Дисертації з теми "Rôle nucléaire"
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Claudel, Thierry. "Rôle du récepteur nucléaire FXR dans le métabolisme lipidique." Lille 2, 2003. http://www.theses.fr/2003LIL2P005.
Tertrais, Bruno. "La stratégie nucléaire de l'OTAN : dissuasion élargie et rôle des armes nucléaires américaines en Europe, 1949-1992." Paris, Institut d'études politiques, 1994. http://www.theses.fr/1994IEPP0037.
This study offers a comprehensive perspective on the operational aspects of NATO's nuclear strategy, through an analysis of the role of us nuclear weapons in Europe from 1949 to 1992. Preliminary questions concern : the way NATO's strategy has been constructed ; the nature of this strategy ; and the structure of its historical evolution. Part I, "looking for a common doctrine : the dilemmas of extended deterrence", describes the emergence of the concept of tactical use of nuclear weapons, and the difficulties encountered in the alliance to implement a strategy based on a massive recourse to nuclear weapons. Part II, "a solution to the dilemmas ? Flexible response as a modus operandi for extended deterrence" analyses the compromises on which flexible response is based, the way this strategy has been implemented, and the subsequent modifications in NATO's nuclear posture. Part III, "challenge to extended deterrence : NATO's nuclear strategy and the end of the cold war", analyses the consequences of the political upheavals in Europe for NATO's nuclear strategy, and questions the validity of this strategy. In conclusion, the author suggests, in particular, that political will has played a key role in ensuring that NATO's nuclear strategy develops in a coherent fashion. A critical analysis of NATO's nuclear strategy is also included
Fontaine, Coralie. "Rôle et régulation du récepteur nucléaire orphelin REV-ERB α : voies d'interaction avec les récepteurs nucléaires PPARγ et LXR". Lille 2, 2006. http://www.theses.fr/2006LIL2S012.
Nuclear receptors (NR) function as ligand-dependent transcription factors that bind DNA and transduce physiological signals into gene regulation. Nucler receptors regulate gene expression involved in reproduction, development and metabolism. Recent genetic, pharmalogical and biochemical studies on members of the nuclear receptor superfamily (e. G. " Peroxisome Proliferator-Activated Receptors " (PPAR), " Liver X Receptors " (LXR)) have uncovered new signaling pathways that regulate metabolism, and provided new insights into the pathophysiology of diabetes, dyslipidemia, obesity, vascular inflammation. In addition to the ligand-activated Nrs, many members within this superfamily have no ligand, and are referred to as " orphan nuclear receptors ". Rev-erbα (NR1D1) is an orphan member of the steroid/thyroid hormone receptor nuclear family, which acts as a repressor of genes transcription. The aim of this study was to investigate a possible cross-talk between these nuclear receptors. First, we identified Rev-erbα as a new target gene for PPARγ in the adipogenic cascade of transcription factors and as an important factor modulating adipocyte function, at least in part, by enhancing the adipogenic action of PPARγ. In a second part of this work, we find that LXR activation by synthetic agonists induces Rev-erbα mRNA expression in human primary macro^phages. In addition, the results reported here show that Rev-erbα acts as negative regulator of LXR transactivation, on a new LXR target gene, the LPS receptor, TLR-4. Interestingly, LXR and Rev-erbα bind to the same response element on the TLR-4 promoter. As such, Rev-erbα inhibits transcriptional activation mediated by nuclear receptors, which directly regulate Rev-erbα expression. To conclude, Rev-erbα appears to drive transcriptional feedback loops of many nuclear receptors controlling physiological processes. Thus, the Rev-erbα regulation pathway may converge to integrate metabolism, inflammation and circadian cycle conferring physiological flexibility
Boukhtouche, Fatiha. "Rôle du récepteur nucléaire RORα dans la survie et la différenciationneuronale". Phd thesis, Université Pierre et Marie Curie - Paris VI, 2006. http://tel.archives-ouvertes.fr/tel-00080417.
dont la perte de fonction entraîne chez la souris staggerer - entre autres phénotypes - une
sévère ataxie cérébelleuse. RORα a longtemps été considéré comme un récepteur nucléaire
orphelin, cependant, le cholestérol (ou un de ses dérivés) semble être un ligand physiologique
de ce récepteur.
Le mutant staggerer, identifié dès 1962 par Sidman, Lane et Dickie, présente une
hypoplasie cérébelleuse liée à l'absence de la grande majorité des cellules de Purkinje, ainsi
que des grains du cervelet. L'expression de la mutation staggerer dans les cellules de Purkinje
conduit à leur mort massive pendant le développement, et les cellules de Purkinje survivantes
chez l'adulte présentent d'importantes anomalies de différenciation. Par ailleurs, à l'état
hétérozygote, le mutant staggerer présente une diminution de la survie des cellules de
Purkinje ainsi que des anomalies de différenciation au cours du vieillissement.
Le phénotype cérébelleux des mutants homozygote et hétérozygote staggerer
suggère que RORα est impliqué dans la survie et/ou la différenciation des cellules de Purkinje
au cours du développement et du vieillissement. Au cours de cette thèse, nous avons donc
tenté de déterminer le rôle de RORα dans la survie et la différenciation dans des neurones
corticaux et/ou dans des cellules de Purkinje, en étudiant l'effet de sa surexpression dans ces
processus.
Afin de surexprimer RORα, nous avons construit un vecteur lentiviral exprimant
l'isoforme humaine RORα1. Ce vecteur nous a permis de transduire avec une très grande
efficacité des neurones corticaux en culture primaire ainsi que les cellules de Purkinje en
culture organotypique.
