NCube/papyrus huggingface dataset:
La voie de régulation de la traduction de l’ARNm ASH1 : une concertation entre Khd1, Puf6 et Loc1

Directed transport mRNA localization play a role in the development, the cell motility, the synaptic plasticity and asymmetric cellular division.  In the yeast Saccharomyces cerevisiæ, this regulation mechanism is conserved among many other species.  During yeast cell division, around thirty mRNA are actively localized at the bud tip in the daughter cell.  ASH1 mRNA is the best known among them and constitutes the model used in this study. In this model, Ash1 expression is possible only after proper localization of its mRNA.  In order to do so, ASH1 mRNA translation is repressed by translational repressors during its active transport. This project investigates the mechanism of ASH1 mRNA translational regulation that is carried out by the translational repressors Khd1, Puf6 and Loc1.  Previous studies characterized the action of these factors individually.  However, in this study, we now explored the possibility of a collaboration between them.  Thus, we sought to determine if these translational repressors are part of the same ASH1 mRNA translational regulation pathway.  In addition, we tried to identify the mechanisms of recruitment of these translational repressors on ASH1 mRNA, the molecular mechanisms that initiates this process.  In this work, we show that the cytoplasmic translational repressors Khd1 and Puf6 are part of the same ASH1 mRNA translational regulation pathway.  In this pathway, the role of the nuclear translational factor Loc1 was determined by the analysis of translational factors recruitment on ASH1 in the nucleus.  We demonstrate that Puf6 and Loc1 interact in an RNA-dependent manner with the transcription machinery, via the transcription elongation factor Spt4-Spt5/DSIF.  Finally, chromatin immunoprecipitation (ChIP) assays support the model that Loc1 recruitment to nascent ASH1 mRNA is essential for the subsequent recruitment of Puf6 to this transcript.  With the results of this study and others previously done in the lab, we elaborated a recruitment model for the She2, Loc1 and Puf6 proteins on the nascent ASH1 mRNA.  In conclusion, this study has established that the translational repressors Khd1, Puf6 and Loc1 are part of the same ASH1 mRNA translational regulation pathway and allowed a better understanding of the mechanism of recruitment of translational repressors on their target mRNA.

Keyphrases: Saccharomyces cerevisiæ, Khd1, Puf6, Loc1, She2, Spt4-Spt5/DSIF, co-IP, ChIP, mRNA localization, ASH1 mRNA, yeast, asymmetric cellular division, translation regulation pathway
Characterizing cortical myosin mini-filament regulation, length and its macroscopic implications in cytokinetic dynamics

Non-muscle myosin II (myosin) is important for many cellular processes, including cytokinesis. Myosin is a major component of the contractile ring, which constricts to close the connection between the two daughter cells. It was long accepted that actomyosin contractile filament sliding closes the cytokinetic ring. However, several recent papers conclude that myosin’s actin crosslinking activity is more important than its motor activity. These two functions likely relate to the number of actin-binding heads per bipolar myosin mini-filament. I then measured the size of cortical bipolar myosin mini-filaments and tested how mini-filament size and abundance influences cytokinesis. To measure the composition of individual myosin-containing cortical features, I developed a TIRF microscopy-based assay to calculate the number of NMY-2 dimers per feature from a ratio of endogenous/functional NMY-2-GFP. Interestingly control cells possess 2 populations: mini-filaments with an average of 20 dimers and with 30 dimers that are built to consistent specifications. Depletion of the NMY-2 activator Rho-Kinase or Anillin, a contractile ring scaffold protein, significantly alters the relative abundance of small and larger NMY-2 filament populations. I then tested the macroscopic implications of perturbations that alter cortical NMY-2 assembly. I measured NMY-2 regulators depleted cells and measured NMY-2 cortical recruitment, organization, and the kinetics (speed and concentricity) of cytokinesis. Rho-K depletion decreases NMY-II cortical recruitment and organization, slows ring closure and makes it more concentric. Depletion of MRCK-1, a less well-understood conserved myosin kinase, increased myosin cortical recruitment but had little effect on furrowing kinetics. Following simultaneous depletion of MRCK and RhoK, cortical myosin organization and recruitment were drastically reduced and, as expected for a much weaker cortex, a unique concentric phenotype emerged. Thus, while Rho-kinase is the more important kinase for myosin activation, MRCK-1 contributes to myosin organization and contractile ring dynamics. We conclude that myosin is recruited to the cortex as multi-headed mini-filaments whose assembly is tightly regulated and which impacts several aspects of contractile ring function.

