De novo TBR1 variants cause a neurocognitive phenotype with ID and autistic traits:report of 25 new individuals and review of the literature

TBR1, a T-box transcription factor expressed in the cerebral cortex, regulates the expression of several candidate genes for autism spectrum disorders (ASD). Although TBR1 has been reported as a high-confidence risk gene for ASD and intellectual disability (ID) in functional and clinical reports since 2011, TBR1 has only recently been recorded as a human disease gene in the OMIM database. Currently, the neurodevelopmental disorders and structural brain anomalies associated with TBR1 variants are not well characterized. Through international data sharing, we collected data from 25 unreported individuals and compared them with data from the literature. We evaluated structural brain anomalies in seven individuals by analysis of MRI images, and compared these with anomalies observed in TBR1 mutant mice. The phenotype included ID in all individuals, associated to autistic traits in 76% of them. No recognizable facial phenotype could be identified. MRI analysis revealed a reduction of the anterior commissure and suggested new features including dysplastic hippocampus and subtle neocortical dysgenesis. This report supports the role of TBR1 in ID associated with autistic traits and suggests new structural brain malformations in humans. We hope this work will help geneticists to interpret TBR1 variants and diagnose ASD probands

Clinical spectrum of MTOR-related hypomelanosis of Ito with neurodevelopmental abnormalities.

PURPOSE: Hypomelanosis of Ito (HI) is a skin marker of somatic mosaicism. Mosaic MTOR pathogenic variants have been reported in HI with brain overgrowth. We sought to delineate further the pigmentary skin phenotype and clinical spectrum of neurodevelopmental manifestations of MTOR-related HI. METHODS: From two cohorts totaling 71 patients with pigmentary mosaicism, we identified 14 patients with Blaschko-linear and one with flag-like pigmentation abnormalities, psychomotor impairment or seizures, and a postzygotic MTOR variant in skin. Patient records, including brain magnetic resonance image (MRI) were reviewed. Immunostaining (n = 3) for melanocyte markers and ultrastructural studies (n = 2) were performed on skin biopsies. RESULTS: MTOR variants were present in skin, but absent from blood in half of cases. In a patient (p.[Glu2419Lys] variant), phosphorylation of p70S6K was constitutively increased. In hypopigmented skin of two patients, we found a decrease in stage 4 melanosomes in melanocytes and keratinocytes. Most patients (80%) had macrocephaly or (hemi)megalencephaly on MRI. CONCLUSION: MTOR-related HI is a recognizable neurocutaneous phenotype of patterned dyspigmentation, epilepsy, intellectual deficiency, and brain overgrowth, and a distinct subtype of hypomelanosis related to somatic mosaicism. Hypopigmentation may be due to a defect in melanogenesis, through mTORC1 activation, similar to hypochromic patches in tuberous sclerosis complex

CFD-guided patterning of tubular ceramic membrane surface by stereolithography: Optimizing morphology at the mesoscale for improved hydrodynamic control of membrane fouling

International audienc

Manufacturing of Large Size and Highly Transparent Nd:YAG Ceramics by Pressure Slip-Casting and Post-Sintering by HIP: An Experimental and Simulation Study

International audienceThis study reports the fabrication of Nd:YAG (i.e., Neodymium-doped Yttrium Aluminum Garnet: Y3-xNdxAl5O12) transparent ceramics of a large size by the pressure slip-casting forming technique. Colloidal suspensions of primary oxides (i.e., Y2O3, Al2O3, Nd2O3, and SiO2 used as sintering aid) were cast under pressure through a porous membrane. Cakes with a good microstructural homogeneity and mean pore diameter of 90 nm were obtained. Modeling of the pressure slip-casting process at the millimetric to centimetric scale based on a computational fluid dynamics simulation showed good agreement with experimental results in terms of the casting kinetics (i.e., cake thickness and fluid flow as a function of time) and cake permeability. As a result, it was possible to better manage pressure casting parameters in order to obtain large size and homogeneous green parts. Finally, transparent Nd:YAG ceramics sintered by vacuum sintering, followed by post-sintering treatment by Hot Isostatic Pressing (HIP), demonstrated laser slope efficiency (51.7%) and optical-to-optical efficiency (44%) with 130 mJ of output laser energy at 1064 nm equivalent to commercial single crystals

