Receptor Complementation and Mutagenesis Reveal SR-BI as an Essential HCV Entry Factor and Functionally Imply Its Intra- and Extra-Cellular Domains

HCV entry into cells is a multi-step and slow process. It is believed that the initial capture of HCV particles by glycosaminoglycans and/or lipoprotein receptors is followed by coordinated interactions with the scavenger receptor class B type I (SR-BI), a major receptor of high-density lipoprotein (HDL), the CD81 tetraspanin, and the tight junction protein Claudin-1, ultimately leading to uptake and cellular penetration of HCV via low-pH endosomes. Several reports have indicated that HDL promotes HCV entry through interaction with SR-BI. This pathway remains largely elusive, although it was shown that HDL neither associates with HCV particles nor modulates HCV binding to SR-BI. In contrast to CD81 and Claudin-1, the importance of SR-BI has only been addressed indirectly because of lack of cells in which functional complementation assays with mutant receptors could be performed. Here we identified for the first time two cell types that supported HCVpp and HCVcc entry upon ectopic SR-BI expression. Remarkably, the undetectable expression of SR-BI in rat hepatoma cells allowed unambiguous investigation of human SR-BI functions during HCV entry. By expressing different SR-BI mutants in either cell line, our results revealed features of SR-BI intracellular domains that influence HCV infectivity without affecting receptor binding and stimulation of HCV entry induced by HDL/SR-BI interaction. Conversely, we identified positions of SR-BI ectodomain that, by altering HCV binding, inhibit entry. Finally, we characterized alternative ectodomain determinants that, by reducing SR-BI cholesterol uptake and efflux functions, abolish HDL-mediated infection-enhancement. Altogether, we demonstrate that SR-BI is an essential HCV entry factor. Moreover, our results highlight specific SR-BI determinants required during HCV entry and physiological lipid transfer functions hijacked by HCV to favor infection

Evaluation of a policy of restrictive episiotomy on the incidence of perineal tears among women with spontaneous vaginal delivery: A ten-year retrospective study

International audienceIntroduction: Routine episiotomy is no longer recommended to limit obstetrical anal sphincter injuries (OASIs). We aimed to evaluate the effect of a restrictive policy of episiotomy on the risk of OASIs during spontaneous vaginal deliveries.Material and methods: We performed a retrospective single-center observational study among women with a term singleton cephalic fetus, with spontaneous vaginal delivery. The occurrence of episiotomy, intact perineum, first, second, third or fourth-degree (OASIs) perineal tears were compared before (period A, from 01/01/2006 to 12/31/2008) and after (period B, from 01/01/2012 to 12/31/2016) implementation of the restrictive policy. Odds of perineal tear were estimated using multivariable logistic regression models, stratified by parity.Results: From 2006-2016, the rate of episiotomy decreased, from 14.9 % (n/N = 200/1141) to 4.7 % (94/1912). In period B (N = 8984) vs A (N = 8984), the rates of episiotomy were, 12.9 vs 26.6 % for nulliparas (p < 0.01) and 2.3 vs 6.8 % for multiparas (p < 0.01). Odds of OASIs were not different in period B vs A, both for nulliparas (0.9 vs 0.8 %, AOR = 0.88(0.38-2.05)) and multiparas (0.4 vs 0.2 %, AOR = 2.28(0.63-8.29). Odds of second-degree tear were higher in period B vs A, both for nulliparas (39.8 vs 17.4 %, AOR = 2.55 (2.11-3.08) and multiparas (26.2 vs 12.8 %, AOR = 2.26(1.95-2.66)); and odds of intact perineum were lower (for nulliparas, 15.8 vs 24.9 %, AOR = 0.61(0.42-0.90) and for multiparas, 47.1 vs 56.0 %, AOR = 0.61 (0.49-0.76)). No difference was observed for first-degree tears.Conclusion: The progressive implementation of a restrictive policy of episiotomy during spontaneous vaginal delivery was not associated with an increased risk of OASIs over a ten-year period. (C) 2020 Elsevier Masson SAS. All rights reserved

