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Pesquisa : G02.111.873.750 [Categoria DeCS]
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  1 / 21920 MEDLINE  
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[PMID]:29182684
[Au] Autor:Huo T; Canepa R; Sura A; Modave F; Gong Y
[Ad] Endereço:Department of Health Outcomes & Policy, College of Medicine, University of Florida, Gainesville, Florida, United States of America.
[Ti] Título:Colorectal cancer stages transcriptome analysis.
[So] Source:PLoS One;12(11):e0188697, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Colorectal cancer (CRC) is the third most common cancer and the second leading cause of cancer-related deaths in the United States. The purpose of this study was to evaluate the gene expression differences in different stages of CRC. Gene expression data on 433 CRC patient samples were obtained from The Cancer Genome Atlas (TCGA). Gene expression differences were evaluated across CRC stages using linear regression. Genes with p≤0.001 in expression differences were evaluated further in principal component analysis and genes with p≤0.0001 were evaluated further in gene set enrichment analysis. A total of 377 patients with gene expression data in 20,532 genes were included in the final analysis. The numbers of patients in stage I through IV were 59, 147, 116 and 55, respectively. NEK4 gene, which encodes for NIMA related kinase 4, was differentially expressed across the four stages of CRC. The stage I patients had the highest expression of NEK4 genes, while the stage IV patients had the lowest expressions (p = 9*10-6). Ten other genes (RNF34, HIST3H2BB, NUDT6, LRCh4, GLB1L, HIST2H4A, TMEM79, AMIGO2, C20orf135 and SPSB3) had p value of 0.0001 in the differential expression analysis. Principal component analysis indicated that the patients from the 4 clinical stages do not appear to have distinct gene expression pattern. Network-based and pathway-based gene set enrichment analyses showed that these 11 genes map to multiple pathways such as meiotic synapsis and packaging of telomere ends, etc. Ten of these 11 genes were linked to Gene Ontology terms such as nucleosome, DNA packaging complex and protein-DNA interactions. The protein complex-based gene set analysis showed that four genes were involved in H2AX complex II. This study identified a small number of genes that might be associated with clinical stages of CRC. Our analysis was not able to find a molecular basis for the current clinical staging for CRC based on the gene expression patterns.
[Mh] Termos MeSH primário: Neoplasias Colorretais/genética
Transcriptoma
[Mh] Termos MeSH secundário: Idoso
Feminino
Regulação Neoplásica da Expressão Gênica
Seres Humanos
Modelos Lineares
Masculino
Meia-Idade
Análise de Componente Principal
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Em] Mês de entrada:1712
[Cu] Atualização por classe:180311
[Lr] Data última revisão:
180311
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171129
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0188697


  2 / 21920 MEDLINE  
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[PMID]:29483849
[Au] Autor:Hu Q; Wang Q; Meng Y; Tian H; Xiao H
[Ad] Endereço:1Yangtze River Fisheries Research Institute, Chinese Academy of Fishery Sciences, Wuhan, Hubei 430223 China.
[Ti] Título:Comparative transcriptome reveal the potential adaptive evolutionary genes in .
[So] Source:Hereditas;155:18, 2018.
[Is] ISSN:1601-5223
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:To search the evidence of molecular evolution mechanism for aquatic and cave habitat in , the evolution analysis was carried out among several species transcriptome data. The transcriptome data of , and were obtained from the Genbank and reassembled except . The BLAST search of transcriptome data obtained 1244 single-copy orthologous genes among five species A phylogenetic tree showed to have the closest relationship to . Fourteen positively selected genes were detected in and group and fifteen in and group. Five genes were shared in the both groups which involved in the immune system, suggesting that adaptation to an aquatic and cave environment required rapid evolution of the immune system compared to and .
