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Biodegradable PLGA Nanoparticles Restore Lysosomal Acidity and Protect Neural PC-12 Cells against Mitochondrial Toxicity

  • Jialiu Zeng*
    Jialiu Zeng
    Department of Biomedical Engineering, Boston University, Boston, Massachusetts 02215, United States
    *E-mail: [email protected]
    More by Jialiu Zeng
  • Andrew Martin
    Andrew Martin
    Department of Biomedical Engineering, Boston University, Boston, Massachusetts 02215, United States
  • Xue Han
    Xue Han
    Department of Biomedical Engineering, Boston University, Boston, Massachusetts 02215, United States
    More by Xue Han
  • Orian S. Shirihai
    Orian S. Shirihai
    Division of Endocrinology, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California 90095, United States
    Department of Medicine, Boston University School of Medicine, Boston, Massachusetts 02118, United States
  • , and 
  • Mark W. Grinstaff*
    Mark W. Grinstaff
    Department of Biomedical Engineering, Boston University, Boston, Massachusetts 02215, United States
    Department of Medicine, Boston University School of Medicine, Boston, Massachusetts 02118, United States
    Department of Chemistry, Boston University, Boston, Massachusetts 02215, United States
    *E-mail: [email protected]
Cite this: Ind. Eng. Chem. Res. 2019, 58, 31, 13910–13917
Publication Date (Web):July 16, 2019
https://doi.org/10.1021/acs.iecr.9b02003
Copyright © 2019 American Chemical Society

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    Abstract

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    Exposure of mitochondrial parkinsonian neurotoxin 1-methyl-4-phenylpyridinium ion (MPP+) to PC-12 cells results in significant cell death, decreases lysosomal acidity, and inhibits autophagic flux. Biodegradable poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) of ≈100 nm diameter localize to the lysosome, degrade, and subsequently release their acidic components to acidify the local lysosomal environment. The performance of PLGA NPs with different lysosomal pH modulating capabilities is investigated in PC-12 cells under MPP+ induced mitochondrial toxicity. PLGA NPs perform in a compositional dependent manner, where NPs with a higher glycolic acid to lactic acid ratio content degrade faster and yield greater degrees of lysosomal pH modulation as well as autophagic flux modulation in PC-12 cells under MPP+ insult. These results show that slight compositional changes of the polymeric NP give rise to differing degrees of lysosomal acidification in PC-12 cells and afford improved cellular degradative activity.

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    The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.iecr.9b02003.

