421 results on '"Uesaka M"'
Search Results
202. Plasma wakefield acceleration experiments in overdense regime driven by narrow bunches.
- Author
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Kozawa, T., Ueda, T., Kobayashi, T., Uesaka, M., Miya, K., Ogata, A., Nakanishi, H., Kawakubo, T., Arinaga, M., Nakajima, K., Shibata, H., Yugami, N., Nishida, Y., Whittum, D., and Yoshida, Y.
- Published
- 1995
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203. Single-crystal growth of Pb2V3O9 and the Bose-Einstein condensed state of triplons studied by thermal conductivity, specific heat and magnetization measurements.
- Author
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Kawamata, T., Sugawara, N., Uesaka, M., Kaneko, N., Kajiwara, T., Yamane, H., Koyama, K., Kudo, K., Kobayashi, N., and Koike, Y.
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- 2009
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204. Characteristics of pico-second single bunch at the S-band linear accelerator
- Author
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Uesaka, M., Kozawa, T., Kobayashi, T., and Ueda, T.
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- 1994
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205. Substrate stereoselectivity and enantiomer/enantiomer interaction in propranolol metabolism in rat liver microsomes
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Masubuchi, Y., Yamamoto, L. Aquira, Uesaka, M., and Fujita, S.
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- 1993
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206. Nondestructive beam position monitor using high-permeability chips
- Author
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Kobayashi, T., Kozawa, T., Ueda, T., and Uesaka, M.
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- 1995
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207. EMITTANCE AND ENERGY MEASUREMENTS OF LOW-ENERGY ELECTRON BEAM USING OPTICAL TRANSITION RADIATION TECHNIQUES
- Author
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UESAKA, M
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- 2005
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208. Application of Laser Plasma X-rays to Time-resolved Debye-Sherrer Diffraction
- Author
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Uesaka, M [Nuclear Engineering Research Laboratory, University of Tokyo, 2-22 Shirakata-Sirane, Toukai-mura, Naka-gun, Ibaraki-ken, 319-1188 (Japan)]
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- 2003
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209. Fundamental Study for Time-Resolved Imaging by Laser Plasma X-rays
- Author
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Uesaka, M [Nuclear Engineering Research Laboratory, University of Tokyo, 2-22 Shirakata-Shirane, Tokai-mura, Naka-gun, Ibaraki-ken, 319-1188 (Japan)]
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- 2003
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210. CdTe Detectors
- Author
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Leonardo ABBENE, Stefano DEL SORDO, Uesaka M, Danielsson M, Abbene, L, and Del Sordo, S
- Subjects
Materials science ,Physics::Instrumentation and Detectors ,Condensed Matter::Other ,business.industry ,Physics::Medical Physics ,Detector ,Settore FIS/01 - Fisica Sperimentale ,Cdte detector ,Cadmium telluride photovoltaics ,Settore FIS/07 - Fisica Applicata(Beni Culturali, Ambientali, Biol.e Medicin) ,Semiconductor detector ,Condensed Matter::Materials Science ,Optoelectronics ,Compound semiconductor ,High Energy Physics::Experiment ,business ,Spectroscopy ,CdTe, semiconductor detectors, X-ray spectroscopy, digital pulse processing, medical applications - Abstract
Cadmium telluride (CdTe) compound semiconductors for x-ray detectors have experienced a rather rapid development in the last few years, due to their appealing performance. In this chapter we review the physical properties of semiconductor detectors for x-ray and γ ray spectroscopy. In particular, we focus on compound semiconductor detectors. We also review the principles of operation of both the semiconductor detectors and the electronic chains, with special emphasis on the digital techniques. CdTe detectors’ characteristics and performance enhancements are discussed in depth. Finally, we present some original results on CdTe detectors for medical applications. more...
- Published
- 2014
211. Genomic screening of fish-specific genes in gnathostomes and their functions in fin development.
- Author
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Kudoh H, Yonei-Tamura S, Abe G, Iwakiri J, Uesaka M, Makino T, and Tamura K
- Subjects
- Animals, Genomics, Animal Fins physiology, Zebrafish genetics, Zebrafish Proteins genetics
- Abstract
In this study, we comprehensively searched for fish-specific genes in gnathostomes that contribute to development of the fin, a fish-specific trait. Many previous reports suggested that animal group-specific genes are often important for group-specific traits. Clarifying the roles of fish-specific genes in fin development of gnathostomes, for example, can help elucidate the mechanisms underlying the formation of this trait. We first identified 91 fish-specific genes in gnathostomes by comparing the gene repertoire in 16 fish and 35 tetrapod species. RNA-seq analysis narrowed down the 91 candidates to 33 genes that were expressed in the developing pectoral fin. We analyzed the functions of approximately half of the candidate genes by loss-of-function analysis in zebrafish. We found that some of the fish-specific and fin development-related genes, including fgf24 and and1/and2, play roles in fin development. In particular, the newly identified fish-specific gene qkia is expressed in the developing fin muscle and contributes to muscle morphogenesis in the pectoral fin as well as body trunk. These results indicate that the strategy of identifying animal group-specific genes is functional and useful. The methods applied here could be used in future studies to identify trait-associated genes in other animal groups., (© 2024 The Authors. Development, Growth & Differentiation published by John Wiley & Sons Australia, Ltd on behalf of Japanese Society of Developmental Biologists.) more...
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- 2024
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212. Hagfish genome elucidates vertebrate whole-genome duplication events and their evolutionary consequences.
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Yu D, Ren Y, Uesaka M, Beavan AJS, Muffato M, Shen J, Li Y, Sato I, Wan W, Clark JW, Keating JN, Carlisle EM, Dearden RP, Giles S, Randle E, Sansom RS, Feuda R, Fleming JF, Sugahara F, Cummins C, Patricio M, Akanni W, D'Aniello S, Bertolucci C, Irie N, Alev C, Sheng G, de Mendoza A, Maeso I, Irimia M, Fromm B, Peterson KJ, Das S, Hirano M, Rast JP, Cooper MD, Paps J, Pisani D, Kuratani S, Martin FJ, Wang W, Donoghue PCJ, Zhang YE, and Pascual-Anaya J more...
- Subjects
- Animals, Phylogeny, Gene Duplication, Vertebrates genetics, Genome, Lampreys genetics, Hagfishes genetics
- Abstract
Polyploidy or whole-genome duplication (WGD) is a major event that drastically reshapes genome architecture and is often assumed to be causally associated with organismal innovations and radiations. The 2R hypothesis suggests that two WGD events (1R and 2R) occurred during early vertebrate evolution. However, the timing of the 2R event relative to the divergence of gnathostomes (jawed vertebrates) and cyclostomes (jawless hagfishes and lampreys) is unresolved and whether these WGD events underlie vertebrate phenotypic diversification remains elusive. Here we present the genome of the inshore hagfish, Eptatretus burgeri. Through comparative analysis with lamprey and gnathostome genomes, we reconstruct the early events in cyclostome genome evolution, leveraging insights into the ancestral vertebrate genome. Genome-wide synteny and phylogenetic analyses support a scenario in which 1R occurred in the vertebrate stem-lineage during the early Cambrian, and 2R occurred in the gnathostome stem-lineage, maximally in the late Cambrian-earliest Ordovician, after its divergence from cyclostomes. We find that the genome of stem-cyclostomes experienced an additional independent genome triplication. Functional genomic and morphospace analyses demonstrate that WGD events generally contribute to developmental evolution with similar changes in the regulatory genome of both vertebrate groups. However, appreciable morphological diversification occurred only in the gnathostome but not in the cyclostome lineage, calling into question the general expectation that WGDs lead to leaps of bodyplan complexity., (© 2024. The Author(s).) more...
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- 2024
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213. Estimation of microplastic emission and transfer into Tokyo Bay, Japan, using material flow analysis.
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Ono K, Naito W, Ogura I, Xue M, Kato E, Uesaka M, and Tsunemi K
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- Japan, Tokyo, Bays, Microplastics, Plastics
- Abstract
To reduce microplastic (MP) discharge into the aquatic environment, it is necessary to properly identify its sources and amounts. Here, specific MP sources, i.e., personal care products (PCPs), fibers from clothes, and tire-wear particles (TWPs) were focused, and MP generations from these sources in the Tokyo Bay watershed, Japan, were estimated based on statistical data on production and reported emission factors of the MP sources and executing considering uncertainty on the data. Potential annual MP emission into Tokyo Bay was estimated to be 10.2 ± 1.6, 38 ± 22, and 1500-1800 tons for PCPs, fibers, and TWPs, respectively. Emissions into Tokyo Bay by assuming MP density and diameter was estimated. For fiber, the fraction to potential emission was estimated at 1.0-2.8 %. This study contributes to determining potential discharge pathways. This will assist in the application of appropriate measures to reduce MP discharge into water bodies., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.) more...
- Published
- 2023
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214. A quantitative description of the compatibility of technetium-selective chromatographic technetium-99m separation with low specific activity molybdenum-99.
