Comparing the intestinal transcriptome of Meishan and Large White piglets during late fetal development reveals genes involved in glucose and lipid metabolism and immunity as valuable clues of intestinal maturity

Background: Maturity of intestinal functions is critical for neonatal health and survival, but comprehensive description of mechanisms underlying intestinal maturation that occur during late gestation still remain poorly characterized. The aim of this study was to investigate biological processes specifically involved in intestinal maturation by comparing fetal jejunal transcriptomes of two representative porcine breeds (Large White, LW; Meishan, MS) with contrasting neonatal vitality and maturity, at two key time points during late gestation (gestational days 90 and 110). MS and LW sows inseminated with mixed semen (from breed LW and MS) gave birth to both purebred and crossbred fetuses. We hypothesized that part of the differences in neonatal maturity between the two breeds results from distinct developmental profiles of the fetal intestine during late gestation. Reciprocal crossed fetuses were used to analyze the effect of parental genome. Transcriptomic data and 23 phenotypic variables known to be associated with maturity trait were integrated using multivariate analysis with expectation of identifying relevant genes-phenotypic variable relationships involved in intestinal maturation. Results: A moderate maternal genotype effect, but no paternal genotype effect, was observed on offspring intestinal maturation. Four hundred and four differentially expressed probes, corresponding to 274 differentially expressed genes (DEGs), more specifically involved in the maturation process were further studied. In day 110-MS fetuses, Ingenuity® functional enrichment analysis revealed that 46% of DEGs were involved in glucose and lipid metabolism, cell proliferation, vasculogenesis and hormone synthesis compared to day 90-MS fetuses. Expression of genes involved in immune pathways including phagocytosis, inflammation and defense processes was changed in day 110-LW compared to day 90-LW fetuses (corresponding to 13% of DEGs). The transcriptional regulator PPARGC1A was predicted to be an important regulator of differentially expressed genes in MS. Fetal blood fructose level, intestinal lactase activity and villous height were the best predicted phenotypic variables with probes mostly involved in lipid metabolism, carbohydrate metabolism and cellular movement biological pathways. [b]Conclusions[/b]: Collectively, our findings indicate that the neonatal maturity of pig intestine may rely on functional development of glucose and lipid metabolisms, immune phagocyte differentiation and inflammatory pathways. This process may partially be governed by PPARGC1A

Identification of bound alcohols in soil humic acids by gas chromatography-mass spectrometry

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Integrative systems biology of wheat susceptibility to Fusarium graminearum uncovers a conserved gene regulatory network and identifies master regulators targeted by fungal core effectors

International audienceBackground Plant diseases are driven by an intricate set of defense mechanisms counterbalanced by the expression of host susceptibility factors promoted through the action of pathogen effectors. In spite of their central role in the establishment of the pathology, the primary components of plant susceptibility are still poorly understood and challenging to trace especially in plant-fungal interactions such as in Fusarium head blight (FHB) of bread wheat. Designing a system-level transcriptomics approach, we leveraged the analysis of wheat responses from a susceptible cultivar facing Fusarium graminearum strains of different aggressiveness and examined their constancy in four other wheat cultivars also developing FHB. Results In this study, we describe unexpected differential expression of a conserved set of transcription factors and an original subset of master regulators were evidenced using a regulation network approach. The dual-integration with the expression data of pathogen effector genes combined with database mining, demonstrated robust connections with the plant molecular regulators and identified relevant candidate genes involved in plant susceptibility, mostly able to suppress plant defense mechanisms. Furthermore, taking advantage of wheat cultivars of contrasting susceptibility levels, a refined list of 142 conserved susceptibility gene candidates was proposed to be necessary host’s determinants for the establishment of a compatible interaction. Conclusions Our findings emphasized major FHB determinants potentially controlling a set of conserved responses associated with susceptibility in bread wheat. They provide new clues for improving FHB control in wheat and also could conceivably leverage further original researches dealing with a broader spectrum of plant pathogens

Integrative systems biology of wheat susceptibility to Fusarium graminearum uncovers a conserved gene regulatory network and identifies master regulators targeted by fungal core effectors

Abstract Background Plant diseases are driven by an intricate set of defense mechanisms counterbalanced by the expression of host susceptibility factors promoted through the action of pathogen effectors. In spite of their central role in the establishment of the pathology, the primary components of plant susceptibility are still poorly understood and challenging to trace especially in plant-fungal interactions such as in Fusarium head blight (FHB) of bread wheat. Designing a system-level transcriptomics approach, we leveraged the analysis of wheat responses from a susceptible cultivar facing Fusarium graminearum strains of different aggressiveness and examined their constancy in four other wheat cultivars also developing FHB. Results In this study, we describe unexpected differential expression of a conserved set of transcription factors and an original subset of master regulators were evidenced using a regulation network approach. The dual-integration with the expression data of pathogen effector genes combined with database mining, demonstrated robust connections with the plant molecular regulators and identified relevant candidate genes involved in plant susceptibility, mostly able to suppress plant defense mechanisms. Furthermore, taking advantage of wheat cultivars of contrasting susceptibility levels, a refined list of 142 conserved susceptibility gene candidates was proposed to be necessary host’s determinants for the establishment of a compatible interaction. Conclusions Our findings emphasized major FHB determinants potentially controlling a set of conserved responses associated with susceptibility in bread wheat. They provide new clues for improving FHB control in wheat and also could conceivably leverage further original researches dealing with a broader spectrum of plant pathogens

