.nlm.nih.gov/pubmed/16542047", "http://www.ncbi.nlm.nih.gov/pubmed/22529180", "http://www.ncbi.nlm.nih.gov/pubmed/16026106", "http://www.ncbi.nlm.nih.gov/pubmed/23369134", "http://www.ncbi.nlm.nih.gov/pubmed/17636722", "http://www.ncbi.nlm.nih.gov/pubmed/19463607", "http://www.ncbi.nlm.nih.gov/pubmed/21823062", "http://www.ncbi.nlm.nih.gov/pubmed/23252247", "http://www.ncbi.nlm.nih.gov/pubmed/19006851" ]

[]

[ "http://www.disease-ontology.org/api/metadata/DOID:114", "http://www.disease-ontology.org/api/metadata/DOID:1459", "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=D016896", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D007037" ]

[ "Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT) can cause sudden cardiac death." ]

[ "yes" ]

[ "Two siblings died suddenly at the ages of 9 and 10 years", "Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a type of cardiac arrhythmia that occurs in people with a structurally normal heart. Stress or anxiety-induced release of endogenous catecholamines causes a dysfunction in the myocytic calcium-ion channel, leading to ventricular arrhythmias that can cause dizziness, syncope, or sudden cardiac death. ", "During a follow-up of 48±94 months, arrhythmia events (sudden cardiac death and aborted cardiac arrest) associated with noncompliance occurred in 2 patients. ", "We report a family with repeat events of sudden cardiac death and recurrent ventricular fibrillation in a teenage girl, where autopsy data and clinical investigations were inconclusive. The diagnosis of catecholaminergic polymorphic ventricular tachycardia (CPVT) was established only following finding a gene mutation in the cardiac ryanodine receptor. ", "Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a devastating inherited disorder characterized by episodic syncope and/or sudden cardiac arrest during exercise or acute emotion in individuals without structural cardiac abnormalities. Although rare, CPVT is suspected to cause a substantial part of sudden cardiac deaths in young individuals. ", "catecholaminergic polymorphic ventricular tachycardia (CPVT), and Brugada syndrome (BrS), leave no evidence to be found at autopsy", "a spectrum of sudden cardiac death (SCD)-predisposing heritable cardiac arrhythmia syndromes, including long QT syndrome (LQTS), short QT syndrome (SQTS), Brugada syndrome (BrS), and catecholaminergic polymorphic ventricular tachycardia (CPVT). ", "CPVT is a familial arrhythmogenic syndrome characterized by abnormal calcium (Ca(2+)) handling, ventricular arrhythmias, and sudden cardiac death", "Mutations in RyR2 are linked to catecholaminergic polymorphic ventricular tachycardia (CPVT) and sudden cardiac death.", "Patients with CPVT often present with exercise- or emotion induced syncope, the first presentation can also be sudden cardiac death.", "Among the five major arrhythmogenic disorders occurring in the absence of a structural heart disease is catecholaminergic polymorphic ventricular tachycardia (CPVT), which is a highly lethal form of inherited arrhythmias. ", "Patients with CPVT are at high risk of developing life-threatening ventricular arrhythmias when untreated. ", "Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited arrhythmia syndrome characterized by VT induced by adrenergic stress in the absence of structural heart disease and high incidence of sudden cardiac death. ", "CPVT is an inherited arrhythmia syndrome caused by gene mutations that destabilize cardiac ryanodine receptor Ca(2+) release channels. Sudden cardiac death is incompletely prevented by conventional drug therapy with β-blockers with or without Ca(2+) channel blockers. ", "Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited arrhythmogenic disease that can cause sudden cardiac death due to ventricular fibrillation (VF).", "Important potential causes of sudden cardiac deaths in the absence of heart disease are primary electrical diseases such as Brugada syndrome, long QT syndrome (LQTS), short QT syndrome and catecholaminergic polymorphic ventricular tachyarrhythmias. ", "catecholaminergic polymorphic ventricular tachycardia (CPVT), and Brugada syndrome (BrS) are primary inherited arrhythmia syndromes that may cause syncope and sudden cardiac death in young individuals. ", "Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a cardiac channelopathy characterized by altered intracellular calcium handling resulting in ventricular arrhythmias and high risk of cardiac sudden death in young cases with normal structural hearts. ", "Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited arrhythmogenic disorder that causes syncopal episodes related with stress or emotion and even sudden cardiac deaths.", "Catecholaminergic polymorphic ventricular tachycardia caused by mutations in the RyR2 gene manifests as severe arrhythmias, and may provide a candidate for sudden cardiac deaths.", "Patients diagnosed with an electrical cardiomyopathy have an increased risk of syncope and sudden cardiac death (SCD). ", "Patients with CPVT present with exercise-induced syncope and sudden cardiac death but normal resting electrocardiograms. ", "Over 80% of SCD occurs in patients with organic heart disease. However, approximately 10-15% of SCD occurs in the presence of structurally normal heart and the majority of those patients are young. In this group of patients, changes in genes encoding cardiac ion channels produce modification of the function of the channel resulting in an electrophysiological substrate of VA and SCD. Collectively these disorders are referred to as Cardiac Ion Channelopathies. The 4 major syndromes in this group are: The Long QT Syndrome (LQTS), the Brugada Syndrome (BrS), the Short QT Syndrome (SQTS), and the Catecholaminergic Polymorphic VT (CPVT). ", "Important potential causes of sudden cardiac deaths in the absence of heart disease are primary electrical diseases such as Brugada syndrome, long QT syndrome (LQTS), short QT syndrome (SQTS), and catecholaminergic polymorphic ventricular tachyarrhythmias (CPVT). ", "Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a familial cardiac arrhythmia that is related to RYR2 or CASQ2 gene mutation. It occurs in patients with structurally normal heart and causes exercise-emotion-triggered syncope and sudden cardiac death.", "Potentially lethal ion channel disorders (channelopathies) such as the long QT syndromes (LQTS), catecholaminergic polymorphic ventricular tachycardia (CPVT)", "Aberrant spontaneous, diastolic Ca2+ leak from the SR due to dysfunctional RyR2 contributes to the formation of delayed after-depolarisations, which are thought to underlie the fatal arrhythmia that occurs in both heart failure (HF) and in catecholaminergic polymorphic ventricular tachycardia (CPVT). ", "Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an uncommon heritable disease presenting with syncope or sudden cardiac death.", "Mutations in RyR2 have been linked to exercise-induced sudden cardiac death (catecholaminergic polymorphic ventricular tachycardia [CPVT]).", "Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a heritable arrhythmia unmasked by exertion or stress, characterized by triggered activity and sudden cardiac death in affected patients.", "families that exhibit CPVT (catecholaminergic polymorphic ventricular tachycardia), a condition in which physical or emotional stress can trigger severe tachyarrhythmias that can lead to sudden cardiac death.", "that often leads to sudden death in HF and in CPVT.", "Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited disease characterized by adrenergically mediated polymorphic ventricular tachycardia leading to syncope and sudden cardiac death.", "Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an autosomal dominant inherited disorder characterized by adrenergic induced polymorphic ventricular tachycardias and associated with sudden cardiac death. ", "These data suggest that \"leaky\" RyR2 channels can trigger fatal cardiac arrhythmias, providing a possible explanation for CPVT.", "Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a rare arrhythmogenic disorder characterized by syncopal events and sudden cardiac death at a young age during physical stress or emotion, in the absence of structural heart disease. ", " catecholaminergic polymorphic ventricular tachycardia (CPVT), idiopathic ventricular fibrillation (VF), and arrhythmogenic right ventricular cardiomyopathy (ARVC) account for a relevant proportion of sudden cardiac death cases in young patients cohorts. ", "has recently been shown to be involved in at least two forms of sudden cardiac death (SCD): (1) Catecholaminergic polymorphic ventricular tachycardia (CPVT) " ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/19564966", "http://www.ncbi.nlm.nih.gov/pubmed/24076290", "http://www.ncbi.nlm.nih.gov/pubmed/22119737", "http://www.ncbi.nlm.nih.gov/pubmed/18684293", "http://www.ncbi.nlm.nih.gov/pubmed/19601860", "http://www.ncbi.nlm.nih.gov/pubmed/21135804", "http://www.ncbi.nlm.nih.gov/pubmed/15890976", "http://www.ncbi.nlm.nih.gov/pubmed/18483626", "http://www.ncbi.nlm.nih.gov/pubmed/19575158", "http://www.ncbi.nlm.nih.gov/pubmed/19568611", "http://www.ncbi.nlm.nih.gov/pubmed/19631908", "http://www.ncbi.nlm.nih.gov/pubmed/20513597", "http://www.ncbi.nlm.nih.gov/pubmed/17959506", "http://www.ncbi.nlm.nih.gov/pubmed/24011300", "http://www.ncbi.nlm.nih.gov/pubmed/22995932", "http://www.ncbi.nlm.nih.gov/pubmed/20091251", "http://www.ncbi.nlm.nih.gov/pubmed/19781797", "http://www.ncbi.nlm.nih.gov/pubmed/21616285", "http://www.ncbi.nlm.nih.gov/pubmed/22524859", "http://www.ncbi.nlm.nih.gov/pubmed/20143088", "http://www.ncbi.nlm.nih.gov/pubmed/22050625", "http://www.ncbi.nlm.nih.gov/pubmed/21893508", "http://www.ncbi.nlm.nih.gov/pubmed/22307399", "http://www.ncbi.nlm.nih.gov/pubmed/22993115", "http://www.ncbi.nlm.nih.gov/pubmed/21872879", "http://www.ncbi.nlm.nih.gov/pubmed/19345240", "http://www.ncbi.nlm.nih.gov/pubmed/22749309", "http://www.ncbi.nlm.nih.gov/pubmed/23286974", "http://www.ncbi.nlm.nih.gov/pubmed/12837242", "http://www.ncbi.nlm.nih.gov/pubmed/23040497", "http://www.ncbi.nlm.nih.gov/pubmed/12574890", "http://www.ncbi.nlm.nih.gov/pubmed/20361477", "http://www.ncbi.nlm.nih.gov/pubmed/15749201", "http://www.ncbi.nlm.nih.gov/pubmed/17052226", "http://www.ncbi.nlm.nih.gov/pubmed/21292648", "http://www.ncbi.nlm.nih.gov/pubmed/11807805", "http://www.ncbi.nlm.nih.gov/pubmed/23094885", "http://www.ncbi.nlm.nih.gov/pubmed/12386154" ]

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[ "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=D013610", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D017180" ]

[ "DNA topoisomerase II inhibitors eliminate cancer cells by causing DNA double-strand breaks, finally leading to apoptotic cell death. Moreover, drug-induced histone eviction was also shown to be associated with attenuated DNA repair, epigenetic changes and transcpription deregulation." ]

[]

[ "DNA topoisomerase II inhibitors are a major class of cancer chemotherapeutics, which are thought to eliminate cancer cells by inducing DNA double-strand breaks.", "We show that anthracyclines promote histone eviction irrespective of their ability to induce DNA double-strand breaks. The histone variant H2AX, which is a key component of the DNA damage response, is also evicted by anthracyclines, and H2AX eviction is associated with attenuated DNA repair.", "Induction of apoptotic cell death by DNA topoisomerase II inhibitors", "The results we have obtained clearly indicate that topoisomerase II poisons induce cell death by apoptosis.", "Histone eviction deregulates the transcriptome in cancer cells", "We define a novel mechanism of action of anthracycline anticancer drugs doxorubicin and daunorubicin on chromatin biology, with important consequences for DNA damage responses, epigenetics, transcription" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/23715267", "http://www.ncbi.nlm.nih.gov/pubmed/8824770" ]

[]

[ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0008657", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D059003", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0003918", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D059005", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0003916", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0008156", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:2000371", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004250", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D026942" ]

[ "Yes, some HDAC inhibitors, such as Vorinostat, are on trial for human treatment after proving successful in animal models. Combination with other drugs is likely to be needed to control metastasis." ]

[ "yes" ]

[ "JNJ-26481585 also fully inhibited the growth of C170HM2 colorectal liver metastases, whereas again 5-fluorouracil/Leucovorin showed modest activity.", "Although not meeting the RECIST response criteria for adequate single-agent activity, the observed tolerable toxicities and the potential for clinical benefit in terms of stable disease suggest that further assessment of vorinostat as a part of combination therapy with either chemotherapeutic or targeted agents in metastatic breast might be undertaken.", "Treatments of different structural classes of HDACi simultaneously induced cell death and promoted cell migration and metastasis in multiple cancer cell types. Suppression of HDACi-induced PKCs leads to development of low toxic and long-term therapeutic strategies to potentially treat cancer as a chronic disease.", "mRNA expression analysis of lung tumor bearing mice suggested that the enhanced chemopreventive activity of the combination is related to atorvastatin modulation of DNA repair, SAHA modulation of angiogenesis, and both drugs modulating invasion and metastasis pathways.", "Histone deacetylase (HDAC) inhibitors induced morphologic differentiation, cell-cycle exit, and a shift to a differentiated, melanocytic gene expression profile in cultured UM cells. VPA inhibited the growth of UM tumors in vivo.", "When both drugs were used in concert additive effects were observed on the migratory and invasive behavior but not on tumor-endothelium and tumor-matrix interaction. Separate mTOR or HDAC inhibition slows processes related to tumor metastasis. The RAD001-VPA combination showed advantage over VPA monotreatment with particular respect to migration and invasion.", "In conclusion, sequential treatments of mice with MS-275 followed by TRAIL may target multiple pathways to reverse EMT and inhibit tumor progression, angiogenesis, and metastasis and represent a novel therapeutic approach to treat cancer.", "In vivo, AA98 synergized with vorinostat to inhibit tumor growth and metastasis.", "We report the first preclinical data for the prevention of brain metastasis of triple-negative breast cancer. Vorinostat is brain permeable and can prevent the formation of brain metastases by 62%. Its mechanism of action involves the induction of DNA double-strand breaks, suggesting rational combinations with DNA active drugs or radiation.", "Combining vorinostat with radiation may be a potential treatment option for patients with breast cancer who develop brain metastases.", "Although single-agent PCI-24781 had modest effects on STS growth and metastasis, marked inhibition was observed when combined with chemotherapy.", "In a 4T1 metastatic breast carcinoma model, AN-7 inhibited the formation of lung lesions by 76% and AN-9 by 47%, further demonstrating the greater efficacy of AN-7 compared to AN-9 (P<0.02). Both AN-7 and AN-9 exhibited antimetastatic and antiangiogenic activities by reducing vascularization, bFGF expression and HIF-1alpha.", "Since prolonged oral administration with 50 mg/kg or a single oral dose of 1.2 g/kg AN-7 did not cause adverse effects and the former exhibited significant anticancer activity, AN-7 is likely to display a high therapeutic index and may be beneficial for prostate cancer patients.", "We show that apicidin significantly inhibits H-ras-induced invasive phenotype of MCF10A human breast epithelial cells in parallel with a specific downregulation of matrix metalloproteinase (MMP)-2, but not MMP-9. We also show that apicidin induces a morphological reversal and growth inhibition of H-ras MCF10A cells similar to that induced by other HDAC inhibitors.", "We also found that NaB induced three genes, which are known metastatic suppressors, and downregulated 11 genes, which have been shown to promote metastasis." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/19417021", "http://www.ncbi.nlm.nih.gov/pubmed/20884621", "http://www.ncbi.nlm.nih.gov/pubmed/22279574", "http://www.ncbi.nlm.nih.gov/pubmed/21041383", "http://www.ncbi.nlm.nih.gov/pubmed/22038994", "http://www.ncbi.nlm.nih.gov/pubmed/22811583", "http://www.ncbi.nlm.nih.gov/pubmed/10893438", "http://www.ncbi.nlm.nih.gov/pubmed/18506586", "http://www.ncbi.nlm.nih.gov/pubmed/15800932", "http://www.ncbi.nlm.nih.gov/pubmed/21452015", "http://www.ncbi.nlm.nih.gov/pubmed/19789319", "http://www.ncbi.nlm.nih.gov/pubmed/19509253", "http://www.ncbi.nlm.nih.gov/pubmed/18981013", "http://www.ncbi.nlm.nih.gov/pubmed/19861438", "http://www.ncbi.nlm.nih.gov/pubmed/22161747", "http://www.ncbi.nlm.nih.gov/pubmed/15318170" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D056572" ]

[ "The skeletal muscle LIM protein 1 (SLIM1) is highly expressed in skeletal and cardiac muscle, and its expression is downregulated significantly in dilated human cardiomyopathy. Loss of murine MLP results in dilated cardiomyopathy, and mutations in human MLP lead to cardiac hypertrophy, indicating a critical role for MLP in maintaining normal cardiac function.", "Yes, Muscle LIM protein is involved in cardiomyopathies. In specific, the skeletal muscle LIM protein 1 (SLIM1) is highly expressed in skeletal and cardiac muscle, and its expression is downregulated significantly in dilated human cardiomyopathy. Mutations in the human MLP gene are associated with hypertrophic and dilated cardiomyopathy. MLP became an important model for experimental cardiology when it was first demonstrated that MLP deficiency leads to myocardial hypertrophy followed by a dilated cardiomyopathy and heart failure phenotype." ]

[ "yes" ]

[ "Muscle LIM protein (MLP) has been proposed to be a central player in the pathogenesis of heart muscle disease. In line with this notion, the homozygous loss of MLP results in cardiac hypertrophy and dilated cardiomyopathy. Moreover, MLP is induced in several models of cardiac hypertrophy such as aortic banding and myocardial infarction. ", "Muscle LIM protein (MLP) null mice are often used as a model for human dilated cardiomyopathy.", "A lack of MLP leads to an age-dependent impairment of excitation-contraction coupling with resulting contractile dysfunction and secondary fibrosis.", "Loss of murine MLP results in dilated cardiomyopathy, and mutations in human MLP lead to cardiac hypertrophy, indicating a critical role for MLP in maintaining normal cardiac function.", "Our data indicate that MLP contributes to muscle stiffness and is necessary for maximum work and power generation.", "Interestingly, MLP was also found to be down-regulated in humans with heart failure (Zolk et al. Circulation 101:2674-2677, 2000) and MLP mutations are able to cause hypertrophic and dilated forms of cardiomyopathy in humans (Bos et al. Mol Genet Metab 88:78-85, 2006; Geier et al. Circulation 107:1390-1395, 2003; Hershberger et al. Clin Transl Sci 1:21-26, 2008; Knöll et al. Cell 111:943-955, 2002; Knöll et al. Circ Res 106:695-704, 2010; Mohapatra et al. Mol Genet Metab 80:207-215, 2003).", "MLP soon became an important model for experimental cardiology when it was first demonstrated that MLP deficiency leads to myocardial hypertrophy followed by a dilated cardiomyopathy and heart failure phenotype (Arber et al. Cell 88:393-403, 1997). ", "Previous studies have shown an association between CSRP3 missense mutations and either dilated cardiomyopathy (DCM) or HCM, but all these studies were unable to provide comprehensive genetic evidence for a causative role of CSRP3 mutations. ", "We used a newly designed monoclonal antibody to show that muscle LIM protein (MLP), the protein encoded by CSRP3, is mainly a cytosolic component of cardiomyocytes and not tightly anchored to sarcomeric structures. Our functional data from both in vitro and in vivo analyses suggest that at least one of MLP's mutated forms seems to be destabilized in the heart of HCM patients harbouring a CSRP3 missense mutation.", "Muscle LIM protein (MLP) is a cytoskeletal protein located at the Z-disc of sarcomeres. Mutations in the human MLP gene are associated with hypertrophic and dilated cardiomyopathy.", "Our data demonstrate that Mlp84B is essential for normal cardiac function and establish the Drosophila model for the investigation of the mechanisms connecting defective cardiac Z-disc components to the development of cardiomyopathy.", "Muscle LIM protein (MLP) is a cytoskeletal LIM-only protein expressed in striated muscle. Mutations in human MLP are associated with cardiomyopathy;", "TTN-encoded titin, CSRP3-encoded muscle LIM protein, and TCAP-encoded telethonin are Z-disc proteins essential for the structural organization of the cardiac sarcomere and the cardiomyocyte's stretch sensor. All three genes have been established as cardiomyopathy-associated genes for both dilated cardiomyopathy (DCM) and hypertrophic cardiomyopathy (HCM). ", "Approximately 4.1% of unrelated patients had HCM-associated MLP or TCAP mutations. MLP/TCAP-HCM phenotypically mirrors myofilament-HCM and is more severe than the subset of patients who still remain without a disease-causing mutation. The precise role of W4R-MLP in the pathogenesis of either DCM or HCM warrants further investigation.", "MLP (muscle-LIM-protein) deficient mice develop DCM and changes in the mechanical coupling of cardiomyocytes result in alterations at the intercalated disks and enhanced accumulation of adherens junction proteins.", "Targeted deletion of cytoskeletal muscle LIM protein (MLP) in mice consistently leads to dilated cardiomyopathy (DCM) after one or more months. ", "In summary, young MLPKO mice revealed substantial alterations in passive myocardial properties and relaxation time, but not in most systolic characteristics. These results indicate that the progression to heart failure in the MLPKO model may be driven by diastolic myocardial dysfunction and abnormal passive properties rather than systolic dysfunction.", "Mice lacking the muscle LIM protein (MLP) develop morphological and clinical signs resembling human dilated cardiomyopathy and heart failure.", "Our results show that the absence of MLP causes a local loss of mitochondria. We hypothesize that this is caused by a disturbed interaction between cytoskeleton and mitochondria, which interferes with energy sensing and energy transfer. Recovery of energy depletion by stimulating mitochondrial biogenesis might be a useful therapeutic strategy for improving the energy imbalance in heart failure.", "Previous work has shown that mutations in muscle LIM protein (MLP) can cause hypertrophic cardiomyopathy (HCM). In order to gain an insight into the molecular basis of the disease phenotype, we analysed the binding characteristics of wild-type MLP and of the (C58G) mutant MLP that causes hypertrophic cardiomyopathy.", "The molecular basis for HCM-causing mutations in the MLP gene might therefore be an alteration in the equilibrium of interactions of the ternary complex MLP-N-RAP-alpha-actinin.", "Muscle LIM protein (MLP) is a member of the cysteine-rich protein (CRP) family and has been implicated in both myogenesis and sarcomere assembly. In the latter role, it binds zyxin and alpha-actinin, both of which are involved in actin organization. An MLP-deficient mouse has been described; these mice develop dilated cardiomyopathy and heart failure.", "We identified a patient with DCM and EFE, having a mutation in MLP with the residue lysine 69 substituted by arginine (K69R). ", "MLP-knockout mice develop a marked cardiac hypertrophy reaction and dilated cardiomyopathy (DCM). MLP is therefore a candidate gene for heritable forms of hypertrophic cardiomyopathy (HCM) and DCM in humans.", "Family studies revealed cosegregation of clinically affected individuals with the respective mutations in MLP. CONCLUSION: Here, we present evidence that mutations in the CRP3/MLP gene can cause HCM.", "The skeletal muscle LIM protein 1 (SLIM1) is highly expressed in skeletal and cardiac muscle, and its expression is downregulated significantly in dilated human cardiomyopathy. ", "Targeted disruption of muscle LIM protein (MLP) has previously been shown to result in dilated cardiomyopathy with many of the clinical signs of heart failure, although the effects of MLP disruption on passive ventricular mechanics and myocyte architecture are not known.", "These results suggest that the disruption of the cytoskeletal protein MLP results in less compliant passive tissue and concomitant structural alterations in the three-dimensional myocyte architecture that may in part explain the ventricular dysfunction in the dilated heart.", " Mutations in cysteine and glycine-rich protein 3 (CSRP3), the gene encoding MLP, have been directly associated with human cardiomyopathies, whereas aberrant expression patterns are reported in human cardiac and skeletal muscle diseases.", "Muscle LIM protein (MLP) has been proposed to be a central player in the pathogenesis of heart muscle disease.", "Previous work has shown that mutations in muscle LIM protein (MLP) can cause hypertrophic cardiomyopathy (HCM)" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/16228909", "http://www.ncbi.nlm.nih.gov/pubmed/22421737", "http://www.ncbi.nlm.nih.gov/pubmed/15978612", "http://www.ncbi.nlm.nih.gov/pubmed/15639480", "http://www.ncbi.nlm.nih.gov/pubmed/11788418", "http://www.ncbi.nlm.nih.gov/pubmed/21562304", "http://www.ncbi.nlm.nih.gov/pubmed/21484537", "http://www.ncbi.nlm.nih.gov/pubmed/15205937", "http://www.ncbi.nlm.nih.gov/pubmed/18083727", "http://www.ncbi.nlm.nih.gov/pubmed/22371524", "http://www.ncbi.nlm.nih.gov/pubmed/14567970", "http://www.ncbi.nlm.nih.gov/pubmed/16352453", "http://www.ncbi.nlm.nih.gov/pubmed/12642359", "http://www.ncbi.nlm.nih.gov/pubmed/18505755", "http://www.ncbi.nlm.nih.gov/pubmed/12397030", "http://www.ncbi.nlm.nih.gov/pubmed/17535853", "http://www.ncbi.nlm.nih.gov/pubmed/24860983" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009202", "http://www.disease-ontology.org/api/metadata/DOID:0050700" ]

[ "The T790M mutation refers to the mutation in exon 20 of the EGFR gene" ]

[ "EGFR", "epidermal growth factor receptor" ]

[ "Nearly one half of all cases of acquired resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) for non-small-cell lung cancer (NSCLC) are due to the T790M mutation in EGFR exon 20. ", "Two types of epidermal growth factor receptor (EGFR) mutations in exon 19 and exon 21 (ex19del and L858R) are prevalent in lung cancer patients and sensitive to targeted EGFR inhibition. A resistance mutation in exon 20 (T790M) has been found to accompany drug treatment when patients relapse. ", "Acquired EGFR C797S mutation mediates resistance to AZD9291 in non-small cell lung cancer harboring EGFR T790M.", "However, resistance to the EGFR TKIs develops mostly secondary to T790M mutation in exon 20. ", "The T790M mutation in EGFR accounts for approximately half of all lung cancer cases with acquired resistance to the current clinical EGFR tyrosine kinase inhibitors.", "In nonsmall cell lung cancer (NSCLC), the threonine(790)-methionine(790) (T790M) point mutation of EGFR kinase is one of the leading causes of acquired resistance to the first generation tyrosine kinase inhibitors (TKIs), such as gefitinib and erlotinib", "Both AKT and MEK inhibition contributed to cell death independent of erlotinib in the T790M-containing H1975 and the EGFR-WT cell lines tested.", " The EGFR T790M mutation is generally considered to be the molecular genetic basis of acquired TKI resistance", "Prognostic impact of central nervous system metastases after acquired resistance to EGFR-TKI: poorer prognosis associated with T790M-negative status and leptomeningeal metastases.", "In EGFR-mutated NSCLC cell lines with the acquired resistance threonine-to-methionine mutation in codon 790 (T790M) mutation, ", "To overcome T790M-mediated acquired resistance of lung cancer cells to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs), second generation ", "Approximately 50% of cases of acquired resistance (AR) are due to a secondary T790M mutation in exon 20 of the EGFR gene;" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/25667490", "http://www.ncbi.nlm.nih.gov/pubmed/25384171", "http://www.ncbi.nlm.nih.gov/pubmed/26056478", "http://www.ncbi.nlm.nih.gov/pubmed/25682017", "http://www.ncbi.nlm.nih.gov/pubmed/25806347", "http://www.ncbi.nlm.nih.gov/pubmed/25483995", "http://www.ncbi.nlm.nih.gov/pubmed/25323938", "http://www.ncbi.nlm.nih.gov/pubmed/25939061", "http://www.ncbi.nlm.nih.gov/pubmed/26124670", "http://www.ncbi.nlm.nih.gov/pubmed/26058074", "http://www.ncbi.nlm.nih.gov/pubmed/26396685", "http://www.ncbi.nlm.nih.gov/pubmed/25382705" ]

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[ "Exogenous FGF-2 was shown to increase angiogenesis and myocardial perfusion, promote myocardial regeneration by activating the SDF-1α/CXCR4 axis, and thereby improve the cardiac function after myocardial infarction. Furthermore, prevascularization with basic FGF-incorporated microspheres enhances the benefits of cardiomyocyte transplantation. In another study, transmyocardial drilling revascularization combined with heparinized basic fibroblast growth factor (bFGF)-incorporating degradable stent implantation (TMDRSI) was shown to promote Cardiac Progenitor Cells proliferation and differentiation into cardiomyocytes through activating the SDF-1/CXCR4 axis, while inhibiting myocardial apoptosis, thereby enhancing myocardial regeneration following myocardial infarction and improving cardiac function." ]

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[ "To investigate whether transmyocardial drilling revascularization combined with heparinized basic fibroblast growth factor (bFGF)-incorporating degradable stent implantation (TMDRSI) can promote myocardial regeneration after acute myocardial infarction", "The new method has shown to be capable of promoting CSCs proliferation and differentiation into cardiomyocytes through activating the SDF-1/CXCR4 axis, while inhibiting myocardial apoptosis, thereby enhancing myocardial regeneration following AMI and improving cardiac function. This may provide a new strategy for myocardial regeneration following AMI.", "To investigate the effects of exogenous basic fibroblast growth factor (bFGF) on myocardial regeneration after acute myocardial infarction (AMI).", "Exogenous bFGF was shown to have increased angiogenesis and myocardial perfusion, promoted myocardial regeneration by activating the SDF-1α/CXCR4 axis, and thereby improved the cardiac function, which may provide a new therapeutic strategy for AMI.", "Support to the paracrine hypothesis is provided by data showing that several genes, coding for factors (VEGF, FGF-2, HGF, IGF-I, and TB4) that are potential mediators of the effects exerted by the Akt-MSC conditioned medium, are significantly up-regulated in the Akt-MSCs, particularly in response to hypoxia. Taken together, our data support Akt-MSC-mediated paracrine mechanisms of myocardial protection and functional improvement.", "Prevascularization with basic fibroblast growth factor-incorporated microspheres enhances the benefits of cardiomyocyte transplantation. We expect that this system will contribute to regeneration medicine through its extensive application to other growth factors." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/17693930", "http://www.ncbi.nlm.nih.gov/pubmed/22146760", "http://www.ncbi.nlm.nih.gov/pubmed/16581974", "http://www.ncbi.nlm.nih.gov/pubmed/21422919", "http://www.ncbi.nlm.nih.gov/pubmed/12580776", "http://www.ncbi.nlm.nih.gov/pubmed/12091808" ]

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[ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009203", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016222", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012038" ]

[ "Loss-of-function mutations of NSD1 and 5q35 microdeletions encompassing NSD1 are a major cause of Sotos syndrome (Sos), which is characterized by overgrowth, macrocephaly, characteristic facies, and variable intellectual disability (ID).", "Loss-of-function mutations of NSD1 and 5q35 microdeletions encompassing NSD1 are a major cause of Sotos syndrome (Sos), which is characterized by overgrowth, macrocephaly, characteristic facies, and variable intellectual disability (ID)" ]

[ "yes" ]

[ "Loss-of-function mutations of NSD1 and 5q35 microdeletions encompassing NSD1 are a major cause of Sotos syndrome (Sos), which is characterized by overgrowth, macrocephaly, characteristic facies, and variable intellectual disability (ID)", "We observed a novel 3.5 Mb 5q subtelomeric deletion in a 3-year-old girl with developmental delay, hypotonia and multiple minor anomalies. Comparison of her phenotype with the few published patients with terminal 5q35 deletions revealed several overlapping features, but also showed remarkable differences such as shortness of stature versus macrosomia. After the report of 5q35.3 microdeletions in Sotos syndrome we integrated the published BACs into the public draft sequence and exactly mapped the deletion size in our patient by FISH analysis with 15 BAC probes. We demonstrated that the deletion in our patient is immediately adjacent to the reported Sotos syndrome deletion site", "Switch in FGFR3 and -4 expression profile during human renal development may account for transient hypercalcemia in patients with Sotos syndrome due to 5q35 microdeletions.", "Multiple mechanisms are implicated in the generation of 5q35 microdeletions in Sotos syndrome.", "After the report of 5q35.3 microdeletions in Sotos syndrome we integrated the published BACs into the public draft sequence and exactly mapped the deletion size in our patient by FISH analysis with 15 BAC probes.", "Clinical and genetic spectrum of 18 unrelated Korean patients with Sotos syndrome: frequent 5q35 microdeletion and identification of four novel NSD1 mutations.", "Here we describe a new case of Sotos syndrome with a 5q35 microdeletion, affecting the fibroblast growth factor receptor 4 (FGFR4) gene, presenting with infantile hypercalcemia.", "Microdeletions at 5q35.3, encompassing NSD1, are responsible for approximately 10% of non-Japanese cases of Sotos.", "Alu-related 5q35 microdeletions in Sotos syndrome.", "Most cases of Sotos syndrome are caused by intragenic NSD1 mutations or 5q35 microdeletions.", "Multiple mechanisms are implicated in the generation of 5q35 microdeletions in Sotos syndrome", "Clinical and genetic spectrum of 18 unrelated Korean patients with Sotos syndrome: frequent 5q35 microdeletion and identification of four novel NSD1 mutations", "Microdeletions at 5q35.3, encompassing NSD1, are responsible for approximately 10% of non-Japanese cases of Sotos", "A case of Sotos syndrome with 5q35 microdeletion and novel clinical findings.", "Here we describe a new case of Sotos syndrome with a 5q35 microdeletion, affecting the fibroblast growth factor receptor 4 (FGFR4) gene, presenting with infantile hypercalcemia. ", "There are two types of mutations that cause NSD1 haploinsufficiency: mutations within the NSD1 gene (mutation type) and a 5q35 submicroscopic deletion encompassing the entire NSD1 gene (deletion type). ", "aCGH and metaphase FISH are useful for rapid diagnosis of 5q35 microdeletion associated with Sotos syndrome.", "Multiple mechanisms are implicated in the generation of 5q35 microdeletions in Sotos syndrome.", "Switch in FGFR3 and -4 expression profile during human renal development may account for transient hypercalcemia in patients with Sotos syndrome due to 5q35 microdeletions.", "A case of Sotos syndrome with 5q35 microdeletion and novel clinical findings.", "Most cases of Sotos syndrome are caused by intragenic NSD1 mutations or 5q35 microdeletions.", "aCGH and metaphase FISH are useful for rapid diagnosis of 5q35 microdeletion associated with Sotos syndrome.", "Alu-related 5q35 microdeletions in Sotos syndrome." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/25510705", "http://www.ncbi.nlm.nih.gov/pubmed/18505455", "http://www.ncbi.nlm.nih.gov/pubmed/12900893", "http://www.ncbi.nlm.nih.gov/pubmed/16140999", "http://www.ncbi.nlm.nih.gov/pubmed/23190751", "http://www.ncbi.nlm.nih.gov/pubmed/15805156", "http://www.ncbi.nlm.nih.gov/pubmed/24670087", "http://www.ncbi.nlm.nih.gov/pubmed/24192683", "http://www.ncbi.nlm.nih.gov/pubmed/22012791", "http://www.ncbi.nlm.nih.gov/pubmed/23913520" ]

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[ "Multiple endocrine neoplasia type 1 syndrome is an inherited cancer syndrome defined by occurrence of multiple neuro-endocrine tumors and is classically associated with the combined occurrence of two or more tumors involving parathyroid gland, pancreas and pituitary gland. Other tumors, including but not limited to adrenal cortical tumor, carcinoid tumors lipoma, leiomyoma, duodenal gastrinoma, hepatic focal nodular hyperplasia, and renal angiomyolipoma, angiofibroma, colagenoma, thyroid tumor and meningioma, may also be present." ]

[ "parathyroid gland", "pancreas", "pituitary gland" ]

