Glucosylceramide synthase modulation ameliorates murine renal pathologies and promotes macrophage effector function in vitro.

While significant advances have been made in understanding renal pathophysiology, less is known about the role of glycosphingolipid (GSL) metabolism in driving organ dysfunction. Here, we used a small molecule inhibitor of glucosylceramide synthase to modulate GSL levels in three mouse models of distinct renal pathologies: Alport syndrome (Col4a3 KO), polycystic kidney disease (Nek8), and steroid-resistant nephrotic syndrome (Nphs2 cKO). At the tissue level, we identified a core immune-enriched transcriptional signature that was shared across models and enriched in human polycystic kidney disease.

Real-time PCR assays that detect genes for botulinum neurotoxin A-G subtypes.

The role of Real-Time PCR assays for surveillance and rapid screening for pathogens is garnering more and more attention because of its versatility and ease of adoption. The goal of this study was to design, test, and evaluate Real-Time TaqMan PCR assays for the detection of botulinum neurotoxin (/A-G) genes from currently recognized BoNT subtypes. Assays were computationally designed and then laboratory tested for sensitivity and specificity using DNA preparations containing genes from 82 target toxin subtypes, including nine bivalent toxin types; 31 strains representing other clostridial species; and an extensive panel that consisted of DNA from a diverse set of prokaryotic (bacterial) and eukaryotic (fungal, protozoan, plant, and animal) species.

Examining the Relationship Between Workplace Industry and COVID-19 Infection: A Cross-sectional Study of Canada's Largest Rapid Antigen Screening Program.

Objectives: To control virus spread while keeping the economy open, this study aimed to identify individuals at increased risk of COVID-19 transmission in the workplace using rapid antigen screening data.

Methods: Among adult participants in a large Canadian rapid antigen screening program (January 2021-March 2022), we examined screening, personal, and workplace characteristics and conducted logistic regressions, adjusted for COVID-19 wave, screening frequency and location, role, age group, and geography.

Results: Among 145,814 participants across 2707 worksites, 6209 screened positive at least once.

RGS1 Modulates Autophagic and Metabolic Programs and Is a Critical Mediator of Human Regulatory T Cell Function.

Regulatory T cells (Tregs) are critical mediators of immune tolerance and play a diametric role in cancer and autoimmunity. Tumor-infiltrating Tregs are often associated with poor prognosis in solid tumors because their enrichment in the tumor microenvironment contributes to immunosuppression. Conversely, dysregulation in the Treg compartment can disrupt self-tolerance, leading to autoimmunity.

The heme-responsive PrrH sRNA regulates pyochelin gene expression.

is an opportunistic pathogen that requires iron for growth and virulence, yet this nutrient is sequestered by the innate immune system during infection. When iron is limiting, expresses the PrrF1 and PrrF2 small RNAs (sRNAs), which post-transcriptionally repress expression of nonessential iron-containing proteins, thus sparing this nutrient for more critical processes. The genes for the PrrF1 and PrrF2 sRNAs are arranged in tandem on the chromosome, allowing for the transcription of a longer heme-responsive sRNA, termed PrrH.