TY - JOUR A1 - Liu, Siyuan A1 - Légaré, Marc-André A1 - Seufert, Jens A1 - Prieschl, Dominic A1 - Rempel, Anna A1 - Englert, Lukas A1 - Dellermann, Theresa A1 - Paprocki, Valerie A1 - Stoy, Andreas A1 - Braunschweig, Holger T1 - 2,2′-Bipyridyl as a Redox-Active Borylene Abstraction Agent JF - Inorganic Chemistry N2 - 2,2′-Bipyridyl is shown to spontaneously abstract a borylene fragment (R–B:) from various hypovalent boron compounds. This process is a redox reaction in which the bipyridine is reduced and becomes a dianionic substituent bound to boron through its two nitrogen atoms. Various transition metal–borylene complexes and diboranes, as a well as a diborene, take part in this reaction. In the latter case, our results show an intriguing example of the homolytic cleavage of a B═B double bond. KW - Borylene KW - Heterocycles KW - Boron KW - Main-group chemistry Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-215595 N1 - This document is the unedited Author’s version of a Submitted Work that was subsequently accepted for publication in Inorganic Chemistry, copyright © American Chemical Society after peer review. To access the final edited and published work see https://doi.org/10.1021/acs.inorgchem.0c01383. VL - 59 IS - 15 ER - TY - JOUR A1 - Rauschenberger, Vera A1 - von Wardenburg, Niels A1 - Schaefer, Natascha A1 - Ogino, Kazutoyo A1 - Hirata, Hiromi A1 - Lillesaar, Christina A1 - Kluck, Christoph J. A1 - Meinck, Hans‐Michael A1 - Borrmann, Marc A1 - Weishaupt, Andreas A1 - Doppler, Kathrin A1 - Wickel, Jonathan A1 - Geis, Christian A1 - Sommer, Claudia A1 - Villmann, Carmen T1 - Glycine Receptor Autoantibodies Impair Receptor Function and Induce Motor Dysfunction JF - Annals of Neurology N2 - Objective Impairment of glycinergic neurotransmission leads to complex movement and behavioral disorders. Patients harboring glycine receptor autoantibodies suffer from stiff‐person syndrome or its severe variant progressive encephalomyelitis with rigidity and myoclonus. Enhanced receptor internalization was proposed as the common molecular mechanism upon autoantibody binding. Although functional impairment of glycine receptors following autoantibody binding has recently been investigated, it is still incompletely understood. Methods A cell‐based assay was used for positive sample evaluation. Glycine receptor function was assessed by electrophysiological recordings and radioligand binding assays. The in vivo passive transfer of patient autoantibodies was done using the zebrafish animal model. Results Glycine receptor function as assessed by glycine dose–response curves showed significantly decreased glycine potency in the presence of patient sera. Upon binding of autoantibodies from 2 patients, a decreased fraction of desensitized receptors was observed, whereas closing of the ion channel remained fast. The glycine receptor N‐terminal residues \(^{29}\)A to \(^{62}\)G were mapped as a common epitope of glycine receptor autoantibodies. An in vivo transfer into the zebrafish animal model generated a phenotype with disturbed escape behavior accompanied by a reduced number of glycine receptor clusters in the spinal cord of affected animals. Interpretation Autoantibodies against the extracellular domain mediate alterations of glycine receptor physiology. Moreover, our in vivo data demonstrate that the autoantibodies are a direct cause of the disease, because the transfer of human glycine receptor autoantibodies to zebrafish larvae generated impaired escape behavior in the animal model compatible with abnormal startle response in stiff‐person syndrome or progressive encephalitis with rigidity and myoclonus patients. KW - glycine receptor autoantibodies KW - behavioral disorders KW - neurology Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-216005 VL - 88 IS - 3 SP - 544 EP - 561 ER - TY - JOUR A1 - Weissenberger, M. A1 - Weissenberger, M. H. A1 - Gilbert, F. A1 - Groll, J. A1 - Evans, C. H. A1 - Steinert, A. F. T1 - Reduced hypertrophy in vitro after chondrogenic differentiation of adult human mesenchymal stem cells following adenoviral SOX9 gene delivery JF - BMC Musculoskeletal Disorders N2 - Background Mesenchymal stem cell (MSC) based-treatments of cartilage injury are promising but impaired by high levels of hypertrophy after chondrogenic induction with several bone morphogenetic protein superfamily members (BMPs). As an alternative, this study investigates the chondrogenic induction of MSCs via adenoviral gene-delivery of the transcription factor SOX9 alone or in combination with other inducers, and comparatively explores the levels of hypertrophy and end stage differentiation in a pellet culture system in vitro. Methods First generation adenoviral vectors encoding SOX9, TGFB1 or IGF1 were used alone or in combination to transduce human bone marrow-derived MSCs at 5 x 10\(^2\) infectious particles/cell. Thereafter cells were placed in aggregates and maintained for three weeks in chondrogenic medium. Transgene expression was determined at the protein level (ELISA/Western blot), and aggregates were analysed histologically, immunohistochemically, biochemically and by RT-PCR for chondrogenesis and hypertrophy. Results SOX9 cDNA was superior to that encoding TGFB1, the typical gold standard, as an inducer of chondrogenesis in primary MSCs as evidenced by improved lacuna formation, proteoglycan and collagen type II staining, increased levels of GAG synthesis, and expression of mRNAs associated with chondrogenesis. Moreover, SOX9 modified aggregates showed a markedly lower tendency to progress towards hypertrophy, as judged by expression of the hypertrophy markers alkaline phosphatase, and collagen type X at the mRNA and protein levels. Conclusion Adenoviral SOX9 gene transfer induces chondrogenic differentiation of human primary MSCs in pellet culture more effectively than TGFB1 gene transfer with lower levels of chondrocyte hypertrophy after 3 weeks of in vitro culture. Such technology might enable the formation of more stable hyaline cartilage repair tissues in vivo. KW - Mesenchymal stem cell KW - Cartilage KW - SOX9 KW - Gene therapy KW - Chondrogenesis KW - Hypertrophy KW - Adenovirus KW - Bone marrow Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-229232 VL - 20 ER - TY - JOUR A1 - Tylek, Tina A1 - Blum, Carina A1 - Hrynevich, Andrei A1 - Schlegelmilch, Katrin A1 - Schilling, Tatjana A1 - Dalton, Paul D A1 - Groll, Jürgen T1 - Precisely defined fiber scaffolds with 40 μm porosity induce elongation driven M2-like polarization of human macrophages JF - Biofabrication N2 - Macrophages are key players of the innate immune system that can roughly be divided into the pro-inflammatory M1 type and the anti-inflammatory, pro-healing M2 type. While a transient initial pro-inflammatory state is helpful, a prolonged inflammation deteriorates a proper healing and subsequent regeneration. One promising strategy to drive macrophage polarization by biomaterials is precise control over biomaterial geometry. For regenerative approaches, it is of particular interest to identify geometrical parameters that direct human macrophage polarization. For this purpose, we advanced melt electrowriting (MEW) towards the fabrication of fibrous scaffolds with box-shaped pores and precise inter-fiber spacing from 100 μm down to only 40 μm. These scaffolds facilitate primary human macrophage elongation accompanied by differentiation towards the M2 type, which was most pronounced for the smallest pore size of 40 μm. These new findings can be important in helping to design new biomaterials with an enhanced positive impact on tissue regeneration. KW - cell elongation KW - human macrophages KW - melt electrowriting (MEW) KW - macrophage polarization KW - 3D scaffolds Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-254012 VL - 12 IS - 2 ER - TY - JOUR A1 - Sun, Wei A1 - Starly, Binil A1 - Daly, Andrew C A1 - Burdick, Jason A A1 - Groll, Jürgen A1 - Skeldon, Gregor A1 - Shu, Wenmiao A1 - Sakai, Yasuyuki A1 - Shinohara, Marie A1 - Nishikawa, Masaki A1 - Jang, Jinah A1 - Cho, Dong-Woo A1 - Nie, Minghao A1 - Takeuchi, Shoji A1 - Ostrovidov, Serge A1 - Khademhosseini, Ali A1 - Kamm, Roger D A1 - Mironov, Vladimir A1 - Moroni, Lorenzo A1 - Ozbolat, Ibrahim T T1 - The bioprinting roadmap JF - Biofabrication N2 - This bioprinting roadmap features salient advances in selected applications of the technique and highlights the status of current developments and challenges, as well as envisioned advances in science and technology, to address the challenges to the young and evolving technique. The topics covered in this roadmap encompass the broad spectrum of bioprinting; from cell expansion and novel bioink development to cell/stem cell printing, from organoid-based tissue organization to bioprinting of human-scale tissue structures, and from building cell/tissue/organ-on-a-chip to biomanufacturing of multicellular engineered living systems. The emerging application of printing-in-space and an overview of bioprinting technologies are also included in this roadmap. Due to the rapid pace of methodological advancements in bioprinting techniques and wide-ranging applications, the direction in which the field should advance is not immediately clear. This bioprinting roadmap addresses this unmet need by providing a comprehensive summary and recommendations useful to experienced researchers and newcomers to the field. KW - biofabrication KW - bioprinting KW - cell printing KW - biological models KW - disease models KW - organoids KW - organ-on-a-chip Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-254027 VL - 12 IS - 2 ER - TY - JOUR A1 - Wolf-Brandstetter, C A1 - Beutner, R A1 - Hess, R A1 - Bierbaum, S A1 - Wagner, K A1 - Scharnweber, D A1 - Gbureck, U A1 - Moseke, C T1 - Multifunctional calcium phosphate based coatings on titanium implants with integrated trace elements JF - Biomedical Materials N2 - For decades, the main focus of titanium implants developed to restore bone functionality was on improved osseointegration. Additional antimicrobial properties have now become desirable, due to the risk that rising antibiotic resistance poses for implant-associated infections. To this end, the trace elements of copper and zinc were integrated into calcium phosphate based coatings by electrochemically assisted deposition. In addition to their antimicrobial activity, zinc is reported to attract bone progenitor cells through chemotaxis and thus increase osteogenic differentiation, and copper to stimulate angiogenesis. Quantities of up to 68.9 ± 0.1 μg cm\(^{-2}\) of copper and 56.6 ± 0.4 μg cm\(^{-2}\) of zinc were deposited; co-deposition of both ions did not influence the amount of zinc but slightly increased the amount of copper in the coatings. The release of deposited copper and zinc species was negligible in serum-free simulated body fluid. In protein-containing solutions, a burst release of up to 10 μg ml\(^{-1}\) was observed for copper, while zinc was released continuously for up to 14 days. The presence of zinc was beneficial for adhesion and growth of human mesenchymal stromal cells in a concentration-dependent manner, but cytotoxic effects were already visible for coatings with an intermediate copper content. However, co-deposited zinc could somewhat alleviate the adverse effects of copper. Antimicrobial tests with E. coli revealed a decrease in adherent bacteria on brushite without copper or zinc of 60%, but if the coating contained both ions there was almost no bacterial adhesion after 12 h. Coatings with high zinc content and intermediate copper content had the overall best multifunctional properties. KW - coating KW - titanium KW - implant KW - pro-angiogenic KW - osteogenic