[ "Multiple endocrine neoplasia type 1 (MEN1; formerly known as Wermer syndrome) is a rare disorder characterized by the combined occurrence of two or more tumors involving parathyroid, pancreatic islets and anterior pituitary glands; some other tumors have also been described.", " Hyperparathyroidism is the most common feature of MEN1 (95% of patients), pancreatic islet tumors or pancreatic NET (neuroendocrine tumor) occur in 40-70% and pituitary tumors in 30-40% of MEN 1 patients", " In addition, other tumors, such as adrenal cortical tumors, carcinoid tumors, lipomas, angiofibromas, colagenomas and meningiomas may be present. ", "the most important causes malignant pancreatic neuroendocrine tumors (NET) and thymic carcinoids. ", "Multiple endocrine neoplasia type 1 (MEN1) is inherited in an autosomal dominant fashion and predisposes to the development of hyperplastic or neoplastic changes in the parathyroid and pituitary glands and the endocrine pancreas, along with numerous other characteristic tumors and features. ", "Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disorder characterized by the combined occurrence of parathyroid and adrenocortical tumors, and neuroendocrine tumors (NETs) of the pancreas and pituitary. ", "The pancreatic NETs are predominantly gastrinomas and insulinomas, and the pituitary NETs are mostly prolactinomas and somatotrophinomas. ", "We address the potential role of miRNAs in the endocrine pancreas, the pituitary gland, and the parathyroid glands-areas where MEN 1 shows high penetrance. ", "Moreover, studies have provided evidence that dysregulation of miRNAs was responsible for endocrine carcinogenesis, including pancreatic, pituitary, and parathyroid tumors.", "MEN1 and MEN2 are rare inherited cancer syndromes which express a variety of endocrine and nonendocrine tumors.", "Multiple endocrine neoplasia Type 1 (MEN1) is a rare hereditary tumor syndrome predisposing to tumor development in several endocrine organs.", " Its major manifestations include hyperparathyroidism, tumors of endocrine pancreas and pituitary. ", "eside these three, several other endocrine (adrenocortical, foregut carcinoid) and nonendocrine (lipoma, angiofibroma, collagenoma, ependymoma, meningioma) tumors have been described to be associated with this syndrome", "Both familial and sporadic forms of the disease are known. The diagnosis of MEN1 can be established if two of the three major manifestations are found in the same patient, whereas the diagnosis of familial MEN1 requires one MEN1 patient and a first degree relative with at least one MEN1 manifestation. ", "Both benign (parathyroid, anterior pituitary) and malignant (gastrinoma, glucagonoma) lesions may develop in MEN1 patients", "Multiple endocrine neoplasia type 1 (MEN1) is a classic hereditary tumor syndrome characterized by a genetic predisposition to develop a variety of neuroendocrine neoplasias and hormone excess syndromes.", "Multiple endocrine neoplasia type 1 (MEN 1) is a familial syndrome characterized by parathyroid, enteropancreatic and pituitary tumors. ", "Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant inherited tumor syndrome characterized by the development of multiple endocrine tumors", "Multiple facial angiofibromas were observed in 28 (88%) of the patients with MEN1, with 16 patients (50%) having 5 or more. Angiofibromas were clinically and histologically identical to those in individuals with tuberous sclerosis. Collagenomas were observed in 23 patients (72%). Also observed were cafe au lait macules in 12 patients (38%), lipomas in 11 patients (34%), confetti-like hypopigmented macules in 2 patients (6%), and multiple gingival papules in 2 patients (6%)", "Multiple angiofibromas, collagenomas, lipomas, confetti-like hypopigmented macules and multiple gingival papules are cutaneous manifestations of MEN1 and should be looked for in both family members of patients with MEN1 and individuals with hyperparathyroidism of other MEN1-associated tumors. ", "Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant inherited disorder characterized by nodular proliferation of the parathyroid glands and tumors of the anterior pituitary gland, the endocrine pancreas, and the neuroendocrine cell system of the gut.", "We report here a genetic study of a female MEN1 patient with the association of nodular hyperplasia of two parathyroid glands, an insulinoma, multiple duodenal gastrinomas, a prolactinoma, and a gastric carcinoid.", "Multiple endocrine neoplasia type 1 (MEN1) is defined clinically by the combined occurrence of multiple tumors, typically of the parathyroid glands, pancreatic islet cells, and anterior pituitary gland.", "In support of previous findings in islet tumors, we found down-regulation of the cell-cycle regulator, p18, in both the pancreatic islet and pituitary adenomas, suggesting that reduced p18 levels may be important for Men1-related tumorigenesis in multiple tissues. Surprisingly, we identified increased p16 transcript in pancreatic islet and pituitary tumors. ", " The patient was studied and diagnosed with a multiple endocrine neoplasia type I (MEN I), familiar (mother with MEN I). A scintigraphic study with 99mTc-MIBI was performed in order to localize hyperfunctioning parathyroid glands because of biochemical diagnosis of primary hyperparathyroidism. ", "The tumor was removed and histologically confirmed as a carcinoid within a thymus in a MEN type I syndrome. ", "MEN I patients can benefit from the examination with this agent which can potentially localize not only parathyroid endocrine pathology but also unknown associated tumors.", "Pancreatic endocrine tumors occur sporadically and as part of the multiple endocrine neoplasia type 1 (MEN 1) and von Hippel-Lindau (VHL) syndromes. ", "We have analyzed 22 nonfamilial and 16 MEN 1-associated pancreatic endocrine tumors for loss of heterozygosity (LOH) at 3p, 11q13, and 18q. LOH at 3p was revealed in 45% and 36% of tumors from 31 patients with nonfamilial and MEN 1-associated disease, respectively.", "The data indicate involvement of tumor suppressor genes on 3p and 18q, in addition to the MEN1 gene at 11q13, in the tumorigenesis of both nonfamilial and MEN 1-associated pancreatic endocrine tumors.", "Multiple endocrine neoplasia type 1 (MEN1) is characterized by the development of endocrine tumors of the parathyroid and pituitary glands, pancreas, and duodenum. Less frequently occurring tumors associated with MEN1 include non-endocrine tumors such as lipomas and angiofibromas. ", "An increased incidence of thyroid neoplasms, leiomyomas, adrenal cortical hyperplasia, hepatic focal nodular hyperplasia, and renal angiomyolipoma has been noted in the MEN1 population. ", "A germline mutation of the MEN1 gene was detected, and deletions of the MEN1 gene were consistently detected in multiple neuroendocrine tumors involving the parathyroid glands and the pancreas and a hepatic neuroendocrine tumor metastasis, as predicted by Knudson's \"two hit\" hypothesis.", "Two hits of the MEN1 gene were also detected in esophageal leiomyoma tissue, suggesting that tumorigenesis was directly related to the patient's underlying MEN1.", " In contrast, follicular thyroid adenoma, papillary thyroid carcinoma, hepatic focal nodular hyperplasia, and adrenal cortical hyperplasia consistently showed retained heterozygosity of the MEN1 gene with flanking markers and an intragenic marker. Therefore, these tumors appear to develop along pathogenetic pathways that are different from classical MEN1-associated tumors.", "Twelve unrelated (German MEN1 families and their associated tumors (5 parathyroid tumors, 1 vipoma, 1 gastrinoma, 1 insulinoma) were characterized for MEN1 gene mutations by single-strand conformational variant (SSCV) analysis and DNA sequence analysis as well as for loss of heterozygosity on chromosome 11q13. ", "Multiple endocrine neoplasia type 1 (MEN1) consists of benign, and sometimes malignant, tumors (often multiple in a tissue) of the parathyroids, enteropancreatic neuroendocrine system, anterior pituitary, and other tissues. Skin angiofibromas and skin collagenomas are common. " ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/23279763", "http://www.ncbi.nlm.nih.gov/pubmed/10664520", "http://www.ncbi.nlm.nih.gov/pubmed/9820618", "http://www.ncbi.nlm.nih.gov/pubmed/17455252", "http://www.ncbi.nlm.nih.gov/pubmed/23024266", "http://www.ncbi.nlm.nih.gov/pubmed/18172277", "http://www.ncbi.nlm.nih.gov/pubmed/11914929", "http://www.ncbi.nlm.nih.gov/pubmed/20175448", "http://www.ncbi.nlm.nih.gov/pubmed/9236523", "http://www.ncbi.nlm.nih.gov/pubmed/10614532", "http://www.ncbi.nlm.nih.gov/pubmed/23435440", "http://www.ncbi.nlm.nih.gov/pubmed/21302639", "http://www.ncbi.nlm.nih.gov/pubmed/7962349", "http://www.ncbi.nlm.nih.gov/pubmed/21613051", "http://www.ncbi.nlm.nih.gov/pubmed/9735087", "http://www.ncbi.nlm.nih.gov/pubmed/10496602", "http://www.ncbi.nlm.nih.gov/pubmed/10502325" ]

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[ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009369", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D018761" ]

[ "Ataxin-3 is a ubiquitously expressed deubiqutinating enzyme with important functions in the proteasomal protein degradation pathway and regulation of transcription. The C-terminus of the ataxin-3 protein contains a polyglutamine (PolyQ) region that, when mutationally expanded to over 52 glutamines, causes the neurodegenerative disease spinocerebellar ataxia 3 (SCA3).", "Spinocerebellar ataxia type 3 (SCA3) is the most frequent inherited cerebellar ataxia in Europe, the US and Japan, leading to disability and death through motor complications. Although the affected protein ataxin-3 is found ubiquitously in the brain, grey matter atrophy is predominant in the cerebellum and the brainstem" ]

[ "Ataxin-3" ]

[ "Spinocerebellar ataxia type 3 (SCA3) is the most frequent inherited cerebellar ataxia in Europe, the US and Japan, leading to disability and death through motor complications. Although the affected protein ataxin-3 is found ubiquitously in the brain, grey matter atrophy is predominant in the cerebellum and the brainstem", "Spinocerebellar ataxia type 3 (SCA3) is an inherited spinocerebellar ataxia caused by the expansion of trinucleotide CAG repeats in the gene encoding ataxin-3", "Ataxin-3 is a ubiquitously expressed deubiqutinating enzyme with important functions in the proteasomal protein degradation pathway and regulation of transcription. The C-terminus of the ataxin-3 protein contains a polyglutamine (PolyQ) region that, when mutationally expanded to over 52 glutamines, causes the neurodegenerative disease spinocerebellar ataxia 3 (SCA3)", "Spinocerebellar ataxia type 3 is a neurodegenerative disorder caused by the expansion of the polyglutamine repeat region within the ataxin-3 protein.", "Spinocerebellar ataxia type 3 is caused by a polyglutamine expansion in the ataxin-3 protein, resulting in gain of toxic function of the mutant protein.", "Here, we provide insight into the mechanism by which ubiquitination directly enhances the activity of ataxin-3, a DUb implicated in protein quality control and the disease protein in the polyglutamine neurodegenerative disorder, Spinocerebellar Ataxia Type 3", "Ataxin-3, the disease protein in the neurodegenerative disorder Spinocerebellar Ataxia Type 3 or Machado Joseph disease, is a cysteine protease implicated in the ubiquitin proteasome pathway", "Ataxin-3 (AT3) is the protein that triggers the inherited neurodegenerative disorder spinocerebellar ataxia type 3 when its polyglutamine (polyQ) stretch close to the C-terminus exceeds a critical length", "Here, in studies of spinocerebellar ataxia type 3, also known as Machado-Joseph disease (SCA3/MJD), we show that the disease protein ataxin-3 accumulates in ubiquitinated intranuclear inclusions selectively in neurons of affected brain regions.", "This pathogenic repeat in MJD/SCA3 encodes an expanded tract of the amino acid glutamine in the disease protein, which is known as ataxin-3.", "Machado-Joseph disease (MJD), also called spinocerebellar ataxia type 3, is caused by mutant ataxin-3 with a polyglutamine expansion.", " Mutant ataxin-3 is aberrantly folded and proteolytically cleaved in spinocerebellar ataxia type 3. The C-terminal region of the protein includes a polyglutamine stretch that is expanded in spinocerebellar ataxia type 3.", "Spinocerebellar ataxia type 3 is a neurodegenerative disorder caused by the expansion of the polyglutamine repeat region within the ataxin-3 protein." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/20943656", "http://www.ncbi.nlm.nih.gov/pubmed/21827905", "http://www.ncbi.nlm.nih.gov/pubmed/24293103", "http://www.ncbi.nlm.nih.gov/pubmed/24272589", "http://www.ncbi.nlm.nih.gov/pubmed/9292723", "http://www.ncbi.nlm.nih.gov/pubmed/23659897", "http://www.ncbi.nlm.nih.gov/pubmed/20865150", "http://www.ncbi.nlm.nih.gov/pubmed/16389311", "http://www.ncbi.nlm.nih.gov/pubmed/21653538", "http://www.ncbi.nlm.nih.gov/pubmed/23617879", "http://www.ncbi.nlm.nih.gov/pubmed/20007218", "http://www.ncbi.nlm.nih.gov/pubmed/24685680" ]

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[ "The transposon mutagenesis and high-throughput sequencing (Tn-seq) is a technique that allows for quantitative assessment of individual mutants within a transposon mutant library by sequencing the transposon-genome junctions and then compiling mutant presence by mapping to a base genome. Using Tn-seq, it is possible to quickly define all the insertional mutants in a library and thus identify nonessential genes under the conditions in which the library was produced. Identification of fitness of individual mutants under specific conditions can be performed by exposing the library to selective pressures." ]

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[ " Using Tn-seq, a genome-wide fitness profiling technique, we identified several functions required for fitness of Y. pestis in vivo that were not previously known to be important.", "Tn-seq is a technique that allows for quantitative assessment of individual mutants within a transposon mutant library by sequencing the transposon-genome junctions and then compiling mutant presence by mapping to a base genome. Using Tn-seq, it is possible to quickly define all the insertional mutants in a library and thus identify nonessential genes under the conditions in which the library was produced. Identification of fitness of individual mutants under specific conditions can be performed by exposing the library to selective pressures.", "Genome-wide fitness and genetic interactions determined by Tn-seq, a high-throughput massively parallel sequencing method for microorganisms.", "Tn-seq: high-throughput parallel sequencing for fitness and genetic interaction studies in microorganisms.", "Here we present the method Tn-seq, with which it has become possible to quantitatively determine fitness for most genes in a microorganism and to screen for quantitative genetic interactions on a genome-wide scale and in a high-throughput fashion. Tn-seq can thus direct studies in the annotation of genes and untangle complex phenotypes. ", "Here we present a method (Tn-seq) for accurately determining quantitative genetic interactions on a genome-wide scale in microorganisms. Tn-seq is based on the assembly of a saturated Mariner transposon insertion library. After library selection, changes in frequency of each insertion mutant are determined by sequencing the flanking regions en masse. ", "Whole-genome fitness analysis in microbes that uses saturating transposon mutagenesis combined with massively parallel sequencing (Tn-seq) is providing a measure of the contribution of each gene to a given growth condition. ", "The procedure employs a new Tn-seq methodology based on the generation and amplification of single-strand circles carrying transposon junction sequences (the Tn-seq circle method),", "Here we present a method (Tn-seq) for accurately determining quantitative genetic interactions on a genome-wide scale in microorganisms. Tn-seq is based on the assembly of a saturated Mariner transposon insertion library.", "Here we present the method Tn-seq, with which it has become possible to quantitatively determine fitness for most genes in a microorganism and to screen for quantitative genetic interactions on a genome-wide scale and in a high-throughput fashion. Tn-seq can thus direct studies in the annotation of genes and untangle complex phenotypes.", "Tn-seq measures the frequency of actual members of a heterogeneous mutant pool undergoing purifying selection to determine the contribution of every non-essential gene in the genome to the fitness of an organism under a given condition. Here we use Tn-seq to assess gene function in the Gram negative γ-proteobacterium Shewanella oneidensis strain MR-1.", "Towards this goal, we utilized a quantitative genetic footprinting technique known as transposon insertion sequencing (Tn-seq) in conjunction with comparative pathogenomics to functionally dissect the genetic repertoire of a reference ExPEC isolate. Using Tn-seq and high-throughput zebrafish infection models, we tracked changes in the abundance of ExPEC variants within saturated transposon mutant libraries following selection within distinct host niches." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/21253457", "http://www.ncbi.nlm.nih.gov/pubmed/19767758", "http://www.ncbi.nlm.nih.gov/pubmed/25636611", "http://www.ncbi.nlm.nih.gov/pubmed/22925268", "http://www.ncbi.nlm.nih.gov/pubmed/24077707", "http://www.ncbi.nlm.nih.gov/pubmed/25139902", "http://www.ncbi.nlm.nih.gov/pubmed/23990803", "http://www.ncbi.nlm.nih.gov/pubmed/21053251" ]

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[ "The metabolic syndrome (MetS) is characterized by a cluster of risk factors including central obesity, hypertension, dyslipidemia and insulin resistance, The MetS is associated with an increased risk for cardiovascular disease (CVD) and type 2 diabetes mellitus (T2DM)." ]

[ "yes" ]

[ "The metabolic syndrome (MetS) is characterized by a cluster of risk factors including central obesity, hypertension, dyslipidemia and insulin resistance, The MetS is associated with an increased risk for cardiovascular disease (CVD) and type 2 diabetes mellitus (T2DM). ", "As a molecular link between metabolic signals, inflammation, and vascular dysfunction, resistin can be proposed as playing a significant role in the heightened inflammatory state induced by metabolic stress linked to excessive caloric intake, thus contributing to the risk for metabolic syndrome (MetS), type 2 diabetes (T2DM), and cardiovascular disease (CVD). ", "The metabolic syndrome (MetS) is associated with a higher risk for both, type 2 diabetes mellitus and cardiovascular disease. ", "arotid intima-media thickness (CIMT) has been widely used as a surrogate marker of atherosclerosis and cardiovascular disease (CVD)" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/18945929", "http://www.ncbi.nlm.nih.gov/pubmed/24247648", "http://www.ncbi.nlm.nih.gov/pubmed/19196885", "http://www.ncbi.nlm.nih.gov/pubmed/24320036", "http://www.ncbi.nlm.nih.gov/pubmed/24320031", "http://www.ncbi.nlm.nih.gov/pubmed/24287796", "http://www.ncbi.nlm.nih.gov/pubmed/24328010", "http://www.ncbi.nlm.nih.gov/pubmed/21234418", "http://www.ncbi.nlm.nih.gov/pubmed/24320038", "http://www.ncbi.nlm.nih.gov/pubmed/24290090" ]

[ { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A2041867", "o": "Syndrome, Metabolic Cardiovascular" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A2029581", "o": "Cardiovascular Syndrome, Metabolic" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A2029582", "o": "Cardiovascular Syndromes, Metabolic" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A17989670", "o": "Metabolic Cardiovascular Syndrome" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A2035905", "o": "Metabolic Cardiovascular Syndrome" } ]

[ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D024821", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D002318", "http://www.disease-ontology.org/api/metadata/DOID:14221", "http://www.disease-ontology.org/api/metadata/DOID:1287" ]

[ "Several labs have obtained evidence for a protein complex that involves many of the nonstructural (NS) proteins encoded by the virus. NS3, NS4A, NS4B, NS5A, and NS5B appear to interact structurally and functionally. The interaction between the helicase, NS3, and the RNA polymerase, NS5B play a key role in viral replication. Pull-down experiments and surface plasmon resonance data indicate a direct interaction between NS3 and NS5B that is primarily mediated through the protease domain of NS3. This interaction reduces the basal ATPase activity of NS3. However, NS5B stimulates product formation in RNA unwinding experiments under conditions of excess nucleic acid substrate. When the concentrations of NS3 and NS5B are in excess of nucleic acid substrate, NS5B reduces the rate of NS3-catalyzed unwinding. Under pre-steady-state conditions, in which NS3 and substrate concentrations are similar, product formation increased in the presence of NS5B. The increase was consistent with 1:1 complex formed between the two proteins." ]

[ "yes" ]

[ "Several labs have obtained evidence for a protein complex that involves many of the nonstructural (NS) proteins encoded by the virus. NS3, NS4A, NS4B, NS5A, and NS5B appear to interact structurally and functionally. In this study, we investigated the interaction between the helicase, NS3, and the RNA polymerase, NS5B. Pull-down experiments and surface plasmon resonance data indicate a direct interaction between NS3 and NS5B that is primarily mediated through the protease domain of NS3. This interaction reduces the basal ATPase activity of NS3. However, NS5B stimulates product formation in RNA unwinding experiments under conditions of excess nucleic acid substrate. When the concentrations of NS3 and NS5B are in excess of nucleic acid substrate, NS5B reduces the rate of NS3-catalyzed unwinding. Under pre-steady-state conditions, in which NS3 and substrate concentrations are similar, product formation increased in the presence of NS5B. The increase was consistent with 1:1 complex formed between the two proteins. A fluorescently labeled form of NS3 was used to investigate this interaction through fluorescence polarization binding assays. Results from this assay support interactions that include a 1:1 complex formed between NS3 and NS5B.", "Contradictory results have been reported regarding NS3 in RNA synthesis. To investigate the effect of NS3 on classical swine fever virus (CSFV) NS5B RNA-dependent RNA polymerase activity (RdRp) activity and NS3-NS5B interaction, RdRp reactions, GST-pull-down assays and co-immunoprecipitation analyses containing NS5B and either of NS3 protein and the different truncated NS3 mutants were performed, respectively. We found that NS3 stimulated NS5B RdRp activity in a dose-dependent manner by binding to NS5 through a NS3 protease domain. Furthermore, mapping important regions of the NS3 protease domain was carried out by deletion mutagenesis, associated with RdRp reactions, GST-pull-down assays and co-immunoprecipitation analyses. Results showed that stimulation of CSFV NS5B RdRp activity was obtained by NS3 binding to NS5B through a 31-amino acid fragment at the N-terminal end of NS3 protease domain, which mediated a specific NS3-NS5B interaction.", "The protocols detailed in this unit are used to purify three recombinant enzymes that are widely used in HCV research: the HCV NS3 protease domain, the helicase domain as an NS3+NS4A complex, and the NS5B RNA-dependent RNA polymerase. The active enzymes are purified to homogeneity by two-column chromatography to support a screening program for HCV inhibitors.", "Among potential targets are viral entry factors, including scavenger receptor type B1 (SR-B1) and CD81, as well as neutralizing antibodies against the viral glycoproteins. Popular targets related to translation and replication are the NS3/4A protease (inhibited by telaprevir and boceprevir) and the NS5B polymerase, as well as the NS2/3 autoprotease, the NS3 helicase, and nonenzymatic targets such as NS4B and NS5A proteins. ", "The NS3 helicase domain competes with NS3 full-length for NS5 RdRp binding, with a K(d.) of 2.5μM. Since NS3 and NS5 are required for DENV replication, this fascile assay could be used to screen for non-nucleoside, allosteric inhibitors that disrupt the interaction between the two proteins." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/23463199", "http://www.ncbi.nlm.nih.gov/pubmed/22040846", "http://www.ncbi.nlm.nih.gov/pubmed/17319152", "http://www.ncbi.nlm.nih.gov/pubmed/19951725", "http://www.ncbi.nlm.nih.gov/pubmed/21946389", "http://www.ncbi.nlm.nih.gov/pubmed/23157297", "http://www.ncbi.nlm.nih.gov/pubmed/17660525", "http://www.ncbi.nlm.nih.gov/pubmed/21898331", "http://www.ncbi.nlm.nih.gov/pubmed/15917225", "http://www.ncbi.nlm.nih.gov/pubmed/18179252" ]

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[ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D018067", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012194", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D020365", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012324", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012367" ]

[ "Yes. The breast cancer-associated BRCA1 and BRCA2 proteins are strongly implicated in recombination repair.", "Carcinogenesis or oncogenesis or tumorigenesis is literally the creation of cancer. It is a process by which normal cells are transformed into cancer cells. It is characterized by a progression of changes at the cellular, genetic and epigenetic level that ultimately reprogram a cell to undergo uncontrolled cell division, thus forming a malignant mass.\nCarcinogenesis is caused by mutation and epimutation of the genetic material of normal cells, which upsets the normal balance between proliferation and cell death. This results in uncontrolled cell division and the evolution of those cells by natural selection in the body. The uncontrolled and often rapid proliferation of cells can lead to benign tumors; some types of these may turn into malignant tumors (cancer). Based on studies, carcinogenesis also related with the defects in recombination repair." ]

[ "yes" ]

[ "Inherited mutations in genes involved in HR are associated with gene rearrangement and may be a prerequisite for tumor development in some cancer-prone hereditary diseases like Bloom, Werner and Rothmund-Thomson syndromes. ", "Variants in the XRCC3 gene might result in altered protein structure or function which may influence DSBR efficiency and lead to cancer. ", "Although alcohol consumption is related to increased cancer risk, its molecular mechanism remains unclear. Here, we demonstrate that an intake of 10% alcohol for 4 weeks in rats is genotoxic due to induction of micronuclei. Acetaldehyde (AA), the first product of ethanol metabolism, is believed to be responsible for DNA damage induced by alcohol. ", "Although efficiency of these repair processes substantially decrease the efficacy of cancer chemotherapies that target DNA, compromised DNA repair contributes to mutagenesis and genomic instability leading to carcinogenesis.", "damage response and repair pathways are important barriers to carcinogenesis. ", "olymorphisms in DNA repair genes and differences in repair capacity between individuals have been widely documented. For colorectal cancer, the loss of mismatch repair gene activity is a key genetic determinant. Nucleotide excision repair (NER), recombination repair (RR) and base excision repair (BER) pathways have critical roles in protection against other cancers, and we wished to investigate their role in colorectal cancer. " ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/22276468", "http://www.ncbi.nlm.nih.gov/pubmed/11178982", "http://www.ncbi.nlm.nih.gov/pubmed/12592385", "http://www.ncbi.nlm.nih.gov/pubmed/21404276", "http://www.ncbi.nlm.nih.gov/pubmed/24051048", "http://www.ncbi.nlm.nih.gov/pubmed/23721719", "http://www.ncbi.nlm.nih.gov/pubmed/19083132", "http://www.ncbi.nlm.nih.gov/pubmed/17397816", "http://www.ncbi.nlm.nih.gov/pubmed/24104500", "http://www.ncbi.nlm.nih.gov/pubmed/12865926", "http://www.ncbi.nlm.nih.gov/pubmed/12016139", "http://www.ncbi.nlm.nih.gov/pubmed/23541693", "http://www.ncbi.nlm.nih.gov/pubmed/17636314", "http://www.ncbi.nlm.nih.gov/pubmed/12427531", "http://www.ncbi.nlm.nih.gov/pubmed/12488587", "http://www.ncbi.nlm.nih.gov/pubmed/22798379", "http://www.ncbi.nlm.nih.gov/pubmed/21267443", "http://www.ncbi.nlm.nih.gov/pubmed/17363343", "http://www.ncbi.nlm.nih.gov/pubmed/22665067", "http://www.ncbi.nlm.nih.gov/pubmed/23675572", "http://www.ncbi.nlm.nih.gov/pubmed/23125219", "http://www.ncbi.nlm.nih.gov/pubmed/20298636", "http://www.ncbi.nlm.nih.gov/pubmed/10753787", "http://www.ncbi.nlm.nih.gov/pubmed/16258176", "http://www.ncbi.nlm.nih.gov/pubmed/23620081", "http://www.ncbi.nlm.nih.gov/pubmed/11395777", "http://www.ncbi.nlm.nih.gov/pubmed/23628323", "http://www.ncbi.nlm.nih.gov/pubmed/16555998", "http://www.ncbi.nlm.nih.gov/pubmed/12191483", "http://www.ncbi.nlm.nih.gov/pubmed/15660524", "http://www.ncbi.nlm.nih.gov/pubmed/21427292" ]

[ { "p": "http://purl.uniprot.org/core/title", "s": "http://purl.uniprot.org/pubmed/9111189", "o": "Which DNA polymerases are used for DNA-repair in eukaryotes?" }, { "p": "http://purl.uniprot.org/core/name", "s": "http://purl.uniprot.org/pubmed/9111189", "o": "Carcinogenesis" }, { "p": "http://www.w3.org/2004/02/skos/core#exactMatch", "s": "http://purl.uniprot.org/pubmed/9111189", "o": "http://purl.uniprot.org/pubmed/9111189" }, { "p": "http://purl.uniprot.org/core/title", "s": "http://purl.uniprot.org/pubmed/11062157", "o": "Identification of single nucleotide polymorphisms in human DNA repair genes." }, { "p": "http://purl.uniprot.org/core/name", "s": "http://purl.uniprot.org/pubmed/11062157", "o": "Carcinogenesis" }, { "p": "http://www.w3.org/2004/02/skos/core#exactMatch", "s": "http://purl.uniprot.org/pubmed/11062157", "o": "http://purl.uniprot.org/pubmed/11062157" }, { "p": "http://purl.uniprot.org/core/title", "s": "http://purl.uniprot.org/pubmed/12419828", "o": "Diet, cancer and aging in DNA mismatch repair deficient mice." }, { "p": "http://www.w3.org/2004/02/skos/core#exactMatch", "s": "http://purl.uniprot.org/pubmed/12419828", "o": "http://purl.uniprot.org/pubmed/12419828" }, { "p": "http://purl.uniprot.org/core/name", "s": "http://purl.uniprot.org/pubmed/12419828", "o": "Carcinogenesis" }, { "p": "http://purl.uniprot.org/core/citation", "s": "http://purl.uniprot.org/uniprot/P18887", "o": "http://purl.uniprot.org/citations/10783319" }, { "p": "http://purl.uniprot.org/core/name", "s": "http://purl.uniprot.org/pubmed/10783319", "o": "Carcinogenesis" }, { "p": "http://www.w3.org/2004/02/skos/core#exactMatch", "s": "http://purl.uniprot.org/pubmed/10783319", "o": "http://purl.uniprot.org/medline/20247096" }, { "p": "http://www.w3.org/2004/02/skos/core#exactMatch", "s": "http://purl.uniprot.org/pubmed/10783319", "o": "http://purl.uniprot.org/pubmed/10783319" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_5031383838370036", "o": "X-ray repair cross-complementing protein 1" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_5031383838370035", "o": "DNA repair protein XRCC1" }, { "p": "http://www.w3.org/2004/02/skos/core#exactMatch", "s": "http://purl.uniprot.org/citations/10783319", "o": "http://purl.uniprot.org/pubmed/10783319" }, { "p": "http://purl.uniprot.org/core/title", "s": "http://purl.uniprot.org/pubmed/10590213", "o": "Involvement of p53 in X-ray induced intrachromosomal recombination in mice." }, { "p": "http://www.w3.org/2004/02/skos/core#exactMatch", "s": "http://purl.uniprot.org/pubmed/10590213", "o": "http://purl.uniprot.org/pubmed/10590213" }, { "p": "http://purl.uniprot.org/core/name", "s": "http://purl.uniprot.org/pubmed/10590213", "o": "Carcinogenesis" } ]

[ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004260", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005785", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0006281", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D059767", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D059765", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0006310", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0036298", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D063646", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011995", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0000724", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0000725", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D051721" ]

[ "Prevalence of Cystic Fibrosis varies according to the population. A theoretical estimate of the prevalence of cystic fibrosis based on anthropological data suggested a frequency of 25 affected individuals/100,000 inhabitants. However, real data indicated that the true prevalence in the population was considerably lower (6.9 cases/100,000 inhabitants). Results of literature reviews, surveys, and registry analyses revealed a mean prevalence of 0.737/10,000 in the 27 EU countries, which is similar to the value of 0.797 in the United States, and only one outlier, namely the Republic of Ireland at 2.98.", "The results of literature reviews, surveys, and registry analyses revealed a mean prevalence of 0.737/10,000 in the 27 EU countries, which is similar to the value of 0.797 in the United States, and only one outlier, namely the Republic of Ireland at 2.98 (PMID: 18442953) The allelic frequency of this variant was calculated to be 0.7% for this population (PMID: 22627569) CF mutations were identified in 374 (4.0%) individuals. (PMID: 11336401)" ]

[ "0.7–7/100000 inhabitants" ]

[ "The allelic frequency of this variant was calculated to be 0.7% for this population", "The results of literature reviews, surveys, and registry analyses revealed a mean prevalence of 0.737/10,000 in the 27 EU countries, which is similar to the value of 0.797 in the United States, and only one outlier, namely the Republic of Ireland at 2.98", "The age related prevalence of CF among the South Asian and general populations was: 0-14 years, 1:9200 versus 1:6600; 15-24 years, 1:13,200 versus 1:7600; older than 25 years, 1:56,600 versus 1:12,400.", "A theoretical estimate of the prevalence of cystic fibrosis based on anthropological data suggested a frequency of 25 affected individuals/100,000 inhabitants. However, our data indicated that the true prevalence in the population was considerably lower (6.9 cases/100,000 inhabitants)", "CF mutations were identified in 374 (4.0%) individuals.", "The aim of this study was to evaluate the screening policies of cystic fibrosis (CF) in the Jewish population." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/15970608", "http://www.ncbi.nlm.nih.gov/pubmed/11336401", "http://www.ncbi.nlm.nih.gov/pubmed/18442953", "http://www.ncbi.nlm.nih.gov/pubmed/15266396", "http://www.ncbi.nlm.nih.gov/pubmed/22627569", "http://www.ncbi.nlm.nih.gov/pubmed/18243066" ]

[]

[ "http://www.uniprot.org/uniprot/CFTR_MACMU", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D003550", "http://www.disease-ontology.org/api/metadata/DOID:2975", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005355", "http://www.disease-ontology.org/api/metadata/DOID:1485", "http://www.disease-ontology.org/api/metadata/DOID:10353", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D015995" ]

[ "Incontinentia pigmenti is an X-linked dominant disorder resulting from a mutation of IKBKG. This disorder has a classic dermatologic presentation, but neurologic involvement, with seizures and cortical infarction, can arise shortly after birth." ]

[ "yes" ]

[ "High-dose glucocorticoid therapy in the management of seizures in neonatal incontinentia pigmenti", "Incontinentia pigmenti is an X-linked dominant disorder resulting from a mutation of IKBKG. This disorder has a classic dermatologic presentation, but neurologic involvement, with seizures and cortical infarction, can arise shortly after birth", "Some children with incontinentia pigmenti exhibit encephalopathic features with severe seizures and disturbed consciousness, from the neonatal through the early infantile period", "Incontinentia pigmenti (IP) is a rare X-linked dominant neurocutaneous disorder affecting ectodermal tissue: skin, eyes, central nervous system, hair, nails, and teeth. It is usually lethal for males in utero. The involved gene is NEMO, an essential component of the nuclear factor-kappa B (NF-κB) signaling pathway. Skin lesions are highly diagnostic, occurring in neonates, with a particular distribution on Blaschko lines. The severity of the disease is related to ocular and neurological impairment. The hallmark of ocular IP is retinal vasculopathy including peripheral retinal vascular nonperfusion, macular infarction and neovascularization, and preretinal neovascularization. CNS involvement consists of seizures, mental retardation, hemiparesis, spasticity, microcephaly, cerebellar ataxia, and coma", "Incontinentia Pigmenti is a rare X-linked multisystem disorder with well described and pathognomonic skin manifestations. Neurological manifestations are found in 30% of IP patients, forming one of the major causes of morbidity and mortality of the condition. In this review, clinical and brain imaging data of 45 IP patients with a neurological phenotype are reviewed. Several clinical presentations could be identified, comprising seizures, infantile encephalopathy, acute disseminated encephalomyelitis and ischemic stroke", "Incontinentia pigmenti presenting as seizures.", "Neonatal seizures in two sisters with incontinentia pigmenti.", "High-dose glucocorticoid therapy in the management of seizures in neonatal incontinentia pigmenti: a case report.", "Incontinentia Pigmenti is an X-linked dominant neurocutaneous disorder with central nervous system manifestations in 30% of cases, including seizures and mental retardation.", "Neonatal seizures in two sisters with incontinentia pigmenti", "A rare cause of neonatal seizure: incontinentia pigmenti.", "Here, we describe the clinical, electrographic, and neuroradiologic effect of systemic glucocorticoid therapy in a neonate with incontinentia pigmenti manifesting an epileptic encephalopathy.", "Incontinentia pigmenti presenting as seizures.", "Neonatal seizures in two sisters with incontinentia pigmenti." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/22564885", "http://www.ncbi.nlm.nih.gov/pubmed/15127315", "http://www.ncbi.nlm.nih.gov/pubmed/24682289", "http://www.ncbi.nlm.nih.gov/pubmed/23622185", "http://www.ncbi.nlm.nih.gov/pubmed/12437562", "http://www.ncbi.nlm.nih.gov/pubmed/13679126", "http://www.ncbi.nlm.nih.gov/pubmed/25238668", "http://www.ncbi.nlm.nih.gov/pubmed/17990592" ]

[]

[]

[ "Hedgehog (Hh) signaling proteins stimulate cell proliferation, differentiation, and tissue patterning at multiple points in animal development. A single Hh homolog is present in Drosophila, but three Hh homologs, Sonic hedgehog (Shh), Indian hedgehog (Ihh) , and Desert hedgehog (Dhh), are present in mammals." ]

[ "Sonic hedgehog", "SHH", "Indian hedgehog", "IHH", "Desert hedgehog", "DHH" ]

[ "Hedgehog (Hh) signaling proteins stimulate cell proliferation, differentiation, and tissue patterning at multiple points in animal development. A single Hh homolog is present in Drosophila, but three Hh homologs, Sonic Hh, Indian Hh, and Desert Hh, are present in mammals.", " We report here biochemical and x-ray structural studies of Sonic, Indian, and Desert Hh proteins both alone and complexed with active domains of CDO and BOC.", "Previous work has shown that activin, a TGF(beta+) signaling molecule, permits pancreas development by repressing expression of Sonic hedgehog (Shh), a member of the hedgehog family of signaling molecules that antagonize pancreas development. Here we show that Indian hedgehog (Ihh), another hedgehog family member, and Patched 1 (Ptc1), a receptor and negative regulator of hedgehog activity, are expressed in pancreatic tissue.", "The original hedgehog (hh) gene was found in Drosophila and named for the appearance of a mutant phenotype which causes an embryo to be covered with pointy denticles, thus resembling a hedgehog. The hedgehog family consists of sonic hedgehog (Shh), desert hedgehog (Dhh), and Indian hedgehog (Ihh). ", "Indian hedgehog (IHH) is a secreted signaling molecule of the hedgehog family known to play important roles in the regulation of chondrocyte differentiation, cortical bone formation, and the development of joints.", "Hedgehog (Hh) plays a pivotal role in various tissues during embryonic development, tissue homeostasis and tumorigenesis. In mammals, Hh exists in three homologs: Desert hedgehog (Dhh), Indian hedgehog (Ihh) and Sonic hedgehog (Shh).", "Sonic hedgehog (SHH), Desert hedgehog (DHH) and Indian hedgehog (IHH) bind to Patched family receptors (PTCH1 and PTCH2) to transduce signals to GLI1, GLI2 and GLI3. GLI family transcription factors then activate transcription of Hedgehog target genes, such as FOXE1 and FOXM1 encoding Forkhead-box transcription factors.", "Indian hedgehog (IHH) and its receptors patched (PTC) and smoothened (SMO) belong to the hedgehog family of signaling molecules, which are essential for a variety of patterning events during mammalian tIssue development.", "In mammals, Hh exists in three homologs: Desert hedgehog (Dhh), Indian hedgehog (Ihh) and Sonic hedgehog (Shh).", "In mammals, Hh exists in three homologs: Desert hedgehog (Dhh), Indian hedgehog (Ihh) and Sonic hedgehog (Shh).", "A single Hh homolog is present in Drosophila, but three Hh homologs, Sonic Hh, Indian Hh, and Desert Hh, are present in mammals.", "A single Hh homolog is present in Drosophila, but three Hh homologs, Sonic Hh, Indian Hh, and Desert Hh, are present in mammals", "In mammals, Hh exists in three homologs: Desert hedgehog (Dhh), Indian hedgehog (Ihh) and Sonic hedgehog (Shh)" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/20519495", "http://www.ncbi.nlm.nih.gov/pubmed/22391297", "http://www.ncbi.nlm.nih.gov/pubmed/21167467", "http://www.ncbi.nlm.nih.gov/pubmed/12967338", "http://www.ncbi.nlm.nih.gov/pubmed/15645142", "http://www.ncbi.nlm.nih.gov/pubmed/18612197", "http://www.ncbi.nlm.nih.gov/pubmed/11044404" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D053823", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0097108", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005190" ]

[ "mTOR stands for: mammalian target of rapamycin." ]

[ "mammalian target of rapamycin" ]

[ " mammalian target of rapamycin (mTOR)", "mammalian target of rapamycin (mTOR)", "mammalian target of rapamycin (mTOR)", "mammalian target or rapamycin (mTOR)", "mammalian target of rapamycin (mTOR)", "mammalian target of rapamycin (mTOR) ", " mammalian target of rapamycin (mTOR)", " mammal target of rapamycin (mTOR)", " mammalian target of rapamycin (mTOR)", "mammalian Target of Rapamycin (mTOR)", " mammalian target of rapamycin (mTOR) " ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/24311635", "http://www.ncbi.nlm.nih.gov/pubmed/24309100", "http://www.ncbi.nlm.nih.gov/pubmed/24276258", "http://www.ncbi.nlm.nih.gov/pubmed/24290217", "http://www.ncbi.nlm.nih.gov/pubmed/24312355", "http://www.ncbi.nlm.nih.gov/pubmed/24307346", "http://www.ncbi.nlm.nih.gov/pubmed/24312415", "http://www.ncbi.nlm.nih.gov/pubmed/24289602", "http://www.ncbi.nlm.nih.gov/pubmed/24287118", "http://www.ncbi.nlm.nih.gov/pubmed/24270265", "http://www.ncbi.nlm.nih.gov/pubmed/24295418" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D058570", "http://www.uniprot.org/uniprot/MTOR_RAT" ]

