TY - JOUR A1 - Appel, Markus A1 - Marker, Caroline A1 - Mara, Martina T1 - Otakuism and the appeal of sex robots JF - Frontiers in Psychology N2 - Social robots are becoming increasingly prevalent in everyday life and sex robots are a sub-category of especially high public interest and controversy. Starting from the concept of the otaku, a term from Japanese youth culture that describes secluded persons with a high affinity for fictional manga characters, we examine individual differences behind sex robot appeal (anime and manga fandom, interest in Japanese culture, preference for indoor activities, shyness). In an online-experiment, 261 participants read one out of three randomly assigned descriptions of future technologies (sex robot, nursing robot, genetically modified organism) and reported on their overall evaluation, eeriness, and contact/purchase intentions. Higher anime and manga fandom was associated with higher appeal for all three future technologies. For our male subsample, sex robots and GMOs stood out as shyness yielded a particularly strong relationship to contact/purchase intentions for these new technologies. KW - sex robots KW - anime KW - manga KW - fan culture KW - otakuism KW - shyness KW - uncanny valley Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-195893 SN - 1664-1078 VL - 10 IS - 569 ER - TY - JOUR A1 - Reul, Christian A1 - Christ, Dennis A1 - Hartelt, Alexander A1 - Balbach, Nico A1 - Wehner, Maximilian A1 - Springmann, Uwe A1 - Wick, Christoph A1 - Grundig, Christine A1 - Büttner, Andreas A1 - Puppe, Frank T1 - OCR4all—An open-source tool providing a (semi-)automatic OCR workflow for historical printings JF - Applied Sciences N2 - Optical Character Recognition (OCR) on historical printings is a challenging task mainly due to the complexity of the layout and the highly variant typography. Nevertheless, in the last few years, great progress has been made in the area of historical OCR, resulting in several powerful open-source tools for preprocessing, layout analysis and segmentation, character recognition, and post-processing. The drawback of these tools often is their limited applicability by non-technical users like humanist scholars and in particular the combined use of several tools in a workflow. In this paper, we present an open-source OCR software called OCR4all, which combines state-of-the-art OCR components and continuous model training into a comprehensive workflow. While a variety of materials can already be processed fully automatically, books with more complex layouts require manual intervention by the users. This is mostly due to the fact that the required ground truth for training stronger mixed models (for segmentation, as well as text recognition) is not available, yet, neither in the desired quantity nor quality. To deal with this issue in the short run, OCR4all offers a comfortable GUI that allows error corrections not only in the final output, but already in early stages to minimize error propagations. In the long run, this constant manual correction produces large quantities of valuable, high quality training material, which can be used to improve fully automatic approaches. Further on, extensive configuration capabilities are provided to set the degree of automation of the workflow and to make adaptations to the carefully selected default parameters for specific printings, if necessary. During experiments, the fully automated application on 19th Century novels showed that OCR4all can considerably outperform the commercial state-of-the-art tool ABBYY Finereader on moderate layouts if suitably pretrained mixed OCR models are available. Furthermore, on very complex early printed books, even users with minimal or no experience were able to capture the text with manageable effort and great quality, achieving excellent Character Error Rates (CERs) below 0.5%. The architecture of OCR4all allows the easy integration (or substitution) of newly developed tools for its main components by standardized interfaces like PageXML, thus aiming at continual higher automation for historical printings. KW - optical character recognition KW - document analysis KW - historical printings Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-193103 SN - 2076-3417 VL - 9 IS - 22 ER - TY - JOUR A1 - Duan, Xiaodong A1 - Nagel, Georg A1 - Gao, Shiqiang T1 - Mutated channelrhodopsins with increased sodium and calcium permeability JF - Applied Sciences N2 - (1) Background: After the discovery and application of Chlamydomonas reinhardtii channelrhodopsins, the optogenetic toolbox has been greatly expanded with engineered and newly discovered natural channelrhodopsins. However, channelrhodopsins of higher Ca\(^{2+}\) conductance or more specific ion permeability are in demand. (2) Methods: In this study, we mutated the conserved aspartate of the transmembrane helix 4 (TM4) within Chronos and PsChR and compared them with published ChR2 aspartate mutants. (3) Results: We found that the ChR2 D156H mutant (XXM) showed enhanced Na\(^+\) and Ca\(^{2+}\) conductance, which was not noticed before, while the D156C mutation (XXL) influenced the Na\(^+\) and Ca\(^{2+}\) conductance only slightly. The aspartate to histidine and cysteine mutations of Chronos and PsChR also influenced their photocurrent, ion permeability, kinetics, and light sensitivity. Most interestingly, PsChR D139H showed a much-improved photocurrent, compared to wild type, and even higher Na+ selectivity to H\(^+\) than XXM. PsChR D139H also showed a strongly enhanced Ca\(^{2+}\) conductance, more than two-fold that of the CatCh. (4) Conclusions: We found that mutating the aspartate of the TM4 influences the ion selectivity of channelrhodopsins. With the large photocurrent and enhanced Na\(^+\) selectivity and Ca\(^{2+}\) conductance, XXM and PsChR D139H are promising powerful optogenetic tools, especially for Ca\(^{2+}\) manipulation. KW - optogenetics KW - channelrhodopsins KW - sodium KW - calcium KW - DC gate Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-197435 SN - 2076-3417 VL - 9 IS - 4 ER - TY - JOUR A1 - Wallmann-Sperlich, Birgit A1 - Hoffmann, Sophie A1 - Salditt, Anne A1 - Bipp, Tanja A1 - Froboese, Ingo T1 - Moving to an “active” biophilic designed office workplace: a pilot study about the effects on sitting time and sitting habits of office-based workers JF - International Journal of Environmental Research and Public Health N2 - Promising initial insights show that offices designed to permit physical activity (PA) may reduce workplace sitting time. Biophilic approaches are intended to introduce natural surroundings into the workplace, and preliminary data show positive effects on stress reduction and elevated productivity within the workplace. The primary aim of this pilot study was to analyze changes in workplace sitting time and self-reported habit strength concerning uninterrupted sitting and PA during work, when relocating from a traditional office setting to “active” biophilic-designed surroundings. The secondary aim was to assess possible changes in work-associated factors such as satisfaction with the office environment, work engagement, and work performance, among office staff. In a pre-post designed field study, we collected data through an online survey on health behavior at work. Twelve participants completed the survey before (one-month pre-relocation, T1) and twice after the office relocation (three months (T2) and seven months post-relocation (T3)). Standing time per day during office hours increased from T1 to T3 by about 40 min per day (p < 0.01). Other outcomes remained unaltered. The results suggest that changing office surroundings to an active-permissive biophilic design increased standing time during working hours. Future larger-scale controlled studies are warranted to investigate the influence of office design on sitting time and work-associated factors during working hours in depth. KW - desk-based KW - office-workers KW - standing KW - online survey KW - walking KW - work engagement KW - habit strength KW - work performance KW - office environment Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-197371 SN - 1660-4601 VL - 16 IS - 9 ER - TY - JOUR A1 - Djebko, Kirill A1 - Puppe, Frank A1 - Kayal, Hakan T1 - Model-based fault detection and diagnosis for spacecraft with an application for the SONATE triple cube nano-satellite JF - Aerospace N2 - The correct behavior of spacecraft components is the foundation of unhindered mission operation. However, no technical system is free of wear and degradation. A malfunction of one single component might significantly alter the behavior of the whole spacecraft and may even lead to a complete mission failure. Therefore, abnormal component behavior must be detected early in order to be able to perform counter measures. A dedicated fault detection system can be employed, as opposed to classical health monitoring, performed by human operators, to decrease the response time to a malfunction. In this paper, we present a generic model-based diagnosis system, which detects faults by analyzing the spacecraft’s housekeeping data. The observed behavior of the spacecraft components, given by the housekeeping data is compared to their expected behavior, obtained through simulation. Each discrepancy between the observed and the expected behavior of a component generates a so-called symptom. Given the symptoms, the diagnoses are derived by computing sets of components whose malfunction might cause the observed discrepancies. We demonstrate the applicability of the diagnosis system by using modified housekeeping data of the qualification model of an actual spacecraft and outline the advantages and drawbacks of our approach. KW - fault detection KW - model-based diagnosis KW - nano-satellite Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-198836 SN - 2226-4310 VL - 6 IS - 10 ER - TY - JOUR A1 - Elmaidomy, Abeer H. A1 - Mohammed, Rabab A1 - Hassan, Hossam M. A1 - Owis, Asmaa I. A1 - Rateb, Mostafa E. A1 - Khanfar, Mohammad A. A1 - Krischke, Markus A1 - Mueller, Martin J. A1 - Abdelmohsen, Usama Ramadan T1 - Metabolomic profiling and cytotoxic tetrahydrofurofuran lignans investigations from Premna odorata Blanco JF - Metabolites N2 - Metabolomic profiling of different Premna odorata Blanco (Lamiaceae) organs, bark, wood, young stems, flowers, and fruits dereplicated 20, 20, 10, 20, and 20 compounds, respectively, using LC–HRESIMS. The identified metabolites (1–34) belonged to different chemical classes, including iridoids, flavones, phenyl ethanoids, and lignans. A phytochemical investigation of P. odorata bark afforded one new tetrahydrofurofuran lignan, 4β-hydroxyasarinin 35, along with fourteen known compounds. The structure of