ED Entreprise Economie Société
A Socio-Territorial Analysis of Inequality in Chile, Colombia, and Mexico
by Thibaut PLASSOT SANSANS (BSE - Bordeaux sciences économiques)
The defense will take place at 15h00 - Salle de thèse 16 avenue Léon Duguit Bât. H2 CS 50057 33608 Pessac
in front of the jury composed of
- Matthieu CLEMENT - Professeur des universités - Université de Bordeaux - Directeur de these
- Eric ROUGIER - Professeur des universités - Université de Bordeaux - CoDirecteur de these
- François COMBARNOUS - Professeur des universités - Université de Bordeaux - Examinateur
- Eduardo ORTIZ-JUAREZ - Assistant professor - King's College London - Examinateur
- François ROUBAUD - Directeur de recherche - IRD / Université Paris-Dauphine - Rapporteur
- Vera CHIODI - Maîtresse de conférences - Université Sorbonne / IHEAL - Examinateur
- Oscar MARTíNEZ-MARTíNEZ - Full professor - University Iberoamericana-Mexico - Rapporteur
This dissertation examines, across four chapters, how social position and territory jointly shape inequality, social mobility, and inequality of opportunity in Chile, Colombia, and Mexico. Chapter 1 places social classes along an urbanization gradient and shows that territory differentiates mainly the two ends of the income distribution. Chapter 2 finds that in intermediate territories parents' educational aspirations for their children are nearly universal, whereas their expectations depend on their social position and their territory. The gap between aspirations and expectations therefore varies widely depending on circumstances. Chapter 3 measures social mobility and inequality of opportunity within a single framework and reveals the considerable weight of territorial circumstances in the latter. Chapter 4 shows that in Mexico access to the middle class is most likely for those raised around cities of 350,000 to one million inhabitants. Finally, the conclusion interacts social origin and territory and shows that territory weighs most on individuals from disadvantaged backgrounds and, conversely, that the influence of family circumstances diminishes in the most urbanized territories.
ED Sciences de la Vie et de la Santé
Osteocyte role in bone repair, using in vivo and in vitro models
by Léa GELLEE (Bioingénierie tissulaire)
The defense will take place at 14h00 - Amphithéâtre BBS 2 rue du Dr Hoffman Martinot 33000 Bordeaux Bâtiment Bordeaux Biologie Santé (BBS)
in front of the jury composed of
- Aline BOZEC - Professeure des universités - University Erlangen-Nürnberg / Department of Rheumatology and Immunology - Rapporteur
- Stéphane PALLU - Professeur des universités - Université d'Orléans / Laboratoire Biologie, Bioingénierie et Bioimagerie Ostéo-Articulaires - Rapporteur
- Maude GERBAIX - Maîtresse assistante - Université de Genève / Département de médecine - Examinateur
- Frédéric VELARD - Ingénieur de recherche - Université de Reims Champagne-Ardenne / EA 4691 Biomatériaux et inflammation en site osseux - Examinateur
The regeneration of large bone defects remains a major clinical challenge. When the volume of tissue to be regenerated exceeds the bone's intrinsic repair capacity, filling or reconstructive strategies are required, notably bone grafting. Osteocytes, now recognized as major regulators of bone homeostasis, may also participate in bone repair. Studies, particularly in fatigue fracture models, have revealed changes in osteocyte network organization and in the expression of molecules produced by these cells in the vicinity of lesions. However, their contribution to the repair of large bone defects remains poorly characterized. The localization of osteocytes within the mineralized matrix directly exposes them to changes in their microenvironment during bone repair. This thesis aimed to determine how osteocytes adapt to these changes and which factors modulate these responses. To characterize these adaptations, a murine critical-size calvaria defect model was used. The lesion induces a reorganization of the osteocyte network, associated with changes in dendrite morphology and number, osteocyte survival, and the expression of proteins such as Sema3A and podoplanin. These adaptations vary according to the distance from the defect and evolve during repair, highlighting the spatial and temporal organization of the osteocyte response. We then investigated three factors potentially modulating these adaptations: aging, the presence