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École doctorale Sciences de la vie et de la santé (Sophia Antipolis, Alpes-Maritimes)

Overview
Works: 676 works in 911 publications in 1 language and 941 library holdings
Roles: Other, Degree grantor, 996
Publication Timeline
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Most widely held works by Alpes-Maritimes) École doctorale Sciences de la vie et de la santé (Sophia Antipolis
Rôle de l'inflammation dans le développement de la stéatohépatite non alcoolique chez les patients obèses : interrelations entre le foie et le tissu adipeux by Adeline Bertola( Book )

2 editions published in 2009 in French and held by 3 WorldCat member libraries worldwide

Obesity is associated with hepatic complications ranging from steatosis to nonalcoolic steatohepatitis (NASH), fibrosis, cirrhosis and hepatocellular carcinoma. The pathophysiological mechanisms involved in the development of NASH remain poorly understood. In obesity, production of proinflammatory cytokines by adipocytes and adipose tissue- infiltrating macrophages may play a central role in the development of these hepatic complications. Using a large scale real-time quantitative PCR technique, we identified genes related to inflammation and immune response whose expression is altered in the liver of morbidly obese patients with NASH. These results suggest that immune response may be polarized towards a Th1 phenotype in the lover of these patients. Furthermore, we have identified immune semaphorins as potential new players in NASH. Recently, adipose tissue has been identified as a new source of osteopontin. This proinflammatory cytokine plays an important role in several murine models of liver diseases. We have shown that osteopontin expression is associated with adipose tissue inflammation and hepatic steatosis in morbidly obese patients. Our results suggest that osteopontin may contribute to macrophage infiltration into adipose tissue and that its enhanced expression during steatosis may be involver in the progression of hepatic complications. We have thus identified new players involved in the development of hepatic complication of obesity in humans
Caractérisation d'antigènes recombinants en vue du développement de tests ELISA discriminatoires de la fièvre Q chez les ruminants by Isabelle Fernandes-Rouviere( Book )

2 editions published in 2009 in French and held by 3 WorldCat member libraries worldwide

Q fever is a worldwide zoonosis due to Coxiella burnetii. Ruminants are the main source of human contamination by excretion of the bacteria into the environment. In ruminants, Q fever can provoke abortions and stillbirths. To diagnose Q fever in ruminants, several serological tests, based on whole bacteria as antigens, are available. These tests are poorly standardized and discordant results may be observed. Moreover, they cannot distinguish neither the different phases of infection nor the infected animals from the vaccinated. Hence, an ELISA test, based on recombinant antigens, would be useful to improve diagnosis of Q fever in ruminants. This work have identified such specific markers of infection or vaccination. The HspB protein would be a marker for recent infection and reactivation of infection. Furthermore, the AdaA protein have been tested for its capability to identify a Q fever abortion in ruminants. The use of this protein in ELISA could indicate a Q fever abortion. However, a gene variability have been observed among the C. burnetii strains studied: a duplication have been, for the first time, observed in some strains. Regarding the identification of vaccine protection markers, we have shown that the 27 kDa OMP could be an interesting marker. Lastly, regarding the bacterial excretion, we have also identified, by western blotting, potential markers linked to high excretion levels of C. burnetii in vaginal secretion. The analysis of these proteins, by protein microarray, are currently being processed. The results obtained during this study have permitted to see ways in the development of ELISA tests using recombinant antigens to diagnose Q fever in ruminants
Mise en évidence des propriétés immuno-régulatrices des complexes immuns du lait maternel : implications dans la prévention des maladies allergiques by Éric Mosconi( Book )

2 editions published in 2010 in French and held by 3 WorldCat member libraries worldwide

Au cours de ma thèse, j'ai étudié les mécanismes responsables de la tolérance immunitaire observée chez des souris nouveau-nés allaitées par des mères sensibilisées et exposées à un allergène pendant l'allaitement. Nous avons montré que ces mères, allergiques, préviennent la survenue d'asthme chez les nouveau-nés qu'elles allaitent et que cette protection persiste pendant plusieurs semaines après le sevrage. Ce phénomène est associé à un état de tolérance immunitaire causé par le transfert de complexes immuns IgG-antigènes de la mère au nouveau-né à travers la muqueuse intestinale. L'induction de tolérance est associée au développement de lymphocytes T régulateurs FoxP3+, dépend de l'expression du récepteur Fc néonatal (FcRn) chez le nouveau-né mais ne nécessite pas la présence de TGF-beta ou d'IgA dans le lait. Nous avons également montré que les complexes immuns du lait possèdent des propriétés tolérogènes intrinsèques liées à leur structure. Ces propriétés étaient inattendues, les complexes immuns étant classiquement décrits comme activateurs du système immunitaire. Nous avons montré que les complexes immuns du lait étaient constitués d'immunoglobulines possédant des résidus d'acide sialique à l'origine de leurs propriétés immunosuppressives. Ces complexes immuns sialylés sont capables de rendre tolérogènes des cellules présentatrices d'antigènes (CPA) en induisant leur sécrétion de TFG-beta, molécule à l'origine de l'induction des lymphocytes T régulateurs
Étude des relations fonctionnelles entre les toxines CNF1 et alpha-hémolysine (HlyA) des Escherichia coli uropathogènes by Mamady Diabaté( Book )