the new compound was confirmed using extensive 1D and 2D NMR, and HRESIMS analyses. A cytotoxic investigation of compounds 35–38 against the HL-60, HT-29, and MCF-7 cancer cell lines, using the MTT assay showed that compound 35 had cytotoxic effects against HL-60 and MCF-7 with IC50 values of 2.7 and 4.2 µg/mL, respectively. A pharmacophore map of compounds 35 showed two hydrogen bond acceptor (HBA) aligning the phenoxy oxygen atoms of benzodioxole moieties, two aromatic ring features vectored on the two phenyl rings, one hydrogen bond donor (HBD) feature aligning the central hydroxyl group and thirteen exclusion spheres which limit the boundaries of sterically inaccessible regions of the target’s active site. KW - Premna KW - lignan KW - metabolomic KW - cytotoxic KW - pharmacophore map Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-193187 SN - 2218-1989 VL - 9 IS - 10 ER - TY - JOUR A1 - Tiwarekar, Vishakha A1 - Fehrholz, Markus A1 - Schneider-Schaulies, Jürgen T1 - KDELR2 competes with measles virus envelope proteins for cellular chaperones reducing their chaperone-mediated cell surface transport JF - Viruses N2 - Recently, we found that the cytidine deaminase APOBEC3G (A3G) inhibits measles (MV) replication. Using a microarray, we identified differential regulation of several host genes upon ectopic expression of A3G. One of the up-regulated genes, the endoplasmic reticulum (ER) protein retention receptor KDELR2, reduced MV replication ~5 fold when it was over-expressed individually in Vero and CEM-SS T cells. Silencing of KDELR2 in A3G-expressing Vero cells abrogated the antiviral activity induced by A3G, confirming its role as an A3G-regulated antiviral host factor. Recognition of the KDEL (Lys-Asp-Glu-Leu) motif by KDEL receptors initiates the retrograde transport of soluble proteins that have escaped the ER and play an important role in ER quality control. Although KDELR2 over-expression reduced MV titers in cell cultures, we observed no interaction between KDELR2 and the MV hemagglutinin (H) protein. Instead, KDELR2 retained chaperones in the ER, which are required for the correct folding and transport of the MV envelope glycoproteins H and fusion protein (F) to the cell surface. Our data indicate that KDELR2 competes with MV envelope proteins for binding to calnexin and GRP78/Bip, and that this interaction limits the availability of the chaperones for MV proteins, causing the reduction of virus spread and titers. KW - measles virus KW - KDELR2 KW - calnexin KW - GRP78 KW - surface transport Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-197468 SN - 1999-4915 VL - 11 IS - 1 ER - TY - JOUR A1 - Menke, Andreas T1 - Is the HPA axis as target for depression outdated, or is there a new hope? JF - Frontiers in Psychiatry N2 - Major depressive disorder (MDD) is a very common stress-related mental disorder that carries a huge burden for affected patients and the society. It is associated with a high mortality that derives from suicidality and the development of serious medical conditions such as heart diseases, diabetes, and stroke. Although a range of effective antidepressants are available, more than 50% of the patients do not respond to the first treatment they are prescribed and around 30% fail to respond even after several treatment attempts. The heterogeneous condition of MDD, the lack of biomarkers matching patients with the right treatments and the situation that almost all available drugs are only targeting the serotonin, norepinephrine, or dopamine signaling, without regulating other potentially dysregulated systems may explain the insufficient treatment status. The hypothalamic-pituitary-adrenal (HPA) axis is one of these other systems, there is numerous and robust evidence that it is implicated in MDD and other stress-related conditions, but up to date there is no specific drug targeting HPA axis components that is approved and no test that is routinely used in the clinical setting identifying patients for such a specific treatment. Is there still hope after these many years for a breakthrough of agents targeting the HPA axis? This review will cover tests detecting altered HPA axis function and the specific treatment options such as glucocorticoid receptor (GR) antagonists, corticotropin-releasing hormone 1 (CRH1) receptor antagonists, tryptophan 2,3-dioxygenase (TDO) inhibitors and FK506 binding protein 5 (FKBP5) receptor antagonists. KW - precision medicine KW - personalized medicine KW - biomarker KW - depression KW - HPA axis KW - glucocorticoid receptor KW - CRH1 KW - FKBP5 Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-195780 SN - 1664-0640 VL - 10 IS - 101 ER - TY - JOUR A1 - Odorfer, Thorsten M. A1 - Homola, György A. A1 - Reich, Martin M. A1 - Volkmann, Jens A1 - Zeller, Daniel T1 - Increased finger-tapping related cerebellar activation in cervical dystonia, enhanced by transcranial stimulation: an indicator of compensation? JF - Frontiers in Neurology N2 - Background: Cervical dystonia is a movement disorder causing abnormal postures and movements of the head. While the exact pathophysiology of cervical dystonia has not yet been fully elucidated, a growing body of evidence points to the cerebellum as an important node. Methods: Here, we examined the impact of cerebellar interference by transcranial magnetic stimulation on finger-tapping related brain activation and neurophysiological measures of cortical excitability and inhibition in cervical dystonia and controls. Bilateral continuous theta-burst stimulation was used to modulate cerebellar cortical excitability in 16 patients and matched healthy controls. In a functional magnetic resonance imaging arm, data were acquired during simple finger tapping before and after cerebellar stimulation. In a neurophysiological arm, assessment comprised motor-evoked potentials amplitude and cortical silent period duration. Theta-burst stimulation over the dorsal premotor cortex and sham stimulation (neurophysiological arm only) served as control conditions. Results: At baseline, finger tapping was associated with increased activation in the ipsilateral cerebellum in patients compared to controls. Following cerebellar theta-burst stimulation, this pattern was even more pronounced, along with an additional movement-related activation in the contralateral somatosensory region and angular gyrus. Baseline motor-evoked potential amplitudes were higher and cortical silent period duration shorter in patients compared to controls. After cerebellar theta-burst stimulation, cortical silent period duration increased significantly in dystonia patients. Conclusion: We conclude that in cervical dystonia, finger movements—though clinically non-dystonic—are associated with increased activation of the lateral cerebellum, possibly pointing to general motor disorganization, which remains subclinical in most body regions. Enhancement of this activation together with an increase of silent period duration by cerebellar continuous theta-burst stimulation may indicate predominant disinhibitory effects on Purkinje cells, eventually resulting in an inhibition of cerebello-thalamocortical circuits. KW - cervical dystonia KW - functional MRI KW - cortical excitability KW - transcranial magnetic simulation (TMS) KW - continuous theta burst stimulation (cTBS) KW - motor-evoked potentials (MEP) KW - cortical silent period Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-196249 SN - 1664-2295 VL - 10 IS - 231 ER - TY - JOUR A1 - Weber, Silvana A1 - Lorenz, Christopher A1 - Hemmings, Nicola T1 - Improving stress and positive mental health at work via an app-based intervention: a large-scale multi-center randomized control trial JF - Frontiers in Psychology N2 - Mobile health interventions (i.e., “apps”) are used to address mental health and are an increasingly popular method available to both individuals and organizations to manage workplace stress. However, at present, there is a lack of research on the effectiveness of mobile health interventions in counteracting or improving stress-related health problems, particularly in naturalistic, non-clinical settings. This project aimed at validating a mobile health intervention (which is theoretically grounded in the Job Demands-Resources Model) in preventing and managing stress at work. Within the mobile health intervention, employees make an evidence-based, personalized, psycho-educational journey to build further resources, and thus, reduce stress. A large-scale longitudinal randomized control trial, conducted with six European companies over 6 weeks using four measurement points, examined indicators of mental health via measures of stress, wellbeing, resilience, and sleep. The data were analyzed by means of hierarchical multilevel models for repeated measures, including both self-report measures and user behavior metrics from the app. The results (n = 532) suggest that using the mobile health intervention (vs. waitlist control group) significantly improved stress and wellbeing over time. Higher engagement in the intervention increased the beneficial effects. Additionally, use of the sleep tracking function led to an improvement in sleeping troubles. The intervention had no effects on measures of physical health or social community at work. Theoretical and practical implications of these findings are discussed, focusing on benefits and challenges of using technological solutions for organizations to support individuals’ mental health in the workplace. KW - stress KW - work KW - RCT KW - mental health KW - digital health KW - mobile health intervention KW - smartphone app Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-194337 SN - 1664-1078 VL - 10 IS - 2745 ER - TY - JOUR A1 - Belka, Janina A1 - Nickel, Joachim A1 - Kurth, Dirk G. T1 - Growth on metallo-supramolecular coordination polyelectrolyte (MEPE) stimulates osteogenic differentiation of human osteosarcoma cells (MG63) and human bone marrow derived mesenchymal stem cells JF - Polymers N2 - Background: Culturing of cells is typically performed on standard tissue culture plates generating growth conditions, which in general do not reflect the native three-dimensional cellular environment. Recent investigations provide insights in parameters, which strongly affect the general cellular behavior triggering essential processes such as cell differentiation. The physical properties of the used material, such as stiffness, roughness, or topology, as well as the chemical composition of the cell-surface interface are shown to play a key role in the initiation of particular cellular responses. Methods: We extended our previous research, which identified thin films of metallo-supramolecular coordination polyelectrolytes (MEPEs) as