Whole-Genome Sequencing Of Mesorhizobium huakuii 7653R Provides Molecular Insights into Host Specificity and Symbiosis Island Dynamics

Background Evidence based on genomic sequences is urgently needed to confirm the phylogenetic relationship between Mesorhizobium strain MAFF303099 and M. huakuii. To define underlying causes for the rather striking difference in host specificity between M. huakuii strain 7653R and MAFF303099, several probable determinants also require comparison at the genomic level. An improved understanding of mobile genetic elements that can be integrated into the main chromosomes of Mesorhizobium to form genomic islands would enrich our knowledge of how genome dynamics may contribute to Mesorhizobium evolution in general. Results In this study, we sequenced the complete genome of 7653R and compared it with five other Mesorhizobium genomes. Genomes of 7653R and MAFF303099 were found to share a large set of orthologs and, most importantly, a conserved chromosomal backbone and even larger perfectly conserved synteny blocks. We also identified candidate molecular differences responsible for the different host specificities of these two strains. Finally, we reconstructed an ancestral Mesorhizobium genomic island that has evolved into diverse forms in different Mesorhizobium species. Conclusions Our ortholog and synteny analyses firmly establish MAFF303099 as a strain of M. huakuii. Differences in nodulation factors and secretion systems T3SS, T4SS, and T6SS may be responsible for the unique host specificities of 7653R and MAFF303099 strains. The plasmids of 7653R may have arisen by excision of the original genomic island from the 7653R chromosome

Identification of Rare Copy Number Variants Associated With Pulmonary Atresia With Ventricular Septal Defect

Copy number variants (CNVs) are major variations contributing to the gene heterogeneity of congenital heart diseases (CHD). pulmonary atresia with ventricular septal defect (PA-VSD) is a rare form of cyanotic CHD characterized by complex manifestations and the genetic determinants underlying PA-VSD are still largely unknown. We investigated rare CNVs in a recruited cohort of 100 unrelated patients with PA-VSD, PA-IVS, or TOF and a population-matched control cohort of 100 healthy children using whole-exome sequencing. Comparing rare CNVs in PA-VSD cases and that in PA-IVS or TOF positive controls, we observed twenty-two rare CNVs only in PA-VSD, five rare CNVs only in PA-VSD and TOF as well as thirteen rare CNVs only in PA-VSD and PA-IVS. Six of these CNVs were considered pathogenic or potentially pathogenic to PA-VSD: 16p11.2 del (PPP4C and TBX6), 5q35.3 del (FLT4), 5p13.1 del (RICTOR), 6p21.33 dup (TNXB), 7p15.2 del (HNRNPA2B1), and 19p13.3 dup (FGF22). The gene networks showed that four putative candidate genes for PA-VSD, PPP4C, FLT4, RICTOR, and FGF22 had strong interaction with well-known cardiac genes relevant to heart or blood vessel development. Meanwhile, the analysis of transcriptome array revealed that PPP4C and RICTOR were also significantly expressed in human embryonic heart. In conclusion, three rare novel CNVs were identified only in PA-VSD: 16p11.2 del (PPP4C), 5q35.3 del (FLT4) and 5p13.1 del (RICTOR), implicating novel candidate genes of interest for PA-VSD. Our study provided new insights into understanding for the pathogenesis of PA-VSD and helped elucidate critical genes for PA-VSD

Systematic Review and Meta-Analyses of The Interaction Between HIV Infection And COVID-19: Two Years’ Evidence Summary

