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.     

Human Chorionic Villous Differentiation and Placental Development

In humans, the placenta provides the only fetomaternal connection and is essential for establishing a pregnancy as well as fetal well-being. Additionally, it allows maternal physiological adaptation and embryonic immunological acceptance, support, and nutrition. The placenta is derived from extra-embryonic tissues that develop rapidly and dynamically in the first weeks of pregnancy. It is primarily composed of trophoblasts that differentiate into villi, stromal cells, macrophages, and fetal endothelial cells (FEC). Placental differentiation may be closely related to perinatal diseases, including fetal growth retardation (FGR) and hypertensive disorders of pregnancy (HDP), and miscarriage. There are limited findings regarding human chorionic villous differentiation and placental development because conducting in vivo studies is extremely difficult. Placental tissue varies widely among species. Thus, experimental animal findings are difficult to apply to humans. Early villous differentiation is difficult to study due to the small tissue size; however, a detailed analysis can potentially elucidate perinatal disease causes or help develop novel therapies. Artificial induction of early villous differentiation using human embryonic stem (ES) cells/induced pluripotent stem (iPS) cells was attempted, producing normally differentiated villi that can be used for interventional/invasive research. Here, we summarized and correlated early villous differentiation findings and discussed clinical diseases.     

Uterine Deletion of Bmal1 Impairs Placental Vascularization and Induces Intrauterine Fetal Death in Mice

Recently, it was demonstrated that the expression of BMAL1 was decreased in the endometrium of women suffering from recurrent spontaneous abortion. To investigate the pathological roles of uterine clock genes during pregnancy, we produced conditional deletion of uterine Bmal1 (cKO) mice and found that cKO mice could receive embryo implantation but not sustain pregnancy. Gene ontology analysis of microarray suggested that uterine NK (uNK) cell function was suppressed in cKO mice. Histological examination revealed the poor formation of maternal vascular spaces in the placenta. In contrast to WT mice, uNK cells in the spongiotrophoblast layer, where maternal uNK cells are directly in contact with fetal trophoblast, hardly expressed an immunosuppressive NK marker, CD161, in cKO mice. By progesterone supplementation, pregnancy could be sustained until the end of pregnancy in some cKO mice. Although this treatment did not improve the structural abnormalities of the placenta, it recruited CD161-positive NK cells into the spongiotrophoblast layer in cKO mice. These findings indicate that the uterine clock system may be critical for pregnancy maintenance after embryo implantation.     

Effect of Non-Equilibrium Condensation of Moist Air on Flow Field in Ludwieg Tube

The time-dependent behavior of non-equilibrium condensation of moist air through a Ludwieg tube with a diaphragm downstream is investigated by using a computational fluid dynamics work. The two-dimensional, compressible, Navier-Stokes equations, fully coupled with the condensate droplet growth equations, are numerically solved by a third-order MUSCL type TVD finite-difference scheme with a second-order fractional time step. Baldwin-Lomax turbulence model is employed to close the governing equations. The present computations represent the experimental flows well. The results obtained show that for an initial relative humidity over 40 %, the periodic excursions of the condensation shock occurs in the Ludwieg tube, and the frequency increases with the initial relative humidity. It is also found that total pressure loss due to non-equilibrium condensation in the Ludwieg tube should not be ignored even for a very low initial relative humidity. Furthermore, the variations of condensation properties are also di     

TAK-603 selectively suppresses Th1-type cytokine production and inhibits the progression of adjuvant arthritis

Lipopeptides carrying a farnesyl thioether or a palmitic acid thioester and a farnesyl thioether were prepared from S-farnesyl cysteine methyl ester by N-terminal extension of the peptide chain employing the base labile Fmoc blocking group of the palladium(0) sensitive Aloc urethane. By means of this technique a lipohexapeptide representing the completely functionalized, i.e. palmitoylated and farnesylated C-terminus of the human N-Ras protein, was prepared. If acid labile blocking functions like the Boc group were used, upon deprotection an undesired addition of the acid to the double bonds of the farnesyl residue occurred. Therefore, acid labile blocking groups should not be employed in the synthesis of farnesylated lipopeptides. The lipopeptide methyl esters which carry only a farnesyl group do not inhibit protein farnesyl transferase, whereas palmitoylated peptides are weak inhibitors of this enzyme.     

