969 research outputs found

    The social security rights of older international migrants in the European Union

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    Europe is now home to a significant and diverse population of older international migrants. Social and demographic changes have forced the issue of social security in old age onto the European social policy agenda in the last decade. In spite of an increased interest in the financial well-being of older people, many retired international migrants who are legally resident in the European Union face structured disadvantages. Four linked factors are of particular importance in shaping the pension rights and levels of financial provision available to individual older migrants: migration history, socio-legal status, past relationship to the paid labour market, and location within a particular EU Member State. Building on a typology of older migrants, the paper outlines the ways in which policy at both the European Union and Member State levels serves to diminish rather than enhance the social security rights of certain older international migrants

    Bioinformatic analysis of Entamoeba histolytica SINE1 elements

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    BACKGROUND: Invasive amoebiasis, caused by infection with the human parasite Entamoeba histolytica remains a major cause of morbidity and mortality in some less-developed countries. Genetically E. histolytica exhibits a number of unusual features including having approximately 20% of its genome comprised of repetitive elements. These include a number of families of SINEs - non-autonomous elements which can, however, move with the help of partner LINEs. In many eukaryotes SINE mobility has had a profound effect on gene expression; in this study we concentrated on one such element - EhSINE1, looking in particular for evidence of recent transposition. RESULTS: EhSINE1s were detected in the newly reassembled E. histolytica genome by searching with a Hidden Markov Model developed to encapsulate the key features of this element; 393 were detected. Examination of their sequences revealed that some had an internal structure showing one to four 26-27 nt repeats. Members of the different classes differ in a number of ways and in particular those with two internal repeats show the properties expected of fairly recently transposed SINEs - they are the most homogeneous in length and sequence, they have the longest (i.e. the least decayed) target site duplications and are the most likely to show evidence (in a cDNA library) of active transcription. Furthermore we were able to identify 15 EhSINE1s (6 pairs and one triplet) which appeared to be identical or very nearly so but inserted into different sites in the genome; these provide good evidence that if mobility has now ceased it has only done so very recently. CONCLUSIONS: Of the many families of repetitive elements present in the genome of E. histolytica we have examined in detail just one - EhSINE1. We have shown that there is evidence for waves of transposition at different points in the past and no evidence that mobility has entirely ceased. There are many aspects of the biology of this parasite which are not understood, in particular why it is pathogenic while the closely related species E. dispar is not, the great genetic diversity found amongst patient isolates and the fact, which may be related, that only a small proportion of those infected develop clinical invasive amoebiasis. Mobile genetic elements, with their ability to alter gene expression may well be important in unravelling these puzzles

    A simplified, Langendorff-free method for concomitant isolation of viable cardiac myocytes and non-myocytes from the adult mouse heart

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    Rationale: Cardiovascular disease represents a global pandemic. The advent of and recent advances in mouse genomics, epigenomics, and transgenics offer ever-greater potential for powerful avenues of research. However, progress is often constrained by unique complexities associated with the isolation of viable myocytes from the adult mouse heart. Current protocols rely on retrograde aortic perfusion using specialized Langendorff apparatus, which poses considerable logistical and technical barriers to researchers and demands extensive training investment. Objective: To identify and optimize a convenient, alternative approach, allowing the robust isolation and culture of adult mouse cardiac myocytes using only common surgical and laboratory equipment. Methods and Results: Cardiac myocytes were isolated with yields comparable to those in published Langendorff-based methods, using direct needle perfusion of the LV ex vivo and without requirement for heparin injection. Isolated myocytes can be cultured antibiotic free, with retained organized contractile and mitochondrial morphology, transcriptional signatures, calcium handling, responses to hypoxia, neurohormonal stimulation, and electric pacing, and are amenable to patch clamp and adenoviral gene transfer techniques. Furthermore, the methodology permits concurrent isolation, separation, and coculture of myocyte and nonmyocyte cardiac populations. Conclusions: We present a novel, simplified method, demonstrating concomitant isolation of viable cardiac myocytes and nonmyocytes from the same adult mouse heart. We anticipate that this new approach will expand and accelerate innovative research in the field of cardiac biology. </jats:sec

