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| WoS | SCOPUS | Document Type | Document Title | Abstract | Authors | Affiliation | ResearcherID (WoS) | AuthorsID (SCOPUS) | Author Email(s) | Journal Name | JCR Abbreviation | ISSN | eISSN | Volume | Issue | WoS Edition | WoS Category | JCR Year | IF | JCR (%) | FWCI | FWCI Update Date | WoS Citation | SCOPUS Citation | Keywords (WoS) | KeywordsPlus (WoS) | Keywords (SCOPUS) | KeywordsPlus (SCOPUS) | Language | Publication Stage | Publication Year | Publication Date | DOI | JCR Link | DOI Link | WOS Link | SCOPUS Link |
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| ○ | ○ | Article | Complete and efficient conversion of plant cell wall hemicellulose into high-value bioproducts by engineered yeast | Cellulosic hydrolysates contain substantial amounts of acetate, which is toxic to fermenting microorganisms. Here, the authors engineer Baker's yeast to co-consume xylose and acetate for triacetic acid lactone production from a hemicellulose hydrolysate of switchgrass. Plant cell wall hydrolysates contain not only sugars but also substantial amounts of acetate, a fermentation inhibitor that hinders bioconversion of lignocellulose. Despite the toxic and non-consumable nature of acetate during glucose metabolism, we demonstrate that acetate can be rapidly co-consumed with xylose by engineered Saccharomyces cerevisiae. The co-consumption leads to a metabolic re-configuration that boosts the synthesis of acetyl-CoA derived bioproducts, including triacetic acid lactone (TAL) and vitamin A, in engineered strains. Notably, by co-feeding xylose and acetate, an enginered strain produces 23.91 g/L TAL with a productivity of 0.29 g/L/h in bioreactor fermentation. This strain also completely converts a hemicellulose hydrolysate of switchgrass into 3.55 g/L TAL. These findings establish a versatile strategy that not only transforms an inhibitor into a valuable substrate but also expands the capacity of acetyl-CoA supply in S. cerevisiae for efficient bioconversion of cellulosic biomass. | Sun, Liang; Lee, Jae Won; Yook, Sangdo; Lane, Stephan; Sun, Ziqiao; Kim, Soo Rin; Jin, Yong-Su | Univ Illinois, Dept Food Sci & Human Nutr, Urbana, IL 61820 USA; Univ Illinois, Carl R Woese Inst Genom Biol, Urbana, IL 61820 USA; Univ Illinois, DOE Ctr Adv Bioenergy & Bioprod Innovat, Urbana, IL 61820 USA; Kyungpook Natl Univ, Sch Food Sci & Biotechnol, Daegu, South Korea | SUN, LIANG/AAY-6618-2021; Jin, Yong-Su/L-4530-2013; Sun, Liang/AAY-6618-2021; Kim, Soo Rin/X-2192-2019 | 57207384254; 57204673498; 57189215759; 56489746700; 57226858652; 36659584200; 57204009076 | ysjin@illinois.edu; | NATURE COMMUNICATIONS | NAT COMMUN | 2041-1723 | 12 | 1 | SCIE | MULTIDISCIPLINARY SCIENCES | 2021 | 17.694 | 7.4 | 2.13 | 2025-07-30 | 43 | 47 | TRIACETIC ACID LACTONE; SACCHAROMYCES-CEREVISIAE; MICROBIAL-PRODUCTION; BATCH CULTURE; XYLOSE; METABOLISM; TRANSPORT; GROWTH; FUELS; CYCLE | Acetyl Coenzyme A; Biomass; Bioreactors; Cell Wall; Fermentation; Lignin; Metabolic Engineering; Polysaccharides; Pyrones; Saccharomyces cerevisiae; Vitamin A; Xylose; Panicum virgatum; Saccharomyces cerevisiae; acetic acid; acetyl coenzyme A; carbon; ergosterol; glucose; hemicellulose; lactone; retinol; xylose; hemicellulose; lignin; lignocellulose; polysaccharide; pyrone derivative; triacetic acid lactone; xylose; bioengineering; bioreactor; cell component; cellulose; detection method; fermentation; metabolism; substrate; yeast; Article; biomass conversion; biotechnological production; biotransformation; carbon source; controlled study; fed batch fermentation; fungal cell wall; gene expression; gene expression level; glucose metabolism; hydrolysis; nonhuman; osmotic stress; oxygen supply; Panicum virgatum; plant cell; productivity; Saccharomyces cerevisiae; transgenic microorganism; yeast cell; biomass; bioreactor; cell wall; fermentation; genetics; metabolic engineering; metabolism; Saccharomyces cerevisiae | English | 2021 | 2021-08-17 | 10.1038/s41467-021-25241-y | 바로가기 | 바로가기 | 바로가기 | 바로가기 | ||||
| ○ | Article | Discovery of widespread transcription initiation at microsatellites predictable by sequence-based deep neural network | Using the Cap Analysis of Gene Expression (CAGE) technology, the FANTOM5 consortium provided one of the most comprehensive maps of transcription start sites (TSSs) in several species. Strikingly, ~72% of them could not be assigned to a specific gene and initiate at unconventional regions, outside promoters or enhancers. Here, we probe these unassigned TSSs and show that, in all species studied, a significant fraction of CAGE peaks initiate at microsatellites, also called short tandem repeats (STRs). To confirm this transcription, we develop Cap Trap RNA-seq, a technology which combines cap trapping and long read MinION sequencing. We train sequence-based deep learning models able to predict CAGE signal at STRs with high accuracy. These models unveil the importance of STR surrounding sequences not only to distinguish STR classes, but also to predict the level of transcription initiation. Importantly, genetic variants linked to human diseases are preferentially found at STRs with high transcription initiation level, supporting the biological and clinical relevance of transcription initiation at STRs. Together, our results extend the repertoire of non-coding transcription associated with DNA tandem repeats and complexify STR polymorphism. © 2021, The Author(s). | Grapotte, Mathys; Saraswat, Manu; Bessière, Chloé; Menichelli, Christophe; Ramilowski, Jordan A.; Severin, Jessica; Hayashizaki, Yoshihide; Itoh, Masayoshi; Tagami, Michihira; Murata, Mitsuyoshi; Kojima-Ishiyama, Miki; Noma, Shohei; Noguchi, Shuhei; Kasukawa, Takeya; Hasegawa, Akira; Suzuki, Harukazu; Nishiyori-Sueki, Hiromi; Frith, Martin C.; Abugessaisa, Imad; Aitken, Stuart; Aken, Bronwen L.; Alam, Intikhab; Alam, Tanvir; Alasiri, Rami; Alhendi, Ahmad M. N.; Alinejad-Rokny, Hamid; Alvarez, Mariano J.; Andersson, Robin; Arakawa, Takahiro; Araki, Marito; Arbel, Taly; Archer, John; Archibald, Alan L.; Arner, Erik; Arner, Peter; Asai, Kiyoshi; Ashoor, Haitham; Astrom, Gaby; Babina, Magda; Baillie, J. Kenneth; Bajic, Vladimir B.; Bajpai, Archana; Baker, Sarah; Baldarelli, Richard M.; Balic, Adam; Bansal, Mukesh; Batagov, Arsen O.; Batzoglou, Serafim; Beckhouse, Anthony G.; Beltrami, Antonio P.; Beltrami, Carlo A.; Bertin, Nicolas; Bhattacharya, Sharmodeep; Bickel, Peter J.; Blake, Judith A.; Blanchette, Mathieu; Bodega, Beatrice; Bonetti, Alessandro; Bono, Hidemasa; Bornholdt, Jette; Bttcher, Michael; Bougouffa, Salim; Boyd, Mette; Breda, Jeremie; Brombacher, Frank; Brown, James B.; Bult, Carol J.; Burroughs, A. Maxwell; Burt, Dave W.; Busch, Annika; Caglio, Giulia; Califano, Andrea; Cameron, Christopher J.; Cannistraci, Carlo V.; Carbone, Alessandra; Carlisle, Ailsa J.; Carninci, Piero; Carter, Kim W.; Cesselli, Daniela; Chang, Jen-Chien; Chen, Julie C.; Chen, Yun; Chierici, Marco; Christodoulou, John; Ciani, Yari; Clark, Emily L.; Coskun, Mehmet; Dalby, Maria; Dalla, Emiliano; Daub, Carsten O.; Davis, Carrie A.; de Hoon, Michiel J. L.; de Rie, Derek; Denisenko, Elena; Deplancke, Bart; Detmar, Michael; Deviatiiarov, Ruslan; Di Bernardo, Diego; Diehl, Alexander D.; Dieterich, Lothar C.; Dimont, Emmanuel; Djebali, Sarah; Dohi, Taeko; Dostie, Jose; Drablos, Finn; Edge, Albert S. B.; Edinger, Matthias; Ehrlund, Anna; Ekwall, Karl; Elofsson, Arne; Endoh, Mitsuhiro; Enomoto, Hideki; Enomoto, Saaya; Faghihi, Mohammad; Fagiolini, Michela; Farach-Carson, Mary C.; Faulkner, Geoffrey J.; Favorov, Alexander; Fernandes, Ana Miguel; Ferrai, Carmelo; Forrest, Alistair R. R.; Forrester, Lesley M.; Forsberg, Mattias; Fort, Alexandre; Francescatto, Margherita; Freeman, Tom C.; Frith, Martin; Fukuda, Shinji; Funayama, Manabu; Furlanello, Cesare; Furuno, Masaaki; Furusawa, Chikara; Gao, Hui; Gazova, Iveta; Gebhard, Claudia; Geier, Florian; Geijtenbeek, Teunis B. H.; Ghosh, Samik; Ghosheh, Yanal; Gingeras, Thomas R.; Gojobori, Takashi; Goldberg, Tatyana; Goldowitz, Daniel; Gough, Julian; Greco, Dario; Gruber, Andreas J.; Guhl, Sven; Guigo, Roderic; Guler, Reto; Gusev, Oleg; Gustincich, Stefano; Ha, Thomas J.; Haberle, Vanja; Hale, Paul; Hallstrom, Bjrn M.; Hamada, Michiaki; Handoko, Lusy; Hara, Mitsuko; Harbers, Matthias; Harrow, Jennifer; Harshbarger, Jayson; Hase, Takeshi; Hashimoto, Kosuke; Hatano, Taku; Hattori, Nobutaka; Hayashi, Ryuhei; Herlyn, Meenhard; Hettne, Kristina; Heutink, Peter; Hide, Winston; Hitchens, Kelly J.; Sui, Shannon Ho; ’t Hoen, Peter A. C.; Hon, Chung Chau; Hori, Fumi; Horie, Masafumi; Horimoto, Katsuhisa; Horton, Paul; Hou, Rui; Huang, Edward; Huang, Yi; Hugues, Richard; Hume, David; Ienasescu, Hans; Iida, Kei; Ikawa, Tomokatsu; Ikemura, Toshimichi; Ikeo, Kazuho; Inoue, Norihiko; Ishizu, Yuri; Ito, Yosuke; Ivshina, Anna V.; Jankovic, Boris R.; Jenjaroenpun, Piroon; Johnson, Rory; Jorgensen, Mette; Jorjani, Hadi; Joshi, Anagha; Jurman, Giuseppe; Kaczkowski, Bogumil; Kai, Chieko; Kaida, Kaoru; Kajiyama, Kazuhiro; Kaliyaperumal, Rajaram; Kaminuma, Eli; Kanaya, Takashi; Kaneda, Hiroshi; Kapranov, Philip; Kasianov, Artem S.; Katayama, Toshiaki; Kato, Sachi; Kawaguchi, Shuji; Kawai, Jun; Kawaji, Hideya; Kawamoto, Hiroshi; Kawamura, Yuki I.; Kawasaki, Satoshi; Kawashima, Tsugumi; Kempfle, Judith S.; Kenna, Tony J.; Kere, Juha; Khachigian, Levon; Kiryu, Hisanori; Kishima, Mami; Kitajima, Hiroyuki; Kitamura, Toshio; Kitano, Hiroaki; Klaric, Enio; Klepper, Kjetil; Klinken, S. Peter; Kloppmann, Edda; Knox, Alan J.; Kodama, Yuichi; Kogo, Yasushi; Kojima, Miki; Kojima, Soichi; Komatsu, Norio; Komiyama, Hiromitsu; Kono, Tsukasa; Koseki, Haruhiko; Koyasu, Shigeo; Kratz, Anton; Kukalev, Alexander; Kulakovskiy, Ivan; Kundaje, Anshul; Kunikata, Hiroshi; Kuo, Richard; Kuo, Tony; Kuraku, Shigehiro; Kuznetsov, Vladimir A.; Kwon, Tae Jun; Larouche, Matt; Lassmann, Timo; Law, Andy; Le-Cao, Kim-Anh; Lecellier, Charles-Henri; Lee, Weonju; Lenhard, Boris; Lennartsson, Andreas; Li, Kang; Li, Ruohan; Lilje, Berit; Lipovich, Leonard; Lizio, Marina; Lopez, Gonzalo; Magi, Shigeyuki; Mak, Gloria K.; Makeev, Vsevolod; Manabe, Riichiro; Mandai, Michiko; Mar, Jessica; Maruyama, Kazuichi; Maruyama, Taeko; Mason, Elizabeth; Mathelier, Anthony; Matsuda, Hideo; Medvedeva, Yulia A.; Meehan, Terrence F.; Mejhert, Niklas; Meynert, Alison; Mikami, Norihisa; Minoda, Akiko; Miura, Hisashi; Miyagi, Yohei; Miyawaki, Atsushi; Mizuno, Yosuke; Morikawa, Hiromasa; Morimoto, Mitsuru; Morioka, Masaki; Morishita, Soji; Moro, Kazuyo; Motakis, Efthymios; Motohashi, Hozumi; Mukarram, Abdul Kadir; Mummery, Christine L.; Mungall, Christopher J.; Murakawa, Yasuhiro; Muramatsu, Masami; Nagasaka, Kazunori; Nagase, Takahide; Nakachi, Yutaka; Nakahara, Fumio; Nakai, Kenta; Nakamura, Kumi; Nakamura, Yasukazu; Nakamura, Yukio; Nakazawa, Toru; Nason, Guy P.; Nepal, Chirag; Nguyen, Quan Hoang; Nielsen, Lars K.; Nishida, Kohji; Nishiguchi, Koji M.; Nishiyori, Hiromi; Nitta, Kazuhiro; Notredame, Cedric; Ogishima, Soichi; Ohkura, Naganari; Ohno, Hiroshi; Ohshima, Mitsuhiro; Ohtsu, Takashi; Okada, Yukinori; Okada-Hatakeyama, Mariko; Okazaki, Yasushi; Oksvold, Per; Orlando, Valerio; Ow, Ghim Sion; Ozturk, Mumin; Pachkov, Mikhail; Paparountas, Triantafyllos; Parihar, Suraj P.; Park, Sung-Joon; Pascarella, Giovanni; Passier, Robert; Persson, Helena; Philippens, Ingrid H.; Piazza, Silvano; Plessy, Charles; Pombo, Ana; Ponten, Fredrik; Poulain, Stéphane; Poulsen, Thomas M.; Pradhan, Swati; Prezioso, Carolina; Pridans, Clare; Qin, Xiang-Yang; Quackenbush, John; Rackham, Owen; Ravasi, Timothy; Rehli, Michael; Rennie, Sarah; Rito, Tiago; Rizzu, Patrizia; Robert, Christelle; Roos, Marco; Rost, Burkhard; Roudnicky, Filip; Roy, Riti; Rye, Morten B.; Sachenkova, Oxana; Saetrom, Pal; Sai, Hyonmi; Saiki, Shinji; Saito, Mitsue; Saito, Akira; Sakaguchi, Shimon; Sakai, Mizuho; Sakaue, Saori; Sakaue-Sawano, Asako; Sandelin, Albin; Sano, Hiromi; Sasamoto, Yuzuru; Sato, Hiroki; Saxena, Alka; Saya, Hideyuki; Schafferhans, Andrea; Schmeier, Sebastian; Schmidl, Christian; Schmocker, Daniel; Schneider, Claudio; Schueler, Marcus; Schultes, Erik A.; Schulze-Tanzil, Gundula; Semple, Colin A.; Seno, Shigeto; Seo, Wooseok; Sese, Jun; Sheng, Guojun; Shi, Jiantao; Shimoni, Yishai; Shin, Jay W.; SimonSanchez, Javier; Sivertsson, Asa; Sjostedt, Evelina; Soderhall, Cilla; Laurent, Georges St; Stoiber, Marcus H.; Sugiyama, Daisuke; Summers, Kim M.; Suzuki, Ana Maria; Suzuki, Kenji; Suzuki, Mikiko; Suzuki, Naoko; Suzuki, Takahiro; Swanson, Douglas J.; Swoboda, Rolf K.; Taguchi, Ayumi; Takahashi, Hazuki; Takahashi, Masayo; Takamochi, Kazuya; Takeda, Satoru; Takenaka, Yoichi; Tam, Kin Tung; Tanaka, Hiroshi; Tanaka, Rica; Tanaka, Yuji; Tang, Dave; Taniuchi, Ichiro; Tanzer, Andrea; Tarui, Hiroshi; Taylor, Martin S.; Terada, Aika; Terao, Yasuhisa; Testa, Alison C.; Thomas, Mark; Thongjuea, Supat; Tomii, Kentaro; Triglia, Elena Torlai; Toyoda, Hiroo; Tsang, H. Gwen; Tsujikawa, Motokazu; Uhlén, Mathias; Valen, Eivind; van de Wetering, Marc; van Nimwegen, Erik; Velmeshev, Dmitry; Verardo, Roberto; Vitezic, Morana; Vitting-Seerup, Kristoffer; von Feilitzen, Kalle; Voolstra, Christian R.; Vorontsov, Ilya E.; Wahlestedt, Claes; Wasserman, Wyeth W.; Watanabe, Kazuhide; Watanabe, Shoko; Wells, Christine A.; Winteringham, Louise N.; Wolvetang, Ernst; Yabukami, Haruka; Yagi, Ken; Yamada, Takuji; Yamaguchi, Yoko; Yamamoto, Masayuki; Yamamoto, Yasutomo; Yamamoto, Yumiko; Yamanaka, Yasunari; Yano, Kojiro; Yasuzawa, Kayoko; Yatsuka, Yukiko; Yo, Masahiro; Yokokura, Shunji; Yoneda, Misako; Yoshida, Emiko; Yoshida, Yuki; Yoshihara, Masahito; Young, Rachel; Young, Robert S.; Yu, Nancy Y.; Yumoto, Noriko; Zabierowski, Susan E.; Zhang, Peter G.; Zucchelli, Silvia; Zwahlen, Martin; Chatelain, Clément; de Hoon, Michiel J. L.; Bréhélin, Laurent | Institut de Biologie Computationnelle, Montpellier, France, Institut de Génétique Moléculaire de Montpellier, University of Montpellier, CNRS, Montpellier, France, SANOFI R&D, Translational Sciences, Chilly Mazarin, France; Institut de Biologie Computationnelle, Montpellier, France, Institut de Génétique Moléculaire de Montpellier, University of Montpellier, CNRS, Montpellier, France; Institut de Biologie Computationnelle, Montpellier, France, Institut de Génétique Moléculaire de Montpellier, University of Montpellier, CNRS, Montpellier, France; Institut de Biologie Computationnelle, Montpellier, France, LIRMM, Univ Montpellier, CNRS, Montpellier, France; RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa, Japan, Division of Genomic Technologies, RIKEN Center for Life Science Technologies, Yokohama, Japan, RIKEN Omics Science Center (OSC), Yokohama, Japan; RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa, Japan, Division of Genomic Technologies, RIKEN