Biology subjects

Jiang, C. S.

Publications and source records attributed to Jiang, C. S..

4 recordsLinked to original sources

bioRxiv2024

Next Generation Neuropeptide Y Receptor Small Molecule Agonists Inhibit Mosquito Biting Behavior

Female Aedes aegypti mosquitoes can spread disease-causing pathogens when they bite humans to obtain blood nutrients required for egg production. Following a complete blood meal, host-seeking is suppressed until eggs are laid. Neuropeptide Y-like Receptor 7 (NPYLR7) plays a role in endogenous host-seeking suppression and previous work identified small molecule NPYLR7 agonists that suppress host-seeking and blood feeding when fed to mosquitoes at high micromolar doses. Using structure activity relationship analysis and structure-guided design we synthesized 128 compounds with similarity to known NPYLR7 agonists. Although in vitro potency (EC50) was not strictly predictive of in vivo effect, we identified 3 compounds that suppressed blood feeding from a live host when fed to mosquitoes at a 1 M dose, a 100-fold improvement over the original reference compound. Exogenous activation of NPYLR7 represents an innovative vector control strategy to block mosquito biting behavior and prevent mosquito/human host interactions that lead to pathogen transmission.

pharmacology and toxicology↗

bioRxiv2022

Sex differences in inter-individual gene expression variability across human tissues

Understanding phenotypic sex differences has long been a goal of biology from both a medical and evolutionary perspective. Although much attention has been paid to mean differences in phenotype between the sexes, little is known about sex differences in phenotypic variability. To gain insight into sex differences in inter-individual variability at the molecular level, we analyzed RNA-seq data from 43 tissues from the Genotype-Tissue Expression project (GTEx). Within each tissue, we identified genes that show sex differences in gene expression variability. We found that these sex-differentially variable (SDV) genes are associated with various important biological functions, including sex hormone response, immune response, and other signaling pathways. By analyzing single-cell RNA sequencing data collected from breast epithelial cells, we found that genes with sex differences in gene expression variability in breast tissue tend to be expressed in a cell-type-specific manner. We looked for an association between SDV expression and Graves disease, a well-known heavily female-biased disease, and found a significant enrichment of Graves associated genes among genes with higher variability in females in thyroid tissue. This suggests a possible role for SDV expression in the context of sex-biased disease. We then examined the evolutionary constraints acting on genes with sex differences in variability and found that they exhibit evidence of increased selective constraint. Through analysis of sex-biased eQTL data, we found evidence that SDV expression may have a genetic basis. Finally, we propose a simple evolutionary model for the emergence of sex-differentially variable expression from sex-specific constraints.

evolutionary biology↗

bioRxiv2022

Differential mosquito attraction to humans is associated with skin-derived carboxylic acid levels

Female Aedes aegypti mosquitoes feed on human blood, which they use to develop their eggs. It has been widely noted that some people are more attractive to mosquitoes than others, but the mechanistic basis of this phenomenon is poorly understood. Here we tested mosquito attraction to skin odor collected from human subjects and identified people who are exceptionally attractive or unattractive to mosquitoes. Notably, these preferences were stable over several years, indicating consistent longitudinal differences in skin odor between subjects. We carried out gas chromatography/quadrupole time of flight-mass spectrometry to analyze the chemical composition of human skin odor in these subjects and discovered that highly attractive people produce significantly increased levels of carboxylic acids. Mosquitoes could reliably distinguish a highly attractive human from their weakly attractive counterparts unless we substantially diluted the odor of the "mosquito magnet." This is consistent with the hypothesis that odor concentration is a major driver of differential attraction, rather than the less-favored skin odor blend containing repellent odors, although these are not mutually- exclusive. Mosquitoes detect carboxylic acids with a large family of odor-gated ion channels encoded by the Ionotropic Receptor gene superfamily. Mutant mosquitoes lacking any of the Ionotropic Receptor (IR) co-receptors Ir8a, Ir25a, and Ir76b, were severely impaired in attraction to human scent but retained the ability to differentiate highly and weakly attractive people. The link between elevated carboxylic acids in "mosquito-magnet" human skin odor and phenotypes of genetic mutations in carboxylic acid receptors suggests that such compounds contribute to differential mosquito attraction. Understanding why some humans are more attractive than others provides insights into what skin odorants are most important to the mosquito and could inform the development of more effective repellents.

neuroscience↗

bioRxiv2020

Brown Adipose Tissue is Associated with Improved Cardiometabolic Health and Regulates Blood Pressure

White fat stores excess energy, while brown and beige fat dissipate energy as heat1. These thermogenic adipose tissues markedly improve glucose and lipid homeostasis in mouse models, though the extent to which brown adipose tissue (BAT) influences metabolic and cardiovascular disease in humans is unclear2, 3, 4. Here, we categorized 139,224 18F-FDG PET/CT scans from 53,475 patients by presence or absence of BAT and used propensity score matching to assemble a study cohort. Individuals with BAT showed lower prevalences of cardiometabolic diseases. Additionally, BAT independently correlated with lower odds of type II diabetes, coronary artery disease and congestive heart failure. These findings were supported by improved glucose, triglyceride and high-density lipoprotein values. The effects of BAT were more pronounced in overweight and obesity, indicating that BAT can offset the deleterious effects of obesity. Strikingly, we also found lower rates of hypertension among patients with BAT. Studies in a mouse model with genetic ablation of beige fat demonstrated elevated blood pressure due to increased sensitivity to angiotensin II in peripheral resistance arteries. In addition to highlighting a role for BAT in promoting overall cardiometabolic health, this study reveals a new link between thermogenic adipose tissue and blood pressure regulation.

physiology↗