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[PMID]:28456703
[Au] Autor:Bi W; Li B; Song J; Hong Y; Zhang X; Liu H; Lu H; Zhou T; Cao J
[Ad] Endereço:School of Laboratory Medicine and Life Science, Wenzhou Medical University, Wenzhou, Zhejiang Province, China.
[Ti] Título:Antimicrobial susceptibility and mechanisms of fosfomycin resistance in extended-spectrum ß-lactamase-producing Escherichia coli strains from urinary tract infections in Wenzhou, China.
[So] Source:Int J Antimicrob Agents;50(1):29-34, 2017 Jul.
[Is] ISSN:1872-7913
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Fosfomycin in combination with various antibiotics represents an excellent clinically efficacious regimen for the treatment of urinary tract infections (UTIs) caused by extended-spectrum ß-lactamase (ESBL)-producing Escherichia coli. Underlying mechanisms of fosfomycin resistance remain largely uncharacterised. To investigate the antibacterial efficacy of fosfomycin against ESBL-producing E. coli, 356 non-repetitive ESBL-producing E. coli clinical isolates were collected from urine specimens from patients with UTI in Wenzhou, China, from January 2011 to December 2015. Antimicrobial sensitivity testing indicated that 6.7% (24/356) of the ESBL-producing E. coli strains were resistant to fosfomycin. The fosA3 gene encoding a fosfomycin-modifying enzyme was detected in 20 isolates by PCR and sequencing, alone or in combination with other ESBL determinants. Conjugation experiments and Southern blotting demonstrated that 70% (14/20) of the fosA3-positive isolates possessed transferable plasmids (ca. 54.2 kb) co-harbouring the ESBL resistance gene bla and the fosfomycin resistance gene fosA3. Among the four fosfomycin-resistant fosA3-negative E. coli isolates, three contained amino acid substitutions (Ile28Asn and Phe30Leu in MurA and Leu297Phe in GlpT). The results indicate that presence of the fosA3 gene is the primary mechanism of fosfomycin resistance in ESBL-producing E. coli isolates in Wenzhou, China. In addition, a plasmid (ca. 54.2 kb) co-harbouring fosA3 and bla genes is horizontally transferable. Furthermore, a low degree of homology in the fosfomycin-resistant E. coli was confirmed using multilocus sequence typing (MLST), suggesting that there is no obvious phenomenon of clonal dissemination.
[Mh] Termos MeSH primário: Antibacterianos/farmacologia
Farmacorresistência Bacteriana
Infecções por Escherichia coli/microbiologia
Escherichia coli/efeitos dos fármacos
Fosfomicina/farmacologia
Infecções Urinárias/microbiologia
beta-Lactamases/secreção
[Mh] Termos MeSH secundário: Southern Blotting
China
Conjugação Genética
Escherichia coli/enzimologia
Escherichia coli/isolamento & purificação
Proteínas de Escherichia coli/genética
Transferência Genética Horizontal
Seres Humanos
Testes de Sensibilidade Microbiana
Plasmídeos/análise
Reação em Cadeia da Polimerase
Análise de Sequência de DNA
beta-Lactamases/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anti-Bacterial Agents); 0 (Escherichia coli Proteins); 0 (FosA(3) protein, E coli); 2N81MY12TE (Fosfomycin); EC 3.5.2.6 (beta-Lactamases)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180222
[Lr] Data última revisão:
180222
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170501
[St] Status:MEDLINE


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[PMID]:28455331
[Au] Autor:Schötta AM; Wijnveld M; Stockinger H; Stanek G
[Ad] Endereço:Institute for Hygiene and Applied Immunology, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria anna-margarita.schoetta@meduniwien.ac.at.
[Ti] Título:Approaches for Reverse Line Blot-Based Detection of Microbial Pathogens in Ixodes ricinus Ticks Collected in Austria and Impact of the Chosen Method.
[So] Source:Appl Environ Microbiol;83(13), 2017 Jul 01.
