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yang, d.

Publications and source records attributed to yang, d..

2 recordsLinked to original sources

Genetic association between posterior parietal cortex and intelligence

The identification of intelligence-associated loci raises questions for functional association of brain regions and for different intelligence concepts of either a general capability or discrete abilities. By generating single-nucleus transcriptomic atlas of mouse posterior parietal cortex (PPC), which is implicated in quantification behavior, we find that human intelligence-associated gene homologs are significantly enriched in certain specific neurons within the PPC. We also find 73% of the human intelligence gene homologs are highly enriched in PPC. In addition to PPC, several regions at different locations, not cortex next to PPC, are also significantly associated with intelligence genes. The separate locations of these cortex regions and their regional-specific expressed intelligence genes raise the possibility for discrete intelligence capabilities. Animal behavior analysis reveals that mutations for two top intelligence-associated genes with specific expression in either PPC or entorhinal cortex (ENT) affect quantification or learning and memory, respectively. Finally, five patients with PPC resection in the left hemisphere also display quantification defects, but not other cognitive abilities. Together, our studies provide the first genetic and functional evidence for the involvement of PPC in intelligence. Our data also support the model of multiple intelligence over a general capability for intelligence.

genetics↗

IDOL deficiency inhibits cholesterol-rich diet-induced atherosclerosis in rabbits

BACKGROUNDThe E3 ubiquitin ligase IDOL (Inducible Degrader of the LDL-Receptor) contributes to regulation of cholesterol metabolism through degradation of LDLR, VLDLR and ApoER2. Human genetic studies support the hypothesis that IDOL could serve as a target for the treatment of dyslipidemia. However, species-specific differences in overall lipid metabolism and IDOL regulation require new preclinical models to realize its therapeutic potential. We leveraged the advantages afforded by the rabbit model to address those limitations and generated a novel rabbit IDOL knockout, which we characterized in the context of atherosclerosis. METHODSIDOL-/- rabbits were generated by CRISPR/Cas9 technology. IDOL-/- and wildtype littermates, on standard (SD) and atherogenic high-cholesterol diets (HCDs) were compared through assessment of lipid and lipoprotein profiles, triglyceride clearance, lipoprotein lipase (LPL) activity, liver pathology, atherosclerosis development, and fecal cholesterol, with bile acid contents assessed by mass spectrometry. ResultsHepatic IDOL expression was increased in response to hypercholesterolemia and hypertriglyceridemia induced by HCD. On SD, loss of IDOL increased LDLR stability with reduced total cholesterol in plasma. On HCD, IDOL-/- rabbits showed simultaneous and remarkable reduction in hypercholesterolemia and hypertriglyceridemia associated with enhanced lipid clearance and LPL activity as well as increased bile acid excretion in feces. IDOL-/- rabbits presented markedly reduced HCD-induced atherosclerosis in the aorta and left coronary artery, without enhanced liver steatosis. CONCLUSIONSLoss of IDOL in rabbits recapitulates human genetic findings, thus setting the stage to accelerate preclinical studies towards development of strategies targeting IDOL for the treatment of atherosclerotic cardiovascular disease.

physiology↗