NCube/papyrus huggingface dataset:
Identification de nouveaux substrats de la voie Ras-MAP Kinase

ERK1 and ERK2 (ERK1/2) are members of the Ras-dependent MAP Kinase pathway involved in the regulation of cell proliferation, differentiation and survival. While the roles of these MAP Kinases in the control of these functions are now well documented, the mechanisms behind them are often poorly described. Therefore, many effectors downstream of these kinases are still being identified and characterized. To identify new substrates of the ERK1/2 kinases, two large-scale phosphoproteomic studies were performed by our laboratory and allowed us to identify over a hundred new putative substrates. Among these are some alternative splicing regulators. The mechanisms governing the regulation of this process by upstream signaling pathways aren’t quite well understood yet.  The first study within this thesis focuses on the validation of these new substrates of ERK1/2. Namely, we identified and validated that the splicing factors CDK12, RNPS1, MBNL2 and SRPK2 are novel substrates of ERK1/2 by in vitro kinase assay. Regarding the potential role that a regulation of these factors by the MAP Kinase pathway might have, we studied the early stages of differentiation as driven by the expression of the ERK1 kinase in a ERK1/2 DKO embryonic stem cells murine model. We identified 60 alternatively spliced transcripts following ERK1 expression, including those from DNMT3b and delta-catenin expression. We notably observed a decrease in the splicing of the DNMT3b transcript in response to ERK1 activity, leading to an increase in the expression of the enzyme with the exon coding the catalytic domain.  The last part of this thesis revolves around the identification and characterization of beta-catenin as a novel substrate of MEK1/2. Our research suggest that this phosphorylation occurs predominantly on threonine 472 and that this site is important in maintaining the stability of the protein.  This thesis lays the ground work for a global understanding on how the MAP Kinases ERK1/2 regulates alternative splicing on one hand, and also defines a novel element of regulation between the Wnt/beta-catenin and the MAP Kinase pathway by identifying beta-catenin as a new substrate of MEK1/2.

Keyphrases: MAP Kinases, ERK1/2, MEK1/2, phosphorylation, beta-catenin, alternative splicing, embryonic stem cells, cell signaling
La maladie d’Alzheimer : de son origine aux perspectives thérapeutiques

Alzheimer’s disease (AD) is an incurable neurodegenerative disorder affecting major brain functions including memories and motility. Although the familial form of the disease (FAD) is well characterized, the origin of the prominent form (sporadic AD) remains to be elucidated. Aging is the strongest risk factor for developing the disease. Previous results from the lab and others showed that BMI1 is downregulated in the brain with age. BMI1 is a protein member of the polycomb repressive complex 1 (PRC1) which mediates ubiquitination of the histone H2A which leads to gene silencing. As of note, BMI1 heterozygous mice develop, with age, a neurodegeneration resembling to AD pathology. This work shows BMI1 loss in AD brains and AD neurons derived from induced pluripotent stem cells. This reduction is however not observed in patients with FAD or other dementia. BMI1 knockdown using a shRNA or Knockout using CRISPR/Cas9 technology gave rise to a tauopathy and amyloidopathy similar to AD. Mechanistically, BMI1 loss induces a de-repression of MAPT and a stabilization of GSK3b and p53 leading to neurodegeneration. Restoration of BMI1 physiological levels in AD patients provides new therapeutic avenues.

Keyphrases: BMI1, GSK3b, p53, Tau, Amyloïde, Alzheimer’s disease, Amyloid
Law, religion, and physician-assistance to suicide : the roles of christianity in north american judicial dignified death debates

Medical-aid in dying is an assistance provided by a doctor, which enables a patient to end her/his life when her/his medical condition is incurable and when (s)he in excruciating pain. It can take the form of euthanasia or physician-assisted suicide. It is authorized in several countries, which include Canada and several American states.   In Canada and the United States, legal debates on the legalization or decriminalization of physician-assisted suicide have attracted the attention of many religious groups, notably Christian faith groups. These groups, in their capacity as court Interveners and Amici Curiae had attempted to influence court debates in accordance to their religious beliefs. This study aims to analyze the arguments that were raised by these organizations and faith-followers in their factums and briefs.    In Canada, the various religious arguments had maintained a harmonious interpretation of pious values. Thus, in the Rodriguez and Carter cases despite an evolution in the terminology that was employed, religious groups had attempted to encourage the Supreme Court to maintain the absolute prohibition to physician-assisted suicide, without the very nature of these religious values ever being questioned.    In contrast, in the United States, the debates have primarly focused on the history of Christianity's position on suicide and its assistance. Two diametrically opposed interpretations had confronted one another through the analysis of various biblical characters and Christian martyrs. It appears that the constitutional positions on physician-assistance to suicide in the United States were largely dependent upon opponents to medical-aid in dying, who had relied upon a traditional interpretation of the historical evolution of Christianity.