[Is] ISSN:1098-5336
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Ticks transmit a large number of pathogens capable of causing human disease. In this study, the PCR-reverse line blot (RLB) method was used to screen for pathogens in a total of 554 ticks collected from all provinces of Austria. These pathogens belong to the genera , , / (including " Neoehrlichia"), , and The pathogens with the highest detected prevalence were spirochetes of the complex, in 142 ticks (25.6%). (80/142) was the most frequently detected species, followed by (38/142) and (36/142). , , and were found in 28 ticks, 5 ticks, and 1 tick, respectively. spp. were detected in 93 ticks (16.8%): (39/93), (38/93), (2/93), and (1/93). Thirteen samples remain uncharacterized. " Neoehrlichia mikurensis," spp. ( , , ), and were found in 4.5%, 2.7%, and 0.7%, respectively. was not detected. Multiple microorganisms were detected in 40 ticks (7.2%), and the cooccurrence of spp. and " Neoehrlichia mikurensis" showed a significant positive correlation. We also compared different PCR-RLBs for detection of and spp. and showed that different detection approaches provide highly diverse results, indicating that analysis of environmental samples remains challenging. This study determined the wide spectrum of tick-borne bacterial and protozoal pathogens that can be encountered in Austria. Surveillance of (putative) pathogenic microorganisms occurring in the environment is of medical importance, especially when those agents can be transmitted by ticks and cause disease. The observation of significant coinfections of certain microorganisms in field-collected ticks is an initial step to an improved understanding of microbial interactions in ticks. In addition, we show that variations in molecular detection methods, such as in primer pairs and target genes, can considerably influence the final results. For instance, detection of certain genospecies of borreliae may be better or worse by one method or the other, a fact of great importance for future screening studies.
[Mh] Termos MeSH primário: Anaplasma/isolamento & purificação
Southern Blotting/métodos
Borrelia/isolamento & purificação
Ixodes/microbiologia
Reação em Cadeia da Polimerase/métodos
Rickettsia/isolamento & purificação
[Mh] Termos MeSH secundário: Anaplasma/classificação
Anaplasma/genética
Animais
Áustria
Borrelia/classificação
Borrelia/genética
DNA Bacteriano/genética
Rickettsia/classificação
Rickettsia/genética
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (DNA, Bacterial)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:171225
[Lr] Data última revisão:
171225
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170430
[St] Status:MEDLINE


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[PMID]:28941610
[Au] Autor:Paquette M; Dufour R; Baass A
[Ad] Endereço:Nutrition, Metabolism, and Atherosclerosis Clinic, Institut de recherches cliniques de Montréal, Montréal, Québec, Canada.
[Ti] Título:Scavenger Receptor LOX1 Genotype Predicts Coronary Artery Disease in Patients With Familial Hypercholesterolemia.
[So] Source:Can J Cardiol;33(10):1312-1318, 2017 Oct.
[Is] ISSN:1916-7075
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Familial hypercholesterolemia (FH) is a monogenic disease associated with elevated low-density lipoprotein (LDL) cholesterol and oxidized LDL (oxLDL) leading to premature cardiovascular disease. Lectin-like oxLDL receptor-1 (LOX1) is one of the major contributors of oxLDL uptake and degradation in macrophages, which leads to foam cell formation and the development of atherosclerosis. This study investigated the effect of the rs11053646 genotype of the oxidized low-density lipoprotein receptor 1 (OLR1) gene on coronary artery disease (CAD) risk in a cohort of FH patients. METHODS: A total of 665 genetically confirmed heterozygous adult patients with FH were included in the analysis. We evaluated the association between the rs11053646 genotype (GG vs GC) and CAD. RESULTS: The GC genotype (K167N carriers) represented 12.9% of the study cohort (n = 86), whereas 87.1% of the participants were noncarriers (GG genotype) (n = 579). A significantly higher proportion of GC carriers experienced a CAD event (40.7%) than did GG carriers (29.0%; P = 0.03). The presence of a C allele remained significantly associated with an increased CAD risk, even when the regression model was corrected for all traditional CAD risk factors (odds ratio, 3.05; 95% confidence interval, 1.63-5.70; P = 0.0005). The negative impact of carrying the C allele on CAD risk was similar in both sexes but was significantly more important in smokers as well as in younger patients with FH. CONCLUSIONS: Carrying the C allele of the rs11053646 variant of the OLR1 gene was associated with an increased risk of CAD in heterozygous adult patients with FH, and this risk could be even greater in smokers as well as in younger patients.
