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  1 / 22717 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


  2 / 22717 MEDLINE  
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[PMID]:29214789
[Au] Autor:Kim CW; Han JH; Wu L; Choi JY
[Ad] Endereço:Department of Otorhinolaryngology, Hallym University College of Medicine, Seoul, Korea.
[Ti] Título:microRNA-183 is Essential for Hair Cell Regeneration after Neomycin Injury in Zebrafish.
[So] Source:Yonsei Med J;59(1):141-147, 2018 Jan.
[Is] ISSN:1976-2437
[Cp] País de publicação:Korea (South)
[La] Idioma:eng
[Ab] Resumo:PURPOSE: microRNAs (miRNAs) are non-coding RNAs composed of 20 to 22 nucleotides that regulate development and differentiation in various organs by silencing specific RNAs and regulating gene expression. In the present study, we show that the microRNA (miR)-183 cluster is upregulated during hair cell regeneration and that its inhibition reduces hair cell regeneration following neomycin-induced ototoxicity in zebrafish. MATERIALS AND METHODS: miRNA expression patterns after neomycin exposure were analyzed using microarray chips. Quantitative polymerase chain reaction was performed to validate miR-183 cluster expression patterns following neomycin exposure (500 µM for 2 h). After injection of an antisense morpholino (MO) to miR-183 (MO-183) immediately after fertilization, hair cell regeneration after neomycin exposure in neuromast cells was evaluated by fluorescent staining (YO-PRO1). The MO-183 effect also was assessed in transgenic zebrafish larvae expressing green fluorescent protein (GFP) in inner ear hair cells. RESULTS: Microarray analysis clearly showed that the miR-183 cluster (miR-96, miR-182, and miR-183) was upregulated after neomycin treatment. We also confirmed upregulated expression of the miR-183 cluster during hair cell regeneration after neomycin-induced ototoxicity. miR-183 inhibition using MO-183 reduced hair cell regeneration in both wild-type and GFP transgenic zebrafish larvae. CONCLUSION: Our work demonstrates that the miR-183 cluster is essential for the regeneration of hair cells following ototoxic injury in zebrafish larvae. Therefore, regulation of the miR-183 cluster can be a novel target for stimulation of hair cell regeneration.
[Mh] Termos MeSH primário: Células Ciliadas Auditivas/fisiologia
MicroRNAs/metabolismo
Regeneração/genética
Peixe-Zebra/genética
[Mh] Termos MeSH secundário: Animais
Animais Geneticamente Modificados
Contagem de Células
Perfilação da Expressão Gênica
Regulação da Expressão Gênica/efeitos dos fármacos
Técnicas de Silenciamento de Genes
Proteínas de Fluorescência Verde/metabolismo
Células Ciliadas Auditivas/efeitos dos fármacos
Larva/efeitos dos fármacos
Larva/genética
MicroRNAs/genética
Morfolinos/farmacologia
Neomicina/toxicidade
Regeneração/efeitos dos fármacos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (MIRN183 microRNA, zebrafish); 0 (MicroRNAs); 0 (Morpholinos); 1404-04-2 (Neomycin); 147336-22-9 (Green Fluorescent Proteins)
[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:171208
[St] Status:MEDLINE
[do] DOI:10.3349/ymj.2018.59.1.141


  3 / 22717 MEDLINE  
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[PMID]:29357800
[Au] Autor:Siverio-Mota D; Andujar I; Marrero-Ponce Y; Giner RM; Diaz-Mendoza C; Paba GM; Vicet-Muro L; Cordero-Maldonado ML; de Witte PAM; Crawford AD; Veitia MS; Perez-Jimenez F; Aran VJ
[Ad] Endereço:Laboratory for Molecular Biodiscovery, Department of Pharmaceutical and Pharmacological Sciences, University of Leuven, Herestraat 49, 3000 Leuven, Belgium.
[Ti] Título:Anti-Inflammatory Activity and Cheminformatics Analysis of New Poten t 2-Substituted 1-Methyl-5-Nitroindazolinones.