KW - antimicrobial Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-254085 VL - 15 IS - 2 ER - TY - JOUR A1 - Weinreich, Oliver T1 - Psalterien in Würzburger Brevieren zwischen 1479 und 1575 JF - Würzburger Diözesangeschichtsblätter N2 - Es werden Psalterien aus Brevieren vorgestellt, die zwischen 1479 und 1575 in Würzburg oder im Auftrag des Fürstbischofs von Würzburg gedruckt worden sind. KW - Würzburg KW - Stundengebet KW - Würzburg KW - Brevier KW - Bibel KW - Geschichte 1479-1575 Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-303750 SN - 0342-3093 VL - 83 ER - TY - JOUR A1 - Bergengruen, Maximilian T1 - Wiederlesen, Korrigieren, Annotieren. Zum Verhältnis von Neuauflage und Fortsetzung bei Moscherosch, Grimmelshausen, Beer und Reuter JF - Simpliciana N2 - No abstract available. KW - Korrektur KW - Neuauflage KW - Reuter, Christian / Schelmuffsky KW - Beer, Johann / Der symplicianische Welt-Kucker oder abentheuerliche Jan Rebhu KW - Grimmelshausen, Hans Jakob Christoffel von / Continuatio des abentheurlichen Simplicissimi oder der Schluß desselben KW - Moscherosch, Johann Michael / Les Visiones de Don Francesco de Quevedo Villegas Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-303236 VL - 42 ER - TY - JOUR A1 - Hecht, Markus A1 - Leowanawat, Pawaret A1 - Gerlach, Tabea A1 - Stepanenko, Vladimir A1 - Stolte, Matthias A1 - Lehmann, Matthias A1 - Würthner, Frank T1 - Self‐Sorting Supramolecular Polymerization: Helical and Lamellar Aggregates of Tetra‐Bay‐Acyloxy Perylene Bisimide JF - Angewandte Chemie International Edition N2 - A new perylene bisimide (PBI), with a fluorescence quantum yield up to unity, self‐assembles into two polymorphic supramolecular polymers. This PBI bears four solubilizing acyloxy substituents at the bay positions and is unsubstituted at the imide position, thereby allowing hydrogen‐bond‐directed self‐assembly in nonpolar solvents. The formation of the polymorphs is controlled by the cooling rate of hot monomer solutions. They show distinctive absorption profiles and morphologies and can be isolated in different polymorphic liquid‐crystalline states. The interchromophoric arrangement causing the spectral features was elucidated, revealing the formation of columnar and lamellar phases, which are formed by either homo‐ or heterochiral self‐assembly, respectively, of the atropoenantiomeric PBIs. Kinetic studies reveal a narcissistic self‐sorting process upon fast cooling, and that the transformation into the heterochiral (racemic) sheetlike self‐assemblies proceeds by dissociation via the monomeric state. KW - liquid crystals KW - noncovalent interactions KW - self-assembly KW - structure elucidation KW - supramolecular chemistry Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-224586 VL - 59 IS - 39 SP - 17084 EP - 17090 ER - TY - JOUR A1 - Schlör, Daniel A1 - Ring, Markus A1 - Hotho, Andreas T1 - iNALU: Improved Neural Arithmetic Logic Unit JF - Frontiers in Artificial Intelligence N2 - Neural networks have to capture mathematical relationships in order to learn various tasks. They approximate these relations implicitly and therefore often do not generalize well. The recently proposed Neural Arithmetic Logic Unit (NALU) is a novel neural architecture which is able to explicitly represent the mathematical relationships by the units of the network to learn operations such as summation, subtraction or multiplication. Although NALUs have been shown to perform well on various downstream tasks, an in-depth analysis reveals practical shortcomings by design, such as the inability to multiply or divide negative input values or training stability issues for deeper networks. We address these issues and propose an improved model architecture. We evaluate our model empirically in various settings from learning basic arithmetic operations to more complex functions. Our experiments indicate that our model solves stability issues and outperforms the original NALU model in means of arithmetic precision and convergence. KW - neural networks KW - machine learning KW - arithmetic calculations KW - neural architecture KW - experimental evaluation Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-212301 SN - 2624-8212 VL - 3 ER - TY - JOUR A1 - Krauss, Jochen A1 - Vikuk, Veronika A1 - Young, Carolyn A. A1 - Krischke, Markus A1 - Mueller, Martin J. A1 - Baerenfaller, Katja T1 - Epichloë endophyte infection rates and alkaloid content in commercially available grass seed mixtures in Europe JF - Microorganisms N2 - Fungal endophytes of the genus Epichloë live symbiotically in cool season grass species and can produce alkaloids toxic to insects and vertebrates, yet reports of intoxication of grazing animals have been rare in Europe in contrast to overseas. However, due to the beneficial resistance traits observed in Epichloë infected grasses, the inclusion of Epichloë in seed mixtures might become increasingly advantageous. Despite the toxicity of fungal alkaloids, European seed mixtures are rarely tested for Epichloë infection and their infection status is unknown for consumers. In this study, we tested 24 commercially available seed mixtures for their infection rates with Epichloë endophytes and measured the concentrations of the alkaloids ergovaline, lolitrem B, paxilline, and peramine. We detected Epichloë infections in six seed mixtures, and four contained vertebrate and insect toxic alkaloids typical for Epichloë festucae var. lolii infecting Lolium perenne. As Epichloë infected seed mixtures can harm livestock, when infected grasses become dominant in the seeded grasslands, we recommend seed producers to test and communicate Epichloë infection status or avoiding Epichloë infected seed mixtures. KW - Epichloë spp. KW - grass endophytes KW - cool-season grass species KW - infection rates KW - alkaloids KW - toxicity KW - livestock KW - horses KW - Lolium perenne KW - perennial ryegrass Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-203323 SN - 2076-2607 VL - 8 IS - 4 ER - TY - JOUR A1 - Thorn, Simon A1 - Chao, Anne A1 - Georgiev, Konstadin B. A1 - Müller, Jörg A1 - Bässler, Claus A1 - Campbell, John L. A1 - Jorge, Castro A1 - Chen, Yan-Han A1 - Choi, Chang-Yong A1 - Cobb, Tyler P. A1 - Donato, Daniel C. A1 - Durska, Ewa A1 - Macdonald, Ellen A1 - Feldhaar, Heike A1 - Fontaine, Jospeh B. A1 - Fornwalt, Paula J. A1 - Hernández Hernández, Raquel María A1 - Hutto, Richard L. A1 - Koivula, Matti A1 - Lee, Eun-Jae A1 - Lindenmayer, David A1 - Mikusinski, Grzegorz A1 - Obrist, Martin K. A1 - Perlík, Michal A1 - Rost, Josep A1 - Waldron, Kaysandra A1 - Wermelinger, Beat A1 - Weiß, Ingmar A1 - Zmihorski, Michal A1 - Leverkus, Alexandro B. T1 - Estimating retention benchmarks for salvage logging to protect biodiversity JF - Nature Communications N2 - Forests are increasingly affected by natural disturbances. Subsequent salvage logging, a widespread management practice conducted predominantly to recover economic capital, produces further disturbance and impacts biodiversity worldwide. Hence, naturally disturbed forests are among the most threatened habitats in the world, with consequences for their associated biodiversity. However, there are no evidence-based benchmarks for the proportion of area of naturally disturbed forests to be excluded from salvage logging to conserve biodiversity. We apply a mixed rarefaction/extrapolation approach to a global multi-taxa dataset from disturbed forests, including birds, plants, insects and fungi, to close this gap. We find that 757% (mean +/- SD) of a naturally disturbed area of a forest needs to be left unlogged to maintain 90% richness of its unique species, whereas retaining 50% of a naturally disturbed forest unlogged maintains 73 +/- 12% of its unique species richness. These values do not change with the time elapsed since disturbance but vary considerably among taxonomic groups. Salvage logging has become a common practice to gain economic returns from naturally disturbed forests, but it could have considerable negative effects on biodiversity. Here the authors use a recently developed statistical method to estimate that ca. 75% of the naturally disturbed forest should be left unlogged to maintain 90% of the species unique to the area. KW - natural disturbance KW - bird communities KW - forest KW - management KW - beetle KW - conservation KW - windthrow KW - diversity KW - impact KW - fire Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-230512 VL - 11 ER - TY - JOUR A1 - Walter, Steffen A1 - Gruss, Sascha A1 - Neidlinger, Jana A1 - Stross, Isabelle A1 - Hann, Alexander A1 - Wagner, Martin A1 - Seufferlein, Thomas A1 - Walter, Benjamin T1 - Evaluation of an Objective Measurement Tool for Stress Level Reduction by Individually Chosen Music During Colonoscopy—Results From the Study “ColoRelaxTone” JF - Frontiers in Medicine N2 - Background and Aims: Colonoscopy as standard procedure in endoscopy is often perceived as uncomfortable for patients. Patient's anxiety is therefore a significant issue, which often lead to avoidance of participation of relevant examinations as CRC-screening. Non-pharmacological anxiety management interventions such as music might contribute to relaxation in the phase prior and during endoscopy. Although music's anxiolytic effects have been reported previously, no objective measurement of stress level reduction has been reported yet. Focus of this study was to evaluate the objective measurement of the state of relaxation in patients undergoing colonoscopy. Methods: Prospective study (n = 196) performed at one endoscopic high-volume center. Standard colonoscopy was performed in control group. Interventional group received additionally self-chosen music over earphones. Facial Electromyography (fEMG) activity was obtained. Clinician Satisfaction with Sedation Instrument (CSSI) and Patients Satisfaction with Sedation Instrument (PSSI) was answered by colonoscopists and patients, respectively. Overall satisfaction with music accompanied colonoscopy was obtained if applicable. Results: Mean difference measured by fEMG via musculus zygomaticus major indicated a significantly lower stress level in the music group [7.700(±5.560) μV vs. 4.820(±3.330) μV; p = 0.001]. Clinician satisfaction was significantly higher with patients listening to music [82.69(±15.04) vs. 87.3(±15.02) pts.; p = 0.001]. Patient's satisfaction was higher but did not differ significantly. Conclusions: We conclude that self-chosen music contributes objectively to a reduced stress level for patients and therefore subjectively perceived satisfaction for endoscopists. Therefore, music should be considered as a non-pharmacological treatment method of distress reduction especially in the beginning of endoscopic procedures. KW - colonoscopy KW - anxiety KW - stress level KW - music KW - relaxation Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-212337 VL - 7 ER - TY - JOUR A1 - Scharf, Benedikt A1 - Braggio, Alessandro A1 - Stambini, Elia A1 - Giazotto, Francesco A1 - Hankiewicz, Ewelina M. T1 - Topological Josephson heat engine JF - Communications Physics N2 - Topological superconductors represent a fruitful playing ground for fundamental research as well as for potential applications in fault-tolerant quantum computing. Especially Josephson junctions based on topological superconductors remain intensely studied, both theoretically and experimentally. The characteristic property of these junctions is their 4-periodic ground-state fermion parity in the superconducting phase difference. Using such topological Josephson junctions, we introduce the concept of a topological Josephson heat engine. We discuss how this engine can be implemented as a Josephson-Stirling cycle in topological