NCube/papyrus huggingface dataset:
Découverte d'un gène causant une ataxie spastique héréditaire dominante dans la population de Terre-Neuve

Hereditary spastic ataxias comprise a family of heterogeneous disorders resembling both hereditary ataxias and hereditary spastic paraplegias. The similar symptoms are ataxia, which is a problem with limb coordination due to cerebellar damage, and lower-limb spasticity due to corticospinal tract degeneration. Only one spastic ataxia inherited in an autosomal dominant fashion has been reported in the literature: SPAX1. The locus was identified in 2002 using three families from Newfoundland with the specific phenotype. This thesis reports the discovery of the causative mutation in the VAMP1 gene, which encodes VAMP1/synaptobrevin 1, a synaptic protein involved in neurotransmitter exocytosis. Experiments characterizing the effect of the mutation on RNA were conducted, leading to a possible molecular explanation of the symptoms.

Keyphrases: VAMP1, ataxia, spastic paraplegia, genetics, founder effect, dominant inheritance, VAMP1, splicing
Habitudes de vie et contrôle glycémique chez des adultes atteints de diabète de type 1 : des barrières envers l’activité physique au calcul des glucides

Type 1 diabetes (T1D) is a complex disease requiring continuous self-management. Physical activity (PA) and carbohydrate counting are essential counterparts to insulin therapy for blood glucose control in order to prevent complications and comorbidities.  We have demonstrated the validity (predictive validity, internal validity and reproducibility) of the BAPAD-1 scale to assess perceived barriers associated with PA practice. Fear of hypoglycemia is the strongest perceived barrier among adults with T1D. An active lifestyle, as described by a physical activity level (ratio of total over resting energy expenditure) ≥ 1.7, is associated with a better body composition compared to less active adults. Adults who are more active show significantly less fat mass, smaller body mass index and smaller waist circumference.  Motion sensors, like the SenseWear Armband™, are useful to estimate PA level. To complement prior validation studies, we evaluated and confirmed the reproducibility of the SenseWear Armband™ measurements. However, we also observed that energy expenditure is underestimated at the onset of moderate intensity ergocycling. Thus, this motion sensor should be used to evaluate energy expenditure over long periods of time rather than short length exercise.  Carbohydrate counting is a widely used method to evaluate prandial insulin doses. We evaluated, in a real-life setting without prior method revision, the accuracy of adults with T1D for carbohydrate estimation. The mean meal error was 15.4 ± 7.8 g or 20.9 ± 9.7 % of total carbohydrate content. The mean meal error was positively associated with larger daily glucose fluctuations measured by a continuous glucose monitoring system. Regular educational tips regarding carbohydrate counting may be necessary to improve glycemic control.   In order to improve PA practice, we developed and tested in a randomized controlled trial a PA promotion program (PAP-1). This 12-week program includes a weekly group session designed for PA initiation, goal setting and improving knowledge about glycemic control during PA. Even if the program failed to improve total energy expenditure, participants improved their cardiorespiratory fitness and blood pressure. At the end of the program, a larger proportion of the participants were knowledgeable of insulin pharmacokinetics and they used more various methods to prevent hypoglycemia related to PA.   In conclusion, type 1 diabetes obtrudes many daily challenges. On one hand, carbohydrate counting is a complex job and its inaccuracy is associated with glycemic fluctuations. On the other hand, even if having an active lifestyle is associated with a better body composition, fear of hypoglycaemia may impede PA practice. The PAP-1 program offers support to adults with T1D to adopt an active lifestyle and thus improve some cardivascular risk factors.

Keyphrases: Type 1 diabetes, Physical activity, Barriers, Carbohydrates, Insulin therapy, Motion sensor, Body composition
Transmission des voies olfactives aux cellules réticulospinales de la lamproie

