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ScopeEpidemiological and experimental evidence reported that processed meat consumption is associated with colorectal cancer (CRC) risk. Several studies suggest the involvement of nitrite or nitrate additivesvia N-nitroso-compound formation (NOCs).Methods and resultsCompared to the reference level (120 mg/kg of ham), the effects of sodium nitrite reduction (90 mg/kg of ham), removal and replacement were analysed on ham characteristics and in a CRC rat model. Sodium nitrite removal and reduction induced a similar decrease in CRC preneoplastic lesions, but only reduction led to (i) an inhibitory effect onListeria monocytogenesgrowth comparable to that obtained using the reference nitrite level of 120 mg/kg and (ii) an effective control of lipid peroxidation. Among the three alternatives tested, none led to a significant gain when compared to the 120 mg/kg ham reference level: vegetable stock, due to nitrate presence, was very similar to this reference nitrite level, yeast extract induced a strong luminal peroxidation and no decrease in preneoplastic lesions despite the absence of NOCs, and polyphenol rich extract induced the clearest downward trend on preneoplastic lesions but the concomitant presence of nitrosyl iron in feces. Except vegetable stock, other alternatives were less efficient than sodium nitrite (≥ 90 mg/kg) in reducingL. monocytogenesgrowth.ConclusionNitrite reduction (90mg/kg) effectively reduced CRC risk through limiting NOC formation and lipid peroxidation, while mitigatingL. monocytogenesrisks from cooked hams. Going further in reduction should be possible if accompanied by antioxidants to limit lipid peroxidation and appropriate use-by dates.

In addition to its role as a neuronal energy substrate and signaling molecule involved in synaptic plasticity and memory consolidation, recent evidence shows that lactate produces antidepressant effects in animal models. However, the mechanisms underpinning lactate’s antidepressant actions remain largely unknown. In this study, we report that lactate reverses the effects of corticosterone on depressive-like behavior, as well as on the inhibition of both the survival and proliferation of new neurons in the adult hippocampus. Furthermore, the inhibition of adult hippocampal neurogenesis prevents the antidepressant-like effects of lactate. Pyruvate, the oxidized form of lactate, did not mimic the effects of lactate on adult hippocampal neurogenesis and depression-like behavior. Finally, our data suggest that conversion of lactate to pyruvate with the concomitant production of NADH is necessary for the neurogenic and antidepressant effects of lactate.

We investigated the combined effects of biopreservation and high-pressure treatment on bacterial communities of diced cooked ham prepared with diminished nitrite salt. First, bacterial communities of four commercial brands of diced cooked ham from local supermarkets were characterized and stored frozen. Second, sterile diced cooked ham, prepared with reduced levels of nitrite, was inoculated with two different microbiota collected from the aforementioned commercial samples together with a nisin-producing

The mammalian circadian timing system and metabolism are highly interconnected, and disruption of this coupling is associated with negative health outcomes. Krüppel-like factors (KLFs) are transcription factors that govern metabolic homeostasis in various organs. Many KLFs show a circadian expression in the liver. Here, we show that the loss of the clock-controlled KLF10 in hepatocytes results in extensive reprogramming of the mouse liver circadian transcriptome, which in turn, alters the temporal coordination of pathways associated with energy metabolism. We also show that glucose and fructose induce Klf10, which helps mitigate glucose intolerance and hepatic steatosis in mice challenged with a sugar beverage. Functional genomics further reveal that KLF10 target genes are primarily involved in central carbon metabolism. Together, these findings show that in the liver, KLF10 integrates circadian timing and sugar metabolism related signaling, and serves as a transcriptional brake that protects against the deleterious effects of increased sugar consumption.

