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Introdução: A obesidade, doença crônica e multifatorial, decorre de uma predisposição genética associada a fatores ambientais e ao desequilíbrio energético. A taxa metabólica de repouso (TMR) representa o principal componente do gasto energético e está diretamente relacionada à massa livre de gordura. A participação do tecido adiposo marrom na regulação do gasto energético em adultos tem sido avaliada nos últimos anos. Em 2012, um hormônio denominado irisina foi descrito participar deste processo através da indução de uma subpopulação de adipócitos brancos em um subtipo nomeado bege, com características funcionais semelhantes ao marrom. Em roedores, este hormônio foi associado ao aumento da termogênese, redução do peso corporal e melhora do perfil glicêmico. Em humanos, entretanto, sua contribuição para a regulação energética bem como seu envolvimento em distúrbios metabólicos permanece incerto. Objetivos: Esta tese é composta de dois estudos originais. O primeiro avaliou os níveis de irisina em pacientes com diferentes categorias de índice de massa corporal (IMC), bem como sua associação com parâmetros antropométricos, metabólicos e de composição corporal. Além disso, foram comparados os níveis de irisina nos pacientes após perda de peso induzida cirurgicamente a controles obesos. Já o segundo artigo, teve como objetivo avaliar as mudanças na TMR conforme as modificações da composição corporal após cirurgia bariátrica e a influência da TMR sobre o excesso de peso perdido em 12 e 18 meses. Métodos: O primeiro artigo foi uma coorte prospectiva e o segundo, um estudo observacional prospectivo. Pacientes com idade superior a 18 anos foram avaliados entre 2013 a 2015. Para avaliação da irisina plasmática, 77 pacientes foram classificados conforme o seu IMC nos seguintes grupos: Grupo 1: IMC entre 18,5 a 27 kg/m², n = 11; Grupo 2: IMC entre 30 kg/m² a 39,9 kg/m², n = 36 e Grupo 3: IMC maior ou igual a 40 kg/m², n = 30. Os pacientes dos Grupos 1 e 2 foram submetidos a qualquer cirurgia abdominal eletiva, exceto cirurgia bariátrica e os pacientes do Grupo 3 ao bypass gástrico em Y de Roux. Os 3 grupos foram avaliados no basal e os Grupos 2 e 3 foram reavaliados em 6 meses. Já para avaliação da TMR após a perda de peso induzida pela cirurgia bariátrica, 30 pacientes foram avaliados imediatamente antes e após 6 meses da cirurgia. A TMR foi avaliada por calorimetria indireta, a composição corporal pela absorciometria por raio X com dupla energia e os níveis plasmáticos de irisina por kit Elisa (Phoenix Pharmaceuticals). Resultados: A maioria dos pacientes avaliados em ambos os estudos foi composta de mulheres (80%), brancos (82%), e com média de idade de 46±14 anos. Em relação ao estudo sobre irisina, no basal, os pacientes do Grupo 3 apresentaram mediana de irisina menor em relação ao Grupo 2: 8,4 (7,8 – 10,5) vs 9,9 (8,9 – 12,0) ng/ml, respectivamente; P = 0,014. Uma correlação inversa foi observada entre os níveis de irisina e o peso corporal (r = -0,246; P = 0,042), circunferência da cintura (r = -0,272; P = 0,024), glicemia de jejum (r = -0,259; P = 0,039), hemoglobina glicada (r = -0,283 P = 0,024), e triglicerídeos (r = -0,414 P <0,001). Os níveis de irisina foram positivamente correlacionados ao HDL (r = 0,280; P = 0,029). Em 6 meses, todas as medidas antropométricas e de composição corporal foram similares, exceto pela menor TMR corrigida para o peso (P = 0,038) e para massa livre de gordura (P = 0,044), e os níveis de irisina, que permaneceram menores nos pacientes do Grupo 3 (P = 0,006). Dos 30 pacientes avaliados no segundo estudo, a média de IMC foi de 49 ± 9 kg/m², peso corporal de 128 ± 19 kg, metade do qual constituído por massa gorda (50 ± 5%). A TMR no basal foi 2297 ± 182 kcal/dia. O excesso de peso perdido foi de 54 ± 16%, sendo 45% como massa gorda e 24% como massa livre de gordura. A TMR reduziu 19% durante o seguimento (-405 ± 108 kcal/dia; P <0,001). Pacientes com uma redução superior a 405 kcal/dia em 6 meses apresentaram menor excesso de peso perdido em 18 meses (r = -0,612; P = 0,035). Conclusão: Os níveis de irisina estão reduzidos nos pacientes com obesidade grau 3 (IMC ≥40 kg/m²), bem como os níveis de irisina mostraram uma correlação inversa com parâmetros metabólicos relacionados à ação da insulina, sugerindo um provável envolvimento deste hormônio em estados de resistência insulínica, como a obesidade e o diabetes tipo 2. Além disso, pacientes submetidos à cirurgia bariátrica que apresentaram uma maior redução na TMR em 6 meses exibiram um menor excesso de peso perdido em longo prazo.

