385 results on '"Kyoko WATANABE"'
Search Results
2. Quiescent Infection of Flowers by the Causal Agents of Loquat Fruit Rot, Neopestalotiopsis sp. and Pestalotiopsis sp.
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Shunsuke Nozawa, Masayuki Komine, Yoshiki Takata, Keisuke Uchikawa, Yasuhiro Suga, and Kyoko Watanabe
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disease cycle ,Eriobotrya japonica ,fungal disease ,Neopestalotiopsis ,nit mutant ,Pestalotiopsis ,Plant culture ,SB1-1110 ,Botany ,QK1-989 - Abstract
Loquat fruit rot, caused by Pestalotiopsis sensu lato, is a key problem for loquat producers in Nagasaki Prefecture, the area with the highest loquat fruit production in Japan. In a previous study, it was postulated that fruit rot pathogens latently infect flowers, with the corresponding disease symptoms occurring in wounded fruits. To reveal whether the pathogens responsible for the development of fruit rot disease are found in the asymptomatic flowers and immature fruits of loquat trees, we sprayed a conidial suspension of nitrate-nonutilizing mutants, containing strains derived from pathogenic Neopestalotiopsis sp. (TAP18N004) and Pestalotiopsis sp. (TAP18N010), onto the flowers of “Mogi” and “Nagasaki-wase” trees. Both inoculated mutants were reisolated using selective media (minimal media with chlorate) from the part of the asymptomatic immature fruit that includes the flower apex. Symptoms were observed in the mature fruits of both cultivars, and mutants were specifically detected in the symptomatic tissues of all rotted fruits. Additionally, all reisolated mutants were reconfirmed by assessing corresponding nitrate auxotrophy characteristics. Thus, it was revealed that both fruit rot pathogens that latently infect loquat flowers can cause fruit rot after maturation. [Figure: see text] The author(s) have dedicated the work to the public domain under the Creative Commons CC0 “No Rights Reserved” license by waiving all of his or her rights to the work worldwide under copyright law, including all related and neighboring rights, to the extent allowed by law, 2023.
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- 2023
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3. Changing risk factors for postpartum depression in mothers admitted to a perinatal center
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Yoshihiro Sakemi, Toshinori Nakashima, Kyoko Watanabe, Masayuki Ochiai, Toru Sawano, Hirosuke Inoue, Kosuke Kawakami, Shuichi Isomura, Hironori Yamashita, and Shouichi Ohga
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Edinburgh postnatal depression scale ,Postpartum depression ,Neonatal intensive care unit ,Maternal aging ,Cesarean section ,Pediatrics ,RJ1-570 - Abstract
Background: The Edinburgh postnatal depression scale (EPDS) is commonly used in screening for major postpartum depression (PPD). We explored the clinical factors associated with score changes. Methods: Mothers (n=1,287) who delivered a single live-born infant in Kokura Medical Center in Japan during 2018–2019 were analyzed. The EPDS-Japanese version was conducted at the first and fourth weeks after childbirth. Scores of ≥9 were considered to indicate an increased risk of PPD. Results: The scores improved during the four-week period (5.03±0.12 to 3.79±0.10). Primiparity, Cesarean section (CS), and a low Apgar score were identified as initial risk factors, however, primiparity remained in the multivariate analysis (aOR 2.02, 95% CI 1.37–2.97). Age ≥35 years was associated with worsened scores (aOR 1.88, 95%CI 1.01–3.51), but CS improved (aOR 0.38, 95%CI 0.21–0.70). Primiparity, CS, and neonatal respiratory support were the initial risk factors, while infant anomaly was a late risk factor in mothers whose infants were admitted to the neonatal intensive care unit (NICU) (aOR 3.35, 95%CI 1.31–8.56). In mothers of infants with an NICU stay of ≥4 weeks, infant anomaly was associated with worsened scores (aOR 6.61, 95%CI 1.11–39.3), while respiratory support was associated with improved scores (aOR 0.09, 95%CI 0.01–0.65). Twenty-six mothrs with worsened scores received psychiatric support; three developed PPD. Two of the three were ≥35 years of age, neither of their infants had anomalies. Conclusion: Maternal aging and infant anomaly were risk factors for PPD. PPD occurred in mothers with worsened EPDS scores after mental care. Puerperants with worsening risk factors should be targeted to control PPD.
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- 2023
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4. Specific PCR primer designed from genome data for rapid detection of Fusarium oxysporum f. sp. cubense tropical race 4 in the Cavendish banana.
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Shunsuke Nozawa, Dan Charlie Joy Pangilinan, G Alvindia Dionisio, and Kyoko Watanabe
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Medicine ,Science - Abstract
Fusarium wilt caused by Fusarium oxysporum f. sp. cubense (Foc) tropical race 4 (TR4) severely affects banana production worldwide. Thus, specific PCR primers have been developed to rapidly diagnose and monitor Foc TR4-related fusarium wilt outbreaks in bananas. However, evaluation of these primers revealed room for improvement in the accuracy. This study aimed to design highly specific PCR primers based on genome data for Foc TR4 downloaded from the National Center for Biotechnology Information database. The specificity of the primers was assessed using Foc TR4, Foc races 1 and 2, and 15 other formae speciales strains. The utility of the primers was verified by correctly detecting Foc TR4 in 7 out of 86 isolates of Fusarium spp. obtained from banana farms in the Philippines. The primers allowed for rapid detection in experimentally diseased tissues. We concluded that this novel primer set enables the simplified diagnosis of fusarium wilt caused by Foc TR4 in bananas.
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- 2024
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5. PMS2CL interference leading to erroneous identification of a pathogenic PMS2 variant in Black patients
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Jacqueline Cappadocia, Lisa B. Aiello, Michael J. Kelley, Bryson W. Katona, Kara N. Maxwell, Anurag Verma, Ph.D., Shefali S. Verma, Ph.D., Yuki Bradford, M.S., Ashlei Brock, Stephanie DerOhannessian, Scott Dudek, M.S., Joseph Dunn, Theodore Drivas, M.D., Ph.D., Ned Haubein, Khadijah Hu-Sain, Renae Judy, Ashley Kloter, Yi-An Ko, Meghan Livingstone, Linda Morrel, Colleen Morse, M.S., Afiya Poindexter, Marjorie Risman, M.S., Teo Tran, Fred Vadivieso, JoEllen Weaver, Daniel J. Rader, M.D., Marylyn D. Ritchie, Ph.D., Michael D. Feldman, M.D., Ph.D., Christina Beechert, Caitlin Forsythe, M.S., Erin D. Fuller, Zhenhua Gu, M.S., Michael Lattari, Alexander Lopez, M.S., John D. Overton, Ph.D., Maria Sotiropoulos Padilla, M.S., Manasi Pradhan, M.S., Kia Manoochehri, B.S., Thomas D. Schleicher, M.S., Louis Widom, Sarah E. Wolf, M.S., Ricardo H. Ulloa, B.S., Amelia Averitt, Ph.D., Nilanjana Banerjee, Ph.D., Michael Cantor, M.D., Dadong Li, Ph.D., Sameer Malhotra, M.D., Deepika Sharma, MHI, Jeffrey Staples, Ph.D., Xiaodong Bai, Ph.D., Suganthi Balasubramanian, Ph.D., Suying Bao, Ph.D., Boris Boutkov, Ph.D., Siying Chen, Ph.D., Gisu Eom, B.S., Lukas Habegger, Ph.D., Alicia Hawes, B.S., Shareef Khalid, Olga Krasheninina, M.S., Rouel Lanche, B.S., Adam J. Mansfield, B.A., Evan K. Maxwell, Ph.D., George Mitra, B.A., Mona Nafde, M.S., Sean O’Keeffe, Ph.D., Max Orelus, B.B.A., Razvan Panea, Ph.D., Tommy Polanco, B.A., Ayesha Rasool, M.S., Jeffrey G. Reid, Ph.D., William Salerno, Ph.D., Jeffrey C. Staples, Ph.D., Kathie Sun, Ph.D., Goncalo Abecasis, D.Phil., Joshua Backman, Ph.D., Amy Damask, Ph.D., Lee Dobbyn, Ph.D., Manuel Allen Revez Ferreira, Ph.D., Arkopravo Ghosh, M.S., Christopher Gillies, Ph.D., Lauren Gurski, B.S., Eric Jorgenson, Ph.D., Hyun Min Kang, Ph.D., Michael Kessler, Ph.D., Jack Kosmicki, Ph.D., Alexander Li, Ph.D., Nan Lin, Ph.D., Daren Liu, M.S., Adam Locke, Ph.D., Jonathan Marchini, Ph.D., Anthony Marcketta, M.S., Joelle Mbatchou, Ph.D., Arden Moscati, Ph.D., Charles Paulding, Ph.D., Carlo Sidore, Ph.D., Eli Stahl, Ph.D., Kyoko Watanabe, Ph.D., Bin Ye, Ph.D., Blair Zhang, Ph.D., Andrey Ziyatdinov, Ph.D., Ariane Ayer, B.S., Aysegul Guvenek, Ph.D., George Hindy, Ph.D., Giovanni Coppola, M.D., Jan Freudenberg, M.D., Jonas Bovijn, M.D., Katherine Siminovitch, M.D., Kavita Praveen, Ph.D., Luca A. Lotta, M.D., Manav Kapoor, Ph.D., Mary Haas, Ph.D., Moeen Riaz, Ph.D., Niek Verweij, Ph.D., Olukayode Sosina, Ph.D., Parsa Akbari, Ph.D., Priyanka Nakka, Ph.D., Sahar Gelfman, Ph.D., Sujit Gokhale, B.E., Tanima De, Ph.D., Veera Rajagopal, Ph.D., Alan Shuldiner, M.D., Gannie Tzoneva, Ph.D., Juan Rodriguez-Flores, Ph.D., Esteban Chen, M.S., Marcus B. Jones, Ph.D., Michelle G. LeBlanc, Ph.D., Jason Mighty, Ph.D., Lyndon J. Mitnaul, Ph.D., Nirupama Nishtala, Ph.D., Nadia Rana, Ph.D., Jaimee Hernandez, Goncalo Abecasis, PhD, Aris Baras, M.D., Andrew Deubler, Aris Economides, Ph.D., and Luca A. Lotta, M.D., Ph.D.
