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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
1

Etude des conséquences du chaulage sur la structure et le fonctionnement des communautés d’ectomycorrhizes des forêts des Vosges / Consequences of liming on the ectomycorrhizal community structure and functioning in the Vosges forests

Rineau, François 04 November 2008 (has links)
Le chaulage est en un apport de Ca et Mg utilisé pour corriger les carences en cations des arbres dûes à l’acidité du sol. Les ectomycorrhizes (ECMs) apportent à l’arbre des nutriments d’origine organique et inorganique. Le fonctionnement de la communauté d’ECMs dépend de la disponibilité des éléments dans le sol, qui est modifiée par le chaulage. Les objectifs de cette étude sont donc de mesurer l’impact du chaulage sur la structure et le fonctionnement des communautés d’ECMs de hêtre et d’épicéa dépérissants, et de déterminer leur rôle dans l’amélioration de la nutrition minérale de l’arbre. Les résultats montrent que le chaulage est le deuxième facteur de structuration de la communauté des carpophores après l’arbre hôte. Le chaulage réduit l’abondance de mycorrhizes de morphotypes acidophiles au profit d’autres plus ubiquistes (Clavulina cristata sous épicéa et Lactarius subdulcis sous hêtre), confinées dans l’horizon organominéral et spécialisées dans la sécrétion potentielle de glucuronidase et de laccase, respectivement. Le chaulage augmente la sécrétion potentielle d’oxalate des ECMs sous hêtre, qui dépend en grande partie de l’activité des mycorrhizes de Lactarius subdulcis. Ce morphotype joue sans doute un rôle important dans l’altération des minéraux, d’autant plus que l’on observe une plus grande quantité d’éléments minéraux stockée dans ses ECMs. La comparaison qualitative des propriétés du sol, du fonctionnement des communautés d’ECMs, et de la nutrition des hêtres suggère que les ECMs, en particulier Lactarius subdulcis, jouent un rôle dans l’amélioration de la santé des arbres via l’assimilation de Ca et Mg, mais ces effets varient selon le type de sol. / Liming is a forestry practice consisting in Ca and Mg amendment used to correct tree cation deficiency induced by soil acidity. Ectomycorrhizae (ECM) provides the tree with nutrients derived both from mineral and organic sources. The ECM community structure and functioning is closely linked to soil nutrient availability, which is considerably modified by liming. The aims of this study were to assess, in declining beech and spruce stands, the impact of liming on ECM community structure and functioning, and to determine if ECMs take part in the improvement of tree mineral nutrition. Results showed that liming was the second factor of sporocarp community structuration after tree host. Liming also decreased the abundance of ECM tips of acidophilic morphotypes and induced the dominance of more ubiquist ones (Clavulina cristata for spruce, Lactarius subdulcis for beech). These morphotypes were confined in the organomineral layer and specialized in the potential secretion of glucuronidase and laccase, respectively. For beech, liming significantly increased the potential oxalate secretion by ECMs, which highly depends on the activity of Lactarius subdulcis. This morphotype is thus suspected to play an important role in mineral weathering, all the more that it accumulated more nutrients in its mantle in the limed plots. Qualitative comparison of liming effects on soil properties, ECM community functioning and beech nutrition showed that ECMs, especially a single morphotype as Lactarius subdulcis, can play an important part in the improvement of tree health, especially concerning Ca and Mg uptake. Liming effects appeared to be site-specific depending on the soil fertility.
2

Equations fonctionnelles abéliennes et théorie des tissus

Pirio, Luc 15 December 2004 (has links) (PDF)
Dans la première partie de cette thèse, on étudie les équations fonctionnelles de la forme F1(U1)+...+Fn(U_n)=0 en les inconnues, lorsque les Ui sont des fonctions de deux variables données. <br /><br />Dans la seconde partie, on applique les résultats obtenus auparavant à l'étude des tissus plans de rang maximal.
3

Imagerie fonctionnelle par ultrasons de la rétine et des fonctions visuelles cérébrales / Functional ultrasound imaging of the retina and visual function

