Antigen Presenting Cells Link the Female Genital Tract Microbiome to Mucosal Inflammation, With Hormonal Contraception as an Additional Modulator of Inflammatory Signatures.

The microbiome of the female genital tract (FGT) is closely linked to reproductive health outcomes. Diverse, anaerobe-dominated communities with low abundance are associated with a number of adverse reproductive outcomes, such as preterm birth, cervical dysplasia, and sexually transmitted infections (STIs), including HIV. Vaginal dysbiosis is associated with local mucosal inflammation, which likely serves as a biological mediator of poor reproductive outcomes.

Fecal Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-Cov-2) RNA Is Associated With Decreased Coronavirus Disease 2019 (COVID-19) Survival.

The clinical significance of severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) RNA in stool remains uncertain. We found that extrapulmonary dissemination of infection to the gastrointestinal tract, assessed by the presence of SARS-CoV-2 RNA in stool, is associated with decreased coronavirus disease 2019 (COVID-19) survival. Measurement of SARS-CoV-2 RNA in stool may have utility for clinical risk assessment.

Rapid Discovery and Characterization of Synthetic Neutralizing Antibodies against Anthrax Edema Toxin.

Anthrax, a lethal, weaponizable disease caused by Bacillus anthracis, acts through exotoxins that are primary mediators of systemic toxicity and also targets for neutralization by passive immunotherapy. The ease of engineering B. anthracis strains resistant to established therapy and the historic use of the microbe in bioterrorism present a compelling test case for platforms that permit the rapid and modular development of neutralizing agents.

Ensemble cryoEM elucidates the mechanism of insulin capture and degradation by human insulin degrading enzyme.

Insulin degrading enzyme (IDE) plays key roles in degrading peptides vital in type two diabetes, Alzheimer's, inflammation, and other human diseases. However, the process through which IDE recognizes peptides that tend to form amyloid fibrils remained unsolved. We used cryoEM to understand both the apo- and insulin-bound dimeric IDE states, revealing that IDE displays a large opening between the homologous ~55 kDa N- and C-terminal halves to allow selective substrate capture based on size and charge complementarity.

The Influence of Cervicovaginal Microbiota on Mucosal Immunity and Prophylaxis in the Battle against HIV.

Purpose Of Review: Young women in sub-Saharan Africa bear a disproportionate burden of the global HIV epidemic. In this review, we examine how cervicovaginal microbiota modulate structural and immune defenses in the female genital tract and influence HIV susceptibility.

Recent Findings: Highly diverse, anaerobic cervicovaginal microbiota prevalent in sub-Saharan African women increase HIV acquisition risk by over fourfold.

Lactobacillus-Deficient Cervicovaginal Bacterial Communities Are Associated with Increased HIV Acquisition in Young South African Women.

Elevated inflammation in the female genital tract is associated with increased HIV risk. Cervicovaginal bacteria modulate genital inflammation; however, their role in HIV susceptibility has not been elucidated. In a prospective cohort of young, healthy South African women, we found that individuals with diverse genital bacterial communities dominated by anaerobes other than Gardnerella were at over 4-fold higher risk of acquiring HIV and had increased numbers of activated mucosal CD4 T cells compared to those with Lactobacillus crispatus-dominant communities.