    • Equations used to determine the amount of monomer needed to acidity PBS buffer; Figure S1, uptake of rhodamine labeled 50:50 PLGA, 75:25 PLGA, and PLA NPs in PC-12 cells was monitored using flow cytometry after 24 h of incubation; Figure S2, PLGA NPs pretreated for 16 h before MPP+ at (A) 50 μM, (B) 100 μM and (C) 1000 μM insult rescue PC-12 mitochondrial activity (PDF)

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Ferreira, Susan Ferro-Novick, Antonio Figueras, Riccardo Filadi, Nicoletta Filigheddu, Eduardo Filippi-Chiela, Giuseppe Filomeni, Gian Maria Fimia, Vittorio Fineschi, Francesca Finetti, Steven Finkbeiner, Edward A. Fisher, Paul B. Fisher, Flavio Flamigni, Steven J. Fliesler, Trude H. Flo, Ida Florance, Oliver Florey, Tullio Florio, Erika Fodor, Carlo Follo, Edward A. Fon, Antonella Forlino, Francesco Fornai, Paola Fortini, Anna Fracassi, Alessandro Fraldi, Brunella Franco, Rodrigo Franco, Flavia Franconi, Lisa B. Frankel, Scott L. Friedman, Leopold F. Fröhlich, Gema Frühbeck, Jose M. Fuentes, Yukio Fujiki, Naonobu Fujita, Yuuki Fujiwara, Mitsunori Fukuda, Simone Fulda, Luc Furic, Norihiko Furuya, Carmela Fusco, Michaela U. Gack, Lidia Gaffke, Sehamuddin Galadari, Alessia Galasso, Maria F. Galindo, Sachith Gallolu Kankanamalage, Lorenzo Galluzzi, Vincent Galy, Noor Gammoh, Boyi Gan, Ian G. Ganley, Feng Gao, Hui Gao, Minghui Gao, Ping Gao, Shou-Jiang Gao, Wentao Gao, Xiaobo Gao, Ana Garcera, Maria Noé Garcia, Verónica E. Garcia, Francisco García-Del Portillo, Vega Garcia-Escudero, Aracely Garcia-Garcia, Marina Garcia-Macia, Diana García-Moreno, Carmen Garcia-Ruiz, Patricia García-Sanz, Abhishek D. Garg, Ricardo Gargini, Tina Garofalo, Robert F. Garry, Nils C. Gassen, Damian Gatica, Liang Ge, Wanzhong Ge, Ruth Geiss-Friedlander, Cecilia Gelfi, Pascal Genschik, Ian E. Gentle, Valeria Gerbino, Christoph Gerhardt, Kyla Germain, Marc Germain, David A. Gewirtz, Elham Ghasemipour Afshar, Saeid Ghavami, Alessandra Ghigo, Manosij Ghosh, Georgios Giamas, Claudia Giampietri, Alexandra Giatromanolaki, Gary E. Gibson, Spencer B. Gibson, Vanessa Ginet, Edward Giniger, Carlotta Giorgi, Henrique Girao, Stephen E. Girardin, Mridhula Giridharan, Sandy Giuliano, Cecilia Giulivi, Sylvie Giuriato, Julien Giustiniani, Alexander Gluschko, Veit Goder, Alexander Goginashvili, Jakub Golab, David C. Goldstone, Anna Golebiewska, Luciana R. Gomes, Rodrigo Gomez, Rubén Gómez-Sánchez, Maria Catalina Gomez-Puerto, Raquel Gomez-Sintes, Qingqiu Gong, Felix M. Goni, Javier González-Gallego, Tomas Gonzalez-Hernandez, Rosa A. Gonzalez-Polo, Jose A. Gonzalez-Reyes, Patricia González-Rodríguez, Ing Swie Goping, Marina S. Gorbatyuk, Nikolai V. Gorbunov, Kıvanç Görgülü, Roxana