NCube/papyrus huggingface dataset:
Activité physique et récompense : impact de la leptine et de la signalisation STAT3 dans les neurones dopaminergiques

Endurance running is rewarding and related to food seeking behaviors. Influence of leptin on voluntary physical activity is well documented from a physiological point of view, but little is known about its hedonic impact. Leptin inhibits the rewarding aspects of food consumption and plays a similar role for other types of stimuli. Leptin binds to the long form of the leptin receptor, situated on dopamine (DA) and GABA neurons of the ventral tegmental area (VTA) in the midbrain. Signal Transducer and Activator of Transcription 3 (STAT3) is an important transcription factor of the leptin signalling cascade.  Phosphorylation of STAT3 is detected only in a subset of neurons that are positive for the leptin receptor, conferring unique properties to DA STAT3 neurons. We generated a mouse model invalidated for STAT3 selectively in dopamine neurons (STAT3DAT-KO).  We first assessed basic metabolic parameters of our model using CLAMS metabolic chambers, including ambulatory acitivity, respiratory exchange ratio (RER) and heat production. STAT3DAT-KO are hyperactive as seen by a higher locomotor activity, but there is no inter-group variation of RER and heat production, and the weight gain is the same.  A rescue strategy targeting the reinsertion of STAT3 in DA neurons of the mesolimbic system normalizes physical activity of the STAT3DAT-KO - which was previously much higher - to that of the control mice, following free access to a running wheel for a period of 4 weeks. The injection of a psychostimulant (agonist of the type1 DA receptor (D1R), Chloro-APB-Hydrobromide (SKF 82958)) reflects a reduced DA signalling STAT3DAT-KO. A compulsive food seeking test reveals a suppression of sucrose intake in both experimental groups. We demonstrate for the first time that the motivation allied to endurance running, independently of food intake regulation by leptin, is dependent upon a diminished leptin-STAT3 signalling in DA neurons of the midbrain, revealing STAT3 as a key player in the regulation of DA tone and the rewarding properties of physical activity.

Keyphrases: Dopamine, Leptin and STAT3, Physical activity, Running, Reward, Ventral tegmental area
Proscillaridin A effects on histone acetylation and C-MYC degradation in acute lymphoblastic leukemia

Acute lymphoblastic leukemia (ALL) represents approximately 25% of all pediatric cancers diagnosed every year. In about 80% of cases, pediatric patients will attain a 5-year event-free survival. Unfortunately, patients who are resistant to treatment or who relapse have a poor prognosis. Hence, novel therapeutic approaches are necessary to increase survival rates. Epigenetic alterations, such as DNA methylation and histone modifications, are involved in disease development, progression, and in particular, resistance to treatment. These reversible alterations represent novel targets in ALL. We recently discovered candidate epigenetic drugs in FDA-approved drug libraries. We performed a secondary screen to test the activity of these drugs in a panel of cancer cell lines. We found that a cardiac glycoside, called proscillaridin A, had anticancer specificity against pediatric leukemia cell lines. Thus, we hypothesize that proscillaridin A has some drug repositioning potential in pediatric ALL. To characterize its epigenetic mechanism of action, we treated two ALL cell lines Nalm-6 (pre-B ALL) and Molt-4 (T-ALL) in vitro for different time points (2-96h) with clinically relevant concentrations of proscillaridin A and analyzed cell growth, cell cycle, gene expression and chromatin modifications. We observed dose-dependent growth inhibition in both cell lines, where 50% of growth inhibition (IC50) was obtained at 3.0 and 2.3 nM in Nalm-6 and Molt-4, respectively. Our results using BrdU staining indicate a cell cycle block in the G2/M phase. By western blot, we detected significant decreases in histone 3 acetylation levels (H3K14ac, H3K9ac, and H3K27ac). Decreases in histone acetylation were associated with a significant reduction in histone acetyltransferase expression (CBP, P300 and TIP60) as well as the CMYC oncogene. By RNA sequencing and gene set enrichment analysis, we observed an upregulation of apoptosis and cell differentiation genes, as well as a decrease in cell proliferation and C-MYC target genes. These promising results illustrate the potential of using the cardiac glycoside proscillaridin A as a novel drug in treatment of relapsed or refractory ALL.

