Direct Analysis of Mitochondrial Damage Caused by Misfolded/Destabilized Proteins

Protein quality control is essential for cellular homeostasis. In this study, we examined the effect of improperly folded proteins that do not form amyloid fibrils on mitochondria, which play important roles in ATP production and cell death. First, we prepared domain 3 of the dengue envelope protein in wild type and four mutants with widely different biophysical properties in misfolded/aggregated or destabilized states. The effects of the different proteins were detected using fluorescence microscopy and Western blotting, which revealed that three of the five proteins disrupted both inner and outer membrane integrity, while the other two proteins, including the wild type, did not. Next, we examined the common characteristics of the proteins that displayed toxicity against mitochondria by measuring oligomer size, molten globule-like properties, and thermal stability. The common feature of all three toxic proteins was thermal instability. Therefore, our data strongly suggest that thermally unstable proteins generated in the cytosol can cause cellular damage by coming into direct contact with mitochondria. More importantly, we revealed that this damage is not amyloid-specific.     

MC180295 Inhibited Epstein–Barr Virus-Associated Gastric Carcinoma Cell Growth by Suppressing DNA Repair and the Cell Cycle

DNA methylation of both viral and host DNA is one of the major mechanisms involved in the development of Epstein–Barr virus-associated gastric carcinoma (EBVaGC); thus, epigenetic treatment using demethylating agents would seem to be promising. We have verified the effect of {"type":"entrez-nucleotide","attrs":{"text":"MC180295","term_id":"1885105835","term_text":"MC180295"}}MC180295, which was discovered by screening for demethylating agents. {"type":"entrez-nucleotide","attrs":{"text":"MC180295","term_id":"1885105835","term_text":"MC180295"}}MC180295 inhibited cell growth of the EBVaGC cell lines YCCEL1 and SNU719 in a dose-dependent manner. In a cell cycle analysis, growth arrest and apoptosis were observed in both YCCEL1 and SNU719 cells treated with {"type":"entrez-nucleotide","attrs":{"text":"MC180295","term_id":"1885105835","term_text":"MC180295"}}MC180295. MKN28 cells infected with EBV were sensitive to {"type":"entrez-nucleotide","attrs":{"text":"MC180295","term_id":"1885105835","term_text":"MC180295"}}MC180295 and showed more significant inhibition of cell growth compared to controls without EBV infection. Serial analysis of gene expression analysis showed the expression of genes belonging to the role of BRCA1 in DNA damage response and cell cycle control chromosomal replication to be significantly reduced after {"type":"entrez-nucleotide","attrs":{"text":"MC180295","term_id":"1885105835","term_text":"MC180295"}}MC180295 treatment. We confirmed with quantitative PCR that the expression levels of BRCA2, FANCM, RAD51, TOP2A, and CDC45 were significantly decreased by {"type":"entrez-nucleotide","attrs":{"text":"MC180295","term_id":"1885105835","term_text":"MC180295"}}MC180295. LMP1 and BZLF1 are EBV genes with expression that is epigenetically regulated, and {"type":"entrez-nucleotide","attrs":{"text":"MC180295","term_id":"1885105835","term_text":"MC180295"}}MC180295 could up-regulate their expression. In conclusion, {"type":"entrez-nucleotide","attrs":{"text":"MC180295","term_id":"1885105835","term_text":"MC180295"}}MC180295 inhibited the growth of EBVaGC cells by suppressing DNA repair and the cell cycle.     

Low temperature synthesis of silver-palladium alloy powders internal electrodes for multilayer ceramic devices

Physical and electrical properties of three types of Ag-Pd pastes, which consist of different metal fine powders, i.e., a coprecipitated powder, an agglomerated alloy powder made by heat treatment and a pulverized alloy powder produced by improved pulverization method, have been studied. The paste prepared from pulverized alloy powder showed a higher film packing density (6.3 g/cm³) than those made of the other powders. The film consisting of pulverized alloy powder showed a lower expansion at around 500 °C, a lower shrinkage from 700 °C to 1100 °C and a lower electric resistivity. The results indicated that the paste which consists of an pulverized Ag-Pd alloy powder was superior in performance to the other two pastes for an internal electrode material of multilayer ceramic device.     

