Titre de l'écran-titre (visionné le 23 octobre 2023) / La maladie de Huntington (MH) est une pathologie neurodégénérative caractérisée par une mutation de la protéine Huntingtine (HTT). Cette maladie se caractérise par des symptômes moteurs, ainsi que des troubles cognitifs. Au niveau moléculaire, la HTT se dote d'une queue polyQ plus longue qu'en condition physiologique, et à tendance à s'agréger. Ces amas protéiques vont perturber le fonctionnement cellulaire, en particulier celui des neurones dopaminergiques du striatum. Au sein de ces cellules, des altérations transcriptionnelles de nombreux microARNs (miR) sont observées. Les miR sont de petits ARNs non codants capables de réguler à la baisse la transcription de nombreux ARNm différents. Notamment, le miR-132 est fortement impliqué dans la survie neuronale, et les processus cognitifs, deux éléments principalement altérés dans la MH. Or, il s'avère que le miR-132 se trouve être diminué chez les patients atteints de la MH. Notre hypothèse est donc que la perte du miR-132 explique, au moins en partie, les symptômes liés à la MH. Le but de cette étude est donc de comprendre comment et à quel point le miR-132 agit dans le cadre de la MH. Afin de tester l'hypothèse, nous avons généré quatre génotypes de souris à partir de lignées contrôles et des souris zQ/175, modèle de la MH. Dans ces deux lignées, nous avons effectué une délétion à l'aide du système Cre/Lox du gène du miR-132, afin d'étudier le rôle de ce miR en condition physiologique et pathologique. À cette fin, nous avons étudié l'impact de la délétion du miR-132 au niveau transcriptionnel, protéique, physiologique et comportemental. Après avoir validé notre modèle de la MH, nous avons pu constater que les symptômes comportementaux, en particulier l'anxiété mesurée en terrain ouvert, étaient aggravés significativement chez les souris sans miR-132. Par la suite, pour pouvoir réaliser des analyses biochimiques, nous avons prélevé de nombreux tissus afin de couvrir un large champ d'étude. Dans cette étude, nous nous intéresserons aux régions du striatum (épicentre de la maladie), du cortex (contrôle au sein du SNC) et du cœur (contrôle extérieur au SNC). Nous avons observé que la transcription de nombreux ARNm était altérée de manière similaire chez les souris sans le miR-132 et les souris MH. Au niveau protéique, nous avons validé l'augmentation de la forme agrégée de HTT dans nos modèles MH, avec ou sans miR-132, au sein du cortex et du striatum. Cependant, aucune différence claire n'a pu être observé pour des protéines impliquées dans la survie neuronale ou identifiées en tant que cible du miR-132. Nos résultats préliminaires laissent supposer que de multiples voies compensatoires se mettent en place lors d'une perte du miR-132. Une analyse plus poussée des voies dérégulées au niveau transcriptionnel nous permettrait d'isoler, puis de mettre en évidence le mécanisme d'interaction indirect entre le miR-132 et HTT. À partir de là, il serait possible de mieux comprendre comment le miR-132 agit sur les altérations comportementales observées chez nos souris. Une fois ces mécanismes identifiés, nous pourrions mieux comprendre cette pathologie et réussir à trouver des traitements efficaces.

The wane of the North American Fur Trade (ca. 1800-1850) was the result of resource depletion, military action, social unrest, increased European settlement and the increased proximity of diverse cultural groups. The effects of these occurrences upon the residents of Aussom Cabin Site have been analyzed. Both historical and archaeological analyses were utilized, offering a verified and accurate account of the demise of the fur trade and its effect upon a specific population.Attention is paid to the development of the fur trade industry, as well as to the manner in which it affected regional lifeways. The location of the Aussom Cabin, both chronologically and socially, within this process has been explicated. The chain of occupation at the site has been established, the morphology of the cabin, and the lifeways of its inhabitants have been surmised. The manner in which the cabin was razed and the depositional integrity of the Aussom Cabin have also been determined. / Department of Anthropology

