ED Sciences Chimiques
Tailoring of the internal surface of PEGylated nanoparticles to modulate the biological identity of the protein corona towards macrophages in the atheroma plaque
by Henri COSTE (ICMCB - Institut de Chimie de la Matière Condensée de Bordeaux)
The defense will take place at 14h00 - Amphithéâtre de l'ICMCB 87 Avenue du Dr Albert Schweitzer 33600 Pessac
in front of the jury composed of
- Damien MERTZ - Directeur de recherche - Université de Strasbourg - Rapporteur
- Kawthar BOUCHEMAL - Professeure des universités - Chimie ParisTech-PSL - Rapporteur
- Elisabeth GARANGER - Directrice de recherche - Université de Bordeaux - Examinateur
- Cyril AYMONIER - Directeur de recherche - Université de Bordeaux - Examinateur
It is clearly established that the protein corona (PC), formed by interaction between plasma proteins and injected nanoparticles (NPs), determines their biological identity, dictating the NPs cell uptake properties, their distribution and fate in vivo. Here, the objective is to study the PC composition related of various surface synthetic identities of superparamagnetic NPs in the context of targeting resident foamy macrophages within vulnerable atherosclerotic plaques. To do so, chemical moieties have been grafted on the inner surface of PEGylated NPs to promote interactions with the Apolipoprotein-A1 (Apo-A1), a protein involved in the cholesterol efflux at the atherosclerotic plaques, while maintaining their colloidal stability in human serum. Covalent chemical surface modifications were applied on maghemite nanoflowers (NFs), morphology known for their remarkable transversal relaxivity values useful for MRI, generating a library of synthetic surface identities. The most promising samples that best interact with the Apo-A1, were selected among the synthetical identities by quantifying the Apo-A1 adsorbed after incubation of the NFs in solution with the protein. These results were comforted by the determination of the affinity constants of the protein for these surface identities measured through fluorescence quenching of the tryptophan residues. Afterwards, their PC formed after incubation in human serum were characterized through tandem mass spectroscopy (LC-MS/MS). An interpretation of the composition of the PC in terms of protein overabundance/depletion has been led in view of the NFs' pharmacokinetics profiles from an in vivo study in mice. Comparative preliminary in vitro fluorescence microscopy studies of the NFs interactions with foamy macrophages models were carried out by incubating the particles in cell culture media and reveal them by indirect immunolabeling. As a perspective, the NFs displaying the best proteomic profiles in terms of opsonin/dysopsonin balance and Apo-A1 abundances to atherosclerosis mice model will be injected to image the plaques by MRI.
Exploring O2 and O6 type lithium-rich layered oxides: structural, electrochemical, and redox insights toward stable high-energy positive electrode material
by Guanlan ZHAO (ICMCB - Institut de Chimie de la Matière Condensée de Bordeaux)
The defense will take place at 9h00 - Amphithéâtre 87 Avenue du Dr Albert Schweitzer, ICMCB, 33600 Pessac, France
in front of the jury composed of
- Marie GUIGNARD - Chargée de recherche - Université de Bordeaux - Directeur de these
- Cyril AYMONIER - Directeur de recherche - CNRS-ICMCB - Examinateur
- Claude DELMAS - Professeur émérite - Université de Bordeaux - CoDirecteur de these
- Marie-Liesse DOUBLET - Directrice de recherche - ICGM - UMR5253 - Examinateur
- Romain BERTHELOT - Chargé de recherche - ICGM - UMR5253 - Rapporteur
- Jean-Noël CHOTARD - Maître de conférences - Laboratoire de Réactivité et Chimie des Solides (LRCS) - Rapporteur
Among the various Li-ion battery chemistries, layered oxides are among the most widely commercialized cathode materials with high capacity. To further push the theoretical capacity, Li-rich compositions have been investigated, as they harness anionic redox in addition to conventional cationic redox. However, the commonly used O3-type layered oxides suffer from severe voltage decay. In this thesis, two alternative stacking types, O2 and O6, are explored as promising candidates to suppress transition-metal migration and mitigate voltage decay. These phases were synthesized via ion-exchange from the P2 parent structure, owing to the metastable nature of the O2 and O6 layered arrangements. The structural and electrochemical properties of these materials are systematically analyzed, with particular emphasis on the role of anionic redox and its influence on structural evolution. Ex situ, in situ, and operando characterizations were employed to probe the cathode behavior during cycling. The results demonstrate that the O2- and O6-type Li-rich layered oxides deliver improved structural integrity and reduced voltage decay over extended cycles. In addition, the machine learning model CHGNet was applied to evaluate the thermodynamic stability and formation preference of O2 versus O6 structures during ion exchange. The results highlight that stacking type could be affected by thermodynamic factors, providing new insights into the design of layered oxides. Overall, this research presents a comprehensive investigation of novel O2- and O6-type Li-rich layered oxides, underlining the potential of alternative stacking sequences to enable stable, high-energy cathode materials for next-generation Li-ion batteries.
ED Entreprise Economie Société
ESTIMATING SUBNATIONAL POPULATIONS IN AFRICAN COUNTRIES USING THE MULTI-REGIONAL METHOD: APPLICATION TO DATA FROM CAMEROON
by Joelle NGOUFO YEMEDI (COMPTRASEC - Centre de Droit Comparé de Travail et de la Sécurité Sociale)
The defense will take place at 10h30 - Salle des Thèses Faculté de droit, Bâtiment C, 16 avenue Léon Duguit, 33608 Pessac Cedex
in front of the jury composed of
- Christophe BERGOUIGNAN - Professeure des universités - Université de Bordeaux - Directeur de these
- Virginie DEJOUX - Professeure des universités - Université de Bourgogne - Examinateur
- Jean-Fraçois LEGER - Maître de conférences - Université Paris 1 - Rapporteur
- Maryse GAIMARD - Professeure émérite - Université de Bourgogne - Rapporteur
Estimating populations is a common practice in demography. It is a matter of estimating the future population of a territory. When population censuses are conducted regularly in a country, population projections are essentially used for forecasting. However, when the intercensal periods are long, as is the case in Africa, population projections can also be used to update population estimations at the national and regional levels, pending a future census. This is the context in which the proposed multiregional method fits in. It makes it possible to produce population estimates at the subnational level while highlighting internal and international migration dynamics, as well as the demographic contribution of a given territory to other territories. By its conception, the multiregional method developed repositions the issue of adjusting imperfect data and the synergy of data from different sources at the heart of projective methods. It also offers the opportunity to decrypt, over a given projection period, the specific contribution of each demographic phenomenon : mortality, fertility, and migration (interregional and international), to the population change in each territory covered by these subnational projections. It thus makes it possible to move away from the assumption of an invariable overall migration balance commonly used in African population projections and to provide users of demographic data with the most realistic population estimates.
