NCube/papyrus huggingface dataset:
Lectures matérialistes de Leibniz au 18e siècle

In this dissertation, I study the unexpected reception of Leibniz's philosophy in the 18th century French materialism. The aim is to identify the leibnizian concepts, arguments or images that are used by La Mettrie, Diderot, d'Holbach and Helvétius to build their own thoughts. Three kinds of results are shown. Firstly, to understand better the origins of French modern materialisme and particularly its relationship to 17th century metaphysics. In this perspective, this stydy shows that materialists do not necessarilyu reject metaphysics but rather use it for their own goals. Secondly, to show the role of Leibniz in the in the elaboration of a so-called radical philosophy, which means to question the common idea that radicalism originates from spinozism. Lastly, by looking at the materialists uses of Leibniz's concepts, it tries to identify new possible interpretations of his philosophy, more precisely to consider the historical reception of leibnizian philosophy as a way to reveal his theoretical potential.  This work is divided in two parts : in the first one, it studies the mediations by which Leibniz's philosophy was introduced in France in the 18th century (Wolff, Du Châtelet, Maupertuis). In the second one, it examines four different uses of the leibnizian philosophy, namely, in La Mettrie, Diderot, d'Holbach and Helvétius.

Keyphrases: Leibniz, Diderot, Helvétius, La Mettrie, Maupertuis, Wolff, Du Châtelet, D'Holbach, 18th century, Materialism
Comment favoriser la communication thérapeutique avec une population vulnérable ? Des approches et des outils pour les professionnels prenant en charge les mineurs non accompagnés

In France, unaccompanied minors (UMs) encounter several obstacles that can have negative effects on their mental health. Health and social workers must develop and implement approaches and tools that are adapted to the realities of UMs, and that encourage a space to foster discussions. Based on a review of the literature, this article explores the mental health status and needs of UMs and highlights the approaches and tools developed and implemented by professionals to encourage communication with UMs (e.g., intercultural approach, interdisciplinary work, art therapy). Based on results from the review, we suggest recommendations for professionals and public authorities.

Keyphrases: Communication, France, Unaccompanied minors, Mental health, Social and health workers, Communication, Intercultural approach, Interdisciplinarity
Le postmodernisme à Vincennes : 1968-1980

In the midst of the events of May-June 1968, of the general strike and the student revolts, the Gaullist government accedes to the students’ demand by creating a new university on the very model they demand. Interdisciplinary, open to the workers and completely self-governed, this university will be called the Centre Universitaire Expérimental de Vincennes (C.U.E.V.) which will become the home of the French intelligentsia, welcoming, among others, Deleuze, Guattari, Lyotard, and many more within the philosophy department which was founded and directed by none other than Michel Foucault from 1968 to 1970. It is those very conditions which were at the origin of postmodern philosophy, conditions from which a new theory and a new practice of philosophy will emerge: Vincennes philosophy. The goal of this thesis is to describe and determine this philosophy. How it is that it stands the origin of postmodernism? In order to respond to this question, this thesis is divided into three parts following three distinct of approaches: historical, pedagogic and philosophical. I) The historical part will follow the history of Vincennes while looking for the chronological development of the new philosophy as well as the historical events which contributed to its birth. We will follow the story of the University from its creation in 1968 to its destruction by the Mayor of Paris, Jacques Chirac, in 1980. II) The pedagogic part will focus on the teaching innovations of Vincennes and on the impact they had on the various philosophers who taught there. Those innovations include: 1) the creation of the Value Units (VU) ; 2) interdisciplinarity ; 3) the combination of research and teaching ; 4) self-government and 5) workers’ admission. III) the philosophical part, the longest, will discuss aspects common to the aforementioned three philosophers (Foucault, Deleuze, Lyotard). That is to say, the critique of the modern conception of man as 1) free and 2) rational, and the critique of the modern notion of progress. 1) Freedom will no longer be considered a dimension of man who is henceforth seen as determined by his bodily drives and impulses (a heritage of Freud and Lacan) and by superstructures (the heritage of Marx and Althusser). 2) Rationality no longer typifies the essence of man either; the philosophers examined critique those who use rationality as a norm to punish those who deviate from it, especially in Deleuze’s Anti-Œdipus, or in Foucault’s Madness and civilization. 3) The notion of progress, a common idea in modern philosophy, will also be criticized, especially through the critical analysis of metahistorical narratives, as found in Lyotard, for example. The goal of these three approaches is to uncover the essence of Vincennes philosophy and with it, postmodernism, which is to say, that of contemporary philosophy.

