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

A consensus protocol for functional connectivity analysis in the rat brain

Task-free functional connectivity in animal models provides an experimental framework to examine connectivity phenomena under controlled conditions and allows for comparisons with data modalities collected under invasive or terminal procedures. Currently, animal acquisitions are performed with varying protocols and analyses that hamper result comparison and integration. Here we introduce StandardRat, a consensus rat functional magnetic resonance imaging acquisition protocol tested across 20 centers. To develop this protocol with optimized acquisition and processing parameters, we initially aggregated 65 functional imaging datasets acquired from rats across 46 centers. We developed a reproducible pipeline for analyzing rat data acquired with diverse protocols and determined experimental and processing parameters associated with the robust detection of functional connectivity across centers. We show that the standardized protocol enhances biologically plausible functional connectivity patterns relative to previous acquisitions. The protocol and processing pipeline described here is openly shared with the neuroimaging community to promote interoperability and cooperation toward tackling the most important challenges in neuroscience

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Towards the Understanding of Important Coconut Endosperm Phenotypes: Is there an Epigenetic Control?

The coconut is a major crop of many tropical countries, with the endosperm being one of its main products. The coconut soft-endosperm variants, the Makapuno and the Lono, are emerging as economically important. This review describes this crop, its salient endosperm phenotypes and the prevailing hypotheses associated with these. We also collate the literature on the Makapuno and provide a comprehensive review of the scarce information on the Lono. We review the current tenets of plant DNA methylation and provide examples of altered phenotypes associated with such methylation changes. We explore how the changes in the methylome affect endosperm development and the tissue culture process. We further cite the epigenetic basis of an altered endosperm phenotype of a closely related species to the coconut, the oil palm. We discuss how such modifications could affect coconut endosperm development, yielding the Makapuno and Lono phenotypes

Putative targets of virus-induced teleost fish homologues of mammalian immune-relevant microribonucleic acids

Background: Microribonucleic acids or microRNAs (miRNAs) are short (18-22 nucleotides) endogenous RNAs that potently regulate the expression of a wide spectrum of genes through the RNA interference mechanism (RNAi). In RNAi, miRNAs repress the translation of target mRNAs or mediate mRNA degradation following interaction with the target 3’-untranslated region (UTR). RNAi has been implicated in the regulation of almost all cellular processes, including host-pathogen interactions. Our previous microarray-based miRNA expression profiling revealed that infection of a salmonid fish with a rhabdovirus induced the expression of several miRNAs in the liver. These miRNAs are homologous to mammalian miRNAs shown to regulate genes involved in immune responses, whereas the roles of these fish miRNAs are yet unclear. Here, we aimed to further investigate the potential interactions of these virus- induced fish miRNAs with mRNAs that may be relevant to host-virus cross-talk. Methodology: To identify potential target mRNAs of 8 of the most highly expressed rhabdovirus-induced miRNAs, we analysed microarray-based mRNA profiles (obtained simultaneously with miRNA expression profiles of the same liver samples). FASTA nucleotide sequences of negatively regulated miRNAs were obtained through NCBI Batch BLAST. The nucleotide sequences were aligned against the Salmon protein database (GCF_000233375.1 version 2) using Local BLASTx (BLAST 2.2.6) to determine identities of presumptive target expressed sequence tags-mRNA. Resulting XML files were further processed for annotation, gene ontology, and inclusive pathways using BLAST2GO 3.1. Additionally, putative targets of the upregulated miRNAs in genomes of salmonid-infecting viruses were predicted using RNA hybrid. Major findings: Analysis of the co-expressed mRNA profiles in the same samples and comparison with miRNA expression data revealed negatively correlated miRNA-mRNA pairs, suggesting miRNA-target relationship. The downregulated mRNAs mapped to more than 80% of the EST-mRNAs in the salmon database. Subsequently, we investigated the potential roles during virus infection of the downregulated mRNAs (and that of their protein products) by analyzing the signaling pathways enriched by the target genes of upregulated miRNAs. Gene-ontology-based annotation and functional/pathway enrichment analysis of inversely correlated mRNAs showed that they are encoded by genes whose protein products were most frequently associated with the cell cycle, immune-relevant pathways, and metabolic pathways known to be altered by virus infections in humans. Finally, analysis of genomes of some salmonid-infecting viruses showed potential targets for rhabdovirus- induced miRNAs, suggesting direct antiviral activities. Conclusions/Perspectives: Our results highlight pathways essential to antiviral defense, besides key miRNAs that modulate these processes. Collectively, our data provide a snapshot of host gene expression dynamics induced by fish rhabdovirus infection and mediated by miRNAs that orchestrate the activities of key regulators of host-virus interactions by their convergent action on multiple target genes involved in these processes. Results will further our understanding of cellular processes that are altered in response to rhabdovirus infection in fish, providing a context for future experimental analyses and functional studies, while miRNA signatures during infection may be used as biomarkers of immune responses in fish and generally, in vertebrates

Legumes as Functional Food for Cardiovascular Disease

Legumes are an essential food source worldwide. Their high-quality proteins, complex carbohydrates, dietary fiber, and relatively low-fat content make these an important functional food. Known to possess a multitude of health benefits, legume consumption is associated with the prevention and treatment of cardiovascular diseases (CVD). Legume crude protein isolates and purified peptides possess many cardiopreventive properties. Here, we review selected economically valued legumes, their taxonomy and distribution, biochemical composition, and their protein components and the mechanism(s) of action associated with cardiovascular health. Most of the legume protein studies had shown upregulation of low-density lipoprotein (LDL) receptor leading to increased binding and uptake, in effect significantly reducing total lipid levels in the blood serum and liver. This is followed by decreased biosynthesis of cholesterol and fatty acids. To understand the relationship of identified genes from legume studies, we performed gene network analysis, pathway, and gene ontology (GO) enrichment. Results showed that the genes were functionally interrelated while enrichment and pathway analysis revealed involvement in lipid transport, fatty acid and triglyceride metabolic processes, and regulatory processes. This review is the first attempt to collate all known mechanisms of action of legume proteins associated with cardiovascular health. This also provides a snapshot of possible targets leading to systems-level approaches to further investigate the cardiometabolic potentials of legumes