NCube/papyrus huggingface dataset:
«Tu n’es plus mon ami» : les amitiés Facebook affectées pendant les élections brésiliennes 2014

In 2014, it took place the most contested elections for the position of President of the republic of Brazil since 1989, year of the first direct vote after the return to democracy in the country, following a 21-year military dictatorship. The electoral climate invaded the social network sites, which made the Brazilian presidential election the most commented subject on Facebook in the world that year (Facebook, s.d.).  Researches concerning political interactions on social networks, including Facebook, rarely devote to the consequences that they may have on friendships. Given the findings, the question that emerged was this: did the conversations about the Brazilian presidential election on Facebook affect friendships? The research presented in this paper seeks to explore this issue, to better understand the role of political conversations on Facebook friendships, as well as its impact on the face-to-face interpersonal relationships.  This research was developed on the foundation of the Grounded Theory, a theory that understands itself as an empirical method of data collection and analysis. Grounded Theory assumes that qualitative analyses of data may allow researchers to produce a “theory”, an explanation of located phenomena, able to highlight specific contexts (Guillemette, 2006). To help me align myself with this theory, I interviewed by Skype or FaceTime ten Brazilians. The interviews were focused on the behaviors they adopted towards these "friends" on Facebook and face-to-face.  The results suggest that posts about politics during the election period in 2014, in Brazil, have generally been considered as a risk-taking and could lead the user’s "friends" to unfriend or unfollow him, or change his status. The different types of friendship have also played, in a qualitative point of view, a central role in the management of "friends" on the platform. The results indicate that participants were more tolerant with close friends and those with whom they had a face-to-face relationship. The exclusions have mostly targeted the "acquaintances". Finally, although none of the research participants has broken down an interpersonal relationship on face-to-face, they nonetheless felt influenced and, sometimes, "disappointed" by their friend’s posts. Some participants recognized that some interpersonal relationships have cooled down; others affirmed that they had less interest in some people; and others declared avoid meeting people whose political views, revealed on Facebook, could disappoint them.

Keyphrases: Facebook, unfriending, Friends, social networks sites, social media, political discussion, elections
Recréer et comprendre les mécanismes de liaison des biomolécules à l'aide d'un modèle d'ADN

Molecular recognition plays a central role in almost every biological and biotechnological process.  Over the last 60 years, two molecular recognition mechanisms have been used to appropriately describe the coupling between binding and conformational change in biomolecules.  The induced fit mechanism takes place when ligand binding to the inactive state of the biomolecule induces the conformational change leading to the active state.  On the other hand, in the conformational selection mechanism, where active and inactive states exist in equilibrium, the ligand binds selectively to the active state of the biomolecule and shifts the equilibrium towards this state by stabilizing it.  Even though these mechanisms have been widely studied, it is still unclear if they differ in performance or how each mechanism can be modulated.  Such a fundamental understanding of the differences between these mechanisms would shed light on the reasons for an apparent selective pressure driving the use of a specific mechanism for a given biomolecule and would also allow us to engineer new biomolecules which would benefit from the strengths of these mechanisms.   To date, both mechanisms have been exclusively studied in the context of naturally occurring biomolecules, mainly proteins, whose structural and dynamic complexity as well as diversity seem to prevent comparison and manipulation of specific and individual thermodynamic parameters.  Consequently, only little progress has been made towards characterizing the role of certain key thermodynamic parameters on the selection and performance of the mechanism.  To circumvent this limitation, we have reproduced these mechanisms using simple fluorescent DNA constructs allowing for reliable prediction and variation of both structure and thermodynamics as well as real time monitoring of the activation process in presence of a DNA target.  These DNA "switches" allowed us to determine that an induced fit mechanism occurs when the binding site is partially available in the inactive state and that this mechanism allows for a faster activation and deactivation (up to four orders of magnitude) compared to a conformational selection mechanism, which in contrast corresponds to a slower activation and deactivation, leading to a longer activation period.  The observed kinetic differences between these mechanisms points towards potential uses for both in different areas of biotechnology as well as some rationale behind evolution favoring one mechanism over the other for a given protein.

