WorldCat Identities

École doctorale Environnements, Santé (Dijon / Besançon) (2012-....).

Works: 467 works in 812 publications in 2 languages and 813 library holdings
Roles: Other, Degree grantor, 996
Publication Timeline
Most widely held works by Santé (Dijon / Besançon) (2012-....) École doctorale Environnements
Conséquences de la mise en place des bandes enherbées sur l'évolution de la flore adventice by Stéphane Cordeau( Book )

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

The intensification of the management of weed populations, led by a potential decrease in the yield and quality of crop harvest, has largely induced their decline in arable zones across the last decades. This floristic decline in arable landscape, has induced a loss of a larger biodiversity because the presence of others organisms (birds, insects, mammals) are strongly linked with the abundance of trophic resources as weed are. To counter with this loss of biodiversity and to limit the negative impacts of farming practices on environment, numerous agri environmental schemes were launched through Europe. In France, sown grass strips were established by farmers along streams and rivers to limit the pesticide drifts and the hydric soil erosion. The field margin strips are mainly sown with grass mixtures and do not receive neither pesticides nor fertilizers. Consequently, their establishment in the arable landscape for many years, without compensation payments for farmers, spark many fears concerning the weed risk that they could represent for adjacent field. At the opposite, these non-cropped areas adjacent to cultivated fields could be an opportunity to maintain weed populations providing ecosystem services for agriculture which were more and more highlighted.This PhD work shows that sown grass strips harbour large flora diversity. The weed communities are mainly structured by the type of adjacent boundary (hedge, river, ditch, etc.). The succession of disturbance and competition phase caused by mowing and competition of sown species respectively, do not allow annual species to maintain their populations in this habitat where they rarely reach fructification stages. The frequently observed species are perennials but rarely dominated over the sown cover. Even if the sown grass strips show high level of species richness, mainly composed by arable species, these strips do not enhance the spread of species from the boundary to the field core. Indeed, at least at short term, the sown grass strips decrease the edge effect because they were established where the flora transition between the boundary and the field previously occurred. Moreover, the establishment and management practices cost for farmers, reasonably at the farm scale.Although some fears on the decline of annual species, the sown grass strips represent an opportunity for the weed management at the field scale as well as at the landscape scale. Joint study linking the flora with other organisms (soil microflora, grasshoppers) have been initiated and could allow to put the environmental sown grass strips to good use for biodiversity
Implications du stress oxydant et du fer dans la cardiotoxicité des anthracyclines et du trastuzumab by Charles Guenancia( )

2 editions published in 2015 in French and held by 3 WorldCat member libraries worldwide

Notre deuxième travail expérimental visait à élucider le rôle de la surcharge pondérale dans le développement de la cardiotoxicité des anthracyclines et du trastuzumab. Grâce à un modèle murin de surpoids modéré et de risque cardio-métabolique accru induits par programmation post-natale, nous avons mis en évidence le rôle potentiateur d'une surcharge pondérale sur le développement de la cardiotoxicité aux anthracyclines ; alors que la cardiotoxicité du trastuzumab ne semble pas être en revanche majorée par le surpoids. Nos travaux ont également permis de préciser les conditions dans lesquelles existent des potentialisations des effets lors de l'association doxorubicine et trastuzumab
Caractérisation de nouvelles cibles de LXR et impact sur le métabolisme lipidique et l'athérosclérose by Alexis Varin( Book )

2 editions published between 2014 and 2016 in French and held by 2 WorldCat member libraries worldwide

Les récepteurs nucléaires LXR[alpha] et LXR[beta] sont activés par la fixation de dérivés oxygénés du cholestérol. Ils régulent l'expression de nombreux gènes appartenant au métabolisme du cholestérol et des acides gras, et jouent un rôle important dans l'inflammation et l'immunité innée. L'activation de LXR inhibe le développement de l'athérosclérose, en augmentant l'efflux de cholestérol des macrophages ainsi que le transport inverse jusqu'au foie et l'excrétion biliaire. De plus, LXR diminue la biosynthèse et la captation du cholestérol dans les tissus périphériques. Enfin, les agonistes synthétiques de LXR administrés à des souris diminuent significativement l'inflammation dans les lésions athérosclérotiques, notamment en inhibant la sécrétion de certaines cytokines inflammatoires. Néanmoins LXR régule également la lipogenèse et la synthèse d'acides gras mono-insaturés, et l'administration d'agonistes de LXR s'accompagne également d'effets indésirables liés à cette régulation, comme une accumulation dérégulée d'acides gras dans le foie et une augmentation du taux de LDLs circulantes. Plusieurs autres mécanismes restent encore à être explorés, comme la synthèse d'acides gras polyinsaturés et les conséquences sur le métabolisme cellulaire. Nos travaux identifient une nouvelle voie régulée entièrement par LXR, le métabolisme des acides gras polyinsaturés. Le récepteur nucléaire LXR régule l'ensemble des enzymes FADS1, FADS2 et ELOVL5, responsables de la synthèse d'acides gras polyinsaturés oméga-6 et oméga-3. Cette régulation s'accompagne d'une incorporation d'acide arachidonique dans les phospholipides, via la régulation de LPCAT3, ce qui prépare les macrophages à une synthèse accrue de dérivés inflammatoires issus de l'acide arachidonique, comme la Prostaglandine E2, suite à une stimulation au lipopolysaccharide. La régulation de cette voie par LXR a également un effet sur le développement de l'athérosclérose, augmentant les taux d'acides gras polyinsaturés oméga-6 et oméga-3 dans les plaques d'athérome. Nos résultats montrent donc que LXR régule la synthèse des acides gras polyinsaturés en plus des acides gras mono-insaturés et de la lipogenèse et que cette régulation a des conséquences sur le profil lipidique des macrophages in vitro et in vivo ainsi que sur leur réponse inflammatoire
Calcium signaling in plant defense : involvement of subcellular compartments and glutamate receptors by Hamid Manzoor( Book )

