Search

Introduction Our aim was to, firstly, identify characteristics at first-episode of psychosis that are associated with later antipsychotic treatment resistance (TR) and, secondly, to develop a parsimonious prediction model for TR. Methods We combined data from ten prospective, first-episode psychosis cohorts from across Europe and categorised patients as TR or non-treatment resistant (NTR) after a mean follow up of 4.18 years (s.d. = 3.20) for secondary data analysis. We identified a list of potential predictors from clinical and demographic data recorded at first-episode. These potential predictors were entered in two models: a multivariable logistic regression to identify which were independently associated with TR and a penalised logistic regression, which performed variable selection, to produce a parsimonious prediction model. This model was internally validated using a 5-fold, 50-repeat cross-validation optimism-correction. Results Our sample consisted of N = 2216 participants of which 385 (17 %) developed TR. Younger age of psychosis onset and fewer years in education were independently associated with increased odds of developing TR. The prediction model selected 7 out of 17 variables that, when combined, could quantify the risk of being TR better than chance. These included age of onset, years in education, gender, BMI, relationship status, alcohol use, and positive symptoms. The optimism-corrected area under the curve was 0.59 (accuracy = 64 %, sensitivity = 48 %, and specificity = 76 %). Implications Our findings show that treatment resistance can be predicted, at first-episode of psychosis. Pending a model update and external validation, we demonstrate the potential value of prediction models for TR.

8 pages; International audience; Among Plant Protection Products (PPP), a new emerging category of pesticides act by stimulating plant defense in order to improve plant resistance against microbial pathogens. Given that these compounds, the so-called Plant Defense Stimulators (PDS) act on innate immunity, we tested, using an in vitro approach on human mononuclear leucocytes (PBMC), the potential toxicity (XTT assay) and inflammatory effects (production of IL-1β) of 4 PPP belonging to different chemical families. We found that two products (LBG-01F34® and Regalis®) did not induce any cytotoxicity or IL-1 β production. The product BION-50 WG®, that contains Acibenzolar-S-methyl (ASM) and silica particles did not present any cytotoxicity but induced a significant increase in the production of the inflammatory cytokine IL-1 β. Finally, Vacciplant® that contains laminarin, was highly cytotoxic and pro-inflammatory. It induced a strong production of IL-1 β when used at a concentration in the culture medium, as low as 0.02 mg/mL. We also tested the potential toxic effect of these 4 PPP on 4 days old zebra fish larvae. After 24 h of exposure, our results indicate that Vacciplant® induced zebra fish larvae mortality at concentration of 20 μg/mL. LBG did not induced significant mortality at concentrations up to 1 mg/mL whereas Regalis was lethal for 0,3 mg/mL concentrations and BION-50 WG began to induce mortality at 2,5 mg/mL. Our results indicate possible effects of PDS on IL-1β production in human cells and fish survival, calling for more studies on the potential noxious side effects of these compounds.

Two of the most attractive characteristics of Concentrated Solar Power are the high-quality heat exploitable and its capacity for thermal energy storage, which enhance the energy dispatchability in comparison with other renewable sources such as photovoltaics or wind. Consistent efforts are therefore direct to the research of suitable thermodynamic cycles and energy storage systems with low thermal losses and high operating temperatures. However, in the most developed technologies, based on sensible and latent heat storage, high thermal losses are the direct consequence of high operating temperatures. As alternative, Thermochemical Energy Storage systems are gaining attention in the last years.The present work investigates the adoption of a novel Calcium-Looping system for Thermochemical Energy Storage, focusing on the integration on carbonator side. This key integration is directly linked to the energy delivery from the energy storage system and therefore power generation capacity of the plant. An optimization of the carbonator side plant is performed for a direct integration layout, where carbon dioxide from the carbonator evolves through the power block. This analysis aims to maximize the system efficiency acting both on the process components operation and on the thermal transfer between the involved streams. The optimization relies on a novel method based on a genetic algorithm. The pinch analysis is adopted for this study and proper constraints are provided to obtain a configuration exploiting only the renewable energy source. A multi-objective optimization is performed to find out the heat exchanger network topology changes that occur for different operating conditions and derived from this analysis suggestion for systems integration are provided. Keywords: Concentrated Solar Power, Calcium-Looping, HEATSEP, Brayton cycle, Long term energy storage

