HAL ENVT (Ecole Nationale Vétérinaire de Toulouse)
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Estimating flux dynamics from metabolite concentration time courses with dynafluxr
No full textMotivation: Quantifying metabolic fluxes and their dynamics is crucial for addressing fundamental and applied questions in systems and synthetic biology, health, and biotechnology. Since metabolic fluxes are not directly observable, they must be estimated using model-based approaches. While several methods are available to quantify steady-state fluxes, approaches for quantifying flux dynamics remain limited.Results: We present a method to quantify flux dynamics from metabolite concentration time courses. Our approach employs constrained B-splines to solve mass balance equations without requiring prior knowledge of catalytic or regulatory mechanisms, or enzymatic parameters. We provide a comprehensive mathematical framework for dynamic flux calculation and demonstrate that our method enables accurate and robust quantification of flux dynamics for both simulated and experimental datasets.</p
Bovine Lymphocyte Intestinal Retention Defect (BLIRD): a novel recessive immunogenetic disorder in Holstein cattle
No full textInternational audienceDozens of missed recessive loci affecting homozygous carriers' life expectancy were recently reported. This article details the clinical, biological and pathological manifestations of a new bovine genetic disorder caused by the ITGB7 p.G375S point mutation in the French Holstein cattle breed (BLIRD: OMIA:002872-9913). Our thorough study involved database analysis of genotyped cattle and a series of case-control investigations of forty individuals homozygous for the causative variant. These variant homozygotes had a significantly shorter lifespan (fewer than 64% surviving past three years vs. 87% in control), along with reduced body weight, daily weight gain, and dairy performance. The mutation did not affect most biochemical parameters, but a marked lymphocytic leucocytosis, moderate eosinophilia and differences in faecal microbiota were observed. Although non-pathognomonic symptoms may be confused with those of common environmental diseases, the blood profile effectively identified suspected carriers who developed ill-thrift and poor growth as heifers. Our research demonstrates that the bovine ITGB7 p.G375S substitution leads to reduced longevity, poor condition and production in most homozygous carriers. Furthermore, this spontaneous model may help to refine the functions of the integrin β7 (ITGB7) in immune homeostasis and defence
Bioinspired Lipids as Leads for Developing New Anti-TB agents with a Unique Mechanism of Action
No full textInternational audienc
Genomic findings with familial implications: agenda setting in light of mainstreaming
No full textInternational audienceAn international workshop was held in Leuven, Belgium, on June 19–20, 2023, to discuss the communication of genetic risk information within families in the context of personalized prevention. Organized as part of the Horizon Europe project PROPHET (PeRsOnalised Prevention roadmap for the future HEalThcare in Europe), the event gathered interdisciplinary stakeholders to explore the benefits and challenges of various policy approaches for returning genetic test results with implications for family members. Five key themes emerged from the discussions: (1) recognizing family communication as an ongoing process, (2) adopting a family-centered approach rather than an individual one, (3) clarifying roles and responsibilities in the communication process, (4) addressing the lack of clear guidelines and policies, and (5) ensuring sufficient resources. To enhance family communication of genetic risk information, participants emphasized the importance of improving pre-test counseling and follow-up procedures, implementing policies to clarify roles and responsibilities, and providing training for healthcare professionals both within and outside genetic services
A selective bottleneck during host entry drives the evolution of new plant symbionts
No full textInternational audienceThe acquisition of mobile genetic elements (MGEs) can trigger radical shifts in microbial lifestyles, for example by converting a mutualist into a pathogen or vice versa. These transitions often involve changes in host range, infection strategies, or ecological niches, which typically require specific adaptations to the different stages of the new life cycle. While comparative genomic studies have documented several MGE-associated lifestyle transitions, a detailed understanding of the tempo and mode of adaptation to new symbiotic lifestyles is still lacking.Here, we sought to evolve new nitrogen-fixing bacterial symbionts of the legume plant Mimosa pudica from an ancestral plant pathogenic bacterium, Ralstonia solanacearum, which was engineered with a plasmid carrying essential symbiosis genes. We experimentally evolved this strain for over 900 generations during serial passages through a simplified symbiotic life cycle (comprising rhizosphere inoculation, root entry, and within-plant proliferation) and characterized the dynamics of molecular and phenotypic adaptation in the evolved populations.Multiple independent lineages exhibited rapid and parallel fitness increase during their interaction with M. pudica. Whole-population sequencing revealed a continuous accumulation of mutations, facilitated by a plasmid-induced transient hypermutagenesis phase before host entry. We observed sequential sweeps of mutational cohorts, with multiple adaptive mutations co-occurring within these cohorts. Notably, all adaptive mutations enhanced host entry, while only a subset also improved within-host proliferation. Computational modelling suggests that this pattern is a consequence of the strong selective bottleneck occurring at host entry and immediately following the hypermutagenesis phase. Our findings highlight how selective bottlenecks shape adaptive trajectories of symbiotic bacteria experiencing complex infection processes
Activité anti-influenza des protéines interféron-induites Mx1 d'espèces domestiques
