36 research outputs found

    Sustained IFN signaling is associated with delayed development of SARS-CoV-2-specific immunity.

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    Plasma RNAemia, delayed antibody responses and inflammation predict COVID-19 outcomes, but the mechanisms underlying these immunovirological patterns are poorly understood. We profile 782 longitudinal plasma samples from 318 hospitalized patients with COVID-19. Integrated analysis using k-means reveals four patient clusters in a discovery cohort: mechanically ventilated critically-ill cases are subdivided into good prognosis and high-fatality clusters (reproduced in a validation cohort), while non-critical survivors segregate into high and low early antibody responders. Only the high-fatality cluster is enriched for transcriptomic signatures associated with COVID-19 severity, and each cluster has distinct RBD-specific antibody elicitation kinetics. Both critical and non-critical clusters with delayed antibody responses exhibit sustained IFN signatures, which negatively correlate with contemporaneous RBD-specific IgG levels and absolute SARS-CoV-2-specific B and CD4 <sup>+</sup> T cell frequencies. These data suggest that the "Interferon paradox" previously described in murine LCMV models is operative in COVID-19, with excessive IFN signaling delaying development of adaptive virus-specific immunity

    Using agroecological zones to promote European collaboration in organic farming research.

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    Agro-ecological and other spatial information can be used to improve our understanding of organic farming research issues, inform the application of research from one area to another, and support collaboration and prioritisation within regional research programmes. Of the 25 organic farming research priorities identified by the IFOAM EU Group in 2004, 15 were related to regional differences in agroecological conditions. The other priorities were potentially affected by spatial differences in political, institutional and socio-economic conditions. In relation to agro-ecological data, the capacity to identify i) general agro-ecological areas and ii) areas with specific agro-ecological advantage or stress seems particularly useful. The use of a geographic information system (GIS) to integrate spatial data to identify and display such areas is illustrated with two examples

    Using next-generation sequencing for molecular reconstruction of past arctic vegetation and climate

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    Palaeoenvironments and former climates are typically inferred from pollen and macrofossil records. This approach is time-consuming and suffers from low taxonomic resolution and biased taxon sampling. Here, we test an alternative DNA-based approach utilizing the P6 loop in the chloroplast trnL (UAA) intron; a short (13–158 bp) and variable region with highly conserved flanking sequences. For taxonomic reference, a whole trnL intron sequence database was constructed from recently collected material of 842 species, representing all widespread and/or ecologically important taxa of the species-poor arctic flora. The P6 loop alone allowed identification of all families, most genera (&gt;75%) and one-third of the species, thus providing much higher taxonomic resolution than pollen records. The suitability of the P6 loop for analysis of samples containing degraded ancient DNA from a mixture of species is demonstrated by high-throughput parallel pyrosequencing of permafrost-preserved DNA and reconstruction of two plant communities from the last glacial period. Our approach opens new possibilities for DNA-based assessment of ancient as well as modern biodiversity of many groups of organisms using environmental samples.<br/

    Applied Welfare Economics with Bounded Rationality: Public Policies Toward Remote Sensing

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    Earlier experimental evidence indicates that some decision makers under-invest in information when it is costly. This insight is applied to the cost–benefit analysis of the provision of data obtained by satellites. In fields like agriculture, remotely sensed information of great precision can be provided to additional farmers at minimal extra costs if a service for farmers with similar information needs is set up. Here, the tendency to under-invest in information asks for creative solutions by the private sector: bankers may work together with rational producers in setting up the information service and promoting it. However, if producers’ financial resources are insufficient, public intervention, in the form of a free information service may be necessary. Copyright International Atlantic Economic Society 2005D61, H42,

    A third SARS-CoV-2 mRNA vaccine dose in people receiving hemodialysis overcomes B cell defects but elicits a skewed CD4<sup>+</sup> T cell profile.

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    Cellular immune defects associated with suboptimal responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccination in people receiving hemodialysis (HD) are poorly understood. We longitudinally analyze antibody, B cell, CD4 &lt;sup&gt;+&lt;/sup&gt; , and CD8 &lt;sup&gt;+&lt;/sup&gt; T cell vaccine responses in 27 HD patients and 26 low-risk control individuals (CIs). The first two doses elicit weaker B cell and CD8 &lt;sup&gt;+&lt;/sup&gt; T cell responses in HD than in CI, while CD4 &lt;sup&gt;+&lt;/sup&gt; T cell responses are quantitatively similar. In HD, a third dose robustly boosts B cell responses, leads to convergent CD8 &lt;sup&gt;+&lt;/sup&gt; T cell responses, and enhances comparatively more T helper (T &lt;sub&gt;H&lt;/sub&gt; ) immunity. Unsupervised clustering of single-cell features reveals phenotypic and functional shifts over time and between cohorts. The third dose attenuates some features of T &lt;sub&gt;H&lt;/sub&gt; cells in HD (tumor necrosis factor alpha [TNFα]/interleukin [IL]-2 skewing), while others (CCR6, CXCR6, programmed cell death protein 1 [PD-1], and HLA-DR overexpression) persist. Therefore, a third vaccine dose is critical to achieving robust multifaceted immunity in hemodialysis patients, although some distinct T &lt;sub&gt;H&lt;/sub&gt; characteristics endure
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