TY - GEN A1 - Künzel, Stephan R. A1 - Hoffmann, Maximilian A1 - Weber, Silvio A1 - Künzel, Karolina A1 - Kämmerer, Susanne A1 - Günscht, Mario A1 - Klapproth, Erik A1 - Rausch, Johanna S. E. A1 - Sadek, Mirna S. A1 - Kolanowski, Tomasz A1 - Meyer-Roxlau, Stefanie A1 - Piorkowski, Christopher A1 - Tugtekin, Sems M. A1 - Rose-John, Stefan A1 - Yin, Xiaoke A1 - Mayr, Manuel A1 - Kuhlmann, Jan Dominik A1 - Wimberger, Pauline A1 - Grützmann, Konrad A1 - Herzog, Natalie A1 - Küpper, Jan-Heiner A1 - O’Reilly, Molly A1 - Kabir, S. Nashitha A1 - Sommerfeld, Laura C. A1 - Guan, Kaomei A1 - Wielockx, Ben A1 - Fabritz, Larissa A1 - Nattel, Stanley A1 - Ravens, Ursula A1 - Dobrev, Dobromir A1 - Wagner, Michael A1 - El-Armouche, Ali T1 - Diminished PLK2 Induces Cardiac Fibrosis and Promotes Atrial Fibrillation T2 - Circulation Research N2 - Rationale: Fibrosis promotes the maintenance of atrial fibrillation (AF), making it resistant to therapy. Improved understanding of the molecular mechanisms leading to atrial fibrosis will open new pathways toward effective antifibrotic therapies. Objective: This study aims to decipher the mechanistic interplay between PLK2 (polo-like kinase 2) and the profibrotic cytokine OPN (osteopontin) in the pathogenesis of atrial fibrosis and AF. Methods and Results: Atrial PLK2 mRNA expression was 10-fold higher in human fibroblasts than in cardiomyocytes. Compared with sinus rhythm, right atrial appendages and isolated right atrial fibroblasts from patients with AF showed downregulation of PLK2 mRNA and protein, along with increased PLK2 promotor methylation. Genetic deletion as well as pharmacological inhibition of PLK2 induced profibrotic phenotype conversion in cardiac fibroblasts and led to a striking de novo secretion of OPN. Accordingly, PLK2-deficient (PLK2 knockout) mice showed cardiac fibrosis and were prone to experimentally induced AF. In line with these findings, OPN plasma levels were significantly higher only in patients with AF with atrial low-voltage zones (surrogates of fibrosis) compared with sinus rhythm controls. Mechanistically, we identified ERK1/2 as the relevant downstream mediator of PLK2 leading to increased OPN expression. Finally, oral treatment with the clinically available drug mesalazine, known to inhibit ERK1/2, prevented cardiac OPN overexpression and reversed the pathological PLK2 knockout phenotype in PLK2 knockout mice. Conclusions: Abnormal PLK2/ERK1/2/OPN axis function critically contributes to AF-related atrial fibrosis, suggesting reinforcing PLK2 activity and/or OPN inhibition as innovative targets to prevent fibrosis progression in AF. Mesalazine derivatives may be used as lead compounds for the development of novel anti-AF agents targeting fibrosis. KW - atrial fibrillation KW - fibroblasts KW - fibrosis KW - mesalamine KW - osteopontin Y1 - 2021 UR - https://www.ahajournals.org/doi/full/10.1161/CIRCRESAHA.121.319425 U6 - https://doi.org/10.1161/CIRCRESAHA.121.319425 SN - 1524-4571 SN - 0009-7330 VL - 129 IS - 8 SP - 804 EP - 820 ER - TY - GEN A1 - Fischer, Thomas A1 - Marchetti-Deschmann, Martina A1 - Assis, Ana Cristina A1 - Elad, Michal Levin A1 - Algarra, Manuel A1 - Barac, Marko A1 - Bogdanovic Radovic, Iva A1 - Cicconi, Flavio A1 - Claes, Britt A1 - Frascione, Nunzianda A1 - George, Sony A1 - Guedes, Alexandra