2 editions published in 2011 in French and held by 3 WorldCat member libraries worldwide

Cytotoxic necrotizing factor 1 (CNF1) and alpha-hemolysin (HlyA) are two major toxins of uropathogenic Escherichia coli (UPEC). UPEC are the major cause of urinary tract infection (UTI) and represent one of the main agents of bacteremia. These two toxins are usually associated to UTI because of their consistent presence in UPEC as compared to commensal strains of E. coli. Nevertheless, their physiological involvement in UTI remains unclear. Using a mouse model of bacteremia, we showed that CNF1 by its pro-inflammatory property can trigger host immune responses, thus allowing bacterial clearing from the blood by phagocytic cells. We also demonstrated that HylA has a cytotoxic effect on monocytes. This cytotoxic effect will counteract the production of pro-inflammatory cytotoxines induced by CNF1, and will allow the persistence of bacteria in mouse blood. According to this observation, we concluded that during bacteremia, CNF1 and HlyA have an opposite effect on bacterial persistence in the blood. We have developed a technique that allowed us to observe the effect of CNF1 in vitro, by directly infecting monocytes with CNF1 producing UPEC. We thus demonstrated that CNF1 can induce monocytes death during infection. Using a plasmid which produced a chimeric protein (CNF1-bêta-lactamase), we demonstrated that CNF1 can translocate from the bacterial cytoplasmic domain to the monocyte cytosol during infection. This work evidenced a functional interplay between two major virulence factors (CNF1 and HylA) as well as the effect of CNF1 on monocytes
Etude du mécanisme et de la régulation de la rotation corticale dans l'oeuf de xénope by Yannick Marrari( Book )

2 editions published in 2003 in French and held by 3 WorldCat member libraries worldwide

The cortical rotation in Xenopus eggs establishes the dorso-anterior organising center of the embryo. This translocation of the cortex relative to the cytoplasm starts when an array of aligned microtubules forms under the vegetal cortex, the plus ends of microtubules pointing in the direction of cortical displacement. The cortical rotation mechanism involves the two families of microtubule-dependant molecular motors, Kinesin Related Proteins and cytoplasmic dynein. The involvement of KRPs in cortical rotation mechanism was shown by the injection of a KRP inhibitory antibody which locally blocked cortical rotation, desorganised the subcortical array of microtubules and perturbed microtubule movement. The persistance of microtubule movement in the presence of the anti-KRP antibody in vivo, and the arrest of microtubule movement, reactivated by perfusion of ATP and interphase Xenopus egg extracts, provoked by simultaneous perfusion of anti-KRP and anti-dynein antibodies on isolated cortices led us to propose that dynein was also involved in the cortical rotation mechanism. Early injection of dynamitin, an inhibitor of dynein dependant transport, perturbed the organisation of sub-cortical microtubules while late injection did not arrest cortical translocation. These results indicate that dynein transports microtubules towards the cortex and maintains the microtubule array during an early period of the cortical rotation. Later, dynein activity becomes uneccessary, indicating that KRPs probably drive the cortical rotation. These findings led us to propose an integrated model for the mechanism of cortical rotation, in which dynein and KRPs have complementary actions
Rôle des cellules immunitaires et effets des cannabinoïdes dans la physiopathologie des maladies à prions by Sevda Cordier-Dirikoc( Book )

2 editions published in 2008 in French and held by 3 WorldCat member libraries worldwide

