TY - JOUR A1 - Fischer, Matthias A1 - Raabe, Thomas T1 - Animal models for Coffin-Lowry syndrome: RSK2 and nervous system dysfunction JF - Frontiers in Behavioral Neuroscience N2 - Loss of function mutations in the rsk2 gene cause Coffin-Lowry syndrome (CLS), which is associated with multiple symptoms including severe mental disabilities. Despite the characterization of ribosomal S6 kinase 2 (RSK2) as a protein kinase acting as a downstream effector of the well characterized ERK MAP-kinase signaling pathway, it turns out to be a challenging task to link RSK2 to specific neuronal processes dysregulated in case of mutation. Animal models such as mouse and Drosophila combine advanced genetic manipulation tools with in vivo imaging techniques, high-resolution connectome analysis and a variety of behavioral assays, thereby allowing for an in-depth analysis for gene functions in the nervous system. Although modeling mental disability in animal systems has limitations because of the complexity of phenotypes, the influence of genetic variation and species-specific characteristics at the neural circuit and behavioral level, some common aspects of RSK2 function in the nervous system have emerged, which will be presented. Only with this knowledge our understanding of the pathophysiology of CLS can be improved, which might open the door for development of potential intervention strategies. KW - Coffin-Lowry syndrome KW - RSK2 KW - mental disorders KW - mouse model KW - Drosophila model KW - neuronal dysfunction KW - behavior Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-176799 VL - 12 IS - 106 ER - TY - JOUR A1 - Fischer, Matthias A1 - Heinrichs, Harald T1 - Dimensions, dialectic, discourse. Three political perspectives on the sustainability of the German healthcare system JF - International Journal of Environmental Research and Public Health N2 - This review article deals with the topic of sustainability in the German healthcare system and presents an overview of how the six articles of our research relate to one another. After introducing to the context of the research, its internal principles, and the methods applied, three perspectives are presented, each also discussed in terms of the respective literature in sustainability science and political science. The review concludes by presenting a circular model and by discussing the general limitations as well as the practical implications of our research. KW - sustainability KW - German healthcare system KW - policy KW - politics KW - polity Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-177003 VL - 15 IS - 7 ER - TY - JOUR A1 - Ziegler, Alice A1 - Meyer, Hanna A1 - Otte, Insa A1 - Peters, Marcell K. A1 - Appelhans, Tim A1 - Behler, Christina A1 - Böhning-Gaese, Katrin A1 - Classen, Alice A1 - Detsch, Florian A1 - Deckert, Jürgen A1 - Eardley, Connal D. A1 - Ferger, Stefan W. A1 - Fischer, Markus A1 - Gebert, Friederike A1 - Haas, Michael A1 - Helbig-Bonitz, Maria A1 - Hemp, Andreas A1 - Hemp, Claudia A1 - Kakengi, Victor A1 - Mayr, Antonia V. A1 - Ngereza, Christine A1 - Reudenbach, Christoph A1 - Röder, Juliane A1 - Rutten, Gemma A1 - Schellenberger Costa, David A1 - Schleuning, Matthias A1 - Ssymank, Axel A1 - Steffan-Dewenter, Ingolf A1 - Tardanico, Joseph A1 - Tschapka, Marco A1 - Vollstädt, Maximilian G. R. A1 - Wöllauer, Stephan A1 - Zhang, Jie A1 - Brandl, Roland A1 - Nauss, Thomas T1 - Potential of airborne LiDAR derived vegetation structure for the prediction of animal species richness at Mount Kilimanjaro JF - Remote Sensing N2 - The monitoring of species and functional diversity is of increasing relevance for the development of strategies for the conservation and management of biodiversity. Therefore, reliable estimates of the performance of monitoring techniques across taxa become important. Using a unique dataset, this study investigates the potential of airborne LiDAR-derived variables characterizing vegetation structure as predictors for animal species richness at the southern slopes of Mount Kilimanjaro. To disentangle the structural LiDAR information from co-factors related to elevational vegetation zones, LiDAR-based models were compared to the predictive power of elevation models. 17 taxa and 4 feeding guilds were modeled and the standardized study design allowed for a comparison across the assemblages. Results show that most taxa (14) and feeding guilds (3) can be predicted best by elevation with normalized RMSE values but only for three of those taxa and two of those feeding guilds the difference to other models is significant. Generally, modeling performances between different models vary only slightly for each assemblage. For the remaining, structural information at most showed little additional contribution to the performance. In summary, LiDAR observations can be used for animal species prediction. However, the effort and cost of aerial surveys are not always in proportion with the prediction quality, especially when the species distribution follows zonal patterns, and elevation information yields similar results. KW - biodiversity KW - species richness KW - LiDAR KW - elevation KW - partial least square regression KW - arthropods KW - birds KW - bats KW - predictive modeling Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-262251 SN - 2072-4292 VL - 14 IS - 3 ER - TY - JOUR A1 - Gunesch, Sandra A1 - Hoffmann, Matthias A1 - Kiermeier, Carolina A1 - Fischer, Wolfgang A1 - Pinto, Antonio F. M. A1 - Maurice, Tangui A1 - Maher, Pamela A1 - Decker, Michael T1 - 7-O-Esters of taxifolin with pronounced and overadditive effects in neuroprotection, anti-neuroinflammation, and amelioration of short-term memory impairment in vivo JF - Redox Biology N2 - Alzheimer's