NCube/papyrus huggingface dataset:
Évaluation de la valeur pronostique de la lactatémie et de la troponinémie lors de syndrome vache à terre

Downer cow syndrome (DCS) is observed in dairy cattle and is an emergency condition that progresses rapidly and whose prognosis is reserved to poor. The only available complementary tests require the services of a commercial laboratory. The presence of local and/or systemic hypoperfusion, along with the presence of cardiac lesions at necropsy renders the dosage of lactatemia (LAC) and cardiac troponin I (cTnI) in the blood potentially interesting. These two biomarkers being measurable through the analysis of portable equipment, the present study objective was to evaluate the prognostic value of measuring LAC and cTnl directly at the side of the dairy cow affected by DCS. The percentage of negative outcome (death or euthanasia; NO) seven days following the study inclusion (d7) was 63.1%. LAC was not associated with the prognosis of the animal suffering from DCS. However, a blood cTnl value of ˃0.7ng/mL was associated with a NO before d7 (sensitivity, positive and negative predictive values of 54.1, 78.4, 82.0, and 48.3%, respectively). The use of a logistic multivariable model demonstrated that hypertroponinemia was associated with a NO risk 5.5 greater (95%CI: 2.1-14.6) by d7 than animals presented with a blood cTnl value of ≤ 0,07ng/mL. The animals presenting a HR > 100BPM were 3.7 times more at risk (95%CI: 1.5-10.2) of exiting the herd by d7 than the animals with a HR of ≤ 100BPM.

Keyphrases: Downer cow syndrome, Dairy cow, Lactatemia, Cardiac troponin, Prognosis, First line, Animal welfare
Un nouveau clone et une nouvelle méthode pour la production et la purification de l’entérotoxine STb d’Escherichia coli

The heat-stable enterotoxin b gene (estB) of Escherichia coli was fused to the gene for maltose-binding protein (malE) into the pMAL-p vector using PCR. Afterward, two plasmid constructs were realized from this new vector, named pMAL-STb. Firstly, a hexahistidine tag (His6) was added between malE and estB and secondly, a decahistidine tag (His10) was placed upstream of malE. The signal sequence of maltose-binding protein (MBP) directs the export of the fusion protein from the cytoplasm to the periplasm, where the enterotoxin STb acquires its active conformation. MBP is also known to improve the yield and solubility of the passenger protein while the histidine tag, viewed as the best affinity tag for protein purification, facilitates its purification to homogeneity. Furthermore, the fused genes are controlled by the tac promoter (Ptac), a strong inducible promoter. Following IPTG induction, the recombinant strain expressed a protein of approximately 48 kDa, which is easily identified from osmotic shock fluid following electrophoresis. A sequence encoding a factor Xa cleavage site is present in the plasmid to separate MBP and histidine tags from STb. The cleavage of the fusion protein with factor Xa generates the maltose-binding protein (42 kDa) attached to the histidine tag and a polypeptide of 5.2 kDa, corresponding to the molecular mass of mature STb. With this method, we aim at obtaining a more efficient way to produce and purify STb.

Keyphrases: Escherichia coli, purification, Maltose binding protein (MBP), STb enterotoxin, Decahistidine (His10)
Le groupe sanguin canin Dal : prévalence et immunogénicité

The purpose of this study was to determine the clinical importance of the Dal canine erythrocyte antigen by investigating its prevalence, its mode of inheritance and its immunogenicity. A total of 1230 dogs recruited from North America were blood typed for Dal applying a gel column technique using polyclonal canine anti-Dal sera. Dal-negative dogs were identified mostly in Dalmatians (15/128), Dobermans Pinschers (183/432) and Shih Tzus (12/21), and sporadically in mixed breed dogs (3/122), Beagles (2/100), Lhasa Apso (1/6) and Bichon Frise (1/3). All other dogs tested were Dal-positive (n= 418). Six Dal-negative blood donors were found, including 5 Doberman Pinschers (1/228 non-Dalmatian and non-Doberman Pinscher blood donors). The scarcity of Dal-negative blood donors puts Dal-negative patient at higher risk of transfusion incompatibility if requiring multiple blood transfusions. This study was the first to identify Dal-negative dogs in other breeds than Dalmatians and to establish an autosomal dominant mode of inheritance of the Dal-positive phenotype. Secondly, 2 Dal-negative healthy research Beagles were sensitized specifically for Dal with a Dal-positive packed red blood cell transfusion. Following sensitization, anti-Dal alloantibodies were detected as early as 4 days post-transfusion and remained detectable 2 years post-transfusion, with maximum agglutination titers (1:1024 and 1:64) reached respectively 1 and 2 months posttransfusion in dog #2 and dog #1. Our study confirmed the immunogenicity of the Dal and allowed banking of a considerable amount of polyclonal antisera for further Dal blood typing.