[Mh] Termos MeSH primário: Doença da Artéria Coronariana/etiologia
DNA/genética
Hiperlipoproteinemia Tipo II/genética
Mutação
Receptores Depuradores Classe E/genética
[Mh] Termos MeSH secundário: Adulto
Alelos
Southern Blotting
Doença da Artéria Coronariana/sangue
Doença da Artéria Coronariana/diagnóstico
Análise Mutacional de DNA
Feminino
Genótipo
Heterozigoto
Seres Humanos
Hiperlipoproteinemia Tipo II/sangue
Hiperlipoproteinemia Tipo II/complicações
Masculino
Reação em Cadeia da Polimerase
Fatores de Risco
Receptores Depuradores Classe E/sangue
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (OLR1 protein, human); 0 (Scavenger Receptors, Class E); 9007-49-2 (DNA)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170929
[Lr] Data última revisão:
170929
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170925
[St] Status:MEDLINE


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[PMID]:28854735
[Au] Autor:Wang S; Pike AM; Lee SS; Strong MA; Connelly CJ; Greider CW
[Ad] Endereço:Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
[Ti] Título:BRD4 inhibitors block telomere elongation.
[So] Source:Nucleic Acids Res;45(14):8403-8410, 2017 Aug 21.
[Is] ISSN:1362-4962
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Cancer cells maintain telomere length equilibrium to avoid senescence and apoptosis induced by short telomeres, which trigger the DNA damage response. Limiting the potential for telomere maintenance in cancer cells has been long been proposed as a therapeutic target. Using an unbiased shRNA screen targeting known kinases, we identified bromodomain-containing protein 4 (BRD4) as a telomere length regulator. Four independent BRD4 inhibitors blocked telomere elongation, in a dose-dependent manner, in mouse cells overexpressing telomerase. Long-term treatment with BRD4 inhibitors caused telomere shortening in both mouse and human cells, suggesting BRD4 plays a role in telomere maintenance in vivo. Telomerase enzymatic activity was not directly affected by BRD4 inhibition. BRD4 is in clinical trials for a number of cancers, but its effects on telomere maintenance have not been previously investigated.
[Mh] Termos MeSH primário: Proteínas Nucleares/genética
Homeostase do Telômero/genética
Encurtamento do Telômero/genética
Fatores de Transcrição/genética
[Mh] Termos MeSH secundário: Acetanilidas/farmacologia
Animais
Azepinas/farmacologia
Southern Blotting
Linhagem Celular
Relação Dose-Resposta a Droga
Fibroblastos/citologia
Fibroblastos/efeitos dos fármacos
Fibroblastos/metabolismo
Expressão Gênica/efeitos dos fármacos
Células HeLa
Compostos Heterocíclicos com 3 Anéis/farmacologia
Compostos Heterocíclicos de 4 ou mais Anéis/farmacologia
Seres Humanos
Hibridização in Situ Fluorescente
Camundongos
Morfolinas/farmacologia
Proteínas Nucleares/antagonistas & inibidores
Proteínas Nucleares/metabolismo
Pironas/farmacologia
Interferência de RNA
Telomerase/genética
Telomerase/metabolismo
Telômero/efeitos dos fármacos
Telômero/enzimologia
Telômero/genética
Homeostase do Telômero/efeitos dos fármacos
Encurtamento do Telômero/efeitos dos fármacos
Fatores de Transcrição/antagonistas & inibidores
Fatores de Transcrição/metabolismo
Triazóis/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 ((+)-JQ1 compound); 0 (2-morpholin-4-yl-6-thianthren-1-yl-pyran-4-one); 0 (Acetanilides); 0 (Azepines); 0 (BRD4 protein, human); 0 (Brd4 protein, mouse); 0 (GSK1210151A); 0 (Heterocyclic Compounds, 3-Ring); 0 (Heterocyclic Compounds, 4 or More Rings); 0 (Morpholines); 0 (Nuclear Proteins); 0 (OTX015); 0 (Pyrones); 0 (Transcription Factors); 0 (Triazoles); EC 2.7.7.49 (Telomerase)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170901
[St] Status:MEDLINE
[do] DOI:10.1093/nar/gkx561


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[PMID]:28665990
[Au] Autor:Yamamoto K; Kawai-Toyooka H; Hamaji T; Tsuchikane Y; Mori T; Takahashi F; Sekimoto H; Ferris PJ; Nozaki H
[Ad] Endereço:Department of Biological Sciences, Graduate School of Science, the University of Tokyo, Bunkyo-ku, Tokyo, Japan.
