ESA's wind Lidar mission ADM-AEOLUS; on-going scientific activities related to calibration, retrieval and instrument operation

The Earth Explorer Atmospheric Dynamics Mission (ADM-Aeolus) of ESA will be the first-ever satellite to provide global observations of wind profiles from space. Its single payload, namely the Atmospheric Laser Doppler Instrument (ALADIN) is a directdetection high spectral resolution Doppler Wind Lidar (DWL), operating at 355 nm, with a fringe-imaging receiver (analysing aerosol and cloud backscatter) and a double-edge receiver (analysing molecular backscatter). In order to meet the stringent mission requirements on wind retrieval, ESA is conducting various science support activities for the consolidation of the on-ground data processing, calibration and sampling strategies. Results from a recent laboratory experiment to study Rayleigh-Brillouin scattering and improve the characterisation of the molecular lidar backscatter signal detected by the ALADIN double-edge Fabry- Perot receiver will be presented in this paper. The experiment produced the most accurate ever-measured Rayleigh-Brillouin scattering profiles for a range of temperature, pressure and gases, representative of Earth’s atmosphere. The measurements were used to validate the Tenti S6 model, which is implemented in the ADM-Aeolus ground processor. First results from the on-going Vertical Aeolus Measurement Positioning (VAMP) study will be also reported. This second study aims at the optimisation of the ADM-Aeolus vertical sampling in order to maximise the information content of the retrieved winds, taking into account the atmospheric dynamical and optical heterogeneity. The impact of the Aeolus wind profiles on Numerical Weather Prediction (NWP) and stratospheric circulation modelling for the different vertical sampling strategies is also being estimated

NQO1-Dependent Redox Cycling of Idebenone: Effects on Cellular Redox Potential and Energy Levels

Short-chain quinones are described as potent antioxidants and in the case of idebenone have already been under clinical investigation for the treatment of neuromuscular disorders. Due to their analogy to coenzyme Q10 (CoQ10), a long-chain quinone, they are widely regarded as a substitute for CoQ10. However, apart from their antioxidant function, this provides no clear rationale for their use in disorders with normal CoQ10 levels. Using recombinant NAD(P)H:quinone oxidoreductase (NQO) enzymes, we observed that contrary to CoQ10 short-chain quinones such as idebenone are good substrates for both NQO1 and NQO2. Furthermore, the reduction of short-chain quinones by NQOs enabled an antimycin A-sensitive transfer of electrons from cytosolic NAD(P)H to the mitochondrial respiratory chain in both human hepatoma cells (HepG2) and freshly isolated mouse hepatocytes. Consistent with the substrate selectivity of NQOs, both idebenone and CoQ1, but not CoQ10, partially restored cellular ATP levels under conditions of impaired complex I function. The observed cytosolic-mitochondrial shuttling of idebenone and CoQ1 was also associated with reduced lactate production by cybrid cells from mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS) patients. Thus, the observed activities separate the effectiveness of short-chain quinones from the related long-chain CoQ10 and provide the rationale for the use of short-chain quinones such as idebenone for the treatment of mitochondrial disorders

Human and experimental evidence supporting a role for osteopontin in alcoholic hepatitis: Hepatology

We identified in the transcriptome analysis of patients with alcoholic hepatitis (AH) osteopontin (OPN) as one of the most up-regulated genes. Here, we used a translational approach to investigate its pathogenic role. OPN hepatic gene expression was quantified in patients with AH and other liver diseases. OPN protein expression and processing were assessed by immmunohistochemistry, Western blotting and ELISA. OPN gene polymorphisms were evaluated in patients with alcoholic liver disease. The role of OPN was evaluated in OPN−/− mice with alcohol-induced liver injury. OPN biological actions were studied in human hepatic stellate cells and in precision-cut liver slices. Hepatic expression and serum levels of OPN were markedly increased in AH compared to normal livers and other types of chronic liver diseases and correlated with short-term survival. Serum levels of OPN also correlated with hepatic expression and disease severity. OPN was mainly expressed in areas with inflammation and fibrosis. Two proteases that process OPN (thrombin and MMP-7) and cleaved-OPN were increased in livers with AH. Patients with AH had a tendency of a lower frequency of the CC genotype of the +1239C SNP of the OPN gene compared to patients with alcohol abuse without liver disease. Importantly, OPN−/− mice were protected against alcohol-induced liver injury and showed decreased expression of inflammatory cytokines. Finally, OPN was induced by LPS and stimulated inflammatory actions in hepatic stellate cells

Early recovery of cognitive impairments during withdrawal in patients with alcohol dependence

32nd Congress of the European-College-of-Neuropsychopharmacology (ECNP), Copenhagen, DENMARK, SEP 07-10, 2019International audienc