The adaptive function of melanin-based coloration in the tawny owl (Strix aluco) ; the proximate role of the melanocortin system

Colour polymorphism is common in wild population. One of the main questioning of evolutionary biologists is to understand how different colour variants could have evolved and be maintained in fluctuating environments, a selective process that forces individuals to constantly adapt their strategies in order to survive. This issue is particularly true for traits that are genetically inherited. Natural selection erodes genotypes with lowest fitness (less adapted), reducing in turn global genetic variation within population. In this context, the study of the evolution and maintenance of melanin- based coloration is relevant since inter-individual variation in the deposition of these pigments is common in animal and plant kingdoms and is under strong genetic control. In this thesis, I focus on the specific case of the tawny owl (Strix aluco), a species displaying continuous variation in reddish pheomelanin-based coloration. Interestingly, empirical studies highlighted covariations between melanin-based coloration and important behavioural, physiological and life history traits. Recently, a genetic model pointed out the melanocortin system and their pleiotropic effects as a potential regulator of these covariations. Accordingly, this PhD thesis further investigates colour-specific behavioural, physiological, or life history strategies, while examining the proximate mechanisms underlying these reaction norms. We found that differently coloured tawny owls differently resolve fundamental trade-off between offspring number and quality (Chapter 1), light melanic individuals producing many low- quality offspring and dark, melanic ones producing few high-quality offspring. These reproductive strategies are likely to induce alternative physiological constraints. Indeed, we demonstrated that light melanic individuals produced higher levels of reactive oxygen species (ROS, Chapter 2), but also expressed higher levels of antioxidant (GSH, Chapters 2 & 3). Interestingly, we showed that light melanic breeding females could modulate their POMC prohormone levels according to the environmental conditions, while dark reddish ones produced constant levels of this prohormone {Chapter 4). Finally, we highlighted colour-specific patterns of prohormone convertase 1 (PCI) gene expression (Chapter 5), an enzyme responsible for POMC prohormone processing to ACTH and a- MSH, for instance. Altogether, these results provide strong evidence of colour-specific strategies, light and melanic tawny owls better coping with stressful and relaxed environments, respectively. Variation in melanin-based coloration is likely to be maintained by the heterogeneity of our study area and strong environmental stochasticity within and between years, these process favouring differently coloured tawny owls at different periods of time. From a proximate point of view, this PhD thesis supports the hypothesis that covariations between phenotypic traits and melanin-based coloration stems from the melanocortin system, especially the fundamental role of POMC gene expression and its processing to melanocortin peptides. - Le polymorphisme de couleur est une variation phénotypique très fréquente dans la nature. En biologie évolutive, une des problématiques clés est donc de comprendre comment différent morphes de couleur peuvent être apparus et maintenus au cours du temps dans des environnements aussi variables que les nôtres, surtout que ces fluctuations forcent ces morphes à s'adapter constamment pour assurer leur survie. Cette thématique est particulièrement réelle lorsque les variations phénotypiques sont héréditaires et donc sous forte influence génétique. La sélection naturelle a en effet le pouvoir d'éroder rapidement la variation génétique en éliminant les génotypes mal adaptés. Dans ce sens, l'étude de l'évolution, et de la maintenance de la coloration mélanique est donc tout à fait pertinente car la variation de coloration entre individus est très répandue à travers les règnes animal et végétal et sous forte influence génétique. Dans cette thèse, je me suis concentré sur le cas spécifique de la chouette hulotte (Strix aluco), une espèce présentant une variation continue dans la déposition de pigments pheomélaniques roux. De précédentes études ont déjà montré que cette variation de coloration était associée avec des variations de traits comportementaux, physiologiques ou d'histoire de vie. Récemment, une étude a souligné l'importance du système des mélanocortines et de leurs effets pléiotropes dans la régulation de ces covariations. En conséquence, cette thèse de doctoral a pour but d'étudier un peu plus les stratégies comportementales, physiologiques ou d'histoire de vie spécifiques à chaque morphe de couleur, tout en examinant un peu plus les mécanismes proximaux potentiellement à la base de ces normes de réactions. Nous constatons tout d'abord que les morphes de couleurs étaient associés à différentes stratégies dans la résolution de compromis telle que la production de beaucoup de jeunes ou des jeunes de qualité (Chapitre 1). Les morphes gris (dit peu mélaniques) ont tendance à produire beaucoup de jeunes mains de moindre qualité, alors que les morphes roux (dit fortement mélaniques) produisent moins de jeunes mais de meilleure qualité. Ces stratégies sont susceptibles alors d'induire certaines contraintes physiologiques. Par exemple, nous montrons que les morphes gris produisent plus de dérivés réactifs de l'oxygène (ROS, Chapitre 2), mais aussi plus d'antioxydants (GSH, Chapitres 2 & 3). Nous montrons ensuite que les femelles grises ont une plus grande capacité à moduler leur niveau de POMC prohormone dans le sang en fonction des conditions environnementales, alors que les femelles rousses gardent un niveau constant (Chapitre 4). Finalement, nous démontrons que les patterns d'expression du gène codant pour la prohormone convertase 1 varient chez des jeunes issus de parents gris ou roux (Chapitre 5). Ceci est particulièrement intéressant car cette enzyme permet de scinder la POMC prohormone en plusieurs peptides importants tels que l'ACTH ou l'a-MSH. En conclusion, ces résultats démontrent qu'il y a bel et bien des stratégies évolutives différentes entre les morphes de couleurs, les chouettes hulottes grises et rousses étant respectivement plus adaptés à des environnements stressants ou favorables. L'hétérogénéité de notre zone d'étude et la stochasticité environnementale qui caractérise ses habitats pourraient donc agir comme une source de sélection temporelle, laquelle favoriserait les différents morphes de couleurs à diverses périodes. D'un point de vue plus proximale maintenant, cette thèse de doctorat soutient l'hypothèse que les covariations observées entre la coloration mélanique et des traits phénotypiques importants sont modulées par les effets pléiotropes du système des mélanocortines, et met en avant le rôle prépondérant que pourrait jouer l'expression du gène POMC et sa post traduction en mélanocortines.

