Human GSK3A peptide

Considering the short life-cycle property, Caenorhabditis elegans is a suitable animal model to evaluate the long-term effects of microgravity stress on organisms. Canonical Wnt/beta-catenin signaling is evolutionarily conserved in various organisms. We here investigated the response of canonical Wnt/beta-catenin signaling pathway to microgravity stress in nematodes. We observed the noticeable response of canonical Wnt/beta-catenin signaling to microgravity stress. In contrast, we did not detect the obvious response of non-canonical Wnt/beta-catenin signaling to microgravity stress. The canonical beta-catenin BAR-1 acted in the intestine to regulate the response to simulated microgravity. Moreover, in the intestine, we identified a signaling cascade of canonical Wnt/beta-catenin signaling pathway in response to simulated microgravity, and this signaling cascade contained Frizzled receptor MIG-1, Disheveled protein DSH-2, GSK3A/GSK-3, and beta-catenin transcriptional factor BAR-1. Our data suggests an important protective response of canonical Wnt/beta-catenin signaling to simulated microgravity in nematodes.

We describe a case of an infant presenting with intractable diarrhea who subsequently developed dilated cardiomyopathy, for whom a diagnosis was not initially achieved despite extensive clinical testing, including panel-based genetic testing. Research-based whole-genome sequences of the proband and both parents were analyzed by the SAVANNA pipeline, a variant prioritization strategy integrating features of variants, genes, and phenotypes, which was implemented using publicly available tools. Although the intestinal morphological abnormalities characteristic of congenital tufting enteropathy (CTE) were not observed in the initial clinical gastrointestinal tract biopsies of the proband, an intronic variant, EPCAM c.556-14A>G, previously identified as pathogenic for CTE, was found in the homozygous state. A newborn cousin of the proband also presenting with intractable diarrhea was found to carry the same homozygous EPCAM variant, and clinical testing revealed intestinal tufting and loss of EPCAM staining. This variant, however, was considered nonexplanatory for the proband's dilated cardiomyopathy, which could be a sequela of the child's condition and/or related to other genetic variants, which include de novo mutations in the genes NEDD4L and GSK3A and a maternally inherited SCN5A variant. This study illustrates three ways in which genomic sequencing can aid in the diagnosis of clinically challenging patients: differential diagnosis despite atypical clinical presentation, distinguishing the possibilities of a syndromic condition versus multiple conditions, and generating hypotheses for novel contributory genes.