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PMS2 ,germline genetic testing ,Lynch syndrome ,PMS2CL ,pseudogene interference ,Genetics ,QH426-470 ,Medicine - Abstract
This study investigates the frequency of a clinically reported variant in PMS2, NM_000535.7:c.2523G>A p.(W841∗), from next-generation sequencing studies in 2 racially diverse cohorts. We identified clinical reports of the PMS2 c.2523G>A p.(W841∗) variant in the National Precision Oncology Program’s somatic testing database (n = 25,168). We determined frequency of the variant in germline exome sequencing from the Penn Medicine BioBank (n = 44,256) and in gnomAD. The PMS2 c.2523G>A p.(W841∗) was identified as a homozygous variant on tumor testing in an adult patient of self-identified Black race/ethnicity with no evidence of constitutional mismatch repair deficiency. The variant was clinically reported on 35 total tumor and liquid biopsy tests (0.1%), and all individuals with the variant were of self-identified Black race/ethnicity (0.6% of n = 5787). In individuals of African genetic ancestry (AFR), the variant's germline frequency was reported to be 0.2% and 1.3% in the Penn Medicine BioBank (PMBB) and gnomAD, respectively. The variant cannot be found in any individuals of European genetic ancestry (EUR) from either of the databases. The variant is found in a region of PMS2 with 100% homology to the PMS2CL pseudogene. PMS2 c.2523G>A p.(W841∗), when identified, is typically an African-ancestry-specific PMS2CL pseudogene variant, which should be recognized to prevent misdiagnosis of Lynch syndrome in Blacks.
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- 2024
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6. Statistical analysis for EUV dynamic spectra and their impact on the ionosphere during solar flares
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Shohei Nishimoto, Kyoko Watanabe, Hidekatsu Jin, Toshiki Kawai, Shinsuke Imada, Tomoko Kawate, Yuichi Otsuka, Atsuki Shinbori, Takuya Tsugawa, and Michi Nishioka
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Solar flare ,X-ray emission ,EUV emission ,Ionosphere ,Space weather ,Geography. Anthropology. Recreation ,Geodesy ,QB275-343 ,Geology ,QE1-996.5 - Abstract
Abstract The X-rays and extreme ultraviolet (EUV) emitted during solar flares can rapidly change the physical composition of Earth’s ionosphere, causing space weather phenomena. It is important to develop an accurate understanding of solar flare emission spectra to understand how it affects the ionosphere. We reproduced the entire solar flare emission spectrum using an empirical model and physics-based model, and input it into the Earth’s atmospheric model, GAIA to calculate the total electron content (TEC) enhancement due to solar flare emission. We compared the statistics of nine solar flare events and calculated the TEC enhancements with the corresponding observed data. The model used in this study was able to estimate the TEC enhancement due to solar flare emission with a correlation coefficient greater than 0.9. The results of this study indicate that the TEC enhancement due to solar flare emission is determined by soft X-ray and EUV emission with wavelengths shorter than 35 nm. The TEC enhancement is found to be largely due to the change in the soft X-ray emission and EUV line emissions with wavelengths, such as Fe XVII 10.08 nm, Fe XIX 10.85 nm and He II 30.38 nm. Graphical Abstract
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- 2023
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7. Description and Pathogenicity of Colletotrichum kapreanum sp. nov, a Cherelle Wilt Pathogen Belonging to the Gigasporum Species Complex
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Yoshiki Takata, Celynne Ocampo-Padilla, Mike Andre C. Malonzo, Dan Charlie Joy Camara Pangilinan, Shunsuke Nozawa, and Kyoko Watanabe
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cherelle wilt ,cacao pod rot ,anthracnose ,Theobroma cacao L. ,Colletotrichum kapreanum ,gigasporum species complex ,Biology (General) ,QH301-705.5 - Abstract
Similar to cacao pod rot, cherelle wilt decreases production from cacao fields. Among all known fungal pathogens of the cacao, Colletotrichum spp. are common infectious agents that affect the cherelles and pods of cacao; thus, cacao diseases are often classified by stage. Therefore, knowing whether these pathogens are common in both fruit stages is necessary for implementing disease control measures. Symptoms of cherelle wilt were found in cacao plants in Pangasinan, Philippines, in 2022. The fungal strain obtained from the lesion was found to be pathogenic towards cherelles, but not towards pods. The strain was classified as an unknown species belonging to the gigasporum species complex, based on the morphological and molecular phylogenetic analyses of ITS, GAPDH, CHS1, ACT, and TUB2. We propose Colletotrichum kapreanum sp. nov. as a causal agent of cacao cherelle wilt, but not pod rot.
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- 2024
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8. Comparison of Solar Multifrequency Microwave Data with Other Solar Indices for Understanding Solar and Stellar Microwave Data
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Masumi Shimojo, Kosuke Namekata, Kazumasa Iwai, Ayumi Asai, and Kyoko Watanabe
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Solar radio emission ,Solar cycle ,Solar atmosphere ,Stellar atmospheres ,Astrophysics ,QB460-466 - Abstract
Thermal microwave emissions detected from stellar atmospheres contain information on stellar activity. However, even for the Sun, the relationship between multifrequency microwave data and other activity indices remains unclear. We investigated the relationships among the thermal microwave fluxes with 1, 2, 3.75, and 9.4 GHz, their circular polarizations, and several activity indices recorded during recent solar cycles and observed that these relationships can be categorized into two groups. In the first group, the relationship between the microwave fluxes and solar indices, which are strongly related to the active regions, can be well-fitted by using a linear function. In the second group, the fitting function is dependent on frequency. Specifically, the microwave fluxes at 1 and 2 GHz can be well-fitted to the total unsigned magnetic and extreme ultraviolet fluxes by employing a power-law function. The trend changes around 3.75 GHz, and the trend for the 9.4 GHz fluxes can be fitted by using a linear function. For the first time, we present the relationship between circular polarization and solar indices. Moreover, we extrapolated these relationships of the solar microwave fluxes to higher values and compared them with the solar-type stars. We found that ϵ Eri, whose microwave emission originates from thermal plasma, follows the extrapolated relationship. However, to date, only one star’s emission at 1–10 GHz has been confirmed as thermal emission. More solar-type stars should be observed with future radio interferometers to confirm that relationships based on solar data can be applied to stellar microwave data.
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- 2024
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9. Detection of Solar Neutrons and Solar Neutron Decay Protons
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Yasushi Muraki, Tatsumi Koi, Satoshi Masuda, Yutaka Matsubara, Pedro Miranda, Shoko Miyake, Tsuguya Naito, Ernesto Ortiz, Akitoshi Oshima, Takashi Sako, Shoichi Shibata, Hisanori Takamaru, Munetoshi Tokumaru, Jóse F. Valdés-Galicia, and Kyoko Watanabe
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solar flare ,impulsive flare ,gradual flare ,solar cosmic rays ,solar energetic particles ,particle acceleration ,Elementary particle physics ,QC793-793.5 - Abstract
Solar flares are broadly classified as impulsive or gradual. Ions accelerated in a gradual flare are thought to be accelerated through a shock acceleration mechanism, but the particle acceleration process in an impulsive flare is still largely unexplored. To understand the acceleration process, it is necessary to measure the high-energy gamma rays and neutrons produced by the impulsive flare. Under such circumstances, on 7 November 2004, a huge X2.0 flare occurred on the solar surface, where ions were accelerated to energies greater than 10 GeV. The accelerated primary protons collided with the solar atmosphere and produced line gamma rays and neutrons. These particles were received as neutrons and line gamma rays, respectively. Neutrons of a few GeV, on the other hand, decay to produce secondary protons while traveling 0.06 au in the solar–terrestrial space. These secondary protons arrive at the magnetopause. Although the flux of secondary protons is very low, the effect of collecting secondary protons arriving in a wide region of the magnetosphere (the Funnel or Horn effect) has resulted in significant signals being received by the solar neutron telescope at Mt. Sierra Negra (4600 m). This information suggests that ions on the solar surface are accelerated to over 10 GeV with an impulsive flare.