Keyphrases: Rho kinase, Citron kinase, Mrck-1, Anillin, Cell division, Cytokinesis, Contractile ring, Non-muscle myosin II, Microscopy
L'implication de l'autophagie dans la chimiorésistance du neuroblastome et l'intérêt de son inhibition

Neuroblastoma (NB) is a common tumor in childhood. Despite major advances in treatments, NB still have a poor prognosis with 40% of mortality. Chemoresistance is a major issue that characterizes aggressive NB. This is a consequence of an autophagic mechanism that tumor cells use to overcome stressful situations encountered during treatments. Autophagy has been the subject of several studies showing its activation in response to anticancer therapies. Its inhibition may therefore represent a very interesting therapeutic strategy for cancer treatment. The purpose of this research was to determine the presence of autophagy in NB cells and the effect of autophagy inhibition in sensitizing NB cells to conventional chemotherapy. The presence of autophagy was verified in 184 NB tumors. To determine the effect of conventional chemotherapy on autophagy, the MTT cell viability test and the autophagy measurement test (MDC, monodansylcadaverine) have been used to study 6 NB cell lines in vitro. An immunohistochemical study also allowed the verification of autophagy activation in tumors grown in mouse models. A lentivirus containing a shRNA against ATG5 was used to generate autophagy deficient cells. Using the MTT and MDC tests, we assessed their sensitivity to chemotherapy. In order to determine the effect of HCQ in sensitizing NB cells to chemotherapy, we used HCQ alone or in combination with conventional chemotherapy. This study demonstrated that autophagy is present at a basal level in NB cells. Unlike for LC3, the results showed that Beclin 1 is a factor of poor prognosis. The MTT and MDC tests have shown that vincristine, doxorubicin, cisplatin, temozolomide, rapamycin, and LY294002 induce autophagy in NB cells. Also, immunohistochemical studies showed that cisplatin treatment increased autophagy in vivo in xenograft model of human NB in mice. ATG5 deficient cells showed greater sensitivity to chemotherapy. Furthermore, the use of these cells in mouse models showed an important role of autophagy in tumor progression as well as an increased sensitivity to vincristine. Finally, combination of HCQ with conventional chemotherapy showed an increased sensitivity of NB cells to chemotherapy compared to cells receiving chemotherapy only. This study demonstrates that inhibition of autophagy in combination with conventional chemotherapy is an attractive therapeutic approach for the treatment of NB.

Keyphrases: ATG5, Neuroblastoma, Autophagy, Chemoresistance, ATG5
Investigation of the structure and dynamics of the centromeric epigenetic mark

