Frames and games

Decision-makers are sometimes influenced by the way in which choice situations are presented to them or "framed" This can be seen as an important challenge to the social sciences, since strong and pervasive framing effects would make it difficult to study human behavior in a synthetic or theoretic manner. We present results from experiments with dilemma games designed to shed light on the effects of several frame variations. We study, among others, the particular public bad frame used by Andreoni (1995) and two more naturalistic frames involving stories. Our results show that none of the frame manipulations have a significant effect on average behavior, but we do find some effects on extreme behavior. We also find that incentives do matter where frames do not matter.

Memòria justificativa de l'estada de recerca

Estudi elaborat a partir d’una estada a l’Associação para o Desenvolvimento da Aerodinânica Industrial (ADAI) de la Universitat de Coimbra, Portugal, entre març i juliol de 2006. Aquesta disposa d'un laboratori d'assaigs i té medis suficients per a cremar de manera controlada parcel•les prèviament delimitades en terreny forestal. Això permet observar el fenomen dels incendis forestals a dues escales de treball diferents. L’objectiu ha estat l’obtenció de dades experimentals sobre la propagació de fronts de flames que avancen sobre combustible tractat amb retardants sota l’efecte del pendent o el vent. S’ha participat en proves experimentals de camp i se n’han realitzat dues en instal•lacions de laboratori en què l’efecte del pendent o de la velocitat del vent podia ser variat. Degut a l’elevat nombre de variables que entren en joc l’anàlisi acurada de les dades encara està en procés.

Influence of experimental illumination and seasonal variation on crossbreending mating in the snail Biomphalaria Glabrata

The crossbreeding activities of the Schistosoma mansoni vector snail Biomphalaria glabrata were counted in a laboratory aquarium throughout the year under two regimes of 12h light: 12h dark from 7 A., M. to 10 P. M. Mating increased significantly in Authmn and Winter and just missed a significant inverse correlation with temperature and a direct one with locomotion. Other similar experiments were carried out to compare mating under various ilumination conditions in complete daily cycle measurements. Mating counts decreased under the regimes which submited snail to a total exposure of 12h light and 12 dark during a daily cycle in the following sequence: 12h light: 12h dark alternating hourly with light gradient, 12h light: 12h dark, 1h light: 1h dark and 12h dark: 12h light. Under two constant illuminations, the mating scored less than under the previous conditions, except under 12h light. Under darkeness the mating count was lower than light conditions. There was no way to differentiate the night and day rhythms of mating on different days in each regime, except for mating under 12h light: 12 dark alternating with light gradient, constant dark and 12h dark: 12h light conditions. Mating increased in certain light and temperature conditions, in wich the intensities, should have an optimum value.

Partner Selection into Policy Relevant Field Experiments

This study investigates the issue of self-selection of stakeholders into participation and collaboration in policy-relevant experiments. We document and test the implications of self-selection in the context of randomised policy experiment we conducted in primary schools in the UK. The main questions we ask are (1) is there evidence of selection on key observable characteristics likely to matter for the outcome of interest and (2) does selection matter for the estimates of treatment eff ects. The experimental work consists in testing the e ffects of an intervention aimed at encouraging children to make more healthy choices at lunch. We recruited schools through local authorities and randomised schools across two incentive treatments and a control group. We document the selection taking place both at the level of local authorities and at the school level. Overall we nd mild evidence of selection on key observables such as obesity levels and socio-economic characteristics. We find evidence of selection along indicators of involvement in healthy lifestyle programmes at the school level, but the magnitude is small. Moreover, We do not find signifi cant di erences in the treatment e ffects of the experiment between variables which, albeit to a mild degree, are correlated with selection into the experiment. To our knowledge, this is the rst study providing direct evidence on the magnitude of self-selection in fi eld experiments.

Effects of stress on economic decision-making: Evidence from laboratory experiments

The ways in which preferences respond to the varying stress of economic environments is a key question for behavioral economics and public policy. We conducted a laboratory experiment to investigate the effects of stress on financial decision making among individuals aged 50 and older. Using the cold pressor task as a physiological stressor, and a series of intelligence tests as cognitive stressors, we find that stress increases subjective discounting rates, has no effect on the degree of risk-aversion, and substantially lowers the effort individuals make to learn about financial decisions.

