A top-down systems biology view of microbiome-mammalian metabolic interactions in a mouse model

Symbiotic gut microorganisms (microbiome) interact closely with the mammalian host's metabolism and are important determinants of human health. Here, we decipher the complex metabolic effects of microbial manipulation, by comparing germfree mice colonized by a human baby flora (HBF) or a normal flora to conventional mice. We perform parallel microbiological profiling, metabolic profiling by 1H nuclear magnetic resonance of liver, plasma, urine and ileal flushes, and targeted profiling of bile acids by ultra performance liquid chromatography–mass spectrometry and short-chain fatty acids in cecum by GC-FID. Top-down multivariate analysis of metabolic profiles reveals a significant association of specific metabotypes with the resident microbiome. We derive a transgenomic graph model showing that HBF flora has a remarkably simple microbiome/metabolome correlation network, impacting directly on the host's ability to metabolize lipids: HBF mice present higher ileal concentrations of tauro-conjugated bile acids, reduced plasma levels of lipoproteins but higher hepatic triglyceride content associated with depletion of glutathione. These data indicate that the microbiome modulates absorption, storage and the energy harvest from the diet at the systems level

STAT5-and hypoxia-dependent upregulation of AXL

Internal tandem duplication in Fms-like tyrosine kinase 3 (FLT3-ITD) is the most frequent mutation observed in acute myeloid leukemia (AML) and correlates with poor prognosis. FLT3 tyrosine kinase inhibitors are promising for targeted therapy. Here, we investigated mechanisms dampening the response to the FLT3 inhibitor quizartinib, which is specific to the hematopoietic niche. Using AML primary samples and cell lines, we demonstrate that convergent signals from the hematopoietic microenvironment drive FLT3-ITD cell resistance to quizartinib through the expression and activation of the tyrosine kinase receptor AXL. Indeed, cytokines sustained phosphorylation of the transcription factor STAT5 in quizartinib-treated cells, which enhanced AXL expression by direct binding of a conserved motif in its genomic sequence. Likewise, hypoxia, another well-known hematopoietic niche hallmark, also enhanced AXL expression. Finally, in a xenograft mouse model, inhibition of AXL significantly increased the response of FLT3-ITD cells to quizartinib exclusively within a bone marrow environment. These data highlight a new bypass mechanism specific to the hematopoietic niche that hampers the response to quizartinib through combined upregulation of AXL activity. Targeting this signaling offers the prospect of a new therapy to eradicate resistant FLT3-ITD leukemic cells hidden within their specific microenvironment, thereby preventing relapses from FLT3-ITD clones

Cytoplasmic Incompatibility as a Means of Controlling Culex pipiens quinquefasciatus Mosquito in the Islands of the South-Western Indian Ocean

The use of the bacterium Wolbachia is an attractive alternative method to control vector populations. In mosquitoes, as in members of the Culex pipiens complex, Wolbachia induces a form of embryonic lethality called cytoplasmic incompatibility, a sperm-egg incompatibility occurring when infected males mate either with uninfected females or with females infected with incompatible Wolbachia strain(s). Here we explore the feasibility of the Incompatible Insect Technique (IIT), a species-specific control approach in which field females are sterilized by inundative releases of incompatible males. We show that the Wolbachia wPip(Is) strain, naturally infecting Cx. p. pipiens mosquitoes from Turkey, is a good candidate to control Cx. p. quinquefasciatus populations on four islands of the south-western Indian Ocean (La Réunion, Mauritius, Grande Glorieuse and Mayotte). The wPip(Is) strain was introduced into the nuclear background of Cx. p. quinquefasciatus mosquitoes from La Réunion, leading to the LR[wPip(Is)] line. Total embryonic lethality was observed in crosses between LR[wPip(Is)] males and all tested field females from the four islands. Interestingly, most crosses involving LR[wPip(Is)] females and field males were also incompatible, which is expected to reduce the impact of any accidental release of LR[wPip(Is)] females. Cage experiments demonstrate that LR[wPip(Is)] males are equally competitive with La Réunion males resulting in demographic crash when LR[wPip(Is)] males were introduced into La Réunion laboratory cages. These results, together with the geographic isolation of the four south-western Indian Ocean islands and their limited land area, support the feasibility of an IIT program using LR[wPip(Is)] males and stimulate the implementation of field tests for a Cx. p. quinquefasciatus control strategy on these islands

Dosage du polymorphisme : spectrométrie IRTF et chimiométrie. Application aux formes polymorphes du CL20 (Hexaazahexanitroisowurtzitane / HNIW).