Angiotensin II-mediated adaptive and maladaptive remodeling of cardiomyocyte excitation-contraction coupling.

Cardiac hypertrophy is associated with alterations in cardiomyocyte excitation-contraction coupling (ECC) and Ca(2+) handling. Chronic elevation of plasma angiotensin II (Ang II) is a major determinant in the pathogenesis of cardiac hypertrophy and congestive heart failure. However, the molecular mechanisms by which the direct actions of Ang II on cardiomyocytes contribute to ECC remodeling are not precisely known. This question was addressed using cardiac myocytes isolated from transgenic (TG1306/1R [TG]) mice exhibiting cardiac specific overexpression of angiotensinogen, which develop Ang II-mediated cardiac hypertrophy in the absence of hemodynamic overload. Electrophysiological techniques, photolysis of caged Ca(2+) and confocal Ca(2+) imaging were used to examine ECC remodeling at early ( approximately 20 weeks of age) and late ( approximately 60 weeks of age) time points during the development of cardiac dysfunction. In young TG mice, increased cardiac Ang II levels induced a hypertrophic response in cardiomyocyte, which was accompanied by an adaptive change of Ca(2+) signaling, specifically an upregulation of the Na(+)/Ca(2+) exchanger-mediated Ca(2+) transport. In contrast, maladaptation was evident in older TG mice, as suggested by reduced sarcoplasmic reticulum Ca(2+) content resulting from a shift in the ratio of plasmalemmal Ca(2+) removal and sarcoplasmic reticulum Ca(2+) uptake. This was associated with a conserved ECC gain, consistent with a state of hypersensitivity in Ca(2+)-induced Ca(2+) release. Together, our data suggest that chronic elevation of cardiac Ang II levels significantly alters cardiomyocyte ECC in the long term, and thereby contractility, independently of hemodynamic overload and arterial hypertension.

