Search results for "Mutagenesi"
showing 10 items of 2484 documents
HCN1 mutation spectrum: from neonatal epileptic encephalopathy to benign generalized epilepsy and beyond
2018
International audience; Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels control neuronal excitability and their dysfunction has been linked to epileptogenesis but few individuals with neurological disorders related to variants altering HCN channels have been reported so far. In 2014, we described five individuals with epileptic encephalopathy due to de novo HCN1 variants. To delineate HCN1-related disorders and investigate genotype-phenotype correlations further, we assembled a cohort of 33 unpublished patients with novel pathogenic or likely pathogenic variants: 19 probands carrying 14 different de novo mutations and four families with dominantly inherited variants segre…
Insights into the Structure of the Vip3Aa Insecticidal Protein by Protease Digestion Analysis
2017
Vip3 proteins are secretable proteins from Bacillus thuringiensis whose mode of action is still poorly understood. In this study, the activation process for Vip3 proteins was closely examined in order to better understand the Vip3Aa protein stability and to shed light on its structure. The Vip3Aa protoxin (of 89 kDa) was treated with trypsin at concentrations from 1:100 to 120:100 (trypsin:Vip3A, w:w). If the action of trypsin was not properly neutralized, the results of SDS-PAGE analysis (as well as those with Agrotis ipsilon midgut juice) equivocally indicated that the protoxin could be completely processed. However, when the proteolytic reaction was efficiently stopped, it was revealed t…
Phosphorylation and proteasome recognition of the mRNA- binding protein Cth2 facilitates yeast adaptation to iron deficiency
2018
Iron is an indispensable micronutrient for all eukaryotic organisms due to its participation as a redox cofactor in many metabolic pathways. Iron imbalance leads to the most frequent human nutritional deficiency in the world. Adaptation to iron limitation requires a global reorganization of the cellular metabolism directed to prioritize iron utilization for essential processes. In response to iron scarcity, the conserved Saccharomyces cerevisiae mRNA-binding protein Cth2, which belongs to the tristetraprolin family of tandem zinc finger proteins, coordinates a global remodeling of the cellular metabolism by promoting the degradation of multiple mRNAs encoding highly iron-consuming proteins.…
The Crystal Structure of Gurmarin, a Sweet Taste–Suppressing Protein: Identification of the Amino Acid Residues Essential for Inhibition
2018
International audience; Gurmarin is a highly specific sweet-taste suppressing protein in rodents that is isolated from the Indian plant Gymnemasylvestre. Gurmarin consists of 35 amino acid residues containing three intramolecular disulfide bridges that form a cystine knot. Here, we report the crystal structure of gurmarin at a 1.45 Å resolution and compare it with previously reported NMR solution structures. The atomic structure at this resolution allowed us to identify a very flexible region consisting of hydrophobic residues. Some of these amino acid residues had been identified as a putative binding site for the rat sweet taste receptor in a previous study. By combining alanine-scanning …
MycoKey Round Table Discussions of Future Directions in Research on Chemical Detection Methods, Genetics and Biodiversity of Mycotoxins
2018
MycoKey, an EU-funded Horizon 2020 project, includes a series of “Roundtable Discussions” to gather information on trending research areas in the field of mycotoxicology. This paper includes summaries of the Roundtable Discussions on Chemical Detection and Monitoring of mycotoxins and on the role of genetics and biodiversity in mycotoxin production. Discussions were managed by using the nominal group discussion technique, which generates numerous ideas and provides a ranking for those identified as the most important. Four questions were posed for each research area, as well as two questions that were common to both discussions. Test kits, usually antibody based, were one major focus of the…
New Insights into the Genome Organization of Yeast Killer Viruses Based on “Atypical” Killer Strains Characterized by High-Throughput Sequencing
2017
Viral M-dsRNAs encoding yeast killer toxins share similar genomic organization, but no overall sequence identity. The dsRNA full-length sequences of several known M-viruses either have yet to be completed, or they were shorter than estimated by agarose gel electrophoresis. High-throughput sequencing was used to analyze some M-dsRNAs previously sequenced by traditional techniques, and new dsRNAs from atypical killer strains of Saccharomyces cerevisiae and Torulaspora delbrueckii. All dsRNAs expected to be present in a given yeast strain were reliably detected and sequenced, and the previously-known sequences were confirmed. The few discrepancies between viral variants were mostly located aro…
Developmental effects of the protein kinase inhibitor kenpaullone on the sea urchin embryo
2017
The selection and validation of bioactive compounds require multiple approaches, including in-depth analyses of their biological activity in a whole-animal context. We exploited the sea urchin embryo in a rapid, medium-scale range screening to test the effects of the small synthetic kinase inhibitor kenpaullone. We show that sea urchin embryos specifically respond to this molecule depending on both dose and timing of administration. Phenotypic effects of kenpaullone are not immediately visible, since this molecule affects neither the fertilization nor the spatial arrangement of blastomeres at early developmental stages. Nevertheless, kenpaullone exposure from the beginning of embryogenesis …
Molecular Characterization of Coxsackievirus B5 Isolates from Sewage, Italy 2016–2017
2019
Hereby, the partial Viral Protein 1 sequences of Coxsackievirus B5 (CV-B5) from sewage samples, collected in Italy from 2016 to 2017, were compared with those available in GenBank from clinical samples. Phylogenetic analysis highlighted: (I) the predominant circulation of CV-B5 genogroup B in Italy, and (II) the presence of two new sub-genogroups.
Evaluation of Alternaria mycotoxins in strawberries: quantification and storage condition
2016
Alternariol (AOH), alternariol methyl ether (AME) and tentoxin (TEN) are Alternaria mycotoxins produced by the most common post-harvest pathogens of fruits. The production of these metabolites depends on several environmental factors, mainly temperature, water activity, pH and the technological treatments that have been applied to the product. In this study, the occurrence of AOH, AME and TEN was evaluated in strawberries samples stored at different temperatures ranges (at 22 ± 2 or 6 ± 2°C) and different periods (up to 1 month) simulating the current practice of consumer's storage conditions. Sample extraction was performed using a liquid-liquid extraction method prior to LC-MS/MS analysis…
Viral replication modes in single-peak fitness landscapes: A dynamical systems analysis
2017
Positive-sense, single-stranded RNA viruses are important pathogens infecting almost all types of organisms. Experimental evidence from distributions of mutations and from viral RNA amplification suggest that these pathogens may follow different RNA replication modes, ranging from the stamping machine replication (SMR) to the geometric replication (GR) mode. Although previous theoretical work has focused on the evolutionary dynamics of RNA viruses amplifying their genomes with different strategies, little is known in terms of the bifurcations and transitions involving the so-called error threshold (mutation-induced dominance of mutants) and lethal mutagenesis (extinction of all sequences du…