Structure and kinetic studies of U(VI)-benzamidoxime complex in non-aqueous solutions by H- and C-NMR

The structural and kinetic studies of U(VI) complex with benzamidoxime(Hba) as ligand in CD₃COCD₃ have been studied by means of ¹H and ¹³C NMR. The Hba molecule was found to coordinate to UO₂²⁺ in the form of anionic benzamidoximate (ba), and the number of ba coordinated to UO₂²⁺ was determined to be 3 by analyzing the chemical shift of ¹³C NMR signal for Hba in the presence of UO₂²⁺. The exchange rate constants(k_ex) of ba in [UO₂(ba)₃] were determined by the NMR line-broadening method. The kinetic parameters were obtained as follows: k_ex(25°C) = 3.1 × 10³s⁻¹, ΔH^≠ = 35.8 ± 3.5 KJ mol⁻¹, and ΔS^≠ = −65 ± 13.7 J K⁻¹ mol⁻¹. The UV-visible absorption spectra of solutions containing UO₂²⁺ and Hba were also measured. The molar extinction coefficient of the complex was found to be extremely large compared with those of UO₂(L)₅²⁺ (L = unidentate oxygen donor ligands) complexes. This is due to the strong electron withdrawing of UO₂²⁺ from Hba and suggests that an interaction between UO₂²⁺ and Hba is very strong. Such a high affinity of monomeric amidoxime to UO₂²⁺ reasonably explains the high adsorptibility of amidoxime resin to U(VI) species, and is considered to result in the high recovery of U(VI) species from sea water using amidoxime resin.     

Colorectal Laterally Spreading Tumors by Computed Tomographic Colonography

To date, few reports focused primarily on detecting colorectal laterally spreading tumors (LSTs) have been published. The aim of this study was to determine the visibility of LSTs on computed tomographic colonography (CTC) compared with that on colonoscopy as a standard. We retrospectively reviewed and matched data on endoscopic and CTC reports in 157 patients (161 LSTs) who received a multidetector CT scan using contrast media immediately after total colonoscopy at the National Cancer Center Hospital in Tokyo, Japan, between December 2005 and August 2010. The results of the total colonoscopy were known at the time of the CTC procedure and reading. Of the 161 LSTs detected on colonoscopy, 138 were observed and matched by CTC (86%). Of the 91 granular type LSTs (LST-Gs), 88 (97%) were observed and matched, while of the 70 non-granular type LSTs (LST-NGs), 50 (71%) were observed and matched by CTC (p < 0.0001). CTC enabled observation of 73% (22/30) of 20–29 mm, 83% (35/42) of 30–39 mm, 88% (49/56) of 40–59 mm, and 97% (32/33) of ≥60 mm tumors. The rate of observed LSTs by CTC was 86% (97% of LST-G, 71% of LST-NG) of the LSTs found during total colonoscopy.     

Profile structure of magnetic flux lines in type-II superconductor from a rectangular electron hologram

Profile magnetic configuration of a quantized flux line and flux-line lattice penetrating a type-II superconductor thin foil, niobium, was observed by electron holography and Lorentz microscopy using a 300 kV field-emission electron microscope. Each single flux line was distributed periodically as lattice structure in the mixed state just below its critical temperature of 8.5 K, while at low temperature of 5 K the flux lines were weakly bound as bundles. In order to observe the flux-line distribution over a wide area, discrete Fourier transform reconstruction in the holography was extended for a rectangular area without loss of information and data precision.     

