Thioredoxin-1 maintains mechanistic target of rapamycin (mTOR) function during oxidative stress in cardiomyocytes

Thioredoxin 1 (Trx1) is a 12-kDa oxidoreductase that catalyzes thiol-disulfide exchange reactions to reduce proteins with disulfide bonds. As such, Trx1 helps protect the heart against stresses, such as ischemia and pressure overload. Mechanistic target of rapamycin (mTOR) is a serine/threonine kinase that regulates cell growth, metabolism, and survival. We have shown previously that mTOR activity is increased in response to myocardial ischemia-reperfusion injury. However, whether Trx1 interacts with mTOR to preserve heart function remains unknown. Using a substrate-trapping mutant of Trx1 (Trx1C35S), we show here that mTOR is a direct interacting partner of Trx1 in the heart. In response to H2O2 treatment in cardiomyocytes, mTOR exhibited a high molecular weight shift in non-reducing SDS-PAGE in a 2-mercaptoethanol-sensitive manner, suggesting that mTOR is oxidized and forms disulfide bonds with itself or other proteins. The mTOR oxidation was accompanied by reduced phosphorylation of endogenous substrates, such as S6 kinase (S6K) and 4E-binding protein 1 (4E-BP1) in cardiomyocytes. Immune complex kinase assays disclosed that H2O2 treatment diminished mTOR kinase activity, indicating that mTOR is inhibited by oxidation. Of note, Trx1 overexpression attenuated both H2O2-mediated mTOR oxidation and inhibition, whereas Trx1 knockdown increased mTOR oxidation and inhibition. Moreover, Trx1 normalized H2O2-induced down-regulation of metabolic genes and stimulation of cell death, and an mTOR inhibitor abolished Trx1-mediated rescue of gene expression. H2O2-induced oxidation and inhibition of mTOR were attenuated when Cys-1483 of mTOR was mutated to phenylalanine. These results suggest that Trx1 protects cardiomyocytes against stress by reducing mTOR at Cys-1483, thereby preserving the activity of mTOR and inhibiting cell death

The Japan Monkey Centre Primates Brain Imaging Repository of high-resolution postmortem magnetic resonance imaging: the second phase of the archive of digital records

超高磁場MRIで見る霊長類「全脳」神経回路の多様性 --分野横断型の霊長類脳標本画像リポジトリ：ヒト脳と精神・神経疾患の理解を加速する国際研究基盤--. 京都大学プレスリリース. 2023-05-22.A comparison of neuroanatomical features of the brain between humans and our evolutionary relatives, nonhuman primates, is key to understanding the human brain system and the neural basis of mental and neurological disorders. Although most comparative MRI studies of human and nonhuman primate brains have been based on brains of primates that had been used as subjects in experiments, it is essential to investigate various species of nonhuman primates in order to elucidate and interpret the diversity of neuroanatomy features among humans and nonhuman primates. To develop a research platform for this purpose, it is necessary to harmonize the scientific contributions of studies with the standards of animal ethics, animal welfare, and the conservation of brain information for long-term continuation of the field. In previous research, we first developed a gated data-repository of anatomical images obtained using 9.4-T ex vivo MRI of postmortem brain samples from 12 nonhuman primate species, and which are stored at the Japan Monkey Centre. In the present study, as a second phase, we released a collection of T2-weighted images and diffusion tensor images obtained in nine species: white-throated capuchin, Bolivian squirrel monkey, stump-tailed macaque, Tibet monkey, Sykes’ monkey, Assamese macaque, pig-tailed macaque, crested macaque, and chimpanzee. Our image repository should facilitate scientific discoveries in the field of comparative neuroscience. This repository can also promote animal ethics and animal welfare in experiments with nonhuman primate models by optimizing methods for in vivo and ex vivo MRI scanning of brains and supporting veterinary neuroradiological education. In addition, the repository is expected to contribute to conservation, preserving information about the brains of various primates, including endangered species, in a permanent digital form

JASMINE: Near-infrared astrometry and time-series photometry science

The Japan Astrometry Satellite Mission for INfrared Exploration (JASMINE) is a planned M-class science space mission by the Institute of Space and Astronautical Science, the Japan Aerospace Exploration Agency. JASMINE has two main science goals. One is Galactic archaeology with a Galactic Center survey, which aims to reveal the Milky Way’s central core structure and formation history from Gaia-level (∼25 ${\mu}$as) astrometry in the near-infrared (NIR) Hw band (1.0–1.6 ${\mu}$m). The other is an exoplanet survey, which aims to discover transiting Earth-like exoplanets in the habitable zone from NIR time-series photometry of M dwarfs when the Galactic Center is not accessible. We introduce the mission, review many science objectives, and present the instrument concept. JASMINE will be the first dedicated NIR astrometry space mission and provide precise astrometric information on the stars in the Galactic Center, taking advantage of the significantly lower extinction in the NIR. The precise astrometry is obtained by taking many short-exposure images. Hence, the JASMINE Galactic Center survey data will be valuable for studies of exoplanet transits, asteroseismology, variable stars, and microlensing studies, including discovery of (intermediate-mass) black holes. We highlight a swath of such potential science, and also describe synergies with other missions