M. Gorojod, Sharon M. Gorski, Sandro Goruppi, Cecilia Gotor, Roberta A. Gottlieb, Illana Gozes, Devrim Gozuacik, Martin Graef, Markus H. Gräler, Veronica Granatiero, Daniel Grasso, Joshua P. Gray, Douglas R. Green, Alexander Greenhough, Stephen L. Gregory, Edward F. Griffin, Mark W. Grinstaff, Frederic Gros, Charles Grose, Angelina S. Gross, Florian Gruber, Paolo Grumati, Tilman Grune, Xueyan Gu, Jun-Lin Guan, Carlos M. Guardia, Kishore Guda, Flora Guerra, Consuelo Guerri, Prasun Guha, Carlos Guillén, Shashi Gujar, Anna Gukovskaya, Ilya Gukovsky, Jan Gunst, Andreas Günther, Anyonya R. Guntur, Chuanyong Guo, Chun Guo, Hongqing Guo, Lian-Wang Guo, Ming Guo, Pawan Gupta, Shashi Kumar Gupta, Swapnil Gupta, Veer Bala Gupta, Vivek Gupta, Asa B. Gustafsson, David D. Gutterman, Ranjitha H.B., Annakaisa Haapasalo, James E. Haber, Aleksandra Hać, Shinji Hadano, Anders J. Hafrén, Mansour Haidar, Belinda S. Hall, Gunnel Halldén, Anne Hamacher-Brady, Andrea Hamann, Maho Hamasaki, Weidong Han, Malene Hansen, Phyllis I.  Hanson, Zijian Hao, Masaru Harada, Ljubica Harhaji-Trajkovic, Nirmala Hariharan, Nigil Haroon, James Harris, Takafumi Hasegawa, Noor Hasima Nagoor, Jeffrey A. Haspel, Volker Haucke, Wayne D. Hawkins, Bruce A. Hay, Cole M. Haynes, Soren B. Hayrabedyan, Thomas S. Hays, Congcong He, Qin He, Rong-Rong He, You-Wen He, Yu-Ying He, Yasser Heakal, Alexander M. Heberle, J. Fielding Hejtmancik, Gudmundur Vignir  Helgason, Vanessa Henkel, Marc Herb, Alexander Hergovich, Anna Herman-Antosiewicz, Agustín Hernández, Carlos Hernandez, Sergio Hernandez-Diaz, Virginia Hernandez-Gea, Amaury Herpin, Judit Herreros, Javier H. Hervás, Daniel Hesselson, Claudio Hetz, Volker T. Heussler, Yujiro Higuchi, Sabine Hilfiker, Joseph A. Hill, William S. Hlavacek, Emmanuel A. Ho, Idy H.T. Ho, Philip Wing-Lok Ho, Shu-Leong Ho, Wan Yun Ho, G. Aaron Hobbs, Mark Hochstrasser, Peter H.M. Hoet, Daniel Hofius, Paul Hofman, Annika Höhn, Carina I. Holmberg, Jose R. Hombrebueno, Chang-Won Hong, Yi-Ren Hong, Lora V. Hooper, Thorsten Hoppe, Rastislav Horos, Yujin Hoshida, I-Lun Hsin, Hsin-Yun Hsu, Bing Hu, Dong Hu, Li-Fang Hu, Ming Chang Hu, Ronggui Hu, Wei Hu, Yu-Chen Hu, Zhuo-Wei Hu, Fang Hua, Jinlian Hua, Yingqi Hua, Chongmin Huan, Canhua Huang, Chuanshu Huang, Chuanxin Huang, Chunling Huang, Haishan Huang, Kun Huang, Michael L.H. Huang, Rui Huang, Shan Huang, Tianzhi Huang, Xing Huang, Yuxiang Jack Huang, Tobias B. Huber, Virginie Hubert, Christian A. Hubner, Stephanie M. Hughes, William E. Hughes, Magali Humbert, Gerhard Hummer, James H. Hurley, Sabah Hussain, Salik Hussain, Patrick J. Hussey, Martina Hutabarat, Hui-Yun Hwang, Seungmin Hwang, Antonio Ieni, Fumiyo Ikeda, Yusuke Imagawa, Yuzuru Imai, Carol Imbriano, Masaya Imoto, Denise