NCube/papyrus huggingface dataset:
Étude des mécanismes moléculaires induits par Sonic hedgehog lors du guidage axonal des neurones commissuraux de la moelle épinière

Sonic hedgehog (Shh) is required for axon guidance of commissural neurons during spinal cord development, which involves reorganization of the actin cytoskeleton. Even if it is known that this process is regulated by small Rho GTPases, an effect of Shh on these proteins has not been clearly demonstrated. In this study, we show that Shh activates the small GTPases Rac1 and Cdc42. This activation occurs rapidly, which is compatible with the guidance effects of Shh on commissural neurons. In parallel, we characterized the Shh-dependent activation of Boc, which is a Shh receptor required for commissural axon guidance. Taken together, these results help refine our understanding of the signal transduction mediated by Shh during axon guidance of commissural neurons.

Keyphrases: Rac1, Cdc42, GTPase(s), Boc, Smoothened, Shh
Lactobacillus helveticus R0052 et Bifidobacterium longum R0175 en combinaison réduisent l’apoptose dans le système limbique après ischémie myocardique transitoire chez le rat

Apoptosis is observed in limbic system after a myocardial infarction (MI). This cell death is due to the release of pro-inflammatory cytokines. Since probiotics reduce the pro/anti-inflammatory cytokine ratio, we hypothesise that probiotics will lessen apoptosis in the limbic system following MI. Methods: Rats were given probiotics or placebo for 4 consecutive weeks. Rat in the probiotic group received a daily dose of over 1 billion live bacterial cells of Lactobacillus helveticus R0052 and Bifidobacterium longum R0175 in combination. A MI was then induced in anesthetised rats by a 40-minute occlusion of the left anterior coronary artery followed by a 72 hours of reperfusion. Infarct size was measured and apoptosis was determined in the amygdala and hippocampus in both groups. Results: Infarct size was not diminished in the probiotic group (45% of the risk area), apoptosis was lessened in the dentate gyrus (DG), the lateral (LA) and medial (MA)amygdala compared to the placebo group. Caspase-3 and Bax/Bcl2 ratio were reduced in the probiotic group by about 50% and 40% respectively. Akt activity was increased by 35% in these regions. No difference was observed in the hippocampus Ca1 and Ca3 regions. Conclusion: This probiotic combination can reduce the apoptosis found in specific regions of the limbic system following a MI, which may have significance for post-MI depression.

Keyphrases: Cytokines, Probiotics, Myocardial infarction, Myocardial reperfusion, Apoptosis, Cytokines, Limbic system
Mortalité adulte et longévité exceptionnelle au Québec ancien

This thesis presents, in the first part, a detailed study of adult mortality of French-Canadians born between 1620 and 1749. New time published results are presented in the form of abridged life tables with staggered entries. The life tables are compared to ascertain behavioural differences between men and women, between residents of urban and rural regions and across three generations during the period studied. In the second part, the thesis presents a case study conducted to test the influence of inheritance on human longevity. A family distinguished by the exceptional longevity of several of its members is compared to a reference fictional family representative of the average population of the time. Evidence provided on these two families consists of mean ages at death and proportions of survivors at different ages. This case study builds on research conducted with the ancestry of Jeanne Calment and Marie Louise Meilleur. Information drawn from the parish registers of old Quebec computerized by the Programme de recherche en démographie historique (PRDH) in a database called Registre de la population du Québec ancien (RPQA) is the primary source used for the life tables and case study.

