DSM (France)

The filamentous fungus Aspergillus niger is widely exploited by the fermentation industry for the production of enzymes and organic acids, particularly citric acid. We sequenced the 33.9-megabase genome of A. niger CBS 513.88, the ancestor of currently used enzyme production strains. A high level of synteny was observed with other aspergilli sequenced. Strong function predictions were made for 6,506 of the 14,165 open reading frames identified. A detailed description of the components of the protein secretion pathway was made and striking differences in the hydrolytic enzyme spectra of aspergilli were observed. A reconstructed metabolic network comprising 1,069 unique reactions illustrates the versatile metabolism of A. niger. Noteworthy is the large number of major facilitator superfamily transporters and fungal zinc binuclear cluster transcription factors, and the presence of putative gene clusters for fumonisin and ochratoxin A synthesis.

BACKGROUND: Ageing is a highly complex process marked by a temporal cascade of events, which promote alterations in the normal functioning of an individual organism. The triggers of normal brain ageing are not well understood, even less so the factors which initiate and steer the neuronal degeneration, which underpin disorders such as dementia. A wealth of data on how nutrients and diets may support cognitive function and preserve brain health are available, yet the molecular mechanisms underlying their biological action in both normal ageing, age-related cognitive decline, and in the development of neurodegenerative disorders have not been clearly elucidated. OBJECTIVES: This review aims to summarise the current state of knowledge of vulnerabilities that predispose towards dysfunctional brain ageing, highlight potential protective mechanisms, and discuss dietary interventions that may be used as therapies. A special focus of this paper is on the impact of nutrition on neuroprotection and the underlying molecular mechanisms, and this focus reflects the discussions held during the 2nd workshop 'Nutrition for the Ageing Brain: Functional Aspects and Mechanisms' in Copenhagen in June 2016. The present review is the most recent in a series produced by the Nutrition and Mental Performance Task Force under the auspice of the International Life Sciences Institute Europe (ILSI Europe). CONCLUSION: Coupling studies of cognitive ageing with studies investigating the effect of nutrition and dietary interventions as strategies targeting specific mechanisms, such as neurogenesis, protein clearance, inflammation, and non-coding and microRNAs is of high value. Future research on the impact of nutrition on cognitive ageing will need to adopt a longitudinal approach and multimodal nutritional interventions will likely need to be imposed in early-life to observe significant impact in older age.

A meta-analysis was conducted (i) to evaluate broiler response to partial or total substitution of corn by sorghum and millet and (ii) to determine the effect of soybean meal replacement by cottonseed meal in broiler diet. The database included 190 treatments from 29 experiments published from 1990 to 2013. Bird responses to an experimental diet were calculated relative to the control (Experimental-Control), and were submitted to mixed-effect models. Results showed that diets containing millet led to similar performance as the corn-based ones for all parameters, whereas sorghum-based diets decreased growth performance. No major effect of the level of substitution was observed with millet or cottonseed meal. No effect of the level of substitution of sorghum on feed intake was found; however, growth performance decreased when the level of substitution of corn by sorghum increased. Cottonseed meal was substituted to soybean meal up to 40% and found to increase feed intake while reducing growth performance. Young birds were not more sensitive to these ingredients than older birds since there was no negative effect of these ingredients on performance in the starter phase. Results obtained for sorghum pointed out the necessity to find technological improvements that will increase the utilization of these feedstuffs in broiler diet. An additional work is scheduled to validate these statistical results in vivo and to evaluate the interactions induced with the simultaneous inclusions of sorghum, millet and cottonseed meal in broiler feeding.

