17 research outputs found

    Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

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    The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality

    Therapeutic implications of cellular and molecular biology of cancer stem cells in melanoma

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    Phf8 histone demethylase deficiency causes cognitive impairments through the mTOR pathway

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    Mutations in PHF8 gene are genetically associated with X-linked mental retardation. Here, Chen et al. show that Phf8 KO mouse have cognitive and synaptic plasticity impairment, and pharmacological inhibition of mTOR signaling can partially alleviate such defects

    A global review and meta-analysis of applications of the freshwater Fish Invasiveness Screening Kit

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    The freshwater Fish Invasiveness Screening Kit (FISK) has been applied in 35 risk assessment areas in 45 countries across the six inhabited continents (11 applications using FISK v1; 25 using FISK v2). The present study aimed: to assess the breadth of FISK applications and the confidence (certainty) levels associated with the decision-support tool's 49 questions and its ability to distinguish between taxa of low-to-medium and high risk of becoming invasive, and thus provide climate-specific, generalised, calibrated thresholds for risk level categorisation; and to identify the most potentially invasive freshwater fish species on a global level. The 1973 risk assessments were carried out by 70 + experts on 372 taxa (47 of the 51 species listed as invasive in the Global Invasive Species Database ), which in decreasing order of importance belonged to the taxonomic Orders Cypriniformes, Perciformes, Siluriformes, Characiformes, Salmoniformes, Cyprinodontiformes, with the remaining approximate to 8% of taxa distributed across an additional 13 orders. The most widely-screened species (in decreasing importance) were: grass carp Ctenopharyngodon idella, common carp Cyprinus carpio, rainbow trout Oncorhynchus mykiss, silver carp Hypophthalmichthys molitrix and topmouth gudgeon Pseudorasbora parva. Nine 'globally' high risk species were identified: common carp, black bullhead Ameiurus melas, round goby Neogobius melanostomus, Chinese (Amur) sleeper Perccottus glenii, brown bullhead Ameiurus nebulosus, eastern mosquitofish Gambusia holbrooki, largemouth (black) bass Micropterus salmoides, pumpkinseed Lepomis gibbosus and pikeperch Sander lucioperca. The relevance of this global review to policy, legislation, and risk assessment and management procedures is discussed
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