HAL ENVT (Ecole Nationale Vétérinaire de Toulouse)
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Ethics of Personalised Medicine: Importance of the Multidisciplinary Approach in KidneySign Project
No full textInternational audienceABSTRACT This article explores the ethical and societal issues in developing personalised medicine (PM) as part of the KidneySign project, which aims to mobilise translational big data to validate a proteomic signature of renal fibrosis with prognostic value. This research offers hope for improved management of chronic kidney disease, including diagnosis and treatment. This article examines how the human and social sciences can be mobilised within a biomedical research project to identify and prevent concomitant ethical, legal and social issues. This point of view defends a multidisciplinary approach to PM and artificial intelligence in medicine. Presenting theoretical and methodological contributions of social sciences in the case of KidneySign offers an opportunity to better understand the integration of these disciplines in biomedical research. It allows us to question the study protocol itself and to frame it through legal obligations, as well as potential legal consequences and challenges. Moreover, sociological assessments help identify key points and highlight the limits of the technophilic fantasy in the representations of patients and health professionals. The introduction of new technologies into medical research and practice requires special attention to ethics
CAGES OU PARCS AVEC JARDIN d'HIVER : EFFET DES CONDITIONS DE LOGEMENT SUR LE COMPORTEMENT, LE STRESS ET LES PERFORMANCES DE LAPINS EN CROISSANCE
No full textInternational audienceCages vs courtyard: effect of the housing conditions on behaviour, stress and performance of growing rabbits. Rabbit welfare is a concern for society. It is strongly influenced by living conditions. We compared the welfare (behaviour and stress), growth and viability of 60 rabbits (♀ Hycole x ♂ PS119 Hypharm), reared in two different housing conditions from 38 (weaning) to 70 days: standard dual-purpose cages (Cage group) versus pen with a winter garden (Courtyard group). The growth was higher in Courtyard group (2.75kg vs 2.46kg at 70 days, P < 0.01), the viability was similar for both housing conditions (97% vs 97.5%, NS). The hair corticosterone levels at 70 days tended to be higher in Courtyard group than in Cage group (2.48 vs 1.76 pg/mg hair, P= 0.08). In the Courtyard group, rabbits were more active and expressed more exploration behaviours (walking; running; rearing) and more grooming behaviours while in the Cage group, rabbits rested more and had more contact interactions (P < 0.05). Access to a courtyard gave the rabbits a larger behavioural repertoire. In conclusion, the present results showed that access to a courtyard could be a good solution to improve rabbit welfare, by diversifying the behavioural repertoire and increasing growth without increasing stress or reducing animal viability.La société est préoccupée par le bien-être des lapins de chair qui est fortement influencé par les conditions de vie. Des systèmes alternatifs se développent, mais leurs effets sur le bien-être animal doivent être objectivés. Nous avons comparé certaines composantes essentielles du bien-être (comportement et stress), et les performances zootechniques (croissance et survie) de 60 lapins (♀ Hycole x ♂ PS119 Hypharm), élevés dans deux conditions de logement différentes de 38 (sevrage) à 70 jours : cages standard polyvalentes (groupe Cage) versus parcs avec jardin d'hiver (groupe Parc). Les animaux ont été pesés à 37 et à 70 jours. Le comportement a été mesuré par scan sampling à 48 et 70 jours d'âge selon un éthogramme défini (18 comportements et 5 catégories : locomotion, entretien, confort, exploration et interactions sociales). La corticostérone a été dosée dans le poil à 70j par une méthode Elisa en immunocompétition. Le poids des lapins à 70 jours a été plus élevé dans le groupe Parc (2,75 kg contre 2,46 kg, P < 0,01), tandis que la survie entre 38 et 70 jours a été similaire pour les deux conditions de logement (97 % contre 97,5 %, NS). Les niveaux de corticostérone dans les poils à 70 jours ont eu tendance à être plus élevés dans le groupe Parc que dans le groupe Cage (2,48 vs 1,76 pg/mg de poils, P= 0,08), mais reste dans l'intervalle des valeurs de référence décrites chez le lapin en croissance. Dans le groupe Parc, les lapins ont été plus actifs et ont exprimé plus de comportements d'exploration et de locomotion (marcher, courir, se dresser) et plus de comportements de toilettage alors que dans le groupe Cage, les lapins se sont plus reposés et ont eu plus d'interactions de contact (P < 0.05). Le système parcs avec accès à un jardin d'hiver a permis aux lapins d'avoir un répertoire comportemental plus riche. En conclusion, les présents résultats montrent que l'accès à un jardin d'hiver pourrait être une bonne solution pour améliorer le bien-être des lapins, en diversifiant le répertoire comportemental et en augmentant la croissance sans augmenter le stress ou réduire la viabilité des animaux
Detection of genomic regions affecting thermotolerance traits in growing pigs during acute and chronic heat stress
