980 resultados para 17-Hydroxysteroid Dehydrogenases -- analysis -- genetics


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Analysing public sentiment about future events, such as demonstration or parades, may provide valuable information while estimating the level of disruption and disorder during these events. Social media, such as Twitter or Facebook, provides views and opinions of users related to any public topics. Consequently, sentiment analysis of social media content may be of interest to different public sector organisations, especially in the security and law enforcement sector. In this paper we present a lexicon-based approach to sentiment analysis of Twitter content. The algorithm performs normalisation of the sentiment in an effort to provide intensity of the sentiment rather than positive/negative label. Following this, we evaluate an evidence-based combining function that supports the classification process in cases when positive and negative words co-occur in a tweet. Finally, we illustrate a case study examining the relation between sentiment of twitter posts related to English Defence League and the level of disorder during the EDL related events.

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L’activation du système rénine-angiotensine-aldostérone peut entraîner le développement d’une hypertension artérielle et de la fibrose cardiaque. Toutefois, au cours de la grossesse, malgré une hausse substantielle des niveaux d’aldostérone, ces effets délétères ne sont pas observés. L’aldostérone exerce ses effets via les récepteurs des minéralocorticoïdes, les MR, qui peuvent également lier le cortisol avec une affinité similaire. La régulation des niveaux locaux de ce glucocorticoïde par les 11β-hydroxystéroïde déshydrogénases (11β-HSD) est donc essentielle pour éviter une stimulation inappropriée des MR. Nous suggérons que, durant la grossesse, ces enzymes sont impliquées dans la protection de la mère et du foetus contre les niveaux élevés d’aldostérone et de cortisol. Notre hypothèse de travail est que les mécanismes d’adaptation qui prennent place au cours de la grossesse nécessitent des changements d’expression (ARNm et protéine) et d’activité des 11β-HSD spécifiques selon le tissu. Des rates Sprague-Dawley ont été sacrifiées aux jours 14, 17, 19 et 22 de gestation (terme = jour 23) et leurs organes ont été collectés. Dans le rein, les niveaux protéiques des 11β-HSD sont diminués en fin de gestation. Dans le placenta, on observe une importante chute de l’expression génique et protéique de la 11β-HSD1 au jour 17 tandis que la 11β-HSD2 y est augmentée. L’expression et l’activité de la 11β-HSD2 sont par la suite diminuées jusqu’à terme. Aucune différence significative n’est retrouvée dans le ventricule gauche cardiaque. En conclusion, nos résultats démontrent que la gestation est accompagnée d’importants changements dans le placenta, possiblement pour assurer un développement foetal adéquat, tandis que le rein et le coeur sont peu ou pas affectés. Des études plus approfondies sur l’expression des MR dans ces tissus nous aideront à mieux comprendre l’implication des 11β-HSD au fil de la gestation.

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Las reacciones alérgicas a medicamentos cutáneas severas (RAM) como el Síndrome Stevens Johnson (SJS) y la Necrólisis Epidérmica Tóxica (NET),caracterizadas por exantema, erosión de la piel y las membranas mucosas, flictenas, desprendimiento de la piel secundario a la muerte de queratinocitos y compromiso ocular. Son infrecuentes en la población pero con elevada morbi-mortalidad, se presentan luego de la administración de diferentes fármacos. En Asia se ha asociado el alelo HLA-B*15:02 como marcador genético para SJS. En Colombia no hay datos de la incidencia de estas RAM, ni de la relación con medicamentos específicos o potenciales y tampoco estudios de aproximación genómica de genes de susceptibilidad.

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Presenta una lista, ordenada por categorias, de los proyectos y programas de las agencias que auspician las actividades en ciencia y tecnologia en el Caribe, incluyendo los fondos en dolares aprobados para cada uno de ellos.

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The king weakfish (pescada-gó in Portuguese - Macrodon ancylodon (Sciaenidae), a demersal (bottom-feeding) species found in South America Atlantic coastal waters from the Gulf of Paria in Venezuela to Baia Blanca in Argentina, is an economically important species because of its abundance and wide acceptance by consumers. Because of its wide distribution this fish may be subject to geographic isolation and this may have resulted in distinct populations along its coastal range. Considering that this species represents an important economic resource, confirmation of whether M. ancylodon is a single species or there are different genetic stocks spread over its wide distribution would be an important contribution to conservation policies and population management of the king weakfish. To investigate differences between king weakfish populations we used the cytochrome b and 16S rRNA genes to characterize M. ancylodon specimens caught throughout its South American range from Venezuela to Argentina. Our results clearly distinguished two genetically different groups which show nucleotide divergence and genetic structuring patterns that strongly suggest they may be different species, disagreeing with the widely accepted traditional taxonomy that accepts only one species of Macrodon in the western Atlantic.