In recent years, multi-petawatt laser installations have achieved unprecedented peak powers, opening new horizons to laser–matter interaction studies. Ultra-broadband and extreme temporal contrast pulse requirements make optical parametric chirped pulse amplification (OPCPA) in the few-picosecond regime the key technology in these systems. To guarantee high fidelity output, however, OPCPA requires excellent synchronization between pump and signal pulses. Here, we propose a new highly versatile architecture for the generation of optically synchronized pump–signal pairs based on the Kerr shutter effect. We obtained > 550 µ J pump pulses of 12 ps duration at 532 nm optically synchronized with a typical ultrashort CPA source at 800 nm. As a proof-of-principle demonstration, our system was also used for amplification of ∼ 20 µ J ultra-broadband pulses based on an OPCPA setup.

We demonstrate the impact of the optics roughness in Öffner stretchers used in chirped pulse amplification laser chains and how it is possible to improve the temporal contrast ratio in the temporal range of 10–100 ps by adequately choosing the optical quality of the key components. Experimental demonstration has been realized in the front-end source of the multi-petawatt (PW) laser facility Apollon, resulting in an enhancement of the contrast ratio by two to three orders of magnitude.

International audience; Obesity is a growing societal scourge. Recent studies have uncovered that paternal excessive weight induced by an unbalanced diet affects the metabolic health of offspring. These reports mainly employed single-generation male exposure. However, the consequences of multigenerational unbalanced diet feeding on the metabolic health of progeny remain largely unknown. Here, we show that maintaining paternal Western diet feeding for five consecutive generations in mice induces an enhancement in fat mass and related metabolic diseases over generations. Strikingly, chow-diet-fed progenies from these multigenerational Western-diet-fed males develop a ‘healthy’ overweight phenotype characterized by normal glucose metabolism and without fatty liver that persists for four subsequent generations. Mechanistically, sperm RNA microinjection experiments into zygotes suggest that sperm RNAs are sufficient for establishment but not for long-term maintenance of epigenetic inheritance of metabolic pathologies. Progressive and permanent metabolic deregulation induced by successive paternal Western-diet-fed generations may contribute to the worldwide epidemic of metabolic diseases.

We investigated the combined effects of biopreservation and high pressure treatment on bacterial communities of diced cooked ham prepared with diminished nitrite salt. First, bacterial communities of four commercial brands of dice cooked ham from local supermarkets, were characterised and stored frozen. Second, sterile diced cooked ham, prepared with reduced level of nitrite was inoculated with two different microbiota collected from the aforementioned commercial samples together with a nisin producing Lactococcus lactis protective strain able to recover from a 500 MPa high pressure treatment. Dices were then treated at 500 MPa for 5 minutes and bacterial dynamics was monitored during storage at 8°C. Depending on samples, ham microbiota were dominated by different Proteobacteria (Pseudomonas, Serratia, Psychrobacter, or Vibrio) or by Firmicutes (Latilactobacillus and Leuconostoc). Applied alone, none of the treatments stabilized durably the growth of hams microbiota. Nevertheless, the combination of biopreservation and high pressure treatment was efficient to reduce the growth of Proteobacteria spoilage species. However, this effect was dependent on the nature of the initial microbiota, showing that use of biopreservation and high pressure treatment as an alternative to nitrite reduction for ensuring cooked ham microbial safety merits attention but still requires improvement.

International audience; High Pressure Processing (HPP) and biopreservation can contribute to food safety by inactivation of bacterial contaminants. However these treatments are inefficient against bacterial endospores. Moreover, HPP can induce spore germination. The objective of this study was to select lactic acid bacteria strains to be used as bioprotective cultures, to control vegetative cells of spore-forming bacteria in ham after application of HPP. A collection of 63 strains of various origins was screened for their antagonistic activity against spore-forming Bacillus and Clostridium species and their ability to resist to HPP. Some safety requirements should also be considered prior to their introduction into the food chain. Hence, the selection steps included the assessment of biogenic amine production and antibiotic resistance. No strain produced histamine above the threshold detection level of 50 ppm. From the assessment of antibiotic resistance against nine antibiotics, 14 susceptible strains were kept. Antagonistic action of the 14 strains was then assessed by the well diffusion method against pathogenic or spoilage spore-forming species as Bacillus cereus, Clostridium sp. like botulinum, Clostridium frigidicarnis, and Clostridium algidicarnis. One Lactobacillus curvatus strain and one Lactococcus lactis strain were ultimately selected for their widest inhibitory spectrum and their potential production of bacteriocin. A Lactobacillus plantarum strain was included as control. Their resistance to HPP and ability to regrow during chilled storage was then assessed in model ham liquid medium. Treatments of pressure intensities of 400, 500, and 600 MPa, and durations of 1, 3, 6, and 10 min were applied. After treatment, cultures were incubated at 8 °C during 30 days. Inactivation curves were then fitted by using a reparameterized Weibull model whereas growth curves were modelled with a logistic model. Although the two Lactobacillus strains were more resistant than L. lactis to HPP, the latter was the only strain able to regrow following HPP. The absence of biogenic amine production of this strain after growth on diced cube cooked ham was also shown. In conclusion this L. lactis strain could be selected as representing the best candidate for a promising preservative treatment combining biopreservation and HPP to control spore-forming bacteria in cooked ham.

