HAL ENVT (Ecole Nationale Vétérinaire de Toulouse)
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Whole genome short read data from 567 bulls of 14 breeds provides insight into genetic diversity of French cattle
International audiencePolymorphism approximately 15x depth on the Illumina Novaseq60 0 0 platform. We detected 34,252,080 variants, 25,115,987 of which were already known in the Ensembl variation database version 110 and 9,136,093 were absent and were considered as novel variants. This data set represents a useful resource for the community to better identify SNPs or indels such as mutation anticipation and provides new insights into bovine genetic diversity.In this work, we sequenced 567 bulls from 14 different breeds (Holstein, Montbéliarde, Normande, Brown Swiss, Simmental, Abondance, Tarentaise, Vosgienne, Blonde d'Aquitaine, Charolaise, Limousine, Aubrac, Flamande, Parthenaise). Each sample was sequenced at an approximately 15x depth on the Illumina Novaseq6000 platform. We detected 34,252,080 variants, 25,115,987 of which were already known in the Ensembl variation database version 110 and 9,136,093 were absent and were considered as novel variants. This data set represents a useful resource for the community to better identify SNPs or indels such as mutation anticipation and provides new insights into bovine genetic diversity
Maternal emulsifier consumption alters the offspring early-life microbiota and goblet cell function leading to long-lasting diseases susceptibility
International audienceEarly-life acquisition of microbiota and, consequently, immune system development, both lastingly impacts health. Accordingly, we hypothesized that disturbing the microbiota of lactating mothers via consumption of dietary emulsifiers might alter the microbiota, and perhaps the immune system, of their offspring, thereby increasing susceptibility to microbiota-mediated diseases, including colitis and metabolic syndrome. Here we report that, in mice, maternal consumption of carboxymethylcellulose and polysorbate-80 resulted in transient alterations in offspring microbiotas that were necessary and sufficient to increase proneness to colitis and metabolic syndrome in young adulthood. Offspring microbiome alterations induced by maternal emulsifier consumption resulted in elevated levels of pro-inflammatory flagellin, bacterial encroachment, and premature closure of goblet cell associated antigens passages (GAPs). The latter event was linked to phenotypic outcome in that pharmacologically preventing GAP closure eliminated the detrimental of maternal emulsifier consumption. Collectively, these results illustrate the potential of dietary emulsifiers to drive transgenerational microbiota alteration and, consequently, hastened immune development that increases susceptibility to inflammatory diseases
Eaux usées de l’ENVT : état des lieux et focus sur les concentrations d’antibiotiques et de bactéries résistantes aux antibiotiques
This study aims to evaluate a state of play on the matter of antibiotic resistance in Toulouse National Veterinary School waste waters, by tackling legislative, logistical and scientific aspects through the combination of a bibliographic and experimental study included in a “One health” approach. The consumption of antibiotics on site was also assessed and quantified based on drugs orders data. The experiments conducted on the campus’ wastewater included the research and identification of bacterial resistances to various antibiotics, the research and quantification of antibiotic residues and the characterization of the bacterial population they shelter. Many antibiotic residues have been detected, as well as bacteria with varied resistance profiles, as can be observed in wastewater.Cette étude a pour objectif de dresser un état des lieux sur la question de l’antibiorésistance dans les eaux usées de l’École Nationale Vétérinaire de Toulouse, en abordant des aspects règlementaires, logistiques et scientifiques par combinaison d’une étude bibliographique et expérimentale inclue dans une approche « One health ». La consommation d’antibiotique sur site a également été étudiée et quantifiée sur la base de données de commandes de médicaments. Les expériences menées sur les eaux usées émises par le campus incluaient la recherche et l’identification de résistances bactériennes à différents antibiotiques, la recherche et la quantification de résidus d’antibiotiques ainsi que la caractérisation des populations bactériennes qu’elle contient. De nombreux résidus d’antibiotiques ont été détectés, ainsi que des bactéries aux profils de résistance variés, comme cela peut être observé dans des eaux usées
Health and environmental benefits of the design of a novel hybrid food mixing meat and mushroom
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Étude morphologique de l’humérus du chien : application à l’abord de la coulisse bicipitale
This experimental work, focused on the study of the proximal humerus morphology in dogs, enabled the development of a transosseous approach to the bicipital groove. The analysis of anatomical landmarks on humeri with varying morphologies allowed us to identify reliable reference points, thereby facilitating practical application. This preliminary study serves as a foundation for the future development of an arthroscopic tenodesis technique aimed at treating bicipital tendinopathies which is a common condition causing lameness in dogsCe travail expérimental, consacré à l’étude de la morphologie de l’humérus proximal chez le chien, a été construit dans le but de développer une approche trans-osseuse de la coulisse bicipitale. L’analyse des repères anatomiques sur des humérus présentant des morphologies variées nous a permis d’identifier des points de référence fiables, facilitant ainsi une application pratique. Cette étude préliminaire constitue une base pour le développement futur d’une technique arthroscopique de ténodèse, destinée au traitement des tendinopathies bicipitales — une affection fréquente à l’origine de boiteries chez le chien
