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

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

The regulation of brain states by neuroactive substances distributed via the cerebrospinal fluid; a review.

Contains fulltext : 83842.pdf (publisher's version ) (Open Access)The cerebrospinal fluid (CSF) system provides nutrients to and removes waste products from the brain. Recent findings suggest, however, that in addition, the CSF contains message molecules in the form of actively released neuroactive substances. The concentrations of these vary between locations, suggesting they are important for the changes in brain activity that underlie different brain states, and induce different sensory input and behavioral output relationships.The cranial CSF displays a rapid caudally-directed ventricular flow followed by a slower rostrally-directed subarachnoid flow (mainly towards the cribriform plate and from there into the nasal lymphatics). Thus, many brain areas are exposed to and can be influenced by substances contained in the CSF. In this review we discuss the production and flow of the CSF, including the mechanisms involved in the regulation of its composition. In addition, the available evidence for the release of neuropeptides and other neuroactive substances into the CSF is reviewed, with particular attention to the selective effects of these on distant downstream receptive brain areas. As a conclusion we suggest that (1) the flowing CSF is involved in more than just nutrient and waste control, but is also used as a broadcasting system consisting of coordinated messages to a variety of nearby and distant brain areas; (2) this special form of volume transmission underlies changes in behavioral states

Novel genes and sex differences in COVID-19 severity.

Here we describe the results of a genome-wide study conducted in 11 939 COVID-19 positive cases with an extensive clinical information that were recruited from 34 hospitals across Spain (SCOURGE consortium). In sex-disaggregated genome-wide association studies for COVID-19 hospitalization, genome-wide significance (p < 5x10-8) was crossed for variants in 3p21.31 and 21q22.11 loci only among males (p = 1.3x10-22 and p = 8.1x10-12, respectively), and for variants in 9q21.32 near TLE1 only among females (p = 4.4x10-8). In a second phase, results were combined with an independent Spanish cohort (1598 COVID-19 cases and 1068 population controls), revealing in the overall analysis two novel risk loci in 9p13.3 and 19q13.12, with fine-mapping prioritized variants functionally associated with AQP3 (p = 2.7x10-8) and ARHGAP33 (p = 1.3x10-8), respectively. The meta-analysis of both phases with four European studies stratified by sex from the Host Genetics Initiative confirmed the association of the 3p21.31 and 21q22.11 loci predominantly in males and replicated a recently reported variant in 11p13 (ELF5, p = 4.1x10-8). Six of the COVID-19 HGI discovered loci were replicated and an HGI-based genetic risk score predicted the severity strata in SCOURGE. We also found more SNP-heritability and larger heritability differences by age (<60 or ≥ 60 years) among males than among females. Parallel genome-wide screening of inbreeding depression in SCOURGE also showed an effect of homozygosity in COVID-19 hospitalization and severity and this effect was stronger among older males. In summary, new candidate genes for COVID-19 severity and evidence supporting genetic disparities among sexes are provided

Properties and performance of the prototype instrument for the Pierre Auger Observatory

Copyright © 2003 Elsevier B.V. All rights reserved.Construction of the first stage of the Pierre Auger Observatory has begun. The aim of the Observatory is to collect unprecedented information about cosmic rays above 1018 eV. The first phase of the project, the construction and operation of a prototype system, known as the engineering array, has now been completed. It has allowed all of the sub-systems that will be used in the full instrument to be tested under field conditions. In this paper, the properties and performance of these sub-systems are described and their success illustrated with descriptions of some of the events recorded thus far.Auger Collaboration, ..., J. A. Bellido, ..., R. W. Clay, ..., B. R. Dawson, ..., G. J. Thornton, ..., N. R. Wild, et al.http://www.elsevier.com/wps/find/journaldescription.cws_home/505701/description#descriptio

Correlated Electrons in High Temperature Superconductors

Theoretical ideas and experimental results concerning high temperature superconductors are reviewed. Special emphasis is given to calculations carried out with the help of computers applied to models of strongly correlated electrons proposed to describe the two dimensional ${\rm Cu O_2}$ planes. The review also includes results using several analytical techniques. The one and three band Hubbard models, and the ${\rm t-J}$ model are discussed, and their behavior compared against experiments when available. Among the conclusions of the review, we found that some experimentally observed unusual properties of the cuprates have a natural explanation through Hubbard-like models. In particular abnormal features like the mid-infrared band of the optical conductivity $\sigma(\omega)$, the new states observed in the gap in photoemission experiments, the behavior of the spin correlations with doping, and the presence of phase separation in the copper oxide superconductors may be explained, at least in part, by these models. Finally, the existence of superconductivity in Hubbard-like models is analyzed. Some aspects of the recently proposed ideas to describe the cuprates as having a \dx2y2 superconducting condensate at low temperatures are discussed. Numerical results favor this scenario over others....(continues).Comment: (Submitted to Rev. Mod. Physics