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Identification of Candidate Biomarkers Detected in the Urine of Racehorses After Anabolic Agent Administration: Use of Orthogonal Methods for Structural Elucidation
No full textInternational audienceABSTRACT Biomarker identification by mass spectrometry represents a key step in the workflow of nontargeted metabolomic studies. Given the complexity of the data, this step, which must be carried out by a trained specialist, is time‐consuming, and the biomarkers discovered are not always identified. While this stage is not an obstacle to the development of new screening and classification tools, it is nonetheless crucial to a better understanding of the results obtained. For this reason, the aim of this study was to perform structural elucidation of candidate biomarkers, which had previously been displayed to screen for the administration of anabolic agents in the urine of racehorses and whose robustness had been evaluated. The present study involved a combination of various analytical strategies, including enzymatic hydrolysis, high‐resolution mass spectrometry and ion mobility (LC‐HRMS, LC‐IMS‐HRMS), and in vitro experiments. Two candidate biomarkers were identified as phase II metabolites of tebuconazole, belonging to the equine exposome. This identification opens the way to further investigations into the relationship between the presence of this compound and its disruption in horse urine following anabolic agent administration. Overall, the use of orthogonal approaches provided better complementary information on the structure of the compound and ultimately enabled us to identify biomarkers with the highest possible level of confidence
Sphingolipids in Extracellular Vesicles Released From the Skeletal Muscle Plasma Membrane Control Muscle Stem Cell Fate During Muscle Regeneration
No full textInternational audienceExtracellular vesicles (EVs) represent a cytokine-independent pathway though which skeletal muscle (SkM) cells influence the fate of neighbouring cells, thereby regulating SkM metabolic homeostasis and regeneration. Although SkM-EVs are increasingly being explored as a therapeutic strategy to enhance muscle regeneration or to induce the myogenic differentiation of induced pluripotent stem cells (iPSCs), the mechanisms governing their release from muscle cells remain poorly described. Moreover, because muscle regeneration involves a tightly regulated inflammatory response it also important to determine how inflammation alters SkM-EV cargo and function in order to design more effective EV-based therapies. To address this knowledge gap, we isolated and characterized the large and small EVs (lEVs, sEVs) released from SkM cells under basal conditions and in response to TNF-α, a well-established inflammatory mediator elevated in both acute muscle injury and chronic inflammatory conditions such as type 2 diabetes. We then evaluated the regenerative roles of these EV subtypes in vivo using a mouse model of cardiotoxin-induced muscle injury, with a specific focus on their bioactive sphingolipid content. Using transmission, scanning or cryo-electron microscopy, lipidomic profiling and an adenoviral construct to express labelled CD63 in myotubes, we demonstrated that SkM cells release both sEVs and lEVs primarily from the plasma membrane. Notably, sEVs were generated from specialized membrane folds enriched in the EV markers ALIX (ALG-2 interacting protein X) and TSG101, as well as lipid raft-associated lipids. During regeneration, sEVs promoted M1 macrophage polarization and migration and muscle stem cell (MuSC) differentiation, thereby accelerating muscle repair. In contrast, lEVs inhibited and promoted MuSC proliferation and impaired the transition from the pro-inflammatory to the anti-inflammatory response, an essential step for promoting MuSC differentiation. Treatment of isolated muscle fibres with SkM-EVs revealed that the distinct effects of sEVs and lEVs on MuSC behaviour and macrophage phenotype could be largely explained by differences in their lipid composition, particularly the ratio of sphingosine-1-phosphate (S1P) subspecies. However, TNF-α exposure altered these ratios in sEVs and impaired their regenerative functions on MuSC and their effect on macrophage migration and polarization. These results demonstrate for the first time the importance of the sphingolipid content of EVs released by skeletal muscle in their regenerative function within muscle tissue, largely explained by their role as carriers of different subspecies of sphingosine-1-phosphate. This suggests that modulating the sphingolipid composition of EVs could be a viable strategy to enhance the regenerative potential of muscle tissue in addition to therapeutic interventions
Développement et validation d'un outil pédagogique dans le cadre de l'interprétation des radiographies osseuses chez les carnivores domestiques
No full textThe aim of this study is to create and validate an educational quiz on bone radiography in domestic carnivores, with the aim of providing veterinary students with additional teaching support. This tool is designed to reinforce their radiographic analysis skills through the use of didactic clinical cases of the main bone diseases. A comparative study was carried out to measure the impact of the quizzes on memorization. The results showed an overall positive assessment of the tool by the students, combined with a significant improvement in scores. This system highlights the value of diversifying teaching aids, particularly in the context of developing online training.L’objet de cette étude est la création et la validation d’un quiz pédagogique en radiographie osseuse chez les carnivores domestiques avec pour objectif de fournir un support supplémentaire à l’enseignement des étudiants vétérinaires. Cet outil permet de renforcer leur capacité d’analyse radiographique grâce à l’utilisation de cas cliniques didactiques des principales maladies osseuses. Une étude comparative a été menée pour mesurer l'impact des quiz sur la mémorisation. Les résultats montrent une appréciation globale positive de l’outil par les étudiants associée à une amélioration significative des scores. Ce dispositif met en évidence l’intérêt de diversifier les supports pédagogiques, notamment dans le cadre du développement de la formation en ligne
