American Association for the Advancement of Science Acta Medica Okayama 2375-2548 11 20 2025 Structure of a photosystem I supercomplex from Galdieria sulphuraria close to an ancestral red alga eadv7488 EN Koji Kato Research institute for interdisciplinary Science and Graduate School of environ-mental, life, natural Science and technology, Okayama University Minoru Kumazawa Graduate School of Agriculture, Kyoto University Yoshiki Nakajima Research institute for interdisciplinary Science and Graduate School of environ-mental, life, natural Science and technology, Okayama University Takehiro Suzuki Biomolecular characterization Unit, RiKen center for Sustainable Resource Science Naoshi Dohmae Biomolecular characterization Unit, RiKen center for Sustainable Resource Science Jian-Ren Shen Research institute for interdisciplinary Science and Graduate School of environ-mental, life, natural Science and technology, Okayama University Kentaro Ifuku Graduate School of Agriculture, Kyoto University Ryo Nagao Faculty of Agriculture, Shizuoka University Red algae exhibit unique photosynthetic adaptations, characterized by photosystem I (PSI) supercomplexes containing light-harvesting complexes (LHCs), forming PSI-LHCI supercomplexes. In this study, we solved the PSI-LHCI structure of Galdieria sulphuraria NIES-3638 at 2.19-angstrom resolution using cryo-electron microscopy, revealing a PSI monomer core associated with seven LHCI subunits. Structural analysis uncovered the absence of phylloquinones, the common secondary electron acceptor in PSI of photosynthetic organisms, suggesting adaptation to a benzoquinone-like molecule. Phylogenetic analysis suggests that G. sulphuraria retains traits characteristic of an ancestral red alga, including distinctive LHCI binding and interaction patterns. Variations in LHCI composition and interactions across red algae, particularly in red-lineage chlorophyll a/b-binding-like protein and red algal LHCs, highlight evolutionary divergence and specialization. These findings not only deepen our understanding of red algal PSI-LHCI diversification but also enable us to predict features of an ancestral red algal PSI-LHCI supercomplex, providing a framework to explore evolutionary adaptations from an ancestral red alga. No potential conflict of interest relevant to this article was reported.

American Association for the Advancement of Science Acta Medica Okayama 2375-2548 9 43 2023 Structure of a diatom photosystem II supercomplex containing a member of Lhcx family and dimeric FCPII eadi8446 EN Yue Feng Photosynthesis Research Center, Key Laboratory of Photobiology, Institute of Botany, Chinese Academy of Sciences Zhenhua Li Photosynthesis Research Center, Key Laboratory of Photobiology, Institute of Botany, Chinese Academy of Sciences Xiaoyi Li Photosynthesis Research Center, Key Laboratory of Photobiology, Institute of Botany, Chinese Academy of Sciences Lili Shen Photosynthesis Research Center, Key Laboratory of Photobiology, Institute of Botany, Chinese Academy of Sciences Xueyang Liu Photosynthesis Research Center, Key Laboratory of Photobiology, Institute of Botany, Chinese Academy of Sciences Cuicui Zhou Photosynthesis Research Center, Key Laboratory of Photobiology, Institute of Botany, Chinese Academy of Sciences Jinyang Zhang Photosynthesis Research Center, Key Laboratory of Photobiology, Institute of Botany, Chinese Academy of Sciences Min Sang China National Botanical Garden Guangye Han Photosynthesis Research Center, Key Laboratory of Photobiology, Institute of Botany, Chinese Academy of Sciences Wenqiang Yang Photosynthesis Research Center, Key Laboratory of Photobiology, Institute of Botany, Chinese Academy of Sciences Tingyun Kuang Photosynthesis Research Center, Key Laboratory of Photobiology, Institute of Botany, Chinese Academy of Sciences Wenda Wang Photosynthesis Research Center, Key Laboratory of Photobiology, Institute of Botany, Chinese Academy of Sciences Jian-Ren Shen Research Institute for Interdisciplinary Science, Graduate School of Natural Science and Technology, Okayama University Diatoms rely on fucoxanthin chlorophyll a/c-binding proteins (FCPs) for their great success in oceans, which have a great diversity in their pigment, protein compositions, and subunit organizations. We report a unique structure of photosystem II (PSII)-FCPII supercomplex from Thalassiosira pseudonana at 2.68-angstrom resolution by cryo-electron microscopy. FCPIIs within this PSII-FCPII supercomplex exist in dimers and monomers, and a homodimer and a heterodimer were found to bind to a PSII core. The FCPII homodimer is formed by Lhcf7 and associates with PSII through an Lhcx family antenna Lhcx6_1, whereas the heterodimer is formed by Lhcf6 and Lhcf11 and connects to the core together with an Lhcf5 monomer through Lhca2 monomer. An extended pigment network consisting of diatoxanthins, diadinoxanthins, fucoxanthins, and chlorophylls a/c is revealed, which functions in efficient light harvesting, energy transfer, and dissipation. These results provide a structural basis for revealing the energy transfer and dissipation mechanisms and also for the structural diversity of FCP antennas in diatoms. No potential conflict of interest relevant to this article was reported.

