Performances de reproduction et d'élevage des brebis romanov finnoises et croisées: premier bilan des résultats obtenus en france dans les troupeaux expérimentaux de l'INRA et dans quelques troupeaux d'étude

International audienc

Efficacy of Antenatal Corticosteroid Treatment on Neurodevelopmental Outcome according to Head Circumference at Birth

BACKGROUND: There are concerns about the efficacy of antenatal corticosteroid treatment (ACT) in the growth-restricted fetus. OBJECTIVE: To evaluate the effect of ACT on neurodevelopmental outcome at 2 years of corrected age according to the z score of birth head circumference (ZS HC) in a large prospective cohort of preterm infants. METHODS: This study was conducted as a population-based, prospective, multicenter study, including 4,965 infants born between 24 and 33 weeks\u27 gestation and whose status regarding ACT and the measurement of head circumference at birth were available. They were evaluated at 2 years of corrected age to assess neurological outcome. Three approaches were considered to estimate the effect of ACT on neurodevelopment: (i) logistic regression with adjustment on propensity score, (ii) weighted logistic regression using the inverse probability of treatment weighting method, and (iii) 1:1 matching of gestational age, ZS HC, and propensity score between treated and nontreated infants. RESULTS: ACT was documented in 60% of infants. Three groups of infants were considered according to their ZS HC: between -3 and -1 standard deviation (SD), -1 and +1 SD, and +1 and +3 SD, respectively. ACT was associated with a significant improvement of neurodevelopmental outcome only for infants with an ZS HC of between +1 and +3 SD (adjusted OR 1.72; 95% CI 1.06-2.79). Moreover, ORs estimated in the -3 to -1 and +1 to +3 categories were significantly different. CONCLUSION: We found beneficial effects of ACT on neurodevelopmental outcomes at 2 years of corrected age only in preterm infants with a ZS HC >1 SD

Is periventricular heterotopia a useful endpoint for developmental thyroid hormone system disruption in mouse toxicity studies?

Data availability: Data will be made available on request.In rats, hypothyroidism during fetal and neonatal development can disrupt neuronal migration and induce the formation of periventricular heterotopia in the brain. However, it remains uncertain if heterotopia also manifest in mice after developmental hypothyroidism and whether they could be used as a toxicological endpoint to detect TH-mediated effects caused by TH system disrupting chemicals. Here, we performed a mouse study where we induced severe hypothyroidism by exposing pregnant mice (n = 3) to a very high dose of propylthiouracil (PTU) (1500 ppm) in the diet. This, to obtain best chances of detecting heterotopia. We found what appears to be very small heterotopia in 4 out of the 8 PTU-exposed pups. Although the incidence rate could suggest some utility for this endpoint, the small size of the ectopic neuronal clusters at maximum hypothyroidism excludes the utility of heterotopia in mouse toxicity studies aimed to detect TH system disrupting chemicals. On the other hand, parvalbumin expression was manifestly lower in the cortex of hypothyroid mouse offspring demonstrating that offspring TH-deficiency caused an effect on the developing brain. Based on overall results, we conclude that heterotopia formation in mice is not a useful toxicological endpoint for examining TH-mediated developmental neurotoxicity.EU Horizon 2020 programme to two projects: grant number 825161 for the project “ATHENA: Assays for the identification of Thyroid Hormone axis-disrupting chemicals: Elaborating Novel Assessment strategies” (Kortenkamp et al., 2020), and grant number 825753 for the project “ERGO: Breaking Down the Wall Between Human Health and Environmental Testing of Endocrine Disruptors” (Holbech et al., 2020) as well as the Danish Environmental Protection Agency, Ministry of Environment of Denmark

Impact of the Guinea coast upwelling on atmospheric dynamics, precipitation and pollutant transport over southern West Africa

