TY - JOUR A1 - Ullmann, Tobias A1 - Sauerbrey, Julia A1 - Hoffmeister, Dirk A1 - May, Simon Matthias A1 - Baumhauer, Roland A1 - Bubenzer, Olaf T1 - Assessing Spatiotemporal Variations of Sentinel-1 InSAR Coherence at Different Time Scales over the Atacama Desert (Chile) between 2015 and 2018 JF - Remote Sensing N2 - This study investigates synthetic aperture radar (SAR) time series of the Sentinel-1 mission acquired over the Atacama Desert, Chile, between March 2015 and December 2018. The contribution analyzes temporal and spatial variations of Sentinel-1 interferometric SAR (InSAR) coherence and exemplarily illustrates factors that are responsible for observed signal differences. The analyses are based on long temporal baselines (365–1090 days) and temporally dense time series constructed with short temporal baselines (12–24 days). Results are compared to multispectral data of Sentinel-2, morphometric features of the digital elevation model (DEM) TanDEM-X WorldDEM™, and to a detailed governmental geographic information system (GIS) dataset of the local hydrography. Sentinel-1 datasets are suited for generating extensive, nearly seamless InSAR coherence mosaics covering the entire Atacama Desert (>450 × 1100 km) at a spatial resolution of 20 × 20 meter per pixel. Temporal baselines over several years lead only to very minor decorrelation, indicating a very high signal stability of C-Band in this region, especially in the hyperarid uplands between the Coastal Cordillera and the Central Depression. Signal decorrelation was associated with certain types of surface cover (e.g., water or aeolian deposits) or with actual surface dynamics (e.g., anthropogenic disturbance (mining) or fluvial activity and overland flow). Strong rainfall events and fluvial activity in the periods 2015 to 2016 and 2017 to 2018 caused spatial patterns with significant signal decorrelation; observed linear coherence anomalies matched the reference channel network and indicated actual episodic and sporadic discharge events. In the period 2015–2016, area-wide loss of coherence appeared as strip-like patterns of more than 80 km length that matched the prevailing wind direction. These anomalies, and others observed in that period and in the period 2017–2018, were interpreted to be caused by overland flow of high magnitude, as their spatial location matched well with documented heavy rainfall events that showed cumulative precipitation amounts of more than 20 mm. KW - Chile KW - Atacama KW - Sentinel-1 KW - InSAR KW - coherence KW - geomorphology Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-193836 SN - 2072-4292 VL - 11 IS - 24 ER - TY - JOUR A1 - Nill, Leon A1 - Ullmann, Tobias A1 - Kneisel, Christof A1 - Sobiech-Wolf, Jennifer A1 - Baumhauer, Roland T1 - Assessing Spatiotemporal Variations of Landsat Land Surface Temperature and Multispectral Indices in the Arctic Mackenzie Delta Region between 1985 and 2018 JF - Remote Sensing N2 - Air temperatures in the Arctic have increased substantially over the last decades, which has extensively altered the properties of the land surface. Capturing the state and dynamics of Land Surface Temperatures (LSTs) at high spatial detail is of high interest as LST is dependent on a variety of surficial properties and characterizes the land–atmosphere exchange of energy. Accordingly, this study analyses the influence of different physical surface properties on the long-term mean of the summer LST in the Arctic Mackenzie Delta Region (MDR) using Landsat 30 m-resolution imagery between 1985 and 2018 by taking advantage of the cloud computing capabilities of the Google Earth Engine. Multispectral indices, including the Normalized Difference Vegetation Index (NDVI), Normalized Difference Water Index (NDWI) and Tasseled Cap greenness (TCG), brightness (TCB), and wetness (TCW) as well as topographic features derived from the TanDEM-X digital elevation model are used in correlation and multiple linear regression analyses to reveal their influence on the LST. Furthermore, surface alteration trends of the LST, NDVI, and NDWI are revealed using the Theil-Sen (T-S) regression method. The results indicate that the mean summer LST appears to be mostly influenced by the topographic exposition as well as the prevalent moisture regime where higher evapotranspiration rates increase the latent heat flux and cause a cooling of the surface, as the variance is best explained by the TCW and northness of the terrain. However, fairly diverse model outcomes for different regions of the MDR (R2 from 0.31 to 0.74 and RMSE from 0.51 °C to 1.73 °C) highlight the heterogeneity of the landscape in terms of influential factors and suggests accounting for a broad spectrum of different factors when modeling mean LSTs. The T-S analysis revealed large-scale wetting and greening trends with a mean decadal increase of the NDVI/NDWI of approximately +0.03 between 1985 and 2018, which was mostly accompanied by a cooling of the land surface given the inverse relationship between mean LSTs and vegetation and moisture conditions. Disturbance through wildfires intensifies the surface alterations locally and lead to significantly cooler LSTs in the long-term compared to the undisturbed surroundings. KW - LST KW - thermal remote sensing KW - Landsat time series KW - arctic greening KW - Google Earth Engine Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-193301 SN - 2072-4292 VL - 11 IS - 19 ER - TY - JOUR A1 - Kammerer, Klaus A1 - Hoppenstedt, Burkhard A1 - Pryss, Rüdiger A1 - Stökler, Steffen A1 - Allgaier, Johannes A1 - Reichert, Manfred T1 - Anomaly Detections for Manufacturing Systems Based on Sensor Data—Insights into Two Challenging Real-World Production Settings JF - Sensors N2 - o build, run, and maintain reliable manufacturing machines, the condition of their components has to be continuously monitored. When following a fine-grained monitoring of these machines, challenges emerge pertaining to the (1) feeding procedure of large amounts of sensor data to downstream processing components and the (2) meaningful analysis of the produced data. Regarding the latter aspect, manifold purposes are addressed by practitioners and researchers. Two analyses of real-world datasets that were generated in production settings are discussed in this paper. More specifically, the analyses had the goals (1) to detect sensor data anomalies for further analyses of a pharma packaging scenario and (2) to predict unfavorable temperature values of a 3D printing machine environment. Based on the results of the analyses, it will be shown that a proper management of machines and their components in industrial manufacturing environments can be efficiently supported by the detection of anomalies. The latter shall help to support the technical evangelists of the production companies more properly. KW - anomaly detection KW - sensor data KW - machine learning KW - production machines Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-193885 SN - 1424-8220 VL - 19 IS - 24 ER - TY - JOUR A1 - Gebert, Friederike A1 - Steffan-Dewenter, Ingolf A1 - Moretto, Philippe A1 - Peters, Marcell K. T1 - Climate rather than dung resources predict dung beetle abundance and diversity along elevational and land use gradients on Mt. Kilimanjaro JF - Journal of Biogeography N2 - Aim: While elevational gradients in species richness constitute some of the best depicted patterns in ecology, there is a large uncertainty concerning the role of food resource availability for the establishment of diversity gradients in insects. Here, we analysed the importance of climate, area, land use and food resources for determining diversity gradients of dung beetles along extensive elevation and land use gradients on Mt. Kilimanjaro, Tanzania. Location: Mt. Kilimanjaro, Tanzania. Taxon: Scarabaeidae (Coleoptera). Methods: Dung beetles were recorded with baited pitfall traps at 66 study plots along a 3.6 km elevational gradient. In order to quantify food resources for the dung beetle community in form of mammal defecation rates, we assessed mammalian diversity and biomass with camera traps. Using a multi‐model inference framework and path analysis, we tested the direct and indirect links between climate, area, land use and mammal defecation rates on the species richness and abundance of dung beetles. Results: We found that the species richness of dung beetles declined exponentially with increasing elevation. Human land use diminished the species richness of functional groups exhibiting complex behaviour but did not have a significant influence on total species richness. Path analysis suggested that climate, in particular temperature and to a lesser degree precipitation, were the most important predictors of dung beetle species richness while mammal defecation rate was not supported as a predictor variable. Main conclusions: Along broad climatic gradients, dung beetle diversity is mainly limited by climatic factors rather than by food resources. Our study points to a predominant role of temperature‐driven processes for the maintenance and origination of species diversity of ectothermic organisms, which will consequently be subject to ongoing climatic changes. KW - altitudinal gradients KW - diversity gradients KW - enercy-richness hypothesis KW - food resources KW - insect abundance KW - land use KW - Scarabaeidae KW - temperature‐richness hypothesis KW - temperature‐mediated resource exploitation hypothesis KW - species‐area hypothesis Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-204701 VL - 47 IS - 2 SP - 371 EP - 381 ER - TY - JOUR A1 - Wen, Xinbo A1 - Nowak-Król, Agnieszka A1 - Nagler, Oliver A1 - Kraus, Felix A1 - Zhu, Na A1 - Zheng, Nan A1 - Müller, Matthias A1 - Schmidt, David A1 - Xie, Zengqi A1 - Würthner, Frank T1 - Tetrahydroxy-perylene bisimide embedded in zinc oxide thin film as electron transporting layer for high performance non-fullerene organic solar cells JF - Angewandte Chemie International Edition N2 - By introduction of four hydroxy (HO) groups into the two perylene bisimide (PBI) bay areas, new HO‐PBI ligands were obtained which upon deprotonation can complex ZnII ions and photosensitize semiconductive zinc oxide thin films. Such coordination is beneficial for dispersing PBI photosensitizer molecules evenly into metal oxide films to fabricate organic–inorganic hybrid interlayers for organic solar cells. Supported by the photoconductive effect of the ZnO:HO‐PBI hybrid interlayers, improved electron collection and transportation is achieved in fullerene and non‐fullerene polymer solar cell devices, leading to remarkable power conversion efficiencies of up to 15.95 % for a non‐fullerene based organic solar cell. KW - hydroxylation KW - metal complexenes KW - perylene bisimide KW - photoconductive interlayer KW - solar cells Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-204723 VL - 58 IS - 37 ER - TY - JOUR A1 - Hovestadt, Thomas A1 - Thomas, Jeremy A. A1 - Mitesser, Oliver A1 - Schönrogge, Karsten T1 - Multiple host use and the dynamics of host-switching in host-parasite systems JF - Insect Conservation and Diversity N2 - The link between multi‐host use and host switching in host–parasite interactions is a continuing area of debate. Lycaenid butterflies in the genus Maculinea, for example, exploit societies of different Myrmica ant species across their ranges, but there is only rare evidence that they simultaneously utilise multiple hosts at a local site, even where alternative hosts are present. We present a simple population‐genetic model accounting for the proportion of two alternative hosts and the fitness of parasite genotypes on each host. In agreement with standard models, we conclude that simultaneous host use is possible whenever fitness of heterozygotes on alternative hosts is not too low. We specifically focus on host‐shifting dynamics when the frequency of hosts changes. We find that (i) host shifting may proceed so rapidly that multiple host use is unlikely to be observed, (ii) back and forth transition in host use can exhibit a