HAL ENVT (Ecole Nationale Vétérinaire de Toulouse)
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HUMESS: integrating quantitative transcriptomic analysis and metabolic modeling to unveil condition-specific gene signatures
No full textInternational audienceSummary Transcriptomic analysis is a key tool for exploring gene expression, but the complexity of biological systems often limits its insights. In particular, the lack of intermodal or multi-layered analysis hinders the ability to fully capture key cellular functions such as metabolism from transcriptomic data alone. Here, we introduce a novel approach that informs transcriptomic data analysis with metabolic network modeling to address this. Unlike traditional methods, HUman MEtabolism Specific Signature (HUMESS) uses genome-scale metabolic modeling and flux analysis to highlight reactions and involved genes based on their metabolic significance, offering a deeper understanding of transcriptomic data. Our computational pipeline, supported by a user-friendly Rshiny application, enhances gene expression analysis by uncovering metabolic phenotypic signatures.Availability and implementationHUMESS is open source and available under GitLab https://gitlab.univ-nantes.fr/bird_pipeline_registry/humess with the complete documentation available at https://gitlab.univ-nantes.fr/bird_pipeline_registry/humess/-/wikis/Home. A zenodo archive is also available at the following DOI: https://doi.org/10.5281/zenodo.15487717. An RShiny application has been developed to facilitate the exploration and analysis of HUMESS’s results. The app is available online at the following address: https://shiny-bird.univ-nantes.fr/app/shinymess but can also be installed locally, available under GitLab https://gitlab.univ-nantes.fr/pare-l/shinymess
Barriers and levers of biosecurity on small-scale poultry farms selling directly to consumers
No full textInternational audienceFor the past decade, Highly Pathogenic Avian Influenza (HPAI) outbreaks have severely impacted the global poultry industry, leading to biosecurity regulations. Small-scale poultry farms selling directly to consumers have faced challenges in implementing these measures due to their specific characteristics. Using the analytical framework of “sociotechnical system”, this study has analysed qualitative data from 36 semi-structured interviews conducted in two French poultry production areas between January and October 2023. Small-scale poultry production has been characterised by heterogeneity, strong professional identity, and stability. However, recurrent HPAI epidemics and regulations have disrupted this balance, creating tensions between biosecurity guidelines and farming practices (e.g. access restrictions), values (free-range farming), workload, financial sustainability, and relations with government authorities. Various adaptations emerged in the field, although they were limited to a small proportion of producers. This suggest that biosecurity compliance on small-scale farms cannot be achieved without simultaneously addressing the social, technical, and regulatory issues
Towards collective biosecurity: a participatory approach in French communities of poultry farmers
No full textInternational audienceBiosecurity approaches have traditionally been implemented at the individual farm level. However, in light of major outbreaks of highly pathogenic avian influenza in the French poultry sector in recent years, individually-framed approach to biosecurity have become increasingly insufficient to control disease risks for farms that are epidemiologically interconnected through geographic proximity, shared equipment, personnel or animals. An alternative approach is to consider biosecurity more collectively at the level of a functional or geographic territory defined by shared risks. This study implemented a participatory approach to help farmers conceptualize biosecurity collectively, and to assess the approach’s impact on relationship dynamics within farmers’ communities. Individual interviews and four participatory workshops were designed to (1) identify shared motivations, values, and needs within communities, (2) identify shared risk factors, (3) foster understanding of epidemiological risks through expert discussions, and (4) identify collective, context-adapted solutions. Two farming communities in France were identified, consisting of seven and nine stakeholders, mainly chicken and duck farmers, from diverse production systems. Data were collected throughout the research process using full recording and transcription of the workshops. The results suggested that farmers’ shared values prioritized autonomy and quality of production, and that farmers perceived risks such as wildlife and wind transmission as major concerns over which they felt powerless to act. This study also highlighted the difficulty of engaging all stakeholders in collective biosecurity management. However, the participatory process generated enthusiasm. Many farmers, disillusioned by top-down biosecurity policies, welcomed a more inclusive, context-sensitive approach. The findings emphasized the role of key farmers as “pivot stakeholders” who can engage their peers and facilitate the shift towards a territorial-scale biosecurity strategy. The follow-up of farmers’ communities over a longer time frame should provide new insights on the collective actions which can be implemented by farmers as a group to manage infectious diseases