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

Plants do not display an adaptive immune system but express an efficient innate immune system defending them by inducing sophisticated multilevel defense responses against different potential pathogens. Indeed, plant immune responses are triggered upon the detection of many common pathogen- or microbe-associated molecular patterns (PAMPs/MAMPs) through specific pattern-recognition receptors (PRRs) and/or pathogen- or plant-derived signal molecules called elicitors. Cryptogein (Cry) and oligogalacturonides (OGs) are well known elicitors of defense reactions and their recognition induce a Ca2+-dependent signaling pathway: Ca2+ influx and subsequent free cytosolic [Ca2+] ([Ca2+]cyt) variations are earliest steps to trigger downstream plant defense signaling. Here we have demonstrated that elicitor-induced Ca2+ signaling in tobacco also takes place in mitochondria and chloroplasts. Pharmacological studies indicated that IP3-channels play an important role in the regulation of Ca2+ signaling in mitochondria and chloroplasts. Mitochondrial respiration and energy dissipation mechanisms in chloroplasts are partly controlled by [Ca2+] in these organelles. Moreover, using pharmacological and genetic approaches, our data demonstrated that glutamate receptors homologs (GLRs) participate in OGs-mediated Ca2+ signaling in Arabidopsis. GLRs partly control OGs-induced nitric oxide (NO) production, reactive oxygen species (ROS) production and expression of defense-related genes. Importantly, plants treated with GLRs antagonists exhibited compromised resistance to necrotrophic fungal pathogen, Botrytis cinerea and biotrophic oomycete, Hyaloperonospora arabidopsidis. Analysis of Atglr single mutants revealed the important contribution of AtGLR3.3 in resistance against H. arabidopsidis. Moreover, striking similarities in gene expression levels were observed after OGs elicitation/H. arabidopsidis infection. Finally, transcriptomic analysis demonstrated that about 60 % of the total OGs-modulated genes modified their expression in GLRs-dependent manner. These GLRs-dependent genes belong to different functional categories including the category “responses to biotic stresses”. Taken together, these data provide strong evidences of 1) elicitor-induced Ca2+ signaling in mitochondria and chloroplasts in tobacco and 2) the regulation of elicitor/pathogen mediated plant defense signaling pathways through GLRs in Arabidopsis thaliana
Facteurs de contrôle extrinsèques des dépôts microbiens récents en domaine de transition continental-marin by Anthony Bouton( Book )

2 editions published in 2016 in French and held by 2 WorldCat member libraries worldwide

Lithified microbial deposits, considered as microbialites, are organosedimentary structures observed since 3.5 billion years. Understanding the mechanisms and environmental conditions leading to their formation may provide valuable information about the origin of life on Earth. Our interest on this research topic has increased owing to the economic implications of these deposits, especially concerning the hydrocarbons. The reconstruction of the environments associated with microbial structures remains uncertain in the fossil record, especially between marine and continental domains. These two contrasting environments were studied through two modern examples: (1) a marine-fed lagoon area in Cayo Coco (Cuba), and the continental lake of the Great Salt Lake (Utah, USA) in order to identify diagnostic criteria allowing to distinguish both environments in the fossil record.Microbialite result from mineralization and lithification of microbial mats under the influence of metabolic chemical reactions (intrinsic) related to the activity of the microbial biomass and environmental (extrinsic) conditions. The objective of this PhD is to replace microbial deposits, at different scales, in their context of formation to highlight the significance of extrinsic parameters on: (1) the mineralization processes and the formation of microbialites, (2) the morphologies of observed microbial structures, (3) their spatial distribution, and (4) the relationship between microbial mats and microbialite and their environment
Ecological role of mycotoxins produced by Fusarium graminearum : consequences of the presence of deoxynivalenol (DON) in crop residues on the soil microflora and soil fauna by Muhammad Abid( Book )

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

Fusarium graminearum is a plant pathogenic fungus, causing devastating disease “Fusarium head blight” (FHB) in cereals including wheat and maize. It also contaminates the grains with mycotoxins including deoxynivalenol (DON) which are toxic to human and animals. This disease has resulted in the serious losses in grain yield and quality. We established through a first bibliographic review that during off season fungus survives saprophytically on the crop residues (ecological habitat) and serves as primary inoculum for the next season crop. However, we noticed also that the literature was poor about the role mycotoxins could play in the establishment of F. graminearum in such a habitat. The main aim of this thesis was therefore to test whether the presence of mycotoxins in the crop residues gives an advantage to F. graminearum to survive and develop a primary inoculum in the presence of the whole soil biota including fungi, bacteria, protozoa, nematodes and earthworms. We studied the impact of DON on the soil communities in the field as well as in microcosms, in wheat as well as in maize residues under tillage and no-tillage conditions. The disease development and the yield were noted in the field experiment. Some DON resistant active fungal decomposers and nitrogen fixing bacteria were picked and the dynamics of F. graminearum was observed by accelerating decomposition of crop residue in their presence, in the presence or absence of DON.During this study, the dynamic and survival of F. graminearum and total fungal and bacterial communities were examined by using quantitative real time polymerase chain reaction (qPCR) as well as by plate counting. At the same time, the structures of microbial communities were determined by using terminal restriction fragment length polymorphism analysis (T-RFLP). The DON resistance of isolated fungal decomposers and nitrogen fixers was tested by using minimal inhibitory concentration test (MIC). Nematodes and earthworms were quantified through binocular observations. The fate of DON was determined by quantifying the mycotoxin by high performance liquid chromatography (HPLC).The results suggested that DON in crop residues showed an impact on the biotic components of the soil but the impact depended on the communities and on the location of the residues (on surface or incorporated in the soil). The molecular biomass shows that the fungal and bacterial densities were significantly affected by the presence of DON. The presence of DON played significant role on the structure of bacterial and protozoan community while the nematodes and fungal communities remained unaffected. MIC results showed that the susceptibility of some competitive fungal strains towards DON was dependent on the dose of mycotoxin. The earthworms (Lumbricus terrestris) were not affected by the presence of mycotoxin. The degradation of DON in the residues was dependent on the time, the location of residues and the soil biota. The quantification of F. graminearum suggested that the presence of DON gave no advantage in the survival and development of primary inoculum during the decomposition of crop residues in the soil. We conclude that fungal decomposers can be selected on their enzymatic potential towards organic matter more than on the DON resistance to increase the degradation of the straw left at the surface and limit the subsequent development of F. graminearum
Exploration pangénomique des anomalies du développement de causes rares by Sophie Nambot( )

