Une analyse génomique (Comparative Genomic Hybridization) a été réalisée sur une cohorte d'adénomes et de tumeurs coliques et a mis en évidence, parmi d'autres altérations, la délétion de la région 1p36.12 dans 23% des adénomes et 47% des carcinomes. Parmi les 15 gènes ayant une fonction connue retrouvés dans cette zone, le gène codant pour le facteur de transcription E2F2 a été retenu en raison de son implication dans des processus cellulaires clés. Une analyse de Kaplan- Meier a montré que la délétion de E2F2 est un facteur de bon pronostic de survie sans progression. Afin de mieux cerner l'implication des gènes ciblés par la micro-délétion en 1p36.12, une étude fonctionnelle in vitro et in vivo de la perte de fonction de E2F2 a été réalisée, et étendue à celle de ID3 dont le gène est le voisin direct de E2F2. Nos observations indiquent qu'in vivo, la perte d'E2F2 favorise la croissance tumorale et bloque le développement de métastases. Dans le cadre d'une collaboration avec l'équipe de biochimiste du Pr Céline TARNUS (U.H.A.), une étude pilote a été réalisée pour prouver l'efficacité anti-tumorale de nouveaux inhibiteurs hautement sélectifs pour l'aminopeptidase N.

Le succès des espèces invasives dépend de l'adéquation entre leurs traits d'histoire de vie et les caractéristiques environnementales (biotiques et abiotiques) de leurs nouveaux habitats. Le succès invasif d'une espèce peut donc reposer sur sa pré-adaptation, être déclenché par la levée de certaines pressions sélectives, les perturbations, ou encore la réponse rapide de l'organisme aux nouvelles contraintes sélectives. La plasticité phénotypique et les processus évolutifs sont ainsi des paramètres essentiels dans les invasions biologiques, en faisant des situations privilégiées pour observer les processus écologiques et évolutifs en temps réel. Nous nous sommes intéressés aux réponses morphologiques et écophysiologiques exprimées dans le temps et l'espace au cours de l'invasion des Îles Kerguelen (archipel subantarctique) par le carabique prédateur Merizodus soledadinus et la mouche saprophage Calliphora vicina, dont les stratégies de vie sont contrastées. Nous montrons la différenciation morphométrique de populations de M. soledadinus en fonction de leur temps de résidence, ainsi que les changements rapides de la morphologie de l'aile de C. vicina dans ces îles où l'inaptitude au vol est la règle. Une attention particulière est accordée au rôle de la plasticité phénotypique de M. soledadinus dans la colonisation de nouveaux habitats (plasticité physiologique à la salinité) et dans son maintien durable malgré l'impact qu'il exerce sur la disponibilité des proies (plasticité trophique). Ces ajustements à plus ou moins long terme sont des éléments déterminants du succès invasif de ces deux insectes à mesure qu'ils progressent et rencontrent de nouveaux régimes de sélection.

Invasive exotic species threaten the biodiversity and function of native ecosystems. Existing models, attempting to predict and control successful invaders, often emphasize isolated stages of in their life history and fail to formalize interactions between exotic species and recipient environments. In order to elucidate key mechanisms in the success of select invaders, I investigated the role of dispersal, establishment, proliferation, and persistence in their threat to natural areas. Focusing on Riding Mountain National Park, Manitoba, Canada, I integrated the native climatic range and biological traits of 251 exotic vascular plants reported inside and outside the park. Based on their climatic range in Europe, 155 among 174 exotic plant species absent from the Park were predicted to establish within its boundaries; among these, 40 clonal perennials were considered the highest threat to the Park’s biodiversity. Focusing on smooth brome (Bromus inermis Leyss.), a Eurasian perennial, threatening the structure and function of native prairies throughout the Great Plains, I extended my research to investigate the role of dispersal, establishment, proliferation, and persistence in characterizing its threat to the endemic diversity of northern fescue prairies, protected within Riding Mountain National Park. Patterns of smooth brome invasions were contingent on the type of propagules dispersed. The shallow dispersal gradient of individual florets combined with the steeper gradient of panicles and spikelets suggested that smooth brome is capable of simultaneously invading along dense fronts as well as by establishing isolated foci. While low correlations between the number of dispersed seeds and their recruitment suggested post-dispersal transport, seedling establishment remained contingent on prairie diversity. Seedling biomass increased with declining plant diversity, however, its impact depended on the availability of soil nitrogen. As a result, disturbed areas, preserving the root function of native plants, resisted smooth brome establishment. Even though low nitrogen contributed to a decline in seedling biomass, physiological integration between ramets facilitated their vegetative proliferation in low resource environments. Despite its rapid establishment and proliferation, smooth brome productivity declined at the center of invading clones. Although field and greenhouse observations failed to implicate soilborne pathogens, reasons for the observed decline remain unresolved. My research demonstrates that while Riding Mountain National Park and other natural areas in western Canada will continue to be impacted by exotic plants, integrating key stages in their life history provides an important conceptual framework in predicting their threat to natural areas and prioritizing management.