Dans une première étude, nous avons cherché à déterminer si RORα pouvait exercer
un rôle dans la survie neuronale. Dans ce but, nous avons évalué la survie de neurones
corticaux surexprimant ou non RORα et soumis à un stress oxydatif entraînant l'apoptose des
neurones. RORα protège les neurones en diminuant le stress oxydatif causé par ces inducteurs
pro-apoptotiques. L'expression des deux enzymes Glutathion peroxydase 1 et Peroxiredoxine
6 est augmentée dans les neurones qui surexpriment hRORα1, et semble partiellement médier
l'effet neuroprotecteur de RORα. Nous avons par ailleurs évalué et comparé la survie des
cellules de Purkinje en culture organotypique qui expriment RORα de façon endogène, ou qui
surexpriment hRORα1, et nos résultats suggèrent que la surexpression de RORα a également
un effet neuroprotecteur dans ces cellules.
Dans une seconde étude, afin de déterminer le rôle de RORα dans la différenciation
des cellules de Purkinje, nous avons analysé en culture la progression de la différenciation
dendritique précoce de cellules de Purkinje en fonction de l'expression de RORα. RORα est
crucial pour l'étape de régression des neurites des cellules de Purkinje au stade bipolaire
embryonnaire. Alors que l'absence de RORα chez les mutants homozygotes staggerer
entraîne un arrêt de la différenciation des cellules de Purkinje à ce stade (les cellules de
Purkinje ne parviennent pas à entamer la régression des neurites), la surexpression de
hRORα1 accélère l'étape de régression. Cette étape de régression est totalement dépendantede l'expression de protéines RORα fonctionnelles et cet effet est vraisemblablementintrinsèque. Nous montrons enfin que l'hormone thyroïdienne accélère la différenciationdendritique précoce des cellules de Purkinje, et que RORα semble contribuer à ce processus.
L'ensemble de ces résultats montre que RORα intervient de façon cruciale à la foisdans la survie et dans la différenciation des cellules de Purkinje dans une étape très précoce de
leur développement post-natal.
Therizols, Pierre. "Rôle de la périphérie nucléaire dans l'organisation spatiale et fonctionnelle des subtélomères chez Saccharomyces cerevisiae." Paris 6, 2008. http://www.theses.fr/2008PA066371.
Dijon, Aurore. "Evolution de la collectivité autour du 68Ni : rôle des états intrus." Phd thesis, Université de Caen, 2012. http://tel.archives-ouvertes.fr/tel-00728430.
Berthélemy, Michel. "L'économie de l'énergie nucléaire : quatre essais sur le rôle de l'innovation et de l'organisation industrielle." Phd thesis, Ecole Nationale Supérieure des Mines de Paris, 2013. http://pastel.archives-ouvertes.fr/pastel-00875147.
Boukhtouche, Fatiha. "Rôle du récepteur nucléaire RORα dans la survie et la différentiation des neurones". Paris 6, 2006. http://www.theses.fr/2006PA066007.
Vitaliano-Prunier, Adeline. "Rôle de l'ubiquitination dans le couplage entre biogénèse et export nucléaire des ARNm." Paris 6, 2010. http://www.theses.fr/2010PA066250.
Aureille, Julien. "Mécanotransduction au cours du cycle cellulaire : Rôle de la déformation de l'enveloppe nucléaire." Thesis, Université Grenoble Alpes (ComUE), 2018. http://www.theses.fr/2018GREAV072/document.
.The shape of the cell nucleus can vary considerably during developmental and pathological processes as a consequence of the mechanical forces emanating from the microenvironment or generated by the cytoskeleton. However the impact of nuclear morphology on the transcriptional machinery is not known. Using a combination of tools to manipulate the nuclear morphology, we observed that changes in nuclear shape regulate the activity of AP1 and TEAD. We showed that nuclear flattening increases c-Jun phosphorylation and YAP nuclear translocation, leading to transcriptional induction of AP1 and TEAD-target genes. Surprisingly, we found that nuclear compression is necessary and sufficient to mediate c-Jun and YAP activation in response to cell- generated contractility or cell spreading. We additionally observed that nuclear flattening occurs during the cell cycle and promotes proliferation via TEAD and AP1- dependent G1 to S progression
Leveque, Hervé. "Le rôle de l'électricité d'origine nucléaire dans le tiers monde : le cas de l'Algérie et de l'Indonésie." Paris 9, 1987. https://portail.bu.dauphine.fr/fileviewer/index.php?doc=1987PA090054.
Proceeding from long term studies on energy beginning in earlier seventies, the potentiality of nuclear power in third world will be restricted to two regions: arabian world and south east asia. Two countries of our choice, Algeria and Indonesia, pointing out of our two geographical areas, will reach by macroeconomic and financial analysis a better understanding of the stake of nuclear energy
Ducoin, C. "Rôle de l'isospin dans la transition de phase liquide-gaz de la matière nucléaire." Phd thesis, Université de Caen, 2006. http://tel.archives-ouvertes.fr/tel-00110371.
La transition liquide-gaz nucléaire est associée au phénomène de multi-fragmentation observé dans les collisions d'ions lourds, ainsi qu'à la physique des étoiles compactes : les systèmes concernés sont riches en neutrons, donc affectés par le degré de liberté d'isospin.
Le travail présenté ici est une étude théorique des effets d'isospin apparaissant dans la transition liquide-gaz de la matière nucléaire asymétrique. Une approche de champ moyen est employée, avec une interaction nucléaire effective de type Skyrme. Nous démontrons la présence d'une transition du premier ordre pour la matière asymétrique, et étudions le phénomène de distillation d'isospin qui l'accompagne. Le cas d'une séparation de phase à l'équilibre thermodynamique est comparé à celui d'une décomposition spinodale. Les effets de taille finie sont abordés, ainsi que l'influence du gaz d'électrons présent dans le contexte astrophysique.
