Intracerebral infection with dengue-3 virus induces meningoencephalitis and behavioral changes that precede lethality in mice

<p>Abstract</p> <p>Background</p> <p>Dengue, one of the most important arboviral diseases of humans, may cause severe systemic disease. Although dengue virus (DENV) has been considered to be a non-neurotropic virus, dengue infection has been associated recently with a series of neurological syndromes, including encephalitis. In this work, we evaluated behavioral changes and inflammatory parameters in C57BL/6 mice infected with non-adapted dengue virus 3 (DENV-3) genotype I.</p> <p>Methods</p> <p>C57BL/6 mice received 4 × 10³PFU of DENV-3 by an intracranial route. We evaluated the trafficking of leukocytes in brain microvasculature using intravital microscopy, and evaluated chemokine and cytokine profiling by an ELISA test at 3 and 6 days post infection (p.i.). Furthermore, we determined myeloperoxidase activity and immune cell populations, and also performed histopathological analysis and immunostaining for the virus in brain tissue.</p> <p>Results</p> <p>All animals developed signs of encephalitis and died by day 8 p.i. Motor behavior and muscle tone and strength parameters declined at day 7 p.i. We observed increased leukocyte rolling and adhesion in brain microvasculature of infected mice at days 3 and 6 p.i. The infection was followed by significant increases in IFN-γ, TNF-α, CCL2, CCL5, CXCL1, and CXCL2. Histological analysis showed evidence of meningoencephalitis and reactive gliosis. Increased numbers of neutrophils, CD4⁺and CD8⁺T cells were detected in brain of infected animals, notably at day 6 p.i. Cells immunoreactive for anti-NS-3 were visualized throughout the brain.</p> <p>Conclusion</p> <p>Intracerebral infection with non-adapted DENV-3 induces encephalitis and behavioral changes that precede lethality in mice.</p

Abundance analysis of APOGEE spectra for 58 metal-poor stars from the bulge spheroid

The central part of the Galaxy hosts a multitude of stellar populations, including the spheroidal bulge stars, stars moved to the bulge through secular evolution of the bar, inner halo, inner thick disc, inner thin disc, as well as debris from past accretion events. We identified a sample of 58 candidate stars belonging to the stellar population of the spheroidal bulge, and analyse their abundances. The present calculations of Mg, Ca, and Si lines are in agreement with the ASPCAP abundances, whereas abundances of C, N, O, and Ce are re-examined. We find normal α-element enhancements in oxygen, similar to magnesium, Si, and Ca abundances, which are typical of other bulge stars surveyed in the optical in Baade’s Window. The enhancement of [O/Fe] in these stars suggests that they do not belong to accreted debris. No spread in N abundances is found, and none of the sample stars is N-rich, indicating that these stars are not second generation stars originated in globular clusters. Ce instead is enhanced in the sample stars, which points to an s-process origin such as due to enrichment from early generations of massive fast rotating stars, the so-called spinstars.RR acknowledges a CNPq master fellowship. TM acknowledges FAPESP postdoctoral fellowship no. 2018/03480-7. HE acknowledges a CAPES PhD fellowship. A.P.-V. and S.O.S. acknowledge the DGAPA-PAPIIT grant IA103122. SOS acknowledges a FAPESP PhD fellowship no. 2018/22044-3. SOS and MV acknowledge the support of the Deutsche Forschungsgemeinschaft (DFG, project number: 428473034). BB acknowledges grants from FAPESP, CNPq, and CAPES – Financial code 001. J.G.F-T gratefully acknowledges the grant support provided by Proyecto Fondecyt Iniciación No. 11220340, and also from ANID Concurso de Fomento a la Vinculación Internacional para Instituciones de Investigación Regionales (Modalidad corta duración) Proyecto No. FOVI210020, and from the ESO – Government of Chile Joint Committee 2021 (ORP 023/2021). D.G. gratefully acknowledges support from the ANID BASAL project ACE210002. D.G. also acknowledges financial support from the Dirección de Investigación y Desarrollo de la Universidad de La Serena through the Programa de Incentivo a la Investigación de Académicos (PIA-DIDULS). The work of V.M.P. is supported by NOIRLab, which is managed by the Association of Universities for Research in Astronomy (AURA) under a cooperative agreement with the National Science Foundation. MZ was funded by ANID FONDECYT Regular 1191505, ANID Millennium Institute of Astrophysics (MAS) under grant ICN12_009, the ANID BASAL Center for Astrophysics and Associated Technologies (CATA) through grants AFB170002, ACE210002 and FB210003. DM gratefully acknowledges support by the ANID BASAL projects ACE210002 and FB210003 and by Fondecyt Project No. 1220724. RR, BB, TM, HE, SOS, are part of the Brazilian Participation Group (BPG) in the Sloan Digital Sky Survey (SDSS), from the Laboratório Interinstitucional de e-Astronomia – LIneA, Brazil. Funding for the Sloan Digital Sky Survey IV has been provided by the Alfred P. Sloan Foundation, the U.S. Department of Energy Office of Science, and the Participating Institutions. SDSS acknowledges support and resources from the Center for High-Performance Computing at the University of Utah. The SDSS web site is www.sdss.org. SDSS is managed by the Astrophysical Research Consortium for the Participating Institutions of the SDSS Collaboration including the Brazilian Participation Group, the Carnegie Institution for Science, Carnegie Mellon University, Center for Astrophysics | Harvard & Smithsonian (CfA), the Chilean Participation Group, the French Participation Group, Instituto de Astrofísica de Canarias, The Johns Hopkins University, Kavli Institute for the Physics and Mathematics of the Universe (IPMU) / University of Tokyo, the Korean Participation Group, Lawrence Berkeley National Laboratory, Leibniz Institut für Astrophysik Potsdam (AIP), Max-Planck-Institut für Astronomie (MPIA Heidelberg), Max-Planck-Institut für Astrophysik (MPA Garching), Max-Planck-Institut für Extraterrestrische Physik (MPE), National Astronomical Observatories of China, New Mexico State University, New York University, University of Notre Dame, Observatório Nacional / MCTI, The Ohio State University, Pennsylvania State University, Shanghai Astronomical Observatory, United Kingdom Participation Group, Universidad Nacional Autónoma de México, University of Arizona, University of Colorado Boulder, University of Oxford, University of Portsmouth, University of Utah, University of Virginia, University of Washington, University of Wisconsin, Vanderbilt University, and Yale University. This work makes use of data from the European Space Agency (ESA) space mission Gaia. The Gaia mission website is https://www.cosmos.esa.int/gaia. The Gaia archive website is https://archives.esac.esa.int/gaia.Peer reviewe

