NCube/papyrus huggingface dataset:
L’évolution des représentations sur les langues d’élèves plurilingues du 3e cycle du primaire lors de l’implantation d’un projet d’Éveil aux langues

This research documents plurilingual immigrant students’ participation in a two year long Language Awareness Program through which their representations of languages are transformed. The current study is set in a multiethnic elementary school in Montreal. The researcher adopts case study methodology to provide an in depth and detailed description of the evolution of the students’ representations of languages on both an individual and a societal level. The students’ representations of the languages in their plurilingual repertoire are examined as well as their representations of linguistic diversity and languages in general. The results of the implementation of a Language Awareness Program over the course of two years: 1) show positive effects on the students’ representations of linguistic diversity; 2) provide support for the students’ developing positive representations of the languages in their plurilingual repertoire by their greater acceptance of partial competencies in one or more of their languages and their increasing ability to express pride surrounding their plurilingualism; 3) illustrate the development of a variety of strategies adopted by the students to legitimize the integration of languages in their repertoire, specifically those in which they possess only partial competencies, including: the ability to evaluate these competencies, to specify their domain (oral or written expression, oral or written comprehension), to qualify and label them using the recognized terminology (mother tongue, second language, language of origin) and to adapt the formal definitions presented in the Language Awareness Program to describe their plurilingual repertoire; 4) show how the majority of the students’ representations of languages shifted throughout the course of the Language Awareness program from an initial tendency to share widely held social representations, including language stereotypes, to the development of increasingly personal and nuanced perspectives by the end of the project; 5) illustrate the development of higher order vocabulary skills as well as an enhanced interest in other students’ languages for participants with strong or average academic skills; 6) show increased investment in Language Awareness activities and greater participation as of the second year of the project, along with the development of stronger oral language skills (expression of opinions and arguments) for participants with a weaker academic skills; 7) reveal the establishment of a classroom climate that fosters learning and reflection about self and others, including the opportunity to gain deeper knowledge of classmates, to develop listening skills, to express an interest in other students’ languages and to recognize their unique abilities.

Keyphrases: Language awareness, Representations of languages, Linguistic diversity, Plurilingualism, Plurilingual competencies, Immigrant students, Elementary school, Case studies
Enseignement de la géométrie en première secondaire et conceptions d'élèves : une oscillation entre la perception, la mesure et la théorie

This research was conducted in a Quebec classroom environment. It pertains to the teaching and learning of geometry at the outset of secondary school. This context is characterized by a geometry that is not clearly defined from the epistemological point of view in either the secondary cycle one program or in textbooks. We attempted to find firstly, the desired geometric activity and updated by teachers with the proposed problems and, secondly, students conceptions developed by these problems. Using data collected from four classes, we then determined this geometric activity and identified six types of problems from which four were predominant. We also observed students conceptions. The classroom activity gave birth to moments of epistemological hesitance that may have had a certain effect on the development of the students’conceptions.

Keyphrases: Teaching, Geometry, Problems, Geometrical paradigms, Student conceptions
Régulation du complexe constitutif formé par le récepteur opioïde delta et le canal potassique de la famille Kir3

Opioids are the most effective analgesics in the treatment of severe pain. They produce their effects by specifically targeting opioid receptors located all along the pain perception pathway where they modulate the transmission of pain information. Most studies in this area try to characterize the opioid receptor in isolation from any signaling partner. This thesis, on the other hand, shows that the delta opioid receptor (DOR) can form a complex with its G protein and one of its effectors involved in the production of the analgesic effect, the G protein coupled inward rectifying potassium channel (Kir3 or GIRK). Having established the presence of this constitutive complex, we then characterized its stability, modulation and regulation following stimulation with opioid agonists.   First, we characterized the transmission of information from DOR, following its activation by an agonist, to the Kir3 channel. We have noticed that this transmission does not follow the collision model, generally accepted, but rather requires a simple change in the conformation within the preformed complex. Then, we have determined that even following prolonged DOR activation by a full agonist, the DOR/Kir3 complex maintained its integrity and was recognized by βarrestin (βarr) as a single signaling unit producing the internalization of DOR and Kir3 by a clathrin and dynamin-dependent mechanism.   Thus, taken together, these data show that DOR activation triggers not only activation of the Kir3 effector but also a regulatory mechanism that removes this effector from the plasma membrane.