Towards building of a “numerical ham” for simulating proteolysis and salt and water transfers during the dry-cured ham elaboration process

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Time-course evolution of protein degradation velocity in pork meat samples: integration in a model simulating dry-cured ham manufacture

National audienc

MRI assessment of deformation and water loss during meat heating

The understanding and control of structural and physical changes in meat during cooking is essential for both meat industries and consumers. Magnetic resonance imaging (MRI) offers a non-invasive method for the local and dynamic characterisation of certain properties and structures of a sample. The aim of this work was to demonstrate the feasibility of using MRI in situ during the cooking of meat, and in particular imaging of the connective tissue to monitor deformation in the range 20-75 °C. The associated moisture loss was also estimated. Simulations of the temperature time course during cooking were carried out to relate deformation to sample temperature. The results showed that shrinkage began at 42 °C and accelerated from 54 °C. Migration of water from inside the fibres towards the interfascicular space appeared from 40°C and increased from 52 °C. These findings are consistent with those obtained by other, destructive and (or) non-localised methods. They will be used to determine deformation fields

Heat-induced volatiles and odour-active compounds in a model cheese

International audienceThe aim of this work was to identify and characterize the volatile compounds formed during the cooking of a model cheese. Particular attention was paid to the generation of the odour-active volatile fraction, which can contribute to the sensory characteristics of cheeses. To this end we used various analytical methods including two-dimensional gas chromatography coupled with time-of-flight mass spectrometry and chromatography—olfactometry. The changes observed in the volatile fraction enabled us to follow several markers of lipid oxidation, caramelization and Maillard reaction mechanisms during cooking. Maltol and furaneol, though present in only trace amounts, gave rise to "overcooked" odour defects in the cheese matrices

Qualité des fromages fermiers lactiques : locaux et maitrise de l’affinage (LACTAFF)

Le programme LACTAFF (2012 – 2015) a eu pour objectif d’améliorer la maîtrise de l’affinage des fromages fermiers lactiques, technologie la plus couramment utilisée à la ferme, en fournissant des outils et des références aux producteurs et aux techniciens qui les accompagnent. Des enquêtes menées dans 49 fermes des 6 principales régions produisant ce type de fromage ont permis de caractériser la grande diversité des fromages fabriqués, des locaux, des équipements et des pratiques et d’établir des liens entre les grandes catégories de fromages et les pratiques, locaux et conditions d’ambiance. Par ailleurs, au laboratoire et en fromageries expérimentales, le rôle clé de l’hygrométrie a été quantifié en affinage, ainsi qu’au séchage où la vitesse d’air joue un rôle encore plus important. Les effets des paramètres d’ambiance sur la composition physico-chimique et les caractéristiques sensorielles des fromages ont été quantifiés pour un type de fromage donné.The « LACTAFF » program (2012-2015) aimed at improving the control of goat lactic farmhouse cheese ripening, a technology frequently used by farmers, by producing tools and references for producers and the technicians guiding them. Surveys conducted in 49 farms in the 6 main regions producing this kind of cheeses allowed to characterize the great diversity of cheeses, premises, equipment and practices, and to link cheese categories with practices, premises characteristics and air production conditions. In laboratory and experimental dairies, the key role of humidity was quantified during ripening and during drying, in which air speed is even more important. Atmospheric parameters effects on cheeses physicochemical composition and sensory characteristics were quantified for one type of cheeses. Specialist experience of cheese technology, premises design and climate control equipment and technician experience were capitalized at the same time. This project led to the writing of technical documents available online and a book about lactic farmhouse cheeses ripening