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 problème croissant chez le blé dur de la fusariose des épis causée par différentes espèces de Fusarium sp., une étude a été entreprise, avec le concours du Ministère chargé de l’Agriculture. Cette étude a permis d’évaluer la résistance de différentes sous-espèces de Triticum turgidum. Les populations contenant le plus d’individus résistants sont issues de la sous-espèce T. turgidum dicoccum. Une étude plus approfondie a permis de montrer cette résistance était de type 2 : faible progression des symptômes après la contamination d’un épillet par épi. Un géniteur, TRI2215, montre un niveau de résistance particulièrement intéressant, mais est très haut et très tardif, ce qui le rendra difficile à utiliser. C’est pourquoi une recherche de QTL a été entreprise sur ce géniteur. L’analyse des déterminants de l’agressivité des Fusarium confirme qu’elle vient en grande partie des mycotoxines. Différents composés phénoliques semblent aussi jouer un rôle dans la résistance de la plante. Une analyse qualitative de la flore fusarienne des épis a permis d’identifier six espèces majeures de Fusarium et de les associer avec les différentes mycotoxines, et qu’un genre proche, Microdochium, ne produisait pas de mycotoxines. Il a montré aussi que la quantité de mycotoxines dans un organe était proportionnelle à la quantité d’ADN du champignon dans l’organe

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 problème croissant chez le blé dur de la fusariose des épis causée par différentes espèces de Fusarium sp., une étude a été entreprise, avec le concours du Ministère chargé de l’Agriculture. Cette étude a permis d’évaluer la résistance de différentes sous-espèces de Triticum turgidum. Les populations contenant le plus d’individus résistants sont issues de la sous-espèce T. turgidum dicoccum. Une étude plus approfondie a permis de montrer cette résistance était de type 2 : faible progression des symptômes après la contamination d’un épillet par épi. Un géniteur, TRI2215, montre un niveau de résistance particulièrement intéressant, mais est très haut et très tardif, ce qui le rendra difficile à utiliser. C’est pourquoi une recherche de QTL a été entreprise sur ce géniteur. L’analyse des déterminants de l’agressivité des Fusarium confirme qu’elle vient en grande partie des mycotoxines. Différents composés phénoliques semblent aussi jouer un rôle dans la résistance de la plante. Une analyse qualitative de la flore fusarienne des épis a permis d’identifier six espèces majeures de Fusarium et de les associer avec les différentes mycotoxines, et qu’un genre proche, Microdochium, ne produisait pas de mycotoxines. Il a montré aussi que la quantité de mycotoxines dans un organe était proportionnelle à la quantité d’ADN du champignon dans l’organe

Pharmacoepidemiol Drug Saf

Purpose Upper gastrointestinal bleeding (UGIB) is a severe and frequent drug‐related event. In order to enable efficient drug safety alert generation in the French National Healthcare System database (SNDS), we assessed and calibrated empirically case‐based designs to identify drug associated with UGIB risk. Methods All cases of UGIB were extracted from SNDS (2009‐2014) using two definitions. Positive and negative drug controls were used to compare 196 self‐controlled case series (SCCS), case‐control (CC) and case‐population (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 30‐day risk window starting at exposure. The top‐performing 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 30‐day risk window has the potential to generate UGIB‐related 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 case‐based 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 drug‐related event. In order to enable efficient drug safety alert generation in the French National Healthcare System database (SNDS), we assessed and calibrated empirically case‐based designs to identify drug associated with UGIB risk. Methods All cases of UGIB were extracted from SNDS (2009‐2014) using two definitions. Positive and negative drug controls were used to compare 196 self‐controlled case series (SCCS), case‐control (CC) and case‐population (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 30‐day risk window starting at exposure. The top‐performing 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 30‐day risk window has the potential to generate UGIB‐related 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