Keyphrases: Acetylation, Oncogene, Leukemia
Étude du rôle de la membrane basale spécialisée dans la maturation de l'émail

The epithelial ameloblasts are separated from the maturing enamel by an atypical basement membrane (BM) that is enriched in laminin 332 (LM-332). This heterotrimeric protein (α3, ß3 and γ2 chains) provides structural integrity to BMs and influences various epithelial cell processes including cell adhesion and differentiation. Mouse models that lack expression of individual LM-332 chains die shortly after birth. The lethal phenotype of laminin γ2 knockout mice can be rescued by human laminin γ2 (LAMC2) expressed using a doxycycline-inducible (Tet-on) cytokeratin 14 promoter-rtTA. These otherwise normal-looking rescued mice exhibit white spot lesions on incisors. We therefore investigated the effect of rescue with human LAMC2 on enamel maturation and structuring of the atypical BM. The maturation stage enamel organ in transgenic mice was severely altered as compared to wild type controls, a structured BM was no longer discernible, dystrophic matrix appeared in the maturing enamel layer, and there was residual enamel matrix late into the maturation stage. Microtomographic scans revealed excessive wear of occlusal surfaces on molars, chipping of enamel on incisor tips, and hypomineralization of the enamel layer. No structural alterations were observed at other epithelial sites, such as skin, palate and tongue. These results indicate that while this humanized mouse model is capable of rescue in various epithelial tissues, it is unable to sustain structuring of a proper BM at the interface between ameloblasts and maturing enamel. This failure may be related to the atypical composition of the BM in the maturation stage and reaffirms that the atypical BM is essential for enamel maturation.

Keyphrases: Laminine γ2, Amelogenesis, Basement membrane, Enamel maturation, Humanized mouse model, Laminin γ2
Rôle de la signalisation Wnt non-canonique dans l’étiologie de l’ostéoarthrose chez l’humain

Clinical and in vitro studies suggest that subchondral bone sclerosis due to abnormal osteoblasts (Ob) is involved in the progression and/or onset of osteoarthritis (OA). Human Ob isolated from sclerotic subchondral OA bone tissue show an altered phenotype, a decreased canonical Wnt/ß-catenin signaling pathway (cWnt), and a reduced mineralization in vitro. Besides the cWnt pathway, at least two non-canonical signaling pathways, the Wnt/PKC and Wnt/PCP pathway have been described. These pathways are activated when a non-canonical Wnt ligand like Wnt-5a binds to a Wnt receptor coupled with non-canonical co-receptors. This activates, respectively for Wnt/PKC-Ca2+ and Wnt/PCP, the phosphorylation of PKC (pPKC) and the phosphorylation of JNK (pJNK) and their effect on downstream targets. However, there are no reports of either pathway in OA Ob. Here, we studied if alterations of the non-canonical pathways could be observed in OA Ob. We prepared primary human subchondral Ob using the tibial plateaus of OA patients undergoing total knee arthroplasty, or from tibial plateaus of normal individuals at autopsy. The expression of genes involved in Wnt/PKC and Wnt/PCP was evaluated by RT-qPCR and their protein production by Western blot analysis, in addition to p-PKC and p-PCP and NFAT and AP-1 activity with luciferase. Alkaline phosphatase activity and osteocalcin levels were evaluated respectively by substrate hydrolysis and ELISA respectively, and mineralization levels were evaluated with Alizarin red staining. OA Ob showed an increased alkaline phosphatase activity and osteocalcin release. The expression of Wnt5a was increased in OA Ob compared to normal. The expression of LGR5 was significantly increased in these cells. Moreover, the expression and production of LGR5 is directly modulated via the stimulation or inhibition of Wnt5a. However, Wnt5a did not stimulate the expression of LGR4. Wnt5a increased the phosphorylation of PKC and JNK as well as NFAT and AP-1 activity. Mineralization levels as well as alkaline phosphatase activity and osteocalcin secretion levels were also linked with changes in Wnt-5a levels. These data indicate that Wnt5a, which is increased in OA Ob, can directly stimulate the Wnt/PKC and Wnt/PCP pathways and this can affect the phenotype and mineralization observed in human OA Ob.

