Expression of a bacterial effector, harpin N, causes increased resistance to fire blight in Pyrus communis

The rapid and effective activation of disease resistance responses is essential for plant defense against pathogen attack. These responses are initiated when pathogen-derived molecules (elicitors) are recognized by the host. In order to create novel mechanisms for fire blight resistance in pear, we have generated transgenic pears expressing the elicitor harpin Nea from Erwinia amylovora under the control of the constitutive promoter CaMV35S. The transient expression of hrpN Ea in pear cells did not provoke any apparent damage. Therefore, stable constitutive expression of hrpN Ea was studied in seventeen transgenic clones of the very susceptible cultivar "Passe Crassane.” Most transgenic clones displayed significant reduction of susceptibility to fire blight in vitro when inoculated by E. amylovora, which was positively correlated to their degree of expression of the transgene hrpN Ea . These results indicate that ectopic expression of a bacterial elicitor such as harpin Nea is a promising way to improve pear resistance to fire bligh

Simultaneous sequencing of 37 genes identified causative mutations in the majority of children with renal tubulopathies

The clinical diagnosis of inherited renal tubulopathies can be challenging as they are rare and characterized by significant phenotypic variability. Advances in sequencing technologies facilitate the establishment of a molecular diagnosis. Therefore, we determined the diagnostic yield of a next generation sequencing panel assessing relevant disease genes in children followed through three national networks with a clinical diagnosis of a renal tubulopathy. DNA was amplified with a kit provided by the European Consortium for High-Throughput Research in Rare Kidney Diseases with nine multiplex PCR reactions. This kit produced 571 amplicons covering 37 genes associated with tubulopathies followed by massive parallel sequencing and bioinformatic interpretation. Identified mutations were confirmed by Sanger sequencing. Overall, 384 index patients and 16 siblings were assessed. Most common clinical diagnoses were 174 patients with Bartter/Gitelman syndrome and 76 with distal renal tubular acidosis. A total of 269 different variants were identified in 27 genes, of which 95 variants were considered likely, 136 definitely pathogenic and 100 had not been described at annotation. These mutations established a genetic diagnosis in 245 of the index patients. Genetic testing changed the clinical diagnosis in 16 cases and provided insights into the phenotypic spectrum of the respective disorders. Our results demonstrate a high diagnostic yield of genetic testing in children with a clinical diagnosis of a renal tubulopathy, consistent with a predominantly genetic etiology in known disease genes. Thus, genetic testing helped establish a definitive diagnosis in almost two-thirds of patients thereby informing prognosis, management and genetic counseling

Specificity and Prevalence of Natural Bovine Antimannan Antibodies

Immune responses to the carbohydrate components of microorganisms, mediated both by antibodies and by lectins, are an important part of host defense. In the present experiments, the specificity and presence of natural bovine antibodies against mannan, a common fungal antigen, were examined by enzyme-linked immunosorbent assay (ELISA), using Saccharomyces cerevisiae mannan as an antigen. The results showed that all serum samples from animals of three age groups (newborn, calf, and adult) tested contained antimannan antibodies, and the titer of these antibodies increased significantly in adults. However, titers among individual adult cattle differed widely. Inhibition assays showed that yeast mannan was the strongest inhibitor. d-Mannose exhibited only a minor inhibitory effect at high concentrations. This suggests that most of these antibodies recognize an oligosaccharide-based epitope(s) different from those recognized by lectins. Cattle possess three serum C-type lectins (collectins) capable of recognizing mannan in a calcium-dependent manner. Addition of EDTA to the reaction did not reduce antibody binding, suggesting that the binding of these antibodies to mannan was not affected by the presence of collectin. The antibodies purified from either calf or adult serum by mannan-Sepharose affinity chromatography consisted of mainly immunoglobulin G (IgG) and a smaller amount of IgM. IgG1 was shown to be the dominant antimannan IgG isotype by isotype-specific ELISA. Together, these results demonstrate the production of natural antimannan antibodies in cattle in an age-dependent manner. These antibodies might be involved in defending the host against mannan-containing pathogens as a specific line of defense in conjunction with the innate response by lectins

A new MRI rating scale for progressive supranuclear palsy and multiple system atrophy: validity and reliability

