NCube/papyrus huggingface dataset:
New insights into small molecules inhibitors and protein-protein interactions of VirB8 : a critical conserved component of the type IV secretion system

Bacterial Type IV secretion systems (T4SSs) are complexes that are constituted of 8 to 12 conserved proteins and used by many Gram-negative bacteria for the translocation of proteins and DNA-protein complexes as well as for the transport of DNA-protein complexes across their cell envelope. T4SS are excellent model targets for the development of antivirulence drugs as they are essential virulence factor for many bacterial pathogens, such as Brucella suis. Antivirulence drugs that deprive the pathogen of its essential virulence factor, the T4SS, would constitute alternatives to or enhancements of current antibiotic treatment. VirB8, a conserved  core assembly factor in T4SS, forms homo- and heterodimers that are very important for T4SS function in these pathogens. Due to its multiple interactions, we hypothesized that VirB8 is an excellent model for the analysis of assembly factors but also a potential target for drugs that could target its protein–protein interactions, which would disarm bacteria by depriving them of their essential virulence functions. The existence of a monomer-dimer equilibrium and self-association of VirB8 were previously demonstrated as being essential for T4SS biological activity. Guided by quantitative interaction assays, we here identified (i) potential interaction sites with other T4SS components and (ii) isolated small molecules inhibitors as probes for protein function. To further determine the residues important for heterodimerization of VirB8 with VirB10, we conducted alanine-scanning mutagenesis, phage display and in silico docking. These experiments demonstrated that residues located on the β sheet R160, S162, T164 and I165. are involved in the association of VirB8 and VirB10 and mutagenesis of these residues led to a decrease in the heterodimer formation. The general objective of our research is to gain quantitative insights into the role VirB8 plays in T4SS assembly. Based on a structure-inspired high-throughput screening approach, we identified a promising compound BAR-068 that inhibits VirB8 interactions in the nM range. We used spectroscopy by fluorescence, a bacterial two-hybrid assay, chemical cross-linking and crystallography in order to decipher the mechanism of interactions of this inhibitor with VirB8. Ultimately, this may lead to advance the understanding of T4SS inhibition. Our ultimate objective is to characterize the sequence of events between VirB8 and other VirB factors that guides T4SS complex assembly and function. Our research will reveal general principles of membrane protein complex assembly that will enhance our knowledge of a number of different areas including bacterial protein secretion. In addition, this research will inform an innovative strategy for the development of novel antimicrobial drugs.

Keyphrases: virulence, Bacterial infections, secretion systems, pathogens, Gram-negative bacteria, virulence factors, antivirulence drugs, protein-protein interactions
Identification de caractéristiques communes et rares dans les ARN structurés dans la base de données Rfam

Noncoding RNAs (ncRNAs) are RNA transcripts that are not translated into proteins yet they play important functional roles in the cell including gene regulation, transcription and translation. Among the many categories of ncRNAs that were discovered, we find the well-known ribosomal RNA (rRNA), transfer RNA (tRNA), snoRNA and microRNAs (miRNA). The functions of ncRNAs are tightly linked to their structural features. Thus, understanding and predicting RNA structure as well as developing methods to search for new ncRNAs help to gain insight into these molecules. Technological advances have made available abundant sequence information accessible in databases such as Rfam, which provides alignments and structural information of many ncRNA families. In this research project, we retrieved the information from the Rfam database about the sequences of all secondary structures such as hairpin loops, internal loops, bulges, etc. in all RNA families. A local database, RNAstem, was created to facilitate the use and manipulation of information about secondary structure motifs. We analyzed hairpin loops, bulges and internal loops using the compiled data about the frequencies of occurrence of each loop or bulge and calculated a frequency score. The frequency score is aimed to be an indicator for the abundance of a specific secondary structure motif. While minimizing the bias caused by the high redundancy of some RNA classes as ribosomal RNAs, the frequency score allowed us to identify the rare motifs in each category as well as the common ones. Our findings about the abundant motifs confirm what is already known from previous studies (ex. abundant GNRA or UNCG tetraloops). We found very large gaps between the most abundant and rare RNA structural features. Moreover, we discovered that "A" and "U" dominate single stranded RNA regions, whether they are bulges or loops. We further explored the possibility of using this data to improve current prediction tools for ncRNAs by applying a filter to new candidates. We developed a score system, RNAscore, that evaluates RNAs depending on their motif contents and we tested the program with many different controls.