Local vs European languages in post-colonial African education systems
by Mathilde COL (BSE - Bordeaux sciences économiques)
The defense will take place at 16h30 - Salle des thèses Bâtiment C 16 Av. Léon Duguit 33600 Pessac
in front of the jury composed of
- Tanguy BERNARD - Professeur des universités - Université de Bordeaux - Directeur de these
- Denis COGNEAU - Directeur de recherche - IRD, Paris School of Economics - CoDirecteur de these
- Paul GLEWWE - Professeur des universités - University of Minnesota - Rapporteur
- Jules GAZEAUD - Chargé de recherche - CNRS, Université Clermont Auvergne - Examinateur
- Elise HUILLERY - Professeure des universités - Université Paris Dauphine - Rapporteur
- Catherine GUIRKINGER - Professeure des universités - University of Namur - Examinateur
The dissertation focuses on improving the quality of education in Sub-Saharan Africa, with particular emphasis on the choice of language of instruction (LoI). The first chapter provides a comprehensive overview of language of instruction policies across all African countries from independence to 2023, as well as their determinants. Using survey and census data, the study analyzes the impact of introducing local languages as LoI instead of the ex-colonial language at the continental level. The second chapter further explores this research question using a quasi-experimental setting in Mali. Exploiting granular data on bilingual education, the analysis finds that using local languages when starting primary education increases literacy in both local languages and French, with no adverse effects on nation-building. The final chapter, co-authored with Luc Behaghel, Simon Briole, and Quentin Daviot, evaluates the impact of a digital technology intervention in a remote region of Senegal through a large-scale RCT. Results indicate limited effects on teachers, but large benefits for student learning when the technology is combined with other education inputs.
ED Sciences de la Vie et de la Santé
Molecular Insights into Pigmentation Defects in Xeroderma Pigmentosum Type C
by Zahraa FAKIH (BoRdeaux Institute of onCology)
The defense will take place at 14h00 - Amphi BBS 2 rue Docteur Hoffman Martinot, Site Carreire, Bâtiment "Bordeaux Biologie Santé" (BBS) 33000, Bordeaux
in front of the jury composed of
- Muriel CARIO - Ingénieure de recherche - Université de Bordeaux, INSERM U1312 - Directeur de these
- Veronique DELMAS - Directeur de recherche - Institut Curie, Orsay, in the unit Signalisation, Radiobiologie et Cancer (UMR-3347 / U1021), team Développement normal et pathologique des mélanocytes. - Rapporteur
- Walid RACHIDI - Professeur - Université Grenoble Alpes; CEA Grenoble; INSERM; IRIG (Institut de Recherche Interdisciplinaire de Grenoble) - Rapporteur
- Sophie JAVERZAT - Professeur - Génétique et Métabolisme (MRGM) research group/laboratory — Rare Diseases, Genetics and Metabolism INSERM U1211 - Examinateur
Xeroderma pigmentosum type C (XP-C) is a rare autosomal recessive disorder caused by defects in the nucleotide excision repair (NER) pathway, characterized by extreme sensitivity to ultraviolet (UV) radiation, early-onset skin cancers, xerosis, and marked pigmentation abnormalities. The clinical manifestations of XP-C primarily result from defective repair of UV-induced DNA lesions, reflecting the essential role of the XPC protein as a key DNA damage recognition factor in global genome NER (GG-NER). However, the molecular mechanisms underlying the pigmentary alterations in XP-C remain poorly understood. This study aimed to elucidate how XPC deficiency contributes to pigmentation abnormalities at the molecular and cellular levels. Skin biopsies from XP-C patients (SPT-I, II) revealed distinct morphological differences between hyperpigmented and hypopigmented regions. Transmission electron microscopy (TEM) demonstrated abundant polymelanosomes in hyperpigmented areas, with melanosomes persisting up to the stratum corneum, whereas hypopigmented regions exhibited a marked reduction in melanosomes and frequent melanocyte detachment or loss, as confirmed by immunofluorescence. Notably, in both hyper- and hypopigmented XP-C skin, keratinocytes displayed polymelanosomes that were larger than those in control skin, although the individual melanosomes within them were smaller. In vitro, primary XPC-knockout (KO) melanocytes exhibited elevated NRF2 levels under basal conditions, followed by NRF2 downregulation and increased reactive oxygen species (ROS) production after a single UVB exposure. Morphological analysis suggested that XPC loss may influence melanocyte dendricity in a phototype-dependent manner: a reduction in dendricity was observed once in XPC KO melanocytes derived from a dark phototype donor, whereas no noticeable morphological changes were detected in melanocytes of light phototypes. However, melanin content and the expression of pigmentation-related markers TYR, TRP1, and PMEL-17 remained comparable to controls, even after acute UVB exposure. Because of dedifferentiation issues observed in primary melanocytes, MNT1 cells were used as a complementary model, in which XPC KO cells showed expression of melanogenesis markers (MITF, DCT, TRP1 and TYR) and melanosome transport players (RAB27A, melanophilin, and myosin Va) comparable to controls, even following chronic UVA/UVB irradiation. Interestingly, preliminary co-culture experiments revealed that XPC KO keratinocytes expressed markedly higher levels of protease-activated receptor-2 (PAR2), a key regulator of melanosome transfer, when co-cultured with either control or XPC KO melanocytes. In parallel, both control and XPC KO melanocytes exhibited elevated RAB27A expression specifically when co-cultured with XPC KO keratinocytes, suggesting that XPC-deficient keratinocytes may secrete factors or present surface cues that enhance melanosome transfer signaling. Collectively, these findings indicate that pigmentation abnormalities in XP-C are not solely attributable to intrinsic melanocyte dysfunction but also involve altered keratinocyte–melanocyte communication. This study further suggests that XPC may play a regulatory role in pigmentation beyond its canonical function in DNA repair. Future work will investigate how chronic UV exposure modulates these interactions to better understand the mechanisms driving pigmentation imbalance in XP-C patients.
