Search results for "genetics"
showing 10 items of 12494 documents
Variants of human CLDN9 cause mild to profound hearing loss
2021
Hereditary deafness is clinically and genetically heterogeneous. We investigated deafness segregating as a recessive trait in two families. Audiological examinations revealed an asymmetric mild to profound hearing loss with childhood or adolescent onset. Exome sequencing of probands identified a homozygous c.475G>A;p.(Glu159Lys) variant of CLDN9 (NM_020982.4) in one family and a homozygous c.370_372dupATC;p.(Ile124dup) CLDN9 variant in an affected individual of a second family. Claudin 9 (CLDN9) is an integral membrane protein and constituent of epithelial bicellular tight junctions that form semi-permeable, paracellular barriers between inner ear perilymphatic and endolymphatic compartment…
An extended catalogue of ncRNAs in Streptomyces coelicolor reporting abundant tmRNA, RNase-P RNA and RNA fragments derived from pre-ribosomal RNA lea…
2022
Streptomyces coelicolor is a model organism for studying streptomycetes. This genus possesses relevant medical and economical roles, because it produces many biologically active metabolites of pharmaceutical interest, including the majority of commercialized antibiotics. In this bioinformatic study, the transcriptome of S. coelicolor has been analyzed to identify novel RNA species and quantify the expression of both annotated and novel transcripts in solid and liquid growth medium cultures at different times. The major characteristics disclosed in this study are: (i) the diffuse antisense transcription; (ii) the great abundance of transfer-messenger RNAs (tmRNA); (iii) the abundance of rnpB…
Single-cell analysis of population context advances RNAi screening at multiple levels
2012
Isogenic cells in culture show strong variability, which arises from dynamic adaptations to the microenvironment of individual cells. Here we study the influence of the cell population context, which determines a single cell's microenvironment, in image‐based RNAi screens. We developed a comprehensive computational approach that employs Bayesian and multivariate methods at the single‐cell level. We applied these methods to 45 RNA interference screens of various sizes, including 7 druggable genome and 2 genome‐wide screens, analysing 17 different mammalian virus infections and four related cell physiological processes. Analysing cell‐based screens at this depth reveals widespread RNAi‐induce…
Evolutionary advantage conferred by an eukaryote-to-eukaryote gene transfer event in wine yeasts
2015
Although an increasing number of horizontal gene transfers have been reported in eukaryotes, experimental evidence for their adaptive value is lacking. Here, we report the recent transfer of a 158-kb genomic region between Torulaspora microellipsoides and Saccharomyces cerevisiae wine yeasts or closely related strains. This genomic region has undergone several rearrangements in S. cerevisiae strains, including gene loss and gene conversion between two tandemly duplicated FOT genes encoding oligopeptide transporters. We show that FOT genes confer a strong competitive advantage during grape must fermentation by increasing the number and diversity of oligopeptides that yeast can utilize as a s…
Double copies of blaKPC-3::Tn4401a on an IncX3 plasmid in Klebsiella pneumoniae successful clone ST512 from Italy
2015
ABSTRACT A carbapenem-resistant sequence type 512 (ST512) Klebsiella pneumoniae carbapenemase 3 (KPC-3)-producing K. pneumoniae strain showing a novel variant plasmid content was isolated in Palermo, Italy, in 2014. ST512 is a worldwide successful clone associated with the spread of bla KPC genes located on the IncFIIk pKpQIL plasmid. In our ST512 strain, the bla KPC-3 gene was unusually located on an IncX3 plasmid, whose complete sequence was determined. Two copies of bla KPC-3 ::Tn 4401a caused by intramolecular transposition events were detected in the plasmid.
The prolyl-isomerase PIN1 is essential for nuclear Lamin-B structure and function and protects heterochromatin under mechanical stress.
2021
Summary: Chromatin organization plays a crucial role in tissue homeostasis. Heterochromatin relaxation and consequent unscheduled mobilization of transposable elements (TEs) are emerging as key contributors of aging and aging-related pathologies, including Alzheimer’s disease (AD) and cancer. However, the mechanisms governing heterochromatin maintenance or its relaxation in pathological conditions remain poorly understood. Here we show that PIN1, the only phosphorylation-specific cis/trans prolyl isomerase, whose loss is associated with premature aging and AD, is essential to preserve heterochromatin. We demonstrate that this PIN1 function is conserved from Drosophila to humans and prevents…
A Novel Pathophysiological Mechanism Contributing to Trigeminal Neuralgia
2016
Trigeminal neuralgia (TN) is a form of neuropathic pain that affects the fifth cranial nerve, the most widely distributed nerve in the head. Although TN has been associated with a variety of pathological conditions, neurovascular compression on the trigeminal nerve, as it exits the brain stem, is the most frequent reported cause. This compression provides a progressive demyelination of the nerve and a subsequent aberrant neural transmission. Although several studies have clarified some physiopathological mechanisms underlying TN, the molecular basis remains vague. Very recently the substitution of methionine 136 by valine (MET126Val) in sodium channel Nav1.6 in a case study of typical TN ha…
Identification of mycorrhiza-regulated genes with arbuscule development-related expression profile
2004
Suppressive subtractive hybridisation was applied to the analysis of late stage arbuscular mycorrhizal development in pea. 96 cDNA clones were amplified and 81, which carried fragments more than 200 nt in size, were sequence analysed. Among 67 unique fragments, 10 showed no homology and 10 were similar to sequences with unknown function. RNA accumulation of the corresponding 67 genes was analysed by hybridisation of macro-arrays. The cDNAs used as probes were derived from roots of wild type and late mutant pea genotypes, inoculated or not with the AM fungus Glomus mosseae. After calibration, a more than 2.5-fold mycorrhiza-induced RNA accumulation was detected in two independent experiments…
In-depth characterization of denitrifier communities across different soil ecosystems in the tundra
2022
Abstract Background In contrast to earlier assumptions, there is now mounting evidence for the role of tundra soils as important sources of the greenhouse gas nitrous oxide (N2O). However, the microorganisms involved in the cycling of N2O in this system remain largely uncharacterized. Since tundra soils are variable sources and sinks of N2O, we aimed at investigating differences in community structure across different soil ecosystems in the tundra. Results We analysed 1.4 Tb of metagenomic data from soils in northern Finland covering a range of ecosystems from dry upland soils to water-logged fens and obtained 796 manually binned and curated metagenome-assembled genomes (MAGs). We then sear…
Experimental Evolution Reveals a Genetic Basis for Membrane-Associated Virus Release
2021
Many animal viruses replicate and are released from cells in close association to membranes. However, whether this is a passive process or is controlled by the virus remains poorly understood. Importantly, the genetic basis and evolvability of membrane-associated viral shedding have not been investigated. To address this, we performed a directed evolution experiment using coxsackievirus B3, a model enterovirus, in which we repeatedly selected the free-virion or the fast-sedimenting membrane-associated viral subpopulations. The virus responded to this selection regime by reproducibly fixing a series of mutations that altered the extent of membrane-associated viral shedding, as revealed by fu…