NCube/papyrus huggingface dataset:
Génomique fonctionnelle des cellules corticotropes hypophysaires : contrôle génétique de la gestion systémique des stress

The hypothalamo-pituitary-adrenal (HPA) axis regulates homeostasis in various conditions of stress contributing to both the stress response and its termination. Psychological, physical or inflammatory/infectious stresses all prompt the synthesis and secretion of hypothalamic CRH. The pituitary corticotrope cells receive this signal and in turn, secrete ACTH which triggers the synthesis of glucocorticoids (Gc) by the adrenal cortex; these steroids induce a general state of alertness in order to fight or flight aggressions and stresses. Glucocorticoids have the critical role to restrict the stress response by exerting a negative feedback on the HPA axis. ACTH is a small peptidic hormone produced after cleavage of a precursor protein: pro-opiomelanocortin (POMC). Due to its critical role in homeostasis, transcriptional control of the Pomc gene has been intensely studied during the last decades. Previous investigations identified a promoter region that is sufficient for expression of Pomc in the appropriate pituitary cells. Genome-wide studies of the Pomc locus led me to discover a novel regulatory element that is conserved throughout mammalian evolution. The activity of this enhancer is restricted to the pituitary, and more precisely to the corticotrope lineage. Interestingly, its activity depends on a novel transcription factor binding motif that binds homodimers of Tpit, a transcription factor that is only found in pituitary POMC cells. The discovery of this enhancer adds a new dimension in the control of pituitary Pomc expression. The IL6/LIF pro-inflammatory cytokines and the glucocorticoids are well known for their antagonism in control of the inflammatory response; at the Pomc promoter, their action is mediated by the transcription factors Stat3 and GR, respectively. The analysis of genomic sites bound by these two factors revealed a complex relationship and led us to define a transcription regulatory code linking these signalling pathways. In addition to their direct DNA interaction with cognate regulatory sequences, these factors iv interact with each other with different outcomes. Thus, the recruitment of GR on DNAbound Stat3 through protein:protein contacts (tethering) results in transcriptional antagonism. Conversely, Stat3 tethering to GR produces synergism; this is also the case when the two factors are co-recruited to DNA on contiguous or composite binding sites. Prolonged activation of the IL6/LIF and Gc pathways elicits a synergistic innate cell defense response in all cells and tissues. In summary, this doctoral work has defined transcriptional mechanisms that mediate and control the stress response. In particular, pituitary components of the stress response were defined at the level of the Pomc gene and as a global response of corticotrope cells. This response is critical for appropriate organism defense during stresses such as those produced in inflammatory and metabolic diseases.

Keyphrases: POMC, Stat3, GR, Tethering, ChIP-seq, Cytokine, Pituitary, Defense, Glucocorticoid
Le recyclage du déchet dans l'art du XXIe siècle : trois études de cas

This Master’s thesis focuses on the role of waste as a material in the works of three contemporary artists. The artists studied come from three different countries that do not have the same level of economic development which influences the status of waste in each of these cultures. The first artist, El Anatsui, was born in Ghana and currently lives in Nigeria. His Cloth series consists of flexible sculptures made of aluminum bottle caps that refer to traditional kente and adinkra cloth. The second artist, Vik Muniz, is Brazilian-born, but currently lives in New York. His work Pictures of Garbage (2008) is a series of portraits of the residents of Jardim Gramacho made from waste and quoting famous paintings in the history of art. The third artist, Serge Murphy, was born and works in Montreal. His installation Rien de tout cela consists of found objects, recycled and raw materials. The two versions of this work (2008 and 2009) take the idea of the cabinet of curiosities and question notions of authenticity, originality and integrity. These three artists promote a serious thought on waste by incorporating it in their artistic approach as a material worthy of being shown and not as a rejected object which must be removed from sight. We will study them within a dual process of recycled material and abstract elements (concept, tradition) that allow the transformation of waste into art: the recovery of a form (traditional kente cloth) and the material in El Anatsui; the resumption of a referent (citations of Western works) and the material in Vik Muniz; and, the recovery of a tradition (cabinet of curiosities), the work itself (auto-recycling) and the material in Serge Murphy.