Center for Life Science Technologies, Yokohama, Japan, RIKEN Omics Science Center (OSC), Yokohama, Japan; RIKEN Preventive Medicine and Diagnosis Innovation Program, Wako, Saitama, Japan, RIKEN Omics Science Center (OSC), Yokohama, Japan; RIKEN Preventive Medicine and Diagnosis Innovation Program, Wako, Saitama, Japan, Division of Genomic Technologies, RIKEN Center for Life Science Technologies, Yokohama, Japan, RIKEN Omics Science Center (OSC), Yokohama, Japan; RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa, Japan, Division of Genomic Technologies, RIKEN Center for Life Science Technologies, Yokohama, Japan, RIKEN Omics Science Center (OSC), Yokohama, Japan; RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa, Japan, Division of Genomic Technologies, RIKEN Center for Life Science Technologies, Yokohama, Japan, RIKEN Omics Science Center (OSC), Yokohama, Japan; RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa, Japan; RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa, Japan, Division of Genomic Technologies, RIKEN Center for Life Science Technologies, Yokohama, Japan, RIKEN Omics Science Center (OSC), Yokohama, Japan; RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa, Japan, Division of Genomic Technologies, RIKEN Center for Life Science Technologies, Yokohama, Japan; RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa, Japan, Division of Genomic Technologies, RIKEN Center for Life Science Technologies, Yokohama, Japan; RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa, Japan, Division of Genomic Technologies, RIKEN Center for Life Science Technologies, Yokohama, Japan, RIKEN Omics Science Center (OSC), Yokohama, Japan; RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa, Japan, Division of Genomic Technologies, RIKEN Center for Life Science Technologies, Yokohama, Japan, RIKEN Omics Science Center (OSC), Yokohama, Japan; RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa, Japan; Artificial Intelligence Research Center, AIST, Tokyo, Japan, Graduate School of Frontier Sciences, University of Tokyo, Chiba, Japan, AIST-Waseda University CBBD-OIL, AIST, Tokyo, Japan; Division of Genomic Technologies, RIKEN Center for Life Science Technologies, Yokohama, Japan; MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, United Kingdom; European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton, Cambridge, United Kingdom, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, United Kingdom; Computational Bioscience Research Centre, King Abdullah University of Science and Technology (KAUST), Thuwal, Saudi Arabia; Computational Bioscience Research Centre, King Abdullah University of Science and Technology (KAUST), Thuwal, Saudi Arabia; Department of Biochemistry, McGill University, Montral, Qubec, Canada; UNSW Centre for Vascular Research, University of New South Wales, Sydney, NSW, Australia; Harry Perkins Institute of Medical Research, and the Centre for Medical Research, University of Western Australia, QEII Medical Centre, Perth, WA, Australia; Department of Systems Biology, Columbia University Medical Center, Columbia University, New York, NY, United States; The Bioinformatics Centre, Department of Biology, University of Copenhagen, Copenhagen, Denmark, Biotech Research and Innovation Centre, University of Copenhagen, Copenhagen, Denmark; Division of Genomic Technologies, RIKEN Center for Life Science Technologies, Yokohama, Japan, RIKEN Omics Science Center (OSC), Yokohama, Japan; Department of Transfusion Medicine and Stem Cell Regulation, Juntendo University Graduate School of Medicine, Tokyo, Japan; Department of Statistics, University of California Berkeley, Berkeley, CA, United States; Computational Bioscience Research Centre, King Abdullah University of Science and Technology (KAUST), Thuwal, Saudi Arabia; The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Easter Bush, United Kingdom; Division of Genomic Technologies, RIKEN Center for Life Science Technologies, Yokohama, Japan, RIKEN Omics Science Center (OSC), Yokohama, Japan; Department of Medicine, Karolinska Institute at Karolinska University Hospital, Huddinge, Sweden; Graduate School of Frontier Sciences, University of Tokyo, Chiba, Japan, Artificial Intelligence Research Center (AIRC), National Institute of Advanced Industrial Science and Technology (AIST), Tokyo, Japan, Biotechnology Research Institute for Drug Discovery, National Institute of Advanced Industrial Science and Technology (AIST), Tokyo, Japan; Computational Bioscience Research Centre, King Abdullah University of Science and Technology (KAUST), Thuwal, Saudi Arabia; Department of Medicine, Karolinska Institute at Karolinska University Hospital, Huddinge, Sweden; Department of Dermatology and Allergy, Charit Campus Mitte, Universitatsmedizin Berlin, Berlin, Germany; The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Easter Bush, United Kingdom; Computational Bioscience Research Centre, King Abdullah University of Science and Technology (KAUST), Thuwal, Saudi Arabia; RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa, Japan; MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, United Kingdom; The Jackson Laboratory, Bar Harbor, ME, United States; The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Easter Bush, United Kingdom; Department of Systems Biology, Columbia University Medical Center, Columbia University, New York, NY, United States; Bioinformatics Institute, Agency for Science, Technology and Research (A*STAR), Singapore, Singapore; Department of Computer Science, Stanford University, Stanford, CA, United States; Australian Institute for Bioengineering and Nanotechnology (AIBN), University of Queensland, Brisbane St Lucia, QLD, Australia; Department of Medical and Biological Sciences, University of Udine, Udine, Italy; Department of Medical and Biological Sciences, University of Udine, Udine, Italy; Division of Genomic Technologies, RIKEN Center for Life Science Technologies, Yokohama, Japan, RIKEN Omics Science Center (OSC), Yokohama, Japan, Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore; Department of Statistics, University of California Berkeley, Berkeley, CA, United States, Department of Statistics, Oregon State University, Corvallis, OR, United States; Department of Statistics, University of California Berkeley, Berkeley, CA, United States; The Jackson Laboratory, Bar Harbor, ME, United States; McGill Centre for Bioinformatics and School of Computer Science, McGill University, Montral, Qubec, Canada; Genome Biology Unit, Istituto Nazionale di Genetica Molecolare (INGM) ‘Romeo and Enrica Invernizzi’, Milan, Italy; Division of Genomic Technologies, RIKEN Center for Life Science Technologies, Yokohama, Japan, RIKEN Omics Science Center (OSC), Yokohama, Japan; Database Center for Life Science, Research Organization of Information and Systems, Tokyo, Japan; The Bioinformatics Centre, Department of Biology, University of Copenhagen, Copenhagen, Denmark, Biotech Research and Innovation Centre, University of Copenhagen, Copenhagen, Denmark; Division of Genomic Technologies, RIKEN Center for Life Science Technologies, Yokohama, Japan; Computational Bioscience Research Centre, King Abdullah University of Science and Technology (KAUST), Thuwal, Saudi Arabia; The Bioinformatics Centre, Department of Biology, University of Copenhagen, Copenhagen, Denmark, Biotech Research and Innovation Centre, University of Copenhagen, Copenhagen, Denmark; Biozentrum, University of Basel, Basel, Switzerland, Swiss Institute of Bioinformatics, Basel, Switzerland; International Centre for Genetic Engineering and Biotechnology, Cape Town Component, Cape Town, South Africa, Division of Immunology, Institute of Infectious Diseases and Molecular Medicine, Health Science Faculty, University of Cape Town, Cape Town, South Africa; Department of Statistics, University of California Berkeley, Berkeley, CA, United States, Genomics Division, Lawrence Berkeley National Laboratory, Berkeley, CA, United States; The Jackson Laboratory, Bar Harbor, ME, United States; Division of Genomic Technologies, RIKEN Center for Life Science Technologies, Yokohama, Japan, RIKEN Omics Science Center (OSC), Yokohama, Japan, National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD, United States; The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Easter Bush, United Kingdom; RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa, Japan; Berlin Institute for Medical Systems Biology, Max-Delbruck Centre for Molecular Medicine, Berlin, Germany; Department of Systems Biology, Columbia University Medical Center, Columbia University, New York, NY, United States; McGill Centre for Bioinformatics and School of Computer Science, McGill University, Montral, Qubec, Canada; Biotechnology Center, Technische Universitat Dresden, Dresden, Germany; Sorbonne Universités, Université Pierre et Marie Curie, Laboratoire de Biologie Computationnelle et Quantitative, Paris, France; The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Easter Bush, United Kingdom; RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa, Japan, Division of Genomic Technologies, RIKEN Center for Life Science Technologies, Yokohama, Japan, RIKEN Omics Science Center (OSC), Yokohama, Japan; Telethon Kids Institute, The University of Western Australia, Subiaco, WA, Australia; Department of Medical and Biological Sciences, University of Udine, Udine, Italy; Division of Genomic Technologies, RIKEN Center for Life Science Technologies, Yokohama, Japan; Department of Medical Genetics, Centre for Molecular Medicine and Therapeutics, Child and Family Research Institute, University of British Columbia, Vancouver, BC, Canada, Graduate Program in Bioinformatics, University of British Columbia, Vancouver, BC, Canada; The Bioinformatics Centre, Department of Biology, University of Copenhagen, Copenhagen, Denmark, Biotech Research and Innovation Centre, University of Copenhagen, Copenhagen, Denmark; Fondazione Bruno Kessler, Trento, Italy; Children’s Hospital at Westmead, Sydney, NSW, Australia; Laboratorio Nazionale Consorzio Italiano Biotecnologie (LNCIB), Trieste, Italy; The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Easter Bush, United Kingdom; The Bioinformatics Centre, Department of Biology, University of Copenhagen, Copenhagen, Denmark, Department of Gastroenterology, Medical Section, Herlev Hospital, University of Copenhagen, Herlev, Denmark; The Bioinformatics Centre, Department of Biology, University of Copenhagen, Copenhagen, Denmark; Laboratorio Nazionale Consorzio Italiano Biotecnologie (LNCIB), Trieste, Italy; RIKEN Omics Science Center (OSC), Yokohama, Japan; Functional Genomics, Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, United States; Division of Genomic Technologies, RIKEN Center for Life Science Technologies, Yokohama, Japan, RIKEN Omics Science Center (OSC), Yokohama, Japan; Division of Genomic Technologies, RIKEN Center for Life Science Technologies, Yokohama, Japan, Centre for Integrative Bioinformatics (IBIVU), VU University Amsterdam, Amsterdam, Netherlands; Institute of Natural and Mathematical Sciences, Massey University Auckland, Albany, New Zealand; Ecole Polytechnique Fdrale de Lausanne and Swiss Institute of Bioinformatics, Lausanne, Switzerland; Institute of Pharmaceutical Sciences, Swiss Federal Institute of Technology, ETH Zurich, Zurich, Switzerland; Division of Genomic Technologies, RIKEN Center for Life Science Technologies, Yokohama, Japan, Institute of Fundamental Medicine and Biology, Kazan Federal University, Kazan, Russian Federation; Telethon Institute of Genetics and Medicine (TIGEM), Pozzuoli, Italy; Department of Neurology, University at Buffalo School of Medicine and Biomedical Sciences, Buffalo, NY, United States; Institute of Pharmaceutical Sciences, Swiss Federal Institute of Technology, ETH Zurich, Zurich, Switzerland; Department of Biostatistics, Harvard School of Public Health, Boston, MA, United States; Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Barcelona, Spain; RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa, Japan, Department of Gastroenterology, Research Center for Hepatitis and Immunology, Research Institute, National Center for Global Health and Medicine, Chiba, Japan; Department of Biochemistry, McGill University, Montral, Qubec, Canada; Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway; Department of Otology and Laryngology, Harvard Medical School, Boston, MA, United States; Department of Internal Medicine III, University Hospital Regensburg, Regensburg, Germany, Regensburg Centre for Interventional Immunology (RCI), Regensburg, Germany; Department of Medicine, Karolinska Institute at Karolinska University Hospital, Huddinge, Sweden; Department of Biosciences and Nutrition, Karolinska Institute, Stockholm, Sweden; Department of Biochemistry and Biophysics, Stockholm University, Stockholm, Sweden; RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa, Japan; Division of Neural Differentiation and Regeneration, Kobe University Graduate School of Medicine, Kobe, Japan; Division of Genomic Technologies, RIKEN Center for Life Science Technologies, Yokohama, Japan; Department of Psychiatry and Behavioral Sciences, University of Miami Miller School of Medicine, Miami, FL, United States; F.M. Kirby Neurobiology Center, Department of Neurology, Boston Children’s Hospital, Harvard Medical School, Boston, MA, United States; Department of Otology and Laryngology, Harvard Medical School, Boston, MA, United States, Department of Biological Sciences, University of Delaware, Newark, DE, United States, Department of Biochemistry and Cell Biology, Rice University, Houston, TX, United States, Department of Bioengineering, Rice University, Houston, TX, United States; Mater Research Institute, and Queensland Brain Institute, University of Queensland, Brisbane, QLD, Australia; Vavilov Institute of General Genetics, Russian Academy of Sciences, Moscow, Russian Federation, Department of Oncology, Division of Biostatistics and Bioinformatics, Johns Hopkins University School of Medicine, Baltimore, MD, United States; Berlin Institute for Medical Systems Biology, Max-Delbruck Centre for Molecular Medicine, Berlin, Germany; Berlin Institute for Medical Systems Biology, Max-Delbruck Centre for Molecular Medicine, Berlin, Germany, Genome Function Group, MRC Clinical Sciences Centre, Imperial College London, London, United Kingdom; Division of Genomic Technologies, RIKEN Center for Life Science Technologies, Yokohama, Japan, Harry Perkins Institute of Medical Research, and the Centre for Medical Research, University of Western Australia, QEII Medical Centre, Perth, WA, Australia, RIKEN Omics Science Center (OSC), Yokohama, Japan; The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Easter