[Ti] Título:Molecular evolutionary analysis of a gender-limited MID ortholog from the homothallic species Volvox africanus with male and monoecious spheroids.
[So] Source:PLoS One;12(6):e0180313, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Volvox is a very interesting oogamous organism that exhibits various types of sexuality and/or sexual spheroids depending upon species or strains. However, molecular bases of such sexual reproduction characteristics have not been studied in this genus. In the model species V. carteri, an ortholog of the minus mating type-determining or minus dominance gene (MID) of isogamous Chlamydomonas reinhardtii is male-specific and determines the sperm formation. Male and female genders are genetically determined (heterothallism) in V. carteri, whereas in several other species of Volvox both male and female gametes (sperm and eggs) are formed within the same clonal culture (homothallism). To resolve the molecular basis of the evolution of Volvox species with monoecious spheroids, we here describe a MID ortholog in the homothallic species V. africanus that produces both monoecious and male spheroids within a single clonal culture. Comparison of synonymous and nonsynonymous nucleotide substitutions in MID genes between V. africanus and heterothallic volvocacean species suggests that the MID gene of V. africanus evolved under the same degree of functional constraint as those of the heterothallic species. Based on semi quantitative reverse transcription polymerase chain reaction analyses using the asexual, male and monoecious spheroids isolated from a sexually induced V. africanus culture, the MID mRNA level was significantly upregulated in the male spheroids, but suppressed in the monoecious spheroids. These results suggest that the monoecious spheroid-specific down regulation of gene expression of the MID homolog correlates with the formation of both eggs and sperm in the same spheroid in V. africanus.
[Mh] Termos MeSH primário: Evolução Molecular
Genes de Plantas
Pólen
Esferoides Celulares
Volvox/genética
[Mh] Termos MeSH secundário: Southern Blotting
Óvulo Vegetal
Filogenia
Reação em Cadeia da Polimerase
Reprodução
Reação em Cadeia da Polimerase Via Transcriptase Reversa
Especificidade da Espécie
Volvox/classificação
Volvox/fisiologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171016
[Lr] Data última revisão:
171016
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170701
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0180313


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[PMID]:28553952
[Au] Autor:Gorman JA; Hundhausen C; Errett JS; Stone AE; Allenspach EJ; Ge Y; Arkatkar T; Clough C; Dai X; Khim S; Pestal K; Liggitt D; Cerosaletti K; Stetson DB; James RG; Oukka M; Concannon P; Gale M; Buckner JH; Rawlings DJ
[Ad] Endereço:Center for Immunity and Immunotherapies, Seattle Children's Research Institute, Seattle, Washington, USA.
[Ti] Título:The A946T variant of the RNA sensor IFIH1 mediates an interferon program that limits viral infection but increases the risk for autoimmunity.
[So] Source:Nat Immunol;18(7):744-752, 2017 Jul.
[Is] ISSN:1529-2916
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The single-nucleotide polymorphism rs1990760 in the gene encoding the cytosolic viral sensor IFIH1 results in an amino-acid change (A946T; IFIH1 ) that is associated with multiple autoimmune diseases. The effect of this polymorphism on both viral sensing and autoimmune pathogenesis remains poorly understood. Here we found that human peripheral blood mononuclear cells (PBMCs) and cell lines expressing the risk variant IFIH1 exhibited heightened basal and ligand-triggered production of type I interferons. Consistent with those findings, mice with a knock-in mutation encoding IFIH1 displayed enhanced basal expression of type I interferons, survived a lethal viral challenge and exhibited increased penetrance in autoimmune models, including a combinatorial effect with other risk variants. Furthermore, IFIH1 mice manifested an embryonic survival defect consistent with enhanced responsiveness to RNA self ligands. Together our data support a model wherein the production of type I interferons driven by an autoimmune risk variant and triggered by ligand functions to protect against viral challenge, which probably accounts for its selection within human populations but provides this advantage at the cost of modestly promoting the risk of autoimmunity.