M. Inman, Ken Inoki, Juan Iovanna, Renato V. Iozzo, Giuseppe Ippolito, Javier E. Irazoqui, Pablo Iribarren, Mohd Ishaq, Makoto Ishikawa, Nestor Ishimwe, Ciro Isidoro, Nahed Ismail, Shohreh Issazadeh-Navikas, Eisuke Itakura, Daisuke Ito, Davor Ivankovic, Saška Ivanova, Anand Krishnan V. Iyer, José M. Izquierdo, Masanori Izumi, Marja Jäättelä, Majid Sakhi Jabir, William T. Jackson, Nadia Jacobo-Herrera, Anne-Claire Jacomin, Elise Jacquin, Pooja Jadiya, Hartmut Jaeschke, Chinnaswamy Jagannath, Arjen J. Jakobi, Johan Jakobsson, Bassam Janji, Pidder Jansen-Dürr, Patric J. Jansson, Jonathan Jantsch, Sławomir Januszewski, Alagie Jassey, Steve Jean, Hélène Jeltsch-David, Pavla Jendelova, Andreas Jenny, Thomas E. Jensen, Niels Jessen, Jenna L. Jewell, Jing Ji, Lijun Jia, Rui Jia, Liwen Jiang, Qing Jiang, Richeng Jiang, Teng Jiang, Xuejun Jiang, Yu Jiang, Maria Jimenez-Sanchez, Eun-Jung Jin, Fengyan Jin, Hongchuan Jin, Li Jin, Luqi Jin, Meiyan Jin, Si Jin, Eun-Kyeong Jo, Carine Joffre, Terje Johansen, Gail V.W. Johnson, Simon A. Johnston, Eija Jokitalo, Mohit Kumar Jolly, Leo A.B. Joosten, Joaquin Jordan, Bertrand Joseph, Dianwen Ju, Jeong-Sun Ju, Jingfang Ju, Esmeralda Juárez, Delphine Judith, Gábor Juhász, Youngsoo Jun, Chang Hwa Jung, Sung-Chul Jung, Yong Keun Jung, Heinz Jungbluth, Johannes Jungverdorben, Steffen Just, Kai Kaarniranta, Allen Kaasik, Tomohiro Kabuta, Daniel Kaganovich, Alon Kahana, Renate Kain, Shinjo Kajimura, Maria Kalamvoki, Manjula Kalia, Danuta S. Kalinowski, Nina Kaludercic, Ioanna Kalvari, Joanna Kaminska, Vitaliy O. Kaminskyy, Hiromitsu Kanamori, Keizo Kanasaki, Chanhee Kang, Rui Kang, Sang Sun Kang, Senthilvelrajan Kaniyappan, Tomotake Kanki, Thirumala-Devi Kanneganti, Anumantha G. Kanthasamy, Arthi Kanthasamy, Marc Kantorow, Orsolya Kapuy, Michalis V. Karamouzis, Md. Razaul Karim, Parimal Karmakar, Rajesh G. Katare, Masaru Kato, Stefan H.E. Kaufmann, Anu Kauppinen, Gur P. Kaushal, Susmita Kaushik, Kiyoshi Kawasaki, Kemal Kazan, Po-Yuan Ke, Damien J. Keating, Ursula Keber, John H. Kehrl, Kate E. Keller, Christian W. Keller, Jongsook Kim Kemper, Candia M. Kenific, Oliver Kepp, Stephanie Kermorgant, Andreas Kern, Robin Ketteler, Tom G. Keulers, Boris Khalfin, Hany Khalil, Bilon Khambu, Shahid Y. Khan, Vinoth Kumar Megraj Khandelwal, Rekha Khandia, Widuri Kho, Noopur V. Khobrekar, Sataree Khuansuwan, Mukhran Khundadze, Samuel A. Killackey, Dasol Kim, Deok Ryong Kim, Do-Hyung Kim, Dong-Eun Kim, Eun Young Kim, Eun-Kyoung Kim, Hak-Rim Kim, Hee-Sik Kim, Hyung-Ryong Kim, Jeong Hun Kim, Jin Kyung Kim, Jin-Hoi Kim, Joungmok Kim, Ju Hwan Kim, Keun Il Kim, Peter K. Kim, Seong-Jun Kim, Scot R. Kimball, Adi Kimchi, Alec C. Kimmelman, Tomonori Kimura, Matthew A. King, Kerri J. Kinghorn, Conan