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- 2023
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10. PSTEP: project for solar–terrestrial environment prediction
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Kanya Kusano, Kiyoshi Ichimoto, Mamoru Ishii, Yoshizumi Miyoshi, Shigeo Yoden, Hideharu Akiyoshi, Ayumi Asai, Yusuke Ebihara, Hitoshi Fujiwara, Tada-Nori Goto, Yoichiro Hanaoka, Hisashi Hayakawa, Keisuke Hosokawa, Hideyuki Hotta, Kornyanat Hozumi, Shinsuke Imada, Kazumasa Iwai, Toshihiko Iyemori, Hidekatsu Jin, Ryuho Kataoka, Yuto Katoh, Takashi Kikuchi, Yûki Kubo, Satoshi Kurita, Haruhisa Matsumoto, Takefumi Mitani, Hiroko Miyahara, Yasunobu Miyoshi, Tsutomu Nagatsuma, Aoi Nakamizo, Satoko Nakamura, Hiroyuki Nakata, Naoto Nishizuka, Yuichi Otsuka, Shinji Saito, Susumu Saito, Takashi Sakurai, Tatsuhiko Sato, Toshifumi Shimizu, Hiroyuki Shinagawa, Kazuo Shiokawa, Daikou Shiota, Takeshi Takashima, Chihiro Tao, Shin Toriumi, Satoru Ueno, Kyoko Watanabe, Shinichi Watari, Seiji Yashiro, Kohei Yoshida, and Akimasa Yoshikawa
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Solar physics ,Solar–terrestrial environment ,Space weather ,Earth environmental system ,Geography. Anthropology. Recreation ,Geodesy ,QB275-343 ,Geology ,QE1-996.5 - Abstract
Abstract Although solar activity may significantly impact the global environment and socioeconomic systems, the mechanisms for solar eruptions and the subsequent processes have not yet been fully understood. Thus, modern society supported by advanced information systems is at risk from severe space weather disturbances. Project for solar–terrestrial environment prediction (PSTEP) was launched to improve this situation through synergy between basic science research and operational forecast. The PSTEP is a nationwide research collaboration in Japan and was conducted from April 2015 to March 2020, supported by a Grant-in-Aid for Scientific Research on Innovative Areas from the Ministry of Education, Culture, Sports, Science and Technology of Japan. By this project, we sought to answer the fundamental questions concerning the solar–terrestrial environment and aimed to build a next-generation space weather forecast system to prepare for severe space weather disasters. The PSTEP consists of four research groups and proposal-based research units. It has made a significant progress in space weather research and operational forecasts, publishing over 500 refereed journal papers and organizing four international symposiums, various workshops and seminars, and summer school for graduate students at Rikubetsu in 2017. This paper is a summary report of the PSTEP and describes the major research achievements it produced.
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- 2021
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11. Model-based reproduction and validation of the total spectra of a solar flare and their impact on the global environment at the X9.3 event of September 6, 2017
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Kyoko Watanabe, Hidekatsu Jin, Shohei Nishimoto, Shinsuke Imada, Toshiki Kawai, Tomoko Kawate, Yuichi Otsuka, Atsuki Shinbori, Takuya Tsugawa, and Michi Nishioka
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Solar flares ,Dellinger effect ,Total electron content ,Space weather ,Geography. Anthropology. Recreation ,Geodesy ,QB275-343 ,Geology ,QE1-996.5 - Abstract
Abstract We attempted to reproduce the total electron content (TEC) variation in the Earth's atmosphere from the temporal variation of the solar flare spectrum of the X9.3 flare on September 6, 2017. The flare spectrum from the Flare Irradiance Spectral Model (FISM), and the flare spectrum from the 1D hydrodynamic model, which considers the physics of plasma in the flare loop, are used in the GAIA model, which is a simulation model of the Earth's whole atmosphere and ionosphere, to calculate the TEC difference. We then compared these results with the observed TEC. When we used the FISM flare spectrum, the difference in TEC from the background was in a good agreement with the observation. However, when the flare spectrum of the 1D-hydrodynamic model was used, the result varied depending on the presence or absence of the background. This difference depending on the models is considered to represent which extreme ultraviolet (EUV) radiation is primarily responsible for increasing TEC. From the flare spectrum obtained from these models and the calculation result of TEC fluctuation using GAIA, it is considered that the enhancement in EUV emission by approximately 15–35 nm mainly contributes in increasing TEC rather than that of X-ray emission, which is thought to be mainly responsible for sudden ionospheric disturbance. In addition, from the altitude/wavelength distribution of the ionization rate of Earth's atmosphere by GAIA (Ground-to-topside Atmosphere and Ionosphere model for Aeronomy), it was found that EUV radiation of approximately 15–35 nm affects a wide altitude range of 120–300 km, and TEC enhancement is mainly caused by the ionization of nitrogen molecules.
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- 2021
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12. Validation of computed extreme ultraviolet emission spectra during solar flares
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Shohei Nishimoto, Kyoko Watanabe, Toshiki Kawai, Shinsuke Imada, and Tomoko Kawate
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Solar flare ,X-ray emission ,EUV emission ,Space weather ,Geography. Anthropology. Recreation ,Geodesy ,QB275-343 ,Geology ,QE1-996.5 - Abstract
Abstract X-rays and extreme ultraviolet (EUV) emissions from solar flares rapidly change the physical composition of the Earth’s thermosphere and ionosphere, thereby causing space weather phenomena such as communication failures. Numerous empirical and physical models have been developed to estimate the effects of flare emissions on the Earth’s upper atmosphere. We verified the reproduction of the flare emission spectra using a one-dimensional hydrodynamic calculation and the CHIANTI atomic database. To validate the proposed model, we used the observed EUV spectra obtained by the Extreme ultraviolet variability experiment (EVE) on board the Solar Dynamics Observatory (SDO). We examined the “EUV flare time-integrated irradiance” and “EUV flare line rise time” of the EUV emissions for 21 events by comparing the calculation results of the proposed model and observed EUV spectral data. The proposed model successfully reproduced the EUV flare time-integrated irradiance of the Fe VIII 131 Å, Fe XVIII 94 Å, and Fe XX133 Å, as well as the 55–355 Å and 55–135 Å bands. For the EUV flare line rise time, there was an acceptable correlation between the proposed model estimations and observations for all Fe flare emission lines. These results demonstrate that the proposed model can reproduce the EUV flare emission spectra from the emitting plasma with a relatively high formation temperature. This indicates that the physics-based model is effective for the accurate reproduction of the EUV spectral irradiance.
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- 2021
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13. Molecular signatures and cellular diversity during mouse habenula development
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Lieke L. van de Haar, Danai Riga, Juliska E. Boer, Oxana Garritsen, Youri Adolfs, Thomas E. Sieburgh, Roland E. van Dijk, Kyoko Watanabe, Nicky C.H. van Kronenburg, Mark H. Broekhoven, Danielle Posthuma, Frank J. Meye, Onur Basak, and R. Jeroen Pasterkamp
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CP: Neuroscience ,Biology (General) ,QH301-705.5 - Abstract
Summary: The habenula plays a key role in various motivated and pathological behaviors and is composed of molecularly distinct neuron subtypes. Despite progress in identifying mature habenula neuron subtypes, how these subtypes develop and organize into functional brain circuits remains largely unknown. Here, we performed single-cell transcriptional profiling of mouse habenular neurons at critical developmental stages, instructed by detailed three-dimensional anatomical data. Our data reveal cellular and molecular trajectories during embryonic and postnatal development, leading to different habenular subtypes. Further, based on this analysis, our work establishes the distinctive functional properties and projection target of a subtype of Cartpt+ habenula neurons. Finally, we show how comparison of single-cell transcriptional profiles and GWAS data links specific developing habenular subtypes to psychiatric disease. Together, our study begins to dissect the mechanisms underlying habenula neuron subtype-specific development and creates a framework for further interrogation of habenular development in normal and disease states.
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- 2022
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14. Statistical analysis of short-wave fadeout for extreme space weather event estimation
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Chihiro Tao, Michi Nishioka, Susumu Saito, Daikou Shiota, Kyoko Watanabe, Naoto Nishizuka, Takuya Tsugawa, and Mamoru Ishii
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Short-wave fadeout (SWF) ,Dellinger effect ,Ionosphere ,Solar flare ,Ionosonde ,HF radio ,Geography. Anthropology. Recreation ,Geodesy ,QB275-343 ,Geology ,QE1-996.5 - Abstract
Abstract Solar flares trigger an increase in plasma density in the ionosphere including the D region, and cause the absorption of radio waves, especially in high-frequency (HF) ranges, called short-wave fadeout (SWF). To evaluate the SWF duration and absorption statistically, we analyze long-term (36 years) ionosonde data observed by the National Institute of Information and Communications Technology (NICT). The minimum reflection frequency, fmin, is used to detect SWFs from 15-min-resolution ionosonde observations at Kokubunji, Tokyo, from 1981 to 2016. Since fmin varies with local time (LT) and season, we refer to dfmin, which is defined as fmin subtracted by its 27-day running median at the same LT. We find that the occurrence of SWFs detected by three criteria, (i) dfmin ≥ 2.5 MHz, (ii) dfmin ≥ 3.5 MHz, and (iii) blackout, during daytime associated with any flare(s) greater than the C1 class is maximized at local noon and decreases with increasing solar zenith angle. We confirm that the dfmin and duration of SWFs increase with the solar flare class. We estimate the absorption intensity from observations, which is comparable to an empirical relationship obtained from sudden cosmic noise absorption. A generalized empirical relationship for absorption from long-distance circuits shows quantitatively different dependences on solar flare flux, solar zenith angle, and frequency caused by different signal passes compared with that obtained from cosmic noise absorption. From our analysis and the empirical relationships, we estimate the duration of extreme events with occurrence probabilities of once per 10, 100, and 1000 years to be 1.8–3.6, 4.0–6.8, and 7.4–11.9 h, respectively. The longest duration of SWFs of about 12 h is comparable to the solar flare duration derived from an empirical relationship between the solar flare duration and the solar active area for the largest solar active region observed so far.
