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

Multi-functional silica microdot arrays by inkjet printing for biosensor applications

International audienceSilica-based microarrays for molecular recognition are realized using a piezoelectric drop-on-demand inkjet printer. In an evaporation induced self-assembly route, a silica sol containing (3-azidopropyl)triethoxysilane is used as ink to print azido-functionalized mesoporous silica microdots arrays clickable with various alkyno-peptides, in accordance with the Huisgen 1,3 dipolar cycloaddition commonly called "click reaction". In a similar route, a second ink is formulated integrating an alkyne silylated precursor. By using a multi-printhead system, a bi-material of intercrossed azido and alkyno-functionalized network can be built. The successive reactions with clickable peptides lead to the array multi-functionalization. The success of the click chemistry, EISA and inkjet printing combination highly depends on the ink formulation, which is adjusted in regards to the viscosity and surface tension in the appropriate range for inkjet printing

Silica-based nanosensors fabricated combining top-down and bottom-up processes through the use of an Ink-jet Printing technology

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Réseaux multifonctionnels élaborés par impression jet d'encre et chimie " click " pour des applications de type biocapteurs

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Interests of inkjet printing technology for the fabrication of highly sensitive and selective biosensors

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