Seismic Exploration Using Active Sources at Kuchierabujima Volcano, Southwest Japan

Seismic exploration using artificial sources was conducted at Kuchierabujima volcano, southwest Japan in November 2004 by 40 participants from 9 national universities andJapan Meteorological Agency to investigate the subsurface seismic structure. The exploration was the 11th joint experiment under the National Project for Prediction of Volcanic Eruptions. A total of 183 temporal stations equippedwith a 2 Hz vertical component seismometer (including 75 3component seismometers) and a portable data logger were deployed on Kuchierabu Island. Dynamite shots with charges of 10-115 kg were detonated at 19 locations, and seismic signals were successfully recorded. To reveal the P-wave velocity structure, 2955 arrival times of the first motion were picked from the seismograms, and 2187 were classified into ranks A and B. From the record sections and the arrival time data, characteristics reflecting the geological structure were identified. Refracted waves of 5 km/s were observed at stations＞5km from the shot points. Apparent velocities near the shot points depend on the surface geology around the shots. P-wave arrived earlier at stations near the summits. Strongly scattered waves were observed similarly near the summits

DOASによって観測された火山ガス放出量の変動について ～桜島・諏訪之瀬島～

我々は火山からのSO2放出量測定のために，光学的な吸収分光計を用いた試験的な測定機器(DOAS)を新たに開発した。この機器の基本的な動作試験は浅間山や三宅島などの日本の火山で2003年に行われてきた。そして，DOASの特性試験と実際の計測が桜島と諏訪之瀬島(トカラ列島の火山島)で2003年の10月から11月にかけて行われた。桜島では500~1000ton/dayのSO2放出量が記録された。活動が最盛期であった桜島からのSO2放出量の半分以下の計測値であるが，現在の桜島の火山活動の低さから考えると妥当である。また，噴火活動が活発である諏訪之瀬島では初のSO2放出量の測定が行われ，約1000ton/dayのSO2放出量が計測された。桜島最盛期と比べるとSO2放出量は低いが，諏訪之瀬島の噴火規模から考えると妥当な放出量と考えられる。一方で，火口近傍にDOASを運び，SO2 column濃度の時間変動の測定にも成功した。We have produced trial instrument for measurement of SO2 emission using differential optical absorption spectrometer (DOAS). Its performance has been tested at several volcanoes in Japan since 2003. The performance of the DOAS and its practice measurement were executed in Sakurajima and Suwanosejima. The SO2 emissions from Sakurajima and Suwanosejima were measured by the DOAS. Sakurajima emitted 500~1000ton/day due to dormancy of the volcanic activity. The excellent portability of the DOAS enables to estimate the SO2 emission from Suwanosejima at 1000ton/day. In addition, the DOAS enables to monitor temporal variation in the SO2 column concentration in the vicinity of the crater. We carried out measurement of the SO2 column concentration (ppmm) in the plume at Suwanosejima.我々は火山からのSO2放出量測定のために，光学的な吸収分光計を用いた試験的な測定機器(DOAS)を新たに開発した。この機器の基本的な動作試験は浅間山や三宅島などの日本の火山で2003年に行われてきた。そして，DOASの特性試験と実際の計測が桜島と諏訪之瀬島(トカラ列島の火山島)で2003年の10月から11月にかけて行われた。桜島では500~1000ton/dayのSO2放出量が記録された。活動が最盛期であった桜島からのSO2放出量の半分以下の計測値であるが，現在の桜島の火山活動の低さから考えると妥当である。また，噴火活動が活発である諏訪之瀬島では初のSO2放出量の測定が行われ，約1000ton/dayのSO2放出量が計測された。桜島最盛期と比べるとSO2放出量は低いが，諏訪之瀬島の噴火規模から考えると妥当な放出量と考えられる。一方で，火口近傍にDOASを運び，SO2 column濃度の時間変動の測定にも成功した。We have produced trial instrument for measurement of SO2 emission using differential optical absorption spectrometer (DOAS). Its performance has been tested at several volcanoes in Japan since 2003. The performance of the DOAS and its practice measurement were executed in Sakurajima and Suwanosejima. The SO2 emissions from Sakurajima and Suwanosejima were measured by the DOAS. Sakurajima emitted 500~1000ton/day due to dormancy of the volcanic activity. The excellent portability of the DOAS enables to estimate the SO2 emission from Suwanosejima at 1000ton/day. In addition, the DOAS enables to monitor temporal variation in the SO2 column concentration in the vicinity of the crater. We carried out measurement of the SO2 column concentration (ppmm) in the plume at Suwanosejima