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- 2020
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15. Genome-wide meta-analysis of brain volume identifies genomic loci and genes shared with intelligence
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Philip R. Jansen, Mats Nagel, Kyoko Watanabe, Yongbin Wei, Jeanne E. Savage, Christiaan A. de Leeuw, Martijn P. van den Heuvel, Sophie van der Sluis, and Danielle Posthuma
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Science - Abstract
Brain volume and intelligence have been previously found to have shared genetic etiology, but the specific common genetic signals have not been identified. Here, the authors perform a genome-wide association study on brain volume, finding common genetic loci driving brain volume and intelligence.
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- 2020
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16. Author Correction: Genetic mapping of cell type specificity for complex traits
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Kyoko Watanabe, Maša Umićević Mirkov, Christiaan A. de Leeuw, Martijn P. van den Heuvel, and Danielle Posthuma
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Science - Abstract
An amendment to this paper has been published and can be accessed via a link at the top of the paper.
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- 2020
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17. Fusarium mindanaoense sp. nov., a New Fusarium Wilt Pathogen of Cavendish Banana from the Philippines Belonging to the F. fujikuroi Species Complex
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Shunsuke Nozawa, Yosuke Seto, Yoshiki Takata, Lalaine Albano Narreto, Reynaldo R. Valle, Keiju Okui, Shigeya Taida, Dionisio G. Alvindia, Renato G. Reyes, and Kyoko Watanabe
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Fusarium wilt ,new species ,SIX gene ,plant disease ,multigene phylogeny ,Biology (General) ,QH301-705.5 - Abstract
The pathogen causing Fusarium wilt in banana is reported to be Fusarium oxysporum f. sp. cubense (FOC). In 2019, wilt symptoms in banana plants (cultivar: Cavendish) in the Philippines were detected, i.e., the yellowing of the leaves and discoloration of the pseudostem and vascular tissue. The fungus isolated from the vascular tissue was found to be pathogenic to Cavendish bananas and was identified as a new species, F. mindanaoense, belonging to the F. fujikuroi species complex (FFSC); species classification was assessed using molecular phylogenetic analyses based on the tef1, tub2, cmdA, rpb1, and rpb2 genes and morphological analyses. A reciprocal blast search using genomic data revealed that this fungus exclusively included the Secreted in Xylem 6 (SIX6) gene among the SIX homologs related to pathogenicity; it exhibited a highly conserved amino acid sequence compared with that of species in the FFSC, but not with that of FOC. This was the first report of Fusarium wilt in Cavendish bananas caused by a species of the genus Fusarium other than those in the F. oxysporum species complex.
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- 2023
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18. Reconstructing the XUV Spectra of Active Sun-like Stars Using Solar Scaling Relations with Magnetic Flux
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Kosuke Namekata, Shin Toriumi, Vladimir S. Airapetian, Munehito Shoda, Kyoko Watanabe, and Yuta Notsu
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Solar x-ray emission ,Extreme ultraviolet astronomy ,Solar extreme ultraviolet emission ,Solar coronal heating ,Stellar x-ray flares ,Stellar coronae ,Astrophysics ,QB460-466 - Abstract
The Kepler space telescope and Transiting Exoplanet Survey Satellite unveiled that Sun-like stars frequently host exoplanets. These exoplanets are subject to fluxes of ionizing radiation in the form of X-ray and extreme-ultraviolet (EUV) radiation that may cause changes in their atmospheric dynamics and chemistry. While X-ray fluxes can be observed directly, EUV fluxes cannot be observed because of severe interstellar medium absorption. Here we present a new empirical method to estimate the whole stellar X-ray plus EUV (XUV) and far-UV (FUV) spectra as a function of total unsigned magnetic fluxes of stars. The response of the solar XUV and FUV spectrum (0.1–180 nm) to the solar total unsigned magnetic flux is investigated by using the long-term Sun-as-a-star data set over 10 yr, and the power-law relation is obtained for each wavelength with a spectral resolution of 0.1–1 nm. We applied the scaling relations to active young Sun-like stars (G dwarfs), EK Dra (G1.5V), π ^1 Uma (G1.5V), and κ ^1 Ceti (G5V) and found that the observed spectra (except for the unobservable longward EUV wavelength) are roughly consistent with the extension of the derived power-law relations with errors of an order of magnitude. This suggests that our model is a valuable method to derive the XUV/FUV fluxes of Sun-like stars, including the EUV band mostly absorbed at wavelengths longward of 36 nm. We also discuss differences between the solar extensions and stellar observations at wavelengths in the 2–30 nm band and conclude that simultaneous observations of magnetic and XUV/FUV fluxes are necessary for further validations.
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- 2023
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19. Systematic assessment of variability in the proteome of iPSC derivatives
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Stephanie D. Beekhuis-Hoekstra, Kyoko Watanabe, Josefin Werme, Christiaan A. de Leeuw, Iryna Paliukhovich, Ka Wan Li, Frank Koopmans, August B. Smit, Danielle Posthuma, and Vivi M. Heine
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Biology (General) ,QH301-705.5 - Abstract
The use of induced pluripotent stem cells (iPSC) to model human complex diseases is gaining popularity as it allows investigation of human cells that are otherwise sparsely available. However, due to its laborious and cost intensive nature, iPSC research is often plagued by limited sample size and putative large variability between clones, decreasing statistical power for detecting experimental effects. Here, we investigate the source and magnitude of variability in the proteome of parallel differentiated astrocytes using mass spectrometry. We compare three possible sources of variability: inter-donor variability, inter- and intra-clonal variability, at different stages of maturation. We show that the interclonal variability is significantly smaller than the inter-donor variability, and that including more donors has a much larger influence on statistical power than adding more clones per donor. Our results provide insight into the sources of variability at protein level between iPSC samples derived in parallel and will aid in optimizing iPSC studies.
- Published
- 2021
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20. Genetic mapping and evolutionary analysis of human-expanded cognitive networks
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Yongbin Wei, Siemon C. de Lange, Lianne H. Scholtens, Kyoko Watanabe, Dirk Jan Ardesch, Philip R. Jansen, Jeanne E. Savage, Longchuan Li, Todd M. Preuss, James K. Rilling, Danielle Posthuma, and Martijn P. van den Heuvel
- Subjects
Science - Abstract
Several cortical association areas have rapidly expanded in size during human evolution, including elements of the central cognitive default mode network (DMN). Here, the authors show that genes highly divergent between humans and other primates (HAR genes) are particularly expressed in these brain regions.
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- 2019
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21. Genetic mapping of cell type specificity for complex traits
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Kyoko Watanabe, Maša Umićević Mirkov, Christiaan A. de Leeuw, Martijn P. van den Heuvel, and Danielle Posthuma
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Science - Abstract
Tissue- and cell type-specific information helps to interpret findings from genome-wide association studies. Here, the authors leverage multiple single cell expression datasets to infer cell type specificity of traits.
- Published
- 2019
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22. Author Correction: Genome-wide meta-analysis of brain volume identifies genomic loci and genes shared with intelligence
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Philip R. Jansen, Mats Nagel, Kyoko Watanabe, Yongbin Wei, Jeanne E. Savage, Christiaan A. de Leeuw, Martijn P. van den Heuvel, Sophie van der Sluis, and Danielle Posthuma
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Science - Published
- 2022
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23. Item-level analyses reveal genetic heterogeneity in neuroticism
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Mats Nagel, Kyoko Watanabe, Sven Stringer, Danielle Posthuma, and Sophie van der Sluis
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Science - Abstract
Neuroticism can be assessed as a composite score of individual items. Here, Nagel et al. perform genetic association studies for 12 neuroticism items and the sum-score and demonstrate genetic heterogeneity at the item-level.
- Published
- 2018
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24. Functional mapping and annotation of genetic associations with FUMA
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Kyoko Watanabe, Erdogan Taskesen, Arjen van Bochoven, and Danielle Posthuma
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Science - Abstract
Prioritizing genetic variants is a major challenge in genome-wide association studies. Here, the authors develop FUMA, a web-based bioinformatics tool that uses a combination of positional, eQTL and chromatin interaction mapping to prioritize likely causal variants and genes.
- Published
- 2017
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25. Activation of TGF-β signaling induces cell death via the unfolded protein response in Fuchs endothelial corneal dystrophy
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Naoki Okumura, Keisuke Hashimoto, Miu Kitahara, Hirokazu Okuda, Emi Ueda, Kyoko Watanabe, Makiko Nakahara, Takahiko Sato, Shigeru Kinoshita, Theofilos Tourtas, Ursula Schlötzer-Schrehardt, Friedrich Kruse, and Noriko Koizumi
- Subjects
Medicine ,Science - Abstract
Abstract Fuchs endothelial corneal dystrophy (FECD) is a slowly progressive bilateral disease of corneal endothelium in which accumulation of extracellular matrix (ECM) and loss of corneal endothelial cells (CECs) are phenotypic features. The corneal endothelium maintains corneal transparency by regulating water hydration; consequently, corneal endothelial dysfunction causes serious vision loss. The only therapy for corneal haziness due to corneal endothelial diseases, including FECD, is corneal transplantation using donor corneas, and no pharmaceutical treatment is available. We provide evidence that the expression levels of transforming growth factor-β (TGF-β) isoforms and TGF-β receptors are high in the corneal endothelium of patients with FECD. A cell model based on patients with FECD shows that TGF-β signaling induced a chronic overload of ECM proteins to the endoplasmic reticulum (ER), thereby enhancing the formation of unfolded protein and triggering the intrinsic apoptotic pathway through the unfolded protein response (UPR). We propose that inhibition of TGF-β signaling may represent a novel therapeutic target that suppresses cell loss as well as the accumulation of ECM in FECD.
