603 research outputs found

    Human Genomics of COVID-19 Pneumonia: Contributions of Rare and Common Variants.

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    SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) infection is silent or benign in most infected individuals, but causes hypoxemic COVID-19 pneumonia in about 10% of cases. We review studies of the human genetics of life-threatening COVID-19 pneumonia, focusing on both rare and common variants. Large-scale genome-wide association studies have identified more than 20 common loci robustly associated with COVID-19 pneumonia with modest effect sizes, some implicating genes expressed in the lungs or leukocytes. The most robust association, on chromosome 3, concerns a haplotype inherited from Neanderthals. Sequencing studies focusing on rare variants with a strong effect have been particularly successful, identifying inborn errors of type I interferon (IFN) immunity in 1-5% of unvaccinated patients with critical pneumonia, and their autoimmune phenocopy, autoantibodies against type I IFN, in another 15-20% of cases. Our growing understanding of the impact of human genetic variation on immunity to SARS-CoV-2 is enabling health systems to improve protection for individuals and populations

    Constraints on planetary tidal dissipation from a detailed study of Kepler 91b

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    Context. With the detection of thousands of exoplanets, characterising their dynamical evolution in detail represents a key step in the understanding of their formation. Studying the dissipation of tides occurring both in the host star and in the planets is of great relevance in order to investigate the distribution of the angular momentum occurring among the objects populating the system and to studying the evolution of the orbital parameters. From a theoretical point of view, the dissipation of tides throughout a body may be studied by relying on the so-called phase or time-lag equilibrium tides model in which the reduced tidal quality factor Q'p, or equivalently the product between the love number and the time lag (k2DeltaT), describe how efficiently tides are dissipated within the perturbed body. Constraining these factors by looking at the current configuration of the exoplanetary system is extremely challenging, and simulations accounting for the evolution of the system as a whole might help to shed some light on the mechanisms governing this process. Aims. We aim to constrain the tidal dissipation factors of hot-Jupiter-like planets by studying the orbital evolution of Kepler-91b. Methods. We firstly carried out a detailed asteroseismc characterisation of Kepler-91 and computed a dedicated stellar model using both classical and astereoseismic constraints. We then coupled the evolution of the star to the one of the planets by means of our orbital evolution code and studied the evolution of the system by accounting for tides dissipated both in the planet and in the host star. Results. We found that the maximum value for k2DeltaT (or equivalently the minimum value for Q'p) determining the efficiency of equilibrium tides dissipation occurring within Kepler-91b is 0.4 pm 0.25 s (4.5+5.8 * 10^5).Comment: accepted for publication in Astronomy & Astrophysic

    LOS OBSTÁCULOS QUE ENFRENTAN LOS ESTUDIANTES EN EL PRIMER AÑO UNIVERSITARIO Y LAS ESTRATEGIAS CONSTRUIDAS PARA AFRONTARLOS

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    El presente trabajo, resume los avances del proyecto de investigación “Los obstáculos que enfrentan los estudiantes en el primer año universitario y las estrategias construidas para afrontarlos. El caso de la Facultad de Humanidades, Artes y Ciencias Sociales, sede Concepción del Uruguay (UADER), un estudio cualitativo”1 Partimos de suponer que, si logramos conjugar diferentes miradas a la problemática del acceso y la permanencia a través de lo que nos expresen los propios sujetos involucrados, podremos identificar aspectos tanto psicosociales, sociodinámicos e institucionales que entorpecen o facilitan la permanencia. Esto permitirá superar nuestras propias apreciaciones como docentes sobre los alumnos: “los estudiantes no saben leer, no se entiende lo que escriben”, “no se motivan”, “no entienden las consignas”; pero, además, las valoraciones que hacen los mismos estudiantes respecto de los docentes y del proceso académico en general: “no entendemos cuando el profesor explica”, “no sé cómo hacer con tanto que nos dan para estudiar”, “¿para qué me sirve tal o cual asignatura?”. Para ello no podemos circunscribir la problemática a las dificultades de aprendizaje específicas como la lectura, escritura, comprensión de textos, sino a todas aquellas cuestiones tanto internas como externas al sujeto que pueden incidir en el surgimiento de problemáticas que afectan el desarrollo del proceso de enseñanza- aprendizaje

    Young and Early Career Investigators: Report from a Global HIV Vaccine Enterprise Working Group

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    The scientific challenges facing HIV-1 vaccine development are unprecedented in the history of vaccinology. As a result, investigators, funders, and other stakeholders generally agree that “game-changing” ideas are required. While innovation can certainly arise from investigators at all career stages, young and early-career investigators, defined as those under 40 years of age or within 10 years of their final degree or clinical training, are especially key contributors of novel and transformative ideas. Young and early-career investigators bring energy, enthusiasm, and fresh perspectives that are unbiased by prevailing dogma and that are essential to scientific progress

    Virosaurus A Reference to Explore and Capture Virus Genetic Diversity.

