17 research outputs found
P04-36. HIV-1-speficic antibody dependant cellular cytotoxicity (ADCC) médiated by primary NK cells
International audiencen.
P11-16. Transfer of HIV-1 from Langerhans and interstitial dendritic cells to T lymphocytes: protection mediated by antibodies?
International audiencen.
Caractérisation de sources de résistance à la fusariose chez le blé dur
National audienceFacing the increasing problem of Fusarium head blight with durum wheat caused by different species of Fusarium, a study was undertaken with the help of the Ministry in charge for agriculture. This study made it possible to assess the resistance of different sub-species of Triticum turgidum. The populations with the most resistant accessions belong to the sub-species T. turgidum dicoccum. Going deeper into this study showed that this resistance was a type 2 one: slow progression of necrosis after contamination of one spikelet per spike. One accession, TRI2215, exhibited very high level of resistance, but it is very high and very late accession, this will make this accession difficult to be used in breeding. This justifies a QTL search for Fusarium resistance. The analysis of the determinant for Fusarium aggressiveness confirmed that a great part was linked with the production of mycotoxins. Several phenol compounds seemed to play a part in the resistance of the plant. A qualitative analysis of the Fusarium flora on the spikes allowed identifying six major Fusarium species and to associate them with the different mycotoxins. A close genus, Microdochium, did not produce mycotoxins. We also showed that the amount of mycotoxins in an organ was related to the fungus DNA in the organ.Face au problĂšme croissant chez le blĂ© dur de la fusariose des Ă©pis causĂ©e par diffĂ©rentes espĂšces de Fusarium sp., une Ă©tude a Ă©tĂ© entreprise, avec le concours du MinistĂšre chargĂ© de lâAgriculture. Cette Ă©tude a permis dâĂ©valuer la rĂ©sistance de diffĂ©rentes sous-espĂšces de Triticum turgidum. Les populations contenant le plus dâindividus rĂ©sistants sont issues de la sous-espĂšce T. turgidum dicoccum. Une Ă©tude plus approfondie a permis de montrer cette rĂ©sistance Ă©tait de type 2 : faible progression des symptĂŽmes aprĂšs la contamination dâun Ă©pillet par Ă©pi. Un gĂ©niteur, TRI2215, montre un niveau de rĂ©sistance particuliĂšrement intĂ©ressant, mais est trĂšs haut et trĂšs tardif, ce qui le rendra difficile Ă utiliser. Câest pourquoi une recherche de QTL a Ă©tĂ© entreprise sur ce gĂ©niteur. Lâanalyse des dĂ©terminants de lâagressivitĂ© des Fusarium confirme quâelle vient en grande partie des mycotoxines. DiffĂ©rents composĂ©s phĂ©noliques semblent aussi jouer un rĂŽle dans la rĂ©sistance de la plante. Une analyse qualitative de la flore fusarienne des Ă©pis a permis dâidentifier six espĂšces majeures de Fusarium et de les associer avec les diffĂ©rentes mycotoxines, et quâun genre proche, Microdochium, ne produisait pas de mycotoxines. Il a montrĂ© aussi que la quantitĂ© de mycotoxines dans un organe Ă©tait proportionnelle Ă la quantitĂ© dâADN du champignon dans lâorgane
Caractérisation de sources de résistance à la fusariose chez le blé dur
National audienceFacing the increasing problem of Fusarium head blight with durum wheat caused by different species of Fusarium, a study was undertaken with the help of the Ministry in charge for agriculture. This study made it possible to assess the resistance of different sub-species of Triticum turgidum. The populations with the most resistant accessions belong to the sub-species T. turgidum dicoccum. Going deeper into this study showed that this resistance was a type 2 one: slow progression of necrosis after contamination of one spikelet per spike. One accession, TRI2215, exhibited very high level of resistance, but it is very high and very late accession, this will make this accession difficult to be used in breeding. This justifies a QTL search for Fusarium resistance. The analysis of the determinant for Fusarium aggressiveness confirmed that a great part was linked with the production of mycotoxins. Several phenol compounds seemed to play a part in the resistance of the plant. A qualitative analysis of the Fusarium flora on the spikes allowed identifying six major Fusarium species and to associate them with the different mycotoxins. A close genus, Microdochium, did not produce mycotoxins. We also showed that the amount of mycotoxins in an organ was related to the fungus DNA in the organ.Face au problĂšme croissant chez le blĂ© dur de la fusariose des Ă©pis causĂ©e par diffĂ©rentes espĂšces de Fusarium sp., une Ă©tude a Ă©tĂ© entreprise, avec le concours du MinistĂšre chargĂ© de lâAgriculture. Cette Ă©tude a permis dâĂ©valuer la rĂ©sistance de diffĂ©rentes sous-espĂšces de Triticum turgidum. Les populations contenant le plus dâindividus rĂ©sistants sont issues de la sous-espĂšce T. turgidum dicoccum. Une Ă©tude plus approfondie a permis de montrer cette rĂ©sistance Ă©tait de type 2 : faible progression des symptĂŽmes aprĂšs la contamination dâun Ă©pillet par Ă©pi. Un gĂ©niteur, TRI2215, montre un niveau de rĂ©sistance particuliĂšrement intĂ©ressant, mais est trĂšs haut et trĂšs tardif, ce qui le rendra difficile Ă utiliser. Câest pourquoi une recherche de QTL a Ă©tĂ© entreprise sur ce gĂ©niteur. Lâanalyse des dĂ©terminants de lâagressivitĂ© des Fusarium confirme quâelle vient en grande partie des mycotoxines. DiffĂ©rents composĂ©s phĂ©noliques semblent aussi jouer un rĂŽle dans la rĂ©sistance de la plante. Une analyse qualitative de la flore fusarienne des Ă©pis a permis dâidentifier six espĂšces majeures de Fusarium et de les associer avec les diffĂ©rentes mycotoxines, et quâun genre proche, Microdochium, ne produisait pas de mycotoxines. Il a montrĂ© aussi que la quantitĂ© de mycotoxines dans un organe Ă©tait proportionnelle Ă la quantitĂ© dâADN du champignon dans lâorgane
