Cholesterol 24S-Hydroxylase overexpression inhibits the liver X receptor (LXR) pathway by activating small guanosine triphosphate-binding proteins (sGTPases) in neuronal cells

The neuronal-specific cholesterol 24S-hydroxylase (CYP46A1) is important for brain cholesterol elimination. Cyp46a1 null mice exhibit severe deficiencies in learning and hippocampal long-term potentiation, suggested to be caused by a decrease in isoprenoid intermediates of the mevalonate pathway. Conversely, transgenic mice overexpressing CYP46A1 show an improved cognitive function. These results raised the question of whether CYP46A1 expression can modulate the activity of proteins that are crucial for neuronal function, namely of isoprenylated small guanosine triphosphate-binding proteins (sGTPases). Our results show that CYP46A1 overexpression in SH-SY5Y neuroblastoma cells and in primary cultures of rat cortical neurons leads to an increase in 3-hydroxy-3-methyl-glutaryl-CoA reductase activity and to an overall increase in membrane levels of RhoA, Rac1, Cdc42 and Rab8. This increase is accompanied by a specific increase in RhoA activation. Interestingly, treatment with lovastatin or a geranylgeranyltransferase-I inhibitor abolished the CYP46A1 effect. The CYP46A1-mediated increase in sGTPases membrane abundance was confirmed in vivo, in membrane fractions obtained from transgenic mice overexpressing this enzyme. Moreover, CYP46A1 overexpression leads to a decrease in the liver X receptor (LXR) transcriptional activity and in the mRNA levels of ATP-binding cassette transporter 1, sub-family A, member 1 and apolipoprotein E. This effect was abolished by inhibition of prenylation or by co-transfection of a RhoA dominant-negative mutant. Our results suggest a novel regulatory axis in neurons; under conditions of membrane cholesterol reduction by increased CYP46A1 expression, neurons increase isoprenoid synthesis and sGTPase prenylation. This leads to a reduction in LXR activity, and consequently to a decrease in the expression of LXR target genes.

Preparação para a performance instrumental: problemáticas e estratégias: relatório de estágio

Resumo I (Prática Pedagógica) - Nesta seção do relatório de estágio pretende-se caraterizar e apresentar todos os elementos referentes à prática pedagógica, que fizeram parte do estágio do ensino especializado da música, realizado na Escola de Música do Orfeão de Leiria no ano letivo de 2013/2014. De uma forma geral, o relatório de estágio pretende colocar em evidência aspetos pedagógicos como metodologias de ensino, questões motivacionais, estilos de aprendizagem, entre outros. Durante um ano letivo completo foram analisados, com especial atenção, três alunos que foram envolvidos no estágio, construindo e modelando os seus processos de aprendizagem. Para cada um deles foi realizado, ao longo do ano letivo, 30 planos de aula, uma planificação anual e três gravações vídeo/áudio em contexto de aula. Não foi uma tarefa nada fácil de realizar, mas que trouxe inúmeros conhecimentos não só de caráter pedagógico mas também de caráter pessoal. A parte inicial desta seção será dedicada à descrição e caraterização da escola onde foi realizado o estágio, a Escola de Música do Orfeão de Leiria/Conservatório de Artes. Será feita uma pequena abordagem histórica da instituição, bem como do seu projeto educativo, dacomunidade escolar, do seu contexto sociocultural e da classe de saxofone. Será apresentada também uma caraterização dos alunos, segundo vários parâmetros. Posteriormente, serão descritas algumas das práticas educativas desenvolvidas, com os alunos, em contexto de estágio. Para tal, serão utilizados como instrumentos, não só a experiência ativa do docente/estagiário, mas também todas as gravações, planos de aulas e planificações anuais, realizados em contexto de estágio do ensino especializado. Por fim, será realizada uma reflexão crítica do desempenho como docente de saxofone no âmbito do estágio e uma conclusão de toda a seção da prática pedagógica.

