Genome-wide association meta-analyses and fine-mapping elucidate pathways influencing albuminuria

Increased levels of the urinary albumin-to-creatinine ratio (UACR) are associated with higher risk of kidney disease progression and cardiovascular events, but underlying mechanisms are incompletely understood. Here, we conduct trans-ethnic (n = 564,257) and European-ancestry specific meta-analyses of genome-wide association studies of UACR, including ancestry- and diabetes-specific analyses, and identify 68 UACR-associated loci. Genetic correlation analyses and risk score associations in an independent electronic medical records database (n = 192,868) reveal connections with proteinuria, hyperlipidemia, gout, and hypertension. Fine-mapping and trans-Omics analyses with gene expression in 47 tissues and plasma protein levels implicate genes potentially operating through differential expression in kidney (including TGFB1, MUC1, PRKCI, and OAF), and allow coupling of UACR associations to altered plasma OAF concentrations. Knockdown of OAF and PRKCI orthologs in Drosophila nephrocytes reduces albumin endocytosis. Silencing fly PRKCI further impairs slit diaphragm formation. These results generate a priority list of genes and pathways for translational research to reduce albuminuria

Hyperfine interactions at 181 Hf(→ 181 Ta) impurities implanted in Er 2O 3 and Gd 2O 3: structural and electronic dependence of the EFG in bixbyite sesquioxides

PACS. 61.72.Ww Doping and impurity implantation in other materials – 76.80.+y Mössbauer effect; other gamma-ray spectroscopy – 71.70.Jp Nuclear states and interactions,

Centralskolan för konstflit - berättelse över skolans verksamhet under dess 72:dra arbetsår 1946-1947

Sisältää tietoja mm. opettajista ja opiskelijoista, lahjoituksista, opiskelijoiden määristä, opetusohjelmasta, valmistuneista opiskelijoista, myönnetyistä avustuksista ja palkinnoista sekä näytteitä oppilastöistä