- Author
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Jang J, Sekimoto S, Ohtsuki T, Tatenuma K, Tsuguchi A, and Uesaka M
- Subjects
- Molybdenum chemistry, Electrons, Technetium chemistry, Radioisotopes
- Abstract
Technetium-99m generators employing a technetium-selective stationary phase are a chromatographic instrument developed for use with
99 Mo having low specific activity (LSA); particularly,99 Mo produced by electron accelerators. This paper presents a mathematical description of technetium-selective chromatographic (TSC)99m Tc separation and analyzes its compatibility with LSA99 Mo. We developed a theoretical formula for TSC99m Tc separation by discretizing its pertechnetate selectivity, and validated it using an electron linear accelerator and activated carbon-based TSC (AC-TSC)99m Tc generators. We confirmed that the activity concentration of99m Tc obtained from a TSC99m Tc generator can be calculated directly from its input99 Mo activity regardless of the99 Mo specific activity. The formula corroborates that TSC99m Tc separation is compatible with LSA99 Mo, and has a practical application in estimating the number of TSC99m Tc generators required for99m Tc demand of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.) more...- Published
- 2023
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215. Design of an Ante-enhancer with an Azone-Mimic Structure using Ionic Liquid.
- Author
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Oshizaka T, Hayakawa M, Uesaka M, Yoshizawa K, Kamei T, Takeuchi I, Mori K, Itakura S, Todo H, and Sugibayashi K
- Subjects
- Animals, Swine, Skin metabolism, Azepines metabolism, Azepines pharmacology, Administration, Cutaneous, Skin Absorption, Ionic Liquids
- Abstract
Purpose: Laurocapram (Azone) was broadly examined as a representative enhancer of skin penetration in the 1980s. However, it was not approved for treatment because it caused skin irritation following its penetration into the epidermis through the stratum corneum. In the present study, a so-called ante-enhancer with an Azone-mimic structure was designed based on an ante-drug with negligible systemic toxic effects following its permeation through the skin., Methods: The ante-enhancer was designed using ionic liquid technology: an ionic liquid-type ante-enhancer (IL-Azone) with an Azone-mimic structure was prepared from ε-caprolactam and myristic acid as cationic and anionic substances, respectively. The enhancing effects of IL-Azone on the permeation by the following model drugs through pig skin were examined: isosorbide 5-mononitrate (ISMN), antipyrine (ANP), and fluorescein isothiocyanate dextran (FD-4). Skin irritation by IL-Azone was assessed using the Draize method., Results: The primary irritation index (P.I.I.) of IL-Azone by the Draize method was markedly lower than that of Azone (6.9). Although the ability of IL-Azone to enhance skin penetration was not as high as Azone, IL-Azone moderately increased skin permeation by the model compounds tested (ISMN: 4.7 fold, ANP: 4.5 fold, FD-4: 4.0 fold)., Conclusions: These results suggest the usefulness of designing a skin penetration enhancer using ionic liquid technology. Further trials on the ionic liquid design with an Azone-mimic structure using other cations and anions may lead to the development of better ante-enhancers., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.) more...
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- 2023
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216. YAP/TAZ-TEAD is a novel transcriptional regulator of genes encoding steroidogenic enzymes in rat granulosa cells and KGN cells.
- Author
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Mizutani T, Orisaka M, Kawabe S, Morichika R, Uesaka M, and Yoshida Y
- Subjects
- Female, Rats, Animals, Granulosa Cells metabolism, Gene Expression Regulation, Follicle Stimulating Hormone metabolism, Transcription Factors genetics, Transcription Factors metabolism, YAP-Signaling Proteins
- Abstract
Steroidogenesis in ovarian granulosa cells is regulated by the follicle-stimulating hormone (FSH) via transcriptional regulation of its related genes. We herein showed the involvement of the Hippo pathway in this regulation. In KGN granulosa cell, repression of YAP/TAZ activity induced the expression of CYP11A1, HSD3B2, and CYP19A1 in a TEAD-dependent manner without cAMP stimulation. A selective inhibitor of p38 MAP kinase, suppressed YAP/TAZ knockdown-indued the expression of these genes, suggesting this signal could be involved. The expression of these genes was induced by 8Br-cAMP, whereas that of CYR61 and ADATS1, typical YAP/TAZ-TEAD target genes, was suppressed, suggesting that the cellular signaling of cAMP reduced YAP/TAZ-TEAD activity. The constitutively active mutant YAP canceled the FSH- and 8Br-cAMP-mediated induction of these genes in primary rat granulosa and KGN cells, respectively. Moreover, regulation of steroidogenesis-related genes by YAP/TAZ-TEAD was independent of steroidogenic factor 1, a master gene regulator of steroidogenesis. These results suggest that YAP/TAZ-TEAD is a negative regulator of steroidogenesis and that suppression of YAP/TAZ-TEAD activity by FSH is involved in ovarian steroidogenesis., Competing Interests: Declaration of competing interest The authors have nothing to disclose., (Copyright © 2022 Elsevier B.V. All rights reserved.) more...
- Published
- 2023
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217. Laser-driven multi-MeV high-purity proton acceleration via anisotropic ambipolar expansion of micron-scale hydrogen clusters.
- Author
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Jinno S, Kanasaki M, Asai T, Matsui R, Pirozhkov AS, Ogura K, Sagisaka A, Miyasaka Y, Nakanii N, Kando M, Kitagawa N, Morishima K, Kodaira S, Kishimoto Y, Yamauchi T, Uesaka M, Kiriyama H, and Fukuda Y more...
- Abstract
Multi-MeV high-purity proton acceleration by using a hydrogen cluster target irradiated with repetitive, relativistic intensity laser pulses has been demonstrated. Statistical analysis of hundreds of data sets highlights the existence of markedly high energy protons produced from the laser-irradiated clusters with micron-scale diameters. The spatial distribution of the accelerated protons is found to be anisotropic, where the higher energy protons are preferentially accelerated along the laser propagation direction due to the relativistic effect. These features are supported by three-dimensional (3D) particle-in-cell (PIC) simulations, which show that directional, higher energy protons are generated via the anisotropic ambipolar expansion of the micron-scale clusters. The number of protons accelerating along the laser propagation direction is found to be as high as 1.6 [Formula: see text] [Formula: see text] 10[Formula: see text]/MeV/sr/shot with an energy of 2.8 [Formula: see text] MeV, indicating that laser-driven proton acceleration using the micron-scale hydrogen clusters is promising as a compact, repetitive, multi-MeV high-purity proton source for various applications., (© 2022. The Author(s).) more...
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- 2022
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218. Inhibition of YAP/TAZ-TEAD activity induces cytotrophoblast differentiation into syncytiotrophoblast in human trophoblast.
- Author
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Mizutani T, Orisaka M, Miyazaki Y, Morichika R, Uesaka M, Miyamoto K, and Yoshida Y
- Subjects
- Female, Humans, Placenta metabolism, Pregnancy, Transcription Factors genetics, Transcription Factors metabolism, YAP-Signaling Proteins, Adaptor Proteins, Signal Transducing genetics, Adaptor Proteins, Signal Transducing metabolism, Trophoblasts metabolism
- Abstract
During placentation, placental cytotrophoblast (CT) cells differentiate into syncytiotrophoblast (ST) cells and extravillous trophoblast (EVT) cells. In the placenta, the expression of various genes is regulated by the Hippo pathway through a transcription complex, Yes-associated protein (YAP)/transcriptional coactivator with PDZ-binding motif (TAZ)-TEA domain transcription factor (TEAD) (YAP/TAZ-TEAD) activity. YAP/TAZ-TEAD activity is controlled by multiple factors and signaling, such as cAMP signaling. cAMP signaling is believed to be involved in the regulation of trophoblast function but is not yet fully understood. Here we showed that YAP/TAZ-TEAD expressions and their activities were altered by cAMP stimulation in BeWo cells, a human choriocarcinoma cell line. The repression of YAP/TAZ-TEAD activity induced the expression of ST-specific genes without cAMP stimulation, and transduction of constitutively active YAP, i.e. YAP-5SA, resulted in the repression of 8Br-cAMP-induced expressions of ST-specific genes in a TEAD-dependent manner. We also investigated the role of YAP/TAZ-TEAD in maintaining CT cells and their differentiation into ST and EVT cells using human trophoblast stem (TS) cells. YAP/TAZ-TEAD activity was involved in maintaining the stemness of TS cells. Induction or repression of YAP/TAZ-TEAD activity resulted in marked changes in the expression of ST-specific genes. Using primary CT cells, which spontaneously differentiate into ST-like cells, the effects of YAP-5SA transduction were investigated, and the expression of ST-specific genes was found to be repressed. These results indicate that the inhibition of YAP/TAZ-TEAD activity, with or without cAMP stimulation, is essential for the differentiation of CT cells into ST cells., (© The Author(s) 2022. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please email: journals.permissions@oup.com.) more...
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- 2022
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219. A preliminary biodistribution study of [ 99m Tc]sodium pertechnetate prepared from an electron linear accelerator and activated carbon-based 99m Tc generator.
