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

Tetrahydrocannabinol Modulates in Vitro Maturation of Oocytes and Improves the Blastocyst Rates after in Vitro Fertilization

14 Pág.Among the assisted reproductive techniques, the in vitro maturation of oocytes (IVM) is less developed than other techniques, but its implementation would entail a qualitative advance. This technique consists in the extraction of immature oocytes from antral ovarian follicles with the patient under low hormone stimulation or without hormone to mature exogenously in culture media supplemented with different molecules to promote maturation. In this sense, we are interested in the role that cannabinoids could have as IVM promoters because cannabinoid's molecular pathway is similar to the one by which oocyte's meiosis resumption is activated. With the intention of advancing in the possible use of cannabinoids as supplements for the media for in vitro maturation of oocytes, we intend to deepen the study of the function of the phytocannabinoid Δ-9-tetrahydrocannabinol (THC) in the IVM process.This work received financial support from the University of the Basque Country (Grants PPGA18/01 and PPGA19/04) L.T. acknowledges the financial support given by University of the Basque Country (PIF15/149). E.O. has carried out all the experimentation without any public or private financial help. A.P.L.C had the financial support given by Universidad de Antioquia, COLCIENCIAS through the Francisco José de Caldas fellowship 512/2010.Peer reviewe

Impaired spermatogenesis, muscle, and erythrocyte function in U12 intron splicing-defective Zrsr1 mutant mice

The U2AF35-like ZRSR1 has been implicated in the recognition of 3' splice site during spliceosome assembly, but ZRSR1 knockout mice do not show abnormal phenotypes. To analyze ZRSR1 function and its precise role in RNA splicing, we generated ZRSR1 mutant mice containing truncating mutations within its RNA-recognition motif. Homozygous mutant mice exhibited severe defects in erythrocytes, muscle stretch, and spermatogenesis, along with germ cell sloughing and apoptosis, ultimately leading to azoospermia and male sterility. Testis RNA sequencing (RNA-seq) analyses revealed increased intron retention of both U2- and U12-type introns, including U12-type intron events in genes with key functions in spermatogenesis and spermatid development. Affected U2 introns were commonly found flanking U12 introns, suggesting functional cross-talk between the two spliceosomes. The splicing and tissue defects observed in mutant mice attributed to ZRSR1 loss of function suggest a physiological role for this factor in U12 intron splicing.This work was funded by grants AGL2012-39652, BFU2014-55058-P, and AGL2015-66145 from the Spanish Ministry of Economy and Competitiveness and Japan Grants-in-Aid for Scientific Research 26830124 from the Ministry of Education, Culture, Sports, Science and Technology. K.H. was supported by Young Scientists Development Program, Research Center for Advanced Science and Technology at the University of Tokyo (funded by FUJIFILM Corporation). Work in J.V.'s lab was also supported by the European Research Council (ERC AdG - GA670146 - MASCP)

First measurement of the Z→μ+μ−Z\rightarrow \mu^+ \mu^- angular coefficients in the forward region of pppp collisions at s=13\sqrt{s}=13 TeV

The first study of the angular distribution of $\mu^+ \mu^-$ pairs produced in the forward rapidity region via the Drell-Yan reaction $pp \rightarrow \gamma^{*}/Z +X \rightarrow l^+ l^- + X$ is presented, using data collected with the LHCb detector at a centre-of-mass energy of 13TeV, corresponding to an integrated luminosity of 5.1 $\rm{fb}^{-1}$. The coefficients of the five leading terms in the angular distribution are determined as a function of the dimuon transverse momentum and rapidity. The results are compared to various theoretical predictions of the $Z$-boson production mechanism and can also be used to probe transverse-momentum-dependent parton distributions within the proton

Precision measurement of forward ZZ boson production in proton-proton collisions at s=13\sqrt{s} = 13 TeV

A precision measurement of the $Z$ boson production cross-section at $\sqrt{s} = 13$ TeV in the forward region is presented, using $pp$ collision data collected by the LHCb detector, corresponding to an integrated luminosity of 5.1 fb$^{-1}$. The production cross-section is measured using $Z\rightarrow\mu^+\mu^-$ events within the fiducial region defined as pseudorapidity $2.020$ GeV/$c$ for both muons and dimuon invariant mass $60<M_{\mu\mu}<120$ GeV/$c^2$. The integrated cross-section is determined to be \begin{equation*} \sigma(Z\rightarrow\mu^+\mu^-) = 195.3 \pm 0.2 \pm 1.5 \pm 3.9~pb, \end{equation*} where the first uncertainty is statistical, the second is systematic, and the third is due to the luminosity determination. The measured results are in agreement with theoretical predictions, including a prediction at next-to-next-to-leading order in perturbative quantum chromodynamics and a prediction with resummation

Measurement of the charm mixing parameter yCP−yCPKπy_{CP} - y_{CP}^{K\pi} using two-body D0D^0 meson decays

International audienceA measurement of the ratios of the effective decay widths of D0→π-π+ and D0→K-K+ decays over that of D0→K-π+ decays is performed with the LHCb experiment using proton–proton collisions at a centre-of-mass energy of 13 TeV, corresponding to an integrated luminosity of 6  fb-1. These observables give access to the charm mixing parameters yCPππ-yCPKπ and yCPKK-yCPKπ, and are measured as yCPππ-yCPKπ=(6.57±0.53±0.16)×10-3, yCPKK-yCPKπ=(7.08±0.30±0.14)×10-3, where the first uncertainties are statistical and the second systematic. The combination of the two measurements is yCP-yCPKπ=(6.96±0.26±0.13)×10-3, which is four times more precise than the previous world average