Caracterització de la població de mosquit tigre asiàtic (Aedes albopictus) al municipi de Rubí i anàlisi de l'impacte ambiental associat en el medi socioeconòmic

Aedes albopictus (Skuse,1894) va ser detectada a Catalunya l’any 2004 a Sant Cugat del Vallés. El mosquit tigre asiàtic és espècie invasora que causa impactes negatius a nivell econòmic, sociosanitàri i mediambiental, principalment per les seves molestes picades però també pel potencial risc que té com a vector transmissor de diverses malalties com la febre groga i el dengue. En aquest treball és vol avaluar i estudiar la situació actual de l’espècie al municipi de Rubí (Vallés Occidental) a través de l’estudi per paranys d’oviposició. També és vol avaluar l’impacte que el mosquit tigre asiàtic té en el medi socioeconòmic a través de la metodologia de experiments d’elecció.

Quelle assistance psychologique pour les couples requérant une aide médicale à la procréation [Which psychological support for couples seeking medical assistance for procreation?]

OBJECTIVES: The objective of our qualitative study was to define modalities of psychological support to be offered to couples seeking medically assisted procreation. MATERIAL AND METHODS: Forty couples participated in a semi-structured videotaped interview, which touched on themes such as personal and family histories, the couple's relationship, etc. We focused on the "narrative mobility", that is the way in which the couples transmit their personal and family history during the interview and the interviewer's impression that he may or may not share this with the couples. RESULTS: Observed differences in narrative mobility led us to distinguish three groups of couples and to propose various types of psychological support. DISCUSSION AND CONCLUSION: This exploratory study, with its interest for the narrative mobility, concerns the couples' capacity to stand back from their own story as responsible interlocutors. We made the hypothesis that this capacity is linked to their capacity to handle their emotional stress, to act as partners to the medical team and to prepare themselves for their future parenthood.

Design and analysis of ChIP-Seq experiments for nuclear factor I DNA-binding proteins