Dugardin, Camille. "Rôle du récepteur nucléaire Rev-erbα dans le contrôle du métabolisme lipidique dans l'entérocyte". Thesis, Lille 2, 2016. http://www.theses.fr/2016LIL2S045.
The intestine plays a key role in the control of energy homeostasis. Enterocytes, which constitute the main cellular type of intestinal epithelium (> 90%), are polarized cells allowing exchanges between intestinal lumen (apical membrane) and lymph/blood compartment (basolateral membrane). In this thesis, cholesterol and lipid metabolism control by enterocytes was studied and particularly, trans intestinal cholesterol excretion (TICE) and dietary lipid absorption.Recently, it has been estimated that intestine contributes 20-30% of fecal neutral sterol excretion in chow-fed mice. This pathway called TICE involves the direct luminal secretion of plasma-derived cholesterol by enterocytes. Moreover, TICE can be pharmacologically modulated, for instance by ezetimibe and statins and so, represents a new therapeutic target in order to prevent atherosclerosis in type 2 diabetic patients. However, at present, the molecular mechanisms behind the trans-enterocytic process of TICE are still unknown, especially the steps sustaining cholesterol entry, trafficking and efflux in enterocytes. In the first study of this thesis, we highlighted the human enterocytic Caco-2/TC7 cell line as a suitable model to study the enterocyte-related processes of TICE. We have first shown that upon basolateral incubation with human plasma and apical incubation with lipid micelles, differentiated Caco-2/TC7 cells mimic some of the in vivo TICE features. Moreover, using this model, we have identified a key role of the microtubule network in the process.In the second study of this thesis, chylomicron secretion by enterocytes and its control by the nuclear receptor Rev-erbα were investigated. Indeed, although chylomicron remnant accumulation has been associated to a delayed clearance by the liver, some recent studies show that chylomicron overproduction by the intestine is a major contributor to dyslipidemia in insulin resistant patients. Dietary lipid absorption results from a balance between transient storage in enterocytes as cytosolic lipid droplets (LD) and secretion as triglyceride-rich lipoproteins (TRL). The nuclear receptor Rev-erbα is a transcriptional repressor involved in the energy metabolism and the circadian rhythm. Particularly, Rev-erbα controls lipid metabolism in the liver and thus the catabolism of TRL. The aim of this second study was to investigate the role of Rev-erbα in intestinal lipid metabolism and particularly in TRL secretion. To study that, Caco-2/TC7 cells infected with lentivirus encoding or not a shRNA targeting Rev-erbα (sh Rev-erbα) were grown on transwells. Compared to sh control, sh Rev-erbα Caco-2/TC7 cells secrete higher amounts of micelle-derived LRT in the basolateral medium and exhibit lower quantity of neutral lipids stored as cytosolic LD, whereas the apical uptake is not different. Activation of lipophagy in sh Rev-erbα compared to sh control cells was evidenced by a higher autophagic flux and an increased colocalization of the autophagy marker LC3 with LD. Finally, autophagy inhibition with bafilomycin in sh Rev-erbα cells restores lipid secretion to the same level as in sh control cells. This second study show that Rev-erbα knock-down in enterocytes leads to a higher lipophagy-mediated remobilization of intracellular lipids and an increased TRL secretion. Our hypothesis is that Rev-erbα may be a molecular gear in the control of chylomicron secretion and a major regulator of post-prandial triglyceridemia.In conclusion, these two studies allow to better understand lipid metabolism control by the intestine: the first one by identifying the contribution of the microtubule network in enterocytes for trans-enterocytic retrograde cholesterol transport; the second one by highlighting the nuclear receptor Rev-erbα as a regulator of TRL secretion by enterocytes. These two studies point out the intestine as a potential therapeutic target to treat dyslipidemia in type 2 diabetic patients
Ducoin, Camille. "Rôle de l'isospin dans la transition de phase liquide-gaz de la matière nucléaire." Caen, 2006. http://www.theses.fr/2006CAEN2028.
Nuclear matter presents a phase transition of the liquid-gas type. This well-known feature is due to the nuclear interaction profile (mean-range attractive, short-range repulsive). Symmetric nuclear matter thermodynamics is thus analogous to that of a Van der Waals fluid. The study shows up to be more complex in the case of asymmetric matter, composed of neutrons and protons in an arbitrary proportion. Isospin, which distinguishes both constituents, gives a measure of this proportion. Studying asymmetric matter, isospin is an additional degree of freedom, which means one more dimension to consider in the space of observables. The nuclear liquid-gas transition is associated with the multi-fragmentation phenomenon observed in heavy-ion collisions, and to compact-star physics : the involved systems are neutron rich, so they are affected by the isospin degree of freedom. The present work is a theoretical study of isospin effects which appear in the asymmetric-nuclear-matter liquid-gas phase transition. A mean-field approach is used, with a Skyrme nuclear effective interaction. We demonstrate the presence of a first-order phase transition for asymmetric matter, and study the isospin distillation phenomenon associated with this transition. The case of phase separation at thermodynamic equilibrium is compared to spinodal decomposition. Finite size effects are addressed, as well as the influence of the electron gas which is present in the astrophysical context
Rieusset, Jennifer. "Rôle du récepteur nucléaire PPARγ dans l'action de l'insuline dans le tissu adipeux humain". Lyon 1, 1999. http://www.theses.fr/1999LYO1T245.
Martinot, Emmanuelle. "Etude du rôle du récepteur nucléaire FXRα dans la physiologie et la physiopathologie testiculaire". Thesis, Clermont-Ferrand 2, 2015. http://www.theses.fr/2015CLF22644/document.
