Développement des compétences et des cerlces sociaux à l'adolescence : conséquances des interactions médiatisées par ordinateur

Ce travail porte sur le développement des compétences sociales et des cercles sociaux à l'adolescence. Il s'intéresse plus particulièrement à l'effet au cours du temps que peuvent avoir les nouveaux moyens de communication électronique (MCE) sur ces deux aspects de la socialisation. Trois parties principales se dégagent de ce travail. La première partie présente le développement d'un outil multidimensionnel destiné à l'évaluation des compétences sociales et permettant de les distinguer en fonction du contexte d'interaction (online vs. offline). La seconde partie porte sur la comparaison des compétences sociales et de la taille du cercle social de 329 adolescents de 7e et de 8e année primaire, en fonction de leur utilisation, ou non, des MCE. Elle met en évidence que ces deux aspects diffèrent de manière statistiquement significative entre les deux groupes, en faveur des utilisateurs de MCE. La troisième partie se centre sur l'utilisation de différents MCE et sur les effets différentiels qu'ils peuvent avoir au cours du temps sur ces deux aspects de la socialisation. Les analyses des données longitudinales mettent en évidence que l'utilisation de sites de réseaux sociaux (SRS) est particulièrement susceptible d'améliorer les compétences sociales et d'augmenter la taille du cercle social. Un modèle dans lequel les compétences sociales jouent un rôle de médiateur entre l'utilisation de SRS et la taille du cercle social est finalement postulé. - This work's topic concerns the development of social skills and social network size during adolescence. It examines more particularly the effects that new online communication media (OCM) may have on these two aspects of adolescent socialization. It is subdivided in three distinct parts. The first part presents the development of a multidimensional tool designed to assess social skills in two different contexts of interaction (online vs. offline). The second part compares the social skills and social network size of 329 adolescents depending on their use, or not, of OCM. It highlights significant differences on these two aspects between users and non-users, in favor of OCM users. The third part focuses on the differential effects that six OCM may have over time on these two aspects of socialization. Longitudinal data analyses highlight that the use of social network sites (SNS) is particularly likely to improve social skills and to increase social network size. A model in which social skills mediate the relationship between SNS use and social network size is finally postulated.

Increased body fat is independently and negatively related with cardiorespiratory fitness levels in children and adolescents with normal weight.

Body mass index (BMI) is related with cardiorespiratory fitness (CRF), but less is known regarding the combined relationships between BMI and body fat (BF) on CRF. Cross-sectional study included 2361 girls and 2328 boys aged 10–18 years living in the area of Lisbon, Portugal. BMI was calculated by measuring height and weight, and obesity was assessed by international criteria. BF was assessed by bioimpedance. CRF was assessed by the 20-m shuttle run and the participants were classified as normal-to-high or low-CRF level according to Fitness gram criterion-referenced standards. The prevalence of low CRF was 47 and 39% in girls and boys, respectively. The corresponding values for the prevalence of obesity were 4.8 and 5.6% (not significant) and of excess BF of 12.1 and 25.1% (P <0.001), respectively. In both sexes, BMI and BF were inversely related with CRF: r = – 0.53 and – 0.45 for BMI and % BF, respectively, in boys and the corresponding values in girls were – 0.50 and – 0.33 (all P <0.01). When compared with a participant with normal BMI and BF, the odds ratios (95% confidence interval) for low CRF were 1.94 (1.46–2.58) for a participant with normal BMI and high BF, and 6.19 (5.02–7.63) for a participant with high BMI and high BF. The prevalence of low-CRF levels is high in Portuguese youths. BF negatively influences CRF levels among children/adolescents with normal BMI.