The welfare of ducks can be affected by unwanted behaviors such as excessive reactivity and feather pecking. Providing long-chain n-3 polyunsaturated fatty acids (LC n-3 PUFA) during gestation and early life has been shown to improve the brain development and function of human and rodent offspring. The aim of this study was to test whether the pecking behavior of Muscovy ducks during rearing could be reduced by providing LC n-3 PUFA during embryonic and/or post-hatching development of ducklings. Enrichment of eggs, and consequently embryos, with LC n-3 PUFA was achieved by feeding female ducks (n-3F) a diet containing docosahexaenoic (DHA) and linolenic acids (microalgae and linseed oil). A control group of female ducks (CF) was fed a diet containing linoleic acid (soybean oil). Offspring from both groups were fed starter and grower diets enriched with DHA and linolenic acid or only linoleic acid, resulting in four treatment groups with 48 ducklings in each. Several behavioral tests were performed between 1 and 3 weeks of age to analyze the adaptation ability of ducklings. The growth performance, time budget, social interactions, feather growth, and pecking behavior of ducklings were recorded regularly during the rearing period. No significant interaction between maternal and duckling feeding was found. Ducklings from n-3F ducks had a higher body weight at day 0, 28, and 56, a lower feed conversion ratio during the growth period, and lower reactivity to stress than ducklings from CF ducks. Ducklings from n-3F ducks also exhibited a significantly reduced feather pecking frequency at 49 and 56 days of age and for the whole rearing period. Moreover, consumption of diets enriched with n-3 PUFA during the starter and grower post-hatching periods significantly improved the tibia mineralization of ducklings and the fatty acid composition of thigh muscles at 84 days of age by increasing the n-3 FA content.

Abstract. Heavy precipitation events and subsequent flash floods regularly affect the Mediterranean coastal regions. In these situations, forecasting rainfall and river discharges is crucial especially up to 6 h, which is a relevant lead time for emergency services in times of crisis. The present study investigates the hydrometeorological skills of two new nowcasting systems: a numerical weather model AROME-NWC and a nowcasting system blending numerical weather prediction and extrapolation of radar estimation called PIAF. Their performance is assessed for 10 past heavy precipitation events that occurred in southeastern France. Precipitation forecasts are evaluated at a 15- min time resolution and the availability times of forecasts, based on the operational Météo-France suites, are taken into account when performing the evaluation. Rainfall observations and forecasts were first compared using a point-to-point approach. Then the evaluation was conducted from an hydrological point of view, by comparing observed and forecast precipitation over watersheds affected by floods. In general, the results led to the same conclusions for both evaluations. On the very first lead times, up to 1 h 15 min and 1 h 30 min of forecast, the performance of PIAF was higher than AROME-NWC. For longer lead times (up to 3 h) their performances were generally equivalent. An assessment of river discharges simulated with the ISBA-TOP coupled system, which is dedicated to Mediterranean flash flood simulations and driven by AROME-NWC and PIAF rainfall forecasts, was also performed on two exceptional past flash flood events. The results obtained for these two events show that using AROME-NWC or PIAF rainfall forecasts is promising for flash flood forecasting in terms of peak intensity, timing, and first wave of discharge, with an anticipation of these phenomena that can reach several hours.

Background: The EU ban on antimicrobial growth promoters (AGP) has initiated a search for non-antibiotic alternatives. It has been demonstrated that certain antibiotics and non-antibiotic alternatives enhance growth by inhibiting inflammatory cells, i.e. neutrophils and macrophages in the intestine. There is very little information on the effect of anti-inflammatory compounds on intestinal epithelial cells, which are known to play an important role in intestinal inflammatory responses. In order to establish this, a porcine intestinal epithelial cell line (IPEC J2) was incubated with an adherent enterotoxigenic E. coli (ETEC) to stimulate inflammation, using a non-pathogenic non-adherent E. coli (EC) as a control. The influence of the presence of the anti-inflammatory compounds Macleaya cordata extract (MCE) and acetylsalicylic acid (ASA) on inflammatory transcriptional responses was studied. Results: ETEC induced a strong inflammatory response as was most evident from the expression of IL-1β, IL-8 and TNF-α, whereas EC induced IL-1β only. Co-incubation with MCE and ASA significantly reduced the responses of the pro-inflammatory cytokines, similarly for IL-1β and TNF-α, but ASA was more effective than MCE in reducing the IL8 response. Conclusions: The present results suggest that the in vivo anti-inflammatory growth promoting effects of AGP and effective alternatives to AGP such as MCE and ASA are not restricted to inflammatory cells and also involve the more abundant enterocytes. This suggests a major role for epithelial cells in growth promotion livestock, and it further supports the notion that effective alternatives to AGP should have anti-inflammatory activity.

