低分子化合物によるタンパク質代謝の調節に関する研究

筑波大学 (University of Tsukuba)201

Verdet constant dispersion of magnesium fluoride for deep-ultraviolet and vacuum-ultraviolet Faraday rotators

The Verdet constant dispersion in magnesium fluoride (MgF2) crystals was evaluated over a wavelength range of 190–300 nm. The Verdet constant was found to be 38.7 rad/(T·m) at a wavelength of 193 nm. These results were fitted using the diamagnetic dispersion model and the classical Becquerel formula. The fitted results can be used for the designing of suitable Faraday rotators at various wavelengths. These results indicate the possibility of using MgF2 as Faraday rotators not only in deep-ultraviolet regions, but also in vacuum-ultraviolet regions owing to its large bandgap

Effect of erbium concentration on the Verdet constant dispersion of LiY1.0-xErxF4 single crystal

The dispersion of the Verdet constant of LiY1.0-xErxF4 crystals was evaluated from 190 nm to 500 nm for different doping concentrations of Er ions. A 15% doping concentration yielded a high Verdet constant of 54.5 rad/(T·m) at 193 nm. This value can be explained by the contribution of the diamagnetic term associated with LiYF4 and the paramagnetic term of the Er ions. Although the LiYF4 crystal yielded a lower value of −36.6 rad/(T·m) at 193 nm from Er-doped LiYF4, it can be used in the vacuum–ultraviolet region because of its high transmittance at wavelengths longer than 120 nm

Lipid flippase dysfunction as a therapeutic target for endosomal anomalies in Alzheimer's disease

Endosomal anomalies because of vesicular traffic impairment have been indicated as an early pathology of Alzheimer'vertical bar disease (AD). However, the mechanisms and therapeutic targets remain unclear. We previously reported thatbCTF, one of the pathogenic metabolites of APP, interacts with TMEM30A. TMEM30A constitutes a lipid flippase with P4-ATPase and regulates vesicular trafficking through the asymmetric distribution of phospholipids. Therefore, the alteration of lipid flippase activity in AD pathology has got attention. Herein, we showed that the interaction between beta CTF and TMEM30A suppresses the physiological formation and activity of lipid flippase in AD model cells, A7, and App(NLG-F/NLG-F) model mice. Furthermore, the T-RAP peptide derived from the beta CTF binding site of TMEM30A improved endosomal anomalies, which could be a result of the restored lipid flippase activity. Our results provide insights into the mechanisms of vesicular traffic impairment and suggest a therapeutic target for AD

Highly Accurate Chemical Formula Prediction Tool Utilizing High-Resolution Mass Spectra, MS/MS Fragmentation, Heuristic Rules, and Isotope Pattern Matching

Mass spectrometry is commonly applied to qualitatively and quantitatively profile small molecules, such as peptides, metabolites, or lipids. Modern mass spectrometers provide accurate measurements of mass-to-charge ratios of ions, with errors as low as 1 ppm. Even such high mass accuracy, however, is not sufficient to determine the unique chemical formula of each ion, and additional algorithms are necessary. Here we present a universal software tool for predicting chemical formulas from high-resolution mass spectrometry data, developed within the MZmine 2 framework. The tool is based on the use of a combination of heuristic techniques, including MS/MS fragmentation analysis and isotope pattern matching. The performance of the tool was evaluated using a real metabolomic data set obtained with the Orbitrap MS detector. The true formula was correctly determined as the highest-ranking candidate for 79% of the tested compounds. The novel isotope pattern-scoring algorithm outperformed a previously published method in 64% of the tested Orbitrap spectra. The software described in this manuscript is freely available and its source code can be accessed within the MZmine 2 source code repository