Keyphrases: adult mortality, Québec ancien, former Quebec, life tables, longevity, inheritance, démographie historique, historical demography
Rôle des macrophages contre Candida albicans chez la souris transgénique exprimant le génome du VIH-1

Oropharyngeal candidiasis (OPC) is the most frequent opportunistic fungal infection among HIV-infected patients. Despite the profound immunosuppression caused by HIV-1, Candida albicans infection is limited to the oral epithelium and rarely disseminates to deep organs. The CD4C/HIVMut transgenic (Tg) mice, which expresses the truncated HIV-1 genome, developed a chronic OPC after oral inoculation with C. albicans that closely reproduces infection in seropositive patients. Here, we used this Tg mouse to investigate the contribution of macrophages in limiting candidiasis to the oral mucosa. This study shows that i) macrophages are recruited to the oral and gastric mucosa in response to C. albicans despite transgene expression, ii) the macrophages of this Tg mouse exhibited a polarization toward an alternatively activated phenotype and iii) nitric oxide production by these macrophages is dispensable for limiting chronic oral carriage and for preventing systemic dissemination of the fungi in these Tg mice. Overall, these result indicate that macrophage do not directly determine the susceptibility to chronic carriage of Candida in these CD4C/HIVMut Tg mice.

Keyphrases: Oropharyngeal candidiasis, Macrophages, Macrophages, HIV-1, Mouse model
L'étude du rôle immunomodulateur des IVIG dans un modèle murin humanisé de réaction du greffon contre l'hôte

Graft-versus-host disease (GvHD) is a major complication following hematopoietic stem cell transplantation (HSCT), occuring in 30 to 70% of HSCT despite proper prophylactic treatment, and can result in death. It is therefore primordial to improve the prophylactic treatments in order to reduce the frequency and severity of GvHD. Since these prophylactic treatments are based on the use of immunosuppressive agents, they inhibit the immune reconstitution and thus increase the risk of infections and relapse. Because of their immunomodulating properties, immunoglobulins (IVIG) represent a promissing alternative. Furthermore, IVIG are already widely used in patients with immune deficits. Since no study has yet clearly shown that IVIG can reduce GvHD without inhibiting the immune reconstitution in the patient, the scientific community is still debating their usefullness in GvHD prevention. Should their efficacy to reduce the incidence and severity of GvHD without impairment to the immune reconstitution be demonstrated, the use of IVIG could change the clinical outcome for HSCT patients, improving their remission and quality of life. The objectives of this project are to evaluate IVIG efficacy in GvHD prevention and to define the mechanism of action of IVIG. To fulfill these objectives, we will use a GvHD humanized mouse model, which consists of injecting huPBMCs in immunodeficient mice who can not reject them. Our results demonstrate an immunomodulatory effect of IVIG, allowing for reduced clinical signs and a slighlty increased survival in GvHD. A population of NK cells also appeared upon IVIG treatment and is believed to be indirectly induced by IVIG.

Keyphrases: Gvhd, Ivig, Hsct, Gvhd, Humanized mice, Ivig, Hsct, Immune reconstitution, Nk cells
Les formes de l'illégitimité intellectuelle: genre et sciences sociales françaises entre 1890 et 1940

In this dissertation in historical sociology, I analyze gender relations and the construction of women’s intellectual legitimacy in the French social sciences between 1890 and 1940. To that end, I study the social positions, the intellectual productions, and the reception of women in the main social science periodicals leaning towards sociology and anthropology. The pivotal point of my demonstration is women’s university enrolment and graduation. The first part of my dissertation is about women lacking a university diploma that nevertheless played a role in the social sciences before 1914, mainly through participating in the reformist circle of influence or by being involved in feminine and feminist groups. The “legitimate feminine figures”, i.e. women whose works did not fuel any kind of controversy, are in the most heteronomous parts of the field of study, in which issues about the reformist practice prevail over issues about knowledge. On the other hand, the “figures of transgression”, i.e. women lacking a diploma but pretending to participate in social empirical and theoretical knowledge, provoke negative reactions that, in turn, relegate their heterodox feminist analyzes to the political field. After 1914 and until 1940, the amount of women and of feminine works in periodicals and French social science groups decreased, and women with a university diploma replaced those lacking one. The gender-differentiated processes of evaluation, which contributed to reformulate the antinomy between intellectual competence and femininity, adapted itself to the fact that women had access to university diploma. On the one hand, the majority of newly graduated women heads and is directed towards new social professions (mainly social work) and teaching. Both professions promote competences traditionally associated with women, and construct the latter’s professional identities as disjoint from intellectual, and mainly theoretical, activities. On the other hand, the only graduated women aspiring to stay within the field of the social sciences, and who succeeded before 1940 in gaining a relative recognition for their competence, pursued empirical research, accomplished their work in accredited institutions, took on problems and perspectives sanctioned by the expert community, and did not play the role of feminist activists.

