La pestivirose de l'Isard (Rupicapra pyrenaica pyrenaica) (description clinique et épidémiologique en Ariège-Pÿrénées)

La réduction des effectifs d isards observée ces dernières années dans les Pyrénées s explique par la découverte d une nouvelle entité infectieuse : Un virus du genre Pestivirus est isolé chez plusieurs individus. L étude clinique et nécropsique réalisée chez dix sept isards malades collectés dans les Pyrénées ariégeoises permet de décrire précisément les modalités d expression de la maladie dans cette espèce. Des analyses sérologiques et virologiques permettent de classer ce virus au sein des Border Disease Virus dans un nouveau génotype : le BDV-4.TOULOUSE-EN Vétérinaire (315552301) / SudocTOULOUSE3-BU Santé-Centrale (315552105) / SudocSudocFranceF

Optimization based on the study of trajectories in a random environment : application to the control of production systems

Dans le contexte international actuel, les entreprises doivent être capables de développer des stratégies leur permettant d’augmenter leurs performances et d'être plus compétitives. Cet environnement très évolutif introduit de nombreuses incertitudes et contraintes qui rendent beaucoup plus difficile la détermination de la meilleure stratégie à adopter selon les objectifs fixés. Le travail développé dans cette thèse, s’inscrit dans ce cadre et nous nous intéressons plus précisément à l'optimisation du pilotage de systèmes de production soumis à aléas (comme les pannes des machines) de façon à minimiser les coûts globaux. Pour la modélisation, le modèle à flux continus est choisi afin de représenter le flux de matières transitant dans le système. Ce modèle, nous permet également d'intégrer les délais de transfert et de transport entre les différents éléments qui composent le système.La méthode de résolution analytique utilisée est issue des méthodes d’analyse de sensibilité et correspond à la méthode d’analyse des perturbations infinitésimales (IPA). Cette méthode nous permet de déduire à partir d'une étude de trajectoires, un gradient du coût global pour chacune des études menées. Nous prouvons alors que ces gradients ne sont pas biaisés. Cela nous permet de les utiliser dans des simulations numériques. Ces simulations nous permettent de déterminer les variables de décision des stratégies de pilotage du système considéré. Le pilotage intègre la maintenance à la production. Pour le pilotage des systèmes considérés, nous considérons également des contraintes liées aux trois piliers du développement durable. Ces contraintes sont intégrées à nos modèles sous forme de coûts. Ainsi, les coûts globaux peuvent comporter en plus de coûts purement économiques, des coûts environnementaux et sociaux. Nous montrons donc que l'approche de résolution proposée peut être utilisée pour optimiser d'autres objectifs dans un cadre de durabilitéIn the current international context, companies need to be able to develop strategies to increase their performance and become more competitive. This rapidly changing environment introduces many uncertainties and constraints, making much more difficult to determine the best strategy according to the objectives set. The work developed in this thesis falls within this context and, more precisely, we are interested in the optimization of the control of production systems subject to uncertainties (such as machine failures) in order to minimize the overall costs. For modeling, the continuous-flow model is chosen to represent the material flow moving through the system. This model allows us to integrate transfer and transportation delays between the different components of the system. The analytical resolution method used is based on the sensitivity analysis methods and corresponds to the infinitesimal perturbation analysis method (IPA). This method allows us to deduce, based on learning from sample-paths, a gradient of the overall cost for each of the studies conducted. We prove that these gradients are unbiased, which allows us to use them in numerical simulations. The simulations allow us to determine the decision variables of control strategies of the studied systems. The control integrates the maintenance to the production. For the control of the considered systems, we also take into account constraints linked to the three pillars of sustainable development. These constraints are integrated into our models in terms of costs. Thus, the overall costs may not only include purely economic costs, but also environmental and social costs. We show that the proposed resolution approach may be used to optimize other objectives within a sustainability framewor

Transfer RNA: from pioneering crystallographic studies to contemporary tRNA biology.