superconductors, thereby illustrating the potential of the intriguing and fruitful marriage between topology and coherent thermodynamics. It is shown that the Josephson-Stirling cycle constitutes a highly versatile thermodynamic machine with different modes of operation controlled by the cycle temperatures. Finally, the thermodynamic cycle reflects the hallmark 4 pi -periodicity of topological Josephson junctions and could therefore be envisioned as a complementary approach to test topological superconductivity. Topological superconductors are expected to be a key component of quantum computing systems but reliably detecting their exotic properties is a challenge. Here, the authors propose a topological Josephson heat engine which uses thermodynamic effects to probe the 4 pi -periodic ground state of a topological superconductor. KW - superconductivity Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-230603 VL - 3 ER - TY - JOUR A1 - Balkenhol, Johannes A1 - Kaltdorf, Kristin V. A1 - Mammadova-Bach, Elmina A1 - Braun, Attila A1 - Nieswandt, Bernhard A1 - Dittrich, Marcus A1 - Dandekar, Thomas T1 - Comparison of the central human and mouse platelet signaling cascade by systems biological analysis JF - BMC Genomics N2 - Background Understanding the molecular mechanisms of platelet activation and aggregation is of high interest for basic and clinical hemostasis and thrombosis research. The central platelet protein interaction network is involved in major responses to exogenous factors. This is defined by systemsbiological pathway analysis as the central regulating signaling cascade of platelets (CC). Results The CC is systematically compared here between mouse and human and major differences were found. Genetic differences were analysed comparing orthologous human and mouse genes. We next analyzed different expression levels of mRNAs. Considering 4 mouse and 7 human high-quality proteome data sets, we identified then those major mRNA expression differences (81%) which were supported by proteome data. CC is conserved regarding genetic completeness, but we observed major differences in mRNA and protein levels between both species. Looking at central interactors, human PLCB2, MMP9, BDNF, ITPR3 and SLC25A6 (always Entrez notation) show absence in all murine datasets. CC interactors GNG12, PRKCE and ADCY9 occur only in mice. Looking at the common proteins, TLN1, CALM3, PRKCB, APP, SOD2 and TIMP1 are higher abundant in human, whereas RASGRP2, ITGB2, MYL9, EIF4EBP1, ADAM17, ARRB2, CD9 and ZYX are higher abundant in mouse. Pivotal kinase SRC shows different regulation on mRNA and protein level as well as ADP receptor P2RY12. Conclusions Our results highlight species-specific differences in platelet signaling and points of specific fine-tuning in human platelets as well as murine-specific signaling differences. KW - interspecies comparison KW - transcriptome KW - proteome KW - platelet KW - network KW - signaling KW - mouse KW - human KW - interactome KW - cascade Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-230377 VL - 21 ER - TY - JOUR A1 - Schlegel, Jan A1 - Sauer, Markus T1 - Hochaufgelöste Visualisierung einzelner Moleküle auf ganzen Zellen JF - BIOspektrum N2 - Biological systems are dynamic and three-dimensional but many techniques allow only static and two-dimensional observation of cells. We used three-dimensional (3D) lattice light-sheet single-molecule localization microscopy (dSTORM) to investigate the complex interactions and distribution of single molecules in the plasma membrane of whole cells. Different receptor densities of the adhesion receptor CD56 at different parts of the cell highlight the importance and need of three-dimensional observation and analysis techniques. KW - Visualisierung KW - Moleküle KW - Zellen Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-232365 SN - 0947-0867 VL - 7 ER - TY - JOUR A1 - Li, Ningbo A1 - Guan, Lianwu A1 - Gao, Yanbin A1 - Du, Shitong A1 - Wu, Menghao A1 - Guang, Xingxing A1 - Cong, Xiaodan T1 - Indoor and outdoor low-cost seamless integrated navigation system based on the integration of INS/GNSS/LIDAR system JF - Remote Sensing N2 - Global Navigation Satellite System (GNSS) provides accurate positioning data for vehicular navigation in open outdoor environment. In an indoor environment, Light Detection and Ranging (LIDAR) Simultaneous Localization and Mapping (SLAM) establishes a two-dimensional map and provides positioning data. However, LIDAR can only provide relative positioning data and it cannot directly provide the latitude and longitude of the current position. As a consequence, GNSS/Inertial Navigation System (INS) integrated navigation could be employed in outdoors, while the indoors part makes use of INS/LIDAR integrated navigation and the corresponding switching navigation will make the indoor and outdoor positioning consistent. In addition, when the vehicle enters the garage, the GNSS signal will be blurred for a while and then disappeared. Ambiguous GNSS satellite signals will lead to the continuous distortion or overall drift of the positioning trajectory in the indoor condition. Therefore, an INS/LIDAR seamless integrated navigation algorithm and a switching algorithm based on vehicle navigation system are designed. According to the experimental data, the positioning accuracy of the INS/LIDAR navigation algorithm in the simulated environmental experiment is 50% higher than that of the Dead Reckoning (DR) algorithm. Besides, the switching algorithm developed based on the INS/LIDAR integrated navigation algorithm can achieve 80% success rate in navigation mode switching. KW - vehicular navigation KW - GNSS/INS integrated navigation KW - INS/LIDAR integrated navigation KW - switching navigation Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-216229 SN - 2072-4292 VL - 12 IS - 19 ER - TY - JOUR A1 - Fofanov, Mikhail V. A1 - Prokopov, Dmitry Yu. A1 - Kuhl, Heiner A1 - Schartl, Manfred A1 - Trifonov, Vladimir A. T1 - Evolution of microRNA biogenesis genes in the sterlet (Acipenser ruthenus) and other polyploid vertebrates JF - International Journal of Molecular Sciences N2 - MicroRNAs play a crucial role in eukaryotic gene regulation. For a long time, only little was known about microRNA-based gene regulatory mechanisms in polyploid animal genomes due to difficulties of polyploid genome assembly. However, in recent years, several polyploid genomes of fish, amphibian, and even invertebrate species have been sequenced and assembled. Here we investigated several key microRNA-associated genes in the recently sequenced sterlet (Acipenser ruthenus) genome, whose lineage has undergone a whole genome duplication around 180 MYA. We show that two paralogs of drosha, dgcr8, xpo1, and xpo5 as well as most ago genes have been retained after the acipenserid-specific whole genome duplication, while ago1 and ago3 genes have lost one paralog. While most diploid vertebrates possess only a single copy of dicer1, we strikingly found four paralogs of this gene in the sterlet genome, derived from a tandem segmental duplication that occurred prior to the last whole genome duplication. ago1,3,4 and exportins1,5 look to be prone to additional segment duplications producing up to four-five paralog copies in ray-finned fishes. We demonstrate for the first time exon microsatellite amplification in the acipenserid drosha2 gene, resulting in a highly variable protein product, which may indicate sub- or neofunctionalization. Paralogous copies of most microRNA metabolism genes exhibit different expression profiles in various tissues and remain functional despite the rediploidization process. Subfunctionalization of microRNA processing gene paralogs may be beneficial for different pathways of microRNA metabolism. Genetic variability of microRNA processing genes may represent a substrate for natural selection, and, by increasing genetic plasticity, could facilitate adaptations to changing environments. KW - sturgeon KW - whole genome duplication KW - microRNA KW - gene duplications Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-285230 SN - 1422-0067 VL - 21 IS - 24 ER - TY - JOUR A1 - Naseem, Muhammad A1 - Osmanoğlu, Özge A1 - Kaltdorf, Martin A1 - Alblooshi, Afnan Ali M. A. A1 - Iqbal, Jibran A1 - Howari, Fares M. A1 - Srivastava, Mugdha A1 - Dandekar, Thomas T1 - Integrated framework of the immune-defense transcriptional signatures in the Arabidopsis shoot apical meristem JF - International Journal of Molecular Sciences N2 - The growing tips of plants grow sterile; therefore, disease-free plants can be generated from them. How plants safeguard growing apices from pathogen infection is still a mystery. The shoot apical meristem (SAM) is one of the three stem cells niches that give rise to the above ground plant organs. This is very well explored; however, how signaling networks orchestrate immune responses against pathogen infections in the SAM remains unclear. To reconstruct a transcriptional framework of the differentially expressed genes (DEGs) pertaining to various SAM cellular populations, we acquired large-scale transcriptome datasets from the public repository Gene Expression Omnibus (GEO). We identify here distinct sets of genes for various SAM cellular populations that are enriched in immune functions, such as immune defense, pathogen infection, biotic stress, and response to salicylic acid and jasmonic acid and their biosynthetic pathways in the SAM. We further linked those immune genes to their respective proteins and identify interactions among them by mapping a transcriptome-guided SAM-interactome. Furthermore, we compared stem-cells regulated transcriptome with innate immune responses in plants showing transcriptional separation among their DEGs in Arabidopsis. Besides unleashing a repertoire of immune-related genes in the SAM, our analysis provides a SAM-interactome that will help the community in designing functional experiments to study the specific defense dynamics of the SAM-cellular populations. Moreover, our study promotes the essence of large-scale omics data re-analysis, allowing a fresh look at the SAM-cellular transcriptome repurposing data-sets for new questions. KW - defense signaling KW - shoot apical meristem KW - CLV3p KW - meta-transcriptome KW - system inference KW - stem-cell-triggered immunity Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-285730 SN - 1422-0067 VL - 21 IS - 16 ER - TY - JOUR A1 - Doll, Julia A1 - Kolb, Susanne A1 - Schnapp, Linda A1 - Rad, Aboulfazl A1 - Rüschendorf, Franz A1 - Khan, Imran A1 - Adli, Abolfazl A1 - Hasanzadeh, Atefeh A1 - Liedtke, Daniel A1 - Knaup, Sabine A1 - Hofrichter, Michaela AH A1 - Müller, Tobias A1 - Dittrich, Marcus A1 - Kong, Il-Keun A1 - Kim, Hyung-Goo A1 - Haaf, Thomas A1 - Vona, Barbara T1 - Novel loss-of-function variants in CDC14A are associated with recessive sensorineural hearing loss in Iranian and Pakistani patients JF - International Journal of Molecular Sciences N2 - CDC14A encodes the Cell Division Cycle 14A protein and has been associated with autosomal recessive non-syndromic hearing loss (DFNB32), as well as hearing impairment and infertile male syndrome (HIIMS) since 2016. To date, only nine variants have been associated in patients whose initial symptoms included moderate-to-profound hearing impairment. Exome analysis of Iranian and Pakistani probands who both showed bilateral, sensorineural hearing loss revealed a novel splice site variant (c.1421+2T>C, p.?) that disrupts the splice donor site and a novel frameshift variant (c.1041dup, p.Ser348Glnfs*2) in the gene CDC14A, respectively. To evaluate the pathogenicity of both loss-of-function variants, we analyzed the effects of both variants