NCube/papyrus huggingface dataset:
Caractérisation du système d’acquisition de fer codé par le locus iro chez Salmonella enterica sérovar Typhi

Iron is an essential element for most bacteria. Since they are unable to synthetize it themselves, bacteria have developed systems to acquire iron from the environment or from host, for their own metabolic needs. Different strategies coexist in the same pathogen as a result of the low iron concentration available in the environment and in their host. Salmonella enterica serovar Typhi (S. Typhi) is a Gram negative entericbacteria that causes a systemic disease called typhoid fever, which is specific to humans. The pathogenic mechanisms of this serovar remain poorly characterized due to its tropism for humans and the lack of an adequate animal model. The objective of this project is to characterize the iron uptake system encoded by the iro locus of S. Typhi. The iroBDCEN genes of this locus are well known in other pathogens, especially in E. coli and Salmonella Typhimurium. Even if a role in virulence has been established for this locus in several bacteria, it has not been verified in S. Typhi, which importantly uses the systemic route of infection. We evaluated the role of synthesis, export and import of the salmochelin siderophores coded by the iroBCDEN genes. Inactivating the whole locus and each individual gene by allelic exchange, provided a means to observe their effects in vitro by infecting human cells. The role in adhesion and invasion of epithelial cells and their role in phagocytosis and survival in macrophages were determined. Moreover, the secretion mechanism by which salmochelin siderophores are able to pass through the external membrane is unknown to date. The TolC efflux pump is responsible for secretion of several molecules, including enterobactin, a siderophore related to salmochelins. By mutagenesis, we created a tolC deletion mutant to verify its implication in interactions with epithelial cells and macrophages. To characterize the mutants in vitro, we tested their ability to grow in different media. Sensitivity to hydrogen peroxide was verified for all mutants and due to the infection results for ΔtolC, we tested the motility of this mutant. These experiments allowed a better understanding of the implication of the iro locus, its components and the efflux pump TolC with human host cells that are targeted during systemic infection caused by Salmonella Typhi.

Keyphrases: Salmonella, Fer, Iron, Siderophore, Salmochelin
L’impact de l’inhibition de la iNOS et de la kininase I dans les effets délétères du récepteur B1 des kinines dans le diabète de type 2

Kinins are vasoactive peptides and central neuromediators involved in several biological and inflammatory processes. They act on two types of receptors (R) coupled to G proteins, B2R constitutive and B1R which is induced by oxidative stress and pro-inflammatory cytokines via the transcriptional nuclear factor, NF-kB. The B1R is a potent activator of iNOS and increases its expression in insulino-resistant rat. In this model of rats subjected to a diet rich in D-glucose, a treatment for one week with a non-peptide B1R antagonist, SSR240612, reverses most of diabetic complications in insulino-resistant rats. These studies lead us to hypothesize that iNOS contributes to the deleterious effects of B1R in insulino-resistant rats. We therefore have evaluated the effects of a one-week treatment with either 1400W (1 mg/kg x twice/day), a selective inhibitor of iNOS, or Mergetpa (1 mg/kg x twice/day), a nonselective inhibitor of carboxypeptidase M (CPM), which suppresses the formation of B1R agonists. These treatments should reproduce the deleterious effect of the B1R antagonist (SSR240612). Indeed, 1400W and Mergetpa normalize hyperglycemia, insulin resistance (HOMA index), cold allodynia and the expression of several markers of inflammation (COX-2, iNOS, B1R, IL-1, superoxide anion). These results support the contribution of iNOS in the deleterious effects of B1R in insulino-resistant rats. Another aspect of this thesis aims to understand the impact of B1R inhibition by SSR240612 (10 μg/g/day) combined or not with Pioglitazone (1.6 mg/g/day) (an anti-diabetic of the family thiazolidinediones, TZD) in a model of type 2 diabetes associated with obesity in C57BL/6J mice subjected to a high-fat diet for a period of twenty weeks. The treatment for two weeks with TZD normalizes glucose tolerance and plasma insulin viii levels while SSR has no effect. The combined treatment with TZD and SSR further reduces the loss of insulin sensitivity and reduces plasma levels of leptin. The results obtained suggest that SSR does not provide the expected beneficial effects, in this advanced type 2 diabetic model, in contrast to the insulino-resistant (pre-diabetic). rat model.