A1 - Heaton, Cameron A1 - Heeren, Ron A1 - Lasic, Violeta A1 - Lerma, José Luis A1 - Valle Martinez de Yuso Garcia, Maria del A1 - Nosko, Martin A1 - O'Hara, John A1 - Oshina, Ilze A1 - Palucci, Antonio A1 - Pawlaczyk, Aleksandra A1 - Pospíšková, Kristýna A1 - de Puit, Marcel A1 - Radodic, Ksenija A1 - Rēpele, Māra A1 - Ristova, Mimoza A1 - Romolo, Francesco Saverio A1 - Šafařík, Ivo A1 - Siketic, Zdravko A1 - Spigulis, Janis A1 - Szynkowska-Jozwik, Malgorzata Iwona A1 - Tsiatsiuyeu, Andrei A1 - Vella, Joanna A1 - Dawson, Lorna A1 - Rödiger, Stefan A1 - Francese, Simona T1 - Profiling and imaging of forensic evidence – A pan-European forensic round robin study part 1: Document forgery T2 - Science & Justice Y1 - 2022 U6 - https://doi.org/10.1016/j.scijus.2022.06.001 SN - 1876-4452 SN - 1355-0306 VL - 62 IS - 4 SP - 433 EP - 447 ER - TY - GEN A1 - Neyret, Margot A1 - Le Provost, Gaëtane A1 - Boesing, Andrea Larissa A1 - Schneider, Florian D. A1 - Baulechner, Dennis A1 - Bergmann, Joana A1 - Vries, Franciska T. de A1 - Fiore-Donno, Anna Maria A1 - Geisen, Stefan A1 - Goldmann, Kezia A1 - Merges, Anna A1 - Saifutdinov, Ruslan A. A1 - Simons, Nadja K. A1 - Tobias, Joseph A. A1 - Zaitsev, Andrey S. A1 - Gossner, Martin M. A1 - Jung, Kirsten A1 - Kandeler, Ellen A1 - Krauss, Jochen A1 - Penone, Caterina A1 - Schloter, Michael A1 - Schulz, Stefanie A1 - Staab, Michael A1 - Wolters, Volkmar A1 - Apostolakis, Antonios A1 - Birkhofer, Klaus A1 - Boch, Steffen A1 - Boeddinghaus, Runa S. A1 - Bolliger, Ralph A1 - Bonkowski, Michael A1 - Buscot, François A1 - Dumack, Kenneth A1 - Fischer, Markus A1 - Gan, Huei Ying A1 - Heinze, Johannes A1 - Hölzel, Norbert A1 - John, Katharina A1 - Klaus, Valentin H. A1 - Kleinebecker, Till A1 - Marhan, Sven A1 - Müller, Jörg A1 - Renner, Swen C. A1 - Rillig, Matthias C. A1 - Schenk, Noëlle V. A1 - Schöning, Ingo A1 - Schrumpf, Marion A1 - Seibold, Sebastian A1 - Socher, Stephanie A. A1 - Solly, Emily F. A1 - Teuscher, Miriam A1 - Kleunen, Mark van A1 - Wubet, Tesfaye A1 - Manning, Peter T1 - A slow-fast trait continuum at the whole community level in relation to land-use intensification T2 - Nature Communications N2 - AbstractOrganismal functional strategies form a continuum from slow- to fast-growing organisms, in response to common drivers such as resource availability and disturbance. However, whether there is synchronisation of these strategies at the entire community level is unclear. Here, we combine trait data for 2800 above- and belowground taxa from 14 trophic guilds spanning a disturbance and resource availability gradient in German grasslands. The results indicate that most guilds consistently respond to these drivers through both direct and trophically mediated effects, resulting in a ‘slow-fast’ axis at the level of the entire community. Using 15 indicators of carbon and nutrient fluxes, biomass production and decomposition, we also show that fast trait communities are associated with faster rates of ecosystem functioning. These findings demonstrate that ‘slow’ and ‘fast’ strategies can be manifested at the level of whole communities, opening new avenues of ecosystem-level functional classification. KW - General Physics and Astronomy KW - General Biochemistry KW - General Chemistry KW - Multidisciplinary KW - Genetics and Molecular