31 research outputs found

    The transcription factor Zeb2 regulates development of conventional and plasmacytoid DCs by repressing Id2

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    Plasmacytoid dendritic cells (DCs [pDCs]) develop from pre-pDCs, whereas two lineages of conventional DCs (cDCs; cDC1s and cDC2s) develop from lineage-committed pre-cDCs. Several transcription factors (TFs) have been implicated in regulating the development of pDCs (E2-2 and Id2) and cDC1s (Irf8, Id2, and Batf3); however, those required for the early commitment of pre-cDCs toward the cDC2 lineage are unknown. Here, we identify the TF zinc finger E box-binding homeobox 2 (Zeb2) to play a crucial role in regulating DC development. Zeb2 was expressed from the pre-pDC and pre-cDC stage onward and highly expressed in mature pDCs and cDC2s. Mice conditionally lacking Zeb2 in CD11c(+) cells had a cell-intrinsic reduction in pDCs and cDC2s, coupled with an increase in cDC1s. Conversely, mice in which CD11c(+) cells overexpressed Zeb2 displayed a reduction in cDC1s. This was accompanied by altered expression of Id2, which was up-regulated in cDC2s and pDCs from conditional knock-out mice. Zeb2 chromatin immunoprecipitation analysis revealed Id2 to be a direct target of Zeb2. Thus, we conclude that Zeb2 regulates commitment to both the cDC2 and pDC lineages through repression of Id2

    Genetic mechanisms of critical illness in COVID-19.

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    Host-mediated lung inflammation is present1, and drives mortality2, in the critical illness caused by coronavirus disease 2019 (COVID-19). Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development3. Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units. We have identified and replicated the following new genome-wide significant associations: on chromosome 12q24.13 (rs10735079, P = 1.65 × 10-8) in a gene cluster that encodes antiviral restriction enzyme activators (OAS1, OAS2 and OAS3); on chromosome 19p13.2 (rs74956615, P = 2.3 × 10-8) near the gene that encodes tyrosine kinase 2 (TYK2); on chromosome 19p13.3 (rs2109069, P = 3.98 ×  10-12) within the gene that encodes dipeptidyl peptidase 9 (DPP9); and on chromosome 21q22.1 (rs2236757, P = 4.99 × 10-8) in the interferon receptor gene IFNAR2. We identified potential targets for repurposing of licensed medications: using Mendelian randomization, we found evidence that low expression of IFNAR2, or high expression of TYK2, are associated with life-threatening disease; and transcriptome-wide association in lung tissue revealed that high expression of the monocyte-macrophage chemotactic receptor CCR2 is associated with severe COVID-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms and mediators of inflammatory organ damage in COVID-19. Both mechanisms may be amenable to targeted treatment with existing drugs. However, large-scale randomized clinical trials will be essential before any change to clinical practice

    More Than Skin Deep: The Impact of Self-Esteem, Desire for Lighter Skin, and Gender on the Mental Health of University Students in Thailand

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    The present study examined the impact of self-esteem, the desire for lighter skin, and gender on levels of depression, anxiety, and stress among university students in Thailand. The study included 761 students from two universities in a northeastern province of Thailand who participated voluntarily. Results indicated that although the desire for lighter skin is prevalent among Thai university students, this desire alone does not significantly impact levels of depression, anxiety, or stress. Self-esteem was a significant predictor of depression, anxiety, and stress. School year showed a significant positive correlation with depression, anxiety, and stress. Academic performance as measured by GPA showed a significant positive correlation with self-esteem and a significant negative correlation with depression. Mental health professionals are advised to explore ways to improve Thai university students’ self-esteem and to examine the influence of academic and graduation-related pressures in order to positively impact students’ overall mental health. Additional implications, limitations, and recommendations for future research are discussed

    Parameterizing tidal creek morphology in mature saltmarshes using semi-automated extraction from lidar

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    Coastal saltmarshes provide a range of ecosystem services, such as flood protection and carbon sequestration, but face rapid global losses. Managed realignment (MR) is an increasingly popular method to artificially recreate these habitats by reinstating tidal regimes to reclaimed land. However, to improve MR design, better knowledge of the processes that control morphological evolution in natural saltmarshes is needed. In this paper, we develop tools to assist in the monitoring of creek network evolution towards dynamic morphological equilibrium, a state of landform stability under current physical forcings. Using lidar (Light Detection and Ranging) datasets, we combined a semi-automated creek extraction algorithm, based on elevation and slope thresholds, with a novel algorithm for morphometric creek analysis. A comprehensive suite of morphological creek characteristics was extracted for 13 natural British saltmarshes, including: amplitude, length, sinuosity ratio, junction angle, width, depth, cross-sectional area, creek order, bifurcation ratio, drainage density, and drainage efficiency. Results closely matched with field-validated manual digitization results, and were significantly faster and less subjective to produce. Morphological equilibrium relationships from the literature were found to be applicable to the new dataset, despite yielding high prediction errors due to the inherent variety of creek network shapes in saltmarshes. New equilibrium relationships were also defined relating the creek network drainage efficiency to the mouth cross-sectional area and the marsh elevation. To improve future scheme designs, these tools will be used in further studies to monitor rates of evolution towards equilibrium in MR sites depending on their initial conditions

    Potential of Microneedle Systems for COVID-19 Vaccination: Current Trends and Challenges

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    To prevent the coronavirus disease 2019 (COVID-19) pandemic and aid restoration to prepandemic normality, global mass vaccination is urgently needed. Inducing herd immunity through mass vaccination has proven to be a highly effective strategy for preventing the spread of many infectious diseases, which protects the most vulnerable population groups that are unable to develop immunity, such as people with immunodeficiencies or weakened immune systems due to underlying medical or debilitating conditions. In achieving global outreach, the maintenance of the vaccine potency, transportation, and needle waste generation become major issues. Moreover, needle phobia and vaccine hesitancy act as hurdles to successful mass vaccination. The use of dissolvable microneedles for COVID-19 vaccination could act as a major paradigm shift in attaining the desired goal to vaccinate billions in the shortest time possible. In addressing these points, we discuss the potential of the use of dissolvable microneedles for COVID-19 vaccination based on the current literature

    Dataset: Morphological evolution of creek networks in 10 restored coastal wetlands in the UK

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    This dataset supports the publication: Chirol, C. et al (2022). Morphological evolution of creek networks in 10 restored coastal wetlands in the UK in Scientific Data.</span
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