No full textInternational audienceThis study aimed to identify genomic regions involved in animal responses to chronic and acute Heat challenges in 1149 pigs tested in three climatic environments (temperate, tropical, and temperate Heated to 30 °C for 3 weeks). Production (growth rate, feed intake and efficiency, backfat thicknesses) and thermoregulation (rectal and cutaneous temperatures) traits were recorded in a backcross between Large White and Créole pigs. Genome-wide association studies were applied to the full population assuming SNP effects to be the same in both environments or to depend on the environment (GxE), and to the population in each environment separately. The genetic models used linkage disequilibrium in all chromosomes (LD) or only in Large White chromosomes (LW), or breed-of-origin of F1 alleles through linkage analyses (LA). Results Fifty-two regions distributed on 16 autosomes were detected. Most were identified with the LW or LD analyses, indicating both a large variability of effects in Large White in response to Heat stress, and high variability among the 10 Créole genomes segregating in the design. However, for thermoregulation traits, the majority of QTLs were detected with the LW model, suggesting interesting segregation of susceptibility and resistance alleles within the Large White breed. Ten regions were detected with the GxE model, mainly corresponding to significant effects in the temperate environment and no effect in the tropical situation, except for two regions on chromosome 2, which affected backfat thickness and growth rate, respectively. Twenty-four regions were detected for thermoregulation traits, but none were significant for both rectal and cutaneous temperatures. Of the 13 QTL regions detected for traits recorded during acute stress, four were also detected for similar traits during chronic stress, suggesting some consistency of responses during both stresses, although nine QTL regions were only detected during acute heat stress. Conclusions Measuring direct indicators of responses to heat stress, such as thermoregulatory responses, is essential to detect QTL and propose candidate genes involved in these responses. Multiple QTL for thermoregulatory responses segregate in the Large White breed were detected, paving the way for opportunities to select for heat stress resilience in European pig breeds
État des lieux clinique de la santé des pieds d’ovins dans un panel d’élevages allaitants touchés par une problématique de boiterie
No full textLameness is a major issue in the sheep industry, affecting animal welfare, performance and farm profitability. However, foot disorders, the main causes of lameness, are poorly documented in French meat sheep systems, limiting effective management of this problem. This study provides a clinical overview based on a review of current knowledge and a field study on seven farms in the Lot and Haute-Vienne. It highlights the diversity of lesions observed and their complex distribution depending on the farm, age and sex of the animals. The observation of lesions suggestive of contagious ovine digital dermatitis (CODD) raises the question of its emergence in France. These results underline the need for greater professional awareness, and the value of developing innovative tools, such as infrared thermography, to improve early detection and management of lameness.Les boiteries représentent un enjeu majeur de la filière ovine, impactant bien-être animal, performances et rentabilité des exploitations. Pourtant, les affections podales, principales causes de boiteries, sont mal documentées dans les systèmes ovins allaitants français, limitant la gestion efficace de cette problématique. Ce travail propose un état des lieux clinique fondé sur une revue des connaissances et une étude de terrain dans sept élevages du Lot et de la Haute-Vienne. Il met en évidence la diversité des lésions observées et leur distribution complexe selon les élevages, l’âge et le sexe des animaux. L’observation de lésions évocatrices de dermatite digitée contagieuse (CODD) soulève la question de son émergence en France. Ces résultats soulignent la nécessité d’une meilleure sensibilisation des professionnels, et l’intérêt de développer des outils innovants, comme la thermographie infrarouge, pour améliorer la détection précoce et la gestion des boiteries
P01-08 Impact of the food additives butylated hydroxyanisole and butylated hydroxytoluene on thyroid hormone hepatic catabolism in the HepaRG cell line
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Agir sur la génétique de l’hôte pour moduler la composition du microbiote : exemple chez le porc
No full textInternational audienceLes populations de microorganismes qui forment le microbiote sont caractérisée par leur diversité, les abondances relatives des genres bactériens ou leur assemblage en écosystèmes. Le rôle du microbiote, en particulier le microbiote intestinal, sur les performances de l’hôte est de mieux en mieux documenté chez les animaux d’élevage. Comprendre l’influence des caractéristiques de l’hôte et analyser les interactions hôte-microbiote est encore un vaste champ d’étude. En prenant comme exemple le porc, des résultats expérimentaux montrent les voies possibles de l’utilisation de leviers génétiques pour influencer la composition du microbiote. L’objectif, à terme, est d’élaborer des stratégies de sélection des populations animales en prenant en compte le microbiote pour mieux comprendre, prédire et piloter les phénotypes de l’hôte
