63 research outputs found

    A Flavor Lactone Mimicking AHL Quorum-Sensing Signals Exploits the Broad Affinity of the QsdR Regulator to Stimulate Transcription of the Rhodococcal qsd Operon Involved in Quorum-Quenching and Biocontrol Activities

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    In many Gram-negative bacteria, virulence, and social behavior are controlled by quorum-sensing (QS) systems based on the synthesis and perception of N-acyl homoserine lactones (AHLs). Quorum-quenching (QQ) is currently used to disrupt bacterial communication, as a biocontrol strategy for plant crop protection. In this context, the Gram-positive bacterium Rhodococcus erythropolis uses a catabolic pathway to control the virulence of soft-rot pathogens by degrading their AHL signals. This QS signal degradation pathway requires the expression of the qsd operon, encoding the key enzyme QsdA, an intracellular lactonase that can hydrolyze a wide range of substrates. QsdR, a TetR-like family regulator, represses the expression of the qsd operon. During AHL degradation, this repression is released by the binding of the γ-butyrolactone ring of the pathogen signaling molecules to QsdR. We show here that a lactone designed to mimic quorum signals, γ-caprolactone, can act as an effector ligand of QsdR, triggering the synthesis of qsd operon-encoded enzymes. Interaction between γ-caprolactone and QsdR was demonstrated indirectly, by quantitative RT-PCR, molecular docking and transcriptional fusion approaches, and directly, in an electrophoretic mobility shift assay. This broad-affinity regulatory system demonstrates that preventive or curative quenching therapies could be triggered artificially and/or managed in a sustainable way by the addition of γ-caprolactone, a compound better known as cheap food additive. The biostimulation of QQ activity could therefore be used to counteract the lack of consistency observed in some large-scale biocontrol assays

    The first genetic landscape of inherited retinal dystrophies in Portuguese patients identifies recurrent homozygous mutations as a frequent cause of pathogenesis.

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    Inherited retinal diseases (IRDs) are a group of ocular conditions characterized by an elevated genetic and clinical heterogeneity. They are transmitted almost invariantly as monogenic traits. However, with more than 280 disease genes identified so far, association of clinical phenotypes with genotypes can be very challenging, and molecular diagnosis is essential for genetic counseling and correct management of the disease. In addition, the prevalence and the assortment of IRD mutations are often population-specific. In this work, we examined 230 families from Portugal, with individuals suffering from a variety of IRD diagnostic classes (270 subjects in total). Overall, we identified 157 unique mutations (34 previously unreported) in 57 distinct genes, with a diagnostic rate of 76%. The IRD mutational landscape was, to some extent, different from those reported in other European populations, including Spanish cohorts. For instance, the EYS gene appeared to be the most frequently mutated, with a prevalence of 10% among all IRD cases. This was, in part, due to the presence of a recurrent and seemingly founder mutation involving the deletion of exons 13 and 14 of this gene. Moreover, our analysis highlighted that as many as 51% of our cases had mutations in a homozygous state. To our knowledge, this is the first study assessing a cross-sectional genotype-phenotype landscape of IRDs in Portugal. Our data reveal a rather unique distribution of mutations, possibly shaped by a small number of rare ancestral events that have now become prevalent alleles in patients

    Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Distress Syndrome associated with COVID-19: An Emulated Target Trial Analysis.

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    RATIONALE: Whether COVID patients may benefit from extracorporeal membrane oxygenation (ECMO) compared with conventional invasive mechanical ventilation (IMV) remains unknown. OBJECTIVES: To estimate the effect of ECMO on 90-Day mortality vs IMV only Methods: Among 4,244 critically ill adult patients with COVID-19 included in a multicenter cohort study, we emulated a target trial comparing the treatment strategies of initiating ECMO vs. no ECMO within 7 days of IMV in patients with severe acute respiratory distress syndrome (PaO2/FiO2 <80 or PaCO2 ≥60 mmHg). We controlled for confounding using a multivariable Cox model based on predefined variables. MAIN RESULTS: 1,235 patients met the full eligibility criteria for the emulated trial, among whom 164 patients initiated ECMO. The ECMO strategy had a higher survival probability at Day-7 from the onset of eligibility criteria (87% vs 83%, risk difference: 4%, 95% CI 0;9%) which decreased during follow-up (survival at Day-90: 63% vs 65%, risk difference: -2%, 95% CI -10;5%). However, ECMO was associated with higher survival when performed in high-volume ECMO centers or in regions where a specific ECMO network organization was set up to handle high demand, and when initiated within the first 4 days of MV and in profoundly hypoxemic patients. CONCLUSIONS: In an emulated trial based on a nationwide COVID-19 cohort, we found differential survival over time of an ECMO compared with a no-ECMO strategy. However, ECMO was consistently associated with better outcomes when performed in high-volume centers and in regions with ECMO capacities specifically organized to handle high demand. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/)

