Tato diplomová práce je rozdělena na teoretickou a praktickou část a zabývá se výskytem polovětných konstrukcí tvořených některým z neosobních slovesných tvarů ve španělském jazyce a volbou jejich ekvivalentů při překladu do češtiny. Cílem této práce je poskytnout přehled vlastností, zvláštností a dalších poznatků o polovětných konstrukcích ze španělsky a česky psaných zdrojů. Široké spektrum gramatik, publikací a skript, včetně dvoujazyčného elektronického korpusu literárních děl, přináší nejen velké množství informací o těchto konstrukcích, ale také rozbor volených jazykových prostředků při překladu z jednoho jazyka do druhého a vyhodnocení získaných údajů.

This dissertation is a challenge to the Pentecostal churches, particularly, the Apostolic Faith Mission Church in Tumahole, to take an action in meeting the challenges posed by HIV/AIDS. This disease, HIV/AIDS, is the latest enemy to human life that the nations are faced with. In the newspapers like Sowetan, there is an article almost daily about HIV and AIDS. In this dissertation, I have tried to show shocking figures of how this disease is spreading in Africa. The seriousness of the disease, unlike other diseases, is its in curability. The secular organisations are far ahead of the churches in as far as the relevant programmes on combating HIV/AIDS are concerned. Despite these massive programmes, the disease is spreading like the wild fire. Deducing from this background, it is no longer the question of whether the Pentecostal churches have any role to play, but what specific role should the church play in this challenge. In this challenging times, many people look at the church as one of the most important institute that would play a positive role in bringing hope to the hopeless. / Christian Spirituality, Church History and Missiology / M. Th. (Missiology (Urban Ministry))

This diploma thesis examines changes, which the Czech-German Future Fund went through during its almost 20 years of functioning. The first part the author dedicated to theoretical concepts, which shed light on study of the Czech-German Future Fund. These theoretical concepts are reconciliation and public diplomacy. Thereafter are in tis thesis described efforts to compensate victims of National Socialism in Czechoslovakia and in the Czech Republic. This part of thesis is followed by description of the Czech-German Future Fund and its history. Based on this German-Czech Declaration of Mutual Relations and their Future Development of 1997 was the fund's mission to compensate victims of National Socialism, who didn't receive a compensation until then. The fund fulfilled this mission after 10 years of its function and also went through by many changes during almost 10 years of its functioning. The author describes these changes on which is based description of the project policy development of Czech-German Future Fund. After that the diploma thesis concentrates on changes in individual fund project groups, which are supported by the fund. These changes have an impact on financial character of individual project groups, on change of their structure or on change of the place, where are individual...

Syftet med detta examensarbete är att göra en jämförande studie mellan faktorerna som enligt en teoretisk ram påverkar en miljöinvestering och faktorerna som ingår i ett företags bedömnings-modell. Respondentbolaget begärde i ett tidigt skede att få vara anonymt och benämns därför som Företaget. Det är en multinationell koncern med verksamhet i många skilda branscher, men med fokus på norden och produkter som kan kopplas till lantbruk. Den teoretiska referensramen har sin utgångspunkt i begreppen värde och investering samt hur deras koppling till miljö och miljöinvesteringar för att identifiera de faktorer som påverkar en miljöinvestering. Faktorerna som ingår i den teoretiska referensramen och som jämförs mot respondentbolagets faktorer är:  Investeringens värdetillförsel  Investeringens miljöpåverkan  Hur investeringen påverkar produktionsförutsättningarna  Krav från samhället  Kundkrav Kopplingen däremellan bedöms enligt en femgradig skala. Informationen från Företaget inhäm-tades genom semi-strukturerade intervjuer med representanter från Företaget. Slutsatsen för detta arbete är att Företaget har identifierat samma faktorer som den teoretiska referensramen. De använder dock mätetal som inte fullt ut reflekterar faktorerna. Den största avvikelsen är bedömningen av en investerings värdetillförsel, då Företaget fullt ut införlivar det producerade värdet samt det faktum att en miljöinvestering skall ses som irreversibel. Enkelhet premieras hos Företaget och det är för att prioritera modellens användbarhet, som Företaget väl-jer att acceptera brister i bedömningsmodellen. För att förbättra bedömningsmodellen bör