Ce mémoire propose une étude à la croisée du religieux et du politique mettant en parallèle la pensée du pape Benoît XVI avec la théorie du Choc des civilisations de Samuel Huntington. L'analyse des écrits de ce pape théologien fait ressortir son approche critique de la modernité et de l'héritage des lumières, dans un contexte de crise culturelle et spirituelle de l'Occident. Dans une époque marquée par une dynamique interculturelle aussi incontournable qu'imprévisible, Benoît XVI se révèle un ardent défenseur d'une réconciliation entre la raison sécularisée et la foi chrétienne au sein de la culture occidentale. Contrairement à Huntington qui développe une grille de lecture où l'élément religieux représente le mur ultime séparant les grands ensembles culturels du monde, Benoît XVI affirme que l'ouverture à la vérité, présente dans chaque grande tradition religieuse de l'humanité, permet, en principe, une rencontre positive entre celles-ci. Ainsi, le Saint-Père considère que ce n'est pas la religion, mais plutôt le renoncement à la recherche de la vérité sur l'homme et sur Dieu qui représente l'obstacle le plus grand à la rencontre interculturelle. Enfin, alors qu'Huntington préconise un renoncement définitif à l'universalité des valeurs occidentales, Benoît XVI prend plutôt le pari d'un renoncement à l'universalité illusoire de la « civilisation technologique » pour redécouvrir le sens véritable de la fraternité chrétienne à l'échelle de l'humanité. Ce mémoire conclut donc que s'il existe une convergence entre les deux approches quant à l'importance de la religion et de la culture dans les relations entre les peuples et les états, des divergences fondamentales existent, tant au niveau de la perspective historique, anthropologique et philosophique que des orientations pratiques. Ceci permet d'affirmer que l'approche interculturelle de Benoît XVI ne peut pas être interprétée comme étant une approche huntingtonienne.

Abstract Syfte: Studien grundar sig på ett problemområde gällande uteslutandet av kvinnlig rösträtt i demokratimätningar. Syftet är att undersöka hur demokratimått förändras när kvinnlig rösträtt tas med i mätningarna. Studien analyserar två klassiker inom demokratiforskning, Seymour Lipset (1959) och Samuel P. Huntington (1991) samt tre modernare demokratimått (Democracy index, BMR, Polity IV Revised combined score).   Teori: Studien utgår ifrån en teori hämtad från Pamela Paxton (1995). Teorin handlar om konsekvenser och kritik mot demokratiforskare som uteslutit kvinnlig rösträtt i mått på demokrati.   Metod: En kvantitativ metod i form av statistisk dataanalys har använts. Med hjälp av tidsserier har jämförelser över införandet av demokrati samt kvinnlig rösträtt genomförts.   Resultat: Resultatet visar att Paxtons kritik är befogad samt bekräftar hennes teori och slutsatser. Införandet av kvinnlig rösträtt i ovannämnda demokratimått innebär en förändring för de studier där måtten har använts.   Nyckelord: kvinnlig rösträtt, demokrati, demokratisk transition, Huntington, Lipset, Paxton, women’s suffrage