[So] Source:Curr Top Med Chem;17(30):3236-3248, 2018 Feb 09.
[Is] ISSN:1873-4294
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:After the identification of the anti-inflammatory properties of VA5-13l (2-benzyl-1- methyl-5-nitroindazolinone) in previous investigations, some of its analogous compounds were designed, synthesized and evaluated in two anti-inflammatory methods: LPS-enhanced leukocyte migration assay in zebrafish; and 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced mouse ear edema. The products evaluated (3, 6, 8, 9 and 10) showed the lower values of relative leukocyte migration at 30 µM (0.14, 0.07, 0.10, 0.13 and 0.07, respectively), while in ear edema and myeloperoxidase activity methods, all the compounds reduced inflammation, only 4 and 16 yielded unsatisfactory results. The relationship linking structure and activity (SAR analysis) was determinate by using SARANEA software. The importance of the 5-Nitro group of the indazole ring for the activity was evident, and showed modest reduction when benzyl (Bn) is changed by alkyl group. A substituted Bn moiety at N2 (R) is the best substituent (5-10); nevertheless, if methylene group of Bn is deleted, the activity is affected. Also, introduction of halogen atoms mainly at positions 3 or 4 of the benzyl moiety (6 and 10) leads in general to strong activities. In fact, compounds 7 and 8 (R = 4-FBn or 4-ClBn, respectively) exhibit satisfactory results in in vivo tests and appear promising. The production of IL-6 at all doses assayed was significantly reduced, except with 16. Nonetheless, the production of TNF-α was significantly inhibited only by this chemical (16) at concentration of 50 µM. On the other hand, compound 2 was the one that mostly inhibited the expression of COX-2 and iNOS. From these results, it can be concluded that the inhibition in the release of cytokines can be one of the mechanisms of action responsible for the anti-inflammatory effect for 2-benzyl derivates while other 2-alkyl derivatives can inhibit production of NO. Therefore, nitroindazolinone chemical prototype could be an interesting structural group with anti-inflammatory purposes in the therapeutic.
[Mh] Termos MeSH primário: Anti-Inflamatórios não Esteroides/farmacologia
Inibidores de Ciclo-Oxigenase 2/farmacologia
Indazóis/farmacologia
Informática
Nitrocompostos/farmacologia
[Mh] Termos MeSH secundário: Animais
Anti-Inflamatórios não Esteroides/química
Ciclo-Oxigenase 2/metabolismo
Inibidores de Ciclo-Oxigenase 2/química
Relação Dose-Resposta a Droga
Seres Humanos
Indazóis/química
Lipopolissacarídeos/antagonistas & inibidores
Lipopolissacarídeos/farmacologia
Estrutura Molecular
Óxido Nítrico/antagonistas & inibidores
Óxido Nítrico/biossíntese
Óxido Nítrico Sintase Tipo II/antagonistas & inibidores
Óxido Nítrico Sintase Tipo II/metabolismo
Nitrocompostos/química
Relação Estrutura-Atividade
Fator de Necrose Tumoral alfa/antagonistas & inibidores
Peixe-Zebra
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Anti-Inflammatory Agents, Non-Steroidal); 0 (Cyclooxygenase 2 Inhibitors); 0 (Indazoles); 0 (Lipopolysaccharides); 0 (Nitro Compounds); 0 (Tumor Necrosis Factor-alpha); 31C4KY9ESH (Nitric Oxide); EC 1.14.13.39 (Nitric Oxide Synthase Type II); EC 1.14.99.1 (Cyclooxygenase 2)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180308
[Lr] Data última revisão:
180308
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180124
[St] Status:MEDLINE
[do] DOI:10.2174/1568026618666180119125255


  4 / 22717 MEDLINE  
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[PMID]:28946120
[Au] Autor:Zhao F; Jiang G; Wei P; Wang H; Ru S
[Ad] Endereço:Marine Life Science College, Ocean University of China, 5 Yushan Road, Qingdao, 266003 Shandong Province, PR China.
