Plasmodium falciparum (Pf) est un parasite intracellulaire capable d’infecter l’Homme. Dans les 48h après l’invasion des érythrocytes, il passe par le stade d’une cellule géante multinucléée qui se divise en 16 à 32 parasites. Cette multiplication rapide nécessite des mécanismes spécifiques de régulation très subtilement orchestrés. Parmi les modifications post-traductionnelles décrites chez les cellules eucaryotes, la phosphorylation réversible des protéines par les kinases/phosphatases est une des voies majeures dans la transduction des signaux cellulaires. Chez Plasmodium, des études de génétique inverse ont démontré que PfPP1, phosphatase majeure du parasite, est essentielle pour sa survie. L’activité de PP1 est connue pour être contrôlée par divers régulateurs endogènes. Cependant, malgré leur importance dans le ciblage de l’holoenzyme à un compartiment subcellulaire spécifique et/ou dans la régulation de son activité, peu de recherches ont été consacrées à l’identification de partenaires de PP1 chez Pf.Dans le but d’approfondir nos connaissances sur la régulation de PfPP1 et son impact sur la biologie de Pf, nous étudions les partenaires de cette enzyme qui seraient impliqués dans le contrôle de la phosphatase. Nos recherches récentes, basées sur des études de génomique comparative, ont permis d’identifier 4 régulateurs de PfPP1 : PfLRR1, PfI3, PfI2 et PfeiF2β. Au-delà de la capacité de ces protéines à contrôler la fonction de PP1 in vitro, nous avons montré par génétique inverse que leur rôle est vital pour Pf. En parallèle, nous avons entrepris une démarche plus globale pour la recherche de nouveaux partenaires/régulateurs de PfPP1. Nous avons notamment réalisé un criblage par double hybride de levure (Y2H) où PfPP1 est utilisé comme appât.Dans la 1ère partie de ma thèse, nous avons analysé les clones obtenus en criblage Y2H et initié la caractérisation de plusieurs d’entre eux. Notre choix d’étude s’est porté par la suite sur PF3D7_091900 et PF3D7_1202600, retrouvées 8 et 10 fois lors du criblage et présentant une interaction forte avec PP1. Mon projet de thèse avait pour but de caractériser au niveau moléculaire et fonctionnel le rôle de ces protéines sur l’activité de PP1 et de déterminer les régions/motifs de ces potentiels régulateurs pouvant intervenir au niveau de la relation structure/fonction du complexe qu’ils forment avec PfPP1.Dans une 2ème partie, nous avons étudié la séquence de ces protéines. PF3D7_0919900, protéine spécifique du parasite, possède le motif RVxF, souvent impliqué dans l’interaction avec PP1 et présente des motifs RCC1 connus pour interagir avec des protéines. Ainsi elle sera nommée RCC-PIP pour Regulator of Chromosome Condensation - Phosphatase Interacting Protein. PF3D7_1202600 est, quant à elle, un orthologue de Caliban chez la drosophile, et sera nommée CLP pour Caliban-Like Protein. Elle présente 17 motifs RVxF dont 7 se situent dans le fragment obtenu suite au criblage. Différentes approches ont confirmé que ces 2 protéines sont des partenaires de PfPP1. Cependant, la réalisation d’un test pNPP in vitro a mis en évidence une fonction activatrice de RCC-PIP, alors que CLP ne présente pas d’effet.Dans une 3ème partie, l’objectif était d’étudier plus en détails RCC-PIP. Nous avons démontré que le motif RVxF est impliqué dans l’interaction avec PfPP1. Puis nous avons étudié les motifs RCC1 et leur interactome par la réalisation d’un criblage Y2H en utilisant ces motifs comme appât. Une kinase a été trouvée (PfCDPK7) suggérant que RCC-PIP aurait un rôle de plateforme capable d’interagir avec 2 enzymes antagonistes. L’étude du rôle de RCC-PIP chez le parasite est actuellement en cours. La réalisation d’un knock-in a démontré l’accessibilité du locus. Un knock-out a également été effectué, mais l’absence d’intégration du plasmide indique que RCC-PIP serait essentielle au parasite. Pour confirmer cette observation, un knock-out conditionnel chez P. berghei est en cours de