Adipose tissue mitochondrial dysfunction in human obesity is linked to a specific DNA methylation signature in adipose-derived stem cells

Background: A functional population of adipocyte precursors, termed adipose-derived stromal/stem cells (ASCs), is crucial for proper adipose tissue (AT) expansion, lipid handling, and prevention of lipotoxicity in response to chronic positive energy balance. We previously showed that obese human subjects contain a dysfunctional pool of ASCs. Elucidation of the mechanisms underlying abnormal ASC function might lead to therapeutic interventions for prevention of lipotoxicity by improving the adipogenic capacity of ASCs. Methods: Using epigenome-wide association studies, we explored the impact of obesity on the methylation signature of human ASCs and their differentiated counterparts. Mitochondrial phenotyping of lean and obese ASCs was performed. TBX15 loss- and gain-of-function experiments were carried out and western blotting and electron microscopy studies of mitochondria were performed in white AT biopsies from lean and obese individuals. Results: We found that DNA methylation in adipocyte precursors is significantly modified by the obese environment, and adipogenesis, inflammation, and immunosuppression were the most affected pathways. Also, we identified TBX15 as one of the most differentially hypomethylated genes in obese ASCs, and genetic experiments revealed that TBX15 is a regulator of mitochondrial mass in obese adipocytes. Accordingly, morphological analysis of AT from obese subjects showed an alteration of the mitochondrial network, with changes in mitochondrial shape and number. Conclusions: We identified a DNA methylation signature in adipocyte precursors associated with obesity, which has a significant impact on the metabolic phenotype of mature adipocytes

Towards Validation of SMOS Land Products Using the Synergy Between Models, Airborne and Ground-based Data Over the Valencia Anchor Station. Definition of Matching-up Points to SMOS Observations

Ponencia presentada en el International Geoscience and Remote Sensing Symposium celebrado en Honolulu (Hawaii) del 25 al 30 de julio de 2010López-Baeza et al.The main goal of ESA’s (European Space Agency) SMOS (Soil Moisture and Ocean Salinity) mission is to deliver global fields of surface soil moisture (SM) and sea surface salinity, with enough resolution to be used in numerical weather prediction and global climate models, usin g L-band (1.4 GHz) radiometry. Within the context of the preparation for this mission over land, the Valencia Anchor Station (VAS) experimental site, in Spain, was chosen as a preferential test sites in Europe for SMOS Cal/Val activities. Ground and meteorological measurements over the area are used as input to a Soil-Vegetation-Atmosphere-Transfer (SVAT) model, SURFEX (SURFace EXternalisé) - module ISBA (Interactions between Soil-Biosphere-Atmosphere) to simulate surface SM. Calibration as well as validation of the ISBA model was made by using in situ SM measurements.Peer Reviewe

Athermal metal optics made of nickel plated AlSi40

Metal optics is an inherent part of space instrumentation for years. Diamond turned aluminum (Al6061) mirrors are widely used for application in the mid- and near-infrared (mid-IR and NIR, respectively) spectral range. Aluminum mirrors plated with electroless nickel (NiP) expand the field of application towards multispectral operating instruments down to the ultraviolet wavelengths. Due to the significant mismatch in the coefficient of thermal expansion (CTE) between aluminum and NiP, however, this advantage occurs at the cost of bimetallic bending. Challenging requirements can be met by using bare beryllium or aluminum beryllium composites (AlBeMet) as a CTE tailored substrate material and amorphous NiP as polishable layer. For health reasons, the use of beryllium causes complications in the process chain. Thus, the beryllium approach is subjected to specific applications only. Metal optics has proven to be advantageous in respect of using conventional CNC and ultra-precision fabrication methods to realize complex and light-weighted instrument structures. Moreover, the mirror designs can be effectively optimized for a deterministic system assembly and optimization. Limitations in terms of dimensional stability over temperature and time are mainly given by the inherent material properties (figures of merit) of the substrate material in interaction with the polishing layer. To find an optimal compromise, a thermal matched aluminum-silicon alloy (silicon contents ≈ 40 wt%) plated with NiP (AlSi40/NiP ) was investigated in a joined project of the Max Planck Institute for Astronomy MPIA and the Fraunhofer Institute for Applied Optics and Precision Engineering IOF. The main tasks of the project were the minimization of the bimetallic bending, the development of reliable stabilizing and aging procedures, and the establishment of a proven fabrication method. This paper describes fundamental results regarding the optimization of the athermal material combination. Furthermore, the developed production chain for high quality freeform mirrors made of AlSi40/NiP is pointed out