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    The huge genetic diversity of circulating viruses is a challenge for diagnostic assays for emerging or rare viral diseases. High-throughput technology offers a new opportunity to explore the global virome of patients without preconception about the culpable pathogens. It requires a solid reference dataset to be accurate. Virosaurus has been designed to offer a non-biased, automatized and annotated database for clinical metagenomics studies and diagnosis. Raw viral sequences have been extracted from GenBank, and cleaned up to remove potentially erroneous sequences. Complete sequences have been identified for all genera infecting vertebrates, plants and other eukaryotes (insect, fungus, etc.). To facilitate the analysis of clinically relevant viruses, we have annotated all sequences with official and common virus names, acronym, genotypes, and genomic features (linear, circular, DNA, RNA, etc.). Sequences have been clustered to remove redundancy at 90% or 98% identity. The analysis of clustering results reveals the state of the virus genetic landscape knowledge. Because herpes and poxviruses were under-represented in complete genomes considering their potential diversity in nature, we used genes instead of complete genomes for those in Virosaurus

    COVID-19 epidemic in Switzerland: on the importance of testing, contact tracing and isolation.

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    Switzerland is among the countries with the highest number of coronavirus disease-2019 (COVID-19) cases per capita in the world. There are likely many people with undetected SARS-CoV-2 infection because testing efforts are currently not detecting all infected people, including some with clinical disease compatible with COVID-19. Testing on its own will not stop the spread of SARS-CoV-2. Testing is part of a strategy. The World Health Organization recommends a combination of measures: rapid diagnosis and immediate isolation of cases, rigorous tracking and precautionary self-isolation of close contacts. In this article, we explain why the testing strategy in Switzerland should be strengthened urgently, as a core component of a combination approach to control COVID-19

    The Search for Host Genetic Factors of HIV/AIDS Pathogenesis in the Post-Genome Era: Progress to Date and New Avenues for Discovery

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    Though pursuit of host genetic factors that influence the pathogenesis of HIV began over two decades ago, progress has been slow. Initial genome-level searches for variations associated with HIV-related traits have yielded interesting candidates, but less in the way of novel pathways to be exploited for therapeutic targets. More recent genome-wide association studies (GWAS) that include different phenotypes, novel designs, and that have examined different population characteristics suggest novel targets and affirm the utility of additional searches. Recent findings from these GWAS are reviewed, new directions for research are identified, and the promise of systems biology to yield novel insights is discussed

    A comprehensive assessment of demographic, environmental, and host genetic associations with gut microbiome diversity in healthy individuals.

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    BACKGROUND: The gut microbiome is an important determinant of human health. Its composition has been shown to be influenced by multiple environmental factors and likely by host genetic variation. In the framework of the Milieu Intérieur Consortium, a total of 1000 healthy individuals of western European ancestry, with a 1:1 sex ratio and evenly stratified across five decades of life (age 20-69), were recruited. We generated 16S ribosomal RNA profiles from stool samples for 858 participants. We investigated genetic and non-genetic factors that contribute to individual differences in fecal microbiome composition. RESULTS: Among 110 demographic, clinical, and environmental factors, 11 were identified as significantly correlated with α-diversity, ß-diversity, or abundance of specific microbial communities in multivariable models. Age and blood alanine aminotransferase levels showed the strongest associations with microbiome diversity. In total, all non-genetic factors explained 16.4% of the variance. We then searched for associations between > 5 million single nucleotide polymorphisms and the same indicators of fecal microbiome diversity, including the significant non-genetic factors as covariates. No genome-wide significant associations were identified after correction for multiple testing. A small fraction of previously reported associations between human genetic variants and specific taxa could be replicated in our cohort, while no replication was observed for any of the diversity metrics. CONCLUSION: In a well-characterized cohort of healthy individuals, we identified several non-genetic variables associated with fecal microbiome diversity. In contrast, host genetics only had a negligible influence. Demographic and environmental factors are thus the main contributors to fecal microbiome composition in healthy individuals. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT01699893
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