Impact of Destroying the Structure of Model Gels on Volatile Release

International audienceThe release of a strawberry aroma from different composite gels taken as models of fruit preparations and from a sucrose solution was investigated. The composition of the model systems differed with regard to the gelling agent, either pectin or carrageenan, and to the rigidity of the gel. With the use of atmospheric pressure chemical ionization−mass spectrometry, the release profiles of the aroma compounds were determined under stirring. At the same time, purge and trap measurements were performed to determine the release profiles of the aroma compounds without stirring. The comparison of the patterns obtained using these two complementary methods made it possible to determine how the structure of the matrix, the mechanical treatment, and the properties of the aroma compound affect aroma release. A far greater proportion of the aroma compounds was retained in the fruit preparation systems than in the sucrose solution. The different release profiles could be interpreted in terms of the volatility of the aroma compounds and of their diffusion through the gels

Évaluation quantitative et qualitative des infections sur cathéter veineux central chez les nouveau-nés de moins de 1500 grammes à la naissance dans les services de réanimation et de médecine néonatales

Résumé Objectifs : Déterminer le taux d’incidence des bactériémies liées aux cathéters veineux centraux chez les nouveau-nés de moins de 1500 grammes à la naissance, et tenter d’identifier les facteurs de risques. Méthodologie : Une étude rétrospective monocentrique a été réalisée entre le 1er janvier 2009 et le 31 janvier 2010, incluant les nouveau-nés de moins de 1500 grammes à la naissance hospitalisés dans les premières 48 heures de vie dans les services de réanimation et de médecine néonatales. Pour rechercher les facteurs de risques, les tests de Student et du Khi-2, puis une régression logistique ont été utilisés. Résultats : Cent onze nouveau-nés ont été inclus et 26 bactériémies liées aux cathéters veineux centraux diagnostiquées soit une incidence de 11,98 pour 100 cathéters veineux centraux et un taux d’incidence de 10,22 % jours-cathéter veineux central. Si l’on distingue les cathéters veineux ombilicaux des autres cathéters veineux centraux, le taux d’incidence est de 3,33 % jours-cathéter veineux ombilical et de 11,15 % jours-cathéter veineux épicutanéocave. Le faible âge gestationnel apparaît comme facteur de risque de bactériémies liées aux cathéters veineux centraux. Dans la population nécessitant la pose de cathéters veineux centraux épicutanéocaves, les facteurs de risques indépendants sont la faiblesse de l’âge gestationnel et de la durée de la présence du cathéter veineux épicutanéocave. Conclusion : Dans l’échantillon étudié, le taux d’incidence des bactériémies liées aux cathéters veineux centraux est comparable à celle trouvée dans le réseau NEOCAT 2009 observant plusieurs services de réanimation et de médecine néonatales français. Abstract Objectives: To determine the rate of occurrence of bacteremias related to central venous access catheters in newborns weighing less than 1500 grams at birth. To identify risk factors. Methods: A retrospective, single-centre study was conducted January 1, 2009–January 31, 2010. Included were newborns of less than 1500 grams at birth that were hospitalized in the first 48 hours of life under neonatal medicine and resuscitation services. To evaluate risk factors, Student T and Chi-squared tests were used, followed by logistic regression. Results: One hundred and eleven newborns and 26 bacteremias related to central venous catheters were included, revealing an incidence of 11.98 per 100 central venous catheters and an incidence of 10.22‰ central venous catheter-days. If a distinction is made between umbilical venous catheters and other central venous catheters, the incidence is 3.33‰ umbilical venous catheter-days and 11.15‰ epicutaneo-cava venous catheter days. Early gestational age appears as a risk factor for bacteremias related to central venous catheters (p = 0.03 significant). In the population requiring epicutaneo-cava venous catheters, independent risk factors are low gestational age, and the duration of epicutaneo-cava central venous catheters (respectively p=0.001 and 0.002 significant). Conclusion: In the study sample, the incidence of bacteremias related to central venous catheters is comparable to the incidence found on the NEOCAT 2009 network observing several French neonatal medicine and resuscitation services. Key words: newborn, bacteremia, central venous cathete

Geological control of soil organic carbon and nitrogen stocks at the landscape scale