HexaazahexaNitroIsoWurtzitane (or HNIW) hexanitred derivate, still called CL20, is a new highly energy molecule, which presents four polymorphic forms : α, β, γ and ε. Is the form ε most active and marketing stipulates to provide a product of which content of form ε that is to say higher than 95%, with estimate of the contents of the other forms as well as majority im-purity (pentanitred derivative). The aim of this work is on the one hand to characterize the four formes polymorphes, and on the other hand to develop, to optimize and validate a new quantitative analytical method to measure polymorphic composition of the CL20 by coupling IRTF (MIR) spectrometry/chemometric, respecting the technical and commercial require-ments, and transferable on factory site. The chemometric methods are used to conceive the experimentation and to process the experimental data necessary (calibration and validation).L'HexaazahexaNitroIsoWurtzitane (ou HNIW), dérivé hexanitré, encore appelé CL20, est une nouvelle molécule hautement énergétique, qui présente quatre formes polymorphes : α, β, γ et ε. La forme ε est la plus active et la commercialisation stipule de fournir un produit dont la teneur en forme ε soit supérieure à 95%, avec estimation des teneurs des autres formes ainsi que de l'impureté majoritaire (dérivé pentanitré). L'objet du présent travail est d'une part de caractériser les différentes formes polymorphes, et d'autre part de mettre au point, d'optimiser et de valider une méthode d'analyse quantitative du CL20 polymorphe par couplage spectro-métrie IRTF/chimiométrie, respectant les impératifs techniques et commerciaux et transférable sur site industriel. Les méthodes chimiométriques sont utilisées pour concevoir l'expérimentation et traiter l'information expérimentale nécessaire (étalonnage et validation)

Les Pathologies dues à Ctenocephalides felis et leurs prises en charge à l'officine chez le chat et chez l'homme

LYON1-BU Santé (693882101) / SudocSudocFranceF

Dosage du polymorphisme (spectrométrie IRTF et chimiométrie. Application aux formes polymorphes du CL20(Hexaazahexanitroisowurtzitane / HNIW))

L'HexaazahexaNitroIsoWurtzitane (ou HNIW), dérivé hexanitré, encore appelé CL20, est une nouvelle molécule hautement énergétique, qui présente quatre formes polymorphes : a, ß, g et . La forme est la plus active et la commercialisation stipule de fournir un produit dont la teneur en forme e soit supérieure à 95%, avec estimation des teneurs des autres formes ainsi que de l'impureté majoritaire (dérivé pentanitré). L'objet du présent travail est d'une part de caractériser les différentes formes polymorphes, et d'autre part de mettre au point, d'optimiser et de valider une méthode d'analyse quantitative du CL20 polymorphe par couplage spectrométrie IRTF/chimiométrie, respectant les impératifs techniques et commerciaux et transférable sur site industriel. Les méthodes chimiométriques sont utilisées pour concevoir l'expérimentation et traiter l'information expérimentale nécessaire (étalonnage et validation).LYON1-BU.Sciences (692662101) / SudocSudocFranceF

Development of quantitative analytical methods to measure the polymorphic composition of CL20 (Hexanitrohexaazaisowurtzitane - HNIW) with FTIR-NIR or FTIR-MIR spectroscopy using PLS regression

International audienceCL20 (HNIW=Hexanitrohexaazaisowurtzitane), is an energetic molecule that presents four polymorphs (called alpha (a), beta (beta), gamma (?), and epsilon (e)). Industry is focused to synthesize the e-form. For them, it is very important to get an analytical method to quantify the concentration of the e-form, which has the best energetic performance. The aim of this work is to develop a quantitative analytical method to measure the polymorphic composition of CL20 using FTIR (mid IR and near IR, MIR/NIR) spectroscopy with PLS regression

Occupation humaine et dynamique fluviale à Isle-Saint-Georges (Gironde).

.Actes du 37e colloque de l’AFEAFInternational audienc