Keyphrases: El Anatsui, Vik Muniz, Serge Murphy, Contemporary art, Waste, El Anatsui, Vik Muniz, Serge Murphy
La gouvernance des réseaux de politique publique : le cas du programme VIH en Haïti

This thesis focuses on the governance of public policy networks. It seeks to better understand the phenomenon through the analysis of characteristics of the network of actors involved, the challenges with respect to the governance process, and the resulting influence for interventions. The framework of analysis builds on two main theories of the sociology of organizations, namely the theory of strategic actor (Crozier and Friedberg 1977) and the theory of public policy networks (Rhodes 1997). This is about a case study of HIV/AIDS program in Haïti, documented using data from interviews, observations and focus groups. The research results are organized in four articles.  The first article shows the preliminary, but nonetheless important stage for research, that is, the fieldwork. It presents the methodological and ethical challenges inherent in the meeting between researcher and participants for the co-construction of knowledge, particularly in the context of international health research.  The second article analyzes the characteristics of the network of actors and shows the need to take into account the specific attributes of actors in addition to the structure of their interactions in understanding the governance of policy networks. Most studies on policy network, particularly those using the network approach, seek to understand how the structure of actors’ interrelations influences governance, contents or results of policies. However, in the case of HIV program in Haiti, it appears that it is the attributes of actors in terms of resources and power that shape their interactions with other actors.  The third article presents an analytical framework and shows the influence of tools and structures, as well as socio-political and economic contexts on the governance of the HIV / AIDS program in Haiti. It then argues on the challenges that this poses for the coordination of interventions and the establishment of partnerships within the network of actors.   The fourth article shows the emergence of new needs in people living with HIV (PLHIV), and highlights the weakness of the planning process to target them. It renews the interest of the participatory approach, particularly in the context of developing countries, where it has become crucial to tailor interventions to local context by using the potential and resources of communities.  The study has allowed us to show: 1) the relationship between the attributes of actors, the specific configuration of their interactions and the process of governance; 2) the challenges resulting from the influence of tools and structures erected, as well as socioeconomic and political factors, on the governance process, and finally; 3) the relationship between mode of governance - through participation - and accounting for emerging needs of PLHIV.

Keyphrases: Haïti, Governance, Policy networks, HIV program, Haiti, Case study
Facteurs environnementaux et réseaux d’eau, Arthabaska et Victoriaville, 1880-1934

This thesis focuses on the study of two separate water systems, namely that of city of Arthabaska and city of Victoriaville. We wish to clarify the role of natural and urban environmental factors in the process that led to the establishment of drinking water and wastewater systems in the two cities under consideration. Various studies have dealt with the implantation of waterworks and sewer systems across the country. However, it is mainly the large cities such as Montreal and Toronto that have caught the attention of the canadian political, urban, and environmental history.     The objective of this approach is to show that the natural physical environment must be incorporated into the analysis as a living element that transforms, which influences and is influenced in turn by humans, since both are in constant interaction. We argue that the establishment and development of water systems are influenced by the territory in which they operate and they can not be correctly analyzed otherwise. To put the surroundings in the heart of the study, we conducted an analysis of city of Arthabaska and city of Victoriaville considering the geography of the area using maps and fire insurance plans, in addition to the analysis of official documents and articles from local newspapers.

Keyphrases: Égouts, Arthabaska, Victoriaville, History, Quebec, Water systems, Waterworks, Sewer, Environment, Arthabaska, Victoriaville
Dialogue critique entre acteurs thérapeutiques : étude de la dynamique relationnelle chamanique/pentecôtiste au Guatemala

Since the second half of the 19th century, the Guatemalan religious landscape has undergone important transformations. The advent and the exceptional expansion of new protestant movements have prompted the progressive reorganization of the religious space which was, until then, relatively homogenous and triggered ideological confrontations between the various belief systems. In this tumultuous coexistence, shamanism must struggle to preserve its pertinence and to avoid falling into oblivion. By analyzing the therapeutic activity, this thesis aims at elucidating the shamanic-pentecostal relational dynamic. The portrait of the religious context and the historical developments are used as a basis for the study of the mutual perceptions between shamans, pastors and converts. This approach allows us to shed some new light onto the curanderos and brujos’ perceptions of the pentecostal pastor within the guatemalan medico-religious pluralism. However, it also allows us to deepen our understanding of the degrading perception of ancestral beliefs within the pentecostal movement. These viewpoints and the observation of the respective curative rituals thus lead me to consider closely the connections existing between these two a priori distinct universes whereas certain continuations on the therapeutic level between the two belief systems can be perceived. The field investigation finally suggests that in parallel to these perceptions and similarities, the presence of the pentecostal movement have influenced shamanic practices, leading holders of traditional knowledge to operate apparent modifications into the plan of their own ritual practices, customs and beliefs according to the pentecostal system of values.