Optimization of phosphorus dendrimer analysis by MALDI-TOF
No full textInternational audienceDendrimers are tree-like macromolecules studied in various fields of application (materials, catalysis, biology...). Because of their good compatibility with living systems, phosphorus-containing dendrimers can be used in biology, particularly as drug carriers. The use of dendrimers as drug carriers can enhance their activity and facilitate targeting and cellular penetration. Various antiinfectious agents were grafted onto the periphery of cyclotriphosphazene-cored phosphorus-containing dendrimers. MALDI ionization is the method of choice for analyzing these high-mass molecules, but the results obtained are highly dependent on the preparation of the deposit, the nature of the matrix used and whether alkali metal salts are added or not to the preparation.</div
Net Reproduction Number as a Real-Time Metric of Population Reproducibility
No full textInternational audienceThe total fertility rate (TFR) is a biased estimate of the population reproductive potential when there is a sex-ratio imbalance at birth, and it does not account for the mortality of women of childbearing age. This study aimed to estimate the reproduction rate (R t ), which adjusts for the sex-ratio imbalance and the mortality of women of childbearing age, and to assess the differences in the timing of when the population reached the replacement level of the TFR and R t . We first estimated the R t using the probability of survival in women and the number of female births. Then, using a time-series analysis, we compared the time series of the TFR and R t in the Korean population between 1975 and 2022. We found the R t showed a below replacement level of the population a year earlier than the TFR. However, the estimate of the time-series analysis of R t was not significantly different from the estimates of the TFR. Our finding suggests that the R t can provide timely information on the adjusted population reproductive potential and is easier for the public to interpret compared to TFR
Screening of mediterranean agro-industrial by-products rich in phenolic compounds for their ability to modulate in vitro ruminal fermentation
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Identification of Functional Cellular Markers Related to Human Health, Frailty and Chronological Age
No full textInternational audienceABSTRACT Aging leads to a decline in physiological reserves, an increase in age‐related diseases, reduced functional ability and a shortened healthspan. While molecular markers of chronological aging exist, their link to general health and intrinsic capacity (IC), a composite measure of physical and mental capacities, remains unclear. This study integrates the WHO's Healthy Aging framework with geroscience to explore fibroblasts as indicators of health. We assessed primary skin fibroblasts from 133 individuals aged 20–96, evaluating their ability to maintain tissue structure, modulate immune responses and regulate metabolism (SIM functions). By combining functional and molecular analyses, we investigated the relationship between fibroblast performance, chronological age and IC. Our results demonstrate that fibroblast SIM functions are modified with stressors and age, correlating with IC rather than just chronological age. Notably, fibroblasts from pre‐frail and frail individuals exhibited reduced mitochondrial respiration and lower extracellular periostin levels, with periostin being able to capture IC status, irrespective of age and sex, reflecting a cellular ‘health memory’. The SIM paradigm provides a complementary framework to the established hallmarks of aging, advancing our understanding of how cellular aging impacts functional decline. These findings suggest that fibroblast‐derived markers could serve as indicators of frailty and reduced IC, enabling early detection of individuals at risk for health deterioration and laying the foundation for early identification of functional decline
L’élevage de ruminants s’adaptera-t-il au changement climatique ? Impacts et leviers d’adaptation
No full textInternational audienceConsequences of climate change for ruminant farming are numerous, from forage to animals. Heat stress has consequences on animal production,reproduction, well-being and health. For grasslands and fodder, climate change means changes in production periods and greater inter-annualvariability. There are various, complementary ways of adapting to this problem: adapting the animal by improving its heat tolerance and, moregenerally, its efficiency, robustness and resilience; improving its living conditions on pasture and in buildings; and ensuring the balance of the foragesystem by influencing supply through the diversification and complementarity of forage resources, and demand (the animals’ needs) by adjustingstocking levels and herd management to ensure that the needs coincide with the seasonal nature of the grasslands. Methods and tools exist tohelp farmers determine which levers are best suited to their system, and to