Biology Y1 - 2024 U6 - https://doi.org/10.1038/s41467-024-45113-5 SN - 2041-1723 VL - 15 IS - 1 ER - TY - GEN A1 - John, Stefan A1 - Kosiol, Jens A1 - Lambers, Leen A1 - Taentzer, Gabriele T1 - A graph-based framework for model-driven optimization facilitating impact analysis of mutation operator properties T2 - Software and Systems Modeling N2 - Optimization problems in software engineering typically deal with structures as they occur in the design and maintenance of software systems. In model-driven optimization (MDO), domain-specific models are used to represent these structures while evolutionary algorithms are often used to solve optimization problems. However, designing appropriate models and evolutionary algorithms to represent and evolve structures is not always straightforward. Domain experts often need deep knowledge of how to configure an evolutionary algorithm. This makes the use of model-driven meta-heuristic search difficult and expensive. We present a graph-based framework for MDO that identifies and clarifies core concepts and relies on mutation operators to specify evolutionary change. This framework is intended to help domain experts develop and study evolutionary algorithms based on domain-specific models and operators. In addition, it can help in clarifying the critical factors for conducting reproducible experiments in MDO. Based on the framework, we are able to take a first step toward identifying and studying important properties of evolutionary operators in the context of MDO. As a showcase, we investigate the impact of soundness and completeness at the level of mutation operator sets on the effectiveness and efficiency of evolutionary algorithms. KW - Search-Based Software Engineering KW - Model-Driven Engineering KW - Evolutionary Computation Y1 - 2023 U6 - https://doi.org/10.1007/s10270-022-01078-x SN - 1619-1374 VL - 22 SP - 1281 EP - 1318 ER - TY - GEN A1 - Buchanan, Erin M. A1 - Lewis, Savannah C. A1 - Paris, Bastien A1 - Forscher, Patrick S. A1 - Pavlacic, Jeffrey M. A1 - Beshears, Julie E. A1 - Drexler, Shira Meir A1 - Gourdon-Kanhukamwe, Amélie A1 - Mallik, Peter R A1 - Silan, Miguel Alejandro A. A1 - Miller, Jeremy K. A1 - IJzerman, Hans A1 - Moshontz, Hannah A1 - Beaudry, Jennifer L. A1 - Suchow, Jordan W. A1 - Chartier, Christopher R. A1 - Coles, Nicholas A. A1 - Sharifian, MohammadHasan A1 - Todsen, Anna Louise A1 - Levitan, Carmel A. A1 - Azevedo, Flávio A1 - Legate, Nicole A1 - Heller, Blake A1 - Rothman, Alexander J. A1 - Dorison, Charles A. A1 - Gill, Brian P. A1 - Wang, Ke A1 - Rees, Vaughan W. A1 - Gibbs, Nancy A1 - Goldenberg, Amit A1 - Thi Nguyen, Thuy-vy A1 - Gross, James J. A1 - Kaminski, Gwenaêl A1 - von Bastian, Claudia C. A1 - Paruzel-Czachura, Mariola A1 - Mosannenzadeh, Farnaz A1 - Azouaghe, Soufian A1 - Bran, Alexandre A1 - Ruiz-Fernandez, Susana A1 - Santos, Anabela Caetano A1 - Reggev, Niv A1 - Zickfeld, Janis H. A1 - Akkas, Handan A1 - Pantazi, Myrto A1 - Ropovik, Ivan A1 - Korbmacher, Max A1 - Arriaga, Patrícia A1 - Gjoneska, Biljana A1 - Warmelink, Lara A1 - Alves, Sara G. A1 - de Holanda Coelho, Gabriel Lins A1 - Stieger, Stefan A1 - Schei, Vidar A1 - Hanel, Paul H. P. A1 - Szaszi, Barnabas A1 - Fedotov, Maksim A1 - Antfolk, Jan A1 - Marcu, Gabriela-Mariana A1 - Schrötter, Jana A1 - Kunst, Jonas R. A1 - Geiger, Sandra