A multi-ancestry genome-wide study incorporating gene-smoking interactions identifies multiple new loci for pulse pressure and mean arterial pressure.

Elevated blood pressure (BP), a leading cause of global morbidity and mortality, is influenced by both genetic and lifestyle factors. Cigarette smoking is one such lifestyle factor. Across five ancestries, we performed a genome-wide gene-smoking interaction study of mean arterial pressure (MAP) and pulse pressure (PP) in 129 913 individuals in stage 1 and follow-up analysis in 480 178 additional individuals in stage 2.

Cerebrospinal fluid neurofilament light chain in multiple sclerosis and its subtypes: a meta-analysis of case-control studies.

Objective: Neurofilament is a biomarker of axonal injury proposed as a useful adjunct in the monitoring of patients with multiple sclerosis (MS). We conducted a systematic review and meta-analysis of case-control studies that have measured neurofilament light chain (NfL) levels in cerebrospinal fluid (CSF) of people with MS (pwMS), in order to determine whether, and to what degree, CSF NfL levels differentiate MS from controls, or the subtypes or stages of MS from each other.

Methods: Guidelines on Preferred Reporting Items for Systematic Reviews and Meta-Analyses were followed.

ER-phagy: shaping up and destressing the endoplasmic reticulum.

The endoplasmic reticulum (ER) network has central roles in metabolism and cellular organization. The ER undergoes dynamic alterations in morphology, molecular composition and functional specification. Remodelling of the network under fluctuating conditions enables the continual performance of ER functions and minimizes stress.

Emerging Principles of Selective ER Autophagy.

The endoplasmic reticulum (ER) is a fundamental organelle in cellular metabolism and signal transduction. It is subject to complex, dynamic sculpting of morphology and composition. Degradation of ER content has an important role to play here.

Epigenome-wide association study of lung function level and its change.

Previous reports link differential DNA methylation (DNAme) to environmental exposures that are associated with lung function. Direct evidence on lung function DNAme is, however, limited. We undertook an agnostic epigenome-wide association study (EWAS) on pre-bronchodilation lung function and its change in adults.

Clinical and molecular characterization of ovarian carcinoma displaying isolated lymph node relapse.

Background: Disease relapse is the primary cause of death from ovarian carcinoma. Isolated lymph node relapse is a rare pattern of ovarian carcinoma recurrence, with a reported median postrelapse survival of 2.5 to 4 years.

Biallelic variants in DNA2 cause microcephalic primordial dwarfism.

Microcephalic primordial dwarfism (MPD) is a group of rare single-gene disorders characterized by the extreme reduction in brain and body size from early development onwards. Proteins encoded by MPD-associated genes play important roles in fundamental cellular processes, notably genome replication and repair. Here we report the identification of four MPD individuals with biallelic variants in DNA2, which encodes an adenosine triphosphate (ATP)-dependent helicase/nuclease involved in DNA replication and repair.

Association of response to TNF inhibitors in rheumatoid arthritis with quantitative trait loci for and CD39.

Objectives: We sought to investigate whether genetic effects on response to TNF inhibitors (TNFi) in rheumatoid arthritis (RA) could be localised by considering known genetic susceptibility loci for relevant traits and to evaluate the usefulness of these genetic loci for stratifying drug response.

Methods: We studied the relation of TNFi response, quantified by change in swollen joint counts ( Δ SJC) and erythrocyte sedimentation rate ( Δ ESR) with locus-specific scores constructed from genome-wide assocation study summary statistics in 2938 genotyped individuals: 37 scores for RA; scores for 19 immune cell traits; scores for expression or methylation of 93 genes with previously reported associations between transcript level and drug response. Multivariate associations were evaluated in penalised regression models by cross-validation.

Mauritian Endemic Medicinal Plant Extracts Induce G2/M Phase Cell Cycle Arrest and Growth Inhibition of Oesophageal Squamous Cell Carcinoma in Vitro.

Terrestrial plants have contributed massively to the development of modern oncologic drugs. Despite the wide acceptance of Mauritian endemic flowering plants in traditional medicine, scientific evidence of their chemotherapeutic potential is lacking. This study aimed to evaluate the tumor cytotoxicity of leaf extracts from five Mauritian endemic medicinal plants, namely Willd (Euphorbiaceae), Bojer (Sapotaceae), Cav.

Mouse ANKRD31 Regulates Spatiotemporal Patterning of Meiotic Recombination Initiation and Ensures Recombination between X and Y Sex Chromosomes.

Orderly segregation of chromosomes during meiosis requires that crossovers form between homologous chromosomes by recombination. Programmed DNA double-strand breaks (DSBs) initiate meiotic recombination. We identify ANKRD31 as a key component of complexes of DSB-promoting proteins that assemble on meiotic chromosome axes.

[Pathological consequences of excess of interferon in vivo].

