National Research Institute for Agriculture, Food and Environment

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    Efficacy of HE4, CA125, risk of malignancy index and risk of ovarian malignancy index to detect ovarian cancer in women with presumed benign ovarian tumours: a prospective, multicentre trial

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    Presumed benign ovarian tumours (PBOT) are defined by the International Ovarian Tumour Analysis (IOTA) group, without suspected sonographic criteria of cancer, without ascites or metastasis. The aim is to evaluate the efficacy of human epididymis protein 4 (HE4), cancer antigen 125 (CA125), the risk of malignancy index (RMI) and the risk of ovarian malignancy index (ROMA) to predict ovarian cancer in women with PBOT. Methods: It is a prospective, observational, multicentre, laboratory-based study including women with PBOT in four hospitals from 11 May 2015 through 12 May 2016. Preoperative CA125 and HE4 plasma levels were measured for all women. The primary endpoint was the specificity of CA125 and HE4 for diagnosing ovarian cancer. The main secondary endpoints were specificity and likelihood ratio of RMI, ROMA and tumours markers. Results: Two hundred and fifty patients were initially enrolled and 221 patients were finally analysed, including 209 benign ovarian tumours (94.6%) and 12 malignant ovarian tumours (5.4%). The malignant group had significantly higher mean values of HE4, CA125, RMI and ROMA compared to the benign group (p < 0.001). Specificity was significantly higher using a combination of HE4 and CA125 (99.5%) compared to either HE4 or CA125 alone (90.4% and 91.4%, respectively, p < 0.001). Moreover, the positive likelihood ratio for combination HE4 and CA125 was significantly higher (104.5; 95% CI 13.6–800.0) compared to HE4 alone (5.81; 95% CI 2.83–11.90) or CA125 alone (6.97; 95% CI 3.91–12.41). Conclusions: The combination of HE4 and CA125 represents the best tool to predict the risk of ovarian cancer in patients with a PBO

    CPlantBox, a whole plant modelling framework for the simulation of water and carbon related processes

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    The interaction between carbon and flows within the plant is at the center of most growth and developmental processes. Understanding how these fluxes influence each other, and how they respond to heterogeneous environmental conditions, is important to answer diverse questions in forest, agriculture and environmental sciences. However, due to the high complexity of the plant-environment system, specific tools are needed to perform such quantitative analyses.Here we present CPlantBox, full plant modelling framework based on the root system model CRootBox. CPlantbox is capable of simulating the growth and development of a variety of plant architectures (root and shoot). In addition, the flexibility of CPlantBox enables its coupling with external modeling tools. Here, we connected it to an existing mechanistic model of water and carbon flows in the plant, PiafMunch.The usefulness of the CPlantBox modelling framework is exemplified in four case studies. Firstly, we illustrate the range of plant structures that can be simulated using CPlantBox. In the second example, we simulated diurnal carbon and water flows, which corroborates published experimental data. In the third case study, we simulated impacts of heterogeneous environment on carbon and water flows. Finally, we showed that our modelling framework can be used to fit phloem pressure and flow speed to (published) experimental data.The CPlantBox modelling framework is open-source, highly accessible and flexible. Its aim is to provide a quantitative framework for the understanding of plant-environment interaction

    Life history traits of ooencyrtus pityocampae (Hymenoptera: Encyrtidae) reared on halyomorpha halys eggs (Hemiptera: Pentatomidae)

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    The brown marmorated stink bug, Halyomorpha halys Stål (Hemiptera: Pentatomidae) originates from Asia and has recently disseminated to America and Europe, where it is considered as an invasive pest of various crops. Developing biological control strategies is necessary, and egg parasitoids are among the best candidates. In this context, the objective of this study was to evaluate the fitness of the egg parasitoid Ooencyrtus pityocampae Mercet (Hymenoptera: Encyrtidae) reared on H. halys eggs, under laboratory conditions. We specifically investigated the impact of host age, host density and length of exposure on O. pityocampae life history traits. Host age × host density and host age × length of exposure affected the performance of O. pityocampae. The optimal emergence rate of the parasitoid was obtained from one-day-old H. halys eggs and 3 days of exposure. The parasitoid embryonic development ranged from 17.1 to 18.3 days. The mean longevity of O. pityocampae was 44.1 days. This species reproduces by thelytokous parthenogenesis and the female parasitoid produced an average of 42.6 progeny during their lifespan. Pre-oviposition, oviposition and post-oviposition periods were 1.9 days, 18.8 days and 24.8 days, respectively. These results suggest that H. halys is a suitable host for O. pityocampae, and may help for the development of a pest-management strategy against H. halys

