NCube/papyrus huggingface dataset:
Purification par affinité et marquage isotopique spécifique pour études d’ARN fonctionnels

The tridimensional structure of a given RNA molecule is closely linked to its cellular function. For this reason, it is crucial to study the structure of RNA molecules, such as riboswitches, to characterize their mechanism of action. To do so, NMR spectroscopy is often used to gather structural data on RNA molecules in solution. However, this approach is limited by two main difficulties. First, the production of preparative quantities of natively folded and purified RNA molecules is a long and tedious process. To facilitate this step, our laboratory has developed an RNA-affinity purification method using an ARiBo tag. The second limiting step comes from the extensive signal overlap detected on NMR spectra of large RNA molecules. This overlap is proportional to the length of the RNA, which often prevents high-resolution structure determination of RNAs larger than 15 kDa. To solve this problem, specific isotopic labeling of RNAs can now be achieved. However, existing labeling protocols are expensive, require several weeks of laboratory manipulations and usually provide relatively low yields.                                                  This thesis provides an alternative strategy to achieve specific isotopic labeling of RNA molecules, based on the ARiBo tag affinity purification technique. The protocol includes the separation and the purification of isotopically labeled nucleotides, an enzymatic ligation step performed on a solid support and the affinity purification of the RNA of interest, without any sequence restriction. This new strategy is a fast and efficient way to label functional RNAs isotopically and should facilitate NMR structure determination of large RNAs.

Keyphrases: Ribonucléoside monophosphate (NMP), Ribonucleoside monophosphate (NMP), NMP separation, RNA, Affinity purification, Isotopic-labeling, Nuclear magnetic resonance (NMR)
Synthèse totale de la pactamycine et d’une sélection d’analogues, progrès vers la synthèse totale de la daphniglaucine C et brève étude d’une transposition allylique réductrice

Although pactamycin was first isolated as a potential antitumoral drug, further studies highlighted its capacities in inhibiting protein synthesis, and thus its potency as an antibacterial agent. Furthermore, it was recently discovered that some of its analogs display promising antiprotozoal activity. The present thesis reports and details the first total synthesis of pactamycin, pursued in the Hanessian lab over the last few years, as well as the preparation of a selection of analogs thereby tested for their biological properties.  Daphniglaucin C belongs to a large family of natural compounds isolated from the leaves of daphniphyllum over the last decade. Although relatively little is known as to the biological activity of daphniglaucin C, its synthesis poses an obvious and interesting challenge for organic chemists. En route towards its total synthesis, the use of several methods for the formation of quaternary centers was explored. Moreover, an atypical reductive allylic transposition, catalyzed by palladium from unactivated allylic alcohols, was studied and used to generate a variety of polysubstituted pyrrolidines.

Keyphrases: Pactamycin, daphniglaucin C, polysubstituted pyrrolidines, alkaloids, total and diastereoselective synthesis, sigmatropic rearrangements, quaternary centers, antibiotic, anticarcinogenic and antiprotozoal, allylic alcohols
Influence de la taille de départ, de l’état d’agglomération et de la dose de nanoparticules de dioxyde de titane (TiO2) inhalées sur la réponse pulmonaire chez le rat