Olfactory inputs are known for their ability to induce specific motor behaviors. Despite numerous behavioral observations in vertebrates, the mechanisms and the neural pathways underlying the olfactory-locomotor transformation are still unknown. In lamprey, recent studies have described this pathway and the mechanism underlying the transformation of olfactory input into a locomotor activity (Derjean et al., 2010). This pathway originates in the medial part of the olfactory bulb, sends projections to the posterior tuberculum, a diencephalic region. From there, the neurons project directly to the mesencephalic locomotor region that is known to send projections to the reticulospinal neurons to activate locomotion.  Using lamprey brain preparation, electrophysiology and calcium imaging, the aim of this study was to establish whether all reticulospinal neurons respond to olfactory stimuli. Electrical stimulation of the olfactory nerves, the medial part of the olfactory bulb or the posterior tuberculum activates all reticulospinal cells in the four reticular nuclei (ARRN: Anterior rhombencephalic reticular nucleus; MRN: middle mesencephalic reticular nucleus; MRRN: middle rhombencephalic reticular nucleus; PRRN: posterior rhombencephalic reticular nucleus). The medial part of the olfactory bulb is the only region that is implicated in transmitting the olfactory information to reticulospinal neurons. We also discovered that when blocking the GABAergic receptors in the medial part of the olfactory bulb, the reticulospinal neurons have a stronger response to olfactory stimulation. Thus we showed that a tonic inhibition is involved in the modulating depression of the olfacto-locomotor pathway.  Altogether, this work shows that stimulation of the olfactory sensory inputs activates simultaneously the entire population of reticulospinal neurons that control locomotion. In addition, there is a GABAergic tonic inhibition at the level of the medial part of the olfactory bulb that causes a modulating depression in the olfacto-locomotor pathway.

Keyphrases: Olfactory-locomotor transformation, olfactory nerve, olfactory bulb, posterior tuberculum, mesencephalic locomotor region, reticulospinal neurons, tonic inhibition, lamprey, electrophysiology, calcium imaging
Un modèle global et intégré de la performance : application à l’urgence d’un hôpital au Mexique

Because of the complex, nonlinear nature of their operations, emergency rooms (ER) represent unique organizational entities in healthcare. ERs suffer from increased pressures as the result of current social and health care system dynamics, and thus face distinctive challenges like the crowding phenomenon. Contrary to the prevailing thought among researchers, the present work establishes that crowding is a manifestation of poor performance rather than one of operational failure. Therefore, organizational performance is of indisputable importance to emergency rooms. Indeed, the study of performance is a current subject among health services researchers. It is, however, a concept that has been historically difficult to define because of its complex, multidimensional and paradoxical nature.   The EGIPSS model, based on Parson’s Social Action Theory, is capable of seizing this complexity and constitutes a solid and comprehensive framework, capable of adapting to different contexts. This thesis adopts the EGIPSS model in order to present a global and integral tool for the evaluation of the organizational performance of the emergency room at Regional General Hospital 46 in Guadalajara, Mexico. This instrument is conceived to specifically address the particularities of ERs, as well as the unique organizational characteristics of Regional General Hospital 46 and the Mexican Health System. Thus, the development of this thesis project contributes to the continuous performance improvement efforts of this institution, and adds to the knowledge of emergency rooms as complex organizations.

Keyphrases: EGIPSS, IMSS, performance, crowding, EGIPSS, emergency room, emergency department, performance, Mexican Health System, IMSS, Mexico
Expression profile of plasticity-related mRNAs in the cortex and hippocampus of young and aged rats and of 3xTg and wild type mice

Recent work has demonstrated that dysregulations in the expression profile of plasticity-related genes in specific brain regions contribute to age-related cognitive decline and Alzheimer’s disease.  The aim of this study was to determine the expression profile of a subset of plasticity-related mRNAs in different regions of the brain of young and aged rats as well as 3xTg and wild type (WT) mice.   qRT-PCR experiments were performed in extracts of cortex and hippocampus of young and aged rats and of 3xTg and WT mice, respectively.  Results demonstrated significant increases in the expression of MAP1B, Stau2, CREB, BDNF, and AGO2 mRNAs, especially in the hippocampus (CA1-CA3 fields) of 3xTg mice compared to WT mice.  A significant decrease was also observed in the expression of αCaMKII mRNA in the cortex of 3xTg mice compared to WT mice.  On the other hand, no significant changes were observed in the expression of plasticity-related genes in the hippocampus of aged rats compared to young rats.   These results confirm that alterations in gene expression occur at the onset of AD and possibly contribute to the progression of the disease by causing an imbalance between long-term potentiation and long-term depression. In addition, patterns of significant altered gene expression, especially in the hippocampus (CA1-CA3 fields) of 3xTg mice are consistent with the progression of AD whereby the hippocampus (CA1 region) is most vulnerable at the onset of the disease.  These results provide a better understanding of the molecular events that first become disturbed in AD.