Development of a 3D in vitro model to reproduce the osseointegration process of dental implants
by Ghannaa SHAYYA (Bioingénierie tissulaire)
The defense will take place at 14h00 - Module 2.5 Bâtiment CROUS, Campus Carreire, 146 Rue Léo Saignat, 33000 Bordeaux
in front of the jury composed of
- Sylvain CATROS - Professeur des universités - praticien hospitalier - Université de Bordeaux - Directeur de these
- Emmanuel PAUTHE - Professeur des universités - Université de Cergy, Laboratoire ERRMECe - Examinateur
- Alexandra CLOITRE - Maîtresse de conférences - praticienne hospitalière - UFR d'Odontologie, Université de Nantes - Rapporteur
- Christèle COMBES - Professeure - CIRIMAT, INP-ENSIACET Université de Toulouse - Rapporteur
- Liisa KUHN - Professeure - University of Connecticut Health Center - Examinateur
Dental implants have been clinically used for almost 5 decades. The success of dental implant depends on the osseointegration, which is the formation of a structural and functional connection between the bone and dental implant. The significant failure rate of osseointegration on long term requires the development of a convenient research model to better understand this process. Based on a systematic review performed during this thesis, we have observed that 3D in vitro models developed to study dental implant integration are limited in number and lack in-depth biological and mechanical characterization of osseointegration. The objective of this thesis was to develop a novel in vitro model of osseointegration to serve as a platform for biomaterials screening. The first aim was to develop and characterize a mineralized hydrogel-based 3D in vitro model to culture cells with osteogenic differentiation potential. The second aim was to incorporate this hydrogel into 3D-printed porous polylactic acid (PLA) scaffold with dental implants to evaluate their osseointegration. For the hydrogel component of the model, methacrylated collagen (ColMA) 0.2%, methacrylated hyaluronic acid (HAMA) 0.5%, methacrylated gelatine (GelMA) 5% were tested. While GelMA5%, showed compromised cell viability after 5 weeks of culture, and ColMA 0.2% showed high shrinkage, ColMA0.2%+HAMA0.5% showed optimal balance between cell viability and gel stability. For cellular component of the model, three cell candidates were tested: SAOS-2, MC3T3-E1, and immortalized MSCs. SAOS-2 could not attach to the hydrogel while MC3T3-E1 cells and immortalized MSCs had a normal morphology, were metabolically active for 5 weeks and mineralized the gel. Immortalized MSCs were chosen for the model as they are human cells and showed higher mineralization than MC3T3-E1 cells. It was shown that culturing those cells in a culture media with elevated calcium concentration accelerated cell-initiated mineralization. Mineral was deposited in the form of spheres with high calcium and phosphate concentration. Osteoblastic differentiation was also shown through increased ALP gene expression and enzymatic activity. Proteomic profiling revealed a collagen-rich extracellular matrix with enrichment of type I collagen. Additionally, there was enrichment of signalling pathways involved in osteoblastic differentiation. When this hydrogel-based model was further integrated into a 3D-printed PLA scaffold with a dental implant, it was shown that cells could migrate, deposit matrix, and initiate mineralization on the dental implant surface. Additionally, a sensitive pull-out test was specifically developed for the model to detect the attachments initiated by the cells by measuring the force needed to remove the implant from the model. This thesis describes the development of a new 3D in vitro model for dental implant research using a hydrogel-based mineralized bone model that is thoroughly characterized for osteogenic differentiation and mineralization. Additionally, the model was the first to combine 3D-printed polysynthetic scaffold and hydrogel-embedded cells to perform mechanical testing of osseointegration in vitro. The versatility of this model highlights its potential in revolutionizing dental implant screening by overcoming the low complexity of 2D in vitro models and interspecies variability of in vivo models.