The centromere is a unique chromosomal locus where the kinetochore is formed to mediate faithful chromosome partitioning, thus maintaining ploidy during cell division. Centromere identity is inherited via an epigenetic mechanism involving a histone H3 variant, called centromere protein-A (CENP-A) which replaces histone H3 in centromeric chromatin. Defects in the centromeric chromatin can lead to missegregation of chromosomes resulting in aneuploidy, a ¬¬frequently observed phenomenon in cancer. Moreover, deregulated CENP-A expression has also been documented in a number of human malignancies. Therefore, much effort has been devoted to uncover the structure and role of CENP-A-containing chromatin in proliferating cells. However, the molecular nature of this epigenetic mark and its potential dynamics during and outside the cell cycle remains controversial.                                                                                                                           In this thesis, the development of a novel single-molecule imaging approach based on total internal reflection fluorescence and the use of this assay to gain quantitative information about the molecular composition of CENP-A-containing nucleosomes extracted from proliferating cells throughout the cell cycle as well as the dynamics and cellular fate of CENP-A chromatin in terminal differentiation are described.  Here, we show that octameric CENP-A nucleosomes containing core Histones H2B and H4 epigenetically mark human centromeres throughout the cell cycle. Moreover, our data demonstrate that the prenucleosomal form of CENP-A bound by the chaperone HJURP transits between monomeric and dimeric forms likely reflecting intermediate steps in CENP-A nucleosomal assembly.   Moreover, quantitative analyses of centromeres in myogenic differentiation and adult mouse tissue sections revealed that centromeres undergo global changes in order to retain a minimal CENP-A epigenetic code in an inactive state, upon induction of terminal differentiation. These include a robust decrease in the number of centromeric foci, subnuclear rearrangement as well as extensive loss of CENP-A protein. Interestingly, we show that forced dedifferentiation under cell cycle reentry permissive conditions, rescued the above-mentioned phenotype concomitantly with the restoration of cell division.  Altogether, this work delineates the structural basis for the epigenetic specification of human centromeres during the cell cycle and sheds light on the cellular fate of the CENP-A epigenetic code outside the cell cycle.

Keyphrases: Nucleosomes, Chromosome, Centromere, Kinetochore, Stem cell differentiation, Single-molecule imaging, Epigenetics, Cancer, Aneuploidy, Cell cycle, Cancer, Chromosome, Kinetochore
A la rencontre de l'animal sauvage : dynamiques, usages et enjeux du récréotourisme faunique

Historically, wildlife has always been a resource for mankind by ensuring food safety to local and traditional societies. Wildlife tourism represents an evolution in the use of wildlife and affects livelihoods, culture and the local identities. The aim of this PhD research is to have a better understanding of what is wildlife tourism. This specific tourism causes a requalification of the resource, which has some impacts on human and non-human spaces, on the territorial building processes and on the relationship between men and animals. This research focuses particularly on these issues by studying wildlife viewing tourism and sport hunting tourism. These two kinds of tourism are usually in conflict because wildlife tourism is viewed as a non-consumptive tourism whereas hunting tourism is viewed as a consumptive tourism. Going beyond some common preconceptions on these different tourisms, we question the differences and/or the dialogical relationship between these practices.   To conduct this research, we chose to lead a comparative analysis putting into perspective different case studies in France and in Canada. This comparative work allows a better understanding of tourism and territorial stakes linked to wildlife tourism and it allows to reflect on the transferability of processes observed between different fieldworks. From a methodological point of view, we have defined a framework to analyse wildlife tourism. This framework is based on conceptual aspects, analysis of archives, observation methods and discourse analysis.   The first part of this work presents the theoretical context and introduces the systemic approach of this research (chapter 1, 2 and 3). These methodological and theoretical presuppositions are used to analyse how wildlife tourism dynamics act, react and retroact on the whole territorial system. The second part questions the socio-spatial organisation of wildlife viewing and hunting tourisms (chapters 4 and 5). These forms of tourisms are studied taking into account the settlement of these activities on space, the visitors’ expectations and the impacts on wildlife populations. The third and last part discusses the evolution of the relationship between humans and wildlife in time and space according to the tourism activity. Chapter 6 looks at the dialectical link between heritage processes and the uses of wildlife resource that are accepted or not, whereas chapter 7 suggests a reflection on human / animal interaction at the individual level questioning the people’s ethic in their use, behaviour and habits developed around wildlife.