Developpement de biomarqueurs sanguins pour évaluer la sensibilité des porcs à la chaleur

National audienceAvec l’environnement sanitaire, les paramètres climatiques sont les principaux facteurs environnementaux affectant les performances des porcs dans les grands bassins de production mondiaux localisés en particulier dans les régions tropicales (TROP) mais également en zones tempérées (TEMP). Les réponses de thermorégulation varient d’une race à une autre mais également d’un animal à l’autre à l’intérieur d’une même population. Dans le futur, cette variabilité pourrait être exploitée pour améliorer la robustesse des systèmes de production porcine face aux risques climatiques. Pour cela, il existe un enjeu fort au développement d’indicateurs pertinents pour quantifier précisément et, si possible rapidement, le niveau de sensibilité ou de robustesse à la chaleur. L’objectif de l’étude était d’utiliser le métabolome plasmatique (RMN) de porc mesuré en conditions TEMP pour prédire la sensibilité des descendants issus 10 familles de pères Large-White x Créole elevés en conditions TROP. La valeur génétique de chaque famille a été évaluée à partir de la mesure des performances (consommation d’aliment, poids vif et température rectale) de leurs descendants produits dans les deux environnements (#60 descendants/famille/ environnement). L’analyse du métabolome a été réalisée par spectroscopie RMN sur des échantillons prélévés à 23 semaines d’âge sur des animaux élevés en conditions TEMP (n=560). L’indice de sensibilité au climat TROP (Isens) a été évalué en calculant la valeur du t de Welsh de la variation de la valeur de chaque famille entre TEMP et TROP. Le modèle de prédiction a été établi sur les 4 familles extrêmes (2 familles sensibles et 2 familles robustes) avec Isens comme variable à prédire et le métabolome des descendants (n=223 porcs) comme variables prédictrices. Pour construire le modèle, nous avons utilisé la méthode de régression des moindres carrés partiels (PLS-DA) associée à une étape de sélection en utilisant la méthode LASSO. Le modèle de prédiction a été construit avec 19 prédicteurs sélectionnés par les 445 variables du métabolome et permettait de prédire la sensibilité au climat TROP avec un taux d’erreur de 22%. Ce modèle a été utilisé pour prédire le pourcentage de descendants classés comme sensibles (Psens) dans chacune des 10 familles de père. La très bonne corrélation entre Isens et Psens (r = 0,97) a validé notre modèle de prédiction. Sur la base de données utilisées dans cette étude, il semble être possible de classer les porcs selon leur sensibilité à la chaleur à partir d’une simple prise de sang réalisée dans des conditions TEMP. Samir Dou a bénéficié d’un contrat post-doctoral financé par la région Bretagne (Dispositif « Stratégie d'attractivité durable »). Le projet a été conduit dans le cadre du programme ANR PigHeaT (ANR-12-ADAP-0015). Les auteurs remercient le personnel de l’UE PTEA (Petit Bourg, Guadeloupe) et de l’UE GenESI (Magneraud) pour leur aide dans la réalisation de ce projet.</em

Neonatal microbiota diversity and structure modulate further resistance to post-weaning diarrhea in pigs

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Additional file 1 of Integrative systems biology of wheat susceptibility to Fusarium graminearum uncovers a conserved gene regulatory network and identifies master regulators targeted by fungal core effectors

Additional file 1: Table S1. Resume table of the statistical analysis performed on 'Recital' genes when facing one of the three different F. graminearum strains. Table S2. Expression patterns for each identified TF family that were FHB-responsive in 'Recital' facing one of the three F. graminearum strains. Table S3. A GO BP term enrichment results on the gene set under-expressed in FHB samples compared with controls. B GO BP term enrichment results on the gene set over-expressed in FHB samples compared with controls. Table S4. Resume Table of the master regulators identified in the TF regulatory network of the FHB responses. Table S5. Resume table of the identified known S genes

E2F signature is predictive for the pancreatic adenocarcinoma clinical outcome and sensitivity to E2F inhibitors, but not for the response to cytotoxic-based treatments

International audienceThe main goal of this study was to find out strategies of clinical relevance to classify patients with a pancreatic ductal adenocarcinoma (PDAC) for individualized treatments. In the present study a set of 55 patient-derived xenografts (PDX) were obtained and their transcriptome were analyzed by using an Affymetrix approach. A supervised bioinformatics-based analysis let us to classify these PDX in two main groups named E2F-highly dependent and E2F-lowly dependent. Afterwards their characterization by using a Kaplan-Meier analysis demonstrated that E2F high patients survived significantly less than E2F low patients (9.5 months vs. 16.8 months; p = 0.0066). Then we tried to establish if E2F transcriptional target levels were associated to the response to cytotoxic treatments by comparing the IC50 values of E2F high and E2F low cells after gemcitabine, 5-fluorouracil, oxaliplatin, docetaxel or irinotecan treatment, and no association was found. Then we identified an E2F inhibitor compound, named ly101-4B, and we observed that E2F-higly dependent cells were more sensitive to its treatment (IC50 of 19.4 ± 1.8 µM vs. 44.1 ± 4.4 µM; p = 0.0061). In conclusion, in this work we describe an E2F target expression-based classification that could be predictive for patient outcome, but more important, for the sensitivity of tumors to the E2F inhibitors as a treatment. Finally, we can assume that phenotypic characterization, essentially by an RNA expression analysis of the PDAC, can help to predict their clinical outcome and their response to some treatments when are rationally selected