[ "Joubert syndrome (JBTS) is an inherited ciliopathy giving rise to NPHP with cerebellar vermis aplasia and retinal degeneration. Among patients with JBTS and a cerebello-oculo-renal phenotype, mutations in CEP290 (NPHP6) are the most common genetic lesion.", "Nephronophthisis (NPHP) is the major cause of pediatric renal failure, yet the disease remains poorly understood, partly due to the lack of appropriate animal models. Joubert syndrome (JBTS) is an inherited ciliopathy giving rise to NPHP with cerebellar vermis aplasia and retinal degeneration. Among patients with JBTS and a cerebello-oculo-renal phenotype, mutations in CEP290 (NPHP6) are the most common genetic lesion" ]

[]

[ "Nephronophthisis (NPHP) is the major cause of pediatric renal failure, yet the disease remains poorly understood, partly due to the lack of appropriate animal models. Joubert syndrome (JBTS) is an inherited ciliopathy giving rise to NPHP with cerebellar vermis aplasia and retinal degeneration. Among patients with JBTS and a cerebello-oculo-renal phenotype, mutations in CEP290 (NPHP6) are the most common genetic lesion", "Among patients with JBTS and a cerebello-oculo-renal phenotype, mutations in CEP290 (NPHP6) are the most common genetic lesion.", "Among patients with JBTS and a cerebello-oculo-renal phenotype, mutations in CEP290 (NPHP6) are the most common genetic lesion", "Among patients with JBTS and a cerebello-oculo-renal phenotype, mutations in CEP290 (NPHP6) are the most common genetic lesion. ", "Joubert syndrome (JBTS) is an inherited ciliopathy giving rise to NPHP with cerebellar vermis aplasia and retinal degeneration. Among patients with JBTS and a cerebello-oculo-renal phenotype, mutations in CEP290 (NPHP6) are the most common genetic lesion.", "Among patients with JBTS and a cerebello-oculo-renal phenotype, mutations in CEP290 (NPHP6) are the most common genetic lesion. We present a Cep290 gene trap mouse model of JBTS that displays the kidney, eye, and brain abnormalities that define the syndrome.", "Among patients with JBTS and a cerebello-oculo-renal phenotype, mutations in CEP290 (NPHP6) are the most common genetic lesion." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/24946806" ]

[]

[]

[ "Patient Health Questionnaire-2 (PHQ-2) and Patient Health Questionnaire-9 (PHQ-9) are recommended by the American Heart Association for depression screening in cardiovascular patients." ]

[ "patient health questionnaire-2", "patient health questionnaire-9" ]

[ "In 2008, the American Heart Association (AHA) recommended a 2-step screening method, consisting of the 2-item Patient Health Questionnaire (PHQ-2) followed by the 9-item Patient Health Questionnaire (PHQ-9), for identifying depression in cardiovascular patients.", "The American Heart Association (AHA) statement has recommended routine screening for depression in coronary artery disease with a 2-stage implementation of the Patient Health Questionnaire (PHQ).", "A recent American Heart Association (AHA) Prevention Committee report recommended depression screening of all coronary heart disease patients using 2- and 9-item instruments from the Patient Health Questionnaire (PHQ-2 and PHQ-9) to identify patients who may need further assessment and treatment.", "Patients were screened for depression using a protocol identical to the one endorsed by the AHA in a cardiology community clinic in Elmhurst (Queens, New York). Depression was assessed using the Patient Health Questionnaire.", "Depression screening in cardiac patients has been recommended by the American Heart Association, but the best approach remains unclear. OBJECTIVE: To evaluate nurse-administered versions of the Patient Health Questionnaire for depression screening in patients hospitalized for acute coronary syndrome. METHODS: Staff nurses in an urban cardiac care unit administered versions 2, 9, and 10 of the questionnaire to 100 patients with acute coronary syndrome." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/23283084", "http://www.ncbi.nlm.nih.gov/pubmed/19840561", "http://www.ncbi.nlm.nih.gov/pubmed/18824640", "http://www.ncbi.nlm.nih.gov/pubmed/21862720", "http://www.ncbi.nlm.nih.gov/pubmed/20435186", "http://www.ncbi.nlm.nih.gov/pubmed/19261139", "http://www.ncbi.nlm.nih.gov/pubmed/21505152" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D003863", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D000572", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D008403" ]

[ "Genome-wide analysis of fragile sites by chromatin immunoprecipitation (ChIP) and microarray (ChIP-chip) of phosphorylated H2A in these mutants supported a transcription-dependent mechanism of DNA damage characteristic of R loops. Here we show that recombination factors are required for the survival of yeast FACT mutants, consistent with an accumulation of DNA breaks that we detected by Rad52 foci and transcription-dependent hyperrecombination. The latter pathway operates on nascent transcripts that are not simultaneously translated and requires factors Rho, NusG, and NusA, each of which is essential for viability of WT Escherichia coli. DNA replication in Escherichia coli is normally initiated at a single origin, oriC, dependent on initiation protein DnaA.", "Genome-wide analysis of fragile sites by chromatin immunoprecipitation (ChIP) and microarray (ChIP-chip) of phosphorylated H2A in these mutants supported a transcription-dependent mechanism of DNA damage characteristic of R loops\nA bisulfite-sensitivity assay may demonstrate genome-wide increase in the occurrence of RNA-DNA hybrids (R-loops)." ]

[ "yes" ]

[ "Genome-wide analysis of fragile sites by chromatin immunoprecipitation (ChIP) and microarray (ChIP-chip) of phosphorylated H2A in these mutants supported a transcription-dependent mechanism of DNA damage characteristic of R loops", "We have used a bisulfite-sensitivity assay to demonstrate genome-wide increase in the occurrence of RNA-DNA hybrids (R-loops), including from antisense and read-through transcripts, in a nusG missense mutant defective for Rho-dependent termination.", "The results demonstrate a key function of FACT in the resolution of R-loop-mediated transcription-replication conflicts, likely associated with a specific chromatin organization.", "Previous work revealed that GC skew and R-loop formation associate with a core set of unmethylated CpG island (CGI) promoters in the human genome" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/24164596", "http://www.ncbi.nlm.nih.gov/pubmed/23868195", "http://www.ncbi.nlm.nih.gov/pubmed/25699710", "http://www.ncbi.nlm.nih.gov/pubmed/24636987", "http://www.ncbi.nlm.nih.gov/pubmed/23251031", "http://www.ncbi.nlm.nih.gov/pubmed/22279048" ]

[]

[]

[ "M31 is a heterochromatin component, that is concentrated in the XY body during spermatogenesis. M31 overexpression has two contrasting effects which are dependent on chromosomal context: (i) it enhanced PEV in those lines with centromeric or pericentromeric transgene locations; and (ii) it suppressed PEV when the transgene was non-centromeric." ]

[]

[ "First, forced expression of full-length SUV39H1 (412 amino acids) redistributes endogenous M31 (HP1beta) and induces abundant associations with inter- and metaphase chromatin", "Together, our data reveal a dominant role(s) for the SET domain of SUV39H1 in the distribution of prominent heterochromatic proteins and suggest a possible link between a chromosomal SU(VAR) protein and histone H3", "Using this motif, termed chromo box, we have cloned a mouse candidate modifier gene, M31, that also shows considerable sequence homology to Drosophila HP1", "Here we report evidence of at least four independently segregating loci in the mouse homologous to the M31 cDNA. One of these loci--Cbx-rs1--maps to the X Chromosome (Chr), 1 cM proximal to Amg and outside the X-inactivation center region", "Although there is significant heterochromatic overlap between SUV39H1 and M31 (HP1(beta)) during interphase, mitotic SUV39H1 displays a more restricted spatial and temporal association pattern with metaphase chromosomes than M31 (HP1(beta)), or the related HP1(&agr;) gene product", "which complex with the heterochromatin component M31.", "In addition, Suv39h1/SUV39H1 proteins associate with M31, currently the only other characterized mammalian SU(VAR) homologue", "M31, a murine homolog of Drosophila HP1, is concentrated in the XY body during spermatogenesis", "The HP1 class of chromobox genes are thought to encode proteins involved in the packaging of chromosomal DNA into repressive heterochromatin domains, as seen, for example, in position-effect variegation", "Study of the distribution of a murine HP1-like chromodomain protein, M31, during spermatogenesis revealed spreading from the tip of the XY body in mid-stage pachytene spermatocytes to include the whole of the XY body in late-pachytene spermatocytes", "We also demonstrate that the formation of the XY body during spermatogenic progression in neonatal mice coincides with the expression of a novel nuclear isoform of M31, M31(p21", "Furthermore, by overexpressing a mammalian homologue (M31) of Drosophila melanogaster heterochromatin protein 1 (HP1; refs 7,8) in transgenic mouse lines that exhibit PEV, it is possible to modify the proportion of cells that silence the transgene in a dose-dependent manner", "Thus, we show M31 overexpression to have two contrasting effects which are dependent on chromosomal context: (i) it enhanced PEV in those lines with centromeric or pericentromeric transgene locations; and (ii) it suppressed PEV when the transgene was non-centromeric" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/10779362", "http://www.ncbi.nlm.nih.gov/pubmed/10671371", "http://www.ncbi.nlm.nih.gov/pubmed/10581035", "http://www.ncbi.nlm.nih.gov/pubmed/10516442", "http://www.ncbi.nlm.nih.gov/pubmed/1543904", "http://www.ncbi.nlm.nih.gov/pubmed/10202156" ]

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[ "http://www.uniprot.org/uniprot/CBX1_HUMAN", "http://www.uniprot.org/uniprot/CBX1_MOUSE", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D055012", "http://www.uniprot.org/uniprot/HXC8_MOUSE", "http://www.biosemantics.org/jochem#4262550" ]

[ "Yes, human cells can be used for bioprinting" ]

[ "yes" ]

[ "In this study, human adipose-derived stem cells (hASCs) were printed in a free-scalable 3D grid pattern by means of LaBP.", " Additionally, we provide the proof that even pre-differentiated hASCs could be utilized for the generation of 3D tissue grafts. ", "To explore the three dimensional(3D)bioprinting technology, using human dental pulp cells (hDPCs) mixture as bioink and to lay initial foundations for the application of the 3D bioprinting technology in tooth regeneration.", "In this study, 3-D printable formulations of hybrid hydrogels are developed, based on methacrylated hyaluronic acid (Me-HA) and methacrylated gelatin (Me-Gel), and used to bioprint heart valve conduits containing encapsulated human aortic valvular interstitial cells (HAVIC).", "Bioprinting can be used to precisely position cells and cell-laden materials to generate controlled tissue architecture.", "Bioprinting can be defined as the use of computer-aided transfer processes for patterning and assembling living and non-living materials with a prescribed 2D or 3D organization in order to produce bio-engineered structures serving in regenerative medicine, pharmacokinetic and basic cell biology studies.", "3D bioprinting has already been used for the generation and transplantation of several tissues, including multilayered skin, bone, vascular grafts, tracheal splints, heart tissue and cartilaginous structures.", "[Three dimensional bioprinting technology of human dental pulp cells mixtures].", "To explore the three dimensional(3D)bioprinting technology, using human dental pulp cells (hDPCs) mixture as bioink and to lay initial foundations for the application of the 3D bioprinting technology in tooth regeneration", "Here we report the development of clinically relevant sized tissue analogs by 3-D bioprinting, delivering human nasal inferior turbinate tissue-derived mesenchymal progenitor cells encapsulated in silk fibroin-gelatin (SF-G) bioink", "Sodium alginate hydrogel, stabilized with gelatin, is a suitable, biologically inert matrix that can be used for encapsulating and 3D bioprinting of bone-related SaOS-2 cells. ", "Bioactive nanoparticles stimulate bone tissue formation in bioprinted three-dimensional scaffold and human mesenchymal stem cells.", "OBJECTIVE: To explore the three dimensional(3D)bioprinting technology, using human dental pulp cells (hDPCs) mixture as bioink and to lay initial foundations for the application of the 3D bioprinting technology in tooth regeneration. ", "Cellular behavior in micropatterned hydrogels by bioprinting system depended on the cell types and cellular interaction.", "Engineering a morphogenetically active hydrogel for bioprinting of bioartificial tissue derived from human osteoblast-like SaOS-2 cells.", "At the same time, the principal feasibility of bioprinting vascularized human organs as well as in vivo bioprinting has been demonstrated.", "The bioprinting of complex 3D human tissues and constructs in vitro and especially in vivo are exciting, but long-term, applications.", "Bioprinting can be defined as the use of computer-aided transfer processes for patterning and assembling living and non-living materials with a prescribed 2D or 3D organization in order to produce bio-engineered structures serving in regenerative medicine, pharmacokinetic and basic cell biology studies.", "In this study, the 3D bioprinting of hDPCs mixtures was realized, thus laying initial foundations for the application of the 3D bioprinting technology in tooth regeneration.", "To explore the three dimensional(3D)bioprinting technology, using human dental pulp cells (hDPCs) mixture as bioink and to lay initial foundations for the application of the 3D bioprinting technology in tooth regeneration.", "Furthermore, it is not known how human valve cells respond to these printed environments. In this study, 3-D printable formulations of hybrid hydrogels are developed, based on methacrylated hyaluronic acid (Me-HA) and methacrylated gelatin (Me-Gel), and used to bioprint heart valve conduits containing encapsulated human aortic valvular interstitial cells (HAVIC).", "To explore the three dimensional(3D)bioprinting technology, using human dental pulp cells (hDPCs) mixture as bioink and to lay initial foundations for the application of the 3D bioprinting technology in tooth regeneration.", "[Three dimensional bioprinting technology of human dental pulp cells mixtures].", "The bioprinting of complex 3D human tissues and constructs in vitro and especially in vivo are exciting, but long-term, applications.", "Three-dimensional printed trileaflet valve conduits using biological hydrogels and human valve interstitial cells.", "Furthermore, it is not known how human valve cells respond to these printed environments.", "Engineering a morphogenetically active hydrogel for bioprinting of bioartificial tissue derived from human osteoblast-like SaOS-2 cells." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/25130390", "http://www.ncbi.nlm.nih.gov/pubmed/23197691", "http://www.ncbi.nlm.nih.gov/pubmed/20811115", "http://www.ncbi.nlm.nih.gov/pubmed/25242654", "http://www.ncbi.nlm.nih.gov/pubmed/25047630", "http://www.ncbi.nlm.nih.gov/pubmed/21504055", "http://www.ncbi.nlm.nih.gov/pubmed/24961492", "http://www.ncbi.nlm.nih.gov/pubmed/24998183", "http://www.ncbi.nlm.nih.gov/pubmed/23380571", "http://www.ncbi.nlm.nih.gov/pubmed/24695367", "http://www.ncbi.nlm.nih.gov/pubmed/23411530", "http://www.ncbi.nlm.nih.gov/pubmed/24157694", "http://www.ncbi.nlm.nih.gov/pubmed/24188635", "http://www.ncbi.nlm.nih.gov/pubmed/24334142", "http://www.ncbi.nlm.nih.gov/pubmed/25384685", "http://www.ncbi.nlm.nih.gov/pubmed/25457969", "http://www.ncbi.nlm.nih.gov/pubmed/23719889", "http://www.ncbi.nlm.nih.gov/pubmed/24439284", "http://www.ncbi.nlm.nih.gov/pubmed/22508498", "http://www.ncbi.nlm.nih.gov/pubmed/25093879", "http://www.ncbi.nlm.nih.gov/pubmed/22767299", "http://www.ncbi.nlm.nih.gov/pubmed/23575660", "http://www.ncbi.nlm.nih.gov/pubmed/23260439", "http://www.ncbi.nlm.nih.gov/pubmed/24903714", "http://www.ncbi.nlm.nih.gov/pubmed/23562089", "http://www.ncbi.nlm.nih.gov/pubmed/23015540", "http://www.ncbi.nlm.nih.gov/pubmed/20353253", "http://www.ncbi.nlm.nih.gov/pubmed/22394017", "http://www.ncbi.nlm.nih.gov/pubmed/21527813", "http://www.ncbi.nlm.nih.gov/pubmed/24758832", "http://www.ncbi.nlm.nih.gov/pubmed/22436025", "http://www.ncbi.nlm.nih.gov/pubmed/24887553", "http://www.ncbi.nlm.nih.gov/pubmed/23184715", "http://www.ncbi.nlm.nih.gov/pubmed/20546891", "http://www.ncbi.nlm.nih.gov/pubmed/25048797", "http://www.ncbi.nlm.nih.gov/pubmed/21358040" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D062028", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D006801", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D002477" ]

[ "Spontaneous point mutation rate in a gene increases with its transcription level, suggesting that movement of RNA polymerase through the target initiates a mutagenic process(es). This phenomenon is termed transcription-associated mutation (TAM). Transcription-associated mutagenesis is directly proportional to the level of gene expression." ]

[ "yes" ]

[ "These mutations were frequent in plasmid-borne lacS expressed at a high level but not in single-copy lacS in the chromosome or at lower levels of expression in a plasmid.", "The results suggest that important DNA repair or replication fidelity functions are impaired or overwhelmed in pJlacS, with results analogous to those of the \"transcription-associated mutagenesis\" seen in bacteria and eukaryotes.", "the rate of point mutation in a gene increases with the expression level of the gene. Transcription induces mutagenesis on both DNA strands, indicating simultaneous actions of several TAM mechanisms.", "High-levels of transcription through a gene stimulate spontaneous mutation rate, a phenomenon termed transcription-associated mutation (TAM).", "High levels of transcription in Saccharomyces cerevisiae are associated with increased genetic instability, which has been linked to DNA damage. Here, we describe a pGAL-CAN1 forward mutation assay for studying transcription-associated mutagenesis (TAM) in yeast.", "The acquisition of mutations was directly correlated to the level of transcription", "Our results demonstrate that the level of Leu(+) reversions increased significantly in parallel with the induced increase in transcription levels.", "Transcription-associated mutagenesis in yeast is directly proportional to the level of gene expression", "spontaneous mutation rate is directly proportional to the transcription level, suggesting that movement of RNA polymerase through the target initiates a mutagenic process(es)", "High transcription is associated with genetic instability, notably increased spontaneous mutation rates, which is a phenomenon termed Transcription-Associated-Mutagenesis (TAM).", "Using this system, we also investigated two hypotheses that have been proposed to explain transcription-associated mutagenesis (TAM): (1) transcription impairs replication fork progression in a directional manner and (2) DNA lesions accumulate under high-transcription conditions.", "Transcription-associated mutagenesis in yeast is directly proportional to the level of gene expression and influenced by the direction of DNA replication.", "High levels of transcription in Saccharomyces cerevisiae are associated with increased genetic instability, which has been linked to DNA damage.", "Using this system, we also investigated two hypotheses that have been proposed to explain transcription-associated mutagenesis (TAM): (1) transcription impairs replication fork progression in a directional manner and (2) DNA lesions accumulate under high-transcription conditions.", "Using comparative genomics of related species as well as mutation accumulation lines, we show in yeast that the rate of point mutation in a gene increases with the expression level of the gene", "High transcription is associated with genetic instability, notably increased spontaneous mutation rates, which is a phenomenon termed Transcription-Associated-Mutagenesis (TAM)", "Using this system, we also investigated two hypotheses that have been proposed to explain transcription-associated mutagenesis (TAM): (1) transcription impairs replication fork progression in a directional manner and (2) DNA lesions accumulate under high-transcription conditions", "High-levels of transcription through a gene stimulate spontaneous mutation rate, a phenomenon termed transcription-associated mutation (TAM)" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/23146897", "http://www.ncbi.nlm.nih.gov/pubmed/21177427", "http://www.ncbi.nlm.nih.gov/pubmed/21177431", "http://www.ncbi.nlm.nih.gov/pubmed/17398168", "http://www.ncbi.nlm.nih.gov/pubmed/23055242", "http://www.ncbi.nlm.nih.gov/pubmed/10628973", "http://www.ncbi.nlm.nih.gov/pubmed/23564176", "http://www.ncbi.nlm.nih.gov/pubmed/20435731", "http://www.ncbi.nlm.nih.gov/pubmed/15143174" ]

[]

[ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0010467", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0006351" ]

[ "Yes. HER2 testing is performed in breast cancer patients to determine suitability for trastuzumab (Herceptin therapy)." ]

[ "yes" ]

[ "The clinical need for novel approaches to improve drug therapy derives from the high rate of adverse reactions to drugs and their lack of efficacy in many individuals that may be predicted by pharmacogenetic testing.", "the assessment of the human epidermal growth factor receptor (HER-2) expression for trastuzumab therapy of breast cancer", "HER2 positive breast cancer and the use of the drug Herceptin", "The dependence on gene copy number or expression levels of HER2 and epidermal growth factor receptor (EGFR) for therapeutic efficacy of trastuzumab and cetuximab (Erbitux), respectively, supports the importance of selecting suitable patient populations based on their pharmacogenetic profile.", "to explore informed consent issues surrounding the use of the drug Herceptin, widely cited as an example of a novel approach to drug development called pharmacogenetics. Drawing on qualitative semi-structured interviews with 25 UK-based breast cancer specialists, this paper explores Herceptin's disputed epistemological status, as an example of pharmacogenetics or as something out of the ordinary in terms of clinical practice.", "There have been several success stories in the field of pharmacogenetics in recent years, including the analysis of HER2 amplification for trastuzumab selection in breast cancer", "Trastuzumab is standard of care in the treatment of human epidermal growth factor receptor (HER)-2⁺ early and advanced breast cancer.", "HER-2 overexpression as a predictor of response to trastuzumab", "Pharmacogenomic analysis aspires to identify individuals with specific genetic characteristics in order to predict a positive response or reduce a negative response to a therapeutic modality.", "Assays are available to detect the HER2 protein receptor or copies of the HER2 gene sequence to determine eligibility for Herceptin treatment or adriamycin treatment in node positive patients, respectively.", "Determining the HER2 status of breast carcinomas is a prerequisite for the use of the monoclonal antibody trastuzumab (Herceptin), which has recently been licensed for the treatment of metastatic disease.", "Laboratory testing of HER2/neu in breast carcinoma has become vital to patient care following the approval of trastuzumab as the first therapy to target the HER2/neu oncoprotein.", "Immunohistochemical (IHC) analysis was performed with use of a diagnostic test for the assessment of HER2 overexpression, the HercepTest.", "To test for HER-2/neu overexpression in patients with non-Hodgkin's lymphoma and the possible role of the recombinant monoclonal anti-HER-2/neu antibody trastuzumab (Herceptin) in the treatment of non-Hodgkin's lymphoma.", "To evaluate concordance between local and central laboratory HER2 testing results in patients from the North Central Cancer Treatment Group (NCCTG) N9831 adjuvant trial of trastuzumab.", "These findings support the importance of using high-volume, experienced laboratories for HER2 testing to improve the process of selecting patients likely to benefit from trastuzumab therapy.", "we measured trastuzumab levels in the serum and in cerebrospinal fluid of metastatic breast cancer patients with brain metastases receiving trastuzumab for HER2-overexpressing metastatic breast cancer. In a pilot study, metastatic breast cancer patients with brain metastases and HER2-overexpressing tumors (HercepTest; Dako, Copenhagen, Denmark) were included.", "Monitoring of trastuzumab levels in the serum and cerebrospinal fluid may enable individualized therapy strategies in metastatic breast cancer patients with brain metastases, and lead to a better understanding of trastuzumab pharmacokinetics in the cerebrospinal fluid and serum.", "Biotin-labeled trastuzumab (BiotHER) can be used to test for HER2 by immunohistochemistry.", "The results support a role for BiotHER testing in better tailoring trastuzumab-based treatments in patients with advanced HER2-amplified breast cancers.", "response to anti-human epidermal growth factor receptor 2 (HER2) therapy trastuzumab." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/20590449", "http://www.ncbi.nlm.nih.gov/pubmed/16809727", "http://www.ncbi.nlm.nih.gov/pubmed/11838648", "http://www.ncbi.nlm.nih.gov/pubmed/17785760", "http://www.ncbi.nlm.nih.gov/pubmed/11265171", "http://www.ncbi.nlm.nih.gov/pubmed/15970231", "http://www.ncbi.nlm.nih.gov/pubmed/16235569", "http://www.ncbi.nlm.nih.gov/pubmed/15510616", "http://www.ncbi.nlm.nih.gov/pubmed/21632460", "http://www.ncbi.nlm.nih.gov/pubmed/22461093", "http://www.ncbi.nlm.nih.gov/pubmed/17159499", "http://www.ncbi.nlm.nih.gov/pubmed/17947471", "http://www.ncbi.nlm.nih.gov/pubmed/17184417", "http://www.ncbi.nlm.nih.gov/pubmed/11579337", "http://www.ncbi.nlm.nih.gov/pubmed/11097337", "http://www.ncbi.nlm.nih.gov/pubmed/22065003", "http://www.ncbi.nlm.nih.gov/pubmed/15217485", "http://www.ncbi.nlm.nih.gov/pubmed/22112244" ]

[ { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#type", "s": "http://linkedlifedata.com/resource/umls/label/A10771788", "o": "http://www.w3.org/2008/05/skos-xl#Label" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A1545807", "o": "trastuzumab" }, { "p": "http://linkedlifedata.com/resource/umls/altMetaMap", "s": "http://linkedlifedata.com/resource/umls/id/C0728747", "o": "http://linkedlifedata.com/resource/umls/label/A10771788" }, { "p": "http://www.w3.org/1999/02/22-rdf-syntax-ns#type", "s": "http://linkedlifedata.com/resource/umls/label/A8438296", "o": "http://www.w3.org/2008/05/skos-xl#Label" }, { "p": "http://www.w3.org/2008/05/skos-xl#literalForm", "s": "http://linkedlifedata.com/resource/umls/label/A16756458", "o": "TRASTUZUMAB" }, { "p": "http://www.w3.org/2004/02/skos/core#exactMatch", "s": "http://www4.wiwiss.fu-berlin.de/drugbank/resource/drugs/DB00072", "o": "http://dbpedia.org/resource/Trastuzumab" } ]

[ "http://www.biosemantics.org/jochem#4002084", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D010597" ]

[ "Ethosuximide blocks the T-type calcium channels." ]

[ "T-type calcium channels" ]

[ "In the present study, we examined whether ethosuximide (ETX), a T-channel antagonist, could decrease the severity of ethanol withdrawal seizures by evaluating electrographical and behavioral correlates of seizure activity.", "In rats, intraplantar (i.pl.) administration of db-cAMP or PGE(2) caused mechanical hyperalgesia, an effect suppressed by AKAPI, two distinct T-channel blockers, NNC 55-0396 and ethosuximide, or ZnCl(2) , known to inhibit Ca(v) 3.2 among T channels.", "Theta rhythms remained disrupted during a subsequent week of withdrawal but were restored with the T-type channel blocker ethosuximide.", "Given evidence that chemotherapy-induced neuropathic pain is blocked by ethosuximide, known to block T-type calcium channels, we examined if more selective T-type calcium channel blockers and also inhibitors of cystathionine-γ-lyase (CSE), a major H₂S-forming enzyme in the peripheral tissue, are capable of reversing the neuropathic pain evoked by paclitaxel, an anti-cancer drug.", "The results demonstrate that both ethosuximide and the active metabolite of methsuximide, alpha-methyl-alpha-phenylsuccinimide (MPS), block human T-type channels in a state-dependent manner, with higher affinity for inactivated channels.", "T-type channels display current at the end of long pulses (persistent current), and this current was especially sensitive to block (ethosuximide IC(50) = 0.6 mM).", "We tested the effects of several T-type calcium channel blockers, including zonisamide (ZNS), ethosuximide, lomerizine, amiloride, mibefradil, and NCC 55-0396, a mibefradil derivative, on tacrine-induced tremulous jaw movements (TJMs), an animal model of parkinsonian tremor.", "The antihyperalgesic effects of the T-type calcium channel blockers ethosuximide, trimethadione, and mibefradil.", "Gallopamil and another T-type-channel blocker, ethosuximide, were included for comparison.", "The Ca(v)3.2 channel is sensitive to ethosuximide, amlodipine and amiloride.", "The purpose of the present study was to explore the analgesic effects of the low voltage-activated T-type Ca2+ channel blockers ethosuximide, trimethadione, and mibefradil in persistent and acute nociceptive tests.", "We tested the effects of several T-type calcium channel blockers, including zonisamide (ZNS), ethosuximide, lomerizine, amiloride, mibefradil, and NCC 55-0396, a mibefradil derivative, on tacrine-induced tremulous jaw movements (TJMs), an animal model of parkinsonian tremor. ", "We focused on two T-type calcium blockers, trimethadione and ethosuximide, which are anti-epileptics approved by the Food and Drug Administration. ", "Gallopamil and another T-type-channel blocker, ethosuximide, were included for comparison. " ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/15638774", "http://www.ncbi.nlm.nih.gov/pubmed/21112351", "http://www.ncbi.nlm.nih.gov/pubmed/21596106", "http://www.ncbi.nlm.nih.gov/pubmed/10882031", "http://www.ncbi.nlm.nih.gov/pubmed/17291698", "http://www.ncbi.nlm.nih.gov/pubmed/24933286", "http://www.ncbi.nlm.nih.gov/pubmed/11641441", "http://www.ncbi.nlm.nih.gov/pubmed/15078185", "http://www.ncbi.nlm.nih.gov/pubmed/26089446", "http://www.ncbi.nlm.nih.gov/pubmed/22924591", "http://www.ncbi.nlm.nih.gov/pubmed/19005061", "http://www.ncbi.nlm.nih.gov/pubmed/16171802", "http://www.ncbi.nlm.nih.gov/pubmed/21148095" ]

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[ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D020747", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D005013", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D015220", "http://www.biosemantics.org/jochem#4249275" ]

[ "The mammalian mitochondrial ribosome (mitoribosome) has a highly protein-rich composition with a small sedimentation coefficient of 55 S, consisting of 39 S large and 28 S small subunits." ]

[ "55 S" ]

[ " The mammalian mitochondrial ribosomes (55S)", "The mammalian mitochondrial ribosome (mitoribosome) has a highly protein-rich composition with a small sedimentation coefficient of 55 S, consisting of 39 S large and 28 S small subunits.", "The 55 S mammalian mitochondrial ribosome (referred to hereafter as \"mitoribosome\") is protein-rich, containing nearly twice as much protein as the Escherichia coli ribosome. ", "59 of 78 proteins of the 55S mitoribosome, several TIM and TOM proteins and cell death proteins were present.", "The sedimentation coefficient of the intact monosome was about 55 S. ", "Though the nematode mitoribosome has a larger size than the bacterial ribosome, it does not differ significantly in size from mammalian mitoribosomes.", "The mammalian mitochondrial (mt) ribosome (mitoribosome) is a bacterial-type ribosome but has a highly protein-rich composition." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/11402041", "http://www.ncbi.nlm.nih.gov/pubmed/15966747", "http://www.ncbi.nlm.nih.gov/pubmed/11943462", "http://www.ncbi.nlm.nih.gov/pubmed/14757048", "http://www.ncbi.nlm.nih.gov/pubmed/6284743", "http://www.ncbi.nlm.nih.gov/pubmed/19567276" ]

[]

[ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0005762", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0005761", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012270", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0005840", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0003735" ]

[ "Aliskiren is a low-molecular-weight, orally active, hydrophilic non-peptide molecule that blocks renin and consequential angiotensin I generation. Renin inhibition interrupts the renin-angiotensin-aldosterone system (RAAS)." ]

[]

[ "Preliminary assignment a direct renin inhibitor aliskiren enhances the diuretic, natriuretic and kaliyuretic effects of the drug. ", "Aliskiren: An orally active renin inhibitor.", "Optimization of this compound by Novartis led to the development of aliskiren - the only direct renin inhibitor which is clinically used as an antihypertensive drug.", "Aliskiren is a new renin inhibitor of a novel structural class that has recently been shown to be efficacious in hypertensive patients after once-daily oral dosing.", "Aliskiren is a direct renin inhibitor that interrupts the renin-angiotensin-aldosterone system (RAAS) at its rate-limiting step.", "THE READER WILL GAIN: Aliskiren, the first approved renin inhibitor to reach the market, is a low-molecular-weight, orally active, hydrophilic non-peptide molecule that blocks angiotensin I generation. ", "TAKE HOME MESSAGE: The DRI aliskiren is an effective antihypertensive agent that preliminary data suggests has a beneficial effect in CVD and CKD. ", "Aliskiren is a novel molecule which blocks the renin-angiotensin-aldosterone system in its rate limiting step by renin inhibition.", "After discovery of the first direct renin inhibitor, aliskiren, which blocks the renin-angiotensin-aldosterone system in the first rate limiting step, in addition to angiotensin-converting enzymes (ACE) and angiotensin-receptor blockers (ARB), renin has become an important target nowadays. ", "Aliskiren, the first orally effective direct renin inhibitor, is an effective antihypertensive agent with distinctive properties including placebo-like tolerability, pharmacologic effects that persist after drug discontinuation, and a unique mechanism of action.", "Aliskiren, the first direct renin inhibitor to reach the market, is a low-molecular-weight, orally active, hydrophilic nonpeptide. Aliskiren blocks Ang I generation, while plasma renin concentration increases because the drugs blocks the negative feed-back exerted by Ang II on renin synthesis.", "Pharmacokinetics and pharmacodynamics of aliskiren, an oral direct renin inhibitor.", "One drug that emerged from this effort is aliskiren, a direct human renin inhibitor that blocks the conversion of angiotensinogen to angiotensin I (Ang I).", "With its unique mechanism of action, combining aliskiren with another RAAS-blocking agent that has a different mechanism of action may provide more comprehensive blockade of the RAAS, potentially conferring additional clinical benefits.", "In the ALTITUDE trial the use of the direct renin inhibitor, aliskiren, was associated with hypotensive episodes and an excess of ischaemic stroke", "Renin is the rate limiting enzyme of the RAAS and aliskiren is a highly potent and selective inhibitor of the human renin", "Aliskiren, the first direct renin inhibitor to be approved for the treatment of hypertension, blocks the RAAS at its point of activation", "With its unique mechanism of action, combining aliskiren with another RAAS-blocking agent that has a different mechanism of action may provide more comprehensive blockade of the RAAS, potentially conferring additional clinical benefits" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/19183745", "http://www.ncbi.nlm.nih.gov/pubmed/19895758", "http://www.ncbi.nlm.nih.gov/pubmed/23355128", "http://www.ncbi.nlm.nih.gov/pubmed/20812878", "http://www.ncbi.nlm.nih.gov/pubmed/23087256", "http://www.ncbi.nlm.nih.gov/pubmed/20467589", "http://www.ncbi.nlm.nih.gov/pubmed/25534713", "http://www.ncbi.nlm.nih.gov/pubmed/21687346", "http://www.ncbi.nlm.nih.gov/pubmed/23438929", "http://www.ncbi.nlm.nih.gov/pubmed/23723254", "http://www.ncbi.nlm.nih.gov/pubmed/18374681", "http://www.ncbi.nlm.nih.gov/pubmed/20380486", "http://www.ncbi.nlm.nih.gov/pubmed/21285669", "http://www.ncbi.nlm.nih.gov/pubmed/23418282", "http://www.ncbi.nlm.nih.gov/pubmed/22522051", "http://www.ncbi.nlm.nih.gov/pubmed/19337534", "http://www.ncbi.nlm.nih.gov/pubmed/24003484", "http://www.ncbi.nlm.nih.gov/pubmed/20019471", "http://www.ncbi.nlm.nih.gov/pubmed/20019472", "http://www.ncbi.nlm.nih.gov/pubmed/19066408", "http://www.ncbi.nlm.nih.gov/pubmed/23764715", "http://www.ncbi.nlm.nih.gov/pubmed/20203685", "http://www.ncbi.nlm.nih.gov/pubmed/20675959", "http://www.ncbi.nlm.nih.gov/pubmed/18443751", "http://www.ncbi.nlm.nih.gov/pubmed/21779913", "http://www.ncbi.nlm.nih.gov/pubmed/23174623", "http://www.ncbi.nlm.nih.gov/pubmed/22387646", "http://www.ncbi.nlm.nih.gov/pubmed/19279548", "http://www.ncbi.nlm.nih.gov/pubmed/21628356", "http://www.ncbi.nlm.nih.gov/pubmed/20957132" ]

[]

[ "http://www.biosemantics.org/jochem#4240636" ]

[ "Prokaryotic histone-like proteins (Hlps) or nucleoid-associated proteins (NAPs) are abundant proteins found in bacterial and plastid nucleoids. HU protein is a small, basic, heat-stable DNA-binding protein that is well-conserved in prokaryotes and is associated with the bacterial nucleoid. HU is well conserved in all prokaryotes but surprisingly, it is also homologous to another E. coli DNA-binding protein, IHF. In prokaryotes, IHF and HU are key architectural proteins present at high concentrations. Histone-like Nucleoid Structuring (H-NS) protein can facilitate correct recognition of a promoter by RNA polymerase in AT-rich gene regulatory regions", "THe histone-like proteins HU, IHF, H-NS (Nucleoid Structuring) act as histones in prokaryotes" ]

[ "HU", "IHF", "H-NS" ]