on the RNA-level. The splice variant was characterized using a minigene assay. Altered expression levels due to the c.1041dup variant were assessed using RT-qPCR. In summary, cDNA analysis confirmed that the c.1421+2T>C variant activates a cryptic splice site, resulting in a truncated transcript (c.1414_1421del, p.Val472Leufs*20) and the c.1041dup variant results in a defective transcript that is likely degraded by nonsense-mediated mRNA decay. The present study functionally characterizes two variants and provides further confirmatory evidence that CDC14A is associated with a rare form of hereditary hearing loss. KW - CDC14A KW - DFNB32 KW - autosomal recessive hearing loss KW - exome sequencing KW - splicing KW - frameshift KW - non-sense mediated mRNA decay Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-285142 SN - 1422-0067 VL - 21 IS - 1 ER - TY - JOUR A1 - Stojanović, Stevan D. A1 - Fuchs, Maximilian A1 - Fiedler, Jan A1 - Xiao, Ke A1 - Meinecke, Anna A1 - Just, Annette A1 - Pich, Andreas A1 - Thum, Thomas A1 - Kunz, Meik T1 - Comprehensive bioinformatics identifies key microRNA players in ATG7-deficient lung fibroblasts JF - International Journal of Molecular Sciences N2 - Background: Deficient autophagy has been recently implicated as a driver of pulmonary fibrosis, yet bioinformatics approaches to study this cellular process are lacking. Autophagy-related 5 and 7 (ATG5/ATG7) are critical elements of macro-autophagy. However, an alternative ATG5/ATG7-independent macro-autophagy pathway was recently discovered, its regulation being unknown. Using a bioinformatics proteome profiling analysis of ATG7-deficient human fibroblasts, we aimed to identify key microRNA (miR) regulators in autophagy. Method: We have generated ATG7-knockout MRC-5 fibroblasts and performed mass spectrometry to generate a large-scale proteomics dataset. We further quantified the interactions between various proteins combining bioinformatics molecular network reconstruction and functional enrichment analysis. The predicted key regulatory miRs were validated via quantitative polymerase chain reaction. Results: The functional enrichment analysis of the 26 deregulated proteins showed decreased cellular trafficking, increased mitophagy and senescence as the major overarching processes in ATG7-deficient lung fibroblasts. The 26 proteins reconstitute a protein interactome of 46 nodes and miR-regulated interactome of 834 nodes. The miR network shows three functional cluster modules around miR-16-5p, miR-17-5p and let-7a-5p related to multiple deregulated proteins. Confirming these results in a biological setting, serially passaged wild-type and autophagy-deficient fibroblasts displayed senescence-dependent expression profiles of miR-16-5p and miR-17-5p. Conclusions: We have developed a bioinformatics proteome profiling approach that successfully identifies biologically relevant miR regulators from a proteomics dataset of the ATG-7-deficient milieu in lung fibroblasts, and thus may be used to elucidate key molecular players in complex fibrotic pathological processes. The approach is not limited to a specific cell-type and disease, thus highlighting its high relevance in proteome and non-coding RNA research. KW - bioinformatics KW - miR KW - proteomics KW - functional network analysis KW - senescence KW - lung fibrosis KW - autophagy Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-285181 SN - 1422-0067 VL - 21 IS - 11 ER - TY - JOUR A1 - Grimm, Oliver A1 - Weber, Heike A1 - Kittel-Schneider, Sarah A1 - Kranz, Thorsten M. A1 - Jacob, Christian P. A1 - Lesch, Klaus-Peter A1 - Reif, Andreas T1 - Impulsivity and Venturesomeness in an Adult ADHD Sample: Relation to Personality, Comorbidity, and Polygenic Risk JF - Frontiers in Psychiatry N2 - While impulsivity is a basic feature of attention-deficit/hyperactivity disorder (ADHD), no study explored the effect of different components of the Impulsiveness (Imp) and Venturesomeness (Vent) scale (IV7) on psychiatric comorbidities and an ADHD polygenic risk score (PRS). We used the IV7 self-report scale in an adult ADHD sample of 903 patients, 70% suffering from additional comorbid disorders, and in a subsample of 435 genotyped patients. Venturesomeness, unlike immediate Impulsivity, is not specific to ADHD. We consequently analyzed the influence of Imp and Vent also in the context of a PRS on psychiatric comorbidities of ADHD. Vent shows a distinctly different distribution of comorbidities, e.g., less anxiety and depression. PRS showed no effect on different ADHD comorbidities, but correlated with childhood hyperactivity. In a complementary analysis using principal component analysis with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition ADHD criteria, revised NEO Personality Inventory, Imp, Vent, and PRS, we identified three ADHD subtypes. These are an impulsive–neurotic type, an adventurous–hyperactive type with a stronger genetic component, and an anxious–inattentive type. Our study thus suggests the importance of adventurousness and the differential consideration of impulsivity in ADHD. The genetic risk is distributed differently between these subtypes, which underlines the importance of clinically motivated subtyping. Impulsivity subtyping might give insights into the organization of comorbid disorders in ADHD and different genetic background. KW - impulsivity KW - ADHD KW - polygenic risk score KW - venturesomeness KW - substance abuse disorder KW - attention KW - hyperactivity Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-219751 SN - 1664-0640 VL - 11 ER - TY - JOUR A1 - Oehler, Beatrice A1 - Kloka, Jan A1 - Mohammadi, Milad A1 - Ben-Kraiem, Adel A1 - Rittner, Heike L. T1 - D-4F, an ApoA-I mimetic peptide ameliorating TRPA1-mediated nocifensive behaviour in a model of neurogenic inflammation JF - Molecular Pain N2 - Background High doses of capsaicin are recommended for the treatment of neuropathic pain. However, low doses evoke mechanical hypersensitivity. Activation of the capsaicin chemosensor transient receptor potential vanilloid 1 (TRPV1) induces neurogenic inflammation. In addition to the release of pro-inflammatory mediators, reactive oxygen species are produced. These highly reactive molecules generate oxidised phospholipids and 4-hydroxynonenal (4-HNE) which then directly activate TRP ankyrin 1 (TRPA1). The apolipoprotein A-I mimetic peptide D-4F neutralises oxidised phospholipids. Here, we asked whether D-4F ameliorates neurogenic hypersensitivity in rodents by targeting reactive oxygen species and 4-HNE in the capsaicin-evoked pain model. Results Co-application of D-4F ameliorated capsaicin-induced mechanical hypersensitivity and allodynia as well as persistent heat hypersensitivity measured by Randell–Selitto, von Frey and Hargreaves test, respectively. In addition, mechanical hypersensitivity was blocked after co-injection of D-4F with the reactive oxygen species analogue H2O2 or 4-HNE. In vitro studies on dorsal root ganglion neurons and stably transfected cell lines revealed a TRPA1-dependent inhibition of the calcium influx when agonists were pre-incubated with D-4F. The capsaicin-induced calcium influx in TRPV1-expressing cell lines and dorsal root ganglion neurons sustained in the presence of D-4F. Conclusions D-4F is a promising compound to ameliorate TRPA1-dependent hypersensitivity during neurogenic inflammation. KW - TRPA1 KW - capsaicin KW - reactive oxygen species KW - oxidised lipids KW - pain KW - targeting Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-236061 VL - 16 ER - TY - JOUR A1 - Horvat, Sonja A1 - Vogel, Patrick A1 - Kampf, Thomas A1 - Brandl, Andreas A1 - Alshamsan, Aws A1 - Alhadlaq, Hisham A. A1 - Ahamed, Maqusood A1 - Albrecht, Krystyna A1 - Behr, Volker C. A1 - Beilhack, Andreas A1 - Groll, Jürgen T1 - Crosslinked Coating Improves the Signal‐to‐Noise Ratio of Iron Oxide Nanoparticles in Magnetic Particle Imaging (MPI) JF - ChemNanoMat N2 - Magnetic particle imaging is an emerging tomographic method used for evaluation of the spatial distribution of iron‐oxide nanoparticles. In this work, the effect of the polymer coating on the response of particles was studied. Particles with covalently crosslinked coating showed improved signal and image resolution. KW - crosslinked coating KW - imaging agents KW - magnetic properties KW - MPI KW - MPS Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-214718 VL - 6 IS - 5 SP - 755 EP - 758 ER - TY - JOUR A1 - Hesselbach, Hannah A1 - Seeger, Johannes A1 - Schilcher, Felix A1 - Ankenbrand, Markus A1 - Scheiner, Ricarda T1 - Chronic exposure to the pesticide flupyradifurone can lead to premature onset of foraging in honeybees Apis mellifera JF - Journal of Applied Ecology N2 - 1.Honeybees Apis mellifera and other pollinating insects suffer from pesticides in agricultural landscapes. Flupyradifurone is the active ingredient of a novel pesticide by the name of ‘Sivanto’, introduced by Bayer AG (Crop Science Division, Monheim am Rhein, Germany). It is recommended against sucking insects and marketed as ‘harmless’ to honeybees. Flupyradifurone binds to nicotinergic acetylcholine receptors like neonicotinoids, but it has a different mode of action. So far, little is known on how sublethal flupyradifurone doses affect honeybees. 2. We chronically applied a sublethal and field‐realistic concentration of flupyradifurone to test for long‐term effects on flight behaviour using radio‐frequency identification. We examined haematoxylin/eosin‐stained brains of flupyradifurone‐treated bees to investigate possible changes in brain morphology and brain damage. 3. A field‐realistic flupyradifurone dose of approximately 1.0 μg/bee/day significantly increased mortality. Pesticide‐treated bees initiated foraging earlier than control bees. No morphological damage in the brain was observed. 4. Synthesis and applications. The early onset of foraging induced by a chronical application of flupyradifurone could be disadvantageous for honeybee colonies, reducing the period of in‐hive tasks and life expectancy of individuals. Radio‐frequency identification technology is a valuable tool for studying pesticide effects on lifetime foraging behaviour of insects. KW - radiofrequency identification KW - flight behaviour KW - flupyradifurone KW - foraging KW - histology KW - honeybee KW - insecticide KW - mortality Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-212769 VL - 57 IS - 3 ER - TY - JOUR A1 - Esser, Peter A1 - Mehnert‐Theuerkauf, Anja A1 - Friedrich, Michael A1 - Johansen, Christoffer A1 - Brähler, Elmar A1 - Faller, Hermann A1 - Härter, Martin A1 - Koch, Uwe A1 - Schulz, Holger A1 - Wegscheider, Karl A1 - Weis, Joachim A1 - Kuba, Katharina A1 - Hinz, Andreas A1 - Hartung, Tim T1 - Risk and associated factors of depression and anxiety in men with prostate cancer: Results from a German multicenter study JF - Psycho‐Oncology N2 - Objective In order to optimize psycho‐oncological care, studies that quantify the extent of distress and identify certain risk groups are needed. Among patients with prostate cancer (PCa), findings on depression and anxiety are limited. Methods We analyzed data of PCa patients selected from a German multi‐center study. Depression and anxiety were assessed with the PHQ‐9 and the GAD‐7 (cut‐off ≥7). We provided physical symptom burden, calculated absolute and relative risk (AR and RR) of depression and anxiety across patient subsets and between patients and the general population (GP) and tested age as a moderator within the relationship of disease‐specific symptoms with depression and anxiety. Results Among 636 participants, the majority reported disease‐specific problems (sexuality: 60%; urination: 52%). AR for depression