Mechanism of HFR1 function in adaptive growth responses in "Arabidopsis thaliana"

AbstractPlants are sessile organisms, which have evolved an astonishing ability to sense changes in their environment. Depending on the surrounding conditions, such as changes in light and temperature, plants modulate the activity of important transcriptional regulators. The shade avoidance syndrome (SAS) is one important mechanism for shade-intolerant plants to adapt their growth in high vegetative density. In shaded conditions plants sense a diminished red/far-red ratio via the phytochrome system and respond with morphological changes such as elongation growth of stems and petioles. The Phytochrome Interacting Factors 4 and 5 (PIF4 and PIF5) are positive regulators of the SAS and required for a full response (Lorrain et al, 2008). They regulate the SAS by inducing the expression of shade avoidance marker genes such as PIL1, ATHB2, XTR7 and HFR1 (Hornitschek et al, 2009; Lorrain et al, 2008).I investigated the molecular mechanism underlying the regulation of the SAS by HFR1 (long Hypocotyl in FR light). Although HFR1 is a PIF-related bHLH transcription factor, we discovered that HFR1 is a non-DNA binding protein. Moreover, we revealed that HFR1 inhibits an exaggerated SAS by forming non-DNA binding heterodimers with PIF4 and PIF5 (Hornitschek et al, 2009). This negative feedback loop is an important mechanism to limit elongation growth also in elevated temperatures. HFR1 accumulation and activity are highly temperature-dependent and the increased activity of HFR1 at warmer temperatures also provides an important restraint on PIF4-driven elongation growth (Foreman et al, 2011).Finally we performed a genome-wide analysis to determine how PIF4 and PIF5 regulate growth in response to shade. We identified potential PIF5- target genes, which represent many well-known shade-responsive genes. Our analysis of gene expression also revealed a role of PIF4 and PIF5 in simulated sun possibly via the regulation of auxin sensitivity.RésuméLes plantes sont des organismes sessiles ayant développé une capacité surprenante à détecter des changements dans leur environnement. En fonction des conditions extérieures, telles que les variations de lumière ou de température, elles adaptent l'activité d'importants régulateurs transcriptionnels. Le syndrome d'évitement de l'ombre (SAS), est un mécanisme important pour les plantes intolérantes à l'ombre leur permettant d'adapter leur croissance lorsqu'elles se développent dans des conditions de végétations très denses. Dans ces conditions, les plantes détectent une réduction de la quantité relative de lumière rouge par rapport à la lumière rouge-lointain (rapport R/FR). Ce changement, perçu via le système des phytochromes, induit des modifications morphologiques telle qu'une élongation des tiges et des pétioles. Les protéines PIF4 et PIF5 (Phytochrome Interacting Factors) sont des régulateurs positifs du SAS et sont nécessaires pour une réponse complète (Lorrain et al, 2008). Ces facteurs de transcription régulent le SAS en induisant l'expression de gènes marqueurs de cette réponse tels que PIL1, ATHB2, XTR7 et HFR1 (Hornitschek et al, 2009; Lorrain et al, 2008).J'ai étudié les mécanismes moléculaires sous-jacents à la régulation du SAS par HFR1 (long Hypocotyl in FR light). HFR1 est un facteur de transcription type bHLH de la famille des PIF, quoique nous ayons découvert que HFR1 est une protéine ne se liant pas à Γ ADN. Nous avons montré que HFR1 inhibe un SAS exagéré en formant des heterodimères avec PIF4 et PIF5 (Hornitschek et al, 2009). Nous avons également montré que cette boucle de régulation négative est également un mécanisme important pour limiter la croissance de l'élongation dans des conditions de fortes températures. De plus l'accumulation et l'activité de HFR1 augmentent avec la température ce qui permet d'inhiber plus fortement l'effet activateur de PIF4 sur la croissance.Enfin, nous avons effectué une analyse génomique à large échelle afin de déterminer comment PIF4 et PIF5 régulent la croissance en réponse à l'ombre. Nous avons identifié les gènes cibles potentiels de PIF5, correspondant en partie à des gènes connus dans la réponse de l'évitement de l'ombre. Notre analyse de l'expression des gènes a également révélé un rôle important de PIF4 et PIF5 dans des conditions de croissance en plein soleil, probablement via la régulation de la sensibilité à l'auxine.