2 editions published in 2019 in French and held by 2 WorldCat member libraries worldwide

Titre : Exploration pangénomique des anomalies du développement de causes raresMots clés : anomalies du développement, séquençage d'exome, paratage de données, phénotypage inverseLes anomalies du développement sont un groupe de maladies hétérogènes, tant sur le plan clinique que moléculaire. Elles comprennent plus de 3.000 maladies monogéniques, mais seulement un tiers d'entre elles ont actuellement une cause moléculaire connue. Bien que les progrès des techniques de séquençage aient permis d'identifier des centaines de nouveaux gènes ces dernières années, de nombreux patients restent encore sans diagnostic. La grande hétérogénéité génétique de ces pathologies met à l'épreuve la démarche diagnostique classique comprenant une expertise clinique, une étude pan-génomique par puce à ADN et/ou l'analyse ciblée de gènes connus et, depuis peu, le séquençage haut débit d'exome ciblé sur les gènes associés à une pathologie humaine. En attendant que le séquençage du génome soit économiquement plus accessible et l'interprétaion des ses données mieux appréhendée pour une utilisation diagnostique, nous avons choisi d'explorer de nouvelles stratégies afin d'optimiser le séquençage d'exome dans l'identification de nouvelles bases moléculaires.Le premier article a pour objectif de démontrer la faisabilité et l'efficacité de la réanalyse annuelle des données de séquençage d'exome négatif dans un cadre diagnostique. Les patients éligibles à l'étude présentaient une anomalie du développement sans cause moléculaire établie après une démarche diagnostique classique incluant une analyse chromosomique sur puce à ADN et une analyse d'exome diagnostique. Cette première étude a permis de réaliser un nombre significatif de diagnostics supplémentaires, mais aussi d'identifier des variations candidates pour lesquelles nous avons utilisé le partage international de données et l'approche de phénotypage inverse pour établir des corrélations phénotype-génotype et des cohortes de réplication génotypique et/ou phénotypique. Ces stratégies nous ont permis de remplir les critères ACMG nécessaires pour établir la pathogénicité de ces variations.Fort de cette expérience et souhaitant aller plus loin dans l'identification de nouvelles bases moléculaires pour nos patients, nous avons poursuivi cet effort de réanalyse dans un cadre de recherche. Ce travail fait l'objet du second article de cette thèse et a conduit à l'identification de 17 nouveaux gènes d'anomalies du développement. Le partage de données a conduit à l'élaboration de nombreuses collaborations internationales et de plusieurs études fonctionnelles par des équipes spécialisées.L'application de ces outils dans une forme syndromique de déficience intellectuelle ultra-rare est illustrée à travers le troisieme article. Suite à un effort collaboratif important, nous avons pu décrire de manière précise le phénotype de 25 patients jamais rapportés dans la littérature porteurs de variations pathogènes au sein du gène TBR1, gène candidat dans les troubles du spectre autistique associés à une déficience intellectuelle.Ces différents travaux démontrent l'efficacité de stratégies innovantes dans l'identification de nouvelles bases moléculaires chez les patients atteints d'anomalies du développement, à savoir la réanalyse des données d'exome, le phénotypage inverse et le partage international de données. Pour les patients et leur famille, cela permet de comprendre l'origine de leur pathologie, de mettre fin à l'errance diagnostique, de préciser le pronostic et l'évolution développementale probable, et la mise en place d'une prise en charge adaptés. Il est aussi indispensable pour fournir un conseil génétique fiable, et éventuellement proposer un diagnostic prénatal voire pré-implantatoire. Pour les généticiens, cela permet la compréhension de nouveaux processus physiopathologiques, l'élaboration de nouveaux tests diagnostiques et la découverte de nouvelles cibles thérapeutiques
Etude de l'influence de la leptine sur les mécanismes cellulaires de la mise en route du travail dans un modèle d'accouchement prématuré : approches pharmacologiques by Marina Barrichon( Book )

2 editions published in 2015 in French and held by 2 WorldCat member libraries worldwide

Maternal obesity is associated with a wide spectrum of adverse pregnancy outcomes leading to higher rates of postdate pregnancies or preterm deliveries. Finding new strategies for the management of the Threat of Preterm Labor (TPL) is an important Public Health issue. Indeed, the only available strategy (tocolytic drugs) inhibiting uterine contractions, does not allow delaying parturition for more than 48 hours. The physio-pathological mechanisms leading to TPL remain poorly understood, but it has been shown that labor onset is associated with a phenotypic switch of myometrial smooth muscle cell from a proliferative to a contractile phenotype. In this work, we investigated the effect of leptin, an adipokine synthesized by the placenta during pregnancy and that has been proposed for the management of preterm labor, as it is able to prevent in vitro uterine contractility, on human myometrial cell proliferation and differentiation. In this work, we demonstrated that leptin induces myometrial proliferation, with or without the induction of pro-inflammatory signaling. Indeed, we highlight that leptin at 50ng/ml is able to activate IL-6R/NFkB pro-inflammatory pathway described to play a role in the onset of labor while leptin at 6.25 ng/ml stimulates OB-R/ERK1/2 signaling pathway, leading to proliferation. In addition, preliminary results on cell differentiation have suggested that leptin at 6.25ng/ml is able to oppose this transition, whereas leptin at 50ng/ml induces cytoskeletal reorganization, COX2 and Cx43 protein expression and increased calcium influx, leading to effective myometrial contractions. Finally, this work emphasizes the potential value of leptin in the pharmacological management of TPL and it also strengthens the hypothesis that leptin might be a contributory factor in the delivery disorders observed in obese women
Transfert des éléments traces métalliques vers les végétaux : mécanismes et évaluations des risques dans des environnements exposés à des activités anthropiques by Mohamad Assad( )