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- 2017
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26. Infliximab-Induced Aseptic Meningitis during the Treatment of Psoriatic Arthritis
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Yuki Matsuura-Otsuki, Takaaki Hanafusa, Hiroo Yokozeki, and Kyoko Watanabe
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Infliximab ,Psoriasis ,Psoriatic arthritis ,Aseptic meningitis ,Tumor necrosis factor-α ,Dermatology ,RL1-803 - Abstract
A 42-year-old Japanese man presented with persistent headache during treatment for psoriatic arthritis (PsA) with infliximab. Treatment with infliximab was initiated 3 years before and the psoriatic skin lesions with arthritis were well controlled. However, after 21 doses of infliximab, the skin lesions and joint pain exacerbated and became intractable. Ten days after the dosage of infliximab was increased, the patient experienced headache and nausea with high fever. He had scaly, well-circumscribed erythemas on his trunk, extremities, and deformed nails. He also had swelling and pain in multiple joints. His complete blood and differential leukocyte counts were normal. The level of C-reactive protein was 16.66 mg/dL, whereas anti-infliximab antibodies were absent. Nuchal rigidity was absent and there were no abnormal neurological findings; however, jolt test results were positive. Results from magnetic resonance imaging were normal, whereas those from cerebrospinal fluid (CSF) examination were almost normal. The CSF contained mononuclear cells and was negative for bacteriological cultures, India ink staining, and polymerase chain reaction amplification of herpesvirus group DNA. Headache and nausea improved 2 months after infliximab was discontinued. The patient failed to respond to infliximab treatment for PsA, and we diagnosed infliximab-induced aseptic meningitis. Infliximab was discontinued and treatment with ustekinumab and methotrexate was initiated. Thereafter, the psoriatic skin lesion and joint pain gradually improved. Infliximab-induced aseptic meningitis may be a differential diagnosis when symptoms of meningitis develop during infliximab administration.
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- 2017
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27. Feasibility of a cryopreservation of cultured human corneal endothelial cells.
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Naoki Okumura, Takato Kagami, Kyoko Watanabe, Saori Kadoya, Masakazu Sato, and Noriko Koizumi
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Medicine ,Science - Abstract
Transparency of the cornea is essential for vision and is maintained by the corneal endothelium. Consequently, corneal endothelial decompensation arising from irreversible damage to the corneal endothelium causes severe vision impairment. Until recently, transplantation of donor corneas was the only therapeutic choice for treatment of endothelial decompensation. In 2013, we initiated clinical research into cell-based therapy involving injection of a suspension of cultured human corneal endothelial cells (HCECs), in combination with Rho kinase inhibitor, into the anterior chamber. The aim of the present study was to establish a protocol for cryopreservation of HCECs to allow large-scale commercial manufacturing of these cells. This study focused on the effects of various cryopreservation reagents on HCEC viability. Screening of several commercially available cryopreservation reagents identified Bambanker hRM as an effective agent that maintained a cell viability of 89.4% after 14 days of cryopreservation, equivalent to the cell viability of 89.2% for non-cryopreserved control cells. The use of Bambanker hRM and HCECs at a similar grade to that used clinically for cell based therapy (passage 3-5 and a cell density higher than 2000 cells/mm2) gave a similar cell density for cryopreserved HCECs to that of non-preserved control HCECs after 28 days of cultivation (2099 cells/mm2 and 2111 cells/mm2, respectively). HCECs preserved using Bambanker hRM grew in a similar fashion to non-preserved control HCECs and formed a monolayer sheet-like structure. Cryopreservation of HCECs has multiple advantages including the ability to accumulate stocks of master cells, to transport HCEC stocks, and to manufacture HCECs on demand for use in cell-based treatment of endothelial decompensation.
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- 2019
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28. The cup fungus Pestalopezia brunneopruinosa is Pestalotiopsis gibbosa and belongs to Sordariomycetes.
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Kyoko Watanabe, Shunsuke Nozawa, Tom Hsiang, and Brenda Callan
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Medicine ,Science - Abstract
Pestalopezia brunneopruinosa, the type species of Pestalopezia in Leotiomycetes, produces typical cup-shaped ascomata. Because its asexual morph has conidia comprised of five cells including apical and basal appendages and three pigmented median cells, it was first described as Pestalotia gibbosa, which belongs to Sordariomycetes. This contradiction has not been resolved due to the difficulty in isolating this fungus in culture. In this study, we isolated separate strains from the sexual morph and the asexual morph for molecular analysis. Phylogenetic trees of Sporocadaceae based on internal transcribed spacer, partial β-tubulin, and partial translation elongation factor 1-alpha sequence datasets revealed that both strains fall into the same taxon, in a clade in Pestalotiopsis sensu stricto alongside P. gaultheriae and P. spathulata. We provide the first evidence that fungi producing cup-shaped ascomata in Pestalotiopsis belong to Sordariomycetes, and we have proposed the transfer of Pestalopezia brunneopruinosa to Pestalotiopsis gibbosa.
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- 2018
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29. Possible Involvement of p38 in Mechanisms Underlying Acceleration of Proliferation by 15-Deoxy-Δ12,14-prostaglandin J2 and the Precursors in Leukemia Cell Line THP-1
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Yasutaka Azuma, Kyoko Watanabe, Masataka Date, Michiharu Daito, and Kiyoshi Ohura
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Therapeutics. Pharmacology ,RM1-950 - Abstract
15-Deoxy-Δ12,14-prostaglandin J2 (15dPGJ2), which is a ligand for peroxisome proliferator-activated receptor γ (PPARγ), induced apoptosis of several human tumors including gastric, lung, colon, prostate, and breast. However, the role of PPARγ signals in other types of cancer cells (e.g., leukemia) except solid cancer cells is still unclear. The aim of this study is to evaluate the ability of 15dPGJ2 to modify the proliferation of the human leukemia cell line THP-1. 15dPGJ2 at 5 μM stimulated the proliferation in THP-1 at 24 to 72 h after incubation. In contrast, 15dPGJ2 at concentrations above 10 μM inhibited the proliferation through the induction of apoptosis. PGD2, PGJ2, and Δ12-PGJ2 (ΔPGJ2), precursors of 15dPGJ2, had similar proliferative effects at lower concentrations, whereas they induced apoptosis at high concentrations. 15dPGJ2 and three precursors failed to induce the differentiation in THP-1 as assessed by using the differentiation marker CD11b. FACScan analysis revealed that PGD2 at 5 μM, PGJ2 at 1 μM, ΔPGJ2 at 1 μM and 15dPGJ2 at 5 μM all accelerated cell cycle progression in THP-1. Immunoblotting analysis revealed that PGD2 at 5 μM and 15dPGJ2 at 5 μM inhibited the expression of phospho-p38, phospho-MKK3/MKK6, and phospho-ATF-2, and the expression of Cdk inhibitors including p18, p21, and p27 in THP-1. In contrast, PGJ2 at 1 μM and ΔPGJ2 at 1 μM did not affect their expressions. These results suggest that 15dPGJ2 and PGD2 may, through inactivation of the p38 mitogen-activated protein kinase pathway, inhibit the expression of Cdk inhibitors, leading to acceleration of the THP-1 proliferation. Keywords:: THP-1, proliferation, 15-deoxy-Δ12,14-prostaglandin J2, prostaglandin D2, p38
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- 2004
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30. Phylogenetic Analysis of the Synnema-Producing Genus Synnemapestaloides
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Kyoko Watanabe, Mao Sekiguchi, Toyozo Sato, Tom Hsiang, Shigeru Kaneko, Kazuaki Tanaka, Masaru Kanda, Naoko Fujita, and Shunsuke Nozawa
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Amphisphaeriales ,conidiomatal development ,Sporocadaceae ,Synnemapestaloides ,Biology (General) ,QH301-705.5 - Abstract
Synnemapestaloides rhododendri, the type species of the genus Synnemapestaloides, is a pathogen of Rhododendron brachycarpum. This fungus produces six-celled conidia with appendages at both end cells, and are generated by annellidic conidiogenous cells on the synnema. These conidial structures are similar to those of the genus Pestalotia. The monotypic genus Synnemapestaloides is currently classified in the family Amphisphaeriaceae solely based on conidial morphology. Here we demonstrate that Synnemapestaloides represents a distinct genus in the family Sporocadaceae (Amphisphaeriales) based on differences in the nucleotide sequences of the partial large subunit rDNA gene, the rDNA internal transcribed spacer, and the partial β-tubulin. The genus most closely related to Synnemapestaloides is Seimatosporium and the species most similar to Synnemapestaloides rhododendri is Seim. foliicola which produces short synnema-like conidiomata (sporodochia). These results demonstrate that Seim. foliicola should be transferred to Synnemapestaloides, and also demonstrate that Sporocadaceae can have synnematal in addition to pycnidial and acervular conidiomata.