and anxiety was 23% and 22%, respectively. Significant RR were small, with higher risks of distress in patients who are younger (eg, RR\(_{depression}\) = 1.15; 95%‐CI: 1.06‐1.26), treated with chemotherapy (RR\(_{depression}\)n = 1.46; 95%‐CI: 1.09‐1.96) or having metastases (RR\(_{depression}\) = 1.30; 95%‐CI: 1.02‐1.65). Risk of distress was slightly elevated compared to GP (eg, RR\(_{depression}\) = 1.13; 95%‐CI: 1.07‐1.19). Age moderated the relationship between symptoms and anxiety (B\(_{urination}\) = −0.10, P = .02; B\(_{sexuality}\) = −0.11, P = .01). Conclusions Younger patients, those with metastases or treatment with chemotherapy seem to be at elevated risk for distress and should be closely monitored. Many patients suffer from disease‐specific symptom burden, by which younger patients seem to be particularly distressed. Support of coping mechanisms associated with disease‐specific symptom burden seems warranted. KW - anxiety KW - cancer KW - depression KW - oncology KW - prostatic neoplasms Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-218277 VL - 29 IS - 10 SP - 1604 EP - 1612 ER - TY - JOUR A1 - Mühlberg, Eric A1 - Umstätter, Florian A1 - Domhan, Cornelius A1 - Hertlein, Tobias A1 - Ohlsen, Knut A1 - Krause, Andreas A1 - Kleist, Christian A1 - Beijer, Barbro A1 - Zimmermann, Stefan A1 - Haberkorn, Uwe A1 - Mier, Walter A1 - Uhl, Philipp T1 - Vancomycin-lipopeptide conjugates with high antimicrobial activity on vancomycin-resistant enterococci JF - Pharmaceuticals N2 - Multidrug-resistant bacteria represent one of the most important health care problems worldwide. While there are numerous drugs available for standard therapy, there are only a few compounds capable of serving as a last resort for severe infections. Therefore, approaches to control multidrug-resistant bacteria must be implemented. Here, a strategy of reactivating the established glycopeptide antibiotic vancomycin by structural modification with polycationic peptides and subsequent fatty acid conjugation to overcome the resistance of multidrug-resistant bacteria was followed. This study especially focuses on the structure–activity relationship, depending on the modification site and fatty acid chain length. The synthesized conjugates showed high antimicrobial potential on vancomycin-resistant enterococci. We were able to demonstrate that the antimicrobial activity of the vancomycin-lipopeptide conjugates depends on the chain length of the attached fatty acid. All conjugates showed good cytocompatibility in vitro and in vivo. Radiolabeling enabled the in vivo determination of pharmacokinetics in Wistar rats by molecular imaging and biodistribution studies. An improved biodistribution profile in comparison to unmodified vancomycin was observed. While vancomycin is rapidly excreted by the kidneys, the most potent conjugate shows a hepatobiliary excretion profile. In conclusion, these results demonstrate the potential of the structural modification of already established antibiotics to provide highly active compounds for tackling multidrug-resistant bacteria. KW - antibiotics KW - multidrug-resistant bacteria KW - enterococci KW - vancomycin KW - structural modification KW - fatty acids KW - polycationic peptides Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-205879 SN - 1424-8247 VL - 13 IS - 6 ER - TY - JOUR A1 - Mainardi, Francesco A1 - Consiglio, Armando T1 - The Wright Functions of the Second Kind in Mathematical Physics JF - Mathematics N2 - In this review paper, we stress the importance of the higher transcendental Wright functions of the second kind in the framework of Mathematical Physics. We first start with the analytical properties of the classical Wright functions of which we distinguish two kinds. We then justify the relevance of the Wright functions of the second kind as fundamental solutions of the time-fractional diffusion-wave equations. Indeed, we think that this approach is the most accessible point of view for describing non-Gaussian stochastic processes and the transition from sub-diffusion processes to wave propagation. Through the sections of the text and suitable appendices, we plan to address the reader in this pathway towards the applications of the Wright functions of the second kind. KW - fractional calculus KW - Wright functions KW - Green’s functions KW - diffusion-wave equation KW - Laplace transform Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-207782 SN - 2227-7390 VL - 8 IS - 6 ER - TY - JOUR A1 - Verma, Shwetabh A1 - Kehrer, Tobias A1 - Hesser, Jürgen A1 - Arba Mosquera, Samuel T1 - Analysis of Impact of Humidity and Temperature on Excimer Laser Ablation of Polyethylene Terephthalate, Polymethylmethacrylate, and Porcine Corneal Tissue JF - Lasers in Surgery and Medicine N2 - Background and Objectives To analyze the impact of humidity and temperature on excimer laser ablation of polyethylene terephthalate (PET), polymethylmethacrylate (PMMA) and porcine corneal tissue, and an ablation model to compensate for the temperature and humidity changes on ablation efficiency. Study Design/Materials and Methods The study was conducted using an AMARIS 1050RS (Schwind eye‐tech‐solutions) placed inside a climate chamber at ACTS. Ablations were performed on PET, PMMA, and porcine cornea. The impact of a wide range of temperature (~18°C to ~30°C) and relative humidity (~25% to ~80%) on laser ablation outcomes was tested using nine climate test settings. For porcine eyes, change in defocus was calculated from the difference of post‐ablation to pre‐ablation average keratometry readings. Laser scanning deflectometry was performed to measure refractive change achieved in PMMA. Multiple linear regression was performed using the least square method with predictive factors: temperature, relative humidity, time stamp. Influence of climate settings was modeled for pulse energy, pulse fluence, ablation efficiency on PMMA and porcine cornea tissue. Results Temperature changes did not affect laser pulse energy, pulse fluence (PET), and ablation efficiency (on PMMA or porcine corneal tissue) significantly. Changes in relative humidity were critical and significantly affected laser pulse energy, high fluence and low fluence. The opposite trend was observed between the ablation performance on PMMA and porcine cornea. Conclusions The proposed well‐fitting multi‐linear model can be utilized for compensation of temperature and humidity changes on ablation efficiency. Based on this model, a working window for optimum operation has been found (temperature 18°C to 28°C and relative humidity 25% to 65%) for a maximum deviation of ±2.5% in ablation efficiency in PMMA and porcine corneal tissue. KW - impact of humidity and temperature KW - excimer laser ablation KW - PMMA KW - cornea KW - PET KW - refractive surgery Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-213395 VL - 52 IS - 7 SP - 627 EP - 638 ER - TY - JOUR A1 - Ewing, William C. A1 - Dellermann, Theresa A1 - Angel Wong, Y. T. A1 - Mattock, James D. A1 - Vargas, Alfredo A1 - Bryce, David L. A1 - Dewhurst, Rian D. A1 - Braunschweig, Holger T1 - \(\pi\)‐Complexes of Diborynes with Main Group Atoms JF - Chemistry – An Asian Journal N2 - We present herein an in‐depth study of complexes in which a molecule containing a boron‐boron triple bond is bound to tellurate cations. The analysis allows the description of these salts as true π complexes between the B−B triple bond and the tellurium center. These complexes thus extend the well‐known Dewar‐Chatt‐Duncanson model of bonding to compounds made up solely of p block elements. Structural, spectroscopic and computational evidence is offered to argue that a set of recently reported heterocycles consisting of phenyltellurium cations complexed to diborynes bear all the hallmarks of \(\pi\)‐complexes in the \(\pi\)‐complex/metallacycle continuum envisioned by Joseph Chatt. Described as such, these compounds are unique in representing the extreme of a metal‐free continuum with conventional unsaturated three‐membered rings (cyclopropenes, azirenes, borirenes) occupying the opposite end. KW - boron KW - main group elements KW - solid-state NMR KW - \(\pi\) interactions KW - multiple bonds Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-214677 VL - 15 IS - 10 SP - 1553 EP - 1557 ER - TY - JOUR A1 - Üçeyler, Nurcan A1 - Buchholz, Hans-Georg A1 - Kewenig, Susanne A1 - Ament, Stephan-Johann A1 - Birklein, Frank A1 - Schreckenberger, Mathias A1 - Sommer, Claudia T1 - Cortical Binding Potential of Opioid Receptors in Patients With Fibromyalgia Syndrome and Reduced Systemic Interleukin-4 Levels – A Pilot Study JF - Frontiers in Neuroscience N2 - Objective: We investigated cerebral opioid receptor binding potential in patients with fibromyalgia syndrome (FMS) using positron-emission-tomography (PET) and correlated our results with patients’ systemic interleukin-4 (IL-4) gene expression. Methods: In this pilot study, seven FMS patients (1 man, 6 women) agreed to participate in experimental PET scans. All patients underwent neurological examination, were investigated with questionnaires for pain, depression, and FMS symptoms. Additionally, blood for IL-4 gene expression analysis was withdrawn at two time points with a median latency of 1.3 years. Patients were investigated in a PET scanner using the opioid receptor ligand F-18-fluoro-ethyl-diprenorphine ([18F]FEDPN) and results were compared with laboratory normative values. Results: Neurological examination was normal in all FMS patients. Reduced opioid receptor binding was found in mid cingulate cortex compared to healthy controls (p < 0.005). Interestingly, three patients with high systemic IL-4 gene expression had increased opioid receptor binding in the fronto-basal cortex compared to those with low IL-4 gene expression (p < 0.005). Conclusion: Our data give further evidence for a reduction in cortical opioid receptor availability in FMS patients as another potential central nervous system contributor to pain in FMS. KW - fibromyalgia syndrome KW - PET KW - brain KW - opioid KW - IL-4 Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-204457 SN - 1662-453X VL - 14 ER - TY - JOUR A1 - Kauffmann, Frederic A1 - Höhne, Christian A1 - Assaf, Alexandre Thomas A1 - Vollkommer, Tobias A1 - Semmusch, Jan A1 - Reitmeier, Aline A1 - Stein, Jamal Michel A1 - Heiland, Max A1 - Smeets, Ralf A1 - Rutkowski, Rico T1 - The influence of local pamidronate application on alveolar dimensional preservation after tooth extraction — an animal experimental study JF - International Journal of Molecular Sciences N2 - The aim of this randomized, controlled animal exploratory trial was to investigate the influence of local application of aminobisphosphonate pamidronate during the socket preservation procedure. Mandibular premolars were extracted in five Göttingen minipigs. Two animals underwent socket preservation using BEGO OSS (n = 8 sockets) and three animals using BEGO OSS + Pamifos (15 mg) (n = 12 sockets). After jaw impression, cast models (baseline, eight weeks postoperative) were digitized using an inLab X5 scanner (Dentsply Sirona) and the generated STL data were superimposed and analyzed with GOM Inspect 2018 (GOM, Braunschweig). After 16 weeks, the lower jaws were prepared and examined using standard histological methods. In the test group (BEGO OSS + pamidronate), buccooral dimensional loss was significantly lower, both vestibulary (−0.80 ± 0.57 mm vs. −1.92 ± 0.63 mm; p = 0.00298) and lingually (−1.36 ± 0.58 mm vs. −2.56 ± 0.65 mm; p = 0.00104) compared with the control group (BEGO OSS). The test group showed a significant difference between vestibular and lingual dimensional loss (p = 0.04036). Histology