2 editions published in 2017 in French and held by 2 WorldCat member libraries worldwide

Metal trace element (HME) -free residues from industrial activities represent a potential risk of environmental pollution. These tailings dumps require a stabilization of the ETMs to limit their dispersion by air, soil, and streams, and ultimately their transport to initially uncontaminated areas. This stabilization can be achieved by adequate plant cover. This thesis work focused on 3 experimental sites, which have as common point to be contaminated sediment storage areas or industrial effluents loaded with ETMs. The general objective of this thesis work was to study the transfer and storage modes of ETMs to the aerial parts of plants grown on soils from these experimental sites. The first objective concerned a discharge of effluents (Inovyn), resulting from the electrolytic activity of the Solvay (Tavaux) plant and enriched in Hg. The Hg, because of its low boiling point, is easily transferred from the sediments to the atmosphere in the form of volatile compounds. Thus, the vegetal cover of this lagoon is exposed by its aerial biomass to the volatile compounds of Hg, but also by the rhizosphere to the Hg compounds present in the substrate. In this work, several plant species of the Salicaceae family (poplar) and Solanaceae (pepper, tomato, aubergine, and tobacco) were exposed to Hg in pot experiments, with simple exposure to a Hg-enriched atmosphere. , or double exposure to Hg-enriched soil and atmosphere. In all cases, transfer of Hg into the leaves occurs only by air, and accumulation increases significantly with leaf age. We also found that the Hg content of the Solanaceae fruit was about 100 times lower than that of the leaves, thus limiting the risk of exposure to Hg through their consumption. We have also shown that a small proportion (7%) of the Hg is in the form of methylHg in poplar leaves, and that 16 to 26% of the Hg accumulated in pepper or poplar leaves were bound to soluble proteins. The second objective concerns the Thann (Cristal) and Fresnes sur Escaut (VNF) sites, for which we have studied the transfer of ETMs to vegetable species, in order to mimic the impact of these contaminants on vegetable garden crops. Poplar has also been used as a reference species. The amounts of fresh mass of the edible parts to be ingested to reach the daily dose were calculated for each MTE. Only Cd (Fresnes) and Cr (Thann) presented a potential risk, since they accumulate in the consumable parts of these plants at high levels. It should be noted, however, that these experiments were conducted in scenarios where exposure conditions were maximized. The transfer of ETMs (including Cd and Zn) to poplar has confirmed previous studies, highlighting the importance of appropriate management of the biomass produced at such sites. From an ecological point of view, the work of this thesis confirms the importance and the necessity of the revegetation of the sites contaminated by ETMs in order to limit the dispersion of the dust, and consequently the ETMs around. From a health point of view, the work emphasizes the importance of estimating the specific risk related to the ingestion of vegetable species of interest regularly grown by the inhabitants around the sites potentially emitting ETMs, generating a link between species and accumulated ETMs. This work therefore provides a number of elements for understanding the fate of ETMs and in particular the Hg in the soil / plant system and the risks associated with the ingestion of the edible parts of potentially contaminated cultivated plants
Rôle des acides aminés dans la production d'amines biogènes chez Oenococcus oeni by Said Dandach( Book )

2 editions published in 2013 in French and held by 2 WorldCat member libraries worldwide

In wine biogenic amines (BA) are mainly of microbial origin, Oenococcus oeni, the mainresponsible for malolactic fermentation, has been identified as a BA producer from nitrogenprecursors. Oenococcus oeni possess numerous amino acid auxotrophies that are precursors ofbiogenic amines. No study has been done so far to look at the relationship betweenauxotrophy for amino acids precursors of BA and the level of BA in the medium. In order todo so, 80 Oenococcus oeni strains were isolated from red wines. The detection of genesencoding the different decarboxylases responsible for BA synthesis has been realised. Inparallel, the auxotrophy for the four amino acids (Arg, Tyr, His, Phe) precursors of BA hascharacterized. Our results demonstrate that there is not direct correlation between auxotrophyand the accumulation of the corresponding BA as well as between the presence ofdecarboxylase gene and the accumulation of the corresponding BA. High levels of agmatineproduced from arginine decarboxylation by Oenococcus oeni is reported for the first time.Agmatine production is strain dependant. the most adapted to acidic environment is the strainwhith use arginine in higher level with same proportion for ADI pathway and argininedecarboxylase. Agmatine addition in wines reduce woody aroma probably by formation ofsciff bases between aromla compounds and amine
Protéome salivaire et sensibilité à l'amertume chez l'Homme by Micheline Dsamou( Book )