réalisation. / Plasmodium falciparum is an intracellular parasite that evolves in several stages of development in the vertebrate host. Within 48 hours after the invasion of erythrocytes, it goes through the stage of a multinucleated giant cell which divides into as many parasites as nuclei (16-32 parasites). This growth/fast division requires specific regulatory mechanisms subtly orchestrated. Among the post-translational modifications described in eukaryotic cells, the reversible phosphorylation of proteins by kinases/phosphatases is one of the major pathways in the cellular signal transduction. In Plasmodium, PP1 is predicted to catalyze the majority of protein dephosphorylation events, and has been shown to be essential in its survival using reverse genetic approaches. The activity of PP1 is known to be tightly controlled by various endogenous regulators. However, despite their importance in targeting the holoenzyme to a specific subcellular compartment and/or regulating its activity, little has been devoted to identify PP1 partners in the parasite.In order to deepen our understanding of the regulation of PfPP1 and its impact on the biology of Plasmodium, we study the partners of this enzyme that may be involved in the control of its location, its specificity and activity. Our recent research, based on comparative genomic studies, have identified 4 regulators of PfPP1: PfLRR1, PfI3, PfI2 and PfeiF2β. In parallel, since Plasmodium has a particular cell cycle and the function of PP1 should be adapted, we have undertaken a more global approach to the search for new partners/regulators of PfPP1 using different approaches including a yeast two-hybrid screening where PfPP1 was used as bait.In the first part of my thesis, the clones obtained in Y2H screening were analyzed and 2 clones were selected for further characterization. These clones, corresponding to PF3D7_091900 and PF3D7_1202600 were identified 8 and 10 times during the screening, a good indication about their expression in blood stages and their interactions with PfPP1 can be still detectable under high stringency conditions. Hence, my thesis project aimed to characterize molecularly and functionally of the role of these proteins on PfPP1. _x000D_In the second part, we have analysed the sequence of these two proteins. PF3D7_0919900, a parasite-specific protein, shows the canonical binding motif « RVxF », known to be involved in the interaction with PP1, and present on the fragment obtained following the screening. The sequence also has RCC1 motifs known to interact with proteins. Thereafter, this protein was designated as RCC-PIP for Regulator of Chromosome Condensation - Phosphatase Interacting Protein. As far as PF3D7_1202600 is concerned, it seems to be an ortholog of Caliban expressed by Drosophila, and designated Pf Caliban CLP-Like Protein. It has 17 potential RVXF binding motif, of which 7 are located in the fragment obtained following the screening. Different approaches such as GST pull-down or ELISA, identified these two proteins as partners of PfPP1. Using pNPP in vitro assay, we showed a slight activation of PfPP1 by RCC-PIP, while CLP had no effect.In the third part, the objective was to study in more detail the RCC-PIP. We showed that the RVxF motif is involved in the interaction with PfPP1. We then tied to identify the partners of RCC1 by screening a cDNA library of P. falciparum using RCC1 containing protein as bait. We showed that RCC-PIP is able to interact with a kinase (PfCDPK7) suggesting that RCC-PIP may act as a platform since it is able to interact with 2 enzymes with opposed activities. Analysis of the role of RCC-PIP in the parasite is currently underway. The production of a knock-in demonstrated the accessibility of the locus. A knock-out was also carried out, but the lack of integration of the plasmid suggests that RCC-PIP is essential to the parasite. To confirm this observation, a conditional knock-out in P. berghei is in progress.