No full textHighly pathogenic avian H5N1 influenza A viruses (IAV) circulating since 2020, have expanded their host range to include new domestic mammals, raising concerns that these species may facilitate adaptation to humans. This process could involve escape from the interferon-induced restriction factor Mx1 through selection of mutations in the viral nucleoprotein (NP). We compared the anti-IAV activity of Mx1 proteins from human (huMx1), swine (swMx1), bovine (bovMx1), and American mink (minkMx1). bovMx1 is more active than swMx1 and comparable to huMx1 against a swine avian-like virus, while minkMx1 shows no activity. Some NP mutations confer resistance to huMx1 and bovMx1 without impairing viral replication, whereas others severely reduce viral fitness depending on genetic background, revealing strong epistatic interactions. Lastly, we developed experimental tools for NP mutational screening, based on HA-defective recombinant viruses and transcomplementing cell lines stably expressing Mx1.Les virus influenza A (VIA) aviaires H5N1 hautement pathogènes circulant depuis 2020 ont élargi leur spectre d’hôte à de nouveaux mammifères domestiques, laissant craindre une adaptation facilitée à l’Homme. Celle-ci pourrait passer par un échappement au facteur de restriction interféron-induit Mx1, via la sélection de mutations sur la nucléoprotéine virale (NP). Nous avons comparé l’activité anti-VIA des Mx1 humaine (huMx1), porcine (swMx1), bovine (bovMx1) et du vison d’Amérique (minkMx1). bovMx1 est plus active que swMx1 et similaire à huMx1 contre un virus porcin d’origine aviaire, tandis que minkMx1 est inactive. Certaines mutations de la NP confèrent une résistance aux Mx1 sans coût réplicatif, tandis que d'autres compromettent la viabilité virale, révélant de fortes interactions épistatiques. Enfin, nous avons établi des outils adaptés en vue d’un criblage mutationnel de la NP, basés sur un système virus défectifs - cellules transcomplémentantes exprimant stablement Mx1
IMAGE001 : A new livestock multispecies SNP array to characterize genomic variation in European livestock gene bank collections
No full textInternational audienceAbstract Molecular genetic characterization of genetic resources is essential to study biodiversity. Whereas whole genome sequencing is still relatively expensive, low density SNP arrays offer a cost‐effective and standardized solution. However, most of the current arrays are species specific. Their high SNP density often exceeds diversity mapping requirements and remains too costly for many genetic resource managers. The IMAGE H2020 project aimed at developing a low‐cost multispecies SNP array to facilitate mapping of the genetic diversity in samples stored in gene banks and in vivo (on farm) traditional populations. This farm animal multispecies array contains approximately 10 K SNPs per species. The species included are cattle, sheep, goat, horse, pig, and chicken. We developed and tested this array on many samples from each of the six species. We describe here the SNP coverage and informativity across 253 breeds. We show that the array can be used to cluster local breeds according to history and genetic diversity. We illustrate its use for parentage testing. The array is publicly available at a reasonable price if ordered in multiples of 384 samples, leading to an overall cost of genotyping of approximately 15 euros per sample
Création d’un jeu pédagogique comme outil d’aide à l’apprentissage de la Parasitologie du chien et du chat
No full textPedagogical approaches are constantly evolving, as are the educational tools available to instructors, with the aim of better supporting students in their learning processes. Serious games represent a promising avenue for enhancing student support. This thesis project aligns with this approach and presents the development of an interactive educational game created using the Genially® platform. The game features five clinical cases focused on parasitic and vector-borne diseases commonly encountered in dogs and cats: flea infestation, sarcoptic mange, ringworm, babesiosis, and leishmaniosis. Incorporating the principles of active learning, this tool was proposed to third-year students at the National Veterinary School of Toulouse and received highly positive feedbacks. It thus highlights the relevance of combining digital tools with traditional teaching methods in veterinary education, in order to facilitate the comprehension and memorization of complex concepts by veterinary students.La pédagogie évolue constamment, tout comme les outils pédagogiques mis à disposition des enseignants, afin d’accompagner au mieux les étudiants dans leurs apprentissages. L’usage de jeux sérieux constitue une piste prometteuse pour l’amélioration de l’accompagnement des étudiants. Ce travail de thèse s’inscrit dans cette dynamique et présente la création d’un jeu pédagogique interactif développé sur la plateforme Genially®. Il propose cinq cas cliniques centrés sur des ectoparasitoses et maladies vectorielles fréquemment rencontrées chez le chien et le chat : la pulicose, la gale sarcoptique, la teigne, la piroplasmose et la leishmaniose. Cet outil intégrant les principes de la pédagogie active a été soumis aux étudiants de troisième année à l’École Nationale Vétérinaire de Toulouse et a reçu un accueil très favorable. Il illustre donc l'intérêt d'associer les outils numériques aux formats traditionnels dans l’enseignement de la médecine vétérinaire, afin de faciliter la compréhension et la mémorisation de notions complexes par les étudiants vétérinaires
Editorial: Ulcerative Colitis Management in the Biologic Era—Data From the English Healthcare Databases
No full textInternational audienc
The Gascon pork sector
No full textInternational audienceIn 2017, the Gascon pork sector obtained two Protected Designations of Origin (PDO): one for carcasses and one for dry-cured hams. The specifications stipulate that the animals must be reared in the open air in a defined area of the central Pyrenees at an altitude of between 150 and 1,000 metres. They are slaughtered between 12 and 24 months old.One of the aims of this research project is to investigate the existence of a terroir effect likely to influence the biochemical, nutritional and organoleptic characteristics of PDO Noir de Bigorre hams.To achieve this, a quantitative descriptive analysis and a pivot©profile were carried out on dry-cured hams from three different zones of the PDO's geographical area: the Pyrenean foothills, the hillsides and the south of the Gers County. The hams were assessed according to 26 descriptors developed in focus groups by a trained internal panel of 12 subjects. At the same time, the analytic profiles of glycerides, fatty acids and amino acids of the dry-cured hams were carried out.Nine descriptors were found to discriminate between hams, five of which highlighted particularities in rearing and feeding before slaughter, specifically for hams from the hillsides and Pyrenean foothills. Differences were noted in the appearance of the fat, lean and texture of the cured hams which were sustained by the results of the pivot©profile. Chemical analyses of the composition of subcutaneous and intramuscular fats in relation to the organoleptic results of the same hams complete these observations