Epidermal differentiation and carcinogenesis

Summary Skin, and more precisely the epidermis, plays a crucial role in our survival since it constitutes our first line of defense against our environment. A subtle equilibrium between proliferation and differentiation of keratinocytes, the main epidermal cell type, provides a continous self-renewal of the epidermis, maintaining the integrity of this protective barrier. It is now well established that pertubation of the normal balance between proliferation and differentiation can induce development of several diseases including cancer. The aim of my thesis was first to characterize new genes involved in the differentiation process of keratinocytes and the formation of the epidermis. We show that cornulin, encoded by the c1orf10 gene, is a new marker of epidermal differentiation, mainly expressed in the suprabasal layers of the epidermis. Structurally, cornulin belongs to the "fused genes" protein family and contains a functional calcium-binding domain as well as two repeated sequences of 60 amino acids, the function of which remain unknown. The second part of my work aimed to identify new proteins interacting with CYLD. When mutated, CYLD is responsible for cylindromatosis, a predisposition to benign tumors of skin appendages mainly located on the scalp. CYLD is implicated in the NF-κB signalling pathway. We have identified HBO1 and p30, two nuclear proteins, as potential CYLD partners. Since CYLD was described as a negative regulator of NF-icB-mediated transcription, we have tested the putative effect of HBO1 and p30 on the regulation of this signalling pathway. We have shown that only HBO1 is able to inhibit NF-κB-mediated transactivation. The mechanism of action of HBO1 is still under investigation but our results suggest that an unknown cofactor is involved in this process. Résumé La peau est cruciale à notre survie car elle est notre première ligne de défense contre notre environnement. L'épiderme qui forme cette barrière protectrice entre le corps et l'environnement extérieur est continuellement renouvelé suite aux agressions physiques, chimiques et biologiques répétées qu'il subit. Le but de ce renouvellement étant de garantir l'intégrité de cette barrière. Le keratinocyte est le principal type cellulaire trouvé dans l'épiderme. La formation d'une barrière active dépend essentiellement de la faculté des kératinocytes à proliférer et à se différencier. Il est aujourd'hui admis que tout déséquilibre entre l'activité de prolifération et de différenciation des kératinocytes est la cause du développement de plusieurs maladies, dont certains cancers. Le but de ce travail de thèse était, dans un premier temps d'identifier ou de caractériser de nouveaux gènes impliqués dans le processus de différenciation afin de mieux comprendre la formation de l'épiderme. Noús avons ainsi démontré que la cornulin, produit du gène c1orf10, est un nouveau marqueur de la différenciation épidermique, principalement exprimé dans les couches suprabasales de l'épiderme. D'un point de vue structural, nous avons montré que cette protéine appartient à la famille des « fused gene » et qu'elle possède un domaine de liaison au calcium qui est fonctionnel et deux séquences répétées de 60 acides aminés dont la fonction est encore inconnue. La seconde partie de cette thèse était dédiée à l'étude de la cylindromatose, une prédisposition génétique à la formation de tumeurs bénignes, principalement localisées sur la tête et due à des mutations du gène CYLD. Nous avons cherché de nouvelles protéines qui interagissent avec CYLD afin de mieux caractériser les voies de signalisation impliquées dans le développement de la maladie. Nous avons ainsi identifiés deux nouveaux partenaires potentiels de CYLD ; HBO1 et p30 CYLD ayant été décrit comme un régulateur négatif de la transcription médiée par NF-κB; nous avons testé l'implication de HBO1 et p30 au niveau de cette activité transcriptionnelle. Nous montrons que seul HBO1 est capable d'inhiber la transactivation d'un gène rapporteur régulé par NF-κB. Le mécanisme d'action de HBO1 n'est pas encore connu, néanmoins nos résultats suggèrent l'intervention d'un cofacteur qui reste à déterminer.

Tc-99m-MAA SPECT-derived tumor-to-normal liver ratios for partition model dosimetry in selective internal radiation therapy (SIRT)

Aim: When planning SIRT using 90Y microspheres, the partition model is used to refine the activity calculated by the body surface area (BSA) method to potentially improve the safety and efficacy of treatment. For this partition model dosimetry, accurate determination of mean tumor-to-normal liver ratio (TNR) is critical since it directly impacts absorbed dose estimates. This work aimed at developing and assessing a reliable methodology for the calculation of 99mTc-MAA SPECT/CT-derived TNR ratios based on phantom studies. Materials and methods: IQ NEMA (6 hot spheres) and Kyoto liver phantoms with different hot/background activity concentration ratios were imaged on a SPECT/CT (GE Infinia Hawkeye 4). For each reconstruction with the IQ phantom, TNR quantification was assessed in terms of relative recovery coefficients (RC) and image noise was evaluated in terms of coefficient of variation (COV) in the filled background. RCs were compared using OSEM with Hann, Butterworth and Gaussian filters, as well as FBP reconstruction algorithms. Regarding OSEM, RCs were assessed by varying different parameters independently, such as the number of iterations (i) and subsets (s) and the cut-off frequency of the filter (fc). The influence of the attenuation and diffusion corrections was also investigated. Furthermore, both 2D-ROIs and 3D-VOIs contouring were compared. For this purpose, dedicated Matlab© routines were developed in-house for automatic 2D-ROI/3D-VOI determination to reduce intra-user and intra-slice variability. Best reconstruction parameters and RCs obtained with the IQ phantom were used to recover corrected TNR in case of the Kyoto phantom for arbitrary hot-lesion size. In addition, we computed TNR volume histograms to better assess uptake heterogeneityResults: The highest RCs were obtained with OSEM (i=2, s=10) coupled with the Butterworth filter (fc=0.8). Indeed, we observed a global 20% RC improvement over other OSEM settings and a 50% increase as compared to the best FBP reconstruction. In any case, both attenuation and diffusion corrections must be applied, thus improving RC while preserving good image noise (COV<10%). Both 2D-ROI and 3D-VOI analysis lead to similar results. Nevertheless, we recommend using 3D-VOI since tumor uptake regions are intrinsically 3D. RC-corrected TNR values lie within 17% around the true value, substantially improving the evaluation of small volume (<15 mL) regions. Conclusions: This study reports the multi-parameter optimization of 99mTc MAA SPECT/CT images reconstruction in planning 90Y dosimetry for SIRT. In phantoms, accurate quantification of TNR was obtained using OSEM coupled with Butterworth and RC correction.