Gesnik, Marc 15 November 2017 (has links)
Ces travaux de thèse portent sur les récents progrès de l’imagerie fonctionnelle par ultrasons et ses nouvelles applications en ophtalmologie. Dans le cadre d’un projet mêlant physique des ondes, imagerie, neurosciences et ophtalmologie, nous avons appliqué cette technologie à l’imagerie du système visuel et à l’étude préclinique de thérapies le ciblant. Au cours de ce projet, nous avons accompagné nos études précliniques de progrès constants dans notre imagerie.Un dispositif permettant l’imagerie du cerveau en 3 dimensions a été conçu. Cette imagerie a été réalisée en temps réel, ou à une fréquence ultrasonore de 30 MHz grâce au procédé d’entrelacement. Grâce à une connaissance a priori de l’architecture vasculaire cérébrale et de l’effet Doppler, il est possible de réaliser une décomposition spectrale des écoulements sanguins cérébraux selon leurs vitesses et de leurs orientations.Ceci a permis une étude des fonctions visuelles du rat et du primate non-humain. Nous avons imagé la rétine du primate en Doppler de puissance, mais sa forte mobilité en fait un organe délicat à imager en imagerie fonctionnelle. En revanche, nous avons réalisé une imagerie fonctionnelle de la rétine de rat à 30 MHz. Nous avons caractérisé en détail le système visuel cérébral de ce rongeur. Nous avons mis en évidence ses principales structures et redémontré leurs caractéristiques les plus connues, comme leur organisation rétinotopique ou leur différence de temps de réponse neurovasculaire à un stimulus. Des animaux traités par des thérapies de restauration visuelle a été imagée. La première imagerie de primates non-humains anesthésiés puis éveillés et exécutant une tâche comportementale, et la détection de variations de flux sanguins dues à des erreurs uniques ont été réalisées. Enfin, une étude préclinique aiguë et une étude chronique de traitements ayant des effets neurovasculaires ont été menées grâce au suivi du flux sanguin par nos procédés. / This thesis focuses on recent improvements in the functional ultrasound imaging (fUS) technique and their applications in the field of ophthalmology. Within the framework of a synergetic project blending waves physics, medical imaging, neuroscience and ophthalmology, fUS was shown to be capable of imaging and studying the visual system of healthy and diseased animals for the purpose of preclinical studies. To tackle these issues, constant upgrades in the fUS technique had to support the preclinical studies.An experimental set-up was built to image the visual pathway in three dimensions with fUS. Using a new imaging facility, fUS was proven to be feasible in real time and at high ultrasound frequencies such as 30 MHz. Interleaved sampling had to be implemented in that case. Furthermore, the a priori knowledge of the vascular cerebral architecture and the Doppler Effect were exploited to spectrally decompose cerebral blood flux and vessels according to their velocities and orientations.Leveraging these improvements, functional ultrasound imaging of rats and non-human primates was performed. Primate retina was imaged with Power Doppler, but proved to be too mobile to be functionally imaged. However, fUS has been performed on rat retina after 30 MHz fUS imaging had been implemented. The rat visual pathway has then been characterised with fUS. Some of its known features where highlighted such as its retinotopic organisation or the time response differences between some of its structures. The same set-up has been leveraged to map the cerebral activity of animal that underwent visual restauration therapies. These tools were then used to map cerebral activity in anesthetized and awake and behaving monkeys. Unique blood volume variations due to unique mistakes were detected. These tools were finally applied to two preclinical trials on a depressive state of the brain vascular contractility. Blood volume and blood velocity changes were highlighted throughout an acute and a chronical study.
4

Identification des gènes controllant le syndrome lymphoproliferatif se developpant dans des souris depourvues de l'adaptateur lat / Identifying genes modulating lymphoproliferative disorder originating from lat deficiency in T cells

