The EIIIA domain from astrocyte-derived fibronectin mediates proliferation of oligodendrocyte progenitor cells following CNS demyelination.

Central nervous system remyelination by oligodendrocyte progenitor cells (OPCs) ultimately fails in the majority of multiple sclerosis (MS) lesions. Remyelination benefits from transient expression of factors that promote migration and proliferation of OPCs, which may include fibronectin (Fn). Fn is present in demyelinated lesions in two major forms; plasma Fn (pFn), deposited following blood-brain barrier disruption, and cellular Fn, synthesized by resident glial cells and containing alternatively spliced domains EIIIA and EIIIB. Here, we investigated the distinctive roles that astrocyte-derived Fn (aFn) and pFn play in remyelination. We used an inducible Cre-lox recombination strategy to selectively remove pFn, aFn or both from mice, and examined the impact on remyelination of toxin-induced demyelinated lesions of spinal cord white matter. This approach revealed that astrocytes are a major source of Fn in demyelinated lesions. Furthermore, following aFn conditional knockout, the number of OPCs recruited to the demyelinated lesion decreased significantly, whereas OPC numbers were unaltered following pFn conditional knockout. However, remyelination completed normally following conditional knockout of aFn and pFn. Both the EIIIA and EIIIB domains of aFn were expressed following demyelination, and in vitro assays demonstrated that the EIIIA domain of aFn mediates proliferation of OPCs, but not migration. Therefore, although the EIIIA domain from aFn mediates OPC proliferation, aFn is not essential for successful remyelination. Since previous findings indicated that astrocyte-derived Fn aggregates in chronic MS lesions inhibit remyelination, aFn removal may benefit therapeutic strategies to promote remyelination in MS.JMJS is recipient of a Junior Scientific Masterclass MD/PhD fellowship from the University Medical Center Groningen. This work was supported by grants from the Netherlands Organization of Scientific Research (NWO, WB, VIDI and Aspasia), the Dutch MS Research Foundation (‘Stichting MS Research’, WB, JMJS, DH), the UK MS Society (CZ, RJMF), and the Research School of Behavioral and Cognitive Neurosciences (BCN, JMJS). Parts of this study were performed at the UMCG Microscopy and Imaging Center (UMIC), which is supported by NWO grants 40-00506-98-9021 and 175-010-2009-023.This is the final version of the article. It was first published by Wiley at http://dx.doi.org/10.1002/glia.2274

Bedaquiline loaded lipid nanoparticles: a promising candidate for TB treatment

Four different kinds of Lipid Nanoparticles (LNP) encapsulating bedaquiline have been tested in order to evaluate the possibility to decrease adverse effects of this very efficient and recent antibiotic. The parameters that are studied among these different types of LNP are the surface charge as well as targeting of macrophages through trimannose groups grafted to the surface. It was found that these nanocarriers could encapsulate bedaquiline with a very high loading efficiency, exhibited a very good colloidal stability in storage conditions as well as in biological media, and an excellent compatibility with animal cells. Finally, first in vivo evaluation showed that these carriers are able to accumulate strongly in the lungs and that the almost neutral ones without targeting ligands could be the best candidate for tuberculosis treatment

Full-disk observations of the Saturn's icy moons by Cassini/VIMS

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Cassini VIMS observations of the Galilean satellites including the VIMS calibration procedure

The Visual and Infrared Mapping Spectrometer (VIMS) observed the Galilean satellites during the Cassini spacecraft's 2000/2001 flyby of Jupiter, providing compositional and thermal information about their surfaces. The Cassini spacecraft approached the jovian system no closer than about 126 Jupiter radii, about 9 million kilometers, at a phase angle of <90°, resulting in only sub-pixel observations by VIMS of the Galilean satellites. Nevertheless, most of the spectral features discovered by the Near Infrared Mapping Spectrometer (NIMS) aboard the Galileo spacecraft during more than four years of observations have been identified in the VIMS data analyzed so far, including a possible 13C absorption. In addition, VIMS made observations in the visible part of the spectrum and at several new phase angles for all the Galilean satellites and the calculated phase functions are presented. In the process of analyzing these data, the VIMS radiometric and spectral calibrations were better determined in preparation for entry into the Saturn system. Treatment of these data is presented as an example of the VIMS data reduction, calibration and analysis process and a detailed explanation is given of the calibration process applied to the Jupiter data