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

Bitterness is present in every day beverages (e.g. coffee) and foods (e.g. vegetables such as cruciferous plants). However, bitterness is perceived differently among individuals and some foods considered as healthy may be rejected due to their bitter taste. Several genetic (eg. genetic polymorphism of bitter taste receptors) or environmental (eg. age, medications) factors partly explain the interindividual variability in bitterness perception. However, other peri-receptor factors may intervene, in particular salivary composition. First, in order to investigate the link between salivary proteome and sensitivity to bitterness, the detection threshold to the bitter taste of caffeine was measured in 29 male healthy subjects. Their resting saliva was studied by one- and two-dimensional electrophoresis. Two-dimensional electrophoresis revealed that 26 out of 255 spots were significantly different between the 6 hypersensitive and 6 hyposensitive subjects to the bitter taste of caffeine. Identification of the 26 spots revealed an overexpression of amylase-, serum albumin-, and immunoglobulin A fragments, and an underexpression of cystatin SN in hypersensitive subjects. The latter finding was confirmed by Western blotting. These results have led to formulate an hypothesis on the role of in-mouth proteolysis in bitterness perception. Second, in order to study the effect of bitter molecules on salivary composition, an in vitro study was performed on undifferentiated and differentiated human salivary cell line HSG. After setting the experimental conditions for HSG cell differentiation (culture in 3D conditions), cystatin SN was detected in HSG cells by Western blot after treatment with caffeine, quinine, and urea. After cell exposure with caffeine at 5, 50 and 100 µM, quantification by ELISA demonstrated that cystatin SN was always more abundant in differentiated vs undifferentiated HSG cells. Specifically in differentiated cells, caffeine exposure resulted in over-expression of cystatin SN, 50µM inducing the highest effect. Cystatin SN was also detected in culture media of the HSG cells
Etude du rôle des protéines QSOX1 et GABARAPL1 dans l'autophagie et le cancer by Laura Poillet Perez( )

2 editions published in 2015 in French and held by 2 WorldCat member libraries worldwide

The aim of my thesis was to study the role of QSOX1 and GABARAPL1 (GL1) in autophagy and cancer. QSOX1 protein has been shown to be involved in the regulation of protein folding and is associated with protection against cellular stress and cancer. Given the function of QSOX1 in stress and cancer, two processes which have been previously linked to autophagy, we have studied the role of QSOX1 in autophagy. We showed that QSOX1 protein can maintain cellular homeostasis during amino acids starvation. Our results also indicated that QSOX1 inhibits autophagy through the inhibition of autophagosome/lysosome fusion which could explain the role of QSOX1 on cell invasion. The GL1 protein, belonging to the ATG8 family and GABARAP subfamily, is associated with autophagosomes during autophagy and have a tumor suppressor role. Given the function of GL1 in cancer and autophagy, we aimed to characterize the role of GL1 in autophagy and determine whether GL1 conjugation to autophagosomes is necessary for its tumor suppressive functions. Our results demonstrated that GL1 presents different regulatory functions during early and later stages of autophagy. Sorne of these functions seem to be independent of its conjugation to autophagosomes. Interestingly, GLl tumor suppressive function appeared independent of its conjugation to autophagosomes. Our results also demonstrated that GL1 play an important role in the regulation of metabolism and mitochondrial homeostasis through autophagy, function which could explain its role in cancer. Together, this work allowed us to establish a link between autophagy, cellular stress, metabolism and cancer
Ciblage de l'inflammation cutanée par les nanoparticules polymériques by Céline Try( )

2 editions published in 2015 in French and held by 2 WorldCat member libraries worldwide

For several years now, nanocarriers have been considered as the most promising strategy to improve skin penetration of active ingredients. Moreover, these carriers are more efficient at targeting and controlling drug release into the skin, which leads to increased treatment efficiency and reduced side effects. Polymeric nanoparticles have been the object of an increasing number of studies due to their good physicochemical stability and prolonged release of active ingredients which is superior to any other carriers. Recently, the Laboratory of Pharmaceutical Engineering at Besançon proved in vivo, that polymeric nanoparticles with a diameter smaller or equivalent to I 00 nm specifically penetrated in inflamed skin of mice whilst no penetration was observed in healthy skin. The first aim ofthis thesis was to confirm this hypothesis on another animal's inflamed skin, in instance the pig. Our results confirm the poor penetration of polymeric nanoparticles in healthy skin ofpigs and show various degree ofpenetration depending on the size of the nanoparticles into the inflamed skin area. The second objective ofthis work was to evaluate the skin penetration of our polymeric nanoparticles in humans. A proof of concept has been developed in the Department of Dermatology at Besancon University Hospital. The first results ofthis clinical trial tend to confim1 the greater penetration ofour carrier, specifically in inflamed skin. In fact, no penetration of polymeric nanoparticles with a size close to 100 nm was observed in healthy skin ofvolunteers or in the non-inflamed skin of patients suffering from atopic dennatitis. Conversely, a high penetration ofthese carriers was observed in the skin lesions of patients with atopic dermatitis. If the results ofthis clinical trial are confirmed, we plan to load an anti-inflammatory or an immunosuppressive drug into the nanoparticles to evaluate the therapeutic value ofthese nanocarriers in human medicine in the treatment ofatopic dermatitis. Meanwhile, a similar study may be undertaken in veterinary medicine for the treatment of atopic dermatitis in dogs which is a common disease whose current treatment is based on the oral administration of corticosteroids and cause many undesirable side effects
Marqueurs du métabolisme du fer et dérivés de la L-arginine dans la cardiopathie ischémique : mise en évidence, intérêt de leur évaluation et rôle du stress oxydant en phase aiguë d'infarctus du myocarde by Aurélie Gudjoncik( )

2 editions published in 2015 in French and held by 2 WorldCat member libraries worldwide

