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Projet Termitofuel: les termites et leurs symbiontes pour mieux valoriser la biomasse ligno-cellulosique

L’exploitation actuelle de la biomasse ligno-cellulosique, extrêmement abondante sur Terre, est liée à la production de déchets relativement peu valorisables. C’est pourquoi le projet TERMITOFUEL étudie la digestion du bois chez les termites, grâce à une approche pluridisciplinaire, en vue d’améliorer la production de bioéthanol de seconde génération. Au sein de l’Unité d’Entomologie Fonctionnelle et Evolutive, l’approche protéomique est employée afin d’identifier les micro-organismes présents dans le tube digestif des termites et caractériser les activités enzymatiques

Glucose-derived spiro-isoxazolines are anti-hyperglycemic agents against type 2 diabetes through glycogen phosphorylase inhibition

International audienceGlycogen phosphorylase (GP) is a target for the treatment of hyperglycaemia in the context of type 2 diabetes. This enzyme is responsible for the depolymerization of glycogen into glucose thereby affecting the levels of glucose in the blood stream. Twelve new d-glucopyranosylidene-spiro-isoxazolines have been prepared from O-peracylated exo-D-glucals by regio- and stereoselective 1,3-dipolar cycloaddition of nitrile oxides generated in situ by treatment of the corresponding oximes with bleach. This mild and direct procedure appeared to be applicable to a broad range of substrates. The corresponding O-unprotected spiro-isoxazolines were evaluated as glycogen phosphorylase (GP) inhibitors and exhibited IC50 values ranging from 1 to 800 μM. Selected inhibitors were further evaluated in vitro using rat and human hepatocytes and exhibited significant inhibitory properties in the primary cell culture. Interestingly, when tested with human hepatocytes, the tetra-O-acetylated spiro-isoxazoline bearing a 2-naphthyl residue showed a much lower IC50 value (2.5 μM), compared to that of the O-unprotected analog (19.95 μM). The most promising compounds were investigated in Zucker fa/fa rat model in acute and sub-chronic assays and decreased hepatic glucose production, which is known to be elevated in type 2 diabetes. This indicates that glucose-based spiro-isoxazolines can be considered as anti-hyperglycemic agents in the context of type 2 diabetes

Gut Pathology and Responses to the Microsporidium Nosema ceranae in the Honey Bee Apis mellifera

The microsporidium Nosema ceranae is a newly prevalent parasite of the European honey bee (Apis mellifera). Although this parasite is presently spreading across the world into its novel host, the mechanisms by it which affects the bees and how bees respond are not well understood. We therefore performed an extensive characterization of the parasite effects at the molecular level by using genetic and biochemical tools. The transcriptome modifications at the midgut level were characterized seven days post-infection with tiling microarrays. Then we tested the bee midgut response to infection by measuring activity of antioxidant and detoxification enzymes (superoxide dismutases, glutathione peroxidases, glutathione reductase, and glutathione-S-transferase). At the gene-expression level, the bee midgut responded to N. ceranae infection by an increase in oxidative stress concurrent with the generation of antioxidant enzymes, defense and protective response specifically observed in the gut of mammals and insects. However, at the enzymatic level, the protective response was not confirmed, with only glutathione-S-transferase exhibiting a higher activity in infected bees. The oxidative stress was associated with a higher transcription of sugar transporter in the gut. Finally, a dramatic effect of the microsporidia infection was the inhibition of genes involved in the homeostasis and renewal of intestinal tissues (Wnt signaling pathway), a phenomenon that was confirmed at the histological level. This tissue degeneration and prevention of gut epithelium renewal may explain early bee death. In conclusion, our integrated approach not only gives new insights into the pathological effects of N. ceranae and the bee gut response, but also demonstrate that the honey bee gut is an interesting model system for studying host defense responses

Developing an acoustic-phonetic characterization of dysarthric speech in French

- ISBN: 2-9517408-6-7 - Domaines: Phonetic Databases, Phonology, Person IdentificationInternational audienceThis paper presents the rationale, objectives and advances of an on-going project (the DesPho-APaDy project funded by the French National Agency of Research) which aims to provide a systematic and quantified description of French dysarthric speech, over a large population of patients and three dysarthria types (related to the parkinson's disease, the Amyotrophic Lateral Sclerosis disease, and a pure cerebellar alteration). The two French corpora of dysarthric patients, from which the speech data have been selected for analysis purposes, are firstly described. Secondly, this paper discusses and outlines the requirement of a structured and organized computerized platform in order to store, organize and make accessible (for selected and protected usage) dysarthric speech corpora and associated patients' clinical information (mostly disseminated in different locations: labs, hospitals, ...). The design of both a computer database and a multi-field query interface is proposed for the clinical context. Finally, advances of the project related to the selection of the population used for the dysarthria analysis, the preprocessing of the speech files, their orthographic transcription and their automatic alignment are also presented

Multicenter Validation of Histopathologic Tumor Regression Grade After Neoadjuvant Chemotherapy in Muscle-Invasive Bladder Carcinoma