Keyphrases: Vincennes, Philosophy, Postmodernism, Poststructuralism, Education
Rôle de HMGB1 à l’interface materno-fœtale

Sterile inflammation, caused by endogenous damaged-associated-molecular-patterns (DAMP), at the maternal fetal interface is frequently observed in pregnancy complications and leads to placental inflammation and dysfunction by unknown mechanisms. HMGB1 has been associated to preeclampsia, preterm birth and it can be released in the extracellular space and associated to increased inflammatory actions. Extracellular HMGB1 has two isoforms, (HMGB1-disulfide-D) inducing proinflammatory cytokines whilst the other (HMGB1-reduced-R) acts as a chemoattractant. The role of HMGB1 and its isoform at the maternal-fetal interface is mostly unknown. The objective of my master was to investigate the roles of HMGB1 at the maternal-fetal interface including its subcellular localisation during trophoblast differentiation and pro-inflammatory effects on the placenta. Methods: Term placental explants were used to determine the subcellular localisation of HMGB1 during trophoblast differentiation or treated with specific HMGB1 isoforms (HMGB1-D or HMGB1-R) to determine the impact on inflammation and placental function. Alongside, placentas from women with either normal term pregnancies, PE or PPPE were used to determine the distribution of HMGB1 and its receptor. Results: HMGB1 subcellular localisation is modulated during the syncytialisation process with major cytoplasmic and extracellular localisation to a more nuclear localisation in differentiated trophoblasts. Promoting HMGB1 nuclear export, using the histone deacetylase inhibitor (HDAC) NaB, increased HMGB1 cytoplasmic concentration leading to increase secretion of human chorionic gonadotropin (-hCG) in placental explants. HMGB1-D treatment of explants led to the secretion of pro-inflammatory cytokines (IL-1, IL-6 et MCP-1) and impacted trophoblasts differentiation observed by decreased -hCG secretion. In pathological conditions, HMGB1 and his receptors, RAGE and TLR4, expression is increased in PPPE compared to non-pathological pregnancy. To conclude, we demonstrated changes in the localisation of HMGB1 in association with trophoblast differentiation in uncomplicated pregnancies. Cytoplasmic accumulation of HMGB1 is the first step before its release in the extracellular space. We showed that a specific isoform of HMGB1 (disulfide isoform) induced inflammatory cytokines secretion which suggests a role of this DAMP in placental inflammation and function. Finally, HMGB1 and its receptors are increased in a pathological condition (PPPE) demonstrating that this DAMP may play different role in both inflammatory context and trophoblast differentiation.

Keyphrases: HMGB1, Placenta, syncytialisation, placental dysfunctions, pregnancy complications, preeclampsia, subcellular localisation
Recommandations d’experts pour une intervention sur l'alimentation intuitive pour les adolescents québécois

