Search results for "Gene Deletion"
showing 10 items of 159 documents
Reconstructing the ancestor of Mycobacterium leprae: The dynamics of gene loss and genome reduction
2007
We have reconstructed the gene content and order of the last common ancestor of the human pathogens Mycobacterium leprae and Mycobacterium tuberculosis. During the reductive evolution of M. leprae, 1537 of 2977 ancestral genes were lost, among which we found 177 previously unnoticed pseudogenes. We find evidence that a massive gene inactivation took place very recently in the M. leprae lineage, leading to the loss of hundreds of ancestral genes. A large proportion of their nucleotide content (∼89%) still remains in the genome, which allowed us to characterize and date them. The age of the pseudogenes was computed using a new methodology based on the rates and patterns of substitution in the…
The Candida albicans pH-regulated KER1 gene encodes a lysine/glutamic-acid-rich plasma-membrane protein that is involved in cell aggregation.
2004
Immunoscreening of aCandida albicanscDNA library with a polyclonal germ-tube-specific antibody (pAb anti-gt) resulted in the isolation of a gene encoding a lysine/glutamic-acid-rich protein, which was consequently designatedKER1. The nucleotide and deduced amino acid sequences of this gene displayed no significant homology with any other known sequence.KER1encodes a 134 kDa lysine (14·5 %)/glutamic acid (16·7 %) protein (Ker1p) that contains two potential transmembrane segments.KER1was expressed in a pH-conditional manner, with maximal expression at alkaline pH and lower expression at pH 4·0, and was regulated byRIM101. A Δker1/Δker1null mutant grew normally but was hyperflocculant under ge…
A nonsense mutation abrogates production of a functional enterotoxin A in Clostridium difficile toxinotype VIII strains of serogroups F and X.
1999
Clostridium difficile strains of toxinotype VIII from serogroups F and X are described as toxin B-positive, toxin A-negative (TcdB+ A-), although they harbour almost the entire tcdA gene. To identify the reason for the lack of TcdA detection, we analyzed catalytic and ligand domains of TcdA-1470 of the type strain of serogroup F, strain 1470. Using recombinant fragments, the C-terminal immunodominant ligand domain TcdA3-1470, spanning amino acid residues 1694-2711 (corresponding to VPI 10463 sequence), was detected in Western blots. Similar experiments using the recombinant N-terminal catalytic fragment TcdAc1-2-1470 (amino acid positions 1-544) failed. In addition, this fragment showed no …
Illumina-based RiboMethSeq approach for mapping of 2'-O-Me residues in RNA
2016
International audience; RNA 2'-O-methylation is one of the ubiquitous nucleotide modifications found in many RNA types from Bacteria, Archaea and Eukarya. RNAs bearing 2'-O-methylations show increased resistance to degradation and enhanced stability in helices. While the exact role of each 2'-O-Me residue remained elusive, the catalytic protein Fibrillarin (Nop1 in yeast) responsible for 2'-O-methylation in eukaryotes, is associated with human pathologies. Therefore, there is an urgent need to precisely map and quantify hundreds of 2'-O-Me residues in RNA using high-throughput technologies. Here, we develop a reliable protocol using alkaline fragmentation of total RNA coupled to a commonly …
The loss of the inducible Aspergillus carbonarius MFS transporter MfsA leads to ochratoxin A overproduction
2014
Ochratoxin A (OTA), a nephrotoxic compound produced by certain Aspergillus and Penicillium species, is one of the most abundant mycotoxins in food commodities. Aspergillus carbonarius is the main source of OTA in wine, grape juice and dried vine fruits. Although many studies have focused on OTA production by A. carbonarius, little is known about the genes related to OTA production and transport. We have found a transporter that belongs to the major facilitator superfamily (MfsA) which is highly expressed with a 102-fold induction in an ochratoxigenic A. carbonarius strain compared to a low OTA producer strain. The encoding mfsA gene shows similarity to the multidrug efflux transporter flu1 …
The yeast inositol monophosphatase is a lithium- and sodium-sensitive enzyme encoded by a non-essential gene pair
1999
Inositol monophosphatases (IMPases) are lithium-sensitive enzymes that participate in the inositol cycle of calcium signalling and in inositol biosynthesis. Two open reading frames (YHR046c and YDR287w) with homology to animal and plant IMPases are present in the yeast genome. The two recombinant purified proteins were shown to catalyse inositol-1-phosphate hydrolysis sensitive to lithium and sodium. A double gene disruption had no apparent growth defect and was not auxotroph for inositol. Therefore, lithium effects in yeast cannot be explained by inhibition of IMPases and inositol depletion, as suggested for animal systems. Overexpression of yeast IMPases increased lithium and sodium toler…
Exon deletions of the phenylalanine hydroxylase gene in Italian hyperphenylalaninemics
2009
A consistent finding of many studies describing the spectrum of mutant phenylalanine hydroxylase (PAH) alleles underlying hyperphenylalaninemia is the impossibility of achieving a 100% mutation ascertainment rate using conventional gene-scanning methods. These methods include denaturing gradient gel electrophoresis (DGGE), denaturing high performance liquid chromatography (DHPLC), and direct sequencing. In recent years, it has been shown that a significant proportion of undetermined alleles consist of large deletions overlapping one or more exons. These deletions have been difficult to detect in compound heterozygotes using gene-scanning methods due to a masking effect of the non-deleted al…
Differential Roles of JNK in ConA/GalN and ConA-Induced Liver Injury in Mice
2008
Tumor necrosis factor-alpha-mediated liver injury can be induced by several different means; however, the signaling events and mechanisms of cell death are likely different. We investigated the mechanism of both apoptotic and necrotic hepatocyte cell death as well as the role of c-Jun NH2-terminal kinase (JNK) in the ConA and ConA/D-galactosamine (GalN) models of murine liver injury. ConA alone induced primarily necrotic cell death with no caspase activation, whereas ConA/GalN induced apoptosis in addition to necrotic cell death. The bi-modal death pattern in the ConA/GalN model was confirmed by the use of transgenic mice expressing a dominant-negative form of Fas-associated death domain in…
Caspase-8 regulates TNF-alpha induced epithelial necroptosis and terminal ileitis
2011
Two groups identify the regulation of death-receptor-induced necroptosis as an epithelial intrinsic mechanism that is important for the maintenance of immune homeostasis and the prevention of intestinal inflammation in mice. Welz et al. describe an unexpected physiological function for FADD (Fas-associated protein with death domain), an adaptor protein required for death-receptor-induced apoptosis. Mice with intestinal epithelial specific knockout of FADD develop severe colon inflammation due to increased death of FADD-deficient colonic epithelial cells. Gunther et al. report a novel and unexpected function of caspase-8 in maintaining immune homeostasis in the gut. Caspase-8 expression by g…
Features of TAP-independent MHC class I ligands revealed by quantitative mass spectrometry.
2008
TAP is responsible for transferring cytosolic peptides into the ER, where they can be loaded onto MHC molecules. Deletion of TAP results in a drastic reduction of MHC class I surface expression and alters the presented peptide pattern. This key molecule in antigen processing is tackled by several viruses and lost in some tumors, rendering the altered cells less vulnerable to T cell-based immune surveillance. Using the TAP-deficient cell line LCL721.174 and its TAP-expressing progenitor cell line LCL721.45, we identified and quantified more than 160 HLA ligands, 50 of which were presented TAP-independently. Peptides which were predominantly presented on the TAP-deficient LCL721.174 cell line…