[ "We show that Histone-like Nucleoid Structuring (H-NS) protein can facilitate correct recognition of a promoter by RNA polymerase in AT-rich gene regulatory regions", "One feature is a histone-like protein that is associated with the DNA, condensing it into subunits similar to those in eukaryotic chromatin", "Recently the histone-like proteins were found in some primitive eucaryotes and procaryotes", "The relationship between HMGs (1 + 2) and the \"primitive\" histone-like DNA-packaging proteins from prokaryotes and mitochondria is discussed", "The amino acid composition of the protein resembled those of the other prokaryotic histone-like proteins and also to eukaryotic histones H2A and H2B", "In prokaryotes and in the pool of vegetative phage DNA the most abundant histone-like protein HU is not associated with the bulk DNA, but localised in the border region with ribosomes where transcription and translation occur", "Like the histones, HU is able to condense DNA in vitro and to introduce negative super-coiling in covalently closed circular, relaxed DNA molecules in the presence of topoisomerase I", "HU is well conserved in all prokaryotes but surprisingly, it is also homologous to another E. coli DNA-binding protein, IHF", "Here we describe the identification of two developmental stage-specific genes, one of which is predicted to encode a 26-kDa lysine- and alanine-rich protein that appears to be homologous to several eukaryotic histone H1 proteins", "No sequence homology was observed between this protein and other bacterial \"histone-like\" chromosomal proteins, but homology does exist with two other recently described prokaryotic proteins", "In this study we show that these proteins can substitute for the prokaryotic DNA-bending protein HU in promoting the assembly of the Hin invertasome, an intermediate structure in Hin-mediated site-specific DNA inversion", "We have characterized the role of HU in assembling the invertasome, an intermediate nucleoprotein complex involved in Hin-mediated site-specific recombination", "Using ligase-mediated circularization of short DNA fragments we also show that HU, the high mobility group (HMG) 1 and 2 proteins from mammals, and a protein from yeast can bend DNA extremely efficiently", "The repression of transcription of two overlapping promoters of the gal operon in Escherichia coli requires Gal repressor (GalR) and the histone-like protein HU", "We report GalR mediated DNA looping in which HU plays an obligatory role by helping GalR tetramerization", "The protein has unique dual domains with homology to both bacterial histone-like proteins (HU) and eukaryotic histone H1", " Four out of seven multi-copy suppressors were identified to encode HU, (3 for HUalpha and 1 for HUB) a histone-like DNA binding protein", "oles of Escherichia coli histone-like protein HU in DNA replication", "HU protein is a small, basic, heat-stable DNA-binding protein that is well-conserved in prokaryotes and is associated with the bacterial nucleoid", "role of surface-exposed lysines in wrapping DNA about the bacterial histone-like protein HU", "basic proteins, including the ubiquitous HU proteins, serve histone-like functions in prokaryotes", "modification of E. coli histone-like protein H-NS and bovine histones by short-chain poly-(R)-3-hydroxybutyrate (cPHB)", "Here we examine Escherichia coli protein H-NS and calf thymus histones, H1, H2A, H2B, H3, and H4, for the presence of cPHB", "The process requires negatively supercoiled DNA and the presence of the histone-like protein HU", "Characterization of the major DNA-binding proteins of nucleoids revealed essential differences in the two lineages of photosynthetic eukaryotes, namely nucleoids of green plants contain sulfite reductase as a major DNA-binding protein that represses the genomic activity, whereas the prokaryotic DNA-binding protein HU is abundant in plastid nucleoids of the rhodophyte lineage", "In prokaryotes, IHF and HU are key architectural proteins present at high concentrations", "The deficit of TFs in some genomes might be compensated by the presence of proteins organizing and compacting DNA, such as histone-like proteins", "okaryotic histone-like proteins (Hlps) are abundant proteins found in bacterial and plastid nucleoids", "n mesophilic prokaryotes, the DNA-binding protein HU participates in nucleoid organization as well as in regulation of DNA-dependent processes", "We show here that HU from the hyperthermophilic eubacterium Thermotoga maritima HU bends DNA and constrains negative DNA supercoils in the presence of topoisomerase I", " We suggest that T. maritima HU serves an architectural function when associating with a single 35 bp site, but generates a very stable and compact aggregate at higher protein concentrations that organizes and protects the genomic DNA", "ittle is known about the structure and function of most nucleoid-associated proteins (NAPs) in bacteria", "n this study, we investigate the distribution of HU in Caulobacter crescentus using a combination of super-resolution fluorescence imaging and spatial point statistics" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/14596799", "http://www.ncbi.nlm.nih.gov/pubmed/6253884", "http://www.ncbi.nlm.nih.gov/pubmed/23818873", "http://www.ncbi.nlm.nih.gov/pubmed/12220682", "http://www.ncbi.nlm.nih.gov/pubmed/3282561", "http://www.ncbi.nlm.nih.gov/pubmed/9016640", "http://www.ncbi.nlm.nih.gov/pubmed/11278072", "http://www.ncbi.nlm.nih.gov/pubmed/1925023", "http://www.ncbi.nlm.nih.gov/pubmed/15556475", "http://www.ncbi.nlm.nih.gov/pubmed/10645441", "http://www.ncbi.nlm.nih.gov/pubmed/16911001", "http://www.ncbi.nlm.nih.gov/pubmed/1549572", "http://www.ncbi.nlm.nih.gov/pubmed/656568", "http://www.ncbi.nlm.nih.gov/pubmed/14711120", "http://www.ncbi.nlm.nih.gov/pubmed/8339930", "http://www.ncbi.nlm.nih.gov/pubmed/667214", "http://www.ncbi.nlm.nih.gov/pubmed/6294066", "http://www.ncbi.nlm.nih.gov/pubmed/15102446", "http://www.ncbi.nlm.nih.gov/pubmed/18515342", "http://www.ncbi.nlm.nih.gov/pubmed/7748943", "http://www.ncbi.nlm.nih.gov/pubmed/11075932", "http://www.ncbi.nlm.nih.gov/pubmed/12056890", "http://www.ncbi.nlm.nih.gov/pubmed/21463569" ]

[]

[ "http://www.uniprot.org/uniprot/HNS_ECO57", "http://www.uniprot.org/uniprot/H33L2_CAEEL", "http://www.uniprot.org/uniprot/HLP_RICCN", "http://www.uniprot.org/uniprot/H2AZL_XENTR", "http://www.uniprot.org/uniprot/H13_CAEEL", "http://www.uniprot.org/uniprot/HNS_SALPA", "http://www.uniprot.org/uniprot/HLP_RICMO", "http://www.uniprot.org/uniprot/H33L1_CAEEL", "http://www.uniprot.org/uniprot/HNS_SALTI", "http://www.uniprot.org/uniprot/HLP_RICTY", "http://www.uniprot.org/uniprot/HLP_RICRI", "http://www.uniprot.org/uniprot/HLP_RICPR", "http://www.uniprot.org/uniprot/H3L_ENCCU", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D006657", "http://www.uniprot.org/uniprot/DBH_GUITH", "http://www.uniprot.org/uniprot/HNS_SALTY", "http://www.uniprot.org/uniprot/HQ1_COXBU", "http://www.uniprot.org/uniprot/H3L3_LILLO", "http://www.uniprot.org/uniprot/DBH_MYCS2", "http://www.uniprot.org/uniprot/H3L2_LILLO", "http://www.uniprot.org/uniprot/HNS_PROVU", "http://www.uniprot.org/uniprot/B4_XENLA", "http://www.uniprot.org/uniprot/YMOA_YERPE", "http://www.biosemantics.org/jochem#4278518", "http://www.uniprot.org/uniprot/H3L5_ARATH", "http://www.uniprot.org/uniprot/HDAH_ALCSD", "http://www.uniprot.org/uniprot/H16_CAEEL", "http://www.uniprot.org/uniprot/H3L2_ARATH", "http://www.uniprot.org/uniprot/H14_CAEEL", "http://www.uniprot.org/uniprot/HNS_ECOLI", "http://www.uniprot.org/uniprot/DBH_MYCLE", "http://www.uniprot.org/uniprot/H15_CAEEL", "http://www.uniprot.org/uniprot/H3L1_LILLO", "http://www.uniprot.org/uniprot/DBH_MYCBO", "http://www.uniprot.org/uniprot/YMOA_YEREN", "http://www.uniprot.org/uniprot/HNS_ECOL6", "http://www.uniprot.org/uniprot/HLP_RICBR", "http://www.uniprot.org/uniprot/HNS_SERMA", "http://www.uniprot.org/uniprot/SKP_ECOLI", "http://www.uniprot.org/uniprot/H3L4_ARATH", "http://www.uniprot.org/uniprot/H3L1_ARATH", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011387", "http://www.uniprot.org/uniprot/H3L3_ARATH", "http://www.uniprot.org/uniprot/H3CL_BOVIN", "http://www.uniprot.org/uniprot/18C_DROME", "http://www.uniprot.org/uniprot/DBH_MYCTU", "http://www.uniprot.org/uniprot/H12_CAEEL", "http://www.uniprot.org/uniprot/HC2D_CHLTR", "http://www.uniprot.org/uniprot/HLP_RICFE", "http://www.uniprot.org/uniprot/H2AZL_XENLA", "http://www.uniprot.org/uniprot/H1X_CAEEL" ]

[ "Telcagepant (MK-0974) is a novel calcitonin gene-related peptide (CGRP) receptor antagonist currently undergoing clinical trials for migraine." ]

[ "calcitonin gene-related peptide" ]

[ "In vivo quantification of calcitonin gene-related peptide receptor occupancy by telcagepant in rhesus monkey and human brain using the positron emission tomography tracer [11C]MK-4232.", "Lack of hemodynamic interaction between CGRP-receptor antagonist telcagepant (MK-0974) and sumatriptan: results from a randomized study in patients with migraine.", "Olcegepant is the first selective CGRP receptor antagonist of proven efficacy in migraine. Olcegepant could only be administered intravenously and never taken beyond Phase II. Telcagepant is orally available and several completed Phase III trials have revealed positive results. ", "Telcagepant (MK-0974) is a novel calcitonin gene-related peptide (CGRP) receptor antagonist currently undergoing clinical trials for migraine (http://www.merck.com/research/pipeline/home.html).", "Four chemically unrelated CGRP receptor (CGRP-R) antagonists (olcegepant, telcagepant, MK-3207 and BI 44370 TA) have displayed efficacy in the treatment of migraine. ", "Telcagepant is a calcitonin gene-related peptide (CGRP) receptor antagonist being evaluated for acute migraine treatment. ", "BACKGROUND: Calcitonin gene-related peptide receptor antagonists, such as telcagepant, may be useful for acute migraine treatment in patients with cardiovascular disease, a population for whom triptans are contraindicated.", "The calcitonin gene-related peptide (CGRP) receptor antagonists (gepants)-olcegepant (BIBN 4096 BS), telcagepant (MK-0974), MK3207, and BI 44370 TA-are effective in treating acute migraine. ", "Telcagepant, a calcitonin gene-related peptide receptor antagonist, is being developed for the acute treatment of migraine. ", "The potent calcitonin gene-related peptide receptor antagonist, telcagepant, does not affect nitroglycerin-induced vasodilation in healthy men.", "AIMS: To assess the effect of the calcitonin gene-related peptide (CGRP) receptor antagonist, telcagepant, on the haemodynamic response to sublingual nitroglycerin (NTG). ", "BACKGROUND: Telcagepant is an oral calcitonin gene-related peptide receptor antagonist which is being evaluated for the acute treatment of migraine. ", "BACKGROUND: The calcitonin gene-related peptide (CGRP) receptor antagonists olcegepant and telcagepant are very potent drugs. ", "CONCLUSION: The apparently high doses of CGRP receptor antagonists, olcegepant and telcagepant needed for anti-migraine effect are not so high after all. ", "Dose-response curves for headaches relief and adverse events (AEs) are presented for five triptans: sumatriptan, zolmitriptan, naratriptan, almotriptan, and frovatriptan, and the CGRP antagonist telcagepant.", "INTRODUCTION: Telcagepant (MK-0974) is a novel, orally active and selective CGRP receptor antagonist being investigated for acute treatment of migraine.", "Calcitonin gene-related peptide (CGRP) receptor antagonists are another promising nonvasoconstrictor approach to treating acute migraine. Olcegepant (BIBN4096BS) and telcagepant (MK-0974) have been shown to be safe and effective in phase I, II, and (for telcagepant) phase III clinical trials. ", "Background.- Telcagepant is a calcitonin gene-related peptide (CGRP) receptor antagonist being investigated for the acute treatment of migraine.", "In 3 randomized clinical trials (n = 1585) the calcitonin gene-related peptide antagonist telcagepant 300 mg orally had an incidence of adverse events similar to placebo when used in the acute treatment of migraine. ", "BACKGROUND: Telcagepant is an oral calcitonin gene-related peptide receptor antagonist with acute antimigraine efficacy comparable to oral triptans", "METHODS: This study evaluated the calcitonin gene-related peptide (CGRP) receptor antagonist telcagepant (tablet formulation) for treatment of a migraine attack and across four attacks.", "A highly efficient, asymmetric synthesis of telcagepant (1), a CGRP receptor antagonist for the treatment of migraine, is described", "Asymmetric synthesis of telcagepant, a CGRP receptor antagonist for the treatment of migraine.", "Sustained pain freedom and no adverse events as an endpoint in clinical trials of acute migraine treatments: application to patient-level data from a trial of the CGRP receptor antagonist, telcagepant, and zolmitriptan.", "METHODS: The aim of this study was to evaluate new composite efficacy-plus-tolerability endpoints based on a post-hoc analysis of patient-level data from a previous randomized, placebo-controlled trial of the calcitonin gene-related peptide (CGRP) receptor antagonist, telcagepant, and zolmitriptan in the acute treatment of migraine.", "Effect of the calcitonin gene-related peptide (CGRP) receptor antagonist telcagepant in human cranial arteries.", "MATERIALS AND METHODS: We investigated the effect of the CGRP receptor antagonist, telcagepant, on CGRP-induced cranial vasodilatation in human isolated cerebral and middle meningeal arteries. ", "CONCLUSIONS: Our findings provide morphological and functional data on the presence of CGRP receptors in cerebral and meningeal arteries, which illustrates a possible site of action of telcagepant in the treatment of migraine.", "Characterization of the calcitonin gene-related peptide receptor antagonist telcagepant (MK-0974) in human isolated coronary arteries.", "We therefore investigated the effects of the antimigraine CGRP receptor antagonist telcagepant (MK-0974) [N-[(3R,6S)-6-(2,3-difluorophenyl)-2-oxo-1-(2,2,2-trifluoroethyl)azepan-3-yl]-4-(2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridine-1-yl)piperidine-1-carboxamide] on human isolated coronary arteries. ", "These findings in vitro support the cardiovascular safety of CGRP receptor antagonists and suggest that telcagepant is unlikely to induce coronary side effects under normal cardiovascular conditions.", "Towards this end, the non-peptide CGRP receptor antagonists olcegepant and telcagepant have been shown to be effective in the acute treatment of migraine. While telcagepant is being pursued as a frontline abortive migraine drug in a phase III clinical trial, an oral formulation of a novel CGRP receptor antagonist, BI 44370, is currently in phase II clinical trials.", "Telcagepant represents a new class of antimigraine drug-the calcitonin gene-related peptide receptor blockers. ", "The CGRP receptor antagonists telcagepant and olcegepant (BIBN4096BS) have demonstrated clinical efficacy in the treatment of migraine and there is now a need to better understand how these molecules interact with the receptor. ", "Single- and multiple-dose pharmacokinetics and tolerability of telcagepant, an oral calcitonin gene-related peptide receptor antagonist, in adults.", "Telcagepant is a novel, orally active, and selective calcitonin gene-related peptide receptor antagonist being developed for acute treatment of migraine with and without aura. ", "Studies were conducted in human isolated coronary arteries to explore the vascular effects of the calcitonin gene-related peptide (CGRP) receptor antagonist telcagepant and to compare its coronary vasoconstrictive potential to that of zolmitriptan. ", "Intravenous BIBN4096BS (olcegepant) and oral MK-0974 (telcagepant), two CGRP-receptor antagonists, were safe and effective in the treatment of migraine attacks in Phase I and II trials. ", "Telcagepant (MK-0974) is a novel oral calcitonin gene-related peptide (CGRP) receptor antagonist and is currently under clinical development." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/21350792", "http://www.ncbi.nlm.nih.gov/pubmed/23196486", "http://www.ncbi.nlm.nih.gov/pubmed/20416945", "http://www.ncbi.nlm.nih.gov/pubmed/23480465", "http://www.ncbi.nlm.nih.gov/pubmed/23975906", "http://www.ncbi.nlm.nih.gov/pubmed/19157980", "http://www.ncbi.nlm.nih.gov/pubmed/21070230", "http://www.ncbi.nlm.nih.gov/pubmed/21480950", "http://www.ncbi.nlm.nih.gov/pubmed/21110235", "http://www.ncbi.nlm.nih.gov/pubmed/19939188", "http://www.ncbi.nlm.nih.gov/pubmed/20099900", "http://www.ncbi.nlm.nih.gov/pubmed/19795182", "http://www.ncbi.nlm.nih.gov/pubmed/18799366", "http://www.ncbi.nlm.nih.gov/pubmed/19770473", "http://www.ncbi.nlm.nih.gov/pubmed/20954694", "http://www.ncbi.nlm.nih.gov/pubmed/20120204", "http://www.ncbi.nlm.nih.gov/pubmed/21054362", "http://www.ncbi.nlm.nih.gov/pubmed/17914062", "http://www.ncbi.nlm.nih.gov/pubmed/22816019", "http://www.ncbi.nlm.nih.gov/pubmed/19551474", "http://www.ncbi.nlm.nih.gov/pubmed/21070229", "http://www.ncbi.nlm.nih.gov/pubmed/22512641", "http://www.ncbi.nlm.nih.gov/pubmed/20826335", "http://www.ncbi.nlm.nih.gov/pubmed/18808506", "http://www.ncbi.nlm.nih.gov/pubmed/19036425", "http://www.ncbi.nlm.nih.gov/pubmed/22090312", "http://www.ncbi.nlm.nih.gov/pubmed/18590336", "http://www.ncbi.nlm.nih.gov/pubmed/21457238", "http://www.ncbi.nlm.nih.gov/pubmed/17929795", "http://www.ncbi.nlm.nih.gov/pubmed/19737844", "http://www.ncbi.nlm.nih.gov/pubmed/19914210", "http://www.ncbi.nlm.nih.gov/pubmed/19469188", "http://www.ncbi.nlm.nih.gov/pubmed/19779958", "http://www.ncbi.nlm.nih.gov/pubmed/20573757", "http://www.ncbi.nlm.nih.gov/pubmed/19219746", "http://www.ncbi.nlm.nih.gov/pubmed/19084002", "http://www.ncbi.nlm.nih.gov/pubmed/18039958", "http://www.ncbi.nlm.nih.gov/pubmed/20974601", "http://www.ncbi.nlm.nih.gov/pubmed/20188075", "http://www.ncbi.nlm.nih.gov/pubmed/20078608", "http://www.ncbi.nlm.nih.gov/pubmed/21221171", "http://www.ncbi.nlm.nih.gov/pubmed/25107879", "http://www.ncbi.nlm.nih.gov/pubmed/21383046", "http://www.ncbi.nlm.nih.gov/pubmed/19796656", "http://www.ncbi.nlm.nih.gov/pubmed/22278333", "http://www.ncbi.nlm.nih.gov/pubmed/20173082", "http://www.ncbi.nlm.nih.gov/pubmed/19579177", "http://www.ncbi.nlm.nih.gov/pubmed/20855369", "http://www.ncbi.nlm.nih.gov/pubmed/21631478", "http://www.ncbi.nlm.nih.gov/pubmed/18217201", "http://www.ncbi.nlm.nih.gov/pubmed/23798725", "http://www.ncbi.nlm.nih.gov/pubmed/20164785", "http://www.ncbi.nlm.nih.gov/pubmed/20433208", "http://www.ncbi.nlm.nih.gov/pubmed/19346171", "http://www.ncbi.nlm.nih.gov/pubmed/18991732", "http://www.ncbi.nlm.nih.gov/pubmed/20937606", "http://www.ncbi.nlm.nih.gov/pubmed/22221076" ]

[]

[]

[ "Photodynamic therapy was shown to have activity againt meningioma treatment. Gefitinib and ciprofloxacin enhance efficacy of photodynamic therapy." ]

[]

[ "CONCLUSIONS: Efficacy of 5-ALA PDT could be increased by adjunction of ciprofloxacin in conventional clinical dosing and by prolongation of ALA incubation time. ", "CONCLUSION: Gefitinib can inhibit ABCG2-mediated PpIX efflux from malignant brain tumor cells to increase the intracellular PpIX and thereby enhance the PDT effect.", "CONCLUSION: ALA-PDT was more effective in killing U-105MG glioma cells than CH-157MN meningioma cells.", "These data indicate unique features of AlPc which suggests its application as a potent, non-toxic photosensitizer in the photodynamic therapy of human meningiomas.", "Photodynamic therapy is being investigated as an adjuvant treatment for intracranial neoplasms. ", "It was found that PDT using haematoporphyrin derivative as a photosensitizing drug showed dose-dependent activity against a variety of histological subtypes of meningioma. ", "Photodynamic therapy is a promising treatment for human brain tumors because of the selective retention of certain compounds by tumor cells. ", "Susceptibility to 5-aminolevulinic acid based photodynamic therapy in WHO I meningioma cells corresponds to ferrochelatase activity.", "We conclude that differences in intracellular PpIX concentrations between HBL-52 and BEN-MEN-1 benign meningioma cells were mainly due to differences in FECH activity and that these differences correspond to their susceptibility to 5-ALA-induced PDT.", "Photodynamic therapy (PDT) has been employed in the management of recurrent cerebral gliomas but its activity against meningiomas has not been specifically studied.", "Enhancing the effect of 5-aminolevulinic acid based photodynamic therapy in human meningioma cells.", "An in vitro study of the effect of photodynamic therapy on human meningiomas.", "Photodynamic therapy (PDT) has been employed in the management of recurrent cerebral gliomas but its activity against meningiomas has not been specifically studied. " ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/8384325", "http://www.ncbi.nlm.nih.gov/pubmed/10327048", "http://www.ncbi.nlm.nih.gov/pubmed/23465372", "http://www.ncbi.nlm.nih.gov/pubmed/1984490", "http://www.ncbi.nlm.nih.gov/pubmed/8672259", "http://www.ncbi.nlm.nih.gov/pubmed/1388826", "http://www.ncbi.nlm.nih.gov/pubmed/2176016", "http://www.ncbi.nlm.nih.gov/pubmed/21073472", "http://www.ncbi.nlm.nih.gov/pubmed/16788926", "http://www.ncbi.nlm.nih.gov/pubmed/24486853", "http://www.ncbi.nlm.nih.gov/pubmed/2855780" ]

[]

[ "http://www.disease-ontology.org/api/metadata/DOID:3565", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D008579", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013812" ]

[ "Yes, it has been documented that implantation of carmustine wafers improves survival of newly diagnosed and recurrent glioblastoma patients." ]

[ "yes" ]

[ "At recurrence, treatment options include repeat surgery (with or without Gliadel wafer placement), reirradiation or systemic therapy. ", "DISCUSSION: Carmustine wafers for primary HGG surgery in accordance with the NICE TA121 were associated with a median survival of 15.3 months; this is improved compared with previously reported randomised trials. Multimodal treatment with carmustine wafers, radical radiotherapy and concomitant temozolomide was associated with improved survival.", "Gliadel wafer is a new approach to the treatment of glioblastoma, which involves controlled release delivery of carmustine from biodegradable polymer wafers. It has shown promising results and provides a silver lining for glioblastoma patients.", "For patient with and without Gliadel, median and 1-year RFS were 12.9 months and 52% vs. 14 months and 42%, respectively (p = 0.89).", "According to pathology, Gliadel did not influence OS of patients with Grade III or glioblastoma", "CONCLUSION: In patients with high-grade gliomas, adding Gliadel before performing a Stupp protocol did not improve survival.", "Randomized phase III trials have shown significant improvement of survival 1, 2, and 3 years after implantation of 1,3-bis (2-chloroethyl)-1-nitrosourea (BCNU) wafers for patients with newly diagnosed malignant glioma. ", "CONCLUSIONS: The combination of aggressive resection, Gliadel wafer implantation, and GKS in addition to standard fractionated RT in selected patients resulted in increased local control and increased survival compared with a historical control group treated with surgery and involved-field RT alone.", "OBJECT: Gliadel (BCNU) wafer and concomitant temozolomide (TMZ) therapy, when used individually as adjuvant therapies, extend survival from that achieved by resection and radiation therapy (XRT) for glioblastoma multiforme (GBM). ", "BACKGROUND: Gliadel (polifeprosan 20 with carmustine [BCNU] implant) is commonly used for local delivery of BCNU to high-grade gliomas after resection and is associated with increased survival.", "Temozolomide administered according to this protocol produced a median survival benefit of 2 months in glioblastomas, and carmustine a similar benefit in high-grade gliomas.", "Analysis of a large trial by Westphal and colleagues (n = 240) showed a 29% risk reduction (P = 0.03) in the BCNU wafer-treated group over the course of the 30-month trial.", "Median survival of patients treated with BCNU wafers was 13.8 months vs 11.6 months in placebo-treated patients (P = 0.017) with a hazard ratio of 0.73 (P = 0.018), representing a 27% significant risk reduction. This survival advantage was maintained at 1, 2, and 3 years and was statistically significant (P = 0.01) at 3 years.", "CONCLUSION: Malignant glioma patients treated with BCNU wafers at the time of initial surgery in combination with radiation therapy demonstrated a survival advantage at 2 and 3 years follow-up compared with placebo.", "OBJECTIVE: Recently a randomized placebo-controlled phase III trial of biodegradable polymers containing carmustine has demonstrated a significant survival benefit for patients treated with local chemotherapy. ", "CONCLUSION: In this subgroup analysis of a phase III trial population both the clinical progression and radiological progression were significantly delayed in patients treated with local chemotherapy, resulting in an increased survival time.", "A previous placebo-controlled trial has shown that biodegradable 1,3-bis (2-chloroethyl)-1-nitrosourea (BCNU) wafers (Gliadel wafers) prolong survival in patients with recurrent glioblastoma multiforme. A previously completed phase 3 trial, also placebo controlled, in 32 patients with newly diagnosed malignant glioma also demonstrated a survival benefit in those patients treated with BCNU wafers.", "Median survival in the intent-to-treat group was 13.9 months for the BCNU wafer-treated group and 11.6 months for the placebo-treated group (log-rank P -value stratified by country = 0.03), with a 29% reduction in the risk of death in the treatment group. When adjusted for factors affecting survival, the treatment effect remained positive with a risk reduction of 28% ( P = 0.03). ", "Controlled release delivery of carmustine from biodegradable polymer wafers was approved as an adjunct to surgical resection in the treatment of recurrent glioblastoma multiforme after it was shown in clinical trials to be well tolerated and effective. ", "Clinical trials have demonstrated significant improvements in survival and quality of life for patients after complete tumour resection and BCNU wafer implantation.", "BCNU wafers are an effective means of increasing survival and quality of life in patients diagnosed with malignant glioma, and are a valuable addition to the overall multimodal treatment strategy for these tumours.", "CONCLUSIONS: Carmustine wafer with concurrent TMZ and radiation followed by rotational chemotherapy is a well tolerated, effective therapy, and has a survival benefit compared with radiation alone.", "Median overall survival in 14 studies of newly-diagnosed patients suggested a modest improvement versus resection followed by Stupp protocol or resection with BCNU wafers, with an acceptable and manageable safety profile.", "The efficacy of carmustine wafers for older patients with glioblastoma multiforme: prolonging survival.", "DISCUSSION: Older patients with GBM may benefit from carmustine wafers. The survival for older patients who received carmustine wafers is significantly longer than matched patients who did not receive carmustine wafers.", "For glioblastoma patients who received ≥90% resection in the BCNU wafer study, median survival increased for BCNU wafer versus placebo (14.5 versus 12.4 months, respectively; P = 0.02), but no survival increase was found for <90% resection (11.7 versus 10.6 months, respectively; P = 0.98).", "A wafer impregnated with carmustine, for use as an implant after surgical removal of recurrent GBM showed a prolongation in the median survival time of only 2 mo, from 20 to 28 wk in a study with a total of 222 patients. ", "No clear survival benefit associated with wafer implantation was identified.", "In three of the trials, patients with GBM who received carmustine wafers had significantly longer median survival than patients who did not receive wafers. ", "TMZ and carmustine (BCNU) biodegradable wafer (Gliadel) are the only adjuvant chemotherapies that have improved survival in randomised GB clinical trials . ", "The carmustine implant wafer was demonstrated to improve survival in blinded placebo-controlled trials in selected patients with newly diagnosed or recurrent malignant glioma, with little increased risk of adverse events. ", "For patients undergoing repeat resection for malignant glioma, a randomized, blinded, placebo-controlled trial demonstrated a median survival for 110 patients who received carmustine polymers of 31 weeks compared with 23 weeks for 122 patients who only received placebo polymers.", "Median survival was improved from 11.6 to 13.9 months (P = 0.03), with a 29% reduction in the risk of death. When patients with glioblastoma multiforme alone were analyzed, the median survival improved from 11.4 to 13.5 months, but this improvement was not statistically significant. ", "OBJECT: Locoregional chemotherapy with carmustine wafers, positioned at surgery and followed by radiation therapy, has been shown to prolong survival in patients with newly diagnosed glioblastoma, as has concomitant radiochemotherapy with temozolomide.", "Following the resection of newly diagnosed or recurrent glioblastomas, local implantation of carmustine-impregnated biodegradable wafers (Gliadel) in the resection cavity constitutes an adjuvant therapy that can improve the possibilities of survival.", "The carmustine implant wafer was demonstrated to improve survival in blinded placebo-controlled trials in selected patients with newly diagnosed or recurrent malignant glioma, with little increased risk of adverse events.", "However, patients with carmustine wafers demonstrated prolonged survival as compared to patients without wafers.", "The median survival for patients with carmustine wafers was 8.7 months, while median survival for patients without wafers was 5.5 months (P=0.007).", "Likewise, in subgroup analysis, patients older than 70 years (P=0.0003) and 75 years (P=0.04) who had carmustine wafers had significantly longer survival than matched patients without wafers.", "Implantation of carmustine wafers did not significantly improve progression-free survival", "In three of the trials, patients with GBM who received carmustine wafers had significantly longer median survival than patients who did not receive wafers", "A previous placebo-controlled trial has shown that biodegradable 1,3-bis (2-chloroethyl)-1-nitrosourea (BCNU) wafers (Gliadel wafers) prolong survival in patients with recurrent glioblastoma multiforme", "A previously completed phase 3 trial, also placebo controlled, in 32 patients with newly diagnosed malignant glioma also demonstrated a survival benefit in those patients treated with BCNU wafers", "Following the resection of newly diagnosed or recurrent glioblastomas, local implantation of carmustine-impregnated biodegradable wafers (Gliadel) in the resection cavity constitutes an adjuvant therapy that can improve the possibilities of survival", "Multimodal treatment with carmustine wafers, radical radiotherapy and concomitant temozolomide was associated with improved survival", "The carmustine implant wafer was demonstrated to improve survival in blinded placebo-controlled trials in selected patients with newly diagnosed or recurrent malignant glioma, with little increased risk of adverse events", "TMZ and carmustine (BCNU) biodegradable wafer (Gliadel) are the only adjuvant chemotherapies that have improved survival in randomised GB clinical trials " ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/18366283", "http://www.ncbi.nlm.nih.gov/pubmed/23118709", "http://www.ncbi.nlm.nih.gov/pubmed/18240917", "http://www.ncbi.nlm.nih.gov/pubmed/15937647", "http://www.ncbi.nlm.nih.gov/pubmed/21983866", "http://www.ncbi.nlm.nih.gov/pubmed/16482400", "http://www.ncbi.nlm.nih.gov/pubmed/25054300", "http://www.ncbi.nlm.nih.gov/pubmed/17938702", "http://www.ncbi.nlm.nih.gov/pubmed/21390826", "http://www.ncbi.nlm.nih.gov/pubmed/21344976", "http://www.ncbi.nlm.nih.gov/pubmed/23662801", "http://www.ncbi.nlm.nih.gov/pubmed/18035958", "http://www.ncbi.nlm.nih.gov/pubmed/12074689", "http://www.ncbi.nlm.nih.gov/pubmed/22715955", "http://www.ncbi.nlm.nih.gov/pubmed/12672279", "http://www.ncbi.nlm.nih.gov/pubmed/22718138", "http://www.ncbi.nlm.nih.gov/pubmed/21479583", "http://www.ncbi.nlm.nih.gov/pubmed/10414561", "http://www.ncbi.nlm.nih.gov/pubmed/17350791", "http://www.ncbi.nlm.nih.gov/pubmed/18636295", "http://www.ncbi.nlm.nih.gov/pubmed/21300471", "http://www.ncbi.nlm.nih.gov/pubmed/19123896", "http://www.ncbi.nlm.nih.gov/pubmed/15069758", "http://www.ncbi.nlm.nih.gov/pubmed/20155992", "http://www.ncbi.nlm.nih.gov/pubmed/23535992", "http://www.ncbi.nlm.nih.gov/pubmed/17334672", "http://www.ncbi.nlm.nih.gov/pubmed/19046047", "http://www.ncbi.nlm.nih.gov/pubmed/23350777", "http://www.ncbi.nlm.nih.gov/pubmed/21330749", "http://www.ncbi.nlm.nih.gov/pubmed/25085219", "http://www.ncbi.nlm.nih.gov/pubmed/25269031", "http://www.ncbi.nlm.nih.gov/pubmed/21756557", "http://www.ncbi.nlm.nih.gov/pubmed/20706757", "http://www.ncbi.nlm.nih.gov/pubmed/20511192", "http://www.ncbi.nlm.nih.gov/pubmed/24246204", "http://www.ncbi.nlm.nih.gov/pubmed/19514083", "http://www.ncbi.nlm.nih.gov/pubmed/15015668" ]

[]

[ "http://www.biosemantics.org/jochem#4275776" ]

[ "Yes, Dicer is part of the RISC loading complex." ]

[ "yes" ]

[ "Dicer is a component of the protein machinery (the RNA Induced Silencing Complex [RISC]) which is involved in catalyzing the formation of mature microRNAs from their precursors in the process of microRNA biogenesis.", "RNA-induced silencing complex (RISC) Proteins PACT, TRBP, and Dicer are SRA binding nuclear receptor coregulators.", "The cytoplasmic RNA-induced silencing complex (RISC) contains dsRNA binding proteins, including protein kinase RNA activator (PACT), transactivation response RNA binding protein (TRBP), and Dicer, that process pre-microRNAs into mature microRNAs (miRNAs) that target specific mRNA species for regulation. ", " Although the major RNAi pathway proteins are found in most subcellular compartments, the miRNA- and siRNA-loaded Ago2 populations co-sediment almost exclusively with the rER membranes, together with the RISC loading complex (RLC) factors Dicer, TAR RNA binding protein (TRBP) and protein activator of the interferon-induced protein kinase (PACT).", "RNA interference (RNAi) is mediated by small interfering RNAs (siRNAs), which are liberated from double-stranded (ds)RNA precursors by Dicer and guide the RNA-induced silencing complex (RISC) to targets.", ". Dicer, an RNase III enzyme, plays a central role in the RNAi pathway by cleaving precursors of both of these classes of RNAs to form mature siRNAs and miRNAs, which are then loaded into the RNA-induced silencing complex (RISC). ", "Canonical siRNAs are 21 nucleotides (nt) in length and are loaded to the RNA Induced Silencing Complex when introduced into the cells, while longer siRNA molecules are first processed by endogenous Dicer and thus termed Dicer-substrate siRNA (DsiRNA). " ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/23511973", "http://www.ncbi.nlm.nih.gov/pubmed/23272173", "http://www.ncbi.nlm.nih.gov/pubmed/24303839", "http://www.ncbi.nlm.nih.gov/pubmed/23424633", "http://www.ncbi.nlm.nih.gov/pubmed/23550157", "http://www.ncbi.nlm.nih.gov/pubmed/23226452" ]

[ { "p": "http://linkedlifedata.com/resource/relationontology/hasLocalization", "s": "http://purl.uniprot.org/uniprot/A0MQH0", "o": "http://linkedlifedata.com/resource/geneontology/id/GO:0016442" }, { "p": "http://www.w3.org/2004/02/skos/core#prefLabel", "s": "http://linkedlifedata.com/resource/geneontology/id/GO:0016442", "o": "RNA-induced silencing complex" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_41304D5148300018", "o": "Endoribonuclease Dicer" }, { "p": "http://www.w3.org/2004/02/skos/core#altLabel", "s": "http://linkedlifedata.com/resource/geneontology/id/GO:0016442", "o": "RISC complex" }, { "p": "http://linkedlifedata.com/resource/relationontology/hasLocalization", "s": "http://purl.uniprot.org/uniprot/B3DLA6", "o": "http://linkedlifedata.com/resource/geneontology/id/GO:0016442" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_4233444C4136001C", "o": "Endoribonuclease Dicer" }, { "p": "http://linkedlifedata.com/resource/relationontology/hasLocalization", "s": "http://purl.uniprot.org/uniprot/Q25BN1", "o": "http://linkedlifedata.com/resource/geneontology/id/GO:0016442" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_513235424E310017", "o": "Endoribonuclease Dicer" }, { "p": "http://linkedlifedata.com/resource/relationontology/hasLocalization", "s": "http://purl.uniprot.org/uniprot/Q6TUI4", "o": "http://linkedlifedata.com/resource/geneontology/id/GO:0016442" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_5136545549340018", "o": "Endoribonuclease Dicer" }, { "p": "http://linkedlifedata.com/resource/relationontology/hasLocalization", "s": "http://purl.uniprot.org/uniprot/Q6TV19", "o": "http://linkedlifedata.com/resource/geneontology/id/GO:0016442" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_513654563139001C", "o": "Endoribonuclease Dicer" }, { "p": "http://purl.uniprot.org/core/classifiedWith", "s": "http://purl.uniprot.org/uniprot/A0MQH0", "o": "http://purl.uniprot.org/go/0016442" }, { "p": "http://www.w3.org/2004/02/skos/core#exactMatch", "s": "http://purl.uniprot.org/go/0016442", "o": "http://www.geneontology.org/go#GO:0016442" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://purl.uniprot.org/go/0016442", "o": "RISC complex" }, { "p": "http://www.w3.org/2000/01/rdf-schema#label", "s": "http://purl.uniprot.org/go/0016442", "o": "RNA-induced silencing complex" }, { "p": "http://purl.uniprot.org/core/classifiedWith", "s": "http://purl.uniprot.org/uniprot/B3DLA6", "o": "http://purl.uniprot.org/go/0016442" }, { "p": "http://purl.uniprot.org/core/classifiedWith", "s": "http://purl.uniprot.org/uniprot/Q25BN1", "o": "http://purl.uniprot.org/go/0016442" }, { "p": "http://purl.uniprot.org/core/classifiedWith", "s": "http://purl.uniprot.org/uniprot/Q6TUI4", "o": "http://purl.uniprot.org/go/0016442" }, { "p": "http://purl.uniprot.org/core/classifiedWith", "s": "http://purl.uniprot.org/uniprot/Q6TV19", "o": "http://purl.uniprot.org/go/0016442" } ]

[ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0016442", "http://www.uniprot.org/uniprot/DCR1_SCHPO", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0070578", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0070922", "http://www.uniprot.org/uniprot/DICER_CHICK", "http://www.uniprot.org/uniprot/DICER_HUMAN", "http://www.uniprot.org/uniprot/DICER_CRIGR", "http://www.uniprot.org/uniprot/DICER_MOUSE", "http://www.uniprot.org/uniprot/DICER_BOVIN", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D043244", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D034743" ]

[ "Arnold Chiari syndrome is a condition characterized by herniation of the cerebellar tonsils through the foramen magnum, manifesting usually with downbeat nystagmus, palsy of the caudal cerebral nerves, headache, and vertigo." ]

[]