of a bone graft, and oxygen availability. Aging is a major concern in the context of the global aging of populations, as it is associated with changes in bone tissue that may progressively impair its ability to respond to injury. In our model, aging did not alter all osteocyte responses induced by the lesion, but some morphological and molecular adaptations of the network were altered with age. The presence of a bone graft can locally modify the cellular and matrix environment of the host bone and influence osteocyte responses. Cellular and acellular grafts were therefore compared to assess the influence of viable cells within the graft. Few differences were observed between the conditions regarding bone repair, mineralization, or the response of host bone osteocytes. Finally, low oxygen availability represents an important component of the osteocyte microenvironment, particularly given their localization within the mineralized matrix and changes in vascularization during repair. An in vitro approach combining morphological, metabolic, and transcriptomic analyses showed that different oxygen levels modulate osteocyte transcriptional and metabolic profiles. However, soluble factors produced by osteocytes did not induce major changes in gene expression in endothelial cells. Overall, these findings show that the osteocyte network adapts to changes in its microenvironment during bone repair through spatially and temporally organized responses. These adaptations depend on the biological context, highlighting the importance of considering osteocytes within their tissue environment. These findings therefore support moving beyond a static and homogeneous view of osteocyte biology and considering osteocytes as cells whose functions are shaped by a dynamic and complex environment. New approaches enabling this complexity to be explored will contribute to a better understanding of the role of osteocytes in bone repair.
Tissue and Molecular Biomarkers Predictive of Response to Neoadjuvant Treatment in Rectal Cancer
by Benjamin FERNANDEZ (BoRdeaux Institute of onCology)
The defense will take place at 14h30 - Salle Vasco De Gamma Hôpital de Haut Léveque Bâtiment Magellan 1 1 Avenue Magellan 33600 Pessac
in front of the jury composed of
- Samuel AMINTAS - Maître de conférences - praticien hospitalier - Université de Bordeaux / CHU de Bordeaux - Directeur de these
- Anais PUJALS - Professeure des universités - praticienne hospitalière - Université Paris-Est Créteil / APHP - Rapporteur
- Gilles MANCEAU - Professeur des universités - praticien hospitalier - Sorbonne Uiversité / APHP - Rapporteur
- Etienne BUSCAIL - Professeur des universités - praticien hospitalier - Université Paul Sabatier (Toulouse III) / CHU de Toulouse - Examinateur
- Caroline GRONNIER - Professeure des universités - praticienne hospitalière - Université de Bordeaux / CHU de Bordeaux - Examinateur
Management of rectal cancer has become increasingly individualised, with diversified neoadjuvant strategies and growing use of organ preservation. In our centre over 25 years, postoperative morbidity fell markedly while long-term survival remained stable. This makes it essential to choose the right treatment for each patient, which requires predicting tumour response before treatment. Current radiological, endoscopic and biological tools remain insufficient when used alone. This thesis seeks tissue biomarkers that predict response to neoadjuvant treatment, through a translational approach running from proteomics to clinical evaluation. Proteomic analysis of pretreatment biopsies led us to study the CDH17/Wnt/β-catenin pathway. Functional experiments confirmed that CDH17 regulates this pathway, with model-dependent effects and an exploratory radiosensitisation signal. In a cohort of 105 patients, nuclear β-catenin expression on the biopsy complements tumour size. Together they reach an AUC of 0.823 before any treatment, comparable to a model including restaging MRI, and a simple two-criterion score separates patients from 82.5% to 5.6% good responders. A second proteomic approach identified cytokeratin 19 (KRT19) as a marker of an epithelial state associated with response. These exploratory results call for external validation. A prospective cohort followed by a randomised trial are planned, to guide treatment choice before surgery and the decision between organ preservation and surgery after treatment.