Keyphrases: Régulation, Induced fit, Conformational selection, Binding mechanism, Conformational change, Regulation, Kinetics, Thermodynamics, DNA switch
Approches globales afin d’élucider les mécanismes pathogéniques de la dystrophie myotonique de type 1

Myotonic dystrophy of type 1 (DM1) is a degenerative disorder implicating symptoms of muscular atrophy and myotony. In a molecular level, it is caused by the aberrant expansion of CUG repeats in the 3’-UTR region of the DMPK mRNA (Dystrophia Myotonica protein kinase). Excessive CUG repeats then form toxic aggregates (foci) enriched within the nucleus of DM1 patient cells. These RNA foci cause the abnormal sequestration of RNA Binding Proteins (RBP), in particular members of the Muscleblind-like protein 1 (MBNL), that normally bind the CUG motif of other target RNAs, and will hence alter their normal functions. In addition to their role in alternative splicing, MBNL1 has recently been implicated in the intracellular localisation of its RNA targets. It remains elusive whether the pathogenesis of DM1 could result from the deregulating effect of CUG repeats on the localisation of specific RNAs and RBP proteins. In this thesis, a fluorescent imaging-based screening of 322 RBPs in DM1 patient’s myoblasts has been conducted and this had led to the identification of new factors that may colocalize with pathogenic CUG expansions. Moreover, these DM1 myoblasts have been fractionated and subsequent RNA-sequencing has permitted the identification of transcripts that are delocalised between subcellular compartments. From the two large datasets generated from the RBP imaging-based screening and fractionation/RNA-sequencing, new avenues of research can be initiated to further understand not only DM1, but perhaps also other disorders that implicate microsatellite expansions.

Keyphrases: DM1, MBNL, RBP, Foci, FISH-IF, Myotonic dystrophy type 1, RNA localization, Cell fractionation, RNA-sequencing
Caractérisation du microDNome et sa modulation par le traitement anti-cancer

Recently, a new class of extrachromosomal circular DNA (eccDNA) called microDNA was identified in mouse and human tissues. These microDNAs are 100 to 400 bp long, derive from unique nonrepetitive genomic regions and show an enrichment in GC rich and genic sequences. While it has been proposed that they could arise from RNA metabolism or replication defects, their production mechanisms and eventual functionality remain unclear. Through the analysis of microDNAs extracted from a series of 10 human lymphoblastoid cell lines (LCLs), we confirmed the non-random distribution of microDNA towards active regions of the genome. Identified microDNAs showed redundant loci of origin and a size periodicity of 190 bp that matched caspase-dependant DNA fragmentation of apoptotic cells. Strikingly, the chemotherapeutic drug-induced apoptosis (using methotrexate or Lasparaginase) of these LCLs modulated both diversity and size of microDNAs further suggesting that a part of microDNAs could represent circularized by-products of the programmed cell death. Thus, while compatible with the original observation that microDNAs originated from a normal physiological process, these results imply an alternative or complementary source of production.

Keyphrases: MicroDNA, Extra-chromosomal circular DNA, Next-Generation Sequencing, Apoptosis
A la racine du jihad : une analyse linguistique

This research is an attempt to unveil a channel for interreligious and intercultural dialogue by using the jihad as common ground for discussion using a perspective inspired by Freudian and Lacanian psychoanalysis which discusses the relation between the subject-researcher and the object of research. Thus, this scientific endeavour tries to disengage an understanding of jihad that would be subverted by a colonial legacy identified by Edward Said as “orientalism”, legacy that circumscribes the object jihad in “whatever is allowed it to be”. This leads the research to question the ontological status of the object jihad, and shifts this status from concept to signifier due to the linguistic nature of this work. Signifier which is conceptualised by a “retour à la lettre” from which emerges a long forgotten “Arabic signifier” constructed from the trilateral root JHD and the development of a new conceptual tool: the “semantic cloud”. This signifier is hence inserted in its natural environment which is defined as the Qur’an in the Arabic language and is analysed to test the hypothesis: There is in the Arabic Qur’an a signifier constructed from the root JHD determined by the definite article al- which takes the form “al-jihād”.