Myocardial infarction (MI) is mostly caused by complications of atherosclerosis, whose the development would be initiated by a dysfunction of the vascular endothelium, characterized by an inflammatory condition and oxidative stress.In this pathogenesis, iron interacts at different levels and also has a major role in the development of endothelial dysfunction. Hepcidin and erythroferrone (discovered earlier as the myonectin/CTRP 15) participate in a major way in regulating certain stages of iron metabolism.Asymmetric dimethylarginine (ADMA), a marker of endothelial dysfunction is associated with most cardiovascular risk factors. Symmetrical dimethyl-arginine (SDMA), its stereoisomer, has an exclusively renal elimination and is considered as a powerful renal function marker.We aimed to study, in patients with acute MI, the meaning of the "traditional" status iron parameters, two proteins involved in the regulation of iron, hepcidin and myonectin, as well as the two L-arginine derivatives, ADMA and SDMA. In our first prospective study, we observe that, in patients with acute MI, the values of SDMA, and only weakly ADMA, are associated with admission blood glucose, beyond traditional dimethylarginine determinants and may therefore have biological activity beyond renal function.Our second work suggests that patients with heart failure in the acute phase of MI present more frequently anemia and a certain degree of iron deficiency. New iron metabolism regulators biomarkers, hepcidin and myonectin showed a trend toward an increase in the serum levels in these patients characterized by an increase in CRP.Thus, our work suggests the links between these new regulators of iron metabolism in acute MI with functional consequences of cardiovascular diseases, particularly in terms of anemia and heart failure
Implication de la plasticité cérébrale hypothalamique dans la régulation de l'homéostasie énergétique chez la souris : effet d'un régime gras by Alexandra Gouazé( Book )

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

The hypothalamus plays a crucial role in the control of energy balance. In adult brain, this area remain plastic and the cellular network can be rapidly modified under environmental pressures. Studies show than hypothalamic remodeling are disturbed when metabolic diseases such as obesity or type II diabetes are declared. In this study we hypothesized that a high fat diet (HFD) inducing obesity could rapidly causes cell modifications in the adult hypothalamus network. To answer this question, we have established a one week HFD mouse model, and evaluated to type of hypothalamic plasticity which are synaptic plasticity and neurogenesis. Our results show that HFD leads to an increase of the excitatory pre-synaptic tonus on the POMC neurons. This phenomenon implies polysialisation of the adhesion protein NCAM. We also demonstated than this rapid rewiring is reinforced by the increase of cell renewal, and more specifically by an increase of cell proliferation. Blockade of proliferation with the anti-mitotic araC prevent food intake regulation observed in control mice and accelerate the onset of obesity. These results suggest that neoformed cells are crucial for the maintenance of energy balance. In fact, new cells mainly differenciate into neurons, and the proportion of new POMC neurones of the arcuate nucleus (ARC) is twice the one of mice under standard diet (STD). HFD directs maturation of new neurons toward anorexigenic phenotype. Our experiments demonstrate than the hypothalamus rapidly remodels after an energy imbalance, and establish a succession of changes leading to a rapid restablishment of energy homeostasis
Caractérisation fonctionnelle de la protéine GABARAPL1 par identification de nouveaux partenaires protéiques et étude de l'expression de gabarapll dans les cancers du sein by Stéphanie Seguin-Py( )

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

The GABARAPL1 (GABARAP like 1) protein, also named GECl (Glandular Epithelial Cell 1), displays a high percentage of identity with the GABARAP (GABAA Receptor-Associated Protein), GATE-16 (Golgi-Associated A TPase Enhancer of 16 kDa) and Atg8 (Autophagy-related 8) proteins, and a lesser identity with LC3 (Light Chain 3) family of proteins. The GABARAPL1 protein is expressed in ail tissues, predominantly in the central nervous system and is involved in intracellular transport of GABAA receptors (Gamma-AminoButyric Acid type A receptor) and KOR (K Opioid Receptor). In addition, a Iow expression of the gabarap1 gene was shown in various cancer cell lines, suggesting its involvement in the genesis and/or progression oftumors. The search for GABARAPL 1 prote in partners has Ied to the identification of different proteins. The interaction between GABARAPL1 and the protein partner: HSP90 (Heat Shock Protein 90) was studied in rat brain and MCF-7 cells, in which we showed that HSP90 protects GABARAPL1 from degradation by the proteasome. Additionally, it was established that during autophagy, GABARAPL1 is cleaved to its mature form and conjugated to phospholipids. lt then co-localizes partially with lysosomes and autophagosomes. We also demonstrated that gabarap!J is weakly expressed in breast tumor tissues and that overexpression of the FLAGGABARAPL1-6HIS recombinant protein in MCF-7 cells significantly reduces their growth. Finally, a strong expression of gabarap1 is correlated with increased survival of patients with lymph node-positive breast cancer
Influence de traitements de réticulation sans solvant sur les propriétés de films à base de gélatine et chitosan encapsulant ou non des antioxydants naturels : caractérisations physico-chimiques et application by Nasreddine Benbettaieb( Book )

2 editions published in 2015 in French and held by 2 WorldCat member libraries worldwide

