NCube/papyrus huggingface dataset:
New insights on ammonia metabolism in endothelial cells of the blood brain barrier

Hepatic encephalopathy (HE) is a complex neuropsychiatric syndrome, which is a major complication of liver disease. Cytotoxic edema is a serious complication of HE, known to be the result of astrocyte swelling. Blood derived pathogenic factors such as ammonia (NH4+) and oxidative stress’ (OS) are known to be synergistically implicated. Endothelial cells (EC) of the blood brain barrier (BBB) are the first cells regulating passage into the brain and to contact blood-derived molecules. The effect of ammonia and oxidative stress on EC transport and metabolism has never been thoroughly explored. Therefore, our aim was to evaluate the effects of NH4+ and reactive oxygen species (ROS) on EC of the BBB using in vivo and in vitro models systems. The Na–K–2Cl cotransporter (NKCC1) has been demonstrated to be involved in the pathogenesis of brain edema in numerous neurological conditions. NKCC1 can transport NH4+ into the brain and is regulated by ROS. Therefore, the expression of NKCC1 was evaluated in primary EC submitted to different concentrations of ROS and NH4+ as well as in cerebral microvessels (CMV) isolated from the bile-duct ligated (BDL) rat, a model HE induced by chronic liver disease. No upregulation of NKCC1 was present in either the treated EC or CMV. Glutamine synthetase (GS) is an enzyme with an important compensatory role in NH4+ detoxification during liver disease. GS is expressed in muscle and brain (astrocytes) but has never been thoroughly explored in ECs of the BBB. GS protein expression and activity was found in EC of the BBB in vitro (primary EC) and in vivo (CMV isolated from naive rats). In the BDL model, GS expression in CMVs was not significantly different from SHAM-operated controls. In addition, we treated ECs with conditioned medium from plasma of BDL rats and found a decrease in GS protein and activity when compared to SHAM. Furthermore, EC treated with NH4+ increased GS activity while treatments with ROS with and without NH4+ decreased GS activity. Overall these results demonstrate for the first time that GS is present in EC both in vivo and in vitro. GS is downregulated in EC treated with BDL plasma (but not in BDL CMV). Interestingly, NH4+ stimulates GS activity in ECs, while ROS inhibits GS activity, possibly justifying the results found from the conditioned medium studies. We speculate that ROS prevents the upregulation of GS in the BBB, decreasing the capacity of the EC to detoxify ammonia and to limit ammonia entry into the brain. We foresee that upregulating GS in ECs of the BBB could become a new therapeutic target for HE.

Keyphrases: Hepatic encephalopathy, Hyperammonemia, Endothelial cells, Brain edema, Glutamine synthetase, NKCC1
Le rôle protecteur de la périlipine 2 dans la cardiomyopathie diabétique

The accumulation of lipids in the ER alter its functions and homeostasis which triggers a signalling pathway called ER stress (ERS). This pathway is initially programmed to recover ER homeostasis, but prolonged, it triggers an apoptosis cascade. Absorbed lipids are routed to the ER where they are converted to diacylglycerides (DAGs) and triacylglycerides (TAGs) which are packaged into lipid droplets. Lipid droplets contain a core of TAG and cholesterol esters which are converted by a phospholipid monolayer with associated proteins. In our laboratory, we are interested in investigating the mechanisms of lipotoxicity in the setting of diabetic cardiomyopathy.  We demonstrated that palmitate, the most abundant saturated fatty acid in the human diet, triggers ERS in H9c2, a cardiomyoblast cell line. This stress is accompanied with a lack of lipid droplets, accumulation of DAGs in the ER, and followed by a high mortality of cells via the activation of an apoptotic pathway. Moreover, palmitate causes the degradation of Plin2, a partial reduction of Plin3 expression, while Plin5 is intact. In contrast, oleate, the most abundant mono-unsaturated fatty acid in human diet, induces the formation of abundant lipid droplets but does not cause ERS nor DAG accumulation in the ER compartments. Plin2 degradation is also a result of ERS inducers that are independent of lipids associated mechanisms like tunicamycin and thapsigargin. The lack of Plin2 in these two conditions has no effect on the lipid droplets formation nor on the TAG synthesis. On the other hand, inhibition of proteasome slightly protected Plin2 and reduced the palmitate-associated cell death. Moreover, the co-administration of oleate with palmitate reduced the cell death and induced Plin2 expression, both in an oleate dose-dependant way. Finally, overexpressing Plin2 reduces palmitate-associated ERS and cell death. In brief, Plin2 plays a protective role against ERS. This mechanism seems partially independent of lipids which is a novel function of Plin2.

