Alexander disease is a primary genetic disorder of astrocyte caused by dominant mutations in the astrocyte-specific intermediate filament glial fibrillary acidic protein (GFAP). While most of the disease-causing mutations described to date have been found in the conserved α-helical rod domain, some mutations are found in the C-terminal non-α-helical tail domain. Here, we compare five different mutations (N386I, S393I, S398F, S398Y and D417M14X) located in the C-terminal domain of GFAP on filament assembly properties in vitro and in transiently transfected cultured cells. All the mutations disrupted in vitro filament assembly. The mutations also affected the solubility and promoted filament aggregation of GFAP in transiently transfected MCF7, SW13 and U343MG cells. This correlated with the activation of the p38 stress-activated protein kinase and an increased association with the small heat shock protein (SHSP) chaperone, αB-crystallin. Of the mutants studied, D417M14X GFAP caused the most significant effects both upon filament assembly in vitro and in transiently transfected cells. This mutant also caused extensive filament aggregation coinciding with the sequestration of αB-crystallin and HSP27 as well as inhibition of the proteosome and activation of p38 kinase. Associated with these changes were an activation of caspase 3 and a significant decrease in astrocyte viability. We conclude that some mutations in the C-terminus of GFAP correlate with caspase 3 cleavage and the loss of cell viability, suggesting that these could be contributory factors in the development of Alexander disease.
A variety of crystalline colloid binary halide, ternary perovskite-like and ternary perovskite-derivative nanostructures with well-defined morphologies were synthesized, thus expanding materials chemistry to the new category of nanomaterials. The optical and photocatalytic properties of ternary nanostructures were investigated.
GePt3 and Ge2Pt nanoparticles were synthesized via a solution colloidal method as catalysts for dye-sensitized solar cells (DSSC) and the hydrogen evolution reaction (HER). The shape, size, arrangement, phases and crystalline structures of Ge-Pt nanoparticles were determined, and the ability to be dispersed in nonpolar solvents enabled them to form a catalyst ink with a stable ejection for the spray coating technique. A series of electrochemical analyses confirmed the catalytic properties of Ge-Pt nanoparticles toward the I-/I3- redox reaction system. The DSSC using GePt3 nanoparticles as the counter electrode exhibited excellent power conversion efficiency (PCE) of 8.04% at 0.16 cm2, which was comparable to that of a DSSC using Pt as the counter electrode (8.0%); it also exhibited an average PCE of 7.26% even at a large working area (2 cm2). In addition, the GePt3 catalyst exhibited excellent HER electrocatalytic performance with a large current density and a low Tafel slope, and it could stably operate at a working area of up to 5 cm2 with a low over potential (<0.06 V) to achieve 10 mA cm-2 cathodic current. This study provides fundamental insights into the preparation of germanium-platinum intermetallic compound catalysts at the nanoscale, which can be beneficial for the design and development of clean energy devices.
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