Domesticating portuguese television

This chapter discusses the role of television within Portuguese family life. In particular, it examines how the domestication of television within the home is influenced by the social context in which different types of families live. The research is framed around the theory of domestication and based on 50 semi-structured interviews.1 “Domestication” is the process by which the household and its surroundings (both private and the public), together with the moral and formal or objective economy, are related to each other and become mutually constitutive (Silverstone, Hirsch and Morley 1999). The metaphor of “domestication” originally comes from the taming of wild animals, but has been usefully applied to the “domestication” of information communication technology (ICT), including television, within the home. Silverstone et al. (1999) have developed a range of concepts to capture this process, of which the best known are: “appropriation”, “objectification”, “incorporation” and “conversion”. These categories describe how the entry of ICT into the home is managed; how artefacts are physically (and symbolically) placed within the home; how they are adapted into everyday routines; and how they are displayed to others (Haddon 2007, 26). These four key concepts will be used in this chapter to discuss the importance of television within Portugal as an example of a small country in which there has been little research using this particular theoretical approach. Most studies on Portuguese television have focused on televisual history or come from research into trends in television consumption. The domestication theory is a holistic framework, useful to explain the meaning of television in Portuguese homes in all the stages of its presence in daily life. This forms part of a larger international project entitled Digital Inclusion and Participation: Comparing the Trajectories of Digital Media Use by Majority and Disadvantage Groups in Portugal and in the USA (UT Austin/Portugal Program).

Diagnóstico de avarias em máquinas rotativas utilizando a análise de órbitas

Trabalho Final de Mestrado para obtenção do grau de Mestre em Engenharia Mecânica Perfil Manutenção e Produção

Carcinoma neuroendócrino de pequenas células: um estudo de caso em citopatologia ginecológica

O presente estudo reporta o caso de uma mulher de 63 anos da qual a única informação clínica era a suspeita de um sarcoma da cérvix. Simultaneamente à colpocitologia, foram enviadas biópsias do colo e do endométrio para diagnóstico. A visualização da amostra citológica revelou vários agregados de número variável de células monótonas, com tamanho pequeno, formato redondo e citoplasma escasso, num fundo com diátese. Os núcleos apresentavam moldagem, hipercromasia, cromatina “sal-e-pimenta” e ausência de nucléolos. O aspeto microscópico das biópsias foi concordante com os achados citológicos, tendo sido igualmente identificados focos glanduliformes com características atípicas. A neoplasia mostrou expressão imunohistoquímica dos antigénios enolase neurónio-específica (neuron specific enolase, NSE), sinaptofisina e citoqueratina (clones AE1/AE3), e uma elevada atividade proliferativa demonstrada pela imunorreactividade para o marcador nuclear Ki67/Mib1. Os achados citológicos, histológicos e imunohistoquímicos foram consistentes com o diagnóstico de carcinoma neuroendócrino de pequenas células. Dos tumores cervicais, esta neoplasia maligna é das mais raras, mostrando um comportamento muito agressivo, com prognóstico muito pobre, em que as terapêuticas existentes são pouco consensuais quanto à sua eficácia. A sua etiologia ainda é estudada, podendo estar relacionada com a infeção pelo Vírus do Papiloma Humano.

Genotoxic assessment in different exposure groups working with antineoplastic agents

Antioneoplastic drugs are widely used in treatment of cancer, and several studies suggest acute and long-term effects associated to antineoplastic drug exposures, namely associating workplace exposure with health effects. Cytokinesis blocked micronucleus (CBMN) assay is one promising short-term genotoxicity assays for human risk assessment and their combination is recommended to monitor populations chronically exposed to genotoxic agents. The aim of this investigation is the genotoxicity assessment in different professionals that handle cytostatics drugs. This research is case-control blinded study constituted by 46 non-exposed subjects and 44 workers that handle antineoplastic drugs, such as pharmacists, pharmacy technicians, and nurses. It was found statistically significant increases in the genotoxicity biomarkers in exposed comparising with controls (p<0.05). The findings address the need for regular biomonitoring of personnel occupationally exposed to these drugs, confirming to an enhanced health risk assessment.