Liang, Yinming 19 September 2013 (has links)
Lat est clé dans le développement des cellules T. En l'absence de Lat, le développement des cellules T au niveau du thymus est complètement bloqué au stade DN3. Le développement des lymphocytes T est très diminué dans des souris knockin LatY136F dans lesquelles la tyrosine présente en position 136 de la protéine Lat est remplacée par une phénylalanine. De manière paradoxale, le petit nombre de cellules T qui émergent dans la périphérie des souris LatY136F donnent naissance à un syndrome lymphoprolifératif Th2 sévère. Ce projet vise à identifier les facteurs génétiques qui contribuent au développement d'un tel syndrome lymphoprolifératif. A la suite d'un crible génétique basée sur une mutagenèse à l'ENU (N-éthyl-N-nitrosurea), des lignées de souris mutantes LatY136F présentant une pathologie atténuée ou exacerbée ont été fixées et les mutations induites chimiquement ont été cartographiées et identifiées. En particulier, nous avons obtenu une lignée mutante appelée Basilic dépourvue du syndrome lymphoprolifératif. Le clonage positionnel assisté par les techniques de séquençage à haut-débit de l'ADN ont permis l'identification d'un gène appelé, Rltpr ou Lrrc16c, et ne possédant aucune fonction immunologique connue. Nous avons montré que Rltpr constitue un élément clé de la voie de signalisation opérée par la molécule de costimulation CD28. Les résultats principaux obtenus au cours de la thèse sont présentés sous forme d'un article publié. Un chapitre de perspective est consacré ensuite aux améliorations que nous pourrions apporter au type d'approche que nous avons réalisé. Enfin une dernière rubrique traite des outils permettant la manipulation du génome de la souris. / Lat is essential for proper T cell development. In the absence of Lat, intra thymic T cell development is completely blocked at an early stage known as the DN3 stage. LatY136F mice in which the tyrosine found at position 136 of Lat was replaced by a phenylalanine, also showed an impaired sequence of intrathymic T cell development. Paradoxically, the small number of improperly selected T cells that reach the periphery of LatY136F mice expand in an uncontrolled manner and trigger a severe Th2 lymphoproliferative disorder. The present thesis project aimed at identifying genetic factors contributing to the development of such a lymphoproliferative disorder. Using a sensitized ENU mutagenesis screen, we identified and characterized mutations that dampened or exacerbated the LatY136F pathology. A mutation that is called Basilic and that acts in a T cell intrinsic manner and completely prevented the LatY136F lymphoproliferative disorder was characterized in a comprehensive manner. Positional cloning assisted by next generation DNA sequencing demonstrated that Basilic corresponds to a mutation in a gene called Rltpr or Lrrc16c, the function of which was previously completely unknown in the frame of the immune system. Further functional studies performed during this project showed that Rltpr corresponded to a “missing link” involved in the signaling cascade that mediates the function of the co-stimulatory molecule CD28. Consistent with that view, nullozygous Cd28 mutant mice were found to be a phenocopy of the Basilic mice and as such prevented lymphoproliferative disorder in LatY136F mice. The Basilic mutation also resulted in a defect in regulatory T cell development.
5

Vers une comparaison métatranscriptomique entre deux sols alpins sous couvert nival contrasté / Towards a metatranscriptomic comparison between two alpine soils