substrate to trigger the differentiation of muscular precursor cells. Results: Here, we show that the same MEPEs similarly stimulate the osteogenic differentiation of pre-osteoblasts. Remarkably, MEPE modified surfaces also trigger the differentiation of primary bone derived mesenchymal stem cells (BMSCs) towards the osteogenic lineage. Conclusion: This result leads to the conclusion that these surfaces individually support the specification of cell differentiation toward lineages that correspond to the natural commitment of the particular cell types. We, therefore, propose that Fe-MEPEs may be used as scaffold for the treatment of defects at least in muscular or bone tissue. KW - cell differentiation KW - metallo-supramolecular polymer KW - interface KW - iron metabolism Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-197264 SN - 2073-4360 VL - 11 IS - 7 ER - TY - JOUR A1 - Philipp, Marius B. A1 - Levick, Shaun R. T1 - Exploring the potential of C-Band SAR in contributing to burn severity mapping in tropical savanna JF - Remote Sensing N2 - The ability to map burn severity and to understand how it varies as a function of time of year and return frequency is an important tool for landscape management and carbon accounting in tropical savannas. Different indices based on optical satellite imagery are typically used for mapping fire scars and for estimating burn severity. However, cloud cover is a major limitation for analyses using optical data over tropical landscapes. To address this pitfall, we explored the suitability of C-band Synthetic Aperture Radar (SAR) data for detecting vegetation response to fire, using experimental fires in northern Australia. Pre- and post-fire results from Sentinel-1 C-band backscatter intensity data were compared to those of optical satellite imagery and were corroborated against structural changes on the ground that we documented through terrestrial laser scanning (TLS). Sentinel-1 C-band backscatter (VH) proved sensitive to the structural changes imparted by fire and was correlated with the Normalised Burn Ratio (NBR) derived from Sentinel-2 optical data. Our results suggest that C-band SAR holds potential to inform the mapping of burn severity in savannas, but further research is required over larger spatial scales and across a broader spectrum of fire regime conditions before automated products can be developed. Combining both Sentinel-1 SAR and Sentinel-2 multi-spectral data will likely yield the best results for mapping burn severity under a range of weather conditions. KW - burn severity KW - Sentinel-1 KW - Sentinel-2 KW - terrestrial LiDAR Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-193789 SN - 2072-4292 VL - 12 IS - 1 ER - TY - JOUR A1 - Loda, Sophia A1 - Krebs, Jonathan A1 - Danhof, Sophia A1 - Schreder, Martin A1 - Solimando, Antonio G. A1 - Strifler, Susanne A1 - Rasche, Leo A1 - Kortüm, Martin A1 - Kerscher, Alexander A1 - Knop, Stefan A1 - Puppe, Frank A1 - Einsele, Hermann A1 - Bittrich, Max T1 - Exploration of artificial intelligence use with ARIES in multiple myeloma research JF - Journal of Clinical Medicine N2 - Background: Natural language processing (NLP) is a powerful tool supporting the generation of Real-World Evidence (RWE). There is no NLP system that enables the extensive querying of parameters specific to multiple myeloma (MM) out of unstructured medical reports. We therefore created a MM-specific ontology to accelerate the information extraction (IE) out of unstructured text. Methods: Our MM ontology consists of extensive MM-specific and hierarchically structured attributes and values. We implemented “A Rule-based Information Extraction System” (ARIES) that uses this ontology. We evaluated ARIES on 200 randomly selected medical reports of patients diagnosed with MM. Results: Our system achieved a high F1-Score of 0.92 on the evaluation dataset with a precision of 0.87 and recall of 0.98. Conclusions: Our rule-based IE system enables the comprehensive querying of medical reports. The IE accelerates the extraction of data and enables clinicians to faster generate RWE on hematological issues. RWE helps clinicians to make decisions in an evidence-based manner. Our tool easily accelerates the integration of research evidence into everyday clinical practice. KW - natural language processing KW - ontology KW - artificial intelligence KW - multiple myeloma KW - real world evidence Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-197231 SN - 2077-0383 VL - 8 IS - 7 ER - TY - JOUR A1 - Eder, Andreas B. A1 - Dignath, David T1 - Expected value of control and the motivational control of habitual action JF - Frontiers in Psychology N2 - A hallmark of habitual actions is that, once they are established, they become insensitive to changes in the values of action outcomes. In this article, we review empirical research that examined effects of posttraining changes in outcome values in outcome-selective Pavlovian-to-instrumental transfer (PIT) tasks. This review suggests that cue-instigated action tendencies in these tasks are not affected by weak and/or incomplete revaluation procedures (e.g., selective satiety) and substantially disrupted by a strong and complete devaluation of reinforcers. In a second part, we discuss two alternative models of a motivational control of habitual action: a default-interventionist framework and expected value of control theory. It is argued that the default-interventionist framework cannot solve the problem of an infinite regress (i.e., what controls the controller?). In contrast, expected value of control can explain control of habitual actions with local computations and feedback loops without (implicit) references to control homunculi. It is argued that insensitivity to changes in action outcomes is not an intrinsic design feature of habits but, rather, a function of the cognitive system that controls habitual action tendencies. KW - habit KW - outcome devaluation KW - Pavlovian-to-instrumental transfer KW - default-interventionist framework KW - expected value of control KW - cognitive control Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-195703 SN - 1664-1078 VL - 10 IS - 1812 ER - TY - JOUR A1 - Fathy, Moustafa A1 - Fawzy, Michael Atef A1 - Hintzsche, Henning A1 - Nikaido, Toshio A1 - Dandekar, Thomas A1 - Othman, Eman M. T1 - Eugenol exerts apoptotic effect and modulates the sensitivity of HeLa cells to cisplatin and radiation JF - Molecules N2 - Eugenol is a phytochemical present in different plant products, e.g., clove oil. Traditionally, it is used against a number of different disorders and it was suggested to have anticancer activity. In this study, the activity of eugenol was evaluated in a human cervical cancer (HeLa) cell line and cell proliferation was examined after treatment with various concentrations of eugenol and different treatment durations. Cytotoxicity was tested using lactate dehydrogenase (LDH) enzyme leakage. In order to assess eugenol’s potential to act synergistically with chemotherapy and radiotherapy, cell survival was calculated after eugenol treatment in combination with cisplatin and X-rays. To elucidate its mechanism of action, caspase-3 activity was analyzed and the expression of various genes and proteins was checked by RT-PCR and western blot analyses. Eugenol clearly decreased the proliferation rate and increased LDH release in a concentration- and time-dependent manner. It showed synergistic effects with cisplatin and X-rays. Eugenol increased caspase-3 activity and the expression of Bax, cytochrome c (Cyt-c), caspase-3, and caspase-9 and decreased the expression of B-cell lymphoma (Bcl)-2, cyclooxygenase-2 (Cox-2), and interleukin-1 beta (IL-1β) indicating that eugenol mainly induced cell death by apoptosis. In conclusion, eugenol showed antiproliferative and cytotoxic effects via apoptosis and also synergism with cisplatin and ionizing radiation in the human cervical cancer cell line. KW - eugenol KW - HeLa cells KW - cisplatin KW - radiation KW - apoptosis Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-193227 SN - 1420-3049 VL - 24 IS - 21 ER - TY - JOUR A1 - Mateos, Mariana A1 - Kang, Du A1 - Klopp, Christophe A1 - Parrinello, Hugues A1 - García-Olazábal, Mateo A1 - Schumer, Molly A1 - Jue, Nathaniel K. A1 - Guiguen, Yann A1 - Schartl, Manfred T1 - Draft genome assembly and annotation of the Gila Topminnow Poeciliopsis occidentalis JF - Frontiers in Ecology and Evolution N2 - No abstract available. KW - genome assembly KW - genome annotation KW - transposable elements KW - topminnow KW - mitochondrial genome Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-190339 SN - 2296-701X VL - 7 IS - 404 ER - TY - JOUR A1 - Kunz, Tobias C. A1 - Götz, Ralph A1 - Sauer, Markus A1 - Rudel, Thomas T1 - Detection of chlamydia developmental forms and secreted effectors by expansion microscopy JF - Frontiers in Cellular and Infection Microbiology N2 - Expansion microscopy (ExM) is a novel tool to improve the resolution of fluorescence-based microscopy that has not yet been used to visualize intracellular pathogens. Here we show the expansion of the intracellular pathogen Chlamydia trachomatis, enabling to differentiate its two distinct forms, catabolic active reticulate bodies (RB) and infectious elementary bodies (EB), on a conventional confocal microscope. We show that ExM enables the possibility to precisely locate chlamydial effector proteins, such as CPAF or Cdu1, within and outside of the chlamydial inclusion. Thus, we claim that ExM offers the possibility to address a broad range of questions and may be useful for further research on various intracellular pathogens. KW - expansion microscopy KW - chlamydia KW - secreted effectors KW - developmental forms KW - superresolution KW - imaging Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-195716 SN - 2235-2988 VL - 9 IS - 276 ER - TY - JOUR A1 - Feldheim, Jonas A1 - Kessler, Almuth F. A1 - Monoranu, Camelia M. A1 - Ernestus, Ralf-Ingo A1 - Löhr, Mario A1 - Hagemann, Carsten T1 - Changes of O\(^6\)-Methylguanine DNA Methyltransferase (MGMT) promoter methylation in glioblastoma relapse—a meta-analysis type literature review JF - Cancers N2 - Methylation of the O6-methylguanine DNA methyltransferase (MGMT) promoter has emerged as strong prognostic factor in the therapy of glioblastoma multiforme. It is associated with an improved response to chemotherapy with temozolomide and longer overall survival. MGMT promoter methylation has implications for the clinical course of patients. In recent years, there have been observations of patients changing their MGMT promoter methylation from primary tumor to relapse. Still, data on this topic are scarce. Studies often consist of only few patients and