Keyphrases: wildlife viewing tourism, hunting tourism, systemic, natural heritage, nature management, environmental ethics
La réalisation des devoirs par les enfants québécois de la 6e année du primaire :
variations de la participation parentale selon les caractéristiques familiales, personnelles et scolaires des enfants

A considerable amount of research has been devoted to the issue of parental involvement with homework and its importance for children’s education. In particular, studies have focused primarily on how parental homework involvement affects the academic achievement of children. However, these findings are often contradictory (Pattal, Cooper et Robinson, 2008). Given the problems of finding or probing a positive link between parental involvement and academic performance, it is important to better understand this phenomenon. In this line of thought, according to some researchers, the variation of the impact of parental involvement on school performance is mainly due to variables such as family children and schools characteristics. In this context, our study devotes to analyzing the relation between parental involvement and these three factors (family, children and school) for primary school children. First, the status of homework implementation is addressed and parental involvement with homework is analyzed in terms of frequency, duration and the relational climate between parent and child during these activities at home. Second, parents’ involvement is examined in relation to family characteristics (parental education, income, and family structure), personal characteristics (gender and performance) and school characteristics (tasks and homework required by the teacher). This research uses a database from two questionnaire surveys. The first takes place in 192 schools with 457 teachers, the second is conducted in 51 schools with 49 teachers, 848 students in sixth grade and 521 parents. Using descriptive and inferential statistics, it is possible to better determine the conditions of parental involvement in homework with primary school children and to establish which variables (family, children and school) are better predictors of the conditions of parental involvement in their child's homework. The results of this study confirm that the involvement of parents in the fulfillment of homework may vary depending on the family characteristics of children in elementary school. In addition, they show that the academic performance of the child is an important consideration in assessing parental involvement with homework factor.

Keyphrases: Parental involvement, Homework, Family characteristics, Personal characteristics, Teachers' requirements in respect of homework
The study of RNA tertiary interactions in tRNA structure and function

The role of two universally present reverse Hoogsteen U:A base pairs (RHUAs) in the T-loop and in the core of the L-shape of standard tRNA was studied. To study each of the RHUAs, bacterial in vivo genetic screens were used including the amber suppressor system (for the study of the RHUA in the T-loop) and the selenocysteine tRNA(tRNASec) system (for the study of the RHUA in the core).  These screens generated functional variants from multiple combinatorial libraries.  These variants were subsequently sequenced and subjected to a systematic analysis which included computer modeling and a type of phylogenetic analysis. The results from the amber suppressor system showed a set of functional variants which did not require the RHUA motif in the T-loop, and had replaced the standard way of interaction between the D and T loops with an interloop double helix, ILDH.  Further study culminated in the determination of an insilico model of the alternative to the standard T-loop known as type III. The results from the tRNASec system revealed that for this exceptional tRNA, the absence of RHUA (in the core) ensures an enhanced flexibility that is specifically required for tRNASec function. Thus standard tRNAs, unlike tRNASec, with the universal presence of RHUA in the core have been naturally selected to be rigid. Taken together, RHUA plays an essential role in the stabilization of tertiary interactions.

Keyphrases: ARN pliage, Instant Evolution, Computer modeling, tRNA, selenocysteine, RNA folding
Étude de l’évolution des génomes par duplications, pertes et réarrangements

Gene duplication is one of the most important types of events affecting genomes during their evolution because it can create novel gene function. During the evolution process, genomes are also affected by inversions, translocations (including chromosome fusions and fissions), transpositions and deletions. Studying the evolution of genomes is important to get a better understanding of the biological mechanisms involved, which types of events are more frequent than others and what was the gene content in the ancestral species just to name a few. In order to analyze these different aspects of genome evolution, efficient algorithms need to be developed to infer ancestral genomes, evolutionary histories, homology relationships between genes and to compute distances between genomes. In this thesis, four different projects related to the study and analysis of genome evolution are presented: 1) We developed two algorithms to solve problems related to whole genome duplication: one that generalizes the genome halving problem to gene losses, and one that allows to compute the double distance with losses. 2) We developed a new method to infer evolutionary histories of orthologous tandemly arrayed gene clusters. 3) We proposed a new graph-theoretic approach to infer inparalogs that simultaneously considers the information given by multiple species in order to make better inferences of inparalogous gene pairs. 4) We studied the evolutionary history of the tRNA genes of 50 Bacillus strains.