In West Africa, the zonal band of precipitation is generally located around the southern coast in June before migrating northward towards the Sahel in late June/early July. This gives way to a relative dry season for coastal regions from Côte d'Ivoire to Benin called “little dry season”, which lasts until September–October. Previous studies have noted that the coastal rainfall cessation in early July seems to coincide with the emergence of an upwelling along the Guinea coast. The aim of this study is to investigate the mechanisms by which this upwelling impacts precipitation, using a set of numerical simulations performed with the Weather Research and Forecasting regional atmospheric model (WRF v 3.7.1). Sensitivity experiments highlight the response of the atmospheric circulation to an intensification or reduction of the strength of the coastal upwelling. They clearly show that the coastal upwelling emergence is responsible for the cessation of coastal precipitation by weakening the northward humidity transport, thus decreasing the coastal convergence of the humidity transport and inhibiting the deep atmospheric convection. In addition, the diurnal cycle of the low-level circulation plays a critical role: the land breeze controls the seaward convergence of diurnal anomaly of humidity transport, explaining the late night–early morning peak observed in coastal precipitation. The emergence of the coastal upwelling strongly attenuates this peak because of a reduced land–sea temperature gradient in the night and a weaker land breeze. The impact on the inland transport of anthropogenic pollution is also shown with numerical simulations of aerosols using the CHIMERE chemistry-transport model: warmer (colder) sea surface temperature (SST) increases (decreases) the inland transport of pollutants, especially during the night, suggesting an influence of the upwelling intensity on the coastal low-level jet. The mechanisms described have important consequences for inland humidity transport and the predictability of the West African monsoon precipitation in summer.</p

Importance of the Saharan heat low in controlling the North Atlantic free tropospheric humidity budget deduced from IASI <i>δ</i>D observations

The isotopic composition of water vapour in the North Atlantic free troposphere is investigated with Infrared Atmospheric Sounding Interferometer (IASI) measurements of the D ∕ H ratio (δD) above the ocean. We show that in the vicinity of West Africa, the seasonality of δD is particularly strong (130 ‰), which is related with the influence of the Saharan heat low (SHL) during summertime. The SHL indeed largely influences the dynamic in that region by producing deep turbulent mixing layers, yielding a specific water vapour isotopic footprint. The influence of the SHL on the isotopic budget is analysed on various time and space scales and is shown to be large, highlighting the importance of the SHL dynamics on the moistening and the HDO enrichment of the free troposphere over the North Atlantic. The potential influence of the SHL is also investigated on the inter-annual scale as we also report important variations in δD above the Canary archipelago region. We interpret the variability in the enrichment, using backward trajectory analyses, in terms of the ratio of air masses coming from the North Atlantic and air masses coming from the African continent. Finally, the interest of IASI high sampling capabilities is further illustrated by presenting spatial distributions of δD and humidity above the North Atlantic from which we show that the different sources and dehydration pathways controlling the humidity can be disentangled thanks to the added value of δD observations. More generally, our results demonstrate the utility of δD observations obtained from the IASI sounder to gain insight into the hydrological cycle processes in the West African region

Transport of dust particles from the Bodﾃｩlﾃｩ region to the monsoon layer - AMMA case study of the 9-14 June 2006 period

金沢大学フロンティアサイエンス機構Aerosol properties were measured during an airborne campaign experiment that took place in June 2006 in West Africa within the framework of the African Monsoon Multidisciplinary Analyses (AMMA). The goal of the present study was to investigate a dynamical mechanism able to facilitate the sedimentation of dust particles from the Saharan Air Layer (SAL) into the boundary layer. A significant change in the dust particle concentration measured along the meridian between Niamey (Niger) and Cotonou (Benin) was found in the boundary layer (∼700 m), where the dust particle concentration increased in a zone where local emission is not possible. Moreover, the boundary layer top observed with the dropsondes launched with the F-F20 shows a strong relationship with the surface cover anomalies, with higher Boundary Layer (BL) tops over the warmer surfaces, such as croplands, as opposed to adjacent forest. A mesoscale atmospheric model with a new on-line dust parameterization, resulting from the Alfaro and Gomes (2001) parametrisation and AMMA observations, was used to interpret the impact of vegetation anomalies on dust particle sedimentation. The results of the simulation are consistent with the observations, with higher dust concentration over the warm surface cover anomalies. © 2011 Author(s)

Assessing the role of anthropogenic and biogenic sources on PM₁ over southern West Africa using aircraft measurements