Micro (mi)RNAs have recently been found to play an important role in cancer biology. In order to further understand how miRNAs affect prostate tumour progression, we evaluated miRNA expression in two invasive prostate tumour lines, PC3 and DU145. We then focused our evaluation on a novel miRNA, miR-105, whose levels were significantly decreased in both tumour cell lines as compared to normal prostate epithelial cells. As miR-105 levels were reduced in prostate tumour cell lines, we restored its expression following transfection of cells with mimic constructs to over-express miR-105 in both cell lines, in order to determine its effect on various tumourigenic properties. Over-expression caused decreased tumour cell proliferation, anchorage-independent growth and invasion in vitro and inhibited tumour growth in vivo. We further identified CDK6 as a putative target of miR-105, which likely contributed to its inhibition of tumour cell growth. Our results suggest that miR-105 inhibits tumour cell proliferation and may be an interesting target to regulate tumour growth or potentially used as a biomarker to differentiate between less and more aggressive tumours in patients.

First appearing on potsherds around 3300 BC, the Indus script was primarily in use during the Mature Harappan period (ca. 2600-1900 BC) in the Indus Valley region, centred in the north-western region of the Indian Subcontinent. It is one of the last remaining undeciphered scripts of the ancient world. A great number of Indus inscriptions, however, have been uncovered at many archaeological sites in the Persian Gulf, discoveries that corroborate the inclusion of the Indus civilization as an active participant in the Mesopotamian-dominated Gulf trade of the 3rd millennium. In addition to exploring the current state of research surrounding the Indus decipherment attempts, the thesis will examine new perspectives on ancient history, arguing in favour of various possibilities of Mesopotamian, Elamite, and/or pre-dynastic Egyptian (North East African) cultural presences or influences in the ancient Indus River basin.

This thesis describes how life history characteristics of the varnish clam (Nuttallia obscurata), and interactions with the physical environment and other species, have contributed to its successful invasion in coastal British Columbia. Lab and field experiments were conducted to investigate varnish clam larval ecology (i.e. larval rearing experiments), adult population dynamics (i.e. annual population surveys, mark-recapture and length-frequency analysis, growth modeling) and ecological interactions with native species (i.e. predator/prey preference feeding trials). Using these results, a matrix demographic model was developed to determine which life history stage contributes the most to varnish clam population growth. Larval rearing experiments indicated that temperature and salinity tolerances of varnish clam larvae are comparable to native species, however the planktonic phase is slightly longer (3-8 weeks). Based on local oceanographic circulation, varnish clam larvae have the potential to disperse throughout their entire geographic range in just one reproductive season. Varnish clam population surveys revealed spatiotemporal variation in density and size. No relationships were evident between varnish clam density and the number or density of co-occurring bivalve species. Length-frequency analysis suggested that recruitment varies among sites, with high post-settlement mortality coinciding with high recruitment. The presence of similar recruitment pulses at geographically separate sites indicates regional scale processes may influence recruitment. Individual growth rates iii varied among sites, with higher growth corresponding to lower population densities and water temperature. Monthly survival rates ranged from 0.81 – 0.99 and were lower for clams 10-30 mm. Predator/prey preference feeding trials showed that crabs prefer varnish clams to local species when clam burial depth is limited. Crabs therefore have the potential to influence varnish clam distributions, particularly on beaches where the varnish clam is unable to bury deeply. Based on matrix demographic analysis, adult survival (e.g. clams ≥ 40 mm) is the most crucial factor for varnish clam population growth, and drives the observed population growth differences between sites. This study of the varnish clam invasion demonstrates that its success lies in both species (e.g. lengthy planktonic phase, high survival) and regional (e.g. favourable ocean circulation patterns for rapid dispersal) characteristics. Measures to reduce introductions should be targeted in areas where introductions are likely to have the furthest reaching impacts.