Bush, United Kingdom; Science for Life Laboratory, KTH-Royal Institute of Technology, Stockholm, Sweden; Division of Genomic Technologies, RIKEN Center for Life Science Technologies, Yokohama, Japan, RIKEN Omics Science Center (OSC), Yokohama, Japan; Fondazione Bruno Kessler, Trento, Italy; The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Easter Bush, United Kingdom; Artificial Intelligence Research Center (AIRC), National Institute of Advanced Industrial Science and Technology (AIST), Tokyo, Japan, Department of Computational Biology and Medical Sciences, University of Tokyo, Tokyo, Japan; RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa, Japan; Research Institute for Diseases of Old Age, Juntendo University Graduate School of Medicine, Tokyo, Japan; Fondazione Bruno Kessler, Trento, Italy; Division of Genomic Technologies, RIKEN Center for Life Science Technologies, Yokohama, Japan, RIKEN Omics Science Center (OSC), Yokohama, Japan; RIKEN Quantitative Biology Center, Suita, Japan, Graduate School of Information Science and Technology, Osaka University, Suita, Japan; Department of Biosciences and Nutrition, Karolinska Institute, Stockholm, Sweden; The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Easter Bush, United Kingdom; Department of Internal Medicine III, University Hospital Regensburg, Regensburg, Germany, Regensburg Centre for Interventional Immunology (RCI), Regensburg, Germany; Department of Biomedicine, Bioinformatics Core Facility, University Hospital Basel, Basel, Switzerland; Academic Medical Center, University of Amsterdam, Amsterdam, Netherlands; RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa, Japan, The Systems Biology Institute, Tokyo, Japan; Division of Biological and Environmental Sciences & Engineering, King Abdullah University of Science and Technology (KAUST), Thuwal, Saudi Arabia; Functional Genomics, Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, United States; Computational Bioscience Research Centre, King Abdullah University of Science and Technology (KAUST), Thuwal, Saudi Arabia, Division of Biological and Environmental Sciences & Engineering, King Abdullah University of Science and Technology (KAUST), Thuwal, Saudi Arabia; Department for Bioinformatics and Computational Biology, Technische UniversitŁt Mnchen, Garching, Germany; Department of Medical Genetics, Centre for Molecular Medicine and Therapeutics, Child and Family Research Institute, University of British Columbia, Vancouver, BC, Canada; Department of Computer Science, University of Bristol, Bristol, United Kingdom; Institute of Biotechnology, University of Helsinki, Helsinki, Finland; Biozentrum, University of Basel, Basel, Switzerland, Swiss Institute of Bioinformatics, Basel, Switzerland; Department of Dermatology and Allergy, Charit Campus Mitte, Universitatsmedizin Berlin, Berlin, Germany; Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Barcelona, Spain; International Centre for Genetic Engineering and Biotechnology, Cape Town Component, Cape Town, South Africa, Division of Immunology, Institute of Infectious Diseases and Molecular Medicine, Health Science Faculty, University of Cape Town, Cape Town, South Africa; RIKEN Preventive Medicine and Diagnosis Innovation Program, Wako, Saitama, Japan, Division of Genomic Technologies, RIKEN Center for Life Science Technologies, Yokohama, Japan, Institute of Fundamental Medicine and Biology, Kazan Federal University, Kazan, Russian Federation; Area of Neuroscience, International School for Advanced Studies (SISSA), Trieste, Italy, Department of Neuroscience and Brain Technologies, Italian Institute of Technologies (IIT), Genoa, Italy; Department of Medical Genetics, Centre for Molecular Medicine and Therapeutics, Child and Family Research Institute, University of British Columbia, Vancouver, BC, Canada; Faculty of Medicine, Imperial College London, London, United Kingdom, Department of Biology, University of Bergen, Bergen, Norway; The Jackson Laboratory, Bar Harbor, ME, United States; Science for Life Laboratory, KTH-Royal Institute of Technology, Stockholm, Sweden, Department of Proteomics, KTH-Royal Institute of Technology, Stockholm, Sweden; Graduate School of Frontier Sciences, University of Tokyo, Chiba, Japan, Artificial Intelligence Research Center (AIRC), National Institute of Advanced Industrial Science and Technology (AIST), Tokyo, Japan, Department of Electrical Engineering and Bioscience, Faculty of Science and Engineering, Waseda University, Tokyo, Japan; Division of Genomic Technologies, RIKEN Center for Life Science Technologies, Yokohama, Japan; RIKEN Center for Life Science Technologies, Division of Bio-Function Dynamics Imaging, Kobe, Japan; Division of Genomic Technologies, RIKEN Center for Life Science Technologies, Yokohama, Japan, RIKEN Omics Science Center (OSC), Yokohama, Japan; Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, United Kingdom; Division of Genomic Technologies, RIKEN Center for Life Science Technologies, Yokohama, Japan, RIKEN Omics Science Center (OSC), Yokohama, Japan; RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa, Japan; Division of Genomic Technologies, RIKEN Center for Life Science Technologies, Yokohama, Japan, RIKEN Omics Science Center (OSC), Yokohama, Japan; Department of Neurology, Juntendo University Graduate School of Medicine, Tokyo, Japan; Research Institute for Diseases of Old Age, Juntendo University Graduate School of Medicine, Tokyo, Japan, Department of Neurology, Juntendo University Graduate School of Medicine, Tokyo, Japan, Department of Treatment and Research in Multiple Sclerosis and Neuro-intractable Disease, Juntendo University Graduate School of Medicine, Tokyo, Japan, Department of Research for Parkinsons Disease, Juntendo University Graduate School of Medicine, Tokyo, Japan; Department of Stem Cells and Applied Medicine, Osaka University Graduate School of Medicine, Suita, Japan, Department of Ophthalmology, Osaka University Graduate School of Medicine, Suita, Japan; Melanoma Research Center, The Wistar Institute, Philadelphia, PA, United States; Department of Human Genetics, Leiden University Medical Center, Leiden, Netherlands; German Center for Neurodegenerative Diseases (DZNE), Tubingen, Germany; Department of Biostatistics, Harvard School of Public Health, Boston, MA, United States, Sheffield Institute for Translational Neuroscience, University of Sheffield, Sheffield, United Kingdom; Australian Infectious Diseases Research Centre (AID), University of Queensland, Brisbane, QLD, Australia; Department of Biostatistics, Harvard School of Public Health, Boston, MA, United States; Department of Human Genetics, Leiden University Medical Center, Leiden, Netherlands; Division of Genomic Technologies, RIKEN Center for Life Science Technologies, Yokohama, Japan; Division of Genomic Technologies, RIKEN Center for Life Science Technologies, Yokohama, Japan, RIKEN Omics Science Center (OSC), Yokohama, Japan; Department of Respiratory Medicine, Graduate School of Medicine, University of Tokyo, Tokyo, Japan; Molecular Profiling Research Center for Drug Discovery, National Institute of Advanced Industrial Science and Technology (AIST), Tokyo, Japan; Graduate School of Frontier Sciences, University of Tokyo, Chiba, Japan, Artificial Intelligence Research Center (AIRC), National Institute of Advanced Industrial Science and Technology (AIST), Tokyo, Japan, Computational Biology Research Center, National Institute of Advanced Industrial Science and Technology (AIST), Tokyo, Japan; Harry Perkins Institute of Medical Research, and the Centre for Medical Research, University of Western Australia, QEII Medical Centre, Perth, WA, Australia; The University of Melbourne Centre for Stem Cell Systems, School of Biomedical Sciences, The University of Melbourne, Victoria, Australia, Walter and Eliza Hall Institute of Medical Research, Melbourne, VIC, Australia; Division of Genomic Technologies, RIKEN Center for Life Science Technologies, Yokohama, Japan; Sorbonne Universités, Université Pierre et Marie Curie, Laboratoire de Biologie Computationnelle et Quantitative, Paris, France; The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Easter Bush, United Kingdom; The Bioinformatics Centre, Department of Biology, University of Copenhagen, Copenhagen, Denmark, Biotech Research and Innovation Centre, University of Copenhagen, Copenhagen, Denmark; RIKEN Bioinformatics and Systems Engineering Division (BASE), Yokohama, Japan, Medical Research Support Center, Kyoto University Graduate School of Medicine, Kyoto, Japan; RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa, Japan; Department of Bioscience, Nagahama Institute of Bio-Science and Technology, Nagahama, Japan; Center for Information Biology and DNA Data Bank of Japan, National Institute of Genetics, Mishima, Japan; RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa, Japan; Division of Genomic Technologies, RIKEN Center for Life Science Technologies, Yokohama, Japan, RIKEN Omics Science Center (OSC), Yokohama, Japan; RIKEN Preventive Medicine and Diagnosis Innovation Program, Wako, Saitama, Japan; Bioinformatics Institute, Agency for Science, Technology and Research (A*STAR), Singapore, Singapore; Division of Biological and Environmental Sciences & Engineering, King Abdullah University of Science and Technology (KAUST), Thuwal, Saudi Arabia; Bioinformatics Institute, Agency for Science, Technology and Research (A*STAR), Singapore, Singapore; Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Barcelona, Spain; The Bioinformatics Centre, Department of Biology, University of Copenhagen, Copenhagen, Denmark, Biotech Research and Innovation Centre, University of Copenhagen, Copenhagen, Denmark; Biozentrum, University of Basel, Basel, Switzerland, Swiss Institute of Bioinformatics, Basel, Switzerland; The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Easter Bush, United Kingdom; Fondazione Bruno Kessler, Trento, Italy; Division of Genomic Technologies, RIKEN Center for Life Science Technologies, Yokohama, Japan, RIKEN Omics Science Center (OSC), Yokohama, Japan; Laboratory Animal Research Center, Institute of Medical Science, University of Tokyo, Tokyo, Japan; Division of Genomic Technologies, RIKEN Center for Life Science Technologies, Yokohama, Japan, RIKEN Omics Science Center (OSC), Yokohama, Japan; Division of Genomic Technologies, RIKEN Center for Life Science Technologies, Yokohama, Japan, RIKEN Omics Science Center (OSC), Yokohama, Japan; Department of Human Genetics, Leiden University Medical Center, Leiden, Netherlands; Center for Information Biology and DNA Data Bank of Japan, National Institute of Genetics, Mishima, Japan; RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa, Japan; Department of Obstetrics and Gynecology, Juntendo University, Tokyo, Japan; Institute of Genomics, School of Biomedical Sciences, Huaqiao University, Xiamen, China, St. Laurent Institute, Woburn, MA, United States; Vavilov Institute of General Genetics, Russian Academy of Sciences, Moscow, Russian Federation, A.N. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow, Russian Federation; Database Center for Life Science, Research Organization of Information and Systems, Tokyo, Japan; Division of Genomic Technologies, RIKEN Center for Life Science Technologies, Yokohama, Japan, RIKEN Omics Science Center (OSC), Yokohama, Japan; RIKEN Bioinformatics and Systems Engineering Division (BASE), Yokohama, Japan; RIKEN Preventive Medicine and Diagnosis Innovation Program, Wako, Saitama, Japan, RIKEN Omics Science Center (OSC), Yokohama, Japan; RIKEN Preventive Medicine and Diagnosis Innovation Program, Wako, Saitama, Japan, Division of Genomic Technologies, RIKEN Center for Life Science Technologies, Yokohama, Japan, RIKEN Omics Science Center (OSC), Yokohama, Japan; RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa, Japan; Department of Gastroenterology, Research Center for Hepatitis and Immunology, Research Institute, National Center for Global Health and Medicine, Chiba, Japan; Department of Ophthalmology, Kyoto Prefectural University of Medicine, Kyoto, Japan; Division of Genomic Technologies, RIKEN Center for Life Science Technologies, Yokohama, Japan, RIKEN Omics Science Center (OSC), Yokohama, Japan; Department of Otology and Laryngology, Harvard Medical School, Boston, MA, United States; Diamantina Institute, University of Queensland, Brisbane St Lucia, QLD, Australia; Department of Biosciences and Nutrition, Karolinska Institute, Stockholm, Sweden, Folkhalsan Institute of Genetics, Helsinki, Finland, Science for Life Laboratory, Karolinska Institute, Solna, Sweden; UNSW Centre for Vascular Research, University of New South Wales, Sydney, NSW, Australia; Department of Computational Biology, Faculty of Frontier Sciences, University of Tokyo, Chiba, Japan; Division of Genomic Technologies, RIKEN Center for Life Science Technologies, Yokohama, Japan, RIKEN Omics Science Center (OSC), Yokohama, Japan; RIKEN Center for Developmental Biology, Kobe, Japan; Division of Cellular Therapy, Institute of Medical Science, University of Tokyo, Tokyo, Japan, Division of Stem Cell Signaling, Institute of Medical Science, University of Tokyo, Tokyo, Japan; RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa, Japan, The Systems Biology Institute, Tokyo, Japan, Sony Computer Science Laboratories, Inc, Tokyo, Japan, Systems Biology Institute (SBI) Australia, Monash University, Clayton, VIC, Australia, Okinawa Institute of Science and Technology, Onna, Japan; Laboratorio Nazionale Consorzio Italiano Biotecnologie (LNCIB), Trieste, Italy; Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway; Harry Perkins Institute of Medical Research, and the Centre for Medical Research, University of Western Australia, QEII Medical Centre, Perth, WA, Australia; Department for Bioinformatics and Computational Biology, Technische UniversitŁt Mnchen, Garching, Germany; Department of Respiratory Medicine and Nottingham Respiratory Research Unit, University of Nottingham, Nottingham, United Kingdom; Center for Information Biology and DNA Data Bank of Japan, National Institute of Genetics, Mishima, Japan; RIKEN Preventive Medicine and Diagnosis Innovation Program, Wako, Saitama, Japan; Division of Genomic Technologies, RIKEN Center for Life Science Technologies, Yokohama, Japan, RIKEN Omics Science Center (OSC), Yokohama, Japan; RIKEN Center for Life Science Technologies, Division of Bio-Function Dynamics Imaging, Kobe, Japan; Department of Hematology, Juntendo University Graduate School of Medicine, Tokyo, Japan; Department of Coloproctological Surgery, Faculty of Medicine, Juntendo University School of Medicine, Tokyo, Japan; Division of Genomic