Well‐defined,environment‐friendly synthesis of polypeptides based on phosgene‐free transformation of amino acids into urethane derivatives and their applications

In this study, both naturally occurring and artificial amino acids were successfully transformed into the corresponding urethane derivatives using diphenyl carbonate. The urethanes thus prepared could be efficiently cyclized into amino acid N‐carboxyanhydrides (NCAs) without the requirement of phosgene. In addition, the presence of primary amines converted the urethane derivatives into NCAs and initiated the ring‐opening polymerization of the in situ formed NCAs, allowing for the well‐defined synthesis of polypeptides. These polypeptides contained initiating ends functionalized by an amine‐derived residue and propagating ends bearing the reactive amino group. By precise control of the structures of the polypeptides, various polypeptide conjugates such as block copolymers and graft copolymers were successfully synthesized as designed, and their applications in antifouling coatings against proteins, drug delivery systems and biosensors were demonstrated. © 2019 Society of Chemical Industry     

Acetaminophen-Induced Rat Hepatotoxicity Based on M1/M2-Macrophage Polarization,in Possible Relation to Damage-Associated Molecular Patterns and Autophagy

Overdose of acetaminophen (APAP), an antipyretic drug, is an important cause of liver injury. However, the mechanism in the rat model remains undetermined. We analyzed APAP-induced hepatotoxicity using rats based on M1/M2-macrophage functions in relation to damage-associated molecular patterns (DAMPs) and autophagy. Liver samples from six-week-old rats injected with APAP (1000 mg/kg BW, ip, once) after 15 h fasting were collected at hour 10, and on days 1, 2, 3, and 5. Liver lesions consisting of coagulation necrosis and inflammation were seen in the affected centrilobular area on days 1 and 2, and then, recovered with reparative fibrosis by day 5. Liver exudative enzymes increased transiently on day 1. CD68⁺ M1-macrophages increased significantly on days 1 and 2 with increased mRNAs of M1-related cytokines such as IFN-γ and TNF-α, whereas CD163⁺ M2-macrophages appeared later on days 2 and 3. Macrophages reacting to MHC class II and Iba1 showed M1-type polarization, and CD204⁺ macrophages tended to be polarized toward M2-type. At hour 10, interestingly, HMGB1 (representative DAMPs) and its related signals, TLR-9 and MyD88, as well as LC3B⁺ autophagosomes began to increase. Collectively, the pathogenesis of rat APAP hepatotoxicity, which is the first, detailed report for a rat model, might be influenced by macrophage functions of M1 type for tissue injury/inflammation and M2-type for anti-inflammatory/fibrosis; particularly, M1-type may function in relation to DAMPs and autophagy. Understanding the interplayed mechanisms would provide new insight into hepato-pathogenesis and contribute to the possible development of therapeutic strategies.     

Possibility of Japanese Cedar Pollen Causing False Positives in the Deep Mycosis Test

Because Japanese cedar pollen (JCP) contains beta-1,3-d-glucan (BG), there is concern that its lingering presence in the atmosphere, especially during its scattering period, may cause false positives in the factor-G-based Limulus amebocyte lysate (LAL) assay used to test for deep mycosis (i.e., G-test). Hence, we examined whether the LAL assay would react positively with substances contained in JCP by using the G-test to measure JCP particles and extracts. BG was purified from the JCP extract on a BG-specific affinity column, and the percentage extractability was measured using three different BG-specific quantitative methods. The G-test detected 0.4 pg BG in a single JCP particle and 10 fg from a single particle in the extract. The percentage extractability of JCP-derived BG was not significantly different among the three quantitative methods. As the JCP particles should technically have been removed during serum separation, they should be less likely to be a direct false-positive factor. However, given that the LAL-assay-positive substances in the JCP extract were not distinguishable by the three BG-specific quantitative methods, we conclude that they may cause the background to rise. Therefore, in Japan false positives arising from JCP contamination should be considered when testing patients for deep mycosis.     

