NCube/papyrus huggingface dataset:
Plasticité cérébrale dans le système olfactif : étude du modèle des sommeliers

This thesis is about the brain’s ability to adapt to an ever-changing environment. More specifically, it is about brain plasticity in the olfactory system. We used sommeliers, who are experts in olfaction, as our model. A first study allowed us to instate a protocol to assess sommeliers’ olfactory function. In a second study, we tested sommelier students at the start of their year-and-a-half-long training which is the prerequisite to become a professional sommelier. We observed that these future experts in olfaction already had, during the first two months of training, superior olfactory abilities. In a third study, we tested sommelier students again at the end of their training to examine the effects of a long-term olfactory training on olfactory performance and on the brain: beside assessing olfactory performance with the Sniffin’ Sticks test, we used magnetic resonance imaging (MRI) to examine the evolution of brain structure and function during sommelier training. Changes in brain structure constituted our main results. Firstly, olfactory bulb volume increased during sommelier training, which is in line with previous reports about this structure. Secondly, we observed a cortical thickness increase in the entorhinal cortex but also cortical thinning in other brain areas. Put together with findings from previous studies, these results support the recent overproduction-pruning model of plasticity according to which changes due to training-related brain plasticity are nonlinear but involve different processes and different phases. This model constitutes a great advance in the understanding of brain plasticity and its underlying mechanisms and should be considered in future studies about plasticity. Though neuroimaging results were interesting, results from olfactory tests in our longitudinal study were not conclusive so we conducted a fourth study to test the ability to identify odorants within mixtures, a task which is more complex and suitable for sommeliers than the Sniffin’ Sticks test. Sommeliers performed better. We also tested novices that we had trained on this task for five days to evaluate the effects of a short-term olfactory training.  This thesis is organized by articles. The first chapter is a general introduction, itself organized in several parts. These different parts define the major concepts of this thesis: olfaction, neuroanatomical correlations in the olfactory system, brain plasticity, plasticity in the olfactory system, neuroimaging. The last part concludes the introduction with aims and hypotheses. The following chapters are articles written during PhD that present the results of our research. The last chapter is a general discussion of all the results. Finally, two articles published during PhD, a chapter that is to be published in a book and unpublished results are presented as appendices.

Keyphrases: Olfaction, Sommelier, Brain plasticity, Neuroimaging, Brain, Training, Olfactory bulb, Cortical thickness, MRI
A novel purification method for binder of SPerm proteins and characterization of the protein interaction network of BSPH1

Binder of SPerm (BSP) proteins belong to a superfamily of proteins expressed in the male reproductive tract, particularly in seminal vesicles of ungulates (e.g., bovine, ram) and in the epididymis of humans and mice. So far, BSP proteins have been shown to play different roles in different species such as in motility and capacitation in bovine; however, their role remains unclear in other mammals. For instance, depletion of Bsph1/Bsph2 in mice had no effect on fertility. In order to elucidate the specific role of BSP protein in humans (BSPH1), I sought to investigate a purification method to produce functional human BSP protein, as these proteins are only present in minute amounts in the human epididymis. Following purification of BSPH1, I carried out in vitro experiments and sought to identify its protein interaction network. BSP proteins have been shown to interact with pseudo-choline groups such as diethylaminomethyl through affinity rather than ionic interactions. Diethylaminoethyl is positively charged and therefore is a weak anion exchanger, but BSPs interact through affinity to this resin. This study presents a new, rapid and cost-effective purification method that provides recombinant BSP proteins of a high purity level, which can be used to study their roles in mammalian fertilization. We showed that pre-incubation of oocytes with recombinant BSPH1 can decrease fertilization rate in a dose-dependant manner. Sperm were also preincubated with anti-BSPH1 antibody and showed a decrease in fertilization rate. Secondly, I used BioID (proximity-dependent biotin identification), coupled with mass spectrometry to identify the protein-protein interaction network of BSPH1 by proximity labeling. Mass spectrometry results showed an interaction between BSPH1 and all subunits of the CCT/TRIC complex (Chaperonin containing tailless complex polypeptide 1 (CCT) or tailless complex polypeptide 1 ring complex (TRiC). This complex interacts with another complex called BBSome (Bardet–Biedl syndrome complex), which plays a role in protein trafficking through primary cilium. I also identified BBS proteins, as well as other proteins, that interact with the BBSome complex and regulate protein trafficking in the cilia.  BSPH1 also interacted with a large number of CEP (centrosome-associated proteins) family proteins, important in the formation of primary cilium through microtubules and centrosome maturation, which further support the potential implication of BSPH1 with the primary cilia. Overall, this study demonstrates that BSPH1 may have a new role as a chaperone involved in protein trafficking through the primary cilia in cells that express it in the male reproductive system