G. Kinsey, Vladimir Kirkin, Lorrie A. Kirshenbaum, Sergey L. Kiselev, Shuji Kishi, Katsuhiko Kitamoto, Yasushi Kitaoka, Kaio Kitazato, Richard N. Kitsis, Josef T. Kittler, Ole Kjaerulff, Peter S. Klein, Thomas Klopstock, Jochen Klucken, Helene Knævelsrud, Roland L. Knorr, Ben C.B. Ko, Fred Ko, Jiunn-Liang Ko, Hotaka Kobayashi, Satoru Kobayashi, Ina Koch, Jan C. Koch, Ulrich Koenig, Donat Kögel, Young Ho Koh, Masato Koike, Sepp D. Kohlwein, Nur M. Kocaturk, Masaaki Komatsu, Jeannette König, Toru Kono, Benjamin T. Kopp, Tamas Korcsmaros, Gözde Korkmaz, Viktor I. Korolchuk, Mónica Suárez Korsnes, Ali Koskela, Janaiah Kota, Yaichiro Kotake, Monica L. Kotler, Yanjun Kou, Michael I. Koukourakis, Evangelos Koustas, Attila L. Kovacs, Tibor Kovács, Daisuke Koya, Tomohiro Kozako, Claudine Kraft, Dimitri Krainc, Helmut Krämer, Anna D. Krasnodembskaya, Carole Kretz-Remy, Guido Kroemer, Nicholas T. Ktistakis, Kazuyuki Kuchitsu, Sabine Kuenen, Lars Kuerschner, Thomas Kukar, Ajay Kumar, Ashok Kumar, Deepak Kumar, Dhiraj Kumar, Sharad Kumar, Shinji Kume, Caroline Kumsta, Chanakya N. Kundu, Mondira Kundu, Ajaikumar B. Kunnumakkara, Lukasz Kurgan, Tatiana G. Kutateladze, Ozlem Kutlu, SeongAe Kwak, Ho Jeong Kwon, Taeg Kyu Kwon, Yong Tae Kwon, Irene Kyrmizi, Albert La Spada, Patrick Labonté, Sylvain Ladoire, Ilaria Laface, Frank Lafont, Diane C. Lagace, Vikramjit Lahiri, Zhibing Lai, Angela S. Laird, Aparna Lakkaraju, Trond Lamark, Sheng-Hui Lan, Ane Landajuela, Darius J. R. Lane, Jon D. Lane, Charles H. Lang, Carsten Lange, Ülo Langel, Rupert Langer, Pierre Lapaquette, Jocelyn Laporte, Nicholas F. LaRusso, Isabel Lastres-Becker, Wilson Chun Yu Lau, Gordon W. Laurie, Sergio Lavandero, Betty Yuen Kwan Law, Helen Ka-wai Law, Rob Layfield, Weidong Le, Herve Le Stunff, Alexandre Y. Leary, Jean-Jacques Lebrun, Lionel Y.W. Leck, Jean-Philippe Leduc-Gaudet, Changwook Lee, Chung-Pei Lee, Da-Hye Lee, Edward B. Lee, Erinna F. Lee, Gyun Min Lee, He-Jin Lee, Heung Kyu Lee, Jae Man Lee, Jason S. Lee, Jin-A Lee, Joo-Yong Lee, Jun Hee Lee, Michael Lee, Min Goo Lee, Min Jae Lee, Myung-Shik Lee, Sang Yoon Lee, Seung-Jae Lee, Stella Y. Lee, Sung Bae Lee, Won Hee Lee, Ying-Ray Lee, Yong-ho Lee, Youngil Lee, Christophe Lefebvre, Renaud Legouis, Yu L. Lei, Yuchen Lei, Sergey Leikin, Gerd Leitinger, Leticia Lemus, Shuilong Leng, Olivia Lenoir, Guido Lenz, Heinz Josef Lenz, Paola Lenzi, Yolanda León, Andréia M. Leopoldino, Christoph Leschczyk, Stina Leskelä, Elisabeth Letellier, Chi-Ting Leung, Po Sing Leung, Jeremy S. Leventhal, Beth Levine, Patrick A. Lewis, Klaus Ley, Bin Li, Da-Qiang Li, Jianming Li, Jing Li, Jiong Li, Ke Li, Liwu Li, Mei Li, Min Li, Min Li, Ming Li, Mingchuan Li, Pin-Lan Li, Ming-Qing Li, Qing Li, Sheng Li, Tiangang Li, Wei