Technologies, RIKEN Center for Life Science Technologies, Yokohama, Japan, RIKEN Omics Science Center (OSC), Yokohama, Japan; RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa, Japan; RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa, Japan, Department of Microbiology and Immunology, Keio University School of Medicine, Tokyo, Japan; Division of Genomic Technologies, RIKEN Center for Life Science Technologies, Yokohama, Japan, RIKEN Omics Science Center (OSC), Yokohama, Japan; Berlin Institute for Medical Systems Biology, Max-Delbruck Centre for Molecular Medicine, Berlin, Germany; Vavilov Institute of General Genetics, Russian Academy of Sciences, Moscow, Russian Federation, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russian Federation, Skolkovo Institute of Science and Technology, Moscow, Russian Federation; Department of Computer Science, Stanford University, Stanford, CA, United States, Department of Genetics, Stanford University, Stanford, CA, United States; Department of Ophthalmology and Visual Science, Tohoku University Graduate School of Medicine, Sendai, Japan, Department of Retinal Disease Control, Tohoku University Graduate School of Medicine, Sendai, Japan; The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Easter Bush, United Kingdom; Artificial Intelligence Research Center (AIRC), National Institute of Advanced Industrial Science and Technology (AIST), Tokyo, Japan; RIKEN Center for Life Science Technologies, Division of Bio-Function Dynamics Imaging, Kobe, Japan; Bioinformatics Institute, Agency for Science, Technology and Research (A*STAR), Singapore, Singapore; Division of Genomic Technologies, RIKEN Center for Life Science Technologies, Yokohama, Japan, RIKEN Omics Science Center (OSC), Yokohama, Japan; Department of Medical Genetics, Centre for Molecular Medicine and Therapeutics, Child and Family Research Institute, University of British Columbia, Vancouver, BC, Canada; Division of Genomic Technologies, RIKEN Center for Life Science Technologies, Yokohama, Japan, RIKEN Omics Science Center (OSC), Yokohama, Japan, Telethon Kids Institute, The University of Western Australia, Subiaco, WA, Australia; The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Easter Bush, United Kingdom; Diamantina Institute, University of Queensland, Brisbane St Lucia, QLD, Australia; Institut de Biologie Computationnelle, Montpellier, France, Institut de Génétique Moléculaire de Montpellier, University of Montpellier, CNRS, Montpellier, France, LIRMM, Univ Montpellier, CNRS, Montpellier, France, Department of Medical Genetics, Centre for Molecular Medicine and Therapeutics, Child and Family Research Institute, University of British Columbia, Vancouver, BC, Canada, Institute of Molecular Genetics of Montpellier, Montpellier, France; Department of Dermatology, Kyungpook National University School of Medicine, Daegu, South Korea; Faculty of Medicine, Imperial College London, London, United Kingdom; Department of Biosciences and Nutrition, Karolinska Institute, Stockholm, Sweden; The Bioinformatics Centre, Department of Biology, University of Copenhagen, Copenhagen, Denmark, Biotech Research and Innovation Centre, University of Copenhagen, Copenhagen, Denmark, Department of Mathematical Sciences, University of Copenhagen, Copenhagen, Denmark; Harry Perkins Institute of Medical Research, and the Centre for Medical Research, University of Western Australia, QEII Medical Centre, Perth, WA, Australia; The Bioinformatics Centre, Department of Biology, University of Copenhagen, Copenhagen, Denmark, Biotech Research and Innovation Centre, University of Copenhagen, Copenhagen, Denmark; Center for Molecular Medicine and Genetics, Wayne State University, Detroit, MI, United States, Department of Neurology, School of Medicine, Wayne State University, Detroit, MI, United States; Division of Genomic Technologies, RIKEN Center for Life Science Technologies, Yokohama, Japan, RIKEN Omics Science Center (OSC), Yokohama, Japan; Department of Systems Biology, Columbia University Medical Center, Columbia University, New York, NY, United States; RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa, Japan; Department of Medical Genetics, Centre for Molecular Medicine and Therapeutics, Child and Family Research Institute, University of British Columbia, Vancouver, BC, Canada; Vavilov Institute of General Genetics, Russian Academy of Sciences, Moscow, Russian Federation, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russian Federation, Department of Medical and Biological Physics, Moscow Institute of Physics and Technology, Moscow, Russian Federation; Division of Genomic Technologies, RIKEN Center for Life Science Technologies, Yokohama, Japan, RIKEN Omics Science Center (OSC), Yokohama, Japan; RIKEN Center for Developmental Biology, Kobe, Japan; Department of Systems and Computational Biology, Albert Einstein College of Medicine, New York, NY, United States; Department of Ophthalmology and Visual Science, Tohoku University Graduate School of Medicine, Sendai, Japan; Division of Genomic Technologies, RIKEN Center for Life Science Technologies, Yokohama, Japan; Australian Institute for Bioengineering and Nanotechnology (AIBN), University of Queensland, Brisbane St Lucia, QLD, Australia; Department of Medical Genetics, Centre for Molecular Medicine and Therapeutics, Child and Family Research Institute, University of British Columbia, Vancouver, BC, Canada; Graduate School of Information Science and Technology, Osaka University, Suita, Japan; Vavilov Institute of General Genetics, Russian Academy of Sciences, Moscow, Russian Federation, IMPPC, Institute of Predictive and Personalized Medicine of Cancer, Badalona, Spain, Institute of Bioengineering, Research Center of Biotechnology, Moscow, Russian Federation; European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton, Cambridge, United Kingdom; Department of Medicine, Karolinska Institute at Karolinska University Hospital, Huddinge, Sweden; MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, United Kingdom; Immunology Frontier Research Center, Osaka University, Suita, Japan; Division of Genomic Technologies, RIKEN Center for Life Science Technologies, Yokohama, Japan; Department of Biochemistry, McGill University, Montral, Qubec, Canada, RIKEN Center for Developmental Biology, Kobe, Japan; Kanagawa Cancer Center Research Institute, Yokohama, Japan; RIKEN Brain Science Institute, Saitama, Japan; Research Center for Genomic Medicine, Saitama Medical University, Saitama, Japan; Immunology Frontier Research Center, Osaka University, Suita, Japan; RIKEN Center for Developmental Biology, Kobe, Japan; RIKEN Preventive Medicine and Diagnosis Innovation Program, Wako, Saitama, Japan; Department of Transfusion Medicine and Stem Cell Regulation, Juntendo University Graduate School of Medicine, Tokyo, Japan; RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa, Japan, Department of Medical Life Science, Graduate School of Medical Life Science, Yokohama City University, Yokohama, Japan; Division of Genomic Technologies, RIKEN Center for Life Science Technologies, Yokohama, Japan, RIKEN Omics Science Center (OSC), Yokohama, Japan; Department of Gene Expression Regulation, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan; Department of Biosciences and Nutrition, Karolinska Institute, Stockholm, Sweden; Department of Anatomy and Embryology, Leiden University Medical Center, Leiden, Netherlands; Genomics Division, Lawrence Berkeley National Laboratory, Berkeley, CA, United States; RIKEN Preventive Medicine and Diagnosis Innovation Program, Wako, Saitama, Japan, Division of Genomic Technologies, RIKEN Center for Life Science Technologies, Yokohama, Japan; Research Center for Genomic Medicine, Saitama Medical University, Saitama, Japan; Department of Obstetrics and Gynecology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan; Department of Respiratory Medicine, Graduate School of Medicine, University of Tokyo, Tokyo, Japan; Research Center for Genomic Medicine, Saitama Medical University, Saitama, Japan; Division of Cellular Therapy, Institute of Medical Science, University of Tokyo, Tokyo, Japan, Division of Stem Cell Signaling, Institute of Medical Science, University of Tokyo, Tokyo, Japan; Human Genome Center, The Institute of Medical Science, University of Tokyo, Tokyo, Japan; Division of Genomic Technologies, RIKEN Center for Life Science Technologies, Yokohama, Japan; Center for Information Biology and DNA Data Bank of Japan, National Institute of Genetics, Mishima, Japan; RIKEN BioResource Center, Tsukuba, Japan; Department of Ophthalmology and Visual Science, Tohoku University Graduate School of Medicine, Sendai, Japan, Department of Retinal Disease Control, Tohoku University Graduate School of Medicine, Sendai, Japan, Department of Advanced Ophthalmic Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan; School of Mathematics, University of Bristol, Bristol, United Kingdom; Department of Biology, University of Bergen, Bergen, Norway, Department of Informatics, University of Bergen, Bergen, Norway; Division of Genomic Technologies, RIKEN Center for Life Science Technologies, Yokohama, Japan; Australian Institute for Bioengineering and Nanotechnology (AIBN), University of Queensland, Brisbane St Lucia, QLD, Australia; Department of Ophthalmology, Osaka University Graduate School of Medicine, Suita, Japan; Department of Ophthalmology and Visual Science, Tohoku University Graduate School of Medicine, Sendai, Japan; Division of Genomic Technologies, RIKEN Center for Life Science Technologies, Yokohama, Japan, RIKEN Omics Science Center (OSC), Yokohama, Japan; Division of Genomic Technologies, RIKEN Center for Life Science Technologies, Yokohama, Japan; Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Barcelona, Spain; Tohoku Medical Megabank Organization, Tohoku University, Sendai, Japan; Immunology Frontier Research Center, Osaka University, Suita, Japan, Department of Frontier Research in Tumor Immunology, Center of Medical Innovation and Translational Research, Osaka University, Osaka, Japan; RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa, Japan; Department of Biochemistry, Ohu University School of Pharmaceutical Sciences, Koriyama, Japan; Kanagawa Cancer Center Research Institute, Yokohama, Japan; RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa, Japan, Immunology Frontier Research Center, Osaka University, Suita, Japan, Department of Statistical Genetics, Osaka University Graduate School of Medicine, Suita, Japan; RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa, Japan, Institute for Protein Research, Osaka University, Suita, Japan; Division of Genomic Technologies, RIKEN Center for Life Science Technologies, Yokohama, Japan, Research Center for Genomic Medicine, Saitama Medical University, Saitama, Japan; Science for Life Laboratory, KTH-Royal Institute of Technology, Stockholm, Sweden; Division of Biological and Environmental Sciences & Engineering, King Abdullah University of Science and Technology (KAUST), Thuwal, Saudi Arabia, Dulbecco Telethon Institute at IRCSS Fondazione Santa Lucia, Rome, Italy; Bioinformatics Institute, Agency for Science, Technology and Research (A*STAR), Singapore, Singapore; International Centre for Genetic Engineering and Biotechnology, Cape Town Component, Cape Town, South Africa, Division of Immunology, Institute of Infectious Diseases and Molecular Medicine, Health Science Faculty, University of Cape Town, Cape Town, South Africa; Biozentrum, University of Basel, Basel, Switzerland, Swiss Institute of Bioinformatics, Basel, Switzerland; Dulbecco Telethon Institute at IRCSS Fondazione Santa Lucia, Rome, Italy; International Centre for Genetic Engineering and Biotechnology, Cape Town Component, Cape Town, South Africa, Division of Immunology, Institute of Infectious Diseases and Molecular Medicine, Health Science Faculty, University of Cape Town, Cape Town, South Africa; Human Genome Center, The Institute of Medical Science, University of Tokyo, Tokyo, Japan; Division of Genomic Technologies, RIKEN Center for Life Science Technologies, Yokohama, Japan, RIKEN Omics Science Center (OSC), Yokohama, Japan; Department of Anatomy and Embryology, Leiden University Medical Center, Leiden, Netherlands; Division of Oncology and Pathology, Department of Clinical Sciences, Lund University, Lund, Sweden; Department of Immunobiology, Biomedical Primate Research Centre, Rijswijk, Netherlands; Laboratorio Nazionale Consorzio Italiano Biotecnologie (LNCIB), Trieste, Italy; Division of Genomic Technologies, RIKEN Center for Life Science Technologies, Yokohama, Japan, RIKEN Omics Science Center (OSC), Yokohama, Japan; Berlin Institute for Medical Systems Biology, Max-Delbruck Centre for Molecular Medicine, Berlin, Germany, Genome Function Group, MRC Clinical Sciences Centre, Imperial College London, London, United Kingdom; Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden, Science for Life Laboratory, Uppsala University, Uppsala, Sweden; Division of Genomic Technologies, RIKEN Center for Life Science Technologies, Yokohama, Japan; Artificial Intelligence Research Center (AIRC), National Institute of Advanced Industrial Science and Technology (AIST), Tokyo, Japan; Department of BioSciences, Rice University, Houston, TX, United States, Center for Translational Cancer Research, Helen F. Graham Cancer Center & Research Institute, Newark, DE, United States, Department of Biomedical Engineering, University of Delaware, Newark, DE, United States; Dulbecco Telethon Institute at IRCSS Fondazione Santa Lucia, Rome, Italy; The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Easter Bush, United Kingdom; RIKEN Center for Life Science Technologies, Division of Bio-Function Dynamics Imaging, Kobe, Japan; Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, United States, Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, United States; Department of Computer Science, University of Bristol, Bristol, United Kingdom, Program in Cardiovascular and Metabolic Disorders, DukeNUS Medical School, Singapore, Singapore; Division of Biological and Environmental Sciences & Engineering, King Abdullah University of Science and Technology (KAUST), Thuwal, Saudi Arabia; Department of Internal Medicine III, University Hospital Regensburg, Regensburg, Germany, Regensburg Centre for Interventional Immunology (RCI), Regensburg, Germany; The Bioinformatics Centre, Department of Biology, University of Copenhagen, Copenhagen, Denmark; Berlin Institute for Medical Systems Biology, Max-Delbruck Centre for Molecular Medicine, Berlin, Germany; German Center for Neurodegenerative Diseases (DZNE), Tubingen, Germany; The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Easter