L'évènement moléculaire clé des maladies à prions est la conversion de la protéine prion cellulaire (PrPc) en une isoforme pathologique et résistance à la protéolyse, nommée (PrPres). La PrPres est responsable de la neuropathogenèse et de la transmissibilité de la maladie. La recherche de molécules capables d'inhiber sa formation dans le cerveau est donc une stratégie thérapeutique envisageable. Le cannabidiol, composé non psycho-actif de Cannabis Sativa, inhibe l'accumulation de la PrPres aussi bien in vitro qu'in vivo et permet de prolonger significativement le temps de survie des souris infectées par les prions. De nombreuses études suggèrent la participation des cellules immunes dans le transport de la PrPres. Grâce à un modèle de déplétion transitoire des cellules dendritiques, nous avons montré que ces cellules étaient impliquées dans le processus de lymphoinvasion après une infection par voie intra-péritonéale mais pas par voie orale. La fonction physiologique de la PrPc est encore mal connue, en particulier dans le système immunitaire. La recherche de partenaires protéiques pourrait permettre de mieux comprendre le rôle de la PrPc. Des traceurs fluorescents composés de PrP recombinante ont été produits et utilisés pour caractériser les sites de liaison de la PrPc dans les différentes populations de splénoctytes murins. La liaison des traceurs sur des lymphocytes B entraîne l'activation de la voie des MAP kinase et l'élévation transitoire de la concentration calcique intracellulaire démontrant que la liaison de la PrPc à ses récepteurs est fonctionnelle. Le rôle physiologique de ces interactions et la nature moléculaire des récepteurs reste à être déterminés
La phospholipase A2 sécrétée de groupe X : maturation protéolytique et rôles fonctionnels by Ikram Jemel( Book )

2 editions published in 2009 in French and held by 3 WorldCat member libraries worldwide

Les phospholipases A2 constituent une superfamille de protéines comprenant au moins onze phospholipases A2 sécrétées (sPLA2) et douze phospholipases A2 intracellulaires. Ces protéines catalysent l'hydrolyse des phospholipides en position sn-2, libérant un acide gras et un lysophospholipide. Elles contrôlent ainsi la production d'une variété de médiateurs lipidiques qui sont importants pour de multiples fonctions cellulaires dans différents contextes physiologiques ou physiopathologiques (maladies inflammatoires et cancer). La sPLA2 de groupe X a été clonée au laboratoire en 1997 et possède des propriétés moléculaires uniques. Son ARN messager est présent dans différents tissus, mais semble peu régulé par des stimuli proinflammatoires. L'enzyme est unique dans sa capacité à libérer des médiateurs lipidiques à partir des phopholipides cellulaires ou des lipoprotéines et possède aussi des propriétés antimicrobiennes variées. Un élément clé de la régulation fonctionnelle de la sPLA2 de groupe X est vraisemblablement lié à la présence d'un propeptide dans sa partie N-terminale. Le lieu de la maturation protéolytique de sPLA2 de groupe X (dans la cellule avant sécrétion ou à l'extérieur après sécrétion du proenzyme), les protéases impliquées et la régulation de cette maturation dans des conditions physiologiques ou physiopathologiques sont inconnus. Le travail de cette thèse a permis de mieux comprendre comment peut s'effectuer la maturation de la sPLA2 de groupe X et quels sont ses rôles physiologiques et physiopathologiques. Concernant la maturation, nos études in vitro sur protéines purifiées et en cellules transfectées (HEK293) ont permis de montrer qu'une protéase de type furine contribue de façon majeure à l'activation de l'enzyme, vraisemblablement au cours de sa sécrétion. Nos travaux suggèrent aussi qu'une maturation est possible par d'autres protéases et dans le milieu extracellulaire comme par exemple dans les cellules LOVO. Nous avons aussi tenté de mettre en évidence cette maturation dans des tissus murins dans certaines conditions physiologiques et physiopathologiques. Nous avons notamment trouvé que la sPLA2-X était la sPLA2 majeure présente dans l'acrosome des spermatozoïdes. Enfin nous avons observé un polymorphisme présent dans le propeptide de la sPLA2 humaine qui conduit à la formation d'une protéine inactive et rapidement dégradée. Dans la deuxième partie de cette thèse, nous avons montré que la forme active de la sPLA2 de groupe X, mais pas son proenzyme était capable i) de stimuler la prolifération cellulaire dans un contexte de cancer colorectal, ii) d'exercer une action toxique contre le parasite de la malaria P. falciparum lors de l'infection de globules rouges humains, et iii) de contrôler la réaction acrosomique des spermatozoïdes de souris, avec un impact important sur le taux de fécondité dans des tests de fécondation in vitro
MITF contrôle la voie de réponse de dommage à l'ADN et la sénescence des cellules de mélanome by Sandy Giuliano( Book )

2 editions published in 2011 in French and held by 3 WorldCat member libraries worldwide

