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 - RPRT A1 - Müller, Jörg A1 - Dieter, M. A1 - Bauhus, J. A1 - Spellmann, H. A1 - Möhring, B. A1 - Wagner, S. A1 - Wolf, Heino A1 - Niekisch, M. A1 - Weiger, H. A1 - Feindt, Peter H. A1 - Hamm, Ulrich A1 - Wätzold, Frank A1 - Wolters, Volkmar A1 - Engels, Eve-Marie A1 - Schraml, U. A1 - Lang, F. A1 - Pröbstl-Haider, U. A1 - Richter, K. T1 - Wege zu einem effizienten Waldnaturschutz in Deutschland. Stellungnahme Y1 - 2020 UR - http://www.fnr.de/fileadmin/allgemein/pdf/Effizienter_Waldnaturschutz_in_Deutschland.pdf PB - Wissenschaftlicher Beirat Waldpolitik und Wissenschaftlicher Beirat Biodiversität und Genetische Ressourcen beim BMEL ER - TY - CHAP A1 - Henkel, Karsten A1 - Schwiertz, Carola A1 - Wagner, S. A1 - Valdeig, A. A1 - List, M. A1 - Schmeißer, Dieter T1 - Partikel- und Tropfendetektion im Mikrometerbereich mittels Schwingquarzen Y1 - 2003 SN - 3-935712-92-8 SP - 291 EP - 294 PB - w.e.b.-Univ.-Verl. CY - Dresden ER - TY - GEN A1 - Steuer, O. A1 - Liedke, Maciej O. A1 - Butterling, M. A1 - Schwarz, D. A1 - Schulze, J. A1 - Li, Z. A1 - Wagner, A. A1 - Fischer, Inga Anita A1 - Hübner, R. A1 - Zhou, S. T1 - Evolution of point defects in pulsed-laser-melted Ge1-xSnx probed by positron annihilation lifetime spectroscopy T2 - Journal of Physics: Condensed Matter N2 - Direct-band-gap Germanium-Tin alloys (Ge1-xSnx) with high carrier mobilities are promising materials for nano- and optoelectronics. The concentration of open volume defects in the alloy, such as Sn and Ge vacancies, influences the final device performance. In this article, we present an evaluation of the point defects in molecular-beam-epitaxy grown Ge1-xSnx films treated by post-growth nanosecond-range pulsed laser melting (PLM). Doppler broadening – variable energy positron annihilation spectroscopy and variable energy positron annihilation lifetime spectroscopy are used to investigate the defect nanostructure in the Ge1-xSnx films exposed to increasing laser energy density. The experimental results, supported with ATomic SUPerposition calculations, evidence that after PLM, the average size of the open volume defects increases, which represents a raise in concentration of vacancy agglomerations, but the overall defect density is reduced as a function of the PLM fluence. At the same time, the positron annihilation spectroscopy analysis provides information about dislocations and Ge vacancies decorated by Sn atoms. Moreover, it is shown that the PLM reduces the strain in the layer, while dislocations are responsible for trapping of Sn and formation of small Sn-rich-clusters. KW - GeSn KW - laser annealing KW - positron annihilation KW - PLM KW - point defects Y1 - 2023 UR - https://iopscience.iop.org/article/10.1088/1361-648X/ad0a10/meta U6 - https://doi.org/10.1088/1361-648X/ad0a10 SN - 0953-8984 VL - 36 IS - 8 SP - 1 EP - 11 ER - TY - CHAP A1 - Wagner, J. A1 - Ostendorf, Ralf A1 - Grahmann, Jan A1 - Merten, A. A1 - Hugger, S. A1 - Jarvis, J.-P. A1 - Fuchs, F. A1 - Boscovic, D. A1 - Schenk, Harald ED - Razeghi, Manijeh T1 - Widely tunable quantum cascade lasers for spectroscopic sensing T2 - Quantum sensing and nanophotonic devices XII, 8 - 12 February 2015, San Francisco, California, United States Y1 - 2015 SN - 978-1-62841-460-8 SP - 937012-1 EP - 937012-6 PB - SPIE CY - Bellingham, Wash. ER - TY - CHAP A1 - Rodionov, Andrei A1 - Bens, Oliver A1 - Trimborn, Manfred A1 - Wagner, S. A1 - Schneider, Bernd Uwe A1 - Raab, Thomas A1 - Hüttl, Reinhard F. T1 - Use of commercial soil amendments in initial soils (I) - Impact on yield and basic soil characteristics T2 - EGU General Assembly 2009, Vienna, Austria, 19 – 24 April 2009 Y1 - 2009 N1 - EGU2009-12080 PB - European Geophysical Society CY - Katlenburg-Lindau ER -