Uptake by macrophages of low-density lipoprotein damaged by nitrogen dioxide in air

In order to know whether nitrogen dioxide, an environmental and endogenous free radical toxin, can participate in the formation of atherosclerotic lesions, damage to low-density lipoprotein (LDL) by nitrogen dioxide and uptake of the damaged LDL by macrophages were investigated. A solution of LDL at pH 7.5 was exposed to an atmosphere of nitrogen dioxide (70 ppm) in air at 37°C for 5 or 10 h. Lipid oxidation was induced by the exposure as assessed by the formation of thiobarbituric acid reactive substances. Apolipoprotein B was covalently cross-linked via nondisulfide bonds. Fluorescence analysis showed that tryptophan residues were extensively decreased, and amino acid analysis indicated that the contents of histidine, lysine, and tyrosine residues were decreased by 30–40, 10–20, and 20–30%, respectively. Binding of LDL to thioglycolate-induced mouse peritoneal macrophages was markedly increased by the exposure as observed by the binding of mouse erythrocytes coated with LDL. The activity of LDL to convert macrophages into lipid-laden foam cells was also increased by the exposure. Modification of lysine residues of apo B with lipid oxidation products formed by the exposure may be responsible for the uptake by macrophages. The results suggest the possibility that exposure of LDLin vivo to nitrogen dioxide participates in the formation of atherosclerotic lesions.     

Multiple evaluations of the removal of pollutants in road runoff by soil infiltration

Groundwater replenishment by infiltration of road runoff is expected to be a promising option for ensuring a sustainable urban water cycle. In this study, we performed a soil infiltration column test using artificial road runoff equivalent to approximately 11-12 years of rainfall to evaluate the removal of pollutants by using various chemical analyses and bioassay tests. These results indicated that soil infiltration treatment works effectively to remove most of the pollutants such as organic matter (chemical oxygen demand (CODMn) and dissolved organic carbon (DOC)), P species, polycyclic aromatic hydrocarbons (PAHs), numerous heavy metals and oestrogenic activities. Bioassay tests, including algal growth inhibition test, Microtox and mutagen formation potential (MFP) test, also revealed effective removal of toxicities by the soils. However, limited amounts of NO3, Mn, Ni, alkaline earth metals, perfluorooctane sulphonate (PFOS) and perfluorooctane sulphonamide (FOSA) were removed by the soils and they possibly reach the groundwater and cause contamination.     

Bendability of aluminiumand steel-clad chromium plates

The present paper describes how the cladding of chromium plate with dissimilar metals improves the plastic bendability of the chromium. Three-point bending tests at various temperatures were performed for three types of chromium specimens: a monolithic chromium plate, aluminium- and steel-clad chromium plate. The aluminium-clad chromium plate was bent at 343 K up to a bent angle of 90 degrees without failure, even when the chromium layer was located outside of the plate (tension side), while the monolithic chromium plate could be bent exclusively at temperatures above 403 K. When the chromium layer was located inside of the steel-clad chromium plate (compression side), the plate was successfully bent at 307 K. The FE stress analysis of bending proved that the cladding of chromium plates with proper metals of different kinds is effective to reduce the tensile stress in chromium induced during bending and also the residual stress existing after bending operation.     

Full scale investigation of GCL damage mechanisms in small earth dam retrofit applications under earthquake loading

This paper reports results of full scale testing to further explore potential GCL damage mechanisms in earth dam retrofit applications in seismically active areas; in particular, to a) investigate whether shear displacements could reduce the magnitude of GCL panel overlap during earthquake shaking; b) explore the influence of gravel particles on GCL thickness at localised point of contact; and c) observe the consequences of an accidental exposure of an uncovered GCL to short duration rainfall in terms of moisture content and effects during subsequent compaction. The results of these experiments indicate that even under severe shaking no movements were detected at the GCL panel overlap. Whereas gravel particles were observed to locally reduce the thickness of the GCL to 2.2 mm, no plowing of the particle into the GCL occurred due to a lack of shear displacement at the interface, resulting in no localised internal erosion through the barrier. Furthermore, hydration of GCL panels during construction due to surface wetting was observed to result in a state of hydration less than its post-construction state. These results indicate that although each of the three GCL damage mechanisms cannot be ruled out to ever be relevant in practice, the performance of the GCL retrofitted earth dam tested was satisfactory under even severe Level 2 earthquake shaking, and suggests that the retrofitting of small earth dams with GCLs is a promising strategy to improve their static and seismic resistance.