Keyphrases: Dal, Typage sanguin, Transfusion, Crossmatch, Blood typing, Dog erythrocyte antigen, Gel column technology
Développement et caractérisation de modèles C. elegans pour la maladie de Machado-Joseph

Polyglutamine expansion diseases are a class of dominantly inherited neurodegenerative disorders that develop when a CAG repeat in the causative genes is unstably expanded above a certain threshold. The expansion of trinucleotide CAG repeats causes hereditary adult-onset neurodegenerative disorders such as multiple forms of spinocerebellar ataxia (SCA). The most common dominantly inherited spinocerebellar ataxia is the type 3 (SCA3) also known as Machado-Joseph disease (MJD), an autosomal dominant, progressive neurological disorder. The gene causing MJD is ATXN3 (ATAXIN-3): MJD is caused by an abnormal CAG trinucleotide repeat expansion in the ATXN3 gene. Several recent studies have shown that this gene is associated with endoplasmic reticulum (ER) stress. In this study, we generated transgenic C. elegans strains expressing wild type or mutant human ATXN3 genes and tested them for recovery of locomotor phenotype, lifespan and neurodegeneration phenotypes upon treatment with compounds known to modulate ER stress and having neuroprotective roles. We observed differences between both transgenic lines and found that the motility defects, the reduced lifespan and the neurodegeneration can be rescued by methylene blue, guanabenz and salubrinal. These compounds were also able to prevent the oxidative stress and the ER stress response induced by mutant transgenic worms. We introduce novel C. elegans models for MJD based on the expression of full-length ATXN3 in GABAergic motor neurons. Using these models we discovered that chemical modulation of the ER unfolded protein response reduced neurodegeneration and could be a new therapeutic approach for the treatment of MJD.

Keyphrases: ATXN3, C. elegans, Polyglutamine expansion diseases, MJD, Trinucleotide repeats, Neurological disorder, ATXN3, C. elegans, Motility defects, Lifespan, Motor neurons, Neurodegeneration, Oxidative stress,, ER stress, Neuroprotective compounds, ER stress modulators
La biosynthèse et la localisation subcellulaire de l'endothéline 1 dans les myocytes et les fibroblasts ventriculaires cardiaques adultes

Type B endothelin receptors (ETB) are located in the nuclear envelope of adult ventricular cardiomyocytes (ACVMs). In both ACVMs and endothelial cells, endocytosed rhodamine endothelin colocalized with Lysotracker but was not observed at the nuclear membrane. In this study we have characterized the regulation and subcellular localization of endothelin biosynthesis in ACVMs and adult cardiac fibroblasts. In both cell types immunocytofluorescence experiments revealed endothelin-1 immunoreactivity, comprising all stages of peptide maturation, either on or near the nuclear membrane. Endothelin converting enzyme 1 (ECE1) is a metalloprotease that converts big endothelin to the biologically active 21-amino acid peptide. ECE1 immunoreactivity was associated with the T-tubules and nuclear or perinuclear membranes in ACVMs. In contrast, ECE1 immunoreactivity was observed both in the nucleus and the cytosol, but not at the plasma membrane, in passage 3 cardiac fibroblasts. Endothelin-1 mRNA was detected in both cell types. Regulation of endothelin production is primarily at the level of transcription. Application of TGFβ1 increased ET-1 mRNA in ACVMs whereas angiotensin II was effective in increasing ET-1 mRNA in fibroblasts. In AVCMs, the increase in ET-1 mRNA was associated with an increase of intracellular ET-1 peptide and nuclear calcium. These data suggest that endogenous endothelin is available and may activate nuclear ETB in ACVMs in response to extracellular stimuli.

