De så kallade 3:12-reglerna tillkom i samband med 1990/91 års skattereform i syfte att reglera beskattningen för ägare av fåmansföretag. Det huvudsakliga syftet med reglerna är att förhindra fåmansföretagare från att ta ut utdelning istället för lön för att få skatteförmåner. Från början infördes stränga stoppregler för att i högsta möjliga grad förhindra inkomstomvandling. De stränga reglerna fick oönskade konsekvenser i form av minskad tillväxt i fåmansföretagen. För att öka företagandet och investeringsviljan blev reglerna med åren mer generösa och denna trend har fortsatt ända fram till införandet av de senaste ändringarna som trädde i kraft den 1 januari 2014. I första delen av uppsatsen visar vi bakgrunden till 3:12-reglerna, reglernas utveckling fram till idag samt redogör för skälen till införandet av reglerna och till de ändringar som gjorts. I analysen utreder vi huruvida lagstiftarens syfte med 3:12-reglerna kommer att uppnås i teorin med hjälp av de senaste ändringarna. Vi kommer fram till att en utformning av reglerna är en mycket komplex uppgift, där svårigheten ligger i en avvägning mellan att både gynna tillväxt i fåmansföretag, samtidigt som reglerna skall motverka inkomstomvandling. Vi kommer fram till att inkomstomvandling inte får förhindras på stor bekostnad av tillväxten. De ändringar som infördes den 1 januari 2014 tror vi skulle kunna resultera i nya sätt att inkomstomvandla samtidigt som tillväxten inte kommer att gynnas. Exempel på alternativa sätt att utforma reglerna finns även med i den analytiska delen av uppsatsen. För att lösa problematiken kring 3:12-reglerna föreslår vi ett enklare system där reglerna endast bör omfatta de mindre fåmansföretagen för att gynna tillväxt i högre mån. / The so-called 3:12-rules were introduced in connection with the tax reform in 1990/91 with the purpose to regulate the taxation for owners of closely held corporations (fåmansföretag). The main purpose of the rules is to prevent owners of closely held corporations from taking out dividend instead of wage to get tax benefits. From the beginning strict rules were introduced to minimize income-shifting. The strict rules resulted in undesirable consequences such as decreased growth in closely held corporations. Over the years, the rules got more generous in order to increase entrepreneurship and this trend has continued until the latest changes were introduced in 1st of January 2014. In the first part of this paper we elaborate on the background of the 3:12-rules and the development of the rules until today. We describe the motives for introducing the rules and the underling motives to the changes. In the analysis we investigate if the motives of 3:12-rules according to the lawmaker will be fulfilled with the help of the recently introduced changes. We conclude that the design of the rules is a complex task, whereas the difficulty lies in the consideration between both to benefit entrepreneurship and at the same time prevent income-shifting. We conclude that income-shifting cannot be prevented at the great expense of growth. We believe that the new changes that, introduced in the 1st of January 2014, could result in new ways to achieve income-shifting and will probably not drive growth. Examples of alternative ways to design the rules are included in our analysis. To solve the problematic situation regarding the 3:12-rules, we recommend a simpler system where the rules only include the smaller closely held corporations and promote growth to a greater extent.