[Mh] Termos MeSH primário: Evolução Molecular
Filogenia
Transcriptoma
Urodelos/genética
[Mh] Termos MeSH secundário: Animais
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180309
[Lr] Data última revisão:
180309
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180228
[St] Status:MEDLINE
[do] DOI:10.1186/s41065-018-0056-6


  3 / 21920 MEDLINE  
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[PMID]:29425202
[Au] Autor:Du M; Li N; Niu B; Liu Y; You D; Jiang D; Ruan C; Qin Z; Song T; Wang W
[Ad] Endereço:Key Lab for Quality, Efficient Cultivation and Security Control of Crops in Colleges and University of Yunnan Province, Honghe University, Mengzi, Yunnan Province, P.R. China.
[Ti] Título:De novo transcriptome analysis of Bagarius yarrelli (Siluriformes: Sisoridae) and the search for potential SSR markers using RNA-Seq.
[So] Source:PLoS One;13(2):e0190343, 2018.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: The yellow sisorid catfish (Bagarius yarrelli) is a carnivorous freshwater fish that inhabits the Honghe River, Lanchangjiang River and Nujiang River of southern China and other Southeast Asian countries. However, the publicly available genomic data for B. yarrelli are limited. METHODOLOGY AND PRINCIPAL FINDINGS: Illumina Solexa paired-end technology produced 1,706,456 raw reads from muscle, liver and caudal fin tissues of B. yarrelli. Nearly 5 Gb of data were acquired, and de novo assembly generated 14,607 unigenes, with an N50 of 2006 bp. A total of 9093 unigenes showed significant similarities to known proteins in public databases: 4477 and 6391 of B. yarrelli unigenes were mapped to the Gene Ontology (GO) and Clusters of Orthologous Groups (COG) databases, respectively. Moreover, 9635 unigenes were assigned to 242 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. In addition, 8568 microsatellites (simple sequence repeats, SSRs) were detected, and 31 pairs of polymorphic primers were characterized using wild populations of B. yarrelli from the Nujiang River, Yunnan Province, China. CONCLUSION/SIGNIFICANCE: These sequences enrich the genomic resources for B. yarrelli and will benefit future investigations into the evolutionary and biological processes of this and related Bagarius species. The SSR markers developed in this study will facilitate construction of genetic maps, investigations of genetic structures and germplasm polymorphism assessments in B. yarrelli.
[Mh] Termos MeSH primário: Peixes-Gato/genética
Marcadores Genéticos
Análise de Sequência de RNA
Transcriptoma
[Mh] Termos MeSH secundário: Animais
Repetições de Microssatélites/genética
Fases de Leitura Aberta
Reação em Cadeia da Polimerase
Polimorfismo Genético
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Genetic Markers)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180309
[Lr] Data última revisão:
180309
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180210
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0190343


  4 / 21920 MEDLINE  
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[PMID]:29414690
[Au] Autor:Li X; Lin Z; Zhan X; Gao J; Sun L; Cao Y; Qiu H
[Ad] Endereço:Department of Endocrinology, First Affiliated Hospital Harbin Medical University, Harbin, Heilongjiang, PR China; Department of Pharmacology, The State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education, Harbin Medical Un
[Ti] Título:RNA-seq analysis of the transcriptome of the liver of cynomolgus monkeys with type 2 diabetes.
[So] Source:Gene;651:118-125, 2018 Apr 20.
[Is] ISSN:1879-0038
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Genetic and environmental factors such as high-fat diet are involved in the development of type 2 diabetes mellitus (T2DM). Cynomolgus monkey shares similar genetic makeup, tissue structures, physiology and metabolic function to human. This study aimed to establish T2DM model in cynomolgus monkey and compare expression profiles of hepatic genes and their associated pathways in normal cynomolgus monkeys and those with T2DM. We employed RNA-seq technique and identified 1451 differentially expressed genes (DEGs) with a false discovery rate (FDR) of 0.1% between normal and T2DM animals. KEGG pathway analysis revealed that DEGs were associated with 12 KEGG pathways (P < 0.05). Two of these pathways were associated with metabolism and five were related to immunity. Unexpected, we found ECM-receptor interaction pathway. In conclusion, our data suggest that three major pathways may be implicated in the development of T2DM, including steroid biosynthesis, immune response and ECM. Further characterization of these pathways may provide new targets for the prevention and therapy of T2DM.