[Mh] Termos MeSH primário: Autoimunidade/genética
Infecções por Cardiovirus/genética
Interferon Tipo I/imunologia
Helicase IFIH1 Induzida por Interferon/genética
[Mh] Termos MeSH secundário: Adolescente
Adulto
Animais
Doenças Autoimunes/genética
Doenças Autoimunes/imunologia
Autoimunidade/imunologia
Southern Blotting
Infecções por Cardiovirus/imunologia
Diabetes Mellitus Experimental/genética
Diabetes Mellitus Experimental/imunologia
Diabetes Mellitus Tipo 1/genética
Diabetes Mellitus Tipo 1/imunologia
Vírus da Encefalomiocardite/imunologia
Feminino
Predisposição Genética para Doença
Células HEK293
Seres Humanos
Immunoblotting
Helicase IFIH1 Induzida por Interferon/imunologia
Masculino
Camundongos
Meia-Idade
Polimorfismo de Nucleotídeo Único
Reação em Cadeia da Polimerase em Tempo Real
Reação em Cadeia da Polimerase Via Transcriptase Reversa
Viroses/genética
Viroses/imunologia
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Interferon Type I); EC 3.6.1.- (IFIH1 protein, human); EC 3.6.1.- (Ifih1 protein, mouse); EC 3.6.4.13 (Interferon-Induced Helicase, IFIH1)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:171123
[Lr] Data última revisão:
171123
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170530
[St] Status:MEDLINE
[do] DOI:10.1038/ni.3766


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[PMID]:28490008
[Au] Autor:Zhang X; Du J; Zhou C; Cao J; Lu H; Liu H; Bi W; Zhou T
[Ad] Endereço:Department of Clinical Laboratory, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
[Ti] Título:An Uncommon ST1224 NDM-1-Producing Klebsiella pneumoniae Isolated from the Bloodstream of a Leukemia Patient in China.
[So] Source:Chemotherapy;62(4):262-268, 2017.
[Is] ISSN:1421-9794
[Cp] País de publicação:Switzerland
[La] Idioma:eng
[Ab] Resumo:AIMS: This study aimed to analyze the clinical data and characteristics of an NDM-1 (New Delhi metallo-ß-lactamase-1)-producing Klebsiella pneumoniae isolated from the bloodstream of a leukemia patient. MATERIALS AND METHODS: A retrospective analysis was used for the clinical data of the patient. The modified Hodge test (MHT) and ethylenediaminetetraacetic acid (EDTA)-disk synergy test were used for detecting metallo-ß-lactamase. Antibiotic resistance was determined using the agar dilution method. PCR was used to identify resistance genes. S1-PFGE (S1 nuclease/pulsed-field gel electrophoresis) and Southern blot hybridization were performed to determine the location of blaNDM-1. A conjugation experiment was used to confirm the transferable characteristics of the resistant genes. Multilocus sequence typing (MLST) was also performed. RESULTS: The patient developed bloodstream infections caused by this NDM-1-producing strain and died due to worsening of the condition. The strain was highly resistant to ß-lactam antibiotics and coharbored blaNDM-1, qnrB, and blaCTX-M-9 genes. Southern blot confirmed that blaNDM-1 was located on a plasmid of approximately 55 kb and could be transferred to Escherichia coli J53. MLST analysis showed that this strain belonged to an uncommon sequence type ST1224. CONCLUSION: The coexistence of various resistant genes is the mechanism for resistance to most antibiotics. Additionally, infections caused by multi-drug resistant bacteria increase the mortality of patients with immunodeficiency, which alerts clinicians to establish a rational and effective combination drug therapy.