Evolution of self-organized division of labor in a response threshold model.

Division of labor in social insects is determinant to their ecological success. Recent models emphasize that division of labor is an emergent property of the interactions among nestmates obeying to simple behavioral rules. However, the role of evolution in shaping these rules has been largely neglected. Here, we investigate a model that integrates the perspectives of self-organization and evolution. Our point of departure is the response threshold model, where we allow thresholds to evolve. We ask whether the thresholds will evolve to a state where division of labor emerges in a form that fits the needs of the colony. We find that division of labor can indeed evolve through the evolutionary branching of thresholds, leading to workers that differ in their tendency to take on a given task. However, the conditions under which division of labor evolves depend on the strength of selection on the two fitness components considered: amount of work performed and on worker distribution over tasks. When selection is strongest on the amount of work performed, division of labor evolves if switching tasks is costly. When selection is strongest on worker distribution, division of labor is less likely to evolve. Furthermore, we show that a biased distribution (like 3:1) of workers over tasks is not easily achievable by a threshold mechanism, even under strong selection. Contrary to expectation, multiple matings of colony foundresses impede the evolution of specialization. Overall, our model sheds light on the importance of considering the interaction between specific mechanisms and ecological requirements to better understand the evolutionary scenarios that lead to division of labor in complex systems. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00265-012-1343-2) contains supplementary material, which is available to authorized users.

Adaptive statistical iterative reconstruction reduces patient radiation dose in neuroradiology CT studies.

INTRODUCTION: Adaptive statistical iterative reconstruction (ASIR) can decrease image noise, thereby generating CT images of comparable diagnostic quality with less radiation. The purpose of this study is to quantify the effect of systematic use of ASIR versus filtered back projection (FBP) for neuroradiology CT protocols on patients' radiation dose and image quality. METHODS: We evaluated the effect of ASIR on six types of neuroradiologic CT studies: adult and pediatric unenhanced head CT, adult cervical spine CT, adult cervical and intracranial CT angiography, adult soft tissue neck CT with contrast, and adult lumbar spine CT. For each type of CT study, two groups of 100 consecutive studies were retrospectively reviewed: 100 studies performed with FBP and 100 studies performed with ASIR/FBP blending factor of 40 %/60 % with appropriate noise indices. The weighted volume CT dose index (CTDIvol), dose-length product (DLP) and noise were recorded. Each study was also reviewed for image quality by two reviewers. Continuous and categorical variables were compared by t test and free permutation test, respectively. RESULTS: For adult unenhanced brain CT, CT cervical myelography, cervical and intracranial CT angiography and lumbar spine CT both CTDIvol and DLP were lowered by up to 10.9 % (p < 0.001), 17.9 % (p = 0.005), 20.9 % (p < 0.001), and 21.7 % (p = 0.001), respectively, by using ASIR compared with FBP alone. Image quality and noise were similar for both FBP and ASIR. CONCLUSION: We recommend routine use of iterative reconstruction for neuroradiology CT examinations because this approach affords a significant dose reduction while preserving image quality.

Active Contour-Based Segmentation of Head and Neck with Adaptive Atlas Selection

This paper presents automated segmentation of structuresin the Head and Neck (H\&N) region, using an activecontour-based joint registration and segmentation model.A new atlas selection strategy is also used. Segmentationis performed based on the dense deformation fieldcomputed from the registration of selected structures inthe atlas image that have distinct boundaries, onto thepatient's image. This approach results in robustsegmentation of the structures of interest, even in thepresence of tumors, or anatomical differences between theatlas and the patient image. For each patient, an atlasimage is selected from the available atlas-database,based on the similarity metric value, computed afterperforming an affine registration between each image inthe atlas-database and the patient's image. Unlike manyof the previous approaches in the literature, thesimilarity metric is not computed over the entire imageregion; rather, it is computed only in the regions ofsoft tissue structures to be segmented. Qualitative andquantitative evaluation of the results is presented.

Insights from insects about adaptive social information use.

