Search results for "muta"
showing 10 items of 6895 documents
Chance and necessity in the genome evolution of endosymbiotic bacteria of insects.
2017
An open question in evolutionary biology is how does the selection–drift balance determine the fates of biological interactions. We searched for signatures of selection and drift in genomes of five endosymbiotic bacterial groups known to evolve under strong genetic drift. Although most genes in endosymbiotic bacteria showed evidence of relaxed purifying selection, many genes in these bacteria exhibited stronger selective constraints than their orthologs in free-living bacterial relatives. Remarkably, most of these highly constrained genes had no role in the host–symbiont interactions but were involved in either buffering the deleterious consequences of drift or other host-unrelated function…
DNA Damage Signaling Instructs Polyploid Macrophage Fate in Granulomas.
2018
Granulomas are immune cell aggregates formed in response to persistent inflammatory stimuli. Granuloma macrophage subsets are diverse and carry varying copy numbers of their genomic information. The molecular programs that control the differentiation of such macrophage populations in response to a chronic stimulus, though critical for disease outcome, have not been defined. Here, we delineate a macrophage differentiation pathway by which a persistent Toll-like receptor (TLR) 2 signal instructs polyploid macrophage fate by inducing replication stress and activating the DNA damage response. Polyploid granuloma-resident macrophages formed via modified cell divisions and mitotic defects and not…
Dysregulation of DNA methylation induced by past arsenic treatment causes persistent genomic instability in mammalian cells
2015
The mechanisms by which arsenic-induced genomic instability is initiated and maintained are poorly understood. To investigate potential epigenetic mechanisms, in this study we evaluated global DNA methylation levels in V79 cells and human HaCaT keratinocytes at several time points during expanded growth of cell cultures following removal of arsenite exposures. We have found altered genomic methylation patterns that persisted up to 40 cell generations in HaCaT cells after the treatments were withdrawn. Moreover, mRNA expression levels were evaluated by RT-PCR for DNMT1, DNMT3A, DNMT3B, HMLH1, and HMSH2 genes, demonstrating that the down regulation of DNMT3A and DNMT3B genes, but not DNMT1, o…
Inhibition of DNA damage response at telomeres improves the detrimental phenotypes of Hutchinson–Gilford Progeria Syndrome
2019
Hutchinson–Gilford progeria syndrome (HGPS) is a genetic disorder characterized by premature aging features. Cells from HGPS patients express progerin, a truncated form of Lamin A, which perturbs cellular homeostasis leading to nuclear shape alterations, genome instability, heterochromatin loss, telomere dysfunction and premature entry into cellular senescence. Recently, we reported that telomere dysfunction induces the transcription of telomeric non-coding RNAs (tncRNAs) which control the DNA damage response (DDR) at dysfunctional telomeres. Here we show that progerin-induced telomere dysfunction induces the transcription of tncRNAs. Their functional inhibition by sequence-specific telomer…
Exome-Wide Association Study on Alanine Aminotransferase Identifies Sequence Variants in the GPAM and APOE Associated With Fatty Liver Disease.
2021
BACKGROUND & AIMS: Fatty liver disease (FLD) is a growing epidemic that is expected to be the leading cause of end-stage liver disease within the next decade. Both environmental and genetic factors contribute to the susceptibility of FLD. Several genetic variants contributing to FLD have been identified in exome-wide association studies. However, there is still a missing hereditability indicating that other genetic variants are yet to be discovered. METHODS: To find genes involved in FLD, we first examined the association of missense and nonsense variants with alanine amino transferase at an exome-wide level in 425,671 participants from the UK Biobank. We then validated genetic variants wit…
Clinical and molecular characterization of 112 single-center patients with Neurofibromatosis type 1.
2018
Abstract Background The aim of this retrospective study was to define clinical and molecular characteristics of a large sample of neurofibromatosis type 1 (NF1) patients, as well as to evaluate mutational spectrum and genotype-phenotype correlation. NF1 is a relatively common neurogenetic disorder (1:2500–1:3000 individuals). It is caused by mutations of the NF1 gene on chromosome 17ql1.2, with autosomal dominant pattern of inheritance and wide phenotypical variability. Café-au-lait spots (CALs), cutaneous and/or subcutaneous neurofibromas (CNFs/SCNFs), skinfold freckling, skeletal abnormalities, Lisch nodules of the iris and increased risk of learning and intellectual disabilities, as well…
Oxidative stress and exceptional human longevity: Systematic review.
2020
Oxidative stress (OS) has been previously linked to the aging process, as have some diseases and geriatric syndromes as frailty and sarcopenia. The aim of the present study was to perform a systematic review on oxidative stress activity and extreme longevity in humans.We conducted a systematic literature review following the PRISMA guidelines. Observational studies assessing OS-biomarkers and/or antioxidants in long-lived individuals (97 years old or over) comparing them to those of one or more age groups, (at least one of which from comprising elderly subjects) were considered for inclusion. A narrative synthesis was planned. Quality of selected studies was assessed using the Newcastle-Ott…
Effects of ibuprofen and carbamazepine on the ion transport system and fatty acid metabolism of temperature conditioned juveniles of Solea senegalens…
2018
The increasing presence of pharmaceuticals in aquatic environments in the last decades, derived from human and veterinary use, has become an important environmental problem. Previous studies have shown that ibuprofen (IB) and carbamazepine (CBZ) modify physiological and biochemical processes in Senegalese sole (Solea senegalensis) in a temperature-dependent manner. In other vertebrates, there is evidence that both of these pharmaceuticals interfere with the ‘arachidonic acid (AA) cascade’, which is responsible for the biosynthesis of numerous enzymes that are involved in the osmoregulatory process. The present work aims to study the temperature-dependent effects of these two pharmaceuticals…
TheGCA1gene encodes a glycosidase-like protein in the cell wall ofCandida albicans
2016
Candida albicans Gca1p is a putative glucoamylase enzyme which contains 946 amino acids, 11 putative sites for N -glycosylation and 9 for O -glycosylation. Gca1p was identified in β-mercaptoethanol extracts from isolated cell walls of strain C. albicans SC5314 and it is involved in carbohydrate metabolism. The significance and the role of this protein within the cell wall structure were studied in the corresponding mutants. The homozygous mutant showed that GCA1 was not an essential gene for cell viability. Subsequent phenotypic analysis performed in the mutants obtained did not show significant difference in the behavior of mutant when compared with the wild strain SC5314. Zymoliase, Calco…
Structures of collagen IV globular domains: insight into associated pathologies, folding and network assembly
2018
15 páginas, 6 figuras, 1 tabla.