showed cortical and cancellous bone in the alveolar sockets without signs of local inflammation. Adjuvant application of pamidronate during socket preservation reduces alveolar dimensional loss significantly. Further investigations with regard to dose–response relationships, volume effects, side effects, and a verification of the suitability in combination with other bone substitute materials (BSMs) are necessary. KW - pamidronate KW - socket preservation KW - ridge preservation KW - bone remodeling KW - bone regeneration KW - bisphosphonates Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-285173 SN - 1422-0067 VL - 21 IS - 10 ER - TY - JOUR A1 - Sajko, Sara A1 - Grishkovskaya, Irina A1 - Kostan, Julius A1 - Graewert, Melissa A1 - Setiawan, Kim A1 - Trübestein, Linda A1 - Niedermüller, Korbinian A1 - Gehin, Charlotte A1 - Sponga, Antonio A1 - Puchinger, Martin A1 - Gavin, Anne-Claude A1 - Leonard, Thomas A. A1 - Svergun, Dimitri I. A1 - Smith, Terry K. A1 - Morriswood, Brooke A1 - Djinovic-Carugo, Kristina T1 - Structures of three MORN repeat proteins and a re-evaluation of the proposed lipid-binding properties of MORN repeats JF - PLoS One N2 - MORN (Membrane Occupation and Recognition Nexus) repeat proteins have a wide taxonomic distribution, being found in both prokaryotes and eukaryotes. Despite this ubiquity, they remain poorly characterised at both a structural and a functional level compared to other common repeats. In functional terms, they are often assumed to be lipid-binding modules that mediate membrane targeting. We addressed this putative activity by focusing on a protein composed solely of MORN repeats-Trypanosoma brucei MORN1. Surprisingly, no evidence for binding to membranes or lipid vesicles by TbMORN1 could be obtained either in vivo or in vitro. Conversely, TbMORN1 did interact with individual phospholipids. High- and low-resolution structures of the MORN1 protein from Trypanosoma brucei and homologous proteins from the parasites Toxoplasma gondii and Plasmodium falciparum were obtained using a combination of macromolecular crystallography, small-angle X-ray scattering, and electron microscopy. This enabled a first structure-based definition of the MORN repeat itself. Furthermore, all three structures dimerised via their C-termini in an antiparallel configuration. The dimers could form extended or V-shaped quaternary structures depending on the presence of specific interface residues. This work provides a new perspective on MORN repeats, showing that they are protein-protein interaction modules capable of mediating both dimerisation and oligomerisation. KW - recognition nexus domain KW - trypanosoma brucei KW - blood stream KW - phosphatidylserine transport KW - biological macromolecules KW - membrane occupation KW - solution scattering KW - molecular cloning KW - flagellar pocket KW - endocytosis Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-231261 VL - 15 IS - 23 ER - TY - JOUR A1 - Flachenecker, Peter A1 - Bures, Anna Karoline A1 - Gawlik, Angeli A1 - Weiland, Ann-Christin A1 - Kuld, Sarah A1 - Gusowski, Klaus A1 - Streber, René A1 - Pfeifer, Klaus A1 - Tallner, Alexander T1 - Efficacy of an internet-based program to promote physical activity and exercise after inpatient rehabilitation in persons with multiple sclerosis: a randomized, single-blind, controlled study JF - International Journal of Environmental Research and Public Health N2 - Background: Multimodal rehabilitation improves fatigue and mobility in persons with multiple sclerosis (PwMS). Effects are transient and may be conserved by internet-based physical activity promotion programs. Objective: Evaluate the effects of internet-based physical activity and exercise promotion on fatigue, quality of life, and gait in PwMS after inpatient rehabilitation. Methods: PwMS (Expanded Disability Status Scale (EDSS) ≤ 6.0, fatigue: Würzburg Fatigue Inventory for Multiple Sclerosis (WEIMuS) ≥ 32) were randomized into an intervention group (IG) or a control group (CG). After rehabilitation, IG received 3 months of internet-based physical activity promotion, while CG received no intervention. Primary outcome: self-reported fatigue (WEIMuS). Secondary outcomes: quality of life (Multiple Sclerosis Impact Scale 29, MSIS-29), gait (2min/10m walking test, Tinetti score). Measurements: beginning (T0) and end (T1) of inpatient rehabilitation, 3 (T2) and 6 (T3) months afterwards. Results: 64 of 84 PwMS were analyzed (IG: 34, CG: 30). After rehabilitation, fatigue decreased in both groups. At T2 and T3, fatigue increased again in CG but was improved in IG (p < 0.001). MSIS-29 improved in both groups at T1 but remained improved at T2 and T3 only in IG. Gait improvements were more pronounced in IG at T2. Conclusions: The study provides Class II evidence that the effects of rehabilitation on fatigue, quality of life, and gait can be maintained for 3–6 months with an internet-based physical activity and exercise promotion program. KW - multiple sclerosis KW - rehabilitation KW - fatigue KW - quality of life KW - walking KW - physical activity KW - exercise KW - online systems KW - internet-based intervention KW - health behavior Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-207863 SN - 1660-4601 VL - 17 IS - 12 ER - TY - JOUR A1 - Ohlmann, Brigitte A1 - Waldecker, Moritz A1 - Leckel, Michael A1 - Bömicke, Wolfgang A1 - Behnisch, Rouven A1 - Rammelsberg, Peter A1 - Schmitter, Marc T1 - Correlations between sleep bruxism and temporomandibular disorders JF - Journal of Clinical Medicine N2 - The aim of this study was to identify correlations between sleep bruxism (SB) and temporomandibular disorders (TMD) as diagnosed by means of the research diagnostic criteria for temporomandibular disorders (RDC/TMD). Sleep bruxism was diagnosed on the basis of I) validated questionnaires, II) clinical symptoms, and III) electromyographic/electrocardiographic data. A total of 110 subjects were included in the study. Fifty-eight patients were identified as bruxers and 52 as nonbruxers. A psychosocial assessment was also performed. An RDC/TMD group-I diagnosis (myofascial pain) was made for 10 out of 58 bruxers, whereas none of the nonbruxers received a diagnosis of this type. No significant differences were found between bruxers and nonbruxers with regard to RDC/TMD group-II (disc displacement) and group-III (arthralgia, arthritis, arthrosis) diagnoses. Somatization was significantly more common among bruxers than nonbruxers. Multivariate logistic regression analysis revealed that somatization was the only factor significantly correlated with the diagnosis of myofascial pain. The results of this study indicate a correlation between myofascial pain, as diagnosed using the RDC/TMD, and somatization. It seems that somatization is a stronger predictor of an RDC/TMD diagnosis of myofascial pain than sleep bruxism is. KW - sleep bruxism KW - TMD KW - electromyographic/electrocardiographic data Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-200662 SN - 2077-0383 VL - 9 IS - 2 ER - TY - JOUR A1 - Kunz, Felix A1 - Kayserili, Hülya A1 - Midro, Alina A1 - de Silva, Deepthi A1 - Basnayake, Sriyani A1 - Güven, Yeliz A1 - Borys, Jan A1 - Schanze, Denny A1 - Stellzig‐Eisenhauer, Angelika A1 - Bloch‐Zupan, Agnes A1 - Zenker, Martin T1 - Characteristic dental pattern with hypodontia and short roots in Fraser syndrome JF - American Journal of Medical Genetics Part A N2 - Fraser syndrome (FS) is a rare autosomal recessive multiple congenital malformation syndrome characterized by cryptophthalmos, cutaneous syndactyly, renal agenesis, ambiguous genitalia, and laryngotracheal anomalies. It is caused by biallelic mutations of FRAS1, FREM2, and GRIP1 genes, encoding components of a protein complex that mediates embryonic epithelial–mesenchymal interactions. Anecdotal reports have described abnormal orodental findings in FS, but no study has as yet addressed the orodental findings of FS systematically. We reviewed dental radiographs of 10 unrelated patients with FS of different genetic etiologies. Dental anomalies were present in all patients with FS and included hypodontia, dental crowding, medial diastema, and retained teeth. A very consistent pattern of shortened dental roots of most permanent teeth as well as altered length/width ratio with shortened dental crowns of upper incisors was also identified. These findings suggest that the FRAS1–FREM complex mediates critical mesenchymal–epithelial interactions during dental crown and root development. The orodental findings of FS reported herein represent a previously underestimated manifestation of the disorder with significant impact on orodental health for affected individuals. Integration of dentists and orthodontists into the multidisciplinary team for management of FS is therefore recommended. KW - dental roots KW - Fraser syndrome KW - hypodontia KW - orodental health KW - taurodontism Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-216147 VL - 182 IS - 7 SP - 1681 EP - 1689 ER - TY - JOUR A1 - Höhne, Christian A1 - Schwarzbauer, Raphael A1 - Schmitter, Marc T1 - Introduction of a new teaching concept for crown preparation with 3D printed teeth JF - European Journal of Dental Education N2 - Introduction For both students and teachers, it is challenging to learn and teach a correct crown preparation. The purpose of this study was the design, feasibility and evaluation of a 3D printed tooth model with internal preparation for dental education in crown preparation and to analyse the quality of the prepared printed teeth in comparison with prepared standard model teeth. Materials and methods A printable tooth was designed and printed by a stereolithographic printer. 38 fourth‐year dental students in the first clinical course in prosthodontics were trained in a voluntary course using printed teeth. Different aspects of the printed tooth were evaluated by a questionnaire using German school grades (1 best to 5 worst). The quality of the preparation with the printed teeth and standard training teeth was also rated in an evaluation form done by an expert group consisting of five experienced dentists. Results The workflow was feasible and cost‐effective for the production of the teeth. The overall rating of the printed tooth was Ø 2.0 ± 0.34 in the questionnaire completed by the students. The students rated the printed tooth model (Ø 2.1 ± 0.85) as significantly better than the standard model tooth (Ø 3.3 ± 0.77; P = .000). The students reported great benefits in the use of this model tooth, for example valuable replacement of a standard model and real teeth, direct control of material loss. The quality of the preparation was evaluated by the expert group as significantly better with an overall mean grade of Ø 2.6 ± 0.37 for the printed teeth compared to Ø 2.9 ± 0.42 for the standard model teeth (P = .000). Conclusions The feasibility of this teaching concept was confirmed. The students favoured to work on the innovative 3D‐teeth with internal preparation, emphasising the usefulness of this technique in dental education. The expert group confirmed also the significant training effect of this tooth model in contrast to a standard model tooth. KW - 3D printing KW - additive manufacturing KW - clinical practice KW - dental education KW - printed tooth KW - student training Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-218133 VL - 24 IS - 3 SP - 526 EP - 534 ER - TY - JOUR A1 - Höhne, Christian A1 - Dickhaut, Nora A1 - Schmitter, Marc T1 - Introduction of a new teaching concept for dentin post preparation with 3D printed teeth JF - European Journal of Dental Education N2 - Introduction The preparation for dentin posts is difficult and hard to