[Ti] Título:Bisphenol S exposure impairs glucose homeostasis in male zebrafish (Danio rerio).
[So] Source:Ecotoxicol Environ Saf;147:794-802, 2018 Jan.
[Is] ISSN:1090-2414
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Bisphenol S (BPS) is a substitute of the plastic additive bisphenol A (BPA). Its concentrations detected in surface waters and urine samples are on the same order of magnitude as BPA. Human exposure to BPA has been implicated in the development of diabetes mellitus; however, whether BPS can disrupt glucose homeostasis and increase blood glucose concentration remains unclear. We extensively investigated the effects of environmentally relevant concentrations of BPS on glucose metabolism in male zebrafish (Danio rerio) and the underlying mechanisms of these effects. Male zebrafish were exposed to 1, 10, or 100µg/L of BPS for 28 d. Fasting blood glucose (FBG) levels, glycogen levels in the liver and muscle, and mRNA levels of key glucose metabolic enzymes and the activities of the encoded proteins in tissues were evaluated to assess the effect of BPS on glucose metabolism. Plasma insulin levels and expression of preproinsulin and glucagon genes in the visceral tissue were also evaluated. Compared with the control group, exposure to 1 and 10µg/L of BPS significantly increased FBG levels but decreased insulin levels. Gluconeogenesis and glycogenolysis in the liver were promoted, and glycogen synthesis in the liver and muscle and glycolysis in the muscle were inhibited. Exposure to 100µg/L of BPS did not significantly alter plasma insulin and blood glucose levels, but nonetheless pronouncedly interfered with gluconeogenesis, glycogenolysis, glycolysis, and glycogen synthesis. Our data indicates that BPS at environmentally relevant concentrations impairs glucose homeostasis of male zebrafish possibly by hampering the physiological effect of insulin; higher BPS doses also pronouncedly interfered with glucose metabolism.
[Mh] Termos MeSH primário: Glucose/metabolismo
Homeostase/efeitos dos fármacos
Fenóis/toxicidade
Sulfonas/toxicidade
Poluentes Químicos da Água/toxicidade
Peixe-Zebra/metabolismo
[Mh] Termos MeSH secundário: Animais
Relação Dose-Resposta a Droga
Glucagon/genética
Glicogênio/biossíntese
Insulina/sangue
Insulina/genética
Fígado/efeitos dos fármacos
Fígado/metabolismo
Masculino
Músculos/efeitos dos fármacos
Músculos/metabolismo
Precursores de Proteínas/sangue
Precursores de Proteínas/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Insulin); 0 (Phenols); 0 (Protein Precursors); 0 (Sulfones); 0 (Water Pollutants, Chemical); 61116-24-3 (preproinsulin); 80-09-1 (bis(4-hydroxyphenyl)sulfone); 9005-79-2 (Glycogen); 9007-92-5 (Glucagon); IY9XDZ35W2 (Glucose)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180308
[Lr] Data última revisão:
180308
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170926
[St] Status:MEDLINE


  5 / 22717 MEDLINE  
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[PMID]:29382830
[Au] Autor:Aramillo Irizar P; Schäuble S; Esser D; Groth M; Frahm C; Priebe S; Baumgart M; Hartmann N; Marthandan S; Menzel U; Müller J; Schmidt S; Ast V; Caliebe A; König R; Krawczak M; Ristow M; Schuster S; Cellerino A; Diekmann S; Englert C; Hemmerich P; Sühnel J; Guthke R; Witte OW; Platzer M; Ruppin E; Kaleta C
[Ad] Endereço:Research Group Medical Systems Biology, Institute of Experimental Medicine, Christian-Albrechts-University Kiel, D-24105, Kiel, Germany.
[Ti] Título:Transcriptomic alterations during ageing reflect the shift from cancer to degenerative diseases in the elderly.
[So] Source:Nat Commun;9(1):327, 2018 01 30.