Invariant integrals applied to nematic liquid crystals with small Ericksen number and topological defects

Invariant integrals are derived for nematic liquid crystals and applied to materials with small Ericksen number and topological defects. The nematic material is confined between two infinite plates located at y = -h and y = h (h is an element of R+) with a semi-infinite plate at y = 0 and x < 0. Planar and homeotropic strong anchoring boundary conditions to the director field are assumed at these two infinite and semi-infinite plates, respectively. Thus, a line disclination appears in the system which coincides with the z-axis. Analytical solutions to the director field in the neighbourhood of the singularity are obtained. However, these solutions depend on an arbitrary parameter. The nematic elastic force is thus evaluated from an invariant integral of the energy-momentum tensor around a closed surface which does not contain the singularity. This allows one to determine this parameter which is a function of the nematic cell thickness and the strength of the disclination. Analytical solutions are also deduced for the director field in the whole region using the conformal mapping method. (C) 2013 Elsevier Ltd. All rights reserved.

Reactivity of bulky tris(Phenylpyrazolyl) methanesulfonate copper(I) complexes towards small unsaturated molecules

Reaction of the tris(3-phenylpyrazolyl)methane sulfonate species (Tpms(Ph))Li with the copper(I) complex [Cu(MeCN)(4)][PF6] affords [Cu(Tpms(Ph))(MeCN)] 1. The latter, upon reaction with equimolar amounts of cyclohexyl-(CyNC) or 2,6-dimethylphenyl (XylNC) isocyanides, or excess CO, furnishes the corresponding Cu(I)complexes [Cu(Tpms(Ph))(CNR)] (R = Cy 2, Xyl 3) or [Cu(Tpms(Ph))(CO)] 4. The ligated isocyanide in 2 or 3 (or the acetonitrile ligand in 1)is displaced by 3-iminoisoindolin-1-one to afford 5, the first copper(I) complex containing an 3-iminoisoindolin-1-one ligand. The ligated acetonitrile in 1 undergoes nucleophilic attack by methylamine to give the amidine complex [Cu(Tpms(Ph)){MeC(NH)NHMe}] 6, whereas only the starting materials were recovered from the attempted corresponding reactions of 2 and 3 with methylamine. Complexes 1 or 6 form the trinuclear hydroxo-copper(II)species [(mu-Cu){Cu(mu-OH) (2)(Tpms(Ph))}(2)] 7 upon air oxidation in moist methanol. In all the complexes the scorpionate ligand facially caps the metal in the N,N,O-coordination mode.

Síntese de um novo polímero conjugado e reticulável e sua aplicação em células fotovoltaicas

Trabalho Final de Mestrado para obtenção do Grau de Mestre em Engenharia Química e Biológica

Otimização energética em redes óticas de próxima geração Flex-grid vs Fixed-grid

Trabalho Final de Mestrado para obtenção do grau de Mestre em Engenharia de Eletrónica e Telecomunicações

Comunidade real, comunidade imaginada: observação participante em contexto de estágio numa associação cultural: relatório de estágio

Relatório de Estágio submetido à Escola Superior de Teatro e Cinema para cumprimento dos requisitos necessários à obtenção do grau de Mestre em Teatro - especialização em Teatro e Comunidade.

Recurring contact opportunities within groups of devices

The capability to anticipate a contact with another device can greatly improve the performance and user satisfaction not only of mobile social network applications but of any other relying on some form of data harvesting or hoarding. One of the most promising approaches for contact prediction is to extrapolate from past experiences. This paper investigates the recurring contact patterns observed between groups of devices using an 8-year dataset of wireless access logs produced by more than 70000 devices. This effort permitted to model the probabilities of occurrence of a contact at a predefined date between groups of devices using a power law distribution that varies according to neighbourhood size and recurrence period. In the general case, the model can be used by applications that need to disseminate large datasets by groups of devices. As an example, the paper presents and evaluates an algorithm that provides daily contact predictions, based on the history of past pairwise contacts and their duration. Copyright © 2015 ICST.