Effects of rosiglitazone and linoleic acid on human preadipocyte differentiation

Background Peroxisome proliferator activated receptor gamma (PPARgamma) is a ligand-activated transcription factor known to be central to both adipose tissue development and insulin action. Growth of adipose tissue requires differentiation of preadipocytes with acquisition of specific cellular functions including insulin sensitivity, leptin secretion and the capacity to store triglyceride. Dietary fatty acids and members of the thiazolidinedione class of compounds have been reported to influence adipogenesis at the transcriptional level. Here, we compare the effects of a dietary fatty acid, linoleic acid, and a thiazolidinedione, rosiglitazone, on biochemical and functional aspects of human preadipocyte differentiation in vitro . Materials and methods Human omental and subcutaneous preadipocytes were subcultured 2-3 times and subsequently differentiated for 21 days in the presence of either linoleic acid or rosiglitazone. Differentiation was assessed using a number of biochemical and functional parameters. Results Omental and subcutaneous preadipocytes differentiated in the presence of linoleic acid showed marked cytoplasmic triacylglycerol accumulation however, no biochemical markers of differentiation (LPL expression, G3PDH gene expression and enzyme activity and leptin expression or secretion) were detected. In contrast, treatment of these cells with rosiglitazone induced full biochemical differentiation as judged by all markers assessed, despite comparatively little lipid accumulation. The rosiglitazone effects were subcutaneous depot-specific. Cells treated with linoleic acid showed decreased glucose uptake cf rosiglitazone-treated cells. A luciferase reporter assay demonstrated that rosiglitazone potently activates h-peroxisome proliferator activated receptor gamma while linoleic acid had no effect. Conclusions These studies demonstrate that (a) human preadipocytes have the potential to accumulate triacylglycerol irrespective of their stage of biochemical differentiation; (b) while omental preadipocytes are refractory to biochemical differentiation in vitro , they are able to accumulate triacylglycerol; and (c) rosiglitazone and linoleic acid may exert their effects via different biochemical pathways.

Greater replication and differentiation of preadipocytes in inherited corticosteroid-binding globulin deficiency

Glucocorticoids are pivotal for adipose tissue development. Rodent studies suggest that corticosteroid-binding globulin (CBG) modulates glucocorticoid action in adipose tissue. In humans, both genetic CBG deficiency and suppressed CBG concentrations in hyperinsulinemic states are associated with obesity. We hypothesized that CBG deficiency in humans modulates the response of human preadipocytes to glucocorticoids, predisposing them to obesity. We compared normal preadipocytes with subcultured preadipocytes from an individual with the first ever described complete deficiency of CBG due to a homozygous null mutation. CBG-negative preadipocytes proliferated more rapidly and showed greater peroxisome proliferator-activated receptor-gamma-mediated differentiation than normal preadipocytes. CBG was not expressed in normal human preadipocytes. Glucocorticoid receptor number and binding characteristics and 11beta-hydroxysteroid dehydrogenase activity were similar for CBG-negative and normal preadipocytes. We propose that the increased proliferation and enhanced differentiation of CBG-negative preadipocytes may promote adipose tissue deposition and explain the obesity seen in individuals with genetic CBG deficiency. Furthermore, these observations may be relevant to obesity occurring with suppressed CBG concentrations associated with hyperinsulinemia.

Role of HuR in skeletal myogenesis through coordinate regulation of muscle differentiation genes

In this report, we investigate the role of the RNA-binding protein HuR during skeletal myogenesis. At the onset of myogenesis in differentiating C2C12 myocytes and in vivo in regenerating mouse muscle, HuR cytoplasmic abundance increased dramatically, returning to a predominantly nuclear presence upon completion of myogenesis. mRNAs encoding key regulators of myogenesis-specific transcription (myogenin and MyoD) and cell cycle withdrawal (p21), bearing AU-rich regions, were found to be targets of HuR in a differentiation-dependent manner. Accordingly, mRNA half-lives were highest during differentiation, declining when differentiation was completed. Importantly, HuR-overexpressing C2C12 cells displayed increased target mRNA expression and half-life and underwent precocious differentiation. Our findings underscore a critical function for HuR during skeletal myogenesis linked to HuR's coordinate regulation of muscle differentiation genes.

