Butyrate regulates neutrophil homeostasis and impairs early antimicrobial activity in the lung.

Short-chain fatty acids (SCFAs) are metabolites that are produced after microbial fermentation of dietary fiber and impact cell metabolism and anti-inflammatory pathways both locally in the gut and systemically. In preclinical models, administration of SCFAs, such as butyrate, ameliorates a range of inflammatory disease models including allergic airway inflammation, atopic dermatitis, and influenza infection. Here we report the effect of butyrate on a bacteria-induced acute neutrophil-driven immune response in the airways.

Investigating the association between alcohol intake and male reproductive function: A current meta-analysis.

Background: Alcohol use and alcohol-related health problems are on the rise in developing countries. This meta-analysis was conducted to determine the effects of alcohol consumption on human male reproductive function through semen parameters, antioxidants in semen, sperm DNA fragmentation, and sex hormones.

Methods: Studies regarding the effects of alcohol consumption on male reproductive function were searched on databases.

Analysis of financial challenges faced by graduate students in Canada.

Graduate students are vital to the creation of research and innovation in Canada. The National Graduate Student Finance Survey was launched in 2021 by the Ottawa Science Policy Network to investigate the financial realities of Canadian graduate students. Closing in April 2022, the survey received 1305 responses from graduate students representing various geographical locations, years of study, fields of education, and demographic backgrounds.

A novel anti-inflammatory role links the CARS2 locus to protection from coronary artery disease.

Background And Aims: Genome-wide association studies (GWAS) identified a coronary artery disease (CAD) risk locus on 13.q34 tagged by rs61969072 (T/G). This variant lies in an intergenic region, proximal to ING1, CARKD and CARS2 but its causal relationship to CAD is unknown.

Common Polymorphism That Protects From Cardiovascular Disease Increases Fibronectin Processing and Secretion.

Background: Fibronectin () is an essential regulator of homodynamic processes and tissue remodeling that have been proposed to contribute to atherosclerosis. Moreover, recent large-scale genome-wide association studies (GWAS) have linked common genetic variants within the gene to coronary artery disease risk.

Methods: Public databases were analyzed by 2-Sample Mendelian Randomization.

A Common Polymorphism in the Locus Links miR1908 to Low-Density Lipoprotein Cholesterol Through BMP1.

OBJECTIVE: Leveraging microRNA-Seq data and the 1000 Genomes imputed genotypes, we identified rs174561 as a strong microRNA quantitative trait loci for circulating microRNA-1908-5p with higher miR-1908-5p and reduced LDL (lowdensity lipoprotein)-cholesterol, fasting glucose and A1c concentrations in carriers of the rs-174561-C allele. Here, we have investigated the molecular mechanism(s) linking miR-1908-5p to LDL-C concentrations. APPROACH AND RESULTS: Transfection experiments demonstrate that the presence of the C allele significantly increases miR- 1908-5p abundance relative to the T allele.

NLRC5 promotes transcription of genes and Vγ9Vδ2 T cell-mediated killing.

BTN3A molecules-BTN3A1 in particular-emerged as important mediators of Vγ9Vδ2 T cell activation by phosphoantigens. These metabolites can originate from infections, e.g.

Ultra-deep massively parallel sequencing with unique molecular identifier tagging achieves comparable performance to droplet digital PCR for detection and quantification of circulating tumor DNA from lung cancer patients.

The identification and quantification of actionable mutations are of critical importance for effective genotype-directed therapies, prognosis and drug response monitoring in patients with non-small-cell lung cancer (NSCLC). Although tumor tissue biopsy remains the gold standard for diagnosis of NSCLC, the analysis of circulating tumor DNA (ctDNA) in plasma, known as liquid biopsy, has recently emerged as an alternative and noninvasive approach for exploring tumor genetic constitution. In this study, we developed a protocol for liquid biopsy using ultra-deep massively parallel sequencing (MPS) with unique molecular identifier tagging and evaluated its performance for the identification and quantification of tumor-derived mutations from plasma of patients with advanced NSCLC.

Microbes, metabolites, and the gut-lung axis.

The microbiota plays an essential role in the education, development, and function of the immune system, both locally and systemically. Emerging experimental and epidemiological evidence highlights a crucial cross-talk between the intestinal microbiota and the lungs, termed the 'gut-lung axis'. Changes in the constituents of the gut microbiome, through either diet, disease or medical interventions (such as antibiotics) is linked with altered immune responses and homeostasis in the airways.

Shp-2 Is Dispensable for Establishing T Cell Exhaustion and for PD-1 Signaling In Vivo.

In chronic infection and cancer, T cells acquire a dysfunctional state characterized by the expression of inhibitory receptors. In vitro studies implicated the phosphatase Shp-2 downstream of these receptors, including PD-1. However, whether Shp-2 is responsible in vivo for such dysfunctional responses remains elusive.

NLRC5 shields T lymphocytes from NK-cell-mediated elimination under inflammatory conditions.

NLRC5 is a transcriptional regulator of MHC class I (MHCI), which maintains high MHCI expression particularly in T cells. Recent evidence highlights an important NK-T-cell crosstalk, raising the question on whether NLRC5 specifically modulates this interaction. Here we show that NK cells from Nlrc5-deficient mice exhibit moderate alterations in inhibitory receptor expression and responsiveness.

Generation and characterization of function-blocking anti-ectodysplasin A (EDA) monoclonal antibodies that induce ectodermal dysplasia.

Development of ectodermal appendages, such as hair, teeth, sweat glands, sebaceous glands, and mammary glands, requires the action of the TNF family ligand ectodysplasin A (EDA). Mutations of the X-linked EDA gene cause reduction or absence of many ectodermal appendages and have been identified as a cause of ectodermal dysplasia in humans, mice, dogs, and cattle. We have generated blocking antibodies, raised in Eda-deficient mice, against the conserved, receptor-binding domain of EDA.

Synthesis of a Candida albicans tetrasaccharide spanning the β1,2-mannan phosphodiester α-mannan junction.

The cell wall phosphomannan of Candida species is a complex N-linked glycoprotein with a glycan chain containing predominantly an α-linked mannose backbone with α-mannose branches. A minor β-mannan component is attached to the branches either via a glycosidic bond (acid stable β-mannan) or a phosphodiester bond (acid-labile β-mannan). The α-mannan residues of the cell wall phosphomannan do not afford protective antibody, while the β-mannan portion is a protective antigen and has become an attractive target as the key epitope of a conjugate vaccine.

Electron-deficient dienes. 5. An inverse-electron-demand Diels-Alder approach to 2-substituted 4-methoxyxanthones and 3,4-dimethoxyxanthones.

Several 4-methoxyxanthones and 3,4-dimethoxyxanthones were synthesized in good yield via inverse-electron-demand Diels-Alder (IEDDA) driven domino reactions between a series of electron-deficient chromone-fused dienes with 1-(2,2-dimethoxyvinyl)pyrrolidine or tetramethoxyethene, respectively.