In response to the scarcity of biblical scholarship analysing the function of the Hebrew Bible’s exodus stories as persuasive communication, this dissertation investigates how these mnemonically dense stories were capable of creating and maintaining a long-term collective identity for ancient Israel. A narrative approach is selected in keeping with this intent, and the primary exodus story (Exod 1:1–15:21) and the 18 retold exodus stories found in the Hebrew Bible are identified as the focus of research. Since the tools used for analysing the narratives of non-fictional peoples need not be limited to those used for analysing literary fiction, a methodological tool—based on the principles of the social identity approach (SIA)—is developed and outlined to assist in exposing identity construction at a rhetorical level. Using the SIA heuristic tool, rhetorical formulations of identity—cognitive, evaluative, emotional, behavioural and temporal—like those occurring in face-to-face relationships, are identified in the exodus stories. These formulations make certain identity claims upon their hearers. A shared experience of oppression and deliverance is represented as the significant feature defining group membership in Israel. The literary portrayal of nine of the eighteen retold exodus stories in a setting just after the death of the adult exodus generation, asserts the importance of the appropriation of the story by a purportedly new generation. Likewise, exodus narratives with a literary setting in every major socio-cultural transition in Israel’s larger story portray Israel’s rehearsal of and participation in exodus as central and essential to her ongoing collective identity. Possible social identities offered to Israel include the temporal expansion of this ingroup based on the retelling and reappropriation of exodus and the “othering” of Israel based on non-compliance. Pre-exodus narratives are noted to have been shaped so as to include the patriarchs in “the people whom God brought out of Egypt.” Plurivocal retold exodus stories also reflects the recasting of narratives to fit identities so that, anachronistically, post-exodus members may also be included in “the people whom God brought out of Egypt.” This points to the revision and reuse of exodus narratives rather than to their unilinear development. Apart from any speculation on the historical motives of their producers, the identity-forming potential of exodus narratives characterized by the well-established, recognizable language of social identity is identified. The newly developed heuristic tool used in this analysis is its most significant contribution. It makes visible the nascent social identity language and concepts implicitly noted by prior scholarship, places them within the larger validating theoretical framework of the SIA and systematically identifies the specific persuasive elements and integrating qualities of exodus narratives.

The specific area of interest in this work is to explore decon- struction of printed motifs in relation to shape as a method of construction. One of the main objectives of this explo- ration is to change the traditional ways in which designers work with print and material in relation to form. This implies to question the structures currently present within the fashion industry as well as preconceived ideas of existing techniques, their limitations and visual appearances. What is presented in this work is how print and material can be brought forward and make out the foundation of the process. Please note that this does not imply that form comes secondary. Instead the idea is to present a method of working where these different factors have a vital connection and where form is a product of the construction and placement of print motifs. Resulting in form which is dependent on print and in turn, print which is dependent on form.

Mohammed Dib est une figure importante de la littérature algérienne de langue française; d’une stature incomparable et inégale, il appartient au courant réaliste de la première génération d’auteurs maghrébins engagés, qui renouvelle son écriture après l’indépendance de l’Algérie. L’objet du présent travail, qui s’inscrit dans le cadre du comparatisme, est d’étudier le rapport du texte dibien au modèle, en mettant en place des axes qui permettent de comparer des phénomènes d’écritures appartenant à des époques et des cultures différentes, et ce en confrontant l’écriture dibienne dans son roman Cours sur la rive sauvage et son recueil de nouvelles Le Talisman, avec La Divine Comédie de Dante, Aurélia de Gérard de Nerval et Treize histoires de Faulkner. La lecture plurielle, que nous avons appliquée au corpus, nous a permis d'approcher de manière plus directe l’univers romanesque de Mohammed Dib. La prise en compte de relation intertextuelle constitue pour nous l’outil d’analyse, permettant ainsi une réflexion sur le texte, placé dans une double perspective: relationnelle et transformationnelle précisant les enjeux d’une œuvre polyphonique.Cette étude nous a permis d’analyser les mécanismes par lesquels se traduisent les relations d’influence et de motifs littéraires, en suivant une certaine chronologie: d’abord,par rapport à Faulkner, un des écrivains américains les plus célèbres, ses oeuvres portentun intérêt particulier pour la Terre- Mère, thématique récurrente qui constitue la matrice de l’imaginaire faulknérien. Ensuite par rapport à Nerval, considéré comme l’un des plus importants romanciers du courant romantique français, du XIXème siècle. Enfin, en s’inspirant de Nerval, Dib perpétue une tradition en rapport avec la poétique de Dante, dans sa Divine Comédie, et reprend l’idée que l’écriture est un voyage initiatique. / Mohammed Dib is a special case in the French-language Algerian literature; it is the realists of the first generation of North African writers who renews his writing after the independence of Algeria. The purpose of this work that is part of the comparative report is to study the text to the model by setting up the axes that compare the phenomena of writings belonging to different eras and cultures, and by confronting the dibienne writing in his novel Course on wild shore and his short story collection The Talisman with The Divine Comedy of Dante, Gérard de Nerval Aurelia and Thirteen stories of Faulkner. The plural reading that we have applied to the corpus allowed us to approach more directly the fictional universe of Mohammed Dib. The inclusion of intertextual relationship provides us with the analysis tool, enabling reflection on the text, placed in a double perspective: relational and transformational as well as the challenges of a polyphonic work. This study allowed us to analyze the mechanisms by which the result of influence relations and literary motifs follow a certain timeline. First, compared to Faulkner, one of the most famous American writers ; its working with a particular interest for the earth- mother, the southern United States of America and the history of his country, which is the recurring theme of Faulkner's imaginary matrix. Then over Nerval, considered one of the most important novelists of the French Romantic movement of the nineteenth century. Inspired by Nerval, Dib continues a tradition related to the poetics of Dante, in his Divine Comedy, and takes up the idea that writing is a journey.