Fxrα is the bile acid nuclear receptor, predominantly expressed in liver, intestine, kidney and adrenal glands. In recent years, interest in Fxrα has been increasing due to its central role in the control of cholesterol, bile acids, triglycerides or glucose homeostasis. More recently, Fxrα and its ligands, bile acids, have been detected in the testis pointing out its potential involvement in this tissue and more widely in the male reproductive functions. However, the few studies on this topic focused essentially on Fxrα involvement in the control of steroids metabolism. Indeed, activation of Fxrα in vivo with a synthetic agonist leads to short-term steroidogenesis repression in the adult. In vivo the impact of alteration of Fxrα signaling on the global testis physiology has never been explored so far. Such studies would be pertinent considering that Fxrα is a target for the treatment of metabolic diseases such as dyslipidemia or diabetes. In this context, the aim of my work was to study the implication of Fxrα in testis physiology and physiopathology by analyzing a knock out mouse model for Fxrα. Our results show that: 1) the loss of Fxrα increase germ cell mortality in the testis in a disease context of cholestasis ; 2) over-activation of Fxrα signaling during puberty leads to germ cell differentiation defects, associated with an alteration of testis endocrine function ; 3) besides steroidogenesis control in Leydig cell, Fxrα is involved in Sertoli cell functions and spermatogonial stem cell proliferation and/or differentiation. Taken together, these data define Fxrα as a new actor involved in the control of testis physiology, and should be taken into consideration regarding the use of Fxrα agonistic or antagonistic ligands for the treatment of metabolic diseases
Cohen, Gérard. "Théorie de la décision, décision et non-decision dans l'électronucléaire : le rôle du décideur." Reims, 2005. http://theses.univ-reims.fr/exl-doc/GED00000311.pdf.
The electro-nuclear industry is a minefield for decision makers. The problem has migrated from the economic to the political sphere, a phenomenon which the latter would rather have avoided. . . How and why? The first part of this thesis presents a diagnostic of the formal decision making system in the electro-nuclear field. It is clear that this system is structurally inefficient. The second part explores the true decision making system in the electro-nuclear field, revealing the existence of an underlying, virtually secret decision making system, unique to this industry. This is explained (particularly with a diagram) and proved twice by the facts. The conclusion is also very clear : in the electro-nuclear industry, everyone knows what must (inevitably ) be done, but no one will make any decisions! Quid about a theory in this case ? The third part investigates precisely how academic thought might explain the situation. The conclusion is, again, clear : no theory can satisfactorily explain exactly what is observed. The conclusion of this study proposes defining the electro-nuclear field as a “meta problem” or a “meta organization“. It shows how this particular definition can better explain what is happening in this field, essentially by means of six new diagrams, which, juxtaposed with the first one, can serve as a graphic summary of it
Potvin, Catherine. "Rôle du récepteur nucléaire de la progestérone dans la ventilation chez des souris en développement." Thesis, Université Laval, 2014. http://www.theses.ulaval.ca/2014/30709/30709.pdf.
Delezie, Julien. "Rôle du récepteur nucléaire Rev-erba dans les mécanismes d'anticipation des repas et le métabolisme." Phd thesis, Université de Strasbourg, 2012. http://tel.archives-ouvertes.fr/tel-00801656.
Abdelkarim, Mouaadh. "Rôle du récepteur nucléaire Farnesoid X : receptor (FXR) dans la différenciation et la fonction adipocytaire." Lille 2, 2010. http://www.theses.fr/2010LIL2S005.
Lü, Hongliang. "Synthèse des noyaux super-lourds : rôle de l'analyse d'incertitudes dans la modélisation." Caen, 2015. http://hal.in2p3.fr/tel-01235448.
The existence of super-heavy elements (SHE) has been predicted by the nuclear shell model. However, the nuclear reaction theory for heavy systems has not been well established yet. Large discrepancies between quantitative predictions still persist because of the presence of the fusion hindrance phenomenon. The first aim of this PhD work is to investigate different models associated with the complete description of the fusion-evaporation reaction. Then, a complete uncertainty analysis, in combination with a newly-developed cascade code called KEWPIE2, is performed. By inspecting uncertainties due to parameters and models, it is clearly revealed that the fission barrier has the most crucial role to play in constraining the fusion models. How to determine the uncertainty associated with the fission barrier? Since we do not have enough reliable data, we propose to consider Bayesian inference by reversing the usual mode of thinking. Based upon the KEWPIE2 code with simulated pseudo-data, preliminary results tell us that the estimated uncertainty in the fission barrier appears to be quite sensitive to the number and precision of data points as well as the nuisance parameters. Furthermore, it is known that the fusion process and the fission barrier can be both described within the framework of the liquid-drop model. Thus, they should be correlated with each other. With the help of a simple liquid-drop mass formula and the regression theory, uncertainties in the model parameters as well as the correlation between the neutron-separation energy and fission barrier are inspected. The influence of their covariances on the survival probability is concretely investigated
Jolly, Sarah. "Etude du rôle du récepteur nucléaire RORalpha dans les neurones et les astrocytes lors d'une hypoxie." Paris 6, 2011. http://www.theses.fr/2011PA066718.
Bouhlel, Mohamed Amine. "Rôle du récepteur nucléaire PPARγ dans les macrophages alternatifs humains : de l'inflammation à l'homéostasie du cholestérol". Lille 2, 2007. http://www.theses.fr/2007LIL2S030.
Noizet, Alain. "Le rôle cognitif des activités routinières : le cas des interventions de terrain familières en centrale nucléaire." Paris 8, 2000. http://www.theses.fr/2000PA081810.