[Mh] Termos MeSH primário: Infecções por Klebsiella/diagnóstico
Klebsiella pneumoniae/enzimologia
Leucemia/diagnóstico
beta-Lactamases/metabolismo
[Mh] Termos MeSH secundário: Adolescente
Antibacterianos/farmacologia
Proteínas de Bactérias/genética
Proteínas de Bactérias/metabolismo
Southern Blotting
China
DNA Bacteriano/genética
DNA Bacteriano/metabolismo
Farmacorresistência Bacteriana Múltipla/genética
Eletroforese em Gel de Campo Pulsado
Feminino
Seres Humanos
Infecções por Klebsiella/complicações
Infecções por Klebsiella/microbiologia
Klebsiella pneumoniae/efeitos dos fármacos
Klebsiella pneumoniae/isolamento & purificação
Leucemia/complicações
Testes de Sensibilidade Microbiana
Tipagem de Sequências Multilocus
Plasmídeos/genética
Plasmídeos/metabolismo
Reação em Cadeia da Polimerase
Estudos Retrospectivos
beta-Lactamases/genética
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Anti-Bacterial Agents); 0 (Bacterial Proteins); 0 (DNA, Bacterial); EC 3.5.2.6 (beta-Lactamases); EC 3.5.2.6 (beta-lactamase NDM-1)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170908
[Lr] Data última revisão:
170908
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170511
[St] Status:MEDLINE
[do] DOI:10.1159/000469699


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[PMID]:28472655
[Au] Autor:García-González D; Khodosevich K; Watanabe Y; Rollenhagen A; Lübke JHR; Monyer H
[Ad] Endereço:Department of Clinical Neurobiology, Medical Faculty of Heidelberg University and German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany.
[Ti] Título:Serotonergic Projections Govern Postnatal Neuroblast Migration.
[So] Source:Neuron;94(3):534-549.e9, 2017 May 03.
[Is] ISSN:1097-4199
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:In many vertebrates, postnatally generated neurons often migrate long distances to reach their final destination, where they help shape local circuit activity. Concerted action of extrinsic stimuli is required to regulate long-distance migration. Some migratory principles are evolutionarily conserved, whereas others are species and cell type specific. Here we identified a serotonergic mechanism that governs migration of postnatally generated neurons in the mouse brain. Serotonergic axons originating from the raphe nuclei exhibit a conspicuous alignment with subventricular zone-derived neuroblasts. Optogenetic axonal activation provides functional evidence for serotonergic modulation of neuroblast migration. Furthermore, we show that the underlying mechanism involves serotonin receptor 3A (5HT3A)-mediated calcium influx. Thus, 5HT3A receptor deletion in neuroblasts impaired speed and directionality of migration and abolished calcium spikes. We speculate that serotonergic modulation of postnatally generated neuroblast migration is evolutionarily conserved as indicated by the presence of serotonergic axons in migratory paths in other vertebrates.
[Mh] Termos MeSH primário: Axônios/metabolismo
Encéfalo/crescimento & desenvolvimento
Cálcio/metabolismo
Movimento Celular/genética
Células-Tronco Neurais/metabolismo
Neurogênese/genética
Receptores 5-HT3 de Serotonina/genética
Neurônios Serotoninérgicos/metabolismo
[Mh] Termos MeSH secundário: Animais
Southern Blotting
Encéfalo/citologia
Encéfalo/metabolismo
Pré-Escolar
Tentilhões
Seres Humanos
Imuno-Histoquímica
Macaca mulatta
Masculino
Camundongos Knockout
Microscopia Confocal
Microscopia de Vídeo
Células-Tronco Neurais/citologia
Imagem Óptica
Optogenética
Coelhos
Núcleos da Rafe/citologia
Núcleos da Rafe/crescimento & desenvolvimento
Núcleos da Rafe/metabolismo
Receptores 5-HT3 de Serotonina/metabolismo
Neurônios Serotoninérgicos/citologia
Imagem com Lapso de Tempo
Peixe-Zebra
[Pt] Tipo de publicação:JOURNAL ARTICLE; VIDEO-AUDIO MEDIA
[Nm] Nome de substância:
0 (Htr3a protein, mouse); 0 (Receptors, Serotonin, 5-HT3); SY7Q814VUP (Calcium)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:170727
[Lr] Data última revisão:
170727
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170505
[St] Status:MEDLINE


  9 / 30093 MEDLINE  
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[PMID]:28362803
[Au] Autor:Won M; Dawid IB
[Ad] Endereço:Section on Developmental Biology, DDB, National Institute of Child Health and Human Development, NIH, Bethesda, Maryland, United States of America.
