Genetic Aspects of Implantation Failure

Implantation failure refers to the inability of a fertilized egg, or embryo, to successfully implant itself in the endometrial lining of the uterus, leading to pregnancy loss. The repeated failure of good quality embryo implantation is referred to as recurrent implantation failure (RIF). This can occur for a variety of reasons, including chromosomal abnormalities in the embryo, problems with the endometrium, or issues with the immune system. Factors such as advanced maternal age, obesity, smoking, and certain medical conditions can also increase the risk of implantation failure. While treatment such as in vitro fertilization (IVF) can help to improve the chances of successful implantation, there is currently no definite way to prevent or treat implantation failure.  Patients and healthcare professionals have substantial diagnostic and treatment hurdles as a result of many etiological factors and lack of knowledge about RIF. A number of studies have indicated a correlation between irregular hormone levels, disruptions in angiogenic and immunomodulatory factors, specific genetic polymorphisms, and the prevalence of RIF. Nonetheless, the precise and intricate underlying pathophysiology of RIF remains elusive.  However, many studies are ongoing in this field to understand the underlying causes and to find new ways to help couples achieve pregnancy. This review article extensively explores diverse molecular and genetic facets aimed at enhancing the diagnosis and management of implantation failure

Mucin Biopolymers As Broad-Spectrum Antiviral Agents

Mucus is a porous biopolymer matrix that coats all wet epithelia in the human body and serves as the first line of defense against many pathogenic bacteria and viruses. However, under certain conditions viruses are able to penetrate this infection barrier, which compromises the protective function of native mucus. Here, we find that isolated porcine gastric mucin polymers, key structural components of native mucus, can protect an underlying cell layer from infection by small viruses such as human papillomavirus (HPV), Merkel cell polyomavirus (MCV), or a strain of influenza A virus. Single particle analysis of virus mobility inside the mucin barrier reveals that this shielding effect is in part based on a retardation of virus diffusion inside the biopolymer matrix. Our findings suggest that purified mucins may be used as a broad-range antiviral supplement to personal hygiene products, baby formula or lubricants to support our immune system.National Institutes of Health (U.S.) (grant P30-ES002109)National Institutes of Health (U.S.) (grant P50-GM068763)German Academic Exchange Service (Postdoctoral fellowship

The violent youth of bright and massive cluster galaxies and their maturation over 7 billion years

In this study, we investigate the formation and evolution mechanisms of the brightest cluster galaxies (BCGs) over cosmic time. At high redshift (z ∼ 0.9), we selected BCGs and most massive cluster galaxies (MMCGs) from the Cl1604 supercluster and compared them to low-redshift (z ∼ 0.1) counterparts drawn from the MCXC meta-catalogue, supplemented by Sloan Digital Sky Survey imaging and spectroscopy. We observed striking differences in the morphological, colour, spectral, and stellar mass properties of the BCGs/MMCGs in the two samples. High-redshift BCGs/MMCGs were, in many cases, star-forming, late-type galaxies, with blue broad-band colours, properties largely absent amongst the low-redshift BCGs/MMCGs. The stellar mass of BCGs was found to increase by an average factor of 2.51 ± 0.71 from z ∼ 0.9 to z ∼ 0.1. Through this and other comparisons, we conclude that a combination of major merging (mainly wet or mixed) and in situ star formation are the main mechanisms which build stellar mass in BCGs/MMCGs. The stellar mass growth of the BCGs/MMCGs also appears to grow in lockstep with both the stellar baryonic and total mass of the cluster. Additionally, BCGs/MMCGs were found to grow in size, on average, a factor of ∼3, while their average Sérsic index increased by ∼0.45 from z ∼ 0.9 to z ∼ 0.1, also supporting a scenario involving major merging, though some adiabatic expansion is required. These observational results are compared to both models and simulations to further explore the implications on processes which shape and evolve BCGs/MMCGs over the past ∼7 Gyr

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2–4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

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

Observation of the Rare Decay of the η Meson to Four Muons

A search for the rare η→μ+μ−μ+μ− double-Dalitz decay is performed using a sample of proton-proton collisions, collected by the CMS experiment at the CERN LHC with high-rate muon triggers during 2017 and 2018 and corresponding to an integrated luminosity of 101  fb−1. A signal having a statistical significance well in excess of 5 standard deviations is observed. Using the η→μ+μ− decay as normalization, the branching fraction B(η→μ+μ−μ+μ−)=[5.0±0.8(stat)±0.7(syst)±0.7(B2μ)]×10−9 is measured, where the last term is the uncertainty in the normalization channel branching fraction. This work achieves an improved precision of over 5 orders of magnitude compared to previous results, leading to the first measurement of this branching fraction, which is found to agree with theoretical predictions

Search for new physics in multijet events with at least one photon and large missing transverse momentum in proton-proton collisions at 13 TeV

A search for new physics in final states consisting of at least one photon, multiple jets, and large missing transverse momentum is presented, using proton-proton collision events at a center-of-mass energy of 13 TeV. The data correspond to an integrated luminosity of 137 fb−1, recorded by the CMS experiment at the CERN LHC from 2016 to 2018. The events are divided into mutually exclusive bins characterized by the missing transverse momentum, the number of jets, the number of b-tagged jets, and jets consistent with the presence of hadronically decaying W, Z, or Higgs bosons. The observed data are found to be consistent with the prediction from standard model processes. The results are interpreted in the context of simplified models of pair production of supersymmetric particles via strong and electroweak interactions. Depending on the details of the signal models, gluinos and squarks of masses up to 2.35 and 1.43 TeV, respectively, and electroweakinos of masses up to 1.23 TeV are excluded at 95% confidence level

Search for Scalar Leptoquarks Produced via τ-Lepton-Quark Scattering in pppp Collisions at s=13TeV\sqrt{s}=13 TeV

The first search for scalar leptoquarks produced in τ-lepton–quark collisions is presented. It is based on a set of proton-proton collision data recorded with the CMS detector at the LHC at a center-of-mass energy of 13 TeV corresponding to an integrated luminosity of 138  fb$^{−1}$. The reconstructed final state consists of a jet, significant missing transverse momentum, and a τ lepton reconstructed through its hadronic or leptonic decays. Limits are set on the product of the leptoquark production cross section and branching fraction and interpreted as exclusions in the plane of the leptoquark mass and the leptoquark-τ-quark coupling strength