[Mh] Termos MeSH primário: Diabetes Mellitus Tipo 2/veterinária
Fígado/metabolismo
Macaca fascicularis/genética
Doenças dos Macacos/genética
Transcriptoma
[Mh] Termos MeSH secundário: Animais
Diabetes Mellitus Experimental/genética
Diabetes Mellitus Tipo 2/genética
Diabetes Mellitus Tipo 2/imunologia
Diabetes Mellitus Tipo 2/metabolismo
Modelos Animais de Doenças
Ontologia Genética
Masculino
Redes e Vias Metabólicas
Doenças dos Macacos/imunologia
Doenças dos Macacos/metabolismo
Análise de Sequência de RNA
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180309
[Lr] Data última revisão:
180309
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180208
[St] Status:MEDLINE


  5 / 21920 MEDLINE  
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[PMID]:29408859
[Au] Autor:Liu H; Wang J; Li L; Han C; He H; Xu H
[Ad] Endereço:Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu, Sichuan, P.R. China.
[Ti] Título:Transcriptome analysis revealed the possible regulatory pathways initiating female geese broodiness within the hypothalamic-pituitary-gonadal axis.
[So] Source:PLoS One;13(2):e0191213, 2018.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Geese have the strongest tendency toward broodiness among all poultry. The mechanisms initiating broodiness within the goose hypothalamic-pituitary-gonadal axis (HPGA) are still unclear. Here, we reported the transcriptome differences between laying and initial nesting within the HPGA tissues of geese. We constructed a unigene database based on HPGA tissues and identified 128,148 unigenes, 100% of which have been annotated. By using Digital Gene Expression (DGE) sequencing, we screened 19, 110, 289, and 211 differentially expressed genes (DEGs) in the hypothalamus, pituitary gland, stroma ovarii, and follicles, respectively, between laying and nesting geese. Expression changes of hypocretin (HCRT) and pro-opiomelanocortin (POMC) in the hypothalamus of nesting geese may cause appetite reduction, which is possibly the first step and a prerequisite to initiate broodiness. In addition to prolactin (PRL), follicle-stimulating hormone (FSH) and luteinizing hormone (LH), genes including oxytocin-neurophysin (OXT), chordin-like protein 1 (CHRDL1) and growth hormone (GH), expressed in the pituitary gland, are new candidate molecules that may be involved in broodiness in geese. Heme oxygenase 1 (HMOX1) in the pituitary gland, the proto-oncogene c-Fos (FOS), heat shock protein 90-alpha (HSP90AA), and cyclin-dependent kinase 1 (CDK1) in the ovary that may consolidate and transduce signals regulating the HPGA during broodiness in geese.
[Mh] Termos MeSH primário: Gônadas/fisiologia
Sistema Hipotálamo-Hipofisário/fisiologia
Transcriptoma
[Mh] Termos MeSH secundário: Animais
Feminino
Gansos
Expressão Gênica
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180309
[Lr] Data última revisão:
180309
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180207
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0191213


  6 / 21920 MEDLINE  
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[PMID]:29378241
[Au] Autor:Zhang L; Wang MY; Li XP; Wang XT; Jia CL; Yang XZ; Feng RQ; Yuan ML
[Ad] Endereço:State Key Laboratory of Grassland Agro-Ecosystems, College of Pastoral Agricultural Science and Technology, Lanzhou University, Lanzhou, Gansu 730020, People's Republic of China.
[Ti] Título:A small set of differentially expressed genes was associated with two color morphs in natural populations of the pea aphid Acyrthosiphon pisum.
[So] Source:Gene;651:23-32, 2018 Apr 20.
