@article{HaakeHaackSchaeferetal.2023, author = {Haake, Markus and Haack, Beatrice and Sch{\"a}fer, Tina and Harter, Patrick N. and Mattavelli, Greta and Eiring, Patrick and Vashist, Neha and Wedekink, Florian and Genssler, Sabrina and Fischer, Birgitt and Dahlhoff, Julia and Mokhtari, Fatemeh and Kuzkina, Anastasia and Welters, Marij J. P. and Benz, Tamara M. and Sorger, Lena and Thiemann, Vincent and Almanzar, Giovanni and Selle, Martina and Thein, Klara and Sp{\"a}th, Jacob and Gonzalez, Maria Cecilia and Reitinger, Carmen and Ipsen-Escobedo, Andrea and Wistuba-Hamprecht, Kilian and Eichler, Kristin and Filipski, Katharina and Zeiner, Pia S. and Beschorner, Rudi and Goedemans, Renske and Gogolla, Falk Hagen and Hackl, Hubert and Rooswinkel, Rogier W. and Thiem, Alexander and Romer Roche, Paula and Joshi, Hemant and P{\"u}hringer, Dirk and W{\"o}ckel, Achim and Diessner, Joachim E. and R{\"u}diger, Manfred and Leo, Eugen and Cheng, Phil F. and Levesque, Mitchell P. and Goebeler, Matthias and Sauer, Markus and Nimmerjahn, Falk and Schuberth-Wagner, Christine and Felten, Stefanie von and Mittelbronn, Michel and Mehling, Matthias and Beilhack, Andreas and van der Burg, Sjoerd H. and Riedel, Angela and Weide, Benjamin and Dummer, Reinhard and Wischhusen, J{\"o}rg}, title = {Tumor-derived GDF-15 blocks LFA-1 dependent T cell recruitment and suppresses responses to anti-PD-1 treatment}, series = {Nature Communications}, volume = {14}, journal = {Nature Communications}, doi = {10.1038/s41467-023-39817-3}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-357333}, year = {2023}, abstract = {Immune checkpoint blockade therapy is beneficial and even curative for some cancer patients. However, the majority don't respond to immune therapy. Across different tumor types, pre-existing T cell infiltrates predict response to checkpoint-based immunotherapy. Based on in vitro pharmacological studies, mouse models and analyses of human melanoma patients, we show that the cytokine GDF-15 impairs LFA-1/β2-integrin-mediated adhesion of T cells to activated endothelial cells, which is a pre-requisite of T cell extravasation. In melanoma patients, GDF-15 serum levels strongly correlate with failure of PD-1-based immune checkpoint blockade therapy. Neutralization of GDF-15 improves both T cell trafficking and therapy efficiency in murine tumor models. Thus GDF-15, beside its known role in cancer-related anorexia and cachexia, emerges as a regulator of T cell extravasation into the tumor microenvironment, which provides an even stronger rationale for therapeutic anti-GDF-15 antibody development.}, language = {en} } @article{SchleuningFarwigPetersetal.2011, author = {Schleuning, Matthias and Farwig, Nina and Peters, Marcell K. and Bergsdorf, Thomas and Bleher, B{\"a}rbel and Brandl, Roland and Dalitz, Helmut and Fischer, Georg and Freund, Wolfram and Gikungu, Mary W. and Hagen, Melanie and Garcia, Francisco Hita and Kagezi, Godfrey H. and Kaib, Manfred and Kraemer, Manfred and Lung, Tobias and Naumann, Clas M. and Schaab, Gertrud and Templin, Mathias and Uster, Dana and W{\"a}gele, J. Wolfgang and B{\"o}hning-Gaese, Katrin}, title = {Forest Fragmentation and Selective Logging Have Inconsistent Effects on Multiple Animal-Mediated Ecosystem Processes in a Tropical Forest}, series = {PLoS ONE}, volume = {6}, journal = {PLoS ONE}, number = {11}, doi = {10.1371/journal.pone.0027785}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-140093}, pages = {e27785}, year = {2011}, abstract = {Forest fragmentation and selective logging are two main drivers of global environmental change and modify biodiversity and environmental conditions in many tropical forests. The consequences of these changes for the functioning of tropical forest ecosystems have rarely been explored in a comprehensive approach. In a Kenyan rainforest, we studied six animal-mediated ecosystem processes and recorded species richness and community composition of all animal taxa involved in these processes. We used linear models and a formal meta-analysis to test whether forest fragmentation and selective logging affected ecosystem processes and biodiversity and used structural equation models to disentangle direct from biodiversity-related indirect effects of human disturbance on multiple ecosystem processes. Fragmentation increased decomposition and reduced antbird predation, while selective logging consistently increased pollination, seed dispersal and army-ant raiding. Fragmentation modified species richness or community composition of five taxa, whereas selective logging did not affect any component of biodiversity. Changes in the abundance of functionally important species were related to lower predation by antbirds and higher decomposition rates in small forest fragments. The positive effects of selective logging on bee pollination, bird seed dispersal and army-ant raiding were direct, i.e. not related to changes in biodiversity, and were probably due to behavioural changes of these highly mobile animal taxa. We conclude that animal-mediated ecosystem processes respond in distinct ways to different types of human disturbance in Kakamega Forest. Our findings suggest that forest fragmentation affects ecosystem processes indirectly by changes in biodiversity, whereas selective logging influences processes directly by modifying local environmental conditions and resource distributions. The positive to neutral effects of selective logging on ecosystem processes show that the functionality of tropical forests can be maintained in moderately disturbed forest fragments. Conservation concepts for tropical forests should thus include not only remaining pristine forests but also functionally viable forest remnants.}, language = {en} } @article{RamlerPoaterHirschetal.2019, author = {Ramler, Jacqueline and Poater, Jordi and Hirsch, Florian and Ritschel, Benedikt and Fischer, Ingo and Bickelhaupt, F. Matthias and Lichtenberg, Crispin}, title = {Carbon monoxide insertion at a heavy p-block element: unprecedented formation of a cationic bismuth carbamoyl}, series = {Chemical Science}, volume = {10}, journal = {Chemical Science}, doi = {10.1039/C9SC00278B}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-181627}, pages = {4169 - 4176}, year = {2019}, abstract = {Major advances in the chemistry of 5th and 6th row heavy p-block element compounds have recently uncovered intriguing reactivity patterns towards small molecules such as H\(_2\), CO\(_2\), and ethylene. However, well-defined, homogeneous insertion reactions with carbon monoxide, one of the benchmark substrates in this field, have not been reported to date. We demonstrate here, that a cationic bismuth amide undergoes facile insertion of CO into the Bi-N bond under mild conditions. This approach grants direct access to the first cationic bismuth carbamoyl species. Its characterization by NMR, IR, and UV/vis spectroscopy, elemental analysis, single-crystal X-ray analysis, cyclic voltammetry, and DFT calculations revealed intriguing properties, such as a reversible electron transfer at the bismuth center and an absorption feature at 353 nm ascribed to a transition involving σ- and π-type orbitals of the bismuth-carbamoyl functionality. A combined experimental and theoretical approach provided insight into the mechanism of CO insertion. The substrate scope could be extended to isonitriles.