Keyphrases: Rfam, motifs, ncRNA, RNA structure, Secondary structure
Semiautomated 3D liver segmentation using computed tomography and magnetic resonance imaging

The liver is a vital abdominal organ known for its remarkable regenerative capacity and fundamental role in organism viability. Assessment of liver volume is an important tool which physicians use as a biomarker of disease severity. Liver volumetry is clinically indicated prior to major hepatectomy, portal vein embolization and transplantation. The most popular method to determine liver volume from computed tomography (CT) and magnetic resonance imaging (MRI) examinations involves contouring the liver on consecutive imaging slices, a process called “segmentation”. Segmentation can be performed either manually or in an automated fashion. We present the design concept and validation strategy for an innovative semiautomated liver segmentation method developed at our institution. Our method represents a model-based approach using variational shape interpolation and Laplacian mesh optimization techniques. It is independent of training data, requires limited user interactions and is robust to a variety of pathological cases. Further, it was designed for compatibility with both CT and MRI examinations. We evaluated the repeatability, agreement and efficiency of our semiautomated method in two retrospective cross-sectional studies. The results of our validation studies suggest that semiautomated liver segmentation can provide strong agreement and repeatability when compared to manual segmentation. Further, segmentation automation significantly shortens interaction time, thus making it suitable for daily clinical practice. Future studies may incorporate liver volumetry to determine volume-averaged biomarkers of liver disease, such as such as fat, iron or fibrosis measurements per unit volume. Segmental volumetry could also be assessed based on subsegmentation of vascular anatomy.

Keyphrases: Validation, Liver, Segmentation, Volumetry, 3D Imaging, Preoperative planning, Computed Tomography, Magnetic Resonance Imaging, Humans
Oxygenation-sensitive cardiovascular magnetic resonance imaging (OS-CMR) : potential confounding factors in use of OS-CMR

Background:  Oxygenation-sensitive cardiovascular magnetic resonance (OS-CMR) has become a feasible diagnostic imaging modality for monitoring changes of myocardial oxygenation. This technique has great potential for use as a primary diagnostic tool for cardiovascular disease, particularly non-invasive detection of ischemia. Yet, there are several potential confounding factors of this technique, some methodological, such as sequence parameters and others are physiological and not well understood. Due to T2 effects caused by tissue water content, the hydration status may impact signal intensity. This is one physiological aspect in particular that we aimed at quantifying the confounding effect by manipulating hydration status in humans and observing signal intensity (SI) changes in OS-CMR images.   Methods:  In vitro: Arterial and venous blood from eight swine were used to assess serial dilution of blood and it corresponding effect on OS sequence signal intensity. In vivo: Twenty-two healthy volunteers underwent OS-CMR. Hemoglobin (Hb) concentrations were measured at baseline and immediately following rapid crystalloid infusion of 1,000ml of Lactated Ringer’s solution (LRS). OS-CMR images were acquired in a mid-ventricular short axis view. Myocardial SI was measured during a maximal voluntary breath-hold, after a 60-second period of hyperventilation. SI changes were expressed relative to baseline (% change).  Results:  The infusion resulted in a significant decrease in measured Hb (142.5±3.3 vs. 128.8±3.3 g/L; p<0.001), while SI increased by 3.2±1.2% between baseline images at normo- and hypervolemia (p<0.05). Both hyperventilation SI and the SI changes induced by apnea were attenuated after hemodilution (p<0.05). Quantitative assessment showed a negative correlation between T2* and hemoglobin concentration (r=-0.46, p<0.005).  Conclusions:  There are several confounders to the OS-CMR technique that require attention and optimization for future larger scale clinical implementation. The hydration status in particular may be a confounder in OS-CMR imaging. Hypervolemia leads to an increase in SI at baseline and attenuates the SI response during vasoactive breathing maneuvers. This attenuation in signal intensity would need to be accounted for and corrected in clinical assessment of OS-CMR images.

Keyphrases: Oxygenation-sensitive cardiovascular magnetic resonance, Confounders, Hemoglobin, Hemodilution, Breathing-maneuvers
La violence et les traumatismes associés à la délinquance tels que vécus par les jeunes contrevenants

Young offenders who have been exposed to higher levels of violence, either by severity or frequency,  yield higher levels of delinquent behaviours and significantly more distress than those who experienced  less violence.  Victimization experiences or traumatic stressors in which a considerable amount of  violence was involved can represent life circumstances that may influence the trajectory of a persons’  delinquent behaviour. These particular experiences or stressors act as key events or turning points in an  offender’s life.  Nearly 30 years ago, literature recommended that victimization experience in violent  events should be a factor to consider in the attempt to better understand the emergence and  maintenance of violent delinquent behaviours, Literature also suggests that young offenders who have  experiences such trauma are more likely to reoffend. The limited quantity of qualitative studies  concerned by the violence and traumatic experiences as lived by young offenders themselves raises the  need to explore these events, their impacts and the ways in which they can occur in the course of a  delinquent’s career.

