Progressive hearing loss in mice carrying a mutation in Usp53

UNLABELLED: Disordered protein ubiquitination has been linked to neurodegenerative disease, yet its role in inner ear homeostasis and hearing loss is essentially unknown. Here we show that progressive hearing loss in the ethylnitrosourea-generated mambo mouse line is caused by a mutation in Usp53, a member of the deubiquitinating enzyme family. USP53 contains a catalytically inactive ubiquitin-specific protease domain and is expressed in cochlear hair cells and a subset of supporting cells. Although hair cell differentiation is unaffected in mambo mice, outer hair cells degenerate rapidly after the first postnatal week. USP53 colocalizes and interacts with the tight junction scaffolding proteins TJP1 and TJP2 in polarized epithelial cells, suggesting that USP53 is part of the tight junction complex. The barrier properties of tight junctions of the stria vascularis appeared intact in a biotin tracer assay, but the endocochlear potential is reduced in adult mambo mice. Hair cell degeneration in mambo mice precedes endocochlear potential decline and is rescued in cochlear organotypic cultures in low potassium milieu, indicating that hair cell loss is triggered by extracellular factors. Remarkably, heterozygous mambo mice show increased susceptibility to noise injury at high frequencies. We conclude that USP53 is a novel tight junction-associated protein that is essential for the survival of auditory hair cells and normal hearing in mice, possibly by modulating the barrier properties and mechanical stability of tight junctions. SIGNIFICANCE STATEMENT: Hereditary hearing loss is extremely prevalent in the human population, but many genes linked to hearing loss remain to be discovered. Forward genetics screens in mice have facilitated the identification of genes involved in sensory perception and provided valuable animal models for hearing loss in humans. This involves introducing random mutations in mice, screening the mice for hearing defects, and mapping the causative mutation. Here, we have identified a mutation in the Usp53 gene that causes progressive hearing loss in the mambo mouse line. We demonstrate that USP53 is a catalytically inactive deubiquitinating enzyme and a novel component of tight junctions that is necessary for sensory hair cell survival and inner ear homeostasis

Complete genome sequence of Desulfurispirillum indicum strain S5T

Desulfurispirillum indicum strain S5T is a strictly anaerobic bacterium isolated from river sediment in Chennai, India. D. indicum belongs to the deep branching phylum of Chrysiogenetes, which currently only includes three other cultured species. Strain S5T is the type strain of the species and it is capable of growth using selenate, selenite, arsenate, nitrate or nitrite as terminal electron acceptors. The 2,928,377 bp genome encodes 2,619 proteins and 49 RNA genes, and the information gained from its sequence will be relevant to the elucidation of microbially-mediated transformations of arsenic and selenium, in addition to deepening our knowledge of the underrepresented phylum of Chrysiogenetes

Parkin-Mediated Mitophagy in Mutant hAPP Neurons and Alzheimer’s Disease Patient Brains

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Caminibacter mediatlanticus sp. nov., a thermophilic, hemolithoautotrophic, nitrate-ammonifying bacterium isolated from a deep-sea hydrothermal vent on the Mid-Atlantic Ridge

) and pH 4?5 and 7?5 (optimum pH 5?5). Generation time under optimal conditions was 50 min. Growth occurred under chemolithoautotrophic conditions with H 2 as the energy source and CO 2 as the carbon source. Nitrate or sulfur was used as the electron acceptor, with resulting production of ammonium and hydrogen sulfide, respectively. Oxygen, thiosulfate, sulfite, selenate and arsenate were not used as electron acceptors. Growth was inhibited by the presence of acetate, lactate, formate and peptone. The G+C content of the genomic DNA was 25?6 mol%. Phylogenetic analysis of the 16S rRNA gene sequence indicated that this organism is closely related to Caminibacter hydrogeniphilus and Caminibacter profundus (95?9 and 96?3 % similarity, respectively). On the basis of phylogenetic, physiological and genetic considerations, it is proposed that the organism represents a novel species within the genus Caminibacter, Caminibacter mediatlanticus sp. nov. The type strain is TB-2

Sulfurovum riftiae sp. nov., a mesophilic, thiosulfate-oxidizing, nitrate-reducing chemolithoautotrophic epsilonproteobacterium isolated from the tube of the deep-sea hydrothermal vent polychaete Riftia pachyptila

An anaerobic, nitrate-reducing, sulfur- and thiosulfate-oxidizing bacterium, designated strain 1812E T , was isolated from the vent polychaete Riftia pachyptila, which was collected from a deep-sea hydrothermal vent on the East Pacific Rise. Cells were Gram-stain-negative rods, measuring approximately 1.05±0.11 μm by 0.40±0.05 μm. Strain 1812E T grew at 25–45 C (optimum 35 C), with 1.5–4.0 % (w/v) NaCl (optimum 3.0 %) and at pH 5.0–8.0 (optimum pH 6.0). The generation time under optimal conditions was 3 h. Strain 1812E T was an anaerobic chemolithotroph that grew with either sulfur or thiosulfate as the energy source and carbon dioxide as the sole carbon source. Nitrate was used as a sole terminal electron acceptor. The predominant fatty acids were C 16 : 1 !7c, C 18 : 1 !7c and C 16 : 0 . The major polar lipids were phosphatidylethanolamine, diphosphatidylglycerol and phosphatidylglycerol. The major respiratory quinone was menaquinone MK-6 and the G+C content of the genomic DNA was 47.4 mol%. Phylogenetic analysis of the 16S rRNA gene of strain 1812E T showed that the isolate belonged to the Epsilonproteobacteria, and its closest relatives were Sulfurovum lithotrophicum 42BKT T and Sulfurovum aggregans Monchim 33 T (98.3 and 95.7 % sequence similarity, respectively). DNA–DNA relatedness between strain 1812E T and the type strain of S. lithotrophicum was 29.7 %, demonstrating that the two strains are not members of the same species. Based on the phylogenetic, molecular, chemotaxonomic and physiological evidence, strain 1812E T represents a novel species within the genus Sulfurovum, for which the name Sulfurovum riftiae sp. nov. is proposed. The type strain is 1812E T (=DSM 101780 T =JCM 30810 T )