provide rather contrasting results, making it hard to draw a clear conclusion on clinical implications. Here, we summarize the previous publications on this topic, add new cases of changing MGMT status in relapse and finally combine all reports of more than ten patients in a statistical analysis based on the Wilson score interval. MGMT promoter methylation changes are seen in 115 of 476 analyzed patients (24%; CI: 0.21–0.28). We discuss potential reasons like technical issues, intratumoral heterogeneity and selective pressure of therapy. The clinical implications are still ambiguous and do not yet support a change in clinical practice. However, retesting MGMT methylation might be useful for future treatment decisions and we encourage clinical studies to address this topic KW - glioblastoma multiforme (GBM) KW - glioma KW - relapse KW - temozolomide KW - MGMT promoter methylation KW - therapy KW - resistance KW - recurrence Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-193040 SN - 2072-6694 VL - 11 IS - 12 ER - TY - JOUR A1 - Werner, Rudolf A. A1 - Kircher, Stefan A1 - Higuchi, Takahiro A1 - Kircher, Malte A1 - Schirbel, Andreas A1 - Wester, Hans-Jürgen A1 - Buck, Andreas K. A1 - Pomper, Martin G. A1 - Rowe, Steven P. A1 - Lapa, Constantin T1 - CXCR4-directed imaging in solid tumors JF - Frontiers in Oncology N2 - Despite histological evidence in various solid tumor entities, available experience with CXCR4-directed diagnostics and endoradiotherapy mainly focuses on hematologic diseases. With the goal of expanding the application of CXCR4 theranostics to solid tumors, we aimed to elucidate the feasibility of CXCR4-targeted imaging in a variety of such neoplasms. Methods: Nineteen patients with newly diagnosed, treatment-naïve solid tumors including pancreatic adenocarcinoma or neuroendocrine tumor, cholangiocarcinoma, hepatocellular carcinoma, renal cell carcinoma, ovarian cancer, and prostate cancer underwent [\(^{68}\)Ga]Pentixafor PET/CT. CXCR4-mediated uptake was assessed both visually and semi-quantitatively by evaluation of maximum standardized uptake values (SUV\(_{max}\)) of both primary tumors and metastases. With physiologic liver uptake as reference, tumor-to-background ratios (TBR) were calculated. [\(^{68}\)Ga]Pentixafor findings were further compared to immunohistochemistry and [\(^{18}\)F]FDG PET/CT. Results: On [\(^{68}\)Ga]Pentixafor PET/CT, 10/19 (52.6%) primary tumors were visually detectable with a median SUVmax of 5.4 (range, 1.7–16.0) and a median TBR of 2.6 (range, 0.8–7.4), respectively. The highest level of radiotracer uptake was identified in a patient with cholangiocarcinoma (SUVmax, 16.0; TBR, 7.4). The relatively low uptake on [\(^{68}\)Ga]Pentixafor was also noted in metastases, exhibiting a median SUVmax of 4.5 (range, 2.3–8.8; TBR, 1.7; range, 1.0–4.1). A good correlation between uptake on [\(^{68}\)Ga]Pentixafor and histological derived CXCR4 expression was noted (R = 0.62, P < 0.05). In the 3 patients in whom [\(^{18}\)F]FDG PET/CT was available, [\(^{68}\)Ga]Pentixafor exhibited lower uptake in all lesions. Conclusions: In this cohort of newly diagnosed, treatment-naïve patients with solid malignancies, CXCR4 expression as detected by [\(^{68}\)Ga]Pentixafor-PET/CT and immunohistochemistry was rather moderate. Thus, CXCR4-directed imaging may not play a major role in the management of solid tumors in the majority of patients. KW - CXCR4 KW - [68Ga]Pentixafor KW - theranostics KW - solid tumors KW - chemokine receptor Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-195678 SN - 2234-943X VL - 9 IS - 770 ER - TY - JOUR A1 - Hagemann, Carsten A1 - Neuhaus, Nikolas A1 - Dahlmann, Mathias A1 - Kessler, Almuth F. A1 - Kobelt, Dennis A1 - Herrmann, Pia A1 - Eyrich, Matthias A1 - Freitag, Benjamin A1 - Linsenmann, Thomas A1 - Monoranu, Camelia M. A1 - Ernestus, Ralf-Ingo A1 - Löhr, Mario A1 - Stein, Ulrike T1 - Circulating MACC1 transcripts in glioblastoma patients predict prognosis and treatment response JF - Cancers N2 - Glioblastoma multiforme is the most aggressive primary brain tumor of adults, but lacksreliable and liquid biomarkers. We evaluated circulating plasma transcripts of metastasis-associatedin colon cancer-1 (MACC1), a prognostic biomarker for solid cancer entities, for prediction of clinicaloutcome and therapy response in glioblastomas. MACC1 transcripts were significantly higher inpatients compared to controls. Low MACC1 levels clustered together with other prognosticallyfavorable markers. It was associated with patients’ prognosis in conjunction with the isocitratedehydrogenase (IDH) mutation status: IDH1 R132H mutation and low MACC1 was most favorable(median overall survival (OS) not yet reached), IDH1 wildtype and high MACC1 was worst (medianOS 8.1 months), while IDH1 wildtype and low MACC1 was intermediate (median OS 9.1 months).No patients displayed IDH1 R132H mutation and high MACC1. Patients with low MACC1 levelsreceiving standard therapy survived longer (median OS 22.6 months) than patients with high MACC1levels (median OS 8.1 months). Patients not receiving the standard regimen showed the worstprognosis, independent of MACC1 levels (low: 6.8 months, high: 4.4 months). Addition of circulatingMACC1 transcript levels to the existing prognostic workup may improve the accuracy of outcomeprediction and help define more precise risk categories of glioblastoma patients. KW - metastasis-associated in colon cancer 1 (MACC1) KW - glioblastoma multiforme KW - liquid biopsy KW - therapy response KW - prognostic marker Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-197327 SN - 2072-6694 VL - 11 IS - 6 ER - TY - JOUR A1 - John, Vini A1 - Kotze, Leigh A. A1 - Ribechini, Eliana A1 - Walzl, Gerhard A1 - Du Plessis, Nelita A1 - Lutz, Manfred B. T1 - Caveolin-1 controls vesicular TLR2 expression, p38 signaling and T cell suppression in BCG infected murine monocytic myeloid-derived suppressor cells JF - Frontiers in Immunology N2 - Monocytic myeloid-derived suppressor cells (M-MDSCs) and granulocytic MDSCs (G-MDSCs) have been found to be massively induced in TB patients as well in murine Mtb infection models. However, the interaction of mycobacteria with MDSCs and its role in TB infection is not well studied. Here, we investigated the role of Cav-1 for MDSCs infected with Mycobacterium bovis Bacille-Calmette-Guerín (BCG). MDSCs that were generated from murine bone marrow (MDSCs) of wild-type (WT) or Cav1\(^{−/−}\) mice upregulated Cav-1, TLR4 and TLR2 expression after BCG infection on the cell surface. However, Cav-1 deficiency resulted in a selective defect of intracellular TLR2 levels predominantly in the M-MDSC subset. Further analysis indicated no difference in the phagocytosis of BCG by M-MDSCs from WT and Cav1\(^{−/−}\) mice or caveosome formation, but a reduced capacity to up-regulate surface markers, to secrete various cytokines, to induce iNOS and NO production required for suppression of T cell proliferation, whereas Arg-1 was not affected. Among the signaling pathways affected by Cav-1 deficiency, we found lower phosphorylation of the p38 mitogen-activated protein kinase (MAPK). Together, our findings implicate that (i) Cav-1 is dispensable for the internalization of BCG, (ii) vesicular TLR2 signaling in M-MDSCs is a major signaling pathway induced by BCG, (iii) vesicular TLR2 signals are controlled by Cav-1, (iv) vesicular TLR2/Cav-1 signaling is required for T cell suppressor functions. KW - myeloid-derived suppressor cell (MDSC) KW - caveolin-1 (Cav-1) KW - TLR2 KW - TLR4 KW - BCG KW - T cell suppression Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-195528 SN - 1664-3224 VL - 10 IS - 2826 ER - TY - JOUR A1 - Heydarian, Motaharehsadat A1 - Yang, Tao A1 - Schweinlin, Matthias A1 - Steinke, Maria A1 - Walles, Heike A1 - Rudel, Thomas A1 - Kozjak-Pavlovic, Vera T1 - Biomimetic human tissue model for long-term study of Neisseria gonorrhoeae infection JF - Frontiers in Microbiology N2 - Gonorrhea is the second most common sexually transmitted infection in the world and is caused by Gram-negative diplococcus Neisseria gonorrhoeae. Since N. gonorrhoeae is a human-specific pathogen, animal infection models are only of limited use. Therefore, a suitable in vitro cell culture model for studying the complete infection including adhesion, transmigration and transport to deeper tissue layers is required. In the present study, we generated three independent 3D tissue models based on porcine small intestinal submucosa (SIS) scaffold by co-culturing human dermal fibroblasts with human colorectal carcinoma, endometrial epithelial, and male uroepithelial cells. Functional analyses such as transepithelial electrical resistance (TEER) and FITC-dextran assay indicated the high barrier integrity of the created monolayer. The histological, immunohistochemical, and ultra-structural analyses showed that the 3D SIS scaffold-based models closely mimic the main characteristics of the site of gonococcal infection in human host including the epithelial monolayer, the underlying connective tissue, mucus production, tight junction, and microvilli formation. We infected the established 3D tissue models with different N. gonorrhoeae strains and derivatives presenting various phenotypes regarding adhesion and invasion. The results indicated that the disruption of tight junctions and increase in interleukin production in response to the infection is strain and cell type-dependent. In addition, the models supported bacterial survival and proved to be better suitable for studying infection over the course of several days in comparison to commonly used Transwell® models. This was primarily due to increased resilience of the SIS scaffold models to infection in terms of changes in permeability, cell destruction and bacterial transmigration. In summary, the SIS scaffold-based 3D tissue models of human mucosal tissues represent promising tools for investigating N. gonorrhoeae infections under close-to-natural conditions. KW - 3D tissue model KW - small intestinal submucosa scaffold KW - co-culture KW - infection KW - Neisseria gonorrhoeae Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-197912 SN - 1664-302X VL - 10 IS - 1740 ER - TY - JOUR A1 - Rösler, Lara A1 - Rubo, Marius A1 - Gamer, Matthias T1 - Artificial faces predict gaze allocation in complex dynamic scenes JF - Frontiers in Psychology N2 - Both low-level physical saliency and social information, as presented by human heads or bodies, are known to drive gaze behavior in free-viewing tasks. Researchers have previously made use of a great variety of face stimuli, ranging from photographs of real humans to schematic faces, frequently without systematically differentiating between the two. In the