HAL ENVT (Ecole Nationale Vétérinaire de Toulouse)
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Advancing Genotoxicity Assessment by Building a Global AOP Network
No full textInternational audienceABSTRACT Current genotoxicity testing strategies face several challenges, including a high incidence of misleading positive results that lead to unnecessary animal testing, limited mechanistic insights, insufficient integration of innovative methodologies, and a lack of quantitative assessment. Despite rapid advancements in technology and scientific understanding, genotoxicity testing batteries have remained largely unchanged for years. To modernize genotoxicity assessment and incorporate innovative approaches, the development of Integrated Approaches for Testing and Assessment (IATAs) is essential. These frameworks combine existing knowledge with data from New Approach Methodologies (NAMs) aiming to reduce or eliminate reliance on in vivo testing. Genotoxicity is particularly well‐suited for IATA development as numerous cutting‐edge, non‐animal methods have emerged in recent years, including 3D test systems, Prediscreen, MultiFlow, ToxTracker, and transcriptomic‐based biomarkers such as GENOMARK and TGx‐DDI. However, the integration of NAMs into IATAs must be systematic and scientifically robust. In this process, the Adverse Outcome Pathway (AOP) framework plays a crucial role by linking molecular‐level events to adverse health effects, thereby supporting the structured selection of NAMs. This article explores the key challenges and gaps within the current European regulatory frameworks for chemical compound genotoxicity assessment and discusses how an AOP‐based IATA can address these issues. Additionally, we present a global AOP network for permanent DNA damage, designed to guide IATA development and improve regulatory decision‐making. This integrated approach has the potential to enhance the accuracy, efficiency, and ethical standards of genotoxicity assessment while reducing reliance on animal testing
Is there a link between the acute stress response and the movement syndrome of a wild large herbivore?
No full textInternational audienceWhen faced with stressful situations, individuals differ in their behavioural and physiological responses depending on their behavioural type; that is, personality. For mobile organisms, movement is one of the primary responses to threats. Movement syndromes (i.e. suites of correlated movement traits) have been linked to individual differences in risk taking, resource acquisition and performance, and can influence the evolutionary trajectory of these behaviours. Often, standardized tests are used to identify behavioural types; however, behaviours evaluated in controlled settings might not accurately reflect behaviours expressed while free-ranging in the wild. Nonetheless, the acute stress response of an individual expressed during a test could be related to a stress-mitigating behaviour in natural conditions, such as movement. To address this question, we used a long-term monitored population of wild roe deer, Capreolus capreolus, to identify movement-related personality traits and investigate the existence of a movement syndrome. We then examined its link with among-individual differences in the acute stress response (rectal temperature, haematocrit, neutrophil/lymphocyte ratio and docility) expressed during capture and handling. Using GPS monitoring of up to 335 roe deer in a highly heterogenous landscape, we showed that risk-prone individuals (i.e. using riskier habitat and ranging closer to roads during daytime) were also more active, with a lower movement speed and larger home ranges. However, we only found weak support for a link at the among-individual level between an individual's movement syndrome and its stress response during controlled capture, although there was some indication that individuals with an attenuated physiological response to acute stress tended to take more risk when free-ranging. This lack of support might be explained by the fact that different traits reflect different dimensions of the stress response, or by the low number of replicates per individual for these traits. These findings highlight the complexity of interpreting stress responses in natural populations. (c) 2025 The Author(s). Published by Elsevier Ltd on behalf of The Association for the Study of Animal Behaviour
MetagWGS, A comprehensive workflow to analyze metagenomic data using Illumina or PacBio HiFi reads
No full textNational audiencemetagWGS v2.5.