Response classification after neoadjuvant chemotherapy in muscle-invasive bladder carcinoma is based on the TNM stage at radical cystectomy. We recently showed that histopathologic tumor regression grades (TRGs) add prognostic information to TNM. Our aim was to validate the prognostic significance of TRG in muscle-invasive bladder cancer in a multicenter setting. We enrolled 389 patients who underwent cisplatin-based chemotherapy before radical cystectomy in 8 centers between 2010 and 2016. Median follow-up was 2.2 years. TRG was determined in radical cystectomy specimens by local pathologists. Central pathology review was conducted in 20% of cases, which were randomly selected. The major response was defined as ≤pT1N0. The remaining patients were grouped into partial responders (≥ypT2N0-3 and TRG 2) and nonresponders (≥ypT2N0-3 and TRG 3). TRG was successfully determined in all cases, and interobserver agreement in central pathology review was high (κ=0.83). After combining TRG and TNM, 47%, 15%, and 38% of patients were major, partial, and nonresponders, respectively. Combination of TRG and TNM showed significant prognostic discrimination of overall survival (major responder: reference; partial responder: hazard ratio 3.5 [95% confidence interval: 1.8-6.8]; nonresponder: hazard ratio 6.1 [95% confidence interval: 3.6-10.3]). This discrimination was superior compared with TNM staging alone, supported by 2 goodness-of-fit criteria (P=0.041). TRG is a simple, reproducible histopathologic measurement of response to neoadjuvant chemotherapy in muscle-invasive bladder cancer. Integrating TRG with TNM staging resulted in significantly better prognostic stratification than TNM staging alone

Determinants of patient satisfaction in ambulatory oncology: a cross sectional study based on the OUT-PATSAT35 questionnaire

<p>Abstract</p> <p>Background</p> <p>The aim of this study was to identify factors associated with satisfaction with care in cancer patients undergoing ambulatory treatment. We investigated associations between patients' baseline clinical and socio-demographic characteristics, as well as self-reported quality of life, and satisfaction with care.</p> <p>Methods</p> <p>Patients undergoing ambulatory chemotherapy or radiotherapy in 2 centres in France were invited, at the beginning of their treatment, to complete the OUT-PATSAT35, a 35 item and 13 scale questionnaire evaluating perception of doctors, nurses and aspects of care organisation. Additionally, for each patient, socio-demographic variables, clinical characteristics and self-reported quality of life using the EORTC QLQ-C30 questionnaire were recorded.</p> <p>Results</p> <p>Among 692 patients included between January 2005 and December 2006, only 6 were non-responders. By multivariate analysis, poor perceived global health strongly predicted dissatisfaction with care (<it>p </it>< 0.0001). Patients treated by radiotherapy (vs patients treated by chemotherapy) reported lower levels of satisfaction with doctors' technical and interpersonal skills, information provided by caregivers, and waiting times. Patients with primary head and neck cancer (vs other localisations), and those living alone were less satisfied with information provided by doctors, and younger patients (< 55 years) were less satisfied with doctors' availability.</p> <p>Conclusions</p> <p>A number of clinical of socio-demographic factors were significantly associated with different scales of the satisfaction questionnaire. However, the main determinant was the patient's global health status, underlining the importance of measuring and adjusting for self-perceived health status when evaluating satisfaction. Further analyses are currently ongoing to determine the responsiveness of the OUT-PATSAT35 questionnaire to changes over time.</p

CpG-ODN and MPLA Prevent Mortality in a Murine Model of Post-Hemorrhage-Staphyloccocus aureus Pneumonia

Infections are the most frequent cause of complications in trauma patients. Post-traumatic immune suppression (IS) exposes patients to pneumonia (PN). The main pathogen involved in PN is Methicillin Susceptible Staphylococcus aureus (MSSA). Dendritic cells () may be centrally involved in the IS. We assessed the consequences of hemorrhage on pneumonia outcomes and investigated its consequences on DCs functions. A murine model of hemorrhagic shock with a subsequent MSSA pneumonia was used. Hemorrhage decreased the survival rate of infected mice, increased systemic dissemination of sepsis and worsened inflammatory lung lesions. The mRNA expression of Tumor Necrosis Factor-alpha (TNF-α), Interferon-beta (IFN-β) and Interleukin (IL)-12p40 were mitigated for hemorrhaged-mice. The effects of hemorrhage on subsequent PN were apparent on the pDCs phenotype (reduced MHC class II, CD80, and CD86 molecule membrane expression). In addition, hemorrhage dramatically decreased CD8+ cDCs- and CD8- cDCs-induced allogeneic T-cell proliferation during PN compared with mice that did not undergo hemorrhage. In conclusion, hemorrhage increased morbidity and mortality associated with PN; induced severe phenotypic disturbances of the pDCs subset and functional alterations of the cDCs subset. After hemorrhage, a preventive treatment with CpG-ODN or Monophosphoryl Lipid A increased transcriptional activity in DCs (TNF-α, IFN-β and IL-12p40) and decreased mortality of post-hemorrhage MSSA pneumonia

Evidence for Transcript Networks Composed of Chimeric RNAs in Human Cells

The classic organization of a gene structure has followed the Jacob and Monod bacterial gene model proposed more than 50 years ago. Since then, empirical determinations of the complexity of the transcriptomes found in yeast to human has blurred the definition and physical boundaries of genes. Using multiple analysis approaches we have characterized individual gene boundaries mapping on human chromosomes 21 and 22. Analyses of the locations of the 5′ and 3′ transcriptional termini of 492 protein coding genes revealed that for 85% of these genes the boundaries extend beyond the current annotated termini, most often connecting with exons of transcripts from other well annotated genes. The biological and evolutionary importance of these chimeric transcripts is underscored by (1) the non-random interconnections of genes involved, (2) the greater phylogenetic depth of the genes involved in many chimeric interactions, (3) the coordination of the expression of connected genes and (4) the close in vivo and three dimensional proximity of the genomic regions being transcribed and contributing to parts of the chimeric RNAs. The non-random nature of the connection of the genes involved suggest that chimeric transcripts should not be studied in isolation, but together, as an RNA network