NCube/papyrus huggingface dataset:
Les cellules stromales multipotentes accélèrent la guérison de plaies cutanées chez les souris irradiées via la sécrétion de la chimiokine SDF-1α

Cancer treatment using ionizing radiation (IR) may lead to significant side effects, like delayed tissue repair and regeneration. The mechanisms mediating these defects remain largely unknown at present, thus limiting the development of therapeutic approaches. Using a wound healing model, we investigate the mechanisms by which IR exposure limits skin regeneration. Our results show that induction of the stromal-derived growth factor 1α (SDF-1α), a cytokine normally overexpressed in hypoxic tissues, is severely impaired in the wounded skin of irradiated, compared to non-irradiated, mice. This defect is correlated with delayed healing, and is evident for several months following exposure to IR, suggesting permanent impairment of skin repair.  Because SDF-1α is secreted mainly by dermal fibroblasts, we evaluated the potential of multipotent stromal cells (MSCs), which secrete high levels of SDF-1α, to improve skin regeneration in irradiated mice. Injection of MSCs into the wound margin led to remarkable enhancement of skin healing in mice exposed to IR. The MSC actions were mainly paracrine, as the cells did not migrate away from the injection site or differentiate into keratinocytes. Specific knockdown of SDF-1α expression led to drastically reduced efficiency of MSCs in improving wound closure, indicating that SDF-1α secretion by MSCs is largely responsible for their beneficial action. We also found that one mechanism by which SDF-1α enhances wound closure likely involves increased skin vascularization.  Findings presented in this thesis collectively indicate that SDF-1α is an important deregulated cytokine in irradiated wounded skin, and that the decline in tissue regeneration potential following IR can be reversed, given adequate microenvironmental support.

Keyphrases: SDF-1α, radiation ionisante, MSCs, ionizing radiation, wound healing
Les TOD dans la région de Montréal : la demande et les barrières à l'offre

Transit-oriented development or TOD is an urban planning concept that is often proposed as a solution to the problems associated with suburban sprawl. The majority of research on this concept is descriptive; some authors examined the effect of TOD pro-jects on travel behaviour. A new research approach proposes to investigate the rarity of examples of veritable TOD in North America. This approach proposes that the lack of examples is either the result of a weak demand, or of a variety of supply barriers catego-rized as financial, regulatory, political, organizational or pertaining to the physical con-text of the city. Our study applies this research approach in order to examine the development of TOD in the Montreal metropolitan region. The empirical study focuses on the perspec-tive of real estate developers regarding the degree of demand and the supply barriers to TOD. The methodology consists of interviews with a diverse group of real estate devel-opers working in the Montreal suburbs. The results demonstrate that the demand is growing for products having certain characteristics of TOD, but that this does not reveal a demand specifically for TOD. We also determine that the two principal supply barriers are the lack of land and the insufficient supply of public transit service. Other major obstacles include lack of a common definition of TOD and the structure of the land de-velopment industry which is not well adapted to this form of development. The study concludes that the realization of TOD in the Montreal context requires that provincial and municipal government actors assume a more proactive and visionary role.

Keyphrases: TOD, transit oriented development, alternative development, supply, demand, barrier, developer
Diminution de la performance motrice du membre ipsilatéral au site de l’accident vasculaire cérébral lors de tâches bilatérales

As a result of a cerebrovascular accident (CVA), deficits in the controlateral and ipsilateral limb of the brain lesion are observed in person who had had a CVA. The performance of the ipsilateral limb is determined by the clinical severity of the contralateral limb and by the adequacy of bi-hemispheral processing of information. The objective of the present study is to compare the motor performance of the ipsilateral hand during tasks implying different level of sensori-motor integration in patients with low clinical impairments. The results demonstrated that the pinch strengths between the thumb and the index finger of the ipsilateral limb are modulated and anticipated adequately in stroke persons who have a good motor recovery such as demonstrated by scores of five or more in the Chedoke-McMaster Stroke Assessment (arm and hand parts). The motor performance of the ipsilateral limb of stroke persons during the execution of a bilateral coordination task is comparable to the motor performance of the dominant limb of healthy subjects when the task is realized without interaction between upper limbs (two objects) and it is perturbed when it implies a coordinated and reciprocal action of upper limbs on the same object. Consequently, these stroke persons with a good motor recovery have a central problem of integration and processing of sensori-motor informations when a more complex task has to be realized. These results suggest that the clinicians should pay more attention during unilateral tasks and during tasks with bilateral coordination that require a higher level of sensori-motor integration.