Role of 5-HT4 receptors in the modulation of synaptic plasticity within the dentate gyrus
by Soukaina ES-SAFI (Institut de neurosciences cognitives et intégratives d'Aquitaine)
The defense will take place at 9h00 - Amphithéâtre BBS Bâtiment BBS, 2 rue du Dr Hoffmann-Martinot, 33000 Bordeaux
in front of the jury composed of
- Guillaume LUCAS - Chargé de recherche - Université de Bordeaux - Directeur de these
- Abdeslam CHAGRAOUI - Maître de conférences - praticien hospitalier - Université de Rouen - Rapporteur
- Lionel MOULEDOUS - Directeur de recherche - Université de Toulouse - Rapporteur
- Bruno GUIARD - Professeur des universités - Université de Toulouse - Examinateur
- Umberto SPAMPINATO - Professeur émérite - Université de Bordeaux - Examinateur
Current antidepressant drugs (ADs) display limited efficacy and typically require a latency of three to six weeks before clinical improvement is observed. It has been demonstrated that increasing synaptic plasticity within the dentate gyrus (DG) of the hippocampus can induce a rapid and robust antidepressant effect. In this context, serotonin type 4 receptor (5-HT4R) agonists have emerged as promising candidates for the development of fast-acting antidepressants. The aim of this thesis was to investigate the role of 5-HT4Rs in modulating hippocampal synaptic plasticity within the DG. However, 5-HT4R agonists are known to enhance central serotonergic (5-HT) neuronal activity through a “long-loop feedback” originating from the medial prefrontal cortex (mPFC), thereby indirectly stimulating other 5-HT receptor subtypes in the hippocampus, including those expressed in the DG. To dissociate the direct effects of 5-HT4R activation within DG neurons from the indirect effects mediated by the mPFC, we first developed a molecular biology tool based on short hairpin RNA (shRNA) expressed by lentiviral vectors (shRNA-LV), allowing for the inhibition of 5-HT4R expression specifically in the mPFC. This tool was validated using in vivo intracerebral microdialysis, which demonstrated that 5-HT4R stimulation no longer induced an increase in hippocampal 5-HT release in animals injected with the shRNA-LV construct. Next, using in vivo extracellular electrophysiology, we examined the effects of the selective 5-HT4R agonist prucalopride on long-term potentiation (LTP) induced in the DG following high-frequency stimulation (HFS) of the perforant path (PP) in anesthetized rats. LTP was assessed by recording field potentials (FPs) and population spikes (PSs) from granule cells in the DG. Our results show that acute prucalopride treatment in naïve rats reduced the LTP success rate for both FPs and PSs compared to controls, without significantly affecting LTP amplitude. In rats injected with shRNA-LV and acutely treated with prucalopride, this reduction was restored to control levels for both FPs and PSs, again without changes in LTP amplitude. Subchronic (three-day) prucalopride treatment in naïve rats once again reduced the LTP success rate for FPs without altering their amplitude. In contrast, the PS success rate remained similar to that observed after acute treatment, but PS amplitude was significantly and markedly decreased. In shRNA-LV–injected rats receiving the same subchronic treatment, the LTP success rate for FPs was restored, and a trend toward increased FP amplitude was observed compared to controls at the end of the recording period. Taken together, these findings support the involvement of 5-HT4Rs in the modulation of synaptic plasticity within the DG. Activation of these receptors in the mPFC impairs LTP induction, an effect that can be reversed by suppressing their expression. Keywords: Serotonin type 4 receptors, long-term potentiation, rapid-acting antidepressants, medial prefrontal cortex, dentate gyrus, interfering RNA.
BASIS OF NANOSCALE FUNCTION OF NEUROMODULATORY GPCRS INHIBITORY PATHWAYS IN LONG-TERM-DEPRESSION
by Viviana VILLICANA MUNOZ (Institut Interdisciplinaire de Neurosciences)
The defense will take place at 10h30 - Amphi Centre Broca Nouvelle-Aquitaine 146 Rue Léo Saignat, 33076 Bordeaux Cedex
in front of the jury composed of
- Eric HOSY - Directeur de recherche - Université de Bordeaux - Directeur de these
- Sabine LEVI - Directrice de recherche - Universite Paris PSL - Rapporteur
- Pierre TRIFILIEFF - Directeur de recherche - Université de Bordeaux - Examinateur
- Marianne RENNER - Professeure des universités - Sorbonne Université - Rapporteur
- Marianne BENOIT-MARAND - Professeure des universités - Université de Poitiers - Examinateur
- Jérôme BAUFRETON - Directeur de recherche - Université de Bordeaux - Examinateur
Long-term potentiation (LTP) and long-term depression (LTD) are fundamental processes of synaptic plasticity that underlie long-lasting changes in synaptic strength. Together, they form the cellular basis of learning and memory. The balance between these two forms of plasticity is essential during neuronal development, as it refines synaptic connections and enables the emergence of efficient neuronal networks. During critical developmental periods, LTD has been proposed to act as a signal-to-noise filter that enhances circuit efficiency through mechanisms such as synaptic pruning. One of the most prominent forms of LTD at excitatory synapses is mediated by N-methyl-D-aspartate receptors (NMDARs), which recruit intracellular signaling cascades leading to the downregulation of α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptors. Alongside these glutamatergic receptors, excitatory synapses express a variety of highly sensitive G-protein-coupled receptors (GPCRs) that are activated by neuromodulatory inputs in key brain regions such as the hippocampus, where they play a critical role in modulating synaptic plasticity. Understanding how these receptors interact is crucial for elucidating the mechanisms that tune synaptic physiology. In my thesis, I focused on the inhibitory Gi/o-coupled pathway (iGPCRs)—specifically dopaminergic, serotonergic, and histaminergic receptors—to explore the interplay between their intracellular signaling pathways and their potential synergistic interactions with NMDARs in inducing LTD in the hippocampus. First, we established a causal relationship between NMDAR-dependent LTD and synaptic pruning through the chemical induction of LTD, evidenced by electrophysiological and synaptic protein content analyses. Additionally, we characterized the synaptic environments that render connections more susceptible to prune. I then examined whether subthreshold activation of NMDARs, insufficient on its own to induce LTD, could be potentiated through the synergistic activation of inhibitory GPCRs such as the dopaminergic D2 receptor (D2R), serotonergic 5-HT1A receptor, and histaminergic H3 receptor. I found that D2R consistently synergized with NMDARs to restore LTD and promote synaptic pruning, whereas this effect was not observed for the other GPCRs tested. Interestingly, activation of D2R, 5-HT1A, and H3 receptors modified AMPA receptor current kinetics and induced synaptic pruning—effects that were partially reversed by subthreshold NMDAR activation in the serotonergic and histaminergic systems. These findings suggest that non-canonical pathways mediated by GPCR βγ subunits may interact intracellularly with NMDAR signaling. The nanoscale organization of receptors has been shown to be a relevant marker for understanding synaptic transmission. Therefore, in the second part of my research, I employed direct stochastic optical reconstruction microscopy (dSTORM) to investigate the nanoscale organization of D2R. Using a Fab fragment targeting the extracellular loop of D2R, I revealed that the receptors cluster within dendritic spine nanodomains and colocalize with postsynaptic markers. Altogether, these results advance our understanding of the fine neuromodulatory control of LTD and structural plasticity. They highlight dopaminergic receptors as key modulators under conditions of NMDAR hypofunction during neurodevelopment, suggesting that they could represent potential therapeutic targets in neurodevelopmental disorders such as certain forms of autism, where these processes are disrupted.