Keyphrases: Continuation vs rupture, Guatemala, Therapeutic practices, Mutual perceptions, Continuation vs rupture, Syncretism, Repercussions, Guatemala
Modèle de mélange de lois multinormales appliqué à l'analyse de comportements et d'habiletés cognitives d'enfants

This study is about the use of mixture to model behavioral and cognitive data measured repeatedly across development in children.  Estimation of multinormal mixture models using the EM algorithm is explained in detail. This algorithm simplifies computation of mixture models because the parameters in each group are estimated separately, allowing to model covariance across time more easily. This last point is often disregarded when estimating mixture models. This study focused on the consequences of a misspecified covariance matrix when estimating the number of groups in a mixture. The main consequence is an overestimation of the number of groups, i.e. we estimate groups that do not exist. In particular, the independence assumption of the observations across time when they were in fact correlated resulted in estimating many non existing groups. This overestimation of the number of groups also resulted in an overfit of the model, i.e. we used more parameters than necessary.  Finally mixture models were fitted to behavioral and cognitive data. We fitted the data first assuming a covariance structure, then assuming independence.  In most cases, the analyses conducted assuming a covariance structure ended up having fewer groups and the results were simpler and clearer to interpret.

Keyphrases: Cognition, Multinormal mixture model, Trajectory analysis, Child development, Cognition, Behavior
Contribution de l’hypoxie et du facteur hif1a à la guérison cutanée chez le cheval

The horse is often victim of traumatic wounds for which healing can be problematic, mainly when the wound occurs on the limb. The development of exuberant granulation tissue, also known clinically as “proud flesh”, leads to extensive scarring characterized by overproduction of fibrous tissue and the absence of an epithelial cover. This scar tissue suffers from occlusion of the microcirculation within the residual granulation tissue, due to endothelial cell hypertrophy, suggesting tissue hypoxia. The presence of relative hypoxia in limb wounds of horses was recently confirmed using near infrared spectroscopy. Additionally, thermography showed decreased perfusion in limb wounds. Abundant literature incriminates "hypoxia inducible factor” (HIF) in the regulation of expression of a number of genes in response to hypoxia.  The overall objective of this research project was to define the contribution of hypoxia to problematic wound healing in horses. The first phase of the project (in vivo) aimed to measure the temporal expression of HIF1A protein in tissue samples taken from skin wounds healing normally and others developing exuberant granulation tissue and subsequent extensive scarring, according to various anatomical sites (trunk, limb). Results suggest that the expression of HIF1A within the pluricellular tissue samples of this study reflects wound epithelialization rather than tissue oxygen levels. Indeed, HIF1A appears to regulate the homeostasis and proliferation of skin keratinocytes. The second phase of the project (in vitro) consisted in the culture of equine dermal fibroblasts from the body or the limb, under conditions of normoxia or hypoxia (1% O2 or using a mimetic, CoCl2) in an effort to study their behavior (proliferation and protein synthesis). Results corroborate the contribution of hypoxia to over-scarring in the horse since hypoxia promotes both the proliferation of dermal fibroblasts and the synthesis of collagen type 1 while decreasing the synthesis of matrix metalloproteinase 2. Extrinsic factors (environmental) appear to govern the behavior of equine dermal fibroblasts since these cells behave similarly regardless of their anatomic origin (body or limb).    In summary, the two phases of the study contributed to the elucidation of a portion of the mechanisms underlying the development of exuberant granulation tissue during wound healing in horses. Further research in this area will provide a better understanding of the pathology and thus aid in the design and development of targeted therapies.

Keyphrases: HIF1A, Horse, Wound healing, Hypoxia, HIF1A, Fibroblast, Keratinocyte, Extracellular matrix
Impacts fonctionnels des variants génétiques dans les promoteurs des gènes associés à la survie et à la mort cellulaire

The regulation of apoptosis is important in maintaining cellular homeostasis and the integrity of the genetic material. Apoptosis is a cellular mechanism that eliminates damaged cells. The operation of this biological pathway is crucial to counter the spread of cells and their genetic abnormalities. Deregulation of genes encoding components of the intrinsic pathway of apoptosis is frequently observed in various types of cancers, including leukemia. We propose that functional polymorphism located in the regulatory region (rSNP) of genes involved in the intrinsic apoptosis pathway would have a significant impact in oncogenesis by altering the expression levels of these genes.  In this study, we validated, using a combination of in silico and in vitro approaches, the functional impact of genetic variability (analyzed as haplotypes, rHap) at the proximal promoters of 11 genes encoding components of the intrinsic apoptosis pathway. To do this, we subcloned the major rHaps in a vector containing the luciferase reporter gene (pGL3b). These constructs were used in transient transfection assays in three human cell lines (HeLa, Jurkat and JEG3).  We observed that at least 2 rHaps significantly influence the transcriptional activity of a specific allele. These rHaps are associated with genes YWHAB and YWHAQ. Electrophoretic mobility shift assays (EMSA) have identified 2 sites for differential DNA-protein binding with the rHaps of YWHAB. Variability in the level of expression of the genes studied could contribute to interindividual susceptibility to developing cancer, such as childhood leukemia.

