Case report: an unexpected link between partial deletion of the SHANK3 gene and Heller’s dementia infantilis, a rare subtype of autism spectrum disorder

International audienceAbstractBackgroundDeletions and mutations involving the SHANK3 gene lead to a nonspecific clinical presentation with moderate to profound intellectual disability, severely delayed or absent speech, and autism spectrum disorders (ASD).Better knowledge of the clinical spectrum of SHANK3 haploinsufficiency is useful to facilitate clinical care monitoring and to guide molecular diagnosis, essential for genetic counselling.Case presentationHere, we report a detailed clinical description of a 10-year-old girl carrying a pathogenic interstitial 22q13.3 deletion encompassing only the first 17 exons of SHANK3.The clinical features displayed by the girl strongly suggested the diagnosis of dementia infantilis, described by Heller in 1908, also known as childhood disintegrative disorder.ConclusionOur present case confirms several observations according to which regression may be part of the clinical phenotype of SHANK3 haploinsufficiency. Therefore, we think it is crucial to look for mutations in the gene SHANK3 in patients diagnosed for childhood disintegrative disorder or any developmental disorder with a regressive pattern involving social and communicative skills as well as cognitive and instinctual functions, with onset around 3 years

The Recent Evolution of a Maternally-Inherited Endosymbiont of Ticks Led to the Emergence of the Q Fever Pathogen, Coxiella burnetii

International audienceQ fever is a highly infectious disease with a worldwide distribution. Its causative agent, the intracellular bacterium Coxiella burnetii, infects a variety of vertebrate species, including humans. Its evolutionary origin remains almost entirely unknown and uncertainty persists regarding the identity and lifestyle of its ancestors. A few tick species were recently found to harbor maternally-inherited Coxiella-like organisms engaged in symbiotic interactions, but their relationships to the Q fever pathogen remain unclear. Here, we extensively sampled ticks, identifying new and atypical Coxiella strains from 40 of 58 examined species, and used this data to infer the evolutionary processes leading to the emergence of C. burnetii. Phylogenetic analyses of multi-locus typing and whole-genome sequencing data revealed that Coxiella-like organisms represent an ancient and monophyletic group allied to ticks. Remarkably, all known C. burnetii strains originate within this group and are the descendants of a Coxiella-like progenitor hosted by ticks. Using both colony-reared and field-collected gravid females, we further establish the presence of highly efficient maternal transmission of these Coxiella-like organisms in four examined tick species, a pattern coherent with an endosymbiotic lifestyle. Our laboratory culture assays also showed that these Coxiella-like organisms were not amenable to culture in the vertebrate cell environment, suggesting different metabolic requirements compared to C. burnetii. Altogether, this corpus of data demonstrates that C. burnetii recently evolved from an inherited symbiont of ticks which succeeded in infecting vertebrate cells, likely by the acquisition of novel virulence factors

La financiarisation de la grande distribution: Restructuration de l’actionnariat et déclin économique du groupe Carrefour (1999-2013)

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Med Eng Phys

Biological scaffolds composed of extracellular matrix (ECM) derived from decellularised tissue are increasingly used in regenerative medicine. In this project, a flow perfusion bioreactor (the rotary cell culture system (RCCS), commercially available from Synthecon (Houston, TX)) is used in order to obtain some esophageal extracellular matrix. A theoretical mechanical characterisation of this experimental set-up is provided. Due to the combination of rotation and perfusion, some spiral Poiseuille flow is created inside the tubular esophagus. In a transverse section, a particle (or cell) experiences simultaneously gravitational, Archimedes, centrifugal, Coriolis, and drag forces. In a frame of reference rotating with angular velocity ω, the particle follows a periodic nearly circular path in the clockwise direction, associated with a very slow centrifugal drift towards the esophagus wall. It appears that moderate perfusion rate and rotation speed (ω < 20 rpm and Q < 30 ml/min) are appropriate experimental conditions for esophagus tissue engineering using the RCCS Synthecon bioreactor

MECHANICAL CHARACTERIZATION OF A ROTATING BIOREACTOR FOR TISSUE ENGINEERING

International audienceBiological scaffolds composed of extracellular matrix (ECM) derived from decellularized tissue are increasingly used in regenerative medicine [1]. Esophageal tissue engineering is a promising approach to create an esophageal substitute and improve clinical results in diseased esophageal treatment and surgery. Therefore, the need has arisen to develop decellularization techniques in order to obtain a clinical grade esophageal extracellular matrix. Decellularization should preserve the general structure and the biomechanical properties of the organ. Preservation of native ECM structure is essential to create a biocompatible scaffold that can be used for further cell seeding, differentiation and proliferation. In this study, decellularized scaffolds are prepared from pig esophagus using mild detergents, acids, and enzymes to remove animal cells, with the objective to provide scaffolds for recellularization with human stem cells, thus producing a new human esophagus [2]. For this purpose, a flow perfusion bioreactor is used: the rotary cell culture system (RCCS), commercially available from Synthecon (Houston, TX) [3]. This device allows liquid flow within the tubular esophagus, as well as a mechanical rotation in and around the tissue in two successive closed chambers. The aim of this paper is to provide an experimental and theoretical mechanical characterization of this flow device, in order to determine: i) the velocity fields, pressures, shear stresses in the fluid without suspended cells, ii) the forces that act on a suspended cell and determine its motion

Motion of a particle in a rotating bioreactor for tissue engineering

International audienceLe contexte de cette étude est la fabrication d'un substitut oesophagien par ingénierie tissulaire, à partir d'une matrice d'oesophage de porc décellularisé puis recellularisé avec des cellules humaines. Le bioréacteur choisi pour réaliser ces opérations est le RCCMax-dual (Synthecon), qui est adapté pour une géométrie tubulaire comme celle de l'oesophage. Ce dispositif permet de combiner un flux longitudinal du milieu circulant et un mouvement de rotation de l'ensemble du système de forme cylindrique. Les équations du mouvement sont résolues pour une particule qui se trouve donc à la fois entraînée par un écoulement de Poiseuille spiral et soumise aux forces de gravitation, d'Archimèdes, centrifuge, de Coriolis, et de frottement. Des conséquences pratiques sont déduites de cette analyse pour l'utilisation du RCCMax en ingénierie tissulaire, mais cette étude peut certainement être transposée à d'autres applications

Motion of a particle in a rotating bioreactor for tissue engineering

International audienceLe contexte de cette étude est la fabrication d'un substitut oesophagien par ingénierie tissulaire, à partir d'une matrice d'oesophage de porc décellularisé puis recellularisé avec des cellules humaines. Le bioréacteur choisi pour réaliser ces opérations est le RCCMax-dual (Synthecon), qui est adapté pour une géométrie tubulaire comme celle de l'oesophage. Ce dispositif permet de combiner un flux longitudinal du milieu circulant et un mouvement de rotation de l'ensemble du système de forme cylindrique. Les équations du mouvement sont résolues pour une particule qui se trouve donc à la fois entraînée par un écoulement de Poiseuille spiral et soumise aux forces de gravitation, d'Archimèdes, centrifuge, de Coriolis, et de frottement. Des conséquences pratiques sont déduites de cette analyse pour l'utilisation du RCCMax en ingénierie tissulaire, mais cette étude peut certainement être transposée à d'autres applications

Les crises de la grande distribution: Introduction du dossier

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Daily metabolism and hepatic balance studies of plasma cortisol and aldosterone in the preruminant calf

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