Submitted by Automação e Estatística (sst@bczm.ufrn.br) on 2018-07-26T16:46:39Z No. of bitstreams: 1 LauraXimenaLovisa_TESE.pdf: 2713163 bytes, checksum: 72a30a3d8b6dfabe41949596578d2427 (MD5) / Approved for entry into archive by Arlan Eloi Leite Silva (eloihistoriador@yahoo.com.br) on 2018-07-26T19:02:52Z (GMT) No. of bitstreams: 1 LauraXimenaLovisa_TESE.pdf: 2713163 bytes, checksum: 72a30a3d8b6dfabe41949596578d2427 (MD5) / Made available in DSpace on 2018-07-26T19:02:52Z (GMT). No. of bitstreams: 1 LauraXimenaLovisa_TESE.pdf: 2713163 bytes, checksum: 72a30a3d8b6dfabe41949596578d2427 (MD5) Previous issue date: 2018-02-09 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / Uma nova classe de materiais inorgânicos, que surgem como uma opção promissora em aplicações de alto desempenho no campo da fotoluminescência, tem ganhado uma atenção especial. Este grupo é constituído pelos molibdatos, XMoO4 (X: íon metálico), dopados com elementos de terras raras (TR). As características que descrevem estes materiais são: alta eficiência luminosa, longo tempo de decaimento e apresentação de emissões no visível. Neste trabalho foram sintetizadas partículas de ZnMoO4 e a série ZnMoO4: 1% Tm+3 , 1% Tb+3, x Eu+3 (x = 1, 1.5, 2, 2.5 e 3%mola partir do método sonoquímico. Foram investigadas as influências causadas pelo teor dos dopantes e pelo tratamento térmico no comportamento fotoluminescente. Os resultados de difração de raios X confirmaram a formação da fase α- ZnMoO4 com estrutura cristalina triclínica para as partículas. Os valores da energia de gap estão na faixa de 3.58 e 4.22 eV. As imagens do MEV-FEG apresentam uma mudança na morfologia das partículas em conformidade com o aumento da dopagem. A morfologia das partículas foi interpretada com base em uma análise comparativa entre as imagens modeladas teoricamente e as experimentais de microscopia eletrônica de varredura de emissão de campo. Os cálculos de primeiro princípio em um nível de teoria funcional de densidade foram realizados para obter os valores de energias de superfície e estabilidade relativa das superfícies (120), (001), (011), (201) e (100) usando a construção de Wulff. Os resultados de fotoluminescência mostram as emissões específicas do Tb+3 e do Eu+3.Os valores das coordenadas de cromaticidade sofreram bastante influencia com aumento da temperatura de tratamento, exibindo emissão na região do amarelo – laranja, do verde e do branco. / A new class of inorganic materials, which emerge as a promising option in highperformance applications in the field of photoluminescence, has gained special attention. This group consists of the molybdates, XMoO4 (X: metal ion), doped with rare earth elements (RE). The characteristics that describe these materials are: high luminous efficiency, long decay time and emission presentation in the visible. In this work ZnMoO4 and ZnMoO4: 1% Tm3+, 1% Tb3+, x Eu3+ (x = 1, 1.5, 2, 2.5 and 3 mol%) particles were synthesized from the sonochemical method. The influence of dopant content and heat treatment on photoluminescent behavior was investigated. The X-ray diffraction results confirmed the formation of α- ZnMoO4 phase with triclinic crystalline structure for the particles. The values of the gap energy are in the range of 3.58 and 4.22 eV. The images of the FESEM show a change in particle morphology in accordance with increased doping. The morphology of the particles was interpreted based on a comparative analysis between the theoretically and experimentally modeled images of field emission scanning electron microscopy. First-principle calculations at a density functional theory level were performed to obtain the values of surface energies and relative stability of the (120), (001), (011), (201), and (100) surfaces by employing the Wulff construction. The results of photoluminescence clearly show the specific emissions of Tb3+ and Eu3+. The values of the chromaticity coordinates were influenced by the increase in the treatment temperature, showing emission in the yellowish orange, green and white regions.

Glycogen Synthase Kinase 3 (GSK3), a serine/threonine kinase initially characterized in the context of glycogen metabolism, has been repeatedly realized as a multitasking protein that can regulate numerous cellular events in both metazoa and protozoa. I recently found GSK3 plays a role in regulating chemotaxis, a guided cell movement in response to an external chemical gradient, in one of the best studied model systems for chemotaxis - Dictyostelium discoideum. It was initially found that comparing to wild type cells, gsk3- cells showed aberrant chemotaxis with a significant decrease in both speed and chemotactic indices. In Dictyostelium, phosphatidylinositol 3,4,5-triphosphate (PIP3) signaling is one of the best characterized pathways that regulate chemotaxis. Molecular analysis uncovered that gsk3- cells suffer from high basal level of PIP3, the product of PI3K. Upon chemoattractant cAMP stimulation, wild type cells displayed a transient increase in the level of PIP3. In contrast, gsk3- cells exhibited neither significant increase nor adaptation. On the other hand, no aberrant dynamic of phosphatase and tensin homolog (PTEN), which antagonizes PI3K function, was observed. Upon membrane localization of PI3K, PI3K become activated by Ras, which will in turn further facilitate membrane localization of PI3K in an F-Actin dependent manner. The gsk3- cells treated with F-Actin inhibitor Latrunculin-A showed no significant difference in the PIP3 level. I also showed GSK3 affected the phosphorylation level of the localization domain of PI3K1 (PI3K1-LD). PI3K1-LD proteins from gsk3- cells displayed less phosphorylation on serine residues compared to that from wild type cells. When the potential GSK3 phosphorylation sites of PI3K1-LD were substituted with aspartic acids (Phosphomimetic substitution), its membrane localization was suppressed in gsk3- cells. When these serine residues of PI3K1-LD were substituted with alanine, aberrantly high level of membrane localization of the PI3K1-LD was monitored in wild type cells. Wild type, phosphomimetic, and alanine substitution of PI3K1-LD fused with GFP proteins also displayed identical localization behavior as suggested by the cell fraction studies. Lastly, I identified that all three potential GSK3 phosphorylation sites on PI3K1-LD could be phosphorylated in vitro by GSK3.