Molecular characterization of the aging potential of Chardonnay wines
by Pei HAN (Oenologie)
The defense will take place at 9h00 - Amphithéâtre ISVV 210 Chemin de Leysotte, 33140 Villenave-d'Ornon
in front of the jury composed of
- Alexandre PONS - Chargé de recherche - Université de Bordeaux - Directeur de these
- Vincent FARINES - Professeur - Université de Montpellier - Rapporteur
- Victor DE FREITAS - Full professor - UCIBIO/REQUIMTE, Departamento de Química e Bioquímica, Faculdade de Ciências da Universidade do Porto - Rapporteur
- Luigi MOIO - Full professor - Department of Agricultural Sciences, University of Naples Federico II, Portici, Italy - Examinateur
The finest Chardonnay wines produced in Burgundy are renowned for their aging potential. However, the molecular determinants that govern this capacity, namely resistance to oxidative phenomena, are not yet known. Given the importance of this distinctive trait, industry professionals also wish to have tools that allow them to assess the aging potential of their white wines at an early stage. This dissertation aims to address this knowledge gap by optimizing and comparing the performance of different analytical strategies for evaluating the aging capacity of Chardonnay white wines. This approach builds on current knowledge of the molecular markers involved in the oxidative evolution of white wine aromas, such as (R/S)-sotolon and Strecker aldehydes (methional and phenylacetaldehyde), as well as the ability to detect short-lived free radicals via spin trapping/EPR. By quantifying oxidation markers, we demonstrated the sensory contribution of methional and (S)-sotolon to the aroma of oxidized Chardonnay wines. We also clarified the impact of L(+)-lactic acid on the olfactory intensity of (R/S)-sotolon and Strecker aldehydes. Additionally, we optimized the operating conditions of the spin-trapping/EPR spectroscopic approach to monitor the formation and decay kinetics of the 1-hydroxyethyl radical (1-HER) during Fenton oxidation (H2O2, Fe2+) in white wines. Using a log-normal model, revealed how specific curve parameters, particularly index a, relate to the oxidation level of wines, especially their methional content. In other words, we established a link between a wine's radical reactivity and the presence of aroma compounds. Through a large number of wine analyses, we demonstrate that the spin-trapping/EPR test provides a more discriminating response that remains complementary to classical antioxidant assays, such as DPPH, ORAC, and FRAP. Finally, a complementary study on the effects of harvest date on aging capacity under controlled oxygenation conditions demonstrated the predictive value of early free radical detection by spin-trapping/EPR for subsequent cellar aging. This experimental protocol highlights the complementary roles of methional and sotolon to explain the oxidation of Chardonnay wines according to the level of maturity of the grapes.
Genetic diversity of root traits in Vitis spp. and potential for varietal innovation in drought-tolerant grapevine rootstocks
by Etienne PATIN (Ecophysiologie et Génomique Fonctionnelle de la Vigne)
The defense will take place at 9h00 - Colette & Josy Bové INRAE Grande Ferrade 71 Av. Edouard Bourlaux, 33140 Villenave-d'Ornon
in front of the jury composed of
- Xavier DRAYE - Professeur des universités - Université catholique de Louvain - Rapporteur
- Marion PRUDENT - Directrice de recherche - INRAE UMR Agroécologie - Rapporteur
- Laurent BOUFFIER - Chargé de recherche - INRAE UMR BIOGECO - Examinateur
- Massimiliano CORSO - Chargé de recherche - INRAE UMR Institut Jean-Pierre Bourgin - Examinateur
Climate change is forcing the wine industry to adapt to drought conditions. One of the levers for action is to diversify the range of suitable rootstocks, as the root system plays a key role in how plants respond to water shortages, through its development and its ability to acquire resources from the soil. However, identifying root traits that promote drought tolerance and can be integrated into a genetic improvement program remains an unresolved issue, particularly for perennial species such as vines. This lack of knowledge is due in particular to the time-consuming nature of root phenotyping and the limitations of high-throughput phenotyping. The latter is essential for estimating the genetic variability of root traits in a representative manner across large populations. Nevertheless, a better understanding of the genetic diversity of the root systems of drought-adapted wild Vitis species is essential to inform programs for the development of vine rootstocks adapted to future environments. The aim of this thesis is to quantify the inter- and intraspecific genetic variation of root traits in wild Vitis spp., establish their link with responses to drought, and identify proxies to facilitate their incorporation into rootstock selection schemes. To this end, a panel of 50 accessions, including 12 wild species, was studied in the form of cuttings or grafted with Floréal, through two experiments subjected to water deficit. These experiments made it possible to evaluate aerial responses during water deficit, as well as to characterize the root system at the morphological, functional, anatomical, and metabolomic levels. Multivariate and univariate approaches were used to study the link between genetic variation in root traits and responses to drought. The study of metabolism explored biomarkers for predicting root traits. In addition, the covariation between metabolism and root traits was studied, revealing a wider variation in metabolism in response to the environment, although this trend varies between species. Finally, a last experiment conducted in hydroponics and sand allowed us to study the genetic diversity of traits related to the dynamics of early root system establishment. This complementary experiment made it possible to evaluate the phenotypic plasticity of root morphology traits in response to the growing medium and to test their stability during plant development. All these results will make it possible to characterize root strategies related to drought responses in a panel of natural diversity and thus to evaluate their potential in vine rootstock selection programs.