Keyphrases: OA, Ob, Wnt, Wnt-5a, Osteoarthritis, osteoblast, non-canonical Wnt
Understanding the role of CAP proteins in the polarization process of C. elegans

Asymmetric cell division is a crucial step in organism development, as it allows the generation of cellular diversity. In order to achieve asymmetric division cells need to polarize their cell fate determinants and properly orient their mitotic spindle before division. The C. elegans embryo is a powerful and widely used model to study asymmetric cell division. In the embryo the sperm entry site determines the anterior-posterior axis of polarity. In the newly fertilized embryo, shortly after meiosis, the cortex is uniformly contractile and the conserved PAR-3/PAR-6/PKC-3 complex (hereafter referred to as the PAR-3 complex) is localised on the entire cortex. Entry of the sperm triggers posterior smoothening and anterior-directed cortical flows. Asymmetric cortical contractions result in the formation of an anterior domain containing the PAR-3 complex, while the posterior-pole cortex, depleted of the PAR-3 complex, is enriched in PAR-2 and PAR-1 proteins. Therefore PAR domains define an anterior and a posterior pole of the embryo in response to cytoskeleton remodelling. The PAR-4 and PAR-5 proteins remain localized uniformly throughout the embryo. Intriguingly, the PAR proteins exert a feedback regulation on cortical contractility. PAR-5, one of the lately identified PAR proteins, was shown to be an ortholog of the adaptor protein 14-3-3 and to play an important role in cortical contractility. Despite its central role in cortical contractility and henceforth the polarization process, little is known on how PAR-5 regulates cortical contractility. The aim of this project is to better understand the regulation of cortical contractions via the PAR-5 protein and its interactors, and how they control cell polarity. In a GST pull down assay we identified several new interactors of PAR-5. Among these we found CAP-2 (actin capping protein), which was also pulled down with 14-3-3 in three different model systems. CAP-2 has been implicated in actin regulation. Interestingly we found that depletion of CAP proteins by RNA interference in wild type worms results in increased embryonic lethality, suggesting an important role in embryonic development. Live imaging of embryos depleted of CAP proteins shows that these embryos have decreased cortical contractions with a less stable pseudo cleavage furrow, indicating a defect in the regulation of the actin-myosin cytoskeleton. This was further confirmed by the decreased velocity and the number of NMY-2::GFP foci in CAP depleted embryos. Furthermore, these embryos show mild decrease in PAR-2 domain size during the polarity establishment phase. cap-2(RNAi) embryos also show a delay in cell cycle progression, however the role of the cell cycle delay in the regulation of cortical contractions has to be determined. The characterization of CAP proteins, which are cytoskeleton-remodeling regulators, will improve our understanding of the mechanisms underling the establishment and maintenance of cell polarity, and thereby asymmetric cell division.

Keyphrases: C. elegans, PAR- 5, polarization, actin-capping protein
Une analyse du processus de justice transitionnelle au Pérou à la lumière du Droit international

The international human rights law has established obligations on States concerning how they must deal with the challenges inherent to transitioning societies: searching for the truth related to past crimes, persecuting and sanctioning those responsible of these crimes, and providing redress to the victims. Transitional justice has many political, social, and legal limitations that pose a challenge for States as well as for the international community at large. The objective of this research is to analyze – according to international law's parameters – the transitional justice's process that took place in Peru after the internal armed conflict and Alberto Fujimori's authoritarian regime. This study concludes that Peru has implemented international law's obligations while applying an integral approach to transitional justice. Nevertheless, there are still challenges linked to Peruvian society's political and social dimensions.