SUMMARY : Eukaryotic DNA interacts with the nuclear proteins using non-covalent ionic interactions. Proteins can recognize specific nucleotide sequences based on the sterical interactions with the DNA and these specific protein-DNA interactions are the basis for many nuclear processes, e.g. gene transcription, chromosomal replication, and recombination. New technology termed ChIP-Seq has been recently developed for the analysis of protein-DNA interactions on a whole genome scale and it is based on immunoprecipitation of chromatin and high-throughput DNA sequencing procedure. ChIP-Seq is a novel technique with a great potential to replace older techniques for mapping of protein-DNA interactions. In this thesis, we bring some new insights into the ChIP-Seq data analysis. First, we point out to some common and so far unknown artifacts of the method. Sequence tag distribution in the genome does not follow uniform distribution and we have found extreme hot-spots of tag accumulation over specific loci in the human and mouse genomes. These artifactual sequence tags accumulations will create false peaks in every ChIP-Seq dataset and we propose different filtering methods to reduce the number of false positives. Next, we propose random sampling as a powerful analytical tool in the ChIP-Seq data analysis that could be used to infer biological knowledge from the massive ChIP-Seq datasets. We created unbiased random sampling algorithm and we used this methodology to reveal some of the important biological properties of Nuclear Factor I DNA binding proteins. Finally, by analyzing the ChIP-Seq data in detail, we revealed that Nuclear Factor I transcription factors mainly act as activators of transcription, and that they are associated with specific chromatin modifications that are markers of open chromatin. We speculate that NFI factors only interact with the DNA wrapped around the nucleosome. We also found multiple loci that indicate possible chromatin barrier activity of NFI proteins, which could suggest the use of NFI binding sequences as chromatin insulators in biotechnology applications. RESUME : L'ADN des eucaryotes interagit avec les protéines nucléaires par des interactions noncovalentes ioniques. Les protéines peuvent reconnaître les séquences nucléotidiques spécifiques basées sur l'interaction stérique avec l'ADN, et des interactions spécifiques contrôlent de nombreux processus nucléaire, p.ex. transcription du gène, la réplication chromosomique, et la recombinaison. Une nouvelle technologie appelée ChIP-Seq a été récemment développée pour l'analyse des interactions protéine-ADN à l'échelle du génome entier et cette approche est basée sur l'immuno-précipitation de la chromatine et sur la procédure de séquençage de l'ADN à haut débit. La nouvelle approche ChIP-Seq a donc un fort potentiel pour remplacer les anciennes techniques de cartographie des interactions protéine-ADN. Dans cette thèse, nous apportons de nouvelles perspectives dans l'analyse des données ChIP-Seq. Tout d'abord, nous avons identifié des artefacts très communs associés à cette méthode qui étaient jusqu'à présent insoupçonnés. La distribution des séquences dans le génome ne suit pas une distribution uniforme et nous avons constaté des positions extrêmes d'accumulation de séquence à des régions spécifiques, des génomes humains et de la souris. Ces accumulations des séquences artéfactuelles créera de faux pics dans toutes les données ChIP-Seq, et nous proposons différentes méthodes de filtrage pour réduire le nombre de faux positifs. Ensuite, nous proposons un nouvel échantillonnage aléatoire comme un outil puissant d'analyse des données ChIP-Seq, ce qui pourraient augmenter l'acquisition de connaissances biologiques à partir des données ChIP-Seq. Nous avons créé un algorithme d'échantillonnage aléatoire et nous avons utilisé cette méthode pour révéler certaines des propriétés biologiques importantes de protéines liant à l'ADN nommés Facteur Nucléaire I (NFI). Enfin, en analysant en détail les données de ChIP-Seq pour la famille de facteurs de transcription nommés Facteur Nucléaire I, nous avons révélé que ces protéines agissent principalement comme des activateurs de transcription, et qu'elles sont associées à des modifications de la chromatine spécifiques qui sont des marqueurs de la chromatine ouverte. Nous pensons que lés facteurs NFI interagir uniquement avec l'ADN enroulé autour du nucléosome. Nous avons également constaté plusieurs régions génomiques qui indiquent une éventuelle activité de barrière chromatinienne des protéines NFI, ce qui pourrait suggérer l'utilisation de séquences de liaison NFI comme séquences isolatrices dans des applications de la biotechnologie.

A drug administration decision support system

Drug delivery is one of the most common clinical routines in hospitals, and is critical to patients' health and recovery. It includes a decision making process in which a medical doctor decides the amount (dose) and frequency (dose interval) on the basis of a set of available patients' feature data and the doctor's clinical experience (a priori adaptation). This process can be computerized in order to make the prescription procedure in a fast, objective, inexpensive, non-invasive and accurate way. This paper proposes a Drug Administration Decision Support System (DADSS) to help clinicians/patients with the initial dose computing. The system is based on a Support Vector Machine (SVM) algorithm for estimation of the potential drug concentration in the blood of a patient, from which a best combination of dose and dose interval is selected at the level of a DSS. The addition of the RANdom SAmple Consensus (RANSAC) technique enhances the prediction accuracy by selecting inliers for SVM modeling. Experiments are performed for the drug imatinib case study which shows more than 40% improvement in the prediction accuracy compared with previous works. An important extension to the patient features' data is also proposed in this paper.