Sojka, Jaroslav. "Fragilisation par l'hydrogène d'aciers faiblement alliés, utilisés dans l'industrie nucléaire : rôle de la microstructure et de l'état inclusionnaire." Châtenay-Malabry, Ecole centrale de Paris, 1997. http://www.theses.fr/1997ECAP0538.
Cherbonnier, Claire. "Potentialisation de l'apoptose de cellules tumorales par des facteurs de croissance : rôle du facteur nucléaire NF-kB." Paris 11, 2003. http://www.theses.fr/2003PA11TO19.
Roure, Virginie. "Rôle des protéines du groupe Polycomb et trithorax dans l'organisation nucléaire des gènes homéotiques chez Drosophila melanogaster." Montpellier 1, 2008. http://www.theses.fr/2008MON1T047.
Toussaint, Jean-François. "Rôle de la résonance magnétique nucléaire dans la caractérisation tissulaire de l'athérosclérose et l'évaluation de la rupture de plaque." Paris 5, 1995. http://www.theses.fr/1995PA05CD12.
In 1995 atherosclerosis still remains the first cause of mortality ans morbidity in developed countries. However, we cannot yet predict the evolution of its histopathological substratum, the atheromatous plaque, for the morphological parameters available from angiography do not provide this information. A biochemical imaging technology is now necessary to improve our understanding of the in vivo mechanisms of plaque rupture leading to arterial ischemia and infarction. With this goal we have used Magnetic Resonance to realize a non-invasive tissue characterization of atheromatous lesions. Using carbon-13 MR spectroscopy, proton spectroscopy, diffusion imaging, T1 contrast, psin density, and especially T2 contrast imaging, we have demonstrated that Magnetic Resonance allows to study atherosclerosis progression by analyzing fatty acid and cholesteryl ester content, and to investigate plaque stability by discriminating soft lipid regions (atheroma) from fibrous structures (sclerosis). We have also proven that MR can discriminate thesqe components in vivo, which provides a new and powerful way to study regression or stabilization of this dresdful disease
Ohayon, Delphine. "Rôle de PCNA cytoplasmique dans la survie cellulaire." Thesis, Sorbonne Paris Cité, 2016. http://www.theses.fr/2016USPCC324.
Cytosolic proliferating cell nuclear antigen (PCNA), a scaffolding protein involved in DNI replication, has been described as a key element in survival of neutrophil, a non-proliferating cell. Without enzymatic activity this main function is to build a protein scaffold through the binding and functional coordination of its different partners. This relocation of PCNA from the nucleus into the cytoplasm occurs at the end of granulocytic differentiation. From our present findings, we propose new paradigm in which cytosolic PCNA builds a protein scaffold that dictates Acute Myeloid Leukemia (AML) cell survival by enhancing their glycolytic metabolism and in turn conferrinl chemotherapy resistance. We have demonstrated that daunorubicin-resistant HL-60 cells (HL-60R have a prominent cytosolic PCNA localization due to increased nuclear export compared to their sensitive counterpart. By interacting with nicotinamide phosphoribosyltransferase (NAMPT), protein involved in the NAD biosynthesis, PCNA coordinates the glycolysis pathway and survival especially in HL-60R cells.In neutrophil, we have also demonstrated a functional and structural interaction between a protein p47Phox: a cytosolic subunit of NADPH oxidase and PCNA which suggested that PCNA control the survival and maintain the resting state of neutrophils. PCNA is a key element involved in survival of different types of cells. Decipher the molecular mechanisms of PCNA to modulate its partners represent a promising avenue of research
Pourcet, Benoit. "Mécanismes moléculaires de la régulation du récepteur nucléaire humain PPAR alpha : un rôle clef des modifications post-traductionnelles." Lille 2, 2009. http://www.theses.fr/2009LIL2S007.
Magnier, Benjamin. "Rôle du récepteur nucléaire Liver Receptor Homolog-1 (LRH-1) dans l’homéostasie du cholestérol et des acides biliaires." Université Louis Pasteur (Strasbourg) (1971-2008), 2007. https://publication-theses.unistra.fr/restreint/theses_doctorat/2007/MAGNIER_Benjamin_2007.pdf.
The goal of this work was to evaluate the in vivo role of the nuclear receptor Liver receptor homolog 1 (LRH-1) in the control of cholesterol and bile acid homeostasis. To this end, a mouse model in which the LRH-1 gene is specifically deleted in the hepatocytes was generated. These mice show a massive reduction of CYP8B1 and fail to produce cholic acid. In addition, we also show that the profound remodeling of the BA composition reduces significantly the efficacy of intestinal absorption of lipids and re-uptake of BAs and facilitates the removal of lipids from the body. Our studies hence unequivocally demonstrate a pivotal role for LRH-1 in determining the composition of BAs, which, in turn, has major consequences on the whole body lipid homeostasis. The second step of this work was to study the impact of the absence of LRH-1 on the hepatic transcriptome. The preliminary outcome of this study is suggestive for a predominant role of LRH-1 in both lipid metabolism and immune defense
Le, May Cédric. "Rôle du récepteur nucléaire PPAR alpha dans la régulation du métabolisme énergétique hépatique et l'effet transcriptionnel des acides gras." Paris 7, 2004. http://www.theses.fr/2004PA077111.
Meng, Pinghong. "Rôle du métabolisme de l'Inositol dans le contrôle de la prolifération et de la mort cellulaire." Paris 11, 2008. http://www.theses.fr/2008PA112229.
Terzian, Tamar. "Créatine kinase-BB (CK-BB) : spécificités izoenzymatiques, localisation nucléaire et rôle dans la croissance des cellules tumorales MCF-7." Lyon 1, 2000. http://www.theses.fr/2000LYO1T106.