International audience

Review of: "A nanostructure is any structure with one or more dimensions and it is measured in the range of nanometer scale."

The generation of energetic electrons by the interaction of a short laser pulse with solid “grating” targets, having a periodic groove on the irradiated surface, has been investigated in a regime of ultrahigh contrast (10¹²) and relativistically strong intensity (> 10¹⁹W/cm²). A strong enhancement of both the energy and number of electrons emitted from the target, with respect to at targets, has been observed for incidence angles close to the resonant condition for surface wave excitation. In particular we identified bunches of electrons with energies exceeding 10 MeV which are emitted in a direction close to the target surface. The experimental results are well reproduced by a three-dimensional particle-in-cell simulation, which confirms the dominant role of the surface wave in accelerating the electrons. These results are a step forward the development of high field plasmonics for a number of applications.

Review of: "Some nanowires are ballistic conductors .In normal conductors, electrons collide with atoms in the conductor material."

Since 1984, infrared sensors devices have been developed in the CEA-LETI laboratories for astronomical observation in the 4-17 micrometers wavelength band using Si:Ga detectors. These devices are to equip ISOCAM, a camera which will operate from ISO (Infrared Space Observatory), the European satellite expected to be launched in May 1993, and C10(mu) , a French astronomical camera which will be based at the CFHT (Canadian French Hawaii Telescope). In this paper, a brief description of the devices and their operating conditions, as well as main preliminary results, are given.

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The long-wavelength channel detector of Isocam, a camera aboard the Iso satellite designed to provide 32 x 32 pictures in the 2.5-5.5 micron and 4-17 micron bands, is discussed. The detector, readout circuit, and hybridization technology are addressed, and the main electrooptical measurements are reported. The spatial qualification of the device is briefly addressed.

National audience

Abstract Introduction : Alternative donor Hematopoietic Stem Cell Transplantation (HSCT) is often associated with delayed immune reconstitution compared to matched donors, especially in recipients of CD34+-selected haploidentical transplants. We previously demonstrated in preclinical models that the administration of CD7+ T cell progenitors, produced ex vivo, promotes thymic regeneration and accelerates polyclonal T-cell production. These findings supported the clinical development of human allogenic T lymphoid progenitors (HTLP) to accelerate post-HSCT immune reconstitution in transplanted patients for Severe Combined Immune Deficiencies (SCID). Here, we present the final results of the HTLP-Necker study. Method : We conducted a first-in-human, open-label clinical trial (EudraCT 2019-004883-23) to evaluate the safety and efficacy of HTLP administered after haplo CD34+-selected allogeneic HSCT in patients with SCID. Fresh HTLP were infused between days +7 or after cryopreservation at +14 post-HSCT, following ATG clearance. The Investigational Medicinal Product was manufactured under GMP-conditions from donor CD34+ cells and consisted of CD7+ CD3– lymphoid progenitors. Key outcomes included safety, engraftment, T-cell recovery, thymic activity, and infection rates. Results: Four SCID patients received HTLP following CD34+-selected HSCT. HTLP products showed robust differentiation (median 79.7% CD7+ CD3–) and expansion (median 14.7-fold). Infused doses ranged from 0.1 to 0.3 ×10⁶ CD7+CD3-cells/kg, with minimal residual CD3+ cells (<11.2/kg). After a median follow-up of 63 months (range, 1.5-156 months), no infusion-related toxicity or chromosomal instability was observed. One patient died from severe veno-occlusive disease (VOD) on day 53, unrelated to HTLP. Two out of three patients achieved successful primary engraftment, no grade ≥2 acute Graft Versus Host Disease (GVHD) occurred, and CD3+ CD4+ TCRαβ+ T cells exceeded 50/μL by month four. One patient with residual maternal T-cells experienced a temporary skin flare linked to maternal T-cell alloreactivity, as confirmed by chimerism studies. The progressive acquisition of allogeneic T chimerism is associated with the resolution of maternal-fetal GVH symptoms. We performed short and long-term analysis of intrathymic activity (TREC, RTE quantification, and thymic ultrasound). Both patients experienced effective long-term T cell reconstitution, with 1185 and 1672 T-CD4/mm³, respectively, and 65% of RTE at M24. No viral reactivations or disease relapses were reported. To contextualize these results, we performed a Bayesian comparative analysis of CD4+ T-cell reconstitution against age- and genotype-matched SCID patients receiving standard haploidentical CD34+-selected HSCT. HTLP-treated patients showed earlier and stronger CD4+ recovery. In addition, TCRβ repertoire analysis revealed greater diversity compared to historical controls. Conclusion : HTLP infusion post-HSCT is feasible and safe, with no infusion-related toxicity or severe GVHD. Longitudinal data demonstrate early, robust, and sustained T-cell reconstitution, supported by intrathymic activity. HTLPs may represent a promising strategy to enhance immune recovery in patients undergoing alternative donor transplantation.