Keyphrases: Diabetic Cardiomyopathy, Lipotoxicity, ER stress, Lipid Droplet, Perilipin 2
De la propriété de soi à un concept égalitariste de la propriété

The purpose of this thesis is to try and undermine the libertarian project of defending the liberal structure of ownership through its use of the principle of self-ownership. Far from denying the concept of self-ownership, we adopt the principle associated with libertarian thought and show that the adoption of such a principle leads us to a restructuring of the concept of ownership towards one that is coherent with egalitarian and democratic values. We hope that, by doing so, we are able to show the incoherence within libertarianism and give the tools necessary for egalitarians to defend their ideas on libertarian grounds.

Keyphrases: John Locke, Taxation, Property, Liberal Ownership, Self-Ownership, Libertarianism, Left-Libertarianism, Egalitarianism, Money
Michel-Ange et le motif des genitalia : signification, perception et censure

We propose a study on the male genitalia in Michelangelo’s production, in order to grasp the significance in different works of art depending on the subject that they represent. By focusing on four pieces of art of the Florentine artist, we would like to clarify the visual impact of the male genitals unveiled and the perception from the Italian audience of the fifteenth century and sixteenth century. The Bacchus (1496-1497), The David, (1501-1504), The Risen Christ (1519-1520) and The Last Judgment (1536-1541) have been chosen for the variety of the topics they illustrate and for the different contexts of production and exhibition. We compare religious pieces of art to profane pieces of art to identify specific issues that result in every case. The decision to stick to only Michelango’s artistic production also implies looking at a specific type of male figure, directly inspired by the Antiquity.   For a better understanding of what results from the genitalia’s unveiling, we define essential notions like nude, nudity, sexuality, masculinity and virility in the Renaissance. With a historiographical approach based on The Sexuality of Christ in Renaissance Art and in Modern Oblivion, written by Leo Steinberg, we support his hypothesis about the representations of Christ’ genitals. And with a historical approach we suggest some hypotheses about the nudity of iconic figures realised by Michelangelo.  By focusing mainly on the pieces of art mentioned above and the detail of genitalia, we notice that artists, such as Michelangelo, did not represent this detail by chance, but because this part of the body is rich of signification and can serve to express many concepts.

Keyphrases: Genitalia, Censure, Art history, Italian Renaissance, Michelangelo, Nakedness, Masculinity, Virility, Censorship, Counter-Reformation
La critique romantique face au Moyen Âge : La Harpe, Villemain, Nisard et Sainte-Beuve

The nineteenth century rediscovered, in a context of rupture with the Ancien Régime's aesthetic, the middle Ages' literature and its prolongations. That literature has been received in different ways, according to the position of each critic in the quarrel of the romantics. This quarrel thus modulated the reception of the works from before the XVIIth century: those became an example to follow for some; or were only, for others, mere examples of the French civilisation's childhood. That new taste of romantics for works neglected by the two preceding centuries brought a questioning about the literature in general, in a new perspective of its historicity. From now on, literature had to be regarded as an expression of a particular and ever changing civilisation. In this context, a new discipline appeared soon: the history of French literature; history still mixed with subjective evaluations and didacticism. We'll delve therefore on the reception that the literature before the XVIIth century received from the most famous and the most representative critics and historians of the nineteenth century, i.e. La Harpe, Villemain, Nisard and Sainte-beuve. We'll study how the literary doctrines of each critic influenced theirs judgements; and will see how the Middle Ages' works has been sometimes used to defend the aesthetic contentions of its judges. We'll analyse as well the variety of the judgements that happened to occur over the years within the framework of a same trend.

