Os ésteres de ftalato (PAEs) são compostos produzidos em grandes quantidades, amplamente utilizados industrialmente como agentes plastificantes. Seus resíduos são lixiviados pela água tornando-se poluentes orgânicos persistentes (POPs) no meio ambiente aquoso, além de apresentar características de interferência endócrina. O dietil ftalato (DEP) é frequentemente encontrado nas amostras ambientais, pois possui elevada solubilidade na água e pode ser gerado durante a degradação de outros PAEs. Assim, este trabalho teve como objetivo a degradação do dietil ftalato em meio aquoso por método eletroquímico utilizando um ânodo dimensionalmente estável (ADE) comercial representado como Ti/Ru0,3Ti0,7O2 em uma célula do tipo filtro-prensa. As eletrólises foram de 120 minutos contendo uma concentração inicial de 100,3 mg L-1 de DEP, pH inicial igual a 3, a temperatura em 25 °C e vazão em 250 mL min-1. Os experimentos foram feitos utilizando planejamento fatorial do tipo 32 com duas réplicas no ponto central, apresentando como variáveis independentes a densidade de corrente (10, 25 e 40 mA cm-2) e o logaritmo em base 10 da forca iônica do eletrólito suporte, NaCl e Na2SO4 (µ = 0,05, 0,15 e 0,5 mol L-1), com o intuito de estudar o efeito da densidade de corrente, concentração e natureza do eletrólito para determinar a melhor condição de degradação do dietil ftalato. O monitoramento da concentração do DEP foi feito com cromatografia líquida de alta eficiência (CLAE) e a mineralização foi acompanhada pelas análises de carbono orgânico total (COT). Foram obtidas maiores porcentagens de remoção e mineralização com uso das maiores densidades de corrente e na presença de altas concentrações de NaCl em comparação com Na2SO4. Dessa maneira, se obteve remoção de 63,2 % e mineralização de 63,9 % em solução 0,5 mol L-1 NaCl e densidade de corrente de 40 mA cm-2, enquanto que para Na2SO4 (µ = 0,5 mol L-1) e 40 mA cm-2 foi removido 51,3 % e mineralizado 53,0 % de DEP. O mecanismo de degradação de DEP foi determinado em meio de NaCl e Na2SO4, através de CLAE-MS nas condições citadas anteriormente, identificando-se os íons moleculares de m/z 149 e 177 em ambos eletrólitos, correspondentes ao anidrido ftálico protonado e ao aduto do anidrido ftálico com C(2)H(5)(+) respectivamente, íons característicos da fragmentação do DEP, além do íon m/z 239 em Na2SO4 correspondente ao dietil 3-hidroxiftalato. A degradação do DEP acontece através da cadeia alifática. / Phthalate esters (PAEs) are compounds produced in large amounts industrially widely used as plasticizers. Their waste are leached by water becoming persistent organic pollutants (POPs) in the aqueous environment, besides having endocrine disrupting characteristics. Diethyl phthalate (DEP) is frequently found in environmental samples, it has high solubility in water and can be generated during the degradation of other PAEs. This work studied the degradation of diethyl phthalate in aqueous media by electrochemical method using a commercial dimensionally stable anode (ADE) represented as Ti/Ru0,3Ti0,7O2 in a filter-press flow cell. The electrolysis were carried out during 120 minutes containing an initial concentration of 100.3 mg L-1 DEP, initial pH = 3, temperature at 25 °C and flow rate of 250 ml min-1. The experiments were performed using factorial design 32 with two replicas at the midpoint, with as independent variables the current density (10, 25 and 40 mA cm-2) and the logarithm base 10 of the ionic strength of the electrolyte, NaCl and Na2SO4 (µ = 0.05, 0.15 and 0.5 mol L-1), in order to study the effect of current density, concentration and nature of the electrolyte to determine the best diethyl phthalate degradation condition. The monitoring of DEP concentration was made by high-performance liquid chromatography (HPLC) and the mineralization was accompanied by total organic carbon (TOC) analysis. They obtained higher percentages of removal and mineralization with the use of higher current densities and in the presence of high concentrations of NaCl in comparison with Na2SO4. Thus, there was obtained the removal of 63.2 % and 63.9 % mineralization in 0.5 mol L-1 NaCl and current density of 40 mA cm-2, whereas for Na2SO4 (µ = 0.5 mol L-1) and 40 mA cm-2 was removed 51.3 % and 53.0% mineralized DEP. The DEP degradation mechanism was determined in NaCl and Na2SO4, by HPLC-MS under the conditions mentioned above, identifying the molecular ion of m/z 149 and 177 on both electrolytes, corresponding to protonated phthalic anhydride and an adduct of phthalic anhydride with C(2)H(5)(+), respectively, characteristic ions of DEP fragmentation, besides the ion m/z 239 over Na2SO4 corresponding to diethyl 3-hydroxyphthalate. The DEP degradation takes place through the aliphatic chain.

