The novel homozygous KCNJ10 c.986T>C (p.(Leu329Pro)) variant is pathogenic for the SeSAME/EAST homologue in Malinois dogs.

SeSAME/EAST syndrome is a multisystemic disorder in humans, characterised by seizures, sensorineural deafness, ataxia, developmental delay and electrolyte imbalance. It is exclusively caused by homozygous or compound heterozygous variations in the KCNJ10 gene. Here we describe a similar syndrome in two families belonging to the Malinois dog breed, based on clinical, neurological, electrodiagnostic and histopathological examination. Genetic analysis detected a novel pathogenic KCNJ10 c.986T>C (p.(Leu329Pro)) variant that is inherited in an autosomal recessive way. This variant has an allele frequency of 2.9% in the Belgian Malinois population, but is not found in closely related dog breeds or in dog breeds where similar symptoms have been already described. The canine phenotype is remarkably similar to humans, including ataxia and seizures. In addition, in half of the dogs clinical and electrophysiological signs of neuromyotonia were observed. Because there is currently no cure and treatment is nonspecific and unsatisfactory, this canine translational model could be used for further elucidating the genotype/phenotype correlation of this monogenic multisystem disorder and as an excellent intermediate step for drug safety testing and efficacy evaluations before initiating human studies

CMS physics technical design report : Addendum on high density QCD with heavy ions

Peer reviewe

Adaptation of Classical Evaluation Methods to a Young Audience with Autism Spectrum Disorders

International audienceIn order to validate the usability and utility of an application, it is necessary to evaluate it. Many methods exist. The choice of these is defined by the availability of the application and the end users. But other parameters impact this choice as the context of use of the tool as well as the specificities of the public. The methods most commonly used when the application and the users are available, rely predominantly on verbal exchanges, in individual and group interviews. We want to evaluate an application dedicated to a young audience with ASD (Autism Spectrum Disorders). Apart from this audience, there are difficulties in the areas of communication and social interactions. Therefore, how can we evaluate an application dedicated to this particular audience while involving it? We propose an adaptation of classical evaluation methods based on the environment and the human environment of the users.Afin de valider l’utilisabilité et l’utilité d’une application, il est nécessaire de l’évaluer. De nombreuses méthodes existent. Le choix de celles-ci est défini par la disponibilité de l'application et celle des utilisateurs finaux. Mais d’autres paramètres entrent en jeu dans ce choix comme le contexte d’utilisation de l’outil ainsi que les particularités du public. Les méthodes les plus communément utilisées lorsque l’application et les utilisateurs sont disponibles, reposent majoritairement sur des échanges verbaux, en entretiens individuels comme en groupe. Nous souhaitons évaluer une application dédiée à un jeune public avec TSA (Troubles du Spectre Autistique). Or ce public présente, entre autres, des difficultés dans les domaines de la communication et des interactions sociales. Dès lors, comment évaluer une application dédiée à ce public particulier tout en le faisant participer ? Nous proposons une adaptation des méthodes d’évaluation classiques en nous appuyant sur l'environnement et l'entourage humain des utilisateurs

G2 checkpoint control and G2 chromosomal radiosensitivity in cancer survivors and their families

Significant inter-individual variation in G2 chromosomal radiosensitivity, measured as radiation-induced chromatid-type aberrations in the subsequent metaphase, has been reported in peripheral blood lymphocytes of both healthy individuals and a range of cancer patients. One possible explanation for this variation is that it is driven, at least in part, by the efficiency of G2–M checkpoint control. The hypothesis tested in the current analysis is that increased G2 chromosomal radiosensitivity is facilitated by a less efficient G2–M checkpoint. The study groups comprised 23 childhood and adolescent cancer survivors, their 23 partners and 38 of their offspring (Group 1) and 29 childhood and young adult cancer survivors (Group 2). Following exposure to 0.5 Gy of 300 kV X-rays, lymphocyte cultures were assessed for both G2 checkpoint delay and G2 chromosomal radiosensitivity. In Group 1, the extent of G2 checkpoint delay was measured by mitotic inhibition. No statistically significant differences in G2 checkpoint delay were observed between the cancer survivors (P = 0.660) or offspring (P = 0.171) and the partner control group nor was there any significant relationship between G2 checkpoint delay and G2 chromosomal radiosensitivity in the cancer survivors (P = 0.751), the partners (P = 0.634), the offspring (P = 0.824) or Group 1 taken as a whole (P = 0.379). For Group 2, G2 checkpoint delay was assessed with an assay utilising premature chromosome condensation to distinguish cell cycle stage. No significant relationship between G2 checkpoint delay and G2 chromosomal radiosensitivity was found (P = 0.284). Thus, this study does not support a relationship between G2–M checkpoint efficiency and variation in G2 chromosomal radiosensitivity

The forward muon detector of L3

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