3,552 research outputs found

    Carotenoids and Antioxidant Nutrients following Burn Injury a

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    Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72213/1/j.1749-6632.1993.tb26193.x.pd

    Development and validation of anti-human Alpha synuclein DNA aptamer using computer modelling techniques—an in silico study

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    Biomarker detection strategies have, in recent years, been moving towards nucleic acid-based detection systems in the form of aptamers, short oligonucleotide sequences which have shown promise in pre-clinical and research settings. One such aptamer is M5-15, a DNA aptamer raised against human alpha synuclein (α-syn) the causative agent in Lewy body and Parkinson’s disease (PD) associated dementia. While this aptamer has shown promise, in silico methodologies have demonstrated a capacity to produce aptamers that have higher affinities for their targets than in vitro generated sequences. A Python script random generated library of DNA sequences were screened based on their thermodynamic stability with the use of DINAMelt server-QuickFold web server. The selected sequences were examined with MFold in order to generate secondary structure data that were used to produce 3D data with the use of RNA composer software. Further on, the structure was corrected and RNA was replaced with DNA and the virtual screening for α-syn aptamer took place with a series of molecular docking experiments with the use of CSD-Discovery-GOLD software. Herein we propose an alternative in silico generated aptamer we call TMG-79 which demonstrates greater affinity for the target compared to M5-15 (M5-15 = –15.9 kcal/mol, TMG-79 = –17.77 kcal/mol) as well as better ChemPLP fitness scoring between the top poses (M5-15 = 32.33, TMG-79 = 53.32). Structural analysis suggests that while there are similarities, the greater potential flexibility of TMG-79 could be promoting greater affinity for the α-syn compared to M5-15. In silico methods of aptamer generation has the potential to revolutionise the field of aptamer design. We feel that further development of TMG-79 and validation in vitro will make it a viable candidate for diagnostic and research use in the future

    TMEM16A calcium-activated chloride currents in supporting cells of the mouse olfactory epithelium

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    Glial-like supporting (or sustentacular) cells are important constituents of the olfactory epithelium that are involved in several physiological processes such as production of endocannabinoids, insulin, and ATP and regulation of the ionic composition of the mucus layer that covers the apical surface of the olfactory epithelium. Supporting cells express metabotropic P2Y purinergic receptors that generate ATP-induced Ca2+ signaling through the activation of a PLC-mediated cascade. Recently, we reported that a subpopulation of supporting cells expresses also the Ca2+-activated Cl- channel TMEM16A. Here, we sought to extend our understanding of a possible physiological role of this channel in the olfactory system by asking whether Ca2+ can activate Cl- currents mediated by TMEM16A. We use whole-cell patch-clamp analysis in slices of the olfactory epithelium to measure dose-response relations in the presence of various intracellular Ca2+ concentrations, ion selectivity, and blockage. We find that knockout of TMEM16A abolishes Ca2+-activated Cl- currents, demonstrating that TMEM16A is essential for these currents in supporting cells. Also, by using extracellular ATP as physiological stimuli, we found that the stimulation of purinergic receptors activates a large TMEM16A-dependent Cl- current, indicating a possible role of TMEM16A in ATP-mediated signaling. Altogether, our results establish that TMEM16A-mediated currents are functional in olfactory supporting cells and provide a foundation for future work investigating the precise physiological role of TMEM16A in the olfactory system

    Chronotype and environmental light exposure in a student population

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    In humans and most other species, changes in the intensity and duration of light provide a critical set of signals for the synchronisation of the circadian system to the astronomical day. The timing of activity within the 24 h day defines an individual’s chronotype, i.e. morning, intermediate or evening type. The aim of this study was to investigate the associations between environmental light exposure, due to geographical location, on the chronotype of university students. Over 6 000 university students from cities in the Northern Hemisphere (Oxford, Munich and Groningen) and Southern Hemisphere (Perth, Melbourne and Auckland) completed the Munich ChronoType Questionnaire. In parallel, light measures (daily irradiance, timing of sunrise and sunset) were compiled from satellite or ground stations at each of these locations. Our data shows that later mid-sleep point on free days (corrected for oversleep on weekends MFSsc) is associated with (i) residing further from the equator, (ii) a later sunset, (iii) spending more time outside and (iv) waking from sleep significantly after sunrise. However, surprisingly, MSFscdid not correlate with daily light intensity at the different geographical locations. Although these findings appear to contradict earlier studies suggesting that in the wider population increased light exposure is associated with an earlier chronotype, our findings are derived exclusively from a student population aged between 17 and 26 years. We therefore suggest that the age and occupation of our population increase the likelihood that these individuals will experience relatively little light exposure in the morning whilst encountering more light exposure later in the day, when light has a delaying effect upon the circadian system

    Deconstructing the lesbian, gay, bisexual, transgender victim of sex trafficking: Harm, exceptionality and religion–sexuality tensions