ED Sciences Physiques et de l'Ingénieur
SYSTEM ENGINEERING APPROACH TO THE DEVELOPMENT OF URBAN DIGITAL TWIN.
by Zeeshan ALI (Laboratoire de l'Intégration du Matériau au Système)
The defense will take place at 14h00 - Amphithéâtre Jean-Paul DOM IMS - Laboratoire de l'Intégration du Matériau au Système (Bat. A31) , 351 Cours de la Libération, 33405 Talence Cedex
in front of the jury composed of
- Mamadou Kaba TRAORE - Professeur des universités - Université de Bordeaux - Directeur de these
- Sidharta GAUTAMA - Professeur - University of Ghent - Rapporteur
- Raymond HOUE NGOUNA - Maître de conférences - Ecole Nationale d'Ingénieur de Tarbes - Examinateur
- Nicolas DACLIN - Professeur des universités - IMT- Mines d'Alès - Rapporteur
- Pascale MARANGE - Maîtresse de conférences - Université de Lorraine - Examinateur
- Sébastien HENRY - Maître de conférences - IUT Lyon 1- Université de Lyon - Examinateur
This PhD thesis is a small part of a large-scale “university-wide” project called “Augmented Campus for World Class Transition" (ACT). This project aims to transform the University of Bordeaux (UB) into a living laboratory and incubator for experimental projects to achieve the socio-environmental transitions by engaging the community, multidisciplinary expertise, and external stakeholders. One of the core objectives of ACT is to “develop research provision for evidence-based decision-making". For this purpose, there is a need for a (digital) scientific tool in the urban ecosystem settings of the UB, and as a result this thesis started. The concept of digitalization is spreading across all sectors, including smart cities and urban ecosystems, leading to the emergence of "smart" society. The digital systems integrate data and (virtual) technologies, and these systems are increasing widely. In this context, Digital Twin (DT) has emerged as an innovative approach to manage the growing complexity of such systems by combining data-based and model-based engineering. The DT has already found applications in various domains including smart cities, playing a crucial role in cities digital transformation. As a result, the concept of Urban Digital Twins (UDTs) emerged in 2017-2018, that offers the integration of physical and virtual city environments. Despite progressive growth of UDTs since 2018, only few cities have developed their UDTs. This lack of UDT development is due to the (i) complexities inherit in the urban ecosystem and (ii) fragmented viewpoints of UDT from different research perspectives. The urban complexities, such as addressing the complex interconnected and interdependent phenomena of the urban ecosystem; addressing them at different scales; and incorporating the evolving and dynamic nature of urban ecosystem. The fragmented viewpoints such as, lack of UDT standards, fragmented UDT frameworks, integration of various technologies, applications and domain-oriented designs as well as the lack of systematic engineering approaches for the design and development of UDTs. This thesis responds to the following research questions: (1) How can holistic UDTs be built effectively that integrate multi-perspective urban phenomena at multiple scales? (2) What is the role and importance of spatial information technology and 3D city modeling in UDTs? (3) How can different stakeholders be integrated into UDTs? and (4) What is the system engineering approach that provides a holistic understanding for building a UDT? The overall objective of this thesis is to develop the UDT for UB that can address the urban phenomena of mobility and energy. The main contributions of this work are as follows: • A conceptual framework for the UDTs: A conceptual framework is proposed for the UDTs, which is based on software engineering architectural principles. This is a generic framework which provides a reusable and structured foundation that can one can reuse for the modeling and implementation of their UDT. It integrates multiple urban phenomena at multiple levels as well as incorporate stakeholders at different level that literature lacks. • A multi-formalism specification of the UB's UDT: This is achieved by modeling the UB UDT using UML, SysML, and HiLLS (High Level Language for System Specification) i.e. the graphical representation of DEVS (Discrete EVent System specification). The integration of multi-formalisms ensured the consistency across conceptual, architectural, and operational level implementation, by linking the descriptive UB UDT design with formal executable behavior. • Implementation of the UB UDT in a real-world environment: It is achieved by using the multi-modeling software environment (specifically AnyLogic), where we implemented the dimension of mobility and energy at university settings. Its implmentation and results demonstrate the practical applicability and validity of the proposed framework and multi-formalism specification.
Brownian Motion Near Complex Surfaces
by Nicolas FARES (Laboratoire Ondes et Matière d'Aquitaine)
The defense will take place at 13h30 - Amphithéâtre B 351 cours de la libération, Bâtiment A29 RDC, 33400, Talence.
in front of the jury composed of
- Thomas SALEZ - Directeur de recherche - Université de Bordeaux, CNRS - Directeur de these
- Marco POLIN - Professor - University of the Balearic Islands - Rapporteur
- Jasna BRUJIC - Professor - New York University - Rapporteur
- Lydéric BOCQUET - Directeur de recherche - Université Paris Sciences et Lettres, CNRS - Examinateur
- Vincent CROQUETTE - Directeur de recherche - Université Paris Sciences et Lettres, CNRS - Examinateur
Confined motions of soft particles are ubiquitous in microbiology. Examples include blood cells flowing in vessels, antibody recognition, or confined diffusion of synaptic neurotransmitters. These situations bring about viscous flows coupled to charged and soft confining entities, in presence of thermal fluctuations. Fluctuation-free scenarios have already proven the emergence of novel softness-induced near-contact forces, but the inclusion of fluctuations -- crucial at microscopic scales -- is yet to be explored. Aiming at unraveling the link between confined viscous flow, softness, and thermally-fluctuating -- i.e. Brownian -- motion, we combine holographic microscopy and statistical inference. This state-of-the art technique allows for a broadband characterization of the three-dimensional motion of a single, free, colloid diffusing in a viscous fluid near a charged rigid wall, with nanometric precision. Already in the case of a micrometric rigid bead, striking differences compared to bulk Brownian motion are measured and quantified. Namely, the statistics of displacements deviates from Gaussian distributions. Also, femtonewton-like bulk and surface forces, resolved at the fundamental thermal noise limit, are extracted from the trajectories. The novel case of a compliant colloid -- at the core of this thesis -- is even more puzzling. Specifically, we study the confined Brownian motion of single low-surface-tension viscous oil micro-droplets. While, at equilibrium, these soft droplets behave similarly as their rigid counterparts, at short time scales, we observe the emergence of novel transient piconewton-like inertia-less lift forces acting on the droplets, stemming from a thermally-induced visco-capillary coupling. These effects could tune transient migration strategies at microscopic scales, target finding or chemical reactions in crowded environments. Moving on to another topic, confined but active fluctuations are investigated via a more exotic fluctuating system, namely gliding algae C. Reinhardtii.