learn. There are currently no reproducible simulation models to train this clinical procedure. The purpose of this study was the design, feasibility and evaluation of a three‐dimensional (3D) printed tooth model for the pre‐clinical teaching of students. Materials and methods A printable tooth was designed and printed by a stereolithographic printer. A total of 48 fourth‐year dental students in the first clinical course in prosthodontics were trained in a voluntary hands‐on course on 4 similar printed teeth. The students used standard model teeth and real‐teeth models during their education. They had experience in caries removement and root canal treatment on real patients. Root perforations were counted for every attempt. The different benefits of the 3D printed tooth were evaluated by a questionnaire using German school grades from 1 (best) to 6 (worst). Results The overall rating of the printed tooth was Ø1.9 ± 0.3. The item “suitable exercise option” was rated Ø2.0 ± 0.8, and the teeth were “easy to use” Ø1.9 ± 0.9. The item “realistic approach to dentin post preparation” was rated Ø2.1 ± 0.8, and the teeth showed the “shortcomings at a root perforation” Ø1.5 ± 0.6. The students reported to have much more motivation and enthusiasm to improve their skills with the printed teeth Ø2.1 ± 0.9. They had a strong desire to include these teeth in their pre‐clinical education before the first patient treatment Ø1.6 ± 0.8. The success rate of the dentin post preparation was significantly better for the second 25% (P = .047) and fourth 48% (P = .04) attempt. Conclusions The feasibility of this teaching concept was confirmed. The students had the possibility to learn a correct dentin post preparation on a printed tooth model. The learning effect with this tooth model was rated as good to very good by the questionnaire. KW - 3D printing KW - additive manufacturing KW - CAD KW - CAM KW - clinical practice KW - dental education KW - dentin post KW - printed tooth KW - rapid prototyping KW - stereolithography KW - student training Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-215586 VL - 24 IS - 3 SP - 499 EP - 506 ER - TY - JOUR A1 - Thiess, Torsten A1 - Ernst, Moritz A1 - Kupfer, Thomas A1 - Braunschweig, Holger T1 - Facile Access to Substituted 1,4‐Diaza‐2,3‐Diborinines JF - Chemistry – A European Journal N2 - Several bis(dimethylamino)‐substituted 1,4‐diaza‐2,3‐diborinines (DADBs) were synthesized with variable substituents at the backbone nitrogen atoms. By reaction with HCl or BX\(_{3}\) (X=Br, I), these species were successfully converted into their synthetically more useful halide congeners. The high versatility of the generated B−X bonds in further functionalization reactions at the boron centers was demonstrated by means of salt elimination (MeLi) and commutation (NMe\(_{2}\) DADBs) reactions, thus making the DADB system a general structural motif in diborane(4) chemistry. A total of 18 DADB derivatives were characterized in the solid state by X‐ray diffraction, revealing a strong dependence of the heterocyclic bonding parameters from the exocyclic substitution pattern at boron. According to our experiments towards the realization of a Dipp‐substituted, sterically encumbered DADB, the mechanism of DADB formation proceeds via a transient four‐membered azadiboretidine intermediate that subsequently undergoes ring expansion to afford the six‐membered DADB heterocycle. KW - azadiboretidines KW - B,N-heterocycles KW - diazadiborinines KW - diboranes KW - ring expansion Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-214650 VL - 26 IS - 13 SP - 2967 EP - 2972 ER - TY - JOUR A1 - Sarma, Bhavishya A1 - Willmes, Christoph A1 - Angerer, Laura A1 - Adam, Christian A1 - Becker, Jürgen C. A1 - Kervarrec, Thibault A1 - Schrama, David A1 - Houben, Roland T1 - Artesunate affects T antigen expression and survival of virus-positive Merkel cell carcinoma JF - Cancers N2 - Merkel cell carcinoma (MCC) is a rare and highly aggressive skin cancer with frequent viral etiology. Indeed, in about 80% of cases, there is an association with Merkel cell polyomavirus (MCPyV); the expression of viral T antigens is crucial for growth of virus-positive tumor cells. Since artesunate — a drug used to treat malaria — has been reported to possess additional anti-tumor as well as anti-viral activity, we sought to evaluate pre-clinically the effect of artesunate on MCC. We found that artesunate repressed growth and survival of MCPyV-positive MCC cells in vitro. This effect was accompanied by reduced large T antigen (LT) expression. Notably, however, it was even more efficient than shRNA-mediated downregulation of LT expression. Interestingly, in one MCC cell line (WaGa), T antigen knockdown rendered cells less sensitive to artesunate, while for two other MCC cell lines, we could not substantiate such a relation. Mechanistically, artesunate predominantly induces ferroptosis in MCPyV-positive MCC cells since known ferroptosis-inhibitors like DFO, BAF-A1, Fer-1 and β-mercaptoethanol reduced artesunate-induced death. Finally, application of artesunate in xenotransplanted mice demonstrated that growth of established MCC tumors can be significantly suppressed in vivo. In conclusion, our results revealed a highly anti-proliferative effect of the approved and generally well-tolerated anti-malaria compound artesunate on MCPyV-positive MCC cells, suggesting its potential usage for MCC therapy. KW - artesunate KW - Merkel cell carcinoma KW - MCC KW - polyomavirus KW - ferroptosis Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-203851 SN - 2072-6694 VL - 12 IS - 4 ER - TY - JOUR A1 - Scheuermann, Manuela T1 - „Frauen, Frieden und Sicherheit“ unter den Bedingungen der COVID-19 Pandemie T1 - “Women, Peace and Security” under the conditions of COVID-19 pandemics JF - Zeitschrift für Friedens- und Konfliktforschung N2 - Die COVID-19 Pandemie und ihre gesamtgesellschaftlichen Folgen werden zum Stresstest für die globale Agenda „Frauen, Frieden und Sicherheit“. Mit dieser Agenda verfolgt die Weltgemeinschaft seit dem Jahr 2000 das Ziel, Frauen in Situationen von gewaltsamen Konflikten und in der Phase des Wiederaufbaus vor Gewalt und Menschenrechtsverletzungen zu schützen, ihnen eine belangvolle Partizipation im Friedensprozess zu ermöglichen und so zu einem gendersensiblen Friedensbildungsprozess beizutragen. Im vorliegenden Beitrag wird argumentiert, dass die Folgen der Corona-Krise einen Rückfall im Implementierungsprozess der Agenda auslösen könnten, insbesondere in Bezug auf Geschlechterstereotype. Es wird diskutiert ob bestimmte als traditionell-weiblich perzipierte Rollen verfestigt werden und welche Auswirkungen diese Beobachtung auf die Zukunft der globalen Agenda haben könnte. Von besonderer Bedeutung ist hierbei das Konzept der globalen Fürsorge. N2 - The COVID-19 pandemic and its consequences for society as a whole are becoming a stress test for the global agenda “Women, Peace and Security“. With this agenda, the international community has been pursuing since 2000 the goal of protecting women in situations of violent conflict and in the reconstruction phase from violence and human rights violations, enabling them to participate in the peace process in a meaningful way and thus contributing to a gender-sensitive peacebuilding process. The paper argues that the consequences of the Corona crisis could trigger a relapse in the implementation process of the Agenda, especially with regard to gender stereotypes. It is discussed whether certain roles perceived as traditional feminine are being consolidated and what effects this observation could have on the future of the global agenda. The concept of global care is of particular importance. KW - COVID-19 Pandemie KW - Geschlechterstereotype KW - Rollenbilder von Frauen KW - Feministische Friedensforschung KW - Partizipation von Frauen KW - Globale Fürsorge KW - gender stereotypes KW - female roles KW - feminist peace research KW - female participation KW - global care Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-235579 SN - 2192-1741 VL - 9 ER - TY - JOUR A1 - Kraft, Stephan T1 - "Gipp ammall BILD." Zur Initialzündung der Doppelhandlung in Arno Schmidts "Kaff auch Mare Crisium" JF - Bargfelder Bote N2 - Kein Abstract verfügbar. KW - Schmidt, Arno KW - Kaff auch Mare Crisium Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-282509 ER - TY - JOUR T1 - Search for squarks and gluinos in final states with same-sign leptons and jets using 139 fb\(^{-1}\) of data collected with the ATLAS detector JF - Journal of High Energy Physics N2 - A search for supersymmetric partners of gluons and quarks is presented, involving signatures with jets and either two isolated leptons (electrons or muons) with the same electric charge, or at least three isolated leptons. A data sample of proton-proton collisions at root s = 13 TeV recorded with the ATLAS detector at the Large Hadron Collider between 2015 and 2018, corresponding to a total integrated luminosity of 139 fb(-1), is used for the search. No significant excess over the Standard Model expectation is observed. The results are interpreted in simplified supersymmetric models featuring both R-parity conservation and R-parity violation, raising the exclusion limits beyond those of previous ATLAS searches to 1600 GeV for gluino masses and 750 GeV for bottom and top squark masses in these scenarios. KW - Hadron-Hadron scattering (experiments) KW - Supersymmetry Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-277538 IS - 6 ER - TY - JOUR A1 - Krauss, Jochen A1 - Vikuk, Veronika A1 - Young, Carolyn A. A1 - Krischke, Markus A1 - Mueller, Martin J. A1 - Baerenfaller, Katja T1 - Correction: Krauss, J., et al. Epichloë endophyte infection rates and alkaloid content in commercially available grass seed mixtures in Europe. Microorganisms 2020, 8, 498 JF - Microorganisms N2 - No abstract available. KW - Epichloë KW - endophyte Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-216254 SN - 2076-2607 VL - 8 IS - 10 ER - TY - JOUR A1 - Paisdzior, Sarah A1 - Dimitriou, Ioanna Maria A1 - Schöpe, Paul Curtis A1 - Annibale, Paolo A1 - Scheerer, Patrick A1 - Krude, Heiko A1 - Lohse, Martin J. A1 - Biebermann, Heike A1 - Kühnen, Peter T1 - Differential signaling profiles of MC4R mutations with three different ligands JF - International Journal of Molecular Sciences N2 - The melanocortin 4 receptor (MC4R) is a key player in hypothalamic weight regulation and energy expenditure as part of the leptin–melanocortin pathway. Mutations in this G protein coupled receptor (GPCR) are the most common cause for monogenetic obesity, which appears to be mediated by changes in the anorectic action of MC4R via G\(_S\)-dependent cyclic adenosine-monophosphate (cAMP) signaling as well as other signaling pathways. To study potential bias in the effects of MC4R mutations between the different signaling pathways, we investigated three major MC4R mutations: a G\(_S\) loss-of-function (S127L) and a G\(_S\) gain-of-function mutant (H158R), as well as the most common European single nucleotide polymorphism (V103I). We tested signaling of all four major G protein families plus extracellular regulated kinase (ERK) phosphorylation and β-arrestin2 recruitment, using the two endogenous agonists, α- and β-melanocyte stimulating hormone (MSH), along with a synthetic peptide agonist (NDP-α-MSH). The S127L mutation led to a full loss-of-function in all investigated pathways, whereas V103I and H158R were clearly biased towards the G\(_{q/11}\) pathway when challenged with the endogenous ligands. These results show that MC4R mutations can cause vastly different changes in the various MC4R signaling pathways and highlight the importance of