current study, we used a Generalized Linear Mixed Model (GLMM) approach to investigate to what extent schematic artificial faces can predict gaze when they are presented alone or in competition with real human faces. Relative differences in predictive power became apparent, while GLMMs suggest substantial effects for real and artificial faces in all conditions. Artificial faces were accordingly less predictive than real human faces but still contributed significantly to gaze allocation. These results help to further our understanding of how social information guides gaze in complex naturalistic scenes. KW - social attention KW - faces KW - physical saliency KW - visual perception KW - naturalistic scenes KW - eye movements Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-193024 SN - 1664-1078 VL - 10 IS - 2877 ER - TY - JOUR A1 - Hoche, Joscha A1 - Schulz, Alexander A1 - Dietrich, Lysanne Monika A1 - Humeniuk, Alexander A1 - Stolte, Matthias A1 - Schmidt, David A1 - Brixner, Tobias A1 - Würthner, Frank A1 - Mitric, Roland T1 - The origin of the solvent dependence of fluorescence quantum yields in dipolar merocyanine dyes JF - Chemical Science N2 - Fluorophores with high quantum yields are desired for a variety of applications. Optimization of promising chromophores requires an understanding of the non-radiative decay channels that compete with the emission of photons. We synthesized a new derivative of the famous laser dye 4-dicyanomethylen-2-methyl-6-p-dimethylaminostyryl-4H-pyran (DCM),i.e., merocyanine 4-(dicyanomethylene)-2-tert-butyl-6-[3-(3-butyl-benzothiazol-2-ylidene)1-propenyl]-4H-pyran (DCBT). We measured fluorescence lifetimes and quantum yields in a variety of solvents and found a trend opposite to the energy gap law.This motivated a theoretical investigation into the possible non-radiative decay channels. We propose that a barrier to a conical intersection exists that is very sensitive to the solvent polarity. The conical intersection is characterized by a twisted geometry which allows a subsequent photoisomerization. Transient absorption measurements confirmed the formation of a photoisomer in unpolar solvents, while the measurements of fluorescence quantum yields at low temperature demonstrated the existence of an activation energy barrier. KW - solvent-dependent fluorescence yield Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-198707 UR - https://doi.org/10.1039/C9SC05012D VL - 10 ER - TY - JOUR A1 - Schlenkrich, Oliver T1 - Identifying Profiles of Democracies: A Cluster Analysis Based on the Democracy Matrix Dataset from 1900 to 2017 JF - Politics and Governance N2 - This study examines types of democracies that result from trade-offs within the democratic quality. Recently, the existence and relevance of trade-offs has been widely discussed. The idea is that the functions associated with the quality of democracy cannot all be maximized simultaneously. Thus, trade-offs are expressed in distinct profiles of democracy. Different profiles of democracy favour certain democracy dimensions over others due to their institutional design. Conceptually, we differentiate between four different democracy profiles: a libertarian-majoritarian (high political freedom, lower political equality, and lower political and legal control values), an egalitarian-majoritarian (high equality combined with lower freedom and control values), as well as two control-focused democracy profiles (high control values either with high degrees of freedom or high degrees of equality). We apply a cluster analysis with a focus on cluster validation on the Democracy Matrix dataset—a customized version of the Varieties-of-Democracy dataset. To increase the robustness of the cluster results, this study uses several different cluster algorithms, multiple fit indices as well as data resampling techniques. Based on all democracies between 1900 and 2017, we find strong empirical evidence for these democracy profiles. Finally, we discuss the temporal development and spatial distribution of the democracy profiles globally across the three waves of democracy, as well as for individual countries. KW - cluster analysis KW - democracy KW - democracy profiles KW - quality of democracy KW - trade-offs Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-150882 SN - 2183-2463 VL - 7 IS - 4 ER - TY - JOUR A1 - Landman, Todd A1 - Lauth, Hans-Joachim T1 - Political Trade-Offs: Democracy and Governance in a Changing World JF - Politics and Governance N2 - The investigation of trade-offs in political science receives only limited attention, although many scholars acknowledge the importance of trade-offs across a variety of different areas. A systematic and comprehensive examination of the topic is missing. This thematic issue of Politics and Governance sheds light on this research deficit by providing a holistic but also an integrative view on trade-offs in the political realm for the first time. Researchers of trade-offs from different political areas present and discuss their findings, and promote a fruitful exchange, which overcomes the current isolation of the approaches. They consider the theoretical and methodological questions as well as the identification of empirical tradeoffs. Furthermore, they provide insights into the possibility to balance trade-offs and strategies, which could help actors to find such compromises. KW - balancing trade-offs KW - constructed trade-offs KW - logical trade-offs KW - trade-offs Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-144308 SN - 2183-2463 VL - 7 IS - 4 ER - TY - JOUR A1 - Steinmetzger, Christian A1 - Bessi, Irene A1 - Lenz, Ann-Kathrin A1 - Höbartner, Claudia T1 - Structure-fluorescence activation relationships of a large Stokes shift fluorogenic RNA aptamer JF - Nucleic Acids Research N2 - The Chili RNA aptamer is a 52 nt long fluorogen-activating RNA aptamer (FLAP) that confers fluorescence to structurally diverse derivatives of fluorescent protein chromophores. A key feature of Chili is the formation of highly stable complexes with different ligands, which exhibit bright, highly Stokes-shifted fluorescence emission. In this work, we have analyzed the interactions between the Chili RNA and a family of conditionally fluorescent ligands using a variety of spectroscopic, calorimetric and biochemical techniques to reveal key structure - fluorescence activation relationships (SFARs). The ligands under investigation form two categories with emission maxima of ~540 nm or ~590 nm, respectively, and bind with affinities in the nanomolar to low-micromolar range. Isothermal titration calorimetry was used to elucidate the enthalpic and entropic contributions to binding affinity for a cationic ligand that is unique to the Chili aptamer. In addition to fluorescence activation, ligand binding was also observed by NMR spectroscopy, revealing characteristic signals for the formation of a G-quadruplex only upon ligand binding. These data shed light on the molecular features required and responsible for the large Stokes shift and the strong fluorescence enhancement of red and green emitting RNA-chromophore complexes. KW - Chili RNA Aptamer KW - fluorogen-activating RNA aptamer (FLAP) KW - Stokes-shifted fluorescence emission KW - key structure - fluorescence activation relationships (SFARs) KW - ligand binding Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-192340 ER - TY - JOUR A1 - Yang, Manli A1 - Rajeeve, Karthika A1 - Rudel, Thomas A1 - Dandekar, Thomas T1 - Comprehensive Flux Modeling of Chlamydia trachomatis Proteome and qRT-PCR Data Indicate Biphasic Metabolic Differences Between Elementary Bodies and Reticulate Bodies During Infection JF - Frontiers in Microbiology N2 - Metabolic adaptation to the host cell is important for obligate intracellular pathogens such as Chlamydia trachomatis (Ct). Here we infer the flux differences for Ct from proteome and qRT-PCR data by comprehensive pathway modeling. We compare the comparatively inert infectious elementary body (EB) and the active replicative reticulate body (RB) systematically using a genome-scale metabolic model with 321 metabolites and 277 reactions. This did yield 84 extreme pathways based on a published proteomics dataset at three different time points of infection. Validation of predictions was done by quantitative RT-PCR of enzyme mRNA expression at three time points. Ct’s major active pathways are glycolysis, gluconeogenesis, glycerol-phospholipid (GPL) biosynthesis (support from host acetyl-CoA) and pentose phosphate pathway (PPP), while its incomplete TCA and fatty acid biosynthesis are less active. The modeled metabolic pathways are much more active in RB than in EB. Our in silico model suggests that EB and RB utilize folate to generate NAD(P)H using independent pathways. The only low metabolic flux inferred for EB involves mainly carbohydrate metabolism. RB utilizes energy -rich compounds to generate ATP in nucleic acid metabolism. Validation data for the modeling include proteomics experiments (model basis) as well as qRT-PCR confirmation of selected metabolic enzyme mRNA expression differences. The metabolic modeling is made fully available here. Its detailed insights and models on Ct metabolic adaptations during infection are a useful modeling basis for future studies. KW - metabolic modeling KW - metabolic flux KW - infection biology KW - elementary body KW - reticulate body KW - Chlamydia trachomatis Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-189434 SN - 1664-302X VL - 10 IS - 2350 ER - TY - JOUR A1 - Hupp, Sabrina A1 - Rosenkranz, Maaria A1 - Bonfig, Katharina A1 - Pandey, Chandana A1 - Roitsch, Thomas T1 - Noninvasive Phenotyping of Plant–Pathogen Interaction: Consecutive In Situ Imaging of Fluorescing Pseudomonas syringae, Plant Phenolic Fluorescence, and Chlorophyll Fluorescence in Arabidopsis Leaves JF - Frontiers in Plant Science N2 - Plant–pathogen interactions have been widely studied, but mostly from the site of the plant secondary defense. Less is known about the effects of pathogen infection on plant primary metabolism. The possibility to transform a fluorescing protein into prokaryotes is a promising phenotyping tool to follow a bacterial infection in plants in a noninvasive manner. In the present study, virulent and avirulent Pseudomonas syringae strains were transformed with green fluorescent protein (GFP) to follow the spread of bacteria in vivo by imaging Pulse-Amplitude-Modulation (PAM) fluorescence and conventional binocular microscopy. The combination of various wavelengths and filters allowed simultaneous detection of GFP-transformed bacteria, PAM chlorophyll fluorescence, and phenolic fluorescence from pathogen-infected plant leaves. The results show that fluorescence