Copying others can greatly improve individual fitness and is fundamental for the organisation of societies. Yet in some situations it is better to ignore social information and either explore the world individually or use personal information obtained through prior experience. Insects provide excellent models to study the strategic use of social information, but insights from recent research have rarely been viewed in the light of social learning strategies. Here we discuss how insects tailor their reliance on social information to those circumstances for which it is most beneficial, and suggest that insects and vertebrates use similar information-use strategies. We highlight future research avenues, including the use of molecular tools to study the genetic and genomic basis of social information use.

Exploring the proposed DSM-5 diagnostic threshold and severity scale for the alcohol use disorder

Aims :¦Several studies have questioned the validity of separating the diagnosis of alcohol abuse from that of alcohol dependence, and the DSM-5 task force has proposed combining the criteria from these two diagnoses to assess a single category of alcohol use disorders (AUD). Furthermore, the DSM-5 task force has proposed including a new 2-symptom threshold and a severity scale based on symptom counts for the AUD diagnosis. The current study aimed to examine these modifications in a large population-based sample.¦Method :¦Data stemmed from an adult sample (N=2588 ; mean age 51.3 years (s.d.: 0.2), 44.9% female) of current and lifetime drinkers from the PsyCoLaus study, conducted in the Lausanne area in Switzerland. AUDs and validating variables were assessed using a semi-structured diagnostic interview for the assessment of alcohol¦and other major psychiatric disorders. First, the adequacy of the proposed 2- symptom threshold was tested by comparing threshold models at each possible cutoff and a linear model, in relation to different validating variables. The model with the smallest Akaike Criterion Information (AIC) value was established as the best¦model for each validating variable. Second, models with varying subsets of individual AUD symptoms were created to assess the associations between each symptom and the validating variables. The subset of symptoms with the smallest AIC value was established as the best subset for each validator.¦Results :¦1) For the majority of validating variables, the linear model was found to be the best fitting model. 2) Among the various subsets of symptoms, the symptoms most frequently associated with the validating variables were : a) drinking despite having knowledge of a physical or psychological problem, b) having had a persistent desire or unsuccessful efforts to cut down or control drinking and c) craving. The¦least frequent symptoms were : d) drinking in larger amounts or over a longer period than was intended, e) spending a great deal of time in obtaining, using or recovering from alcohol use and f) failing to fulfill major role obligations.¦Conclusions :¦The proposed DSM-5 2-symptom threshold did not receive support in our data. Instead, a linear AUD diagnosis was supported with individuals receiving an increasingly severe AUD diagnosis. Moreover, certain symptoms were more frequently associated with the validating variables, which suggests that these¦symptoms should be considered as more severe.

An Adaptive Field Detection Method For Bridge Scour Monitoring Using Motion-Sensing Radio Transponders (RFIDs), TR-617, 2014

A comprehensive field detection method is proposed that is aimed at developing advanced capability for reliable monitoring, inspection and life estimation of bridge infrastructure. The goal is to utilize Motion-Sensing Radio Transponders (RFIDS) on fully adaptive bridge monitoring to minimize the problems inherent in human inspections of bridges. We developed a novel integrated condition-based maintenance (CBM) framework integrating transformative research in RFID sensors and sensing architecture, for in-situ scour monitoring, state-of-the-art computationally efficient multiscale modeling for scour assessment.

The evolution, maintenance and adaptive function of genetic colour polymorphism in birds.

The hypothesis that ornaments can honestly signal quality only if their expression is condition-dependent has dominated the study of the evolution and function of colour traits. Much less interest has been devoted to the adaptive function of colour traits for which the expression is not, or is to a low extent, sensitive to body condition and the environment in which individuals live. The aim of the present paper is to review the current theoretical and empirical knowledge of the evolution, maintenance and adaptive function of colour plumage traits for which the expression is mainly under genetic control. The finding that in many bird species the inheritance of colour morphs follows the laws of Mendel indicates that genetic colour polymorphism is frequent. Polymorphism may have evolved or be maintained because each colour morph facilitates the exploitation of alternative ecological niches as suggested by the observation that individuals are not randomly distributed among habitats with respect to coloration. Consistent with the hypothesis that different colour morphs are linked to alternative strategies is the finding that in a majority of species polymorphism is associated with reproductive parameters, and behavioural, life-history and physiological traits. Experimental studies showed that such covariations can have a genetic basis. These observations suggest that colour polymorphism has an adaptive function. Aviary and field experiments demonstrated that colour polymorphism is used as a criterion in mate-choice decisions and dominance interactions confirming the claim that conspecifics assess each other's colour morphs. The factors favouring the evolution and maintenance of genetic variation in coloration are reviewed, but empirical data are virtually lacking to assess their importance. Although current theory predicts that only condition-dependent traits can signal quality, the present review shows that genetically inherited morphs can reveal the same qualities. The study of genetic colour polymorphism will provide important and original insights on the adaptive function of conspicuous traits.