Garantia de qualidade de serviço (QOS) em arquitecturas MPLS

Os prestadores de serviços de telecomunicações e operadores de telecomunicações deparam-se com um aumento exponencial das necessidades de largura de banda. A evolução e massificação dos serviços Internet e Intranet pelos serviços públicos e privados deixaram de ser uma mera adaptação do protocolo TCP, à qualidade da ligação sendo uma necessidade a diferenciação do tráfego. As metodologias que asseguram uma qualidade de serviço no âmbito dos fornecedores de serviços internet são a forma de garantir uma qualidade de serviço adequada a cada tipo de tráfego. Estas metodologias são suportadas pela rede IP MPLS dos diversos operadores de telecomunicações no transporte dos diversos serviços dos seus clientes empresarias e domésticos no acesso à internet dos diversos serviços públicos de dados e voz e nas redes virtuais privadas. Os portais aplicacionais são a interface directa com o cliente para definição dos acordos de nível de serviço “Service Level Agreements” e a sua associação à especificação dos níveis de serviço “Service Level Specification”, para posterior relação com a definição de métricas adequadas à qualidade de serviço acordada com o cliente no desenho dos serviços de uma rede IP “MultiProtocol Label Switch”. A proposta consiste em criar uma metodologia para mapear as necessidades de serviços dos clientes em SLAs e registá-los numa base de dados, separando claramente a qualidade do serviço vista na óptica do operador em: arquitectura de rede de transporte, arquitectura do serviço e arquitectura de monitoria. Estes dados são mapeados em parâmetros e especificações de implementação dos serviços de suporte ao negócio do operador tendo em vista a criação de um “Work Flow” fim a fim. Paralelamente define-se os serviços a disponibilizar comercialmente, o conjunto de serviços suportados pela rede e tecnologia IP MPLS com a parametrização de ”Quality of Service Assurance” adequada a cada um, cria-se uma arquitectura de rede de suporte ao transporte base entre os diversos equipamentos agregadores de acessos através do “Backbone”, define-se uma arquitectura de suporte para cada tipo de serviço independente da arquitectura de transporte. Neste trabalho implementam-se algumas arquitecturas de QoS estudadas no IP MPLS em simuladores disponibilizados pela comunidade “Open Source” e analisamos as vantagens de desvantagens de cada uma. Todas as necessidades são devidamente equacionadas, prevendo o seu crescimento, desempenho, estabelecendo regras de distribuição de largura de banda e análise de desempenho, criando redes escaláveis e com estimativas de crescimento optimistas. Os serviços são desenhados de forma a adaptarem-se à evolução das necessidades aplicacionais, ao crescimento do número de utilizadores e evolução do próprio serviço.

Habitat differentiation between groups of Risso's dolphins as evidence of coastal nursery areas

26th Annual Conference of the European Cetacean Society, Galway, Ireland 26-28 March 2012.

QoS em WIMAX – Análise e avaliação de módulos para simulação com o ns-2

Mestrado em Engenharia Electrotécnica e de Computadores

Effects of antihypertensive drugs in the differentiation and activation of human bone cells

