<Articles>The Discourse Semantics of Visual Perception and Knowledge(<Semantics and Pragmatics>)

1. Introduction A language can be defined as being comprised of a set of linguistic expressions (e.g. words, phrases, sentences, etc.). Linguistic expressions are sometimes characterized in terms of the form-meaning correspondence. ..

Concentration-dependent Dual Effects of Hydrogen Peroxide on Insulin Signal Transduction in H4IIEC Hepatocytes

BACKGROUND: Oxidative stress induced by the accumulation of reactive oxygen species (ROS) has a causal role in the development of insulin resistance, whereas ROS themselves function as intracellular second messengers that promote insulin signal transduction. ROS can act both positively and negatively on insulin signaling, but the molecular mechanisms controlling these dual actions of ROS are not fully understood. METHODOLOGY/PRINCIPAL FINDINGS: Here, we directly treated H4IIEC hepatocytes with hydrogen peroxide (H2O2), a representative membrane-permeable oxidant and the most abundant ROS in cells, to identify the key factors determining whether ROS impair or enhance intracellular insulin signaling. Treatment with high concentrations of H2O2 (25-50 µM) for 3 h reduced insulin-stimulated Akt phosphorylation, and increased the phosphorylation of both JNK and its substrate c-Jun. In contrast, lower concentrations of H2O2 (5-10 µM) enhanced insulin-stimulated phosphorylation of Akt. Moreover, lower concentrations suppressed PTP1B activity, suggesting that JNK and phosphatases such as PTP1B may play roles in determining the thresholds for the diametrical effects of H2O2 on cellular insulin signaling. Pretreatment with antioxidant N-acetyl-L-cysteine (10 mM) canceled the signal-promoting action of low H2O2 (5 µM), and it canceled out further impairment of insulin of insulin signaling induced by high H₂O₂ (25 µM). CONCLUSIONS/SIGNIFICANCE: Our results demonstrate that depending on its concentration, H2O2 can have the positive or negative effect on insulin signal transduction in H4IIEC hepatocytes, suggesting that the concentration of intracellular ROS may be a major factor in determining whether ROS impair or enhance insulin signaling

Spin chirality and electric polarization in multiferroic compounds RRMn2_2O5_5 (R=R=Ho, Er)

Polarized neutron diffraction experiments have been performed on multiferroic materials $R$Mn$_{2}$O$_{5}$ ($R=$Ho, Er) under electric fields in the ferroelectric commensurate (CM) and the low-temperature incommensurate (LT-ICM) phases, where the former has the highest electric polarization and the latter has reduced polarization. It is found that, after cooling in electric fields down to the CM phase, the magnetic chirality is proportional to the electric polarization. Also we confirmed that the magnetic chirality can be switched by the polarity of the electric polarization in both the CM and LT-ICM phases. These facts suggest an intimate coupling between the magnetic chirality and the electric polarization. However, upon the transition from the CM to LT-ICM phase, the reduction of the electric polarization is not accompanied by any reduction of the magnetic chirality, implying that the CM and LT-ICM phases contain different mechanisms of the magnetoelectric coupling.Comment: 4 pages, 2 figures. Proceedings of PNCMI2008/QuBS200

Structures and mechanisms of actin ATP hydrolysis

The major cytoskeleton protein actin undergoes cyclic transitions between the monomeric G-form and the filamentous F-form, which drive organelle transport and cell motility. This mechanical work is driven by the ATPase activity at the catalytic site in the F-form. For deeper understanding of the actin cellular functions, the reaction mechanism must be elucidated. Here, we show that a single actin molecule is trapped in the F-form by fragmin domain-1 binding and present their crystal structures in the ATP analog-, ADP-Pi-, and ADP-bound forms, at 1.15-Å resolutions. The G-to-F conformational transition shifts the side chains of Gln137 and His161, which relocate four water molecules including W1 (attacking water) and W2 (helping water) to facilitate the hydrolysis. By applying quantum mechanics/molecular mechanics calculations to the structures, we have revealed a consistent and comprehensive reaction path of ATP hydrolysis by the F-form actin. The reaction path consists of four steps: 1) W1 and W2 rotations; 2) PG–O3B bond cleavage; 3) four concomitant events: W1–PO3− formation, OH− and proton cleavage, nucleophilic attack by the OH− against PG, and the abstracted proton transfer; and 4) proton relocation that stabilizes the ADP-Pi–bound F-form actin. The mechanism explains the slow rate of ATP hydrolysis by actin and the irreversibility of the hydrolysis reaction. While the catalytic strategy of actin ATP hydrolysis is essentially the same as those of motor proteins like myosin, the process after the hydrolysis is distinct and discussed in terms of Pi release, F-form destabilization, and global conformational changes