[ "Arnold Chiari syndrome is a condition characterized by herniation of the cerebellar tonsils through the foramen magnum.", "The Arnold-Chiari malformation is very rare hindbrain abnormalities characterized by herniation of the hindbrain through the foramen magnum.", "The origin of Arnold-Chiari syndrome is connected with narrowness in the posterior fossa, particularly with narrowing of the arachnoid spaces.", "Arnold-Chiari Syndrome I is a malformation of the cervicomedullary junction, manifesting usually with downbeat nystagmus, palsy of the caudal cerebral nerves, headache, and vertigo." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/18546951", "http://www.ncbi.nlm.nih.gov/pubmed/19287845", "http://www.ncbi.nlm.nih.gov/pubmed/15785984", "http://www.ncbi.nlm.nih.gov/pubmed/17874345" ]

[]

[ "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=D001139", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013577" ]

[ "Recently, the impact of small ubiquitin-related modifier 1 (SUMO-1) on the regulation and preservation of sarcoplasmic reticulum calcium adenosine triphosphatase (SERCA2a) function was discovered. The small ubiquitin-related modifier (SUMO) can be conjugated to lysine residues of target proteins, and is involved in many cellular processes. SERCA2a is SUMOylated at lysines 480 and 585 and this SUMOylation is essential for preserving SERCA2a ATPase activity and stability in mouse and human cells. The levels of SUMO1 and the SUMOylation of SERCA2a itself were greatly reduced in failing hearts. SUMO-1 gene transfer improved cardiac function supporting the critical role of SUMO-1 in SERCA2a function and underlining the therapeutic potential of SUMO-1 for HF patients." ]

[]

[ "SERCA2a activity can be regulated at multiple levels of a signaling cascade comprised of phospholamban, protein phosphatase 1, inhibitor-1, and PKCα. SERCA2 activity is also regulated by post-translational modifications including SUMOylation and acetylation.", "The small ubiquitin-related modifier (SUMO) can be conjugated to lysine residues of target proteins, and is involved in many cellular processes. Here we show that SERCA2a is SUMOylated at lysines 480 and 585 and that this SUMOylation is essential for preserving SERCA2a ATPase activity and stability in mouse and human cells. The levels of SUMO1 and the SUMOylation of SERCA2a itself were greatly reduced in failing hearts.", "Taken together, our data show that SUMOylation is a critical post-translational modification that regulates SERCA2a function, and provide a platform for the design of novel therapeutic strategies for heart failure.", "Recently, the impact of small ubiquitin-related modifier 1 (SUMO-1) on the regulation and preservation of sarcoplasmic reticulum calcium adenosine triphosphatase (SERCA2a) function was discovered. The amount of myocardial SUMO-1 is decreased in failing hearts, and its knockdown results in severe heart failure (HF) in mice.", "SUMO-1 gene transfer therefore improved cardiac function and stabilized LV volumes in a large-animal model of HF. These results support the critical role of SUMO-1 in SERCA2a function and underline the therapeutic potential of SUMO-1 for HF patients.", "However, the initial simple view of a PLN/SERCA regulatory complex has been modified by our recent identification of SUMO, S100 and the histidine-rich Ca-binding protein as regulators of SERCA activity.", "The levels of SUMO1 and the SUMOylation of SERCA2a itself were greatly reduced in failing hearts", "Here we show that SERCA2a is SUMOylated at lysines 480 and 585 and that this SUMOylation is essential for preserving SERCA2a ATPase activity and stability in mouse and human cells", "Taken together, our data show that SUMOylation is a critical post-translational modification that regulates SERCA2a function, and provide a platform for the design of novel therapeutic strategies for heart failure", "SERCA2 activity is also regulated by post-translational modifications including SUMOylation and acetylation", "The levels of SUMO1 and the SUMOylation of SERCA2a itself were greatly reduced in failing hearts", "Here we show that SERCA2a is SUMOylated at lysines 480 and 585 and that this SUMOylation is essential for preserving SERCA2a ATPase activity and stability in mouse and human cells" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/23710633", "http://www.ncbi.nlm.nih.gov/pubmed/22679139", "http://www.ncbi.nlm.nih.gov/pubmed/24225946", "http://www.ncbi.nlm.nih.gov/pubmed/21900893" ]

[]

[ "http://www.uniprot.org/uniprot/AT2A2_RAT", "http://www.uniprot.org/uniprot/AT2A2_RABIT", "http://www.uniprot.org/uniprot/AT2A2_FELCA", "http://www.disease-ontology.org/api/metadata/DOID:6000", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0016925", "http://www.uniprot.org/uniprot/AT2A2_CHICK", "http://www.uniprot.org/uniprot/AT2A2_HUMAN", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0003301", "http://www.uniprot.org/uniprot/AT2A2_MOUSE", "http://www.uniprot.org/uniprot/AT2A2_PIG", "http://www.uniprot.org/uniprot/AT2A2_CANFA" ]

[ "At least six neudegenerative disorders result from trinucleotide repeat expansion: X-linked spinal and bulbar muscular atrophy (SBMA), two fragile X syndromes of mental retardation (FRAXA and FRAXE), Huntington's disease (HD), spinocerebellar ataxia type 1 (SCA1), and dentatorubral-pallidoluysian atrophy (DRPLA)." ]

[ "X-linked spinal and bulbar muscular atrophy (SBMA)", "Fragile X syndrome of mental retardation (FRAXA)", "Fragile X syndrome of mental retardation (FRAXE)", "Huntington's disease (HD)", "Spinocerebellar ataxia type 1 (SCA1)", "Dentatorubral-pallidoluysian atrophy (DRPLA)" ]

[ "The discovery that expansion of unstable repeats can cause a variety of neurological disorders has changed the landscape of disease-oriented research for several forms of mental retardation, Huntington disease, inherited ataxias, and muscular dystrophy.", "Expansion of trinucleotide repeats is now recognized as a major cause of neurological disease. At least seven disorders result from trinucleotide repeat expansion: X-linked spinal and bulbar muscular atrophy (SBMA), two fragile X syndromes of mental retardation (FRAXA and FRAXE), myotonic dystrophy, Huntington's disease, spinocerebellar ataxia type 1 (SCA1), and dentatorubral-pallidoluysian atrophy (DRPLA).", "Fragile X and myotonic dystrophy are multisystem disorders usually associated with large expansions of untranslated repeats, while the four neurodegenerative disorders, SBMA, Huntington's disease, SCA1, and DRPLA, are caused by smaller expansions of CAG repeats within the protein coding portion of the gene." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/17417937", "http://www.ncbi.nlm.nih.gov/pubmed/7998766" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D019680", "http://www.disease-ontology.org/api/metadata/DOID:863", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D002493", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0035753", "http://www.disease-ontology.org/api/metadata/DOID:331", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D018911", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009420", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009422" ]

[ "Yes, hypersensitivity to DNA crosslinking agents is one of the hallmarks of Fanconi anemia, the others being defective FANCD2 monoubiquitination, and genomic instability." ]

[ "yes" ]

[ "The Fanconi anemia (FA) core complex plays a central role in the DNA damage response network", "FAAP100-deficient cells display hallmark features of FA cells, including defective FANCD2 monoubiquitination, hypersensitivity to DNA crosslinking agents, and genomic instability.", "Fanconi anemia (FA) is a rare genetic disorder characterized by aplastic anemia, cancer/leukemia susceptibility and cellular hypersensitivity to DNA crosslinking agents, such as cisplatin.", "Fanconi anemia (FA) is an inherited chromosomal recessive syndrome characterized by cellular hypersensitivity to DNA crosslinking agents and bone marrow failure, which cause aplastic anemia, and an increased incidence of malignancy.", "Features of chromosomal aberrations, hypersensitivity to DNA crosslinking agents, and predisposition to malignancy have suggested a fundamental anomaly of DNA repair in Fanconi anemia.", "Fanconi anemia (FA) is one of several genetic diseases with characteristic cellular hypersensitivity to DNA crosslinking agents which suggest that FA proteins may function as part of DNA repair processes.", "Fanconi anemia (FA) is characterized by cellular hypersensitivity to DNA crosslinking agents, but how the Fanconi pathway protects cells from DNA crosslinks and whether FA proteins act directly on crosslinks remain unclear.", "Fanconi Anemia (FA) is a rare genetic disorder associated with a bone-marrow failure, cancer predisposition and hypersensitivity to DNA crosslinking agents.", "Fanconi anemia (FA) is a heterogeneous disease associated with a bone marrow failure, cancer predisposition and hypersensitivity to DNA crosslinking agents.", "Fanconi anemia (FA) is an inherited disorder characterized by defective DNA repair and cellular sensitivity to DNA crosslinking agents.", "Fanconi anemia (FA) is an inherited disease characterized by bone marrow failure, increased cancer risk and hypersensitivity to DNA cross-linking agents, implying a role for this pathway in the maintenance of genomic stability.", "Genetic or epigenetic inactivation of the pathway formed by the Fanconi Anemia (FA) proteins occurs in several cancer types, including head and neck squamous cell carcinomas (HNSCC), rendering the affected tumors potentially hypersensitive to DNA crosslinking agents.", "Fanconi Anemia (FA) is a rare autosomic recessive and X-linked disease with chromosomal instability after exposure to crosslinking agents as the hallmark.", "Fanconi Anemia (FA) is an autosomal recessive disease characterized by chromosome instability, cellular hypersensitivity to DNA cross-linking agents, and increased predisposition to malignancies.", "The Bloom protein (BLM) and Topoisomerase IIIalpha are found in association with proteins of the Fanconi anemia (FA) pathway, a disorder manifesting increased cellular sensitivity to DNA crosslinking agents.", "Using siRNA depletion and gene knockout techniques, we show that FAAP100-deficient cells display hallmark features of FA cells, including defective FANCD2 monoubiquitination, hypersensitivity to DNA crosslinking agents, and genomic instability.", "Fanconi anemia (FA) is a recessive human cancer prone syndrome featuring bone marrow failure, developmental abnormalities and hypersensitivity to DNA crosslinking agents exposure.", "FA is a chromosome instability syndrome characterized by childhood-onset aplastic anemia, cancer or leukemia susceptibility, and cellular hypersensitivity to DNA crosslinking agents.", "Functional defects in the Fanconi pathway can result in a marked hypersensitivity to interstrand crosslinking agents, such as mitomycin C.", "At the cellular level, hypersensitivity to DNA interstrand crosslinks is the defining feature in Fanconi anemia.", "DNA crosslinking agents may led to DNA cross-linking lesion, and Fanconi anemia pathway plays a key role in repairing its cross-linking.", "Fanconi anemia (FA), an autosomal recessive disorder of children, is characterized by congenital or childhood aplastic anemia, multiple developmental anomalies, increased incidence of myeloid leukemia, increased spontaneous chromosome breakage, and cellular and chromosomal hypersensitivity to DNA bifunctional crosslinking and alkylating agents.", "elegans provides an excellent model system for the study of the Fanconi Anemia (FA), one of the hallmarks of which is sensitivity to interstrand crosslinking agents", "Using siRNA depletion and gene knockout techniques, we show that FAAP100-deficient cells display hallmark features of FA cells, including defective FANCD2 monoubiquitination, hypersensitivity to DNA crosslinking agents, and genomic instability", "One of the hallmark phenotypes of FA is cellular hypersensitivity to agents that induce DNA interstrand crosslinks (ICLs), such as mitomycin C (MMC)", "Furthermore, the cytological hallmark of FA, the DNA crosslink-induced radial chromosome formation, exemplifies an innate impairment in the repair of these particularly cytotoxic DNA lesions [A.D", "Fanconi anemia (FA) is characterized by cellular hypersensitivity to DNA crosslinking agents, but how the Fanconi pathway protects cells from DNA crosslinks and whether FA proteins act directly on crosslinks remain unclear", "Features of chromosomal aberrations, hypersensitivity to DNA crosslinking agents, and predisposition to malignancy have suggested a fundamental anomaly of DNA repair in Fanconi anemia", "Fanconi anemia (FA) is an inherited chromosomal recessive syndrome characterized by cellular hypersensitivity to DNA crosslinking agents and bone marrow failure, which cause aplastic anemia, and an increased incidence of malignancy", "Genetic or epigenetic inactivation of the pathway formed by the Fanconi Anemia (FA) proteins occurs in several cancer types, including head and neck squamous cell carcinomas (HNSCC), rendering the affected tumors potentially hypersensitive to DNA crosslinking agents", "Fanconi anemia (FA) is a human autosomal disorder characterized by cancer susceptibility and cellular sensitivity to DNA crosslinking agents such as mitomycin C and diepoxybutane", "The Fanconi anemia pathway promotes DNA glycosylase-dependent excision of interstrand DNA crosslinks.", "DNA crosslinking agents may led to DNA cross-linking lesion, and Fanconi anemia pathway plays a key role in repairing its cross-linking", "FA is a chromosome instability syndrome characterized by childhood-onset aplastic anemia, cancer or leukemia susceptibility, and cellular hypersensitivity to DNA crosslinking agents", "The disease is manifested by defects in DNA repair, hypersensitivity to DNA crosslinking agents, and a high degree of chromosomal aberrations" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/16904272", "http://www.ncbi.nlm.nih.gov/pubmed/8058745", "http://www.ncbi.nlm.nih.gov/pubmed/19275569", "http://www.ncbi.nlm.nih.gov/pubmed/15277238", "http://www.ncbi.nlm.nih.gov/pubmed/18047734", "http://www.ncbi.nlm.nih.gov/pubmed/22690333", "http://www.ncbi.nlm.nih.gov/pubmed/10526221", "http://www.ncbi.nlm.nih.gov/pubmed/19101576", "http://www.ncbi.nlm.nih.gov/pubmed/21240275", "http://www.ncbi.nlm.nih.gov/pubmed/22053284", "http://www.ncbi.nlm.nih.gov/pubmed/21478198", "http://www.ncbi.nlm.nih.gov/pubmed/22532920", "http://www.ncbi.nlm.nih.gov/pubmed/20034732", "http://www.ncbi.nlm.nih.gov/pubmed/21109493", "http://www.ncbi.nlm.nih.gov/pubmed/25002988", "http://www.ncbi.nlm.nih.gov/pubmed/17396147", "http://www.ncbi.nlm.nih.gov/pubmed/19748364", "http://www.ncbi.nlm.nih.gov/pubmed/16493006", "http://www.ncbi.nlm.nih.gov/pubmed/23444773", "http://www.ncbi.nlm.nih.gov/pubmed/1809228", "http://www.ncbi.nlm.nih.gov/pubmed/19738377", "http://www.ncbi.nlm.nih.gov/pubmed/23318445", "http://www.ncbi.nlm.nih.gov/pubmed/20120016", "http://www.ncbi.nlm.nih.gov/pubmed/21939290" ]

[]

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

[ "The cellular targets of imatinib mesylate are BCR-ABL, platelet-derived growth factor receptor (PDGFR) and c-kit kinases." ]

[ "BCR-ABL", "Platelet-derived growth factor receptor (PDGFR)", "c-Kit" ]

[ "Imatinib mesylate is a tyrosine kinase inhibitor of the ABL, platelet-derived growth factor receptor (PDGFR), and c-kit kinases.", "Imatinib mesylate is a novel anti-tumor agent useful in the clinical management of chronic myelogenous leukemia and gastrointestinal stromal tumors with minimal toxicity relative to other forms of cancer therapy. Its clinical activity and minimal toxicity are related to specific inhibition of cellular targets including BCR-ABL, platelet-derived growth factor receptor and c-kit kinases, resulting in the collapse of downstream signaling cascades important for transformation." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/15887238", "http://www.ncbi.nlm.nih.gov/pubmed/15844661" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D017479", "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=D058990", "http://www.biosemantics.org/jochem#4275840", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D016503" ]

[ "The clinical characteristics of Tuberous Sclerosis include epilepsy, subependymal giant cell astrocytomas, lymphangioleiomyomatosis, rhabdomyoma, renal angiomyolipomas, cortical tubers, neurofibromas, angiofibromas, mental retardation, and behavioral disorders." ]

[ "epilepsy", "subependymal giant cell astrocytomas", "lymphangioleiomyomatosis", "rhabdomyoma", "renal angiomyolipomas", "cortical tubers", "neurofibromas", "angiofibromas", "mental retardation", "behavioral disorders" ]

[ "Prevalence and long-term outcome of epilepsy in tuberous sclerosis complex (TSC) is reported to be variable", "Subependymal giant cell astrocytomas (SEGAs) are benign tumors, most commonly associated with tuberous sclerosis complex (TSC).", "Lymphangioleiomyomatosis (LAM) is a rare, progressive, frequently lethal cystic lung disease that almost exclusively affects women.", "Rhabdomyoma is the most common type of cardiac tumor in fetuses and is often associated with tuberous sclerosis complex (TSC) with neurologic sequelae.", "In contrast to renal angiomyolipomas, which are often associated with tuberous sclerosis,", "clinical characteristics of subependymal nodule (SN) - subependymal giant cell astrocytoma (SGCA) complex in tuberous sclerosis", "NMI patients had a lower incidence of brain findings on imaging studies, neurological features, and renal findings than those with TSC2 mutations. In contrast, NMI patients had a lower incidence of seizures than TSC patients with TSC1 mutations, but had a higher incidence of both renal angiomyolipomas and pulmonary lymphangioleiomyomatosis.", "clinical characteristics of subjects with pulmonary lymphangioleiomyomatosis, both sporadic and tuberous sclerosis-related forms.", "Women with tuberous sclerosis-related lymphangioleiomyomatosis were younger and had less impaired lung function compared with those with the sporadic form.", "Balloon cells are histopathological hallmarks of various cortical malformations, i.e., focal cortical dysplasia (Taylor's type, FCD IIb), hemimegalencephaly (HME) or cortical tubers (tuberous sclerosis, TSC). ", "Pulmonary lymphangioleiomyomatosis is a rare cause of recurrent pneumothorax and should be considered a differential diagnosis, especially in young women with diffuse bilateral bullous emphysema or tuberous sclerosis.", "The disease is characterized by the development of benign hamartomatous tumors: neurofibromas and angiofibromas, located in the skin, central nervous system, mucosas and other organs. Abnormal neural cell migration plays an important role in the neurological dysfunctions found in TS, the predominant features being mental retardation, seizures and behavioral disorders.", "The true prevalence of pulmonary lymphangioleiomyomatosis (LAM) in patients with tuberous sclerosis complex (TSC) is unknown.", "We retrospectively reviewed a cohort of patients with TSC and refractory epilepsy who started CLB over a 5-year period. Clinical characteristics and number of tubers on MRI were assessed." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/14716484", "http://www.ncbi.nlm.nih.gov/pubmed/22791573", "http://www.ncbi.nlm.nih.gov/pubmed/19889303", "http://www.ncbi.nlm.nih.gov/pubmed/16210669", "http://www.ncbi.nlm.nih.gov/pubmed/23219029", "http://www.ncbi.nlm.nih.gov/pubmed/23007140", "http://www.ncbi.nlm.nih.gov/pubmed/19133941", "http://www.ncbi.nlm.nih.gov/pubmed/24304436", "http://www.ncbi.nlm.nih.gov/pubmed/15221338", "http://www.ncbi.nlm.nih.gov/pubmed/19239998", "http://www.ncbi.nlm.nih.gov/pubmed/24180681", "http://www.ncbi.nlm.nih.gov/pubmed/12618672", "http://www.ncbi.nlm.nih.gov/pubmed/11520735" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012640", "http://www.uniprot.org/uniprot/TSC2_RAT", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0033596", "http://www.uniprot.org/uniprot/TSC1_RAT", "http://www.disease-ontology.org/api/metadata/DOID:13515", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D014402", "http://www.uniprot.org/uniprot/TSC2_MOUSE", "http://www.disease-ontology.org/api/metadata/DOID:557", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D007674", "http://www.uniprot.org/uniprot/TSC1_SCHPO", "http://www.uniprot.org/uniprot/TSC1_HUMAN", "http://www.disease-ontology.org/api/metadata/DOID:850", "http://www.uniprot.org/uniprot/TSC2_SCHPO", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D008171", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D008607", "http://www.biosemantics.org/jochem#4266396", "http://www.uniprot.org/uniprot/TSC1_MOUSE", "http://www.disease-ontology.org/api/metadata/DOID:1059", "http://www.uniprot.org/uniprot/TSC2_HUMAN" ]

[ "We report eleven new families of MEdium Reiteration frequency (MER) interspersed repeats in the genomes of Primates, Rodentia, and Lagomorpha. Two families of the human repeats, MER 46 and MER 47, represent non-autonomous DNA transposons. These sequences are flanked by TA target site duplications and have terminal inverted repeats (TIRs) similar to TIRs of DNA transposons. The sequences of five other families of repeats, MER41, MER48, MER50, MER51, and RMER3, resemble long terminal repeats of retroviruses. A potential involvement of some of the reported MER repeats in the regulation of transcription and genetic rearrangements is suggested. Age estimations place the origin of most MER repeats at the time of decline in MIR (Mammalian-wide Interspersed Repeats) retroposition and before the origin of the Alu familyMER41 repeat sequences contain inducible STAT1 binding sites", "The sequences of five families of repeats, MER41, MER48, MER50, MER51, and RMER3, resemble long terminal repeats of retroviruses. Age estimations place the origin of most MER repeats at the time of decline in MIR (Mammalian-wide Interspersed Repeats) retroposition and before the origin of the Alu family. MER41 repeat sequences contain inducible STAT1 binding sites. The observation of the binding of activated STAT1 protein to a specific repetitive element bolsters similar reports concerning p53 and other TFs, and strengthens the notion of an involvement of repeats in gene regulation.", "We report eleven new families of MEdium Reiteration frequency (MER) interspersed repeats in the genomes of Primates, Rodentia, and Lagomorpha. Two families of the human repeats, MER 46 and MER 47, represent non-autonomous DNA transposons. These sequences are flanked by TA target site duplications and have terminal inverted repeats (TIRs) similar to TIRs of DNA transposons. The sequences of five other families of repeats, MER41, MER48, MER50, MER51, and RMER3, resemble long terminal repeats of retroviruses. A potential involvement of some of the reported MER repeats in the regulation of transcription and genetic rearrangements is suggested. Age estimations place the origin of most MER repeats at the time of decline in MIR (Mammalian-wide Interspersed Repeats) retroposition and before the origin of the Alu family MER41 repeat sequences contain inducible STAT1 binding sites " ]

[]

[ "We report eleven new families of MEdium Reiteration frequency (MER) interspersed repeats in the genomes of Primates, Rodentia, and Lagomorpha. Two families of the human repeats, MER 46 and MER 47, represent non-autonomous DNA transposons. These sequences are flanked by TA target site duplications and have terminal inverted repeats (TIRs) similar to TIRs of DNA transposons. The sequences of five other families of repeats, MER41, MER48, MER50, MER51, and RMER3, resemble long terminal repeats of retroviruses. A potential involvement of some of the reported MER repeats in the regulation of transcription and genetic rearrangements is suggested. Age estimations place the origin of most MER repeats at the time of decline in MIR (Mammalian-wide Interspersed Repeats) retroposition and before the origin of the Alu family", "MER41 repeat sequences contain inducible STAT1 binding sites", "Contrary to previous claims, we find no evidence that STAT1 binds to multiple distinct motifs upon interferon-gamma stimulation in vivo. While a large majority of genomic sites with high ChIP-seq signal is associated with a nucleotide sequence resembling a STAT1 binding site, only a very small subset of the over 5 million potential STAT1 binding sites in the human genome is covered by ChIP-seq data. Furthermore a surprisingly large fraction of the ChIP-seq signal (5%) is absorbed by a small family of repetitive sequences (MER41). The observation of the binding of activated STAT1 protein to a specific repetitive element bolsters similar reports concerning p53 and other TFs, and strengthens the notion of an involvement of repeats in gene regulation. Incidentally MER41 are specific to primates, consequently, regulatory mechanisms in the IFN-STAT pathway might fundamentally differ between primates and rodents. On a methodological aspect, the presence of large numbers of nearly identical binding sites in repetitive sequences may lead to wrong conclusions about intrinsic binding preferences of TF as illustrated by the spacing analysis STAT1 tandem motifs. Therefore, ChIP-seq data should be analyzed independently within repetitive and non-repetitive sequences", "MER41 repeat sequences contain inducible STAT1 binding sites.", "The sequences of five other families of repeats, MER41, MER48, MER50, MER51, and RMER3, resemble long terminal repeats of retroviruses.", "Furthermore a surprisingly large fraction of the ChIP-seq signal (5%) is absorbed by a small family of repetitive sequences (MER41).", "Incidentally MER41 are specific to primates, consequently, regulatory mechanisms in the IFN-STAT pathway might fundamentally differ between primates and rodents.", "The sequences of five other families of repeats, MER41, MER48, MER50, MER51, and RMER3, resemble long terminal repeats of retroviruses.", "Furthermore a surprisingly large fraction of the ChIP-seq signal (5%) is absorbed by a small family of repetitive sequences (MER41).", "Incidentally MER41 are specific to primates, consequently, regulatory mechanisms in the IFN-STAT pathway might fundamentally differ between primates and rodents.", "The sequences of five other families of repeats, MER41, MER48, MER50, MER51, and RMER3, resemble long terminal repeats of retroviruses", "Furthermore a surprisingly large fraction of the ChIP-seq signal (5%) is absorbed by a small family of repetitive sequences (MER41)", "Incidentally MER41 are specific to primates, consequently, regulatory mechanisms in the IFN-STAT pathway might fundamentally differ between primates and rodents" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/20625510", "http://www.ncbi.nlm.nih.gov/pubmed/9204548" ]

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[ "Functional connectivity in the default mode network (DMN) is reduced in patients with different disorders of consciousness, and correlates with the level of consciousness. \nSpecifically, functional connectivity in the default mode network was shown to be absent in brain death patients, extremely low in vegetative state patients and slightly decreased in minimally conscious state patients when compared to healthy subjects. Therefore, functional connectivity in the default mode network was suggested to be valuable in differentiating patients with different disorders of consciousness. Clinically, functional connectivity in the default mode network was also shown to be an indicator of the extent of cortical disruption and predict reversible impairments in consciousness." ]

[]

[ "Functional connectivity in the default mode network (DMN) is known to be reduced in patients with disorders of consciousness, to a different extent depending on their clinical severity.", "Patients showed significant impairments in all of the pathways connecting cortical regions within this network, as well as the pathway connecting the posterior cingulate cortex/precuneus with the thalamus, relative to the healthy volunteers.", "Moreover, the structural integrity of this pathway, as well as that of those connecting the posterior areas of the network, was correlated with the patients' behavioral signs for awareness, being higher in EMCS patients than those in the upper and lower ranges of the MCS patients, and lowest in VS patients.", "These results provide a possible neural substrate for the functional disconnection previously described in these patients, and reinforce the importance of the DMN in the genesis of awareness and the neural bases of its disorders.", "Although the functional significance of the default-mode network remains a matter of debate, it has been suggested to be a candidate for the network subserving basic functions related to consciousness.", "Despite resolution of corpus callosum lesion on magnetic resonance imaging (MRI) within 1 week, the patient persistently presented disturbance of consciousness. Resting-state functional MRI revealed that the posterior cingulate cortex/precuneus was functionally disconnected from other brain regions within the default-mode network.", "Our case report suggests that assessment of the functional connectivity in the resting-state default-mode network could be a useful marker of consciousness disturbance even in the presence of a reversible brain lesion.", "A present and intact DMN was observed in controls and those patients who subsequently regained consciousness, but was disrupted in all patients who failed to regain consciousness.", "The results suggest that the DMN is necessary but not sufficient to support consciousness.", "Clinically, DMN connectivity may serve as an indicator of the extent of cortical disruption and predict reversible impairments in consciousness.", "Recent studies on resting state activity in DOC, measured with functional magnetic resonance imaging (fMRI) techniques, show that functional connectivity is disrupted in the task-negative or the default mode network.", "This report shows for the first time, in three patients, that the persistent vegetative state (PVS) is marked by a dysfunctional default mode network, with decreased connectivity in several brain regions, including the dorsolateral prefrontal cortex and anterior cingulated cortex, especially in the right hemisphere." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/23034909", "http://www.ncbi.nlm.nih.gov/pubmed/22418054", "http://www.ncbi.nlm.nih.gov/pubmed/22905075", "http://www.ncbi.nlm.nih.gov/pubmed/22623966", "http://www.ncbi.nlm.nih.gov/pubmed/21693087", "http://www.ncbi.nlm.nih.gov/pubmed/21191476", "http://www.ncbi.nlm.nih.gov/pubmed/22218274", "http://www.ncbi.nlm.nih.gov/pubmed/19289479", "http://www.ncbi.nlm.nih.gov/pubmed/22039473", "http://www.ncbi.nlm.nih.gov/pubmed/22563263" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D059907", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009415", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D003244" ]

[ "Novel C12orf65 mutations in patients with axonal neuropathy and optic atrophy", "The association of neuropathy and optic atrophy (also known as Charcot-Marie-Tooth [CMT] disease type 6) has been described with autosomal dominant, recessive and X-linked modes of inheritance. Mutations in Mitofusin 2 have been found to cause dominant forms of CMT6. Phosphoribosylpyrophosphate synthetase-I mutations cause X-linked CMT6, whereas a protein-truncating mutation in the C12orf65 gene, which codes for a protein involved in mitochondrial translation, was found to be the cause of an autosomal recessive form of the disease, with childhood onset neuropathy and optic atrophy." ]

[ "yes" ]

[ "Novel C12orf65 mutations in patients with axonal neuropathy and optic atrophy", "Charcot-Marie Tooth disease (CMT) forms a clinically and genetically heterogeneous group of disorders. Although a number of disease genes have been identified for CMT, the gene discovery for some complex form of CMT has lagged behind. The association of neuropathy and optic atrophy (also known as CMT type 6) has been described with autosomaldominant, recessive and X-linked modes of inheritance. Mutations in Mitofusin 2 have been found to cause dominant forms of CMT6. Phosphoribosylpyrophosphate synthetase-I mutations cause X-linked CMT6, but until now, mutations in the recessive forms of disease have never been identified.METHODS: We here describe a family with three affected individuals who inherited in an autosomal recessive fashion a childhood onset neuropathy and optic atrophy. Using homozygosity mapping in the family and exome sequencing in two affected individuals we identified a novel protein-truncating mutation in the C12orf65 gene, which encodes for a protein involved in mitochondrial translation", "Novel C12orf65 mutations in patients with axonal neuropathy and optic atrophy.", "Our study broadens the phenotypic spectrum of C12orf65 defects and highlights the triad of optic atrophy, axonal neuropathy and spastic paraparesis as its key clinical features.", "C12orf65 participates in the process of mitochondrial translation and has been shown to be associated with a spectrum of phenotypes, including early onset optic atrophy, progressive encephalomyopathy, peripheral neuropathy, and spastic paraparesis.We used whole-genome homozygosity mapping as well as exome sequencing and targeted gene sequencing to identify novel C12orf65 disease-causing mutations in seven affected individuals originating from two consanguineous families.", "A homozygous mutation of C12orf65 causes spastic paraplegia with optic atrophy and neuropathy (SPG55).", "Optic atrophy and a Leigh-like syndrome due to mutations in the c12orf65 gene: report of a novel mutation and review of the literature.", "Recently, we identified the causative gene, C12orf65, that was reported the gene for Leigh syndrome, for autosomal recessive spastic paraplegia with optic atrophy and neuropathy (SPG55).", "We describe 2 siblings with compound heterozygous mutations in the recently identified C12orf65 gene who presented with optic atrophy and mild developmental delays and subsequently developed bilateral, symmetric lesions in the brainstem reminiscent of Leigh syndrome.", "C12orf65 participates in the process of mitochondrial translation and has been shown to be associated with a spectrum of phenotypes, including early onset optic atrophy, progressive encephalomyopathy, peripheral neuropathy, and spastic paraparesis.We used whole-genome homozygosity mapping as well as exome sequencing and targeted gene sequencing to identify novel C12orf65 disease-causing mutations in seven affected individuals originating from two consanguineous families", "Our study broadens the phenotypic spectrum of C12orf65 defects and highlights the triad of optic atrophy, axonal neuropathy and spastic paraparesis as its key clinical features", "CONCLUSIONS: This work describes a mutation in the C12orf65 gene that causes recessive form of CMT6 and confirms the role of mitochondrial dysfunction in this complex axonal neuropathy.", "C12orf65 participates in the process of mitochondrial translation and has been shown to be associated with a spectrum of phenotypes, including early onset optic atrophy, progressive encephalomyopathy, peripheral neuropathy, and spastic paraparesis.We used whole-genome homozygosity mapping as well as exome sequencing and targeted gene sequencing to identify novel C12orf65 disease-causing mutations in seven affected individuals originating from two consanguineous families. ", "Our study broadens the phenotypic spectrum of C12orf65 defects and highlights the triad of optic atrophy, axonal neuropathy and spastic paraparesis as its key clinical features. ", "We described a large consanguineous family with neuropathy and optic atrophy carrying a loss of function mutation in the C12orf65 gene.", "In these patients, we identified a homozygous splice mutation, g.21043 T>A (c.282+2 T>A) which leads to skipping of exon 2. Our study broadens the phenotypic spectrum of C12orf65 defects and highlights the triad of optic atrophy, axonal neuropathy and spastic paraparesis as its key clinical features.", "This work describes a mutation in the C12orf65 gene that causes recessive form of CMT6 and confirms the role of mitochondrial dysfunction in this complex axonal neuropathy.", "Our study broadens the phenotypic spectrum of C12orf65 defects and highlights the triad of optic atrophy, axonal neuropathy and spastic paraparesis as its key clinical features.", "Novel C12orf65 mutations in patients with axonal neuropathy and optic atrophy.", "This work describes a mutation in the C12orf65 gene that causes recessive form of CMT6 and confirms the role of mitochondrial dysfunction in this complex axonal neuropathy.", "A homozygous mutation of C12orf65 causes spastic paraplegia with optic atrophy and neuropathy (SPG55).", "C12orf65 participates in the process of mitochondrial translation and has been shown to be associated with a spectrum of phenotypes, including early onset optic atrophy, progressive encephalomyopathy, peripheral neuropathy, and spastic paraparesis.We used whole-genome homozygosity mapping as well as exome sequencing and targeted gene sequencing to identify novel C12orf65 disease-causing mutations in seven affected individuals originating from two consanguineous families." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/24198383", "http://www.ncbi.nlm.nih.gov/pubmed/24424123", "http://www.ncbi.nlm.nih.gov/pubmed/25519961", "http://www.ncbi.nlm.nih.gov/pubmed/24284555", "http://www.ncbi.nlm.nih.gov/pubmed/23188110" ]

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[ "Dexamethasone (a steroid hormone), cytarabine (ara-C), cisplatin (platinum agent) and rituximab are included in the DHAP-R chemotherapy protocol." ]

[ "dexamethasone", "cytarabine", "cisplatin", "rituximab" ]

[ "Standard treatment of transplant-eligible patients with relapsed diffuse large B-cell lymphoma (DLBCL) consists of rituximab and platinum-based chemotherapy, either ifosfamide, carboplatin, and etoposide (ICE) or dexamethasone, cytarabine, and cisplatin (DHAP), with autologous transplant consolidation for those with chemosensitive disease.", "The intergroup Collaborative Trial in Relapsed Aggressive Lymphoma (CORAL) set the limits for this standard of treatment after first comparing 2 salvage regimens: rituximab, ifosfamide, etoposide, and carboplatin (R-ICE) and rituximab, dexamethasone, aracytine, and cisplatin (R-DHAP). ", "The response rate (RR) to first salvage chemotherapy was 23% (RR by regimen: dexamethasone, cytosine arabinoside and cisplatin [DHAP] 15%, etoposide, Solu-Medrol, cytosine arabinoside and cisplatin [ESHAP] 36%, and gemcitabine, dexamethasone and cisplatin [GDP] 45%); 25% (n = 28) of patients underwent ASCT. ", "PURPOSE: To evaluate the prognostic value of the cell of origin (COO) in patients with relapsed/refractory diffuse large B-cell lymphoma (DLBLC), prospectively treated by rituximab, dexamethasone, high-dose cytarabine, and cisplatin (R-DHAP) versus rituximab, ifosfamide, carboplatin, and etoposide and followed by intensive therapy plus autologous stem-cell transplantation on the Collaborative Trial in Relapsed Aggressive Lymphoma (CORAL) trial. ", "The aim of this study was to evaluate the efficacy and toxicity of two chemotherapy regimens based on platinum and cytarabine in association with etoposide and methylprednisolone (ESHAP) or with dexamethasone (DHAP) with or without Rituximab (± R) in patients with refractory or a relapsed Primary Central Nervous System Lymphoma (PCNSL). ", "R-DHAP combines rituximab with cisplatin, cytarabine, and dexamethasone. ", "PATIENTS AND METHODS: Patients with CD20(+) DLBCL in first relapse or who were refractory after first-line therapy were randomly assigned to either rituximab, ifosfamide, etoposide, and carboplatin (R-ICE) or rituximab, dexamethasone, high-dose cytarabine, and cisplatin (R-DHAP).", "Because of the inability to safely administer unattenuated doses of anthracycline-based regimens, dexamethasone, high-dose cytarabine, and cisplatin (DHAP) was used at full doses (along with rituximab for the DLBCL patient) until hepatic function normalized (1-5 cycles). ", "Randomized to DHAP (cisplatin-cytarabine-dexamethasone)-VIM (etoposide-ifosfamide-methotrexate)-DHAP (cisplatin-cytarabine-dexamethasone) chemotherapy with rituximab (R; R-DHAP arm) were 119 patients (113 evaluable) and to chemotherapy without rituximab (DHAP arm) 120 patients (112 evaluable). ", "Patients are first randomised between ICE (ifosfamide, carboplatin, etoposide) and DHAP (dexamethasone, ara-C and cisplatin), both combined with rituximab (R-ICE or R-DHAP).", "BACKGROUND AND OBJECTIVE: The treatment of the patients with relapsed and refractory non-Hodgkin's lymphoma(NHL) remains difficult. It was reported that DHAP regimen(cisplatin + Ara-C + dexamthsone) was an effective salvage therapy, but there was no report about it in China. ", "Randomized to DHAP (cisplatin-cytarabine-dexamethasone)-VIM (etoposide-ifosfamide-methotrexate)-DHAP (cisplatin-cytarabine-dexamethasone) chemotherapy with rituximab (R; R-DHAP arm) were 119 patients (113 evaluable) and to chemotherapy without rituximab (DHAP arm) 120 patients (112 evaluable).", "Randomized to DHAP (cisplatin-cytarabine-dexamethasone)-VIM (etoposide-ifosfamide-methotrexate)-DHAP (cisplatin-cytarabine-dexamethasone) chemotherapy with rituximab (R; R-DHAP arm) were 119 patients (113 evaluable) and to chemotherapy without rituximab (DHAP arm) 120 patients (112 evaluable)" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/22136378", "http://www.ncbi.nlm.nih.gov/pubmed/20709662", "http://www.ncbi.nlm.nih.gov/pubmed/21947824", "http://www.ncbi.nlm.nih.gov/pubmed/19406729", "http://www.ncbi.nlm.nih.gov/pubmed/12478903", "http://www.ncbi.nlm.nih.gov/pubmed/23692856", "http://www.ncbi.nlm.nih.gov/pubmed/20660832", "http://www.ncbi.nlm.nih.gov/pubmed/23233612", "http://www.ncbi.nlm.nih.gov/pubmed/16702182", "http://www.ncbi.nlm.nih.gov/pubmed/21656329", "http://www.ncbi.nlm.nih.gov/pubmed/17971487" ]