O osso é um tecido metabolicamente ativo e a sua remodelação é importante para regular e manter a massa óssea. Esse processo envolve a reabsorção do material ósseo por ação dos osteoclastos e a síntese de novo material ósseo mediado pelos osteoblastos. Vários estudos têm sugerido que a pressão arterial elevada está associada a alterações no metabolismo do cálcio, o que leva ao aumento da perda de cálcio e da remoção de cálcio do osso. Embora as alterações no metabolismo ósseo sejam um efeito adverso associado a alguns fármacos antihipertensores, o conhecimento em relação a este efeito terapêutico ligado com os bloqueadores de canais de cálcio é ainda muito escasso. Uma vez que os possíveis efeitos no osso podem ser atribuídos à ação antihipertensiva dessas moléculas, ou através de um efeito direto nas atividades metabólicas ósseas, torna-se necessário esclarecer este assunto. Devido ao facto de que as alterações no metabolismo ósseo são um efeito adverso associado a alguns fármacos antihipertensores, o objetivo deste trabalho é avaliar o efeito que os bloqueadores dos canais de cálcio exercem sobre as células ósseas humanas, nomeadamente osteoclastos, osteoblastos e co-culturas de ambos os tipos celulares. Verificou-se que os efeitos dos fármacos antihipertensores variaram consoante o fármaco testado e o sistema de cultura usado. Alguns fármacos revelaram a capacidade de estimular a osteoclastogénese e a osteoblastogénese em concentrações baixas. Independentemente da identidade do fármaco, concentrações elevadas revelaram ser prejudiciais para a resposta das células ósseas. Os mecanismos intracelulares através dos quais os efeitos foram exercidos foram igualmente afetados de forma diferencial pelos diferentes fármacos. Em resumo, este trabalho demonstrou que os bloqueadores dos canais de cálcio utilizados possuem a capacidade de afetar direta- e indiretamente a resposta de células ósseas humanas, cultivadas isoladamente ou co-cultivadas. Este tipo de informação é crucial para compreender e prevenir os potenciais efeitos destes fármacos no tecido ósseo, e também para adequar e eventualmente melhorar a terapêutica antihipertensora de cada paciente.

Students' engagement in schools : differentiation and promotion

The objective of this work is to present elements of the project Student engagement in Schools (SES). The team consists of 10 researchers from six Universities. Student engagement in schools is a multidimensional construct that unites affective, behavioural, and cognitive dimensions of student adaptation in the school and has influence on students’outcomes. The team of researchers conceptualized two major studies, a differential study to analyze the relations between SES and contextual factors, personal factors, student’s outcomes, and a quasi-experimental study to analyze the effects on SES of a specific intervention programmes. In study 1, the sample size is around 600 students (150 6th graders, 150 7th graders, 150 9th graders, and 150 10th graders). We shall focus on years of school transition, with rural and urban populations, on different regions of the country, and on students with different family background. We shall conduct questionnaires with national and international scales. The study 2 will involve students in 7th and 9th grade, from four classes, two of the experimental group and two of the control group. Patterns of verbal communication between a teacher and students can influence the classroom environment and SES. This model of communication would result in more effective student management and more time on-task for learning.

Code offloading on real-time multimedia systems: a framework for handling code mobility and code offloading in a QoS aware environment

Actualmente, os smartphones e outros dispositivos móveis têm vindo a ser dotados com cada vez maior poder computacional, sendo capazes de executar um vasto conjunto de aplicações desde simples programas de para tirar notas até sofisticados programas de navegação. Porém, mesmo com a evolução do seu hardware, os actuais dispositivos móveis ainda não possuem as mesmas capacidades que os computadores de mesa ou portáteis. Uma possível solução para este problema é distribuir a aplicação, executando partes dela no dispositivo local e o resto em outros dispositivos ligados à rede. Adicionalmente, alguns tipos de aplicações como aplicações multimédia, jogos electrónicos ou aplicações de ambiente imersivos possuem requisitos em termos de Qualidade de Serviço, particularmente de tempo real. Ao longo desta tese é proposto um sistema de execução de código remota para sistemas distribuídos com restrições de tempo-real. A arquitectura proposta adapta-se a sistemas que necessitem de executar periodicamente e em paralelo mesmo conjunto de funções com garantias de tempo real, mesmo desconhecendo os tempos de execução das referidas funções. A plataforma proposta foi desenvolvida para sistemas móveis capazes de executar o Sistema Operativo Android.