L’implication des protéines tyrosines phosphatases (PTPs) dans la régulation de la signalisation et la médiation des fonctions cellulaires a été bien établie dans les dernières années. Cependant, les mécanismes moléculaires par lesquels les PTPs régulent les processus fondamentaux tels que l’angiogenèse demeurent méconnus. Il a été rapporté que l’expression de la PTP DEP-1 (Density-enhanced phosphatase 1) augmente avec la densité cellulaire et corrèle avec la déphosphorylation du récepteur VEGFR2. Cette déphosphorylation contribue à l’inhibition de contact dans les cellules endothéliales à confluence et diminue l’activité du VEGFR2 en déphosphorylant spécifiquement ses résidus catalytiques Y1054/1059. De plus, la plupart des voies de signalisation en aval du VEGFR2 sont diminuées sauf la voie Src-Gab1-AKT. DEP-1 déphosphoryle la Y529 de Src et contribue à la promotion de la survie dans les cellules endothéliales. L’objectif de cette thèse est de mieux définir le rôle de DEP-1 dans la régulation de l’activité de Src et les réponses biologiques dans les cellules endothéliales. Nous avons identifié les résidus Y1311 et Y1320 dans la queue C-terminale de DEP-1 comme sites majeurs de phosphorylation en réponse au VEGF. La phosphorylation de ces résidus est requise pour l’activation de Src et médie le remodelage des jonctions cellules-cellules dépendantes de Src. Ce remodelage induit la perméabilité, l’invasion et la formation de capillaires en réponse au VEGF. Nos résultats démontrent que la phosphorylation de DEP-1 sur résidu tyrosine est requise pour diriger la spécificité de DEP-1 vers son substrat Src. Les travaux révèlent pour la première fois un rôle positif de DEP-1 sur l’induction du programme angiogénique des cellules endothéliales. En plus de la phosphorylation sur tyrosine, DEP-1 est constitutivement phosphorylé sur la thréonine 1318 situé à proximité de la Y1320 en C-terminal. Cette localisation de la T1318 suggère que ce résidu pourrait être impliqué dans la régulation de la Y1320. En effet, nous avons observé que la T1318 de DEP-1 est phosphorylée potentiellement par CK2, et que cette phosphorylation régule la phosphorylation de DEP-1 sur tyrosine et sa capacité de lier et d’activer Src. En accord avec ces résultats, nos travaux révèlent que la surexpression du mutant DEP-1 T1318A diminue le remodelage des jonctions cellules-cellules et par conséquent la perméabilité. Nos résultats suggèrent donc que la T1318 de DEP-1 constitue un nouveau mécanisme de contrôle de la phosphorylation sur tyrosine et que ceci résulte en l’activation de Src et l’induction des fonctions biologiques des cellules endothéliales en réponse au VEGF. Suite à ces travaux dans les cellules endothéliales qui démontrent un rôle positif de DEP-1 dans la médiation des réponses angiogéniques, nous avons voulu approfondir nos connaissances sur l’implication potentielle de DEP-1 dans les cellules cancéreuses où l’activité de Src est requise pour la progression tumorale. Malgré le rôle connu de DEP-1 comme suppresseur tumoral dans différents types de cancer, nous avons émis l’hypothèse que DEP-1 pourrait promouvoir les fonctions biologiques dépendantes de Src telles que la migration et l’invasion dans les cellules cancéreuses. Ainsi, nous avons observé que l’expression de DEP-1 est plus élevée dans les lignées basales de cancer du sein qui sont plus invasives comparativement aux lignées luminales peu invasives. Dans les lignées basales, DEP-1 active Src, médie la motilité cellulaire dépendante de Src et régule la localisation des protéines impliquées dans l’organisation du cytosquelette. L’analyse d’un micro-étalage de tissu a révélé que l’expression de DEP-1 est associée avec une réduction tendencielle de survie des patients. Nos résultats proposent donc, un rôle de promoteur tumoral pour DEP-1 dans la progression du cancer du sein. Les travaux présentés dans cette thèse démontrent pour la première fois que DEP-1 peut agir comme promoteur des réponses angiogéniques et du phénotype pro-invasif des lignées basales du cancer du sein probablement du à sa capacité d’activer Src. Nos résultats suggèrent ainsi que l’expression de DEP-1 pourrait contribuer à la progression tumorale et la formation de métastases. Ces découvertes laissent donc entrevoir que DEP-1 représente une nouvelle cible thérapeutique potentielle pour contrer l’angiogenèse et le développement du cancer. / The implication of protein tyrosine phosphatases (PTPs) in the regulation of cell signalling events and the mediation of cellular functions in response to growth factors such as VEGF has been well-established in the last years. Nonetheless, molecular mechanisms by which PTPs regulate fundamental processes such as angiogenesis are not well-characterized. Expression of the PTP DEP-1 (Density-enhanced phosphatase 1) was reported to increase with cell density and was associated with VEGFR2 dephosphorylation contributing to cell contact inhibition in confluent endothelial cells. We previously demonstrated that DEP-1 attenuates VEGFR2 activity by dephosphorylation of its Y1054/1059 leading to decreased activation of major signalling pathways downstream of VEGFR2 with exception of the Src-Gab1-AKT pathway. Increasing Src activity due to DEP-1-mediated dephosphorylation of its Y529 promotes endothelial cell survival. The objective of this thesis was to gain a better understanding