Företaget därför införliva nya mätetal som till större del reflekterar faktorerna som påverkar en miljöinvestering / The purpose of this master thesis is to present a comparison between the factors that affects an environmental investment. This is done through applying a theoretical framework on the factors affecting a company’s existing appraisal model for environmental investments. The company that was a part of this thesis asked at an initial stage for confidentiality, therefore it is called the Company in this thesis. The Company that contributes with the appraisal model is a multination-al group with operations in many different industries, but with a focus on the Nordic countries and products that may be linked to the agricultural sector. The theoretical framework has its base in the concepts of value and investments and their connection to the environment and the envi-ronmental investment. The identified factors in the theoretical framework are:  The investment’s addition to the value creation to the company  The investment’s environmental impact  How the investment affects the production  Demands from society  Customer demands From these, the factors affecting a company’s existing appraisal model were compared and their connection to theoretical framework was judged according to a 5-grade scale. Information from the Company was acquired through semi-structured interviews with representatives from the Company. The largest deviation is how the company considers an investment’s contribution to the produced value. Because of this imperfection does the company's model not fully incorporate the produced value and that an environmental investment is irreversible. The overall conclusion is that the Company has identified the same factors as the theoretical framework. The Company has though chosen to use their existing methods and performance indicators that don’t fully incorporate the factors in the theoretical framework. The largest devia-tions are how the company considers an investment’s contribution to the produced value and that it should be considered as irreversible. The Company must therefore in order to enhance their appraisal model develop new performance measures for the factors.

This thesis addresses critical conceptions of Scottish literary development in the twentieth-century which inscribe realism as both the authenticating tradition and necessary telos of modern Scottish writing. To this end I identify and explore a Scottish ‘counter-tradition’ of modern uncanny fiction. Drawing critical attention to techniques of modal disruption in the works of a number of post-1970s Scottish writers gives cause to reconsider that realist teleology while positing a range of other continuities and tensions across modern Scottish literary history. The thesis initially defines the critical context for the project, considering how realism has come to be regarded as a medium of national literary representation. I go on to explore techniques of modal disruption and uncanny in texts by five Scottish writers, contesting ways in which habitual recourse to the realist tradition has obscured important aspects of their work. Chapter One investigates Ali Smith’s reimagining of ‘the uncanny guest’. While this trope has been employed by earlier Scottish writers, Smith redesigns it as part of a wider interrogation of the hyperreal twenty-first-century. Chapter Two considers two texts by James Robertson, each of which, I argue, invokes uncanny techniques familiar to readers of James Hogg and Robert Louis Stevenson in a way intended specifically to suggest concepts of national continuity and literary inheritance. Chapter Three argues that James Kelman’s political stance necessitates modal disruption as a means of relating intimate individual experience. Re-envisaging Kelman as a writer of the uncanny makes his central assimilation into the teleology of Scottish realism untenable, complicating the way his work has been positioned in the Scottish canon. Chapter Four analyses A.L. Kennedy’s So I Am Glad, delineating a similarity in the processes of repetition which result in both uncanny effects and the phenomenon of tradition, leading to Kennedy’s identification of an uncanny dimension in the concept of national tradition itself. Chapter Five considers the work of Alan Warner, in which the uncanny appears as an unsettling sense of significance embedded within the banal everyday, reflecting an existentialism which reaches beyond the national. In this way, I argue that habitual recourse to an inscribed realist tradition tends to obscure the range, complexity and instability of the realist techniques employed by the writers at issue, demonstrating how national continuities can be productively accommodated within wider, pluralistic analytical approaches.

