NCube/papyrus huggingface dataset:
Réorganisation cérébrale chez l’adulte sourd : de la privation à la restauration auditive

It is estimated that 5% of the world’s population suffers from a disabling hearing loss, including 34 million children. This sensory deficit, when it occurs at birth or in the first years of life, has multiple repercussions on the brain and neurocognitive development. The brain reorganization taking place in the brain of early-deaf individuals is an area of research highly valued by the scientific community but for which many questions remain unanswered. Thus, the main objective of the articles in this thesis is to improve our knowledge of brain reorganization mechanisms, both at the functional and structural levels, in deaf individuals. This will allow a better understanding of their impact on the behavioural adaptations of deaf individuals.  To do this, we investigated, through functional magnetic resonance imaging, the relationship between brain activation and behavioural performance in a task involving biological motions in early-deaf adults, compared to hearing peers. Article 1 reveals that deaf individuals are more sensitive to the recognition of biological motion, including emblems, than hearing individuals. In addition, this behavioural specificity, observed only in deaf individuals, is accompanied by extensive recruitment of the regions included in the superior temporal gyrus, such as the primary auditory cortex but more particularly, the planum temporale. Our results support the presence of intermodal reorganization, which is expressed by brain recruitment of auditory regions during complex visual stimuli, leading to improved recognition of the biological motion in early deaf adults.  On the other hand, we wanted to specify the mechanisms of structural brain reorganization. Due to the heterogeneity of the results previously reported in the literature on changes in grey matter and white matter in early-deaf children, adolescents, and adults, the completion of a systematic review identified all the structural changes obtained through various magnetic resonance imaging analysis techniques. The second article of this thesis offers a generalization of structural alterations. It also integrates a clinical frame to the understanding of these anatomical changes to optimize the language and neurocognitive development of these individuals.   Together, these results contribute to a better appreciation of brain changes following an early hearing loss at both the functional and structural levels. Besides, they offer a developmental perspective to these changes by describing adaptive behaviours and the neurocognitive profile of these individuals, with providing new insights into hearing and language restoration strategies.

Keyphrases: Neuroimagerie, Deafness, Neuroplasticity, Neuroimaging, Brain development, Language
Political conflict as moral conflict : multiculturalism and the nation in Germany (2015-2017)

This dissertation examines, from a Durkheimian perspective, political conflict in Germany around the issues of multiculturalism, immigration, and national identity within the context of the Refugee Crisis beginning in 2015 and ending roughly with the German Federal Election in September 2017. It identifies four moral ideals, or ideal visions of the German community, that motivated political actors during this period: the Autonomen ideal that rejects all forms of power and domination; the ideal of Verfassungspatriotismus (Constitutional Patriotism) of the SPD (and parts of the CDU); the ideal of the cultural or ethnocultural nation of much of the AfD (and the CSU and WerteUnion); and the ideal of the biological nation on the far-right. At the heart of each moral ideal is a sacred object that serves as a moral authority that legitimates certain moral prescriptions, and leads to a set of moral truths and moral judgments, the totality of which Émile Durkheim identifies as a moral fact. For the Autonomen and adherents of Verfassungspatriotismus the sacred object is the individual understood through the concept of human dignity. For others the sacred object is the German nation, understood either in an (ethno)cultural sense or a biological sense. As the dissertation argues, these different moral ideals are inherently profanatory to each other, such that the moral prescriptions inspired by one sacred object (human dignity) directly violate the sacred object of the other (the nation), and vice-versa. These ideals all compete with each other for power and influence within the German political sphere as a means to gain access to (or to dismantle) state power. The result is political conflict that takes place essentially within a moral framework. These conflicts occur in the legal domain, in battles over party leadership and membership, and through political violence; they touch on a number of key issues such as free speech, multiculturalism, and political extremism. This dissertation seeks to understand these conflicts through the prism of Durkheim’s concept of the moral fact and to develop a Durkheimian sociology of moral conflict. In this analysis, the dissertation draws on Randall Collins’ conflict theory, which Durkheim’s work also largely inspires.