Clouet, Christelle. "Rôle de HR39 récepteur nucléaire aux stéroïdes dans le développement des corps pédonculés et la mémoire de Drosophila melanogaster." Montpellier 2, 2006. http://www.theses.fr/2006MON20146.
Célerier, Christophe. "Rôle d'un pharmacien dans le domaine des radiopharmaceutiques : expérience du service de Médecine Nucléaire de l'hôpital du Haut-Lévêque." Bordeaux 2, 1995. http://www.theses.fr/1995BOR2P085.
Gingras, Luc. "Le rôle de l'asymétrie de masse et de l'asymétrie d'isospin en voie d'entrée pour la production de particules et de fragments dans les collisions d'ions lourds." Doctoral thesis, Université Laval, 2002. http://hdl.handle.net/20.500.11794/35029.
Québec Université Laval, Bibliothèque 2019
Cigna, Natacha Marie Laure. "Etude du rôle du facteur de transcription Microphthalmia (Mitf) dans la différenciation de la rétine." Paris 11, 2008. http://www.theses.fr/2008PA112145.
Eye development requires a set of secreted factors driving the combined expression of specific transcription factors which ultimately lead to differentiation. The BHLH-LZ transcription factor Mitf is involved in pigmented cell differentiation (retinal pigmented epithelium (EPR) and neural crest cell derived melanocyte. Mitf encodes several isoforms whose expression from tissue-specific promoter lead to differences in their N-terminal-ends. The A form is mainly expressed in EPR whereas the M form is specifically detected in melanocytes. In this study we contributed to show evidence of a nuclear export signal (NES) within Mitf. Located in the comon C-terminal end of these isoforms (just after the leucine zipper), this CRM1-dependent NES seems to be used in a differential way. Thus, Mitf-A is found both in the nucleus and the cytoplasm whereas Mitf-M is only detected in the nucleus. This export of Mitf is controlled in part by the kinase GSK3-β through the phosphorylation of a specific serine (S399 for Mitf-A and S298 for Mitf-M) which causes an accumulation of Mitf in the cytoplasm. We also adress the relationship between Mitf and the Shh signaling pathway. We showed evidence for a role of Mitf and Shh in the induction of the pigmentation. In primary cultured neuroretina cells , the co-transfection of these two genes caused an epithelialization of the pigmented foci icobime to an increase of their number and the diminution of their size, indicating a combine effect of these Shh and Mitf in the proliferation. This interaction may take place by a transcriptionnal modulation of Shh expression by Mitf through a reponse element called M box. This control would be isoform dependent. Moreover, the spatio-temporal expression of Mitf and Shh in chicken eye development seems to be the same indicating that this process could occur in vivo
Sberna, Anne-Laure. "Etude du rôle du récepteur nucléaire CAR, Constitutive Androstane Receptor, dans le métabolisme des lipides et la susceptibilité à l'athérosclérose." Phd thesis, Université de Bourgogne, 2011. http://tel.archives-ouvertes.fr/tel-00825474.
Filhol-Cochet, Odile. "Translocation nucléaire de la caséine kinase II : rôle possible dans le contrôle de la transcription et de la prolifération cellulaire." Grenoble 1, 1990. http://www.theses.fr/1990GRE10029.
Fradet, Anaïs. "Rôle du récepteur nucléaire orphelin ERRalpha dans le développement des métastases osseuses du cancer du sein et de la prostate." Thesis, Lyon 1, 2012. http://www.theses.fr/2012LYO10308.
Breast cancer and prostate cancer patients, often developed bone metastases. As ERRalpha, an orphan nuclear receptor, is involved in bone physiology and is considered as a bad prognosis factor in breast and prostate cancer, we hypothesize that it can be implicated in bone metastasis development that derived from breast and prostate cancers. While we found that, in both cases, ERRalpha stimulates the development of the primary tumor through regulation of angiogenesis and VEGF expression, we show that ERRalpha inhibits osteolytic lesions from breast cancer cells via the regulation of osteoclastogenesis and OPG expression. On the other side ERRalpha stimulates osteolytic lesions from prostate cancer through regulation of TGFbeta, MCP-1 and cathepsin K expression while inducing new bone formation combine with OPG, endothelin-1, and Wnts regulation. All together, our results confirmed ERRalpha as a bad prognosis factor in breast and prostate primary tumors. They also show a dual function of ERRalpha in bone metastasis development as an inhibitor and a stimulator of bone metastasis derived from breast and prostate cancer respectively which suggest different ERRalpha mechanisms that may depend of cancer cells but also of the microenvironment and hormonal status
Boulinguiez, Alexis. "Rôle du récepteur nucléaire Rev-erb-α dans la fonction du réticulum sarcoplasmique du muscle squelettique : implications physiologiques et pathologiques". Thesis, Lille, 2019. http://www.theses.fr/2019LIL2S004.