Introduktion: Huntingtons sjukdom (HS) är en neurologisk sjukdom som är ärftlig. Sjukdomen påverkar hjärnans nervceller och ger symtom som ofrivilliga ryckningar i extremiteterna. Sväljsvårigheter och problem att formulera meningar är också något som medföljer sjukdomen. I ett senare stadie av sjukdomen är personen helt beroende av att få hjälp med vardagliga sysslor som att kliva upp, gå på toaletten och duscha. Anhöriga blir ofta vårdare åt den sjuka.  Syfte: Syftet med studien var att beskriva erfarenheter hos närstående till personer med HS, samt att beskriva undersökningsgrupperna ur de valda artiklarna som använts i föreliggande studie.  Metod: Studien är en beskrivande litteraturstudie som är baserad på 11 vetenskapliga artiklar. Databaserna som använts för att hitta artiklar är PubMed och Cinahl.  Resultat: Partners till personer med HS anpassade sej till de nya förhållandena och övervägde ganska snabbt om de ville bli vårdare eller om de ville skiljas. Barn till föräldrar med HS hade inget val och fick ta mycket vuxenansvar i hemmet. Med sjukdomens progress blev vårdandet tyngre och närstående lade sitt eget liv ”på vänt”. Oron för framtiden hanterades genom att förneka eller att förbereda sej. Förståelse och hjälp fick närstående från andra i liknande situation. Sjukvården idag visste lite om sjukdomen och närståendes behov vilket skadade förtroendet. Slutsats: Närstående och anhörigvårdare upplevde en stor förändring i livet när sjukdomen blev värre. De kände oro och stress inför framtiden och deras relation till den sjuke förändrades med tiden. De möttes ofta av okunskap om sjukdomen. Anpassad information och stöttning längs vägen var något närstående önskade, men sällan fick uppleva. All tid och alla känslor gick åt att ta hand om och oroa sej för den sjuke. Rädslan för att gemensamma barn bar på genen var ständigt återkommande. / Introduction: Huntington’s disease (HD) is a genetic neurological disease. It affects the brains nerve cells. Symptoms include involuntary spasms, inability to swallow and difficulty putting together sentences. In the latter stages of the disease patients become completely dependent on help with everyday chores like getting out of bed, using the bathroom and showering. It’s very common for close family and relatives to become carers to the patients. Purpose: The aim of the study was to research the effects HD has on immediate family and carers of an HD patient, furthermore to describe the included scientific articles study group. Method: The study is a descriptive literature study based on 11 scientific articles. The databases used for research are: PubMed and Cinahl Results: Related parties that were partners to people with HD adapted themselves to the new conditions and considered, fairly quickly if they wanted to become a caregiver or if they wanted a divorce. Children of parents with HD had no choice and had to take a lot of adult responsibilities at home. With the progression of the disease, caring became heavier and relatives put their own lives "on hold". Concerns for the future were handled by denying or preparing. Understanding and the support was received from people in similar situations. Healthcare today know little about the disease and related parties' needs, which damaged confidence. Conclusion: Related parties and family caregivers experienced a big change in life when the disease got worse. They worried and were stressed about the future and their relationship to the patient changed with time. They often met ignorance about the disease. Adapted information and support along the way was something related parties desired, but rarely experienced. All time and emotions were spent, taking care of and worry about the sick. The fear of the children carrying the gene were constantly recurring.

Pas de résumé français / In this thesis, we investigated troubles of sentence processing in Huntington’s disease (HD) at earlystage, which represents a model of damage mainly confined to the striatum. The role of striatalstructures in sentence processing is agreed upon, but its nature is still controversial. Most studieshave reported a role of the striatum for complex sentences or more controlled processes withinsentence processing, but the interpretation of this pattern differs according to two main views.Some authors have proposed that striatal structures have a linguistic function restricted to somesub-processes of sentence processing, while others claim that the deficits detected depend on themodulation that executive function exerts on language and sentence processing. Here, we aimed atfilling the gap between these approaches by using a psycholinguistic perspective to investigate onthe one hand the role of executive functions, in particular, working memory, in sentenceprocessing, and on the other hand the nature of the linguistic discrepancies reported in associationto striatal lesions. We thus built experimental paradigms that allow dissociating fine-grainedlinguistic variations in healthy subjects, and transferred them to HD patients. The profile ofimpairment detected in our experiments showed that working memory and other sources ofcomplexity can interfere with sentence processing by decreasing accuracy, but an impairment ofspecific syntactic processes occurs when working memory is controlled for. The pattern of the finegrainedsyntactic impairment detected is consistent with a dissociation between more frequent/lesscontrolled (default) and less frequent/more controlled (non-default) procedures in sentenceprocessing. Additionally, we detected that this deficit occurs despite the fact that HD patients arestill able to process syntactic information, suggesting that striatal structures spare syntacticrepresentations while they are involved in correctly applying syntactic procedures in non-defaultcontexts. We propose that this pattern is explained by a role of striatal structures in selectingbetween competing alternatives during sentence processing, which results in an inability to adapt tothe sentence context for non-default procedures. This parallels the role of striatal structures for selecting between competing alternatives in order to adapt to the changing environment, as reportedin motor control and in other domains of cognition. Although the domain specificity of striatalinvolvement in language cannot be demonstrated, it is highly compatible with the results obtainedin this thesis. Hence, linguistic functions might be modulated by distinct cortico-striatal circuits: onthe one hand by selecting linguistic representations as a function of the context, and on the otherhand, by modulating performance in language through executive functions. The frameworkemerging from this work thus helps conciliating apparently incongruent findings reported in theliterature. Yet, future research should better characterize anatomo-functional correlates of thisproposal