Keyphrases: Violence, Étude qualitative, Trauma, Juvenile delinquency, Criminal career, Qualitative study
Développement d’une méthode bio-informatique permettant de relier les gènes aux métabolites

The objective of this project was to link genes and metabolites in order to ultimately predict which metabolites to measure in order to adequately reflect the function of a given gene. Specifically, we were interested in genes, which code for proteins that regulate substrate metabolism, hence enzymes that catalyze reactions that are part of metabolic pathways. In order to quantify this link, we have developed a bioinformatics method to calculate a distance, which is defined as the number of reactions separating a given selected gene-encoded enzyme and its metabolite of interest in Kyoto Encyclopedia of Genes and Genomes (KEGG) database’s metabolic overview map. Our hypothesis was that metabolites of interest are products/substrates found at proximity of the reactions catalyzed by the selected gene-encoded enzyme. In order to test our hypothesis and validate the method, we have used genome-wide association study of metabolites levels (mGWAS) because these studies report associations between genetic variants, annotated to genes, and measured metabolites. More specifically, we used the mGWAS conducted by Shin et al. Even though the coverage of the associations reported by Shin et al. was limited (24/299), we significantly validated the proximity between gene-metabolite associated pairs (P<0.01). Overall, the method and its future developments will allow the quantitative interpretation of mGWAS associations, predict which metabolite to measure with regards to the function of a gene and, in general, enable a better understanding of the genetic control of metabolism.

Keyphrases: mGWAS, KEGG, Metabolomics, Genomics, Metabolic Pathways
La fragmentation juridique de la terre en droit privé : étude des représentations sociales et historiques de la terre dans la tradition romaniste

Until recently, legal scholars studied the specific legal model which was considered to be the best. This is the conclusion reached by comparative scholars Antonio Gambaro, Rodolfo Sacco and Louis Vogel in the first lines of Droit de l’Occident et d’ailleurs. This approach is difficult to reconcile within the context of our current globalized world. Therefore, a growing number of legal scholars have manifested a renewed interest in the strengths of different legal traditions.    Within a legal tradition a theoretical examination is sometimes necessary in order to better appreciate its wisdom. For Patrick H. Glenn, legal tradition is living and evolving. Quebec Civil law, from the Roman tradition, is the result of a process of transmission of legal knowledge whose relevance is constantly put to the test of time and social context. Early on and during all ages, those responsible for transmitting the knowledge of the Roman tradition searched for ways to define the place of human beings within nature. The relationship between humans and the land has been the subject of numerous legal reflections both within classic and modern law. The law of private property in Quebec, a fundamental branch aspect of civil law, has internalized and adapted these reflections within its particular social and historical context. The legal concept of the land has varied considerably within the Roman tradition.   This thesis proposes a study of social and historical representations of the land within the Roman tradition. It is rooted in an interdisciplinary legal approach, guided by philosophy and history. Through this analysis it will be established that the structure of property within the civil law tradition has created a legal fragmentation of the land, focused on its utilities, in order to enable human beings to derive as much as technically possible from it.

Keyphrases: Nature, Civil law, Interdisciplinary, Land, Legal history, Philosophy of law, Private law, Private property, Property right, Natural elements, Social representation
Immigration et insertion professionnelle : le cas des Haïtiens arrivés au Québec après le tremblement de terre de 2010

This thesis focuses on labor integration of Haitian immigrants arrived in Quebec after the disastrous earthquake that struck Haiti on January 12, 2010. Our goal is to analyze their professional trajectory and identify the difficulties they have faced. Our project relies on the multi-layered approach developed by Victor Piché requiring to look at macro-structural and micro-individual factors as well as the migrants social network in the study of both migration and the integration process within the host country. In this Master’s paper, we have chosen to conduct interviews with twelve Haitian immigrants. This allowed us to gather first-hand information regarding different elements that led them to the decision to immigrate and about their integration process on Quebec’s labor market. The interviews show that the respondent’s assessment regarding the quality of their socio-professional integration depends especially on micro-individual factors such as: good knowledge of both official languages, good access to information regarding available strategies for job integration, good knowledge about local practices, labor market and rules and regulation regarding immigration status and their respective possibilities. Very few of theHaitian immigrants that we met have addressed the issue of discrimination, especially because they seem to have integrated the discourse on competition and individualization that links individual factors to their successes and failures. In other words, respondents seem to have internalized this discourse urging them not only to be "good," but to be "the best" in order to compete with "Québécois de souche" on the job market.

