Search results for "Mutation."
showing 10 items of 2808 documents
Coordinated remodeling of cellular metabolism during iron deficiency through targeted mRNA degradation.
2004
AbstractIron (Fe) is an essential micronutrient for virtually all organisms and serves as a cofactor for a wide variety of vital cellular processes. Although Fe deficiency is the primary nutritional disorder in the world, cellular responses to Fe deprivation are poorly understood. We have discovered a posttranscriptional regulatory process controlled by Fe deficiency, which coordinately drives widespread metabolic reprogramming. We demonstrate that, in response to Fe deficiency, the Saccharomyces cerevisiae Cth2 protein specifically downregulates mRNAs encoding proteins that participate in many Fe-dependent processes. mRNA turnover requires the binding of Cth2, an RNA binding protein conser…
Giustizia ambientale e recupero delle aree verdi: il caso di Palermo
2021
L’urban shrinkage è diventata una questione centrale tanto nel dibattito scientifico quanto nell’agenda politica di diverse città europee. Secondo i dati EUROSTAT (2019), circa il 40% delle città europee con più di 200.000 abitanti stanno perdendo popolazione; una contrazione che si esplicita maggiormente, sotto il profilo spaziale, in una progressiva sottoutilizzazione del patrimonio edificato, così come nel contestuale incremento di aree e terreni in stato di abbandono. In questo quadro controverso di mutazione strutturale della città, così come l’abbiamo conosciuta, le politiche urbane alla prova in Europa tentano di declinare la decrescita quale occasione strategica di investimento sull…
Cellular UDP-Glucose Deficiency Caused by a Single Point Mutation in the UDP-Glucose Pyrophosphorylase Gene
1997
We previously isolated a mutant cell that is the only mammalian cell reported to have a persistently low level of UDP-glucose. In this work we obtained a spontaneous revertant whose UDP-glucose level lies between those found in the wild type and the mutant cell. The activity of UDP-glucose pyrophosphorylase (UDPG:PP), the enzyme that catalyzes the formation of UDP-glucose, was in the mutant 4% and in the revertant 56% of the activity found in the wild type cell. Sequence analysis of UDPG: PP cDNAs from the mutant cell showed one missense mutation, which changes amino acid residue 115 from glycine to aspartic acid. The substituted glycine is located within the largest stretch of strictly con…
UDP-glucose deficiency in a mutant cell line protects against glucosyltransferase toxins from Clostridium difficile and Clostridium sordellii.
1996
Abstract We have previously isolated a fibroblast mutant cell with high resistance to the two Rho-modifying glucosyltransferase toxins A and B of Clostridium difficile. We demonstrate here a low level of UDP-glucose in the mutant, which explains its toxin resistance since: (i) to obtain a detectable toxin B-mediated Rho modification in lysates of mutant cells, addition of UDP-glucose was required, and it promoted the Rho modification dose-dependently; (ii) high pressure liquid chromatography analysis of nucleotide extracts of cells indicated that the level of UDP-glucose in the mutant (0.8 nmol/106 cells) was lower than in the wild type (3.7 nmol/106 cells); and (iii) sensitivity to toxin B…
Study of USH1 Splicing Variants through Minigenes and Transcript Analysis from Nasal Epithelial Cells
2012
Usher syndrome type I (USH1) is an autosomal recessive disorder characterized by congenital profound deafness, vestibular areflexia and prepubertal retinitis pigmentosa. The first purpose of this study was to determine the pathologic nature of eighteen USH1 putative splicing variants found in our series and their effect in the splicing process by minigene assays. These variants were selected according to bioinformatic analysis. The second aim was to analyze the USH1 transcripts, obtained from nasal epithelial cells samples of our patients, in order to corroborate the observed effect of mutations by minigenes in patient’s tissues. The last objective was to evaluate the nasal ciliary beat fre…
VDR MUTATION IN TWO SISTERS: PHENOTYPE VARIABILITY AND CLINICAL OUTCOME
2017
Objectives: Hereditary vitamin D-resistant rickets (HVDRR) is an autosomal recessive disease secondary to the mutation of vitamin D receptor (VDR) gene. These children show an early onset of rickets and in some of them alopecia is associated. Methods: We describe clinical features and laboratory findings in two sisters affected by HVDRR, as well as their response to treatment. Results: The first born is now 4 years old and had a severe and resistant hypocalcaemia, with low response to high doses of calcium per os, the requirement of intravenous infusion of calcium for a prolonged period, hypocalcaemic seizures resolved with high doses of intravenous calcium and high doses of vitamin D. Clin…
Spatial and temporal distribution of SARS-CoV-2 diversity circulating in wastewater
2022
Wastewater-based epidemiology (WBE) has proven to be an effective tool for epidemiological surveillance of SARS-CoV-2 during the current COVID-19 pandemic. Furthermore, combining WBE together with high-throughput sequencing techniques can be useful for the analysis of SARS-CoV-2 viral diversity present in a given sample. The present study focuses on the genomic analysis of SARS-CoV-2 in 76 sewage samples collected during the three epidemiological waves that occurred in Spain from 14 wastewater treatment plants distributed throughout the country. The results obtained demonstrate that the metagenomic analysis of SARS-CoV-2 in wastewater allows the detection of mutations that define the B.1.1.…
Endothelin-1-Mediated Drug Resistance in EGFR-Mutant Non-Small Cell Lung Carcinoma.
2020
Abstract Progression on therapy in non-small cell lung carcinoma (NSCLC) is often evaluated radiographically, however, image-based evaluation of said therapies may not distinguish disease progression due to intrinsic tumor drug resistance or inefficient tumor penetration of the drugs. Here we report that the inhibition of mutated EGFR promotes the secretion of a potent vasoconstrictor, endothelin-1 (EDN1), which continues to increase as the cells become resistant with a mesenchymal phenotype. As EDN1 and its receptor (EDNR) is linked to cancer progression, EDNR-antagonists have been evaluated in several clinical trials with disappointing results. These trials were based on a hypothesis that…
Tbx1 regulates Vegfr3 and is required for lymphatic vessel development
2010
Defects in lymphangiogenesis are added to the broad clinical manifestations of DiGeorge syndrome, caused by deletion of the T box transcription factor Tbx1.
Investigation on a MMACHC mutant from cblC disease: The c.394C>T variant
2022
The cblC disease is an inborn disorder of the vitamin B12 (cobalamin, Cbl) metabolism characterized by methylmalonic aciduria and homocystinuria. The clinical consequences of this disease are devastating and, even when early treated with current therapies, the affected children manifest symptoms involving vision, growth, and learning. The illness is caused by mutations in the gene codifying for MMACHC, a 282aa protein that transports and transforms the different Cbl forms. Here we present data on the structural properties of the truncated protein p.R132X resulting from the c.394C > T mutation that, along with c.271dupA and c.331C > T, is among the most common mutations in cblC. Althou…