O Vírus da Imunodeficiência Humana (HIV) é o agente etiológico da Síndrome da Imunodeficiência Adquirida (AIDS). A AIDS é uma doença de distribuição mundial, e estima-se que existam atualmente pelo menos 36,9 milhões de pessoas infectadas com o vírus. Durante o seu ciclo replicativo, o HIV promove diversas alterações na fisiologia da célula hospedeira a fim de promover sua sobrevivência e potencializar a replicação. A rápida progressão da infecção pelo HIV-1 em humanos e em modelos animais está intimamente ligada à função da proteína acessória Nef. Dentre as diversas ações de Nef está a regulação negativa de proteínas importantes na resposta imunológica, como o receptor CD4. Sabe-se que esta ação resulta da indução da degradação de CD4 em lisossomos, mas os mecanismos moleculares envolvidos ainda são totalmente elucidados. Nef forma um complexo tripartite com a cauda citosólica de CD4 e a proteína adaptadora 2 (AP-2), em vesículas revestidas por clatrina nascentes, induzindo a internalização e degradação lisossomal de CD4. Pesquisas anteriores demonstraram que o direcionamento de CD4 aos lisossomos por Nef envolve a entrada do receptor na via dos corpos multivesiculares (MVBs), por um mecanismo atípico, pois, embora não necessite da ubiquitinação de carga, depende da ação de proteínas que compõem os ESCRTs (Endosomal Sorting Complexes Required for Transport) e da ação de Alix, uma proteína acessória da maquinaria ESCRT. Já foi reportado que Nef interage com subunidades dos complexos AP-1, AP-2, AP-3 e Nef não parece interagir com subunidades de AP-4 e AP-5. Entretanto, o papel da interação de Nef com AP-1 e AP-3 na regulação negativa de CD4 ainda não está totalmente elucidado. Ademais, AP-1, AP-2 e AP-3 são potencialmente heterogêneos devido à existência de isoformas múltiplas das subunidades codificadas por diferentes genes. Todavia, existem poucos estudos para demonstrar se as diferentes combinações de isoformas dos APs são formadas e se possuem propriedades funcionais distintas. O presente trabalho procurou identificar e caracterizar fatores celulares envolvidos na regulação do tráfego intracelular de proteínas no processo de regulação negativa de CD4 induzido por Nef. Mais especificamente, este estudo buscou caracterizar a participação do complexo AP-1 na modulação negativa de CD4 por Nef de HIV-1, através do estudo funcional das duas isoformas de ?-adaptina, subunidades de AP-1. Utilizando a técnica de Pull-down demonstramos que Nef é capaz de interagir com ?2. Além disso, nossos dados de Imunoblot indicaram que a proteína ?2-adaptina, e não ?1-adaptina, é necessária no processo de degradação lisossomal de CD4 por Nef e que esta participação é conservada para degradação de CD4 por Nef de diferentes cepas virais. Ademais, por citometria de fluxo, o silenciamento de ?2, e não de ?1, compromete a diminuição dos níveis de CD4 por Nef da membrana plasmática. A análise por imunofluorêsncia indireta também revelou que a diminuição dos níveis de ?2 impede a redistribuição de CD4 por Nef para regiões perinucleares, acarretando no acúmulo de CD4, retirados por Nef da membrana plasmática, em endossomos primários. A depleção de ?1A, outra subunidade de AP-1, acarretou na diminuição dos níveis celulares de ?2 e ?1, bem como, no comprometimento da eficiente degradação de CD4 por Nef. Além disso, foi possível observar que, ao perturbar a maquinaria ESCRT via super-expressão de HRS (uma subunidade do complexo ESCRT-0), ocorreu um acumulo de ?2 em endossomos dilatados contendo HRS-GFP, nos quais também detectou-se CD4 que foi internalizado por Nef. Em conjunto, os resultados indicam que ?2-adaptina é uma importante molécula para o direcionamento de CD4 por Nef para a via ESCRT/MVB, mostrando ser uma proteína relevante no sistema endo-lisossomal. Ademais, os resultados indicaram que as isoformas ?