Review. Divergent selection for residual feed intake in the growing pig

To view supplementary material for this article, please visit https:/doi.org/10.1017/S175173111600286XThis review summarizes the results from the INRA (Institut National de la Recherche Agronomique) divergent selection experiment on residual feed intake (RFI) in growing Large White pigs during nine generations of selection. It discusses the remaining challenges and perspectives for the improvement of feed efficiency in growing pigs. The impacts on growing pigs raised under standard conditions and in alternative situations such as heat stress, inflammatory challenges or lactation have been studied. After nine generations of selection, the divergent selection for RFI led to highly significant ( P<0.001) line differences for RFI (−165 g/day in the low RFI (LRFI) line compared with high RFI line) and daily feed intake (−270 g/day). Low responses wereobserved on growth rate (−12.8 g/day, P <0.05) and body composition (+0.9mm backfat thickness, P = 0.57; −2.64% lean meat content, P<0.001) with a marked response on feed conversion ratio (−0.32 kg feed/kg gain, P<0.001). Reduced ultimate pH and increased lightness of the meat ( P<0.001) were observed in LRFI pigs with minor impact on the sensory quality of the meat. These changes in meat quality were associated with changes of the muscular energy metabolism. Reduced maintenance energy requirements (−10% after five generations of selection) and activity (−21% of time standing after six generations of selection) of LRFI pigs greatly contributed to the gain in energy efficiency. However, the impact of selection for RFI on the protein metabolism of the pig remains unclear. Digestibility of energy and nutrients was not affected by selection, neither for pigs fed conventional diets nor for pigs fed high-fibre diets. A significant improvement of digestive efficiency could likely be achieved by selecting pigs on fibre diets. No convincing genetic or blood biomarker has been identified for explaining the differences in RFI, suggesting that pigs have various ways to achieve an efficient use of feed. No deleterious impact of the selection on the sow reproduction performance was observed. The resource allocation theory states that low RFI may reduce the ability to cope with stressors,via the reduction of a buffer compartment dedicated to responses to stress. None of the experiments focussed on the response of pigs to stress or challenges could confirm this theory. Understanding the relationships between RFI and responses to stress and energy demanding processes, as such immunity and lactation, remains a major challenge for a better understanding of the underlying biological mechanisms of the trait and to reconcile the experimental results with the resource allocation theory

Passive Sampling as a Tool to Assess Atmospheric Pesticide Contamination Related to Vineyard Land Use

The massive use of pesticides in agriculture has led to widespread contamination of the environment, particularly the atmospheric compartment. Thirty-six pesticides, most used in viticul-ture, were monitored in ambient air using polyurethane foams as passive air samplers (PUF-PAS). Spatiotemporal data were collected from the samplers for 10 months (February–December 2013), using two different sampling times (1 and 2 months) at two different sites in a chateau vineyard in Gironde (France). A high-volume active air sampler was also deployed in June. Samples were extracted with dichloromethane using accelerated solvent extraction (ASE) (PUFs from both passive and active) or microwave-assisted extraction (MAE) (filters from active sampling). Extracts were analyzed by both gas and liquid chromatography coupled with tandem mass spectrometry. A total of 23 airborne pesticides were detected at least once. Concentrations in PUF exposed one month ranged from below the limits of quantification (LOQs) to 23,481 ng PUF−1. The highest concentrations were for folpet, boscalid, chlorpyrifos-methyl, and metalaxyl-m—23,481, 17,615, 3931, and 3324 ng PUF−1. Clear seasonal trends were observed for most of the pesticides detected, the highest levels (in the ng m−3 range or the µg PUF−1 range) being measured during their application period. Impregnation levels at both sites were heterogeneous, but the same pesticides were involved. Sampling rates (Rs) were also estimated using a high-volume active air sampler and varied significantly from one pesticide to another. These results provide preliminary information on the seasonality of pesticide concentrations in vineyard areas and evidence for the effectiveness of PUF-PAS to monitor pesticides in ambient air. © 2022 by the authors. Licensee MDPI, Basel, Switzerland.COntinental To coastal Ecosystems: evolution, adaptability and governanc

Transcriptional Profiling of Human Brain Endothelial Cells Reveals Key Properties Crucial for Predictive In Vitro Blood-Brain Barrier Models