Keyphrases: Male infertility, Protein purification, Affinity chromatography, Binder of sperm protein, Epididymal proteins, Proximity-dependent biotin Identification
Caractérisation moléculaire du syndrome CAID : mise en évidence des rôles non canoniques de SGO1 dans la régulation de la signalisation TGF-β et de l'épigénomique.

Rhythmic contractions are driven by the pacemaker activity of the cardiac sinus node and the intestinal interstitial cells of Cajal (ICC). We have discovered a new syndrome resulting from a combination of sick sinus syndrome (SSS) and chronic intestinal pseudo-obstruction (CIPO). This syndrome, which we have named Chronic Atrial and Intestinal Dysrhythmia (CAID), results from a recessive mutation in the SGO1 gene (K23E). However, the known roles of SGO1 do not explain the postnatal onset of the syndrome nor the specific pathology, suggesting that non-canonical roles of SGO1 lead to the clinical manifestations observed. This hypothesis is supported by the comparison of CAID with other cohesinopathies which mainly exhibit developmental phenotypes without or with mild cell cycle defects. This project aimed towards an unbiased discovery of noncanonical mechanisms explaining CAID using the molecular biology dogma (DNA→mRNA→protein) as a guideline.  We performed multi-omic screens on skin fibroblasts from CAID patients and healthy controls. Screening results were validated by electrophysiology, study of relevant signaling pathways, immunohistochemistry, LINE-1 retrotransposon pyrosequencing, and histone marks quantification. Our multiomics analyses confirmed changes in cell cycle regulation, but also in cardiac conduction and smooth muscle function. More specifically, several potassium channels were downregulated. Electrophysiology studies confirmed a decrease in the inward rectifier potassium current (IK1). Immunohistochemistry in CAID patient’s intestinal sections confirmed overexpression of SGO1 and BUB1, a regulator of TGF-β signaling pathway. Additionally, the canonical TGF-β signaling was increased and decoupled from noncanonical signaling. At the epigenetic level, CAID patient fibroblasts have a unique signature of hypermethylation and chromatin closure. This is supported by the increased methylation of H3K9me3 and H3K27me3. In conclusion, CAID syndrome is associated with several changes that, may have a cumulative effect rather than a single deregulated signaling pathway. Our results reveal the disturbance of the IK1 current, the deregulation of TGF-β signaling, DNA hypermethylation and chromatin accessibility changes as potential conductors of intestinal and cardiac manifestations of CAID syndrome. In particular, the TGF-β pathway and epigenetic changes, may be targeted by existing drugs, thus constituting promising therapeutic targets for the treatment of CAID syndrome.