Peroxisome proliferator-activated receptors (PPARs) are nuclear receptors, which function as transcription factors. Among them, PPARβ/δ is highly expressed in endothelial cells. Pharmacological activation with PPARβ/δ agonists had been shown to increase their angiogenic properties. PPARβ/δ has been suggested to be involved in the regulation of the angiogenic switch in tumor progression. However, until now, it is not clear to what extent the expression of PPARβ/δ in tumor endothelium influences tumor progression and metastasis formation. We addressed this question using transgenic mice with an inducible conditional vascular-specific overexpression of PPARβ/δ. Following specific over-expression of PPARβ/δ in endothelial cells, we induced syngenic tumors. We observed an enhanced tumor growth, a higher vessel density, and enhanced metastasis formation in the tumors of animals with vessel-specific overexpression of PPARβ/δ. In order to identify molecular downstream targets of PPARβ/δ in the tumor endothelium, we sorted endothelial cells from the tumors and performed RNA sequencing. We identified platelet-derived growth factor receptor beta (Pdgfrb), platelet-derived growth factor subunit B (Pdgfb), and the tyrosinkinase KIT (c-Kit) as new PPARβ/δ -dependent molecules. We show here that PPARβ/δ activation, regardless of its action on different cancer cell types, leads to a higher tumor vascularization which favors tumor growth and metastasis formation.

Currently, there is major consumer concern about dietary salt intake worldwide. However, even with the development of contemporary preservation practices, sodium chloride is still essential in processed meat products. Despite a long history of use, salt is now seriously controversial in food due to health concerns that are mostly related to high blood pressure and cardiovascular risks. Changes in meat processing methods have reduced those potential risks, but different perceptions continue to shape how consumers and society view dietary salt. The current consumer demand for additive-free food, such as the clean-label movement, has renewed consumer willingness for naturalness in food products.

In the context of organ shortage for transplantation, new criteria for better organ evaluation should be investigated. Ex-vivo lung perfusion (EVLP) allows extra-corporal lung re-conditioning and evaluation, under controlled parameters of the organ reperfusion and mechanical ventilation. This work reports on the interest of exhaled gas analysis during the EVLP procedure. After a 1 h cold ischemia, the endogenous gas production by an isolated lung of nitric oxide and carbon monoxide is simultaneously monitored in real time. The exhaled gas is analysed with two very sensitive and selective laser spectrometers developed upon the technique of optical-feedback cavity-enhanced absorption spectroscopy. Exhaled gas concentration measured for an ex-vivo lung is compared to the corresponding production by the whole living pig, measured before euthanasia. On-line measurements of the fraction of nitric oxide in exhaled gas (FENO) in isolated lungs are reported here for the first time, allowing to resolve the respiratory cycles. In this study, performed on 9 animals, FENO by isolated lungs range from 3.3 to 10.6 ppb with a median value of 4.4 ppb. Pairing ex-vivo lung and pig measurements allows to demonstrate a systematic increase of FENO in the ex-vivo lung as compared to the living animal, by a factor of 3 ± 1.2. Measurements of the fraction of carbon monoxide in exhaled gas (FECO) confirm levels recorded during previous studies driven to evaluate FECO as a potential marker of ischemia reperfusion injuries. FECO production by ex-vivo lungs ranges from 0.31 to 2.3 ppm with a median value of 0.8 ppm. As expected, these FECO values are lower than the production by the corresponding whole pig body, by a factor of 6.9 ± 2.7.