Given their small size, nanoparticles (NP) (< 100 nm) can coagulate quickly, which promotes their entry into the body in the form of agglomerates. The objective of this study is to evaluate the influence of the agglomeration state of three different primary particle sizes (5, 10-30 and 50 nm) of titanium dioxide (TiO2) NP on the pulmonary toxicity of male rats (F344) exposed to aerosols at 2, 7 or 20 mg/m3 for 6 hours.  In an inhalation chamber, six groups of rats (n = 6 per group) were acutely exposed by nose-only inhalation to aerosols with a 5-nm primary particle size, produced in the form of small agglomerates (< 100 nm) (SA) or large agglomerates (> 100 nm) (LA) at 2, 7 and 20 mg/m3. Similarly, four other groups of rats were exposed to aerosols at 20 mg/m3 with a primary particle size of 10-30 and 50 nm. The different aerosols were generated by nebulization of suspensions or by dry dispersion. For each mass concentration, one group of control rats (n = 6 per group) was exposed to compressed air under the same conditions. The animals were sacrificed 16 hours after the end of exposure, and analysis of the bronchoalveolar lavage fluids was used to measure markers of inflammatory, cytotoxicity and oxidative stress effects. Lung sections were also analyzed for histopathology.  The influence of the agglomeration state of TiO2 NP (5 nm) could not be determined at 2 mg/m3. For mass concentrations of 7 and 20 mg/m3, our results showed that an acute inflammatory response was induced following exposure to LA aerosols. In addition to this response, exposure to SA aerosols resulted in a significant increase in 8-isoprostane and lactate dehydrogenase. At 20 mg/m3, the cytotoxic effects were greater after exposure to the 5-nm NP in the SA aerosol. This study showed that TiO2 NP use different mechanisms to induce their pulmonary toxicity as a function of their primary particle size and their agglomeration state.

Keyphrases: Inhalation, Inflammation, Nanoparticles, Titanium dioxide (TiO2), Inhalation, Primary particle size, Agglomeration state, Pulmonary toxicity, Oxidative stress, Cytotoxicity
Étude du rôle de la protéine Vpr du VIH-1 dans la modulation de la réponse immunitaire

Chronic immune activation and gradual depletion of CD4+ T cells are hallmarks of HIV-1 infection, which are thought to contribute to the progressive deterioration of the host’s immune response that ultimately leads to AIDS. Paradoxically, the majority of CD4+ T cells that are destroyed are uninfected and causes for this bystander effect of infection on CD4+ T cells remains unclear. Some HIV-1 proteins, including the accessory protein Vpr, are suspected to play a role in this process. Vpr, expressed late during HIV-1 infection, is shown to be incorporated within the budding virions as well as secreted as soluble protein in the extracellular medium from the infected cells. The main biological function of Vpr is the induction of a G2/M cell-cycle arrest through the recruitment of the E3 ubiquitin ligase complex DDB1-CUL4AVprBP and activation of the ATR-mediated DNA damage pathway. One study showed that activation of DNA damage pathways leads to the expression of specific ligands for the activating receptor NKG2D expressed on NK cells, thus triggering NK cell cytolytic function. Interestingly, several evidences suggest that HIV-1 upregulates expression of specific NKG2D ligands on infected CD4+ T cells. However, the viral factor involved in this process remains undefined. The aim of this thesis was to evaluate the role of Vpr in modulating NK cell cytolytic function and its potential involvement in CD4+ T cells depletion. Our work demonstrated that the expression of Vpr, alone or in the context of HIV-1 infection, is sufficient to specifically increase expression of the NKG2D ligand, ULBP2, on primary CD4+ T cells. Consequently, these CD4 T cells become more susceptible to autologuous NK cell-mediated lysis. Our studies have shown that this Vpr-mediated ULBP2 upregulation requires the recruitment of the E3 ubiquitin ligase complex DDB1-CUL4AVprBP and the activation of the ATR-mediated DNA damage pathway. More importantly, we provide evidence that Vpr augments ULBP2 expression on both infected and uninfected bystander cells during HIV-1 infection of primary CD4+ T lymphocytes. In that context, we show that delivery of Vpr into uninfected cells via defective viral particles is sufficient to upregulate ULBP2 and increase their susceptibility to autologuous NK cell-mediated killing. In addition, we describe for the first time that soluble Vpr has the ability to induce DNA damages and upregulate ULBP2 upon transducing target cells, including T cells. Overall, our results show that Vpr is a key HIV-1 factor involved in the upregulation of NKG2D ligands induced by HIV-1. This upregulation of UBP2 might contribute to depletion of infected and uninfected CD4 + T cells through activation of NK cell cytolytic functions. A better understanding of the contribution of this new activity of Vpr in HIV-1 pathogenesis has the potential to enable the development of new therapeutic targets or therapeutic strategies against HIV-1.