Bush, United Kingdom; Department of Human Genetics, Leiden University Medical Center, Leiden, Netherlands; Department for Bioinformatics and Computational Biology, Technische UniversitŁt Mnchen, Garching, Germany; Institute of Pharmaceutical Sciences, Swiss Federal Institute of Technology, ETH Zurich, Zurich, Switzerland; Harry Perkins Institute of Medical Research, and the Centre for Medical Research, University of Western Australia, QEII Medical Centre, Perth, WA, Australia; Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway; Department of Biochemistry and Biophysics, Stockholm University, Stockholm, Sweden; Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway, Department of Computer and Information Science, Norwegian University of Science and Technology, Trondheim, Norway; Division of Breast Oncology, Juntendo University School of Medicine, Tokyo, Japan; Department of Neurology, Juntendo University Graduate School of Medicine, Tokyo, Japan; Division of Breast Oncology, Juntendo University School of Medicine, Tokyo, Japan; Department of Respiratory Medicine, Graduate School of Medicine, University of Tokyo, Tokyo, Japan, Division for Health Service Promotion, University of Tokyo, Tokyo, Japan; Immunology Frontier Research Center, Osaka University, Suita, Japan, Department of Experimental Pathology, Institute for Frontier Medical Sciences, Kyoto University, Kyoto, Japan; Division of Genomic Technologies, RIKEN Center for Life Science Technologies, Yokohama, Japan, RIKEN Omics Science Center (OSC), Yokohama, Japan; RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa, Japan, Department of Statistical Genetics, Osaka University Graduate School of Medicine, Suita, Japan, Department of Allergy and Rheumatology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan; RIKEN Brain Science Institute, Saitama, Japan; The Bioinformatics Centre, Department of Biology, University of Copenhagen, Copenhagen, Denmark, Biotech Research and Innovation Centre, University of Copenhagen, Copenhagen, Denmark; Division of Genomic Technologies, RIKEN Center for Life Science Technologies, Yokohama, Japan, RIKEN Omics Science Center (OSC), Yokohama, Japan; Department of Ophthalmology, Osaka University Graduate School of Medicine, Suita, Japan; Laboratory Animal Research Center, Institute of Medical Science, University of Tokyo, Tokyo, Japan; RIKEN Omics Science Center (OSC), Yokohama, Japan, Biomedical Research Centre at Guy’s and St Thomas’ Trust, Genomics Core Facility, Guy’s Hospital, London, United Kingdom; Division of Gene Regulation, Institute for Advanced Medical Research, Keio University School of Medicine, Tokyo, Japan; Department of Informatics, Technische UniversitŁt Mnchen, Garching, Germany; Institute of Natural and Mathematical Sciences, Massey University Auckland, Albany, New Zealand; Department of Internal Medicine III, University Hospital Regensburg, Regensburg, Germany; Biozentrum, University of Basel, Basel, Switzerland, Swiss Institute of Bioinformatics, Basel, Switzerland; Department of Medical and Biological Sciences, University of Udine, Udine, Italy, Laboratorio Nazionale Consorzio Italiano Biotecnologie (LNCIB), Trieste, Italy; Berlin Institute for Medical Systems Biology, Max-Delbruck Centre for Molecular Medicine, Berlin, Germany; Department of Human Genetics, Leiden University Medical Center, Leiden, Netherlands; Paracelsus Medical University, Institute of Anatomy, Nuremberg, Germany; MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, United Kingdom; Graduate School of Information Science and Technology, Osaka University, Suita, Japan; RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa, Japan; Artificial Intelligence Research Center (AIRC), National Institute of Advanced Industrial Science and Technology (AIST), Tokyo, Japan, Department of Computer Science, Tokyo Institute of Technology, Tokyo, Japan; RIKEN Center for Developmental Biology, Kobe, Japan, International Research Center for Medical Sciences, Kumamoto University, Kumamoto, Japan; Department of Biostatistics, Harvard School of Public Health, Boston, MA, United States; Department of Systems Biology, Columbia University Medical Center, Columbia University, New York, NY, United States, Department of Neurology and Center for Translational Systems Biology, Mount Sinai School of Medicine, New York, NY, United States; Division of Genomic Technologies, RIKEN Center for Life Science Technologies, Yokohama, Japan, RIKEN Omics Science Center (OSC), Yokohama, Japan; German Center for Neurodegenerative Diseases (DZNE), Tubingen, Germany; Science for Life Laboratory, KTH-Royal Institute of Technology, Stockholm, Sweden; Science for Life Laboratory, KTH-Royal Institute of Technology, Stockholm, Sweden, Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden; Department of Biosciences and Nutrition, Karolinska Institute, Stockholm, Sweden; III, St. Laurent Institute, Woburn, MA, United States, Department of Molecular Biology, Cell Biology, and Biochemistry, Brown University, Providence, RI, United States; Department of Statistics, University of California Berkeley, Berkeley, CA, United States, Genomics Division, Lawrence Berkeley National Laboratory, Berkeley, CA, United States; Department of Research and Development of Next Generation Medicine, Faculty of Medical Sciences, Kyushu University, Fukuoka, Japan; The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Easter Bush, United Kingdom; Division of Genomic Technologies, RIKEN Center for Life Science Technologies, Yokohama, Japan, RIKEN Omics Science Center (OSC), Yokohama, Japan; Department of General Thoracic Surgery, Juntendo University School of Medicine, Tokyo, Japan; Center for Radioisotope Sciences, Tohoku University Graduate School of Medicine, Sendai, Japan; Division of Genomic Technologies, RIKEN Center for Life Science Technologies, Yokohama, Japan, RIKEN Omics Science Center (OSC), Yokohama, Japan; Division of Genomic Technologies, RIKEN Center for Life Science Technologies, Yokohama, Japan, RIKEN Omics Science Center (OSC), Yokohama, Japan; Department of Medical Genetics, Centre for Molecular Medicine and Therapeutics, Child and Family Research Institute, University of British Columbia, Vancouver, BC, Canada; Melanoma Research Center, The Wistar Institute, Philadelphia, PA, United States; Department of Obstetrics and Gynecology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan; Division of Genomic Technologies, RIKEN Center for Life Science Technologies, Yokohama, Japan, RIKEN Omics Science Center (OSC), Yokohama, Japan; RIKEN Center for Developmental Biology, Kobe, Japan; Department of General Thoracic Surgery, Juntendo University School of Medicine, Tokyo, Japan; Department of Obstetrics and Gynecology, Juntendo University, Tokyo, Japan; Graduate School of Information Science and Technology, Osaka University, Suita, Japan; Harry Perkins Institute of Medical Research, and the Centre for Medical Research, University of Western Australia, QEII Medical Centre, Perth, WA, Australia; Tohoku Medical Megabank Organization, Tohoku University, Sendai, Japan, Department of Systems Biology, Graduate School of Biochemical Science, Tokyo Medical and Dental University, Tokyo, Japan; Department of Plastic and Reconstructive Surgery, Juntendo University Graduate School of Medicine, Tokyo, Japan; Division of Genomic Technologies, RIKEN Center for Life Science Technologies, Yokohama, Japan, RIKEN Center for Developmental Biology, Kobe, Japan, RIKEN Advanced Center for Computing and Communication, Preventive Medicine and Applied Genomics Unit, Yokohama, Japan; Division of Genomic Technologies, RIKEN Center for Life Science Technologies, Yokohama, Japan, RIKEN Omics Science Center (OSC), Yokohama, Japan; RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa, Japan; Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, Barcelona, Spain; Division of Genomic Technologies, RIKEN Center for Life Science Technologies, Yokohama, Japan, RIKEN Omics Science Center (OSC), Yokohama, Japan; MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, United Kingdom; Biotechnology Research Institute for Drug Discovery, National Institute of Advanced Industrial Science and Technology (AIST), Tokyo, Japan, Department of Computational Biology and Medical Sciences, University of Tokyo, Tokyo, Japan; Department of Obstetrics and Gynecology, Juntendo University, Tokyo, Japan; Harry Perkins Institute of Medical Research, and the Centre for Medical Research, University of Western Australia, QEII Medical Centre, Perth, WA, Australia; Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, United Kingdom; Division of Genomic Technologies, RIKEN Center for Life Science Technologies, Yokohama, Japan; Artificial Intelligence Research Center (AIRC), National Institute of Advanced Industrial Science and Technology (AIST), Tokyo, Japan, Biotechnology Research Institute for Drug Discovery, National Institute of Advanced Industrial Science and Technology (AIST), Tokyo, Japan, Department of Computational Biology and Medical Sciences, University of Tokyo, Tokyo, Japan; Berlin Institute for Medical Systems Biology, Max-Delbruck Centre for Molecular Medicine, Berlin, Germany; Department of Clinical Molecular Genetics, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Tokyo, Japan; The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Easter Bush, United Kingdom; Department of Ophthalmology, Osaka University Graduate School of Medicine, Suita, Japan; Science for Life Laboratory, KTH-Royal Institute of Technology, Stockholm, Sweden; Department of Informatics, University of Bergen, Bergen, Norway; Hubrecht Institute, Utrecht, Netherlands; Biozentrum, University of Basel, Basel, Switzerland, Swiss Institute of Bioinformatics, Basel, Switzerland; Department of Psychiatry and Behavioral Sciences, University of Miami Miller School of Medicine, Miami, FL, United States; Laboratorio Nazionale Consorzio Italiano Biotecnologie (LNCIB), Trieste, Italy; The Bioinformatics Centre, Department of Biology, University of Copenhagen, Copenhagen, Denmark, Biotech Research and Innovation Centre, University of Copenhagen, Copenhagen, Denmark, RIKEN Omics Science Center (OSC), Yokohama, Japan; The Bioinformatics Centre, Department of Biology, University of Copenhagen, Copenhagen, Denmark, Biotech Research and Innovation Centre, University of Copenhagen, Copenhagen, Denmark; Science for Life Laboratory, KTH-Royal Institute of Technology, Stockholm, Sweden; Division of Biological and Environmental Sciences & Engineering, King Abdullah University of Science and Technology (KAUST), Thuwal, Saudi Arabia; Vavilov Institute of General Genetics, Russian Academy of Sciences, Moscow, Russian Federation; Department of Psychiatry and Behavioral Sciences, University of Miami Miller School of Medicine, Miami, FL, United States; Centre for Molecular Medicine and Therapeutics at the Child and Family Research Institute, Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada, Department of Medical Genetics, Centre for Molecular Medicine and Therapeutics, Child and Family Research Institute, University of British Columbia, Vancouver, BC, Canada; Division of Genomic Technologies, RIKEN Center for Life Science Technologies, Yokohama, Japan; Division of Genomic Technologies, RIKEN Center for Life Science Technologies, Yokohama, Japan, RIKEN Omics Science Center (OSC), Yokohama, Japan; The University of Melbourne Centre for Stem Cell Systems, School of Biomedical Sciences, The University of Melbourne, Victoria, Australia, Walter and Eliza Hall Institute of Medical Research, Melbourne, VIC, Australia; Harry Perkins Institute of Medical Research, and the Centre for Medical Research, University of Western Australia, QEII Medical Centre, Perth, WA, Australia; Australian Institute for Bioengineering and Nanotechnology (AIBN), University of Queensland, Brisbane St Lucia, QLD, Australia; Division of Genomic Technologies, RIKEN Center for Life Science Technologies, Yokohama, Japan, RIKEN Omics Science Center (OSC), Yokohama, Japan; Division of Genomic Technologies, RIKEN Center for Life Science Technologies, Yokohama, Japan; Department of Biological Information, Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, Tokyo, Japan; Department of Biochemistry, Nihon University School of Dentistry, Tokyo, Japan; Graduate School of Medicine, Tohoku University, Sendai, Japan; Database Center for Life Science, Research Organization of Information and Systems, Tokyo, Japan; Division of Genomic Technologies, RIKEN Center for Life Science Technologies, Yokohama, Japan, RIKEN Omics Science Center (OSC), Yokohama, Japan; RIKEN Preventive Medicine and Diagnosis Innovation Program, Wako, Saitama, Japan; Faculty of Information Science and Technology, Osaka Institute of Technology, Hirakata, Japan; Division of Genomic Technologies, RIKEN Center for Life Science Technologies, Yokohama, Japan; Research Center for Genomic Medicine, Saitama Medical University, Saitama, Japan; RIKEN BioResource Center, Tsukuba, Japan; Department of Ophthalmology and Visual Science, Tohoku University Graduate School of Medicine, Sendai, Japan; Laboratory Animal Research Center, Institute of Medical Science, University of Tokyo, Tokyo, Japan; Division of Genomic Technologies, RIKEN Center for Life Science Technologies, Yokohama, Japan; RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa, Japan; Division of Genomic Technologies, RIKEN Center for Life Science Technologies, Yokohama, Japan, Department of Ophthalmology, Osaka University Graduate School of Medicine, Suita, Japan; The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Easter Bush, United Kingdom; MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, United Kingdom; Department of Biosciences and Nutrition, Karolinska Institute, Stockholm, Sweden; RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa, Japan; The SKI Stem Cell Research Facility, The Center for Stem Cell Biology and Developmental Biology Program, Sloan Kettering Institute, New York, NY, United States; Department of Medical Genetics, Centre for Molecular Medicine and Therapeutics, Child and Family Research Institute, University of British Columbia, Vancouver, BC, Canada; Area of Neuroscience, International School for Advanced Studies (SISSA), Trieste, Italy, Department of Health Sciences, Universit del Piemonte Orientale, Novara, Italy; Science for Life Laboratory, KTH-Royal Institute of Technology, Stockholm, Sweden; SANOFI R&D, Translational Sciences, Chilly Mazarin, France; RIKEN Center for Integrative Medical Sciences, Yokohama, Kanagawa, Japan; Institut de Biologie Computationnelle, Montpellier, France, LIRMM, Univ Montpellier, CNRS, Montpellier, France | 57219827232; 57219826071; 57200335303; 57200333693; 14034705100; 