Keyphrases: Jihad, Islam, Orientalism, Linguistic, Psychoanalysis, Qur'an, Semantic cloud, Arabic, Grammar
Les croyances paranormales au Québec : des bricolages religieux dans un contexte de tradition catholique

This research project deals with beliefs about paranormal activity in the province of Quebec. Drawing on fieldwork conducted from 2014 to 2015 in the Laurentians, the project provides a picture of paranormal beliefs, spiritualism and believers. Contextualizing the steps taken by participants to integrate, as part of their local Catholic heritage, their beliefs about the paranormal, and interpreting these using the concepts of religious bricolage, phenomenology and belief, it was possible to create a profile of a typical believer in the paranormal and the context in which such beliefs can appear and evolve. Most of the participants in this project had had a paranormal experience that they interpreted in the light of the death of a person, and then had their analysis validated by a medium with a Gift, that according to them involved the ability to communicate with “the beyond”. The belief in the continuity of the human soul after the death of the body seems to be a pillar of beliefs in the paranormal. Participants, who had all experienced inexplicable phenomena, also tended to fear the judgment of others and so avoided talking about their beliefs. This fact contributes to the misunderstanding of paranormal beliefs and it is at this stage that the medium plays the role of intermediary between the participant and the phenomenon, by authenticating the event as real. This thesis analyses the process of legitimation of beliefs in the paranormal and the existence of mediumship in a post-Quiet Revolution context in Quebec, where reason and science may still be insufficient for providing all the answers that people seek.

Keyphrases: Paranormal, Possession, Paranormal activity, Paranormal beliefs, Spiritualism, Believers, Catholic heritage, Religious bricolage, Phenomenology, Belief, Medium
Une correction à l’échelle et progressive des données Hi-C révèlent des principes fondamentaux de l’organisation tridimensionnelle et fonctionnelle du génome

Over the last decade, accumulating empirical evidence suggest that, as much as its sequence, a genome spatiotemporal organization is essential to understand it’s biological function. One of the major breakthroughs has been chromosome conformation capture (3C) experiments presenting DNA-DNA contact for whole genomes at unprecedented resolution (5-10kb). Along with genome-wide maps of DNA contacts came genome 3D modelling from experimental 3C data, and even from purely theoretical and biophysical basis. However, the mechanisms underlying the regulation of the genome spatial functional organization are still not well understood. Among other questions, how the regulation and event of nuclear processes such as transcription modulate genome structure or how genome structure affect these in turn is still not fully resolved. Moreover, computational models of S.cerevisae genome have recapitulated the hallmarks at larger scale of its 3D features. In order to contrast genome structural features arising from the event of biochemical and molecular activity, we have develop a method assessing the significance of structural features. The underlying principle is to consider for a given interaction, the two DNA regions put in contact and the distribution of existing interactions between these before assigning significance to the selected interaction. Using this method, we demonstrate that structural features resulting from potential biochemically active processes occur at precise scale on the genome. Our results also highlight that exact nature of the interaction (between vs across chromosomes) is crucial to such events. Finally, we have also found that a large portion of transcription factors have their targeted genes in spatial proximity.

Keyphrases: Données de type 3C (Hi-C), Genome spatial (3D) structure, Genome functional organization, Transcriptional regulation, Chromosome conformation capture (3C), 3C data correction
Synthèse efficace d'hétérocycles azotés par activation d'amides engendrée par l'anhydride trifluorométhanesulfonique

Nitrogen-containing heterocycles are of considerable importance in the pharmaceutical area. These types of compounds are indeed found in numerous bioactive structures patented in the last few years. Although these motives are useful, their synthesis often necessitates multiple steps or the use of highly functionalized starting materials. The present thesis describes new methodologies to access these synthetically challenging structures in a mild, chemoselective and step-economic fashion by amide activation using trifluoromethanesulfonic anhydride. First, a two-step method to access 3-aminoindazoles from the corresponding aromatic amide has been developed. The sequence includes a one-pot trifluoromethanesulfonic anhydride-mediated amide activation to form the corresponding iminium trifluoromethanesulfonate, followed by the addition of a protected hydrazide to access the amino hydrazone intermediate. This intermediate can then undergo cyclization through a palladium-catalyzed C-H amination reaction to afford the desired 3-aminoindazole. Various 3-aminoindazoles could be obtained in moderate to good yields.  Moreover, a new methodology for the synthesis of 3-amino imidazo[1,2-a]pyridines was developed. 2-Aminopyridine-containing amides were treated with trifluoromethanesulfonic anhydride to afford the desired heterocycles in good to excellent yields. The products thus obtained could then be further functionalized using ruthenium and palladium catalyzed C-H arylation reactions.

