Fetal programming of pulmonary vascular dysfunction in mice: role of epigenetic mechanisms.

Insults during the fetal period predispose the offspring to systemic cardiovascular disease, but little is known about the pulmonary circulation and the underlying mechanisms. Maternal undernutrition during pregnancy may represent a model to investigate underlying mechanisms, because it is associated with systemic vascular dysfunction in the offspring in animals and humans. In rats, restrictive diet during pregnancy (RDP) increases oxidative stress in the placenta. Oxygen species are known to induce epigenetic alterations and may cross the placental barrier. We hypothesized that RDP in mice induces pulmonary vascular dysfunction in the offspring that is related to an epigenetic mechanism. To test this hypothesis, we assessed pulmonary vascular function and lung DNA methylation in offspring of RDP and in control mice at the end of a 2-wk exposure to hypoxia. We found that endothelium-dependent pulmonary artery vasodilation in vitro was impaired and hypoxia-induced pulmonary hypertension and right ventricular hypertrophy in vivo were exaggerated in offspring of RDP. This pulmonary vascular dysfunction was associated with altered lung DNA methylation. Administration of the histone deacetylase inhibitors butyrate and trichostatin A to offspring of RDP normalized pulmonary DNA methylation and vascular function. Finally, administration of the nitroxide Tempol to the mother during RDP prevented vascular dysfunction and dysmethylation in the offspring. These findings demonstrate that in mice undernutrition during gestation induces pulmonary vascular dysfunction in the offspring by an epigenetic mechanism. A similar mechanism may be involved in the fetal programming of vascular dysfunction in humans.

Evaluation and comparison of current fetal ultrasound image segmentation methods for biometric measurements: a grand challenge.

This paper presents the evaluation results of the methods submitted to Challenge US: Biometric Measurements from Fetal Ultrasound Images, a segmentation challenge held at the IEEE International Symposium on Biomedical Imaging 2012. The challenge was set to compare and evaluate current fetal ultrasound image segmentation methods. It consisted of automatically segmenting fetal anatomical structures to measure standard obstetric biometric parameters, from 2D fetal ultrasound images taken on fetuses at different gestational ages (21 weeks, 28 weeks, and 33 weeks) and with varying image quality to reflect data encountered in real clinical environments. Four independent sub-challenges were proposed, according to the objects of interest measured in clinical practice: abdomen, head, femur, and whole fetus. Five teams participated in the head sub-challenge and two teams in the femur sub-challenge, including one team who tackled both. Nobody attempted the abdomen and whole fetus sub-challenges. The challenge goals were two-fold and the participants were asked to submit the segmentation results as well as the measurements derived from the segmented objects. Extensive quantitative (region-based, distance-based, and Bland-Altman measurements) and qualitative evaluation was performed to compare the results from a representative selection of current methods submitted to the challenge. Several experts (three for the head sub-challenge and two for the femur sub-challenge), with different degrees of expertise, manually delineated the objects of interest to define the ground truth used within the evaluation framework. For the head sub-challenge, several groups produced results that could be potentially used in clinical settings, with comparable performance to manual delineations. The femur sub-challenge had inferior performance to the head sub-challenge due to the fact that it is a harder segmentation problem and that the techniques presented relied more on the femur's appearance.

Perception of cardiovascular risk and comparison with actual cardiovascular risk.

BACKGROUND: Current guidelines recommend treating patients according to their absolute cardiovascular disease (CVD) risk. We examined perception of CVD risk among adults and how it can be compared with actual CVD risk. METHODS: The perception of CVD risk was assessed by two questions asking about participants' 'risk to get a heart attack or a stroke over the next 10 years' using semiquantitative and quantitative answers in a population-based survey of 816 individuals aged 40-64 years in the Seychelles (African region). Actual CVD risk was calculated using a standard risk prediction score and 24% of adults aged 40-64 years had elevated risk. RESULTS: Only 59% of individuals could give an estimate of perceived CVD risk based on the semiquantitative question and 31% based on the quantitative question. Reporting a perceived CVD risk was strongly associated with high socio-economic status (SES; odds ratio = 9). Among individuals who reported a perceived CVD risk, 48% overestimated their perceived risk versus their actual risk. Reporting a high perceived CVD risk was associated with treatment for CVD risk factors, older age, low SES, and overweight. Reporting a low perceived CVD risk was associated with male sex, younger age, education, normal BMI, and leisure time exercise. CONCLUSION: Only half of the individuals could provide an estimate of their perceived CVD risk, and this perception was strongly associated with SES. Individuals under treatment perceived higher CVD risk than nontreated individuals. Further studies should determine how risk-related information can be better conveyed to individuals as a means to improve adherence to healthy lifestyles and/or treatment.

Thymus-independent generation of NK1+ T cells in vitro from fetal liver precursors.