Keyphrases: Endothelin 1, Endothelin receptor B, Endothelin converting enzyme B, Nuclear envelope, Heart
Implication de la protéine tyrosine phosphatase DEP-1/PTPRJ dans la promotion de l’invasion des cellules du cancer épithélial de l’ovaire

Epithelial ovarian cancer (EOC) is the most lethal gynecological cancer. Our laboratory has previously shown that the protein tyrosine phosphatase DEP-1 is involved in Src activation, survival, migration and invasion of endothelial cells in response to VEGF. Studies have shown that Src may be implicated in the progression of epithelial ovarian cancer progression. Thus, we were interested in determining if DEP-1 had a role in the promotion of the Src invasive pathway in EOC. First, we have observed a variable protein expression of DEP-1 in six EOC cell lines, and that there was a positive correlation with invasion in Matrigel. We also showed in RNAi experiments that inhibition of DEP-1expression resulted in the decreased phosphorylation of Src and Cortactin, also loss of Cortactin localisation at the cellular membrane. We also observed dysregulation of other pro-tumoral pathways like EGFR and P65 (NfκB) diminution of phosphorylation. Consequently, DEP-1 depletion resulted in loss of invasive capacities of most of the cell lines, and diminution of chemoresistance in response to Carboplatin. Analysis of DEP-1 in EOC tumors revealed the existence of a positive correlation with an aggressive form of ovarian cancer, high grade status, and poorer survival. These results suggest a positive role of DEP-1 in tumor progression of EOC. Our results show for the first time that DEP-1 is implicated in invasion in vitro, and is associated with the most aggressive form of EOC. Thus, DEP-1 is an interesting therapeutical target for EOC.

Keyphrases: DEP-1, Src, In vitro, In situ, Invasion, tumor progression, immunohistochemistry
Rôle de la chromatine dans la modulation de la réponse aux dommages à l’ADN en présence de stress réplicatif

Sirtuins are a conserved family of NAD+-dependent deacetylases that are involved in various processes. Humans have seven sirtuins (SIRT1-7) and play a role in several cellular pathways, while the budding yeast Saccharomyces cerevisiae has 5 members (Sir2, Hst1-4) and influence several pathways, such as the cell cycle or aging. Lack of sirtuin activity however leads to growth defects, thermosensitivity and spontaneous DNA damage by poorly understood mechanisms. To further characterize this phenomenon, this thesis highlights results obtained from a chemogenetic screen realized by treatment with nicotinamide (NAM), a pan-inhibitor of all sirtuins. Our results indicate that NAM causes strong activation of DNA damage-induced signaling in budding yeast Saccharomyces cerevisiae, and that growth defects are mainly due to histone H3 lysine 56 (H3K56) hyperacetylation, a post-translational modification reversed by sirtuins Hst3 and Hst4. During H3K56 hyperacetylation, the Slx4 protein and PP4 complex are both required for yeast growth by modulating the activation levels of Rad53 kinase during the DDR. Also, preliminary results included in this thesis highlight that proper regulation of homologous recombination, one of DNA repair pathways, is essential for growth in the presence of NAM-induced sirtuin inhibition. Together, our results suggest that chromosome-wide histone deacetylation by sirtuins can modulate DNA damage response in presence of replicative stress.

Keyphrases: Nicotinamide, Sirtuins, Histone H3 lysine 56 acetylation, DNA replication, Chemogenetic screen, Cell cycle, DNA damage-induced response, Rad53 activation pathway, Homologous recombination
Characterization of p120-catenin, a novel RSK substrate in the Ras/MAPK signalling pathway

The Ras/MAPK (mitogen-activated protein kinase) signalling pathway is vital in regulating cell growth, survival and proliferation in response to extracellular signals. Positioned downstream in the pathway, the p90 ribosomal S6 kinase (RSK) family regulates cell invasion by weakening cell-cell adhesion, but the mechanisms involved remain elusive.  In this thesis, I expand upon previous work performed in our lab and identify p120ctn, a major component of adherens junctions (AJ), as a new substrate of the Ras/MAPK pathway. Using a phospho-specific antibody, we demonstrate that p120ctn is phosphorylated on a new phosphorylation site on S320 upon activation of MAPK signalling in a RSK-dependent manner. Furthermore, we show that Ras/MAPK signaling reduces p120ctn binding to N-cadherin, suggesting a new mechanism by which MAPK activity decreases cell-cell adhesion by destabilizing AJs. Finally, we designed and optimized two individual assays to be used in future experiments examining the effects of Ras/MAPK signalling on AJ function.  Taken together, our data identifies RSK as a regulator of p120ctn phosphorylation, and also implicates Ras/MAPK signalling in regulating cell-cell adhesion by destabilizing AJ through p120ctn. Given the role of Ras/MAPK signalling in cancer, this new mechanism may play a role in the development and progression of Ras-driven cancers.

