De novo variants in SP9 cause a novel form of interneuronopathy characterized by intellectual disability, autism spectrum disorder, and epilepsy with variable expressivity

Purpose: Interneuronopathies are a group of neurodevelopmental disorders characterized by deficient migration and differentiation of gamma-aminobutyric acidergic interneurons resulting in a broad clinical spectrum, including autism spectrum disorders, early-onset epileptic encephalopathy, intellectual disability, and schizophrenic disorders. SP9 is a transcription factor belonging to the Krüppel-like factor and specificity protein family, the members of which harbor highly conserved DNA-binding domains. SP9 plays a central role in interneuron development and tangential migration, but it has not yet been implicated in a human neurodevelopmental disorder. Methods: Cases with SP9 variants were collected through international data-sharing networks. To address the specific impact of SP9 variants, in silico and in vitro assays were carried out. Results: De novo heterozygous variants in SP9 cause a novel form of interneuronopathy. SP9 missense variants affecting the glutamate 378 amino acid result in severe epileptic encephalopathy because of hypomorphic and neomorphic DNA-binding effects, whereas SP9 loss-of-function variants result in a milder phenotype with epilepsy, developmental delay, and autism spectrum disorder. Conclusion: De novo heterozygous SP9 variants are responsible for a neurodevelopmental disease. Interestingly, variants located in conserved DNA-binding domains of KLF/SP family transcription factors may lead to neomorphic DNA-binding functions resulting in a combination of loss- and gain-of-function effects

COVID-19 symptoms at hospital admission vary with age and sex: results from the ISARIC prospective multinational observational study

Background: The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms. Methods: International, prospective observational study of 60 109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms. Results: ‘Typical’ symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80, 79, 69%; at least one 95%). They were reported less frequently in children (≤ 18 years: 69, 48, 23; 85%), older adults (≥ 70 years: 61, 62, 65; 90%), and women (66, 66, 64; 90%; vs. men 71, 70, 67; 93%, each P < 0.001). The most common atypical presentations under 60 years of age were nausea and vomiting and abdominal pain, and over 60 years was confusion. Regression models showed significant differences in symptoms with sex, age and country. Interpretation: This international collaboration has allowed us to report reliable symptom data from the largest cohort of patients admitted to hospital with COVID-19. Adults over 60 and children admitted to hospital with COVID-19 are less likely to present with typical symptoms. Nausea and vomiting are common atypical presentations under 30 years. Confusion is a frequent atypical presentation of COVID-19 in adults over 60 years. Women are less likely to experience typical symptoms than men

A partir d'un élevage d'escargots à l'école : comment comprendre la notion du "vivant" ?

Life is a complex concept that evolves throughout schooling. Young children, including those in kindergarten, have erroneous representations that distort the acquisition of this concept. The introduction of snail farming in the junior and middle class allows the observation of the biological characteristics of living things: nutrition, reproduction, death, movement, growth. This is how the bases will be acquired to build this concept. The activities carried out upstream make it possible to define common biological specificities at the origins of the concept of “living”.Le vivant est un concept complexe qui évolue tout au long de la scolarité. Les jeunes enfants, dont ceux de l’école maternelle, ont des représentations erronées qui faussent l’acquisition de ce concept. L’introduction d’un élevage d’escargot en classe de petite et moyenne section permet d’observer les caractéristiques biologiques du vivant : la nutrition, la reproduction, la mort, le mouvement, la croissance. C’est ainsi que les bases vont être acquises pour construire ce concept. Les activités menées en amont permettent de définir des spécificités biologiques communes à l’origines du concept du « vivant »

Rétablissement du flétan atlantique dans le golfe du Saint-Laurent : état des connaissances biologiques et défis de gestion

Le flétan atlantique (Hippoglossus hippoglossus) est le poisson de fond possédant la plus haute valeur commerciale par unité de poids dans le golfe du Saint-Laurent (GSL). Il constitue ainsi une ressource importante sur le plan socio-économique au Québec et dans les provinces de l’Atlantique. Les débarquements de flétan atlantique y sont en constante augmentation depuis les années 2000, après un effondrement du stock au début des années 1950 qui a été suivi d’une longue période de faible abondance. En 2019, les débarquements (plus de 1 383 tonnes) étaient les plus importants des 60 dernières années. À la suite de ce retour marqué, de meilleures connaissances sur l’écologie larvaire et l’utilisation de l’habitat tout au long de l’ontogénie sont essentielles pour assurer une gestion durable du stock. Nous présentons l’historique de l’exploitation du stock de flétan atlantique du GSL et l’état actuel des connaissances de l’espèce dans cette unité de gestion. Nous abordons également les défis auxquels les gestionnaires font face en vue d’assurer une exploitation durable, et les projets de recherche en cours visant à combler les lacunes dans nos connaissances. Finalement, nous abordons les enjeux spécifiques à l’instauration d’une pêche récréative hivernale durable pour le flétan atlantique dans le fjord du Saguenay.Atlantic halibut (Hippoglossus hippoglossus) is the groundfish with the highest commercial value per unit weight and is thus an important socio-economic resource in Québec and the Atlantic provinces (Canada). Landings of Atlantic halibut from the Gulf of St. Lawrence have been steadily increasing since the early 2000s, after a stock collapse in the early 1950s that was followed by a long period of low abundance. In 2019, landings exceeded 1,383 tons, the highest in the last 60 years. Following this strong return, improved knowledge of larval ecology and habitat use throughout its ontogeny is essential for sustainable management of the stock. This paper presents a history of the Atlantic halibut harvest from the Gulf of St. Lawrence and the current state of knowledge concerning this management unit of the species. It also outlines the challenges managers face in ensuring a sustainable fishery and the research currently underway to fill key knowledge gaps. Finally, the specific issues involved in establishing a sustainable recreational Atlantic halibut ice fishery in the Saguenay Fjord are discussed