- Author
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Jang J, Kumakura Y, Tatenuma K, Ozeki AN, Wada Y, Akimitsu N, Tsuguchi A, Kikunaga H, Higaki S, and Uesaka M
- Subjects
- Animals, Electrons, Female, Mice, Mice, Inbred ICR, Particle Accelerators, Sodium, Tissue Distribution, Charcoal, Sodium Pertechnetate Tc 99m
- Abstract
Introduction: Production of
99 Mo/99m Tc using an electron linear accelerator (linac) and activated carbon (AC)-based99mript> Tc generator (linac-AC) is an alternative approach to the conventional fission production of 99 Mo/99m Tc. As a preliminary investigation of the clinical applicability of a linac-AC-derived99m Tc radiopharmaceutical, the biodistribution of linac-AC-derived [99m Tc]sodium pertechnetate ([99m Tc]NaTcO4 ) was measured and compared against fission-derived [99m Tc]NaTcO4 at one time point., Methods:99 Mo was produced by irradiating nonenriched MoO3 targets with bremsstrahlung photons generated from 55.5-MeV linac electron beams.99m Tc was then separated and purified from the99 Mo using an AC-based99m Tc generator. Subsequently, biodistribution of the linac-AC-derived [99m Tc]NaTcO4 in healthy female Slc:ICR mice (n = 6) was measured by dissection and compared with that of fission-derived [99m Tc]NaTcO4 (n = 4) at 30 min after injection., Results: The two types of [99m Tc]NaTcO4 exhibited similar biodistribution in all the organs and tissues examined: the uptakes of [99m Tc]NaTcO4 prepared from the linac-AC method and those prepared from the fission method were 138.9 ± 69.9%ID/g and 160.6 ± 49.2%ID/g in the thyroids, respectively, 33.4 ± 5.5%ID/g and 29.4 ± 9.1%ID/g in the salivary glands, respectively, and less than 10%ID/g in blood and all the other organs. No adverse effects were observed in the mice administered with either [99m Tc]NaTcO4 ., Conclusion: The clinical applicability of linac-AC-derived [99m Tc]NaTcO4 was suggested by its similar biodistribution with fission-derived [99m Tc]NaTcO4 at one time point. Further biodistribution studies at multiple time points are encouraged to demonstrate the bioequivalence between linac-AC- and fission-derived [99m Tc]NaTcO4 ., (Copyright © 2022 Elsevier Inc. All rights reserved.) more...- Published
- 2022
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220. Prediction of the position of external markers using a recurrent neural network trained with unbiased online recurrent optimization for safe lung cancer radiotherapy.
- Author
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Pohl M, Uesaka M, Takahashi H, Demachi K, and Bhusal Chhatkuli R
- Subjects
- Algorithms, Humans, Lung, Motion, Respiration, Lung Neoplasms radiotherapy, Neural Networks, Computer
- Abstract
Background and Objective: During lung cancer radiotherapy, the position of infrared reflective objects on the chest can be recorded to estimate the tumor location. However, radiotherapy systems have a latency inherent to robot control limitations that impedes the radiation delivery precision. Prediction with online learning of recurrent neural networks (RNN) allows for adaptation to non-stationary respiratory signals, but classical methods such as real-time recurrent learning (RTRL) and truncated backpropagation through time are respectively slow and biased. This study investigates the capabilities of unbiased online recurrent optimization (UORO) to forecast respiratory motion and enhance safety in lung radiotherapy., Methods: We used nine observation records of the three-dimensional (3D) position of three external markers on the chest and abdomen of healthy individuals breathing during intervals from 73s to 222s. The sampling frequency was 10Hz, and the amplitudes of the recorded trajectories range from 6mm to 40mm in the superior-inferior direction. We forecast the 3D location of each marker simultaneously with a horizon value (the time interval in advance for which the prediction is made) between 0.1s and 2.0s, using an RNN trained with UORO. We compare its performance with an RNN trained with RTRL, least mean squares (LMS), and offline linear regression. We provide closed-form expressions for quantities involved in the gradient loss calculation in UORO, thereby making its implementation efficient. Training and cross-validation were performed during the first minute of each sequence., Results: On average over the horizon values considered and the nine sequences, UORO achieves the lowest root-mean-square (RMS) error and maximum error among the compared algorithms. These errors are respectively equal to 1.3mm and 8.8mm, and the prediction time per time step was lower than 2.8ms (Dell Intel core i9-9900K 3.60 GHz). Linear regression has the lowest RMS error for the horizon values 0.1s and 0.2s, followed by LMS for horizon values between 0.3s and 0.5s, and UORO for horizon values greater than 0.6s., Conclusions: UORO can accurately predict the 3D position of external markers for intermediate to high response times with an acceptable time performance. This will help limit unwanted damage to healthy tissues caused by radiotherapy., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest., (Copyright © 2022. Published by Elsevier B.V.) more...
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- 2022
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221. Distinguishing Evolutionary Conservation from Derivedness.
- Author
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Leong JCK, Uesaka M, and Irie N
- Abstract
While the concept of "evolutionary conservation" has enabled biologists to explain many ancestral features and traits, it has also frequently been misused to evaluate the degree of changes from a common ancestor, or "derivedness". We propose that the distinction of these two concepts allows us to properly understand phenotypic and organismal evolution. From a methodological aspect, "conservation" mainly considers genes or traits which species have in common, while "derivedness" additionally covers those that are not commonly shared, such as novel or lost traits and genes to evaluate changes from the time of divergence from a common ancestor. Due to these differences, while conservation-oriented methods are effective in identifying ancestral features, they may be prone to underestimating the overall changes accumulated during the evolution of certain lineages. Herein, we describe our recently developed method, "transcriptomic derivedness index", for estimating the phenotypic derivedness of embryos with a molecular approach using the whole-embryonic transcriptome as a phenotype. Although echinoderms are often considered as highly derived species, our analyses with this method showed that their embryos, at least at the transcriptomic level, may not be much more derived than those of chordates. We anticipate that the future development of derivedness-oriented methods could provide quantitative indicators for finding highly/lowly evolvable traits. more...
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- 2022
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222. Beyond recapitulation: Past, present, and future.
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Uesaka M and Irie N
- Published
- 2022
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223. How can recapitulation be reconciled with modern concepts of evolution?
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Kuratani S, Uesaka M, and Irie N
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- Animals, Phylogeny, Biological Evolution
- Abstract
To understand Haeckel's idea of recapitulation with modern evolutionary biology, one has to realize how evolutionarily conserved embryonic stages appear sequentially in developmental processes as chains of causality. Whether the idea of evolution was accepted or not, Haeckel and von Baer commonly saw an importance of a particularly conserved mid-embryonic stage in biphasic development of metazoans, the phylotype, that defines an animal phylum as the developmental source of a basic body plan. In an evolutionary context, the phylotypic stage was once understood by Haeckel to reflect the common ancestor of animal phyla, which went through hypermorphosis independently into various phyla. Recent comprehensive molecular studies, however, accumulated data to refute this idea. The conserved embryonic pattern does not reflect an ancestral adult morphology but appears to have arisen primarily as an embodiment of developmental constraints established through evolutionary processes. How the developmental burden results in a nested series of constraints will solve the recapitulative tendency of developmental programs., (© 2020 Wiley Periodicals LLC.) more...
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- 2022
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224. In the Spotlight-Postdoc.
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Uesaka M
- Subjects
- Animals, Humans, Research Personnel
- Published
- 2022
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225. The developmental hourglass model and recapitulation: An attempt to integrate the two models.
- Author
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Uesaka M, Kuratani S, and Irie N
- Subjects
- Animals, Biological Evolution, Phylogeny, Transcriptome, Embryonic Development genetics, Gene Expression Regulation, Developmental
- Abstract
Recapitulation is a hypothetical concept that assumes embryogenesis of an animal parallels its own phylogenetic history, sequentially developing from more ancestral features to more derived ones. This concept predicts that the earliest developmental stage of various animals should represent the most evolutionarily conserved patterns. Recent transcriptome-based studies, on the other hand, have reported that mid-embryonic, organogenetic periods show the highest level of conservation (the developmental hourglass model). This, however, does not rule out the possibility that recapitulation would still be detected after the mid-embryonic period. In accordance with this, recapitulation-like morphological features are enriched in late developmental stages. Moreover, our recent chromatin accessibility-based study provided molecular evidence for recapitulation in the mid-to-late embryogenesis of vertebrates, as newly evolved gene regulatory elements tended to be activated at late embryonic stages. In this review, we revisit the recapitulation hypothesis, together with recent molecular-based studies that support the developmental hourglass model. We contend that the recapitulation hypothesis does not entirely contradict the developmental hourglass model and that these two may even coexist in later embryonic stages of vertebrates. Finally, we review possible mechanisms underlying the recapitulation pattern of chromatin accessibility together with the hourglass-like evolutionary conservation in vertebrate embryogenesis., (© 2021 The Authors. Journal of Experimental Zoology Part B: Molecular and Developmental Evolution published by Wiley Periodicals LLC.) more...
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- 2022
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226. Derivedness Index for Estimating Degree of Phenotypic Evolution of Embryos: A Study of Comparative Transcriptomic Analyses of Chordates and Echinoderms.