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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

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Synthetic corticosteroids are used widely for the treatment of a variety of diseases of the mouth. However, little is known as to whether the oral mucosa is able to modulate the local concentration of active corticosteroids or to produce steroids de novo. This has important clinical implications, because tissue-specific regulation of glucocorticoids is a key determinant of the clinical efficacy of these drugs. In the present study, we show that oral fibroblasts and keratinocytes expressed ACTH receptor (MC2R), glucocorticoid receptor (GR), and 11 beta-hydroxysteroid dehydrogenases (11 beta-HSDs). Unlike keratinocytes, fibroblasts lacked 11 beta-HSD2 and could not effectively deactivate exogenously administered cortisol. However, both cell types were able not only to activate cortisone into the active form cortisol, but also to synthesize cortisol de novo following stimulation with ACTH. 11 beta-HSD2, the enzyme controlling cortisol deactivation, exhibited different patterns of expression in normal (squamous epithelium and salivary glands) and diseased oral mucosa (squamous cell carcinoma and mucoepidermoid carcinoma). Blocking of endogenous cortisol catabolism in keratinocytes with the 11 beta-HSD2 inhibitor 18 beta-glycyrrhetinic acid mimicked the effect of exogenous administration of hydrocortisone and partially prevented the detrimental effects induced by pemphigus vulgaris sera. Analysis of the data demonstrates that a novel, non-adrenal glucocorticoid system is present in the oral mucosa that may play an important role in disease.

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Abstract Background Tachycardia is commonly observed in hypertensive patients, predominantly mediated by regulatory mechanisms integrated within the autonomic nervous system. The genetic loci and genes associated with increased heart rate in hypertension, however, have not yet been identified. Methods An F2 intercross of Spontaneously Hypertensive Rats (SHR) × Brown Norway (BN) linkage analysis of quantitative trait loci mapping was utilized to identify candidate genes associated with an increased heart rate in arterial hypertension. Results Basal heart rate in SHR was higher compared to that of normotensive BN rats (365 ± 3 vs. 314 ± 6 bpm, p < 0.05 for SHR and BN, respectively). A total genome scan identified one quantitative trait locus in a 6.78 cM interval on rat chromosome 8 (8q22–q24) that was responsible for elevated heart rate. This interval contained 241 genes, of which 65 are known genes. Conclusion Our data suggest that an influential genetic region located on the rat chromosome 8 contributes to the regulation of heart rate. Candidate genes that have previously been associated with tachycardia and/or hypertension were found within this QTL, strengthening our hypothesis that these genes are, potentially, associated with the increase in heart rate in a hypertension rat model.

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Glucocorticoid hormones, acting via nuclear receptors, regulate many metabolic processes, including hepatic gluconeogenesis. It recently has been recognized that intracellular glucocorticoid concentrations are determined not only by plasma hormone levels, but also by intracellular 11β-hydroxysteroid dehydrogenases (11β-HSDs), which interconvert active corticosterone (cortisol in humans) and inert 11-dehydrocorticosterone (cortisone in humans). 11β-HSD type 2, a dehydrogenase, thus excludes glucocorticoids from otherwise nonselective mineralocorticoid receptors in the kidney. Recent data suggest the type 1 isozyme (11β-HSD-1) may function as an 11β-reductase, regenerating active glucocorticoids from circulating inert 11-keto forms in specific tissues, notably the liver. To examine the importance of this enzyme isoform in vivo, mice were produced with targeted disruption of the 11β-HSD-1 gene. These mice were unable to convert inert 11-dehydrocorticosterone to corticosterone in vivo. Despite compensatory adrenal hyperplasia and increased adrenal secretion of corticosterone, on starvation homozygous mutants had attenuated activation of the key hepatic gluconeogenic enzymes glucose-6-phosphatase and phosphoenolpyruvate carboxykinase, presumably, because of relative intrahepatic glucocorticoid deficiency. The 11β-HSD-1 −/− mice were found to resist hyperglycamia provoked by obesity or stress. Attenuation of hepatic 11β-HSD-1 may provide a novel approach to the regulation of gluconeogenesis.