Three essays on leadership

ABSTRACT Samuel Bendahan, John Antonakis, Christian Zehnder, and François Pralong The relationship between power and immoral decisions has been discussed extensively by scientists and philosophers alike. Although the exercise of power is ubiquitous in social hierarchies, direct evidence on the impact of power on decision making is scarce. We use laboratory experiments to study whether more power leads to corruption. We manipulate power in the context of leader decision-making authority involving monetary stakes. Prior to the experiment, we also gathered extensive data on psychological and endocrinological individual differences. We find that an increase of power caused leaders to be more likely to engage in destructive, selfish behaviour, although the same subjects did not behave in this manner before their level of power was increased. We also show how individual differences affect the initial level of destructive behaviour and the corruption process. WHAT'S RIGHT FOR THE LEFT MAY NOT BE RIGHT FOR THE RIGHT: VALUE CONGRUENCE AND CHARISMA IN POLITICAL LEADERSHIP Samuel Bendahan ABSTRACT Value congruence between leaders and followers is important not only for follower commitment but also as part of the attributions followers make of leaders. I theorized that transformational leadership, which often is referred to as being value driven and having strong moral foundations, has differential effects depending on the values of the follower and whether these values are congruent with what the leader espouses. I designed an experiment to analyze how the political values of followers and leaders can influence followers' attributions regarding leaders. Within the context of political leadership, I found that transformational leaders were seen as more prototypical. Value congruence predicted prototypicality, which was strongly related to follower intentions to vote for the leader. Furthermore, followers with left-wing political values were more influenced by prototypical leaders than were followers with right-wing political values, presumably because of moral overtones of both left-wing ideology and transformational leadership. JUDGING LEADERSHIP POTENTIAL IN AN INTERVIEW: MODERATING EFFECT OF INTERVIEWER INTELLIGENCE ON INTERVIEWER COGNITIVE BUSYNESS, CANDIDATE PERFORMANCE-CUES EFFECTS, AND CANDIDATE ETHNICITY Samuel Bendahan, Philippe Jacquart, and John Antonakis ABSTRACT A large body of literature suggests that interviewers do not accurately rate candidates when using unstructured interviews and evaluation procedures that affect pre-interview expectations; however, the process by which these biases are produced is not well understood. We theorized several reasons for the sub-par performance of the unstructured interview. These factors, which we manipulated in the context of a videotaped interview of a candidate applying for a leadership position, include evaluator cognitive load, pre-interview performance cues regarding the candidate, and the ethnicity of the candidate. We also controlled for the intelligence of the evaluator. We found a significant four-way interaction between the manipulated factors and evaluators' cognitive abilities. The effects of the manipulated factors were all significantly less for evaluators who were high on general intelligence.