[Is] ISSN:1879-0038
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Color polymorphism is an ecologically important trait, which is related to local adaptation and ecological speciation. The pea aphid Acyrthosiphon pisum shows color polymorphism: the red and green color morphs where differences in ecological adaptation have been observed. Here, we measured genome-wide gene expression profiles of two color morphs in natural populations of A. pisum to explore the genetic basis of differentiated ecological adaptation. The results showed that only 32 genes were significantly differentially expressed between the two morphs, of which 18 had functional annotations. Among them, 13 genes were up-regulated [e.g. genes encoding protoheme IX farnesyltransferase (LOC100570971), carotene dehydrogenase (tor) and V-type proton ATPase subunit B (LOC100169462)] and 5 genes were down-regulated in the red morph (e.g. genes encoding transcription factors and heat shock proteins). To assess the functional importance of these differentially expressed genes (DEGs), we selected three highly expressed DEGs (LOC100169462, LOC100570971 and tor) with functional annotations and analyzed their expression levels in the red morph under three low temperatures (1 °C, 4 °C, and 8 °C) for 24 h. These three DEGs showed an interesting expression response to the cold acclimating conditions which resulted in an obvious phenotypic change of the red individuals to be greenish variants. This study suggests a link between gene expressions and body color polymorphisms in the pea aphid and provides important clues for further studying molecular mechanisms of ecological adaptation in aphids.
[Mh] Termos MeSH primário: Afídeos/genética
Genes de Insetos
[Mh] Termos MeSH secundário: Animais
Temperatura Baixa
Regulação Enzimológica da Expressão Gênica
Ontologia Genética
Medicago sativa
Pigmentação/genética
Polimorfismo Genético
Reação em Cadeia da Polimerase em Tempo Real
Análise de Sequência de RNA
Transcriptoma
beta-Caroteno 15,15'-Mono-Oxigenase/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
EC 1.14.99.36 (beta-Carotene 15,15'-Monooxygenase)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180309
[Lr] Data última revisão:
180309
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180130
[St] Status:MEDLINE


  7 / 21920 MEDLINE  
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[PMID]:29377955
[Au] Autor:Gedling CR; Smith CM; LeMoine CMR; Cassone BJ
[Ad] Endereço:Department of Plant Pathology, The Ohio State University, Wooster, OH, United States of America.
[Ti] Título:The Mexican bean beetle (Epilachna varivestis) regurgitome and insights into beetle-borne virus specificity.
[So] Source:PLoS One;13(1):e0192003, 2018.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:For nearly 400 million years, insects and plants have been embattled in an evolutionary arms race. Insects have developed diverse feeding strategies and behaviors in an effort to circumvent and overcome an extensive collection of plant defense tactics. Sap-sucking insects often inject saliva into hosts plants, which contains a suite of effector proteins and even microbial communities that can alter the plant's defenses. Lacking salivary glands, leaf-feeding beetles represent an interesting group of phytophagous insects. Feeding beetles regurgitate onto leaf surfaces and it is thought that these oral secretions influence insect-plant interactions and even play a role in virus-vector specificity. Since the molecular and biological makeup of the regurgitant is virtually unknown, we carried out RNA sequencing and 16S rDNA analysis on a major soybean pest, Epilachna varivestis, to generate the first ever beetle "regurgitome" and characterize its microbiome. Interestingly, the regurgitant is comprised of a rich molecular assortment of genes encoding putative extracellular proteins involved in digestion, molting, immune defense, and detoxification. By carrying out plant inoculation assays, we reinforced the fundamental role of the regurgitant in beetle-borne virus specificity. Ultimately, these studies begin to characterize the importance of regurgitant in virus transmission and beetle-plant interactions.