Malignant melanoma is an aggressive cancer known for its notorious resistance to most current therapies. The basic helix loop helix Microphtalmia transcription factor (MIRF) is the master regulator determining the identity and properties of the melanocyte lineage and is regarded as a lineage-specific “oncogene” that plays a critical role in the pathogenesis of melanoma. Here we report that depletion of MITF in melanoma cells triggers a lineage-restricted program of senescence characterized by typical morphologic and biochemical changes associated with a sustained growth arrest. Our findings demonstrate that MIRF silenced cells engage a DNA damage response (DDR) that is critically required for senescence entry. More importantly, engagement of the DDR machinery allows MITF to control the endogenous level of the tumor suppressor p53 and we show that p53 loss antagonizes the senescence program. By combining ChIP-seq and RNA-seq analyses, we identify that MITF regulates a set of genes required for DNA replication, repair and mitosis. Particularly we identified survivin a chromosomal passenger protein as a new target of MIRF. Down regulation of several of these genes trigger mitotic defects suggesting that similar effects should be observed upon MITF inhibition. We show that MITF or surviving depletion triggers aberrant karyokinesis and cytokinesis and promotes cellular senescence. We propose a model of mitotic errors caused by inhibition of surviving after invalidation of MITF which lead to DNA damage and a program of senescence. These findings shows that MITF acts an anti-senescence factor and reveal a lineage-specific control of cell division through surviving regulation providing new avenues for therapeutic intervention in melanoma
Mécanismes de régionalisation de l'embryon d'oursin le long des axes animal-végétatif et oral-aboral by Jenifer Croce( Book )

2 editions published in 2003 in French and held by 3 WorldCat member libraries worldwide

In the sea urchin embryo, a traditional model in Developmental Biology, the establishment of the germ layers involve many genes whose generally encoded components of signalling pathways. We have isolated three different T-box transcription factors : ske-T, Brachyury and coquillette. The expression pattern of ske-T and coquillette and the functional analysis of coquillette indicate that these two genes are implicated in the skeletogenesis. Brachyury, which is expressed in a dynamic pattern in the invaginating cells at the two ends of the archenteron, seems to play a crucial role during gastrulation. The zygotic expression of Frizzled, the receptor of the Wnt ligands, is spatially restricted. It is detected at the animal pole and in a ring of cells around the vegetal pole which later form the tip of the gut. The overexpression of dominant-negatives forms of Frizzled does not interfere with the initial specification of the main territories but it blocks the formation of the gut and perturbs the organization of the skeleton. Frizzled seems to be required for the cellular movements that occur during gastrulation and skeletogenesis. The NLK kinase is successively expressed in the precursors of the primary mesenchyme cells, secondary mesenchyme cells, in the endodermic cells and in some ectodermic cells. The perturbations caused by the overexpression of the wild type form of this kinase reveal that it should act in synergy with Notch signalling. Nlk appears to be involved in specification of the secondary mesenchyme cells and in the establishment of the embryonic borders
Le cluster miR 302-367 : inhibiteur des propriétés tumorales des cellules souches cancéreuses issues de glioblastomes humains by Mohamed Fareh( Book )

2 editions published in 2011 in French and held by 3 WorldCat member libraries worldwide

Glioblastoma multiforme (GBM) is the most common form of primary brain tumor in adults, often characterized by poor survival. Glioma-initiating cells (GICs) are defined by their extensive self-renewal, differentiation, and tumor initiation properties. GICs are known to be involved in tumor growth and recurrence, and in resistance to conventional treatments. One strategy to efficiently target GICs in GBM consists in suppressing their stemness and consequently their tumorigenic properties. In this study, we show that the miR-302-367 cluster is strongly induced during serum-mediated stemness suppression. Stable MiR-302-367 cluster expression is sufficient to suppress the stemness signature, self-renewal, and cell infiltration within a host brain tissue, through inhibition of the CXCR4 pathway. Furthermore, inhibition of CXCR4 leads to the disruption of the sonic hedgehog (SHH)-GLI-NANOG network, which is involved in self-renewal and expression iof the embryonic stem cell-like signature. In conclusion, we demonstrated that the miR-302-367 cluster is able to efficiently trigger a cascade of inhibitory events leading to the disruption of GICs stem-like and tumorigenic properties. Our studies have shown a paracrine effect tumor suppressor related to the overexpression of miR-cluster 302-367 in the GICs. This paracrine effect of GICs-miR is mediated by the secretion of exosomes containing IL-8 and miR-302-367. This paracrine effect can alter the expression of stemness markers, clonogenicity and proliferation of GICs-Ctrl and consequently compromise their tumorigenic properties in vivo
Mise au point d'un modèle ex-vivo d'étude de l'immunité innée des anticorps naturels lors de l'ischémie-reperfusion rénale by Marc Gigante( Book )

2 editions published in 2008 in French and held by 3 WorldCat member libraries worldwide

