29,755 research outputs found

    Chronic-moderate ethanol exposure of L(tk-) cells expressing ? 4? 3? GABAA receptors reduces potency of allopregnanolone potentiation of GABA-evoked inward currents: Possible role of PKC

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    Aim: To investigate the effect of chronic-moderate ethanol (CME) treatment upon direct activation and allosteric modulation of GABAA receptors, and to assess the sensitivity of these parameters to PKC inhibition in control and ethanol-treated cells. Methods: L(tk-) cells were exposed to 20mM ethanol in culture media for 14 days prior to induction of stable expression of human recombinant ?4?3? receptors using dexamethasone. Concentration-response curves for GABA (1nM - 100µM), and allopregnanolone (ALLO; 1nM - 30µM) co-applied with 200nM GABA were obtained using whole-cell patch-clamp electrophysiology at a holding voltage of -60 mV. 400nM calphostin C (CphC) or vehicle (DMSO) was administered to cells via the pipette solution, which was prepared with 2mM Mg.ATP. SDS-PAGE and western blotting were used to compare levels of whole-cell expression, quantified relative to ?-actin, of ?4 and ? GABAA receptor subunits, and several isoforms of PKC (?, ?, ?, and ?), in control and CME-treated cells. Data was reported as Mean ± SEM and significance determined by either one-way ANOVA with Newman-Keuls multiple comparison tests, or two-way, unpaired t-tests. Results: Expression of ?4 subunits was reduced 35% (P0.05) and pEC50 (control: 6.18±0.04, n=13, CME: 6.17±0.04, n=4, P>0.05) of GABA were unchanged. CphC increased the GABA pEC50 relative to control (6.62±0.08, n=3, P<0.001) but had no effect upon responses at pEC20 GABA. Following CME, the potency of GABA was unaltered in the presence of CphC. The magnitude of ALLO-induced potentiation in control cells (7.34±0.6 fold, n=19) was unchanged by CME (ATP: 7.39±1.0 fold, n=9, P>0.05), and CphC had no significant effect in control or CME-treated cells. The ALLO pEC50 in control cells (6.23±0.05, n=19) was unaffected by CphC. Following CME, the potency of ALLO was reduced (5.68±0.06, n=9, P<0.001) but was enhanced in the presence of CphC, which restored potency almost back to control levels (5.94±0.09, n=5, P<0.05 relative to control). Expression of the ?, ?, ?, and ? isoforms of PKC was detected in whole-cell lysates of L(tk-) cells but only PKC? was significantly altered by CME treatment, exhibiting a nearly 4-fold increase (3.9±0.47 fold P<0.01) when compared with that in controls. Discussion: CME of un-induced L(tk-) cells was sufficient to alter sensitivity of ?4?3? receptor function to alterations of the balance of phosphorylation induced by CphC. The increased expression of PKC? after CME may have been directly related to the absence of effect of CphC upon GABA potency. As direct interaction of GABAA receptors with PKC? has not been determined, the effects observed for potency and efficacy of ALLO following CME may be indicative of changes to the phosphorylation of accessory proteins or other PKC isoforms by PKC?

    'It burdens me': The impact of stroke in central Aceh, Indonesia

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    This is the accepted version of the following article: Norris, M., Allotey, P. and Barrett, G. (2012), ‘It burdens me’: the impact of stroke in central Aceh, Indonesia. Sociology of Health & Illness, 34: 826–840. doi: 10.1111/j.1467-9566.2011.01431.x, which has been published in final form at http://onlinelibrary.wiley.com/doi/10.1111/j.1467-9566.2011.01431.x/abstract.The complex primary and secondary consequences of stroke have often been equated with the concept of biographical disruption, although a number of mediating factors have been identified. However, the research to date is almost exclusively based in western contexts, despite the fact that stroke is increasing most rapidly in low-income and middle-income countries. This research explores the experience of stroke in the rural community of central Aceh, Indonesia. The participants included 11 stroke survivors and 18 carers, with data collected through in-depth interviews and photographic facilitated interviews, supported with participant observation over a nine month period. The participants discussed and illustrated the disruptive result of their stroke, but for most, their ability to maintain religious duties and contribute to their family resulted in a form of biographical continuity. Their strategies and challenges are discussed alongside the implications for care in this context

    "I feel like half my body is clogged up": Lay models of stroke in Central Aceh, Indonesia

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    This is the post-print version of the final paper published in Social Science and Medicine. The published article is available from the link below. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. Copyright @ 2010 Elsevier B.V.Stroke in low and middle income countries is an increasing cause of death and disability, with rates and the estimated burden considerably higher than that of high income countries. Lay explanatory models are believed to be one of the major influences on health seeking behaviour and essential to understand for appropriate education strategies. Despite stroke being a considerable health concern in Indonesia and particularly in Aceh, no studies to date have explored lay stroke models in that context. This paper presents the findings of a qualitative study informed by both hermeneutic phenomenology and ethnography. Based in rural communities in Bener Meriah and Aceh Tengah in Central Aceh, Indonesia, data were gathered through interviews, photographs and observations with 11 persons with stroke (aged 32–69 years) and 18 of their carers. Fieldwork was conducted over nine months between 2007 and 2008. The study examined lay concepts of stroke, described as a condition resulting from a local blockage in blood from multiple causes, many of which are not recognised within the biomedical frame. The blockage is understood to be reversible and therefore the condition curable. This understanding is embedded and sustained in the specific political, cultural, religious and social context. The results illustrate similarities and differences with other cross-cultural studies and suggest areas of future research and points of consideration for stroke education strategies

    Phosphorylation of survivin at threonine 34 inhibits its mitotic function and enhances its cytoprotective activity

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    Survivin is an essential chromosomal passenger protein required for mitotic progression. It is also an inhibitor of apoptosis and can prevent caspase-mediated cell death. In addition, survivin levels are elevated in cancer cells where its presence correlates with increased resistance to chemo- and radio-therapy, which makes it an attractive target for novel anti-cancer strategies. Interestingly, survivin is phosphorylated by the mitotic kinase, cdk1, and a non-phosphorylatable form, survivin(T34A), cannot inhibit apoptosis. Here we rigorously test the ability of survivin(T34A) and its corresponding phosphomimetic, survivin(T34E), to promote cell viability through survivin's dual roles. The effects of these mutations are diametrically opposed: survivin(T34A) accelerates cell proliferation and promotes apoptosis, whereas survivin(T34E) retards growth and promotes survival. Thus the phosphorylation status of survivin at T34 is pivotal to a cell's decision to live or die

    PREVENTION AND TREATMENT IN FOOD SAFETY: AN ANALYSIS OF CONCEPTUAL ISSUES

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    Foodborne illness, damage functions, optimal regulation, Food Consumption/Nutrition/Food Safety,

    Spectra and binding energy predictions of chiral interactions for 7Li

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    Using the no-core shell model approach, we report on the first results for 7Li based on the next-to-next-to-leading order chiral nuclear interaction. Both, two-nucleon and three-nucleon interactions are taken into account. We show that the p-shell nuclei are sensitive to the subleading parts of the chiral interactions including three-nucleon forces. Though chiral interactions are soft, we do not observe overbinding for this p-shell nucleus and find a realistic description for the binding energy, excitation spectrum and radius.Comment: 12 pages, 12 figure
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