998 resultados para Key, Emil, 1822-1892.
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Dissertação de mestrado em Engenharia Industrial
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Dissertação de mestrado em Design e Marketing
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Dissertação de mestrado integrado em Engenharia e Gestão Industrial
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Depression is an extremely heterogeneous disorder. Diverse molecular mechanisms have been suggested to underlie its etiology. To understand the molecular mechanisms responsible for this complex disorder, researchers have been using animal models extensively, namely mice from various genetic backgrounds and harboring distinct genetic modifications. The use of numerous mouse models has contributed to enrich our knowledge on depression. However, accumulating data also revealed that the intrinsic characteristics of each mouse strain might influence the experimental outcomes, which may justify some conflicting evidence reported in the literature. To further understand the impact of the genetic background, we performed a multimodal comparative study encompassing the most relevant parameters commonly addressed in depression, in three of the most widely used mouse strains: Balb/c, C57BL/6, and CD-1. Moreover, female mice were selected for this study taken into account the higher prevalence of depression in women and the fewer animal studies using this gender. Our results show that Balb/c mice have a more pronounced anxious-like behavior than CD-1 and C57BL/6 mice, whereas C57BL/6 animals present the strongest depressive-like trait. Furthermore, C57BL/6 mice display the highest rate of proliferating cells and brain-derived neurotrophic factor (Bdnf) expression levels in the hippocampus, while hippocampal dentate granular neurons of Balb/c mice show smaller dendritic lengths and fewer ramifications. Of notice, the expression levels of inducible nitric oxide synthase (iNos) predict 39.5% of the depressive-like behavior index, which suggests a key role of hippocampal iNOS in depression. Overall, this study reveals important interstrain differences in several behavioral dimensions and molecular and cellular parameters that should be considered when preparing and analyzing experiments addressing depression using mouse models. It further contributes to the literature by revealing the predictive value of hippocampal iNos expression levels in depressive-like behavior, irrespectively of the mouse strain.
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Granulomas are the hallmark of mycobacterial disease. Here, we demonstrate that both the cell recruitment and the increased glucose consumption in granulomatous infiltrates during Mycobacterium avium infection are highly dependent on interferon-y (IFN-y). Mycobacterium avium-infected mice lacking IFN-y signalling failed to developed significant inflammatory infiltrations and lacked the characteristic uptake of the glucose analogue fluorine-18-fluorodeoxyglucose (FDG). To assess the role of macrophages in glucose uptake we infected mice with a selective impairment of IFN-y signalling in the macrophage lineage (MIIG mice). Although only a partial reduction of the granulomatous areas was observed in infected MIIG mice, the insensitivity of macrophages to IFN-y reduced the accumulation of FDG. In vivo, ex vivo and in vitro assays showed that macrophage activated by IFN-y displayed increased rates of glucose uptake and in vitro studies showed also that they had increased lactate production and increased expression of key glycolytic enzymes. Overall, our results show that the activation of macrophages by IFN-y is responsible for the Warburg effect observed in organs infected with M. avium.
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Dissertação de mestrado em Engenharia Industrial
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The Optic atrophy 1 protein (OPA1) is a key element in the dynamics and morphology of mitochondria. We demonstrated that the absence of I?B kinase-a, which is a key element of the nonclassical NF-?B pathway, has an impact on the mitochondrial network morphology and OPA1 expression. In contrast, the absence of NF-?B essential modulator (NEMO) or I?B kinase-ß, both of which are essential for the canonical NF-?B pathway, has no impact on mitochondrial dynamics. Whereas Parkin has been reported to positively regulate the expression of OPA1 through NEMO, herein we found that PARK2 overexpression did not modify the expression of OPA1. PARK2 expression reduced the levels of Bax, and it prevented stress-induced cell death only in Bak-deficient mouse embryonic fibroblast cells. Collectively, our results point out a role of the nonclassical NF-?B pathway in the regulation of mitochondrial dynamics and OPA1 expression.