Keyphrases: Peru, Transitional Justice, International law, armed conflict, Alberto Fujimori, Violations of human rights, Inter-American Court of Human Rights, Impunity, Amnisties
La régulation de l’économie numérique au Sénégal : la convergence des télécommunications et de l’audiovisuel

Establish a regulation of the digital economy in Senegal represents a fundamental challenge for governments and all the players. In a more globalized approach, huge changes to normative rationalities and mechanisms of regulation, that have evolved over time giving a more important place to the right policies of states. Different regulatory and institutional models are well suited to support the phenomenon of convergence depending on the country's regulatory environment.  Regarding the current context of Senegal, the model of regulations relating to telecommunications and audiovisual, now converging, are based on a sectorial regulatory model. However, convergence has led to a blurring of boundaries which could pose enormous consequences normatively as the risk of confusion on the institutional or regulatory level. But nationally, there is to date no policy to sit the foundations of a convergent regulation.  There for, the question of whether sector regulation is relevant to the digital environment characterized by convergence. It turned out that it could be adopted as a short term model. But in order to achieve economies of scale to effectively regulate the different infrastructures and sectors requires a single regulatory model marked by the merger of ARTP and CNRA. Maintaining sector regulation will allow currying the transition to digital that already started and also the multispectral regulatory convergence will established converging markets.

Keyphrases: ARTP, CNRA, Convergence, Analogy, Digital
Travailleuses sociales diplômées à l’étranger : les enjeux du transfert de leurs connaissances au contexte de pratique montréalais

Abstract Social workers are part of a growing group of health and social services professionals who choose to immigrate to Quebec to live and pursue their careers. The recognition of diplomas obtained abroad and obtaining a license to practice issued by the Ordre des travailleurs sociaux et des thérapeutes conjugaux et familiaux du Québec are required in order to practice social work in Quebec. Once these milestones are met, the immigrant social workers begin their practice in a new professional and cultural universe, using the knowledge they acquired in their country of origin. From data obtained in the framework of a pan-Canadian qualitative research on the experience of immigrant social workers regarding their occupational adaptation (Pullen Sansfaçon, Brown and Graham, SSHRC 2011-2012, SSHRC 2012-2015), this master's thesis (by articles) explores the challenges inherent in the transfer of knowledge, professional experience and values obtained abroad, within a Quebec work context. The experience of 26 immigrant social workers, who graduated abroad and are currently working in the greater Montreal area, has been investigated, and has revealed both more and less transferable aspects of social work. The mission and values of social work, professional experience, theoretical knowledge and clinical skills have expanded beyond national borders. On the other hand, the discourse of participants indicates that the knowledge of laws, social policies, organizational procedures and language are transferred less easily, which can create gaps in a novel work setting relative to where the original social work training was obtained. In this context, the training and support of management, as well as the support of co-workers are both central to promoting the acquisition of local knowledge. Keywords : social work, immigration, professional, knowledge transfer, professional adaptation, Quebec

Keyphrases: immigration, Social work, professional, knowledge transfer, professional adaptation
Génération souverainiste? L'engagement des jeunes au sein du mouvement souverainiste québécois : le cas du Parti québécois

Since the defeat of the Yes campaign in the 1995 referendum, the Quebec sovereignty movement has been in decline. We can demonstrate this by analyzing the electoral results of the different sovereignist parties as well as the social and ideological division of the sovereignty movement over the past 20 years. This thesis seeks to analyse the involvement of Parti québécois (PQ) members between the ages of 20 and 26. These members began their involvement while the movement was already in decline and therefore have not lived through the most significant events of the Quebec sovereignty movement. With 16 semi-structured interviews, this study seeks to understand the political commitment processes of these individuals. Through a sociological analysis of their experiences of involvement in politics, we demonstrate that different types of processes can lead a person to join the PQ. We then argue that elements from the past, such as history classes and family socialization, have greater influence on a person’s awareness of the sovereignty issue than do current events. We proceed to establish that these individuals belong to a political generation for which the major events of the sovereignty movement cannot be considered as critical junctures in their political involvement. Finally, we demonstrate that the analysis of the individuals’ political orientations can help us better understand the differences between the different political commitment processes.