Keyphrases: CAID syndrome, Sick Sinus Syndrome, Chronic and Intestinal Pseudo-Obstruction, SGO1, Cohesinopathy, TGF-β signaling, Epigenetics, Transcriptomics, Proteomics, Electrophysiology, Interstitial cells of Cajal, noeud sinusal, sinus node, Histology
Genome-wide CRISPR screens for the interrogation of genome integrity maintenance networks

The genetic material (DNA) of an organism contains the necessary information for survival, growth and reproduction. Loss of this information strongly impacts the health of the organism and is the leading factor in aging and cancer. Almost all cells in an organism contain a copy of said genetic material (genome) and employ several mechanisms to repair any damaged section of the genome and to accurately copy it during cell division. We sought to understand the cellular processes by which cells maintain genome stability by systematically inactivating individual genes to uncover their role using pooled CRISPR-Cas9 screening. We employed genome-wide CRISPR screening in human cell lines in combination with specific chemical perturbations to identify gene deletions that enhance or suppress the phenotype of the chemical treatment, thereby shedding light on the effect of the treatment or the role of said enhancer/suppressor genes. We first focused on resveratrol; a small molecule first discovered in plants that has been suggested to extend lifespan in model organisms while also inhibiting cell proliferation ex vivo. Chemical-genetic screening pinpointed a role of resveratrol in inhibition of DNA replication. When we compared the cellular effects of resveratrol to hydroxyurea, a known inducer of replicative stress, we found that both treatments led to slower replication fork progression and activation of signaling in response to replicative stress. Importantly, we showed that the inhibition of DNA replication by resveratrol in human cells is a primary effect on cell proliferation and independent of the histone deacetylase Sirtuin-1, which has been implicated as the primary target in lifespan extension by resveratrol. We then studied the perturbation of a second cellular process, namely telomere maintenance. These specialized sequences at the termini of chromosomes are critical for the protection of chromosome ends and their erosion is counteracted by the enzymatic activity of telomerase. We performed a genome-wide CRISPR screen in cells that were concomitantly treated with a specific telomerase inhibitor, BIBR1532. We uncovered a strong genetic interaction between telomerase and a previously unannotated gene, C16orf72, which we named TAPR1. We found that TAPR1-depleted cells led to elevated p53 levels, a transcription factor central for the cellular response to telomeric and global DNA damage. We propose that TAPR1 is a negative regulator of p53 protein levels by promoting its turnover. Altogether, these studies highlight the power of CRISPR-Cas9 in genetic screening to uncover novel insight into the human genome stability maintenance network.

Keyphrases: CRISPR-Cas9, telomères, inhibition de la télomérase, C16orf72, p53, genome-wide screen, DNA replication, telomeres, telomerase inhibition, replicative stress, resveratrol, cell proliferation
La socialisation des émotions chez les enfants en milieu scolaire et 
les différences de genre

Emotional competence is a factor that has the potential to greatly impact our well-being. Emotional competence can affect many aspects of his or her life, such as his/her professional career or even the quality of his/her relationships. The scientific literature showcases the existence of a link between the repression of emotions and mental health’s issues, behavioral disorders, bad academic performance and substance abuse (Ashiabi 2000; Chaplin, Cole, & Zahn-Waxler, 2005; Denham, Bassett, & Wyatt, 2007; Denham, Bassett, & Zinsser, 2012; Perlman, Camras, & Pelphrey, 2007). The development of emotional competence is a process that begins within the family circle and continues at school, with the help of teachers and educators. Because of the informal nature of the mechanisms at work, there are only a few studies on this very process. Furthermore, the few studies that examine the development of emotional competence by socialization in school tend to ignore the impact of gender stereotypes carried by teachers and other personnel. This paper is aimed to analyze grade school teachers’ behavior when they interact with their students in order to determine if said behaviors are influenced by students’ gender. This general goal was achieved by the completion of two sub-objectives. The first of these sub-objectives consisted in observing and analyzing the interactions between teachers and students in a sequential manner. The second was to explore the teachers’ belief system in regard to the emotional development of children and gender differences. Eisenberg, Spinrad and Cumberland (1998) introduced a heuristic model of emotional socialization that includes a number of variables such as parents’ personal beliefs and culture, and children’s characteristics (age, temperament, etc.) These authors suggest that emotional socialization is the factor of three processes: (1) parental reactions to children’s emotions, (2) socializers’ (teachers and other school’s personnel) discussion of emotion, and (3) socializers’ expression of emotions. A number of critics of this rich and complex model have been formulated, and we’ll address them in this paper. Denham et al. (2012) introduced a simpler model that doesn’t consider certain variables such as parents’ characteristics and instead put a greater emphasis on the aforementioned three dimensions of emotional socialization. In this study, we used the adapted model of Denham et al. (2012) was adopted. We recorded 3 different classes for 6 hours each and conducted semi-directed interviews with each class teacher. Our results suggest the existence of a gender difference related to emotional socialization. Teachers’ responses were significantly more negative towards boys’ expression of emotions compared to girls’. Results also point out the presence of gender stereotypes among teachers, which could influence their socialization practice and thus the level of emotional competence of their students.