}, language = {en} } @article{BeckEhmannAndlaueretal.2015, author = {Beck, Katherina and Ehmann, Nadine and Andlauer, Till F. M. and Ljaschenko, Dmitrij and Strecker, Katrin and Fischer, Matthias and Kittel, Robert J. and Raabe, Thomas}, title = {Loss of the Coffin-Lowry syndrome-associated gene RSK2 alters ERK activity, synaptic function and axonal transport in Drosophila motoneurons}, series = {Disease Models \& Mechanisms}, volume = {8}, journal = {Disease Models \& Mechanisms}, doi = {10.1242/dmm.021246}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-145185}, pages = {1389-1400}, year = {2015}, abstract = {Plastic changes in synaptic properties are considered as fundamental for adaptive behaviors. Extracellular-signal-regulated kinase (ERK)-mediated signaling has been implicated in regulation of synaptic plasticity. Ribosomal S6 kinase 2 (RSK2) acts as a regulator and downstream effector of ERK. In the brain, RSK2 is predominantly expressed in regions required for learning and memory. Loss-of-function mutations in human RSK2 cause Coffin-Lowry syndrome, which is characterized by severe mental retardation and low IQ scores in affected males. Knockout of RSK2 in mice or the RSK ortholog in Drosophila results in a variety of learning and memory defects. However, overall brain structure in these animals is not affected, leaving open the question of the pathophysiological consequences. Using the fly neuromuscular system as a model for excitatory glutamatergic synapses, we show that removal of RSK function causes distinct defects in motoneurons and at the neuromuscular junction. Based on histochemical and electrophysiological analyses, we conclude that RSK is required for normal synaptic morphology and function. Furthermore, loss of RSK function interferes with ERK signaling at different levels. Elevated ERK activity was evident in the somata of motoneurons, whereas decreased ERK activity was observed in axons and the presynapse. In addition, we uncovered a novel function of RSK in anterograde axonal transport. Our results emphasize the importance of fine-tuning ERK activity in neuronal processes underlying higher brain functions. In this context, RSK acts as a modulator of ERK signaling.}, language = {en} } @article{AmthorWeissenseelFischeretal.2014, author = {Amthor, Matthias and Weißenseel, Sebastian and Fischer, Julian and Kamp, Martin and Schneider, Christian and H{\"o}fling, Sven}, title = {Electro-optical switching between polariton and cavity lasing in an InGaAs quantum well microcavity}, doi = {10.1364/OE.22.031146}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-111130}, year = {2014}, abstract = {We report on the condensation of microcavity exciton polaritons under optical excitation in a microcavity with four embedded InGaAs quantum wells. The polariton laser is characterized by a distinct nonlinearity in the input-output-characteristics, which is accompanied by a drop of the emission linewidth indicating temporal coherence and a characteristic persisting emission blueshift with increased particle density. The temporal coherence of the device at threshold is underlined by a characteristic drop of the second order coherence function to a value close to 1. Furthermore an external electric field is used to switch between polariton regime, polariton condensate and photon lasing.}, language = {en} } @article{NgwaScheuermayerMairetal.2013, author = {Ngwa, Che Julius and Scheuermayer, Matthias and Mair, Gunnar Rudolf and Kern, Selina and Br{\"u}gl, Thomas and Wirth, Christine Clara and Aminake, Makoah Nigel and Wiesner, Jochen and Fischer, Rainer and Vilcinskas, Andreas and Pradel, Gabriele}, title = {Changes in the transcriptome of the malaria parasite Plasmodium falciparum during the initial phase of transmission from the human to the mosquito}, series = {BMC Genomics}, volume = {14}, journal = {BMC Genomics}, number = {256}, issn = {1471-2164}, doi = {10.1186/1471-2164-14-256}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-121905}, year = {2013}, abstract = {Background: The transmission of the malaria parasite Plasmodium falciparum from the human to the mosquito is mediated by dormant sexual precursor cells, the gametocytes, which become activated in the mosquito midgut. Because gametocytes are the only parasite stages able to establish an infection in the mosquito, they play a crucial role in spreading the tropical disease. The human-to-mosquito transmission triggers important molecular changes in the gametocytes, which initiate gametogenesis and prepare the parasite for life-cycle progression in the insect vector. Results: To better understand gene regulations during the initial phase of malaria parasite transmission, we focused on the transcriptome changes that occur within the first half hour of parasite development in the mosquito. Comparison of mRNA levels of P. falciparum gametocytes before and 30 min following activation using suppression subtractive hybridization (SSH) identified 126 genes, which changed in expression during gametogenesis. Among these, 17.5\% had putative functions in signaling, 14.3\% were assigned to cell cycle and gene expression, 8.7\% were linked to the cytoskeleton or inner membrane complex, 7.9\% were involved in proteostasis and 6.4\% in metabolism, 12.7\% were cell surface-associated proteins, 11.9\% were assigned to other functions, and 20.6\% represented genes of unknown function. For 40\% of the identified genes there has as yet not been any protein evidence. For a subset of 27 genes, transcript changes during gametogenesis were studied in detail by real-time RT-PCR. Of these, 22 genes were expressed in gametocytes, and for 15 genes transcript expression in gametocytes was increased compared to asexual blood stage parasites. Transcript levels of seven genes were particularly high in activated gametocytes, pointing at functions downstream of gametocyte transmission to the mosquito. For selected genes, a regulated expression during gametogenesis was confirmed on the protein level, using quantitative confocal microscopy. Conclusions: The obtained transcriptome data demonstrate the regulations of gene expression immediately following malaria parasite transmission to the mosquito. Our findings support the identification of proteins important for sexual reproduction and further development of the mosquito midgut stages and provide insights into the genetic basis of the rapid adaption of Plasmodium to the insect vector.