A novel small molecule, 1-ethoxy-3-(3,4-methylenedioxyphenyl)-2-propanol (EOD), was synthesized in our laboratory. Previously, we reported pharmacological properties of EOD, triggering apoptosis in Human umbilical vein endothelial cells (HUVECs). Here, we further investigated the effects of EOD on the growth of A549 human lung cancer cells. EOD treatment induced apoptosis in A549 cells via up-regulating the expression of P53 protein, blocking cell cycle partly at G1 phase, and ultimately activating caspase-3. In contrast, caspase-8 might be irrelevant to EOD-triggered apoptosis. This study indicated that EOD might be a potential chemopreventive agent for lung cancer. The work would encourage us to add more novel compounds to our 'library' of small molecules derived through modern synthetic organic chemistry, and would drive us to determine the proteins that the compounds target.

Discrete optimization problems are defined by a finite set of solutions together with an objective function value assigned to each solution. Local search algorithms provide useful tools for addressing a wide variety of intractable discrete optimization problems. Each such algorithm offers a distinct set of rules to intelligently exploit the solution space with the hope of finding an optimal/near optimal solution using a reasonable amount of computing time. This research studies and analyses randomly generated instances of 3-SATISFIABILITY to gain insights into the structure of the underlying solution space. Two random variables are defined and analyzed to assess the probability that a fixed solution will be assigned a particular objective function value in a randomly generated instance of 3-SATISFIABILITY. Then, a random vector is defined and analyzed to investigate how the solutions in the solution space are distributed over their objective function values. These results are then used to define a stopping criterion for local search algorithms applied to MAX 3-SATISFIABILITY. This research also analyses and compares the effectiveness of two local search algorithms, tabu search and random restart local search, on MAX 3-SATISFIABILITY. Computational results with tabu search and random restart local search on randomly generated instances of 3-SATISFIABILITY are reported. These results suggest that, given a limited computing budget, tabu search offers an effective alternative to random restart local search. On the other hand, these two algorithms yield similar results in terms of the best solution found. The computational results also suggest that for randomly generated instances of 3-SATISFIABILITY (of the same size), the globally optimal solution objective function values are typically concentrated over a narrow range. / Ph. D.

Le motif 3-hydroxyoxindole est présent dans de nombreuses molécules biologiquement actives, qu’elles soient d’origine naturelle ou synthétique. Dans le cadre de cette thèse nous nous sommes intéressés aux différents aspects de la chimie associée à ce motif. Dans un premier temps, nous avons développé une nouvelle méthodologie très générale donnant accès à cet hétérocycle. En effet, une réaction de Friedel-Crafts cyclisante promue par l’acide trifluoroacétique permet d’obtenir des 3-hydroxy, 3-amino et 3-spirooxindoles diversement substitués à partir de cétoanilides non préfonctionnalisés. Dans un deuxième temps, nous avons commencé l’étude vers la synthèse de l’azonazine, qui fait intervenir un intermédiaire 3-hydroxyoxindole. L’étape clé de cette synthèse est la réaction de Friedel-Crafts cyclisante, développée dans la première partie. Le 3-hydroxyoxindole intermédiaire a été obtenu avec un bon rendement, illustrant notre méthodologie. Finalement, nous avons poursuivi l’étude vers la synthèse du TMC-95A, qui contient le motif 3-hydroxyoxindole, initiée précédemment dans notre laboratoire. Nous avons développé la voie de synthèse permettant d’accéder à la partie Nord, 3-hydroxyoxindole hautement fonctionnalisé de la molécule. L’étape clé est la synthèse du motif 3-hydroxoxindole à partir d’une isatine par addition d’un acide alcénylboronique catalysée au rhodium(I). / The 3-hydroxyoxindole motif can be found in many biologically active compounds, natural or man-made. In the context of this work, we got interested in the different aspects of the chemistry associated with this motif. First, we developed a new and very general methodology to access this heterocycle. Indeed, a cyclizing reaction of Friedel-Crafts promoted by trifluoroacetic acid gave us access to variously substituted 3-hydroxy, 3-amino and 3-spirooxindoles from non prefunctionalized ketoanilides. Then, we started studies towards the synthesis of azonazine, which involves a 3-hydroxyoxindole intermediate.The key step of this synthesis is the cyclizing reaction of Friedel-Crafts developed in the first part. The 3-hydroxyoxindole intermediate was obtained with a good yield, thus illustrating our methodology. Finally, we continued the studies towards the synthesis of TMC-95A, which contains the 3-hydroxyoxindole motif. We developed the synthetic pathway enabling us to access the Northern part of the molecule, a highly functionalized 3-hydroxyoxindole. The key step is the synthesis of the 3-hydroxyoxindole from an isatin by a rhodium(I)-catalyzed addition of an alkenylboronic acid.

