TY - THES A1 - Herzog, Michael T1 - Instrumente zur Potentialabschätzung und Einführung von Telekooperation in kleinen und mittleren Unternehmen - Organisationgestaltung, Technik und Wirtschaftlichkeit Y1 - 2001 ER - 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 - Kay, Sonja A1 - Rega, Carlo A1 - Moreno, Gerardo A1 - Herder, Michael den A1 - Palma, João H. N. A1 - Borek, Robert A1 - Crous-Duran, Josep A1 - Freese, Dirk A1 - Giannitsopoulos, Michail A1 - Graves, Anil A1 - Jäger, Mareike A1 - Lamersdorf, Norbert A1 - Memedemin, Daniyar A1 - Mosquera-Losada, R. A1 - Pantera, Anastasia A1 - Paracchini, Maria Luisa A1 - Paris, Pierluigi A1 - Roces-Díaz, José V. A1 - Rolo, Victor A1 - Rosati, Adolfo A1 - Sandor, Mignon A1 - Smith, Jo A1 - Szerencsits, Erich A1 - Varga, Anna A1 - Viaud, Valérie A1 - Wawer, Rafal A1 - Burgess, Paul J. A1 - Herzog, Felix T1 - Agroforestry creates carbon sinks whilst enhancing the environment in agricultural landscapes in Europe T2 - Land Use Policy N2 - Agroforestry, relative to conventional agriculture, contributes significantly to carbon sequestration, increases a range of regulating ecosystem services, and enhances biodiversity. Using a transdisciplinary approach, we combined scientific and technical knowledge to evaluate nine environmental pressures in terms of ecosystem services in European farmland and assessed the carbon storage potential of suitable agroforestry systems, proposed by regional experts. First, regions with potential environmental pressures were identified with respect to soil health (soil erosion by water and wind, low soil organic carbon), water quality (water pollution by nitrates, salinization by irrigation), areas affected by climate change (rising temperature), and by underprovision in biodiversity (pollination and pest control pressures, loss of soil biodiversity). The maps were overlaid to identify areas where several pressures accumulate. In total, 94.4% of farmlands suffer from at least one environmental pressure, pastures being less affected than arable lands. Regional hotspots were located in north-western France, Denmark, Central Spain, north and south-western Italy, Greece, and eastern Romania. The 10% of the area with the highest number of accumulated pressures were defined as Priority Areas, where the implementation of agroforestry could be particularly effective. In a second step, European agroforestry experts were asked to propose agroforestry practices suitable for the Priority Areas they were familiar with, and identified 64 different systems covering a wide range of practices. These ranged from hedgerows on field boundaries to fast growing coppices or scattered single tree systems. Third, for each proposed system, the carbon storage potential was assessed based on data from the literature and the results were scaled-up to the Priority Areas. As expected, given the wide range of agroforestry practices identified, the carbon sequestration potentials ranged between 0.09 and 7.29 t C ha −1 a −1 . Implementing agroforestry on the Priority Areas could lead to a sequestration of 2.1 to 63.9 million t C a −1 (7.78 and 234.85 million t CO 2eq a −1 ) depending on the type of agroforestry. This corresponds to between 1.4 and 43.4% of European agricultural greenhouse gas (GHG) emissions. Moreover, promoting agroforestry in the Priority Areas would contribute to mitigate the environmental pressures identified there. We conclude that the strategic and spatially targeted establishment of agroforestry systems could provide an effective means of meeting EU policy objectives on GHG emissions whilst providing a range of other important benefits. Y1 - 2019 U6 - https://doi.org/10.1016/j.landusepol.2019.02.025 SN - 0264-8377 VL - 83 SP - 581 EP - 593 ER -