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Les rhabdomyosarcomes embryonnaires et aléolaires (RMS) appartiennent aux tumeurs des tissus mous les plus fréquentes chez les enfants dont elles représentent 2/3 des cas. Plusieurs données suggèrent que la dérégulation des cellules progénitrices du muscle squelettique pourrait jouer un rôle dans l'émergence des cellules de RMS qui ont aussi bien perdu le contrôle de la régulation de la prolifération cellulaire que la capacité à se différencier.Néanmoins les mécanismes de développement des RMS restent à caractériser. La famille des IMPs et notamment IMP-2, protéines liant les ARN, sont à la fois fortement exprimées dans le muscle en régénération in vivo mais aussi dans les cellules de RMS.Au cours de ma thèse, j’ai pu mettre en évidence le rôle d’IMP-2 dans la motilité des cellules de RMS et dans les cellules musculaires ainsi que dans le contrôle de l’intégrité du cytosquelette de microtubules (MTs) et dans le remodelage des adhésions focales. En effet, IMP-2 est impliqué à la fois dans la régulation de l’expression de MuRF-3, une protéine lié àla stabilisation des MTs et de Pinch-2, un important médiateur de l’adhésion cellulaire. / The RNA-binding proteins IMPs (IGF-II mRNA binding protein) first discovered in rhabdomyosarcoma cells (RMS) are expressed during embryonic development but their expression is decreased in adult tissues.We showed that IMPs and particularly IMP-2 are strongly expressed in mouse myoblatsts, during early regeneration of skeletal muscle in vivo and in and RMS. IMP-2 loss of function experiments using siRNA have shown that IMP-2 is necessary for microtubules stability(MTs), cell motility and invasion of myoblasts and RMS.Expression of IMP-2 specifically increases MTs stability by an enrichment of detyrosinated tubulin Glu-tubulin. Detyrosination is indispensable for myogenic differentiation and plays substantial role in tumor growth. Additionaly, MTs stabilization play an important role in focal adhesion remodeling, in cytoskeleton integrity, cell adhesion and cell motility.To get new insight into molecular mechanism underlying the function of IMP-2 in MTs stability and cell motility, full ranscriptome analysis was performed between IMP-2 knockdown (KD) myoblasts and control myoblatsts. We have further shown that IMP-2 controls the mRNA levels of many important mediators of cell adhesion such as PINCH-2, as well as multiple cytoskeleton remodeling, such as MuRF-3.We have identified a number of functionally relevant protein partners of IMP-2.Moreover subsequent RNAi screens have revealed the importance of IMP-2 regulated transcripts involved in cell motility and cell adhesion In conclusion, we show that IMP-2 dependent regulation of mRNA such as MuRF3 and PINCH2 largely contributes to the motility –deficient in IMP-2 KD cells. Moreover these results indicate clearly, that further analysis of IMP2 protein partners and RNA targets regulated by IMP-2 will help to characterized the function of IMP-2 and to propose a model of IMP-2 transcriptional regulation of gene expression in myoblasts and RMS cells.