hysteresis loop, (iii) the parasites' host use may not be proportional to local host frequencies and be restricted to the rarer host under some conditions, and (iv) that a substantial decline in parasite abundance may typically precede a shift in host use. We conclude that focusing not just on possible equilibrium conditions but also considering the dynamics of host shifting in non‐equilibrium situations may provide added insights into host–parasite systems. KW - Host-parasite interaction KW - Maculinea butterfly KW - Myrmica ant non-equilibrium dynamics KW - population genetics Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-204747 VL - 12 IS - 6 ER - TY - JOUR A1 - Schleier, Domenik A1 - Reusch, Engelbert A1 - Lummel, Lisa A1 - Hemberger, Patrick A1 - Fischer, Ingo T1 - Threshold photoelectron spectroscopy of IO and IOH JF - ChemPhysChem N2 - Iodine oxides appear as reactive intermediates in atmospheric chemistry. Here, we investigate IO and HOI by mass‐selective threshold photoelectron spectroscopy (ms‐TPES), using synchrotron radiation. IO and HOI are generated by photolyzing iodine in the presence of ozone. For both molecules, accurate ionization energies are determined, 9.71±0.02 eV for IO and 9.79±0.02 eV for HOI. The strong spin‐spin interaction in the 3Σ− ground state of IO+ leads to an energy splitting into the Ω=0 and Ω=±1 sublevels. Upon ionization, the I−O bond shortens significantly in both molecules; thus, a vibrational progression, assigned to the I−O stretch, is apparent in both spectra. KW - ionization potential KW - radicals KW - reactive intermediates KW - photolysis KW - synchrotron radiatoren Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-204751 VL - 20 IS - 19 ER - TY - JOUR A1 - Staiger, Simona A1 - Seufert, Pascal A1 - Arand, Katja A1 - Burghardt, Markus A1 - Popp, Christian A1 - Riederer, Markus T1 - The permeation barrier of plant cuticles: uptake of active ingredients is limited by very long-chain aliphatic rather than cyclic wax compounds JF - Pest Management Science N2 - BACKGROUND: The barrier to diffusion of organic solutes across the plant cuticle is composed of waxes consisting of very long-chain aliphatic (VLCA) and, to varying degrees, cyclic compounds like pentacyclic triterpenoids. The roles of both fractions in controlling cuticular penetration by organic solutes, e.g. the active ingredients (AI) of pesticides, are unknown to date. We studied thepermeabilityof isolated leaf cuticularmembranes from Garcinia xanthochymus andPrunus laurocerasus for lipophilic azoxystrobin and theobromine as model compounds for hydrophilic AIs. RESULTS: The wax of P. laurocerasus consists of VLCA (12%) and cyclic compounds (88%), whereas VLCAs make up 97% of the wax of G. xanthochymus.We showthat treating isolated cuticles with methanol almost quantitatively releases the cyclic fraction while leaving the VLCA fraction essentially intact. All VLCAs were subsequently removed using chloroform. In both species, the permeance of the two model compounds did not change significantly after methanol treatment, whereas chloroform extraction had a large effect on organic solute permeability. CONCLUSION: The VLCA wax fractionmakes up the permeability barrier for organic solutes, whereas cyclic compounds even in high amounts have a negligible role. This is of significance when optimizing the foliar uptake of pesticides. KW - cuticular permeability KW - active ingredients KW - very long-chain aliphatic compounds KW - cyclic compounds KW - pesicicles Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-204778 VL - 75 IS - 12 ER - TY - JOUR A1 - Gehrke, Thomas A1 - Scherzad, Agmal A1 - Hagen, Rudolf A1 - Hackenberg, Stephan T1 - Risk factors for children requiring adenotonsillectomy and their impact on postoperative complications: a retrospective analysis of 2000 patients JF - Anaesthesia N2 - Adenotonsillectomies are commonly performed procedures and sleep‐disordered breathing is becoming increasingly important as an indication for surgery. Because of the higher risks in patients with obstructive sleep apnoea, the required level of postoperative care for these patients is currently under discussion, and better identification of patients at risk may reduce unnecessary postoperative monitoring. To evaluate the influence of obstructive sleep apnoea, and other risk factors, on peri‐operative complications in children requiring adenotonsillectomy, we performed a retrospective case‐control study that included 1995 patients treated between January 2009 and June 2017. In our analysis, young age (OR 3.8, 95%CI 2.1–7.1), low body weight (OR 2.6, 95%CI 1.5–4.4), obstructive sleep apnoea (OR 2.4, 95%CI 1.5–3.8), pre‐existing craniofacial or syndromal disorders (OR 2.3, 95%CI 1.4–3.8) and adenotonsillectomy, compared with adenoidectomy alone, (OR 7.9, 95%CI 4.7–13.1) were identified as risk factors for complications during or after surgery, p < 0.001. All 13 patients suffering from complications more than 3 h postoperatively had obstructive sleep apnoea plus at least one more of these risk factors. Patients at risk of postoperative complications can therefore be identified by several criteria pre‐operatively, and should be monitored postoperatively using pulse oximetry overnight. For all other patients, postoperative observation on a surgical ward without extra monitoring is sufficient. Admission to paediatric intensive care should be reserved for patients suffering serious intra‐operative complications. KW - adenotonsillectromy KW - monotoring KW - obstructive sleep apnoea KW - paediatrics KW - retrospective KW - risk factors Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-204787 VL - 74 IS - 12 ER - TY - JOUR A1 - Boetzl, Fabian A. A1 - Konle, Antonia A1 - Krauss, Jochen T1 - Aphid cards – useful model for assessing predation rates or bias prone nonsense? JF - Journal of Applied Entomology N2 - Predation on pest organisms is an essential ecosystem function supporting yields in modern agriculture. However, assessing predation rates is intricate, and they can rarely be linked directly to predator densities or functions. We tested whether sentinel prey aphid cards are useful tools to assess predation rates in the field. Therefore, we looked at aphid cards of different sizes on the ground level as well as within the vegetation. Additionally, by trapping ground‐dwelling predators, we examined whether obtained predation rates could be linked to predator densities and traits. Predation rates recorded with aphid cards were independent of aphid card size. However, predation rates on the ground level were three times higher than within the vegetation. We found both predatory carabid activity densities as well as community weighted mean body size to be good predictors for predation rates. Predation rates obtained from aphid cards are stable over card type and related to predator assemblages. Aphid cards, therefore, are a useful, efficient method for rapidly assessing the ecosystem function predation. Their use might especially be recommended for assessments on the ground level and when time and resource limitations rule out more elaborate sentinel prey methods using exclosures with living prey animals. KW - carabid beetles KW - ecosystem service KW - ground-dwelling predators KW - methods KW - natural pest control KW - sentinel prey Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-204798 VL - 144 IS - 1-2 ER - TY - JOUR A1 - Schmidt, David A1 - Stolte, Matthias A1 - Süß, Jasmin A1 - Liess, Dr. Andreas A1 - Stepanenko, Vladimir A1 - Würthner, Frank T1 - Protein-like enwrapped perylene bisimide chromophore as bright microcrystalline emitter material JF - Angewandte Chemie International Edition N2 - Strongly emissive solid‐state materials are mandatory components for many emerging optoelectronic technologies, but fluorescence is often quenched in the solid state owing to strong intermolecular interactions. The design of new organic pigments, which retain their optical properties despite their high tendency to crystallize, could overcome such limitations. Herein, we show a new material with monomer‐like absorption and emission profiles as well as fluorescence quantum yields over 90 % in its crystalline solid state. The material was synthesized by attaching two bulky tris(4‐tert‐butylphenyl)phenoxy substituents at the perylene bisimide bay positions. These substituents direct a packing arrangement with full enwrapping of the chromophore and unidirectional chromophore alignment within the crystal lattice to afford optical properties that resemble those of their natural pigment counterparts, in which chromophores are rigidly embedded in protein environments. KW - cristal engeneering KW - dyes KW - flourescence quantum yield KW - perylene bisimides KW - solid-state emitters Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-204809 VL - 58 IS - 38 ER - TY - JOUR A1 - Robinson, Thomas M. A1 - Hutmacher, Dietmar W. A1 - Dalton, Paul D. T1 - The next frontier in melt electrospinning: taming the jet JF - Advanced Functional Materials N2 - There is a specialized niche for the electrohydrodynamic jetting of melts, from biomedical products to filtration and soft matter applications. The next frontier includes optics, microfluidics, flexible electronic devices, and soft network composites in biomaterial science and soft robotics. The recent emphasis on reproducibly direct‐writing continual molten jets has enabled a spectrum of contemporary microscale 3D objects to be fabricated. One strong suit of melt processing is the capacity for the jet to solidify rapidly into a fiber, thus fixing a particular structure into position. The ability to direct‐write complex and multiscaled architectures and structures has greatly contributed to a large number of recent studies, explicitly, toward fiber–hydrogel composites and fugitive inks, and has expanded into several biomedical applications such as cartilage, skin, periosteum, and cardiovascular tissue engineering. Following the footsteps of a publication that summarized melt electrowriting literature up to 2015, the most recent literature from then until now is reviewed to provide a continuous and comprehensive timeline that demonstrates the latest advances as well as new perspectives for this emerging technology. KW - 3D printing KW - additive manufacturing KW - eletrhydrodynamic KW - melt electrospinning writing Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-204819 VL - 29 ER - TY - JOUR A1 - Budiman, Yudha P. A1 - Friedrich, Alexandra A1 - Radius, Udo A1 - Marder, Todd B. T1 - Copper-catalysed Suzuki-Miyaura cross-coupling of highly fluorinated aryl boronate esters with aryl iodides and bromides and fluoroarene-arene π-stacking interactions in the products JF - ChemCatChem N2 - A combination of copper iodide and phenanthroline as the ligand is an efficient catalyst for Suzuki‐Miyaura cross‐coupling of highly fluorinated boronate esters (aryl−Bpin) with aryl iodides and bromides to generate fluorinated biaryls in good to excellent yields. This method represents a nice alternative to traditional cross‐coupling methods which require palladium catalysts and stoichiometric amounts of silver oxide. We note that π⋅⋅⋅π stacking interactions dominate the molecular packing in the partly fluorinated biaryl crystals investigated herein. They are present either between the arene and perfluoroarene, or solely between arenes or perfluoroarenes, respectively. KW - homogeneous catalysis KW - boron KW - boronate KW - fluorine KW - fluoroarene Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-204839 VL - 11 IS - 21 ER - TY - JOUR A1 - Lorkowski, Jan A1 - Krahfuss, Mirjam A1 - Kubicki, Maciej A1 - Radius, Udo A1 - Pietraszuk, Cezary T1 - Intramolecular ring expansion reaction (RER) and intermolecular coordination of in situ generated Cyclic (Amino)(Aryl)Carbenes (cAArCs) JF - Chemistry - A European Journal N2 - Cyclic (amino)(aryl)carbenes (cAArCs) based on the isoindoline core were successfully generated in situ by α‐elimination of 3‐alkoxyisoindolines at high temperatures or by deprotonation of isoindol‐2‐ium chlorides with sodium or copper(I) acetates at low temperatures. 