J. A1 - Adetula, Adeyemi A1 - Kocalar, Halil Emre A1 - Kielińska, Julita A1 - Kačmár, Pavol A1 - Bokkour, Ahmed A1 - Galindo-Caballero, Oscar J. A1 - Djamai, Ikhlas A1 - Pöntinen, Sara Johanna A1 - AGESIN, Bamikole Emmanuel A1 - Jernsäther, Teodor A1 - Urooj, Anum A1 - Rachev, Nikolay R. A1 - Koptjevskaja-Tamm, Maria A1 - Kurfalı, Murathan A1 - Pit, Ilse L. A1 - Li, Ranran A1 - Çoksan, Sami A1 - Dubrov, Dmitrii A1 - Paltrow, Tamar Elise A1 - Baník, Gabriel A1 - Korobova, Tatiana A1 - Studzinska, Anna A1 - Jiang, Xiaoming A1 - Aruta, John Jamir Benzon R. A1 - Vintr, Jáchym A1 - Chiu, Faith A1 - Kaliska, Lada A1 - Berkessel, Jana B. A1 - Tümer, Murat A1 - Morales-Izquierdo, Sara A1 - Chuan-Peng, Hu A1 - Vezirian, Kevin A1 - Rosa, Anna Dalla A1 - Bialobrzeska, Olga A1 - Vasilev, Martin R. A1 - Beitner, Julia A1 - Kácha, Ondřej A1 - Žuro, Barbara A1 - Westerlund, Minja A1 - Nedelcheva-Datsova, Mina A1 - Findor, Andrej A1 - Krupić, Dajana A1 - Kowal, Marta A1 - Askelund, Adrian Dahl A1 - Pourafshari, Razieh A1 - Đorđević, Jasna Milošević A1 - Schmidt, Nadya-Daniela A1 - Baklanova, Ekaterina A1 - Szala, Anna A1 - Zakharov, Ilya A1 - Vranka, Marek A. A1 - Ihaya, Keiko A1 - Grano, Caterina A1 - Cellini, Nicola A1 - Białek, Michał A1 - Anton-Boicuk, Lisa A1 - Dalgar, Ilker A1 - Adıgüzel, Arca A1 - Verharen, Jeroen P. H. A1 - Maturan, Princess Lovella G. A1 - Kassianos, Angelos P. A1 - Oliveira, Raquel A1 - Čadek, Martin A1 - Adoric, Vera Cubela A1 - Özdoğru, Asil Ali A1 - Sverdrup, Therese E. A1 - Aczel, Balazs A1 - Zambrano, Danilo A1 - Ahmed, Afroja A1 - Tamnes, Christian K. A1 - Yamada, Yuki A1 - Volz, Leonhard A1 - Sunami, Naoyuki A1 - Suter, Lilian A1 - Vieira, Luc A1 - Groyecka-Bernard, Agata A1 - Kamburidis, Julia Arhondis A1 - Reips, Ulf-Dietrich A1 - Harutyunyan, Mikayel A1 - Adetula, Gabriel Agboola A1 - Allred, Tara Bulut A1 - Barzykowski, Krystian A1 - Antazo, Benedict G A1 - Zsido, Andras N. A1 - Šakan, Dušana Dušan A1 - Cyrus-Lai, Wilson A1 - Ahlgren, Lina Pernilla A1 - Hruška, Matej A1 - Vega, Diego A1 - Manunta, Efisio A1 - Mokady, Aviv A1 - Capizzi, Mariagrazia A1 - Martončik, Marcel A1 - Say, Nicolas A1 - Filip, Katarzyna A1 - Vilar, Roosevelt A1 - Staniaszek, Karolina A1 - Vdovic, Milica A1 - Adamkovic, Matus A1 - Johannes, Niklas A1 - Hajdu, Nandor A1 - Cohen, Noga A1 - Overkott, Clara A1 - Krupić, Dino A1 - Hubena, Barbora A1 - Nilsonne, Gustav A1 - Mioni, Giovanna A1 - Solorzano, Claudio Singh A1 - Ishii, Tatsunori A1 - Chen, Zhang A1 - Kushnir, Elizaveta A1 - Karaarslan, Cemre A1 - Ribeiro, Rafael R. A1 - Khaoudi, Ahmed A1 - Kossowska, Małgorzata A1 - Bavolar, Jozef A1 - Hoyer, Karlijn A1 - Roczniewska, Marta A1 - Karababa, Alper A1 - Becker, Maja A1 - Monteiro, Renan P. A1 - Kunisato, Yoshihiko A1 - Metin-Orta, Irem A1 - Adamus, Sylwia A1 - Kozma, Luca A1 - Czarnek, Gabriela A1 - Domurat, Artur A1 - Štrukelj, Eva A1 - Alvarez, Daniela Serrato A1 - Parzuchowski, Michal A1 - Massoni, Sébastien A1 - Czamanski-Cohen, Johanna A1 - Pronizius, Ekaterina A1 - Muchembled, Fany A1 - van Schie, Kevin A1 - Saçaklı, Aslı A1 - Hristova, Evgeniya A1 - Kuzminska, Anna O. A1 - Charyate, Abdelilah A1 - Bijlstra, Gijsbert A1 - Afhami, Reza A1 - Majeed, Nadyanna M. A1 - Musser, Erica D. A1 - Sirota, Miroslav A1 - Ross, Robert M. A1 - Yeung, Siu Kit A1 - Papadatou-Pastou, Marietta