Keyphrases: France, gender, social sciences, sociology, anthropology, intellectual legitimacy, feminism, France, naturalism, differentialism, education
Étude de l’étoile Wolf-Rayet variable WR 46 dans l’ultraviolet lointain et les rayons X

The Wolf-Rayet star WR 46 is known to exhibit a very complex variability pattern on relatively short timescales of a few hours and also on longer timescales of months. Periodic but intermittent radial velocity shifts of optical lines as well as multiple photometric periods have been found in the past. Nonradial pulsations, rapid rotational modulation or the presence of a yet-to-be-confirmed low-mass companion have been proposed to explain the short-term behaviour. In an effort to unveil its true nature, we observed WR 46 with FUSE over several short-term variability cycles. We found significant variations on a timescale of about 7.5 hours in the FUV continuum, in the blue edge of the absorption trough of the O vi 1032, 1038 doublet P Cygni profile, and in the S vi 933, 944 P Cygni absorption profile. We also retrieved archival XMM-Newton data of this star. We found the X-ray light-curve to show variations on a timescale similar to the UV and FUV continuum light-curves, and the X-ray spectrum of WR 46 to be very soft with a peak below 1 keV. We discuss the different constraints on the nature of the variability that these new observations help to establish. Among the suggested scenarios, we conclude that non-radial pulsations is the most likely, although we are far from a complete picture.

Keyphrases: Wolf-Rayet, WR 46, Stars, Wolf-Rayet, WR 46, X-ray emission
L'habitude en matière de conduite automobile : une analyse de ses composantes et du rôle qu'elle joue dans le maintien et la régulation des comportements de conduite

“The vast majority of accidents remain related to the dangerous behaviors of road users”.  This straightforward statement is now accepted as a truism by the road safety community, although it is based on questionable premises.  The most basic problem is that the research done during last decades was almost completely focused on analyzing solely the failing aspects of driving – accidents, traffic offences, driving errors and mistakes, high-risk and dysfunctional drivers, attitudes and psychological traits that may lead to dangerous driving, etc.  In so doing, we came to forget that we still have plenty to learn about the art of ordinary driving.  How can we expect to address the entire process of road accidents without first having identified, and clearly understood, the mechanisms of “regular” driving?  How can we deepen our understanding of driving behaviors if we are completely ignoring all the usual, “normal” activities people do as they are driving their vehicles?  This thesis was realized with the view to better understanding the driving behaviors, taking into account their diversity and richness.  The study more specifically looked into the issue of habits, as they are a significant aspect of driving behaviors, but also as they are resilient, in that they pose real barriers to all those who are trying to change individual driving behaviors.  In-depth interviews with 30 drivers, male and female, aged between 17 and 54, were meant to answer the following questions, among others: What are the different driving habits made of?  To what extent do they direct driving behaviors?  How do they hamper the change or modification of adopted practices?  What are the factors that lead them to set in?  The results of the analysis laid the foundations of a driving behaviors model in which body sensations take a central role, and the habit – which is more related to the idea of comfort than to ideas of automatism or repetition – contributes not only to the sustainability, but also to the regulation of the various behaviors adopted on the roads.