Keyphrases: Constitution, Rodriguez, Carter, Glucksberg, Quill, Physician-assisted suicide, Medical-assisted death, Law, Christianity
Le droit à la mobilité et le droit au développement : une analyse du déplacement systématique des travailleurs qualifiés de la République d’Haïti vers le Canada

The thesis deals with a critical view of the right to mobility which has been elevated to the level of human rights by the Universal Declaration of Human Rights of 1948. Indeed, this right which was supposed to be an essential attribute The development of individuals has ended up playing an economic function for the benefit of the countries of immigration. The latter end up attracting most professionals, academics from the South, to their territory through an instrumentalisation of the right to mobility. The systemic displacement of the trained people is likely to prevent the realization of the right to development in the South. Taking into account the departure of skilled workers from the Republic of Haiti to Canada, specifically to Quebec, we want to show that the implementation of the category "economic immigration of Canadian immigration law" can, from an international perspective, to hold Canada as a host country for violations of international law. More, generally, the idea is to allow the restoration of a balance in the North / South relations through the problem of the qualified migration which has adverse effects on the development of the countries of origin.

Keyphrases: Brain drain, Right of mobility, Right to development, Sustainable development, Skilled workers, Country of origin, Receiving country
L'analyse économique du droit du poste de commissaire de la Ligue nationale de hockey

The use of the economic analysis of law when studying the governance of the National Hockey League reduces human error in the decision-making process.  The National Hockey League is a professional league.  Value maximisation of the League teams and profits are important economic objectives.  As a priority, the League governance must help the team owners to realize these economic objectives.  The economic analysis of law can help the Commissioner and the team owners improve the governance of the National Hockey League in order to achieve the objective of value maximisation. This study analyzes the Commissioner’s position within the governance of National Hockey League.  In the first part, a description of the National Hockey League structure as well as an analysis of the market conditions will be completed in order to outline the flexibility in governance related decisions.  It is important to understand the impact of the regulations established by the Governors of the League related to the team markets.  Further, in the second part, an analysis of the Commissioner’s position will be completed based on the theory of the firm.  The creation of the Commissioner’s position was added to another element of the theory of the firm.  As such, the team owners now assume the role of supervisor while the Commissioner takes care of the daily management of the League.  The Commissioner has an interest in ensuring that the National Hockey League contributes actively to the generation of income for the teams.  There can be situations where the Commissioner as diverging views with the team owners on governance.  Using corporate law, in the third part, solutions will be recommended to better attaint the objective of value maximisation of the League teams in the Commissioner’s decision-making process.

Keyphrases: National Hockey League, Economic Analysis of Law, Theory of the Firm, Agency Theory, Path Dependence, Board of Directors
Contribution à l’éradication des problèmes liés à la polygamie au Canada, au Cameroun et en Côte-d’Ivoire : essai féministe de théorie interdisciplinaire critique des différentes politiques de gouvernance

Polygamy is an old form of marriage but is still relevant today. It is practiced in different ways in different contexts. It is mainly religion and customary practices that are at the root of its perpetuation. Polygamy’s normative framework differs depending on whether we are in Canada, in Cameroon or Ivory Coast. Indeed, it is banned by the Canadian and Ivorian law while in Cameroon it is permitted. In addition to the above states, most international communities condemn polygamy. Regardless of how polygamy is implemented, it always involves a man married to several women. Polygamy is contrary to the principle of gender equality and violates several international instruments such as the Universal Declaration of Human Rights, the International Covenant on Civil and Political Rights, the International Covenant on economic, social cultural Rights, the Convention on the Elimination of All Forms of Discrimination against Women, the African Charter on Human and Peoples' Rights, the Protocol to the African Charter on Human and Peoples’ Rights on the Rights of Women in Africa and the Convention on the Rights of the Child. It also violates certain domestic laws in force in Canada, Cameroon and Ivory Coast. Because it generates many legal, political, socio-economic and health problems, causing consequently enormous injury from the point of view of the condition of women and children, we think States should take all the necessary means to limit its progression, if not completely eradicate it.  This thesis is an essay. It lists the various problems attributed to polygamy in the scientific literature, and presents them in support of an argument against the legalization of polygamy (and against the practices it supports) in the states observed by our study. This thesis is also part of an interdisciplinary approach, because it relates the discipline of law and its formal sources to other knowledge, in order to better argue and convince the reader. It highlights the state of polygamy in the world by emphasizing its justifications and its consequences. It then analyzes the legal framework established by the positive law of Canada, Cameroon and the Ivory Coast, as well as in international law. It also highlights the various problems that polygamy cause to women and children in a feminist perspective. Finally, it reveals that while initiatives have been taken by the States of our study to fight against this phenomenon, much remains to be done to protect women and children from the evils of polygamy.