Nucleoside Binding by a Surface Lipoprotein Governs Conjugative ICE Acquisition in Ruminant Mycoplasmas
No full textIntegrative and conjugative elements (ICEs) are major mediators of horizontal gene transfer (HGT) in bacteria. However, the role of recipient cells in their acquisition has received little attention. Using the ruminant pathogens Mycoplasma agalactiae and Mycoplasma bovis as minimal models, we combined genome-wide transposon mutagenesis with high-throughput mating assays to identify recipient factors required for ICE acquisition. The surface lipoprotein P48 emerged as the primary determinant of ICE uptake in both species. Structural and functional analyses revealed that P48 is the substrate-binding component of an ABC transporter with nucleoside-binding capacity. A single point mutation that abolished nucleoside binding drastically reduced ICE acquisition, demonstrating that P48-mediated nucleoside recognition is essential for conjugative transfer. However, ICE uptake did not require nucleoside transport, as inactivation of the transporter permease blocked nucleoside analog toxicity but not ICE invasion. Loss of P48 also triggered transcriptional activation of vestigial ICE genes, suggesting that surface recognition affects the intracellular state of the recipient. Remarkably, ICE transmission from recipient-derived donors was unaffected by P48 loss, underscoring its acquisition-specific role. Together, these results reveal a previously unrecognized, surface-exposed recipient factor critical for efficient ICE transfer in mycoplasmas and identify nucleotide binding as a central function in conjugation. By demonstrating that recipient-encoded functions can directly control ICE dissemination, this work challenges the donor-centric paradigm of bacterial conjugation and suggests new strategies to restrict horizontal gene flow in pathogenic and synthetic mycoplasmas
The mite Macrocheles robustulus (Mesostigmata, Macrochelidae) a new promising natural enemy of Haemonchus contortus (Strongylida, Trichostrongylidae)
No full textInternational audienceBackground Antiparasitic resistance in sheep necessitates non-chemical strategies for gastrointestinal strongylosis control. We have evaluated the potential of three predatory mite species-Macrocheles robustulus, Macrocheles muscaedomesticae and Rhabdocarpais consanguineus-to reduce transmission of the nematode Haemonchus contortus by preying on infective larvae.Methods Under laboratory conditions, mites were exposed to mixed prey environments containing housefly Musca domestica eggs and H. contortus third-stage (L3) larvae. Predation was first monitored over 8 h. This was followed by a more detailed assessment of M. robustulus predatory capacity in sheep feces containing eggs of H. contortus and then the oviposition capacity of females was studied when fed exclusively with L3 larvae. ResultsMacrocheles robustulus demonstrated a significant preference for nematode larvae, leading to further evaluation of its predatory capacity in sheep feces containing 2250 eggs per gram of H. contortus. After 14 days at 25 ± 2 °C, the presence of M. robustulus resulted in a significant reduction of L3 larvae compared to controls (519 vs. 1067 L3 larvae; p < 0.05). Additionally, M. robustulus females oviposited when fed exclusively on nematode larvae.Conclusions These findings suggest that M. robustulus could be a viable biological control agent against H. contortus in pasture settings, warranting further field studies.</div
GWASpipe: a Nexflow pipeline for GWAS analyses incorporating quality control
No full textInternational audienceGenome-wide association studies (GWAS) are powerful tools to link genetic variants with phenotypic traits. However, running GWAS involves several complex steps, including VCF preprocessing, quality control, population structure and relatedness correction, and selecting the right statistical models. We developed GWASpipe, an easy-to-use and automated pipeline to make GWAS more accessible, especially for non-expert users.GWASpipe is built with Nextflow[1] and follows nf-core standards. All tools are packaged in Singularity containers, ensuring reproducibility and easy deployment on any computing system. The pipeline includes :Data quality control, Filtering of low-quality variants and individuals, Population structure analysis, Kinship calculation, Association testing using two R packages (MM4LMM[2] et GAPIT[3]
Mélanges d’additifs alimentaires et risque de diabète de type 2: résultats de la cohorte NutriNet-Santé