Apparu dans un contexte de relative stabilité, le contrôle de gestion n’est plus adapté dans les environnements actuels caractérisés par une complexification croissante. Face à ces évolutions, un outil, le balanced scorecard (BSC) de Kaplan et Norton, présenté comme modèle à visée stratégique et non plus seulement financière, a réalisé une percée spectaculaire à travers le monde. Le but de cette recherche est de procéder à un examen des facteurs pouvant expliquer l’adoption du BSC par les entreprises françaises dans le cadre des tentatives contemporaines de renouvellement du contrôle de gestion. Suite au bilan de littérature sur le BSC, à l’identification des principales remises en cause du contrôle de gestion et à l’examen de certaines réponses proposées à celles-ci, une consultation a été menée auprès de 1623 entreprises, afin de mieux comprendre les raisons de l’adoption de cet outil de gestion. L’étude identifie ainsi les principales caractéristiques des utilisateurs du BSC en fonction de critères mobilisant la théorie de la contingence. Cette recherche offre la particularité de s’inspirer de la matrice de Løwendahl et Revang différenciant contexte externe/interne en s’intéressant aux adaptations de l’outil en fonction de la complexité. Des liens ont été observés en fonction du niveau d’utilisation du BSC, son contenu et les niveaux de complexité. L’étude permet de mieux comprendre pourquoi les entreprises adoptent, abandonnent ou ne mettent pas en œuvre le BSC dans notre contexte. Enfin, elle fournit également quelques informations sur les rôles des contrôleurs de gestion dans cet outil par rapport au tableau de bord français ou en fonction de la complexité. / Emerged in a context of relative stability, the management control is no longer appropriate in today's environment characterized by increasing complexity. Light of these developments, a tool, the balanced scorecard (BSC) of Kaplan and Norton presented as a model for strategic focus and not just financial, achieved a major breakthrough in the world. The purpose of this research is to conduct a review of the factors that may explain the adoption of the BSC by French companies in the context of contemporary attempts to renew the management control. After the review of literature on the BSC, the identification of the main challenges to the management control and examination of some proposed answers to these, a consultation was conducted among 1623 companies to better understand the reasons for the adoption of this management tool. The study identifies the main characteristics of BSC users based on criteria mobilizing contingency theory. This research offers the characteristic to be inspired of the matrix of Løwendahl and Revang which distinguishing external/internal environments and by focusing on the adaptations of the tool depending on the complexity. Linkages were observed depending on the level of use of BSC, its contents and levels of complexity. The study provides a better understanding of why companies adopt, abandon or not implement the BSC in our context. Finally, it also provides some information on the roles of management controllers in this tool relative to the French dashboard or depending on the complexity.

De nombreux acteurs sont de plus en plus attentifs aux comportements problématiques des consommateurs en matière budgétaire et financière. Les modèles de changement de comportement peuvent aider à l’élaboration de messages et d’approches adaptés dans ce domaine. Cette recherche montre que les stratégies de changement utilisées par le consommateur sont fondamentalement des stratégies d’approche et d’évitement et propose un modèle définissant le rôle de la balance décisionnelle dans l’utilisation de ces stratégies. Le modèle intègre également des variables individuelles telles que l’attitude à l’égard de l’argent et le niveau d’anxiété susceptibles de jouer sur l’adoption de ces stratégies. Ce modèle est appliqué à des groupes constitués de consommateurs en situations similaires sur la trajectoire du changement. Les dimensions de changement du modèle transthéorique (précontemplation, contemplation, action, maintien) ont servi de base à la construction de ces groupes. Les résultats montrent aussi les effets de l’orientation paratélique du consommateur. Les contributions théoriques concernent principalement l’explication de l’adoption de stratégies de changement de comportement financier de type approche-évitement. Les contributions managériales correspondent aux actions destinées à favoriser le changement en considérant plusieurs variables de segmentation et en particulier la situation des consommateurs sur leurs trajectoires de changement. / Increasing attention is being given by researchers, practitioners and stakeholders to issues raised by consumers’ financial and budgetary behavior. Models of behavior change can help develop messages and adapted approaches in this area. This research shows that strategies of change used by the consumer are basically approach and avoidance strategies and proposes a model defining the role of decisional balance in using of these strategies. The model also includes individual variables such as attitude towards money and anxiety level that may have influenced the adoption of these strategies. This model is applied to groups of consumers in similar situations in the trajectory of change. The dimensions of the transtheoretical model of change (precontemplation, contemplation, action, maintenance) has been used to obtain these groups. The results also show effects of consumer's paratelic orientation. Theoretical contributions mainly explain the adoption of approach-avoidance strategies of financial behavior change. Managerial contributions correspond to actions to promote change by considering several variables of segmentation in particular the position of consumers on their trajectory of change.