A sensor based on selective optical absorption allows monitoring of hazardous engine exhaust emissions such as gaseous hydrocarbons and carbon monoxide. The IR components presented here offer the potential to develop a compact, fast and selective sensor reaching the technical and cost requirements for on-board automotive applications. Optical gas monitoring requires light sources above 3μm since most of the gas species have their fundamental absorption peaks between 3 and 6 μm. We report here on resonant microcavity light sources emitting at room temperature between 3 and 5μm. The emitter combines a Cd_xHg_1-xTe light emitting heterostructure and two dielectric multilayered mirrors. It is optically pumped by a commercial III-V laser diode. The principle of the resonant microcavity emitter allows tailoring of the emission wavelength and the line width to fit the absorption band of a specific gas, ensuring a very good selectivity between species. Moreover, this kind of emitter allows fast modulation enabling high detectivity and short response time. We report performances of light sources in the range 3-5μm allowing the detection of hydrocarbons and carbon monoxide. Association of emitters peaking at different characteristic wavelengths with a single broad band detector allows designing of an optical sensor for several gas species. Sensitivity and time response issues have been characterized: detection of less than 50ppm of CH₄ on a 15cm path has been demonstrated on synthetic gas; analysis of exhaust gases from a vehicle has allowed cylinder to cylinder resolution. This optical sensor offers the potential of various on-board automotive applications.