Keyphrases: Sensation, Driving behaviors, Habit, Sensation, Comfort, Emotions, Traffic safety, Usual driving
Étude du rôle de la MAP Kinase non-conventionnelle ERK3 dans le développement thymique et l'activation des lymphocytes T

Classical MAP kinases (MAPK) play essential roles during T cell development and activation. ERK3 is a member of the MAPK family for which no physiological function has been described yet. Also, ERK3 is an atypical MAPK since its structure and mode of regulation are different from the conventional MAPK. Even today, the events leading to ERK3 activation and its substrates or partners are still largely unknown. We have studied in this thesis the role of ERK3 during T cell development and activation by using a mouse model in which ERK3 is not expressed. First, we have established that ERK3 is expressed in thymocytes. Next, we have evaluated thymic development in ERK3-deficient mice and we have observed a significant decrease in cell number at DN1, DP and CD4SP stages of T cell development. ERK3-deficient hematopoietic chimeras revealed that the DN1 and DP phenotype are T-cell autonomous, while abrogation of CD4SP development requires ERK3-deficiency in both thymocytes and thymic epithelium. By investigating further the DP stage, we have shown that ERK3-deficient DP thymocytes are more prone to apoptosis and also accumulate DNA double-strand breaks (DSBs). Moreover, we have shown that the increase DSBs are the direct consequence of RAG activity and that abolition of RAG almost restored thymic cellularity in ERK3-deficient mice. These results suggest that ERK3 is involved in an essential mechanism of DBSs regulation during TCR recombination. In the second article presented in this thesis, we have shown that ERK3 is expressed in peripheral T cell, but only when their TCR is activated. Also, ERK3-deficient T cells presented a strong reduction in proliferation and cytokine secretion following in vitro stimulation. Moreover, activated T cells lacking ERK3 are not more prone to death and surprisingly, they are unable to up-regulate the expression of the anti-apoptotic molecule Bcl-2 following TCR stimulation. These results suggest that the reduced proliferation of ERK3-deficient T cells is a consequence of their defective activation.  Collectively, our results unveil essential and unsuspected roles for ERK3 in T cell development and activation. With this study, we establish for the first time an in vivo function for the atypical MAPK ERK3 in two different stages during T cell life.

Keyphrases: MAP Kinases, ERK3, Activation, T cell development, Differentiation, Proliferation, T cell activation
La notion de fonctionnalité en droit canadien : quels fondements pour quels usages?

This memory analyzes the notion of functionality. Of case law origin, this concept tends to maintain the traditional dichotomy between trademarks and patents regimes. In light of judgments rendered on that matter, the preservation of such dichotomy would notably prevent from illegally prolonging a monopoly fallen under the regime of patents by the registration of a trademark. This study tries to understand the concept of functionality and, more specifically, to justify its existence. In order to reach this goal, a detailed study of the regimes of trademarks and patents lead us to conclude that each of these bodies of rules answers to a different logic. Indeed, the functions of trademarks and patents are different and no overlapping seems to be allowed. This situation is particular to these two specific regimes. An examination of the area of the notion of functionality leads us to notice that other rights of intellectual property can coexist. For example, we believe that an intersection is possible between the regimes of industrial designs and trademarks. As a conclusion, we notice that the notion of functionality is a well established principle in Canada which tends to prevent any perpetual renewal of a patent under the trademarks regime. We believe that the existence of this concept is justified under trademarks and patents laws. However, this conclusion could differ within the framework of the other intellectual property rights, since these other rights' functions seem to allow an intersection between them.

Keyphrases: Invention, Counterfeit, Distinctive character, Distinguishing guise, Functionality, Invention, Monopoly, Patent, Registration, Trademark, Use
Le droit d'auteur sur la mise en scène

Stage directions are not c1early protected under the current wording of the Copyright Law. This is why we wonder which legal qualification would be most appropriate. Is the stage director a performer or an author? We study the possibilities of legal qualification for stage direction, according to its artistic characteristics by production types, and considering the different factors which influence the Stage Director's liberty as well. The possibilities are vast since the Stage Director works in collaboration with several other intervening parties. Also, the Stage Director meets two typical obstacles: fixation and originality. We conclude that the Stage Director is an author because each and every aspect of the stage directions are copyrightable, under different legal qualifications.