Li, Wenming Li, Xue Li, Yi-Ping Li, Yuan Li, Zhiqiang Li, Zhiyong Li, Zhiyuan Li, Jiqin Lian, Chengyu Liang, Qiangrong Liang, Weicheng Liang, Yongheng Liang, YongTian Liang, Guanghong Liao, Lujian Liao, Mingzhi Liao, Yung-Feng Liao, Mariangela Librizzi, Pearl P. Y. Lie, Mary A. Lilly, Hyunjung J. Lim, Thania R.R. Lima, Federica Limana, Chao Lin, Chih-Wen Lin, Dar-Shong Lin, Fu-Cheng Lin, Jiandie D. Lin, Kurt M. Lin, Kwang-Huei Lin, Liang-Tzung Lin, Pei-Hui Lin, Qiong Lin, Shaofeng Lin, Su-Ju Lin, Wenyu Lin, Xueying Lin, Yao-Xin Lin, Yee-Shin Lin, Rafael Linden, Paula Lindner, Shuo-Chien Ling, Paul Lingor, Amelia K. Linnemann, Yih-Cherng Liou, Marta M. Lipinski, Saška Lipovšek, Vitor A. Lira, Natalia Lisiak, Paloma B. Liton, Chao Liu, Ching-Hsuan Liu, Chun-Feng Liu, Cui Hua Liu, Fang Liu, Hao Liu, Hsiao-Sheng Liu, Hua-feng Liu, Huifang Liu, Jia Liu, Jing Liu, Julia Liu, Leyuan Liu, Longhua Liu, Meilian Liu, Qin Liu, Wei Liu, Wende Liu, Xiao-Hong Liu, Xiaodong Liu, Xingguo Liu, Xu Liu, Xuedong Liu, Yanfen Liu, Yang Liu, Yang Liu, Yueyang Liu, Yule Liu, J. Andrew Livingston, Gerard Lizard, Jose M. Lizcano, Senka Ljubojevic-Holzer, Matilde E. LLeonart, David Llobet-Navàs, Alicia Llorente, Chih Hung Lo, Damián Lobato-Márquez, Qi Long, Yun Chau Long, Ben Loos, Julia A. Loos, Manuela G. López, Guillermo López-Doménech, José Antonio López-Guerrero, Ana T. López-Jiménez, Óscar López-Pérez, Israel López-Valero, Magdalena J. Lorenowicz, Mar Lorente, Peter Lorincz, Laura Lossi, Sophie Lotersztajn, Penny E. Lovat, Jonathan F. Lovell, Alenka Lovy, Péter Lőw, Guang Lu, Haocheng Lu, Jia-Hong Lu, Jin-Jian Lu, Mengji Lu, Shuyan Lu, Alessandro Luciani, John M. Lucocq, Paula Ludovico, Micah A. Luftig, Morten Luhr, Diego Luis-Ravelo, Julian J. Lum, Liany Luna-Dulcey, Anders H. Lund, Viktor K. Lund, Jan D. Lünemann, Patrick Lüningschrör, Honglin Luo, Rongcan Luo, Shouqing Luo, Zhi Luo, Claudio Luparello, Bernhard Lüscher, Luan Luu, Alex Lyakhovich, Konstantin G. Lyamzaev, Alf Håkon Lystad, Lyubomyr Lytvynchuk, Alvin C. Ma, Changle Ma, Mengxiao Ma, Ning-Fang Ma, Quan-Hong Ma, Xinliang Ma, Yueyun Ma, Zhenyi Ma, Ormond A. MacDougald, Fernando Macian, Gustavo C. MacIntosh, Jeffrey P. MacKeigan, Kay F. Macleod, Sandra Maday, Frank Madeo, Muniswamy Madesh, Tobias Madl, Julio Madrigal-Matute, Akiko Maeda, Yasuhiro Maejima, Marta Magarinos, Poornima Mahavadi, Emiliano Maiani, Kenneth Maiese, Panchanan Maiti, Maria Chiara Maiuri, Barbara Majello, Michael B. Major, Elena Makareeva, Fayaz Malik, Karthik Mallilankaraman, Walter Malorni, Alina Maloyan, Najiba Mammadova, Gene Chi Wai Man, Federico Manai, Joseph D. Mancias, Eva-Maria Mandelkow, Michael A. Mandell, Angelo A. Manfredi, Masoud H. Manjili, Ravi Manjithaya, Patricio