American Association for the Advancement of Science Acta Medica Okayama 2375-2548 7 5 The structure of the actin filament uncapping complex mediated by twinfilin eabd5271 EN Dennis M. Mwangangi Institute of Molecular and Cell Biology, A*STAR (Agency for Science, Technology and Research) Edward Manser Institute of Molecular and Cell Biology, A*STAR (Agency for Science, Technology and Research) Robert C. Robinson Research Institute for Interdisciplinary Science (RIIS), Okayama University Uncapping of actin filaments is essential for driving polymerization and depolymerization dynamics from capping protein–associated filaments; however, the mechanisms of uncapping leading to rapid disassembly are unknown. Here, we elucidated the x-ray crystal structure of the actin/twinfilin/capping protein complex to address the mechanisms of twinfilin uncapping of actin filaments. The twinfilin/capping protein complex binds to two G-actin subunits in an orientation that resembles the actin filament barbed end. This suggests an unanticipated mechanism by which twinfilin disrupts the stable capping of actin filaments by inducing a G-actin conformation in the two terminal actin subunits. Furthermore, twinfilin disorders critical actin-capping protein interactions, which will assist in the dissociation of capping protein, and may promote filament uncapping through a second mechanism involving V-1 competition for an actin-binding surface on capping protein. The extensive interactions with capping protein indicate that the evolutionary conserved role of twinfilin is to uncap actin filaments. No potential conflict of interest relevant to this article was reported.

American Association for the Advancement of Science Acta Medica Okayama 1946-6234 12 573 2020 Cardiosphere-derived exosomal microRNAs for myocardial repair in pediatric dilated cardiomyopathy eabb3336 EN Kenta Hirai Department of Pediatric Cardiology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Daiki Ousaka Department of Cardiovascular Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Yosuke Fukushima Department of Pediatric Cardiology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Maiko Kondo Department of Pediatric Cardiology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Takahiro Eitoku Department of Pediatric Cardiology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Yusuke Shigemitsu Department of Pediatric Cardiology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Mayuko Hara Department of Pediatric Cardiology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Kenji Baba Department of Pediatric Cardiology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Tatsuo Iwasaki Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Shingo Kasahara Department of Cardiovascular Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Shinichi Ohtsuki Department of Pediatric Cardiology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences Hidemasa Oh Department of Regenerative Medicine, Center for Innovative Clinical Medicine, Okayama University Hospital Although cardiosphere-derived cells (CDCs) improve cardiac function and outcomes in patients with single ventricle physiology, little is known about their safety and therapeutic benefit in children with dilated cardiomyopathy (DCM). We aimed to determine the safety and efficacy of CDCs in a porcine model of DCM and translate the preclinical results into this patient population. A swine model of DCM using intracoronary injection of microspheres created cardiac dysfunction. Forty pigs were randomized as preclinical validation of the delivery method and CDC doses, and CDC-secreted exosome (CDCex)–mediated cardiac repair was analyzed. A phase 1 safety cohort enrolled five pediatric patients with DCM and reduced ejection fraction to receive CDC infusion. The primary endpoint was to assess safety, and the secondary outcome measure was change in cardiac function. Improved cardiac function and reduced myocardial fibrosis were noted in animals treated with CDCs compared with placebo. These functional benefits were mediated via CDCex that were highly enriched with proangiogenic and cardioprotective microRNAs (miRNAs), whereas isolated CDCex did not recapitulate these reparative effects. One-year follow-up of safety lead-in stage was completed with favorable profile and preliminary efficacy outcomes. Increased CDCex-derived miR-146a-5p expression was associated with the reduction in myocardial fibrosis via suppression of proinflammatory cytokines and transcripts. Collectively, intracoronary CDC administration is safe and improves cardiac function through CDCex in a porcine model of DCM. The safety lead-in results in patients provide a translational framework for further studies of randomized trials and CDCex-derived miRNAs as potential paracrine mediators underlying this therapeutic strategy. No potential conflict of interest relevant to this article was reported.