3‐Alkoxy‐isoindolines 2 a ,b‐OR (R=Me, Et, i Pr) have been prepared in high yields by the addition of a solution of 2‐aryl‐1,1‐diphenylisoindol‐2‐ium triflate (1 a ,b‐OTf ; a : aryl=Dipp=2,6‐diisopropylphenyl; b : Mesityl‐, Mes=2,4,6‐trimethylphenyl) to the corresponding alcohol (ROH) with NEt3 at room temperature. Furthermore, the reaction of 2 a ,b‐OMe in diethyl ether with a tenfold excess of hydrochloric acid led to the isolation of the isoindol‐2‐ium chlorides 1 a ,b‐Cl in high yields. The thermally generated cAArC reacts with sulfur to form the thioamide 3 a . Without any additional trapping reagent, in situ generation of 1,1‐diphenylisoidolin‐3‐ylidenes does not lead to the isolation of these compounds, but to the reaction products of the insertion of the carbene carbon atom into an ortho C−H bond of a phenyl substituent, followed by ring‐expansion reaction; namely, anthracene derivatives 9‐N(H)aryl‐10‐Ph‐C14H8 4 a ,b (a : Dipp; b : Mes). These compounds are conveniently synthesized by deprotonation of the isoindol‐2‐ium chlorides with sodium acetate in high yields. Deprotonation of 1 a‐Cl with copper(I) acetate at low temperatures afforded a mixture of 4 a and the corresponding cAArC copper(I) chloride 5 a , and allowed the isolation and structural characterization of the first example of a cAArC copper complex of general formula [(cAArC)CuCl]. KW - cAArC KW - complexes KW - copper KW - NHC KW - ring-expansion reaction Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-204847 VL - 25 IS - 48 ER - TY - JOUR A1 - Figueiredo, Ludmilla A1 - Krauss, Jochen A1 - Steffan-Dewenter, Ingolf A1 - Cabral, Juliano Sarmento T1 - Understanding extinction debts: spatio-temporal scales, mechanisms and a roadmap for future research JF - Ecography N2 - Extinction debt refers to delayed species extinctions expected as a consequence of ecosystem perturbation. Quantifying such extinctions and investigating long‐term consequences of perturbations has proven challenging, because perturbations are not isolated and occur across various spatial and temporal scales, from local habitat losses to global warming. Additionally, the relative importance of eco‐evolutionary processes varies across scales, because levels of ecological organization, i.e. individuals, (meta)populations and (meta)communities, respond hierarchically to perturbations. To summarize our current knowledge of the scales and mechanisms influencing extinction debts, we reviewed recent empirical, theoretical and methodological studies addressing either the spatio–temporal scales of extinction debts or the eco‐evolutionary mechanisms delaying extinctions. Extinction debts were detected across a range of ecosystems and taxonomic groups, with estimates ranging from 9 to 90% of current species richness. The duration over which debts have been sustained varies from 5 to 570 yr, and projections of the total period required to settle a debt can extend to 1000 yr. Reported causes of delayed extinctions are 1) life‐history traits that prolong individual survival, and 2) population and metapopulation dynamics that maintain populations under deteriorated conditions. Other potential factors that may extend survival time such as microevolutionary dynamics, or delayed extinctions of interaction partners, have rarely been analyzed. Therefore, we propose a roadmap for future research with three key avenues: 1) the microevolutionary dynamics of extinction processes, 2) the disjunctive loss of interacting species and 3) the impact of multiple regimes of perturbation on the payment of debts. For their ability to integrate processes occurring at different levels of ecological organization, we highlight mechanistic simulation models as tools to address these knowledge gaps and to deepen our understanding of extinction dynamics. KW - Anthropocene KW - biotic interaction KW - extinction dynamics KW - mechanistic modelling KW - time lag KW - transient dynamics Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-204859 VL - 42 IS - 12 ER - TY - JOUR A1 - Pauls, Dennis A1 - Hamarat, Yasmin A1 - Trufasu, Luisa A1 - Schendzielorz, Tim M. A1 - Gramlich, Gertrud A1 - Kahnt, Jörg A1 - Vanselow, Jens A1 - Schlosser, Andreas A1 - Wegener, Christian T1 - Drosophila carboxypeptidase D (SILVER) is a key enzyme in neuropeptide processing required to maintain locomotor activity levels and survival rate JF - European Journal of Neuroscience N2 - Neuropeptides are processed from larger preproproteins by a dedicated set of enzymes. The molecular and biochemical mechanisms underlying preproprotein processing and the functional importance of processing enzymes are well‐characterised in mammals, but little studied outside this group. In contrast to mammals, Drosophila melanogaster lacks a gene for carboxypeptidase E (CPE ), a key enzyme for mammalian peptide processing. By combining peptidomics and neurogenetics, we addressed the role of carboxypeptidase D (dCPD ) in global neuropeptide processing and selected peptide‐regulated behaviours in Drosophila . We found that a deficiency in dCPD results in C‐terminally extended peptides across the peptidome, suggesting that dCPD took over CPE function in the fruit fly. dCPD is widely expressed throughout the nervous system, including peptidergic neurons in the mushroom body and neuroendocrine cells expressing adipokinetic hormone. Conditional hypomorphic mutation in the dCPD ‐encoding gene silver in the larva causes lethality, and leads to deficits in starvation‐induced hyperactivity and appetitive gustatory preference, as well as to reduced viability and activity levels in adults. A phylogenomic analysis suggests that loss of CPE is not common to insects, but only occurred in Hymenoptera and Diptera. Our results show that dCPD is a key enzyme for neuropeptide processing and peptide‐regulated behaviour in Drosophila . dCPD thus appears as a suitable target to genetically shut down total neuropeptide production in peptidergic neurons. The persistent occurrence of CPD in insect genomes may point to important further CPD functions beyond neuropeptide processing which cannot be fulfilled by CPE. KW - direct muss spectrometric profiling KW - friut fly behaviour KW - M14 carboxypeptidasses KW - peptidomoics KW - protein processing Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-204863 VL - 50 IS - 9 ER - TY - JOUR A1 - Lübtow, Michael M. A1 - Marciniak, Henning A1 - Schmiedel, Alexander A1 - Roos, Markus A1 - Lambert, Christoph A1 - Luxenhofer, Robert T1 - Ultra-high to ultra-low drug loaded micelles: Probing host-guest interactions by fluorescence spectroscopy JF - Chemistry - A European Journal N2 - Polymer micelles are an attractive means to solubilize water insoluble compounds such as drugs. Drug loading, formulations stability and control over drug release are crucial factors for drug‐loaded polymer micelles. The interactions between the polymeric host and the guest molecules are considered critical to control these factors but typically barely understood. Here, we compare two isomeric polymer micelles, one of which enables ultra‐high curcumin loading exceeding 50 wt.%, while the other allows a drug loading of only 25 wt.%. In the low capacity micelles, steady‐state fluorescence revealed a very unusual feature of curcumin fluorescence, a high energy emission at 510 nm. Time‐resolved fluorescence upconversion showed that the fluorescence life time of the corresponding species is too short in the high‐capacity micelles, preventing an observable emission in steady‐state. Therefore, contrary to common perception, stronger interactions between host and guest can be detrimental to the drug loading in polymer micelles. KW - curcumin KW - drug delivery KW - fluorenscence KW - poly(2-oxazine) KW - pol(2-oxazoline) KW - Polymer-drug interaction KW - upconversion Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-206128 VL - 25 IS - 54 ER - TY - JOUR A1 - Wegener, Sonja A1 - Sauer, Otto A. T1 - The effective point of measurement for depth-dose measurements in small MV photon beams with different detectors JF - Medical Physics N2 - Purpose: The effective point of measurement (EPOM) of cylindrical ionization chambers differs from their geometric center. The exact shift depends on chamber construction details, above all the chamber size, and to some degree on the field-size and beam quality. It generally decreases as the chamber dimensions get smaller. In this work, effective points of measurement in small photon fields of a range of cylindrical chambers of different sizes are investigated, including small chambers that have not been studied previously. Methods: In this investigation, effective points of measurement for different ionization chambers (Farmer type, scanning chambers, micro-ionization chambers) and solid state detectors were determined by measuring depth-ionization curves in a 6 MV beam in field sizes between 2 9 2 cm2 and 10 9 10 cm2 and comparing those curves with curves measured with plane-parallel chambers. Results: It was possible to average the results to one shift per detector, as the results were sufficiently independent of the studied field sizes. For cylindrical ion chambers, shifts of the EPOM were determined to be between 0.49 and 0.30 times the inner chamber radius from the reference point. Conclusions: We experimentally confirmed the previously reported decrease of the EPOM shift with decreasing detector size. Highly accurate data for a large range of detectors, including new very small ones, were determined. Thus, small chambers noticeably differ from the 0.5-times to 0.6-times the inner chamber radius recommendations in current dosimetry protocols. The detector-individual EPOMs need to be considered for measurements of depth-dose curves. KW - depth dose curves KW - effective point of measurement KW - ionization chambers KW - micro-chambers Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-206148 VL - 46 IS - 11 ER - TY - JOUR A1 - Kitzenmaier, Alexandra A1 - Schaefer, Natascha A1 - Kasaragod, Vikram Babu A1 - Polster, Tilman A1 - Hantschmann, Ralph A1 - Schindelin, Hermann A1 - Villmann, Carmen T1 - The P429L loss of function mutation of the human glycine transporter 2 associated with hyperekplexia JF - European Journal of Neuroscience N2 - Glycine transporter 2 (GlyT2) mutations across the entire sequence have been shown to represent the presynaptic component of the neurological disease hyperekplexia. Dominant, recessive and compound heterozygous mutations have been identified, most of them leading to impaired glycine uptake. Here, we identified a novel loss of function mutation of the GlyT2 resulting from an amino acid exchange of proline 429 to leucine in a family with both parents being heterozygous carriers. A homozygous child suffered from severe neuromotor deficits. We characterised the GlyT2P429L variant at the molecular, cellular and protein level. Functionality was determined by glycine uptake assays. Homology modelling revealed that the mutation localises to α‐helix 5, presumably disrupting the integrity of this α‐helix. GlyT2P429L shows protein trafficking through various intracellular compartments to the cellular surface. However, the protein expression at the whole cell level was significantly reduced. Although present at the cellular surface, GlyT2P429L demonstrated a loss of protein function. Coexpression of the mutant with the wild‐type protein, reflecting the situation in the parents, did not affect transporter function, thus explaining their non‐symptomatic phenotype. Nevertheless, when the mutant was expressed in excess compared with the wild‐type protein, glycine uptake was significantly reduced. Thus, these data demonstrate that the proline residue at position 429 is structurally important for the correct formation of α‐helix 5. The failure in functionality of the mutated GlyT2 is most probably due to structural changes localised in close proximity to the sodium‐binding site of the