Contribution des outils numériques aux évolutions de l’enseignement vétérinaire : création d’un cas clinique sous forme d’escape game alliant réalité mixte et ateliers de simulation
No full textVeterinary education is evolving toward more interactive and learner-centered approaches, in order to adapt to new generations of students and keep pace with advances in pedagogy. Following an overview of recent pedagogical developments in veterinary training, this thesis focused on the design, implementation, and evaluation of an educational escape game in mixed reality. Centered on the diagnosis of anaplasmosis (Anaplasma phagocytophilum), this serious game combines collaborative puzzles with hands-on simulation workshops. The game was tested by students from the National Veterinary School of Toulouse, and a questionnaire was used to gather their perceptions regarding motivation, memorization, and clinical reasoning. The results highlight a strong interest in the use of immersive environments for experiential learning in veterinary medicine. This work provides a ready-to-use educational tool and illustrates the relevance of escape games as a learning modality. It confirms that integrating digital and immersive tools (virtual reality, mixed reality) together with innovative pedagogical approaches (gamification, serious games) offers major potential to enhance learner engagement and reduce reliance on live animalsL’enseignement vétérinaire évolue vers des approches plus interactives et centrées sur l’apprenant pour s’adapter aux nouvelles générations d’étudiants et suivre les avancées de la pédagogie. Après un état des lieux des évolutions pédagogiques dans la formation vétérinaire, ce travail de thèse s’est attaché à la conception, la réalisation et l’évaluation d’un escape game pédagogique en réalité mixte. Centré sur le diagnostic d’une anaplasmose (Anaplasma phagocytophilum), ce jeu sérieux combine des énigmes collaboratives et des ateliers de simulation technique. Le jeu a été testé par des étudiants de l’École Nationale Vétérinaire de Toulouse et un questionnaire a permis de recueillir leurs perceptions sur la motivation, la mémorisation et le raisonnement clinique. Les résultats mettent en lumière un fort intérêt pour l’usage d’environnements immersifs dans l’apprentissage expérientiel en médecine vétérinaire. Ce travail fournit un outil pédagogique utilisable dès à présent et illustre l’intérêt des escape games comme modalité d’apprentissage. Il confirme que l’intégration d’outils numériques et immersifs (réalité virtuelle, réalité mixte) et de pédagogies innovantes (gamification, jeux sérieux) offre un potentiel majeur pour renforcer l’engagement des apprenants et réduire le recours à l’animal vivant
mineMS2: annotation of spectral libraries with exact fragmentation patterns
No full textInternational audienceIdentification is a major challenge in metabolomics due to the large structural diversity of metabolites. Tandem mass spectrometry is a reference technology for studying the fragmentation of molecules and characterizing their structure. Recent instruments can fragment large amounts of compounds in a single acquisition. The search for similarities within a collection of MS/MS spectra is a powerful approach to facilitate the identification of new metabolites. We propose an innovative de novo strategy for searching for exact fragmentation patterns within collections of MS/MS spectra. This approach is based on (i) a new representation of spectra as graphs of m/z differences, and (ii) an efficient frequent-subgraph mining algorithm. We demonstrate both on a spectral database from standards and on acquisitions in biological matrices that these new fragmentation patterns capture similarities that are not extracted by existing methods, and facilitate the structural interpretation of molecular network components and the elucidation of unknown spectra. The mineMS2 software is publicly available as an R package ( https://github.com/odisce/mineMS2 ). Scientific contribution We present an innovative strategy for structural elucidation, which extracts exact fragmentation patterns of m/z differences within collections of MS/MS spectra. The algorithms are implemented in a software library enabling efficient mining of MS/MS data and coupling to molecular networks. We show on real datasets the specific value of the patterns as fragmentation graphs for structural interpretation and de novo identification, and their complementarity to existing approaches
Une multitude de déterminismes génétiques et de mécanismes moléculaires pour comprendre les liens génome-phénome
No full text1.1. Contexte scientifique et problématiques 1.1.1. L'EGP : un modèle multi-échelle de régulations épigénétiques sous déterminisme génétique 1.1.2. L'EGP : un modèle de mécanismes évolutifs différenciés entre espèces 1.1.3. L'EGP : un modèle pour évaluer les effets parentaux dans la variabilité des caractères complexes 1.2. L'EGP à l'ère du multi-omiques, de la science ouverte et de l'IA -quels apports par et pour les espèces d'élevage ? 1.2.1. Axe 1 -Réseaux d'interactions multi-échelles des gènes soumis à empreinte 1.2.2. Axe 2 -Mécanismes évolutifs des gène soumis à empreinte 1.2.3. Axe 3 -Contribution des effets parentaux dans les liens génome-phénome REFERENCES BIBLIOGRAPHIQUES CURRICULUM VITAE LISTE DES PRODUCTION
L’ ovariectomie de la chienne par cœlioscopie : Actualités Bibliographiques
No full textLaparoscopic sterilisation of the dog, known as minimally invasive surgery, is increasingly being performed. This thesis presents recent technological advances regarding instruments (single port, thermofusion forceps, etc.), insufflation equipment and visualisation. These technological advances have repercussions on surgical techniques: cannula placement, handling of the ovary, haemostasis techniques, etc.The main advantages of laparoscopy lie in the post-operative comfort of the animals, the aesthetics of the scars and the possibility of combining it with gastropexy. Nevertheless, this technique requires a learning curve, specific training and a suitable technical environment. Laparoscopy represents a substantial investment, which can be recouped by diversifying the range of procedures: biopsies, ectopic testicles, arthroscopies, etc. The veterinary surgeon will be able to offer innovative non-invasive techniquesLa stérilisation chez la chienne par la cœlioscopie, dite chirurgie mini-invasive, est de plus en plus réalisée. La thèse présente les avancées technologiques récentes en termes d’instruments (port unique, pinces à thermofusion, …), de matériel d’insufflation et de visualisation. Ces avancées technologiques ont des répercussions sur les techniques chirurgicales : mise en place des canules, maniement de l’ovaire, technique d’hémostase, … Les principaux avantages de la cœlioscopie résident dans le confort post-opératoire des animaux, l’esthétique des cicatrices et la possible association à une gastropexie. Néanmoins, cette technique impose une courbe d’apprentissage, une formation spécifique et un environnement technique adapté. La cœlioscopie représente un investissement conséquent qui pourra être rentabilisée grâce à la diversification des interventions : biopsies, testicules ectopiques, arthroscopies … Le praticien vétérinaire pourra proposer des techniques innovantes non invasives