A1 - Foroni, Francesco A1 - Almeida, Inês A. T. A1 - Grigoryev, Dmitry A1 - Lewis, David M. G. A1 - Holford, Dawn L. A1 - Janssen, Steve M. J. A1 - Tatachari, Srinivasan A1 - Batres, Carlota A1 - Olofsson, Jonas K. A1 - Daches, Shimrit A1 - Belaus, Anabel A1 - Pfuhl, Gerit A1 - Corral-Frias, Nadia Sarai A1 - Sousa, Daniela A1 - Röer, Jan Philipp A1 - Isager, Peder Mortvedt A1 - Godbersen, Hendrik A1 - Walczak, Radoslaw B. A1 - Van Doren, Natalia A1 - Ren, Dongning A1 - Gill, Tripat A1 - Voracek, Martin A1 - DeBruine, Lisa M. A1 - Anne, Michele A1 - Očovaj, Sanja Batić A1 - Thomas, Andrew G. A1 - Arvanitis, Alexios A1 - Ostermann, Thomas A1 - Wolfe, Kelly A1 - Arinze, Nwadiogo Chisom A1 - Bundt, Carsten A1 - Lamm, Claus A1 - Calin-Jageman, Robert J A1 - Davis, William E. A1 - Karekla, Maria A1 - Zorjan, Saša A1 - Jaremka, Lisa M. A1 - Uttley, Jim A1 - Hricova, Monika A1 - Koehn, Monica A A1 - Kiselnikova, Natalia A1 - Bai, Hui A1 - Krafnick, Anthony J. A1 - Balci, Busra Bahar A1 - Ballantyne, Tonia A1 - Lins, Samuel A1 - Vally, Zahir A1 - Esteban-Serna, Celia A1 - Schmidt, Kathleen A1 - Macapagal, Paulo Manuel L. A1 - Szwed, Paulina A1 - Zdybek, Przemysław Marcin A1 - Moreau, David A1 - Collins, W. Matthew A1 - Joy-Gaba, Jennifer A. A1 - Vilares, Iris A1 - Tran, Ulrich S. A1 - Boudesseul, Jordane A1 - Albayrak-Aydemir, Nihan A1 - Dixson, Barnaby James Wyld A1 - Perillo, Jennifer T A1 - Ferreira, Ana A1 - Westgate, Erin C. A1 - Aberson, Christopher L. A1 - Arinze, Azuka Ikechukwu A1 - Jaeger, Bastian A1 - Butt, Muhammad Mussaffa A1 - Silva, Jaime R. A1 - Storage, Daniel Shafik A1 - Janak, Allison P A1 - Jiménez-Leal, William A1 - Soto, Jose A. A1 - Sorokowska, Agnieszka A1 - McCarthy, Randy A1 - Tullett, Alexa M A1 - Frias-Armenta, Martha A1 - Ribeiro, Matheus Fernando Felix A1 - Hartanto, Andree A1 - Forbes, Paul A. G. A1 - Willis, Megan L. A1 - del Carmen Tejada R, María A1 - Torres, Adriana Julieth Olaya A1 - Stephen, Ian D A1 - Vaidis, David C. A1 - de la Rosa-Gómez, Anabel A1 - Yu, Karen A1 - Sutherland, Clare A. M. A1 - Manavalan, Mathi A1 - Behzadnia, Behzad A1 - Urban, Jan A1 - Baskin, Ernest A1 - McFall, Joseph P. A1 - Ogbonnaya, Chisom Esther A1 - Fu, Cynthia H. Y. A1 - Rahal, Rima-Maria A1 - Ndukaihe, Izuchukwu L. G. A1 - Hostler, Thomas J. A1 - Kappes, Heather Barry A1 - Sorokowski, Piotr A1 - Khosla, Meetu A1 - Lazarevic, Ljiljana B. A1 - Eudave, Luis A1 - Vilsmeier, Johannes K. A1 - Luis, Elkin O. A1 - Muda, Rafał A1 - Agadullina, Elena A1 - Cárcamo, Rodrigo A. A1 - Reeck, Crystal A1 - Anjum, Gulnaz A1 - Venegas, Mónica Camila Toro A1 - Misiak, Michal A1 - Ryan, Richard M. A1 - Nock, Nora L. A1 - Travaglino, Giovanni A. A1 - Mensink, Michael C. A1 - Feldman, Gilad A1 - Wichman, Aaron L. A1 - Chou, Weilun A1 - Ziano, Ignazio A1 - Seehuus, Martin A1 - Chopik, William J. A1 - Kung, Franki Y. H. A1 - Carpentier, Joelle A1 - Vaughn, Leigh Ann A1 - Du, Hongfei A1 - Xiao, Qinyu A1 - Lima, Tiago J. S. A1 - Noone, Chris A1 - Onie, Sandersan A1 - Verbruggen, Frederick A1 - Radtke, Theda A1 - Primbs, Maximilian A. T1 - The psychological science accelerator’s COVID-19 rapid-response dataset T2 - Scientific Data Y1 - 2023 U6 - https://doi.org/10.1038/s41597-022-01811-7 SN - 2052-4463 VL - 10 IS - 1 SP - 1 EP - 15 PB - Springer Science and Business Media LLC ER -