@phdthesis{Herzog, author = {Herzog, Michael}, title = {Instrumente zur Potentialabsch{\"a}tzung und Einf{\"u}hrung von Telekooperation in kleinen und mittleren Unternehmen - Organisationgestaltung, Technik und Wirtschaftlichkeit}, language = {de} } @misc{KuenzelHoffmannWeberetal., author = {K{\"u}nzel, Stephan R. and Hoffmann, Maximilian and Weber, Silvio and K{\"u}nzel, Karolina and K{\"a}mmerer, Susanne and G{\"u}nscht, Mario and Klapproth, Erik and Rausch, Johanna S. E. and Sadek, Mirna S. and Kolanowski, Tomasz and Meyer-Roxlau, Stefanie and Piorkowski, Christopher and Tugtekin, Sems M. and Rose-John, Stefan and Yin, Xiaoke and Mayr, Manuel and Kuhlmann, Jan Dominik and Wimberger, Pauline and Gr{\"u}tzmann, Konrad and Herzog, Natalie and K{\"u}pper, Jan-Heiner and O'Reilly, Molly and Kabir, S. Nashitha and Sommerfeld, Laura C. and Guan, Kaomei and Wielockx, Ben and Fabritz, Larissa and Nattel, Stanley and Ravens, Ursula and Dobrev, Dobromir and Wagner, Michael and El-Armouche, Ali}, title = {Diminished PLK2 Induces Cardiac Fibrosis and Promotes Atrial Fibrillation}, series = {Circulation Research}, volume = {129}, journal = {Circulation Research}, number = {8}, issn = {1524-4571}, doi = {10.1161/CIRCRESAHA.121.319425}, pages = {804 -- 820}, abstract = {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.}, language = {en} } @misc{KayRegaMorenoetal., author = {Kay, Sonja and Rega, Carlo and Moreno, Gerardo and Herder, Michael den and Palma, Jo{\~a}o H. N. and Borek, Robert and Crous-Duran, Josep and Freese, Dirk and Giannitsopoulos, Michail and Graves, Anil and J{\"a}ger, Mareike and Lamersdorf, Norbert and Memedemin, Daniyar and Mosquera-Losada, R. and Pantera, Anastasia and Paracchini, Maria Luisa and Paris, Pierluigi and Roces-D{\´i}az, Jos{\´e} V. and Rolo, Victor and Rosati, Adolfo and Sandor, Mignon and Smith, Jo and Szerencsits, Erich and Varga, Anna and Viaud, Val{\´e}rie and Wawer, Rafal and Burgess, Paul J. and Herzog, Felix}, title = {Agroforestry creates carbon sinks whilst enhancing the environment in agricultural landscapes in Europe}, series = {Land Use Policy}, volume = {83}, journal = {Land Use Policy}, issn = {0264-8377}, doi = {10.1016/j.landusepol.2019.02.025}, pages = {581 -- 593}, abstract = {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.}, language = {en} }