ED Sociétés, Politique, Santé Publique
Intersex bodies and social norms in Burkina Faso : between representations, experiences and healthcare systems
by Koukiyoani KOUTIANGBA (Les Afriques dans le Monde)
The defense will take place at 14h00 - Pas encore de réservation de Salle Université de Bordeaux, 3ter Pl. de la Victoire, 33000 Bordeaux
in front of the jury composed of
- Marc-Eric GRUENAIS - Professeure émérite - Université de Bordeaux - Directeur de these
- Janik BASTIEN-CHARLEBOIS - Professeure - Université du Québec - Rapporteur
- Laurence HERAULT - Professeure des universités - Aix-Marseille Université - Rapporteur
- Christophe BROQUA - Chargé de recherche - CNRS - Examinateur
- Alain GIAMI - Directeur de recherche émérite - INSERM - Examinateur
- Eric MACE - Professeur des universités - Université de Bordeaux - Examinateur
This anthropological research studies intersexuality in Burkina Faso through social representations, life trajectories and healthcare systems, analysing the influence of social and biomedical norms on the recognition of intersex people. The approach adopted is qualitative and ethnographic, conducted at several sites across the country. It is based on interviews with intersex people, their relatives, health professionals, traditional practitioners and institutional actors. Observations were also carried out in healthcare facilities and community spaces. This immersion provided an understanding of the diversity of trajectories, strategies employed and forms of agency developed in interactions between individuals, families and institutions. The results show that intersex people face many challenges from birth and throughout their lives. These difficulties are closely linked to social norms based on strict gender binary. To cope with this, they develop various strategies of discretion, adjustment or mobility in order to preserve their integrity and social belonging. When these strategies are no longer sufficient, they seek other alternatives, including medical care. Although this care exists, it remains limited by the absence of structured systems and by its often high cost and inaccessibility. On a theoretical level, the study is based on a Foucauldian and postcolonial reading of the relationship between knowledge and power. The analysis shows that biomedical care for intersexuality remains influenced by the colonial legacy and by the hierarchy between medical and cultural knowledge. This thesis contributes to the anthropology of the body and gender in Africa by shedding light on how intersex experiences reveal the links between social norms, medical knowledge and power dynamics in the social construction of the body and sex.
Real-life benefit of antithrombotic drugs for the treatment of lower limb peripheral artery disease (PAD)
by Loubna DARI (Bordeaux Population Health Research Center)
The defense will take place at 14h30 - Amphithéâtre 12 Campus Carreire 33076 Bordeaux Cedex
in front of the jury composed of
- Antoine PARIENTE - Professeur des universités - praticien hospitalier - Université de Bordeaux - Directeur de these
- Silvy LAPORTE - Professeure des universités - praticienne hospitalière - Univ. Jean Monnet, Mines Saint- Étienne, INSERM, U1059, SAINBIOSE, CHU Saint-Étienne, Service de Pharmacologie Clinique, F-42023 - Rapporteur
- Marie-Antoinette SEVESTRE-PIETRI - Professeure des universités - praticienne hospitalière - CHU Amiens-Picardie Site Sud – Entrée Principale - Rapporteur
- David-Alexandre TREGOUET - Directeur de recherche - Inserm U1219 Bordeaux Population Health directeur de l'équipe ELEANOR - Examinateur
- Alessandra BURA-RIVIERE - Professeure des universités - praticienne hospitalière - CHU de Toulouse - Hôpital Rangueil - Examinateur
- Joël CONSTANS - Professeur des universités - praticien hospitalier - CHU de Bordeaux- Hôpital saint-andré - CoDirecteur de these
Peripheral artery disease (PAD) represents a frequent and severe manifestation of atherosclerosis, associated with high morbidity and mortality due to major cardiovascular events and local complications leading to amputation. Despite its considerable public health impact, this condition remains less investigated than coronary or cerebrovascular diseases. Current antithrombotic strategies largely rely on outdated trials or extrapolations from other patient populations, although PAD exhibits specific pathophysiological and prognostic features that justify dedicated evaluation. This doctoral research aimed to generate new real-world evidence on the benefit and safety of antithrombotic strategies in PAD, by combining a methodological approach to validate identification algorithms with comparative observational studies. The first methodological component focused on validating algorithms for identifying PAD and chronic limb-threatening ischemia (CLTI) in French medico-administrative databases. Using hospital data from Bordeaux University Hospital (PMSI), the ICD-10 code I70.2 was shown to accurately identify hospitalized PAD patients, with excellent sensitivity and specificity. In contrast, algorithms developed for CLTI, based on the combination of atherosclerosis and tissue-loss codes, proved insufficiently specific, with low predictive values. These findings confirm the feasibility of robust observational studies on PAD using the French National Health Data System (SNDS), while underscoring the need for complementary clinical data to study the most advanced forms of the disease (CLTI). The second component involved several comparative pharmacoepidemiological studies. The first, conducted in the SNDS within an emulated target trial framework, compared aspirin and clopidogrel monotherapy after lower-limb revascularization and found no significant difference in the reduction of ischemic events or major bleeding, suggesting therapeutic equivalence between these agents. The second, conducted in the UK Clinical Practice Research Datalink (CPRD) among patients with both PAD and atrial fibrillation, showed an increased risk of major bleeding with rivaroxaban compared with apixaban, with no difference in ischemic outcomes. The third, which analyzed data from the COPART registry, found no clinical benefit of iloprost on amputation-free survival among patients with CLTI and even suggested a potentially deleterious effect of this treatment. Taken together, these studies illustrate the potential of real-world observational research to assess antithrombotic strategies in PAD under routine care conditions. They also highlight the inherent limitations of medico-administrative data, particularly the lack of detailed clinical information. In the future, linking administrative databases with clinical registries, hospital data warehouses, and biological or genomic information could overcome these limitations and enable more precise evaluations, ultimately guiding personalized therapeutic strategies for patients with PAD.