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Leong JCK, Li Y, Uesaka M, Uchida Y, Omori A, Hao M, Wan W, Dong Y, Ren Y, Zhang S, Zeng T, Wang F, Chen L, Wessel G, Livingston BT, Bradham C, Wang W, and Irie N
- Abstract
Species retaining ancestral features, such as species called living fossils, are often regarded as less derived than their sister groups, but such discussions are usually based on qualitative enumeration of conserved traits. This approach creates a major barrier, especially when quantifying the degree of phenotypic evolution or degree of derivedness, since it focuses only on commonly shared traits, and newly acquired or lost traits are often overlooked. To provide a potential solution to this problem, especially for inter-species comparison of gene expression profiles, we propose a new method named "derivedness index" to quantify the degree of derivedness. In contrast to the conservation-based approach, which deals with expressions of commonly shared genes among species being compared, the derivedness index also considers those that were potentially lost or duplicated during evolution. By applying our method, we found that the gene expression profiles of penta-radial phases in echinoderm tended to be more highly derived than those of the bilateral phase. However, our results suggest that echinoderms may not have experienced much larger modifications to their developmental systems than chordates, at least at the transcriptomic level. In vertebrates, we found that the mid-embryonic and organogenesis stages were generally less derived than the earlier or later stages, indicating that the conserved phylotypic period is also less derived. We also found genes that potentially explain less derivedness, such as Hox genes. Finally, we highlight technical concerns that may influence the measured transcriptomic derivedness, such as read depth and library preparation protocols, for further improvement of our method through future studies. We anticipate that this index will serve as a quantitative guide in the search for constrained developmental phases or processes., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Leong, Li, Uesaka, Uchida, Omori, Hao, Wan, Dong, Ren, Zhang, Zeng, Wang, Chen, Wessel, Livingston, Bradham, Wang and Irie.) more...
- Published
- 2021
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227. Prediction of the motion of chest internal points using a recurrent neural network trained with real-time recurrent learning for latency compensation in lung cancer radiotherapy.
- Author
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Pohl M, Uesaka M, Demachi K, and Bhusal Chhatkuli R
- Subjects
- Algorithms, Humans, Lung, Motion, Lung Neoplasms diagnostic imaging, Lung Neoplasms radiotherapy, Neural Networks, Computer
- Abstract
During the radiotherapy treatment of patients with lung cancer, the radiation delivered to healthy tissue around the tumor needs to be minimized, which is difficult because of respiratory motion and the latency of linear accelerator (LINAC) systems. In the proposed study, we first use the Lucas-Kanade pyramidal optical flow algorithm to perform deformable image registration (DIR) of chest computed tomography (CT) scan images of four patients with lung cancer. We then track three internal points close to the lung tumor based on the previously computed deformation field and predict their position with a recurrent neural network (RNN) trained using real-time recurrent learning (RTRL) and gradient clipping. The breathing data is quite regular, sampled at approximately 2.5 Hz, and includes artificially added drift in the spine direction. The amplitude of the motion of the tracked points ranged from 12.0 mm to 22.7 mm. Finally, we propose a simple method for recovering and predicting three-dimensional (3D) tumor images from the tracked points and the initial tumor image, based on a linear correspondence model and the Nadaraya-Watson non-linear regression. The root-mean-square (RMS) error, maximum error and jitter corresponding to the RNN prediction on the test set were smaller than the same performance measures obtained with linear prediction and least mean squares (LMS). In particular, the maximum prediction error associated with the RNN, equal to 1.51 mm, is respectively 16.1% and 5.0% lower than the error given by a linear predictor and LMS. The average prediction time per time step with RTRL is equal to 119 ms, which is less than the 400 ms marker position sampling time. The tumor position in the predicted images appears visually correct, which is confirmed by the high mean cross-correlation between the original and predicted images, equal to 0.955. The standard deviation of the Gaussian kernel and the number of layers in the optical flow algorithm were the parameters having the most significant impact on registration performance. Their optimization led respectively to a 31.3% and 36.2% decrease in the registration error. Using only a single layer proved to be detrimental to the registration quality because tissue motion in the lower part of the lung has a high amplitude relative to the resolution of the CT scan images. The random initialization of the hidden units and the number of these hidden units were found to be the most important factors affecting the performance of the RNN. Increasing the number of hidden units from 15 to 250 led to a 56.3% decrease in the prediction error on the cross-validation data. Similarly, optimizing the standard deviation of the initial Gaussian distribution of the synaptic weights σ
init RNN led to a 28.4% decrease in the prediction error on the cross-validation data, with the error minimized for σinit RNN =0.02 with the four patients., (Copyright © 2021 Elsevier Ltd. All rights reserved.) more...- Published
- 2021
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228. A computational model of the epidermis with the deformable dermis and its application to skin diseases.
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Ohno K, Kobayashi Y, Uesaka M, Gotoda T, Denda M, Kosumi H, Watanabe M, Natsuga K, and Nagayama M
- Subjects
- Computer Simulation, Homeostasis, Humans, Dermis pathology, Epidermis pathology, Skin Diseases pathology
- Abstract
The skin barrier is provided by the organized multi-layer structure of epidermal cells, which is dynamically maintained by a continuous supply of cells from the basal layer. The epidermal homeostasis can be disrupted by various skin diseases, which often cause morphological changes not only in the epidermis but in the dermis. We present a three-dimensional agent-based computational model of the epidermis that takes into account the deformability of the dermis. Our model can produce a stable epidermal structure with well-organized layers. We show that its stability depends on the cell supply rate from the basal layer. Modeling the morphological change of the dermis also enables us to investigate how the stiffness of the dermis affects the structure and barrier functions of the epidermis. Besides, we show that our model can simulate the formation of a corn (clavus) by assuming hyperproliferation and rapid differentiation. We also provide experimental data for human corn, which supports the model assumptions and the simulation result. more...
- Published
- 2021
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229. Temporal coherency of mechanical stimuli modulates tactile form perception.
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Nakatani M, Kobayashi Y, Ohno K, Uesaka M, Mogami S, Zhao Z, Sushida T, Kitahata H, and Nagayama M
- Subjects
- Data Analysis, Hand physiology, Humans, Models, Theoretical, Psychophysics, Touch, Physical Stimulation, Touch Perception
- Abstract
The human hand can detect both form and texture information of a contact surface. The detection of skin displacement (sustained stimulus) and changes in skin displacement (transient stimulus) are thought to be mediated in different tactile channels; however, tactile form perception may use both types of information. Here, we studied whether both the temporal frequency and the temporal coherency information of tactile stimuli encoded in sensory neurons could be used to recognize the form of contact surfaces. We used the fishbone tactile illusion (FTI), a known tactile phenomenon, as a probe for tactile form perception in humans. This illusion typically occurs with a surface geometry that has a smooth bar and coarse textures in its adjacent areas. When stroking the central bar back and forth with a fingertip, a human observer perceives a hollow surface geometry even though the bar is physically flat. We used a passive high-density pin matrix to extract only the vertical information of the contact surface, suppressing tangential displacement from surface rubbing. Participants in the psychological experiment reported indented surface geometry by tracing over the FTI textures with pin matrices of the different spatial densities (1.0 and 2.0 mm pin intervals). Human participants reported that the relative magnitude of perceived surface indentation steeply decreased when pins in the adjacent areas vibrated in synchrony. To address possible mechanisms for tactile form perception in the FTI, we developed a computational model of sensory neurons to estimate temporal patterns of action potentials from tactile receptive fields. Our computational data suggest that (1) the temporal asynchrony of sensory neuron responses is correlated with the relative magnitude of perceived surface indentation and (2) the spatiotemporal change of displacements in tactile stimuli are correlated with the asynchrony of simulated sensory neuron responses for the fishbone surface patterns. Based on these results, we propose that both the frequency and the asynchrony of temporal activity in sensory neurons could produce tactile form perception. more...
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- 2021
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230. MeCP2 controls neural stem cell fate specification through miR-199a-mediated inhibition of BMP-Smad signaling.
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Nakashima H, Tsujimura K, Irie K, Imamura T, Trujillo CA, Ishizu M, Uesaka M, Pan M, Noguchi H, Okada K, Aoyagi K, Andoh-Noda T, Okano H, Muotri AR, and Nakashima K
- Subjects
- Animals, Cell Differentiation, Disease Models, Animal, Humans, Mice, Signal Transduction, Bone Morphogenetic Protein Receptors metabolism, Methyl-CpG-Binding Protein 2 metabolism, Neural Stem Cells metabolism, Rett Syndrome genetics
- Abstract
Rett syndrome (RTT) is a severe neurological disorder, with impaired brain development caused by mutations in MECP2; however, the underlying mechanism remains elusive. We know from previous work that MeCP2 facilitates the processing of a specific microRNA, miR-199a, by associating with the Drosha complex to regulate neuronal functions. Here, we show that the MeCP2/miR-199a axis regulates neural stem/precursor cell (NS/PC) differentiation. A shift occurs from neuronal to astrocytic differentiation of MeCP2- and miR-199a-deficient NS/PCs due to the upregulation of a miR-199a target, Smad1, a downstream transcription factor of bone morphogenetic protein (BMP) signaling. Moreover, miR-199a expression and treatment with BMP inhibitors rectify the differentiation of RTT patient-derived NS/PCs and development of brain organoids, respectively, suggesting that facilitation of BMP signaling accounts for the impaired RTT brain development. Our study illuminates the molecular pathology of RTT and reveals the MeCP2/miR-199a/Smad1 axis as a potential therapeutic target for RTT., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.) more...
- Published
- 2021
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231. Author Correction: Genomic insights of body plan transitions from bilateral to pentameral symmetry in Echinoderms.
