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[PMID]:29254927
[Au] Autor:Guangqi L; Congjiao S; Guiqin W; Fengying S; Aiqiao L; Hao S; Ning Y
[Ad] Endereço:1. College of Animal Science and Technology, China Agricultural University, Beijing 100193, China; 2. Beijing Huadu Yukou Poultry Industry Co. Ltd., Beijing 101206, China.
[Ti] Título:Transcriptome sequencing identifies potential regulatory genes involved in chicken eggshell brownness.
[So] Source:Yi Chuan;39(11):1102-1111, 2017 Nov 20.
[Is] ISSN:0253-9772
[Cp] País de publicação:China
[La] Idioma:eng
[Ab] Resumo:Brown eggs are popular in many countries, and consumers regard eggshell brownness as an important indicator of egg quality. Brown eggshell color is controlled by polygene. However, the responsible genes and detailed molecular mechanisms regulating eggshell brownness have not been defined. In the present study, we applied the RNA-seq technology to analyze the transcriptome data of the shell gland epithelium of hens and investigated the candidate genes associated with eggshell brownness. The results indicated that 8461 genes were expressed in the shell gland epithelium, of which 34 genes were differentially expressed in hens laying dark vs. light brown eggs. Functional analysis revealed that two genes, ovotransferrin (TF) and heat-shock protein 70 (HSP70), as well as the oxidative phosphorylation pathway were involved in the synthesis and transport of protoporphyrin â…¨, which might influence the formation of eggshell brownness and result in different shades of brown.
[Mh] Termos MeSH primário: Galinhas/genética
Casca de Ovo
Genes Reguladores/fisiologia
Transcriptoma
[Mh] Termos MeSH secundário: Animais
Cor
Conalbumina/fisiologia
Proteínas de Choque Térmico HSP70/fisiologia
Protoporfirinas/metabolismo
Análise de Sequência de RNA
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (HSP70 Heat-Shock Proteins); 0 (Protoporphyrins); 1391-06-6 (Conalbumin); C2K325S808 (protoporphyrin IX)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180306
[Lr] Data última revisão:
180306
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171220
[St] Status:MEDLINE
[do] DOI:10.16288/j.yczz.17-111


  2 / 10766 MEDLINE  
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[PMID]:29293518
[Au] Autor:Poggio L; González GE
[Ad] Endereço:Instituto de Ecología, Genética y Evolución (IEGEBA, Consejo Nacional de Investigaciones Científicas y Técnicas-CONICET)-Laboratorio de Citogenética y Evolución (LaCyE), Departamento de Ecología, Genética y Evolución, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad Autónoma de Buenos Aires, Argentina.
[Ti] Título:Cytological diploidization of paleopolyploid genus Zea: Divergence between homoeologous chromosomes or activity of pairing regulator genes?
[So] Source:PLoS One;13(1):e0189644, 2018.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Cytological diploidization process is different in autopolyploid and allopolyploid species. Colchicine applied at the onset of meiosis suppresses the effect of pairing regulator genes resulting multivalents formation in bivalent-forming species. Colchicine treated maizes (4x = 2n = 20, AmAmBmBm) showed up to 5IV, suggesting pairing between chromosomes from genomes homoeologous Am and Bm. In untreated individuals of the alloautooctoploid Zea perennis (8x = 2n = 40, ApApAp´Ap´Bp1Bp1Bp2Bp2) the most frequent configuration was 5IV+10II (formed by A and B genomes, respectively). The colchicine treated Z. perennis show up to 10IV revealing higher affinity within genomes A and B, but any homology among them. These results suggest the presence of a paring regulator locus (PrZ) in maize and Z. perennis, whose expression is suppressed by colchicine. It could be postulated that in Z. perennis, PrZ would affect independently the genomes A and B, being relevant the threshold of homology, the fidelity of pairing in each genomes and the ploidy level. Cytological analysis of the treated hexaploid hybrids (6x = 2n = 30), with Z. perennis as a parental, strongly suggests that PrZ is less effective in only one doses. This conclusion was reinforced by the homoeologous pairing observed in untreated dihaploid maizes, which showed up to 5II. Meiotic behaviour of individuals treated with different doses of colchicine allowed to postulate that PrZ affect the homoeologous association by controlling entire genomes (Am or Bm) rather than individual chromosomes. Based on cytological and statistical results it is possible to propose that the cytological diploidization in Zea species occurs by restriction of pairing between homoeologous chromosomes or by genetical divergence of the homoeologous chromosomes, as was observed in untreated Z. mays ssp. parviglumis. These are independent but complementary systems and could be acting jointly in the same nucleus.