Keyphrases: Émile Durkheim, Verfassungspatriotismus, moral truth, moral fact, legitimation of authority, right-wing populism, extremism, free speech, hate speech
Géographie du système alimentaire des Inuit du Nunavik : du territoire nourricier au supermarché

This thesis focuses on the transition of Nunavik’s food system and on the consequences of that transition for the region’s inhabitants. The thesis’s hypothesis is that the food system’s new territorial configuration changes the interactions between humans and the natural environment, and thus becomes incompatible with Nunavik’s ecosystems as well as Inuit culture and identity. Intensifying relations between the Inuit economy and the globalized economy put northern territories in a position of unequal exchange and dependency in relation to producers and suppliers from an exogenous agri-food sector that offers northern residents few opportunities to be heard. Food market sovereignty is thus severely restricted, which harms Inuit health and well-being. This thesis explores potential solutions for improving the food system’s resilience, such as developing community gardening projects and improving access to traditional foods. The data on which the four articles of this thesis are based was collected between October 2015 and March 2019 in the northern villages of Kuujjuaq and Kangiqsujuaq, in Nunavik. The variety of methods used, combining semi-constructed interviews, the development of mental maps, soil analyses and participatory workshops, made it possible to meet the triple challenge of interdisciplinarity, participatory action research, and terrain particularly difficult to access. The results illustrate that traditional foods from hunting, fishing and gathering activities remain major factors for the Inuit in their interactions with the natural environment and in their well-being, although those activities now represent only a small fraction of the food supply. Loss of mobility and the adoption of a new lifestyle, accompanied and made possible by the food system’s transition, have disturbed the interactions between humans and the natural environment on various levels. The greatest pressure exerted on the natural environment originates from human activities carried out elsewhere in the world and from an incompatible consumption model that generate numerous negative externalities on the environment and human health. One of the most significant contributions of this thesis is to have demonstrated the mechanisms by which nutritional, social, climate and energy issues are interrelated. The conclusion, pointing to the cumulative consequences of climate change, environmental contamination and colonization, summarizes the issues confronting Nunavik’s socio-ecological system.

Keyphrases: Nunavik, food system, food sovereignty, resilience, arctic, urban agriculture
Autonomie des femmes atteintes du syndrome des ovaires polykystiques : entre gestion de la maladie et approche restaurative de la santé

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women of childbearing age. It has a significant impact on quality of life and is one of the major causes of infertility. It is also associated with serious chronic conditions such as type 2 diabetes, hormonedependent cancers, and cardiovascular disease. While it is prevalent and has serious consequences, women's experience of care reflects problematic dimensions: lack of awareness and information, delays in diagnosis, insensitivity, inattention, and trivialization. Research shows that women are dissatisfied with commonly prescribed treatments such as the contraceptive pill. They report lacking treatment options and would be interested in other modalities of care. Research on PCOS also emphasizes the importance of lifestyle (e.g. nutrition and stress management) that can improve the metabolic and endocrine profile and have a positive impact on reproductive function. The general lack of attention to this condition is thus an interesting case study, reflecting systemic injustices in medicine. The objective of this thesis is to examine issues related to the autonomy of women affected by PCOS in the context of health care and fertility, and to propose ways to promote the expression of autonomy. The thesis analyzes these issues in the context of chronic disease, whereby treatment focuses on alleviating infertility and neglects restorative approaches to health, particularly through effective lifestyle changes. The analysis is based on the conceptual framework of relational autonomy, and considers two possible modes of autonomy expression: episodic and programmatic. Awareness of these issues makes it possible to reflect on what a holistic approach could bring to PCOS care, considering both disease management and a restorative approach to health. To consider the ethical challenges related to the care of PCOS, this thesis employs both a conceptual-normative and an empirical perspective. Both allow a better understanding of the shortcomings of the current medical approach and an informed recommendation for better ways of responding to these challenges. By recognizing the need for prevention and management of PCOS, as well as a restorative approach to health, this thesis has substantial implications for healthcare professionals and women, suggesting ways of supporting both episodic and programmatic autonomy and empowerment of affected women.