7003562245; 35355246400; 57218355452; 24176191000; 24176384200; 56118066500; 35277508200; 57194017574; 6603860842; 27168688500; 57207902589; 56117212300; 57224314216; 6506529160; 8901741400; 15831377100; 59828734900; 56188785000; 57218681123; 56532035600; 53871090400; 57194222463; 13005726000; 7202299821; 7201372152; 57224306913; 56701054100; 7005147127; 7006368112; 35418283400; 7202856244; 55542361800; 55519225900; 7003823175; 57221467333; 35377862500; 57224313808; 57189335049; 6603147008; 6603371059; 15842904600; 6504747900; 57473846300; 7801310469; 15070243200; 26638009800; 7003952389; 57224317328; 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55628548236; 56531290600; 7007113088; 6508253473; 57208914439; 14833332700; 57190047358; 7401962034; 23096238000; 6603082428; 6603052044; 57210179569; 57214748425; 59776186300; 6603719506; 14016587200; 55653509000; 7004637483; 57216140985; 57224312871; 10138861500; 55311563900; 6506655769; 16054030900; 56166304900; 7003939259; 7005583789; 55926176300; 58957708100; 55545639700; 59879886500; 55277840500; 7201859950; 57204280274; 55260574400; 55565724500; 59102444400; 57070836300; 57070733900; 7102054125; 57221344339; 55567208800; 7402347486; 55736257900; 35068748500; 6603725380; 55883113200; 8976797900; 7406241921; 55433907400; 8288532400; 56611415300; 57219784866; 15842373300; 7004731770; 57224317676; 7202067824; 57146920300; 7003633663; 7102229224; 23391061200; 7003315037; 9271267600; 55770086700; 6507291437; 36103172600; 56126254200; 55773256100; 25224158700; 55619103500; 7006085495; 57221097180; 14631264400; 56095506200; 7202578262; 6508000646; 6603051622; 55511929900; 59890405400; 55585001500; 55244292500; 57225031104; 59715883000; 57221711572; 8584994100; 39763442500; 6506019622; 56685479400; 55912866000; 8662620600; 59891277900; 57196279425; 59580768000; 55817243100; 7405926185; 55318233600; 57190979818; 8746889700; 23670682400; 35235792800; 55684360700; 23471570400; 57202550836; 57871579700; 7801511930 | brehelin@lirmm.fr;charles.lecellier@igmm.cnrs.fr; | Nature Communications | NAT COMMUN | N/A | 2041-1723 | 12 | 1 | SCIE | MULTIDISCIPLINARY SCIENCES | 2021 | 17.694 | 7.4 | 0.79 | 2025-07-30 | 16 | A549 Cells; Animals; Base Sequence; Computational Biology; Deep Learning; Enhancer Elements, Genetic; Genome, Human; High-Throughput Nucleotide Sequencing; Humans; Mice; Microsatellite Repeats; Neural Networks, Computer; Neurodegenerative Diseases; Polymorphism, Genetic; Promoter Regions, Genetic; Transcription Initiation Site; Transcription Initiation, Genetic; 7 methylguanosine; DNA; microRNA; microsatellite DNA; artificial neural network; DNA; gene expression; genetic analysis; genetic marker; genetic variation; probe; trapping; A-549 cell line; Article; cellular distribution; controlled study; convolutional neural network; cytoplasm; deep learning; deep neural network; diseases; DNA polymorphism; expression quantitative trait locus; genetic variability; human; human cell; short tandem repeat; transcription initiation; transcription initiation site; animal; biology; degenerative disease; enhancer region; genetic polymorphism; genetics; high throughput sequencing; human genome; metabolism; mouse; nucleotide sequence; procedures; promoter region | English | Final | 2021 | 10.1038/s41467-021-23143-7 | 바로가기 | 바로가기 | 바로가기 | ||||||||
| ○ | Meeting Abstract | Lifetime cancer risks from occupational radiation exposure among workers at interventional radiology departments | Lee, Won Jin; Bang, Ye Jin; Kim, Young Min; Cho, Sung Bum | Korea Univ, Coll Med, Seoul, South Korea; Kyungpook Natl Univ, Daegu, South Korea | INTERNATIONAL JOURNAL OF EPIDEMIOLOGY | INT J EPIDEMIOL | 0300-5771 | 1464-3685 | 50 | SCIE | PUBLIC, ENVIRONMENTAL & OCCUPATIONAL HEALTH | 2021 | 9.685 | 7.4 | 0 | English | 2021 | 2021-09 | 바로가기 | 바로가기 | |||||||||||||||||
| ○ | ○ | Article | Mastocytosis-derived extracellular vesicles deliver miR-23a and miR-30a into pre-osteoblasts and prevent osteoblastogenesis and bone formation | Osteoporosis and other manifestations of bone disease are frequent in patients with systemic mastocytosis (SM) in association with the presence of mast cell infiltrates in bone marrow, although the mechanisms behind bone disease remain poorly understood. We find that extracellular vesicles (EVs) released by neoplastic mast cells and present in the serum of patients with SM (SM-EVs) block osteoblast differentiation and mineralization in culture, and when injected into mice diminish the expression of osteoblast markers, and trabecular bone volume and microarchitecture. We demonstrate that miRNA-30a and miRNA-23a, increased in SM-EVs and neoplastic mast cell-derived EVs, attenuate osteoblast maturation by suppressing expression of RUNX2 and SMAD1/5, essential drivers of osteogenesis. Thus, SM-EVs carry and deliver miRNAs that epigenetically interfere with bone formation and can contribute to bone mass reduction in SM. These findings also suggest possibilities for novel approaches to the management of bone disease in mast cell proliferative disorders. Osteoporosis and bone disease are common in patients with systemic mastocytosis. Here, the authors show that extracellular vesicles released by neoplastic mast cells of the patients block osteoblast differentiation and bone mineralization when injected into mice, via a mechanism involving suppression of osteogenic factors via miRNA-30a and miRNA-23a. | Kim, Do-Kyun; Bandara, Geethani; Cho, Young-Eun; Komarow, Hirsh D.; Donahue, Danielle R.; Karim, Baktiar; Baek, Moon-Chang; Kim, Ho Min; Metcalfe, Dean D.; Olivera, Ana | NIAID, Mast Cell Biol Sect, Lab Allerg Dis, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA; Inst Basic Sci IBS, Ctr Biomol & Cellular Struct, Daejeon, South Korea; NIAAA, Sect Mol Pharmacol & Toxicol, Lab Membrane Biochem & Biophys, NIH, Bethesda, MD USA; Andong Natl Univ, Dept Food & Nutr, Andong, Kyungpook, South Korea; NINDS, Mouse Imaging Facil, NIH, Bethesda, MD USA; Leidos Biomed Res Inc, NCI, Mol Histopathol Lab, Frederick Natl Lab Canc Res,NIH, Frederick, MD 21701 USA; Kyungpook Natl Univ, Sch Med, Exosome Convergence Res Ctr ECRC, Dept Mol Med,CMRI, Daegu, South Korea; Jeonbuk Natl Univ, Korea Zoonosis Res Inst, Iksan, Jeonbuk, South Korea | ; Kim, Ho/G-2712-2011; kim, david/AAA-4537-2020 | 55568033800; 6601976605; 56390104900; 27168135200; 36552142100; 6602918914; 7006013097; 58122841900; 35414586100; 7007058348 | ana.olivera@nih.gov; | NATURE COMMUNICATIONS | NAT COMMUN | 2041-1723 | 12 | 1 | SCIE | MULTIDISCIPLINARY SCIENCES | 2021 | 17.694 | 7.4 | 2.47 | 2025-07-30 | 54 | 54 | MAST-CELL LINE; EXOSOMAL MIRNAS; OSTEOPOROSIS; OSTEOCLASTOGENESIS; DIFFERENTIATION; PATHOGENESIS; REGULATORS; DISEASES | Adolescent; Adult; Aged; Aged, 80 and over; Animals; Calcification, Physiologic; Cell Differentiation; Cell Line; Child; Child, Preschool; Core Binding Factor Alpha 1 Subunit; Extracellular Vesicles; Female; Humans; Male; Mast Cells; Mastocytosis; Mice; Mice, Inbred C57BL; MicroRNAs; Middle Aged; Myeloproliferative Disorders; Osteoblasts; Osteogenesis; Smad1 Protein; Smad5 Protein; Young Adult; alkaline phosphatase; CD9 antigen; cell protein; collagen type 1; G protein coupled receptor; immunoglobulin E receptor; microRNA; microRNA 23a; microRNA 30a; mitogen activated protein kinase 1; nanoparticle; osteopontin; Smad1 protein; Smad5 protein; transcription factor RUNX2; unclassified drug; microRNA; MIRN23a microRNA, human; Mirn23b microRNA, mouse; MIRN30 microRNA, human; MIRN30a microRNA, mouse; RUNX2 protein, human; Smad1 protein; Smad5 protein; transcription factor RUNX2; biomarker; bone; cell; cell component; differentiation; disease; gene expression; maturation; protein; RNA; serum; adult; animal experiment; animal model; Article; bone development; bone mass; bone metabolism; bone mineralization; cell differentiation; cell proliferation; clinical article; controlled study; electron microscopy; exosome; extracellular calcium; fragility fracture; HMC-1.1 cell line; HMC-1.2 cell line; human; human cell; immunohistochemistry; male; mast cell; mastocytosis; mouse; nonhuman; ossification; osteoblast; osteoclast; osteoclastogenesis; osteopenia; osteoporosis; protein expression; regulatory mechanism; scanning electron microscopy; trabecular bone; adolescent; aged; animal; bone development; C57BL mouse; cell line; child; exosome; female; mastocytosis; metabolism; middle aged; myeloproliferative disorder; osteoblast; physiology; preschool child; very elderly; young adult | English | 2021 | 2021-05-05 | 10.1038/s41467-021-22754-4 | 바로가기 | 바로가기 | 바로가기 | 바로가기 | ||||
| ○ | ○ | Article | Relief of excited-state antiaromaticity enables the smallest red emitter | Commonly, large pi-conjugated systems facilitate low-energy electronic transitions. Here, the authors demonstrate that the relief of excited-state antiaromaticity of the benzene core leads to large Stokes shifts, and allows the construction of emitters covering the entire visible spectrum without the need of extending pi-conjugation. It is commonly accepted that a large pi-conjugated system is necessary to realize low-energy electronic transitions. Contrary to this prevailing notion, we present a new class of light-emitters utilizing a simple benzene core. Among different isomeric forms of diacetylphenylenediamine (DAPA), o- and p-DAPA are fluorescent, whereas m-DAPA is not. Remarkably, p-DAPA is the lightest (FW = 192) molecule displaying red emission. A systematic modification of the DAPA system allows the construction of a library of emitters covering the entire visible color spectrum. Theoretical analysis shows that their large Stokes shifts originate from the relief of excited-state antiaromaticity, rather than the typically assumed intramolecular charge transfer or proton transfer. A delicate interplay of the excited-state antiaromaticity and hydrogen bonding defines the photophysics of this new class of single benzene fluorophores. The formulated molecular design rules suggest that an extended pi-conjugation is no longer a prerequisite for a long-wavelength light emission. | Kim, Heechan; Park, Woojin; Kim, Younghun; Filatov, Michael; Choi, Cheol Ho; Lee, Dongwhan | Seoul Natl Univ, Dept Chem, Seoul, South Korea; Kyungpook Natl Univ, Dept Chem, Daegu, South Korea | Choi, Cheol Ho/AAA-4705-2020 | 57213118053; 57223952329; 55548794400; 7005134246; 7402958948; 55619306281 | mike.filatov@gmail.com;cchoi@khu.ac.kr;dongwhan@snu.ac.kr;cchoi@knu.ac.kr; | NATURE COMMUNICATIONS | NAT COMMUN | 2041-1723 | 12 | 1 | SCIE | MULTIDISCIPLINARY SCIENCES | 2021 | 17.694 | 7.4 | 3.37 | 2025-07-30 | 62 | 85 | LARGE STOKES SHIFT; ORGANIC-PHOTOCHEMISTRY; AROMATICITY; FLUOROPHORES; FLUORESCENCE; STRATEGIES; BENZENE; DESIGN; COMPLEXES; RESONANCE | aromatic compound; benzene; diacetylphenylenediamine; phenylenediamine derivative; unclassified drug; benzene; chemical bonding; color; fluorescence; light effect; theoretical study; visible spectrum; Article; chemical modification; color; conjugation; controlled study; hydrogen bond; infrared radiation; isomer; molecular weight; proton transport; theoretical model | English | 2021 | 2021-09-13 | 10.1038/s41467-021-25677-2 | 바로가기 | 바로가기 | 바로가기 | 바로가기 | ||||
| ○ | ○ | Article | Transcranial alternating current stimulation entrains alpha oscillations by preferential phase synchronization of fast-spiking cortical neurons to stimulation waveform | Computational modeling and human studies suggest that transcranial alternating current stimulation (tACS) modulates alpha oscillations by entrainment. Yet, a direct examination of how tACS interacts with neuronal spiking activity that gives rise to the alpha oscillation in the thalamo-cortical system has been lacking. Here, we demonstrate how tACS entrains endogenous alpha oscillations in head-fixed awake ferrets. We first show that endogenous alpha oscillations in the posterior parietal cortex drive the primary visual cortex and the higher-order visual thalamus. Spike-field coherence is largest for the alpha frequency band, and presumed fast-spiking inhibitory interneurons exhibit strongest coupling to this oscillation. We then apply alpha-tACS that results in a field strength comparable to what is commonly used in humans (<0.5mV/mm). Both in these ferret experiments and in a computational model of the thalamo-cortical system, tACS entrains alpha oscillations by following the theoretically predicted Arnold tongue. Intriguingly, the fast-spiking inhibitory interneurons exhibit a stronger entrainment response to tACS in both the ferret experiments and the computational model, likely due to their stronger endogenous coupling to the alpha oscillation. Our findings demonstrate the in vivo mechanism of action for the modulation of the alpha oscillation by tACS. Transcranial alternating current stimulation (tACS) can modulate cortical oscillations and associated long-lasting cognitive and behavioral functions in humans. Here, the authors provide in vivo evidence in ferrets on the mechanism of how weak electric fields in tACS can entrain neuronal activity. | Huang, Wei A.; Stitt, Iain M.; Negahbani, Ehsan; Passey, D. J.; Ahn, Sangtae; Davey, Marshall; Dannhauer, Moritz; Doan, Thien T.; Hoover, Anna C.; Peterchev, Angel V.; Radtke-Schuller, Susanne; Froehlich, Flavio | Univ N Carolina, Dept Psychiat, Chapel Hill, NC 27515 USA; Univ N Carolina, Carolina Ctr Neurostimulat, Chapel Hill, NC 27515 USA; Univ N Carolina, Neurosci Ctr, Chapel Hill, NC 27515 USA; Univ N Carolina, Dept Math, Chapel Hill, NC 27515 USA; Kyungpook Natl Univ, Sch Elect & Elect Engn, Daegu, South Korea; Duke Univ, Dept Psychiat & Behav Sci, Durham, NC USA; Duke Univ, Dept Biomed Engn, Durham, NC 27706 USA; Duke Univ, Dept Elect & Comp Engn, Durham, NC USA; Duke Univ, Dept Neurosurg, Durham, NC USA; Univ N Carolina, Dept Cell Biol & Physiol, Chapel Hill, NC 27515 USA; Univ N Carolina, Dept Biomed Engn, Chapel Hill, NC 27515 USA; Univ N Carolina, Dept Neurol, Chapel Hill, NC 27515 USA | ; Frohlich, Flavio/P-6429-2017; Ahn, Sangtae/AFQ-7342-2022; Peterchev, Angel/I-1477-2019 | 57211922947; 55368216200; 57204954867; 57217245563; 55468016100; 57219786726; 36977950300; 57219794434; 57219792262; 6603437086; 6603082480; 57204276548 | Flavio_frohlich@med.unc.edu; | NATURE COMMUNICATIONS | NAT COMMUN | 2041-1723 | 12 | 1 | SCIE | MULTIDISCIPLINARY SCIENCES | 2021 | 17.694 | 7.4 | 4.15 | 2025-07-30 | 96 | 94 | ELECTRIC-FIELDS; LINEAR-DEPENDENCE; BRAIN-STIMULATION; TACS; EXCITABILITY; POPULATIONS; MECHANISMS; FEEDBACK; SLEEP; TDCS | Alpha Rhythm; Animals; Computer Simulation; Electrodes, Implanted; Electroencephalography; Female; Ferrets; Interneurons; Magnetic Resonance Imaging; Male; Microelectrodes; Models, Animal; Models, Neurological; Nerve Net; Optogenetics; Thalamus; Tomography, X-Ray Computed; Transcranial Direct Current Stimulation; Visual Cortex; Mustela; biostimulation; detection method; experimental study; inhibition; inhibitor; modeling; article; brain cell; computer model; controlled study; human; human cell; in vivo study; interneuron; Mustela putorius furo; nonhuman; oscillation; posterior parietal cortex; spike; striate cortex; thalamocortical tract; thalamus; tongue; transcranial alternating current stimulation; wakefulness; waveform; alpha rhythm; animal; animal model; biological model; computer simulation; cytology; devices; diagnostic imaging; electrode implant; electroencephalography; female; male; microelectrode; nerve cell network; nuclear magnetic resonance imaging; optogenetics; physiology; procedures; transcranial direct current stimulation; visual cortex; x-ray computed tomography | English | 2021 | 2021-05-25 | 10.1038/s41467-021-23021-2 | 바로가기 | 바로가기 | 바로가기 | 바로가기 | ||||