Keyphrases: dot, succession, divorce, monogamie, Polygamy, polygyny, polyandry, family, woman, child, problem, levirate, sororate, dowry, equality, marriage, monogamy, feminism, essay, interdisciplinary
Les pourparlers précontractuels en droit québécois : de l’opportunité d’une modification du Code civil du Québec à la lumière des récentes réformes française et allemande

Our thesis focuses on precontractual negotiations in Quebec while adopting a comparative approach by using French and German law. The main objective is to defend the idea of a modification of the Quebec Civil Code in order to ensure that the precontractual period is taken more into account. Indeed, there are currently no specific rules related to precontractual negotiations in the general law of contracts. Only few rules can apply if we interprate them in a broader way they are supposed to, such as article 1375 that forces the parties to conduct themselves in good faith at the time the obligation arises. This state of law differs from both French and German legal systems where rules have been drafted to impact the way parties can act while they are negotiating a contract.   Our thesis insists on practical and legal issues that arise from the way the law is actually built in Quebec. Because of the complexification of contracts linked to the internationalisation of exchanges and the multiplication of them, the phenomenon which consists on negotiating a contract appeared to be necessary and became the rule in the matter. It has, at the same time, generated an increasing litigation. According to us, the Quebec Civil Code should contain specific rules about the way people have to behave during precontractual negotiations and how they will be sanctioned if they are disregarded.  In order to do so, our work is divided in a classic way. First, we focuse on the content of important principles and rules that apply during precontractual negociations, such as precontractual freedom and good faith that both benefit from a large legal scope. Then, we question the implementation of theses principles and rules by studying the nature of the accountability faced after a party has violated them but also the nature of the compensation due after a prejudice has been caused by the fault of a former partner.  While we propose solutions to build more efficient rules, we try to preserve the very essence of precontractual negotiations: freedom and loyalty. We hope the outcome will be interresting for readers and will be useful to any other works on precontractual negotiations that are still not so well treated in civil law studies.

Keyphrases: Culpa in contrahendo, Contractual negotiation, Reform, Precontractual negotiation, Good faith, Freedom of contract, Precontractual accountability, Pre-contract, Promise to contract, Information duty
Systématique, biogéographie et diversification du genre Crudia (Leguminosae, Detarioideae)

In the subfamily Detarioideae (Leguminosae), the genus Crudia Schreb. shows an unusual pantropical distribution and high species richness compared to closely related genera. Crudia species, spread throughout South America, West Africa and Southeastern Asia, have been the focus of independent taxonomic studies conducted by several consecutive authors. To date, however, the evolution and biogeographic history of this genus remain poorly understood. We propose a multidisciplinary approach to study this poorly known genus and to improve our understanding of its evolutionary history. First, we conducted a taxonomic revision of Asian species within the genus Crudia, in accordance with the recent revisions of African and American species. We used traditional taxonomic methods by compiling morphological data based on the study of herbarium specimens. From an initial description of thirty five species from the literature, we retained fourteen species and synonymized the others except for one we consider as a doubtful species. A newly described species was also added. Species geographic distributions were reevaluated and new conservation statuses were suggested. Second, we established a conceptual framework to study the evolution, biogeographic history, and relationship between species of this genus. We sequenced five nuclear regions (ITS, ETS, AGT1, CALTL, and AIGP) on numerous sampled herbarium specimens (K, US, P, L, WAG, U). The phylogenetic analyses resolve Crudia as monophyletic with a well-identified internal structure composed of one clade grouping all Asian species and one clade grouping both African and American species, with the American species grouped in a single clade. Reconstructions of biogeographic history and an associated divergence time analysis calibrated with macrofossils show Crudia originated in Africa during the Eocene and underwent two independent dispersal events during mid-Eocene: from Africa to South America and from Africa to Southeastern Asia. Third, we tested if species richness in the genus Crudia is associated with changes in diversification rates through time and with ecological niche shifts throughout its global distribution. We used species occurrence data, carefully selected to avoid identification errors, associated with environmental data retrieved from the literature. Diversification rates were studied both at the scale of the genus Crudia and the Detarioideae subfamily. We conclude that ecological niches differ from one continent to another and no diversification rates changes were detected in the genus Crudia. Our finding suggest that the greater species richness in Crudia compared to sister genera may be the consequence of relatively older age of this genus.