Tumor cell metabolism is altered during leukemogenesis. Cells performing oxidative phosphorylation (OXPHOS) generate reactive oxygen species (ROS) through mitochondrial activity. To limit the deleterious effects of excess ROS, certain gene promoters contain antioxidant response elements (ARE), e.g. the genes NQO-1 and HO-1. ROS induces conformational changes in KEAP1 and releases NRF2, which activates AREs. We show in vitro and in vivo that OXPHOS induces, both in primary leukemic cells and cell lines, de novo expression of NQO-1 and HO-1 and also the MAPK ERK5 and decreases KEAP1 mRNA. ERK5 activates the transcription factor MEF2, which binds to the promoter of the miR-23a–27a–24-2 cluster. Newly generated miR-23a destabilizes KEAP1 mRNA by binding to its 3′UTR. Lower KEAP1 levels increase the basal expression of the NRF2-dependent genes NQO-1 and HO-1. Hence, leukemic cells performing OXPHOS, independently of de novo ROS production, generate an antioxidant response to protect themselves from ROS., Graphical abstract, Highlights • Leukemic cells performing OXPHOS increase ROS and antioxidant gene expression. • OXPHOS-mediated ERK5 activation induces miR-23 expression through MEF2. • miR-23 blocks KEAP1 expression and increases antioxidant genes. Cells performing oxidative phosphorylation (OXPHOS) generate reactive oxygen species (ROS) through mitochondrial activity. Excess ROS is deleterious to cells; hence they should be kept at bay. We show here that leukemic cells have a genetic program that allow them to generate an antioxidant response when performing OXPHOS and this is independent of ROS generation. Because leukemic cells need protection from ROS, this pathway is a potential target for therapeutic intervention.

International audience; A process has been validated for the deconstruction of lignocellulose on a pilot scale installation using six types of biomass selected for their sustainability, accessibility, worldwide availability, and differences of chemical composition and physical structure. The process combines thermo-mechano-chemical and bio-catalytic action in a single twin-screw extruder. Three treatment phases were sequentially performed: an alkaline pretreatment, a neutralization step coupled with an extraction–separation phase and a bioextrusion treatment. Alkaline pretreatment destructured the wall polymers after just a few minutes and allowed the initial extraction of 18–54% of the hemicelluloses and 9–41% of the lignin. The bioextrusion step induced the start of enzymatic hydrolysis and increased the proportion of soluble organic matter. Extension of saccharification for 24 h at high consistency (20%) and without the addition of new enzyme resulted in the production of 39–84% of the potential glucose.

Cinnamyl alcohol dehydrogenase (CAD) is a key enzyme involved in the last step of monolignol biosynthesis. The effect of CAD down-regulation on lignin production was investigated through a transgenic approach in maize. Transgenic CAD-RNAi plants show a different degree of enzymatic reduction depending on the analyzed tissue and show alterations in cell wall composition. Cell walls of CAD-RNAi stems contain a lignin polymer with a slight reduction in the S-to-G ratio without affecting the total lignin content. In addition, these cell walls accumulate higher levels of cellulose and arabinoxylans. In contrast, cell walls of CAD-RNAi midribs present a reduction in the total lignin content and of cell wall polysaccharides. In vitro degradability assays showed that, although to a different extent, the changes induced by the repression of CAD activity produced midribs and stems more degradable than wild-type plants. CAD-RNAi plants grown in the field presented a wild-type phenotype and produced higher amounts of dry biomass. Cellulosic bioethanol assays revealed that CAD-RNAi biomass produced higher levels of ethanol compared to wild-type, making CAD a good target to improve both the nutritional and energetic values of maize lignocellulosic biomass., This work was supported by the Spanish ‘Ministerio de Ciencia e Innovación’ (AGL2008–05157), the European Community (‘COPOL’ project: integrated control of polysaccharide and lignin biosynthesis to improve cellulose content and availability and fibre quality, QLK5-CT-2000–01493), and the CONSOLIDER-INGENIO program (CSD2007–00036). S.F. was financed by an I3P contract from the ‘Consejo Superior de Investigaciones Científicas’. D.C.-R. was initially financed by the Spanish ‘Ministerio de Educación y Ciencia’ (‘Ramón y Cajal’ Program). A.E. was financed by DGICYT (CGL2008–02470BOS) and Junta de Castilla y León (LE004A10-2). This work was carried out within the framework of the ‘Xarxa de Referència de Biotecnologia’ (XarBa) from the Autonomous Government of Catalonia.

International audience; To select a Saccharomyces cerevisiae reference strain amenable to experimental techniques used in (molecular) genetic, physiological and biochemical engineering research, a variety of properties were studied in four diploid, prototrophic laboratory strains. The following parameters were investigated: 1) maximum specific growth rate in shake-flask cultures; 2) biomass yields on glucose during growth on defined media in batch cultures and steady-state chemostat cultures under controlled conditions with respect to pH and dissolved oxygen concentration; 3) the critical specific growth rate above which aerobic fermentation becomes apparent in glucose-limited accelerostat cultures; 4) sporulation and mating efficiency; and 5) transformation efficiency via the lithium-acetate, bicine, and electroporation methods. On the basis of physiological as well as genetic properties, strains from the CEN.PK family were selected as a platform for cell-factory research on the stoichiometry and kinetics of growth and product formation.