Therapeutic Drug Monitoring of Long-Acting Cabotegravir and Rilpivirine in a National Cohort of People With Human Immunodeficiency Virus Type 1: First Results From the ANRS-MIE CARLAPOP Study
International audienceBackground: The impact of pharmacokinetic variability of cabotegravir (CAB) and rilpivirine (RPV) long-acting (LA) injectable therapy on virological outcomes remains controversial. This study aimed to characterize the variability of CAB and RPV trough concentrations (Ctrough) and to identify the predictors of suboptimal exposure and virologic failure (VF) in a large real-world cohort.Methods: We conducted a multicenter observational study including people with human immunodeficiency virus type 1 (HIV-1) initiating LA-CAB/RPV as maintenance therapy from January to December 2022, in whom CAB and RPV plasma Ctrough were determined as part of therapeutic drug monitoring (TDM).Results: A total of 1674 CAB and 1687 RPV Ctrough measurements were collected from 736 people with HIV-1 (PWH). Significant interindividual variability in concentrations was observed. At month 1/month 3, 20%-30% of PWH had Ctrough <1120 ng/mL for CAB and 32 ng/mL for RPV. Predictors of lower Ctrough were body mass index (BMI) ≥30 kg/m2 and female sex at month 1, and only male sex at steady state. After a median follow-up of 12 (interquartile range, 9-16) months, VF occurred in 2.5% of PWH. At month 6 and month 12, VF was significantly associated with the presence of at least 2 risk factors (obesity, suboptimal Ctrough) (odds ratio [OR], 4.6, P = .047; OR, 5.15, P = .014), and CD4 nadir (OR, 0.56, P = .008; OR, 0.5, P = .001).Conclusions: Our large real-world study confirms significant variability in CAB and RPV exposure, with BMI and sex as key predictors of lower Ctrough. Suboptimal CAB and RPV Ctrough, particularly in people with obesity, increases the risk of VF during the first year of treatment, highlighting the usefulness of TDM in clinical practice
Ablation of Hepatocyte Derived‐ FGL1 Does Not Aggravate Metabolic Dysfunction‐Associated Steatotic Liver Disease
International audienceMetabolic dysfunction‐associated steatotic liver disease (MASLD) begins with simple steatosis, which can progress to hepatocellular carcinoma (HCC). The pathogenesis of MASLD alters the secretion of hepatokines such as fibrinogen‐like 1 (FGL1), a candidate mediator of liver steatosis and hyperglycemia. To investigate the contribution of FGL1 to liver diseases, we compared wild‐type mice to mice with hepatocyte‐specific deletion of Fgl1 subjected to a steatosis or HCC experimental protocol. We found that mice deficient for Fgl1 in hepatocytes showed higher levels of plasma glucose, pronounced metabolic alterations, and liver injury when fed a western diet compared to their wild‐type counterparts. However, both genotypes exhibited similar lipid deposition in the liver. Similarly, wild type and Fgl1 ‐deficient mice displayed comparable liver alterations during HCC progression. We observed that FGL1 expression was repressed during MASLD progression in mice and humans concomitantly with the severity of liver injury. Altogether, these findings suggest that FGL1 is not a major contributor to the pathogenesis of MASLD and HCC
Multi-block analyses reveal that standing activity on the day of farrowing and newborn aggression are main factors contributing to litter survival and growth in primiparous sows among a hundred maternal traits
International audienceWe used a crossbreeding design between the Meishan and Large White breeds to cover a maximum of the variability existing in maternal populations. We considered the sow as a system and our objectives were 1/ to explore the relationships between groups of functional or behavioural traits and 2/ to quantify their importance for litter mortality and growth during the 1st week of lactation. The primiparous sows were reared in individual pens with straw on the floor. Their activity was measured automatically by computer vision and we usedCLR data from daily time budget on postures and standing activity (eating, drinking, exploring). Their responsiveness to humans and piglets was assessed by on-farm notations. We measured 100 maternal traits and grouped them into 11 blocks : X1 Farrowing performance and environment; X2 Body reserves at maternity entry; X3 Udder quality; X4 Reactivity at maternity entry; X5 Reactivity at farrowing; X6 Standing activity before D0; X7 Postural activity at D0; X8 Postural activity after D0; X9 Standing activity before D0; X10 Standing activity at D0; X11 Standing activity after D0. Functional and behavioural predictors of the proportion of dead piglets to live-born piglets and litter weight gain, which were calculated for three periods after birth (D0-D1, D1-D3 and D3-D7), were adjusted for the effects of breed and litter size. Multi-block partial least squares analyses were applied separately to mortality and growth traits. The hundred traits explained 85% of the variation in the mortality block and 79.6% of that in the growth block. X3 and X7 had a significant effect (P<0.05) and together explained ~25% of mortality and ~30% of growth. X10 explained 15.8% of mortality (P<0.05) and X2, X5, X9 had a contribution ≥ 9.8% each. Time spent eating and exploring while standing in the first 24 hours after the onset of farrowing influenced mortality and growth significantly. Time spent lying on the side at D0 and newborn aggression also influenced litter mortality. Teat functionality and diameter influenced growth. Sow behaviour plays an important role in early piglet production