Keyphrases: Conformation, Multimeric complexes, Delta opioid receptor, Kir3 channels, G protein, βarrestin, Internalization, Desensitization, Conformation, Analgesia, Tolerance
Le maintien de la stabilité génomique du plastide : un petit génome d’une grande importance

The plant plastidial genome is constantly threatened by many mutagenic stresses, such as base oxidation and replication fork stalling. Despite these threats, the plastid genome has long been known to be more stable than the nuclear genome, suggesting that alterations of its structure would have dramatic consequences on plant fitness. At the moment, little is known about the genes and the pathways allowing such conservation of the organelle genome sequences. To gain insight into these mechanisms, we developed an assay which uses ciprofloxacin, a gyrase inhibitor, to generate DNA double-strand breaks (DSBs) exclusively in plant organelles. By screening mutants deficient for proteins composing the plastid nucleoid on ciprofloxacin, we were able to identify 16 candidate genes, most likely involved in the repair of DSBs in plastid. Among these genes, those of the Whirly family of single-stranded DNA binding proteins are shown to be key factors in protecting the genome from error-prone microhomology mediated repair (MHMR). Two other family of proteins, the plastid type-I polymerases and the plastid recombinases, seem to be involved in the conservative repair pathways. The evaluation of the epistatic relationship between those two genes and the Whirly genes led us to define the molecular basis of MHMR and to propose that they might act as a backup system for conservative repair pathways. Finally, a non-biased screen, using 50,000 different insertion lines, allowed the identification of numerous genes that were already associated with ROS homeostasis, suggesting a link between DNA repair and ROS imbalance. Globally, our study shed light on the mechanisms that allow the maintenance of plastid genome, while explaining the importance of such conservation of the plastid genome.

Keyphrases: Plant Biology, Plastid, Genome, Genomic Rearrangement, DNA Repair, Genomic Stability, DNA Double-stranded Breaks, Next-generation Sequencing
Caractérisation biochimique du complexe Smc5-6

The Smc5-6 complex is part of the SMC (Structural Maintenance of Chromosomes) family and is involved in the maintenance of genome integrity. This complex is required for the replication and repair of DNA. Unfortunately, the DNA substrates recognized by the Smc5-6 complex are still unknown. To address this gap, I used a biochemical approach to purify and functionally characterize the core of the Smc5-6 complex represented by the two SMC proteins. Subsequently, I wanted to understand which part(s) of Smc5 or Smc6 mediate their binding to DNA.   I show here that Smc5 and Smc6 bind to all types of DNA tested. Despite this ability to associate with several types of nucleic acids, they have a clear preference for single-stranded DNA (ssDNA). The ability of Smc5 and Smc6 to link DNA independently of each other suggests that both SMC proteins have the potential to target the Smc5-6 complex to its DNA substrates in vivo. Furthermore, the minimal length of ssDNA required for the binding of Smc5 or Smc6 is between 45 to 75 nucleotides. This length of ssDNA is shorter than the size of ssDNA intermediates created during DNA repair or replication reactions. In addition to having a preference for ssDNA, the binding of both SMC proteins to this type of DNA is stronger than their binding to double-stranded DNA (dsDNA). Finally, the molecular dissection of SMC proteins into functional domains revealed that there are two independent DNA-binding sites on each molecule of Smc5 or Smc6. The first region is located in the hinge domain, while the second region is located in the ATPase head of the protein. The affinity and selectivity of independent domains towards DNA substrates suggest a functional differentiation between the two DNA-binding sites of SMC molecules. Indeed, the hinge domain has a greater affinity for ssDNA than the ATPase head. In terms of selectivity, the hinge domain is capable of binding to dsDNA whereas the ATPase head cannot.    Taken together, our identification of the DNA-binding domains on Smc5 and Smc6 will enable the creation of new mutants with a defect in their DNA-binding activity. Thus, the study of the Smc5-6 complex during DNA repair, in vivo, will be facilitated.