disease (AD) is a multifactorial disease and the most common form of dementia. There are no treatments to cure, prevent or slow down the progression of the disease. Natural products hold considerable interest for the development of preventive neuroprotectants to treat neurodegenerative disorders like AD, due to their low toxicity and general beneficial effects on human health with their anti-inflammatory and antioxidant features. In this work we describe regioselective synthesis of 7-O-ester hybrids of the flavonoid taxifolin with the phenolic acids cinnamic and ferulic acid, namely 7-O-cinnamoyltaxifolin and 7-O-feruloyltaxifolin. The compounds show pronounced overadditive neuroprotective effects against oxytosis, ferroptosis and ATP depletion in the murine hippocampal neuron HT22 cell model. Furthermore, 7-O-cinnamoyltaxifolin and 7-O-feruloyltaxifolin reduced LPS-induced neuroinflammation in BV-2 microglia cells as assessed by effects on the levels of NO, IL6 and TNFα. In all in vitro assays the 7-O-esters of taxifolin and ferulic or cinnamic acid showed strong overadditive activity, significantly exceeding the effects of the individual components and the equimolar mixtures thereof, which were almost inactive in all of the assays at the tested concentrations. In vivo studies confirmed this overadditive effect. Treatment of an AD mouse model based on the injection of oligomerized Aβ\(_{25-35}\) peptide into the brain to cause neurotoxicity and subsequently memory deficits with 7-O-cinnamoyltaxifolin or 7-O-feruloyltaxifolin resulted in improved performance in an assay for short-term memory as compared to vehicle and mice treated with the respective equimolar mixtures. These results highlight the benefits of natural product hybrids as a novel compound class with potential use for drug discovery in neurodegenerative diseases due to their pharmacological profile that is distinct from the individual natural components. KW - Alzheimer's disease KW - Natural product hybrids KW - Flavonoids KW - Phenolic acids KW - Microglia KW - In vivo studies Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-202718 VL - 29 ER - TY - JOUR A1 - Salehi, Saeede A1 - Zare, Abdolhossein A1 - Prezza, Gianluca A1 - Bader, Jakob A1 - Schneider, Cornelius A1 - Fischer, Utz A1 - Meissner, Felix A1 - Mann, Matthias A1 - Briese, Michael A1 - Sendtner, Michael T1 - Cytosolic Ptbp2 modulates axon growth in motoneurons through axonal localization and translation of Hnrnpr JF - Nature Communications N2 - The neuronal RNA-binding protein Ptbp2 regulates neuronal differentiation by modulating alternative splicing programs in the nucleus. Such programs contribute to axonogenesis by adjusting the levels of protein isoforms involved in axon growth and branching. While its functions in alternative splicing have been described in detail, cytosolic roles of Ptbp2 for axon growth have remained elusive. Here, we show that Ptbp2 is located in the cytosol including axons and growth cones of motoneurons, and that depletion of cytosolic Ptbp2 affects axon growth. We identify Ptbp2 as a major interactor of the 3’ UTR of Hnrnpr mRNA encoding the RNA-binding protein hnRNP R. Axonal localization of Hnrnpr mRNA and local synthesis of hnRNP R protein are strongly reduced when Ptbp2 is depleted, leading to defective axon growth. Ptbp2 regulates hnRNP R translation by mediating the association of Hnrnpr with ribosomes in a manner dependent on the translation factor eIF5A2. Our data thus suggest a mechanism whereby cytosolic Ptbp2 modulates axon growth by fine-tuning the mRNA transport and local synthesis of an RNA-binding protein. KW - molecular neuroscience KW - RNA-binding proteins KW - RNA transport Y1 - 2023 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-357639 VL - 14 ER - TY - JOUR A1 - Albrecht, Jörg A1 - Classen, Alice A1 - Vollstädt, Maximilian G.R. A1 - Mayr, Antonia A1 - Mollel, Neduvoto P. A1 - Schellenberger Costa, David A1 - Dulle, Hamadi I. A1 - Fischer, Markus A1 - Hemp, Andreas A1 - Howell, Kim M. A1 - Kleyer, Michael A1 - Nauss, Thomas A1 - Peters, Marcell K. A1 - Tschapka, Marco A1 - Steffan-Dewenter, Ingolf A1 - Böhning-Gaese, Katrin A1 - Schleuning, Matthias T1 - Plant and animal functional diversity drive mutualistic network assembly across an elevational gradient JF - Nature Communications N2 - Species' functional traits set the blueprint for pair-wise interactions in ecological networks. Yet, it is unknown to what extent the functional diversity of plant and animal communities controls network assembly along environmental gradients in real-world ecosystems. Here we address this question with a unique dataset of mutualistic bird-fruit, bird-flower and insect-flower interaction networks and associated functional traits of 200 plant and 282 animal species sampled along broad climate and land-use gradients on Mt. Kilimanjaro. We show that plant functional diversity is mainly limited by precipitation, while animal functional diversity is primarily limited by temperature. Furthermore, shifts in plant and animal functional diversity along the elevational gradient control the niche breadth and partitioning of the respective other trophic level. These findings reveal that climatic constraints on the functional diversity of either plants or animals determine the relative importance of bottom-up and top-down control in plant-animal interaction networks. KW - Traits-Environment Relationships KW - Species Traits KW - Ecological Networks KW - 4TH-Corner Problem KW - Multiple Traits KW - Bottom-up KW - Biodiversity KW - Community ecology KW - Ecological networks KW - Ecology KW - Ecosystem ecology Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-221056 VL - 9 ER -