AIM To evaluate a standardised MRI acquisition protocol and a new image rating scale for disease severity in patients with progressive supranuclear palsy (PSP) and multiple systems atrophy (MSA) in a large multicentre study. METHODS The MRI protocol consisted of two-dimensional sagittal and axial T1, axial PD, and axial and coronal T2 weighted acquisitions. The 32 item ordinal scale evaluated abnormalities within the basal ganglia and posterior fossa, blind to diagnosis. Among 760 patients in the study population (PSP = 362, MSA = 398), 627 had per protocol images (PSP = 297, MSA = 330). Intra-rater (n = 60) and inter-rater (n = 555) reliability were assessed through Cohen's statistic, and scale structure through principal component analysis (PCA) (n = 441). Internal consistency and reliability were checked. Discriminant and predictive validity of extracted factors and total scores were tested for disease severity as per clinical diagnosis. RESULTS Intra-rater and inter-rater reliability were acceptable for 25 (78%) of the items scored (≥ 0.41). PCA revealed four meaningful clusters of covarying parameters (factor (F) F1: brainstem and cerebellum; F2: midbrain; F3: putamen; F4: other basal ganglia) with good to excellent internal consistency (Cronbach α 0.75-0.93) and moderate to excellent reliability (intraclass coefficient: F1: 0.92; F2: 0.79; F3: 0.71; F4: 0.49). The total score significantly discriminated for disease severity or diagnosis; factorial scores differentially discriminated for disease severity according to diagnosis (PSP: F1-F2; MSA: F2-F3). The total score was significantly related to survival in PSP (p<0.0007) or MSA (p<0.0005), indicating good predictive validity. CONCLUSIONS The scale is suitable for use in the context of multicentre studies and can reliably and consistently measure MRI abnormalities in PSP and MSA. Clinical Trial Registration Number The study protocol was filed in the open clinical trial registry (http://www.clinicaltrials.gov) with ID No NCT00211224

Gentamicin in Hemodialyzed Critical Care Patients: Early Dialysis after Administration of a High Dose Should Be Considered

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Liens entre la pratique problématique des jeux vidéo, l'anxiété-trait, l'urgence négative et le niveau de dépression, au sein d'une population clinique de joueurs

International audienceProblématique : La littérature scientifique traitant de la pratique problématique des jeux vidéo, si elle n’a cessé de s’enrichir durant la dernière décennie, présente encore quelques lacunes, notamment concernant la compréhension des facteurs de risque. Cette étude se centre tout particulièrement sur les relations entre l’anxiété-trait, l’urgence négative, le niveau de dépression et la pratique problématique des jeux vidéo. Méthode : Cette étude interroge 38 joueurs en demande de soins, venus en évaluation au sein des locaux du Centre de Référence sur le Jeu Excessif, à Nantes. La procédure prévoit, en plus des mesures nécessaires à la confirmation ou l’infirmation des hypothèses, l’évaluation de caractéristiques sociodémographiques et d’autres plus spécifiques à la pratique de jeu. Le niveau de prévalence est aussi considéré. Un certain nombre d’outils validés sont utilisés. Il s’agit des versions françaises de l’inventaire d’anxiété état-trait, forme Y (STAI-Y), de l’ UPPS Impulsive Behavior Scale (UPPS), de l’inventaire abrégé de dépression de Beck (BDI-13) ainsi que de la Problem Videogame Playing Scale (PVP). Des régressions linéaires simples sont envisagées pour vérifier ou infirmer les hypothèses. Résultats : Les analyses effectuées montrent qu’il n’existe aucune relation linéaire entre le niveau d’urgence négative d’une part, celui de dépression d’autre part, et le niveau de pratique problématique. De plus, le niveau d’anxiété-trait ne permet pas d’expliquer significativement le niveau de pratique problématique des jeux vidéo. La prévalence observée au sein de cet échantillon varie de 3.85% à 76.92%, selon le format de mesure retenu. Les caractéristiques sociodémographiques et celles relatives à la pratique de jeu sont assez similaires à celles retrouvées dans la littérature. Discussion : Cette étude constitue l’une des rares études interrogeant une population clinique de joueurs de jeux vidéo, qui plus est en France. Les données obtenues, toutes limites prises en compte, montrent que les relations évoquées par des études effectuées sur des populations tout-venant de joueurs ne peuvent se généraliser automatiquement aux joueurs problématiques. En ce qui concerne les facteurs associés à la pratique problématique, force est de constater que les relations à envisager semblent être relativement complexes. Des interactions sont également à considérer. Des pistes pour les recherches futures sont finalement proposées

Liver fibrosis is associated with cutaneous inflammation in the imiquimod-induced murine model of psoriasiform dermatitis

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