}, language = {en} } @article{WirthGlushakovaScheuermayeretal.2014, author = {Wirth, Christine C. and Glushakova, Svetlana and Scheuermayer, Matthias and Repnik, Urska and Garg, Swatl and Schaack, Dominik and Kachman, Marika M. and Weißbach, Tim and Zimmerberg, Joshua and Dandekar, Thomas and Griffiths, Gareth and Chitnis, Chetan E. and Singh, Shallja and Fischer, Rainer and Pradel, Gabriele}, title = {Perforin-like protein PPLP2 permeabilizes the red blood cell membrane during egress of Plasmodium falciparum gametocytes}, series = {Cellular Microbiology}, volume = {16}, journal = {Cellular Microbiology}, number = {5}, doi = {10.1111/cmi.12288}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-120895}, pages = {709-33}, year = {2014}, abstract = {Egress of malaria parasites from the host cell requires the concerted rupture of its enveloping membranes. Hence, we investigated the role of the plasmodial perforin-like protein PPLP2 in the egress of Plasmodium falciparum from erythrocytes. PPLP2 is expressed in blood stage schizonts and mature gametocytes. The protein localizes in vesicular structures, which in activated gametocytes discharge PPLP2 in a calcium-dependent manner. PPLP2 comprises a MACPF domain and recombinant PPLP2 has haemolytic activities towards erythrocytes. PPLP2-deficient [PPLP2(-)] merozoites show normal egress dynamics during the erythrocytic replication cycle, but activated PPLP2(-) gametocytes were unable to leave erythrocytes and stayed trapped within these cells. While the parasitophorous vacuole membrane ruptured normally, the activated PPLP2(-) gametocytes were unable to permeabilize the erythrocyte membrane and to release the erythrocyte cytoplasm. In consequence, transmission of PPLP2(-) parasites to the Anopheles vector was reduced. Pore-forming equinatoxin II rescued both PPLP2(-) gametocyte exflagellation and parasite transmission. The pore sealant Tetronic 90R4, on the other hand, caused trapping of activated wild-type gametocytes within the enveloping erythrocytes, thus mimicking the PPLP2(-) loss-of-function phenotype. We propose that the haemolytic activity of PPLP2 is essential for gametocyte egress due to permeabilization of the erythrocyte membrane and depletion of the erythrocyte cytoplasm.}, language = {en} } @article{FellerThomKochetal.2013, author = {Feller, Tatjana and Thom, Pascal and Koch, Natalie and Spiegel, Holger and Addai-Mensah, Otchere and Fischer, Rainer and Reimann, Andreas and Pradel, Gabriele and Fendel, Rolf and Schillberg, Stefan and Scheuermayer, Matthias and Schinkel, Helga}, title = {Plant-Based Production of Recombinant Plasmodium Surface Protein Pf38 and Evaluation of its Potential as a Vaccine Candidate}, series = {PLOS ONE}, volume = {8}, journal = {PLOS ONE}, number = {11}, issn = {1932-6203}, doi = {10.1371/journal.pone.0079920}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-128221}, pages = {e79920}, year = {2013}, abstract = {Pf38 is a surface protein of the malarial parasite Plasmodium falciparum. In this study, we produced and purified recombinant Pf38 and a fusion protein composed of red fluorescent protein and Pf38 (RFP-Pf38) using a transient expression system in the plant Nicotiana benthamiana. To our knowledge, this is the first description of the production of recombinant Pf38. To verify the quality of the recombinant Pf38, plasma from semi-immune African donors was used to confirm specific binding to Pf38. ELISA measurements revealed that immune responses to Pf38 in this African subset were comparable to reactivities to AMA-1 and \(MSP1_{19}\). Pf38 and RFP-Pf38 were successfully used to immunise mice, although titres from these mice were low (on average 1:11.000 and 1:39.000, respectively). In immune fluorescence assays, the purified IgG fraction from the sera of immunised mice recognised Pf38 on the surface of schizonts, gametocytes, macrogametes and zygotes, but not sporozoites. Growth inhibition assays using \(\alpha Pf38\) antibodies demonstrated strong inhibition \((\geq 60 \\% ) \) of the growth of blood-stage P. falciparum. The development of zygotes was also effectively inhibited by \(\alpha Pf38\) antibodies, as determined by the zygote development assay. Collectively, these results suggest that Pf38 is an interesting candidate for the development of a malaria vaccine.}, language = {en} } @article{WinklerFischerSchadeetal.2015, author = {Winkler, Karol and Fischer, Julian and Schade, Anne and Amthor, Matthias and Dall, Robert and Geßler, Jonas and Emmerling, Monika and Ostrovskaya, Elena A. and Kamp, Martin and Schneider, Christian and H{\"o}fling, Sven}, title = {A polariton condensate in a photonic crystal potential landscape}, series = {New Journal of Physics}, volume = {17}, journal = {New Journal of Physics}, doi = {10.1088/1367-2630/17/2/023001}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-125050}, pages = {023001}, year = {2015}, abstract = {The possibility of investigating macroscopic coherent quantum states in polariton condensates and of engineering polariton landscapes in semiconductors has triggered interest in using polaritonic systems to simulate complex many-body phenomena. However, advanced experiments require superior trapping techniques that allow for the engineering of periodic and arbitrary potentials with strong on-site localization, clean condensate formation, and nearest-neighbor coupling. Here we establish a technology that meets these demands and enables strong, potentially tunable trapping without affecting the favorable polariton characteristics. The traps are based on a locally elongated microcavity which can be formed by standard lithography. We observe polariton condensation with non-resonant pumping in single traps and photonic crystal square lattice arrays. In the latter structures, we observe pronounced energy bands, complete band gaps, and spontaneous condensation at the M-point of the Brillouin zone.