    " Cuisine et service en pays bourguignon"

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    International audienceUCSB1A5FALezDLWGbsCZ0Qjg Programme Corema 27 mai à 14h00 " Cuisine et service en pays bourguignon" Virginie Hulet (Université de Tours) « La cuisine Bourguignonne dans les Pays-Bas Méridionaux à la Renaissance » Laurine Gobert (Université de Tours) : « Le service à la cour des ducs de Bourgogne à la fin du Moyen-âge »

    Combicontrol : autour de la jambe noire

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    Etude de la diversité génétique et inférence de liens phylogénétiques au sein de la section Mentha (Lamiaceae)

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    La taxonomie des menthes est très complexe du fait de leur polymorphisme morphologique, de leur capacité à s'hybrider et de leur domestication. La diversité génétique et les liens phylogénétiques ont été établis à l'intérieur de la section Mentha sur une collection de 62 accessions d'origines géographiques diverses, représentant les 4 espèces légitimes (M. suaveolens L., M. longifolia (L.) Huds., M. aquatica L., M. arvensis L.) et les 3 hybrides les plus cultivés (M. spicata L., M. x piperita L., M. x gracilis L.). Les méthodes d'empreintes génétiques AFLP (Amplified Fragment Length Polymorphism) et ISSR (Inter Simple Sequence Repeat) ont permis un typage par espèce en accord avec la classification actuelle et mettent en évidence le potentiel génétique de chaque espèce ainsi que les liens de parentés entre hybrides et espèces légitimes. Le séquençage d'ADN chloroplastique (intron trnL, espaceurs intergéniques trnL-trnF, psbA-trnH) révèle plusieurs haplotypes chez certaines espèces. Les séquences ITS (Internal Transcribed Spacers 1 et 2) montrent un polymorphisme intra et interspécifique et révèlent divers modes d'évolution des génomes polyploïdes et hybridesThe taxonomy of mints is complex because of their high morphological polymorphism, their ability to hybridize and their domestication. Genetic diversity and phylogenetic relationships of the section Mentha were established within a collection of 62 accessions of different geographical origins, representing the 4 legitimate species (M. suaveolens L., M. longifolia (L.) Huds., M. aquatica L., M. arvensis L.) and the 3 most cultivated hybrids (M. spicata L., M. x piperita L., M. x gracilis L.). The AFLP (Amplified Fragment Length Polymorphism) and ISSR (Inter Simple Sequence Repeat) DNA fingerprinting methods were performed. The results allow us to identify each species and are in accordance with the present classification. On the other hand, they assess the genetic potential of each species and the relationships between hybrids and legitimate species. The non-coding chloroplastic DNA (trnL intron, intergenic spacers trnL-trnF, psbA-trnH) shows several haplotypes within some species. The ITS (Internal Transcribed Spacers 1 and 2) sequences display intra and interspecific polymorphism and give information about evolution of polyploids and hybridsST ETIENNE-BU Sciences (422182103) / SudocSudocFranceF

    Role of the metallothioneins in metal regulation by the guillemot Uria aalge

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    Guillemots, like other seabird species living in the North Sea, appear to be heavily contaminated by copper. Metallothioneins are present in both liver and kidney but, at least in the specimens stranded along the Belgian coast, fail to maintain constant the copper, zinc and cadmium load of the high molecular weight soluble proteins of both organs, stressing the potential toxic role of these metals, mainly copper
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