Spectroscopie RMN cérébrale pour l'étude du milieu intracellulaire in vivo (développements méthodologiques pour la diffusion à courtes échelles de temps et pour la mesure du pH en détection 31P)

La spectroscopie RMN est un moyen unique d évaluer l environnement cellulaire in vivo. En effet, les molécules observées sont exclusivement intracellulaires, et ont en général un rôle biochimique ainsi qu une compartimentation cellulaire spécifique. C est donc un outil potentiellement utile pour comprendre le fonctionnement des cellules dans leur environnement. Mon travail de thèse consistait à développer de nouvelles séquences en spectroscopie de diffusion et en spectroscopie du phosphore 31.Mon premier travail a été de développer une séquence de spectroscopie de diffusion à temps de diffusion ultra-court pour observer la diffusion anormale dans le cerveau de rat. L évolution de l ADC en fonction du temps de diffusion montre que le transport des métabolites dans le cerveau se fait essentiellement par diffusion aléatoire et que la contribution des transports actifs (s ils existent) est négligeable. La modélisation de ces données a mis en évidence que la spectroscopie de diffusion à court temps de diffusion était sensible à la viscosité du cytoplasme et à l encombrement à courte échelle. Cette technique a donc été choisie lors d une collaboration avec la firme Eli Lilly pour le suivi de souris transgéniques (rTg4510), modèle de taupathie. Les résultats préliminaires font apparaitre des différences significatives d ADC à un stade précoce de la neurodégénérescence (3 et 6 mois). La spectroscopie RMN du phosphore 31 permet d observer des métabolites directement impliqués dans le processus énergétique. Au cours de cette thèse, des séquences de localisation ont été développées pour pouvoir mesurer le pH intracellulaire dans le striatum de macaque. A terme, ces séquences seront utilisées pour évaluer l utilité potentielle du pH comme biomarqueur de la neurodégénérescence dans un modèle phénotypique de la maladie de Huntington chez le macaque.NMR spectroscopy is a unique modality to evaluate intracellular environment in vivo. Indeed observed molecules are specifically intracellular and generally have a biochemistry role and a specific cellular compartmentation. That could be a useful tool to understand cell functioning in their environment. My thesis work consisted in development of new sequence in both diffusion and phosphorus NMR spectroscopy.My first study was to develop a diffusion-weighted spectroscopy at ultra-short diffusion time to look at the anomalous diffusion in the rat brain. ADC evolution as a function of time shows that brain metabolites motion is mainly due to random diffusion and that active transport (if exist) are negligible. Data modeling evidences that diffusion at short diffusion time is sensitive to cytoplasm viscosity and short scale crowding. In collaboration with the pharmaceutical company, this technique was chosen to follow up transgenic mice (rTg4510), model of tau pathology. Preliminary results show significant differences of ADC at an early stage of neurodegenerescence (3 and 6 months).Phosphorus spectroscopy allows observation of metabolites directly implicated in energetic processes. During this thesis, localization sequences were developed to measure intracellular pH in the primate striatum. These sequences are supposed to be used to evaluate the potential of pH as a biomarker of neurodegenerescence in a phenotypic model of the Huntington disease in the non-human primate.PARIS11-SCD-Bib. électronique (914719901) / SudocSudocFranceF

Square cells in gravitational and capillary thermoconvection

The onset of square convective cells in fluid layers heated from below is investigated. Amplitude equations an deduced from the Boussinesq equations and a standard stability analysis is performed. Square cells are shown to be preferred when the instability is mainly capillarity driven. The influence of the Prandtl and Blot numbers are examined. At small Pr, the Plot number has not very much influence and squares are always observed for thin enough layers. in large Prandtl number fluids, Pi must be larger than the limiting value 0.28 for squares to be stable

ZIKA virus elicits P53 activation and genotoxic stress in human neural progenitors similar to mutations involved in severe forms of genetic microcephaly

International audienc

Magnetically controlled growing rod in early onset scoliosis: a 30-case multicenter study

PURPOSE: Preliminary results of magnetically controlled growing rods (MCGR) are encouraging. However, only short case series of MCGR for the treatment of early onset scoliosis (EOS) have been reported. Our aim was to evaluate its effectiveness and complications. METHODS: We report a 30-case retrospective, consecutive, multicenter series of MCGR. Effectiveness was judged upon: deformity correction and difficulties to achieve desired distraction. Secondary endpoints included complications and revision surgeries. RESULTS: Median age at surgery was 9.1 years (5-13). Mean follow-up was 18.4 months (12-33.9). Mean Cobb angle was 66° preoperatively and 44° at latest follow-up. MCGR has avoided an average of 2.03 scheduled surgical procedures per patient compared to traditional growing rod (GR). The intended total length gain was 40.1 mm per patient (5-140) and the total measured length gain was 21.9 mm (45.5% discrepancy). There were 24 complications: 7 proximal pull-outs of the hooks, 3 rod breakages, 6 failures of the lengthening of which 4 complete blockages and 2 complete blockages followed by backtracking, 1 proximal junctional kyphosis, 1 wound dehiscence, 1 superficial infection, 1 deep infection requiring implant removal, 1 pulmonary embolism, 1 pulmonary insufficiency, 1 secondary lumbar scoliosis, and 1 painful outpatient distraction. Eight patients had a gradual loss of effectiveness of distractions. There were 13 revision surgeries in 9 patients. CONCLUSIONS: MCGR provides satisfactory deformity correction and avoids repeated surgical procedures for lengthening. However, it has substantial complication rate. Although less frequent than in GR, the law of diminishing returns also applies to MCGR