Genomics for non-specific disease resistance in rabbits
MasterThe widespread use of antibiotics in animal farming contributes to the development of antimicrobial resistance, posing a major public health challenge. In rabbits, breeding for non-specific disease resistance emerges as a promising strategy to reduce antibiotic use. This study investigates the genetic of non-specific disease resistance in rabbits though phenotypic analysis, genome wide association studies, and family-based Transmission Disequilibrium Tests. Two rabbits line one selected for resistance over six generations and one non-selected. Genome wide association studies identified several significant genomic regions associated with resistance traits, particularly on chromosome 12, 13, 16 and 17. A targeted analysis of a high morbidity rabbit family also revealed suggestive loci on chromosome 7, 8 and 16. These findings highlight the genetic variability underlying disease resistance, suggest a possible polygenic determinism for the disease resistance and support the potential of selective breeding as a sustainable alternative to antibiotics in rabbits’ production
Genome-wide characterization of parent-of-origin expression in piglets targets novel imprinted genes involved in neurodevelopmental and fetal growth functions
International audienceGenomic imprinting is still poorly characterized in pigs. Indeed, most studies focused on humans and mice. Although imprinted loci have been identified in livestock, their investigation remains limited. Moreover, as identification of imprinted livestock genes has primarily targeted well-known orthologous genes in humans and mice, it has also restricted the discovery of imprinted genes specific to these species (1,2). However, studies in livestock have highlighted the contribution of imprinted genes in agro-economic traits (3), emphasizing the need to improve our knowledge about genomic imprinting mechanisms in these species.Here, we investigated genomic imprinting in piglets around birth using an extensive and unbiased genome-wide approach across hypothalamus, loin and placenta, based on omics data from reciprocal crosses between two pig breeds : Large White (LW) and Meishan (MS). Why identify genomic imprinting in pigs ?Samples & Data An unbiased and extensive approach Imprinted genes identified across tissues, novelties linked to fetal and neurodevelopmental growthThis project aims to identify parent-of-origin expressed genes with a strong to exclusive parental expression, called imprinted genes, in a genome-wide manner without a priori :We identified 112 unique genes including 61, 37, and 38 genes in the hypothalamus, loin and placenta, respectively, showing a high to exclusive parental bias ranging from between 25/75 and 0/100. Some well-known imprinted genes located in clusters, such as IGF2, DLK1 and MEST were identified, confirming our strategy.The conservation of imprinted genes and their parent-of-origin patterns were not as conserved between species as previously thought with only about thirty genes shared between pigs, humans and mice. We also observed few conservation between tissues.We identified novel parent-of-origin expressed genes shared between the hypothalamus and loin, which appear to be involved in neurodevelopmental and fetal growth mechanisms. A.A. Ideogram representing the overlap between all genes identified accross the hypothalamus, loin and placenta showing a high to exclusive parental bias (from 75/25 to 0/100) and their human and murine orthologs. Only well-known imprinted clusters/genes were conserved across species. B. Venn diagram summarizing common genes found between the hypothalamus, loin and placenta.Well-known imprinted genes were identified such as CDKN1C, IGF2 and MEST. New candidate genes were also identified including FAM20B, HSD17B11,PITRM1 and POU6F2. C. Boxplot showing the read distribution between parental alleles in the hypothalamus and loin, for FAM20B, HSD17B11,PITRM1 and POU6F2 genes. D. Table summarizing the functions FAM20B, HSD17B11,PITRM1 and POU6F2 genes reported in mouse, involving growth and neurodevelopmental mechanisms (highlighted in grey), A. B. C.A. Pipeline. After pre-processing and variant calling, we selected only informative variants for each piglet. Then, we intersected genomic and transcriptomic data from hypothalamus, loin and placenta, resulting in a pool of informative variants expressed in each tissue. We sorted reads mapping to each variant according to their allele and parent-of-origin distribution. Following this step, we performed Fisher's exact tests, allowing us to distinguish the parent-of-origin expression (POE) and Allele Specific Expression (ASE) and to statistically determine which of POE or ASE is more significant. B. Variant distribution. We plotted each variant according to its POE and ASE p-values (-log10). We identified 450, 267 and 459 variants that were significant for POE (Bonferonni correction; alpha < 0,01) in hypothalamus, loin and placenta respectively. These variants targeted 174, 78 and 239 genes in each tissue, representing a total of 440 unique genes. C. Heatmap. We plotted the parental expression bias of each gene. Weak/moderate (ratios from 50/50 to 75/25) to high/exclusive ratios (> 75/25) were observed. Respectively, 61, 37 and 38 genes in the hypothalamus, loin and placenta showed a high to exclusive parental bias.</div