transporter. KW - glycine transporter 2 KW - glyvine uptake KW - loss of function KW - presynaptic hyperekplexia KW - protein transport KW - structural disruption Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-206158 VL - 50 IS - 12 ER - TY - JOUR A1 - Evdokimov, Dimitar A1 - Frank, Johanna A1 - Klitsch, Alexander A1 - Unterecker, Stefan A1 - Warrings, Bodo A1 - Serra, Jordi A1 - Papagianni, Aikaterini A1 - Saffer, Nadine A1 - Meyer zu Altenschildesche, Caren A1 - Kampik, Daniel A1 - Malik, Rayaz A. A1 - Sommer, Claudia A1 - Üceyler, Nurcan T1 - Reduction of skin innervation is associated with a severe fibromyalgia phenotype JF - Annals of Neurology N2 - Objective: To assess patterns and impact of small nerve fiber dysfunction and pathology in patients with fibromyalgia syndrome (FMS). Methods: One hundred seventeen women with FMS underwent neurological examination, questionnaire assessment, neurophysiology assessment, and small fiber tests: skin punch biopsy, corneal confocal microscopy, microneurography, quantitative sensory testing including C-tactile afferents, and pain-related evoked potentials. Data were compared with those of women with major depressive disorder and chronic widespread pain (MD-P) and healthy women. Results: Intraepidermal nerve fiber density (IENFD) was reduced at different biopsy sites in 63% of FMS patients (MDP: 10%, controls: 18%; p < 0.001 for each). We found 4 patterns of skin innervation in FMS: normal, distally reduced, proximally reduced, and both distally and proximally reduced (p < 0.01 for each compared to controls). Microneurography revealed initial activity-dependent acceleration of conduction velocity upon low frequencies of stimulation in 1A fibers, besides 1B fiber spontaneous activity and mechanical sensitization in FMS patients. FMS patients had elevated warm detection thresholds (p < 0.01), impaired C-tactile afferents (p < 0.05), and reduced amplitudes (p < 0.001) of pain-related evoked potentials compared to controls. Compared to FMS patients with normal skin innervation, those with generalized IENFD reduction had higher pain intensity and impairment due to pain, higher disease burden, more stabbing pain and paresthesias, and more anxiety (p < 0.05 for each). FMS patients with generalized IENFD reduction also had lower corneal nerve fiber density (p < 0.01) and length (p < 0.05). Interpretation: The extent of small fiber pathology is related to symptom severity in FMS. This knowledge may have implications for the diagnostic classification and treatment of patients with FMS. KW - fibromyalgia Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-206168 VL - 86 IS - 4 ER - TY - JOUR A1 - Thiess, Torsten A1 - Mellerup, Soren K. A1 - Braunschweig, Holger T1 - B–B Cleavage and Ring-Expansion of a 1,4,2,3-Diazadiborinine with N-Heterocyclic Carbenes JF - Chemistry - A European Journal N2 - A 1,4,2,3‐diazadiborinine derivative was found to form Lewis adducts with strong two‐electron donors such as N‐heterocyclic and cyclic (alkyl)(amino)carbenes. Depending on the donor, some of these Lewis pairs are thermally unstable, converting to sole B,N‐embedded products upon gentle heating. The products of these reactions, which have been fully characterized by NMR spectroscopy, elemental analysis, and single‐crystal X‐ray diffraction, were identified as B,N‐heterocycles with fused 1,5,2,4‐diazadiborepine and 1,4,2‐diazaborinine rings. Computational modelling of the reaction mechanism provides insight into the formation of these unique structures, suggesting that a series of B−H, C−N, and B−B bond activation steps are responsible for these “intercalation” reactions between the 1,4,2,3‐diazadiborinine and NHCs. KW - B,N-heterocylcles KW - B-B bond activation KW - diazadiborinines KW - NHCs KW - ring-expansion reactions Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-206173 VL - 25 IS - 59 ER - TY - JOUR A1 - He, Jiang A1 - Rauch, Florian A1 - Friedrich, Alexandra A1 - Sieh, Daniel A1 - Ribbeck, Tatjana A1 - Krummenacher, Ivo A1 - Braunschweig, Holger A1 - Finze, Maik A1 - Marder, Todd B. T1 - N-Heterocyclic Olefins as Electron Donors in Combination with Triarylborane Acceptors: Synthesis, Optical and Electronic Properties of D-π-A Compounds JF - Chemistry - A European Journal N2 - N‐heterocyclic olefins (NHOs), relatives of N‐heterocyclic carbenes (NHCs), exhibit high nucleophilicity and soft Lewis basic character. To investigate their π‐electron donating ability, NHOs were attached to triarylborane π‐acceptors (A) giving donor (D)–π–A compounds 1–3. In addition, an enamine π‐donor analogue (4) was synthesized for comparison. UV–visible absorption studies show a larger red shift for the NHO‐containing boranes than for the enamine analogue, a relative of cyclic (alkyl)(amino) carbenes (CAACs). Solvent‐dependent emission studies indicate that 1–4 have moderate intramolecular charge‐transfer (ICT) behavior. Electrochemical investigations reveal that the NHO‐containing boranes have extremely low reversible oxidation potentials (e.g., for 3, \(E^{ox}_{1/2}\) =−0.40 V vs. ferrocene/ferrocenium, Fc/Fc\(^+\), in THF). Time‐dependent (TD) DFT calculations show that the HOMOs of 1–3 are much more destabilized than that of the enamine‐containing 4, which confirms the stronger donating ability of NHOs. KW - donor-acceptor systems KW - electrochemistry KW - photophysical prosperties KW - N-heterocyclic olefins KW - triarylboranes Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-204690 VL - 25 ER - TY - JOUR A1 - Requier, Fabrice A1 - Paillet, Yoan A1 - Laroche, Fabienne A1 - Rutschmann, Benjamin A1 - Zhang, Jie A1 - Lombardi, Fabio A1 - Svoboda, Miroslav A1 - Steffan-Dewenter, Ingolf T1 - Contribution of European forests to safeguard wild honeybee populations JF - Conservation Letters N2 - Abstract Recent studies reveal the use of tree cavities by wild honeybee colonies in European forests. This highlights the conservation potential of forests for a highly threatened component of the native entomofauna in Europe, but currently no estimate of potential wild honeybee population sizes exists. Here, we analyzed the tree cavity densities of 106 forest areas across Europe and inferred an expected population size of wild honeybees. Both forest and management types affected the density of tree cavities. Accordingly, we estimated that more than 80,000 wild honeybee colonies could be sustained in European forests. As expected, potential conservation hotspots were identified in unmanaged forests, and, surprisingly, also in other large forest areas across Europe. Our results contribute to the EU policy strategy to halt pollinator declines and reveal the potential of forest areas for the conservation of so far neglected wild honeybee populations in Europe. KW - Apis mellifera KW - Conservation KW - forest management KW - honeybees KW - native populations KW - protected forests KW - tree cavities KW - unmanaged broadleaved forests Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-204407 VL - 13 IS - 2 ER - TY - JOUR A1 - Diers, J. A1 - Wagner, J. A1 - Baum, P. A1 - Lichthardt, S. A1 - Kastner, C. A1 - Matthes, N. A1 - Löb, S. A1 - Matthes, H. A1 - Germer, C.-T. A1 - Wiegering, A. T1 - Nationwide in-hospital mortality following colonic cancer resection according to hospital volume in Germany JF - BJS Open N2 - Background: Colonic cancer is the most common cancer of the gastrointestinal tract. The aim of this study was to determine mortality rates following colonic cancer resection and the effect of hospital caseload on in-hospital mortality in Germany. Methods: Patients admitted with a diagnosis of colonic cancer undergoing colonic resection from 2012 to 2015 were identifed from a nationwide registry using procedure codes. The outcome measure was in-hospital mortality. Hospitals were ranked according to their caseload for colonic cancer resection, and patients were categorized into five subgroups on the basis of hospital volume. Results: Some 129 196 colonic cancer resections were reviewed. The overall in-house mortality rate was 5⋅8 per cent, ranging from 6⋅9 per cent (1775 of 25 657 patients) in very low-volume hospitals to 4⋅8 per cent (1239 of 25 825) in very high-volume centres (P < 0⋅001). In multivariable logistic regression analysis the risk-adjusted odds ratio for in-house mortality was 0⋅75 (95 per cent c.i. 0⋅66 to 0⋅84) in very high-volume hospitals performing a mean of 85⋅0 interventions per year, compared with that in very low-volume hospitals performing a mean of only 12⋅7 interventions annually, after adjustment for sex, age, co-morbidity, emergency procedures, prolonged mechanical ventilation and transfusion. Conclusion: In Germany, patients undergoing colonic cancer resections in high-volume hospitals had with improved outcomes compared with patients treated in low-volume hospitals Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-204385 VL - 3 IS - 5 ER - TY - JOUR A1 - Ribechini, Eliana A1 - Eckert, Ina A1 - Beilhack, Andreas A1 - Du Plessis, Nelita A1 - Walzl, Gerhard A1 - Schleicher, Ulrike A1 - Ritter, Uwe A1 - Lutz, Manfred B. T1 - Heat-killed Mycobacterium tuberculosis prime-boost vaccination induces myeloid-derived suppressor cells with spleen dendritic cell–killing capability JF - JCI Insight N2 - Tuberculosis patients and mice infected with live Mycobacterium tuberculosis accumulate high numbers of myeloid-derived suppressor cells (MDSCs). Here, we hypothesized that dead M. tuberculosis vaccines also may induce MDSCs that could impair the efficacy of vaccination. We found that repeated injections of M. tuberculosis vaccines (heat-killed M. tuberculosis in incomplete Freund’s adjuvant, such as Montanide) but not single or control vaccines without M. tuberculosis strongly expanded CD11b\(^+\) myeloid cells in the spleen, leading to T cell suppression of proliferation and killing ex vivo. Dead M. tuberculosis vaccination induced the generation of CD11b\(^+\)Ly6C\(^{hi}\)CD115\(^+\) iNOS/Nos2\(^+\) monocytic MDSCs (M-MDSCs) upon application of inflammatory or microbial activation signals. In vivo these M-MDSCs were positioned strategically in the splenic bridging channels and then positioned in the white pulp areas. Notably, within 6–24 hours, in a Nos2-dependent fashion, they produced NO to rapidly kill conventional and plasmacytoid DCs while, surprisingly, sparing T cells in vivo. Thus, we demonstrate that M. tuberculosis vaccine induced M-MDSCs do not directly suppress effector T cells in vivo but, instead, indirectly by killing DCs. Collectively, we demonstrate that M. tuberculosis booster vaccines induce M-MDSCs in the spleen that can be activated to kill DCs. Our data suggest that formation of MDSCs by M. tuberculosis vaccines should be investigated also in clinical trials. KW - Immunology KW - Infectious disease Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-201973 VL - 13 IS - 4 ER - TY - JOUR A1 - Dietrich, Georg A1 - Krebs, Jonathan A1 - Liman, Leon A1 - Fette, Georg A1 - Ertl, Maximilian A1 - Kaspar, Mathias A1 - Störk, Stefan A1 - Puppe, Frank T1 - Replicating medication trend studies using ad hoc information extraction in a clinical data warehouse JF - BMC Medical Informatics and Decision Making N2 - Background Medication trend studies show the changes of medication over the years and may be replicated using a clinical Data Warehouse (CDW). Even nowadays, a lot of the patient information, like medication data, in the EHR is stored in the format of free text. As the conventional approach of information extraction (IE) demands a high developmental effort, we used ad hoc IE instead. This technique queries information and extracts it on the fly from texts contained in the CDW. Methods We present a generalizable approach of ad hoc IE for pharmacotherapy (medications and their daily dosage) presented in hospital discharge letters. We added import and query features to the CDW system, like error tolerant queries to deal with misspellings and proximity search for the extraction of the daily dosage. During the data integration process in