Mustafa, Tarfa 28 September 2011 (has links)
La distribution de la neige à l'échelle du paysage dans les zones alpines est une des variables les plus importantes contrôlant la structure et la fonction des écosystèmes de montagne. Des changements d'épaisseur neigeuse et de durée d'enneigement peuvent entraîner de grands changements dans les conditions édapho-climatiques, ainsi que dans la composition des communautés végétales et surtout sur les cycles biogéochimiques majeurs et par conséquence la structure et le fonctionnement de l'écosystème. Nous avons utilisé l'approche métatranscriptomique pour essayer de comprendre la diversité fonctionnelle réelle et les activités exprimées dans les sols alpins par les micro-organismes, en réponse à différentes contraintes environnementales. La transcriptomique, et par extension, la métatranscriptomique, peut être vue comme l'analyse quantitative complète de tous les gènes exprimés par un ou plusieurs organismes, ou par l'écosystème entier. L'utilisation de cette approche implique d'abord l'extraction des ARN une bonne qualité et avec un bon rendement, ensuite la conversion de ces ARN en cDNA en ciblant les fractions de ARNm. La capacité d'évaluer le metatranscriptome des communautés microbiennes complexes dans différentes conditions environnementales représente en soi une avancée significative dans notre capacité de relier la structure et les fonctions des communautés avec les génotypes d'ADN (les séquences) et avec la correspondance phénotype. Dans cette étude, nous présentons l'utilisation pour la première fois de l'approche métatranscriptomique concernant les activités des communautés microbiennes des eucaryotes des sols alpins sous deux conditions d'enneigement très contrasté nommés LSM (lately snowmelt) et ESM (early snowmelt), qui sont caractérisés par des gradients climatiques contrastés et des différences de végétations associées. Nous présentons également une analyse des séquences et des procédures d'annotation en utilisant des logiciels publiquement disponibles et des scripts de python en utilisant l'environnent d'Obitools. Nous avons également développé un pipeline d'analyse bio-informatique adapté qui permet d'extraire correctement des renseignements fonctionnels et taxinomiques de ces bases de données. / The distribution of snow across the landscape in the Alps is one of the most important variables controlling the structure and function of mountain ecosystems. Changes in snow depth and duration can cause major changes in soil and climatic conditions, as well as the composition of plant communities and especially on the major biogeochemical cycles and consequently the structure and functioning of the ecosystem. We used the approach métatranscriptomique to try to understand the functional diversity and real activity expressed in Alpine soils by micro-organisms in response to different environmental constraints. Transcriptomics, and by extension, the métatranscriptomique, can be seen as full quantitative analysis of all genes expressed by one or more agencies or by the entire ecosystem. Using this approach involves first extracting RNA in good quality and good yield, then the conversion of RNA into cDNA by targeting mRNA fractions. The ability to assess metatranscriptome complex microbial communities under different environmental conditions is in itself a significant advance in our ability to link the structure and functions of communities with the genotypes of DNA (the sequence) and phenotype correspondence. In this study, we present the first use of the approach métatranscriptomique on the activities of eukaryotic microbial communities of alpine soil in two very contrasting locations called LSM (Lately snowmelt) and ESM (early snowmelt) which are characterized by contrasting climatic gradients and differences in vegetation associated. We present an analysis of sequences and annotation procedures using publicly available software and scripts using python programs and Obitools. We have also developed a pipeline of bioinformatics analysis adapted to correct extraction of information of the functional and taxonomic databases.
6

Role of plant rhizosphere across multiple species, grassland management and temperature on microbial communities and long term soil organic matter dynamics / Role of plant rhizosphere across multiple species, grassland management and temperature on microbial communities and long term soil organic matter dynamics