Le pyomètre chez la chatte : étude rétrospective de l’épidémiologie, la présentation clinique et la prise en charge à partir d’une série de cas reçus au CHUV d’Oniris et parmi les cliniques vétérinaires de Loire-Atlantique et de Bretagne
No full textLe pyomètre est une affection utérine grave, caractérisée par une accumulation purulente dans la lumière utérine, survenant principalement en phase lutéale. Bien documentée chez la chienne, cette pathologie reste encore peu étudiée chez la chatte, notamment en raison de sa prévalence plus faible, conséquence directe du taux élevé de stérilisation dans cette espèce. Cette thèse a pour objectif de proposer une synthèse des connaissances actuelles sur le pyomètre félin et de les compléter par une étude rétrospective complète, menée à partir d'une centaine de cas diagnostiqués au CHUV d'Oniris entre 2002 et 2024 et dans les cliniques vétérinaires de Bretagne et de Loire-Atlantique en 2024. L'analyse des données recueillies a permis de dégager des tendances épidémiologiques (âge moyen au diagnostic de 6,5 ans, majorité de chattes nullipares, non stérilisées, vivant en intérieur, et exposition fréquente à une contraception hormonale), cliniques (pertes vulvaires, abattement, anorexie, hyperthermie), biologiques (leucocytose neutrophilique, hyperlactatémie, hypercréatininémie, dilatation des cornes utérines visualisée à l'examen échographique) et thérapeutiques. Le traitement chirurgical par ovario-hystérectomie a été majoritaire et associé à un bon pronostic. Ce travail souligne une cohérence globale entre les résultats obtenus et les données de la littérature, et appelle à développer des études prospectives dédiées à cette affectation chez le chat, afin d'en améliorer la détection et la prise en charge
The PHARAON project: new bases for a transverse standard to assess indoor air mitigation
No full textInternational audienceThe indoor air treatment market has evolved significantly over the past 10 years, moving from treatment to remediation. Performance criteria have to be reconsidered to face the diversification of technologies (active or passive; destructive or not) and the evolutions of practices Are existing evaluation protocols still suitable? Actually, they do not allow the assessment and comparison of any commercial remediation solutions and do not integrate the diversity of pollutants of indoor environments. To make public authorities and consumers aware, it is necessary: (i) to quantify the performances of any remediation solution, whatever the technology, (ii) to compare the devices between them, and regarding air renewal rate, and (iii) to align the effective contribution to IAQ where they are placed and whatever the remediation approach.The PHARAON project has been launched in France in 2023 with the support of French Environmental Agency. It promotes a transdisciplinary approach to provide an integrative evaluation protocol of remediation solutions. The final goal of that project is to move forward and unify air treatment standards. The innovation point of this work relies in the fact that the experimental protocol will apply to standalone device as well as sorptive walls, or ventilation and airing. This work aims at presenting the first three aspects of the project: (i) definition and justification of model pollutants of interest including gas, particulate matter and biological aerosol, (ii) description of a typical pollution scenario, and (iii) introduction of metrics of interest to assess the performance of remediation solutions
Des agents pathogènes, des tiques, des hôtes et des climats. Une vision One Health
No full textInternational audienc
Comparative impact of porcine reproductive and respiratory virus and swine influenza A virus infections on respiratory lymph nodes B cells and macrophages
No full textInternational audiencePorcine Reproductive and Respiratory Syndrome Virus (PRRSV) persists as a major challenge in swine production due to its capacity for long-term persistence and immune evasion. PRRSV delays the onset of neutralizing antibodies, a phenomenon that significantly contributes to its chronicity. Utilizing advanced methodologies to analyze the porcine inverted lymph node (LN), this study provides a comparative analysis of B cell maturation in PRRSV-1 infection and acute swine influenza A virus infection. Key PRRSV-specific immune evasion mechanisms were identified, including the expression of PD-L1 in efferent macrophages, the induction of extrafollicular plasmocytes, and the recruitment of inflammatory monocytes/macrophages. Parallel findings in PRRSV-2 suggest the generalization of these mechanisms across PRRSV strains. Intriguingly, these immune evasion strategies share similarities with those employed by human immunodeficiency virus (HIV) and murine chronic lymphocytic choriomeningitis virus (LCMV). These insights open new avenues forthe design of improved vaccines targeting PRRSV and related viruses
Optimisation numérique du stockage d’énergie par adsorption de CO₂ comprimé : Modélisation des transferts de chaleur et de masse