of the role of DEP-1 in the regulation of the Src activity and of biological responses in endothelial cells. We identified tyrosine Y1311 and Y1320 in the C-terminal tail of DEP-1 as major phosphorylation sites in response to VEGF. These residues are required for Src activation and mediate the Src-dependent remodelling of endothelial cell junctions inducing permeability, invasion and capillary formation upon VEGF stimulation. We showed that VEGF-induced DEP-1 tyrosine phosphorylation directs DEP-1 specificity towards its substrate Src. Our results thus highlighted for the first time the promoting role of DEP-1 on the angiogenic program in endothelial cells. In addition to tyrosine phosphorylation, DEP-1 is constitutively phosphorylated on a threonine residue (T1318) proximal to Y1320 in its C-terminal tail suggesting it might be involved in the regulation of Y1320. Indeed, we found that DEP-1 T1318 is phosphorylated, potentially by CK2, and regulates the tyrosine phosphorylation of DEP-1 and its ability to bind to and activate Src. Consistent with this, remodelling of endothelial cell junctions and permeability are impaired in endothelial cells expressing the DEP-1 T1318 mutant. Thus, DEP-1 phosphorylation on T1318 displays a regulatory control over DEP-1 tyrosine phosphorylation and subsequently Src activation and endothelial cell functions in response to VEGF. Our results demonstrating that DEP-1 promotes angiogenic cell responses in endothelial cells, prompted us to consider a possible involvement of DEP-1 in cancer cells, where Src activation has been linked to cancer progression. Thus, although, DEP-1 is believed to act as a tumour suppressor in different cancer types, we hypothesized that it might also promote Src-dependent functions such as migration and invasion in cancer cells. Interestingly, we found that DEP-1 is higher expressed in more invasive basal-like breast cancer cells than in luminal-like cell lines. Moreover, DEP-1 is implicated in the regulation of Src activity, Src-mediated cell motility and appropriate localization of proteins mediating cytoskeletal organization in basal-like breast cancer cell lines. To further support these results, analysis of a breast cancer tissue microarray revealed that DEP-1 expression is associated with a tendency towards reduced overall survival. Thus, our results provide first evidence for a tumour-promoting role of DEP-1 in breast cancer. Altogether, the work performed in the context of this thesis revealed that DEP-1 can similarly behave as a promoter of the angiogenic response and of the pro-invasive phenotype in basal-like breast cancer cell lines, most likely due to its ability to activate Src. This suggests for the first time that DEP-1 expression could contribute to tumour progression and the formation of metastases, and as such, represent a potential new target for anti-angiogenic and anti-cancer therapy.

Bien que la Batterie générale de tests d’aptitudes (BGTA) soit l’outil le plus utilisé pour la sélection en formation professionnelle (FP) au Québec, le fait qu’elle date des années 1940 et qu’aucune étude sur une population québécoise en contexte de formation n’existe, vient remettre en question la pertinence d’utiliser ce test psychométrique pour l’admission en formation. La présente recherche a donc pour but de vérifier si la réussite du test d’admission (la BGTA) permet de prédire la réussite d’une personne candidate dans un programme de FP. Il s’agit donc d’évaluer si la validité prédictive de la BGTA est statistiquement suffisante pour appuyer et justifier une décision relative à l’admission en formation. Pour étudier la validité prédictive de la BGTA dans un contexte de formation professionnelle québécoise, les données recueillies par le Centre de formation professionnelle du 24-juin de Sherbrooke en Estrie entre les années scolaires 1994-1995 et 2004-2005 ont été utilisées. Cette collecte de données a été réalisée avec des élèves ayant réussi la passation de la BGTA comme test d’admission et ayant été admis en FP par la suite. Cette recherche démontre que le genre et le lieu de naissance des sujets étudiés ont une influence sur les résultats aux scores d’aptitudes de la BGTA. Les élèves dont leur lieu de naissance est le Canada et les États-Unis obtiennent généralement des scores d’aptitudes plus élevés à la BGTA que les élèves nés hors du Canada et des États-Unis. Les élèves de genre féminin obtiennent généralement des scores d’aptitudes à la BGTA plus élevés que les élèves de genre masculin. Pour l’ensemble des programmes DEP du Centre 24-juin, l’aptitude générale à apprendre est trop fortement corrélée avec l’aptitude verbale pour en mesurer des concepts distincts. En supprimant cette aptitude des analyses de régression logistique, les aptitudes les plus prédictives de la réussite sont : l’aptitude numérique, de perception spatiale, de coordination visuo-motrice et de dextérité manuelle. Cette recherche a permis de déterminer les aptitudes les plus associées à la réussite d’un DEP et le degré de sensibilité de ces aptitudes. À ce jour, aucune recherche n’avait été faite sur l’admission en FP d’une population québécoise et de sa réussite en formation. Le fait d’étudier la validité prédictive de la BGTA permet d’évaluer l’efficacité du processus d’admission en formation utilisé par plusieurs Centres de formation professionnelle (CFP).