Keyphrases: Cancer, Polymorphisms, Promoters, Apoptosis, Functional impact, Cancer
Analyse génétique moléculaire du gène de la voie non-canonique Frizzled/Dishevelled PRICKLE1 dans les anomalies du tube neural chez l’humain

The planar cell polarity pathway (PCP) or the non-canonical Frizzled/Dishevelled pathway controls the morphogenetic process of convergent extension (CE) that is essential during embryogenesis for gastrulation and neural tube formation. Recently, PCP signalling was associated with neural tube defects (NTD) in humans and animal models. The core PCP protein, Prickle1, is expressed in the primitive streak and mesoderm during mouse embryogenesis. Both gain and loss of function of Prickle1 cause faulty CE movements in zebrafish and the frog. PRICKLE1 physically interacts with two other core PCP members, Dishevelled and Strabismus/Vang. In the present study we investigated the role of PRICKLE1 in the aetiology of NTDs in a large cohort of 810 patients through resequencing of its open reading frame and exon-intron junctions. The pathogenicity of the identified mutations was assessed through bioinformatics methods followed by a functional validation in a zebrafish system, in vivo. We identified in our cohort a total of nine novel mutations, of which seven affected conserved amino acids: p.Ile69Thr, p.Asn81His, p.Thr275Met, p.Arg682Cys, p.Ser739Phe, p.Val550Met and p.Asp771As. These mutations were predicted to affect the function of the protein in silico and were absent in a large cohort of ethnically-matched controls. Co-injection of these variants with the wild type pk1 in zebrafish oocytes revealed that one mutation, p.Arg682Cys, antagonized the CE phenotype induced by the wild-type zebrafish prickle1a in a dominant fashion. Our study demonstrates that PRICKLE1 can represent a predisposing factor for human NTDs and further expands our knowledge on the role that PCP genes in the pathogenesis of these malformations.

Keyphrases: Prickle1, Neural tube defects, Planar cell polarity, Convergent extension, Zebrafish
Impact de l'agroenvironnement sur la qualité microbiologique des eaux récréatives dans une perspective de santé publique

Microbial pollution of recreational waters may constitute a health risk for exposed populations. Fecal contamination of these waters represents an important component of this risk, especially due to the possible presence of pathogens and exposure to antimicrobial resistant microorganisms. Sources of fecal pollution are many and include agricultural activities and animal production. This project aims to better understand agroenvironmental factors influencing the microbiological quality of recreational waters of Southern Quebec and also suggests and assesses new sources of data which may contribute to the identification of these factors.  An evaluation of the presence of antimicrobial resistant Escherichia coli in the recreational waters studied was first performed. Given the positive results found, certain bodies of waters may represent a source of antimicrobial resistant microorganisms for people engaged in water activities. However the public health impact of such exposure is still unknown.   Agroenvironmental determinants associated with the presence of antimicrobial resistant microorganisms were investigated. Results of this chapter suggest that agricultural activities, especially liquid manure spreading, may be associated with the contamination of recreational waters with antimicrobial resistant microorganisms.  The next chapter assesses key time-independent agroenvironmental determinants associated with the fecal contamination of studied recreational waters. Various variables – classified as either agricultural activities, human activities or geo-hydrological characteristics – are explored through a multivariate logistic regression model. It appears that recreational waters with ruminant productions in their proximal environment, especially when they are within a radius of 2 km, may present a higher risk of fecal contamination. A positive association was also noticed between the level of fecal contamination of a beach and its presence in an urban area. From a public health perspective, recreational waters may be contaminated by animal and human sources and these sources may represent a risk for bathers’ health.  Finally, association between fecal contamination of recreational waters and agroenvironment determinants was studied through a logistic regression model built from remote sensing data. This chapter assesses the utility of such data in the identification of these determinants and discusses the strengths and the limitations of their use in the context of the monitoring of the microbiological quality of recreational waters. In this study, positive associations were found between the level of fecal contamination and both the proximity of agricultural lands and the presence of impervious surfaces. Earth observation data may constitute an added value for the water quality monitoring program in allowing the surveillance of the determinants associated with this quality.

Keyphrases: Recreational waters, Agroenvironment, Public health, Fecal contamination, Antimicrobial resistance, Remote sensing