NK1.1+TCR alpha beta+ (NK1+) T cells are an unusual subset of mouse TCR alpha beta+ cells found primarily in adult thymus and liver. In contrast to conventional TCR alpha beta+ cells, NK1+ T cells have a TCR repertoire that is highly skewed to V alpha14 and to Vbeta8, -7, and -2. The developmental origin and ligand specificity of NK1+ T cells are controversial. We show here that NK1+ T cells with a typically biased V alpha and V beta repertoire develop in cytokine-supplemented suspension cultures of fetal liver established from either normal or athymic mice. Furthermore, NK1+ T cell development in fetal liver cultures is abrogated in beta2m-deficient mice (which lack MHC class I and other related molecules) and can be partially inhibited by the presence of anti-CD1 mAbs. Moreover, mixing experiments indicate that recombination-deficient SCID fetal liver cells can reconstitute NK1+ T cell development in beta2m-deficient fetal liver cultures. Collectively, our data demonstrate that NK1+ T cells can develop extrathymically from fetal liver precursors and that a beta2m-associated ligand (putatively CD1) present on nonlymphoid cells is essential for their positive selection and/or expansion.

Justification du système économique et perception du travail en groupe

L'étude classique des attributions de responsabilité instiguée par Heider en psychologie sociale s'est principalement bornée à aborder ce processus psychosocial dans une perspective individualiste qui se cantonne aux niveaux intra-individuel et interpersonnel (selon la distinction opérée par Doise). Les réflexions et les travaux empiriques présentés dans cette thèse ont deux objectifs. Dans un premier temps, il s?agit d'élargir cette perspective aux autres niveaux sociologique et idéologique (en faisant notamment recours à l'approche des attributions sociales et aux propositions de Fauconnet sur les règles de responsabilité). Deuxièmement, il s?agit d'éprouver la pertinence d'une telle approche dans un contexte particulier : celui du travail en groupe dont la nature des rapports sociaux qui y étaient présentés ont été manipulés à l'aide de scénarii chez des étudiant-e-s de l?Université de Lausanne. L?objectif principal de cette thèse est donc de tester un modèle d?ancrage des attributions de responsabilité qui permette de souligner les dynamiques représentationnelles sous-jacentes en termes de légitimation ou de remise en cause de l?organisation des groupes. Dans l?ensemble les résultats indiquent que si la nature des rapports sociaux (re)présentés dans un groupe sont de puissants déterminants de la manière de légitimer ou de remettre en cause l?organisation des groupes, le niveau individuel d'adhésion à des croyances idéologiques dominantes, comme la justification du système économique, représente un modérateur des prises de position des répondant-e-s interrogé-e-s. De plus, il semble que ces processus évoluent dans le temps, faisant ainsi apparaître l'existence de phénomènes de socialisation relativement plus complexes que ne le laissent entendre les recherches actuellement effectuées dans ce domaine. En effet, si des connaissances idéologiques sur le monde sont acquises dans les filières universitaires et n?interviennent pas toujours dans les processus de formation des représentations du travail en groupe, des connaissances spécifiques aux disciplines et à la politique de sélection universitaire semblent intervenir dans le processus de légitimation des rapports sociaux dans les groupes au niveau des attributions. En tentant une articulation entre les concepts d?ancrage des représentations sociales, d?attribution et de socialisation, cette thèse permet ainsi de souligner la pertinence qu?il y a à insérer une problématique en termes de croyances idéologiques dans l?étude des groupes sociaux.<br/><br/>Heider?s approach of responsibility attributions almost exclusively emphasized on an individualistic point of view ; i.e. focusing at an intraindividual and interpersonnal level of analysis according to Doise?s distinction. The reflexions and empirical studies presented here firstly aim at broaden this perspective by taking socio-structural as well as societal levels of analysis into account. Secondly, it is to test this approach in the particular domain of organized groups. Manipulation of the structure of social relations in work groups on screenplays were undertaken (in a population of students from the Lausanne University). Hence, the main goal of these studies is to test the impact of the social ancoring of social representations in the responsibility processes in terms of legitimation or opposition to the group organization. All in all, the results show that social structures are powerfull predictors of the formation of social representations of a work situation and so forth of the attribution process. Nevertheless hegemonic ideological beliefs, such as Economical System Justification, do play a substantial moderating role in this process. It also proves to be evolving through time. The present findings show that a complexe process of socialization is occuring during the student?s university life. Indeed, the results let us believe that ideological beliefs may not interact anytime in the group?s perception and in the construction of the representation of the situation. In the same time, it seems that more discipline specific oriented knowledge and the impact of selection policy at the Lausanne University also predict the groupe legimation process and interfer with the ideological beliefs. Trying to articulate concepts of fields of research like social representations, attribution and socialization, the present thesis allows to underline the heuristic potential of reabilitating ideological beliefs at a dispositional level in the study of group process.