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[ "Yes, psammoma bodies are commonly seen and are characteristic to meningiomas. However, they can be also present in other types of tumors or non-neoplastic tissues." ]

[ "yes" ]

[ "Psammoma bodies (PBs) are concentric lamellated calcified structures, observed most commonly in papillary thyroid carcinoma (PTC), meningioma, and papillary serous cystadenocarcinoma of ovary but have rarely been reported in other neoplasms and nonneoplastic lesions.", "Studies on serous cystadenocarcinoma of ovary and meningioma, however, revealed that collagen production by neoplastic cells and subsequent calcification was responsible for the formation of PBs.", "The existence of some precursor forms of PBs was reported in meningiomas and more recently in PTC, which were mostly in the form of extracellular hyaline globules surrounded by well-preserved neoplastic cells or in a smaller number of cases intracytoplasmic bodies liberated from intact tumor cells.", "Light microscopy revealed abundant microcysts of varied size throughout the tumor tissue with the presence of whorl formation and psammoma body, but no malignancy was indicated. Electron microscopy further demonstrated interdigitation of the neighboring cell membranes, desmosomes, and intracytoplasmic filaments, which are pathognomonic findings of meningiomas.", "Unlike SFT, FMs were glycogen-containing and variously exhibited a storiform pattern (13 of 20), psammoma body formation (9 of 20), and calcification of collagen (4 of 20). Immunoreactivities included vimentin (100%), focal to patchy EMA (80%), S-100 protein (80%), collagen IV (25%), and patchy, mild-to-moderate CD34 staining (60%).", "In contrast to the inner structure, three-dimensional structure of psammona bodies in meningiomas is not well defined.", "This study examined three cultured meningiomas, in which surface observation of psammoma bodies might be easier than in the tumor tissues since influence of interposing connective tissue is minimized in tissue culture.", "The results suggest that psammoma bodies in meningiomas arise in part from meningothelial whorls due to collagen production by tumor cells followed by obliteration and disappearance of tumor cell processes, although some of the alternative pathways for psammoma body formation proposed by other investigators cannot be ruled out by this study.", "To demonstrate that psammoma bodies in human meningiomas contain type VI collagen and laminin.", "This is the first report to describe the involvement of type VI collagen in psammoma bodies and whorl formations in meningiomas.", "Calcification such as psammoma body is sometimes found especially in spinal cord meningioma but ossification of the meningeal tumor was rarely observed.", "Histological diagnosis was transitional meningioma with psammoma body.", "In this study we analyzed the morphologic and ultrastructural characteristics of the psammoma bodies in ten meningiomas of different histologic subtypes, characterizing the components of the psammoma body and the elements of the tumor, such as the capillaries and degenerative cells that have been classically considered as initiators of the formation of these calcareous is structures.", "It is concluded that the mineralization of the psammoma bodies is induced principally by the collagen fibers synthesized by the meningocytes and that the form of mineralization is spherical and growth is radial, controlled by the tumoral cells.", "CSF cytology revealed benign fibroblastic or meningotheliomatous meningioma with whorl formation and psammoma body.", "Electron microscopic examination of the calculi showed membrane-bound vesicles and radially precipitated crystals that simulated hydroxyapatite of psammoma body in meningioma.", "Psammoma bodies in meningiomas resembled those in the choroid plexus stroma.", "The results of this study suggest that psammoma bodies in the choroid plexus, as in meningiomas, form by a process of dystrophic calcification associated with arachnoid cells and collagen fibres.", "An early stage of psammoma body formation was seen more frequently in these villous microcores than in the meningocytic whorls.", "Psammoma bodies in meningocytic whorls were investigated by electron microscopy.", "Psammoma body formation in the meningocytic whorls may represent degeneration in some whorls of the central cells which contain connective tissue fibers, producing cell debris such as membrane invested vesicles.", "Twenty human meningiomas were examined for IgG and IgM by the direct immunofluorescence of immunoperoxidase methods, or both. IgG was conspicuously found in and around the blood vessels, whorls, and psammoma bodies. It was also clearly present on the cytoplasmic membranes of the tumour cells.", "Significance of these findings is briefly discussed including possible humoral immune reactions in regard to whorl and psammoma body formation in meningioma.", "The fine structure of psammoma bodies was examined in four cases of fibroblastic meningioma.", "In general, large numbers of various-sized calcified bodies (psammoma bodies) were scattered among the interstitial fibers.", "These findings suggest that both matrix giant bodies and matrix vesicles may serve as initial nidus of calcification of psammoma bodies in fibroblastic meningioma.", "Psammoma body formation or dystrophic mineralization and gliosis of the intervening parenchyma was observed in all three cases." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/2168257", "http://www.ncbi.nlm.nih.gov/pubmed/8162148", "http://www.ncbi.nlm.nih.gov/pubmed/3020860", "http://www.ncbi.nlm.nih.gov/pubmed/8336812", "http://www.ncbi.nlm.nih.gov/pubmed/3776472", "http://www.ncbi.nlm.nih.gov/pubmed/8712177", "http://www.ncbi.nlm.nih.gov/pubmed/8629394", "http://www.ncbi.nlm.nih.gov/pubmed/19373908", "http://www.ncbi.nlm.nih.gov/pubmed/1492779", "http://www.ncbi.nlm.nih.gov/pubmed/3736772", "http://www.ncbi.nlm.nih.gov/pubmed/7487408", "http://www.ncbi.nlm.nih.gov/pubmed/7015802", "http://www.ncbi.nlm.nih.gov/pubmed/10396741", "http://www.ncbi.nlm.nih.gov/pubmed/8727067", "http://www.ncbi.nlm.nih.gov/pubmed/6699695", "http://www.ncbi.nlm.nih.gov/pubmed/1630573" ]

[]

[ "http://www.disease-ontology.org/api/metadata/DOID:7210", "http://www.disease-ontology.org/api/metadata/DOID:3565", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D002479", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D008579" ]

[ "Lambert-Eaton myasthenic syndrome is a neuromuscular junction disorder characterized by proximal limb muscle weakness, fatigability, decreased deep-tendon reflexes, and autonomic symptoms. There are 2 forms of Lambert-Eaton myasthenic syndrome: one most frequently associated with small-cell lung cancer (P-Lambert-Eaton myasthenic syndrome) and the other that is a pure autoimmune form (NP-Lambert-Eaton myasthenic syndrome)", "Lambert-Eaton myasthenic syndrome is a neuromuscular junction disorder characterized by proximal limb muscle weakness, fatigability, decreased deep-tendon reflexes, and autonomic symptoms, that may include dry mouth, constipation, blurred vision, impaired sweating, and orthostatic hypotension. There are 2 forms of Lambert-Eaton myasthenic syndrome: one most frequently associated with small-cell lung cancer, and the other that is a pure autoimmune form." ]

[ "proximal limb muscle weakness", "fatigability", "decreased deep-tendon reflexes", "autonomic symptoms", "small-cell lung cancer" ]

[ "Lambert-Eaton myasthenic syndrome is a neuromuscular junction disorder characterized by proximal limb muscle weakness, fatigability, decreased deep-tendon reflexes, and autonomic symptoms. There are 2 forms of Lambert-Eaton myasthenic syndrome: one most frequently associated with small-cell lung cancer (P-Lambert-Eaton myasthenic syndrome) and the other that is a pure autoimmune form (NP-Lambert-Eaton myasthenic syndrome)", "LEMS weakness typically involves lower and upper limbs and the proximal muscles are predominantly affected. A significant proportion of patients also have dysfunction of the autonomic nervous system that may include dry mouth, constipation, blurred vision, impaired sweating, and orthostatic hypotension. LEMS recognition is based on clinical, electrophysiological and immunological criteria. Nearly 50-60% of patients with LEMS have an underlying tumour that, in almost all cases, is a small-cell lung cancer;", "In Lambert-Eaton myasthenic syndrome (LEMS), antibodies against presynaptic voltage-gated calcium channels reduce the quantal release of acetylcholine, causing muscle weakness and autonomic dysfunction. More than half of the affected patients have associated small cell lung cancer", "The Lambert-Eaton myasthenic syndrome (LEMS) is a disease of neuromuscular transmission in which autoantibodies against the P/Q-type voltage-gated calcium channel (VGCC) at the presynaptic nerve terminal play a major role in decreasing quantal release of acetylcholine (ACh), resulting in skeletal muscle weakness and autonomic symptoms.", "Primary respiratory failure as the presenting symptom in Lambert-Eaton myasthenic syndrome.", "Lambert-Eaton myasthenic syndrome is a neuromuscular junction disorder characterized by proximal limb muscle weakness, fatigability, decreased deep-tendon reflexes, and autonomic symptoms.", " Lambert-Eaton myasthenic syndrome is a neuromuscular junction disorder characterized by proximal limb muscle weakness, fatigability, decreased deep-tendon reflexes, and autonomic symptoms. There are 2 forms of Lambert-Eaton myasthenic syndrome: one most frequently associated with small-cell lung cancer (P-Lambert-Eaton myasthenic syndrome) and the other that is a pure autoimmune form (NP-Lambert-Eaton myasthenic syndrome).", "The Lambert-Eaton myasthenic syndrome (LEMS) is a neuromuscular disorder, often associated with small cell lung carcinoma (SCLC), which is characterized by reduced quantal release of acetylcholine from the motor nerve terminals. LAMBERT-EATON MYASTHENIC SYNDROME: The Lambert-Eaton Myasthenic Syndrome (LEMS) is characterized by proximal muscle weakness initially affecting gait, autonomic symptoms (dry mouth, constipation, erectile failure) and augmentation of strength during initial voluntary activation.", "LAMBERT-EATON MYASTHENIC SYNDROME: The Lambert-Eaton Myasthenic Syndrome (LEMS) is characterized by proximal muscle weakness initially affecting gait, autonomic symptoms (dry mouth, constipation, erectile failure) and augmentation of strength during initial voluntary activation.", "Primary respiratory failure as the presenting symptom in Lambert-Eaton myasthenic syndrome." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/8505927", "http://www.ncbi.nlm.nih.gov/pubmed/16526254", "http://www.ncbi.nlm.nih.gov/pubmed/24481713", "http://www.ncbi.nlm.nih.gov/pubmed/24114606", "http://www.ncbi.nlm.nih.gov/pubmed/21822385", "http://www.ncbi.nlm.nih.gov/pubmed/18653248" ]

[]

[]

[ "Pyroptosis is an inflammasome-mediated programmed cell death pathway." ]

[]

[ "pyroptotic cell death,", " pyroptotic cell death", "Pyroptosis is an inflammasome-mediated programmed cell death pathway triggered in macrophages by a variety of stimuli, including intracellular bacterial pathogens. ", "pyroptotic death ", "C. albicans triggers pyroptosis, a proinflammatory macrophage death", "Pyroptosis is a caspase-1-dependent pro-inflammatory form of programmed cell death", "associated with pyroptosis, the pro-inflammatory programmed cell death", "Our study here identified a novel cell death, pyroptosis in ox-LDL induced human macrophage, which may be implicated in lesion macrophages death and play an important role in lesion instability.", "pyroptotic cell death", " caspase-1-induced pyroptotic cell death ", "Caspase-1-induced pyroptosis is an innate immune effector mechanism against intracellular bacteria." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/26056317", "http://www.ncbi.nlm.nih.gov/pubmed/25043180", "http://www.ncbi.nlm.nih.gov/pubmed/21178113", "http://www.ncbi.nlm.nih.gov/pubmed/24667705", "http://www.ncbi.nlm.nih.gov/pubmed/25341033", "http://www.ncbi.nlm.nih.gov/pubmed/24376002", "http://www.ncbi.nlm.nih.gov/pubmed/23816851", "http://www.ncbi.nlm.nih.gov/pubmed/21057511", "http://www.ncbi.nlm.nih.gov/pubmed/25418070", "http://www.ncbi.nlm.nih.gov/pubmed/23637985" ]

[]

[ "http://www.disease-ontology.org/api/metadata/DOID:649", "http://www.disease-ontology.org/api/metadata/DOID:12858", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D000069292", "http://www.disease-ontology.org/api/metadata/DOID:1393", "http://www.disease-ontology.org/api/metadata/DOID:6576", "http://www.disease-ontology.org/api/metadata/DOID:6575" ]

[ "Bacteria such as A. actinomycetemcomitans, P. gingivalis, T. forsythensis, T. denticola, P. intermedia and F. nucleatum are associated with the progression of peri-implantitis." ]

[ "A. actinomycetemcomitans", "P. gingivalis", "T. denticola", "T. forsythia", "P. intermedia", "F. nucleatum" ]

[ " Later, the specific plaque hypothesis established the role of some microorganisms such as A. actinomycetemcomitans, P. gingivalis, T. forsythensis, T. denticola, P. intermedia and F. nucleatum in different forms of periodontal diseases", "The microbiological analysis revealed that the total bacterial load increased during the period following ligature removal and established an anaerobic Gram-negative microflora.", "Most periodontal pathogens are common saprophytes of the oral cavity, expressing their virulence only in a susceptible host or when some changes come about in the oral environment", "Overall, the types and relative proportions of putative periodontal pathogens in plaque associated with ligature-induced peri-implantitis and ligature-induced periodontitis were similar. Only levels of anaerobic Actinomyces and spirochetes were significantly different between both sites" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/20976394", "http://www.ncbi.nlm.nih.gov/pubmed/9526919", "http://www.ncbi.nlm.nih.gov/pubmed/14598129", "http://www.ncbi.nlm.nih.gov/pubmed/23937262" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D057873" ]

[ "All known deadenylases belong to either the DEDD or the exonuclease–endonuclease–phosphatase (EEP) superfamily. Members of DEDD include the POP2, CAF1Z, PARN and PAN2 families. Members of EEP include the CCR4, Nocturnin, ANGEL and 2'-PDE families." ]

[ "POP2", "CAF1Z", "PARN", "PAN2", "CCR4", "Nocturnin", "ANGEL", "2'-PDE" ]

[ "Among the deadenylase family, poly(A)-specific ribonuclease (PARN) is unique in its domain composition, which contains three potential RNA-binding domains: the catalytic nuclease domain, the R3H domain and the RRM domain", "On the other hand, the interaction between CNOT7 and BTG2, a member of the antiproliferative BTG/Tob family involved in transcription and mRNA decay appears less important for proliferation of MCF7 cells, suggesting that CNOT7 does not function solely in conjunction with BTG2.", "The Tob/BTG family is a group of antiproliferative proteins containing two highly homologous regions, Box A and Box B. These proteins all associate with CCR4-associated factor 1 (Caf1), which belongs to the ribonuclease D (RNase D) family of deadenylases and is a component of the CCR4-Not deadenylase complex.", "The CCR4 family proteins are 3'-5'-deadenylases that function in the first step of the degradation of poly(A) mRNA.", "CCR4, an evolutionarily conserved member of the CCR4-NOT complex, is the main cytoplasmic deadenylase. It contains a C-terminal nuclease domain with homology to the endonuclease-exonuclease-phosphatase (EEP) family of enzymes.", "The yeast Pop2 protein, belonging to the eukaryotic Caf1 family, is required for mRNA deadenylation in vivo.", "Although CAF1 protein belongs to the DEDDh family of RNases, CCR4 appears to be the principle deadenylase of the CCR4-NOT complex.", "Like CCR4, increased length of RNA substrates converted mCAF1 into a processive enzyme. In contrast to two other DEDD family members, PAN2 and PARN, mCAF1 was not activated either by PAB1 or capped RNA substrates.", "The domain has the fold of the DnaQ family and represents the first structure of an RNase from the DEDD superfamily.", "The evolutionarily conserved CCR4 protein, which is part of the cytoplasmic deadenylase, contains a C-terminal domain that displays homology to an Mg2+-dependent DNase/phosphatase family of proteins.", "These results establish that CCR4 and most probably other members of a widely distributed CCR4-like family of proteins constitute a novel class of RNA-DNA exonucleases.", "Deadenylases specifically catalyze the degradation of eukaryotic mRNA poly(A) tail in the 3'- to 5'-end direction with the release of 5'-AMP as the product.", "Shortening and removal of the 3' poly(A) tail of mature mRNA by poly(A)-specific 3' exonucleases (deadenylases) is the initial and often rate-limiting step in mRNA degradation.", "PARN, Nocturnin and Angel are three of the multiple deadenylases that have been described in eukaryotic cells." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/19605561", "http://www.ncbi.nlm.nih.gov/pubmed/11239395", "http://www.ncbi.nlm.nih.gov/pubmed/22442711", "http://www.ncbi.nlm.nih.gov/pubmed/12590136", "http://www.ncbi.nlm.nih.gov/pubmed/22817748", "http://www.ncbi.nlm.nih.gov/pubmed/23337855", "http://www.ncbi.nlm.nih.gov/pubmed/15769875", "http://www.ncbi.nlm.nih.gov/pubmed/21743004", "http://www.ncbi.nlm.nih.gov/pubmed/20628353", "http://www.ncbi.nlm.nih.gov/pubmed/12844354", "http://www.ncbi.nlm.nih.gov/pubmed/11747467", "http://www.ncbi.nlm.nih.gov/pubmed/21245038", "http://www.ncbi.nlm.nih.gov/pubmed/23388391", "http://www.ncbi.nlm.nih.gov/pubmed/19955262", "http://www.ncbi.nlm.nih.gov/pubmed/17766253", "http://www.ncbi.nlm.nih.gov/pubmed/11889047", "http://www.ncbi.nlm.nih.gov/pubmed/14618157", "http://www.ncbi.nlm.nih.gov/pubmed/23274303", "http://www.ncbi.nlm.nih.gov/pubmed/15044470", "http://www.ncbi.nlm.nih.gov/pubmed/19276069", "http://www.ncbi.nlm.nih.gov/pubmed/22073225", "http://www.ncbi.nlm.nih.gov/pubmed/21965533" ]

[ { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_51354137363100D", "o": "Cytoplasmic deadenylase" }, { "p": "http://purl.uniprot.org/core/fullName", "s": "http://linkedlifedata.com/resource/#_443256444B36007", "o": "mRNA deadenylase" } ]

[]

[ "The Askin tumor is a primitive malignant small-cell tumor of the chest wall mostly seen among children and adolescents. It is closely related to Ewing's sarcoma of the same location, with both tumors harboring reciprocal translocation t(11;22) (q24;q12)." ]

[ "reciprocal translocation t(11;22) (q24;q12)" ]

[ "The Ewing sarcoma family of tumors includes osseous Ewing sarcoma, extraskeletal Ewing sarcoma, primitive neuroectodermal tumor, and Askin tumor. They share a karyotype abnormality with translocation involving chromosomes 11 and 22", "Ewing tumor family consists of Ewing tumor of bone, extraosseous Ewing tumor, primitive neurectodermal tumor and Askin tumor. All of them share genetic abnormality, reciprocal translocation (11; 22) (q24; q12), and originate from the same primordial stem cell", "Chromosomal analysis of the neoplastic cells revealed translocation (11;22)(q24;q12), which is often found in Ewing's sarcoma and Askin tumor", "Malignant small cell tumor of the thoracopulmonary region (MSCT) was first described in 1979 and has been referred to as the Askin tumor", "MSCT and PPNET have a common reciprocal cytogenetic translocation [t(11;22)q(24;q12)], which is shared with Ewing's sarcoma", "The Askin tumor, a primitive malignant small-cell tumor of the chest wall, is mostly seen among children and adolescents. It is closely related to Ewing's sarcoma of the same location, both tumors showing a chromosomal translocation t(11;22)", "Chromosomal analysis of the neoplastic cells revealed translocation (11;22)(q24;q12), which is often found in Ewing's sarcoma and Askin tumor.", "Chromosomal analysis of the neoplastic cells revealed translocation (11;22)(q24;q12), which is often found in Ewing's sarcoma and Askin tumor.", "In Ewing's sarcoma (a tumor of unknown histogenesis), and in peripheral neuroepithelioma and Askin's tumor (tumors with evidence of neural origin), we have observed an indistinguishable t(11;22) translocation.", "Reciprocal translocations of chromosomes 11 and 22 are the most common cytogenetic abnormalities in Ewing's sarcoma and the related Askin's tumor", "The t(11;22)(q24;q12) and t(21;22)(q22;q12) are specific chromosomal translocations found in the Ewing family of tumors including ES, PNET and Askin tumors" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/7591257", "http://www.ncbi.nlm.nih.gov/pubmed/17009618", "http://www.ncbi.nlm.nih.gov/pubmed/2162733", "http://www.ncbi.nlm.nih.gov/pubmed/1333942", "http://www.ncbi.nlm.nih.gov/pubmed/7571088", "http://www.ncbi.nlm.nih.gov/pubmed/9213191", "http://www.ncbi.nlm.nih.gov/pubmed/23674776" ]

[]

[ "http://www.disease-ontology.org/api/metadata/DOID:0050608" ]

[ "AtxA is the gene encoding the trans-activator of anthrax toxin synthesis and is essential for virulence of B. anthracis. It is located on the resident 185-kb plasmid pXO1 and its activation is stimulated by bicarbonate. AtxA controls the expression of more than a hundred genes belonging to all genetic elements, the chromosome and both virulence plasmids, including those encoding the major virulence factors. AtxA can activate or repress gene expression. In atxA+ strains, toxin gene expression is increased 5- to 20-fold in cells grown in 5% CO2 relative to cells grown in air. Dual promoters control expression of AtxA. Transcription of the atxA gene occurs from two independent promoters, P1 and P2, whose transcription start sites are separated by 650 bp.", "Comparison of the resulting protein patterns indicated that synthesis of non-toxin proteins is influenced by growth in elevated CO2 and the toxin gene regulator, atxA. The AtxA virulence regulator of Bacillus anthracis is required for toxin and capsule gene expression. DNA sequence analysis of transposon insertion sites in 17 mutants carrying CO2- and atxA-regulated fusions revealed 10 mutants carrying independent insertions on the 185-kb toxin plasmid pXO1 which did not map to the toxin genes. We purified histidine-tagged AtxA [AtxA(His)] from Escherichia coli and used anti-AtxA(His) serum to detect AtxA in protein preparations from B. anthracis cells.", "The atxA gene product activates transcription of the anthrax toxin genes and is essential for virulence." ]

[]

[ "The atxA gene product activates transcription of the anthrax toxin genes and is essential for virulence.", "The atxA-null mutant is avirulent in mice", "These data suggest that the atxA gene product also regulates toxin gene expression during infection.", "Thus, we conclude that the pX01 influence on capsule synthesis is mediated by AtxA, the pXO1-encoded trans-activator of the toxin gene expression.", "atxA, the gene encoding the trans-activator of anthrax toxin synthesis", "The genes atxA, located on pXO1, and acpA, located on pXO2, encode positive trans-acting proteins that are involved in bicarbonate-mediated regulation of toxin and capsule production, respectively", " Transcription initiated from P1 and P2 was activated by both atxA and acpA, and activation appeared to be stimulated by bicarbonate.", "In atxA+ strains, toxin gene expression is increased 5- to 20-fold in cells grown in 5% CO2 relative to cells grown in air.", "Our data indicate a clear association of atxA with CO2-enhanced gene expression in B. anthracis and provide evidence that atxA regulates genes other than the structural genes for the anthrax toxin proteins.", " Our data strongly suggest that an additional factor(s) is involved in regulation of pag and that the relative amounts of such a factor(s) and AtxA are important for optimal toxin gene expression.", "Two regulatory genes, acpA and atxA, have been reported to control expression of the Bacillus anthracis capsule biosynthesis operon capBCAD", "The atxA gene is located on the virulence plasmid pXO1, while pXO2 carries acpA and the cap genes", "Dual promoters control expression of the Bacillus anthracis virulence factor AtxA.", "Here we report that transcription of the atxA gene occurs from two independent promoters, P1 (previously described by Dai et al. [Z. Dai, J. C. Sirard, M. Mock, and T. M. Koehler, Mol. Microbiol. 16:1171-1181, 1995]) and P2, whose transcription start sites are separated by 650 bp.", "AtxA controls the expression of more than a hundred genes belonging to all genetic elements, the chromosome and both virulence plasmids, including those encoding the major virulence factors. AtxA can activate or repress gene expression. ", "Here we employ 5' and 3' deletion analysis and site-directed mutagenesis of the atxA control region to demonstrate that atxA transcription from the major start site P1 is dependent upon a consensus sequence for the housekeeping sigma factor SigA and an A+T-rich upstream element for RNA polymerase.", "We also show that an additional trans-acting protein(s) binds specifically to atxA promoter sequences located between -13 and +36 relative to P1 and negatively impacts transcription. Deletion of this region increases promoter activity up to 15-fold.", "A majority of genes on the virulence plasmid pXO1 that are regulated by the presence of either CO2 or AtxA separately are also regulated synergistically in the presence of both. These results also elucidate novel pXO1-encoded small RNAs that are associated with virulence conditions.", "This response requires the presence of the pXO1 virulence plasmid-encoded pleiotropic regulator AtxA.", "Transcriptome analysis identifies Bacillus anthracis genes that respond to CO2 through an AtxA-dependent mechanism", "The majority of the regulated genes responded to both AtxA and carbon dioxide rather than to just one of these factors. Interestingly, we identified two previously unrecognized small RNAs that are highly expressed under physiological carbon dioxide concentrations in an AtxA-dependent manner", "This response requires the presence of the pXO1 virulence plasmid-encoded pleiotropic regulator AtxA.", "As a similar organization is found in transcription regulators in many other pathogens, AtxA might become the paradigm of a new class of virulence regulators.", "AtxA, a Bacillus anthracis global virulence regulator.", "Bacillus anthracis virulence regulator AtxA: oligomeric state, function and CO(2) -signalling.", "The accumulation of the global virulence regulator AtxA protein was strongly reduced in the mutant strain.", "This response requires the presence of the pXO1 virulence plasmid-encoded pleiotropic regulator AtxA", "This response requires the presence of the pXO1 virulence plasmid-encoded pleiotropic regulator AtxA. ", "Opposing effects of histidine phosphorylation regulate the AtxA virulence transcription factor in Bacillus anthracis.", "The B. anthracis pleiotropic regulator CodY activates toxin gene expression by post-translationally regulating the accumulation of the global regulator AtxA. ", "Cross-talk to the genes for Bacillus anthracis capsule synthesis by atxA, the gene encoding the trans-activator of anthrax toxin synthesis.", "AtxA, a unique regulatory protein of unknown molecular function, positively controls expression of the major virulence genes of Bacillus anthracis. ", "Consistent with the role of atxA in virulence factor expression, a B. anthracis atxA-null mutant is avirulent in a murine model for anthrax. ", "This response requires the presence of the pXO1 virulence plasmid-encoded pleiotropic regulator AtxA.", "PlcR is the first example described of a pleiotropic regulator involved in the control of extracellular virulence factor expression in pathogenic Bacillus spp.", "Bacillus anthracis virulence regulator AtxA: oligomeric state, function and CO(2) -signalling.", "AtxA, a unique regulatory protein of unknown molecular function, positively controls expression of the major virulence genes of Bacillus anthracis." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/14702298", "http://www.ncbi.nlm.nih.gov/pubmed/21911592", "http://www.ncbi.nlm.nih.gov/pubmed/19651859", "http://www.ncbi.nlm.nih.gov/pubmed/9199422", "http://www.ncbi.nlm.nih.gov/pubmed/9106214", "http://www.ncbi.nlm.nih.gov/pubmed/18676674", "http://www.ncbi.nlm.nih.gov/pubmed/22636778", "http://www.ncbi.nlm.nih.gov/pubmed/9234759", "http://www.ncbi.nlm.nih.gov/pubmed/17302796", "http://www.ncbi.nlm.nih.gov/pubmed/20863885", "http://www.ncbi.nlm.nih.gov/pubmed/10361306", "http://www.ncbi.nlm.nih.gov/pubmed/9119194", "http://www.ncbi.nlm.nih.gov/pubmed/8577251", "http://www.ncbi.nlm.nih.gov/pubmed/21923765", "http://www.ncbi.nlm.nih.gov/pubmed/24661624", "http://www.ncbi.nlm.nih.gov/pubmed/17302798" ]

[]

[ "http://www.biosemantics.org/jochem#4244018", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001408" ]

[ "Yes, cystatin C (CysC) is a novel biomarker of renal function." ]

[ "yes" ]

[ "to explore the effect of ageing on renal function with cystatin C as the marker of glomerular filtration rate (GFR) in the general population without vascular disease or diabetes.", "Cystatin C, a more specific kidney function biomarker, was also elevated at 24 h after CLP.", "This study evaluated FGF-23 as well as traditional markers of kidney disease, namely urine albumin-to-creatinine ratio (UACR) and creatinine-cystatin C estimated GFR (eGFRCrCyC), as risk factors for AKI in elderly individuals. ", "he primary predictor was estimated GFR (eGFR) calculated using serum cystatin C (eGFR(cys)).", "A number of recent reports have suggested that the cystatin C/creatinine (CysC/Cr) ratio might be a useful biomarker of renal function in pediatric patients.", "The CKD-EPI equation using cystatin C was the most precise method of renal function evaluation in patients with neurogenic bladder.", "Serum cystatin C (CysC) is an endogenous marker of kidney function.", "The urinary content of CysC reflects tubular epithelial dysfunction whereas that of NGAL also characterizes tubular atrophy.", "Estimated kidney function based on serum cystatin C ", ": Several formulas for glomerular filtration rate (GFR) estimation, based on serum creatinine or cystatin C, have been proposed. ", "he highest and lowest eGFR levels corresponded to the cystatin C-based and MDRD-4 equations, respectively. ", "The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) recently proposed an equation to estimate GFR in subjects without cirrhosis using both serum creatinine and cystatin C levels.", "Emerging evidence has shown that cystatin C may improve classification of glomerular filtration rate for defining chronic kidney disease in certain clinical populations and assist in understanding the complications of chronic kidney disease", "Beta-trace protein (BTP) and cystatin C (CysC) are novel biomarkers of renal function. ", "Cystatin C could improve chronic kidney disease (CKD) classification in HIV-infected women relative to serum creatinine.", " Iohexol clearance and cystatin C formulae identify a greater proportion of patients with a GFR <60 mL/min/1.73 m(2), which also predicts the development of AKI.", " Cystatin C was recently reported to be an endogenous surrogate of kidney function, and a high level of cystatin C is reported to be a strong predictor of CVD;", "Studies that have simultaneously compared measured GFR and estimated GFR (using endogenous filtration markers such as creatinine, or newer ones such as cystatin C or β-trace protein)" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/23698027", "http://www.ncbi.nlm.nih.gov/pubmed/23910705", "http://www.ncbi.nlm.nih.gov/pubmed/24114579", "http://www.ncbi.nlm.nih.gov/pubmed/24001705", "http://www.ncbi.nlm.nih.gov/pubmed/23577724", "http://www.ncbi.nlm.nih.gov/pubmed/23813702", "http://www.ncbi.nlm.nih.gov/pubmed/23571811", "http://www.ncbi.nlm.nih.gov/pubmed/24178972", "http://www.ncbi.nlm.nih.gov/pubmed/24262510", "http://www.ncbi.nlm.nih.gov/pubmed/23797027", "http://www.ncbi.nlm.nih.gov/pubmed/23574755", "http://www.ncbi.nlm.nih.gov/pubmed/23701892", "http://www.ncbi.nlm.nih.gov/pubmed/24300829", "http://www.ncbi.nlm.nih.gov/pubmed/23669156", "http://www.ncbi.nlm.nih.gov/pubmed/24321840", "http://www.ncbi.nlm.nih.gov/pubmed/23866593", "http://www.ncbi.nlm.nih.gov/pubmed/23744636" ]

[]

[ "http://www.uniprot.org/uniprot/CYT_COTJA", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D055316", "http://www.uniprot.org/uniprot/CYTC_RAT", "http://www.biosemantics.org/jochem#4262069", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0065009", "http://www.uniprot.org/uniprot/CYTC_HUMAN", "http://www.uniprot.org/uniprot/CYT_CHICK", "http://www.uniprot.org/uniprot/CYTC_MOUSE", "http://www.uniprot.org/uniprot/CYTC_SAISC", "http://www.uniprot.org/uniprot/CYT_NAJAT", "http://www.uniprot.org/uniprot/CYT_SOYBN", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0003014", "http://www.uniprot.org/uniprot/CYT_ONCKE", "http://www.uniprot.org/uniprot/CYTC_MACMU", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D054316", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0003674", "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D015415", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0090183", "http://www.uniprot.org/uniprot/CYTC_RABIT" ]

[ "The so-called Hilbert curve visualization can complement genome browsers and help to get further insights into the structure of one's data. An open-source application, called HilbertVis, has been developed for R/bioconductor that allows the user to produce and interactively explore such plots." ]

[ "HilbertVis" ]

[ "In many genomic studies, one works with genome-position-dependent data, e.g. ChIP-chip or ChIP-Seq scores. Using conventional tools, it can be difficult to get a good feel for the data, especially the distribution of features. This article argues that the so-called Hilbert curve visualization can complement genome browsers and help to get further insights into the structure of one's data. This is demonstrated with examples from different use cases. An open-source application, called HilbertVis, is presented that allows the user to produce and interactively explore such plots.AVAILABILITY: http://www.ebi.ac.uk/huber-srv/hilbert/." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/19297348" ]

[]

[ "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" ]

[ "Yes, the non-invasive preanatal test of cell-free fetal DNA is being used for fetal aneuploidy screening." ]

[ "yes" ]

[ "Non-invasive prenatal testing with cell-free DNA: US physician attitudes toward implementation in clinical practice.", "The aim of this study was to assess awareness, potential adoption, and current utilization of non-invasive prenatal testing (NIPT) analysis for common fetal aneuploidies among obstetricians", "Cell-free DNA has been used for fetal rhesus factor and sex determination, fetal aneuploidy screening, cancer diagnostics and monitoring, and other applications.", "The recent release of new, non-invasive prenatal tests for fetal aneuploidy using cell-free fetal DNA (cffDNA) has been hailed as a revolution in prenatal testing and has triggered significant commercial interest in the field.", "Non-invasive prenatal testing (NIPT) for aneuploidy using cell-free DNA in maternal plasma is revolutionizing prenatal screening and diagnosis.", "SNP-based non-invasive prenatal testing detects sex chromosome aneuploidies with high accuracy.", "Non-invasive prenatal testing (NIPT) of cell-free fetal DNA in maternal plasma is a novel approach, designed for detecting common aneuploidies in the fetus.", "This study aimed to develop a single-nucleotide polymorphism-based and informatics-based non-invasive prenatal test that detects sex chromosome aneuploidies early in pregnancy.", "RAPIDR: an analysis package for non-invasive prenatal testing of aneuploidy.", "Non-invasive prenatal testing for aneuploidy: current status and future prospects.", "Non-invasive prenatal testing of fetal whole chromosome aneuploidy by massively parallel sequencing.", "Attitudes towards non-invasive prenatal testing for aneuploidy among US adults of reproductive age.", "[Non-invasive prenatal test in the diagnosis of aneuploidy 13, 18 and 21--theoretical and practical aspects].", "To track and analyze two false positive cases from non-invasive prenatal testing for potential fetal aneuploidy.", "Non-invasive prenatal testing (NIPT) of fetal aneuploidy using cell-free fetal DNA is becoming part of routine clinical practice.", "To report secondary or additional findings arising from introduction of non-invasive prenatal testing (NIPT) for aneuploidy by whole genome sequencing as a clinical service.", "Israeli Society of Medical Genetics NIPT Committee Opinion 072013: Non-invasive prenatal testing of cell-free DNA in maternal plasma for detection of fetal aneuploidy.", "In recent years, technical advances in the molecular analysis of fetal DNA (e.g., digital PCR and massively parallel sequencing (MPS)) has enabled the successful implementation of noninvasive testing into clinical practice, such as fetal sex assessment, RhD genotyping, and fetal chromosomal aneuploidy detection.With the ability to decipher the entire fetal genome from maternal plasma DNA, we foresee that an increased number of non-invasive prenatal tests will be available for detecting many single-gene disorders in the near future", "First identified in 1997, cell-free fetal DNA (cffDNA) has just recently been used to detect fetal aneuploidy of chromosomes 13, 18, and 21, showing its potential to revolutionize prenatal genetic testing as a non-invasive screening tool", "Non-invasive prenatal testing (NIPT) using cell-free fetal DNA in maternal plasma has been developed for the detection of fetal aneuploidy", "Israeli Society of Medical Genetics NIPT Committee Opinion 072013: Non-invasive prenatal testing of cell-free DNA in maternal plasma for detection of fetal aneuploidy", "Non-invasive prenatal testing for fetal aneuploidies in the first trimester of pregnancy", "To explore the value of next-generation sequencing for the non-invasive prenatal testing of fetal chromosomal aneuploidies", "Secondary findings from non-invasive prenatal testing for common fetal aneuploidies by whole genome sequencing as a clinical service", "To report secondary or additional findings arising from introduction of non-invasive prenatal testing (NIPT) for aneuploidy by whole genome sequencing as a clinical service", "Secondary findings from non-invasive prenatal testing for common fetal aneuploidies by whole genome sequencing as a clinical service.", "Motivations for undertaking DNA sequencing-based non-invasive prenatal testing for fetal aneuploidy: a qualitative study with early adopter patients in Hong Kong.", "OBJECTIVE: To determine whether non-invasive prenatal testing by maternal plasma DNA sequencing can uncover all fetal chromosome aneuploidies in one simple sequencing event. ", "Non-invasive prenatal diagnosis of fetal aneuploidies using massively parallel sequencing-by-ligation and evidence that cell-free fetal DNA in the maternal plasma originates from cytotrophoblastic cells.", "Non-invasive prenatal testing (NIPT) using cell-free fetal DNA in maternal plasma has been developed for the detection of fetal aneuploidy.", "Non-invasive prenatal testing (NIPT) of cell-free fetal DNA in maternal plasma is a novel approach, designed for detecting common aneuploidies in the fetus.", "non-invasive prenatal tests for fetal aneuploidy using cell-free fetal DNA (cffDNA) has been hailed as a revolution in prenatal testing and has triggered significant commercial interest in the field.", " Non-invasive prenatal testing (NIPT) of fetal aneuploidy using cell-free fetal DNA is becoming part of routine clinical practice. RAPIDR (Reliable Accurate Prenatal non-Invasive Diagnosis R package) is an easy-to-use open-source R package that implements several published NIPT analysis methods.", "The clinical data collected thus far indicate that NIPT is highly sensitive in detecting trisomies 21 and 18, and fairly sensitive in detecting trisomy 13 and sex chromosome aneuploidies. Because false-positive results may occur, an abnormal result must be validated by invasive prenatal testing.", "When non-invasive prenatal screening for aneuploidy is available, maternal age alone should not be an indication for invasive prenatal diagnosis in a twin pregnancy. (II-2A) If non-invasive prenatal screening is not available, invasive prenatal diagnosis in twins should be offered to women aged 35 and over.", "Therefore, methods with high sensitivity and precision are required to detect and differentiate fetal DNA from the large background of maternal DNA. In recent years, technical advances in the molecular analysis of fetal DNA (e.g., digital PCR and massively parallel sequencing (MPS)) has enabled the successful implementation of noninvasive testing into clinical practice, such as fetal sex assessment, RhD genotyping, and fetal chromosomal aneuploidy detection.With the ability to decipher the entire fetal genome from maternal plasma DNA, we foresee that an increased number of non-invasive prenatal tests will be available for detecting many single-gene disorders in the near future.", "Non-invasive prenatal testing for fetal aneuploidies in the first trimester of pregnancy.", "Secondary findings from non-invasive prenatal testing for common fetal aneuploidies by whole genome sequencing as a clinical service.", "To explore the value of next-generation sequencing for the non-invasive prenatal testing of fetal chromosomal aneuploidies.", "[Cell-free nucleic acid-based non-invasive prenatal diagnosis of fetal aneuploidies].", "Maternal age alone is a poor minimum standard for prenatal screening for aneuploidy, and it should not be used a basis for recommending invasive testing when non-invasive prenatal screening for aneuploidy is available.", "Israeli Society of Medical Genetics NIPT Committee Opinion 072013: Non-invasive prenatal testing of cell-free DNA in maternal plasma for detection of fetal aneuploidy.", "Attitudes towards non-invasive prenatal testing for aneuploidy among US adults of reproductive age.", "The recent release of new, non-invasive prenatal tests for fetal aneuploidy using cell-free fetal DNA (cffDNA) has been hailed as a revolution in prenatal testing and has triggered significant commercial interest in the field.", "Non-invasive prenatal testing (NIPT) of fetal aneuploidy using cell-free fetal DNA is becoming part of routine clinical practice.", "Non-invasive prenatal testing (NIPT) by massively parallel sequencing is a useful clinical test for the detection of common fetal aneuploidies.", "The clinical data collected thus far indicate that NIPT is highly sensitive in detecting trisomies 21 and 18, and fairly sensitive in detecting trisomy 13 and sex chromosome aneuploidies." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/22500971", "http://www.ncbi.nlm.nih.gov/pubmed/23765643", "http://www.ncbi.nlm.nih.gov/pubmed/25478006", "http://www.ncbi.nlm.nih.gov/pubmed/25044397", "http://www.ncbi.nlm.nih.gov/pubmed/23712453", "http://www.ncbi.nlm.nih.gov/pubmed/24603453", "http://www.ncbi.nlm.nih.gov/pubmed/25543032", "http://www.ncbi.nlm.nih.gov/pubmed/23553438", "http://www.ncbi.nlm.nih.gov/pubmed/25138112", "http://www.ncbi.nlm.nih.gov/pubmed/24312358", "http://www.ncbi.nlm.nih.gov/pubmed/23299662", "http://www.ncbi.nlm.nih.gov/pubmed/22863603", "http://www.ncbi.nlm.nih.gov/pubmed/24783433", "http://www.ncbi.nlm.nih.gov/pubmed/26252102", "http://www.ncbi.nlm.nih.gov/pubmed/17186566", "http://www.ncbi.nlm.nih.gov/pubmed/10655451", "http://www.ncbi.nlm.nih.gov/pubmed/26080919", "http://www.ncbi.nlm.nih.gov/pubmed/24482806", "http://www.ncbi.nlm.nih.gov/pubmed/25449088", "http://www.ncbi.nlm.nih.gov/pubmed/21574485", "http://www.ncbi.nlm.nih.gov/pubmed/24990604", "http://www.ncbi.nlm.nih.gov/pubmed/23526649", "http://www.ncbi.nlm.nih.gov/pubmed/24352524", "http://www.ncbi.nlm.nih.gov/pubmed/21076134", "http://www.ncbi.nlm.nih.gov/pubmed/24667696", "http://www.ncbi.nlm.nih.gov/pubmed/23089167", "http://www.ncbi.nlm.nih.gov/pubmed/21749752", "http://www.ncbi.nlm.nih.gov/pubmed/21749753", "http://www.ncbi.nlm.nih.gov/pubmed/26237478", "http://www.ncbi.nlm.nih.gov/pubmed/23470070", "http://www.ncbi.nlm.nih.gov/pubmed/25238658" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004247", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011296" ]