Genital Chlamydia trachomatis: understanding the roles of innate and adaptive immunity in vaccine research.

Chlamydia trachomatis is the leading cause of bacterial sexually transmitted disease worldwide, and despite significant advances in chlamydial research, a prophylactic vaccine has yet to be developed. This Gram-negative obligate intracellular bacterium, which often causes asymptomatic infection, may cause pelvic inflammatory disease (PID), ectopic pregnancies, scarring of the fallopian tubes, miscarriage, and infertility when left untreated. In the genital tract, Chlamydia trachomatis infects primarily epithelial cells and requires Th1 immunity for optimal clearance. This review first focuses on the immune cells important in a chlamydial infection. Second, we summarize the research and challenges associated with developing a chlamydial vaccine that elicits a protective Th1-mediated immune response without inducing adverse immunopathologies.

Activation of the NLRP3 inflammasome in dendritic cells induces IL-1beta-dependent adaptive immunity against tumors.

The therapeutic efficacy of anticancer chemotherapies may depend on dendritic cells (DCs), which present antigens from dying cancer cells to prime tumor-specific interferon-gamma (IFN-gamma)-producing T lymphocytes. Here we show that dying tumor cells release ATP, which then acts on P2X(7) purinergic receptors from DCs and triggers the NOD-like receptor family, pyrin domain containing-3 protein (NLRP3)-dependent caspase-1 activation complex ('inflammasome'), allowing for the secretion of interleukin-1beta (IL-1beta). The priming of IFN-gamma-producing CD8+ T cells by dying tumor cells fails in the absence of a functional IL-1 receptor 1 and in Nlpr3-deficient (Nlrp3(-/-)) or caspase-1-deficient (Casp-1(-/-)) mice unless exogenous IL-1beta is provided. Accordingly, anticancer chemotherapy turned out to be inefficient against tumors established in purinergic receptor P2rx7(-/-) or Nlrp3(-/-) or Casp1(-/-) hosts. Anthracycline-treated individuals with breast cancer carrying a loss-of-function allele of P2RX7 developed metastatic disease more rapidly than individuals bearing the normal allele. These results indicate that the NLRP3 inflammasome links the innate and adaptive immune responses against dying tumor cells.

THE USEFUL SIDE OF AMBIVALENCE: Ambivalent attitudes can be adaptive and socially valued