No full textInternational audienceLe stockage d’électricité hors réseau est un enjeu crucial pour l’intégration des énergies renouvelables, en particulier dans les régions isolées ou à faible accès aux infrastructures électriques. Cette étude propose une solution innovante basée sur le stockage par compression de CO₂, amélioré par adsorption sur des matériaux nanoporeux. Ce procédé permet d’augmenter significativement la densité énergétique du stockage tout en minimisant les pertes thermiques associées à la détente du gaz.L’intelligence numérique intervient à plusieurs niveaux pour optimiser le système : modélisation thermodynamique, simulation des transferts de chaleur et de masse dans le réservoir, ainsi qu’analyse des performances en fonction des conditions de charge et de décharge. Grâce à ces outils, il devient possible d’optimiser la conception des réservoirs et des matériaux adsorbants, réduisant ainsi les coûts et augmentant l’efficacité du stockage.Cette approche s’inscrit dans une perspective de transition énergétique durable, en proposant une alternative performante aux solutions existantes et en contribuant à la réduction des émissions de gaz à effet de serre par une meilleure gestion de l’énergie
Innover pour la santé animale au travers de l’intelligence artificielle à finalité prédictible – Applications aux maladies respiratoires des jeunes bovins
No full textEffective management of infectious diseases in livestock requires detecting and forecasting outbreaks despite the complexity of host–pathogen–environment interactions and the difficulty of extracting relevant information from farm sensors. This thesis proposes an innovative approach that directly couples sensor data with knowledge derived from mechanistic epidemiological modeling. By combining deep learning, which can automatically extract patterns from complex signals, with mechanistic models based on veterinary expertise, we aim to improve both short-term diagnosis and longterm disease predictions in livestock. The main contributions of this work are: (1) coupling empiricalsensor data with mechanistic simulations to fill the gap between sensor-based observations and theoretical knowledge; (2) explicitly incorporating uncertainty into predictions to enhance reliability; and (3) developing a method to differentiate pathogen-specific scenarios to guide targeted interventions. Applied to respiratory diseases in young cattle (BRD), our methods have demonstrated, under both real and simulated conditions, their ability to automate shortterm diagnosis and long-term predictions BRD dynamics, thereby significantly reducing antibiotic use and improving farm performance. This work opens new perspectives by proposing a modular methodology that combines sensor data and knowledge, potentially serving as an innovative decision-support tool for optimized health management.La gestion des maladies infectieuses en élevage nécessite de détecter et prévoir les épidémies malgré la complexité des interactions hôte-pathogène-environnement et la difficulté d'extraire des informations pertinentes à partir des capteurs en élevage. Cette thèse propose une approche innovante qui associe directement les données des capteurs à des connaissances issues de la modélisation épidémiologique mécaniste. En combinant l’apprentissage profond, capable d’extraire automatiquement des motifs dans des signaux complexes, et des modèles mécanistes reposant sur l’expertise vétérinaire, nous visons à améliorer le diagnostic à court terme et les prévisions à long termedes maladies en élevage. Les contributions principales de ce travail sont : (1) la fusion des données empiriques d’un capteur avec des simulations mécanistes, tirant parti des observations et des savoirs théoriques ; (2) l’intégration explicite de l’incertitude dans les prédictions pour en renforcer la fiabilité ; et (3) le développement d’une méthode de différenciation des scénarios pathogéniques afin d’orienter des interventions ciblées. Appliquées aux maladies respiratoires des jeunes bovins (BRD), nos méthodes ont démontré, en conditions réelles et simulées, leur capacité à automatiser le diagnostic et à prévoir l’évolution de la maladie, ouvrant ainsi la voie à une réduction significative de l’utilisation d’antibiotiques et à une amélioration des performances des élevages. Ce travail ouvre de nouvelles perspectives en proposant une méthodologie modulaire alliant capteurs et connaissance, susceptible de constituer un outil de décision innovant pour une gestion sanitaire optimisée
Building thermal control: Hierarchical design from limited data using gray-box or black-box internal models for model predictive control
No full textInternational audienceThis paper presents a hierarchical model predictive control (MPC) framework designed to accommodate the diversity of heating equipment in building energy systems. The proposed architecture consists of a supervisory MPC for power planning and tracking controllers for device-level regulation. The framework systematically compares grey-box system identification, using an equivalent Resistance-Capacitance (RC) model, against black-box Subspace State Space Identification (4SID), evaluating their performance with limited datasets. At the tracking level, Virtual Reference Feedback Tuning (VRFT) offers a model-free approach to equipment control, eliminating the need for a detailed Heating, Ventilation, Air Conditioning system model. The proposed approach is validated using a multi-zone residential test case from the Building Optimization Testing Framework. Results show that although both models achieve similar open-loop prediction accuracy, their performance diverges under closed-loop control. Under different weighting configurations, the proposed scheme using the RC model achieves approximately a 3-12% reduction in energy consumption while maintaining comparable or even lower levels of thermal discomfort compared to the blackbox 4SID model. The study concludes with a discussion of practical considerations and the potential for broader deployment