Keyphrases: Empowerment, Recherche narrative, Polycystic ovary syndrome (PCOS), Autonomy, Empowerment, Feminist perspective, Narrative research, Disease management, Restorative approach to health
Les primates non humains ont-ils une théorie de l’esprit ? =

Theory of mind, the ability to attribute mental states to oneself and to others, is a multifaceted phenomenon as there are different kinds of mental states (intention, knowledge, belief, etc.). Is theory of mind present in other animals, particularly in nonhuman primates, or is it unique to humans? This question has been investigated for almost 40 years and, despite some methodological difficulties and controversies (e.g. mindreading vs. behavior-reading), important advances have been made since the early 2000s. In fact, we now know that great apes behave according to others’ goals, intentions, visual perspective, and knowledge, and, to a lesser extent it seems, to others’ auditory perspective. Furthermore, recent studies suggest that these hominids also understand false beliefs, albeit implicitly, a capacity that was previously thought to be found only in humans. Understanding false-belief is central to theory of mind as it requires one’s to realize that mental states are internal representations rather than direct reflections of reality, and can therefore be inaccurate. Future investigations should explain the discrepancies between these recent studies and previous ones which reported negative results, and should also clarify the nature of the difficulties experienced by great apes when it comes to reality-incongruent mental states. Although noteworthy efforts have been made, research is still mostly centered around great apes, especially chimpanzees, so much so that we still know very little about theory of mind abilities in other primates. Visual and auditory perspective-taking have nevertheless been reported in some Old World monkeys, as well as their understanding that knowledge is acquired through these sensory modalities. Some work has also shown ability to attribute goals and intentions to others in New World monkeys. Thus, what seemed to be a difference of kind between humans and other primates now appears to be mainly one of degree.

Keyphrases: Primates, Social cognition, Theory of mind, False-belief, Chimpanzee
Nouvelles approches dans l’immunothérapie de la leucémie aigüe lymphoblastique utilisant les récepteurs chimériques d’antigène

Immunotherapy has allowed major advances in cancer therapy. The treatment using modified T cells with a chimeric antigen receptor (CAR) completely changed the vision of leukemia therapy. The efficiency against resistant cancer paved the way to cellular and gene therapy in this context. Despite very positive results at first, the disappearance and exhaustion of therapeutic cells seems to be a major problem to maintain the efficiency of the CAR treatment and prevent relapses. The work of this thesis is to allow the use cell types other than T cells for CAR therapy. The hypothesis is that NK cells or hematopoietic stem cells (HSC) could overcome the limitation of CAR therapy using T cells. To allow the use of CAR NK cells, a major technical issue is the transduction by viral vectors. The work presented here shows the use of BaEV envelope to pseudotype vectors allows an efficient transduction of NK cells. Using this method, we were able to produce large amounts of CAR NK cells, showing the possibility to use NK cells in CAR therapy. The use of HSC in CAR therapy, could allow the permanent replenishment of the pool of CAR T cells once exhausted. Despite that advantage, the overexpression of a CAR receptor on all hematopoietic cells coming from those HSC could be an issue. To allow the use of HSC, we developed short specific promoters restraining the expression of the transgene to a precise population. We prove the specificity of a T cell promoter and demonstrated the possibility to use it in CAR therapy using HSC. This work is a proof of concept of the use of other population than T cells in CAR therapy.