As part of the Dynamics-Aerosol-Chemistry-Cloud Interactions in West Africa (DACCIWA) project, an airborne campaign was designed to measure a large range of atmospheric constituents, focusing on the effect of anthropogenic emissions on regional climate. The presented study details results of the French ATR42 research aircraft, which aimed to characterize gas-phase, aerosol and cloud properties in the region during the field campaign carried out in June/July 2016 in combination with the German Falcon 20 and the British Twin Otter aircraft. The aircraft flight paths covered large areas of Benin, Togo, Ghana and Côte d\u27Ivoire, focusing on emissions from large urban conurbations such as Abidjan, Accra and Lomé, as well as remote continental areas and the Gulf of Guinea. This paper focuses on aerosol particle measurements within the boundary layer (<  2000 m), in particular their sources and chemical composition in view of the complex mix of both biogenic and anthropogenic emissions, based on measurements from a compact time-of-flight aerosol mass spectrometer (C-ToF-AMS) and ancillary instrumentation. Background concentrations (i.e. outside urban plumes) observed from the ATR42 indicate a fairly polluted region during the time of the campaign, with average concentrations of carbon monoxide of 131 ppb, ozone of 32 ppb, and aerosol particle number concentration ( >  15 nm) of 735 cm−3 stp. Regarding submicron aerosol composition (considering non-refractory species and black carbon, BC), organic aerosol (OA) is the most abundant species contributing 53 %, followed by SO4 (27 %), NH4 (11 %), BC (6 %), NO3 (2 %) and minor contribution of Cl (<  0.5 %). Average background PM1 in the region was 5.9 µg m−3 stp. During measurements of urban pollution plumes, mainly focusing on the outflow of Abidjan, Accra and Lomé, pollutants are significantly enhanced (e.g. average concentration of CO of 176 ppb, and aerosol particle number concentration of 6500 cm−3 stp), as well as PM1 concentration (11.9 µg m−3 stp). Two classes of organic aerosols were estimated based on C-ToF-AMS: particulate organic nitrates (pONs) and isoprene epoxydiols secondary organic aerosols (IEPOX–SOA). Both classes are usually associated with the formation of particulate matter through complex interactions of anthropogenic and biogenic sources. During DACCIWA, pONs have a fairly small contribution to OA (around 5 %) and are more associated with long-range transport from central Africa than local formation. Conversely, IEPOX–SOA provides a significant contribution to OA (around 24 and 28 % under background and in-plume conditions). Furthermore, the fractional contribution of IEPOX–SOA is largely unaffected by changes in the aerosol composition (particularly the SO4 concentration), which suggests that IEPOX–SOA concentration is mainly driven by pre-existing aerosol surface, instead of aerosol chemical properties. At times of large in-plume SO4 enhancements (above 5 µg m−3), the fractional contribution of IEPOX–SOA to OA increases above 50 %, suggesting only then a change in the IEPOX–SOA-controlling mechanism. It is important to note that IEPOX–SOA constitutes a lower limit to the contribution of biogenic OA, given that other processes (e.g. non-IEPOX isoprene, monoterpene SOA) are likely in the region. Given the significant contribution to aerosol concentration, it is crucial that such complex biogenic–anthropogenic interactions are taken into account in both present-day and future scenario models of this fast-changing, highly sensitive region

Antibody-functionalized polymer-coated gold nanoparticles targeting cancer cells: an in vitro and in vivo study

Gold nanoparticles ( 3c5 nm) coated with plasma-polymerized allylamine were produced through plasma vapor deposition and bioconjugated with a monoclonal antibody targeting the epidermal growth factor receptor. The resulting nanoconjugates displayed an antibody loading of about 1.7 nmol mg -1 and efficiently target epidermal growth factor receptor overexpressing cell lines, as ascertained by ELISA and Western blot assays. The in vitro targeting properties were also confirmed in vivo, where a similar biodistribution profile of what was experienced for the unconjugated antibody was observed. Thanks to the possibility of doping the gold nanoparticles with radionuclides during plasma vapor deposition, the proposed functionalization strategy represents a very suitable platform for the in vivo cancer targeting with nanosized multifunctional particles. This journal is \ua9 2012 The Royal Society of Chemistry