}, language = {en} } @article{BeissSpiegelBoesetal.2015, author = {Beiss, Veronique and Spiegel, Holger and Boes, Alexander and Scheuermayer, Matthias and Reimann, Andreas and Schillberg, Stefan and Fischer, Rainer}, title = {Plant expression and characterization of the transmission-blocking vaccine candidate PfGAP50}, series = {BMC Biotechnology}, volume = {15}, journal = {BMC Biotechnology}, number = {108}, doi = {10.1186/s12896-015-0225-x}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-137327}, year = {2015}, abstract = {Background: Despite the limited success after decades of intensive research and development efforts, vaccination still represents the most promising strategy to significantly reduce the disease burden in malaria endemic regions. Besides the ultimate goal of inducing sterile protection in vaccinated individuals, the prevention of transmission by so-called transmission blocking vaccines (TBVs) is being regarded as an important feature of an efficient malaria eradication strategy. Recently, Plasmodium falciparum GAP50 (PfGAP50), a 44.6 kDa transmembrane protein that forms an essential part of the invasion machinery (glideosome) multi-protein complex, has been proposed as novel potential transmission-blocking candidate. Plant-based expression systems combine the advantages of eukaryotic expression with a up-scaling potential and a good product safety profile suitable for vaccine production. In this study we investigated the feasibility to use the transient plant expression to produce PfGAP50 suitable for the induction of parasite specific inhibitory antibodies. Results: We performed the transient expression of recombinant PfGAP50 in Nicotiana benthamiana leaves using endoplasmatic reticulum (ER) and plastid targeting. After IMAC-purification the protein yield and integrity was investigated by SDS-PAGE and Western Blot. Rabbit immune IgG derived by the immunization with the plastidtargeted variant of PfGAP50 was analyzed by immune fluorescence assay (IFA) and zygote inhibition assay (ZIA). PfGAP50 could be produced in both subcellular compartments at different yields IMAC (Immobilized Metal Affinity Chromatography) purification from extract yielded up to 4.1 mu g/g recombinant protein per fresh leaf material for ER-retarded and 16.2 mu g/g recombinant protein per fresh leave material for plasmid targeted PfGAP50, respectively. IgG from rabbit sera generated by immunization with the recombinant protein specifically recognized different parasite stages in immunofluorescence assay. Furthermore up to 55 \% inhibition in an in vitro zygote inhibition assay could be achieved using PfGAP50-specific rabbit immune IgG. Conclusions: The results of this study demonstrate that the plant-produced PfGAP50 is functional regarding the presentation of inhibitory epitopes and could be considered as component of a transmission-blocking malaria vaccine formulation.}, language = {en} } @article{MorrisCarusoBuscotetal.2014, author = {Morris, E. Kathryn and Caruso, Tancredi and Buscot, Francois and Fischer, Markus and Hancock, Christine and Maier, Tanja S. and Meiners, Torsten and M{\"u}ller, Caroline and Obermaier, Elisabeth and Prati, Daniel and Socher, Stephanie A. and Sonnemann, Ilja and W{\"a}schke, Nicola and Wubet, Tesfaye and Wurst, Susanne and Rillig, Matthias C.}, title = {Choosing and using diversity indices: insights for ecological applications from the German Biodiversity Exploratories}, series = {Ecology and Evolution}, volume = {4}, journal = {Ecology and Evolution}, number = {18}, issn = {2045-7758}, doi = {10.1002/ece3.1155}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-115462}, pages = {3514-3524}, year = {2014}, abstract = {Biodiversity, a multidimensional property of natural systems, is difficult to quantify partly because of the multitude of indices proposed for this purpose. Indices aim to describe general properties of communities that allow us to compare different regions, taxa, and trophic levels. Therefore, they are of fundamental importance for environmental monitoring and conservation, although there is no consensus about which indices are more appropriate and informative. We tested several common diversity indices in a range of simple to complex statistical analyses in order to determine whether some were better suited for certain analyses than others. We used data collected around the focal plant Plantago lanceolata on 60 temperate grassland plots embedded in an agricultural landscape to explore relationships between the common diversity indices of species richness (S), Shannon's diversity (H'), Simpson's diversity (D-1), Simpson's dominance (D-2), Simpson's evenness (E), and Berger-Parker dominance (BP). We calculated each of these indices for herbaceous plants, arbuscular mycorrhizal fungi, aboveground arthropods, belowground insect larvae, and P.lanceolata molecular and chemical diversity. Including these trait-based measures of diversity allowed us to test whether or not they behaved similarly to the better studied species diversity. We used path analysis to determine whether compound indices detected more relationships between diversities of different organisms and traits than more basic indices. In the path models, more paths were significant when using H', even though all models except that with E were equally reliable. This demonstrates that while common diversity indices may appear interchangeable in simple analyses, when considering complex interactions, the choice of index can profoundly alter the interpretation of results. Data mining in order to identify the index producing the most significant results should be avoided, but simultaneously considering analyses using multiple indices can provide greater insight into the interactions in a system.}, language = {en} } @phdthesis{Fischer2004, author = {Fischer, Matthias}, title = {Lokalisierung eines Ged{\"a}chtnisses bei Drosophila melanogaster}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-8050}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2004}, abstract = {Es konnte in dieser Arbeit gezeigt werden, daß das olfaktorische Kurzzeitged{\"a}chtnis von Drosophila melanogaster in den Pilzk{\"o}rpern lokalisiert ist. Zu Beginn dieser Doktorarbeit war bekannt, daß die Pilzk{\"o}rper notwendig f{\"u}r das Geruchsged{\"a}chtnis sind. Drei unabh{\"a}ngige Methoden der Ablation bzw. Ver{\"a}nderung der biochemischen Eigenschaften der Pilzk{\"o}rper hatten zu dem selben Ergebnis gef{\"u}hrt, daß funktionierende Pilzk{\"o}rper unentbehrlich f{\"u}r den Aufbau eines Geruchsged{\"a}chtnisses sind. Noch informativer als ein Experiment, in dem durch Zerst{\"o}rung einer Struktur eine Leistung unm{\"o}glich gemacht wird ist der umgekehrte Weg, der durch einen gewebespezifischen „rescue" die Leistung wiederherstellt. Dazu wurde in dieser Arbeit das wildtypische Allel des Gens rutabaga in rut-mutanten Fliegen mit Hilfe des Gal4/UAS-Systems ausschließlich in den Pilzk{\"o}rpern, bzw., im Gegenexperiment, nur außerhalb der Pilzk{\"o}rper zur Expression gebracht. rut kodiert f{\"u}r die Adenylatcyclase I, die mit synaptischer Plastizit{\"a}t bei Drosophila, Aplysia und M{\"a}usen in Verbindung gebracht wird. Man geht davon aus, daß synaptische Plastizit{\"a}t die molekulare Grundlage f{\"u}r Lernen und Ged{\"a}chtnis ist. Die AC I stellt cAMP her, dessen Menge und pr{\"a}zise Regulation die {\"U}bertragungsst{\"a}rke an Neuronen beeinflußt. Eine St{\"o}rung dieses Signalweges z. B. durch die rut-Mutation f{\"u}hrt zu einer Beeintr{\"a}chtigung des Ged{\"a}chtnisses bei Drosophila. rut wurde mit Hilfe des in Drosophila etablierten Gal4/UAS-Systems exprimiert: Der gewebespezifisch aktive