[Is] ISSN:2041-1723
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Disease epidemiology during ageing shows a transition from cancer to degenerative chronic disorders as dominant contributors to mortality in the old. Nevertheless, it has remained unclear to what extent molecular signatures of ageing reflect this phenomenon. Here we report on the identification of a conserved transcriptomic signature of ageing based on gene expression data from four vertebrate species across four tissues. We find that ageing-associated transcriptomic changes follow trajectories similar to the transcriptional alterations observed in degenerative ageing diseases but are in opposite direction to the transcriptomic alterations observed in cancer. We confirm the existence of a similar antagonism on the genomic level, where a majority of shared risk alleles which increase the risk of cancer decrease the risk of chronic degenerative disorders and vice versa. These results reveal a fundamental trade-off between cancer and degenerative ageing diseases that sheds light on the pronounced shift in their epidemiology during ageing.
[Mh] Termos MeSH primário: Envelhecimento/genética
Doenças Cardiovasculares/genética
Diabetes Mellitus/genética
Neoplasias/genética
Doenças Neurodegenerativas/genética
Transcriptoma
[Mh] Termos MeSH secundário: Adolescente
Adulto
Idoso
Idoso de 80 Anos ou mais
Envelhecimento/metabolismo
Envelhecimento/patologia
Animais
Encéfalo/crescimento & desenvolvimento
Encéfalo/metabolismo
Doenças Cardiovasculares/sangue
Doenças Cardiovasculares/patologia
Criança
Pré-Escolar
Doença Crônica
Diabetes Mellitus/sangue
Diabetes Mellitus/patologia
Fundulidae/genética
Fundulidae/crescimento & desenvolvimento
Fundulidae/metabolismo
Ontologia Genética
Genoma Humano
Seres Humanos
Lactente
Fígado/crescimento & desenvolvimento
Fígado/metabolismo
Camundongos
Meia-Idade
Anotação de Sequência Molecular
Neoplasias/metabolismo
Neoplasias/patologia
Doenças Neurodegenerativas/sangue
Doenças Neurodegenerativas/patologia
Pele/crescimento & desenvolvimento
Pele/metabolismo
Peixe-Zebra/genética
Peixe-Zebra/crescimento & desenvolvimento
Peixe-Zebra/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180307
[Lr] Data última revisão:
180307
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180201
[St] Status:MEDLINE
[do] DOI:10.1038/s41467-017-02395-2


  6 / 22717 MEDLINE  
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[PMID]:29382818
[Au] Autor:Sánchez-Iranzo H; Galardi-Castilla M; Minguillón C; Sanz-Morejón A; González-Rosa JM; Felker A; Ernst A; Guzmán-Martínez G; Mosimann C; Mercader N
[Ad] Endereço:Development of the Epicardium and Its Role during Regeneration Group, Centro Nacional de Investigaciones Cardiovasculares (CNIC-ISCIII), Melchor Fernández Almagro 3, 28029, Madrid, Spain.
[Ti] Título:Tbx5a lineage tracing shows cardiomyocyte plasticity during zebrafish heart regeneration.
[So] Source:Nat Commun;9(1):428, 2018 01 30.
[Is] ISSN:2041-1723
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:During development, mesodermal progenitors from the first heart field (FHF) form a primitive cardiac tube, to which progenitors from the second heart field (SHF) are added. The contribution of FHF and SHF progenitors to the adult zebrafish heart has not been studied to date. Here we find, using genetic tbx5a lineage tracing tools, that the ventricular myocardium in the adult zebrafish is mainly derived from tbx5a cells, with a small contribution from tbx5a SHF progenitors. Notably, ablation of ventricular tbx5a -derived cardiomyocytes in the embryo is compensated by expansion of SHF-derived cells. In the adult, tbx5a expression is restricted to the trabeculae and excluded from the outer cortical layer. tbx5a-lineage tracing revealed that trabecular cardiomyocytes can switch their fate and differentiate into cortical myocardium during adult heart regeneration. We conclude that a high degree of cardiomyocyte cell fate plasticity contributes to efficient regeneration.