Mutations Associated with Functional Disorder of Xanthine Oxidoreductase and Hereditary Xanthinuria in Humans

Xanthine oxidoreductase (XOR) catalyzes the conversion of hypoxanthine to xanthine and xanthine to uric acid with concomitant reduction of either NAD⁺ or O₂. The enzyme is a target of drugs to treat hyperuricemia, gout and reactive oxygen-related diseases. Human diseases associated with genetically determined dysfunction of XOR are termed xanthinuria, because of the excretion of xanthine in urine. Xanthinuria is classified into two subtypes, type I and type II. Type I xanthinuria involves XOR deficiency due to genetic defect of XOR, whereas type II xanthinuria involves dual deficiency of XOR and aldehyde oxidase (AO, a molybdoflavo enzyme similar to XOR) due to genetic defect in the molybdenum cofactor sulfurase. Molybdenum cofactor deficiency is associated with triple deficiency of XOR, AO and sulfite oxidase, due to defective synthesis of molybdopterin, which is a precursor of molybdenum cofactor for all three enzymes. The present review focuses on mutation or chemical modification studies of mammalian XOR, as well as on XOR mutations identified in humans, aimed at understanding the reaction mechanism of XOR and the relevance of mutated XORs as models to estimate the possible side effects of clinical application of XOR inhibitors.     

First-Order Phase Transition and Anomalous Hysteresis of Binary Bose Mixtures in an Optical Lattice

We study a first-order phase transition between superfluid and Mott insulator phases in binary Bose mixtures loaded into a hypercubic optical lattice. The system is described by a two-component Bose-Hubbard model. Considering the difference between the two kinds of bosons in the intra-component interaction strength, we discuss the metastability of the system and the hysteresis associated with the first-order superfluid-Mott insulator transition. It is found that the sweeping of hopping amplitude induces a conventional hysteresis-loop behavior. We also find an anomalous hysteresis behavior when the chemical potential is varied. In the anomalous hysteresis, the phase transition occurs in a unidirectional way and a hysteresis loop does not form.     

Symmetric lifting posture recognition of skilled experts with linear discriminant analysis by center-of-pressure velocity

Although it has been well known that novices should train a good lifting posture, there was little way to recognize whether the current posture was good or not based on measured data. The purpose of this paper was to classify the difference between skilled experts working at a freight transport company and unskilled novices without any experience during symmetric lifting by using center-of-pressure (CoP) velocities. All the human subjects performed symmetric lifting experiments with closed eyes; the experiments involved lifting loads (6 and 18 kg) to the upside. Time series data of the CoP position were measured, using a Wii Balance Board, and then, the CoP velocities were calculated. The linear discriminant analysis (LDA) was designed by seven indices which were derived from CoP velocities that reflected the center-of-mass acceleration. The result indicated that the designed LDA discriminated the difference in posture between the two groups with the low error rate (0.100 and 0.017) for classification under 6 and 18 kg. Based on measurement results of CoP trajectories, we inferred that the difference in the CoP velocities between the two groups could be attributed to the difference in the balance ability which means that most skilled experts place their body weight on their rearfeet during symmetric lifting. The LDA classifier designed by CoP velocities was helpful for recognition of the difference between skilled experts and unskilled novices during symmetric lifting. Because the skillful characteristics of experts may be responsible for the lightening of the burden on the waist during lifting, it is considered for the regular check of posture to be helpful for reducing the ratio of occupational low back pain at the workplace.     

Principle and application of ball SAW devices

A thin beam of waves usually diverges due to diffraction, which is a limitation of any device using such waves. However, a surface acoustic wave (SAW) on a sphere with an appropriate aperture does not diverge but is collimated, realizing ultra‐multiple roundtrips along an equator of the sphere. This effect is caused by the balance between diffraction and focusing on a spherical surface, and it enables realization of high‐performance ball SAW sensors. © 2009 Wiley Periodicals, Inc. Electr Eng Jpn, 168(1): 41–51, 2009; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/eej.20817