[Mh] Termos MeSH primário: Cromossomos de Plantas
Diploide
Genes Reguladores
Zea mays/genética
[Mh] Termos MeSH secundário: Colchicina/administração & dosagem
Meiose
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
SML2Y3J35T (Colchicine)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180215
[Lr] Data última revisão:
180215
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180103
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0189644


  3 / 10766 MEDLINE  
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[PMID]:29272302
[Au] Autor:Zorenc Z; Veberic R; Slatnar A; Koron D; Miosic S; Chen MH; Haselmair-Gosch C; Halbwirth H; Mikulic-Petkovsek M
[Ad] Endereço:Department of Agronomy, Chair for Fruit, Wine and Vegetable Growing, Biotechnical Faculty, University of Ljubljana, Ljubljana, Slovenia.
[Ti] Título:A wild 'albino' bilberry (Vaccinium myrtillus L.) from Slovenia shows three bottlenecks in the anthocyanin pathway and significant differences in the expression of several regulatory genes compared to the common blue berry type.
[So] Source:PLoS One;12(12):e0190246, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Relative expressions of structural genes and a number of transcription factors of the anthocyanin pathway relevant in Vaccinium species, and related key enzyme activities were compared with the composition and content of metabolites in skins of ripe fruits of wild albino and blue bilberry (Vaccinium myrtillus) found in Slovenia. Compared to the common blue type, the albino variant had a 151-fold lower total anthocyanin and a 7-fold lower total phenolic content in their berry skin, which correlated with lower gene expression of flavonoid 3-O-glycosyltransferase (FGT; 33-fold), flavanone 3-hydroxylase (FHT; 18-fold), anthocyanidin synthase (ANS; 11-fold), chalcone synthase (CHS, 7.6-fold) and MYBPA1 transcription factor (22-fold). The expression of chalcone isomerase (CHI), dihydroflavonol 4-reductase (DFR), leucoanthocyanidin reductase (LAR), anthocyanidin reductase (ANR) and MYBC2 transcription factor was reduced only by a factor of 1.5-2 in the albino berry skins, while MYBR3 and flavonoid 3',5'-hydroxylase (F3'5'H) were increased to a similar extent. Expression of the SQUAMOSA class transcription factor TDR4, in contrast, was independent of the color type and does therefore not seem to be correlated with anthocyanin formation in this variant. At the level of enzymes, significantly lower FHT and DFR activities, but not of phenylalanine ammonia-lyase (PAL) and CHS/CHI, were observed in the fruit skins of albino bilberries. A strong increase in relative hydroxycinnamic acid derivative concentrations indicates the presence of an additional bottleneck in the general phenylpropanoid pathway at a so far unknown step between PAL and CHS.
[Mh] Termos MeSH primário: Antocianinas/metabolismo
Genes de Plantas
Genes Reguladores
Vaccinium myrtillus/metabolismo
[Mh] Termos MeSH secundário: Regulação da Expressão Gênica de Plantas
Fenóis/metabolismo
Eslovênia
Especificidade da Espécie
Vaccinium myrtillus/genética
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Anthocyanins); 0 (Phenols)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180116
[Lr] Data última revisão:
180116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171223
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0190246


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[PMID]:28977540
[Au] Autor:Ha M; Hong S
[Ad] Endereço:Samsung Advanced Institute of Technology, Samsung Electronics Corporation, Suwon 443-803, Korea.