Introduction During the COVID-19 pandemic, people living with HIV (PLWH) were considered to be at risk of worse COVID-19 outcomes once infected. However, the existing evidence is inconsistent. This systematic review and meta-analysis aimed to compare the risk of SARS-CoV-2 infection, severe COVID-19 symptoms, and mortality among PLWH and patients without HIV. Method The articles included studies published in PubMed, Medline, Embase, and Cochrane between December 1, 2019, and December 1, 2021. We included the original studies published in English focusing on observational studies assessing the risk of SARS-CoV-2 infection, severe COVID-19 symptoms, and mortality among PLWH. Four independent reviewers extracted data. STrengthening the Reporting of OBservational studies in Epidemiology-Modified (STROBE-M) checklist was used for quality assessment. For the results with heterogeneity I2 >75%, a random-effects model was employed. Otherwise, a fixed-effects model was used. The risk of SARS-CoV-2 infection, severe COVID-19 symptoms, and mortality were compared with and without HIV.ResultsWe included a total of 32 studies and 71,779,737 study samples, of whom 797,564 (1.11%) were PLWH. Compared with COVID-19 patients without HIV infection, PLWH had comparable risk of SARS-CoV-2 infection (adjusted Risk Ratio=1.07, 95% CI: 0.53-2.16, I2 = 96%, study n=6, n=20,199,805) and risk of developing severe COVID-19 symptoms (aRR=1.06, 95% CI: 0.97-1.16, I2 = 75%, n=10, n=2,243,370). PLWH, if infected with SARS-CoV-2, were found to have an increased risk of mortality compared with people without HIV (aRR=1.30, 95% CI: 1.09-1.56, I2 = 76%, study n=16, n=71,032,659). This finding was consistent across different subgroup analyses. Conclusion PLWH are at increased risk of COVID-19 related mortality once infected. The local health system should, on the one hand, strengthen COVID-19 prevention and clinical management among PLWH to avoid infection and, on the other hand, sustain the HIV care continuum for PLWH for HIV management

Loss of p53 in mesenchymal stem cells promotes alteration of bone remodeling through negative regulation of osteoprotegerin.

p53 plays a pivotal role in controlling the differentiation of mesenchymal stem cells (MSCs) by regulating genes involved in cell cycle and early steps of differentiation process. In the context of osteogenic differentiation of MSCs and bone homeostasis, the osteoprotegerin/receptor activator of NF-κB ligand/receptor activator of NF-κB (OPG/RANKL/RANK) axis is a critical signaling pathway. The absence or loss of function of p53 has been implicated in aberrant osteogenic differentiation of MSCs that results in higher bone formation versus erosion, leading to an unbalanced bone remodeling. Here, we show by microCT that mice with p53 deletion systemically or specifically in mesenchymal cells possess significantly higher bone density than their respective littermate controls. There is a negative correlation between p53 and OPG both in vivo by analysis of serum from p53+/+, p53+/-, and p53-/- mice and in vitro by p53 knockdown and ChIP assay in MSCs. Notably, high expression of Opg or its combination with low level of p53 are prominent features in clinical cancer lesion of osteosarcoma and prostate cancer respectively, which correlate with poor survival. Intra-bone marrow injection of prostate cancer cells, together with androgen can suppress p53 expression and enhance local Opg expression, leading to an enhancement of bone density. Our results support the notion that MSCs, as osteoblast progenitor cells and one major component of bone microenvironment, represent a cellular source of OPG, whose amount is regulated by the p53 status. It also highlights a key role for the p53-OPG axis in regulating the cancer associated bone remodeling

Measurement of the top quark forward-backward production asymmetry and the anomalous chromoelectric and chromomagnetic moments in pp collisions at √s = 13 TeV

Abstract The parton-level top quark (t) forward-backward asymmetry and the anomalous chromoelectric (d̂ t) and chromomagnetic (μ̂ t) moments have been measured using LHC pp collisions at a center-of-mass energy of 13 TeV, collected in the CMS detector in a data sample corresponding to an integrated luminosity of 35.9 fb−1. The linearized variable AFB(1) is used to approximate the asymmetry. Candidate t t ¯ events decaying to a muon or electron and jets in final states with low and high Lorentz boosts are selected and reconstructed using a fit of the kinematic distributions of the decay products to those expected for t t ¯ final states. The values found for the parameters are AFB(1)=0.048−0.087+0.095(stat)−0.029+0.020(syst),μ̂t=−0.024−0.009+0.013(stat)−0.011+0.016(syst), and a limit is placed on the magnitude of | d̂ t| < 0.03 at 95% confidence level. [Figure not available: see fulltext.