Restoration of Podocyte Structure and Improvement of Chronic Renal Disease in Transgenic Mice Overexpressing Renin

Proteinuria is a major marker of the decline of renal function and an important risk factor of coronary heart disease. Elevated proteinuria is associated to the disruption of slit-diaphragm and loss of podocyte foot processes, structural alterations that are considered irreversible. The objective of the present study was to investigate whether proteinuria can be reversed and to identify the structural modifications and the gene/protein regulation associated to this reversal.We used a novel transgenic strain of mouse (RenTg) that overexpresses renin at a constant high level. At the age of 12-month, RenTg mice showed established lesions typical of chronic renal disease such as peri-vascular and periglomerular inflammation, glomerular ischemia, glomerulosclerosis, mesangial expansion and tubular dilation. Ultrastructural analysis indicated abnormal heterogeneity of basement membrane thickness and disappearance of podocyte foot processes. These structural alterations were accompanied by decreased expressions of proteins specific of podocyte (nephrin, podocin), or tubular epithelial cell (E-cadherin and megalin) integrity. In addition, since TGFbeta is considered the major pro-fibrotic agent in renal disease and since exogenous administration of BMP7 is reported to antagonize the TGFbeta-induced phenotype changes in kidney, we have screened the expressions of several genes belonging in the TGFbeta/BMP superfamily. We found that the endogenous inhibitors of BMPs such as noggin and Usag-1 were several-fold activated inhibiting the action of BMPs and thus reinforcing the deleterious action of TGFbeta.Treatment with an AT1 receptor antagonist, at dose that did not decrease arterial pressure, gradually reduced albuminuria. This decrease was accompanied by re-expression of podocin, nephrin, E-cadherin and megalin, and reappearance of podocyte foot processes. In addition, expressions of noggin and Usag-1 were markedly decreased, permitting thus activation of the beneficial action of BMPs.These findings show that proteinuria and alterations in the expression of proteins involved in the integrity and function of glomerular and renal epithelial phenotype are reversible events when the local action of angiotensin II is blocked, and provide hope that chronic renal disease can be efficiently treated

Genetic Determinants of Circulating Sphingolipid Concentrations in European Populations

Sphingolipids have essential roles as structural components of cell membranes and in cell signalling, and disruption of their metabolism causes several diseases, with diverse neurological, psychiatric, and metabolic consequences. Increasingly, variants within a few of the genes that encode enzymes involved in sphingolipid metabolism are being associated with complex disease phenotypes. Direct experimental evidence supports a role of specific sphingolipid species in several common complex chronic disease processes including atherosclerotic plaque formation, myocardial infarction (MI), cardiomyopathy, pancreatic beta-cell failure, insulin resistance, and type 2 diabetes mellitus. Therefore, sphingolipids represent novel and important intermediate phenotypes for genetic analysis, yet little is known about the major genetic variants that influence their circulating levels in the general population. We performed a genome-wide association study (GWAS) between 318,237 single-nucleotide polymorphisms (SNPs) and levels of circulating sphingomyelin (SM), dihydrosphingomyelin (Dih-SM), ceramide (Cer), and glucosylceramide (GluCer) single lipid species (33 traits); and 43 matched metabolite ratios measured in 4,400 subjects from five diverse European populations. Associated variants (32) in five genomic regions were identified with genome-wide significant corrected p-values ranging down to 9.08 x 10(-66). The strongest associations were observed in or near 7 genes functionally involved in ceramide biosynthesis and trafficking: SPTLC3, LASS4, SGPP1, ATP10D, and FADS1-3. Variants in 3 loci (ATP10D, FADS3, and SPTLC3) associate with MI in a series of three German MI studies. An additional 70 variants across 23 candidate genes involved in sphingolipid-metabolizing pathways also demonstrate association (p = 10(-4) or less). Circulating concentrations of several key components in sphingolipid metabolism are thus under strong genetic control, and variants in these loci can be tested for a role in the development of common cardiovascular, metabolic, neurological, and psychiatric diseases