Characterization of the effects of IL-17F on CHO cell line generation

CHO is the most commonly used mammalian host for the generation of cell lines allowing for the production of high quality therapeutic proteins. The generation of such cell lines is a lengthy and resource-intensive process requiring extensive screening in order to isolate candidates with optimal characteristics, such as growth, stability and productivity. For this reason, the biotechnology industry invests much effort in attempts to optimize CHO expression systems in order to streamline and shorten the cell line selection process. Based on preliminary observations of a facilitated selection of CHO-GS cell lines expressing members of the IL-17 cytokine family, this study investigates the use of IL-17F as a novel enhancing factor for CHO cell line generation. Using two different CHO expression systems (exploiting GS and DHFR-based selection), we demonstrated that IL-17F expression caused a significant increase in the occurrence of colonies during the selection process. All colonies selected produced substantial amounts of IL-17F, suggesting that benefits were conferred, during selection, to those cells expressing the cytokine. Furthermore, transgene expression levels were significantly increased when the selection pressure was raised to a level that would not normally be permissive for colony selection (i.e. 100 |o.M MSX for the CHO-GS expression system or 1000 nM MTX for the CHO-DHFR system). Finally, IL-17F expression was also found to enhance the rate of appearance of clones during single cell subcloning in the absence of selection pressure. Overall, these benefits have the potential to allow a substantial reduction in the length of cell line generation while significantly increasing cell line productivity. Nevertheless, we found that the high IL-17F expression levels required to convey enhancing effects was a limitation when attempting to co-express IL-17F and a recombinant soluble protein of therapeutic interest from independent CMV promoters within the same expression vector. In order to understand and overcome this limitation, studies were designed to characterize the IL-17F enhancing effect at the molecular and cellular level. Regular supplementation of recombinant biologically-active IL-17F into the culture medium during cell line selection was not able to reproduce the enhancing effects of endogenous IL-17F expression. In addition, increased IL-17F expression correlated with increased CHO-GS selection transgene expression at the single cell level. This data suggested a possible effect of IL-17F on viral promoter activity or transgene mRNA stability. It also provided direct evidence that the cells expressing the highest amounts of IL-17F obtained the most benefit. Overall data obtained from these study implied that IL-17F may act through an intracellular mechanism, possibly exerted during secretion. We therefore initiated experiments designed to determine the specific compartment(s) within which IL-17F triggers its effect. This work has identified IL-17F as a potentially powerful tool to optimize the CHO cell line generation process. The characterization of this enhancing effect at the molecular level has given us several insights into overcoming the current limitations, thus paving the way for the development of a viable technology that can be exploited within the biotechnology industry. - La CHO est la cellule hôte de mammifere la plus couramment utilisée dans la création de lignée cellulaire produisant des protéines thérapeutiques de haute qualité. La génération de ces lignées cellulaires est un processus long et exigeant l'utilisation de techniques de sélection robustes afin d'isoler des candidats possédants les caractéristiques optimales de croissance, de productivité et de stabilité d'expression. Les industries biopharmaceutiques ont investi beaucoup d'efforts afin d'optimiser les systèmes d'expression CHO dans le but raccourcir la longueur du procédé de sélection de lignées cellulaires et aussi d'en augmenter l'efficacité. A partir d'observations préliminaires obtenues lors de la génération de lignées cellulaires CHO- GS exprimant une cytokine appartenant à la famille des IL-17, nous avons réalisé une étude portant sur l'utilisation de l'IL-17F humaine (IL-17F) comme nouveau facteur d'optimisation pour la génération de lignées cellulaires CHO. Nous avons démontré, en utilisant les deux systèmes de sélection et d'expression CHO couramment utilisés (le premier exploitant la GS et l'autre basée sur la DHFR), que l'expression de l'IL-17F permet une augmentation significative de la fréquence d'apparition de colonies durant le processus de sélection de lignées cellulaires. Les différentes colonies sélectionnées expriment des quantités substantielles d'IL-17F, suggérant un effet bénéfique lors de la sélection qui serait exclusivement conféré aux cellules exprimant la cytokine. En outre, le niveau d'expression du transgene se trouve significativement augmenté lorsque la pression de sélection est portée à un niveau habituellement trop élevé pour permettre la sélection de colonies (soit 100 |JM MSX pour le système d'expression CHO-GS ou 1000 nM MTX pour le système CHO- DHFR). Enfin, l'expression d'IL-17F permet également d'améliorer la vitesse d'apparition de clones pendant une étape de sous-clonage en l'absence de pression de sélection. L'ensemble de ces effets bénéfiques permettent une réduction substantielle de la durée de génération de lignées cellulaires tout en augmentant considérablement la productivité des lignées obtenues. Néanmoins, nous avons constaté que la nécessité d'exprimer des niveaux élevés d'IL-17F afin obtenir l'ensemble de ses effets bénéfiques devient une contrainte lors de l'utilisation d'un vecteur d'expression composé de deux promoteurs CMV indépendants pour la co-expression de la cytokine et d'une protéine soluble présentant un intérêt thérapeutique. Afin de mieux comprendre et de surmonter cette limitation, plusieurs études ont été effectuées dans le but de mieux caractériser l'effet de IL-17F au niveau subcellulaire. L'apport régulier en IL-17F recombinante et biologiquement active dans le milieu de culture lors de la sélection de lignées cellulaires ne permet pas de reproduire les effets bénéfiques observés par l'expression endogène d'IL-17F. En outre, nous avons constaté que, lors de l'utilisation du système CHO- GS, l'augmentation d'expression de 1TL-17F est corrélée à un accroissement de l'expression du marqueur de sélection au niveau cellulaire. Ces résultats suggèrent un possible effet d'IL- 17F sur l'activité des promoteurs viraux et ainsi fournissent une preuve directe que les cellules exprimant de haut niveau d'IL-17F sont celles qui en profitent le plus. L'ensemble de ces observations mettrait en avant que l'effet d'IL-17F se ferait selon un mécanisme intracellulaire. Nous avons donc étudié le(s) compartiment(s) spécifique(s) dans lequel IL-17F pourrait exercer son effet. Ce travail a permis de définir IL-17F comme un puissant outil pour l'optimisation des procédés de génération de lignées cellulaires CHO. La caractérisation de cette amélioration de l'effet au niveau moléculaire nous a donné plusieurs indications sur la manière de dépasser les limitations actuelles, ouvrant ainsi la voie au développement d'une technologie viable qui peut être exploitée pars l'industrie biotechnologique.

A way to play bankruptcy problems.