Keyphrases: Structural maintenance of chromosomes, Smc5-6, Genomic stability, DNA double-strand break, homologous recombination, DNA-binding
Étude de la régulation de l'activité du ligand Delta dans le cadre de la signalisation Notch

The Notch signalling pathway is evolutionarily conserved. It plays a key role in development and it is involved in multiple cell fate decisions, in the maintenance of stem cells, and in the regulation of cell proliferation and differentiation. Misregulation of Notch signalling is implicated in various diseases and cancers including solid tumours, such as breast and cervical cancers, and leukemias, such as T-cell Acute Lymphoblastic Leukemia (T-ALL). Notch is a transmembrane receptor activated by transmembrane ligands of the DSL family (Delta/Serrate/Lag-2). Whereas oncogenic mutations have been identified in the Notch receptor, many Notch-mediated cancers remain ligand-dependent. Strikingly, the molecular mechanisms that regulate ligand activation are still poorly characterized as compared to those regulating the Notch receptor itself. Using a co-culture assay with a luciferase Notch reporter, we performed the first genome-wide RNAi screen aiming specifically at identifying regulators of Notch ligands in the signal-sending cell. We thereby unraveled new classes of common regulators for both Delta-like1 and 4 ligands. These regulators include protease inhibitors, transcription factors and various genes of unknown function such as Tmem128 (Transmembrane protein 128), or of previously characterized function such as the molecular co-chaperone Cdc37 (Cell division cycle 37 homolog). We next developed functional secondary screens where we demonstrated that our hits are important for Notch-mediated events, such as normal T-cell differentiation, and survival of pre-leukemic stem cells (pre-LSCs) isolated from a mouse model of T-ALL. Moreover, we showed that top hits from the pre-LSC survival screen are also required for the self-renewal activity of pre-LSCs. Finally, we performed a preliminary molecular characterization of two newly identified regulators; Tmem128 and Cdc37 in order to investigate their mechanism of action on Delta-like ligands. Altogether, this study led to the identification of novel Notch pathway regulators that could serve as potential therapeutic targets in Notch cancers, as exemplified by the T-ALL model. Elucidating the finer details that underlie the molecular functions of these regulators will be critical to develop pharmacological inhibitors to counteract their action and impede Notch signalling in cancer.

Keyphrases: Notch, Delta-like, Screen, Protease inhibitors, Tmem128, Cdc37, T-cell differentiation, T-ALL
Identification de biomarqueurs de risque à la pancréatite aigüe récurrente dans l’hyperchylomicronémie familiale

Familial hyperchylomicronemia is a monogenic trait characterized by an increased fasting plasma triglyceride levels ≥ 10 mmol/L (normal is 1.7 mmol/L). Familial hyperchylomicronemia is most often caused by a deficiency in the LPL gene. Lipoprotein lipase deficiency (LPLD) is also associated with an increased risk of pancreatitis. Pancreatitis is recognized as a complex genetic trait and several genes are associated with its susceptibility. Considering the variable expression of pancreatitis in LPLD patients, results of this manuscript demonstrate that genetic factors may be responsible of the increased risk of recurrent acute pancreatitis episodes in LPLD subjects. The sequencing analysis of the coding and promoters regions of CTRC gene (for Chymotrypsin C) and SPINK1 gene (for Serine protease inhibitor Kazal type 1) was performed. These two genes encode proteins involved in the metabolism of the pancreas proteases and have been associated with pancreatitis in literature. A combination of two polymorphisms (CTRC-rs545634 and SPINK1-rs11319) have been identified and associated with recurrent hospitalizations for severe abdominal pain or recurrent acute pancreatitis in LPLD patients (p <0.001). These results suggest that the risk of recurrent episodes of pancreatitis in LPLD patients may be influenced by variants in susceptibility genes. The identification of genetic biomarkers improves the understanding of the pathophysiological mechanisms of pancreatitis in LPLD patients which therefore helps to assess and characterize the risk of pancreatitis to adapt preventive intervention plan for these patients.