Mobile genetic elements in Staphylococcus aureus, vectors of antibiotic resistance
No full textInternational audienceStaphylococcus aureus, a significant human and animal pathogen, exhibits remarkable capacity for antibiotic resistance development. This is closely linked to its acquisition of antibiotic resistance genes (ARGs) through mobile genetic elements (MGEs), constituting 15-20% of its genome. ARGs in S. aureus spread through highly successful epidemic clones but also via horizontal transfer through MGEs. The associations between ARGs and MGEs are still underexplored in S. aureus. Yet, horizontal gene transfer appears to play a crucial role in the emergence of multidrug-resistant clones, posing a major threat to human and animal health. A large-scale comparative genomic study was conducted to explore the associations between the resistome (set of ARGs) and the mobilome (set of MGEs) of over 10,000 S. aureus genomes of human and animal origin available in the NCBI database. To obtain a more precise and dynamic view of an ARG-rich elements, the plasmid content and their associated antibiotic resistance genes in S. aureus strains isolated from animals were characterized using long-read sequencing. These strains were collected through the French surveillance network, Resapath. Our analyses revealed a wide diversity of MGEs and ARGs in S. aureus, with plasmids and transposons being the main vectors of resistance genes. Numerous plasmid/ARG associations were identified, suggesting that these MGEs play a crucial role in the dissemination of resistance. The prevalence of certain families of ARG-carrying plasmids is similar in strains of both human and animal origin, highlighting their dissemination potential independently of the host. Furthermore, plasmids and their associated ARGs can propagate across different sequence types (ST). The high variability of plasmid/ARG associations within a single ST and their spread between STs underline the critical role of these MGEs in shaping the resistome of S. aureus. Our studies provide valuable insights into the complex interactions between MGEs and ARGs in S. aureus. Plasmids serve as the main reservoir of antibiotic resistance genes and, as such, drive the evolution and adaptation of various clones under selective environments. These findings underscore the need to elucidate the mechanisms underlying their epidemic success
Enhancing cognitive functions in aged dogs and cats: a systematic review of enriched diets and nutraceuticals
No full textInternational audienceWith advancements in veterinary care and the growing recognition of pets as integral member of the family, the lifespans of dogs and cats have significantly increased, leading to a higher prevalence of age-related conditions, including cognitive dysfunction syndrome (CDS). CDS adversely impacts pets' quality of life and presents emotional and practical challenges for owners. Given its similarities to Alzheimer's disease in humans, CDS has gained attention as a target for nutrition-based interventions aimed at preserving cognitive function. This systematic review evaluates the efficacy of enriched diets and nutraceuticals in improving cognition in aging companion animals. A literature search was conducted using PubMed, CAB Abstracts, Web of Science, and Dimensions to identify clinical trials published in English that investigated the effects of enriched diets or nutraceuticals on cognitive functions in aged cats or dogs. Study quality was assessed using a modified CAMARADES checklist. A total of 30 studies (27 canine and 2 feline trials) published between 2002 and 2023 were reviewed. Studies on enriched diets generally demonstrated higher methodological quality compared to those on supplements. Omega-3 fatty acids showed cognitive benefits in aging pets, especially at higher doses, while antioxidants from plant extracts and products and vitamins E and C alone were less effective but remain essential for stabilizing omega-3 fatty acids. Other supplements, including S-adenosyl methionine, medium-chain triglycerides, homotaurine, and apoaequorin, also showed promise. However, future studies must standardize protocols, include robust control groups, and utilize both objective tasks and subjective questionnaires to strengthen conclusions
Sphingomyelins in mosquito saliva modify the host lipidome to enhance transmission of flaviviruses by promoting viral protein levels
No full textMosquito saliva plays a determining role in flavivirus transmission. Here, we discover and elucidate how salivary lipids enhance transmission. Building upon our discovery of salivary extracellular vesicles (EV), we determined that lipids within mosquito EVs, and neither within human EVs nor virions, enhance infection for flaviviruses in primary cell types relevant for transmission. Mechanistically, mosquito EV-lipids specifically promote viral protein levels by reducing ER-associated degradation. Infection enhancement is caused by sphingomyelins within mosquito salivary EVs that elevate sphingomyelin concentration within host cells. Transmission assays showed that mosquito EV-lipids exacerbate disease severity. Our study reveals that EV-associated sphingomyelins within mosquito saliva enhance transmission for multiple flaviviruses by reconfiguring the host lipidome to promote viral protein levels and the resulting skin infection. Our findings open a new dimension centered on lipids in the interplay between hosts, mosquitoes and flaviviruses that determine transmission, unveiling lipids as a new pan-flavivirus target. Highlights Lipids within mosquito extracellular vesicles (EVs) enhance infection in primary skin and immune cells for multiple flaviviruses. Mosquito EV-lipids increase flaviviral protein levels by dampening ER-associated degradation. Sphingomyelins within salivary EVs are responsible for the infection enhancement by altering host lipidome. Co-injection of mosquito EV-lipids exacerbate disease severity