Brain microvascular endothelial cells (BEC) constitute the blood-brain barrier (BBB) which forms a dynamic interface between the blood and the central nervous system (CNS). This highly specialized interface restricts paracellular diffusion of fluids and solutes including chemicals, toxins and drugs from entering the brain. In this study we compared the transcriptome profiles of the human immortalized brain endothelial cell line hCMEC/D3 and human primary BEC. We identified transcriptional differences in immune response genes which are directly related to the immortalization procedure of the hCMEC/D3 cells. Interestingly, astrocytic co-culturing reduced cell adhesion and migration molecules in both BECs, which possibly could be related to regulation of immune surveillance of the CNS controlled by astrocytic cells within the neurovascular unit. By matching the transcriptome data from these two cell lines with published transcriptional data from freshly isolated mouse BECs, we discovered striking differences that could explain some of the limitations of using cultured BECs to study BBB properties. Key protein classes such as tight junction proteins, transporters and cell surface receptors show differing expression profiles. For example, the claudin-5, occludin and JAM2 expression is dramatically reduced in the two human BEC lines, which likely explains their low transcellular electric resistance and paracellular leakiness. In addition, the human BEC lines express low levels of unique brain endothelial transporters such as Glut1 and Pgp. Cell surface receptors such as LRP1, RAGE and the insulin receptor that are involved in receptor-mediated transport are also expressed at very low levels. Taken together, these data illustrate that BECs lose their unique protein expression pattern outside of their native environment and display a more generic endothelial cell phenotype. A collection of key genes that seems to be highly regulated by the local surroundings of BEC within the neurovascular unit are presented and discussed

Homologous recombination deficiency and cyclin E1 amplification are correlated with immune cell infiltration and survival in high-grade serous ovarian cancer

Background: How molecular profiles are associated with tumor microenvironment (TME) in high-grade serous ovarian cancer (HGSOC) is incompletely understood. Therefore, we analyzed the TME and molecular profiles of HGSOC and assessed their associations with overall survival (OS). Methods: Patients with advanced-stage HGSOC treated in three Dutch hospitals between 2008–2015 were included. Patient data were collected from medical records. BRCA1/2 mutation, BRCA1 promotor methylation analyses, and copy number variations were used to define molecular profiles. Immune cells were assessed with immunohistochemical staining. Results: 348 patients were categorized as BRCA mutation (BRCAm) (BRCAm or promotor methylation) (30%), non-BRCA mutated HRD (19%), Cyclin E1 (CCNE1)-amplification (13%), non-BRCAmut HRD and CCNE1-amplification (double classifier) (20%), and no specific molecular profile (NSMP) (18%). BRCAm showed highest immune cell densities and CCNE1-amplification lowest. BRCAm showed the most favorable OS (52.5 months), compared to non-BRCAmut HRD (41.0 months), CCNE1-amplification (28.0 months), double classifier (27.8 months), and NSMP (35.4 months). Higher immune cell densities showed a favorable OS compared to lower, also within the profiles. CD8+, CD20+, and CD103+ cells remained associated with OS in multivariable analysis. Conclusions: Molecular profiles and TME are associated with OS. TME differs per profile, with higher immune cell densities showing a favorable OS, even within the profiles. HGSOC does not reflect one entity but comprises different entities based on molecular profiles and TME

A Solve-RD ClinVar-based reanalysis of 1522 index cases from ERN-ITHACA reveals common pitfalls and misinterpretations in exome sequencing

Purpose Within the Solve-RD project (https://solve-rd.eu/), the European Reference Network for Intellectual disability, TeleHealth, Autism and Congenital Anomalies aimed to investigate whether a reanalysis of exomes from unsolved cases based on ClinVar annotations could establish additional diagnoses. We present the results of the “ClinVar low-hanging fruit” reanalysis, reasons for the failure of previous analyses, and lessons learned. Methods Data from the first 3576 exomes (1522 probands and 2054 relatives) collected from European Reference Network for Intellectual disability, TeleHealth, Autism and Congenital Anomalies was reanalyzed by the Solve-RD consortium by evaluating for the presence of single-nucleotide variant, and small insertions and deletions already reported as (likely) pathogenic in ClinVar. Variants were filtered according to frequency, genotype, and mode of inheritance and reinterpreted. Results We identified causal variants in 59 cases (3.9%), 50 of them also raised by other approaches and 9 leading to new diagnoses, highlighting interpretation challenges: variants in genes not known to be involved in human disease at the time of the first analysis, misleading genotypes, or variants undetected by local pipelines (variants in off-target regions, low quality filters, low allelic balance, or high frequency). Conclusion The “ClinVar low-hanging fruit” analysis represents an effective, fast, and easy approach to recover causal variants from exome sequencing data, herewith contributing to the reduction of the diagnostic deadlock