The participation of innate immunity mediated by natural autoreactive an polyreactive IgM antibodies is shown in recent developpements of ischemia reperfusion injury. The purpose of this thesis was to settle an ex-vivo model to confirm this theory. Lymphoblastic cells lines (LCLs) were established with infection by Eptein-Barr Virus (EBV) associated with unmethylated single-stranded DNA motifs (CpG oligonucleotides) as an antigenic stimulus. For each subtype of B Cell (Transitional, Mature naive and Memory), the effect of immortalization on phenotypic markers was studied in flowcytometry. The production of immunoglobulin was estimated by ELISA as well as the Polyreactivity of these antibodies. Autoreactivity was appreciating by an ana HEP-2 test. On the other hand, an ex-vivo normothermic reperfusion device was built using a modified (oxygenation an temperature control) perfusion pulsatile machine (MOX 100 or RM3). All 4 subtypes of B-cells from human peripheral blood were transformed into actively proliferating lymphoblastoid cell lines. he effect of transformation were relevant for 8 out of 16 studied phenotype markers: CD5, CD10, CD23, CD24, CD27, CD38, IgD, IgM. Immunoglobulin secretion : IgM, IgA or IgG can be secreted, but no IgD. The type of Ig secreted differs according to the original subtype of B-Cell. There is a very strong and coherent link between Ig membrane expression and Ig secretion. Some LCLs were secreting IgM type autoreactive antibodies. Ther were no IgA or IgG type autreactive antibodies. Some LCLs were secreting IgM type polyreactive antibodies. We succeed in building a ex-vivo normothermic reperfusion kidney device with an active diuresis of 6 hours. We succeed in building a ex-vivo normothermic reperfusion kidney device with an active diuresis of 6 hours in order to study Innate immunity mediated by Natural IgM during ischemia reperfusion injury. Mass production of autoreactive an polyreactive antibodies for this model is possible
Le microchimérisme foetal chez la femme urémique avant et après transplantation rénale by Laetitia Albano( Book )

2 editions published in 2008 in French and held by 3 WorldCat member libraries worldwide

Fetal microchimerism (Mc) is the presence of a small amount of fetal cells or DNA in the mother's circulation. This is a common sequel of pregnancy in any gravid woman and can persist decades after delivery. First part : Better prognosis in women with end stage renal diseases (ESRD) compared to men, triggered us to analyze the potential “protective” role of microchimerism acquired after pregnancy in women before kidney transplantation. We studied the prevalence of male DNA in PBMC, by quantitative PCR method, in 55 women with ESRD prior to their first kidney transplantation and 82 healthy women as controls. Male Mc was also quantified in 5 native kidney biopsies obtained prior to blood testing and in PBMC from 8 women collected after female kidney transplantation. Women with ESRD showed statistically higher frequencies (72%) and quantities (98 genome equivalent per million, gEq/M) of male Mc in their PBMC than healthy women (27% and 0.3 gEq/M, p<0.0005). Moreover, 3 out of 5 renal biopsies contained Mc in small quantities. Finally, few years after kidney transplantation, Mc was totally cleared from PBMC in all women tested but one. As a possible scenario, fetal cells might be recruited and proliferate in women with ESRD under inflammatory factors and then play a role in tissue repair, explaining in part the better prognosis of women in disease progression. Further studies are needed to elucidate mechanisms of recruitment and persistence of Mc in ESRD women. Second part: Microchimerism (male), Human Leucocyte Antigen (HLA) antibodies (Ab), and major-histocompatibility-complex class I-related chain A (MICA) Ab in peripheral blood may occur after pregnancy and/or transfusion and/or allotransplantation. We questioned about a potential relationship between these three phenomena. We enrolled 46 women, selected in accordance to anti-HLA immunization, previously pregnant and/or transfused and wait-listed for a first kidney graft. Pretransplant HLA-Ab were present in 24/46 (52%) and anti-MICA Ab in 6/46 (13%). Microchimerism was detected by the presence of Y chromosome DNA using a specific nested-PCR SRY and a quantitative PCR DYS14 method. We have not found a significant association between male microchimerism and HLA-Ab positivity but the level of Mc seems to influence the range of PRA class I and II and MICA Ab production. microchimerism and HLA-Ab production are two co-existing phenomena and not exclusive in women with end-stage renal failure awaiting a first kidney transplantation. More specific techniques shoud be used to determine the target specificity of both mechanisms and to be able to answer an unresolved important question: could the specific epitope(s) be identical?
Métabolisme et cancer : cibler le métabolisme des cellules cancéreuses par des agents inducteurs du stress métabolique by Issam Ben-Sahra( Book )

2 editions published in 2010 in French and held by 3 WorldCat member libraries worldwide