構造研究に基づく南海トラフ（西部）地震発生帯のプレート形状および速度構造の3次元モデル

Great interplate earthquakes have repeatedly occurred in pairs along the Nankai Trough. In order to reduce a great deal of damage to coastal area from both strong ground motion and tsunami generation, it is necessary to understand rupture synchronization and segmentation of the Nankai megathrust earthquake. For a precise estimate of the rupture zone of the Nankai megathrust event based on the knowledge of realistic earthquake cycles and variations of magnitude, it is important to know the geometry and property of the plate boundary of the subduction seismogenic zone. To improve a physical model of the Nankai Trough seismogenic zone, the large-scale high-resolution wide-angle and reflection (MCS) seismic studies, and long-term observation have been conducted since 2008. Marine active source seismic data have been acquired along grid two-dimensional profiles having the total length of ~800km per year. A three-dimensional seismic tomography using active and passive seismic data observed both land and ocean bottom stations have been also performed. This study is part of 'Research concerning Interaction Between the Tokai, Tonankai and Nankai Earthquakes' funded by Ministry of Education, Culture, Sports, Science and Technology, Japan. The seismic survey was conducted off the Tokai area including the onshore survey across the eastern Kii Peninsula in 2012, the final year of this project. Compiling those studies provides a three-dimensional plate geometry and velocity structure models of the western Nankai Trough at the moment. Although their reliability and resolution should be evaluated, these models can be applied to a numerical simulation to examine if the observed rupture zone of the historical event can be reproduced. We will also try to construct more fine-scale model for the entire Nankai Trough area.SSS31-P15ポスター要旨 / 日本地球惑星科学連合2013年大会（2013年5月19日～5月24日, 幕張メッセ国際会議場） / 日本惑星科学連合の許諾に基づき本文ファイルを掲載http://www.godac.jamstec.go.jp/darwin/cruise/kairei/kr10-11/ehttp://www.godac.jamstec.go.jp/darwin/cruise/kairei/kr11-09/

Development of the photomultiplier tube readout system for the first Large-Sized Telescope of the Cherenkov Telescope Array

The Cherenkov Telescope Array (CTA) is the next generation ground-based very high energy gamma-ray observatory. The Large-Sized Telescope (LST) of CTA targets 20 GeV -- 1 TeV gamma rays and has 1855 photomultiplier tubes (PMTs) installed in the focal plane camera. With the 23 m mirror dish, the night sky background (NSB) rate amounts to several hundreds MHz per pixel. In order to record clean images of gamma-ray showers with minimal NSB contamination, a fast sampling of the signal waveform is required so that the signal integration time can be as short as the Cherenkov light flash duration (a few ns). We have developed a readout board which samples waveforms of seven PMTs per board at a GHz rate. Since a GHz FADC has a high power consumption, leading to large heat dissipation, we adopted the analog memory ASIC "DRS4". The sampler has 1024 capacitors per channel and can sample the waveform at a GHz rate. Four channels of a chip are cascaded to obtain deeper sampling depth with 4096 capacitors. After a trigger is generated in a mezzanine on the board, the waveform stored in the capacitor array is subsequently digitized with a low speed (33 MHz) ADC and transferred via the FPGA-based Gigabit Ethernet to a data acquisition system. Both a low power consumption (2.64 W per channel) and high speed sampling with a bandwidth of $>$300 MHz have been achieved. In addition, in order to increase the dynamic range of the readout we adopted a two gain system achieving from 0.2 up to 2000 photoelectrons in total. We finalized the board design for the first LST and proceeded to mass production. Performance of produced boards are being checked with a series of quality control (QC) tests. We report the readout board specifications and QC results.Comment: In Proceedings of the 34th International Cosmic Ray Conference (ICRC2015), The Hague, The Netherlands. All CTA contributions at arXiv:1508.0589