imaging allows spatiotemporal monitoring of pathogen spread as well as phenolic and chlorophyll fluorescence in situ, thus providing a novel means to study complex plant–pathogen interactions and relate the responses of primary and secondary metabolism to pathogen spread and multiplication. The study establishes a deeper understanding of imaging data and their implementation into disease screening. KW - green fluorescence protein (GFP) KW - plant–pathogen interaction KW - imaging PAM KW - chlorophyll fluorescence imaging KW - phenolic compounds Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-189425 SN - 1664-462X VL - 10 IS - 1239 ER - TY - JOUR A1 - Kasaragod, Vikram Babu A1 - Schindelin, Hermann T1 - Structure of Heteropentameric GABAA Receptors and Receptor-Anchoring Properties of Gephyrin JF - Frontiers in Molecular Neuroscience N2 - γ-Aminobutyric acid type A receptors (GABAARs) mediate the majority of fast synaptic inhibition in the central nervous system (CNS). GABAARs belong to the Cys-loop superfamily of pentameric ligand-gated ion channels (pLGIC) and are assembled from 19 different subunits. As dysfunctional GABAergic neurotransmission manifests itself in neurodevelopmental disorders including epilepsy and anxiety, GABAARs are key drug targets. The majority of synaptic GABAARs are anchored at the inhibitory postsynaptic membrane by the principal scaffolding protein gephyrin, which acts as the central organizer in maintaining the architecture of the inhibitory postsynaptic density (iPSD). This interaction is mediated by the long intracellular loop located in between transmembrane helices 3 and 4 (M3–M4 loop) of the receptors and a universal receptor-binding pocket residing in the C-terminal domain of gephyrin. In 2014, the crystal structure of the β3-homopentameric GABAAR provided crucial information regarding the architecture of the receptor; however, an understanding of the structure and assembly of heteropentameric receptors at the atomic level was lacking. This review article will highlight recent advances in understanding the structure of heteropentameric synaptic GABAARs and how these structures have provided fundamental insights into the assembly of these multi-subunit receptors as well as their modulation by diverse ligands including the physiological agonist GABA. We will further discuss the role of gephyrin in the anchoring of synaptic GABAARs and glycine receptors (GlyRs), which are crucial for maintaining the architecture of the iPSD. Finally, we will also summarize how anti-malarial artemisinin drugs modulate gephyrin-mediated inhibitory neurotransmission. KW - GABAA KW - gephyrin KW - diazepam KW - GABA KW - PIP2 KW - artemisinin KW - Cryo-EM KW - inhibitory neurotransmission Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-189308 SN - 1662-5099 VL - 12 ER - TY - JOUR A1 - Zhang, Yonghong A1 - Zheng, Lanlan A1 - Zheng, Yan A1 - Zhou, Chao A1 - Huang, Ping A1 - Xiao, Xiao A1 - Zhao, Yongheng A1 - Hao, Xincai A1 - Hu, Zhubing A1 - Chen, Qinhua A1 - Li, Hongliang A1 - Wang, Xuanbin A1 - Fukushima, Kenji A1 - Wang, Guodong A1 - Li, Chen T1 - Assembly and Annotation of a Draft Genome of the Medicinal Plant Polygonum cuspidatum JF - Frontiers in Plant Science N2 - Polygonum cuspidatum (Japanese knotweed, also known as Huzhang in Chinese), a plant that produces bioactive components such as stilbenes and quinones, has long been recognized as important in traditional Chinese herbal medicine. To better understand the biological features of this plant and to gain genetic insight into the biosynthesis of its natural products, we assembled a draft genome of P. cuspidatum using Illumina sequencing technology. The draft genome is ca. 2.56 Gb long, with 71.54% of the genome annotated as transposable elements. Integrated gene prediction suggested that the P. cuspidatum genome encodes 55,075 functional genes, including 6,776 gene families that are conserved in the five eudicot species examined and 2,386 that are unique to P. cuspidatum. Among the functional genes identified, 4,753 are predicted to encode transcription factors. We traced the gene duplication history of P. cuspidatum and determined that it has undergone two whole-genome duplication events about 65 and 6.6 million years ago. Roots are considered the primary medicinal tissue, and transcriptome analysis identified 2,173 genes that were expressed at higher levels in roots compared to aboveground tissues. Detailed phylogenetic analysis demonstrated expansion of the gene family encoding stilbene synthase and chalcone synthase enzymes in the phenylpropanoid metabolic pathway, which is associated with the biosynthesis of resveratrol, a pharmacologically important stilbene. Analysis of the draft genome identified 7 abscisic acid and water deficit stress-induced protein-coding genes and 14 cysteine-rich transmembrane module genes predicted to be involved in stress responses. The draft de novo genome assembly produced in this study represents a valuable resource for the molecular characterization of medicinal compounds in P. cuspidatum, the improvement of this important medicinal plant, and the exploration of its abiotic stress resistance. KW - genome assembly KW - resveratrol biosynthesis KW - whole-genome duplication KW - medicinal plant KW - stress tolerance KW - Polygonum cuspidatum Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-189279 SN - 1664-462X VL - 10 ER - TY - JOUR A1 - Brückner, Tobias A1 - Dewhurst, Rian D. A1 - Dellermann, Theresa A1 - Müller, Marcel A1 - Braunschweig, Holger T1 - Mild synthesis of diboryldiborenes by diboration of B–B triple bonds JF - Chemical Science N2 - A set of diboryldiborenes are prepared by the mild, catalyst-free, room-temperature diboration of the B–B triple bonds of doubly base-stabilized diborynes. Two of the product diboryldiborenes are found to be air- and water-stable in the solid state, an effect that is attributed to their high crystallinity and extreme insolubility in a wide range of solvents. KW - boron KW - diborenes KW - diboration KW - triple bonds KW - diborynes Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-186306 VL - 10 ER - TY - JOUR A1 - Ramler, Jacqueline A1 - Poater, Jordi A1 - Hirsch, Florian A1 - Ritschel, Benedikt A1 - Fischer, Ingo A1 - Bickelhaupt, F. Matthias A1 - Lichtenberg, Crispin T1 - Carbon monoxide insertion at a heavy p-block element: unprecedented formation of a cationic bismuth carbamoyl JF - Chemical Science N2 - Major advances in the chemistry of 5th and 6th row heavy p-block element compounds have recently uncovered intriguing reactivity patterns towards small molecules such as H\(_2\), CO\(_2\), and ethylene. However, well-defined, homogeneous insertion reactions with carbon monoxide, one of the benchmark substrates in this field, have not been reported to date. We demonstrate here, that a cationic bismuth amide undergoes facile insertion of CO into the Bi–N bond under mild conditions. This approach grants direct access to the first cationic bismuth carbamoyl species. Its characterization by NMR, IR, and UV/vis spectroscopy, elemental analysis, single-crystal X-ray analysis, cyclic voltammetry, and DFT calculations revealed intriguing properties, such as a reversible electron transfer at the bismuth center and an absorption feature at 353 nm ascribed to a transition involving σ- and π-type orbitals of the bismuth-carbamoyl functionality. A combined experimental and theoretical approach provided insight into the mechanism of CO insertion. The substrate scope could be extended to isonitriles. KW - carbon monoxide KW - p-block element Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-181627 VL - 10 ER - TY - JOUR A1 - Werner, Rudolf A. A1 - Ordonez, Alvaro A. A1 - Sanchez-Bautista, Julian A1 - Marcus, Charles A1 - Lapa, Constantin A1 - Rowe, Steven P. A1 - Pomper, Martin G. A1 - Leal, Jeffrey P. A1 - Lodge, Martin A. A1 - Javadi, Mehrbod S. A1 - Jain, Sanjay K. A1 - Higuchi, Takahiro T1 - Novel functional renal PET imaging with 18F-FDS in human subjects JF - Clinical Nuclear Medicine N2 - The novel PET probe 2-deoxy-2-18F-fluoro-D-sorbitol (18F-FDS) has demonstrated favorable renal kinetics in animals. We aimed to elucidate its imaging properties in two human volunteers. 18F-FDS was produced by a simple one-step reduction from 18F-FDG. On dynamic renal PET, the cortex was delineated and activity gradually transited in the parenchyma, followed by radiotracer excretion. No adverse effects were reported. Given the higher spatiotemporal resolution of PET relative to conventional scintigraphy, 18F-FDS PET offers a more thorough evaluation of human renal kinetics. Due to its simple production from 18F-FDG, 18F-FDS is virtually available at any PET facility with radiochemistry infrastructure. KW - 2-deoxy-2-18F-fluoro-D-sorbitol KW - Positronen-Emissions-Tomografie KW - 18F-FDS KW - renal imaging KW - Positron-Emission Tomography KW - split renal function KW - kidney Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-174634 SN - 0363-9762 VL - 44 IS - 5 ER - TY - JOUR A1 - Wagner, Johanna A1 - Eiken, Barbara A1 - Haubitz, Imme A1 - Lichthardt, Sven A1 - Matthes, Niels A1 - Löb, Stefan A1 - Klein, Ingo A1 - Germer, Christoph-Thomas A1 - Wiegering, Armin T1 - Suprapubic bladder drainage and epidural catheters following abdominal surgery—a risk for urinary tract infections? JF - PLoS ONE N2 - Background Epidural catheters are state of the art for postoperative analgesic in abdominal surgery. Due to neurolysis it can lead to postoperative urinary tract retention (POUR), which leads to prolonged bladder catheterization, which has an increased risk for urinary tract infections (UTI). Our aim was to identify the current perioperative management of urinary catheters and, second, to identify the optimal time of suprapubic bladder catheter removal in regard to the removal of the epidural catheter. Methods We sent a questionnaire to 102 German hospitals and analyzed the 83 received answers to evaluate the current handling of bladder drainage and epidural catheters. Then, we conducted a retrospective study including 501 patients, who received an epidural and suprapubic catheter after abdominal surgery at the University Hospital Würzburg. We divided the patients into three groups according to the point in time of suprapubic bladder drainage removal in regard to the removal of the epidural catheter and analyzed the onset of a UTI. Results Our survey showed that in almost all hospitals (98.8%), patients received an epidural catheter and a bladder drainage after abdominal surgery. The point in time of urinary catheter removal was equally distributed between before, simultaneously and after the removal of the epidural catheter (respectively: ~28–29%). The retrospective study showed a catheter-associated UTI in 6.7%. Women were affected significantly more often than men (10,7% versus 2,5%, p<0.001). There was a non-significant trend to more UTIs when the suprapubic catheter was removed after the epidural catheter (before: 5.7%, after: 8.4%). Conclusion The point in time of suprapubic bladder drainage removal in relation to the removal of the epidural catheter does not seem to correlate with the rate of UTIs. The current handling in Germany is inhomogeneous, so further studies to standardize treatment are recommended. KW - catheters KW - epidural block KW - bladder KW - urinary tract infections KW - abdominal surgery KW - catheterization KW - surgical and invasive medical procedures KW - rectum Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-177731 VL - 14 IS - 1 ER - TY - JOUR A1 - Westermann, Alexander J. A1 - Venturini, Elisa A1 - Sellin, Mikael E. A1 - Förstner, Konrad U. A1 - Hardt, Wolf-Dietrich A1 - Vogel, Jörg T1 - The major RNA-binding protein ProQ impacts virulence gene expression in Salmonella enterica serovar Typhimurium JF - mBio N2 - FinO domain proteins such as ProQ of the model pathogen Salmonella enterica have emerged as a new class of major RNA-binding proteins in bacteria. ProQ has been shown to target hundreds of transcripts, including mRNAs from many virulence regions, but its role, if any, in bacterial pathogenesis has not been studied. Here, using a Dual RNA-seq approach to profile ProQ-dependent gene expression changes as Salmonella infects human cells, we reveal dysregulation of bacterial motility, chemotaxis, and virulence genes which is accompanied by altered MAPK (mitogen-activated protein kinase) signaling in the host. Comparison with the other major RNA chaperone in Salmonella, Hfq, reinforces the notion that these two global RNA-binding proteins work in parallel to ensure full virulence. Of newly discovered infection-associated ProQ-bound small noncoding RNAs (sRNAs), we show that the 3′UTR-derived sRNA STnc540 is capable of repressing an infection-induced magnesium transporter mRNA in a ProQ-dependent manner. Together, this comprehensive study uncovers the relevance of ProQ for Salmonella pathogenesis and highlights the importance of RNA-binding proteins in regulating bacterial virulence programs. IMPORTANCE The protein ProQ has recently been discovered as the centerpiece of a previously overlooked “third domain” of small RNA-mediated control of gene expression in bacteria. As in vitro work continues to reveal molecular mechanisms, it is also important to understand how ProQ affects the life cycle of bacterial pathogens as these pathogens infect eukaryotic cells. Here, we have determined how ProQ shapes Salmonella virulence and how the activities of this RNA-binding protein compare with those of Hfq, another central protein in RNA-based gene regulation in this and other bacteria. To this end, we apply global transcriptomics of pathogen and host cells during infection. In doing so, we reveal ProQ-dependent transcript changes in key virulence and host immune pathways. Moreover, we differentiate the roles of ProQ from those of Hfq during infection, for both coding and noncoding transcripts, and provide an important resource for those interested in ProQ-dependent small RNAs in enteric bacteria. KW - Hfq KW - noncoding RNA KW - ProQ KW - RNA-seq KW - bacterial pathogen KW - posttranscriptional control Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-177722 VL - 10 IS - 1 ER - TY - JOUR A1 - Suchotzki, Kristina A1 - Kakavand, Aileen A1 - Gamer, Matthias T1 - Validity of the reaction time concealed information test in a prison sample JF - Frontiers in Psychiatry N2 - Detecting whether a suspect possesses incriminating (e.g., crime-related) information can provide valuable decision aids in court. To this means, the Concealed Information Test (CIT) has been developed and is currently applied on a regular basis in Japan. But whereas research has revealed a high validity of the CIT in student and normal populations, research investigating its validity in forensic samples in scarce. This applies even more to the reaction time-based CIT (RT-CIT), where no such research is available so far. The current study tested the application of the RT-CIT for an imaginary mock crime scenario both in a sample of prisoners (n = 27) and a matched control group (n = 25). Results revealed a high validity of the RT-CIT for discriminating between crime-related and crime-unrelated information, visible in medium to very high effect sizes for error rates and reaction times. Interestingly, in accordance with theories that criminal offenders may have worse response inhibition capacities and that response inhibition plays a crucial role in the RT-CIT, CIT-effects in the error rates were even elevated in the prisoners compared to the control group. No support for this hypothesis could, however, be found in reaction time CIT-effects. Also, performance in a standard Stroop task, that was conducted to measure executive functioning, did not differ between both groups and no correlation was found between Stroop task performance and performance in the RT-CIT. Despite frequently raised concerns that the RT-CIT may not be applicable in non-student and forensic populations, our results thereby do suggest that such a use may be possible and that effects seem to be quite large. Future research should build up on these findings by increasing the realism of the crime and interrogation situation and by further investigating the replicability and the theoretical substantiation of increased effects in non-student and forensic samples. KW - concealed information test KW - deception KW - lying KW - reaction times KW - inmates KW - forensic sample Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-177714 VL - 9 IS - 745 ER - TY - JOUR A1 - Goos, Carina A1 - Dejung, Mario A1 - Wehman, Ann M. A1 - M-Natus, Elisabeth A1 - Schmidt, Johannes A1 - Sunter, Jack A1 - Engstler, Markus A1 - Butter, Falk A1 - Kramer, Susanne T1 - Trypanosomes can initiate nuclear export co-transcriptionally JF - Nucleic Acids Research N2 - The nuclear envelope serves as important messenger RNA (mRNA) surveillance system. In yeast and human, several control systems act in parallel to prevent nuclear export of unprocessed mRNAs. Trypanosomes lack homologues to most of the involved proteins and their nuclear mRNA metabolism is non-conventional exemplified by polycistronic transcription and mRNA processing by trans-splicing. We here visualized nuclear export in trypanosomes by intra- and intermolecular multi-colour single molecule FISH. We found that, in striking contrast to other eukaryotes, the initiation of nuclear export requires neither the completion of transcription nor splicing. Nevertheless, we show that unspliced mRNAs are mostly prevented from reaching the nucleus-distant cytoplasm and instead accumulate at the nuclear periphery in cytoplasmic nuclear periphery granules (NPGs). Further characterization of NPGs by electron microscopy and proteomics revealed that the granules are located at the cytoplasmic site of the nuclear pores and contain most cytoplasmic RNA-binding proteins but none of the major translation initiation factors, consistent with a function in preventing faulty mRNAs from reaching translation. Our data indicate that trypanosomes regulate the completion of nuclear export, rather than the initiation. Nuclear export control remains poorly understood, in any organism, and the described way of control may not be restricted to trypanosomes. KW - molecular biology KW - nuclear export KW - trypanosomes KW - mRNA KW - nuclear envelope Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-177709 VL - 47 IS - 1 ER - TY - JOUR A1 - Petschke, Danny A1 - Helm, Ricardo A1 - Staab, Torsten E.M. T1 - Data on pure tin by Positron Annihilation Lifetime Spectroscopy (PALS) acquired with a semi-analog/digital setup using DDRS4PALS JF - Data in Brief N2 - Positron annihilation lifetime spectroscopy (PALS) provides a powerful technique for non-destructive microstructure investigations in a broad field of material classes such as metals, semiconductors, polymers or porous glasses. Even though this method is well established for more than five decades, no proper standardization for the used setup configuration and subsequent data processing exists. Eventually, this could lead to an insufficiency of data reproducibility and avoidable deviations. Here we present experimentally obtained and simulated data of positron lifetime spectra at various statistics measured on pure tin (4N-Sn) by using a semi-analog/digital setup, where the digital section consists of the DRS4 evaluation board, “Design and performance of the 6 GHz waveform digitizing chip DRS4” [1]. The analog section consists of nuclear instrument modules (NIM), which externally trigger the DRS4 evaluation board to reduce the digitization and, thus, increase the acquisition efficiency. For the experimentally obtained lifetime spectra, 22Na sealed in Kapton foil served as a positron source, whereas 60Co was used for the acquisition of the prompt spectrum, i.e. the quasi instrument response function. Both types of measurements were carried out under the same conditions. All necessary data and information regarding the data acquisition and data reduction are provided to allow reproducibility by other research groups. KW - positron KW - positron annihilation lifetime spectroscopy KW - PALS Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-177698 VL - 22 ER - TY - JOUR A1 - Linsenmann, Thomas A1 - Monoranu, Camelia M. A1 - Alkonyi, Balint A1 - Westermaier, Thomas A1 - Hagemann, Carsten A1 - Kessler, Almuth F. A1 - Ernestus, Ralf-Ingo A1 - Löhr, Mario T1 - Cerebellar liponeurocytoma - molecular signature of a rare entity and the importance of an accurate diagnosis JF - Interdisciplinary Neurosurgery N2 - Background: Cerebellar liponeurocytoma is an extremely rare tumour entity of the central nervous system. It is histologically characterised by prominent neuronal/neurocytic differentiation with focal lipidisation and corresponding histologically to WHO grade II. It typically develops in adults, and usually shows a low proliferative potential. Recurrences have been reported in almost 50% of cases, and in some cases the recurrent tumour may display increased mitotic activity and proliferation index, vascular proliferations and necrosis. Thus pathological diagnosis of liponeurocytoma is challenging. This case presentation highlights the main clinical, radiographic and pathological features of a cerebellar liponeurocytoma. Case presentation: A 59-year-old, right-handed woman presented at our department with a