Epigenetic and transcriptional signatures of stable versus plastic differentiation of proinflammatory gd T cell subsets

Two distinct subsets of γδ T cells that produce interleukin 17 (IL-17) (CD27(-) γδ T cells) or interferon-γ (IFN-γ) (CD27(+) γδ T cells) develop in the mouse thymus, but the molecular determinants of their functional potential in the periphery remain unknown. Here we conducted a genome-wide characterization of the methylation patterns of histone H3, along with analysis of mRNA encoding transcription factors, to identify the regulatory networks of peripheral IFN-γ-producing or IL-17-producing γδ T cell subsets in vivo. We found that CD27(+) γδ T cells were committed to the expression of Ifng but not Il17, whereas CD27(-) γδ T cells displayed permissive chromatin configurations at loci encoding both cytokines and their regulatory transcription factors and differentiated into cells that produced both IL-17 and IFN-γ in a tumor microenvironment.

QoS-based surrogates selection and service proposal formulation in offloading environments

Resource constraints are becoming a problem as many of the wireless mobile devices have increased generality. Our work tries to address this growing demand on resources and performance, by proposing the dynamic selection of neighbor nodes for cooperative service execution. This selection is in uenced by user's quality of service requirements expressed in his request, tailoring provided service to user's speci c needs. In this paper we improve our proposal's formulation algorithm with the ability to trade o time for the quality of the solution. At any given time, a complete solution for service execution exists, and the quality of that solution is expected to improve overtime.

An Ada framework for QoS-Aware applications

In this paper we present a framework for managing QoS-aware applications in a dynamic, ad-hoc, distributed environment. This framework considers an available set of wireless/mobile and fixed nodes, which may temporally form groups in order to process a set of related services, and where there is the need to support different levels of service and different combinations of quality requirements. This framework is being developed both for testing and validating an approach, based on multidimensional QoS properties, which provides service negotiation and proposal evaluation algorithms, and for assessing the suitability of the Ada language to be used in the context of dynamic, QoS-aware systems.

Dynamic QoS-Aware coalition formation

Users of wireless devices increasingly demand access to multimedia content with speci c quality of service requirements. Users might tolerate di erent levels of service, or could be satis ed with di erent quality combinations choices. However, multimedia processing introduces heavy resource requirements on the client side. Our work tries to address the growing demand on resources and performance requirements, by allowing wireless nodes to cooperate with each other to meet resource allocation requests and handle stringent constraints, opportunistically taking advantage of the local ad-hoc network that is created spontaneously, as nodes move in range of each other, forming a temporary coalition for service execution. Coalition formation is necessary when a single node cannot execute a speci c service, but it may also be bene cial when groups perform more e ciently when compared to a single s node performance.

QoS of IP services in a fieldbus network: on the limitations and possible improvements

This paper focuses on the problem of providing efficient scheduling mechanisms for IP packets encapsulated in the frames of a real-time fieldbus network - the PROFIBUS. The approach described consists on a dual-stack approach encompassing both the controlrelated traffic ("native" fieldbus traffic) and the IPrelated traffic. The overall goal is to maintain the hard real-time guarantees of the control-related traffic, while at the same time providing the desired quality of service (QoS) to the coexistent IP applications. We start to describe the work which have been up to now carried out in the framework of the European project RFieldbus (High Performance Wireless Fieldbus in Industrial Multimedia-Related Environments - IST-1999-11316). Then we identify its limitations and point out solutions that are now being addressed out of the framework of the above-mentioned European project.

QoS-enabled middleware for smart grids

Emerging smart grid systems must be able to react quickly and predictably, adapting their operation to changing energy supply and demand, by controlling energy consuming and energy storage devices. An intrinsic problem with smart grids is that energy produced from in-house renewable sources is affected by fluctuating weather factors. The applications driving smart grids operation must rely on a solid communication network that is secure, highly scalable, and always available. Thus, any communication infrastructure for smart grids should support its potential of producing high quantities of real-time data, with the goal of reacting to state changes by actuating on devices in real-time, while providing Quality of Service (QoS).