Keyphrases: Cortex, Synaptic plasticity, mRNAs, Cognitive decline, Alzheimer disease, Young rats, Aged rats, 3xTg mice, WT mice, Cortex, Hippocampus
A Teacher’s Formative Assessment Perceptions and Practices in Oral Intermediate English Courses at the Université de Montréal

During the last twenty years, assessment practices for improving student learning (i.e., self-assessment, peer assessment, feedback) in the classroom has been considered as essential (Black & Wiliam, 1998; Harlen & Winter, 2004; van de Watering & van der Rijt, 2006). In the field of second language learning, however, research in this area is quite limited. In order to address this gap, an exploratory research , based on Colby-Kelly and Turner’s (2007) and Lyster and Ranta’s (1997)studies has been conducted . The general objective was to understand how formative assessment is practiced in two Intermediate Oral English courses at the Université de Montréal and to compare how these practices are perceived and performed by the teacher and the students.  Three research questions were pursued:  1. What is the nature of formative assessment in a second language classroom setting? 2. Do the teacher’s assessment practices reflect what she thinks about formative assessment? 3. What are the coincidences and differences between teacher’s perceptions and her students’ perceptions regarding the benefits of formative assessment for learning English? Data collection instruments consist of teacher interview guidelines, students’ questionnaire and classroom observation grids. In order to answer the first question, the feedback given by the teacher during the students’ oral performance has bee analysed using the types of feedback and uptake in Lyster and Ranta’s (1997) report. For the second research question, I interviewed the teacher at the beginning of each session and I elicited her beliefs about classroom-based formative assessment practice. At the end of the session I the teacher’s answers have beeb compared and contrasted with her actual performance, which was videotaped during the course. Finally, regarding the third question, teacher’s answers in the interviews have been compared with students’ answers on a questionnaire – adapted from Colby-Kelly and Turner’s one.  The most significant results of this qualitative research are presented and discussed. In the conclusion, directions for future research are proposed

Keyphrases: Perceptions, Formative assessment, Summative assessment, Higher education, English as a second language
Modulation de la réponse immunitaire dans le cerveau par la barrière hémato-encéphalique : implication en sclérose en plaques

Multiple sclerosis (MS) is an immune-mediated disorder of the central nervous system (CNS) characterized by multifocal areas of leukocyte infiltration and demyelination associated with a breakdown of the blood-brain barrier (BBB). Typically, demyelination is centered around perivascular accumulation of CD4+ and CD8+ T lymphocytes, monocytes, macrophages and dendritic cells (DCs) that arise from migration of peripheral blood immune cells across the CNS microvascular endothelium.  We have thus suggested that the migration across the BBB of immune cells subsets from the blood is controlled by molecular mechanism specific for each cell type. To answer this hypothesize, we have performed four different studies. We first show a beneficial effect of statins on the BBB, restricting the migration of lymphocytes and monocytes as well as the diffusion of soluble molecular tracers. This phenomenon is mediated through abrogation of isoprenylation processes that is probably inhibiting the ability of endothelial cells of the BBB to contract. We also show that CD14+ monocytes migrate across the inflamed human blood BBB and differentiate into DCs in response to BBB-secreted TGF-beta and GM-CSF. These DCs then promote the proliferation and expansion of inflammatory CD4+ T lymphocytes. We demonstrate that the migration of monocytes is controlled by a new adhesion molecule called Ninjurin-1. Ninjurin-1 neutralization specifically abrogated the adhesion and migration of human monocytes across endothelial cells of the BBB, without affecting lymphocyte recruitment. Moreover, Ninjurin-1 blockade reduced clinical disease activity and histopathological indices of experimental allergic encephalomyelitis (EAE). Finally we show that migration of CD8+ T lymphocytes across BBB is dependent on alpha-4 integrin. Also, the majority of CD8+ T lymphocytes found in the cerebrospinal fluid of MS patients, and in the CNS of EAE mice as well as the CNS of mouse infected with hepatitis virus are showing an effector memory phenotype. These data could explain the numerous cases of progressive multifocal leukoencephalopathy seen in natalizumab treated MS patients. In conclusion, our study unveils an important role of peripheral monocytes in MS. The inhibition of migration of these cells to the CNS could be a beneficial therapy since it would allow immune surveillance of the brain. The statins could also be a very interesting option since these molecules would reduce the inflammatory processes involved in MS.