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- 2016
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31. Understanding quantitative polymerase chain reaction bioanalysis issues before validation planning: Japan Bioanalysis Forum discussion group
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Asako, Uchiyama, Yoichi, Naritomi, Yoshitaka, Hashimoto, Takeshi, Hanada, Kyoko, Watanabe, Kumiko, Kitta, Genki, Suzuki, Takao, Komatsuno, and Takahiro, Nakamura
- Subjects
Medical Laboratory Technology ,Clinical Biochemistry ,General Medicine ,General Pharmacology, Toxicology and Pharmaceutics ,Analytical Chemistry - Abstract
Investigating the biodistribution of cell and gene therapy products may play an important role in evaluating their safety and pharmacology. As quantitative polymerase chain reaction (qPCR) is often used for these analyses, it is essential to improve the reliability of bioanalysis performed using qPCR. In this report, the authors discuss the use of qPCR in nonclinical studies, as it can be used to detect target DNA/RNA and it is quantitative and applicable for long-term analysis. The authors also discuss points to consider during bioanalysis using qPCR and present appropriate validation items and their criteria. The authors anticipate the discussion provided herein to contribute to the development of validation and sample analysis for pharmaceuticals analyzed using qPCR.
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- 2022
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32. Designing New Business Development Program Based on Systems Engineering Methodology with Participatory Systems Analysis in Small and Midsized Enterprise.
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Yoshikazu Tomita, Kyoko Watanabe, and Takashi Maeno
- Published
- 2015
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33. Germline Mutations in CIDEB and Protection against Liver Disease
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Niek Verweij, Mary E. Haas, Jonas B. Nielsen, Olukayode A. Sosina, Minhee Kim, Parsa Akbari, Tanima De, George Hindy, Jonas Bovijn, Trikaldarshi Persaud, Lawrence Miloscio, Mary Germino, Lampros Panagis, Kyoko Watanabe, Joelle Mbatchou, Marcus Jones, Michelle LeBlanc, Suganthi Balasubramanian, Craig Lammert, Sofia Enhörning, Olle Melander, David J. Carey, Christopher D. Still, Tooraj Mirshahi, Daniel J. Rader, Prodromos Parasoglou, Johnathon R. Walls, John D. Overton, Jeffrey G. Reid, Aris Economides, Michael N. Cantor, Brian Zambrowicz, Andrew J. Murphy, Goncalo R. Abecasis, Manuel A.R. Ferreira, Eriks Smagris, Viktoria Gusarova, Mark Sleeman, George D. Yancopoulos, Jonathan Marchini, Hyun M. Kang, Katia Karalis, Alan R. Shuldiner, Giusy Della Gatta, Adam E. Locke, Aris Baras, and Luca A. Lotta
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General Medicine - Published
- 2022
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34. Reidentification of Pestalotiopsis sensu lato causing gray blight of tea in Japan
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Shunsake Nozawa, Masayuki Togawa, and Kyoko Watanabe
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Plant Science ,Agronomy and Crop Science - Published
- 2022
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35. Additional Effect of Luseogliflozin on Semaglutide in Nonalcoholic Steatohepatitis Complicated by Type 2 Diabetes Mellitus: An Open-Label, Randomized, Parallel-Group Study
- Author
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Teruki Miyake, Osamu Yoshida, Bunzo Matsuura, Shinya Furukawa, Masashi Hirooka, Masanori Abe, Yoshio Tokumoto, Yohei Koizumi, Takao Watanabe, Eiji Takeshita, Kotaro Sunago, Atsushi Yukimoto, Kyoko Watanabe, Masumi Miyazaki, Sayaka Kanzaki, Hironobu Nakaguchi, Mitsuhito Koizumu, Yasunori Yamamoto, Teru Kumagi, and Yoichi Hiasa
- Subjects
Endocrinology, Diabetes and Metabolism ,Internal Medicine - Abstract
Untreated nonalcoholic fatty liver may progress to nonalcoholic steatohepatitis (NASH) and cirrhosis and induce hepatocellular carcinoma and liver failure. Type 2 diabetes mellitus (T2DM), often complicated with nonalcoholic fatty liver disease (NAFLD), is a driver of NAFLD progression. Thus, efficacious treatment strategies for patients with coexisting NAFLD and T2DM are important for preventing NAFLD progression. Although previous studies have demonstrated that either sodium-glucose transporter 2 inhibitors (SGLT2is) or glucagon-like peptide 1 receptor agonists (GLP-1 RAs) benefit NASH patients with T2DM, the rate of NASH resolution has not sufficiently improved. Therefore, we developed a protocol for a randomized controlled trial to examine whether the addition of an SGLT2i to the treatment regimen of patients receving a GLP-1 RA (combination therapy), within the therapeutic dose range for T2DM, increases the rate of NASH resolution in patients with coexisting NASH and T2DM.This open-label, randomized, parallel-group study commenced in June 2021, will conclude recruitment in May 2023, and will end by March 2025. Sixty patients with NASH complicated by T2DM are enrolled at the Ehime University Hospital in Toon, Japan. Participants will be randomized into: (1) an intervention group receiving combination therapy with the SGLT2i luseogliflozin 2.5 mg, once daily (Taisho Pharmaceutical, Tokyo, Japan) and the GLP-1 RA semaglutide 0.5 mg, once per week (Novonordisk, Copenhagen, Denmark); and (2) a control group receiving monotherapy with the GLP-1 analog semaglutide. The primary endpoints, which will be ascertained by liver biopsy, are: (1) NASH resolution rate from baseline without worsening of liver fibrosis after 52 weeks of intervention; (2) rate of improvement from baseline of at least 1 point in the NAFLD activity score without worsening of liver fibrosis after 52 weeks of intervention; and (3) rate of improvement from baseline of at least one fibrosis stage without worsening of NASH after 52 weeks of intervention.University Hospital Medical Information Network Clinical Trial Registry (UMIN-CTR) number: UMIN000045003. Japan Registry of Clinical Trials registration number: jRCTs061210009.
- Published
- 2022
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36. Inference of Causal Relationships Between Genetic Risk Factors for Cardiometabolic Phenotypes and Female‐Specific Health Conditions
- Author
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Brenda Xiao, Digna R. Velez Edwards, Anastasia Lucas, Theodore Drivas, Kathryn Gray, Brendan Keating, Chunhua Weng, Gail P. Jarvik, Hakon Hakonarson, Leah Kottyan, Noemie Elhadad, Wei‐Qi Wei, Yuan Luo, Dokyoon Kim, Marylyn Ritchie, Shefali Setia Verma, Goncalo Abecasis, Aris Baras, Michael Cantor, Giovanni Coppola, Andrew Deubler, Aris Economides, Katia Karalis, Luca A. Lotta, John D. Overton, Jeffrey G. Reid, Katherine Siminovitch, Alan Shuldiner, Christina Beechert, Caitlin Forsythe, Erin D. Fuller, Zhenhua Gu, Michael Lattari, Alexander Lopez, Maria Sotiropoulos Padilla, Manasi Pradhan, Kia Manoochehri, Thomas D. Schleicher, Louis Widom, Sarah E. Wolf, Ricardo H. Ulloa, Amelia Averitt, Nilanjana Banerjee, Dadong Li, Sameer Malhotra, Deepika Sharma, Jeffrey Staples, Xiaodong Bai, Suganthi Balasubramanian, Suying Bao, Boris Boutkov, Siying Chen, Gisu Eom, Lukas Habegger, Alicia Hawes, Shareef Khalid, Olga Krasheninina, Rouel Lanche, Adam J. Mansfield, Evan K. Maxwell, George Mitra, Mona Nafde, Sean O’Keeffe, Max Orelus, Razvan Panea, Tommy Polanco, Ayesha Rasool, William Salerno, Jeffrey C. Staples, Kathie Sun, Joshua Backman, Amy Damask, Lee Dobbyn, Manuel Allen Revez Ferreira, Arkopravo Ghosh, Christopher Gillies, Lauren Gurski, Eric Jorgenson, Hyun Min Kang, Michael Kessler, Jack Kosmicki, Alexander Li, Nan Lin, Daren Liu, Adam Locke, Jonathan Marchini, Anthony Marcketta, Joelle Mbatchou, Arden Moscati, Charles Paulding, Carlo Sidore, Eli Stahl, Kyoko Watanabe, Bin Ye, Blair Zhang, Andrey Ziyatdinov, Ariane Ayer, Aysegul Guvenek, George Hindy, Jan Freudenberg, Jonas Bovijn, Kavita Praveen, Manav Kapoor, Mary Haas, Moeen Riaz, Niek Verweij, Olukayode Sosina, Parsa Akbari, Priyanka Nakka, Sahar Gelfman, Sujit Gokhale, Tanima De, Veera Rajagopal, Gannie Tzoneva, Juan Rodriguez‐Flores, Shek Man Chim, Valerio Donato, Daniel Fernandez, Giusy Della Gatta, Alessandro Di Gioia, Kristen Howell, Lori Khrimian, Minhee Kim, Hector Martinez, Lawrence Miloscio, Sheilyn Nunez, Elias Pavlopoulos, Trikaldarshi Persaud, Esteban Chen, Marcus B. Jones, Michelle G. LeBlanc, Jason Mighty, Lyndon J. Mitnaul, Nirupama Nishtala, and Nadia Rana
- Subjects
Cardiology and Cardiovascular Medicine - Abstract
Background Cardiometabolic diseases are highly comorbid, but their relationship with female‐specific or overwhelmingly female‐predominant health conditions (breast cancer, endometriosis, pregnancy complications) is understudied. This study aimed to estimate the cross‐trait genetic overlap and influence of genetic burden of cardiometabolic traits on health conditions unique to women. Methods and Results Using electronic health record data from 71 008 ancestrally diverse women, we examined relationships between 23 obstetrical/gynecological conditions and 4 cardiometabolic phenotypes (body mass index, coronary artery disease, type 2 diabetes, and hypertension) by performing 4 analyses: (1) cross‐trait genetic correlation analyses to compare genetic architecture, (2) polygenic risk score–based association tests to characterize shared genetic effects on disease risk, (3) Mendelian randomization for significant associations to assess cross‐trait causal relationships, and (4) chronology analyses to visualize the timeline of events unique to groups of women with high and low genetic burden for cardiometabolic traits and highlight the disease prevalence in risk groups by age. We observed 27 significant associations between cardiometabolic polygenic scores and obstetrical/gynecological conditions (body mass index and endometrial cancer, body mass index and polycystic ovarian syndrome, type 2 diabetes and gestational diabetes, type 2 diabetes and polycystic ovarian syndrome). Mendelian randomization analysis provided additional evidence of independent causal effects. We also identified an inverse association between coronary artery disease and breast cancer. High cardiometabolic polygenic scores were associated with early development of polycystic ovarian syndrome and gestational hypertension. Conclusions We conclude that polygenic susceptibility to cardiometabolic traits is associated with elevated risk of certain female‐specific health conditions.