the CDW, negated, historical and non-patient context data are filtered. For the replication studies, we used a drug list grouped by ATC (Anatomical Therapeutic Chemical Classification System) codes as input for queries to the CDW. Results We achieve an F1 score of 0.983 (precision 0.997, recall 0.970) for extracting medication from discharge letters and an F1 score of 0.974 (precision 0.977, recall 0.972) for extracting the dosage. We replicated three published medical trend studies for hypertension, atrial fibrillation and chronic kidney disease. Overall, 93% of the main findings could be replicated, 68% of sub-findings, and 75% of all findings. One study could be completely replicated with all main and sub-findings. Conclusion A novel approach for ad hoc IE is presented. It is very suitable for basic medical texts like discharge letters and finding reports. Ad hoc IE is by definition more limited than conventional IE and does not claim to replace it, but it substantially exceeds the search capabilities of many CDWs and it is convenient to conduct replication studies fast and with high quality. KW - data warehouse KW - medication extraction KW - information extraction Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-200409 VL - 19 ER - TY - JOUR A1 - Duque, Laura A1 - Poelman, Erik H. A1 - Steffan-Dewenter, Ingolf T1 - Plant-mediated effects of ozone on herbivores depend on exposure duration and temperature JF - Scientific Reports N2 - Abiotic stress by elevated tropospheric ozone and temperature can alter plants’ metabolism, growth, and nutritional value and modify the life cycle of their herbivores. We investigated how the duration of exposure of Sinapis arvensis plants to high ozone and temperature levels affect the life cycle of the large cabbage white, Pieris brassicae. Plants were exposed to ozone-clean (control) or ozone-enriched conditions (120 ppb) for either 1 or 5 days and were afterwards kept in a greenhouse with variable temperature conditions. When given the choice, P. brassicae butterflies laid 49% fewer eggs on ozone-exposed than on control plants when the exposure lasted for 5 days, but showed no preference when exposure lasted for 1 day. The caterpillars took longer to hatch on ozone-exposed plants and at lower ambient temperatures. The ozone treatment had a positive effect on the survival of the eggs. Ozone decreased the growth of caterpillars reared at higher temperatures on plants exposed for 5 days, but not on plants exposed for 1 day. Overall, longer exposure of the plants to ozone and higher temperatures affected the life cycle of the herbivore more strongly. With global warming, the indirect impacts of ozone on herbivores are likely to become more common. KW - Ecology KW - Environmental impact Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-202805 VL - 9 ER - TY - JOUR A1 - Maniuc, Octavian A1 - Salinger, Tim A1 - Anders, Fabian A1 - Müntze, Jonas A1 - Liu, Dan A1 - Hu, Kai A1 - Ertl, Georg A1 - Frantz, Stefan A1 - Nordbeck, Peter T1 - Impella CP use in patients with non‐ischaemic cardiogenic shock JF - ESC Heart Failure N2 - Aims From the various mechanical cardiac assist devices and indications available, the use of the percutaneous intraventricular Impella CP pump is usually restricted to acute ischaemic shock or prophylactic indications in high‐risk interventions. In the present study, we investigated clinical usefulness of the Impella CP device in patients with non‐ischaemic cardiogenic shock as compared with acute ischaemia. Methods and results In this retrospective single‐centre analysis, patients who received an Impella CP at the University Hospital Würzburg between 2013 and 2017 due to non‐ischaemic cardiogenic shock were age‐matched 2:1 with patients receiving the device due to ischaemic cardiogenic shock. Inclusion criteria were therapy refractory haemodynamic instability with severe left ventricular systolic dysfunction and serum lactate >2.0 mmol/L at implantation. Basic clinical data, indications for mechanical ventricular support, and outcome were obtained in all patients with non‐ischaemic as well as ischaemic shock and compared between both groups. Continuous variables are expressed as mean ± standard deviation or median (quartiles). Categorical variables are presented as count and per cent. Twenty‐five patients had cardiogenic shock due to non‐ischaemic reasons and were compared with 50 patients with cardiogenic shock due to acute myocardial infarction. Resuscitation rates before implantation of Impella CP were high (32 vs. 42%; P = 0.402). At implantation, patients with non‐ischaemic cardiogenic shock had lower levels of high‐sensitive troponin T (110.65 [57.87–322.1] vs. 1610 [450.8–3861.5] pg/mL; P = 0.001) and lactate dehydrogenase (377 [279–608] vs. 616 [371.3–1109] U/L; P = 0.007), while age (59 ± 16 vs. 61.7 ± 11; P = 0.401), glomerular filtration rate (43.5 [33.2–59.7] vs. 48 [35.75–69] mL/min; P = 0.290), C‐reactive protein (5.17 [3.27–10.26] vs. 10.97 [3.23–17.2] mg/dL; P = 0.195), catecholamine index (30.6 [10.6–116.9] vs. 47.6 [11.7–90] μg/kg/min; P = 0.663), and serum lactate (2.6 [2.2–5.8] vs. 2.9 [1.3–6.6] mmol/L; P = 0.424) were comparable between both groups. There was a trend for longer duration of Impella support in the non‐ischaemic groups (5 [2–7.5] vs. 3 [2–5.25] days, P = 0.211). Rates of haemodialysis (52 vs. 47%; P = 0.680) and transition to extracorporeal membrane oxygenation (13.6 vs. 22.2%; P = 0.521) were comparable. No significant difference was found regarding both 30 day survival (48 vs. 30%; P = 0.126) and in‐hospital mortality (66.7 vs. 74%; P = 0.512), although there was a trend for better survival in the non‐ischaemic group. Conclusions These data suggest that temporary use of the Impella CP device might be a useful therapeutic option for bridge to recovery not only in ischaemic but also in non‐ischaemic cardiogenic shock. KW - Impella KW - Non‐ischaemic cardiogenic shock Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-202794 VL - 6 IS - 4 ER - TY - JOUR A1 - Bekes, Inga A1 - Löb, Sanja A1 - Holzheu, Iris A1 - Janni, Wolfgang A1 - Baumann, Lisa A1 - Wöckel, Achim A1 - Wulff, Christine T1 - Nectin‐2 in ovarian cancer: how is it expressed and what might be its functional role? JF - Cancer Science N2 - Nectin‐2 is an adhesion molecule that has been reported to play a role in tumor growth, metastasis and tumor angiogenesis. Herein, we investigated Nectin‐2 in ovarian cancer patients and in cell culture. Tumor as well as peritoneal biopsies of 60 ovarian cancer patients and 22 controls were dual stained for Nectin‐2 and CD31 using immunohistochemistry. Gene expression of Nectin‐2 was quantified by real‐time PCR and differences analyzed in relation to various tumor characteristics. In the serum of patients, vascular endothelial growth factor (VEGF) was quantified by ELISA. Effect of VEGF on Nectin‐2 expression as well as permeability was investigated in HUVEC. In tumor biopsies, Nectin‐2 protein was mainly localized in tumor cells, whereas in peritoneal biopsies, clear colocalization was found in the vasculature. T3 patients had a significantly higher percentage of positive lymph nodes and this correlated with survival. Nectin‐2 was significantly upregulated in tumor biopsies in patients with lymph node metastasis and with residual tumor >1 cm after surgery. Nectin‐2 expression was significantly suppressed in the peritoneal endothelium of patients associated with significantly increased VEGF serum levels. In cell culture, VEGF stimulation led to a significant downregulation of Nectin‐2 which was reversed by VEGF‐inhibition. In addition, Nectin‐2 knockdown in endothelial cells was associated with significantly increased endothelial permeability. Nectin‐2 expression in ovarian cancer may support tumor cell adhesion, leading to growth and lymph node metastasis. In addition, VEGF‐induced Nectin‐2 suppression in peritoneal endothelium may support an increase in vascular permeability leading to ascites production. KW - metastasis KW - ovarian cancer KW - survival KW - Nectin‐2 KW - VEGF Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-202748 VL - 110 IS - 6 ER - TY - JOUR A1 - Maierhofer, Anna A1 - Flunkert, Julia A1 - Oshima, Junko A1 - Martin, George M. A1 - Poot, Martin A1 - Nanda, Indrajit A1 - Dittrich, Marcus A1 - Müller, Tobias A1 - Haaf, Thomas T1 - Epigenetic signatures of Werner syndrome occur early in life and are distinct from normal epigenetic aging processes JF - Aging Cell N2 - Werner Syndrome (WS) is an adult‐onset segmental progeroid syndrome. Bisulfite pyrosequencing of repetitive DNA families revealed comparable blood DNA methylation levels between classical (18 WRN‐mutant) or atypical WS (3 LMNA‐mutant and 3 POLD1‐mutant) patients and age‐ and sex‐matched controls. WS was not associated with either age‐related accelerated global losses of ALU, LINE1, and α‐satellite DNA methylations or gains of rDNA methylation. Single CpG methylation was analyzed with Infinium MethylationEPIC arrays. In a correspondence analysis, atypical WS samples clustered together with the controls and were clearly separated from classical WS, consistent with distinct epigenetic pathologies. In classical WS, we identified 659 differentially methylated regions (DMRs) comprising 3,656 CpG sites and 613 RefSeq genes. The top DMR was located in the HOXA4 promoter. Additional DMR genes included LMNA, POLD1, and 132 genes which have been reported to be differentially expressed in WRN‐mutant/depleted cells. DMRs were enriched in genes with molecular functions linked to transcription factor activity and sequence‐specific DNA binding to promoters transcribed by RNA polymerase II. We propose that transcriptional misregulation of downstream genes by the absence of WRN protein contributes to the variable premature aging phenotypes of WS. There were no CpG sites showing significant differences in DNA methylation changes with age between WS patients and controls. Genes with both WS‐ and age‐related methylation changes exhibited a constant offset of methylation between WRN‐mutant patients and controls across the entire analyzed age range. WS‐specific epigenetic signatures occur early in life and do not simply reflect an acceleration of normal epigenetic aging processes. KW - (classical and atypical) Werner syndrome KW - bisulfite pyrosequencing KW - methylation array KW - premature aging KW - segmental progeria KW - transcription deficiency Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-202733 VL - 18 ER - TY - JOUR A1 - Beer, Katharina A1 - Schenk, Mariela A1 - Helfrich-Förster, Charlotte A1 - Holzschuh, Andrea T1 - The circadian clock uses different environmental time cues to synchronize emergence and locomotion of the solitary bee Osmia bicornis JF - Scientific Reports N2 - Life on earth adapted to the daily reoccurring changes in environment by evolving an endogenous circadian clock. Although the circadian clock has a crucial impact on survival and behavior of solitary bees, many aspects of solitary bee clock mechanisms remain unknown. Our study is the first to show that the circadian clock governs emergence in Osmia bicornis, a bee species which overwinters as adult inside its cocoon. Therefore, its eclosion from the pupal case is separated by an interjacent diapause from its emergence in spring. We show that this bee species synchronizes its emergence to the morning. The daily rhythms of emergence are triggered by temperature cycles but not by light cycles. In contrast to this, the bee’s daily rhythms in locomotion are synchronized by light cycles. Thus, we show that the circadian clock of O. bicornis is set by either temperature or light, depending on what activity is timed. Light is a valuable cue for setting the circadian clock when bees have left the nest. However, for pre-emerged bees, temperature is the most important cue, which may represent an evolutionary adaptation of the circadian system to the cavity-nesting life style of O. bicornis. KW - Behavioural ecology KW - Evolutionary developmental