Within skeletal muscle, the sarcoplasmic reticulum plays an essential role in the regulation of calcium homeostasis and muscle contraction. In particular, the SERCA transporter, located at the membrane of the endoplasmic reticulum, by pumping calcium from cytosol from reticular lumen, allows the reticular calcium content to be reconstituted following muscle contraction. In skeletal muscle, SERCA activity is controlled by a specific inhibitory peptide called myoregulin. We are interested in the role of the nuclear receptor Rev-erb-α, a transcription repressor known to promote muscle function and whose activity can be modulated by pharmacological ligands. Our results show that Rev-erb-α represses the expression of myoregulin by binding to its promoter, which results in an increase in SERCA activity and an increase in reticular calcium content. Treatment with a Rev-erb-α agonist, SR9009, improves calcium homeostasis and muscle contractility in mdx/utr+/- mice, a model of Duchenne myopathy. In addition, the endoplasmic reticulum is the site of protein conformation of the secretory pathway. Alteration in protein conformation causes reticular stress and triggers the unfolded protein response that can lead to apoptosis. It is described that reticular stress is a phenomenon involved in the activation of skeletal muscle satellite cell following an injury. We have established that Rev-erb-α, by increasing the interaction between endoplasmic reticulum and mitochondria enhances the activation of unfolded protein response and apoptosis of activated satellite cells, which could impact the muscle regeneration capacity. In conclusion, we have identified Rev-erb-α as a modulator of endoplasmic reticulum function in skeletal muscle. In the future, specific Rev-erb-α targeting therapies may be developed for human muscle diseases
Pierre, Virginie. "L'acrosome du spermatozoïde de sa biogenèse à son rôle physiologique." Thesis, Grenoble, 2013. http://www.theses.fr/2013GRENS035/document.
The spermatozoon is a highly specialized cell that must be able to perform specific functions tofertilize the oocyte. It must be able to perform the acrosome reaction, an exocytosis of a giant vesicleof secretion, attached to the nucleus. This vesicle contains enzymes that allow the sperm to penetratethe zona pellucida surrounding the oocyte. The aim of my work was first to study the effect of anenzyme present in the acrosome, the sPLA2 of group X in mouse (mGX). This is the onlymammalian phospholipase among the five tested that has an inhibitory effect on sperm specificpopulation with low mobility. My work has confirmed the specificity of this phospolipase on theregulation of sperm physiology. Second, I participated in the discovery of the gene DPY19L2involved in male infertility, globozoospermia. The globozoospermia is characterized by round headspermatozoa without acrosome. DPY19L2 gene is specifically expressed in the testis and is absent in80% of globozoospermic patients. I then identified the role of this protein, which is involved in theattachment of the acrosome to the nucleus. I showed that this protein belongs to the inner nuclearmembrane where it likely interacts with the protein sun5 which also belongs to the inner nuclearmembrane and whose expression is specific to spermiogenesis. Sun5 is involved in the complexformation, called LINC that connects the cytoskeleton to the nucleoskeleton lamina. The role ofDpy19l2 could help stabilizing the anchoring of protein sun5 in order to transmit the forces exertedby the cytoskeleton to the nucleus of the spermatid during acrosome spreading. Dpy19l2 belongs to aprotein family containing 4 members, Dpy19l1 to l4, which has not been poorly studied so far. Arecent study shows that the knock-down of Dpy19l1 resulted in defective glutamatergics neuronsmigration on the radial glia. The results obtained during my work would improve the knowledge ofCytoskeleton-nucleoskeleton interaction, and give new insight on this new family of proteins
Guezingar, Florence. "Evaluation du rôle du macrophage alvéolaire dans la distribution pulmonaire des oxydes d'actinides." Paris 11, 1999. http://www.theses.fr/1999PA11T054.
Actinide oxide inhalation is potentially a risk during the fuel fabrication process in the electronuclear industry. These particles can induce pulmonary lesions. The alveolar macrophage play an important role in the particle sequestration and transport but the actinide toxicity towards these cells is not weil known. The aim of this work was to characterize the evolution of particie localisation in lungs after inhalation and to evaluate the role of macrophages in the lesion histogenesis. We have used of a solid track detector to visualise alpha dose distribution with in lung tissue. After 237NpO2, MOX or PuO² inhalation by rats, different kinetics of clearance were observed for the subpleural and peribronchial areas compared to the others alveolar areas. For initial lung burdens that alter the lung clearance, particle aggregats were observed. Their kinetic and localization varie depending on the aerosol, for a same global dose delivered to the lungs. This could be due to the different specifie alpha activities of the particles and to the particle number deposited in the lung to obtain a similar burden but it could be also due to a chemical toxicity of neptunium higher than that of the others actinides. The flow cytometry methods developped allow us to measure apoptosis, phagocyosis and free radicals generation. After addition of soluble uranium to the culture medium, similar results were obtained using either alveolar macrophages extracted from rats or a macrophage cell line. This work confirms that alveolar macrophages are involved in the aggregat formation wich induce heterogeneous dose distribution within the different lung tissues
Perreault, Claudine. "Récepteurs du NPY au niveau des membranes de l'enveloppe nucléaire de l'endothélium endocardique humain rôle dans la régulation du calcium nucléoplasmique." Mémoire, Université de Sherbrooke, 2004. http://savoirs.usherbrooke.ca/handle/11143/3380.
Timcheva, Kalina. "Rôle de YTHDC1, lecteur nucléaire de la modification N6-méthyladénosine (m6A), dans la régulation de la réponse cellulaire au stress thermique." Thesis, Université Grenoble Alpes, 2020. https://thares.univ-grenoble-alpes.fr/2020GRALV011.pdf.