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Li Y, Omori A, Flores RL, Satterfield S, Nguyen C, Ota T, Tsurugaya T, Ikuta T, Ikeo K, Kikuchi M, Leong JCK, Reich A, Hao M, Wan W, Dong Y, Ren Y, Zhang S, Zeng T, Uesaka M, Uchida Y, Li X, Shibata TF, Bino T, Ogawa K, Shigenobu S, Kondo M, Wang F, Chen L, Wessel G, Saiga H, Cameron RA, Livingston B, Bradham C, Wang W, and Irie N more...
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- 2021
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232. Genomic insights of body plan transitions from bilateral to pentameral symmetry in Echinoderms.
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Li Y, Omori A, Flores RL, Satterfield S, Nguyen C, Ota T, Tsurugaya T, Ikuta T, Ikeo K, Kikuchi M, Leong JCK, Reich A, Hao M, Wan W, Dong Y, Ren Y, Zhang S, Zeng T, Uesaka M, Uchida Y, Li X, Shibata TF, Bino T, Ogawa K, Shigenobu S, Kondo M, Wang F, Chen L, Wessel G, Saiga H, Cameron RA, Livingston B, Bradham C, Wang W, and Irie N more...
- Subjects
- Animal Shells anatomy & histology, Animals, Biological Evolution, DNA genetics, Echinodermata anatomy & histology, Echinodermata embryology, Echinodermata growth & development, Gene Library, Genes, Homeobox genetics, Genome genetics, Lytechinus anatomy & histology, Lytechinus growth & development, Phylogeny, Proteomics, Sequence Analysis, DNA, Stichopus anatomy & histology, Stichopus growth & development, Echinodermata genetics, Lytechinus genetics, Stichopus genetics
- Abstract
Echinoderms are an exceptional group of bilaterians that develop pentameral adult symmetry from a bilaterally symmetric larva. However, the genetic basis in evolution and development of this unique transformation remains to be clarified. Here we report newly sequenced genomes, developmental transcriptomes, and proteomes of diverse echinoderms including the green sea urchin (L. variegatus), a sea cucumber (A. japonicus), and with particular emphasis on a sister group of the earliest-diverged echinoderms, the feather star (A. japonica). We learned that the last common ancestor of echinoderms retained a well-organized Hox cluster reminiscent of the hemichordate, and had gene sets involved in endoskeleton development. Further, unlike in other animal groups, the most conserved developmental stages were not at the body plan establishing phase, and genes normally involved in bilaterality appear to function in pentameric axis development. These results enhance our understanding of the divergence of protostomes and deuterostomes almost 500 Mya. more...
- Published
- 2020
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233. Recapitulation-like developmental transitions of chromatin accessibility in vertebrates.
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Uesaka M, Kuratani S, Takeda H, and Irie N
- Abstract
The relationship between development and evolution has been a central theme in evolutionary developmental biology. Across the vertebrates, the most highly conserved gene expression profiles are found at mid-embryonic, organogenesis stages, whereas those at earlier and later stages are more diverged. This hourglass-like pattern of divergence does not necessarily rule out the possibility that gene expression profiles that are more evolutionarily derived appear at later stages of development; however, no molecular-level evidence of such a phenomenon has been reported. To address this issue, we compared putative gene regulatory elements among different species within a phylum. We made a genome-wide assessment of accessible chromatin regions throughout embryogenesis in three vertebrate species (mouse, chicken, and medaka) and estimated the evolutionary ages of these regions to define their evolutionary origins on the phylogenetic tree. In all the three species, we found that genomic regions tend to become accessible in an order that parallels their phylogenetic history, with evolutionarily newer gene regulations activated at later developmental stages. This tendency was restricted only after the mid-embryonic, phylotypic periods. Our results imply a phylogenetic hierarchy of putative regulatory regions, in which their activation parallels the phylogenetic order of their appearance. One evolutionary mechanism that may explain this phenomenon is that newly introduced regulatory elements are more likely to survive if activated at later stages of embryogenesis. Possible relationships between this phenomenon and the so-called recapitulation are discussed., Competing Interests: Competing interestsThe authors declare that they have no competing interests., (© The Author(s). 2019.) more...
- Published
- 2019
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234. Two-Step Transformation of Aliphatic Polyketones into π-Conjugated Polyimines.
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Manabe Y, Uesaka M, Yoneda T, and Inokuma Y
- Abstract
The chemo- and stereo-selective two-step transformation of aliphatic polyketones composed of 3,3-dimethylpentane-2,4-dione units was achieved to generate π-conjugated polyimines. Upon treatment with hydrazine, discrete oligoketones with 4-8 carbonyl groups afforded ethylene-bridged oligoisopyrazoles in 80-89% yields. These oligoisopyrazoles underwent stereoselective oxidation at the ethylene bridge to give fully π-conjugated oligo(isopyrazole-3,5-diyl-trans-vinylene)s in 73-87% yields. Oxidation of the oligoimines drastically changed their absorption and metal-coordination behaviors. Finally, this two-step transformation was applied to polydisperse polymers. Imine formation proceeded almost quantitatively, even for longer polyketones, including docosamer. Subsequent oxidation of the polyimines furnished a virtually insoluble material that showed broad and red-shifted solid-state absorption over the whole visible region resulting from extended π-conjugation. more...
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- 2019
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235. Nucleosome Positioning by an Evolutionarily Conserved Chromatin Remodeler Prevents Aberrant DNA Methylation in Neurospora .
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Klocko AD, Uesaka M, Ormsby T, Rountree MR, Wiles ET, Adhvaryu KK, Honda S, and Selker EU
- Subjects
- Chromatin genetics, Conserved Sequence, Fungal Proteins metabolism, Gene Expression Regulation, Fungal, Histone Code, Methyltransferases metabolism, Neurospora genetics, Nucleosomes metabolism, Chromatin metabolism, DNA Methylation, Fungal Proteins genetics, Methyltransferases genetics, Nucleosomes genetics
- Abstract
In the filamentous fungus Neurospora crassa , constitutive heterochromatin is marked by tri-methylation of histone H3 lysine 9 (H3K9me3) and DNA methylation. We identified mutations in the Neurospora defective in methylation-1 ( dim-1 ) gene that cause defects in cytosine methylation and implicate a putative AAA-ATPase chromatin remodeler. Although it was well-established that chromatin remodelers can affect transcription by influencing DNA accessibility with nucleosomes, little was known about the role of remodelers on chromatin that is normally not transcribed, including regions of constitutive heterochromatin. We found that dim-1 mutants display both reduced DNA methylation in heterochromatic regions as well as increased DNA methylation and H3K9me3 in some intergenic regions associated with highly expressed genes. Deletion of dim-1 leads to atypically spaced nucleosomes throughout the genome and numerous changes in gene expression. DIM-1 localizes to both heterochromatin and intergenic regions that become hyper-methylated in dim-1 strains. Our findings indicate that DIM-1 normally positions nucleosomes in both heterochromatin and euchromatin and that the standard arrangement and density of nucleosomes is required for the proper function of heterochromatin machinery., (Copyright © 2019 by the Genetics Society of America.) more...
- Published
- 2019
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236. Development of a markerless tumor-tracking algorithm using prior four-dimensional cone-beam computed tomography.
- Author
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Bhusal Chhatkuli R, Demachi K, Uesaka M, Nakagawa K, and Haga A
- Subjects
- Humans, Reproducibility of Results, Algorithms, Four-Dimensional Computed Tomography methods, Neoplasms diagnostic imaging
- Abstract
Respiratory motion management is a huge challenge in radiation therapy. Respiratory motion induces temporal anatomic changes that distort the tumor volume and its position. In this study, a markerless tumor-tracking algorithm was investigated by performing phase recognition during stereotactic body radiation therapy (SBRT) using four-dimensional cone-beam computer tomography (4D-CBCT) obtained at patient registration, and in-treatment cone-beam projection images. The data for 20 treatment sessions (five lung cancer patients) were selected for this study. Three of the patients were treated with conventional flattening filter (FF) beams, and the other two were treated with flattening filter-free (FFF) beams. Prior to treatment, 4D-CBCT was acquired to create the template projection images for 10 phases. In-treatment images were obtained at near real time during treatment. Template-based phase recognition was performed for 4D-CBCT re-projected templates using prior 4D-CBCT based phase recognition algorithm and was compared with the results generated by the Amsterdam Shroud (AS) technique. Visual verification technique was used for the verification of the phase recognition and AS technique at certain tumor-visible angles. Offline template matching analysis using the cross-correlation indicated that phase recognition performed using the prior 4D-CBCT and visual verification matched up to 97.5% in the case of FFF, and 95% in the case of FF, whereas the AS technique matched 83.5% with visual verification for FFF and 93% for FF. Markerless tumor tracking based on phase recognition using prior 4D-CBCT has been developed successfully. This is the first study that reports on the use of prior 4D-CBCT based on normalized cross-correlation technique for phase recognition. more...
- Published
- 2019
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237. Mathematical-model-guided development of full-thickness epidermal equivalent.