biology Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-202721 VL - 9 ER - TY - JOUR A1 - Werner, Rudolf A. A1 - Wakabayashi, Hiroshi A1 - Chen, Xinyu A1 - Hayakawa, Nobuyuki A1 - Lapa, Constantin A1 - Rowe, Steven P. A1 - Javadi, Mehrbod S. A1 - Robinson, Simon A1 - Higuchi, Takahiro T1 - Ventricular distribution pattern of the novel sympathetic nerve PET radiotracer \(^{18}\)F-LMI1195 in Rabbit Hearts JF - Scientific Reports N2 - We aimed to determine a detailed regional ventricular distribution pattern of the novel cardiac nerve PET radiotracer \(^{18}\)F-LMI1195 in healthy rabbits. Ex-vivo high resolution autoradiographic imaging was conducted to identify accurate ventricular distribution of \(^{18}\)F-LMI1195. In healthy rabbits, \(^{18}\)F-LMI1195 was administered followed by the reference perfusion marker \(^{201}\)Tl for a dual-radiotracer analysis. After 20 min of \(^{18}\)F-LMI1195 distribution time, the rabbits were euthanized, the hearts were extracted, frozen, and cut into 20-μm short axis slices. Subsequently, the short axis sections were exposed to a phosphor imaging plate to determine \(^{18}\)F-LMI1195 distribution (exposure for 3 h). After complete \(^{18}\)F decay, sections were re-exposed to determine 201Tl distribution (exposure for 7 days). For quantitative analysis, segmental regions of Interest (ROIs) were divided into four left ventricular (LV) and a right ventricular (RV) segment on mid-ventricular short axis sections. Subendocardial, mid-portion, and subepicardial ROIs were placed on the LV lateral wall. \(^{18}\)F-LMI1195 distribution was almost homogeneous throughout the LV wall without any significant differences in all four LV ROIs (anterior, posterior, septal and lateral wall, 99 ± 2, 94 ± 5, 94 ± 4 and 97 ± 3%LV, respectively, n.s.). Subepicardial \(^{201}\)Tl uptake was significantly lower compared to the subendocardial portion (subendocardial, mid-portion, and subepicardial activity: 90 ± 3, 96 ± 2 and *80 ± 5%LV, respectively, *p < 0.01 vs. mid-portion). This was in contradistinction to the transmural wall profile of \(^{18}\)F-LMI1195 (90 ± 4, 96 ± 5 and 84 ± 4%LV, n.s.). A slight but significant discrepant transmural radiotracer distribution pattern of \(^{201}\)Tl in comparison to \(^{18}\)F-LMI1195 may be a reflection of physiological sympathetic innervation and perfusion in rabbit hearts. KW - Cardiovascular diseases KW - Heart failure Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-202707 VL - 9 ER - TY - JOUR A1 - Youssif, Khayrya A. A1 - Haggag, Eman G. A1 - Elshamy, Ali M. A1 - Rabeh, Mohamed A. A1 - Gabr, Nagwan M. A1 - Seleem, Amany A1 - Salem, M. Alaraby A1 - Hussein, Ahmed S. A1 - Krischke, Markus A1 - Mueller, Martin J. A1 - Ramadan Abdelmohsen, Usama T1 - Anti-Alzheimer potential, metabolomic profiling and molecular docking of green synthesized silver nanoparticles of Lampranthus coccineus and Malephora lutea aqueous extracts JF - PLoS ONE N2 - The green synthesis of silver nanoparticles (SNPs) using plant extracts is an eco-friendly method. It is a single step and offers several advantages such as time reducing, cost-effective and environmental non-toxic. Silver nanoparticles are a type of Noble metal nanoparticles and it has tremendous applications in the field of diagnostics, therapeutics, antimicrobial activity, anticancer and neurodegenerative diseases. In the present work, the aqueous extracts of aerial parts of Lampranthus coccineus and Malephora lutea F. Aizoaceae were successfully used for the synthesis of silver nanoparticles. The formation of silver nanoparticles was early detected by a color change from pale yellow to reddish-brown color and was further confirmed by transmission electron microscope (TEM), UV–visible spectroscopy, Fourier transform infrared (FTIR) spectroscopy, dynamic light scattering (DLS), X-ray diffraction (XRD), and energy-dispersive X-ray diffraction (EDX). The TEM analysis of showed spherical nanoparticles with a mean size between 12.86 nm and 28.19 nm and the UV- visible spectroscopy showed λ\(_{max}\) of 417 nm, which confirms the presence of nanoparticles. The neuroprotective potential of SNPs was evaluated by assessing the antioxidant and cholinesterase inhibitory activity. Metabolomic profiling was performed on methanolic extracts of L. coccineus and M. lutea and resulted in the identification of 12 compounds, then docking was performed to investigate the possible interaction between the identified compounds and human acetylcholinesterase, butyrylcholinesterase, and glutathione transferase receptor, which are associated with the progress of Alzheimer’s disease. Overall our SNPs highlighted its promising potential in terms of anticholinesterase and antioxidant activity as plant-based anti-Alzheimer drug and against oxidative stress. KW - Nanoparticles KW - Silver KW - Alzheimer's disease KW - Glutathione KW - Antioxidants KW - Serine proteases KW - Brain diseases KW - Metabolomics Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-202696 VL - 14 IS - 11 ER - TY - JOUR A1 - Wörsdörfer, Philipp A1 - Dalda, Nahide A1 - Kern, Anna A1 - Krüger, Sarah A1 - Wagner, Nicole A1 - Kwok, Chee Keong A1 - Henke, Erik A1 - Ergün, Süleyman T1 - Generation of complex human organoid models including vascular networks by incorporation of mesodermal progenitor cells JF - Scientific Reports N2 - Organoids derived from human pluripotent stem cells are interesting models to study mechanisms of morphogenesis and promising platforms for disease modeling and drug screening. However, they mostly remain incomplete as they lack stroma, tissue resident immune cells and in particular vasculature, which create important niches during development and disease. We propose, that the directed incorporation of mesodermal progenitor cells (MPCs) into organoids will overcome the aforementioned limitations. In order to demonstrate the feasibility of the method, we generated complex human tumor as well as neural organoids. We show that the formed blood vessels display a hierarchic organization and mural cells are assembled into the vessel wall. Moreover, we demonstrate a typical blood vessel ultrastructure including endothelial cell-cell junctions, a basement membrane as well as luminal caveolae and microvesicles. We observe a high plasticity in the endothelial network, which expands, while the organoids grow and is responsive to anti-angiogenic compounds and pro-angiogenic conditions such as hypoxia. We show that vessels within tumor organoids connect to host vessels following transplantation. Remarkably, MPCs also deliver Iba1\(^+\) cells that infiltrate the neural tissue in a microglia-like manner. KW - Developmental biology KW - Stem cells Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-202681 VL - 9 ER - TY - JOUR A1 - Wagner, Fabienne A1 - Kunz, Tobias C. A1 - Chowdhury, Suvagata R. A1 - Thiede, Bernd A1 - Fraunholz, Martin A1 - Eger, Debora A1 - Kozjak-Pavlovic, Vera T1 - Armadillo repeat-containing protein 1 is a dual localization protein associated with mitochondrial intermembrane space bridging complex JF - PLoS ONE N2 - Cristae architecture is important for the function of mitochondria, the organelles that play the central role in many cellular processes. The mitochondrial contact site and cristae organizing system (MICOS) together with the sorting and assembly machinery (SAM) forms the mitochondrial intermembrane space bridging complex (MIB), a large protein complex present in mammalian mitochondria that partakes in the formation and maintenance of cristae. We report here a new subunit of the mammalian MICOS/MIB complex, an armadillo repeat-containing protein 1 (ArmC1). ArmC1 localizes both to cytosol and mitochondria, where it associates with the outer mitochondrial membrane through its carboxy-terminus. ArmC1 interacts with other constituents of the MICOS/MIB complex and its amounts are reduced upon MICOS/MIB complex depletion. Mitochondria lacking ArmC1 do not show defects in cristae structure, respiration or protein content, but appear fragmented and with reduced motility. ArmC1 represents therefore a peripheral MICOS/MIB component that appears to play a role in mitochondrial distribution in the cell. KW - Mitochondria KW - Outer membrane proteins KW - HeLa cells KW - Immunoprecipitation KW - Cytosol KW - Small interfering RNAs KW - Confocal microscopy KW - Cell stainin Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-202670 VL - 14 IS - 10 ER - TY - JOUR A1 - Akhoon, Bashir A. A1 - Gupta, Shishir K. A1 - Tiwari, Sudeep A1 - Rathor, Laxmi A1 - Pant, Aakanksha A1 - Singh, Nivedita A1 - Gupta, Shailendra K. A1 - Dandekar, Thomas A1 - Pandey, Rakesh T1 - C. elegans protein interaction network analysis probes RNAi validated pro-longevity effect of nhr-6, a human homolog of tumor suppressor Nr4a1 JF - Scientific Reports N2 - Protein-protein interaction (PPI) studies are gaining momentum these days due to the plethora of various high-throughput experimental methods available for detecting PPIs. Proteins create complexes and networks by functioning in harmony with other proteins and here in silico network biology hold the promise to reveal new functionality of genes as it is very difficult and laborious to carry out experimental high-throughput genetic screens in living organisms. We demonstrate this approach by computationally screening C. elegans conserved homologs of already reported human tumor suppressor and aging associated genes. We select by this nhr-6, vab-3 and gst-23 as predicted longevity genes for RNAi screen. The RNAi results demonstrated the pro-longevity effect of these genes. Nuclear hormone receptor nhr-6 RNAi inhibition resulted in a C. elegans phenotype of 23.46% lifespan reduction. Moreover, we show that nhr-6 regulates oxidative stress resistance in worms and does not affect the feeding behavior of worms. These findings imply the potential of nhr-6 as a common therapeutic target for aging and cancer ailments, stressing the power of in silico PPI network analysis coupled with RNAi screens to describe gene function. KW - Computer modelling KW - Embryonic induction KW - RNAi Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-202666 VL - 9 ER - TY - JOUR A1 - Schwedhelm, Ivo A1 - Zdzieblo, Daniela A1 - Appelt-Menzel, Antje A1 - Berger, Constantin A1 - Schmitz, Tobias A1 - Schuldt, Bernhard A1 - Franke, Andre A1 - Müller, Franz-Josef A1 - Pless, Ole A1 - Schwarz, Thomas A1 - Wiedemann, Philipp A1 - Walles, Heike A1 - Hansmann, Jan T1 - Automated real-time monitoring of human pluripotent stem cell aggregation in stirred tank reactors JF - Scientific Reports N2 - The culture of human induced pluripotent stem cells (hiPSCs) at large scale becomes feasible with the aid of scalable suspension setups in continuously stirred tank reactors (CSTRs). Innovative monitoring options and emerging automated process control strategies allow for the necessary highly defined culture conditions. Next to standard process characteristics such as oxygen consumption, pH, and metabolite turnover, a reproducible and steady formation of hiPSC aggregates is vital for process scalability. In this regard, we developed a hiPSC-specific suspension culture unit consisting of a fully monitored CSTR system integrated into a custom-designed and fully automated incubator. As a step towards cost-effective hiPSC suspension culture and to pave the way for flexibility at a large scale, we constructed and utilized tailored miniature CSTRs that are largely made from three-dimensional (3D) printed polylactic acid (PLA) filament, which is a low-cost material used in fused deposition modelling. Further, the monitoring tool for hiPSC suspension cultures utilizes in situ microscopic imaging to visualize hiPSC aggregation in real-time to a statistically significant degree while omitting the need for time-intensive sampling. Suitability of our culture unit, especially concerning the developed hiPSC-specific CSTR system, was proven by demonstrating pluripotency of CSTR-cultured hiPSCs at RNA (including PluriTest) and protein level. KW - Biomedical