Keyphrases: La Harpe, Villemain, Nisard, Sainte-Beuve, Middle Ages, Romanticism
Le poids des préjugés dans trois romans Kettly Mars

This master’s thesis studies how the prejudices of the haitien social space affect the text layout in three Kettly Mars’s novels: Kasalé, L’heure hybride and Saisons sauvages.  These prejudices defend by the bourgeoisie represent an elite culture which values French language and a western inheritance and despises the popular culture, impregnated with an African inheritance and characterized by the practice of vodoo and the Creole language. “The colour prejudice”, described by certain authors as the base of the system of social organization, also takes an important place within the social discourse.   The three studied novels take place during the political regime of Duvalier: François Duvalier governs in Kasalé and Saisons sauvages and Jean-Claude Duvalier governs L’heure hybride. The presence of dictatorship affects the treatment of the prejudices in Kettly Mars’s novels especially because François Duvalier exploited the Haitian bourgeoisie’s prejudices in his political rhetoric by claiming to be a defender of Haitian popular culture. Nevertheless, Kettly Mars’s novels illustrate the way the dictatorship reproduces these prejudices. With the sociocritic’s notions of “discours social” and “imaginaire social”, this study will question the text layout of the prejudices on the skin color, the popular culture (which includes voodoo and Creole) and the sexuality and the sexual roles through stereotypes, social representations and languages in novels.

Keyphrases: Kettly Mars, Haitian novel, prejudices, sociocritic
Sentiment de justice chez les personnes victimes : le rôle de l'information et du contact humain

Victims’ needs are numerous and have been repeatedly listed as needs of information, reparation, psychological support, status within the criminal justice system, protection and practical needs. With procedural and interactional justices as background, information and human contact are assessed in terms of responding to the victims’ needs. The sample represents 188 victims in the Quebec legal process between December 2003 and March 2004. Information on support services and contact with those services are, in bivariate level, directly related to the sense of justice. At the finish line, however, the multivariate level tells us that information about the investigation remains the only variable related to this sense of justice. Finally, in terms of human contact, contact with the Crime Victims Assistance Centers (CAVAC) and sustained contact with the police are important variables.

Keyphrases: Information, Victims’ needs, Sense of justice, Human contact
Deciphering causal genetic determinants of red blood cell traits

Genome-wide association studies (GWAS) have revealed several genetic variants associated with complex phenotypes. This is the case for red blood cell (RBC) traits, which are particularly amenable to GWAS as they are routinely and accurately measured. Understanding RBC trait variation is important given their significance as clinical markers and modifiers of disease severity. Notably, increased fetal hemoglobin (HbF) production in sickle cell disease (SCD) patients is associated with a higher life expectancy and decreased morbidity. Nonetheless, most variants identified through GWAS fall in non-coding regions of the human genome, increasing the difficulty of identifying causal links.    The main goal of this project was to identify and characterize genes influencing complex traits, and in particular RBC phenotypes. First, I developed an approach to identify and test potential gene knockouts affecting anthropometric traits in a large sample from the general population, which did not yield significant associations. Then, I characterized the DNA methylome and transcriptome of erythroblasts differentiated ex vivo from hematopoietic progenitor stem cells (HPSC), and identified several genes potentially implicated in fetal and adult-stage erythroid programs. I also identified microRNAs (miRNA) that show specific developmental expression patterns and that are enriched in inversely expressed targets. Finally, I mapped expression quantitative trait loci (eQTL) in erythroblasts, and identify erythroid-specific eQTLs for ATP2B4, the main calcium ATPase of RBCs. These genetic variants are associated with RBC traits and malaria susceptibly, and overlap an erythroid-specific enhancer of ATP2B4. Deletion of this regulatory element using CRISPR/Cas9 experiments in human erythroid cells minimized ATP2B4 expression and increased intracellular calcium levels.    In conclusion, large and comprehensive genotyping datasets will be necessary to test the role of rare gene knockouts on complex phenotypes. The transcriptomes and DNA methylomes of erythroblasts show substantial differences correlating with their developmental stages and that may be implicated in HbF production. These results also suggest a strong implication of erythroid enhancers and miRNAs in developmental stage specificity.  Finally, characterizing the erythroid-specific enhancer of ATP2B4 suggest that integrating epigenomic, transcriptomic and gene editing experiments can be a powerful approach to characterize non-coding genetic variants. These results implicate ATP2B4 in erythroid cell hydration, which is associated with malaria susceptibility and SCD severity, suggesting that therapies targeting this gene could impact diseases affecting millions of individuals worldwide.