Keyphrases: Virus, Vpr, ATR, ULBP2, NKG2D, HIV-1, Accessory proteins, NK cells, CD4+ T cells depletion
Étude de l’appropriation de l’orthographe française langue seconde/étrangère d’élèves arabophones du secondaire en Égypte

The aim of this research was to assess French language-spelling development for the first year Arabic language-speaking students of the Secondary Schools in Egypt. These students were studying “French” as a foreign language. Previous studies performed in Egypt addressed the grammatical errors committed by these students in the field of “written French language”. To date, and to the best of our knowledge, there are no available studies addressing the issue of “French language-spelling development”. To fill this gab in literature, we examined the spelling competence of the students. We evaluated the features of the French language - spelling development for the first year Arabic language - speaking students in Secondary schools in Egypt. Also, we examined the relationships between these features and corresponding features in French and Arabic language development for preschool Arabic language-speaking children in Quebec.    To achieve our goals, 30 students of the first year Arabic language-speaking students in Secondary schools in Egypt underwent a test of invented spelling, through semi-structured interview. The test was repeated four times on different occasions. During the test, the students were asked (on individual basis) to produce some writings (French language). The results of these tests raised three writing features, namely: visuographic, phonological and orthographic concerns. Moreover, their writings showed a language transfer produced from both Arabic as a mother language and English as a foreign language. Our findings revealed that, during writing, students have employed three strategies: lexical, phonological and orthographic.   In addition, a multiple case study exploratory was conducted with four Arabic language-speaking preschool children in Quebec. Each child was asked to produce some writings in French and in Arabic languages. The French language-spelling development of the students the Secondary Schools was made comparable to that of the preschool children in French. Such strategy allowed us to test the effect of age on the spelling development and on language transfer. We found that the written performance of the students from Secondary Schools was significantly more advanced as compared to that of the preschool children. Also the students from Secondary Schools were more able to produce language transfer. These findings indicated that the learner’s age had a significant impact not only on the French language - spelling development but also on the language transfer in second/foreign language. Finally, the scientific and practical ramifications open avenues for further investigations in these fields.

Keyphrases: spelling appropriation, invented spelling, mother language, foreign language, second language, Arabic language-speaking students in Secondary Schools and in preschool, language transfer, learner’s age
Indirect Bonding Method: in vitro Comparison of the Shear Bond Strength between Metallic Orthodontic Brackets and Different Porcelain Surface Preparations

Background : Bond strength at the metal-ceramic interface of auto-polymerizing resins used in orthodontic indirect bonding has not yet been evaluated and a literature-based clinical protocol is lacking.  Goals : 1) To compare shear bond strength (SBS) between metal brackets and differently treated porcelain surfaces; 2) To suggest efficient and predictable chairside approaches. Materials and methods : Ninety leucite discs (6 groups; n=15/group) were prepared following 6 combinations of mechanical (+/- bur roughening) and chemical (hydrofluoric acid, primer, silane) treatments. Metal brackets with custom composite resin Transbond XT (3M Unitek, Monrovia, California) bases were bonded with the adhesive resin system Sondhi A+B Rapid Set (3M Unitek, Monrovia, California). Samples were stored (H2O/24hrs), thermocycled (500 cycles) and tested (Instron, Norwood, Massachusetts). Maximum SBS and adhesive remnant index (ARI) scores were collected for each sample. ANOVAs were performed on ranks since data was not normally distributed, and then adjusted with the post-hoc Tukey method. A Kruskall-Wallis, a Mann Whitney U pairwise comparison and a Weibull analysis were also performed.  Results : SBS medians of groups ranged from 17.0 MPa (- bur + hydrofluoric acid) to 26.7MPa (- bur + hydrofluoric acid + silane). Bur roughening did not affect bond strength. The chemical preparation of (- bur + primer + silane) showed statistically significant higher SBS than (- bur + hydrofluoric acid) preparation (p<0,05), while having similar SBS to the popular recommended protocol (- bur + hydrofluoric acid + silane). ARI scores were statistically significant lower in group (- bur + hydrofluoric acid) with p<0,05, while all other 5 groups were not different from each other. Percentage of porcelain damage in these 5 groups were very high at 80-100%. Conclusion : All the tested surface preparations combinations provided clinically adequate adhesion for orthodontic tooth movement. A silane and primer combination for porcelain surface preparation is clinically attractive as it is safe and simple and provides great adhesion for orthodontic tooth movement. It is wise to warn patients that there is a risk of porcelain fractures when debonding brackets. If one prefers to avoid porcelain fracture at all cost, one may treat porcelain with hydrofluoric acid only.