- Published
- 2023
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37. Joint testing of rare variant burden scores using non-negative least squares
- Author
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Benjamin Geraghty, Kyoko Watanabe, Joelle Mbatchou, and Yuxin Zou
- Abstract
Gene-based burden tests are a popular and powerful approach for analysis of exome-wide association studies. These approaches combine sets of variants within a gene into a single burden score that is then tested for association. Typically, a range of burden scores are calculated and tested across a range of annotation classes and frequency bins. Correlation between these tests can complicate the multiple testing correction and hamper interpretation of the results. We introduce a new method called the Sparse Burden Association Test (SBAT) that tests the joint set of burden scores under the assumption that causal burden scores act in the same effect direction. The method simultaneously assesses the significance of the model fit and selects the set of burden scores that best explain the association at the same time. Using simulated data, we show that the method is well calibrated and highlight some scenarios where the test outperforms existing gene-based tests. We apply the method to 73 quantitative traits from the UK Biobank which further illustrates the power of the method. This test is implemented in the REGENIE software.
- Published
- 2023
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38. Development of an Automatic Measurement Method for CD8 and PD-1 Positive T Cells Using Image Analysis Software
- Author
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Haruo, Miyata, Yasuto, Akiyama, Akira, Iizuka, Ryota, Kondou, Chie, Maeda, Akari, Kanematsu, Kyoko, Watanabe, Tadashi, Ashizawa, Takeshi, Nagashima, Kenichi, Urakami, Keiichi, Ohshima, Takuya, Kawata, Koji, Muramatsu, Akio, Shiomi, Masanori, Terashima, Takashi, Sugino, Akifumi, Notsu, Keita, Mori, and Ken, Yamaguchi
- Subjects
Male ,Cancer Research ,CD8 Antigens ,Programmed Cell Death 1 Receptor ,General Medicine ,CD8-Positive T-Lymphocytes ,Polymorphism, Single Nucleotide ,Antibodies, Anti-Idiotypic ,Lymphocytes, Tumor-Infiltrating ,Oncology ,Stomach Neoplasms ,Image Processing, Computer-Assisted ,Humans ,Colorectal Neoplasms ,Immune Checkpoint Inhibitors ,Software - Abstract
With the progress in cancer immunotherapy using immune checkpoint blockade (ICB) therapy, histological observations of tumor-infiltrating lymphocyte (TIL) status are needed to evaluate the antitumor effect of ICB using imaging analysis software.Formalin-fixed paraffin-embedded sections obtained from colorectal cancer and gastric cancer patients with more than 500 single nucleotide variants were stained with anti-CD8 and anti-PD-1 antibodies. Based on our own algorithm and imaging analysis software, an automatic TIL measurement method was established and compared to the manual counting methods.In the CD8An imaging software-based automatic measurement could be a simple and useful tool for evaluating the therapeutic effect of cancer immunotherapies in terms of TIL status.
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- 2021
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39. Origin of Solar Storms
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Yoichiro Hanaoka, Kyoko Watanabe, and Seiji Yashiro
- Published
- 2023
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40. Effects of soil types and fertility management practices on soil silicon availability and banana silicon uptake
- Author
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Kazumichi Fujii, Yuri Ichinose, Kazuna Arai, Ken Komatsu, Chie Hayakawa, Dionisio de Guzman Alvindia, Kyoko Watanabe, and Arief Hartono
- Subjects
Soil Science ,Plant Science - Abstract
Although silicon (Si) is one of soil abundant constituents and one of the key elements enhancing plant disease resistance, banana uptake of Si is limited by soil Si availability. It remains unclear what factors regulates soil Si availability and whether banana Si uptake increases with increasing soil Si availability in home garden soils. To test whether soil Si availability and banana leaf SiO2 contents are affected by soil types or fertility management practices, we measured (1) banana leaf SiO2 contents along the gradient of livestock inputs in Andisols of Tanzania and (2) water extractable Si, phosphate-buffer extractable Si, and banana leaf SiO2 in the home garden soils with different degree of volcanic ash admixing and with/without leguminous trees in Indonesia (East Java and East Kalimantan). Livestock dung application increased banana leaf SiO2 contents in the Tanzanian home gardens. Water extractable Si increased with increasing soil pH, but soil phosphate-buffer extractable Si and banana leaf SiO2 contents were strongly regulated by oxalate-extractable Si and andic properties in the Indonesian home gardens. Effects of companion trees (agroforestry) increased banana leaf SiO2 only in two of three Andisols (Java). These results suggest that banana leaf SiO2 contents could be primarily regulated by admixing degree of volcanic parent materials rich in weatherable minerals, but that banana leaf SiO2 contents could also be increased by inputs of livestock dung rich in Si (Tanzania) and agroforestry (Indoensia).
- Published
- 2023
- Full Text
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41. High-energy gamma-rays and neutrons observed in very impulsive solar flare on 2012 June 3
- Author
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Yasushi Muraki, Hiroyasu Tajima, Osamu Okudaira, Kyoko Watanabe, Tokonatu Yamamoto, Kiyokazu Koga, Haruhisa Matsumoto, Yasuyuki T. Tanaka, Kohki Kamiya, Shoichi Shibata, and Satoshi Masuda
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Physics ,Sun: flares ,High energy ,Solar flare ,Space and Planetary Science ,Astrophysics::High Energy Astrophysical Phenomena ,Gamma ray ,Astronomy and Astrophysics ,Neutron ,Astrophysics ,acceleration of particles - Abstract
著者人数: 11名, Number of authors: 11, Accepted: 2021-09-01, 資料番号: PA2210032000
- Published
- 2021
42. The Study of Research Direction about Intelligence of Patient with Schizophrenia : Focusing on Wechsler Adult Intelligence Scale ; WAIS
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Kyoko, Watanabe
- Published
- 2021
43. Germline Mutations in
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Niek, Verweij, Mary E, Haas, Jonas B, Nielsen, Olukayode A, Sosina, Minhee, Kim, Parsa, Akbari, Tanima, De, George, Hindy, Jonas, Bovijn, Trikaldarshi, Persaud, Lawrence, Miloscio, Mary, Germino, Lampros, Panagis, Kyoko, Watanabe, Joelle, Mbatchou, Marcus, Jones, Michelle, LeBlanc, Suganthi, Balasubramanian, Craig, Lammert, Sofia, Enhörning, Olle, Melander, David J, Carey, Christopher D, Still, Tooraj, Mirshahi, Daniel J, Rader, Prodromos, Parasoglou, Johnathon R, Walls, John D, Overton, Jeffrey G, Reid, Aris, Economides, Michael N, Cantor, Brian, Zambrowicz, Andrew J, Murphy, Goncalo R, Abecasis, Manuel A R, Ferreira, Eriks, Smagris, Viktoria, Gusarova, Mark, Sleeman, George D, Yancopoulos, Jonathan, Marchini, Hyun M, Kang, Katia, Karalis, Alan R, Shuldiner, Giusy, Della Gatta, Adam E, Locke, Aris, Baras, and Luca A, Lotta
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Liver ,Liver Diseases ,Exome Sequencing ,Humans ,Genetic Predisposition to Disease ,Apoptosis Regulatory Proteins ,Germ-Line Mutation ,Transaminases - Abstract
Exome sequencing in hundreds of thousands of persons may enable the identification of rare protein-coding genetic variants associated with protection from human diseases like liver cirrhosis, providing a strategy for the discovery of new therapeutic targets.We performed a multistage exome sequencing and genetic association analysis to identify genes in which rare protein-coding variants were associated with liver phenotypes. We conducted in vitro experiments to further characterize associations.The multistage analysis involved 542,904 persons with available data on liver aminotransferase levels, 24,944 patients with various types of liver disease, and 490,636 controls without liver disease. We found that rare coding variants inRare germline mutations in
- Published
- 2022
44. La porosité intime des nuances: Federico Fellini, Jacqueline Risset et la traduction d'Intervista
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Laura Santone, Sophie Guermès, Anne Serre, Marina Geat, Gérald Morin, Kyoko Watanabe, Jean-Michel Ropars, Laura Santone, Sophie Guermès, Dominique Delouche, Gérald Morin, Marina Geat, Anne Serre, Kyoko Watanabe, Sophie Guermès, Santone, Laura, Guermès, Sophie, Serre, Anne, Geat, Marina, Morin, Gérald, Watanabe, Kyoko, and Ropars, Jean-Michel
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Risset, traduzione, doppiaggio, poesia, Dante - Published
- 2022
45. The Study of Research Direction about Women’s Depressive Symptoms : Using Systematic Review
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Kyoko, Watanabe
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- 2021
46. Patient iPSC-derived astrocytes with high polygenic risk for schizophrenia reveals a role for mitochondrial glutamate carrier SLC25A18
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Stephanie Beekhuis-Hoekstra, Karen Laupman, Yongbin Wei, Kyoko Watanabe, Paulien Cornelissen-Steijger, Patrick Sullivan, Danielle Posthuma, and Vivi Heine
- Abstract
Schizophrenia is a highly heritable developmental disorder with often devastating effects on patients and their families. The causal mechanisms behind SCZ remain largely unknown, even after more than a century of research. Astrocytes are increasingly being associated with neuropsychiatric disorders including schizophrenia, yet have gained little attention in research. Therefore, in the current report, we investigate the role of astrocytes in schizophrenia by generating iPSC-derived astrocytes from 21 cases and 10 controls. Cases and controls were selected using a genetically informed strategy to increase statistical power of our study without a need for a priori knowledge of causal pathways. In addition, we selected patients with different genetic risk factors to test the generalization potential of our results. We show that neurons co-cultured with schizophrenia astrocytes have higher VGLUT/VGAT ratios than neurons co-cultured with controls astrocytes. Testing for transcriptional differences highlighted 10 genes that separated cases from controls. Of these, differences in SLC25A18 expression were most pronounced and is potentially driving the synaptic differences which we observed in our astrocyte-neuron co-cultures. Of note, SLC25A18 is encoded in a region that has been repeatedly associated with SCZ and its protein transports glutamate across the inner membrane of mitochondria. Our results confirm the involvement of astrocytes in schizophrenia pathology with a specific role for SLC25A18, and show that astroglia can indeed create neuronal abnormalities previously reported in SCZ (i.e. synaptic imbalance). More specifically, these findings support previous reports on the involvement of glutamate buffering by astrocytes and mitochondrial defects in the disease etiology of schizophrenia.