Food is an integral part of our lives. Humans rely on it to survive. The impact of our food choices on our health has led to many nutritional recommendations. Intuitive eating is a novel approach that strives for a healthy relationship with food. Its 10 principles favor the consideration of hunger and fullness signals, understand the impact of emotions and thoughts on food choice and behavior, and explore the roles of body image and physical activity on overall health. This study aims to obtain experts’ recommendations to facilitate intuitive eating in adolescents in Quebec. Using the Delphi method, expert nutritionists in the topic will be consulted and react to each other’s comments, allowing a consensus to emerge on the questions addressed within the study.  The results indicated the importance of each principle and the relevance of adapting the approach according to the participants’ ages. An optimal duration of 45 to 60 minutes was expressed, as was the necessity of having multiple sessions (weekly to monthly frequency).  Participants’ experimentation of the principles and training for the instructor were deemed particularly important and special attention must be paid to the language used. The experts also confirmed the many applicable contexts, from the school context to clinical environments, as well as the multiple possibilities for interventions, from interactive discussions to tasting sessions and cooking lessons. The effects that are expected ranged from a heighted recognition and confidence in their hunger and fullness signals, a rise in their permissiveness in their food choices and an evolution towards an eating pattern responding to their physical rather than emotional needs. These results agree with studies done with intuitive eating in the adult population, studies with food disorders as well as with the few studies done in the school setting. However, this study adds information on how to use intuitive eating precisely with Quebec adolescents. Additional research is necessary to validate the experts’ recommendations, such as in an experimental study. Also, research into the type of vocabulary to employ would be of use to the instructors themselves.

Keyphrases: Adolescents, Delphi, Intuitive eating, Obesity, Health promotion
Fonction de la glycoprotéine Golgi apparatus protein 1 (GLG1) dans la différenciation des adipocytes et l'effet de la forme de type sauvage et la forme tronquée de GLG1 sur le métabolisme des lipides

Golgi apparatus protein 1 (GLG1) is a 160 kDa transmembrane protein interacting with apolipoprotein B100 (apoB100), low-density lipoprotein receptor (LDLR) and proprotein convertase subtilisin/kexin type 9 (PCSK9). However, the protein’s posttranslational regulation and mechanism of action are poorly understood. Previous studies showed that GLG1 is cleaved resulting in two fragments of 150 kDa and 55 kDa secreted at the cell surface and in the extracellular matrix. The first objective of this study is to identify enzymes responsible for GLG1 proteolysis and the effect of cleavage on its function in lipid metabolism. Furthermore, our collaborators showed that mice with GLG1 knockout have a higher number of adipocytes, but those cells are smaller in size compared to those in wild type mice. Therefore, the second objective of the study is to measure the variation of GLG1 expression during adipocytes differentiation and to identify the effects of GLG1 knockout on adipocytes differentiation. For the first objective, HEK293T cells overexpressing GLG1 were either transfected with basic amino acid-specific proprotein convertases (PCSK) or treated with enzyme inhibitors. Media and cell lysates were analyzed by Western blot. No new fragments were detected in media of PCSK-transfected cells. Cell treatment with trypsin-like serine proteases inhibitors, AEBSF and Gabexate mesylate, reduced the secretion of the 55 kDa fragment. To identify the metalloproteinase responsible for GLG1 shedding, GLG1 was co-transfected with Tissue Inhibitors of Metalloproteinase (TIMP1-4). Our results showed that TIMP3 inhibits shedding of the 150 kDa fragment. Finally, wild-type mouse plasma was analyzed by Western blot and showed the presence of both fragments in vivo. For the second objective of the study, fibroblasts 3T3-L1 cells were differentiated into adipocytes and GLG1 mRNA and protein expression were measured at day 0, 2, 4, 6, 8 and 10 by qPCR and Western Blot. Our results showed that GLG1 expression increased during differentiation and a peak was observed at day 4. To conclude, in the first objective of our study, our results showed that trypsin-like enzymes cleave GLG1 and produce a 55 kDa fragment. Shedding of GLG1 is inhibited by TIMP3, which suggests that ADAM10 or ADAM17 are involved in the release of the 150 kDa fragment. In addition, both 55 kDa and 150 kDa fragments were found in normal mouse plasma supporting the relevance of our findings in vivo. In the second objective of our study, GLG1 expression increased during adipocyte differentiation suggesting a role in adipose tissue development and/or morphology. In conclusion, our study will help elucidate how proteolysis of GLG1 impacts its role in the regulation of apoB and PCSK9 secretion and lipid metabolism and how can GLG1 expression affect adipocytes differentiation.