Contribution of metabolic disorders in liver disease among HIV-infected adults in low and middle-income countries.
by Marie PLAISY (Bordeaux Population Health Research Center)
The defense will take place at 14h00 - Salle 446 Salle 446, bât TP 4éme étage, Aile Sud, 146 rue Leo Saignat, 33000, Bordeaux, France
in front of the jury composed of
- Antoine JAQUET - Docteur - Université de Bordeaux - Directeur de these
- Hugo PERAZZO - Docteur - Evandro Chagas National Institute of Infectious Diseases -Oswaldo Cruz Foundation - CoDirecteur de these
- Linda WITTKOP - Professeure - Université de Bordeaux - Examinateur
- Anders BOYD - Chercheur - Université de Bern - Rapporteur
- Christian LAURENT - Directeur de recherche - Université de Montpellier - Rapporteur
- Victor DE LEDINGHEN - Professeure des universités - praticienne hospitalière - Echosens - Examinateur
- Moussa SEYDI - Professeur - CHU de Fann - Examinateur
- Patrizia CARRIERI - Ingénieure de recherche - Université d'Aix Marseille. - Examinateur
The global scale-up of antiretroviral treatment (ART) has significantly increased the life expectancy of people living with HIV (PLWH). Consequently, liver disease has become an increasingly important cause of morbidity and mortality in this population. Liver steatosis affects approximately 38% of PLWH and progresses more rapidly to fibrosis and cirrhosis than in the general population. Metabolic disorders, including obesity, dyslipidemia, and type 2 diabetes mellitus (T2DM), are well-established risk factors in high-income countries. However, their role in low- and middle-income countries (LMICs) is not well understood. Early detection in LMICs faces limitations due to restricted access to advanced diagnostic tools, such as biopsy and vibration-controlled transient elastography (VCTE) highlighting the need for simple, reliable alternatives. The main objective of this thesis was to assess the burden and predictors of liver disease, with a particular focus on liver steatosis, among PLWH in LMICs, and to evaluate the performance of serological scores for detecting liver steatosis in LMICs. This work is based on the Sentinel Research Network cohort of the IeDEA consortium, which enrolled PLWH aged ≥40 years on ART across twelve HIV clinics in Asia, Central/South America, and sub-Saharan Africa from 2020 to 2022. The prevalence of liver steatosis and fibrosis was 28.4% (95% CI, 26.5–30.7) and 7.6% (95% CI, 6.1–8.4), respectively, with regional variability. Metabolic disorders, including overweight/obesity, T2DM, and dyslipidemia were identified as key contributors to liver steatosis and fibrosis, whereas viral hepatitis showed no significant association. Over 3-years, 190 participants (20%) experienced steatosis progression (7 per 100 person-years), with pre-existing metabolic disorders identified as predictors of this progression. Exposure to integrase inhibitors-based regimens showed a trend toward this progression. Serological scores, including Hepatic Steatosis Index (HSI) and Fatty Liver Index (FLI), showed moderate discrimination for HSI (AUROC=0.74) and good discrimination for FLI (AUROC=0.80). Both scores exhibited good calibration, indicating consistency between estimated risks and measured outcomes, and good clinical utility in all regions, except in sub-Saharan Africa. Overall, this thesis provides comprehensive data on the burden and predictors of liver disease among PLWH in LMICs, highlighting the importance of integrating cardiometabolic screening and liver monitoring into routine HIV care to prevent progression and improve liver outcomes.
The quest for state power. The use of electoral marketing strategies during election periods in Senegal
by Segbene Francko Euloge AYOWA (Centre Emile Durkheim)
The defense will take place at 14h30 - Salle 5128 (code d'accès : 51280) Pavillon DKN 1030 Avenue des sciences sociales G1V 0A6, Québec (Canada)
in front of the jury composed of
- Yves DELOYE - Professeur des universités - Université de Bordeaux - Directeur de these
- Éric MONTIGNY - Professeur des universités - Université Laval - Directeur de these
- Arnaud MERCIER - Professeur des universités - Université Paris 2 Panthéon-Assas - Rapporteur
- Anne-Marie GINGRAS - Professeure des universités - Université du Québec à Montréal - Rapporteur
- Marc André BODET - Professeur agrégé - Université Laval - Examinateur
- Cédric JOURDE - Professeur agrégé - Université d'Ottawa - Examinateur
Based on a collection of primary sources, interviews, and non-participant observation, this thesis addresses both the adoption and integration of political marketing by political parties during election periods and the level of knowledge of political actors regarding political marketing. To this end, we studied the cases of three Sub-Saharan political groups operating in the same Senegalese jurisdiction, namely the Benno Bokk Yakaar coalition, the Idy President coalition, and the Sonko/Diomaye President coalition, in the context of the campaigns for the last two presidential elections (2019 and 2024). Drawing on two theoretical frameworks of political marketing, Jennifer Lees-Marshment's political party orientation model (C.P.M) and Neil Collins and Patrick Butler's competitive positioning model, as well as our six proposed hypotheses, our analysis reveals clear conclusions. Applied empirically to our Senegalese cases, we find that Collins and Butler's competitive positions model is verified in light of the strong competition existing in the political market during the election campaigns studied and the different election results of our political coalitions, while Lees-Marshment's political party orientations model amply confirms the predominance of product-oriented parties (POP), relatively sales-oriented parties (SOP), and an absence of product-market parties (MOP). This weak integration of political marketing techniques and concepts by our political parties can be explained by the Senegalese context, which is not conducive to the practice of political marketing. This context is disadvantaged by the lack and absence of several conditions favorable to the adoption and practice of political marketing in a democracy and within political parties. Furthermore, our research indicates that political leaders within the political parties studied have a low level of knowledge about political marketing. This conclusion also contributes to the slow adoption and integration of electoral marketing strategies within these political parties during election periods and confirms, to a certain extent, that political marketing is not yet accepted within Senegalese political culture. Our results also confirm that there is an obsession with the use of digital platforms by our political parties to convey their political messages and, furthermore, the relevance of using the political marketing mix concept (the 4P) in the Senegalese context. Pending the improvement of certain conditions conducive to the deployment of political marketing in a democratic context, the latter is more flexible and adapted to Senegalese parties during election periods. Keywords: Political marketing, political communication, elections, Senegal and West Africa, democracy, digital platforms, political coalitions, political marketing mix.