Keyphrases: Sondhi, Porcelain, Ceramic, Surface preparation, Indirect bonding, Metal bracket, Orthodontic
Effet de l’expansion palatine sur le bruxisme du sommeil chez des enfants en comparant des appareils d’expansion palatine rapide collé ou bagué

Introduction: Sleep bruxism (SB) is a movement disorder described as an involuntary mastication movement during sleep. This parafunction is observed in 14-38% of the child population. A link was found between respiratory events and episodes of bruxism. Rapid palatal expansion (RPE) in children is an orthopedic treatment that is effective in correcting maxillary transverse deficiency and in reducing obstructive apnea syndrome (OAS) by increasing airway capacity. Objectives : Since bruxism is related to respiratory events and RPE increases respiratory capacity, the objective of this study is to evaluate the possible reduction of bruxism after RPE therapy. Material and Methods : This prospective randomized controlled clinical pilot study recruited 27 children (8-14 years old, 8 boys, 19 girls) with or without sleep bruxism. These patients were seeking treatment for transverse maxillary deficiency (5 mm or more) at the orthodontics department of the University of Montreal. Patients underwent an ambulatory polysomnography before (T0) and after expansion (T1). Sleep parameters, rhythmic muscular masticatory activity index were evaluated. Results : The results show a reduction of bruxism in 60% of bruxer patients (9 participants). The interaction between the treatment and the groups (Br and ctl) was significant (p=0,05, repeated measures ANOVA). A reduction of bruxism is shown for bruxers (p=0,04, paired t-test). The sleep parameters stayed stable after RPE (Stage N1/N2/N3, REM, sleep efficiency) as well as the breathing parameters and snoring data. The medians (min, max) of bruxism group went from 3,11 (2,06; 7,68) to 2,85 (0,00; 9,51). Conclusion : During this study, a reduction of bruxism was observed but a larger sample size is needed to conclude on the subject.

Keyphrases: rapid palatal expansion, sleep bruxism, children, polysomnography, maxillary transverse deficiency
Les tiers dans le contentieux arbitral des investissements internationaux : de l'intervention au recours direct

International arbitration has remained an exclusive domain sovereign states until, in the late 50s, came the first bilateral investment treaties (BITs). The main feature of these BITs is undoubtedly the right, granted to investors, to direct international arbitration against recalcitrant States, an alternative to often ineffective local justice. More recently, in 1998, the appellate body of the WTO went to accept the opinion of an independent amicus curiae in a dispute between State members. Today, the admission of such opinions is clearly provided for in several recent BITs. But if investors benefit from a right of action before a neutral international arbitration body, the situation is quite different for the local population, who is often affected by the presence of foreign investors on its territory. The right to submit an opinion cannot replace the right to legal action. This therefore raises one question: in the current context of international investment law, is it possible for third parties (non signatories of BITs and not parties to the dispute) are entitled to a remedy direct international arbitration? We are of the opinion that the answer to this question is: yes. And the context of investment arbitration, because of the right to direct arbitration against States already granted to investors, constitutes a fertile ground for the implementation of this right of action in favour of third parties. The objection based on the absence of the parties’ consent to such right of action has been set aside in many international arbitration cases where the scope of consent has been extended to include non-parties or to submit to arbitration matters not contemplated at first. Also, the objection based on the absence of legal standing of third parties in International Law proves to be theoretical as foreign investors already have access to international justice despite the lack of this quality. There remains to determine what substantial International Law will constitute a valid legal basis for a third party claim. We will see that there exists legal instruments and international principles and that their violation by States or investors may result in the obligation to compensate the prejudice suffered, as well as it is possible to clearly define and indentify who the third parties could be.