Keyphrases: adiposity, allodynia, hyperglycemia, obesity, insulin resistance
Les dispositifs d’aide à la consommation : une analyse qui prend compte des obstacles à la rationalité dans l’évaluation des biens de consommation

This research project aims at exploring the role of design within the act of purchasing and rating products. This premise is based on the fact that design is an obstacle to an individual’s rationality when choosing goods because they are multidimensional and of uncertain quality, as proposed by Lucien Karpik. This creates a difficulty faced by consumers when trying to find comparable products on the market. The research hypothesis of this project suggests that design is an obstacle to reason by offering multidimensional products to consumers. It then becomes harder for them to evaluate singular products available on the market, and to make wise consumption choices. One of the aims of design is to offer users freedom of choice, but this dynamic and economic role of design can also lead to confusion, where consumers become blinded by the abundance of choices. In this sense, design would be the keystone of a singularity-based economy. Five product rating projects were observed on a two-year period within two agencies involved in producing consumption aid devices by using an ethnological approach. The conclusion of this study has shown that some improvements could be made to the product rating processes, particularly for the facts that have not been accounted for in the actual consumption aid devices, such as user-centered product ratings based on user scenarios instead of object-centered product ratings, as well as considering user experience in product evaluation.

Keyphrases: economics of singular goods, design economy, consumption, product evaluation, product rating, confidence, trust, user-centered design (UCD), user experience design (UX), consumption aid device
Documenter les façons de faire d'enseignants de la 6e année du primaire dans toutes les étapes de la démarche d'évaluation

The paradigm shift brought by the competency-based approach in the educational system of Québec at the beginning of this millennium has compelled teachers to adopt new practices prescribed by the Politique en évaluation des apprentissages (MEQ, 2003) geared towards promoting assessment for learning. On her part, Brookhart (2004) suggests that research concerning learning and assessment in primary schools are limited and Boutin (2007) is unsure whether teachers have really changed their teaching practices because there were sharp criticisms as regards the implementation of the competency-based approach in the schools of Québec. This research therefore aims to shed light on the practices of 6th grade teachers in all the stages of the evaluation process in reading, writing and mathematics. We will also assess whether the practices adopted are found in the traditional or new perspectives and whether the frequency of the items related to their practices differ according to the personal characteristics of teachers. Using a concurrent nested design, 55 teachers filled in a questionnaire and 14 of them participated in semi-structured interviews. Data analysis reveals that all along the evaluation process, teaching practices vary, and in all three disciplines: they use practices found on a continuum from the traditional to the new perspectives of assessment in the planning, data collection, interpretation and communication phases and use new perspectives in the judgement phase, depending on their personal characteristics. We have thus been able to categorise these teachers using the model of Schwartz, Bransford and Sears (2005) by distinguishing less efficient teachers from those who really are even if all innovate in their practices. In order to enhance teacher practices at each phase of the evaluation process, we feel it would be interesting to validate a table inspired by Scallon (2004) and the OECD (2005) with the aim of creating a rubric used for analysing the relevance of and consistency in teaching practices throughout the school year, when assessment should be integrated to learning.

Keyphrases: assessment integrated to learning, evaluation process, primary schooling, french and mathematics
Étude de l’activité des présumés IRES de l’ARN messager de p53