Keyphrases: Trypsin-like, differentiation, GLG1, Golgi apparatus protein 1, ESL-1, apoB100, CFR, TIMP3, PCSK9, LDL-C, adipocytes
Les longs cycles de Kondratiev et l’évolution de l’industrie du tramway au Canada (1861-2021)

This dissertation is an attempt to structure the history of the streetcar industry in Canada. The object is studied as a whole in order to identify and analyze its periodization. The last major attempt was made in 1966, when Due completed its research by focusing solely on the Canadian intercity streetcar industry (Due 1966); thus excluding horse-drawn and city streetcars. Since then, we have seen the emergence of the light rail system (LRT). These are currently being deployed or redeployed in many Canadian cities. This is why we felt it was appropriate to shed new light on the subject.   Our goal is to go beyond anecdotes, case studies and thematic stories by using operational and financial data compiled for each of the networks across Canada. We analyzed the evolution of the tramway industry in Canada, following the Kondratiev long cycle concept, from horse-drawn streetcars to LRT. We have superimposed Schumpeter's Creative Destruction approach to demonstrate the legacies of earlier technologies, and the use of these technologies for new cycles.  As we have shown, electric streetcars have brought about a significant paradigm shift that has changed the face of urban and interurban transit, leading to the deployment of vast networks and the demise of animal-drawn streetcar systems. However, as predicted by Kondratiev's theory of long cycles and the downward trend in the profit rate, the industry encountered obstacles that proved too difficult to overcome. This led to the collapse of the electric tramway, which paved the way for new technologies, better adapted to today's needs. When the privately operated light rail industry was no longer viable, the state intervened.

Keyphrases: Horse-drawn streetcar, Electric streetcar, Light rail system (LRT), Transport history
La racialisation des musulman.es au Québec : analyse d’un cas de diffamation à caractère islamophobe

This dissertation examines the process of racialization of people of Muslim faith and/or culture. It seeks to shed light on the way in which this racialization is exemplified with regard to Muslims who participate in the political and social debates within their society (more precisely, the debates concerning secularism and religious symbols). The scientific approach adopted in this dissertation combines individual experience and sociological analysis. In the case being studied, the participation by the author of this research in a public debate in Quebec, in 2013 and 2014, surrounding a bill on State secularism and religious neutrality (Bill 60) gave rise to a smear campaign targeting her and culminating in legal action. Since the target of this campaign was Muslim, the defamation drew on conspiracy tropes of Islamisation and the infiltration of democratic institutions and of civil society organizations by Muslims living in Western societies. By studying a case such as this it is possible to observe, by a kind of magnifying effect, the crystallisation of several properties of racialization as it is exemplified with regards to Muslims. The analysis in this dissertation employs videos and posts published on a blog that was active in 2013 and 2014 that peddled in anti-Muslim conspiracy theory, documents from the legal file (defamation suit), as well as a narrative reconstruction of the events.

Keyphrases: islamophobia, racialization, conspiracy theories, defamation, religious symbols, debate
Identification et activation des cellules souches neurales quiescentes dans le cerveau adulte et durant le vieillissement