Keyphrases: MAPK, RSK, p120ctn, phosphorylation, adherens junction, cadherin, phosphorylation, cell-cell adhesion
Les conséquences des commotions cérébrales sur la variabilité de la fréquence cardiaque durant le développement

This research project sought to evaluate long-term consequences of sport-related concussions (SRC) sustained during development on cardio-autonomic function. To do so, we compared the heart rate variability (HRV) of adolescents hockey players with a history of one or two sport-related concussion (HOC; n = 39) to the HRV of adolescents hockey players who never incurred a SRC (WHOC; n = 52). Athletes from the HOC group were 26 months (20) away from their last injury. Participants’ electrocardiogram was measured at rest, during and after an exercise session on ergocycle. The exercise session consisted of a 6 minutes incremental warm-up followed by 20 minutes between 60 and 70 % of maximal heart rate and finally a 2 minutes active cooldown. Then, a post-exercise rest of 10 minutes was completed. HRV linear and non-linear measures were calculated before, during and after the exercise session. Natural log of standard deviation of NN intervals (lnSDNN) and natural log of low frequencies (lnLF) were both higher for HOC group in the three conditions (rest, exercise, post-exercise) ( < 0.05). This difference was similar across all conditions. These results suggest that SRC might affect cardio-autonomic function differently during development than during adulthood thus reinforcing the need for specific post-concussion interventions for the developing population.

Keyphrases: adolescents, Sport-related concussion, heart rate variability, development, autonomic nervous  system, exercise, adolescents
Adaptation et généralisation spatiale : étude d’une perturbation visuomotrice triaxiale dans un environnement virtuel tridimensionnel

We explored visuomotor adaptation and spatial generalization in the context of three-dimensional reaching movements performed in a virtual reality environment using a learning paradigm composed of four phases: pre-exposure, baseline, learning, and post-exposure (aftereffect and generalization). Subjects started by performing five reaching movements to six 3D memorized target locations without visual feedback (pre-exposure). Next, subjects performed twelve reaching movements to the learning target with veridical visual feedback (baseline). Immediately after, the 3D visuomotor dissociation (horizontal, vertical and sagittal translations) between actual hand motions and visual feedback of hand motions in the 3D virtual environment was gradually introduced (learning phase). Finally, subjects aimed at the pre-exposure and baseline targets without visual feedback (post-exposure). Although subjects were unaware of the visuomotor perturbation, they showed movement adaptation for each component of the triaxial perturbation, but they displayed reduced adaptation rate along the vertical axis. Subjects persisted in applying the new visuomotor association when the perturbation was removed, but the magnitude of this post-exposure shift was lower along the vertical axis. Similar trends were observed for movement aimed at pre-exposure targets. Furthermore, these post-exposure shifts were, on average, greater along the horizontal and sagittal axes relative to the vertical axis. These results suggest that the visuomotor map may be more adaptable to shifts in the horizontal and sagittal directions, than to shifts in the vertical direction. This finding supports the idea that the brain may employ a modular decomposition strategy during learning to simplify complex multidimensional visuomotor tasks.