In the aim of reaching high-peak-powers, which may induce deleterious thermal loads, we investigate the spatiotemporal thermal distortions in a PW-laser facility studying the thermal effects (up to 130W/cm²) occurring in a large compressor-gratings.

International audience

The purpose of this study is to prepare a new activated carbon from olive stones for use in gold recovery by carbon-in-leach (CIL) and carbon-in-pulp (CIP). The preparation method chosen was physical activation using steam. The effect of four process parameters: the residence time for carbonization, the activation temperature, the residence time for activation, and steam flow, were studied by the mean of response surface method (RSM) in order to optimize the yield, iodine index, and attrition characteristics. These two last responses were used as primary indicators of gold recovery capacity and mechanical strength. The results obtained show that optimal activated carbon can be prepared under the following conditions: a carbonization time of 157 minutes, activation at 921°C for 53 minutes, and a water vapour flow of 0.18 mL/min. This optimum carbon has an iodine value greater than 1100 mg/g and an attrition index in the order of 0.74%. These values reflect the quality of the precursor (olive stones) as a raw material for the development of an effective new activated carbon for the gold mining industry.

The specifications performance data for the latest generation system are compared to prior generations. These results are shown for both missing pattern (or hard) and unknown contamination (or soft) defects of various classifications in different patterns. For hard defects, capability will be demonstrated down to the 65 nm node, with soft defect repair and clean significantly exceeding to even smaller nodes down to 14 nm. The latter is of particular note, especially in the application of the cleaning of fall-on unknown contaminates on pelliclized photomasks. Finally, there will be a discussion of future work to further develop soft repair/clean process and laser processes for other mask technologies.

According to the Swiss Health Survey one in five people will suffer from a major depressive episode at least once during their lifetime. Antidepressants and psychotherapy play a prominent role in patient management. In recent years, many studies have shown that physical activity also reduces depressive symptoms. Among mechanisms involved in the antidepressant effects of exercise, a recent study based on animal models of depression suggests that lactate may contribute to reducing depressive symptoms in response to physical activity. Elucidation of the mechanisms underlying the antidepressant effects of lactate may contribute to identify novel therapeutic targets for the treatment of depression.L’Enquête suisse sur la santé estime qu’une personne sur cinq souffrira au moins une fois dans sa vie d’un épisode dépressif. Les antidépresseurs, ainsi que la psychothérapie, occupent une place de choix dans la prise en charge des patients. Au cours de ces dernières années, de nombreuses études ont démontré que l’activité physique réduit également les symptômes dépressifs. Parmi les mécanismes impliqués dans les effets antidépresseurs de l’exercice, une étude récente réalisée sur des modèles animaux de dépression suggère que le lactate pourrait contribuer à la réduction des symptômes dépressifs par l’activité physique. L’élucidation des mécanismes qui sous-tendent les effets antidépresseurs de l’activité physique pourrait contribuer à identifier de nouvelles cibles thérapeutiques pour le traitement de la dépression.

International audience; The aim of this paper is to show the advantages of implementing a Quality Management System (QMS) in a research laboratory in order to improve the management of risks specific to research programmes and to increase the reliability of results. This paper also presents experience gained from feedback following the implementation of the Quality process in a research laboratory at INRA, the French National Institute for Agronomic Research and details the various challenges encountered and solutions proposed to help achieve smoother adoption of a QMS process. The 7Ms (Management, Measurement, Manpower, Methods, Materials, Machinery, Mother-nature) methodology based on the Ishikawa ‘Fishbone’ diagram is used to show the effectiveness of the actions considered by a QMS, which involve both the organization and the activities of the laboratory. Practical examples illustrate the benefits and improvements observed in the laboratory