Keyphrases: Immigration, Workforce development, Immigration wave
Tombés entre les mailles du filet : expériences de vulnérabilisation chez les jeunes en situation de rue avec antécédents de placement

Youth with a history of out-of-home placement are overrepresented among young adults who end up on the streets. What could be viewed as a failure by some is experienced as an opportunity by others: youth’s lived experience of the streets is shaped by what they’ve known prior to arriving on the streets. The goal of this research was to fill a gap in our knowledge around the connection between the lived experience of out-of-home care and the lived experience of homelessness among youth. Using the method of récits de vie, I met with six young people who were living on the streets and, as children or adolescents, had been removed from their families to be placed in out-of-home care under youth protection laws in Quebec (Canada). Their life trajectories were studied through the lens of “vulnerabilisation”: a process leading to both material impoverishment and relegation to an unfavourable social position. While in care, the young people in my study experienced three forms of vulnerabilisation: weakening of family ties, professional and social disqualification, and stigmatisation. The youth responded to these processes by accepting and identifying with their vulnerable status, by refusing or negating this status, or by rationalizing and negotiating their status. This study helps us better understand how the experience of out-of-home care and street life are connected in young people’s lives. My results could support further studies, as well as inform practices with this specific population.

Keyphrases: Itinérance, Placement, Protection, Récits de vie, Youth, Street, Homelessness, Foster care, Out-of-home placement, Protection, Lived experience, Vulnerability, Social work
Les macroinvertébrés benthiques littoraux : bioindicateurs de la qualité écologique des milieux humides en zone urbaine

Aquatic ecosystems in urban landscapes are now recognized as good islets of biodiversity and valuable environments providing ecological services. However, more knowledge is needed to assess their ecological quality. Benthic macroinvertebrates are widely used as bioindicators, but rarely for urban ecosystems. In this study, we used macroinvertebrates to evaluate the ecological quality of urban ponds and lakes in the island of Montreal. We collected macroinvertebrates during summer 2011 in the littoral zone of 20 waterbodies varying in urban and limnological characteristics. We evaluated spatio-temporal variation in several diversity and biotic indices and multiple metrics based on taxonomic composition and functional traits. We investigated if macroinvertebrate metrics responded to variation in urban land-use, pond management and limnological conditions. Our study showed that small waterbodies, as ponds, lakes and marshes are important resources for sustaining aquatic biodiversity in urban landscapes. Natural wetlands and artifical permanent ponds had higher ecological quality and supported more diverse and abundant macroinvertebrates than artificial managed temporary ponds in municipal parks. Vegetation cover, nutrient and organic contents, and algal biomass were the most important factors explaining spatial variation in macroinvertebrate metrics.  Pond management, urban density, and water permanence were also influencial factors. Univariate metrics had less potential than multivariable metrics to assess the responses of macroinvertebrates to environmental features. We discussed the implications of our study for management and quality assessment of urban ponds.

Keyphrases: Urban ecology, Littoral macroinvertebrates, Taxonomic composition, Functional traits, Bioindicators, Ponds, Biodiversity
L'incidence de l'alternance des taches sur les processus de l'attention : indices électrophysiologiques chez l'humain

Electrophysiology,   by   its   non­invasive   nature   and   excellent   temporal   resolution,   is   a   useful   tool   for   measuring   time­sensitive   cognitive   processes.   Task   switching,   which   both   increases   the   frequency   of   errors   and   introduces   an   additional   delay   in   the   performing   of   each   task,   has   been   extensively   studied   for   decades   using   purely   behavioral   paradigms.   Little   is   known,   however,   about   the   impact   of   task   switching   on   electrophysiological   indexes   of   visuospatial   attention.   In   the   present   study,   we   used   a   task­switching   paradigm   to   assess   visuospatial   attention   modulations,   using   N2pc   and   Ppc   event­related   potential   (ERP)   components   of   interest.   Our   findings   confirm   a   significant   effect   of   task   switching   on   visuospatial   attention   deployment,   mainly   indexed   by a difference in latencies between repetition tasks and switching tasks.

Keyphrases: N2pc, Ppc, MFP, task   switching, mixing   cost, electrophysiologie, electrophysiology
Associations prospectives entre l’exposition à la fumée secondaire résidentielle à l’enfance et les difficultés psychosociales à la préadolescence

Introduction. Secondhand smoke is considered a developmental neurotoxicant. Up to this day, research on secondhand smoke and later antisocial behavior has remained cross-sectional or in the developmental period of childhood.  Objective. We sough to extend previous research by extending to age 12 our prospective associational model. Also, we use self-reported data for validity reasons and to cross-match previous research using parent and teacher-rated data at age 10.  Method. Parents reported the amount of household smoke exposure (between ages 1.5 and 7) for 1035 children from the Quebec Longitudinal Study of Child Development. Main outcome measures include self-reported conduct problems, proactive aggression, reactive aggression, dropout risk, and school indiscipline at age 12.   Results. After adjusting for potential confounders, we observed that secondhand smoke is prospectively associated to conduct problems, proactive and reactive aggression, school indiscipline, and dropout risk.  Discussion. Children exposed to household smoke reported increased risks of reporting antisocial behavior at age 12. Our findings corroborate the recommendation of the American Surgeon’s General that no smoke exposure can be considered safe.

Keyphrases: Agression, Conduct problems, Dropout risk, Antisocial behavior, Tobacco smoke exposure