In this brief review, the authors present a history of the different aspects of the scientific puzzle leading from pioneer animal studies and astute clinical experimental observations to a mature appreciation of the deleterious role of excess of a type I interferon in human pathology.

Pharmacological Inhibition of NFκB Reduces Prostate Cancer Related Osteoclastogenesis In Vitro and Osteolysis Ex Vivo.

NFκB is implicated in cancer and bone remodelling, and we have recently reported that the verified NFκB inhibitor Parthenolide (PTN) reduced osteolysis and skeletal tumour growth in models of metastatic breast cancer. Here, we took advantage of in vitro and ex vivo bone cell and organ cultures to study the effects of PTN on the ability of prostate cancer cells and their derived factors to regulate bone cell activity and osteolysis. PTN inhibited the in vitro growth of a panel of human, mouse and rat prostate cancer cells in a concentration-dependent manner with a varying degree of potency.

Genomic Variants Among Threatened Corals.

Genomic sequence data for non-model organisms are increasingly available requiring the development of efficient and reproducible workflows. Here, we develop the first genomic resources and reproducible workflows for two threatened members of the reef-building coral genus We generated genomic sequence data from multiple samples of the Caribbean (staghorn coral) and (elkhorn coral), and predicted millions of nucleotide variants among these two species and the Pacific A subset of predicted nucleotide variants were verified using restriction length polymorphism assays and proved useful in distinguishing the two Caribbean acroporids and the hybrid they form (""). Nucleotide variants are freely available from the Galaxy server (usegalaxy.

Melissa: Bayesian clustering and imputation of single-cell methylomes.

Measurements of single-cell methylation are revolutionizing our understanding of epigenetic control of gene expression, yet the intrinsic data sparsity limits the scope for quantitative analysis of such data. Here, we introduce Melissa (MEthyLation Inference for Single cell Analysis), a Bayesian hierarchical method to cluster cells based on local methylation patterns, discovering patterns of epigenetic variability between cells. The clustering also acts as an effective regularization for data imputation on unassayed CpG sites, enabling transfer of information between individual cells.

Mitochondrial DNA genomes of five major pest species from the Old and New Worlds (Lepidoptera: Noctuidae).

Five species of noctuid moths, , , , and are major agricultural pests inhabiting various and often overlapping global distributions. Visual identification of these species requires a great deal of expertise and misidentification can have repercussions for pest management and agricultural biosecurity. Here, we report on the complete mitochondrial genomes of and , , and and assembled from high-throughput sequencing data.

Genetic contributions to two special factors of neuroticism are associated with affluence, higher intelligence, better health, and longer life.

Higher scores on the personality trait of neuroticism, the tendency to experience negative emotions, are associated with worse mental and physical health. Studies examining links between neuroticism and health typically operationalize neuroticism by summing the items from a neuroticism scale. However, neuroticism is made up of multiple heterogeneous facets, each contributing to the effect of neuroticism as a whole.

Spotlight on zebrafish: the next wave of translational research.

Five years after the launch of the Disease Models & Mechanisms (DMM) Special Issue on zebrafish as a disease model, the field has progressed significantly. Zebrafish have been used to precisely model human genetic variants, to unpick the mechanisms of metabolic and other diseases, to study infection, inflammation and cancer, and to develop and test new therapeutic approaches. In this Editorial, we highlight recent research published in DMM that uses zebrafish to develop new experimental tools and to provide new insight into disease mechanism and therapy.

Effect of Alendronic Acid on Fracture Healing: A Multicenter Randomized Placebo-Controlled Trial.

There is a concern that bisphosphonates may impair fracture healing because of their inhibitory effects on bone turnover. Here we evaluated the effects of early bisphosphonate therapy on fracture healing and functional outcome following a fracture of the distal radius. The fracture and bisphosphonates (FAB) trial was a double-blind, randomized, placebo-controlled trial involving 15 trauma centers in the United Kingdom.

The influence of X chromosome variants on trait neuroticism.

Autosomal variants have successfully been associated with trait neuroticism in genome-wide analysis of adequately powered samples. But such studies have so far excluded the X chromosome from analysis. Here, we report genetic association analyses of X chromosome and XY pseudoautosomal single nucleotide polymorphisms (SNPs) and trait neuroticism using UK Biobank samples (N = 405,274).

polyadenylation signal variants cause syndromic microphthalmia.

Background: A single variant in (c.471+2T>A), the gene encoding N-acetyltransferase 10, has been associated with Lenz microphthalmia syndrome. In this study, we aimed to identify causative variants in families with syndromic X-linked microphthalmia.

Established and Emerging Immunological Complications of Biological Therapeutics in Multiple Sclerosis.

Biologic immunotherapies have transformed the treatment landscape of multiple sclerosis. Such therapies include recombinant proteins (interferon beta), as well as monoclonal antibodies (natalizumab, alemtuzumab, daclizumab, rituximab and ocrelizumab). Monoclonal antibodies show particular efficacy in the treatment of the inflammatory phase of multiple sclerosis.