Les maladies métaboliques comme le diabète sont associées à une incidence plus importante de certains cancers. En effet, la metformine, un médicament couramment prescrit contre le diabète de type II inhibe la croissance des cellules cancéreuses de prostate et ralentit la croissance tumorale en induisant un arrêt du cycle cellulaire en G0/G1. Cet effet s'accompagne d'une inhibition de la voie mTOR indépendamment de l'AMP Kinase, un régulateur majeur du métabolisme de la cellule. Bien que la Metformine active la voie AMPK, celle-ci n'est pas impliquée dans son effet antiprolifératif. Nous avons montré que REDD1 est la protéine médiatrice de cette action antiproliférative. De plus, nous montrons que la metformine ralentit significativement la croissance tumorale chez la souris nude. Afin d'augmenter l'action anti-tumorale, nous avons combiné la metformine, un inhibiteur du complexe I avec le 2-déoxy-D-glucose (2-DG), un inhibiteur de la glycolyse. Cette combinaison bloque de façon drastique la croissance cellulaire et induit l'apoptose des cellules cancéreuses de prostate. De plus nous montrons que cette induction de l'apoptose s'accompagne d'une suppression de l'autophagie induite par le 2-DG seul. Ainsi nos travaux montrent que la metformine seule ou en combinaison avec le 2-DG pourraient représenter un intérêt thérapeutique important dans le traitement du cancer de la prostate
Etude spatio-temporelle de la chimie de l'endolymphe en relation avec la calcification de l'olithe chez les poissons téléostéens by Gil Borelli( Book )

2 editions published in 2001 in French and held by 3 WorldCat member libraries worldwide

Otolith is a composit biomineral (CaCO3 99,9% and organic matrix 0,1%) localized in the inner ear of teleost fishes. It is involved in equilibration and hearing functions. The otolith growth is a cyclic process synchronised on the circadian rhythm and takes place in the acellular endolymph fluid. Most of endolymphatic elements (Na+, K+, Ca tot, pH, CO2 tot, Mg2+, PO43- and proteins, collagens, proteoglycans, amino-acids) show a lack of uniformity in the endolymph. Spatial distribution of endolymphatic gradients (proximo-distal) is in relation to the cellular diversity of the saccular epithelium (7 cellular types). The endolymphatic protein secretion and the paracellular Ca2+ influx take place in the proximal area. Organic and ionic gradients contribute in the otolith composition and growth. Anticalcifying activity of endolymph avoid uncontrolled precipitation of CaCO3. During the nycthemeral cycle, the variation of proteins and collagens concentrations in endolymph likely induce the rhythmicity of organic matrix formation and CaCO3 deposition. We studied the endolymphatic composition during 2 environmental conditions (starvation and Cl2 stress) known to modify the otolith growth. Our results allow to establish an integrative model for the otolith calcification with a special emphasis with the Ca2+ flux, acido-basic and calcifying parameters
Déficits de la chaîne respiratoire mitochondriale avec instabilité de l'ADN mitochondrial : identification de nouveaux gènes et mécanismes by Cécile Rouzier( Book )

2 editions published in 2012 in French and held by 3 WorldCat member libraries worldwide

Les mitochondriopathies liées à un défaut de stabilité de l'ADN mitochondrial (ADNmt) représentent un nouveau volet dans les affections liées à un déficit de la chaîne respiratoire. Cette instabilité se traduit par des délétions multiples et/ou une déplétion (diminution du nombre de copies) de l'ADNmt. Ces pathologies sont caractérisées par une importante hétérogénéité clinique et génétique et sont secondaires à des mutations dans des gènes nucléaires codant pour des protéines impliquées dans le maintien du génome mitochondrial. Le gène POLG1, qui code pour la sous-unité catalytique de la polymérase gamma, est le gène le plus fréquemment impliqué. A ce jour, la recherche de mutations dans ce gène ou d'autres gènes connus, responsables de délétions multiples et/ou déplétion de l'ADNmt, s'avère négative dans plus de 70% des cas, d'où un grand intérêt pour améliorer les techniques d'identification des mutations et la recherche de nouveaux gènes impliqués dans ces pathologies. Mon travail de thèse a consisté d'une part, à identifier de nouveaux gènes responsables d'une instabilité de l'ADNmt et à caractériser certains mécanismes à l'origine de cette instabilité et d'autre part, à mettre en place une nouvelle technique d'analyse du gène POLG1 afin d'identifier des mutations à type de grands réarrangements, délétion et/ou duplication. Dans une première partie, nous avons analysé deux patients non apparentés porteurs de déplétion de l'ANmt associée à un déficit généralisé de la chaîne respiratoire mitochondrial présentant un tableau clinique et biologique évocateur d'un déficit en succinate CoA ligase. Chez ces patients, nous avons pu identifier des mutations du gène SUCLG1 confirmant l'implication de ce gène dans les encéphalomyopathies avec déplétion de l'ADNmt. Nous avons également mis en évidence une corrélation entre la sévérité du phénotype et la quantité résiduelle de protéine SUCLG1. Nous avons également analysé une famille dont plusieurs membres étaient atteints d'atrophie optique associée à une myopathie mitochondriale, avec délétions multiples de l'ADNmt, dont la ségrégation était évocatrice d'une transmission autosomique dominante. Nous avons identifié une nouvelle mutation du gène MFN2, impliqué dans la fusion mitochondriale, et responsable de la majorité des maladies de Charcot-marie-Tooth de type 2A. Nous avons ainsi décrit MFN2 comme nouveau gène d'instabilité de l'ADNmt et confirmé l'implication de la fusion mitochondriale dans la stabilité de l'ADNmt. De plus, nous avons montré qu'un défaut de réparation de l'ADNmt participe aux instabilités de l'ADNmt par défaut de fusion mitochondriale. Enfin, nous avons mis au point une nouvelle technique d'analyse du gène POLG1 par QMPSF (Quantitative Multiplex PCR of Short fluorescent Fragments), permettant de mettre en évidence des anomalies quantitatives. Cette technique nous a permis d'identifier une délétion à l'état hétérozygote chez une enfant présentant une encéphalopathie épileptique chez qui nous avions identifié au préalable, par séquençage, une seule mutation pathogène à l'état hétérozygote du gène POLG1. Nous avons ainsi montré l'intérêt de compléter l'analyse du gène POLG1 par la recherche de grands remaniements chez les patients porteurs d'une seule mutation à l'état hétérozygote avec une clinique très évocatrice
Caractérisation de la mort indépendante des caspases : mécanismes et importance physiologique dans le développement des lymphocytes T by Marie Jacquin( Book )