Pharmacodynamic and humoral effects of single intravenous doses of captopril in normal subjects.

The blood pressure, heart rate and humoral responses to single intravenous doses of the angiotensin converting enzyme inhibitor captopril were evaluated in 5 volunteers on a free salt intake. Each subject was given at one-week intervals a 1, 5 and 25 mg intravenous dose of captopril as well as the vehicle of captopril. The study was conducted in a single-blind fashion and the order of treatment phases was randomized. Captopril was found to inhibit the renin-angiotensin system in a dose-dependent fashion. A fall in circulating angiotensin II was observed with doses of 1 and 5 mg. Plasma angiotensin II was not detectable 15 min after the 25 mg dose. Acute inhibition of angiotensin converting enzyme with intravenous captopril had no effect on blood pressure and heart rate.

Genetics of normal and pathological sleep in humans.

The complexity of sleep-wake regulation, in addition to the many environmental influences, includes genetic predisposing factors, which begin to be discovered. Most of the current progress in the study of sleep genetics comes from animal models (dogs, mice, and drosophila). Multiple approaches using both animal models and different genetic techniques are needed to follow the segregation and ultimately to identify 'sleep genes' and molecular bases of sleep disorders. Recent progress in molecular genetics and the development of detailed human genome map have already led to the identification of genetic factors in several complex disorders. Only a few genes are known for which a mutation causes a sleep disorder. However, single gene disorders are rare and most common disorders are complex in terms of their genetic susceptibility, environmental factors, gene-gene, and gene-environment interactions. We review here the current progress in the genetics of normal and pathological sleep and suggest a few future perspectives.

Transition écologique, plutôt que développement durable. Entretien

Entretien

RNA interference against aquaporin-4 decreases the apparent diffusion coefficient in the normal brain

Aim: Diffusion weighted magnetic resonance imaging (MRI) is now widely used in human brain diagnosis.1 To date molecular mechanisms underlying changes in Apparent Diffusion Coefficient (ADC) signals remain poorly understood. AQP4, localized to astrocytes, is one of the most highly expressed cerebral AQPs.2 AQP4 is involved in water movement within the cell membrane of cultured astrocytes.3 We hypothesize that AQP4 contributes to water diffusion and underlying ADC values in normal brain. Methods: We used an RNA interference (RNAi) protocol in vivo, to acutely knockdown expression of AQP4 in rat brain and to determine whether this was associated with changes in brain ADC values using MRI protocols as previously described.4 RNAi was performed using specific small interference RNA (siRNA) against AQP4 (siAQP4) and a non-targeted-siRNA (siGLO) as a control. The specificity and efficiency of the siAQP4 were first tested in vitro in astrocyte and hippocampal slice cultures. In vivo, siRNAs were injected into the rat cortex 3d prior to MRI acquisition and AQP4 was assessed by western blot (n=4) and immunohistochemistry (n=6). Histology was performed on adjacent slices. Results: siAQP4 application on primary astrocyte cultures induced a 76% decrease in AQP4 expression after 4 days. In hippocampal slice cultures; we also found a significant decrease in AQP4 expression in astrocytes after siAQP4. In vivo, injection of non-targeted siRNA (siGLO) tagged with CY3 allowed us to show that GFAP positive cells (astrocytes) were positively stained with CY3-siGLO, showing efficient transfection. Western blot and immunohistochemical analysis showed that siAQP4 induced a ~30% decrease in AQP4 expression without modification of tissue properties or cell death. After siAQP4 treatment, a significant decrease in ADC values (~50%) were observed without altered of T2 values. Conclusions: Together these results suggest that AQP4 reduces water diffusion through the astrocytic plasma membrane and decreases ADC values. Our findings demonstrate for the first time that astrocytic AQP4 contributes significantly to brain water diffusion and ADC values in normal brain. These results open new avenues to interpretation of ADC values under normal physiological conditions and in acute and chronic brain injuries.