[Ti] Título:Gene-regulatory interactions in embryonic stem cells represent cell-type specific gene regulatory programs.
[So] Source:Nucleic Acids Res;45(18):10428-10435, 2017 Oct 13.
[Is] ISSN:1362-4962
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Pluripotency, the ability of embryonic stem cells to differentiate into specialized cell types, is determined by ESC-specific gene regulators such as transcription factors and chromatin modification factors. It is not well understood how ESCs are poised for differentiation, however, and methods are needed for prognosis of the molecular changes in the differentiation of ESCs into specific organs. We describe a new approach to infer cell-type specific gene regulatory programs based on gene regulatory interactions in ESCs. Our method infers the molecular logic of gene regulatory mechanisms by mapping the position-specific combinatory patterns of numerous regulators in ESCs into cell-type specific gene regulations. We validate the proposed approach by recapitulating the RNA-seq and microarray data of neuronal progenitor cells, adult liver cells, and ESCs from the integrated patterns of diverse gene regulators in ESCs. We find that the collective functions of diverse gene regulators in ESCs represent distinct gene regulatory programs in specialized cell types. Our new approach expands our understanding of the differential gene regulatory information in developments encoded in regulatory networks of ESCs.
[Mh] Termos MeSH primário: Linhagem da Célula/genética
Regulação da Expressão Gênica
Redes Reguladoras de Genes/fisiologia
Células-Tronco Embrionárias Murinas/metabolismo
[Mh] Termos MeSH secundário: Animais
Diferenciação Celular/genética
Células Cultivadas
Genes Reguladores
Camundongos
Especificidade de Órgãos/genética
Regiões Promotoras Genéticas
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171031
[Lr] Data última revisão:
171031
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171005
[St] Status:MEDLINE
[do] DOI:10.1093/nar/gkx752


  5 / 10766 MEDLINE  
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[PMID]:28973452
[Au] Autor:Li B; Yue Y; Yuan Z; Zhang F; Li P; Song N; Lin W; Liu Y; Yang Y; Li Z; Gu L
[Ad] Endereço:Key Laboratory of Rare and Uncommon Diseases, Department of Microbiology, Institute of Basic Medicine, Shandong Academy of Medical Sciences, Jinan 250062, China.
[Ti] Título:Salmonella STM1697 coordinates flagella biogenesis and virulence by restricting flagellar master protein FlhD4C2 from recruiting RNA polymerase.
[So] Source:Nucleic Acids Res;45(17):9976-9989, 2017 Sep 29.
[Is] ISSN:1362-4962
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Salmonella reduces flagella biogenesis to avoid detection within host cells by a largely unknown mechanism. We identified an EAL-like protein STM1697 as required and sufficient for this process. STM1697 surges to a high level after Salmonella enters host cells and restrains the expression of flagellar genes by regulating the function of flagellar switch protein FlhD4C2, the transcription activator of all other flagellar genes. Unlike other anti-FlhD4C2 factors, STM1697 does not prevent FlhD4C2 from binding to target DNA. A 2.0 Å resolution STM1697-FlhD structure reveals that STM1697 binds the same region of FlhD as STM1344, but with weaker affinity. Further experiments show that STM1697 regulates flagella biogenesis by restricting FlhD4C2 from recruiting RNA polymerase and the regulatory effect of STM1697 on flagellar biogenesis and virulence are all achieved by interaction with FlhD. Finally, we describe a novel mechanism mediated by STM1697 in which Salmonella can inhibit the production of flagella antigen and escape from the host immune system.