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Genes in the TGF9 signaling pathway play important roles in the regulation of ovarian follicle growth and ovulation rate. Mutations in three genes in this pathway, growth differentiation factor 9 (GDF9), bone morphogenetic protein 15 (BMP15) and the bone morphogenetic protein receptor B 1 (BMPRB1), influence dizygotic (DZ) twinning rates in sheep. To date, only variants in GDF9 and BMP15, but not their receptors transforming growth factor ss receptor 1 (TGFBR1), bone morphogenetic protein receptor 2 (BMPR2) and BMPR1B, have been investigated with respect to their roles in human DZ twinning. We screened for rare and novel variants in TGFBR1, BMPR2 and BMPR1B in mothers of dizygotic twins (MODZT) from twin-dense families, and assessed association between genotyped and imputed variants and DZ twinning in another large sample of MODZT. Three novel variants were found: a deep intronic variant in BMPR2, and one intronic and one non-synonymous exonic variant in BMPRB1 which would result in the replacement of glutamine by glutamic acid at amino acid position 294 (p.Gln294Glu). None of these variants were predicted to have major impacts on gene function. However, the p.Gln294Glu variant changes the same amino acid as a sheep BMPR1B functional variant and may have functional consequences. Six BMPR1B variants were marginally associated with DZ twinning in the larger case-control sample, but these were no longer significant once multiple testing was taken into account. Our results suggest that variation in the TGF9 signaling pathway type II receptors has limited effects on DZ twinning rates in humans.

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Regulated transcription controls the diversity, developmental pathways and spatial organization of the hundreds of cell types that make up a mammal. Using single-molecule cDNA sequencing, we mapped transcription start sites (TSSs) and their usage in human and mouse primary cells, cell lines and tissues to produce a comprehensive overview of mammalian gene expression across the human body. We find that few genes are truly 'housekeeping', whereas many mammalian promoters are composite entities composed of several closely separated TSSs, with independent cell-type-specific expression profiles. TSSs specific to different cell types evolve at different rates, whereas promoters of broadly expressed genes are the most conserved. Promoter-based expression analysis reveals key transcription factors defining cell states and links them to binding-site motifs. The functions of identified novel transcripts can be predicted by coexpression and sample ontology enrichment analyses. The functional annotation of the mammalian genome 5 (FANTOM5) project provides comprehensive expression profiles and functional annotation of mammalian cell-type-specific transcriptomes with wide applications in biomedical research.

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The immunolocalization and gene expression of vascular endothelial growth factor (VEGF) and its cognate tyrosine kinase receptors, Flt-1 and KDR, has been studied in ocular melanomas and retinoblastomas using in situ hybridization and immunohistochemistry. Tumour-related alterations in VEGF/VEGF-receptor expression have also been examined in separate and uninvolved iris, retina and choroid of the same eyes. Although VEGF immunoreactivity in the normal retina was virtually absent, low-level VEGF expression was evident in the ganglion cell-bodies, Müller cells and in a distinct population of amacrine cells. VEGF gene expression was absent in the iris and choroid of normal eyes. In tumour-bearing eyes, high levels of VEGF protein and gene expression were observed within the vascularized regions of the tumours, while the adjacent retina and choroid showed increased VEGF levels when compared with normals. Flt-1 and KDR gene expression and immunolocalization occurred in VEGF-expressing ganglion, Müller and amacrine cells in normal eyes. Within the intra-ocular tumours, VEGF-receptor gene expression and protein was evident in the endothelial cells and also in cells close to the vessels, while in the adjacent retina, Flt-1 and KDR levels were elevated over normal, especially in the blood vessels. Flt-1 and KDR were both observed at elevated levels in the choroid and iris blood vessels. This study suggests that VEGF, Flt-1 and KDR are expressed by neural, glial and vascular elements within normal human retina. Intra-ocular tumours demonstrate a high level of VEGF and VEGF-receptor expression; within uninvolved, spatially separate retina, choroid and iris in the same eyes, expression is also elevated, especially within the vasculature. Retinal vascular endothelia may respond to high intra-ocular levels of VEGF by increasing expression of their VEGF receptors, a phenomenon which could have relevance to neoplasm-related ocular neovascularization.