Keyphrases: Monocytes, Nerve injury-induced protein (Ninjurin)-1, Multiple sclerosis, Experimental allergic encephalomyelitis, Blood-brain barrier, Migration, Monocytes, Dendritic cells, T lymphocytes, Alpha-4 integrin, Statins, Nerve injury-induced protein (Ninjurin)-1
La protéine Nef du VIH-1 altère la fonction de Lck dans les thymocytes de souris transgéniques

HIV-1 Nef protein plays an essential role in the HIV-1 pathogenesis by modulating the host signaling transduction pathways. TcR signalling is important for the thymic selection process to CD4 and CD8 single positive T cells and is greatly dependent on the activity of Src kinase Lck and its ability to bind to CD4 and CD8 cytoplasmic tail. We previously found that expression of HIV or SIV Nef can induce severe thymocytes depletion and downregulation of CD4 expression in Nef+ mice. We also recently showed that Nef blocks generation of double positive thymocytes and impairs DP to CD4+ SP T cells transition. The reversal of this phenotype was accomplished by several approaches, among them by crossing Nef+ mice with mice expressing constitutively active Lck Y505F. These results imply that the maturation of CD4+ T cells is disrupted due to impairment of Lck-mediated CD4 receptor signaling. However, the molecular mechanisms by which Nef contributes to the impairment in thymic CD4 generation remains largely unclear.  In this study, using confocal microscopy and biochemical approaches, we found that Nef+ thymocytes express more Lck than the Nef- control. Despite of this increase, a significant portion of Lck molecules were unable to reach to the plasma membrane. It was significantly accumulated in the intracellular endosomal compartment of the Nef+ thymocytes. Moreover, using IVKA we found that the activity of Lck is significantly increased in Nef+ thymocytes but was not further increased upon stimulation by α-CD3ε, α-CD4 or α-CD3ε + α-CD4. Moreover, compared to Nef- controls, Lck kinase in Nef+ thymocytes was resistant to degradation upon stimulation. Examining the status of c-Cbl, the main negative regulator of Lck, showed that c-Cbl localized with Lck poorly, despite his constitutive hyperphosphorylation. This explains the failure of Lck degradation. In addition, we found that upon stimulation, Zap-70 phosphorylation at tyrosine 493 by Lck is decreased, resulting by a decrease of Zap-70 kinase activity and TcR proximal event block. These data indicate that CD4-Lck signaling was interrupted by the presence of Nef.

Keyphrases: Hiv-1, Nef, thymocytes, Lck, Zap-70
On some aspects of coherent risk measures and their applications

The aim of this thesis is to study several aspects of risk measures particularly in the context of financial applications. The primary framework that we use is that of coherent risk measures as defined in Artzner et al (1999). But this is not the only class of risk measures that we study here. We also investigate the concepts of natural risk statistics Kou et al (2006) and convex risk measure Follmer/ and Schied (2002). The main contributions of this Thesis can be classified in three main axes: Capital allocation, risk measurement and capital requirement and solvency. In chapter 2, we characterize risk measures with the Lebesgue  property on bounded càdlàg processes. This allows to present two applications in risk assessment and capital allocation. In chapter 3, we extend the concept of natural risk statistics to the space of infinite sequences. This has been done in order to introduce a consistent way of constructing risk measures for data bases of any size. In chapter 4, we discuss the concept of Good Deals and how to deal with a situation where these pathological positions are present in the market. Finally, in chapter 5, we try to relate all three chapters by extending the definition of Good Deals to a larger set of risk measures that somehow includes the discussions in chapters 2 and 3.