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Dissertação de mestrado em Engenharia Industrial
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Dissertação de mestrado em Systems Engineering
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Dissertação de mestrado em Engenharia Humana
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Dissertação de mestrado em Engenharia Humana
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A educação em saúde conheceu, no último século, profundas mudanças, tanto no plano conceitual como no das práticas dele decorrentes, fruto das transformações por que passou a humanidade em termos políticos, económicos e sociais. O conceito de educação desviou-se da perspectiva instruidora e escolarizadora de crianças e jovens, centrada na transmissão-assimilação de conhecimentos, para uma perspectiva mais abrangente e integradora, centrada na criação de condições que permitem aos indivíduos desenvolverem-se holisticamente na sua multidimensionalidade, em permanente interação com os outros. Por sua vez, o conceito de saúde perdeu o seu pendor negativo de ausência de doença, passando a ser entendido positivamente como um estado de completo bem-estar físico, mental, social e espiritual, em constante mutação ao longo da vida. Nesse sentido, a educação em saúde deixou também de ser vista como a transmissão de informação de caráter higienisto-sanitário, orientada para a prevenção ou o tratamento da doença, efetuada em contextos formais, para passar a ser entendida como a capacitação dos indivíduos para controlarem os seus próprios determinantes de saúde, através da criação ou do desenvolvimento de competências de ação. A educação e a saúde passam, pois, a apresentar-se como duas faces de um mesmo processo. Neste trabalho pretendemos, pois, analisar a evolução conceptual em torno da saúde e da educação no séc. XX, tentando perceber até que ponto essas mudanças conceptuais se têm refletido ao nível das práticas.
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[Extrat] The advent of thc internet raised questions about the role of radio in a fast-changing media environment. Many voices forecast its end but in the summer of 2008 the Swedish Radio and TV Authority published a study named 'The Future of Radio', which clearly opposed the pessimism of recent analysis. While the study anticipates the exhaustion of the FM model, it clearly broadens perspectives for DAB and internet radio, highlighting digitalization as the key element for the future relevance of radio. The Portuguese researcher and radio professional João Paulo Meneses states that 'the future of radio relies upon the internet', calling the broad service offerings of the net the pathway for the survival of radio from the threats to its two essential aspects: rnobility and accumulation (Meneses 2008). Accumulation is radio's capability to be used in a nonexclusive manner, which means that a listener can use the radio while performing other activities, like cooking, sewing, reading, writing or jogging.
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Dissertação de mestrado integrado em Engenharia e Gestão Industrial
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Tuberculosis presents a myriad of symptoms, progression routes and propagation patterns not yet fully understood. Whereas for a long time research has focused solely on the patient immunity and overall susceptibility, it is nowadays widely accepted that the genetic diversity of its causative agent, Mycobacterium tuberculosis, plays a key role in this dynamic. This study focuses on a particular family of genes, the mclxs (Mycobacterium cyclase/LuxR-like genes), which codify for a particular and nearly mycobacterial-exclusive combination of protein domains. mclxs genes were found to be pseudogenized by frameshift-causing insertion(s)/deletion(s) in a considerable number of M. tuberculosis complex strains and clinical isolates. To discern the functional implications of the pseudogenization, we have analysed the pattern of frameshift-causing mutations in a group of M. tuberculosis isolates while taking into account their microbial-, patient- and disease-related traits. Our logistic regression-based analyses have revealed disparate effects associated with the transcriptional inactivation of two mclx genes. In fact, mclx2 (Rv1358) pseudogenization appears to be primarily driven by the microbial phylogenetic background, being mainly related to the Euro-American (EAm) lineage; on the other hand, mclx3 (Rv2488c) presents a higher tendency for pseudogenization among isolates from patients born on the Western Pacific area, and from isolates causing extra-pulmonary infections. These results contribute to the overall knowledge on the biology of M. tuberculosis infection, whereas at the same time launch the necessary basis for the functional assessment of these so far overlooked genes.