Keyphrases: Parti québécois, Political commitment, Quebec sovereignty movement, Parti québécois, Social movements, Quebec politics
Variations développementales chez les poissons hybrides clonaux Chrosomus eos-neogaeus : transgressions phénotypiques en 3D

An organism’s success is highly dependent on its phenotype. A major component of the phenotype is functional morphology because of its role in determining performance in a given environment clues as to their ecology. Morphological disparity and developmental differences between species can thus lead to ecological differences. This project assesses the role that mechanisms capable of generating morphological variation have in producing ecological differences between species within the hybrid fishes of the Chrosomus eos-neogaeus complex. Using X-ray based computer-aided micro-tomography and 3D geometric morphometrics, the shape of bones composing the jaws was described to measure morphological variation and developmental differences in the C. eos-neogaeus complex.  Chrosomus eos-neogaeus hybrids displayed as much variation as parental species and novel, deemed transgressive, phenotypes. Hybrids were also markedly different from parental species in their patterns of allometric scaling and phenotypic integration. Finally, hybrids appeared to be plastic and able to acclimate to different environments. The results of this study indicate that changes in the development of hybrids could lead to phenotypic and, in turn, ecological differences with parental species.

Keyphrases: Geometric morphometrics, µCT-scan, phenotypic transgression, hybridization, allometry, phenotypic integration, Chrosomus eos-neogaeus, hybridation
L’influence des capacités cognitives mâles et femelles sur le choix de partenaire chez le diamant mandarin (Taeniopygia guttata)

Successful foraging is essential for survival and reproductive success. When animals face rapidly change due to climate change or anthropogenic habitat destruction, they are force to quickly adjust their behaviour such as foraging. Innovation and learning, two processes related to cognitive functions, are know to allow animals to incorporate novel behaviours into their behavioural repertoires and thus to facilitate optimal responses to environmental change. Cognitive performance vary between and within individuals and although several studies have rencently addressed the causes, convicing evidences for why inter-individual variations in cognitive performance are maintained in a population are still lacking. During my Masters, I investigated different selective pressures acting on foraging performance on a novel motor task to better understand the evolution of cognitive abilities in a captive population of zebra finch (Taeniopygia guttata). Firstly, we investigated whether female zebra finches modify their mating preferences after having observed the foraging performance of males on a novel motor task. We also assessed each bird’s learning performance in a color associative task in order to check whether females could discriminate between the two males based on their learning performance. Discriminating among mates based on their cognitive ability might be very costly for females, especially in terms of time. Therefore, one way to reduce the cost of assessing mate would be to generalize their preferences to any male with the same phenotype as the most efficient observed individual. We finaly investigated whether female zebra finches can generalize their mating preferences after having observed a male’s foraging performance on a novel motor task. Our findings suggest that female zebra finches would be unable to assess male cognitive ability indirectly via morphological traits. However our results demonstrate that direct observation of the males’ performance on a foraging task can guide female mating preferences. We also demonstrates that female zebra finches can generalize the appearance of the male that is the most efficient at solving a motor task and then use this information to assessing new males. The relationship between cognitive performance and mating preference might be mediated throught habitat exploitation for example, but requires further investigation.

Keyphrases: Cognition, Problem-solving task, Learning, Innovation, Foraging performance, Mating preference, Natural selection, Sexual selection, Problem-solving performance, Associative learning, Zebra finch, Generalization