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    Contrary to widespread belief, sex trafficking also targets lesbian, gay, bisexual, transgender (LGBT) communities. Contemporary social and political constructions of victimhood lie at the heart of regulatory policies on sex trafficking. Led by the US Department of State, knowledge about LGBT victims of trafficking constitutes the newest frontier in the expansion of criminalization measures. These measures represent a crucial shift. From a burgeoning range of preemptive measures enacted to protect an amorphous class of ‘all potential victims’, now policies are heavily premised on the risk posed by traffickers to ‘victims of special interest’. These constructed identities, however, are at odds with established structures. Drawing on a range of literatures, the core task of this article is to confront some of the complexities and tensions surrounding constructions of LGBT trafficking victims. Specifically, the article argues that discourses of ‘exceptional vulnerability’ and the polarized notions of ‘innocence’ and ‘guilt’ inform hierarchies of victimhood. Based on these insights, the article argues for the need to move beyond monolithic understandings of victims, by reframing the politics of harm accordingly

    Extended Superscaling of Electron Scattering from Nuclei

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    An extended study of scaling of the first and second kinds for inclusive electron scattering from nuclei is presented. Emphasis is placed on the transverse response in the kinematic region lying above the quasielastic peak. In particular, for the region in which electroproduction of resonances is expected to be important, approximate scaling of the second kind is observed and the modest breaking of it is shown probably to be due to the role played by an inelastic version of the usual scaling variable.Comment: LaTeX, 36 pages including 5 color postscript figures and 4 postscript figure

    What are the mechanisms that support healthcare professionals to adopt assisted decision-making practice? A rapid realist review

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    Background The United Nations Convention on the Rights of Persons with Disabilities (UNCRPD) establishes a right to legal capacity for all people, including those with support needs. People with disabilities have a legal right to be given the appropriate supports to make informed decisions in all aspects of their lives, including health. In Ireland, the Assisted Decision-Making (Capacity) Act (2015) ratifies the Convention and has established a legal framework for Assisted Decision Making (ADM). The main provisions of the Act are not yet implemented. Codes of Practice to guide health and social care professionals are currently being developed. Internationally, concerns are expressed that ADM implementation is poorly understood. Using realist synthesis, this study aims to identify Programme Theory (PT) that will inform ADM implementation in healthcare. Methods A Rapid Realist Review using collaborative methods was chosen to appraise relevant literature and engage knowledge users from Irish health and social care. The review was led by an expert panel of relevant stakeholders that developed the research question which asks, ‘what mechanisms enable healthcare professionals to adopt ADM into practice?’ To ensure the PT was inclusive of local contextual influences, five reference panels were conducted with healthcare professionals, family carers and people with dementia. PT was refined and tested iteratively through knowledge synthesis informed by forty-seven primary studies, reference panel discussions and expert panel refinement and consensus. Results The review has developed an explanatory PT on ADM implementation in healthcare practice. The review identified four implementation domains as significant. These are Personalisation of Health & ADM Service Provision, Culture & Leadership, Environmental & Social Re-structuring and Education, Training & Enablement. Each domain is presented as an explanatory PT statement using realist convention that identifies context, mechanism and outcome configurations. Conclusions This realist review makes a unique contribution to this field. The PT can be applied by policymakers to inform intervention development and implementation strategy. It informs the imminent policy and practice developments in Ireland and has relevance for other worldwide healthcare systems dealing with similar legislative changes in line with UNCRPD

    Constraining the angular momentum evolution of V455 Andromedae

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    Time-series photometry on the cataclysmic variable V455 Andromedae (hereafter V455 And, HS 2331+3905) reveals a rotation period shorter than the orbital period, implying the presence of a magnetic field. We expect that this magnetic field channels the accreted matter from the disk toward the white dwarf poles, classifying it as an Intermediate Polar. The two polar spinning emission areas are visible in the lightcurves at the rotation period of 67.61970396 ± 0.00000072 s, and its harmonic. Using photometric observations of V455 And obtained from 2007 October to 2015, we derive 3σ upper limits to the rate of change of the spin harmonic (SH) with time to be dPSH/dt ≀ −7.5 × 10−15 s s−1 employing the O–C method, and −5.4 × 10−15 s s−1 with a direct nonlinear least squares fit. There is no significant detection of a changing spin period for the duration of 2007 October–2015. The 3σ upper limit for the rate of change of spin period with time is dPspin/dt ≀ −10.8 × 10−15 s s−1 or −0.34 ÎŒs yr−1. V455 And underwent a large-amplitude dwarf nova outburst in 2007 September. The pre-outburst data reflect a period 4.8 ± 2.2 ÎŒs longer than the best-fit post-outburst spin period. The angular momentum gained by the white dwarf from matter accreted during outburst and its slight subsequent shrinking should both cause the star to spin slightly faster after the outburst. We estimate that the change in spin period due to the outburst should be 5 ÎŒs, consistent with the empirical determination of 4.8 ± 2.2 ÎŒs (3σ upper limit of 11.4 ÎŒs)
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