    Work restructuring and changing craft identity: the Tale of the Disaffected Weavers (or what happens when the rug is pulled from under your feet)

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    This article explores the changes in worker identity that can occur during manufacturing restructuring – specifically those linked to the declining status of craft work – through an in-depth case study of Weaveco, a UK carpet manufacturer. An analysis of changes in the labour process is followed by employee reactions centred on the demise of the traditional craft identity of male carpet weavers. The voices of the weavers dramatize the tensions involved in reconstructing their masculine identity, and we consider the implications this has for understanding gendered work relations

    Myocardin regulates vascular smooth muscle cell inflammatory activation and disease.

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    OBJECTIVE: Atherosclerosis, the cause of 50% of deaths in westernized societies, is widely regarded as a chronic vascular inflammatory disease. Vascular smooth muscle cell (VSMC) inflammatory activation in response to local proinflammatory stimuli contributes to disease progression and is a pervasive feature in developing atherosclerotic plaques. Therefore, it is of considerable therapeutic importance to identify mechanisms that regulate the VSMC inflammatory response. APPROACH AND RESULTS: We report that myocardin, a powerful myogenic transcriptional coactivator, negatively regulates VSMC inflammatory activation and vascular disease. Myocardin levels are reduced during atherosclerosis, in association with phenotypic switching of smooth muscle cells. Myocardin deficiency accelerates atherogenesis in hypercholesterolemic apolipoprotein E(-/-) mice. Conversely, increased myocardin expression potently abrogates the induction of an array of inflammatory cytokines, chemokines, and adhesion molecules in VSMCs. Expression of myocardin in VSMCs reduces lipid uptake, macrophage interaction, chemotaxis, and macrophage-endothelial tethering in vitro, and attenuates monocyte accumulation within developing lesions in vivo. These results demonstrate that endogenous levels of myocardin are a critical regulator of vessel inflammation. CONCLUSIONS: We propose myocardin as a guardian of the contractile, noninflammatory VSMC phenotype, with loss of myocardin representing a critical permissive step in the process of phenotypic transition and inflammatory activation, at the onset of vascular disease.This work was supported by Wellcome Trust funding for MAJ (Studentship 086799/Z/08/Z), British Heart Foundation grants (PG/10/007/28184) for AT, and (RG/08/009/25841) for MRB, and SS (FS/13/29/30024), the Cambridge NIHR Biomedical Research Centre and the NIH for JM (NIH HL-117907).This is the accepted manuscript of a paper published in Arteriosclerosis, Thrombosis, and Vascular Biology, 2015, doi: 10.1161/ATVBAHA.114.30521

    Echoes of time. The mobility of Brazilian researchers and students in Portugal

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    A investigação que apresentamos, de caráter exploratório, recaiu sobre histórias biográficas de brasileiros que escolhem Portugal para prosseguir formação e ou investigação. Procura-se encontrar na sua experiência elos de ligação explicativos sobre as motivações e os processos que os trazem para Portugal, assim como as expetativas e os projetos que comportam para os seus futuros e que incluem, ou não, este país. Temos em conta, especialmente, a forma como essa narrativa transporta sentidos identitários decorrentes das formas de relacionamento intercultural e político entre Portugal e Brasil e formas de cooperação implícitas, assim como mapas representacionais acerca dos lugares de eleição para desenvolvimento de carreiras científicas e académicas. A nossa pesquisa incide sobre as informações recolhidas através de um inquérito por questionário e entrevistas realizadas junto de estudantes e bolseiros brasileiros em Portugal.We present an exploratory study that investigated biographical stories of Brazilians who choose to continue their education or develop research in Portugal. We sought to find in their experiences explanatory links connecting the motivations and processes that bring them to Portugal, as well as the expectations and projects that they hold for the future, which may include, or not, this country. We take into account, particularly, the way this narrative carries senses of identity arising from the forms of intercultural and political relationship between Portugal and Brazil, as well as implicit forms of cooperation and representations about the places chosen for the development of scientific and academic careers. Our research draws on information collected through a survey based on questionnaires and interviews with Brazilian students and scholarship holders in Portugal.(undefined