[Mh] Termos MeSH primário: Coleópteros/metabolismo
[Mh] Termos MeSH secundário: Animais
Coleópteros/genética
Coleópteros/fisiologia
Coleópteros/virologia
Genes de Insetos
Transcriptoma
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180309
[Lr] Data última revisão:
180309
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180130
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0192003


  8 / 21920 MEDLINE  
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[PMID]:29373585
[Au] Autor:Espitia O; Chatelais M; Steenman M; Charrier C; Maurel B; Georges S; Houlgatte R; Verrecchia F; Ory B; Lamoureux F; Heymann D; Gouëffic Y; Quillard T
[Ad] Endereço:INSERM, UMR 1238, Nantes, France; Université de Nantes, Nantes Atlantique Universités, Laboratoire « Sarcome osseux et remodelage des tissus osseux calcifiés ¼, Faculté de Médecine, Nantes, France.
[Ti] Título:Implication of molecular vascular smooth muscle cell heterogeneity among arterial beds in arterial calcification.
[So] Source:PLoS One;13(1):e0191976, 2018.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Vascular calcification is a strong and independent predictive factor for cardiovascular complications and mortality. Our previous work identified important discrepancies in plaque composition and calcification types between carotid and femoral arteries. The objective of this study is to further characterize and understand the heterogeneity in vascular calcification among vascular beds, and to identify molecular mechanisms underlying this process. We established ECLAGEN biocollection that encompasses human atherosclerotic lesions and healthy arteries from different locations (abdominal, thoracic aorta, carotid, femoral, and infrapopliteal arteries) for histological, cell isolation, and transcriptomic analysis. Our results show that lesion composition differs between these locations. Femoral arteries are the most calcified arteries overall. They develop denser calcifications (sheet-like, nodule), and are highly susceptible to osteoid metaplasia. These discrepancies may derive from intrinsic differences between SMCs originating from these locations, as microarray analysis showed specific transcriptomic profiles between primary SMCs isolated from each arterial bed. These molecular differences translated into functional disparities. SMC from femoral arteries showed the highest propensity to mineralize due to an increase in basal TGFß signaling. Our results suggest that biological heterogeneity of resident vascular cells between arterial beds, reflected by our transcriptomic analysis, is critical in understanding plaque biology and calcification, and may have strong implications in vascular therapeutic approaches.
[Mh] Termos MeSH primário: Artérias/patologia
Calcinose/patologia
Músculo Liso Vascular/patologia
[Mh] Termos MeSH secundário: Diferenciação Celular
Células Cultivadas
Seres Humanos
Placa Aterosclerótica/patologia
Transcriptoma
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180309
[Lr] Data última revisão:
180309
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180127
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0191976


  9 / 21920 MEDLINE  
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[PMID]:29339161
[Au] Autor:El Nagar S; Zindy F; Moens C; Martin L; Plassard D; Roussel MF; Lamonerie T; Billon N
[Ad] Endereço:Université Côte d'Azur, CNRS, Inserm, iBV, Nice, France.
[Ti] Título:A new genetically engineered mouse model of choroid plexus carcinoma.
[So] Source:Biochem Biophys Res Commun;496(2):568-574, 2018 02 05.
[Is] ISSN:1090-2104
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Choroid plexus carcinomas (CPCs) are highly malignant brain tumours predominantly found in children and associated to poor prognosis. Improved therapy for these cancers would benefit from the generation of animal models. Here we have created a novel mouse CPC model by expressing a stabilised form of c-Myc (MycT58A) and inactivating Trp53 in the choroid plexus of newborn mice. This induced aberrant proliferation of choroid plexus epithelial cells, leading to aggressive tumour development and death within 150 days. Choroid plexus tumours occurred with a complete penetrance in all brain ventricles, with prevalence in the lateral and fourth ventricles. Histological and cellular analysis indicated that these tumours were CPCs resembling their human counterparts. Comparison of gene expression profiles of CPCs and non-neoplastic tissues revealed profound alterations in cell cycle regulation and DNA damage responses, suggesting that dysregulation of cell division and DNA checkpoint pathways may represent key vulnerabilities. This novel animal model of CPC provides an invaluable tool to elucidate the mechanism of CPC formation and to develop successful therapies against this devastating paediatric cancer.