Shahzad, Tanvir 30 March 2012 (has links)
It is increasingly being recognized that the soil microbes can mineralize recalcitrant soil organic matter (SOM) by using the fresh carbon (C) as a source of energy, a process called priming effect (PE). It has been shown mostly in lab incubations that PE can have important consequences for sequestration of organic C in soils. However, the importance of PE in C and N dynamics of ecosystems remains little known. The soil-plant interactions and rhizospheric processes can modulate the rates of PE and its consequences on C and N dynamics in an ecosystem. The objective of this thesis was to determine the role of PE in the C and N dynamics of permanent grasslands and the modulation of this role in response to management (plant clipping, fertilization) and global warming. Moreover, it was aimed to identify the microbial groups involved in PE and to unravel the way, e.g. absorption of N, root exudations and litter deposition, by which plant can induce PE. The thesis was based on a new approach allowing continuous dual labelling of multiple grassland plants with 13C- and 14C-CO2. The dual labelling permitted the separation of soil-derived CO2 from plant-derived CO2, the calculation of PE and the determination of mean age of soil-derived CO2-C. Moreover, phospholipids fatty-acids analysis (PLFA) permitted to correlate the variation of PE with changes in microbial community composition. Our work showed that the increased SOM mineralization under grasses was consistently two to three times more than that in bare soils (i.e. PE) over long term (511 days). This reveals that the PE plays key role in ecosystem CO2-C flux and indicates that a very large pool of SOM is under the control of PE. Moreover, we report that 15,000 years old organic C from an undisturbed deep soil can be mineralized after the supply of fresh C by living plants to soil microbes. This result supports the idea that the SOM in deep soils is stable due to the energy-limitation of microbes and the ‘inert' pool of organic C defined in current models is not so ‘inert' finally. The supply of N in soil-plant system through the use of fertilizer or legume decreased the PE suggesting that the C storage in soils is limited by nutrient supply. Similarly, plant clipping reduced the plant N uptake thereby PE. Collectively these results suggest synchronization between plant N uptake and SOM mineralization supporting the idea that soils under permanent plant cover function as a bank of nutrients for the plant, maximizing plant productivity and nutrient retention. An innovative method clearly showed that the root exudation is the major way by which grassland plants induce PE. Moreover, saprophytic fungi are suggested as the key actors in the mineralization of recalcitrant SOM & PE. Lastly, we developed a new theory on temperature response of SOM mineralization by taking into account the energy-limitation of microbes and the temperature-dependent inactivation of enzymes. This theory predicts a negative relationship between temperature and mineralization of recalcitrant SOM, which was supported by experimental results. This finding challenges the classical paradigm of positive relationship between temperature and recalcitrant SOM mineralization. Overall, these investigations on plant-soil systems reinforce the idea that PE and underlying mechanisms play a key role in ecosystem C and N dynamics and even suggest that this role was underestimated in lab experiments. / It is increasingly being recognized that the soil microbes can mineralize recalcitrant soil organic matter (SOM) by using the fresh carbon (C) as a source of energy, a process called priming effect (PE). It has been shown mostly in lab incubations that PE can have important consequences for sequestration of organic C in soils. However, the importance of PE in C and N dynamics of ecosystems remains little known. The soil-plant interactions and rhizospheric processes can modulate the rates of PE and its consequences on C and N dynamics in an ecosystem. The objective of this thesis was to determine the role of PE in the C and N dynamics of permanent grasslands and the modulation of this role in response to management (plant clipping, fertilization) and global warming. Moreover, it was aimed to identify the microbial groups involved in PE and to unravel the way, e.g. absorption of N, root exudations and litter deposition, by which plant can induce PE. The thesis was based on a new approach allowing continuous dual labelling of multiple grassland plants with 13C- and 14C-CO2. The dual labelling permitted the separation of soil-derived CO2 from plant-derived CO2, the calculation of PE and the determination of mean age of soil-derived CO2-C. Moreover, phospholipids fatty-acids analysis (PLFA) permitted to correlate the variation of PE with changes in microbial community composition. Our work showed that the increased SOM mineralization under grasses was consistently two to three times more than that in bare soils (i.e. PE) over long term (511 days). This reveals that the PE plays key role in ecosystem CO2-C flux and indicates that a very large pool of SOM is under the control of PE. Moreover, we report that 15,000 years old organic C from an undisturbed deep soil can be mineralized after the supply of fresh C by living plants to soil microbes. This result supports the idea that the SOM in deep soils is stable due to the energy-limitation of microbes and the ‘inert' pool of organic C defined in current models is not so ‘inert' finally. The supply of N in soil-plant system through the use of fertilizer or legume decreased the PE suggesting that the C storage in soils is limited by nutrient supply. Similarly, plant clipping reduced the plant N uptake thereby PE. Collectively these results suggest synchronization between plant N uptake and SOM mineralization supporting the idea that soils under permanent plant cover function as a bank of nutrients for the plant, maximizing plant productivity and nutrient retention. An innovative method clearly showed that the root exudation is the major way by which grassland plants induce PE. Moreover, saprophytic fungi are suggested as the key actors in the mineralization of recalcitrant SOM & PE. Lastly, we developed a new theory on temperature response of SOM mineralization by taking into account the energy-limitation of microbes and the temperature-dependent inactivation of enzymes. This theory predicts a negative relationship between temperature and mineralization of recalcitrant SOM, which was supported by experimental results. This finding challenges the classical paradigm of positive relationship between temperature and recalcitrant SOM mineralization. Overall, these investigations on plant-soil systems reinforce the idea that PE and underlying mechanisms play a key role in ecosystem C and N dynamics and even suggest that this role was underestimated in lab experiments.
7