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A presente investigação procura compreender o fenómeno complexo e dinâmico que é a avaliação das aprendizagens das crianças em colaboração com a família na Educação Pré-Escolar (EPE) como forma de potenciar o desenvolvimento de competências pelas crianças. Assim, e recorrendo a um estudo de caso com uma componente de investigação-acção, pretende-se (i) compreender as concepções e práticas de avaliação de aprendizagens na EPE desenvolvidas por um grupo de educadores de uma Instituição Privada de Solidariedade Social da região centro do país e (ii) potenciar, através de formação em contexto que contemple o desenvolvimento de estratégias inerentes a uma avaliação das aprendizagens em colaboração com a família das crianças, o desenvolvimento profissional dos educadores de infância neste âmbito, proporcionando experiências educativas que levem as crianças a desenvolver um conjunto de competências inerentes à nova natureza dos saberes básicos de todos os cidadãos do séc. XXI. Tomando como ideias base da investigação a concepção (i) da criança enquanto cidadão (Prout, 2005; Vasconcelos, 2009) e (ii) da família enquanto primeira e principal educadora das crianças (Steves, Hough & Nurs, 2002), a investigação foi desenvolvida em quatro fases: Fase I – Formulação de um referencial de competências para a EPE inerentes à nova natureza dos saberes básicos do séc. XXI e seu processo de transferibilidade e credibilidade; Fase II – Diagnóstico das concepções dos participantes da investigação sobre avaliação das aprendizagens na EPE e colaboração Instituição/Família; Fase III – Construção e implementação de um programa de formação para educadores de infância; Fase IV – Avaliação do impacte do programa de formação nas concepções e práticas de avaliação das aprendizagens dos educadores de infância. A fase I centra-se na formulação de um referencial de competências transversais para a EPE inerentes à nova natureza dos saberes básicos do séc. XXI (Cachapuz, Sá-Chaves & Paixão, 2004) e no seu processo de transferibilidade e credibilidade através da reflexão/discussão do respectivo referencial com um painel de especialistas e profissionais. Identificaram-se quatro competências transversais a serem desenvolvidas pelas crianças centradas nas dimensões do aprender a aprender, aprender a comunicar e a expressar-se, aprender a ser e estar e aprender a reflectir. A fase II incide no diagnóstico das concepções de avaliação das aprendizagens na EPE e de colaboração Instituição/Família dos 6 educadores de infância, 17 pais e 17 crianças participantes no estudo, recorrendo a entrevistas, à análise documental e à observação de práticas. A análise dos dados recolhidos demonstra que é necessário recuperar um verdadeiro discurso didáctico e educativo da avaliação das aprendizagens, deixando de a conceber como sinónimo de medida e de objectividade e melhorando as práticas de avaliação de VII modo a potenciar o desenvolvimento de competências pelas crianças. A fase III preenche-se na construção e implementação de um programa de formação, creditado e correspondente a 50 horas, para educadores de infância sobre avaliação de competências na EPE em colaboração com a família. O programa de formação foi desenvolvido a partir (i) das concepções diagnosticadas, (ii) dos indicadores da investigação em formação contínua e em avaliação na EPE e (iii) de um modelo de desenvolvimento profissional baseado na reflexão, na observação e supervisão e na investigação-acção (Shön, 1992; Alarcão, 2000; Roldão, 2008; Cadório & Simão, 2011). Os indicadores obtidos demonstram que o programa de formação contribuiu para o enriquecimento profissional dos formandos ao nível da (re)construção de conhecimento, da reflexão constante e colaborativa sobre as práticas de avaliação, da mudança de atitudes e práticas de avaliação das aprendizagens e na compreensão mais profunda da complexidade, diversidade e necessidade de cada criança. Além disso, os indicadores obtidos também evidenciam a importância de uma avaliação das aprendizagens em colaboração com os pais das crianças para o desenvolvimento progressivo das competências transversais para a EPE e, consequentemente, para a obtenção de sucesso educativo. A fase IV consiste na avaliação do impacte do programa de formação nas concepções e práticas avaliativas dos educadores de infância através de, à semelhança da fase II, entrevistas aos 6 educadores de infância, aos 17 pais e às 17 crianças, à análise documental e à observação de práticas. Os resultados obtidos demonstram que o programa de formação teve impacte nas práticas de avaliação das aprendizagens a nível micro (decisões no interior da sala de actividades) e, mais reduzido, a nível meso (decisões a nível institucional). Os educadores de infância integraram nas suas práticas pedagógicas algumas estratégias avaliativas implementadas durante o programa de formação, consciencializando-se da importância da avaliação na EPE se centrar em procedimentos descritivos com enfoque na actividade da criança e na documentação e registo do trabalho realizado no dia-a-dia e do desenvolvimento de competências de cada criança (Gaustad, 1996; Parente, 2002). Contudo, e no que se refere à colaboração dos pais no processo de avaliação das aprendizagens das crianças, o programa de formação não proporcionou qualquer impacte nas práticas avaliativas dos educadores de infância. Apesar dos discursos transparecerem uma consciencialização da importância da família participar e influenciar a tomada de decisões ao longo do processo de avaliação das aprendizagens (Oliveira-Formosinho & Araújo, 2004), não foram tomadas medidas de mudança de práticas neste sentido, permanecendo os pais das crianças como sujeitos passivos neste processo. Uma visão integradora sobre os resultados obtidos ao longo da presente investigação revela a necessidade de se continuar a investigar e a construir novos caminhos na formação contínua dos educadores de infância de modo a recuperar um verdadeiro discurso educativo da avaliação das aprendizagens com impacte nas práticas pedagógicas e onde a família das crianças surja como parceira num trabalho a desenvolver colaborativamente.