O presente trabalho teve como objetivo estimar a variabilidade genética existente entre touros e linhagens da raça Nelore, essas representadas pelos grandes genearcas, no que se refere à qualidade de carcaça e de carne. Os animais utilizados para coleta de dados de carcaça e carne pertenciam ao projeto de melhoramento genético e de avaliação para emissão de CEIP - Certificado Especial de Identificação e Produção, da Agro-Pecuária CFM-Ltda, e tinham idade entre 21 e 28 meses. Foram analisadas as características peso de carcaça quente (PCQ), área de olho de lombo (AOL), espessura de gordura subcutânea (EGS) e marmoreio (MAR). A qualidade de carne foi avaliada para os períodos de 7, 14 e 21 dias de maturação, quanto às perdas por exsudação (PE), perdas por cozimento (PC) e maciez (MAC). A avaliação da variabilidade genética entre linhagens foi efetuada com base em valores das diferenças esperadas na progênie (DEP) para as características PCQ, AOL, EGS, MAR e MAC aos 7, 14 e 21 dias de maturação. Foi encontrada variabilidade entre os touros e as linhagens estudadas sugerindo que um progresso genético pode ser conseguido pela seleção de animais para características de carcaça e carne dentro da raça Nelore. / The present study had as objective to estimate the genetic variability between steers and breed lines of Nellore, these represented by the greatest breeders, referred to carcass and beef quality. The animals used to collect the samples of carcass and beef belonged to the project of genetic improvement and evaluation to emission of CEIP-Special Certificate of Identification and Production of CFM Farm-Ltda. The animals had age between 21 and 28 months. Were analyzed the characteristics of hot carcass weight (PCQ), rib eye area (AOL), backfat thickness (EGS), marbling (MAR).The beef quality was evaluated for the periods of 7, 14 and 21 days of ageing, as reference the drip loss (PE), cooking loss (PC) and tenderness (MAC). The evaluation of the genetic variability between the breed lines was done based in the values of the expected progeny differences (DEP) of the characteristics of PCQ, AOL, EGS, MAR and MAC at days 7, 14 and 21 of ageing. There was found a variability between steers and the breed lines studied, suggesting that a genetic process may be possible by selecting the animals to carcass and beef characteristics in the Nellore breed.

Submitted by Automa??o e Estat?stica (sst@bczm.ufrn.br) on 2017-08-01T13:23:42Z No. of bitstreams: 1 MyrliAndradeMoreira_DISSERT.pdf: 29310278 bytes, checksum: 061d0be3b2ad8c30a9a4d3962e4582bf (MD5) / Approved for entry into archive by Arlan Eloi Leite Silva (eloihistoriador@yahoo.com.br) on 2017-08-04T20:16:15Z (GMT) No. of bitstreams: 1 MyrliAndradeMoreira_DISSERT.pdf: 29310278 bytes, checksum: 061d0be3b2ad8c30a9a4d3962e4582bf (MD5) / Made available in DSpace on 2017-08-04T20:16:15Z (GMT). No. of bitstreams: 1 MyrliAndradeMoreira_DISSERT.pdf: 29310278 bytes, checksum: 061d0be3b2ad8c30a9a4d3962e4582bf (MD5) Previous issue date: 2016-05-06 / Conselho Nacional de Desenvolvimento Cient?fico e Tecnol?gico (CNPq) / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior (CAPES) / O mapeamento das fei??es em subsuperf?cie pode ser estabelecido em detalhes pela s?smica, utilizando perfilador de subfundo, equipamento hidroac?stico de alta resolu??o. A ?rea de estudo est? situada no rio A?u, delimitada pelo seu estu?rio, litoral setentrional do estado do Rio Grande do Norte, nordeste do Brasil. Localmente, o estu?rio est? inserido em um ambiente constitu?do por: plan?cie de inunda??o fl?vio-marinha, ecossistema de manguezal, bancos arenosos, campos de dunas, pontais e praias arenosas. O presente trabalho teve como objetivo geral a caracteriza??o de fei??es deposicionais e erosionais no estu?rio do Rio A?u, atrav?s da aquisi??o, processamento e interpreta??o de dados s?smicos de alta resolu??o e sondagens geol?gicas. Utilizando o perfilador de subfundo X-Star, do tipo chirp, com faixa de frequ?ncia entre 0,5-7,2 KHz, foram adquiridas 7 linhas s?smicas (quatro transversais e tr?s paralelas ao curso do rio), totalizando, aproximadamente, 16 Km de aquisi??o. As sondagens foram realizadas em 7 pontos distintos ao longo do estu?rio, utilizando dois m?todos de perfura??o: vibracore e percussivo. Os testemunhos apresentaram comprimento variando entre 0,42 m e 4,27 m. Os dados s?smicos processados apresentaram excelente qualidade e permitiram a visualiza??o de diversos elementos arquiteturais caracter?sticos de dep?sitos fluviais, tais como: dep?sitos de acre??o lateral, canal com base