Abstracts from the 50th European Society of Human Genetics Conference: Posters

International audienc

Risk factors for otitis media in children with special emphasis on the role of colonization with bacterial airway pathogens: the Generation R study

Acute otitis media is the most frequent diagnosis in children visiting physicians’ offices. Risk factors for otitis media have been widely studied. Yet, the correlation between bacterial carriage and the development of otitis media is not entirely clear. Our aim was to study in a population-based prospective cohort the risk factors for otitis media in the second year of life with special emphasis on the role of colonization with Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis. The study was embedded in the Generation R Study. Data on risk factors and doctor-diagnosed otitis media were obtained by midwives, hospital registries and postal questionnaires in the whole cohort (n = 7,295). Nasopharyngeal swabs were obtained at the age of 1.5, 6 and 14 months in the focus cohort (n = 1,079). Of these children, 2,515 (47.2%) suffered at least one period of otitis media in their second year of life. The occurrence of otitis media during the follow-up period in the first 6 months of life and between 6 and 12 months of age was associated with the risk of otitis media in the second year of life (aOR, 1.83 95% CI 1.24–2.71 and aOR 2.72, 95% CI 2.18–3.38, respectively). Having siblings was associated with an increased risk for otitis media in the second year of life (aOR 1.42, 95% CI 1.13–1.79). No associations were found between bacterial carriage in the first year of life and otitis media in the second year of life. In our study, otitis media in the first year of life is an independent risk factor for otitis media in the second year of life. Surprisingly, bacterial carriage in the first year of life did not add to this risk. Moreover, no association was observed between bacterial carriage in the first year of life and otitis in the second year of life

Strontium isotope evidence for Pre-Islamic cotton cultivation in Arabia

With a view to understanding the dynamics of ancient trade and agrobiodiversity, archaeobotanical remains provide a means of tracing the trajectories of certain agricultural commodities. A prime example is cotton in Arabia, a plant that is non-native but has been found in raw seed and processed textile form at Hegra and Dadan, in the region of al-ʿUlā, north-western Saudi Arabia—sites of critical importance given their role in the trans-Arabian trading routes during Antiquity. Here, we demonstrate that the measurement of strontium isotopes from pre-cleaned archaeological cotton is methodologically sound and is an informative addition to the study of ancient plant/textile provenance, in this case, putting forward evidence for local production of cotton in oasis agrosystems and possible external supply. The presence of locally-grown cotton at these sites from the late 1st c. BCE–mid 6th c. CE is significant as it demonstrates that cotton cultivation in Arabia was a Pre-Islamic socio-technical feat, while imported cotton highlights the dynamism of trade at that time

Spondyloenchondrodysplasia Due to Mutations in ACP5: A Comprehensive Survey

Purpose: Spondyloenchondrodysplasia is a rare immuno-osseous dysplasia caused by biallelic mutations in ACP5. We aimed to provide a survey of the skeletal, neurological and immune manifestations of this disease in a cohort of molecularly confirmed cases. Methods: We compiled clinical, genetic and serological data from a total of 26 patients from 18 pedigrees, all with biallelic ACP5 mutations. Results: We observed a variability in skeletal, neurological and immune phenotypes, which was sometimes marked even between affected siblings. In total, 22 of 26 patients manifested autoimmune disease, most frequently autoimmune thrombocytopenia and systemic lupus erythematosus. Four patients were considered to demonstrate no clinical autoimmune disease, although two were positive for autoantibodies. In the majority of patients tested we detected upregulated expression of interferon-stimulated genes (ISGs), in keeping with the autoimmune phenotype and the likely immune-regulatory function of the deficient protein tartrate resistant acid phosphatase (TRAP). Two mutation positive patients did not demonstrate an upregulation of ISGs, including one patient with significant autoimmune disease controlled by immunosuppressive therapy. Conclusions: Our data expand the known phenotype of SPENCD. We propose that the OMIM differentiation between spondyloenchondrodysplasia and spondyloenchondrodysplasia with immune dysregulation is no longer appropriate, since the molecular evidence that we provide suggests that these phenotypes represent a continuum of the same disorder. In addition, the absence of an interferon signature following immunomodulatory treatments in a patient with significant autoimmune disease may indicate a therapeutic response important for the immune manifestations of spondyloenchondrodysplasia