Role of barrage fishponds in the dynamic of micropollutants in headwater streams

En Lorraine, environ 7000 ha d’étangs sont exploités pour la production piscicole. Le présent travail a été consacré à la compréhension des mécanismes de transfert des micropolluants dans les étangs en mettant l'accent sur trois questions : (1) évaluer l'ampleur de la contamination métallique des étangs (n=45) ; (2) évaluer l'influence des étangs (n=3) sur les concentrations, le risque de toxicité et les flux de pesticides; (3) évaluer l'importance relative des voies de transfert des PCB vers le poisson. (1) Les enrichissements calculés soulignent des contaminations généralement faibles à modérés à l’exception des étangs localisés dans la Vôge et de deux étangs localisés dans la Woëvre. Cet enrichissement est plus prononcé pour le Cd et semble être lié à la richesse du sédiment en matière organique et carbonates (perte au feu). (2) Dans les cours d’eau de tête de bassin versant sur lesquels s’inscrivent ces trois étangs de barrage, les concentrations les plus élevées étaient généralement réduites de plus de 90% entre l'amont et l'aval de l'étang. Le risque de toxicité, évalué par la méthode de l'unité toxique, était atténué en aval des étangs. Lorsqu’on considère les flux de pesticides, les résultats obtenus suggèrent que, selon les substances considérées, les charges en pesticides sont réduites de 10 à 100% entre l'amont et l'aval de l'étang. (3) Les résultats montrent que le sédiment contaminé n’a pas d’impact sur la biodisponibilité orale des trois congénères de PCB chez la carpe commune. L’effet géosorbant du sédiment, qui explique son rôle de réservoir environnemental de PCB, paraît insuffisant dans les conditions du tractus digestif de la carpe commune, pour éviter un transfert vers le poissonIn the Lorraine Region, about 7,000 ha of ponds are exploited for fish production. The present work was dedicated to the understanding of micropollutants transfer mechanisms in freshwater fishponds focusing on three issues: (1) evaluate the extent of fishpond (n=45) exposure to trace metals (2) evaluate the influence of fishponds (n=3) on concentrations, potential toxicity and mass flows of pesticides; (3) evaluate the relative importance of transfer pathways of PCBs to fish. (1) The enrichments measured were generally low to moderate with the exception of the sites located in the Vôge and two sites located in the Woëvre. Enrichment was particularly high for Cd and seemed related to the loss of ignition. No relationship between enrichment and land use could however be observed. (2) High pesticide concentrations were generally reduced by more than 90% between upstream and downstream location. The risk of toxicity, evaluated under the toxic unit approach was attenuated downstream of the ponds. When considering the flow of pesticides, the results suggest that, depending on the substances in question, 10 to 100% of the loads of pesticides are retained in fishponds. (3) The oral transfer of polychlorinated biphenyls (PCBs 138, 153, and 180) from a contaminated sediment to a benthic fish (carp) was studied by the in vivo relative bioavailability method. The results show that the contaminated sediment has no effect on the oral bioavailability of the three PCB congeners in common carp. The geosorbing effect of sediment, which explains its role as an environmental reservoir of PCBs, seems insufficient under the conditions of the digestive tract of the common carp, to prevent transfer to fis

Rôle des étangs de barrage à vocation piscicole dans la dynamique des micropolluants en têtes de bassins versants