    Effet pléiotrope de la mutation R96C dans le gène SOCS2 chez la brebis laitière

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    Dans cette thèse, nous nous sommes intéressée à une mutation dans le gène SOCS2(Suppressor Of Cytokine Signaling 2) dont l’effet est pléiotrope, c’est-à-dire qu’il concerne plusieurs caractères d’intérêt chez la brebis laitière Lacaune. Cette mutation estdéfavorable pour la résistance aux mammites (inflammation de la mamelle), et favorable pour les caractères de croissance et de productionlaitière. Située dans le domaine de liaison très conservé de la protéine SOCS-2, cette mutation ponctuelle (SNP:Single Nucleotide Polymorphism) entraîne la perte de fonctionnalité de la protéine qui est impliquée dans une voie majeure de signalisation chez les mammifères, la voie JAK (Janus Kinase) / STAT (Signal Transducer and Activator of Transcription), régulant un large spectre de cytokines et de facteurs de croissance.Le premier objectif de cette thèse était de proposer la prise en compte de cette mutation dans le contexte de la sélection génomique dans la race Lacaune. Les méthodes d’évaluation pondérées, et l’ajout du SNP SOCS2parmi les marqueurs de la puce, ont apporté des gains de précisions sur les prédictions (respectivement +3,99% et +0,26% en moyenne), laissant envisager la possibilité d’unesélection plus efficace. La méthode Gene Contentétait également intéressante car elle a permis de dissocier la valeur génétique due au gène SOCS2de celle provenant des autres gènes (polygène). Ainsi nous avons montré que la sélection actuelle en race Lacaune permet de diminuer la fréquence de l’allèle défavorable SOCS2tout en améliorant la résistance aux mammites expliquée par le reste du génome.Le deuxième objectif était d’étudier les effets de SOCS-2 sur des caractères d’intérêt non évalués jusqu’à présent: statut infectieux des mamelles et reproduction chez la femelle, et croissance des mâles. Des études d’association avec une puce de 960 SNP, dont le SNP SOCS2, ont confirmé l’effet de SOCS2sur la production laitière et sur l’inflammation mammaire, et ont montré un effet direct sur l’infection à l’aide de nouveaux phénotypes fins (bactériologie, examens cliniques). Des modèles linéaires ont montréque la mutation SOCS2était associée à une augmentation de poids chez les jeunes mâles (+1,5%), comme cela avait été observé chez la brebis, et àune diminution du taux de réussite à l’insémination artificielle chez les brebis (+1,3 fois de risque d’échec), sans effet sur la prolificité. Ces résultats marquants et originaux sur la reproduction ouvrent la voie à des analyses complémentaires pour déterminer notamment à quelstade biologique (ovulation, fécondation, implantation embryonnaire, etc.) la protéine SOCS-2 pourrait intervenir.Le dernier objectif était de déterminer le rôle de la protéine SOCS-2 dans les mécanismes biologiques sous-jacents de l’immunité grâce à l’étude de la réponse de 14 brebis porteuses et non porteuses de la mutation à l’état homozygote dans le cadre d’une infection intra-mammaire par un Staphylococcus aureus. L’ensemble des brebis a présenté deux pics de recrutement de cellules immunitaires versla mamelle à 20 et 88 heures post-inoculation (T20 et T88). Une analyse différentielle des gènes exprimés a confirmé une modification du transcriptome à partir de T16 en lien avec l’activation du système immunitaire,des voies de réparation de l’ADN et d’apoptose cellulaire. Les brebis portant la mutation SOCS2se sont différenciées des brebis sauvages, par une réaction clinique accrue à T56 et une différence de recrutement de lymphocytes T au moment des pics inflammatoires. A T56, un total de 177 gènes était différentiellement exprimé entre les deux génotypes. Une analyse fonctionnelle de ces gènes, et l’intégration entre l’expression génique et les phénotypes, suggèrent que la mutation conduit à une sur activation des voies de transmission de signal et derégulation (interférons, STAT3) avec un impact délétère sur l’état clinique des brebis.In this PhD thesis, we investigated a mutation in the SOCS2gene (Suppressor Of Cytokine Signaling 2) with a pleiotropic effect, i.e.it affects several traits of interest in the Lacaune dairy sheep. This mutation is unfavorable for mastitis resistance (udderinflammation), and favorable for growth and milk production traits.This point mutation (SNP -Single Nucleotide Polymorphism), located in the highly conserved binding domain of the SOCS-2 protein,causes the loss of functionality of the protein that is involved in a major signaling pathway in mammals:the JAK(Janus Kinase) / STAT (Signal Transducer and Activator of Transcription) pathway, regulating a large spectrum of cytokines and growth factors.The first objective of this PhD thesis was to provide a basis for considering this mutation in the context of genomic selection in the Lacaune breed. Weighted evaluation methods, and the addition of the SOCS2SNP among the chip markers, brought gains in accuracy on predictions (+3.99% and +0.26% respectively on average), suggesting the possibility of more efficient selection. The Gene Contentmethod was also interesting because it alloweddissociatingthe genetic value due to the SOCS2gene from that of the other genes (polygene). Thus, we have shown that the current selection in Lacaune breed allows reducing the frequency of the unfavorable SOCS2allele while improving the resistance to mastitis explained by the remaining part of the genome.The second objective was to study the effects of SOCS2on traits of interest not yet investigated: udder infection status and reproduction in females, and growth in males. Association studies with a 960 SNP chip, including SOCS2SNP, confirmed the effect of SOCS2on milk production and mammary inflammation, and showed a direct effect on infection using new fine phenotypes (bacteriology, clinical examinations). Linear models showed that the SOCS2mutation was associated withan increase in weight in young males (+1.5%), as observed in ewes, and a decrease in the artificial insemination success rate in ewes (+1.3 times the risk of failure), with no effect on prolificacy. These striking and original results on reproduction pave the way for further analyses to determine in particular at what biological stage (ovulation, fecundation, embryonic implantation, etc.) the SOCS-2 protein could be involved.The last objective was to determine the role of the SOCS-2 protein in the underlying biological mechanisms of immunity by investigating the response of 14 homozygous carrier and non-carrier ewes to intramammary infection by Staphylococcus aureus. All ewes developed two peaks of immune cell recruitment to the udder at 20 and 88 hours post-inoculation (T20 and T88). Differential analysis of the expressed genes confirmed a modification of the transcriptome from T16 related to the activation of the immune system, the DNA repair and the cellular apoptosis pathways. Ewes carrying the SOCS2mutation were distinguished from wild ewes by an increased clinical response at T56 and a difference in T lymphocyte recruitment at the time of the inflammatory peaks. At T56, a total of 177 genes were differentially expressed between the two genotypes. A functional analysis of these genes, and the integration between gene expression and phenotypes, suggest that the mutation leads to an over activation of signal transmission and regulatory pathways (interferons, STAT3) with a deleterious impact on the clinical status of ewe