Keyphrases: Transduction, Cancer, Cellule T, Immunotherapy, Leukemia, NK cell, Hematopoiteic Stem Cell, Transduction, Specific Promoter, T Cell
Rôle de l’ubiquitine ligase March1 dans le cancer et le diabète de type II

March1 plays a critical role in the immune response regulation. This ubiquitin ligase downregulates the expression of antigen presentation and costimulatory proteins, such as MHC class II and CD86, as well as other proteins involved in the cellular metabolism, such as the amino acid transporter CD98 and the insulin receptor. The ubiquitination of these proteins by March1 alters the antigen presentation and proliferative capacities of dendritic cells and CD8+ T cells, respectively. However, the effect of MHC class II ubiquitination by March1 on the development and the migration of dendritic cells are not known, and the physiological implications of March1 in other cells, such as CD8+ T cells, are not completely understood. In this thesis, we show that MHC class II ubiquitination by March1 is specifically required for the migration of monocyte-derived dendritic cells (moDCs) from skin to skin draining lymph nodes (sdLN). This effect is cell intrinsic and correlates with the expression level of proteins involved in immune cell migration, IRF4 and CCR7. In a melanoma mouse model, the deficiency of MHC class II ubiquitination is associated with exacerbated tumor growth and impaired moDCs migration from tumor to tumors-draining LNs. Using GM-CSF producing tumors, we found that this cytokine increases the expression of IRF4 and CCR7 in moDCs and improves their migration. On the other hand, we show that March1 deficiency exacerbates obesity-induced insulin resistance. Adipose tissue from these mice was enriched in CD8+ T cells with an effector/memory phenotype. Adoptive transfer of splenic CD8+ T cells showed that March1 intrinsically affects the phenotype of these cells in obese adipose tissue and exacerbates insulin resistance. Consistent with the role of March1 in the ubiquitination of CD98 and insulin receptor, the metabolic activity of CD8+ T cells was increased in absence of March1. Overall, we showed that March1 regulates the migratory capacity of moDCs and the metabolic activity of CD8+ T cells. The involvement of these effects in the development of melanoma cancer and type II diabetes suggests that March1 can be a target for therapeutic strategies against these pathologies.

Keyphrases: March1, MHC class II, Dendritic cells, cancer, Diabetes
Interactions corticales impliquées dans la production des mouvements de la main chez le singe capucin

In primates, the refinement of hand movements is associated with the appearance of additional cortical premotor areas. Each of these premotor areas appears to have a specialized function in the motor control of the hand, supporting the idea that they have appeared during evolution to support an increased behavioral repertoire. In order to participate in the execution of this vast repertoire, it is suggested that the premotor areas modulate the motor outputs of the primary motor cortex (M1), a cortical area that plays a key role in the production of voluntary movements. Indeed, thanks to their numerous cortico-cortical projections to M1 as well as their projections to sub-cortical structures also innervated by M1, premotor areas are in an ideal position to modulate the motor outputs of M1. Nevertheless, the contribution of these anatomical projections to the production of hand movements is still unclear. The function of these projections, however, is important to investigate in order to better understand the cortical interactions that underlie the increased motor repertoire of primates. As an integral part of this research context, the experiments presented in this thesis aim to characterize the cortical interactions between the premotor areas and M1 involved in hand movements in the capuchin monkey. In a first study, the modulatory effects of ventral premotor cortex (PMv) on M1 outputs were investigated (Chapter I). In a second study, the modulatory effects of the dorsal premotor cortex (PMd) were studied and compared to those of PMv (Chapter II). Lastly, in a third study, the modulatory effects of the supplementary motor area (SMA) were examined and compared to those of PMv and PMd (Chapter III). In summary, the results presented in this thesis offer a new perspective on the cortical interactions linking the premotor areas to M1. It is shown that each premotor area influences the outputs of M1 in a unique way. This supports the idea that each premotor area plays a specialized role in the motor control of the hand and is able to accomplish this function, in part, through its modulation of M1 outputs. These results contribute to a better understanding of the cortical interactions that underlie the refinement of hand movements accompanying the evolution of the motor system.