Keyphrases: amides, 3-aminoindazoles, activation C-H, Heterocycles, Trifluoromethanesulfonic, Anhydride, C-H activation
Modélisation de la formation des aérosols organiques secondaires dans les régions polluées

Atmospheric aerosols (i.e. particulate matter or PM) are a major source of uncertainty in climate models. Many studies have also shown that elevated concentrations of PM reduce life expectancies. Secondary organic aerosol (SOA) is formed in the atmosphere from gaseous precursors through chemical reactions and SOA represents a major component of PM mass globally. To better understand the chemical pathways responsible for SOA formation, a box model is designed to simulate dynamically the evolution of organic species in an air parcel as it undergoes photochemical oxidation producing SOA. The model incorporates recently published parameterizations for the formation of SOA from volatile organic compounds (VOCs), as well as from semi-volatile and intermediate-volatility organic compounds (SVOCs and IVOCs). The model is constrained by several measurements of precursors, including recently developed measurements that provide greatly improved constraints on precursor concentrations, and the predications are compared against measurements of SOA taken during the CalNex campaign. When accounting for the effect of chamber wall-losses on VOC yields, the amount and rate of SOA formation in the model is more consistent with observations. The results of this study also indicate that the primary SVOCs and IVOCs are responsible for a majority (70 – 86 %) of the model SOA mass, emphasizing their high contribution as SOA precursors. However, the SOA mass predicted is underestimated at shorter photochemical ages when compared to field measurements, but at longer ages, model/measurement agreement is observed. This bias may be due to low IVOC/CO emissions ratios or low estimated IVOC oxidation rate constants, which highlights the need for further field and laboratory studies of these compounds.

Keyphrases: Model, Air Quality, SOA yields, Volatility, Photochemical Oxidation, PM 2.5, VOCs, IVOCs, SVOCs, SOA
Impact de l’âge sur le métabolisme de la kétamine et du midazolam chez le rat en utilisant des fractions S9 et la spectrométrie de masse

Ketamine is a NMDAR antagonist widely used for anesthetic procedures and less often to treat chronic pain. Work in our laboratory showed that the use of ketamine combined to xylazine is a poor anesthetic choice for aged rats of approximately 2 years. Considering that geriatric patients present physiological characteristics demanding adaptations of the pharmacotherapy, that this class of patients frequently needs anesthesia to perform surgeries and that they represent the subpopulation that uses many drugs to treat acute and chronic pain, it is relevant to investigate the impact of aging on drug metabolism. The goal of this project was to assess the impact of aging on ketamine metabolism using cellular fractions (in vitro) and liquid chromatography tandem mass spectrometry. First, we needed to confirm the main metabolic pathway of norketamine formation using well-established reference substrate and inhibitor of CYP3A metabolic pathway which are respectively midazolam and ketoconazole. Furthermore, we also characterized the metabolic interaction of ketamine frequently combined with midazolam. Second, we compared the degradation profiles of ketamine in liver S9 fractions of rats aged of 3, 6, 12 and 18 months. Vmax values (±SD) were respectively of 2.39 (±0.23), 2.61 (±0.18), 2.07 (±0.07) for the younger groups compared to 0.68 (±0.02) for the 18 month older group (p < 0.001). Those results suggest that CYP3A is quickly saturated by the presence of ketamine. Moreover, Km value showed a 6 to 7 fold decrease for the oldest group compared to the younger one (p < 0.05). Therefore, we hypothesized that the enzyme undergoes conformational changes, which results in a decrease of norketamine formation. Finally, we intend to assess the contribution of brain metabolism to the overall ketamine metabolism. Unfortunately, we did not find any significative difference in ketamine or midazolam concentrations between the beginning of the reaction and 60 minutes later. The same ascertainment has been observed with other susbstrates of CYP3A and CYP2D (dextromethorphan and codeine). Other experiences are needed to definetely conlude that brain metabolism is negligible. The differences observed between age groups suggest that the hepatic metabolic pathway of CYP3A is severely impaired. Anesthetic protocols for aging patients should take into consideration the diminished metabolic activity since it may lead to a significant increase of exposition to systemic drug concentrations.