The objective of this thesis is to analyze the bilateral relations between the US and Saudi Arabia in the period between 1990 and 2003. In this context, the aim is to find out an answer to the question of how the relations between the US-Saudi Arabia have strained after September 11. Accordingly, the thesis contains four main parts. In the first part of the study, the historical background of US-Saudi relations up to the 1990-1991 Gulf Crisis, which was based on oil for security exchange, is studied. In the second part of the study, the security dilemma of Saudi Arabia, the challenges Saudi Arabia faced during the 1990s, and how these challenges affected its relations with the US are discussed. In the third part, September 11 and how global issues like war on terrorism, war in Iraq and democratization in the Middle East came into the agenda of the relationship is scrutinized. Accordingly, this thesis has reached to the following conclusions: First, after September 11, the relations between the two countries became more problematic and have affected by both global issues as well as domestic debates in both countries. Second, despite increasingly problematic nature of the relationship, the two countries managed to continue their strategic relationship, particularly as regards to &ldquo / war on terrorism&rdquo / .

More than a century ago in their definitive work “The Right to Privacy” Samuel D. Warren and Louis D. Brandeis highlighted the challenges posed to individual privacy by advancing technology. Today’s workplace is characterised by its reliance on computer technology, particularly the use of email and the Internet to perform critical business functions. Increasingly these and other workplace activities are the focus of monitoring by employers. There is little formal regulation of electronic monitoring in Australian or United States workplaces. Without reasonable limits or controls, this has the potential to adversely affect employees’ privacy rights. Australia has a history of legislating to protect privacy rights, whereas the United States has relied on a combination of constitutional guarantees, federal and state statutes, and the common law. This thesis examines a number of existing and proposed statutory and other workplace privacy laws in Australia and the United States. The analysis demonstrates that existing measures fail to adequately regulate monitoring or provide employees with suitable remedies where unjustifiable intrusions occur. The thesis ultimately supports the view that enacting uniform legislation at the national level provides a more effective and comprehensive solution for both employers and employees. Chapter One provides a general introduction and briefly discusses issues relevant to electronic monitoring in the workplace. Chapter Two contains an overview of privacy law as it relates to electronic monitoring in Australian and United States workplaces. In Chapter Three there is an examination of the complaint process and remedies available to a hypothetical employee (Mary) who is concerned about protecting her privacy rights at work. Chapter Four provides an analysis of the major themes emerging from the research, and also discusses the draft national uniform legislation. Chapter Five details the proposed legislation in the form of the Workplace Surveillance and Monitoring Act, and Chapter Six contains the conclusion.