Hefe-Transkriptionsfaktor Gal4 f{\"u}hrt dazu, daß das hinter einen Gal4-spezifischen UAS-Promotor klonierte wildtypische rut-Gen in denjenigen Zellen transkribiert wird, in denen der Transkriptionsfaktor vorhanden ist. Dies wurde in einer rut-Mutante durchgef{\"u}hrt, so daß in allen anderen Zellen keine funktionierende AC I vorhanden war. Die rut-abh{\"a}ngige synaptische Plastizit{\"a}t wurde damit ausschließlich auf die gew{\"u}nschten Regionen beschr{\"a}nkt. Das Expressionsmuster der Gal4-Linien wurde durch Immuncytochemie (Anti-Tau) sichtbar gemacht. Diese Fliegen wurden in einem klassischen Konditionierungsexperiment auf ihr Geruchs-Ged{\"a}chtnis untersucht. Dazu wurden einer Gruppe von Fliegen nacheinander 2 Ger{\"u}che pr{\"a}sentiert, von denen einer mit Elektroschocks gepaart war. Nach ca. 2 min konnten diese Fliegen sich f{\"u}r einen der beiden Ger{\"u}che entscheiden, die nun gleichzeitig aus 2 unterschiedlichen Richtungen dargeboten wurden. Je nach Lernleistung entschieden sich mehr oder weniger Fliegen f{\"u}r den vorher unbestraften Geruch. Es ergab sich, daß der Ort im Gehirn, an dem die wildtypische AC I exprimiert wurde, {\"u}ber die H{\"o}he des Ged{\"a}chtniswertes entschied: Die AC I ausschließlich in den Pilzk{\"o}rpern gew{\"a}hrte ein v{\"o}llig normales Ged{\"a}chtnis, wogegen die AC I außerhalb der Pilzk{\"o}rper das Ged{\"a}chtnis nicht gegen{\"u}ber der rut-Mutante verbessern konnte. Die Analyse der Expressionsverteilung von insgesamt 9 getesteten Fliegenlinien mißt {\"u}berdies dem \&\#61543;-Lobus des Pilzk{\"o}rpers eine besondere Bedeutung bei und l{\"a}ßt den Schluß zu, daß das hier untersuchte Ged{\"a}chtnis ausschließlich in den \&\#61543;-Loben lokalisiert ist. Dieses erfolgreiche rut-„rescue" - Experiment zeigt, daß rut-abh{\"a}ngige synaptische Plastizit{\"a}t ausschließlich in den Pilzk{\"o}rpern ausreichend f{\"u}r ein wildtypisches Ged{\"a}chtnis ist. Dieses Ergebnis vervollst{\"a}ndigt die Erkenntnisse von den Pilzk{\"o}rper-Ablationsexperimenten insofern, als nun die Aussage zutrifft, daß die Pilzk{\"o}rper notwendig und hinreichend f{\"u}r das olfaktorische Kurzzeitged{\"a}chtnis sind.}, language = {de} } @phdthesis{Fischer2010, author = {Fischer, Matthias}, title = {Der Einfluß der Ribosomale S6 Kinase 2 (RSK2) auf das Neuriten- und Synapsenwachstum in vivo und in Zellkultur}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-48341}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2010}, abstract = {In dieser Arbeit sollte die Funktion der Ribosomalen S6 Kinase 2 (RSK2) auf neuronaler Ebene untersucht werden. Dahingehend gab es, z.B. auf Grund der Ph{\"a}notypen von Fliegen und M{\"a}usen mit Mutationen im entsprechenden Gen oder von Patienten mit Coffin-Lowry-Syndrom (CLS) nur Vermutungen. Es bestand letztlich die Hoffnung, einen Beitrag zur Aufkl{\"a}rung der Pathophysiologie des CLS zu leisten. Es stellte sich auf Grund von Experimenten sowohl in vivo als auch in vitro in verschiedenen Modellsystemen in dieser Arbeit heraus, daß RSK2 einen negativen Einfluß auf das Neuriten- und Synapsenwachstum hat. In kultivierten Motoneuronen f{\"u}hrte der KO von RSK2 zu l{\"a}ngeren Axonen und die {\"U}berexpression eines konstitutiv aktiven RSK2-Konstrukts zu k{\"u}rzeren Axonen. In PC12-Zellen f{\"u}hrte die Expression von konstitutiv aktiven RSK2 Konstrukten zur Verk{\"u}rzung der Neuriten und die Expression eines Kinase-inaktiven RSK2 Konstrukts zu l{\"a}ngeren Neuriten. In vivo war die neuromuskul{\"a}re Synapse bei RSK2-KO M{\"a}usen vergr{\"o}ßert und hatte bei Drosophila rsk Mutanten mehr Boutons. Das RSK2-Protein ist in Motoneuronen der Maus und in {\"u}berexprimierter Form in den Boutons der neuromuskul{\"a}ren Synapse bei Drosophila nachweisbar. Damit wurde zum ersten Mal die Funktion von RSK2 auf neuronaler Ebene beschrieben. Bez{\"u}glich des Mechanismus, wie RSK2 das Nervenwachstum beeinflußt gab es deutliche Hinweise, die daf{\"u}r sprechen, daß RSK2 dies {\"u}ber eine in der Literatur schon h{\"a}ufiger beschriebene Hemmung der MAPK ERK1/2 erreicht. F{\"u}r diese Hypothese spricht die Tatsache, daß die ERK-Phosphorylierung in murinen Motoneuronen und im R{\"u}ckenmark embryonaler M{\"a}use der RSK2-Mutante erh{\"o}ht ist und der Axonwachstumsdefekt durch eine Hemmung von MEK/ERK behoben werden kann. Auch ist die ERK-Phosphorylierung an der murinen Muskel-Endplatte in der Mutante erh{\"o}ht. Zudem zeigen genetische Epistasis-Experimente in Drosophila, daß RSK die Bouton-Zahl {\"u}ber ERK/RL hemmt. RSK scheint also in Drosophila von der Funktion her der RSK2-Isoform in Wirbeltieren sehr {\"a}hnlich zu sein. Ein weiteres wichtiges Ergebnis ist die Beobachtung, daß RSK2 bei Motoneuronen keinen wesentlichen Einfluß auf das {\"U}berleben der Zellen in Gegenwart neurotropher Faktoren hat. M{\"o}glicherweise spielen hier redundante Funktionen der RSK Familienmitglieder eine Rolle. Ein bislang unerkl{\"a}rter Befund ist die reduzierte Frequenz spontaner Depolarisationen bzw. damit einhergehender Ca2+ Einstr{\"o}me bei RSK2-KO Motoneuronen in Zellkultur. Die H{\"a}ufigkeit und Dichte von Ca2+-Kan{\"a}len und aktive Zonen Proteinen war in Motoneuronen nicht von der Anwesenheit des RSK2-Proteins abh{\"a}ngig. Im Hippocampus konnte außerdem das RSK2-Protein pr{\"a}synaptisch in den Moosfaser-Boutons der CA3 Region nachgewiesen werden. Es befindet sich auch in den Pyramidenzellen, aber nicht in den Pyramidenzell-Dendriten in CA3. Bez{\"u}glich der Bedeutung dieser Befunde f{\"u}r die Aufkl{\"a}rung der Pathologie des CLS ist zu folgern, daß der neuro-psychologische Ph{\"a}notyp bei CLS Patienten wahrscheinlich nicht durch reduziertes {\"U}berleben von Neuronen, sondern eher durch disinhibiertes Axonwachstum oder Synapsenwachstum bedingt ist. Dies kann grob sowohl f{\"u}r die peripheren als auch die zentralen Defekte gelten, denn die Synapsen im ZNS und am Muskel sind in ihrer molekularen Ausstattung z.B. im Bereich der Vesikel, der aktiven Zonen oder der Transmitteraussch{\"u}ttung sehr {\"a}hnlich. Weiterhin k{\"o}nnte eine ver{\"a}nderte synaptische Plastizit{\"a}t u.a. an der Moosfaser-Pyramidenzell-Synapse in der CA3 Region des Hippocampus eine Rolle bei den kognitiven und mnestischen Einschr{\"a}nkungen der Patienten spielen. Die Entdeckung, daß aktiviertes ERK bei den beobachteten Effekten eine Rolle spielt kann f{\"u}r die Entwicklung von Therapiestrategien eine wertvolle Erkenntnis sein.