Widespread Allelic Heterogeneity in Complex Traits.

Recent successes in genome-wide association studies (GWASs) make it possible to address important questions about the genetic architecture of complex traits, such as allele frequency and effect size. One lesser-known aspect of complex traits is the extent of allelic heterogeneity (AH) arising from multiple causal variants at a locus. We developed a computational method to infer the probability of AH and applied it to three GWASs and four expression quantitative trait loci (eQTL) datasets. We identified a total of 4,152 loci with strong evidence of AH. The proportion of all loci with identified AH is 4%-23% in eQTLs, 35% in GWASs of high-density lipoprotein (HDL), and 23% in GWASs of schizophrenia. For eQTLs, we observed a strong correlation between sample size and the proportion of loci with AH (R2 = 0.85, p = 2.2 × 10-16), indicating that statistical power prevents identification of AH in other loci. Understanding the extent of AH may guide the development of new methods for fine mapping and association mapping of complex traits.

OxyR2 Modulates OxyR1 Activity and Vibrio cholerae Oxidative Stress Response.

Bacteria have developed capacities to deal with different stresses and adapt to different environmental niches. The human pathogen Vibrio cholerae, the causative agent of the severe diarrheal disease cholera, utilizes the transcriptional regulator OxyR to activate genes related to oxidative stress resistance, including peroxiredoxin PrxA, in response to hydrogen peroxide. In this study, we identified another OxyR homolog in V. cholerae, which we named OxyR2, and we renamed the previous OxyR OxyR1. We found that OxyR2 is required to activate its divergently transcribed gene ahpC, encoding an alkylhydroperoxide reductase, independently of H2O2 A conserved cysteine residue in OxyR2 is critical for this function. Mutation of either oxyR2 or ahpC rendered V. cholerae more resistant to H2O2 RNA sequencing analyses indicated that OxyR1-activated oxidative stress-resistant genes were highly expressed in oxyR2 mutants even in the absence of H2O2 Further genetic analyses suggest that OxyR2-activated AhpC modulates OxyR1 activity by maintaining low intracellular concentrations of H2O2 Furthermore, we showed that ΔoxyR2 and ΔahpC mutants were less fit when anaerobically grown bacteria were exposed to low levels of H2O2 or incubated in seawater. These results suggest that OxyR2 and AhpC play important roles in the V. cholerae oxidative stress response.

Detection of Covid-19 through a Heptanal Biomarker Using Transition Metal Doped Graphene.

A rapid and noninvasive way to monitor the spread of COVID-19 is the detection of SARS-CoV-2 biomarkers from exhaled breath. Heptanal was identified as a key biomarker which was significantly elevated in the breath of SARS-CoV-2 patients. In this study, the adsorption behaviors of heptanal on pristine and transition metal (Pd, Pt, and Ag) doped graphene were studied based on density functional theory. The results indicated that heptanal was weakly adsorbed on pristine graphene with an adsorption energy of -0.015 eV while it was strongly adsorbed on Pd-, Pt-, and Ag-doped graphene with adsorption energies of -0.404, - 0.356, and -0.755 eV, respectively. Also, the electronic properties of Pd-, Pt-, and Ag-doped graphene changed more dramatically after heptanal adsorption than pristine graphene. The recovery times were estimated to be 6.13 × 10-6, 9.57 × 10-7, and 4.83 s for Pd-, Pt-, and Ag-doped graphene, respectively, showing that Pd-, Pt-, and Ag-doped graphene are suitable as reversible sensors. Our results conclude that Pd-, Pt-, and Ag-doped graphene are potential candidates as gas sensors for heptanal detection, and Ag-doped graphene is the most promising one.

Effect of dietary fat and sucrose consumption on cardiac fibrosis in mice and rhesus monkeys.

Calorie restriction (CR) improved health span in 2 longitudinal studies in nonhuman primates (NHPs), yet only the University of Wisconsin (UW) study demonstrated an increase in survival in CR monkeys relative to controls; the National Institute on Aging (NIA) study did not. Here, analysis of left ventricle samples showed that CR did not reduce cardiac fibrosis relative to controls. However, there was a 5.9-fold increase of total fibrosis in UW hearts, compared with NIA hearts. Diet composition was a prominent difference between the studies; therefore, we used the NHP diets to characterize diet-associated molecular and functional changes in the hearts of mice. Consistent with the findings from the NHP samples, mice fed a UW or a modified NIA diet with increased sucrose and fat developed greater cardiac fibrosis compared with mice fed the NIA diet, and transcriptomics analysis revealed diet-induced activation of myocardial oxidative phosphorylation and cardiac muscle contraction pathways.