| ○ | ○ | Article | Biological treatment of reverse osmosis concentrate by microalgae cultivation and utilization of the resulting algal biomass | The reverse osmosis system is one of the most advanced membrane-based water treatment technologies that can convert a variety of wastewater into drinking and industrial water. However, it has major drawbacks, including the production of a large amount of reject stream that contains concentrated nutrients. Microalgae are wellknown for their rapid growth and ability to consume excessive nutrients very efficiently under a variety of wastewater conditions. In this study, a locally isolated microalga, Chlorella sorokiniana KNUA071, was cultivated in reverse osmosis concentrate (ROC) obtained from a municipal wastewater reclamation facility that contained high levels of nutrients, ion, and metal elements. The aim was to investigate the potential of this microalga to be used in ROC treatments and the related applications of its biomass. Results showed that the C. sorokiniana KNUA071 could successfully remove 91.9% of total nitrogen (TN), 97% of total phosphorus, 98% of Mn, 100% of Al, 64% of Zn, 62% of Co, and 50% of Ni within 8 days, yielding a biomass productivity of 0.9 g dry weight L-1. This study also compared the results obtained from the Desmodesmus sp. KNUA024, which was used in the treatment of primary settled wastewater (PS) in our previously research, and was found to remove only 53.5% of TN in 8 days. C. sorokiniana KNUA071 biomass cultivated in the ROC had similar to 13.3% of lipid content while its biomass grown in the PS had similar to 28.2% of lipid content. The lipid contents of Desmodesmus sp. KNUA024 grown in the ROC and PS were similar to 29.3% and similar to 27.1%, respectively. Our findings suggest that microalgal cultivation could be employed as an effective strategy to remove nutrients and metals from ROC and at the same time produce biofuel from the lipids accumulated in the algal biomass. | Do, Jeong-Mi; Jo, Seung-Woo; Yeo, Hee-Tae; Shin, Dong Hoon; Oh, Hannah; Hong, Ji Won; Yoon, Ho-Sung | Kyungpook Natl Univ, Coll Nat Sci, Dept Biol, Daegu 41566, South Korea; Kyungpook Natl Univ, Sch Life Sci, KNU Creat BioRes Grp BK21 4, Daegu 41566, South Korea; Korea Inst Water Technol Certificat KIWATEC, Technol Dev Div, R&D & Technol Dev Team, Daegu 43008, South Korea; Korea Dyeing & Finishing Technol Inst DYETEC, Water Environm Res Dept, Daegu 41706, South Korea; Kyungpook Natl Univ, Dept Hydrogen & Renewable Energy, Daegu 41566, South Korea; Kyungpook Natl Univ, Adv Bioresource Res Ctr, Daegu 41566, South Korea | 57208562245; 56018962600; 57224478334; 57224481247; 57224469858; 57201579963; 7402990205 | jwhong@knu.ac.kr;hsy@knu.ac.kr; | JOURNAL OF WATER PROCESS ENGINEERING | J WATER PROCESS ENG | 2214-7144 | 42 | SCIE | ENGINEERING, CHEMICAL;ENGINEERING, ENVIRONMENTAL;WATER RESOURCES | 2021 | 7.34 | 7.5 | 1.13 | 2025-07-30 | 19 | 20 | Reverse osmosis concentrate; Wastewater treatment; Microalgae; Biodiesel; Soil amendment | ELECTROCHEMICAL OXIDATION; LIPID PRODUCTION; ORGANIC-MATTER; RO CONCENTRATE; WATER; REMOVAL; NITROGEN; PERFORMANCE; ADSORPTION; CHLORELLA | Biodiesel; Microalgae; Reverse osmosis concentrate; Soil amendment; Wastewater treatment | English | 2021 | 2021-08 | 10.1016/j.jwpe.2021.102157 | 바로가기 | 바로가기 | 바로가기 | 바로가기 | |||||
| ○ | ○ | Article | In-situ fabrication of ternary (3D/2D/2D) prism-like structures with dramatically enhancement on degradation of profenofos: A systemic study | In the present work, a novel (3D/2D/2D) prism-like ZGO-MOF hybrid nanocomposite was successfully prepared via two-pot hydro-thermal process and employed as a catalyst for the degradation of organic persistent pesticide such as profenofos (PF). Due to more toxicity, the removal of such organic compounds are necessary in environmental aspects. The prepared nanocomposites were characterized and well explained using FT-IR, XRD, UV-DRS, SEM-EDX, TEM, TGA-DTA, PL and BET surface area measurements. The (OH)-O-center dot and O-center dot(2)- radicals was benign effective oxidative species involved in the ZGO-MOF system for the mineralization of organic pollutants. Besides, ZGO-MOF showed excellent photo-stability over five repetitive runs for the removal of organic pesticides with minimal drop on catalytic activity. Eventually, the intended photocatalytic mechanisms and degradation pathways of PF are readily determined in detail based on experimental results. The catalyst achieves excellent efficiency of about 94 %. Possible PQ oxidative pathways and their reaction intermediates were observed by LC-MS. Therefore, the pollutant which primarily oxidize into ring-ruptured components into innocuous products like H2O, CO2 and a few in-organic salts. With the concern of its environmental friendly, low-cost, and benign simple synthesis, ZGO-MOF was expected to be a promising choice for applications in wastewater management. | Vigneshwaran, Sivakumar; Preethi, Jayaram; Park, Chang Min; Meenakshi, Sankaran | Gandhigram Rural Inst Deemed Be Univ, Dept Chem, Dindigul 624302, Tamil Nadu, India; Kyungpook Natl Univ, Dept Environm Engn, 80 Daehak Ro, Daegu 41566, South Korea | Vigneshwaran, Sivakumar/AAE-6278-2022; Meenakshi, Sankaran/AAF-5748-2020; Park, Chang Min/CAA-8506-2022; Vigneshwaran, Siva kumar/IST-9536-2023 | 57207105576; 58909614400; 57209588953; 58099005900 | vigneshwarangri@gmail.com;jpreethigri@gmail.com;cmpark@knu.ac.kr;sankaranmeenakshi2014@gmail.com; | JOURNAL OF WATER PROCESS ENGINEERING | J WATER PROCESS ENG | 2214-7144 | 39 | SCIE | ENGINEERING, CHEMICAL;ENGINEERING, ENVIRONMENTAL;WATER RESOURCES | 2021 | 7.34 | 7.5 | 0.69 | 2025-07-30 | 13 | 12 | Profenofos; ZGO-MOF; Batch experiments; Oxidative pathway; Mechanism | METAL-ORGANIC FRAMEWORK; HETEROGENEOUS PHOTOCATALYTIC DEGRADATION; IMPREGNATED CHITOSAN BEADS; GRAPHENE OXIDE; ZINC-OXIDE; EFFICIENT REMOVAL; ADSORPTION; WATER; PHOTODEGRADATION; NANOCOMPOSITES | Batch experiments; Mechanism; Oxidative pathway; Profenofos; ZGO-MOF | English | 2021 | 2021-02 | 10.1016/j.jwpe.2020.101720 | 바로가기 | 바로가기 | 바로가기 | 바로가기 | ||||
| ○ | ○ | Article | Phytoremediation of dairy wastewater using Azolla pinnata: Application of image processing technique for leaflet growth simulation | The present study assessed the phytoremediation efficiency of water fern (Azolla pinnata R.Br.) in the treatment of dairy wastewater (DWW). Batch mode experimentation was done using different dilutions (0 to 100%) of DWW transplanted with five healthy leaflets of A. pinnata. Besides this, the A. pinnata growth was captured using camera vision-based image recognition and further modeled using logistic and modified Gompertz models. The findings showed that after 14 days of phytoremediation experiments, the maximum significant (p 0.05) reduction efficiency of selected pollutant parameters of DWW i.e. pH (9.41%), electrical conductivity (61.42%), total dissolved solids (71.56%), total Kjeldahl's nitrogen (73.25%), and total phosphorus (65.37%) observed using 75% DWW dilution. Moreover, the periodically taken surface images were useful to recognize the position and number of leaflets which further helped to simulate A. pinnata growth patterns. The maximum number of leaflets (n = 20), fresh biomass (16.18 +/- 0.42 g), dry biomass (1.47 +/- 0.04 g), and chlorophyll content (3.14 +/- 0.03 mg/g fwt.) was also observed using 75% DWW treatment, respectively. The logistic model was found more robust as compared to modified Gompertz to predict leaflet production (y) as revealed from model validation results i.e. coefficient of determination (R2 0.9533) and minimum difference between experimental and modelpredicted results. Thus, the combined application of phytoremediation and image processing techniques can be used to monitor and maximize plant growth performance. | Goala, Madhumita; Yadav, Krishna Kumar; Alam, Javed; Adelodun, Bashir; Choi, Kyung Sook; Cabral-Pinto, Marina M. S.; Hamid, Ali Awadh; Alhoshan, Mansour; Ali, Fekri Abdulraqeb Ahmed; Shukla, Arun Kumar | Affiliated Assam Univ, Nehru Coll, Cachar 788098, Assam, India; Madhyanchal Profess Univ, Fac Sci & Technol, Bhopal 462044, Madhya Pradesh, India; King Saud Univ, King Abdullah Inst Nanotechnol, POB 2455, Riyadh 11451, Saudi Arabia; Kyungpook Natl Univ, Dept Agr Civil Engn, Daegu 41566, South Korea; Univ Ilorin, Dept Agr & Biosyst Engn, PMB 1515, Ilorin 240103, Nigeria; Univ Aveiro, Dept Geosci, Geobiotec Res Ctr, P-3810193 Aveiro, Portugal; King Saud Univ, Coll Engn, Chem Engn Dept, POB 2455, Riyadh 11451, Saudi Arabia | ; Adelodun, Bashir/O-2941-2018; Pinto, Marina/AAA-6633-2022; Yadav, Dr. Krishna Kumar/ABE-6962-2021; Shukla, Arun Kumar/F-3515-2018; Alhoshan, Mansour/ABD-2914-2020; Alam, Javed/E-9639-2013; Ali, Fekri/KLC-6315-2024 | 57221943148; 57202908705; 59246466100; 57193774482; 54392662900; 22133337700; 57221730114; 6505500841; 57194499372; 58161614900 | envirokrishna@gmail.com;javaalam@ksu.edu.sa; | JOURNAL OF WATER PROCESS ENGINEERING | J WATER PROCESS ENG | 2214-7144 | 42 | SCIE | ENGINEERING, CHEMICAL;ENGINEERING, ENVIRONMENTAL;WATER RESOURCES | 2021 | 7.34 | 7.5 | 2.65 | 2025-07-30 | 38 | 46 | Azolla pinnata; Dairy wastewater; Image recognition; Phytoremediation; Pollution | SYSTEM; SCALE | Azolla pinnata; Dairy wastewater; Image recognition; Phytoremediation; Pollution | English | 2021 | 2021-08 | 10.1016/j.jwpe.2021.102152 | 바로가기 | 바로가기 | 바로가기 | 바로가기 | ||||
| ○ | Article | Use of packed scrap iron anodes for continuous electrochemical Cr(VI) reduction process in electroplating wastewater treatment | The performance of an electrochemical reduction process was investigated for the treatment Cr(VI)-containing electroplating wastewater using a continuous-flow scrap iron packed column as an sacrificial anode. The effects of the key operating parameters including hydraulic retention time (HRT), current supply ratio (CSR), and inlet Cr(VI) concentration were systematically studied. With a fixed CSR of 106%, the HRT has no impact on Cr (VI) removal, but energy consumption increased with decreasing HRT. A complete Cr(VI) removal was obtained with a final ORP of approximately -100 mV. Increasing the inlet Cr(VI) concentration caused an inefficient removal efficiency of Cr(VI) with an increases in ORP. In contrast, Cr(VI) removal remained virtually unchanged, but ORP was dramatically decreased, when the influent Cr(VI) concentration decreased. Continuous and complete Cr(VI) reduction via electrochemical reactions can be achieved by the ORP range of -200 to -100 mV. The operating cost using continuous flow treatments with HRT of 60 min required less than batch reactor treatment around 40-57%. | Ho, Chao-Chuan; Yu, Jui-Shuan; Yang, Shao-Wei; Ya, Vinh; Le, Hoang Anh; Cheng, Liao-Ping; Choo, Kwang-Ho; Li, Chi-Wang | Tamkang Univ, Dept Chem & Mat Engn, New Taipei 25137, Taiwan; Taipei Univ Marine Technol, Dept Travel Management, 150,Sec 3,BinHai Rd, New Taipei 25172, Taiwan; Tamkang Univ, Dept Water Resources & Environm Engn, 151 Yingzhuan Rd, New Taipei 25137, Taiwan; Dalat Univ, Fac Chem & Environm, Da Lat, Vietnam; Univ Sci, Fac Environm, Ho Chi Minh City, Vietnam; Vietnam Natl Univ, Ho Chi Minh City, Vietnam; Kyungpook Natl Univ, Dept Environm Engn, 80 Daehak Ro, Daegu 702701, South Korea | Li, Chi-Wang/G-1254-2015; Choo, Kwang-Ho/A-3456-2016 | chiwang@mail.tku.edu.tw; | JOURNAL OF WATER PROCESS ENGINEERING | J WATER PROCESS ENG | 2214-7144 | 42 | SCIE | ENGINEERING, CHEMICAL;ENGINEERING, ENVIRONMENTAL;WATER RESOURCES | 2021 | 7.34 | 7.5 | 20 | Continuous electrochemical reduction; Cr(VI) reduction; Electroplating wastewater; Scrap iron packed column; Oxidation-reduction potential | HEXAVALENT CHROMIUM REDUCTION; REMOVAL; PH; CR(III) | English | 2021 | 2021-08 | 10.1016/j.jwpe.2021.102191 | 바로가기 | 바로가기 | 바로가기 | |||||||||||