This thesis is a broadly chronological study of representations of Japan and the Japanese in Australian novels, stories and memoirs from the late nineteenth century to the twenty-first century. Adopting Edward Said???s Orientalist notion of the `Other???, it attempts to elaborate patterns in which Australian authors describe and evaluate the Japanese. As well as examining these patterns of representation, this thesis outlines the course of their development and change over the years, how they relate to the context in which they occur, and how they contribute to the formation of wider Australian views on Japan and the Japanese. The thesis considers the role of certain Australian authors in formulating images and ideas of the Japanese ???Other???. These authors, ranging from fiction writers to journalists, scholars and war memoirists, act as observers, interpreters, translators, and sometimes ???traitors??? in their cross-cultural interactions. The thesis includes work from within and outside ???mainstream??? writings, thus expanding the contexts of Australian literary history. The major ???periods??? of Australian literature discussed in this thesis include: the 1880s to World War II; the Pacific War; the post-war period; and the multicultural period (1980s to 2000). While a comprehensive examination of available literature reveals the powerful and continuing influence of the Pacific War, images of ???the stranger???, ???the enemy??? and later ???the ally??? or ???partner??? are shown to vary according to authors, situations and wider international relations. This thesis also examines gender issues, which are often brought into sharp relief in cross-cultural representations. While typical East-West power-relationships are reflected in gender relations, more complex approaches are also taken by some authors. This thesis argues that, while certain patterns recur, such as versions of the ???Cho-Cho-San??? or ???Madame Butterfly??? story, Japan-related works have given some Australian authors, especially women, opportunities to reveal more ???liberated??? viewpoints than seemed possible in their own cultural context. As the first extensive study of Japan in Australian literary consciousness, this thesis brings to the surface many neglected texts. It shows a pattern of changing interests and interactions between two nations whose economic interactions have usually been explored more deeply than their literary and cultural relations.