Parent material can deeply influence soil organic matter (SOM) stocks. In this study we tested the hypotheses that parent material had an effect on SOM concentrations and stocks and that this effect may be explained by the influence of soil parent material on basic soil parameters. However, as the factors known to influence SOM stocks such as land use and climate frequently co-vary with geology, testing the influence on SOM stocks of the factor “soil parent material” alone is challenging.To properly test our hypotheses, we studied SOM stocks of forest and cropland soils in a small landscape (17 km2) of the Paris basin (France), i.e. with an homogeneous climate. We collected topsoil samples (0–30 cm) in 50 forest and cropland plots, located in five geological contexts: loess deposit, mudstone, grainstone, chalk and calcareous clay deposits. Basic soil parameters (texture, pH, CaCO3 concentration) and SOM stocks to 30 cm depth (organic C and total N) were determined on the 50 soil samples.Organic C and total N concentrations and stocks in topsoils (0–30 cm) were much higher in forests than in cultivated soils (38.1 (± 12.8) vs. 19.0 (± 4.7) g C kg− 1 soil and 83.4 (± 19.8) vs 48.9 (± 9.9) t C ha− 1 for SOC concentrations and stocks respectively). The influence of land-use on organic C and total N concentrations and stocks was modulated by parent material (significant interactions between land-use and parent material, p < 0.05 for concentrations and stocks). Indeed, the difference in organic C and total N concentrations and stocks in topsoils (0–30 cm) was much lower for soils developed on loess deposits.While SOC concentration was significantly correlated to soil clay concentration for both cropland (r2 = 0.36, p < 0.001) and forest (r2 = 0.44, p < 0.001), there was no significant relation between SOC stocks and soil clay stocks for forest soil (p = 0.11) and a significant but highly scattered positive correlation between SOC and clay stocks in cropland soils (r2 = 0.20, p = 0.02). No significant relation between pH or CaCO3 and SOC stocks was observed. Our results therefore revealed that soil parent material can significantly influence topsoil (0–30 cm) organic C and N stocks but that more research is needed to understand how soil parent material influences SOM stocks as it cannot be simply explained by basic soil physico-chemical parameters (clay and carbonate concentrations or stocks, pH). Overall, our results suggest that a good knowledge of the geology is needed to better constrain SOC stocks as well as SOC stocks evolution in a changing environment from landscape to global scale

Nociceptin/orphanin FQ exacerbates excitotoxic white-matter lesions in the murine neonatal brain

Intracerebral administration of the excitotoxin ibotenate to newborn mice induces white-matter lesions, mimicking brain lesions that occur in human preterm infants. Nociceptin (NC), also called orphanin FQ, is the endogenous ligand of the opioid receptor-like 1 (ORL1) receptor and does not bind classical high-affinity opioid receptors. In the present study, administration of NC exacerbated ibotenate-induced white-matter lesions while coadministration of ibotenate with either of two NC antagonists reduced excitotoxic white-matter lesions by up to 64%. Neither ibotenate plus endomorphin I (a selective μ receptor agonist), nor ibotenate plus naloxone (a classical opioid receptor antagonist) modulated the excitotoxic lesion. Pretreatment with antisense oligonucleotides targeting the NC precursor peptide mRNA significantly reduced ibotenate-induced white-matter damage. Finally, high doses of fentanyl, which stimulates both classical μ opioid receptors and ORL1, exacerbated excitotoxic white-matter lesion. This toxic effect was blocked by inhibiting ORL1 but not classical opioid receptors. Together, these findings show that endogenous or exogenous stimulation of the ORL1 receptor can be neurotoxic and that blocking NC signaling protects the white matter against excitotoxic challenge. These data point to potential new avenues for neuroprotection in human preterm infants at high risk of brain lesions

Ressources pour l’architecture écologique: Tome 1 - Matériaux de construction

International audienceAujourd’hui, les matériaux de construction ne peuvent plus être considérés comme des denrées de consommation, dont l’exploitation n’aurait pour limite que la rentabilité économique.Cet ouvrage, premier d’une série de trois volumes, aborde les enjeux de l’intégration des matériaux à faible impact environnemental (biosourcés, géosourcés et de réemploi) dans le monde de  l’architecture et introduit un nouveau rapport à ces ressources, qui participe d’une relation bilatérale avec notre environnement. Cette approche modifie en profondeur les processus de conception et nous pousse à repenser les méthodes de recherche.Contributions scientifiques, retours d’expériences pédagogiques, exemples d’expérimentations et controverses s’enrichissent mutuellement dans cet ouvrage qui expose toute la dynamique actuelle de la question des ressources en architecture. La pluridisciplinarité et la variété des points de vue montrent la complexité des problèmes, apportent des connaissances et des solutions, ouvrent des perspectives méthodologiques et créatives dans les domaines de l’enseignement, de la recherche et de la pratique sur la question des matériaux écologiques pour la construction