erosional c?ncava, dep?sitos de preenchimento. Al?m disso, tamb?m foram observadas formas de fundo do tipo dunas subaquosas e fundo plano. Adicionalmente, refletores bem marcados foram interpretados como: (1) superf?cie de truncamento erosional; e (2) poss?vel contato Pleistoceno-Holoceno. Os testemunhos recuperados nas sondagens apresentaram uma altern?ncia entre n?veis argilosos e n?veis arenosos (variando entre muito fina a grossa) que permitiram a correla??o entre a geof?sica e a geologia da ?rea de estudo. / The mapping of features in the subsurface can be established in detail by the seismic using sub-bottom profiler, high resolution hydroacoustic equipment. The study area is located in the A?u river, bounded by its estuary, northern coast of the Rio Grande do Norte state, NE Brazil. Locally, the estuary is inserted in a coastal environment consisting of: fluvio-marine floodplain, mangrove ecosystem, sandy banks, dune fields, spits and sandy beaches. This study aimed to characterize the depositional and erosional features from A?u River estuary, through the acquisition, processing and interpretation of high-resolution seismic data and cores. Using the X-Star sub-bottom profiler (chirp), with frequency range between 0.5 to 7.2 kHz, were acquired seven seismic profiles (four horizontal and three parallel to the river course), totalizing approximately 16 km of seismic acquisition. The cores were done in seven different points along the estuary, using two drilling methods: vibracore and percussive. The length of the cores varied between 0.42 m and 4.27 m. Processed seismic data showed excellent quality and allowed the visualization of several architectural elements characteristic of estuarine deposits, such as: lateral accretion deposits, channel concave erosional base, infill deposits. Moreover, subaqueous dunes and flat bottom bedforms were also observed. Additionally, well market reflectors were interpreted as: (1) erosional truncation surface; and (2) possible Pleistocene-Holocene contact. The cores showed an intercalation between clayey and sandy layers (ranging from very fine to course) which allowed the correlation between geophysics and geology on the study area.

O presente trabalho teve como objetivo estimar a variabilidade genética existente entre touros e linhagens da raça Nelore, essas representadas pelos grandes genearcas, no que se refere à qualidade de carcaça e de carne. Os animais utilizados para coleta de dados de carcaça e carne pertenciam ao projeto de melhoramento genético e de avaliação para emissão de CEIP - Certificado Especial de Identificação e Produção, da Agro-Pecuária CFM-Ltda, e tinham idade entre 21 e 28 meses. Foram analisadas as características peso de carcaça quente (PCQ), área de olho de lombo (AOL), espessura de gordura subcutânea (EGS) e marmoreio (MAR). A qualidade de carne foi avaliada para os períodos de 7, 14 e 21 dias de maturação, quanto às perdas por exsudação (PE), perdas por cozimento (PC) e maciez (MAC). A avaliação da variabilidade genética entre linhagens foi efetuada com base em valores das diferenças esperadas na progênie (DEP) para as características PCQ, AOL, EGS, MAR e MAC aos 7, 14 e 21 dias de maturação. Foi encontrada variabilidade entre os touros e as linhagens estudadas sugerindo que um progresso genético pode ser conseguido pela seleção de animais para características de carcaça e carne dentro da raça Nelore. / The present study had as objective to estimate the genetic variability between steers and breed lines of Nellore, these represented by the greatest breeders, referred to carcass and beef quality. The animals used to collect the samples of carcass and beef belonged to the project of genetic improvement and evaluation to emission of CEIP-Special Certificate of Identification and Production of CFM Farm-Ltda. The animals had age between 21 and 28 months. Were analyzed the characteristics of hot carcass weight (PCQ), rib eye area (AOL), backfat thickness (EGS), marbling (MAR).The beef quality was evaluated for the periods of 7, 14 and 21 days of ageing, as reference the drip loss (PE), cooking loss (PC) and tenderness (MAC). The evaluation of the genetic variability between the breed lines was done based in the values of the expected progeny differences (DEP) of the characteristics of PCQ, AOL, EGS, MAR and MAC at days 7, 14 and 21 of ageing. There was found a variability between steers and the breed lines studied, suggesting that a genetic process may be possible by selecting the animals to carcass and beef characteristics in the Nellore breed.