American Association for the Advancement of Science Acta Medica Okayama 2375-2548 5 5 2019 Layer-specific activation of sensory input and predictive feedback in the human primary somatosensory cortex eaav9053 EN Yinghua Yu Graduate School of Interdisciplinary Science and Engineering in Health Systems,Okayama University Laurentius Huber Section on Functional Imaging Methods, National Institute of Mental Health Jiajia Yang Graduate School of Interdisciplinary Science and Engineering in Health Systems,Okayama University David C. Jangraw Section on Functional Imaging Methods, National Institute of Mental Health Daniel A. Handwerker Section on Functional Imaging Methods, National Institute of Mental Health Peter J. Molfese Section on Functional Imaging Methods, National Institute of Mental Health Gang Chen Scientific and Statistical Computing Core, National Institute of Mental Health Yoshimichi Ejima Graduate School of Interdisciplinary Science and Engineering in Health Systems,Okayama University Jinglong Wu Graduate School of Interdisciplinary Science and Engineering in Health Systems,Okayama University Peter A. Bandettini Section on Functional Imaging Methods, National Institute of Mental Health When humans perceive a sensation, their brains integrate inputs from sensory receptors and process them based on their expectations. The mechanisms of this predictive coding in the human somatosensory system are not fully understood. We fill a basic gap in our understanding of the predictive processing of somatosensation by examining the layer-specific activity in sensory input and predictive feedback in the human primary somatosensory cortex (S1). We acquired submillimeter functional magnetic resonance imaging data at 7T (n = 10) during a task of perceived, predictable, and unpredictable touching sequences. We demonstrate that the sensory input from thalamic projects preferentially activates the middle layer, while the superficial and deep layers in S1 are more engaged for cortico-cortical predictive feedback input. These findings are pivotal to understanding the mechanisms of tactile prediction processing in the human somatosensory cortex. No potential conflict of interest relevant to this article was reported.

American Association for the Advancement of Science Acta Medica Okayama 0036-8075 366 6463 2019 An oxyl/oxo mechanism for dioxygen bond formation in PSII revealed by X-ray free electron lasers 334 338 EN Michihiro Suga Research Institute for Interdisciplinary Science and Graduate School of Natural Science and Technology, Okayama University Fusamichi Akita Research Institute for Interdisciplinary Science and Graduate School of Natural Science and Technology, Okayama University Keitaro Yamashita RIKEN SPring-8 Center Yoshiki Nakajima Research Institute for Interdisciplinary Science and Graduate School of Natural Science and Technology, Okayama University Go Ueno RIKEN SPring-8 Center Hongjie Li Research Institute for Interdisciplinary Science and Graduate School of Natural Science and Technology, Okayama University Takahiro Yamane Research Institute for Interdisciplinary Science and Graduate School of Natural Science and Technology, Okayama University Kunio Hirata RIKEN SPring-8 Center Yasufumi Umena Research Institute for Interdisciplinary Science and Graduate School of Natural Science and Technology, Okayama University Shinichiro Yonekura Research Institute for Interdisciplinary Science and Graduate School of Natural Science and Technology, Okayama University Long-Jiang Yu Research Institute for Interdisciplinary Science and Graduate School of Natural Science and Technology, Okayama University Hironori Murakami Japan Synchrotron Radiation Research Institute Takashi Nomura RIKEN SPring-8 Center Tetsunari Kimura Department of Chemistry, Graduate School of Science, Kobe University Minoru Kubo RIKEN SPring-8 Center Seiki Baba Japan Synchrotron Radiation Research Institute Takashi Kumasaka Japan Synchrotron Radiation Research Institute Kensuke Tono RIKEN SPring-8 Center Makina Yabashi RIKEN SPring-8 Center Hiroshi Isobe Research Institute for Interdisciplinary Science and Graduate School of Natural Science and Technology, Okayama University Kizashi Yamaguchi The Institute for Scientific and Industrial Research, Osaka University Masaki Yamamoto RIKEN SPring-8 Center Hideo Ago RIKEN SPring-8 Center Jian-Ren Shen Research Institute for Interdisciplinary Science and Graduate School of Natural Science and Technology, Okayama University Photosynthetic water oxidation is catalyzed by the Mn4CaO5 cluster of photosystem II (PSII) with linear progression through five S-state intermediates (S0 to S4). To reveal the mechanism of water oxidation, we analyzed structures of PSII in the S1, S2, and S3 states by x-ray free-electron laser serial crystallography. No insertion of water was found in S2, but flipping of D1 Glu189 upon transition to S3 leads to the opening of a water channel and provides a space for incorporation of an additional oxygen ligand, resulting in an open cubane Mn4CaO6 cluster with an oxyl/oxo bridge. Structural changes of PSII between the different S states reveal cooperative action of substrate water access, proton release, and dioxygen formation in photosynthetic water oxidation. No potential conflict of interest relevant to this article was reported.