Over the years numerous studies unraveled the fascinating ability of the heat stress response (HSR) to act on the genome and to transiently control the cell proteome in order to preserve cell viability in the context of hostile environments. Nevertheless, the implementation and orchestration of the HSR today still hide mysteries. The implication of N6-methyladenosine (m6A) -the most abundant internal RNA modification- in the regulation of gene expression in response to stress has been recently uncovered. Yet, its importance, the associated functions and the involved mechanisms remain poorly characterized.During my PhD thesis I have studied the role of the protein YTHDC1, the main known nuclear reader of m6A, in the conserved cellular stress response to heat shock (HS). Therefore, my thesis work is at the crossroad of two main research axes- the emerging field of the epitranscriptome and the broadly investigated domain of stress biology. In this work, we were able to identify the central role played by YTHDC1, and by extension of the m6A signaling, in the regulation of the HSR pathway in human cells. First, we have demonstrated that during the recovery period following HS YTHDC1 massively relocalizes to characteristic nuclear structures appearing upon stress, named nuclear Stress Bodies (nSBs). This striking relocalization relies on the transcription of repetitive pericentric heterochromatin regions that produces the lncRNAs SATIII, which are at the core of nSBs formation. Importantly, we found out that beyond localizing at nSBs, YTHDC1, together with SATIII lncRNAs, contributes to the stress-induced regulation of alternative splicing events of potentially several hundreds of mRNAs. Second, by conducting ChIP-seq experiments we discovered that, upon HS, YTHDC1 is recruited to new genomic sites. Noticeably, we identified many Heat Shock Protein (HSP)-coding genes to be targets of YTHDC1 upon stress. Follow-up analyses revealed that YTHDC1 is essential for the induction of HSPs expression following HS. The investigation of YTHDC1 molecular functions showed that, under heat stress, the protein may regulate proper transcription termination of HSP genes and the following nuclear export of their mRNAs. Moreover, we found that, in response to stress, YTHDC1 is required to maintain the structure of Nuclear Speckles, which are membrane-less bodies contributing to the control of mRNAs fate. Finally, m6A-dependency of YTHDC1 molecular and cellular functions was addressed in this work through the establishment of a genetically manipulated cellular model. This approach demonstrated that some of the roles of YTHDC1 that we identified are associated with its ability to recognize the m6A RNA mark.In conclusion, this work has uncovered the epitranscriptome reader YTHDC1 as a novel and central regulator of the HSR acting at various levels of the stress-induced genome reprogramming in human cells. Our findings expand the current knowledge on the implementation of stress responses with the addition of a broadly acting layer of gene expression control and open new area of research for future studies
Tannour-Louet, Mounia. "Le récepteur nucléaire orphelin COUP-TFII et son rôle physiologique dans le métabolisme hépatique:implication dans la régulation transcriptionnelle par le glucose." Paris 11, 2002. http://www.theses.fr/2002PA11T021.
Ristea, Popescu Angela Iuliana. "Rôle du récepteur nucléaire FXR dans le métabolisme du glucose : étude de son expression, régulation et fonction dans le pancréas endocrine." Lille 2, 2009. http://www.theses.fr/2009LIL2S049.
Bezin, Stéphanie. "Rôle du NAADP et de son enzyme de synthèse, l'ADP ribosyl cyclase, dans les neurones : La régulation de l'homéostasie calcique nucléaire." Paris 11, 2007. http://www.theses.fr/2007PA11T086.
Mével, Marie. "Rôle de la kinase LKB1 dans les adénocarcinomes pulmonaires : régulations métaboliques et activité nucléaire, des mécanismes communs avec ses fonctions développementales." Electronic Thesis or Diss., Université Grenoble Alpes, 2023. http://www.theses.fr/2023GRALV103.
Lung adenocarcinomas (LUAD) are a subset of non-small-cell lung cancers, comprising approximately 85% of diagnosed lung cancer cases. The 5-year survival rate varies depending on the tumor stage, with approximately 68% survival for early-stage cases and nearly 0% survival for the most advanced stages. These cancers exhibit a range of mutational characteristics that may account for the varying degrees of severity. Liver Kinase B, abbreviated as LKB1, is found to be mutated in 8 to 21% of LUAD cases. While it is not the initiating factor in lung tumorigenesis, the loss of this protein significantly worsens the prognosis for affected patients.LKB1 is a serine-threonine kinase encoded by the STK11 gene, and it plays a pivotal role in the development and maintenance of various organs. Our team has uncovered essential metabolic regulations governed by LKB1 in distinct lineages of a specific embryonic stem cell population known as neural crest cells (NCCs). During my PhD, I contributed to investigating the significance of LKB1 in the establishment of the enteric nervous system—a complex network of ganglia responsible for regulating digestive motility and entirely derived from NCCs. Our research demonstrated the critical role of LKB1 in the differentiation of enteric neurons and the maintenance of enteric glial cells by limiting oxidative stress and modulating the activity of the p53 transcription factor.In this context, my doctoral research also delved into whether the metabolic regulations governed by LKB1 during NCC formation could also contribute to LKB1's tumor-suppressive activity. By conducting in silico analysis of transcriptomic data from LUAD patients with LKB1 mutations (in conjunction with oncogenic KRAS mutations), I have demonstrated that the loss of LKB1 function is linked to significant alterations in amino acid metabolism. Specifically, the expression of numerous enzymes involved in alanine metabolism is increased in the absence of LKB1 in lung adenocarcinomas. This increase aligns with data obtained from lung tumor cell cultures, which indicate higher levels of alanine in the absence of LKB1. Furthermore, LKB1 mutations are associated with dysregulation of metabolites and enzymes related to redox homeostasis, global epigenetic changes, as well as the stabilization of p53 and alterations in the expression of its target genes.Hence, my findings underscore the shared regulatory mechanisms between LKB1's developmental role in NCCs and its tumor-suppressive function in lung adenocarcinomas. These analyses, conducted in LUAD patients, further underscore the potential significance of LKB1 signaling in human developmental syndromes, even though mutations in this pathway are not currently associated with neurocristopathies—pathologies stemming from NCC malformations. Additionally, the identification of other dysregulations in LUADs, such as the regulation of oxidative stress via the NRF2-KEAP1 pathway and the deregulation of the transcription factor and chromatin regulator BRG1, reciprocally inspire a deeper understanding of LKB1's developmental functions. Collectively, these findings pave the way for exploring novel therapeutic strategies for conditions linked to diminished LKB1 signaling