Modelling the pathological oscillations generation mechanisms and network dynamics of the basal ganglia
by Elena NICOLLIN (Institut des Maladies Neurodégénératives)
The defense will take place at 10h00 - Amphithéâtre Broca Centre Broca Nouvelle-Aquitaine 146 rue Léo Saignat 33076 Bordeaux Cedex
in front of the jury composed of
- Catalina VICH - Professeur - Universitat de les Illes Baleares - Rapporteur
- Arvind KUMAR - Associate Professor - KTH Royal Institute of Technology - Rapporteur
- Benoît GIRARD - Directeur de recherche - CNRS / Sorbonne Université - Examinateur
- Jyotika BAHUGUNA - Chaire de professeur junior - Université de Strasbourg - Examinateur
Parkinson's disease (PD) is characterized by excessive oscillatory synchronization in the beta band (13-30 Hz) throughout the cortico-basal ganglia-thalamic (CBGT) network. Although these oscillations are a hallmark of the disease and correlate with motor symptoms, the circuit mechanisms that generate them remain unclear. Their properties, such as frequency, power and distribution across nuclei, also vary substantially across species and recording methods, raising the question of whether they reflect a single pathophysiological process or several distinct rhythms produced by different circuit mechanisms. This thesis investigates these generation mechanisms and how they differ across species. The first part is a review of beta oscillations in PD patients, MPTP-treated monkeys and 6-OHDA-lesioned rodents. It first addresses methodological considerations and argues for focusing on spiking activity as a more direct indicator of local circuit dynamics than local field potentials. A reanalysis of published datasets with a standardized pipeline then reveals pronounced interspecies differences in the frequency, power and anatomical distribution of beta oscillations, and in their response to circuit manipulations. Low-beta synchronization (≤15 Hz) characterizes patients and parkinsonian primates, while dopamine depletion in rodents mainly enhances synchronization at higher frequencies, which is also found in patients but is not exclusive to the pathological state. These findings argue against a single mechanism, and suggest that the frequency, power and phase relationships of beta oscillations across CBGT populations form signatures of their generating circuits. The second part tests this hypothesis with a CBGT network model constrained by either rodent- or primate-specific synaptic, neuronal and network parameters. The negative-feedback loops of the network were studied as candidate generators: they are the subthalamopallidal loop, the striatopallidal loops linking prototypic GPe neurons to striatal D2 projection neurons through fast-spiking interneurons or arkypallidal neurons, and the loop formed by the hyperdirect pathway and the thalamic feedback to the cortex. With experimentally derived time constants, the subthalamopallidal loop oscillates above the beta range in both species, while the striatopallidal and hyperdirect loops generate low-beta oscillations. Importantly, each loop produces a distinct pattern of phase relationships between populations, which can be used to identify the underlying generator. In the full network, generators behave as coupled oscillators: their interactions can suppress oscillations, shift their frequency continuously between low and high beta, or produce abrupt jumps in frequency. Phase relationships reported experimentally from rodents match a striatopallidal generator. In the primate model, low-beta oscillations persist only when cortical feedback is present, which points to the hyperdirect loop and provides phase predictions testable in future recordings. These results suggest that pathological beta oscillations arise from distinct mechanisms in rodents and primates. Finally, the third part addresses the connection strengths of the network, which are poorly constrained by experimental data. We applied simulation-based inference to the rodent model to estimate the connection gains compatible with neuronal responses to optogenetic stimulation in mice. The data consist of the activities of D2, STN, prototypic and arkypallidal neurons, recorded during stimulation of D2 neurons, STN neurons, or both. The inferred posterior distributions identify which connections are well constrained by these responses and which can compensate for one another. Overall, this work supports the coexistence of multiple circuit-specific beta rhythms and highlights the importance of species-specific constraints when relating models of their generation to experimental data.