No full textInternational audienceBackground: Mixtures of food additives are daily consumed worldwide by billions of people. So far, safety assessments have been performed substance by substance due to lack of data on the effect of multiexposure to combinations of additives. Our objective was to identify most common food additive mixtures, and investigate their associations with type 2 diabetes incidence in a large prospective cohort. Methods and Findings Participants ( n = 108,643, mean follow-up = 7.7 years (standard deviation (SD) = 4.6), age = 42.5 years (SD = 14.6), 79.2% women) were adults from the French NutriNet-Santé cohort (2009–2023). Dietary intakes were assessed using repeated 24h-dietary records, including industrial food brands. Exposure to food additives was evaluated through multiple food composition databases and laboratory assays. Mixtures were identified through nonnegative matrix factorization (NMF), and associations with type 2 diabetes incidence were assessed using Cox models adjusted for potential socio-demographic, anthropometric, lifestyle and dietary confounders. A total of 1,131 participants were diagnosed with type 2 diabetes. Two out of the five identified food additive mixtures were associated with higher type 2 diabetes incidence: the first mixture included modified starches, pectin, guar gum, carrageenan, polyphosphates, potassium sorbates, curcumin, and xanthan gum (hazard ratio (HR) per an increment of 1SD of the NMF mixture score = 1.08 [1.02, 1.15], p = 0.006), and the other mixture included citric acid, sodium citrates, phosphoric acid, sulphite ammonia caramel, acesulfame-K, aspartame, sucralose, arabic gum, malic acid, carnauba wax, paprika extract, anthocyanins, guar gum, and pectin (HR = 1.13 [1.08,1.18], p < 0.001). No association was detected for the three remaining mixtures: HR = 0.98 [0.91, 1.06], p = 0.67; HR = 1.02 [0.94, 1.10], p = 0.68; and HR = 0.99 [0.92, 1.07], p = 0.78. Several synergistic and antagonist interactions between food additives were detected in exploratory analyses. Residual confounding as well as exposure or outcome misclassifications cannot be entirely ruled out and causality cannot be established based on this single observational study. Conclusions This study revealed positive associations between exposure to two widely consumed food additive mixtures and higher type 2 diabetes incidence. Further experimental research is needed to depict underlying mechanisms, including potential synergistic/antagonist effects. These findings suggest that a combination of food additives may be of interest to consider in safety assessments, and they support public health recommendations to limit nonessential additives. Trial Registration The NutriNet-Santé cohort is registered at clinicaltrials.gov (NCT03335644). https://clinicaltrials.gov/study/NCT03335644 .Contexte : Les mélanges d’additifs alimentaires sont consommés quotidiennement par des milliards de personnes dans le monde. Jusqu’à présent, les évaluations de sécurité ont été menées substance par substance, faute de données sur les effets d’une multi-exposition à des combinaisons d’additifs. Notre objectif était d’identifier les mélanges d’additifs alimentaires les plus courants et d’examiner leurs associations avec l’incidence du diabète de type 2 dans une large cohorte prospective.Méthodes et résultats Les participants (n = 108 643, suivi moyen = 7,7 ans [écart-type (ET) = 4,6], âge = 42,5 ans [ET = 14,6], 79,2 % de femmes) étaient des adultes de la cohorte NutriNet-Santé (France, 2009-2023). Les apports alimentaires ont été évalués à l’aide de rappels alimentaires de 24 heures répétés, incluant l’identification des marques industrielles consommées. L’exposition aux additifs a été estimée grâce à plusieurs bases de données de composition alimentaire et des dosages en laboratoire. Les mélanges ont été identifiés au moyen de la factorisation en matrices non négatives (NMF), et les associations avec l’incidence du diabète de type 2 ont été étudiées par modèles de Cox ajustés sur les facteurs sociodémographiques, anthropométriques, de mode de vie et alimentaires. Au total, 1 131 participants ont développé un diabète de type 2. Deux des cinq mélanges identifiés étaient associés à une incidence plus élevée de diabète de type 2 : le premier incluait amidons modifiés, pectine, gomme de guar, carraghénanes, polyphosphates, sorbate de potassium, curcumine et gomme xanthane (rapport de risque [RR] pour un incrément d’1 ET du score NMF = 1,08 [1,02–1,15], p = 0,006) ; le second regroupait acide citrique, citrates de sodium, acide phosphorique, caramel ammoniacal au sulfite, acésulfame-K, aspartame, sucralose, gomme arabique, acide malique, cire de carnauba, extrait de paprika, anthocyanes, gomme de guar, et pectine (RR = 1,13 [1,08–1,18], p < 0,001). Aucune association n’a été détectée pour les trois autres mélanges (RR = 0,98 [0,91–1,06], p = 0,67 ; RR = 1,02 [0,94–1,10], p = 0,68 ; et RR = 0,99 [0,92–1,07], p = 0,78). Plusieurs interactions synergiques et antagonistes entre additifs ont été observées en analyses exploratoires. Un résidu de confusion ainsi que des erreurs possibles d’exposition ou de classification de l’issue ne peuvent être totalement exclus, et la causalité ne peut être établie sur la seule base de cette étude observationnelle.Conclusions Cette étude met en évidence une association positive entre l’exposition à deux mélanges d’additifs alimentaires largement consommés et l’incidence du diabète de type 2. De nouvelles recherches expérimentales sont nécessaires pour mieux comprendre les mécanismes sous-jacents, y compris les effets synergiques ou antagonistes potentiels. Ces résultats suggèrent que la prise en compte des combinaisons d’additifs pourrait être pertinente dans les évaluations de sécurité, et soutiennent les recommandations de santé publique visant à limiter les additifs non essentiels.Enregistrement de l’étude La cohorte NutriNet-Santé est enregistrée sur clinicaltrials.gov (NCT03335644)