[Mh] Termos MeSH primário: Proteínas de Bactérias/genética
RNA Polimerases Dirigidas por DNA/genética
Flagelos/metabolismo
Regulação Bacteriana da Expressão Gênica
Genes Reguladores
Genoma Bacteriano
Salmonella typhimurium/genética
[Mh] Termos MeSH secundário: Sequência de Aminoácidos
Animais
Proteínas de Bactérias/química
Proteínas de Bactérias/metabolismo
Sítios de Ligação
Clonagem Molecular
RNA Polimerases Dirigidas por DNA/metabolismo
Escherichia coli/genética
Escherichia coli/metabolismo
Feminino
Flagelos/ultraestrutura
Expressão Gênica
Macrófagos/microbiologia
Camundongos
Camundongos Endogâmicos BALB C
Modelos Moleculares
Biogênese de Organelas
Ligação Proteica
Domínios e Motivos de Interação entre Proteínas
Estrutura Secundária de Proteína
Proteínas Recombinantes/química
Proteínas Recombinantes/genética
Proteínas Recombinantes/metabolismo
Salmonella typhimurium/metabolismo
Salmonella typhimurium/patogenicidade
Alinhamento de Sequência
Homologia de Sequência de Aminoácidos
Virulência
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Bacterial Proteins); 0 (Recombinant Proteins); EC 2.7.7.6 (DNA-Directed RNA Polymerases)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171017
[Lr] Data última revisão:
171017
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171004
[St] Status:MEDLINE
[do] DOI:10.1093/nar/gkx656


  6 / 10766 MEDLINE  
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[PMID]:28911113
[Au] Autor:Bentham RB; Bryson K; Szabadkai G
[Ad] Endereço:Department of Cell and Developmental Biology, Consortium for Mitochondrial Research, University College London, London WC1E 6BT, UK.
[Ti] Título:MCbiclust: a novel algorithm to discover large-scale functionally related gene sets from massive transcriptomics data collections.
[So] Source:Nucleic Acids Res;45(15):8712-8730, 2017 Sep 06.
[Is] ISSN:1362-4962
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:The potential to understand fundamental biological processes from gene expression data has grown in parallel with the recent explosion of the size of data collections. However, to exploit this potential, novel analytical methods are required, capable of discovering large co-regulated gene networks. We found current methods limited in the size of correlated gene sets they could discover within biologically heterogeneous data collections, hampering the identification of multi-gene controlled fundamental cellular processes such as energy metabolism, organelle biogenesis and stress responses. Here we describe a novel biclustering algorithm called Massively Correlated Biclustering (MCbiclust) that selects samples and genes from large datasets with maximal correlated gene expression, allowing regulation of complex networks to be examined. The method has been evaluated using synthetic data and applied to large bacterial and cancer cell datasets. We show that the large biclusters discovered, so far elusive to identification by existing techniques, are biologically relevant and thus MCbiclust has great potential in the analysis of transcriptomics data to identify large-scale unknown effects hidden within the data. The identified massive biclusters can be used to develop improved transcriptomics based diagnosis tools for diseases caused by altered gene expression, or used for further network analysis to understand genotype-phenotype correlations.
[Mh] Termos MeSH primário: Algoritmos
Conjuntos de Dados como Assunto
Perfilação da Expressão Gênica
Redes Reguladoras de Genes/fisiologia
Sequenciamento de Nucleotídeos em Larga Escala
Neoplasias/genética
[Mh] Termos MeSH secundário: Análise por Conglomerados
Bases de Dados Genéticas
Perfilação da Expressão Gênica/métodos
Perfilação da Expressão Gênica/estatística & dados numéricos
Regulação da Expressão Gênica
Genes Reguladores
Estudos de Associação Genética/métodos
Estudos de Associação Genética/estatística & dados numéricos
Sequenciamento de Nucleotídeos em Larga Escala/métodos
Sequenciamento de Nucleotídeos em Larga Escala/estatística & dados numéricos
Seres Humanos
Análise de Sequência com Séries de Oligonucleotídeos/métodos
Análise de Sequência com Séries de Oligonucleotídeos/estatística & dados numéricos
Fenótipo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171107
[Lr] Data última revisão:
171107
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170916
[St] Status:MEDLINE
[do] DOI:10.1093/nar/gkx590


  7 / 10766 MEDLINE  
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Cohen, Moisés
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[PMID]:28902861
[Au] Autor:Leal MF; Caires Dos Santos L; Martins de Oliveira A; Santoro Belangero P; Antônio Figueiredo E; Cohen C; de Seixas Alves F; Hiromi Yanaguizawa W; Vicente Andreoli C; de Castro Pochini A; Ejnisman B; Cardoso Smith M; de Seixas Alves MT; Cohen M
[Ad] Endereço:Departamento de Ortopedia e Traumatologia, Universidade Federal de São Paulo, São Paulo, SP, Brazil.