Le cancer épithélial de l’ovaire (CÉO) est le cancer gynécologique le plus létal. Bien que certains progrès aient été accomplis, une meilleure compréhension des mécanismes moléculaires impliqués dans le développement de ce cancer est requise. Notre laboratoire a démontré que la protéine tyrosine phosphatase DEP-1 était impliquée dans l’activation de Src, la survie, la migration et l’invasion des cellules endothéliales en réponse au VEGF. Des études ont proposé que Src ait également un rôle important dans la progression tumorale du CÉO. Ainsi, nous nous intéressons au rôle de DEP-1 dans le potentiel invasif du CÉO. Nous avons observé des niveaux d’expression variables de DEP-1 dans 6 lignées cellulaires du CÉO et constaté que ceux-ci corrèlent positivement avec le potentiel invasif des cellules dans le Matrigel. Des expériences d’ARNi ont démontré que la réduction de l’expression de DEP-1 inhibe des voies de signalisation pro-invasives telles que la phosphorylation de Src et de Cortactine, ainsi que la localisation de Cortactine aux lamellipodes. Cette déplétion de DEP-1 a également eu pour effet de diminuer d’autres voies de signalisation pro-tumorales, tel que la phosphorylation de l’EGFR et de P65 (NfκB). Conséquemment, la déplétion de DEP-1 par transfection d’ARNi se traduit par une perte du potentiel invasif des cellules, et une diminution de la résistance des cellules au Carboplatin. L’analyse de l’expression de DEP-1 par immunohistochimie dans les tumeurs ovariennes révèle l’existence d’une corrélation positive entre l’expression en protéine de DEP-1 et le cancer de l’ovaire de grade élevé et la survie des patientes, qui a également été confirmé sur une puce à ARN. Nos résultats suggèrent que DEP-1 favoriserait la progression tumorale du cancer épithélial de l’ovaire. Nous avons démontré que DEP-1 est impliquée dans l’invasion in vitro, et que son expression est associée à un cancer de l’ovaire plus agressif, faisant ainsi de DEP-1 une cible thérapeutique potentiellement intéressante. / Epithelial ovarian cancer (EOC) is the most lethal gynecological cancer. Our laboratory has previously shown that the protein tyrosine phosphatase DEP-1 is involved in Src activation, survival, migration and invasion of endothelial cells in response to VEGF. Studies have shown that Src may be implicated in the progression of epithelial ovarian cancer progression. Thus, we were interested in determining if DEP-1 had a role in the promotion of the Src invasive pathway in EOC. First, we have observed a variable protein expression of DEP-1 in six EOC cell lines, and that there was a positive correlation with invasion in Matrigel. We also showed in RNAi experiments that inhibition of DEP-1expression resulted in the decreased phosphorylation of Src and Cortactin, also loss of Cortactin localisation at the cellular membrane. We also observed dysregulation of other pro-tumoral pathways like EGFR and P65 (NfκB) diminution of phosphorylation. Consequently, DEP-1 depletion resulted in loss of invasive capacities of most of the cell lines, and diminution of chemoresistance in response to Carboplatin. Analysis of DEP-1 in EOC tumors revealed the existence of a positive correlation with an aggressive form of ovarian cancer, high grade status, and poorer survival. These results suggest a positive role of DEP-1 in tumor progression of EOC. Our results show for the first time that DEP-1 is implicated in invasion in vitro, and is associated with the most aggressive form of EOC. Thus, DEP-1 is an interesting therapeutical target for EOC.