Heme proteins carry out a diverse array of functions in vivo while maintaining a well-conserved 3-over-3 α-helical structure. Human hemoglobin (Hb) is well-known for its oxygen transport function. Type 1 non-symbiotic hemoglobins (nsHb1) in plants and bacterial flavohemoglobins (fHb) from a variety of bacterial species have been predicted to carry out a nitric oxide dioxygenase function. In nsHb1 and fHb this function has been linked to protection from nitrosative stress. Herein, I combine photoacoustic calorimetry (PAC), transient absorption spectroscopy (TA), and classical molecular dynamics (cMD) simulations to characterize molecular mechanism of diatomic ligand interactions with a hexa-coordinate globin from plant (rice hemoglobin), bacterial flavohemoglobins and human hemoglobin. In rice type 1 non-symbiotic hemoglobin (rHb1), the dynamics and energetics of structural changes associated with ligand photodissociation is strongly impacted by solvent and temperature, namely CO escape from the protein matrix is slower at pH = 6.0 compare to neutral pH (ns) due to the CD loop reorganization which forms a pathway for ligand escape. In human hemoglobin, exogenous allosteric effectors modulate energetics of conformational changes associated with the CO and O2 escape although the effectors impact on rate constants for ligand association is small. The conformational dynamics associated with ligand photorelease from fHbs from Cupriavidus necator (FHP) and Staphylococcus aureus (HMPSa) are strongly modulated by the presence of azole drugs indicating that drug association modulates structural properties of the heme binding pocket. In addition, we carried out a study of the formation of the DNA intercalated motif (i-motif). The formation of the structure is strongly favored at acidic pH; therefore, PAC was combined with a 2-nitrobenzaldehyde pH-jump to probe formation of the i-motif on fast timescales. i-Motif folding is two-step process with the initial protonation of cytosine residues being endothermic with ΔHfast=8.5 ± 7.0 kcal mol-1 and ΔVfast=10.4 ± 1.6 mL mol-1 and subsequent nucleation/i-motif folding (τ = 140 ns) with ΔHslow=-51.5 ± 4.8 kcal mol-1 and ΔVslow=-6.6 ± 0.9 mL mol-1. The above results indicate that PAC can be employed to study diverse biochemical reactions such as DNA folding, drug binding and ligand photorelease from proteins.

The motif discovery problem is becoming increasingly important for molecular biologists as new sequencing technologies are producing large amounts of data, at rates which are unprecedented. The solution space for DNA motifs is too large to search with naive methods, meaning there is a need for fast and accurate motif detection tools. We propose MotifGP, a multiobjective motif discovery tool evolving regular expressions that characterize overrepresented motifs in a given input dataset. This thesis describes and evaluates a multiobjective strongly typed genetic programming algorithm for the discovery of network expressions in DNA sequences. Using 13 realistic data sets, we compare the results of our tool, MotifGP, to that of DREME, a state-of-art program. MotifGP outperforms DREME when the motifs to be sought are long, and the specificity is distributed over the length of the motif. For shorter motifs, the performance of MotifGP compares favourably with the state-of-the-art method. Finally, we discuss the advantages of multi-objective optimization in the context of this specific motif discovery problem.