p53 is a transcription factor that plays a crucial role in tumor suppression and cellular senescence. According to the literature, the p53 mRNA contains two internal ribosome entry sites (IRES), one in the 5’ untranslated region and the other one at the beginning of the coding region. The two IRES should enable the synthesis of p53 to occur under stress conditions, such as senescence. The aim of our study was to identify the key elements that control the activity of the two p53 IRES and to study their behavior in senescence. We constructed two dicistronic vectors containing the Renilla luciferase gene (Rluc), which is translated in a classical cap-dependent manner, an intercistronic region containing one of the two IRESs sequences of p53, and the firefly luciferase gene (Fluc), whose translation depends on the IRES in the intercistronic region. The IRES activity was assessed by the ratio between the two luciferase activities (Fluc/Rluc) in cell extracts from HEK293T and primary human fibroblasts. We also inserted a structure preceding the IRES sequence that prevented readthrough or translation reinitiation, which could lead to Fluc synthesis. We verified the absence of cryptic promoter in the two IRES sequences. We also constructed vectors containing the reverse complement region of each of the two p53 IRES (called SERI). We found that the efficiency of translation of Fluc via IRES sequences or via SERI sequences is similar. In addition, the level of Fluc translated via the presumed p53 IRES represents only 1% of the level of Fluc translated in a cap-dependent manner. The activities of so-called IRES of the p53 messenger do not increase in senescent human fibroblasts. Finally, the introduction of a structured region in the 5'UTR of the dicistronic messenger repressed not only the cap-dependent translation of Rluc but also the IRES-dependent translation of Fluc. Our results lead us to conclude that the p53 messenger does not contain any IRES and suggest that the low Fluc activity observed results from a cryptic splicing producing a messenger whose translation generates a portion of Rluc fused to Fluc. Our results are consistent with data reported in the literature showing that the existence of most cellular IRES is disputed. A set of stringent controls must be applied to the study of any presumed IRES before asserting its existence. The two-luciferase reporter, considered as the model of choice for studying IRES-translation, can in fact reveal various abnormalities of gene expression.

Keyphrases: P53, IRES-dependent initiation, Senescence, Aging
Étude in vivo de la relation entre la structure et la fonction de la boucle variable de l'ARN de transfert de la sélénocystéine d'E. coli

Selenocysteine is the 21st genetically encoded amino acid and is found across the three domains of life. It is synthesized on the tRNA-Sec by a single process. The tRNA-Sec also stands out at the structural level. The acceptor stem has 8 (bacteria) and 9 (eukaryote) base pairs, in contrast to canonical tRNA which invariably has 7 base pairs in the acceptor stem. Furthermore, the D-stem has two additional bases pairs which replace the universal tertiary interactions 8-14, 15-48 which are absent in the tRNA-Sec. On the other hand, the length of the extra-arm of tRNA-Sec is longer than the majority of type II tRNA . In this dissertation, we focus on the extra-arm of tRNA-Sec. The research consists of distinguishing the base pairs of the extra-arm that are essential for the biosynthesis and insertion of selenocysteine. In addition, we examine if the additional base pair in the acceptor stem (bacteria) is essential for the insertion of selenocysteine. To study these questions, we used the experimental Instant Evolution approach which consists of the in vivo screening of functional tRNA-Sec clones in E. coli. In this work, it is shown that the insertion of selenocysteine does not require a specific length or sequence of the tRNA-Sec. It is also shown that neither the length of the acceptor stem or of the acceptor/T domain is required to have a functional tRNA-Sec .

Keyphrases: Selenocysteine, tRNA, tRNA-Sec, Extra-arm, Acceptor stem, Instant evolution
La saturation de la mémoire auditive à court terme, une étude en électrophysiologie

The aim of the current study is to further understand, through the use of event-related potentials (ERPs), the neural mechanisms that underlie the maintenance of pitch in auditory short-term memory (ASTM) after reaching the memory span. Two behavioral experiments were used to help perform the selection of the participants: the first one was an evaluation of the acoustic discrimination and the second one was a general evaluation of participants’ ability to succeed to a similar task of the one that will be used in the electrophysiological (EEG) part of the experiment. Behavioral results from the EEG task showed a significant decrease in accuracy when the load increased (sequences of 2, 4, 6 and 8 tones). The estimation of the memory capacity (named K), increased from load 2 to 4 and reached a plateau after 4 tones. The maximum K represented 2.84 tones; the auditory span seems to be around 3 tones. Experimental results showed that the ERP component related to the maintenance of tones in ASTM, as measured by the Sustained Anterior Negativity (SAN), was modulated by the load. More specifically, its amplitude increased when the load increased (from 2 to 4) and reached a plateau at load 4. These results suggest that the maintenance of additional tones in ASTM is not possible after its saturation. Thus, the SAN appears to be an adequate electrophysiological index of neuronal activity related to the maintenance of tones in ASTM, and its amplitude appears to be predicted by K. Post-hoc results showed that musician and non-musicians tend to have some differences in their electrophysiological results; however, no change related to the load effect was observed. Finally, a qualitative and quantitative analysis was done to investigate the impact of the use of different mnemonic strategies in ASTM. Taking together, our results support that the SAN component is related to the maintenance of tones in ASTM and can be considerate as a good indicator of its capacity.