A MUC1 (MUC1) e a osteopontina (SPP1) são glicoproteínas expressas na superfície luminal uterina com funções na proteção e adesão celular. A MUC1 possui função antiadesiva, enquanto a osteopontina desempenha função adesiva. A expressão de ambas é regulada pelo hormônio esteróide progesterona. Durante a fase receptiva do útero, a MUC1 é inibida por este hormônio, enquanto a osteopontina é estimulada. O objetivo deste trabalho é caracterizar o polimorfismo genético destas moléculas e analisar a associação entre o polimorfismo, o diagnóstico de gestação e as diferenças esperadas na progênie (DEP) de várias características em novilhas da raça Nelore (Bos taurus indicus). A amostra foi constituída por 309 novilhas procedentes de duas fazendas participantes do Programa de Melhoramento Genético da Raça Nelore (PMGRN). A amostra da primeira fazenda incluiu 56 novilhas prenhas e foi utilizada para caracterização do polimorfismo e da estrutura do número variável de repetições em tandem (VNTR) MUC1 na raça Nelore. A segunda amostra foi constituída por 76 novilhas com resultado positivo de gestação e 156 com resultado negativo de gestação e foi utilizada para caracterização do polimorfismo dos genes MUC1 e SPP1 na raça Nelore, assim como para análise da associação entre os polimorfismos e os fenótipos. O gene MUC1 apresentou 5 alelos constituídos por um VNTR formado por uma seqüência de 60 nucleotídeos. A seqüência da repetição consensus foi idêntica às seqüências descritas em caprinos e em Bos taurus taurus. Descrevemos a seqüência de uma terceira repetição consensu na raça Nelore. O alelo 1 apresentou 10 repetições, o alelo 2 apresentou 12 repetições, o alelo 3 apresentou 15 repetições, o alelo 4 foi formado por 18 repetições, e o alelo 5 apresentou 24 repetições. O alelo com menor número de repetições apresentou a maior freqüência, sendo 0,70 na amostra do 1º grupo e 0,80 na amostra do 2º grupo. Os alelos 2, e 3 tiveram a segunda e terceira maior freqüência, sendo seguidos pelos alelos 4 e 5. A análise estatística não evidenciou associação entre o polimorfismo do gene MUC1 e o diagnóstico de gestação e entre o polimorfismo e os valores das diferenças esperadas na progênie das características consideradas economicamente importantes. Na amostra referente às novilhas da segunda fazenda, não identificamos o polimorfismo de nucleotídeo simples no íntron 4 (T/C) do gene SPP1 da osteopontina, como descrito na raça Holandesa. Sugerimos que a ausência deste polimorfismo possa constituir uma característica específica em Bos taurus indicus. Porém, dada a associação já descrita entre polimorfismo do gene SPP1 e características de crescimento, não descartamos a hipótese de que, assim como o MUC1, tenha ocorrido uma seleção indireta devido aos critérios aplicados pelo Programa de Melhoramento Genético da Raça Nelore. / MUC1 (MUC1) and osteopontin (SPP1) are glycoproteins expressed in the uterine luminal surface with predict functions in protection and cell adhesion. MUC1 has anti-adhesive role and osteopontin has adhesive role. The expression of both molecules is regulated by the steroid hormone, progesterone. During the receptive period for embryo implantation in the uterus, MUC1 is inhibited by progesterone and the osteopontin is stimulated. The objective of this work is to characterize the genetic polymorphism of these molecules, and to characterize associations between the polymorphisms, gestation rate and the expected progeny difference (EPD) in the Nelore breed (Bos taurus indicus). The study group comprised 309 heifers derived from two participating farms of the Nelore Cattle Breeding Program (PMGRN). The first farm provided 56 fertile female for the study for the characterization of the MUC1 polymorphism and the variable number of tandem repeats (VNTR) genomic structure in the Nelore breed. The second farm contributed 76 heifers with confirmed gestation and 156 no-pregnant female that were used to characterize both gene polymorphisms and to analyze the association between the MUC1 and SPP1 polymorphisms and the phenotypes. The MUC1 gene presented five alleles caused by length differences generated by a VNTR of 60 nucleotides. The consensus repeat sequence was identical to the caprine and Bos taurus taurus sequence. In this study we described the sequence of the third consensus repeat in the Nelore breed. Allele 1 presented with 10 repeats, allele 2 presented with 12 repeats, allele 3 presented with 15 repeats, allele 4 had 18 repeats and allele 5 had 24 repeats. Allele 1 had the smallest size and was the most frequent (0.70) in the group 1 and 0.80 in the group 2. Alleles 2 and 3 were the next most frequent followed by alleles 4 and 5. The ?2 test showed that the polymorphism was not significantly associated with the diagnostic of gestation and the EPD values. In this Nelore study group it was not possible to identify the single nucleotide polymorphism (T/C) of the SPP1 gene previously described in Holstein breed. The absence of this polymorphism could be specific to the Nelore cattle. However, considering the correlation between the SPP1 polymorphism and growth parameters, an indirect selection could happen due to the established criteria within the Nelore Cattle Breeding Program.