[Mh] Termos MeSH primário: Ventrículos do Coração/citologia
Miocárdio/citologia
Miócitos Cardíacos/citologia
Regeneração/genética
Proteínas com Domínio T-Box/genética
Peixe-Zebra/genética
[Mh] Termos MeSH secundário: Animais
Animais Geneticamente Modificados
Diferenciação Celular
Linhagem da Célula/genética
Rastreamento de Células
Embrião não Mamífero
Regulação da Expressão Gênica no Desenvolvimento
Genes Reporter
Proteínas de Fluorescência Verde/genética
Proteínas de Fluorescência Verde/metabolismo
Ventrículos do Coração/crescimento & desenvolvimento
Ventrículos do Coração/metabolismo
Proteínas Luminescentes/genética
Proteínas Luminescentes/metabolismo
Miocárdio/metabolismo
Miócitos Cardíacos/metabolismo
Cadeias Leves de Miosina/genética
Cadeias Leves de Miosina/metabolismo
Organogênese/genética
Células-Tronco/citologia
Células-Tronco/metabolismo
Proteínas com Domínio T-Box/deficiência
Peixe-Zebra/crescimento & desenvolvimento
Peixe-Zebra/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Luminescent Proteins); 0 (Myosin Light Chains); 0 (T-Box Domain Proteins); 0 (T-box transcription factor 5); 0 (red fluorescent protein); 147336-22-9 (Green Fluorescent Proteins)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180307
[Lr] Data última revisão:
180307
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180201
[St] Status:MEDLINE
[do] DOI:10.1038/s41467-017-02650-6


  7 / 22717 MEDLINE  
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[PMID]:29335539
[Au] Autor:Eimon PM; Ghannad-Rezaie M; De Rienzo G; Allalou A; Wu Y; Gao M; Roy A; Skolnick J; Yanik MF
[Ad] Endereço:Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA, 02139, USA. peter.eimon@gmail.com.
[Ti] Título:Brain activity patterns in high-throughput electrophysiology screen predict both drug efficacies and side effects.
[So] Source:Nat Commun;9(1):219, 2018 01 15.
[Is] ISSN:2041-1723
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Neurological drugs are often associated with serious side effects, yet drug screens typically focus only on efficacy. We demonstrate a novel paradigm utilizing high-throughput in vivo electrophysiology and brain activity patterns (BAPs). A platform with high sensitivity records local field potentials (LFPs) simultaneously from many zebrafish larvae over extended periods. We show that BAPs from larvae experiencing epileptic seizures or drug-induced side effects have substantially reduced complexity (entropy), similar to reduced LFP complexity observed in Parkinson's disease. To determine whether drugs that enhance BAP complexity produces positive outcomes, we used light pulses to trigger seizures in a model of Dravet syndrome, an intractable genetic epilepsy. The highest-ranked compounds identified by BAP analysis exhibit far greater anti-seizure efficacy and fewer side effects during subsequent in-depth behavioral assessment. This high correlation with behavioral outcomes illustrates the power of brain activity pattern-based screens and identifies novel therapeutic candidates with minimal side effects.
[Mh] Termos MeSH primário: Encéfalo/fisiopatologia
Fenômenos Eletrofisiológicos
Psicotrópicos/farmacologia
Peixe-Zebra/fisiologia
[Mh] Termos MeSH secundário: Animais
Modelos Animais de Doenças
Eletrofisiologia/métodos
Epilepsias Mioclônicas/diagnóstico
Epilepsias Mioclônicas/fisiopatologia
Seres Humanos
Larva/efeitos dos fármacos
Larva/genética
Larva/fisiologia
Psicotrópicos/toxicidade
Peixe-Zebra/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Psychotropic Drugs)
[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:180117
[St] Status:MEDLINE
[do] DOI:10.1038/s41467-017-02404-4


  8 / 22717 MEDLINE  
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[PMID]:28972919
[Au] Autor:Liang YQ; Huang GY; Lin Z; Li J; Yang JW; Zhong LY; Ying GG
[Ad] Endereço:Faculty of Chemistry and Environmental Science, Guangdong Ocean University, Zhanjiang, 524088, PR China. Electronic address: liangyanqiu11@126.com.