-adaptinas não só possuem funções distintas, mas também parecem compor complexos AP-1 com diferentes funções celulares, já que apenas a variante AP-1 contendo ?2, mas não ?1, participa da regulação negativa de CD4 por Nef. Estes estudos contribuem para o melhor entendimento dos mecanismos moleculares envolvidos na atividade de Nef, que poderão também ajudar na melhor compreensão da patogênese do HIV e da síndrome relacionada. Em adição, este trabalho contribui para o entendimento de processos fundamentais da regulação do tráfego de proteínas transmembrana no sistema endo-lisossomal. / The Human Immunodeficiency Virus (HIV) is the etiologic agent of Acquired Immunodeficiency Syndrome (AIDS). AIDS is a disease which has a global distribution, and it is estimated that there are currently at least 36.9 million people infected with the virus. During the replication cycle, HIV promotes several changes in the physiology of the host cell to promote their survival and enhance replication. The fast progression of HIV-1 in humans and animal models is closely linked to the function of an accessory protein Nef. Among several actions of Nef, one is the most important is the down-regulation of proteins from the immune response, such as the CD4 receptor. It is known that this action causes CD4 degradation in lysosome, but the molecular mechanisms are still incompletely understood. Nef forms a tripartite complex with the cytosolic tail of the CD4 and adapter protein 2 (AP-2) in clathrin-coated vesicles, inducing CD4 internalization and lysosome degradation. Previous research has demonstrated that CD4 target to lysosomes by Nef involves targeting of this receptor to multivesicular bodies (MVBs) pathway by an atypical mechanism because, although not need charging ubiquitination, depends on the proteins from ESCRTs (Endosomal Sorting Complexes Required for Transport) machinery and the action of Alix, an accessory protein ESCRT machinery. It has been reported that Nef interacts with subunits of AP- 1, AP-2, AP-3 complexes and Nef does not appear to interact with AP-4 and AP-5 subunits. However, the role of Nef interaction with AP-1 or AP-3 in CD4 down-regulation is poorly understood. Furthermore, AP-1, AP-2 and AP-3 are potentially heterogeneous due to the existence of multiple subunits isoforms encoded by different genes. However, there are few studies to demonstrate if the different combinations of APs isoforms are form and if they have distinct functional properties. This study aim to identify and characterize cellular factors involved on CD4 down-modulation induced by Nef from HIV-1. More specifically, this study aimed to characterize the involvement of AP-1 complex in the down-regulation of CD4 by Nef HIV-1 through the functional study of the two isoforms of ?-adaptins, AP-1 subunits. By pull-down technique, we showed that Nef is able to interact with ?2. In addition, our data from immunoblots indicated that ?2- adaptin, not ?1-adaptin, is required in Nef-mediated targeting of CD4 to lysosomes and the ?2 participation in this process is conserved by Nef from different viral strains. Furthermore, by flow cytometry assay, ?2 depletion, but not ?1 depletion, compromises the reduction of surface CD4 levels induced by Nef. Immunofluorescence microscopy analysis also revealed that ?2 depletion impairs the redistribution of CD4 by Nef to juxtanuclear region, resulting in CD4 accumulation in primary endosomes. Knockdown of ?1A, another subunit of AP-1, resulted in decreased cellular levels of ?1 and ?2 and, compromising the efficient CD4 degradation by Nef. Moreover, upon artificially stabilizing ESCRT-I in early endosomes, via overexpression of HRS, internalized CD4 accumulates in enlarged HRS-GFP positive endosomes, where co-localize with ?2. Together, the results indicate that ?2-adaptin is a molecule that is essential for CD4 targeting by Nef to ESCRT/MVB pathway, being an important protein in the endo-lysosomal system. Furthermore, the results indicate that ?-adaptins isoforms not only have different functions, but also seem to compose AP-1 complex with distinct cell functions, and only the AP-1 variant comprising ?2, but not ?1, acts in the CD4 down-regulation induced by Nef. These studies contribute to a better understanding on the molecular mechanisms involved in Nef activities, which may also help to improve the understanding of the HIV pathogenesis and the related syndrome. In addition, this work contributes with the understanding of primordial process regulation on intracellular trafficking of transmembrane proteins.