Keyphrases: Crudia, Detarioideae, Evolution, Diversification, Taxonomic revision, Biogeography, Divergence time, Systematic, Ecological niche
The role of doubt in bulimia nervosa

Bulimia nervosa (BN) is a severe mental health disorder characterized by dietary restriction, the experience of loss of control over eating, and the use of compensatory behaviours. BN, like other eating disorders (EDs), has an elevated rate of comorbidity with obsessive compulsive disorder (OCD) as well as important similarities in terms of phenomenology and clinical features. Pathological doubt, consistently demonstrated as relevant in OCD, represents another cognitive feature potentially shared between OCD and BN. According to the inference based approach (IBA) to OCD, pathological doubt is elicited by a faulty inductive reasoning process termed ‘inferential confusion’. This construct is comprised of two components: the over-investment in possibility-based information and distrust of the senses. Thus, the present study sought to test the role of inferential confusion to BN. Participants with BN (n = 25) and healthy control (HC) participants (n = 25) were recruited.  The first and second thesis articles evaluated the over-investment in possibility-based information component of inferential confusion using adapted versions of the Reasoning with Inductive Arguments Task (RIAT) and Inference Processes Task (IPT), both of which have been validated as analogues of doubt in OCD samples. The Fear of Self Questionnaire (FSQ) was also administered to evaluate investment in a feared possible identity, a construct related to inferential confusion. The BN group demonstrated a pattern of results consistent with an over-investment in possibility-based information on both tasks. The BN group also evinced higher levels of fear of self as compared to the HC group, suggesting over-investment in a feared possible self.  The third thesis article describes the results of a body checking task designed to examine the relationship between perseverative attending to the body and the distrust of the senses component of inferential confusion, operationalized as perceptual confidence. The BN group experienced greater distrust of the senses due to prolonged body checking than the HC group as indicated by decreases in perceptual confidence from pre- to post-body checking. In all three thesis articles, it was found that the results of the experimental reasoning and body checking tasks were correlated with self-report measures of ED symptomatology. This highlights the clinical importance of inferential confusion.  Overall, the results of the present thesis suggest the relevance of pathological doubt elicited by inferential confusion in BN, as well as demonstrate a link between inferential confusion and ED symptomatology.

Keyphrases: Bulimia nervosa, Obsessive compulsive disorder, Inference Based Approach, Inferential Confusion
Modes d’acculturation et cohérence identitaire de jeunes Québécois d’origine chilienne

The consequences of acculturation among immigrants can be felt at various levels, causing confusion, anxiety and depression; these symptoms may even appear in the next generation, the native-born children of immigrants (Berry, 1997). Some studies have shown that the identity crisis experienced by immigrant youth is twofold: the conflict between host and original cultures adds itself on top of the developmental crisis experienced by all adolescents. (Malewska-Peyre, 1993; Moro,  2003; Manco & Godfroid, 2006).  There are currently over 10,000 people of Chilean origin in Quebec. This study aims to understand how young Québécois of Chilean origin face the acculturation phenomenon, what modes of acculturation they use, and to explore the relationship between their modes of acculturation selected, their identity strategies and their psychological adaptation.  In total, 130 young Québécois of Chilean origin participated in this study. Half of young Chileans have adopted the mode of Integration (which implies a strong identification with both the host cultures and their culture of origin) while a third have opted for Ethnocentrism (a strong identification with the culture of origin, but a poor identification with host cultures). On the other hand, when age is divided into two categories, a greater number of older Chileans adopt the Integration mode compared to those who opted for Ethnocentrism (p<0.05). This is true for acculturation in Quebec, but not for Canada. Also, on the differences between the two groups, self-esteem is higher (p<0.01) and their level of psychological distress less (p<0.001). There are no significant differences between the chosen mode of acculturation and the identity dimensions nor the psychological adaptation, except with the Marginalization mode and the Exploration identity strategy, and when the host culture is Canada (p <0.05). The findings that emerge from this study confirm the need to reinforce, in immigration policies, the support and maintenance of the relationship of immigrant children with the culture of their parents' home country.

Keyphrases: Immigration, Acculturation, Youth, Immigration, Acculturation, Chile, Identity strategies, Mental health