Keyphrases: midazolam, CYP3A, interactions médicamenteuses, ketamine, midazolam, aging, CYP3A, drug metabolism, drug-drug interactions, mass spectrometry
A systematic in vitro metabolism study of opioids using rat liver S9 fractions and mass spectrometry revealed CYP2D metabolism is impaired with age

Codeine and oxycodone are opioids used in the treatment of pain. The outcome of the treatment is ultimately related to their metabolism by CYP450 enzymes. Depending on the drugs used, alterations in the metabolism of drugs by CYP450 enzymes can lead to severe conséquences including alterations in their efficacy, safety and toxicity profiles. The objective of this study was to assess the effect of age on CYP2D enzyme metabolism in rats using HPLC-MS/MS (Linear Ion Trap). Codeine and oxycodone along with specific metabolites morphine (CYP2D), norcodeine (CYP3A), and oxymorphone (CYP2D), noroxycodone (CYP3A) were quantified using isotopic dilution method. Liver S9 fractions from 3, 6, 12, and 18 month-old male Sprague Dawley rats were prepared and Michaelis-Menten parameters were determined for their primary metabolic pathways. The derived maximum enzyme velocity (Vmax) suggested a rapid saturation of the CYP2D active sites in the liver S9 fractions of 18 month-old rats. The observed Vmax values for codeine in 3, 6 and 12 month-old rats respectively were 0.327 ± 0.027, 0.355 ± 0.021 and 0.273 ± 0.028 and for oxycodone, the values were 0.690 ± 0.096, 0.499 ± 0.087, 0.153 ± 0.01. For 18 month-old rats, Vmax value was 0.092 ± 0.003 for codeine compared to 0.153 ± 0.01 for oxycodone. The Vmax value affected significantly (P ≤ 0.05) the enzyme-mediated clearance of these drugs (CLuint = Vmax / Km). The results of this study suggest that CYP2D enzyme undergoes a conformational change with age, particularly in 18 month-old rats considered to be geriatric in age, thus leading to a significant decrease in the rate of the formation of active opioid metabolites and a decrease in enzymatic clearance of these drugs. This study suggests that there is an impairment of CYP2D and CYP3A in aging rats, which affects their drug metabolism.

Keyphrases: CYP450, CYP2D, CYP3A, Opioids, Aging, Drug metabolism, Mass spectrometry
Dégradation du collagène dans le cartilage équin par la cathepsine K

Type II collagen, which gives the cartilage its tensile strength, is destroyed in osteoarthritis (OA). Cathepsin K is recognized as capable of cleaving type II collagen, however, the regulation of its activity in the cartilage is little known. Our hypothesis is that the activity of cathepsin K in cartilage is measured by an ELISA specific to cathepsin K cleavage site. A new specific ELISA (C2K77) was developed and tested by measuring the activity of the exogenous cathepsin K. The ELISA C2K77 was then used to measure the activity of the endogenous cathepsin K in equine articular cartilage explants cultured with or without stimulation (IL-1β, TNF-α, Oncostatin M (OSM) and LPS). Then the activity of cathepsin K was compared to that of MMPs (C1,2C ELISA) in the cartilage explants and in the freshly harvested cartilage. A significant difference was observed between normal cartilage and cartilage digested with cathepsin K (p˂0.01). There was no significant difference in the content of C2K77 between the control group and the groups stimulated while the content of C1,2C was increased by the combination of IL-1β and OSM (p = 0.002) and TNF-α and OSM (p˂0.0001). The new ELISA C2K77 demonstrates the ability to measure the activity of cathepsin K and revealed that there is a difference between the regulation of cathepsin K and MMP in articular cartilage.

Keyphrases: MMPs, ELISA, OA, cartilage, cytokines, cathepsin K, type II collagen, Osteoarthritis, equine