Submitted by Noeme Timbo (noeme.timbo@metodista.br) on 2016-09-14T18:52:33Z No. of bitstreams: 1 IGORMARQUES.pdf: 1484987 bytes, checksum: 222e9ad06f9f0aead873e9543fe463b9 (MD5) / Made available in DSpace on 2016-09-14T18:52:33Z (GMT). No. of bitstreams: 1 IGORMARQUES.pdf: 1484987 bytes, checksum: 222e9ad06f9f0aead873e9543fe463b9 (MD5) Previous issue date: 2015-08-27 / Against the backdrop of the denominational status of network Adventist education present in a remarkable way in the school space and the intense religious diversity students, this research analyzes the relationship of possible tensions between the denominational school status and religious diversity present. It takes into account the process of modernity causing significant change in education, in religion and in the form of the two institutes relate to each other. It took into account the socio-economic and religious profile of the students and how is the reception of religious education in Adventist school space, including students who declare themselves Adventists. The area chosen for this research was the Adventist schools located in the ABCD Paulista context, which offer high school. These school units are located in the cities of Diadema, Santo Andre and Sao Caetano do Sul, cities located in the same micro region, but with different socioeconomic realities. / Tendo como pano de fundo a confessionalidade da rede adventista de educação presente de maneira marcante no espaço escolar e a intensa diversidade religiosa discente, esta pesquisa analisa a relação de possíveis tensões entre a confessionalidade escolar e a diversidade religiosa presente neste espaço. Leva em consideração o processo de modernidade causadora de importantes transformações na educação, na religião e na forma dos dois institutos se relacionarem. Levou-se em consideração o perfil socioeconômico e religioso dos alunos e possíveis tensões na recepção do religioso no espaço escolar adventista por parte dos discentes, inclusive por aqueles que se declaram adventistas. O espaço escolhido para esta pesquisa foi o de colégios adventistas localizadas no contexto do ABCD Paulista, que ofertam o Ensino Médio. Estas unidades escolares estão situadas nas cidades de Diadema, Santo André e São Caetano do Sul, cidades localizadas na mesma microrregião, mas com distintas realidades socioeconômicas.

This diploma thesis is focused on the evaluation of six selected zoonoses with the occurrence in South Bohemia (campylobacteriosis, salmonellosis, listeriosis, tick-borne meningoencephalitis, Lyme borreliosis, tularemia) between the years 2003-2013. Campylobacteriosis and salmonellosis were evaluated the most common zoonoses in the South Bohemian Region during the monitored period. Their common feature is the alimentary transmission. Between 2003 to 2008 salmonellosis recorded the highest number of reported cases, on the contrary, campylobacteriosis has reported the highest number of occurrences since 2008. District of Czech Budweis showed the highest incidence of both zoonoses during the monitored period (4,139 cases of salmonellosis and 4,924 cases of campylobacteriosis). Another but not less important zoonotic is tick-borne meningoencephalitis, which incidence had the highest number in South Bohemian Region of all the regions of Czech Republic. The second part of the thesis is based on questionnaire studies focused on awareness of zoonoses and the issue of resistance and overuse of antibiotics. In total 479 questionnaires were evaluated. The survey findings may be equally described as interesting and positive, since the respondents had considerable awareness of the issue of antibiotic resistance.

O Vírus da Imunodeficiência Humana (HIV) é o agente etiológico da Síndrome da Imunodeficiência Adquirida (AIDS). A AIDS é uma doença de distribuição mundial, e estima-se que existam atualmente pelo menos 36,9 milhões de pessoas infectadas com o vírus. Durante o seu ciclo replicativo, o HIV promove diversas alterações na fisiologia da célula hospedeira a fim de promover sua sobrevivência e potencializar a replicação. A rápida progressão da infecção pelo HIV-1 em humanos e em modelos animais está intimamente ligada à função da proteína acessória Nef. Dentre as diversas ações de Nef está a regulação negativa de proteínas importantes na resposta imunológica, como o receptor CD4. Sabe-se que esta ação resulta da indução da degradação de CD4 em lisossomos, mas os mecanismos moleculares envolvidos ainda são totalmente elucidados. Nef forma um complexo tripartite com a cauda citosólica de CD4 e a proteína adaptadora 2 (AP-2), em vesículas revestidas por clatrina nascentes, induzindo a internalização e degradação lisossomal de CD4. Pesquisas anteriores demonstraram que o direcionamento de