Keyphrases: Cerebral vascular accident, Upper limbs, Grip force, Load force, Sensori-motor integration
Activités antidiabétiques et neuroprotectrices du jus de bleuet biostransformé

Blueberry demonstrates therapeutic potential against cancer, cardiovascular and neurodegenerative diseases. These desirable effects are thought to involve abundant phenolic compounds in blueberry such as anthocyanins and flavonoids. Blueberry juice biotransformation by Serratia vaccinii bacteria increases its phenolics content, its antioxidant activity and modifies its physiological properties. The purpose of the present study was to evaluate the neuroprotection activity and the antidiabetic potential of biostranformed blueberry juice (BJ). BJ was studied for: 1) Protection of neurons (N2a) against oxidative stress caused by hydrogen peroxide; 2) Stimulation of glucose uptake by muscle cells (C2C12) and adipocytes (3T3-L1); 3) Anti-hyperglycemic activity in diabetic obese KKAy mice. Indeed, whereas normal blueberry juice did not show any effect, BJ increased antioxidant enzymes activities (catalase, SOD) and protected neurons against modifications in MAPKs pathways and toxicity induced by hydrogen peroxide. BJ also increased glucose uptake by 48% in C2C12 cells and by 142% in 3T3-L1 cells. Enhanced glucose uptake could not be explained by an increase of cytosolic calcium but was related to the stimulation of AMPK phosphorylation. Moreover, BJ inhibited 3T3-L1 adiopogenesis. BJ also reduced hyperglycemia of obese diabetic KKAy mice and protected pre-diabetic young mice against the development of obesity and diabetes mellitus. The anti-hyperglycemic effect of BJ may involve adipokine pathways since BJ increased adiponectin levels in diabetic mice. Thus, BJ represents a promising approach for the prevention and treatment of diabetes mellitus and possibly neurogenerative diseases as well as a source of novel therapeutic agents against these disorders.

Keyphrases: Neuroprotection, Serratia vaccinii, Biotransformation, Diabetes, Obesity, Adiponectin, Antioxidant, Blueberry juice
Encapsulation de Dehalococcoides: avantage pour la déhalogénation des solvants chlorés en sites contaminés

Tetrachloroethylene (PCE) and other chlorinated ethenes have been used for industrial purposes since the beginnning of 20th century. However, they are now considered common pollutants of soil and water. A lot of efforts are directed toward elimination of these compounds and we believe degradation of these chlorinated ethenes by microorganisms is the best solution. The first step of this project was to establish a complete conversion of PCE to its non-toxic product ethylene using an enriched consortium of Dehalococcoides ethenogenes. Our results show the importance of lactic acid as a carbon source and indirect source of electrons in a reaction known as dehalorespiration. We have been able to establish the effect of initial biomass on the biodegradation profile of PCE. The second step of the project was to obtain a working protocol for encapsulation of the consortium in a polymeric matrix. Such immobilization procedure would then allows numerous possible advantages as shown in the literature. We tested three encapsulation setups: air atomization, ultrasonic atomization and drop-wise technique. In the last setup, we successfully encapsulated the bacterial consortium into particles made of an alginate core surrounded by a chitosan layer. Thus the drop-wise technique allowed encapsulation of the consortium without negative effects on its dechlorination activity. In addition, the dechlorination profiles of encapsulated cells showed a lower accumulation of chlorinated intermediates TCE, 1,2-DCE and VC which yield a more rapid and complete conversion of PCE to ethylene. Finally, our results support the idea that encapsulated microorganisms may benefit from a protective effect when oxygen is present in the medium.

Keyphrases: Encapsulation, Bioremediation, Alginate, PCE
Les effets d’un traitement au corticostérone sur la transmission dopaminergique mésocorticale du rat en période de stress

The hypothalamic-pituitary-adrenal axis plays an essential role in responding and adapting to stress, however overactivation of this axis or chronically high levels of glucocorticoids lead to pathological outcomes. The mesocortical dopamine (DA) system, terminating in the medial prefrontal cortex (mPFC), plays an adaptive role in protecting against stress, yet the functional interactions between glucocorticoids (eg. corticosterone) and the mesocortical DA system are not clear. In the present studies, we investigated the effects of glucocorticoids on prefrontal DA function using osmotic minipumps to chronically elevate corticosterone levels in the high physiological range (1 mg/kg/hr for 7 days). Chronic corticosterone treatment did not significantly affect post mortem levels of DA and its metabolites in PFC tissue in either unstressed or stressed rats. However, using in vivo voltammetry to monitor changes in extracellular DA release in PFC, corticosterone significantly increased DA release in response to both types of stress examined, exposure to predator odor and tail pinch stress. We conclude that corticosterone indeed potentiates mesocortical DA function, which in turn facilitates negative feedback regulation in times of stress.