In the Lorraine Region, about 7,000 ha of ponds are exploited for fish production. The present work was dedicated to the understanding of micropollutants transfer mechanisms in freshwater fishponds focusing on three issues: (1) evaluate the extent of fishpond (n=45) exposure to trace metals (2) evaluate the influence of fishponds (n=3) on concentrations, potential toxicity and mass flows of pesticides; (3) evaluate the relative importance of transfer pathways of PCBs to fish. (1) The enrichments measured were generally low to moderate with the exception of the sites located in the Vôge and two sites located in the Woëvre. Enrichment was particularly high for Cd and seemed related to the loss of ignition. No relationship between enrichment and land use could however be observed. (2) High pesticide concentrations were generally reduced by more than 90% between upstream and downstream location. The risk of toxicity, evaluated under the toxic unit approach was attenuated downstream of the ponds. When considering the flow of pesticides, the results suggest that, depending on the substances in question, 10 to 100% of the loads of pesticides are retained in fishponds. (3) The oral transfer of polychlorinated biphenyls (PCBs 138, 153, and 180) from a contaminated sediment to a benthic fish (carp) was studied by the in vivo relative bioavailability method. The results show that the contaminated sediment has no effect on the oral bioavailability of the three PCB congeners in common carp. The geosorbing effect of sediment, which explains its role as an environmental reservoir of PCBs, seems insufficient under the conditions of the digestive tract of the common carp, to prevent transfer to fishEn Lorraine, environ 7000 ha d’étangs sont exploités pour la production piscicole. Le présent travail a été consacré à la compréhension des mécanismes de transfert des micropolluants dans les étangs en mettant l'accent sur trois questions : (1) évaluer l'ampleur de la contamination métallique des étangs (n=45) ; (2) évaluer l'influence des étangs (n=3) sur les concentrations, le risque de toxicité et les flux de pesticides; (3) évaluer l'importance relative des voies de transfert des PCB vers le poisson. (1) Les enrichissements calculés soulignent des contaminations généralement faibles à modérés à l’exception des étangs localisés dans la Vôge et de deux étangs localisés dans la Woëvre. Cet enrichissement est plus prononcé pour le Cd et semble être lié à la richesse du sédiment en matière organique et carbonates (perte au feu). (2) Dans les cours d’eau de tête de bassin versant sur lesquels s’inscrivent ces trois étangs de barrage, les concentrations les plus élevées étaient généralement réduites de plus de 90% entre l'amont et l'aval de l'étang. Le risque de toxicité, évalué par la méthode de l'unité toxique, était atténué en aval des étangs. Lorsqu’on considère les flux de pesticides, les résultats obtenus suggèrent que, selon les substances considérées, les charges en pesticides sont réduites de 10 à 100% entre l'amont et l'aval de l'étang. (3) Les résultats montrent que le sédiment contaminé n’a pas d’impact sur la biodisponibilité orale des trois congénères de PCB chez la carpe commune. L’effet géosorbant du sédiment, qui explique son rôle de réservoir environnemental de PCB, paraît insuffisant dans les conditions du tractus digestif de la carpe commune, pour éviter un transfert vers le poisso

L'expérience de la thèse en management. Regards croisés de jeunes docteurs

International audienceSi de nombreux supports d’accompagnement méthodologique existent, l’expérience de la thèse en elle-même est finalement peu documentée. Il s’agit ici de proposer un ensemble de contributions comme autant de retours d’expériences de la thèse par des jeunes docteurs. Cet ouvrage interroge à la fois l’idée même de faire une thèse, les difficultés à définir un sujet qui contribuera à la fois à la connaissance théorique et permettra de dégager des implications managériales actionnables. Il met en perspective les questionnements partagés par de nombreux doctorants ou futurs doctorants concernant la collecte et l’analyse de données, mais aussi l’entrée en communauté du chercheur. Il illustre ces thèmes par des retours d’expériences, sans pour autant renoncer à l’effort de conceptualisation qui permet de dépasser le simple statut de récit. Loin d’encourager à la standardisation des manuscrits de thèse, il invite à penser la diversité des approches et la pluralité de leurs finalités.Préface de Géraldine Schmidt et Hervé Laroche. Postface de Jérôme Caby.Coordonné par Hugo Gaillard, Julien Cloarec, Juliette Senn et Albane Grandazzi avec les contributions de Nour Alrabie, Christelle Aubert-Hassouni, Charles Aymard, Hajer Bachouche, Émilie Bonhoure, Angélique Breuillot, Julien Cloarec, Lucie Cortambert, Aurore Dandoy, Pauline de Becdelièvre, Zilacene Dekli, Kathleen Desveaud, Guillaume Do Vale, Juliane Engsig, Hugo Gaillard, Sophia Galière, Elise Goiseau, Albane Grandazzi, Raficka Hellal-Guendouzi, Alexis Laszczuk, Adrien Laurent, Claire Le Breton, Thomas Leclercq, Pierre Lescoat, Sarah Maire, Caroline Mattelin-Pierrard, Fabienne Perez, Sandra Renou, Émilie Ruiz, Juliette Senn, Margaux Vales, Pénélope Van den Bussche, Louis Vuarin, Lucie Wiart. Également, des grands entretiens avec Hervé Dumez, Markus Giesler, Jacques Igalens et Thomas Roulet

Évaluation des risques de contamination des eaux de surface par les produits phytosanitaires : application à un bassin versant viticole (projet PhytoCOTE)

