• McNeil Law posted an update 6 hours, 38 minutes ago

    The coronavirus disease 2019 (COVID-19) remains a global public health emergency. Despite being caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), besides the lung, this infectious disease also has severe implications in cardiovascular system. In this review, we summarize diverse clinical complications of heart and vascular system, as well as the relevant high mortality, in COVID-19 patients. Systemic inflammation and angiotensin-converting enzyme 2-involved signaling networking in SARS-CoV-2 infection and cardiovascular system may contribute to the manifestations of cardiovascular diseases. Therefore, integration of clinical observations and experimental findings can promote our understanding of the underlying mechanisms, which would aid in identifying and treating the cardiovascular injury in patients with COVID-19 appropriately.

    This scoping review aims to map the extent, range and nature of qualitative research on people’s ‘perceptions’ of their own alcohol consumption.

    A systematic search of five electronic databases was conducted. A total of 915 abstracts were screened and 452 full texts examined, of which 313 papers met the inclusion criteria (including a report of qualitative data on perceptions, experiences or views of people’s own drinking in peer-reviewed journals published in English).

    This study maps the available literature assembled over approximately 30 years, which was found to be extensive and diverse. Many existing studies are focused largely on people’s ‘experiences’ of their own drinking behaviours, particularly when they were drinking in ways commonly understood as heavy, risky or problematic. Fewer studies focused on populations whose drinking was not heavy or was risky in less obvious ways, such as older adults prescribed medications for chronic health conditions. Most studies were conducted since 2010, with the rate of publications increasing since 2014.

    This review identifies gaps in the evidence regarding people’s perceptions of their own drinking and opportunities for qualitative studies to make valuable contributions to alcohol research. selleck inhibitor Gaps discussed include patterns of drinking that are less obviously problematic, and in relation to consumption of alcohol in those parts of the world where overall consumption and harms from alcohol are high. Such studies could usefully be informed by existing studies in the evidence mapping.

    This review identifies gaps in the evidence regarding people’s perceptions of their own drinking and opportunities for qualitative studies to make valuable contributions to alcohol research. Gaps discussed include patterns of drinking that are less obviously problematic, and in relation to consumption of alcohol in those parts of the world where overall consumption and harms from alcohol are high. Such studies could usefully be informed by existing studies in the evidence mapping.Using the Moving to Opportunity (MTO) experiment (1994-2002), this study examined how a multidimensional measure of neighborhood quality over time influenced adolescent psychological distress, using instrumental variable (IV) analysis. Neighborhood quality was operationalized with an independently-validated 19-indicator child opportunity index (COI), linked to MTO family addresses over 4-7 years. We examined if being randomized to receive a housing subsidy (versus remaining in public housing) predicted neighborhood quality across time. Using IV analysis, we tested if experimentally induced differences in COI across time predicted psychological distress (N=2829; Mean(standard deviation (SD)) = -.04(1.12)). The MTO voucher treatment improved neighborhood quality for children compared to in-place controls. A one-SD change in COI since baseline predicted 0.32 point lower psychological distress for girls (B(95%CI)= -0.32 (-0.61, -0.03)). Results were comparable but less precisely estimated when operationalizing neighborhood quality as simply average post-random assignment COI, (B(95%CI)= -0.36(-0.74, 0.02). Effect estimates based on a COI excluding poverty and on the most recent COI measure were slightly larger than other operationalizations of neighborhood quality. Improving a multidimensional measure of neighborhood quality led to reductions in low-income girls’ psychological distress, and this was estimated with high internal validity using IV methods.

    Single-cell RNA-sequencing (scRNA-seq) offers the opportunity to dissect heterogeneous cellular compositions and interrogate the cell-type-specific gene expression patterns across diverse conditions. However, batch effects such as laboratory conditions and individual-variability hinder their usage in cross-condition designs.

    Here, we present a single-cell Generative Adversarial Network (scGAN) to simultaneously acquire patterns from raw data while minimizing the confounding effect driven by technical artifacts or other factors inherent to the data. Specifically, scGAN models the data likelihood of the raw scRNA-seq counts by projecting each cell onto a latent embedding. Meanwhile, scGAN attempts to minimize the correlation between the latent embeddings and the batch labels across all cells. We demonstrate scGAN on three public scRNA-seq datasets and show that our method confers superior performance over the state-of-the-art methods in forming clusters of known cell types and identifying known psychiatric genes that are associated with major depressive disorder.

    The scGAN code and the information for the public scRNA-seq datasets are available at https//github.com/li-lab-mcgill/singlecell-deepfeature.

    Supplementary data are available at Bioinformatics online.

    Supplementary data are available at Bioinformatics online.Mitogen activated protein kinase kinases (MAPKKs) are an important part of evolutionary conserved signaling modules that involved in a variety of cellular processes in response to environmental stimuli. Among them, mitogen-activated protein kinase kinase 2 (MEK2) is the most crucial upstream signaling pathway of ERK1/2 cascade as a therapeutic target for overcoming Ras-driven cancers. However, the mechanisms of MEK2 regulation during tumor progression remain not fully elucidated. Herein, we identified that MEK2 was post-translationally regulated by O-GlcNAcylation. We found that MEK2 associated with OGT and was modified by O-GlcNAc. Mass spectrometry analysis further verified that O-GlcNAcylation of MEK2 occurred at Thr13, which was located in the docking domain (DD) for specifically identifying its target proteins. While total O-GlcNAcylation stimulated the protein stability and phosphorylation of MEK2, Thr13 O-GlcNAcylation of MEK2 specifically enhanced its Thr394 phosphorylation as well as downstream ERK1/2 activation.