Ce travail de thèse a pour objectif de formuler un emballage comestible à base d'un mélange de chitosan et de gélatine (bœuf ou poisson), de mieux comprendre l'influence d'irradiations par faisceaux d'électrons et de l'incorporation d'antioxydants naturels sur les propriétés physico-chimiques et fonctionnelles des films. Une étude de l'effet de l'irradiation sur la cinétique de libération des antioxydants dans un milieu liquide simple a été étudiée pour validation. Une étude préliminaire a montré d'abord que la densification de la solution filmogène puis du gel pendant le séchage ne dépend ni de l'épaisseur, ni de la concentration, ni du temps et laisse supposer une diffusion Fickienne de l'eau dans la matrice. La perméabilité à la vapeur d'eau augmente linéairement avec l'épaisseur de films et d'autant plus lorsque l'étendue du différentiel d'humidités relatives est élevé. Ce phénomène est attribué à un mécanisme de gonflement et de plastification du réseau de gélatine-chitosan par l'eau. L'effet du taux de mélange de deux biopolymères a montré une amélioration des propriétés mécaniques et barrières à l'eau et à l'oxygène des films de chitosan. Ces gains de performances sont dus à la bonne miscibilité des deux macromolécules et aux interactions moléculaires établies suite à la formation d'un complexe polyélectrolytique, confirmé par analyse FTIR. L'irradiation des films après séchage accroit la polarité de surface et l'hydrophilie des films et ainsi induit une augmentation des propriétés barrières à la vapeur d'eau et à l'oxygène, mais aussi des mécaniques et thermiques des films. Toutefois, l'irradiation ne modifie pas la cristallinité des films. L'incorporation des antioxydants (acide férulique, coumarine, quercétine et tyrosol) avec ou sans irradiation agit différemment, selon leur nature, sur l'organisation du réseau macromoléculaire et donc sur les propriétés des films. Ainsi, l'acide férulique et le tyrosol réduise la perméabilité à la vapeur d'eau mesurée à un gradient de 0-30% d'humidité relative, alors qu'ils l'augmentent jusqu'à 90 fois avec un gradient 30-84% et un traitement d'irradiation. La perméabilité à l'oxygène diminue d'une façon significative après ajout de quercétine ou de tyrosol et après irradiation. L'acide férulique et la coumarine augmente la force à la rupture des films alors que ce sont la quercétine et l'acide férulique qui permettent d'accroitre la résistance thermique des films. Ces résultats mettent ainsi en évidence la complexité des interactions mises en jeu entre les antioxydants et les chaînes de chitosan et/ou de gélatine, leur dépendance au niveau d'hydratation du système et à l'impact du traitement de réticulation par irradiation. Il faut noter que l'irradiation a permis de protéger les molécules actives contre l'oxydation durant une longue période de stockage des films. La libération en milieu aqueux de l'acide férulique est la plus ralentie avec une rétention dans les films la plus élevée à l'équilibre (27%). Les coefficients de diffusion des antioxydants, déterminés à partir des cinétiques de libération ont pu être modulés (50%) grâce à l'irradiation
Etude de deux modalités de phytomanagement testées sur un terrain de gestion de sédiments contaminés par des métaux et métalloïdes by Phonethip Phanthavongsa( Book )

2 editions published in 2018 in French and held by 2 WorldCat member libraries worldwide

Phytomanagement is an emerging approach that includes plant biomass valorization for the management of polluted soils and sites. To evaluate the long-term performance of this strategy at field scale, two phytomanaged sites of 1 ha each (sites A and B) were implanted in Fresnes-sur-Escaut (Hauts-de-France) in 2011/2012 at a dredged-sediment disposal site contaminated with potentially toxic elements or PTE (Cd, Cu, Pb et Zn). The thesis work is based on the study of the two sites with the following objectives: (1) study the dynamics of selected plants (Deschampsia cespitosa, Skado and I-214 poplars, Tordis and Inger willows), colonizing plants and invaders, (2) study the efficiency of amendments (mycorrhizal fungi inoculum, basic mineral amendment) on sediment PTE mobility, on aerial plant parts PTE accumulation and on the microbial diversity in soils and tree roots.The efficiency of the grass D. cespitosa for phytomanagement at the site B has been highlighted. The plant was tolerant to the site conditions, had low concentrations of Cd, Cu and Pb in shoots and formed a dense and perennial plant cover. At the site A, the herbaceous plant cover formed by plant colonists was heterogenous with a dominance of the species Urtica dioïca.In amended and non-amended plots, U. dioïca showed higher concentrations of Cd, Cu, Pb and Zn than the same plants from uncontaminated soils. According to risk calculations based on Cd and Zn concentrations, there was no risk related to the ingestion of these herbaceous plants by herbivorous animals. Concerning poplars and willows dedicated to energy production, high Cd and Zn concentrations were found in their leaves regardless of the amendments. These leaves may pose a risk for herbivorous animals. Unlike poplars which were very tolerant to the site conditions, willows showed a reduction of growth and survival rate in the amended and non-amended plots sown with D. cespitosa, because of belowground competition with D. cespitosa. Ecotoxicological tests revealed that soil phytotoxicity was also responsible of the willow growth reduction. Besides, the biological and chemical amendments had no significant effect on PTE mobility and speciation in soils after 4 or 5 years of phytomanagement. Their effects on PTE transfers in plants varied depending on the species, levels of pollution and time. The study of microbial communities in tree roots revealed that the herbaceous cover and soil pollution had a significant impact on microbial composition whereas the amendments did not affect the microbial communities
A contribution of understanding the stability of commercial PLA films for food packaging and its surface modifications by Jeancarlo Renzo Rocca Smith( )

2 editions published in 2017 in English and held by 2 WorldCat member libraries worldwide