[Ti] Título:PCR artifact in testing for homologous recombination in genomic editing in zebrafish.
[So] Source:PLoS One;12(3):e0172802, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:We report a PCR-induced artifact in testing for homologous recombination in zebrafish. We attempted to replace the lnx2a gene with a donor cassette, mediated by a TALEN induced double stranded cut. The donor construct was flanked with homology arms of about 1 kb at the 5' and 3' ends. Injected embryos (G0) were raised and outcrossed to wild type fish. A fraction of the progeny appeared to have undergone the desired homologous recombination, as tested by PCR using primer pairs extending from genomic DNA outside the homology region to a site within the donor cassette. However, Southern blots revealed that no recombination had taken place. We conclude that recombination happened during PCR in vitro between the donor integrated elsewhere in the genome and the lnx2a locus. We conclude that PCR alone may be insufficient to verify homologous recombination in genome editing experiments in zebrafish.
[Mh] Termos MeSH primário: Peixe-Zebra/genética
[Mh] Termos MeSH secundário: Animais
Artefatos
Southern Blotting
Edição de Genes
Recombinação Homóloga/genética
Reação em Cadeia da Polimerase
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170828
[Lr] Data última revisão:
170828
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170401
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0172802


  10 / 30093 MEDLINE  
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[PMID]:28329327
[Au] Autor:Shadyab AH; LaMonte MJ; Kooperberg C; Reiner AP; Carty CL; Manini TM; Hou L; Di C; LaCroix AZ
[Ad] Endereço:Division of Epidemiology, Department of Family Medicine and Public Health, University of California, San Diego School of Medicine, La Jolla.
[Ti] Título:Association of Accelerometer-Measured Physical Activity With Leukocyte Telomere Length Among Older Women.
[So] Source:J Gerontol A Biol Sci Med Sci;72(11):1532-1537, 2017 Oct 12.
[Is] ISSN:1758-535X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Background: Previous studies on physical activity and telomere length have relied largely upon self-reported physical activity data, and few studies have examined older adults. The association of objectively measured physical activity with leukocyte telomere length (LTL) is currently unknown. Methods: In this study, we examined cross-sectional associations between accelerometer-measured total, light, and moderate-to-vigorous physical activity (MVPA) and LTL, measured using Southern blot. The sample included 1,405 older (64-95 years old) white and African American women from the Women's Health Initiative. Multiple linear regression models adjusting for potential confounders were used to determine the association between accelerometer-measured physical activity and LTL. Results: Overall, the mean (standard deviation) of total, light, and moderate-to-vigorous activity was 5.5 (1.6), 4.7 (1.3), and 0.8 (0.5) h/d, respectively. Adjusting for accelerometer wear time, age, race/ethnicity, education, marital status, smoking, alcohol, body mass index, a history of chronic diseases, and hormone therapy use, LTL was 80 (95% confidence interval: 9, 150) base pairs longer among women with ≥2.5 compared with <2.5 h/wk of MVPA. Light activity was not significantly associated with LTL. For total activity, the most physically active women had significantly longer LTL than the least active women after adjustment for demographic and lifestyle characteristics; however, findings were not significant after further adjustment for health-related factors. Conclusions: Older women meeting current recommendations of ≥2.5 h/wk of MVPA, as assessed by accelerometer, had longer LTL. Additional studies using accelerometers in large, diverse cohorts of older women are needed to confirm and extend these findings.
[Mh] Termos MeSH primário: Acelerometria/métodos
Envelhecimento/genética
Exercício/fisiologia
Telômero/genética
[Mh] Termos MeSH secundário: Afroamericanos
Idoso
Idoso de 80 Anos ou mais
Envelhecimento/etnologia
Southern Blotting
Estudos Transversais
Grupo com Ancestrais do Continente Europeu
Feminino
Seres Humanos
Leucócitos
Meia-Idade
Estados Unidos/epidemiologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171102
[Lr] Data última revisão:
171102
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170323
[St] Status:MEDLINE
[do] DOI:10.1093/gerona/glx037



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