International audience

Abstract Delayed immune reconstitution following allogeneic hematopoietic cell transplant (allo-HCT) increases the risk of infection, graft failure, and relapse. To address this, immobilized DLL4-Fc (recombinant Delta-like 4 fused to an Fc domain) has been developed to generate human T lymphoid precursors from hematopoietic stem and progenitor cells (HSPCs) in a scalable, GMP-compatible manner. While this platform is under evaluation in early-phase clinical trials, its mechanistic and therapeutic potential has not been systematically tested in preclinical allo-HCT models. To enable preclinical evaluation, we adapted and optimized the DLL4-Fc platform for murine HSPCs. By culturing bone marrow (BM)-derived Lineage-Sca1+cKit+ (“LSK”) cells with IL-7, Flt3L, and SCF on DLL4-Fc coated plates, we consistently achieved >2,000-fold expansion over 2–3 weeks. The resulting population consisted of >95% purity for the DN2 (lineage-CD44+CD25-) and DN3 (lineage-CD44+CD25-) T cell precursors (hereafter “PreT”), providing a robust and scalable source of murine PreTs for downstream in vivo applications. To assess in vivo functionality, we used a well-established MHC-disparate murine allo-HCT model (C57BL/6→BALB/c) with LSK allograft. Adoptively transferred DLL4-generated PreTs successfully engrafted in the thymus and significantly increased total thymic cellularity compared to controls (p<0.05). This effect was dose-dependent, beginning at 2×10⁶ cells (p<0.05) and further enhanced at 4×10⁶ cells (p<0.01), supporting a quantitative benefit of PreT dosing. PreTs progressed through canonical thymocyte stages by day 30 post-transplant, confirming successful intrathymic maturation. Beyond their intrathymic development, PreTs also promoted regeneration of the thymic microenvironment. On day 30 post-transplant, we observed accelerated recovery of thymic stromal compartments, including thymic epithelial cells (TECs, p<0.01) and endothelial cells (ECs, p<0.05), accompanied by increased Ki-67 expression (both p<0.05), indicating enhanced proliferation. Notably, PreT therapy significantly increased de novo thymopoiesis from donor LSK cells, beginning at the early thymic progenitor stage and spanning all maturation stages. By day 30, we observed increased numbers of mature CD4+ and CD8+ single-positive T cells, derived from both PreTs and donor HSPCs (all p<0.05), in the thymus and spleen, indicating successful intrathymic maturation and peripheral emigration. Through their dual impact on both direct thymopoiesis and stromal regeneration, PreTs significantly enhanced overall thymic cellularity on day 30 (p<0.0001). In contrast, TCRb-/- PreTs failed to accelerate TEC or EC recovery, suggesting that the effect on stromal regeneration is dependent on T cell lineage commitment. Transcriptomic analysis using bulk RNA sequencing revealed that cultured PreTs, compared to LSKs, expressed higher levels of thymotropic factors known to support stromal regeneration, including Tnfsf11, Fgf7, Bmp4, Lta. Further mechanistic studies are ongoing to define the Pre-stroma crosstalk that supports thymic regeneration. We next assessed the effects of PreT therapy in allo-HCT recipients with heightened thymic impairment due to aging or post-transplant cyclophosphamide (PTCy). In these clinically relevant settings, PreT treatment significantly increased total thymic cellularity in both 5- and 9-month-old recipients, as well as in mice receiving PTCy (50mg/kg on days +3/+4) (all p<0.05). These findings demonstrate that PreT therapy remains effective despite age-related stromal degeneration and direct exposure to cyclophosphamide, supporting its broader utility in allo-HCT. We evaluated whether PreT therapy enhances peripheral T cell function by infecting allo-HCT recipients with acute lymphocytic choriomeningitis virus (Armstrong strain) on day 30 post-transplant. By day 8 post-infection, PreT-treated mice showed significantly higher frequencies of CD8+ T cells producing TNF-α, IFN-γ, and GzmB, indicating enhanced antiviral responses. We then assessed graft-versus-tumor activity across multiple relapse models (lymphoma, plasmacytoma, leukemia) and found that PreT therapy consistently reduced tumor burden regardless of MHC compatibility. Importantly, no graft-versus-host disease was observed. These findings highlight DLL4-derived PreTs as a GMP-compatible cellular therapy to enhance immune reconstitution and confer antiviral and antitumor activity post-HCT.

A meta-analysis was performed to investigate bird's response on some selected alternative feed ingredients: millet, sorghum and cottonseed meal. The database used contained 186 treatments from 25 different experiments published from 1990 to 2013. A 1-way ANOVA was performed to determine the difference induced by each ingredient on average daily feed intake, body weight gain and feed conversion ratio, compared to control diets. Besides, mixed effects models were developed to test the impact of the level of substitution on all parameters during starter and growing phases. Results indicated an effect of the type of feed ingredient on feed intake and growth performance with better efficiency obtained in millet. No linear relationship was established between level of substitution and variables of interest for all ingredients (R²=0). Additionally, the root mean square error (RMSE) determined for each subset of data demonstrated that observations of this study are practically predictable. Therefore, it is in perspective of this work to predict bird's response to those ingredients nutrients supply. This meta-analytic approach provides significant quantitative knowledge to utilize those ingredients at different levels without any detrimental effect in broilers. Regarding the anti-nutritional factors content of some of these ingredients, it would be interesting to further suggest improvements leading to an increasing utilization of these alternative feedstuffs in poultry.

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