548 research outputs found

    An Stomatin, Prohibitin, Flotillin, and HflK/C-Domain Protein Required to Link the Phage-Shock Protein to the Membrane in Bacillus subtilis

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    Membrane surveillance and repair is of utmost importance to maintain cellular integrity and allow cellular life. Several systems detect cell envelope stress caused by antimicrobial compounds and abiotic stresses such as solvents, pH-changes and temperature in bacteria. Proteins containing an Stomatin, Prohibitin, Flotillin, and HflK/C (SPFH)-domain, including bacterial flotillins have been shown to be involved in membrane protection and membrane fluidity regulation. Here, we characterize a bacterial SPFH-domain protein, YdjI that is part of a stress induced complex in Bacillus subtilis. We show that YdjI is required to localize the ESCRT-III homolog PspA to the membrane with the help of two membrane integral proteins, YdjG/H. In contrast to classical flotillins, YdjI resides in fluid membrane regions and does not enrich in detergent resistant membrane fractions. However, similarly to FloA and FloT from B. subtilis, deletion of YdjI decreases membrane fluidity. Our data reveal a hardwired connection between phage shock response and SPFH proteins

    A validation of the religious and spiritual struggles scale among young people living with HIV in Zimbabwe: Mokken scale analysis and exploratory factor analysis.

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    INTRODUCTION Religious/spiritual convictions and practices can influence health- and treatment-seeking behavior, but only few measures of religiousness or spirituality have been validated and used outside of the US. The Religious and Spiritual Struggles scale (RSS) measures internal and external conflict with religion and spirituality and has been validated mainly in different high-income contexts. The aim of this study was the validation of the RSS in the Zimbabwean context and among young people living with human immunodeficiency virus (YPLHIV) aged 14-24. METHODS Data collection with an Open Data Kit (ODK) questionnaire with 804 respondents took place in 2021. The validation was performed by confirmatory factor analysis (CFA), using statistical equation modeling (SEM), and Mokken scale analysis (MSA). After the low confirmability of the original scale sub-dimensions exploratory factor analysis (EFA) was applied. RESULTS The EFA resulted in four new sub-domains that were different from the original six domains in the RSS but culturally more relevant. The new sub-domains are significantly related to health. DISCUSSION The findings support the validity and relevance of the RSS and the new sub-domains in this context. As our study was limited to YPLHIV, further validation of the RSS among different population groups and contexts in the sub-Saharan region is encouraged

    Prospects for High-Elevation Radio Detection of >100 PeV Tau Neutrinos

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    Tau neutrinos are expected to comprise roughly one third of both the astrophysical and cosmogenic neutrino flux, but currently the flavor ratio is poorly constrained and the expected flux at energies above 101710^{17} eV is low. We present a detector concept aimed at measuring the diffuse flux of tau neutrinos in this energy range via a high-elevation mountaintop detector using the radio technique. The detector searches for radio signals from upgoing air showers generated by Earth-skimming tau neutrinos. Signals from several antennas in a compact array are coherently summed at the trigger level, permitting not only directional masking of anthropogenic backgrounds, but also a low trigger threshold. This design takes advantage of both the large viewing area available at high-elevation sites and the nearly full duty cycle available to radio instruments. We present trade studies that consider the station elevation, frequency band, number of antennas in the array, and the trigger threshold to develop a highly efficient station design. Such a mountaintop detector can achieve a factor of ten improvement in acceptance over existing instruments with 100 independent stations. With 1000 stations and three years of observation, it can achieve a sensitivity to an integrated E2\mathcal{E}^{-2} flux of <109<10^{-9} GeV cm2^{-2} sr1^{-1} s1^{-1}, in the range of the expected flux of all-flavor cosmogenic neutrinos assuming a pure iron cosmic-ray composition.Comment: 26 pages, 11 figure

    Evidence-based Toxicology for the 21st Century: Opportunities and Challenges

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    The Evidence-based Toxicology Collaboration (EBTC) was established recently to translate evidence-based approaches from medicine and health care to toxicology in an organized and sustained effort. The EBTC held a workshop on “Evidence-based Toxicology for the 21st Century: Opportunities and Challenges” in Research Triangle Park, North Carolina, USA on January 24-25, 2012. The presentations largely reflected two EBTC priorities: to apply evidence-based methods to assessing the performance of emerging pathwaybased testing methods consistent with the 2007 National Research Council report on “Toxicity Testing in the 21st Century” as well as to adopt a governance structure and work processes to move that effort forward. The workshop served to clarify evidence-based approaches and to provide food for thought on substantive and administrative activities for the EBTC. Priority activities include conducting pilot studies to demonstrate the value of evidence-based approaches to toxicology, as well as conducting educational outreach on these approaches

