8 research outputs found
Stereochemistry of Spiro-Acetalized [60]Fullerenes: How the <i>Exo</i> and <i>Endo</i> Stereoisomers Influence Organic Solar Cell Performance
Exploiting bis-addition products
of fullerenes is a rational way to improve the efficiency of bulk
heterojunction-type organic photovoltaic cells (OPV); however, this
design inherently produces regio- and stereoisomers that may impair
the ultimate performance and fabrication reproducibility. Here, we
report unprecedented <i>exo</i> and <i>endo</i> stereoisomers of the spiro-acetalized [60]Âfullerene monoadduct with
methyl- or phenyl-substituted 1,3-dioxane (<b>SAF</b><sub><b>6</b></sub>). Although there is no chiral carbon in either the
reagent or the fullerene, equatorial (<i>eq</i>) rather
than axial (<i>ax</i>) isomers are selectively produced
at an <i>exo-eq</i>:<i>endo</i>-<i>eq</i> ratio of approximately 1:1 and can be easily separated using silica
gel column chromatography. Nuclear Overhauser effect measurements
identified the conformations of the straight <i>exo</i> isomer
and bent <i>endo</i> isomer. We discuss the origin of stereoselectivity,
the anomeric effect, intermolecular ordering in the film state, and
the performance of polyÂ(3-hexylthiophene):substituted <b>SAF</b><sub><b>6</b></sub> OPV devices. Despite their identical optical
and electrochemical properties, their solubilities and space-charge
limited current mobilities are largely influenced by the stereoisomers,
which leads to variation in the OPV efficiency. This study emphasizes
the importance of fullerene stereochemistry for understanding the
relationship between stereochemical structures and device output
Image_1_Amyloid Beta Is Internalized via Macropinocytosis, an HSPG- and Lipid Raft-Dependent and Rac1-Mediated Process.TIFF
Intracellular amyloid β peptide (Aβ) accumulation has drawn attention in relation to the pathophysiology of Alzheimer’s disease in addition to its extracellular deposition as senile plaque. Cellular uptake of extracellular Aβ is one of the possible mechanisms by which intracellular Aβ deposits form. Given the relevance of Aβ inside cells, it is important to understand the mechanism by which it is taken up by them. In this study, we elucidated that Neuro2A and SH-SY5Y cells internalize specifically oligomerized Aβ in a time- and dose-dependent manner. The depletion of plasma membrane cholesterol with methyl-β-cyclodextrin or treatment with trypsin diminished the internalization of oAβ, suggesting that the oAβ uptake might be both a lipid raft-dependent and heparan sulfate proteoglycan-mediated process. Treatment with a macropinocytosis inhibitor (ethylisopropyl amiloride and wortmannin) also drastically reduced the uptake of oligomer-Aβ (oAβ). oAβ-treated cells exhibited an increase in Rac1 activity, indicating that macropinocytosis induced by oAβ is regulated by these small GTPases. These findings suggest that macropinocytosis is a major endocytic route through which oAβ42 enters cells.</p
Image_2_Amyloid Beta Is Internalized via Macropinocytosis, an HSPG- and Lipid Raft-Dependent and Rac1-Mediated Process.TIFF
Intracellular amyloid β peptide (Aβ) accumulation has drawn attention in relation to the pathophysiology of Alzheimer’s disease in addition to its extracellular deposition as senile plaque. Cellular uptake of extracellular Aβ is one of the possible mechanisms by which intracellular Aβ deposits form. Given the relevance of Aβ inside cells, it is important to understand the mechanism by which it is taken up by them. In this study, we elucidated that Neuro2A and SH-SY5Y cells internalize specifically oligomerized Aβ in a time- and dose-dependent manner. The depletion of plasma membrane cholesterol with methyl-β-cyclodextrin or treatment with trypsin diminished the internalization of oAβ, suggesting that the oAβ uptake might be both a lipid raft-dependent and heparan sulfate proteoglycan-mediated process. Treatment with a macropinocytosis inhibitor (ethylisopropyl amiloride and wortmannin) also drastically reduced the uptake of oligomer-Aβ (oAβ). oAβ-treated cells exhibited an increase in Rac1 activity, indicating that macropinocytosis induced by oAβ is regulated by these small GTPases. These findings suggest that macropinocytosis is a major endocytic route through which oAβ42 enters cells.</p
Subject characteristics.
<p>s-IBM, sporadic inclusion body myositis; DMRV, distal myopathy with rimmed vacuoles; F, female; M, male</p
Representative confocal laser scanning micrograph.
<p>Double immunofluorescence labeling and merged images in muscle sections from patients with s-IBM for CHMP2B (green) and pTDP43 (red) (A), caspase3 (green) and pTDP43 (red) (B), CDK5 (green) and pTDP43 (red) (C), CK1δ (green) and pTDP43 (red) (D), JNK (green) and pTDP43 (red) (E), LRRK2 (green) and pTDP43 (red) (F), annexin 2 (green) and pTDP43 (red) (G), and flotillin-1 (green) and pTDP43 (red) (H). Arrows indicate RVs. Scale bar  = 20 µm.</p
Immunohistochemistry for GVD markers in muscle fibers of s-IBM cases.
<p>Anti-CHMP2B (A), anti-caspase3 (B, C), anti-CDK5 (D), anti- CK1δ (E, F), anti-JNK (G, H), anti-LRRK2 (I), anti-annexin2 (J, K), anti-flotillin-1 (L, M), and anti-pTDP43 (N, O). (B, C), (E, F), (G,H), (J, K), (L, M) and (N, O) indicate 2 independent antibodies for the identification of each protein. Arrows indicate RVs. Scale bar  = 20 µm.</p
Immunohistochemistry for CHMP2B in muscle fibers of s-IBM and DMRV cases.
<p>RVs in all s-IBM (A–C) and distal myopathy with RVs (DMRV) (D) cases detected by anti- CHMP2B antibody. Arrows indicate RVs. Scale bar  = 20 µm.</p