Search results for "Generation"
showing 10 items of 3050 documents
Targeted next-generation sequencing of deafness genes in hearing-impaired individuals uncovers informative mutations
2014
Purpose: Targeted next-generation sequencing provides a remarkable opportunity to identify variants in known disease genes, particularly in extremely heterogeneous disorders such as nonsyndromic hearing loss. The present study attempts to shed light on the complexity of hearing impairment. Methods: Using one of two next-generation sequencing panels containing either 80 or 129 deafness genes, we screened 30 individuals with nonsyndromic hearing loss (from 23 unrelated families) and analyzed 9 normal-hearing controls. Results: Overall, we found an average of 3.7 variants (in 80 genes) with deleterious prediction outcome, including a number of novel variants, in individuals with nonsyndromic h…
Regulation of X-Chromosome-Linked Inhibitor of Apoptosis Protein in Kainic Acid-Induced Neuronal Death in the Rat Hippocampus
2001
XIAP (X-chromosome-linked inhibitor of apoptosis protein) is an antiapoptotic protein which inhibits the activity of caspases and suppresses cell death. However, little is known about the presence and function of XIAP in the nervous system. Here we report that XIAP mRNA is expressed in developing and adult rat brain. Using a specific antibody, we observed XIAP-immunoreactive cells in different brain regions, among others, in the hippocampus and cerebral cortex. Kainic acid, which induces delayed cell death of specific neurons, increased the levels of XIAP in the CA3 region of hippocampus. XIAP was, however, largely absent in cells undergoing cell death, as shown by TUNEL labeling and staini…
Remodeling of alveolar septa after murine pneumonectomy
2015
In most mammals, removing one lung (pneumonectomy) results in the compensatory growth of the remaining lung. In mice, stereological observations have demonstrated an increase in the number of mature alveoli; however, anatomic evidence of the early phases of alveolar growth has remained elusive. To identify changes in the lung microstructure associated with neoalveolarization, we used tissue histology, electron microscopy, and synchrotron imaging to examine the configuration of the alveolar duct after murine pneumonectomy. Systematic histological examination of the cardiac lobe demonstrated no change in the relative frequency of dihedral angle components (Ends, Bends, and Junctions) ( P >…
Induction of RAGE Shedding by Activation of G Protein-Coupled Receptors
2011
The multiligand Receptor for Advanced Glycation End products (RAGE) is involved in various pathophysiological processes, including diabetic inflammatory conditions and Alzheimers disease. Full-length RAGE, a cell surface-located type I membrane protein, can proteolytically be converted by metalloproteinases ADAM10 and MMP9 into a soluble RAGE form. Moreover, administration of recombinant soluble RAGE suppresses activation of cell surface-located RAGE by trapping RAGE ligands. Therefore stimulation of RAGE shedding might have a therapeutic value regarding inflammatory diseases. We aimed to investigate whether RAGE shedding is inducible via ligand-induced activation of G protein-coupled recep…
A comparative evaluation of NB30, NB54 and PTC124 in translational read-through efficacy for treatment of an USH1C nonsense mutation
2012
Translational read-through-inducing drugs (TRIDs) promote read-through of nonsense mutations, placing them in the spotlight of current gene-based therapeutic research. Here, we compare for the first time the relative efficacies of new-generation aminoglycosides NB30, NB54 and the chemical compound PTC124 on retinal toxicity and read-through efficacy of a nonsense mutation in the USH1C gene, which encodes the scaffold protein harmonin. This mutation causes the human Usher syndrome, the most common form of inherited deaf-blindness. We quantify read-through efficacy of the TRIDs in cell culture and show the restoration of harmonin function. We do not observe significant differences in the read…
Retinal ganglion cell loss is accompanied by antibody depositions and increased levels of microglia after immunization with retinal antigens.
2012
BackgroundAntibodies against retinal and optic nerve antigens are detectable in glaucoma patients. Recent studies using a model of experimental autoimmune glaucoma demonstrated that immunization with certain ocular antigens causes an immun-mediated retinal ganglion cell loss in rats.Methodology/principal findingsRats immunized with a retinal ganglion cell layer homogenate (RGA) had a reduced retinal ganglion cell density on retinal flatmounts (p = 0.007) and a lower number of Brn3(+) retinal ganglion cells (p = 0.0001) after six weeks. The autoreactive antibody development against retina and optic nerve was examined throughout the study. The levels of autoreactive antibodies continuously in…
Autoreactive Antibodies and Loss of Retinal Ganglion Cells in Rats Induced by Immunization with Ocular Antigens
2011
PURPOSE In an experimental autoimmune animal model, retinal ganglion cell (RGC) loss was induced through immunization with glaucoma-related antigens. The target of this study was to investigate the pathomechanism behind this decline and the serum antibody reactivity against ocular and neuronal tissues after immunization with glaucoma- and non-glaucoma-associated antigens. METHODS Rats immunized with optic nerve antigen homogenate (ONA) or keratin (KER) were compared to control rats (CO). Intraocular pressure (IOP) was measured, and the fundi were examined regularly. Four weeks afterward, cells were counted in retinal flat mounts. Retina, optic nerve, and brain sections from healthy animals …
Retinas of the Diurnal RodentArvicanthis ansorgeiAre Highly Resistant to Experimentally Induced Stress and Degeneration
2011
International audience; PURPOSE. Environmentally induced stress plays a significant role in retinal degeneration and blindness both in animals and in humans. Among such sources of stress, phototoxicity is well studied and has been shown to lead to photoreceptor-specific loss in a number of species. However, the vast majority of studies have been conducted in nocturnal, albino rod-dominant rat and mouse strains, and the pertinence of such findings to human pathology and cone loss is debatable. The authors examined retinal vulnerability to damage in the diurnal murid rodent Arvicanthis ansorgei, a pigmented species with a large number of cones. METHODS. The authors used established protocols …
Retinal oxidation, apoptosis and age- and sex-differences in the mnd mutant mouse, a model of neuronal ceroid lipofuscinosis
2004
Retinal degeneration is an early and progressive event in many forms of neuronal ceroid lipofuscinoses (NCLs), a heterogeneous group of neurodegenerative disorders with unknown pathogenesis. We here used the mutant motor neuron degeneration (mnd) mouse, a late-infantile NCL variant, to investigate the retinal oxidative state and apoptotic cell death as a function of age and sex. Total superoxide dismutase (SOD) activities and thiobarbituric acid-reactive substance (TBARS) levels revealed progressive increases in retinal oxyradicals and lipid peroxides of mnd mice of both sexes. Female mnd retinas showed a higher oxidation rate and consistently exhibited the 4-hydroxy-2-nonenal (4-HNE)-adduc…
Mutation ofPOC1Bin a Severe Syndromic Retinal Ciliopathy
2014
We describe a consanguineous Iraqi family with Leber congenital amaurosis (LCA), Joubert syndrome (JBTS), and polycystic kidney disease (PKD). Targeted next-generation sequencing for excluding mutations in known LCA and JBTS genes, homozygosity mapping, and whole-exome sequencing identified a homozygous missense variant, c.317G>C (p.Arg106Pro), in POC1B, a gene essential for ciliogenesis, basal body, and centrosome integrity. In silico modeling suggested a requirement of p.Arg106 for the formation of the third WD40 repeat and a protein interaction interface. In human and mouse retina, POC1B localized to the basal body and centriole adjacent to the connecting cilium of photoreceptors and in …