Slc2a10 knock-out mice deficient in ascorbic acid synthesis recapitulate aspects of arterial tortuosity syndrome and display mitochondrial respiration defects

Arterial tortuosity syndrome (ATS) is a recessively inherited connective tissue disorder, mainly characterized by tortuosity and aneurysm formation of the major arteries. ATS is caused by loss-of-function mutations in SLC2A10, encoding the facilitative glucose transporter GLUT10. Former studies implicated GLUT10 in the transport of dehydroascorbic acid, the oxidized form of ascorbic acid (AA). Mouse models carrying homozygous Slc2a10 missense mutations did not recapitulate the human phenotype. Since mice, in contrast to humans, are able to intracellularly synthesize AA, we generated a novel ATS mouse model, deficient for Slc2a10 as well as Gulo, which encodes for L-gulonolactone oxidase, an enzyme catalyzing the final step in AA biosynthesis in mouse. Gulo;Slc2a10 double knock-out mice showed mild phenotypic anomalies, which were absent in single knock-out controls. While Gulo;Slc2a10 double knock-out mice did not fully phenocopy human ATS, histological and immunocytochemical analysis revealed compromised extracellular matrix formation. Transforming growth factor beta signaling remained unaltered, while mitochondrial function was compromised in smooth muscle cells derived from Gulo;Slc2a10 double knock-out mice. Altogether, our data add evidence that ATS is an ascorbate compartmentalization disorder, but additional factors underlying the observed phenotype in humans remain to be determined

Development and characterization of innovative and ecological surface materials for security and comfort in automotive applications

Les polyoléfines thermoplastiques (TPO) sont des matériaux issus du mélange entre le polypropylène, le polyéthylène et des élastomères éthylène-propylène. Ils sont utilisés notamment dans le domaine automobile pour la fabrication des pare-chocs et le revêtement de surface des pièces intérieures comme le tableau de bord. Pour cette dernière application, des feuilles de TPO grainées sont thermoformées afin de s’adapter aux contours des pièces. Lors de cette mise en forme, le grain de la feuille est déformé et son épaisseur réduite, diminuant la qualité perçue du revêtement. Le traitement du TPO par bombardement électronique (EB), réalisé lors de ce travail de thèse, est une technique de choix afin de modifier les propriétés physico-chimiques du polymère et de potentiellement améliorer le thermoformage des feuilles TPO. Une étude préliminaire a été effectuée en irradiant par EB une formulation TPO commerciale. Une altération des propriétés mécaniques et thermiques est causée par le traitement radiatif. Une amélioration de la thermoformabilité du TPO est également mise en évidence. L’effet de l’EB est néanmoins limité et nécessite d’adapter la formulation. Deux voies ont été envisagées dans la suite de cette étude. Pour la première, des formulations TPO contenant des copolymères triblocs ont été développées. Dans la seconde, des monomères réactifs ont été ajoutés aux TPO. L’effet du traitement radiatif par EB sur ces formulations est ensuite caractérisé par diverses méthodes (analyses enthalpiques différentielles et thermogravimétriques, traction uniaxiale) et des essais de thermoformage. Des résultats intéressants ont été obtenus en vue d'applications concrètes.Thermoplastic olefins (TPO) are polymeric materials produce by blending polypropylene, polyethylene and their copolymers. They are used especially in automotive industry to produce bumpers or as skin layer for interior parts such as dashboard. For this application, the shape of the part is given by thermoforming a grained TPO foil. During the process, the thickness of the foil decrease and the grain can be deformed. Thus the user-perceived quality of the final product doesn’t match with customer’s expectation. The treatment of TPO by electron beam (EB) was chosen in this work to modify some physic-chemical properties and potentially improve the thermoforming of TPO’s foil. A preliminary study concerns the irradiation of a commercial TPO mixture. Changes of mechanical and thermal properties are highlighted after treatment. The thermoformability of foil is improved too. However, the effect of EB on the commercial material is restricted by the degradation of polypropylene and some new formulation need to be developed. For this purpose, two different ways are investigated. In the first formulation, TPO is blended with some concentration of triblock copolymer. In the second, reactive monomers are added in the material. These formulations are irradiated by EB and the effect of the treatment is characterized by different methods (differential scanning calorimetry, thermogravimetric analysis, tensile test…). Changes of thermoformability are also evaluated for the developed materials

