Evolutionary Analysis of Mitogenomes from Parasitic and Free-Living Flatworms

Copyright: © 2015 Solà et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. The attached file is the published version of the article

The effect of dexamethasone on defective nephrin transport caused by ER stress: A potential mechanism for the therapeutic action of glucocorticoids in the acquired glomerular diseases

The mechanism by which glucocorticoids govern antiproteinuric effect in nephrotic syndrome remains unknown. Present study examined the protective role of dexamethasone (DEX) in the intracellular trafficking of nephrin under endoplasmic reticulum (ER) stress. Human embryonic kidney-293 cell line expressing a full-length human nephrin was cultured in mediums containing 5.5 or 25 mM glucose with or without DEX. The result revealed that glucose starvation evoked a rapid ER stress leading to formation of underglycosylated nephrin that was remained in the ER as a complex with calreticulin/calnexin. DEX rescued this interfered trafficking through binding to its receptor and stimulating the mitochondrial transcripts and adenosine 5′ triphosphate (ATP) production, leading to synthesis of fully glycosylated nephrin. These results suggest that ER-stress in podocytes may cause alteration of nephrin N-glycosylation, which may be an underlying factor in the pathomechanism of the proteinuria in nephrotic syndrome. DEX may restore this imbalance by stimulating expression of mitochondrial genes, resulted in the production of ATP that is essential factor for proper folding machinery aided by the ER chaperones

Blockade of T-cell activation by dithiocarbamates involves novel mechanisms of inhibition of nuclear factor of activated T cells.

Dithiocarbamates (DTCs) have recently been reported as powerful inhibitors of NF-kappaB activation in a number of cell types. Given the role of this transcription factor in the regulation of gene expression in the inflammatory response, NF-kappaB inhibitors have been suggested as potential therapeutic drugs for inflammatory diseases. We show here that DTCs inhibited both interleukin 2 (IL-2) synthesis and membrane expression of antigens which are induced during T-cell activation. This inhibition, which occurred with a parallel activation of c-Jun transactivating functions and expression, was reflected by transfection experiments at the IL-2 promoter level, and involved not only the inhibition of NF-kappaB-driven reporter activation but also that of nuclear factor of activated T cells (NFAT). Accordingly, electrophoretic mobility shift assays (EMSAs) indicated that pyrrolidine DTC (PDTC) prevented NF-kappaB, and NFAT DNA-binding activity in T cells stimulated with either phorbol myristate acetate plus ionophore or antibodies against the CD3-T-cell receptor complex and simultaneously activated the binding of AP-1. Furthermore, PDTC differentially targeted both NFATp and NFATc family members, inhibiting the transactivation functions of NFATp and mRNA induction of NFATc. Strikingly, Western blotting and immunocytochemical experiments indicated that PDTC promoted a transient and rapid shuttling of NFATp and NFATc, leading to their accelerated export from the nucleus of activated T cells. We propose that the activation of an NFAT kinase by PDTC could be responsible for the rapid shuttling of the NFAT, therefore transiently converting the sustained transactivation of this transcription factor that occurs during lymphocyte activation, and show that c-Jun NH2-terminal kinase (JNK) can act by directly phosphorylating NFATp. In addition, the combined inhibitory effects on NFAT and NF-KB support a potential use of DTCs as immunosuppressants

Magnetic Reconnection in Extreme Astrophysical Environments

Magnetic reconnection is a basic plasma process of dramatic rearrangement of magnetic topology, often leading to a violent release of magnetic energy. It is important in magnetic fusion and in space and solar physics --- areas that have so far provided the context for most of reconnection research. Importantly, these environments consist just of electrons and ions and the dissipated energy always stays with the plasma. In contrast, in this paper I introduce a new direction of research, motivated by several important problems in high-energy astrophysics --- reconnection in high energy density (HED) radiative plasmas, where radiation pressure and radiative cooling become dominant factors in the pressure and energy balance. I identify the key processes distinguishing HED reconnection: special-relativistic effects; radiative effects (radiative cooling, radiation pressure, and Compton resistivity); and, at the most extreme end, QED effects, including pair creation. I then discuss the main astrophysical applications --- situations with magnetar-strength fields (exceeding the quantum critical field of about 4 x 10^13 G): giant SGR flares and magnetically-powered central engines and jets of GRBs. Here, magnetic energy density is so high that its dissipation heats the plasma to MeV temperatures. Electron-positron pairs are then copiously produced, making the reconnection layer highly collisional and dressing it in a thick pair coat that traps radiation. The pressure is dominated by radiation and pairs. Yet, radiation diffusion across the layer may be faster than the global Alfv\'en transit time; then, radiative cooling governs the thermodynamics and reconnection becomes a radiative transfer problem, greatly affected by the ultra-strong magnetic field. This overall picture is very different from our traditional picture of reconnection and thus represents a new frontier in reconnection research.Comment: Accepted to Space Science Reviews (special issue on magnetic reconnection). Article is based on an invited review talk at the Yosemite-2010 Workshop on Magnetic Reconnection (Yosemite NP, CA, USA; February 8-12, 2010). 30 pages, no figure

Osteoinduction in human fat derived stem cells by recombinant human bone morphogenetic protein-2 produced in Escherichia coli

Bioactive recombinant human bone morphogenetic protein-2 (rhBMP-2) was obtained using Escherichia coli pET-25b expression system: 55 mg purified rhBMP-2 were achieved per g cell dry wt, with up to 95% purity. In murine C2C12 cell line, rhBMP-2 induced an increase in the transcription of Smads and of osteogenic markers Runx2/Cbfa1 and Osterix, measured by semi-quantitative RT-PCR. Bioassays performed in human fat-derived stem cells showed an increased activity of the early osteogenic marker, alkaline phosphatase, and the absence of cytotoxicity