Photochemical and thermoelectric utilization of solar energy in a hybrid water-splitting system

A hybrid thermochemical water-splitting cycle using solar energy is proposed and experimental results are presented. The cycle consists of a photochemical reaction conducted in a flat cell with a Fresnel lens and concentrating the remaining solar energy on a thermoelectric generator which produces electric power for the electrolysis steps. The photochemical reaction is:

$\text{2}\text{Fe}{}^{\mathrm{2+}}\text{+}\text{I}{}^{\mathrm{?}}\text{+}\text{light}\text{→2}\text{Fe}{}^{\mathrm{3+}}\text{+3}\text{I}{}^{\mathrm{?}}$

The overall efficiency is estimated to be as high as 15–25%.     

The preparation of copper fine particle paste and its application as the inner electrode material of a multilayered ceramic capacitor

Well size-controlled copper fine particles (diameter: 100-300?nm) were used as the inner electrode material of multilayered ceramic capacitors (MLCCs). The particles were dispersed in terpineol to form a printing paste with 50?wt% copper particles. The MLCC precursor modules prepared by the layer-by-layer printing of copper and BaTiO(3) particles were cosintered. Detailed observation of the particles, paste, and MLCCs before and after sintering was carried out by electron microscopy. The sintering temperature of Cu-MLCC was as low as 960?°C. The permittivity of these MLCCs was successfully measured with the copper inner layers.     

Nano-structural Modification of Amorphous Carbon Thin Films by Low-energy Electron Beam Irradiation

CARBON-BASED MATERIALS have been regardedas one of the most important materials in nano-technology.Not only nanotubes and fullerenes but alsoa new form of carbon incorporating distinct graphiticconfigurations in amorphous carbon networks hasrecently attracted extensive interests in order toaccomplish high performances by combining diversephysical properties which arise from carbon structuresfl,2].In particular,the establishment of functionallyhybridized carbon systems with a thin film f…     

Enzyme-assisted aqueous extraction of shea fat: A rural approach

The use of enzyme-assisted partial hydrolysis as a preextraction treatment in a rural shea fat extraction process to improve upon the extraction rates of the process was explored following an observed possibility in a preliminary investigation. Finely ground shea kernel meal samples were mixed with water in predetermined ratios and heated to inactivate any enzymes present. A crude protease and an enzyme with both hemicellulase and cellulase activities were added and mixed, also in predetermined concentrations. The suspensions were incubated in a waterbath shaker at temperatures ranging from 30 to 45°C for specified periods of time. The treated meal samples were then extracted using an adapted traditional aqueous extraction process. At optimum meal-to-water ratio of 1:2, enzyme concentration of 1%, the natural pH of the meal (about 5.3), and incubation time of 4 h, the enzyme treatment increased the extraction rate from about 40% in the typical traditional system (control) to about 75%, of the total fat content (estimated by the Soxhlet method). The enzyme-treated meal samples were very easy to extract as there was no need to cream or whip out the fat, as is laboriously done in the traditional process. The extracted fat samples had apparently less unsaponifiable matter content and slightly less free fatty acid content and peroxide value, compared to samples from the typical traditional process and, in some cases, the Soxhlet extracted samples. The observations confirmed the results of the preliminary investigations and suggest that the enzyme-assisted preextraction treatment could significantly improve upon the aqueous shea fat extraction process.     

Effects of electrode arrangement and pressure on synthesis of diamond films by arc discharge plasma jet chemical vapor deposition

The setup and deposition conditions of electrode arrangement and pressure have been studied to synthesize diamond films at high growth rate on wide area efficiently by arc discharge plasma jet chemical vapor deposition. An apparatus has been used in which four plasma torches, one is used for cathode and the others for divided anodes, are arranged and the positions of these torches are changeable. Growth rate, deposition area and thickness of diamond films have increased with changing the electrode arrangements without improvement of thickness variation. Maximum growth rate of our apparatus has occurred at the pressure of 6.7 kPa and diamond films that have less variations of quality and surface roughness have been synthesized at lower pressure during deposition. Moreover, a high conversion rate, which is the ratio of carbon atoms that form diamond in supplied methane gas, of 16% has been obtained at the pressure of 6.7 kPa and methane concentration of 2%.