- Published
- 2022
- Full Text
- View/download PDF
47. Biallelic loss of LDB3 leads to a lethal pediatric dilated cardiomyopathy
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Tamara T. Koopmann, Yalda Jamshidi, Mohammad Naghibi-Sistani, Heleen M. van der Klift, Hassan Birjandi, Zuhair Al-Hassnan, Abdullah Alwadai, Giovanni Zifarelli, Ehsan G. Karimiani, Sahar Sedighzadeh, Amir Bahreini, Nayereh Nouri, Merlene Peter, Kyoko Watanabe, Hermine A. van Duyvenvoorde, Claudia A. L. Ruivenkamp, Aalbertine K. K. Teunissen, Arend D. J. Ten Harkel, Sjoerd G. van Duinen, Monique C. Haak, Carlos E. Prada, Gijs W. E. Santen, and Reza Maroofian
- Subjects
Genetics ,Genetics (clinical) - Abstract
Autosomal dominant variants in LDB3 (also known as ZASP), encoding the PDZ-LIM domain-binding factor, have been linked to a late onset phenotype of cardiomyopathy and myofibrillar myopathy in humans. However, despite knockout mice displaying a much more severe phenotype with premature death, bi-allelic variants in LDB3 have not yet been reported. Here we identify biallelic loss-of-function variants in five unrelated cardiomyopathy families by next generation sequencing. In the first family we identified compound heterozygous LOF variants in LDB3 in a fetus with bilateral talipes and mild left cardiac ventricular enlargement. Ultra-structural examination revealed highly irregular Z-disc formation, and RNA analysis demonstrated little/no expression of LDB3 protein with a functional C-terminal LIM domain in muscle tissue from the affected fetus. In a second family a homozygous LDB3 nonsense variant was identified in a young girl with severe early onset dilated cardiomyopathy with left ventricular non compaction; the same homozygous nonsense variant was identified in a third unrelated female infant with dilated cardiomyopathy. We further identified homozygous LDB3 frameshift variants in two unrelated probands diagnosed with cardiomegaly and severely reduced left ventricular ejection fraction. Our findings demonstrate that recessive LDB3 variants can lead to an early-onset severe human phenotype of cardiomyopathy and myopathy, reminiscent of the knockout mouse phenotype, and supporting a loss of function mechanism.
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- 2022
48. Solar Neutron Spectrometer Onboard a 3U CubeSat
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Satoshi Masuda, Hiromitsu Takahashi, Takaya Inamori, Hiroaki Kawahara, Kikuko Miyata, Kyoko Watanabe, Kazutaka Yamaoka, Kazuhiro Nakazawa, Daiki Nobashi, Y. Sasai, Hiroyasu Tajima, Kazuya Ito, Ji Hyun Park, and Koji Matsushita
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Physics ,Optics ,Spectrometer ,business.industry ,Neutron ,CubeSat ,business - Published
- 2021
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49. Genome-wide analysis reveals extensive genetic overlap between schizophrenia, bipolar disorder, and intelligence
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Shahram Bahrami, Alexey A. Shadrin, Kyoko Watanabe, Oleksandr Frei, Olav B. Smeland, Anders M. Dale, Torill Ueland, Kevin S. O’Connell, Florian Krull, Srdjan Djurovic, Francesco Bettella, Danielle Posthuma, Jeanne E. Savage, Ole A. Andreassen, Nils Eiel Steen, Amsterdam Neuroscience - Complex Trait Genetics, Complex Trait Genetics, Human genetics, and Amsterdam Reproduction & Development (AR&D)
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0301 basic medicine ,False discovery rate ,Adult ,Male ,Multifactorial Inheritance ,Bipolar Disorder ,Intelligence ,Biology ,Polymorphism, Single Nucleotide ,Article ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,0302 clinical medicine ,Polymorphism (computer science) ,Databases, Genetic ,medicine ,Humans ,Cognitive Dysfunction ,Genetic Predisposition to Disease ,Effects of sleep deprivation on cognitive performance ,Bipolar disorder ,Molecular Biology ,Genetics ,Cognition ,medicine.disease ,Psychiatry and Mental health ,030104 developmental biology ,Schizophrenia ,Genetic Loci ,Etiology ,Female ,030217 neurology & neurosurgery ,Genome-Wide Association Study - Abstract
Schizophrenia (SCZ) and bipolar disorder (BD) are severe mental disorders associated with cognitive impairment, which is considered a major determinant of functional outcome. Despite this, the etiology of the cognitive impairment is poorly understood, and no satisfactory cognitive treatments exist. Increasing evidence indicates that genetic risk for SCZ may contribute to cognitive impairment, whereas the genetic relationship between BD and cognitive function remains unclear. Here, we combined large genome-wide association study data on SCZ (n = 82,315), BD (n = 51,710), and general intelligence (n = 269,867) to investigate overlap in common genetic variants using conditional false discovery rate (condFDR) analysis. We observed substantial genetic enrichment in both SCZ and BD conditional on associations with intelligence indicating polygenic overlap. Using condFDR analysis, we leveraged this enrichment to increase statistical power and identified 75 distinct genomic loci associated with both SCZ and intelligence, and 12 loci associated with both BD and intelligence at conjunctional FDR
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- 2020
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50. Infection sources of Pestalotiopsis sensu lato related to loquat fruit rot in Nagasaki Prefecture, Japan
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K. Uchikawa, Shunsuke Nozawa, Y. Suga, and Kyoko Watanabe
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0106 biological sciences ,0301 basic medicine ,Spots ,fungi ,food and beverages ,Plant Science ,Eriobotrya ,Biology ,biology.organism_classification ,01 natural sciences ,Japonica ,03 medical and health sciences ,Horticulture ,030104 developmental biology ,Sensu ,Postharvest ,Leaf spot ,Orchard ,Pestalotiopsis ,Agronomy and Crop Science ,010606 plant biology & botany - Abstract
Fruit rot of loquat [Eriobotrya japonica (Thunb.) D. Don], a postharvest disease caused by Pestalotiopsis sensu lato, seriously damages loquat fruit in Nagasaki Prefecture, where the most loquats are produced in Japan. The disease cycle of fruit rot in the orchard has not been adequately elucidated, although gray leaf spot caused by species of Pestalotiopsis s.l. has been suggested as an inoculum source for fruit rot. To determine the inoculum source of loquat fruit rot, fungal isolates of Pestalotiopsis s.l. from rotten fruits, diseased leaves, and healthy flowers of plants with gray leaf spots were tested for pathogenicity on fruits and leaves with and without wounding. Isolates from rotten fruits were identified as Neopestalotipsis by molecular phylogenetic analyses and were genetically close to the isolates identified as Neopestalotiopsis from leaves and flowers and were pathogenic on leaves and fruits. The other isolates, identified as Pestalotiopsis s.s. from healthy flowers and rotten fruits were pathogenic only on fruits. Thus, Neopestalotiopsis fungi from gray leaf spot are the causal agents of fruit rot. The inoculum source of Pestalotiopsis s.s. fungi was not determined.
- Published
- 2020
- Full Text
- View/download PDF
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