Cell state-dependent allelic effects and contextual Mendelian randomization analysis for human brain phenotypes.

Gene expression quantitative trait loci are widely used to infer relationships between genes and central nervous system (CNS) phenotypes; however, the effect of brain disease on these inferences is unclear. Using 2,348,438 single-nuclei profiles from 391 disease-case and control brains, we report 13,939 genes whose expression correlated with genetic variation, of which 16.7-40.

A Simplified Model of Adenine-Induced Chronic Kidney Disease Using SKH1 Mice.

Commonly used adenine-induced chronic kidney disease (CKD) murine models often employ C57BL/6 mice; however, this strain has inherent limitations due to its natural resistance to developing key pathological features of CKD, such as tubulointerstitial fibrosis and inflammation. There have been attempts to overcome these barriers by using multiple concentrations of adenine-supplemented diets or by performing prolonged experiments up to 20 weeks. Here, we demonstrate that SKH1 Elite mice develop clinically relevant CKD phenotypes (e.

snRNA-seq stratifies multiple sclerosis patients into distinct white matter glial responses.

Poor understanding of the cellular and molecular basis of clinical and genetic heterogeneity in progressive multiple sclerosis (MS) has hindered the search for new effective therapies. To address this gap, we analyzed 632,000 single-nucleus RNA sequencing profiles from 156 brain tissue samples of MS and control donors to examine inter- and intra-donor heterogeneity. We found distinct cell type-specific gene expression changes between MS gray and white matter, highlighting clear pathology differences.

Successful Kidney Transplant From a Donor With Marfan Syndrome: A Case Report.

Marfan syndrome, a rare autosomal dominant connective tissue disorder caused by mutations in fibrillin-1, is primarily associated with cardiovascular complications such as aortic aneurysms and dissection. Despite the organ shortage crisis, kidneys from donors with Marfan syndrome are often rejected due to concerns about potential vascular complications. This case report presents the successful transplantation of a kidney from a 47-year-old male donor with Marfan syndrome into a 66-year-old female recipient with end-stage renal disease secondary to diabetic nephropathy.