Role of plant rhizosphere across multiple species, grassland management and temperature on microbial communities and long term soil organic matter dynamics

Shahzad, Tanvir 30 March 2012 (has links) (PDF)
It is increasingly being recognized that the soil microbes can mineralize recalcitrant soil organic matter (SOM) by using the fresh carbon (C) as a source of energy, a process called priming effect (PE). It has been shown mostly in lab incubations that PE can have important consequences for sequestration of organic C in soils. However, the importance of PE in C and N dynamics of ecosystems remains little known. The soil-plant interactions and rhizospheric processes can modulate the rates of PE and its consequences on C and N dynamics in an ecosystem. The objective of this thesis was to determine the role of PE in the C and N dynamics of permanent grasslands and the modulation of this role in response to management (plant clipping, fertilization) and global warming. Moreover, it was aimed to identify the microbial groups involved in PE and to unravel the way, e.g. absorption of N, root exudations and litter deposition, by which plant can induce PE. The thesis was based on a new approach allowing continuous dual labelling of multiple grassland plants with 13C- and 14C-CO2. The dual labelling permitted the separation of soil-derived CO2 from plant-derived CO2, the calculation of PE and the determination of mean age of soil-derived CO2-C. Moreover, phospholipids fatty-acids analysis (PLFA) permitted to correlate the variation of PE with changes in microbial community composition. Our work showed that the increased SOM mineralization under grasses was consistently two to three times more than that in bare soils (i.e. PE) over long term (511 days). This reveals that the PE plays key role in ecosystem CO2-C flux and indicates that a very large pool of SOM is under the control of PE. Moreover, we report that 15,000 years old organic C from an undisturbed deep soil can be mineralized after the supply of fresh C by living plants to soil microbes. This result supports the idea that the SOM in deep soils is stable due to the energy-limitation of microbes and the 'inert' pool of organic C defined in current models is not so 'inert' finally. The supply of N in soil-plant system through the use of fertilizer or legume decreased the PE suggesting that the C storage in soils is limited by nutrient supply. Similarly, plant clipping reduced the plant N uptake thereby PE. Collectively these results suggest synchronization between plant N uptake and SOM mineralization supporting the idea that soils under permanent plant cover function as a bank of nutrients for the plant, maximizing plant productivity and nutrient retention. An innovative method clearly showed that the root exudation is the major way by which grassland plants induce PE. Moreover, saprophytic fungi are suggested as the key actors in the mineralization of recalcitrant SOM & PE. Lastly, we developed a new theory on temperature response of SOM mineralization by taking into account the energy-limitation of microbes and the temperature-dependent inactivation of enzymes. This theory predicts a negative relationship between temperature and mineralization of recalcitrant SOM, which was supported by experimental results. This finding challenges the classical paradigm of positive relationship between temperature and recalcitrant SOM mineralization. Overall, these investigations on plant-soil systems reinforce the idea that PE and underlying mechanisms play a key role in ecosystem C and N dynamics and even suggest that this role was underestimated in lab experiments.
8

Neuroimaging markers in clinical trials for pre-dementia stages of Alzheimer's disease / Les marqueurs de neuroimagerie dans les études cliniques pour chaque étape des troubles précoces de la maladie d'Alzheimer