Pharmacoepidemiol Drug Saf
Purpose Upper gastrointestinal bleeding (UGIB) is a severe and frequent drugârelated event. In order to enable efficient drug safety alert generation in the French National Healthcare System database (SNDS), we assessed and calibrated empirically caseâbased designs to identify drug associated with UGIB risk. Methods All cases of UGIB were extracted from SNDS (2009â2014) using two definitions. Positive and negative drug controls were used to compare 196 selfâcontrolled case series (SCCS), caseâcontrol (CC) and caseâpopulation (CP) design variants. Each variant was evaluated in a 1/10th population sample using area under the receiver operating curve (AUC) and mean square error (MSE). Parameters that had major impacts on results were identified through logistic regression. Optimal designs were replicated in the unsampled population. Results Using a specific UGIB definition, AUCs ranged from 0.64 to 0.80, 0.44 to 0.61 and 0.50 to 0.67, for SCCS, CC and CP, respectively. MSE ranged from 0.07 to 0.39, 0.83 to 1.33 and 1.96 to 4.6, respectively. Univariate regressions showed that high AUCs were achieved with SCCS with multiple drug adjustment and a 30âday risk window starting at exposure. The topâperforming SCCS variant in the unsampled population yielded an AUC = 0.84 and MSE = 0.14, with 10/36 negative controls presenting significant estimates. Conclusions SCCS adjusting for multiple drugs and using a 30âday risk window has the potential to generate UGIBârelated alerts in the SNDS and hypotheses on its potential population impact. Negative control implementation highlighted that low systematic error was generated but that protopathic bias and confounding by indication remained unaddressed issues
Empirical assessment of caseâbased methods for identification of drugs associated with upper gastrointestinal bleeding in the French National Healthcare System database ( SNDS
Purpose Upper gastrointestinal bleeding (UGIB) is a severe and frequent drugârelated event. In order to enable efficient drug safety alert generation in the French National Healthcare System database (SNDS), we assessed and calibrated empirically caseâbased designs to identify drug associated with UGIB risk. Methods All cases of UGIB were extracted from SNDS (2009â2014) using two definitions. Positive and negative drug controls were used to compare 196 selfâcontrolled case series (SCCS), caseâcontrol (CC) and caseâpopulation (CP) design variants. Each variant was evaluated in a 1/10th population sample using area under the receiver operating curve (AUC) and mean square error (MSE). Parameters that had major impacts on results were identified through logistic regression. Optimal designs were replicated in the unsampled population. Results Using a specific UGIB definition, AUCs ranged from 0.64 to 0.80, 0.44 to 0.61 and 0.50 to 0.67, for SCCS, CC and CP, respectively. MSE ranged from 0.07 to 0.39, 0.83 to 1.33 and 1.96 to 4.6, respectively. Univariate regressions showed that high AUCs were achieved with SCCS with multiple drug adjustment and a 30âday risk window starting at exposure. The topâperforming SCCS variant in the unsampled population yielded an AUC = 0.84 and MSE = 0.14, with 10/36 negative controls presenting significant estimates. Conclusions SCCS adjusting for multiple drugs and using a 30âday risk window has the potential to generate UGIBârelated alerts in the SNDS and hypotheses on its potential population impact. Negative control implementation highlighted that low systematic error was generated but that protopathic bias and confounding by indication remained unaddressed issues
Fine-tuning and autoregulation of the intestinal determinant and tumor suppressor homeobox gene CDX2 by alternative splicing
On the basis of phylogenetic analyses, we uncovered a variant of the CDX2 homeobox gene, a major regulator of the development and homeostasis of the gut epithelium, also involved in cancer. This variant, miniCDX2, is generated by alternative splicing coupled to alternative translation initiation, and contains the DNA-binding homeodomain but is devoid of transactivation domain. It is predominantly expressed in crypt cells, whereas the CDX2 protein is present in crypt cells but also in differentiated villous cells. Functional studies revealed a dominant-negative effect exerted by miniCDX2 on the transcriptional activity of CDX2, and conversely similar effects regarding several transcription-independent functions of CDX2. In addition, a regulatory role played by the CDX2 and miniCDX2 homeoproteins on their pre-mRNA splicing is displayed, through interactions with splicing factors. Overexpression of miniCDX2 in the duodenal Brunner glands leads to the expansion of the territory of these glands and ultimately to brunneroma. As a whole, this study characterized a new and original variant of the CDX2 homeobox gene. The production of this variant represents not only a novel level of regulation of this gene, but also a novel way to fine-tune its biological activity through the versatile functions exerted by the truncated variant compared to the full-length homeoprotein. This study highlights the relevance of generating protein diversity through alternative splicing in the gut and its diseases