Manque, Bella B. Manshian, Raquel Manzano, Claudia Manzoni, Kai Mao, Cinzia Marchese, Sandrine Marchetti, Anna Maria Marconi, Fabrizio Marcucci, Stefania Mardente, Olga A. Mareninova, Marta Margeta, Muriel Mari, Sara Marinelli, Oliviero Marinelli, Guillermo Mariño, Sofia Mariotto, Richard S. Marshall, Mark R. Marten, Sascha Martens, Alexandre P.J. Martin, Katie R. Martin, Sara Martin, Shaun Martin, Adrián Martín-Segura, Miguel A. Martín-Acebes, Inmaculada Martin-Burriel, Marcos Martin-Rincon, Paloma Martin-Sanz, José A. Martina, Wim Martinet, Aitor Martinez, Ana Martinez, Jennifer Martinez, Moises Martinez Velazquez, Nuria Martinez-Lopez, Marta Martinez-Vicente, Daniel O. Martins, Joilson O. Martins, Waleska K. Martins, Tania Martins-Marques, Emanuele Marzetti, Shashank Masaldan, Celine Masclaux-Daubresse, Douglas G. Mashek, Valentina Massa, Lourdes Massieu, Glenn R. Masson, Laura Masuelli, Anatoliy I. Masyuk, Tetyana V. Masyuk, Paola Matarrese, Ander Matheu, Satoaki Matoba, Sachiko Matsuzaki, Pamela Mattar, Alessandro Matte, Domenico Mattoscio, José L. Mauriz, Mario Mauthe, Caroline Mauvezin, Emanual Maverakis, Paola Maycotte, Johanna Mayer, Gianluigi Mazzoccoli, Cristina Mazzoni, Joseph R. Mazzulli, Nami McCarty, Christine McDonald, Mitchell R. McGill, Sharon L. McKenna, BethAnn McLaughlin, Fionn McLoughlin, Mark A. McNiven, Thomas G. McWilliams, Fatima Mechta-Grigoriou, Tania Catarina Medeiros, Diego L. Medina, Lynn A. Megeney, Klara Megyeri, Maryam Mehrpour, Jawahar L. Mehta, Alfred J. Meijer, Annemarie H. Meijer, Jakob Mejlvang, Alicia Meléndez, Annette Melk, Gonen Memisoglu, Alexandrina F. Mendes, Delong Meng, Fei Meng, Tian Meng, Rubem Menna-Barreto, Manoj B. Menon, Carol Mercer, Anne E. Mercier, Jean-Louis Mergny, Adalberto Merighi, Seth D. Merkley, Giuseppe Merla, Volker Meske, Ana Cecilia Mestre, Shree Padma Metur, Christian Meyer, Hemmo Meyer, Wenyi Mi, Jeanne Mialet-Perez, Junying Miao, Lucia Micale, Yasuo Miki, Enrico Milan, Małgorzata Milczarek, Dana L. Miller, Samuel I. Miller, Silke Miller, Steven W. Millward, Ira Milosevic, Elena A. Minina, Hamed Mirzaei, Hamid Reza Mirzaei, Mehdi Mirzaei, Amit Mishra, Nandita Mishra, Paras Kumar Mishra, Maja Misirkic Marjanovic, Roberta Misasi, Amit Misra, Gabriella Misso, Claire Mitchell, Geraldine Mitou, Tetsuji Miura, Shigeki Miyamoto, Makoto Miyazaki, Mitsunori Miyazaki, Taiga Miyazaki, Keisuke Miyazawa, Noboru Mizushima, Trine H. Mogensen, Baharia Mograbi, Reza Mohammadinejad, Yasir Mohamud, Abhishek Mohanty, Sipra Mohapatra, Torsten Möhlmann, Asif Mohmmed, Anna Moles, Kelle H. Moley, Maurizio Molinari, Vincenzo Mollace, Andreas Buch Møller, Bertrand Mollereau, Faustino Mollinedo, Costanza Montagna, Mervyn J. Monteiro, Andrea Montella, L. Ruth