}, subject = {Ribosom}, language = {de} } @article{PolatKaiserWohllebenetal.2017, author = {Polat, B{\"u}lent and Kaiser, Philipp and Wohlleben, Gisela and Gehrke, Thomas and Scherzad, Agmal and Scheich, Matthias and Malzahn, Uwe and Fischer, Thomas and Vordermark, Dirk and Flentje, Michael}, title = {Perioperative changes in osteopontin and TGFβ1 plasma levels and their prognostic impact for radiotherapy in head and neck cancer}, series = {BMC Cancer}, volume = {17}, journal = {BMC Cancer}, number = {6}, doi = {10.1186/s12885-016-3024-4}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-157529}, year = {2017}, abstract = {Background: In head and neck cancer little is known about the kinetics of osteopontin (OPN) expression after tumor resection. In this study we evaluated the time course of OPN plasma levels before and after surgery. Methods: Between 2011 and 2013 41 consecutive head and neck cancer patients were enrolled in a prospective study (group A). At different time points plasma samples were collected: T0) before, T1) 1 day, T2) 1 week and T3) 4 weeks after surgery. Osteopontin and TGFβ1 plasma concentrations were measured with a commercial ELISA system. Data were compared to 131 head and neck cancer patients treated with primary (n = 42) or postoperative radiotherapy (n = 89; group B1 and B2). Results: A significant OPN increase was seen as early as 1 day after surgery (T0 to T1, p < 0.01). OPN levels decreased to base line 3-4 weeks after surgery. OPN values were correlated with postoperative TGFβ1 expression suggesting a relation to wound healing. Survival analysis showed a significant benefit for patients with lower OPN levels both in the primary and postoperative radiotherapy group (B1: 33 vs 11.5 months, p = 0.017, B2: median not reached vs 33.4, p = 0.031). TGFβ1 was also of prognostic significance in group B1 (33.0 vs 10.7 months, p = 0.003). Conclusions: Patients with head and neck cancer showed an increase in osteopontin plasma levels directly after surgery. Four weeks later OPN concentration decreased to pre-surgery levels. This long lasting increase was presumably associated to wound healing. Both pretherapeutic osteopontin and TGFβ1 had prognostic impact.}, language = {en} } @article{HahnBeudertGutmannetal.2021, author = {Hahn, Lukas and Beudert, Matthias and Gutmann, Marcus and Keßler, Larissa and Stahlhut, Philipp and Fischer, Lena and Karakaya, Emine and Lorson, Thomas and Thievessen, Ingo and Detsch, Rainer and L{\"u}hmann, Tessa and Luxenhofer, Robert}, title = {From Thermogelling Hydrogels toward Functional Bioinks: Controlled Modification and Cytocompatible Crosslinking}, series = {Macromolecular Bioscience}, volume = {21}, journal = {Macromolecular Bioscience}, number = {10}, doi = {10.1002/mabi.202100122}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-257542}, year = {2021}, abstract = {Hydrogels are key components in bioink formulations to ensure printability and stability in biofabrication. In this study, a well-known Diels-Alder two-step post-polymerization modification approach is introduced into thermogelling diblock copolymers, comprising poly(2-methyl-2-oxazoline) and thermoresponsive poly(2-n-propyl-2-oxazine). The diblock copolymers are partially hydrolyzed and subsequently modified by acid/amine coupling with furan and maleimide moieties. While the thermogelling and shear-thinning properties allow excellent printability, trigger-less cell-friendly Diels-Alder click-chemistry yields long-term shape-fidelity. The introduced platform enables easy incorporation of cell-binding moieties (RGD-peptide) for cellular interaction. The hydrogel is functionalized with RGD-peptides using thiol-maleimide chemistry and cell proliferation as well as morphology of fibroblasts seeded on top of the hydrogels confirm the cell adhesion facilitated by the peptides. Finally, bioink formulations are tested for biocompatibility by incorporating fibroblasts homogenously inside the polymer solution pre-printing. After the printing and crosslinking process good cytocompatibility is confirmed. The established bioink system combines a two-step approach by physical precursor gelation followed by an additional chemical stabilization, offering a broad versatility for further biomechanical adaptation or bioresponsive peptide modification.}, language = {en} } @article{JiBaderRamanathanetal.2021, author = {Ji, Changhe and Bader, Jakob and Ramanathan, Pradhipa and Hennlein, Luisa and Meissner, Felix and Jablonka, Sibylle and Mann, Matthias and Fischer, Utz and Sendtner, Michael and Briese, Michael}, title = {Interaction of 7SK with the Smn complex modulates snRNP production}, series = {Nature Communications}, volume = {12}, journal = {Nature Communications}, number = {1}, doi = {10.1038/s41467-021-21529-1}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-259125}, pages = {1278}, year = {2021}, abstract = {Gene expression requires tight coordination of the molecular machineries that mediate transcription and splicing. While the interplay between transcription kinetics and spliceosome fidelity has been investigated before, less is known about mechanisms regulating the assembly of the spliceosomal machinery in response to transcription changes. Here, we report an association of the Smn complex, which mediates spliceosomal snRNP biogenesis, with the 7SK complex involved in transcriptional regulation. We found that Smn interacts with the 7SK core components Larp7 and Mepce and specifically associates with 7SK subcomplexes containing hnRNP R. The association between Smn and 7SK complexes is enhanced upon transcriptional inhibition leading to reduced production of snRNPs. Taken together, our findings reveal a functional association of Smn and 7SK complexes that is governed by global changes in transcription. Thus, in addition to its canonical nuclear role in transcriptional regulation, 7SK has cytosolic functions in fine-tuning spliceosome production according to transcriptional demand.}, language = {en} } @article{PetersHempAppelhansetal.2016, author = {Peters, Marcell K. and Hemp, Andreas and Appelhans, Tim and Behler, Christina and Classen, Alice and Detsch, Florian and Ensslin, Andreas and Ferger, Stefan W. and Frederiksen, Sara B. and Gebert, Frederike and Haas, Michael and Helbig-Bonitz, Maria and Hemp, Claudia and Kindeketa, William J. and Mwangomo, Ephraim and Ngereza, Christine and Otte, Insa and R{\"o}der, Juliane and Rutten, Gemma and Costa, David Schellenberger and Tardanico, Joseph and Zancolli, Giulia and Deckert, J{\"u}rgen and Eardley, Connal D. and Peters, Ralph S. and R{\"o}del, Mark-Oliver and Schleuning, Matthias and Ssymank, Axel and Kakengi, Victor and Zhang, Jie and B{\"o}hning-Gaese, Katrin and Brandl, Roland and Kalko, Elisabeth K.V. and Kleyer, Michael and Nauss, Thomas and Tschapka, Marco and Fischer, Markus and Steffan-Dewenter, Ingolf}, title = {Predictors of elevational biodiversity gradients change from single taxa to the multi-taxa community level}, series = {Nature Communications}, volume = {7}, journal = {Nature Communications}, doi = {10.1038/ncomms13736}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-169374}, year = {2016}, abstract = {The factors determining gradients of biodiversity are a fundamental yet unresolved topic in ecology. While diversity gradients have been analysed for numerous single taxa, progress towards general explanatory models has been hampered by limitations in the phylogenetic coverage of past studies. By parallel sampling of 25 major plant and animal taxa along a 3.7 km elevational gradient on Mt. Kilimanjaro, we quantify cross-taxon consensus in diversity gradients and evaluate predictors of diversity from single taxa to a multi-taxa community level. While single taxa show complex distribution patterns and respond to different environmental factors, scaling up diversity to the community level leads to an unambiguous support for temperature as the main predictor of species richness in both plants and animals. Our findings illuminate the influence of taxonomic coverage for models of diversity gradients and point to the importance of temperature for diversification and species coexistence in plant and animal communities.