The aim of this study was to examine in which way political actors affected the outcome of democratizations during the Third Wave of Democracy. Due to the variety of cases concerning democratization in the 20th century there have been a lot of different outcomes and explanations regarding the contributing aspects of the transition from authoritarian rule. This study was needed in order to analyze how and if explanations regarding political actors was a critical element in the difference of outcomes. This was done by analyzing two similar cases of democratization, but where the outcome differed. The two cases analyzed were Czechoslovakia and Croatia. The study uses theories and models developed by researchers in the area of democratization in order to analyze the chosen cases, especially a model developed by Samuel P. Huntington (1991). This model serves to explain the difference in outcome and categorizes the political actors in a variety of aspects to determine whether or not a democratization was possible. The analysis of the study shows that the political actors of the two cases differs in the aspect of categorization, but also in the way in which they act during the transition phase. This implies that explanations regarding actors effects on democratization may be important in understanding why the outcomes differ. However, since this study only analyses the most prominent actors in two cases of democratization by categorization of a single theoretical model it is impossible to say that the outcome of this analysis is accurate and that it can be generalised. The uncertainty of the conclusions therefore underlines the importance of further research in the area of democratization and the difference in outcome of the chosen cases.

No description available.

Thèse de doctorat : Neurosciences : Paris 12 : 2007. / Thèse uniquement consultable au sein de l'Université Paris 12 (Intranet). Titre provenant de l'écran-titre. Bibliogr. : 275 réf.

Huntington Disease (HD) is a dominantly inherited neurological disease attributed to a CAG expansion within the HD gene. The HD mutation gives rise to a polyglutamine expansion in exon 1 of the protein huntingtin (Htt). Since the discovery of the HD mutation in 1993, various HD gene mouse models have been developed to contain either fragments or full-length copies of the mutant HD gene. The existence of these HD mouse models enables focused therapeutic testing to develop potential treatments for HD. RNA interference (RNAi) therapy is a targeted gene silencing approach whereby synthetic RNA constructs are shuttled into the cell by viral vectors and used by the cell’s endogenous RNAi machinery to silence a gene of interest. RNAi therapy holds promise for mutant huntingtin (muHtt) allele-specific silencing as a treatment for HD. The purpose of this thesis was to develop the tools for pre-clinical testing of RNAi-mediated gene silencing of human muHtt in the YAC128 mouse model of HD. First, AAV serotypes were compared for delivery to striatal neurons, the neurons most affected in HD. From this work AAV serotype 1 was selected as the most effective serotype for construct delivery. Second, synthetic RNAi constructs including short-hairpin RNA (shRNA) and microRNA-based constructs (miR-shRNAs) were compared for silencing of human muHtt expression in vivo. Here, miR-shRNAs were found to have increased gene silencing and improved tolerance in avoiding immune activation compared to shRNAs. Alternatively, the shRNAs induced dramatic immune activation and morbidity in some cases. Ultimately these findings will contribute to a pre-clinical trial in YAC128 mice investigating Htt RNAi-mediated gene silencing in the treatment of HD, which is also discussed in this thesis. This future work provides proof-of-principle for muHtt allele-specific silencing as a treatment of HD.