I materiali plastici convenzionali trovano impiego in tutti campi della nostra vita, specialmente nel settore del packaging alimentare, ed in seguito all'utilizzo contaminano e danneggiano il nostro ecosistema. Materiali plastici derivanti da risorse naturali e biodegradabili, come acido polilattico (PLA), sono attualmente disponibili sul mercato anche se caratterizzati da performances inferiori.Questo progetto di dottorato è mirato 1) allo studio della stabilità di film di PLA a varie condizioni di stoccaggio come temperatura, umidità relativa, pH, o esposizione a vapori o gas; 2) a comprendere meglio le influenze di alcuni processi industriali come trattamento corona e hot press nelle proprietà dei film di PLA; 3) a sviluppare complessi multistrato tra film di PLA e di glutine che abbiano proprietà barriera più elevate rispetto ai singoli film.Gli imballaggi a base di PLA sono stati prodotti da Taghleef Industries, produttore leader nel settore e dotato di infrastrutture atte ai trattamenti di modificazione di superfice come il trattamento corona. I film a base di glutine e i coatings sono stati sviluppati e ottimizzati su scala di laboratorio, così come i complessi trilaminari PLA-glutine-PLA.Le proprietà fisiche e chimiche dei film di PLA sono state investigate a livello di superficie, così come a livello di bulk. Diverse tecniche analitiche, provenienti dal campo delle scienze dei materiali e delle scienze degli alimenti, sono state adottate in questo progetto di dottorato come calorimetria differenziale a scansione (DSC), termogravimetria (TGA), cromatografia di esclusione molecolare (SEC), microscopia a forza atomica (AFM), microscopia elettronica a scansione (SEM), spettrofotometria infrarossa a trasformata di Fourier in riflettanza totale attenuata (ATR-FTIR) e spettroscopia fotoelettronica a raggi X (XPS).Le proprietà funzionali come le permeabilità al vapore acqueo (H2O), all'ossigeno (O2), al diossido di carbonio (CO2) o all'elio (He) sono state investigate, cosi come l'assorbimento di gas e/o vapori, le proprietà meccaniche e le proprietà di superfice.Nonostante i film di PLA assorbano linearmente CO2 a pressioni crescenti, l'assorbimento di tale gas è ridotto a basse pressioni in modo da non modificare le sue proprietà fisiche - come contrariamente osservato quando il PLA è esposto a CO2 ad alte pressioni - e da non influenzare negativamente il suo utilizzo come imballaggio alimentare. Ad ogni modo, quando i film di PLA sono esposti ad ambienti umidi, o quando sono immersi in acqua liquida, sono significativamente degradati per idrolisi dopo due mesi di stoccaggio a 50 °C (test accelerato). Questo deterioramento chimico è stato evidenziato da una significativa riduzione del peso molecolare del PLA che, conseguentemente, induce una sua perdita di trasparenza e ne incrementa la sua cristallinità. Inoltre, è stato evidenziato che il pH non influenza la velocità di idrolisi. Quest'informazione ha importanza pratica per possibili utilizzi di PLA come imballaggio di alimenti ad alta umidità.Il glutine è stato scelto per le sue alte proprietà barriera, quando è protetto da ambienti ad alta umidità. Si è visto che l'incorporazione di lipidi non porta con sé grandi miglioramenti nelle performances dei film a base di glutine. Invece, l'utilizzo della tecnologia di omogeneizzazione ad alte pressioni permette una migliore dispersione del glutine, ottenendo film più omogenei e con migliori proprietà funzionali. Questa tecnologia è stata quindi scelta per produrre i complessi multistrato, intercalando i film di glutine tra due film di PLA, usando il trattamento hot press (10 MPa, 130 °C, 10 min). Si è osservato che il trattamento hot press modifica le proprietà dei film di PLA, di glutine e dei film multistrato Hot press induce cristallizzazione in PLA, e conseguentemente aumenta le sue proprietà barriera complessive, approssimativamente al 40 % all'acqua e al 60 % all'ossigeno (...)
Propagation de la rupture sismique dans la lithosphère océanique : l'exemple de la Corse : une étude basée sur l'analyse structurale des cataclasites et pseudotachylytes jalonnant les failles dans les roches mafiques et ultramafiques accrétées ou obductées sur les continents by Remi Magott( )

2 editions published in 2016 in French and held by 2 WorldCat member libraries worldwide

De par leurs magnitudes élevées et leur potentiel tsunamigénique, les séismes qui se produisent en contexte de subduction présentent un risque majeur pour les villes côtières souvent densément peuplées. La compréhension de la géométrie et du fonctionnement des zones de failles associées à ces ruptures sismiques a donc fait l'objet de nombreuses recherches sismologiques et géologiques.L'objectif de cette thèse est centré sur la caractérisation des zones de failles paléo-sismiques traversant des formations ophiolitiques subductées puis exhumées en surface des continent et sur leur comparaison avec les zones sismogéniques actuelles. Elle s'appuie sur une approche multi-échelle faisant intervenir les outils de la géologie structurale, de la pétrographie microstructurale, de la minéralogie, de la géochimie ainsi que les données de la géophysique. Le cas de la Corse alpine, de par la présence de nombreuses pseudotachylytes (étant considérées comme des fossiles de séismes) mafiques et ultramafiques constitue un cas d'étude idéal.La rupture sismique dans la nappe du Cima di Gratera est matérialisée par des réseaux de pseudotachylytes parallèles ou à fort pendages situées de part et d'autre de la discontinuité tectonique séparant les unités ultramafiques et mafiques formant la nappe. Le système de faille est caractérisé par une cinématique vers l'ouest associée à la subduction de la plaque océanique liguro-piémontaise sous la plaque adriatique. Les analyses minéralogiques des microlites présentes dans les pseudotachylytes mafiques indiquent une formation des veines en contexte de pression et température du facies eclogite, correspondant à une profondeur comprise entre 60 et 70 km, soit le début de la zone de sismicité dite de profondeur intermédiaire. La géométrie du système de faille a également pu être comparée à des géométries observées via la géophysique au large du nord-est Japon et à des profondeurs similaires.A également été mis en lumière l'impact de la serpentinisation sur le caractère sismique / asismique des discontinuités tectoniques faisant intervenir des formations mafiques et ultramafiques. En effet, la fusion frictionnelle issue des ruptures sismiques et responsable de la formation des veines de pseudotachylytes n'a été observée que dans le cas où était mis en contact la péridotite fraiche ou faiblement serpentinisée et le métagabbro. Les contacts impliquant la serpentinite et le métagabbro n'en présentent jamais et peuvent donc être considérés comme asismiques. Au regard de l'épaisseur des réseaux de pseudotachylytes dans les masses de péridotite et de leur absence dans les serpentinites, les masses de péridotites peuvent donc être assimilées à des aspérités au sein même de la plaque plongeante
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École doctorale Environnements, Santé (Dijon ; Besançon ; Belfort)

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