CD4 aos lisossomos por Nef envolve a entrada do receptor na via dos corpos multivesiculares (MVBs), por um mecanismo atípico, pois, embora não necessite da ubiquitinação de carga, depende da ação de proteínas que compõem os ESCRTs (Endosomal Sorting Complexes Required for Transport) e da ação de Alix, uma proteína acessória da maquinaria ESCRT. Já foi reportado que Nef interage com subunidades dos complexos AP-1, AP-2, AP-3 e Nef não parece interagir com subunidades de AP-4 e AP-5. Entretanto, o papel da interação de Nef com AP-1 e AP-3 na regulação negativa de CD4 ainda não está totalmente elucidado. Ademais, AP-1, AP-2 e AP-3 são potencialmente heterogêneos devido à existência de isoformas múltiplas das subunidades codificadas por diferentes genes. Todavia, existem poucos estudos para demonstrar se as diferentes combinações de isoformas dos APs são formadas e se possuem propriedades funcionais distintas. O presente trabalho procurou identificar e caracterizar fatores celulares envolvidos na regulação do tráfego intracelular de proteínas no processo de regulação negativa de CD4 induzido por Nef. Mais especificamente, este estudo buscou caracterizar a participação do complexo AP-1 na modulação negativa de CD4 por Nef de HIV-1, através do estudo funcional das duas isoformas de ?-adaptina, subunidades de AP-1. Utilizando a técnica de Pull-down demonstramos que Nef é capaz de interagir com ?2. Além disso, nossos dados de Imunoblot indicaram que a proteína ?2-adaptina, e não ?1-adaptina, é necessária no processo de degradação lisossomal de CD4 por Nef e que esta participação é conservada para degradação de CD4 por Nef de diferentes cepas virais. Ademais, por citometria de fluxo, o silenciamento de ?2, e não de ?1, compromete a diminuição dos níveis de CD4 por Nef da membrana plasmática. A análise por imunofluorêsncia indireta também revelou que a diminuição dos níveis de ?2 impede a redistribuição de CD4 por Nef para regiões perinucleares, acarretando no acúmulo de CD4, retirados por Nef da membrana plasmática, em endossomos primários. A depleção de ?1A, outra subunidade de AP-1, acarretou na diminuição dos níveis celulares de ?2 e ?1, bem como, no comprometimento da eficiente degradação de CD4 por Nef. Além disso, foi possível observar que, ao perturbar a maquinaria ESCRT via super-expressão de HRS (uma subunidade do complexo ESCRT-0), ocorreu um acumulo de ?2 em endossomos dilatados contendo HRS-GFP, nos quais também detectou-se CD4 que foi internalizado por Nef. Em conjunto, os resultados indicam que ?2-adaptina é uma importante molécula para o direcionamento de CD4 por Nef para a via ESCRT/MVB, mostrando ser uma proteína relevante no sistema endo-lisossomal. Ademais, os resultados indicaram que as isoformas ?-adaptinas não só possuem funções distintas, mas também parecem compor complexos AP-1 com diferentes funções celulares, já que apenas a variante AP-1 contendo ?2, mas não ?1, participa da regulação negativa de CD4 por Nef. Estes estudos contribuem para o melhor entendimento dos mecanismos moleculares envolvidos na atividade de Nef, que poderão também ajudar na melhor compreensão da patogênese do HIV e da síndrome relacionada. Em adição, este trabalho contribui para o entendimento de processos fundamentais da regulação do tráfego de proteínas transmembrana no sistema endo-lisossomal. / The Human Immunodeficiency Virus (HIV) is the etiologic agent of Acquired Immunodeficiency Syndrome (AIDS). AIDS is a disease which has a global distribution, and it is estimated that there are currently at least 36.9 million people infected with the virus. During the replication cycle, HIV promotes several changes in the physiology of the host cell to promote their survival and enhance replication. The fast progression of HIV-1 in humans and animal models is closely linked to the function of an accessory protein Nef. Among several actions of Nef, one is the most important is the down-regulation of proteins from the immune response, such as the CD4 receptor. It is known that this action causes CD4 degradation in lysosome, but the molecular mechanisms are still incompletely understood. Nef forms a tripartite complex with the cytosolic tail of the CD4 and adapter protein 2 (AP-2) in clathrin-coated vesicles, inducing CD4 internalization and lysosome degradation. Previous research has demonstrated that CD4 target to lysosomes by Nef involves targeting of this receptor to multivesicular bodies (MVBs) pathway by an atypical mechanism because, although not need charging ubiquitination, depends on the proteins from ESCRTs (Endosomal Sorting Complexes Required for Transport) machinery and the action of Alix, an accessory protein ESCRT machinery. It has been reported that Nef interacts with subunits of AP- 1, AP-2, AP-3 