Contaminations, environnements, santé et société. De l'évaluation des risques à l'action publique, Toulouse, , 04-/07/2018 - 06/07/2018International audienceL'évolution de la production qualitative viticole, s'est faite durant plusieurs décennies par l'usage souvent excessif de produits phytosanitaires. L'objectif était la lutte contre les cryptogames, les ravageurs des plantes et la gestion de la concurrence des adventices concernant les éléments minéraux, l'eau, l'espace de développement. Ces pesticides, faciles à utiliser et très efficaces, ont été appliqués durant cette période de façon systématique suivant des recommandations, généralement à l'encontre de considérations agronomiques et écologiques. Mais l'usage bénéfique de ces molécules pour les agrosystèmes trouve aussi ses conséquences dans la contamination des écosystèmes et particulièrement les hydrosystèmes, ainsi que sur la santé humaine. Le projet pluridisciplinaire PhytoCOTE (agronomie, hydrobiologie, chimie environnementale, écotoxicologie, économie) étudie l'usage des produits phytosanitaires dans les agrosystèmes viticoles, leurs transferts dans les écosystèmes connexes (eau, air, sol), leur bioaccumulation et leur potentiel toxique chez les organismes aquatiques. Le site d'étude est localisé dans le Blayais, région viticole située sur la rive droite de l'estuaire de la Gironde. Les recherches ont d'abord permis d'évaluer la contribution de parcelles viticoles aux risques de contamination des eaux de surface par les produits phytosanitaires utilisés en viticulture, en tenant compte de critères descriptifs du milieu (sols, relief, connectivité des parcelles par rapport aux cours d'eau) et des pratiques viticoles (pression phytosanitaire, degré d'enherbement des parcelles, zones tampons). Des cartes de ces risques au niveau du parcellaire ont pu être établies. Parallèlement, un suivi annuel de la variabilité spatio-temporelle des concentrations en pesticides a été mis en place dans les différents compartiments environnementaux. Le suivi des cours d'eau permanents repose notamment sur le déploiement de capteurs passifs POCIS (Polar Organic Chemical Integrative Samplers) classiques à une fréquence mensuelle et de prélèvements d'eau ponctuels (bi-mensuels). L'analyse de la cartographie des risques, de la concentration en pesticides, de la modélisation des modes de conduite viticole (conventionnel, agrobiologie, agroécologie,...) et du comportement décisionnel des agriculteurs face aux choix des méthodes de protection phytosanitaire, devrait permettre d'établir des scenarii de changements de ces pratiques. Le but in fine est de proposer aux viticulteurs des mesures concrètes de nature agro-écologiques pour une réduction des usages de ces produits phytosanitaires et d'analyser comment ces mesures pourraient être influencées par les politiques publiques

Le séquençage du génome du porc : apport des nouvelles technologies de séquençage à la génomique et la génétique porcine

Depuis une vingtaine d’années, l’évolution des technologies de biologie moléculaire a permis de révolutionner nos connaissances sur les génomes et, chez les animaux domestiques, d’améliorer significativement la sélection via des approches de sélection génomique (notamment chez les bovins laitiers). Parmi les développements technologiques majeurs, la mise au point d’une nouvelle génération de séquenceurs (NGS : Next Generation Sequencing) permet, depuis 2006, de déterminer la séquence individuelle de n’importe quel individu. En 2008, 100 fois plus rapidement que pour l’obtention de la première séquence du génome hu main et pour un coût également divisé par 100, une seconde séquence humaine a été publiée (Nature 452, no.7189 (2008) : 872 ‐ 876). Depuis, les données issues de cette technologie haut débit (HTS : High Throughput Sequencing) se sont accumulées pour de très nombreuses espèces et trouvent des applications dans des domaines de recherche fondamentale et appliquée extrêmement variés. En 2012, une première séquence du génome porcin a été produite dans le cadre d’un consortium international (Nature 491, no. 7424 (2012) : 393 ‐ 398). Le but de cette communication est de faire un état des lieux de l’apport de cette technologie à l’étude des génomes, plus particulièrement chez le porc. En s’appuyant sur les travaux réalisés chez d’autres espèces, une réflexion prospective sur l’impact de ces nouvelles données génomiques en génétique et en sélection porcine sera proposée.For twenty years, the development of new technologies in molecular biology have revolutionized our knowledge of genomes and, in livestock species, have significantly improved selection via new selection genomic approaches (essentially in dairy cattle). Among the major technologies, the development of a new generation of sequencers (NGS: Next Generation Sequencing) since 2006, allows the genome sequence of any individual to be acquired. In 2008, 100 times faster than for the first human genome sequence, and also for a cost divided by 100, a second human sequence was published (Nature 452, no.7189 (2008) : 872 ‐ 876). Since this period, the data from th is high throughput technology (HTS: High Throughput Sequencing) have been accumulated for many species and new extremely varied applications in fundamental and applied researches have been developed. In 2012, a first sequence of the pig genome was produced as part of an international consortium (Nature 491, no. 7424 (2012): 393 ‐ 3 98). The purpose of this communication is to make an inventory of the contribution of this technology to the study of genomes, particularly in pigs. Based on data obtained in other species, a prospective view on the impact of these new genomic data in genetics and pig breeding is also proposed