Novel interpenetrating polymer network composed of poly(butyl acrylates) and poly(ethyl-hexyl acrylate)

International audienceNovel full acrylic interpenetrating polymer networks (IPNs) made up of thePoly Ethyl- Hexyl Acrylate (PEHA) and Poly Butyl-Acrylate (PABu) networkswith various crosslinking ratios were characterized by means of Infraredspectroscopy, swelling, DSC and TGA techniques. The systems are preparedvia photo-polymerization by UV-curing of monomers in the presence of adifunctional crosslinker and a photo-initiator. The physical properties of theIPNs are mainly influenced by the quantity of the monomer present in theIPNs and increasing the crosslinker prevents formation of unreactedoligomers inside the IPNs. Surprisingly, the IPNs with 0.5% crosslinker doesnot present any phase separation

Elaboration of new modified electrodes (MEs) by electropolymerization of Cu(II)-Schiff base complexes bearing pyrrole moieties: Application in electroreduction of acetophenone and carbon dioxide

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Sensorimotor vs. motor upper limb therapy for patients with motor and somatosensory deficits : a randomized controlled trial in the early rehabilitation phase after stroke

Background: Somatosensory function plays an important role in motor learning. More than half of the stroke patients have somatosensory impairments in the upper limb, which could hamper recovery. Question: Is sensorimotor upper limb (UL) therapy of more benefit for motor and somatosensory outcome than motor therapy? Design: Randomized assessor- blinded multicenter controlled trial with block randomization stratified for neglect, severity of motor impairment, and type of stroke. Participants: 40 first-ever stroke patients with UL sensorimotor impairments admitted to the rehabilitation center. Intervention: Both groups received 16 h of additional therapy over 4 weeks consisting of sensorimotor (N = 22) or motor (N = 18) UL therapy. Outcome measures: Action Research Arm test (ARAT) as primary outcome, and other motor and somatosensory measures were assessed at baseline, post-intervention and after 4 weeks follow-up. Results: No significant between-group differences were found for change scores in ARAT or any somatosensory measure between the three time points. For UL impairment (Fugl-Meyer assessment), a significant greater improvement was found for the motor group compared to the sensorimotor group from baseline to post-intervention [mean (SD) improvement 14.65 (2.19) vs. 5.99 (2.06); p = 0.01] and from baseline to follow-up [17.38 (2.37) vs. 6.75 (2.29); p = 0.003]. Conclusion: UL motor therapy may improve motor impairment more than UL sensorimotor therapy in patients with sensorimotor impairments in the early rehabilitation phase post stroke. For these patients, integrated sensorimotor therapy may not improve somatosensory function and may be less effective for motor recovery

Mutation and Methylation Analysis of Circulating Tumor DNA Can Be Used for Follow-up of Metastatic Colorectal Cancer Patients

International audienceBACKGROUND:Targeted therapies, although contributing to survival improvement in metastatic colorectal cancer (mCRC), are expensive and may cause adverse effects. Therefore, confirming that patients are responding to these therapies is extremely important. Currently, follow-up is performed using radiographic evaluation, which has its limitations. Liquid biopsies, reflecting real-time tumor characteristics, hold great potential in monitoring tumor disease.PATIENTS AND METHODS:Blood samples were collected at different time points during treatment of 24 mCRC patients. Mutation and NPY methylation picoliter droplet-based digital PCR (ddPCR) assays were performed on circulating DNA to investigate whether these assays can be used for disease monitoring.RESULTS:The results of the mutation and methylation assays were correlated with each other and corresponded with the results of radiographic evaluation. There was a steep decrease in circulating tumor DNA levels immediately after treatment initiation. Furthermore, circulating tumor DNA levels were increased in progressive samples and were undetectable in patients undergoing curative surgery.CONCLUSION:This prospective study showed that tumor-specific mutation and NPY methylation ddPCR assays performed on circulating DNA can be used for the follow-up of mCRC patients during treatment and could complement current follow-up methods. The analysis of NPY methylation is promising, as it has the additional advantage that no prior knowledge of tumor mutations is needed