Neurogenesis is maintained in restricted regions of the adult brain called neurogenic niches. One of the main neurogenic niches is the ventricular-subventricular zone (V-SVZ) in which neural stem cells (NSCs) reside. NSCs produce neurons through the generation of transit amplifying progenitors and neuroblasts. Recent studies on adult neurogenesis revealed the existence of quiescent NSCs (qNSCs, also called B1) and activated NSCs (aNSCs). The current model of adult neurogenesis places qNSCs (B1) upstream of aNSCs in the lineage. The hypothesis is that the qNSC population constitutes a “reserve” pool to maintain aNSC pool throughout life.  So far, the techniques used do not allow specific targeting of the qNSCs in vivo. Therefore, it is not possible to analyze their biological properties, activation mechanisms and relationship with aNSCs. This understanding is also necessary to establish therapeutic strategies that could utilize the potential of stem cells to restore neurogenesis in contexts of aging and neurodegenerative diseases. In order to characterize qNSCs in the ventricular zone, we took advantage of plasmid electroporation in a reporter mouse model, Rosa26-stop-EYFP. In this model, the sequence coding for EYFP preceded by a floxed STOP codon is inserted at the Rosa26 locus. Excision of the STOP codon by a recombinase enables expression of the reporter in electroporated cells and their progeny. This technique enabled the specific targeting of a ventricle-contacting astrocytes population and to study their contribution to adult neurogenesis. Unlike transgenic or viral approaches, electroporation can target quiescent cells and the expression of the plasmid is restricted to the ventricle-contacted cells. Using this approach, we made surprising observations: i) this population is mostly quiescent and only minimally contributes to adult neurogenesis, ii) this population does not participate in niche regeneration in vivo and iv) their neurogenic output can be increased by expressing the pro-neural gene Mash1. Next, we investigated the role of EGFR signaling in the regulation neural stem and progenitor cells (NSPCs) activity. In this second study, we show that i) EGFR signaling decreases during aging, ii) PI3K/AKT, MEK/ERK and mTOR exert different regulation proliferation, differentiation and survival of NSPCs and iii) activation of EGFR in the qNSCs increases V-SVZ neurogenesis in 3-months-old animals but not in 6-months-old or Alzheimer’s disease model animals. Our data suggests that the NSC population is heterogeneous, with variable neurogenic output from the different sub-populations, as well as different activation modalities. We also showed that EGFR-associated signalling pathways differentially regulate NSPCs activity. Finally, our results indicate that the factors present in the V-SVZ niche during aging dominantly inhibit activation of NSCs.

Keyphrases: Cellule souche neurale, EGFR, AKT, ERK, mTOR, Neural stem cell, Neurogenesis, Ventricular-subventricular zone, Aging, Electroporation
FASN mutations in epileptic encephalopathies

Fatty Acid Synthase is a large protein complex encoded by the FASN gene, which is responsible for de novo lipogenesis from acetyl-CoA and malonyl-CoA in the presence of NADPH. The endpoint of this process is the production of palmitic acid. The roles of fatty acid synthase in embryonic development are well established: it is ubiquitously expressed in early embryos, particularly in tissues undergoing active proliferation, outgrowth, and remodelling, and it is thus essential for normal brain development and neuronal function. Consequently, FASN gene mutations have been associated with several neurodevelopmental conditions, including autism spectrum disorders (ASD). Recently, the laboratories of Drs. E. Rossignol and P. Campeau at the CHU Ste-Justine (Université de Montréal), with their international collaborators, have identified 10 patients with neurodevelopmental disorders (i.e., developmental delay, intellectual disability and/or epilepsy) carrying recessive or de novo mutations in the FASN gene, supporting a critical role of FASN in regulating neuronal circuit development and function. However, the mechanisms by which mutations in the FASN gene result in epilepsy are unknown. We postulate that FASN mutations alter palmitic acid synthesis and disrupt neuronal network development, resulting in network hyperexcitability and epilepsy. In this study, we expand the phenotypic description of patients carrying FASN mutations, while generating a novel mouse model carrying a patient-derived FASN mutation to explore the underlying cellular and network mechanisms. Our data reveal that FASN mutations, in humans, generate neurodevelopmental disorders characterized by epilepsy, global developmental delay (GDD), intellectual disability (ID), and a broad range of neurological signs (motor deficit, spasticity, hyperreflexia, hypotony, and ataxia). In our knock-in FasnS154N mouse model, homozygous mutations resulted in prenatal lethality. In contrast, heterozygous mutations caused a clinical phenotype reminiscent of the patient phenotype, with anxiety-like behaviors, spontaneous interictal spikes on electroencephalograms (EEG), and a tendency to a reduced PTZ-induced seizure threshold. We discuss the potential underlying mechanisms, including an altered FAS activity within the prefrontal cortex and the amygdala, aberrant palmitoylation of postsynaptic density proteins, the vulnerability of dentate gyrus granules cell, altered neural stem cells activity and neurogenesis, improper axonal growth and myelination, resulting in altered neuronal excitability and synaptic function, aberrant network activities and epilepsy. These mechanisms will be explored in subsequent studies using our novel animal model.

Keyphrases: FASN gene, palmitic acid, epileptic encephalopathy, epilepsy, autism