Keyphrases: interactions, hand, movement, primary motor cortex, premotor areas
Les facteurs de risque maternels, la santé pondérale et cardiométabolique des jeunes, et l’importance des habitudes de vie

Maternal and children’s health are major worldwide public health concerns. The current thesis aimed to explore the impact of maternal health during pregnancy on children’s and adolescents’ health and included three original research projects. The first study found that a prenatal exposure to independent or combined suboptimal gestational factors (SGF : gestational diabetes mellitus, hypertensive disorders during pregnancy, maternal smoking during pregnancy) was positively associated with obesity and cardiometabolic risk factors in children around puberty, and these associations were sex-dependent. The second study found that children exposed to one SGF display a similar physiological response in terms of mechanical efficiency and substrate oxidation at rest and during exercise (submaximal and maximal) in comparison with non-exposed children. The third study of the thesis found that light-intensity physical activity reduced the adverse impact of prenatal exposure to combined SGF on high density lipoprotein-cholestrol levels in boys. A sleep duration within the range of the current Canadian recommendations for sleep did not mitigate the risk of high waist circumference (children) and obesity (girls) in a context of exposure to maternal smoking during pregnancy. Furthermore, other lifestyle factors such as moderate-to-vigorous physical activity and a healthy diet (intakes of: fruits and vegetables, grains, and dairy products), did not mitigate the adverse impact of a prenatal exposure to independent or combined SGF on children’s risk of obesity and cardiomeatbolic outcomes. Taken together, these results suggest that it is important to continue maternal SGF prevention and management programs to provide optimal health for children. Moreover, future studies should also develop and evaluate the impact of lifestyle habits interventions to design future prevention strategies during childhood and adolescence to reduce obesity and cardiometabolic risk factors in this population.

Keyphrases: Pregnancy, Fetal programming, Pediatric obesity, Cardiometabolic risk factors, Sleep, Physical activity, Diet, Exercise physiology
Régulation par l’activité glycinergique des mécanismes cellulaires et moléculaires durant la neurogenèse embryonnaire

In the adult central nervous system, glycine is mainly known as an inhibitory neurotransmitter in mature neurons, thereby regulating the neural network activity. Paradoxically, during embryogenesis, the same neurotransmitter generates excitatory transmission and induces the first electrical signal in immature neurons. The role and functional significance of this change in glycinergic activity during neurogenesis are still unknown. In this study, we used zebrafish embryos as a model to explore the glycine-dependent molecular and cellular mechanisms in neural stem cells (NSCs).  First, we developed an in vivo analysis method based on two main elements: a transgenic line that expresses GFP within NSCs and the RNA sequencing technique. This method of analysis was used to determine glycine-dependent molecular mechanisms in NSCs. We identified several candidate genes whose expression is modulated by the glycinergic activity. These genes participate in five different canonical signaling pathways including the calcium signaling pathway, TGF-beta, Shh, Wnt and p53. To further understand these molecular mechanisms, we focused our investigation on the regulation of p53 signaling by the glycinergic activity. Indeed, we have demonstrated that glycinergic activity promotes the survival of NSCs by regulating p53 signaling and more specifically acting on NSC-nestin + subpopulation during neurogenesis. Finally, we explored the regulation of lnx1 expression by glycinergic activity. We have demonstrated that glycine/lnx1 signaling regulates the proliferation of NSCs via the modulation of Notch activity during neurogenesis. In conclusion, during this thesis project, I highlighted several molecular and cellular mechanisms modulated by the glycinergic activity in NSCs. These relevant results may contribute in the future to the understanding of the physiopathology related to glycinergic activity dysfunctions and the identification of new therapeutic targets.

Keyphrases: Glycine, Cellules souches neurales, p53, lnx1, Zebrafish, Neurogenesis, NSCs, Notch signaling