}, language = {en} } @article{BoesSpiegelVoepeletal.2015, author = {Boes, Alexander and Spiegel, Holger and Voepel, Nadja and Edgue, Gueven and Beiss, Veronique and Kapelski, Stephanie and Fendel, Rolf and Scheuermayer, Matthias and Pradel, Gabriele and Bolscher, Judith M. and Behet, Marije C. and Dechering, Koen J. and Hermsen, Cornelus C. and Sauerwein, Robert W. and Schillberg, Stefan and Reimann, Andreas and Fischer, Rainer}, title = {Analysis of a multi-component multi-stage malaria vaccine candidate—tackling the cocktail challenge}, series = {PLoS ONE}, volume = {10}, journal = {PLoS ONE}, number = {7}, doi = {10.1371/journal.pone.0131456}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-173092}, pages = {e0131456}, year = {2015}, abstract = {Combining key antigens from the different stages of the P. falciparum life cycle in the context of a multi-stage-specific cocktail offers a promising approach towards the development of a malaria vaccine ideally capable of preventing initial infection, the clinical manifestation as well as the transmission of the disease. To investigate the potential of such an approach we combined proteins and domains (11 in total) from the pre-erythrocytic, blood and sexual stages of P. falciparum into a cocktail of four different components recombinantly produced in plants. After immunization of rabbits we determined the domain-specific antibody titers as well as component-specific antibody concentrations and correlated them with stage specific in vitro efficacy. Using purified rabbit immune IgG we observed strong inhibition in functional in vitro assays addressing the pre-erythrocytic (up to 80\%), blood (up to 90\%) and sexual parasite stages (100\%). Based on the component-specific antibody concentrations we calculated the IC50 values for the pre-erythrocytic stage (17-25 μg/ml), the blood stage (40-60 μg/ml) and the sexual stage (1.75 μg/ml). While the results underline the feasibility of a multi-stage vaccine cocktail, the analysis of component-specific efficacy indicates significant differences in IC50 requirements for stage-specific antibody concentrations providing valuable insights into this complex scenario and will thereby improve future approaches towards malaria vaccine cocktail development regarding the selection of suitable antigens and the ratios of components, to fine tune overall and stage-specific efficacy.}, language = {en} } @article{RiveroAlhamaRibaKuetal.2021, author = {Rivero, Olga and Alhama-Riba, Judit and Ku, Hsing-Ping and Fischer, Matthias and Ortega, Gabriela and {\´A}lmos, P{\´e}ter and Diouf, David and van den Hove, Daniel and Lesch, Klaus-Peter}, title = {Haploinsufficiency of the Attention-Deficit/Hyperactivity Disorder Risk Gene St3gal3 in Mice Causes Alterations in Cognition and Expression of Genes Involved in Myelination and Sialylation}, series = {Frontiers in Genetics}, volume = {12}, journal = {Frontiers in Genetics}, issn = {1664-8021}, doi = {10.3389/fgene.2021.688488}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-246855}, year = {2021}, abstract = {Genome wide association meta-analysis identified ST3GAL3, a gene encoding the beta-galactosidase-alpha-2,3-sialyltransferase-III, as a risk gene for attention-deficit/hyperactivity disorder (ADHD). Although loss-of-function mutations in ST3GAL3 are implicated in non-syndromic autosomal recessive intellectual disability (NSARID) and West syndrome, the impact of ST3GAL3 haploinsufficiency on brain function and the pathophysiology of neurodevelopmental disorders (NDDs), such as ADHD, is unknown. Since St3gal3 null mutant mice display severe developmental delay and neurological deficits, we investigated the effects of partial inactivation of St3gal3 in heterozygous (HET) knockout (St3gal3±) mice on behavior as well as expression of markers linked to myelination processes and sialylation pathways. Our results reveal that male St3gal3 HET mice display cognitive deficits, while female HET animals show increased activity, as well as increased cognitive control, compared to their wildtype littermates. In addition, we observed subtle alterations in the expression of several markers implicated in oligodendrogenesis, myelin formation, and protein sialylation as well as cell adhesion/synaptic target glycoproteins of ST3GAL3 in a brain region- and/or sex-specific manner. Taken together, our findings indicate that haploinsufficiency of ST3GAL3 results in a sex-dependent alteration of cognition, behavior and markers of brain plasticity.}, language = {en} } @article{FarmerStrzelczykFinisguerraetal.2021, author = {Farmer, Adam D. and Strzelczyk, Adam and Finisguerra, Alessandra and Gourine, Alexander V. and Gharabaghi, Alireza and Hasan, Alkomiet and Burger, Andreas M. and Jaramillo, Andr{\´e}s M. and Mertens, Ann and Majid, Arshad and Verkuil, Bart and Badran, Bashar W. and Ventura-Bort, Carlos and Gaul, Charly and Beste, Christian and Warren, Christopher M. and Quintana, Daniel S. and H{\"a}mmerer, Dorothea and Freri, Elena and Frangos, Eleni and Tobaldini, Eleonora and Kaniusas, Eugenijus and Rosenow, Felix and Capone, Fioravante and Panetsos, Fivos and Ackland, Gareth L. and Kaithwas, Gaurav and O'Leary, Georgia H. and Genheimer, Hannah and Jacobs, Heidi I. L. and Van Diest, Ilse and Schoenen, Jean and Redgrave, Jessica and Fang, Jiliang and Deuchars, Jim and Sz{\´e}les, Jozsef C. and Thayer, Julian F. and More, Kaushik and Vonck, Kristl and Steenbergen, Laura and Vianna, Lauro C. and McTeague, Lisa M. and Ludwig, Mareike and Veldhuizen, Maria G. and De Couck, Marijke and Casazza, Marina and Keute, Marius and Bikson, Marom and Andreatta, Marta and D'Agostini, Martina and Weymar, Mathias and Betts, Matthew and Prigge, Matthias and Kaess, Michael and Roden, Michael and Thai, Michelle and Schuster, Nathaniel M. and Montano, Nicola and Hansen, Niels and Kroemer, Nils B. and Rong, Peijing and Fischer, Rico and Howland, Robert H. and Sclocco, Roberta