[Ti] Título:Epigenetic regulation of metalloproteinases and their inhibitors in rotator cuff tears.
[So] Source:PLoS One;12(9):e0184141, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Rotator cuff tear is a common orthopedic condition. Metalloproteinases (MMP) and their inhibitors (TIMP) seem to play a role in the development of joint injuries and in the failure of tissue healing. However, the mechanisms of regulation of gene expression in tendons are still unknown. Epigenetic mechanisms, such as DNA methylation and microRNAs regulation, are involved in the dynamic control of gene expression. Here, the mRNA expression and DNA methylation status of MMPs (MMP1, MMP2, MMP3, MMP9, MMP13, and MMP14) and TIMPs (TIMP1-3) and the expression of miR-29 family members in ruptured supraspinatus tendons were compared with non-injured tendons of individuals without this lesion. Additionally, the gene expression and methylation status at the edge of the ruptured tendon were compared with macroscopically non-injured rotator cuff tendon samples from the anterior and posterior regions of patients with tendon tears. Moreover, the possible associations between the molecular alterations and the clinical and histologic characteristics were investigated. Dysregulated expression and DNA methylation of MMP and TIMP genes were found across the rotator cuff tendon samples of patients with supraspinatus tears. These alterations were influenced at least in part by age at surgery, sex, smoking habit, tear size, and duration of symptoms. Alterations in the studied MMP and TIMP genes may contribute to the presence of microcysts, fissures, necrosis, and neovascularization in tendons and may thus be involved in the tendon healing process. In conclusion, MMPs and their inhibitors are regulated by epigenetic modifications and may play a role in rotator cuff tears.
[Mh] Termos MeSH primário: Epigênese Genética
Genes Reguladores
Metaloproteases/genética
Lesões do Manguito Rotador/genética
Inibidores Teciduais de Metaloproteinases/genética
[Mh] Termos MeSH secundário: Adulto
Idoso
Estudos de Casos e Controles
Metilação de DNA
Feminino
Regulação Enzimológica da Expressão Gênica
Seres Humanos
Masculino
Meia-Idade
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Tissue Inhibitor of Metalloproteinases); EC 3.4.- (Metalloproteases)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171031
[Lr] Data última revisão:
171031
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170914
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0184141


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[PMID]:28892060
[Au] Autor:Peters LA; Perrigoue J; Mortha A; Iuga A; Song WM; Neiman EM; Llewellyn SR; Di Narzo A; Kidd BA; Telesco SE; Zhao Y; Stojmirovic A; Sendecki J; Shameer K; Miotto R; Losic B; Shah H; Lee E; Wang M; Faith JJ; Kasarskis A; Brodmerkel C; Curran M; Das A; Friedman JR; Fukui Y; Humphrey MB; Iritani BM; Sibinga N; Tarrant TK; Argmann C; Hao K; Roussos P; Zhu J; Zhang B; Dobrin R; Mayer LF; Schadt EE
[Ad] Endereço:Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
[Ti] Título:A functional genomics predictive network model identifies regulators of inflammatory bowel disease.
[So] Source:Nat Genet;49(10):1437-1449, 2017 Oct.
[Is] ISSN:1546-1718
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:A major challenge in inflammatory bowel disease (IBD) is the integration of diverse IBD data sets to construct predictive models of IBD. We present a predictive model of the immune component of IBD that informs causal relationships among loci previously linked to IBD through genome-wide association studies (GWAS) using functional and regulatory annotations that relate to the cells, tissues, and pathophysiology of IBD. Our model consists of individual networks constructed using molecular data generated from intestinal samples isolated from three populations of patients with IBD at different stages of disease. We performed key driver analysis to identify genes predicted to modulate network regulatory states associated with IBD, prioritizing and prospectively validating 12 of the top key drivers experimentally. This validated key driver set not only introduces new regulators of processes central to IBD but also provides the integrated circuits of genetic, molecular, and clinical traits that can be directly queried to interrogate and refine the regulatory framework defining IBD.