[Ti] Título:Reproductive effects of synthetic progestin norgestrel in zebrafish (Danio rerio).
[So] Source:Chemosphere;190:17-24, 2018 Jan.
[Is] ISSN:1879-1298
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:The aim of this study was to assess the adverse effects of synthetic progestin norgestrel (NGT) on the reproduction of zebrafish by measuring the egg production, histology and transcriptional expression profiles along the hypothalamic-pituitary-gonadal (HPG) axis in adult zebrafish. After a pre-exposure period of 7 days, adult zebrafish were exposed to 6, 29 and 69 ng L NGT for 21 days. The results showed that exposure to 69 ng L NGT led to a significant up-regulation of follicle stimulating hormone, beta polypeptide (fshb), luteinizing hormone, beta polypeptide (lhb), progesterone receptor (pgr), estrogen receptor 1 (esr1) and androgen receptor (ar) genes in the brains, as well as significant up-regulation of hydroxysteroid 20-beta dehydrogenase (hsd20b) and hydroxysteroid 11-beta dehydrogenase 2 (hsd11b2) genes and down-regulation of 11-beta-hydroxylase (cyp11b) gene in the ovaries of females. In the testes of males, an overall down-regulation of steroidogenic acute regulatory protein (star), cytochrome P450-mediated side-chain cleavage enzyme (cyp11a1), cyp11b, hsd20b, hydroxysteroid 17-beta dehydrogenase type 3 (hsd17b3), hsd11b2 and ar genes were observed following exposure to different treatments of NGT. These transcriptional alterations imply that NGT could exhibit the potent progestogenic and androgenic activities in zebrafish. Egg production as well as histology in the ovaries and testes was not affected by NGT. Taken together, the overall results demonstrated that NGT could significantly affect transcriptional expression levels of genes related to HPG axis in zebrafish, and whether that change translates to additional physiological effects is needed further research.
[Mh] Termos MeSH primário: Regulação da Expressão Gênica/efeitos dos fármacos
Norgestrel/farmacologia
Reprodução/efeitos dos fármacos
Peixe-Zebra/fisiologia
[Mh] Termos MeSH secundário: Animais
Anticoncepcionais Orais Sintéticos/farmacologia
Feminino
Gonadotropinas Hipofisárias/genética
Hormônios Hipotalâmicos/genética
Masculino
Norgestrel/metabolismo
Progestinas/fisiologia
Receptores de Progesterona/genética
Peixe-Zebra/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Contraceptives, Oral, Synthetic); 0 (Gonadotropins, Pituitary); 0 (Hypothalamic Hormones); 0 (Progestins); 0 (Receptors, Progesterone); 3J8Q1747Z2 (Norgestrel)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180305
[Lr] Data última revisão:
180305
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171004
[St] Status:MEDLINE


  9 / 22717 MEDLINE  
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[PMID]:28463112
[Au] Autor:Edens BM; Yan J; Miller N; Deng HX; Siddique T; Ma YC
[Ad] Endereço:Department of Pediatrics, Northwestern University Feinberg School of Medicine, Ann & Robert H Lurie Children's Hospital of Chicago, Chicago, United States.
[Ti] Título:A novel ALS-associated variant in regulates motor axon morphogenesis.
[So] Source:Elife;6, 2017 05 02.
[Is] ISSN:2050-084X
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:The etiological underpinnings of amyotrophic lateral sclerosis (ALS) are complex and incompletely understood, although contributions to pathogenesis by regulators of proteolytic pathways have become increasingly apparent. Here, we present a novel variant in that is associated with ALS and show that its expression compromises motor axon morphogenesis in mouse motor neurons and in zebrafish. We further demonstrate that the ALS-associated variant impairs proteasomal function, and identify the Wnt signaling pathway effector beta-catenin as a substrate. Inhibition of beta-catenin function rescues the variant-induced motor axon phenotypes. These findings provide a strong link between the regulation of axonal morphogenesis and a new ALS-associated gene variant mediated by protein degradation pathways.