De nombreuses recherches en psychologie cognitive et en marketing ont tenté de comprendre la réaction du consommateur à une publicité contre-attitudinale. La littérature est dominée par deux courants. Le premier est focalisé sur la réaction des individus à partir des modèles sociocognitifs, tandis que le deuxième, moins développé, est concentré sur les inférences publicitaires développées par le consommateur suite à une tentative de persuasion. La majorité des travaux antérieurs ne prennent en considération qu’une infime partie du système motivationnel pour justifier la réaction des individus aux messages contre-attitudinaux. La revue de littérature met en évidence l’importance de mobiliser la théorie de l’orientation régulatrice afin de mieux cerner le traitement de l’information contre-attitudinale par le consommateur. Dans ce sens, le modèle conceptuel ainsi que les hypothèses ont été développés et testés empiriquement sur un échantillon de 190 consommateurs. Les résultats de cette démarche ont dénoté l’impact des orientations régulatrices des messages et des individus sur le traitement de l’information contre-attitudinale. La congruence entre les deux facettes de l’orientation régulatrice n’a permis d’améliorer l’efficacité de la persuasion que dans le cas des messages orientés promotion. De plus, les analyses ont permis de réaffirmer le rôle prépondérant de l’engagement affectif qui déclenche une motivation défensive et renforce la résistance du consommateur à la persuasion sur une marque concurrente. Les implications académiques et managériales ont été développées et plusieurs voies de recherche sont proposées. / Many studies in cognitive psychology and marketing have tried to understand consumer reaction to counterattitudinal advertising. The literature is dominated by two streams. The first focused on the response of individuals from socio-cognitive models, while the second, less developed, focused on advertising inferences developed by the consumer following an attempt at persuasion. Most previous studies only consider a fraction of the motivational system to justify the reaction of individuals to counterattitudinal messages . The literature review highlights the importance of mobilizing the theory of regulatory focus to better understand the processing of counterattitudinal information by the consumer. In this sense, the conceptual model and hypotheses were developed and empirically tested on a sample of 190 consumers. The results of this approach have denoted the impact of regulatory focus of messages and self-regulatory focus on the processing of counterattitudinal information. Congruence between the two facets of the regulatory focus has improved the effeciency of the persuasion only in the case of promotion oriented messages. Furthermore, analysis have reaffirmed the role of affective commitment that triggers a defensive motivation and strengthens consumer resistance to persuasion on a competing brand. Academic and managerial implications were developed and several lines of research are proposed.

The Bcl-2 family of proteins strictly regulates the intrinsic pathway of apoptosis. Direct physical interactions between Bcl-2 proteins regulate mitochondrial outerpermeabilisation (MOMP), which occurs in response to various cell stresses andapoptotic stimuli. How changes in Bcl-2 protein activity regulate apoptosiscommitment is still unclear, especially with regard to how they interact with eachother within the context of the mitochondrial membrane. Recent studies haveshown that Bcl-2 proteins exist in a dynamic equilibrium between the mitochondriaand the cytosol. In this thesis, by using FRAP, I have measured changes in Bcl-XLand Mcl-1 dynamics in single cells. Surprisingly, individual cells within a populationshow widely differing Bcl-XL and Mcl-1 dynamics. There is a corelation betweenBcl-XL and Mcl-1 dynamics with BH3-only protein expression. Anti-apoptotic andpro-apoptotic Bcl-2 proteins stabilise each other on the OMM. Together, theseresults indicate that cells constantly fine tune mitochondrial priming and thatanalysing anti-apoptotic Bcl-2 proteins by FRAP allows this to be measured at asingle cell level in real time before MOMP.

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Yip Mei Po. / "April 2002." / Thesis (Ph.D.)--Chinese University of Hong Kong, 2002. / Includes bibliographical references (p. 170-197). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Mode of access: World Wide Web. / Abstracts in English and Chinese.