    A consideration of the challenges involved in supervising international masters students

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    This paper explores the challenges facing supervisors of international postgraduate students at the dissertation stage of the masters programme. The central problems of time pressure, language difficulties, a lack of critical analysis and a prevalence of personal problems among international students are discussed. This paper makes recommendations for the improvement of language and critical thinking skills, and questions the future policy of language requirements at HE for international Masters students

    Genetic noise control via protein oligomerization

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    Gene expression in a cell entails random reaction events occurring over disparate time scales. Thus, molecular noise that often results in phenotypic and population-dynamic consequences sets a fundamental limit to biochemical signaling. While there have been numerous studies correlating the architecture of cellular reaction networks with noise tolerance, only a limited effort has been made to understand the dynamic role of protein-protein interactions. Here we have developed a fully stochastic model for the positive feedback control of a single gene, as well as a pair of genes (toggle switch), integrating quantitative results from previous in vivo and in vitro studies. We find that the overall noise-level is reduced and the frequency content of the noise is dramatically shifted to the physiologically irrelevant high-frequency regime in the presence of protein dimerization. This is independent of the choice of monomer or dimer as transcription factor and persists throughout the multiple model topologies considered. For the toggle switch, we additionally find that the presence of a protein dimer, either homodimer or heterodimer, may significantly reduce its random switching rate. Hence, the dimer promotes the robust function of bistable switches by preventing the uninduced (induced) state from randomly being induced (uninduced). The specific binding between regulatory proteins provides a buffer that may prevent the propagation of fluctuations in genetic activity. The capacity of the buffer is a non-monotonic function of association-dissociation rates. Since the protein oligomerization per se does not require extra protein components to be expressed, it provides a basis for the rapid control of intrinsic or extrinsic noise

    The study of HIV and antenatal care integration in pregnancy in Kenya: design, methods, and baseline results of a cluster-randomized controlled trial

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    Background: Despite strong evidence for the effectiveness of anti-retroviral therapy for improving the health of women living with HIV and for the prevention of mother-to-child transmission (PMTCT), HIV persists as a major maternal and child health problem in sub-Saharan Africa. In most settings antenatal care (ANC) services and HIV treatment services are offered in separate clinics. Integrating these services may result in better uptake of services, reduction of the time to treatment initiation, better adherence, and reduction of stigma. Methodology/Principal Findings: A prospective cluster randomized controlled trial design was used to evaluate the effects of integrating HIV treatment into ANC clinics at government health facilities in rural Kenya. Twelve facilities were randomized to provide either fully integrated services (ANC, PMTCT, and HIV treatment services all delivered in the ANC clinic) or non-integrated services (ANC clinics provided ANC and basic PMTCT services and referred clients to a separate HIV clinic for HIV treatment). During June 2009– March 2011, 1,172 HIV-positive pregnant women were enrolled in the study. The main study outcomes are rates of maternal enrollment in HIV care and treatment, infant HIV testing uptake, and HIVfree infant survival. Baseline results revealed that the intervention and control cohorts were similar with respect to sociodemographics, male partner HIV testing, sero-discordance of the couple, obstetric history, baseline CD4 count, and WHO Stage. Challenges faced while conducting this trial at low-resource rural health facilities included frequent staff turnover, stock-outs of essential supplies, transportation challenges, and changes in national guidelines. Conclusions/Significance: This is the first randomized trial of ANC and HIV service integration to be conducted in rural Africa. It is expected that the study will provide critical evidence regarding the implementation and effectiveness of this service delivery strategy, with important implications for programs striving to eliminate vertical transmission of HIV and improve maternal health
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