    Evidence-based Toxicology for the 21st Century: Opportunities and Challenges

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    The Evidence-based Toxicology Collaboration (EBTC) was established recently to translate evidence-based approaches from medicine and health care to toxicology in an organized and sustained effort. The EBTC held a workshop on “Evidence-based Toxicology for the 21st Century: Opportunities and Challenges” in Research Triangle Park, North Carolina, USA on January 24-25, 2012. The presentations largely reflected two EBTC priorities: to apply evidence-based methods to assessing the performance of emerging pathwaybased testing methods consistent with the 2007 National Research Council report on “Toxicity Testing in the 21st Century” as well as to adopt a governance structure and work processes to move that effort forward. The workshop served to clarify evidence-based approaches and to provide food for thought on substantive and administrative activities for the EBTC. Priority activities include conducting pilot studies to demonstrate the value of evidence-based approaches to toxicology, as well as conducting educational outreach on these approaches

    Is this photograph taken? - The active (act of) collaboration with photography

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    Over more than thirty years of commercial and fine art photographic practice, I have often noticed remarkable disparities between the scenes, objects, events or moments ‘out there’ I had attempted to record – and the images within the resulting photographs. These (sometimes subtle, sometimes profound, but rarely anticipatable) disparities between what I had seen and what the photograph shows me offer the tantalising suggestion that there may be something else going on here – but something which the popular conception of photography may hinder our ability to recognise. This article explores the implications of four central assumptions implicit within the popular conception of photography which may impede new ways of thinking about photographic practice. Supported by a number of photographs that depict scenes, events and ‘moments’ which were not ‘taken’ but were created by the act of photographing them, I will suggest that new opportunities for practice may be available by ‘re-imagining’ the practice of photography as an active – or, as an act of – collaboration between medium and practitioner

    Pelvic and breast examination skills curricula in United States medical schools: a survey of obstetrics and gynecology clerkship directors

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    Background: Learning to perform pelvic and breast examinations produces anxiety for many medical students. Clerkship directors have long sought strategies to help students become comfortable with the sensitive nature of these examinations. Incorporating standardized patients, simulation and gynecologic teaching associates (GTAs) are approaches gaining widespread use. However, there is a paucity of literature guiding optimal approach and timing. Our primary objective was to survey obstetrics and gynecology (Ob/Gyn) clerkship directors regarding timing and methods for teaching and assessment of pelvic and breast examination skills in United States medical school curricula, and to assess clerkship director satisfaction with current educational strategies at their institutions. Methods: Ob/Gyn clerkship directors from all 135 Liaison Committee on Medical Education accredited allopathic United States medical schools were invited to complete an anonymous 15-item web-based questionnaire. Results: The response rate was 70%. Pelvic and breast examinations are most commonly taught during the second and third years of medical school. Pelvic examinations are primarily taught during the Ob/Gyn and Family Medicine (FM) clerkships, while breast examinations are taught during the Ob/Gyn, Surgery and FM clerkships. GTAs teach pelvic and breast examinations at 72 and 65% of schools, respectively. Over 60% of schools use some type of simulation to teach examination skills. Direct observation by Ob/Gyn faculty is used to evaluate pelvic exam skills at 87% of schools and breast exam skills at 80% of schools. Only 40% of Ob/Gyn clerkship directors rated pelvic examination training as excellent, while 18% rated breast examination training as excellent. Conclusions: Pelvic and breast examinations are most commonly taught during the Ob/Gyn clerkship using GTAs, simulation trainers and clinical patients, and are assessed by direct faculty observation during the Ob/Gyn clerkship. While the majority of Ob/Gyn clerkship directors were not highly satisfied with either pelvic or breast examination training programs, they were less likely to describe their breast examination training programs as excellent as compared to pelvic examination training—overall suggesting an opportunity for improvement. The survey results will be useful in identifying future challenges in teaching such skills in a cost-effective manner. Electronic supplementary material The online version of this article (doi:10.1186/s12909-016-0835-6) contains supplementary material, which is available to authorized users

    The Effects of NMDA Subunit Composition on Calcium Influx and Spike Timing-Dependent Plasticity in Striatal Medium Spiny Neurons

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    Calcium through NMDA receptors (NMDARs) is necessary for the long-term potentiation (LTP) of synaptic strength; however, NMDARs differ in several properties that can influence the amount of calcium influx into the spine. These properties, such as sensitivity to magnesium block and conductance decay kinetics, change the receptor's response to spike timing dependent plasticity (STDP) protocols, and thereby shape synaptic integration and information processing. This study investigates the role of GluN2 subunit differences on spine calcium concentration during several STDP protocols in a model of a striatal medium spiny projection neuron (MSPN). The multi-compartment, multi-channel model exhibits firing frequency, spike width, and latency to first spike similar to current clamp data from mouse dorsal striatum MSPN. We find that NMDAR-mediated calcium is dependent on GluN2 subunit type, action potential timing, duration of somatic depolarization, and number of action potentials. Furthermore, the model demonstrates that in MSPNs, GluN2A and GluN2B control which STDP intervals allow for substantial calcium elevation in spines. The model predicts that blocking GluN2B subunits would modulate the range of intervals that cause long term potentiation. We confirmed this prediction experimentally, demonstrating that blocking GluN2B in the striatum, narrows the range of STDP intervals that cause long term potentiation. This ability of the GluN2 subunit to modulate the shape of the STDP curve could underlie the role that GluN2 subunits play in learning and development
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