En s'inspirant de la littérature récente qui a dépeint l'ambivalence comme étant adaptative et en lien avec des comportements stratégiques, cette thèse examine le versant utile des attitudes ambivalentes. Elle met tout d'abord en évidence que son expression peut-être sciemment contrôlée et mise en avant pour des raisons d'auto-présentation. De plus, elle démontre que les individus peuvent présenter une attitude ambivalente afin de gagner l'approbation sociale sur un objet d'attitude controversé alors que l'inverse a été observé sur des objets consensuels (Première ligne de recherche). Cette thèse a également révélé que l'expression d'attitudes ambivalentes pouvait amener à être valorisé socialement. En effet, contrairement à des attitudes plus tranchées (pro-normatives ou contre-normatives), les attitudes ambivalentes ont été évaluées de façon plus importante sur la dimension de l'utilité sociale (une dimension qui indique la compétence d'autrui ou encore la propension à évoluer dans la hiérarchie sociale). La valorisation de l'ambivalence n'est apparue que sur la dimension de l'utilité sociale et non sur la dimension de la désirabilité sociale (une dimension qui indique la sympathie d'autrui ainsi que la propension à être apprécié socialement). De plus, ce résultat a été observé sur des thèmes controversés et non sur des thèmes consensuels (Seconde ligne de recherche). Dans l'ensemble cette thèse soutient une approche de l'ambivalence comme donnant lieu à des bénéfices. Elle peut également ouvrir la voie à l'étude de l'ambivalence en lien avec la pensée critique. - Drawing on the recent literature that portrayed ambivalence as being adaptive and linked with strategic behaviors, this thesis examines the useful side of ambivalent attitudes. It first revealed that the expression of ambivalent attitudes could be controlled and purposely displayed for self-presentational concerns. Furthermore, it demonstrated that people could put ambivalence forward to gain social approval when expressing it on controversial social issues, whereas the opposite was true on consensual social issues (First line of research). The thesis also revealed that the expression of ambivalent attitudes could lead to be socially valued. Indeed, contrary to clear-cut attitudes (either pro-normative or counter-normative attitudes), ambivalent attitudes have been evaluated the highest on the social utility dimension (a dimension indicating people's competence as well as the extent to which they are likely to climb in social hierarchy). The valorization of ambivalent attitudes only appeared on social utility and not on social desirability (a dimension indicating people's niceness as well as the extent to which they are likely to be socially appreciated). This effect was true on controversial social issues but not on consensual ones (Second line of research). Overall, this thesis provides support for an approach that conceives attitudinal ambivalence as leading to benefits. It also may open avenues for the study of ambivalence in relation with critical thinking.

Cardiac raptor deletion impairs adaptive hypertrophy, alters metabolic gene expression and causes heart failure in mice

Background: Mammalian target of rapamycin (mTOR), a central regulator of cell growth, is found in two structurally and functionally distinct multiprotein complexes called mTOR complex (mTORC)1 and mTORC2. The specific roles of each of these branches of mTOR signaling have not been dissected in the adult heart. In the present study, we aimed to bring new insights into the function of cardiac mTORC1-mediated signaling in physiological as well as pathological situations.Methods: We generated mice homozygous for loxP-flanked raptor and positive for the tamoxifen-inducible Cre recombinase (MerCreMer) under control of the α- myosin heavy chain promoter. The raptor gene encodes an essential component of mTORC1. Gene ablation was induced at the age of 10-12 weeks, and two weeks later the raptor cardiac-knockout (raptor-cKO) mice started voluntary cagewheel exercise or were subjected to transverse aortic constriction (TAC) to induce pressure overload.Results: In sedentary raptor-cKO mice, ejection fractions gradually decreased, resulting in significantly reduced values at 38 days (P < 0.001). Raptor-cKO mice started to die during the fifth week after the last tamoxifen injection. At that time, the mortality rate was 36% in sedentary (n = 11) and 64% in exercising (n = 14) mice. TAC-induced pressure overload resulted in severe cardiac dysfunction already at earlier timepoints. Thus, at 7-9 days after surgery, ejection fraction and fractional shortening values were 22.3% vs 43.5% and 10.2% vs 21.5% in raptor-cKO vs wild-type mice, respectively. This was accompanied by significant reductions of ventricular wall and septal thickness as well as an increase in left ventricular internal diameter. Moreover, ventricular weight to tibial length ratios were increased in wild-type, but not in the raptor-cKO TAC mice. Together, this shows that raptor-cKO mice rapidly developed dilated cardiomyopathy without going through a phase of adaptive hypertrophy. Expression of ANP and β-MHC was induced in all raptor-cKO mice irrespective of the cardiac load conditions. Consistent with reduced mTORC1 activity, phosphorylation of ribosomal S6 kinase and 4E-BP1 was blunted, indicating reduced protein synthesis. Moreover, expression of multiple genes involved in the regulation of energy metabolism was altered, and followed by a shift from fatty acid to glucose oxidation.Conclusion: Our study suggests that mTORC1 coordinates protein and energy metabolic pathways in the heart. Moreover, we demonstrate that raptor is essential for the cardiac adaptation to increased workload and importantly, also for normal physiological cardiac function.