International audience; Choroid plexus carcinomas (CPCs) are highly malignant brain tumours predominantly found in children and associated to poor prognosis. Improved therapy for these cancers would benefit from the generation of animal models. Here we have created a novel mouse CPC model by expressing a stabilised form of c-Myc (MycT58A) and inactivating Trp53 in the choroid plexus of newborn mice. This induced aberrant proliferation of choroid plexus epithelial cells, leading to aggressive tumour development and death within 150 days. Choroid plexus tumours occurred with a complete penetrance in all brain ventricles, with prevalence in the lateral and fourth ventricles. Histological and cellular analysis indicated that these tumours were CPCs resembling their human counterparts. Comparison of gene expression profiles of CPCs and non-neoplastic tissues revealed profound alterations in cell cycle regulation and DNA damage responses, suggesting that dysregulation of cell division and DNA checkpoint pathways may represent key vulnerabilities. This novel animal model of CPC provides an invaluable tool to elucidate the mechanism of CPC formation and to develop successful therapies against this devastating paediatric cancer.

LETI/LIR has been involved for a few year in the field of uncooled detectors and has chosen amorphous silicon for its microbolometer technology development. Uncooled IR detectors pave the way to reduced weight systems aboard satellites. The silicon compatibility of our thermometer is a key parameter which has enabled a very fast technology development and transfer to industry. This competitive technology is now able to provide a new approach for IR detectors for space applications. This paper presents the main characteristics of the CEA / LETI technology which is based on a monolithically integrated structure over a fully completed readout circuit from a commercially available 0.5 μm design rules CMOS line. The technology maturity will be illustrated by the results obtained at LETI/LIR and SOFRADIR on a 320 x 240 with a pitch of 45 μm. First improvement on device reliability and characterization results will be presented.

The neuron-specific K-Cl cotransporter, KCC2, is highly expressed in the vicinity of excitatory synapses in pyramidal neurons, and recent in vitro data suggest that this protein plays a role in the development of dendritic spines. The in vivo relevance of these observations is, however, unknown. Using in utero electroporation combined with post hoc iontophoretic injection of Lucifer Yellow, we show that premature expression of KCC2 induces a highly significant and permanent increase in dendritic spine density of layer 2/3 pyramidal neurons in the somatosensory cortex. Whole-cell recordings revealed that this increased spine density is correlated with an enhanced spontaneous excitatory activity in KCC2-transfected neurons. Precocious expression of the N-terminal deleted form of KCC2, which lacks the chloride transporter function, also increased spine density. In contrast, no effect on spine density was observed following in utero electroporation of a point mutant of KCC2 (KCC2-C568A) where both the cotransporter function and the interaction with the cytoskeleton are disrupted. Transfection of the C-terminal domain of KCC2, a region involved in the interaction with the dendritic cytoskeleton, also increased spine density. Collectively, these results demonstrate a role for KCC2 in excitatory synaptogenesis in vivo through a mechanism that is independent of its ion transport function.

The number of curvilinear patterns present on the masks will increase drastically in the next generations of semiconductor devices. Multibeam mask writers are foreseen to enable a more widespread use of curvilinear shapes. Several applications can benefit from curvilinear patterns like silicon photonics or Inverse Lithography Technology (ILT). We propose a set of innovative algorithms that uses a dedicated representation for curvilinear patterns. This approach simplifies the data handling and decreases file size by reducing the degree of freedom on the database. It also allows improving the output quality with a more precise control of the geometric correction. We illustrate the benefit of using the curvilinear data representation to the Mask Proximity correction and Mask Rule Check.