Ce travail porte sur la réalisation de capteurs interdigités (IDT pour InterDigital Transducer) sur des supports piézoélectriques. L’enjeu est double puisqu’il s’agit premièrement de disposer de capteurs efficaces pour générer des ondes de surface acoustiques (SAW pour Surface Acoustic Wave) afin de caractériser la qualité des revêtements et des surfaces de structures. Le deuxième objectif de cette étude est de rendre ces capteurs IDT flexibles afin qu’ils puissent s’adapter non seulement aux différentes géométries planes ou non mais aussi pour qu’ils soient capables de supporter les déformations des structures au cours de leur utilisation. En général, les matériaux piézoélectriques sont rigides et le caractère souple des matériaux est souvent en opposition avec les performances piézoélectriques de ces derniers ; nous avons donc développé des matériaux qui répondent à ces deux exigences : la performance piézoélectrique et la souplesse. Enfin, nous avons privilégié des technologies relativement bon marché pour développer ces capteurs afin d’envisager par la suite, un contrôle continu des structures en intégrant ces capteurs à demeure sur ces dernières. / This work deals with the realization of interdigital sensors (IDT for InterDigital Transducer) on piezoelectric substrates. There is a dual challenge since firstly, the aim is to have efficient sensors to generate surface acoustic waves (SAW) in order to characterize the quality of the coatings and structure surfaces. The second objective of this study is to make these IDT sensors flexible so as to adapt to different geometries of structures and to be able to put up with the deformations of structures in use. Typically, piezoelectric materials are rigid and the flexible nature of the materials is often in opposition to the piezoelectric performance of the latter. We developed materials that meet these two requirements: piezoelectricity and flexibility. Finally, we gave greater importance to relatively cheap technologies to develop these sensors because this allows then to consider continuous monitoring (structural health monitoring) by incorporating these sensors permanently on the structures to be tested.

No description available.

Submitted by Fabio Sobreira Campos da Costa (fabio.sobreira@ufpe.br) on 2016-09-02T14:54:35Z No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) DISSERTAÇÃO - Alinny R Isaac - 2016.pdf: 2520039 bytes, checksum: 294508e64fe5208cfd8d2b48f9465be5 (MD5) / Made available in DSpace on 2016-09-02T14:54:35Z (GMT). No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) DISSERTAÇÃO - Alinny R Isaac - 2016.pdf: 2520039 bytes, checksum: 294508e64fe5208cfd8d2b48f9465be5 (MD5) Previous issue date: 2016-02-16 / CNPq / Ácidos graxos essenciais da família ômega-3 são cruciais durante o desenvolvimento cerebral atuando na transcrição gênica e sobre mecanismos epigenéticos, influenciando a gênese e diferenciação de neurônios e astrócitos. Por outro lado, evidências têm mostrado que a desnutrição materno-proteica pode modificar negativamente padrões epigenéticos do genoma fetal. O presente estudo investigou se uma razão ômega-6/ômega-3 (n-6/n-3) favorável na dieta materna pode influenciar alterações pós-traducionais em histonas de células neurais da prole, mesmo em uma condição de deficiência em proteínas e outros micronutrientes. Ratas Wistar foram mantidas em uma dieta com deficiência multifatorial (Dieta Básica Regional – DBR) possuindo, entretanto, uma baixa razão n-6/n-3 em relação a dieta controle, 30 dias antes do acasalamento e durante a gestação. Embriões de 16 dias de gestação e neonatos de 0 a 3 dias pós-natais foram utilizados para a realização de culturas corticais de neurônios e astrócitos, respectivamente. Acetilação de H3K9 e dimetilação de H3K4 e H3K27 foram avaliados por imunocitoquímica e citometria de fluxo. Análises por densitometria ótica mostraram aumento nos níveis de H3K4me2 nos astrócitos do grupo malnutrido (Mn) (27115±9892 P < 0.005) em relação ao grupo nutrido (N) (22583±6194) e nenhuma alteração nos níveis de H3K9Ac (Mn: 27401±10248 vs. N: 30034±10423) ou H3K27me2 (Mn: 16693±4842 vs. N: 16187 ±3378). Tratamento das culturas com um inibidor de histona acetiltransferase (HAT), promoveu uma redução da acetilação de maneira dose dependente menor nos astrócitos do grupo malnutrido em relação ao nutrido. Através de análises por citometria de fluxo não observaram-se diferenças entre as grupos (H3K9Ac - Mn: 13217± 6821 vs. N:14620± 6515 / H3K4me2 - Mn: 22917± 14938 vs. N: 25956± 14258). Por outro lado, o tratamento dos astrócitos por 24 horas com 100μM de DHA promoveu um aumento de 60% na acetilação de H3K9 do grupo malnutrido. Análise de western blot para GFAP mostrou que ambos os grupos apresentam a expressão predominante da isoforma fosforilada desta proteína com 50kDa. Imunocitoquímica para H3K9Ac em neurônios mostrou um aumento nos níveis de fluorescência no grupo malnutrido (Mn: 30107±6789 vs. N: 25257±7562, P = 0.0075), e nenhuma diferença entre os grupos em relação à H3K4me2 (Mn: 23203±7059 vs. N: 22654± 5376). Não houve ativação do fator de transcrição gênica NK-kB nestas células. O perfil de ácidos graxos do leite materno no estômago dos neonatos foi avaliado por cromatografia gasosa, mostrando que a razão ácido linoleico/ácido alfa-linolênico da DBR é mantida. H3K9Ac e H3K4me2 estão envolvidos no aumento da transcrição de genes relacionados à gênese e diferenciação de astrócitos e neurônios. Nossos resultados indicam uma possível relação entre a razão favorável de n-6/n-3 presente na DBR sobre a promoção da transcrição gênica, mesmo em um contexto de baixa proteína. Além disso, sugere-se que o DHA esteja atuando sobre a acetilação, mantendo-a estável, em função da sua influência sobre as enzimas que atuam nesse processo. / Omega-3 essential fatty acids play key roles during brain development acting on gene transcription and epigenetic mechanisms influencing the genesis and differentiation of neurons and astrocytes. On the other hand, evidence has shown that maternal protein malnutrition may negatively change epigenetic patterns of the fetal genome. The present study investigated whether a low and favorable ômega-6/ômega-3 (n-6/n-3) ratio on maternal diet may induce histone post-translational changes in neural cells of the offspring, even in a condition of protein and micronutrients deficiency. Wistar rats were maintained on a diet with multifactorial deficiency (Regional Basic Diet-RBD) containing, however, a low n-6/n-3 ratio compared to the control diet, 30 days prior to mating and during gestation. Embryos of 16 days and newborns from 0 to 3 postnatal days were used to obtain cortical neuron and astrocyte primary cultures, respectively. Acetylation of H3K9 and dimethylation of H3K4 and H3K27 were evaluated by flow cytometry and immunocytochemistry. The results of optical density showed increased levels of H3K4me2 in astrocytes of the malnourished group (Mn) (27115 ± 9892; P <0.005) when compared to the nourished group (N) (22583 ± 6194). On the other hand, no change in the H3K9Ac (Mn: 27401 ± 10248 vs. N: 30034 ± 10423) or H3K27me2 (Mn: 16693 ± 4842 vs. N: 16187 ± 3378) were observed. Treatment of astrocyte cultures with an inhibitor of histone acetyltransferase (HAT), was able to decrease acetylation in a dose-dependent manner; however, this decay was less intense in astrocytes of the malnourished group compared to the nourished. Through analysis by flow cytometry no intergroup differences (H3K9Ac - Mn: 13217± 6821 vs. N: 14620 ± 6515 / H3K4me2 - Mn: 22917± 14938 vs. N: 25956± 14258). On the other hand, the treatment of astrocytes by 24 h with 100 μM DHA increased ~60% H3K9 acetylation levels of astrocytes in the malnourished group. Western blot analysis for GFAP showed in both groups the predominant expression of the phosphorylated isoform with 50 kDa. Immunocytochemistry for H3K9Ac and H3K4me2 in neurons indicated an increase in the levels of H3K9Ac fluorescence in the malnourished group (Mn: 30107 ± 6789 vs. N: 25257 ± 7562, P=0.0075) and no intergroup difference in the H3K4me2 (Mn: 23203 ± 7059 vs. N: 22654 ± 5376). No activation of the transcription factor NK-kB gene was found in these cells. The fatty acid profile of the breast milk in the stomach of newborns was evaluated by gas chromatography, showing that the linoleic/alpha-linolenic ratio present in the RBD is maintained. H3K9ac and H3K4me2 are involved in the increased transcription of genes related to the genesis and differentiation of astrocytes and neurons. In this way, the results obtained in this study points to a possible contribution of low n-6/n-3 present in the RBD on promotion of gene transcription, even in a context of low protein. In addition, it is suggested that DHA is acting on the acetylation, keeping it stable, probably due a potential influence on the enzymes involved in this process.