Made available in DSpace on 2015-04-14T14:33:26Z (GMT). No. of bitstreams: 1 410179.pdf: 210259 bytes, checksum: abefc6f51a0779f19c500084382eba19 (MD5) Previous issue date: 2008-08-04 / A proposta deste trabalho ? demonstrar a subsist?ncia de fundamento jur?dico para decreta??o da pris?o civil do devedor de alimentos e do deposit?rio infiel (no caso de dep?sito t?pico e na hip?tese de dep?sito judicial), mesmo ap?s a ratifica??o pelo Brasil de dois dos mais importantes tratados internacionais de prote??o dos direitos humanos, quais sejam, o Pacto Internacional dos Direitos Civis e Pol?ticos e a Conven??o Americana sobre Direitos Humanos (tamb?m chamada de Pacto de San Jos? da Costa Rica). Trar-se-? ? discuss?o, inicialmente, o alcance da express?o d?vida, prevista na norma do art. 5?, LXVII, da Constitui??o Federal, para estabelecer o conceito de pris?o civil e sua natureza jur?dica. As origens hist?ricas do instituto tamb?m ser?o revisitadas, merecendo aten??o, no particular, o tratamento conferido ? pris?o civil pelos diversos textos constitucionais brasileiros, a partir da Constitui??o Federal de 1824. Tamb?m ser? objeto de an?lise a rela??o existente entre a pris?o civil e os Pactos Internacionais sobre direitos Humanos, quando, ent?o, o foco estar? centrado na forma como as normas enunciadas nesses tratados se incorporam ao direito interno e qual o status que lhes ? conferido. Defender-se-? a id?ia de que os tratados ou conven??es internacionais, uma vez regularmente incorporados ao direito interno, e sem que se sujeitem ao processo legislativo das emendas constitucionais (art. 5?, ? 3?, da CF), situam-se, no sistema jur?dico brasileiro, nos mesmos planos de validade, efic?cia e de autoridade em que se posicionam as leis ordin?rias. Na seq??ncia, fixar-se-? o exato alcance da norma do art. 5?, ? 2?, CF, a qual estabelece que os Direitos e garantias expressos nesta Constitui??o n?o excluem outros decorrentes do regime e dos princ?pios por ela adotados, ou dos tratados internacionais em que a Rep?blica Federativa do Brasil seja parte. Procurar-se-? demonstrar, a partir da interpreta??o dessa norma, que a tese da equipara??o entre os direitos fundamentais decorrentes dos tratados internacionais e aqueles direitos com sede na Constitui??o formal, por for?a do art. 5?, ? 2?, da CF, n?o se harmoniza com o novo ? 3?, introduzido no aludido art. 5?. Sendo assim, ? constitucional, segundo a tese aqui defendida, a pris?o civil nos casos de dep?sito genu?no (o dep?sito cl?ssico previsto no CC) e, tamb?m, na hip?tese de inadimplemento volunt?rio e inescus?vel de d?bito alimentar. Para chegar-se a tais conclus?es, ser?o diferenciadas, primeiramente, as diversas esp?cies de dep?sito, com vista a estabelecer um conceito para a express?o deposit?rio infiel, contemplada no texto constitucional. Depois, diante da possibilidade da pris?o para o inadimplente de d?bito alimentar, defendida neste trabalho, o estudo voltar-se-? para as v?rias classes de alimentos e os meios coercitivos previstos na legisla??o constitucional e infraconstitucional para constrang?-lo ao cumprimento de sua obriga??o. Seguindo no exame do tema, a preocupa??o direcionar-se-? a evidenciar que o deposit?rio judicial (que assume um munus p?blico, como auxiliar da justi?a), ao descumprir o compromisso assumido perante a autoridade judicial, relativo ? restitui??o da coisa depositada, estar? sujeito ? pris?o, a qual poder? ser decretada nos pr?prios autos da execu??o, sem que tal medida represente qualquer afronta ?s normas inseridas nos tratados internacionais ratificados pelo Brasil, ou mesmo viola??o ao princ?pio do due process of law. Por fim, o procedimento para imposi??o da pris?o civil, nos dois casos em que se admite a sua constitucionalidade, n?o ficar? ? margem desta exposi??o, merecendo especial destaque as quest?es de natureza processual mais controvertidas, quer na doutrina, quer na jurisprud?ncia, tais como a apresenta??o da resposta, contradit?rio, a ampla defesa, a resolu??o do incidente que decreta a pris?o, os recursos cab?veis, os efeitos da decis?o, o prazo da pris?o e o seu regime de cumprimento.

This research used Geographical Information System (GIS) data to estimate the acreage of wetland loss due to small-scale activities (taking into account exempt, permitted, and unauthorized activities) in the Southwest District of the Department of Environmental Protection (DEP) between 2006 and 2011 and compared that net loss with the unmitigated wetland net loss that DEP documented during that time for authorized activities and violations that were discovered. The comparison allowed an estimation of the extent of undocumented small-scale unmitigated wetland loss that occurred during those six years. DEP records show that 88% of non-compliance cases remain unresolved, and the net loss of wetlands that was documented by DEP is 28.66 acres. The change in acreage of DEP-regulated wetlands (and wetlands on agricultural parcels) as determined by GIS analysis is 1,250 acres gained. However, evidence shows that some of the water features categorized as wetlands in the GIS interface are reservoirs which may not be providing the functions necessary to mitigate for wetland loss. Evidence also shows that many small-scale wetland alterations were not detected by remote sensing, indicating that there is a great level of uncertainty in the GIS interpretation. Consequently, achievement of the No Net Loss goal in Florida cannot be determined using documented alterations, nor can it be determined by use of medium-high resolution aerial imagery. The analysis can be extrapolated to the rest of Florida, where State wetland protection regulations are constant.