complexes and Nef does not appear to interact with AP-4 and AP-5 subunits. However, the role of Nef interaction with AP-1 or AP-3 in CD4 down-regulation is poorly understood. Furthermore, AP-1, AP-2 and AP-3 are potentially heterogeneous due to the existence of multiple subunits isoforms encoded by different genes. However, there are few studies to demonstrate if the different combinations of APs isoforms are form and if they have distinct functional properties. This study aim to identify and characterize cellular factors involved on CD4 down-modulation induced by Nef from HIV-1. More specifically, this study aimed to characterize the involvement of AP-1 complex in the down-regulation of CD4 by Nef HIV-1 through the functional study of the two isoforms of ?-adaptins, AP-1 subunits. By pull-down technique, we showed that Nef is able to interact with ?2. In addition, our data from immunoblots indicated that ?2- adaptin, not ?1-adaptin, is required in Nef-mediated targeting of CD4 to lysosomes and the ?2 participation in this process is conserved by Nef from different viral strains. Furthermore, by flow cytometry assay, ?2 depletion, but not ?1 depletion, compromises the reduction of surface CD4 levels induced by Nef. Immunofluorescence microscopy analysis also revealed that ?2 depletion impairs the redistribution of CD4 by Nef to juxtanuclear region, resulting in CD4 accumulation in primary endosomes. Knockdown of ?1A, another subunit of AP-1, resulted in decreased cellular levels of ?1 and ?2 and, compromising the efficient CD4 degradation by Nef. Moreover, upon artificially stabilizing ESCRT-I in early endosomes, via overexpression of HRS, internalized CD4 accumulates in enlarged HRS-GFP positive endosomes, where co-localize with ?2. Together, the results indicate that ?2-adaptin is a molecule that is essential for CD4 targeting by Nef to ESCRT/MVB pathway, being an important protein in the endo-lysosomal system. Furthermore, the results indicate that ?-adaptins isoforms not only have different functions, but also seem to compose AP-1 complex with distinct cell functions, and only the AP-1 variant comprising ?2, but not ?1, acts in the CD4 down-regulation induced by Nef. These studies contribute to a better understanding on the molecular mechanisms involved in Nef activities, which may also help to improve the understanding of the HIV pathogenesis and the related syndrome. In addition, this work contributes with the understanding of primordial process regulation on intracellular trafficking of transmembrane proteins.

Text in English and Arabic / In pre-colonial Africa, the Southwestern Sahara which includes Mauritania, Mali and Senegal belonged to what was then referred to as the Sudan and extended from the Atlantic seaboard to the Red Sea. The advent of Islam and the Arabic language to West Africa in the 11th century heralded an intellectual marathon whose literary output still fascinates us today. At a time when Europe was emerging from the dark ages and Africa was for most Europeans a terra incognita, indigenous African scholars were composing treatises as diverse as mathematics, agriculture and the Islamic sciences. A twentieth century Mauritanian, Arabic monograph, Irshād al- Muqallidīn ʿinda ikhtilāf al-Mujtahidīn1, written circa 1910/1332, by a yet unknown Mauritanian jurist of the Mālikī School, Bāba bin al-Shaykh Sīdī al- Shinqīṭī al-Ntishā-ī (d.1920/1342), a member of the muchacclaimed Shinqīṭī fraternity of scholars, is a fine example of African literary accomplishment. This manuscript hereinafter referred to as the Irshād, is written within the legal framework of Islamic jurisprudence (usūl al-fiqh). A science that relies for the most part on the intellectual and interpretive competence of the independent jurist, or mujtahid, in the application of the methodologies employed in the extraction of legal norms from the primary sources of the sharīʿah. The subject matter of the Irshād deals with the question of juristic differences. Juristic differences invariably arise when a mujtahid exercises his academic freedom to clarify or resolve conundrums in the law and to postulate legal norms. Other independent jurists (mujtahidūn) may posit different legal norms because of the exercise of their individual interpretive skills. These differences, when they are deemed juristically irreconcilable, are called ikhtilāfāt (pl. of ikhtilāf). The author of the Irshād explores a corollary of the ikhtilāf narrative and posits the hypothesis that there ought not to be ikhtilāf in the sharīʿah. The proposed research will comprise an annotated translation of the monograph followed by a synopsis and commentary on its dominant themes. / Religious Studies and Arabic / D. Litt. et Phil. (Islamic Studies)