[Mh] Termos MeSH primário: Esclerose Amiotrófica Lateral/genética
Esclerose Amiotrófica Lateral/patologia
Proteínas de Transporte/genética
Morfogênese
Neurônios Motores/citologia
Proteínas Nucleares/genética
[Mh] Termos MeSH secundário: Animais
Modelos Animais de Doenças
Camundongos
Complexo de Endopeptidases do Proteassoma/metabolismo
Proteólise
Peixe-Zebra
beta Catenina/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T; RESEARCH SUPPORT, N.I.H., EXTRAMURAL
[Nm] Nome de substância:
0 (Carrier Proteins); 0 (Nuclear Proteins); 0 (UBQLN4 protein, human); 0 (beta Catenin); EC 3.4.25.1 (Proteasome Endopeptidase Complex)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180305
[Lr] Data última revisão:
180305
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170503
[St] Status:MEDLINE


  10 / 22717 MEDLINE  
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[PMID]:29227993
[Au] Autor:McGurk PD; Swartz ME; Chen JW; Galloway JL; Eberhart JK
[Ad] Endereço:Department of Molecular Biosciences, University of Texas at Austin, Austin, TX, United States of America.
[Ti] Título:In vivo zebrafish morphogenesis shows Cyp26b1 promotes tendon condensation and musculoskeletal patterning in the embryonic jaw.
[So] Source:PLoS Genet;13(12):e1007112, 2017 12.
[Is] ISSN:1553-7404
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Integrated development of diverse tissues gives rise to a functional, mobile vertebrate musculoskeletal system. However, the genetics and cellular interactions that drive the integration of muscle, tendon, and skeleton are poorly understood. In the vertebrate head, neural crest cells, from which cranial tendons derive, pattern developing muscles just as tendons have been shown to in limb and trunk tissue, yet the mechanisms of this patterning are unknown. From a forward genetic screen, we determined that cyp26b1 is critical for musculoskeletal integration in the ventral pharyngeal arches, particularly in the mandibulohyoid junction where first and second arch muscles interconnect. Using time-lapse confocal analyses, we detail musculoskeletal integration in wild-type and cyp26b1 mutant zebrafish. In wild-type fish, tenoblasts are present in apposition to elongating muscles and condense in discrete muscle attachment sites. In the absence of cyp26b1, tenoblasts are generated in normal numbers but fail to condense into nascent tendons within the ventral arches and, subsequently, muscles project into ectopic locales. These ectopic muscle fibers eventually associate with ectopic tendon marker expression. Genetic mosaic analysis demonstrates that neural crest cells require Cyp26b1 function for proper musculoskeletal development. Using an inhibitor, we find that Cyp26 function is required in a short time window that overlaps the dynamic window of tenoblast condensation. However, cyp26b1 expression is largely restricted to regions between tenoblast condensations during this time. Our results suggest that degradation of RA by this previously undescribed population of neural crest cells is critical to promote condensation of adjacent scxa-expressing tenoblasts and that these condensations are subsequently required for proper musculoskeletal integration.
[Mh] Termos MeSH primário: Desenvolvimento Embrionário/genética
Desenvolvimento Maxilofacial/genética
Morfogênese/genética
Ácido Retinoico 4 Hidroxilase/genética
[Mh] Termos MeSH secundário: Animais
Padronização Corporal/genética
Regulação da Expressão Gênica no Desenvolvimento
Arcada Osseodentária/embriologia
Desenvolvimento Muscular/genética
Músculo Esquelético/embriologia
Músculo Esquelético/metabolismo
Tendões/embriologia
Tendões/crescimento & desenvolvimento
Peixe-Zebra/embriologia
Peixe-Zebra/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL
[Nm] Nome de substância:
EC 1.14.14.1 (Retinoic Acid 4-Hydroxylase)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180305
[Lr] Data última revisão:
180305
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171212
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pgen.1007112



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