Keyphrases: Sickle cell disease, Malaria, Red blood cell traits, Genome editing, Malaria susceptibility, Genome-wide association studies
Rôle des Smads lors du processus de régénération chez Ambystoma mexicanum

Since wound healing in human is imperfect and associated with fibrosis, understanding how regeneration works would be a great asset to improve patient’s health. During this PhD project, we have published a paper exposing the weaknesses of certain research models when studying wound healing. Those limitations are even more striking when studying regeneration. This publication sets the stage for the use of the axolotl (Ambystoma mexicanum) as an excellent model to study regeneration and the importance of TGF- for the process. The multifunctional cytokine TGF-β is involved in healing, scarring, cellular differentiation, growth and migration. This cytokine is associated with the near perfect healing of oral tissues in humans, but is also associated with scarring of multiple tissue types. TGF-β is also associated with epimorphic regeneration in echinoderm and liver hyperplasia.  Previous work had shown that treatment of regenerating axolotl limbs with a specific inhibitor of TGF-β canonical signalling (SB-431542) prevents regeneration (Lévesque et al., 2007). Since canonical signaling goes through Smad2 and Smad3, those two proteins are at the center of the second publication. During limb regeneration, Smad2 is phosphorylated at 6h-48h post-amputation (pa), which corresponds to the cellular migration phase and the beginning of the proliferative phase. On the other hand, Smad3 phosphorylation happens earlier (3h-6h pa), while the total protein expression is lower. Treatment with SB-421543 blocks the phosphorylation of both Smad2 and Smad3. No blastema is formed, but the wound closes at the same rate. Treatment with other inhibitors, SIS3 or Naringenin (specifically targeting Smad3), blocks approximately 50% of Smad3 phosphorylation (as determined by western blotting), but regeneration is not affected. Differential regulation of Smads is essential for proper regeneration to occur. Lastly, we have tried multiple approaches to diminish specifically the activation of Smad2. Using the only axolotl cell line available (AL-1), we have tried inhibition with LNA molecules, long antisense and overexpression of a competitor. None of these approaches specifically reduced the levels of Smad2. In addition, other experiments confirmed that activation of Smad3 during the regeneration process is limited.  The extraordinary ability to regenerate that the axolotl possesses is tightly linked to a differential activation of Smad2 and Smad3 proteins. Smad2 phosphorylation is associated with cellular proliferation and migration, hence blastema formation, while the apparent lack of Smad3 activity might partly explain why these animals do not form scar tissues.

Keyphrases: Axolotl, TGF-β, Smad2, Smad3
Différences de genre dans la dissociation et la détresse péri-traumatique, et associations avec les troubles de stress aigu et de stress post-traumatique chez des victimes d’actes criminels graves