Cavedo, Enrica 08 December 2015 (has links)
Le développement de nouveaux médicaments, la validation et la standardisation des marqueurs de neuroimagerie et biochimie de la Maladie d'Alzheimer (MA) seront les principaux objectifs de la recherche de cette maladie dans les années à venir. La présente thèse vise à aborder ces questions cruciales. La première partie de la thèse fait le point sur l’application correcte des Procédures Opérationelles Standards (SOPs) pour l'acquisition de protocoles de neuroimagerie structurelle et l’application des marqueurs de neuroimagerie cérébrale dans 10 cliniques italiennes spécialisées dans les troubles de la mémoire. La deuxième partie traite de l'application de plusieurs marqueurs de neuroimagerie structurelle et fonctionnelle dans le cadre des études cliniques sur des patients ayant des troubles précoces de la maladie d'Alzheimer. Les résultats ont révélé que la mise en oeuvre des SOPs pour l’acquisition des séquences d’imagerie par résonance magnétique (IRM), au niveau multicentrique, réduit la variance des mesures des marqueurs de neuroimagerie détectée par différents scanners. En outre, les résultats de la deuxième partie de la thèse ont montré un impact significatif des thérapies anticholinestérasiques pour réduire l'atrophie de l'hippocampe, l'amincissement cortical ainsi que une augmentation de l'activation de zones du cerveau liées à l'IRM fonctionnelle chez des patients ayant des troubles précoces de la MA. Ces résultats prometteurs confirment l'hypothèse que les marqueurs de neuroimagerie structurelle et fonctionnelle appliqués avec SOPs pourraient être utilisés comme critère d'évaluation substitutif dans les études cliniques pour les patients ayant des troubles précoces de la maladie d'Alzheimer. / The development of new drugs and the validation and standardization of neuroimaging and biological markers for Alzheimer’s Disease (AD) clinical treatment trials is expected to be one of the major goals of AD research in the upcoming years. The present thesis aims to adress these critical issues. The first part of the thesis is focused on the proper application of Standard Operating Procedures (SOPs) for the structural neuroimaging protocols of acquisition and the implementation of neuroimaging markers in 10 Italian Memory Clinics. The second part of the thesis deals with the application of several structural and functional neuroimaging markers in the context of clinical trials investigation in mild cognitive impairment individuals. Results revealed that the implementation of SOPs at multicentre level reduces the variance of neuroimaging markers measurement detected by different scanners. Moreover, results from the employment of neuroimaging markers in pre-dementia trials in mild cognitive impairment individuals showed a significant impact of anticholinesterase therapies in reducing the hippocampal rate of atrophy, the cortical thinning as well as in increasing the activation of brain areas related to functional Magnetic Resonance Imaging (fMRI) face and location macthing tasks. These promising results support the hypothesis that structural and functional neuroimaging markers applied in a standardized manner migh be utilized as candidate surrogate outcomes in future pre-dementia trials for AD.
9

Esthétique et biodiversité des écosystèmes sous-marins / Aesthetics and biodiversity of marine ecosystems

