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Biology subjects

Boston, C.

Publications and source records attributed to Boston, C..

2 recordsLinked to original sources

Genomic history and selection in Roman and early medieval Britain

Leading biomedical resources rely on genome variation in Britain1-3, but the historical processes that shaped present-day fine-scale diversity remain debated4-13. Here we sequenced 1039 ancient shotgun genomes from Britain (median 1.4-fold coverage), primarily dating to the first millennium CE. We imputed [~]660 million variants in the UK Biobank14-16 and employed genealogy-based ancestry reconstruction. We found an association between Iron Age consanguinity and matrilineal burial practices17, later disrupted following the Roman Conquest. Despite this societal impact, only 20% of Roman-period individuals carried detectable ancestry from outside Britain. In contrast, from the 6th century CE we detect widespread influx of ancestry in over 70% of individuals in southernAnglo-Saxon Britain, with limited local admixture. We find previously underappreciated heterogeneity, with ancestries associated with Central and Southern Europe rising in prevalence from the 7th century CE. We demonstrate distinct Scandinavian-related ancestry in many Viking-associated contexts, but show that the population-level impact of the Viking Age in Britain was limited. Finally, we detect pre-medieval selection on variants linked with key immunity genes TLR10-TLR1 and IRF8. These results identify population-level and selective processes that shape variation and disease risk in Britain today.

genomics↗

Perfluorooctanoic Acid Induces Liver and Serum Dyslipidemia in Humanized PPARα Mice Fed an American Diet

Per- and polyfluoroalkyl substances (PFAS) are pervasive in the environment resulting in nearly universal detection in people. Human serum PFAS concentrations are strongly associated with increased serum low-density lipoprotein cholesterol (LDL-C), and growing evidence suggests an association with serum triacylglycerides (TG). Here, we tested the hypothesis that perfluorooctanoic acid (PFOA) dysregulates liver and serum triacylglycerides in human peroxisome proliferator activated receptor (hPPAR)-expressing mice fed an American diet. Mice were exposed to PFOA (3.3 mg/l) in drinking water for 6 weeks resulting in a serum concentration of 48 {+/-} 9 g/ml. In male and female hPPAR mice, PFOA increased total liver TG and TG substituted with saturated and monounsaturated fatty acids. Lack of expression of hPPAR alone also increased total liver TG, and PFOA treatment had little effect on liver TG in null mice. In hPPAR mice, PFOA neither significantly increased nor decreased serum TG; however, there was a modest increase in TG associated with very low-density cholesterol particles in both sexes. Across studies, a non-monotonic effect of PFOA on serum TG is evident, with the serum PFOA concentration in this study falling near the "null point" between increasing and decreasing serum TG. Intriguingly, in female PPAR null mice, PFOA significantly increased serum TG, with a similar trend in males. PFOA also modified fatty acid and TG homeostasis-related gene expression in liver, in a hPPAR-dependent manner, but not in adipose. The results reveal the importance of context (serum concentration and genotype) in determining the effect of PFOA on lipid homeostasis.

pharmacology and toxicology↗