support them in building an adaptation strategy that combines them aseffectively as possible. These adaptation approaches require anticipation and the involvement of all those involved in research and development.Les conséquences du changement climatique sur l’élevage de ruminants sont nombreuses. Elles affectent autant les animaux que les fourrages. Le stress thermique a des conséquences sur la production, la reproduction, le bien-être et la santé des animaux. Pour les prairies et fourrages, les évolutions climatiques se traduisent notamment par des modifications des périodes de production et une accentuation de la variabilité interannuelle. Les voies d’adaptation pour répondre à cette problématique sont diverses et complémentaires : adapter l’animal en améliorant sa tolérance à la chaleur et de façon générale son efficience, sa robustesse et sa résilience ; améliorer ses conditions de vie au pâturage et en bâtiment ; et assurer l’équilibre du système fourrager en jouant sur l’offre via la diversification et la complémentarité des ressources fourragères, et la demande (les besoins des animaux) en ajustant le chargement et la conduite des troupeaux pour faire coïncider les besoins avec la saisonnalité des prairies. Des méthodes et outils existent pour aider les éleveurs à déterminer les leviers les plus adaptés à leur système, et pour les accompagner dans la construction d’une stratégie d’adaptation les combinant au mieux. Ces démarches d’adaptation nécessitent de l’anticipation et l’implication des filières dans leur ensemble
Hartmann’s procedure versus primary anastomosis for Hinchey III or IV sigmoid diverticulitis: a propensity score analysis of a retrospective national cohort study
No full textInternational audienceIntroduction: Primary anastomosis with a diverting stoma (PA) has been evaluated relative to Hartmann's procedure (HP) for Hinchey III/IV peritonitis in four randomized trials, all of which lacked power. We aimed to evaluate the safety of PA for this indication in real-life settings.Patients and methods: Patients who underwent surgery for Hinchey III/IV diverticulitis at 43 French centers from 2010 to 2021 were included in this retrospective multicenter study. The primary endpoint was the rate of severe complications at 90 days (Clavien-Dindo III-V). Secondary endpoints included the overall complication rate and stoma-free survival at one year. Two groups of patients (PA vs. HP) were created by propensity score matching (PSM).Results: In total, 651 patients were included (112 with PA and 539 with HP). We matched 102 of the patients with PA with 102 patients who underwent HP. On day 90, there was no difference in the rate of severe complications (31% vs. 29%, p = 0.75) between these groups in subgroup analyses for Hinchey III (p = 0.99) or Hinchey IV (p = 0.35) diverticulitis. The percentages of patients with Hinchey III or IV diverticulitis did not differ significantly between the groups (SMD = 0.03). After inverse probability treatment weighting, mortality was significantly higher in the HP group than in the PA group (6% vs. 1%, p = 0.019). Stoma-free survival at one year was higher in the PA group (85% vs. 73%, p = 0.03). The reoperation rate at 90 days was higher in the PA group than in the HP group (unadjusted: 21% vs. 13%, p = 0.028; PSM: 21% vs. 7%, p = 0.007, respectively).Conclusion: PA did not increase the overall rate of complications. Conversely, it decreased mortality and the rate of definitive stomas in a large cohort of patients with Hinchey III/IV sigmoid diverticulitis
IsoDesign: software for optimizing the isotopic composition of labeled substrates in 13C-fluxomics experiments
No full textInternational audienceThe study of metabolic fluxes provides a detailed phenotypic and functional description of cellular metabolism, contributing to a better understanding of biological processes. Metabolic Flux Analysis (MFA) encompasses a set of approaches used to quantify biochemical reaction rates within metabolic networks, relying on mathematical modeling methods.13C-MFA is an approach that leverages isotopic data from stable carbon-13 (13C) labeling experiments to calculate metabolic fluxes. The ability to compute fluxes of interest and their accuracy strongly depend on the experimental design, particularly on the choice of labeled substrates.However, determining and selecting the optimal labeling configurations of substrates is a complex and time-consuming task, requiring the exploration of multiple labeling configurations within a vast solution space. This selection is even more challenging as it depends on optimizing flux accuracy, analytical capabilities, and the often high cost of labeled substrates, making the analysis of possible combinations even more complex.To accelerate this process, we have developed IsoDesign, an open-source Python tool (https://github.com/MetaboHUMetaToul-FluxoMet/IsoDesign) dedicated to optimizing the isotopic composition of labeled substrates for 13C-fluxomics experiments. With its intuitive graphical interface and the use of the influx si software (https://github.com/sgsokol/influx) for flux calculation, IsoDesign facilitates the design of isotopic labeling experiments, improving accuracy and reducing the cost of 13C-MFA experiments