Keyphrases: Socialization practice among teachers, Emotional socialization in kindergarten, Emotion repression, Gender differences
Quels motifs amènent des professeurs d'université à mettre en place des pratiques pédagogiques non magistrales dans le contexte de l'enseignement à de grands groupes?

The higher education, in specific the massification and reduction of the education budget, has created a context where teaching large groups of students has become a necessity, creating a challenge for university professors. Does the size of groups influence student success? Several studies, including those of Atkinson (2010); Milesi & Gamoran (2006) and Wulff et al. (1987), show that, in this teaching format, it is not the number of participants that matters, but the quality of teaching. In particular, Mulryan-Kyne's (2010) research points out that class size would not negatively influence learning if the teacher adopts teaching strategies adapted to the appropriate context. Faced with an increasingly heterogeneous audience and in the digital era, professors are making efforts to implement non-traditional practices geared towards student success and perseverance. As a result, this research aims to answer the following questions: What motivates university professors to implement non-lecturing pedagogical practices in the context of teaching large groups? And to the five specific questions: (1) What types of teaching have university professors experienced as students? (2) What reasons do university professors give for changing their teaching practices with large groups? (3) How have university professors experienced these changes in their teaching practices? (4) How are changes in teaching practices implemented by university professors? (5) How do university professors define large student groups? A qualitative study with semi-directed interviews was conducted with 21 professors from two universities in Quebec. Through thematic analysis and using paper support and QDA Miner software, our analysis highlighted, on the one hand, the process that seems to characterize the change in pedagogical practices among the professors we interviewed and, on the other hand, the main motivations that encouraged professors to engage in this change.

Keyphrases: University pedagogy, Non-traditional practices, Change process, Larges groups, Higher education
Représentation de l’agentivité historique dans des jeux vidéos : étude de cas multiples

The place of video games in popular culture is well established. Consumed by an increasingly large audience, they are interested in a variety of subjects, notably the past. Among the discourses of popular history, video games are arguably the newest. However, they are of increasing interest to educators and didacticians who wonder about their effects on pupils and their integration into humanities and social science courses. However, available research on historical video games are not numerous and only tell us about certain games (Assassin’s Creed, Sid Meier’s Civilization). In addition, they almost completely avoid the question of historical agency, even as video games set themselves apart from other popular representations of history by fostering interaction with the historical narrative they present. Our research therefore attempts to shed a new light on the matter by designing a typology of the representation of agency within historical video games, from a didactic perspective.  To do this end, we have developed an exploratory and qualitative methodology that uses a multiple case study. Our corpus is made up of five games, drawn from different video game archetypes : Assassin’s Creed: Black Flag, Battlefield 1, Company of Heroes, Medieval 2: Total War and Papers Please. We recorded nearly 56 hours of video clips, unevenly distributed between the cases in our study. The excerpts were analyzed as part of a thematic mixed-coded content analysis.  The results of our research show, among other things, that the representation of agency is directly linked to the nature and the type in which the game falls and that the historical narratives staged adopt a traditional view of historical agency. In addition, the factors of historical change are linked to the constraints imposed by video games as technical objects.