Keyphrases: Auditory short-term memory (ASTM), Electrophysiology (e.g. EEG), Event-related potentials (ERPs), Auditory span, Mnemonic strategies
Characterization of the Sterile20 kinase Slik : A regulator of growth in Drosophila

Cell proliferation and tissue growth are tightly controlled during development. In epithelial tissues in Drosophila melanogaster, these processes are regulated in part by the Sterile-20 kinase Slik (SLK and LOK in mammals) and the tumor suppressor Hippo (Hpo, MST1/2 in mammals). Slik overexpression leads to an increase in tissue size in flies, whereas, slik-/- mutants die before completing development. Overexpressing this protein in the developing wing disc epithelium promotes cell proliferation, consistent with the overgrown wing phenotype in the adults. Moreover, expression of Slik in one population of cells leads to an overproliferation of neighboring cells, even when they are physically separated by a central lumen. This can be explained by secretion of paracrine growth factors, stimulating non-autonomous proliferation that is specific to Slik. We used genetic and transcriptomic assays to define the molecules and mechanism involved in Slik-mediated signaling. Contrary to what has been suggested, we found that Slik does not promote proliferation through the tumor suppressor Merlin (Mer, NF2 in mammals), an upstream component of the Hippo pathway, nor through other components of the Hippo pathway. Rather, Slik promotes non-autonomous proliferation and tissue growth signaling through dRaf (the single Raf family kinase orthologue in Drosophila). We found that dRaf is required in the signal receiving cells to stimulate proliferation. We performed RNA-seq to identify novel downstream effectors of Slik. Characterizing the signaling pathway downstream of Slik in Drosophila will shed light on how SLK and LOK function in mammals, and provide insights into their potential involvement during development and in cancer.

Keyphrases: Slik, Hippo, Merlin, Raf, Proliferation, Growth, Epithelial cell
Rôle des associations de quartier dans l’organisation des services publics  dans les quartiers précaires à Port-au-Prince : Une étude de cas à Village Solidarité

Port-au-Prince, the biggest city of the Caribbean considering the size of its  population, is mostly constituted in precarious neighborhoods generally named  “bidonvilles”. Those neighborhoods generally built over dangerous fields, by a  population that is looking for affordable housing are the place of living of the  majority of the inhabitants of the city. At the same time, they represent the true  places to observe the unthinkable imagination of the local populations to organize  access to some basic services. Through the action of a local association in Village  Solidarité in the metropolitan area of Port-au-Prince, we studied the contributions  and the limits of the used strategies to organize public services of electricity.    The overall analysis is conducted under a local development approach that is  constructed around the concepts of common goal, belonging and collective  identity, leadership, resource and political opportunity. A sample of association  members and residents has participated in group focus and individual interviews  during the field study.    The results of the research are expressing an imprecise common goal and an  insufficiency of the ideological instruments, and the material and financial  resources. The leadership is prisoned by religious frame of thinking, local political  tricks, and infantilized by the action of governmental actions. At the end, we  propose paths to strengthen the power of the neighborhood toward a collective  project. Those paths are constructed fundamentally over the transformation of the  sets of thinking and organizational practices.