a comprehensive characterization of receptor mutations. KW - Melanocortin 4 receptor (MC4R) KW - Melanocyte stimulating hormones MSH KW - G protein coupled receptor (GPCR) KW - biased signaling Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-285108 SN - 1422-0067 VL - 21 IS - 4 ER - TY - JOUR A1 - Baur, Florentin A1 - Nietzer, Sarah L. A1 - Kunz, Meik A1 - Saal, Fabian A1 - Jeromin, Julian A1 - Matschos, Stephanie A1 - Linnebacher, Michael A1 - Walles, Heike A1 - Dandekar, Thomas A1 - Dandekar, Gudrun T1 - Connecting cancer pathways to tumor engines: a stratification tool for colorectal cancer combining human in vitro tissue models with boolean in silico models JF - Cancers N2 - To improve and focus preclinical testing, we combine tumor models based on a decellularized tissue matrix with bioinformatics to stratify tumors according to stage-specific mutations that are linked to central cancer pathways. We generated tissue models with BRAF-mutant colorectal cancer (CRC) cells (HROC24 and HROC87) and compared treatment responses to two-dimensional (2D) cultures and xenografts. As the BRAF inhibitor vemurafenib is—in contrast to melanoma—not effective in CRC, we combined it with the EGFR inhibitor gefitinib. In general, our 3D models showed higher chemoresistance and in contrast to 2D a more active HGFR after gefitinib and combination-therapy. In xenograft models murine HGF could not activate the human HGFR, stressing the importance of the human microenvironment. In order to stratify patient groups for targeted treatment options in CRC, an in silico topology with different stages including mutations and changes in common signaling pathways was developed. We applied the established topology for in silico simulations to predict new therapeutic options for BRAF-mutated CRC patients in advanced stages. Our in silico tool connects genome information with a deeper understanding of tumor engines in clinically relevant signaling networks which goes beyond the consideration of single drivers to improve CRC patient stratification. KW - in silico simulation KW - 3D tissue models KW - colorectal cancer KW - BRAF mutation KW - targeted therapy KW - stratification Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-193798 SN - 2072-6694 VL - 12 IS - 1 ER - TY - JOUR A1 - Hoffmann, Mareike A. A1 - Pieczykolan, Aleks A1 - Koch, Iring A1 - Huestegge, Lynn T1 - Two sources of task prioritization: The interplay of effector-based and task order-based capacity allocation in the PRP paradigm JF - Attention, Perception, & Psychophysics N2 - When processing of two tasks overlaps, performance is known to suffer. In the well-established psychological refractory period (PRP) paradigm, tasks are triggered by two stimuli with a short temporal delay (stimulus onset asynchrony; SOA), thereby allowing control of the degree of task overlap. A decrease of the SOA reliably yields longer RTs of the task associated with the second stimulus (Task 2) while performance in the other task (Task 1) remains largely unaffected. This Task 2-specific SOA effect is usually interpreted in terms of central capacity limitations. Particularly, it has been assumed that response selection in Task 2 is delayed due to the allocation of less capacity until this process has been completed in Task 1. Recently, another important factor determining task prioritization has been proposed—namely, the particular effector systems associated with tasks. Here, we study both sources of task prioritization simultaneously by systematically combining three different effector systems (pairwise combinations of oculomotor, vocal, and manual responses) in the PRP paradigm. Specifically, we asked whether task order-based task prioritization (SOA effect) is modulated as a function of Task 2 effector system. The results indicate a modulation of SOA effects when the same (oculomotor) Task 1 is combined with a vocal versus a manual Task 2. This is incompatible with the assumption that SOA effects are solely determined by Task 1 response selection duration. Instead, they support the view that dual-task processing bottlenecks are resolved by establishing a capacity allocation scheme fed by multiple input factors, including attentional weights associated with particular effector systems. KW - cognitive and attentional control KW - dual-task performance KW - dual task procedures (PRP) Introduction In everyday Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-235365 SN - 1943-3921 VL - 82 ER - TY - JOUR A1 - Beer, Katharina A1 - Helfrich-Förster, Charlotte T1 - Model and Non-model Insects in Chronobiology JF - Frontiers in Behavioral Neuroscience N2 - The fruit fly Drosophila melanogaster is an established model organism in chronobiology, because genetic manipulation and breeding in the laboratory are easy. The circadian clock neuroanatomy in D. melanogaster is one of the best-known clock networks in insects and basic circadian behavior has been characterized in detail in this insect. Another model in chronobiology is the honey bee Apis mellifera, of which diurnal foraging behavior has been described already in the early twentieth century. A. mellifera hallmarks the research on the interplay between the clock and sociality and complex behaviors like sun compass navigation and time-place-learning. Nevertheless, there are aspects of clock structure and function, like for example the role of the clock in photoperiodism and diapause, which can be only insufficiently investigated in these two models. Unlike high-latitude flies such as Chymomyza costata or D. ezoana, cosmopolitan D. melanogaster flies do not display a photoperiodic diapause. Similarly, A. mellifera bees do not go into “real” diapause, but most solitary bee species exhibit an obligatory diapause. Furthermore, sociality evolved in different Hymenoptera independently, wherefore it might be misleading to study the social clock only in one social insect. Consequently, additional research on non-model insects is required to understand the circadian clock in Diptera and Hymenoptera. In this review, we introduce the two chronobiology model insects D. melanogaster and A. mellifera, compare them with other insects and show their advantages and limitations as general models for insect circadian clocks. KW - circadian clock KW - complex behavior KW - diapause KW - sociality KW - Drosophila melanogaster KW - Apis mellifera Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-218721 SN - 1662-5153 VL - 14 ER - TY - JOUR A1 - Bae, Soyeon A1 - Heidrich, Lea A1 - Levick, Shaun R. A1 - Gossner, Martin M. A1 - Seibold, Sebastian A1 - Weisser, Wolfgang W. A1 - Magdon, Paul A1 - Serebryanyk, Alla A1 - Bässler, Claus A1 - Schäfer, Deborah A1 - Schulze, Ernst-Detlef A1 - Doerfler, Inken A1 - Müller, Jörg A1 - Jung, Kirsten A1 - Heurich, Marco A1 - Fischer, Markus A1 - Roth, Nicolas A1 - Schall, Peter A1 - Boch, Steffen A1 - Wöllauer, Stephan A1 - Renner, Swen C. A1 - Müller, Jörg T1 - Dispersal ability, trophic position and body size mediate species turnover processes: Insights from a multi-taxa and multi-scale approach JF - Diversity and Distribution N2 - Aim: Despite increasing interest in β-diversity, that is the spatial and temporal turnover of species, the mechanisms underlying species turnover at different spatial scales are not fully understood, although they likely differ among different functional groups. We investigated the relative importance of dispersal limitations and the environmental filtering caused by vegetation for local, multi-taxa forest communities differing in their dispersal ability, trophic position and body size. Location: Temperate forests in five regions across Germany. Methods: In the inter-region analysis, the independent and shared effects of the regional spatial structure (regional species pool), landscape spatial structure (dispersal limitation) and environmental factors on species turnover were quantified with a 1-ha grain across 11 functional groups in up to 495 plots by variation partitioning. In the intra-region analysis, the relative importance of three environmental factors related to vegetation (herb and tree layer composition and forest physiognomy) and spatial structure for species turnover was determined. Results: In the inter-region analysis, over half of the explained variation in community composition (23% of the total explained 35%) was explained by the shared effects of several factors, indicative of spatially structured environmental filtering. Among the independent effects, environmental factors were the strongest on average over 11 groups, but the importance of landscape spatial structure increased for less dispersive functional groups. In the intra-region analysis, the independent effect of plant species composition had a stronger influence on species turnover than forest physiognomy, but the relative importance of the latter increased with increasing trophic position and body size. Main conclusions: Our study revealed that the mechanisms structuring assemblage composition are associated with the traits of functional groups. Hence, conservation frameworks targeting biodiversity of multiple groups should cover both environmental and biogeographical gradients. Within regions, forest management can enhance β-diversity particularly by diversifying tree species composition and forest physiognomy. KW - body size KW - dispersal ability KW - environmental filtering KW - forest physiognomy KW - neutral processes KW - plant composition KW - regional species pool KW - species turnover KW - trophic position KW - β-diversity Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-236117 VL - 27 IS - 3 ER - TY - JOUR A1 - Jessen, Christina A1 - Kreß, Julia K. C. A1 - Baluapuri, Apoorva A1 - Hufnagel, Anita A1 - Schmitz, Werner A1 - Kneitz, Susanne A1 - Roth, Sabine A1 - Marquardt, André A1 - Appenzeller, Silke A1 - Ade, Casten P. A1 - Glutsch, Valerie A1 - Wobser, Marion A1 - Friedmann-Angeli, José Pedro A1 - Mosteo, Laura A1 - Goding, Colin R. A1 - Schilling, Bastian A1 - Geissinger, Eva A1 - Wolf, Elmar A1 - Meierjohann, Svenja T1 - The transcription factor NRF2 enhances melanoma malignancy by blocking differentiation and inducing COX2 expression JF - Oncogene N2 - The transcription factor NRF2 is the major mediator of oxidative stress responses and is closely connected to therapy resistance in tumors harboring activating mutations in the NRF2 pathway. In melanoma, such mutations are rare, and it is unclear to what extent melanomas rely on NRF2. Here we show that NRF2 suppresses the activity of the melanocyte lineage marker MITF in melanoma, thereby reducing the expression of pigmentation markers. Intriguingly, we furthermore identified NRF2 as key regulator of immune-modulating genes, linking oxidative stress with the induction of cyclooxygenase 2 (COX2) in an ATF4-dependent manner. COX2 is critical for the secretion of prostaglandin E2 and was strongly induced by H\(_2\)O\(_2\) or TNFα only in presence of NRF2. Induction of MITF and depletion of COX2 and PGE2 were also observed in NRF2-deleted melanoma cells in vivo. Furthermore, genes corresponding to the innate immune response such as RSAD2 and IFIH1 were strongly elevated in absence of NRF2 and coincided with immune evasion parameters in human melanoma datasets. Even in vitro, NRF2 activation or prostaglandin E2 supplementation blunted the induction of the innate immune response in melanoma cells. Transcriptome analyses from lung adenocarcinomas indicate that the observed link between NRF2 and the innate immune response is not restricted to melanoma. KW - NRF2 KW - melanoma malignancy KW - COX2 expression Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-235064 SN - 0950-9232 VL - 39 ER -