[Mh] Termos MeSH primário: Carcinoma/genética
Carcinoma/patologia
Neoplasias do Plexo Corióideo/genética
Neoplasias do Plexo Corióideo/patologia
Plexo Corióideo/patologia
Proteínas Proto-Oncogênicas c-myc/genética
Proteína Supressora de Tumor p53/genética
[Mh] Termos MeSH secundário: Animais
Carcinogênese/genética
Carcinogênese/patologia
Proliferação Celular
Dano ao DNA
Modelos Animais de Doenças
Seres Humanos
Camundongos
Camundongos Transgênicos
Mutação
Transcriptoma
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Proto-Oncogene Proteins c-myc); 0 (Tumor Suppressor Protein p53)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180309
[Lr] Data última revisão:
180309
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180118
[St] Status:MEDLINE


  10 / 21920 MEDLINE  
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[PMID]:29216900
[Au] Autor:Ribas L; Vanezis K; Imués MA; Piferrer F
[Ad] Endereço:Institut de Ciències del Mar, Consejo Superior de Investigaciones Científicas (CSIC), Passeig Marítim, 37-45, 08003, Barcelona, Spain.
[Ti] Título:Treatment with a DNA methyltransferase inhibitor feminizes zebrafish and induces long-term expression changes in the gonads.
[So] Source:Epigenetics Chromatin;10(1):59, 2017 12 08.
[Is] ISSN:1756-8935
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: The role of epigenetic modifications such as DNA methylation during vertebrate sexual development is far from being clear. Using the zebrafish model, we tested the effects of one of the most common DNA methyltransferase (dnmt) inhibitor, 5-aza-2'-deoxycytidine (5-aza-dC), which is approved for the treatment of acute myeloid leukaemia and is under active investigation for the treatment of solid tumours. Several dose-response experiments were carried out during two periods, including not only the very first days of development (0-6 days post-fertilization, dpf), as done in previous studies, but also, and as a novelty, the period of gonadal development (10-30 dpf). RESULTS: Early treatment with 5-aza-dC altered embryonic development, delayed hatching and increased teratology and mortality, as expected. The most striking result, however, was an increase in the number of females, suggesting that alterations induced by 5-aza-dC treatment can affect sexual development as well. Results were confirmed when treatment coincided with gonadal development. In addition, we also found that the adult gonadal transcriptome of 5-aza-dC-exposed females included significant changes in the expression of key reproduction-related genes (e.g. cyp11a1, esr2b and figla), and that several pro-female-related pathways such as the Fanconi anaemia or the Wnt signalling pathways were downregulated. Furthermore, an overall inhibition of genes implicated in epigenetic regulatory mechanisms (e.g. dnmt1, dicer, cbx4) was also observed. CONCLUSIONS: Taken together, our results indicate that treatment with a DNA methylation inhibitor can also alter the sexual development in zebrafish, with permanent alterations of the adult gonadal transcriptome, at least in females. Our results show the importance of DNA methylation for proper control of sexual development, open new avenues for the potential control of sex ratios in fish (aquaculture, population control) and call attention to possibly hidden long-term effects of dnmt therapy when used, for example, in the treatment of prepuberal children affected by some types of cancer.
[Mh] Termos MeSH primário: Metilases de Modificação do DNA/antagonistas & inibidores
Inibidores Enzimáticos/farmacologia
Feminização/induzido quimicamente
Ovário/efeitos dos fármacos
Peixe-Zebra/embriologia
[Mh] Termos MeSH secundário: Animais
Azacitidina/análogos & derivados
Azacitidina/farmacologia
Relação Dose-Resposta a Droga
Feminino
Masculino
Ovário/metabolismo
Razão de Masculinidade
Transcriptoma
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Enzyme Inhibitors); 776B62CQ27 (decitabine); EC 2.1.1.- (DNA Modification Methylases); M801H13NRU (Azacitidine)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180310
[Lr] Data última revisão:
180310
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171209
[St] Status:MEDLINE
[do] DOI:10.1186/s13072-017-0168-7



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