[ "IRanges, GenomicRanges, and GenomicFeatures provide scalable data structures for representing annotated ranges on the genome, with special support for transcript structures, read alignments and coverage vectors. Computational facilities include efficient algorithms for overlap and nearest neighbor detection, coverage calculation and other range operations. This infrastructure directly supports more than 80 other Bioconductor packages, including those for sequence analysis, differential expression analysis and visualization.", "At the core of the infrastructure are three packages: IRanges, GenomicRanges, and GenomicFeatures. These packages provide scalable data structures for representing annotated ranges on the genome, with special support for transcript structures, read alignments and coverage vectors. Computational facilities include efficient algorithms for overlap and nearest neighbor detection, coverage calculation and other range operations. This infrastructure directly supports more than 80 other Bioconductor packages, including those for sequence analysis, differential expression analysis and visualization." ]

[ "IRanges", "GenomicRanges", "GenomicFeatures" ]

[ "At the core of the infrastructure are three packages: IRanges, GenomicRanges, and GenomicFeatures. These packages provide scalable data structures for representing annotated ranges on the genome, with special support for transcript structures, read alignments and coverage vectors. Computational facilities include efficient algorithms for overlap and nearest neighbor detection, coverage calculation and other range operations. This infrastructure directly supports more than 80 other Bioconductor packages, including those for sequence analysis, differential expression analysis and visualization." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/23950696" ]

[]

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

[ "Yes, dichlorphenamide is effective for periodic paralysis. Dichlorphenamide--a carbonic anhydrase inhibitor--has been shown in a controlled trial to prevent attacks for many patients with both hypokalemic and hypokalemic periodic paralysis." ]

[ "yes" ]

[ "BACKGROUND AND PURPOSE: Acetazolamide and dichlorphenamide are carbonic anhydrase (CA) inhibitors effective in the clinical condition of hypokalemic periodic paralysis (hypoPP).", "In one study dichlorphenamide (DCP) vs placebo was tested in two groups of participants: 42 with hypokalemic periodic paralysis (HypoPP) and 31 with hyperkalemic periodic paralysis (HyperPP), based on clinical criteria. Thirty-four of 42 participants with hypokalemic periodic paralysis completed both treatment phases. For the 34 participants having attack rate data for both treatment phases, the mean improvement in attack rate (P = 0.02) and severity-weighted attack rate (P = 0.01) on DCP relative to placebo were statistically significant. ", "AUTHORS' CONCLUSIONS: The largest included study that met our inclusion criteria suggested that DCP was effective in the prevention of episodic weakness in both hypokalemic and hyperkalemic periodic paralyses.", "For periodic paralysis, dichlorphenamide--a carbonic anhydrase inhibitor--has been shown in a controlled trial to prevent attacks for many patients with both hypokalemic and hypokalemic periodic paralysis. ", "Chronically, acetazolamide, dichlorphenamide, or potassium-sparing diuretics decrease attack frequency and severity but are of little value acutely. ", " In the HypoPP trial, there were 13 subjects who exhibited a preference (in terms of the end point) for either DCP or placebo, and 11 of these preferred DCP. In the PSPP trial, DCP significantly reduced attack rates relative to placebo. DCP also significantly reduced attack rates relative to placebo in the HypoPP subjects. We conclude that DCP is effective in the prevention of episodic weakness in both HypoPP and PSPP.", "Diclofenamid has now already been administered for 2 years. It is well tolerated and has suppressed further attacks.", "Three patients with Hypokalemic Periodic Paralysis (HOPP)-associated progressive interattack muscle weakness, who became unresponsive or worsened by acetazolamide, responded favorably to dichlorophenamide, a more potent carbonic anhydrase inhibitor. Dichlorophenamide in single-blind placebo-controlled trials, considerably improved functional strength in two of the patients and had a moderate but definite effect in the third.", "Dichlorophenamide should be considered as an alternate to acetazolamide in the treatment of patients with HOPP-associated interattack muscle weakness who have become unresponsive or worsened by acetazolamide.", "Acetazolamide and dichlorphenamide are carbonic anhydrase (CA) inhibitors effective in the clinical condition of hypokalemic periodic paralysis (hypoPP).", "For periodic paralysis, dichlorphenamide--a carbonic anhydrase inhibitor--has been shown in a controlled trial to prevent attacks for many patients with both hypokalemic and hypokalemic periodic paralysis.", "BACKGROUND AND PURPOSE: Acetazolamide and dichlorphenamide are carbonic anhydrase (CA) inhibitors effective in the clinical condition of hypokalemic periodic paralysis (hypoPP). Whether these drugs prevent vacuolar myopathy, which is a pathogenic factor in hypoPP, is unknown. ", "Acetazolamide and dichlorphenamide are carbonic anhydrase (CA) inhibitors effective in the clinical condition of hypokalemic periodic paralysis (hypoPP).", "For periodic paralysis, dichlorphenamide--a carbonic anhydrase inhibitor--has been shown in a controlled trial to prevent attacks for many patients with both hypokalemic and hypokalemic periodic paralysis. A second trial, comparing dichlorphenamide with acetazolamide versus placebo, is currently in progress.", "Despite our better understanding of the pathogenesis of these disorders, current treatments are largely empirical and the evidence in favor of specific therapy largely anecdotal. For periodic paralysis, dichlorphenamide--a carbonic anhydrase inhibitor--has been shown in a controlled trial to prevent attacks for many patients with both hypokalemic and hypokalemic periodic paralysis." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/3374500", "http://www.ncbi.nlm.nih.gov/pubmed/18345024", "http://www.ncbi.nlm.nih.gov/pubmed/6855804", "http://www.ncbi.nlm.nih.gov/pubmed/18426576", "http://www.ncbi.nlm.nih.gov/pubmed/10632100", "http://www.ncbi.nlm.nih.gov/pubmed/19019313", "http://www.ncbi.nlm.nih.gov/pubmed/18254068" ]

[]

[ "http://www.biosemantics.org/jochem#4249177", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004005" ]

[ "The Hydrocephalus Outcome Questionnaire (HOQ) is a simple, reliable, and valid measure of health status in children with hydrocephalus." ]

[]

[ "We sought to describe the natural history of this disorder, specifically its clinical presentation, disease course and long-term health status impact using the validated, disease-specific Hydrocephalus Outcome Questionnaire (HOQ)", "OBJECT: The Hydrocephalus Outcome Questionnaire (HOQ) is an established means of measuring quality of life, but the cognitive component of this questionnaire has never been formally compared with gold-standard neuropsychological test scores. ", "Patients completed lifestyle questionnaires, the hydrocephalus outcome questionnaire (HOQ) and underwent cognitive testing. ", "Measures of QOL were the Hydrocephalus Outcome Questionnaire and the Health Utilities Index Mark 3. ", "METHODS: The families of children between 5 and 18 years of age with previously treated hydrocephalus at 3 Canadian pediatric neurosurgery centers completed measures of QOL: the Hydrocephalus Outcome Questionnaire (HOQ) and the Health Utilities Index Mark 3 (HUI3).", "In older children with hydrocephalus, the cHOQ appears to be a scientifically reliable means of assessing long-term outcome. ", "The HOQ is a simple and very useful measurement for determining outcome in pediatric hydrocephalus.", "The authors' aim was to quantify the QOL for children with hydrocephalus and identify predictors of long-term outcome, using a reliable and validated outcome measure: the Hydrocephalus Outcome Questionnaire (HOQ).", "OBJECTIVE: To compare three separate methods for establishing interpretability for a health status measure, the Hydrocephalus Outcome Questionnaire (HOQ).", "These include general outcome measures such as the Pediatric Evaluation of Disability Inventory and the Functional Independence Measure for Children, which measure physical function and independence in chronically ill and disabled children as well as disease-specific measures for hydrocephalus (Hydrocephalus Outcome Questionnaire), cerebral palsy (gross motor function and performance measures), head injury (Pediatric Cerebral Performance Category and Children's Coma Scale), and oncology (Pediatric Cancer Quality-of-Life Inventory).", "An instrument to measure the health status in children with hydrocephalus: the Hydrocephalus Outcome Questionnaire.", " The authors developed a quantitative health status measure, the Hydrocephalus Outcome Questionnaire (HOQ), designed specifically for children with hydrocephalus, which can be completed by the children's parents.", "CONCLUSIONS: The HOQ for children with hydrocephalus demonstrated excellent reliability and validity properties. This tool will be valuable for a wide range of clinical research projects in pediatric hydrocephalus.", "OBJECT: In the preceding article, the authors described the Hydrocephalus Outcome Questionnaire (HOQ), a simple, reliable, and valid measure of health status in children with hydrocephalus.", "The authors' aim was to quantify the QOL for children with hydrocephalus and identify predictors of long-term outcome, using a reliable and validated outcome measure: the Hydrocephalus Outcome Questionnaire (HOQ).", "In the preceding article, the authors described the Hydrocephalus Outcome Questionnaire (HOQ), a simple, reliable, and valid measure of health status in children with hydrocephalus.", "The authors developed a quantitative health status measure, the Hydrocephalus Outcome Questionnaire (HOQ), designed specifically for children with hydrocephalus, which can be completed by the children's parents.", "The Hydrocephalus Outcome Questionnaire (HOQ) is an established means of measuring quality of life, but the cognitive component of this questionnaire has never been formally compared with gold-standard neuropsychological test scores.", "To compare three separate methods for establishing interpretability for a health status measure, the Hydrocephalus Outcome Questionnaire (HOQ).", "The authors developed a quantitative health status measure, the Hydrocephalus Outcome Questionnaire (HOQ), designed specifically for children with hydrocephalus, which can be completed by the children's parents. ", "OBJECTIVE: To compare three separate methods for establishing interpretability for a health status measure, the Hydrocephalus Outcome Questionnaire (HOQ). ", "The authors' aim was to quantify the QOL for children with hydrocephalus and identify predictors of long-term outcome, using a reliable and validated outcome measure: the Hydrocephalus Outcome Questionnaire (HOQ). ", "OBJECT: In the preceding article, the authors described the Hydrocephalus Outcome Questionnaire (HOQ), a simple, reliable, and valid measure of health status in children with hydrocephalus. ", "The authors developed a quantitative health status measure, the Hydrocephalus Outcome Questionnaire (HOQ), designed specifically for children with hydrocephalus, which can be completed by the children's parents.", "The HOQ is a simple and very useful measurement for determining outcome in pediatric hydrocephalus.", "These include general outcome measures such as the Pediatric Evaluation of Disability Inventory and the Functional Independence Measure for Children, which measure physical function and independence in chronically ill and disabled children as well as disease-specific measures for hydrocephalus (Hydrocephalus Outcome Questionnaire), cerebral palsy (gross motor function and performance measures), head injury (Pediatric Cerebral Performance Category and Children&apos;s Coma Scale), and oncology (Pediatric Cancer Quality-of-Life Inventory).", "Patients completed lifestyle questionnaires, the hydrocephalus outcome questionnaire (HOQ) and underwent cognitive testing. Clinical variables including number of shunt revisions, shunt infection and surgical decompression of foramen magnum, which may influence outcome, were investigated.", " Adult patients under routine follow-up were assessed in a joint neurosurgery/neuropsychology clinic. Patients completed lifestyle questionnaires, the hydrocephalus outcome questionnaire (HOQ) and underwent cognitive testing.", "The authors&apos; aim was to quantify the QOL for children with hydrocephalus and identify predictors of long-term outcome, using a reliable and validated outcome measure: the Hydrocephalus Outcome Questionnaire (HOQ).", "The Hydrocephalus Outcome Questionnaire (HOQ) is an established means of measuring quality of life, but the cognitive component of this questionnaire has never been formally compared with gold-standard neuropsychological test scores.", "Outcome in pediatric hydrocephalus: a comparison between previously used outcome measures and the hydrocephalus outcome questionnaire.", "Patients completed lifestyle questionnaires, the hydrocephalus outcome questionnaire (HOQ) and underwent cognitive testing.", "In the preceding article, the authors described the Hydrocephalus Outcome Questionnaire (HOQ), a simple, reliable, and valid measure of health status in children with hydrocephalus.", "Measures of QOL were the Hydrocephalus Outcome Questionnaire and the Health Utilities Index Mark 3." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/18754895", "http://www.ncbi.nlm.nih.gov/pubmed/17644917", "http://www.ncbi.nlm.nih.gov/pubmed/21778677", "http://www.ncbi.nlm.nih.gov/pubmed/19714338", "http://www.ncbi.nlm.nih.gov/pubmed/16238072", "http://www.ncbi.nlm.nih.gov/pubmed/21193992", "http://www.ncbi.nlm.nih.gov/pubmed/20593981", "http://www.ncbi.nlm.nih.gov/pubmed/21961548", "http://www.ncbi.nlm.nih.gov/pubmed/15835100", "http://www.ncbi.nlm.nih.gov/pubmed/18459898", "http://www.ncbi.nlm.nih.gov/pubmed/16426953", "http://www.ncbi.nlm.nih.gov/pubmed/15835099" ]

[]

[]

[ "Findings regarding association of maternal smoking and brain tumor risk are mixed. It was shown that children of women who smoked during pregnancy had an increased incidence of brain tumors (hazard ratio = 1.24; 95% confidence interval: 1.01-1.53). The increase in risk was similar for benign and malignant tumors, and was most apparent for astrocytoma. However, other authors did not find association between maternal smoking and brain tumor risk." ]

[]

[ "BACKGROUND: A recent meta-analysis suggested an association between exposure to paternal smoking during pregnancy and childhood brain tumor risk, but no studies have evaluated whether this association differs by polymorphisms in genes that metabolize tobacco-smoke chemicals.", "OBJECTIVE: Studies of the effect of maternal smoking during pregnancy on development of brain tumors in the offspring generally have found no increase in risk but most have mainly relied on retrospective exposure assessment. ", "Children of women who smoked during pregnancy had an increased incidence of brain tumors (hazard ratio = 1.24; 95% confidence interval: 1.01-1.53). The increase in risk was similar for benign and malignant tumors, and was most apparent for astrocytoma. ", "CONCLUSIONS: These results support a role for maternal smoking during pregnancy in the etiology of childhood brain tumors.", "Maternal occupational exposure to PAH before conception or during pregnancy was rare, and this exposure was not associated with any type of childhood brain tumor. ", "There was no association between the risk of brain tumors in the child and parental smoking prior to pregnancy, maternal smoking or regular exposure to others' cigarette smoke during pregnancy at home or at work, or passive smoking by the child during the first year of life.", "Maternal smoking during pregnancy and the risk of childhood brain tumors: a meta-analysis of 6566 subjects from twelve epidemiological studies.", "OBJECTIVE: Prior epidemiological studies suggest a possible association between maternal smoking during pregnancy and risk of childhood brain tumors.", "Pooling all twelve reports yielded an RRs of 1.05 (0.90-1.21), a non-statistically significant result suggesting no clear association between maternal smoking during pregnancy and risk of childhood brain tumor development.", ".CONCLUSION: The available epidemiological data do not support a clear association between maternal smoking during pregnancy and pediatric brain tumor development. ", "We observed only few positive associations, namely, between CNS tumors and low birth weight [<2,500 g; odds ratio (OR), 1.73; 95% confidence interval (CI), 1.06-2.84], between ependymoma and maternal smoking during pregnancy (>10 cigarettes per day: OR, 4.71; 95% CI, 1.69-13.1), and between astrocytoma and exposure to wood preservatives (OR, 1.91; 95% CI, 1.22-3.01). ", "The results on exposure to paternal tobacco smoke suggest an association with brain tumors (RR 1.22; CI, 1.05-1. 40; based on 10 studies) and lymphomas (RR 2.08; CI, 1.08-3.98; 4 studies). ", "No association was found between the risk of CBTs and maternal or paternal smoking before pregnancy and there was no association between CBTs and maternal smoking during pregnancy [odds ratio (OR) = 0.98; 95% confidence interval (CI) = 0.72-1.3]. A slightly increased OR for CBTs was found for paternal smoking during pregnancy in the absence of maternal smoking (OR = 1.2; 95% CI = 0.90-1.5) and for maternal exposure to passive smoke from any source (OR = 1.2; 95% CI = 0.95-1.6). The results of this analysis are consistent with results from several prior epidemiological studies that showed no significant association between CBTs and maternal smoking before or during pregnancy or maternal exposure to passive smoke during pregnancy.", "No significant differences in risks were found to be associated with maternal or paternal smoking at any time (odds ratio (OR) = 0.92 for mothers and 1.06 for fathers), during the year of birth of the child (which included both the prenatal and postnatal periods) (ORs = 0.84 for<1 pack/day and 1.0 for>or = 1 pack/day for mothers, and 0.68 for<1 pack/day and 1.07 for>or = 1 pack/day for fathers), or 2 years before the child was born, i.e., the pre-conception period (ORs = 0.75 for<1 pack/day and 1.01 for>or = 1 pack/day for mothers, and 0.90 for<1 pack/day and 1.15 for>or = 1 pack/day for fathers). Mothers were also specifically asked if they smoked during the pregnancy, and no association was found compared with never smokers (OR = 1.08, 95% confidence interval (CI) 0.80-1.45) or for ever-smokers who continued to smoke during pregnancy compared with those who stopped smoking during pregnancy (OR = 1.15, 95% CI 0.75-1.78). ", "The lack of an effect of parental smoking was observed for both the major histologic types and locations of brain tumors. These findings and those from earlier studies provide no support for the hypothesis that parental cigarette smoking influences the risk of brain tumors in children.", "Increased risk was associated with maternal contact with nitrosamine-containing substances such as burning incense (odds ratio, 3.3; p = 0.005), sidestream cigarette smoke (odds ratio, 1.5; p = 0.03), and face makeup (odds ratio, 1.6; p = 0.02); with maternal use of diuretics (odds ratio, 2.0; p = 0.03) and antihistamines (odds ratio, 3.4; p = 0.002); and with the level of maternal consumption of cured meats (p = 0.008).", "Prior epidemiological studies suggest a possible association between maternal smoking during pregnancy and risk of childhood brain tumors.", "Studies of the effect of maternal smoking during pregnancy on development of brain tumors in the offspring generally have found no increase in risk but most have mainly relied on retrospective exposure assessment.", "No association was found between the risk of CBTs and maternal or paternal smoking before pregnancy and there was no association between CBTs and maternal smoking during pregnancy [odds ratio (OR) = 0.98; 95% confidence interval (CI) = 0.72-1.3].", "There was no association between the risk of brain tumors in the child and parental smoking prior to pregnancy, maternal smoking or regular exposure to others' cigarette smoke during pregnancy at home or at work, or passive smoking by the child during the first year of life.", "RESULTS: We found positive interaction odds ratios (ORs) for both maternal and paternal smoking during pregnancy, EPHX1 H139R, and childhood brain tumors (P(interaction) = 0.02; 0.10), such that children with the high-risk (greater PAH activation) genotype were at a higher risk of brain tumors relative to children with the low-risk genotype when exposed to tobacco smoke during pregnancy. ", "Finally, no significant increase in risk of brain tumors was found for the child's passive exposure to parental smoking during the period from birth to diagnosis of the brain tumor in the case.", "Prior epidemiological studies suggest a possible association between maternal smoking during pregnancy and risk of childhood brain tumors.", "a non-statistically significant result suggesting no clear association between maternal smoking during pregnancy and risk of childhood brain tumor development.", "These results support a role for maternal smoking during pregnancy in the etiology of childhood brain tumors." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/7139628", "http://www.ncbi.nlm.nih.gov/pubmed/15191928", "http://www.ncbi.nlm.nih.gov/pubmed/24260161", "http://www.ncbi.nlm.nih.gov/pubmed/15801484", "http://www.ncbi.nlm.nih.gov/pubmed/12125967", "http://www.ncbi.nlm.nih.gov/pubmed/8470663", "http://www.ncbi.nlm.nih.gov/pubmed/12115571", "http://www.ncbi.nlm.nih.gov/pubmed/8850274", "http://www.ncbi.nlm.nih.gov/pubmed/11452935", "http://www.ncbi.nlm.nih.gov/pubmed/10620527" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D012907", "http://www.disease-ontology.org/api/metadata/DOID:368", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D001932", "http://www.disease-ontology.org/api/metadata/DOID:1319", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009035" ]

[ "Ficolin-3 activates lectin complement pathway." ]

[ "lectin complement pathway" ]

[ "This study aims to investigate whether an association exists between the ficolins that are part of the lectin complement pathway and SLE. ", "Ficolin-3 (also called H-ficolin or Hakata antigen) is a complement-activating pattern recognition molecule, possessing a fibrinogen-like domain involved in carbohydrate binding. ", "Lectin pathway activity via Ficolin-3 was measured in ELISA on acetylated bovine serum albumin (acBSA) and measured as Ficolin-3 binding and deposition of C4, C3 and the terminal complement complex (TCC).", "Furthermore, Ficolin-3 mediated complement activation may be valuable in monitoring disease activity in SLE patients due to the high sensitivity for complement consumption in the assay independent of the Ficolin-3 concentration.", "OBJECTIVES: To assess the involvement of ficolin-3, the main initiator of the lectin complement pathway (LCP), in subarachnoid hemorrhage (SAH) pathology and outcome.", "CONCLUSION: Our data provide evidence that LCP is activated after SAH and that the actual plasma concentrations of ficolin-3 reflect the severity of brain injury as evaluated by clinical and structural parameters. These results support the idea that ficolin-3-mediated functional LCP activity may be targeted to control injury progression in SAH.", "Ficolin-3-mediated lectin complement pathway activation in patients with subarachnoid hemorrhage.", "MBL-associated serine protease-3 circulates in high serum concentrations predominantly in complex with Ficolin-3 and regulates Ficolin-3 mediated complement activation.", "Moreover, Ficolin-3 has a high complement activating potential and is the only collagenase proteolytic resistant molecule among the lectin complement pathway initiators.", "Moreover, Ficolin-3 is the primary acceptor molecule of MASP-3 among the LCP activator molecules, but MASP-3 appears to down-regulate Ficolin-3 mediated complement activation through the lectin pathway.", "Ficolin-3 (Hakata antigen or H-ficolin) is a soluble pattern recognition molecule in the lectin complement pathway.", "Ficolin-3, encoded by the FCN3 gene and expressed in the lung and liver, is a recognition molecule in the lectin pathway of the complement system.", "Ficolin-1, -2 and -3 are recognition molecules in the lectin complement pathway and form complexes with serine proteases named MASP-1, -2 and -3 and two nonenzymatic proteins. MASP-2 is the main initiator of lectin pathway activation, while ficolin-3 is the most abundant ficolin molecule in the circulation.", "Ficolin-3 (also called H-ficolin or Hakata antigen) is a complement-activating pattern recognition molecule, possessing a fibrinogen-like domain involved in carbohydrate binding. Amongst human ficolins, Ficolin-3 has the highest concentration in serum and is the most potent lectin pathway activator in vitro.", "Moreover, Ficolin-3 is the primary acceptor molecule of MASP-3 among the LCP activator molecules, but MASP-3 appears to down-regulate Ficolin-3 mediated complement activation through the lectin pathway.", "Moreover, these LPS/ficolin-3 complexes activated the lectin pathway of complement in a C4b-deposition assay in a calcium- and magnesium-dependent way." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/18006063", "http://www.ncbi.nlm.nih.gov/pubmed/25069872", "http://www.ncbi.nlm.nih.gov/pubmed/19939495", "http://www.ncbi.nlm.nih.gov/pubmed/23142462", "http://www.ncbi.nlm.nih.gov/pubmed/24336142", "http://www.ncbi.nlm.nih.gov/pubmed/19535802", "http://www.ncbi.nlm.nih.gov/pubmed/25178935", "http://www.ncbi.nlm.nih.gov/pubmed/18261799", "http://www.ncbi.nlm.nih.gov/pubmed/21890891" ]

[]

[ "http://www.uniprot.org/uniprot/FCN3_HUMAN" ]

[ "Yes, nivolumab used for treatment of Non–Small-Cell Lung Cancer." ]

[ "yes" ]

[ "BACKGROUND: Patients with advanced squamous-cell non-small-cell lung cancer (NSCLC) who have disease progression during or after first-line chemotherapy have limited treatment options. This randomized, open-label, international, phase 3 study evaluated the efficacy and safety of nivolumab, a fully human IgG4 programmed death 1 (PD-1) immune-checkpoint-inhibitor antibody, as compared with docetaxel in this patient population.", "CONCLUSIONS: Among patients with advanced, previously treated squamous-cell NSCLC, overall survival, response rate, and progression-free survival were significantly better with nivolumab than with docetaxel, regardless of PD-L1 expression level.", "Agents currently in active clinical development for lung cancer include ipilimumab, which modulates the cytotoxic T-lymphocyte-associated antigen 4 pathway, and multiple agents targeting the programmed death protein 1 (PD-1) pathway, both anti-PD-1 compounds (nivolumab, pembrolizumab [MK-3475]) and those that target programmed death ligand 1 (PD-L1), a key ligand for PD-1 (BMS-936559, MPDL3280A).", "Overall Survival and Long-Term Safety of Nivolumab (Anti-Programmed Death 1 Antibody, BMS-936558, ONO-4538) in Patients With Previously Treated Advanced Non-Small-Cell Lung Cancer.", "We report overall survival (OS), response durability, and long-term safety in patients with non-small-cell lung cancer (NSCLC) receiving nivolumab in this trial.PATIENTS AND METHODS: Patients (N = 129) with heavily pretreated advanced NSCLC received nivolumab 1, 3, or 10 mg/kg intravenously once every 2 weeks in 8-week cycles for up to 96 weeks. ", "CONCLUSION: Nivolumab monotherapy produced durable responses and encouraging survival rates in patients with heavily pretreated NSCLC. Randomized clinical trials with nivolumab in advanced NSCLC are ongoing.", "Two PD-1 inhibitors, Bristol-Myers Squibb's nivolumab and Merck's MK-3475, both demonstrated positive results in phase I trials of previously treated patients with non-small cell lung cancer, reported at the World Conference on Lung Cancer in Sydney, Australia.", "Recently, many trials addressed the role of such therapies for metastatic NSCLC treatment: ipilimumab, tremelimumab, nivolumab and lambrolizumab are immunotherapeutic agents of main interest in this field.", "Two PD-1 inhibitors, Bristol-Myers Squibb&apos;s nivolumab and Merck&apos;s MK-3475, both demonstrated positive results in phase I trials of previously treated patients with non-small cell lung cancer, reported at the World Conference on Lung Cancer in Sydney, Australia", "Nivolumab, pembrolizumab (formerly known as MK-3475 and lambrolizumab), and pidilizumab are anti-PD-1 antibodies in clinical development for melanoma, non-small cell lung cancer, renal cell carcinoma, head and neck cancers, lymphoma, and several other cancers", "Nivolumab versus Docetaxel in Advanced Squamous-Cell Non-Small-Cell Lung Cancer.", "Activity and safety of nivolumab, an anti-PD-1 immune checkpoint inhibitor, for patients with advanced, refractory squamous non-small-cell lung cancer (CheckMate 063): a phase 2, single-arm trial.", " Patients with squamous non-small-cell lung cancer that is refractory to multiple treatments have poor outcomes. We assessed the activity of nivolumab, a fully human IgG4 PD-1 immune checkpoint inhibitor antibody, for patients with advanced, refractory, squamous non-small-cell lung cancer.", " Nivolumab has clinically meaningful activity and a manageable safety profile in previously treated patients with advanced, refractory, squamous non-small cell lung cancer. These data support the assessment of nivolumab in randomised, controlled, phase 3 studies of first-line and second-line treatment." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/26028407", "http://www.ncbi.nlm.nih.gov/pubmed/25897158", "http://www.ncbi.nlm.nih.gov/pubmed/24685885", "http://www.ncbi.nlm.nih.gov/pubmed/25704439", "http://www.ncbi.nlm.nih.gov/pubmed/25965365", "http://www.ncbi.nlm.nih.gov/pubmed/24402925", "http://www.ncbi.nlm.nih.gov/pubmed/25496336" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D002289", "http://www.disease-ontology.org/api/metadata/DOID:3908" ]

[ "There are many different approaches to enrich for phosphorylated peptides: titanium dioxide, IMAC, simple derivatization through phosphoramidate chemistry and antibodies." ]

[ "enriched for phosphorylated peptides using titanium dioxide", "sequential elution from IMAC", "simple derivatization procedure based on phosphoramidate chemistry", "antiphosphotyrosine antibodies" ]

[ "TiSH--a robust and sensitive global phosphoproteomics strategy employing a combination of TiO2, SIMAC, and HILIC.", "An initial TiO(2) phosphopeptide pre-enrichment step is followed by post-fractionation using sequential elution from IMAC (SIMAC) to separate multi- and mono-phosphorylated peptides, and hydrophilic interaction liquid chromatography (HILIC) of the mono-phosphorylated peptides (collectively abbreviated \"TiSH\").", "After enrichment by anti-phosphotyrosine antibodies, we identified 29 potential novel c-Src substrate proteins.", "Combining immunoprecipitation with an antiphosphotyrosine antibody, titanium dioxide phosphopeptide enrichment, isobaric tag for the relative and absolute quantitation methodology, and strong cation exchange separation, we were able to identify 2814 phosphopeptides.", "Phosphopeptide fractionation by strong cation exchange chromatography combined with immobilized metal affinity chromatography (IMAC) enrichment enabled quantification of more than 8000 distinct phosphorylation sites in Ppt1 wild-type versus Ppt1-deficient yeast cells", "By employing titanium dioxide in addition to antiphosphotyrosine antibodies as enrichment methods, we identified 4164 phosphopeptides on 1670 phosphoproteins.", "Our method combines the use of strong cation exchange (SCX) and titanium dioxide (TiO(2)) for phosphopeptide enrichment, high-resolution MS for peptide and protein identification, and stable isotope labeling by amino acids in cell culture (SILAC) for quantification.", "Phosphopeptides were isolated with high specificity through a simple derivatization procedure based on phosphoramidate chemistry." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/22345495", "http://www.ncbi.nlm.nih.gov/pubmed/20340162", "http://www.ncbi.nlm.nih.gov/pubmed/22369663", "http://www.ncbi.nlm.nih.gov/pubmed/20927383", "http://www.ncbi.nlm.nih.gov/pubmed/22499768", "http://www.ncbi.nlm.nih.gov/pubmed/21822884", "http://www.ncbi.nlm.nih.gov/pubmed/22499769", "http://www.ncbi.nlm.nih.gov/pubmed/23485197", "http://www.ncbi.nlm.nih.gov/pubmed/22906719", "http://www.ncbi.nlm.nih.gov/pubmed/17372656" ]

[ { "p": "http://linkedlifedata.com/resource/umls/altMetaMap", "s": "http://linkedlifedata.com/resource/umls/id/C0031684", "o": "http://linkedlifedata.com/resource/umls/label/A0319731" } ]

[ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D010748", "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=D045163", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D040901" ]

[ "This is accompanied by reductions in the level of H3K36 trimethylation, a posttranslational histone modification associated with efficient transcriptional elongation, and the number of full-length transcripts from these genes. The 3' ZNF exons contain H3K36me3, a mark of transcriptional elongation." ]

[ "H3K36me3" ]

[ " This is accompanied by reductions in the level of H3K36 trimethylation, a posttranslational histone modification associated with efficient transcriptional elongation, and the number of full-length transcripts from these genes.", "Also like BUR kinase and the PAF complex, the Spt5 CTR is important for histone H2B K123 monoubiquitination and histone H3 K4 and K36 trimethylation during transcription elongation.", "A positive feedback loop links opposing functions of P-TEFb/Cdk9 and histone H2B ubiquitylation to regulate transcript elongation in fission yeas", " Mono-ubiquitylation of histone H2B (H2Bub1) plays a key role in coordinating co-transcriptional histone modification by promoting site-specific methylation of histone H3", "We further characterized the histone modifications at the 3' ZNF exons and found that these regions also contain H3K36me3, a mark of transcriptional elongation.", "To test the hypothesis that the contradictory modifications are due to imprinting, we used a SNP analysis of RNA-seq data to demonstrate that both alleles of certain ZNF genes having H3K9me3 and H3K36me3 are transcribed. We next analyzed isolated ZNF 3' exons using stably integrated episomes.", "Set2-mediated H3 Lys(36) methylation is a histone modification that has been demonstrated to function in transcriptional elongation by recruiting the Rpd3S histone deacetylase complex to repress intragenic cryptic transcription.", "Overall, our results show and suggest that multiple H4, H2A, and H3 residues contribute to and form a Set2 docking/recognition site on the nucleosomal surface so that proper Set2-mediated H3 Lys(36) di- and trimethylation, histone acetylation, and transcriptional elongation can occur.", "Sp3 depletion correlated with increased H3K36me3 and H2Bub1, two histone modifications associated with transcription elongation", "Using a SIR-regulated heat shock-inducible transgene, hsp82-2001, and a natural drug-inducible subtelomeric gene, YFR057w, as models we demonstrate that substantial transcriptional induction (&gt;200-fold) can occur in the context of restricted histone loss and negligible levels of H3K4 trimethylation, H3K36 trimethylation and H3K79 dimethylation, modifications commonly linked to transcription initiation and elongation", "Sp3 depletion correlated with increased H3K36me3 and H2Bub1, two histone modifications associated with transcription elongation. ", "Sp3 depletion correlated with increased H3K36me3 and H2Bub1, two histone modifications associated with transcription elongation." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/21347206", "http://www.ncbi.nlm.nih.gov/pubmed/19365074", "http://www.ncbi.nlm.nih.gov/pubmed/20139424", "http://www.ncbi.nlm.nih.gov/pubmed/23401853", "http://www.ncbi.nlm.nih.gov/pubmed/22876190", "http://www.ncbi.nlm.nih.gov/pubmed/24722509", "http://www.ncbi.nlm.nih.gov/pubmed/24600005" ]

[]

[ "http://amigo.geneontology.org/amigo/term/GO:0016570", "http://www.biosemantics.org/jochem#4278518", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D042421" ]

[ "No" ]

[ "no" ]