Keyphrases: processus Càdlàg, Coherent and Convex Risk Measure, Lebesgue Property, Càdlàg Process, Capital Allocation, Natural Risk Statistics, Hedging and Pricing, Good Deal, Capital Requirement and Solvency
Le langage humain est-il une adaptation biologique? : un regard critique sur une explication adaptationniste

Pinker and Bloom (1990), two proponents of evolutionary psychology, argue that language has evolved as a biological adaptation for the function of communication. In doing so, they claim to shed light on the origin and evolution of language. This paper proposes a critical analysis of their argument from the point of view of the philosophy of biology. On the one hand, it attempts to clarify Pinker and Bloom’s conception of language in order to better define the trait that is regarded as an adaptation. Thus, this paper brings to the fore several problematic assumptions underlying their conception of language. In this context, the concepts of innateness, modularity, universal grammar and systematicity are addressed in a critical manner. On the other hand, this paper aims to make explicit a key concept of their argument: the concept of adaptation. The analysis shows that the opposition between adaptationism and anti-adaptationism is due, in the present instance, to a divergence in the way biological adaptation is defined. An important distinction has to be drawn between an adaptation resulting exclusively from natural selection in a particular functional context and an adaptation that does not a priori exclude other evolutionary factors such as exaptation. In so far as Pinker and Bloom’s argument allows them to conclude that language is an adaptation only in the second meaning of the term, this paper shows that they are not in a position to provide an account of the origin of language.

Keyphrases: Steven Pinker, Paul Bloom, Adaptation, Sciences cognitives, Steven Pinker, Paul Bloom, Origin of Language, Evolution, Philosophy, Biology, Adaptationism, Cognitive Science, Evolutionary Psychology
La Rapamycine inhibe l’expression de l’ARNm de l’ADAMTS-4 induit par les cytokines dans les chondrocytes articulaires

Introduction: During the pathogenesis of osteoarthritis, the pro-inflammatory cytokines IL-1β (Interleukin-1 beta) and TNF-α (Tumor necrosis factor alpha) stimulate the degradation of aggrecans by aggrecanase-1 or ADAMTS-4 (A disintegrin and metalloproteinase with thrombospondin motif). These cytokines may stimulate several signaling pathways leading to an increased expression of ADAMTS-4 in human chondrocytes. The TIMPs (tissue inhibitor of metalloproteinases) are endogens inhibitors of ADAMTS-4. It has been shown that Rapamycin (an immunosuppressor and an inhibitor of the mammalian target of rapamycin or mTOR) may have beneficial effects in this pathology. Our study investigates the impact of Rapamycin on cytokine-induced expression of ADAMTS-4, his implication in certain signaling pathways, and his effects on the expression of TIMP-3. Methods: Human chondrocytes were pretreated with different doses of Rapamycin either alone or stimulated with IL-β and TNF-α. The effect on ADAMTS-4 expression was examined by RT-PCR analysis and enzyme activity by ELISA. Impact of Rapamycin on the activation of different signaling pathways was measured by Western blot analysis. Results: We have shown that Rapamycin down-regulated pro-inflammatory cytokines-induced ADAMTS-4 mRNA expression in human chondrocytes. The IL-1β-induced-enzymatic activity of ADAMTS-4 was slightly inhibited by Rapamycin. Furthermore, Rapamycin present different effects on pro-inflammatory cytokines-stimulated activation of certain signaling pathways such as MAPKs (Mitogen activated protein kinases), AKT, and P70 S6 kinase. Moreover, Rapamycin partially inhibits TNF-α-induced activation of phosphorylation of ERK1/2 MAPK (extracellular signal-regulated protein kinase MAPK). Thus, Rapamycin inhibit IL-1β-induced activation of phosphorylation of the proteins p38 MAPK, JNK (c-Jun N-terminal kinase), and AKT. Also, Rapamycin inhibit IL-1β and TNF-α-activation of phosphorylation of the protein p70 S6 kinase. In other way, we have shown that the level of TIMP-3 has been increased in the presence of Rapamycin. Conclusion: These results suggest that Rapamycin down-regulates the expression of ADAMTS-4 by inhibiting the cytokine activation of MAPKs, AKT, and p70 S6 kinase. Thus Rapamycin could be considered as potential therapeutic agent for prevention of cartilage loss in patient with osteoarthritis.

Keyphrases: cartilage, ADAMTS-4, chondrocytes, interleukine-1β, tumor necrosis factor alpha, transduction de signal, Osteoarthritis, cartilage, signal transduction, Rapamycin, interleukin-1β