2 editions published in 2012 in French and held by 3 WorldCat member libraries worldwide

Cell Death can be engaged either by apoptosis, a caspase-dependent mechanism or by Caspase-Independent Cell Death, so called CICD. We recently described that this new type of cell death can be specifically inhibited by a glycolytic enzyme, GAPDH that promote cell survival and proliferation. The first part of my work was to characterize the signaling pathway induced by GAPDH in order to protect cells from CICD. We showed that GAPDH-overexpression, but no other glycolytic enzymes tested, could stabilize active Akt through an interaction limiting its dephosphorylation. Active Akt prevented FoxO nuclear localization that precludes Bcl-6 expression and leads to Bct-xL overexpression. Thus, our work suggests that GAPDH overexpression could protect cells from CICD-induced chemotherapy through the preservation of intact mitochondria. The second part of my work was to identify CICD occurrence in vivo. We generated transgenic mice overexpressing GAPDH specifically in T cells (under the control of LCK promoter). These mice showed an impaired development of the immune system T lymphocytes accumulation in the thymus, a splenomegaly and an increase in circulating lymphocytes. Mice finally develop aggressive B lymphomas. Then, we analyzed the effect of concomitant overexpressing mice. This study showed that CICD plays an important role in T cell development and highlighted for the first time to our knowledge that CICD occurs in vivo
Adaptation d'une résine de scellement à l'émail des puits et fissures : influence de trois techniques de préparation : études in vitro by Laurence Lupi-Pégurier( Book )

2 editions published in 2004 in French and held by 3 WorldCat member libraries worldwide

This in-vitro study was divided into 4 parts. All teeth were cleaned with a brush without pumice.Microleakage tests were conducted on 270 third molars. The same sealant was applied on all teeth according to the manufacturer's recommendations. The teeth were thermocycled prior to staining in a methylene blue dye solution. The extent of microleakage was assessed thanks to a digital image analyser. Sealants placed after the use of the studied techniques alone (AA, SA, L) exhibited a significantly higher number of teeth showing microleakage. They also displayed highest means of microleakage. No difference was detected between the samples when acid etching was performed, whatever the enamel preparation applied before was. 2- The same cuts were used to assess the penetration of the sealant in pits and fissures. More than seventy-five percents of the sealants in each group showed a complete penetration. Neither paired nor unpaired comparisons revealed any significant difference in the filling rates according to the enamel preparation (p>0.05). Whatever the surface treatment was, the filling rates of fissures were high (>90%). 3- SEM observations were conducted on 48 molars to study the enamel, the backs of the sealants and the enamel-sealant interfaces after the different enamel preparations. Microphotographs revealed a very rough and irregular surface when the techniques were used alone. L irradiation induced the formation of numerous micro-cracks that penetrated in the depth of enamel. When acid etching was performed, the enamel surface was always regular and the honey-comb appearance visible. Observations of interfaces showed that real resin-tags could not be individualized between material and enamel when the techniques were used alone. On the contrary, they were clearly visible when acid etching was performed. 4- Lastly, 80 molars were used to study the wettability of enamel surfaces after these different preparations. AA and SA used alone showed the poorest results. Acid etching increased both the free surface energy and the wettability, except in the case of the Er:YAG laser, for which the contact angle was close to zero even without acid etching. Even if it dos not eliminate the need for etching the enamel surface prior to sealant application, the AA method, appears to be very interesting
Régulation des molécules HLA de classe I classiques et de CD1a : rôle de la molécule CD99 au cours de la génération de cellules dendritiques by Karim Mahiddine( Book )