The commitment among agents has always been a difficult task, especially when they have to decide how to distribute the available amount of a scarce resource among all. On the one hand, there are a multiplicity of possible ways for assigning the available amount; and, on the other hand, each agent is going to propose that distribution which provides her the highest possible award. In this paper, with the purpose of making this agreement easier, firstly we use two different sets of basic properties, called Commonly Accepted Equity Principles, to delimit what agents can propose as reasonable allocations. Secondly, we extend the results obtained by Chun (1989) and Herrero (2003), obtaining new characterizations of old and well known bankruptcy rules. Finally, using the fact that bankruptcy problems can be analyzed from awards and losses, we define a mechanism which provides a new justification of the convex combinations of bankruptcy rules. Keywords: Bankruptcy problems, Unanimous Concessions procedure, Diminishing Claims mechanism, Piniles’ rule, Constrained Egalitarian rule. JEL classification: C71, D63, D71.

Modelos de viento aplicados a la mejora en la predicción de incendios forestales

La predicción de incendios forestales es uno de los grandes retos de la comunidad científica debido al impacto medioambiental, humano y económico que tienen en la sociedad. El comportamiento de este fenómeno es difícil de modelar debido a la gran cantidad de variables que intervienen y la dificultad que implica su correcta medición. Los simuladores de fuego son herramientas muy útiles pero, actualmente, los resultados que obtenemos tienen un alto grado de imprecisión. Desde nuestro grupo se ha trabajado en la predicción en dos etapas, donde antes de realizar cualquier predicción, se incorpora una etapa de ajuste de los parámetros de entrada para obtener mejores predicciones. Pese a la mejora que supone este nuevo paradigma de predicción, las simulaciones sobre incendios reales tienen un alto grado de error por el efecto de las condiciones meteorológicas que, usualmente, varían de manera notable durante el transcurso de la simulación. Uno de los factores más determinantes en el comportamiento de un incendio, junto con las características del terreno, es el viento. Los modelos de predicción son extremadamente sensibles al cambio en los componentes de dirección y velocidad del viento por lo que cualquier mejora que podamos introducir para mejorar la calidad de estas componentes influye directamente en la calidad de la predicción. Nuestro sistema de predicción utiliza la dirección y velocidad del viento de forma global en todo el terreno, y lo que proponemos con este trabajo es introducir un modelo de vientos que nos permita generar vientos locales en todas las celdas en las que se divide el terreno. Este viento local dependerá del viento general y de las características del terreno de dichas celdas. Consideramos que la utilización de un viento general no es suficiente para realizar una buena predicción del comportamiento de un incendio y hemos comprobado que la inclusión de un simulador de campo de vientos en nuestro sistema puede llegar a mejorar nuestras predicciones considerablemente. Los resultados obtenidos en los experimentos sintéticos que hemos realizado nos hacen ser optimistas, puesto que consideramos que la inclusión de componentes de viento locales permitirá mejorar nuestras predicciones en incendios reales.

Active Learning of Very-High Resolution Optical Imagery with SVM: Entropy vs Margin Sampling

An active learning method is proposed for the semi-automatic selection of training sets in remote sensing image classification. The method adds iteratively to the current training set the unlabeled pixels for which the prediction of an ensemble of classifiers based on bagged training sets show maximum entropy. This way, the algorithm selects the pixels that are the most uncertain and that will improve the model if added in the training set. The user is asked to label such pixels at each iteration. Experiments using support vector machines (SVM) on an 8 classes QuickBird image show the excellent performances of the methods, that equals accuracies of both a model trained with ten times more pixels and a model whose training set has been built using a state-of-the-art SVM specific active learning method

Molecular mechanisms for the transcriptional regulation of the Connexin36 gene expression in insulin-secreting cells