This thesis aimed to contribute to the acute stress disorder (ASD) and post traumatic stress disorder (PTSD) literature in terms of gender differences among crime victims. Precisely, we were interested in the intensity and presence of peritraumatic reactions namely, dissociation and distress, among men and women victims of violent crimes. Two objectives were pursued. First, we evaluated whether peritraumatic dissociation and distress were significant risk factors for ASD development and if these acute stress reactions’ predictive capacity, differed according to gender. A second objective was to investigate if peritraumatic dissociation and distress significantly predicted PTSD development according to gender. Globally, in this research project, we were interested in determining the impact of gender in the prediction of the above-mentioned relationship . Semi-structured interviews; the Acute Stress Disorder Interview (ASDI) in the first article and the Structured Clinical Interview for DSM-IV (SCID) in the second article were conducted with 214 victims (125 women, Mage=39.6yrs) to assess ASD and PTSD respectively. Data on peritraumatic variables were collected through self-report questionnaires, the Peritraumatic Dissociative Experience Questionnaire and the Peritraumatic Distress Inventory.  Peritraumatic dissociation and distress were both significant risk factors for ASD in men and women. Women presented higher peritraumatic distress levels compared to men victims. Gender differences were revealed through past potential traumatic experiences, where they have a cumulative impact on ASD risk development for men, but having few past potential traumas could be a protective factor for women. In the second article, findings reveal that acute stress variables were both significantly related to more PTSD symptoms, although no gender differences were identified. An acute stress disorder diagnosis was also confirmed as an important predictor of PTSD in victims of violent crimes.  These results, study limitations, directions for future research as well as clinical implications for ASD and PTSD treatment will be discussed.

Keyphrases: victims of violent crimes, post-traumatic stress disorder, acute stress disorder, peritraumatic dissociation, peritraumatic distress, gender
Formation de poudres carbonées dans un plasma de haute fréquence produit à très basse pression dans des mélanges acétylène-argon

Dusty plasmas are plasmas that contain solid particles of nano- or micrometer size. They are widespread in the cosmic environment and act as precursors in the formation of planets and stars. Such plasmas are also used in laboratories for the synthesis of nanocomposites, which have wide technological and medical applications. While a large scientific effort has been invested in the study and control of such plasmas, the initial growth mechanism of powders (i.e. before they reach several tens of nanometers) remains poorly known. This work contributes primarily to expand the fundamental knowledge in the field of dusty plasmas. Our goal is to understand the physical chemistry of high-frequency plasmas magnetically confined in chemically reactive gases. In addition, we aim by examining the kinetics of the precursors in the plasma to understand the mechanisms of nanoparticle formation in the volume and to control their characteristics in a magnetically confined low pressure Ar/C2H2 plasma. This contribution has a direct impact on science and plasma applications. Among the applications related directly to this research, we mention the synthesis of carbon-based nanocomposites for their integration in solar cells and biomaterials. By examining the plasma characteristics (plasma temperature and density, cation and anion density) and correlating them to those of the dust particles, we found that the magnetic field changes the process of the formation of these particles in the discharge at very low pressure. Specifically, it stimulates the nucleation of carbon nanoparticles through several channels, i.e. through the anions and cations. These nanoparticles include two different phases, an amorphous carbon layer and a porous core formed of grains aggregate. These grains are formed of graphite nanocrystals coated with an amorphous layer. Moreover, the radius of the dust particles increases with the magnetic field, which is related to the enhancement of their residence time in the plasma volume.

Keyphrases: anions, cations, nanocomposites, dusty plasma, magnetic confinement, low pressure, nucleation, anions, cations, carbon nanoparticles, nanocomposites
Anatomy of smooth integers

The object of the first chapter of this thesis is to review the materials and tools in analytic number theory which are used in following chapters. We also give a survey on the development concerning the number of y−smooth integers, which are integers free of prime factors greater than y. In the second chapter, we shall give a brief history about a class of arithmetical functions on a probability space and we discuss on some well-known problems in probabilistic number theory. We present two results in analytic and probabilistic number theory. The Erdos multiplication table problem asks what is the number of distinct integers appearing in the N × N multiplication table. The order of magnitude of this quantity was determined by Kevin Ford (2008). In chapter 3 of this thesis, we study the number of y−smooth entries of the N × N multiplication. More concretely, we focus on the change of behaviour of the function A(x,y) in different ranges of y, where A(x,y) is a function that counts the number of distinct y−smooth integers less than x which can be represented as the product of two y−smooth integers less than p x. In Chapter 4, we prove an Erdos-Kac type of theorem for the set of y−smooth integers. If !(n) is the number of distinct prime factors of n, we prove that the distribution of !(n) is Gaussian for a certain range of y using method of moments.

Keyphrases: Analytic number theory, Probabilistic number theory, Method of moments, y−smooth integers, Erdos multiplication table problem, Erdos-Kac theorem