Search for the rare hadronic decay Bs0→ppˉB_s^0\to p \bar{p}

A search for the rare hadronic decay Bs0→pp¯ is performed using proton-proton collision data recorded by the LHCb experiment at a center-of-mass energy of 13 TeV, corresponding to an integrated luminosity of 6  fb-1. No evidence of the decay is found and an upper limit on its branching fraction is set at B(Bs0→pp¯)&lt;4.4(5.1)×10-9 at 90% (95%) confidence level; this is currently the world’s best upper limit. The decay mode B0→pp¯ is measured with very large significance, confirming the first observation by the LHCb experiment in 2017. The branching fraction is determined to be B(B0→pp¯)=(1.27±0.15±0.05±0.04)×10-8, where the first uncertainty is statistical, the second is systematic and the third is due to the external branching fraction of the normalization channel B0→K+π-. The combination of the two LHCb measurements of the B0→pp¯ branching fraction yields B(B0→pp¯)=(1.27±0.13±0.05±0.03)×10-8.A search for the rare hadronic decay $B_s^0\to p \bar{p}$ is performed using proton-proton collision data recorded by the LHCb experiment at a center-of-mass energy of 13 TeV, corresponding to an integrated luminosity of 6 fb$^{-1}$. No evidence of the decay is found and an upper limit on its branching fraction is set at ${\cal B}(B_s^0\to p \bar{p}) < 4.4~(5.1) \times 10^{-9}$ at 90% (95%) confidence level; this is currently the world's best upper limit. The decay mode $B^0\to p \bar{p}$ is measured with very large significance, confirming the first observation by the LHCb experiment in 2017. The branching fraction is determined to be ${\cal B}(B^0\to p \bar{p}) = \rm (1.27 \pm 0.15 \pm 0.05 \pm 0.04) \times 10^{-8}$, where the first uncertainty is statistical, the second is systematic and the third is due to the external branching fraction of the normalization channel $B^0\to K^+\pi^-$. The combination of the two LHCb measurements of the $B^0\to p \bar{p}$ branching fraction yields ${\cal B}(B^0\to p \bar{p}) = \rm (1.27 \pm 0.13 \pm 0.05 \pm 0.03) \times 10^{-8}$

First measurement of the Z→μ+μ−Z\rightarrow \mu^+ \mu^- angular coefficients in the forward region of pppp collisions at s=13\sqrt{s}=13 TeV

The first study of the angular distribution of $\mu^+ \mu^-$ pairs produced in the forward rapidity region via the Drell-Yan reaction $pp \rightarrow \gamma^{*}/Z +X \rightarrow l^+ l^- + X$ is presented, using data collected with the LHCb detector at a centre-of-mass energy of 13TeV, corresponding to an integrated luminosity of 5.1 $\rm{fb}^{-1}$. The coefficients of the five leading terms in the angular distribution are determined as a function of the dimuon transverse momentum and rapidity. The results are compared to various theoretical predictions of the $Z$-boson production mechanism and can also be used to probe transverse-momentum-dependent parton distributions within the proton

Measurement of the charm mixing parameter yCP−yCPKπy_{CP} - y_{CP}^{K\pi} using two-body D0D^0 meson decays

A measurement of the ratios of the effective decay widths of $D^0 \to \pi^-\pi^+$ and $D^0 \to K^-K^+$ decays over that of $D^0 \to K^-\pi^+$ decays is performed with the LHCb experiment using proton-proton collisions at a centre-of-mass energy of $13 \, \mathrm{TeV}$, corresponding to an integrated luminosity of $6 \, \mathrm{fb^{-1}}$. These observables give access to the charm mixing parameters $y_{CP}^{\pi\pi} - y_{CP}^{K\pi}$ and $y_{CP}^{KK} - y_{CP}^{K\pi}$, and are measured as $y_{CP}^{\pi\pi} - y_{CP}^{K\pi} = (6.57 \pm 0.53 \pm 0.16) \times 10^{-3}$, $y_{CP}^{KK} - y_{CP}^{K\pi} = (7.08 \pm 0.30 \pm 0.14) \times 10^{-3}$, where the first uncertainties are statistical and the second systematic. The combination of the two measurements is $y_{CP} - y_{CP}^{K\pi} = (6.96 \pm 0.26 \pm 0.13) \times 10^{-3}$, which is four times more precise than the previous world average

Measurement of the charm mixing parameter yCP−yCPKπy_{CP} - y_{CP}^{K\pi} using two-body D0D^0 meson decays

A measurement of the ratios of the effective decay widths of $D^0 \to \pi^-\pi^+$ and $D^0 \to K^-K^+$ decays over that of $D^0 \to K^-\pi^+$ decays is performed with the LHCb experiment using proton-proton collisions at a centre-of-mass energy of $13 \, \mathrm{TeV}$, corresponding to an integrated luminosity of $6 \, \mathrm{fb^{-1}}$. These observables give access to the charm mixing parameters $y_{CP}^{\pi\pi} - y_{CP}^{K\pi}$ and $y_{CP}^{KK} - y_{CP}^{K\pi}$, and are measured as $y_{CP}^{\pi\pi} - y_{CP}^{K\pi} = (6.57 \pm 0.53 \pm 0.16) \times 10^{-3}$, $y_{CP}^{KK} - y_{CP}^{K\pi} = (7.08 \pm 0.30 \pm 0.14) \times 10^{-3}$, where the first uncertainties are statistical and the second systematic. The combination of the two measurements is $y_{CP} - y_{CP}^{K\pi} = (6.96 \pm 0.26 \pm 0.13) \times 10^{-3}$, which is four times more precise than the previous world average