engineering KW - Stem-cell biotechnology Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-202649 VL - 9 ER - TY - JOUR A1 - Liu, Yi A1 - Maierhofer, Tobias A1 - Rybak, Katarzyna A1 - Sklenar, Jan A1 - Breakspear, Andy A1 - Johnston, Matthew G. A1 - Fliegmann, Judith A1 - Huang, Shouguang A1 - Roelfsema, M. Rob G. A1 - Felix, Georg A1 - Faulkner, Christine A1 - Menke, Frank L.H. A1 - Geiger, Dietmar A1 - Hedrich, Rainer A1 - Robatzek, Silke T1 - Anion channel SLAH3 is a regulatory target of chitin receptor-associated kinase PBL27 in microbial stomatal closure JF - eLife N2 - In plants, antimicrobial immune responses involve the cellular release of anions and are responsible for the closure of stomatal pores. Detection of microbe-associated molecular patterns (MAMPs) by pattern recognition receptors (PRRs) induces currents mediated via slow-type (S-type) anion channels by a yet not understood mechanism. Here, we show that stomatal closure to fungal chitin is conferred by the major PRRs for chitin recognition, LYK5 and CERK1, the receptor-like cytoplasmic kinase PBL27, and the SLAH3 anion channel. PBL27 has the capacity to phosphorylate SLAH3, of which S127 and S189 are required to activate SLAH3. Full activation of the channel entails CERK1, depending on PBL27. Importantly, both S127 and S189 residues of SLAH3 are required for chitin-induced stomatal closure and anti-fungal immunity at the whole leaf level. Our results demonstrate a short signal transduction module from MAMP recognition to anion channel activation, and independent of ABA-induced SLAH3 activation. KW - plants Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-202631 VL - 8 ER - TY - JOUR A1 - Jakubietz, Rafael G. A1 - Schmidt, Karsten A1 - Bernuth, Silvia A1 - Meffert, Rainer H. A1 - Jakubietz, Michael G. T1 - Evaluation of the intraoperative blood flow of pedicled perforator flaps using indocyanine green-fluorescence angiography JF - Plastic and Reconstructive Surgery – Global Open N2 - Background: Although indocyanine-green fluorescence angiography (ICG-FA) has been established as a useful tool to assess perfusion in free tissue transfer, only few studies have applied this modality to pedicled perforator flaps. As both volume and reach of pedicled perforator flaps are limited and tip necrosis often equals complete flap failure, ICG-FA may help to detect hypoperfusion in pedicled flaps. Methods: In 5 patients, soft tissue reconstruction was achieved with pedicled perforator flaps. ICG-FA was utilized intraoperatively to visualize flap perfusion. Results: Three pedicled anterolateral thigh flap flaps and 2 propeller flaps were transferred. ICG-FA detected hypoperfusion in 2 flaps. No flap loss occurred; in 2 cases, prolonged wound healing was encountered. Conclusions: ICG-FA confirmed clinical findings and reliably detected tissue areas with hypoperfusion. A clear cut-off point between nonvital tissue and such that stabilized in the following clinical course could not be found. ICG-FA is a promising technology which could also be used in pedicled perforator flaps. KW - surgery Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-202625 VL - 7 IS - 9 ER - TY - JOUR A1 - Lewitzki, Victor A1 - Klement, Rainer J. A1 - Kosmala, Rebekka A1 - Lisowski, Dominik A1 - Flentje, Michael A1 - Polat, Bülent T1 - Accelerated hyperfractionated radiochemotherapy with temozolomide is equivalent to normofractionated radiochemotherapy in a retrospective analysis of patients with glioblastoma JF - Radiation Oncology N2 - Background Current standard of treatment for newly diagnosed patients with glioblastoma (GBM) is surgical resection with adjuvant normofractionated radiotherapy (NFRT) combined with temozolomide (TMZ) chemotherapy. Hyperfractionated accelerated radiotherapy (HFRT) which was known as an option from randomized controlled trials before the temozolomide era has not been compared to the standard therapy in a randomized setting combined with TMZ. Methods Data of 152 patients with newly diagnosed GBM treated from 10/2004 until 7/2018 at a single tertiary care institution were extracted from a clinical database and retrospectively analyzed. Thirty-eight patients treated with NFRT of 60 Gy in 30 fractions (34 with simultaneous and 2 with sequential TMZ) were compared to 114 patients treated with HFRT of 54.0 Gy in 30 fraction of 1.8 Gy twice daily (109 with simultaneous and 3 with sequential TMZ). The association between treatment protocol and other variables with overall survival (OS) was assessed using univariable and multivariable Cox regression analysis; the latter was performed using variables selected by the LASSO method. Results Median overall survival (OS) was 20.3 month for the entire cohort. For patients treated with NFRT median OS was 24.4 months compared to 18.5 months in patients treated with HFRT (p = 0.131). In univariable regression analysis the use of dexamethasone during radiotherapy had a significant negative impact on OS in both patient groups, HR 2.21 (95% CI 1.47–3.31, p = 0.0001). In multivariable analysis adjusted for O6-methylguanine-DNA methyl-transferase (MGMT) promotor methylation status, salvage treatment and secondary GBM, the use of dexamethasone was still a negative prognostic factor, HR 1.95 (95% CI 1.21–3.13, p = 0.006). Positive MGMT-methylation status and salvage treatment were highly significant positive prognostic factors. There was no strong association between treatment protocol and OS (p = 0.504). Conclusions Our retrospective analysis supports the hypothesis of equivalence between HFRT and the standard protocol of treatment for GBM. For those patients who are willing to obtain the benefit of shortening the course of radiochemotherapy, HFRT may be an alternative with comparable efficacy although it was not yet tested in a large prospective randomized study against the current standard. The positive influence of salvage therapy and negative impact of concomitant use of corticosteroids should be addressed in future prospective trials. To confirm our results, we plan to perform a pooled analysis with other tertiary clinics in order to achieve better statistical reliability. KW - Brain cancer KW - Glioblastoma KW - High grade glioma KW - Radiotherapy KW - Temozolomide KW - Corticosteroids Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-202614 VL - 14 ER - TY - JOUR A1 - Kehrberger, Sandra A1 - Holzschuh, Andrea T1 - How does timing of flowering affect competition for pollinators, flower visitation and seed set in an early spring grassland plant? JF - Scientific Reports N2 - Knowledge on how the timing of flowering is related to plant fitness and species interactions is crucial to understand consequences of phenological shifts as they occur under climate change. Early flowering plants may face advantages of low competition for pollinators and disadvantages of low pollinator abundances and unfavourable weather conditions. However, it is unknown how this trade-off changes over the season and how the timing affects reproductive success. On eight grasslands we recorded intra-seasonal changes in pollinators, co-flowering plants, weather conditions, flower visitation rates, floral longevity and seed set of Pulsatilla vulgaris. Although bee abundances and the number of pollinator-suitable hours were low at the beginning of the season, early flowers of P. vulgaris received higher flower visitation rates and estimated total number of bee visits than later flowers, which was positively related to seed set. Flower visitation rates decreased over time and with increasing number of co-flowering plants, which competed with P. vulgaris for pollinators. Low interspecific competition for pollinators seems to be a major driver for early flowering dates. Thus, non-synchronous temporal shifts of co-flowering plants as they may occur under climate warming can be expected to strongly affect plant-pollinator interactions and the fitness of the involved plants. KW - ecology Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-202549 VL - 9 ER - TY - JOUR A1 - Heiby, Julia C. A1 - Goretzki, Benedikt A1 - Johnson, Christopher M. A1 - Hellmich, Ute A. A1 - Neuweiler, Hannes T1 - Methionine in a protein hydrophobic core drives tight interactions required for assembly of spider silk JF - Nature Communications N2 - Web spiders connect silk proteins, so-called spidroins, into fibers of extraordinary toughness. The spidroin N-terminal domain (NTD) plays a pivotal role in this process: it polymerizes spidroins through a complex mechanism of dimerization. Here we analyze sequences of spidroin NTDs and find an unusually high content of the amino acid methionine. We simultaneously mutate all methionines present in the hydrophobic core of a spidroin NTD from a nursery web spider’s dragline silk to leucine. The mutated NTD is strongly stabilized and folds at the theoretical speed limit. The structure of the mutant is preserved, yet its ability to dimerize is substantially impaired. We find that side chains of core methionines serve to mobilize the fold, which can thereby access various conformations and adapt the association interface for tight binding. Methionine in a hydrophobic core equips a protein with the capacity to dynamically change shape and thus to optimize its function. KW - Circular dichroism KW - Fluorescence spectroscopy KW - Protein folding KW - Solution-state NMR Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-202539 VL - 10 ER - TY - JOUR A1 - Vogel, Patrick A1 - Markert, Jonathan A1 - Rückert, Martin A. A1 - Herz, Stefan A1 - Keßler, Benedikt A1 - Dremel, Kilian A1 - Althoff, Daniel A1 - Weber, Matthias A1 - Buzug, Thorsten M. A1 - Bley, Thorsten A. A1 - Kullmann, Walter H. A1 - Hanke, Randolf A1 - Zabler, Simon A1 - Behr, Volker C. T1 - Magnetic Particle Imaging meets computed tomography: first simultaneous imaging JF - Scientific Reports N2 - Magnetic Particle Imaging (MPI) is a promising new tomographic modality for fast as well as three-dimensional visualization of magnetic material. For anatomical or structural information an additional imaging modality such as computed tomography (CT) is required. In this paper, the first hybrid MPI-CT scanner for multimodal imaging providing simultaneous data acquisition is presented. KW - Applied physics KW - Biomedical engineering KW - Imaging techniques Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-202501 VL - 9 ER - TY - JOUR A1 - Müller-Scholden, Lara A1 - Kirchhof, Jan A1 - Morbach, Caroline A1 - Breunig, Margret A1 - Meijer, Rudy A1 - Rücker, Viktoria A1 - Tiffe, Theresa A1 - Yurdadogan, Tino A1 - Wagner, Martin A1 - Gelbrich, Götz A1 - Bots, Michiel L. A1 - Störk, Stefan A1 - Heuschmann, Peter U. T1 - Segment-specific association of carotid-intima-media thickness with cardiovascular risk factors – findings from the STAAB cohort study JF - BMC Cardiovascular Disorders N2 - Background The guideline recommendation to not measure carotid intima-media thickness (CIMT) for cardiovascular risk prediction is based on the assessment of just one single carotid segment. We evaluated whether there is a segment-specific association between different measurement locations of CIMT and cardiovascular risk factors. Methods Subjects from the population-based STAAB cohort study comprising subjects aged 30 to 79 years of the general population from Würzburg, Germany, were investigated. CIMT was measured on the far wall of both sides in three different predefined locations: common carotid artery (CCA), bulb, and internal carotid artery (ICA). Diabetes, dyslipidemia, hypertension, smoking, and obesity were considered as risk factors. In multivariable logistic regression analysis, odds ratios of risk factors per location were estimated for the endpoint of individual age- and sex-adjusted 75th percentile of CIMT. Results 2492 subjects were included in the analysis. Segment-specific CIMT was highest in the bulb, followed by CCA, and lowest in the ICA. Dyslipidemia, hypertension, and smoking were associated with CIMT, but not diabetes and obesity. We observed no relevant