and Sellaro, Roberta and Garcia, Ronald G. and Bauer, Sebastian and Gancheva, Sofiya and Stavrakis, Stavros and Kampusch, Stefan and Deuchars, Susan A. and Wehner, Sven and Laborde, Sylvain and Usichenko, Taras and Polak, Thomas and Zaehle, Tino and Borges, Uirassu and Teckentrup, Vanessa and Jandackova, Vera K. and Napadow, Vitaly and Koenig, Julian}, title = {International Consensus Based Review and Recommendations for Minimum Reporting Standards in Research on Transcutaneous Vagus Nerve Stimulation (Version 2020)}, series = {Frontiers in Human Neuroscience}, volume = {14}, journal = {Frontiers in Human Neuroscience}, issn = {1662-5161}, doi = {10.3389/fnhum.2020.568051}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-234346}, year = {2021}, abstract = {Given its non-invasive nature, there is increasing interest in the use of transcutaneous vagus nerve stimulation (tVNS) across basic, translational and clinical research. Contemporaneously, tVNS can be achieved by stimulating either the auricular branch or the cervical bundle of the vagus nerve, referred to as transcutaneous auricular vagus nerve stimulation(VNS) and transcutaneous cervical VNS, respectively. In order to advance the field in a systematic manner, studies using these technologies need to adequately report sufficient methodological detail to enable comparison of results between studies, replication of studies, as well as enhancing study participant safety. We systematically reviewed the existing tVNS literature to evaluate current reporting practices. Based on this review, and consensus among participating authors, we propose a set of minimal reporting items to guide future tVNS studies. The suggested items address specific technical aspects of the device and stimulation parameters. We also cover general recommendations including inclusion and exclusion criteria for participants, outcome parameters and the detailed reporting of side effects. Furthermore, we review strategies used to identify the optimal stimulation parameters for a given research setting and summarize ongoing developments in animal research with potential implications for the application of tVNS in humans. Finally, we discuss the potential of tVNS in future research as well as the associated challenges across several disciplines in research and clinical practice.}, language = {en} } @article{FischerRaabe2018, author = {Fischer, Matthias and Raabe, Thomas}, title = {Animal models for Coffin-Lowry syndrome: RSK2 and nervous system dysfunction}, series = {Frontiers in Behavioral Neuroscience}, volume = {12}, journal = {Frontiers in Behavioral Neuroscience}, number = {106}, doi = {10.3389/fnbeh.2018.00106}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-176799}, year = {2018}, abstract = {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.}, language = {en} } @article{FischerHeinrichs2018, author = {Fischer, Matthias and Heinrichs, Harald}, title = {Dimensions, dialectic, discourse. Three political perspectives on the sustainability of the German healthcare system}, series = {International Journal of Environmental Research and Public Health}, volume = {15}, journal = {International Journal of Environmental Research and Public Health}, number = {7}, doi = {10.3390/ijerph15071526}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-177003}, pages = {1526}, year = {2018}, abstract = {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.}, language = {en} } @article{ZieglerMeyerOtteetal.2022, author = {Ziegler, Alice and Meyer, Hanna and Otte, Insa and Peters, Marcell K. and Appelhans, Tim and Behler, Christina and B{\"o}hning-Gaese, Katrin and Classen, Alice and Detsch, Florian and Deckert, J{\"u}rgen and Eardley, Connal D. and Ferger, Stefan W. and Fischer, Markus and Gebert, Friederike and Haas, Michael and Helbig-Bonitz, Maria and Hemp, Andreas and Hemp, Claudia and Kakengi, Victor and Mayr, Antonia V. and Ngereza, Christine and Reudenbach, Christoph and R{\"o}der, Juliane and Rutten, Gemma and Schellenberger Costa, David and Schleuning, Matthias and Ssymank, Axel and Steffan-Dewenter, Ingolf and Tardanico, Joseph and Tschapka, Marco and Vollst{\"a}dt, Maximilian G. R. and W{\"o}llauer, Stephan and Zhang, Jie and Brandl, Roland and Nauss, Thomas}, title = {Potential of airborne LiDAR derived vegetation structure for the prediction of animal species richness at Mount Kilimanjaro}, series = {Remote Sensing}, volume = {14}, journal = {Remote Sensing}, number = {3}, issn = {2072-4292}, doi = {10.3390/rs14030786}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-262251}, year = {2022}, abstract = {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.}, language = {en} } @article{GuneschHoffmannKiermeieretal.2020, author = {Gunesch, Sandra and Hoffmann, Matthias and Kiermeier, Carolina and Fischer, Wolfgang and Pinto, Antonio F. M. and Maurice, Tangui and Maher, Pamela and Decker, Michael}, title = {7-O-Esters of taxifolin with pronounced and overadditive effects in neuroprotection, anti-neuroinflammation, and amelioration of short-term memory impairment in vivo}, series = {Redox Biology}, volume = {29}, journal = {Redox Biology}, doi = {10.1016/j.redox.2019.101378}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-202718}, pages = {101378}, year = {2020}, abstract = {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.}, language = {en} } @article{SalehiZarePrezzaetal.2023, author = {Salehi, Saeede and Zare, Abdolhossein and Prezza, Gianluca and Bader, Jakob and Schneider, Cornelius and Fischer, Utz and Meissner, Felix and Mann, Matthias and Briese, Michael and Sendtner, Michael}, title = {Cytosolic Ptbp2 modulates axon growth in motoneurons through axonal localization and translation of Hnrnpr}, series = {Nature Communications}, volume = {14}, journal = {Nature Communications}, doi = {10.1038/s41467-023-39787-6}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-357639}, year = {2023}, abstract = {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.}, language = {en} } @article{AlbrechtClassenVollstaedtetal.2018, author = {Albrecht, J{\"o}rg and Classen, Alice and Vollst{\"a}dt, Maximilian G.R. and Mayr, Antonia and Mollel, Neduvoto P. and Schellenberger Costa, David and Dulle, Hamadi I. and Fischer, Markus and Hemp, Andreas and Howell, Kim M. and Kleyer, Michael and Nauss, Thomas and Peters, Marcell K. and Tschapka, Marco and Steffan-Dewenter, Ingolf and B{\"o}hning-Gaese, Katrin and Schleuning, Matthias}, title = {Plant and animal functional diversity drive mutualistic network assembly across an elevational gradient}, series = {Nature Communications}, volume = {9}, journal = {Nature Communications}, doi = {10.1038/s41467-018-05610-w}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-221056}, pages = {1-10}, year = {2018}, abstract = {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.}, language = {en} }