    Optimization and evaluation of a non-invasive tool for peste des petits ruminants surveillance and control

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    Peste des petits ruminants (PPR) is a highly contagious and devastating viral disease affecting mainly sheep and goats, but also a large number of wild species within the order Artiodactyla. A better understanding of PPR transmission dynamics in multi-host systems is necessary to efficiently control the disease, in particular where wildlife and livestock co-occur. Notably, the role of wildlife in PPR epidemiology is still not clearly understood. Non-invasive strategies to detect PPR infection without the need for animal handling could greatly facilitate research on PPR epidemiology and management of the disease in atypical hosts and in complex field situations. Here, we describe optimized methods for the direct detection of PPR virus genetic material and antigen in fecal samples. We use these methods to determine the detection window of PPR in fecal samples, and compare the sensitivity of these methods to standard invasive sampling and PPR diagnostic methods using field samples collected at a wildlife-livestock interface in Africa. Our results show that quantitative reverse transcription PCR (RT-QPCR) amplification of PPRV from fecal swabs has good sensitivity in comparison to ocular swabs. Animals infected by PPRV could be identified relatively early on and during the whole course of infection based on fecal samples using RT-QPCR. Partial gene sequences could also be retrieved in some cases, from both fecal and ocular samples, providing important information about virus origin and relatedness to other PPRV strains. Non-invasive strategies for PPRV surveillance could provide important data to fill major gaps in our knowledge of the multi-host PPR epidemiology

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