2 editions published in 2010 in French and held by 3 WorldCat member libraries worldwide

Dentritic cells (DCs) are the most effective Antigen Presenting Cells (APCs), playing a major role on the activation of CD1a-restriced T-cells. This activation requires expression of CD1a molecule at the DC plasma membrane. Here we report that CD1a transcription and expression is regulated by a mechanism including both long and short CD99 isoforms (CD99LF and CD99SF). We provide here that CD1a transcription is allowed by a switch expression form CD99LF to comparable expression of both CD99 isoforms during the iDCs differentiation process in vitro. In this study, we demonstrate that CD99LF maintains a lower level of CD1a transcription by up-regulating the phosophorylated form of ATF-2 transcription factor. The CD99SF is required for counteracting this regulatory mechanism. We also suggest that the CD99LF induced mechanism is probably not restricted to CD1a, but is extended to classical MHC class I transcription, by modulating CREB-1 phosphorylation level. Elucidation of molecular mechanisms related to CD99 alternative splicing could be very helpful in the aim to have a better understanding of the transcriptional regulatory mechanism of CD1a and class I molecules during the DCs generation and activation steps
Régulations et recherche de nouveaux partenaires des protéines SOCS by Pierre Gontard( Book )

2 editions published in 2010 in French and held by 3 WorldCat member libraries worldwide

SOCS (Suppressor Of Cytokine Signaling) proteins are expressed in response to cytokines and hormones. Generally speaking SOCS exert a negative feedback on signaling pathways, which induce their expression. Thus, SOCS proteins are potent inhibitors of insulin signal and dysregulation of their expression and/or action could play a key role in insulin resistance and diabetes. During my PhD, I first identified microRNAs targeting SOCS-1, -2 and -3 mRNAs and potentially implicated in the regulation of SOCS expression. In addition, to specify the molecular mechanisms driven by SOCS proteins, I planed to define new partners of SOCS-3. Thus, I demonstrated that the phosphatase calcineurin interacts with SOCS-3 in vitro and in vivo. In transgenic mice expressing constitutively SOCS-3 in skeletal muscle, this association is illustrated by a colocalization of calcineurin and SOCS-3 leading to the delocalization and sequestration of calcineurin at the periphery of muscle fibers. In correlation with altered calcineurin function, a decreased locomotor activity is observed in transgenic animals. Since it was known that skeletal muscle is able to synthesize and secrete molecules, I wanted to determine whether constitutive expression of SOCS-3 in muscle could alter its secretive function. My analysis showed that whereas increased circulating levels of Interleukin-6 (partially produced by skeletal muscle) are detected in control animals under a high fat diet, no variation is observed in transgenic mice. My investigations brought new insights into the molecular mechanisms driven by SOCS and suggested a new role for SOCS proteins, beside their repressive function, as signaling molecule
Étude d'un marqueur électrophysiologique de vulnérabilité à la schizophrénie : l'onde P50 des potentiels évoqués auditifs by Sandrine Louchart de La Chapelle( Book )

2 editions published in 2010 in French and held by 3 WorldCat member libraries worldwide

Progress in radiation protection and radiotherapy, and the increased needs in terms of accuracy lead national metrology institutes to improve the standard. For ionizing radiation, te standard is defined by an absolute instrument used for air kerma rate measurement. The aim of the thesis is to establish standard, in terms of air kerma for X-rays beams of low and medium-energies. This work enables to complement the standard beam range of the Laboratoire National Henri Becquerel (LNHB). Two free-air chambers have been developed, WK06 for medium-energy and WK07 for low-energy. The air-kerma rate is corrected by several correction factors. Some are determined experimentally, and the others by using Monte Carlo simulations. The uncertainty budget of the air-kerma rate at one standard deviation has been established. These dosimetric standards were compared with those of counterparts' laboratories and are consistent in terms of degree of equivalence
 
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Alternative Names
École doctorale 85

École doctorale de biologie et pharmacologie moléculaires (Sophia Antipolis, Alpes-Maritimes)

ED 085

ED 85

ED085

ED85

EDBIO

EDSVS

Université de Nice-Sophia Antipolis. Ecole doctorale de biologie et pharmacologie moléculaires

Université de Nice-Sophia Antipolis. EDBIO

Languages
French (40)