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

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

Early microbiota composition influences susceptibility to post-weaning enteric disorders in pigs

Early microbiota composition influences susceptibility to post-weaning enteric disorders in pigs. Rowett-Inra Symposium - 2014 Isapp meeting. Gut Microbiology, from sequence to functio

^1HNMR-Based metabolomic profiling method to develop plasma biomarkers for sensitivity to chronic heat stress in growing pigs

<div><p>The negative impact of heat stress (HS) on the production performances in pig faming is of particular concern. Novel diagnostic methods are needed to predict the robustness of pigs to HS. Our study aimed to assess the reliability of blood metabolome to predict the sensitivity to chronic HS of 10 F1 (Large White × Creole) sire families (SF) reared in temperate (TEMP) and in tropical (TROP) regions (n = 56±5 offsprings/region/SF). Live body weight (BW) and rectal temperature (RT) were recorded at 23 weeks of age. Average daily feed intake (AFDI) and average daily gain were calculated from weeks 11 to 23 of age, together with feed conversion ratio. Plasma blood metabolome profiles were obtained by Nuclear Magnetic Resonance spectroscopy (^1HNMR) from blood samples collected at week 23 in TEMP. The sensitivity to hot climatic conditions of each SF was estimated by computing a composite index of sensitivity (I_<i>sens</i>) derived from a linear combination of <i>t</i> statistics applied to familial BW, ADFI and RT in TEMP and TROP climates. A model of prediction of sensitivity was established with sparse Partial Least Square Discriminant Analysis (<i>s</i>PLS-DA) between the two most robust SF (n = 102) and the two most sensitive ones (n = 121) using individual metabolomic profiles measured in TEMP. The sPLS-DA selected 29 buckets that enabled 78% of prediction accuracy by cross-validation. On the basis of this training, we predicted the proportion of sensitive pigs within the 6 remaining families (n = 337). This proportion was defined as the predicted membership of families to the sensitive category. The positive correlation between this proportion and I_<i>sens</i> (r = 0.97, P < 0.01) suggests that plasma metabolome can be used to predict the sensitivity of pigs to hot climate.</p></div

La matière grasse laitière et le probiotique L. fermentum CECT 5716 incorporés dans des formules infantiles programment la composition du microbiote et la fonction endocrine intestinale dans un modèle miniporc

National audienceIntroduction et but de l’étude : L’alimentation du nouveau-né joue un rôle déterminant dans la mise en place du microbiote intestinal et de ses interactions avec l’hôte, conditionnant la santé du futur adulte. Nous avons précédemment montré que l’incorporation de matière grasse laitière (MGL) associée ou non au probiotique Lactobacillus fermentum CECT 5716 (Lf) dans des formules infantiles (FI) modifie l’implantation du microbiote et la physiologie digestive chez le porcelet, utilisé comme modèle de l’Homme. Notre hypothèse est que ces modifications précoces pourraient avoir des conséquences sur la physiologie digestive et le métabolisme de l’adulte. Matériel et méthodes : Vingt-six miniporcs Yucatan ont été allaités avec une FI à base de matières grasses végétales (MGV), d’un mélange de MGV et de MGL (MGL), ou d’un mélange de MGV et de MGL supplémenté en Lf (MGL+Lf). Ils ont ensuite reçu un régime standard pendant 1 mois puis un régime hyperénergétique pendant 3 mois, induisant une insulinorésistance chez tous les animaux. La composition (séquençage 16S) et l’activité du microbiote dans le rectum (acides gras volatiles, métabolome), la fonction endocrine intestinale en conditions basale (extraction du GLP-1 caecal) et challengée (concentration plasmatique en GLP-1 après un repas test) ainsi que l’expression caecale des récepteurs aux acides gras (FFAR) ont été évaluées à l’âge de 5 mois. Résultats et Analyse statistique : La matrice lipidique de la FI et l’addition du probiotique Lf ont modulé la composition et l’activité du microbiote intestinal de l’adulte, avec des effets propres à l’ajout de MGL ou de Lf. La MGL a entraîné une augmentation de la concentration en glycérol tandis que le probiotique Lf a augmenté la concentration en propionate et diminué celle du 5 amino-valérate. En termes de composition du microbiote, l’ordre des Clostridiales a été particulièrement impacté par l’ajout de MGL (± Lf). Ces modifications de l’écosystème intestinal ont été associées à des changements de la fonction endocrine intestinale insulinotrope. L’addition de Lf dans la FI a ainsi augmenté la capacité sécrétoire intestinale de GLP-1 en conditions basale et challengée chez l’adulte. De plus, les corrélations positives (R>0,5 et pConclusion : L’incorporation de matière grasse laitière et de L. fermentum dans la formule infantile a modifié la composition du microbiote de l’adulte. La modulation du microbiote et de son activité métabolique, spécifiquement induite par L. fermentum, était associée à un effet bénéfique sur la capacité sécrétoire en GLP-1. Ces résultats soulignent l’importance de la composition des formules infantiles sur la santé métabolique à long terme