Keyphrases: Port-au-Prince, Precarious neighborhood, Neighborhood association, Community action
The comorbidity of psychopathy, anxiety, and depression disorder

Psychopathy is a personality disorder characterized by behavioral traits that are often considered undesirable. These traits include callousness, lack of empathy, narcissism, and increased sense of self-worth. These characteristics of psychopathy manifest themselves in men and women alike, and within both criminal and noncriminal populations. The study of the relationship between psychopathy and other mental disorders is a relatively new area of research within the field of psychology. The present study attempted to expand this area of research, namely by examining the relationship between psychopathy, anxiety, and depression. Studies conducted on this relationship have thus far shown that both anxiety and depression disorder are significantly and negatively correlated with psychopathy. For the present study, a total of 92 currently enrolled or recently graduated undergraduate and graduate students were recruited for participation. The participants completed four standardized scales that assessed their level of psychopathy, anxiety, and depression disorder. Participants were assessed using the Levenson’s Self-Report Psychopathy scale, the Childhood and Adolescent Taxon Self-Report, the Beck Depression Inventory, and the Beck Anxiety Inventory. The results suggested that both anxiety and depression are positively and significantly correlated with psychopathy as well as with each other. Additional variables, such as gender and educational origins, were found to contribute significantly to the model. The discussion of the results of the present study includes the findings of previous, related research as well as the importance of psychopathic comorbidity analyses in future research.

Keyphrases: Psychopathy, Anxiety, Depression, Comorbidity, Noncriminal
A study of chymotrypsin immobilization conditions for improved peptide mapping

Peptide mapping is an important technique used in conjunction with other methods to identify proteins and characterize post-translational modifications. To cleave proteins into small peptides for mapping, chemical and/or enzymatic methods are used. In the present study, the enzyme chymotrypsin was used for hydrolysis (digestion) of peptide bonds. A drawback of using soluble enzyme is autoproteolysis, the formation of peptides coming from chymotrypsin, giving unwanted peaks in the peptide map of the protein substrate. Therefore, making chymotrypsin immobile by cross-linking it with glutaraldehyde (GA) to avoid unwanted autoproteolysis peaks has been used in the present work. GA cross-linking for enzyme immobilization was carried out based on a method described previously in the Waldron group. Capillary electrophoresis (CE) was used for separation of the peptides (i.e., peptide mapping) as a way to evaluate digestion efficiency of soluble versus immobilized chymotrypsin. To investigate the best conditions for digestion of protein substrate by free (soluble) versus GA-cross-linked chymotrypsin prior to analysis by CE, two different buffers were evaluated (ammonium bicarbonate and Tris-HCl). The maps of autoproteolysis peptides were compared between the two chymotrypsin formats. To improve the peptide maps obtained by CE, again using autoproteolysis of chymotrypsin without substrate present, three methods for capillary conditioning and two methods for terminating the digestion were investigated. Ammonium bicarbonate was found to be the best digestion buffer and a dry ice/acetone bath was the best method for stopping the digestion, with both of these giving better CE-based peptide maps. Adding 25 mM SDS in the post-conditioning capillary rinse was demonstrated to further improve peptide mapping. The autoproteolysis of soluble and GA-chymotrypsin were compared under 6 different conditions of digestion time (30 and 240 min) and temperature (4, 24 and 37ºC). Under these conditions, our results confirmed that the GA-cross-linking reduces chymotrypsin autoproteolysis compared to the free enzyme. Digestion (at 37ºC/240 min) of two model substrates with free or immobilized chymotrypsin as a function of heat-induced denaturation of substrate was studied. Prior to digestion, the substrates (bovine serum albumin, BSA, and myoglobin) were denatured by v heating for 45 min at three different temperatures (60, 75, and 90ºC). The results showed heat-induced denaturation of BSA and myoglobin did not improve peptide maps when using GA-chymotrypsin digestion compared to using free chymotrypsin, although the latter improved with heat-induced denaturation at higher temperatures. Therefore, heating the substrate to 90ºC and using soluble enzyme provided some unfolding of substrate and limited digestion, which was better for myoglobin than for BSA.

Keyphrases: Peptide mapping, Cross-linking, Glutaraldehyde, Chymotrypsin, Capillary electrophoresis