621 research outputs found

    DNA repair and resistence to UV-B radiation in western spotted frogs

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    assessed DNA repair and resistance to solar radiation in eggs of members of the western spotted frog complex (Rana pretiosa and R. luteiventris), species whose populations are suffering severe range reductions and declines. Specifically, we measured the activity of photoreactivating enzyme (photolyase) in oocytes of spotted frogs. In some species, photoreactivation is the most important mechanism for repair of UV-damaged DNA. Using field experiments, we also compared the hatching success of spotted frog embr yos at natural oviposition sites at three elevations, where some embr yos were subjected to ambient levels of UV-B radiation and others were shielded from UV-B radiation. Compared with other amphibians, photolyase activities in spotted frogs were relatively high. At all sites, hatching success was unaffected by UV-B. Our data support the interpretation that amphibian embr yos with relatively high levels of photolyase are more resistant to UV-B radiation than those with lower levels of photolyase. At the embr yonic stage, UV-B radiation does not presently seem to be contributing to the population declines of spotted frogs.Peer reviewe

    A multicentre, randomised controlled trial of PDSAFE, a physiotherapist-delivered fall prevention programme for people with Parkinson’s

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    This is the author accepted manuscript. The final version is available from BMJ Publishing Group via the DOI in this record.Objective: To estimate the effect of a physiotherapist-delivered fall-prevention programme for people with Parkinson’s (PwP). Methods: People at risk of falls with confirmed Parkinson’s were recruited to this multi-centre, pragmatic, investigator blind, individually randomised controlled trial with pre-specified sub-group analyses. 474 PwP (Hoehn and Yahr 1-4) were randomised: 238 allocated to a physiotherapy programme and 236 to control. All participants had routine care; the control group received a DVD about Parkinson’s and single advice session at trial completion. The intervention group (PDSAFE) had an individually tailored, progressive home-based fall-avoidance strategy training programme with balance and strengthening exercises. The primary outcome was risk of repeat-falling, collected by self-report monthly diaries, 0 to 6 months post-randomisation. Secondary outcomes included, Mini-BESTest for balance, chair stand test, Falls Efficacy, freezing of gait, health related quality of life (Euroqol EQ-5D), Geriatric Depression Scale, Physical Activity Scale for the Elderly and Parkinson’s disease Questionnaire, fractures and rate of near-falling. Results: Average age, 72 years and 266 (56%) were men. By 6 months 116 (55%) of the control group, and 125 (61.5%) of the intervention group reported repeat falls (controlled odds ratio 1.21, 95% confidence interval 0.74 to 1.98, P=0.447). Secondary sub-group analyses suggested a different response to the intervention between moderate and severe disease severity groups. Balance, falls efficacy and chair stand time improved with near-falls reduced in the intervention arm. Conclusion: PDSAFE did not reduce falling in this pragmatic trial of PwP. Other functional tasks improved and reduced fall rates were apparent among those with moderate disease.Department of HealthNational Institute for Health Research (NIHR

    The cyclin-dependent kinase inhibitor p57(Kip2) is epigenetically regulated in carboplatin resistance and results in collateral sensitivity to the CDK inhibitor seliciclib in ovarian cancer

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    Carboplatin remains a first-line agent in the management of epithelial ovarian cancer (EOC). Unfortunately, platinum-resistant disease ultimately occurs in most patients. Using a novel EOC cell line with acquired resistance to carboplatin: PEO1CarbR, genome-wide micro-array profiling identified the cyclin-dependent kinase inhibitor p57(Kip2) as specifically downregulated in carboplatin resistance. Presently, we describe confirmation of these preliminary data with a variety of approaches

    Questioning policy, youth participation and lifestyle sports

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    Young people have been identified as a key target group for whom participation in sport and physical activity could have important benefits to health and wellbeing and consequently have been the focus of several government policies to increase participation in the UK. Lifestyle sports represent one such strategy for encouraging and sustaining new engagements in sport and physical activity in youth groups, however, there is at present a lack of understanding of the use of these activities within policy contexts. This paper presents findings from a government initiative which sought to increase participation in sport for young people through provision of facilities for mountain biking in a forest in south-east England. Findings from qualitative research with 40 young people who participated in mountain biking at the case study location highlight the importance of non-traditional sports as a means to experience the natural environments through forms of consumption which are healthy, active and appeal to their identities. In addition, however, the paper raises questions over the accessibility of schemes for some individuals and social groups, and the ability to incorporate sports which are inherently participant-led into state-managed schemes. Lifestyle sports such as mountain biking involve distinct forms of participation which present a challenge for policy-makers who seek to create and maintain sustainable communities of youth participants

    Strong negative self regulation of Prokaryotic transcription factors increases the intrinsic noise of protein expression

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    Background Many prokaryotic transcription factors repress their own transcription. It is often asserted that such regulation enables a cell to homeostatically maintain protein abundance. We explore the role of negative self regulation of transcription in regulating the variability of protein abundance using a variety of stochastic modeling techniques. Results We undertake a novel analysis of a classic model for negative self regulation. We demonstrate that, with standard approximations, protein variance relative to its mean should be independent of repressor strength in a physiological range. Consequently, in that range, the coefficient of variation would increase with repressor strength. However, stochastic computer simulations demonstrate that there is a greater increase in noise associated with strong repressors than predicted by theory. The discrepancies between the mathematical analysis and computer simulations arise because with strong repressors the approximation that leads to Michaelis-Menten-like hyperbolic repression terms ceases to be valid. Because we observe that strong negative feedback increases variability and so is unlikely to be a mechanism for noise control, we suggest instead that negative feedback is evolutionarily favoured because it allows the cell to minimize mRNA usage. To test this, we used in silico evolution to demonstrate that while negative feedback can achieve only a modest improvement in protein noise reduction compared with the unregulated system, it can achieve good improvement in protein response times and very substantial improvement in reducing mRNA levels. Conclusions Strong negative self regulation of transcription may not always be a mechanism for homeostatic control of protein abundance, but instead might be evolutionarily favoured as a mechanism to limit the use of mRNA. The use of hyperbolic terms derived from quasi-steady-state approximation should also be avoided in the analysis of stochastic models with strong repressors

    Dementia and detectives: Alzheimer's disease in crime fiction

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    Fictional representations of dementia have burgeoned in recent years, and scholars have amply explored their double-edged capacity to promote tragic perspectives or normalising images of ‘living well’ with the condition. Yet to date, there has been only sparse consideration of the treatment afforded dementia within the genre of crime fiction. Focusing on two novels, Emma Healey’s Elizabeth is Missing and Alice LaPlante’s Turn of Mind, this article considers what it means in relation to the ethics of representation that these authors choose to cast as their amateur detective narrators women who have dementia. Analysing how their narrative portrayals frame the experience of living with dementia, it becomes apparent that features of the crime genre inflect the meanings conveyed. While aspects of the novels may reinforce problem-based discourses around dementia, in other respects they may spur meaningful reflection about it among the large readership of this genre
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