Novel approach to identify phenoloxidases inhibitors: Optimization of spectrophotometric MBTH assay for high throughput use enzymatic assays and analysis

International audienceThis study presents a miniaturized 3-methyl-2-benzothiazolinone hydrazone hydrochloride-assay (MBTHassay) 1 , optimized for high-throughput measurement of shrimp phenol oxidase activities and the screening of potential inhibitors of post-mortem melanosis. To validate this approach, assay parameters, including limit of detection and dynamic range, were compared to values obtained for DOPAchrome-assay, used here as a reference method. A reliable high-throughput automatized analysis was also performed, under standardized parameters, in order to compare and characterize 40 potential inhibitors of phenol oxidase activities. Among the selected molecules, twenty showed inhibitory action. Enzyme-inhibitor dissociation constant (K i), median inhibitor concentration (IC 50) and inhibition modes could be determined for nine of them. 4-Hexylresorcinol, Nphenylthiourea L-cystein and glutathione displayed K i values lower than sulfite salts (Na 2 S 2 O 5 and Na 2 SO 3) used as positive controls

Les effets du jumelage des infrastructures lourdes de transport sur les territoires : quels enseignements?

This article reports a research on the effects of pairing of heavy infrastructures such as motorways and high speed lines railways on the functioning and perception of the territory. The ecological impact, effects on the evolution and perception of landscapes as well as governance issues and social acceptability in nearby areas have been specifically studied in three representative of the major types of land pairing observed in France. The comparison of the different elements from the research shows an apparent contradiction on scales of analysis of the appropriateness of the pairing. If it offers an overall benefit for land management with space saving and limiting fragmentation, it also causes a consumption of land with the creation of interstitial spaces, and a strong polarization of space. From the societal perspective, the advantages and disadvantages of the pairing are also related on scales thinking and posture of the actors interviewed vis-à-vis spatial or organizational cuts, or perception of nuisances. Pairing is therefore more a process than a technical solution. Directed downstream, it does not allow for synergies with the territory, but only responds to some isolated subjects like space consumption

Les effets du jumelage des infrastructures lourdes de transport sur les territoires : quels enseignements?

This article reports a research on the effects of pairing of heavy infrastructures such as motorways and high speed lines railways on the functioning and perception of the territory. The ecological impact, effects on the evolution and perception of landscapes as well as governance issues and social acceptability in nearby areas have been specifically studied in three representative of the major types of land pairing observed in France. The comparison of the different elements from the research shows an apparent contradiction on scales of analysis of the appropriateness of the pairing. If it offers an overall benefit for land management with space saving and limiting fragmentation, it also causes a consumption of land with the creation of interstitial spaces, and a strong polarization of space. From the societal perspective, the advantages and disadvantages of the pairing are also related on scales thinking and posture of the actors interviewed vis-à-vis spatial or organizational cuts, or perception of nuisances. Pairing is therefore more a process than a technical solution. Directed downstream, it does not allow for synergies with the territory, but only responds to some isolated subjects like space consumption

Metabolomics signatures of a subset of RET variants according to their oncogenic risk level

International audienc

De novo variants in SP9 cause a novel form of interneuronopathy characterized by intellectual disability, autism spectrum disorder, and epilepsy with variable expressivity

International audiencePurpose: Interneuronopathies are a group of neurodevelopmental disorders characterized bydeficient migration and differentiation of gamma-aminobutyric acidergic interneurons resultingin a broad clinical spectrum, including autism spectrum disorders, early-onset epilepticencephalopathy, intellectual disability, and schizophrenic disorders. SP9 is a transcriptionfactor belonging to the Kr¨uppel-like factor and specificity protein family, the members ofwhich harbor highly conserved DNA-binding domains. SP9 plays a central role ininterneuron development and tangential migration, but it has not yet been implicated in ahuman neurodevelopmental disorder.Methods: Cases with SP9 variants were collected through international data-sharing networks.To address the specific impact of SP9 variants, in silico and in vitro assays were carried out.Results: De novo heterozygous variants in SP9 cause a novel form of interneuronopathy. SP9missense variants affecting the glutamate 378 amino acid result in severe epileptic encephalopathybecause of hypomorphic and neomorphic DNA-binding effects, whereas SP9 loss-offunctionvariants result in a milder phenotype with epilepsy, developmental delay, and autismspectrum disorder.Conclusion: De novo heterozygous SP9 variants are responsible for a neurodevelopmentaldisease. Interestingly, variants located in conserved DNA-binding domains of KLF/SP familytranscription factors may lead to neomorphic DNA-binding functions resulting in acombination of loss- and gain-of-function effects