[Mh] Termos MeSH primário: Redes Reguladoras de Genes
Genes Reguladores
Genômica/métodos
Doenças Inflamatórias Intestinais/genética
Modelos Genéticos
[Mh] Termos MeSH secundário: Transferência Adotiva
Animais
Causalidade
Células Cultivadas
Colite/induzido quimicamente
Colite/genética
Conjuntos de Dados como Assunto
Modelos Animais de Doenças
Feminino
Técnicas de Silenciamento de Genes
Predisposição Genética para Doença
Estudo de Associação Genômica Ampla
Seres Humanos
Intestinos/metabolismo
Macrófagos/metabolismo
Masculino
Camundongos
Camundongos Endogâmicos C57BL
Camundongos Knockout
RNA Interferente Pequeno/genética
Subpopulações de Linfócitos T/transplante
Transcriptoma
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (RNA, Small Interfering)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171030
[Lr] Data última revisão:
171030
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170912
[St] Status:MEDLINE
[do] DOI:10.1038/ng.3947


  9 / 10766 MEDLINE  
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[PMID]:28827216
[Au] Autor:Chen Q; Ng V; Warfel JM; Merkel TJ; Stibitz S
[Ad] Endereço:Division of Bacterial, Parasitic, and Allergenic Products, Center for Biologics Evaluation and Research, FDA, Silver Spring, Maryland, USA qing.chen@fda.hhs.gov.
[Ti] Título:Activation of Bvg-Repressed Genes in Bordetella pertussis by RisA Requires Cross Talk from Noncooperonic Histidine Kinase RisK.
[So] Source:J Bacteriol;199(22), 2017 Nov 15.
[Is] ISSN:1098-5530
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The two-component response regulator RisA, encoded by open reading frame BP3554 in the Tohama I genomic sequence, is a known activator of genes, a set of genes whose expression is increased under the same environmental conditions (known as modulation) that result in repression of the virulence regulon. Here we demonstrate that RisA is phosphorylated and that RisA phosphorylation is required for activation of genes. An adjacent histidine kinase gene, , is truncated by frameshift mutation in but not in or Neither deletion of ' or nor phenotypic modulation with MgSO affected levels of phosphorylated RisA (RisA∼P) in However, RisA phosphorylation did require the histidine kinase encoded by BP3223, here named RisK (cognate histidine kinase of RisA). RisK was also required for expression of the genes. This requirement could be obviated by the introduction of the phosphorylation-mimicking RisA mutant, indicating that an active conformation of RisA, but not phosphorylation , is crucial for activation. Interestingly, expression of genes is still modulated by MgSO in cells harboring the RisA mutation, suggesting that the activated RisA senses additional signals to control expression in response to environmental stimuli. In , the BvgAS two-component system activates the expression of virulence genes by binding of BvgA∼P to their promoters. Expression of the reciprocally regulated genes requires RisA and is also repressed by the Bvg-activated BvgR. RisA is an OmpR-like response regulator, but RisA phosphorylation was not expected because the gene for its presumed, cooperonic, histidine kinase is inactivated by mutation. In this study, we demonstrate phosphorylation of RisA by a noncooperonic histidine kinase. We also show that RisA phosphorylation is necessary but not sufficient for activation but, importantly, is not affected by BvgAS status. Instead, we propose that expression is controlled by BvgAS through its regulation of BvgR, a cyclic di-GMP (c-di-GMP) phosphodiesterase.