segment-specific association between the three different locations and risk factors, except for a possible interaction between smoking and ICA. Conclusions As no segment-specific association between cardiovascular risk factors and CIMT became evident, one simple measurement of one location may suffice to assess the cardiovascular risk of an individual. KW - Carotid intima-media thickness (CIMT) KW - Carotid segment KW - Carotid ultrasound KW - Cardiovascular risk factors KW - Cardiovascular risk prediction Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-200720 VL - 19 IS - 84 ER - TY - JOUR A1 - Silwedel, Christine A1 - Haarmann, Axel A1 - Fehrholz, Markus A1 - Claus, Heike A1 - Speer, Christian P. A1 - Glaser, Kirsten T1 - More than just inflammation: Ureaplasma species induce apoptosis in human brain microvascular endothelial cells JF - Journal of Neuroinflammation N2 - Background Ureaplasma species (spp.) are commonly regarded as low-virulent commensals but may cause invasive diseases in immunocompromised adults and in neonates, including neonatal meningitis. The interactions of Ureaplasma spp. with host defense mechanisms are poorly understood. This study addressed Ureaplasma-driven cell death, concentrating on apoptosis as well as inflammatory cell death. Methods Human brain microvascular endothelial cells (HBMEC) were exposed to Ureaplasma (U.) urealyticum serovar 8 (Uu8) and U. parvum serovar 3 (Up3). Resulting numbers of dead cells as well as mRNA levels and enzyme activity of key agents in programmed cell death were assessed by flow cytometry, RNA sequencing, and qRT-PCR, respectively. xCELLigence data were used for real-time monitoring of changes in cell adhesion properties. Results Both Ureaplasma isolates induced cell death (p < 0.05, vs. broth). Furthermore, Ureaplasma spp. enhanced mRNA levels for genes in apoptosis, including caspase 3 (Up3 p < 0.05, vs. broth), caspase 7 (p < 0.01), and caspase 9 (Up3 p < 0.01). Caspase 3 activity was increased upon Uu8 exposure (p < 0.01). Vice versa, Ureaplasma isolates downregulated mRNA levels for proteins involved in inflammatory cell death, namely caspase 1 (Uu8 p < 0.01, Up3 p < 0.001), caspase 4 (Uu8 p < 0.05, Up3 p < 0.01), NOD-like receptor pyrin domain-containing 3 (Uu8 p < 0.05), and receptor-interacting protein kinase 3 (p < 0.05). Conclusions By inducing apoptosis in HBMEC as main constituents of the blood-brain barrier, Ureaplasma spp. may provoke barrier breakdown. Simultaneous suppression of inflammatory cell death may additionally attenuate host defense strategies. Ultimate consequence could be invasive and long-term CNS infections by Ureaplasma spp. KW - Ureaplasma urealyticum KW - Ureaplasma parvum KW - Neuroinflammation KW - Meningitis KW - Caspase KW - Apoptosis KW - HBMEC Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-200711 VL - 16 ER - TY - JOUR A1 - Mueller, Stefan A1 - Lüttig, Julian A1 - Malý, Pavel A1 - Ji, Lei A1 - Han, Jie A1 - Moos, Michael A1 - Marder, Todd B. A1 - Bunz, Uwe H. F. A1 - Dreuw, Andreas A1 - Lambert, Christoph A1 - Brixner, Tobias T1 - Rapid multiple-quantum three-dimensional fluorescence spectroscopy disentangles quantum pathways JF - Nature Communications N2 - Coherent two-dimensional spectroscopy is a powerful tool for probing ultrafast quantum dynamics in complex systems. Several variants offer different types of information but typically require distinct beam geometries. Here we introduce population-based three-dimensional (3D) electronic spectroscopy and demonstrate the extraction of all fourth- and multiple sixth-order nonlinear signal contributions by employing 125-fold (1⨯5⨯5⨯5) phase cycling of a four-pulse sequence. Utilizing fluorescence detection and shot-to-shot pulse shaping in single-beam geometry, we obtain various 3D spectra of the dianion of TIPS-tetraazapentacene, a fluorophore with limited stability at ambient conditions. From this, we recover previously unknown characteristics of its electronic two-photon state. Rephasing and nonrephasing sixth-order contributions are measured without additional phasing that hampered previous attempts using noncollinear geometries. We systematically resolve all nonlinear signals from the same dataset that can be acquired in 8 min. The approach is generalizable to other incoherent observables such as external photoelectrons, photocurrents, or photoions. KW - Atomic and molecular interactions with photons KW - Optical spectroscopy Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-202529 VL - 10 ER - TY - JOUR A1 - Dechaud, Corentin A1 - Volff, Jean-Nicolas A1 - Schartl, Manfred A1 - Naville, Magali T1 - Sex and the TEs: transposable elements in sexual development and function in animals JF - Mobile DNA N2 - Transposable elements are endogenous DNA sequences able to integrate into and multiply within genomes. They constitute a major source of genetic innovations, as they can not only rearrange genomes but also spread ready-to-use regulatory sequences able to modify host gene expression, and even can give birth to new host genes. As their evolutionary success depends on their vertical transmission, transposable elements are intrinsically linked to reproduction. In organisms with sexual reproduction, this implies that transposable elements have to manifest their transpositional activity in germ cells or their progenitors. The control of sexual development and function can be very versatile, and several studies have demonstrated the implication of transposable elements in the evolution of sex. In this review, we report the functional and evolutionary relationships between transposable elements and sexual reproduction in animals. In particular, we highlight how transposable elements can influence expression of sexual development genes, and how, reciprocally, they are tightly controlled in gonads. We also review how transposable elements contribute to the organization, expression and evolution of sexual development genes and sex chromosomes. This underscores the intricate co-evolution between host functions and transposable elements, which regularly shift from a parasitic to a domesticated status useful to the host. KW - Transposable element KW - Sex determination KW - Sexual development and function KW - Germline KW - piRNA KW - Sex chromosome Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-202510 VL - 10 ER - TY - JOUR A1 - Lopez-Arreguin, A. J. R. A1 - Montenegro, S. T1 - Improving engineering models of terramechanics for planetary exploration JF - Results in Engineering N2 - This short letter proposes more consolidated explicit solutions for the forces and torques acting on typical rover wheels, that can be used as a method to determine their average mobility characteristics in planetary soils. The closed loop solutions stand in one of the verified methods, but at difference of the previous, observables are decoupled requiring a less amount of physical parameters to measure. As a result, we show that with knowledge of terrain properties, wheel driving performance rely in a single observable only. Because of their generality, the formulated equations established here can have further implications in autonomy and control of rovers or planetary soil characterization. KW - Wheel KW - Terramechanics KW - Forces KW - Torque KW - Robotics Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-202490 VL - 3 ER - TY - JOUR A1 - Krebs, Markus A1 - Behrmann, Christoph A1 - Kalogirou, Charis A1 - Sokolakis, Ioannis A1 - Kneitz, Susanne A1 - Kruithof-de Julio, Marianna A1 - Zoni, Eugenio A1 - Rech, Anne A1 - Schilling, Bastian A1 - Kübler, Hubert A1 - Spahn, Martin A1 - Kneitz, Burkhard T1 - miR-221 Augments TRAIL-mediated apoptosis in prostate cancer cells by inducing endogenous TRAIL expression and targeting the functional repressors SOCS3 and PIK3R1 JF - BioMed Research International N2 - miR-221 is regarded as an oncogene in many malignancies, and miR-221-mediated resistance towards TRAIL was one of the first oncogenic roles shown for this small noncoding RNA. In contrast, miR-221 is downregulated in prostate cancer (PCa), thereby implying a tumour suppressive function. By using proliferation and apoptosis assays, we show a novel feature of miR-221 in PCa cells: instead of inducing TRAIL resistance, miR-221 sensitized cells towards TRAIL-induced proliferation inhibition and apoptosis induction. Partially responsible for this effect was the interferon-mediated gene signature, which among other things contained an endogenous overexpression of the TRAIL encoding gene TNFSF10. This TRAIL-friendly environment was provoked by downregulation of the established miR-221 target gene SOCS3. Moreover, we introduced PIK3R1 as a target gene of miR-221 in PCa cells. Proliferation assays showed that siRNA-mediated downregulation of SOCS3 and PIK3R1 mimicked the effect of miR-221 on TRAIL sensitivity. Finally, Western blotting experiments confirmed lower amounts of phospho-Akt after siRNA-mediated downregulation of PIK3R1 in PC3 cells. Our results further support the tumour suppressing role of miR-221 in PCa, since it sensitises PCa cells towards TRAIL by regulating the expression of the oncogenes SOCS3 and PIK3R1. Given the TRAIL-inhibiting effect of miR-221 in various cancer entities, our results suggest that the influence of miR-221 on TRAIL-mediated apoptosis is highly context- and entity-dependent. KW - Cancer Cell Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-202480 VL - 2019 ER - TY - JOUR A1 - Herz, Michaela A1 - Brehm, Klaus T1 - Evidence for densovirus integrations into tapeworm genomes JF - Parasites & Vectors N2 - Background Tapeworms lack a canonical piRNA-pathway, raising the question of how they can silence existing mobile genetic elements (MGE). Investigation towards the underlying mechanisms requires information on tapeworm transposons which is, however, presently scarce. Methods The presence of densovirus-related sequences in tapeworm genomes was studied by bioinformatic approaches. Available RNA-Seq datasets were mapped against the Echinococcus multilocularis genome to calculate expression levels of densovirus-related genes. Transcription of densovirus loci was further analyzed by sequencing and RT-qPCR. Results We herein provide evidence for the presence of densovirus-related elements in a variety of tapeworm genomes. In the high-quality genome of E. multilocularis we identified more than 20 individual densovirus integration loci which contain the information for non-structural and structural virus proteins. The majority of densovirus loci are present as head-to-tail concatemers in isolated repeat containing regions of the genome. In some cases, unique densovirus loci have integrated close to histone gene clusters. We show that some of the densovirus loci of E. multilocularis are actively transcribed, whereas the majority are transcriptionally silent. RT-qPCR data further indicate that densovirus expression mainly occurs in the E. multilocularis stem cell population, which probably forms the germline of this organism. Sequences similar to the non-structural densovirus genes present in E. multilocularis were also identified in the genomes of E. canadensis, E. granulosus, Hydatigera taeniaeformis, Hymenolepis diminuta, Hymenolepis microstoma, Hymenolepis nana, Taenia asiatica, Taenia multiceps, Taenia saginata and Taenia solium. Conclusions Our data indicate that densovirus integration has occurred in many tapeworm species. This is the first report on widespread integration of DNA viruses into cestode genomes. Since only few densovirus integration sites were transcriptionally active in E. multilocularis, our data are relevant for future studies into gene silencing mechanisms in tapeworms. Furthermore, they indicate that densovirus-based vectors might be suitable tools for genetic manipulation of cestodes. KW - Echinococcus KW - Echinococcosis KW - Densovirus KW - Parvovirus KW - Mobile genetic element KW - Gene silencing KW - Stem cell KW - Epigenetic Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-202478 VL - 12 ER -