Depuis les années 1950, des organismes locaux se chargent de promouvoir la destination touristique « Pays basque » français. Leurs brochures contribuent à la construction de l’imaginaire du Pays basque. Cette image(rie) touristique est vivement critiquée par une part de la population qui la juge stéréotypée et présentant une vision passéiste et immuable de la culture basque, selon eux, loin de représenter sa réalité contemporaine. Cette thèse propose d’analyser quelle est cette image(rie) touristique, par le biais des motifs qu’elle utilise, pour montrer qu’au-delà de cette critique ce sont en fait deux conceptions de la culture basque, à l’œuvre au sein même de la société basque, qui s’opposent. / Since 1950’s, local organisations undertake to promote the French “Basque country” as a touristic destination. Their brochures contribute to the Basque Country representation. This touristic image is criticized by a part of the population which judges it stereotyped and presenting a backward-looking and unchanging vision of the Basque culture, far from representing its contemporary reality. This thesis proposes to analyze what is this touristic image, via the motives it uses, to show that beyond that critique there are in fact two conceptions of the Basque culture, working inside the Basque society, which are opposed to each other.

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This thesis deals with issues of used hot plates and thick-film technology. The theoretical part of diploma thesis contains a theoretical analysis and description of corresponding technology and usage of materials. The practical part of the thesis focuses on the design of the resulting device, which forms design of the test and optimized hot element, the initial design of the device and the design of models for temperature simulations. Then follows description of the practical realization of the motifs and testing of the created thick-film structure on a ceramic substrate. In the last part are shown simulations of heat transfer in the proposed model of the device.

E. faecalis est une bactérie à gram positif, responsable d’infections nosocomiales. Dans cette étude, nous avons identifié par RNA-seq 65 ARN régulateurs potentiels induits en conditions de stress et/ou d’infection chez ce pathogène opportuniste. Parmi ceux-ci, trois ARN surexprimés in vivo, en présence de sels biliaires et à pH acide ont fait l’objet d’une étude approfondie.Le premier, SRC65, s’est avéré être un petit ARN (sARN) agissant probablement en trans. Il présenterait des fonctions redondantes avec son homologue SRC90. Différentes cibles potentielles ont été identifiées et des expériences de physiologie ont révélé un rôle de SRC65 dans le déclenchement de la phase exponentielle de croissance.Le 2ème ARN étudié est une région 5’ régulatrice non traduite (5’UTR), appelée 5’1515. Elle formerait un atténuateur et agirait de manière répressive sur le gène ef1515. EF1515 est un antiterminateur de la famille BglG/SacY capable de se fixer sur 5’1515 pour réguler son expression et celle du gène ef1516 localisé en aval et codant un système de transport des sucres de type PTS. L’antiterminateur EF1515 contrôle aussi l’expression du gène ef3023 codant une protéine impliquée dans la virulence d’E. faecalis.Le dernier ARN régulateur étudié est également une 5’UTR. Celle-ci participerait à la régulation d’une hélicase à motif DEAD (CshA) codée en aval de la 5’UTR. Sa caractérisation s’inscrit dans une étude plus large concernant les éléments du métabolisme des ARN, impliquant les ribonucléases et les autres hélicases à motif DEAD d’E. faecalis. CshA aurait un rôle prépondérant pour la bactérie, en étant impliquée dans la réponse au stress, le fitness et la virulence. L’identification de l’interactome de CshA a notamment permis d’identifier l’énolase comme partenaire privilégié. / E. faecalis is a gram-positive bacterium responsible for nosocomial infections. Using RNA-seq, we identified 65 putative regulatory RNA induced under stress and/or during infection. Of these, three RNA overexpressed in vivo, in the presence of bile salts and at acidic pH have were more deeply studied.The first, SRC65, was found to be a small RNA (sRNA) probably acting in trans. It would present redundant functions with its homologous sRNA SRC90. Different potential targets were identified and physiology experiments revealed a role for SRC65 in triggering the exponential growth phase.The 2nd studied RNA is a 5’ untranslated region (5'UTR), called 5'1515 which would form an attenuator and act repressively on the ef1515 gene. EF1515 is an antiterminator of the BglG/SacY family capable of binding at 5'1515 to regulate its expression and that of the downstream gene ef1516 encoding a PTS-type sugar transporter. The EF1515 antiterminator also controls the expression of the ef3023 gene encoding a protein involved in E. faecalis virulence.The last regulatory RNA studied is also a 5'UTR. It would participate in the regulation of a DEAD-box helicase (CshA) encoded downstream of the 5'UTR. Its characterization is part of a broader study of the elements of RNA metabolism, involving ribonucleases and other DEAD-box helicases of E. faecalis. CshA would have a prominent role for the bacteria, being involved in stress response, fitness and virulence. The identification of the CshA interactome made it possible to identify enolase as a preferred partner.