Résumé Régulation de l'expression de la Connexin36 dans les cellules sécrétrices d'insuline La communication intercellulaire est en partie assurée via des jonctions communicantes de type "gap". Dans la cellule ß pancréatique, plusieurs observations indiquent que le couplage assuré par des jonctions gap formées parla Connexine36 (Cx36) est impliqué dans le contrôle de la sécrétion de l'insuline. De plus, nous avons récemment démontré qu'un niveau précis d'expression de la Cx36 est nécessaire pour maintenir une bonne coordination de l'ensemble des cellules ß, et permettre ainsi une sécrétion synchrone et contrôlée d'insuline. Le développement du diabète et du syndrome métabolique est partiellement dû à une altération de la capacité des cellules ß à sécréter de l'insuline en réponse à une augmentation de la glycémie. Cette altération est en partie causée par l'augmentation prolongée des taux circulant de glucose, mais aussi de lipides, sous la forme d'acides gras libres, et de LDL (Low Density Lipoproteins), particules assurant le transport des acides gras et du cholestérol dans le sang. Nous avons étudié la régulation de l'expression de la Cx36 dans différentes conditions reflétant la physiopathologie du diabète de type 2 et du syndrome métabolique et démontré qu'une exposition prolongée à des concentrations élevées de glucose, de LDL, ainsi que de palmitate (acide gras saturé le plus abondant dans l'organisme), inhibent l'expression de la Cx36 dans les cellules ß. Cette inhibition implique l'activation de la PKA (Proteine Kinase A), qui stimule à son tour l'expression du facteur de transcription ICER-1 (Inductible cAMP Early Repressor-1). Ce puissant répresseur se fixe spécifiquement sur un motif CRE (cAMP Response Element), situé dans le promoteur du gène de la Cx36, inhibant ainsi son expression. Nous avons de plus démontré que des cytokines pro-inflammatoires, qui pourraient contribuer au développement du diabète, inhibent également l'expression de la Cx36. Cependant, les cytokines agissent indépendamment du répresseur ICER-1, mais selon un mécanisme requérant l'activation de l'AMPK (AMP dependant protein kinase). Sachant qu'un contrôle précis des niveaux d'expression de la Cx36 est un élément déterminant pour une sécrétion optimale de l'insuline, nos résultats suggèrent que la Cx36 pourrait être impliquée dans l'altération de la sécrétion de l'insuline contribuant à l'apparition du diabète de type 2. Summary A particular way by which cells communicate with each other is mediated by gap junctions, transmembrane structures providing a direct pathway for the diffusion of small molecules between adjacent cells. Gap junctional communication is required to maintain a proper functioning of insulin-secreting ß-cells. Moreover, the expression levels of connexin36 (Cx36), the sole gap junction protein expressed in ß-cells, are critical in maintaining glucose-stimulated insulin secretion. Chronic hyperglycemia and hyperlipidemia exert deleterious effects on insulin secretion and may contribute to the progressive ß-cell failure linked to the development of type 2 diabetes and metabolic syndrome. Since modulations of the Cx36 levels might impair ß-cell function, the general aim of this work was to elucidate wether elevated levels of glucose and lipids affect Cx36 expression. The first part of this work was dedicated to the study of the effect of high glucose concentrations on Cx36 expression. We demonstrated that glucose transcriptionally down-regulates the expression of Cx36 in insulin-secreting cells through activation of the protein kinase A (PKA), which in turn stimulates the expression of the inducible cAMP early repressor-1 (ICER-1). This repressor binds to a highly conserved cAMP response element (CRE) located in the Cx36 promoter, thereby inhibiting Cx36 expression. The second part of this thesis consisted in studying the effects of sustained exposure to free fatty acids (FFA) and human lipoproteins on Cx36 levels. The experiments revealed that the most abundant FFA, palmitate, as well as the atherogenic low density lipoproteins (LDL), also stimulate ICER-1 expression, resulting in Cx36 down-regulation. Finally, the third part of the work focused on the consequences of long-term exposure to proinflammatory cytokines on Cx36 content. Interleukin-1 ß (IL-1 ß) inhibits Cx36 expression and its effect is potentialized by tumor necrosis factor α (TNFα) and interferon γ (IFNγ). We further unveiled that the cytokines effect on Cx36 levels requires activation of the AMP dependent protein kinase (AMPK). Prolonged exposures to glucose, palmitate, LDL, and pro-inflammatory cytokines have all been proposed to contribute to the development of diabetes and metabolic syndrome. Since Cx36 expression levels are critical to maintain ß-cell function, Cx36 down-regulation by glucose, lipids, and cytokines might participate to the ß-cell failure associated with diabetes development.