Allosteric inhibition of Taspase1's pathobiological activity by enforced dimerization in vivo

Taspase1 mediates cleavage of the mixed lineage leukemia (MLL) protein and leukemia-provoking MLL fusions and promotes solid malignancies. Currently, no effective and specific Taspase1 inhibitors are available, precluding its therapeutic exploitation. As the Taspase1 proenzyme is autoproteolytically cleaved and assumed to assemble into an active alpha beta beta alpha heterodimer, we attempted to interfere with its activity by targeting Taspase1's dimerization. Notably, enforced expression of inactive Taspase1 mutants, aiming to inhibit formation of active protease dimers, was not inhibitory. Immunoprecipitation, gel filtration, and in vivo protein interaction assays revealed that active Taspase1 exists predominantly as an alpha beta monomer in living cells, providing an explanation why overexpression of inactive mutants was not trans-dominant. To alternatively test the biological consequences of enforced dimerization, we engineered Taspase1 variants containing the Jun/Fos dimerization motif. In absence of the respective interaction partners, the protease fusions were fully active, while enforcing dimerization by coexpression significantly inhibited processing of several target proteins in living cells. Our study provides the first evidence that Taspase1 is already active as an alpha beta monomer, arguing against heterocomplex formation being required for its pathobiological activity. Thus, it clearly supports strategies aiming to inhibit the cancer-promoting activity of Taspase1 by the identification of chemical decoys enforcing its dimerization.-Bier, C., Knauer, S. K., Wunsch, D., Kunst, L., Scheiding, S., Kaiser, M., Ottmann, C., Kramer, O. H., Stauber, R. H. Allosteric inhibition of Taspase1's pathobiological activity by enforced dimerization in vivo. FASEB J. 26, 3421-3429 (2012). www.fasebj.or

CNES and ESA CAROLS Airborne Campaigns at the Valencia Anchor Station in the framework of SMOS Validation

Wigneron et al.Ponencia presentada en la 38th COSPAR Scientific Assembly celebrada en Brema (Alemania) del 18 al 25 de julio de 2010This communication will present the main results of a series of airborne campaigns conducted at the Valencia Anchor Station (VAS) site for the implementation of the SMOS emission model L-MEB (L-band Microwave Emission model of the Biosphere, Wigneron et al., 2007), in the framework of the validation of SMOS land data and products. CNES CAROLS campaigns: In 2009, the L-band CAROLS (Combined Airborne Radio-instruments for Ocean and Land Studies) radiometer was flown on three occasions over an area of 1500 km2 covering vineyards, shrub land and Mediterranean pine forest. Main results of CAROLS 2009 will be presented in this communication, and the emphasis will be on comparing local to regional scale results given that CAROLS flights were performed at 4000 m above the surface. ESA-CNES CAROLS campaigns: In 2010, the L-band CAROLS radiometer was flown on four occasions over an area of about 20 km x 20 km containing a large number of homogeneous units (`environmental units'), with flight lines performed at approximately 2200 m above sea level and in alternate E-W and W-E directions in order to have multi-angular signatures over the same area, and avoid potential RFI in Western Spain. The preliminary results of this campaign will be presented in this communication, and the emphasis will be the validation of the L-MEB model.Peer Reviewe

Anamorphotic telescope for earth observation in the mid-infrared range

In the framework of the “Earth Explorer” program, the European Space Agency had foreseen the PREMIER mission intended to monitor the three-dimensional distribution of trace gasses in the atmosphere