Montes, Barbara Montico, Vinod K. Mony, Giacomo Monzio Compagnoni, Michael N. Moore, Mohammad A. Moosavi, Ana L. Mora, Marina Mora, David Morales-Alamo, Rosario Moratalla, Paula I. Moreira, Elena Morelli, Sandra Moreno, Daniel Moreno-Blas, Viviana Moresi, Benjamin Morga, Alwena H. Morgan, Fabrice Morin, Hideaki Morishita, Orson L. Moritz, Mariko Moriyama, Yuji Moriyasu, Manuela Morleo, Eugenia Morselli, Jose F. Moruno-Manchon, Jorge Moscat, Serge Mostowy, Elisa Motori, Andrea Felinto Moura, Naima Moustaid-Moussa, Maria Mrakovcic, Gabriel Muciño-Hernández, Anupam Mukherjee, Subhadip Mukhopadhyay, Jean M. Mulcahy Levy, Victoriano Mulero, Sylviane Muller, Christian Münch, Ashok Munjal, Pura Munoz-Canoves, Teresa Muñoz-Galdeano, Christian Münz, Tomokazu Murakawa, Claudia Muratori, Brona M. Murphy, J. Patrick Murphy, Aditya Murthy, Timo T. Myöhänen, Indira U. Mysorekar, Jennifer Mytych, Seyed Mohammad Nabavi, Massimo Nabissi, Péter Nagy, Jihoon Nah, Aimable Nahimana, Ichiro Nakagawa, Ken Nakamura, Hitoshi Nakatogawa, Shyam S. Nandi, Meera Nanjundan, Monica Nanni, Gennaro Napolitano, Roberta Nardacci, Masashi Narita, Melissa Nassif, Ilana Nathan, Manabu Natsumeda, Ryno J. Naude, Christin Naumann, Olaia Naveiras, Fatemeh Navid, Steffan T. Nawrocki, Taras Y. Nazarko, Francesca Nazio, Florentina Negoita, Thomas Neill, Amanda L. Neisch, Luca M. Neri, Mihai G. Netea, Patrick Neubert, Thomas P. Neufeld, Dietbert Neumann, Albert Neutzner, Phillip T. Newton, Paul A. Ney, Ioannis P. Nezis, Charlene C.W. Ng, Tzi Bun Ng, Hang T. T. Nguyen, Long T. Nguyen, Hong-Min Ni, Clíona Ní Cheallaigh, Zhenhong Ni, M. Celeste Nicolao, Francesco Nicoli, Manuel Nieto-Diaz, Per Nilsson, Shunbin Ning, Rituraj Niranjan, Hiroshi Nishimune, Mireia Niso-Santano, Ralph A. Nixon, Annalisa Nobili, Clevio Nobrega, Takeshi Noda, Uxía Nogueira-Recalde, Trevor M. Nolan, Ivan Nombela, Ivana Novak, Beatriz Novoa, Takashi Nozawa, Nobuyuki Nukina, Carmen Nussbaum-Krammer, Jesper Nylandsted, Tracey R. O’Donovan, Seónadh M. O’Leary, Eyleen J. O’Rourke, Mary P. O’Sullivan, Timothy E. O’Sullivan, Salvatore Oddo, Ina Oehme, Michinaga Ogawa, Eric Ogier-Denis, Margret H. Ogmundsdottir, Besim Ogretmen, Goo Taeg Oh, Seon-Hee Oh, Young J. Oh, Takashi Ohama, Yohei Ohashi, Masaki Ohmuraya, Vasileios Oikonomou, Rani Ojha, Koji Okamoto, Hitoshi Okazawa, Masahide Oku, Sara Oliván, Jorge M. A. Oliveira, Michael Ollmann, James A. Olzmann, Shakib Omari, M. Bishr Omary, Gizem Önal, Martin Ondrej, Sang-Bing Ong, Sang-Ging Ong, Anna Onnis, Juan A. Orellana, Sara Orellana-Muñoz, Maria Del Mar Ortega-Villaizan, Xilma R. Ortiz-Gonzalez, Elena Ortona, Heinz D. Osiewacz, Abdel-Hamid K. Osman, Rosario Osta, Marisa S. 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