Neospora caninum (filo Apicomplexa) é um parasita obrigatório intracelular como todos os membros deste filo, alguns reconhecidos por causarem doenças com impacto relevante na saúde humana (Plasmodium e Toxoplasma) e veterinária (Babesia, Eimeria e Cryptosporidium). Causador da neosporose, N. caninum vem emergindo como um dos maiores causadores de abortos infecciosos em bovinos, levando a consideráveis perdas econômicas na bovinocultura mundial. Devido à sua recente descoberta, o conhecimento sobre diversos processos bioquímicos de N.caninum ainda é limitado, demandando novas pesquisas para a compreensão de seus mecanismos de sobrevivência e consequente identificação de alvos para intervenção terapêutica. O processo de invasão celular é bastante investigado em pesquisas envolvendo apicomplexas, uma vez que a sobrevivência desses parasitas depende do sucesso de sua entrada na célula hospedeira. Proteínas secretadas de organelas filo-específicas (micronemas, roptrias e grânulos densos) estão intimamente envolvidas com a invasão celular. Elas são responsáveis pela interação inicial com a célula hospedeira, participam da junção de movimento formada no momento da invasão, e contribuem para a estabilização do vacúolo parasitóforo. Neste trabalho as proteínas secretadas por taquizoítas de N. caninum foram investigadas de duas formas: (1) por caracterização molecular de proteínas com domínio Apple; e (2) por estudo do secretoma do parasita. Os domínios proteicos do tipo Apple são caracterizados pela capacidade de interação proteína-proteína e proteína-carboidrato, e estão presentes em algumas proteínas micronêmicas com propriedades adesivas. Neste trabalho três proteínas de N. caninum contendo domínios Apple foram caracterizadas: MIC17A, MIC17B e MIC17C. A análise das sequências proteicas e das estruturas dos domínios Apple, obtidas por modelagem molecular, mostraram alta identidade sequencial e estrutural entre MIC17A e MIC17C. Apesar de ser paráloga às outras duas, MIC17B apresenta diferenças importantes em sua sequência e estrutura. Para MIC17B e MIC17C foram realizados experimentos de detecção das proteínas nativas nos extratos total e secretado do taquizoíta que sugerem diferentes formas de processamento entre essas proteínas no parasita. Para MIC17B foi confirmada a localização em micronemas, num padrão diferente do observado para MIC17C. Os ensaios de invasão combinados aos de localização indicam que estas proteínas estejam relacionadas ao processo de invasão celular, porém, suas funções permanecem desconhecidas. O secretoma é o conjunto de proteínas secretadas pelo parasita e, para explorar a composição deste extrato (ESA) no taquizoíta de N. caninum, duas abordagens complementares foram utilizadas. Na primeira abordagem foram identificadas as proteínas presentes no ESA por espectrometria de massas. Na segunda abordagem realizou-se uma ii quantificação relativa das proteínas, marcadas por dois isótopos, nos extratos totais de taquizoítas submetidos ou não ao estímulo secretório. O resultado esperado seria com as proteínas secretadas diminuídas no parasita estimulado. Em ambas as abordagens foram utilizadas técnicas de espectrometria de massas de alta resolução (nanoLC-MS/MS), o que resultou num alto número de identificações; 615 proteínas no ESA e 2011 proteínas quantificadas. A comparação das duas abordagens permitiu o reconhecimento de proteínas com maior probabilidade de secreção. Uma rede de interação entre as proteínas diferencialmente expressas foi predita, gerando resultados que, associados às informações sobre as proteínas aumentadas, permitiram uma investigação sobre proteínas potencialmente envolvidas com a regulação do metabolismo relacionado à secreção. Os resultados obtidos por ambos os estudos aqui demonstrados somam conhecimento acerca do parasita N. caninum e demonstram ser úteis para guiar a busca e seleção de alvos a serem investigados para o desenvolvimento de terapêutica contra a neosporose. / Neospora caninum (Apicomplexa phylum) is an obligatory intracellular parasite like all members from this phylum, some causing diseases with relevant impact on human (Plasmodium and Toxoplasma) and veterinary (Babesia, Eimeria and Cryptosporidium) health. Causative agent of neosporosis, N. caninum has emerged as one of the leading causes of infectious abortion in cattle, generating huge economical losses in worldwide livestock. Due to its recent discovery, knowledge of N. caninum biochemical processes remains scarce, demanding new research for comprehending its survival mechanisms and, consequently, identifying new targets for therapeutic intervention. The invasion process has often been investigated in apicomplexans since their survival depends on the success of their entry into the host cell. Proteins secreted from phylum-specific organelles (micronemes, rhoptries and dense granules) are deeply involved with invasion. They are responsible for the initial interaction with the host cell; participate of the moving junction formed in the moment of invasion; and contribute for the stabilization of the parasitophorus vacuole. In this study, the proteins secreted by N. caninum tachyzoites were investigated in two ways: (1) the molecular characterization of Apple domaincontaining proteins; and (2) exploring the parasite secretome. The Apple protein domains are characterized by the ability to interact as protein-protein and proteincarbohydrate, and are present in some microneme proteins with adhesive properties. Here three N. caninum proteins containing Apple domains were characterized: MIC17A, MIC17B and MIC17C. Analyses of the Apple domains sequences and structures, obtained by molecular modeling, revealed high sequential and structural identities between MIC17A and MIC17C. Although being a paralog of the other two proteins, MIC17B presents significant differences in its sequence and structure. Experiments were performed for native MIC17B and MIC17C detection in the total and secreted tachyzoite extracts, suggesting different processing forms for these proteins in the parasite. For MIC17B, the microneme localization was confirmed, differently from the pattern observed for MIC17C. Invasion and localization assays indicated that these proteins are related to the cell invasion process; nevertheless, their functions remain unknown. The secretome is the set of proteins secreted by the parasite and, to explore this extract (ESA) composition in N. caninum, two complementary approaches were used. Firstly proteins present in ESA were identified by mass spectrometry. In the second approach, a relative quantification was performed on the proteomes of ethanol stimulated/non stimulated tachyzoites, expecting that the secreted proteins would be down regulated at the stimulated parasite. Both approaches were performed with high resolution mass spectrometry techniques (nanoLC-MS/MS), reaching a high number of identifications: 615 proteins iv in ESA and 2011 quantified proteins. The comparison between both approaches allowed the recognition of the most likely secreted proteins. An interaction network was predicted, involving the differentially expressed proteins. These results, associated with the information of up regulated proteins, allowed the investigation of proteins potentially involved with the secretion metabolism regulation. The findings from our two studies add up knowledge about N. caninum and demonstrate to be useful in guiding the search and selection for new targets for therapeutic development against neosporosis.