Keyphrases: Historical videogame, Agency, Historical change, History teaching, Historical thinking, Popular history
Pour un modèle d’éducation à la citoyenneté émancipatrice : les six vertus démocratiques du citoyen de liberté sociale

The theoretical and speculative research that is the subject of this thesis proposes a model of citizenship education that would have emancipatory aims. Following the tradition of critical sciences and Freire's critical pedagogy (1968), it first defends the idea that despite the ideological or political charge associated with it, citizenship education, like any form of formal or informal education, should pursue freedom and autonomy as its goals.  By taking as a basis the recent theses of the philosopher Axel Honneth (2015 and 2017), attached to the Frankfurt School, on the concept of social freedom and by exploiting the tools of the hermeneutics defended by Ricœur in particular, it was possible, firstly, to pro-pose a model of citizenship of social freedom and, secondly, to define some of the characteristics of citizens of social freedom. Finally, this work allowed us to identify skills and aptitudes that citizenship education, which would have freedom and emancipation as its goals, should help to develop or maintain. Because of their scope, we call these skills democratic virtues. The six democratic virtues that should be the object of teaching or learning and that our work pro-poses are 1) critical autonomy; 2) the capacity to deliberate and decide collectively; 3) recog-nition; 4) solidarity; 5) creativity; and 6) the capacity for action.

Keyphrases: Citizenship education, Critical pedagogy, Democratic virtues, Emancipatory citizenship education, Emancipatory education, Freedom, Social freedom
Designing supplementary space in multi-family housing

Demographics and lifestyles have changed considerably in the past few decades. These changes are bound to influence the design of housing and they notably include a series of emerging needs: additional spatial needs due to additional activities brought to the traditional housing premises. Planning for those emerging needs is the main theme of this thesis. In a typical single-family detached house, the basement is available to accommodate the spatial requirements for these emerging needs. However, such a provision does not typically exist in multi-family housing.  This thesis proposes a specific additional space to accommodate these emerging needs: the supplementary space. Although such a space has not been explored in the literature, there are precedents for its application in multi-family floor planning. The objective of this study is to provide guidelines for the design and the integration of this supplementary space. It relies on the systems approach as the design-decision methodology due to its logic of deducting the solution from the analysis of the objective. Applying the systems approach means that all the criteria corresponding to the specific purpose of the supplementary space will be extrapolated from the objective. However, once the supplementary space is being used to deal with emerging needs, it will then introduce its own relevant criteria. This study will start with the criteria for designing a home office because this is the most demanding emerging needs activity. The criteria are organized as vectors of a generic model indicating how the supplementary space can be formulated. The model will target the workplace at home and subsequently offer solutions to them. This study focuses on the planning provisions dealing mainly with visual and spatial privacy. The overall outcome of the model is to suggest guidelines to incorporate the supplementary space within multi-family residential buildings, a feature not offered in traditional planning.  The concept of adaptability is the key design strategy to accommodate change in architecture and housing, even more in the case of a supplementary space. Therefore, the supplementary space model will apply the concept of adaptability through the Open Building (OB) approach; elaborating more on the practical design and construction features. Different OB applications, such as the NEXT21 project and the KSI (Kikou Support and Infill) protocol in Japan, are examples that can be used as efficient guidelines to design a supplementary space.  The feasibility of the supplementary space model can be validated and served in the real world. Industrialized building systems are capable of accommodating change without demolition as their dry mechanical joints are generally at meeting the DfD (design for disassembly) standards, not only for the supplementary space but also for the whole dwelling unit.

Keyphrases: Socio-demographic changes, Emerging needs, Supplementary space, Systems approach, Workplace criteria, Knowledge model, Generic model, Housing types, Open building, DfD (design for disassembly)