- Author
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Kumamoto J, Nakanishi S, Makita M, Uesaka M, Yasugahira Y, Kobayashi Y, Nagayama M, Denda S, and Denda M
- Subjects
- Cell Culture Techniques methods, Cell Proliferation, Cells, Cultured, Computer Simulation, Drug Development methods, Filaggrin Proteins, Humans, Infant, Newborn, Keratinocytes cytology, Keratinocytes physiology, Male, Organ Size, Polyesters chemistry, Textiles, Tissue Scaffolds, Epidermis pathology, Models, Theoretical, Skin, Artificial, Tissue Engineering methods
- Abstract
Epidermal equivalents prepared with passaged keratinocytes are typically 10-20 μm thick, whereas intact human epidermis is up to 100 μm thick. Our established mathematical model of epidermal homeostasis predicted that the undulatory pattern of the papillary layer beneath the epidermis is a key determinant of epidermal thickness. Here, we tested this prediction by seeding human keratinocytes on polyester textiles with various fiber-structural patterns in culture dishes exposed to air, aiming to develop a more physiologically realistic epidermal model using passaged keratinocytes. Textile substrate with fiber thickness and inter-fiber distance matching the computer predictions afforded a three-dimensional epidermal-equivalent model with thick stratum corneum and intercellular lamellar lipid structure. The basal layer structure was similar to that of human papillary layer. Cells located around the textile fibers were proliferating, as indicated by BrdU and YAP (Yes-associated protein) staining and expression of melanoma-associated chondroitin sulfate proteoglycan. Filaggrin, loricrin, claudin 1 and ZO-1 were all appropriately expressed. Silencing of transcriptional coactivator YAP with siRNA disturbed construction of the three-dimensional structure. Measurement of trans-epidermal water loss (TEWL) indicated that the model has excellent barrier function. Our results support the idea that mathematical modeling of complex biological processes can have predictive ability and practical value. more...
- Published
- 2018
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238. Role of individual dosimetry for affected residents in postaccident recovery: the Fukushima experience.
- Author
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Naito W and Uesaka M
- Subjects
- Humans, Japan, Fukushima Nuclear Accident, Radiation Dosage, Radiation Monitoring instrumentation, Radiation Protection, Radiometry methods
- Abstract
The accident at Fukushima Daiichi nuclear power plant on 11 March 2011 released radioactive material into the atmosphere, and contaminated land in Fukushima and several neighbouring prefectures. During rehabilitation, it is important to accurately understand and determine individual external doses to allow individuals to make informed decisions about whether or not to return to the affected areas. Personal dosimeters (D-Shuttle), used together with a global positioning system and geographic information system device, can provide realistic individual external doses and associated individual external doses, ambient doses, and activity patterns of individuals in the affected areas of Fukushima. This study involved more than 250 affected residents. The results help to determine realistic individual external doses, and corresponding time-activity patterns and airborne monitoring ambient dose rates, which can be used to predict future cumulative external doses after residents return to their homes in evacuation areas. In addition, insights gained by the study can help to explain the role of individual external dose measurements for affected residents in postaccident recovery, based mainly upon the experience gained in measuring, assessing, and communicating individual external doses. more...
- Published
- 2018
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239. DNA Repair Deficient Chinese Hamster Ovary Cells Exhibiting Differential Sensitivity to Charged Particle Radiation under Aerobic and Hypoxic Conditions.
- Author
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Cartwright IM, Su C, Haskins JS, Salinas VA, Sunada S, Yu H, Uesaka M, Hirakawa H, Chen DJ, Fujimori A, and Kato TA
- Subjects
- Animals, CHO Cells, Cell Hypoxia radiation effects, Cell Survival radiation effects, Cricetinae, Cricetulus, DNA Repair radiation effects, Female, Gamma Rays adverse effects, Linear Energy Transfer, Micronucleus Tests, Ovary metabolism, Oxygen metabolism, Radiation, Ionizing, DNA Damage radiation effects, Ovary cytology, Ovary radiation effects
- Abstract
It has been well established that hypoxia significantly increases both cellular and tumor resistance to ionizing radiation. Hypoxia associated radiation resistance has been known for some time but there has been limited success in sensitizing cells to radiation under hypoxic conditions. These studies show that, when irradiated with low linear energy transfer (LET) gamma-rays, poly (ADP-ribose), polymerase (PARP), Fanconi Anemia (FANC), and mutant Chinese Hamster Ovary (CHO) cells respond similarly to the non-homologous end joining (NHEJ) and the homologous recombination (HR) repair mutant CHO cells. Comparable results were observed in cells exposed to 13 keV/μm carbon ions. However, when irradiated with higher LET spread out Bragg peak (SOBP) carbon ions, we observed a decrease in the oxygen enhancement ratio (OER) in all the DNA of repair mutant cell lines. Interestingly, PARP mutant cells were observed as having the largest decrease in OER. Finally, these studies show a significant increase in the relative biological effectiveness (RBE) of high LET SOBP carbon and iron ions in HR and PARP mutants. There was also an increase in the RBE of NHEJ mutants when irradiated to SOBP carbon and iron ions. However, this increase was lower than in other mutant cell lines. These findings indicate that high LET radiation produces unique types of DNA damage under hypoxic conditions and PARP and HR repair pathways play a role in repairing this damage., Competing Interests: The authors declare no conflict of interest. more...
- Published
- 2018
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240. Design and evaluation of a novel flavonoid-based radioprotective agent utilizing monoglucosyl rutin.
- Author
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Aizawa Y, Sunada S, Hirakawa H, Fujimori A, Kato TA, and Uesaka M
- Subjects
- Animals, Antioxidants pharmacology, Biphenyl Compounds chemistry, CHO Cells, Cell Survival drug effects, Colony-Forming Units Assay, Cricetinae, Cricetulus, Flavonoids chemistry, Free Radical Scavengers pharmacology, Glutathione metabolism, Intracellular Space metabolism, Picrates chemistry, Poly(ADP-ribose) Polymerases metabolism, Radiation-Protective Agents chemistry, Reactive Oxygen Species metabolism, Rutin chemistry, Rutin pharmacology, Solubility, Time Factors, Water chemistry, Flavonoids pharmacology, Radiation-Protective Agents pharmacology, Rutin analogs & derivatives
- Abstract
In this study, three novel flavonoid composite materials, created by combining an aglycone [quercetin (QUE), hesperetin (HES) or naringenin (NAR)] with monoglucosyl rutin (MGR), were designed to test for improved radioprotectivity compared with that provided by administration of MGR alone. Aglycone in the MGR-composite state was highly soluble in water, compared with aglycone alone dissolved in dimethyl sulfoxide or distilled water. The antioxidant activity of the three flavonoid composites was as high as that of MGR only. Next, the cytotoxicity test after 30 min treatment of an MGR composite showed a clear reduction in cell viability and suggested that a rapid introduction of aglycone into cells had taken place. In addition, QUE/MGR and HES/MGR composites strongly scavenged intracellular reactive oxygen species (ROS) induced by X-ray irradiation as well as MGR alone did. However, in the colony-formation assay using irradiated Chinese hamster ovary (CHO) cells, the HES/MGR composite showed a stronger radioprotective effect than MGR alone did, but the QUE/MGR composite showed no additional protective effect compared with the control. Furthermore, it was revealed that QUE and QUE/MGR composite treatment had the effect of reducing the glutathione (GSH) content in cells, and that QUE showed a stronger inhibition of PARP activity compared that of HES and NAR. Our data demonstrated that when designing a flavonoid composite as a radioprotective agent, it was necessary to select an appropriate aglycone, considering not only its antioxidant ability but also its inhibitory effect on cell recovery or DNA repair after radiation injury. more...
- Published
- 2018
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241. Embryonic lethality is not sufficient to explain hourglass-like conservation of vertebrate embryos.
- Author
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Uchida Y, Uesaka M, Yamamoto T, Takeda H, and Irie N
- Abstract
Background: Understanding the general trends in developmental changes during animal evolution, which are often associated with morphological diversification, has long been a central issue in evolutionary developmental biology. Recent comparative transcriptomic studies revealed that gene expression profiles of mid-embryonic period tend to be more evolutionarily conserved than those in earlier or later periods. While the hourglass-like divergence of developmental processes has been demonstrated in a variety of animal groups such as vertebrates, arthropods, and nematodes, the exact mechanism leading to this mid-embryonic conservation remains to be clarified. One possibility is that the mid-embryonic period (pharyngula period in vertebrates) is highly prone to embryonic lethality, and the resulting negative selections lead to evolutionary conservation of this phase. Here, we tested this "mid-embryonic lethality hypothesis" by measuring the rate of lethal phenotypes of three different species of vertebrate embryos subjected to two kinds of perturbations: transient perturbations and genetic mutations., Results: By subjecting zebrafish ( Danio rerio ), African clawed frog ( Xenopus laevis ), and chicken ( Gallus gallus ) embryos to transient perturbations, namely heat shock and inhibitor treatments during three developmental periods [early (represented by blastula and gastrula), pharyngula, and late], we found that the early stages showed the highest rate of lethal phenotypes in all three species. This result was corroborated by perturbation with genetic mutations. By tracking the survival rate of wild-type embryos and embryos with genetic mutations induced by UV irradiation in zebrafish and African clawed frogs, we found that the highest decrease in survival rate was at the early stages particularly around gastrulation in both these species., Conclusion: In opposition to the "mid-embryonic lethality hypothesis," our results consistently showed that the stage with the highest lethality was not around the conserved pharyngula period, but rather around the early period in all the vertebrate species tested. These results suggest that negative selection by embryonic lethality could not explain hourglass-like conservation of animal embryos. This highlights the potential contribution of alternative mechanisms such as the diversifying effect of positive selections against earlier and later stages, and developmental constraints which lead to conservation of mid-embryonic stages. more...
