Reduced guanidinoacetate in plasma of patients with autosomal dominant Fanconi syndrome due to heterozygous P341L variant and study of organoids towards treatment.

Autosomal dominant Fanconi syndrome due to a variant (GATM-FS), causes accumulation of misfolded arginine-glycine amidinotransferase (AGAT) in proximal renal tubules leading to cellular injury. GATM-FS presents during childhood and progresses to end-stage kidney disease (ESKD) in adults. We study creatine metabolism in two individuals of unrelated families with a known variant and the effect of creatine supplementation in kidney organoids.

Circulating proteins linked to apoptosis processes and fast development of end-stage kidney disease in diabetes.

Many circulating proteins are associated with risk of ESKD, but their source and the biological pathways/disease processes they represent are unclear. Using OLINK proteomics platform, concentrations of 455 proteins were measured in plasma specimens obtained at baseline from 399 individuals with diabetes. Elevated concentrations of 46 circulating proteins were associated (P < 1 × 10-5) with development of ESKD (n = 143) during 7-15 years of follow-up.

Multiomics profiling of mouse polycystic kidney disease progression at a single-cell resolution.

Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary kidney disease and causes significant morbidity, ultimately leading to kidney failure. PKD pathogenesis is characterized by complex and dynamic alterations in multiple cell types during disease progression, hampering a deeper understanding of disease mechanism and the development of therapeutic approaches. Here, we generate a single-nucleus multimodal atlas of an orthologous mouse PKD model at early, mid, and late timepoints, consisting of 125,434 single-nucleus transcriptomic and epigenetic multiomes.

Structural and Spectroscopic Characterization of Supported Sarcoplasmic Reticulum Membranes on Solid Substrates.

Sarcoplasmic reticulum (SR) membranes from rabbit muscle were deposited on silicon substrates and characterized by the combination of spectral ellipsometry (SE), high energy specular X-ray reflectivity (XRR), specular neutron reflectivity (NR), and attenuated total reflection Fourier transform infrared (ATR-FTIR) spectroscopy. Following the optimization of the preparative conditions by SE, the detailed structures in the direction perpendicular to the membrane were probed by XRR. ATR-FTIR data showed strong signals from amide I and amide II bands of the native SR membranes containing a large amount of Ca-ATPase, which could not be achieved by the reconstitution in artificial lipid membranes.