Akt phosphorylation was assessed by Western blotting.\n\nRESULTS. The limbal epithelial cells of FIH-1 null mice had an increase in glycogen levels as well as increased c-kit ligand mRNA compared with wild-type controls. Consistent with a FIH-1/c-kit association, the diminished Akt signaling observed in FIH-1-overexpressing HCEKs could be restored by the addition of c-kit ligand. Interestingly, Akt signaling and glycogen content of the corneal epithelium were significantly decreased in c-kit mutant mice.\n\nCONCLUSIONS. c-Kit signaling has been shown to affect

glucose metabolism via the Akt/GSK-3 beta pathway. An inverse relationship between FIH-1 and c-kit signaling pathways accounts, in part, for differences in glycogen content between corneal GDC-0068 cell line and limbal epithelial cells.”
“Canonical animal microRNAs (miRNAs) are similar to 22-nt regulatory RNAs generated by stepwise cleavage of primary hairpin transcripts by the Drosha and Dicer RNase III enzymes. We performed a genetic VS-4718 mouse screen using an miRNA-repressed reporter in the Drosophila eye and recovered the first reported alleles of fly drosha, an allelic series of its dsRBD partner pasha, and novel alleles of dicer-1. Analysis

of drosha mutants provided direct confirmation that mirtrons are independent of this nuclease, as inferred earlier from pasha knockouts. We further used these mutants to demonstrate in vivo cross-regulation of Drosha and Pasha in the intact animal, confirming remarkable conservation of a homeostatic mechanism that aligns

their respective levels. Although the loss of core miRNA pathway components is universally lethal in animals, we unexpectedly recovered hypomorphic alleles that gave adult escapers with overtly normal development. However, the mutant photoreceptor neurons exhibited reduced synaptic transmission, without accompanying defects in neuronal development or maintenance. These findings indicate that synaptic function is especially sensitive to optimal miRNA pathway function. These allelic series of miRNA pathway mutants see more should find broad usage in studies of miRNA biogenesis and biology in the Drosophila system.”
“BACKGROUND Understanding sudden cardiac death in the young may inform prevention strategies.\n\nOBJECTIVE To determine the scope and nature of sudden death in a geographically defined population.\n\nMETHODS We performed a retrospective population-based cohort study in Ontario, Canada, of all sudden cardiac death cases involving persons aged 2-40 years identified from the 2008 comprehensive Coroner database. Of 1741 Coroner’s cases, 376 were considered potential sudden cardiac death cases and underwent review.\n\nRESULTS There were 174 cases of adjudicated sudden cardiac death from a population of 6,602,680 persons aged 2-40 years. Structural heart disease was present in 126 cases (72%), 78% of which was unrecognized.