| ○ | ○ | Article | Hevin-calcyon interaction promotes synaptic reorganization after brain injury | Hevin, also known as SPARC-like protein 1 (SPARCL1 or SC1), is a synaptogenic protein secreted by astrocytes and modulates the formation of glutamatergic synapses in the developing brain by interacting with synaptic adhesion proteins, such as neurexin and neuroligin. Here, we identified the neuron-specific vesicular protein calcyon as a novel interaction partner of hevin and demonstrated that this interaction played a pivotal role in synaptic reorganization after an injury in the mature brain. Astrocytic hevin was upregulated post-injury in a photothrombotic stroke model. Hevin was fragmented by MMP3 induced during the acute stage of brain injury, and this process was associated with severe gliosis. At the late stage, the functional hevin level was restored as MMP3 expression decreased. The C-terminus of hevin interacted with the N-terminus of calcyon. By using RNAi and binding competitor peptides in an ischemic brain injury model, we showed that this interaction was crucial in synaptic and functional recoveries in the sensory-motor cortex, based on histological and electrophysiological analyses. Regulated expression of hevin and calcyon and interaction between them were confirmed in a mouse model of traumatic brain injury and patients with chronic traumatic encephalopathy. Our study provides direct evidence for the causal relationship between the hevin-calcyon interaction and synaptic reorganization after brain injury. This neuron-glia interaction can be exploited to modulate synaptic reorganization under various neurological conditions. | Kim, Jong-Heon; Jung, Hyun-Gug; Kim, Ajung; Shim, Hyun Soo; Hyeon, Seung Jae; Lee, Young-Sun; Han, Jin; Jung, Jong Hoon; Lee, Jaekwang; Ryu, Hoon; Park, Jae-Yong; Hwang, Eun Mi; Suk, Kyoungho | Kyungpook Natl Univ, Brain Sci & Engn Inst, Daegu, South Korea; Korea Inst Sci & Technol, Brain Sci Inst, Ctr Funct Connect, Seoul, South Korea; Korea Univ, Coll Hlth Sci, Sch Biosyst & Biomed Sci, Seoul, South Korea; Korea Inst Sci & Technol, Brain Sci Inst, Ctr Neurosci, Seoul, South Korea; Kyungpook Natl Univ, Sch Med, Dept Pharmacol, Daegu, South Korea; Kyungpook Natl Univ, Sch Med, Dept Biomed Sci, Daegu, South Korea; Korea Food Res Inst, Res Grp Funct Food Mat, Wonju, South Korea; VA Boston Healthcare Syst, Boston, MA USA; Boston Univ, Alzheimers Dis Ctr, Boston, MA USA; Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA | ; Lee, Jongmin/Q-4909-2019; Hwang, Eun Mi/HHN-3030-2022; Ryu, Hoon/MCJ-9411-2025 | 57203324811; 56179534300; 57193908454; 57563797200; 57191974819; 56092261200; 57218360938; 57194273651; 57206732862; 7202277209; 57206479071; 7101826741; 7005114595 | emhwang@kist.re.kr;ksuk@knu.ac.kr; | CELL DEATH AND DIFFERENTIATION | CELL DEATH DIFFER | 1350-9047 | 1476-5403 | 28 | 9 | SCIE | BIOCHEMISTRY & MOLECULAR BIOLOGY;CELL BIOLOGY | 2021 | 12.073 | 7.6 | 0.67 | 2025-07-30 | 14 | 14 | CENTRAL-NERVOUS-SYSTEM; ASTROCYTE-SECRETED PROTEINS; FUNCTIONAL RECOVERY; TENASCIN-C; PLASTICITY; SYNAPSES; RECEPTOR; ROLES | Animals; Brain Injuries; Calcium-Binding Proteins; Extracellular Matrix Proteins; Humans; Male; Membrane Proteins; Mice; Synapses; AMPA receptor; binding protein; calcyon; disks large homolog 4; hevin; membrane protein; NLG1B protein; osteonectin; stromelysin; unclassified drug; vesicular glutamate transporter 1; vesicular glutamate transporter 2; calcium binding protein; calcyon; membrane protein; scleroprotein; Sparcl1 protein, mouse; adult; amino terminal sequence; animal cell; animal experiment; animal model; Article; biomolecular fluorescence complementation assay; brain injury; carboxy terminal sequence; chronic traumatic encephalopathy; coimmunoprecipitation; controlled study; excitatory postsynaptic potential; gliosis; histology; human; human cell; immunoblotting; immunohistochemistry; male; mouse; nerve cell plasticity; nonhuman; photothrombotic stroke; protein expression; protein interaction assay; protein protein interaction; reverse transcription polymerase chain reaction; RNA interference; sensorimotor cortex; spontaneous excitatory postsynaptic current; synapse; synaptic reorganization; synaptogenesis; traumatic brain injury; upregulation; whole cell patch clamp; animal; brain injury; metabolism | English | 2021 | 2021-09 | 10.1038/s41418-021-00772-5 | 바로가기 | 바로가기 | 바로가기 | 바로가기 | |||
| ○ | Editorial Material | Infographic: Mid-term outcomes after the surgical treatment of atypical femoral fractures MINIMUM THREE-YEAR FOLLOW-UP | Jeong, S-Y; Hwang, K-T; Oh, C-W; Kim, J-W; Sohn, O. J.; Kim, J. W.; Cho, Y-H; Park, K. C. | Hanyang Univ, Dept Orthopaed Surg, Guri Hosp, Guri, South Korea; Hanyang Univ, Dept Orthopaed Surg, Guri Hosp, Orthopaed Surg, Guri, South Korea; Hanyang Univ, Coll Med, Orthopaed Surg, Seoul, South Korea; Hanyang Univ, Coll Med, Trauma, Seoul, South Korea; Kyungpook Natl Univ Hosp, Dept Orthoped Surg, Orthopaed Surg, Daegu, South Korea; Kyungpook Natl Univ Hosp, Dept Orthoped Surg, Daegu, South Korea; Yeungnam Univ, Orthopaed Surg, Gyongsan, South Korea; Yeungnam Univ, Gyongsan, South Korea; Univ Ulsan, Asan Med Ctr, Orthopaed Surg, Coll Med, Seoul, South Korea; Univ Ulsan, Asan Med Ctr, Dept Orthopaed Surg, Coll Med, Seoul, South Korea; Daegu Fatima Hosp, Orthopaed Surg Dept, Daegu, South Korea; Daegu Fatima Hosp, Daegu, South Korea | Hwang, Kyu/R-7249-2016 | kcpark@hanyang.ac.kr; | BONE & JOINT JOURNAL | BONE JOINT J | 2049-4394 | 103B | 11 | SCIE | ORTHOPEDICS;SURGERY | 2021 | 5.385 | 7.6 | 0 | English | 2021 | 2021-11 | 10.1302/0301-620x.103b11.bjj-2021-1428 | 바로가기 | 바로가기 | 바로가기 | |||||||||||||
| ○ | ○ | Article | Interactions of Spiritual Well-Being, Symptoms, and Quality of Life in Patients Undergoing Treatment for Non-Small Cell Lung Cancer: A Cross-Sectional Study | Objectives: To investigate the relationship of spiritual well-being and quality of life (QOL) in patients undergoing treatment for non-small cell lung cancer (NSCLC) and to identify the role of four different symptoms (ie, appetite loss, dyspnea, pain, and fatigue) in mediating this relationship Data Sources: A total of 132 consecutive patients undergoing chemotherapy, radiotherapy, or concurrent chemoradiotherapy for NSCLC from National University Hospital were examined. Symptoms were assessed using the symptom subscale of the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-C30 (QLQ-C30). Spiritual well-being was assessed using the Functional Assessment of Chronic Illness Therapy-Spiritual Well-Being scale. Global QOL was assessed using the item on global health status from the European Organization for Research and Treatment of Cancer. Data of all self-reported surveys were analyzed using serial multiple mediation analysis. Conclusion: Spiritual well-being directly affected QOL in patients undergoing treatment for NSCLC. In addition, a serial multiple mediation model showed causal relationships of spiritual well-being on appetite loss, appetite loss on dyspnea, dyspnea on pain, pain on fatigue, and fatigue on QOL. Implications for Nursing Practice:: Providing integrated care that considers spiritual well-being may improve the QOL of patients undergoing treatment for NSCLC. Our findings emphasized the need to conduct routine assessments of spiritual well-being and symptoms when characterizing patient QOL. (c) 2021 Elsevier Inc. All rights reserved. | Lee, Myung Kyung | Kyungpook Natl Univ, Coll Nursing, Res Inst Nursing Sci, 680 Gukchaebosangro, Daegu 41944, South Korea | 40661513200 | mlee@knu.ac.kr; | SEMINARS IN ONCOLOGY NURSING | SEMIN ONCOL NURS | 0749-2081 | 1878-3449 | 37 | 2 | SCIE;SSCI | NURSING;ONCOLOGY | 2021 | 3.527 | 7.6 | 1.65 | 2025-07-30 | 16 | 19 | Quality of life; Symptoms; Spiritual well-being; Lung cancer | EUROPEAN-ORGANIZATION; PAIN; FATIGUE; CARE; PEOPLE; NEEDS; CHEMOTHERAPY; MANAGEMENT; DISTRESS; CLUSTER | Lung cancer; Quality of life; Spiritual well-being; Symptoms | English | 2021 | 2021-04 | 10.1016/j.soncn.2021.151139 | 바로가기 | 바로가기 | 바로가기 | 바로가기 | |||
| ○ | Article | Mid-term outcomes after the surgical treatment of atypical femoral fractures Minimum Three-Year Follow-Up | Aims: The incidence of atypical femoral fractures (AFFs) continues to increase. However, there are currently few long-term studies on the complications of AFFs and factors affecting them. Therefore, we attempted to investigate the outcomes, complications, and risk factors for complication through mid-term follow-up of more than three years. Methods: From January 2003 to January 2016, 305 patients who underwent surgery for AFFs at six hospitals were enrolled. After exclusion, a total of 147 patients were included with a mean age of 71.6 years (48 to 89) and 146 of whom were female. We retrospectively evaluated medical records, and reviewed radiographs to investigate the fracture site, femur bowing angle, presence of delayed union or nonunion, contralateral AFFs, and peri-implant fracture. A statistical analysis was performed to identify the significance of associated factors. Results: The mean follow-up period was 70.2 months (36 to 191). There were 146 AFFs (99.3%) in female patients and the mean age was 71.6 years (48 to 89). The AFFs were located in the subtrochanter and shaft in 52 cases (35.4%) and 95 (64.6%), respectively. The preoperative mean anterior/lateral femoral bowing angles were 10.5° (SD 5.7°)/6.1° (SD 6.2°). The postoperative mean anterior/lateral bowing values were changed by 8.7° (SD 5.4°)/4.6° (SD 5.9°). Bisphosphonates had been used contemporarily in 115 AFFs (78.2%) for a mean of 52.4 months (1 to 204; SD 45.5) preoperatively. Nailing was performed in 133 AFFs (90.5%), and union was obtained at a mean of 23.6 weeks (7 to 85). Delayed union occurred in 41 (27.9%), and nonunion occurred in 13 (8.8%). Contralateral AFF occurred in 79 patients (53.7%), and the use of a bisphosphonate significantly influenced the occurrence of contralateral AFFs (p = 0.019). Peri-implant fractures occurred in a total of 13 patients (8.8%), and a significant increase was observed in cases with plating (p = 0.021) and high grade of postoperative anterolateral bowing (p = 0.044). Conclusion: The use of a bisphosphonate was found to be a risk factor for contralateral AFF, and high-grade postoperative anterolateral bowing and plate fixation significantly increased the occurrence of peri-implant fractures. Long-term follow-up studies on the bilaterality of AFFs and peri-implant fractures are warranted. © 2021 The British Editorial Society of Bone & Joint Surgery. | Jeong, S-Y.; Hwang, K.-T.; Oh, C.-W.; Kim, J.-W.; Sohn, O.J.; Kim, J.W.; Cho, Y.-H.; Park, K.C. | Department of Orthopedic Surgery, Hanyang University Guri Hospital, Guri, South Korea; Hanyang University College of Medicine, Seoul, South Korea; Department of Orthopedic Surgery, Kyungpook National University Hospital, Daegu, South Korea; Department of Orthopedic Surgery, Kyungpook National University Hospital, Daegu, South Korea; Yeungnam University, Gyeongsan, South Korea; Department of Orthopaedic Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea; Daegu Fatima Hospital, Daegu, South Korea; Department of Orthopedic Surgery, Hanyang University Guri Hospital, Guri, South Korea | 57210285288; 35336689700; 22135834200; 22951329000; 14043970900; 55898554400; 56802979600; 56062454500 | kcpark@hanyang.ac.kr; | Bone and Joint Journal | BONE JOINT J | 2049-4394 | 2049-4394 | 103 B | 11 | SCIE | ORTHOPEDICS;SURGERY | 2021 | 5.385 | 7.6 | 0.46 | 2025-07-30 | 5 | Aged; Aged, 80 and over; Female; Femoral Fractures; Follow-Up Studies; Humans; Male; Middle Aged; Postoperative Complications; Retrospective Studies; Risk Factors; Time Factors; Treatment Outcome; bisphosphonic acid derivative; calcium; steroid; vitamin D; adult; aged; Article; bipolar hemiarthroplasty; bone bowing; bone density; bone radiography; clinical outcome; comparative study; controlled study; digital imaging and communications in medicine; female; femoral shaft; femur length; femur shaft fracture; femur subtrochanteric fracture; follow up; fracture nonunion; fracture treatment; human; intramedullary nailing; major clinical study; male; medical record review; middle aged; multicenter study; osteoporosis; periprosthetic fracture; postoperative complication; preoperative period; reoperation; retrospective study; surgical risk; very elderly; femur fracture; postoperative complication; risk factor; time factor; treatment outcome | English | Final | 2021 | 10.1302/0301-620x.103b11.bjj-2021-0416.r1 | 바로가기 | 바로가기 | 바로가기 | ||||||||
| ○ | ○ | Article | RUNX3 methylation drives hypoxia-induced cell proliferation and antiapoptosis in early tumorigenesis | Inactivation of tumor suppressor Runt-related transcription factor 3 (RUNX3) plays an important role during early tumorigenesis. However, posttranslational modifications (PTM)-based mechanism for the inactivation of RUNX3 under hypoxia is still not fully understood. Here, we demonstrate a mechanism that G9a, lysine-specific methyltransferase (KMT), modulates RUNX3 through PTM under hypoxia. Hypoxia significantly increased G9a protein level and G9a interacted with RUNX3 Runt domain, which led to increased methylation of RUNX3 at K129 and K171. This methylation inactivated transactivation activity of RUNX3 by reducing interactions with CBF beta and p300 cofactors, as well as reducing acetylation of RUNX3 by p300, which is involved in nucleocytoplasmic transport by importin-alpha 1. G9a-mediated methylation of RUNX3 under hypoxia promotes cancer cell proliferation by increasing cell cycle or cell division, while suppresses immune response and apoptosis, thereby promoting tumor growth during early tumorigenesis. Our results demonstrate the molecular mechanism of RUNX3 inactivation by G9a-mediated methylation for cell proliferation and antiapoptosis under hypoxia, which can be a therapeutic or preventive target to control tumor growth during early tumorigenesis. | Lee, Sun Hee; Hyeon, Do Young; Yoon, Soo-Hyun; Jeong, Ji-Hak; Han, Saeng-Myung; Jang, Ju-Won; Minh Phuong Nguyen; Chi, Xin-Zi; An, Sojin; Hyun, Kyung-gi; Jung, Hee-Jung; Song, Ji-Joon; Bae, Suk-Chul; Kim, Woo-Ho; Hwang, Daehee; Lee, You Mie | Kyungpook Natl Univ, Coll Pharm, Dept Mol Pathophysiol, Vessel Organ Interact Res Ctr,VOICE MRC, Daegu 41566, South Korea; Seoul Natl Univ, Sch Biol Sci, Seoul 08826, South Korea; Kyungpook Natl Univ, Sch Life Sci & Biotechnol, Daegu 41566, South Korea; Chungbuk Natl Univ, Sch Med, Inst Tumor Res, Dept Biochem, Cheongju 28644, South Korea; Korea Adv Inst Sci & Technol, Dept Biol Sci, KI BioCentury, Daejeon 34141, South Korea; DGIST, Inst Basic Sci, Ctr Plant Aging Res, Daegu 42988, South Korea; Seoul Natl Univ, Dept Pathol, Coll Med, Seoul 03080, South Korea; Hochiminh City Univ Food Ind, Ho Chi Minh City, Vietnam | Lee, Kyung-Soo/C-9016-2011; Song, Ji-Joon/C-1721-2011 | 58607352900; 57639005700; 34968837000; 55913671500; 36713424700; 35277093300; 55600460500; 7006495013; 56861679800; 57221297654; 55783704900; 7404786865; 7202714699; 57218663587; 7401880266; 8230508600 | daehee@snu.ac.kr;lym@knu.ac.kr; | CELL DEATH AND DIFFERENTIATION | CELL DEATH DIFFER | 1350-9047 | 1476-5403 | 28 | 4 | SCIE | BIOCHEMISTRY & MOLECULAR BIOLOGY;CELL BIOLOGY | 2021 | 12.073 | 7.6 | 1.55 | 2025-07-30 | 28 | 27 | GASTRIC-CANCER; TUMOR-SUPPRESSOR; PROTEIN; GENE; EXPRESSION; BINDING | Acetylation; Animals; Apoptosis; Carcinogenesis; Cell Hypoxia; Cell Line, Tumor; Cell Proliferation; Core Binding Factor Alpha 3 Subunit; DNA Methylation; Gene Expression Regulation, Neoplastic; Histocompatibility Antigens; Histone-Lysine N-Methyltransferase; Humans; Male; Mice; Mice, Inbred BALB C; Mice, Nude; Xenograft Model Antitumor Assays; E1A associated p300 protein; G9a protein; importin alpha1; karyopherin alpha; methyltransferase; transcription factor RUNX3; unclassified drug; EHMT2 protein, human; histocompatibility antigen; histone lysine methyltransferase; Runx3 protein, human; transcription factor RUNX3; acetylation; animal experiment; animal model; antiapoptosis; apoptosis; Article; cancer cell; carcinogenesis; cell cycle; cell division; cell proliferation; controlled study; embryo; female; gene expression; human; human cell; hypoxia; immune response; male; nonhuman; nucleocytoplasmic transport; protein domain; protein function; protein methylation; protein processing; protein protein interaction; protein stability; protein targeting; transactivation; animal; Bagg albino mouse; carcinogenesis; cell hypoxia; cell proliferation; DNA methylation; drug screening; gene expression regulation; genetics; metabolism; mouse; nude mouse; tumor cell line | English | 2021 | 2021-04 | 10.1038/s41418-020-00647-1 | 바로가기 | 바로가기 | 바로가기 | 바로가기 |
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