Transfer RNAs (tRNAs) play a key role in protein synthesis as adaptor molecules between messenger RNA and protein sequences on the ribosome. Their discovery in the early sixties provoked a worldwide infatuation with the study of their architecture and their function in the decoding of genetic information. tRNAs are also emblematic molecules in crystallography: the determination of the first tRNA crystal structures represented a milestone in structural biology and tRNAs were for a long period the sole source of information on RNA folding, architecture, and post-transcriptional modifications. Crystallographic data on tRNAs in complex with aminoacyl-tRNA synthetases (aaRSs) also provided the first insight into protein:RNA interactions. Beyond the translation process and the history of structural investigations on tRNA, this review also illustrates the renewal of tRNA biology with the discovery of a growing number of tRNA partners in the cell, the involvement of tRNAs in a variety of regulatory and metabolic pathways, and emerging applications in biotechnology and synthetic biology

Biophysical analysis of Arabidopsis protein-only RNase P alone and in complex with tRNA provides a refined model of tRNA binding

RNase P is a universal enzyme that removes 5 leader sequences from tRNA precursors. The enzyme is therefore essential for maturation of functional tRNAs and mRNA translation. RNase P represents a unique example of an enzyme that can occur either as ribonucleoprotein or as protein alone. The latter form of the enzyme, called protein-only RNase P (PRORP), is widespread in eukaryotes in which it can provide organellar or nuclear RNase P activities. Here, we have focused on Arabidopsis nuclear PRORP2 and its interaction with tRNA substrates. Affinity measurements helped assess the respective importance of individual pentatricopeptide repeat motifs in PRORP2 for RNA binding. We characterized the PRORP2 structure by X-ray crystallography and by small-angle X-ray scattering in solution as well as that of its complex with a tRNA precursor by small-angle X-ray scattering. Of note, our study reports the first structural data of a PRORP-tRNA complex. Combined with complementary biochemical and biophysical analyses, our structural data suggest that PRORP2 undergoes conformational changes to accommodate its substrate. In particular, the catalytic domain and the RNA-binding domain can move around a central hinge. Altogether, this work provides a refined model of the PRORP-tRNA complex that illustrates how protein-only RNase P enzymes specifically bind tRNA and highlights the contribution of protein dynamics to achieve this specific interaction

Determination of protein‐only RNase P interactome in Arabidopsis mitochondria and chloroplasts identifies a complex between PRORP1 and another NYN domain nuclease

International audienc

Biophysical analysis of Arabidopsis protein-only RNase P alone and in complex with tRNA provides a refined model of tRNA binding

RNase P is a universal enzyme that removes 5' leader sequences from tRNA precursors. The enzyme is therefore essential for maturation of functional tRNAs and mRNA translation. RNase P represents a unique example of an enzyme that can occur either as ribonucleoprotein or as protein alone. The latter form of the enzyme called PRORP (PRotein-Only RNase P) is widespread in eukaryotes, in which it can provide organellar or nuclear RNase P activities. Here, we have focused on Arabidopsis nuclear PRORP2 and its interaction with tRNA substrates. Affinity measurements helped assess the respective importance of individual pentatricopeptide repeat motifs in PRORP2 for RNA binding. We characterized the PRORP2 structure by X-ray crystallography and by small-angle X-ray scattering (SAXS) in solution, as well as that of its complex with a tRNA precursor by SAXS. Of note, our study reports the first structural data of a PRORP-tRNA complex. Combined with complementary biochemical and biophysical analyses, our structural data suggest that PRORP2 undergoes conformational changes to accommodate its substrate. In particular, the catalytic domain and the RNA binding domain can move around a central hinge. Altogether, this work provides a refined model of the PRORP-tRNA complex that illustrates how protein-only RNase P enzymes specifically bind tRNA and highlights the contribution of protein dynamics to achieve this specific interaction

Deciphering cellular and molecular determinants of human DPCD protein in complex with RUVBL1/RUVBL2 AAA-ATPases

International audienceDPCD is a protein that may play a role in cilia formation and whose absence leads to primary ciliary dyskinesia (PCD), a rare disease caused by impairment of ciliated cells. Except for high-throughput studies that identified DPCD as a possible RUVBL1 (R1) and RUVBL2 (R2) partner, no in-depth cellular, biochemical, and structural investigation involving DPCD have been reported so far. R1 and R2 proteins are ubiquitous highly conserved AAA+ family ATPases that assemble and mature a plethora of macromolecular complexes and are pivotal in numerous cellular processes, especially by guaranteeing a co-chaperoning function within R2TP or R2TP-like machineries. In the present study, we identified DPCD as a new R1R2 partner in vivo. We show that DPCD interacts directly with R1 and R2 in vitro and in cells. We characterized the physico-chemical properties of DPCD in solution and built a 3D model of DPCD. In addition, we used a variety of orthogonal biophysical techniques including small-angle X-ray scattering, structural mass spectrometry and electron microscopy to assess the molecular determinants of DPCD interaction with R1R2. Interestingly, DPCD disrupts the dodecameric state of R1R2 complex upon binding and this interaction occurs mainly via the DII domains of R1R2