Keyphrases: Lipoprotein lipase, Familial hyperchylomicronemia, Lipoprotein lipase deficiency, Severe hypertriglyceridemia, Pancreatitis, SPINK1, CTRC, Genetic biomarkers
Vers une prise en charge améliorée des patients avec glycogénose : nouvelles approches diagnostique et thérapeutique

Glycogen storage diseases are diseases affecting glycogen synthesis or degradation. Early diagnosis and optimal diet, including hypoglycemia prevention, are essential for better patient outcomes. The present work aimed to genetically confirm glycogen storage disease in Inuit from Nunavik and to evaluate the impact of a new nutritional therapy, GlycosadeTM, on sleep and quality of life in a cohort of patients from Montreal.   We identified the causative mutation of glycogen storage disease in Nunavik by means of exome sequencing allowing early diagnosis and screening of family members. We also introduced a long acting form of cornstarch and prospectively assessed sleep and quality of life before and after this treatment in patients with glycogen storage disease. We highlighted sleep disturbances in patients and discussed GlycosadeTM as a promising therapeutic option.

Keyphrases: Exome, Glycogen storage diseases, Inuit, Sleep, Quality of life, Cornstarch, Continuous glucose monitoring
Analyse préliminaire du rôle des "Ubiquitin specific peptidases" et de l'axe USP7-MDM2-TP53-CDKN1A dans les leucémies myéloïdes aiguës

There is a high rate of drug resistance in acute myeloid leukemia (AML) which may be associated with TP53 alterations. The « Ubiquitin specific peptidases » (USP) are involved in several cancers but their roles in AML are not elucidated. Gene expression analysis of 21 USP and genes of the USP7-MDM2-TP53-CDKN1A axis by quantitative RT-PCR in 111 AML samples, showed a deregulation of USP44, USP1, USP28 and CDKN1A in respectively 72%, 44%, 25% and 42% of cases. CDKN1A, an important TP53 target, may have a role in treatment resistance. We have developed an experimental model to assess the response of leukemic cells to doxorubicin and nutlin 3, a non genotoxic TP53 modulator, in relation to the CDKN1A expression level. This preliminary work suggests that some members of the USP family and CDKN1A could represent novel therapeutic targets in AML.

Keyphrases: "Ubiquitin specific peptidases" (USP), TP53, CDKN1A, Acute myeloid leukemia, therapeutic targets
Les admissions hospitalières pour les infections urinaires: tendances temporelles, fardeau économique et facteurs prédicateurs de mauvaise évolution des patients

Abstract Introduction: Urinary tract infections (UTIs) are the most common bacterial infections in hospitalized patients. This study describes the temporal trends of admissions and mortality, as well as the economic burden of UTI-associated hospitalizations. Predictors of having severe disease as well as predictors of mortality were also examined. Methods: Data were retrieved from the Nationwide Inpatient Sample between 1998 and 2010, yielding a weighted sample of 1,717,181 UTI-associated admissions. Incidence and mortality rates were calculated and stratified according to gender, age, and the presence of sepsis. The median and total charges of hospitalization were calculated and adjusted for inflation. Finally, predictors of UTI induced sepsis and mortality were examined using logistic regression models.  Results: The overall incidence and mortality of UTI-admissions has been increasing with an EAPC of +4.764 and +4.610 respectively (p<0.0001). The increase of UTI-admissions is most remarkable for patients aged 55-64 years (EAPC = +7.805; p<0.0001). Median cost per hospitalization has increased from $10,313 in 1998 to $21,049 (EAPC +9.405; p<0.0001). Overall total inpatient yearly cost rose from $8.9 billion in 1998 to $33.7 billion in 2010 (EAPC +0.251; p<0.0001). Increasing age, male gender, African-American race, patients with Medicaid or no insurance and those treated at non-academic centers are at increased risk of UTI-associated inpatient mortality (p<0.0001). Conclusion: The incidence and mortality of UTI-associated hospitalization has increased over the last decade. The inflation-adjusted median cost of UTI-hospitalization as well as the total overall annual associated cost have been steadily increasing. In these patients, male gender, African-American race, those with Medicaid or no insurance and those treated in non-academic hospitals represent attributes associated with higher risk of mortality. These findings represent candidate quality indicators to adapt health care policy for particularly vulnerable sub-populations.