Keyphrases: Stress, Dopamine, Glucocorticoids, Prefrontal cortex, Hypothalamic-pituitary-adrenal axis, Corticosterone, Mesocortical dopamine system
Représentation et recherche de motifs cycliques et structuraux d’ARN connus dans les structures secondaires

Deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) are polymers of nucleotides essential for the survival of the cell.  Contrary to DNA, whose main role is to store genetic information, RNA is involved in multiple metabolic processes.  For example, RNA is involved in the transfer of information from DNA to protein, the processing and modification of other RNAs, the regulation of gene expression, the end-maintenance of chromosomes, and the sorting of proteins within the cell.  This functional versatility of RNA comes from its structural diversity.  Our laboratory developed MC-Fold, an algorithm that predicts RNA structures by representing them with nucleotide interaction graphs.  The nodes in these graphs represent the nucleotides, and the edges the interactions between them.  Our laboratory also observed that a limited number of interaction cycles can define the structure of any RNA motif.  The formation of these cycles is determined by the nucleotide sequence and MC-Fold determines the most likely cycles based on that sequence.   In this Master Degree project, I first built a database of structural and functional RNA motifs, bdMotifs, based on their constituent cycles.  Then, I implemented an algorithm, MC-Motifs, which detects motifs within interaction graphs generated either by MC-Fold or by any other method.  Finally, I validated my algorithm on known RNA structures such as the 5S, 16S and 23S ribosomal RNA (rRNA) and predicted structure of riboswitches.   The Master thesis is divided into five chapters.  The first chapter presents the chemical structure of RNA, its cellular functions and the structural folding of the polymer.  In the second chapter, the database bdMotifs is described.  In the third chapter, the MC-Motifs algorithm is introduced.  In the fourth chapter, I present the results of MC-Motifs.  Finally, in the last chapter, I discuss theses results and I give a conclusion on the project.

Keyphrases: Motif, Cycle, RNA, Secondary structure
Mutations du gène HFE dans le cancer épithélial de l'ovaire

Epithelial ovarian cancer is the most aggressive gynecological cancer with the highest mortality rates. Growth of the ovarian cancer cells is limited by nutrients in the environment; iron being one of the elements essential to their proliferation. Hereditary hemochromatosis is a disease associated with an accumulation of body iron, and is linked to two mutations of the HFE gene including C282Y and H63D. Given the influence of HFE protein on the entry of iron in the cell, mutations in the HFE gene may be associated with rapid growth of cancer cells. By genotyping the HFE gene of 526 patients with epithelial ovarian cancer, we have found that the allelic frequency of the C282Y mutation is significantly higher in patients with ovarian cancer compared to patients in the control group (5.9% versus 1.3% p = 0.02). Moreover, the 2-year survival rate, of patients with C282Y mutations and G3 ovarian tumor, is low (20%) when compared to patients without mutations (60%, p = 0.005). A multivariate survival analysis, using Cox’s regression model, also showed a hazard ratio value of 3.1,suggesting that patients with the C282Y mutation are 3 times more likely to have a poor survival (p =0.001). As well, correlation studies have demonstrated that serum ferritin levels were higher in patients with advanced grade of ovarian cancer (r = 0.445 and p = 0.00001), suggesting that this iron parameter could serve as a tumor marker for assessing the progression of ovarian cancer. In order to investigate these findings, we first studied the influence of HFE mutations on cancer cells. The ovarian cancer cell line TOV-112D, homozygous for the C282Y mutation, was transfected with the HFEwt and HFEC282Y vector, and although there were no differences in total TfR levels, FACS analysis demonstrated an iron deficient phenotype for the HFEwt stable clones (p<0.05). In vitro,restoration of the HFE protein, in the TOV-112D ovarian cancer cell line, does not influence cell growth. We then studied the influence of iron levels on tumor progression. A preliminary in vivo experiment has demonstrated a tendency to a higher tumor volume in a mouse model of iron overload,HfeRag1-/-. Furthermore, HfeRag1-/- mice that were injected with the ovarian cancer cell line TOV-21G showed significant lower serum iron levels compared to their controls (SI 40±7μM versus 27±6μM, p = 0.001). In conclusion, more studies are required to further understand the role of HFE mutations on tumor progression. Higher iron levels may confer tumor cells to be drug resistant or increase toxicity and thus, may contribute to a bad prognostic.

Keyphrases: Fer, HFE, Mutations, C282Y, HfeRag1-/-, Ovarian Cancer, Iron, HFE, Mutations, Proliferation, C282Y, Tumor marker, Ferritin, HfeRag1-/-
Doing Justice to Recognition

The traditional role of justice is to arbitrate where the good will of people is not enough, if even present, to settle a dispute between the concerned parties. It is a procedural approach that assumes a fractured relationship between those involved. Recognition, at first glance, would not seem to mirror these aspects of justice. Yet recognition is very much a subject of justice these days. The aim of  this paper is to question the applicability of justice to the practice of recognition. The methodological orientation of this paper is a Kantian-style critique of the institution of justice, highlighting the limits of its reach and the dangers of overextension. The critique unfolds in the following three steps: 1) There is an immediate appeal to justice as a practice of recognition through its commitment to universality. This allure is shown to be deceptive in providing no prescription for the actual  practice of this universality. 2) The interventionist character of justice is designed to address divided relationships. If recognition is only given expression through this channel, then we can only  assume division as our starting ground. 3) The outcome of justice in respect to recognition is identification. This identification is left vulnerable to misrecognition itself, creating a cycle of injustice that demands recognition from anew. It seems to be well accepted that recognition is essentjustice, but less clear how to do justice to recognition. This paper is an effort in clarification.