Keyphrases: Amicus curiae, International arbitration, Investment arbitration, Civil society, Foreign investment, International investment, Amicus curiae, Dispute settlement, Dispute settlement procedure, Third party claim
Évaluation d’un programme de triage des références en rhumatologie pour la prise en charge rapide de la polyarthrite rhumatoïde

Background : In patients with early rheumatoid arthritis (ERA), use of disease-modifying anti-rheumatic drugs substantially improves patient outcomes. Patients treated by rheumatologists are more likely to receive these treatments and to have better disease outcomes. However, delays from symptoms onset to first rheumatologist visit often exceed the guideline recommendations of 3 months. Waiting time to see a rheumatologist after a referral is made, is generally long in Quebec and contributes to those delays. Objectives : We evaluated the ability of a nurse-led triage and rapid access program to identify patients with ERA and reduce their waiting time, in order to improve process of care.  Methods : A nurse assessed all new referrals received between 2009 and 2010, in a suburban Montreal rheumatology clinic. Priority level was assigned based on the written content of the referral, a telephone interview with the patient and, if needed, an partial joint examination. Patients with ERA, including undifferentiated inflammatory arthritis, and other acute rheumatologic conditions were prioritized and given an appointment as early as possible. The main outcome measures were validity (sensibility and specificity) of the priority level for patients with ERA and delay from referral to first visit with rheumatologist. Results : Of 701 newly referred patients, 65 had a final diagnosis of ERA. The triage correctly identified 85.9% of patients with ERA and 87.2% of patients with other high priority conditions. The median delay between referral date and first visit was 22 days for patients with ERA and 115 days for all others.  Discussion and implications : This nurse led triage and rapid access program correctly identified most patients with ERA and resulted in rapid consultation for these patients. Since this is a labor intensive program, feasibility issues need to be resolved before implementing this type of triage in a resource constrained healthcare system.

Keyphrases: triage, rheumatoid arthritis, early arthritis, rheumatology, triage, prioritization, wait time, program evaluation
Étude des stratégies employées par des parents d’enfants
d’âge préscolaire pour favoriser la saine alimentation et
le repas en famille agréable

Context. Food attitudes and behaviors developed during early childhood greatly influence the future relationships that children will have with food. Parents play a major role in this part of their preschool child’s life. Objective The main goal of this study is to explore attitudes and behaviors that Quebec parents adopt at meal time with their preschooler in order to encourage healthy eating practices as well as enjoyable family meals. Methodology. To collect data, postcards, an innovative tool, were sent to six hundred fifty day-care centres, also known as Centres de la petite enfance (CPE), of which there are more than a thousand in Quebec. The postcards were then distributed to parents, who were asked to respond to two open-ended questions. Analysis of the qualitative data was based on Jean-Pierre Poulain’s food intake model. Results. More than a thousand (1,257) postcards were used in the analysis. Data collected illustrate first and foremost the vision that parents have of healthy eating and reveal two diametrically opposed perspectives: quality and quantity. With regard to family meals, respondents frequently mentioned conversation at the table, the presence of all family members and the absence of television while eating. Conclusion. Findings from this study show the diverse strategies used by Quebecers during mealtimes. The data are essential to defining key public health messages about eating habits for children that should be promoted among these influential actors.

Keyphrases: Attitudes, Parents, Feeding practices, Attitudes, Parents, Preschool age child, Preschooler, Family meals, Food behaviors