- Published
- 2018
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242. Improved proton CT imaging using a bismuth germanium oxide scintillator.
- Author
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Tanaka S, Nishio T, Tsuneda M, Matsushita K, Kabuki S, and Uesaka M
- Subjects
- Humans, Scintillation Counting methods, Tomography, X-Ray Computed methods, Bismuth chemistry, Germanium chemistry, Image Processing, Computer-Assisted methods, Proton Therapy standards, Scintillation Counting instrumentation, Tomography, X-Ray Computed instrumentation
- Abstract
Range uncertainty is among the most formidable challenges associated with the treatment planning of proton therapy. Proton imaging, which includes proton radiography and proton computed tomography (pCT), is a useful verification tool. We have developed a pCT detection system that uses a thick bismuth germanium oxide (BGO) scintillator and a CCD camera. The current method is based on a previous detection system that used a plastic scintillator, and implements improved image processing techniques. In the new system, the scintillation light intensity is integrated along the proton beam path by the BGO scintillator, and acquired as a two-dimensional distribution with the CCD camera. The range of a penetrating proton is derived from the integrated light intensity using a light-to-range conversion table, and a pCT image can be reconstructed. The proton range in the BGO scintillator is shorter than in the plastic scintillator, so errors due to extended proton ranges can be reduced. To demonstrate the feasibility of the pCT system, an experiment was performed using a 70 MeV proton beam created by the AVF930 cyclotron at the National Institute of Radiological Sciences. The accuracy of the light-to-range conversion table, which is susceptible to errors due to its spatial dependence, was investigated, and the errors in the acquired pixel values were less than 0.5 mm. Images of various materials were acquired, and the pixel-value errors were within 3.1%, which represents an improvement over previous results. We also obtained a pCT image of an edible chicken piece, the first of its kind for a biological material, and internal structures approximately one millimeter in size were clearly observed. This pCT imaging system is fast and simple, and based on these findings, we anticipate that we can acquire 200 MeV pCT images using the BGO scintillator system. more...
- Published
- 2018
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243. Constrained vertebrate evolution by pleiotropic genes.
- Author
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Hu H, Uesaka M, Guo S, Shimai K, Lu TM, Li F, Fujimoto S, Ishikawa M, Liu S, Sasagawa Y, Zhang G, Kuratani S, Yu JK, Kusakabe TG, Khaitovich P, and Irie N
- Subjects
- Animals, Phylogeny, Vertebrates anatomy & histology, Vertebrates growth & development, Biological Evolution, Genetic Pleiotropy, Vertebrates genetics
- Abstract
Despite morphological diversification of chordates over 550 million years of evolution, their shared basic anatomical pattern (or 'bodyplan') remains conserved by unknown mechanisms. The developmental hourglass model attributes this to phylum-wide conserved, constrained organogenesis stages that pattern the bodyplan (the phylotype hypothesis); however, there has been no quantitative testing of this idea with a phylum-wide comparison of species. Here, based on data from early-to-late embryonic transcriptomes collected from eight chordates, we suggest that the phylotype hypothesis would be better applied to vertebrates than chordates. Furthermore, we found that vertebrates' conserved mid-embryonic developmental programmes are intensively recruited to other developmental processes, and the degree of the recruitment positively correlates with their evolutionary conservation and essentiality for normal development. Thus, we propose that the intensively recruited genetic system during vertebrates' organogenesis period imposed constraints on its diversification through pleiotropic constraints, which ultimately led to the common anatomical pattern observed in vertebrates. more...
- Published
- 2017
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244. Oxygen Enhancement Ratio in Radiation-Induced Initial DSBs by an Optimized Flow Cytometry-based Gamma-H2AX Analysis in A549 Human Cancer Cells.
- Author
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Sunada S, Hirakawa H, Fujimori A, Uesaka M, and Okayasu R
- Subjects
- Dose-Response Relationship, Radiation, Flow Cytometry, Humans, Linear Energy Transfer radiation effects, DNA Breaks, Double-Stranded radiation effects, Histones metabolism, Oxygen metabolism
- Abstract
High-linear energy transfer (LET) heavy ions cause higher therapeutic effects than low-LET radiation due to lower dependency on oxygen concentration in tumor cell killing. The lethality after irradiation largely depends on DNA double-strand breaks (DSBs), however the detailed LET dependency for DSB induction under oxic and hypoxic conditions has not been reported. Therefore, we evaluated the oxygen enhancement ratio (OER) of heavy ion-induced DSB induction using a highly-optimized flow cytometry-based method of γ-H2AX detection. Non-small cell lung cancer (NSCLC) A549 cells were exposed to X-ray, carbon-ion and iron-ion radiations under oxic or hypoxic condition. As a DSB marker, the γ-H2AX signal was measured 1 h postirradiation and analyzed by flow cytometry. DSB slope values were calculated as DSB induction per Gy. Our method was able to detect high-LET radiation-induced DSBs even from clustered DNA damage sites. We also showed a decrease in OER value in an LET-dependent manner regardless of radiation type. In summary, we demonstrated a simple, quick and highly-optimized flow cytometry-based method of DSB analysis that detects DSBs induced by heavy-ion radiation for hypoxic and nonhypoxic cancer cells. Our study may provide a useful biological basis for heavy-ion radiotherapy. more...
- Published
- 2017
- Full Text
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245. Measuring and assessing individual external doses during the rehabilitation phase in Iitate village after the Fukushima Daiichi nuclear power plant accident.
- Author
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Naito W, Uesaka M, Kurosawa T, and Kuroda Y
- Subjects
- Decision Making, Female, Geographic Information Systems, Humans, Male, Radiation Monitoring methods, Environmental Exposure adverse effects, Environmental Exposure analysis, Fukushima Nuclear Accident, Radiation Dosage, Radiometry methods
- Abstract
After the Fukushima Daiichi nuclear power plant accident in 2011, Iitate village was placed under an evacuation order because the level of radioactive materials drifting from the nuclear plant to the village was above a government-set level for allowing residents to live in the area. The evacuation advisory for most of the village was lifted on 31 March 2017. For displaced residents deciding whether or not to return to their homes, it is important to correctly understand and estimate the realistic individual external doses they will receive after returning to the village. In this study, with the support of residents of the village, we used a personal dosimeter (D-Shuttle) coupled with a global positioning system device to measure and thus understand realistic individual external doses while the residents were in Iitate village and to project the individual external doses for different administrative districts as of 1 April 2017. The measured individual external doses measured by D-Shuttle for 38 study participants showed that the doses measured during time spent inside the village were higher and more widely distributed than the doses measured during time spent outside the village. The exposure ratio (ER) was defined as the ratio of additional individual external dose measured by D-Shuttle to the additional ambient dose based on an airborne monitoring survey. The medians of the average ERs were 0.13 (min-max 0.06-0.27) for time spent at home and 0.18 (min-max 0.08-0.36) for time spent outdoors. Projected additional annual individual external doses as of 1 April 2017 for different administrative districts in the village were calculated using ERs obtained in this study. Assuming that individuals spent 8 h per day on outdoor activities and 16 h on indoor activities, additional annual individual external doses were estimated to be below 3 mSv using the mean of the average ERs for most districts in the village, and these values were well below the individual external doses estimated using the approach taken by the central government. The results of this study provide valuable information both for understanding realistic radiological situations in the village and for those who want to know their future individual external dose in order to make a decision on whether or not to live in the village. more...
- Published
- 2017
- Full Text
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246. Characterization of micron-size hydrogen clusters using Mie scattering.
- Author
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Jinno S, Tanaka H, Matsui R, Kanasaki M, Sakaki H, Kando M, Kondo K, Sugiyama A, Uesaka M, Kishimoto Y, and Fukuda Y
- Abstract
Hydrogen clusters with diameters of a few micrometer range, composed of 10
8-10 hydrogen molecules, have been produced for the first time in an expansion of supercooled, high-pressure hydrogen gas into a vacuum through a conical nozzle connected to a cryogenic pulsed solenoid valve. The size distribution of the clusters has been evaluated by measuring the angular distribution of laser light scattered from the clusters. The data were analyzed based on the Mie scattering theory combined with the Tikhonov regularization method including the instrumental functions, the validity of which was assessed by performing a calibration study using a reference target consisting of standard micro-particles with two different sizes. The size distribution of the clusters was found discrete peaked at 0.33 ± 0.03, 0.65 ± 0.05, 0.81 ± 0.06, 1.40 ± 0.06 and 2.00 ± 0.13 µm in diameter. The highly reproducible and impurity-free nature of the micron-size hydrogen clusters can be a promising target for laser-driven multi-MeV proton sources with the currently available high power lasers. more...- Published
- 2017
- Full Text
- View/download PDF
247. Investigation of the relative biological effectiveness and uniform isobiological killing effects of irradiation with a clinical carbon SOBP beam on DNA repair deficient CHO cells.