[ "We demonstrated that thyroid hormone T3 rapidly induces Akt activation in pancreatic beta cells rRINm5F and hCM via thyroid hormone receptor (TR) beta1.", "The silencing of TRbeta1 expression through RNAi confirmed this receptor to be crucial for the T3-induced activation of Akt.", "T3 is able to specifically activate Akt in the islet beta cells rRINm5F and hCM through the interaction between TRbeta1 and PI3K p85alpha, demonstrating the involvement of TRbeta1 in this novel T3 non-genomic action in islet beta cells." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/17293442" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011988", "http://www.uniprot.org/uniprot/THBA_XENLA", "http://www.uniprot.org/uniprot/INS_APLCA", "http://www.uniprot.org/uniprot/THB_SHEEP", "http://www.uniprot.org/uniprot/THB_PAROL", "http://www.uniprot.org/uniprot/THB_CHICK", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=0004887", "http://www.uniprot.org/uniprot/THB_DANRE", "http://www.uniprot.org/uniprot/THB_RAT", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D013963", "http://www.uniprot.org/uniprot/THB_HUMAN", "http://www.uniprot.org/uniprot/THB_CAIMO", "http://www.uniprot.org/uniprot/THB_MOUSE", "http://www.uniprot.org/uniprot/THB_LITCT", "http://www.nlm.nih.gov/cgi/mesh/2012/MB_cgi?field=uid&exact=Find+Exact+Term&term=D037042" ]

[ "schizophrenia and major depressive disorder. " ]

[ "schizophrenia", "major depressive disorder" ]

[ "A recent genome-wide analysis indicated that a polymorphism (rs2535629) of ITIH3 showed the strongest association signal with susceptibility to psychiatric disorders in Caucasian populations. ", "he aim of the study was to replicate the association of rs2535629 with schizophrenia and major depressive disorder (MDD) in Japanese subjects. ", "In the MDD-bipolar cross-disorder analysis, 15 SNPs exceeded genome-wide significance (P<5 × 10(-8)), and all were in a 248 kb interval of high LD on 3p21.1 (chr3:52 425 083-53 822 102, minimum P=5.9 × 10(-9) at rs2535629).", "However, there was no preferential transmission at the ITIH3 rs52535629 polymorphism (χ²=0.14, P=0.707)." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/22472876", "http://www.ncbi.nlm.nih.gov/pubmed/25461954", "http://www.ncbi.nlm.nih.gov/pubmed/24373612" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2015/MB_cgi?field=uid&exact=Find+Exact+Term&term=D011110" ]

[ "Pembrolizumab inhibits the programmed cell death 1 (PD-1) immune checkpoint and has antitumor activity in patients with advanced melanoma. Pembrolizumab is approved by the US Food and Drug Administration for the treatment of advanced melanoma, and additional regulatory approvals are expected across the oncologic spectrum for a variety of other agents that target these pathways." ]

[ "programmed cell death 1" ]

[ "gents currently in active clinical development for lung cancer include ipilimumab, which modulates the cytotoxic T-lymphocyte-associated antigen 4 pathway, and multiple agents targeting the programmed death protein 1 (PD-1) pathway, both anti-PD-1 compounds (nivolumab, pembrolizumab [MK-3475]) and those that target programmed death ligand 1 (PD-L1), a key ligand for PD-1 (BMS-936559, MPDL3280A). ", "Ipilimumab (CTLA-4) and pembrolizumab (PD-1) are approved by the US Food and Drug Administration for the treatment of advanced melanoma, and additional regulatory approvals are expected across the oncologic spectrum for a variety of other agents that target these pathways.", "Pembrolizumab inhibits the programmed cell death 1 (PD-1) immune checkpoint and has antitumor activity in patients with advanced melanoma.", "CONCLUSIONS: The anti-PD-1 antibody pembrolizumab prolonged progression-free survival and overall survival and had less high-grade toxicity than did ipilimumab in patients with advanced melanoma. ", "METHODS: We conducted a phase 2 study to evaluate the clinical activity of pembrolizumab, an anti-programmed death 1 immune checkpoint inhibitor, in 41 patients with progressive metastatic carcinoma with or without mismatch-repair deficiency.", "CONCLUSIONS: This study showed that mismatch-repair status predicted clinical benefit of immune checkpoint blockade with pembrolizumab. ", "The anti programmed cell death-1 (PD-1) antibodies pembrolizumab and nivolumab have been recently licensed by the Food and Drug Administration for the treatment of advanced melanoma. ", "We describe for the first time the case of an adult patient who developed autoimmune diabetes likely as a consequence of PD-1 inhibition with pembrolizumab. ", "Ipilimumab, an anti-cytotoxic T-lymphocyte antigen 4 antibody and pembrolizumab, a monoclonal antibody targeting programmed death 1 receptor may be a feasible treatment option in patients with metastatic mucosal melanoma", "Pembrolizumab, a humanized highly selective IgG4 anti-PD-1 monoclonal antibody, was recently approved for the treatment of advanced melanoma based on promising early-phase clinical data", "Anti-programmed-death-receptor-1 treatment with pembrolizumab in ipilimumab-refractory advanced melanoma: a randomised dose-comparison cohort of a phase 1 trial.", "Efficacy was similar in the two pembrolizumab groups. Rates of treatment-related adverse events of grade 3 to 5 severity were lower in the pembrolizumab groups (13.3% and 10.1%) than in the ipilimumab group (19.9%).CONCLUSIONS: The anti-PD-1 antibody pembrolizumab prolonged progression-free survival and overall survival and had less high-grade toxicity than did ipilimumab in patients with advanced melanoma. ", "BACKGROUND: The anti-programmed-death-receptor-1 (PD-1) antibody pembrolizumab has shown potent antitumour activity at different doses and schedules in patients with melanoma. We compared the efficacy and safety of pembrolizumab at doses of 2 mg/kg and 10 mg/kg every 3 weeks in patients with ipilimumab-refractory advanced melanoma.METHODS: In an open-label, international, multicentre expansion cohort of a phase 1 trial, patients (aged ?18 years) with advanced melanoma whose disease had progressed after at least two ipilimumab doses were randomly assigned with a computer-generated allocation schedule (1:1 final ratio) to intravenous pembrolizumab at 2 mg/kg every 3 weeks or 10 mg/kg every 3 weeks until disease progression, intolerable toxicity, or consent withdrawal. ", "Vemurafenib and dabrafenib are targeted agents for patients with BRAF mutation-positive melanoma. Ipilimumab, an anti-cytotoxic T-lymphocyte antigen 4 antibody and pembrolizumab, a monoclonal antibody targeting programmed death 1 receptor may be a feasible treatment option in patients with metastatic mucosal melanoma.", "Pembrolizumab, a humanized highly selective IgG4 anti-PD-1 monoclonal antibody, was recently approved for the treatment of advanced melanoma based on promising early-phase clinical data. Encouraging results have also been seen in other malignancies, and PD-1-targeted therapies are likely to markedly change the treatment landscape." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/25891173", "http://www.ncbi.nlm.nih.gov/pubmed/25324906", "http://www.ncbi.nlm.nih.gov/pubmed/24685885", "http://www.ncbi.nlm.nih.gov/pubmed/25605845", "http://www.ncbi.nlm.nih.gov/pubmed/25034862", "http://www.ncbi.nlm.nih.gov/pubmed/25828465", "http://www.ncbi.nlm.nih.gov/pubmed/25960664", "http://www.ncbi.nlm.nih.gov/pubmed/26028255" ]

[]

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

[ "Mutation rate, as reflected in recent evolutionary divergence and human nucleotide diversity, is markedly increased in later-replicating regions of the human genome. All classes of substitutions are affected, suggesting a generalized mechanism involving replication time-dependent DNA damage. DNA repair systems, in general, are less efficient in late replicating heterochromatic regions compared to early replicating euchromatic regions of the genome. In yeast the mutation rate increases with the replication timing by more than 30% between the earliest and the latest replicating regions. Limited evidence from one chromosome arm in Drosophila melanogaster suggests the opposite pattern, with regions overlapping early-firing origins showing increased levels of diversity and divergence. In humans DNA replication patterns help shape the mutational landscapes of normal and cancer genomes.", "Recent studies revealed a long suspected replication-timing effect on mutation rate, but the mechanisms that regulate the increase in mutation rate as the genome is replicated remain unclear. The mutations were distributed randomly throughout the genome, independent of replication timing. Here, we show that the mutation rate increases with the replication timing by more than 30% between the earliest and the latest replicating regions. Interestingly, 5% of the single base pair substitutions might represent double-slippage events that occurred at the junction of immediately adjacent repeats, resulting in a shift in the repeat boundary.", "Here we observe that mutation rate, as reflected in recent evolutionary divergence and human nucleotide diversity, is markedly increased in later-replicating regions of the human genome" ]

[ "yes" ]

[ "Here we observe that mutation rate, as reflected in recent evolutionary divergence and human nucleotide diversity, is markedly increased in later-replicating regions of the human genome", "ll classes of substitutions are affected, suggesting a generalized mechanism involving replication time-dependent DNA damage", "We show that mutation rate varies 6-fold across a single chromosome, that this variation is correlated with replication timing, and we propose a model to explain this variation that relies on the temporal separation of two processes for replicating past damaged DNA: error-free DNA damage tolerance and translesion synthesis.", "Recent studies revealed a long suspected replication-timing effect on mutation rate, but the mechanisms that regulate the increase in mutation rate as the genome is replicated remain unclear. ", "DNA repair systems, in general, are less efficient in late replicating heterochromatic regions compared to early replicating euchromatic regions of the genome.", "The mutational profile of the yeast genome is shaped by replication", "the mutation rate increases with the replication timing by more than 30% between the earliest and the latest replicating regions.", "Thus, we show that the leading replicating strands present an excess of C over G and of A over T in the genome of S. cerevisiae (reciprocally an excess of G + T over C + A in lagging strands)", "Late-replicating domains have higher divergence and diversity in Drosophila melanogaster", "Recent evidence also suggests that late replication is associated with high mutability in yeast.", "Limited evidence from one chromosome arm in Drosophila melanogaster suggests the opposite pattern, with regions overlapping early-firing origins showing increased levels of diversity and divergence", "The mutation rate for DNA mismatch repair null strains was approximately 1 mutation per genome per generation, 225-fold greater than the wild-type rate. The mutations were distributed randomly throughout the genome, independent of replication timing.", "Many single-nucleotide substitutions in cancer genomes arise because of errors in DNA replication, which is spatio-temporally stratified.", "Here we propose that DNA replication patterns help shape the mutational landscapes of normal and cancer genomes", "Using data on five fully sequenced cancer types and two personal genomes, we determined that the frequency of intergenic single-nucleotide substitution is significantly higher in late DNA replication timing regions, even after controlling for a number of genomic features", "we found that genomic regions in close spatial proximity to late-replicating domains display similar mutation spectra as the late-replicating regions themselves", "In addition, certain chromosome rearrangements found in cancer cells and in cells exposed to ionizing radiation display a significant delay in replication timing of >3 hours that affects the entire chromosome(2,3). Recent work from our lab indicates that disruption of discrete cis-acting autosomal loci result in an extremely late replicating phenotype that affects the entire chromosome(4).", "A conservative estimate is that at least 1-2% of new deleterious mutations affect some aspect of DNA replication, repair, or chromosome segregation. Since deleterious mutations can have an effect even as heterozygotes, this mutation accumulation can create an inherited background of late-acting mutations that themselves enhance mutation rate.", "Drake calculates that lytic RNA viruses display spontaneous mutation rates of approximately one per genome while most have mutation rates that are approximately 0.1 per genome (Drake 1993). This constancy of germline mutation rates among microbial species need not necessarily mean constancy of the somatic mutation rates.", "A recent flurry of reports correlates replication timing (RT) with mutation rates during both evolution and cancer.", "DNA replication timing, genome stability and cancer: late and/or delayed DNA replication timing is associated with increased genomic instability.", "Since deleterious mutations can have an effect even as heterozygotes, this mutation accumulation can create an inherited background of late-acting mutations that themselves enhance mutation rate.", "In addition, this method allows for the unambiguous identification of chromosomal rearrangements that correlate with changes in replication timing that affect the entire chromosome." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/23422670", "http://www.ncbi.nlm.nih.gov/pubmed/22023572", "http://www.ncbi.nlm.nih.gov/pubmed/23271586", "http://www.ncbi.nlm.nih.gov/pubmed/12941181", "http://www.ncbi.nlm.nih.gov/pubmed/9560368", "http://www.ncbi.nlm.nih.gov/pubmed/21666225", "http://www.ncbi.nlm.nih.gov/pubmed/19287383", "http://www.ncbi.nlm.nih.gov/pubmed/23821616", "http://www.ncbi.nlm.nih.gov/pubmed/22114361", "http://www.ncbi.nlm.nih.gov/pubmed/23327985", "http://www.ncbi.nlm.nih.gov/pubmed/24598232", "http://www.ncbi.nlm.nih.gov/pubmed/22046001" ]

[]

[]

[ "Some insect genomes have lost the capacity of synthesizing selenoproteins. Species without selenoproteins have been identified within Diptera, Lepidoptera, Hymenoptera and Coleoptera." ]

[]

[]

[ "http://www.ncbi.nlm.nih.gov/pubmed/22479358", "http://www.ncbi.nlm.nih.gov/pubmed/19744324", "http://www.ncbi.nlm.nih.gov/pubmed/15843685", "http://www.ncbi.nlm.nih.gov/pubmed/18698431", "http://www.ncbi.nlm.nih.gov/pubmed/22943432", "http://www.ncbi.nlm.nih.gov/pubmed/16260744", "http://www.ncbi.nlm.nih.gov/pubmed/19487332", "http://www.ncbi.nlm.nih.gov/pubmed/14710190" ]

[]

[]

[ "The mode of inheritance of Facioscapulohumeral muscular dystrophy is autosomal dominant." ]

[ "autosomal dominant" ]

[ "autosomal dominant mode of inheritance" ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/22551571" ]

[]

[ "http://www.uniprot.org/uniprot/FRG2_HUMAN", "http://www.disease-ontology.org/api/metadata/DOID:11727", "http://www.uniprot.org/uniprot/FRG2C_HUMAN", "http://www.uniprot.org/uniprot/FRG2B_HUMAN", "http://www.uniprot.org/uniprot/FRG1_HUMAN", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D020391", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009136", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D009135", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D040582", "http://www.disease-ontology.org/api/metadata/DOID:9884", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D014918", "http://www.uniprot.org/uniprot/FRG1_MOUSE", "http://www.disease-ontology.org/api/metadata/DOID:0050557" ]

[ "Nod proteins fight off bacterial infections by stimulating proinflammatory signaling and cytokine networks and by inducing antimicrobial effectors, such as nitric oxide and antimicrobial peptides. NOD1 engagement generates an inflammatory response via activation of NFκB and MAPK pathways and several inflammatory disorders, such as Crohn's disease and asthma, are linked to genetic changes in either Nod1 or Nod2. Nod1 is also critically implicated in shaping adaptive immune responses towards bacterial-derived constituents. Together, Nod1 and Nod2 represent central players in the control of immune responses to bacterial infections and inflammation. Mice deficient for both Nod1 and Nod2 had attenuated inflammatory pathology, reduced levels of inflammatory cytokines, and increased colonization of the mucosal tissue", "Nod1/2 DKO mice show increased susceptibility for intestinal permeability while vascular permeability was not affected. The present study analyzed Nod1 and Nod2 double deficient (Nod1/2 DKO) mice under physiological and inflammatory conditions. The increased intestinal permeability is associated with enhanced inflammatory cytokine production and epithelial cell proliferation in Nod1-deficient mice as compared with wild-type mice. However, the influence of Rip2 was strictly dependent on infection conditions that favored expression of the Salmonella pathogenicity island 2 (SPI-2) type III secretion system (TTSS), as Rip2 was dispensable for inflammation when mice were infected with bacteria grown under conditions that promoted expression of the SPI-1 TTSS.", "Nod1 and Nod2 control bacterial infections and inflammation" ]

[ "yes" ]

[ "Nod1 and Nod2 control bacterial infections and inflammation", "The Nod proteins Nod1 and Nod2 are two NLR family members that trigger immune defense in response to bacterial peptidoglycan", "Nod proteins fight off bacterial infections by stimulating proinflammatory signaling and cytokine networks and by inducing antimicrobial effectors, such as nitric oxide and antimicrobial peptides.", "Nod1 is also critically implicated in shaping adaptive immune responses towards bacterial-derived constituents.", "Together, Nod1 and Nod2 represent central players in the control of immune responses to bacterial infections and inflammation.", "The innate immune receptor Nod1 protects the intestine from inflammation-induced tumorigenesis.", "we show that Nod1 deficiency results in the increased development of both colitis-associated and Apc tumor suppressor-related colon tumors. In the absence of Nod1 signaling, there is a greater disruption of the intestinal epithelial cell barrier due to chemically induced injury as manifested by increased surface epithelial apoptosis early on during chemically induced colitis and increased intestinal permeability.", "The increased intestinal permeability is associated with enhanced inflammatory cytokine production and epithelial cell proliferation in Nod1-deficient mice as compared with wild-type mice.", "Depletion of the gut microbiota suppressed tumor development in Nod1-deficient mice, thus highlighting a link between the commensal bacteria within the intestine and the host innate immune Nod1 signaling pathway in the regulation inflammation-mediated colon cancer development.", " NOD1 protein is expressed in the eye and promotes ocular inflammation in a dose- and time-dependent fashion. ", "NOD1 expression in the eye and functional contribution to IL-1beta-dependent ocular inflammation in mice", "Polymorphisms in NOD1 are associated with autoinflammatory diseases characterized by uveitis such as Crohn's disease and sarcoidosis", "NOD1 is homologous to NOD2, which is responsible for an autosomal dominant form of uveitis. Nonetheless, the role of NOD1 in intraocular inflammation has not been explored.", "Nod1 and Nod2 regulation of inflammation in the Salmonella colitis model", "mice deficient for both Nod1 and Nod2 had attenuated inflammatory pathology, reduced levels of inflammatory cytokines, and increased colonization of the mucosal tissue", "The present study has demonstrated an unexpected role of Nod1 in the development of site-specific vascular inflammation, especially coronary arteritis.", "Nod1 ligands induce site-specific vascular inflammation", "Phenotyping of Nod1/2 double deficient mice and characterization of Nod1/2 in systemic inflammation and associated renal disease", "The present study analyzed Nod1 and Nod2 double deficient (Nod1/2 DKO) mice under physiological and inflammatory conditions", "Several inflammatory disorders, such as Crohn's disease and asthma, are linked to genetic changes in either Nod1 or Nod2.", "Systematic analysis of Nod1/2 DKO mice revealed a possible role of Nod1/2 in the development of renal disease during systemic inflammation.", "NOD1 and NOD2 Signaling in Infection and Inflammation", "NOD1 engagement generates an inflammatory response via activation of NFκB and MAPK pathways. ", "In addition we profile novel inhibitors of RIP2 and NOD1 itself, which specifically inhibit NOD1 ligand induced inflammatory signalling in the vasculature. ", "This data supports the potential utility of NOD1 and RIP2 as therapeutic targets in human disease where vascular inflammation is a clinical feature, such as in sepsis and septic shock.", "NOD1 expression elicited by iE-DAP in first trimester human trophoblast cells and its potential role in infection-associated inflammation", "This study aimed to investigate the expression and function of NOD1 in first trimester trophoblast cells, and evaluate the potential role of trophoblast cells in infection-associated inflammation", "NOD1 may have a role in mediating infection-associated inflammation. Once iE-DAP is recognized by NOD1, the inflammatory response may be induced via NOD1-RICK-NF-κB-mediated pathways.", "NOD1/2(-/-) mice were protected from HFD-induced inflammation, lipid accumulation, and peripheral insulin intolerance.", "In contrast, Nod1 gene-deficient mice developed enhanced joint inflammation with concomitant elevated levels of proinflammatory cytokines and cartilage damage, consistent with a model in which Nod1 controls the inflammatory reaction.", "These data indicate that the NLR family members Nod1 and Nod2 have different functions in controlling inflammation, and that intracellular Nod1-Nod2 interactions may determine the severity of arthritis in this experimental model.", "Whereas the lymphotoxin pathway was critical for the induction of the B cell chemoattractant CXCL13 in response to Nod1 agonists, B cell accumulation within the spleen following Nod1-induced systemic inflammation was independent of the lymphotoxin pathway.", "The effect of NOD1 and NOD2 activation on inflammation and the insulin signalling pathway was also assessed.", "Nonetheless, the role of NOD1 in intraocular inflammation has not been explored.", "A key role for the endothelium in NOD1 mediated vascular inflammation: comparison to TLR4 responses.", "We previously demonstrated that human first-trimester trophoblasts express Nod1 and Nod2, which trigger inflammation upon stimulation.", "In addition, recent studies have revealed a role for intracellular NOD1 receptors in the regulation of vascular inflammation and metabolism.", "In conclusion, the present findings describe an important role for NOD1 in the development of insulin resistance and inflammation in pregnancies complicated by GDM.", "Phenotyping of Nod1/2 double deficient mice and characterization of Nod1/2 in systemic inflammation and associated renal disease.", "Nod1 activation by bacterial iE-DAP induces maternal-fetal inflammation and preterm labor.", "The nucleotide-binding oligomerisation domain (NOD) intracellular molecules recognise a wide range of microbial products, as well as other intracellular danger signals, thereby initiating inflammation through activation of nuclear factor κB (NFκB). ", "Nod1 ligands induce site-specific vascular inflammation.", "The nucleotide oligomerization domain (NOD) intracellular molecules recognize a wide range of microbial products as well as other intracellular danger signals, thereby initiating inflammation through activation of nuclear factor KB (NFKB), a central regulator of the terminal processes of human labor and delivery. ", "CONCLUSIONS: We identify NOD proteins as innate immune components that are involved in diet-induced inflammation and insulin intolerance. ", "Nod1 and Nod2 regulation of inflammation in the Salmonella colitis model.", "In particular, muramyl peptides trigger inflammation, contribute to host defense against microbial infections, and modulate the adaptive immune response to antigens. ", "Systemic and tissue-specific inflammation was assessed using enzyme-linked immunosorbent assays in NOD ligand-injected mice. ", "CONCLUSIONS: We identify NOD proteins as innate immune components that are involved in diet-induced inflammation and insulin intolerance. Acute activation of NOD proteins by mimetics of bacterial PGNs causes whole-body insulin resistance, bolstering the concept that innate immune responses to distinctive bacterial cues directly lead to insulin resistance. ", "Interferon-gamma (IFN gamma), which is a potent pro-inflammatory cytokine in intestinal mucosal inflammation, activates CARD4/NOD1 mRNA transcription in a time- and dose-dependent manner and results in augmentation of CARD4/NOD1 protein in SW480 cells.", "These studies suggest that the Th1 cytokine, IFN gamma, activates CARD4/NOD1 transcription and regulate innate immune mechanisms in the condition of intestinal mucosal inflammation.", "NOD1 activation triggers inflammation,", "In contrast to enhanced leptin mRNA by LPS and TNFα, NOD1 activation suppressed leptin mRNA in adipocytes, suggesting the differential effects of NOD1 activation in adipocytes. Overall, our results suggest that NOD1 represents a novel target for adipose inflammation in obesity.", "NOD1 activation triggers inflammation, antimicrobial mechanisms and autophagy in both epithelial cells and murine macrophages.", "NOD1 is an intracellular immune receptor that senses peptidoglycan from Gram-negative bacteria and responds by inducing autophagy and activating NF-κB, leading to inflammation-mediated bacterial clearance; however chronic pathogens can evade NOD1-mediated clearance by altering peptidoglycan structure.", "Bacterial NOD1 activation is positioned as a component of metabolic endotoxemia that can contribute to hyperlipidemia, systemic inflammation and insulin resistance by acting directly on adipocytes.", "NOD1 ligand also caused inflammation and insulin resistance directly in primary hepatocytes from WT, but not NOD1(-/-), mice.", "We conclude that NOD1 activation reduced AHR in allergen-induced lung inflammation, which was accompanied by a reduction of allergen-specific T-cell proliferation.", "The effect of NOD1 and NOD2 activation on inflammation and the insulin signalling pathway was also assessed.", "Interferon-gamma (IFN gamma), which is a potent pro-inflammatory cytokine in intestinal mucosal inflammation, activates CARD4/NOD1 mRNA transcription in a time- and dose-dependent manner and results in augmentation of CARD4/NOD1 protein in SW480 cells." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/23740944", "http://www.ncbi.nlm.nih.gov/pubmed/17690884", "http://www.ncbi.nlm.nih.gov/pubmed/24829218", "http://www.ncbi.nlm.nih.gov/pubmed/24828250", "http://www.ncbi.nlm.nih.gov/pubmed/12813035", "http://www.ncbi.nlm.nih.gov/pubmed/18574154", "http://www.ncbi.nlm.nih.gov/pubmed/24279792", "http://www.ncbi.nlm.nih.gov/pubmed/22870324", "http://www.ncbi.nlm.nih.gov/pubmed/23712977", "http://www.ncbi.nlm.nih.gov/pubmed/20921147", "http://www.ncbi.nlm.nih.gov/pubmed/19074813", "http://www.ncbi.nlm.nih.gov/pubmed/21715553", "http://www.ncbi.nlm.nih.gov/pubmed/19074871", "http://www.ncbi.nlm.nih.gov/pubmed/24534531", "http://www.ncbi.nlm.nih.gov/pubmed/21330608", "http://www.ncbi.nlm.nih.gov/pubmed/25253572", "http://www.ncbi.nlm.nih.gov/pubmed/25732381", "http://www.ncbi.nlm.nih.gov/pubmed/21677137", "http://www.ncbi.nlm.nih.gov/pubmed/21469090", "http://www.ncbi.nlm.nih.gov/pubmed/23162548", "http://www.ncbi.nlm.nih.gov/pubmed/24041848", "http://www.ncbi.nlm.nih.gov/pubmed/23848281", "http://www.ncbi.nlm.nih.gov/pubmed/23259058" ]

[]

[ "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D007249", "http://www.nlm.nih.gov/cgi/mesh/2016/MB_cgi?field=uid&exact=Find+Exact+Term&term=D053474" ]

[ "Rheumatoid arthritis, multiple sclerosis, prion diseases, cancer and Alzheimer's disease are examples of diseases where protein citrullination involvement has been demonstrated." ]

[ "Multiple Sclerosis", "Alzheimer disease", "Rheumatoid Arthritis", "RA", "Prion Diseases", "Cancer" ]

[ "his modification has been linked to the pathogenesis of autoimmune diseases including rheumatoid arthritis (RA). ", "Over the past decade, PADs and protein citrullination have been commonly implicated as abnormal pathological features in neurodegeneration and inflammatory responses associated with diseases such as multiple sclerosis, Alzheimer disease and rheumatoid arthritis. ", "These findings suggest that PAD2 and citrullinated proteins may play a key role in the brain pathology of prion diseases. ", "We first discovered that abnormal myelin hypercitrullination, even in normal-appearing white matter, by peptidylarginine deiminases (PADs) correlates strongly with disease severity and might have an important role in MS progression.", " recent advances have shown that the once obscure modification known as citrullination is involved in the onset and progression of inflammatory diseases and cancer.", "These observations may reflect a role of P. gingivalis in the protein citrullination, which is related to the pathogenesis of RA.", "Protein citrullination has been detected in the CNS and associated with a number of neurological diseases.", "Protein and peptide citrullination are important in the development of rheumatoid arthritis", "citrullination has been shown to be associated with several diseases, such as cancer, multiple sclerosis, rheumatoid arthritis, and Alzheimer's disease.", " Our data thus suggest that autoantibody formation in response to citrullinated vimentin directly induces bone loss, providing a link between the adaptive immune system and bone.", "citrullinated protein also has a negative side, because this protein's accumulation in the brain is a possible cause of Alzheimer's disease. ", "The aim of the present work was to study the effect of tobacco smoking on disease progression in rheumatoid arthritis patients and its relation to anti-cyclical citrullinated peptide (anti-CCP) antibodies.", "It appears from our results that, tobacco smoking mostly play a role in progression of rheumatoid arthritis through tissue protein citrullination", "we have reported pathological characterization of PAD2 and citrullinated proteins in scrapie-infected mice, ", "aberrant citrullinated proteins could play a role in pathogenesis and have value as a marker for the postmortem classification of neurodegenerative diseases.", "We previously reported that abnormal protein citrullination by PAD2 has been closely associated with the pathogenesis of neurodegenerative disorders such as Alzheimer's disease and prion disease", "This study suggests that accumulated citrullinated proteins and abnormal activation of PAD2 may function in the pathogenesis of prion diseases and serve as potential therapeutic targets.", "PTMs such as citrullination due to alterations of peptidylarginine deiminase activity or generation of RA-specific epitopes, should be considered as a trigger in tolerance break.", "Protein citrullination is an important posttranslational modification recognized by rheumatoid arthritis (RA)-specific autoantibodies. ", "Protein citrullination, a once-obscure post-translational modification (PTM) of peptidylarginine, has recently become an area of significant interest because of its suspected role in human disease states, including rheumatoid arthritis and multiple sclerosis, and also because of its newfound role in gene regulation.", "he increased levels of citrullinated CNS proteins associated with MS are also observed during the development of EAE. ", "Rheumatoid arthritis, multiple sclerosis, and Alzheimer's disease are examples of human diseases where protein citrullination involvement has been demonstrated", "citrullinated proteins may become a useful marker for human neurodegenerative diseases." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/23701010", "http://www.ncbi.nlm.nih.gov/pubmed/20590842", "http://www.ncbi.nlm.nih.gov/pubmed/22505457", "http://www.ncbi.nlm.nih.gov/pubmed/20013286", "http://www.ncbi.nlm.nih.gov/pubmed/24081567", "http://www.ncbi.nlm.nih.gov/pubmed/23960723", "http://www.ncbi.nlm.nih.gov/pubmed/24298040", "http://www.ncbi.nlm.nih.gov/pubmed/17168521", "http://www.ncbi.nlm.nih.gov/pubmed/22560840", "http://www.ncbi.nlm.nih.gov/pubmed/20399192", "http://www.ncbi.nlm.nih.gov/pubmed/19830834", "http://www.ncbi.nlm.nih.gov/pubmed/18787103", "http://www.ncbi.nlm.nih.gov/pubmed/23856045", "http://www.ncbi.nlm.nih.gov/pubmed/18576335", "http://www.ncbi.nlm.nih.gov/pubmed/23828821", "http://www.ncbi.nlm.nih.gov/pubmed/23030787", "http://www.ncbi.nlm.nih.gov/pubmed/15704193", "http://www.ncbi.nlm.nih.gov/pubmed/23022892", "http://www.ncbi.nlm.nih.gov/pubmed/16730216", "http://www.ncbi.nlm.nih.gov/pubmed/23118341", "http://www.ncbi.nlm.nih.gov/pubmed/23576281", "http://www.ncbi.nlm.nih.gov/pubmed/16856138", "http://www.ncbi.nlm.nih.gov/pubmed/21136610" ]

[]

[ "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0018101", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0070613", "http://www.disease-ontology.org/api/metadata/DOID:4", "http://www.biosemantics.org/jochem#4275497", "http://www.biosemantics.org/jochem#4275495", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0016485", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D004194", "http://amigo.geneontology.org/cgi-bin/amigo/term_details?term=GO:0006417", "http://www.nlm.nih.gov/cgi/mesh/2014/MB_cgi?field=uid&exact=Find+Exact+Term&term=D002956" ]

[ "Commotio cordis is a term used to describe cases of blunt thoracic impact causing sudden death without structural damage of the heart" ]

[ "blunt thoracic impact causing sudden death" ]

[ "Commotio cordis is a rare type of blunt cardiac injury in which low impact chest trauma causes sudden cardiac arrest, usually occurs from being struck by a projectile during sports.", "Commotio cordis due to blunt trauma to the precordium is a rare cause of death in young athletes, occurring less frequently than all of the other athletics-related deaths. Commotio cordis is a term used to describe cases of blunt thoracic impact causing fatality without structural damage of the heart and internal organs. ", "Although blunt, nonpenetrating chest blows causing sudden cardiac death (commotio cordis) are often associated with competitive sports, dangers implicit in such blows can extend into many other life activities. ", "Sudden death following blunt chest trauma is a frightening occurrence known as 'commotio cordis' or 'concussion of the heart'.", "Commotio cordis is a term used to describe cases of blunt thoracic impact causing fatality without gross structural damage of the heart and internal organs. ", "Cardiac concussion, previously known as commotio cordis, occurs in structurally normal hearts without gross or microscopic injury to the myocardium, cardiac valves, or coronary arteries, as opposed to other sports-related deaths known to occur more frequently in structural or congenital heart disease. ", "Nonpenetrating cardiac injuries due to direct precordial blunt impacts are a commonly encountered phenomenon in medicolegal offices.", "less commonly occurring manifestation of nonpenetrating injury is a concussion of the heart (commotio cordis), often with dramatic physiological consequences but no morphologic cardiac injury. " ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/21699851", "http://www.ncbi.nlm.nih.gov/pubmed/14646469", "http://www.ncbi.nlm.nih.gov/pubmed/11048776", "http://www.ncbi.nlm.nih.gov/pubmed/11208236", "http://www.ncbi.nlm.nih.gov/pubmed/11334832", "http://www.ncbi.nlm.nih.gov/pubmed/17957272", "http://www.ncbi.nlm.nih.gov/pubmed/22869311", "http://www.ncbi.nlm.nih.gov/pubmed/15331287", "http://www.ncbi.nlm.nih.gov/pubmed/17229310", "http://www.ncbi.nlm.nih.gov/pubmed/23107651", "http://www.ncbi.nlm.nih.gov/pubmed/22816548", "http://www.ncbi.nlm.nih.gov/pubmed/10392228", "http://www.ncbi.nlm.nih.gov/pubmed/9930916", "http://www.ncbi.nlm.nih.gov/pubmed/10894918", "http://www.ncbi.nlm.nih.gov/pubmed/22027166", "http://www.ncbi.nlm.nih.gov/pubmed/15744544", "http://www.ncbi.nlm.nih.gov/pubmed/6496438", "http://www.ncbi.nlm.nih.gov/pubmed/9703576", "http://www.ncbi.nlm.nih.gov/pubmed/20086611", "http://www.ncbi.nlm.nih.gov/pubmed/11879111", "http://www.ncbi.nlm.nih.gov/pubmed/18691236", "http://www.ncbi.nlm.nih.gov/pubmed/10338239", "http://www.ncbi.nlm.nih.gov/pubmed/11555799", "http://www.ncbi.nlm.nih.gov/pubmed/10498299", "http://www.ncbi.nlm.nih.gov/pubmed/19749607" ]

[]

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

[ "Phthiriasis palpebrarum is a rare eyelid infestation caused by phthirus pubis." ]

[ "Pthirus pubis" ]

[ "Phthiriasis palpebrarum is an uncommon cause of blepharoconjunctivitis in which Pthirus pubis infest the eyelashes. We report a case of unilateral phthiriasis palpebrarum with crab louse. ", "BACKGROUND: Pediculosis capitis is a common parasitic infestation, whereas phthiriasis palpebrarum is an uncommon infection due to Phthirus pubis (pubic lice) inoculating the eyelashes and surrounding tissues of the eye. ", "Head lice typically do not infect the eyes, and given the different morphology of the lice on the patient's head and eyes, a diagnosis of phthiriasis palpebrarum was made. ", "P. pubis can cause pruritic eyelid margins or unusual blepharoconjunctivitis. We present a case of phthiriasis palpebrarum in a 4-year-old boy.", "INTRODUCTION: Phthiriasis palpebrarum is an ectoparasitosis in which Phthirus pubis infest the eyelashes.", "In all cases, the diagnosis of phthiriasis palpebrarum was confirmed by parasitological examination of eyelashes, which revealed the presence of adult and nit forms of Phthirus pubis.", " Based on the observation of numerous nits at the base of the eyelashes and the ectoparasite in the palpebral margin, a diagnosis of phthiriasis palpebrarum was made.", "Phthiriasis palpebrarum (lice infestation of palpabrae) is a rarely reported disorder and may present as blepharoconjuctivitis. ", "Phthiriasis palpebrarum (PP) is a rare eyelid infestation caused by phthirus pubis.", "Phthiriasis palpebrarum, caused by Phthirus pubis, is an uncommon cause of blepharoconjunctivitis; therefore, this condition is easily misdiagnosed", "Phthiriasis palpebrarum, caused by the phthirus pubis, is a rare cause of blepharoconjunctivitis, and is therefore often neglected", "Phthiriasis palpebrarum is an uncommon cause of blepharoconjunctivitis in which Pthirus pubis infest the eyelashes", "Phthiriasis palpebrarum is an unusual cause of blepharoconjunctivitis and may easily be overlooked because of the failure of physicians to recognize Phthirus pubis", "Phthiriasis palpebrarum (PP) is a rare eyelid infestation caused by phthirus pubis", "Phthiriasis palpebrarum, caused by the phthirus pubis, is a rare cause of blepharoconjunctivitis, and is therefore often neglected. ", "Phthiriasis palpebrarum is an infestation of the eyelashes caused by the louse Pthirus pubis (Linnaeus, 1758). ", "Phthiriasis palpebrarum, caused by Phthirus pubis, is an uncommon cause of blepharoconjunctivitis; therefore, this condition is easily misdiagnosed.", "Phthiriasis palpebrarum, caused by the phthirus pubis, is a rare cause of blepharoconjunctivitis, and is therefore often neglected.", "Phthiriasis palpebrarum is an uncommon cause of blepharoconjunctivitis in which Pthirus pubis infest the eyelashes. We report a case of unilateral phthiriasis palpebrarum with crab louse.", "Phthiriasis palpebrarum is an infestation of the eyelashes caused by the louse Pthirus pubis (Linnaeus, 1758). We report a case of phthiriasis palpebrarum in a 6-year-old girl, which was initially misdiagnosed as allergic blepharoconjunctivitis.", "Phthiriasis palpebrarum is an unusual cause of blepharoconjunctivitis and may easily be overlooked because of the failure of physicians to recognize Phthirus pubis." ]

[ "http://www.ncbi.nlm.nih.gov/pubmed/26451147", "http://www.ncbi.nlm.nih.gov/pubmed/20339456", "http://www.ncbi.nlm.nih.gov/pubmed/16903509", "http://www.ncbi.nlm.nih.gov/pubmed/12523816", "http://www.ncbi.nlm.nih.gov/pubmed/24909484", "http://www.ncbi.nlm.nih.gov/pubmed/19728949", "http://www.ncbi.nlm.nih.gov/pubmed/24556565", "http://www.ncbi.nlm.nih.gov/pubmed/22707338", "http://www.ncbi.nlm.nih.gov/pubmed/23993722", "http://www.ncbi.nlm.nih.gov/pubmed/12898406", "http://www.ncbi.nlm.nih.gov/pubmed/24157356" ]

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