L’arthrose est la pathologie articulaire la plus fréquente, caractérisée par une destruction progressive du cartilage articulaire et impliquant une communication anormale entre l'os sous-chondral et le cartilage. Notre équipe a identifié la protéine 14-3-3ε comme un médiateur soluble secrété par l’os et capable d’altérer l'homéostasie du cartilage en stimulant l’expression de MMP-3 et MMP-13, deux métalloprotéases impliquées dans la dégradation du cartilage au cours de l’arthrose. CD13/APN, récepteur potentiel pour cette protéine, a été mis en évidence à la surface des chondrocytes murins et humains. Le but de cette étude était d’étudier son implication dans la réponse des chondrocytes à 14-3-3ε. L’invalidation de CD13/APN par des siRNA ou des anticorps bloquants, réduit significativement l’effet catabolique chondrocytaire induit par 14-3-3ε. Les chondrocytes articulaires possèdent une activité APN mais elle n’est pas modifiée en présence de 14-3-3ε. Nous avons mis en évidence la présence d’une interaction directe entre 14-3-3ε et CD13/APN grâce à la technologie SPR (Surface Plasmon Resonance) et le système Biacore. En utilisant 14-3-3ε marquée à la biotine, nous avons montré que 14-3-3ε est capable de se lier à la surface des chondrocytes via CD13/APN. Nous avons donc eu recours ensuite aux études de modélisation in silico qui ont permis d’identifier le résidu Y582 phosphorylé appartenant à la séquence E579FNYVW584 de CD13/APN, comme résidu indispensable pour sa liaison à 14-3-3ε. Ce travail de thèse permet de mieux comprendre le mécanisme d’action de 14-3-3ε et propose l’interaction entre 14-3-3ε et CD13 comme une nouvelle cible thérapeutique dans l’arthrose. / Osteoarthritis (OA) is a whole-joint disease characterized by progressive destruction of articular cartilage involving abnormal communication between subchondral bone and cartilage. Our team identified 14-3-3ε protein as a subchondral bone soluble mediator altering cartilage homeostasis. This protein acts as a potent stimulatory factor of MMP-3 and MMP-13 involved in the degradation of cartilage matrix in OA. CD13/APN, potential receptor of this protein, was identified on the surface of chondrocytes. The aim of this study was to investigate its involvement in chondrocytes response to 14-3-3ε. CD13/APN invalidation, using the siRNA strategy and blocking antibodies, reduces significantly the catabolic effect induced by 14-3-3ε in chondrocytes. APN activity was identified in chondrocytes but found unchanged following stimulation with 14-3-3ε. Then, we have revealed the presence of a direct interaction between 14-3-3ε and CD13/APN through the SPR (Surface Plasmon Resonance) and the Biacore system. Using biotin-labeled 14-3-3ε, we have shown that 14-3-3ε is able to bind to the surface of chondrocytes in a manner that is dependent on CD13/APN. It was then necessary to identify the putative motifs involved in this interaction. We therefore used in silico modelling studies which have identified the phosphorylated residue Y582, belonging to the E579FNYVW584 sequence of CD13/APN, as a critical residue for its binding to 14-3-3ε. This thesis work suggest that CD13 plays its receptor role to bind 14-3-3ε and transmit its signal in chondrocytes to induce a catabolic phenotype similar to that observed in OA. Thus, 14-3-3ε-CD13 interaction could be a novel therapeutic target in OA.