- Author
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Sunada S, Cartwright IM, Hirakawa H, Fujimori A, Uesaka M, and Kato TA
- Abstract
Spread-out Bragg peak (SOBP) C ions have been used clinically in charged particle radiation therapy for years. An SOBP beam consists of various monoenergetic Bragg peaks; however, the biological effect of irradiation with an SOBP beam track has not been well-studied. In order to determine the clinically prospective molecular targets, radiosensitivity to the beam track in DNA repair deficient cell lines was investigated. A total of four distinct Chinese hamster ovary (CHO) cell lines, including CHO10B2 (wild-type), V3 (protein kinase DNA-activated catalytic polypeptide deficient), 51D1 (RAD51 paralog D deficient) and PADR9 [poly(ADP-ribose) polymerase (PARP) deficient], were irradiated with gamma-rays, C ions (290 MeV/n) and Fe ions (500 MeV/n), in order to compare cellular lethality. An OptiCell™ culture system was used to evaluate the lethality at distinct depths of SOBP C ions. Relative biological effectiveness (RBE) values of C ions (linear energy transfer (LET), 13 and 70 keV/µm) and Fe ions (LET, 200 keV/µm) were calculated from cell survival using colony formation assay with standard cell dishes. All cell lines exhibited similar sensitivity to 70 keV/µm C ions and 200 keV/µm Fe ions. Furthermore, V3 cells did not exhibit increased sensitivity to high LET C ions and Fe ions, compared with low LET gamma-rays and C ions, and 51D1 cells irradiated with 13 keV/µm C ions exhibited relatively high RBE values among the tested cell lines. Conversely, PADR9 cells exhibited low RBE values for 13 keV/µm C ions and high RBE values for 70 keV/µm C ions. Obtained using the OptiCell system, the survival fractions in the SOBP region were uniform for wild-type and PADR9 cells. Conversely, V3 and 51D1 cells exhibited decreased cell death in the distal region of the SOBP. These results indicated that PARP is a more effective target for clinical beam therapy, compared with the non-homologous end joining repair and homologous recombination repair pathways. PARP deficiency may be an optimal target for C ion therapy and the results of the present study may contribute to the development of a more effective heavy ion radiation therapy. more...
- Published
- 2017
- Full Text
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248. Evolutionary acquisition of promoter-associated non-coding RNA (pancRNA) repertoires diversifies species-dependent gene activation mechanisms in mammals.
- Author
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Uesaka M, Agata K, Oishi T, Nakashima K, and Imamura T
- Subjects
- Animals, Base Sequence, Epigenesis, Genetic, Gene Expression Profiling, Gene Expression Regulation, Genomics methods, High-Throughput Nucleotide Sequencing, Histones metabolism, Mice, Nucleotide Motifs, Organ Specificity genetics, RNA, Messenger genetics, Evolution, Molecular, Mammals genetics, Promoter Regions, Genetic, RNA, Untranslated genetics, Transcriptional Activation, Transcriptome
- Abstract
Background: Recent transcriptome analyses have shown that long non-coding RNAs (ncRNAs) play extensive roles in transcriptional regulation. In particular, we have reported that promoter-associated ncRNAs (pancRNAs) activate the partner gene expression via local epigenetic changes., Results: Here, we identify thousands of genes under pancRNA-mediated transcriptional activation in five mammalian species in common. In the mouse, 1) pancRNA-partnered genes confined their expression pattern to certain tissues compared to pancRNA-lacking genes, 2) expression of pancRNAs was significantly correlated with the enrichment of active chromatin marks, H3K4 trimethylation and H3K27 acetylation, at the promoter regions of the partner genes, 3) H3K4me1 marked the pancRNA-partnered genes regardless of their expression level, and 4) C- or G-skewed motifs were exclusively overrepresented between-200 and-1 bp relative to the transcription start sites of the pancRNA-partnered genes. More importantly, the comparative transcriptome analysis among five different mammalian species using a total of 25 counterpart tissues showed that the overall pancRNA expression profile exhibited extremely high species-specificity compared to that of total mRNA, suggesting that interspecies difference in pancRNA repertoires might lead to the diversification of mRNA expression profiles., Conclusions: The present study raises the interesting possibility that the gain and/or loss of gene-activation-associated pancRNA repertoires, caused by formation or disruption of the genomic GC-skewed structure in the course of evolution, finely shape the tissue-specific pattern of gene expression according to a given species. more...
- Published
- 2017
- Full Text
- View/download PDF
249. Normal chromosome conformation depends on subtelomeric facultative heterochromatin in Neurospora crassa.
- Author
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Klocko AD, Ormsby T, Galazka JM, Leggett NA, Uesaka M, Honda S, Freitag M, and Selker EU
- Subjects
- Chromobox Protein Homolog 5, Chromosomal Proteins, Non-Histone, Cytosine metabolism, DNA Methylation, DNA, Fungal genetics, Fungal Proteins metabolism, Gene Expression Profiling, Gene Silencing, Genome, Fungal, Histones metabolism, Lysine metabolism, Molecular Conformation, Neurospora crassa genetics, Nucleic Acid Conformation, Sequence Analysis, RNA, Telomere ultrastructure, Chromosomes ultrastructure, Heterochromatin chemistry, Neurospora crassa metabolism
- Abstract
High-throughput chromosome conformation capture (Hi-C) analyses revealed that the 3D structure of the Neurospora crassa genome is dominated by intra- and interchromosomal links between regions of heterochromatin, especially constitutive heterochromatin. Elimination of trimethylation of lysine 9 on histone H3 (H3K9me3) or its binding partner Heterochromatin Protein 1 (HP1)-both prominent features of constitutive heterochromatin-have little effect on the Hi-C pattern. It remained possible that di- or trimethylation of lysine 27 on histone H3 (H3K27me2/3), which becomes localized in regions of constitutive heterochromatin when H3K9me3 or HP1 are lost, plays a critical role in the 3D structure of the genome. We found that H3K27me2/3, catalyzed by the Polycomb Repressive Complex 2 (PRC2) member SET-7 (SET domain protein-7), does indeed play a prominent role in the Hi-C pattern of WT, but that its presence in regions normally occupied by H3K9me3 is not responsible for maintenance of the genome architecture when H3K9me3 is lost. The Hi-C pattern of a mutant defective in the PRC2 member N. crassa p55 (NPF), which is predominantly required for subtelomeric H3K27me2/3, was equivalent to that of the set-7 deletion strain, suggesting that subtelomeric facultative heterochromatin is paramount for normal chromosome conformation. Both PRC2 mutants showed decreased heterochromatin-heterochromatin contacts and increased euchromatin-heterochromatin contacts. Cytological observations suggested elimination of H3K27me2/3 leads to partial displacement of telomere clusters from the nuclear periphery. Transcriptional profiling of Δdim-5, Δset-7, Δset-7; Δdim-5, and Δnpf strains detailed anticipated changes in gene expression but did not support the idea that global changes in genome architecture, per se, led to altered transcription., Competing Interests: The authors declare no conflict of interest. more...
- Published
- 2016
- Full Text
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250. In vitro screening of radioprotective properties in the novel glucosylated flavonoids.
- Author
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Yu H, Haskins JS, Su C, Allum A, Haskins AH, Salinas VA, Sunada S, Inoue T, Aizawa Y, Uesaka M, and Kato TA
- Subjects
- Antioxidants analysis, Biphenyl Compounds chemistry, DNA Breaks, Double-Stranded drug effects, Electrophoresis, Agar Gel, Flavonoids chemistry, Free Radical Scavengers chemistry, Glycosylation drug effects, Nephelometry and Turbidimetry, Picrates chemistry, Radiation-Protective Agents chemistry, Drug Evaluation, Preclinical, Flavonoids analysis, Flavonoids pharmacology, Radiation-Protective Agents analysis, Radiation-Protective Agents pharmacology
- Abstract
Novel glucosyl flavonoids are developed by the addition of glucose to naturally occurring flavonoids. Flavonoids are known antioxidants that possess radioprotective properties. In order to investigate the radioprotective properties of novel glucosyl flavonoids, in vitro DNA double-strand breaks (DSBs) analysis was carried out. In the present study, Quercetin, Naringenin, and Hesperetin groups of flavonoids included in the natural and novel glucosyl 13 flavonoids were investigated. Flavonoids were mixed with Lambda DNA, and subsequently exposed to gamma‑rays. Furthermore, DNA DSB yields were visualized by gel electrophoresis. Quercetin derivatives displayed reduced DNA DSB formation at 10 µM. At a high concentration, the majority of flavonoids displayed radioprotective properties as a reduction of DSB yields. Suppression of DSB formation was confirmed via the molecular combing assay for Quercetin, and three monoglucosyl flavonoids. Glucosylation showed positive effects for radioprotection and monoglucosyl-Rutin showed superior radioprotective properties when compared to monoglucosyl-Naringin and Hesperidin. In addition, Quercetin derivatives had greater total antioxidant capacities and DPPH radical scavenging ability than other flavonoid groups. Since Quercetin, Isoquercetin, and Rutin display poor water solubility, monoglucosyl-Rutin, maltooligosyl-Isoquercetin, and maltooligosyl-Rutin may be better radioprotective agents and easily bioavailable with increased water solubility. more...
- Published
- 2016
- Full Text
- View/download PDF
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