Spiral Spin Structures and Origin of the Magnetoelectric Coupling in YMn\u3csub\u3e2\u3c/sub\u3eO\u3csub\u3e5\u3c/sub\u3e

By combining neutron four-circle diffraction and polarized neutron-diffraction techniques we have determined the complex spin structures of a multiferroic YMn2O5 that exhibits two ferroelectric phases at low temperatures. The obtained magnetic structure has spiral components in both the low-temperature ferroelectric phases that are magnetically commensurate and incommensurate, respectively. Among proposed microscopic theories for the magnetoelectric coupling, our results are consistent with both the spin-current mechanism and the magnetostriction mechanism. Our results also explain why the electric polarization changes at the low-temperature commensurate-to-incommensurate phase transition

Pharmacokinetics of (-)Epicatechin 3-O-Gallate, Glycyrrhetic Acid and Rhein in Healthy Male Volunteers after a Single Dose Administration of TJ-8117 (Unpito), a Japanese Traditional Medicine for Renal Failure

Aims: Unpito, an herbal medicine extracted from a mixture of five crude medicines (Rhei Rhizoma, Glycyrrhizae Radix, Ginseng Radix, Zingiberis Rhizoma and Aconiti Tuber), has been developed as a drug for chronic renal failure. In general, it is difficult to estimate the absorption and excretion of herbal medicines due to the presence of a wide variety of components. The purpose of the current study was to examine the systemic pharmacokinetics and elimination of Unpito in healthy volunteers as part of the clinical study of the medicine. Methods: Three compounds, (-)epicatechin 3-O-gallate (ECG), glycyrrhetic acid (GA) and rhein (RH) were selected as markers, to examine the clinical pharmacokinetics of Unpito based on their levels in this medicine. The disposition of each compound was evaluated in 32 healthy volunteers receiving single oral doses (2, 4, 8, and 12 capsules). Results: After a single oral administration, ECG and RH exhibited linear pharmacokinetics in AUC and C max, while GA did not exhibit linear pharmacokinetics. A cross-over study was conducted to evaluate the effect of food at a single dose of 4 capsules. The effect of food was observed for the plasma concentrations of ECG and RH, while not for GA. The potential accumulations of δ-(3,4- dihydroxyphenyl)-γ-valerolactone (VL-2), a metabolite of ECG and RH were not observed. GA was not detected in urine. Conclusions: This is the first study presenting pharmacokinetics of ECG, GA and RH derived from Unpito, an herbal medicine, in healthy volunteers after single dose administration.出版者照会後に全文公

Regulation of NR4A nuclear receptors by p38

In Drosophila, the melanization reaction is an important defense mechanism against injury and invasion of microorganisms. Drosophila tyrosine hydroxylase (TH, also known as Pale) and dopa decarboxylase (Ddc), key enzymes in the dopamine synthesis pathway, underlie the melanin synthesis by providing the melanin precursors dopa and dopamine, respectively. It has been shown that expression of Drosophila TH and Ddc is induced in various physiological and pathological conditions, including bacterial challenge; however, the mechanism involved has not been fully elucidated. Here, we show that ectopic activation of p38 MAPK induces TH and Ddc expression, leading to upregulation of melanization in the Drosophila cuticle. This p38-dependent melanization was attenuated by knockdown of TH and Ddc, as well as by that of Drosophila HR38, a member of the NR4A family of nuclear receptors. In mammalian cells, p38 phosphorylated mammalian NR4As and Drosophila HR38 and potentiated these NR4As to transactivate a promoter containing NR4A-binding elements, with this transactivation being, at least in part, dependent on the phosphorylation. This suggests an evolutionarily conserved role for p38 MAPKs in the regulation of NR4As. Thus, p38-regulated gene induction through NR4As appears to function in the dopamine synthesis pathway and may be involved in immune and stress responses