Tribot, Anne-Sophie 27 November 2017 (has links)
La valeur esthétique des paysages et des espèces est un élément central de la conservation de la biodiversité, puisqu’elle fait intervenir les dimensions affectives et émotionnelles de notre rapport à la nature. Le lien entre biodiversité et perception esthétique demeure cependant peu étudié dans le cadre des services écosystémiques.Suite à un premier travail de synthèse ayant permis de poser les bases conceptuelles et méthodologiques de l’esthétique des paysages, trois études menées sur des systèmes sous-marins à différentes échelles ont permis de mieux comprendre et de quantifier le lien entre les différentes facettes de la biodiversité et la perception esthétique.Les résultats ont permis de mettre en évidence que la nature du lien entre biodiversité et préférences esthétique est dépendante de l’échelle de perception : à une échelle multi-spécifique, la biodiversité et la composition en espèces ont un effet positif sur les préférences esthétiques, tandis que les préférences à l’échelle spécifiques sont déconnectées du fonctionnement écologique des écosystèmes.Ces résultats confirment l’importance de la valeur esthétique dans notre perception de la biodiversité, qui pourrait avoir des conséquences majeures sur la façon dont nous protégeons notre environnement. L’approche fonctionnaliste de l’expérience esthétique est proposée et décrite afin de promouvoir une perception esthétique basée sur la compréhension et la reconnaissance des processus écologiques. Des pistes d’éducation à la biodiversité basée sur une expérience esthétique engagée sont également proposées afin de reconnecter les besoins écologiques et les préférences esthétiques. / The aesthetic value of landscapes and species is a central element for the conservation of biodiversity, since it involves the emotional and emotional dimensions of our relationship to nature. However, the links between biodiversity and aesthetic perception remains poorly studied and recognized within the ecosystem services framework.Following a first critical review, that described the conceptual and methodological bases of landscape aesthetics, three studies on underwater systems at different scales have been computed in order to better understand the link between the different facets of biodiversity and aesthetic perception.The results revealed that the link between biodiversity and aesthetic preferences is dependent on the scale of perception: at a multi-specific scale, biodiversity and species composition have a positive effect on aesthetic preferences, while preferences at a specific scale are disconnected to the ecological functioning of ecosystems.These results confirm the importance of aesthetic value in our perception of biodiversity, which could have major consequences in the way we protect our environment. The aesthetic experience based on the understanding of ecological functioning is proposed and described in order to promote an aesthetic perception relevant to ecological processes. Education to biodiversity based on engaged aesthetic is also proposed, in order to reconnect ecological needs and aesthetic preferences.
10

Structural and functional characterisation of the CCR4- NOT deadenylation complex / Caractérisation fonctionnelle et structurale du complexe de déadénylation CCR4-NOT

Roudko, Vladimir 19 September 2014 (has links)
La dégradation des ARN messagers (ARNm) est un processus universel extrêmement complexe. D’une manière semblable aux polymerases pour la transcription et ribosomes pour la traduction, les complexes de protéines effectuant la dégradation des ARNm sont précisément régulés. La dégradation des ARNm eucaryotes s’effectue selon un schéma conservé évolutivement qui est initié par la déadénylation résultant dans la formation de transcrits avec des queues polyA courtes. De tels intermédiaires sont alors dégradés par le clivage de leur coiffe suivi par une digestion exonucléolytique 5’-3’ effectuée par Xrn1, ou alternativement par une digestion 3 ’-5’ catalysée par l’exosome. Dans ma thèse je présente une dissection fonctionnelle du complexe de déadénylation CCR4-NOT basée sur son analyse structurale. Je me suis essentiellement intéressé à cinq questions fondamentales concernant ce complexe : La formation du complexe CCR4-NOT complexe est-elle requise pour la déadénylation ? Quel est le rôle moléculaire de sous-unités Not2/3/5 du complexe ? Pourquoi la protéine Not1 est-elle essentielle chez la levure ? Le complexe CCR4-NOT joue-t-il un rôle dans la répression de la traduction ? Comment le complexe CCR4-NOT est-il ciblé sur ses substrats ARNm ? / MRNA degradation is a highly complex and versatile process. In a manner similar to polymerase complexes in transcription and ribosomes in translation, protein complexes mediating mRNA decay are tightly regulated. Eukaryotic mRNA decay follows a conserved pathway initiated by deadenylation that generates transcripts with short polyA tails. The latter intermediates are degraded either by decapping followed with 5’-3’ trimming mediated by Xrn1, or by exosome-mediated digestion in the 3’-5’ direction. In my thesis I present a functional dissection of the Ccr4-Not deadenylase complex based on its structural analysis. Essentially, I addressed five fundamental questions related to this complex: Is CCR4-NOT complex formation required for deadenylation activity? What is the molecular role of associated Not2/3/5 subunits? Why is the Not1 protein essential in yeast? Does the CCR4-NOT complex play role in translation regulation? How is the CCR4-NOT complex targeted to its mRNA substrates?

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