Keyphrases: sepsis, Urinary tract infection, hospitalization, cost, mortality, outcomes
Parental projections of developmental outcome, quality of life and coping in children who require neonatal intensive care

In the neonatal intensive care unit, professionals and parents prognosticate about developmental and quality of life (QOL) outcomes. The purpose of this thesis is to understand how parents predict future QOL for their babies during the neonatal period.   In a qualitative study using grounded theory, ten interviews with parents were conducted. The main findings indicate that developmental prognosis influences parental predictions of QOL but it is not sufficient in defining it, since QOL is a multidimensional construct. Parents use a variety of coping mechanisms in dealing with the adversity arising from the illness and hospitalization. Parents who believed that they and their child would be able to adapt to an eventual poor developmental outcome predicted a re-framed QOL.   Neurodevelopmental prognosis and future QOL are not easily estimated and health professionals should be acutely aware of this. Helping parents identify coping mechanisms might lead to more positive prognosis of future QOL.

Keyphrases: Recherche qualitative, Quality of life, Neonatology, Prognosis, Uncertainty, Development, Qualitative, Grounded theory, Resilience, Coping
L'expression de nestine est associée à l'entrée des cardiomyocytes de rats néonataux dans le cycle cellulaire

Myocardial infarction is one the possible outcomes of cardiac ischemia and is characterized by cardiomyocyte death downstream of the site of occlusion and subsequent scar formation by myofibroblasts secreting extracellular matrix proteins. Nestin is a class VI intermediate filamentous protein associated with cellular proliferation and migration. Following a myocardial infarction, striated nestin protein expression was detected in a subpopulation of cardiac myocytes bordering the peri-infarct/infarct region of the rodent and human heart. The primary goal of the present thesis was to determine the cellular source of the nestin(+) cardiac myocytes selectively observed in the myocardial infarcted heart and the underlying signalling events implicated in nestin expression. Employing a transgenic approach, the appearance of nestin(+) cardiac myocytes in the infarcted mouse heart was not attributed to the differentiation of nestin(+) neural progenitor/stem cells. The treatment of neonatal rat ventricular myocytes with the protein kinase C (PKC) activator PDBu and the concomitant inhibition of the p38 MAPK pathway markedly increased the percentage of cells expressing nestin. Furthermore, a significant population of nestin-expressing neonatal rat ventricular myocytes incorporated bromodexoxyuridine, revealing an ability to re-enter the cell cycle and undergo DNA synthesis. On the basis of these observations, the appearance of nestin(+) cardiac myocytes in the infarcted rodent and human heart may reflect a subpopulation of proliferating cardiomyocytes attempting to regenerate the ischemically damaged heart.

Keyphrases: p38 MAPK, Myocardial infarction, Protein kinase C, p38 MAPK, Cardiac regeneration
Neuropsychological predictors of treatment outcome in obsessive compulsive disorder (OCD)

Background: Despite substantial evidence supporting the general efficacy of cognitive behavioral therapy for obsessive-compulsive disorder (OSD), there is controversy about improvement in some neuropsychological deficits in this disorder. Objective: The present study aim to evaluate: 1) correlation of severity of OCD and neuropsychological test scores and 2) clinical and neuropsychological improvement of patients with OCD who have successfully completed their treatment. Method: This study evaluates neurocognitive function and clinical condition of 27 participants of OCD group and 25 participants of control group. The neurocognitive function of every participant has been assessed using Rey-Osterreich Complex Figure Test (RCFT), D-KEFS fluency test and Cardebat- D test. We also, used Beck Anxiety Inventory (BAI), Beck Depression Inventory (BDI) and Yale-Brown Obsessive-Compulsive scale(Y-BOCS) to verify comorbidity of anxiety and depression with OCD and severity of symptoms in patients with OCD. Results: Our study concludes that a significant difference of function in copy score is present between OCD and control group. Also, we found considerable difference in score of immediate and delayed recall of RCFT before and after treatment in OCD group. Conclusion: In summary, the present study demonstrated that OCD patients have specific cognitive impairments and cognitive behavioral therapy could improve, at least, some neurocognitive dysfunction.

Keyphrases: OCD, Neuropsychological tests, Cognitive behavioral therapy, Predictors, Comorbidity, Anxiety, Depression