Study Objectives: There is growing evidence indicating that in order to meet the neuronal energy demands, astrocytes provide lactate as an energy substrate for neurons through a mechanism called "astrocyte-neuron lactate shuttle" (ANLS). Since neuronal activity changes dramatically during vigilance states, we hypothesized that the ANLS may be regulated during the sleep-wake cycle. To test this hypothesis we investigated the expression of genes associated with the ANLS specifically in astrocytes following sleep deprivation. Astrocytes were purified by fluorescence-activated cell sorting from transgenic mice expressing the green fluorescent protein (GFP) under the control of the human astrocytic GFAP-promoter. Design: 6-hour instrumental sleep deprivation (TSD). Setting: Animal sleep research laboratory. Participants: Young (P23-P27) FVB/N-Tg (GFAP-GFP) 14Mes/J (Tg) mice of both sexes and 7-8 week male Tg and FVB/Nj mice. Interventions: Basal sleep recordings and sleep deprivation achieved using a modified cage where animals were gently forced to move. Measurements and Results: Since Tg and FVB/Nj mice displayed a similar sleep-wake pattern, we performed a TSD in young Tg mice. Total RNA was extracted from the GFP-positive and GFP-negative cells sorted from cerebral cortex. Quantitative RT-PCR analysis showed that levels of Glut1, alpha-2-Na/K pump, Glt1, and Ldha mRNAs were significantly increased following TSD in GFP-positive cells. In GFP-negative cells, a tendency to increase, although not significant, was observed for Ldha, Mct2, and alpha-3-Na/K pump mRNAs. Conclusions: This study shows that TSD induces the expression of genes associated with ANLS specifically in astrocytes, underlying the important role of astrocytes in the maintenance of the neuro-metabolic coupling across the sleep-wake cycle.

Depuis 2006, le laboratoire de préservation des bois du Cirad est accrédité par le COFRAC (Comité français d'accréditation - accréditation n°1-1686) pour ses essais sur la durabilité des bois et produits dérivés du bois et sur l'efficacité protectrice des produits de préservation et des produits anti-termites. La mise en place de la fonction métrologie au laboratoire de préservation du bois est un facteur clé de l'amélioration continue des pratiques. De tous les essais de caractérisation des bois, les essais de résistance aux agents biologiques de détérioration sont les plus délicats. Ils visent en effet à évaluer et à quantifier l'impact d'organismes vivants, comme les champignons et les termites, sur une matière lignocellulosique. On apprécie facilement l'importance de la variabilité de cet impact lié lui-même à la diversité de ces organismes. La validité et la fiabilité des résultats dépendront ainsi directement de la qualité du processus métrologique mis en oeuvre, comprenant le choix des appareils de mesure, leur gestion et leur mise en conformité avec les normes internationales. Mots clés: Métrologie, accréditation, traçabilité, incertitude, essais biologiques.

Dislocation densities have been measured in Ni3Al(Hf) single crystals after deformation at various temperatures and strains. In addition, effective and athermal stresses have been determined by strain dip tests. A model is proposed for the strength anomaly domain which correlates the athermal part of the stress with the operation of dislocation sources, to compensate for the strong dislocation exhaustion. Dislocation density data, which evidence an anomaly in the density with temperature over the stress anomaly domain, are shown to support this model predictions between 373 K and 683 K for plastic strains larger than 3 × 10−2 but not at yield. In addition, the presence of Hf atoms (3.3 at. %) induces a friction stress close to 63 MPa.

International audience

International audience

The purpose of the present study was to examine the relationship of harmonious and obsessive passion to perceptions of task and social cohesion in team sport athletes. Participants were 370 competitive (N=252) and recreational (N=118) athletes ranging from 18- to 28-years-old (Mage=20.20, SD=1.52) from a wide variety of team sports. Participants completed the Passion Scale (Vallerand et al., 2003) and the Group Environment Questionnaire (Carron et al., 1985). A MANOVA revealed that competitive athletes were more passionate and had higher perceptions of cohesion than did recreational athletes. Multiple regression analyses revealed a positive relationship between both harmonious and obsessive passion and both task (ATG-T, GI-T) and social (ATG-S, GI-S) cohesion. Theoretical and practical implications are discussed pertaining to the importance of harmonious and obsessive passion in athletes and perceptions of cohesion in competitive and recreational sport.