short history of persistent headache, vertigo and gait disturbances. Examination at presentation revealed that the patient was awake, alert and fully oriented. The cranial nerve status was normal. Uncertainties were noted in the bilateral finger-to-nose testing with bradydiadochokinesis on both sides. Strength was full and no pronator drift was observed. Sensation was intact. No signs of pyramidal tract dysfunction were detected. Her gait appeared insecure. The patient underwent surgical resection. Afterward no further disturbances could be detected. Conclusions: To date >40 cases of liponeurocytoma have been reported, including cases with supratentorial location. A review of the 5 published cases of recurrent cerebellar. Liponeurocytoma revealed that the median interval between the first and second relapse was rather short, indicating uncertain malignant potential. The most recent WHO classification of brain tumours (2016) classifies the cerebellar liponeurocytoma as a separate entity and assigns the tumour to WHO grade II. Medulloblastoma is the most important differential diagnosis commonly seen in children and young adults. In contrast, cerebellar liponeurocytoma is typically diagnosed in adults. The importance of accurate diagnosis should not be underestimated especially in the view of possible further therapeutic interventions and for the determination of the patient's prognosis. KW - liponeurocytoma KW - neurocytoma KW - medulloblastoma KW - molecular signature Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-177652 VL - 16 ER - TY - JOUR A1 - Bratengeier, Klaus A1 - Holubyev, Kostyantyn A1 - Wegener, Sonja T1 - Steeper dose gradients resulting from reduced source to target distance—a planning system independent study JF - Journal of Applied Clinical Medical Physics N2 - Purpose: To quantify the contribution of penumbra in the improvement of healthy tissue sparing at reduced source‐to‐axis distance (SAD) for simple spherical target and different prescription isodoses (PI). Method: A TPS‐independent method was used to estimate three‐dimensional (3D) dose distribution for stereotactic treatment of spherical targets of 0.5 cm radius based on single beam two‐dimensional (2D) film dosimetry measurements. 1 cm target constitutes the worst case for the conformation with standard Multi‐Leaf Collimator (MLC) with 0.5 cm leaf width. The measured 2D transverse dose cross‐sections and the profiles in leaf and jaw directions were used to calculate radial dose distribution from isotropic beam arrangement, for both quadratic and circular beam openings, respectively. The results were compared for standard (100 cm) and reduced SAD 70 and 55 cm for different PI. Results: For practical reduction of SAD using quadratic openings, the improvement of healthy tissue sparing (HTS) at distances up to 3 times the PTV radius was at least 6%–12%; gradient indices (GI) were reduced by 3–39% for PI between 40% and 90%. Except for PI of 80% and 90%, quadratic apertures at SAD 70 cm improved the HTS by up to 20% compared to circular openings at 100 cm or were at least equivalent; GI were 3%–33% lower for reduced SAD in the PI range 40%–70%. For PI = 80% and 90% the results depend on the circular collimator model. Conclusion: Stereotactic treatments of spherical targets delivered at reduced SAD of 70 or 55 cm using MLC spare healthy tissue around the target at least as good as treatments at SAD 100 cm using circular collimators. The steeper beam penumbra at reduced SAD seems to be as important as perfect target conformity. The authors argue therefore that the beam penumbra width should be addressed in the stereotactic studies. KW - radiotherapy KW - stereotactic irradiation KW - penumbra KW - leaf width KW - virtual isocenter Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-177424 VL - 20 IS - 1 ER - TY - JOUR A1 - Beykan, Seval A1 - Fani, Melpomeni A1 - Jensen, Svend Borup A1 - Nicolas, Guillaume A1 - Wild, Damian A1 - Kaufmann, Jens A1 - Lassmann, Michael T1 - In vivo biokinetics of \(^{177}\)Lu-OPS201 in Mice and Pigs as a Model for Predicting Human Dosimetry JF - Contrast Media & Molecular Imaging N2 - Introduction. \(^{177}\)Lu-OPS201 is a high-affinity somatostatin receptor subtype 2 antagonist for PRRT in patients with neuroendocrine tumors. The aim is to find the optimal scaling for dosimetry and to compare the biokinetics of \(^{177}\)Lu-OPS201 in animals and humans. Methods. Data on biokinetics of \(^{177}\)Lu-OPS201 were analyzed in athymic nude Foxn1\(^{nu}\) mice (28 F, weight: 26 ± 1 g), Danish Landrace pigs (3 F-1 M, weight: 28 ± 2 kg), and patients (3 F-1 M, weight: 61 ± 17 kg) with administered activities of 0.19–0.27 MBq (mice), 97–113 MBq (pigs), and 850–1086 MBq (patients). After euthanizing mice (up to 168 h), the organ-specific activity contents (including blood) were measured. Multiple planar and SPECT/CT scans were performed until 250 h (pigs) and 72 h (patients) to quantify the uptake in the kidneys and liver. Blood samples were taken up to 23 h (patients) and 300 h (pigs). In pigs and patients, kidney protection was applied. Time-dependent uptake data sets were created for each species and organ/tissue. Biexponential fits were applied to compare the biokinetics in the kidneys, liver, and blood of each species. The time-integrated activity coefficients (TIACs) were calculated by using NUKFIT. To determine the optimal scaling, several methods (relative mass scaling, time scaling, combined mass and time scaling, and allometric scaling) were compared. Results. A fast blood clearance of the compound was observed in the first phase (<56 h) for all species. In comparison with patients, pigs showed higher liver retention. Based on the direct comparison of the TIACs, an underestimation in mice (liver and kidneys) and an overestimation in pigs’ kidneys compared to the patient data (kidney TIAC: mice = 1.4 h, pigs = 7.7 h, and patients = 5.8 h; liver TIAC: mice = 0.7 h, pigs = 4.1 h, and patients = 5.3 h) were observed. Most similar TIACs were obtained by applying time scaling (mice) and combined scaling (pigs) (kidney TIAC: mice = 3.9 h, pigs = 4.8 h, and patients = 5.8 h; liver TIAC: mice = 0.9 h, pigs = 4.7 h, and patients = 5.3 h). Conclusion. If the organ mass ratios between the species are high, the combined mass and time scaling method is optimal to minimize the interspecies differences. The analysis of the fit functions and the TIACs shows that pigs are better mimicking human biokinetics. KW - medicine KW - neuroendocrine tumors KW - biokinetics KW - \(^{177}\)Lu-OPS201 KW - dosimetry Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-177382 VL - 2019 ER - TY - JOUR A1 - Magyar, Attila A1 - Wagner, Martin A1 - Thomas, Phillip A1 - Malsch, Carolin A1 - Schneider, Reinhard A1 - Störk, Stefan A1 - Heuschmann, Peter U A1 - Leyh, Rainer G A1 - Oezkur, Mehmet T1 - HO-1 concentrations 24 hours after cardiac surgery are associated with the incidence of acute kidney injury: a prospective cohort study JF - International Journal of Nephrology and Renovascular Disease N2 - Background: Acute kidney injury (AKI) is a serious complication after cardiac surgery that is associated with increased mortality and morbidity. Heme oxygenase-1 (HO-1) is an enzyme synthesized in renal tubular cells as one of the most intense responses to oxidant stress linked with protective, anti-inflammatory properties. Yet, it is unknown if serum HO-1 induction following cardiac surgical procedure involving cardiopulmonary bypass (CPB) is associated with incidence and severity of AKI. Patients and methods: In the present study, we used data from a prospective cohort study of 150 adult cardiac surgical patients. HO-1 measurements were performed before, immediately after and 24 hours post-CPB. In univariate and multivariate analyses, the association between HO-1 and AKI was investigated. Results: AKI with an incidence of 23.3% (35 patients) was not associated with an early elevation of HO-1 after CPB in all patients (P=0.88), whereas patients suffering from AKI developed a second burst of HO-1 24 hours after CBP. In patients without AKI, the HO-1 concentrations dropped to baseline values (P=0.031). Furthermore, early HO-1 induction was associated with CPB time (P=0.046), while the ones 24 hours later lost this association (P=0.219). Conclusion: The association of the second HO-1 burst 24 hours after CBP might help to distinguish between the causality of AKI in patients undergoing CBP, thus helping to adapt patient stratification and management. KW - acute kidney injury KW - cardiac surgery KW - heme oxygenase-1 KW - cardiopulmonary bypass Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-177250 VL - 12 ER - TY - JOUR A1 - Jahn, Daniel A1 - Dorbath, Donata A1 - Kircher, Stefan A1 - Nier, Anika A1 - Bergheim, Ina A1 - Lenaerts, Kaatje A1 - Hermanns, Heike M. A1 - Geier, Andreas T1 - Beneficial effects of vitamin D treatment in an obese mouse model of non-alcoholic steatohepatitis JF - Nutrients N2 - Serum vitamin D levels negatively correlate with obesity and associated disorders such as non-alcoholic steatohepatitis (NASH). However, the mechanisms linking low vitamin D (VD) status to disease progression are not completely understood. In this study, we analyzed the effect of VD treatment on NASH in mice. C57BL6/J mice were fed a high-fat/high-sugar diet (HFSD) containing low amounts of VD for 16 weeks to induce obesity, NASH and liver fibrosis. The effects of preventive and interventional VD treatment were studied on the level of liver histology and hepatic/intestinal gene expression. Interestingly, preventive and to a lesser extent also interventional VD treatment resulted in improvements of liver histology. This included a significant decrease of steatosis, a trend towards lower non-alcoholic fatty liver disease (NAFLD) activity score and a slight non-significant decrease of fibrosis in the preventive treatment group. In line with these changes, preventive VD treatment reduced the hepatic expression of lipogenic, inflammatory and pro-fibrotic genes. Notably, these beneficial effects occurred in conjunction with a reduction of intestinal inflammation. Together, our observations suggest that timely initiation of VD supplementation (preventive vs. interventional) is a critical determinant of treatment outcome in NASH. In the applied animal model, the improvements of liver histology occurred in conjunction with reduced inflammation in the gut, suggesting a potential relevance of vitamin D as a therapeutic agent acting on the gut–liver axis. KW - vitamin D KW - obesity KW - NAFLD KW - NASH KW - inflammation KW - intestine KW - gut–liver axis Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-177222 VL - 11 IS - 1 ER -