Genetic mechanisms of critical illness in COVID-19.

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

Open innovation in public management: analysis of the Brazilian action plan for Open Government Partnership

Este estudo objetivou analisar o Plano de Ação brasileiro para o Governo Aberto, baseado na teoria da inovação aberta na gestão pública. Utilizou-se de uma pesquisa documental, com vistas a aprofundar o conhecimento do fenômeno em questão. O documento foi escolhido intencionalmente, por ser exemplo basilar das políticas públicas relacionadas à inovação aberta brasileira. Os resultados mostram que os compromissos firmados pelo governo brasileiro estão consoantes com o processo de inovação aberta pública. As ações previstas no Plano estão especificamente relacionadas a transparência, abertura de dados e preparação do corpo estatal para o processo aberto de inovação. _________________________________________________________________________________________ RESUMEN: Este estudio tuvo como objetivo analizar el Plan de Acción de Brasil para el Gobierno Abierto con base en la teoría de la innovación abierta en la gestión pública. Se utilizó una investigación documental, con el fin de profundizar el conocimiento en el fenómeno en cuestión. El documento fue elegido intencionadamente porque es fundamental para las políticas públicas relacionadas con la innovación abierta brasileña. Los resultados muestran que los compromisos asumidos por el gobierno brasileño son compatibles con el proceso de innovación abierta pública. En concreto, las acciones contenidas en el plan están relacionados con la transparencia, los datos abiertos y preparación de la estructura de gobierno para el proceso abierto de innovación. _________________________________________________________________________________________ ABSTRACT: This study aims to analyze the Brazilian action plan for Open Government, based on the theory of open innovation in public management. Documentary research was used, in order to deepen of the knowledge the phenomenon being discussed . The document was intentionally chosen because it is essential for public policies related to Brazilian open innovation The results show that the commitments made by the Brazilian government are compatible with the public open innovation process. The actions in the Plan are related specifically to transparency, open data and preparation of the governance body for the open innovation process