Keyphrases: Justice
Virus-Host Interaction during Therapy against Hepatitis C Virus

Hepatitis C virus (HCV) is a major public health problem worldwide.  Only 15-30% of infected individuals clear the virus spontaneously, while the majority develops chronic infection that causes liver complications. The only approved therapy for HCV is interferon alpha (IFN-α) based. This therapy has a 50-80% success rate depending on the infecting virus genotype and the timing of initiation of therapy. Factors governing the response to therapy are not well defined.  Previous studies have suggested a role for the host immune response in the success of therapy. However, these results were controversial.   We hypothesized that host immunity has an effective role in the success of IFN-α therapy when initiated early during the acute phase of HCV infection, while late initiation during the chronic phase minimizes this role. The main objective of this thesis was to dissect the immunological factors governing the differential response to IFN-α therapy, and to determine if the contribution of the immune response to success of therapy might be influenced by the period of infection.   Our results demonstrate restoration of efficient HCV-specific immune responses when therapy is initiated early during the acute phase. This is demonstrated by the rescue of functional HCV-specific T cells similar to those observed in spontaneously resolved individuals, suggesting that they may play an active role in response to therapy. However, such responses were not restored following late therapy suggesting irreversible damage to the host’s defence system with chronicity. These findings have important implications in understanding the mechanisms underlying response to current treatments and development of novel therapies.

Keyphrases: Hepatitis C Virus (HCV), Interferon alpha (IFN-α), adaptive immunity, acute infection, chronic infection
Caractérisation moléculaire et fonctionnelle de Cif1p, une protéine orpheline impliquée dans le phénomène épigénétique de viabilité de la levure S. pombe en absence de la chaperone calnexine

Protein folding is a vital process that involves many proteins of the cell. One of them is calnexin, a chaperone of the endoplasmic reticulum. In the fission yeast Schizosaccharomyces pombe, calnexin is essential for survival of the cells. During structure-function studies on calnexin, our laboratory discovered a phenomenon allowing the viability of cells without this chaperone. This state, designated Cin for Calnexin INdependence, is induced by a calnexin mutant devoid of the highly conserved central domain (Δhcd_Cnx1p). Characterization of the Cin cells showed several exceptional properties such as dominance, non-Mendelian transmission and transmission via cell extracts devoid of nucleic acids of the Cin state. All these observations suggested that the Cin phenomenon is mediated via a prionic element.   To identify genes implicated in the Cin state, genetic screens were performed. They led to the identification of the cif1+ gene, for calnexin independence factor. This gene encodes an orphan protein, the overexpression of which stably induces a state of viability in the absence of calnexin. Notably, this state is genetically and phenotypically distinct from the previously isolated Cin state arising from Δhcd_Cnx1p expression. This suggests the presence of two parallel pathways both able to signal the induction of the Cin phenomenon. The exhaustive characterization of Cif1p showed that it is not the prion solely responsible for the Cin state, although it displays prion-like properties in vitro. Finally, nucleolar localization of Cif1p is required to induce the Cincif1 state, thus suggesting an unexpected interaction between the vital cellular role of calnexin and a function of the nucleolus.   While investigating Cif1p function in the cell, we observed that it interacts with ribosomal proteins of the large subunit, notably L3, but it does not sediment with assembled ribosomal subunits or whole ribosomes.  However, cells containing a genomic deletion of cif1 also have a disrupted ribosome content during stationary phase. Altogether, these results suggest that Cif1p has a role in ribosomal biogenesis during stationary phase. This growth-phase specific role correlates with the occurence during stationary phase of a cleavage in the N-terminal part of Cif1p. Recent studies from our laboratory proposed that calnexin plays an important role in apoptosis signaling, especially in stationary phase. Thus, a pathway implicating Cif1p, its nucleolar function in ribosome biosynthesis in stationary phase, calnexin and apoptosis signaling is starting to emerge. However more studies, notably on the exact function of Cif1p, the role of its cleavage and the other proteins implicated in the Cin state will be necessary to draw the complete scheme of this unprecedented cellular pathway.

Keyphrases: Chaperone, Schizosaccharomyces pombe, Ribosome, Calnexin, Nucleolus, Prion