Keyphrases: Fixation, Copyright, Stage director, Theatre, Performer, Literary work, Dramatic work, Artistic work, Derivative work, Fixation, Originality
Facteurs influencing haptic shape perception

The purpose was to determine the contribution of several factors (design of the task, angle orientation, head position and gaze) to the ability of subjects to perceive differences in twodimensional (2-D) shape using haptic touch. Two series of experiments (n=12 each) were carried out. In all cases the angles were explored with the index finger of the outstretched arm. The first experiment showed that the mean threshold for 2-D angle discrimination was significantly higher, 7.4°, than for 2-D angle categorization, 3.9°. This result extended previous work, by showing that the difference is present in the same subjects tested under identical conditions (knowledge of results, visual test conditions, angle orientation). The results also showed that angle categorization did not vary as a function of the orientation of the angles in space (oblique, upright). Given that the angles presented were all distributed around 90°, and that this may be a special case as in vision, this finding needs to be extended to different ranges of angles. The higher threshold with angle discrimination likely reflects the increased cognitive demands of this task which required subjects to temporarily store a mental representation of the first angle scanned, and to compare this to the second scanned angle. The second experiment followed up on observations that categorization thresholds are modified with gaze direction but not head position when the unseen angles are explored in an eccentric position, 60° to the right of midline. This experiment tested the hypothesis that the increased threshold when gaze was directed to the far right might reflect an action of spatial attention. Subjects explored angles located to the right of midline, systematically varying the direction of gaze (away from or to the angles) along with angle location (30° and 60° to the right). Categorization thresholds showed no change across the conditions tested, although bias (point of subjective equality) was changed (shift to lower angle values). Since our testing with far right gaze (away) had no effect on threshold, we suggest that the key factor contributing to the increased threshold seen previously (head forward/gaze right) must have been this particular combination of head/gaze/angles used and not spatial attention.

Keyphrases: haptic perception, shape, gaze, head position, spatial location
La Visualisation in vivo des « espèces oxygénées radiculaires» au niveau des cellules ganglionnaires de la rétine

Title: Imaging Reactive Oxygen Species in RGCs In vivo Purpose: Reactive oxygen species not only are generated as a result of cellular injury, but also serve as signaling molecules for a variety of critical processes, including mitosis and cell death. We previously reported that injury to RGC axons induces a burst of superoxide within the cell body, probably of mitochondrial origin (Lieven et al, 2006). We now describe a method for imaging of reactive oxygen species within the retina of the living animal using a confocal scanning laser ophthalmoscope called the Heidelberg Retina Angiograph 2 (HRA2) equipped with dual lasers. Methods: Following preliminary studies using other indicators (hydroethidium; HEt) for reactive oxygen species, we attempted to image reactive oxygen species in the in vivo model using 5-(and-6)-chloromethyl-2',7'-dichlorodihydrofluorescein diacetate, acetyl ester (CM-H2DCFDA). The resultant images were quantified using ImageJ. One optic nerve of Long-Evans rats was crushed intraorbitally, sparing the retinal circulation. In some rats the superior colliculi of Long-Evans rats had been previously exposed via craniotomy and overlaid with Gelfoam saturated with indocyanine green (ICG). At varying time points the animals were injected intravenously or intravitreally with HEt or CM-H2DCFDA and imaged with fluorescein and/or ICG filters using the HRA2. Results: We demonstrated multiple bright foci of fluorescence in the ganglion cell layer when we retrogradely labeled with ICG bilaterally, indicating that ICG was a retrogradely transported dye that could be detected with the HRA2. Following axotomy and intravitreal injection of CM-H2DCFDA, there was bright fluorescence in the fluorescein channel in a few cells in the ganglion cell layer, consistent with production of one or more reactive oxygen species. There was no cross-talk between the fluorescein and ICG channels when detecting ICG or CM-H2DCFDA, respectively. Conclusions: Retrograde labeled RGCs can be identified and levels of reactive oxygen species measured using a dual frequency confocal scanning laser ophthalmoscope. Keywords RGCs, oxidative radical, imaging

Keyphrases: Retinal ganglion cells, Oxidative radicals, Imaging