Zhang, L. N. | bioRxiv Science

bioRxiv2024

The Role of Sex in Atherosclerotic Inflammation and Lipid-Handling Dysfunction

Residual risk of cardiovascular events remains despite treatments that effectively lower cholesterol levels and hypertension, suggesting that there must be more variables to consider in atherosclerosis treatment. Several studies have suggested sex1,2,3 and inflammation4,5 as important variables. However, a cross-cohort analysis of sex and risk factors like inflammation and lipid-handling dysfunction is needed to strengthen their connection to atherosclerosis. By using blood transcriptomic profiles of 391 male and female participants, this study revealed that inflammation and lipid-handling dysfunction have sex-specific roles in atherosclerosis. Transcriptomics of 391 human blood samples with varying degrees of atherosclerosis were used to identify sex-specific changes in immune response and lipid-handling in circulating blood cells. Preliminary analyses of both FPKM and normalized counts datasets showed that inflammatory pathway activation and enrichment increased as atherosclerotic disease severity increased across all sexes. Analysis of sex-specific differentially expressed genes (DEGs) using IPAs Canonical Pathways showed that severely impacted females had more enriched inflammatory pathways than severely impacted males. Further cross-cohort analysis of sex-specific inflammation and lipid-handling dysfunction was performed using AtheroSpectrum, a single-sample macrophage annotation tool. AtheroSpectrum confirmed that inflammation was more critical to female atherogenesis and revealed that lipid-handling dysfunction was more critical to male atherogenesis. Our study underscored the importance of inflammation and sex as variables to consider in atherosclerosis treatment, suggesting that treatment should target inflammation and consider sex. Our findings may be used for generating a model to predict atherosclerosis risk based on key DEGs, pathways, sex, and other clinical parameters when available.

bioinformatics↗

bioRxiv2022

Delimiting the cryptic diversity and host preferences of Sycophila parasitoid wasps associated with oak galls using phylogenomic data

Cryptic species diversity is a major challenge for the species-rich community of parasitoids attacking oak gall wasps due to a high degree of sexual dimorphism, morphological plasticity, small size, and poorly known biology. As such, we know very little about the number of species present, nor the evolutionary forces responsible for generating this diversity. One hypothesis is that trait diversity in the gall wasps, including the morphology of the galls they induce, has evolved in response to selection imposed by the parasitoid community, with reciprocal selection driving diversification of the parasitoids. Using a rare, continental-scale data set of Sycophila parasitoid wasps reared from 44 species of cynipid galls from 18 species of oak across the US, we combined mitochondrial DNA barcodes, Ultraconserved Elements (UCEs), morphological, and natural history data to delimit putative species. Using these results, we generate the first large-scale assessment of ecological specialization and host association in this species-rich group, with implications for evolutionary ecology and biocontrol. We find most Sycophila target specific subsets of available cynipid host galls with similar morphologies, and generally attack larger galls. Our results suggest that parasitoid wasps such as Sycophila have adaptations allowing them to exploit particular host trait combinations, while hosts with contrasting traits are resistant to attack. These findings support the tritrophic niche concept for the structuring of plant-herbivore-parasitoid communities.

evolutionary biology↗