[Mh] Termos MeSH primário: Proteínas de Bactérias/genética
Proteínas de Bactérias/metabolismo
Bordetella pertussis/genética
Regulação Bacteriana da Expressão Gênica
Receptores de Superfície Celular/genética
Receptores de Superfície Celular/metabolismo
Transativadores/metabolismo
[Mh] Termos MeSH secundário: Bordetella bronchiseptica/genética
Bordetella pertussis/metabolismo
Bordetella pertussis/patogenicidade
Mutação da Fase de Leitura
Genes Reguladores
Histidina Quinase/metabolismo
Sulfato de Magnésio/metabolismo
Mutação
Fosforilação
Regiões Promotoras Genéticas
Regulon
Transdução de Sinais
Transativadores/genética
Virulência
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Bacterial Proteins); 0 (Bvg accessory factor protein, Bordetella pertussis); 0 (Receptors, Cell Surface); 0 (RisA protein, Bordetella); 0 (Trans-Activators); 0 (vrg protein, Bordetella pertussis); 7487-88-9 (Magnesium Sulfate); EC 2.7.13.1 (Histidine Kinase)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171030
[Lr] Data última revisão:
171030
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170823
[St] Status:MEDLINE


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[PMID]:28628607
[Au] Autor:Krishnananthasivam S; Jayathilaka N; Sathkumara HD; Corea E; Natesan M; De Silva AD
[Ad] Endereço:Genetech Research Institute, Colombo, Sri Lanka.
[Ti] Título:Host gene expression analysis in Sri Lankan melioidosis patients.
[So] Source:PLoS Negl Trop Dis;11(6):e0005643, 2017 Jun.
[Is] ISSN:1935-2735
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Melioidosis is a life threatening infectious disease caused by the gram-negative bacillus Burkholderia pseudomallei predominantly found in southeast Asia and northern Australia. Studying the host transcription profiles in response to infection is crucial for understanding disease pathogenesis and correlates of disease severity, which may help improve therapeutic intervention and survival. The aim of this study was to analyze gene expression levels of human host factors in melioidosis patients and establish useful correlation with disease biomarkers, compared to healthy individuals and patients with sepsis caused by other pathogens. METHODS: The study population consisted of 30 melioidosis cases, 10 healthy controls and 10 sepsis cases caused by other pathogens. Total RNA was extracted from peripheral blood mononuclear cells (PBMC's) of study subjects. Gene expression profiles of 25 gene targets including 19 immune response genes and 6 epigenetic factors were analyzed by real time quantitative polymerase chain reaction (RT-qPCR). PRINCIPAL FINDINGS: Inflammatory response genes; TLR4, late onset inflammatory mediator HMGB1, genes associated with antigen presentation; MICB, PSMB2, PSMB8, PSME2, epigenetic regulators; DNMT3B, HDAC1, HDAC2 were significantly down regulated, whereas the anti-inflammatory gene; IL4 was up regulated in melioidosis patients compared to sepsis cases caused by other pathogens. Septicaemic melioidosis cases showed significant down regulation of IL8 compared to sepsis cases caused by other pathogens. HMGB1, MICB, PSMB8, PSMB2, PSME2, HDAC1, HDAC2 and DNMT3B showed consistent down regulation of gene expression in melioidosis patients compared to other sepsis infection, irrespective of comorbidities such as diabetes, duration of clinical symptoms and antibiotic treatment. SIGNIFICANCE: Specific immune response genes and epigenetic regulators are differentially expressed among melioidosis patients and patients with sepsis caused by other pathogens. Therefore, these genes may serve as biomarkers for disease diagnosis to distinguish melioidosis from cases of sepsis due to other infections and therapeutic intervention for melioidosis.
[Mh] Termos MeSH primário: Perfilação da Expressão Gênica
Melioidose/patologia
[Mh] Termos MeSH secundário: Biomarcadores/análise
Diagnóstico Diferencial
Genes Reguladores
Seres Humanos
Fatores Imunológicos/genética
Melioidose/diagnóstico
Reação em Cadeia da Polimerase em Tempo Real
Sri Lanka
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Biomarkers); 0 (Immunologic Factors)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:170726
[Lr] Data última revisão:
170726
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170620
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pntd.0005643



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