Oxygen-induced stress reveals context-specific gene regulatory effects in human brain organoids.

The interaction between genetic variants and environmental stressors is key to understanding the mechanisms underlying neurological diseases. In this study, we used human brain organoids to explore how varying oxygen levels expose context-dependent gene regulatory effects. By subjecting a genetically diverse panel of 21 brain organoids to hypoxic and hyperoxic conditions, we identified thousands of gene regulatory changes that are undetectable under baseline conditions, with 1,745 trait-associated genes showing regulatory effects only in response to oxygen stress.

Vagal TRPV1 sensory neurons regulate myeloid cell dynamics and protect against influenza virus infection.

Influenza viruses are a major global cause of morbidity and mortality. Vagal TRPV1 nociceptive sensory neurons, which innervate the airways, are known to mediate defenses against harmful agents. However, their function in lung antiviral defenses remains unclear.

Where Are the Disease-Associated eQTLs?

Most disease-associated variants, although located in putatively regulatory regions, do not have detectable effects on gene expression. One explanation could be that we have not examined gene expression in the cell types or conditions that are most relevant for disease. Even large-scale efforts to study gene expression across tissues are limited to human samples obtained opportunistically or postmortem, mostly from adults.

An Airway Protection Program Revealed by Sweeping Genetic Control of Vagal Afferents.

Sensory neurons initiate defensive reflexes that ensure airway integrity. Dysfunction of laryngeal neurons is life-threatening, causing pulmonary aspiration, dysphagia, and choking, yet relevant sensory pathways remain poorly understood. Here, we discover rare throat-innervating neurons (∼100 neurons/mouse) that guard the airways against assault.

Neural Sensing of Organ Volume.

Many internal organs change volume periodically. For example, the stomach accommodates ingested food and drink, the bladder stores urine, the heart fills with blood, and the lungs expand with every breath. Specialized peripheral sensory neurons function as mechanoreceptors that detect tissue stretch to infer changes in organ volume and then relay this information to the brain.

Genetic Determinants of Penicillin Tolerance in Vibrio cholerae.

Many bacteria are resistant to killing (tolerant) by typically bactericidal antibiotics due to their ability to counteract drug-induced cell damage. , the cholera agent, displays an unusually high tolerance to diverse inhibitors of cell wall synthesis. Exposure to these agents, which in other bacteria leads to lysis and death, results in a breakdown of the cell wall and subsequent sphere formation in Spheres readily recover to rod-shaped cells upon antibiotic removal, but the mechanisms mediating the recovery process are not well characterized.

Author Correction: Nociceptor sensory neurons suppress neutrophil and γδ T cell responses in bacterial lung infections and lethal pneumonia.

In the version of this article initially published, the line graph showing TNF-α levels in Fig. 2d was inadvertently duplicated. A graph of IL-6 levels should be shown in place of the duplication.

Nociceptor sensory neurons suppress neutrophil and γδ T cell responses in bacterial lung infections and lethal pneumonia.

Lung-innervating nociceptor sensory neurons detect noxious or harmful stimuli and consequently protect organisms by mediating coughing, pain, and bronchoconstriction. However, the role of sensory neurons in pulmonary host defense is unclear. Here, we found that TRPV1 nociceptors suppressed protective immunity against lethal Staphylococcus aureus pneumonia.

Sensory Neurons that Detect Stretch and Nutrients in the Digestive System.

Neural inputs from internal organs are essential for normal autonomic function. The vagus nerve is a key body-brain connection that monitors the digestive, cardiovascular, and respiratory systems. Within the gastrointestinal tract, vagal sensory neurons detect gut hormones and organ distension.

A Transposon Screen Identifies Genetic Determinants of Vibrio cholerae Resistance to High-Molecular-Weight Antibiotics.

Gram-negative bacteria are notoriously resistant to a variety of high-molecular-weight antibiotics due to the limited permeability of their outer membrane (OM). The basis of OM barrier function and the genetic factors required for its maintenance remain incompletely understood. Here, we employed transposon insertion sequencing to identify genes required for Vibrio cholerae resistance to vancomycin and bacitracin, antibiotics that are thought to be too large to efficiently penetrate the OM.

Predictive MRI correlates of lesser metatarsophalangeal joint plantar plate tear.

Purpose: To identify correlated signs on non-enhanced MRI that might improve diagnostic detection of plantar plate (PP) tear.

Materials And Methods: We performed an IRB-approved, HIPAA-compliant retrospective analysis of 100 non-contrast MRI (50 PP tear, 50 controls). All were anonymized, randomized, and reviewed; 20 were duplicated to assess consistency.

Fatty acids linked to cardiovascular mortality are associated with risk factors.

Background: Although saturated fatty acids (FAs) have been linked to cardiovascular mortality, it is not clear whether this outcome is attributable solely to their effects on low-density lipoprotein cholesterol (LDL-C) or whether other risk factors are also associated with FAs. The Western Alaskan Native population, with its rapidly changing lifestyles, shift in diet from unsaturated to saturated fatty acids and dramatic increase in cardiovascular disease (CVD), presents an opportunity to elucidate any associations between specific FAs and known CVD risk factors.

Objective: We tested the hypothesis that the specific FAs previously identified as related to CVD mortality are also associated with individual CVD risk factors.

Vagal Sensory Neuron Subtypes that Differentially Control Breathing.

Breathing is essential for survival and under precise neural control. The vagus nerve is a major conduit between lung and brain required for normal respiration. Here, we identify two populations of mouse vagus nerve afferents (P2ry1, Npy2r), each a few hundred neurons, that exert powerful and opposing effects on breathing.