Keyphrases: Duplication, Algorithm, Inference, Evolutionary history, Ancestral genome, Homology, Inparalogy, Genomic rearrangement, Loss
Prévalence d’excrétion de Giardia et Cryptosporidium chez les humains, les animaux domestiques et les lémuriens de l’écosystème du Parc National de Ranomafana, Madagascar

Increasing human activities in the vicinities of natural habitats may facilitate the emergence and transmission of diseases between humans and domestic animals and wildlife species. We conducted a cross-sectional study investigating the prevalence of Giardia and Cryptosporidium, two ubiquitous and potentially zoonotic protozoan parasites in various populations of humans and animals from the Ranomafana National Park ecosystem (RNP), Madagascar. Fecal samples were obtained non-invasively from human volunteers, domestic animals and introduced rodents inhabiting three villages in the vicinity of the national park and from four species of free-ranging lemurs (Propithecus edwardsi, Prolemur simus, Eulemur rubriventer and Microcebus rufus) from the RNP. Samples were analyzed using the direct immunofluorescence technique. Prevalences of Giardia and Cryptosporidium were estimated and variables associated with infections by the protozoa were identified. Cryptosporidium and Giardia were detected with a prevalence of 22.9 % and 13.6 % in humans respectively. The prevalences of these two parasites varied from 0 % to 60 % in domestic animals and introduced rodents from the villages. Species, age category and co-infection with the other protozoan were significantly associated with the infection by Cryptosporidium and Giardia in this ecosystem, whereas coinfections by different helminths order were not significantly associated with Cryptosporidium or Giardia. Moreover, Cryptosporidium was detected in 10.5 % of lemurs sampled from the RNP. This study reports for the first time the occurrence of Cryptosporidium in two species of lemurs from the RNP. Giardia was not detected in fecal samples from lemurs inhabiting the RNP.

Keyphrases: Cryptosporidium, Giardia, Lémuriens, Parasites, Madagascar, Lemurs, Protozoan, Epidemiology
Modèle de confiance et ontologie probabiliste pilotés par réseaux bayésiens pour la gestion des accords de services dans l’environnement de services infonuagiques

Cloud Computing is a new paradigm of IT on-demand services which has experienced tremendous growth over the past decade. The provider of Cloud computing services   describes the service to be provided, its cost, and penalties for service violations within a document. This document is called Service Level Agreement (SLA). The signature of this contract by the customer and the provider guarantees the quality of service received by the customer. It also entails the provider to manage its resources efficiently to meet its commitments. Unfortunately, the SLA violation is common; it is usually caused by uncertainty about customer behavior that can make variable number of requests assuming that resources are boundless. This behavior may have an impact on the availability of the service, thus its related SLA. Repeated SLA violations will definitively have an impact on the trust level that the customer has about the provider that might no longer enjoys a good reputation in meeting its commitments. To cope with these problems, we have proposed a Framework driven by a Bayesian network that allows, first, to classify the suppliers in a Cloud directory according to their trust level. This directory can be managed by a third party entity, in which a client will choose a provider before starting SLA negotiation. Secondly, we have developed a probabilistic ontology, based on a Multi-Entity Bayesian network, which takes into account uncertainty, in the customer behavior, and makes predictions by inference; these predictions help preventing SLA violations based on historical data.. The results show the effectiveness of the probabilistic ontology for the prediction of SLA violations in a Cloud Computing environment.

Keyphrases: SLA, Cloud computing, Bayesian network, Cloud-directory, Probabilistic ontology, Trust model