25 research outputs found
Mutations in the Desmoglein 4 Gene Are Associated with Monilethrix-like Congenital Hypotrichosis
The gene encoding human desmoglein 4 (DSG4) was recently cloned, and a mutation in this gene has been reported in several consanguineous Pakistani families affected with localized autosomal recessive hypotrichosis (LAH). In addition, various mutations in the Dsg4 gene have been identified in animal models of hypotrichosis that share a characteristic phenotype called “lanceolate hair”. To date, the features of the hair-shaft anomaly in patients with LAH have not been well described. We report a Japanese patient affected with congenital hypotrichosis that was originally diagnosed as monilethrix because she had a hair-shaft abnormality that resembled moniliform hair. However, no mutations were found in the type II hair keratin genes, hHb1, hHb3, and hHb6, whose mutations cause monilethrix. Instead, we identified novel compound heterozygous mutations in the DSG4 gene of our patient. On the maternal allele is a novel S192P transition within the extracellular cadherin II domain of DSG4; on the paternal allele is a novel 2039insT mutation leading to the generation of unstable transcripts. Here we present the observation that mutations in the DSG4 gene can cause monilethrix-like congenital hypotrichosis. Based on our findings, we propose that LAH and monilethrix could overlap
nsPEFs induce the ISR via ROS-mediated HRI activation
The integrated stress response (ISR) is one of the most important cytoprotective mechanisms and is integrated by phosphorylation of the α subunit of eukaryotic translation initiation factor 2 (eIF2α). Four eIF2α kinases, heme-regulated inhibitor (HRI), double-stranded RNA-dependent protein kinase (PKR), PKR-like endoplasmic reticulum kinase (PERK), and general control nonderepressible 2 (GCN2), are activated in response to several stress conditions. We previously reported that nanosecond pulsed electric fields (nsPEFs) are a potential therapeutic tool for ISR activation. In this study, we examined which eIF2α kinase is activated by nsPEF treatment. To assess the responsible eIF2α kinase, we used previously established eIF2α kinase quadruple knockout (4KO) and single eIF2α kinase-rescued 4KO mouse embryonic fibroblast (MEF) cells. nsPEFs 70 ns in duration with 30 kV/cm electric fields caused eIF2α phosphorylation in wild-type (WT) MEF cells. On the other hand, nsPEF-induced eIF2α phosphorylation was completely abolished in 4KO MEF cells and was recovered by HRI overexpression. CM-H2DCFDA staining showed that nsPEFs generated reactive oxygen species (ROS), which activated HRI. nsPEF-induced eIF2α phosphorylation was blocked by treatment with the ROS scavenger N-acetyl-L-cysteine (NAC). Our results indicate that the eIF2α kinase HRI is responsible for nsPEF-induced ISR activation and is activated by nsPEF-generated ROS
A Kerato-Epithelin (βig-h3) Mutation in Lattice Corneal Dystrophy Type IIIA
This report covers phase 2 of the IWMI-Tata Water Policy Research Program (ITP) for the period 2006-2010. The major areas of action: Research focusing on water sector issues concerning underprivileged communities and backward regions in the country; Idea-incubation for livelihoods enhancement efforts using water as a central input, supporting the Trust in their water sector partnerships; Dissemination and raising public awareness; Widening the network of research partners; Policy influencing
Fundamental Investigation of Streamer Discharges in Coaxial Reactor for NO <italic>x</italic>
Size Polymorphisms in the Human Ultrahigh Sulfur Hair Keratin-Associated Protein 4, KAP4, Gene Family
A novel three-carbon annelation method for pyridine derivatives
Cyclopentane ring annelation methods for 2-pyridone derivatives are provided by cyclobutane ring expansion of 1, 2-dihydrocyclobuta [c] pyridin-3 (4H)-ones having an appropriate function at the l-position. Since the latter compounds are readily accessible from 4-alkoxy-2-pyridones via our two-step procedure (Kaneko-Naito method), the methods seem to have wide applicability for the synthesis of cyclopenta [c] pyridines