Keyphrases: spatial generalization, adaptation visuomotrice, visuomotor adaptation, reaching, planification motrice, motor planning, sensorimotor integration
Performance et réponses ventilatoires lors d'épreuves d'effort à puissance constante ou décrémentée visant à maintenir une consommation d'oxygène maximale

Aerobic endurance is more commonly measured at submaximal rather than maximal work intensities, mainly through constant-power output trials, or time trials. However, real competition conditions are better represented through the ability to sustain the highest power output (PO) for the largest period of time. That implies the use of self-pacing strategies, which leads power output to vary throughout the exercise duration, and can also induce the attainment of maximal oxygen consumption (VO2max), in some cases. The aim of this study was thus to compare the variation of some ventilatory (tidal volume, breathing frequency) and systemic (gross mechanical efficiency, O2 cost) parameters, between two maximal endurance protocols, the first one consisting of a constant-load test (100% MAP) and the second one a decremental test at near-maximal aerobic capacity (> 95 % VO2max). Indeed, compared to a “classical” constant-power output test, a decremental test implies the use of VO2 rather than mechanical PO to control intensity throughout the task, and a higher effort duration. Consequently, we observed that the sustainment of maximal O2 consumption rather than maximal aerobic power (MAP) led to different physiological responses from those usually observed during constant-power output tests. These differences were caracterized by a higher breathing frequency as well as a lower tidal volume during the decremental test, which both reflect a more exagerated tachypneic response, and therefore indicate the existence of a shallower breathing pattern in this type of effort, probably due to a higher ventilatory muscle fatigue. This fatigue could also be expressed through a lower gross mechanical efficiency and a higher O2 cost, despite a progressive decrease of mechanical power as soon as oxygen consumption gets near VO2max.

Keyphrases: VO2max, aerobic endurance, gross mechanical efficiency, O2 cost
Les conséquences juridiques de la coexistence de l’obligation d’accommodement raisonnable et du régime public de réparation des lésions professionnelles

Following the review of the genesis of two fundamental regimes in Quebec labour law, the public system that provides repairs to injured workers, established by the Act respecting industrial accidents and occupational diseases, and the duty to provide reasonable accommodation arising from the right to equality under section 10 of the Quebec Charter, this thesis focuses on the development of the normative conflict and the jurisdictional conflict stemming from the parallel evolution of these two sources of obligations for employers. Both of these are based on the reinstatement of disabled workers and the continuation of their employment relationship. This study proposes to explore the legal consequences of the solution adopted by the Quebec Court of Appeal in Caron’s case, dated June 2015, in which the Court decided to overlay the employer’s duty to accommodate onto the Workers’ Compensation public system. Thus, emphasizing on the role that the right to equality plays in public law and discussing its impact on the separation of powers, this thesis shows the consequences from the approach used in the Caron judgment and its particular results through Canadian constitutional and Quebec quasi-constitutional principles. Furthermore, this significant change gives rise to many difficulties regarding the particularities of administrative law, and more specifically, the role and the limited powers of C.N.E.S.S.T. and T.A.T.-D.S.S.T. Finally, this analysis highlights that the solution held by the Court of Appeal infringes on the balance attempted by the public system based on an important social compromise.

Keyphrases: Discrimination, Right to equality, Duty of reasonable accommodation, Employment injury, Vocational rehabilitation, Right to return to work, Jurisdictional conflict, Hierarchy of sources, Separation of powers, Administrative law
The challenge of industry challenges : the uneasy encounter between privacy protection and commercial expression

This essay uses the example of Industry Challenges - a technique deployed by companies to promote the hiring and advancement of certain members of society - to explore a conflict that could arise in Quebec between the individual’s right to privacy as protected by An Act Respecting the Protection of Personal Information In the Private Sector  and the Personal Information Protection and Electronic Documents Act , and that of an organisation to use personal information relating to its workforce to market itself. It briefly reviews privacy protection in jurisdictions with the greatest legal influence on Quebec and Canada: the European Union, the United States and the United Kingdom (Chapter 2). It demonstrates how a blend of these influences is reflected in the Quebec and Canadian approaches to privacy and how existing privacy legislation might prevent a company from effectively and efficiently responding to Industry Challenges (Chapter 3). Finally, the last two chapters respectively explore the interpretive and legislative amendments that could be made to PPIPS and PIPEDA to enable companies to respond to Industry Challenges (Chapter 4) as well as the possible legal action a company could take on the ground that Quebec’s privacy legislation violates its right to express itself commercially under s. 2(b) of the Canadian Charter of Rights and Freedoms  (Chapter 5).

Keyphrases: Expression commerciale, Quebec, An Act Respecting the Protection of Personal Information in the Private Sector, Canadian Charter of Rights and Freedoms, Commercial Expression, Consumer Activism, Industry Challenge(s), Personal Information Protection and Electronic Documents Act, Privacy, Quebec